Search

Epicardial movement during diastole is inversely proportional to myocardial stiffness but systolic regional thickening cannot precisely identify ischemic territories. The aim of the present study was to test the hypothesis that a correlation may be present between M-mode echocardiography parameters and poor outcomes in patients with heart failure and preserved ejection fraction. Patients with known cardiovascular disease were included in the test group (n=1,244) and patients without known cardiovascular disease were included in the control group (n=1,952). Patient records of routine measurements, M-mode echocardiography and mortality were collected. The control population and test population had the same left ventricular end-diastolic dimension (P=0.062) and left ventricular end-diastolic volume (P=0.053). A lower mitral flow velocity (P<0.05), higher Tei index (P<0.0001) and reduced distribution of diastolic wall strain (P<0.0001) were reported in the test populations compared with the control population. Patients of the test population with lower diastolic wall strain (<0.28) demonstrated a higher mortality rate than those with higher diastolic wall strain (≥0.28; P<0.0001) at the 3-year follow-up. M-mode echocardiographic parameters may be of use for predicting poor outcomes in patients with heart failure and preserved ejection fraction. [ABSTRACT FROM AUTHOR]

Camptothecin (CPT) and its derivative have been revealed to possess special anti-cancer activity, extraction methods are necessary for trace determination of CPTs in complex samples. In this work, we prepared a high efficient boronic acid-based polymer monolithic layer for microextraction of CPTs. A disposable membrane filter-based extraction device was developed, and boronic acid groups were co-polymerized into a polyporous polymer skeleton and served as the monolithic sorbent. The prepared poly(4-VB-MA-TRIM) showed good stability and great extraction efficiency toward four CPTs. After optimization of extraction conditions, poly(4-VB-MA-TRIM)-based solid-phase microextraction was coupled HPLC for determination of CPTs in biological samples. The method exhibited low limits of detection of 0.05–0.2 ng mL −1 , which is significantly more sensitive than reported HPLC methods. The method also showed wide linear range (0.1–100 and 0.5–200 ng mL −1 ), good linearity ( R 2 ≥ 0.9981) and good reproducibility (RSD ≤3.76%). The method has been applied in plasma samples, with good selectivity and good recoveries ranging from 85.1 to 104.7%. [ABSTRACT FROM AUTHOR]

Sleep problem among undergraduate students has become one of the most pressing public health problems. This study aimed to explore the latent class of sleep patterns and the factors affecting sleep in Chinese students of medical university. 3423 students participated in the cross-sectional study. The survey consisted of the reduced Morningness-Evening Questionnaire, the Pittsburgh Sleep Quality Index, and Health-Promoting Lifestyle Profile-II. Latent profile analysis and multinominal logistic regression analysis were performed. Three potential sleep categories were identified: "sleep disorder group" (1.87 %), "daytime dysfunction group" (24.42 %), and "good sleep group" (73.71 %). Compared with the "good sleep group," the "sleep disorder group" showed monthly living expenses (RMB) ≥ 3000 yuan (OR) = 13.04), interpersonal relationships as poor (OR = 3.71), health status as poor (OR = 45.09), circadian rhythm as eveningness (OR = 6.17), and poor health-promoting lifestyles (OR = 2.090) as its risk factors (all p < 0.05). Meanwhile, sophomore (OR = 1.75), junior (OR = 1.52), interpersonal relationships as poor (OR = 1.88), health status as poor (OR = 4.62), intermediate-chronotype (OR = 2.19), eveningness chronotype (OR = 5.66), and health-promoting lifestyles as poor (OR = 1.55) were identified as risk factors for the "daytime dysfunction group" (all p < 0.05). C ausal conclusions can not be drawn and recall bias in data collection. Significant population heterogeneity was found in the sleep quality. Implementing targeted interventions focusing on circadian rhythm and lifestyle is crucial to improve the sleep quality of students with different conditions. • Research on sleep quality in Chinese undergraduate of medical university was limited. • Our study was the first to explore their sleep quality patterns and influence factors. • Three categories (sleep disorder; daytime dysfunction; good sleep) were identified. • Sleep disorders and daytime dysfunction were each related with five different factors. [ABSTRACT FROM AUTHOR]

Current anti-rheumatic drugs are primarily modulating immune cell activation, yet their effectiveness remained suboptimal. Therefore, novel therapeutics targeting alternative mechanisms, such as synovial activation, is urgently needed. To explore the role of Midline-1 (Mid1) in synovial activation. NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice were used to establish a subcutaneous xenograft model. Wild-type C57BL/6, Mid1 -/-, Dpp4 -/-, and Mid1 -/- Dpp4 -/- mice were used to establish a collagen-induced arthritis model. Cell viability, cell cycle, qPCR and western blotting analysis were used to detect MH7A proliferation, dipeptidyl peptidase-4 (DPP4) and Mid1 levels. Co-immunoprecipitation and proteomic analysis identified the candidate protein of Mid1 substrates. Ubiquitination assays were used to determine DPP4 ubiquitination status. An increase in Mid1, an E3 ubiquitin ligase, was observed in human RA synovial tissue by GEO dataset analysis, and this elevation was confirmed in a collagen-induced mouse arthritis model. Notably, deletion of Mid1 in a collagen-induced arthritis model completely protected mice from developing arthritis. Subsequent overexpression and knockdown experiments on MH7A, a human synoviocyte cell line, unveiled a previously unrecognized role of Mid1 in synoviocyte proliferation and migration, the key aspects of synovial activation. Co-immunoprecipitation and proteomic analysis identified DPP4 as the most significant candidate of Mid1 substrates. Mechanistically, Mid1 promoted synoviocyte proliferation and migration by inducing ubiquitin-mediated proteasomal degradation of DPP4. DPP4 deficiency led to increased proliferation, migration, and inflammatory cytokine production in MH7A, while reconstitution of DPP4 significantly abolished Mid1-induced augmentation of cell proliferation and activation. Additionally, double knockout model showed that DPP4 deficiency abolished the protective effect of Mid1 defect on arthritis. Overall, our findings suggest that the ubiquitination of DPP4 by Mid1 promotes synovial cell proliferation and invasion, exacerbating synovitis in RA. These results reveal a novel mechanism that controls synovial activation, positioning Mid1 as a promising target for therapeutic intervention in RA. [Display omitted] [ABSTRACT FROM AUTHOR]

The risk of cardiovascular diseases is closely related to diabetes. Macrovascular disease is the main cause of death and disability in patients with type 2 diabetes. In recent years, the glucagon-like peptide-1 receptor agonist (GLP-1RA), a new type of hypoglycemic drug, has been shown to regulate blood sugar levels, improve myocardial ischemia, regulate lipid metabolism, improve endothelial function, and exert a protective role in the cardiovascular system. This study reviewed the protective effects of GLP-1RA on the cardiovascular system. [ABSTRACT FROM AUTHOR]

• Exendin-4 intervention led to a significant reduction in aortic plaques and body weight in ApoE-/- mice compared to the model group. • Exendin-4 significantly increased the proportion of myeloid-derived suppressor cells (MDSCs) in bone marrow and peripheral blood, while reducing pro-inflammatory cytokines (TNF-α, IFN-γ, IL-6) and increasing anti-inflammatory cytokines (TGF-β, IL-10) in both spleen and plasma. • Exendin-4 regulated lipid levels by decreasing triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), while increasing high-density lipoprotein cholesterol (HDL-C) in ApoE-/- mice. To investigate the impact of the glucagon-like peptide-1 (GLP-1) receptor agonist Exendin-4 on the proportion of myeloid-derived suppressor cells (MDSCs) in male ApoE-/- mice, and investigate alterations in the concentrations of inflammatory factors in plasma and spleen tissues and assess their correlation with MDSCs. Thirty male ApoE-/- mice were randomly divided into five groups (n = 6 per group): control group (CON), model group (MOD), Exendin-4 intervention group (MOD/Ex-4), Exendin-9-39 intervention group (MOD/Ex-9-39), and Exendin-4 + Exendin-9-39 combined intervention group (MOD/Ex-4 + Ex-9-39). After 4 weeks of drug intervention, changes in aortic plaque were observed using Oil Red O staining and H&E staining. Flow cytometry was employed to detect the content of myeloid-derived suppressor cells (MDSCs) in bone marrow and peripheral blood. ELISA was utilized to measure the concentrations of inflammatory factors in mouse peripheral blood plasma, while RT-qPCR was employed to quantify the expression levels of inflammatory factors in the spleen. Pearson correlation analysis was conducted to assess the relationship between MDSCs and inflammatory factors. Mice in the MOD group had significantly higher body weight compared to the CON group, with a statistically significant difference (P<0.05). Following Exendin-4 intervention, body weight was reduced compared to the MOD group (P<0.05). Additionally, Exendin-4 treatment led to a significant reduction in atherosclerotic plaque compared to the MOD group (P<0.001). After Exendin-4 intervention, the proportion of MDSCs in the bone marrow was higher than in the MOD group (P<0.001), and the proportion of MDSCs in peripheral blood was significantly higher than in the MOD group (P<0.05). Further investigation revealed that Exendin-4 could regulate lipid levels in mice, decreasing concentrations of TG (P<0.01), TC (P<0.0001), and LDL-C (P<0.0001), while increasing HDL-C concentrations (P<0.01). Moreover, after Exendin-4 treatment, the level of the cytokine IL-6 in peripheral plasma was significantly lower compared to the MOD group (P<0.0001), while levels of IL-10 and TGF-β were significantly higher compared to the MOD group (P<0.0001). In the spleen, levels of the cytokines IL-10 (P<0.0001) and TGF-β (P<0.001) were significantly increased compared to the MOD group. Pearson correlation analysis showed that the proportion of MDSCs in peripheral blood was positively correlated with IL-10 and TGF-β levels in both the spleen and peripheral blood. Additionally, the proportion of MDSCs in the bone marrow was positively correlated with IL-10 and TGF-β levels in the spleen and peripheral blood. Exendin-4 alleviates the severity of atherosclerosis. This process may be achieved by promoting the secretion of myeloid-derived suppressor cells (MDSCs) in the bone marrow and peripheral blood of atherosclerotic ApoE-/- mice, regulating the ratio of inflammatory factors in the body, reducing mouse body weight, and lowering blood lipids. [ABSTRACT FROM AUTHOR]

Aims. To investigate the effect of GLP-1/GLP-1R on the polarization of macrophages in the occurrence and development of atherosclerosis. Methods. Totally, 49 patients with coronary heart disease (CHD) and 52 cases of health control (HC) were recruited, all subjects accept coronary angiography gold standard inspection. One or more major coronary arteries (LM, LAD, LCx, and RCA) stenosis degree in 50% of patients as CHD group; the rest of the stenosis less than 50% or not seen obvious stenosis are assigned to the HC group. Flow cytometry were used to detect the percentage of (CD14+) M macrophages, (CD14+CD80+) M1 macrophages, (CD14+CD206+) M2 macrophages, and their surface GLP-1R expression differences in the two groups, using BD cytokine kit to detect the levels of IL-8, IL-1β, IL-6, IL-10, TNF, and IL-12p70. Results. GLP-1R expression on the surface of total macrophages and M2 macrophages was different between the CHD group and the HC group (P < 0.05). There was no difference in the percentage of total, M1 or M2 macrophages (P > 0.05). Concentration of IL-8 in the HC group was higher than that in the CHD group (P < 0.05). There is no significant difference in the cytokine IL-1β, IL-6, IL-10, TNF, and IL-12p70 in the two groups (P > 0.05). After controlling for potential confounders including age, gender, smoking status (S.S.), drinking status (D.S.), HR, SBP, DBP, PP, TC, TG, HDL-C, LDL-C, GHbA1c, M, M1, M2, GLP-1R_M, GLP-1R_M1, GLP-1R_M2, IL-8, IL-1β, IL-6, IL-10, TNF, and IL-12p70 by multiple linear regression, decreasing Gensini Score was significantly associated with increased percentage of M1 macrophage. Conclusion. GLP-1R agonist is independent of the hypoglycemic effect of T2DM and has protective effect on cardiovascular system. GLP-1R may regulate the polarization of macrophages toward M2, thus playing a protective role in the progression of coronary atherosclerosis. [ABSTRACT FROM AUTHOR]

Cohort studies found blood lipid traits were associated with the risk of chronic kidney disease (CKD). We aimed to investigate whether blood lipid traits were causally associated with the risk of CKD in the Chinese. 15,244 participants without kidney disease and cancer from the Dongfeng-Tongji cohort were recruited in 2008–2010 in Shiyan City, China. Blood total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglyceride (TG) levels were measured. 5251 participants had genotype data and were included in the Mendelian randomization analysis. Incident CKD was defined as estimated glomerular filtration rate <60 ml/min per 1.73 m2 in 2013. Logistic regression and Mendelian randomization methods were used to estimate the observed and causal associations of blood lipid traits with incident CKD. Various blood lipid traits were associated with CKD risk, and the odds ratios (95% confidence intervals) for incident CKD comparing the extreme quartiles were 1.45 (1.24–1.70) for TG, 1.26 (1.08–1.46) for nonHDL-c, 2.21 (1.91–2.57) for TC:HDL-c ratio, 2.14 (1.83–2.51) for TG:HDL-c ratio, and 0.47 (0.40–0.55) for HDL-c. The Mendelian randomization analysis indicated that 1 mmol/l increase in the genetic predicted blood TG level was associated with a 5% (95% confidence interval, 0–10%) higher risk of CKD. Although blood levels of HDL-c, TG, nonHDL-c, TC:HDL-c ratio, and TG:HDL-c ratio were observed to be associated with incident CKD, the Mendelian randomization analysis provided genetic evidence to support causal relation for blood TG level only. Image 1 • Whether blood lipid is causally related to the risk of chronic kidney disease (CKD), especially in the Chinese, is unclear. • The relation of blood lipid with the risk of CKD was prospectively investigated in 15,244 Chinese. • The top quartile of blood TG was related to a 45% higher risk of CKD compared with the bottom quartile. • Blood nonHDL-c, HDL-c, TC:HDL-c, and TG:HDL-c were related to the risk of CKD. • Mendelian randomization showed 1 mmol/l increase in blood TG was related to a 5% higher risk of CKD. [ABSTRACT FROM AUTHOR]

[Display omitted] • Whole-body or T cell-specific deletion of JAK2 completely prevented EAE onset. • JAK1/2 inhibitor baricitinib alleviated EAE severity. • Selective JAK2 inhibitor fedratinib alleviated EAE severity. • Genetic deletion or pharmacological inhibition of JAK2 reduced T H 1 differentiation. • JAK2 promoted T H 1 polarization via STAT5/T-bet signaling. Multiple sclerosis (MS) has been considered as a T cell-mediated autoimmune disease. However, the signaling pathways regulating effector T cells in MS have yet to be elucidated. Janus kinase 2 (JAK2) plays a crucial role in hematopoietic/immune cytokine receptor signal transduction. Here, we tested the mechanistic regulation of JAK2 and the therapeutic potential of pharmacological JAK2 inhibition in MS. Both inducible whole-body JAK2 knockout and T cell-specific JAK2 knockout completely prevented the onset of experimental autoimmune encephalomyelitis (EAE), a widely used MS animal model. Mice with JAK2 deficiency in T cells exhibited minimal demyelination and minimal CD45+ leukocyte infiltration in the spinal cord, accompanied by a remarkable reduction of T helper cell type 1 (T H 1) and type 17 (T H 17) in the draining lymph nodes and spinal cord. In vitro experiments showed that disruption of JAK2 markedly suppressed T H 1 differentiation and IFNγ production. The phosphorylation of signal transducer and activator of transcription 5 (STAT5) was reduced in JAK2 deficient T cells, while STAT5 overexpression significantly increased T H 1 and IFNγ production in STAT5 transgenic mice. Consistent with these results, JAK1/2 inhibitor baricitinib or selective JAK2 inhibitor fedratinib attenuated the frequencies of T H 1 as well as T H 17 in the draining lymph nodes and alleviated the EAE disease activity in mice. Our findings suggest that overactive JAK2 signaling in T lymphocytes is the culprit in EAE, which may serve as a potent therapeutic target for autoimmune disease. [ABSTRACT FROM AUTHOR]

• Previous studies have focused more on the role of MDSCs in diseases such as tumors, and this review comprehensively summarizes the role of MDSCs in the field of cardiovascular diseases. • The latest literature was reviewed to describe the source, phenotype, and immunosuppressive function of MDSCs. • Comprehensively summarizes the research progress of MDSCs in common cardiovascular diseases such as atherosclerosis, acute coronary syndrome, hypertension, myocarditis, heart failure, and dilated cardiomyopathy. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population found in the bone marrow, peripheral blood, and tumor tissue. Their role is mainly to inhibit the monitoring function of innate and adaptive immune cells, which leads to the escape of tumor cells and promotes tumor development and metastasis. Moreover, recent studies have found that MDSCs are therapeutic in several autoimmune disorders due to their strong immunosuppressive ability. Additionally, studies have found that MDSCs have an important role in the formation and progression of other cardiovascular diseases, such as atherosclerosis, acute coronary syndrome, and hypertension. In this review, we will discuss the role of MDSCs in the pathogenesis and treatment of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic studies have found that moderate alcohol consumption was associated with a decreased risk of coronary heart disease (CHD) incidence. Nevertheless, whether the drinking pattern is associated with CHD incidence still remains inconclusive. Methods: We included 8,469 Chinese men aged 45–81 years, who were free of CHD, stroke, or cancer at baseline from Dongfeng-Tongji cohort. A semi-structured questionnaire was used to collect information on alcohol consumption and other covariates. Cox proportional hazard regression model was applied to estimate the multivariable-adjusted hazard rations (HRs) and 95% confidence intervals (95% CIs). Results: During an average of 4.36 years of follow-up, we identified 959 incident CHD events. Compared with non-drinkers, the multivariable-adjusted HR (95% CI) of CHD incidence was 0.84 (0.71–0.98) in current drinkers. With respect to drinking pattern, men who consumed 20.01–40 grams ethanol once a time had a 24% lower risk of incident CHD (HR = 0.76, 95% CI = 0.62, 0.94) compared with non-drinkers. The adjusted HRs (95% CI) of CHD incidence were 0.80 (0.65, 0.99), 1.02 (0.84, 1.22), and 0.75 (0.59–0.96) in subjects who consumed 0.01–10, 10.01–30, and > 30 grams ethanol per day, respectively. Participants who consumed 20.01–40 grams ethanol per time with less than 5 times per week had the lowest risk of CHD incidence (HR = 0.73, 95% CI = 0.52, 0.96). No significant associations were observed between type or frequency of alcohol consumption and CHD incidence. Conclusions: Drinking was associated with a lower risk of CHD incidence in middle-aged and older Chinese men and moderate quantity of ethanol amounts once a time with lower frequency could been considered as a healthy drinking pattern, which might modify the relationship between alcohol consumption and incident CHD. [ABSTRACT FROM AUTHOR]

Background In prospective studies, relationship of serum uric acid (SUA) with risk of coronary heart disease (CHD) incidence is inconsistent. We evaluated the association of SUA with incident CHD and the potential modifying effect of major CHD risk factors related to SUA among a middle aged and elderly Chinese population. Methods We included 16, 063 participants who were free of CHD, stroke, cancer and renal diseases at baseline from Sep. 2008 to June 2010, and were followed until Oct. 2013. Cox proportional hazard model was used to estimate the hazard ratios (HR) and 95% confidence interval (95% CI) of CHD incidence in relation to SUA. Results The adjusted HR for incident CHD increased gradually with the increasing SUA levels ( P for linear trend = 0.005), and the HR across sex-specific SUA quartile was 1.26 (95% CI: 1.09, 1.47), 1.13 (95% CI: 0.97, 1.31), 1.23 (95% CI: 1.06, 1.43) and 1.00 (reference; P for trend = 0.014), respectively. In particular, the association was more evident in individuals with normal-weight and those without hypertension or metabolic syndrome (all P for interactions < 0. 05). Conclusions These findings suggested that higher SUA levels were independently associated with a dose-response increased risk of CHD incidence. [ABSTRACT FROM AUTHOR]

Background: Metabolomics studies in Caucasians have identified a number of novel metabolites in association with the risk of type 2 diabetes (T2D). However, few prospective metabolomic studies are available in Chinese populations. In the present study, we sought to identify novel metabolites consistently associated with incident T2D in two independent cohorts of Chinese adults.Methods: We performed targeted metabolomics (52 metabolites) of fasting plasma samples by liquid chromatography-mass spectrometry in two prospective case-control studies nested within the Dongfeng-Tongji (DFTJ) cohort and Jiangsu Non-communicable Disease (JSNCD) cohort. After following for 4.61 ± 0.15 and 7.57 ± 1.13 years, respectively, 1039 and 520 eligible participants developed incident T2D in these two cohorts, and controls were 1:1 matched with cases by age (± 5 years) and sex. Multivariate conditional logistic regression models were constructed to identify metabolites associated with future T2D risk in both cohorts.Results: We identified four metabolites consistently associated with an increased risk of developing T2D in the two cohorts, including alanine, phenylalanine, tyrosine and palmitoylcarnitine. In the meta-analysis of two cohorts, the odds ratios (95% confidence intervals, CIs) comparing extreme quartiles were 1.79 (1.32-2.42) for alanine, 1.91 (1.41-2.60) for phenylalanine, 1.85 (1.37-2.48) for tyrosine and 1.63 (1.21-2.20) for palmitoylcarnitine (all Ptrend ≤ 0.01).Conclusions: We confirmed the association of alanine, phenylalanine and tyrosine with future T2D risk and further identified palmitoylcarnitine as a novel metabolic marker of incident T2D in two prospective cohorts of Chinese adults. Our findings might provide new aetiological insight into the development of T2D. [ABSTRACT FROM AUTHOR]

Cytokines play a critical role in the pathogenesis and development of cardiovascular diseases. However, data linking cytokines to risk and severity of acute coronary syndrome (ACS) are still limited. We measured plasma profile of 280 cytokines using a quantitative protein microarray in 12 ACS patients and 16 healthy controls, and identified 15 differentially expressed cytokines for ACS. Osteopontin, chemokine ligand 23, brain derived neurotrophic factor and C-reactive protein (CRP) were further validated using immunoassay in two independent case-control studies with a total of 210 ACS patients and 210 controls. We further examined their relations with incident ACS among 318 case-control pairs nested within the Dongfeng-Tongji cohort, and found plasma osteopontin and CRP concentrations were associated with incident ACS, and the multivariable-adjusted odds ratio (95% confidence interval) was 1.29 (1.06–1.57) per 1-SD increase for osteopontin and 1.30 (1.02–1.66) for CRP, respectively. Higher levels of circulating osteopontin were also correlated with higher severity of ACS, and earlier ACS onset time. Adding osteopontin alone or in combination with CRP modestly improved the predictive ability of ACS beyond the Framingham risk scores. Our findings suggested that osteopontin might be a biomarker for incident ACS, using osteopontin adds moderately to traditional cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

This corrects the article DOI: 10.1038/srep24353 [ABSTRACT FROM AUTHOR]

Plasma lipid levels are important risk factors for cardiovascular disease and are influenced by genetic and environmental factors. Recent genome wide association studies (GWAS) have identified several lipid-associated loci, but these loci have been identified primarily in European populations. In order to identify genetic markers for lipid levels in a Chinese population and analyze the heterogeneity between Europeans and Asians, especially Chinese, we performed a meta-analysis of two genome wide association studies on four common lipid traits including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) in a Han Chinese population totaling 3,451 healthy subjects. Replication was performed in an additional 8,830 subjects of Han Chinese ethnicity. We replicated eight loci associated with lipid levels previously reported in a European population. The loci genome wide significantly associated with TC were near DOCK7, HMGCR and ABO; those genome wide significantly associated with TG were near APOA1/C3/A4/A5 and LPL; those genome wide significantly associated with LDL were near HMGCR, ABO and TOMM40; and those genome wide significantly associated with HDL were near LPL, LIPC and CETP. In addition, an additive genotype score of eight SNPs representing the eight loci that were found to be associated with lipid levels was associated with higher TC, TG and LDL levels (P = 5.52×10-16, 1.38×10-6 and 5.59×10-9, respectively). These findings suggest the cumulative effects of multiple genetic loci on plasma lipid levels. Comparisons with previous GWAS of lipids highlight heterogeneity in allele frequency and in effect size for some loci between Chinese and European populations. The results from our GWAS provided comprehensive and convincing evidence of the genetic determinants of plasma lipid levels in a Chinese population. [ABSTRACT FROM AUTHOR]

Background:High carbohydrate antigen 125 (CA-125) level was reported to be associated with some cardiac dysfunctions, such as chronic heart failure, but the relationship between CA-125 level and coronary heart disease (CHD) risk remains unclear. The aim of this study was to explore the potential association in a Chinese older population. Methods:In a population-based case-control study conducted in a Chinese older population, serum CA-125 levels were measured in 1177 diagnosed CHD patients and 3531 age and sex matched control subjects without CHD. Results:Serum CA-125 level was significantly higher in CHD patients than controls (P < 0.001) with adjustment for age, gender, smoking, drinking, BMI, physical activity, hypertension, dyslipidemia, diabetes mellitus, medication history and family history of CHD and myocardial infarction. CHD risk was doubled (OR: 2.10, 95%CI: 1.69-2.60) among subjects in the highest quartile compared to those in the lowest quartile of CA-125 level (Ptrend < 0.001). Furthermore, CA-125 levels were associated with CHD risks in subjects with age over 60 years (OR: 2.19, 95%CI: 1.75-2.73), current smokers (OR: 2.29, 95%CI: 1.50-3.49), current drinkers (OR: 2.35, 95%CI: 1.57-3.53) and subjects with hypertension (OR: 2.04, 95%CI: 1.71-2.43). Conclusions:Elevated serum CA-125 level might be associated with increased risk of coronary heart disease in the Chinese older population. Further investigations are needed to identify the possible biological role of CA-125 in CHD development in the future. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease is associated with obesity and insulin resistance. Factors that regulate the disposal of hepatic triglycerides contribute to the development of hepatic steatosis. G0/G1 switch gene 2 (G0S2) is a target of peroxisome proliferator-activated receptors and plays an important role in regulating lipolysis in adipocytes. Therefore, we investigated whether G0S2 plays a role in hepatic lipid metabolism. Adenovirus-mediated expression of G0S2 (Ad-G0S2) potently induced fatty liver in mice. The liver mass of Ad-G0S2-infected mice was markedly increased with excess triglyceride content compared to the control mice. G0S2 did not change cellular cholesterol levels in hepatocytes. G0S2 was found to be co-localized with adipose triglyceride lipase at the surface of lipid droplets. Hepatic G0S2 overexpression resulted in an increase in plasma Low-density lipoprotein (LDL)/Very-Low-density (VLDL) lipoprotein cholesterol level. Plasma High-density lipoprotein (HDL) cholesterol and ketone body levels were slightly decreased in Ad-G0S2 injected mice. G0S2 also increased the accumulation of neutral lipids in cultured HepG2 and L02 cells. However, G0S2 overexpression in the liver significantly improved glucose tolerance in mice. Livers expressing G0S2 exhibited increased 6-(N-(7-nitrobenz-2-oxa-1-3-diazol-4-yl) amino)-6-deoxyglucose uptake compared with livers transfected with control adenovirus. Taken together, our results provide evidence supporting an important role for G0S2 as a regulator of triglyceride content in the liver and suggest that G0S2 may be a molecular target for the treatment of insulin resistance and other obesity-related metabolic disorders. [ABSTRACT FROM AUTHOR]