Background Work-related musculoskeletal disorders (WMSDs) are a major occupational health concern, particularly among workers exposed to adverse ergonomic conditions. Manganese production involves heavy physical demands, yet research on WMSDs among manganese workers remains limited. Objective To investigate the prevalence and influencing factors of WMSDs among manganese workers in a manganese enterprise in Guangxi. Methods A cross-sectional survey was conducted from May to June 2024 on workers at a manganese factory in Guangxi. The Chinese Musculoskeletal Disorders Questionnaire was used to collect information on demographic characteristics, distribution of musculoskeletal symptoms, and work-related exposures. χ² test was applied to compare differences in positive WMSDs rates across groups, and logistic regression analysis was performed to identify associated factors. Results A total of 1476 workers were enrolled in the study after pre-determined inclusion and exclusion criteria. The overall prevalence of WMSDs was 34.15%. The most commonly affected body regions were the lower back (17.28%), neck (16.67%), and shoulders (13.82%). The results of logistic regression analysis indicated that female, older age, and education level of college or above were associated with a higher risk of WMSDs (P<0.05). Awkward working postures were significantly associated with WMSDs in corresponding body regions; in particular, awkward postures of the neck, upper limbs, trunk, and lower limbs were related to an increased risk of WMSDs in multiple body sites (P<0.05). In addition, poor lighting conditions, high workplace temperature, frequent or sustained arm support during work, and high job demands were associated with an increased risk of overall or site-specific WMSDs (P<0.05). Conclusion The high prevalence of WMSDs among manganese workers is closely associated with demographic characteristics, working postures, and work environment and organizational factors. Targeted ergonomic interventions focusing on high-risk body regions and key ergonomic exposures are warranted to reduce the risk of WMSDs among manganese workers.

ObjectiveThe nucleolar protein PES1 (Pescadillo homolog 1) plays critical roles in ribosome biogenesis and cell cycle regulation, yet its involvement in cellular senescence remains poorly understood. This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role. MethodsInitially, we assessed PES1 expression patterns in two distinct senescence models: replicative senescent mouse embryonic fibroblasts (MEFs) and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells. Subsequently, PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types. Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays, respectively. The expression of senescence-associated proteins (p53, p21, and Rb) and SASP factors (IL-6, IL-1β, and IL-8) were analyzed by Western blot or qPCR. Furthermore, Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology. ResultsPES1 expression was significantly downregulated in senescent MEFs and HepG2 cells. PES1 knockdown resulted in decreased EdU-positive cells and increased SA‑β‑gal-positive cells, indicating proliferation inhibition and senescence induction. Mechanistically, PES1 suppression activated the p53-p21 pathway without affecting Rb expression, while upregulating IL-6, IL-1β, and IL-8 production. Notably, PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress, as evidenced by aberrant nucleolar morphology. ConclusionOur findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent (but Rb-independent) cellular senescence, highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.

BACKGROUND: Spatiotemporal disparities exist in the disease burden of non-communicable diseases (NCDs) attributable to kidney dysfunction, which has been poorly assessed. The present study aimed to evaluate the spatiotemporal trends of the global burden of NCDs attributable to kidney dysfunction and to predict future trends. METHODS: Data on NCDs attributable to kidney dysfunction, quantified using deaths and disability-adjusted life-years (DALYs), were extracted from the Global Burden of Diseases Injuries, and Risk Factors (GBD) Study in 2019. Estimated annual percentage change (EAPC) of age-standardized rate (ASR) was calculated with linear regression to assess the changing trend. Pearson's correlation analysis was used to determine the association between ASR and sociodemographic index (SDI) for 21 GBD regions. A Bayesian age-period-cohort (BAPC) model was used to predict future trends up to 2040. RESULTS: Between 1990 and 2019, the absolute number of deaths and DALYs from NCDs attributable to kidney dysfunction increased globally. The death cases increased from 1,571,720 (95% uncertainty interval [UI]: 1,344,420-1,805,598) in 1990 to 3,161,552 (95% UI: 2,723,363-3,623,814) in 2019 for both sexes combined. Both the ASR of death and DALYs increased in Andean Latin America, the Caribbean, Central Latin America, Southeast Asia, Oceania, and Southern Sub-Saharan Africa. In contrast, the age-standardized metrics decreased in the high-income Asia Pacific region. The relationship between SDI and ASR of death and DALYs was negatively correlated. The BAPC model indicated that there would be approximately 5,806,780 death cases and 119,013,659 DALY cases in 2040 that could be attributed to kidney dysfunction. Age-standardized death of cardiovascular diseases (CVDs) and CKD attributable to kidney dysfunction were predicted to decrease and increase from 2020 to 2040, respectively. CONCLUSION NCDs attributable to kidney dysfunction remain a major public health concern worldwide. Efforts are required to attenuate the death and disability burden, particularly in low and low-to-middle SDI regions.
Humans ; Noncommunicable Diseases/epidemiology* ; Global Burden of Disease ; Disability-Adjusted Life Years ; Male ; Female ; Risk Factors ; Middle Aged ; Kidney Diseases/epidemiology* ; Bayes Theorem ; Adult ; Aged ; Global Health ; Quality-Adjusted Life Years

Objective:To investigate the metabolic pathways and potential molecular targets associated with dapagliflozin in the treatment of type 2 diabetes mellitus.Methods:Plasma samples from patients with type 2 diabetes mellitus were collected before and after 12 months of dapagliflozin treatment and analyzed using UPLC-VION IMS Q-Tof-based metabolomics and timsTOF Pro2 diaPASEF-based proteomics. Multivariate statistical analyses were performed to identify significant differences pre- and post-treatment. Correlation analysis was then conducted to assess relationships between differentially expressed metabolites and proteins closely associated with type 2 diabetes mellitus. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were used to construct metabolic pathway maps and predict therapeutic targets.Results:After 12 months of dapagliflozin treatment, 162 differential metabolites were identified, with 59 upregulated and 103 downregulated. A total of 440 differentially expressed proteins were detected, of which 272 were upregulated and 168 were downregulated. The main classes of differential metabolites included sphingolipids, glycerophospholipids, and glycosphingolipids. Key differentially expressed proteins included importin subunit alpha-11, synemin, Janus kinase 1, and far upstream element-binding protein 2. Correlation analysis revealed 98 shared enriched pathways between differential metabolites and proteins, involving neurotrophin signaling, chemokine signaling, and B cell receptor signaling pathways. Metabolic pathway analysis suggested that dapagliflozin might regulate insulin secretion by modulating glucose-dependent insulinotropic polypeptide, calmodulin-dependent protein kinase, and diacylglycerol levels.Conclusion:Dapagliflozin may exert therapeutic effects in type 2 diabetes mellitus through multiple mechanisms, including the modulation of metabolic and proteomic profiles, participation in key cellular signaling pathways, and regulation of insulin secretion.

Objective:To evaluate the efficacy of corticosteroids in male children with Duchenne muscular dystrophy (DMD), and provide evidence for the rational clinical use of medication.Methods:This was a multicenter medical record series study which conducted from January 15 th to March 14 th, 2025. A total of 53 male children with DMD admitted to the Department of Rehabilitation of Children′s Hospital, Zhejiang University School of Medicine, Children′s Hospital of Chongqing Medical University and Affiliated Children′s Hospital of Soochow University from 2020 to 2024 were enrolled. Clinical data, corticosteroid usage, and the follow-up data were collected. The North star ambulatory assessment (NSAA) was used as the primary efficacy indicator. Generalized estimating equations (GEE) exchangeable working matrices were used for longitudinal analysis, and the least squares mean were used to compare the change trend of the efficacy evaluation index across different medication durations. Results:The age at the initiation of corticosteroid treatment was (6.3±1.9) years. The follow-up duration was 1.2 (0.9, 2.2) years. After treatment, the raw scores and linear scores of NSAA were both significantly higher than those before treatment ((22±7) vs. (19±5) points, (60±16) vs. (53±8) points; t=3.98, 3.69; both P<0.001). The 10 meter running time and time rising from floor were both shorter than those before treatment (6 (4, 8) vs. 7 (6, 9) s, 5 (3, 6) vs. 6 (5, 9) s; Z=2.62, 3.47; both P<0.01). GEE model analysis revealed all nonlinear correlation between motor function (NSAA linear score, 10-meter running velocity, and rising from floor velocity) and the duration of corticosteroid treatment (all P<0.05). Least squares mean comparison all showed that the medication effect first increased and then decreased with duration, reaching the peak at 1.1-2.0 years after treatment (all P<0.05). Conclusions:Corticosteroids can improve the motor function in male children with DMD, with the maximum treatment effect occurring 1 to 2 years after the initiation of treatment. It is necessary to comprehensively leverage time-varying efficacy of corticosteroids to optimize individualized treatment regimens for maximal motor function benefits in children with DMD.

OBJECTIVE: To explore the predictive value of age, D-Dimer and fibrinogen (FIB) for non-thrombotic. METHODS: A retrospective analysis was conducted on a total of 1 384 coagulation test cases from January to August 2024 at Nanning No. 8 People's Hospital. Among them, the control group comprised 400 non-thrombotic cases with D-Dimer test results within the reference range. The thrombotic group comprised 57 clinically diagnosed thrombotic patients. The research group comprised 927 non-thrombotic cases with D-Dimer levels exceeding the reference range. The diagnosis treatment records, age information, plasma D-Dimer, and FIB test results of each group were collected. The changes and correlations of age, D-Dimer, and FIB indicators were compared and analyzed among the three groups. A new combination factor was generated by fitting a Logistic binary regression model. ROC curves were used to evaluate the predictive value of each index for non-thrombotic disease in both the research group and the thrombotic group. RESULTS: Compared with the control group, the thrombotic group and the research group had significantly higher age, D-Dimer, and FIB levels (P < 0.001). Further comparative analysis showed that the research group had significantly lower age and D-Dimer levels than the thrombotic group, the FIB level was significantly higher than that of the thrombotic group (P < 0.001). Spearman correlation analysis showed that the correlation coefficient between age and D-Dimer in the research group was higher than that in the control group and thrombotic group (P < 0.01), the thrombotic group had the highest negative correlation coefficient between FIB and D-Dimer (P < 0.01). The ROC curve analysis results showed that the AUC values of age, plasma D-dimer, and FIB independently predicted non-thromb diseases were 0.726, 0.735, and 0.611, respectively. A new combined factor was generated by fitting age, D-dimer, and FIB with a logistic binary regression model. The AUC value of the combined prediction of non-thrombotic diseases was the maximum at 0.832, which had high diagnostic value, and its sensitivity and specificity were 0.572 and 0.070. CONCLUSION Elevated D-dimer levels were associated with age, increased FIB, and a variety of non-thrombotic diseases, and combination of age, D-dimer, and FIB had a certain predictive value for non-thrombotic diseases, but the combined model had a low specificity, other information needs to be combined in the clinic to improve diagnostic accuracy.
Humans ; Fibrin Fibrinogen Degradation Products ; Retrospective Studies ; Fibrinogen ; Predictive Value of Tests ; Thrombosis ; Age Factors ; ROC Curve ; Male ; Female ; Middle Aged ; Adult

Objective To investigate the effect and safety of Sintilimab combined with Endostar injection in the treatment of programmed cell death ligand-1(PD-L1)positive lung squamous cell carcinoma(LSCC)in elderly patients.Methods A total of 94 elderly patients with PD-L1 positive LSCC diagnosed and treated from November 2019 to November 2021 were selected as the research subjects,and they were divided into the observation group(n=47)and the control group(n=47)by random number table method.The observation group was treated with Sintilimab combined with Endostar injection,and the control group was treated with Sintilimab.Twenty-one days constituted one treatment cycle,and they were treated for 3 consecutive cycles.The clinical efficacy and improvement rate of Karnofsky performance status(KPS)score in the two groups were statistically analyzed,as well as the tumor markers[carcinoembryonic antigen(CEA),cancer antigen 125(CA125),cytokeratin 19 fragment(CYFRA21-1)],angiogenesis factors[endostatin,insulin-like growth factor-1(IGF-1),vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF),and platelet-derived growth factor(PDGF)],apoptosis factor[B-cell lymphoma-2 gene(Bcl-2),Bcl-2-associated X protein(Bax),Livin protein,programmed cell death 5(PDCD5)]before and after treatment.The toxic and side effects during treatment,progression-free survival(PFS)and median survival time at 2-year follow-up were compared between the two groups.Results After treatment,the objective remission rate and disease control rate of the observation group were higher than those of the control group(P<0.01);after treatment,the improvement rate of KPS score in the observation group was higher than that in the control group(P<0.01).After treatment,the levels of serum CEA,CA125,and CYFRA21-1 in both groups decreased,and which were lower in the observation group than in the control group(P<0.05,P<0.01).After treatment,the levels of endostatin increased in both groups,while IGF-1,VEGF,bFGF,and PDGF decreased;the levels of endostatin in the observation group were higher than those in the control group,while the levels of IGF-1,VEGF,bFGF,and PDGF were lower than those in the control group(P<0.05,P<0.01).After treatment,the levels of Bcl-2 and Livin decreased in both groups,while Bax and PDCD5 increased;the levels of Bcl-2 and Livin in the observation group were lower than those in the control group,while the levels of Bax and PDCD5 were higher than those in the control group(P<0.05,P<0.01).There was no significant difference in toxic and side effects between the two groups during treatment(P>0.05).The 2-year survival rate and median survival time of the observation group were higher or longer than those of the control group(P<0.05).Conclusion The treatment of PD-L1 positive LSCC in elderly patients with Sintilimab combined with Endostar injection can improve the therapeutic effect and the survival status of patients,inhibit tumor angiogenesis,induce tumor apoptosis,prolong the survival time of patients,and has good safety.

Objective:To understand the current status of residents′ cognition of doctor-patient relationship and its influencing factors in a certain area of Guangxi under the background of Healthy China, so as to provide references for building the harmonious doctor-patient relationship.Methods:Convenience sampling was used to conduct an online questionnaire survey among permanent residents in a certain area of Guangxi from June 1 to July 31, 2023. The survey included residents′ sociodemographic characteristics and their perceptions of doctor-patient relationships. A logistic regression model was employed to analyze the influencing factors of residents′ perceptions of doctor-patient relationships.Results:A total of 114 796 residents participated in the survey. Among them, 44.1% (50 593) believed that the current doctor-patient relationship was harmonious, 47.8% (54 874) considered it neutral, and 8.1% (9 329) perceived it as discordant. The multinomial logistic regression model revealed that males, urban residents, older age groups, unmarried individuals, those with higher education levels, and those in poor health were more likely to perceive the doctor-patient relationship as discordant( P<0.05). Residents who valued health-related behaviors and knowledge, as well as those aware of health policies, were more likely to agree that the doctor-patient relationship was harmonious( P<0.05). Conclusions:Over 90% of residents in a certain area of Guangxi perceived the current doctor-patient relationship as either harmonious or neutral. Strengthening health education and enhancing the promotion of health policies can positively contribute to a harmonious doctor-patient relationship.

Objective:To investigate the clinical significance of prenatal screening and genetic analysis in the diagnosis of fetal aberrant right subclavian artery(ARSA).Methods:The ultrasonographic features of ARSA fetu-ses detected by prenatal ultrasound at the University of Hong Kong-Shenzhen Hospital from October 2017 to March 2022 were retrospectively analyzed.The fetuses were divided into isolated ARSA group and complicated ARSA group.Their genetic analysis results and pregnancy outcome were analyzed.Results:Among 30,260 preg-nant women,185 fetuses were diagnosed with ARSA by prenatal ultrasound screening,with an incidence of 0.6％;5 fetuses(2.6％)were diagnosed by ultrasound in the first trimester,and the remaining were diagnosed by fetal grade Ⅲ structural ultrasound examination at 20～24 weeks' gestation.Among them,158 fetuses(85.4％)had isolated ARSA,and 27(14.6％)had complicated ARSA.Among fetuses with ARSA and other structural abnormal-ities,cardiovascular system accounted for the highest proportion(44.4％),followed by nervous system(22.2％)and urinary system(22.2％).Through genetic analysis,8.3％(4/48)fetuses with isolated ARSA and 40.0％(4/10)fetuses with complicated ARSA were found to have chromosomal numerical or structural abnormalities,with statis-tically significant difference between the two groups(P=0.024).Genetic analysis was completed in 48 isolated ARSA,and the positive rate of pathogenic copy number variants(CNV)was 4.2％(2/48),which was not signifi-cantly different from the pathogenic CNV incidence rate of 0.4％(1/239)in elderly pregnant cases during the same period(P=0.074).The Down syndrome positive likelihood ratio(LR+)for isolated ARSA was 2.5 and the Down syndrome LR+for complicated ARSA was 49.6.Conclusions:Complicated ARSA is often associated with cardiovascular abnormalities and is more likely to develop Down syndrome than isolated ARSA.Although the inci-dence of pCNV in isolated ARSA is slightly higher than the natural incidence,the correlation between pCNV and i-solated ARSA has not been clearly determined by the current sample size.