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 relationship between 24 hour activity behaviors and fine motor development in preschool children, and to simulate the effects of reallocating time among different activity behaviors on fine motor development using isotemporal substitution analysis. Methods: From March to July 2022, a stratified cluster random sampling method was used to recruit 447 preschool children aged 3-6 years (254 boys and 193 girls) from Pingxiang City, Jiangxi Province. The 24 hour activity behaviors in preschool children were measured using ActiGraph wGT3-BT accelerometers and subjective sleep reports. Fine motor development was assessed using the Gesell Developmental Schedules. A component linear regression model was employed to analyze the impact of 24 hour activity behaviors on the development of fine motor activities, and the potential effects of adjusting activity behaviors were simulated through an isochoric substitution model. Results: The daily durations of sedentary behavior (SB) was ( 572.92 ±102.96) min (accounting for 39.79% of 24 h), the duration of light physical activity (LPA) was (131.21± 38.11 ) min ( 9.11% ), the duration of moderate to vigorous physical activity (MVPA) was (65.61±22.21) min (4.56%), and sleep duration was (670.65±57.58) min (46.82%). Sleep composition was positively associated with fine motor development ( β =2.74), while MVPA ( β =-0.84) and SB ( β =-1.93) compositions were negatively associated with fine motor development (all P <0.01). Isochoric substitution analysis showed that sleep had positive effects on the development of fine motor skills when replacing other activity behaviors (all P < 0.05), with the substitution effect for MVPA being the most significant and gradually increasing with the duration of substitution (60 min: β =28.66); sleep replacement of SB and LPA also showed positive effects (60 min: β =4.25, 2.00) (all P < 0.05). On the contrary, the substitution of sleep with MVPA showed negative effects (60 min: β =-7.86), and the substitution of LPA and SB with MVPA also showed negative effects (60 min: β =-5.65, -3.40) (all P <0.05). Conclusions The overall composition of 24 hour activity behaviors is associated with fine motor development in preschool children, with sleep playing a crucial role. Ensuring adequate sleep and optimizing the structure of activity behaviors may effectively promote the development of fine motor skills in preschool children.

Objective:To investigate the iodine nutrition status of children and pregnant women in different water iodine areas of Shandong Province.Methods:From February to September 2023, Leling City (iodine deficient), Gaotang County (moderate iodine), and Liangshan County (high iodine) in different water iodine areas of Shandong Province were selected as survey sites. One village was selected from each county (city) in five directions: east, west, south, north, and center. Forty children aged 8 to 10 years (balanced in age, half male and half female) and 20 pregnant women were selected as survey subjects in each village. Random urine samples of children and pregnant women were collected to test for urinary iodine. Meanwhile, thyroid examinations were conducted on children to calculate the goiter rate.Results:A total of 600 urine samples of children were tested, with a median urinary iodine level of 246.0 μg/L. The median urinary iodine levels of children in iodine deficient, moderate iodine and high iodine areas were 219.6, 208.0 and 446.0 μg/L, respectively ( n = 200, 200, 200). The median urinary iodine level of children in high iodine area was significantly higher than that in iodine deficient and moderate iodine areas ( P < 0.05). A total of 600 children underwent thyroid examinations, with a goiter rate of 5.8% (35/600). The goiter rate of children in iodine deficient, moderate iodine, and high iodine areas were 4.0% (8/200), 1.0% (2/200), and 12.5% (25/200), respectively. The goiter rate of children in high iodine area was significantly higher than that in iodine deficient and moderate iodine areas ( P < 0.05). A total of 247 urine samples of pregnant women were tested, with a median urinary iodine level of 158.2 μg/L. The median urinary iodine levels of pregnant women in iodine deficient, moderate iodine, and high iodine areas were 75.3, 175.2 and 321.2 μg/L, respectively ( n = 98, 84, 65). The median urinary iodine level of pregnant women in high iodine area was significantly higher than that in iodine deficient and moderate iodine areas, and the median urinary iodine level of pregnant women in moderate iodine area was significantly higher than that in iodine deficient area ( P < 0.05). Conclusion:The urinary iodine levels of children and pregnant women and the goiter rate of children in high iodine area of Shandong Province are significantly increased, and water iodine may be a key factor affecting the iodine nutrition status of the population.

To understand the background of Escherichia coli(E.coli)carried by artificially bred sika deer and the biological characteristics of the isolated strains,such as drug resistance and pathogenicity,in April 2024,we collected 184 fresh deer fecal samples from four deer farms in Luxiang Township,Shuangyang District,Changchun City,Jilin Province,for isolation and cultivation of E.coli.The isolates were tested for drug resistance and biochemical identification with a BD PhoenixTM-100 Automated Microbiology System.The virulence genes were detected with PCR,and the strains were molecularly typed with ERIC-PCR.A total of 165 E.coli strains were isolated from 184 samples of deer feces,with an isolation rate of 89.67%.Twenty strains had a drug resistance phenotype,and the drug resistance rate was 12.12%;these strains included 15 strains of multi-drug resistant bacteria and 11 strains of ESBL-producing bacteria.Virulence gene detection indicated that the sika deer isolates carried multiple diarrhea-associated virulence genes,such as EAST-1(12.12%),eae(1.21%),stx1(7.88%),stx2(7.27%),and STa(1.82%).ERIC-PCR demonstrated that the isolates showed high polymorphism.The ESBL-producing E.coli carried by sika deer are likely to spread drug resistance in the community and livestock population.Some isolates carried multiple diarrhea-associated virulence genes,thus posing a human transmission risk.Therefore,monitoring of drug resistance and virulence genes must be strengthened,and antibiotics must be used reasonably during the breeding process to avoid excessive use and misuse.

The aim of this experiment was to study the effects of different feeding modes on growth performance,blood biochemical indexes and intestinal flora of lactating Holstein male calves.Twenty-four newborn Holstein male calves with body mass of(40.00±1.01)kg and similar day old were selected and randomly divided into four groups of six calves each.The subgroups were low-milk group(LM),high-milk group(HM),high-milk milk replacer feeding group(HMR),and low-milk switching to high-milk milk replacer feeding group(CMR).The results showed that:At 45 d,the body mass of calves in the HM group was significantly higher than that of calves in the other groups(P＜0.05),and at 60 d,the body mass of calves in the HM group was significantly higher than that of calves in the LM &.CMR groups(P＜0.05).At 90 d,the body mass of calves in the LM group was significantly higher than that of calves in the HM group.Throughout the ex-perimental period,the average daily weight gain and average pellet feed intake of calves in the LM group were significantly higher than that of calves in the HM group(P＜0.05).The calf globulin level in the HMR group was significantly higher than that in the LM and HM groups(P＜0.05);the plasma immunoglobulin A level of calves in the HM group was significantly lower than that of calves in the LM and HMR groups(P＜0.05);and the plasma immunoglobulin M level of calves in the HM group was significantly higher than that of calves in the LM and CMR groups(P＜0.05),and HMR group was also significantly higher than that of LM group(P＜0.05);plasma glutathione peroxidase level of calves in HMR group was significantly higher than that of LM group(P＜0.05);plasma malondialdehyde level of calves in LM group was significantly higher than that of calves in HMR and HM groups(P＜0.05),and CMR group was also significantly higher than that of HM group(P＜0.05).Relative abundance of Thermodesulfovibrio was higher in the HM group(P＜0.05),relative abundance of Bacteroidetes in the LM group was significantly higher than that in the HMR and HM groups(P＜0.05),relative abundance of Blautia in the HM group(P＜0.05),and relative abundance of Corynebacterium in the CMR group was significantly higher than that in the LM and HM groups(P＜0.05).In summary,calves in the LM group had better weaning weights and pellet feed intake;calves in the CMR group could compensate for growth by supplemental feeding of milk replacer to obtain more optimal weaning weights and pel-let feed intake;the HMR group proved that milk-free feeding could ensure stable growth of calves;and calves in the HM group had a better pre-lactation growth performance,lower levels of oxida-tive stress,and a healthier fecal flora.

Objective:To explore the mediating effect of intrinsic motivation of nurses between empowering leadership and job performance, with the aim of providing a reference basis for managers to develop a scientific and effective intervention programme to improve nurses′ job performance.Methods:Convenience sampling method was used to select 1 213 clinical nurses from four tertiary general hospitals in Shandong Province, Henan Province, Yunnan Province, and Fujian Province from November to December 2023, and General Information Questionnaire, Empowering Leadership Scale, Intrinsic Motivation Scale, and Job Performance Scale were used to conduct a cross-sectional survey. AMOS26.0 software was used to test the mediating effect of intrinsic motivation of nurses between empowering leadership and job performance.Results:A total of 1 100 nurses completed the survey finally. Among them, there were 58 males and 1 042 females, 474 under 31 years old, 448 between 31-40 years old, and 178 over 40 years old.The total scores of the Empowering Leadership Scale, Intrinsic Motivation Scale, and Job Performance Scale were 49.44 ± 10.04, 82.35 ± 13.54 and 46.27 ± 6.20 in that order. Nurses' job performance were positive correlation with the empowered leadership and intrinsic motivation ( r=0.486, 0.703, both P<0.01), there was a positive correlation between nurse empowerment leadership and intrinsic motivation ( r=0.452, P<0.01). Nurses′ intrinsic motivation partially mediates the relationship between empowering leadership and job performance, accounting for 62.69% of the total effect. Conclusions:Intrinsic motivation of nurses is a mediating variable between empowered leadership and job performance. Nursing managers should focus on nurses' participation in autonomous decision-making to enhance nurses′ sense of competence and meaning at work, and mobilise their motivation to improve job performance.

Objective To explore the prognosis-related genes of lung adenocarcinoma(LUAD)and establish a prognostic prediction model for LUAD.Methods The differentially expressed genes of LUAD tissues and adjacent normal tissues in the GSE43458,GSE7670,and GSE140797 datasets were screened.The protein-protein interaction(PPI)network analysis,gene ontology(GO)function,Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analyses,least absolute shrinkage and selection operator for prognosis coefficient screening,disease-specific survival analysis,Cox regression analysis,and gene correlation analysis were performed.Independent prognostic genes of LUAD were screened from the differential genes,and a prognostic prediction model of LUAD was established.The expression of independent prognostic genes was analyzed,and the predictive model was evaluated by receiver operating characteristic(ROC)curve.The GSE68465 data set was used as an external validation set to verify the predictive model.Results There were 197 up-regulated differential genes and 77 down-regulated differential genes in LUAD and adjacent normal tissues common to the three datasets.Through stepwise screening,two genes,IL7R and SLC2A1,were identified as independent prognostic factors for LUAD.IL7R was an independent protective factor,while the SLC2A1 was an independent risk factor.A prediction model for curve was built with IL7R and SLC2A1.The prediction model for LUAD constructed with IL7R and SLC2A1 is as follows:Risk score=(-0.694)×expression level of IL7R+0.763×expression level of SLC2A1.Conclusion This study screened out IL7R as an independent prognostic protective factor for LUDA,and SLC2A1 as an independent prognostic risk factor for LUAD.The LUDA prediction model constructed based on these two genes has good predictive ability and generalization ability,which can provide references for the research and clinical individualized treatment of LUAD.

AIM To observe the effects of Yiqi Jiedu Tongluo Formula(YQJDTL)on renal microvascular endothelial function and prevention of renal injury in a rat model of type 2 diabetes mellitus(T2DM).METHODS The SD rats were randomly divided into a normal group and a model group.The model group was administered with high-fat diet combined with a single intraperitoneal injection of STZ to establish the T2DM model.The successfully modeled rats were randomly divided into the model group,the canagliflozin group(9 mg/kg),and the low-dose and high-dose YQJDTL groups(4.77,9.45 g/kg).The corresponding doses of the drug were administered by gavage for a total of 12 weeks,during which the rats underwent observation of their general condition and blood glucose changes.After the end of administration,the rats had their levels of renal index,24-hour UP,serum SCr,BUN,TC,TG,HDL-C,LDL-C,ET-1 and NOS measured;their changes in renal microvasculature and the degree of renal fibrosis observed using HE staining,Masson staining,PAS staining,and PASM staining;their ultrastructure of the glomeruli observed using transmission electron microscopy;their renal protein expressions of TGF-β,SMAD2,SMAD3,Col-1,VEGFA and PKC detected by immunohistochemical staining and Western blot;and their renal mRNA expressions of VEGFA,TGF-β,SMAD2 determined by RT-qPCR.RESULTS Compared with the model group,the high-dose YQJDTL group showed decreased levels of renal index,blood glucose,TG,TC,HDL,24 h UP,BUN,SCr and ET-1(P＜0.05,P＜0.01);increased LDL and NOS levels(P＜0.05,P＜0.01);reduced renal inflammatory infiltration and fibrosis degree,inhibited fusion of foot processes and thickening of basement membrane;decreased renal protein expressions of TGF-β,SMAD2,SMAD3,VEGFA,PKC and Col-1(P＜0.05,P＜0.01);and decreased mRNA expressions of VEGFA,TGF-β and SMAD2(P＜0.01).CONCLUSION In the rat models of T2DM,YQJDTL can reduce their levels of blood glucose and lipids by improving the renal indices levels and the renal microvascular endothelial functions to alleviate renal fibrosis and microangiopathy as well,and the mechanism may be associated with the down-regulated expressions of TGF-β/SMAD and VEGF pathway-related proteins.

Objective To analyze the global literature related to functional cure of hepatitis B from 2019 to 2023 by using bibliometric analysis methods,so as to help researchers understand the research hotspots and trends in this field.Methods The literature related to the topic of functional cure of hepatitis B included in the Science Citation Index Expanded(SCI-Expanded)of the Web of Science Core Collection from 2019 to 2023 was searched.By using VOSviewer and CiteSpace visual analysis tools,analyses were conducted from the perspectives of publication trends,international research cooperation networks,and keyword emergence,and were elaborated with the specific contents of the related literature to elucidate research hotspots and trends.Results A total of 600 eligible papers in this field were included.Keyword co-occurrence and thematic clustering suggested that the main research directions of functional cure were:serum biomarkers for prediction and monitoring of functional cure,functional cure and immunity,nucleoside analog discontinuation,interferon therapy,and long-term prognosis of functional cure.The research contents of the ESI highly cited original research papers were similar to the clustering of the above,but showed more attention on the novel agents for functional cure.The content of the keyword emergence map showed that hotspots of interest changed from virologic mechanisms and serum markers,to nucleoside analog discontinuation and interferon therapy,and finally to immunologic mechanisms and new drug.Conclusion The research hotspots and trends of functional cure of hepatitis B were focused on virological mechanism,serum markers,immunological mechanism,nucleoside analog discontinuation,interferon therapy,and long-term prognosis after cure.

Objective To develop a risk prediction model for ischemic stroke in symptomatic intracranial atherosclerotic stenosis(ICAS)patients based on high-resolution magnetic resonance imaging(HR-MRI)and arterial spin labeling(ASL)imaging.Methods A total of 142 patients were included and divided into acute ischemic stroke(AIS)and transient ischemic attack(TIA)groups based on stroke occurrence.Clinical risk factors,plaque characteristics,and arterial transit artifact(ATA)presence on ASL images were compared between the two groups.Multivariate logistic regression analysis was performed,incorporating clinical risk factors,plaque characteristics,and double post labeling delay(PLD)ATA presence.The predictive value of different models was compared using receiver operating characteristic(ROC)curve and DeLong tests.Results Hypertension,positive lumen remodeling,plaque enhance-ment rate,1.5 s-ATA presence,and 2.5 s-ATA presence were independent risk factors for AIS(P＜0.05).The combination of HR-MRI and ASL imaging predicted AIS most effectively[area under the curve(AUC)=0.908;95％ confidence interval(CI)0.862-0.954].No significant difference was found between the prediction performances of HR-MRI and ASL(95％CI-0.041-0.082,Z=0.659,P=0.509).Conclusion ASL is more convenient than HR-MRI for predicting ischemic stroke in ICAS patients.A model combining plaque characteristics and ATA presence effectively predicts AIS occurrence.