ObjectiveTo investigate whether the expression of Piezo1 in bulbar conjunctival fibroblasts contributes to the development of conjunctivochalasis （CCH）. MethodsPrimary bulbar conjunctival fibroblasts were obtained from CCH patients and normal control （NC） group by tissue block applanation. The cells were then purified and subjected to fibroblast identification. Immunohistochemical analysis was performed to assess Piezo1 expression in the bulbar conjunctival tissue of the NC and CCH groups. Immunofluorescence was used to detect the expression of Piezo1 in bulbar conjunctival fibroblasts in the CCH and NC groups， as well as the expression of matrix metalloproteinase-9（MMP-9） after the intervention of the Piezo1 agonist， Yoda1. qRT-PCR was used to detect the expression of mRNA of Piezo1 and MMP-9 in the CCH and NC groups， as well as the expression of mRNA of MMP-9 after the intervention of Yoda1. In addition， confocal microscopy was used to detect Ca²⁺influx in bulbar conjunctival fibroblasts in the NC group after Yoda1 intervention. Membrane clamp was used to detect the current amplitude of NC bulbar conjunctival fibroblasts after Yoda1 intervention to verify the functional expression of Piezo1. ResultsPrimary bulbar conjunctival fibroblasts were successfully cultured. Immunohistochemical analysis revealed elevated Piezo1 protein expression in the CCH group （P<0.01）. qRT-PCR analysis showed that Piezo1 mRNA expression was higher in the CCH group than in the NC group （P<0.01）， as was MMP-9 mRNA expression （P<0.01）. Furthermore， MMP-9 mRNA expression was higher in the CCH+Yoda1 group than in the CCH group （P<0.01）. Immunofluorescence staining for Piezo1 revealed enhanced fluorescence on the cell membranes of the CCH group compared with the NC group （P<0.05）， and the fluorescence of MMP-9 was enhanced by the addition of Yoda1 stimulation compared with that of the CCH group （P<0.05）. Confocal microscopy of NC group bulbar conjunctival fibroblasts after the addition of Yoda1 showed enhanced fluorescence of Piezo1 （P<0.05）. The addition of Yoda1 activated enhanced current amplitude， showed by membrane clamp detection of NC group bulbar conjunctival fibroblasts （P<0.000 1）. ConclusionMechanical damage produced by conjunctival tissues in conjunctivochalasis upregulates Piezo1 expression， and Piezo1 activation may amplify the mechanical damage caused by CCH.

Objective: To explore the relationship between life skills, psychological resilience and subjective well-being among primary and secondary school students, so as to provide evidence for targeted adolescent mental health education. Methods: From September to November, 2025, a total of 5 831 primary and secondary school students from five cities (Beijing, Guangzhou, Shenzhen, Chongqing, Urumqi) were selected by convenience sampling. The Adolescent Subjective Well being Scale, School based Adolescents Life Skills Scale, and Adolescent Psychological Resilience Scale were used for investigation. Data were analyzed using t-tests, one way ANOVA, and linear regression. Results: The total mean score of students subjective well being was (5.46± 0.91) ; the total mean score of life skills was (3.69±0.64); the total mean score of psychological resilience was (3.66±0.69). Statistically significant differences in subjective well being scores were found among students grouped by gender, grade, school stage, residential city, living with parents or living with siblings ( t/F =4.14, 53.92, 14.53, 49.99, 13.49, 2.18, all P <0.01). Stratified regression analyses were performed by gender (adjusting for school stage, residential city and living arrangement) and by school stage (adjusting for gender, residential city and living arrangement), the regression results indicated that life skills of boys, girls, primary school students and junior high school students( β =0.54, 0.53, 0.50, 0.57) and their psychological resilience ( β = 0.56 , 0.60, 0.56, 0.60) were positively associated with subjective well being (all P <0.01). Conclusions Life skills and psychological resilience may be important protective factors for subjective well being among primary and secondary school students. School based mental health education should emphasize life skills training and resilience building to promote students subjective well being.

Objective: To explore the association between parental subjective well-being and subjective well-being among primary and secondary school students, so as to provide evidence for promoting adolescent mental health from a family perspective. Methods: From September to November 2025, a convenience sampling method was used to recruit 4 612 students in grades 4-8 from 12 primary and secondary schools in five cities—Beijing, Guangzhou, Shenzhen, Chongqing, and Urumqi—along with their parents. Students completed the Adolescent Well being Survey Questionnaire, while parents completed the Parental Well being Survey Questionnaire. Data were analyzed using t-test, one way analysis of variance, multiple linear regression, Logistic regression, and stratified subgroup analyses. Results: The maximum score of the subjective well-being scale for primary and secondary school students was 301, with a total score of (224.07±46.63), representing 74.4% of the full score; the maximum score of the parental subjective well-being scale was 120, with a total score of (92.35±15.10), representing 77.0%. Multiple linear regression analysis showed that parental subjective well-being was positively associated with students overall subjective well-being, positive affect, and satisfaction in each domain (friendship, family, school, environment, freedom, and academics), and negatively associated with negative affect ( β =0.45, 0.08, 0.06, 0.07, 0.05, 0.04, 0.05, 0.04, -0.05, all P <0.01). Logistic regression and stratified analysis showed that parental subjective well-being was positively associated with students high subjective well-being ( OR =1.03), and the association existed in subgroups of different gender, grade and family structure ( OR =1.02-1.04) (all P <0.05). Conclusions Parental subjective well-being is positively associated with students subjective well-being. Future interventions should incorporate an integrated strategy featuring family-school collaboration to promote adolescent well-being.

Objective The aim of the study is to analyze the incidence patterns and epidemiological characteristics of parasitic and vector-borne diseases in the Minhang and Jinshan districts of Shanghai, and provide evidence-based information for optimizing prevention and control measures. Methods We collected information from epidemic reports and epidemiological investigation forms for cases of parasitic and vector-borne diseases from 2005 to 2024 in Shanghai's Minhang and Jinshan districts. Descriptive epidemiological method were adopted to conduct a comparative analysis of incidence trends, epidemic characteristics, and infection sources. Results A total of 229 cases in 7 categories were reported between 2005 and 2024, with an average annual incidence rate of 0.36/100 000. The average annual incidence rate in Minhang District was significantly higher than that in Jinshan District. The most prevalent diseases were malaria and dengue fever, followed by Japanese encephalitis. Monthly case reports were available, predominantly from June to October, with a peak in July-August. A statistically significant difference was observed between the two districts in case distribution during June-October (P＜0.001), whereas no significant difference was found for July-August (P=0.331). The majority of cases were young men (111/229,48.47%), aged 20-39 years. Migrant workers/farmers constituted the largest occupational group (55/229, 24.02%). Registered residents of other provinces and cities (147/229,64.19%), and the main source of infection was overseas importation (112/229,48.91%). There were no statistically significant differences in gender and household-registration composition between the two districts (P＞0.05). Significant differences existed in age, occupation, and source of infection (P＜0.05). The imported diseases were malaria and dengue fever, with Africa and Southeast Asia being the primary source locations. Malaria was the predominant disease imported from other provinces and cities, with cases having been imported from abroad since 2012. Local infections were mainly Japanese encephalitis, followed by malaria (with the last local case reported in 2010). Cases between 2005 and 2009 were predominantly imported from other provinces and cities. The proportion of cases imported from abroad increased sharply after 2010, particularly in Minhang District. Local infections sometimes arise in Jinshan District, with Japanese encephalitis serving as the primary type. Conclusions Incidence rates of parasitic and vector-borne diseases in Minhang and Jinshan districts have generally remained low. To further reduce this disease burden, it will be necessary to strengthen joint measures for prevention and control, eliminate the environmental risk factors of vector organisms, enhance monitoring and precise control of the environment and inbound personnel to prevent the occurrence and transmission of parasitic and vector-borne diseases.

Piezo1, a mechanosensitive nonselective cation channel characterized by multiple transmembrane domains, plays a critical role intransducing mechanical stimuli at the cellular membrane and participates in various physiological and pathological processes. Recent studies have established a significant association between Piezo1 and the occurrence and development of multiple ophthalmic disorders. Substantial evidence demonstrates that Piezo1 contributes to ocular disease progression by regulating fundamental cellular processes including proliferation, differentiation, apoptosis, and inflammatory responses, with particular relevance to glaucoma, corneal diseases, retinal disorders, and dry eye syndrome. Piezo1 has made rapid progress in ophthalmology, and has been established as an important mechanosensor in the eye, widely involved in intraocular pressure regulation, retinal function maintenance, corneal homeostasis and repair, and ocular development, and its dysfunction is closely related to the pathological mechanisms of many important blinding eye diseases. Consequently, Piezo1 is not only a key molecule for understanding ocular mechanobiology, but also represents a highly promising therapeutic target. Its study offers new perspectives for the development of novel therapeutic strategies against ocular diseases. This review systematically summarizes current research advances regarding Piezo1 channels in ophthalmology, analyzes their mechanistic involvement in disease processes, and evaluates their potential therapeutic value, thereby offering innovative perspectives for the clinical management of ocular diseases.

BACKGROUND: The use of potentially inappropriate medications (PIMs) is a major concern for medication safety as it may entail more harm than potential benefits for older adults. This study aimed to explore the prescribing rate, healthcare utilization, and expenditure of older adults using PIMs in China. METHODS: A cross-sectional analysis was conducted using a national representative database of all medical insurance beneficiaries across China, extracting ambulatory visit records of adults aged 65 years and above between 2015 and 2017. Descriptive analysis was conducted to measure the rate of patients exposed to PIM, prescribing rate of each PIM, average annual outpatient visits per patient, average total medication costs for each visit, average annual cost of PIMs for each patient, and average annual medication costs for each patient. Generalized linear model with logit link function and binomial distribution was used to examine the adjusted associations between PIMs and independent variables. RESULTS: In total, 845,278 (33.2%) participants were identified to be exposed to at least one PIM. Patients aged 75-84 years (38.1%, 969,809/2,545,430) and ≥85 years (37.9%, 964,718/2,545,430) were more likely to be prescribed with PIMs. Beneficiaries of the Urban Employee Basic Medical Insurance (UEBMI) and living in eastern and southern regions were more frequently prescribed with PIMs. Compared with patients without PIM exposure (7.5 visits, drug cost of RMB 1545.0 Yuan), patients with PIM exposure showed higher adjusted average annual number of outpatient visits (10.7 visits, β = 3.228, 95% confidence interval [CI] = 3.196-3.261) and higher annual drug costs (RMB 2461.8 Yuan, Coef. = 916.864, 95% CI = RMB 906.292-927.436 Yuan). CONCLUSIONS The results showed that the use of PIM among older adults was common in China. This study suggests that the use of PIM could be considered as a clear target, pending multidimensional efforts, to promote rational prescribing for older adults.
Humans ; Aged ; Cross-Sectional Studies ; Aged, 80 and over ; Male ; Female ; China ; Inappropriate Prescribing/economics* ; Patient Acceptance of Health Care/statistics & numerical data* ; Potentially Inappropriate Medication List/statistics & numerical data* ; Health Expenditures/statistics & numerical data*

Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a spectrum of liver injuries, including steatosis to steatohepatitis (MASH), liver fibrosis, cirrhosis, and relevant complications. The liver mainly comprises hepatocytes, liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs), immune cells (T cells, B cells), and hepatic stellate cells (HSCs). Crosstalk among these different liver cells, endogenous aberrant glycolipid metabolism, and altered gut dysbiosis are involved in the pathophysiology of MASLD. This review systematically examines advances in understanding the molecular pathogenesis of MASLD, with a focus on emerging therapeutic targets and translational clinical trials. We first delineate the crucial regulatory mechanisms involving diverse liver cells and the gut-liver axis in MASLD development. These cell-specific pathogenic insights offer valuable perspectives for advancing precision medicine approaches in MASLD treatment. Furthermore, we evaluate potential therapeutic targets and summarize clinical trials currently underway. By comprehensively updating the MASLD pathophysiology and identifying promising strategies, this review aims to facilitate the development of novel pharmacotherapies for this increasingly prevalent condition.
Humans ; Fatty Liver/therapy* ; Animals ; Liver/pathology* ; Kupffer Cells/metabolism* ; Hepatocytes/metabolism* ; Hepatic Stellate Cells/metabolism*

To study the ameliorative effect of Eucommiae Cortex extract on spatial learning disabilities in APP/PS1 double-transgenic mice and explore its relationship with estrogen receptor β(ERβ)/c-Jun N-terminal kinase(JNK) signaling pathway, sixty 3-month-old male APP/PS1 mice were randomly divided into a model group, an anti-brain failure capsule group(0.585 g·kg~(-1)), a donepezil hydrochloride group(0.65 mg·kg~(-1)), and a Eucommiae Cortex extract group(1.3 g·kg~(-1)), and 15 C57BL/6 mice of the same genetic background were set as WT control group. The learning and memory ability of mice was assessed by the Morris water maze test(MWM), the passive avoidance test(PAT), and the novel object recognition test(NOR). The histomorphological and cellular ultrastructural features of the hippocampal region of the mice were observed by hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM); the molecular docking validation of the key active ingredients and the key targets was performed by using AutoDock Vina software, and the immunohistochemical method(IHC) was used to detect the ERβ expression in the dentate gyrus(DG) area of mouse hippocampus. Western blot(WB) was utilized to detect the expression of ERβ, p-JNK, and JNK in mouse hippocampal area. Compared with those in the WT control group, the results of behavioral experiments showed that the latency of the mice in the model group was significantly increased, the number of platform traversals, and the target quadrant residence time were significantly decreased in the MWM. The evasion latency was significantly reduced, and the number of errors was significantly increased in the PAT. The index of recognition of novel objects was significantly reduced in the NOR. The results of HE staining indicated that the hippocampal area of mice in the model group showed a decrease in the number of neurons, disorganization of pyramidal cell arrangement, nucleus consolidation, and other changes. TEM results showed that some neuronal nuclei in the hippocampal area had a consolidated state, slightly thickened and aberrant nuclear membranes, and fewer intracytoplasmic nidus bodies; the IHC results showed that the expression of ERβ in the hippocampal DG area of the mice was reduced. The WB results showed that the ERβ expression in the hippocampal tissue was decreased, and the p-JNK/JNK level was elevated. Compared with the model group, the Eucommiae Cortex extract group showed a significant decrease in latency, and increase in number of platform traversals and target quadrant residence time in the MWM, a significant increase in evasion latency and decrease in number of errors in the PAT, and a significant increase in the index of recognition of novel objects in the NOR. In addition, there was an increase in the number of neurons in the hippocampal area of mice. The pyramidal cells tended to be arranged in an orderly manner; the nuclei of neurons in the hippocampal area were in a better state; the expression of ERβ in the hippocampal DG area of the mice was elevated; the expression of ERβ in the hippocampal tissue was elevated, and the level of p-JNK/JNK was reduced. The effects of donepezil hydrochloride group and anti-brain failure capsule on APP/PS1 mice in terms of behavioral, HE, and TEM indexes were similar to those of Eucommiae Cortex extract, and there was no significant difference between donepezil hydrochloride group and the model group in IHC and WB experiments, and the results of molecular docking indicated that the estrogen-like components in Eucommiae Cortex extract were tightly bound to ERβ. In conclusion, the binding of Eucommiae Cortex extract to estrogen receptors, regulation of ERβ expression, and activation of ERβ/JNK signaling pathway may be one of the key mechanisms by which it improves the learning and memory ability of APP/PS1 mice.
Animals ; Male ; Mice ; Mice, Transgenic ; Memory/drug effects* ; Mice, Inbred C57BL ; Estrogen Receptor beta/genetics* ; Eucommiaceae/chemistry* ; Alzheimer Disease/psychology* ; Amyloid beta-Protein Precursor/metabolism* ; Presenilin-1/metabolism* ; Humans ; MAP Kinase Signaling System/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Hippocampus/metabolism* ; Maze Learning/drug effects* ; Learning/drug effects*

This study aims to investigate the optimal ratio of Astragali Radix-Curcumae Rhizoma(AC) for inhibiting the proliferation of 143B osteosarcoma cells, and to investigate the mechanism by which AC inhibits osteosarcoma growth and metastasis through angiogenesis and cell adhesion mediated by the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/hypoxia inducible factor-1α(HIF-1α) pathway. A subcutaneous 143B tumor-bearing nude mouse model was successfully established and randomly divided into the model group, and the AC 1∶1, 2∶1, and 4∶1 groups. Body weight, tumor volume, and tumor weight were recorded. Real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot were used to detect the mRNA and protein expression levels of PI3K, Akt, phosphorylated Akt(p-Akt), HIF-1α, vascular endothelial growth factor A(VEGFA), transforming growth factor-β1(TGF-β1), epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), vimentin, matrix metalloproteinase 2(MMP2), matrix metalloproteinase 9(MMP9), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and caspase-3 in the hypoxic core region of the tumor tissue. A cell hypoxia model was established, and the effects of AC-medicated serum(model group, AC 1∶1, 2∶1, and 4∶1 groups) on angiogenesis, proliferation, adhesion, invasion, and migration of 143B osteosarcoma cells were examined through CCK-8, flow cytometry, Transwell assay, cell adhesion assay, and HUVEC tube formation assay. The results showed that compared with the model group, the tumor weight and volume were smallest in the 2∶1 group. The expression levels of PI3K, Akt, p-Akt, HIF-1α, VEGFA, and TGF-β1 were significantly decreased, and the protein expression of E-cadherin was significantly increased, while the protein expression of N-cadherin, vimentin, MMP2, and MMP9 was significantly decreased. Additionally, the protein expression of Bax and caspase-3 was significantly increased, and Bcl-2 protein expression was significantly decreased. In vitro experiments showed that after intervention with AC-medicated serum at a 2∶1 ratio, the cell activity, adhesion, invasion, and migration of 143B cells were significantly reduced, apoptosis was significantly increased, and HUVEC tube formation was significantly decreased. In conclusion, the 2∶1 ratio of AC showed the most effective inhibition of 143B cell growth. AC can inhibit the growth and metastasis of osteosarcoma 143B cells by regulating the PI3K/Akt/HIF-1α signaling pathway, inhibiting angiogenesis and reducing cell adhesion, invasion, and migration.
Osteosarcoma/pathology* ; Animals ; Proto-Oncogene Proteins c-akt/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Humans ; Mice ; Cell Adhesion/drug effects* ; Cell Proliferation/drug effects* ; Neovascularization, Pathologic/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Phosphatidylinositol 3-Kinases/genetics* ; Cell Line, Tumor ; Mice, Nude ; Signal Transduction/drug effects* ; Astragalus Plant/chemistry* ; Bone Neoplasms/physiopathology* ; Male ; Rhizome/chemistry* ; Mice, Inbred BALB C ; Angiogenesis

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