ObjectiveUnder the background of policy guidance and technological development, the Multi-RevRobot for the translation of clinical evidence of traditional Chinese medicine (TCM) was developed to enhance the efficiency and applicability of clinical evidence translation in TCM. MethodsA prototype of Multi-RevRobot was designed and developed. This involved components such as the perception system, control system, execution system, power system, and interaction system. Universal model interfaces were integrated to connect with vertical large models and knowledge bases, enabling intelligent interaction. The artificial potential field method was combined with reinforcement learning to achieve efficient coordination between the robot’s global path planning and local obstacle-avoidance decision-making. This allows the robot to be deployed and applied in various scenarios. ResultsMulti-RevRobot features intelligent interaction, report generation, and multi-scenario adaptability. It provides a practical solution for TCM clinical evidence translation and plays corresponding roles in various scenarios. ConclusionMulti-RevRobot is expected to serve as a clinical and research assistant for doctors, researchers, patients, and other groups. It can improve the efficiency of TCM-related work and facilitate the intelligent and efficient translation and application of TCM evidence.

This study aimed to construct an evidence chain for the efficacy of Shuxuening Injection(SXN) in the treatment of unstable angina pectoris(UAP) and clarify its efficacy and underlying mechanisms. Eight major Chinese and English databases, including CNKI, VIP, Wanfang, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science, were systematically searched to collect clinical studies, animal experiments, cell experiments, and molecular experiments on SXN for UAP. Two researchers independently screened the literature and extracted data. Meta-analysis or descriptive analysis was used for data integration. The TCM evidence chain construction method was applied to establish evidence chains, which were then evaluated. A total of 2 evidence chains were constructed, incorporating 64 clinical studies, 12 animal experiments, 11 cell experiments, and 86 outcome indicators. The evidence chains elucidated the efficacy and mechanisms of SXN for UAP from 2 dimensions: improvement of myocardial ischemia and protection of cardiac function. SXN exerted a synergistic effect on the core pathological processes of UAP through multiple mechanisms, including regulating oxidative stress, promoting angiogenesis, modulating inflammation and matrix remodeling, inhibiting apoptosis, and balancing endoplasmic reticulum stress. SXN demonstrated efficacy in the treatment of UAP. However, due to the limitations in the quantity and quality of included studies, the robustness of the evidence chains was insufficient. High-quality clinical and basic research is required to further verify its core mechanisms. Additionally, it is recommended that subsequent studies include more indicators reflecting plaque stability and thrombosis in the selection of clinical outcome indicators.

Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targeted therapies due to the absence of hormone receptors and HER2 expression, resulting in poor clinical outcomes and limited treatment options. Identifying novel vulnerabilities is therefore critical to advancing TNBC therapeutics. Mitochondrial metabolism has emerged as a key regulator of cancer cell survival and proliferation, with serine hydroxymethyltransferase 2 (SHMT2) playing a central role in mitochondrial one-carbon metabolism by supplying one-carbon units for nucleotide biosynthesis and maintaining redox homeostasis. Despite its established importance in cancer metabolism, the functional role and therapeutic potential of SHMT2 in TNBC remain underexplored. Here, we demonstrate that gambogic acid (GA), a natural product with reported anticancer properties, exerts potent and selective cytotoxicity against TNBC cells by covalently targeting SHMT2. GA binds specifically to the critical cysteine residue Cys241, inhibiting SHMT2 enzymatic activity and disrupting mitochondrial function. This leads to bioenergetic collapse, activation of the Nrf2/HO-1 axis, iron overload, and induction of ferroptosis, a non-apoptotic form of cell death increasingly recognized for its therapeutic potential. Our integrative chemoproteomic and mechanistic studies reveal a novel SHMT2-mitochondria-Nrf2/HO-1-ferroptosis axis driving GA's anti-TNBC activity. Moreover, SHMT2 overexpression in TNBC correlates with tumor aggressiveness and poor prognosis, underscoring its role as a metabolic oncogene and promising drug target. These findings establish GA as a novel covalent SHMT2 inhibitor and provide a new framework for exploiting metabolic vulnerabilities to overcome TNBC treatment resistance.

ObjectivesThe inconsistent reporting of clinical trial results in patients with atrial fibrillation (AF) hinders the comparison of findings. Developing a core outcome set (COS) in studies evaluating traditional Chinese medicine (TCM) for AF and recommending measurement instruments and time points may help standardize the selection, reporting, and measurement of outcomes in clinical trials.MethodsLiterature and registered trials were retrieved to systematically collect outcomes. Physician questionnaire surveys and semi-structured patient interviews were conducted to collect outcomes of clinical interest. These outcomes were standardized and compiled into a preliminary outcome pool. Consensus criteria were established in advance. Through two rounds of Delphi surveys and consensus meetings, perspectives from multiple stakeholder groups were gathered to establish a COS for TCM for AF (COS-TCM-AF).ResultsA total of 87 individuals participated in the Delphi survey, with 70 completing both rounds. During the consensus meeting, 19 stakeholders determined that seven core outcomes should be involved in the COS-TCM-AF, including AF episode frequency, AF episode duration, AF burden, TCM symptom-palpitation, thromboembolic (TE) event rate, AF recurrence rate, and incidence of acute heart failure (HF)/acute exacerbation of chronic HF. Among these, AF episode frequency and AF episode duration applied only to patients with paroxysmal AF.ConclusionThis COS comprehensively addresses multiple aspects including AF episodes, patient symptoms, complication risks and long-term prognosis. It also recommends measurement instruments and time points. Its implementation will contribute to facilitating the comparison of similar studies and provide a reference for selecting and measuring outcomes.

In recent years, China's new round of institution reform has further optimized the drug regulatory system. Relevant departments and institutions involved in traditional Chinese medicine (TCM) regulation have been strengthened. TCM regulatory science, as an emerging interdisciplinary field, has received high regard and experienced rapid development, significantly enhancing TCM regulatory capabilities. Simultaneously, accelerated progress in emerging technologies and production innovation for TCM drug discovery, coupled with the implementation of the National Major Scientific and Technological Special Project for ''Significant New Drugs Development'' and its translational achievements, have led to a historic turning point in the development of innovative natural TCM drugs over the past five years. Driven by the dual engines of ''regulatory science'' and ''policy restructuring'', the development of new TCM drugs has entered a fast lane. Both the quantity and quality of investigational new drug (IND) and new drug application (NDA) registrations and approvals for new natural TCM drugs have shown rapid growth, effectively meeting the public's health demands for TCM products and unmet clinical needs of patients. This study focuses on the development of new TCM drugs during the significant historical phase from 2021 to 2025. It provides a comprehensive overview of new TCM and natural drug applications and regulatory reviews over the past five years, delves into the implementation of the National Drug Regulatory Science Action Plan, and highlights the importance of TCM regulatory science as an emerging interdisciplinary field in accelerating the creation of new TCM drugs. It systematically summarizes the effects of regulatory policies and regulations, the reform of TCM registration classification, specialized TCM registration provisions, and incentive measures such as the National Major Scientific and Technological Special Project for ''Significant New Drugs Development''. Based on an international perspective, it provides a focused review of recent highlights in TCM new drug development and regulation. This holds significant importance for promoting breakthroughs in TCM new drugs across more disease areas and advancing the international coordination of TCM regulation. The challenge faced in managing the registration of new TCM drugs lies in resolving the conflict between TCM theory and modern drug attributes, while balancing the rapid advancement of traditional medical theory and emerging technologies with the robustness of the drug regulatory framework. In the future, actively advancing research and translation in TCM regulatory science, innovatively establishing benefit-risk assessment systems and standards for new TCM drugs, and accelerating the development of a globally leading regulatory system with Chinese characteristics that aligns with the unique nature of TCM will be particularly crucial for global coordination of TCM regulatory policies, and the modernization and internationalization of TCM.

OBJECTIVES:To evaluate the status and methodological quality of randomized controlled trials published in 2024 on Chinese patent medicines and Classic Traditional Chinese Medicine Prescriptions, providing evidence for clinical practice and policy. METHODS:We systematically searched multiple Chinese and English databases and trial registries for randomized controlled trials (RCTs) on Chinese patent medicines (CPMs) and Classic Traditional Chinese Medicine Prescriptions (CTCMPs) published in 2024. Two researchers independently screened studies, extracted data, and assessed methodological quality using the Cochrane RoB tool. Inter-rater reliability was evaluated using Kappa statistics and intraclass correlation coefficient. Spearman's correlation and Wilcoxon rank-sum tests were performed to analyze factors influencing methodological quality. RESULTS:In 2024, 1874 RCTs were included (1550 CPM, 324 CTCMP). Circulatory and digestive diseases predominated in CPM and CTCMP studies, respectively. Two-arm "Chinese medicine plus Western medicine" designs were mainstream. CPM RCTs favored physical/chemical outcomes, while CTCMP RCTs prioritized symptoms/signs outcomes; 169 patient-reported outcomes were identified. Most studies had small samples (100 cases) and were single-center. Methodological quality revealed adequate randomization but serious deficiencies in allocation concealment and blinding. Ethics approval (CPM≈68.5%, CTCMP≈61.1%) and trial registration (CPM≈3.8%, CTCMP≈0.9%) were suboptimal. Funding, higher journal IF, and multicenter design were positively associated with ROB scores. CONCLUSIONS:This evidence mapping reveals a significant disconnect between the quantity and quality of randomized controlled trials in Traditional Chinese Medicine. Persistent methodological weaknesses undermine evidence reliability. Future research should prioritize methodological rigor, adequate statistical power, and prospective trial registration. There is an urgent need to develop a dedicated evaluation framework that captures both methodological quality and clinical value.

This study aims to explore the connection between the Monocyte to High-Density Lipoprotein Cholesterol Ratio (MHR) and the formation of carotid artery plaque (CAP) in individuals who have experienced a cerebral infarction (CI). Additionally, it examines the relationship between CAP and varying blood pressure and glucose metabolism stratifications. The investigation involved 10,627 individuals with cerebral infarction. Participants were categorized based on their blood pressure levels and glucose metabolism profiles, and then sorted into tertiles according to their MHRs. Logistic regression analysis was used to assess the relationship between MHR and carotid plaque in CI patients, adjusting for potential confounders and applying FDR correction. Discrimination performance was evaluated using ROC curves, NRI, and IDI. Restricted cubic splines and threshold analysis were employed to explore dose-response relationships and identify inflection points. MHR demonstrated a significant positive association with carotid artery plaque (CAP) in patients with cerebral infarction. For each one-standard deviation increase in standardized MHR, the adjusted OR was 1.154 (95

BackgroundWhile Western medicine is increasingly investigating sex- and gender-specific differences in health and disease, and despite TCM theory and practice placing particular emphasis on individual differences—including sex- and gender-related characteristics, research on sex- and gender- sensitive medicine in TCM remains underexplored.ObjectiveWe conducted a scoping review to map and synthesize the existing evidence on sex- and gender-specific differences in the efficacy and safety of TCM interventions and to analyze possible underlying mechanisms.MethodsThe scoping review followed the JBI guidance. Six Chinese and English databases (CNKI, WF, VIP, SinoMed, PubMed, and Web of Science) were searched from inception to July 2025 for preclinical and clinical studies. Key information was extracted from the included studies, and data were synthesized using descriptive statistics and systematic narrative synthesis. GraphPad Prism 10.0 was used to generate figures.ResultsDatabase searches identified 6,720 records; after removing 250 duplicates, 6,470 records were screened by title and abstract, and 2,417 proceeded to full-text eligibility assessment. Ultimately, 16 studies were included, comprising randomized controlled trials, animal experiments, non-randomized controlled trials, and single-arm trials. Conclusions drawn from the original studies indicated that changes in all relevant outcome measures were associated with sex. Sex-specific differences in TCM efficacy were observed across herbal, acupuncture, and combined interventions. Female animals demonstrated predominant benefits in bone metabolism, whereas female human participants showed greater benefits in pain perception, emotional regulation, neurological recovery, and pulmonary functional outcomes. Male animals exhibited more pronounced gut microbiota responses to metabolic interventions, while male human participants showed stronger effects in obesity-related outcomes and sensorimotor responses. These divergent patterns likely reflect sex-related differences in pharmacokinetics, gut-brain axis interactions, and neuroendocrine mechanisms. None of the included studies examined gender-related sociocultural factors.ConclusionThis review highlights a persistent theoretical and methodological gap in TCM research, which has yet to fully integrate sex- and gender-sensitive medicine principles. The limited high-quality clinical evidence underscores the need for rigorous sex-informed trials to evaluate efficacy across sexes. These findings support the integration of sex as a key determinant in TCM clinical decision-making, alongside syndrome differentiation, to advance precision medicine and improve personalized therapeutic outcomes.Systematic Review RegistrationDOI: 10.17605/OSF.IO/QABTY.

Diabetic kidney disease (DKD) is a prevalent and serious complication of diabetes and a leading cause of end-stage renal disease (ESRD). As the central organelles for cellular energy metabolism, mitochondria play a pivotal role in the pathogenesis of DKD. Structural and functional impairments of mitochondria trigger multiple renal pathological processes, such as oxidative stress, apoptosis, chronic inflammation, and fibrosis. Mitochondrial dynamics are crucial for maintaining mitochondrial integrity, and their involvement in the progression of DKD is increasingly recognized. Nevertheless, comprehensive reviews addressing the relationship between mitochondrial dynamic homeostasis and DKD are still lacking. This review systematically summarizes the pivotal role of imbalanced mitochondrial dynamics in the pathogenesis and progression of DKD. It details the underlying regulatory mechanisms and stage-specific pathological contributions across different renal cell types, discusses potential diagnostic and therapeutic applications, and evaluates the prospects of natural products that target mitochondrial dynamics in DKD. By integrating current evidence, this work aims to provide a theoretical foundation and strategic guidance for innovative drug development and precision medicine in DKD.

Background:Despite increasing global attention, significant knowledge gaps remain regarding the incidence of adverse outcomes associated with mpox. To support the development of World Health Organization (WHO) mpox guidelines, this systematic review and meta-analysis evaluated the incidence of complications among patients with mpox. Methods:We searched Medline, Embase, CENTRAL, CINAHL, Global Health, medRxiv, bioRxiv, and SSRN from database inception to December 20, 2025, for studies reporting complications in patients with laboratory-confirmed mpox of all ages. Paired reviewers independently screened studies, extracted data, and assessed risk of bias. We conducted proportional meta-analyses using the inverse variance method fixed-effect model with the Freeman-Tukey double arcsine transformation and evaluated the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. We classified mpox as severe or non-severe based on the need for hospitalization or the study's criteria. We registered the protocol with PROSPERO (CRD42024595685). Findings:Of 4566 records, 170 studies with 127,564 patients (mean age 6.9-43.0 years) proved eligible. Among patients with non-severe mpox, serious complications were rare. Mortality, intensive care unit admission, sepsis, pneumonia, encephalitis, epiglottitis, myocarditis, gastrointestinal bleeding, and pleural effusion all occurred in ≤0.5% of patients (moderate to high certainty evidence). Urinary retention, mechanical ventilation, urethritis, gastroenteritis, and keratitis occurred in 0.7%-1.8% (moderate to high certainty evidence). Severe pain, abscess, tonsillitis, conjunctivitis, and cellulitis occurred in 2.2%-3.7% of patients (moderate certainty evidence) and hospitalization occurred in 4.4% (low certainty evidence). Patients who were vaccinated had a lower hospitalization rate than those who were unvaccinated. Patients in low- and middle-income countries (LMICs) had a higher rate of pneumonia (2.21% versus 0.02%) than those in high-income countries (HICs). In patients with severe mpox, complication rates were substantially higher. All-cause mortality, abscess, sepsis, tonsillitis, keratitis, and mechanical ventilation occurred in 2.5%-5.5% of patients (moderate certainty evidence). Acute kidney injury, pleural effusion, respiratory failure, and conjunctivitis occurred in 1.4%-2.0% (moderate to high certainty evidence). Patients with severe mpox in LMICs had a higher mortality (3.18% versus <0.01%) than those in HICs. Interpretation:Non-severe mpox is associated with low complication rates and very low mortality, while severe disease carries substantial risks of life-threatening complications and death. These findings provide baseline risk estimates for both patients with severe and non-severe mpox, emphasize the importance of early risk stratification in clinical management, and highlight the need for tailored approaches based on disease severity. The data also reveal health inequities in mpox care between HICs and LMICs, underscoring the urgent need for increased resources in LMICs. Funding:World Health Organization.

Importance How often effect modification analyses in individual participant data meta-analyses (IPDMAs) are prespecified and consistently reported in protocols and corresponding reports remains unclear. Objective To investigate the planning of effect modification analyses in IPDMA protocols and evaluate their concordance with corresponding published reports. Evidence Review In this systematic review, Medline, Embase, the Cochrane Database of Systematic Reviews, and PROSPERO were searched for protocols of IPDMAs of randomized clinical trials from database inception until December 31, 2021, and their corresponding published study reports until January 31, 2024. Paired reviewers independently identified eligible protocols and reports and extracted data. Planning and reporting characteristics of effect modification analyses were summarized, and matched protocol-report pairs were compared for concordance in prespecification of effect modification analyses. Findings Of 356 protocols, 336 (94.4%) had planned effect modification analyses (median, 6 [IQR, 4-10] per protocol). Of those, 12 (3.6%) stated an anticipated direction, 176 (52.4%) planned interaction tests, and 37 (11.0%) planned within-trial analyses. Of 265 protocols using continuous variables as effect modifiers, 15 (5.7%) planned to treat all continuous variables as continuous and 72 (27.2%) planned to categorize all variables without providing justification thresholds. Of 166 identified reports, 149 (89.8%) reported effect modification analyses (median, 7 [IQR, 3-9] per study report). Among those 149 reports, 84 (56.4%) reported prespecified effect modification analyses, 125 (83.9%) reported interaction tests, and 3 (2.0%) stated anticipated effect directions. Among 133 reports using continuous variables, 87 (65.4%) used specified thresholds without providing justification for chosen cut points. Among 166 report-protocol pairs, 32 (19.3%) showed agreement on the number and factors of effect modification analyses. Of 124 mismatched pairs, 95 (76.6%) omitted 1 or more planned effect modification analyses in reports (74 [59.7%] without explanation), and 74 (59.7%) added unplanned effect modification analyses. Among 156 comparable pairs, 15 reports (9.6%) claimed prespecification for effect modification analyses absent from protocols and 84 reports (53.8%) failed to claim prespecification for effect modification analyses prespecified in protocols. Conclusions and Relevance In this systematic review of IPDMAs, protocols and reports often failed to prespecify anticipated effect modification directions, distinguish within-trial from between-trial analyses, and appropriately handle continuous variables. Concordance between protocols and reports was poor, with frequent omission of planned and addition of unplanned effect modification analyses.

BACKGROUND:Triple-negative breast cancer (TNBC), an aggressive subtype lacking oestrogen and progesterone receptors and amplification of HER2 receptors, accounts for 12% to 17% of breast cancers. Adjuvant and neoadjuvant chemotherapy improve survival; however, 30% to 40% of early-stage TNBC cases progress to metastatic disease. Recent evidence suggests that combining immune checkpoint inhibitors (PD-1/PD-L1 inhibitors) with chemotherapy may improve pathological complete response and event-free survival. OBJECTIVES:To assess the benefits and harms of immune checkpoint inhibitors (PD-1 or PD-L1 inhibitors) plus chemotherapy compared with chemotherapy for people with early TNBC. SEARCH METHODS:We searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL, MEDLINE, Embase, the WHO ICTRP, and ClinicalTrials.gov up to 6 November 2024. We also searched the reference lists of identified relevant trials or reviews for potentially eligible studies. SELECTION CRITERIA:Randomised controlled trials (RCTs) comparing PD-1 or PD-L1 inhibitors plus chemotherapy with chemotherapy alone in participants with early TNBC. DATA COLLECTION AND ANALYSIS:Pairs of review authors independently identified studies for inclusion and performed data extraction and risk of bias assessment. Outcomes were pathological complete response, event-free survival (EFS), overall survival (OS), health-related quality of life (HRQoL), and overall rates of any adverse events and serious adverse events (SAEs). We calculated hazard ratios (HRs) for time-to-event data, risk ratios (RRs), odds ratios (ORs), or risk differences (RDs) for dichotomous outcomes, and mean differences (MDs) for continuous outcomes with corresponding 95% confidence intervals (CIs). We performed random-effects meta-analyses to summarise the evidence and evaluated the certainty of evidence using the GRADE approach. MAIN RESULTS:We included seven RCTs with a total of 4341 participants. Two trials investigated PD-1 inhibitors (i.e. pembrolizumab), and five investigated PD-L1 inhibitors (i.e. durvalumab, atezolizumab) in the intervention group. Six studies used neoadjuvant chemotherapy (NACT), and one study used adjuvant chemotherapy (ACT) in the control group. The studies cover a five-year follow-up period. Two studies were at low risk of bias for all reported outcomes. The main limitation of the other trials was lack of blinding. PD-1 or PD-L1 inhibitors plus chemotherapy versus chemotherapy alone beforebreast cancer surgery PD-1 or PD-L1 inhibitors plus chemotherapy probably increase pathological complete response rate (RR 1.47, 95% CI 1.15 to 1.86; 6 studies, 1564 participants; moderate-certainty evidence); improve EFS (HR 0.64, 95% CI 0.52 to 0.79; 4 studies, 1789 participants; high-certainty evidence); and probably improve OS (HR 0.56, 95% CI 0.34 to 0.93; 3 studies, 1681 participants; moderate-certainty evidence) compared with chemotherapy alone. There may be little or no difference between PD-1 or PD-L1 inhibitors plus chemotherapy and chemotherapy alone in HRQoL (MD -1.49, 95% CI -3.88 to 0.91; 2 studies, 1395 participants; low-certainty evidence). PD-1 or PD-L1 inhibitors plus chemotherapy probably have little or no effect on any adverse events (OR 0.26, 95% CI 0.05 to 1.24; 3 studies, 1781 participants; moderate-certainty evidence) and treatment-related deaths (RD 0.2%, 95% CI -0.4% to 0.8%; 4 studies, 1761 participants; moderate-certainty evidence) compared with chemotherapy alone. PD-1 or PD-L1 inhibitors plus chemotherapy probably increase immune-related SAEs (OR 1.75, 95% CI 1.15 to 2.67; 5 studies, 2016 participants; moderate-certainty evidence) compared with chemotherapy alone. PD-1 or PD-L1 inhibitors plus chemotherapy versus chemotherapy alone afterbreast cancer surgery There may be little or no difference between PD-1 or PD-L1 inhibitors plus chemotherapy and chemotherapy alone in EFS (HR 1.11, 95% CI 0.87 to 1.42; 1 study, 2199 participants; low-certainty evidence), OS (HR 1.23, 95% CI 0.87 to 1.73; 1 study, 2199 participants; low-certainty evidence), HRQoL (MD -1.02, 95% CI -2.71 to 0.67; 1 study, 2168 participants; low-certainty evidence), any adverse events (OR 3.38, 95% CI 0.93 to 12.33; 1 study, 2177 participants; low-certainty evidence), and treatment-related deaths (RD -0.1%, 95% CI -0.4% to 0.2%; 1 study, 2177 participants; low-certainty evidence). PD-1 or PD-L1 inhibitors plus chemotherapy probably increase immune-related SAEs (OR 1.81, 95% CI 1.47 to 2.24; 1 study, 2177 participants; moderate-certainty evidence) compared to chemotherapy alone. AUTHORS' CONCLUSIONS:Combining PD-1 or PD-L1 inhibitors with chemotherapy compared to chemotherapy alone before breast cancer surgery improves pathological response, EFS, and OS in early TNBC. In contrast, the combination of PD-1/PD-L1 inhibitors with chemotherapy after breast cancer surgery may have little to no effect on EFS and OS in early-stage TNBC when compared with chemotherapy alone. The addition of PD-1 or PD-L1 inhibitors probably increases immune-related SAEs.

Artificial intelligence (AI) is having a profound impact on the production of medical knowledge, research paradigms, healthcare services and the health industry. Traditional Chinese medicine (TCM), a valuable part of human heritage and an important global health resource, is entering a period of historic innovation through its integration with AI. This convergence offers significant opportunities for the collation of classical literature, the inheritance of clinical experience, diagnosis and treatment, drug discovery, talent cultivation, industrial upgrading and health management. However, AI-enabled TCM is still in its infancy and faces challenges relating to theoretical compatibility, data quality, scientific evaluation, algorithmic transparency, ethical governance, standardization, interdisciplinary training and international coordination. The Hangzhou Declaration on the Global Development of Artificial Intelligence in Traditional Chinese Medicine sets out a shared position and a consensus based on principles for trustworthy innovation in this emerging field. It emphasizes preserving the essence of TCM while pursuing innovation, prioritizing clinical value and patient safety, strengthening ethical governance, improving data standards and scientific evaluation, fostering interdisciplinary collaboration, advancing international standards, bridging the digital divide, and cultivating globally competent talent. The Declaration aims to guide the responsible, open, inclusive and sustainable development of AI-enabled TCM, contributing to the health and well-being of humanity. Please cite this article as: Fan XH, Li Y, Lai XB, Zhang JH, Li HY, Hu KF, Li J, Chen JX, Pan HD, Wen CB, Ye Q, Kan HX, Li XX, Li PF, Hu Y, Chen KX, Zhang BL. Hangzhou declaration on the global development of artificial intelligence in traditional Chinese medicine. J Integr Med. 2026; Epub ahead of print.

BackgroundPharyngitis, a prevalent upper respiratory tract disorder, significantly impairs patients’ health-related quality of life due to persistent symptoms such as sore throat and dryness. In particular, the recurrent and lingering nature of chronic cases places a substantial strain on both the healthcare system and society. Although conventional therapies dominated by anti-infective and anti-inflammatory agents are widely employed, their efficacy in curbing recurrence and enhancing long-term prognosis remains suboptimal. Conversely, Traditional Chinese Medicine (TCM) has demonstrated potential advantages in modulating the local inflammatory microenvironment and regulating systemic function, leading to a rapid proliferation of related randomized controlled trials (RCTs). Nevertheless, existing clinical evidence is plagued by significant heterogeneity in the selection and reporting of outcome measures. A substantial number of studies excessively rely on ill-defined composite endpoints, such as the “total effective rate,” or utilize ad hoc symptom scales lacking validation for reliability and validity, thereby precluding high-quality quantitative assessment. Such non-standardized and fragmented evaluation criteria severely impede cross-study evidence synthesis and comparison, consequently restricting the formulation of high-level evidence-based clinical guidelines.ObjectivesThe primary objective of this protocol is to develop a Core Outcome Set (COS) specifically tailored for clinical trials of Traditional Chinese Medicine (TCM) in the treatment of pharyngitis. This process will strictly adhere to the international standards established by the Core Outcome Measures in Effectiveness Trials (COMET) Initiative, employing a systematic methodological framework that integrates diverse stakeholder perspectives.MethodsThe development process will unfold in four distinct phases. First, a systematic review will be conducted to comprehensively capture all previously reported outcomes in pharyngitis research, thereby establishing an initial item pool. Second, qualitative research comprising semi-structured interviews will be utilized to uncover outcomes deemed critical by patients and frontline clinicians that may have been overlooked in existing literature. Third, a multidisciplinary panel—including TCM and Western medicine practitioners, pharmacologists, methodologists, and patient representatives—will participate in a two-round Delphi survey to anonymously rate the importance of these outcomes. Finally, a face-to-face consensus meeting employing the modified Nominal Group Technique (NGT) will be convened to vote on and ratify the final COS items, along with their definitions and recommended measurement instruments.DiscussionThe establishment of this COS is expected to standardize outcome reporting in clinical trials regarding TCM for pharyngitis. By mitigating selective reporting bias and facilitating evidence synthesis, this COS will support high-quality guideline development, ultimately enhancing both research integrity and the standard of patient care.Clinical trial registrationhttps://www.comet-initiative.org/Studies/Details/2601, identifier 2601.

PurposeConsiderable variability exists in the outcomes reported in trials of traditional Chinese medicine (TCM) for acute pharyngitis, limiting the comparability and applicability of findings. This review aimed to systematically examine outcome selection, measurement, and reporting in these studies to inform the development of a core outcome set (COS).MethodsA systematic search was conducted to identify randomized controlled trials evaluating TCM interventions for acute pharyngitis. Data on study characteristics, outcome domains, specific outcomes, measurement instruments, and assessment time points were extracted. Outcomes were categorized using an established outcome taxonomy, and a narrative synthesis was performed to evaluate patterns of outcome reporting.ResultsA total of 182 studies were included. Six broad outcome domains comprising 817 individual outcomes were identified. Substantial heterogeneity was observed in outcome selection, definitions, and measurement approaches, with most outcomes reported in only a small proportion of studies. Symptom- and sign-based outcomes were universally reported, whereas domains such as quality of life, economic evaluation, and long-term prognosis were rarely addressed. Standardized patient-reported measures and validated instruments were infrequently used. In addition, outcome reporting was often limited to short-term clinical effects, with minimal integration of safety, patient-centered, or health system–level outcomes.ConclusionSubstantial heterogeneity in outcome reporting across TCM trials for acute pharyngitis hinders cross-study comparison and evidence synthesis. This review provides an evidence base for developing a Core Outcome Set (COS) to standardize future outcome assessments and improve trial transparency.

BACKGROUND:The comparative efficacy and safety of high-dose inactivated influenza vaccine (HD-IIV) versus standard-dose inactivated influenza vaccine (SD-IIV) in adults 65 years or older remain uncertain. Hence, we aimed to compare the effects of HD-IIV versus those of SD-IIV for hospitalisation and mortality outcomes in this population by synthesising evidence from randomised controlled trials (RCTs). METHODS:In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Global Health, and ClinicalTrials.gov from inception to Sept 3, 2025, for randomised trials comparing HD-IIV (60 μg of haemagglutinin per strain) with SD-IIV (15 μg of haemagglutinin per strain) in adults aged 65 years or older. We excluded trials of adjuvanted or recombinant vaccines and those conducted during the 2009-10 H1N1 pandemic because the antigenic profile differed from seasonal strains. Pairs of reviewers independently screened studies and extracted aggregate data from eligible reports. Prespecified primary outcomes were hospitalisation for influenza or pneumonia, hospitalisation for influenza, hospitalisation for pneumonia, hospitalisation for laboratory-confirmed influenza, hospitalisation for cardiorespiratory disease, all-cause hospitalisation, and all-cause mortality; serious adverse events (SAEs) were the secondary outcome. We did random-effects meta-analyses and used risk ratio (RR) estimates and baseline risks to calculate absolute risk differences (ie, the difference in absolute number of events per 10 000 vaccinated individuals between SD-IIV and HD-IIV groups) for each outcome. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation framework. The protocol was registered with the OSF Registry. FINDINGS:A total of 1422 records were identified. After screening 813 titles and abstracts, from which 84 full texts were assessed for eligibility, 14 unique RCTs with 581 845 participants were eligible and included in the analyses. Of the 49 outcome results assessed, 32 were rated as low risk of bias and 17 as having some concerns. Compared with SD-IIV, HD-IIV reduced hospitalisation for influenza (RR 0·61 [95% CI 0·50-0·74]; I2=0%; absolute risk difference -4 events per 10 000 vaccinated individuals [95% CI -5 to -3]; high certainty), hospitalisation for laboratory-confirmed influenza (RR 0·68 [0·58-0·80]; I2=0%; absolute risk difference -4 events per 10 000 vaccinated individuals [-5 to -3]; high certainty), hospitalisation for cardiorespiratory disease (RR 0·92 [0·86-0·98]; I2=5·9%; absolute risk difference -15 events per 10 000 vaccinated individuals [-26 to -4]; high certainty), and all-cause hospitalisation (RR 0·97 [0·95-0·99]; I2=8·7%; absolute risk difference -29 events per 10 000 vaccinated individuals [-48 to -10]; high certainty). There was probably little or no difference between the effects of HD-IIV and SD-IIV on all-cause mortality (RR 0·98 [0·92-1·05]; I2=0·0%; absolute risk difference -1 event per 10 000 vaccinated individuals [-4 to 3]; moderate certainty). Compared with SD-IIV, HD-IIV might have little or no effect on hospitalisation for influenza or pneumonia (RR 0·83 [0·66-1·03]; I2=71·3%; absolute risk difference -7 events per 10 000 vaccinated individuals [-14 to 1]; low certainty), hospitalisation for pneumonia (RR 0·85 [0·66-1·08]; I2=72·0%; absolute risk difference -9 events per 10 000 vaccinated individuals [-21 to 5]; low certainty), or SAEs (RR 0·97 [0·93-1·01]; I2=16·4%; absolute risk difference -18 events per 10 000 vaccinated individuals [-41 to 6]; low certainty). INTERPRETATION:HD-IIV could be considered as a strategy to reduce hospitalisation burden in adults 65 years or older; however, the evidence does not support routine preferential use across all older adults irrespective of context. Absolute benefits were modest on average, and the value of HD-IIV is likely to depend on baseline risk, health-care context, and implementation considerations. FUNDING:National Natural Science Foundation of China Youth Science Fund and Shandong Provincial Natural Science Foundation Youth Science Fund.

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.

OBJECTIVE:To develop a core outcome set (COS) for clinical trials on post COVID-19 condition (PCC), that is, what, when, and how to measure PCC. METHOD:A comprehensive collection of outcomes (including their measurement methods and phases) was launched via literature review and clinician and patient surveys. Two rounds of Delphi surveys were conducted under the predefined criteria for rating, followed by a consensus meeting to finalize the COS for PCC (COS-PCC). RESULTS:Fifty-two outcomes within 7 categories and 206 measurement methods were identified. Sixty participants from five stakeholder groups completed the first round of the Delphi survey and 41 the second. Consensus was reached among 36 representatives on four domains of respiratory, physical, neuropsychological, and health conditions, including nine core outcomes and their respective measurement methods of priority: dyspnea (modified Medical Research Council scale), cough (Leicester Cough Questionnaire), exercise capacity (6-min walk test), fatigue (Fatigue Severity Scale), pain (Numerical Rating Scale), sleeping disturbance (Pittsburgh Sleep Quality Index), anxiety (Generalized Anxiety Disorder Scale-7), depression (Patient Health Questionnaire-9), and health status (36-item Short Form Health Survey); 16 optional measurement methods achieved consensus for supplement. Measuring phases of each core outcome were prioritized by importance through short and long terms of PCC. CONCLUSIONS:The COS-PCC highlights the key PCC concerns and provides an essential outcome set for PCC assessment in clinical trials and evidence synthesis. With improving the understanding of PCC and accumulating research evidence, the COS-PCC needs to be continuously updated and improved in practice.

The NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome is an intracellular protein complex containing a nucleotide-binding oligomerization domain, leucine-rich repeats, and a pyrin domain. It is a key regulator of inflammation in viral pneumonia (VP). Small-molecule inhibitors targeting various NLRP3 binding sites are advancing into early clinical trials, but their therapeutic utility is incompletely established. Xuanfei Baidu Formula (XF), clinically used for VP treatment, attenuates NLRP3 activation by hampering caspase-11 to impede polarization of pro-inflammatory macrophages in a model of lipopolysaccharide (LPS)-induced lung injury inmice. Herein, we demonstrate that XF attenuated influenza A virus (IAV)-induced lung inflammation as well as lung injury in immunocompetent (but not in macrophage-depleted) mice. RNA sequencing of sorted lung macrophages from IAV-infected mice revealed that XF inhibited activation of the NLRP3 inflammation and interleukin (IL)-1β production. Quantitative nuclear magnetic resonance of XF enabled us to develop XF-Comb1, a fixed-ratio combination of five bioactive compounds that recapitulated the bioactivity of XF in suppressing NLRP3 activation in macrophages in vitro and in vivo. Interestingly, XF-Comb1 inhibited assembly of the NLRP3 inflammasome through multi-site interactions with functional residues of NLRP3, apoptosis-associated speck-like protein containing caspase recruitment domain (ASC), and caspase-1. Taken together, this work advances the development of NLRP3 inhibitors by translating a complex herbal formula into defined bioactive compounds.