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.

ObjectiveTo investigate the effect of bone morphogenetic protein 3 （BMP3） on the expression of inflammatory factors and joint damage in adjuvant arthritis （AA） induced by Freund′s complete adjuvant （FCA） in rats. MethodsThe AIA model was established in SD rats by intradermal injection of FCA into the toes of the left hind limb， and BMP3 overexpressing adenovirus （Ad-BMP3） or control adenovirus （Ad-NC） was injected in situ into the knee joint cavity on day 8 after modeling. Subsequently， HE staining was used to observe the histopathological changes in the synovium， immunohistochemistry was used to detect the expression of BMP3 in the synovium， and ELISA was used to analyze the expression levels of IL-6， IL-1β and TNF-α in the serum. Primary fibroblast-like synoviocytes （FLS） were isolated from AIA rats， the expression of BMP3 in FLS was knocked down or overexpressed， and Western blot and qRT-PCR were used to detect the expression levels of BMP3 and inflammatory factors in FLS. ResultsHE staining confirmed the successful establishment of the AIA model. Compared with normal rats， AIA rats showed decreased BMP3 expression in synovial tissue. Knockdown of BMP3 promoted the protein expression of inflammatory factors （IL-6， IL-1β， IL-17A， TNF-α） and the mRNA expression of chemokines ［C-C motif chemokine ligand 2 （CCL2）， C-C motif chemokine ligand 3 （CCL3）， Vascular Cell Adhesion Molecule-1 （VCAM-1）］ in FLS. In contrast， overexpression of BMP3 suppressed the expression of these inflammatory factors and chemokines. Intra-articular injection of BMP3-overexpressing adenovirus in AIA rats upregulated BMP3 expression in synovial tissue and inhibited synovial inflammation and bone erosion. ConclusionBMP3 suppresses the production of inflammatory factors and chemokines in FLS， thereby alleviating synovial hyperplasia and bone erosion in arthritis.

In most types of erectile dysfunction, particularly in advanced stages, typical pathological features observed are reduced parenchymal cells coupled with increased tissue fibrosis. However, the current treatment methods have shown limited success in reversing these pathologic changes. Recent research has revealed that changes in autophagy levels, along with alterations in apoptosis and fibrosis-related proteins, are linked to the progression of erectile dysfunction, suggesting a significant association. Autophagy, known to significantly affect cell fate and tissue fibrosis, is currently being explored as a potential treatment modality for erectile dysfunction. However, these present studies are still in their nascent stage, and there are limited experimental data available. This review analyzes erectile dysfunction from a pathological perspective. It provides an in-depth overview of how autophagy is involved in the apoptotic processes of smooth muscle and endothelial cells and its role in the fibrotic processes occurring in the cavernosum. This study aimed to develop a theoretical framework for the potential effectiveness of autophagy in preventing and treating erectile dysfunction, thus encouraging further investigation among researchers in this area.
Male ; Humans ; Autophagy/physiology* ; Apoptosis/physiology* ; Erectile Dysfunction/physiopathology* ; Fibrosis ; Penis/pathology* ; Animals ; Endothelial Cells/pathology* ; Myocytes, Smooth Muscle/pathology*

To investigate the impact of preoperative serum follicle-stimulating hormone (FSH) levels on the probability of testicular sperm retrieval, we conducted a study of nonobstructive azoospermic (NOA) men with different testicular volumes (TVs) who underwent microdissection testicular sperm extraction (micro-TESE). A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital, Shenzhen, China) were retrospectively reviewed. The subjects were divided into four groups based on average TV quartiles. Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups. Overall sperm retrieval rate was 57.6%. FSH levels (median [interquartile range]) were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was <5 ml (first quartile [Q1: TV <3 ml]: 43.32 [17.92] IU l -1 vs 32.95 [18.56] IU l -1 , P = 0.048; second quartile [Q2: 3 ml ≤ TV <5 ml]: 31.31 [15.37] IU l -1 vs 25.59 [18.40] IU l -1 , P = 0.042). Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were <5 ml (adjusted odds ratio [OR]: 1.06 per unit increase; 95% confidence interval [CI]: 1.01-1.11; P = 0.011). In men with TVs ≥5 ml, larger TVs were associated with lower odds of sperm retrieval (adjusted OR: 0.84 per 1 ml increase; 95% CI: 0.71-0.98; P = 0.029). In conclusion, elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs <5 ml. In men with TV ≥5 ml, increases in average TVs were associated with lower odds of sperm retrieval.
Humans ; Male ; Azoospermia/surgery* ; Sperm Retrieval/statistics & numerical data* ; Adult ; Follicle Stimulating Hormone/blood* ; Retrospective Studies ; Testis/pathology* ; Microdissection ; Organ Size

Objective: To explore the effects of Cldn14 gene knockout on renal metabolism and stone formation in rats，so as to provide reference for research in the field of urinary calium metabolism and stone formation. Methods: Cldn14 gene knockout homozygous rats and wild-type rats of the same age were randomly divided into 4 groups：wild-type control (WC) group，wild-type ethylene glycol (WE) group，gene knockout control (KC) group and gene knockout ethylene glycol (KE) group，with 10 rats in each group.The WE and KE groups were induced with ethylene glycol + ammonium chloride to form kidney stones，while the WC and KC groups received normal saline gavage.After 4 weeks of standard maintenance feeding，the urine samples were collected to detect the venous blood.The kidneys were collected for HE，Pizzolatto's staining and transmission electron microscopy.The protein in renal tissues was extracted to detect the expressions of Claudin16 and Claudin19. Results: Crystal deposition was observed in the renal tubular lumen of the WE and the KE groups，and more crystals were detected in the KE group.The WE group had a large number of intracytoplasmic black crystalline inclusions observed in renal tubular epithelial cells under transmission electron microscope，followed by the KE and KC groups.Compared with WC and WE groups，KC and KE groups had significantly decreased serum calcium and magnesium levels but significantly increased urinary calcium level.In addition，the urinary calcium level was higher in the WE group than in the WC group and higher in the KE group than in the KC group.The KE group had lower level of Claudin16，but there was no significant difference in the level of Claudin19 among the 4 groups(P>0.05). Conclusion: Knockout of Cldn14 gene alone cannot effectively reduce urinary calcium excretion or reduce the risk of stone formation in rats，which may be related to the decrease of Claudin16 level.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective:To analyze the multi antigen distribution characteristics of Rh blood group system in Shunde area of Guangdong Province,explore the feasibility of Rh phenotype compatible blood transfusion for blood recipients in this area,and formulate the precise blood transfusion strategies.Methods:From June 2022 to December 2024,113 226 hospitalized patients scheduled for blood transfusion in Shunde Hospital of Southern Medical University and 30 832 blood donors'blood samples provided by Shunde central blood station in the same period were detected for ABO blood group and Rh phenotype by microcolumn gel method,and the Rh phenotype data of the recipients and blood donors were compared and analyzed.Results:Among 113 226 blood samples,112 963 cases(99.77％)were RhD positive,with CCDee(54.96％)and CcDEe(28.21％)phenotypes being the main phenotypes;263 cases(0.23％)were RhD negative,with ccDee(50.19％)and CcDee(36.88％)as the main phenotype.Among 30 832 blood donor samples,CCDee(54.65％)and CcDEe(27.93％)were the main phenotypes of Rh phenotype with RhD positive.The positive rates of D,C,c,E and e antigens of blood recipients and blood donors were in the same order from high to low D＞e＞C＞c＞E.The frequency of e antigen in RhD positive recipients with different ABO blood groups was statistically different from that of blood donors(P＜0.05),while there was no statistical difference in the other four antigens(P＞0.05),the distribution of ccDEe phenotypes was statistically different(P＜0.05),but there was no statistical difference in the distribution of other eight phenotypes(P＞0.05).In RhD positive recipients,the probability of finding compatible blood for phenotype CcDEe was 100％,the probability of finding compatible blood for phenotype CCDee,CCDEe and DcDee was 54％-65％,and the probability of finding compatible blood for other phenotypes was less than 10％.Providing blood with CCDee and ccDEE phenotypes according to Rh blood matching scheme can meet the needs of more than 99％of patients with 9 Rh phenotype compatible blood transfusion in this region.Conclusion:Rh phenotype detection should be carried out for hospitalized patients to be transfused,and the precise transfusion strategy of Rh phenotype isotype or compatibility should be implemented to make the transfusion treatment of patients more safe and reliable.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective:To analyze the multi antigen distribution characteristics of Rh blood group system in Shunde area of Guangdong Province,explore the feasibility of Rh phenotype compatible blood transfusion for blood recipients in this area,and formulate the precise blood transfusion strategies.Methods:From June 2022 to December 2024,113 226 hospitalized patients scheduled for blood transfusion in Shunde Hospital of Southern Medical University and 30 832 blood donors'blood samples provided by Shunde central blood station in the same period were detected for ABO blood group and Rh phenotype by microcolumn gel method,and the Rh phenotype data of the recipients and blood donors were compared and analyzed.Results:Among 113 226 blood samples,112 963 cases(99.77％)were RhD positive,with CCDee(54.96％)and CcDEe(28.21％)phenotypes being the main phenotypes;263 cases(0.23％)were RhD negative,with ccDee(50.19％)and CcDee(36.88％)as the main phenotype.Among 30 832 blood donor samples,CCDee(54.65％)and CcDEe(27.93％)were the main phenotypes of Rh phenotype with RhD positive.The positive rates of D,C,c,E and e antigens of blood recipients and blood donors were in the same order from high to low D＞e＞C＞c＞E.The frequency of e antigen in RhD positive recipients with different ABO blood groups was statistically different from that of blood donors(P＜0.05),while there was no statistical difference in the other four antigens(P＞0.05),the distribution of ccDEe phenotypes was statistically different(P＜0.05),but there was no statistical difference in the distribution of other eight phenotypes(P＞0.05).In RhD positive recipients,the probability of finding compatible blood for phenotype CcDEe was 100％,the probability of finding compatible blood for phenotype CCDee,CCDEe and DcDee was 54％-65％,and the probability of finding compatible blood for other phenotypes was less than 10％.Providing blood with CCDee and ccDEE phenotypes according to Rh blood matching scheme can meet the needs of more than 99％of patients with 9 Rh phenotype compatible blood transfusion in this region.Conclusion:Rh phenotype detection should be carried out for hospitalized patients to be transfused,and the precise transfusion strategy of Rh phenotype isotype or compatibility should be implemented to make the transfusion treatment of patients more safe and reliable.