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 advances in blood-based biomarkers for moyamoya disease
Ziyang HE ; Zhi LI ; Zhang SHI ; Zhigang YANG
Chinese Journal of Clinical Medicine 2026;33(5):887-892
Moyamoya disease (MMD) is characterized by progressive stenosis or occlusion of the distal internal carotid artery and its major branches, with secondary formation of abnormal collateral vessels at the skull base. Previous studies evaluated peripheral blood molecules to reflect vascular pathology and inflammation of MMD, but their limited specificity and susceptibility to confounding factors restricted clinical utility. With advances in high-throughput omics, blood-based biomarkers with improved specificity have been identified, and bioinformatics and machine learning have facilitated biomarker screening and diagnostic model development. Meanwhile, biomarkers for different clinical scenarios have emerged, promoting a shift from “diagnostic” to “decision-making” and “predictive” biomarkers. This review summarizes recent studies in blood-based biomarkers for MMD, aiming to provide references for future in-depth studies and clinical translation.
3.Clinical efficacy of periosteal induction technique combined with sural neurovascular flap in treatment of post-traumatic osteomyelitis of calcaneus with soft tissue defect
Xiaoyong YANG ; Yongqing XU ; Xiaoyan XU ; Xiaoxiao SONG ; Xiaoqing HE ; Shunji LUO ; Junyi LI ; Zhi ZHOU ; Xijiao ZHANG ; Muguo SONG ; Jian SHI
Chinese Journal of Microsurgery 2025;48(1):7-13
Objective:To explore the clinical efficacy of periosteal induction technique combined with transfer of sural neurovascular flap in treatment of post-traumatic osteomyelitis of calcaneus with soft tissue defect.Methods:Clinical data, from January 2017 to December 2022, of 17 patients in the Army Institute for Traumatic Orthopaedics, the 920th Hospital of Joint Service Force of the Chinese People’s Liberation Amy with post-traumatic calcaneal osteomyelitis combined with soft tissue defect were retrospectively studied. The patients were 11 males and 6 females, with 46.5 (17-68) years in average. All patients received surgical treatment with periosteal induction technique in 2 phased surgies. Thorough debridement, antibiotics blended bone cement filling and wound coverage with sural neurovascular flap were carried out in phase-I surgery; The phase-II surgery were performed at 6-8 weeks after infection control to remove bone cement and then to transfer bone grafts for periosteal induction. After surgery, flap healing and infection control were observed. The infection control, pain improvement, recovery of ankle function and improvement of quality of life were evaluated by comparison of following parameters before and after surgery per phase: infection indicators [white blood cell count (WBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)], Visual Analogue Scale (VAS) score, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and MOS 36-item Short form Health Survey (SF-36, Boston Institute of Health, USA).Results:All 17 patients completed the two-phased surgical treatment, with an average interval of 9.4 (8-16) weeks between phase-I and phase-II surgery. All patients were included in the postoperative follow-up of 25.8 (13-40) months. After debridement in phase-I surgery, the sizes of soft tissue defect were found at 3.0 cm×2.0 cm-6.0 cm×8.0 cm. All flaps survived from the reconstructive surgery of sural neurovascular flap. Postoperative distal flap necroses occurred to 4 patients but all healed after further debridement. Recurrence of postoperative infection occurred to 2 patients and the infection control was achieved after the phase-I rescue surgery. Good outcomes without recurrence of infection were achieved after phase-II surgery. The postoperative follow-up at 1 year after phase-II surgery showed a statistically significant improvement of infection in blood indicators and reductions in VAS score, AOFAS ankle-hindfoot score and SF-36 score in comparison with those before surgery ( P<0.05). In addition to WBC, there were also significant differences in pairwise comparisons between each group at different time points ( P<0.05). Conclusion:In the treatment of post-traumatic calcaneal osteomyelitis with soft tissue defect, a combination of periosteal induction technique and sural neurovascular flap is beneficial to infection control, bone defect reconstruction, recovery of ankle function and improvement of quality of life.
4.Development of an artificial intelligence-based recognition model for serum indices
Shenling LIAO ; He HE ; Xia WANG ; Yifan ZHAO ; Zhi LIU ; Jin XU ; Mei ZHANG
Chinese Journal of Laboratory Medicine 2025;48(12):1546-1551
Objective:To develop an artificial intelligence-based model for automated recognition of serum indices using machine vision and deep learning.Methods:This study was a cross-sectional study.Serum sample images were collected fromWest China Hospital of Sichuan University from September 21, 2020 to January 20, 2023 using the imaging device of the fully automated sample pre-processing system. A computer random number generator was used to randomly select one whole hour each day, and all serum sample images processed within that hour were included. After excluding samples with unqualified images and missing serum index results, a total of 5, 534 samples were included. These were divided into a training set and a test set in an 8∶2 ratio using Python random shuffle function, and 4, 458 samples were in the training set and 1, 076 samples were in the test set. After manual inspection, the serum regions were annotated using the MATLAB Image Labeler tool and converted into YOLO format, and a YOLO v5-based model was constructed for automatic serum region extraction. The actual values of lipemia index (L-index), hemolysis index (H-index), and icterus index (I-index) were measured using the automatic biochemical analyzerwith matched reagent kits. A serum index regression model was constructed based on the MobileNet v2 network using the PyTorch 1.10.0 framework. The grading performance of the model was evaluated using accuracy, Kappa coefficient, sensitivity, specificity, positive predictive value, and negative predictive value. Regression performance was assessed using root mean square error (RMSE), mean absolute error (MAE), coefficient of determination (R2), and Bland-Altman analysis.Results:The overall accuracy rates for grading L-index, H-index, and I-index were 98.88%, 95.26%, and 92.47%, respectively, with Kappa coefficients of 0.72, 0.72, and 0.59. For L-index, MAE was 5.11, RMSE was 9.77, and R2 was 0.78. For H-index, MAE was 5.18, RMSE was 8.99, and R2 was 0.89. For I-index, MAE was 1.13, RMSE was 3.01, and R2 was 0.71. Bland-Altman analysis showed that 95.5%, 95.1%, and 95.7% of the data points fell within the consistency intervals for L-index, H-index, and I-index, respectively.Conclusion:The study developed an artificial intelligence-based serum index regression modelto estimate serum indices with high efficiency and accuracy. It shows great potential for reducing laboratory costs, improving clinical testing efficiency, and promoting intelligent development in laboratory medicine.
5.The value of coronary CT angiography-based traditional features and radiomics in identification of culprit plaques to cause acute myocardial infarction
Pei NIE ; Shuo ZHANG ; Yan DENG ; Shifeng YANG ; Xinxin YU ; Kaiyue ZHI ; He ZHU ; Peng LI ; Jingjing CUI ; Wenjing CHEN ; Yanmei WANG ; Yuchao XU ; Dapeng HAO ; Ximing WANG
Chinese Journal of Radiology 2025;59(9):1017-1028
Objective:To investigate the value of coronary CTA (CCTA)-based traditional features and radiomics of plaque in the identification of culprit lesions that caused acute myocardial infarction (AMI).Methods:This was a retrospective multicenter study. From July 2016 to November 2023, a total of 344 patients from the Affiliated Hospital of Qingdao University (training cohort, n=184), Shandong Provincial Hospital Affiliated to Shandong First Medical University (validation cohort, n=88) and Qilu Hospital of Shandong University (test cohort, n=72) who received percutaneous coronary intervention (PCI) due to AMI and underwent CCTA within 48 hours of AMI were enrolled. The culprit plaques and non-culprit plaques were identified using a combination of electrocardiogram, CCTA, and angiographic findings. The vessel, plaque location, plaque type, Coronary Artery Disease-Reporting and Data System (CAD-RADS) score, high-risk plaque characteristics, plaque length, plaque volume, and burden were analyzed, and 1 904 radiomics features were extracted for each plaque. The traditional imaging model, the radiomics model, and the combined model were established by using multivariate Logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each model in identifying culprit lesions. The DeLong test was used for the comparison of AUC between every two models. The net reclassification index (NRI) was used to evaluate the incremental value of the combined model to the traditional imaging model and the radiomics model. The decision curve analysis (DCA) was used to assess the clinical net benefit of these models. A correlation heatmap was used to evaluate the correlation between the radiomics score and traditional CCTA factors. The interpretable analysis of the decision process of the combined model was performed by the Shapley Additive exPlanations (SHAP). Results:In the validation cohort and the test cohort, the AUC of the traditional imaging model developed by the vessel, plaque type, positive remodeling and CAD-RADS score was 0.898 (95% CI 0.869-0.922) and 0.881 (95% CI 0.848-0.910), respectively. The radiomics model developed by six radiomics features was 0.863 (95% CI 0.831-0.891) and 0.863 (95% CI 0.827-0.864), respectively. The AUC of the combined model was 0.930 (95% CI 0.905-0.950)and 0.919 (95% CI 0.889-0.942), respectively. In the validation cohort and the test cohort, the AUC of the combined model was higher than that of the traditional imaging model ( Z=4.013, 4.272, P<0.001) and that of the radiomics model ( Z=4.819, 3.784, P<0.001), respectively. In the validation cohort, the combined model yielded an NRI of 20.43% (95% CI 10.43%-30.44%, P<0.001) and 20.21% (95% CI 9.62%-30.80%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. In the test cohort, the combined model yielded an NRI of 28.05% (95% CI 16.72%-39.38%, P<0.001) and 23.57% (95% CI 13.58%-33.56%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. DCA showed the combined model had the highest clinical net benefit. The correlation heatmap showed the radiomics score was not correlated or only weakly correlated with traditional CCTA factors. SHAP indicated the radiomics and CAD-RADS score contributed significantly to the model. Conclusion:The CCTA-based traditional features and radiomics of plaque have favorable performance for the identification of culprit plaques in patients with AMI.
6.Creation and Exploration of the"Organized Fill-in-the-Blank Format"Disci-pline Construction Model for Forensic Medicine in the New Era
Zhi-Wen WEI ; Hong-Xing WANG ; Jun-Hong SUN ; Hao-Liang FAN ; Hong-Liang SU ; Le-Le WANG ; Wen-Ting HE ; Zhe CHEN ; Jie ZHANG ; Xiang-Jie GUO ; Ji LI ; Geng-Qian ZHANG ; Xin-Hua LIANG ; Jiang-Wei YAN ; Qiang-Qiang ZHANG ; Cai-Rong GAO ; Ying-Yuan WANG ; Hong-Wei WANG ; Jun XIE ; Bo-Feng ZHU ; Ke-Ming YUN
Journal of Forensic Medicine 2025;41(1):25-29
Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.
7.Prevalence and risk factors of training-related abdominal injuries: A multicenter survey study.
Chuan PANG ; Wen-Quan LIANG ; Gan ZHANG ; Ting-Ting LU ; Yun-He GAO ; Xin MIAO ; Zhi-Da CHEN ; Yi LIU ; Wen-Tong XU ; Hong-Qing XI
Chinese Journal of Traumatology 2025;28(4):301-306
PURPOSE:
This study aims to identify the prevalence and risk factors of military training-related abdominal injuries and help plan and conduct training properly.
METHODS:
This questionnaire survey study was conducted from October 2021 to May 2022 among military personnel from 6 military units and 8 military medical centers and participants' medical records were consulted to identify the training-related abdominal injuries. All the military personnel who ever participated in military training were included. Those who refused to participate in this study or provided an incomplete questionnaire were excluded. The questionnaire collected demographic information, type of abdominal injury, frequency, training subjects, triggers, treatment, and training disturbance. Chi-square test and t-test were used to compare baseline information. Univariate and multivariate regression analyses were used to explore the risk factors associated with military training-related abdominal injuries.
RESULTS:
A total of 3058 participants were involved in this study, among which 1797 (58.8%) had suffered training-related abdominal injuries (the mean age was 24.3 years and the service time was 5.6 years), while 1261 (41.2%) had no training-related abdominal injuries (the mean age was 23.1 years and the service time was 4.3 years). There were 546 injured patients (30.4%) suspended the training and 84 (4.6%) needed to be referred to higher-level hospitals. The most common triggers included inadequate warm-up, fatigue, and intense training. The training subjects with the most abdominal injuries were long-distance running (589, 32.8%). Civil servants had the highest rate of abdominal trauma (17.1%). Age ≥ 25 years, military service ≥ 3 years, poor sleep status, and previous abdominal history were independent risk factors for training-related abdominal injury.
CONCLUSION
More than half of the military personnel have suffered military training-related abdominal injuries. Inadequate warm-up, fatigue, and high training intensity are the most common inducing factors. Scientific and proper training should be conducted according to the factors causing abdominal injuries.
Humans
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Military Personnel
;
Risk Factors
;
Prevalence
;
Male
;
Abdominal Injuries/etiology*
;
Female
;
Adult
;
Surveys and Questionnaires
;
Young Adult
8.One-year recovery after lateral retinaculum release combined with chondroplasty in patients with lateral patellar compression syndrome.
Zhen-Long LIU ; Yi-Ting WANG ; Jin-Ming LIN ; Wu-Ji ZHANG ; Jiong-Yuan LI ; Zhi-Hui HE ; Yue-Yang HOU ; Jian-Li GAO ; Wei-Li SHI ; Yu-Ping YANG
Chinese Journal of Traumatology 2025;28(6):462-468
PURPOSE:
Lateral patellar compression syndrome (LPCS) is characterized by a persistent abnormally high stress exerted on the lateral articular surface of the patella due to lateral patellar tilt without dislocation and lateral retinaculum contracture, leading to anterior knee pain. The purpose of this study is to evaluate the efficacy and prognosis of lateral retinaculum release (LRR) combined with chondroplasty in the treatment of LPCS.
METHODS:
This retrospective study evaluated 40 patients who underwent LRR combined with chondroplasty for LPCS between 2020 and 2021. The assessment included improvement in postoperative tenderness and knee joint function. Patients were evaluated using the Lysholm, Tegner, and International Knee Documentation Committee 2000 scoring systems, as well as the visual analog scale, both preoperatively and postoperatively, with the paired comparisons analyzed using a t-test. Additionally, intraoperative observations were made regarding knee joint lesions, including cartilage damage and osteophyte formation, with analysis by the Chi-square test.
RESULTS:
The visual analog scale score for tenderness showed a significant decrease after surgery (p < 0.001). Evaluation of knee joint function also indicated significant improvements, as demonstrated by increased Lysholm, Tegner, and International Knee Documentation Committee 2000 scores postoperatively (p < 0.001, p = 0.011, p < 0.001, respectively). Furthermore, all LPCS patients included in the study presented with cartilage injuries and osteophyte formation. Significant differences were noted in the incidence of cartilage damage and osteophyte formation at different locations within the knee among patients with LPCS.
CONCLUSION
LRR combined with chondroplasty is an effective surgical approach for treating patients with LPCS, with satisfactory recovery observed at the 1-year follow-up. Additionally, the incidence of cartilage damage and osteophyte formation in LPCS patients varies significantly depending on the specific location within the knee joint.
Humans
;
Male
;
Female
;
Retrospective Studies
;
Adult
;
Middle Aged
;
Patella/surgery*
;
Knee Joint/physiopathology*
;
Recovery of Function
;
Young Adult
;
Treatment Outcome
;
Cartilage, Articular/surgery*
;
Adolescent
9.Pharmacological actions of the bioactive compounds of Epimedium on the male reproductive system: current status and future perspective.
Song-Po LIU ; Yun-Fei LI ; Dan ZHANG ; Chun-Yang LI ; Xiao-Fang DAI ; Dong-Feng LAN ; Ji CAI ; He ZHOU ; Tao SONG ; Yan-Yu ZHAO ; Zhi-Xu HE ; Jun TAN ; Ji-Dong ZHANG
Asian Journal of Andrology 2025;27(1):20-29
Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male
;
Epimedium/chemistry*
;
Humans
;
Genitalia, Male/drug effects*
;
Flavonoids/therapeutic use*
;
Animals
10.Icariin targets PDE5A to regulate viability, DNA synthesis and DNA damage of spermatogonial stem cells and improves reproductive capacity.
Tian-Long LIAO ; Cai-Mei HE ; Di XIAO ; Zhi-Rong ZHANG ; Zuping HE ; Xiao-Ping YANG
Asian Journal of Andrology 2025;27(4):543-549
Icariin is a pure compound derived from Epimedium brevicornu Maxim, and it helps the regulation of male reproduction. Nevertheless, the role and underlying mechanisms of Icariin in mediating male germ cell development remain to be clarified. Here, we have demonstrated that Icariin promoted proliferation and DNA synthesis of mouse spermatogonial stem cells (SSCs). Furthermore, surface plasmon resonance iron (SPRi) and molecular docking (MOE) assays revealed that phosphodiesterase 5A (PDE5A) was an important target of Icariin in mouse SSCs. Mechanically, Icariin decreased the expression level of PDE5A. Interestingly, hydrogen peroxides (H 2 O 2 ) enhanced the expression level of phosphorylation H2A.X (p-H2A.X), whereas Icariin diminished the expression level of p-H2A.X and DNA damage caused by H 2 O 2 in mouse SSCs. Finally, our in vivo animal study indicated that Icariin protected male reproduction. Collectively, these results implicate that Icariin targets PDE5A to regulate mouse SSC viability and DNA damage and improves male reproductive capacity. This study thus sheds new insights into molecular mechanisms underlying the fate decisions of mammalian SSCs and offers a scientific basis for the clinical application of Icariin in male reproduction.
Male
;
Animals
;
Flavonoids/pharmacology*
;
Mice
;
Cyclic Nucleotide Phosphodiesterases, Type 5/drug effects*
;
DNA Damage/drug effects*
;
Cell Survival/drug effects*
;
Cell Proliferation/drug effects*
;
Spermatogonia/drug effects*
;
Reproduction/drug effects*
;
Adult Germline Stem Cells/metabolism*
;
DNA Replication/drug effects*

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