中国成年人生活方式和心血管代谢因素与甲基化年龄加速的相关性分析

目的比较分析5种甲基化年龄加速指标与生活方式和心血管代谢因素间的相关性。方法基于中国慢性病前瞻性研究中有基线外周血全基因组甲基化检测数据的研究对象980人, 计算Horvath时钟、Hannum时钟、DNAm PhenoAge、GrimAge和Li时钟5种甲基化年龄。根据甲基化年龄对实足年龄回归的残差值计算甲基化年龄加速。研究的生活方式因素包括吸烟、饮酒、饮食习惯、体力活动、经BMI和腰围联合定义的体型。心血管代谢因素包括血压、血糖和TC。利用一般线性模型分析生活方式和心血管代谢因素与各甲基化年龄加速指标的相关性[β值(95%CI)]。结果 GrimAge加速指标与吸烟、饮酒、体力活动水平及BMI存在关联。与不吸烟、不饮酒或BMI为18.5～23.9 kg/m2 者相比, 吸烟者(每天吸烟1～14、15～24、≥25支者对应的β值依次为0.71(95%CI:0.57～0.86)、0.88(95%CI:0.73～1.03)、0.99(95%CI:0.81～1.18)、重度饮酒者[每日纯乙醇量≥60 g:0.33(95%CI:0.11～0.55)]、BMI<18.5 kg/m2者[0...     

中国10个地区成年人共病流行特征分析

目的 描述中国成年人的共病流行情况及其长期变化,以及常见的共病模式。方法 本研究纳入参与中国慢性病前瞻性研究第二次重复调查的25 033人,利用研究对象参加2004-2008年基线调查和2013-2014年第二次重复调查时采集的信息进行分析。根据自报疾病史、现场体格检查及血液样本检测等信息定义了13种慢性病或健康问题,将共病定义为同时患有≥2种慢性病或健康问题。采用系统聚类分析法描述共病模式。结果 研究对象在基线调查时的年龄为（51.5±10.1）岁,第二次重复调查时为（59.5±10.2）岁。2次调查平均间隔时间（8.0±0.8）年,共病率由33.5%上升至58.1%,人均患病数由1.15个增加至1.82个,平均每5年增长0.42个患病数。年长者、城市人群、文化程度低者的共病率较高,且患病数量随年龄的增速更快。吸烟及过量饮酒者的患病数量随年龄增速也更快。该人群中最常见的共病组合为：超重肥胖、高血压、糖尿病、中风和冠心病。结论 我国成年人群共病率较高,且随年龄增长而增加。共病情况在不同地区、文化程度水平和不同生活方式人群中存在差异。     

S1PR1 expression correlates with inflammatory responses to Newcastle disease virus infection

Newcastle disease virus (NDV) is the causative agent of Newcastle disease, which is characterized by inflammatory pathological changes in the organs of chickens. The inflammatory response to this disease has not been well characterized. Previous reports showed that the sphingosine-1-phosphate-1 receptor (S1PR1), a G protein-coupled receptor, is important to the activation of inflammatory responses. To understand better the viral pathogenesis and host inflammatory response, we analyzed S1PR1 expression during NDV infection. We observed a direct correlation between chicken embryo fibroblast (CEF) cellular inflammatory responses and S1PR1 expression. Virulent NDV-infected CEF cells also had elevated levels of pro-inflammatory cytokines (IL-1β, IL-6 and IL-18). When S1PR1 was inhibited by using the specific antagonist W146, pro-inflammatory cytokine production declined. Overexpression of S1PR1 resulted in increased virus-induced IL-1β production. S1PR1 expression levels did not impact significantly NDV replication. These findings highlight the important role of S1PR1 in inflammatory responses in NDV infection.     

Association of heart rate and diabetes among 0.5 million adults in the China Kadoorie biobank: Results from observational and Mendelian randomization analyses

Background and aimsObservational studies have associated resting heart rate with incident diabetes. Whether the associations are causal remains unclear. We aimed to examine the shape and strength of the associations and assessed the causal relevance of such associations in Chinese adults.Methods and resultsThe China Kadoorie Biobank enrolled 512,891 adults in China. Cox proportional hazard regression models was conducted to estimate hazard ratios (HRs) for the associations of resting heart rate with type 2 diabetes and total diabetes. Among 92,724 participants, 36 single-nucleotide polymorphisms (SNPs) related to resting heart rate were used to construct genetic risk score. We used Mendelian randomization analyses to make the causal inferences. During a median follow-up of 9 years, 7872 incident type 2 diabetes and 13,349 incident total diabetes were documented. After regression dilution bias adjustment, each 10 bpm higher heart rate was associated with about a 26% higher risk of type 2 diabetes (HR, 1.26 [95% CI, 1.23, 1.29]) and 23% higher risk of total diabetes (HR, 1.23 [95% CI, 1.20, 1.26]). Instrumental variable analyses showed participants at top quintile compared with those at bottom quintile had 30% higher risk for type 2 diabetes (HR, 1.30 [95% CI, 1.17, 1.43]), and 10% higher risk for total diabetes (HR, 1.10 [95% CI, 1.02, 1.20]).ConclusionsThis study provides evidence that resting heart rate is an important risk factor for diabetes risk. The results suggest that novel treatment approaches targeting reduction of high heart rate for incidence of diabetes may be worth further investigation.     

Extrapolation for a pharmacokinetic model for acetaminophen from adults to neonates: A Latin Hypercube Sampling analysis

Physiological and drug-specific parameters need to be adjusted when extrapolating a pharmacokinetic (PK) model from adults to neonates, so as to reproduce the time profiles of the studied drug(s) consistent with clinical, in vivo data or in vitro cell line measurements. In this paper we present a parameter analysis method, i.e. the Latin Hypercube Sampling (LHS) method for an acetaminophen (APAP) PK model. The original model consists of two compartments (the blood and the urine) with Michaelis-Menten kinetic parameters determined for APAP and its metabolites. The physiological parameters are scaled through allometric laws from adults to neonates, and APAP-specific parameters are adjusted for enzymatic maturational changes. The LHS method is used to statistically investigate the interplay between these parameters. The results for the extrapolated APAP model are consistent with published APAP PK data in neonates. We found the sulphation clearance parameter played a crucial role in the neonatal PK model, but its influence was weakened if the volume of distribution parameters were included. We suggest that this kind of in silico experiment could be valuable as the first step in PK model extrapolation between different ages.     

Analytical chemistry,toxicology, epidemiology and health impact assessment of melamine in infant formula: Recent progress and developments

This review summarizes the most recent scientific literature and regulations regarding analytical chemistry, toxicology, epidemiology, exposure, and risk assessment of melamine in infant formula. For analyses, enzyme-linked immunosorbent assay, high-performance liquid chromatography, capillary electrophoresis, gas chromatography coupled with mass spectrometry and liquid chromatography coupled with tandem mass spectrometry have commonly been used. Organization of proficiency test programs provided good evidence to facilitate granting laboratories accreditation and to ascertain the measurement reliability of melamine methods. Metabolic studies demonstrated that melamine is predominantly restricted to blood or extracellular fluid and is not extensively distributed to organs and tissues. Studies of human renal histopathology and clinical diagnoses indicated that melamine-related obstructive nephropathy derives from melamine precipitation in the lower urinary tract, with stones that are thought to be melamine–uric acid complexes. Epidemiologic studies showed that the occurrence of melamine-related urolithiasis is related to both the concentration of melamine in ingested milk products and the duration of ingestion. Long-term follow-up cohort studies should be continued to further investigate the epidemic and chronic hazard of melamine-induced nephrotoxicity. The World Health Organization set a tolerable daily intake of 0.2 mg/kg bw/day to be applied to “the whole population including infants”. Other authorities and research institutes have set/proposed lower values.