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.

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 analyze the effects of biapenem on the blood concentration of sodium valproate （VPA） in patients with severe infections. METHODS A retrospective collection of patient data was conducted， encompassing individuals admitted to our hospital from January 2021 to May 2024 who were treated with biapenem for severe infections and concurrently or sequentially administered VPA for the prevention or treatment of epilepsy. The effects of various factors on the blood concentration of VPA， including the combination of biapenem， the sequence of biapenem administration， the number of days of biapenem combination， the dosage of biapenem， and the time after biapenem discontinuation. RESULTS A total of 70 patients with 117 VPA blood concentration results were included in this study. When VPA was used alone， no statistically significant difference was observed in the steady-state blood concentrations of VPA between patients who received biapenem first and those who received it later （P＞ 0.05）. There was no statistically significant difference between the steady-state concentration of VPA in patients who received biapenem in combination for 1 to 3 days and those who did not receive the combination therapy （P＞0.05）. The steady-state concentration of VPA in patients not receiving biapenem combination therapy was significantly higher than that of the patients who received combination therapy for 4 to 7 days and more than 7 days （P＜0.001）. With the prolonged duration of combination therapy， the blood concentration of VPA gradually decreased （P＜0.001）. However， no statistically significant difference was observed between the group receiving combination therapy for more than 7 days and the group receiving it for 4 to 7 days （P＞ 0.05）. After 1 to 3 days of combination therapy， no statistically significant differences in VPA blood concentrations were observed among patients with different discontinuation times of biapenem （P＞0.05）. The blood concentration of VPA in patients who received combination therapy for more than 3 days was significantly lower than those who discontinued biapenem 4 to 7 days or more than 7 days after more than 3 days of combination therapy（P＜0.001）. There was no statistically significant difference in VPA blood concentrations between patients receiving a daily biapenem dose ＞1.0 g and those receiving a daily dose ＜1.0 g （P＞0.05）. CONCLUSIONS The concomitant administration of biapenem for 1-3 days has a minimal impact on the blood concentration of VPA. In patients receiving combination therapy for longer than 3 days， VPA blood concentrations return to baseline levels chouxiaoh@163.com within 4-7 days after biapenem discontinuation.

Objective:To analyze the association between remnant cholesterol (RC) and the risk of atherosclerotic cardiovascular disease (ASCVD) in community population in Shanghai.Methods:Using baseline and follow-up data from the Shanghai Suburban Adult Cohort and Biobank, individuals with ASCVD (including coronary heart disease, stroke, myocardial infarction, and peripheral artery disease) at baseline were excluded. A Cox proportional hazards regression model was employed to analyze the relationship between RC and ASCVD risk and the association under different LDL-C levels.Results:A total of 57 281 participants were included, with a median follow-up of 5.61 person-years. During the follow-up, 1 436 ASCVD events (2.51%) were recorded. After adjusting for potential confounders, individuals with moderate ( HR=1.18, 95% CI: 1.03-1.36) or high RC levels ( HR=1.32, 95% CI: 1.15-1.51) had an increased risk of ASCVD. The association was stronger in participants younger than 60 years-old (interaction P=0.048). Participants with RC ≥0.97 mmol/L and LDL-C <3.40 mmol/L demonstrated a 19% ( HR=1.19, 95% CI: 1.06-1.35) increased risk of ASCVD. When RC ≥0.97 mmol/L and LDL-C ≥3.40 mmol/L, ASCVD risk increased by 42% ( HR=1.42, 95% CI: 1.21-1.67). Conclusions:Elevated RC increases ASCVD risk, regardless of LDL-C levels. RC can serve as a valuable predictor and intervention target for ASCVD.

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.

This study started from the connotation of public welfare and, from the perspective of equal rights and responsibilities, interpreted the public welfare responsibilities and entitlements of hospitals. It developed corresponding quantitative measurement tools and constructed a Public Welfare Rights and Responsibilities Index. Public welfare responsibilities were reflected in the provision of equitable, accessible, appropriate, and reasonable basic medical and public health services. These responsibilities were quantified using the market price of basic medical services, the average cost per case-mix index unit, and public service expenditures. Entitlements were reflected in financial subsidies, tax exemptions, and land policy support. Based on this framework, the study applies the Public Welfare Rights and Responsibilities Index to evaluate 147 public hospitals in City S from 2019 to 2021. The results show that the overall level of public welfare among public hospitals in City S was relatively high (with an average index of 2.39), but showed a slight downward trend. Differences were observed across hospital grades and types, with secondary-level hospitals and general hospitals demonstrating relatively higher levels of public welfare. This study could provide a practical and quantifiable method for measuring hospital public welfare within an equal rights and responsibilities framework, offering a novel analytical tool and empirical evidence to support policy formulation and performance evaluation.

Objective To investigate the effects and potential mechanism of tuina on pain and depressive behaviors in rats with neuropathic pain(NP).Methods A total of 102 SD rats were randomly divided into blank group,sham-operation group,model group,tuina group,inhibitor group and inhibitor+tuina group,with 17 rats in each group.The NP model was established by chronic constriction injury of the sciatic nerve.Starting from the 8th day post-operation,the rats underwent a 14-day tuina intervention and stereotactic injection of the SIRT1 inhibitor EX-527(20 μg/μL,0.5 μL)into the hippocampal CA1 region.Pain behaviors were assessed using the mechanical withdrawal threshold test one day before operation and on days 7,14 and 21 post-operation.Depressive behaviors were evaluated using the forced swimming test and sucrose preference test.Nissl staining was employed to observe neuronal morphology and quantity in the hippocampal tissue,while Golgi staining was used to examine dendritic spine density,hippocampal expression of SIRT1/BDNF/TrkB signaling pathway related protein and mRNA were analyzed using immunofluorescence,Western blot and RT-qPCR.Results Compared with the sham-operation group,the model group showed a significant decrease in mechanical withdrawal threshold(P<0.001),prolonged immobility time in the forced swimming test and reduced sucrose preference(P<0.001)on days 7,14 and 21 post-operation;the morphology of hippocampal CA1 neurons was abnormal,with a significant decrease in the number of Nissl positive cells(P<0.001)and a significant decrease in dendritic spine density(P<0.001);the expressions of SIRT1,BDNF and TrkB in dentate gyrus of the hippocampus were significantly reduced(P<0.01,P<0.001),and the protein and mRNA expressions of SIRT1,BDNF and TrkB were significantly reduced(P<0.001).Compared with the model group,the tuina group showed a significant increase in mechanical withdrawal threshold(P<0.01,P<0.001)on days 14 and 21 post-operation,shortened immobility time in the forced swimming test(P<0.01,P<0.001)and increased sucrose preference(P<0.001);the hippocampal CA1 neuronal morphology was improved,with significantly increased Nissl positive cells(P<0.001)and dendritic spine density(P<0.001);the expressions of SIRT1,BDNF and TrkB in dentate gyrus of the hippocampus significantly increased(P<0.01,P<0.001),and the protein and mRNA expressions of SIRT1,BDNF and TrkB were significantly increased(P<0.001).The beneficial effects of tuina were significantly inhibited when the SIRT1 inhibitor EX-527 was used.Conclusion Tuina may alleviate pain and depressive behaviors in NP rats by activating the SIRT1/BDNF/TrkB signaling pathway and improving hippocampal neuronal structural plasticity.

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.

BACKGROUND:For knee osteoarthritis,synovium inflammation and abnormal proliferation and activation of fibroblast-like synoviocytes caused by insuffcient apoptosis are important driving factors for disease progression.Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signaling pathway plays a key role in regulating inflammatory response and apoptosis of synovial cells.As a traditional Mongolian medicine component,Agiophyllum Oligo Saccharides has anti-inflammatory and immunomodulatory functions,but its specific molecular mechanism has not been fully revealed.OBJECTIVE:To explore the effects and mechanism of Agiophyllum Oligo Saccharides on lipopolysaccharide-induced inflammation and apoptosis of mouse synovial cells.METHODS:The mouse synovial cells were randomly divided into a control group,a model group,an Agiophyllum Oligo Saccharides group and a Bay 11-7082 group.Osteoarthritic synoviocyte model was prepared using 1.0 μg/mL lipopolysaccharide intervention for 36 hour.The Agiophyllum Oligo Saccharides group was treated with 1.0 μg/mL lipopolysaccharide and 32 μg/mL Agiophyllum Oligo Saccharides for 36 hours;and the Bay 11-7082 group was firstly incubated for 4 hours with 1 μmol/L NF-κB pathway inhibitor Bay 11-7082,and then 1.0 μg/mL lipopolysaccharide and 32 μg/mL Agiophyllum Oligo Saccharides for 36 hours.Western blot was used to detect TLR4,MyD88,NF-κBp65,p-NF-κBp65,and IκBα protein expression.The level of tumor necrosis factor-α and interleukin-1β in the supernatant were analyzed by ELISA.To detect the expressions of Bax and Bcl-2,western blot and immunofluorescence analysis were performed.The intracellular reactive oxygen species level was detected by DCFH-DA.RESULTS AND CONCLUSION:(1)Compared with the control group,the levels of tumor necrosis factor-α,interleukin-1β and reactive oxygen species,the protein expressions of TLR4,MyD88,Bcl-2,and p-NF-κBp65/NF-κBp65 increased(P<0.05),whereas the protein expressions of IκBα and Bax decreased(P<0.05)in the model group.(2)Compared with the model group,the levels of tumor necrosis factor-α,interleukin-1β and reactive oxygen species,the protein expressions of TLR4,MyD88,Bcl-2,and p-NF-κBp65/NF-κBp65 decreased(P<0.05),while the expressions of IκBα and BAX increased(P<0.05)in the Agiophyllum Oligo Saccharides group.(3)The levels of tumor necrosis factor-α,interleukin-1β and reactive oxygen species and the protein expression of Bcl-2 in the Bay 11-7082 group were higher than those in the Agiophyllum Oligo Saccharides group(P<0.05),but still lower than those in the model group(P<0.05),whereas the expression of Bax protein was lower than that in the Agiophyllum Oligo Saccharides group(P<0.05),but still higher than that in the model group(P<0.05).(4)Compared with the model group and the Agiophyllum Oligo Saccharides group,the protein expressions of TLR4,MyD88 and p-NF-κBp65/NF-κBp65 decreased(P<0.05),whereas the protein expressions of IκBα increased(P<0.05)in the Bay 11-7082 group.To conclude,Agiophyllum Oligo Saccharides could inhibit inflammation of mouse synovial cells and promote apoptosis of synovial cells with inflammation,and the mechanisms may be correlated with regulating the TLR4/NF-κB signaling pathway.