1.Clinical Observation on Prevention of Recurrence of Common Bile Duct Stones After ERCP with Yuyin Lidan Granules
Xiao WANG ; Yong FANG ; Cong HE ; Jiali ZHANG ; Meng YU ; Jing KONG ; Yi JIANG ; Chuanqi CHENG ; Xiaosu WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):159-166
ObjectiveTo observe the clinical efficacy and safety of Yuyin Lidan granules (YYLD) in preventing the recurrence of common bile duct stones (CBDS) in patients with liver and gallbladder dampness-heat syndrome following endoscopic retrograde cholangiopancreatography (ERCP). MethodsThis randomized, parallel, controlled trial enrolled postoperative CBDS-ERCP patients who met the inclusion and exclusion criteria. Sixty-four patients were randomly assigned to an observation group or a control group, with 32 cases in each. Both groups received conventional Western medical treatment after ERCP, while the observation group additionally received YYLD for 8 weeks. The follow-up period lasted for 1 year. The efficacy indicators included bile bilirubin levels, traditional Chinese medicine (TCM) syndrome scores, clinical efficacy rate, pancreatitis and inflammation markers, postoperative liver function, and CBDS recurrence rate at 1-year follow-up, which were used to jointly evaluate the clinical efficacy and safety of both groups. ResultsA total of 56 patients completed the study and were included in the final analysis, i.e., 29 in the observation group and 27 in the control group. Baseline characteristics were comparable between the two groups. Compared with pre-treatment and with the control group after treatment, the bile bilirubin level in the observation group significantly decreased (P<0.05). After treatment, the clinical cure and marked improvement rates were higher in the observation group than in the control group, showing a statistically significant difference in overall clinical efficacy (P<0.05). Compared with pre-treatment, the primary and secondary symptoms in the observation group, as well as the primary symptom and the secondary symptom of nausea and vomiting in the control group (weeks 4 and 8), were significantly reduced (P<0.05). Compared with the control group after treatment, the observation group showed significant reductions in the primary symptom of loose stools/constipation (day 5 and week 4) and in three secondary symptoms, i.e., bitter taste and sticky dry mouth, abdominal distension and poor appetite (throughout the treatment period), and general heaviness and fatigue (day 5 and week 4), with statistical differences (P<0.05). Compared with pre-treatment, both groups showed decreased lipase and urinary amylase levels (P<0.05). However, no significant between-group differences were observed in pancreatitis or inflammation-related indices after treatment. Compared with pre-treatment, all liver function indicators in the observation group and alanine aminotransferase ( ALT ), γ-glutamyl transferase ( γ-GT ), alkaline phosphatase (ALP), and conjugated bilirubin in the control group significantly decreased at weeks 4 and 8 (P<0.05). Compared with the control group after treatment, only serum total bilirubin and unconjugated bilirubin were significantly reduced in the observation group during the treatment period (P<0.05). ConclusionYYLD combined with conventional Western medical treatment can effectively regulate bilirubin metabolism (in bile and serum), improve TCM clinical symptoms, and prevent CBDS recurrence after ERCP in patients with liver and gallbladder dampness-heat syndrome. This regimen is safe and effective and is worthy of further clinical research and promotion.
2.Clinical Efficacy of Qi-regulating and Phlegm-removing Method(Liu Junzitang Combined with Linggang Wuwei Jiangxintang) in Treating AECOPD with Increased EOS
Renjie HUANG ; Wangqin YU ; Wuyinuo TANG ; Hong SONG ; Lyuyuan HE ; Wenbo LIN ; Guanyi WU ; Hang HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):149-156
ObjectiveTo assess the efficacy and safety of the Qi-regulating and phlegm-removing method(Liu Junzitang Combined with Linggang Wuwei Jiangxintang) for treating acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with increased eosinophils (EOS). MethodsSixty-eight AECOPD patients with increased EOS who were hospitalized in the Department of Pulmonary Diseases of Jinhua Traditional Chinese Medicine Hospital from April 2023 to April 2024 were recruited and randomly assigned to an experimental group (EG) or a control group (CG). Both groups received conventional Western medicine, with the EG additionally receiving Liujunzitang and Linggan Wuwei Jiangxintang. The therapeutic efficacy indicators were measured after the treatment. The main therapeutic efficacy indicators included partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2). The secondary efficacy indicators included the TCM symptom scores, the COPD Assessment Test (CAT) score, the Modified Medical Research Council (mMRC) Dyspnea Scale score, and the length of hospital stay. The indicators were measured at baseline and on days 3 and 7 of intervention. The safety was evaluated based on the adverse events. ResultsBaseline characteristics were not statistically different between the two groups. Compared with CG, EG showed no significant difference in PaO2 (P=0.773), PaCO2 (P=0.632) and or CAT score (P=0.336) at on day 3 but better PaO2 (P=0.004), PaCO2 (P=0.008), and CAT score (P=0.013) were significantly better at on day 7. Compared with CGAfter treatment, EG had lower TCM syndrome scores of than CG EG on day 3 (P=0.005) and day 7 were significantly decreased (P0.001). There was no significant difference in mMRC score between the two groups on day 3 (P=0.514) and day 7 (P=0.176) as wasor the length of hospital stay (P=0.915). The generalized linear mixed model (GLMM) showed that compared with CG, EG had significant improvements over time in PaO2, PaCO2, TCM syndrome symptom scores, CAT score, and mMRC score. ConclusionRegulating qi Qi and removing phlegm combined with conventional Western medicine can significantly alleviateimprove the clinical symptoms and improve the lung function of AECOPD patients with increased EOS increased AECOPDwhich has and demonstrates good safety.
3.Exploring Pathogenesis and Treatment Principles of Chronic Obstructive Pulmonary Disease Based on Spleen-mitochondria Correlation
Shiyi WANG ; Miao YU ; Xinyao HE ; Zi WANG ; Haijun LUAN ; Yibo SUN ; Haotong WANG ; Linlin WANG ; Lijian PANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):258-264
According to the Qi-blood-body fluid theory and the association between the spleen in visceral manifestation theory of traditional Chinese medicine (TCM) and mitochondria in modern cellular biology, it is proposed that the role of the spleen in generating and transforming Qi and blood is analogous to the energy-producing function of mitochondria—both serving as fundamental power sources for vital activities of the human body. The spleen governs transportation and transformation, playing a critical role in energy metabolism and the digestion and absorption of nutrients. Similarly, mitochondria are vital for maintaining physiological functions such as cellular energy supply, cell survival, and overall human metabolism. Furthermore, spleen deficiency is closely linked to mitochondrial dysfunction. Accordingly, mitochondrial energy conversion and substance metabolism are regarded as the microscopic essence of the spleen's function in transportation and transformation. Spleen deficiency and mitochondrial dysfunction contribute to the formation of pathological products such as phlegm-turbidity and blood stasis. This aligns with the pathogenesis of chronic obstructive pulmonary disease (COPD), with Qi deficiency as the root cause and phlegm-turbidity and blood stasis as the manifestations. Therefore, the integrative treatment of COPD should follow the therapeutic principle of invigorating the spleen and reinforcing healthy Qi, while also resolving phlegm and removing blood stasis to address both root cause and manifestations. This approach can improve the mitochondrial function, regulate energy metabolism, and reduce oxidative stress levels to alleviate COPD symptoms, slow down disease progression, and improve prognosis. By integrating the holistic concept of TCM with molecular mechanisms of modern medicine, this paper explores the pathogenesis and therapeutic principles of COPD from the spleen-mitochondria correlation. It not only provides a new direction for the modern development of TCM and the integration of Chinese and Western medicine but also offers a theoretical foundation for the integrated treatment of chronic, complex age-related diseases.
4.Clinical Efficacy of Qi-regulating and Phlegm-removing Method(Liu Junzitang Combined with Linggang Wuwei Jiangxintang) in Treating AECOPD with Increased EOS
Renjie HUANG ; Wangqin YU ; Wuyinuo TANG ; Hong SONG ; Lyuyuan HE ; Wenbo LIN ; Guanyi WU ; Hang HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):149-156
ObjectiveTo assess the efficacy and safety of the Qi-regulating and phlegm-removing method(Liu Junzitang Combined with Linggang Wuwei Jiangxintang) for treating acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with increased eosinophils (EOS). MethodsSixty-eight AECOPD patients with increased EOS who were hospitalized in the Department of Pulmonary Diseases of Jinhua Traditional Chinese Medicine Hospital from April 2023 to April 2024 were recruited and randomly assigned to an experimental group (EG) or a control group (CG). Both groups received conventional Western medicine, with the EG additionally receiving Liujunzitang and Linggan Wuwei Jiangxintang. The therapeutic efficacy indicators were measured after the treatment. The main therapeutic efficacy indicators included partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2). The secondary efficacy indicators included the TCM symptom scores, the COPD Assessment Test (CAT) score, the Modified Medical Research Council (mMRC) Dyspnea Scale score, and the length of hospital stay. The indicators were measured at baseline and on days 3 and 7 of intervention. The safety was evaluated based on the adverse events. ResultsBaseline characteristics were not statistically different between the two groups. Compared with CG, EG showed no significant difference in PaO2 (P=0.773), PaCO2 (P=0.632) and or CAT score (P=0.336) at on day 3 but better PaO2 (P=0.004), PaCO2 (P=0.008), and CAT score (P=0.013) were significantly better at on day 7. Compared with CGAfter treatment, EG had lower TCM syndrome scores of than CG EG on day 3 (P=0.005) and day 7 were significantly decreased (P0.001). There was no significant difference in mMRC score between the two groups on day 3 (P=0.514) and day 7 (P=0.176) as wasor the length of hospital stay (P=0.915). The generalized linear mixed model (GLMM) showed that compared with CG, EG had significant improvements over time in PaO2, PaCO2, TCM syndrome symptom scores, CAT score, and mMRC score. ConclusionRegulating qi Qi and removing phlegm combined with conventional Western medicine can significantly alleviateimprove the clinical symptoms and improve the lung function of AECOPD patients with increased EOS increased AECOPDwhich has and demonstrates good safety.
5.Exploring Pathogenesis and Treatment Principles of Chronic Obstructive Pulmonary Disease Based on Spleen-mitochondria Correlation
Shiyi WANG ; Miao YU ; Xinyao HE ; Zi WANG ; Haijun LUAN ; Yibo SUN ; Haotong WANG ; Linlin WANG ; Lijian PANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):258-264
According to the Qi-blood-body fluid theory and the association between the spleen in visceral manifestation theory of traditional Chinese medicine (TCM) and mitochondria in modern cellular biology, it is proposed that the role of the spleen in generating and transforming Qi and blood is analogous to the energy-producing function of mitochondria—both serving as fundamental power sources for vital activities of the human body. The spleen governs transportation and transformation, playing a critical role in energy metabolism and the digestion and absorption of nutrients. Similarly, mitochondria are vital for maintaining physiological functions such as cellular energy supply, cell survival, and overall human metabolism. Furthermore, spleen deficiency is closely linked to mitochondrial dysfunction. Accordingly, mitochondrial energy conversion and substance metabolism are regarded as the microscopic essence of the spleen's function in transportation and transformation. Spleen deficiency and mitochondrial dysfunction contribute to the formation of pathological products such as phlegm-turbidity and blood stasis. This aligns with the pathogenesis of chronic obstructive pulmonary disease (COPD), with Qi deficiency as the root cause and phlegm-turbidity and blood stasis as the manifestations. Therefore, the integrative treatment of COPD should follow the therapeutic principle of invigorating the spleen and reinforcing healthy Qi, while also resolving phlegm and removing blood stasis to address both root cause and manifestations. This approach can improve the mitochondrial function, regulate energy metabolism, and reduce oxidative stress levels to alleviate COPD symptoms, slow down disease progression, and improve prognosis. By integrating the holistic concept of TCM with molecular mechanisms of modern medicine, this paper explores the pathogenesis and therapeutic principles of COPD from the spleen-mitochondria correlation. It not only provides a new direction for the modern development of TCM and the integration of Chinese and Western medicine but also offers a theoretical foundation for the integrated treatment of chronic, complex age-related diseases.
6.Effect of Modified Tuoli Xiaodusan on Patients After Perianal Abscess Surgery on STAT3/VEGF Pathway
Haoyang DU ; Yuan GAO ; Haiqi FU ; Jinling HE ; Jing ZHANG ; Yangyang YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):187-195
ObjectiveTo explore the clinical efficacy of oral administration of modified Tuoli Xiaodusan on postoperative patients with perianal abscess, and its effects on related inflammatory factors and signal transducers and activators of transcription protein 3 (STAT3)/vascular endothelial growth factor (VEGF) signaling pathways. MethodsFrom January 2023 to December 2023 in Inner Mongolia hospital of traditional Chinese medicine, 60 postoperative patients with perianal abscess who met the inclusion criteria were selected. They were divided into a treatment group and a control group using the random number table method, with 30 cases in each group. The control group received conventional treatment, while the treatment group received additional treatment with modified Tuoli Xiaodusan on the basis of the control group. The course of treatment in both groups was three weeks. On the day of operation and on the 7th, 14th and 21st day after operation, enzyme-linked immunosorbent assay (ELISA) was used to measure the expression levels of serum interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Hematoxylin eosin (HE) staining was used to observe the pathological morphology of pathological tissue. Western blot was used to measure the levels of phosphorylated STAT3 (p-STAT3) and vascular endothelial growth factor (VEGF) proteins, and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to determine the expression level of VEGF mRNA. The clinical efficacy of the two groups was compared according to the wound pain, secretion volume score, and healing rate of patients on the 3rd, 7th, 14th, and 21st day after operation. ResultsThe total effective rate of the treatment group was higher than that of the control group (P<0.05). For intra-group comparison, the pain score of the control group decreased at each time period (P<0.05), and the healing rate increased (P<0.05). The secretion volume score decreased on the 14th and 21st days after operation (P<0.05). The pain score and secretion volume score of the treatment group decreased at each time period (P<0.05), and the healing rate increased (P<0.05). The levels of various inflammatory factors decreased in both groups (P<0.05). Compared with those on the surgical day, the levels of p-STAT3 and VEGF proteins in the wound tissue of the two groups were different on the 7th and 21st days after operation (P<0.05). There were significant differences in VEGF mRNA levels in wound tissue between the two groups at each time period (P<0.01). For inter-group comparison, on the 7th and 14th days after operation, the pain score in the treatment group was lower than that in the control group. On the 7th, 14th and 21st days after operation, the secretion volume scores and healing rate of the treatment group were better than those of the control group (P<0.05). The levels of various inflammatory factors in the treatment group were lower than those in the control group (P<0.05), and the decline rate was faster (P<0.05). On the 7th day after operation, the levels of p-STAT3, VEGF protein, and VEGF mRNA in the wound tissue of the treatment group were higher than those in the control group (P<0.05). HE staining showed that the inflammatory cell infiltration in the treatment group decreased faster. The cell arrangement was more orderly, and new blood vessel lumens were visible. There were no abnormalities in the safety observation indexes of all patients during the study period. ConclusionModified Tuoli Xiaodusan can relieve wound pain after perianal abscess surgery, reduce secretions, and improve wound healing rate. The mechanism may be reducing the levels of serum IL-1β, IL-6, and TNF-α, reducing the inflammatory response of the wound, upregulating the expression of p-STAT3 and VEGF proteins, and stimulating the STAT3/VEGF signaling pathway, thereby accelerating angiogenesis and promoting wound healing.
7.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.
8.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.
9.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
10.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.


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