Association of metals and bisphenols exposure with lipid profiles and dyslipidemia in Chinese adults: Independent, combined and interactive effects.

BACKGROUND: Although studies have assessed the association of metals and bisphenols with lipid metabolism, the observed results have been controversial, and limited knowledge exists about the combined and interactive effects of metals and bisphenols exposure on lipid metabolism. METHODS: Plasma metals and serum bisphenols concentrations were evaluated in 888 participants. Multiple linear regression and logistic regression models were conducted to assess individual associations of 18 metals and 3 bisphenols with 5 lipid profiles and dyslipidemia risk, respectively. The dose-response relationships of targeted contaminants with lipid profiles and dyslipidemia risk were captured by applying a restriction cubic spline (RCS) function. The bayesian kernel machine regression (BKMR) model was used to assess the overall effects of metals and bisphenols mixture on lipid profiles and dyslipidemia risk. The interactive effects of targeted contaminants on interested outcomes were explored by constructing an interaction model. RESULTS: Single-contaminant analyses revealed that exposure to iron (Fe), nickel (Ni), copper (Cu), arsenic (As), selenium (Se), strontium (Sr), and tin (Sn) was associated with elevated lipid levels. Cobalt (Co) showed a negative association with high density lipoprotein cholesterol (HDL-C). Bisphenol A (BPA) and bisphenol AF (BPAF) were associated with decreased HDL-C levels, with nonlinear associations observed. Vanadium (V), lead (Pb), and silver (Ag) displayed U-shaped dose-response relationships with most lipid profiles. Multi-contaminant analyses indicated positive trends between contaminants mixture and total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C). The interaction analyses showed that Se-Fe exhibited synergistic effects on LDL-C and non-HDL-C, and Se-Sn showed a synergistic effect on HDL-C. CONCLUSIONS: Our study suggested that exposure to metals and bisphenols was associated with changes in lipid levels, and demonstrated their combined and interactive effects.

Changes in muscle strength and risk of cardiovascular disease among middle-aged and older adults in China: Evidence from a prospective cohort study.

BACKGROUND: Evidence indicates that low muscle strength is associated with an increased cardiovascular diseases (CVDs) risk. However, the association between muscle strength changes based on repeated measurements and CVD incidence remains unclear. METHODS: The study used data from the China Health and Retirement Longitudinal Study in 2011 (Wave 1), 2013 (Wave 2), 2015 (Wave 3), and 2018 (Wave 4). Low muscle strength was defined as handgrip strength <28 kg for men or <18 kg for women, or chair-rising time ≥12 s. Based on changes in muscle strength from Waves 1 to 2, participants were categorized into four groups of Normal-Normal, Low-Normal, Normal-Low, and Low-Low. CVD events, including heart disease and stroke, were recorded using a self-reported questionnaire during Waves 3 and 4 visits. Cox proportional hazards models were used to investigate the association between muscle strength changes and CVD incidence after multivariable adjustments. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated with the Normal-Normal group as the reference. RESULTS: A total of 1164 CVD cases were identified among 6608 participants. Compared to participants with sustained normal muscle strength, the CVD risks increased progressively across groups of the Low-Normal (HR = 1.20, 95% CI: 1.01-1.43), the Normal-Low (HR = 1.35, 95% CI: 1.14-1.60), and the Low-Low (HR = 1.76, 95% CI: 1.49-2.07). Similar patterns were observed for the significant associations between muscle strength status and the incidence risks of heart disease and stroke. Subgroup analyses showed that the significant associations between CVD and muscle strength changes were consistent across age, sex, and body mass index (BMI) categories. CONCLUSIONS: The study found that muscle strength changes were associated with CVD risk. This suggests that continuous tracking of muscle status may be helpful in screening cardiovascular risk.

Sex-specific effect of perfluoroalkyl substances exposure on liver and thyroid function biomarkers: A mixture approach.

Although studies have investigated the effects of perfluoroalkyl substances (PFASs) on liver and thyroid function, little is known about its combined and sex-specific effect. A total of 688 participants were interviewed and serum PFASs concentration was measured using liquid chromatography/mass spectrometry. Five biomarkers of liver and thyroid function (ALT, GGT, TSH, FT3 and FT4) were chosen as outcomes. A restriction cubic spline function was applied to capture the dose-response relationship between PFASs and liver enzymes and thyroid hormones. Multivariable regression and Bayesian kernel machine regression (BKMR) models were performed to assess the single and overall associations of PFASs with targeted biomarkers. Single-pollutant analyses indicated that increased PFASs concentrations were associated with elevated ALT and GGT levels. BKMR models suggested positive dose-response relationships between PFASs mixtures and ALT and GGT levels. Significant associations were only detected between several PFASs and thyroid hormones, and joint effect of PFASs mixtures on FT3 levels was found at higher concentrations. Meanwhile, sex differences were found in the associations of PFASs with ALT and GGT levels, with significant results only in males. Our findings provide epidemiological evidence for combined and sex-specific effects of PFASs on ALT and GGT levels.

Association between exposure to perfluoroalkyl substances and uric acid in Chinese adults.

BACKGROUND: A growing body of evidence suggests the deleterious effects of perfluoroalkyl substances (PFASs) on kidney, but little is known on the association between PFASs joint exposure and uric acid. METHODS: Serum PFASs concentrations were measured in 661 participants recruited from Tianjin, China using liquid chromatography/mass spectrometry. The associations of single PFASs exposure with uric acid levels and hyperuricemia were assessed using multivariable linear and logistic regression models, respectively. Restricted cubic spline models were established to investigate the dose-response relationships between PFASs concentrations and uric acid levels. Bayesian Kernel Machine Regression (BKMR) model with a hierarchical variable selection was performed to assess the joint effect of PFASs on uric acid. RESULTS: Potassium perfluoro-1-octanesulfonate (PFOS) and perfluoro-n-octanoic acid (PFOA) were the dominated contributors with median concentrations of 16.80 ng/ml and 9.42 ng/ml, respectively. Increased PFOA concentration (per log2-unit) was associated with elevated uric acid level (ß = 0.088, 95% CI: 0.033-0.143) and higher risk of hyperuricemia (OR = 1.134, 95% CI: 1.006-1.289). Conversely, the estimated change of uric acid associated with log2-unit increment in perfluoro-n-decanoic acid (PFDA) was -0.081 mg/dL (95% CI: -0.154, -0.009). A significant linear dose-response pattern was found between log2-transformed PFOA concentration and uric acid level. BKMR analyses indicated a non-significant overall effect of PFASs mixture on uric acid. CONCLUSIONS: Significant associations between PFOA and PFDA and uric acid, and between PFOA and hyperuricemia were found in the single-pollutant models, but the joint effect of PFASs mixture on uric acid was not observed in the BKMR model, which provided new insights in regulation policies and risk assessment of PFASs.

A new prediction model for overall survival of elderly patients with solitary bone plasmacytoma: A population-based study.

Background: Comprehensive studies on the prognosis of solitary bone plasmacytoma (SPB) are lacking, especially in elderly patients with SPB. This study aims to establish a novel nomogram and risk stratification system to predict the overall survival (OS) of elderly patients with SPB. Methods: The data of elderly patients with SPB from 2000 to 2017 were identified in the SEER database. SPB patients were randomly assigned to the training set (n = 825) and validation set (n = 354). The Cox regression analysis was used to determine the independent risk factors for OS in elderly SPB patients. The nomogram was established and assessed by the area under the receiver operating curve (AUC), the consistency index (C-index), and the calibration plot. Patients were divided into low-, medium-, and high-risk groups based on the score of the nomogram. The Kaplan-Meier (K-M) curve was used to verify the differences in overall survival among the three groups. Result: A total of 1,179 elderly patients with SPB were included in the study. Age at diagnosis, prior cancer before SPB, marital status, radiotherapy, and chemotherapy were independent risk factors of OS. The AUC of the 3, 5, and 8-year OS in the training and validation sets were between 0.707 and 0.860. The C-index and calibration plot also indicated that the nomogram has great predictive accuracy and robustness. After risk stratification, patients in the high-risk group had the worst OS. Conclusion: A novel nomogram was built to predict the OS of elderly patients with SPB. It will help clinicians formulate more reasonable and personalized treatment strategies.

[Clinical Analysis of Bloodstream Infection after Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To analyze the clinical characteristics of bloodstream infection (BSI) in patients treated by hematopoietic stem cell transplantation (HSCT). METHODS: The clinical characteristics, distribution of pathogenic bacteria causing BSI and drug sensitivity of 910 patients treated by HSCT in our department from January 2013 to June 2020 were retrospectively analyzed. RESULTS: Among 910 HSCT patients, 111 patients were diagnosed as BSI within 100 days after transplantation, and 98 patients showed BSI during the period of agranulocytosis. Multivariate analysis showed that the usage of anti-thymocyte globulin (ATG), long duration of agranulocytosis and low infusion volume of mononuclear cell (MNC) were the independent risk factors affecting BSI after HSCT. Among 121 pathogenic bacteria isolated, 76 Gram-negative (G-) bacteria (62.8%), 40 Gram-positive (G+) bacteria (33.0%), and 5 fungi (4.1%) were detected out. The top three pathogens were Escherichia coli, Staphylococcus epidermidis and Pseudomonas aeruginosa. The drug-resistance rates of Escherichia coli and Klebsiella pneumoniae to carbapenems was 14.3% and 7.7%, respectively, and Pseudomonas aeruginosa was 66.7%. The susceptibility of G+ bacteria to vancomycin, linezolid and teicoplanin was 97.5%, 100% and 100%, respectively. The crude mortality rate of the patients with BSI at 100 days after HSCT was significantly higher than that of patients without BSI (P<0.001). CONCLUSION: The usage of ATG, long duration of agranulocytosis and low infusion volume of MNC are independent risk factors for BSI after HSCT. The pathogens after HSCT are mainly G- bacteria. Pseudomonas aeruginosa is highly resistant to carbapenems. Key words　　;

[Clinical and Bacteriological Analysis of Bacterial Bloodstream Infections in Patients with Acute Leukemial].

OBJECTIVE: To investigate the clinical characteristics, etiology and drug susceptibility of bacterial bloodstream infections in acute leukemia(AL) patients. METHODS: Clinical data, etiology and drug susceptibility of acute leukemia patients with bacterial bloodstream infections from April 2009 to April 2018 were retrospectively analyzed. RESULTS: A total of 376 strains were isolated, 76.9% was Gram-negative bacterial and 23.1% was Gram-positive bacteria. Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae were listed as the top three of Gram-negative bacteria. The susceptibility of Escherichia coli to the tigacycline, imipenem and meropenem was 100.0%, 98.2% and 98.1%, respectively. The susceptibility of Klebsiella pneumoniae to the tigacycline, imipenem and meropenem were 100.0%, 98.3% and 94.4%, respectively. The adjustment rate for initial use of carbopenems was 3.8%, while the adjustment rate for initial use of noncarbopenems was 74.3% in patients with main Gram-negative bacterial blood stream infection. The susceptibility of Gram-positive bacteria to glycopeptide antibiotics, linezolid and tigacycline was 100.0%. CONCLUSION: Gram-negative bacteria is the majority type of bacteria in AL patients with bacteria blood stream infections. The susceptibility of Gram-negative bacteria to the carbapenems is high, and the treatment adjustment rate is obviously low. The glycopeptide, linezolid and tigacycline are effective for Gram-positive bacteria infections..

Genome-scale integrated analysis to identify prospective molecular mechanisms and therapeutic targets in isocitrate dehydrogenase 2 R140Q-mutated acute myeloid leukemia.

The aim of the present study was to identify potential molecular mechanisms and therapeutic targets in regards to isocitrate dehydrogenase 2 (IDH2) R140Q-mutated acute myeloid leukemia (AML). An RNA sequencing dataset of IDH2 wild-type and R140Q-mutated adult de novo AML bone marrow samples was obtained from The Cancer Genome Atlas (TCGA) database. The edgeR package was used to screen for the differentially expressed genes (DEGs), and the potential molecular mechanisms and therapeutic targets were identified using Database for Annotation, Visualization, and Integrated Discovery (DAVID) v6.8, Biological Networks Gene Ontology tool, Connectivity Map (CMap), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and GeneMANIA. A total of 230 DEGs were identified between the bone marrow tissues of IDH2 R140Q-mutated and wild-type AML patients, of which 31 were significantly associated with overall survival (OS). Functional assessment of DEGs showed significant enrichment in multiple biological processes, including angiogenesis and cell differentiation. STRING and GeneMANIA were used to identify the hub genes of these DEGs. CMap analysis identified 13 potential small-molecule drugs against IDH2 R140Q-mutated adult de novo AML. Genome-wide co-expression network analysis identified several IDH2 R140Q co-expressed genes, of which 56 were significantly associated with AML OS. The difference in IDH2 mRNA expression levels and OS between the IDH2 R140Q-mutated and wild-type AML were not statistically significant in our cohort. In conclusion, we identified several co-expressing genes and potential molecular mechanisms that are instrumental in IDH2 R140Q-mutated adult de novo AML, along with 13 candidate targeted therapeutic drugs.