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.

Objective Evidence-based medicine emphasizes clinical research driven by important questions, yet Chinese medicine lacks practical quantitative tools to identify such questions. We developed the Chinese Medicine Interventional Clinical Trials Research Question Importance Tool (CMICT-RQIT) to support topic selection and provide transparent criteria for proposal review, promoting high-quality clinical research in Chinese medicine.Methods This study followed internationally accepted procedures of conceptualization and operationalization. Using a mixed-methods approach-including a literature review, qualitative interviews, Delphi surveys, expert consensus meetings, and the analytic hierarchy process-we developed the CMICT-RQIT. CMICT-RQIT was prespecified and interpreted as a formative/composite multicriteria decision-support tool.Results Following a standardized development process comprising three stages-framework construction, tool development, and tool evaluation-the CMICT-RQIT V1.0 was established. It consists of four domains, 10 facets, and 24 items, each with corresponding composite weights, item explanations, scoring criteria, and an operations manual. Exploratory traditional psychometric analyses showed limited internal consistency and poor structural fit, consistent with the formative/composite nature of the tool and should not be interpreted as evidence that all items measure a single latent trait.Conclusions CMICT-RQIT V1.0 can assist researchers in selecting research topics, with its greatest value lying in providing a concise summary of the importance of research question along with a comprehensive 24-item checklist for clinical investigators. At the same time, it offers reviewers transparent criteria for assessing the importance of research questions, thereby promoting the objectivity and fairness of evaluations. CMICT-RQIT V1.0 should be used primarily as a structured checklist and decision-support index.

BackgroundRheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and joint damage. Despite available treatments, many patients fail to achieve adequate disease control, prompting interest in complementary approaches. In traditional Chinese medicine, multi-herbal formulations such as Formulation C (Qushi-Juanbi Granules) are used clinically to treat RA. Among its component plants, S. costus (S. costus) has long been recognized for its anti-inflammatory properties that have largely been attributed to reactive α-methylene-γ-lactone-containing sesquiterpene lactones. However, comparatively little is known about the activities of non-reactive compounds.ObjectiveThis study aimed to investigate the anti-inflammatory and anti-arthritic potential of S. costus and to determine the contribution of reactive sesquiterpene lactones to this effect.Materials and methodsExtracts from Formulation C plants were screened in cell-based assays targeting RA-relevant pathways (NF-κB, NFAT, STAT3/STAT5), prostanoid formation in a synovial fibroblast cell line, and cytokine production in primary B cells. The aqueous extract of S. costus and an electrophile-depleted version were prepared by elution through thiol-bonded silica and tested in vitro and in the KRN T cell transfer arthritis model in vivo. Seven compounds were isolated from S. costus and their activity characterized in vitro.ResultsScreening identified the aqueous extract of S. costus with potent in vitro activities, mainly affecting the NF-κB and NFAT pathways, and the B cell assay. This activity was lost upon electrophilic-compound depletion, and the sesquiterpene lactones costunolide and dehydrocostus lactone were identified as major active constituents. In vivo, the aqueous extract modestly reduced paw swelling during early disease phase, whereas the electrophile-depleted extract showed minimal activity.ConclusionThis study applies a straightforward thiol-reactive compound depletion method to explore the bioactive constituents of S. costus, a strategy that can be broadly applied to other natural product extracts. Our findings indicate that sesquiterpene lactones are major contributors to the overall anti-inflammatory activity of S. costus, while other, non-thiol-reactive compounds may also play a role for in vivo activity. Overall, these results provide a more detailed characterization of the bioactive profile of S. costus and support its future mechanistic and preclinical investigation for RA research.

Background:Stable angina (SA) remains a major cause of global disability. Xuefu Zhuyu oral liquid (XZOL), a traditional Chinese medicine, is used for SA in China, but rigorous evidence of its efficacy is lacking. We aimed to evaluate the efficacy and safety of XZOL as an adjunctive therapy for patients with SA. Methods:We conducted a multicenter, randomized, double-blind, placebo-controlled trial across six hospitals in China. Between June 2020 and June 2022, eligible patients with SA were randomly assigned (1:1) to receive either XZOL or a matching placebo for 12 weeks, in addition to standard antianginal therapy. All participants were followed for an additional 12 weeks. The primary outcome was the change in average angina pain intensity from baseline to week 12, measured on a 10-cm visual analog scale (VAS). Results:Of 263 patients screened, 148 were included in the full analysis set (74 per group). At week 12, patients receiving XZOL showed a reduction in VAS pain scores compared to placebo (adjusted mean difference, -0.63; 95% CI, -1.12 to -0.14; P = 0.012). This effect was sustained at the 24-week follow-up (-0.47; 95% CI, -0.94 to -0.002; P = 0.049). Furthermore, the XZOL group had significantly lower use of rescue nitroglycerin at both week 12 (2.7% vs. 13.5%; P = 0.016) and week 24 (2.7% vs. 12.2%; P = 0.029). Adverse events were comparable between groups. Conclusion:Adjunctive treatment with XZOL for 12 weeks significantly reduced angina pain intensity and the need for rescue medication in patients with stable angina, with a favorable safety profile. Clinical trial registration:https://clinicaltrials.gov/, ChiCTR1900026899.

Objectives:Primary dysmenorrhea (PD), affecting 50%-90% of women, significantly impacts quality of life. However, the need for treatment remains unmet because of side effects and insufficient efficacy. Xuefu Zhuyu (XFZY) oral liquid is a Chinese patent medicine widely used for PD in China, but high-quality evidence is lacking. Methods:A multicenter double-blind, randomized, placebo-controlled trial was conducted among PD patients aged 18-35 years old. Participants were randomly assigned to receive either XFZY oral liquid or a matched placebo for 3 months. The primary outcome was the change in mean pain intensity as measured by VAS from baseline to the end of treatment. Secondary outcomes included quality of life, the Cox Menstrual Symptom Scale, change of pain duration, painkiller use, etc. Results:Of 256 eligible participants, 129 received XFZY, and 127 received a placebo. There was no significant difference in the primary outcome between groups (adjusted mean difference: -0.18, 95% CI: -0.67 to 0.31, P = 0.463) in FAS analysis. However, the XFZY group had significantly lower rates of painkiller use (9.2% lower during the treatment period, 10.1% lower overall; P < 0.05) and consumed fewer painkillers (P < 0.05) than the placebo group. Other secondary outcomes were not significantly different between the two groups. Adverse event incidence was similar between groups. Conclusions:This trial did not demonstrate a benefit of the change in the mean pain intensity in treating PD with XFZY oral liquid. However, XFZY significantly reduced painkiller use and demonstrated good safety, suggesting its potential as an alternative analgesic for PD. Clinical trial registration:https://www.chictr.org.cn/showproj.html?proj=44287, identifier: ChiCTR1900026819.

BACKGROUND:Oculomotor nerve palsy caused by craniocerebral injury often leads to a significant decline in patients' quality of life. This study aims to explore a comprehensive treatment approach combining Uyghur medicine, rehabilitation training, and acupuncture therapy, and to present a case report evaluating its clinical efficacy in improving ocular motor function and related symptoms. CASE PRESENTATION:A patient sustained craniocerebral injury due to a traffic accident and presented with severe oculomotor nerve palsy. Initial head CT scan revealed multiple intracranial injuries. INTERVENTIONS:The patient received comprehensive treatment consisting of Uyghur medicine guided by differential diagnosis, acupuncture therapy, and structured ocular motor rehabilitation training. The rehabilitation training was administered by a certified rehabilitation therapist with an intermediate professional title and included: eye movement exercises (10-15 times/day), eyelid lifting training (10-20 times/day), visual rehabilitation training (10-15 times/day), and pupillary response training (2-3 times/day), all conducted over a 20-day period. Clinical outcomes, including palpebral fissure height, diplopia score, and pupillary function, were systematically evaluated by the rehabilitation therapist at admission, on day 10, on day 24 (pre-discharge). The overall quality of life of patients was assessed using the 36-item Short Form Health Survey. The study was approved by the institutional ethics committee, and written informed consent was obtained from the patient. RESULTS:Following comprehensive treatment, the patient demonstrated sustained improvement. The 10-day assessment revealed complete resolution of left ptosis and exotropia. Only mild diplopia persisted during esophoria, with moderate improvement in pupillary asymmetry (approximately 1 mm difference). The pre-discharge assessment at 24 days confirmed complete resolution of all primary symptoms (including ptosis, strabismus, and diplopia; diplopia score: 0). Pupil size, shape, and light reflexes returned to normal. No symptom recurrence was observed at the 3-month follow-up; CT imaging demonstrated complete hematoma absorption, fracture healing, and bone remodeling. The patient's 36-item Short Form Health Survey quality of life assessment showed significant improvement across all dimensions. CONCLUSION:This case demonstrates that an integrated treatment approach combining Uyghur medicine, rehabilitation training, and acupuncture yields significant therapeutic efficacy in improving ocular motor dysfunction secondary to complex traumatic brain injury.

BackgroundSarcopenia is recognized as a significant comorbidity in patients with Cardiovascular-Kidney-Metabolic (CKM) Syndrome, yet validated prediction models for this population remain lacking. This study aimed to develop and validate a nomogram for predicting sarcopenia risk in Chinese patients with CKM syndrome.MethodsData were derived from the China Health and Retirement Longitudinal Study (CHARLS) and an independent hospital dataset. The CHARLS 2015 dataset was split into a training set and an internal validation set; the CHARLS 2011 dataset served as the external validation set; and inpatients from Guangdong Provincial Hospital of Chinese Medicine constituted the hospital validation set. Sarcopenia was diagnosed according to the 2025 Asian Working Group for Sarcopenia criteria. Least absolute shrinkage and selection operator (LASSO) regression combined with multivariable logistic regression was used for predictor selection and model development. Model performance was evaluated by discrimination, calibration, and decision curve analysis (DCA).ResultsNine predictors were identified: age, smoking status, high-density lipoprotein cholesterol, triglycerides, uric acid, C-reactive protein, hemoglobin, chronic obstructive pulmonary disease, and chronic liver disease. The model achieved area under the curve values of 0.817, 0.808, 0.800, and 0.834 in the training, internal validation, external validation, and hospital validation sets, respectively. Calibration was satisfactory in development cohorts (p > 0.05), with some calibration drift in external populations. DCA confirmed clinical utility across all datasets.ConclusionThe developed nomogram incorporating nine accessible predictors demonstrated robust discrimination and clinical applicability for sarcopenia risk assessment in Chinese CKM patients, supporting its use in early screening and individualized intervention.

BACKGROUND:Research on blinding and physical consistency between placebo and Chinese medicine is in early stages. We complement novel methodologies for assessing blinding and physical consistency meanwhile investigate different roles of the two evaluations, taking Chinese botanical drug FYTF-919 with matched placebo as an example. METHODS:Subjective evaluation through a clinical trial and objective evaluation by intelligent sensory analysis technology were used in this study. Eligible individuals were recruited and randomly provided FYTF-919 or placebo. Participants were instructed to determine nature of the substance (FYTF-919 or placebo) and compare odor and taste of the given substance with true FYTF-919. Objective evaluation on odor and taste properties was conducted by E-nose and E-tongue. RESULTS:Forty-seven participants completed this trial. More than half participants identified placebo as FYTF-919; comparable proportions of participants in each group identified testing drug as FYTF-919. There's no significant difference in taste score between two groups. Higher odor score for FYTF-919 was associated with medical experience. Consistent with the clinical trial findings, intelligent machines-based sensory evaluation revealed that the two drugs could be confused in taste, whereas their odors were distinguishable. CONCLUSIONS:The placebo was effectively blinded to the traditional Chinese medicine in this study. However, the similarity between the drug and the placebo has not been fully confirmed, as their odor might be detected by the E-nose and medical staff. Therefore, medicine dispensing by dedicated personnel and preventing medical staff from having access to the investigational drugs are necessary for successful blinding throughout the clinical trial. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT05483595.

BACKGROUND:There is an unmet treatment need and a lack of efficacy evidence for Huoxiang Zhengqi (HXZQ) oral liquid for atopic dermatitis (AD). OBJECTIVES:To assess the therapeutic efficacy and safety profile of HXZQ therapy in adult Chinese patients with AD or eczema. METHODS:In the CHARM study (a multi-center, double-blind, randomized controlled trial), randomized participants with mild AD or eczema received HXZQ or a placebo for 4 weeks randomly. The primary outcome was the change in the Eczema Area and Severity Index (EASI) scores from baseline to the end of treatment. Several secondary outcomes were also measured. RESULTS:In total, 218 participants were enrolled who received either HXZQ (n = 110) or a placebo (n = 108). The adjusted difference in the change in the EASI score from baseline to Week 4 between the two groups was -0.44 (95 % confidence interval [CI]:0.83, -0.04; p = 0.033) in the intention-to-treat analysis. At Week 8, 70 participants (66 %) in the HXZQ group had a 50 % or greater reduction from baseline in the EASI score, as compared with 53 participants (50.5 %) in the placebo group (p = 0.022). LIMITATIONS:Only mild AD or eczema participants were observed; due to the limited 4-week treatment timeframe, HXZQ oral liquid's long-term clinical benefits could not be fully determined. CONCLUSIONS:In participants with mild AD/eczema, treatment with HXZQ oral liquid resulted in greater EASI reduction than treatment with placebo at Week 4, and had more benefits in skin clearance benefits over 8 weeks.

Background: Type 2 diabetes mellitus (T2DM) poses a significant global public health burden, where early detection of at-risk populations is imperative for implementing targeted preventive strategies. This systematic review and meta-analysis aimed to evaluate the methodological quality and predictive performance of existing T2DM risk prediction models in screening contexts. Methods: Following the TRIPOD-SRMA statement, eligible studies were selected through searching seven databases (CNKI, WanFang Database, VIP, PubMed, Embase, Web of Science, and the Cochrane Library) from database inception through December 2024. Methodological quality was assessed using the PROBAST tool. Random-effects models synthesized discrimination (AUC). Subgroup analyses explored geographic, modeling, and validation-related heterogeneity. Funnel plots and Egger’s regression test assessed small-study effects. Results: A total of 65 studies (encompassing 97 distinct prediction models) were included in the analysis. Among 97 models, logistic regression dominated (97.9% of models), achieving moderate discrimination (AUC: 0.628–0.916), while machine learning (ML) models showed marginally higher AUCs (up to 0.998). Geographic and cohort disparities emerged, with USA-based models outperforming others (USA AUC: 0.97 vs China AUC: 0.79) and poor performance in prediabetic cohorts (AUC: 0.72 vs 0.80 in normoglycemic). External validation remained limited (21 models), though spatial/temporal validation cohorts demonstrated stable performance. High risk of bias and application (>80% of models) stemmed from inadequate statistical reporting and external verification definitions. Conclusion: ML has favorable diagnostic accuracy for the progression of T2DM. This provides evidence for the development of predictive tools with broader applicability. Future research should prioritize external validation to enhance precision.

OBJECTIVE:This systematic review and meta-analysis seeks to evaluate the efficacy and safety of tip-bendable suction ureteral access sheaths (TBS-UAS) compared to traditional ureteral access sheaths (UAS) in retrograde intrarenal stone surgery (RIRS). METHODS:A thorough literature search was performed across multiple databases, including MEDLINE (via PubMed), Cochrane Library, and Embase (via Ovid) for studies published until January 2025. We included randomized controlled trials (RCTs) and observational studies that reported data on stone-free rates (SFRs), surgical duration, postoperative length of stay, and complication rates. Data were extracted and analyzed using random or fixed effects models to compute pooled relative risks (RRs) and mean differences (MDs), along with their corresponding 95% confidence intervals (CIs). RESULTS:Eight studies involving a total of 1981 patients were included in the analysis. The TBS-UAS group exhibited a statistically significant enhancement in immediate SFR (RR = 1.57, 95% CI: 1.18-2.09) and SFR at 1 month postoperatively (RR = 1.24, 95% CI: 1.05-1.46) compared to the traditional UAS group. Additionally, the TBS-UAS was associated with a lower overall complication rate (RR = 0.41, 95% CI: 0.29-0.56) and a reduced incidence of fever (RR = 0.37, 95% CI: 0.25-0.53). No significant differences were found regarding surgical duration, postoperative length of stay, intraoperative bleeding, or mucosal injury between the two groups. CONCLUSION:The results indicate that the TBS-UAS may provide notable advantages over conventional sheaths in RIRS, particularly in improving SFRs and reducing both overall and infectious complication rates. Further large-scale RCTs are needed to confirm these findings and assess long-term outcomes.

The relationship between gut microbiota, diet, and cardiovascular-kidney-metabolic (CKM) health has attracted attention. However, the relationship between the dietary index for gut microbiota (DI-GM) and CKM syndrome has not yet been studied. Patients diagnosed with CKM syndrome from the NHANES 2007-2018 data were included. Dietary recall data were used to calculate DI-GM. Restricted cubic splines (RCS) were employed to explore nonlinear relationships and determine the threshold for DI-GM. The relationship between DI-GM and CKM syndrome was analyzed using weighted logistic regression. Further, potential mediating roles of phenotype age acceleration (PAA), biological age acceleration (BAA), body mass index (BMI), and body roundness index (BRI) were explored. Sensitivity analysis using inverse probability of treatment weighting (IPTW) was also conducted. A total of 7252 participants were included, with the high DI-GM group as the reference. In the crude model, the risk of CKM syndrome in the low DI-GM group was significantly higher (OR = 1.27, 95% CI = 1.09, 1.49, p < 0.05). This association remained significant in the fully adjusted model (OR = 1.34, 95% CI = 1.10, 1.64, p < 0.05). The results of the IPTW analysis were consistent with the above findings. In the association between DI-GM and CKM syndrome, significant mediating effects were observed for PAA (mediated proportion (MP): 14.84%, p < 0.001), BAA (MP: 21.45%, p < 0.001), BMI (MP: 24.17%, p < 0.001), and BRI (MP: 35.85%, p < 0.001). Low DI-GM is associated with an increased prevalence of CKM syndrome. PAA, BAA, BRI, and BMI significantly mediate the relationship between DI-GM and CKM syndrome.

Background Both preclinical and clinical studies have suggested Huoxiang Zhengqi (HXZQ) oral liquid’s effect on gastrointestinal disease. However, robust evidence in patients with irritable bowel syndrome with diarrhea (IBS-D) is still lacking. Purpose The aim of this study was to assess the efficacy and safety of HXZQ oral liquid for IBS-D patients. Methods This two-arm, multicenter, double-blind randomized controlled trial assessed HXZQ oral liquid’s superiority over a placebo in IBS-D patients. Adults aged 18-70 years with IBS-D from 14 hospitals in China were randomly assigned to receive either HXZQ (20 ml) or a placebo (20 ml), twice a day for 4 weeks. Based on a patient-centered research approach, the primary outcome was binary adequate relief (AR) responder rates. Secondary outcomes were the IBS symptom severity scale (IBS-SSS) score, the IBS quality of life (IBS-QOL) score, and the visual analogue scale (VAS) and utility values on the EuroQol-5-Dimensions-5-Level (EQ-5D-5L). Results 108 of the 212 eligible participants were randomly assigned to the HXZQ group and 104 to the placebo group. At the end of the 4th week, the response rate in the HXZQ group was significantly higher than that in the placebo group, exceeding the efficacy margin of 10% (rate difference: 0.29; 95% CI: 0.14, 0.43). The fragility index (FI) values of AR for the two groups were 13 at 4 weeks and 8 at 8 weeks, respectively. The IBS-SSS score showed a greater reduction in the HXZQ group compared to the placebo group (mean difference: -10.92, 95% CI: -18.93, -2.90). No serious adverse events were reported. Conclusion HXZQ oral liquid may be an alternative option for IBS-D patients in clinical practice.

Background Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that poses a significant socio-economic burden. Traditional Chinese medicine (TCM) herbal formulations, with their long history of clinical use, represent a promising source for novel anti-rheumatic drugs. However, the complexity of RA pathogenesis and the chemical diversity of TCM formulations present challenges in understanding compound-target interactions. Purpose This study aimed to identify the anti-inflammatory constituents from the individual plant species included in the clinically used TCM formulation (“Formulation A”), and to characterize their effects on key inflammatory pathways. Formulation A is currently undergoing a double-blind, randomized clinical trial. A key innovation of this work is the integration of a phenotypic screening strategy, bridging the gap between typical single-species natural product studies and formulation-level decoction studies. Methods A custom panel of phenotypic in vitro assays reflecting key inflammatory pathways relevant to RA (NF-ĸB, NFAT, STAT3, and STAT5) was developed. A suite of plant extracts and fractions was generated, then screened in the above assays. Effects on cytokine production in primary human B cells (IL-6, TNF-α, and GM-CSF) and prostaglandin production (PGD2, PGE2, PGF2α and TxB2) in a fibroblast cell line were also evaluated. Results Plant species within Formulation A displayed a spectrum of biological activities, from minor to broad and more targeted effects. The strongest anti-inflammatory activities were observed in nonpolar extracts and fractions, reflecting the utility of organic solvent extraction for accessing pharmacologically potent constituents that may be underrepresented in traditional water-based decoctions. Two new compounds from Atractylodes lancea were identified, alongside 37 known compounds from other species exhibiting both new and previously known anti-inflammatory activities. These findings also highlight specific molecular effects of the formulation’s components on inflammatory signaling pathways and mediators. Conclusion This study provides mechanistic insights into the anti-inflammatory effects of plant constituents present in Formulation A, based on the systematic analysis of each individual plant species. Moreover, it establishes a robust phenotypic screening platform for the systematic discovery of new anti-rheumatic agents from natural sources.

Background: Stable angina (SA) is a leading cause of disability worldwide, and there is increasing interest in nonpharmacological treatments. Xuefu Zhuyu oral liquid (XZOL) is a Chinese medicine that has been approved in China for the treatment of SA, but further studies are needed to establish its efficacy and safety. We aimed to provide a reliable assessment of the safety and efficacy of XZOL in patients with SA. Methods: We did a multi-centre, randomised, double-blind, placebo-controlled trial at 6 hospitals in China. Participants were randomized into 2 treatment groups, and allocated to receive of either XZOL or matching placebo over 12 weeks and were followed-up for 12 weeks. The primary efficacy outcome was the average pain intensity of angina, which was measured by the change from baseline to week 12 on a 10-cm visual analogue scale. Results: Of 263 patients screened, 148 participants were randomly assigned with primary outcome data in the ITT (intention-to-treat) population (74 in the XZOL group and 74 in the placebo group), and 99 participants in the PP (per-protocol) population (48 in the XZOL group and 51 in the placebo group). Mean change in VAS at week 12 were -2.27 in the XZOL group and -1.85 in the placebo group (difference -0.52, 95% CI -0.99 to -0.05; P = 0.029) among the ITT population, and -2.54 in the XZOL group and -1.79 in the placebo group (difference -0.81, 95% CI -1.40 to -0.22; P = 0.007) among the PP population. The neutral results were shown in adjusted and sensitivity analyses. There was no significant difference in adverse events. Conclusion: This randomised, placebo-controlled, double-blind, clinical trial showed XZOL was associated with a significantly greater reduction in the levels of pain intensity of angina over 12 weeks and was superior to placebo in alleviating SA. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial URL: www.chictr.org.cn ChiCTR1900026899 ### Clinical Protocols ### Funding Statement This work was funded by a grant from the National Key Technology Research and Development Program for the 13th Five-Year Plan of the Ministry of Science and Technology, China (Grant no. 2018YFC1707407). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The protocol was approved by the Ethics Committees at Guangdong Provincial Hospital of Chinese Medicine (No. BF2019-175-01). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The datasets used and analysed in the current study are available from the corresponding author on reasonable request.

BackgroundAngled manual traction (AMT) is widely used for relieving moderate-to-severe cervicobrachial pain in patients with cervical radiculopathy (CR), yet its effectiveness has yet to be established by rigorous full randomized controlled trials (RCTs). We have designed an external pilot to evaluate the feasibility of a future large-scale, definitive RCT on AMT for CR.Methods48 CR participants with cervicobrachial pain (numeric rating scale ≥ 4) will be enrolled in a five-period pilot RCT and randomly assigned to receive either usual care alone or AMT plus usual care for 4 consecutive periods (each period defined as 7 days). The primary outcome will be feasibility, focusing on enrolment rate, retention rate, and protocol adherence. The secondary outcomes include pain in the cervicobrachial region, upper extremity numbness, muscle weakness, upper extremity and neck function, analgesic consumption (non-steroidal anti-inflammatory drugs and opiates), work ability, quality of life, emotional well-being prior to administering treatment at each period’s initial visit, as well as safety and intervention costs during the trial. We employ linear mixed-effect models on the efficacy-related outcome measures to assess the changes within and between groups over time, and determine the statistical trends of effectiveness.ResultsWe expect the trial to be completed by June 2026, with successful pilot targets defined as achieving ≥ 25% enrolment, ≥80% adherence, ≥80% retention, and superior health outcomes in the AMT add-on arm compared with usual care.ConclusionThis external pilot trial will provide robust data on feasibility and outcome variability for power calculations in the proposed future confirmatory RCT on AMT for CR. This pilot RCT will be invaluable to the design and management of the subsequent full-scale RCT.Trial registrationChinese Clinical Trial Registry (ChiCTR): https://www.chictr.org.cn/showproj.html?proj=236348 ChiCTR2400087289.

BACKGROUND:Fuzheng Jiedu granules (FZJD) is widely used for COVID-19 in China, with early studies indicating reduced mortality in severe cases. However, with emerging variants and shifted treatment focus on preventing severity and relieving symptoms, high-level clinical evidence, especially for high-risk patients, remains lacking. METHODS:A randomized controlled trial (ChiCTR2200058181 ) was performed to assess FZJD's efficacy and safety in high-risk adults with non-severe COVID-19. The primary outcome was the proportion of progression to severe COVID-19 after enrollment, with secondary outcomes focusing on the time to resolution of main symptoms. RESULTS:From November 2021 to July 2022, 231 eligible patients were randomized to receive either 15 g of FZJD (n = 119) or placebo (n = 112) thrice daily for 14 days. Patients receiving FZJD (1/101, 1.0 % [95 % CI, 0.0 %, 5.4 %]) had a numerically lower progression proportion to severe COVID-19 than those receiving placebo (2/95, 2.1 % [95 % CI, 0.3 %, 7.4 %]), although with a non-significant difference of -1.1 % (95 % CI, -7.4 %, 6.2 %; p = 0.545) after adjusted by center. FZJD use was associated with significantly shorter time to sustained disappearance of cough (median days, 10.0 vs. 12.0, HR, 1.46 [1.03, 2.07], p = 0.022), fever (median days, 6.0 vs. 7.0, HR, 1.69 [1.03, 2.76], p = 0.031), and chest distress (median days, 7.0 vs. 11.0, HR, 3.28 [1.23, 8.73], p = 0.031). Patients experience comparable adverse events in the two groups (2.7 % in FZJD vs. 1.9 % in placebo). CONCLUSION:Among high-risk COVID-19 patients, FZJD showed obvious symptom improvements and numerically lower disease progression than placebo, without additional adverse events.

Although several studies have suggested that sarcopenia is associated with adverse outcomes in kidney cancer patients undergoing nephrectomy, the results have been inconsistent. Therefore, this meta-analysis was conducted to investigate the relationship between sarcopenia and post-nephrectomy survival in kidney cancer patients. A thorough search was executed across multiple databases, including MEDLINE, Embase, and the Cochrane Library, to identify pertinent studies up to August, 2025. By employing random/fixed effects models, we calculated multivariate-adjusted hazard ratios (HRs) accompanied by their respective 95

This study explored the non-linear relationship between pan-immune inflammation value (PIV) and probable depression using NHANES data (2005-2018, n = 27,049). Restricted cubic spline analysis identified an optimal PIV cutoff (5.74). Weighted logistic regression revealed that individuals with PIV > 5.74 had 14% higher risk of probable depression (OR=1.14, 95% CI:1.02-1.28). Gender-stratified analyses showed significant PIV and probable depression associations in females (OR=1.20, 95% CI:1.03-1.40) but not in males. In males, higher PIV interacted with age, education, and alcohol consumption to influence probable depression risk (interaction P < 0.05), whereas no such interactions occurred in females. The findings suggest PIV may serve as a sex-specific biomarker for probable depression risk, with more stable associations in females. Further research is needed to elucidate the mechanisms underlying these gender differences and validate these findings before any clinical application.