Objective: To investigate the mechanism of shed syndecan-4 (sSDC4) in temporomandibular joint osteoarthritis (TMJOA) in rats, aiming to provide experimental evidence for its prevention and treatment. Methods: This study was approved by the Institutional Animal Ethics Committee. Twelve 6-week-old female Sprague Dawley (SD) rats were randomly divided into two groups. They received a single intra-articular injection into the bilateral superior cavity of temporomandibular joint, which consisted of either 50 μL of 4 mg/mL monosodium iodoacetate (TMJOA model group) or 50 μL of phosphate-buffered saline (PBS, control group). After 4 weeks, the mandibular condylar cartilage was harvested for hematoxylin & eosin (H&E) staining, Safranin O-fast green (SO) staining, and type II collagen (Col-Ⅱ) immunohistochemical staining to assess the degree of cartilage degeneration. The synovium of the temporomandibular joint was collected for immunohistochemical staining to detect the expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) to evaluate the degree of synovial inflammation. Synovial fluid from the temporomandibular joint cavity was collected to measure sSDC4 levels by enzyme-linked immunosorbent assay (ELISA). In addition, 12 6-week-old female SD rats were randomly divided into a His-SDC4 group and a control group, receiving injections into the bilateral superior cavity of temporomandibular joint of either 100 ng/mL (50 μL) of His-SDC4 protein or 50 μL of PBS once every 3 days for a total of 28 days. The same experimental procedures were performed for H&E staining, SO staining, and immunohistochemical staining (Col-Ⅱ IL-6, TNF-α) to observe condylar cartilage degeneration and detect synovial inflammation. Rat synovial fibroblasts and condylar chondrocytes were cultured in vitro and randomly divided into a His-SDC4-stimulated (10 ng/mL) group and control group. Perform CCK-8 cytotoxicity assays and observe cellular morphology under optical microscopy, the mRNA expression levels of IL-6 and TNF-α were detected by real-time quantitative polymerase chain reaction (RT-qPCR), and the levels of IL-6 and TNF-α in cell culture supernatants were measured by ELISA. Results: Compared with the control group, the TMJOA group showed decreased condylar cartilage thickness, percentage of SO-positive area, and percentage of Col-Ⅱ-positive area (all P<0.001); an increased synovitis score (P<0.001) and increased percentages of IL-6- and TNF-α-positive cells in the synovium (all P<0.001); and a significant increase in sSDC4 levels in the synovial fluid (P=0.011). Following intra-articular injection of His-SDC4, condylar cartilage thickness, percentage of SO-positive area, and percentage of Col-Ⅱ-positive area all decreased (all P<0.001); the synovitis score increased (P=0.006), and the percentages of IL-6- and TNF-α-positive cells in the synovium increased (all P<0.001). In vitro experiments showed that His-SDC4 stimulation significantly upregulated the expression levels of IL-6 and TNF-α in both synovial fibroblasts and condylar chondrocytes (all P<0.01), and the levels of these two cytokines in the culture supernatants also significantly increased (all P<0.01). Conclusion During TMJOA progression, the level of sSDC4 in the synovial fluid is significantly elevated, which can directly stimulate synovial fibroblasts and condylar chondrocytes to secrete more pro-inflammatory cytokines, forming a vicious cycle that accelerates TMJOA progression.

OBJECTIVE To evaluate the efficacy， safety， and cost-effectiveness of brivaracetam （BRV） as adjunctive therapy in patients with drug-resistant focal epilepsy.METHODS PubMed， Embase， Cochrane Library， Web of Science， CNKI， Wanfang， and official health technology assessment （HTA） agency websites were searched from inception to January 31， 2026 for HTA reports， systematic reviews/meta-analyses， and pharmacoeconomic studies on BRV. After literature screening and quality assessment， a descriptive analysis was performed.RESULTS A total of 21 publications were included： 13 systematic reviews/meta-analyses， 7 pharmacoeconomic studies （including one study that simultaneously conducted a systematic review/meta-analysis）， and 2 HTA reports. Regarding efficacy， BRV significantly improved the 50% responder rate [risk ratio （RR）＝1.81] and seizure-freedom rate （RR＝5.89） versus placebo. Among third-generation anti-seizure medications （ASMs）， BRV ranked 1st-2nd for seizure freedom， while its 50% responder rate was at a moderate level. The optimal adult dose for seizure freedom was 100 mg/d. Regarding safety， BRV was well tolerated， overall adverse event rates did not differ from placebo， though withdrawal due to adverse event rates were higher than with placebo. Tolerability ranked 1st-2nd among the third-generation ASMs. Psychiatric/behavioral adverse event rates were lower with BRV （6.4%） than with levetiracetam （14.1%）. Regarding cost-effectiveness， BRV showed pharmacoeconomic advantages in countries with lower drug pricing （Australia， Finland） and only in high-risk subgroups in Japan， but did not show such advantages at current prices in the US or Italy. BRV has been included in China’s national reimbursement drug list in 2025， and the economic conclusions drawn during its initial market launch are outdated and require re-evaluation.CONCLUSIONS BRV has proven efficacy and good safety， especially suitable for patients intolerant to levetiracetam. However， due to pricing and medical insurance policies， the cost-effectiveness of BRV after its inclusion in China’s national reimbursement drug list still needs to be re-evaluated.

Chikungunya fever is spreading continuously worldwide，posing a growing public health challenge alongside other arboviral diseases. This article systematically reviews the epidemiological characteristics of chikungunya fever，analyzes the pandemic potential of Aedes mosquito-borne diseases and discusses integrated prevention and control strategies for China in the context of increasing importation risk，drawing on containment practices from multiple countries and regions.

Objective:To investigate the clinical manifestations and genetic characteristics of a Chinese Han family with Axenfeld-Rieger syndrome (ARS).Methods:A pedigree study was conducted.Three people from a Chinese Han family with ARS who visited Henan Eye Hospital in January 2024 were included, including 1 patient.Clinical data of the proband and her parents were collected.Comprehensive ophthalmic examination and general physical examination were performed on the proband and her parents.Peripheral blood samples were obtained from family members for DNA extraction.Whole exome sequencing was performed on the proband, and the copy number of the ZBED1P1, ENPEP, PITX2, and FAM241A genes in family members were validated using the real-time fluorescent quantitative PCR.Axenfeld-Rieger syndrome, Axenfeld-Rieger Syndrome, and PITX2 were used as keywords to search across databases such as OMIM, ClinVar, PubMed, CNKI, Wanfang, VIP, DECIPHER, and Google Scholar.The clinical manifestations and microdeletion types of different patients in ARS literature related to PITX2 microdeletions in China population were summarized, and the relationship between genotype and clinical phenotype was analyzed.The study followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEEC-2024[34]).All subjects understood the purpose of the study and voluntarily signed the informed consent form. Results:The proband was a 25-year-old female, exhibiting diminutive cornea in both eyes, polycoria, deformation and displacement of pupils, a flat mid-face, maxillary dysplasia, tooth loss, and a protruding umbilicus, among other symptoms.Parents of the proband were phenotypically normal.DNA sequencing identified a 1.06 MB microdeletion on chromosome 4q25 in the proband.Real-time quantitative PCR confirmed that this microdeletion encompassed the PITX2 and ENPEP genes, and it was absent in the proband's parents.The ClinGen CNV pathogenicity scoring indicated that the deletion involving the PITX2 gene represented a novel pathogenic copy number variation (CNV).Five studies related to 4q25 microdeletion in Chinese families with Axenfeld-Rieger syndrome was screened, including 13 patients.Clinical manefestations of the 13 patients included corneal disorders (accounting for 100%), umbilical hernia and dental anomalies (accounting for 92%), irregular intraocular pressure (accounting for 62%), iris atrophy (accounting for 46%), and posterior corneal embryotoxon (accounting for 31%). Conclusions:For this Chinese family diagnosed with ARS, a novel pathogenic 4q25 microdeletion variant encompassing the PITX2 gene was found in the proband, which is associated with characteristic phenotypes including microcornea, congenital iris dysplasia, polycoria, tooth loss, and a protruding umbilicus.

OBJECTIVE To construct an evaluation index system for the core competencies of ethics committee members of drug clinical trial institution,providing a basis for optimizing the training system for committee members,improving the quality of ethical review,and fully safeguarding the safety and rights of subjects.METHODS Using methods such as literature research and expert consultation,a preliminary core competency evaluation index system was constructed.The Delphi method was employed to revise and validate it,ultimately forming an evaluation index system for the core competencies of ethics committee members.Based on this system,a questionnaire survey was conducted among 90 ethics committee members from 29 drug clinical trial institutions nationwide,comparing their importance rating and self-assessment scores of the core competency indexes.RESULTS The evaluation system constructed included 4 primary indicators(ethics and professional knowledge,ethics review ability,communication and expression ability,moral integrity and work style)and 39 secondary indicators(familiarity with the content of clinical trial-related laws and regulations,ability to complete project ethics review and identify ethical defects in research protocols within a short period of time,ability to judge the scientific value of clinical research,etc.).The results of questionnaire survey showed that the interviewed ethics committee members had significant capability gaps in dimensions such as regulatory knowledge,ethical norms,review efficiency,risk judgment,and problem analysis.The differences between the importance rating scores of corresponding secondary indicators and the self-assessment scores were all no less than 0.38.CONCLUSIONS This study has developed a quantifiable and stratified core competency assessment tool for ethics committee members.It can provide a scientific framework for committee member training,qualification certification,and standardized management of ethics committees.

Objective:To analyze the mediating effect of cardiovascular health status (CVH) on the association between educational level and cardiovascular disease (CVD).Methods:The participants were from Shanghai Suburban Adult Cohort and Biobank, and questionnaire survey, physical examination, blood biochemistry were conducted from 2016 to 2020 for baseline information collection, and follow up was conducted until March 31, 2024 based on the medical data, CVD incidence data and death surveillance data at different levels. The associations of educational level, CVH and time to CVD onset of the study population were analyzed using the accelerated failure time model to analyze the mediating effects of CVH, health behaviors, and health factors in the association of educational level and time to CVD onset. The mediating effects of educational level, gender, and age moderated associations were also analyzed.Results:A total of 57 312 participants were included, with 2 780 new cases of CVD during a median follow-up of 6.71 (6.71-6.72) years, and a mean incidence density of 7.77/1 000 person-years (95% CI: 7.48/1 000 person-years -8.06/1 000 person-years). In total, the less educational level and the lower CVH, the higher CVD incidence density ( P<0.05). The results of accelerated failure time models showed that the time ratio for CVD-free survival was 1.15 (95% CI: 1.06-1.24) and 1.33 (95% CI: 1.10-1.60) for moderate and high educational level, respectively. The results of the mediation effect analysis showed that the association between moderate and high educational level and time to CVD onset was 29.60% (20.50%-50.00%) and 36.10% (23.80%-59.00%), 9.97% (5.07%-20.00%) and 13.84% (6.84%-29.00%), 15.24% (9.64%-27.00%) and 17.55% (11.58%-33.00%) of mediators mediated by CVH, health behaviors, health factors, respectively. Among them, there was an exposure-mediated interaction of educational level and a positive moderating effect of age. Conclusion:CVH, health behaviors and health factors had a proportionate mediating effect in the association between educational level and risk of CVD development.

Chikungunya fever is spreading continuously worldwide，posing a growing public health challenge alongside other arboviral diseases. This article systematically reviews the epidemiological characteristics of chikungunya fever，analyzes the pandemic potential of Aedes mosquito-borne diseases and discusses integrated prevention and control strategies for China in the context of increasing importation risk，drawing on containment practices from multiple countries and regions.

Objectives:To develop modified prehospital stroke scales and to evaluate their predictive value for in-hospital acute large vessel occlusion (LVO) stroke.Methods:Patients admitted to Dongtai People's Hospital due to non-stroke-related diseases and activated the in-hospital stroke green channel due to suspected stroke symptoms during hospitalization from January 2015 to December 2022 were included retrospectively. According to the final imaging diagnosis, they were divided into LVO group and non-LVO group. The five prehospital stroke scales included Field Assessment Stroke Triage for Emergency Destination (FAST-ED), Rapid Arterial Occlusion Evaluation (RACE), Los Angeles Motor Scale (LAMS), Cincinnati Prehospital Stroke Severity Scale (CPSSS), and Prehospital Acute Stroke Severity Scale (PASS). Multivariate logistic regression analysis was used to determine independent predictive factors of LVO in patients with in-hospital stroke, and incorporating them into the prehospital stroke scale to develop modified scales. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of the modified scales. Results:A total of 174 patients with in-hospital stroke were enrolled, including 92 males (52.9%), aged 65.7±11.9 years. Fifty-four patients (31.0%) had LVO, and 59 (33.9%) had a surgical history within 3 days before the onset of stroke, mainly cardiopulmonary surgeries. Multivariate logistic regression analysis showed that atrial fibrillation (odds ratio 2.940, 95% confidence interval 1.387-6.230; P=0.005) and recent history of cardiopulmonary surgery (odds ratio 6.861, 95% confidence interval 2.437-11.315; P<0.001) were the independent predictive factors of LVO in patients with in-hospital stroke. According to the β coefficient and ROC curve, they were assigned a score of 1 and included in the prehospital stroke scale. The area under the curve of the modified scale for predicting LVO (mRACE: 0.917; mFAST-ED: 0.865; mPASS: 0.859; mCPSSS: 0.853; mLAMS: 0.907) was significantly higher than the corresponding original scale (RACE: 0.888; FAST-ED: 0.820; PASS: 0.786; CPSSS: 0.810; LAMS: 0.859) (all P<0.05). Conclusion:The modified scales based on the prehospital stroke scales can significantly improve the predictive value of in-hospital acute LVO stroke compared to the original prehospital stroke scales.

With the rapid development of population aging in various countries around the world,the health and elderly care industry has been paid high attention.The standardization of smart health and elderly care technology and services is particularly important.This paper firstly reviewed the policies related to healthy elderly care in China.By analyzing the industrial standards and provincial standards issued,this paper focused on the policies proposed by the Shanghai Municipal Government for the standardization of smart health and elderly care,as well as the researches on the standard system and the construction of standard families.Shanghai group standards in the field of smart health and elderly care were summarized,including the guidelines for the construction of standard systems,elderly care service platforms,community elderly cafeterias,portable health monitoring terminals,indoor sports services,and home-based elderly care safety monitoring.A series of case analyses of the standardized implementation of the above aspects were also provided.Through standardization research and practice in recent years,it has been fully demonstrated that the standard research plays an important leading role in the field of smart health and elderly care.

Objective To investigate the effect of obstructive sleep apnea(OSA)on behavioral problems in children and the association between them.Methods A simple random sampling method was used to select 100 children aged 4 to 12 years for the case group.All of them were diagnosed with OSA through overnight polysomnography at the Sleep Medicine Center,West China Fourth Hospital,Sichuan University between October 2022 and October 2023.An additional 100 children without snoring symptoms and clinically evaluated and confirmed as not having OSA were enrolled as the control group.General demographic data of the participants were collected.The Caregiver Report Form of the Achenbach Child Behavior Checklist(CBCL)was used for behavioral problem assessment,and polysomnography data were collected.The chi-square/t test was used to analyze the inter-group differences in general data,the total score of behavioral problems,and scores for each dimension.Linear regression was performed to analyze the relationship between OSA and the total score for children's behavioral problems and those for the different dimensions.Logistic regression was applied to analyze the relationship between the obstructive apnoea-hypopnea index(OAHI)and behavioral problems in children with OSA.A logistic regression model integrating the OAHI×sex interaction term was constructed to evaluate the moderating effect of sex on the association between OAHI and behavioral problems.Results No significant differences were observed in general demographic data between the case and control groups.The total score for behavioral problems and those for each dimension were higher in the case group than those in the control group,with the total score of the case group being 24.60±1.55 and that of the control group being 8.85±0.75(P<0.001).The results of the linear regression analysis showed a positive association between OSA and both the total score for behavioral problems(b=16.01;95%CI,12.56-19.47)and those for each dimension.The results of the logistic regression analysis showed that,after adjusting for covariates,OAHI was a risk factor for behavioral problems in children with OSA(odds ratio[OR]=1.17;95%CI,1.04-1.31).After stratification by sex and adjustment for covariates,the OR value of the effect of OAHI on behavioral problems was slightly higher in female participants(1.57)than that in male participants(1.21).The interaction effect analysis showed that sex moderated the association between OAHI and behavioral problems(OR=1.64;95%CI,1.02-2.64;P=0.04).Conclusion Children with OSA are prone to developing behavioral problems.OAHI is a risk factor for behavioral problems in children with OSA,with a potentially greater effect observed in girls.