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.

Background and Aims:Perihilar cholangiocarcinoma(pCCA)is associated with poor prognosis.Radical resection remains the mainstay of treatment;however,high recurrence rates and limited overall survival(OS)after surgery.Metabolic syndrome(MetS)has been linked to unfavorable outcomes in various malignancies,but its impact on postoperative outcomes in pCCA is unclear.This study aimed to evaluate the influence of MetS on perioperative and long-term outcomes in patients undergoing radical resection for pCCA.Methods:A retrospective analysis was conducted on 223 patients who underwent radical resection for pCCA at the First Affiliated Hospital of Army Medical University between January 2018 and December 2023.Patients were categorized into a MetS group(n=50)and a non-MetS group(n=173)according to diagnostic criteria.Perioperative complications,overall survival(OS),and recurrence-free survival(RFS)were compared between groups.Prognostic factors were identified using multivariate analysis.Results:No significant differences were observed between the two groups regarding median hospital stay,overall complications,or severe complications(all P＞0.05).The 1-,3-,and 5-year OS rates in the MetS group were 62.3％,22.3％,and 0,respectively,compared with 78.2％,39.5％,and 22.0％in the non-MetS group.Corresponding RFS rates were 46.2％,16.9％,and 0 in the MetS group vs.63.8％,29.6％,and 18.8％in the non-MetS group.Median OS and RFS were significantly shorter in the MetS group than in the non-MetS group(15.0 vs.27.0 months;12.0 vs.21.0 months;P=0.021 and P=0.037,respectively).Multivariate analysis identified MetS and major vascular invasion as independent predictors of OS,while MetS,jaundice,R0 resection,and major vascular invasion were independent predictors of RFS(all P＜0.05).Conclusion:MetS is significantly associated with worse long-term survival and higher recurrence risk after radical resection for pCCA.Incorporating MetS into preoperative assessment and postoperative management strategies may help improve patient outcomes.

Objective:To design a safe and convenient temperature-controlled enema device and to verify its effectiveness in enema operation.Methods:This study was a quasi experimental research. A total of 60 patients who were hospitalized in Jilin Provincial Cancer Hospital from October 2023 to January 2024 were selected as the control group, and 60 patients who underwent enema from February to May 2024 were selected as the experimental group adopting convenience sampling method. The control group used traditional enema operation method, while the experimental group used an integrated temperature controlled enema device for enema operation. The heating time of enema solution, retention time of enema solution in the intestine, patient satisfaction rate, and nursing staff satisfaction rate were compared between the two groups before enema operation.Results:There were 39 males and 21 females in the control group, aged (54.78 ± 10.66) years, and 42 males and18 females in the experimental group, aged (56.15 ± 9.88) years. The warming time of enema fluid in the experimental group was 17.00 (15.25, 18.00) s, which was lower than 55.00 (47.00, 59.75) s in the control group, and the difference was statistically significant ( Z = - 9.47, P<0.01). The intraintestinal retention time of enema fluid in the experimental group was 9.50 (9.00, 10.00) min, which was greater than 7.00 (6.00, 8.75) min in the control group, and the difference was statistically significant ( Z = - 7.93, P<0.01); the satisfaction rate of the experimental group was 96.67% (58/60), which was higher than 73.33% (44/60) in the control group, and the difference was statistically significant ( χ2 = 12.81, P<0.01); the satisfaction rate of the nursing staff in the experimental group was 96.00% (48/50), which was higher than 66.00% (33/50) in the control group, and the difference was statistically significant ( χ2 = 14.62, P<0.01). Conclusions:The integrated temperature-controlled enema device reduces the tediousness of nursing operation. It improves the rate of complete preparation of goods, patient satisfaction and nursing staff satisfaction, thereby ensuring efficacy and patient safety.

OBJECTIVE T o explore the distribution of pathogens and risk factors for hospital-associated infections in the laryngeal cancer patients undergoing tracheotomy so as to provide theoretical bases for reasonable clinical use of antibiotics.METHODS Totally 118 laryngeal cancer and tracheotomy patients who were complicated with infec-tions and treated in otolaryngology head and neck surgery department of The First Medical Center of Chinese PLA General Hospital from Oct.2021 to Oct.2024 were retrospectively assigned as the infection group,meanwhile,the 118 patients who were not complicated with infections were chosen as the no infection group.The distribution and drug susceptibility rates of the pathogens isolated from clinical specimens of the patients with infections were observed,and the risk factors for the hospital-associated infections were explored.RESULTS Totally 168 strains of pathogens were isolated from the 118 patients with infections,107 of which were gram-negative bacteria,51 were gram-positive bacteria,and 10 were fungi.The result of multivariate logistic regression analysis showed that age(OR=2.435,95％CI:1.052 to 5.634),duration of tracheotomy(OR=3.525,95％CI:1.871 to 14.259),length of hospital stay(OR=2.829,95％CI:1.099 to 7.276)and complication with diabetes mellitus(OR=4.807,95％CI:1.704 to 13.557)were the risk factors for the hospital-associated infections in the laryngeal cancer pa-tients undergoing tracheotomy(P＜0.05).CONCLUSIONS The gram-negative bacteria are dominant among the pathogens isolated from the laryngeal cancer and tracheotomy patients with hospital-associated infections.The age,duration of tracheotomy,length of hospital stay and complication with diabetes mellitus are the risk factors for the hospital-associated infections in the laryngeal cancer patients undergoing tracheotomy.It is necessary to formulate the prevention and control measures based on the above factors so as to reduce the incidence of infec-tions.

AIM:To investigate the mechanism by which muscle segment homeobox 2(Msx2)regulates the differentiation of outer enamel epithelial cells in the enamel organ.METHODS:Tissue paraffin sections were prepared and subjected to hematoxylin-eosin(HE)staining to analyze the effect of Msx2 deficiency on the differentiation status of epithelial cells in the enamel organ at the morphological level.At the ultrastructural level,alterations in cell structure were analyzed.The intermediate steps mediating cell differentiation were identified.Transcriptome sequencing analysis was performed to validate the molecular mechanisms underlying the observed phenomena.RESULTS:Msx2 deficiency was innovatively found to induce severe squamous epithelial hyperplasia in outer enamel epithelial cells of enamel organ,accompanied by dynamic restructuring of the cell cytoskeleton and alterations in cell adhesion at the ultrastructure level.As a transcriptional repressor,the loss of Msx2 expression results in significant increases(P＜0.05 or P＜0.01)in the mRNA expression levels of integrin β2(Itgβ2),ItgαM,Itgα4,Rac family small GTPase 2(Rac2),Rac/Cdc42 guanine nucleo-tide exchange factor 6(Arhgef6)and protein tyrosine phosphatase receptor type C(Ptprc).CONCLUSION:Msx2 regu-lates cytoskeleton structure and cell-cell interaction through the Rho GTPases signaling pathway,thereby influencing the differentiation state of outer enamel epithelial cells.This study reveals the mechanism through which Msx2 regulates the differentiation of outer enamel epithelial cells,providing a theoretical foundation for the prevention and treatment of enam-el-related clinical dental diseases.

Objective To explore the factors that influence major adverse cardiovascular events(MACE)in atrial fibrillation(AF)patients undergoing radiofrequency ablation(RFA),as well as to compare the prognosis of patients with advanced AF to that of the general population.Methods We prospectively recruited AF patients who underwent RFA treatment at Peking University Third Hospital between January 2021 and March 2023.General patient data were collected through the hospital's inpatient system,and MACE were tracked through outpatient visits and telephone follow-ups.Patients were categorized into three age groups:Group 1(under 65 years),Group 2(65 to 75 years),and Group 3(over 75 years).In this study,MACE was defined as include cardiovascular death,all-cause death,readmission for heart failure,acute coronary syndrome(ACS),grade 2 or higher bleeding and stroke.Results A total of 431 patients were included in this study,with an average age of(66.17±12.22)years.Among these patients,259 were male(60.09％),and the mean of CHA2DS2-VASc score was(1.79±1.30).The median follow-up period was 16.0(11.3,21.3)months,during which 28(6.50％)patients experienced MACE,with ACS and stroke being the most common events.Variables were selected using LASSO regression,and a LASSO-Cox regression model was constructed.Age(HR 1.06,95％CI 1.02-1.10,P=0.006)and hypertrophic cardiomyopathy(HR 3.70,95％CI 1.27-8.68,P=0.008)were identified as independent predictors of MACE after RFA for AF.Subgroup analysis revealed that patients under 65 had significantly better prognoses compared to older AF patients(P=0.030 compared with group 2;P=0.021 compared with group 3).Conclusions Age and hypertrophic cardiomyopathy are independent risk factors for MACE in AF patients undergoing RFA.The prognosis for younger patients is better than that for older patients,while the prognosis for advanced patients is comparable to that of patients aged 65-75 years.

Objective To understand the nursing practice of prone position ventilation for patients with moderate to severe acute respiratory distress syndrome(ARDS)in intensive care unit(ICU)in Shandong province,so as to provide basis for standardizing the nursing practice process of prone position ventilation and carrying out training for hospitals.Methods A self-made questionnaire was used,and convenience sampling was adopted.From September 15th to November 5th,2023,ICU nurses were selected from various hospital levels in Shandong province to investigate the obstructive factors of prone ventilation implementation,the weak links in nursing practice and status,and the occurrence of complications.Results A total of 1 188 questionnaires were collected,of which 991 were valid.92.8%(920/991)of nurses had performed prone position ventilation.The biggest obstacle to the implementation of prone position ventilation was the complexity of patient treatments and multiple devices involved[74.6%(686/920)].Regarding the status of training,90.5%(897/991)of nurses had received training on prone position ventilation and 77.0%(763/991)of nurses felt that training was needed.As for pre-operation assessment,more than 80.0%of nurses evaluated patients'vital signs,airway and secretions and so on,among which the evaluation awareness of analgesia was the worst[81.6%(751/920)].As for the main points of implementation,only 14.0%(129/920)of nurses chose the opposite side of the most important pipeline as the turning direction;48.6%(447/920)of nurses chose the anti-Trendelenburg position;36.3%(334/920)of nurses chose to ventilate≥12 hours.Facial edema[81.7%(752/920)],skin pressure injury[78.9%(726/920)]and eye complication[75.8%(697/920)]were the top 3 most frequent complications.Conclusions ICU nurses'prone position ventilation practices were generally line with the nursing team standard for prone position of adult mechanically ventilated patients and the best evidence recommendation,and needs to be further standardized in aspects of turning direction,position management,ventilation duration,and enteral nutrition management.It is recommended that nursing managers at all levels of hospitals further improve the quality of nursing practice of prone position ventilation according to relevant evidence-based evidence and the actual situation of hospitals.

Objective:To describe the prevalence of anxiety disorders and its distribution in Inner Mongolia Autonomous Region,and to explore the relevant factors of anxiety disorders.Methods:From June 2019 to Decem-ber 2019,representative multi-stage disproportionate stratified sampling procedure was used to sample in residents aged 18 and over in the Inner Mongolia Autonomous Region.All respondents were face-to-face interviewed by trained interviewers.Composite International Diagnostic Interview-3.0(CIDI-3.0)was used to diagnose anxiety disorders according to the criteria and definition of the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ).Chi-square test and multivariate logistic regression analysis were used for statistical anal-ysis.Results:Totally 12 315 people were interviewed in the survey.The weighted 12-mouth prevalence rate of any anxiety disorder was 4.64％,and the lifetime prevalence rate was 6.25％.The weighted 12-month prevalence rate of anxiety disorders was higher in female than that in male(5.38％vs.3.92％).The rate was higher in rural resi-dents than that in urban residents(5.67％vs.3.95％).The rate was higher in people with chronic diseases than that in people without chronic diseases(6.81％vs.2.29％).Logistic regression analysis showed that unmarried(OR=2.32,95％CI:1.31-4.10),separated/divorced(OR=2.49,95％CI:1.33-4.67),in debt(OR=1.55,95％CI:1.04-2.32),chronic disease(OR=2.22,95％CI:1.39-3.53),family history of anxiety disorders(OR=12.05,95％CI:8.78-16.53),poor sleep(OR=2.64,95％CI:1.97-3.54)were risk factors of occurrence of anxiety disorders,while junior high school(OR=0.65,95％CI:0.44-0.96)was protective factor of anxiety disor-ders.Conclusion:Adults with chronic diseases,poor sleep,unmarried or separated/divorced,family history of anxi-ety disorders,and financial debt are at higher risk groups of anxiety disorder in Inner Mongolia Autonomous Re-gion.

Objective:To describe the prevalence and distributions of mood disorder in Inner Mongolia Au-tonomous Region,and analyze the related risk factors.Methods:The multistage stratified sampling method with un-equal probability was used to select permanent residents aged 18 years and over in Inner Mongolia Autonomous Re-gion.The Composite International Diagnostic Interview 3.0 was used as a diagnostic tool.Mood disorders were di-agnosed according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition(DSM-Ⅳ).Single and multivariate analyses were used to investigate the related factors of mood disorders.Results:Totally,12 315 community residents were interviewed in the survey.The weighted 12-month prevalence and lifetime prevalence of mood disorder were 5.4％and 8.7％,respectively.Weighted 12-month prevalence of depressive disorder was 4.9％,and that of bipolar disorder was 0.3％.Among all subtypes of mood disorder,the 12-month prevalence rate of major depressive disorder(3.1％)was the highest.Multivariate logistic regression analysis showed that female,unmarried,separated or divorced,unemployment,family history,other mental disorders,sleep disorders and chronic diseases(OR=1.56,2.80,2.07,1.42,13.46,7.97,3.23,2.13)were risk factors of mood disorder,while aged 65 years and over(OR=0.44)was protective factor of mood disorders.The lifetime consultation rate in patients with mood disorders was 15.5％,the rate of psychiatric consultation was 3.7％,the rate of medication was 1.8％.Con-clusion:It indicates that female residents and people who are unmarried,separated and divorced,unemployed,with family history,suffering from other mental disorders,suffering from sleep disorders,and suffering from chronic dis-eases may be high risk groups of mood disorders,and the utilization rate of health services is rather low in Inner Mongolia Autonomous Region.

Objective To evaluate the effects of transcatheter aortic valve replacement(TAVR)on left ventricular reverse remodeling(LVRR)and outcomes in patients with mixed aortic valve disease(MAVD)and predominant aortic stenosis(AS).Methods Patients undergoing TAVR at our center between January 2020 and December 2022 were enrolled consecutively.Propensity score matching(PSM)(1∶1 ratio)was used to reduce selection bias.Transthoracic echocardiography(TTE)was used to monitor left ventricular ejection fraction(LVEF)and other structural parameters over time.The study outcome was a composite of cardiovascular death and rehospitalization due to cardiovascular causes.Linear mixed-effects models and logistic regression were utilized for comparing echocardiographic changes across groups and identifying independent risk factors for no-LVRR,respectively.Results After PSM,126 patients were included.MAVD group exhibited larger structural parameters(left ventricular end-systolic/end-diastolic diameter and volume,left ventricular mass index)and a lower left ventricular ejection fraction(LVEF)(all P＜0.05).However,more pronounced improvements in left ventricular structure and hemodynamics were observed during follow-up.Multivariate logistic regression analysis indicated that the left ventricular mass index(LVMI)was an independent predictor of left ventricular reverse remodeling(LVRR)after TAVR,whereas persistent moderate or greater mitral regurgitation(MR)and paravalvular leak(PVL)significantly reduced the incidence of LVRR.During a median follow-up period of 23 months,a total of 31 endpoint events occurred,and there was no statistically significant difference in long-term prognosis between the two groups(Log-rank P=0.330).Conclusions Compared to patients in the AS group,those in the MAVD group exhibited more severe left ventricular remodeling before TAVR.However,more significant LVRR was observed during postoperative follow-up.Additionally,the long-term prognosis was comparable between the two groups.