The hierarchical diagnosis and treatment system's two-way referral mechanism is crucial for optimizing medical resource allocation, with medical consortia significantly enhancing this process. It evaluates the implementation dynamics of two-way referral systems within China's medical consortia from 2019 to 2024, focusing on policy evolution, regional disparities, and stakeholder engagement. Despite a positive overall trend, referral rates remain low, with notable regional and institutional disparities. The implementation outcomes span various dimensions, including referral metrics, specific services, timing, and costs; however, these effects are inconsistent and warrant further investigation. The current evaluation index system is diverse but tends to prioritize quantity over quality. Additionally, awareness and satisfaction levels among medical personnel and patients regarding the two-way referral system are uneven and influenced by multiple factors. Currently, China's two-way referral system faces challenges, including low referral volumes, an inadequate evaluation framework, limited research perspectives, and insufficient motivation for stakeholder participation. Future efforts should focus on strengthening primary care infrastructure, enhancing resource collaboration, advancing health insurance reforms, refining the evaluation system, and fostering synergy between hierarchical diagnosis and treatment, the Healthy China strategy, and referral model innovation to advance the hierarchical diagnosis and treatment system. Recommendations emphasize strengthening primary care capacity, reforming insurance payment models, and leveraging digital health technologies to align with the “Healthy China 2030” strategic goals.

Objective: Integration of traditional Chinese and modern medicine (TCM-MM) aids rehabilitation of muscle strength among ischemic stroke (IS) survivors. However, it faces statistical challenges (e.g., multicollinearity, small sample) in the real-world setting. This study tried to provide an analytical framework for investigating linear causality with a retrospective small-sample case series.

Methods: Original data was sourced from hospital information system and processed by many means. Wilcoxon signed-rank test was utilized to execute a self-controlled before-and-after comparison, before multiple linear regression (MLR) models were established for exploring prognostic factors of muscle strength improvement. Afterward, Bayesian networks (BN), mediation analysis and between-subjects effects tests were undertaken the detection of underlying multicollinearity sources progressively. Both clinical interpretability and model performance, containing R² and mean squared error (MSE), served as the indices for modelling comparison.

Results: Muscle strength was significantly improved among 112 post-IS patients after accepting TCM-MM therapies (p < 0.01). Initially, MLR analysis with 11 explanatory variables (EVs) (MLR_1) revealed a probable multicollinearity-driven bias, resulting in reduced interpretability. Consequently, we traced collinearity among EVs using a BN structure that provided clues to mediating and mutual effects for establishing MLR with interactions embracing 11 EVs (MLR_2). Eventually, MLR_2 demonstrated superior model performance (ΔR² = 0.097, ΔMSE = –0.004), and better clinical interpretability. Whereas, we cannot deny a 1/3 probability of diminished statistical efficacy due to the small sample size.

Conclusion: Our study proposed a practically hybrid approach for exploring linear causality under multicollinearity using real-world small-sample data, which suggested that balancing model performance with clinical interpretability can resolve statistical trade-offs in modelling optimization.

Background: Data from Hospital Information Systems are crucial components of real-world data, but concerns arise regarding the transparency of measurement time-points when directly utilizing for efficacy studies. The objective of the study was to analyze the distribution characteristics of time-points for laboratory test records from HIS.

Method: Medical records before December 31, 2019 from Affiliated Hospital of Shandong University of Traditional Chinese Medicine, for patients primarily diagnosed with coronary heart disease (CHD), or heart failure combined with secondary diagnosis of CHD were retrieved from HIS. Fifteen test groups were extracted. The number of records, average of test times, and distribution characteristics of time points were analyzed.

Results: The renal function tests have the most records, and the blood glucose have the most times. Tests time-points distribution showed concentration in the early stage of hospitalization, with the majority occurring within the first 0–10%. For those measured ≥2 times, their first tests are also centrally distributed in the early stage, while the lasts in all period of hospitalization. Besides, substantial difference is showed in the time span of the first and last test. Abnormal value may be a trigger that promotes more intensive examination, and normal or abnormal status of the first examination is significantly weak to moderate correlated with the number of examinations and time span.

Discussion: The disclosure of time-points of clinical studies based on HIS should be encouraged and the pre-survey of data measuring time point is essential to the design of trial.

Objective: Several studies suggested that the risk of cardiovascular disease (CVD) had increased before individuals developed hyperhomocysteinemia. This study aimed to investigate the dose–response relationship between circulating homocysteine (Hcy) levels and the risk of CVD.

Methods: Observational studies examining the relationship between circulating Hcy levels and CVD risks were included. Searches were conducted on English databases (PubMed, Embase, and Web of Science) and Chinese databases (CNKI, WanFang, VIP, and SinoMed) in May 2025. Combined relative risks (RRs) or odds ratios (ORs) were calculated using random-effects models. The dose–response relationship between circulating Hcy levels and CVD risks was assessed using restricted cubic spline analysis. The risk of bias was assessed using the Newcastle–Ottawa Scale for cohort and case-control studies, and the Agency for Healthcare Research and Quality criteria for cross-sectional studies. Publication bias was assessed using funnel plots and the trim-and-fill method.

Results: A total of 117 original studies (35 cohort studies, 60 case-control studies, and 22 cross-sectional studies) were included, involving 504,469 participants with 43,089 CVD cases. Elevated circulating Hcy levels were significantly associated with increased CVD risks in all study types (RRs/ORs: 1.61–2.14). A non-linear dose–response relationship was observed between circulating Hcy levels and CVD risks (all p < 0.001), with thresholds at 10.4 µmol/L for cohort studies, and 10.0 µmol/L for both case-control studies and cross-sectional studies.

Conclusions: In this meta-analysis, increased Hcy levels were linked to higher CVD risks. Circulating Hcy level >10 µmol/L may implement nutritional intervention in primary prevention of CVD.

Aim: Microsatellite instability (MSI) as a result of deficient deoxyribonucleic acid (DNA) mismatch repair (dMMR) is a key contributor to the development of tumors with a high mutation rate and cancer-specific neoantigens. dMMR identification can be beneficial for selection of immune checkpoint inhibitor (ICI) therapy-eligible patients. While multiple studies have focused on dMMR prevalence in colorectal cancer (CRC), fewer investigate the prevalence of dMMR in tumor types besides CRC, especially in Chinese patients. In this study, we aimed to determine the prevalence of dMMR in China across five gastrointestinal and gynecological tumor types.

Methods: Tissue samples from Chinese patients with advanced endometrial, ovarian, cervical, biliary tract, or gastric metastatic or unresectable solid tumors were tested for dMMR status using immunohistochemistry with the Ventana MMR RxDx panel. Data were analyzed to determine the prevalence of dMMR for each tumor type.

Results: A total of 748 patients were included in the study, representing five tumor types. Prevalence of dMMR varied across tumor types, with an overall prevalence of 9.4%. Patients with endometrial tumors had the highest proportion of patients with dMMR at 49/164 (29.9%). Patients with cervical tumors had the lowest prevalence of dMMR with 6/221 (2.7%) patients. The prevalence of dMMR was similar across most demographic characteristics. In the dMMR population, co-occurring MLH1 and PMS2 protein loss across all tumor types was observed most commonly, in 48/70 (68.6%) patients.

Conclusions: These data highlight the importance of dMMR testing in patients with advanced solid tumors in China to optimize biomarker testing and treatment decisions.

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.

Background: Systematic reviews on acupuncture for obesity report conflicting findings, and the certainty of this evidence remains unclear. This umbrella review appraises the evidence to identify which effects on body mass index (BMI) and body weight (BW) are supported by high-quality findings.

Methods: We conducted an umbrella review by systematically searching PubMed, Embase, and the Cochrane Library through April 28, 2025 to obtain systematic reviews of randomized controlled trials evaluating acupuncture interventions for obesity. Two reviewers independently assessed methodological quality using a measurement tool to assess systematic reviews (AMSTAR) and evidence quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). We identified best evidence from high-quality systematic reviews with high or moderate GRADE ratings.

Results: Our analysis included 22 systematic reviews encompassing 60 meta-analyses. Seventeen reviews (77.3%) achieved high methodological quality ratings according to AMSTAR criteria. Five meta-analyses provided high-quality evidence consistently demonstrating significant benefits of acupuncture interventions. The strongest evidence supported acupuncture combined with lifestyle interventions compared to lifestyle interventions alone for both BMI and BW outcomes. Additional high-quality evidence demonstrated significant benefits for acupuncture versus no treatment and versus sham acupuncture. Fourteen meta-analyses provided moderate-quality evidence confirming acupuncture effectiveness, with no significant differences between acupuncture and pharmaceutical treatments.

Conclusions: Based on high-quality evidence, clinicians can recommend acupuncture to patients with obesity, particularly as adjunctive therapy to lifestyle interventions. For patients unable to tolerate pharmacological treatments, acupuncture represents a reasonable alternative. However, optimal benefits require integration with comprehensive lifestyle modifications rather than standalone use.

Background: Anlotinib, a multi-target small-molecule receptor tyrosine kinase inhibitor, can inhibit tumor angiogenesis proliferation and remains underexplored in metastatic breast cancer (MBC). Therefore, we aimed to analyze the efficacy and safety of anlotinib for MBC treatment in a real-world study.

Methods: In this multicenter, retrospective study, patients with MBC who received anlotinib at four Chinese centers between January 2021 and December 2022 were enrolled (data cut-off date: February 1, 2025). The primary end point was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate, and adverse events (AEs). Statistical significance was defined at p < 0.05.

Results: In total, 153 patients were included in this study (median age, 51 years). Median follow-up time was 30.0 months. A total of 86 (56.2%) patients were hormone receptor-positive/human epidermal growth factor receptor 2-negative, whereas the others were human epidermal growth factor receptor 2-positive (9.8%) or triple-negative breast cancer (34.0%). The median PFS and OS were 6.0 months (95% confidence interval [CI] 4.5–7.5) and 28.5 months (95% CI 20.3–36.7). The number of metastatic sites and Eastern Cooperative Oncology Group performance status were significant in Cox multivariate analysis (p = 0.012 and p = 0.030, respectively) and were significantly associated with PFS of anlotinib. Most AEs were clinically manageable, whereas Grade III/IV AEs included neutropenia (29.4%) and fatigue (6.5%).

Conclusion: Anlotinib exhibits effective and safe anti-tumor activity in the treatment of MBC.

Aim: The quality of drug clinical trials is crucial for authorizing new drugs and fostering innovations in clinical practice. This study aimed to report the status, trends, and factors of the quality of drug clinical trials in China.

Methods: This mixed methods study assessed trial quality using quantitative data from public sources and qualitative data from focus groups and interviews with key stakeholders.

Results: The No Action Indicated findings issued by the Food and Drug Administration increased from 43% from 2009–2015 to 88% from 2016–2022, whereas the Official Action Indicated findings decreased from 9% to 0% (p = 0.001). The Center for Food and Drug Inspection revealed that 12% of new drug applications in 2015–2017 were suspected of data fabrication, compared to only 0.6% failed to pass the inspection in 2022 (p < 0.001). Number of drug trials published by Chinese institutions in top medical journals increased from 1.3% in 2009 to 4.9% in 2022 (p for trend <0.001). Moreover, the number of clinical trial guidelines increased from approximately 10/year from 2015–2019 to 50–60/year from 2020–2022, number of internationally accredited ethics committees increased from 4 in 2009 to 82 in 2022, and over 130,000 individuals received training on the International Council for Harmonization guidelines. Interviews with stakeholders revealed a consensus on quality improvement, attributed to seven key factors, and highlighted further recommendations to enhance clinical trial quality in China.

Conclusions: The quality of drug clinical trials in China has significantly improved over the past decade, yet there remains scope for further enhancement.

Objective: This study aimed to describe the incidence, mortality, and disease burden of tracheal, bronchial, and lung cancer (TBL) in both China and worldwide.

Methods: We extracted estimates of the incidence, mortality, and disability-adjusted life years (DALYs) for TBL from the Global Burden of Disease 2021 database. The age-period-cohort model was employed to explore the impacts of age, period, and birth cohort on TBL. Joinpoint regression analysis examined long-term trends in TBL incidence, mortality, and DALYs. Correlation analysis was conducted to investigate the relationship between TBL disease burden in 2021 and the economic development level of the regions.

Results: In 2021, the global age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR) for TBL were 26 (95% uncertainty intervals [UI]: 24–29), 24 (95% UI: 21–26), and 533 (95% UI: 480–586) per 100,000 population. In all regions, regardless of economic level, male TBL incidence, mortality, and DALYs were significantly higher than those in females. After age 45, the ASIR, ASMR, and ASDR for TBL showed a geometric increase, peaking after age 85. Regions with higher economic levels faced higher TBL incidence and disease burden.

Conclusion: In some less developed regions, the disease burden of TBL has shown an upward trend. The heterogeneous long-term trends observed across different sexes and age groups highlight the need for greater attention to issues such as excessive smoking and environmental exposure among middle-aged and elderly populations, particularly women.

Aim: Hypokalemia is a prevalent complication following pituitary adenoma (PA) surgery, adversely impacting patient prognosis. Identifying predictors of early postoperative hypokalemia is crucial for managing patients effectively. This study aims to develop an interpretable predictive model to predict postoperative hypokalemia in patients with PA and recognizes individualized significant parameters contributing to the predictive outcomes, thereby facilitating early intervention.

Methods: This retrospective cohort study investigated postoperative hypokalemia in 280 patients with PA. We developed a Transformer-based predictive model, CliTab-Transformer, and compared it with an XGBoost-based model and a multilayer perceptron (MLP)-based deep learning model. Model performance was evaluated using metrics such as accuracy, precision, recall, F1 score, and ROC/PR curves, based on five-fold cross-validation. Model interpretability was assessed using a novel Transformer-Explainability method to identify significant parameters contributing to individual predictions.

Results: CliTab-Transformer outperformed XGBoost and MLP in predicting postoperative hypokalemia, showing higher accuracy (0.836 vs. 0.775 vs. 0.771), F1 score (0.845 vs. 0.792 vs. 0.766), sensitivity (0.838 vs. 0.833 vs. 0.771), and AUC (0.835 vs. 0.807 vs. 0.676). The model's interpretability analysis revealed that the preoperative factors, including gender, hypertension, serum potassium concentration, and disease duration, are significantly predictive of postoperative hypokalemia.

Conclusions: Our model outperforms XGBoost in predicting early postoperative hypokalemia in patients with pituitary adenomas. We systematically explore attention mechanisms in clinical tabular data, demonstrating their effectiveness in capturing complex feature interactions, leading to more individualized, interpretable, and clinically meaningful insights.

Background: Percutaneous transhepatic cholangioscopy (PTCS) is a minimally invasive treatment for biliary diseases; however, postoperative biliary drainage can impair quality of life and cause complications. We developed a biodegradable blockage (BB) for tract embolization to replace drainage; this is the first study investigating this approach after PTCS.

Methods: In this prospective study, 10 patients with bile duct stones underwent PTCS with BB embolization (June-August 2024). Outcomes and complications were recorded over 3 months. A 1:1 propensity-matched control group from historical PTCS patients with standard drainage was established for comparison of hemoglobin levels and complications.

Results: BB placement was successful in all patients with no procedure-related deaths. No significant differences were found between the embolization and drainage groups in operative time, hemoglobin changes, or complication rates, though the small sample size warrants caution. One patient in the embolization group had a Grade II complication, versus three complications (two Grade I, one Grade II) in the drainage group. The embolization group had no serious adverse events during follow-up.

Conclusion: Tract embolization with BB appears to be a safe and feasible alternative to conventional drainage after PTCS. Larger randomized trials are needed for validation.

Background and objective: Bailing Capsules (BLC) and Yong Chong Cao Capsules (YChCC) share similar medicinal components, but Yong Chong Cao benefit from more advanced cultivation and large-scale production. This study systematically compared their therapeutic effects in patients with mild-to-severe Chronic Obstructive Pulmonary Disease (COPD).

Patients and method: This study was designed as a multi-center, randomized, active-controlled trial. 240 COPD patients were randomized 1:1 to receive YChCC or BLC for 24 weeks, followed by a 24‑week follow‑up. The primary endpoints were number of acute exacerbations. Secondary outcomes included, time to first exacerbation, and exacerbation duration, forced expiratory volume in 1 s (FEV₁), FEV₁%, forced vital capacity (FVC), FVC%, FEV₁/FVC%, modified Medical Research Council dyspnea scale (mMRC), Chronic Obstructive Pulmonary Disease Assessment Test (CAT), and Chronic Obstructive Pulmonary Disease Clinical Questionnaire (CCQ).

Results: A total of 208 patients completed the trial (full analysis set, FAS), and 178 comprised the per‑protocol set (PPS). Compared with BLC, YChCC significantly reduced the number of acute exacerbations (FAS: p = 0.002; PPS: p = 0.003) and prolonged time to first exacerbation. No significant between‑group differences were observed in lung function parameters or mMRC, CAT, and CCQ scores.

Conclusion: YChCC represent a promising adjuvant therapy for patients with stable COPD, ranging from mild to severe. They significantly prolong the time to the first acute exacerbation and reduce the frequency of acute exacerbations, thereby offering potential benefits in managing COPD.

Trial registration: This trial has been registered at ClinicalTrials.gov under the registration number NCT03745261.

Trial registration number (if clinical trial): NCT0374526

The exponential growth of secondary literature has created an imperative for researchers to identify credible and methodologically sound studies within an increasingly complex information landscape. In light of the growing emphasis on evidence-based medicine in both domestic and international contexts, umbrella reviews (URs) have emerged as a critical methodological approach in biomedical research. As an advanced form of tertiary evidence synthesis, URs systematically integrate findings from multiple systematic reviews and meta-analyses, thereby providing a comprehensive evidence base for specific research questions or related fields. This methodological framework enhances the quality of evidence through critically evaluating the validity and reliability of conclusions drawn from secondary or primary studies. The present overview systematically examines the conceptual framework, distinctive characteristics, development process, and methodological quality assessment of URs, with the objective of establishing a theoretical foundation and practical reference for future research in this domain.

Objective: Upper tract urothelial carcinoma (UTUC) accounts for about 31% of urothelial malignancies in China, a markedly higher proportion than in Western countries. Limited molecular understanding hampers diagnosis and therapy. This study aimed to explore molecular mechanisms and identify potential biomarkers through a cohort-based integrative multi-omics analysis.

Methods: We analyzed 48 paired UTUC tumor and adjacent normal tissues. RNA and whole-exome sequencing were performed to explore difference. Weighted gene co-expression network analysis (WGCNA) was used to identify modules and hub genes associated with pathological traits. Validation included survival analysis within the discovery cohort, cross-cancer evaluation using The Cancer Genome Atlas Bladder Urothelial Carcinoma dataset (TCGA-BLCA) via gene expression profiling interactive analysis, and independent confirmation with a UTUC cohort from cBioPortal (n = 32). Protein expression was examined using immunohistochemistry (IHC) data from the Human Protein Atlas.

Results: We identified 3968 differentially expressed genes enriched in genitourinary development and calcium signaling pathways. WGCNA revealed four co-expression modules associated with infiltration, with 64 genes linked to pathological traits. Integrative analysis prioritized methionine sulfoxide reductase B3 (MSRB3) and Synaptopodin 2 (SYNPO2) as hub genes. Within the UTUC cohort, both genes showed trends toward poorer progression-free survival; in TCGA-BLCA, their expression and survival patterns provided supportive cross-cancer evidence; and in the independent UTUC dataset, clinicopathological correlations were directionally consistent with the discovery findings. IHC suggested lower protein expression in UTUC compared with normal urothelium.

Conclusions: This integrative multi-omics cohort study suggests MSRB3 and SYNPO2 as candidate biomarkers for UTUC progression, offering insights for risk stratification and potential therapeutic development.

Objective: To develop an evidence-based patient version of guideline (PVG) for fibromyalgia, aiming to improve patients’ understanding of disease symptoms and therapeutic options and to enhance their self-management abilities.

Methods: Following the World Health Organization Handbook for Guideline Development (2014), a multidisciplinary working group was established, including patient representatives, physicians, pharmacists, nurses, and methodologists. The process comprised (a) systematic retrieval of clinical practice guidelines and expert consensus statements to establish the evidence base; (b) integration of large language models (LLMs) with expert review to identify and refine key patient-centered concerns; (c) a three-round Delphi consensus guided by the Grading of Recommendations Assessment, Development and Evaluation approach to finalize clinical questions and formulate recommendations; and (d) evaluation of understandability using the Patient Education Materials Assessment Tool for Print Materials (PEMAT-P).

Results: The final PVG covers 13 clinical questions across seven domains, including disease awareness, diagnostic evaluation, pharmacological and non-pharmacological interventions, and long-term management. All recommendations were rated as strong. The guideline emphasizes the importance of pharmacological management, emotional regulation, and exercise in the comprehensive management of fibromyalgia. The PEMAT-P assessment showed an understandability score of 100%.

Conclusions: Developed collaboratively by a multidisciplinary team and patient representatives, this PVG is based on 13 evidence-based fibromyalgia guidelines. Combining LLMs with expert review enhanced question generation and readability. The PVG provides a practical and accessible tool to support early self-management in fibromyalgia.

Aim: To survey the physician's attention to the workload of combining clinical practice with Traditional Chinese Medicine (TCM) data collection.

Background: With the development of artificial intelligence technology in the medical field, the task of collecting diverse clinical data in TCM has increased. Based on the TCM's diagnostic and treatment principles, the collection of research data accompanying clinical practice is inevitable, which may have an impact on TCM clinical practice.

Method: A previous research was conducted to collect diverse instant TCM diagnostic and treatment data, and physicians and research designers proposed many suggestions focusing on the workload of combining clinical practice with TCM data collection. In this study, A 54-item questionnaire was developed based on the suggestions. Forty-eight participants with data-collection experience participated in a questionnaire survey, and they needed to grade each item, which reflected their attention to the workload of combining clinical practice with TCM data collection.

Results: The survey received 40 valid questionnaires, with 49 items scoring 4 or above. Three items in the content dimension (Q9, Q10, Q11) and two items in the spatial dimension (Q31, Q48) are scored lower. Additionally, 25 supplementary suggestions were collected during the study.

Conclusion: The workload of combining clinical practice with TCM data collection needs to be considered. The items in this survey could be regarded as a basis for developing a tool to consider the relationship between clinical practice and data collection.

Objective: To systematically identify immune cell phenotypes causally associated with oral lichen planus (OLP) susceptibility using Mendelian randomization (MR).

Methods: This two-sample MR study evaluated causal relationships between 731 immune cell phenotypes and OLP risk. Single nucleotide polymorphisms (SNPs) were linkage disequilibrium-clumped (r² < 0.001, 10,000 kb), filtered by F-statistic (>10), and harmonized across datasets (palindromic SNPs with intermediate allele frequencies removed). Inverse variance weighting was the primary method, complemented by MR-Egger, weighted median, and mode-based estimations. Heterogeneity (Cochran's Q), horizontal pleiotropy (MR-Egger intercept, MR pleiotropy residual sum, and outlier), and leave-one-out analyses were used for sensitivity checks. Associations passing multiple-testing correction were interpreted.

Results: Twenty-eight immune phenotypes demonstrated significant causal associations: 19 protective and 9 risk-increasing. Five of six regulatory T-cell (Treg) phenotypes showed protective effects, with odds ratios (ORs) ranging from 0.916 to 0.958, and CD3 on CD4 Tregs showing the strongest effect (OR = 0.916). CD8-bright leukocytes showed the strongest risk association (OR = 1.487). Eight B cell phenotypes conferred protection, particularly human leukocyte antigen DR (HLA DR) on B cells (OR = 0.889). Monocyte phenotypes exhibited divergent effects: Myeloid-derived suppressor cells were protective (OR = 0.840), whereas HLA DR-expressing monocytes increased risk (OR range: 1.276–1.281).

Conclusions: This study provides genetic evidence that OLP pathogenesis involves immunoregulatory imbalance between protective regulatory mechanisms and pathogenic effector responses. Findings support precision therapeutic strategies targeting specific immune pathways and offer insights for other oral autoimmune diseases.

Fanconi anemia (FA) is an inherited bone marrow failure syndrome characterized by pancytopenia, cancer predisposition, and physical abnormalities, due to its variable disease manifestations, diagnostic delays are common, making the management of FA is challenging. The core pathophysiology of FA lies in defects in the FA DNA repair pathway, which is crucial for resolving interstrand crosslinks (ICLs) and maintaining genomic stability. Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for FA-associated hematological abnormalities, but its success is influenced by donor type, patient age, conditioning regimens, and graft-versus-host disease (GVHD) management. This review synthesizes current knowledge on FA genetics and pathophysiology, comprehensively analyzes HSCT outcomes in pediatric patients, discusses factors influencing transplant success, and explores emerging therapeutic strategies including gene therapy. By integrating data from large multicenter studies and recent mechanistic insights, this review provides a comprehensive update for clinicians and researchers involved in the care of FA patients.

Case reports represent the earliest form of scientific literature to identify and describe adverse events (AEs) associated with medical interventions, and they still represent important educational resources for ensuring the safe practice of such interventions. Although case reports on AEs related to acupuncture continue to be published, detailed information about the acupuncture procedure is often insufficiently reported in these studies, which may introduce an overstatement or exaggeration of the harm of acupuncture. Consequently, these reports fall short of evaluating causality and achieving the educational purpose of preventing future AEs. To help address these limitations, we developed the “REporting guidelines for aCupuncture-related AdverSe Event case reports” (RECASE) based on the CARE (CAse REports) reporting guidelines for case reports using the expert Delphi methodology. This guideline contains essential items for case reports on acupuncture-related AEs. We anticipate that this reporting guideline will encourage greater transparency, fairness, and comprehensiveness in future case reports on acupuncture-related AEs.

Aim: Infertility is a growing global health issue affecting millions worldwide. While endometriosis, polycystic ovarian syndrome (PCOS) and unexplained infertility are recognized as the major contributors, their specific burden and impact on infertility among women of childbearing age (WCBA) remain inadequately quantified. This study aimed to evaluate the global burden of three diseases and infertility attributable to them.

Methods: Using data from Global Burden of Disease Study 2021, we assessed the temporal trends of three diseases by average annual percentage change (AAPC) in age-standardized prevalence rate (ASPR) and DALYs rate (ASDR), and evaluated their correlation with socio-demographic index (SDI). We also calculated the age-standardized prevalence and years lived with disability (YLDs) rates of infertility attributable to three diseases.

Results: In 2021, the global ASPRs of endometriosis, PCOS, and unexplained infertility were 1070.7 (AAPC: –1.02%, declining), 3364.5 (AAPC: 0.74%, increasing), and 5586.2 (AAPC: 0.70%, increasing), and infertility attributable to three diseases were 60.6, 638.2, and 5586.2 per 100,000 population, respectively. Regionally, Oceania had the highest ASPR for endometriosis, East Asia for unexplained infertility, and high-income Asia Pacific for PCOS. Infertility attributable to PCOS exhibited higher age-standardized prevalence and YLDs rates compared to endometriosis in most regions. Notably, ASPRs and ASDRs for endometriosis and unexplained infertility decreased with SDI, while PCOS rates increased with SDI.

Conclusions: The increasing global burden of endometriosis, PCOS, and unexplained infertility among WCBA has significantly contributed to rising infertility rates, with distinct regional and demographic disparities. Targeted public health strategies are needed to address these trends.