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Li J, Zhang YJ, Zhao X, Yu Y, Xu JH, Hu R, Wu YH, Huang WQ, Wang ZX, Li TT. Impact of sodium butyrate on stroke-related intestinal injury in diabetic mice: Interference with Caspase-1/GSDMD pyroptosis pathway and preservation of intestinal barrier. Eur J Pharmacol 2025; 998:177455. [PMID: 40057153 DOI: 10.1016/j.ejphar.2025.177455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 02/27/2025] [Accepted: 03/04/2025] [Indexed: 03/20/2025]
Abstract
Diabetic stroke-associated acute intestinal injury is characterized by high mortality, disability, and poor prognosis due to the lack of effective therapies. Our prior research demonstrated that administration of 300 mg/kg sodium butyrate (NaB) can improve neurological outcomes post-diabetic stroke. Nonetheless, whether the effect of NaB is related to intestinal regulation, along with its underlying mechanisms, remains uncertain. This study aims to investigate the effects and mechanistic pathways of NaB on diabetic stroke-associated acute intestinal injury. A middle cerebral artery occlusion/reperfusion model was established in mice with streptozotocin-induced diabetes. The results demonstrated that NaB alleviated colonic injury 24 h after reperfusion in diabetic stroke. Pyroptosis-related protein levels in colonic tissues were significantly elevated following diabetic stroke but were markedly reduced with NaB treatment. NaB also improved gut barrier integrity and reduced inflammation, promoting epithelial barrier self-repair. In the NaB combined with lipopolysaccharide group, lipopolysaccharide administration induced a significant inflammatory response in the colonic tissue. Conversely, treatment with NaB and VX-765 (an inhibitor for Caspase-1) led to a notable alleviation in intestinal inflammation. These findings suggest that NaB mitigates colonic injury and enhances barrier function following diabetic stroke, potentially through the Caspase-1/Gasdermin D pyroptosis pathway. This study may provide a novel strategy and direction for intestinal rehabilitation in diabetic stroke patients.
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Affiliation(s)
- Jing Li
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yuan-Jia Zhang
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xu Zhao
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yu Yu
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jing-Hong Xu
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Rong Hu
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ye-Hui Wu
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wen-Qi Huang
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
| | - Zhong-Xing Wang
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
| | - Ting-Ting Li
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
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2
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Wu J, Li Z, Zhao J, Zhang T, Zhang J, Lv Q, Li J, Wang G, Han J, Zou Z. Atypical sulfur-containing physalin from Physalis minima and protective effect against ischemia-reperfusion injury. PHYTOCHEMISTRY 2025; 235:114478. [PMID: 40086499 DOI: 10.1016/j.phytochem.2025.114478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 03/10/2025] [Accepted: 03/11/2025] [Indexed: 03/16/2025]
Abstract
Four previously undescribed physalins (1-4), along with six known ones (5-10) were isolated and identified from the whole plants of Physalis minima L., a medicinal and edible plant traditionally used in southwest China. Their structures were established through comprehensive spectroscopic analyses, including high-resolution electrospray ionization mass spectrometry and 1D/2D nuclear magnetic resonance spectroscopy. Moreover, the absolute configurations of 1-3, 5 and 7 were examined by X-ray diffraction analyses. Compound 1, an undescribed sulfur-containing physalin, exhibited the most protective effect against oxygen-glucose deprivation/reperfusion (OGD/R)-stimulated ischemia-reperfusion (I/R) injury in PC12 cells. Meanwhile, compound 1 was found to reduce the inflammatory response, with mechanistic studies indicating that it decreased pyroptosis-associated proteins, such as cleaved-caspase1, NLRP3, and GSDMD N-terminus. Importantly, GSDMD knockdown significantly reversed the protective effects of compound 1, highlighting the involvement of pyroptosis in the compound's protective mechanism against OGD/R-induced I/R injury in PC12 cells in vitro.
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Affiliation(s)
- Jiangping Wu
- Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Anhui Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui, Anhui Innovative Center for Drug Basic Research of Metabolic Diseases, Wannan Medical College, Wuhu, 241002, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China
| | - Zixu Li
- Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Anhui Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui, Anhui Innovative Center for Drug Basic Research of Metabolic Diseases, Wannan Medical College, Wuhu, 241002, China
| | - Jianping Zhao
- National Center for Natural Products Research, School of Pharmacy, University of Mississippi, MS, 38677, USA
| | - Tao Zhang
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China
| | - Jun Zhang
- Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Anhui Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui, Anhui Innovative Center for Drug Basic Research of Metabolic Diseases, Wannan Medical College, Wuhu, 241002, China
| | - Qiuyue Lv
- Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Anhui Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui, Anhui Innovative Center for Drug Basic Research of Metabolic Diseases, Wannan Medical College, Wuhu, 241002, China
| | - Jiangfei Li
- Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Anhui Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui, Anhui Innovative Center for Drug Basic Research of Metabolic Diseases, Wannan Medical College, Wuhu, 241002, China
| | - Guodong Wang
- Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Anhui Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui, Anhui Innovative Center for Drug Basic Research of Metabolic Diseases, Wannan Medical College, Wuhu, 241002, China
| | - Jun Han
- Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Anhui Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui, Anhui Innovative Center for Drug Basic Research of Metabolic Diseases, Wannan Medical College, Wuhu, 241002, China; Wuhu Modern Technology Research and Development Center of Chinese herbal Medicines and Functional Foods, Anhui College of Traditional Chinese Medicine, Wuhu, 241002, China.
| | - Zhongmei Zou
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China.
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3
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Liu Y, Mao X, Li Q, Liu Y, Wu X, Chu M, Niu H, Sun L, He Y, Chang X, Guo D, Shi M, Zhang Y, Zhao J, Zhu Z. Increased serum total bile acid level is associated with improved prognosis of ischemic stroke. J Affect Disord 2025; 380:340-346. [PMID: 40147609 DOI: 10.1016/j.jad.2025.03.132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Revised: 03/20/2025] [Accepted: 03/22/2025] [Indexed: 03/29/2025]
Abstract
PURPOSE Bile acids are implicated in the cholesterol synthesis and lipid metabolism. We aimed to prospectively investigate the relationships between serum TBA and adverse clinical outcomes after ischemic stroke. METHODS Serum TBA levels at baseline were measured for 6609 ischemic stroke patients admitted at Minhang Hospital from January 2018 to December 2022. The primary outcome was a composite outcome of death and major disability (modified Rankin Scale [mRS] score, 3-6) at 3 months after stroke onset, and secondary outcomes included major disability (mRS score, 3-5), death (mRS score, 6), and ordered 7-level categorical score of the mRS. RESULTS During the 3-month follow-up period, a total of 2118 (34.5 %) patients experienced primary outcome. After multivariate adjustment, the odds ratios of primary outcome for the highest versus the lowest quartile of TBA were 0.71 (95 % CI, 0.58-0.88; Ptrend = 0.001). Each SD increase of log-transformed TBA was associated with a 12 % (95 % CI, 5 %-18 %) decreased risk of the primary outcome. Multiple-adjusted spline regression model showed a linear association of serum TBA levels with the primary outcome (P for linearity = 0.005). Subgroup analyses further confirmed the inverse associations between serum TBA levels and the prognosis of ischemic stroke. CONCLUSIONS Elevated serum TBA levels were independently associated with a decreased risk of adverse outcomes at 3 months after ischemic stroke, indicating that TBA might be implicated in the development of ischemic stroke and might be a prognostic biomarker for ischemic stroke.
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Affiliation(s)
- Yi Liu
- Department of Psychiatry, Affiliated Guangji Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China
| | - Xueyu Mao
- Department of Neurology, Minhang Hospital, Fudan University, Shanghai, China
| | - Qian Li
- Department of Neurology, Minhang Hospital, Fudan University, Shanghai, China
| | - Yang Liu
- Department of Neurology, Minhang Hospital, Fudan University, Shanghai, China; Institute of Science and Technology for Brain inspired Intelligence, Fudan University, Shanghai, China
| | - Xuechun Wu
- Department of Neurology, Minhang Hospital, Fudan University, Shanghai, China
| | - Min Chu
- Department of Neurology, Minhang Hospital, Fudan University, Shanghai, China
| | - Huicong Niu
- Department of Neurology, Minhang Hospital, Fudan University, Shanghai, China
| | - Lulu Sun
- Department of Psychiatry, Affiliated Guangji Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China
| | - Yu He
- Department of Psychiatry, Affiliated Guangji Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China
| | - Xinyue Chang
- Department of Psychiatry, Affiliated Guangji Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China
| | - Daoxia Guo
- School of Nursing, Suzhou Medical College of Soochow University, Suzhou, China
| | - Mengyao Shi
- Department of Psychiatry, Affiliated Guangji Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China
| | - Yonghong Zhang
- Department of Psychiatry, Affiliated Guangji Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China
| | - Jing Zhao
- Department of Neurology, Minhang Hospital, Fudan University, Shanghai, China; Institute of Healthy Yangtze River Delta, Shanghai Jiao Tong University, Shanghai, China.
| | - Zhengbao Zhu
- Department of Psychiatry, Affiliated Guangji Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China.
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4
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Zhu Y, Xue G, Xu S, Qin Q, Liu P, Ji L, Wu H, Wu M, Fang Z. U-Shaped Relationship of Serum Albumin and Neurological Functional Outcomes After Acute Ischemic Stroke: A Prospective Cohort Study. Neurol Ther 2025; 14:949-964. [PMID: 40237930 PMCID: PMC12089567 DOI: 10.1007/s40120-025-00729-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Accepted: 03/06/2025] [Indexed: 04/18/2025] Open
Abstract
INTRODUCTION Several studies indicate that individuals with acute ischemic stroke (AIS) who have low levels of serum albumin (SA) have a dismal prognosis. However, intravenously administering albumin 25% at a dose of 2 g/kg did not lead to improved outcomes for patients with AIS after 90 days. Our objective was to examine the possible correlation between SA levels and stroke outcomes in a prospective cohort investigation. METHODS The research included a total of 5111 participants diagnosed with AIS. The correlation between SA level and modified Rankin Scale (mRS) scores 90 days after onset was examined via univariate and multivariate logistic analyses. The relationships were examined employing restricted cubic splines. An investigation was conducted to ascertain the connection between SA levels and neurological functional results by employing mediation analysis, with the mediation impact of low-density lipoprotein (LDL) taken into account. In addition, the subgroup analyses were performed using the logistic regression. RESULTS The connection between levels of SA and neurological functional outcomes following AIS exhibited a U-shaped pattern. The likelihood of a negative result dropped significantly with an elevation in SA (per g/L: OR (odds ratio) 0.88; 95% CI (confidence interval) 0.847-0.913) among individuals with SA levels below 42.2 g/L. Conversely, the likelihood of a negative outcome rose with an increase in SA (per g/L: OR 1.033, 95% CI 1.009-1.058) among people with SA levels of 42.2 g/L or above. Comparable findings were seen for mortality outcomes. A mediation study revealed that LDL had a mediating function in the statistical connection between SA levels and neurological functional outcomes, accounting for 12.3% of the connection. No significant interactions were seen in any of the groupings. CONCLUSION Among patients with AIS, there was a U-shaped relationship between SA levels at admission and the likelihood of poor outcomes, which was partially mediated by LDL. There is a Graphical Abstract available for this article.
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Affiliation(s)
- Yuan Zhu
- Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
- Department of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, University of California Irvine (UCI), California, Irvine, USA
| | - Gang Xue
- Yangzhou Hospital of Traditional Chinese Medicine, Yangzhou, China
| | - Shufan Xu
- Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Qi Qin
- Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Peian Liu
- Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Lianhong Ji
- Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Huimin Wu
- Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Minghua Wu
- Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
| | - Zhuyuan Fang
- Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
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5
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Zhang Y, Yang S, Wang S, Zou X, Tang L, Chen L, Ma J, Li Y, Yao T, Zhang X, Tang R, Tang L, Zhang F, Zhou H, Xu L, Tang Q, Ma S, Yi Y, Liu R, Bai G, Zeng Y, Zhou Y, Zhao Y, Wang Y, Yang Q, Wang D, Shen M, Zhang L. Prevalence and 10-Year Risk of Intracerebral Hemorrhage in Central China Using Estimates From the 1 Million Cross-Sectional Study. Neurology 2025; 104:e213545. [PMID: 40258204 DOI: 10.1212/wnl.0000000000213545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 02/11/2025] [Indexed: 04/23/2025] Open
Abstract
BACKGROUND AND OBJECTIVES Intracerebral hemorrhage (ICH) is a common and fatal type of stroke, especially in central China. However, recent epidemiologic data are scarce. The study aimed to investigate the latest prevalence of ICH in central China and assess the risk of ICH in the next 10 years based on the Resident Health Records (RHR) data. METHODS First, this cross-sectional study was based on a large-scale face-to-face investigation of ICH, which was launched on residents aged 20 years or older from January 1, 2021, to December 31, 2021, and estimated the prevalence of ICH in Hunan, a representative province in central China. Then, based on the RHR database, we assessed the ICH risk, population attributable fraction (PAF), and effects of ICH prevention under different risk factor control scenarios over the next decade by the China Kadoorie Biobank (CKB)-cardiovascular disease (CVD) model. RESULTS In 2021, 1.78 million participants enrolled in the investigation (mean age = 50.1 years; 51% male). The age-standardized prevalence rate of ICH was 159.2 (95% CI 153.7-164.9) per 100,000. The prevalence rate of ICH in men was 193.6 (95% CI 185.2-202.5) per 100,000, while in women was 124.0 (95% CI 117.1-131.3) per 100,000, and it increased with age. Spatial aggregation was observed, with the peak prevalence rate of ICH at 327.3 (95% CI 293.1-365.5) per 100,000 in Zhuzhou, followed by Changsha was 215.8 (95% CI 190.6-243.9) per 100,000, while Shaoyang had the lowest rate was 62.8 (95% CI 51.2-77.1) per 100,000. For the assessment of 10-year ICH risk, we included a total of 8.36 million participants aged 30-79 with the RHR database into the CKB-CVD model. We found that there will be 354,146 cases (ICH risk: 4.2%) of ICH among the participants in the next decade. Controlling hypertension showed the highest potential for ICH prevention, with a PAF of 8.6%. By controlling hypertension, smoking, waist circumference, and diabetes, 56,673 ICH cases (PAF 19.1%) can be avoided in the next decade. DISCUSSION The ICH prevalence in central China remained high. Strict blood pressure control could significantly reduce the risk of ICH in the next 10 years. It is important to continually improve ICH prevention strategies in the general population.
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Affiliation(s)
- Yupeng Zhang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Songchun Yang
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
| | - Sai Wang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Xuelun Zou
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Li Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Lei Chen
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Junyi Ma
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Ye Li
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Tianxing Yao
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Xiangbin Zhang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Rongmei Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Lei Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Feng Zhang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Hunan, Changsha, China
| | - Huifang Zhou
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Lianxu Xu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Qiaoling Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Siyuan Ma
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Yexiang Yi
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Ran Liu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Genghuai Bai
- School of Computer Science and Engineering, Central South University, Changsha, Hunan, China
| | - Yi Zeng
- Department of Geriatrics, Second Xiangya Hospital, Central South University, Changsha, China
| | - Yanhong Zhou
- Cancer Research Institute, Basic School of Medicine, Central South University, Changsha, Hunan, China
| | - Ying Zhao
- School of Computer Science and Engineering, Central South University, Changsha, Hunan, China
| | - Yang Wang
- Institute of Integrative Chinese Medicine, Department of Integrated Chinese Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Qidong Yang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Duolao Wang
- Department of Clinical Sciences, Liverpool School of Tropical Medicine, United Kingdom
| | - Minxue Shen
- Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, China
| | - Le Zhang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, China; and
- FuRong Laboratory, Changsha, Hunan, China
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6
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Luo C, Tang X, Shao H, Guo F. High-frequency repetitive transcranial magnetic stimulation attenuates white matter damage and improves functional recovery in rats with ischemic stroke. Neuroscience 2025; 575:48-56. [PMID: 40239890 DOI: 10.1016/j.neuroscience.2025.04.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 03/25/2025] [Accepted: 04/12/2025] [Indexed: 04/18/2025]
Abstract
Stroke is a major cause of acquired disability and the second most frequent cause of dementia, while specific therapeutic rehabilitation strategies remain limited. Repetitive transcranial magnetic stimulation(rTMS) is a well-known rehabilitation modality after cerebral ischemic injury. White matter damage is an important contributor to motor and cognitive dysfunctions after stroke. This study aimed to evaluate the effect of rTMS on white matter recovery and neurological deficits in ischemic stroke. Grip strength test and novel object recognition test were conducted to assess motor and cognitive functions after middle cerebral artery occlusion(MCAO). MRI, including Diffusion tensor imaging (DTI) and Diffusion Tensor Tractography (DTT) were performed to evaluate white matter injury in MCAO rats. Moreover, Western blotting were detected to observe related myelin damage proteins in the ischemic brain. The results revealed that 10 Hz rTMS alleviated the motor and cognitive deficits in rats after ischemic surgery. Besides, the data from DTI and DTT showing that 10 Hz rTMS ameliorated the white matter lesion of rats after cerebral ischemia. In addition, 10 Hz rTMS attenuated significant loss of the myelin sheath by enhanced myelin associated proteins levels in the ischemic brain of ischemic rats. These findings suggest that 10 Hz rTMS exerted therapeutic neuroprotective properties after ischemic stroke, in a manner that may be associated with enhancing structural repairment of the white matter, which may provide a potential therapeutic strategy for ischemic stroke.
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Affiliation(s)
- Can Luo
- Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiangyu Tang
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Haoyue Shao
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Feng Guo
- Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Wang D, Zhang Z, Zhang Y, Chen S, Qu N, Li H, Sun Y, Tian X, Han X, Wu S, Wang A. Two-Year Changes in Remnant Cholesterol and Stroke Risk in the Chinese Population: A Prospective Cohort Study. J Am Heart Assoc 2025:e038559. [PMID: 40401619 DOI: 10.1161/jaha.124.038559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 04/25/2025] [Indexed: 05/23/2025]
Abstract
BACKGROUND Previous studies have shown that elevated remnant cholesterol (RC) was associated with stroke risk. There is insufficient evidence on the relationship between 2-year changes in RC and stroke risk in the general population. Our aim was to explore the relationship between 2-year changes in RC and the risks of stroke and its subtypes in the general population. METHODS The study included 62 443 individuals who were free of stroke from the Kailuan Study. Two-year changes in RC was defined as the difference between the RC in 2008 and that in 2006. Multivariable-adjusted Cox proportion models were used to examine the associations between 2-year changes in RC with the risks of stroke and its subtypes. RESULTS During a median follow-up period of 10.30 years, 3780 (6.38%) stroke events occurred. The changes in RC were positively associated with the risk of stroke, after adjustment for multiple potential confounders. The hazard ratio (HR) for the Q4 group versus the Q1 group was 1.14 (95%, CI, 1.02-1.28) for stroke, and 1.18 (95% CI, 1.04-1.32) for ischemic stroke. The risks of stroke were higher in the RC increased group than the RC nonincreased group. The HR was 1.12 (95% CI, 1.04-1.20) for stroke, and 1.15 (95% CI, 1.07-1.24) for ischemic stroke. CONCLUSIONS Substantial changes in RC are associated with increased risks of stroke in the general population. Monitoring long-term changes in RC may assist with the early identification of individuals at high risk of stroke.
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Affiliation(s)
- Dan Wang
- Encephalopathy Center The First Affiliated Hospital of Henan University of Chinese Medicine Zhengzhou China
| | - Zifei Zhang
- Department of Neurology Kaifeng Central Hospital, Xinxiang Medical University Kaifeng China
| | - Yijun Zhang
- Department of Epidemiology Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University Beijing China
- China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital, Capital Medical University Beijing China
- Department of Clinical Epidemiology and Clinical Trial Capital Medical University Beijing China
| | - Shuohua Chen
- Department of Cardiology Kailuan Hospital, North China University of Science and Technology Tangshan China
| | - Nan Qu
- Encephalopathy Center The First Affiliated Hospital of Henan University of Chinese Medicine Zhengzhou China
| | - Haibin Li
- Department of Cardiac Surgery, Heart Center and Beijing Key Laboratory of Hypertension Beijing Chaoyang Hospital, Capital Medical University Beijing China
| | - Yongkang Sun
- Encephalopathy Center The First Affiliated Hospital of Henan University of Chinese Medicine Zhengzhou China
| | - Xue Tian
- Department of Epidemiology Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University Beijing China
- China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital, Capital Medical University Beijing China
- Department of Clinical Epidemiology and Clinical Trial Capital Medical University Beijing China
| | - Xinsheng Han
- Department of Neurology Kaifeng Central Hospital, Xinxiang Medical University Kaifeng China
- Henan Key Laboratory of Neuromuscular Pathology Kaifeng Central Hospital Kaifeng China
| | - Shouling Wu
- Department of Cardiology Kailuan Hospital, North China University of Science and Technology Tangshan China
| | - Anxin Wang
- Department of Epidemiology Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University Beijing China
- China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital, Capital Medical University Beijing China
- Department of Clinical Epidemiology and Clinical Trial Capital Medical University Beijing China
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Yu Q, Liu Y, Chang X, Mao X, Wu X, Chu M, Niu H, Shi M, Sun L, He Y, Liu Y, Guo D, Zhu Z, Zhao J. High-Normal Serum Potassium, Calcium, and Magnesium Levels Are Associated With Decreased Risks of Adverse Outcomes After Ischemic Stroke. J Am Heart Assoc 2025; 14:e037601. [PMID: 40357677 DOI: 10.1161/jaha.124.037601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 04/08/2025] [Indexed: 05/15/2025]
Abstract
BACKGROUND High serum potassium, calcium, and magnesium levels have been reported to be associated with decreased risks of ischemic stroke, whereas their prognostic values in ischemic stroke remain unclear. We aimed to prospectively explore the associations of serum potassium, calcium, and magnesium levels with the prognosis of ischemic stroke. METHODS We measured serum potassium, calcium, and magnesium levels at baseline among 5469 patients with ischemic stroke from the Minhang Stroke Cohort study. The primary outcome was the composite outcome of death and major disability (modified Rankin Scale score ≥3) at 3 months after ischemic stroke. Secondary outcomes included major disability, death, and the ordered 7-level categorical score of the modified Rankin Scale. RESULTS During 3-month follow-up, 1834 patients developed the primary outcome. After multivariate adjustment, the adjusted odds ratios of primary outcome for the highest versus the lowest quartile were 0.79 (95% CI, 0.68-0.93; Ptrend=0.007) for potassium, 0.69 (95% CI, 0.58-0.82; Ptrend<0.001) for calcium, and 0.83 (95% CI, 0.70-0.99; Ptrend=0.015) for magnesium. Multivariable-adjusted restricted cubic spline analyses showed linear dose-response relationships of serum potassium, calcium, and magnesium with the risk of primary outcome (all P for linearity<0.05). CONCLUSIONS High-normal serum potassium, calcium, and magnesium levels were associated with decreased risks of adverse outcomes at 3 months after ischemic stroke, suggesting that serum potassium, calcium, and magnesium might be valuable prognostic biomarkers for ischemic stroke.
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Affiliation(s)
- Quan Yu
- Department of Psychiatry Affiliated Guangji Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University Suzhou China
| | - Yang Liu
- Department of Neurology, Minhang Hospital Fudan University Shanghai China
- Institute of Science and Technology for Brain Inspired Intelligence Fudan University Shanghai China
| | - Xinyue Chang
- Department of Psychiatry Affiliated Guangji Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University Suzhou China
| | - Xueyu Mao
- Department of Neurology, Minhang Hospital Fudan University Shanghai China
| | - Xuechun Wu
- Department of Neurology, Minhang Hospital Fudan University Shanghai China
| | - Min Chu
- Department of Neurology, Minhang Hospital Fudan University Shanghai China
| | - Huicong Niu
- Department of Neurology, Minhang Hospital Fudan University Shanghai China
| | - Mengyao Shi
- Department of Psychiatry Affiliated Guangji Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University Suzhou China
| | - Lulu Sun
- Department of Psychiatry Affiliated Guangji Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University Suzhou China
| | - Yu He
- Department of Psychiatry Affiliated Guangji Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University Suzhou China
| | - Yi Liu
- Department of Psychiatry Affiliated Guangji Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University Suzhou China
| | - Daoxia Guo
- School of Nursing Suzhou Medical College of Soochow University Suzhou China
| | - Zhengbao Zhu
- Department of Psychiatry Affiliated Guangji Hospital of Soochow University, School of Public Health, Suzhou Medical College of Soochow University Suzhou China
| | - Jing Zhao
- Department of Neurology, Minhang Hospital Fudan University Shanghai China
- Institute of Healthy Yangtze River Delta Shanghai Jiao Tong University Shanghai China
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Wang ZY, Bao H, Zhang QB. Combining Computed Tomography Angiography and Computed Tomography Perfusion for Evaluating Patients With Middle Cerebral Artery Stenosis and Acute Cerebral Infarction. J Craniofac Surg 2025:00001665-990000000-02733. [PMID: 40377925 DOI: 10.1097/scs.0000000000011502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2025] [Accepted: 04/13/2025] [Indexed: 05/18/2025] Open
Abstract
OBJECTIVE Investigate the correlation between MCA stenosis severity and CTP parameter changes in ACI patients. MATERIALS AND METHODS Sixty unilateral MCA stenosis-induced ACI patients (6 h-7 d post-onset) underwent CTA+CTP. Patients were stratified by stenosis degree: mild (<50%), moderate (50%-69%), severe (≥70%). CTP parameters were compared across groups. Patients with 50% to 100% stenosis were further analyzed by collateral circulation status (scores 2-3: good; 0-1: poor). Differences in CTP parameters and 90-day mRS were evaluated. RESULTS (1) Good collateral circulation (scores 2-3) was associated with higher CBF/CBV, prolonged TTP/MTT, and lower NIHSS/90-day mRS compared with poor circulation (scores 0-1). (2) Mild stenosis showed increased CBF/CBV in unaffected hemisphere. Moderate stenosis demonstrated reduced CBV and prolonged TTP/MTT in affected hemisphere. Severe stenosis exhibited increased CBF/CBV in unaffected hemisphere. CONCLUSION (1) CBV and CBF reduction positively correlated with stenosis severity. (2) Adequate collateral circulation was associated with reduced early neurological damage and disability.
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Affiliation(s)
- Ze-Ying Wang
- Department of Neurology, Hulunbuir People's Hospital
| | - Hua Bao
- Department of Encephalopathy, Hulunbuir Mongolian Medical Hospital
| | - Qin-Bao Zhang
- Department of Cardiology, Hulunbuir People's Hospital, Hulunbuir, Inner Mongolia Autonomous Region, China
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Qian N, Lu C, Wei T, Yang W, Wang H, Chen H, Li J, Zhu S, Wang W, Shao N. Epidemiological trends and forecasts in stroke at global, regional and national levels. J Stroke Cerebrovasc Dis 2025; 34:108347. [PMID: 40381865 DOI: 10.1016/j.jstrokecerebrovasdis.2025.108347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2025] [Revised: 05/09/2025] [Accepted: 05/12/2025] [Indexed: 05/20/2025] Open
Abstract
BACKGROUND Stroke, characterized as ischemic or hemorrhagic, leads to severe morbidity, mortality, and recurrence. This research analyzed stroke epidemiological trends from 1990-2021. METHODS The Global Burden of Disease database provided stroke data including incidence, mortality, and disability-adjusted life-years (DALYs). Age-standardized rates (ASRs) and Estimated Annual Percent Changes (EAPC) measured incidence and mortality shifts. The sociodemographic index (SDI) was explored alongside stroke burden. Forecasting of stroke trends until 2035 utilized the Bayesian age-period-cohort (BAPC) model. The factors influencing the variability of stroke burden were subjected to decomposition analysis for a more in-depth examination. Additionally, frontier analysis was employed to visually illustrate the opportunities for alleviating burden in each nation or region, taking into account their respective stages of development.This study utilized the slope index of inequality (SII) and the concentration index, as defined by the World Health Organization (WHO), to assess absolute and relative inequalities in disease burden. RESULTS From 1990-2021, global stroke incidence increased by 15.03 %, with an overall decline in age-standardized incidence rate (ASIR). Lower in females than males, the incidence rise was larger in females. Stroke mortality declined by 2.60 % overall, with a rise in male mortality and decrease in female mortality. DALYs increased, with a 10.67 % decline by rate per 100,000 people. Eastern Europe, Central Asia, and East Asia experienced the highest incidence rates, with the greatest ASIR decline in the high-income Asia Pacific region. The decomposition analysis revealed a notable rise in Disability-Adjusted Life Years (DALYs) within the middle Socio-Demographic Index (SDI) quintile region, where factors such as aging and population growth were identified as primary contributing elements. Additionally, the frontier analysis indicated that nations or regions categorized within higher SDI quintiles are likely to exhibit greater potential for improvement. Projections for 2035 anticipate increased stroke cases alongside further ASIR and ASMR declines. Cross-country inequality analysis suggests that both absolute and relative health inequalities associated with the stroke burden have escalated during the period from 1990 to 2021. CONCLUSION Despite rising global stroke incidence and DALYs, decreases were seen in ASIR and ASMR since 1990. Incidence rates increased most quickly in females, with regional variation observable. High systolic blood pressure remained a key risk factor. Future efforts should target prevention and treatment to mitigate sex, age, and regional stroke disparities.
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Affiliation(s)
- Nannan Qian
- Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, China; Anhui University of Chinese Medicine First Clinical Medical College, Hefei, Anhui 230031, China; Key Laboratory of Xin'An Medicine, Ministry of Education, Hefei, Anhui 230031, China; Graduate School, Anhui University of Chinese Medicine, Hefei, Anhui 230031, China.
| | - Chengcheng Lu
- Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, China; Clinical College of Anhui Medical University, Hefei, Anhui 230031, China.
| | - Taohua Wei
- Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, China; Anhui University of Chinese Medicine First Clinical Medical College, Hefei, Anhui 230031, China; Key Laboratory of Xin'An Medicine, Ministry of Education, Hefei, Anhui 230031, China; Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine, Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, Anhui 230031, China.
| | - Wenming Yang
- Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, China; Anhui University of Chinese Medicine First Clinical Medical College, Hefei, Anhui 230031, China; Key Laboratory of Xin'An Medicine, Ministry of Education, Hefei, Anhui 230031, China; Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine, Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, Anhui 230031, China.
| | - Han Wang
- Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, China; Anhui University of Chinese Medicine First Clinical Medical College, Hefei, Anhui 230031, China; Key Laboratory of Xin'An Medicine, Ministry of Education, Hefei, Anhui 230031, China; Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine, Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, Anhui 230031, China; Graduate School, Anhui University of Chinese Medicine, Hefei, Anhui 230031, China.
| | - Huaizhen Chen
- Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, China; Anhui University of Chinese Medicine First Clinical Medical College, Hefei, Anhui 230031, China; Key Laboratory of Xin'An Medicine, Ministry of Education, Hefei, Anhui 230031, China; Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine, Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, Anhui 230031, China.
| | - Jun Li
- Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, China; Anhui University of Chinese Medicine First Clinical Medical College, Hefei, Anhui 230031, China.
| | - Sihuan Zhu
- Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, China; Anhui University of Chinese Medicine First Clinical Medical College, Hefei, Anhui 230031, China; Key Laboratory of Xin'An Medicine, Ministry of Education, Hefei, Anhui 230031, China; Graduate School, Anhui University of Chinese Medicine, Hefei, Anhui 230031, China.
| | - Weiqi Wang
- Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, China; Anhui University of Chinese Medicine First Clinical Medical College, Hefei, Anhui 230031, China; Key Laboratory of Xin'An Medicine, Ministry of Education, Hefei, Anhui 230031, China; Graduate School, Anhui University of Chinese Medicine, Hefei, Anhui 230031, China.
| | - Ningshu Shao
- Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, China; Anhui University of Chinese Medicine First Clinical Medical College, Hefei, Anhui 230031, China; Key Laboratory of Xin'An Medicine, Ministry of Education, Hefei, Anhui 230031, China; Graduate School, Anhui University of Chinese Medicine, Hefei, Anhui 230031, China.
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Lyu J, Liu F, Chai Y, Wang X, Liu Y, Xie Y. Identification of causal plasma metabolite biomarkers for ischemic stroke using Mendelian randomization and mediation analysis. Sci Rep 2025; 15:16789. [PMID: 40369036 PMCID: PMC12078489 DOI: 10.1038/s41598-025-01329-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Accepted: 05/05/2025] [Indexed: 05/16/2025] Open
Abstract
The Global Burden of Disease Study 2021 reports that stroke remains a leading cause of death, with ischemic stroke (IS) presenting significant challenges in screening, prevention, and treatment. We explored the causal effects of 1,400 plasma metabolites on IS outcomes using a two-sample Mendelian randomization (MR) framework. We assessed causal relationships between IS and 11 common clinical risk factors and further examined these relationships for metabolites. Mediation analysis identified mechanisms for metabolites affecting both IS and its risk factors. Finally, a phenome-wide association study (PheWAS) MR analysis evaluated the side effects and additional indications of IS-associated metabolites across 3,948 phenotypes from the UKBB GWAS. Nineteen metabolites showed a causal relationship with IS. MR analysis confirmed body mass index (BMI), high-density lipoprotein (HDL), systolic blood pressure (SBP), diastolic blood pressure (DBP), and type 2 diabetes (T2D) as risk factors for IS. Among 136 metabolites associated with at least one IS risk factor, 132 were linked to risk factors but not directly to IS. BMI, DBP, and coffee intake mediated the causal relationship between IS and the levels of 1-stearoyl-GPG (18:0), 1-oleoyl-2-linoleoyl-GPE (18:1/18:2), Octadecadienedioate (C18:2-DC), and X-24,951. Phe-MR analysis indicated that these metabolites were protective and affected other indications similarly to IS. Our findings reveal causal pathways and identify four potential biomarkers for IS, providing new insights for its screening, prevention, and treatment.
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Affiliation(s)
- Jian Lyu
- NMPA Key Laboratory for Clinical Research and Evaluation of Traditional Chinese Medicine & National Clinical Research Center for Chinese Medicine Cardiology, XiYuan Hospital, China Academy of Chinese Medical Sciences, No.1 Xiyuan playground Road, Haidian District, Beijing, 100091, PR China.
| | - Fumei Liu
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, No.16 Nanxiaojie, Inner Dongzhimen, Dongcheng District, Beijing, 100700, PR China
| | - Yan Chai
- Department of Epidemiology, University of California, 405 Hilgard Avenue, Los Angeles, 90095, CA, USA
| | - Xiting Wang
- Academy of Mathematics and Systems Science, Chinese Academy of Sciences, No. 55 Zhongguancun East Road, Beijing, 100190, China.
| | - Yi Liu
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, No.16 Nanxiaojie, Inner Dongzhimen, Dongcheng District, Beijing, 100700, PR China.
| | - Yanming Xie
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, No.16 Nanxiaojie, Inner Dongzhimen, Dongcheng District, Beijing, 100700, PR China.
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12
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Huang M, Wang W, Li WL, Chen YQ, Chen XT, Liu Y, Li Y, Ren DM, Wang F. Construction and evaluation of a nomogram model for predicting the risk of hospital-acquired pneumonia in elderly patients with acute ischemic stroke. BMC Geriatr 2025; 25:340. [PMID: 40369418 PMCID: PMC12080133 DOI: 10.1186/s12877-025-05936-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Accepted: 04/10/2025] [Indexed: 05/15/2025] Open
Abstract
OBJECTIVE In this study, we aimed to develop and validate an easy-to-use model to predict the risk of hospital-acquired pneumonia (HAP) in elderly patients with acute ischemic stroke (AIS). METHODS A total of 2861 elderly AIS patients who were admitted to Jiading District Central Hospital Affiliated with Shanghai University of Medicine & Health Science from January 2016 to December 2023 were selected. Among these patients, 699 were diagnosed with HAP (HAP group), and 2162 patients were included in the control group (non-HAP group). Univariate and multivariate logistic regression analyses were performed to determine the risk factors for HAP after AIS. These factors were then used to establish a scoring system, from which a nomogram model was developed with R software. RESULTS Univariate analysis revealed 17 factors that were significantly associated with the development of HAP after AIS in elderly patients (P < 0.05). Multivariate logistic regression analysis including these factors revealed that age, the national institute of health stroke scale (NIHSS) score within 24 h of admission (Kwah LK. J Physiother 60:61, 2014), the stress hyperglycemia ratio (SHR), smoking status, and dysphagia status were independent risk factors for HAP after AIS. According to the oxfordshire community stroke project (OCSP) classification, patients classified as having the total anterior circulation infarct (TACI), partial anterior circulation infarct (PACI), and posterior circulation infarct (POCI) sub-types had a significantly increased risk of HAP compared with those classified as having the lacunar infarct (LACI) sub-type. A nomogram model constructed from these six risk factors yielded a C-index of 0.834 (95% confidence interval (CI): 0.811-0.857), indicating high accuracy. Calibration and clinical decision curve analyses revealed the reliability and clinical value of the proposed model. CONCLUSION Our proposed nomogram provides clinicians with a simple and reliable tool for predicting HAP from conventional data. The model can also help clinicians make personalized treatment decisions for patients at different risk levels. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Man Huang
- Department of Nursing, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Wan Wang
- Department of Neurology, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Wu-Lin Li
- Shanghai Key Laboratory of Molecular Imaging, Department of Emergency and Critical Care Medicine, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Yan-Qing Chen
- Department of Nursing, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Xian-Ting Chen
- Shanghai Key Laboratory of Molecular Imaging, Department of Emergency and Critical Care Medicine, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Ye Liu
- Department of Neurology, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Yan Li
- Department of Nursing, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Dong-Mei Ren
- Department of Nursing, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China.
- Department of Nursing, No.111, No.1, Chengbei Rd, Jiading District, Shanghai, China.
| | - Fei Wang
- Shanghai Key Laboratory of Molecular Imaging, Department of Emergency and Critical Care Medicine, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China.
- Department of Emergency and Critical Care Medicine, No.1, Chengbei Rd, Jiading District, Shanghai, China.
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Zeng J, Zhou H, Wan H, Yang J. Single-cell omics: moving towards a new era in ischemic stroke research. Eur J Pharmacol 2025; 1000:177725. [PMID: 40350018 DOI: 10.1016/j.ejphar.2025.177725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 05/08/2025] [Accepted: 05/09/2025] [Indexed: 05/14/2025]
Abstract
Ischemic stroke (IS) is a highly complex and heterogeneous disease involving multiple pathophysiological events. A better understanding of the pathophysiology of IS will enhance preventive, diagnostic and therapeutic strategies. Despite significant advances in modern medicine, the molecular mechanisms of IS are still largely unknown. The high-throughput omics approach opens new avenues for identifying IS biomarkers and elucidating disease pathogenesis mechanisms. Single-cell omics enables a more thorough and in-depth analysis of the cellular interactions and properties in IS. This will lead to a better understanding of the onset, treatment and prognosis of IS. In this paper, we first reviewed the disease signatures and mechanisms research of IS. Subsequently, the use of single-cell omics to comprehend the mechanisms of IS was discussed, along with some recent developments in the field. To further delineate the upstream pathogenic alterations and downstream molecular impacts of IS, we also discussed the current use of machine learning approaches to single-cell omics data analysis. Particularly, single-cell omics is being used to inform risk assessment, early patient diagnosis and treatment strategies, and their potential impact on precision medicine. Thus, we summarized the role of single-cell omics in precision medicine. Despite the relative youth of the field, the development of single-cell omics promises to provide a powerful tool for elucidating the pathogenesis of IS.
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Affiliation(s)
- Jieqiong Zeng
- School of Basic Medicine Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China; School of Ecological and Environmental, Hubei Industrial Polytechnic, Shiyan, 442000, China
| | - Huifen Zhou
- School of Basic Medicine Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Haitong Wan
- School of Basic Medicine Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
| | - Jiehong Yang
- School of Basic Medicine Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
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14
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Khraiwesh A, Ikhdour O, Alalyat Z, Damiri B, Abuhassan A, Abuawad M. A retrospective study on sex disparities and risk factors in acute ischemic stroke in the West bank of Palestine. Sci Rep 2025; 15:16135. [PMID: 40341166 PMCID: PMC12062429 DOI: 10.1038/s41598-025-01268-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Accepted: 05/05/2025] [Indexed: 05/10/2025] Open
Abstract
Acute ischemic stroke (AIS) is one of the leading causes of mortality and morbidity. This study aimed to identify risk factors, subtypes, and associated outcomes of AIS in the West Bank based on sex. We retrospectively analyzed medical records from 2018 to 2022 of stroke patients from four main hospitals in the West Bank (N = 711). The Modified Rankin Scale (mRS) assessed post-stroke disability on presentation day and thirty days later based on patient history and physical examination findings. An adjusted multinomial logistic regression model was implemented to calculate the adjusted odds ratios (OR) and the 95% confidence interval (CI). The significance level was set at P < 0.05. Out of 711 records, 118 were excluded. The final analysis included 593 AIS patients, with a median age of 63 and an interquartile range of 15. The majority of the patients (60.37%) were males and most of them (62.1%) were smokers. Males were less likely to have diabetes mellitus (DM) (P = 0.037, OR = 0.691) and atrial fibrillation (P = 0.039, OR = 0.627) compared to females. Small-volume strokes accounted for the majority of cases (60.7%). AIS had a thrombotic cause in (81.9%) of patients. On presentation, (40.4%) and (37.2%) of patients had more severe symptoms with mRS scores of 4 and 3, respectively. Males were more likely than females (P = 0.018, OR = 2.03) to present with more severe symptoms (mRS 3-4-5) on day one. An increase of one year in age resulted in a 9.8% higher risk of death (mRS 6) on day one (P = 0.016, OR = 1.098). Smoking history was associated with a seven-fold increase in mortality on day one (P = 0.049, OR = 7.396). Males developed AIS at a younger age while DM and atrial fibrillation were significantly more common in females. The majority of patients reported more severe symptoms on presentation, with notable differences observed between sexes. Male patients exhibited a higher prevalence of severe symptoms compared to female patients. Additionally, key risk factors such as smoking was significantly associated with the severity of symptoms at presentation, with variations observed across sexes. Prevention of risk factors (e.g., HTN, DM, atrial fibrillation, and smoking) is crucial, and further research is required.
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Affiliation(s)
- Ahmed Khraiwesh
- Department of Medicine, An-Najah National University, Nablus, Palestine
| | - Osama Ikhdour
- Department of Medicine, An-Najah National University, Nablus, Palestine
| | - Zainab Alalyat
- Department of Medicine, An-Najah National University, Nablus, Palestine
| | - Basma Damiri
- Drugs and Toxicology Division, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
| | - Ahmad Abuhassan
- An-Najah National University Hospital, An-Najah National University, Nablus, Palestine
| | - Mohammad Abuawad
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine.
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Huo G, Yao Z, Yang X, Wu G, Chen L, Zhou D. Association Between Estimated Glucose Disposal Rate and Stroke in Middle-Aged and Older Chinese Adults: A Nationwide Prospective Cohort Study. J Am Heart Assoc 2025; 14:e039152. [PMID: 40281653 DOI: 10.1161/jaha.124.039152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Accepted: 03/25/2025] [Indexed: 04/29/2025]
Abstract
BACKGROUND The estimated glucose disposal rate (eGDR) is recognized as a reliable marker of insulin resistance. However, the association between eGDR and the risk of stroke remains unclear. METHODS AND RESULTS A total of 13 706 middle-aged and older participants were enrolled from CHARLS (China Health and Retirement Longitudinal Study). The primary end point was the occurrence of stroke events. The Kaplan-Meier curves, Cox proportional hazard models, and restricted cubic spline analysis were applied to explore the association between eGDR and the risk of stroke according to sex, age, and glycemic status. A total of 1101 stroke events were recorded. Our findings revealed a significant nonlinear relationship between eGDR and the occurrence of stroke. The association was similar between men (hazard ratio [HR], 0.83 [95% CI, 0.80-0.87]) and women (HR, 0.86 [95% CI, 0.80-0.87]), as well as among participants with normal glucose tolerance (HR, 0.83 [95% CI, 0.79-0.87]), prediabetes (HR, 0.85 [95% CI, 0.82-0.89]), and diabetes (HR, 0.87 [95% CI, 0.82-0.92]). However, the association was stronger in middle-aged participants (HR, 0.82 [95% CI, 0.78-0.86]) compared with older individuals (HR, 0.87 [95% CI, 0.83-0.90]; P for interaction=0.019). CONCLUSIONS This study demonstrates that lower eGDR levels are significantly linked to increased stroke risk. The relationship between eGDR and stroke risk was similar across different sexes and glycemic statuses and was stronger in middle-aged participants compared with older participants.
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Affiliation(s)
- Guijun Huo
- The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal Hospital Suzhou Jiangsu China
| | - Zhichao Yao
- The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal Hospital Suzhou Jiangsu China
| | - Xiaoqin Yang
- School of Biology and Basic Medical Sciences Suzhou Medical College of Soochow University Suzhou Jiangsu China
| | - Guanhui Wu
- The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal Hospital Suzhou Jiangsu China
| | - Lei Chen
- The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal Hospital Suzhou Jiangsu China
| | - Dayong Zhou
- The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal Hospital Suzhou Jiangsu China
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Yang Y, Shen H, Guan H, Wang B, Qing M, Liu J, Liu A. Effect of Statin on Clinical Outcomes in Critically Ill Patients with Non-traumatic Subarachnoid Hemorrhage: A Retrospective Analysis Based on MIMIC Database. World Neurosurg 2025; 197:123855. [PMID: 40054847 DOI: 10.1016/j.wneu.2025.123855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Accepted: 02/25/2025] [Indexed: 03/29/2025]
Abstract
BACKGROUND Nontraumatic subarachnoid hemorrhage (NSAH) is a type of hemorrhagic stroke with high mortality and low recovery rates. Although statins are commonly used in cardiovascular diseases, their impact on subarachnoid hemorrhage prognosis remains unclear. This study aimed to explore the relationship between statin use and short-term and long-term all-cause mortality in critically ill patients with NSAH. METHODS Data from the Medical Information Mart for Intensive Care IV database were used to categorize critically ill patients with NSAH into statin and nonstatin groups. A Cox proportional hazards model assessed the association between statin use and all-cause mortality. Subgroup analyses were conducted to examine the consistency of statin effects on mortality. RESULTS The study included 750 patients, with 43% male. One-month mortality was 21%, and intensive care unit mortality was 17%. Cox regression analysis showed that statin use was independently associated with reduced intensive care unit mortality (hazard ratio [HR = 0.52; P = 0.010), 1-month mortality (HR = 0.49; P < 0.001), 3-month mortality (HR = 0.62; P = 0.012), and 1-year mortality (HR = 0.70; P = 0.040). Subgroup analyses showed no significant interactions. Simvastatin and atorvastatin both significantly reduced 1-month mortality. CONCLUSIONS Statin use may improve mortality outcomes in critically ill patients with NSAH, suggesting their potential benefit in this population.
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Affiliation(s)
- Yibo Yang
- People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China; The Second Affiliated Hospital, Department of Neurosurgery, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Hui Shen
- Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Cerebrovascular Disease Department, Neurological Disease Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Hao Guan
- People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China
| | - Bing Wang
- The Second Affiliated Hospital, Department of Neurosurgery, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Mei Qing
- Department of Neurology, Beijing Pinggu Hospital, Beijing, China
| | - Jiachun Liu
- Cerebrovascular Disease Department, Neurological Disease Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China; Department of Neurosurgery, Beijing Hospital, Beijing, China
| | - Aihua Liu
- People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China; The Second Affiliated Hospital, Department of Neurosurgery, Hengyang Medical School, University of South China, Hengyang, Hunan, China; Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
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Vasudevan SS, Ericksen E, Albornoz V, Bryan E, Olinde L, Nathan CAO. Global Incidence, Mortality, and Risk Factors of Stroke in Multi-Modality Head and Neck Cancer Treatment-A Systematic Review and Meta-Analysis. Head Neck 2025; 47:1520-1540. [PMID: 39943713 DOI: 10.1002/hed.28109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 02/02/2025] [Accepted: 02/04/2025] [Indexed: 04/30/2025] Open
Abstract
BACKGROUND Head and neck cancer (HNC) due to its nature and proximity to essential vasculature, along with different treatments, can lead to stroke, significantly contributing to morbidity and mortality. Our aim is to systematically evaluate the association of stroke incidence, mortality, and predictors with HNC treatment. METHODS Pubmed, Web of Science, Embase, and ScienceDirect were searched from inception to July 2024 for articles reporting stroke incidences, mortality, or associated risk factors following treatment in HNC patients. A random-effects meta-analysis assessed cumulative incidence and mortality rates with proportional analysis and risk factors using hazard ratios (HRs) associated with HNC treatment. Subgroup analyses of incidence and mortality were conducted for pre- and post-2010 periods, reflecting changes in stroke protocols. RESULTS Out of 1561 studies, 69 studies with 258 850 HNC patients were included. The global cumulative incidence of stroke in HNC was 4.1% (95% CI: 3.3%-5.0%), with similar rates before and after 2010 (4.4% vs. 4.0%). In patients undergoing chemoradiotherapy (CRT), stroke incidence was 4.9% (95% CI: 3.5%-6.7%) with a median time to first stroke of 45 months (range: 14-51.7 months). Following radiation therapy (RT), stroke incidence was 3.8% (95% CI: 2.7%-5.3%) with a median time to stroke of 36 months (range: 6.8-130 months). The incidence rates of stroke in HNC patients were higher compared to the general population (HR: 1.69, 95% CI: 1.24-2.31, p = 0.001). Stroke mortality decreased from 28.5% (95% CI: 11.6%-54.9%) pre-2010 to 14.5% (95% CI: 11.6%-17.9%) 2010-2024. Stroke mortality was 39.3% (95% CI: 17.8%-66.0%) post-CRT and 21% (95% CI: 7.2%-47.7%) post-RT. Hypertension (HR = 1.75), diabetes (HR = 1.71), and age > 65 (HR = 2.17) increased stroke risk (p < 0.0001 for all). Geographically, South Korea (6.6%) had the highest incidence of stroke. CONCLUSION This is the first systematic review to analyze the association between stroke and HNC treatment. Stroke mortality decreased from 28.5% to 14.5% (pre-2010 vs. 2010-2024), with the highest mortality in the CRT group (39.3%). Given that stroke occurs 36-45 months after CRT, a screening protocol within 3-4 years is crucial.
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Affiliation(s)
- Srivatsa Surya Vasudevan
- Department of Otolaryngology-Head and Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA
| | - Elise Ericksen
- Louisiana State University Health Sciences Center School of Medicine, Shreveport, Louisiana, USA
| | - Victor Albornoz
- Department of Otolaryngology-Head and Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA
| | - Elizabeth Bryan
- Louisiana State University Health Sciences Center School of Medicine, Shreveport, Louisiana, USA
| | - Lindsay Olinde
- Department of Otolaryngology-Head and Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA
| | - Cherie-Ann O Nathan
- Department of Otolaryngology-Head and Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA
- Department of Surgery, Overton Brooks Veterans Administration Medical Center, Shreveport, Louisiana, USA
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18
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Bergmann F, Prager M, Pracher L, Sawodny R, Steiner‐Gager GM, Richter B, Jilma B, Zeitlinger M, Gelbenegger G, Jorda A. Systolic blood pressure targets below 120 mm Hg are associated with reduced mortality: A meta-analysis. J Intern Med 2025; 297:479-491. [PMID: 40041991 PMCID: PMC12032999 DOI: 10.1111/joim.20078] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/27/2025]
Abstract
BACKGROUND The optimal systolic blood pressure (SBP) target in patients with increased cardiovascular risk remains uncertain. This study evaluated the efficacy and safety of intensive SBP control (<120 mm Hg) compared to standard SBP control (<140 mm Hg) in patients with increased cardiovascular risk. METHODS We conducted a systematic search of PubMed, Embase, Web of Science, and Cochrane Library for RCTs published from database inception through November 2024 that compared intensive SBP control (<120 mm Hg) with standard SBP control (<140 mm Hg) in adults with high cardiovascular risk. Efficacy outcomes included all-cause mortality, major adverse cardiovascular events (MACE), cardiovascular death, stroke, myocardial infarction (MI), and heart failure. Safety outcomes included hypotension, syncope, arrhythmia, acute kidney injury, and electrolyte abnormalities. RESULTS Five RCTs comprising 39,434 patients were included. The all-cause mortality was significantly lower in the intensive SBP control group (672 of 19,712 [3.4%]) compared to the standard SBP control group (778 of 19,722 [3.9%]) (risk ratio 0.87 [95% confidence interval, 0.76-0.99, p = 0.03]). The incidence of MACE, cardiovascular death, MI, stroke, and heart failure was significantly lower in the intensive SBP control group as compared to standard SBP control group. The treatment effect (MACE) was consistent across all subgroups. Conversely, intensive SBP control was associated with an increased risk of hypotension, syncope, arrhythmia, acute kidney injury, and electrolyte abnormalities. CONCLUSIONS Targeting intensive SBP control to less than 120 mm Hg was associated with a lower incidence of all-cause mortality and MACE but a higher incidence of adverse events.
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Affiliation(s)
- Felix Bergmann
- Department of Clinical PharmacologyMedical University of ViennaViennaAustria
| | - Marlene Prager
- Department of Clinical PharmacologyMedical University of ViennaViennaAustria
| | - Lena Pracher
- Department of Clinical PharmacologyMedical University of ViennaViennaAustria
| | - Rebecca Sawodny
- Department of PathologyMedical University of ViennaViennaAustria
| | | | - Bernhard Richter
- Department of Medicine IIDivision of CardiologyMedical University of ViennaViennaAustria
| | - Bernd Jilma
- Department of Clinical PharmacologyMedical University of ViennaViennaAustria
| | - Markus Zeitlinger
- Department of Clinical PharmacologyMedical University of ViennaViennaAustria
| | - Georg Gelbenegger
- Department of Clinical PharmacologyMedical University of ViennaViennaAustria
| | - Anselm Jorda
- Department of Clinical PharmacologyMedical University of ViennaViennaAustria
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Pourahmad R, Saleki K, Zoghi S, Hajibeygi R, Ghorani H, Javanbakht A, Goodarzi S, Alijanizadeh P, Trinh K, Shastri R, Ghasemi-Rad M. Percutaneous transluminal angioplasty and stenting (PTAS) in patients with symptomatic intracranial vertebrobasilar artery stenosis (IVBS). Stroke Vasc Neurol 2025; 10:e003224. [PMID: 39168503 DOI: 10.1136/svn-2024-003224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 07/16/2024] [Indexed: 08/23/2024] Open
Abstract
BACKGROUND Approximately 20% of all transient ischaemic attacks (TIAs) and ischaemic strokes occur within the posterior circulation, with vertebrobasilar stenosis identified as the cause in roughly 25% of the cases. Studies have shown that about a quarter of these patients have atherosclerotic stenosis of at least 50% of the vertebrobasilar artery. Stenosis has been shown to be associated with an increased risk of 90-day recurrent vertebrobasilar stroke, particularly in the first few weeks, which is significantly higher when compared with patients with stenosis of the anterior circulation. Therefore, aggressive treatment is important for the patient's prognosis. Stenting is emerging as a promising therapeutic strategy for persistent ischaemia events that do not respond to the best medical treatment, but it is not without complications. We systematically reviewed the literature on percutaneous transluminal angioplasty and stenting (PTAS) for intracranial vertebrobasilar artery stenosis (IVBS). METHODS PubMed, Web-of-Science and Scopus were searched upon the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to include prospective/retrospective cohort, randomised/non-randomised clinical trials and case series studies describing PTAS for IVBS. Pooled rates of intervention-related complications and outcomes were analysed with random-effect model meta-analysis using StataMP V.18.0 software. RESULTS 31 studies were found eligible which included 1928 cases. 1103 basilar artery stenosis cases were reported in 27 studies 0.65 (95% CI 0.53, 0.76), I2: 99.72%. 648 vertebral cases were reported in 18 studies 0.60 (95% CI 0.49, 0.70), I2: 97.49%. In four studies, the rate of vertebrobasilar stenosis cases calculated as a proportion of the total sample size was 0.10 (95% CI 0.05, 0. 15). Mean stenosis in 21 included studies was found to be 0.83 (95% CI 0.79, 0.88), I2: 0.00%, which shows variation of baseline stenosis between studies was minimal. 51 deaths were recorded in 24 studies. Meta-analysis of mortality showed the overall rate of mortality was 0.03 (95% CI 0.02, 0.05), I2: 44.90%. In 14 studies, symptomatic intracranial haemorrhage events were recorded at an overall rate of 0.01 (95% CI 0.00, 0.02), I2: 0.00%. Generally, a follow-up period of at least 3 months was reported in the included studies. Furthermore, procedural stroke/TIA was evaluated in seven studies, four of which reported no events (0.03 (95% CI 0.00, 0.08), I2: 20.38%). Mean time from initial symptoms to recanalisation was 23.98 (95% CI 18.56, 29.40), I2=98.8%, p=0.00 days. CONCLUSION In certain individuals with medically unresolved, severe, symptomatic and non-acute IVBS, elective vertebrobasilar PTAS appears to be both safe and effective. Various stent designs and angioplasty-assisted techniques should be taken into consideration based on the specific clinical and radiological traits of the lesions. Future randomised controlled trials are required to verify these results.
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Affiliation(s)
- Ramtin Pourahmad
- Tehran University of Medical Sciences, Tehran, Iran (the Islamic Republic of)
| | - Kiarash Saleki
- Student Research Committee, Babol University of Medical Science, Babol, Iran (the Islamic Republic of)
- USERN Office, Babol University of Medical Sciences, Babol, Iran
| | - Sina Zoghi
- Shiraz Medical School, Shiraz, Iran (the Islamic Republic of)
| | - Ramtin Hajibeygi
- Tehran University of Medical Sciences, Tehran, Iran (the Islamic Republic of)
| | - Hamed Ghorani
- Tehran University of Medical Sciences, Tehran, Iran (the Islamic Republic of)
- Advanced Diagnostic and Interventional Radiology Research Center(ADIR), Tehran University of Medical Science, Tehran, Iran
| | - Amin Javanbakht
- Abadan University of Medical Sciences, Abadan, Iran (the Islamic Republic of)
| | - Sina Goodarzi
- Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran (the Islamic Republic of)
| | - Parsa Alijanizadeh
- Student Research Committee, Babol University of Medical Science, Babol, Iran (the Islamic Republic of)
- USERN Office, Babol University of Medical Sciences, Babol, Iran
| | - Kelly Trinh
- Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Ravi Shastri
- Department of radiology, Section of Vascular Interventional Radiology, Baylor College of Medicine, Houston, Texas, USA
| | - Mohammad Ghasemi-Rad
- Department of radiology, Section of Vascular Interventional Radiology, Baylor College of Medicine, Houston, Texas, USA
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Jiang B. Current Snapshots on Stroke Prevention and Control and More Proactive National Strategies Against It in China. J Cent Nerv Syst Dis 2025; 17:11795735251337605. [PMID: 40303445 PMCID: PMC12038203 DOI: 10.1177/11795735251337605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 04/09/2025] [Indexed: 05/02/2025] Open
Abstract
Background and Purpose Stroke has become a major public health problem. This paper aims to briefly review the current epidemiological characteristics, preliminary achievements, and national action strategies related to stroke prevention and control in China. Methods English and Chinese literature were searched on stroke epidemiological characteristics and more proactive strategies for its prevention and control in China. Potential papers related to this topic were identified from PubMed, Medline, Embase, Cochrane Library, Wanfang Database, SINOMED, and China National Knowledge Infrastructure databases, as well as the annual reports and websites of the People's Daily, the State Council, and the National Health Commission of the People's Republic of China. Results Stroke has been ranked among the top three causes of death in China, and has become a public health problem endangering people's health. High rates of incidence, mortality, and disability bring a heavy burden to stroke patients, families, and society. With China's economic development, urbanization, and population aging, the prevalence and incidence of stroke are still rising. Although some progress has been made in specialized stroke prevention and treatment in China, there is still much room for improvement. Curbing increasing stroke due to increased prevalence and suboptimal control of risk factors and unhealthy lifestyles is no longer just the efforts of medical service institutions. It still requires a more proactive national strategy and general mobilization of the whole people. Increased prevalence of stroke, survivors' unfavorable outcomes, and suboptimal rehabilitation also need specialized stroke care and the perfect Hierarchical Medical System within the regional medical consortium in China. Conclusions The current situation of stroke prevention and treatment is still very serious in China. In the future, the stroke prevention and treatment model will change from passive stroke treatment and risk factor control to a more proactive prevention model of health factor management.
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Affiliation(s)
- Bin Jiang
- Department of Neuroepidemiology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
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Liu J, Jiang S, Cui X, Bai X, Wen H, Zhao H, Wang H. Relationship between cardio-ankle vascular index value and stroke in hypertension patients cardio-ankle vascular index ≧9. PLoS One 2025; 20:e0321298. [PMID: 40273214 PMCID: PMC12021232 DOI: 10.1371/journal.pone.0321298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Accepted: 03/04/2025] [Indexed: 04/26/2025] Open
Abstract
BACKGROUNDS The cardio-ankle vascular index (CAVI) is a new index of arteriosclerosis. The present study investigated the relationship between CAVI value and stroke in hypertension patients, especially the prevalence of stroke in patients with CAVI ≧9. METHODS 735 patients (M/F 293/442) with or without hypertension from Department of Vascular Medicine from 01/01/2012-31/21/2014 were divided into four groups: group 1: non-hypertension patients with CAVI<9, group 2: non-hypertension patients with CAVI ≧9, group 3: hypertension patients with CAVI<9, group 4: hypertension patients with CAVI ≧9. CAVI was measured by VS-1000 apparatus. RESULTS Prevalence of stroke and coronary artery disease were significantly higher in group 2 than in group 1. And the prevalence of stroke and coronary artery disease were also significantly higher in group 4 than in group 3. In addition, the level of right intima-media thickness (RIMT) was significantly higher in group 4 than in group 3 (0.102±0.025 vs 0.094±0.023, p<0.05). Multiple linear regressions showed that CAVI and age were independent associating factors of stroke in all patients (β=0.268, p=0.040; β=0.135, p<0.001; respectively). CAVI was an independent associating factors of stroke in hypertension patients (β=0.398, p<0.001). CONCLUSION The prevalence of stroke was higher in hypertension patients with CAVI ≧9 than in hypertension patients with CAVI<9, with higher level of right intima-media thickness. CAVI was an independent associating factors of stroke in hypertension patients.
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Affiliation(s)
- Jinbo Liu
- Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, China
| | - Shantong Jiang
- Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, China
| | - Xuechen Cui
- Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, China
| | - Xiu Bai
- Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, China
| | - Huan Wen
- Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, China
| | - Hongwei Zhao
- Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, China
| | - Hongyu Wang
- Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, China
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Wang Z, Cao B, Yang M, Han J. A comment on "The impact of metabolic heterogeneity of obesity and transitions on cardiovascular disease incidence in Chinese middle-aged and elderly population: a nationwide prospective cohort study". J Transl Med 2025; 23:428. [PMID: 40217306 PMCID: PMC11987401 DOI: 10.1186/s12967-024-05969-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Accepted: 12/12/2024] [Indexed: 04/15/2025] Open
Affiliation(s)
- Zhiying Wang
- Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
- NHC Key Laboratory of Biotechnology Drugs, Shandong Academy of Medical Sciences, Jinan, China
| | - Baorui Cao
- Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
- NHC Key Laboratory of Biotechnology Drugs, Shandong Academy of Medical Sciences, Jinan, China
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Meina Yang
- Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
- NHC Key Laboratory of Biotechnology Drugs, Shandong Academy of Medical Sciences, Jinan, China.
| | - Jinxiang Han
- Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
- NHC Key Laboratory of Biotechnology Drugs, Shandong Academy of Medical Sciences, Jinan, China
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23
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An Y, Huang L, Li J, Chen Z, Cai J, Wang B, Zhou Q. LncRNA-mRNA co-expression network in the mechanism of butylphthalide treatment for ischemic stroke. BMC Neurol 2025; 25:155. [PMID: 40211238 PMCID: PMC11984060 DOI: 10.1186/s12883-025-04032-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 01/10/2025] [Indexed: 04/12/2025] Open
Abstract
BACKGROUND Butylphthalide has shown significant potential in the treatment of ischemic stroke, but its precise mechanisms of action remain unclear. Long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) play crucial roles in the pathogenesis of ischemic stroke and may serve as potential therapeutic targets. This study investigated the effects of butylphthalide treatment on the lncRNA-mRNA co-expression network in ischemic stroke patients. METHODS Peripheral blood samples were collected from ischemic stroke patients treated with butylphthalide and from control subjects. mRNA and lncRNA expression profiles were obtained using microarray scanning, and differentially expressed lncRNAs (DElncRNAs) were validated by qRT-PCR. Target genes interacting with DElncRNAs were predicted using the miRTargetLink database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on both DElncRNAs and differentially expressed mRNAs (DEmRNAs). A protein-protein interaction (PPI) network was constructed for proteins encoded by DEmRNAs. Co-expression analysis, based on Pearson correlation coefficients, identified the top five mRNAs and lncRNAs with high connectivity. Finally, molecular docking was performed to investigate the binding interaction between butylphthalide and key mRNAs. RESULTS A total of 86 differentially expressed mRNAs (69 upregulated, 17 downregulated) and 35 DElncRNAs (all upregulated) were identified. DEmRNAs were primarily associated with pathways related to cell receptors, signal transduction, cell proliferation, migration, and glucose metabolism, while DElncRNAs were involved in processes such as embryonic development, neuronal connectivity, and energy metabolism. Co-expression analysis identified key mRNA nodes (SETD9, ZNF718, AOC2, MPND, ODF1) and lncRNA nodes (IDH2-DT, CLEC12A-AS1, CARD8-AS1, LINC01275, ZNF436-AS1). Molecular docking analysis suggested that MT-CO1, SETD9, and ZNF718 could be potential targets of butylphthalide. CONCLUSION Butylphthalide may exert its therapeutic effects by regulating the LncRNA-mRNA co-expression network, influencing energy metabolism and neuronal development. This provides new insights into its mechanism of action and potential therapeutic targets.
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Affiliation(s)
- Yangfang An
- Department of Neurology, Yiyang Central Hospital, Yiyang, Hunan, 413000, China
| | - Lingyun Huang
- Department of Neurology, Yiyang Central Hospital, Yiyang, Hunan, 413000, China
| | - Jun Li
- Department of Neurology, Yiyang Central Hospital, Yiyang, Hunan, 413000, China
| | - Zhuo Chen
- Department of Neurology, Yiyang Central Hospital, Yiyang, Hunan, 413000, China
| | - Jizhang Cai
- Department of Neurology, Yiyang Central Hospital, Yiyang, Hunan, 413000, China
| | - Biao Wang
- Department of Neurology, Yiyang Central Hospital, Yiyang, Hunan, 413000, China
| | - Qiong Zhou
- Department of Neurology, Yiyang Central Hospital, Yiyang, Hunan, 413000, China.
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Alhawiti NM, Elsokkary EM, Aldali JA, Alotaibi BA. Investigating the impact of glycated hemoglobin levels on stroke severity in patients with acute ischemic stroke. Sci Rep 2025; 15:12114. [PMID: 40204797 PMCID: PMC11982240 DOI: 10.1038/s41598-025-95305-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Accepted: 03/20/2025] [Indexed: 04/11/2025] Open
Abstract
Stroke is a sudden neurological decline caused by cerebrovascular diseases or impaired blood circulation. Research investigating the connection between glycated hemoglobin A1c (HbA1c) levels and stroke severity is limited. This study examined the connection between HbA1c levels and stroke severity in patients with acute ischemic stroke. A retrospective cross-sectional analysis of the medical records of 1103 patients with acute ischemic stroke from January 2020 to January 2024 was conducted. Patients were divided into seven groups on the basis of their HbA1c levels. Stroke severity within these groups was assessed via the National Institutes of Health Stroke Scale (NIHSS), with the aim of identifying correlations between stroke severity and glycemic status. This study examined the impact of various HbA1c levels on a range of demographic and clinical characteristics in stroke patients. The patients were grouped into seven categories on the basis of their HbA1c levels, and characteristics such as age; body mass index (BMI); LDL, HDL, and creatinine levels; and NIHSS scores at hospital admission were compared across these groups. Significant differences were observed in age, LDL levels (F = 3.999, P < 0.001), and creatinine levels (F = 1.303, P = 0.253) among the HbA1c categories. However, there were no significant differences in BMI, HDL levels, or length of hospital stay. A positive correlation was found between HbA1c levels and NIHSS scores, indicating that higher HbA1c levels are associated with greater stroke severity. This study revealed that the risk of severe stroke increases significantly when HbA1c levels exceed 6.5%. In contrast, maintaining HbA1c levels below 6.5% is linked to a reduced risk of severe stroke and lower mortality. Additionally, older adults are at greater risk and tend to experience more severe strokes.
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Affiliation(s)
- Naif M Alhawiti
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
| | - Emadeldin M Elsokkary
- Department of Psychology, College of Social Sciences, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 13317, Saudi Arabia
| | - Jehad A Aldali
- Department of Pathology, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 13317, Saudi Arabia
| | - Badi A Alotaibi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
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25
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Sun Z, Zheng Y. Metabolic diseases in the East Asian populations. Nat Rev Gastroenterol Hepatol 2025:10.1038/s41575-025-01058-8. [PMID: 40200111 DOI: 10.1038/s41575-025-01058-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/05/2025] [Indexed: 04/10/2025]
Abstract
East Asian populations, which account for approximately 20% of the global population, have become central to the worldwide rise of metabolic diseases over the past few decades. The prevalence of metabolic disorders, including type 2 diabetes mellitus, hypertension and metabolic dysfunction-associated steatotic liver disease, has escalated sharply, contributing to a substantial burden of complications such as cardiovascular disease, chronic kidney disease, cancer and increased mortality. This concerning trend is primarily driven by a combination of genetic predisposition, unique fat distribution patterns and rapidly changing lifestyle factors, including urbanization and the adoption of Westernized dietary habits. Current advances in genomics, proteomics, metabolomics and microbiome research have provided new insights into the biological mechanisms that might contribute to the heightened susceptibility of East Asian populations to metabolic diseases. This Review synthesizes epidemiological data, risk factors and biomarkers to provide an overview of how metabolic diseases are reshaping public health in East Asia and offers insights into biological and societal drivers to guide effective, region-specific strategies.
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Affiliation(s)
- Zhonghan Sun
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yan Zheng
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
- Department of Nutrition and Food Hygiene, School of Public Health, Institute of Nutrition, Fudan University, Shanghai, China.
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Sun Y, Zhong Q, Hou Y, Liu X, Yan M, Zhou L, Liu S, Hong S, He J. Effect of DU meridian acupuncture and temporal three-needle on vascular protection mechanisms in patients with acute cerebral infarction: a randomized controlled evaluator-blinded clinical trial. Front Neurol 2025; 16:1528340. [PMID: 40260140 PMCID: PMC12009876 DOI: 10.3389/fneur.2025.1528340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Accepted: 03/26/2025] [Indexed: 04/23/2025] Open
Abstract
Background The incidence of acute ischemic stroke has been rising steadily in China and globally, with its high mortality and disability rates significantly affecting quality of life. As an important adjunct therapy, acupuncture has been widely implemented in stroke management. Emerging studies have investigated the effects of DU meridian and Chong Mai acupuncture on ischemic hemiparesis; however, the vascular protective mechanisms of electroacupuncture therapy targeting these meridians require further elucidation in stroke rehabilitation research. Objective This prospective cohort study aims to investigate the clinical efficacy and limitations of DU meridian acupuncture combined with Temporal Triple Needling (Sanjian) therapy in stroke rehabilitation. The intervention's therapeutic potential is evaluated through its modulatory effects on CD14+/CD14- monocyte subpopulations within peripheral blood mononuclear cells (PBMCs), with particular focus on angiogenesis-mediated vascular protection mechanisms. Methods Sixty-six patients with acute ischemic stroke will be randomly assigned 1:1 to control (conventional basal therapy, n = 33) and acupuncture (conventional standard stroke care + acupuncture, n = 33) groups for 10 days of intervention. The primary outcome is NIHSS score. The secondary outcomes: BMI and mRS scores, the level of TNF-A and IL-1B in serum, vascular endothelial growth factor (VEGF), Endocan ES, CD14+ and CD14- levels of peripheral blood mononuclear cells. Discussion The aim of this study is to investigate whether electroacupuncture targeting the DU meridian combined with Temporal Triple Needling (Sanjian) improves cerebrovascular endothelial function in acute ischemic stroke patients, thereby reducing the NIHSS score and preventing further disease progression. This study also aims to contribute positively to the development of relevant clinical treatment protocols and to facilitate further research into the underlying mechanisms of these effects. Clinical trial registration International Traditional Medicine Clinical Trial Registry ITMCTR2024000508.
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Affiliation(s)
- Yawen Sun
- First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qiqi Zhong
- First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yingci Hou
- First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xin Liu
- First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Mingyue Yan
- First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Luolin Zhou
- First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Shiyi Liu
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Senkai Hong
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jun He
- First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
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27
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Jiang M, Sun L, Jia Y, Ren X, Han L, Zhu Z, Zheng X. Causal effects of Annexin A1 and Annexin A2 on ischemic stroke and its subtypes: A two-sample Mendelian randomization study. J Cardiol 2025:S0914-5087(25)00099-1. [PMID: 40187529 DOI: 10.1016/j.jjcc.2025.03.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 03/26/2025] [Accepted: 03/27/2025] [Indexed: 04/07/2025]
Abstract
BACKGROUND Preclinical studies have suggested that Annexin A1 and Annexin A2 act as anti-inflammatory agents, slowing the progression of atherosclerosis and further potentially reducing the risk of ischemic stroke. Since the causality of Annexins and ischemic stroke remains uncertain, this study aimed to investigate the causal effects of both using a two-sample Mendelian randomization (MR) method. METHODS The genetic instruments associated with Annexin A1 and Annexin A2 originated from a European-descent genome-wide association study (GWAS) of 50,000 participants from the INTERVAL study. Summary statistics for ischemic stroke and ischemic stroke subtypes were derived from the MEGASTROKE consortium's GWAS dataset, involving 40,585 cases and 406,111 controls of European ancestry. The inverse-variance weighted method was utilized in the main analysis, followed by a series of sensitivity analyses for robustness validation. RESULTS In the primary analysis, genetically predicted high Annexin A1 levels were associated with decreased risks of ischemic stroke (OR = 0.96; 95 % CI = 0.93-0.99; p = 0.023) and large artery stroke (OR = 0.88; 95 % CI = 0.81-0.96; p = 0.004). Similarly, genetically predicted high Annexin A2 levels also had significant associations with decreased risks of ischemic stroke (OR = 0.97; 95 % CI = 0.95-1.00; p = 0.019) and large artery stroke (OR = 0.90; 95 % CI = 0.85-0.96; p = 0.001). CONCLUSION In this two-sample MR study, we found that Annexins had causal protective effects against ischemic stroke, especially large artery stroke. Further basic mechanistic studies should be conducted to investigate the biological roles of these genes.
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Affiliation(s)
- Minglan Jiang
- Public Health Research Center and Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China
| | - Lulu Sun
- Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China
| | - Yiming Jia
- Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China
| | - Xiao Ren
- Public Health Research Center and Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China
| | - Longyang Han
- Public Health Research Center and Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China
| | - Zhengbao Zhu
- Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China.
| | - Xiaowei Zheng
- Public Health Research Center and Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China; Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China.
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28
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Luo L, Hu Q, Yan R, Gao X, Zhang D, Yan Y, Liu Q, Mao S. Alpha‑Asarone Ameliorates Neuronal Injury After Ischemic Stroke and Hemorrhagic Transformation by Attenuating Blood-Brain Barrier Destruction, Promoting Neurogenesis, and Inhibiting Neuroinflammation. Mol Neurobiol 2025; 62:5252-5272. [PMID: 39531192 DOI: 10.1007/s12035-024-04596-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 10/25/2024] [Indexed: 11/16/2024]
Abstract
Recombinant tissue-type plasminogen activator (rt-PA), the primary drug for acute ischemic stroke (IS), has a narrow therapeutic window and carries a potential risk of hemorrhagic transformation (HT). Without rt-PA administration, patients may suffer permanent cerebral ischemia. Alpha-asarone (ASA), a natural compound derived from Acorus tatarinowii Schott, exhibits diverse neuropharmacological effects. This study aims to investigate whether ASA could improve outcomes in IS and be used to mitigate HT induced by rt-PA. We employed models of permanent middle cerebral artery occlusion (pMCAO) and photothrombotic cortical injury (PCI) to investigate both the therapeutic efficacy and underlying mechanisms of ASA during the acute and recovery periods following IS, respectively. Additionally, Sprague-Dawley rats were subjected to rt-PA treatment at 6-h post-PCI to mimic HT (rt-PA-HT). Our results revealed three key findings: (1) ASA demonstrated therapeutic effects in the acute phase of pMCAO rats by alleviating blood-brain barrier damage through inhibition of glial cell-mediated neuroinflammation; (2) administration of ASA 24 h after stroke ameliorated the neurological damage during the recovery phase in PCI mice by promoting neurogenesis via activation of the BDNF/ERK/CREB signaling pathway; (3) ASA attenuated rt-PA-HT injury by modulating the NLRP3/Caspase1/IL-1β and IL-18 pathways. Overall, our findings suggest that ASA mitigates neuronal injury following IS and HT, positioning it as a promising candidate for treating these conditions.
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Affiliation(s)
- Lijun Luo
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Qinrui Hu
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Ruijie Yan
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Xiaofeng Gao
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Di Zhang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Yi Yan
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Qi Liu
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Shengjun Mao
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
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29
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Huang J, Bao C, Yang C, Qu Y. Dual-tDCS Ameliorates Cerebral Injury and Promotes Motor Function Recovery via cGAS-STING Signaling Pathway in a Rat Model of Ischemic Stroke. Mol Neurobiol 2025; 62:4484-4498. [PMID: 39455539 DOI: 10.1007/s12035-024-04574-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 10/21/2024] [Indexed: 10/28/2024]
Abstract
Ischemic stroke is one of the leading causes of death and disability. Dual transcranial direct current stimulation (dual-tDCS) is a promising intervention to treat ischemic stroke, but its efficacy and underlying mechanism remain to be verified. Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has recently emerged as a key mediator in cerebral injury. However, little is known about the effect of cGAS-STING on neuronal damage in ischemic stroke, and it remains to be studied whether the cGAS-STING pathway is involved in tDCS intervention for ischemic stroke. Therefore, we aimed to investigate whether dual-tDCS can alleviate ischemic brain injury in a rat model of ischemic stroke and if so, whether via cGAS-STING pathway. Middle cerebral artery occlusion (MCAO) was employed to induce a rat model of ischemic stroke. Male SD rats weighing 250-280 g were randomly assigned to the Sham, MCAO, Dual-tDCS, Dual-tDCS + RU.521, and Dual-tDCS + 2'3'-cGAMP groups, with 10 rats in each group completing the experiment. Behavioral, morphological, MRI, and molecular biological methods were performed. We found that the cGAS-STING pathway was activated and expressed in neurons after MCAO. Dual-tDCS improved motor function and infarct volume, inhibited neuronal apoptosis, promoted the expression of neurotrophins (BDNF and NGF), CD31, and VEGF, and suppressed inflammation reaction after MCAO via the cGAS-STING pathway. Taken together, dual-tDCS may improve MCAO-induced brain injury and promote the recovery of motor function, resulting from the inhibition of neuronal apoptosis and inflammation reaction, as well as promotion of the expression of nerve plasticity- and angiogenesis-related proteins, via cGAS-STING pathway.
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Affiliation(s)
- Jiapeng Huang
- Clinical Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China
- Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
- Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
- Research Laboratory of Neurorehabilitation, Research Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Chuncha Bao
- Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
- Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Chunlan Yang
- Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
- Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
- Research Laboratory of Neurorehabilitation, Research Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yun Qu
- Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
- Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
- Research Laboratory of Neurorehabilitation, Research Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
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30
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Wang J, Zeng G, Tang R, Luo H, Song Y, Zhou Y, Huang J, Zhu S, Zhang D, Liu D, Liu R, Huang S, Yuan C, Zhu J, Zhang X. Data-Driven Subtypes of Parkinson Disease Based on Dopamine Responsiveness. CNS Neurosci Ther 2025; 31:e70408. [PMID: 40272005 PMCID: PMC12019691 DOI: 10.1111/cns.70408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2025] [Revised: 03/27/2025] [Accepted: 04/13/2025] [Indexed: 04/25/2025] Open
Abstract
AIMS Parkinson disease (PD) is highly heterogeneous in response to antiparkinsonian drugs. We herein aimed to identify PD subtypes based on dopamine responsiveness in three key motor signs (resting tremor, rigidity, and bradykinesia). METHODS The acute levodopa challenge test was performed. Improvement rates in resting tremor, rigidity, and bradykinesia were calculated. A total of 228 PD patients were included for further analysis. Subtypes were determined by k-means clustering based on the improvement rates. RESULTS Four subtypes were identified: rt-r-b, moderate improvement in resting tremor, rigidity, and bradykinesia; RT-r-b, marked improvement in resting tremor but moderate improvement in rigidity and bradykinesia; RT-R-B, marked improvement in resting tremor, rigidity, and bradykinesia; rt-R-B, moderate improvement in resting tremor but marked improvement in rigidity and bradykinesia. These subtypes also differed in other motor and nonmotor symptoms. CONCLUSION Our study reveals four distinct subtypes in PD patients based on dopamine responsiveness. Our findings provide a novel insight into understanding PD heterogeneity and facilitate precision treatment.
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Affiliation(s)
- Jian‐Yong Wang
- Department of Neurology and Institute of Geriatric Neurology, The Second Affiliated Hospital and Yuying Children's HospitalWenzhou Medical UniversityWenzhouZhejiangChina
| | - Guo‐Ling Zeng
- Department of Neurology and Institute of Geriatric Neurology, The Second Affiliated Hospital and Yuying Children's HospitalWenzhou Medical UniversityWenzhouZhejiangChina
| | - Rong‐Ting Tang
- Institute of Nutrition and Diseases and Center for Research, School of Public HealthWenzhou Medical UniversityWenzhouZhejiangChina
| | - Hai‐Tao Luo
- Institute of Nutrition and Diseases and Center for Research, School of Public HealthWenzhou Medical UniversityWenzhouZhejiangChina
| | - Yu‐Lian Song
- Institute of Nutrition and Diseases and Center for Research, School of Public HealthWenzhou Medical UniversityWenzhouZhejiangChina
| | - Yang‐Yang Zhou
- Institute of Nutrition and Diseases and Center for Research, School of Public HealthWenzhou Medical UniversityWenzhouZhejiangChina
| | - Jie‐Fan Huang
- Department of Nuclear Medicine, The Second Affiliated Hospital and Yuying Children's HospitalWenzhou Medical UniversityWenzhouZhejiangChina
| | - Shi‐Guo Zhu
- Department of Neurology and Institute of Geriatric Neurology, The Second Affiliated Hospital and Yuying Children's HospitalWenzhou Medical UniversityWenzhouZhejiangChina
| | - Dao‐Lu Zhang
- Institute of Nutrition and Diseases and Center for Research, School of Public HealthWenzhou Medical UniversityWenzhouZhejiangChina
| | - Dan‐Ni Liu
- Department of Neurology and Institute of Geriatric Neurology, The Second Affiliated Hospital and Yuying Children's HospitalWenzhou Medical UniversityWenzhouZhejiangChina
| | - Rong‐Pei Liu
- Department of Neurology and Institute of Geriatric Neurology, The Second Affiliated Hospital and Yuying Children's HospitalWenzhou Medical UniversityWenzhouZhejiangChina
| | - Shi‐Shi Huang
- Department of Neurology and Institute of Geriatric Neurology, The Second Affiliated Hospital and Yuying Children's HospitalWenzhou Medical UniversityWenzhouZhejiangChina
| | - Cheng‐Xiang Yuan
- Department of Neurology and Institute of Geriatric Neurology, The Second Affiliated Hospital and Yuying Children's HospitalWenzhou Medical UniversityWenzhouZhejiangChina
| | - Jian‐Hong Zhu
- Institute of Nutrition and Diseases and Center for Research, School of Public HealthWenzhou Medical UniversityWenzhouZhejiangChina
| | - Xiong Zhang
- Department of Neurology and Institute of Geriatric Neurology, The Second Affiliated Hospital and Yuying Children's HospitalWenzhou Medical UniversityWenzhouZhejiangChina
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31
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M’barek L, Jin A, Pan Y, Lin J, Jiang Y, Meng X, Wang Y. Stroke Prognosis: The Impact of Combined Thrombotic, Lipid, and Inflammatory Markers. J Atheroscler Thromb 2025; 32:458-473. [PMID: 39462537 PMCID: PMC11973529 DOI: 10.5551/jat.64984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Accepted: 08/25/2024] [Indexed: 10/29/2024] Open
Abstract
AIM D-dimer, lipoprotein (a) (Lp(a)), and high-sensitivity C-reactive protein (hs-CRP) are known predictors of vascular events; however, their impact on the stroke prognosis is unclear. This study used data from the Third China National Stroke Registry (CNSR-III) to assess their combined effect on functional disability and mortality after acute ischemic stroke (AIS). METHODS In total, 9,450 adult patients with AIS were enrolled between August 2015 and March 2018. Patients were categorized based on a cutoff value for D-dimer, Lp(a), and hs-CRP in the plasma. Adverse outcomes included poor functional outcomes (modified Rankin Scale (mRS score ≥ 3)) and one- year all-cause mortality. Logistic and multivariate Cox regression analyses were performed to investigate the relationship between individual and combined biomarkers and adverse outcomes. RESULTS Patients with elevated levels of all three biomarkers had the highest odds of functional disability (OR adjusted: 2.01; 95% CI (1.47-2.74); P<0.001) and mortality (HR adjusted: 2.93; 95% CI (1.55-5.33); P<0.001). The combined biomarkers improved the predictive accuracy for disability (C-statistic 0.80 vs.0.79, P<0.001) and mortality (C-statistic 0.79 vs.0.78, P=0.01). CONCLUSION Elevated D-dimer, Lp(a), and hs-CRP levels together increase the risk of functional disability and mortality one-year post-AIS more than any single biomarker.
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Affiliation(s)
- Lamia M’barek
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Aoming Jin
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yuesong Pan
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Jinxi Lin
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yong Jiang
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Xia Meng
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yongjun Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
- Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, 2019RU018, Beijing, China
- Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
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Shi H, Su M, Shen P, Ma J, Zhou Q, Yang Z, Chai P, Sun S, Lin H, Shui L, Liang Z, Huang S, Zhang N, Wang J, Chen K, Zhang Z. Associations Between Metals and Nonmetals in Drinking Water, Cardiovascular Events, and Diet. JACC. ADVANCES 2025; 4:101669. [PMID: 40117693 PMCID: PMC11978338 DOI: 10.1016/j.jacadv.2025.101669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2024] [Revised: 01/16/2025] [Accepted: 01/19/2025] [Indexed: 03/23/2025]
Abstract
BACKGROUND Metals and nonmetals in drinking water could potentially influence cardiovascular health. The relationship between poor-quality drinking water, major adverse cardiovascular events (MACE), and diet is not well studied. OBJECTIVES The aim of this study was to determine whether long-term exposure to metals (copper, manganese, aluminum, zinc, and cadmium) and nonmetals (selenium, sulfate, and nitrate-nitrogen) in drinking water was associated with MACE outcomes, and whether the dietary patterns could modify the association between long-term exposure to low-quality drinking water and MACE. METHODS Data from a prospective population-based cohort from Yinzhou District, Ningbo (follow-up between 2016 and 2022) were linked to Yinzhou Health Information System. MACE endpoints included acute myocardial infarction (AMI), heart failure, stroke, angina, and cardiovascular death. Effect modification of the associations between exposure and MACE by dietary factors was determined. RESULTS In the final cohort of 24,212 participants, 57 had an AMI; 886 developed heart failure; 733 had a stroke; 23 had angina; and 134 had a cardiovascular death. An increased risk of: 1) AMI was seen with exposure to copper, aluminum, cadmium, and selenium; 2) stroke with exposure to zinc, copper, and selenium; 3) angina with exposure to zinc and copper; and 4) cardiovascular death with exposure to zinc and aluminum in drinking water. Consuming fish, white meat, and grain products attenuated MACE outcomes induced by metals and nonmetals in drinking water. CONCLUSIONS In this study, long-term exposure to higher metallic and nonmetallic elements in drinking water was associated with an increased risk of MACE. Specific dietary patterns modified the associations. Further studies are needed in this area.
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Affiliation(s)
- Hanxu Shi
- School of Public Health, Institute of Environmental Medicine, Peking University School of Public Health, Beijing, China
| | - Mintao Su
- School of Public Health, Institute of Environmental Medicine, Peking University School of Public Health, Beijing, China
| | - Peng Shen
- Yinzhou District Center for Disease Control and Prevention, Ningbo, China
| | - Junxiong Ma
- School of Public Health, Institute of Environmental Medicine, Peking University School of Public Health, Beijing, China
| | - Qinfeng Zhou
- School of Public Health, Institute of Environmental Medicine, Peking University School of Public Health, Beijing, China
| | - Zongming Yang
- Department of Public Health, and Department of National Clinical Research Center for Child Health, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Pengfei Chai
- Yinzhou District Center for Disease Control and Prevention, Ningbo, China
| | - Shengzhi Sun
- School of Public Health, Capital Medical University, Beijing, China
| | - Hongbo Lin
- Yinzhou District Center for Disease Control and Prevention, Ningbo, China
| | - Liming Shui
- Yinzhou District Health Bureau of Ningbo, Ningbo, China
| | - Zhisheng Liang
- School of Public Health, Institute of Environmental Medicine, Peking University School of Public Health, Beijing, China
| | - Shuyu Huang
- School of Public Health, Institute of Environmental Medicine, Peking University School of Public Health, Beijing, China
| | - Na Zhang
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, China
| | - Jianbing Wang
- Department of Public Health, and Department of Endocrinology of the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children's Health, Hangzhou, China.
| | - Kun Chen
- Department of Public Health, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
| | - Zhenyu Zhang
- School of Public Health, Institute of Environmental Medicine, Peking University School of Public Health, Beijing, China; Institute for Global Health and Development, Peking University, Beijing, China; Institute of Carbon Neutrality, Peking University, Beijing, China.
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Qin S, Gao S, Xu D, Zhang L, Luo Y, Guo S. Ticagrelor or dipyridamole plus aspirin may be a promising antiplatelet therapy in patients with minor stroke or transient ischemic attack: a bayesian network meta-analysis. Front Pharmacol 2025; 16:1561564. [PMID: 40206092 PMCID: PMC11978618 DOI: 10.3389/fphar.2025.1561564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Accepted: 03/17/2025] [Indexed: 04/11/2025] Open
Abstract
Background The efficacy and safety of different antiplatelet in minor strokes or transient ischemic attacks (TIAs) remains controversial. Methods We searched PubMed, Embase, Web of Science and the Cochrane Library to identify all eligible articles until 12 September 2024. Efficacy outcomes were all-cause mortality, excellent outcome, functional independence and recurrent stroke. Safety outcomes were any types of bleeding and intracerebral hemorrhage (ICH). The associations were calculated for the overall data by using the odds ratios (ORs). Results 12 high-quality studies with 10 RCTs and 2 Non-RCTs were included, involving 61,281 patients with minor strokes or TIAs. Ticagrelor + Aspirin was significantly more effective than Clopidogrel + Aspirin in preventing post-stroke neurological dysfunctions (mRS 0-1), recurrent stroke and major vascular events for up to 90 days. But Ticagrelor + Aspirin is associated with an increased risk of any bleeding and mild bleeding at 90 days, and there is no significant difference in other bleeding risks. The risk of any bleeding in Dipyridamole + Aspirin is not significantly different from that in Aspirin, and is even significantly lower than in Ticagrelor. Compared with other dual antiplatelet therapies (DAPTs), Dipyridamole + Aspirin had no significant difference in the risk of all-cause mortality and major vascular events during follow-up. Conclusion For minor strokes or TIAs with a low bleeding risk or CYP2C19 loss-of-function alleles, Ticagrelor + Aspirin may be a better choice than Clopidogrel + Aspirin. Due to limited studies, the superiority of Dipyridamole + Aspirin is still difficult to conclude, and further high-quality studies are needed to verify the benefits of Dipyridamole + Aspirin in minor stroke or TIAs. Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier CRD42024537462.
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Affiliation(s)
| | | | | | | | - Yanmei Luo
- Department of Pharmacy, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Sitong Guo
- Department of Pharmacy, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
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Fei S, Xu M, Liu Z, Xie H, Yu Y, Chu Y, Zhu L, Fang Z, Jin Y, Yao Y, Chen Y. Molecular epidemiological study of exosomes circZNF609, circPUM1, IGF2 with ischemic stroke. BMC Cardiovasc Disord 2025; 25:215. [PMID: 40133811 PMCID: PMC11934478 DOI: 10.1186/s12872-025-04663-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 03/13/2025] [Indexed: 03/27/2025] Open
Abstract
BACKGROUND Ischemic stroke (IS) is a common cardiovascular disease (CVD). Insulin-like growth factor 2 (IGF2), circZNF609, and circPUM1 are involved in metabolic regulation, vascular health, neuroprotection, and inflammation modulation and are relevant to IS mechanisms. This study investigated the effects of plasma exosomal expression of circZNF609, circPUM1, and IGF2 on IS. METHODS The expression of circZNF609, circPUM1, and IGF2 mRNA in exosomes was detected in 145 patients with IS and 290 controls using real-time qPCR in a cross-sectional study. Q1-Q4 represents the quartile groups based on the target gene expression levels. RESULTS There was no significant difference in the expression levels of circZNF609 and circPUM1 in the plasma exosomes between the IS and control groups (P > 0.05). However, a nonlinear relationship between the expression levels of circZNF609 in the IS group (P < 0.05). Exosomal IGF2 mRNA expression in the IS group was significantly lower than that in the control group (P = 0.043). The multifactorial adjusted results showed that in the case-control study of IS, circZNF609 in plasma exosomes was associated with a reduced risk of disease in group Q2 (adjusted OR: 0.565; P = 0.035) compared to that in group Q1, the low-expression group. In plasma exosomes, circZNF609 expression in group Q4 was associated with a reduced risk of disease in group Q1 (adjusted OR: 0.654; P = 0.004) compared to that in group Q1 (low expression). Plasma exosomes with IGF2 showed a reduced risk in the Q4 group with high IGF2 expression compared to that in the Q1 group with low IGF2 expression (adjusted OR: 0.543; P = 0.042). CONCLUSIONS This study suggests that the low expression of circZNF609, circPUM1, and IGF2 in peripheral blood plasma exosomes could pose a potential risk for IS and serve as biomarkers for clinical treatment.
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Affiliation(s)
- Suhai Fei
- School of Public Health, Wannan Medical College, Wuhu, China
- The Fourth People'S Hospital of Wuhu, Wuhu, China
| | - Miao Xu
- School of Public Health, Wannan Medical College, Wuhu, China
| | - ZhenFeng Liu
- School of Public Health, Wannan Medical College, Wuhu, China
| | - Haining Xie
- School of Public Health, Wannan Medical College, Wuhu, China
| | - Yue Yu
- School of Public Health, Wannan Medical College, Wuhu, China
| | - Yinghu Chu
- School of Public Health, Wannan Medical College, Wuhu, China
| | - Lijun Zhu
- School of Public Health, Wannan Medical College, Wuhu, China
| | - Zhengmei Fang
- School of Public Health, Wannan Medical College, Wuhu, China
| | - Yuelong Jin
- School of Public Health, Wannan Medical College, Wuhu, China
| | - Yingshui Yao
- School of Public Health, Wannan Medical College, Wuhu, China.
| | - Yan Chen
- School of Public Health, Wannan Medical College, Wuhu, China.
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Guo L, Cao X, Chang L, Liu H. Neutrophil-to-lymphocyte ratio as a predictor of prognosis in patients with spontaneous intracerebral hemorrhage: a systematic review and meta-analysis. Front Neurol 2025; 16:1553263. [PMID: 40191597 PMCID: PMC11968378 DOI: 10.3389/fneur.2025.1553263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Accepted: 03/05/2025] [Indexed: 04/09/2025] Open
Abstract
Objective To evaluate the predictive value of the neutrophil-to-lymphocyte ratio (NLR) for prognosis spontaneous intracerebral hemorrhage (ICH) patients. Methods PubMed, EMBASE, Cochrane Library, Web of Science were used for screening literature on NLR predicting ICH prognosis from database up to January 2024. Case-control or cohort studies that provided statistical analysis data on NLR predicting ICH prognosis were included. Data were combined using odds ratio (OR) and standard mean differences (SMD) for categorical variables and continuous variables, respectively. Meta-analysis, subgroup analyses, and sensitivity analyses were performed by Review Manager 5.4 and Stata 15.0. Results Meta-analysis of 21 studies with a total of 7,176 patients confirmed that NLR has a significant predictive value for mortality (SMD: 0.80, 95% CI: 0.58-1.02; OR: 1.10, 95% CI: 1.04-1.17) and neurological function outcomes (SMD: 0.66, 95% CI: 0.50-0.81; OR: 1.29, 95% CI: 1.17-1.41). NLR also significantly predicted the occurrence of stroke-associated pneumonia (SAP) (SMD: 0.54, 95% CI: 0.21-0.87). Subgroup analysis suggested that NLR had good predictive value for mortality in ICH patients aged ≥60 years, with hematoma volume > 15 mL, and NLR cut-off >7.5, and for neurological function in ICH patients, Asian patients, and those with NLR cut-off >7.5. The stability of the results was confirmed by sensitivity analysis. Conclusion NLR can significantly predict mortality, neurological function outcomes, and SAP occurrence in ICH patients. NLR cut-off >7.5 has good predictive value for both mortality and neurological function in ICH patients. Considering the limitations of this study, such as small sample size and potential heterogeneity, prospective studies with larger sample sizes are needed to confirm the findings of this article. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024544506.
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Affiliation(s)
- Lixia Guo
- Department of Medical College, Tibet University, Lhasa, China
| | - Xudong Cao
- Department of Neurosurgery, Tibet Autonomous Region People's Hospital, Lhasa, China
| | - Luyao Chang
- Department of Medical College, Tibet University, Lhasa, China
| | - Huandong Liu
- Department of Neurosurgery, Tibet Autonomous Region People's Hospital, Lhasa, China
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Sun M, Wang Y, Xu H, Shen Y, Liu B, Ma Y, Jiang C, Wang S, Li Q, Lu Y, Han F, Li T, Qin Y. Novel Hypochlorous Acid-Activated Near-Infrared Probe Monitors the Dynamic Changes of Myeloperoxidase Activity in Ischemic Brain. J Med Chem 2025; 68:5382-5399. [PMID: 40014579 DOI: 10.1021/acs.jmedchem.4c02431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2025]
Abstract
Myeloperoxidase (MPO) contributes to the progression of ischemic damage. To fully understand MPO biology, highly sensitive and specific probes that can trace the activity of endogenous MPO fluxes are indispensable. Here, we developed two hypochlorous acid (HClO)-activated near-infrared probes to image MPO activity in a noninvasive manner. The probe MPO-NIR-II could track MPO-induced HClO in real time and in situ upon various stimuli with high sensitivity and specificity. Furthermore, MPO-NIR-II could monitor the MPO activity by in vivo fluorescence imaging and confocal laser scanning microscopy in mice with ischemic stroke. Moreover, a high-content screening system for MPO inhibitors was established by combining MPO-NIR-II with MPO-overexpressed cells and mouse brain slices with ischemic stroke, and the candidate compound AZD5904 was found to effectively attenuate ischemic brain injury. Overall, this work provides a versatile fluorescence tool that holds great promise for visualizing endogenous MPO fluxes of brain ischemia.
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Affiliation(s)
- Meiling Sun
- School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China
| | - Yuting Wang
- School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Huijun Xu
- School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Yuting Shen
- School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Bin Liu
- Department of Geriatrics, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210000, China
| | - Yuchen Ma
- School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Chenchen Jiang
- School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Supeng Wang
- The First Clinical Medical College of Nanjing Medical University, Nanjing 211166, China
| | - Qi Li
- School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Yingmei Lu
- School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China
| | - Feng Han
- School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Tingyou Li
- School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Yajuan Qin
- School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
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Lei J, Liao Z, Duan W, Li Q, Duan L, Tang H, Luo H, Huang H, Li H. Association between oxidative balance score and all-cause mortality in stroke survivors. Sci Rep 2025; 15:7628. [PMID: 40038405 PMCID: PMC11880293 DOI: 10.1038/s41598-025-91721-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 02/24/2025] [Indexed: 03/06/2025] Open
Abstract
Stroke is the second leading cause of death globally. Oxidative stress plays a critical role in the development of stroke. The Oxidative Balance Score (OBS) is a tool used to assess the combined impact of diet and lifestyle on the body's antioxidant capacity. The study included stroke survivors from the National Health and Nutrition Examination Survey (1999-2018), with a total of 1,781 participants and a median follow-up duration of 6.5 years, during which 786 participants (39.59%) died. The relationship between OBS and all-cause mortality was assessed using the Cox proportional hazards model. The results indicated that individuals in higher OBS quartiles had lower mortality rates. Specifically, patients in the fourth quartile had a 41% reduced risk of all-cause mortality compared to those in the first quartile (HR = 0.59, 95% CI = 0.42-0.84, p = 0.003). Restricted cubic spline analysis revealed a linear inverse relationship between OBS and all-cause mortality. Subgroup analysis further demonstrated that the inverse association persisted across various population subgroups. Overall, our study suggests that higher levels of OBS can reduce the risk of all-cause mortality in stroke survivors and provides new evidence for their diet and lifestyle.
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Affiliation(s)
- Jinglin Lei
- Department of Neurology, The Chenzhou Affiliated Hospital, Hengyang Medical School, The First People's Hospital of Chenzhou, University of South China, Chenzhou, 423000, Hunan, China
| | - Zhiyi Liao
- Department of Burns and Plastic Surgery, The Chenzhou Affiliated Hospital, Hengyang Medical School, The First People's Hospital of Chenzhou, University of South China, Chenzhou, 423000, Hunan, China
| | - Wentao Duan
- Department of Critical Care Medicine, The Chenzhou Affiliated Hospital, Hengyang Medical School, The First People's Hospital of Chenzhou, University of South China, Chenzhou, 423000, Hunan, China
| | - Qiuli Li
- Department of Neurology, The Chenzhou Affiliated Hospital, Hengyang Medical School, The First People's Hospital of Chenzhou, University of South China, Chenzhou, 423000, Hunan, China
| | - Lili Duan
- Translational Medicine Institute, Hengyang Medical School, The First People's Hospital of Chenzhou, University of South China, Chenzhou, 423000, China
| | - Hailiang Tang
- Department of Neurology, The Chenzhou Affiliated Hospital, Hengyang Medical School, The First People's Hospital of Chenzhou, University of South China, Chenzhou, 423000, Hunan, China
| | - Hanyao Luo
- Department of Neurology, The Chenzhou Affiliated Hospital, Hengyang Medical School, The First People's Hospital of Chenzhou, University of South China, Chenzhou, 423000, Hunan, China
| | - Hao Huang
- Department of Neurology, The Chenzhou Affiliated Hospital, Hengyang Medical School, The First People's Hospital of Chenzhou, University of South China, Chenzhou, 423000, Hunan, China
| | - Haipeng Li
- Department of Neurology, The Chenzhou Affiliated Hospital, Hengyang Medical School, The First People's Hospital of Chenzhou, University of South China, Chenzhou, 423000, Hunan, China.
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Chen Y, Lv T, Lin W, Meng T, Sui Y, Chen S. J-shaped association of neutrophil-to-lymphocyte ratio with all-cause mortality and linear association with cardiovascular mortality in stroke survivors. Front Neurol 2025; 16:1473802. [PMID: 40098686 PMCID: PMC11911178 DOI: 10.3389/fneur.2025.1473802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 02/14/2025] [Indexed: 03/19/2025] Open
Abstract
Background The correlation between systemic inflammation and stroke has been well-established. Notably, the neutrophil-to-lymphocyte ratio (NLR) has been linked to poor outcomes and increased short-term mortality in acute ischemic stroke (AIS). This study aims to explore the association between NLR and long-term mortality among stroke survivors. Methods This study analyzed data from 1,229 stroke survivors enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018. The participants were categorized according to quartiles of NLR level. Multivariate Cox regression and restricted cubic splines (RCS) were applied to evaluate the relationship between NLR and all-cause and cardiovascular disease (CVD) mortality. Results Over a median follow-up of 6.41 years, 485 deaths were recorded. After multivariate adjustment, individuals in the highest NLR quartile (Q4) demonstrated significantly higher risks of all-cause mortality (hazard ratio [HR] = 1.58, 95% confidence interval [CI]: 1.06-2.34) and CVD mortality (HR = 1.90, 95% CI: 1.07-3.37) compared to those in the lowest quartile (Q1). RCS analysis revealed a J-shaped relationship between NLR and all-cause mortality and a linear relationship with CVD mortality. Conclusion These findings suggest a J-shaped association between NLR and all-cause mortality, along with a linear relationship between NLR and CVD mortality in stroke survivors.
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Affiliation(s)
- Yiqiao Chen
- Department of Neurology, Qingtian People's Hospital, Zhejiang, China
| | - Tian Lv
- Department of Neurology, Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, China
| | - Wanyi Lin
- Department of Neurology, Qingtian People's Hospital, Zhejiang, China
| | - Tianjiao Meng
- Department of Neurology, Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, China
| | - Yi Sui
- The Fourth People's Hospital of Shenyang, China Medical University, Shenyang, China
| | - Shiqin Chen
- Department of Neurology, Yuhuan Second People's Hospital, Yuhuan, China
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Sun J, Sun Y, Ma B, Qi R, Hao X, Lv J, Shi J, Wu W, Fu X, Shi R. Mechanisms of polygalasaponin F against brain ischemia-reperfusion injury by targeting NKCC1. Exp Neurol 2025; 385:115076. [PMID: 39608559 DOI: 10.1016/j.expneurol.2024.115076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Revised: 11/01/2024] [Accepted: 11/24/2024] [Indexed: 11/30/2024]
Abstract
Stroke is a serious threat to human health and current clinical therapies remain unsatisfactory. Elevated expression of Na+-K+-2Cl- cotransporter 1 (NKCC1) following stroke can disrupt the blood-brain barrier (BBB) and result in brain edema, indicating that NKCC1 may be a potential therapeutic target for improving stroke outcomes. Polygalasaponin F (PGSF) is a triterpenoid saponin isolated from Polygala japonica Houtt, which has showed neuroprotective effects in previous studies. The present study aimed to assess the protective effects of PGSF on cerebral ischemia-reperfusion injury (CIRI) in vivo and elucidate its underlying mechanism by targeting NKCC1. Experimental results revealed that following CIRI, rats displayed neurological deficits, cerebral infarction and brain edema, concurrent with increased NKCC1 mRNA and protein expression in the cerebral tissue. Notably, the administration of PGSF at both 10 mg/kg and 20 mg/kg effectively mitigated these adverse outcomes. To explore the mechanism of PGSF, pyrosequencing was used to find that CIRI reduces the methylation of the NKCC1 promoter, while PGSF enhances it. It was thereby demonstrated that PGSF could reduce NKCC1 expression in this manner. Simultaneously, we also observed that the protein expression of DNA methyltransferase 1 (DNMT1) in the ischemic penumbra was augmented after CIRI, whereas PGSF reduced the expression of DNMT1, which was contrary to the trend of NKCC1 methylation under the treatment of PGSF. These results imply that the enhancement of NKCC1 methylation by PGSF may not be catalyzed by DNMT1 and that the reduction of NKCC1 methylation level after CIRI may not be related to DNMT1. Finally, we discovered that PGSF can decrease the leakage of the BBB and enhance the expression of the BBB structural proteins occludin and ZO-1. In conclusion, PGSF can target NKCC1 as an epigenetic target and downregulate its expression following CIRI by enhancing DNA methylation of NKCC1, thereby safeguarding the structure and function of brain tissue.
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Affiliation(s)
- Jianqi Sun
- Department of Physiology, Baotou Medical College, Baotou, Inner Mongolia 014040, China; The Second Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia 014000, China
| | - Yao Sun
- Department of Physiology, Baotou Medical College, Baotou, Inner Mongolia 014040, China
| | - Baohui Ma
- Department of Physiology, Baotou Medical College, Baotou, Inner Mongolia 014040, China
| | - Ruifang Qi
- Department of Physiology, Baotou Medical College, Baotou, Inner Mongolia 014040, China
| | - Xiaoqiong Hao
- Department of Physiology, Baotou Medical College, Baotou, Inner Mongolia 014040, China
| | - Jun Lv
- Department of Physiology, Baotou Medical College, Baotou, Inner Mongolia 014040, China
| | - Jinghua Shi
- Department of Physiology, Baotou Medical College, Baotou, Inner Mongolia 014040, China
| | - Wei Wu
- Department of Physiology, Baotou Medical College, Baotou, Inner Mongolia 014040, China
| | - Xuyang Fu
- Department of Physiology, Baotou Medical College, Baotou, Inner Mongolia 014040, China
| | - Ruili Shi
- Department of Physiology, Baotou Medical College, Baotou, Inner Mongolia 014040, China; Institute of Neuroscience, Baotou Medical College, Baotou, Inner Mongolia 014040, China.
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40
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Jiang R, Wang Z, Liu J, Li T, Lv Y, Xie C, Su C. High b-Value and Ultra-High b-Value Diffusion Weighted MRI in Stroke. J Magn Reson Imaging 2025; 61:1459-1469. [PMID: 39074845 DOI: 10.1002/jmri.29547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 05/24/2024] [Accepted: 05/24/2024] [Indexed: 07/31/2024] Open
Abstract
PURPOSE To explore the application value of high-b-value and ultra-high b-value DWI in noninvasive evaluation of ischemic infarctions. STUDY TYPE Prospective. SUBJECTS Sixty-four patients with clinically diagnosed ischemic lesions based on symptoms and DWI. FIELD STRENGTH/SEQUENCE 3.0 T/T2-weighted fast spin-echo, fluid-attenuated inversion recovery, pre-contrast T1-weighted magnetization prepared rapid gradient echo sequence, multi-b-value trace DWI and q-space sampling sequences. ASSESSMENT Lesions were segmented on standard b-value DWI (SB-DWI, 1000 s/mm2), high b-value DWI (HB-DWI, 4000 s/mm2) and ultra-high b-value DWI (UB-DWI, 10,000 s/mm2), and cumulative segmented areas were the final abnormality volumes. Normal white matter (WM) areas were obtained after binarization of segmented brain. In 47 patients, fractional anisotropy (FA) and apparent diffusion coefficients (ADCs) at b values of 1000, 4000, and 10,000 s/mm2 were extracted from symmetrical WM masks and lesion masks of contralateral WM (CWM) and lesion-side WM (LWM). STATISTICAL TESTS Wilcoxon matched-pairs signed-rank test and Pearson correlation analysis. Two-tailed P-values <0.05 were considered statistically significant. RESULTS Various signals of HB-/UB-DWI (hypo-, iso- or hyper-intensity) were observed in strokes compared with SB-DWI, and some areas with iso-intensity of SB-DWI manifested with hyper-intensity on HB-/UB-DWI. Abnormality volumes from SB-DWI were significantly smaller than those from HB-DWI and UB-DWI (10.32 ± 16.45 cm3, vs. 12.25 ± 19.71 cm3 and 11.83 ± 19.41 cm3), while no significant difference exist in volume between HB-DWI and UB-DWI (P = 0.32). In CWM, FA significantly correlated with ADC4000 and ADC10,000 (maximum r = -0.51 and -0.64), but did not significantly correlate with ADC1000 (maximum r = -0.20, P = 0.17). ADC1000 or ADC4000 of LWM not significant correlated with FA of CWM (maximum r = -0.28, P = 0.06), while ADC10,000 of LWM significantly correlated with FA of CWM (maximum r = -0.46). DATA CONCLUSION HB- and UB-DWI have potential to be supplementary tools for the noninvasive evaluation of stroke lesions in clinics. EVIDENCE LEVEL 2 TECHNICAL EFFICACY: Stage 2.
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Affiliation(s)
- Rifeng Jiang
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, China
| | - ZhenXiong Wang
- Department of Radiology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Jun Liu
- Department of Medical Imaging, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ting Li
- Department of Radiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - YanChun Lv
- Department of Medical Imaging, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Chuanmiao Xie
- Department of Medical Imaging, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Changliang Su
- Department of Medical Imaging, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
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Lu T, Huang Y, Yang J, Shao C, Wan H. Yangyin Yiqi Huoxue Decoction improves the mechanism of microglia activation against CIS-induced neuroinflammatory injury by regulating the Wnt signaling pathway. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 138:156387. [PMID: 39826286 DOI: 10.1016/j.phymed.2025.156387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Revised: 12/29/2024] [Accepted: 01/10/2025] [Indexed: 01/22/2025]
Abstract
BACKGROUND Ischemic stroke is a predominant cause of neurological disability, characterized by neuroinflammation and neuronal apoptosis. The Wnt signaling pathway plays a critical role in brain repair. Yangyin Yiqi Huoxue Decoction, a traditional Chinese herbal formula, has shown potential in alleviating neuroinflammatory injury, yet, the precise mechanism underlying its effects remains unclear. PURPOSE This study aims to explore the therapeutic efficacy of Yangyin Yiqi Huoxue Decoction on ischemic stroke and its potential mechanism of action, particularly focusing on its modulation of the Wnt signaling pathway and impact on neuroinflammation and neural stem cells activity. STUDY DESIGN AND METHODS The middle cerebral artery occlusion (MCAO) rat model and an Oxygen glucose deprivation/re-oxygenation (OGD/R) cell model were employed. In vivo experiments were conducted to investigate the therapeutic effects of the Yangyin Yiqi Huoxue Decoction at high, medium, and low dosages (3.3, 1.65, and 0.83 g/kg). The effects of Yangyin Yiqi Huoxue Decoction on neuroinflammatory cytokine levels, microglial activation, and neural stem cells proliferation and differentiation were assessed in vivo experiments. Wnt signaling components were evaluated through Quantitative Real-Time PCR and Western blot in both vivo and vitro. Additionaly, the Wnt inhibitor Dickkopf-related protein 1(DKK1) was used to confirm the pathway's involvement. RESULTS The high-dose group(3.3 g/kg) of the Yangyin Yiqi Huoxue Decoction exhibited the most pronounced therapeutic effects. Yangyin Yiqi Huoxue Decoction significantly reduced pro-inflammatory cytokine levels, inhibited microglial overactivation, and enhanced neural stem cells proliferation and differentiation. It also modulated the Wnt pathway by upregulating Wnt Family Member 3A(Wnt3a) and β-catenin, while downregulating Wnt Family Member 5A(Wnt5a) and glycogen synthase kinase-3β(GSK-3β). The inhibition of Wnt signaling by Dickkopf-related protein 1(DKK1) reversed these beneficial effects, confirming Yangyin Yiqi Huoxue Decoction 's mechanism. CONCLUSIONS Yangyin Yiqi Huoxue Decoction exerts neuroprotective effects by suppressing neuroinflammation and promoting neural-stem-cell-mediated brain repair through the Wnt signaling pathway, positioning it as a potential candidate for ischemic stroke treatment.
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Affiliation(s)
- Ting Lu
- College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China
| | - Ying Huang
- College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China
| | - Jiehong Yang
- College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China; Key Laboratory of TCM Encephalopathy of Zhejiang Province, Hangzhou, Zhejiang 310053, China
| | - Chongyu Shao
- College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China; Key Laboratory of TCM Encephalopathy of Zhejiang Province, Hangzhou, Zhejiang 310053, China.
| | - Haitong Wan
- College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China; Key Laboratory of TCM Encephalopathy of Zhejiang Province, Hangzhou, Zhejiang 310053, China.
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Zhang F, Zhao D, Zhang J. Development and validation of a prognostic nomogram for predicting poor outcomes following intravenous rt-PA in patients with acute ischemic stroke. PeerJ 2025; 13:e18937. [PMID: 40028217 PMCID: PMC11871902 DOI: 10.7717/peerj.18937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 01/14/2025] [Indexed: 03/05/2025] Open
Abstract
Background Intravenous administration of recombinant tissue plasminogen activator (rt-PA) within 4.5 h of symptom onset is a standard treatment for acute ischemic stroke (AIS). However, certain patients continue to develop unfavorable outcomes despite timely rt-PA therapy. Identifying those at high risk is essential for developing individualized care plans and establishing appropriate follow-up. Methods This retrospective study included AIS patients treated with intravenous rt-PA at 0.9 mg/kg at our center. Outcomes at three months were evaluated using the modified Rankin Scale (mRS). Patients with mRS scores ≤2 were considered to have favorable outcomes, and those with scores >2 were considered to have poor outcomes. Univariable analysis and stepwise logistic regression were used to identify independent predictors of poor prognosis, and a nomogram was subsequently developed. The model's discriminative power was assessed with area under the receiver operating characteristic curves (AUC-ROC), and its calibration was examined using calibration plots. Decision curves and clinical impact curves were applied to determine clinical utility. Results Among 392 enrolled patients, 77 had poor outcomes three months after rt-PA therapy. Fibrinogen (Fg), baseline NIHSS, and a history of hypertension emerged as independent predictors of poor prognosis. The nomogram achieved an AUC of 0.948 (95% CI [0.910-0.985]), with sensitivity of 0.900 and specificity of 0.916 in the training dataset, and an AUC of 0.959 (95% CI [0.907-1.000]), with sensitivity of 0.943 and specificity of 0.947 in the validation dataset. Calibration plots demonstrated close agreement between predicted and observed probabilities, and decision curves indicated a wide range of net benefit threshold probabilities. Conclusions This nomogram, incorporating baseline NIHSS, Fg, and a history of hypertension, accurately predicts poor three-month outcomes in AIS patients treated with intravenous rt-PA. Its ease of use may facilitate early risk stratification and assist clinicians in formulating more targeted management strategies and follow-up protocols for patients likely to experience unfavorable outcomes.
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Affiliation(s)
- Fengjiao Zhang
- Department of Neurology, Tianjin NanKai Hospital, Tianjin Medical University, Tianjin, China
- Department of Neurology, Hospital of Integrated Chinese and Western Medicine, Tianjin, China
| | - Dan Zhao
- Department of Neurology, Tianjin NanKai Hospital, Tianjin Medical University, Tianjin, China
- Department of Neurology, Hospital of Integrated Chinese and Western Medicine, Tianjin, China
| | - Jing Zhang
- Department of Neurology, Tianjin NanKai Hospital, Tianjin Medical University, Tianjin, China
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Zhu J, Lin L, Si L, Zhao H, Song H, Xu X. Urban and rural disparities in stroke prediction using machine learning among Chinese older adults. Sci Rep 2025; 15:6779. [PMID: 40000818 PMCID: PMC11861258 DOI: 10.1038/s41598-025-91157-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Accepted: 02/18/2025] [Indexed: 02/27/2025] Open
Abstract
Stroke is a significant health concern in China. Differences in stroke risk between rural and urban areas have been highlighted in prior research. However, there is a scarcity of studies on urban-rural differences in predicting stroke. This study aimed to develop stroke prediction models, and urban-rural subgroup analyses were conducted to explore disparities in determinants among middle-aged and older adults. We employed nine machine learning algorithms, namely logistic regression (LR), adaptive boosting classifier, support vector machines, extreme gradient boosting, random forest, Gaussian naive Bayes (GNB), gradient boosting machine, light gradient boosting decision machine, and K Nearest Neighbours, using data derived from 9,413 individuals aged 45 years and above obtained from the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2011 to build stroke prediction models and analyze urban-rural subgroups. In the total population, GNB (AUC = 0.76) was the best model for predicting strokes, and the ten most important variables were the time taken for repeated chair stands, the chair height from floor to seat, knee height, creatinine, complete repeated chair stands, mean corpuscular volume, platelet, uric acid, body mass index, and white blood cell. In the rural subgroup, LR and GNB (AUC = 0.76) were the best, and the ten most important variables were the time taken for repeated chair stands, creatinine, platelet, the chair height from floor to seat, knee height, complete repeated chair stands, pulse, white blood cell, maintaining semi - tandem balance statically, and uric acid. In the urban subgroup, LR (AUC = 0.67) was the best, and the ten most important variables were the time taken for repeated chair stands, mean corpuscular volume, maintaining semi - tandem balance statically, uric acid, right-hand grip strength, age, blood urea nitrogen, use of trunk, arms, legs for semi - tandem balance, number of marriages, and night sleep duration. The time taken for repeated chair stands was more critical in the stroke risk model for rural individuals. Uric acid and maintaining semi - tandem balance statically were more critical in the stroke risk model for urban individuals. Our results revealed the importance of knee height and physical function predictors for stroke and highlighted the differences in determinants between urban and rural individuals, proposing targeted stroke prevention and control strategies in different populations in terms of physical function.
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Affiliation(s)
- Jingjing Zhu
- School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Luotao Lin
- Department of Individual, Family, and Community Education, University of New Mexico, Albuquerque, USA
| | - Lei Si
- School of Health Sciences, Western Sydney University, Penrith, Australia
| | - Hailei Zhao
- School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hualing Song
- School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
| | - Xianglong Xu
- School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
- School of Translational Medicine, Monash University, Melbourne, VIC, Australia.
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Yan H, Li J, Li Y, Xian L, Tang H, Zhao X, Lu T. Personalised screening tool for early detection of sarcopenia in stroke patients: a machine learning-based comparative study. Aging Clin Exp Res 2025; 37:40. [PMID: 39979762 PMCID: PMC11842499 DOI: 10.1007/s40520-025-02945-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 01/29/2025] [Indexed: 02/22/2025]
Abstract
BACKGROUND Sarcopenia is a common complication in patients with stroke, adversely affecting recovery and increasing mortality risk. However, no standardised tool exists for its screening in this population. This study aims to identify factors influencing sarcopenia in patients with stroke, develop a risk prediction model and evaluate its predictive performance. METHODS Data from 794 patients with stroke were analysed to assess demographic and clinical characteristics. Variable selection was performed using least absolute shrinkage and selection operator (LASSO) regression, followed by multivariate regression analysis. Logistic regression (LR), random forest (RF) and XGBoost algorithms were used to construct prediction models, with the optimal model subjected to external validation. Internal validation was conducted via bootstrap resampling, and external validation involved an additional cohort of 159 patients with stroke. Model performance was assessed using the area under the curve (AUC), calibration curves and decision curve analysis (DCA). RESULTS Seven variables were identified through LASSO and multivariate regression analysis. The LR model achieved the highest AUC (0.805), outperforming the RF (0.796) and XGBoost (0.780) models. Additionally, the LR model exhibited superior accuracy, precision, recall, specificity and F1-score. External validation confirmed the LR model's robustness, with an AUC of 0.816. Calibration and DCA curves demonstrated their accuracy and clinical applicability. CONCLUSIONS A predictive model, presented as a nomogram and an online risk calculator, was developed to assess sarcopenia risk in patients with stroke. Early screening using this model may facilitate timely interventions and improve patient outcomes.
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Affiliation(s)
- Huan Yan
- School of Nursing, Zunyi Medical University, Zunyi, Guizhou, China
| | - Juan Li
- Department of Nursing, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China.
| | - Yujie Li
- School of Nursing, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Lihong Xian
- School of Nursing, Zunyi Medical University, Zunyi, Guizhou, China
| | - Huan Tang
- Department of Nursing, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China
| | - Xuejiao Zhao
- School of Nursing, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Ting Lu
- School of Nursing, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
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Liu J, Huang S. Dietary index for gut microbiota is associated with stroke among US adults. Food Funct 2025; 16:1458-1468. [PMID: 39898733 DOI: 10.1039/d4fo04649h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2025]
Abstract
Aims: Emerging evidence underscores the diet-microbiota-gut-brain axis as vital to brain health. The dietary index for gut microbiota (DI-GM), quantifying diet quality linked to gut microbiota diversity, reflects healthier gut microbiota with higher scores. Therefore, this study was designed to explore the unclear association between DI-GM and stroke. Methods: A cross-sectional analysis was conducted using data from 48 677 participants aged ≥20 years in the National Health and Nutrition Examination Survey (NHANES). Demographic and dietary data were collected, and multivariable weighted logistic regression analysis was performed to evaluate the association between the DI-GM and stroke. Additionally, restricted cubic spline (RCS), subgroup analyses, and receiver operating characteristic (ROC) curve were conducted. Results: In participants aged ≥20 years, the odds ratio (OR) was 0.96 (95% CI: 0.92-1.00, P = 0.075) in the crude model, but after adjustment, the OR was 0.93 (95% CI: 0.89-0.98, P = 0.003), while higher beneficial to gut microbiota scores were consistently associated with lower stroke prevalence with ORs of 0.87 (95% CI: 0.83-0.90, P < 0.001) in the crude model and 0.88 (95% CI: 0.83-0.93, P < 0.001) after adjustment. Among participants aged 20-29 years, no significant association was observed. For those aged ≥30 years, higher DI-GM and beneficial to gut microbiota scores were associated with lower stroke prevalence, with DI-GM showing ORs of 0.93 (95% CI: 0.89-0.97, P < 0.001) in the crude model and 0.93 (95% CI: 0.89-0.98, P = 0.003) after adjustment, and beneficial to gut microbiota scores showing ORs of 0.82 (95% CI: 0.79-0.86, P < 0.001) in the crude model and 0.88 (95% CI: 0.83-0.93, P < 0.001) after adjustment. RCS indicated a linear relationship between DI-GM and stroke. Conclusion: The DI-GM was inversely and linearly associated with stroke prevalence, particularly in adults aged 30 years and above.
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Affiliation(s)
- Jingjing Liu
- Department of Anesthesiology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200090, China.
| | - Shaoqiang Huang
- Department of Anesthesiology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200090, China.
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Ping Y, Li J, Xie L, Zhao J, Chen X, Chen D, Wang Y, Jiang C, Li X. GPNMB attenuates neuroinflammation and improves ischemic stroke via modulation of PI3K/Akt and p38 MAPK signaling pathways. Brain Res 2025; 1849:149381. [PMID: 39643105 DOI: 10.1016/j.brainres.2024.149381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 11/25/2024] [Accepted: 12/03/2024] [Indexed: 12/09/2024]
Abstract
BACKGROUND Ischemic stroke is a leading cause of disability and mortality worldwide, with limited effective treatments. Neuroinflammation plays a crucial role in the progression of ischemic brain injury. Glycoprotein nonmetastatic melanoma protein B (GPNMB) has emerged as a potential regulator of inflammation, but its role and underlying mechanisms in ischemic stroke remain largely unknown. METHODS We investigated the expression profile, functional significance, and molecular pathways of GPNMB in ischemic stroke using a mouse model of middle cerebral artery occlusion (MCAO), transcriptome sequencing, and human serum samples. The effects of GPNMB knockdown on stroke outcomes, neuroinflammation, and neuronal damage were assessed in vivo. Bioinformatic analyses and experimental validation were performed to identify the downstream signaling pathways of GPNMB. RESULTS GPNMB was highly upregulated in the ischemic brain, with its expression peaking at 3-7 days post-MCAO. Serum GPNMB levels were elevated in ischemic stroke patients and correlated with stroke severity. GPNMB knockdown exacerbated stroke outcomes, neuroinflammation, and neuronal damage. Mechanistically, GPNMB positively modulated the PI3K/Akt/GSK3β pathway while negatively regulating p38 MAPK, JNK, and ERK activation. GPNMB knockdown enhanced the expression of NF-κB, a master transcriptional regulator of inflammation. CONCLUSION GPNMB is highly upregulated in the ischemic brain and confers neuroprotection against ischemic injury by modulating neuroinflammation via the PI3K/Akt and p38 MAPK signaling pathways.
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Affiliation(s)
- Yukun Ping
- Clinical Medical College, Yangzhou University, Yangzhou 225009, China; Northern Jiangsu People's Hospital Affliated to Yangzhou University, Yangzhou 225001, China
| | - Jiyu Li
- Department of Orthopedic Oncology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China
| | - Linlin Xie
- Clinical Medical College, Yangzhou University, Yangzhou 225009, China; Northern Jiangsu People's Hospital Affliated to Yangzhou University, Yangzhou 225001, China
| | - Jie Zhao
- Clinical Medical College, Yangzhou University, Yangzhou 225009, China; Northern Jiangsu People's Hospital Affliated to Yangzhou University, Yangzhou 225001, China
| | - Xuyu Chen
- Clinical Medical College, Yangzhou University, Yangzhou 225009, China
| | - Danni Chen
- Northern Jiangsu People's Hospital Affliated to Yangzhou University, Yangzhou 225001, China
| | - Yamin Wang
- Sanquan College of Xinxiang Medical University, Xinxiang 453003, China
| | - Chao Jiang
- Northern Jiangsu People's Hospital Affliated to Yangzhou University, Yangzhou 225001, China.
| | - Xiaobo Li
- Northern Jiangsu People's Hospital Affliated to Yangzhou University, Yangzhou 225001, China.
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Pan J, Chai X, Li C, Wu Y, Ma Y, Wang S, Xue Y, Zhao Y, Chen S, Zhu X, Zhao S. Eucommia ulmoides Oliv. Bark Extracts Alleviate MCAO/Reperfusion-Induced Neurological Dysfunction by Suppressing Microglial Inflammation in the Gray Matter. Int J Mol Sci 2025; 26:1572. [PMID: 40004043 PMCID: PMC11855810 DOI: 10.3390/ijms26041572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 02/05/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
Ischemic stroke ranks as the second leading cause of global mortality. The limited time for effective thrombolytic treatment has prompted the exploration of alternative prevention approaches. Eucommia ulmoides (E. ulmoides) Oliv. bark has shown multiple pharmacological effects, including neuroprotection, anti-inflammation and autophagy modulation. This study aims to elucidate the neuroprotective effects of water extract of E. ulmoides (WEU) supplementation in a middle cerebral artery occlusion (MCAO) mouse model and to further explore the underlying molecular mechanisms. Seven bioactive compounds in WEU-aucubin, chlorogenic acid, geniposidic acid, quercetin, protocatechuic acid, betulin and pinoresinol diglucoside-were identified using HPLC-MS. Our results showed that WEU supplementation significantly decreased infarct volume and ameliorated neurological dysfunction in mice following MCAO/reperfusion (MCAO/R) injury. Furthermore, the administration of WEU significantly attenuated microglia activation induced by cortical ischemia in mice and inhibited the production of pro-inflammatory mediators, including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Importantly, in contrast with the vehicle group, the protein expression levels of Toll-like receptor 4 (TLR4), phospho-p38 (p-p38) and nuclear factor kappa B (NF-κB) were reduced in the WEU group. Therefore, this present study provides evidence that E. ulmoides improves neurological behaviors by suppressing neuroinflammation and inhibiting the activation of the TLR4/ p38 MAPK and NF-κB pathways in mice after ischemia, which indicates that E.ulmoides is a promising candidate for alleviating gray matter ischemic change.
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Affiliation(s)
- Jiarong Pan
- College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China; (J.P.); (Y.W.); (Y.M.); (S.W.); (Y.X.); (Y.Z.); (S.C.)
| | - Xuejun Chai
- College of Basic Medicine, Xi’an Medical University, Xi’an 710021, China;
| | - Cixia Li
- College of Life Science and Technology, Xinxiang Medical University, Xinxiang 453003, China;
| | - Yongji Wu
- College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China; (J.P.); (Y.W.); (Y.M.); (S.W.); (Y.X.); (Y.Z.); (S.C.)
| | - Yue Ma
- College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China; (J.P.); (Y.W.); (Y.M.); (S.W.); (Y.X.); (Y.Z.); (S.C.)
| | - Songlin Wang
- College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China; (J.P.); (Y.W.); (Y.M.); (S.W.); (Y.X.); (Y.Z.); (S.C.)
| | - Yuhuan Xue
- College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China; (J.P.); (Y.W.); (Y.M.); (S.W.); (Y.X.); (Y.Z.); (S.C.)
| | - Yongkang Zhao
- College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China; (J.P.); (Y.W.); (Y.M.); (S.W.); (Y.X.); (Y.Z.); (S.C.)
| | - Shulin Chen
- College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China; (J.P.); (Y.W.); (Y.M.); (S.W.); (Y.X.); (Y.Z.); (S.C.)
| | - Xiaoyan Zhu
- College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China; (J.P.); (Y.W.); (Y.M.); (S.W.); (Y.X.); (Y.Z.); (S.C.)
| | - Shanting Zhao
- College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China; (J.P.); (Y.W.); (Y.M.); (S.W.); (Y.X.); (Y.Z.); (S.C.)
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Wang C, Long Z, Wang XD, Kong YQ, Zhou LC, Jia WH, Li P, Wang J, Wang XJ, Tian T. Quantitative evaluation method of stroke association based on multidimensional gait parameters by using machine learning. Front Neuroinform 2025; 19:1544372. [PMID: 40012766 PMCID: PMC11861528 DOI: 10.3389/fninf.2025.1544372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 01/28/2025] [Indexed: 02/28/2025] Open
Abstract
Objective NIHSS for stroke is widely used in clinical, but it is complex and subjective. The purpose of the study is to present a quantitative evaluation method of stroke association based on multi-dimensional gait parameters by using machine learning. Methods 39 ischemic stroke patients with hemiplegia were selected as the stroke group and 187 healthy adults from the community as the control group. Gaitboter system was used for gait analysis. Through the labeling of stroke patients by clinicians with NIHSS score, all gait parameters obtained were used to select appropriate gait parameters. By using machine learning algorithm, a discriminant model and a hierarchical model were trained. Results The discriminant model was used to distinguish between healthy people and stroke patients. The overall detection accuracy of the model based on KNN, SVM and Randomforest algorithms is 92.86, 92.86 and 90.00%, respectively. The hierarchical model was used to judge the severity of stroke in stroke patients. The model based on Randomforest, SVM and AdaBoost algorithm had an overall detection accuracy of 71.43, 85.71 and 85.71%, respectively. Conclusion The proposed stroke association quantitative evaluation method based on multi-dimensional gait parameters has the characteristics of high accuracy, objectivity, and quantification.
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Affiliation(s)
- Cheng Wang
- Jinan Zhougke Ubiquitous-Intelligent Institute of Computing Technology, Jinan, China
- Shandong Academy of Intelligent Computing Technology, Shandong Institutes of Industrial Technology (SDIIT), Jinan, China
- Ningbo Institute of Information Technology Application CAS, Ningbo, China
| | - Zhou Long
- Jinan Zhougke Ubiquitous-Intelligent Institute of Computing Technology, Jinan, China
- Shandong Academy of Intelligent Computing Technology, Shandong Institutes of Industrial Technology (SDIIT), Jinan, China
| | - Xiang-Dong Wang
- Bejing Key Laboratory of Mobile Computing and Pervasive Device, Beijing, China
- Institute of Computing Technology (ICT) Chinese Academy of Sciences (CAS), Beijing, China
| | - You-Qi Kong
- Department of Neurology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Li-Chun Zhou
- Department of Neurology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Wei-Hua Jia
- Department of Neurology, Beijing Shijingshan Hospital, Shijingshan Teaching Hospital of Capital Medical University, Beijing, China
| | - Pei Li
- General Practice Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Jing Wang
- General Practice Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Xiao-Juan Wang
- General Practice Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Tian Tian
- General Practice Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
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Ma C, Ge J, Han Y. Global Rounds: Advancing Cardiovascular Health in China. Circulation 2025; 151:340-342. [PMID: 39509705 DOI: 10.1161/circulationaha.124.071544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 11/05/2024] [Indexed: 11/15/2024]
Affiliation(s)
- Changsheng Ma
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, China (C.M.)
| | - Junbo Ge
- Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, China (J.G.)
| | - Yaling Han
- General Hospital of Northern Theater Command, Shenyang, China (Y.H.)
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50
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Ke C, Anand SS, Smith EE, Schulze KM, Moody A, Lear S, Poirier P, Dummer T, Desai D, Thayalasuthan V, Yusuf S, Teo KK, Wielgosz A, Lee D. Covert Vascular Brain Injury and Cognitive Dysfunction Among Chinese Adults Living in Canada and China: The CAHHM and PURE-MIND Studies. Neurology 2025; 104:e210246. [PMID: 39787476 DOI: 10.1212/wnl.0000000000210246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 11/27/2024] [Indexed: 01/12/2025] Open
Abstract
BACKGROUND AND OBJECTIVE It is unclear whether variation in covert cerebrovascular disease prevalence is attributable to ethnic differences or to other factors. We aimed to examine the associations of country of residence with covert vascular brain injury (VBI) and cognitive dysfunction among Chinese adults residing in Canada and China. METHODS This was a multisite cross-sectional study of Chinese adults aged 40-80 years in the Canadian Alliance for Healthy Hearts and Healthy Minds (CAHHM; January 1, 2014, to December 31, 2018) and Prospective Urban Rural Epidemiological-Mind (PURE-MIND; November 1, 2010, to July 31, 2015) cohorts living in Canada and China. The exposure was country of residence. The co-primary outcomes were covert VBI (defined as MRI findings of high white matter hyperintensities or covert brain infarct) and cognitive dysfunction (defined as a Montreal Cognitive Assessment [MoCA] score <26). We used generalized linear models to describe the association between country of residence and each outcome, adjusting for selected covariates. RESULTS We included 884 adults living in Canada (mean age 57.3 years, 55.4% female) and 473 living in China (mean age 56.8 years, 60.3% female). Participants in Canada had a lower prevalence of covert VBI (age 65-79 years: male, 11.5%; female, 12.2%) than those living in China (age 65-79 years: male, 62.9%; female, 52.1%). Prevalence of MoCA score <26 was lower among men and women in Canada (age 65-79 years: 40.2% and 30.0%, respectively) than among men and women in China (age 65-79 years: 74.3% and 79.2%). Living in China was associated with a 6-fold increase in the odds of covert VBI (5.85, 4.06-8.45), which remained significant after covariate adjustment. Living in China was associated with a 7-fold increase in the odds of MoCA score <26 (6.98, 5.38-9.04), which was no longer significant after covariate adjustment. DISCUSSION Despite sharing a similar ethnicity, the prevalence of covert VBI and cognitive dysfunction varied substantially by country of residence. Disparities in cognitive dysfunction were completely explained by differences in education and traditional cerebrovascular risk factors, whereas disparities in covert VBI prevalence were only partially explained by differences in such factors, suggesting a role for other environmental factors.
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Affiliation(s)
- Calvin Ke
- Department of Medicine, University of Toronto, Canada
| | - Sonia S Anand
- Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada
| | - Eric E Smith
- Department of Clinical Neurosciences, University of Calgary, Canada
| | - Karleen M Schulze
- Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada
| | - Alan Moody
- Department of Medical Imaging, University of Toronto, Canada
| | - Scott Lear
- Faculty of Health Sciences, Simon Fraser University, Vancouver, Canada
| | - Paul Poirier
- Québec Heart and Lung Institute, Université Laval, Quebec City, Canada
| | - Trevor Dummer
- School of Population and Public Health, University of British Columbia, Vancouver, Canada
| | - Dipika Desai
- Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada
| | - Vivekanandan Thayalasuthan
- Department of Medical Imaging, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Canada; and
| | - Salim Yusuf
- Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada
| | - Koon Kang Teo
- Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada
| | | | - Douglas Lee
- Department of Medicine, University of Toronto, Canada
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