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.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

ObjectiveTo investigate the mechanism of ferroptosis mediated by long-chain acyl-CoA synthetase 4 （ACSL4） signalling pathway in rats with coronary heart disease with blood stasis syndrome and the intervention effect of Xuefu Zhuyutang. MethodsSPF male SD rats were randomly divided into normal group， sham-operation group， model group， trimetazidine group （5.4 mg·kg^-1）， low-， medium-， and high-dose group （3.51， 7.02，14.04 g·kg^-1） of Xuefu Zhuyutang. The coronary artery left anterior descending ligation method was used to prepare a model of coronary heart disease with blood stasis syndrome， and continuous treatment for 7 d was conducted， while the sham-operation group was only threaded and not ligated. The general macroscopic symptoms of the rats were observed， and indicators such as electrocardiogram， echocardiography， and blood rheology were detected. The pathological morphology of myocardial tissue was observed by hematoxylin-eosin （HE） staining， and the changes in mitochondria in myocardial tissue were observed by transmission electron microscopy. The level of iron deposition in myocardial tissue was observed by Prussian blue staining. The levels of 12-hydroxyeicosatetraenoic acid （12-HETE） and 15-HETE were detected in serum by enzyme-linked immunosorbent assay. A biochemical colourimetric assay was used to detect the levels of Fe²⁺， lipid peroxidation （LPO）， glutathione （GSH）， and T-GSH/glutathione disulfide （GSSG） in myocardial tissue. DCFH-DA fluorescence quantitative assay was employed to detect the levels of reactive oxygen species （ROS）. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was adopted to detect the protein and mRNA expressions of glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， ACSL4， and ly-sophosphatidylcholine acyltransferase3 （LPCAT3） in myocardial tissue. ResultsCompared with those in the normal group， the rats in the model group were poor in general macroscopic symptoms. The electrocardiogram showed widened QRS wave amplitude and increased voltage， bow-back elevation of the ST segments， elevated T waves， J-point elevation， and accelerated heart rate. Echocardiography showed a significant reduction in left ventricular ejection fraction （LVEF） and left ventricular fraction shortening （LVFS） （P<0.01）. Blood rheology showed that the viscosity of the whole blood （low， medium， and high rate of shear） was significantly increased （P<0.01）. HE staining showed an abnormal structure of myocardial tissue. There was a large area of myocardial necrosis and inflammatory cell infiltration and a large number of connective tissue between myocardial fibers. Transmission electron microscopy showed that the mitochondria were severely atrophy or swelling. The cristae were reduced or even broken， and the matrix was flocculent or even vacuolated. Prussian blue staining showed that there were a large number of iron-containing particles， and the iron deposition was obvious. The content of 12-HETE and 15-HETE in the serum was significantly increased （P<0.01）. The content of Fe²⁺， LPO， and ROS in myocardial tissue was significantly increased （P<0.01）. The content of GSH was significantly decreased （P<0.01）， and T-GSH/GSSG was decreased （P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 in myocardial tissue were both significantly decreased （P<0.05， P<0.01）， while those of ACSL4 and LPCAT3 increased significantly （P<0.01）. Compared with the model group， the general macroscopic symptoms and electrocardiogram results of rats in low-， medium- and high-dose groups of Xuefu Zhuyutang were alleviated， and the differences in LVEF/LVFS ratios were all significantly increased （P<0.05， P<0.01）. The differences in whole-blood viscosity （low， medium， and high rate of shear） were all significantly decreased （P<0.01）. The results of HE staining and transmission electron microscopy showed that the morphology， structure， and mitochondria of cardiomyocytes were improved. The content of 12-HETE and 15-HETE in serum was reduced to different degrees in low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. The content of Fe²⁺， LPO， and ROS was significantly reduced in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and the content of GSH and T-GSH/GSSG was significantly increased （P<0.05， P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 were significantly increased to varying degrees in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and ACSL4 and LPCAT3 were decreased to different degrees in the low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can regulate iron metabolism and anti-lipid oxidation reaction to mediate ferroptosis through the ACSL4 signalling pathway， thus exerting a protective effect on rats with coronary heart disease with blood stasis syndrome.

Objective: This study aimed to explore the correlation between balance function and core muscle activation in patients with adolescent idiopathic scoliosis (AIS), compared to healthy individuals. Methods: A total of 24 AIS patients and 25 healthy controls were recruited. The limits of stability (LOS) test were conducted to assess balance function, while surface electromyography was used to measure the activity of core muscles, including the internal oblique, external oblique, and multifidus. Diaphragm thickness was measured using ultrasound during different postural tasks. Center of pressure (COP) displacement and trunk inclination distance were also recorded during the LOS test. Results: AIS patients showed significantly greater activation of superficial core muscles, such as the internal and external oblique muscles, compared to the control group (p < 0.05). Diaphragm activation was lower in AIS patients during balance tasks (p < 0.01). Although no significant difference was observed in COP displacement between the groups, trunk inclination was significantly greater in the AIS group during certain tasks (p < 0.05). Conclusion These findings suggest distinct postural control patterns in AIS patients, highlighting the importance of targeted interventions to improve balance and core muscle function in this population.

Objective: This study aimed to explore the correlation between balance function and core muscle activation in patients with adolescent idiopathic scoliosis (AIS), compared to healthy individuals. Methods: A total of 24 AIS patients and 25 healthy controls were recruited. The limits of stability (LOS) test were conducted to assess balance function, while surface electromyography was used to measure the activity of core muscles, including the internal oblique, external oblique, and multifidus. Diaphragm thickness was measured using ultrasound during different postural tasks. Center of pressure (COP) displacement and trunk inclination distance were also recorded during the LOS test. Results: AIS patients showed significantly greater activation of superficial core muscles, such as the internal and external oblique muscles, compared to the control group (p < 0.05). Diaphragm activation was lower in AIS patients during balance tasks (p < 0.01). Although no significant difference was observed in COP displacement between the groups, trunk inclination was significantly greater in the AIS group during certain tasks (p < 0.05). Conclusion These findings suggest distinct postural control patterns in AIS patients, highlighting the importance of targeted interventions to improve balance and core muscle function in this population.

Objective: This study aimed to explore the correlation between balance function and core muscle activation in patients with adolescent idiopathic scoliosis (AIS), compared to healthy individuals. Methods: A total of 24 AIS patients and 25 healthy controls were recruited. The limits of stability (LOS) test were conducted to assess balance function, while surface electromyography was used to measure the activity of core muscles, including the internal oblique, external oblique, and multifidus. Diaphragm thickness was measured using ultrasound during different postural tasks. Center of pressure (COP) displacement and trunk inclination distance were also recorded during the LOS test. Results: AIS patients showed significantly greater activation of superficial core muscles, such as the internal and external oblique muscles, compared to the control group (p < 0.05). Diaphragm activation was lower in AIS patients during balance tasks (p < 0.01). Although no significant difference was observed in COP displacement between the groups, trunk inclination was significantly greater in the AIS group during certain tasks (p < 0.05). Conclusion These findings suggest distinct postural control patterns in AIS patients, highlighting the importance of targeted interventions to improve balance and core muscle function in this population.

Objective: This study aimed to explore the correlation between balance function and core muscle activation in patients with adolescent idiopathic scoliosis (AIS), compared to healthy individuals. Methods: A total of 24 AIS patients and 25 healthy controls were recruited. The limits of stability (LOS) test were conducted to assess balance function, while surface electromyography was used to measure the activity of core muscles, including the internal oblique, external oblique, and multifidus. Diaphragm thickness was measured using ultrasound during different postural tasks. Center of pressure (COP) displacement and trunk inclination distance were also recorded during the LOS test. Results: AIS patients showed significantly greater activation of superficial core muscles, such as the internal and external oblique muscles, compared to the control group (p < 0.05). Diaphragm activation was lower in AIS patients during balance tasks (p < 0.01). Although no significant difference was observed in COP displacement between the groups, trunk inclination was significantly greater in the AIS group during certain tasks (p < 0.05). Conclusion These findings suggest distinct postural control patterns in AIS patients, highlighting the importance of targeted interventions to improve balance and core muscle function in this population.

Objective:To study the relationship between the polarization state of hippocampal microglia and depression-like behavior in mice and the regulatory effect of Xiaoyaosan.Methods:Sixty female BALB/C mice were randomly divided into control group, model group, Xiaoyaosan group and fluoxetine group according to the random number method with 15 in each group. Except for control group, the mice in the other 3 groups received chronic restraint stress for 21 days to establish the depressive model. The mice in the Xiaoyaosan group and fluoxetine group were gavaged with Xiaoyaosan(28.06 g/kg) and fluoxetine(3.03 mg/kg) respectively, while the mice in control and model groups received the same volume of 0.9% NaCl solution. Mouse behaviors were evaluated by sucrose preference test and elevated plus maze test.ELISA was used to detect the contents of 5-hydroxytryptamine(5-HT), dopamine(DA) in serum and transforming growth factor-β1(TGF-β1), interleukin-10(IL-10), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in the hippocampus. Immunohistochemistry was used to detect inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1) expression.Western blot was used to detect the protein levels of iNOS, Arg-1, CD86 and CD206. The mRNA expression of iNOS and Arg-1 in hippocampus was detected by qRT-PCR. The pathological changes of hippocampus were observed by HE staining.SPSS 27.0 software was used to analyze the data. One-way ANOVA was used for comparison among multiple groups, and LSD test was used for pairwise comparison.Results:(1) There were significant differences in sucrose preference among the 4 groups ( F=46.62, P<0.05).The sucrose preference of model group was lower than that of the control group ( P<0.05), while the sucrose preference of Xiaoyaosan group was higher than that of the model group ( P<0.05).There were significant differences in the number of open arm entries and residence time in the elevated plus maze test among the 4 groups ( F=24.63, 26.94, both P<0.05). The number of open arm entries and residence time in model group ((1.80±1.48)times, (6.19±1.67)s) were lower than those of the control group ((9.80±1.64)times, (56.81±2.75)s)) (both P<0.05). The number of open arm entries and residence time in Xiaoyaosan group ((6.80±0.84)times, (29.59±7.72)s) were significantly higher than model group(both P<0.05).(2) There were significant differences in serum 5-HT and DA levels among the 4 groups ( F=33.27, 76.03, both P<0.05). The serum 5-HT and DA levels in the model group were lower than those of the control group (both P<0.05).The serum 5-HT and DA levels in the Xiaoyaosan group were higher than those of model group (both P<0.05).(3)There were significant differences in the contents of TGF-β1, IL-10, TNF-α and IL-6 in the hippocampus of 4 groups ( F=31.93, 64.01, 25.74, 28.14, all P<0.05). The contents of TGF-β1 and IL-10 in the model group were lower than those of the control group, while the contents of TNF-α and IL-6 were higher (all P<0.05). Compared with the model group, the contents of TGF-β1 and IL-10 in Xiaoyaosan group ( TGF-β1: (30.40±1.56)pg/mL vs (23.77±2.24) pg/mL; IL-10: ((233.94±11.38)pg/mL) vs (130.46±15.34) pg/mL) were higher, and the contents of TNF-α ((73.35±1.51)ng/mL vs (85.89±4.52)pg/mL) and IL-6 (66.15±2.96)pg/mL vs (76.01±1.59)pg/mL) )were lower (all P<0.05).(4)The results of qRT-PCR, immunohistochemistry and Western blot all showed that there were significant differences in mRNA and protein levels of iNOS ( F=41.92, 20.78, 9.27, all P<0.05) and Arg-1 ( F=27.24, 24.23, 6.49, all P<0.05) in the hippocampus among the 4 groups of mice. The mRNA and protein levels of iNOS of the model group were higher than those in the control group (both P<0.05), while the mRNA and protein levels of Arg-1 were lower than those in the control group(both P<0.05).The mRNA and protein levels of iNOS in the Xiaoyaosan group were lower than those in the model group (both P<0.05), while the mRNA and protein levels of Arg-1 were higher than model group(both P<0.05).(5) The expressions of CD206 and CD86 in hippocampus of the 4 groups were significantly different ( F=86.14, 24.02, both P<0.05). Compared with the control group, the model group had a higher expression of CD86 in the hippocampus and a lower expression of CD206 (both P<0.05).Compared with the model group, the CD86 of Xiaoyaosan group was lower, while CD206 was higher (both P<0.05). (6) The HE staining results showed that the cells in the hippocampal CA1 region of the model group mice exhibited disordered arrangement, fewer cells, larger intercellular space, unclear boundary and other changes.The morphology of the cells in the Xiaoyaosan group was improved compared to the model group. Conclusion:Xiaoyaosan can inhibit M1 activation of microglia and neuronal damage in the hippocampus of mice caused by chronic restraint stress, exerting neuroprotective effects and improving depressive behavior in mice.

Abnormal expression of CMTM4 protein is closely related to tumour occurrence,development and prognosis.Although the important role of CMTM4 in tumours has been gradually manifested,its spe-cific mechanism of action in cervical cancer remains unclear.The aim of this study was to investigate the relationship between CMTM4 expression and clinicopathological features in cervical cancer and study its mechanism.Immunohistochemistry and Western blot were used to detect the expression level of CMTM4 in cancer tissues and paracancerous tissues,and it was found that CMTM4 was significantly under-ex-pressed in cervical cancer tissues(P＜0.001).The chi-square test analysed the relationship between high and low CMTM4 expression and the clinical and pathological characteristics of cervical cancer pa-tients and results found that CMTM4 expression was correlated with the number of births,HPV infection status,pathological type,FIGO stage and lymph node metastasis.Data from Western blot and RT-qPCR found that CMTM4 protein and mRNA levels in HaCaT cells were significantly higher than that of C-33A cells,HeLa cells,U14 cells,and HT-3 cells.Among them,the most significant change in CMTM4 ex-pression was observed in C-33A cells,so the C-33A cell line was selected for subsequent overexpression experiments.CCK-8 analysis found that the proliferation ability of C-33A cervical cancer cells in the pcDNA-CMTM4 group was significantly lower than that in the pcDNA-NC group(P＜0.001).Flow cy-tometry and Western blot results indicated that CMTM4 overexpression promoted apoptosis(P＜0.001),significantly increased Bax(P＜0.001)and cleaved caspase 3(P＜0.05)protein levels,and significant-ly decreased Bcl-2 protein level(P＜0.01).Western blot results further found that CMTM4 overexpres-sion significantly reduced the protein levels of p-PI3K(P＜0.001)and p-AKT(P＜0.01),but did not affect the protein levels of PI3K and AKT(P＞0.05).The above findings indicated that CMTM4 gene expression was down-regulated in cervical cancer,and CMTM4 overexpression inhibited cervical cancer cell proliferation and induced apoptosis by inhibiting the PI3K/AKT pathway.Therefore,CMTM4 may be used as a biological marker for screening cervical cancer.

Objective To investigate the possible association between cross-domain associative memory(AM)impairment and hippocampal subfield volumes in patients with schizophrenia(SCZ).Methods We enrolled 28 SCZ patients from Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,and 28 healthy controls(HCs)between 2019 and 2021.Based on an innovative AM paradigm and automated segmentation,3D-T1 weighted data of the objects were processed with PhiPipe and FreeSurfer.Differences in subfield volums between the two groups were analyzed using ANCOVA,while their relationship with AM scores was assessed using Pearson correlation.Results SCZ patients exhibited significantly poorer AM performance across three conditions compared with HCs.Marginally significant reductions were observed in the total volume of bilateral hippocampus,encompassing both the hippocampal head and body.Significant volume reductions were identified in the bilateral presubiculum and parasubiculum.The volumes of bilateral presubiculum head(r=0.273,P=0.042),parasubiculum(r=0.397,P=0.002),and CA1 head(r=0.382,P=0.004)exhibited positive correlations with cross-domain AM performance.Conclusion The bilateral presubiculum and parasubiculum,as hippocampal subregions significantly associated with cross-modal AM deficits in SCZ,may play a crucial role in the pathology of AM.