Bin Peng

Age-related progression of arterial stiffness and its elevated positive association with blood pressure in healthy people

OBJECTIVEnArterial stiffness occurs as a consequence of age and arteriosclerosis, but the mechanics of the progression of arterial stiffness along with age is not fully explored. We aim to investigate the age-related progression of arterial stiffness through the examination of 4659 healthy subjects aged from 20 to 75.nnnMETHODSnThe cardio-ankle vascular index (CAVI) was used as a marker of arterial stiffness. Piecewise linear regression model was utilized to analyze the association between different stages of age and arterial stiffness. The mean CAVI values of age groups were calculated to fit the linear regression and curvilinear regression models. We also constructed multiple regression models to examine the interactions of blood pressure and age on CAVI.nnnRESULTnThe regression coefficients (β) of piecewise linear regression of each age group (<35, 35-44, 45-59, >59) were 0.07062, 0.03133, 0.03840 and 0.07272 for men, and 0.03342, 0.02025, 0.04826 and 0.10604 for women, respectively. The highest R square came from curvilinear regression for men (R(2)xa0=xa00.9220), and piecewise linear regression for women (R(2)xa0=xa00.9454). The interactions between each type of blood pressure and age were significant (all Pxa0<xa00.001).nnnCONCLUSIONnThere were various increased trends between different stages of age. Age-related progression of arterial stiffness could be better explained by a growth curve, rather than a straight line. In addition, blood pressure has an increasingly positive association with CAVI values as age increases.

An integrative framework for Bayesian variable selection with informative priors for identifying genes and pathways.

The discovery of genetic or genomic markers plays a central role in the development of personalized medicine. A notable challenge exists when dealing with the high dimensionality of the data sets, as thousands of genes or millions of genetic variants are collected on a relatively small number of subjects. Traditional gene-wise selection methods using univariate analyses face difficulty to incorporate correlational, structural, or functional structures amongst the molecular measures. For microarray gene expression data, we first summarize solutions in dealing with ‘large p, small n’ problems, and then propose an integrative Bayesian variable selection (iBVS) framework for simultaneously identifying causal or marker genes and regulatory pathways. A novel partial least squares (PLS) g-prior for iBVS is developed to allow the incorporation of prior knowledge on gene-gene interactions or functional relationships. From the point view of systems biology, iBVS enables user to directly target the joint effects of multiple genes and pathways in a hierarchical modeling diagram to predict disease status or phenotype. The estimated posterior selection probabilities offer probabilitic and biological interpretations. Both simulated data and a set of microarray data in predicting stroke status are used in validating the performance of iBVS in a Probit model with binary outcomes. iBVS offers a general framework for effective discovery of various molecular biomarkers by combining data-based statistics and knowledge-based priors. Guidelines on making posterior inferences, determining Bayesian significance levels, and improving computational efficiencies are also discussed.

Fetal and infant exposure to the Chinese famine increases the risk of fatty liver disease in Chongqing, China.

Early life exposure to the famine may affect the susceptibility to the metabolic disorders. The objective of this study was to examine the associations of early life exposure to the Chinese Famine (1959–1961) with the risk of fatty liver disease, obesity, hypertension, and hyperglycemia in adulthood.

HIV-related behaviors, social support and health-related quality of life among men who have sex with men and women (MSMW): a cross-sectional study in Chongqing, China.

Background Health-related quality of life (HRQOL) has become commonly used both as a concept and as a field of research. However, little is known about the HRQOL of men who have sex with men and women (MSMW). The aim of this study was to examine HIV-related behaviors, social support, and HRQOL status and explore its predictors among MSMW. Methods An anonymous cross-sectional study was conducted by snowball sampling method in 2013. A total of 563 Chinese MSM completed a structured questionnaire. The HRQOL and social support were measured with the Chinese version of the World Health Organization Quality of Life Scale (WHOQOL-BRFE) and the Social Support Rating Scale (SSRS), respectively. Results Of the 563 MSM analyzed, 77 (13.68%) were MSMW who had a higher proportion of in-marriage and preference for an insertive role as compared with the men who have sex with men only (MSMO) (P<0.05). As high as 70.13% of MSMW had no regular sex partners and 72.73% of MSMW reported engaging in unprotected anal sex in the last six months. 36.36% had tested for HIV, while only 12.99% had accepted HIV voluntary counseling and testing (VCT) services. The scores of objective support and subjective support in MSMW were significantly higher than that of MSMO (P<0.05). No statistically significant difference was found in scores of all the four domains of the HRQOL between MSMW and MSMO. When comparing the HRQOL scores of MSMW with the Chinese general population reference group, the scores of MSMW were significantly lower in physical health domain. In a multivariate regression model, age, monthly income, sexual role, VCT acceptability, subjective support were associated with variability in HRQOL. Conclusions To improve the HRQOL among MSMW, more attention needs to be paid to those with low social support, low-income, the old and those prefer a receptive role during anal sex populations.

Using Extreme Value Theory Approaches to Forecast the Probability of Outbreak of Highly Pathogenic Influenza in Zhejiang, China

Background Influenza is a contagious disease with high transmissibility to spread around the world with considerable morbidity and mortality and presents an enormous burden on worldwide public health. Few mathematical models can be used because influenza incidence data are generally not normally distributed. We developed a mathematical model using Extreme Value Theory (EVT) to forecast the probability of outbreak of highly pathogenic influenza. Methods The incidence data of highly pathogenic influenza in Zhejiang province from April 2009 to November 2013 were retrieved from the website of Health and Family Planning Commission of Zhejiang Province. MATLAB “VIEM” toolbox was used to analyze data and modelling. In the present work, we used the Peak Over Threshold (POT) model, assuming the frequency as a Poisson process and the intensity to be Pareto distributed, to characterize the temporal variability of the long-term extreme incidence of highly pathogenic influenza in Zhejiang, China. Results The skewness and kurtosis of the incidence of highly pathogenic influenza in Zhejiang between April 2009 and November 2013 were 4.49 and 21.12, which indicated a “fat tail” distribution. A QQ plot and a mean excess plot were used to further validate the features of the distribution. After determining the threshold, we modeled the extremes and estimated the shape parameter and scale parameter by the maximum likelihood method. The results showed that months in which the incidence of highly pathogenic influenza is about 4462/2286/1311/487 are predicted to occur once every five/three/two/one year, respectively. Conclusions Despite the simplicity, the present study successfully offers the sound modeling strategy and a methodological avenue to implement forecasting of an epidemic in the midst of its course.

Prevalence of High Arterial Stiffness and Gender-specific Differences in the Relationships with Classical Cardiovascular Risk Factors.

AIMnTo investigate the relationships between arterial stiffness and classic cardiovascular risk factors with respect to gender differences in addition to the prevalence of high arterial stiffness in Chongqing, China based on an examination of 18,336 subjects.nnnMETHODSnThe cardio-ankle vascular index was used as a marker of arterial stiffness. The relationships between arterial stiffness and body mass index (BMI) as well as metabolic syndrome (MetS) were estimated using logistic regression models.nnnRESULTSnThe prevalence of high arterial stiffness was 12.74% in men and 9.91% in women. For age and BMI, compared with the reference group, men had higher adjusted odds ratios (ORs) in each group versus their female counterparts. For each individual index of MetS, the effects of waist circumference and systolic blood pressure (SBP) on high arterial stiffness exhibited remarkable gender differences, with women having higher ORs and adjusted ORs than men. As the sum of MetS traits increased, the ORs and adjusted ORs in the subjects also increased, with women having higher values than men in each group.nnnCONCLUSIONSnGender-specific differences exist in the prevalence of high arterial stiffness among subjects compared by age, BMI and MetS, with varying effects of influence for these factors between genders.

Integrative Bayesian variable selection with gene-based informative priors for genome-wide association studies.

BackgroundGenome-wide Association Studies (GWAS) are typically designed to identify phenotype-associated single nucleotide polymorphisms (SNPs) individually using univariate analysis methods. Though providing valuable insights into genetic risks of common diseases, the genetic variants identified by GWAS generally account for only a small proportion of the total heritability for complex diseases. To solve this “missing heritability” problem, we implemented a strategy called integrative Bayesian Variable Selection (iBVS), which is based on a hierarchical model that incorporates an informative prior by considering the gene interrelationship as a network. It was applied here to both simulated and real data sets.ResultsSimulation studies indicated that the iBVS method was advantageous in its performance with highest AUC in both variable selection and outcome prediction, when compared to Stepwise and LASSO based strategies. In an analysis of a leprosy case–control study, iBVS selected 94 SNPs as predictors, while LASSO selected 100 SNPs. The Stepwise regression yielded a more parsimonious model with only 3 SNPs. The prediction results demonstrated that the iBVS method had comparable performance with that of LASSO, but better than Stepwise strategies.ConclusionsThe proposed iBVS strategy is a novel and valid method for Genome-wide Association Studies, with the additional advantage in that it produces more interpretable posterior probabilities for each variable unlike LASSO and other penalized regression methods.

Outcomes of sustained-release formulation of valproate and topiramate monotherapy in patients with epilepsy: a multi-centre, cohort study.

Background New-generation antiepileptic drugs (AEDs) tend to replace traditional AEDs as the first-line choice for epilepsy. However, whether this change results in better outcome, especially in China, remains unknown. Methodology/Principal Findings Two broad spectrum AEDs, the traditional drug of sustained-release formulation of valproate (SRVPA) and the new-generation drug of topiramate, were compared in patients with epilepsy as monotherapy in this multi-centre, observational cohort study from 2000 to 2011. The primary outcome was time to treatment failure. The secondary outcomes included time to first seizure, time to 12-month remission, and time to 24-month remission. Drug tolerability was assessed. Cox proportional hazard models (95% confidence interval [CI]) were used to analyse the relative risks expressed as hazard ratios (HR). Of the 1008 recruited patients, 519 received SRVPA and 489 received topiramate. SRVPA was better than topiramate (28.3% vs. 41.5%; HRu200a=u200a0.62, [95% CI 0.49–0.77]; p<0.0001) in primary outcome, and in time to first seizure (56.1% vs. 69.3%; HRu200a=u200a0.73, [95% CI 0.62–0.86]; pu200a=u200a0.0002). No significant difference was observed between two groups in time to 12-month remission (52.6% vs. 42.5%; HRu200a=u200a1.01, [95% CI 0.84–1.23]; pu200a=u200a0.88) and time to 24-month remission (34.7% vs. 25.2%; HRu200a=u200a1.11, [95% CI 0.88–1.42]; pu200a=u200a0.38). 36 patients (6.9%) in SRVPA group and 37 patients (7.6%) in topiramate group presented treatment failure associated with intolerable adverse events, there was no significant difference between the two groups (pu200a=u200a0.70). Conclusions The SRVPA is more suitable than topiramate for Chinese epileptic patients, and our results support the viewpoint that traditional AEDs should be the first-line choice for epilepsy rather than new-generation AEDs.

Serum uric acid and non-alcoholic fatty liver disease in non-obesity Chinese adults

BackgroundPrevious studies found elevated serum uric acid (SUA) was associated with the development or progression of non-alcoholic fatty liver disease (NAFLD) in general population; in this study we aim to investigate the association of SUA and the severity of NAFLD based on grade of fatty liver on ultrasonography in non-obese subjects.MethodsData were obtained from subjects via routine physical examinations in the Public Health Center of our hospital between 2011 and 2014. The data included completed anthropometry and blood biochemical indicators and the results of abdominal ultrasound. The diagnosis of NAFLD was according to the clinical diagnosis of the Guidelines for the diagnosis and treatment of nonalcoholic fatty liver disease in 2008.ResultsIn total, 95,924 subjects were analyzed in this study. The prevalence rate of lean-NAFLD was 8.16%, among which 7.58% had mild steatosis, and 0.58% had moderate and severe steatosis. The prevalence of fatty liver was increased progressively with SUA. Among which the prevalence of mild fatty liver from Q1 to Q4 were 10.33%, 18.39%, 23.11% and 25.93%; the prevalence of moderate and severe fatty liver from Q1 to Q4 were 1.06%, 2.82%, 5.05% and 7.27%. Lean-subjects with hyperuricemia had an OR of 1.718 (95% CI 1.622–1.820) to have NAFLD, after adjusted for other metabolic disorders. The area under curve (AUC) for detecting mild fatty liver based on SUA was 0.70; and the AUC for detecting moderate and severe fatty liver based on SUA was 0.78.ConclusionsOur data showed positive associations between elevated SUA levels and lean-NAFLD risk in the inland Chinese adults, independent of other metabolic factors. Our study also suggests that SUA could be considered as a simple and non-invasive method to follow up patients with lean-NAFLD.

Non‑small-cell lung cancer pathological subtype‑related gene selection and bioinformatics analysis based on gene expression profiles

Lung cancer is one of the most common malignant diseases and a major threat to public health on a global scale. Non-small-cell lung cancer (NSCLC) has a higher degree of malignancy and a lower 5-year survival rate compared with that of small-cell lung cancer. NSCLC may be mainly divided into two pathological subtypes, adenocarcinoma and squamous cell carcinoma. The aim of the present study was to identify disease genes based on the gene expression profile and the shortest path analysis of weighted functional protein association networks with the existing protein-protein interaction data from the Search Tool for the Retrieval of Interacting Genes. The gene expression profile (GSE10245) was downloaded from the National Center for Biotechnology Information Gene Expression Omnibus database, including 40 lung adenocarcinoma and 18 lung squamous cell carcinoma tissues. A total of 8 disease genes were identified using Naïve Bayesian Classifier based on the Maximum Relevance Minimum Redundancy feature selection method following preprocessing. An additional 21 candidate genes were selected using the shortest path analysis with Dijkstras algorithm. The AURKA and SLC7A2 genes were selected three and two times in the shortest path analysis, respectively. All those genes participate in a number of important pathways, such as oocyte meiosis, cell cycle and cancer pathways with Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. The present findings may provide novel insights into the pathogenesis of NSCLC and enable the development of novel therapeutic strategies. However, further investigation is required to confirm these findings.