Benchmark dose estimation based on Bayesian model averaging and its application to evaluation of cadmium exposure of population in Baiyin / 环境与职业医学

Background The optimal model method for estimation of benchmark dose (BMD) does not consider the uncertainty of model selection. There is a lack of studies on using Bayesian model averaging (BMA) to estimate BMD. Objective To apply BMA to the exposure assessment of cadmium pollution in China, discuss the role of BMA in estimating BMD based on dose-response models, and to provide methodological support for health risk assessment of hazardous substances. Methods The parameters of five dose-response models (Gamma, Log-logistic, Log-probit, Two-stage, and Weibull models) estimated from the data from a cadmium-contaminated area in Baiyin City of Gansu Province and the urinary cadmium ranges in five cadmium-contaminated areas in China were used to simulate the data of varied correct models with different numbers of dosage groups (5 and 8) and different sample sizes (50, 100, and 200), then the performance of BMA and traditional optimal model were compared. The case analysis used the cadmium exposure data in Baiyin, Gansu Province. All analyses set urinary cadmium as the indicator of cadmium exposure, the abnormal rate of β2-microglobulin as the effect indicator, and the benchmark response to 10%. The correct model (the model used when simulating data), optimal model [the model with smallest Akaike information criterion (AIC)], and BMA were used to estimate BMD and lower confidence limit of benchmark dose (BMDL); the BMDs, BMDLs, and relative deviations from different methods were compared. Results In the simulation study, with increasing sample size or the number of dosage groups, the intervals of the 5th percentile and the 90th percentile of BMD tended to be narrower; when the correct model was a single model, the relative deviation of BMD estimation by BMA was greater than that of the traditional optimal model; when the correct model was an equal weight mixed model, the relative deviation of BMD estimation by BMA was less than that by the traditional optimal model. For the data of cadmium-contaminated areas, the optimal model was a Log-probit model (AIC=1814.46), followed by a Log-logistic model (AIC=1814.57); the BMDs (BMDLs) estimated by the Log-probit model, the Log-logistic model, and BMA were 3.46 (2.68), 3.16 (2.33), and 2.92 (2.07) μg·g−1, respectively. Conclusion The traditional optimal model is still recommended when the correct model is known. However, when the dose-response relationship of a hazardous substance is uncertain or with different sources or exposure grouping, compared with the traditional optimal model, BMA theoretically provides more stable estimation of BMD and BMDL by considering multiple possible alternative models.

Nampt/Visfatin/PBEF: a functionally multi-faceted protein with a pivotal role in malignant tumors.

Nampt/Visfatin/PBEF is a primary, rate-limiting enzyme involved in NAD+ biosynthesis, which serves as a pivotal substance for proteins, and is required for cell growth, survival, DNA replication and repair and energy metabolism. Growing researches have elucidated that it is a pleiotropic protein that functions not only as an enzyme, but also as an adipocytokin, a growth factor, and a cytokine. Additionally, accumulated evidences indicate that Nampt is correlated to various malignant tumors, and complicated mechanisms are proposed to be involved in the carcinogenesis, progression, invasion and metastasis of it, including regulation of energy metabolism and genome instability, promotion of proliferation, angiogenesis, and tumor-promoting inflammation, resistance in cell death and avoidance of immune destruction. APO866 and CHS-828 are recognized inhibitors of Nampt, known to block the intracellular and extracellular NAD+ synthesis pathway. Both of them are currently in clinical trials for the treatment of various malignant tumors and have been shown to represent novel promising antitumor chemotherapeutic agents.

Progress of MRI in neonatal hypoxia ischemic encephalopathy / 国际儿科学杂志

Hypoxia ischemic encephalopathy(HIE) is the brain hypoxia ischemic damage resulted from perinatal hypoxia.MRI can reflect not only the anatomical and pathological changes of neonatal HIE,but also the molecular and metabolical changes in early stage,and evaluate the property and degree of HIE without radioactive damage,which is considered as an ideal imaging examination method for neonatal HIE.This review will summarize progresses in application of MRI to neonatal HIE diagnosis and prognosis.