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 of biomaterial-mediated brain-computer interfaces in neural rehabilitation
Xiangxiang YU ; Jie SHI ; Yucheng CHEN ; Lifeng CHENG ; Liangcan HE ; Kai LI
Chinese Journal of Clinical Medicine 2026;33(2):213-220
Neurological disorders such as post-stroke hemiplegia, spinal cord injury, and Parkinson disease represent a major global health burden. Brain-computer interface (BCI), which creates direct communication pathways between the nervous system and external devices, offers a promising strategy for functional restoration. The long-term efficacy of such BCI fundamentally depends on the performance of biomaterials at the neural interface. Ideal materials must concurrently satisfy biocompatibility, electrical conductivity, enduring chemical stability, and mechanical compatibility with brain tissue. This review systematically outlines the application of conductive polymers, inorganic nanomaterials, natural biomaterials, and composites in BCI, with a focus on how advanced designs, such as bionic and encapsulated electrodes, improve signal fidelity and surgical feasibility through structural innovation. It further summarizes key material-modification techniques and analyzes the complex foreign-body response orchestrated by microglia, astrocytes, and peripheral immune cells. Finally, it provides insights into future research directions and clinical translation of BCI-based neurorehabilitation, while highlighting critical challenges including long-term biosafety and the establishment of standardized evaluation frameworks, aiming to bridge the gap between laboratory innovation and effective clinical deployment.
3.Characterization and Application of Moisture Absorption Kinetics of Traditional Chinese Medicines Based on Double Exponential Model:A Review
Yanting YU ; Lei XIONG ; Yan HE ; Wei LIU ; Jing YANG ; Yao ZHANG ; Jiali CHEN ; Xiaojian LUO ; Xiaoyong RAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):340-346
Hygroscopicity research has long been a key focus and hot topic in Chinese materia medica(CMM). Elucidating hygroscopic mechanisms plays a vital role in formulation design, process optimization, and storage condition selection. Hygroscopic models serve as essential tools for characterizing CMM hygroscopic mechanisms, with various types available. The double exponential model is a kinetic mathematical model constructed based on the law of conservation of energy and Fick's first law of diffusion, tailored to the physical properties of CMM extracts. In recent years, this model has been extensively applied to simulate the dynamic moisture absorption behavior of CMM extracts and solid dosage forms under varying humidity conditions. It has revealed the correlation between moisture absorption kinetic parameters and material properties, offering a new perspective for characterizing the moisture uptake behavior of CMM. This paper systematically reviews the application progress of this model in the field of CMM, analyzes its advantages, disadvantages, and challenges in this domain, and explores its potential application trends in other fields. It aims to provide references for elucidating the moisture absorption mechanisms of CMM and researching moisture-proofing technologies, while also offering insights for its broader application in food and polymer materials.
4.A prediction model for mild cognitive impairment risk among the elderly
MA Zongkang ; LIU Xinglang ; LI Huihui ; HE Guowei ; YAN Ping ; ZHANG Chuanrong ; MA Xuan ; CHE Yajie ; YU Shan ; CHEN Fenghui
Journal of Preventive Medicine 2026;38(2):124-129
Objective:
To develop a prediction model for mild cognitive impairment (MCI) risk among the elderly, so as to provide a tool for MCI early screening.
Methods :
From July 2022 to September 2024, a multi-stage stratified random cluster sampling method was used to recruit permanent residents aged ≥65 years from the Xinjiang Uygur Autonomous Region as study participants. Data on sociodemographic characteristics, nutritional status, body composition indices, bone mineral density, and handgrip strength were collected through questionnaires and physical examinations. Sarcopenia was defined based on appendicular skeletal muscle index and handgrip strength. MCI was assessed using the Mini-Mental State Examination, with adjustments for educational level. Participants were randomly divided into a training set and a validation set in a 7∶3 ratio. LASSO regression and multivariable logistic regression models were employed to screen for predictors and construct an MCI risk prediction model. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curve and decision curve analysis (DCA).
Results:
A total of 1 641 participants were surveyed, including 755 males (46.01%) and 886 females (53.99%). The majority of participants were aged 65-<75 years, comprising 1 154 individuals (70.32%). MCI was detected in 517 participants, corresponding to a detection rate of 31.51%. Resultsfrom LASSO regression and multivariate logistic regression analysis showed that residence (rural, OR = 2.323, 95% CI: 1.682-3.210), age (75-<85 years, OR = 1.405, 95% CI: 1.019-1.937; ≥85 years, OR = 3.655, 95% CI: 1.696-7.875), educational level (primary school, OR = 0.341, 95% CI: 0.247-0.472; junior high school, OR = 0.255, 95% CI: 0.160-0.408; high school, OR = 0.286, 95% CI: 0.154-0.531; bachelor's degree or above, OR = 0.120, 95% CI: 0.041-0.351), history of alcohol consumption (yes, OR = 3.216, 95% CI: 2.164-4.779), risk of malnutrition (yes, OR = 1.464, 95% CI: 1.064-2.014), sarcopenia (yes, OR = 3.197, 95% CI: 2.332-4.385), and waist-to-hip ratio (abnormal, OR = 1.540, 95% CI: 1.159-2.048) were identified as predictive factors for MCI among the elderly. In the training set, the area under the ROC curve, sensitivity, and specificity were 0.788, 0.719, and 0.712, respectively. In the validation set, the corresponding values were 0.784, 0.913, and 0.542, respectively. DCA demonstrated that the model provided a higher clinical net benefit for predicting MCI risk when the risk threshold probability ranged from 0.124 to 0.764.
Conclusion
The prediction model developed in this study demonstrates good discriminative ability and clinical utility, indicating its substantial value for predicting the MCI risk among the elderly.
5.Analysis of a three-generation Chinese pedigree affected with Hereditary spastic paraplegia type 3A due to variant of ATL1 gene.
Zhenhua GONG ; Fengjuan HE ; Changshui CHEN ; Yu AN
Chinese Journal of Medical Genetics 2026;43(2):129-135
OBJECTIVE:
To explore the genetic basis for a Chinese pedigree affected with Hereditary spastic paraplegia type 3A (SPG3A) and the genotype-phenotype correlation.
METHODS:
A three-generation pedigree presented at Huantai Maternal and Child Health Care Hospital in March 2021 was selected as the study subject. Whole-exome sequencing (WES) and pedigree analysis was carried out. Candidate variant was validated by Sanger sequencing of the members from the pedigree. Haplotype analysis was used to trace the origin of the variant, and pathogenicity was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2025-12).
RESULTS:
A c.1024C>T (p.Pro342Ser) variant of the ATL1 was identified in the four affected members, including the proband, but none of the three unaffected relatives. Haplotype analysis suggested that the variant was derived from the proband's mother and has co-segregated with the disease phenotype. Based on the guidelines of the ACMG, it was classified as likely pathogenic.
CONCLUSION
The ATL1 c.1024C>T (p.Pro342Ser) variant probably underlay the pathogenesis in this pedigree. Above finding has enriched the mutational spectrum of ATL1 and phenotypic spectrum of SPG3A in the Chinese population, and enabled genetic counseling for this pedigree.
Humans
;
Pedigree
;
Spastic Paraplegia, Hereditary/genetics*
;
Male
;
Female
;
Asian People/genetics*
;
Adult
;
Haplotypes
;
Membrane Proteins/genetics*
;
Exome Sequencing
;
GTP-Binding Proteins/genetics*
;
Mutation
;
Middle Aged
;
China
;
Genetic Association Studies
;
East Asian People
6.The role of shed syndecan-4 in temporomandibular joint osteoarthritis in rats
HE Kangping ; CHEN Xiaohua ; LI Jinru ; ZHAN Ying ; HE Feng ; JIANG Tianlu ; LI Feifei ; YU Shibin
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(5):443-455
Objective:
To investigate the mechanism of shed syndecan-4 (sSDC4) in temporomandibular joint osteoarthritis (TMJOA) in rats, aiming to provide experimental evidence for its prevention and treatment.
Methods:
This study was approved by the Institutional Animal Ethics Committee. Twelve 6-week-old female Sprague Dawley (SD) rats were randomly divided into two groups. They received a single intra-articular injection into the bilateral superior cavity of temporomandibular joint, which consisted of either 50 μL of 4 mg/mL monosodium iodoacetate (TMJOA model group) or 50 μL of phosphate-buffered saline (PBS, control group). After 4 weeks, the mandibular condylar cartilage was harvested for hematoxylin & eosin (H&E) staining, Safranin O-fast green (SO) staining, and type II collagen (Col-Ⅱ) immunohistochemical staining to assess the degree of cartilage degeneration. The synovium of the temporomandibular joint was collected for immunohistochemical staining to detect the expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) to evaluate the degree of synovial inflammation. Synovial fluid from the temporomandibular joint cavity was collected to measure sSDC4 levels by enzyme-linked immunosorbent assay (ELISA). In addition, 12 6-week-old female SD rats were randomly divided into a His-SDC4 group and a control group, receiving injections into the bilateral superior cavity of temporomandibular joint of either 100 ng/mL (50 μL) of His-SDC4 protein or 50 μL of PBS once every 3 days for a total of 28 days. The same experimental procedures were performed for H&E staining, SO staining, and immunohistochemical staining (Col-Ⅱ IL-6, TNF-α) to observe condylar cartilage degeneration and detect synovial inflammation. Rat synovial fibroblasts and condylar chondrocytes were cultured in vitro and randomly divided into a His-SDC4-stimulated (10 ng/mL) group and control group. Perform CCK-8 cytotoxicity assays and observe cellular morphology under optical microscopy, the mRNA expression levels of IL-6 and TNF-α were detected by real-time quantitative polymerase chain reaction (RT-qPCR), and the levels of IL-6 and TNF-α in cell culture supernatants were measured by ELISA.
Results:
Compared with the control group, the TMJOA group showed decreased condylar cartilage thickness, percentage of SO-positive area, and percentage of Col-Ⅱ-positive area (all P<0.001); an increased synovitis score (P<0.001) and increased percentages of IL-6- and TNF-α-positive cells in the synovium (all P<0.001); and a significant increase in sSDC4 levels in the synovial fluid (P=0.011). Following intra-articular injection of His-SDC4, condylar cartilage thickness, percentage of SO-positive area, and percentage of Col-Ⅱ-positive area all decreased (all P<0.001); the synovitis score increased (P=0.006), and the percentages of IL-6- and TNF-α-positive cells in the synovium increased (all P<0.001). In vitro experiments showed that His-SDC4 stimulation significantly upregulated the expression levels of IL-6 and TNF-α in both synovial fibroblasts and condylar chondrocytes (all P<0.01), and the levels of these two cytokines in the culture supernatants also significantly increased (all P<0.01).
Conclusion
During TMJOA progression, the level of sSDC4 in the synovial fluid is significantly elevated, which can directly stimulate synovial fibroblasts and condylar chondrocytes to secrete more pro-inflammatory cytokines, forming a vicious cycle that accelerates TMJOA progression.
7.Predicting the surgical difficulty,complications and prognosis of kidney tumors based on anatomical features:advances in renal tumor scoring systems
Gen LI ; Yuhao YU ; Xuexing FAN ; Jincheng LI ; Jiasong LI ; Pugui LI ; Xiaopen CHEN ; He WANG ; Geng ZHANG ; Yong WANG
Journal of Modern Urology 2025;30(4):355-363
Renal tumor scoring systems can describe the anatomical characteristics of renal tumors. It is an important standard to evaluate the surgical complexity and to evaluate the surgical complexity and feasibility of partial nephrectomy. Scholars at home and abroad have established various scoring systems based on different anatomical parameters,such as R.E.N.A.L.,PADUA,C-Index,which are used to guide the clinical selection of surgical modalities,and predict perioperative complications and prognosis. In this paper,various scoring systems are grouped into three major categories according to their functions:prediction of surgical complexity,prediction of complications,and prediction of prognosis. The contents,characteristics and clinical application value of various renal tumor scoring systems are introduced in detail to guide urologists,enhance their surgical decision-making ability,and improve the clinical outcomes.
8.Diet and lifestyle factors influencing comorbidity of cardiovascular disease in elderly diabetic patients in community
Yawen HE ; Tongneng XUE ; Yu CHEN
Journal of Public Health and Preventive Medicine 2025;36(4):137-140
Objective To investigate the effect of diet and lifestyle on cardiovascular comorbidity in elderly diabetic patients in community. Methods A total of 437 elderly patients with diabetes mellitus in a community of Huai'an City were divided into comorbidity group and non-comorbidity group according to the presence or absence of cardiovascular comorbidity. Dietary and lifestyle data were collected by self-designed questionnaires. The differences between the two groups were compared. Multivariate logistic regression was used to analyze the influencing factors of comorbidity of diabetes mellitus with cardiovascular disease. Results Among the surveyed patients, 184 (42.11%) had at least one comorbidity of cardiovascular disease, with the most common diseases being hypertension in 93 patients (21.28%), coronary heart disease in 71 patients (16.25%), and stroke in 42 patients (9.61%). Multivariate logistic regression analysis showed that: the risk of comorbidity in the male group was 1.528 times higher than that in the female group; the risk of comorbidity among individuals with inadequate carbohydrate intake was 1.520 times higher than that of individuals with adequate carbohydrate intake; the risk of comorbidity in the group with smoking history > 30 years was 1.299 times higher than that in the group ≤ 30 years; the risk of comorbidity was 49.80% lower in the group with tea preference than that in the group without tea preference; and the risk of comorbidity in the group not meeting the standard for exercise was 1.492 times higher than that in the group meeting the standard for exercise. All these differences were statistically significant (P<0.05). Conclusion The comorbidity of cardiovascular disease in elderly diabetic patients in community should not be ignored, and targeted dietary and lifestyle interventions are helpful for the prevention and control of comorbidity.
9.Analysis of Animal Model of Type 2 Diabetes Mellitus Based on Clinical Characteristics of Traditional Chinese and Western Medicine
Xiangning HUANG ; Weiyi LEI ; Yifan SHI ; Tingyi HE ; Nianqing CHEN ; Yilin XU ; Rong YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):211-219
Based on the etiology and clinical diagnostic criteria of type 2 diabetes mellitus (T2DM), identification and typing of treatment from the perspective of traditional Chinese and western medicine, the criteria for evaluating the clinical compatibility of traditional Chinese and western medicine in animal models of T2DM were set up. The literature was reviewed to sort out and analyze the existing commonly used modeling methods, summarize the mechanism, compare the advantages and disadvantages, and calculate the consistency between the animal model and the clinical symptoms, syndromes, and indicators from the perspective of traditional Chinese and western medicine. The authors found that spontaneous animal models and high-fat diets combined with multiple low-dose streptozotocin (STZ) induction models were more in line with modern medical pathogenesis of T2DM. However, it fails to form some special syndromes required for traditional Chinese medicine (TCM) research. In addition, there are many methods of combining the etiology and pathogenesis of TCM, which can be divided into three categories: intervention carried out by drug administration, behavioral stimulation, or environmental changes according to TCM, or use of hormones according to clinical evidence and combination of the two methods mentioned above. All of them can successfully establish different types of animal models. However, different methods of establishing syndrome models have their own advantages and disadvantages, and there is no unified standard for the stability and evaluation of syndrome models. As for the clinical consistency criteria of traditional Chinese and western medicine established in this paper, the animal model with 100% consistency has not been calculated due to the conditions of incomplete symptoms and syndromes described in the studies and different selection indicators. Consequently, the establishment of a simple, easy-to-use, and affordable T2DM animal model with both traditional Chinese and western medicine disease characteristics and the improvement of the Chinese and western medicine evaluation system for different evidence types are of great significance for the future development of TCM research on T2DM.
10.Analysis of Animal Model of Type 2 Diabetes Mellitus Based on Clinical Characteristics of Traditional Chinese and Western Medicine
Xiangning HUANG ; Weiyi LEI ; Yifan SHI ; Tingyi HE ; Nianqing CHEN ; Yilin XU ; Rong YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):211-219
Based on the etiology and clinical diagnostic criteria of type 2 diabetes mellitus (T2DM), identification and typing of treatment from the perspective of traditional Chinese and western medicine, the criteria for evaluating the clinical compatibility of traditional Chinese and western medicine in animal models of T2DM were set up. The literature was reviewed to sort out and analyze the existing commonly used modeling methods, summarize the mechanism, compare the advantages and disadvantages, and calculate the consistency between the animal model and the clinical symptoms, syndromes, and indicators from the perspective of traditional Chinese and western medicine. The authors found that spontaneous animal models and high-fat diets combined with multiple low-dose streptozotocin (STZ) induction models were more in line with modern medical pathogenesis of T2DM. However, it fails to form some special syndromes required for traditional Chinese medicine (TCM) research. In addition, there are many methods of combining the etiology and pathogenesis of TCM, which can be divided into three categories: intervention carried out by drug administration, behavioral stimulation, or environmental changes according to TCM, or use of hormones according to clinical evidence and combination of the two methods mentioned above. All of them can successfully establish different types of animal models. However, different methods of establishing syndrome models have their own advantages and disadvantages, and there is no unified standard for the stability and evaluation of syndrome models. As for the clinical consistency criteria of traditional Chinese and western medicine established in this paper, the animal model with 100% consistency has not been calculated due to the conditions of incomplete symptoms and syndromes described in the studies and different selection indicators. Consequently, the establishment of a simple, easy-to-use, and affordable T2DM animal model with both traditional Chinese and western medicine disease characteristics and the improvement of the Chinese and western medicine evaluation system for different evidence types are of great significance for the future development of TCM research on T2DM.


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