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.

[摘 要] 目的：系统评价CD19 CAR-T细胞免疫疗法对比标准治疗在复发/难治性弥漫性大B细胞淋巴瘤（R/R DLBCL）患者中疗效与安全性，通过探索性分析探索不同CAR-T细胞产品对疗效的潜在影响，为临床治疗决策提供循证参考。方法：计算机检索中国知网、万方数据库、维普期刊数据库、中国生物医学文献数据库、PubMed、Embase和Cochrane Library数据库，搜集CD19 CAR-T细胞疗法对比标准治疗用于R/R DLBCL的随机对照试验（RCT），检索时限均为建库至2025年10月25日。由2位研究者独立进行文献筛选、数据提取和质量评价，采用R4.2.2软件进行Meta分析。结果：共纳入2项Ⅲ期RCT研究（ZUMA-7、TRANSFORM），各结局指标均根据异质性检验结果选择固定效应模型合并数据。疗效方面，CD19 CAR-T细胞疗法可显著改善患者无事件生存期（HR=0.455，95%CI：0.363~0.570，P < 0.001）和降低死亡风险（HR = 0.738，95%CI：0.575~0.947，P = 0.017）；同时可显著提高完全缓解率（RR = 1.879，95%CI：1.574~2.242，P < 0.001）。按产品类型的探索性分析显示，liso-cel和axi-cel均优于标准治疗（liso-cel：HR = 0.380，95%CI：0.260~0.540，P < 0.001；axi-cel：HR = 0.510，95%CI：0.380~0.680，P < 0.001），但该分析为不同试验间的对比，证据等级有限。安全性结局显示：CAR-T细胞疗法的免疫效应细胞相关神经毒性综合征（ICANS）发生率显著升高（RR = 22.387，95%CI：4.353~115.132，P < 0.001）；≥3级细胞因子释放综合征（CRS）发生率数值升高（RR = 8.181，95%CI：0.935~71.574，P = 0.058），差异无统计学意义。纳入研究的偏倚风险整体为低；敏感性分析证实结果稳健。结论：基于2项RCT的Meta分析结果，CD19 CAR-T细胞（liso-cel/axi-cel）可作为R/R DLBCL二线治疗的选择之一，其疗效优于标准治疗，且特征性不良反应（CRS/ICANS）经规范管理后可控，可根据患者基线状态个体化选择CAR-T细胞产品。本研究证据基础薄弱，上述结论尚需更多高质量、大样本RCT验证。

Objective: To examine the prevalence of e-cigarette use and associated factors among primary and secondary school students in Pudong New Area, Shanghai, and to explore the pathways linking harm perception of e-cigarettes, interpersonal social influence, and attitudes toward e-cigarette use with experimentation behavior, in order to provide scientific basis for further optimizing the prevention and control strategies of e-cigarette among adolescents. Methods: From September to October 2025, a multi stage cluster random sampling method was used to select 5 144 primary and secondary school students aged 8-19 years from 47 primary and secondary schools in Pudong New Area, Shanghai, to conduct an anonymous questionnaire survey. The questionnaire collected information on e-cigarette use, harm perception of e-cigarette, interpersonal social influence, and attitudes toward e-cigarette use. The Chi-square test was applied to analyze the differences in cigarette and e-cigarette use behavior among primary and secondary school students with different demographic characteristics. Structural equation modeling (SEM) was constructed using Mplus 8.3 software, and the bootstrap method was utilized to test the mediating effects. Results: The reported rates of cigarette experimentation, e-cigarette experimentation, and current e-cigarette use among primary and secondary school students were 1.85%, 2.10%, and 0.70%, respectively. Higher reporting rates of e-cigarette experimentation were observed among boys (2.82%), secondary school students aged 16-19 (3.39%), senior high school students (3.05%), and those with weekly pocket money >100 yuan ( 6.11% ) ( χ 2=11.67, 8.61, 8.00, 54.18, all P <0.05). Structural pathway analysis results demonstrated that e-cigarette harm perception positively predicted interpersonal social influence ( β =0.61) and e-cigarette use attitude ( β = 0.53 ), and interpersonal social influence ( β =0.65) and e-cigarette use attitude ( β =0.25) further promoted e-cigarette experimentation behavior among primary and secondary school students (all P <0.01), with interpersonal social influence playing a major mediating role (indirect effect=0.40). Conclusions E-cigarette experimentation behavior among primary and secondary school students in Pudong New Area is jointly influenced by multiple psychosocial factors. Intervention strategies should strengthen interpersonal social factors such as family and peers on the basis of health education, thereby constructing a comprehensive prevention and control strategy for e-cigarette use among primary and secondary school students.

BACKGROUND:Ursolic acid can promote the directed differentiation of bone marrow mesenchymal stem cells into osteoblasts.However,there are few reports on whether ursolic acid has osteogenic effect on human periodontal ligament stem cells. OBJECTIVE:To investigate the effect of ursolic acid on proliferation and osteogenic differentiation of human periodontal ligament stem cells. METHODS:The human periodontal ligament stem cells were isolated and cultured.Passage 3 cells were selected and treated with ordinary medium containing different concentrations(0,1,2,4,6,8 μmol/L)of ursolic acid.After intervention for 1,3,5,7 days,the cell proliferation was detected by CCK-8 assay and the appropriate intervention concentration was screened.Passage 3 human periodontal ligament stem cells were treated with osteogenic induction solution containing 0,1,2,4 μmol/L ursolic acid,respectively.After 7 days of intervention,the mRNA expressions of alkaline phosphatase,Runx2,and osteocalcin were detected by qRT-PCR.After 14 days of intervention,the formation of mineralized nodules was observed by alizarin red staining.Passage 3 human periodontal ligament stem cells were taken and the control group was added with osteogenic induction solution;the ursolic acid group and the antagonist group were added with osteogenic induction solution containing ursolic acid(2 μmol/L)and the bone morphogenetic protein signaling pathway antagonist Noggin,respectively.The ursolic acid+antagonist group was added with osteogenic induction solution containing ursolic acid(2 μmol/L)and Noggin,the inhibitor of bone morphogenetic protein signaling pathway,and cultured for 7 days.qRT-PCR and western blot assay were used to detect the mRNA and protein expressions of bone morphogenetic protein 2,Smad1,osteopontin,and Runx2. RESULTS AND CONCLUSION:(1)1,2,4 μmol/L ursolic acid could promote the proliferation of human periodontal ligament stem cells.6,8 μmol/L ursolic acid could inhibit the proliferation of human periodontal ligament stem cells,and 1,2,4 μmol/L ursolic acid was selected to intervene in subsequent experiments.(2)Compared with 0 μmol/L,1,2,4 μmol/L ursolic acid could promote the expression of alkaline phosphatase,Runx2,and osteocalcin mRNA and the formation of mineralized nodules(P<0.05),and the effect of 2 μmol/L ursolic acid was the most significant.(3)Compared with the control group,the mRNA and protein expressions of bone morphogenetic protein 2,Smad1,osteopontin,and Runx2 in the ursolic acid group were increased(P<0.05),while mRNA and protein expressions of the above indexes were decreased in the antagonist group(P<0.05).Compared with the ursolic acid group,mRNA and protein expressions of above indexes were decreased in ursolic acid+antagonist group(P<0.05).(4)The results indicate that ursolic acid promotes osteogenic differentiation of human periodontal ligament stem cells through bone morphogenetic protein signaling pathway.

Houpo Qiwutang originated from the Synopsis of the Golden Chamber， and it consists of seven medicines： Magnoliae Officinalis Cortex， Rhei Radix et Rhizoma， Aurantii Fructus Immaturus， Cinnamomi Ramulus， Zingiberis Rhizoma Recens， Glycyrrhizae Radix et Rhizoma， and Jujubae Fructus. It is a basic formula for the treatment of abdominal fullness. Through the bibliometric method， the historical history， drug base， preparation and dosage， decoction method， and ancient and modern applications of Houpu Qiwu Tang were analyzed by means of textual research. The research finds that Houpu Qiwu Tang has been passed down through the generations in an orderly manner with fewer changes. The drug base of this formula is basically clear， and the base of Magnoliae Officinalis Cortex， Rhei Radix et Rhizoma， Cinnamomi Ramulus， Zingiberis Rhizoma Recens， and Jujubae Fructus is consistent with the 2020 edition of Chinese Pharmacopoeia. The mainstream base of Aurantii Fructus Immaturus is the dried young fruit of Citrus aurantium of Rutaceae family， and the historical mainstream base of Glycyrrhizae Radix et Rhizoma is the dried root of Glycyrrhiza uralensis of Leguminosae family. The modern dosage of this formula is 110.40 g of Magnoliae Officinalis Cortex， 41.40 g of Rhei Radix et Rhizoma， 69 g of Aurantii Fructus Immaturus， 27.60 g of Cinnamomi Ramulus， 69 g of Zingiberis Rhizoma Recens， 41.40 g of Glycyrrhizae Radix et Rhizoma， and 30 g of Jujubae Fructus. In addition， the decoction method is to add 2 000 mL of water with the above seven flavors of the medicine， boil it to 800 mL， and then take 160 mL in a warm state each time. The amount of the medicine taken for each time is 22.08 g of Magnoliae Officinalis Cortex， 8.28 g of Rhei Radix et Rhizoma， 13.80 g of Aurantii Fructus Immaturus， 5.52 g of Cinnamomi Ramulus， 13.80 g of Zingiberis Rhizoma Recens， 8.28 g of Glycyrrhizae Radix et Rhizoma， and 6 g of Jujubae Fructus. The modern application of this formula involves the digestive system， respiratory system， and urinary system. It is more advantageous in digestive system diseases such as early postoperative inflammatory bowel obstruction， functional dyspepsia， gastric pain， functional abdominal distension， and gastric reflux esophagitis. By comprehensively examining the key information of Houpu Qiwu Tang， this paper aims to provide literature support for the development and clinical application of this formula.

Objective: To investigate the situation and influencing factors of school bullying experienced by primary and middle school students, so as to provide the basis for formulating school bullying intervention measures and promoting students' physical and mental health development. Methods: All the counties (cities, districts) in Zhejiang Province were stratified to urban and suburban areas, primary, junior high and senior high school students were selected using a stratified cluster sampling method. Basic information, lifestyle and school bullying were collected through questionnaire surveys. Factors affecting school bullying experienced by primary and middle school students were analyzed using a multivariable logistic regression model. Results: Totally 137 846 valid questionnaires were recovered, with an effective recovery rate of 97.17%. There were 72 526 males (52.61%) and 65 320 females (47.39%). There were 47 561 primary school students (34.50%), 47 701 junior high school students (34.61%) and 42 584 senior high school students (30.89%). A total of 3 987 students suffered from school bullying, accounting for 2.89%. The proportions of being maliciously teased, being intentionally excluded from group activities/isolated, being teased about physical defects or appearance, being hit/kicked/pushed/shoved/locked in a room, being threatened, and being extorted for money were 2.04%, 1.18%, 1.11%, 0.86%, 0.84% and 0.83%, respectively. Multivariable logistic regression analysis showed that the students who were males (OR=1.122, 95%CI: 1.048-1.202), lived in suburban areas (OR=1.322, 95%CI: 1.233-1.418), lived in areas with medium (OR=1.086, 95%CI: 1.006-1.173) or underdeveloped (OR=1.298, 95%CI: 1.191-1.415) economic level, had higher academic levels (junior high school, OR=1.380, 95%CI: 1.270-1.499; senior high school, OR=1.210, 95%CI: 1.083-1.351), lived on campus (OR=1.489, 95%CI: 1.372-1.616), engaged in fights (OR=6.029, 95%CI: 5.585-6.509), attempted to smoke (OR=1.320, 95%CI: 1.128-1.545), drank (OR=1.735, 95%CI: 1.575-1.912), were scolded and beaten by parents (OR=1.972, 95%CI: 1.822-2.135) and were obese (OR=1.240, 95%CI: 1.132-1.360) were more likely to experience school bullying. Conclusion The harm of school bullying to the physical and mental health of primary and middle school students should be taken seriously, and active policy measures should be adopted to strengthen intervention.

The prevention and research of military training injuries(MTI)are crucial for reducing non-battle casualties,ensuring combat readiness,and enhancing the effectiveness of military training.In-depth analyses of the prevention and treatment strategies of MTI and related research can provide concrete guidance for scientific training practices.As a critical component of national defense,the Chinese Navy has experienced rapid development in recent years,and the prevention and research of MTI in naval forces have become a key focus.In recent years,rehabilitation medicine has been increasingly recognized for its importance in areas such as physical capability enhancement and injury prevention.The comprehensive adoption of rehabilitation concepts and the early implementation of rehabilitation measures have been widely accepted.It has important guiding significance for further strengthening the application of rehabilitation in preventing and treating injuries in naval training.This article discusses how to further strengthen the rehabilitation strategies for the prevention and research of MTI in the Navy,so as to provide insights and prospects for this field.

Objective To compare the clinical efficacy and safety of transarterial chemoembolization(TACE)plus apatinib(Apa)and camrelizumab(Cam)and TACE plus Apa in treating CNLC stage Ⅲ hepatocellular carcinoma(HCC).Methods A total of 54 patients in Affiliated Yancheng No.1 People's Hospital,School of Medicine,Nanjing University with CNLC stage Ⅲ HCC were enrolled in this study.The patients were divided into triple treatment group(n=25,receiving TACE plus Apa and Cam)and dual treatment group(n=29,receiving TACE plus Apa).The overall survival(OS)and progression-free survival(PFS)were compared between the two groups.Univariate analysis and multivariate analysis were used to determine the independent influencing factors for OS and PFS.The target immunotherapy-related adverse reactions(TRAE)were analyzed.Results The median OS and PFS in the triple treatment group were 23.2 months and 10.9 months respectively,which were higher than 15.2 months and 5.8 months respectively in the dual treatment group(both P＜0.001).Multivariate analysis indicated that the therapeutic regimen and the type of portal vein tumor thrombosis(PVTT)were the independent factors affecting OS,while only the therapeutic regimen was the independent factor affecting PFS.The incidence of≥grade Ⅲ TRAE in the triple treatment group and the dual treatment group was 20％(5/25)and 17.2％(5/29)respectively,the difference between the two groups was not statistically significant(P＞0.05).Conclusion For the treatment of patients with CNLC stage Ⅲ HCC,TACE plus Apa and Cam is superior to TACE plus Apa in OS and PFS,and the type of PVTT and the therapeutic regimen are the independent prognostic factors associated with patient's survival.

Transcatheter aortic valve replacement(TAVR)has emerged as a well-established treatment for severe aortic stenosis.Acute infective endocarditis(AIE)represents a rare severe com-plication following this procedure.Currently,there are no definitive guideline recommendations for management of such infective endocarditis(IE).This study presented a case of delayed thrombosis after TAVR,which subsequently developed into AIE.The patient eventually underwent surgical treat-ment and showed significant improvement.

The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs (lncRNAs). However, the dynamics of lncRNA expression during human tooth development remain poorly understood. In this research, we examined the lncRNAs present in the dental epithelium (DE) and dental mesenchyme (DM) at the late bud, cap, and early bell stages of human fetal tooth development through bulk RNA sequencing. Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis. Specific lncRNAs expressed in the DE and DM, such as PANCR, MIR205HG, DLX6-AS1, and DNM3OS, were identified through a combination of bulk RNA sequencing and single-cell analysis. Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ, such as the inner enamel epithelium and coronal dental papilla (CDP). Functionally, we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells. These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
Humans ; RNA, Long Noncoding/metabolism* ; Odontogenesis/genetics* ; Tooth Germ/embryology* ; Cell Differentiation ; Gene Expression Regulation, Developmental ; Mesoderm/metabolism* ; Tooth/embryology* ; Gene Expression Profiling ; Sequence Analysis, RNA ; Dental Pulp/cytology*