AIM:To analyze differential proteins associated with the pathogenesis of dry eye(DE)using bioinformatics methods, in order to reveal their potential molecular mechanisms.METHODS: Articles published in PubMed and EMBASE databases from the inception of the database to August 31, 2023, that used proteomic methods to detect protein expression in clinical samples of dry eye were searched. Differential proteins were selected and further analyzed using the STRING database and Cytoscape software for hub gene screening and module analysis. Protein-protein interaction(PPI)analysis, gene ontology(GO)functional annotation, and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed.RESULTS: A total of 21 articles were included, identifying 74 differentially expressed proteins. The most frequently occurring differential proteins were calgranulin A(SA1008), lipocalin-1(LCN1), lysozyme C(LYZ), mammaglobin-B(SCGB2A1), proline-rich protein 4(PRR4), transferrin(TF), and calgranulinB(S100A9). The top 10 hub genes were serum albumin(ALB), tumor necrosis factor(TNF), interleukin 6(IL6), IL1B, IL8, matrix metalloproteinase 9(MMP9), alpha-1-antitrypsin(SERPINA1), IL10, complement component 3(C3), and lactotransferrin(LTF). Module analysis suggested MMP9 and PRR4 as seed genes. KEGG analysis showed that differential proteins were mainly enriched in the IL17 signaling pathway(61.9%).CONCLUSION: The results reveal potential molecular targets and pathways for DE and confirm the association between the pathogenesis of DE and inflammation. Further in-depth research is needed to confirm the significance of these biomarkers in clinical practice.

Objective To assess the current state and influencing factors of multi-site work-related musculoskeletal disorders (WMSDs) among front-line employees in the assembly workshop of an automobile manufacturing enterprise. Methods A total of 394 front-line workers in the assembly workshop of an automobile manufacturing enterprise in Beijing City were selected as the research subjects using the judgmental sampling method. The Chinese version Musculoskeletal Disorders Questionnaire was used to assess the presence of WMSDs over the past 12 months in nine body regions: neck, shoulders, upper back, lower back, elbows, wrists, hips and thighs, knees, ankles and feet. The multivariable logistic regression was employed to investigate the influencing factors. Results The detection rate of overall WMSDs was 32.7% (129/394), with the top three single-site WMSDs being in the neck, shoulders, and lower back, and their detection rates were 14.0%, 12.7% and 9.6%, respectively. The detection rate of multi-site WMSDs was 17.8% (70/394). The result of multivariable logistic regression analysis revealed that workers who turned or bent their upper body while keeping their legs stationary, frequently performed wrist flexion/extension/lateral bending/rotation, or stood for prolonged period of time had significantly higher risks of developing multi-site WMSDs compared with those who did not (all P<0.05). Workers who perceived uncomfortable workplace lighting had higher risk of multi-site WMSDs than those who perceived it as comfortable (P<0.01). Conclusion The development of multi-site WMSDs among workers in the assembly workshop of this automobile manufacturing enterprise is strongly related to poor working postures at work.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Temporal interference (TI) is a form of stimulation that epitomizes an innovative and non-invasive approach for profound neuromodulation of the brain, a technique that has been validated in mice. Yet, the thin cranial bone structure of mice has a marginal influence on the effect of the TI technique and may not effectively showcase its effectiveness in larger animals. Based on this, we carried out TI stimulation experiments on rats. Following the TI intervention, analysis of electrophysiological data and immunofluorescence staining indicated the generation of a stimulation focus within the nucleus accumbens (depth, 8.5 mm) in rats. Our findings affirm the viability of the TI methodology in the presence of thick cranial bones, furnishing efficacious parameters for profound stimulation with TI administered under such conditions. This experiment not only sheds light on the intervention effects of TI deep in the brain but also furnishes robust evidence in support of its prospective clinical utility.
Animals ; Deep Brain Stimulation/methods* ; Nucleus Accumbens/physiology* ; Male ; Rats ; Rats, Sprague-Dawley ; Time Factors

A comprehensive phytochemical investigation of the leaves and twigs of Physalis angulata. var. villosa resulted in the isolation of 23 withanolide derivatives, including one novel 13,20-γ-lactone withanolide derivative (1) and three new withanolide derivatives (2-4). Architecturally, physalinin A (1) represents the first identified type B withanolide featuring a 13,20-γ-lactone moiety. The molecular structures of all isolates were elucidated using an integrated approach combining nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), infrared (IR) spectroscopy, and quantum chemical calculations to confirm structural assignments. The antiproliferative activities of all isolated withanolides were evaluated against four human cancer cell lines (HEL, HCT-116, Colo320DM, and MDA-MB-231). Among them, eight derivatives (2, 5-8, 14, 15, and 23) exhibited significant inhibitory effects, with half-maximal inhibitory concentration (IC₅₀) values of 0.18 ± 0.03 to 17.02 ± 0.21 μmol·L^-1. Structure-activity relationship (SAR) analysis suggested that the presence of an epoxide ring enhances anticancer activity, potentially through increased reactivity or specific interactions with molecular targets involved in cancer progression. These findings underscore the pharmacological potential of withanolides as promising lead compounds for the development of novel anticancer therapeutics.
Withanolides/isolation & purification* ; Physalis/chemistry* ; Humans ; Molecular Structure ; Cell Line, Tumor ; Antineoplastic Agents, Phytogenic/isolation & purification* ; Cell Proliferation/drug effects* ; Plant Leaves/chemistry* ; Plant Extracts/pharmacology*

Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD's inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
Extracellular Traps/immunology* ; Acute Lung Injury/immunology* ; Animals ; Sepsis/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neutrophils/immunology* ; Male ; Protein-Arginine Deiminase Type 4/genetics* ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Cytokines/metabolism*

Background During urbanization, the passenger load on urban public transport systems continues to increase, exposing bus drivers to a high risk of musculoskeletal disorders (MSDs). This occupational health issue may also potentially compromise public transport safety. Objective To investigate the prevalence of MSDs among bus drivers in a first-tier city and to explore associated influencing factors. Methods A self-administered questionnaire survey was conducted from December 2024 to March 2025 among 1300 bus drivers in a bus company. Data were collected on general demographic information, occupational activities, and MSDs indicators. A total of 1268 valid questionnaires were returned, yielding a response rate of 97.5%. Descriptive statistics were used to analyze the distribution characteristics of MSDs. Pearson χ² tests were employed to examine the association between MSDs prevalence and individual/occupational characteristics. Logistic regression was performed to identify the influencing factors of MSDs. Results The survey revealed that the prevalence of MSDs among the bus drivers was 28.5%, with the highest prevalence in the 41–50 years age group (30.5%). The conditions primarily affected the cervical spine (60.5%) and lumbar spine (61.9%), with some cases involving multiple sites. The logistic regression model indicated that the following factors were associated with a higher risk of MSDs: frequent smoking (OR=1.477), poor or moderate self-reported health status (OR=4.422), 11–20 years of service (OR=1.749), daily cumulative driving time ≥361 min (OR=1.616), frequent whole-body fatigue during driving (OR=2.077), occasional whole-body fatigue during driving (OR=1.873), feeling tense during driving (OR=1.518), fatigue after work (OR=2.485), work-related stress (OR=1.882), and prolonged smartphone use with head-down posture (OR=1.671). Conversely, occasional exercise (OR=0.713)/frequent exercise (OR=0.569), driving intervals ≥21 min per round (OR=0.645), and perceiving the driving seat comfortable (OR=0.429) were associated with a lower risk of MSDs. Conclusion Physical exercise, smoking, years of service, daily cumulative driving time, driving intervals per round, prolonged smartphone use with head-down posture, self-reported health status, and psychological factors such as work-related stress are influencing factors for MSDs among bus drivers. Drivers should increase physical exercise and change unhealthy living habits. Employers should optimize working conditions, arrange reasonable driving schedules, and foster a positive work environment to reduce MSDs prevalence.

Background During urbanization, the passenger load on urban public transport systems continues to increase, exposing bus drivers to a high risk of musculoskeletal disorders (MSDs). This occupational health issue may also potentially compromise public transport safety. Objective To investigate the prevalence of MSDs among bus drivers in a first-tier city and to explore associated influencing factors. Methods A self-administered questionnaire survey was conducted from December 2024 to March 2025 among 1300 bus drivers in a bus company. Data were collected on general demographic information, occupational activities, and MSDs indicators. A total of 1268 valid questionnaires were returned, yielding a response rate of 97.5%. Descriptive statistics were used to analyze the distribution characteristics of MSDs. Pearson χ² tests were employed to examine the association between MSDs prevalence and individual/occupational characteristics. Logistic regression was performed to identify the influencing factors of MSDs. Results The survey revealed that the prevalence of MSDs among the bus drivers was 28.5%, with the highest prevalence in the 41–50 years age group (30.5%). The conditions primarily affected the cervical spine (60.5%) and lumbar spine (61.9%), with some cases involving multiple sites. The logistic regression model indicated that the following factors were associated with a higher risk of MSDs: frequent smoking (OR=1.477), poor or moderate self-reported health status (OR=4.422), 11–20 years of service (OR=1.749), daily cumulative driving time ≥361 min (OR=1.616), frequent whole-body fatigue during driving (OR=2.077), occasional whole-body fatigue during driving (OR=1.873), feeling tense during driving (OR=1.518), fatigue after work (OR=2.485), work-related stress (OR=1.882), and prolonged smartphone use with head-down posture (OR=1.671). Conversely, occasional exercise (OR=0.713)/frequent exercise (OR=0.569), driving intervals ≥21 min per round (OR=0.645), and perceiving the driving seat comfortable (OR=0.429) were associated with a lower risk of MSDs. Conclusion Physical exercise, smoking, years of service, daily cumulative driving time, driving intervals per round, prolonged smartphone use with head-down posture, self-reported health status, and psychological factors such as work-related stress are influencing factors for MSDs among bus drivers. Drivers should increase physical exercise and change unhealthy living habits. Employers should optimize working conditions, arrange reasonable driving schedules, and foster a positive work environment to reduce MSDs prevalence.

Objective:To investigate the effect of laboratory indicators on hair loss in patients with female pattern hair loss (FPHL).Methods:Patients with FPHL who visited the Outpatient Clinic of the Department of Medical Aesthetics in Hangzhou First People’s Hospital from November 2022 to November 2023 were selected as the study group, and healthy women who matched the age of the study group in the physical examination center during the same period were selected as the control group. The general information of the patient was recorded, and was also tested by trichoscopy to rule out other patterns of alopecia. Representative indicators including testosterone, dehydroepiandrosterone sulfate(DHEA-S), thyroid-stimulating hormone, 25-hydroxyvitamin D, and serum ferritin were selected from laboratory tests for further analysis. Otherwise, the proportion of deficiency in vitamin D(<20 ng/ml) was calculated based on 25-hydroxyvitamin D levels (number of deficiency cases/total number of cases in each group×100%). Count data were presented as samples (percentages), and chi-square test was used for comparison between groups. Normally distributed continuous data were presented with Mean±SD, independent samples t-test was used for comparison between groups, M( Q1, Q3) was used for non-normally distributed continuous data, and Wilcoxon rank-sum test was used for comparison between groups. Multivariate logistic regression was used to analyze the influencing factors of FPHL. P<0.05 was statistically significant. Results:A total of 37 patients were selected in both groups. The mean age was (28.8±1.3) years in the study group and (29.6±0.9) years in the control group ( t=0.49, P=0.625). The body mass index was (22.8±0.4) kg/m 2 in the study group, and (23.5±0.3) kg/m 2 in the control group ( t=1.26, P=0.211). The testosterone level was 0.58 (0.49, 0.79) nmol/L in the study group, and 0.54 (0.50, 0.78) nmol/L in the control group( Z=1.42, P=0.157). The level of DHEA-S was 6.21 (5.18, 9.60) μmol/L in the study group, and 6.20 (5.20, 9.34) μmol/L in the control group ( Z=2.75, P=0.006). The level of thyroid-stimulating hormone was 2.56 (1.55, 3.66) mU/L in the study group and 1.49 (1.05, 2.65) mU/L in the control group ( Z=2.51, P=0.012). The level of 25-hydroxyvitamin D was 15.44 (11.80, 21.20) ng/ml in the study group, and the level of 25-hydroxyvitamin D was 20.32 (12.07, 21.20) ng/ml in the control group ( Z=2.30, P=0.021), and the proportion of 25-hydroxyvitamin D deficiency in the study group was 64.9% (24/37), which was higher than that in the control group [40.5% (15/37)] ( χ2=4.39, P=0.036). The serum ferritin level was 64.44 (39.47, 133.45) μg/L in the study group and 67.75 (52.63, 143.83) μg/L in the control group ( Z=0.70, P=0.484). The results of multivariate logistic regression analysis showed that the risk of FPHL was increased by the high level of DHEA-S and thyroid-stimulating hormone, and the low level of 25-hydroxyvitamin D (all P<0.05). Conclusion:Abnormal level of DHEA-S, thyroid-stimulating hormone, and 25-hydroxyvitamin D may be risk factors for FPHL.