Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations.

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.

Background

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.

Objective

This study aims to provide a comprehensive evaluation of the available evidence concerning the efficacy of various dietary supplements in osteoarthritis treatment.

Search strategy

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.

Inclusion criteria

(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).

Data extraction and analysis

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.

Results

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 Lactobacillus casei 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.

Conclusion

Passion fruit peel extract was the best supplement for improving WOMAC pain and function scores in patients with osteoarthritis, followed by Lanconone and collagen. However, further large-scale, well designed RCTs are required to substantiate these promising findings.

Atopic dermatitis (AD) is the most common chronic inflammatory skin condition. It has significant socioeconomic consequences and complex pathophysiology, necessitating updated management guidelines that consider the age, sex and geographic location of patients. Despite the widespread use of Western medicine (WM), including topical corticosteroids, as the primary treatment for AD, the possible negative effects of WM therapies are inescapable. Although there is still a lack of strong evidence, the integration of traditional Chinese medicine (TCM) with WM may yield a more favorable therapeutic response for AD than WM alone, due to the synergistic effects involved. Balancing the application of diagnostic and therapeutic approaches from TCM and WM is crucial for the management of AD, enhancing treatment efficacy for patients, and averting disease recurrence. In 2025, a new clinical guideline for the diagnosis and treatment of AD was released; it emphasized the integration of TCM with WM. This guideline is crucial as it consolidates global expertise and data to provide a standardized framework for the practical integration of techniques to bridge divides among clinical disciplines. As more substantial data emerge, the development and enhancement of integrative medicine for AD management should be prioritized globally, particularly in Asian regions. Please cite this article as: Chen M, Liao WQ. Atopic dermatitis management in the era of integrative medicine. J Integr Med. 2026; 24(2):137-139.

Background

Acupuncture therapy provides a complementary and alternative approach to treating major depressive disorder (MDD), but its efficacy and safety have still not been comprehensively assessed. Recently published systematic reviews remain confusing and inconclusive.

Objective

This systematic review evaluated the efficacy and safety of acupuncture therapy alone or combined with antidepressants for adult patients with mild and moderate MDD.

Search strategy

Chinese Biomedical Literature Database, China National Knowledge Infrastructure Database, Wanfang Database, Chinese Science and Technology Journal Database, PubMed, Embase, and Cochrane Library were searched from their inceptions to March 2025.

Inclusion criteria

Randomized controlled trials that compared acupuncture therapy with antidepressants, or acupuncture therapy plus antidepressants with acupuncture therapy or antidepressants for adult patients with mild and moderate MDD were included.

Data extraction and analysis

Five reviewers independently extracted data from original literature using a standardized form, and the data were verified by two reviewers to ensure accuracy. Statistical meta-analyses, publication bias analyses, and subgroup analyses were performed by using Review Manager 5.3 software. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the certainty of the evidence.

Results

A total of 60 eligible studies including 4675 participants were included. Low-certainty evidence showed that compared with antidepressants, acupuncture therapy (standardized mean difference [SMD] = –0.57; 95% confidence interval [CI] = [–0.87, –0.27]; I² = 86%; P = 0.006) or acupuncture therapy plus antidepressants (SMD = –1.00; 95% CI = [–1.18, –0.81]; I² = 77%; P < 0.00001) may reduce the severity of depression at the end of treatment. Low-certainty evidence indicated that compared with acupuncture therapy alone, acupuncture therapy plus antidepressants slightly reduced the severity of depression at the end of treatment (SMD = –0.38; 95% CI = [–0.61, –0.14]; I² = 18%; P = 0.002). Similar results were also found for acupuncture’s relief of insomnia. The reported adverse effects of acupuncture therapy were mild and transient. For most of the subgroup analyses, acupuncture type, scale type, and the course of treatment did not show a significant relative effect.

Conclusion

Acupuncture therapy may provide antidepressant effects and relieve insomnia with mild adverse effects for adult patients with mild and moderate MDD. But the certainty of evidence was very low. More high-quality, well designed, large-scale studies with long-term follow-up are needed in the future.

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.

This study summarizes and discusses the characteristics and essence of meridians and acupoints from the perspectives of physics, chemistry and biology. An extensive body of literature from PubMed and the China National Knowledge Infrastructure was reviewed and categorized into three distinct groups: physical characteristics-related research (75 articles), which examined electrical, thermal, optical, acoustic and magnetic properties, and isotope migration; chemical characteristics-related literature (44 articles), focusing on chemical ions, oxygen partial pressure, nitric oxide and substance P; and biological essence-related research (52 articles), which primarily explored microcirculation, extracellular fluid channels, mast cells, telocytes, connexins, hilum of muscle and bone, and sensory nerve fibers. Current research emphasizes the electrical and thermal properties of the meridians and acupoints, whereas investigations into the essence of meridians are increasingly shifting from macroscopic to microscopic structures. It is essential to fully harness the advantages of interdisciplinary integration, which could significantly advance our understanding and applications in the realm of acupuncture and traditional medicine.

This perspective review explores the transformative potential of personalized herbal medicine, examines the integration of ancient herbal knowledge with modern personalized medicine, delves into the principles of personalized medicine particularly in the context of herbal treatments, and investigates the principles of personalized medicine and elucidates how they are being applied to herbal medicine. It emphasizes the individualized nature of this approach and how it is facilitated through genetic analysis and health profiling. This review also highlights key advancements in herbal medicine, such as deoxyribonucleic acid (DNA) analysis and bioinformatics, and their role in the development of precise and personalized herbal remedies. The outcomes of personalized herbal medicine reveal how genetic variations are being considered to tailor treatments, create target-specific therapies, and customize dosage regimens. Furthermore, this review illustrates the evolution of herbal medicine with technological advancements, particularly DNA analysis and bioinformatics, to enhance precision and personalization. The challenge associated with implementing personalized herbal medicine more broadly includes issues of accessibility, regulation, education and ethics. It underscores the transformative potential of personalized herbal medicine. It calls for continued exploration, research and collaboration in this burgeoning field. This uncharted territory invites researchers, practitioners and stakeholders to embark on a journey towards an era of healthcare characterized by tailored, effective and patient-centric approaches

Objective

Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF.

Methods

The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations.

Results

Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells.

Conclusion

AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.

To improve the consistency of outcome documentation and address the potential for outcome reporting bias in clinical trials involving integrative Chinese and Western medicine (ICWM) for ulcerative colitis (UC), we aim to develop a customized core outcome set (COS) that incorporates input from various stakeholders. The study design of this COS has been informed by the Core Outcome Measures in Effectiveness Trials Initiative Handbook, with adherence to the guidelines from the Core Outcome Set-STAndards for Reporting statement and Core Outcome Set-STAndardised Protocol Items recommendations. Five groups of stakeholders will be invited to participate in the development of COS for clinical trials with ICWM for UC, including healthcare professionals, patients, COS developers, COS users, and methodologists. The process will involve five stages: (1) conducting a systematic review of outcomes reported in clinical trials and protocols to develop a list of potential outcome domains; (2) conducting semi-structured interviews to obtain important outcomes; (3) choosing the most important outcomes by conducting three-round Delphi surveys; (4) achieving a consensus in a face-to-face meeting to discuss the final COS; and (5) publication, dissemination and implementation of COS. Consequently, this specialized COS will be applicable to clinical trials involving both traditional Chinese medicine (TCM) and ICWM interventions. Please cite this article as: Zhang X, Zhang L, Wang J, Lau CT, Wang N, Zhang X, Wang P, Li J, Han F, Bian Z. A protocol for developing, disseminating and implementing a core outcome set for clinical trials of integrative Chinese and Western medicine for ulcerative colitis. J Integr Med. 2025; 23(6):654-659.

Objective

Angiogenesis is a critical target for hepatocellular carcinoma (HCC) treatment. The previous studies indicated that Jiedu Fang (JDF) could inhibit hypoxia-induced angiogenesis through interleukin-8 (IL-8). Therefore, the present study further explores the mechanisms behind JDF’s inhibition of HCC angiogenesis.

Methods

Angiogenesis was assessed with the capillary-like tube formation assay in vitro and the matrigel plug angiogenesis assay in vivo. A liver cancer-related gene set and genes associated with angiogenesis and the hypoxic microenvironment were analyzed using a bioinformatics platform. Real-time reverse transcription-polymerase chain reaction and Western blotting assays were used to assess the targeted mRNA and protein levels, respectively. The Transwell assay was used to assess the migration and invasion potential of EA.hy 926 cells. The orthotopic tumor xenograft model was established, and immunohistochemistry and immunofluorescence assays were used to detect CD31 and angiopoietin 2 expression, while an enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor and IL-8 protein levels.

Results

In vitro and in vivo assays showed that IL-8 promoted angiogenesis, and JDF could antagonize this effect. Bioinformatics analysis indicated that aurora kinase A (Aurora A) was an important candidate, which can promote IL-8 expression through activation of signal transducer and activator of transcription 3 (STAT3). The overexpression of Aurora A increased IL-8 secretion and promoted HCC migration, invasion, and angiogenesis, which was partly inhibited by JDF. Such effects were validated by in vivo assays. Further validation using the STAT3 inhibitor S3I-201 demonstrated that STAT3 was regulated by Aurora A.

Conclusion

JDF exhibits efficacy in reducing hypoxia-induced angiogenesis in HCC through a mechanism involving the Aurora A/STAT3/IL-8 signaling pathway. Therefore, JDF holds promise as a potential therapeutic approach for targeting HCC angiogenesis.

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.

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 may be a potential target for acupuncture in the prevention and treatment of AF.

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.

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.

Objective:This cross-sectional study assessed the methodological quality of systematic reviews (SRs) of Chinese herbal medicine (CHM) published in Chinese between Jan 2021 and Sep 2022.

Methods:Chinese language CHM SRs were identified through literature searches across 3 international and 4 Chinese databases. Methodological quality was appraised using A MeaSurement Tool to Assess systematic Reviews 2. Logistic regressions were used to explore associations between bibliographical characteristics and quality.

Results:Analyses of methodological quality found that among the 213 sampled SRs, 69.5% were of critically low quality, 30.5% were of low quality, and none achieved high or moderate quality. Common shortcomings included the failure to identify the studies excluded from the analysis, failure to disclose funding sources, and limited evaluation of the potential impact of bias on conclusions. Logistic regressions revealed that SRs led by corresponding authors affiliated with universities or academic institutions tended to be of lower quality than SRs led by authors affiliated with hospitals or clinical facilities.

Conclusion:Recent Chinese language CHM SRs exhibited limited methodological quality, making them unlikely to support the development of clinical practice guidelines. Urgent initiatives are needed to enhance training for researchers, peer-reviewers and editors involved in the preparation and publication of SRs. Adoption of Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines in Chinese language journals is crucial to improve the relevance of SRs for Chinese medicine development. Addressing deficiencies in methodology and reporting is essential for promoting evidence-based practices and informed clinical decisions in Chinese medicine. Please cite this article as: Jiang Y, Zhong CC, Wang BH, Xu SS, Ho FF, Kwong MH, Ho L, Zhou JHS, Lam KC, Liu JP, Zhang BT, Chung VCH. Methodological quality of systematic reviews on orally administered Chinese herbal medicine published in Chinese between 2021 and 2022: A cross-sectional study. J Integr Med. 2025; 23(5):492-501.

Acupuncture therapy has demonstrated therapeutic effects on various systemic diseases through the use of specific acupoints along meridians. However, due to the multi-target effect of acupuncture and the complexity of meridian pathways, the underlying mechanisms of acupuncture have not been well understood. Tissue clearing and three-dimensional (3D) imaging is an emerging medical technology that provides high-resolution 3D molecular information while preserving the structural integrity of tissues. In relevant research articles, tissue-clearing and 3D imaging techniques stood out for their ability to visualize the structural characteristics of meridians and acupoints of intact tissues, in order to reveal their intricate connections by means of topological principles. Specifically, this technology has managed to show that acupuncture points like Guilai (ST29) and Sanyinjiao (SP6), which are commonly used in traditional Chinese medicine for treating gynecological disorders, promote angiogenesis in the ovaries and thus improve follicle numbers in polycystic ovary syndrome-like ovaries. This article summarizes recent progress on tissue-clearing and 3D imaging technologies and anticipates the prospects of utilizing this technology to further explore the effects of acupuncture.

Background

Acupuncture is recognized as an alternative therapy for rheumatoid arthritis (RA) pain, but its efficacy evaluations are often confounded by variability in sham acupuncture techniques. The accurate selection of sham acupuncture controls, which are administered at either therapeutic acupuncture points or non-acupuncture points, is crucial for the validity of assessment outcomes.

Objective

To assess the efficacy of acupuncture in treating RA pain and identify the most effective acupuncture methods.

Search strategy

Databases including MEDLINE, Embase, PubMed, Cochrane Library, Scopus, Web of Science, China National Knowledge Infrastructure Database, Chinese Science and Technology Journal Database, and Wanfang Database were searched from inception to October 11, 2024. Keywords included “rheumatoid arthritis,” “acupuncture,” “electroacupuncture,” and “pain.”

Inclusion criteria

Randomized controlled trials (RCTs) in adults with RA that assessed pain using a visual analog scale and joint swelling by swollen joint count. Eligible trials compared electroacupuncture, conventional acupuncture, or sham acupuncture, against standard pain medication.

Data extraction and analysis

Two reviewers independently extracted data on study design, participant characteristics, interventions and outcomes. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool, and evidence certainty was assessed via the confidence in network meta-analysis framework. A frequentist network meta-analysis with random-effect models was conducted, and standardized mean difference (SMD) and 95% confidence interval (CI) were reported.

Results

Ten RCTs involving 704 participants were analyzed. Electroacupuncture (SMD: –1.42; 95% CI: [–1.87, –0.98]) and conventional acupuncture (SMD: –1.11; 95% CI: [–1.49, –0.73]) outperformed conventional therapy and non-acupoint sham needling. Surface under cumulative ranking curve showed that electroacupuncture was most effective for pain reduction (97.7%), followed by conventional acupuncture (75.1%), non-acupoint sham (29.1%), same-acupoint sham (28.6%), and conventional therapy (19.5%).

Conclusion

Electroacupuncture demonstrated the highest efficacy for RA pain relief. Same-acupoint sham acupuncture may underestimate acupuncture’s true effect and is not recommended as a placebo control. Non-acupoint sham acupuncture is a more valid control for future trials.

Objective

Psoriasis, a common chronic inflammatory skin condition with genetic underpinnings, is traditionally managed with cupping therapy. Although used historically, the precise mechanical effects and therapeutic mechanisms of cupping in psoriasis remain largely unexamined. This study aimed to evaluate cupping therapy’s efficacy for psoriasis and investigate its role in modulating inflammatory responses and cellular metabolism.

Methods

Psoriasis was induced in mice using topical imiquimod (IMQ). The effects of cupping on psoriatic lesions were assessed using the Psoriasis Area and Severity Index score, histology, immunohistochemistry, and immunofluorescence staining. polymerase chain reaction sequencing (RNA-seq) and Western blotting were conducted to examine changes in mRNA expression and the AMP-activated protein kinase (AMPK) signaling pathway.

Results

Cupping therapy significantly reduced inflammation, epidermal thickness, and inflammatory cell infiltration in mice with IMQ-induced psoriasis. Immunohistochemistry and immunofluorescence showed lower expression of inflammatory markers and a shift in T-cell populations. RNA-seq and Western blotting indicated that cupping upregulated Piezo1 and activated the AMPK pathway, improving energy metabolism in psoriatic skin.

Conclusion

Cupping therapy reduces epidermal hyperproliferation and inflammation in psoriasis, rebalancing the local immune microenvironment. Mechanistically, cupping promotes calcium influx via Piezo1, activates AMPK signaling, and supports metabolic homeostasis, suggesting therapeutic potential for psoriasis.

Background

The use of complementary and alternative medicine (CAM) is common among individuals with underlying chronic illnesses. 

Objective

This systematic review and meta-analysis investigated the global prevalence and patterns of CAM use among individuals with chronic kidney disease (CKD).

Search strategy

PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature Plus were searched from inception until 26th February, 2024.

Inclusion criteria

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.

Data extraction and analysis

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.

Results

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%), I² = 99.45%. 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 include 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.

Conclusion

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.

Objective

This study investigated the antidepression mechanisms of Xiaoyaosan (XYS), a classic Chinese prescription, from the perspective of energy metabolism in the brain and intestinal tissues.

Methods

Chronic unpredictable mild stress model—a classic depression rat model—was established. Effects of XYS on behaviors and gastrointestinal motility of depressed rats were investigated. Effects of XYS on energetic charge (EC), adenosine triphosphate-related enzymes, and key enzymes of energy metabolism in both hippocampus and jejunum tissues of depressed rats were investigated using high-performance liquid chromatography, biochemical analysis, and real-time quantitative polymerase chain reaction, respectively. Spearman correlation analysis was conducted to construct a correlation network of “behavior-brain energy metabolism-intestinal energy metabolism” of depression.

Results

XYS significantly reduced the abnormal behaviors observed in depressed rats and increased the EC and the activity of Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase in hippocampus and jejunum tissues of depressed rats. XYS restored the key energetic pathways that had been interrupted by depression, including glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, XYS exhibited antidepressive effects in terms of regulating energy metabolism in tissues of the brain and intestine.

Conclusion

XYS significantly corrected the disturbances in EC and energy metabolism-related enzymes of both brain and intestinal tissues, alleviating both core and concomitant symptoms of depression. The current findings underscore the role of energy metabolism in the antidepressive activity of XYS, providing a fresh perspective on depression, and novel research strategies for revealing the mechanism of actions of traditional Chinese medicines on multi-site and multi-symptom diseases.

Objective

Glucocorticoid-induced osteoporosis (GIOP) is a common complication of prolonged glucocorticoid therapy. Chlorogenic acid (CGA), a polyphenol with antioxidant properties that is extracted from traditional Chinese medicines such as Eucommiae Cortex, has potential anti-osteoporotic activity. This study aimed to investigate the possible effects of CGA on GIOP in mice and murine long bone osteocyte Y4 (MLO-Y4) cells and explore the underlying molecular mechanisms.

Methods

The protective effects of CGA were initially evaluated in the GIOP mouse model induced by dexamethasone (Dex). The micro-computed tomography, hematoxylin-eosin staining, silver nitrate staining, and serum detection were used to assess the efficacy of CGA for improving bone formation in vivo. Then, network pharmacology analysis was used to predict the potential targets and molecular mechanisms underlying the therapeutic efficacy of CGA against GIOP. After that, 2',7'-dichlorofluorescein diacetate staining, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, and Western blotting were used to verify the mechanisms of CGA against GIOP in vitro.

Results

Animal experiments showed that CGA treatment effectively attenuated Dex-induced decreases in bone mass and strength and improved disrupted osteocyte morphology in mice. The protein-protein interaction analysis highlighted erb-b2 receptor tyrosine kinase (ERBB2), which is also known as human epidermal growth factor receptor 2 (HER2), caspase-3, kinase insert domain receptor, matrix metallopeptidase 9, matrix metallopeptidase 2, proto-oncogene tyrosine-protein kinase Src, and epidermal growth factor receptor as core targets. The Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched pathways (P < 0.05), including the ERBB, phosphoinositide 3 kinase-AKT serine/threonine kinase 1 (AKT), and mechanistic target of rapamycin kinase (mTOR) pathways. Cellular experiments verified that CGA enhanced bone formation and promoted autophagy while inhibiting apoptosis in MLO-Y4 cells exposed to Dex, which was associated with the upregulated expression of HER2 and activation of the HER2/AKT/mTOR signaling pathway.

Conclusion

CGA exerted anti-osteoporotic effects against GIOP, partially through targeting osteocytes and modulating the HER2/AKT/mTOR signaling pathway. Please cite this article as: Xie AN, Zhang SZY, Zhang Y, Cao JL, Wang CL, Wang LB, Wu HJ, Zhang J, Dai WW. Chlorogenic acid mitigates glucocorticoid-induced osteoporosis via modulation of HER2/AKT/mTOR signaling pathway. J Integr Med. 2025; 23(6):670-682.

Background

The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment.

Objective

This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects.

Search strategy

PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022.

Inclusion criteria

RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment.

Data extraction and analysis

The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES.

Results

This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs.

Conclusion

The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.

Salvia miltiorrhiza (Danshen) is a traditional Chinese herb that is commonly known for its cardiovascular and hepatoprotective benefits. Recent studies have confirmed that Danshen and its bioactive components can influence gut microbial homeostasis, thereby affecting Helicobacter pylori (HP) colonization in the human stomach. HP is a bacterial pathogen associated with various gastrointestinal diseases. Current HP treatments mainly involve antibiotics and proton pump inhibitors. However, their efficacy is strongly compromised by the rapid emergence of antibiotic resistance in HP and genetic heterogeneity among patients. The interaction between Danshen and gut microbial status provides a novel perspective for HP treatment. Understanding the medical properties of Danshen in altering gut microbiota and eliminating HP, as well as the underlying mechanisms, is important for improving human gastrointestinal healthcare. This review investigates the interaction between Danshen and gut microbiota and its impact on HP infection using databases including Web of Science, PubMed, and Google Scholar. We explored the unconventional intersection between Danshen, gut microbiota, and HP infection, shedding light on their intricate interplay and potential therapeutic implications. A comprehensive understanding of this interaction provides valuable insights into developing novel therapeutic strategies that target the gut microbiota to mitigate HP-associated gastrointestinal disorders.

Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments.

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.

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.

Type 2 diabetes mellitus (T2DM) is a highly prevalent chronic metabolic disease with an increasing incidence worldwide, that poses a significant risk to public health. In many current clinical practices for diabetes management, conventional Western treatments, including oral or injectable hypoglycemic agents, have serious side effects. Given that traditional Chinese medicine (TCM) is characterized by a multi-component, multi-target and multi-pathway approach, its combination with Western medicine could enhance efficacy and reduce adverse effects. Consequently, the use of TCM as a potential auxiliary or alternative treatment for the prevention and/or management of T2DM has emerged as a research hotspot. This article reviews existing reports on TCM in the treatment of T2DM and provides a detailed discussion of its applications. By integrating relevant clinical evidence, this review summarizes the clinical data on 23 TCM formulas and Chinese patent medicines, comprehensively describing their efficacy and potential pharmacological mechanisms in the treatment of T2DM. This includes an exploration of the impacts of TCM-based therapeutic interventions on T2DM-related microRNAs and their target genes. We hope this review not only offers new insights for future research directions but also enhances the understanding of the scientific value of TCM.

Objective: Cerebral ischemic stroke (CIS) induces neuronal damage and activates neuronal autophagy through diverse mechanisms. Autophagy exerts adverse effects in acute neurological disorders, leading to neuronal apoptosis and death. The dried tuberous root of Aconitum coreanum (H.Le?v l.) Rapaics is a traditional herbal medicine that has been used to treat stroke. This study explores the neuroprotective effects of A. coreanum through its role in autophagy and the mechanisms that underly this activity.

Methods: The middle cerebral artery occlusion/reperfusion technique was used to establish a CIS rat model. The neuroprotective effects of A. coreanum were explored using a suite of techniques: behavioral injury was assessed with the Longa method; infarct size was measured using 2,3,5-triphenyltetrazolium chloride; neuronal morphology was observed using hematoxylin–eosin and Nissl staining; neuronal apoptosis was observed with terminal-deoxynucleotidyl transferase dUTP nick-end labeling staining. Then, the mechanisms behind the neuroprotective effects were explored: the oxidative stress index was detected using enzyme-linked immunosorbent assay; the ultrastructure of rat neurons was observed using transmission electron microscopy; the protein expression was detected with Western blotting and immunofluorescence analyses; the mRNA expression was measured by quantitative reverse transcription-polymerase chain reaction analysis.

Results: A. coreanum significantly reduced the behavioral score and infarct size of CIS rats, increased the number of neurons in the cerebral cortex and hippocampus, improved the morphology and structure of neurons, and suppressed neuronal apoptosis. In addition, A. coreanum downregulated levels of malondialdehyde and myeloperoxidase and upregulated those of superoxide dismutase and glutathione. It inhibited the generation of autophagosomes and modulated the indicators of autophagy, including decreasing the ratio of microtubule-associated protein 1 light chain 3-II (LC3-II)/LC3-I, and increasing the expression of sequestosome 1. A. coreanum also upregulated the expression of phosphorylated mammalian target of rapamycin (mTOR) and phosphorylated unc-51-like kinase 1 (ULK1) and downregulated that of phosphorylated adenosine monophosphate-activated protein kinase (AMPK).

Conclusion: A. coreanum exerts neuroprotective effects in CIS by inhibiting autophagy through regulating the AMPK/mTOR/ULK1 signaling pathway. This finding provides a novel perspective on the treatment of CIS with A. coreanum.

Objective:Baicalein has been reported to have wide therapeutic effects that act through its anti-inflammatory activity. This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy (SIC).

Methods:A thorough screening of a small library of natural products, comprising 100 diverse compounds, was conducted to identify the most effective drug against lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes. The core target proteins and their associated signaling pathways involved in baicalein's efficacy against LPS-induced myocardial injury were predicted by network pharmacology.

Results:Baicalein was identified as the most potent protective agent in LPS-exposed H9C2 cardiomyocytes. It exhibited a dose-dependent inhibitory effect on cell injury and inflammation. In the LPS-induced septic mouse model, baicalein demonstrated a significant capacity to mitigate LPS-triggered myocardial deficits, inflammatory responses, and ferroptosis. Network pharmacological analysis and experimental confirmation suggested that hypoxia-inducible factor 1 subunit α (HIF1-α) is likely to be the crucial factor in mediating the impact of baicalein against LPS-induced myocardial ferroptosis and injury. By combining microRNA (miRNA) screening in LPS-treated myocardium with miRNA prediction targeting HIF1-α, we found that miR-299b-5p may serve as a regulator of HIF1-α. The reduction in miR-299b-5p levels in LPS-treated myocardium, compared to the control group, was reversed by baicalein treatment. The reverse transcription quantitative polymerase chain reaction, Western blotting, and dual-luciferase reporter gene analyses together identified HIF1-α as the target of miR-299b-5p in cardiomyocytes.

Conclusion:Baicalein mitigates SIC at the miRNA level, suggesting the therapeutic potential of it in treating SIC through the regulation of miR-299b-5p/HIF1-α/ferroptosis pathway. Please cite this article as: Zhou WY, Du JK, Liu HH, Deng L, Ma K, Xiao J, Zhang S, Wang CN. Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway. J Integr Med. 2025; 23(5):560-575.

Objective: Huachansu injection (HCSI), a promising anti-cancer Chinese medicine injection, has been reported to have the potential for reducing the toxicity of chemotherapy and improving the quality of life for colorectal cancer (CRC) patients. The objective of this study is to explore the synergistic and detoxifying effects of HCSI when used in combination with irinotecan (CPT-11).

Methods: To investigate the effect of HCSI on anti-CRC efficacy and intestinal toxicity of CPT-11, we measured changes in the biological behavior of LoVo cells in vitro, and anti-tumor effects in LoVo cell xenograft nude mice models in vivo. Meanwhile, the effect of HCSI on intestinal toxicity and the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) expression was investigated in the CPT-11-induced colitis mouse model. Subsequently, we measured the effect of HCSI and its 13 constituent bufadienolides on the expression of UGT1A1 and organic anion transporting polypeptides 1B3 (OATP1B3) in HepG2 cells.

Results: The combination index (CI) results showed that the combination of HCSI and CPT-11 exhibited a synergistic effect (CI < 1), which significantly suppressing the LoVo cell migration, enhancing G2/M and S phase arrest, and inhibiting tumor growth in vivo. Additionally, the damage to intestinal tissues was attenuated by HCSI in CPT-11-induced colitis model, while the increased expression of UGT1A1 in HepG2 cells and in mouse was observed.

Conclusion: The co-therapy with HCSI alleviated the intestinal toxicity induced by CPT-11 and exerted an enhanced anti-CRC effect. The detoxifying mechanism may be related to the increased expression of UGT1A1 and OATP1B3 by HCSI and its bufadienolides components. The findings of this study may serve as a theoretical insights and strategies to improve CRC patient outcomes. Please cite this article as: Jiang B, Meng ZY, Hu YJ, Chen JJ, Zong L, Xu LY, Zhang XQ, Zhang JX, Han YL. Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo. J Integr Med. 2025; 23(5):576-590.

Background:Electroacupuncture (EA) may affect the severity of hot flashes (HFs) associated with natural menopause and provide additional benefits for postmenopausal women. However, the evidence for its effectiveness in the management of early postmenopausal HFs remains inadequately understood.

Objective:We designed this trial to assess the efficacy and safety of EA for relieving early postmenopausal HFs.

Design, setting, participants and interventions:This randomized sham-controlled trial involved 72 women with HFs. The participants were divided equally into the intervention and control groups. The intervention group was treated with EA, while the control group was treated with sham acupuncture. The main acupoints used were Hegu (LI4), Guanyuan (RN4), Sanyinjiao (SP6), Taixi (KI3), Fuliu (KI7) and Shenshu (BL23). All participants received 18 treatment sessions, distributed across a 6-week period. The treatment was administered on three occasions per week, adhering to a fixed weekday schedule (Monday, Wednesday, Friday or Tuesday, Thursday, Saturday) with a minimum interval of one day between sessions. Each patient received a 12-week follow-up.

Main outcome measures:The HF score was the primary outcome. Participants documented the frequency and severity of HFs in a 7-day symptom diary, which provided data for calculating the HF score. Secondary outcomes were the Menopause Rating Scale (MRS), Menopause-Specific Quality of Life Questionnaire (MENQOL), Pittsburgh Sleep Quality Index (PSQI) and Traditional Chinese Medicine Syndrome Score Scale (TCMSSS), as well as estradiol (E2), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels.

Results:Both groups demonstrated significant reductions in HF scores after the treatment and during the follow-up (P < 0.001). Immediately after completion of the 6-week treatment cycle and at 12 weeks post-intervention, the HF scores were similar in both groups. At week 6, the intervention group showed significantly greater improvements in MRS, MENQOL (vasomotor, psychosocial, and physical), PSQI and TCMSSS scores (P < 0.05). The improvements in the MENQOL (vasomotor, and psychosocial) and PSQI total scores persisted through the follow-up (P < 0.05). However, the results showed no significant inter- or intragroup differences in sexual scores on the MENQOL (P > 0.05). EA did not significantly decrease E2, LH or FSH levels compared to placebo. The incidence of adverse events was similar in both groups.

Conclusion:EA does not significantly improve HFs in early postmenopausal patients. However, it enhances the quality of sleep and decreases menopausal symptoms across vasomotor, psychosocial and physical domains.

Trial registration:Chinese Clinical Trial Registry (http://www.chictr.org.cn); Trial ID: ChiCTR2300072002. Please cite this article as: Wang HX, Yu XT, Hu J, Chen JJ, Mei YT, Chen YF. Electroacupuncture for hot flashes in early menopause: A randomized sham-controlled trial. J Integr Med. 2025; 23(5):519-527.

Background
Spinal cord injury (SCI) survivors often experience constipation, which contributes to a reduced sense of well-being and a lower quality of life. Acupressure offers a non-pharmacological and non-invasive alternative therapy for treating constipation.

Objective
This study examined the effects of home-based acupressure on constipation and subjective well-being among SCI survivors.

Design, setting, participants and interventions
This randomized controlled trial randomly assigned 80 adults from Hong Kong with SCI to two study groups. Using a video demonstration filmed by a registered traditional Chinese medicine practitioner, the intervention group performed home-based acupressure (self-administered or caregiver-assisted) twice daily, 15 min/session, for 10 consecutive days. The control group performed manual light touching of the abdomen with the same frequency and duration as the intervention group. Both groups received defecation education through a structured booklet.

Main outcomes measures
The primary outcome was constipation severity. Secondary outcomes included bowel habits, psychological well-being, and quality of life. Focus group interviews were conducted after the intervention to collect subjective feedback from participants.

Results
Significant group-by-time interaction effects on constipation severity (P = 0.005) and quality of life (P = 0.001) revealed that home-based acupressure produced better results than the control. These treatment effects persisted at the one-month follow-up and continued to have a large effect size (Cohen’s d > 0.8). Compared to the control group, the acupressure group also had improvements in anxiety (Cohen’s d = 0.69) and depression (Cohen’s d = 0.72) at the end of the intervention period. Three qualitative categories were identified from the focus group interviews: improvements in bowel function and management; reduced psychological distress following relief from constipation; and acceptability of home-based acupressure.

Conclusions
Acupressure effectively relieves constipation, enhances psychological well-being, and improves quality of life in people with SCI. These data provide novel evidence supporting the use of home-based acupressure as an acceptable and effective therapy for treating constipation after SCI.

Trial registration: ClinicalTrials.gov (NCT05558657).

Objective:To explore the association between acupuncture during controlled ovarian hyperstimulation (COH) and the live birth rate (LBR) using different propensity score methods.

Methods:In this retrospective cohort study, eligible women who underwent a COH were divided into acupuncture and non-acupuncture groups. The primary outcome was LBR, as determined by propensity score matching (PSM). LBR was defined as the delivery of one or more living infants that reached a gestational age over 28 weeks after embryo transfer. The propensity score model encompassed 16 confounding variables. To validate the results, sensitivity analyses were conducted using three additional propensity score methods: propensity score adjustment, inverse probability weighting (IPW), and IPW with a "doubly robust" estimator.

Results:The primary cohort encompassed 9751 patients (1830 [18.76%] in the acupuncture group and 7921 [81.23%] in the non-acupuncture group). Following 1:1 PSM, a higher LBR was found in the acupuncture cohort (41.4% [755/1824] vs 36.4% [664/1824], with an odds ratio of 1.23 [95% confidence interval, 1.08-1.41]). Three additional propensity score methods produced essentially similar results. The risk of serious adverse events did not significantly differ between the two groups.

Conclusion:This retrospective study revealed an association between acupuncture and an increased LBR among patients undergoing COH, and that acupuncture is a safe and valuable treatment option. Please cite this article as: Zheng XY, Jiang ZY, Li YT, Li CL, Zhu H, Yu Z, Yu SY, Yang LL, Tang SY, Lü XY, Liang FR, Yang J. Association between acupuncture and live birth rates after fresh embryo transfer: A cohort study based on different propensity score methods. J Integr Med. 2025; 23(5):528-536.

Objective:To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2).

Methods:The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology.

Results:Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors.

Conclusion:EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.

Objective:Diabetes-induced gastrointestinal (GI) motility disorders are increasingly prevalent. Damage to the enteric nervous system (ENS), composed primarily of enteric neurons and glial cells, is an essential mechanism involved in these disorders. Although electroacupuncture (EA) has shown the potential to mitigate enteric neuronal loss, its mechanism is not fully understood. Additionally, the effects of EA on enteric glial cells have not been investigated. Enteric neural precursor cells (ENPCs) contribute to the structural and functional integrity of the ENS, yet whether EA enhances their differentiation into enteric neurons and glial cells remains unexplored. This study investigates whether EA promotes ENS repair through enhancing ENPC-derived neurogenesis and gliogenesis and elucidates the potential molecular mechanisms involved.

Methods:Transgenic mice were used to trace Nestin+/nerve growth factor receptor (Ngfr)+ENPCs labeled with green fluorescent protein (GFP) in vivo. Mice were randomly divided into four groups: control, diabetes mellitus (DM), DM + sham EA, and DM + EA. The effects of EA on diabetic mice were evaluated by GI motility, ENS structure, and ENPC differentiation. Glial cell line-derived neurotrophic factor (GDNF)/Ret signaling was detected to clarify the underlying molecular mechanisms.

Results:EA alleviated diabetes-induced GI motility disorders, as indicated by reduced whole gut transit time, shortened colonic bead expulsion time, and enhanced smooth muscle contractility. Furthermore, EA attenuated diabetes-induced losses of enteric neurons and glial cells, thereby restoring ENS integrity. Notably, EA reversed the diabetes-induced decrease in ENPCs and significantly increased the absolute number and the proportion of ENPC-derived enteric neurons. However, immunofluorescence analyses revealed no colocalization between EA-induced glial fibrillary acidic protein+glial cells and GFP-labeled ENPCs. Mechanistically, GDNF/Ret signaling was elevated in intestinal tissues and upregulated in ENPCs in EA-treated diabetic mice.

Conclusion:EA facilitates ENS repair by promoting Nestin+/Ngfr+ENPC differentiation into enteric neurons via upregulation of GDNF/Ret signaling, and driving enteric gliogenesis from non-Nestin+/Ngfr+ENPCs. These findings highlight EA's role in ameliorating diabetes-induced GI dysmotility through ENPC-derived ENS restoration. Please cite this article as: Guo JL, Liu S, Ding SJ, Yang X, Du F. Electroacupuncture at ST36 improves gastrointestinal motility disorders by promoting enteric nervous system regeneration through GDNF/Ret signaling in diabetic mice. J Integr Med. 2025; 23(5):548-559.

Objective

To describe the clinical features and effectiveness of Xuanbai Shengmai Decoction (XB, a compound Chinese herbal medicine) on disease progression, clinical effect and viral RNA shedding in COVID-19 cases.

Methods

We collected demographic and clinical information of 212 COVID-19 cases from December 2022 to January 2023, and divided these cases into two groups based on whether XB was used or not. Survival curves in the two groups were estimated by the Kaplan-Meier method. A smoothing approximation of time-to-event distributions was created based on a log-rank test and a restricted mean survival time model, and the Gaussian density estimation method. In addition, the effect of XB treatment on survival time was assessed using a series of Cox proportional hazards models.

Results

Of all 212 COVID-19 cases, there were respectively 63 and 149 cases reported in XB group and non-XB group. Of those, 128 (60.4%) were male, with median age of 75.00 years, and 72.6% had one or more underlying medical conditions. The most common symptoms on admission were cough (64.6%), fever (39.6%), wheezing (27.8%) and sputum (13.2%). In addition, the gender, age group distribution, smoking, and drinking between two groups were of no significant difference (P > 0.05). However, the clinical characteristics and CT findings in XB group were more serious than those in non-XB group. Nevertheless, the hazard of death in XB group was lower than that in non-XB group, especially on severe cases. Treatment with XB significantly protected against adverse outcomes, shorten the time of viral RNA shedding. Moreover, interventional therapy of XB within 1-2 days after hospital admission is confirmed with particularly effectiveness.

Conclusion

Treatment of XB is effective for COVID-19 cases, particularly in reducing the mortality rate of severe cases, suggesting that XB may be used as an alternative treatment of SARS-COV-2 infection. Please cite this article as: Liu TW, Zhang SW, Jiang H, Yang SW, Guo YJ, Ding MY, Li XC, Xu J, Lu HT, Ye HR, Hu YH, Li R, Wei YM, Song MF, Wang S, Zhang J, Feng QS, Xu XL. Effectiveness of Xuanbai Shengmai Decoction, a compound Chinese herbal medicine, on disease progress and viral RNA shedding in COVID-19 patients: A retrospective study of medical chart in China. J Integr Med. 2026; 24(1):115-124.

Objective

To assess whether electroacupuncture (EA) can facilitate the restoration of the intestinal mucosal barrier in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) by regulating adherens junctions through mast cells (MCs) and microRNAs.

Methods

Forty Sprague-Dawley rats were divided into control group and IBS-D group. Rats were given Senna solution via gavage and subjected to a 14-day chronic unpredictable mild stress procedure. Subsequently, rats in the IBS-D group were assigned to a model group, an EA group, and an EA + MC agonist group. Visceral pain threshold and diarrhea index (DI) were measured. Transmission electron microscopy was used to observe the ultrastructure of MCs. Enzyme-linked immunosorbent assay (ELISA) was used to measure tryptase and diamine oxidase (DAO) levels. Western blotting and quantitative polymerase chain reaction (qPCR) techniques were used to evaluate the quantities of E-cadherin and α-catenin. Immunohistochemistry and ELISA were used to assess the levels of F-actin and vinculin. microRNAs from the colon were sequenced, and qPCR was used to validate the sequencing results. In vitro, Caco-2 cells were used to establish the intestinal epithelium model. After transfection with miR-494-3p mimics, qPCR was performed to measure the expression of microRNAs, E-cadherin and α-catenin; the transmittance of fluorescein isothiocyanate-dextran was detected to measure permeability of the cell layer.

Results

In the model group, DI, and tryptase and DAO concentration increased; body weight, visceral pain threshold and the expression of E-cadherin, α-catenin, F-actin and vinculin were significantly decreased compared to the control group. This pattern was reversed in the EA group. No significant difference was found between the EA + MC agonist group and the model group. Sequencing revealed that the expression of miR-541-5p and miR-494-3p was significantly higher in the model group and lower in the EA group. Enrichment analyses revealed that the majority of enrichments were associated with adherens junctions. Spearman's correlation tests indicated that the expression of miR-541-5p and miR-494-3p had a positive correlation with serum DAO and colonic tryptase levels, while showing a negative correlation with E-cadherin level. After microRNA mimic transfection, the expression of miR-494-3p and the barrier permeability were significantly increased, and the expression of E-cadherin was significantly decreased.

Conclusion

In rats with IBS-D, EA may help repair the intestinal barrier function by modulating adherens junctions and cytoskeletal components through the inhibition of MCs; miR-494-3p may play pivotal roles in this process. Please cite this article as: Hou YJ, Zheng HB, Wang K, Jiang HL, Chen Y, Wang L, Zheng QH, Li Y, Zhou SY. Electroacupuncture repairs intestinal mucosal barrier in rats with diarrhea-predominant irritable bowel syndrome by regulating adherens junctions through mast cells and microRNAs. J Integr Med. 2026; 24(1):125-136.

Objective: Laboratory tests are commonly used in Korean medicine (KM) clinics to monitor the safety of herbal medicine (HM). Although the incidence of herb-induced liver injury (HILI) in Republic of Korea has been reported, there is a lack of data from KM clinics, which account for over 90% of KM institutions. This absence is due to the lack of a systematic pharmacovigilance system for HMs. To partially understand this issue, this study investigated changes in liver function test (LFT) and renal function test (RFT) after HM prescriptions in primary settings.
Methods: This retrospective analysis utilized laboratory test results, including complete blood count, LFT and RFT, collected from 238 KM clinics across the Republic of Korea. The study population comprised patients who underwent laboratory testing before and after HM treatment between March 2020 and November 2021. We compared laboratory test results using paired t-tests or Wilcoxon signed-rank tests. Subgroup analyses were conducted by sex and elapsed time between tests. The McNemar test was used to compare the proportions of cases with abnormal LFT and RFT levels according to lifestyle habits and comorbidities. Additionally, the incidence of liver injury was estimated by identifying cases with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels exceeding five times the upper limit of normal after HM prescription.
Results: A total of 2791 cases were included in the analysis. The levels of AST and ALT decreased significantly after HM prescription (P < 0.0001). This result was consistent in subgroups stratified by sex and for test intervals of within 30 and 60 days (P < 0.05). The proportion of cases with abnormal AST and ALT levels significantly decreased after HM prescription (P < 0.001). Out of 2791 cases, only 2 (0.07%) were identified as having liver injury after HM prescription, but causality was not confirmed.
Conclusion:The findings suggest that the use of HM in KM clinics in Republic of Korea is generally safe. While a small number of HMs may be associated with liver injury, causality remains uncertain. Establishing a national pharmacovigilance system is crucial for accurately monitoring the incidence and risk factors of HILI. Please cite this article as: Cho E, Ko MM, Yang C, Kim S. Safety of herbal medicines in Korean medicine clinics in Republic of Korea: A nationwide retrospective longitudinal cohort study. J Integr Med. 2026; 24(2):192-200.

Objective: Xinyang Tablet (XYAT) and Xinyin Tablet (XYIT) have been used to treat chronic heart failure (CHF) for 20 years. This study investigated their pharmacodynamic material basis and underlying mechanisms of action.

Methods: Ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS) was used to identify the components of XYAT and XYIT, and to profile their metabolites in plasma and urine samples from both rats and human volunteers. Furthermore, the prototype compounds and their pharmacokinetics were evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Network pharmacology predicted potential targets and pathways, which were subsequently validated through flow cytometry and Western blot. The efficacy of XYAT, XYIT and their active components was evaluated in oxidative stress and cardiotoxicity models.

Results: A total of 162 and 130 compounds were detected in XYAT and XYIT, respectively; among these, 148 from XYAT and 119 from XYIT were structurally identified. A validated HPLC-MS/MS method quantified 20 key exposure components, five of which showed high systemic exposure and underwent pharmacokinetic analysis. Pharmacokinetic results indicated that the systemic exposure of most compounds was higher for XYAT than for XYIT. Using network pharmacology, seven candidate active compounds were identified, along with their predicted therapeutic targets and associated signaling pathways. Flow cytometry and Western blot confirmed that XYAT, XYIT, and their bioactive components alleviate CHF by modulating calcium signaling and phosphoinositide 3-kinase/protein kinase B signaling. Pharmacodynamic assays demonstrated that XYAT provides protection against hydrogen peroxide-induced injury, while XYIT mitigates doxorubicin-induced cytotoxicity. Further validation confirmed that 20(S)-ginsenoside Rg2 and 20(R)-ginsenoside Rh1 effectively reduced the H2O2-induced oxidative stress, while 20(S)-ginsenoside Rg2 and calycosin-7-O-β-d-glucoside significantly protected against doxorubicin-induced cytotoxicity.

Conclusion:These findings provide mechanistic insights into the pharmacodynamic material basis and anti-CHF mechanisms of XYAT and XYIT. The integrated strategy established herein offers robust evidence that the superior systemic exposure of key components underpins the rationale for XYAT's formulation and warrants its continued development in modern cardiology. Please cite this article as: Lan YL, Chen SM, Dai BX, Wu CS, Wei Y, Yang L, Yan JL, Guo YQ, Wang DW, Li QG, Yang ZQ, Xian SX, Yuan TH. Bioactive components of Xinyang and Xinyin tablets for treating chronic heart failure: pharmacokinetics, network pharmacology and experimental validation. J Integr Med. 2026; 24(2):265-278.

Objective: This study develops a core outcome set (COS) for clinical research concerning Chinese medicine (CM) dampness syndrome (COS-CMDS) that might improve heterogeneity of outcomes, reporting, and inadequate attention to the CM characteristic outcomes in clinical research on CM dampness syndrome.

Methods: An initial outcome pool was constructed based on a systematic review of clinical studies related to CM dampness, registered trials, and semi-structured interviews with patients and healthcare professionals. Various stakeholders were invited to participate in a 2-round Delphi survey to scrutinize the important outcomes. A consensus meeting was held to determine the final COS-CMDS.

Results: We identified 1904 studies and 73 registered trials in the systematic review. Six patients and seven healthcare professionals were invited to participate in a semi-structured interview. Then, 541 outcomes were extracted, of which 397 were physicochemical. After combining certain outcomes (especially the physicochemical outcomes) and excluding those with weak relevance by discussion, 26 outcomes were included in round 1 of the Delphi survey. Round 1 was completed by 82.89% of participants, and 22 outcomes were carried on to round 2. Round 2 was completed by 92.06% of participants, and 14 outcomes achieved consensus for inclusion in the COS. Nineteen stakeholders attended the consensus meeting, voted, and discussed the final COS. It included evaluation of dampness syndrome, CM syndrome assessment, effective response, validated laboratory outcomes of CM dampness syndrome, and adverse events.

Conclusion: The COS-CMDS provides a reference for the selection and reporting of outcomes in clinical research concerning CM dampness syndrome, embodying the characteristics of CM. Please cite this article as: Qiu XY, Tang Q, Cheng T, Cao WC, Liu BQ, Wen ZH, Li G. Developing a core outcome set for clinical research on Chinese medicine dampness syndrome. J Integr Med. 2026; 24(2):201-209.

Background: Auriculotherapy is a simple, convenient, nonpharmacological option that has shown positive effects for insomnia patients, but its efficacy and safety remain unknown.

Objective: The aim of this study is to evaluate the efficacy and safety of auricular therapy for insomnia.

Design, setting, participants and intervention: An 18-week (2-week screening, 4-week treatment, and 12-week follow-up), recruiter- and assessor-blinded, randomized, sham-controlled trial was performed. Patients were recruited from outpatient settings at three clinical centers in China from 2 February 2023 to 26 January 2024. Participants had insomnia for more than 3 months and met the criteria classified in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). Patients were randomly assigned in a 1:1 ratio to receive auricular therapy (AT) or sham AT (SAT) for 4 consecutive weeks, twice a week, and once every 3 days.

Main outcome measures: Primary outcome was the response rate at week 4 after treatment, defined as the percentage of patients with at least a 50% reduction in Pittsburgh Sleep Quality Index (PSQI) from baseline. Secondary outcomes consisted of response rates at other time points, PSQI and 4 related scales, actigraphy-recorded sleep efficiency, sleep arousal frequency, and total sleep time.

Results: A total of 234 participants were screened, and 156 patients (122 female [78.2%]; mean [standard deviation] age, 37.2 [13.5] years) were included in the intention-to-treat analysis, with 78 participants randomized to each group. A total of 117 participants (75%) were followed up for 3 months. The AT group had a higher response rate at week 4 than the SAT group (39.73% [29/73] vs 23.29% [17/73], P = 0.03), and the response rates for the AT and SAT groups at week 2 were 28.38% (21/74) and 13.33% (10/75), respectively (P = 0.02). The differences between the two groups in the PSQI at each time point (P < 0.05) and the Insomnia Severity Index at weeks 4 and 12 (both P = 0.03) were also statistically significant. The other partial outcomes also showed statistically significant differences. Adverse events occurred in 2 cases in the AT group (2.60%).

Conclusion: Four-week AT treatment was an effective and safe alternative therapy for insomnia, although the difference with the SAT treatment did not reach the minimal clinically important difference. Adverse events were mild or transient.

Trial registration: Chinese Clinical Trial Registry, identifier ChiCTR2200065187. Please cite this article as: Chen H, Zhang XF, Yuan ZC, Wang XS, Gao YB, Li XX, Zhang JC, da Silva Oliveira MD, de Barros Nunes CA, Liu J, She YF. Efficacy and safety of auriculotherapy for insomnia disorder: A randomized controlled trial. J Integr Med. 2026; 24(2):174-181.

Objective: Chronic cerebral hypoperfusion (CCH) can cause long-term changes in gene expression and increase susceptibility to spatial memory impairment, in which the histone acetylation plays a crucial role. Studies have found that electroacupuncture (EA), a non-drug therapy, is beneficial to alleviate spatial memory impairment. However, the underlying mechanism of the histone acetylation is not yet completely clear. The goal of this study was to investigate the mechanisms by which EA stimulation of acupoints on the head region ameliorates histone acetylation in CCH.
Methods: The spatial memory of CCH rats were evaluated before and after the EA intervention using two behavioral tests: Barnes maze (before EA treatment) and Morris water maze (after EA treatment). To further investigate the mechanism by which EA improves spatial memory, Western blotting, real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR), chromatin immunoprecipitation (ChIP), Golgi staining, and neuroelectrophysiology were used. Furthermore, we used Adeno-associated virus vector expressing cyclic AMP response element-binding protein (CBP)/E1A binding protein p300 (P300)-specific short hairpin RNAs (sh CBP/P300) to inhibit the acetylation levels of histones H3 and H4 in the hippocampus.
Results: CCH rats showed changes in spatial memory, including a decline in acquisition and maintenance. Compared to the sham group, there were significantly lower levels of total histone acetylation in the CCH rats and the acetylation levels of histone H3 and H4 in the hippocampus of rats decreased in the CCH group. The ChIP experiment results showed that the enrichment of acetylation tags of histone 3 at lysine 9 occurred at the promoter sites of Finkel-Biskis-Jinkins osteosarcoma oncogene (c-Fos), early growth response 1 (Egr1), and activity-regulated cytoskeleton-associated protein (Arc). Western blotting and RT-qPCR detection showed that the transcriptional and expression level of c-Fos and Egr1 decreased. Golgi staining showed that the density of dendritic spines decreased in the hippocampal cornu ammonis 1 area. In contrast, with the EA intervention, the behavior performance and molecular biological indexes were improved. Furthermore, we observed a significant decrease in the histone H3 and H4 acetylation after inhibition of CBP/P300 expression with sh CBP/P300, which resulted in the abrogation of EA's beneficial effect.
Conclusion: EA can improve spatial memory impairment in CHH rats by regulating the expression of the hippocampal imprinted genes c-Fos and Egr1 and by enhancing synaptic plasticity through the epigenetic modification of histone H3 and H4 acetylation. Please cite this article as: Ding YY, Wang WJ, Chen LW, Yang MG, Dai YL, Li R, Cao YJ, Wang SN, Wang LM, Wu B, Chen LM, Liu WL. Electroacupuncture regulates histone acetylation to improve spatial memory impairment in rats with chronic cerebral hypoperfusion. J Integr Med. 2026; 24(2):224-237.

Objective: Gastric ulcers are a global health issue, often occurring in the stomach or duodenum and causing tissue necrosis. Talinum paniculatum (Jacq.) Gaertn (Erva-gorda) is used in traditional medicine for treating gastric ulcers. This study aimed to assess the gastroprotective effects of the ethanol-soluble fraction from T. paniculatum leaves (ESTP) in rodents.
Methods:The gastroprotective potential of ESTP was evaluated at 30, 100, and 300 mg/kg taken orally, or 30 mg/kg intraperitoneally against gastric lesions induced by a 60% ethanol solution containing 0.3 mol/L hydrochloric acid, in mice. Histological sections were examined after hematoxylin-eosin staining and their mucin content was determined using the periodic acid-Schiff method. Oxidative stress markers, including levels of reduced glutathione and lipid hydroperoxide, as well as inflammatory parameters such as myeloperoxidase activity and nitrite levels, were analyzed. Mechanistic studies involved pretreating the mice with N-ethylmaleimide (NEM), N-nitro-l-arginine methyl ester (L-NAME), and indomethacin.
Results: ESTP at 300 mg/kg orally and 30 mg/kg intraperitoneally significantly reduced ethanol/HCl-induced gastric injury. It decreased lipid hydroperoxide levels but did not increase levels of reduced glutathione. Myeloperoxidase activity and nitrite levels were reduced. However, ESTP did not restore mucin levels. Pretreatment with indomethacin nullified the protective effects of ESTP while NEM and L-NAME did not.
Conclusion: ESTP demonstrated a remarkable gastroprotective effect, as indicated by reductions in inflammatory and oxidative mediators. The observed decline in mucin activity, coupled with the absence of an effect following indomethacin pretreatment, implies a potential inhibition of the cyclooxygenase activity by the extract. These findings collectively support the traditional use of the species for gastrointestinal protection and highlight its potential as a therapeutic agent for managing gastric ulcers. Please cite this article as: Pegoraro Correa KG, do Carmo Barroso de Siqueira M, Zanovello M, Martins Belmudes M, de Souza P, Gasparotto Junior A, Boeing T. Gastroprotective activity of Talinum paniculatum (Jacq.) Gaertn. in mice: An ethnopharmacological validation. J Integr Med. 2026; 24(2):279-286.

Objective: Non-small cell lung cancer (NSCLC), a leading cause of cancer-related mortality, presents a poor prognosis due to its tendency to metastasize and its resistance to standard therapies. Montanine (MTN), a naturally occurring alkaloid, has recently shown potential as an anticancer agent. However, the specific mechanisms through which it exerts its anticancer effects are still largely unknown. This study investigates the anti-NSCLC potential of MTN by utilizing integrative network pharmacology alongside in vitro and in vivo experimental validations.

Methods: Genes targeted by MTN in NSCLC were identified and subjected to functional enrichment analysis to elucidate the most enriched signaling pathways. A protein-protein interaction network was constructed to identify the interactions of potential targets. Adrenoceptor β2 (ADRB2) expression in lung cancer was analyzed using data from The Cancer Genome Atlas and Gene Expression Omnibus datasets. The effects of MTN on NSCLC cell lines, including migration, proliferation, viability and apoptosis, were assessed in vitro. MTN-related mechanisms were investigated using quantitative reverse transcription-polymerase chain reaction and Western blotting. Furthermore, an in vivo lung cancer metastasis experiment was performed in rats using a tail vein assay.

Results: MTN at nontoxic doses significantly reduced cell migration and lung colonization in an in vivo metastasis study (P < 0.05). Network pharmacology revealed 29 targets of MTN in NSCLC, highlighting ADRB2 as a primary target linked to poor prognosis in lung cancer. In vitro studies confirmed that MTN notably upregulated ADRB2 expression and downregulated epithelial-mesenchymal transition (EMT) signaling pathways, which was further enhanced by terbutaline sulfate, an ADRB2 activator.

Conclusion: MTN is a promising therapeutic agent for NSCLC by suppressing the migration via ADRB2 and EMT mechanisms. Please cite this article as: Iksen I, Singharajkomron N, Wongtayan A, Wattanathamsan O, Choonhapan A, Wademonkolgorn S, Nguyen HM, Hoang THX, Nguyen HT, Pongrakhananon V. Unveiling the antimetastatic activity and molecular mechanism of montanine in lung cancer cells via the integration of network pharmacology approaches with in vitro and in vivo investigations. J Integr Med. 2026; 24(2):253-264.