PNPLA3 I148M variant in nonalcoholic fatty liver disease:Demographic and ethnic characteristics and the role of the variant in nonalcoholic fatty liver fibrosis

Patatin-like phospholipase domain-containing 3(PNPLA3 or adiponutrin) displays anabolic and catabolic activities in lipid metabolism,and has been reported to be significantly associated with liver fat content.Variousstudies have established a strong link between the 148 isoleucine to methionine protein variant(I148M) of PNPLA3 and liver diseases,including nonalcoholic fatty liver disease(NAFLD).However,detailed demographic and ethnic characteristics of the I148 M variant and its role in the development of nonalcoholic fatty liver fibrosis have not been fully elucidated.The present review summarizes the current knowledge on the association between the PNPLA3 I148 M variant and NAFLD,and especially its role in the development of nonalcoholic fatty liver fibrosis.First,we analyze the impact of demographic and ethnic characteristics of the PNPLA3 I148 M variant and the presence of metabolic syndrome on the association between PNPLA3 I148 M and NAFLD.Then,we explore the role of the PNPLA3 I148 M in the development of nonalcoholic fatty liver fibrosis,and hypothesize the underlying mechanisms by speculating a pro-fibrogenic network.Finally,we briefly highlight future research that may elucidate the specific mechanisms of the PNPLA3 I148 M variant in fibrogenesis,which,in turn,provides a theoretical foundation and valuable experimental data for the clinical management of nonalcoholic fatty liver fibrosis.

Development and external validation of models to predict acute respiratory distress syndrome related to severe acute pancreatitis

BACKGROUND Acute respiratory distress syndrome(ARDS)is a major cause of death in patients with severe acute pancreatitis(SAP).Although a series of prediction models have been developed for early identification of such patients,the majority are complicated or lack validation.A simpler and more credible model is required for clinical practice.AIM To develop and validate a predictive model for SAP related ARDS.METHODS Patients diagnosed with AP from four hospitals located at different regions of China were retrospectively grouped into derivation and validation cohorts.Statistically significant variables were identified using the least absolute shrinkage and selection operator regression method.Predictive models with nomograms were further built using multiple logistic regression analysis with these picked predictors.The discriminatory power of new models was compared with some common models.The performance of calibration ability and clinical utility of the predictive models were evaluated.RESULTS Out of 597 patients with AP,139 were diagnosed with SAP(80 in derivation cohort and 59 in validation cohort)and 99 with ARDS(62 in derivation cohort and 37 in validation cohort).Four identical variables were identified as independent risk factors for both SAP and ARDS:heart rate[odds ratio(OR)=1.05;95%CI:1.04-1.07;P<0.001;OR=1.05,95%CI:1.03-1.07,P<0.001],respiratory rate(OR=1.08,95%CI:1.0-1.17,P=0.047;OR=1.10,95%CI:1.02-1.19,P=0.014),serum calcium concentration(OR=0.26,95%CI:0.09-0.73,P=0.011;OR=0.17,95%CI:0.06-0.48,P=0.001)and blood urea nitrogen(OR=1.15,95%CI:1.09-1.23,P<0.001;OR=1.12,95%CI:1.05-1.19,P<0.001).The area under receiver operating characteristic curve was 0.879(95%CI:0.830-0.928)and 0.898(95%CI:0.848-0.949)for SAP prediction in derivation and validation cohorts,respectively.This value was 0.892(95%CI:0.843-0.941)and 0.833(95%CI:0.754-0.912)for ARDS prediction,respectively.The discriminatory power of our models was improved compared with that of other widely used models and the calibration ability and clinical utility of the prediction models performed adequately.CONCLUSION The present study constructed and validated a simple and accurate predictive model for SAPrelated ARDS in patients with AP.

Genetic association of COL1A1 polymorphisms with high myopia in Asian population: a Meta-analysis

AIM: To comprehensively evaluate the potential association of COL1A1 polymorphisms with high myopia by a systematic review and Meta-analysis. METHODS: All association studies on COL1A1 and high myopia reported up to June 10, 2014 in PubMed, Embase, Web of Science, and the Chinese Biomedical Database were retrieved. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were analyzed for single-nucleotide polymorphisms (SNPs) using fixed- and random - effects models according to between-study heterogeneity. Publication bias analyses were conducted by Eggers test. RESULTS: A total of four studies from reported papers were included in this analysis. The Meta-analyses for COL1A1 rs2075555, composed of 2304 high myopia patients and 2272 controls, failed to detect any significant association with high myopia. A total of 971 cases and 649 controls were tested for COL1A1 rs2269336. The association of COL1A1 rs2269336 with high myopia was observed in recessive model (CC vs CG+GG, P = 0.03) and in heterozygous model (CG vsGG, P = 0.04), but not in other models. CONCLUSION: This Meta-analysis shows that COL fill rs2269336 (CC vs CG +GG) affects individual susceptibility to high myopia, whereas there is no association detected between SNPs rs2075555 and high myopia. Given the limited sample size, further investigations including more ethnic groups are required to validate the association.

Inflammatory biomarkers and cerebral small vessel disease:a community-based cohort study

Background and purpose Although inflammation has been proposed to be a candidate risk factor for cerebral small vessel disease(CSVD),previous findings remain largely inconclusive and vary according to disease status and study designs.The present study aimed to investigate possible associations between inflammatory biomarkers and MRI markers of CSVD.Methods A group of 15 serum inflammatory biomarkers representing a variety of those putatively involved in the inflammatory cascade was grouped and assessed in a cross-sectional study involving 960 stroke-free subjects.The biomarker panel was grouped as follows:systemic inflammation(high-sensitivity C reactive protein(hsCRP),interleukin 6 and tumour necrosis factorα),endothelial-related inflammation(E-selectin,P-selectin,intercellular adhesion molecule 1,vascular cell adhesion molecule 1(VCAM-1),CD40 ligand,lipoprotein-associated phospholipase A2,chitinase-3-like 1 protein and total homocysteine(tHCY))and media-related inflammation(matrix metalloproteinases 2,3 and 9,and osteopontin).The association(s)between different inflammatory groups and white matter hyperintensity(WMH),lacunes,cerebral microbleeds(CMBs),enlarged perivascular space(PVS)and the number of deep medullary veins(DMVs)were investigated.Results High levels of serum endothelial-related inflammatory biomarkers were associated with both increased WMH volume(R^(2)=0.435,p=0.015)and the presence of lacunes(R^(2)=0.254,p=0.027).Backward stepwise elimination of individual inflammatory biomarkers for endothelial-related biomarkers revealed that VCAM-1 was significant for WMH(β=0.063,p=0.005)and tHCY was significant for lacunes(β=0.069,p<0.001).There was no association between any group of inflammatory biomarkers and CMBs or PVS.Systemic inflammatory biomarkers were associated with fewer DMVs(R^(2)=0.032,p=0.006),and backward stepwise elimination of individual systemic-related inflammatory biomarkers revealed that hsCRP(β=−0.162,p=0.007)was significant.Conclusion WMH and lacunes were associated with endothelial-related inflammatory biomarkers,and fewer DMVs were associated with systemic inflammation,thus suggesting different underlying inflammatory processes and mechanisms.

Association between large artery stenosis,cerebral small vessel disease and risk of ischemic stroke

We aimed to assess the associations of large artery stenosis(LAS)and cerebral small vessel disease(CSVD)with the risk of ischemic stroke and to investigate their respective and combined contributions.In the prospective population-based Shunyi Study,1,082 stroke-free participants aged 55.9±9.1 years were included.Participants were followed for incident stroke throughout the study period(2013-2019).Total small vessel disease score was used to measure CSVD burden.Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound.We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models.During a mean follow-up of 4.2 years,34 participants(3.1%)experienced at least one ischemic stroke.Severe LAS(≥50% stenosis versus no stenosis:HR=3.27(95%CI:1.31-8.18))and high CSVD burden(total small vessel disease score 2-4 versus 0 point:HR=12.73(4.83-33.53))were associated with increased stroke risk independently.In multivariate models,CSVD burden(7.72%)explained a larger portion of the variation in stroke risk than severity of LAS(3.49%).Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects,while those with high CSVD burden deserve more attention in primary prevention of stroke.

Metabolic syndrome, intracranial arterial stenosis and cerebral small vessel disease in community- dwelling populations

Background and purpose This study aimed to investigate the association of metabolic syndrome(MetS)with both intracranial atherosclerotic stenosis(ICAS)and imaging markers of cerebral small vessel disease(CSVD)in a community-based sample.Methods This study included 943 participants(aged 55.6±9.2 years,36.1%male)from the community-based Shunyi cohort study.MetS was defined according to the joint interim criteria and quantified by the MetS severity Z-score.ICAS was evaluated by brain magnetic resonance angiography.The MRI markers of CSVD,including white matter hyperintensities(WMHs),lacunes,cerebral microbleeds(CMBs)and enlarged perivascular spaces(EPVS),were assessed.Multiple regression models were used to investigate the association of MetS severity Z-score with ICAS and these CSVD markers.Results We found that risk of ICAS(OR=1.75,95%CI 1.39 to 2.21,p<0.001)increased consistently with MetS severity.MetS severity was significantly associated with higher risks of WMH volume(β=0.11,95%CI 0.01 to 0.20,p=0.02)and lacunes(OR=1.28,95%CI 1.03 to 1.59,p=0.03)but not the presence of CMBs(OR=0.93,95%CI 0.74 to 1.16,p=0.51)and PVS severity(EPVS in basal ganglia:OR=0.96,95%CI 0.84 to 1.09,p=0.51 and EPVS in white matter:OR=1.09,95%CI 0.96 to 1.23,p=0.21).Conclusions Our findings suggest that WMH and lacunes share risk factors with atherosclerosis of the cerebral artery,whereas the impact of glucose and lipid metabolic disorder to CMB or EPVS might be weak.

Prevalence of active and passive tobacco smoking among Beijing residents in 2011

Objectives: This study was aimed to investigate the prevalence of active and passive tobacco smoking among Beijing residents in 2011. Methods: A cross-sectional survey was conducted, using a stratified multistage cluster random sampling method to select a representative sample of 20,242, among Beijing residents aged 18-79 years. Active and passive tobacco smoking information was collected by a standardized and validated questionnaire in a face-to-face interview. All estimates of prevalence and numbers were weighted by the 2010 Beijing Population Census data and the sampling scheme. Results: Among Beijing residents aged 18-79 years, the overall prevalence of ever smokers and current smokers were 33.13%and 30.18%, respectively. The prevalence in males was much higher than that in females (60.75%vs. 3.75%for ever smokers, and 55.53% vs. 3.21% for current smokers, respectively). For overall current smokers, 14.12 cigarettes were consumed per day. However, only 8.91%of ever smokers quitted smoking at the time of the survey, and 2.44%of ever smokers quitted smoking in recent two years. Furthermore, 44.74%of overall nonsmokers and former smokers, with 47.03%of males and 43.63%of females, reported exposure to secondhand smoke for at least 15 minutes per day and at least one day per week. Conclusions: Tobacco smoking prevalence is still extremely high in Beijing. Nonsmokers do still suffer from secondhand smoke critically. Further urgent efforts for tobacco control are warranted in Beijing.