Identification of MicroRNAs as potential biomarkers for detecting ischemic stroke.

BACKGROUND: Increasing epidemic of ischemic stroke (IS) makes it urgent to understand the pathogenesis and regulatory mechanism, previous studies have described microRNAs (miRNAs) is part of the brain's response to ischemia. OBJECTIVE: The aim of this study was to screen potential biomarkers for the prediction and novel treatment of IS. METHODS: Differentially expressed miRNAs were screened from three newly diagnosed IS patients and three controls by RNA sequencing technology. Furthermore, target prediction databases were then used to analysis the target genes of different expressed miRNAs, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database were used to identify the functions and the main biochemical and signal pathways of differentially expressed target genes. RESULTS: Our results revealed that 27 miRNAs were differentially expressed in IS, among which, hsa-miR-659-5p was the most highly increased and was first found to be associated with IS. In addition, KEGG pathway analyses showed that differentially expressed miRNAs were mainly significantly enriched in lysosome pathway, cytokine-cytokine receptor interaction pathway, spliceosome pathway, base excision repair pathway. CONCLUSIONS: miRNAs were involved in IS pathogenesis, and hsa-miR-659-5p, hsa-miR-151a-3p and hsa-miR-29c-5p as the three highest |log2FoldChange| regulation in this study, which may be the biomarkers of IS and need further study.

Dysregulated lncRNA and mRNA may promote the progression of ischemic stroke via immune and inflammatory pathways: results from RNA sequencing and bioinformatics analysis.

BACKGROUND: Long non-coding RNAs (lncRNAs) are widely involved in gene transcription regulation and which act as epigenetic modifiers in many diseases. OBJECTIVE: To determine whether lncRNAs are involved in ischemic stroke (IS), we analyzed the expression profile of lncRNAs and mRNAs in IS. METHODS: RNA sequencing was performed on the blood of three pairs of IS patients and healthy controls. Differential expression analysis was used to identify differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs). Based on the co-expression relationships between lncRNA and mRNA, a series of bioinformatics analysis including GO and KEGG enrichment analysis and PPI analysis, were conducted to predict the function of lncRNA. RESULTS: RNA sequencing produced a total of 5 DElncRNAs and 144 DEmRNAs. Influenza A pathway and Herpes simplex infection pathway were the most significant pathways. EP300 and NFKB1 were the most important target proteins, and Human leucocyte antigen (HLA) family were the key genes in IS. CONCLUSIONS: Analysis of this study revealed that dysregulated lncRNAs in IS may lead to IS by affecting the immune and inflammation system.

High-Throughput Sequencing and Exploration of the lncRNA-circRNA-miRNA-mRNA Network in Type 2 Diabetes Mellitus.

OBJECTIVE: Long noncoding RNA (lncRNA) and circular RNA (circRNA) are receiving increasing attention in diabetes research. However, there are still many unknown lncRNAs and circRNAs that need further study. The aim of this study is to identify new lncRNAs and circRNAs and their potential biological functions in type 2 diabetes mellitus (T2DM). METHODS: RNA sequencing and differential expression analysis were used to identify the noncoding RNAs (ncRNAs) and mRNAs that were expressed abnormally between the T2DM and control groups. The competitive endogenous RNA (ceRNA) regulatory network revealed the mechanism of lncRNA and circRNA coregulating gene expression. The biological functions of lncRNA and circRNA were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The candidate hub mRNAs were selected by the protein-protein interaction (PPI) network and validated by using the Gene Expression Omnibus (GEO) database. RESULTS: Differential expression analysis results showed that 441 lncRNAs (366 upregulated and 75 downregulated), 683 circRNAs (354 upregulated and 329 downregulated), 93 miRNAs (63 upregulated and 30 downregulated), and 2923 mRNAs (1156 upregulated and 1779 downregulated) were identified as remarkably differentially expressed in the T2DM group. The ceRNA regulatory network showed that a single lncRNA and circRNA can be associated with multiple miRNAs, and then, they coregulate more mRNAs. Functional analysis showed that differentially expressed lncRNA (DElncRNA) and differentially expressed circRNA (DEcircRNA) may play important roles in the mTOR signaling pathway, lysosomal pathway, apoptosis pathway, and tuberculosis pathway. In addition, PIK3R5, AKT2, and CLTA were hub mRNAs screened out that were enriched in an important pathway by establishing the PPI network. CONCLUSIONS: This study is the first study to explore the molecular mechanisms of lncRNA and circRNA in T2DM through the ceRNA network cofounded by lncRNA and circRNA. Our study provides a novel insight into the T2DM from the ceRNA regulatory network.

Systematic Review and Meta-Analysis of -New-Generation Tyrosine Kinase Inhibitors versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia.

BACKGROUNDS: We performed this systematic review and meta-analysis to compare the efficacy of new-generation tyrosine kinase inhibitors (NG-TKIs; including dasatinib, nilotinib, bosutinib, radotinib, and ponatinib) versus imatinib for patients with newly diagnosed chronic myeloid leukemia (CML). SUMMARY: We identified randomized controlled trials comparing the efficacy of NG-TKIs versus imatinib as the first-line treatment for CML patients by searching the PubMed, Cochrane library, and EMBASE databases. Two reviewers independently extracted data and assessed study quality. A meta-analysis was performed to calculate risk ratios and 95% CIs using a fixed-effects model.Our study included 10 trials. Overall, treatment with NG-TKIs significantly improved the major molecular response and MR4.5 at all time points, and early molecular response at 3 months. Importantly, overall survival (OS) was significantly higher with the NG-TKIs at 12 months. Besides, NG-TKI-treated patients showed a significantly lower CML-related death and progression to the accelerated phase/blast crisis. Key Messages: In first-line treatment, NG-TKIs are superior to imatinib regarding OS at 12 months, and because molecular response rates were higher with the NG-TKIs at all time points, the NG-TKIs favor treatment-free remission.

Association between normal triglyceride and insulin resistance in US adults without other risk factors: a cross-sectional study from the US National Health and Nutrition Examination Survey, 2007-2014.

OBJECTIVE: Traditionally, the absence of insulin resistance risk factors (IRRFs) was considered a low risk for insulin resistance (IR). However, IR also existed in certain individuals without IRRFs; thus this study aims to explore predictors of IR targeted at the population without IRRFs. DESIGN: Cross-sectional survey. SETTING: National Health and Nutrition Examination Survey. PARTICIPANTS: Participants without regular IRRFs (IRRF-Free, n=2478) and a subgroup without optimal IRRFs (IRRF-Optimal, n=1414) were involved in this study. PRIMARY AND SECONDARY OUTCOME MEASURE: IRRFs and the optimal cut-off value of triglyceride (TG) to predict IR. RESULTS: Overall, the prevalence of IR was 6.9% and 5.7% in the IRRF-Free group and the IRRF-Optimal group, respectively. TG and waist circumference were independently associated with the prevalence of IR in both the groups (OR=1.010 to 10.20; p<0.05 for all), where TG was positively associated with IR. The area under the receiver operating characteristic curve of TG was 0.7016 (95% CI: 0.7013 to 0.7018) and 0.7219 (95% CI: 0.7215 to 0.7222), and the optimal cut-off value of TG to predict IR was 79.5 mg/dL and 81.5 mg/dL in the IRRF-Free group and the IRRF-Optimal group, respectively. CONCLUSION: There is an association between TG and IR even in the normal range of TG concentration. Therefore, normal TG could be used as an important indicator to predict the prevalence of IR in the absence of IRRFs.

Epidemiological analysis of respiratory and intestinal infectious diseases in three counties of Sichuan: the baseline survey of Disaster Mitigation Demonstration Area in western China.

BACKGROUND: Natural disasters can indirectly induce epidemics of infectious diseases through air and water pollution, accelerated pathogen reproduction, and population migration. This study aimed to explore the epidemiological characteristics of the main infectious diseases in Sichuan, a province with a high frequency of natural disasters. METHODS: Data were collected from the local Centers for Disease Control infectious disease reports from Lu, Shifang and Yuexi counties from 2011 to 2015 and from the baseline survey of the Disaster Mitigation Demonstration Area in Western China in 2016. Principal component regression was used to explore the main influencing factors of respiratory infectious diseases (RIDs). RESULTS: The incidence rates of RIDs and intestinal infectious diseases (IIDs) in 2015 were 78.99/100,000, 125.53/100,000, 190.32/100,000 and 51.70/100,000, 206.00/100,000, 69.16/100,000 in Lu, Shifang and Yuexi respectively. The incidence rates of pulmonary tuberculosis (TB) was the highest among RIDs in the three counties. The main IIDs in Lu and Shifang were hand-foot-mouth disease (HFMD) and other infectious diarrhea; however, the main IIDs in Yuexi was bacillary dysentery. The proportions of illiterate and ethnic minorities and per capita disposable income were the top three influencing factors of RIDs. CONCLUSIONS: TB was the key point of RIDs prevention among the three counties. The key preventable IIDs in Lu and Shifang were HFMD and other infectious diarrhea, and bacillary dysentery was the major IIDs in Yuexi. The incidence rates of RIDs was associated with the population composition, the economy and personal hygiene habits.

The associations between smoking and obesity in northeast China: a quantile regression analysis.

Obesity is a risk factors of chronic diseases, and smoking is associated with both chronic diseases and obesity. There were some controversies about the associations between smoking and obesity. Thus, our study aimed to explore the associations of smoking with obesity, using body mass index (BMI) and waist circumference (WC) as obesity indices in northeast China. We enrolled a sample of 16,412 participants in Jilin province aged 18-79 in this study, which were derived from a cross-sectional survey in 2012. We used quantile regression (QR) models to identify the associations of smoking with obesity in different quantiles of BMI (or WC) by genders. The differences of BMI and WC by genders were statistically significant (p < 0.05). In conclusion, compared with current non-smokers, current smokers had lower BMI but higher WC. As increasing of WC, the association of WC with smoking was getting stronger, especially in females.

Analysis of Influencing Factors of Poststroke Depression: Is Higher Body Mass Index Always a Risk Factor of Poststroke Depression?

Poststroke depression (PSD) is a common complication of stroke. We sought to investigate the influencing factors of PSD and explored the association between body mass index (BMI) and PSD. A total of 397 stroke patients in a hospital in Qiqihar City, China, were included in this study in 2016. The order of independent variable importance was the score of the National Institute of Health Stroke Scale, frequency of stroke, age, BMI, and sleep duration. Sleep duration of 7 hours or more (compared with <7 hours) was negatively associated with the Self-Rating Depression Scale (SDS) score in all quantiles. BMI of 28.0 kg/m or more (compared with 24.0-28.0 kg/m) was negatively associated with SDS score, and the coefficients manifested a continuous increasing trend from P30 to P84.1 in patients aged 65 years or more. In addition, the relationship between BMI and SDS score demonstrated a "U"-shaped curve in patients aged less than 65 years. The National Institute of Health Stroke Scale score, the frequency of stroke, sleep duration, and BMI were the influencing factors of PSD. BMI played different roles in the two age groups.

Weighted Gene Coexpression Network Analysis Identified MicroRNA Coexpression Modules and Related Pathways in Type 2 Diabetes Mellitus.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a metabolic disease with high incidence, which has seriously affected human life and health. MicroRNA, a short-chain noncoding RNA, plays an important role in T2DM. Identification of meaningful microRNA modules and the role of microRNAs provide a basis for searching potential biomarkers of T2DM. MATERIALS AND METHODS: In this study, three newly diagnosed patients with T2DM and three controls were selected for Whole Peripheral Blood RNA Sequencing to establish a microRNA library. Weighted gene coexpression network analysis (WGCNA) was applied to construct coexpression modules and to detect the trait-related microRNA modules; then, KEGG enrichment analysis was performed to predict the biological function of the interest modules, and candidate hub microRNAs were screened out by the value of module membership (MM) and protein-protein interaction (PPI) network. RESULT: Four microRNA modules (blue, brown, magenta, and turquoise) were highly associated with the T2DM; the number of miRNAs in these modules ranged from 41 to 469. The Fc gamma R-mediated phagocytosis pathway, Rap1 signaling pathway, MAPK signaling pathway, and Lysosome pathway were common pathways in three of the four modules. RPS27A, UBC, and RAC1 were the top three proteins in our study; their corresponding RNAs were miR-1271-5p, miR-130a-3p, miR-130b-3p, and miR-574-3p. CONCLUSION: In summary, this study identified blood miRNAs in human T2DM using RNA sequencing. The findings may be the foundation for understanding the potential role of miRNAs in T2DM.

Associations of dietary patterns with hypertension among adults in Jilin Province, China: a structural equation modelling approach.

OBJECTIVE: To explore the direct and indirect associations of dietary patterns with hypertension using structural equation modelling (SEM). DESIGN: Factor analysis with varimax rotation was used to classify different dietary patterns and SEM was employed to investigate the associations of dietary patterns with hypertension. Total cholesterol to HDL-cholesterol (TC:HDL-C) ratio and LDL-cholesterol to HDL-cholesterol (LDL-C:HDL-C) ratio were used as observed indicator variables of the lipid latent variable. Waist circumference, body fat percentage and BMI, which were associated with hypertension, were used as observed indicator variables of the obesity latent variable. SETTING: International Chronic Disease Cohort (ICDC) that began in 2005 with the purpose of describing the frequency and determinants of chronic diseases in Jilin Province, China. PARTICIPANTS: A total of 1492 adults (40-79 years) were enrolled in the baseline study from August 2010 to August 2011. RESULTS: Hypertension prevalence in our study population was 34·9 %. It was found that the wine pattern, condiment pattern, obesity latent variable, lipid latent variable, glucose, age and family history of hypertension were factors that had an association with hypertension via SEM, and the corresponding coefficients were 0·056, 0·011, 0·230, 0·281, 0·098, 0·232 and 0·116, respectively. CONCLUSIONS: The wine pattern and lipid latent variable had positive direct associations with hypertension. The condiment pattern had a positive indirect association with hypertension via the obesity latent variable. The vegetables pattern, modern pattern and snack pattern were not associated with hypertension.

The Influencing Factors of Serum Lipids among Middle-aged Women in Northeast China.

BACKGROUND: Dyslipidemia is a common and serious health problem, especially in middle-aged women. We aimed to reveal quantile-specific associations of serum lipids [triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c) and high density lipoprotein cholesterol (HDL-c)] with influencing factors in middle-aged women. METHODS: A sample of 5635 participants were enrolled from Jilin, China, in 2012. Quantile regression (QR) model was performed to identify factors which influenced serum lipids in different quantiles. RESULTS: The influencing factors of TG, TC, LDL-c and HDL-c were different. Waist circumference (WC), menopause, smoking, diabetes and hypertension were positively associated with TG in almost all quantiles; Menopause and age were positively associated with TC in almost all quantiles. WC, living in urban areas and alcohol consumption were positively associated with TC in low and middle quantiles, diabetes was positively associated with TC from P50 to P95. The result of LDL-c was similar to TC; BMI was negatively associated with HDL-c from P50 to P90. WC and diabetes were negatively associated with HDL-c from P5 to P90. CONCLUSION: Among middle-aged women, menopause, diabetes and WC were the main factors affecting the serum lipids. Postmenopausal women would get more risk in increasing the level of serum lipids.

Association of Blood Pressure with Fasting Blood Glucose Levels in Northeast China: A Cross-Sectional Study.

Hypertension and diabetes mellitus (DM) have become major public health issues, and previous studies have shown that there is an association between hypertension and DM. However, there is a lack of detailed information about this association. This study aimed to explore how different blood pressure (BP) levels were associated with fasting blood glucose (FBG) levels. A cross-sectional survey with adults aged 18 to 79 years was conducted in Jilin Province, China in 2012. Lambda-mu-sigma (LMS) was used to preliminarily explore the associations of BP with FBG. Quantile regression (QR) was performed to identify the specific associations by adjusting for confounding factors. The distributions of systolic blood pressure (SBP) (χ2 = 710.76, P < 0.001) and diastolic blood pressure (DBP) (χ2 = 460.20, P < 0.001) were different according to gender. LMS showed that the associations of BP with FBG became stronger when the FBG levels were close to 5.6 mmol/L. QR showed that FBG was positively associated with SBP (P30 to P90) and DBP (P20 to P90) in males. In females, FBG was positively associated with SBP from only P85 to P90. In summary, FBG was positively associated with BP in a gender-dependent manner.

A Study on the Factors Influencing Triglyceride Levels among Adults in Northeast China.

Triglyceride (TG) abnormalities are the most prevalent type of dyslipidaemia in the people of northeast China. Many researchers have investigated the prevalence, treatment and control of TG abnormalities, but little is known about the associations between the TG values and the factors that influence TG levels. This study aims to reveal quantile-specific associations of TG with its risk factors. A sample of 16,340 participants in Jilin Province were included in this study. A quantile regression (QR) model was performed to identify the factors that affected TG levels in different quantiles. The distribution of TG levels was different between males and females (χ 2 = 155.77, P < 0.001). Body mass index (BMI) and waist circumference (WC) were positively associated with TG levels in all quantiles. Drinking was positively associated with TG levels in high quantiles (P70.6 to P95) only in males, while age had a positive association with TG levels in all quantiles only in females. The risk of WC on TG levels was higher with increasing TG levels, and smokers were more at risk for increasing TG levels, as well.

Associations of Fasting Blood Glucose with Influencing Factors in Northeast China: A Quantile Regression Analysis.

Background: Diabetes mellitus (DM) has become a major public health problem in China. Although a number of researchers have investigated DM risk factors, little is known about the associations between values of fasting blood glucose (FBG) and influencing factors. This study aims to explore these associations by the quantile regression (QR) model. Methods: A cross-sectional survey based on a sample of 23,050 adults aged 18 to 79 years was conducted in Jilin in 2012, and some subjects were excluded due to missing values with respect to necessary variables or having glycemic control, in accordance with the purposes of this study. Finally, in total 14,698 people were included in this study. QR was performed to identify the factors influencing the level of FBG in different quantiles of FBG. Results: The distribution of FBG status was different between males and females (χ² = 175.30, p < 0.001). The QR model provided more detailed views on the associations of FBG with different factors and revealed apparent quantile-related patterns separately for different factors. Body mass index (BMI) was positively associated with the low and middle quantiles of FBG. Waist circumference (WC) had a positive association with the high quantiles of FBG. Conclusions: FBG had a positive association with BMI in normal FBG, and a positive association with WC in high FBG. Diet and alcohol intake were associated with FBG in normal FBG. FBG was more likely to be elevated in the elderly, female workers, and people with family history of DM.

Associations of Blood Pressure with the Factors among Adults in Jilin Province: A Cross-Sectional Study Using Quantile Regression Analysis.

Hypertension has become a major public health challenge. However, numerous research results reported in the literature focus primarily on risk factors of hypertension, little is known about how the whole continuum of blood pressure (BP) is associated with risk factors of hypertension. This study aims to reveal quantile-specific associations of BP with its risk factors. A cross-sectional survey based on a sample of 23,050 adults aged 18 to 79 years was conducted in Jilin Province in 2012, and some subjects were excluded due to missing values in BP or having BP control according to the purpose of this study. Quantile regression (QR) was employed to investigate the associations between systolic/diastolic blood pressure (SBP/DBP) and the risk factors. The SBP and DBP in males presented statistically higher than females (P < 0.001). High-salt diet for males manifested a slightly increasing positive association with higher SBP only for high quantiles (≥70), but with a higher DBP for middle part of the quantiles (30~75), compared with bland diet. High-salt diet, drinking and high-density lipoprotein cholesterol (HDL-C) were positively associated with BP measures in males. And the coefficient of total cholesterol (TC) in QR increased with BP in females who used to live in town.