Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca²⁺, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.

OBJECTIVE To investigate the prevalence and influencing factors of potentially inappropriate medication （PIM） among the elderly in nursing homes in Urumqi based on three PIM screening tools， and to compare the applicability of different tools. METHODS A cross-sectional study design was adopted. Elderly individuals from six nursing homes in Urumqi were selected as the research subjects from May 2021 to September 2023. Demographic characteristics， disease burden and medication records of the elderly were collected. PIM screening was performed using the Chinese PIM criteria （2024 edition）， the American Geriatrics Society （AGS） Beers criteria （2023 edition）， and the Screening Tool of Older Person’S Prescriptions（STOPP）/Screening Tool to Alert to Right Treatment（START） （2023 edition）. Fleiss’s Kappa test was used to assess the consistency among the three screening tools， and multivariate Logistic regression was used to analyze the influencing factors of PIM. RESULTS The prevalence of PIM screened by the Chinese PIM criteria was 47.4% （323/682）， by the AGS Beers criteria was 43.4% （296/682）， and by the STOPP criteria was 50.9% （347/682）. The consistency among the three screening tools was low （Fleiss’s Kappa＝0.12， P ＜0.001）. Multivariate Logistic regression analysis showed that all three screening tools indicated that polypharmacy， aspirin use and psychotropic drug use were independent risk factors for PIM among elderly in nursing houses （all OR＞1， P ＜0.05）. CONCLUSIONS The prevalence of PIM among the elderly in nursing homes in Urumqi is relatively high. Polypharmacy， aspirin use and psychotropic drug use are common independent risk factors for PIM. There are differences in screening results among the three tools with low consistency. The Chinese PIM criteria can serve as a first-line tool for PIM screening in nursing homes.

Objective:To explore the association between the use of tetracyclines during pregnancy and congenital malformations, with the aim of providing evidence-based guidance for the rational use of antibiotics during pregnancy.Methods:Data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Canada Vigilance Adverse Reaction (CVAR) database from January 2015 to September 2024 were collected. Five methods including Tree-based scan statistic (TreeScan), proportional reporting ratio (PRR), reporting odds ratio (ROR), the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard, and the Bayesian confidence propagation neural network (BCPNN) were used to detect signals of risk for congenital malformations in offspring following maternal use of tetracyclines during pregnancy. A signal that met the threshold criteria of all above 5 methods was considered as a risk signal. Based on population-based cohort of the drug exposures and adverse pregnancy outcomes (DEEP) data from January 2013 to December 2021 in Xiamen City, propensity score matching (PSM)-based Poisson regression was applied to evaluate the association between the first-trimester tetracyclines exposure and congenital malformations in offspring. Adjusted relative risk (a RR) and its 95% confidence interval ( CI) were calculated. Sensitivity analysis was conducted to validate the reliability of the results. Results:A total of 304 098 reports of adverse events during pregnancy were obtained from the FAERS and CVAR databases. Among them, 5 028 reports were related to tetracyclines, including 1 026 reports of congenital malformations in offspring, involving congenital malformations of musculoskeletal system, other digestive system, and other congenital malformations. Signal detection results suggested that tetracyclines may be a risk signal for above congenital malformations in offspring. The DEEP data included 411 936 pregnant women. After PSM, 240 pregnant women exposed to tetracyclines were included. The results showed no significant association between the first-trimester tetracyclines exposure and congenital malformations in offspring (a RR=0.75, 95% CI: 0.26-2.17), sensitivity analysis also showed no correlation. Conclusions:Data mining from the FAERS and CVAR databases suggests a potential association between tetracyclines use during pregnancy and congenital malformations in offspring. However, the DEEP data study shows no significant correlation.

Objective:To test the validity and reliability of the Chinese version of the Peer Mental Health Stig-matization Scale-Revised(PMHSS-R)in middle school students.Methods:A total of 1 099 middle school students were selected and randomly divided into Sample 1(n=549)and Sample 2(n=550)for exploratory factor analysis and confirmatory factor analysis,respectively.The total sample(n=1 099)was used to measure internal consisten-cy,and 87 of them were retested two weeks later.A total of 259 middle school students(Sample 3)was selected for the criterion validity test with the Depression Stigma Scale(DSS)and the Attitudes toward Seeking Professional Psychological Help Scale-Short Form(ATSPPH-SF).Results:Exploratory factor analysis identified 2 common fac-tors,namely stigma awareness and stigma agreement,with a cumulative variance contribution rate of 66.86％.The confirmatory factor analysis showed that the two-factor structure model fit was adequate(x2/df=3.70,CFI=0.97,TLI=0.96,SRMR=0.03,RMSEA=0.07).The PMHSS-R Chinese version scores were positively correlated with the DDS scores(ICC=0.58,P＜0.01)and negatively correlated with the ATSPPH-SF scores(ICC=-0.40,P＜0.01).The Cronbach α coefficients of the total scores and the two-factor scores were 0.90,0.92,0.85,respective-ly.The test-retest reliability coefficients(ICC)were 0.84,0.76,0.78,respectively.Conclusion:The Chinese ver-sion of the Peer Mental Health Stigmatization Scale-Revised(PMHSS-R)demonstrates good validity and reliability in assessing mental health stigma among middle school students.

Objective:To investigate the diversity, temporal dynamics and influencing factors of serotypes of Salmonella among asymptomatic workers in Yulin, Guangxi Zhuang Autonomous Region, from 2013 to 2023, and provide reference for controlling the hidden transmission of Salmonella and for disease prevention among healthy populations. Methods:Anal rectal swabs were collected from asymptomatic workers in Yulin from 2013 to 2023 for the isolation and identification of Salmonella. The diversity of serotypes of Salmonella was evaluated by using Shannon index, while the isolation rates and composition ratio of different serotypes were compared with χ2 test. Spearman correlation analysis was used to evaluate the correlation of natural and social factors with serotype isolation rates for more than eight years, and stepwise multiple linear regression analysis were used to evaluate the impact of social factors on the serotype isolation rates for more than 8 years. Results:A total of 8 073 strains of Salmonella were isolated from 2013 to 2023, with an overall isolation rate of 18.88‰ During the 11-year period, 135 serotypes of Salmonella were identified, and the serotype diversity increased first and then decreased. The serotype with the highest isolation rate was Salmonella Typhimurium (3.04‰), followed by Salmonella Rissen (1.70‰), Salmonella Corvallis (1.41‰), Salmonella Agona (1.36‰), Salmonella Derby (1.22‰), and Salmonella London (1.02‰), accounting for 51.67% of the total Salmonella serotypes isolated. There was no significant trend in isolation rate of Salmonella over the years ( χ2=0.67, P=0.415); however, season significantly influenced the isolation rate, with lower rate being observed in winter and higher rate in summer ( χ2=615.91, P<0.001). The isolation rate of different serotypes of Salmonella was influenced by social and natural factors, showing a positive correlation with temperature, precipitation, and poultry consumption and production levels. Conclusions:The serotypes of Salmonella carried by asymptomatic workers were complex and diverse in Yulin, Guangxi Zhuang Autonomous Region, from 2013 to 2023, and the isolation rates of multi-serotypes increased from 2013 to 2023. Higher isolation rate was observed in summer and the isolation rate was widely influenced by natural factors such as temperature and precipitation, as well as social factors such as economic conditions. It is necessary to pay attention to the Salmonella serotype carriage in healthy population, and strengthen monitoring of both healthy individuals and pathogenic bacteria.

Objective:To investigate the diversity, temporal dynamics and influencing factors of serotypes of Salmonella among asymptomatic workers in Yulin, Guangxi Zhuang Autonomous Region, from 2013 to 2023, and provide reference for controlling the hidden transmission of Salmonella and for disease prevention among healthy populations. Methods:Anal rectal swabs were collected from asymptomatic workers in Yulin from 2013 to 2023 for the isolation and identification of Salmonella. The diversity of serotypes of Salmonella was evaluated by using Shannon index, while the isolation rates and composition ratio of different serotypes were compared with χ2 test. Spearman correlation analysis was used to evaluate the correlation of natural and social factors with serotype isolation rates for more than eight years, and stepwise multiple linear regression analysis were used to evaluate the impact of social factors on the serotype isolation rates for more than 8 years. Results:A total of 8 073 strains of Salmonella were isolated from 2013 to 2023, with an overall isolation rate of 18.88‰ During the 11-year period, 135 serotypes of Salmonella were identified, and the serotype diversity increased first and then decreased. The serotype with the highest isolation rate was Salmonella Typhimurium (3.04‰), followed by Salmonella Rissen (1.70‰), Salmonella Corvallis (1.41‰), Salmonella Agona (1.36‰), Salmonella Derby (1.22‰), and Salmonella London (1.02‰), accounting for 51.67% of the total Salmonella serotypes isolated. There was no significant trend in isolation rate of Salmonella over the years ( χ2=0.67, P=0.415); however, season significantly influenced the isolation rate, with lower rate being observed in winter and higher rate in summer ( χ2=615.91, P<0.001). The isolation rate of different serotypes of Salmonella was influenced by social and natural factors, showing a positive correlation with temperature, precipitation, and poultry consumption and production levels. Conclusions:The serotypes of Salmonella carried by asymptomatic workers were complex and diverse in Yulin, Guangxi Zhuang Autonomous Region, from 2013 to 2023, and the isolation rates of multi-serotypes increased from 2013 to 2023. Higher isolation rate was observed in summer and the isolation rate was widely influenced by natural factors such as temperature and precipitation, as well as social factors such as economic conditions. It is necessary to pay attention to the Salmonella serotype carriage in healthy population, and strengthen monitoring of both healthy individuals and pathogenic bacteria.

Objective To investigate the feasibility and safety of transoral transgastric natural orifice transluminal endoscopic surgery(TG-NOTES)cholecystectomy in miniature pigs.Methods A total of 11 miniature pigs were selected as the experimental subjects and underwent TG-NOTES cholecystectomy.These pigs were divided into the Group A and Group B according to the surgical procedures.Among them,7 miniature pigs in the Group A underwent endoscopic cholecystectomy without dissecting the gallbladder triangle,while 4 miniature pigs in the Group B underwent endoscopic cholecystectomy after dissecting the gallbladder triangle.The success rate of surgery,the time of each stage of surgery,the incidence of complications,the success rate of cholecystectomy and the survival rate of miniature pigs in the two groups were counted.One miniature pig in the Group A and 4 miniature pigs in the Group B were selected for survival experiments.After surviving for 1 week,they were killed and dissected to observe the healing of incision and incidence of complications.Results The surgical survival rate of experimental animals was 100%,and the success rate of cholecystectomy was 100%.There was no significant difference in the surgical time,time of cut the stomach into the abdomen,time of gallbladder exploration or time of gallbladder removal of miniature pigs between the two groups(P>0.05).The time of ligating gallbladder artery of miniature pigs in the Group B was longer than that in the Group A,and the time of isdating gallbladder was shorter than that in the Group A,with statistically significant differences(P<0.05).There was no significant difference in the average number of complications of miniature pigs between the two groups(P>0.05).The dissection of animals after survival experiments revealed that the incisions healed well without serious complications.Conclusion This study successfully establishes the surgical model of TG-NOTES cholecystectomy,and confirms the safety and feasibility of TG-NOTES cholecystectomy.

Objective To investigate the feasibility and safety of transoral transgastric natural orifice transluminal endoscopic surgery(TG-NOTES)cholecystectomy in miniature pigs.Methods A total of 11 miniature pigs were selected as the experimental subjects and underwent TG-NOTES cholecystectomy.These pigs were divided into the Group A and Group B according to the surgical procedures.Among them,7 miniature pigs in the Group A underwent endoscopic cholecystectomy without dissecting the gallbladder triangle,while 4 miniature pigs in the Group B underwent endoscopic cholecystectomy after dissecting the gallbladder triangle.The success rate of surgery,the time of each stage of surgery,the incidence of complications,the success rate of cholecystectomy and the survival rate of miniature pigs in the two groups were counted.One miniature pig in the Group A and 4 miniature pigs in the Group B were selected for survival experiments.After surviving for 1 week,they were killed and dissected to observe the healing of incision and incidence of complications.Results The surgical survival rate of experimental animals was 100%,and the success rate of cholecystectomy was 100%.There was no significant difference in the surgical time,time of cut the stomach into the abdomen,time of gallbladder exploration or time of gallbladder removal of miniature pigs between the two groups(P>0.05).The time of ligating gallbladder artery of miniature pigs in the Group B was longer than that in the Group A,and the time of isdating gallbladder was shorter than that in the Group A,with statistically significant differences(P<0.05).There was no significant difference in the average number of complications of miniature pigs between the two groups(P>0.05).The dissection of animals after survival experiments revealed that the incisions healed well without serious complications.Conclusion This study successfully establishes the surgical model of TG-NOTES cholecystectomy,and confirms the safety and feasibility of TG-NOTES cholecystectomy.

Objective To observe the effects of different doses remimazolam during induction of anesthesia in elderly patients with coronary heart disease undergoing non-cardiac surgery.Methods A total of 120 elderly patients with non-cardiac surgery for coronary heart disease and received general anesthesia under tracheal intubation at Luoyang Central Hospital Affiliated to Zhengzhou University from October 2023 to October 2024,aged 60-85 years.The patients were divided into 3groups by random number table:group R1,group R2 and group R3,with 40 cases in each group,with anesthesia was induced with intravenous injection of remimazolam of 0.2,0.25,0.3mg/kg,respectively.Before induction(T1),modified observers assessment of alertness/sedation(MOAA/S)score reached to 0 points(T2),15seconds after intubation(T3),mean arterial pressure(MAP),heart rate(HR),cardiac output(CO),stroke volume variation(SVV),systemic vascular resistance(SVR),and regional cerebral oxygen saturation(rScO2)were compared among the three groups,as well as the time to loss of consciousness,use of vasoactive drugs,and the incidence of hiccups and hypoxemia were recorded.Results Compared with the T1,MAP and SVR decreased significantly in all groups at T2,with group R2 and R3 showing lower values than group R1(P＜0.05);at T3,the MAP and HR in group R,was higher than group R2 and group R3 compared with T1,the MAP and HR in group R1 were significantly increased at T3(P＜0.05).There was no significant difference in CO,SVV and rScO2 among three groups at different time(P＞0.05).The time of loss of consciousness reduced with the increase of the dose of remimazolam.The application pro-portion of esmololhydrochloride in group R1 and group R2 was more than group R3 during induction of general anesthesia(P＜0.05).There was no significant difference in incidence of adverse events among three groups(P＞0.05).Conclusion Remimazolam can be used safely and effectively for the induction of general anesthesia in elderly patients with coronary heart disease undergoing non-cardiac surger-y,and doses of 0.3mg/kg is more effective for anesthesia induction.