First Insight into the Formation of In Vivo Transformation Products of 2-Ethylhexyl diphenyl phosphate in Zebrafish and Prediction of Their Potential Toxicities.

As a frequently detected organophosphorus flame retardant in the environment, 2-ethylhexyl diphenyl phosphate (EHDPHP) is vulnerable to biotransformation, while the transformation mechanisms and potential toxicities of its transformation products remain unclear. In the present study, in vivo transformation products of EHDPHP in exposed zebrafish for 21d were analyzed by suspect screening and identified by mass spectrometry. Fifteen metabolites were identified, including 10 phase I and 5 phase II products with monohydroxylated products being primary, among which 5-OH-EHDPHP was the most predominant. Two sulfation products and one terminal desaturation metabolite of EHDPHP were reported for the first time. A density functional calculation coupled with molecular docking disclosed that the specific conformation of EHDPHP docked in the protein pockets favored the primary formation of 5-OH-EHDPHP, which was fortified to be a more suitable biomarker of EHDPHP exposure. The in vitro tests suggested that EHDPHP transformation took place not only in liver but also in intestine, where gut microbes played an important role. Due to lack of standards, in silico toxicity prediction combined with molecular docking indicated that several metabolites potentially cause higher toxicities than EHDPHP. The results provide deep insight into the potential health risks due to specific in vivo transformation of EHDPHP.

Association Between Hemoglobin and Major Adverse Cardiac Events: A Secondary Analysis from A Retrospective Cohort Study.

BACKGROUND: This study aims to investigate the association between hemoglobin and major adverse cardiac events (MACE) in patients with stable coronary artery disease (CAD) who were treated with percutaneous coronary intervention (PCI). METHODS: This was a secondary analysis based on a retrospective cohort study involving 204 patients with stable CAD. Patients were divided into four groups according to hemoglobin levels (Q1: 6.90-12.30 g/dL; Q2: 12.40-13.80 g/dL; Q3: 13.90-14.90 g/dL; Q4: 15.00-19.00 g/dL). Lasso regression analysis was performed to select characteristic variables and reduce dimensions. Odds ratio (OR) and 95% confidence interval (CI) were used for comparing data among groups. RESULTS: After an average follow-up of 783 days, 28/204 (17.72%) patients with CAD developed MACE. Univariate analysis data showed that hemoglobin level was negatively associated with the incidence of MACE in patients with CAD treated with PCI (Q2 vs Q1: OR=0.19, P=0.005; Q3 vs Q1: OR=0.25, P=0.013; Q4 vs Q1: OR=0.13, P=0.002). The negative correlation between hemoglobin and MACE still existed after adjusting selected variables obtained from multivariate regression analysis (Q2 vs Q1: OR= 0.18, P=0.007; Q3 vs Q1: OR=0.29, P=0.038; Q4 vs Q1: OR=0.19, P=0.016). Curve fitting illustrated that hemoglobin level presented a non-linear and negative association with MACE in patients with CAD treated with PCI. CONCLUSIONS: Hemoglobin level can be utilized as a prognostic indicator of MACE in patients with CAD after PCI.

Association of body mass index with bladder cancer risk: a dose-response meta-analysis of prospective cohort studies.

Prospective epidemiologic studies on the association between body mass index (BMI) and bladder cancer yielded inconsistent findings. This study sought to quantitatively summarize the evidence by performing a dose-response meta-analysis on prospective cohort studies. Eligible studies were retrieved via PubMed and Embase databases, and by manual review of the references. Linear and nonlinear trend analyses were conducted to explore the relationships between BMI and bladder cancer risk. Meta-analyses on the categories of overweight and obesity were also conducted. The summary relative risk (SRR) was estimated. Heterogeneity across the studies was explored through subgroup analyses based on gender, age, year of publication, sample size, assessment of BMI, geographic location, physical activity and family history of cancer. A total of 14 prospective cohort studies involving 12,642 cases were included. Result of the dose-response analysis showed a nonlinear positive relationship between BMI and bladder cancer (SRR = 1.03, 95% CI: 1.01-1.06, P-nonlinearity =0.031), suggesting that per 5 kg/m2 increment on BMI corresponded to a 3.1 % increase of bladder cancer risk, especially BMI exceed 30kg/m2.Furthermore, significant positive association was also observed between obesity category and bladder cancer risk (SRR: 1.10, 95%CI: 1.03-1.17). In summary, this dose-response meta-analysis suggests a nonlinear positive association between BMI and bladder cancer risk. Further studies are required to confirm these findings and elucidate the pathogenic mechanisms.