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Loggini A, Hornik J, Henson J, Wesler J, Hornik A. Association between neutrophil-to-lymphocyte ratio and hematoma expansion in spontaneous intracerebral hemorrhage: A systematic review and meta-analysis. World J Crit Care Med 2025; 14:99445. [DOI: 10.5492/wjccm.v14.i2.99445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 12/02/2024] [Accepted: 12/16/2024] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND Hematoma expansion (HE) typically portends a poor prognosis in spontaneous intracerebral hemorrhage (ICH). Several radiographic and laboratory values have been proposed as predictive markers of HE.
AIM To perform a systematic review and meta-analysis on the association of neutrophil-to-lymphocyte ratio (NLR) and HE in ICH. A secondary outcome examined was the association of NLR and perihematomal (PHE) growth.
METHODS Three databases were searched (PubMed, EMBASE, and Cochrane) for studies evaluating the effect of NLR on HE and PHE growth. The inverse variance method was applied to estimate an overall effect for each specific outcome by combining weighted averages of the individual studies’ estimates of the logarithm odds ratio (OR). Given heterogeneity of the studies, a random effect was applied. Risk of bias was analyzed using the Newcastle-Ottawa Scale. The study was conducted following the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. The protocol was registered in PROSPERO (No. CRD42024549924).
RESULTS Eleven retrospective cohort studies involving 2953 patients were included in the meta-analysis. Among those, HE was investigated in eight studies, whereas PHE growth was evaluated in three. Blood sample was obtained on admission in ten studies, and at 24 hours in one study. There was no consensus on cut-off value among the studies. NLR was found to be significantly associated with higher odds of HE (OR = 1.09, 95%CI: 1.04-1.15, I2 = 86%, P < 0.01), and PHE growth (OR = 1.28, 95%CI: 1.19-1.38, I2 = 0%, P < 0.01). Qualitative analysis of each outcome revealed overall moderate risk of bias mainly due to lack of control for systemic confounders.
CONCLUSION The available literature suggests that a possible association may exist between NLR on admission and HE, and PHE growth. Future studies controlled for systemic confounders should be designed to consolidate this finding. If confirmed, NLR could be added as a readily available and inexpensive biomarker to identify a subgroup of patients at higher risk of developing HE.
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Affiliation(s)
- Andrea Loggini
- Brain and Spine Institute, Southern Illinois Healthcare, Carbondale, IL 62901, United States
- Southern Illinois University School of Medicine, Carbondale, IL 62901, United States
| | - Jonatan Hornik
- Brain and Spine Institute, Southern Illinois Healthcare, Carbondale, IL 62901, United States
- Southern Illinois University School of Medicine, Carbondale, IL 62901, United States
| | - Jessie Henson
- Brain and Spine Institute, Southern Illinois Healthcare, Carbondale, IL 62901, United States
| | - Julie Wesler
- Brain and Spine Institute, Southern Illinois Healthcare, Carbondale, IL 62901, United States
| | - Alejandro Hornik
- Brain and Spine Institute, Southern Illinois Healthcare, Carbondale, IL 62901, United States
- Southern Illinois University School of Medicine, Carbondale, IL 62901, United States
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Wang H, Li Y, Ye F, Deng Z, Huang K, Li G, Chen Y, Liu Y, Zhou L. Clinical value of inflammatory indices in predicting poor prognosis and post-hemorrhagic hydrocephalus in patients with intraventricular hemorrhage. BMC Neurol 2025; 25:115. [PMID: 40108520 PMCID: PMC11921687 DOI: 10.1186/s12883-025-04137-0] [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: 02/06/2024] [Accepted: 03/14/2025] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND Hemorrhagic stroke has a high mortality and disability rate. Among them, intraventricular hemorrhage (IVH) is an important factor leading to adverse outcomes. IVH can induce acute obstructive hydrocephalus and chronic communicating hydrocephalus. However, there are currently no effective predictive factors for the early prediction of post-hemorrhage hydrocephalus (PHH). OBJECTIVES To assess the role of inflammatory indicators in predicting PHH and poor prognostic outcomes in patients with ventricular hemorrhage. DESIGN Single center retrospective case-control study. METHODS We retrospectively examined IVH patients treated at our institution from April 2017 to March 2022. Patient characteristics, laboratory data, imaging findings, and 3-month follow-up results were recorded and analyzed. RESULTS Among the 145 patients included in the analysis, 102 eventually developed adverse outcomes. There were significant differences between patients with good and poor prognosis in terms of age at admission, GCS score, prevalence of hypertension, lymphocyte count, albumin level, red blood cell distribution width, neutrophil count, NLR, PLR, NAR, PIV, and SII; in addition, among the 110 surviving patients, 36 eventually developed posthemorrhagic hydrocephalus within 3 months. Multivariate logistic regression showed that age and NAR are independent predictors of poor prognosis in IVH patients, while albumin is an independent predictor of posthemorrhagic hydrocephalus within 3 months. CONCLUSION The NLR and NAR are independent risk factors for poor prognosis in IVH patients. Additionally, albumin is an independent predictor of chronic hydrocephalus development within 3 months in IVH patients. The NLR, NAR and albumin level could provide prognostic information about IVH patients.
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Affiliation(s)
- Haoxiang Wang
- Department of Neurosurgery, West China Medical School, West China Hospital, Sichuan University, Chengdu, China
| | - Yuanyou Li
- Department of Pediatric Neurosurgery, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Feng Ye
- Department of Neurosurgery, West China Medical School, West China Hospital, Sichuan University, Chengdu, China
| | - Ziang Deng
- Department of Neurosurgery, West China Medical School, West China Hospital, Sichuan University, Chengdu, China
| | - Keru Huang
- Department of Neurosurgery, West China Medical School, West China Hospital, Sichuan University, Chengdu, China
| | - Gaowei Li
- Department of Neurosurgery, West China Medical School, West China Hospital, Sichuan University, Chengdu, China
| | - Yaxing Chen
- Department of Neurosurgery, West China Medical School, West China Hospital, Sichuan University, Chengdu, China
| | - Yi Liu
- Department of Neurosurgery, West China Medical School, West China Hospital, Sichuan University, Chengdu, China
| | - Liangxue Zhou
- Department of Neurosurgery, West China Medical School, West China Hospital, Sichuan University, Chengdu, China.
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Gong Y, Li H, Cui H, Gong Y. Microglial Mechanisms and Therapeutic Potential in Brain Injury Post-Intracerebral Hemorrhage. J Inflamm Res 2025; 18:2955-2973. [PMID: 40026311 PMCID: PMC11872102 DOI: 10.2147/jir.s498809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 02/13/2025] [Indexed: 03/05/2025] Open
Abstract
Intracerebral hemorrhage (ICH) is a particularly common public health problem with a high mortality and disability rate and no effective treatments to enhance clinical prognosis. The increased aging population, improved vascular prevention, and augmented use of antithrombotic agents have collectively contributed to the rise in ICH incidence over the past few decades. The exploration and understanding of mechanisms and intervention strategies has great practical significance for expanding treatments and improving prognosis of ICH. Microglia, as resident macrophages of central nervous system, are responsible for the first immune defense post-ICH. After ICH, M1 microglia is firstly activated by primary injury and thrombin; subsequently, reactive microglia can further amplify the immune response and exert secondary injury (eg, oxidative stress, neuronal damage, and brain edema). The pro-inflammatory phenotype transmits to M2 microglia within 7 days post-ICH, which plays a key role in erythrophagocytosis and limiting the inflammatory secondary injury. Microglial M2 polarization has significant implications for improving prognosis, this process can be mediated through crosstalk with other cells, metabolic changes, and microbiota interaction. Clarifying the effect, timing, and potential downstream effects of multiple mechanisms that synergistically trigger anti-inflammatory responses may be necessary for clinical translation. Analyses of such intricate interaction between microglia cells and brain injury/repair mechanisms will contribute to our understanding of the critical microglial responses to microenvironment and facilitating the discovery of appropriate intervention strategies. Here, we present a comprehensive overview of the latest evidences on microglial dynamics following ICH, their role in driving primary/secondary injury mechanisms as well as neurorepair/plasticity, and possible treatment strategies targeting microglia.
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Affiliation(s)
- Yuhua Gong
- School of Smart Health, Chongqing Polytechnic University of Electronic Technology, Chongqing, 401331, People’s Republic of China
- Ultrasound Department of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China
| | - Hui Li
- School of Smart Health, Chongqing Polytechnic University of Electronic Technology, Chongqing, 401331, People’s Republic of China
| | - Huanglin Cui
- School of Smart Health, Chongqing Polytechnic University of Electronic Technology, Chongqing, 401331, People’s Republic of China
| | - Yuping Gong
- Ultrasound Department of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China
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Zhu H, Cha F, Guo T, Sang C. Outcomes, neurological function, and inflammation indices following minimally invasive hematoma removal in hypertensive cerebral hemorrhage patients. Am J Transl Res 2025; 17:1510-1521. [PMID: 40092114 PMCID: PMC11909517 DOI: 10.62347/nqyu7306] [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: 11/20/2024] [Accepted: 01/26/2025] [Indexed: 03/19/2025]
Abstract
OBJECTIVE To evaluate the clinical efficacy of minimally invasive removal of intracranial hematoma (MIRICH) in the treatment of patients with hypertensive intracranial hemorrhage (HICH) and its effect on brain nerve function and body inflammation index. METHODS This retrospective study involved 150 HICH patients treated at Shanghai Blue Cross Brain Hospital from January 2019 to March 2024. Patients were assigned into two groups according to the surgical approach they received: the control group (n = 75), treated with traditional craniotomy, and the observation group (n = 75), treated with MIRICH. The two groups were compared in terms of operative parameters, hematoma clearance rate, clinical efficacy, neurological function recovery, inflammatory markers, and postoperative complications. Risk factors affecting clinical efficacy were also analyzed. RESULTS Compared to the control group, the observation group had significantly shorter operation and hospitalization times, less intraoperative blood loss, and a higher hematoma clearance rate (P < 0.05). The total effective rate was significantly higher in observation group than that in control group (94.67% vs. 84.00%; χ2 = 4.478, P = 0.034). Three months after operation, compared to the control group, the neurological deficit score and NIH Stroke Assessment Scale (NIHSS) scale score were significantly lower in the observation group. The Activity of Daily Living Scale (ADL) scale score was significantly higher in the observation group. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and high sensitivity C-reactive protein (hs-CRP) were significantly lower in the observation group (P < 0.05). The mean velocity (Vm), peak systolic velocity (PSV) and pulsatility index (PI) in the observation group were significantly higher (P < 0.05). The cognitive function score of observation group was significantly higher than that of control group (24.65±3.13 vs. 18.43±2.76; t = 12.919, P < 0.05). The incidence of postoperative complications was 12.00% in the observation group and 17.33% in the control group, with no significant difference (P > 0.05). Multivariate Logistic regression analysis identified age, surgical method, and operation time as significant risk factors affecting clinical efficacy. CONCLUSION MIRICH surgery can improve the hematoma clearance rate in HICH patients, with better clinical efficacy, and less trauma. Additionally, it promotes neurological function recovery, improves the prognosis and living ability of patients, and reduces the level of serum inflammatory factors. It is a promising treatment option worthy of wider adoption.
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Affiliation(s)
- Haidong Zhu
- Department of NICU, Shanghai Blue Cross Brain Hospital Shanghai 201101, China
| | - Feng Cha
- Department of NICU, Shanghai Blue Cross Brain Hospital Shanghai 201101, China
| | - Tong Guo
- Department of NICU, Shanghai Blue Cross Brain Hospital Shanghai 201101, China
| | - Chenyang Sang
- Department of NICU, Shanghai Blue Cross Brain Hospital Shanghai 201101, China
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Yao J, Dai X, Yv X, Zheng L, Zheng J, Kuang B, Teng W, Yu W, Li M, Cao H, Zou W. The role of potential oxidative biomarkers in the prognosis of intracerebral hemorrhage and the exploration antioxidants as possible preventive and treatment options. Front Mol Biosci 2025; 12:1541230. [PMID: 39967652 PMCID: PMC11832355 DOI: 10.3389/fmolb.2025.1541230] [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: 12/09/2024] [Accepted: 01/15/2025] [Indexed: 02/20/2025] Open
Abstract
Intracerebral hemorrhage (ICH) is a non traumatic hemorrhage that occurs in a certain part of the brain. It usually leads to brain cell damage. According to a large number of experimental research, oxidative stress is an important pathophysiological processes of cerebral hemorrhage. In this paper, we aim to determine how changes in oxidative stress biomarkers indicate the damage degree of cerebral hemorrhage, and to explore and summarize potential treatments or interventions. We found that patients with cerebral hemorrhage are characterized by increased levels of oxidative stress markers, such as total malondialdehyde (MDA), F2 isoprostaglandin, hydroxynonenal, myeloperoxidase and protein hydroxyl. Therefore, the changes of oxidative stress caused by ICH on these markers can be used to evaluate and diagnose ICH, predict its prognosis, and guide preventive treatment to turn to antioxidant based treatment as a new treatment alternative.
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Affiliation(s)
- Jiayong Yao
- First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Xiaohong Dai
- First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Xueping Yv
- First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Lei Zheng
- Key Laboratory of Clinical Molecular Biology of Integrated Traditional Chinese and Western Medicine in Heilongjiang Province, Harbin, Heilongjiang, China
| | - Jia Zheng
- First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Binglin Kuang
- Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Wei Teng
- First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Weiwei Yu
- First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Mingyue Li
- First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Hongtao Cao
- First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Wei Zou
- First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
- Key Laboratory of Clinical Molecular Biology of Integrated Traditional Chinese and Western Medicine in Heilongjiang Province, Harbin, Heilongjiang, China
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Xia X, Liu J, Cui J, You Y, Huang C, Li H, Zhang D, Ren Q, Jiang Q, Meng X. A nomogram incorporating CT-based peri-hematoma radiomics features to predict functional outcome in patients with intracerebral hemorrhage. Eur J Radiol 2025; 183:111871. [PMID: 39662425 DOI: 10.1016/j.ejrad.2024.111871] [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: 08/28/2024] [Revised: 11/22/2024] [Accepted: 12/02/2024] [Indexed: 12/13/2024]
Abstract
OBJECTIVE To evaluate the ability of non-contrast computed tomography based peri-hematoma and intra-hematoma radiomic features to predict the 90-day poor functional outcome for spontaneous intracerebral hemorrhage (sICH) and to present an effective clinically relevant machine learning system to assist in prognosis prediction. MATERIALS AND METHODS We retrospectively analyzed the data of 691 patients diagnosed with sICH at two medical centers. Fifteen radiomic features from the intra- and peri-hematoma regions were extracted and selected to build six radiomics models. The clinical-semantic model and nomogram model were constructed to compare prediction abilities. The areas under the curve (AUC) and decision curve analysis were used to evaluate discriminative performance. RESULTS Combining radiomics of the intra-hematoma with peri-hematoma regions significantly improved the AUC to 0.843 compared with radiomics of the intra-hematoma region (AUC = 0.780, P ＜ 0.001) in the test set. A similar trend was observed in the external validation cohort (AUC, 0.769 vs. 0.793, P = 0.709). The nomogram, which integrates clinical-semantic signatures with intra-hematoma and peri-hematoma radiomics signatures, accurately predicted a 90-day poor functional outcome in both the test and external validation sets (AUC 0.879 and 0.901, respectively). CONCLUSION The nomogram constructed using clinical-semantic signatures and combined intra-hematoma and peri-hematoma radiomics signatures showed the potential to precisely predict 90-day poor functional outcomes for sICH.
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Affiliation(s)
- Xiaona Xia
- Department of Radiology, Qilu Hospital (Qingdao) of Shandong University, Qingdao, China
| | - Jieqiong Liu
- Department of Radiology, Qilu Hospital (Qingdao) of Shandong University, Qingdao, China
| | - Jiufa Cui
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yi You
- Department of Research Collaboration, R&D Center, Beijing Deepwise & League of PHD Technology Co., Ltd, Beijing 100080, China
| | - Chencui Huang
- Department of Research Collaboration, R&D Center, Beijing Deepwise & League of PHD Technology Co., Ltd, Beijing 100080, China
| | - Hui Li
- Department of Radiology, Qilu Hospital (Qingdao) of Shandong University, Qingdao, China
| | - Daiyong Zhang
- Department of Radiology, Qilu Hospital (Qingdao) of Shandong University, Qingdao, China
| | - Qingguo Ren
- Department of Radiology, Qilu Hospital (Qingdao) of Shandong University, Qingdao, China
| | - Qingjun Jiang
- Department of Radiology, Qilu Hospital (Qingdao) of Shandong University, Qingdao, China
| | - Xiangshui Meng
- Department of Radiology, Qilu Hospital (Qingdao) of Shandong University, Qingdao, China.
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Wang X, Lin X, Chen Z, Long H, Zhou X, Lei S, Liu J, Dong H, Liu F, Hu H, Guo C. Annao Pingchong decoction attenuates oxidative stress and neuronal apoptosis following intracerebral hemorrhage via RAGE-NOX2/4 axis. Front Neurosci 2024; 18:1491343. [PMID: 39737434 PMCID: PMC11683131 DOI: 10.3389/fnins.2024.1491343] [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: 09/04/2024] [Accepted: 12/03/2024] [Indexed: 01/01/2025] Open
Abstract
Background Intracerebral hemorrhage (ICH) is a severe condition associated with high mortality and disability rates. Oxidative stress plays a critical role in the development of secondary brain injury (SBI) following ICH. Previous research has demonstrated that Annao Pingchong decoction (ANPCD) treatment for ICH has antioxidant effects, but the exact mechanism is not yet fully understood. Objective This study aimed to investigate the neuroprotective effects of ANPCD on oxidative stress and neuronal apoptosis after ICH by targeting the receptor for advanced glycation end products (RAGE)-NADPH oxidase (NOX) 2/4 signaling axis. Methods The research involved the creation of rat ICH models, the mNSS assay to assess neurological function, Nissl staining to evaluate neuronal damage, and biochemical assays to measure oxidative and antioxidant levels. The expression of RAGE-NOX2/4 axis proteins was analyzed using western blotting and immunofluorescence, while neuronal apoptosis was assessed with TUNEL staining. Furthermore, after performing quality control of drug-containing serum using UPLC-MS/MS, we employed an in vitro model of heme-induced injury in rat cortical neurons to investigate the neuroprotective mechanisms of ANPCD utilizing RAGE inhibitors. Results The findings indicated that ANPCD improved neurological deficits, reduced neuronal damage, decreased ROS and MDA levels, and increased the activities enzymatic activities of SOD, CAT, GSH and GPX. Additionally, it suppressed the RAGE-NOX2/4 signaling axis and neuronal apoptosis. Conclusion ANPCD exhibits neuroprotective effects by inhibiting the RAGE-NOX2/4 signaling axis, thereby alleviating neuronal oxidative stress and apoptosis following ICH.
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Affiliation(s)
- Xu Wang
- Experiment Center of Medical Innovation, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
- Department of Neurology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Xiaoyuan Lin
- Experiment Center of Medical Innovation, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Zilin Chen
- Department of Pediatrics, Guang’anmen Hospital, China Academy of Traditional Chinese Medicine, Beijing, China
| | - Hongping Long
- Experiment Center of Medical Innovation, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Xuqing Zhou
- Experiment Center of Medical Innovation, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Shihui Lei
- Experiment Center of Medical Innovation, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Jian Liu
- Experiment Center of Medical Innovation, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Huan Dong
- Experiment Center of Medical Innovation, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Fang Liu
- Experiment Center of Medical Innovation, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Hua Hu
- Department of Neurology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Chun Guo
- Experiment Center of Medical Innovation, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
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Lopez Arrieta Z, Rodríguez-Cavallo E, Méndez-Cuadro D. Gingival Enlargement Associated with Orthodontics Appliance Increases Protein Carbonylation and Alters Phosphorylation of Salivary Proteome. Dent J (Basel) 2024; 12:208. [PMID: 39056995 PMCID: PMC11275265 DOI: 10.3390/dj12070208] [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: 04/02/2024] [Revised: 05/19/2024] [Accepted: 06/20/2024] [Indexed: 07/28/2024] Open
Abstract
Gingival enlargement is a common clinical sign in the gingival diseases associated with orthodontic treatment. Its biological mechanisms are not completely understood; nevertheless, the biochemical changes associated with these inflammatory and overgrowth processes could alter the post-translational protein modifications occurring in various locations within the mouth. Here, changes in the profiles of the carbonylated and phosphorylated proteins in saliva were examined in donors with gingival enlargement (seven men and seven women) and healthy donors (six men and eight women). The sociodemographic characteristics of both groups did not present significant differences. Carbonylation was measured by a quantitative immunoassay (Dot Blot), whereas the profiles of the phosphorylated proteins were visualized by SDS-PAGE with quercetin staining. Some phosphopeptides were also identified using a typical LC-MS-MS approach. Our results showed that gingival enlargement induced a significant increase in oxidative damage in salivary proteins. While a significant reduction in phosphorylation was observed at the stain level in SDS-PAGE, there was a slight increase in the number of phosphorylated proteins identified by MS in samples with gingival enlargement.
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Affiliation(s)
| | - Erika Rodríguez-Cavallo
- Analytical Chemistry and Biomedicine Group, Exacts and Natural Sciences Faculty, University of Cartagena, Cartagena 130014, Colombia;
| | - Darío Méndez-Cuadro
- Analytical Chemistry and Biomedicine Group, Exacts and Natural Sciences Faculty, University of Cartagena, Cartagena 130014, Colombia;
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Xu M, Wang J, Zhan C, Zhou Y, Luo Z, Yang Y, Zhu D. Association of follow-up neutrophil-to-lymphocyte ratio and systemic inflammation response index with stroke-associated pneumonia and functional outcomes in cerebral hemorrhage patients: a case-controlled study. Int J Surg 2024; 110:4014-4022. [PMID: 38498385 PMCID: PMC11254209 DOI: 10.1097/js9.0000000000001329] [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: 12/19/2023] [Accepted: 03/03/2024] [Indexed: 03/20/2024]
Abstract
BACKGROUND The neutrophil-to-lymphocyte ratio (NLR) and systemic inflammation response index (SIRI) at admission are independent diagnostic biomarkers in stroke-associated pneumonia (SAP). Our study aimed to investigate the association between NLR, SIRI, specifically follow-up NLR and SIRI, and SAP, as well as their relationship with functional outcomes. PATIENTS AND METHODS We retrospectively included 451 consecutive intracerebral hemorrhage patients from May 2017 to May 2019. We conducted univariate and multivariable analyses to identify the factors independently associated with SAP and poor functional outcomes. RESULTS Compared to 127 (28.16%) patients diagnosed with SAP, those without SAP had both lower baseline and follow-up NLR and SIRI values ( P <0.001). After adjustments, we found that baseline NLR [OR, 1.039 (95% CI, 1.003-1.077); P =0.036] and follow-up NLR [OR, 1.054 (95% CI, 1.011-1.098); P =0.012] were independently associated with SAP. The follow-up NLR was also associated with a higher mRS [OR, 1.124 (95% CI, 1.025-1.233); P =0.013] and lower ADL-MBI score [OR, 1.167 (95% CI, 1.057-1.289); P =0.002] at discharge. Multivariable analysis indicated that advanced age and nasogastric tube feeding were independently associated with SAP ( P <0.05). We constructed a dynamic nomogram to identify SAP risk. Further subgroup analysis revealed that baseline NLR [OR, 1.062 (95% CI, 1.007-1.120); P =0.026] is independently associated with SAP in the nasogastric feeding group, while follow-up NLR [OR, 1.080 (95% CI, 1.024-1.139); P =0.005] was associated with the occurrence of SAP in non-nasogastric feeding patients. CONCLUSIONS We found elevated baseline and follow-up NLR values were associated with SAP occurrence, and increasing follow-up NLR indicated poor functional outcomes. Inflammatory markers at different stages may offer individualized guidance for patients receiving various treatments.
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Affiliation(s)
- Mengmeng Xu
- Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University
| | - Jingru Wang
- Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University
| | - Chenyi Zhan
- Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University
| | - Ying Zhou
- Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University
| | - Zhixian Luo
- Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University
| | - Yunjun Yang
- Department of Nuclear Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China
| | - Dongqin Zhu
- Department of Nuclear Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China
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Mao Y, Huang L, Ji G, Wang L, Wang X, Zheng X. Neutrophil-to-lymphocyte ratio on admission predicts early perihematomal edema growth after intracerebral hemorrhage. Medicine (Baltimore) 2024; 103:e37585. [PMID: 38518026 PMCID: PMC10957013 DOI: 10.1097/md.0000000000037585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 02/22/2024] [Indexed: 03/24/2024] Open
Abstract
Poor functional outcome is associated with perihematomal edema (PHE) expansion after intracerebral hemorrhage (ICH). The inflammatory response is crucial for the onset and progression of PHE. This study aimed to determine the connection between admission neutrophil-lymphocyte ratio (NLR) and early PHE development. We retrospectively analyzed patients with ICH admitted to the Chaohu Affiliated Hospital of Anhui Medical University from January 2021 to December 2022. The primary outcome measure was absolute PHE, defined as the volume of the follow-up PHE minus admission PHE. A semiautomated measurement tool (3D Slicer) was used to calculate the volumes of cerebral hematoma and cerebral edema. Spearman's correlation analysis determined the relationship between NLR and absolute PHE. The multiple linear regression model was constructed to analyze the predictive relation of admission NLR on early PHE expansion. A total of 117 patients were included. The median hematoma and PHE volumes on admission were 9.38 mL (interquartile range [IQR], 4.53-19.54) and 3.54 mL (IQR, 1.33-7.1), respectively. The median absolute PHE was 2.26 mL (IQR, 1.25-4.23), and the median NLR was 3.10 (IQR, 2.26-3.86). Spearman's correlation test showed a positive correlation between admission NLR and absolute PHE (r = .548, P < .001). Multiple linear regression analyses suggested that for every 1-unit increase in admission NLR (B = .176, SE = .043, Beta = .275, P < .001), there was a 0.176 mL increase in absolute PHE. Admission neutrophil-to-lymphocyte ratio (NLR) significantly and positively predicted early perihematomal edema (PHE) expansion.
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Affiliation(s)
- Yirong Mao
- Department of Neurosurgery, The Chaohu Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Lumao Huang
- Department of Neurosurgery, The Chaohu Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Gengsheng Ji
- Department of Radiology, The Chaohu Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Liang Wang
- Department of Neurosurgery, The Chaohu Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Xiang Wang
- Department of Neurosurgery, The Chaohu Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Xinyi Zheng
- Department of Neurosurgery, The Chaohu Affiliated Hospital of Anhui Medical University, Hefei, China
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Li Q, Huang L, Ding Y, Sherchan P, Peng W, Zhang JH. Recombinant Slit2 suppresses neuroinflammation and Cdc42-mediated brain infiltration of peripheral immune cells via Robo1-srGAP1 pathway in a rat model of germinal matrix hemorrhage. J Neuroinflammation 2023; 20:249. [PMID: 37899442 PMCID: PMC10613398 DOI: 10.1186/s12974-023-02935-2] [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: 03/22/2023] [Accepted: 10/17/2023] [Indexed: 10/31/2023] Open
Abstract
BACKGROUND Germinal matrix hemorrhage (GMH) is a devastating neonatal stroke, in which neuroinflammation is a critical pathological contributor. Slit2, a secreted extracellular matrix protein, plays a repulsive role in axon guidance and leukocyte chemotaxis via the roundabout1 (Robo1) receptor. This study aimed to explore effects of recombinant Slit2 on neuroinflammation and the underlying mechanism in a rat model of GMH. METHODS GMH was induced by stereotactically infusing 0.3 U of bacterial collagenase into the germinal matrix of 7-day-old Sprague Dawley rats. Recombinant Slit2 or its vehicle was administered intranasally at 1 h after GMH and daily for 3 consecutive days. A decoy receptor recombinant Robo1 was co-administered with recombinant Slit2 after GMH. Slit2 siRNA, srGAP1 siRNA or the scrambled sequences were administered intracerebroventricularly 24 h before GMH. Neurobehavior, brain water content, Western blotting, immunofluorescence staining and Cdc42 activity assays were performed. RESULTS The endogenous brain Slit2 and Robo1 expressions were increased after GMH. Robo1 was expressed on neuron, astrocytes and infiltrated peripheral immune cells in the brain. Endogenous Slit2 knockdown by Slit2 siRNA exacerbated brain edema and neurological deficits following GMH. Recombinant Slit2 (rSlit2) reduced neurological deficits, proinflammatory cytokines, intercellular adhesion molecules, peripheral immune cell markers, neuronal apoptosis and Cdc42 activity in the brain tissue after GMH. The anti-neuroinflammation effects were reversed by recombinant Robo1 co-administration or srGAP1 siRNA. CONCLUSIONS Recombinant Slit2 reduced neuroinflammation and neuron apoptosis after GMH. Its anti-neuroinflammation effects by suppressing onCdc42-mediated brain peripheral immune cells infiltration was at least in part via Robo1-srGAP1 pathway. These results imply that recombinant Slit2 may have potentials as a therapeutic option for neonatal brain injuries.
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Affiliation(s)
- Qian Li
- Department of Pediatrics, Army Medical Center, Army Medical University, 10 Changjiang Access Rd, Yuzhong District, Chongqing, 400042, China
- Women and Children's Hospital of Chongqing Medical University, 120 Longshan Access Rd, Yubei District, Chongqing, 400010, China
| | - Lei Huang
- Department of Physiology and Pharmacology, School of Medicine, Loma Linda University, 11041 Campus Street, Loma Linda, CA, 92354, USA
- Department of Neurosurgery, School of Medicine, Loma Linda University, 11234 Anderson Street, Loma Linda, CA, 92354, USA
| | - Yan Ding
- Department of Physiology and Pharmacology, School of Medicine, Loma Linda University, 11041 Campus Street, Loma Linda, CA, 92354, USA
| | - Prativa Sherchan
- Department of Physiology and Pharmacology, School of Medicine, Loma Linda University, 11041 Campus Street, Loma Linda, CA, 92354, USA
| | - Wenjie Peng
- Department of Pediatrics, Army Medical Center, Army Medical University, 10 Changjiang Access Rd, Yuzhong District, Chongqing, 400042, China
| | - John H Zhang
- Department of Physiology and Pharmacology, School of Medicine, Loma Linda University, 11041 Campus Street, Loma Linda, CA, 92354, USA.
- Department of Neurosurgery, School of Medicine, Loma Linda University, 11234 Anderson Street, Loma Linda, CA, 92354, USA.
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Nie S, Wang H, Liu Q, Tang Z, Tao W, Wang N. Prognostic value of neutrophils to lymphocytes and platelets ratio for 28-day mortality in patients with acute respiratory distress syndrome: a retrospective study. BMC Pulm Med 2022; 22:314. [PMID: 35971101 PMCID: PMC9376578 DOI: 10.1186/s12890-022-02112-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 08/08/2022] [Indexed: 11/24/2022] Open
Abstract
Background Acute respiratory distress syndrome (ARDS) is a rapidly progressive and fatal respiratory failure disease that often occurs in critically ill patients. Since ARDS is associated with immune dysregulation and coagulation abnormalities, it is necessary to identify an appropriate predictor that can accurately predict ARDS mortality based on its pathophysiology. Therefore, this study aimed to evaluate the clinical value of neutrophils to lymphocytes and platelets ratio (N/LPR) in predicting 28-day mortality in ARDS patients.
Methods From July 2018 to October 2021, the medical records of ARDS patients were retrospective reviewed. Neutrophil count, lymphocyte count, and platelet count were collected, and the neutrophil-to-lymphocyte ratio (NLR) and N/LPR were calculated. Multivariate logistic regression analyses were performed to identify independent predictors of 28-day mortality in ARDS. Receiver operating characteristic (ROC) curve with the area under curve (AUC) was used to evaluate optimal cut-off values for 28-day mortality in ARDS. Kaplan–Meier analysis was used to estimate the 28-day survival probabilities stratified by optimal cut-off values of N/LPR and NLR. Results A total of 136 ARDS patients were included in this study and were further divided into survivors (n = 69) and non-survivors (n = 67) groups according to their survival status on day 28. There were no significant differences between the two groups in age, sex, history of smoking and drinking, comorbidities, and reasons of admission (P > 0.05). Non-survivors had significantly higher neutrophil counts, NLR and N/LPR and had significantly lower platelet counts than survivors (P < 0.05). Multivariate regression analysis revealed that N/LPR, NLR and platelet counts were independent predictors for 28-day mortality in ARDS (P < 0.05). The ROC analyses showed that N/LPR with optimal cut-off value of 10.57 (sensitivity: 74.6%; specificity: 72.5%) is a more reliable predictor for 28-day mortality in ARDS than NLR and platelet count (AUC: 0.785 vs. 0.679 vs. 0.326). Further subgroup analysis confirmed that ARDS patients with N/LPR < 10.57 had significantly lower 28-day mortality than patients with N/LPR ≥ 10.57 (P < 0.001). Kaplan–Meier analysis also confirmed that ARDS patients with N/LPR < 10.57 had significantly longer survival. Conclusion N/LPR is an independent risk factor associated with 28-day mortality in ARDS patients and shows better performance in predicting mortality rate than NLR.
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Affiliation(s)
- Shiyu Nie
- Department of Critical Care Medicine, Yongchuan Hospital, Chongqing Medical University, No. 439 Xuanhua Road, Yongchuan District, Chongqing, 402160, China
| | - Hongjin Wang
- Department of Critical Care Medicine, Yongchuan Hospital, Chongqing Medical University, No. 439 Xuanhua Road, Yongchuan District, Chongqing, 402160, China
| | - Qiuyu Liu
- Department of Critical Care Medicine, Yongchuan Hospital, Chongqing Medical University, No. 439 Xuanhua Road, Yongchuan District, Chongqing, 402160, China
| | - Ze Tang
- Department of Critical Care Medicine, Yongchuan Hospital, Chongqing Medical University, No. 439 Xuanhua Road, Yongchuan District, Chongqing, 402160, China
| | - Wu Tao
- Department of Critical Care Medicine, Yongchuan Hospital, Chongqing Medical University, No. 439 Xuanhua Road, Yongchuan District, Chongqing, 402160, China
| | - Nian Wang
- Department of Critical Care Medicine, Yongchuan Hospital, Chongqing Medical University, No. 439 Xuanhua Road, Yongchuan District, Chongqing, 402160, China.
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