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.

A scoping review was performed to systematically search and summarize the clinical research in the treatment of dysmenorrhea with oral Chinese patent medicines. The oral Chinese patent medicines for treating dysmenorrhea in three major drug lists, guidelines, and textbooks were screened, and the relevant clinical trials were retrieved from eight Chinese and English databases. The key information of the included trials was extracted and visually analyzed. A total of 50 Chinese patent medicines were included, among which oral Chinese patent medicines for the dysmenorrhea patients with the syndrome of Qi stagnation and blood stasis accounted for the highest proportion, and the average daily cost varied greatly among Chinese patent medicines. A total of 150 articles were included, involving 22 Chinese patent medicines, among which Guizhi Fuling Capsules/Pills, Sanjie Zhentong Capsules, and Dan'e Fukang Soft Extract were the most frequently studied. These articles mainly reported randomized controlled trial(RCT), which mainly focused on the comparison of the intervention effect between Chinese patent medicines combined with western medicine and western medicine alone, and the sample size was generally 51-100 cases. The high-frequency outcome indicators belonged to nine domains such as effective rate, adverse reactions, and laboratory examinations. This study showed that oral Chinese patent medicines had advantages in the treatment of dysmenorrhea, and the annual number of related clinical trials showed an overall growing trend. However, there were still problems such as insufficient safety information and vague description of traditional Chinese medicine(TCM) syndromes types in the instructions of Chinese patent medicines. The available clinical research had shortcomings such as uneven distribution of Chinese patent medicines, limited research scale, poor methodological rigor, and insufficient standardization of outcome indicators. In the future, it is necessary to deepen the development of high-quality clinical research and improve the contents of the instructions to ensure the effectiveness and safety of the clinical application of oral Chinese patent medicines in the treatment of dysmenorrhea.
Dysmenorrhea/drug therapy* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Female ; Administration, Oral ; Nonprescription Drugs/administration & dosage*

Basket trial, as an innovative clinical trial design concept, marks the transformation of medical research from the traditional large-scale and single-disease treatment to the precise and individualized treatment. By gradually incorporating the Bayesian method during development, the trial design becomes more scientific and reasonable and increases its efficiency. The fundamental principle of the Bayesian method is the utilization of prior knowledge in conjunction with new observational data to dynamically update the posterior probability. This flexibility enhances the basket trial's capacity to effectively adapt to variations during the research process. Consequently, it enables researchers to dynamically adjust research strategies based on accumulated data and improve the predictive accuracy regarding treatment responses. In addition, the design concept of the basket trial aligns with the traditional Chinese medicine(TCM) principle of "homotherapy for heteropathy". The principle of "homotherapy for heteropathy" emphasizes that under certain conditions, different diseases may have the same treatment. Similarly, basket trials allow using a uniform trial design across multiple diseases, offering enhanced operational and significant practical value in the realm of TCM, particularly within the context of syndrome-based disease research. By introducing basket trials, the design of TCM clinical studies will be more scientific and yield higher-quality evidence. This study systematically categorized various Bayesian methods and models utilized in basket trials, evaluated their strengths and weaknesses, and identified their appropriate application contexts, so as to offer a practical guide for designing basket trials in the realm of TCM.
Bayes Theorem ; Humans ; Medicine, Chinese Traditional/methods* ; Research Design ; Clinical Trials as Topic/methods* ; Drugs, Chinese Herbal/therapeutic use*

Cryopreservation is the primary technique for in vitro preservation of allogeneic tissue. However, its success is often hindered by factors such as low temperature, ischemia, and hypoxia. This study investigated the potential of Sini Decoction, known for its antioxidant and anti-apoptotic properties, to reduce cryopreservation-induced injury in rats' sciatic nerves. Sini Decoction was prepared according to the Chinese Pharmacopoeia, and its cytotoxicity on Rsc96 cells was assessed by using the CCK-8 method. Sini Decoction at concentrations of 4, 8, and 16 mg·mL~(-1), termed as low-(SL), medium-(SM), and high-(SH) doses group, was used for cryopreservation of rats' sciatic nerves. A normal control(NC) group and a fresh nerve control(fresh) group were set. Flow cytometry and TUNEL staining were used to detect the apoptosis of neural tissue cells after cryopreservation. Western blot was used to detect the expression of apoptosis-related proteins(Bcl-2, Bax, caspase-3, and caspase-8) and nerve regeneration proteins(NGF and BDNF) in vitro after cryopreservation. Oxidative damage of neural tissue after cryopreservation was evaluated by measuring levels of GSH, SOD, MDA, ROS, and ATP. Cryopreserved nerves were then used for allogeneic transplantation. One week after transplantation, CD4~+ and CD8~+ fluorescent double staining assessed inflammatory cell invasion in the transplanted nerve segment, and ELISA evaluated the expression of serum inflammatory factors(IL-1, IFN-γ, and TNF-α) in recipients. Twenty weeks after transplantation, electrophysiology and NF200 neurofilament staining were used to evaluate nerve regeneration. RESULTS:: showed that Sini Decoction at concentrations of below 32 mg·mL~(-1) exhibited no cytotoxicity to Rsc96 cells. During in vitro nerve cryopreservation, Sini Decoction significantly reduced cell apoptosis, ROS, and MDA production compared to the NC group. In the SH group, the protein expression of NGF and BDNF in vitro, as well as ATP, SOD, and GSH production, were significantly increased. In the rejection reaction one week after transplantation, compared to the fresh nerve transplantation group, the SL and SM groups showed reduced CD4~+ and CD8~+ T cell invasion in the transplanted nerve segment and down-regulated IL-1, IFN-γ, and TNF-α expression in recipient serum. Twenty weeks after transplantation, the electrophysiological test results of CMAP, NCV, and NF200 neurofilament protein fluorescent staining in the SM and SH groups were superior to those in the NC and fresh groups. These findings indicate that Sini Decoction offers protective benefits in the cryopreservation of rats' sciatic nerves and holds significant potential for the in vitro preservation of tissue and organs.
Animals ; Apoptosis/drug effects* ; Rats ; Oxidative Stress/drug effects* ; Sciatic Nerve/cytology* ; Cryopreservation ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Protective Agents/pharmacology*

Objective To investigate the potential therapeutic effects,targets,and pathways of wogonoside in hypertension-induced renal injury using the Gene Expression Omnibus(GEO)database and network pharmacology,and to validate the effects of wogonoside intervention on the renal tissues of spontaneously hypertensive rats(SHR),angiotensin Ⅱ(Ang Ⅱ)-stimulated NRK-52E cell apoptosis,and the regulation of relevant pathways through in vivo and in vitro experiments.Methods GEO dataset and network pharmacology analyses were performed to investigate the key therapeutic targets of wogonoside for hypertensive nephropathy.The STRING database was used to analyze protein-protein interactions.Biological functions were annotated via Gene Ontology(GO),and the potential signaling pathways were enriched using the Kyoto Encyclopedia of Genes and Genomes(KEGG).SHR were randomly divided into groups and given low,medium,or high doses of wogonoside(0.075,0.75,and 7.5 mg/kg)via gastric gavage for 10 weeks.Morphological changes in the kidney tissue were assessed by hematoxylin-eosin(HE)staining.Serum levels of inflammatory cytokines,including tumor necrosis factor α(TNF-α),interleukin(IL)-1 β,and IL-6,were measured using ELISA.Apoptosis rates were evaluated by TUNEL staining,and Western blot was performed to determine the expression of Bax,Bcl-2,cleaved caspase-3,and caspase-3,and the expression of phosphorylated and total extracellular signal-regulated kinases(ERK)and p38 mitogen-activated protein kinase(MAPK)proteins.An in vitro model of Ang Ⅱ-stimulated NRK-52E cells was constructed and was treated with wogonoside at different concentrations(25,50,or 100 μmol/L)for 24 h.The apoptosis rates were then assessed by Annexin V staining,and Western blot was performed to validate the expression of apoptosis-related and pathway-associated proteins.Results Analysis of dataset GSE41453 revealed 11673 upregulated and 5902 downregulated genes in the renal tissues of SHR compared to the Wistar Kyoto(WKY)rats,or the WKY control group.Through the analysis of multiple databases,371 potential targets of wogonoside were identified,resulting in 98 overlapping targets.From these,45 core therapeutic targets were identified through further analysis,including TNF,CASP3,etc.GO analysis significantly enriched processes such as the negative regulation of apoptosis.KEGG pathway enrichment analysis highlighted the apoptosis pathway,IL-17 signaling pathway,and MAPK signaling pathway as being significantly enriched.Wogonoside treatment effectively mitigated pathological damage in SHR kidney tissues and significantly inhibited the expression of inflammatory cytokines,including TNF-α,IL-1 β,and IL-6(P＜0.05).It also decreased cell apoptosis rates in SHR kidney tissues and Ang Ⅱ-stimulated NRK-52E cells,downregulated the expression of Bax and cleaved caspase-3,and upregulated Bcl-2 expression(P＜0.05).Furthermore,wogonoside treatment inhibited the phosphorylation of ERK and p38 MAPK in SHR kidney tissues and Ang Ⅱ-stimulated NRK-52E cells(P＜0.05).Conclusion Wogonoside may exert its protective effects against hypertension-induced renal injury by suppressing the inflammatory response and cell apoptosis,potentially through the regulation of the MAPK signaling pathway.

Objective To investigate the potential therapeutic effects of trifolin on hypertension-induced renal injury,as well as the key targets and pathways involved.Methods The mRNA transcriptional profiles of peripheral blood clinical samples from hypertensive patients were analyzed using Gene Expression Omnibus(GEO),a high-throughput gene expression database.The network pharmacology method was employed to screen key targets of trifolin in treating hypertension-induced renal injury.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted.NRK-52E cells,a rat renal proximal tubular cell line,were used to construct an angiotensin Ⅱ(Ang Ⅱ)-stimulated cell model.Flow cytometry was performed to assess cell apoptosis rates and Western blotting was performed to determine the expression levels of apoptosis-related proteins,including Bax,Bcl-2,cleaved caspase-3,and caspase-3,and the phosphorylation and total protein levels of the key MAPK pathway proteins,including ERK,p38 MAPK,and JNK.Results Analysis of the dataset GSE75360 revealed that,compared with healthy controls,3 331 genes were upregulated and 3 197 genes were downregulated in peripheral blood mononuclear cells of hypertensive patients.According to network pharmacology analysis,472 potential targets of trifolin were identified,including CASP3 and MAPK1.Protein-protein interaction network analysis showed that these targets were closely associated with apoptosis regulatory signaling pathways.GO and KEGG pathway enrichment analyses indicated that trifolin was significantly enriched in pathways associated with negative regulation of apoptosis,apoptotic signaling pathways,and the MAPK signaling pathway.The in vitro experiments confirmed that,compared with the Ang Ⅱ group,trifolin intervention inhibited apoptosis in Ang Ⅱ-stimulated NRK-52E cells,suppressed the expression of Bax and cleaved caspase-3,promoted Bcl-2 expression,and inhibited the phosphorylation of p38 MAPK,ERK,and JNK(P<0.05).Conclusion Trifolin may exert its protective effect against hypertension-induced renal injury by inhibiting Ang Ⅱ-induced NRK-52E cell apoptosis and regulating the MAPK signaling pathway,representing an important mechanism underlying its therapeutic action.

Objective Understanding the population structure of mosquitoes in the drainage system of Minhang District,Shanghai,and exploring the physical prevention and control technology of mosquito traps with a Vazor mosquito repellent film in the drainage system.Methods A 500 mL water spoon was used to assist in visual inspection to investigate the breeding status of mosquito larvae in the drainage system.A carbon dioxide mosquito trap method was used to monitor adult mosquitoes around the ground drainage system,and the artificial hour method was used to monitor adult mosquitoes around the underground drainage system.Mosquito-repellent film was applied at a rate of 1 mL/m2 to the drainage system where mosquito larvae or pupae are found,and the breeding situation was observed and recorded.Results The positivity rate of mosquitoes breeding in the ground drainage system was 50%.The mosquito larvae in the drainage channels were primarily Aedes albopictus,whereas Ae.albopictus were primarily noted in the sewage wells.The proportions of Ae.albopictus and Culex pipiens pallens in the rainwater wells were similar,and the dominant mosquito species around the surface drainage system was Ae.Albopictus.The positive rate of mosquito breeding in the underground drainage system was 47%,with the dominant mosquito species being Cx.pipiens pallens(58.39%)followed by Ae.albopictus(41.6%).The dominant adult mosquito species around the drainage system were Cx.pipiens pallens(83%)followed by Ae.albopictus(11%).In terms of the effectiveness of mosquito-repellent water film,the mosquito breeding rates of the ground and underground drainage systems using mosquito-repellent water film decreased to 2.78%and 5%after 1 week of use,respectively,and then rebounded after the 3rd week.After a supplementary dose during the 5th week,the breeding rates returned to normal.No statistically significant differences were observed in the effect compared with the standard control group using 1%bisulfite granules;however,a statistically significant difference was noted compared with the blank control group without special treatment.Conclusions In the drainage system of Minhang District,Shanghai,mosquito breeding is severe,and variations exist in the dominant mosquito species in different environmental drainage facilities.The simultaneous use of mosquito-repellent films can effectively control mosquito breeding in drainage systems.

OBJECTIVE: Human brucellosis is a serious public health concern in the Xilingol League, Inner Mongolia; however, the epidemic trends are unclear. METHOD: In this study, Joinpoint regression analysis and spatiotemporal analysis were applied to investigate the epidemic evolution of human brucellosis. RESULT: From 2004 to 2023, a total of 35,747 cases were reported, with an annual average of 1787.35 cases and an annual average incidence rate of 176.04/100,000. The incidence increased from 173.96/100,000 in 2004 to 500.71/100,000 in 2009 and fluctuated to 61.43/100,000 in 2023. Three epidemic join points were observed in which the disease experienced an alternative rise and fall, peaking in 2009 (APC = 21.73, P > 0.001) and 2020 (APC = 21.51, P > 0.001). The disease showed a persistent decline trend in lentitude (AAPC = -5.30, P > 0.001), suggesting challenges in disease control and a higher risk of rebound. The most cases were reported in Xilinhot City ( n = 4,777), followed by 4,391 in Sonid Left Banner, and 4,324 in Abaga Banner. Spatiotemporal analysis revealed two high clusters (CI and CII) from 2005 to 2012, the high cluster encompassing eight counties and shifting from north to south. CONCLUSION The present analysis highlights that human brucellosis has decreased significantly in the Xilingol League, but the epidemic is still severe; further implementation of a strict control program is necessary.
China/epidemiology* ; Humans ; Brucellosis/epidemiology* ; Epidemics ; Spatio-Temporal Analysis ; Incidence ; Cluster Analysis

Human cytomegalovirus (HCMV) poses a significant risk of neural damage during pregnancy. As the most prevalent intrauterine infectious agent in low- and middle-income countries, HCMV disrupts the development of neural stem cells, leading to fetal malformations and abnormal structural and physiological functions in the fetal brain. This review summarizes the current understanding of how HCMV infection dysregulates the Wnt signaling pathway to induce fetal malformations and discusses current management strategies.
Humans ; Cytomegalovirus Infections/virology* ; Wnt Signaling Pathway ; Pregnancy ; Female ; Cytomegalovirus/physiology* ; Pregnancy Complications, Infectious/virology* ; Congenital Abnormalities/virology* ; Animals

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*