Pub Date : 2025-07-01DOI: 10.1016/j.joim.2025.05.004
Yan Han , Yu Wang , Mo-yi Shi , Yu Liu , Xiao-dong Cheng , Yang Zhou
Objective
The concept of constitution in traditional Chinese medicine (TCM) has been increasingly recognized as a crucial factor in both the prevention and treatment of insomnia. However, rigorous statistical evidence on the correlation between TCM constitutions—particularly mixed constitutions—and insomnia disorder remains limited. This study aimed to investigate the association between specific TCM constitutions and insomnia disorder.
Methods
A cross-sectional study was conducted at the Department of Preventive Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, from November 2022 to December 2023. TCM constitutions were assessed using the Constitution in Chinese Medicine Questionnaire. Insomnia disorder was diagnosed by experienced internal medicine physicians according to the criteria of the International Classification of Sleep Disorders, Third Edition. A total of 1065 eligible participants (242 with insomnia disorder and 823 controls) were included in the final analysis.
Results
Among the participants, 862 (80.94%) exhibited biased constitutions, with 75.30% of these having mixed constitutions. Logistic regression analysis revealed a negative association between the gentleness constitution and insomnia disorder, whereas qi-deficiency, yang-deficiency, phlegm-dampness and qi-depression constitutions were positively associated with insomnia disorder. These associations remained significant after adjusting for potential confounders and were further validated through sensitivity analysis using propensity score matching.
Conclusion
Significant associations between TCM constitutions and insomnia disorder were demonstrated. Future research should further investigate these relationships and explore the underlying mechanisms through rigorous longitudinal and interventional studies to improve understanding and clinical applications.
Please cite this article as: Han Y, Wang Y, Shi MY, Liu Y, Cheng XD, Zhou Y. Integrating traditional Chinese medicine constitutions into insomnia management: Findings from a cross-sectional study. J Integr Med. 2025; 23(4): 382–389.
{"title":"Integrating traditional Chinese medicine constitutions into insomnia management: Findings from a cross-sectional study","authors":"Yan Han , Yu Wang , Mo-yi Shi , Yu Liu , Xiao-dong Cheng , Yang Zhou","doi":"10.1016/j.joim.2025.05.004","DOIUrl":"10.1016/j.joim.2025.05.004","url":null,"abstract":"<div><h3>Objective</h3><div>The concept of constitution in traditional Chinese medicine (TCM) has been increasingly recognized as a crucial factor in both the prevention and treatment of insomnia. However, rigorous statistical evidence on the correlation between TCM constitutions—particularly mixed constitutions—and insomnia disorder remains limited. This study aimed to investigate the association between specific TCM constitutions and insomnia disorder.</div></div><div><h3>Methods</h3><div>A cross-sectional study was conducted at the Department of Preventive Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, from November 2022 to December 2023. TCM constitutions were assessed using the Constitution in Chinese Medicine Questionnaire. Insomnia disorder was diagnosed by experienced internal medicine physicians according to the criteria of the <em>International Classification of Sleep Disorders</em>, <em>Third Edition</em>. A total of 1065 eligible participants (242 with insomnia disorder and 823 controls) were included in the final analysis.</div></div><div><h3>Results</h3><div>Among the participants, 862 (80.94%) exhibited biased constitutions, with 75.30% of these having mixed constitutions. Logistic regression analysis revealed a negative association between the gentleness constitution and insomnia disorder, whereas qi-deficiency, yang-deficiency, phlegm-dampness and qi-depression constitutions were positively associated with insomnia disorder. These associations remained significant after adjusting for potential confounders and were further validated through sensitivity analysis using propensity score matching.</div></div><div><h3>Conclusion</h3><div>Significant associations between TCM constitutions and insomnia disorder were demonstrated. Future research should further investigate these relationships and explore the underlying mechanisms through rigorous longitudinal and interventional studies to improve understanding and clinical applications.</div><div>Please cite this article as: Han Y, Wang Y, Shi MY, Liu Y, Cheng XD, Zhou Y. Integrating traditional Chinese medicine constitutions into insomnia management: Findings from a cross-sectional study. <em>J Integr Med</em>. 2025; 23(4): 382–389.</div></div>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":"23 4","pages":"Pages 382-389"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-01DOI: 10.1016/j.joim.2025.05.001
Jia Wen Chin , Rafidah Abdullah , Benjamin Wei Wang Tan , Koh Wei Wong , Ban-Hock Khor
<div><h3>Background</h3><div>The use of complementary and alternative medicine (CAM) is common among individuals with underlying chronic illnesses.</div></div><div><h3>Objective</h3><div>This systematic review and meta-analysis investigated the global prevalence and patterns of CAM use among individuals with chronic kidney disease (CKD).</div></div><div><h3>Search strategy</h3><div>PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature Plus were searched from inception until 26th February 2024.</div></div><div><h3>Inclusion criteria</h3><div>Original articles reporting the use of at least one type of CAM among individuals aged above 18 years old and at all stages of CKD or undergoing any form of kidney replacement therapy.</div></div><div><h3>Data extraction and analysis</h3><div>Two independent reviewers performed the literature screening. The data were extracted from the included studies by one reviewer and cross-checked by another. Discrepancies were resolved by discussion and consensus among two reviewers. Primary information included prevalence of CAM use, types of CAM used, reasons for CAM use, factors associated with CAM use, and disclosure to healthcare providers. Meta-analyses were performed to determine the pooled prevalence of CAM use and non-disclosure of CAM using a random effect model.</div></div><div><h3>Results</h3><div>Forty-one studies were included in this systematic review and meta-analysis. The pooled prevalence of CAM use was 43% (95% confidence interval: 34%, 51%), <em>I</em><sup>2</sup> = 99.46%. The reasons for CAM use included treatment of underlying comorbidities, complications or symptoms, maintenance of general health, and treatment of CKD. Nutritional approaches were the most common CAM modality, with 412 different herbal and dietary supplements reported; psychological and physical approaches included massage therapy, relaxation techniques, and mind–body practices; and other complementary health approaches such as homeopathy, traditional Chinese medicine, and Ayurvedic medicine were also frequently reported. Factors associated with CAM use included sociodemographic characteristics such as older age, female gender, or higher income; disease or therapy factors such as not having diabetes, relying on hemodialysis, or poor adherence to medication; and patient or internal factors such as positive attitude towards CAM and perceived safety of CAM. About 66% (61%, 72%) of CAM users did not disclose the use of CAM to their healthcare providers.</div></div><div><h3>Conclusion</h3><div>CAM use is prevalent among individuals with CKD, and healthcare providers should communicate openly and effectively to emphasize the rational use of CAM to avoid potential harm.</div><div>Please cite this article as: Chin JW, Abdullah R, Tan BWW, Wong KW, Khor BH. Prevalence and patterns of complementary and alternative medicine usage among adults with chronic kidney disease: A systematic review and meta-analysis. <em>J Inte
背景：补充和替代医学（CAM）的使用是常见的个体与潜在的慢性疾病。目的：本系统综述和荟萃分析调查了慢性肾脏疾病（CKD）患者中CAM的全球患病率和使用模式。检索策略：检索PubMed， Embase和护理和联合健康文献累积索引Plus，从创建到2024年2月26日。纳入标准：在18岁以上CKD所有阶段或接受任何形式肾脏替代治疗的患者中至少使用一种CAM的原创文章。资料提取和分析：两位独立的审稿人进行文献筛选。数据由一位审稿人从纳入的研究中提取，并由另一位审稿人进行交叉检查。差异通过两位审稿人的讨论和共识得到解决。主要信息包括辅助手段使用的流行程度、使用的辅助手段类型、使用的原因、与辅助手段使用相关的因素以及向医疗保健提供者披露的情况。采用随机效应模型进行meta分析，以确定CAM使用和不披露的总流行率。结果：41项研究被纳入本系统综述和荟萃分析。CAM使用的总患病率为43%(95%可信区间：34%，51%),I2 = 99.46%。使用CAM的原因包括治疗潜在的合并症、并发症或症状、维持一般健康和治疗慢性肾病。营养方法是最常见的辅助治疗方式，共报告了412种不同的草药和膳食补充剂；心理和物理方法包括按摩疗法、放松技巧和身心练习；以及其他辅助保健方法，如顺势疗法、传统中医和阿育吠陀医学，也经常被报道。与辅助治疗使用相关的因素包括社会人口统计学特征，如年龄较大、女性性别或收入较高；疾病或治疗因素，如没有糖尿病，依赖血液透析，或药物依从性差；患者或内部因素，如对CAM的积极态度和认知CAM的安全性。约66%（61%,72%）的CAM使用者没有向其医疗保健提供者披露使用CAM的情况。结论：慢性肾病患者普遍使用CAM，医护人员应公开有效沟通，强调CAM的合理使用，避免潜在危害。本文署名：Chin JW， Abdullah R, Tan BWW, Wong KW, Khor BH。成人慢性肾病患者补充和替代药物使用的患病率和模式：一项系统回顾和荟萃分析集成医学[J]；打印前Epub。
{"title":"Prevalence and patterns of complementary and alternative medicine usage among adults with chronic kidney disease: A systematic review and meta-analysis","authors":"Jia Wen Chin , Rafidah Abdullah , Benjamin Wei Wang Tan , Koh Wei Wong , Ban-Hock Khor","doi":"10.1016/j.joim.2025.05.001","DOIUrl":"10.1016/j.joim.2025.05.001","url":null,"abstract":"<div><h3>Background</h3><div>The use of complementary and alternative medicine (CAM) is common among individuals with underlying chronic illnesses.</div></div><div><h3>Objective</h3><div>This systematic review and meta-analysis investigated the global prevalence and patterns of CAM use among individuals with chronic kidney disease (CKD).</div></div><div><h3>Search strategy</h3><div>PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature Plus were searched from inception until 26th February 2024.</div></div><div><h3>Inclusion criteria</h3><div>Original articles reporting the use of at least one type of CAM among individuals aged above 18 years old and at all stages of CKD or undergoing any form of kidney replacement therapy.</div></div><div><h3>Data extraction and analysis</h3><div>Two independent reviewers performed the literature screening. The data were extracted from the included studies by one reviewer and cross-checked by another. Discrepancies were resolved by discussion and consensus among two reviewers. Primary information included prevalence of CAM use, types of CAM used, reasons for CAM use, factors associated with CAM use, and disclosure to healthcare providers. Meta-analyses were performed to determine the pooled prevalence of CAM use and non-disclosure of CAM using a random effect model.</div></div><div><h3>Results</h3><div>Forty-one studies were included in this systematic review and meta-analysis. The pooled prevalence of CAM use was 43% (95% confidence interval: 34%, 51%), <em>I</em><sup>2</sup> = 99.46%. The reasons for CAM use included treatment of underlying comorbidities, complications or symptoms, maintenance of general health, and treatment of CKD. Nutritional approaches were the most common CAM modality, with 412 different herbal and dietary supplements reported; psychological and physical approaches included massage therapy, relaxation techniques, and mind–body practices; and other complementary health approaches such as homeopathy, traditional Chinese medicine, and Ayurvedic medicine were also frequently reported. Factors associated with CAM use included sociodemographic characteristics such as older age, female gender, or higher income; disease or therapy factors such as not having diabetes, relying on hemodialysis, or poor adherence to medication; and patient or internal factors such as positive attitude towards CAM and perceived safety of CAM. About 66% (61%, 72%) of CAM users did not disclose the use of CAM to their healthcare providers.</div></div><div><h3>Conclusion</h3><div>CAM use is prevalent among individuals with CKD, and healthcare providers should communicate openly and effectively to emphasize the rational use of CAM to avoid potential harm.</div><div>Please cite this article as: Chin JW, Abdullah R, Tan BWW, Wong KW, Khor BH. Prevalence and patterns of complementary and alternative medicine usage among adults with chronic kidney disease: A systematic review and meta-analysis. <em>J Inte","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":"23 4","pages":"Pages 370-381"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-01DOI: 10.1016/j.joim.2025.06.003
Xiao-jie Li , Le Chang , Yang Mi , Ge Zhang , Shan-shan Zhu , Yue-xiao Zhang , Hao-yu Wang , Yi-shuang Lu , Ye-xuan Ping , Peng-yuan Zheng , Xia Xue
Objective
Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity.
Methods
To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes.
Results
We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1.
Conclusion
We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual’s prognosis, guide precision treatments, and assist clinical decision making for HCC patients.
Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. J Integr Med. 2025; 23(4): 445–456.
目的：昼夜节律紊乱（CRD）是多种肿瘤类型中与预后不良相关的危险因素，包括肝细胞癌（HCC）。然而，其机制尚不清楚。本研究旨在基于CRD定义HCC亚型，并探讨其个体异质性。方法：采用HCC CRD评分法（HCCcrds）量化CRD。使用机器学习算法，我们在The Cancer Genome Atlas liver HCC队列（n = 369）中鉴定了CRD模块基因并定义了CRD相关的HCC亚型，并验证了该方法的稳健性。此外，我们使用生物信息学工具来研究这些CRD亚型的细胞异质性。结果：我们定义了三种不同的HCC亚型，它们在预后方面表现出显著的异质性。高HCCcrds的crd相关亚型与预后差、病理分级高、临床分期进展显著相关，而低HCCcrds的crd相关亚型具有较好的临床预后。我们还为每个亚型确定了新的生物标志物，如烟酰胺n-甲基转移酶和肉豆浆酰化富丙氨酸蛋白激酶C底物样1。结论：我们根据肝细胞癌患者的昼夜节律将其分为三组，并确定了他们的特异性生物标志物。在这些组中，HCCcrds越大，预后越差。这种方法有可能改善个体预后的预测，指导精确治疗，并协助HCC患者的临床决策。本文请注明：李晓军，常丽，米莹，张刚，朱世生，张永祥，等。综合组学分析根据昼夜节律定义肝细胞癌的亚型。集成医学[J]；打印前Epub。
{"title":"Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm","authors":"Xiao-jie Li , Le Chang , Yang Mi , Ge Zhang , Shan-shan Zhu , Yue-xiao Zhang , Hao-yu Wang , Yi-shuang Lu , Ye-xuan Ping , Peng-yuan Zheng , Xia Xue","doi":"10.1016/j.joim.2025.06.003","DOIUrl":"10.1016/j.joim.2025.06.003","url":null,"abstract":"<div><h3>Objective</h3><div>Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity.</div></div><div><h3>Methods</h3><div>To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in <em>The Cancer Genome Atlas</em> liver HCC cohort (<em>n</em> = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes.</div></div><div><h3>Results</h3><div>We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1.</div></div><div><h3>Conclusion</h3><div>We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual’s prognosis, guide precision treatments, and assist clinical decision making for HCC patients.</div><div>Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. <em>J Integr Med</em>. 2025; 23(4): 445–456.</div></div>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":"23 4","pages":"Pages 445-456"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-01DOI: 10.1016/j.joim.2025.05.003
Wan-ling Zhong , Jian-qiong Yang , Hai Liu , Ya-li Wu , Hui-juan Shen , Peng-yue Li , Shou-ying Du
Objective
EPF3 is a fibrinolysin monomer isolated and purified from Pheretima vulgaris Chen, an earthworm used in traditional Chinese medicine as Dilong for treating blood stasis syndrome. Its composition, anticoagulant and fibrinolytic activities, and relevant mechanisms have been confirmed through in vitro experiments. However, whether it has antithrombotic effects in vivo and can be absorbed by the gastrointestinal tract is unknown. This study evaluates the antithrombotic effect in zebrafish and investigates the gastrointestinal stability and intestinal absorption mechanism of this protein in vitro.
Methods
The antithrombotic effect of EPF3 in vivo was verified using the zebrafish thrombus model induced by arachidonic acid and FeCl3. Then, the protein bands of EPF3 incubated with simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and homogenate of Caco-2 cells (HC2C) were analyzed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis to evaluate its gastrointestinal stability. Finally, the transport behavior and absorption mechanism of EPF3 were studied using Caco-2 cell monolayer.
Results
EPF3 could significantly enhance the returned blood volume and blood flow velocity in zebrafish with platelet aggregation thrombus induced by arachidonic acid. It could also prolong the formation time of tail artery thrombus and increase the blood flow velocity in zebrafish with vessel injury thrombus induced by FeCl3. EPF3 was stable in SIF and HC2C and unstable in SGF. The permeability of EPF3 in Caco-2 monolayer was time-dependent and concentration-dependent. The efflux ratio was less than 1.2 during transport, and the transport behavior was not affected by inhibitors. EPF3 could reversibly reduce the expression of tight junction-related proteins, including zonula occludens-1, occludin, and claudin-1 in Caco-2 cells.
Conclusion
EPF3 could play a thrombolytic and antithrombotic role in zebrafish. It could be transported and absorbed into the intestine through cellular bypass pathway by opening the intestinal epithelium tight junction. This study provides a scientific explanation for the antithrombotic effect of earthworm and provides a basis for the feasibility of subsequent development of EPF3 as an antithrombotic enteric-soluble preparation.
Please cite this article as: Zhong WL, Yang JQ, Liu H, Wu YL, Shen HJ, Li PY, Du SY. Antithrombotic effect in zebrafish of a fibrinolytic protein EPF3 from Dilong (Pheretima vulgaris Chen) and its transport mechanism in Caco-2 monolayer through cell bypass pathway. J Integr Med. 2025; 23(4): 415–428.
{"title":"Antithrombotic effect in zebrafish of a fibrinolytic protein EPF3 from Dilong (Pheretima vulgaris Chen) and its transport mechanism in Caco-2 monolayer through cell bypass pathway","authors":"Wan-ling Zhong , Jian-qiong Yang , Hai Liu , Ya-li Wu , Hui-juan Shen , Peng-yue Li , Shou-ying Du","doi":"10.1016/j.joim.2025.05.003","DOIUrl":"10.1016/j.joim.2025.05.003","url":null,"abstract":"<div><h3>Objective</h3><div>EPF3 is a fibrinolysin monomer isolated and purified from <em>Pheretima vulgaris</em> Chen<em>,</em> an earthworm used in traditional Chinese medicine as Dilong for treating blood stasis syndrome. Its composition, anticoagulant and fibrinolytic activities, and relevant mechanisms have been confirmed through in vitro experiments. However, whether it has antithrombotic effects in vivo and can be absorbed by the gastrointestinal tract is unknown. This study evaluates the antithrombotic effect in zebrafish and investigates the gastrointestinal stability and intestinal absorption mechanism of this protein in vitro.</div></div><div><h3>Methods</h3><div>The antithrombotic effect of EPF3 in vivo was verified using the zebrafish thrombus model induced by arachidonic acid and FeCl<sub>3</sub>. Then, the protein bands of EPF3 incubated with simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and homogenate of Caco-2 cells (HC2C) were analyzed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis to evaluate its gastrointestinal stability. Finally, the transport behavior and absorption mechanism of EPF3 were studied using Caco-2 cell monolayer.</div></div><div><h3>Results</h3><div>EPF3 could significantly enhance the returned blood volume and blood flow velocity in zebrafish with platelet aggregation thrombus induced by arachidonic acid. It could also prolong the formation time of tail artery thrombus and increase the blood flow velocity in zebrafish with vessel injury thrombus induced by FeCl<sub>3</sub>. EPF3 was stable in SIF and HC2C and unstable in SGF. The permeability of EPF3 in Caco-2 monolayer was time-dependent and concentration-dependent. The efflux ratio was less than 1.2 during transport, and the transport behavior was not affected by inhibitors. EPF3 could reversibly reduce the expression of tight junction-related proteins, including zonula occludens-1, occludin, and claudin-1 in Caco-2 cells.</div></div><div><h3>Conclusion</h3><div>EPF3 could play a thrombolytic and antithrombotic role in zebrafish. It could be transported and absorbed into the intestine through cellular bypass pathway by opening the intestinal epithelium tight junction. This study provides a scientific explanation for the antithrombotic effect of earthworm and provides a basis for the feasibility of subsequent development of EPF3 as an antithrombotic enteric-soluble preparation.</div><div>Please cite this article as: Zhong WL, Yang JQ, Liu H, Wu YL, Shen HJ, Li PY, Du SY. Antithrombotic effect in zebrafish of a fibrinolytic protein EPF3 from Dilong (<em>Pheretima vulgaris</em> Chen) and its transport mechanism in Caco-2 monolayer through cell bypass pathway. <em>J Integr Med</em>. 2025; 23(4): 415–428.</div></div>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":"23 4","pages":"Pages 415-428"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-01DOI: 10.1016/j.joim.2025.04.008
Chang-shun Chen , Lei Wen , Fei Yang , Yong-cheng Deng , Jian-hua Ji , Rong-jin Chen , Zhong Chen , Ge Chen , Jin-yi Gu
<div><h3>Background</h3><div>A growing body of research is exploring the role of antioxidant and anti-inflammatory dietary supplements in the treatment of osteoarthritis, highlighting an increasing emphasis on non-pharmacological interventions. Although more patients are turning to supplements to manage osteoarthritis, their actual effectiveness remains uncertain.</div></div><div><h3>Objective</h3><div>This study aims to provide a comprehensive evaluation of the available evidence concerning the efficacy of various dietary supplements in osteoarthritis treatment.</div></div><div><h3>Search strategy</h3><div>We searched PubMed, Embase, Cochrane Library and Web of Science for studies on the use of various dietary supplements in the treatment of osteoarthritis from the creation of each database until Jan 20, 2025.</div></div><div><h3>Inclusion criteria</h3><div>(1) Research object: osteoarthritis. (2) Intervention measures: patients in the treatment group received dietary supplements, while the control group received placebos. (3) Research type: randomized controlled trials (RCTs).</div></div><div><h3>Data extraction and analysis</h3><div>Two researchers independently examined the literature and retrieved data based on predefined criteria. The information gathered included the first author, year of publication, sample size, participant demographics, length of the follow-up period, intervention and control measures, and inclusion indications. RCTs comparing dietary supplements to placebo with the pain and function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) among patients with osteoarthritis were included. The optimal dietary supplement was identified based on the total ranking by summing the surface under the cumulative ranking curve (SUCRA) of these two scores. Furthermore, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to confirm the quality of the evidence.</div></div><div><h3>Results</h3><div>Overall, 23 studies covering 21 dietary supplements and involving 2455 participants met the inclusion criteria. In the WOMAC pain score, the SUCRA of passion fruit peel extract was 91% (mean difference [MD]: –9.2; 95% confidence interval [CI]: [–16.0, –2.3]), followed by methylsulfonylmethane (89%), undenatured type II collagen (87%), collagen (84%), and Lanconone (82%). The SUCRA (99%) of passion fruit peel extract (MD: –41.0; 95% CI: [–66.0, –16.0]) ranked first in terms of the WOMAC function score, followed by Lanconone (95%), collagen (86%), ParActin (84%), and <em>Lactobacillus casei</em> strain Shirota (83%). The top three total rankings are passion fruit peel extract (95.0%), Lanconone (88.5%), and collagen (85.0%). However, the GRADE revealed low evidence quality.</div></div><div><h3>Conclusion</h3><div>Passion fruit peel extract was the best supplement for improving WOMAC pain and function scores in patients with osteoarthritis, followed by Lanconone and collagen.
背景：越来越多的研究正在探索抗氧化和抗炎膳食补充剂在骨关节炎治疗中的作用，并越来越强调非药物干预。尽管越来越多的患者转而使用补充剂来治疗骨关节炎，但它们的实际效果仍不确定。目的：本研究旨在对各种膳食补充剂治疗骨关节炎的疗效进行综合评价。检索策略：我们检索了PubMed、Embase、Cochrane Library和Web of Science，从每个数据库创建到2025年1月20日，检索了各种膳食补充剂在骨关节炎治疗中的应用研究。纳入标准：(1)研究对象：骨关节炎。(2)干预措施：治疗组给予膳食补充剂，对照组给予安慰剂。(3)研究类型：随机对照试验（RCTs）。数据提取和分析：两位研究人员根据预定义的标准独立地检查文献和检索数据。收集的信息包括第一作者、发表年份、样本量、参与者人口统计、随访时间、干预和控制措施以及纳入适应症。在骨关节炎患者中，将膳食补充剂与安慰剂与西安大略省和麦克马斯特大学骨关节炎指数（WOMAC）的疼痛和功能亚量表进行比较的随机对照试验包括在内。将两项评分的累积排名曲线下曲面（SUCRA）相加，根据总排名确定最优膳食补充剂。此外，建议评估、发展和评价分级（GRADE）被用来确认证据的质量。结果：总体而言，23项研究涵盖21种膳食补充剂，涉及2455名参与者符合纳入标准。在WOMAC疼痛评分中，百香果皮提取物的SUCRA为91%(平均差值[MD]: -9.2；95%可信区间[CI]:[-16.0, -2.3])，其次是甲基磺酰甲烷（89%）、未变性II型胶原（87%）、胶原蛋白（84%）和兰康酮（82%）。百香果皮提取物的SUCRA (99%) (MD: -41.0；在WOMAC功能评分中，95% CI:[-66.0, -16.0])排名第一，其次是Lanconone（95%）、collagen（86%）、ParActin（84%）、Lactobacillus casei strain Shirota（83%）。前三名分别是百香果皮提取物（95.0%）、Lanconone（88.5%）和胶原蛋白（85.0%）。然而，GRADE显示证据质量较低。结论：百香果皮提取物是改善骨关节炎患者WOMAC疼痛和功能评分的最佳补充剂，兰康酮次之，胶原蛋白次之。然而，需要进一步大规模、设计良好的随机对照试验来证实这些有希望的发现。陈春春，文丽，杨峰，邓玉春，季建辉，陈荣军，陈志，陈刚，顾建勇。膳食补充剂对骨关节炎患者的影响：系统评价和网络meta分析。集成医学[J]；打印前Epub。
{"title":"Effects of dietary supplements on patients with osteoarthritis: A systematic review and network meta-analysis","authors":"Chang-shun Chen , Lei Wen , Fei Yang , Yong-cheng Deng , Jian-hua Ji , Rong-jin Chen , Zhong Chen , Ge Chen , Jin-yi Gu","doi":"10.1016/j.joim.2025.04.008","DOIUrl":"10.1016/j.joim.2025.04.008","url":null,"abstract":"<div><h3>Background</h3><div>A growing body of research is exploring the role of antioxidant and anti-inflammatory dietary supplements in the treatment of osteoarthritis, highlighting an increasing emphasis on non-pharmacological interventions. Although more patients are turning to supplements to manage osteoarthritis, their actual effectiveness remains uncertain.</div></div><div><h3>Objective</h3><div>This study aims to provide a comprehensive evaluation of the available evidence concerning the efficacy of various dietary supplements in osteoarthritis treatment.</div></div><div><h3>Search strategy</h3><div>We searched PubMed, Embase, Cochrane Library and Web of Science for studies on the use of various dietary supplements in the treatment of osteoarthritis from the creation of each database until Jan 20, 2025.</div></div><div><h3>Inclusion criteria</h3><div>(1) Research object: osteoarthritis. (2) Intervention measures: patients in the treatment group received dietary supplements, while the control group received placebos. (3) Research type: randomized controlled trials (RCTs).</div></div><div><h3>Data extraction and analysis</h3><div>Two researchers independently examined the literature and retrieved data based on predefined criteria. The information gathered included the first author, year of publication, sample size, participant demographics, length of the follow-up period, intervention and control measures, and inclusion indications. RCTs comparing dietary supplements to placebo with the pain and function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) among patients with osteoarthritis were included. The optimal dietary supplement was identified based on the total ranking by summing the surface under the cumulative ranking curve (SUCRA) of these two scores. Furthermore, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to confirm the quality of the evidence.</div></div><div><h3>Results</h3><div>Overall, 23 studies covering 21 dietary supplements and involving 2455 participants met the inclusion criteria. In the WOMAC pain score, the SUCRA of passion fruit peel extract was 91% (mean difference [MD]: –9.2; 95% confidence interval [CI]: [–16.0, –2.3]), followed by methylsulfonylmethane (89%), undenatured type II collagen (87%), collagen (84%), and Lanconone (82%). The SUCRA (99%) of passion fruit peel extract (MD: –41.0; 95% CI: [–66.0, –16.0]) ranked first in terms of the WOMAC function score, followed by Lanconone (95%), collagen (86%), ParActin (84%), and <em>Lactobacillus casei</em> strain Shirota (83%). The top three total rankings are passion fruit peel extract (95.0%), Lanconone (88.5%), and collagen (85.0%). However, the GRADE revealed low evidence quality.</div></div><div><h3>Conclusion</h3><div>Passion fruit peel extract was the best supplement for improving WOMAC pain and function scores in patients with osteoarthritis, followed by Lanconone and collagen. ","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":"23 4","pages":"Pages 357-369"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144162871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-01DOI: 10.1016/j.joim.2025.06.001
Wei Song Seetoh , Rachel Qin Rui Lim , Run-bing Xu , Ming-xun Sun , Peng Zhang , Mi-na Wang
Acupuncture is an ancient treatment method used in traditional Chinese medicine and has been popularized worldwide. Over the past decade, there has been an increase in the amount of acupuncture research, mostly comprised of randomized controlled trials (RCTs) that aimed to answer the question on the efficacy of acupuncture. However, poor methodology and low replicability in these acupuncture RCTs have resulted in uncertainty about the efficacy of acupuncture. In this review, current advancements and challenges in acupuncture RCTs, regarding the methodological aspects of randomization, blinding, sham acupuncture and quality of reporting, were discussed. While there have been advancements in various aspects, current acupuncture RCTs still face pressing issues such as inadequate randomization and blinding, unviable sham acupuncture controls, and poor reporting quality. Given these limitations, this review seeks to identify the methodological problems that are responsible for these problems and to suggest solutions that could help to overcome them so as to improve the quality of future studies evaluating the efficacy of acupuncture.
Please cite this article as: Seetoh WS, Lim RQR, Xu RB, Sun MX, Zhang P, Wang MN. Advancements and challenges of acupuncture randomized controlled trials. J Integr Med. 2025; 23(4): 333–343.
针灸是一种古老的中医治疗方法，在世界范围内得到推广。在过去的十年里，针灸研究的数量有所增加，主要是由随机对照试验（rct）组成，旨在回答针灸疗效的问题。然而，在这些针灸随机对照试验中，较差的方法学和较低的可重复性导致了针灸疗效的不确定性。本文综述了针刺随机对照试验在方法学方面的进展和挑战，包括随机化、盲法、假针灸和报告质量。虽然在各个方面都取得了进步，但目前的针灸随机对照试验仍然面临着随机化和盲化不足、假针灸对照不可行、报告质量差等紧迫问题。鉴于这些局限性，本综述旨在找出导致这些问题的方法学问题，并提出有助于克服这些问题的解决方案，以提高评估针灸疗效的未来研究的质量。本文署名：Seetoh WS， Lim RQR, Xu RB, Sun MX, Zhang P, Wang MN。针灸随机对照试验的进展与挑战。集成医学[J]；打印前Epub。
{"title":"Advancements and challenges of acupuncture randomized controlled trials","authors":"Wei Song Seetoh , Rachel Qin Rui Lim , Run-bing Xu , Ming-xun Sun , Peng Zhang , Mi-na Wang","doi":"10.1016/j.joim.2025.06.001","DOIUrl":"10.1016/j.joim.2025.06.001","url":null,"abstract":"<div><div>Acupuncture is an ancient treatment method used in traditional Chinese medicine and has been popularized worldwide. Over the past decade, there has been an increase in the amount of acupuncture research, mostly comprised of randomized controlled trials (RCTs) that aimed to answer the question on the efficacy of acupuncture. However, poor methodology and low replicability in these acupuncture RCTs have resulted in uncertainty about the efficacy of acupuncture. In this review, current advancements and challenges in acupuncture RCTs, regarding the methodological aspects of randomization, blinding, sham acupuncture and quality of reporting, were discussed. While there have been advancements in various aspects, current acupuncture RCTs still face pressing issues such as inadequate randomization and blinding, unviable sham acupuncture controls, and poor reporting quality. Given these limitations, this review seeks to identify the methodological problems that are responsible for these problems and to suggest solutions that could help to overcome them so as to improve the quality of future studies evaluating the efficacy of acupuncture.</div><div>Please cite this article as: Seetoh WS, Lim RQR, Xu RB, Sun MX, Zhang P, Wang MN. Advancements and challenges of acupuncture randomized controlled trials. <em>J Integr Med</em>. 2025; 23(4): 333–343.</div></div>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":"23 4","pages":"Pages 333-343"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144508930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-01DOI: 10.1016/j.joim.2025.06.005
Ya-ting Ai , Shi Zhou , Ming Wang , Tao-yun Zheng , Hui Hu , Yun-cui Wang , Yu-can Li , Xiao-tong Wang , Peng-jun Zhou
Objective
As an age-related neurodegenerative disease, the prevalence of mild cognitive impairment (MCI) increases with age. Within the framework of traditional Chinese medicine, spleen-kidney deficiency syndrome (SKDS) is recognized as the most frequent MCI subtype. Due to the covert and gradual onset of MCI, in community settings it poses a significant challenge for patients and their families to discern between typical aging and pathological changes. There exists an urgent need to devise a preliminary diagnostic tool designed for community-residing older adults with MCI attributed to SKDS (MCI-SKDS).
Methods
This investigation enrolled 312 elderly individuals diagnosed with MCI, who were randomly distributed into training and test datasets at a 3:1 ratio. Five machine learning methods, including logistic regression (LR), decision tree (DT), naive Bayes (NB), support vector machine (SVM), and gradient boosting (GB), were used to build a diagnostic prediction model for MCI-SKDS. Accuracy, sensitivity, specificity, precision, F1 score, and area under the curve were used to evaluate model performance. Furthermore, the clinical applicability of the model was evaluated through decision curve analysis (DCA).
Results
The accuracy, precision, specificity and F1 score of the DT model performed best in the training set (test set), with scores of 0.904 (0.845), 0.875 (0.795), 0.973 (0.875) and 0.973 (0.875). The sensitivity of the training set (test set) of the SVM model performed best among the five models with a score of 0.865 (0.821). The area under the curve of all five models was greater than 0.9 for the training dataset and greater than 0.8 for the test dataset. The DCA of all models showed good clinical application value. The study identified ten indicators that were significant predictors of MCI-SKDS.
Conclusion
The risk prediction index derived from machine learning for the MCI-SKDS prediction model is simple and practical; the model demonstrates good predictive value and clinical applicability, and the DT model had the best performance.
Please cite this article as: Ai YT, Zhou S, Wang M, Zheng TY, Hu H, Wang YC, Li YC, Wang XT, Zhou PJ. Development of a machine learning-based risk prediction model for mild cognitive impairment with spleen-kidney deficiency syndrome in the elderly. J Integr Med. 2025; 23(4): 390–397.
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Pub Date : 2025-07-01DOI: 10.1016/j.joim.2025.05.005
Chee Ning Wong , Yang Mooi Lim , Kai Bin Liew , Yik-Ling Chew , Ang-Lim Chua , Siew-Keah Lee
Epigallocatechin-3-gallate (EGCG), a prominent plant-based catechin predominantly derived from Camellia sinensis and widely available on the market as a health supplement, has garnered significant attention for its potential therapeutic benefits, particularly in the context of type 2 diabetes mellitus (T2DM). This review explores the multifaceted role of EGCG in addressing the “ominous octet”—the 8 core pathophysiological defects associated with T2DM. The literature search was carried out using key terms “EGCG” OR “epigallocatechin-3-gallate” OR “epigallocatechin gallate” AND “diabetes” OR “insulin resistance” OR “hyperglycemia” in the PubMed and Scopus databases. The search was constrained to articles published between January 2018 and April 2024, focusing on the document type. Full-text articles published in English and relevant to EGCG that featured a single active ingredient, included clearly explained diabetes relief mechanism, and included ominous octet aspects were included in the final review. The outcomes of the included studies were reviewed and categorized based on 8 core pathophysiological defects, collectively referred to as the ominous octet in T2DM. This review concludes that EGCG is a potent hypoglycemic agent that has beneficial effects against the ominous octet in addition to its pharmacological activities in modulating gut microbiota dysbiosis, carbohydrate digestion and metabolism, glucose transporter-mediated intestinal glucose-uptake, endothelial dysfunction, and renal damage that are significantly associated with pathogenesis of T2DM. This extensive scientific evidence suggests that EGCG may offer a novel approach to traditional antidiabetic therapies, potentially improving glycemic control and mitigating complications associated with T2DM. The inhibitory effects of EGCG on sodium-glucose transport proteins and their role in reducing renal glucose reabsorption remain unexplored, highlighting a significant research gap. Future research should also aim to broaden the scope by investigating the “egregious eleven,” which comprise a more comprehensive range of diabetic pathophysiological features. This review underscores the therapeutic promise of EGCG for managing T2DM and encourages ongoing research to fully elucidate its clinical applications.
Please cite this article as: Wong CN, Lim YM, Liew KB, Chew YL, Chua AL, Lee SK. A review on mechanistic actions of epigallocatechin-3-gallate in targeting the ominous octet of type 2 diabetes mellitus. J Integr Med. 2025; 23(4): 344–356.
表没食子儿茶素-3-没食子酸酯（EGCG）是一种重要的植物基儿茶素，主要来源于茶树，作为一种健康补充剂在市场上广泛使用，因其潜在的治疗益处而受到广泛关注，特别是在2型糖尿病（T2DM）的背景下。这篇综述探讨了EGCG在解决与T2DM相关的8个核心病理生理缺陷中的多方面作用。在PubMed和Scopus数据库中使用关键词“EGCG”或“没食子儿茶素-3-没食子酸酯”或“没食子儿茶素没食子酸酯”和“糖尿病”或“胰岛素抵抗”或“高血糖症”进行文献检索。搜索仅限于2018年1月至2024年4月之间发表的文章，重点关注文档类型。最终审评中纳入了与EGCG相关的英文全文文章，这些文章具有单一活性成分，包括明确解释糖尿病缓解机制，包括不祥的八元体方面。对纳入研究的结果进行回顾，并根据8个核心病理生理缺陷进行分类，这些缺陷统称为T2DM的不祥八组。这篇综述得出结论，EGCG是一种有效的降糖剂，除了在调节肠道微生物群失调、碳水化合物消化和代谢、葡萄糖转运体介导的肠道葡萄糖摄取、内皮功能障碍和肾脏损害方面的药理活性外，还对不祥的八糖体有有益的作用，这些与T2DM的发病机制有显著的关系。这一广泛的科学证据表明，EGCG可能为传统的降糖治疗提供一种新的方法，可能改善血糖控制并减轻T2DM相关的并发症。EGCG对钠-葡萄糖转运蛋白的抑制作用及其在减少肾葡萄糖重吸收中的作用仍未被探索，这凸显了一个重大的研究空白。未来的研究还应致力于通过调查“十一个异常”来扩大范围，这些异常包括更全面的糖尿病病理生理特征。这篇综述强调了EGCG治疗T2DM的前景，并鼓励正在进行的研究充分阐明其临床应用。黄春宁，林玉明，刘国宝，周永良，Chua AL, Lee SK.表没食子儿茶素-3-没食子酸酯治疗2型糖尿病的机制研究进展。集成医学[J]；打印前Epub。
{"title":"A review on mechanistic actions of epigallocatechin-3-gallate in targeting the ominous octet of type 2 diabetes mellitus","authors":"Chee Ning Wong , Yang Mooi Lim , Kai Bin Liew , Yik-Ling Chew , Ang-Lim Chua , Siew-Keah Lee","doi":"10.1016/j.joim.2025.05.005","DOIUrl":"10.1016/j.joim.2025.05.005","url":null,"abstract":"<div><div>Epigallocatechin-3-gallate (EGCG), a prominent plant-based catechin predominantly derived from <em>Camellia sinensis</em> and widely available on the market as a health supplement, has garnered significant attention for its potential therapeutic benefits, particularly in the context of type 2 diabetes mellitus (T2DM). This review explores the multifaceted role of EGCG in addressing the “ominous octet”—the 8 core pathophysiological defects associated with T2DM. The literature search was carried out using key terms “EGCG” OR “epigallocatechin-3-gallate” OR “epigallocatechin gallate” AND “diabetes” OR “insulin resistance” OR “hyperglycemia” in the PubMed and Scopus databases. The search was constrained to articles published between January 2018 and April 2024, focusing on the document type. Full-text articles published in English and relevant to EGCG that featured a single active ingredient, included clearly explained diabetes relief mechanism, and included ominous octet aspects were included in the final review. The outcomes of the included studies were reviewed and categorized based on 8 core pathophysiological defects, collectively referred to as the ominous octet in T2DM. This review concludes that EGCG is a potent hypoglycemic agent that has beneficial effects against the ominous octet in addition to its pharmacological activities in modulating gut microbiota dysbiosis, carbohydrate digestion and metabolism, glucose transporter-mediated intestinal glucose-uptake, endothelial dysfunction, and renal damage that are significantly associated with pathogenesis of T2DM. This extensive scientific evidence suggests that EGCG may offer a novel approach to traditional antidiabetic therapies, potentially improving glycemic control and mitigating complications associated with T2DM. The inhibitory effects of EGCG on sodium-glucose transport proteins and their role in reducing renal glucose reabsorption remain unexplored, highlighting a significant research gap. Future research should also aim to broaden the scope by investigating the “egregious eleven,” which comprise a more comprehensive range of diabetic pathophysiological features. This review underscores the therapeutic promise of EGCG for managing T2DM and encourages ongoing research to fully elucidate its clinical applications.</div><div>Please cite this article as: Wong CN, Lim YM, Liew KB, Chew YL, Chua AL, Lee SK. A review on mechanistic actions of epigallocatechin-3-gallate in targeting the ominous octet of type 2 diabetes mellitus. <em>J Integr Med</em>. 2025; 23(4): 344–356.</div></div>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":"23 4","pages":"Pages 344-356"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-01DOI: 10.1016/j.joim.2025.06.004
Ya-jie Cai , Jian-hang Lan , Shuo Li , Yue-ning Feng , Fang-hong Li , Meng-yu Guo , Run-ping Liu
Objective
Ulcerative colitis is closely associated with intestinal stem cell (ISC) loss and impaired intestinal mucus barrier. Sinisan (SNS), a compound Chinese herbal medicine, has a long history in the treatment of intestinal dysfunction, yet whether SNS can relieve acute experimental colitis by modulating ISC proliferation and secretory cell differentiation has not been studied. Our study tested the effect of SNS against acute colitis and focused on the mechanisms involving intestinal barrier recovery.
Methods
Network pharmacology analysis and blood entry component analysis of SNS were used to explore the underlying mechanism by which SNS affects the acute dextran sulfate sodium (DSS)-induced murine colitis model. RNA-sequencing was used to demonstrate the mechanism. Further, reverse transcription-quantitative polymerase chain reaction, immunofluorescence staining, and alcian blue and periodic acid-Schiff staining were performed in vivo and in the colonic organoids to investigate the cell lineage differentiation-related mechanism of SNS. Furthermore, potential active ingredients from SNS were predicted by network pharmacology analysis.
Results
SNS dramatically suppressed DSS-induced acute colonic inflammation in mice. RNA-sequencing analysis revealed downregulation of inflammation and apoptosis-related genes, and upregulation of lipid metabolism and proliferation-related genes, such as Irf7, Pparα, Clspn and Hspa5. Additionally, ISC renewal and intestinal secretory cell lineage commitment were significantly promoted by SNS both in vivo and in vitro in colonic organoids, leading to enhanced mucin expression. Furthermore, potential active ingredients from SNS that mediated inflammation, lipid metabolism, proliferation, apoptosis, stem cells and secretory cells were predicted using a network pharmacology approach.
Conclusion
Our study shed light on the underlying mechanism of SNS in attenuating acute colitis from the perspective of ISC renewal and secretory lineage cell differentiation, suggesting a of novel therapeutic strategy against colitis.
Please cite this article as: Cai YJ, Lan JH, Li S, Feng YN, Li FH, Guo MY, et al. Sinisan, a compound Chinese herbal medicine, alleviates acute colitis by facilitating colonic secretory cell lineage commitment and mucin production. J Integr Med. 2025; 23(4): 429–444.
{"title":"Sinisan, a compound Chinese herbal medicine, alleviates acute colitis by facilitating colonic secretory cell lineage commitment and mucin production","authors":"Ya-jie Cai , Jian-hang Lan , Shuo Li , Yue-ning Feng , Fang-hong Li , Meng-yu Guo , Run-ping Liu","doi":"10.1016/j.joim.2025.06.004","DOIUrl":"10.1016/j.joim.2025.06.004","url":null,"abstract":"<div><h3>Objective</h3><div>Ulcerative colitis is closely associated with intestinal stem cell (ISC) loss and impaired intestinal mucus barrier. Sinisan (SNS), a compound Chinese herbal medicine, has a long history in the treatment of intestinal dysfunction, yet whether SNS can relieve acute experimental colitis by modulating ISC proliferation and secretory cell differentiation has not been studied. Our study tested the effect of SNS against acute colitis and focused on the mechanisms involving intestinal barrier recovery.</div></div><div><h3>Methods</h3><div>Network pharmacology analysis and blood entry component analysis of SNS were used to explore the underlying mechanism by which SNS affects the acute dextran sulfate sodium (DSS)-induced murine colitis model. RNA-sequencing was used to demonstrate the mechanism. Further, reverse transcription-quantitative polymerase chain reaction, immunofluorescence staining, and alcian blue and periodic acid-Schiff staining were performed in vivo and in the colonic organoids to investigate the cell lineage differentiation-related mechanism of SNS. Furthermore, potential active ingredients from SNS were predicted by network pharmacology analysis.</div></div><div><h3>Results</h3><div>SNS dramatically suppressed DSS-induced acute colonic inflammation in mice. RNA-sequencing analysis revealed downregulation of inflammation and apoptosis-related genes, and upregulation of lipid metabolism and proliferation-related genes, such as <em>Irf7</em>, <em>Pparα</em>, <em>Clspn</em> and <em>Hspa5</em>. Additionally, ISC renewal and intestinal secretory cell lineage commitment were significantly promoted by SNS both in vivo and in vitro in colonic organoids, leading to enhanced mucin expression. Furthermore, potential active ingredients from SNS that mediated inflammation, lipid metabolism, proliferation, apoptosis, stem cells and secretory cells were predicted using a network pharmacology approach.</div></div><div><h3>Conclusion</h3><div>Our study shed light on the underlying mechanism of SNS in attenuating acute colitis from the perspective of ISC renewal and secretory lineage cell differentiation, suggesting a of novel therapeutic strategy against colitis.</div><div>Please cite this article as: Cai YJ, Lan JH, Li S, Feng YN, Li FH, Guo MY, et al. Sinisan, a compound Chinese herbal medicine, alleviates acute colitis by facilitating colonic secretory cell lineage commitment and mucin production. <em>J Integr Med</em>. 2025; 23(4): 429–444.</div></div>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":"23 4","pages":"Pages 429-444"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-01DOI: 10.1016/j.joim.2025.06.002
Zhi-han Li , Wen-min Yang , Qi Huang , Guang-xia Shi , Cun-zhi Liu , Yu-qin Zhang
Objective
The occurrence and development of atrial fibrillation (AF) are influenced by the autonomic nervous system and inflammation. Acupuncture is an effective treatment for AF. This study explored the protective effects of acupuncture in a rat model of paroxysmal AF and investigated its mechanisms.
Methods
Male Sprague-Dawley rats (n = 130) were randomly divided into blank control (Con), sham operation (Sham), AF, and acupuncture treatment (Acu) groups. A paroxysmal AF model was established by rapid atrial pacing through the jugular vein. Rats in the Acu group were immobilized to receive acupuncture treatment at Neiguan acupoint (PC6) for 20 min daily for seven days. The other groups were immobilized for the same duration over the treatment period but did not receive acupuncture. The AF induction rate, AF duration, cardiac electrophysiological parameters, and heart rate variability were evaluated by monitoring surface electrocardiogram and vagus nerve discharge signals. After the intervention, the rats were euthanized, and atrial morphology was assessed using haematoxylin and eosin staining. The expression of macrophage F4/80 antigen (F4/80) and cluster of differentiation (CD) 86 in atrial myocardial tissue was detected using immunohistochemistry, immunofluorescence and flow cytometry. The expression levels or contents of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), α7 nicotinic acetylcholine receptor (α7nAChR), phosphorylated Janus kinase 2 (p-JAK2), and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in atrial myocardial tissue were detected using Western blotting, reverse transcription-quantitative polymerase chain reaction, or enzyme-linked immunosorbent assay. The role of α7nAChR in acupuncture treatment was verified by intraperitoneal injection of the α7nAChR antagonist methyllycaconitine (MLA).
Results
Compared with the AF group, acupuncture significantly reduced AF duration and induction rate, improved cardiac electrophysiology by enhancing vagus nerve activity and regulating autonomic balance. It also decreased the pro-inflammatory M1 macrophage proportion, alleviating myocardial injury and infiltration. MLA weakened acupuncture’s electrophysiological improvement and anti-inflammatory effect. Results suggest that acupuncture triggers the α7nAChR-JAK2/STAT3 pathway and exerts cardioprotection via neuroimmune regulation.
Conclusion
Acupuncture significantly reduced the AF induction rate, shortened AF duration, improved cardiac electrophysiological parameters, enhanced vagus nerve activity, and decreased the expression of pro-inflammatory M1 macrophages and inflammatory factors in rats with paroxysmal AF. Its positive effects are related to the activation of the α7nAChR-mediated JAK2/STAT3 signalling pathway, indicating that the interaction between cardiac vagus nerve and macrophages
{"title":"Acupuncture activates vagus nerve-macrophage axis and improves cardiac electrophysiology and inflammatory response in rats with atrial fibrillation via α7nAChR-JAK2/STAT3 pathway","authors":"Zhi-han Li , Wen-min Yang , Qi Huang , Guang-xia Shi , Cun-zhi Liu , Yu-qin Zhang","doi":"10.1016/j.joim.2025.06.002","DOIUrl":"10.1016/j.joim.2025.06.002","url":null,"abstract":"<div><h3>Objective</h3><div>The occurrence and development of atrial fibrillation (AF) are influenced by the autonomic nervous system and inflammation. Acupuncture is an effective treatment for AF. This study explored the protective effects of acupuncture in a rat model of paroxysmal AF and investigated its mechanisms.</div></div><div><h3>Methods</h3><div>Male Sprague-Dawley rats (<em>n</em> = 130) were randomly divided into blank control (Con), sham operation (Sham), AF, and acupuncture treatment (Acu) groups. A paroxysmal AF model was established by rapid atrial pacing through the jugular vein. Rats in the Acu group were immobilized to receive acupuncture treatment at Neiguan acupoint (PC6) for 20 min daily for seven days. The other groups were immobilized for the same duration over the treatment period but did not receive acupuncture. The AF induction rate, AF duration, cardiac electrophysiological parameters, and heart rate variability were evaluated by monitoring surface electrocardiogram and vagus nerve discharge signals. After the intervention, the rats were euthanized, and atrial morphology was assessed using haematoxylin and eosin staining. The expression of macrophage F4/80 antigen (F4/80) and cluster of differentiation (CD) 86 in atrial myocardial tissue was detected using immunohistochemistry, immunofluorescence and flow cytometry. The expression levels or contents of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), α7 nicotinic acetylcholine receptor (α7nAChR), phosphorylated Janus kinase 2 (p-JAK2), and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in atrial myocardial tissue were detected using Western blotting, reverse transcription-quantitative polymerase chain reaction, or enzyme-linked immunosorbent assay. The role of α7nAChR in acupuncture treatment was verified by intraperitoneal injection of the α7nAChR antagonist methyllycaconitine (MLA).</div></div><div><h3>Results</h3><div>Compared with the AF group, acupuncture significantly reduced AF duration and induction rate, improved cardiac electrophysiology by enhancing vagus nerve activity and regulating autonomic balance. It also decreased the pro-inflammatory M1 macrophage proportion, alleviating myocardial injury and infiltration. MLA weakened acupuncture’s electrophysiological improvement and anti-inflammatory effect. Results suggest that acupuncture triggers the α7nAChR-JAK2/STAT3 pathway and exerts cardioprotection via neuroimmune regulation.</div></div><div><h3>Conclusion</h3><div>Acupuncture significantly reduced the AF induction rate, shortened AF duration, improved cardiac electrophysiological parameters, enhanced vagus nerve activity, and decreased the expression of pro-inflammatory M1 macrophages and inflammatory factors in rats with paroxysmal AF. Its positive effects are related to the activation of the α7nAChR-mediated JAK2/STAT3 signalling pathway, indicating that the interaction between cardiac vagus nerve and macrophages","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":"23 4","pages":"Pages 398-414"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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