1.The Regulatory Effects and Mechanisms of Piezo1 Channel on Chondrocytes and Bone Metabolic Dysregulation in Osteoarthritis
Yan LI ; Tao LIU ; Yu-Biao GU ; Hui-Qing TIAN ; Lei ZHANG ; Bi-Hui BAI ; Zhi-Jun HE ; Wen CHEN ; Jin-Peng LI ; Fei LI
Progress in Biochemistry and Biophysics 2026;53(3):564-576
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.
2.Research Progress on Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Knee Osteoarthritis
Jin GONG ; Jinjin ZHANG ; Lili CHEN ; Hui WANG ; Yanchao XING
Medical Journal of Peking Union Medical College Hospital 2025;16(1):75-82
Knee osteoarthritis (KOA) is a prevalent degenerative joint disease characterized by synovial inflammation, cartilage loss. Often manifesting as joint pain and limited mobility, it severely affects the quality of life of patients. Traditional treatment methods such as pharmacological injections and surgical interventions primarily aim to alleviate symptoms but have limited effects on cartilage repair. Human umbilical cord mesenchymal stem cells (hUC-MSCs), due to their anti-inflammatory and chondrogenic capabilities, is considered a new hope for the treatment of KOA. This article synthesizes the latest research findings from both domestic and international sources to discuss the theoretical basis for the clinical application of hUC-MSCs in treating KOA, clinical study design, and efficacy evaluation. It also addresses the challenges in the clinical application of hUC-MSCs and explores future directions, in the hope of providing feasible theoretical support for the treatment of KOA with hUC-MSCs.
3.Emergency medical response strategy for the 2025 Dingri, Tibet Earthquake
Chenggong HU ; Xiaoyang DONG ; Hai HU ; Hui YAN ; Yaowen JIANG ; Qian HE ; Chang ZOU ; Si ZHANG ; Wei DONG ; Yan LIU ; Huanhuan ZHONG ; Ji DE ; Duoji MIMA ; Jin YANG ; Qiongda DAWA ; Lü ; JI ; La ZHA ; Qiongda JIBA ; Lunxu LIU ; Lei CHEN ; Dong WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(04):421-426
This paper systematically summarizes the practical experience of the 2025 Dingri earthquake emergency medical rescue in Tibet. It analyzes the requirements for earthquake medical rescue under conditions of high-altitude hypoxia, low temperature, and low air pressure. The paper provides a detailed discussion on the strategic layout of earthquake medical rescue at the national level, local government level, and through social participation. It covers the construction of rescue organizational systems, technical systems, material support systems, and information systems. The importance of building rescue teams is emphasized. In high-altitude and cold conditions, rapid response, scientific decision-making, and multi-party collaboration are identified as key elements to enhance rescue efficiency. By optimizing rescue organizational structures, strengthening the development of new equipment, and promoting telemedicine technologies, the precision and effectiveness of medical rescue can be significantly improved, providing important references for future similar disaster rescues.
4.Expression and functional study of FKBP10 in oral squamous cell carcinoma
FANG Zhikai ; JIN Hui ; YANG Shan ; JIANG Nan ; ZHANG Mingyu ; ZHOU Shuang ; LI Chang ; LI Lili
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(7):529-541
Objective:
To investigate the expression and functional role of FK506 binding protein 10 (FKBP10) in oral squamous cell carcinoma (OSCC), and to provide a research basis for the estimated prognosis and targeted therapy of OSCC.
Methods:
A total of 284 OSCC samples and 19 normal samples were selected from the Cancer Genome Atlas (TCGA) database, and diagnostic analysis was performed to determine mRNA expression. Survival analysis for FKBP10 and OSCC was conducted on a gene expression profile interaction analysis website. Real-time fluorescence quantitative PCR and Western Blot were used to detect the mRNA and protein expression of FKBP10 in four OSCC cell lines and SAS and SCC9 cells transfected with siRNA. The cell proliferation ability of FKBP10-silenced cells was detected using the CCK8 method, and the cell cycle distribution and apoptosis were detected by flow cytometry. Cell migration and invasion ability were detected through wound healing and invasion experiments. The expression changes of total protein and phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT) after FKBP10 silencing were analyzed by proteomics and Western Blot.
Results:
According to the analysis of gene expression levels, the mRNA expression level of FKBP10 in OSCC was significantly higher than that in normal tissues (P < 0.001). In terms of diagnosis, the expression level of FKBP10 has unique diagnostic value for OSCC (P < 0.05). The survival analysis of FKBP10 and OSCC showed that a high expression of FKBP10 led to a decrease in patient survival and poor prognosis (P < 0.05). The expression of FKBP10 mRNA and protein in OSCC cell lines was higher than that in normal oral keratinocytes (P < 0.001). Silencing FKBP10 can reduce the proliferation, invasion, and migration ability of SAS and SCC9 (P < 0.001), and also block their cell cycle in the G0/G1 phase (P < 0.001), with a significant increase in apoptosis (P < 0.05). Protein mass spectrometry and Western blot analysis revealed that FKBP10 silencing significantly downregulated the expression of multiple proteins in the RAP1 signaling pathway, mainly RAP guanine nucleotide exchange factor 1 (RAPGEF1) (P < 0.05) and the phosphorylation of PI3K-AKT proteins (P < 0.05).
Conclusion
FKBP10 is highly expressed in OSCC, leading to poor prognosis for patients. Downregulated FKBP10 expression can inhibit the proliferation, migration, and invasion ability of OSCC cells, hinder cell cycle progression, and promote apoptosis via the RAP1-PI3K-AKT axis. FKBP10 is a potential therapeutic target and prognostic biomarker for OSCC.
5.Incremental effectiveness of two-dose of mumps-containing vaccine in chidren
Chinese Journal of School Health 2025;46(6):883-887
Objective:
To evaluate the incremental vaccine effectiveness (VE) of two dose of the mumps containing vaccine (MuCV) in chidren, so as to provide a basis for optimizing mumps immunization strategies.
Methods:
A 1∶2 frequency matched case-control study was conducted by using reported mumps cases in childcare centers or schools from Lu an, Hefei, Ma anshan and Huainan cities of Anhui Province from September 1, 2023 to June 30, 2024, as a case group(383 cases). And healthy children in the same classroom were selected as a control group(766 cases). The MuCV immunization histories of participants were collected to estimate the incremental VE of the second dose of MuCV against mumps. Group comparisons were performed using the Chi square test or t-test. For matched case-control pairs, the Cox regression model was employed to calculate the odds ratio (OR) with 95% confidence interval (CI) for two dose MuCV vaccination and to estimate the incremental vaccine effectiveness (VE).
Results:
There were no statistically significant differences between the case and control groups regarding gender, age, dosage of MuCV vaccination and the time interval since the last dose vaccination( χ 2/t=0.05, 0.20, 0.94, -0.02, P >0.05). The proportions of the case and control groups vaccinated with two doses of MuCV were 26.63% and 29.37%, respectively, and the overall incremental VE of the second dose of MuCV was 40.73% (95% CI=3.03%-63.77%, P <0.05). Subgroup analyses revealed that the incremental VE for children with a period of ≥1 year between the two doses of MuCV was 54.13% (95% CI=1.90%-78.56%, P <0.05), while for children with a period of <1 year, it was 30.63% (95% CI=-28.59%-62.58%, P >0.05). The incremental VE of the second dose of MuCV was 30.36% (95% CI=-25.95%-61.50%, P >0.05) in kindergarten children and 66.73% (95% CI=14.92%-86.99%, P <0.05) in elementary and secondary school students. The incremental VE was 28.78% (95% CI=-27.46%-60.21%, P >0.05) within five years of the last dose of MuCV vaccination and 66.07% (95% CI=-41.56%-91.87%, P >0.05) for vaccinations administered beyond five years.
Conclusions
The second dose of MuCV may offer additional protection for children; however, extending the interval between two dose of MuCV (<1 year) has shown limited incremental protective effects. Therefore, it is crucial to consider optimizing current immunization strategies for mumps.
6.Vitamin D3 mediates TIPE2 regulation of macrophage function and phenotype in chronic rhinosinusitis with nasal polyps
Xiaorong HUANG ; Hui TAN ; Juan CHEN ; Mulati KADILIYA ; Jin ZHANG ; Lunjian CHEN
Chinese Archives of Otolaryngology-Head and Neck Surgery 2025;32(5):310-315
OBJECTIVE To investigate the regulatory effect of vitamin D3(VD3)-mediated TIPE2 on macrophage function and phenotype in chronic rhinosinusitis with nasal polyps(CRSwNP).METHODS Peripheral blood samples were collected from 100 CRSwNP patients and 100 patients with simple nasal septum deviation.RT-qPCR and Western blot were used to measure the expression of TIPE2 and Arg-1,and chemiluminescence was used to measure VD3 concentration.In the J774A.1 macrophage cell line,TIPE2 was silenced,and in CRSwNP model mice,TIPE2 was overexpressed,followed by treatment with overexpressed TIPE2 combined with VD3.Western blot was used to measure the expression of TIPE2 and Arg-1,and ELISA was used to measure the expression of IL-4 and IL-13.RESULTS In the CRSwNP group,VD3 levels decreased,while TIPE2 and Arg-1 levels increased(all P<0.05).Arg-1 and TIPE2 were positively correlated(r2=0.994,P<0.05),and both were negatively correlated with VD3 levels(r2=0.652,P<0.05;r2=0.745,P<0.05).Silencing TIPE2 in J774A.1 cells led to a decrease in Arg-1,IL-4,and IL-13 levels(all P<0.05).In CRSwNP mice,overexpression of TIPE2 resulted in decreased VD3 and increased Arg-1,IL-4,and IL-13 levels,which were reversed by VD3 treatment(all P<0.05).CONCLUSION VD3 inhibits the expression of Arg-1,IL-4,and IL-13 in CRSwNP by downregulating TIPE2 expression.
7.Detection and Transfusion Strategy of Mimicking Antibodies
Hui ZHANG ; Jie-Wei ZHENG ; Sha JIN ; Wei SHEN ; Shan-Shan LI ; Xiao-Wen CHENG ; Dong XIANG
Journal of Experimental Hematology 2025;33(4):1168-1172
Objective:To explore serological detection and blood transfusion strategies of mimicking antibodies,so as to provide appropriate transfusion strategies.Methods:Detailed serological tests,including ABO blood group,Rh typing,antibody specificity,etc,were performed on two patients with autoimmune hemolytic anemia(AIHA).Meanwhile,the references about blood transfusion from mimicking antibody patients published from 1977 to 2024 in China and abroad were retrospectively summarized and analyzed.Results:The patient 1 blood type was AB,CCDee and the antibody is mimicking anti-e,transfusion the e-negative red blood cells(RBCs)was effective.After two transfusions of e-RBCs,hemoglobin levels significantly increased from 48 g/L to 91 g/L,with complete resolution of hemolytic symptoms.The patient 2 blood type was O,CcDee,and the antibody was mimicking anti-c,the patient was diagnosed with AIHA and treated with hormone.No blood products were transfused during hospitalization,and his hemolysis was relieved.Conclusion:Strictly grasping the indication of blood transfusion,blood transfusion should not be performed in the unnecessary conditions,and the corresponding antigen-negative RBC should be screened for transfusion in the necessay conditions.
8.Association between insulin resistance and idiopathic central precocious puberty in girls and the diagnostic value of insulin resistance
Jin-Bo LI ; Ya XIAO ; Shu-Qin JIANG ; Xiang-Yang LUO ; Hong-Ru ZHANG ; Jun SUN ; Wen-Hui SHI ; Ying YANG ; Wei WANG
Chinese Journal of Contemporary Pediatrics 2025;27(12):1487-1492
Objective To explore the relationship between insulin resistance and idiopathic central precocious puberty(ICPP)in girls and the diagnostic value of insulin resistance.Methods Clinical data of 245 girls aged 4 to 7.5 years with low luteinizing hormone(LH)levels(0.2-0.83 IU/L),normal body weight(body mass index standard deviation score between-2 and+2),and early breast development who visited the Department of Pediatric Endocrinology,Henan Provincial Maternal and Child Health Hospital from January 2022 to March 2025 were retrospectively analyzed.According to the Expert Consensus on the Diagnosis and Treatment of Central Precocious Puberty(2022),patients were assigned to an ICPP group(n=123)or a control group(n=122).Correlations between the homeostasis model assessment of insulin resistance(HOMA-IR)and selected indices were assessed.Multivariable logistic regression was used to evaluate the association between HOMA-IR and ICPP,and the diagnostic performance of various indices for ICPP was evaluated.Results HOMA-IR was higher in the ICPP group than in the control group(P<0.001)and was positively correlated with LH peak(rs=0.467,P<0.05)and the LH peak/FSH peak ratio(rs=0.444,P<0.05).The multivariable logistic regression model including age,BMI,and basal LH showed that HOMA-IR was closely associated with ICPP(OR=2.756,95%CI:1.940-3.913).Receiver operating characteristic curve analysis showed that the areas under the curve for basal LH,HOMA-IR,and their combination in diagnosing ICPP were 0.735,0.735,and 0.805,respectively(P<0.05),and the combined model had a greater area under the curve than either basal LH or HOMA-IR alone(both P<0.05).Conclusions HOMA-IR is closely associated with ICPP in girls with low LH and normal body weight,and combining HOMA-IR with basal LH improves early identification and diagnostic efficiency in this population.
9.Research on the operational efficiency of traditional Chinese medicine hospitals in China's Yangtze River Economic Belt in the context of high-quality development
Yi-fan MOU ; Jia-ying SUN ; Jin-ping LUO ; Bao-xuan ZHANG ; Ming-hui GENG ; Wen-qiang YIN ; Zhong-ming CHEN ; Dong-ping MA
Chinese Journal of Health Policy 2025;18(1):66-72
Objective:Based on the background of high-quality development,we analyze the operational efficiency of traditional Chinese medicine(TCM)hospitals in China's Yangtze River Economic Belt in 2021 and explore the impact of external environmental factors on operational efficiency,so as to provide a reference for promoting the high-quality development of TCM hospitals in the Yangtze River Economic Belt.Methods:The three-stage DEA model was used to analyze the operational efficiency of TCM hospitals in 11 provinces and cities in the Yangtze River Economic Zone in China in 2021.Results:After three-stage DEA analysis,the values of comprehensive efficiency,pure technical efficiency and scale efficiency of TCM hospitals in China's Yangtze River Economic Belt are 0.976,0.986 and 0.990,respectively.5 provinces and cities,Shanghai,Jiangsu,Hunan,Chongqing and Guizhou,are efficient before and after the adjustment,and the comprehensive efficiency of Zhejiang,Anhui,Hubei,Jiangxi,Sichuan and Yunnan have increased compared with that before the adjustment.Ranking of the average value of the comprehensive efficiency of TCM hospitals operation in the three major city clusters of the Yangtze River Economic Belt after adjustment:Chengdu-Chongqing city cluster(0.998)>city cluster in the Yangtze River Delta(0.964)>city cluster in the middle reaches of the Yangtze River(0.962).Conclusion:The operational efficiency of TCM hospitals in the Yangtze River Economic Zone has been underestimated,and the comprehensive efficiency is mainly affected by scale efficiency;there are differences in the operational efficiency of TCM hospitals in the three major urban agglomerations,and balanced development is needed between regions;the operational efficiency of TCM hospitals is affected by the external environment,and it is necessary to improve the external environment;it is necessary to strengthen the construction of digital and informatization of TCM,and to pay attention to the role of talents in TCM,so as to promote the high-quality development of TCM hospitals.
10.Simultaneous content determination of twenty-one constituents in Huangqi Guizhi Wuwu Decoction by HPLC-MS/MS
Qiu-gu CHEN ; Jin-ru WU ; Chang-hui LI ; Shang-bin ZHANG ; Yuan ZHAO ; Jian-ping CHEN
Chinese Traditional Patent Medicine 2025;47(2):365-371
AIM To establish an HPLC-MS/MS method for the simultaneous content determination of gallic acid,protocatechuic acid,oxypaeoniflorin,catechin,epicatechin,albiflorin,paeoniflorin,rutin,calycosin-7-glucoside,syringaldehyde,ferulic acid,coumarin,ononin,calycosin,cinnamic alcohol,cinnamic acid,benzoylpaeoniflorin,cinnamaldehyde,astragaloside,astragaloside Ⅲ,6-gingerol in Huangqi Guizhi Wuwu Decoction.METHODS The analysis was performed on a 30 ℃ thermostatic Thermo Scientific Hypersil GOLD column(150 mmx4.6 mm,3 μm),with the mobile phase comprising of 0.015%formic acid-acetonitrile flowing at 0.4 mL/min in a gradient elution manner,and electrospray ionization source was adopted in positive and negative ion modes with multiple reaction monitoring.RESULTS Twenty-one constituents showed good linear relationships within their own ranges(r>0.990 5),whose average recoveries were 93.99%-108.52%with the RSDs of 1.04%-5.97%.CONCLUSION This simple,feasible,stable and reliable method can be used for the quality control of Huangqi Guizhi Wuwu Decoction.


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