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 explore the effectiveness of the generative large language model MedGo in nursing decision-making for elderly patients with multimorbidity. Methods A quasi-randomized controlled trial study was conducted involving 6 junior nurses, 6 senior nurses and the MedGo model from January 1, 2025 to March 31, 2025 at the Emergency Internal Medicine Ward of Shanghai East Hospital Affiliated to Tongji University. Clinical data of 120 elderly patients with multimorbidity were analyzed to compare the performance of the three groups in four tasks (nursing diagnosis assessment, nursing intervention formulation, complication identification, and complication prevention) from three evaluation dimensions: decision-making time consumption, decision accuracy, and decision-making quality. Results In terms of decision-making time, the senior nurse group completed all four tasks faster than the junior nurse group (P＜0.01), and the MedGo group completed all four tasks faster than the junior nurse group (P＜0.001) and the senior nurse group (P＜0.001). In terms of decision-making accuracy, senior nurse group scored higher than junior nurse group in all four tasks (P＜0.001), while the MedGo group outperformed the senior nurse group only in complication identification (P＜0.001). In terms of decision-making quality, the MedGo group scored higher than junior nurse group (P＜0.001) and senior nurse group (P＜0.001) in all four tasks. Conclusions The MedGo model demonstrates advantages of high efficiency, accuracy, and quality in nursing decision-making for elderly patients with multimorbidity; senior nurses outperform junior nurses in decision-making, providing diverse references for clinical nursing decision-making.

OBJECTIVE To develope a predictive model for medication deviation risks during the hospital-to-home transition period in coronary heart disease （CHD） patients with initial treatment， aiming to assist medical staff in rapidly identifying high-risk groups for medication deviation. METHODS A total of 462 CHD patients with initial treatment from the Affiliated Hospital of North China University of Science and Technology （hereinafter referred to as “our hospital”） between January and July 2024 were enrolled. The patients were randomly divided into a modeling group and an internal validation group. The modeling group was further categorized into a medication deviation group and a non-medication deviation group based on whether medication deviations occurred. Similarly， 57 CHD patients with initial treatment from the cardiology department of our hospital between June and September 2025 were collected as an external validation group. Univariate analysis was used to screen predictive factors， followed by multivariate Logistic regression to construct the predictive model. Internal validation methods were employed to evaluate model performance， while external validation methods were used to test the model’s generalizability. RESULTS The 462 patients were divided into a modeling group （319 cases） and an internal validation group （143 cases）. In the modeling group， the medication deviation group （192 cases， 60.19%） and the non-medication deviation group （127 cases， 39.81%） were identified. Multivariate Logistic regression analysis revealed that age， medication type， medication adherence， and self-efficacy in rational medication use were predictive factors for medication deviations in CHD patients with initial treatment （ P ＜0.05）. The predictive model equation was logit P ＝ln[ P /（1－ P ） ] ＝1.321+1.732×age+4.091×medication type －4.360×medication adherence －3.081×self-efficacy in rational medication use. The model demonstrated good discrimination， with a Hosmer-Lemeshow goodness-of-fit test P -value of 0.439， an area under the receiver operating characteristic curve （AUC） of 0.870， sensitivity of 0.970， and specificity of 0.607. A risk nomogram with a total score of 350 points and a cutoff value of 110 points was plotted. The internal validation group showed an AUC o f 0.787 and a prediction accuracy of 77.6%， while the external validation group exhibited an AUC of 0.802 and a prediction accuracy of 73.7%. CONCLUSIONS This study successfully developed a predictive model for medication deviation risks during the hospital-to-home transition period in CHD patients with initial treatment. The model demonstrates excellent discrimination and predictive accuracy， effectively identifying high-risk populations for medication deviations. Age （＞70 years）， number of drug types≥5， poor medication adherence， and poor self-efficacy in rational medication use are independent risk factors for medication deviations.

Objective To investigate the application value of bedside ultrasound monitoring of quadriceps muscle changes in mechanically ventilated children in the early treatment of ICU-acquired muscle weakness (ICU-AW). Methods Eighty-two pediatric ICU patients with mechanical ventilation for>48 hours were selected. On the day of admission (D₀) and on day 7 (D₇), bedside ultrasound was performed to measure the thickness and cross-sectional area of the rectus femoris and vastus intermedius muscles. Patients were classified using Medical Research Council scores into control group (n = 63) and muscle weakness group (n = 19). Muscle parameters and atrophy rates were compared between groups. Diagnostic performance was assessed using receiver operating characteristic curves. Results The incidence of ICU-AW was 23.17%. At both D₀ and D₇, the average thickness of the rectus femoris, the average thickness of the vastus intermedius, the average area of the rectus femoris, and the average area of the vastus intermedius were significantly different between the two groups (P<0.05). The atrophy rates of the thickness of the rectus femoris and the area of the vastus intermedius were lower in the control group than in the muscle weakness group at both D₀ and D₇ (P<0.05). The area under the receiver operating characteristic curve for quadriceps parameters in diagnosing ICU-AW was 0.871, with a sensitivity of 89.47% and a specificity of 79.37%. Conclusion Bedside ultrasound dynamic monitoring of quadriceps changes enables early identification of ICU-AW and provides a basis for clinical intervention.

[Objective] To compare the clinical efficacy of super pulse thulium laser enucleation of the prostate (SPThuLEP) with "open tunnel" and transurethral holmium laser enucleation of the prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH), in order to provide reference for the treatment options of BPH. [Methods] The clinical data of 112 BPH patients treated in our hospital during Jan.2023 and Jul.2023 were retrospectively analyzed, including 65 treated with SPThuLEP with "open tunnel" and 57 with HoLEP.The operation time, postoperative hemoglobin decrease, postoperative bladder irrigation, catheter indwelling time, hospitalization time and complications were compared between the two groups.The changes of maximum urine flow rate (Qmax), international prostate symptom score (IPSS), quality of life score (QoL), postvoid residual (PVR) and prostate-specific antigen (PSA) were compared between the two groups before operation and one month after operation. [Results] All operations were successful without conversion to open or transurethral plasmakinetic resection.The postoperative decrease of hemoglobin in SPThuLEP group was lower than that in HoLEP group [(13.12±6.72) g/L vs. (21.02±6.51) g/L], with statistical difference (P<0.05). There were no significant differences in the operation time [(63.35±15.73) min vs.(61.02±17.55) min], postoperative bladder irrigation time [(1.07±0.45) d vs. (1.06±0.36) d], catheter indwelling time [(2.98±0.56) d vs. (3.01±0.63) d] and hospitalization time [(3.63±0.61) d vs.(3.79±0.76) d] between the two groups (P>0.05). No blood transfusion, secondary bleeding or unplanned hospitalization occurred, and there were no serious complications such as transurethral electroresection syndrome (TURS), urethral stricture and urinary incontinence.One month after operation, the Qmax, IPSS, QoL, PVR and PSA of the two groups were significantly improved compared with those before operation (P<0.05), but with no statistical difference between the two groups (P>0.05). [Conclusion] SPThuLEP with "open tunnel" has comparable efficacy as HoLEP in the treatment of BPH.With advantages of small amount of bleeding and high safety, this minimally invasive technique can be widely popularized in clinical practice.

OBJECTIVE: To provide preimplantation genetic testing (PGT) for a patient with Incontinentia pigmenti (IP) due to IKBKG gene variant but without family samples through construction of single nucleotide polymorphism (SNP)-based haplotype by Long-read sequencing (LRS) technology. METHODS: A female IP patient with a heterozygous IKBKG c.1167dup variant but without family genetic data who sought genetic counseling at Women and Children' Hospital of Ningbo University in November 2021 was selected as the study subject. The IKBKG gene has a highly homologous pseudogene IKBKGP1. Genomic DNA was extracted from peripheral blood samples from the couple, and LRS was used to obtain informative SNP loci flanking the variant locus, enabling the construction of SNP haplotype with a long segment spanning from the non-homologous region of IKBKG to the variant site. Trophoblast cells were biopsied from blastocysts fertilized through intracytoplasmic sperm injection, and next-generation sequencing (NGS) was used to determine the SNP information of the embryos. Linkage analysis with the parental SNP haplotypes was conducted to detect the carrier status of the embryos and exclude chromosomal aneuploidies. Sanger sequencing was carried out to validate the result. A euploid embryo without the pathogenic variant was selected for transfer. Prenatal diagnosis was carried out by amniocentesis at mid-trimester to verify the result of PGT tests, and follow-up was conducted after the baby was born. This study has been approved by the Ethics Committee of Women and Children's Hospital of Ningbo University (Ethics No. EC2023-094). RESULTS: A total of seven blastocysts were tested, and PGT results indicated that two embryos were euploid and did not carry the pathogenic variant. One euploid embryo was transferred, which resulted in a singleton pregnancy. Amniocentesis at 24 weeks of gestation confirmed that the status of fetal IKBKG gene, and its chromosomal status was consistent with the PGT results. A healthy male infant was born at 38+6 weeks of gestation. CONCLUSION For IP patients with de novo mutation or without family genetic samples, PGT with LRS can directly construct the SNP-based haplotype while avoiding interference from pseudogenes, providing an effective strategy for PGT.
Female ; Humans ; Male ; Pregnancy ; Genetic Testing/methods* ; Haplotypes/genetics* ; High-Throughput Nucleotide Sequencing/methods* ; I-kappa B Kinase/genetics* ; Incontinentia Pigmenti/diagnosis* ; Polymorphism, Single Nucleotide/genetics* ; Preimplantation Diagnosis/methods* ; Infant, Newborn

AIM To investigate the improvement effects of Poria cocos polysaccharides(PCPs)on mouse nonalcoholic fatty liver disease(NAFLD).METHODS Forty-eight C57BL/6 mice were randomly divided into the blank group,the model group,the simvastatin group(4 mg/kg)and the high,medium and low dose PCPs groups(200,100 and 50 mg/kg),with 8 mice in each group.The NAFLD model was reproduced by 16 weeks feeding of high-fat and high-cholesterol diet,followed by 8 weeks administration of corresponding drug by gavage.The mice had their body mass and liver coefficient assessed;their levels of hepatic free fatty acid(FFA),and serum total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),aspartate aminotransferase(AST),alanine aminotransferase(ALT),γ-glutamyltransferase(γ-GT)and malondialdehyde(MDA)detected;their hepatic pathological changes and lipid deposition observed using HE staining,NAFLD activity score(NAS)and oil red O staining;and their hepatic protein expressions of Akt,mTOR,p-Akt,p-mTOR and SREBP-1c detected by Western blot.RESULTS Compared with the blank group,the model group demonstrated all increased body weight,liver coefficient,hepatic FFA level,and serum TC,TG,LDL-C,AST,ALT,γ-GT,MDA,IL-1β and TNF-α.levels(P＜0.05,P＜0.01);decreased HDL-C level and activities of SOD and GSH-Px(P＜0.05,P＜0.01);more obvious hepatic pathological damage as revealed by increased NAS score(P＜0.01)and increased lipid deposition area(P＜0.01).Compared with the model group,the groups intervened with high or medium dose PCPs,or simvastatin displayed decreased body weight,liver coefficient,hepatic FFA level,and serum TC,TG,LDL-C,AST,ALT,γ-GT,MDA,IL-1β and TNF-α levels(P＜0.05,P＜0.01);increased HDL-C level and SOD,GSH-Px activities(P＜0.05,P＜0.01);decreased hepatic pathological damage as revealed by the decreased NAS score and lipid deposition area(P＜0.05,P＜0.01);and decreased hepatic protein expressions of p-Akt,p-mTOR and SREBP-1c protein(P＜0.05)as well.CONCLUSION PCPs can improve mouse NAFLD,and its mechanism may lie in their function in reversing abnormal lipid metabolism via Akt/mTOR/SREBP-1c signaling pathway.

Objective To form an expert consensus on nasogastric tube and intestinal tube placement in children(hereinafter referred to as the"consensus"),and provide a reference for pediatric medical workers regarding the operation of gastrointestinal tube placement in children.Methods A"consensus"formulation group was established.The"5.0"EBHC Pyramid Model was employed to systematically search,evaluate,summarize and extract relevant evidence to form the initial draft of the"consensus".The RAND-UCLA expert consensus method was utilized.Through a round of expert inquiries by correspondence and a round of face-to-face expert discussions,the data were collated,analyzed,refined,and modified to form the final version of the"consensus".Results The effective recovery rate of the expert inquiry questionnaire was 100％.The coefficient of expert authority(Cr)was 0.891.The Kendall's concordance coefficient of the inquiries was 0.692(P＜0.01),which was statistically significant.The median of the"RAND-UCLA"suitability score were 7-9 points,and the disagreement index(DI)value was＜1.00.The final"consensus"encompasses 9 aspects,including qualification requirements for the tube placement personnel,indications and contraindications,preoperative assessment,preoperative preparation,measurement of tube length,key points of tube placement,methods for confirming the position,tube flushing,fixation,and recording,with 47 recommendations.Conclusion This"consensus"is scientific,rigorous,and practical,covering all links of the gastrointestinal tube placement process in children,providing reference and guidance for the safe and standardized implementation of gastrointestinal tube placement in children.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

AIM:To investigate the effects of high-dose methotrexate(MTX)on alkaline phosphatase(ALP)and the effects of ALP changes on bone me-tabolism,bone marrow granulogram function,liver function and excretion.METHODS:Aspartate ami-notransferase(AST),alanine aminotransferase(ALT)and albumin(ALB)were used as liver function indi-cators,serum calcium(Ca)and phosphorus(P)were used as bone metabolism indicators,neutro-phil(ANC)and white blood cell count(WBC)were used as bone marrow granuloline function indica-tors,and methotrexate C48h concentration ≥1 μmol/L was used as the excretion delay.One-way ANOVA analysis was performed on the ALP levels before and after the first chemotherapy and the second chemotherapy,and the children were divided into normal group and low group according to the ALP level,and the seven indexes before and after che-motherapy were quantitatively and qualitatively an-alyzed,and univariate and multivariate Logistic re-gression analysis was performed on the concentra-tion of methotrexate C48h and the above indexes in the children treated with the second chemothera-py.RESULTS:After the first chemotherapy and the second chemotherapy,ALP was significantly de-creased[(204.0±83.6)U/L vs.(172.8±67.3)U/L,(179.4±59.3)U/L vs.(169.6±57.1)U/L,all P＜0.05],and the serum Ca,P,ANC,WBC,and ALB were sig-nificantly decreased(P＜0.05),and AST and ALT were increased(P＜0.05),and ALT was an indepen-dent risk factor for delayed excretion(OR=1.049,95％CI 1.023-1.077,P＜0.001),ALB was an indepen-dent protective factor for delayed excretion(OR=0.551,95％CI 0.460-0.660,P＜0.001),and ALP was not a significant contributor to MTX excretion de-lay.CONCLUSION:ALP is not a good predictor of liv-er function and bone marrow granulopathy func-tion due to a significant decrease in ALP caused by high-dose MTX,and ALP together with serum calci-um and phosphorus levels can constitute an early warning indicator of bone metabolism disorders.