Background Lead smelting workers are exposed to mixed heavy metals such as lead (Pb) and cadmium (Cd). However, the specific associations and molecular mechanisms by which their combined exposure induces genetic damage remain unclear. Objective To clarify the association between combined Pb-Cd exposure and genetic damage and to explore the possible biological mechanisms through occupational epidemiological investigations and animal experiments. Methods (1) Population study: A cross-sectional study was conducted on 374 lead smelting workers in northern China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect urinary levels of 8 metals including Pb and Cd, and graphite furnace atomic absorption spectroscopy (GFAAS) was used to quantify blood levels of Pb and Cd. The cytokinesis-block micronucleus assay (CBMN) was used to assess genetic damage. Poisson regression was used to analyze the association between metal exposure and micronucleus rates. (2) In vivo experiment: Thirty SD rats were randomly assigned to five groups: control (pure water), Pb (300 mg·L⁻¹ lead acetate), Cd (50 mg·L⁻¹ cadmium chloride), combined exposure (Pb + Cd), and resveratrol intervention (Pb + Cd + 50 mg·L⁻¹ resveratrol). After 8 weeks of ad libitum drinking water exposure, liver pathology, oxidative stress indicators [reactive oxygen species (ROS), reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)], genetic damage (Comet assay and γ-H2AX) were evaluated. Furthermore, cell cycle distribution, apoptosis rates, and mRNA expression of DNA damage response (DDR), DNA repair, and apoptosis-related genes were measured. Results (1) The geometric mean (GM, 95%CI) of urinary Pb and Cd were 14.69 (13.14, 16.51) µg·L⁻¹ and 2.11 (1.90, 2.33) µg·L⁻¹, respectively; the blood Pb and Cd levels were 117.10 (105.59, 129.87) µg·L⁻¹ and 4.55 (4.23, 4.89) µg·L⁻¹, respectively among the 374 workers. The mean micronucleus rate was (1.64±0.081) ‰, with significantly higher rates in males (1.65±0.083) ‰ than females (1.53±0.334) ‰ (U=4.166, P=0.041). All Pb and Cd biomarkers were positively correlated with micronucleus rate (FR>1, P<0.05), with a significant interaction effect observed between Pb and Cd (FR>1, P<0.05). (2) In rats, co-exposure to Pb and Cd caused liver tissue damage and inflammatory infiltration. Significant increases were observed in lymphocyte ROS; GSSG and MDA in lung tissue increased, while GSH and CAT activity decreased. Comet assay indicators and γ-H2AX levels were significantly elevated. Co-exposure induced S-phase arrest and increased apoptosis. mRNA levels of DDR (ATM, ATR, Chk2, and P53) and pro-apoptotic genes (Bax and Caspase-3) were upregulated, while the anti-apoptotic gene Bcl-2 and DNA repair genes (BRCA1, BRCA2, RAD51, RAD52, and CtIP) were downregulated. Two-way ANOVA confirmed synergistic effects on GSSG, Comet assay indicators, and ATR/Chk2 mRNA expression. Conclusion Occupational co-exposure to Pb and Cd synergistically induces genetic damage. This damage is mediated by oxidative stress and DNA damage, which activates the DDR pathway and inhibits the expression of DNA repair genes, ultimately leading to cell cycle arrest and apoptosis.

Background Lead smelting workers are exposed to mixed heavy metals such as lead (Pb) and cadmium (Cd). However, the specific associations and molecular mechanisms by which their combined exposure induces genetic damage remain unclear. Objective To clarify the association between combined Pb-Cd exposure and genetic damage and to explore the possible biological mechanisms through occupational epidemiological investigations and animal experiments. Methods (1) Population study: A cross-sectional study was conducted on 374 lead smelting workers in northern China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect urinary levels of 8 metals including Pb and Cd, and graphite furnace atomic absorption spectroscopy (GFAAS) was used to quantify blood levels of Pb and Cd. The cytokinesis-block micronucleus assay (CBMN) was used to assess genetic damage. Poisson regression was used to analyze the association between metal exposure and micronucleus rates. (2) In vivo experiment: Thirty SD rats were randomly assigned to five groups: control (pure water), Pb (300 mg·L⁻¹ lead acetate), Cd (50 mg·L⁻¹ cadmium chloride), combined exposure (Pb + Cd), and resveratrol intervention (Pb + Cd + 50 mg·L⁻¹ resveratrol). After 8 weeks of ad libitum drinking water exposure, liver pathology, oxidative stress indicators [reactive oxygen species (ROS), reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)], genetic damage (Comet assay and γ-H2AX) were evaluated. Furthermore, cell cycle distribution, apoptosis rates, and mRNA expression of DNA damage response (DDR), DNA repair, and apoptosis-related genes were measured. Results (1) The geometric mean (GM, 95%CI) of urinary Pb and Cd were 14.69 (13.14, 16.51) µg·L⁻¹ and 2.11 (1.90, 2.33) µg·L⁻¹, respectively; the blood Pb and Cd levels were 117.10 (105.59, 129.87) µg·L⁻¹ and 4.55 (4.23, 4.89) µg·L⁻¹, respectively among the 374 workers. The mean micronucleus rate was (1.64±0.081) ‰, with significantly higher rates in males (1.65±0.083) ‰ than females (1.53±0.334) ‰ (U=4.166, P=0.041). All Pb and Cd biomarkers were positively correlated with micronucleus rate (FR>1, P<0.05), with a significant interaction effect observed between Pb and Cd (FR>1, P<0.05). (2) In rats, co-exposure to Pb and Cd caused liver tissue damage and inflammatory infiltration. Significant increases were observed in lymphocyte ROS; GSSG and MDA in lung tissue increased, while GSH and CAT activity decreased. Comet assay indicators and γ-H2AX levels were significantly elevated. Co-exposure induced S-phase arrest and increased apoptosis. mRNA levels of DDR (ATM, ATR, Chk2, and P53) and pro-apoptotic genes (Bax and Caspase-3) were upregulated, while the anti-apoptotic gene Bcl-2 and DNA repair genes (BRCA1, BRCA2, RAD51, RAD52, and CtIP) were downregulated. Two-way ANOVA confirmed synergistic effects on GSSG, Comet assay indicators, and ATR/Chk2 mRNA expression. Conclusion Occupational co-exposure to Pb and Cd synergistically induces genetic damage. This damage is mediated by oxidative stress and DNA damage, which activates the DDR pathway and inhibits the expression of DNA repair genes, ultimately leading to cell cycle arrest and apoptosis.

Objective To construct and validate a prediction model for urosepsis in patients after upper urinary tract stone surgery using various machine learning algorithms.Methods A total of 7 464 upper urinary tract stone patients who underwent surgery at the Sixth Affiliated Hospital of Guangxi Medical University from Jun.2018 to Jun.2023 were enrolled and randomly assigned to training(5 224 cases)or validation sets(2 240 cases)at a ratio of 7∶3.Among them,622(8.33%)cases developed urosepsis postoperatively.Six machine learning algorithms,including extreme gradient boosting(XGBoost),logistic regression,light gradient boosting machine(LightGBM),random forest(RF),adaptive boosting(AdaBoost),and gradient boosting decision tree(GBDT),were used to construct prediction models for postoperative urosepsis.The model's predictive ability and clinical benefits were evaluated using receiver operating characteristic(ROC)curves,Shapley additive explanation(SHAP)analysis,calibration curves,and decision curve analysis(DCA).Results The clinical features included body mass index(BMI),number of surgeries,heart rate,Barthel index,venous thrombo embolism(VTE)risk assessment,gender,American Society of Anesthesiologists(ASA)grade,urinary nitrite,and urinary leukocyte in the models.In the training set,the XGBoost,LightGBM,and RF models performed excellently,with area under curve(AUC)values of ROC curves reaching 1.00.In the validation set,the logistic regression model performed the best,with an AUC value of ROC curve of 0.76,showing good predictive stability and calibration.The AdaBoost and GBDT models followed with AUC values of 0.74 and 0.75,respectively,while the AUC values of the LightGBM,XGBoost,and RF models were 0.71,0.70,and 0.68.In terms of model interpretability,SHAP analysis showed the contribution of variables in a descending order as:heart rate,urinary leukocytes,gender,BMI,Barthel index,VTE risk assessment,urinary nitrite,number of surgeries,and ASA grade.Conclusion A logistic regression model for early risk prediction of postoperative urosepsis in upper urinary tract stone patients has been successfully constructed.This model has good predictive performance and calibration,and can effectively assist clinical diagnosis.

To explore the inhibitory effect of ginkgolide B (GB) on MH7A human fibroblast-like synoviocytes (FLS) and its potential mechanism. Firstly, 20 μg/L tumor necrosis factor-α (TNF-α) was pretreated with MH7A to establish a cell model of arthritis. After incubation of MH7A cells with various concentrations of GB, CCK-8 assay, Transwell assay, and flow cytometry (FCM) were separately used to detect cell viability, cell invasion, and cell apoptosis rate and cell cycle; Real-time quantitative PCR and Western blot assay were performed to detect the apoptosis- and cycle-related gene transcriptions and protein expressions, respectively. The results showed that compared with the control group, GB dose- and time-dependently suppressed cell viability to a greater extent; GB significantly reduced cell invasive ability and increased cell apoptosis rate and proportion of G0/G1 phase in MH7A cells, along with increased transcription levels of Bcl-2-associated X protein (Bax) and p21 mRNA and decreased transcription levels of Bcl-2, myeloid cell leukemia 1(Mcl-1), protein kinase B (PKB; AKT), IP3K, Cyclin D1 and cyclin-dependent kinase 4 (CDK4) mRNA; GB remarkably increased expression levels of Bax, p21, and cleaved-Caspase 3 protein and decreased expression levels of Bcl-2, Mcl-1, p-AKT, p-PI3K, Cyclin D1, and CDK4 protein, with decreased ratios of p-PI3K/PI3K, p-AKT/AKT, and Bcl-2/Bax. In conclusion, GB blocks the G1-to-S cell cycle transition, suppresses cell viability and cell invasion and induces cell apoptosis of MH7A human RA-FLS via suppressing the PI3K/AKT signaling pathway.

Objective To understand the serologic prevalence and infection status of Cytomegalovirus(CMV)in children aged 0～1 years,and explore the risk factors of CMV infection for clinical reference.Methods The data of 4 938 children aged 0～1 years who underwent chemiluminescence enzyme immunoassay for TORCH in Department of Inpatient and Department of Pediatrics Outpatient of Maternal and Child Health Hospital of Inner Mongolia from January 2020 to December 2022 were retrospectively analyzed to understand the seroprevalence of human CMV(HCMV)among children in the region,and analyzed the risk factors associated with HCMV infections by combining the results of laboratory tests and clinical information.Results In 4 938 children,the total antibody positivity rate was 94.01%(4 642/4 938),the total IgG antibody positivity rate was 93.86%(4 635/4 938),the total IgM antibody positivity rate was 8.10%(400/4 938),and the positive rate of the two simultaneous detections was 7.96%(393/4 938).The difference in HCMV-IgG and HCMV-IgM antibodies positivity rates beteen different age groups were statistically significant(χ2=36.350,1 043.199,all P<0.05),and the differences in HCMV-IgG and IgM antibodies between boys and girls were not statistically significant(χ2=0.215,1.184,all P＞0.05).According to univariate analysis,the breast-feeding and vaginal delivery rates in the infected group were higher than those in the control group,and the differences in feeding and birth methods were statistically significant(χ2=10.777,5.725,all P<0.05).Multifactorial analysis found that breast-feeding and transvaginal delivery were independent risk factors for HCMV infection,and the differences was statistically significant(Wald χ2=6.247,10.057,all P<0.05).Conclusion The serologic antibody positivity rate of HCMV in children within 1 year of age is as high as 94.01%,and infants aged 3 months to 6 months are most susceptible to infection.Breastfeeding and transvaginal delivery are independent risk factors for HCMV infection in children within 1 year of age.

Objective To understand the serologic prevalence and infection status of Cytomegalovirus(CMV)in children aged 0～1 years,and explore the risk factors of CMV infection for clinical reference.Methods The data of 4 938 children aged 0～1 years who underwent chemiluminescence enzyme immunoassay for TORCH in Department of Inpatient and Department of Pediatrics Outpatient of Maternal and Child Health Hospital of Inner Mongolia from January 2020 to December 2022 were retrospectively analyzed to understand the seroprevalence of human CMV(HCMV)among children in the region,and analyzed the risk factors associated with HCMV infections by combining the results of laboratory tests and clinical information.Results In 4 938 children,the total antibody positivity rate was 94.01%(4 642/4 938),the total IgG antibody positivity rate was 93.86%(4 635/4 938),the total IgM antibody positivity rate was 8.10%(400/4 938),and the positive rate of the two simultaneous detections was 7.96%(393/4 938).The difference in HCMV-IgG and HCMV-IgM antibodies positivity rates beteen different age groups were statistically significant(χ2=36.350,1 043.199,all P<0.05),and the differences in HCMV-IgG and IgM antibodies between boys and girls were not statistically significant(χ2=0.215,1.184,all P＞0.05).According to univariate analysis,the breast-feeding and vaginal delivery rates in the infected group were higher than those in the control group,and the differences in feeding and birth methods were statistically significant(χ2=10.777,5.725,all P<0.05).Multifactorial analysis found that breast-feeding and transvaginal delivery were independent risk factors for HCMV infection,and the differences was statistically significant(Wald χ2=6.247,10.057,all P<0.05).Conclusion The serologic antibody positivity rate of HCMV in children within 1 year of age is as high as 94.01%,and infants aged 3 months to 6 months are most susceptible to infection.Breastfeeding and transvaginal delivery are independent risk factors for HCMV infection in children within 1 year of age.

Objective:To study the correlation between serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and echocardiographic parameters in patients with chronic Keshan disease, providing reference for diagnosis and prognosis evaluation of chronic Keshan disease.Methods:Ninety-nine patients with chronic Keshan disease who received standardized treatment at Jingchuan County People's Hospital in Pingliang City, Gansu Province from January to December 2020 were selected. Among them, 16 patients were classified as cardiac function grade Ⅱ according to New York Heart Association (NYHA), 69 as grade Ⅲ and 14 as grade Ⅳ. The patients underwent echocardiography and their serum NT-proBNP level was measured using fluorescence immunochromatography. The differences in serum NT-proBNP levels among patients with different cardiac function grades were compared, and the correlation between cardiac function grades, serum NT-proBNP level and echocardiographic parameters was analyzed.Results:The serum NT-proBNP levels in patients with cardiac function grades Ⅱ, Ⅲ, and Ⅳ were (1 107.26 ± 268.03), (2 125.98 ± 293.02), and (8 268.59 ± 2 659.50) pg/ml, respectively. The differences among the three groups were statistically significant ( F = 13.94, P < 0.001). The serum NT-proBNP level was positively correlated with cardiac function grades ( r = 0.44, P < 0.001), left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and left atrial diameter ( r = 0.45, 0.52, 0.38, P < 0.001), and negatively correlated with fractional shortening and left ventricular ejection fraction ( r = - 0.39, - 0.46, P < 0.001). Conclusions:The serum NT-proBNP level in patients with chronic Keshan disease with different cardiac function grades is different, and is positively correlated with echocardiographic parameters reflecting the degree of cardiac structural and functional impairment. The NT-proBNP level may become an early diagnostic, grading, and prognostic indicator for chronic Keshan disease.

30 patients with chronic periodontitis and Type 2 diabetes mellituse were included.By a split-mouth design,the teeth in the left side were served as the experiment group and given Nd∶YAG and Er∶YAG laser therapy adjunctive to conventional periodontal treatment;the teeth in the right side were served as the control group and given conventional periodontal treatment alone.Before and after treatment perio-dontal and CBCT image indexes were examinde and compare between the 2 groups.Before treatment all the indexes were not statistically dif-ferent between the 2 groups(P＞0.05).3 months after treatment,the bleeding index(BI)and probing depth(PD)of the experimental group were significantly lower than those of the control group(P＜0.05).6 months after treatment,BI,PD and attachment loss(AL)in the experi-mental group were significantly lower than those in the control group,and the surface area and volume of the root in the alveolar bone were significantly higher than those in the control group(P＜0.05).Nd∶YAG and Er∶YAG laser therapy adjunctive to conventional periodontal treatment is more effective than conventional periodontal treatment alone in the treatment of chronic periodontitis with type 2 diabetes melli-tus.

Objective:To analyze the association between waist circumference (WC) and ischemic stroke (IS).Methods:The data for the present study were from the prospective cohort study of China Kadoorie Biobank in Qingdao. Using baseline information and IS events of the participants, the Cox proportional hazard regression model and restricted cubic spline (RCS) were used to analyze the association between WC and IS.Results:A total of 33 355 participants were included in the study, with 302 008.88 person-years of follow-up. A total of 1 093 new cases of IS were observed. Multivariate Cox proportional hazard regression model analysis showed that compared to the respondents with normal WC (male <85.0 cm, female <80.0 cm), respondents with excessive WC (male ≥85.0 cm, female ≥80.0 cm) had a 78% higher risk of IS incidence [hazard ratio( HR)=1.78, 95% CI: 1.51-2.10], and the risk increased by 72% ( HR=1.72, 95% CI: 1.40-2.12) and 83% ( HR=1.83, 95% CI: 1.40-2.39) in men and women. According to the RCS, the increase in WC and the risk of IS showed an "S" trend of nonlinear dose-response relationship. Conclusions:The risk of IS would increase with the WC. Keeping a normal WC is important for preventing IS.

Objective To investigate the effect of Huangzhi oral liquid on ferroptosis and apoptosis of hepatocytes in acute hyperlipidemia mice based on abnormal lipid metabolism.Methods Forty SPF grade C57BL/6 mice were randomly assigned to the normal control group,the model group,Huangzhi oral liquid low-dose and high-dose groups,and fenofibrate group,with 8 mice in each group.All administration groups were given Huangzhi oral liquid and fenofibrate by gavage at corresponding doses,while the normal control group and the model group were given the same dose of distilled water for a period of 5 days.on the third day of administration,in addition to the normal control group,other groups were injected intramuscularly with Triton WR-1339 to establish a hyperlipidemia model.After the administration,the serum lipid levels and liver function in mice were detected.The pathological changes of liver were observed by HE staining and lipid accumulation was observed by oil red O staining.The iron content in liver tissues was detected by tissue iron assay kit.The changes in protein expression of ABCA1,ABCG5,LXRα,ASGR1,cleaved-PARP,cleaved-caspase 3,Bcl2,Bax,TFR1,SLC7A11,GCLM,GPX4 and FTH1 in liver were detected by Western Blot.Results Compared with the model group,Huangzhi oral liquid could reduce the lipid vacuoles in liver tissues,alleviate the degree of lipid degeneration,reduce the content of TC,TG,LDL-C,AST and ALT in serum,increase the content of HDL-C,increase the protein expression levels of ABCA1,ABCG5,LXRα,Bcl-2,SLC7A11,GCLM,GPX4 and FTH1 in mice liver tissues,reduce the protein expression levels of ASGR1,cleaved-PARP,cleaved-caspase 3,Bax and TFR1.Conclusion Huangzhi oral liquid can alleviate the abnormal lipid metabolism in acute hyperlipidemia mice,thus alleviates hepatocyte apoptosis and ferroptosis.