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.

Objective To investigate the levels of gross α and gross β activities in different water types within a 40-kilometer radius around the Zhangzhou Nuclear Power Plant prior to its operation. Methods In 2018, drinking water samples were collected from the area surrounding the nuclear power plant during both the wet and dry seasons, including source water, treated water, tap water, and well water. The gross α and gross β activity concentrations were measured using a low-background α/β counter, followed by statistical analysis. Results A total of 80 water samples from different sources around the Zhangzhou Nuclear Power Plant were collected. The average gross α and gross β activity concentrations during the wet season were (0.110 ± 0.036) Bq/L and (0.643 ± 0.028) Bq/L, respectively, while those during the dry season were (0.124 ± 0.032) Bq/L and (0.624 ± 0.026) Bq/L, respectively. There were no significant differences in the gross α and gross β activity concentrations between the wet and dry seasons for the overall sample set (P > 0.05). However, there were statistically significant differences in the gross α and gross β activity concentrations between the wet and dry seasons for source water and well water (Z_wet = −2.005, −2.123; Z_dry = −1.943, −3.090; P < 0.05). Conclusion The radioactivity levels in different water types within various ranges around the Zhangzhou Nuclear Power Plant before its operation were determined. The measured activity concentrations were at the same level as those from previous investigations in other regions of Fujian Province.

Hepatocellular carcinoma （HCC） is a malignant tumor with high incidence and mortality rates worldwide. Recent studies have shown that neutrophil extracellular traps （NETs） play an important role in the development， progression， and immune escape of HCC. NETs are released by neutrophils and mainly consist of DNA， histones， and antimicrobial molecules， and in addition to immune defense， they are also involved in the initiation， metastasis， and thrombosis of HCC. This article elaborates on the formation and regulatory mechanisms of NETs， explores their potential mechanisms in the initiation， metastasis， immune escape， and thrombosis of HCC， and discusses the prospect of NETs as a target for the diagnosis and treatment of HCC， in order to provide new ideas for the precise treatment of HCC in the future and promote the early diagnosis and effective treatment of HCC.

In recent years,the incidence and mortality of heatstroke have been increasing annually alongside global warming,with a marked rise in cases exhibiting atypical symptoms.To address the increasingly complex challenges in heatstroke prevention and treatment,Heatstroke Prevention and Treatment Research Center of Chinese PLA,Expert Group of Heatstroke Prevention and Treatment of Chinese PLA,and Chinese PLA Professional Committee of Critical Care Medicine have jointly developed this guideline(2025 edition).Utilizing the Grading of Recommendations Assessment,Development and Evaluation(GRADE)system,Appraisal of Guidelines for Research and Evaluation(AGREE)criteria,and Reporting Items for Practice Guidelines in Healthcare(RIGHT)standards,and based on the 2015 draft"Expert Consensus on the Standardized Diagnosis and Treatment of Heatstroke"and the 2019"Chinese Expert Consensus on the Diagnosis and Treatment of Heatstroke",this guideline has been crafted.This guideline provides 25 evidence-based recommendations to guide the prevention,treatment and research of heatstroke,which thoroughly covers 8 critical domains:clinical classification,pathophysiological mechanisms,clinical manifestations,diagnostic criteria,differential diagnosis,treatment protocols,rehabilitation and return to work,and prevention.

Objective In view of the potential threat of adverse drug reaction(ADR)to patients'health and the limitations of traditional monitoring methods,this study investigates the construction method of an ADR knowledge graph based on a knowledge-driven technology path to promote the intelligent upgrading of pharmacovigilance field.Methods In this study,an adverse drug reaction knowledge base was established,and the data within the knowledge base were preprocessed.The BERT-CRF model was utilized to identify and extract the relevant entities,relationships and attribute information,and knowledge alignment was carried out by combining the rule method and statistical method.The knowledge fusion data was stored in the Neo4j graph database to construct the knowledge graph.Results Based on the established knowledge base,this study explored the method of constructing knowledge graph of adverse drug reaction by knowledge-driven technology,laying the groundwork for data mining and the development of intelligent auxiliary system tools based on knowledge graph.Conclusions The study on the construction method of an ADR knowledge graph based on a knowledge-driven technology path provides a new perspective and technical path for the intelligent upgrading of pharmacovigilance field.It holds important theoretical and practical significance for improving drug safety,protecting patients'health,and promoting the healthy development of pharmaceutical industry.

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.

Cancer is the main cause of death,and drug therapy has greatly improved the effectiveness of anti-tumor treatment.However,there are problems such as high adverse reactions and the risk of developing drug resistance after long-term use.There is an urgent need to seek new drug targets.Human antigen R(HuR),as an RNA binding protein,promotes the whole process of tumor occurrence,development and metastasis through post transcriptional regulation of mRNA stability,and HuR is general-ly highly expressed in tumor tissue,making it a new target for an-ti-tumor therapy and a standard for prognosis evaluation.Tradi-tional Chinese medicine formulas and their various chemical components can inhibit tumor proliferation,induce tumor cell ap-optosis,inhibit angiogenesis,suppress immune escape,and re-verse tumor drug resistance by regulating HuR activity.This re-view summarizes the importance of HuR in regulation of tumor progression,as well as analyzes the mechanisms of the antitumor effects through active ingredients of Chinese medicine with the regulation of HuR.It is expected to provide new ideas for tumor therapy and guidance for the development of HuR-targeted anti-tumor drugs.

Aim To investigate the effect of long-chain non-coding RNA(lncRNA)GS1-124K5.4 targeting regulation of PRDX6 on proliferation,migration and in-vasion of lung squamous carcinoma(LUSC)cells and the underlying mechanism.Methods The expression level of lncRNA GS1-124K5.4 in lung cancer tissues and adjacent tissues of 60 patients with LUSC were de-termined by fluorescence in situ hybridization.The ex-pression level of lncRNA GS1-124K5.4 in human nor-mal lung cells and LUSC cells were determined by qRT-PCR.Two kinds of LUSC cells(NCI-H 1703,SK-MES-1)with highest expression level of lncRNA GS1-124K5.4 were selected for subsequent experi-ments.The distribution of lncRNA GS1-124K5.4 in cells was studied by fluorescence in situ hybridization and prokaryotic separation.The effect of knockdown of lncRNA GS1-124K5.4 on proliferation of NCI-H1703 and SK-MES-1 cells was studied by CCK-8 experiment and cell clone formation experiment;the effect of knockdown of lncRNA GS1-124K5.4 on migration of NCI-H1703 and SK-MES-1 cells was studied by cell scratch experiment and Transwell cell migration experi-ment;and the effect of knockdown of lncRNA GS1-124K5.4 on invasion of NCI-H1703 and SK-MES-1 cells was studied by Transwell invasion experiment.The protein to be bound by lncRNA GS1-124K5.4 was detected by RNA pull-down combined with mass spec-trometry and immune-precipitation.The effect of knockdown of lncRNA GS1-124K5.4 targeting PRDX6 on proliferation,migration and invasion of NCI-H1703 and SK-MES-1 cells was studied.Results(1)The fluorescence intensity of lncRNA GS1-124K5.4 in lung squamous cell carcinoma increased compared with that in adjacent tissues(P＜0.05),and the expression of lncRNA GS1-124K5.4 was related with lymph node metastasis and clinical stage(P＜0.05).(2)The ex-pression level of lncRNA GS1-124K5.4 in NCI-H1703,NCI-H520 and SK-MES-1 cells significantly increased(P＜0.05).(3)The result of fluorescence in situ hybridization experiment and nucleoplasm sepa-ration experiment showed that lncRNA GS1-124K5.4 was mainly distributed in cell nucleus.(4)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of lncRNA GS1-124K5.4 significantly decreased(P＜0.05).(5)PRDX6 protein to be bound to LncRNA GS1-124K5.4 was determined by RNA pull-down combined with mass spectrometry and immunoprecipitation.(6)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNA GS1-124K5.4 significantly increased(P＜0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of PRDX6 significantly decreased(P＜0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNAGS1-124K5.4 and knockdown of PRDX6 showed no signifi-cant change(P＞0.05).Conclusions LncRNA GS1-124K5.4 is highly expressed in lung squamous cell carcinoma,and it may promote the proliferation,migration and invasion of lung squamous carcinoma cells by targeting the expression of PRDX6 protein.

Objective:To analyze the current situation and hotspots of medication literacy research at home and abroad, and provide references for medication literacy research in China.Methods:The literature related to medication literacy in the Web of Science Core Collection Database, Scopus and China National Knowledge Infrastructure Database were retrieved (up to May 31, 2024). The CiteSpace software was used to analyze the number of published papers, countries, institutions, journals, authors and keywords, etc.Results:A total of 604 literature were included (361 in Chinese and 243 in English). The literature related to medication literacy were first seen in 2000, and the number grew slowly, which showed rapid growth after 2016, and reached a peak in 2023. The country with the largest number of published English literature was China (69 articles), followed by the United States (66 articles). The literature from the United States were cited 3 623 times, and those from China were cited 2 523 times. Central South University and the Third Xiangya Hospital of Central South University were tied for the first place in terms of the number of published articles as institutions (both 15 articles). The top 5 institutions in terms of the number of Chinese publications were Xiangya Third Hospital of Central South University, Central South University, Yanbian University, Affiliated Hospital of Yanbian University, and Tianjin Chest Hospital. The discipline with the largest number of published English literature was pharmacology/pharmacy (107 articles), followed by public environmental occupational health (88 articles) and general internal medicine (39 articles); the discipline with the largest number of Chinese published articles was clinical medicine (124 articles), followed by research on medical and health policies and regulations (56 articles), and medical education and marginal medical disciplines (34 articles). Keyword cluster analysis showed that the top 3 keywords in the English literature were medication errors, health education, and community pharmacy, while those in the Chinese literature were health literacy, self-management, and health education.Conclusions:Research on medication literacy has rapidly developed in recent years. China and the United States are the main countries for research related to medication literacy. Health education and medication errors are the mainstream of the research. Future research can focus on personalized assessment and intervention measures of medication literacy, so as to develop high-quality assessment tools for medication literacy.