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Guo X, Guo L, Lu QZ, Xie H, Chen J, Su WL, Tian Y, Li XH, Miao HL, Zhang Y, Yang Y, Liao C, Deng JY, Yang YH, Tang CL, Liu HJ. Effect of electroacupuncture combined with Tuina therapy on gut microbiota in patients with knee osteoarthritis. World J Gastroenterol 2025; 31:105495. [DOI: 10.3748/wjg.v31.i18.105495] [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: 02/18/2025] [Revised: 03/14/2025] [Accepted: 04/21/2025] [Indexed: 05/13/2025] Open
Abstract
BACKGROUND Knee osteoarthritis (KOA) is a chronic condition characterized by joint pain and dysfunction, driven by aging and obesity. Research indicates that the gut microbiota significantly influences KOA, potentially affecting inflammation and disease progression through the gut-joint axis. Traditional treatments like non-steroidal anti-inflammatory drugs offer symptom relief but have adverse effects. Emerging therapies like electroacupuncture (EA) and Tuina (TN) have shown promise in alleviating pain and improving joint function by targeting the gut microbiota.
AIM To clarify the efficacy of EA with TN in treating KOA and its effect on gut microbiota regulation.
METHODS Sixty patients with KOA were allocated to EA or EA + TN (ET) group (n = 30 each). Seven acupoints were punctured. The ET group received TN after each EA session. Both groups completed 12 sessions. The visual analog scale (VAS) for assessing pain and the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) for measuring pain intensity, joint stiffness, and functional capacity were employed to assess clinical outcomes. Pre- and post-treatment fecal specimens underwent 16S ribosomal RNA sequencing to analyze the gut microbiota.
RESULTS The ET group showed higher rates of “effective” and “markedly effective” outcomes. The VAS score of the ET group remained significantly lower than that of the EA group (P < 0.001) immediately after treatment and 1 week post-treatment. The total WOMAC score (P < 0.001), pain (P = 0.191), stiffness (P = 0.015), and function scores (P < 0.001) decreased significantly in the ET group post-treatment. The gut microbiota analysis revealed no significant changes in alpha diversity in either group. Beta-diversity analysis indicated distinct patterns in the ET group before and after treatment. Significant changes in microbial abundance were detected in both groups, highlighting variations in Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes.
CONCLUSION ET outperforms EA alone in improving KOA pain, stiffness, and function, potentially via gut microbiota modulation, intestinal barrier protection, and inflammation reduction.
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Affiliation(s)
- Xiao Guo
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China
- Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing Medical University, Chongqing 400016, China
| | - Liang Guo
- Department of Jinshang, Chongqing Orthopedic Hospital of Traditional Chinese Medicine, Chongqing 400012, China
| | - Qing-Ze Lu
- Department of Jinshang, Chongqing Orthopedic Hospital of Traditional Chinese Medicine, Chongqing 400012, China
| | - Hui Xie
- Department of Jinshang, Chongqing Orthopedic Hospital of Traditional Chinese Medicine, Chongqing 400012, China
| | - Juan Chen
- Department of Jinshang, Chongqing Orthopedic Hospital of Traditional Chinese Medicine, Chongqing 400012, China
| | - Wen-Li Su
- Department of Jinshang, Chongqing Orthopedic Hospital of Traditional Chinese Medicine, Chongqing 400012, China
| | - Yuan Tian
- Department of Jinshang, Chongqing Orthopedic Hospital of Traditional Chinese Medicine, Chongqing 400012, China
| | - Xiao-Hua Li
- Department of Jinshang, Chongqing Orthopedic Hospital of Traditional Chinese Medicine, Chongqing 400012, China
| | - Hong-Lei Miao
- Department of Jinshang, Chongqing Orthopedic Hospital of Traditional Chinese Medicine, Chongqing 400012, China
| | - Yi Zhang
- Department of Jinshang, Chongqing Orthopedic Hospital of Traditional Chinese Medicine, Chongqing 400012, China
| | - Yan Yang
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China
- Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing Medical University, Chongqing 400016, China
| | - Cai Liao
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China
- Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing Medical University, Chongqing 400016, China
| | - Jun-Yuan Deng
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China
- Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing Medical University, Chongqing 400016, China
| | - Yun-Hao Yang
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China
- Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing Medical University, Chongqing 400016, China
| | - Cheng-Lin Tang
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China
- College of Acupuncture and Tuina, Chongqing University of Chinese Medicine, Chongqing 402760, China
| | - He-Jing Liu
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China
- Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing Medical University, Chongqing 400016, China
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Lu J, Shi Z, Geng L, Ren D, Hou H, Ren G, Yao S, Wang P. Transcriptional Analysis Reveals That the FHL1/JAK-STAT Pathway is Involved in Acute Cartilage Injury in Mice. Cartilage 2025:19476035251323601. [PMID: 40119525 PMCID: PMC11948231 DOI: 10.1177/19476035251323601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/24/2025] Open
Abstract
ObjectiveThis study aimed to identify genes and signaling pathways associated with acute cartilage injury using RNA sequencing (RNA-seq).MethodsKnee joint cartilage samples were collected from normal mice and 2 models of acute cartilage injury (non-invasive and groove models) within an 8-hour time limit. RNA-seq revealed differential gene expression between the injury models and controls, with subsequent validation using real-time quantitative polymerase chain reaction (RT-qPCR) for 9 representative genes.ResultsCompared to controls, the non-invasive model showed 36 differentially expressed genes (DEGs) (13 up-regulated, 23 down-regulated), with Gm14648 and Gm35438 showing the most significant upregulation and downregulation, respectively. The groove model exhibited 255 DEGs (13 up-regulated, 23 down-regulated), with Gm14648 and Gm35438 showing the (222 up-regulated, 33 down-regulated). Six overlapping genes were identified between the non-invasive and groove models, including up-regulated genes (Igfn1, Muc6, Hmox1) and down-regulated genes (Pthlh, Cyp1a1, Gm13490), validated by RT-qPCR. Gene ontology (GO) analysis highlighted involvement in environmental information processing and cartilage organ system function, while Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis implicated the JAK-STAT signaling pathway. RT-qPCR and immunohistochemistry confirmed downregulation of Fhl1 in the non-invasive model, supported by Western blotting of p-JAK2/t-JAK2 levels.ConclusionsThis study identifies DEGs (13 up-regulated, 23 down-regulated), with Gm14648 and Gm35438 showing the in acute cartilage injury, suggesting potential therapeutic targets. The role of Fhl1 in cartilage protection via the JAK-STAT pathway warrants further investigation in acute cartilage injury research.
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Affiliation(s)
- Jian Lu
- Department of Orthopedic Surgery, Orthopedic Research Institute of Hebei Province, Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China
| | - Zhenhua Shi
- Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang, People’s Republic of China
| | - Lindan Geng
- Department of Orthopedic Surgery, Orthopedic Research Institute of Hebei Province, Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China
| | - Dong Ren
- Department of Orthopedic Surgery, Orthopedic Research Institute of Hebei Province, Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China
- Orthopedic Research Institute of Hebei Province, Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China
| | - Haowei Hou
- Orthopedic Research Institute of Hebei Province, Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China
| | - Guowei Ren
- Department of Orthopedic Surgery, Orthopedic Research Institute of Hebei Province, Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China
| | - Shuangquan Yao
- Department of Orthopedic Surgery, Orthopedic Research Institute of Hebei Province, Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China
- Orthopedic Research Institute of Hebei Province, Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China
| | - Pengcheng Wang
- Department of Orthopedic Surgery, Orthopedic Research Institute of Hebei Province, Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China
- Orthopedic Research Institute of Hebei Province, Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China
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Ning P, Lin S, Shi Y, Liu T. Potential role of gut-related factors in the pathology of cartilage in osteoarthritis. Front Nutr 2025; 11:1515806. [PMID: 39845920 PMCID: PMC11753001 DOI: 10.3389/fnut.2024.1515806] [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: 10/23/2024] [Accepted: 12/19/2024] [Indexed: 01/24/2025] Open
Abstract
Osteoarthritis (OA) is a common progressive degenerative disease. Gut microbiota (GM) and their metabolites have been closely associated with the onset, progression, and pathology of OA. GM and their metabolites may influence the cartilage directly, or indirectly by affecting the gut, the immune system, and the endocrine system. They function through classical pathways in cartilage metabolism and novel pathways that have recently been discovered. Some of them have been used as targets for the prevention and treatment of OA. The current study sought to describe the major pathological signaling pathways in OA chondrocytes and the potential role of gut-related factors in these pathways.
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Affiliation(s)
- Peng Ning
- Department of Pediatric Orthopaedics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Shuting Lin
- Department of Pediatric Orthopaedics, Shengjing Hospital of China Medical University, Shenyang, China
- Department of Pediatric Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yongyan Shi
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Tianjing Liu
- Department of Pediatric Orthopaedics, Shengjing Hospital of China Medical University, Shenyang, China
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Yang J, Zhou P, Xu T, Bo K, Zhu C, Wang X, Chang J. Identification of biomarkers related to tryptophan metabolism in osteoarthritis. Biochem Biophys Rep 2024; 39:101763. [PMID: 39040542 PMCID: PMC11261530 DOI: 10.1016/j.bbrep.2024.101763] [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: 12/21/2023] [Revised: 04/17/2024] [Accepted: 06/21/2024] [Indexed: 07/24/2024] Open
Abstract
Background OA (osteoarthritis) is a common joint disease characterized by damage to the articular cartilage and affects the entire joint tissue, with its main manifestations being joint pain, stiffness, and limited movement.Currently,we know that OA is a complex process composed of inflammatory and metabolic factors.It is reported that the occurrence and development of OA is related to the change of tryptophan metabolism.Therefore, the study of tryptophan metabolism and OA related genes is hopeful to find a new therapeutic target for OA. Methods Differentially expressed genes (DEGs) in GSE55235 were gained via differential expression analysis (OA samples vs normal samples). The tryptophan metabolic related DEGs (TMR-DEGs) were obtained by overlapping tryptophan metabolism related genes (TMRGs) and DEGs. Further, biomarkers were screening via Least absolute shrinkage and selection operator (LASSO), naive bayes (NB) and supportvector machine-recursive feature elimination (SVM-RFE) algorithm to establish a diagnostic model. Afterward, Gene Set Enrichment Analysis (GSEA) and drug prediction were performed based on diagnostic biomarkers by multiple software and databases. Eventually, expression level of biomarker public databases was verified using real-time quantitative polymerase chain reaction (RT-qPCR). Results Three tryptophan metabolism related biomarkers (TDO2, AOX1 and SLC3A2) were identified in OA. GSEA analysis demonstrated that biomarkers were associated with the function of 'FoxO signaling pathway', 'spliceosome' and 'ribosome'. There were seven drugs with therapeutic potential on TDO2 and AOX1. Ultimately, compared with normal group, expression of AOX1 and SLC3A2 in OA group remarkable lower. Conclusion Overall, three tryptophan metabolic related diagnostic biomarkers that associated with OA were obtained, which provided a original direction for the diagnosis and treatment of OA.
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Affiliation(s)
- Junjun Yang
- Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Orthopaedics, Anhui Public Health Clinical Center, Hefei, China
| | - Ping Zhou
- Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Orthopaedics, Anhui Public Health Clinical Center, Hefei, China
| | - Tangbing Xu
- Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Orthopaedics, Anhui Public Health Clinical Center, Hefei, China
| | - Kaida Bo
- Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Orthopaedics, Anhui Public Health Clinical Center, Hefei, China
| | - Chenxin Zhu
- Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Orthopaedics, Anhui Public Health Clinical Center, Hefei, China
| | - Xu Wang
- Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Orthopaedics, Anhui Public Health Clinical Center, Hefei, China
| | - Jun Chang
- Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Orthopaedics, Anhui Public Health Clinical Center, Hefei, China
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Zhu H, Yang X, Zhao Y. Recent Advances in Current Uptake Situation, Metabolic and Nutritional Characteristics, Health, and Safety of Dietary Tryptophan. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:6787-6802. [PMID: 38512048 DOI: 10.1021/acs.jafc.3c06419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/22/2024]
Abstract
Tryptophan (Trp) is an essential amino acid which is unable to be synthesized in the body. Main sources of Trp are uptake of foods such as oats and bananas. In this review, we describe the status of current dietary consumption, metabolic pathways and nutritional characteristics of Trp, as well as its ingestion and downstream metabolites for maintaining body health and safety. This review also summarizes the recent advances in Trp metabolism, particularly the 5-HT, KYN, and AhR activation pathways, revealing that its endogenous host metabolites are not only differentially affected in the body but also are closely linked to health. More attention should be paid to targeting its specific metabolic pathways and utilizing food molecules and probiotics for manipulating Trp metabolism. However, the complexity of microbiota-host interactions requires further exploration to precisely refine targets for innovating the gut microbiota-targeted diagnostic approaches and informing subsequent studies and targeted treatments of diseases.
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Affiliation(s)
- Haoyan Zhu
- Key Laboratory of the Ministry of Education for Medicinal Resource and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi'an 710119, China
| | - Xingbin Yang
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China
| | - Yan Zhao
- Key Laboratory of the Ministry of Education for Medicinal Resource and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi'an 710119, China
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Marchese L, Contartese D, Giavaresi G, Di Sarno L, Salamanna F. The Complex Interplay between the Gut Microbiome and Osteoarthritis: A Systematic Review on Potential Correlations and Therapeutic Approaches. Int J Mol Sci 2023; 25:143. [PMID: 38203314 PMCID: PMC10778637 DOI: 10.3390/ijms25010143] [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: 11/07/2023] [Revised: 12/18/2023] [Accepted: 12/20/2023] [Indexed: 01/12/2024] Open
Abstract
The objective of this review is to systematically analyze the potential correlation between gut microbiota and osteoarthritis (OA) as well as to evaluate the feasibility of microbiota-targeted therapies for treating OA. Studies conducted from October 2013 to October 2023 were identified via a search on electronic databases such as PubMed, Web of Science, and Scopus, following established PRISMA statement standards. Two reviewers independently screened, assessed, and extracted relevant data, and then they graded the studies using the ROBINS I tool for non-randomized interventions studies and SYRCLE's risk-of-bias tool for animal studies. A search through 370 studies yielded 38 studies (24 preclinical and 14 clinical) that were included. In vivo research has predominantly concentrated on modifying the gut microbiota microenvironment, using dietary supplements, probiotics, and prebiotics to modify the OA status. Lactobacilli are the most thoroughly examined with Lactobacillus acidophilus found to effectively reduce cartilage damage, inflammatory factors, and pain. Additionally, Lactobacillus M5 inhibits the development of OA by preventing high-fat diet (HFD)-induced obesity and protecting cartilage from damage. Although there are limited clinical studies, certain compositions of intestinal microbiota may be associated with onset and progression of OA, while others are linked to pain reduction in OA patients. Based on preclinical studies, there is evidence to suggest that the gut microbiota could play a significant role in the development and progression of OA. However, due to the scarcity of clinical studies, the exact mechanism linking the gut microbiota and OA remains unclear. Further research is necessary to evaluate specific gut microbiota compositions, potential pathogens, and their corresponding signaling pathways that contribute to the onset and progression of OA. This will help to validate the potential of targeting gut microbiota for treating OA patients.
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Affiliation(s)
| | | | - Gianluca Giavaresi
- Surgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy; (L.M.); (D.C.); (L.D.S.); (F.S.)
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Liao Z, Han X, Wang Y, Shi J, Zhang Y, Zhao H, Zhang L, Jiang M, Liu M. Differential Metabolites in Osteoarthritis: A Systematic Review and Meta-Analysis. Nutrients 2023; 15:4191. [PMID: 37836475 PMCID: PMC10574084 DOI: 10.3390/nu15194191] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 09/08/2023] [Accepted: 09/12/2023] [Indexed: 10/15/2023] Open
Abstract
(1) Many studies have attempted to utilize metabolomic approaches to explore potential biomarkers for the early detection of osteoarthritis (OA), but consistent and high-level evidence is still lacking. In this study, we performed a systematic review and meta-analysis of differential small molecule metabolites between OA patients and healthy individuals to screen promising candidates from a large number of samples with the aim of informing future prospective studies. (2) Methods: We searched the EMBASE, the Cochrane Library, PubMed, Web of Science, Wan Fang Data, VIP Date, and CNKI up to 11 August 2022, and selected relevant records based on inclusion criteria. The risk of bias was assessed using the Newcastle-Ottawa quality assessment scale. We performed qualitative synthesis by counting the frequencies of changing directions and conducted meta-analyses using the random effects model and the fixed-effects model to calculate the mean difference and 95% confidence interval. (3) Results: A total of 3798 records were identified and 13 studies with 495 participants were included. In the 13 studies, 132 kinds of small molecule differential metabolites were extracted, 58 increased, 57 decreased and 17 had direction conflicts. Among them, 37 metabolites appeared more than twice. The results of meta-analyses among four studies showed that three metabolites increased, and eight metabolites decreased compared to healthy controls (HC). (4) Conclusions: The main differential metabolites between OA and healthy subjects were amino acids (AAs) and their derivatives, including tryptophan, lysine, leucine, proline, phenylalanine, glutamine, dimethylglycine, citrulline, asparagine, acetylcarnitine and creatinine (muscle metabolic products), which could be potential biomarkers for predicting OA.
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Affiliation(s)
- Zeqi Liao
- Medical Experimental Center, China Academy of Chinese Medical Sciences, Beijing 100700, China; (Z.L.); (Y.W.); (J.S.); (Y.Z.); (H.Z.)
| | - Xu Han
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China;
| | - Yuhe Wang
- Medical Experimental Center, China Academy of Chinese Medical Sciences, Beijing 100700, China; (Z.L.); (Y.W.); (J.S.); (Y.Z.); (H.Z.)
| | - Jingru Shi
- Medical Experimental Center, China Academy of Chinese Medical Sciences, Beijing 100700, China; (Z.L.); (Y.W.); (J.S.); (Y.Z.); (H.Z.)
| | - Yuanyue Zhang
- Medical Experimental Center, China Academy of Chinese Medical Sciences, Beijing 100700, China; (Z.L.); (Y.W.); (J.S.); (Y.Z.); (H.Z.)
| | - Hongyan Zhao
- Medical Experimental Center, China Academy of Chinese Medical Sciences, Beijing 100700, China; (Z.L.); (Y.W.); (J.S.); (Y.Z.); (H.Z.)
| | - Lei Zhang
- National Data Center of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China;
| | - Miao Jiang
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China;
| | - Meijie Liu
- Medical Experimental Center, China Academy of Chinese Medical Sciences, Beijing 100700, China; (Z.L.); (Y.W.); (J.S.); (Y.Z.); (H.Z.)
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