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.

Rice is the world's largest food crop, and its yield and quality are directly related to food security and human health. Grain size, as one of the important factors determining the rice yield, has been widely concerned by breeders and researchers for a long time. To decipher the regulatory mechanism of rice grain size, we obtained a multi-tiller, dwarf, and small-grain mutant htd1 by ethyl methanesulfonate (EMS) mutation from the Japonica rice cultivar 'Zhonghua 11' ('ZH11'). Genetic analysis indicated that the phenotype of htd1 was controlled by a single recessive gene. Using the mutation site map (Mutmap) method, we identified the candidate gene OsHTD1, which encoded a carotenoid cleavage dioxygenase involved in the biosynthesis of strigolactone (SL). The SL content in htd1 was significantly lower than that in 'ZH11'. Cytological analysis showed that the grain size of the mutant decreased due to the reductions in the length and width of glume cells. The function of htd1 was further verified by the CRISPR/cas9 gene editing technology. The plants with the gene knockout exhibited similar grain size to the mutant. In addition, gene expression analysis showed that the expression levels of multiple grain size-related genes in the mutant changed significantly, suggesting that HTD1 may interact with other genes regulating grain size. This study provides a new theoretical basis for research on the regulatory mechanism of rice grain size and potential genetic resources for breeding the rice cultivars with high yields.
Oryza/growth & development* ; Mutation ; Edible Grain/growth & development* ; Alleles ; Plant Proteins/genetics* ; Dioxygenases/genetics* ; Lactones/metabolism* ; Gene Expression Regulation, Plant ; Genes, Plant ; Gene Editing ; CRISPR-Cas Systems ; Phenotype

Objective:To improve the understanding of recurrent adult Langerhans cell histiocytosis complicated with diabetes insipidus.Methods:The clinical data of 1 patient with recurrent adult Langerhans cell histiocytosis complicated with diabetes insipidus admitted to the First Affiliated Hospital of Shihezi University in January 2024 was collected. Its disease characteristics, effectiveness and safety of treatment scheme were analyzed, and literatures were reviewed.Results:The 42-year-old female patient was diagnosed as Langerhans cell histiocytosis in June 2021. After treated with cytarabine, the symptoms improved and the patient achieved sustained remission. In January 2024, the patient was admitted to the hospital due to pain in the middle part of the front chest. The PET-CT results indicated disease progression, which was manifested by new bone destruction, enlarged lymph nodes, and increased nocturnal urination, with urine volume of 3-5 L within 24 h. Based on the clinical manifestations such as cranial bone lesions, periorbital soft tissue lesions, and enlarged lymph nodes at onset, multiple systems and multiple foci involvement was considered. The diagnosis of combined diabetes insipidus was confirmed through the water deprivation and pressure test. After MACOP-B regimen (doxorubicin liposome, cyclophosphamide, vincristine, bleomycin, prednisone), the patient's bone pain was completely relieved, and no serious complications occurred.Conclusions:Recurrent adult Langerhans cell histiocytosis complicated with diabetes insipidus is rare; MACOP-B regimen is safe and effective in treatment of the disease.

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.

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 investigate the prognosis of patients with negative sentinel lymph nodes(SLN)after neoadjuvant chemotherapy(NAC)for breast cancer who are exempt from axillary lymph node dissection(ALND)and evaluate its safety in clinical treatment.Methods Clinical data of 2,163 patients initially diagnosed with breast cancer and having negative SLNs after NAC were se-lected from the SEER database from 2018 to 2021.Among them,373 patients underwent only SLN biopsy(SLNB group),and 1,790 patients underwent ALND(ALND group).Propensity score matching(PSM)was used to control for confounding factors,and the Kaplan-Meier method was em-ployed to analyze the overall survival rate.Univariate and multivariate Cox regression analyses were conducted to identify prognostic factors influencing the exemption from ALND in patients with negative SLNs after NAC for breast cancer.Results Before PSM,significant differences were observed be-tween the two groups in terms of clinical tumor stage,molecular subtype,estrogen receptor(ER)sta-tus,progesterone receptor(PR)status,human epidermal growth factor receptor 2(HER-2)status,efficacy of NAC,and breast surgery method(P＜0.05).After PSM,363 patients were included in each group.Univariate Cox regression analysis after PSM revealed that age,clinical tumor stage,and ER status were associated with overall survival(OS)of patients(P＜0.05).There was no sig-nificant difference in OS between patients who underwent SLNB and those who underwent ALND(P＞0.05).Multivariate Cox regression analysis indicated that age and clinical tumor stage were independent factors influencing OS in patients with negative SLNs after NAC.Survival curve analysis after PSM showed no statistically significant difference in overall survival rate between the SLNB and ALND groups(P=0.278).Conclusion Exemption from ALND in patients with negative SLNs af-ter NAC is feasible and does not affect the overall survival rate of patients.

OBJECTIVE: Salt-processed Psoraleae Fructus (SPF) is widely used as a phytoestrogen-like agent in the treatment of osteoporosis. However, due to improper clinical use or misuse, resulting in liver damage. In this study, network pharmacology was employed to analyze the mechanism of cholestatic liver damage. An adeno-associated virus overexpressing SULT1E1 (rAAV8-SULT1E1) was constructed and the hepatotoxicity of SPF, psoralen, and isopsoralen was determined. METHODS: By utilizing three databases inclding TCMSP, TCMID, and BATMAN- TCM, the targets of the three databases were summarized, and a total of 45 psoralen compounds were included. Network pharmacology analysis was then performed. The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity in vivo. SPF (10 g/kg), psoralen, and isopsoralen (50 mg/kg each) were intragastrically administered to mice for 30 d. B-ultrasound and samples were collected and examined for follow-up experiments. RESULTS: A total of 854 targets were predicted for 45 active components, with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF. A total of 126 pathways were enriched based on KEGG pathway analysis, with the "estrogen signaling pathway" identified as one of the top 20 pathways. In terms of pathological hepatic changes, treated mice had visually swollen hepatocytes, dilated bile ducts, and elevated serum biochemical markers, which were more prominent in mice treated with isopsoralen than in those treated with other compounds. Notably, the overexpression of SULT1E1 could reverse liver damage in each treatment group. B-ultrasound was used to observe the size of the gallbladder in vivo. The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-, psoralen-, and isopsoralen-treated groups, especially the SPF group. Compared with the expression levels in the negative control group (rAAV8-empty + con), the expression levels of FXR, Mrp2, Bsep, SULT1E1, SULT2A1, Ntcp, and Nrf2 decreased, whereas those of CYP7a1 and IL-6 increased in the SPF-, psoralen-, and isopsoralen-treated groups. CONCLUSION The overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators, indicating that SULT1E1 is an important target gene for SPF-induced liver damage. The severity of liver damage was significantly lower in the rAAV8-SULT1E1 groups than in the rAAV8-empty groups.

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.