Ying Lv

Vaspin promotes 3T3-L1 preadipocyte differentiation.

Vaspin, a novel adipocyte factor secreted from visceral adipose tissues, is associated with obesity and insulin resistance and can regulate glucose and lipid metabolism, increase insulin sensitivity, and suppress inflammation; however, the underlying mechanisms remain unknown. Proliferation and maladaptive differentiation are important pathological mechanisms underlying obesity. This study aimed to evaluate the effects of vaspin on the proliferation and differentiation of preadipocyte 3T3-L1 cells and to explore the likely mechanisms responsible for 3T3-L1 differentiation. Vaspin was added to cultured 3T3-L1 cells, and the differentiation of adipocytes was evaluated using Oil Red O staining. The AKT signaling pathway and specific differentiation factors related to the differentiation of preadipocyte 3T3-L1 cells, peroxisome proliferator-activated γ and the CCAAT/enhancer-binding protein (C/EBP) family, were evaluated using reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses during the early phase of differentiation. Additionally, adiponectin mRNA, interleukin-6 mRNA (IL-6 mRNA), and glucose transporter-4 (GLUT4) protein levels were measured in the differentiated adipocytes. The results indicated that vaspin promotes the intracellular accumulation of lipids and increases differentiation-related factors, including peroxisome proliferator-activated receptor γ, C/EBPα, and free fatty acid-binding protein 4 (FABP4), in a dose-dependent manner. Additionally, vaspin (200 ng/mL) increased the mRNA and protein levels of C/EBPβ, peroxisome proliferator-activated γ, C/EBPα, and FABP4. Moreover, compared with the control, significantly smaller eight-day differentiated adipocytes were observed, and these cells exhibited decreased IL-6 mRNA and increased GLUT4 mRNA levels; these results also indicated the potential of vaspin to promote the insulin-mediated AKT signaling pathway during the early phase of differentiation. In conclusion, vaspin is able to promote the differentiation of 3T3-L1 preadipocytes and may increase their sensitivity to insulin and suppress obesity.

Serum hepatitis B core antibody titer use in screening for significant fibrosis in treatment-naïve patients with chronic hepatitis B

Background Previous studies have revealed that hepatitis B core antibody (anti-HBc) levels vary throughout the different phases of treatment-naïve chronic hepatitis B (CHB) patients and can be used as a predictor of treatment response in both interferon-α and nucleoside analogue therapies. However, few data have been published regarding the relationship between quantitative anti-HBc (qAnti-HBc) levels and liver fibrosis in patients with CHB. Results A total of 489 HBeAg-positive (HBeAg (+)) and 135 HBeAg-negative (HBeAg (−)) patients were recruited. In both HBeAg (+) and HBeAg (−) groups, the S0−1/S0 subjects had significantly lower qAnti-HBc levels than the S2−4 subjects (p < 0.05). Multiple logistic regression analysis showed that the parameters for predicting significant fibrosis (S ≥ 2) included age, PLT and qAnti-HBc. In HBeAg (+) subjects, the AUROC of qAnti-HBc for predicting significant fibrosis was 0.734 (95% CI 0.689 to 0.778) and the optimal cut-off was 4.58 log10IU/mL, with a sensitivity of 63.08% and a specificity of 74.83%. In HBeAg (−) subjects, the AUROC was 0.707 (95% CI 0.612 to 0.801) and the optimal cut-off value was 4.37 log10IU/mL, with a sensitivity of 75.53% and a specificity of 56.10%. Materials and Methods From 2012 to 2015, we conducted a cross-sectional study of treatment-naïve CHB patients. Liver biochemistry, hepatitis B virus (HBV) serological markers, HBV DNA, hepatitis B surface antigen (HBsAg) titers and HBV genotype were determined using commercial assays, and serum qAnti-HBc levels were measured using double-sandwich immunoassay. Liver biopsies and serum samples were obtained on the same day. Conclusions The present study showed an association between high serum qAnti-HBc levels and significant fibrosis (S ≥ 2) in treatment-naïve CHB patients. Furthermore, we described a serum qAnti-HBc cut-off for predicting significant fibrosis in CHB patients infected with HBV genotype B or C.

L539 fs/47, a truncated mutation of human ether-a-go-go-related gene (hERG), decreases hERG ion channel currents in HEK 293 cells

Mutations in the human ether‐a‐go‐go‐related gene (hERG) are responsible for congenital Type 2 long QT syndrome (LQT2). Previously, we reported a truncated mutation of hERG in a Chinese family with LQT2, namely L539 fs/47, which is composed of a 19 bp deletion mutation and an A1692G polymorphism. This mutation was found to cause an LQT2 phenotype. The aim of the present study was to investigate the functional role of L539 fs/47 at the cellular level and its potential contribution to the loss of function of hERG channels. The function of the truncated mutation L539 fs/47 was evaluated by constructing a mutated plasmid, transfection of the mutated cDNA into HEK 293 cells and subsequent patch‐clamp, western blotting and immunostaining experiments. Homologous expression of L539 fs/47 in HEK 293 cells produced a non‐functional protein that was detected in cell membranes. When L539 fs/47 was expressed simultaneously with wild‐type hERG, it suppressed wild‐type hERG currents in a dose‐dependent manner and changed the gating properties of the channel. Although L539 fs/47 hERG proteins were detected on plasma membranes, they failed to generate hERG currents. In general, L539 fs/47 dose‐dependently decreases hERG ion channel currents and suppresses the function of wild‐type channels function. This may explain, in part, the clinical manifestations of LQT2 in the family with this mutation.

Hamilton rating scale for depression-24 (HAM-D24) as a novel predictor for diabetic microvascular complications in type 2 diabetes mellitus patients

The study was designed to investigate whether the hamilton rating scale for depression (24-items) (HAM-D24) can be used to predict the diabetic microvascular complications in type 2 diabetes mellitus (T2DM) patients. 288 hospitalized patients with T2DM were enrolled. Their diabetic microvascular complications including diabetic nephropathy, diabetic retinopathy, diabetic peripheral neuropathy and diabetic foot as well as demographic, clinical data, blood samples and echocardiography were documented. All the enrolled patients received HAM-D24 evaluation. The HAM-D24 score and incidence of depression in T2DM patients with each diabetic microvascular complication were significantly higher than those in T2DM patients without each diabetic microvascular complication. After the adjustment of use of insulin and hypoglycemic drug, duration of T2DM, mean platelet volume, creatinine, albumin, fasting glucose, glycosylated hemoglobin type A1C, left ventricular ejection fraction, respectively, HAM-D24 score was still significantly associated with diabetic microvascular complications (OR = 1.188-1.281, all P < 0.001). The AUC of HAM-D24 score for the prediction of diabetic microvascular complication was 0.832 (0.761-0.902). 15 points of HAM-D24 score was considered as the optimal cutoff with the sensitivity of 0.778 and specificity of 0.785. In summary, HAM-D24 score may be used as a novel predictor of diabetic microvascular complications in T2DM patients.

G-T haplotype established by rs3785889-rs16941382 in GOSR2 gene is associated with coronary artery disease in Chinese Han population

OBJECTIVES The aim of the present study is to assess the association between the human GOSR2 gene and coronary artery disease using a haplotype-based case-control study in Chinese Han population. METHODS A total of 283 coronary artery disease patients and 280 controls were genotyped for the human GOSR2 gene (rs197932, rs3785889, rs197922, rs17608766, and rs16941382). Data were analyzed for three separate groups: the total subjects, men, and women. RESULTS For the total subjects, the frequency of the G-T haplotype established by rs3785889-rs16941382 was significantly higher in the coronary artery disease patients as compared to the control subjects (P=0.009). Multiple logistic regression analysis also confirmed that the subjects with G-T haplotype established by rs3785889-rs16941382 (homozygote) were found having significantly higher chance suffering from coronary artery disease than the ones without this haplotype (OR=1.887, P=0.007). CONCLUSIONS The G-T haplotype established by rs3785889-rs16941382 may be a risk genetic marker for coronary artery disease patients in Chinese Han population.Objectives The aim of the present study is to assess the association between the human GOSR2 gene and coronary artery disease using a haplotype-based case-control study in Chinese Han population. Methods A total of 283 coronary artery disease patients and 280 controls were genotyped for the human GOSR2 gene (rs197932, rs3785889, rs197922, rs17608766, and rs16941382). Data were analyzed for three separate groups: the total subjects, men, and women. Results For the total subjects, the frequency of the G-T haplotype established by rs3785889-rs16941382 was significantly higher in the coronary artery disease patients as compared to the control subjects (P=0.009). Multiple logistic regression analysis also confirmed that the subjects with G-T haplotype established by rs3785889-rs16941382 (homozygote) were found having significantly higher chance suffering from coronary artery disease than the ones without this haplotype (OR=1.887, P=0.007). Conclusions The G-T haplotype established by rs3785889-rs16941382 may be a risk genetic marker for coronary artery disease patients in Chinese Han population.

Matrine‐Type Alkaloids Inhibit Advanced Glycation End Products Induced Reactive Oxygen Species‐Mediated Apoptosis of Aortic Endothelial Cells In Vivo and In Vitro by Targeting MKK3 and p38MAPK Signaling

Background The matrine‐type alkaloids are bioactive components extracted from Sophora flavescens, which is used in treatment of diabetes mellitus in traditional Chinese medicine. Advanced glycation end products mediate diabetic vascular complications. This study was aimed to investigate the protective effects and molecular mechanisms of matrine‐type alkaloids on advanced glycation end products–induced reactive oxygen species–mediated endothelial apoptosis. Methods and Results Rats aorta and cultured rat aortic endothelial cells were exposed to advanced glycation end products. Matrine‐type alkaloids, p38 mitogen‐activated protein kinase (MAPK) inhibitor, and small interference RNAs against p38 MAPK kinases MAPK kinase kinase (MKK)3 and MKK6 were administrated. Intracellular reactive oxygen species production, cell apoptosis, phosphorylation of MKKs/p38 MAPK, and expression levels of heme oxygenase/NADPH quinone oxidoreductase were assessed. The nuclear factor erythroid 2‐related factor 2 nuclear translocation and the binding activity of nuclear factor erythroid 2‐related factor 2 with antioxidant response element were also evaluated. Matrine‐type alkaloids suppressed intracellular reactive oxygen species production and inhibited endothelial cell apoptosis in vivo and in vitro by recovering phosphorylation of MKK3/6 and p38 MAPK, nuclear factor erythroid 2‐related factor 2 nuclear translocation, and antioxidant response element binding activity, as well as the expression levels of heme oxygenase/NADPH quinone oxidoreductase. p38 MAPK inhibitor treatment impaired the effects of matrine‐type alkaloids in vivo and in vitro. MKK3/6 silencing impaired the effects of matrine‐type alkaloids in vitro. Conclusions Matrine‐type alkaloids exert endothelial protective effects against advanced glycation end products induced reactive oxygen species–mediated apoptosis by targeting MKK3/6 and enhancing their phosphorylation.

Association between neutrophilic granulocyte percentage and depression in hospitalized patients with heart failure

BackgroundPrevious researches reveal that depression is associated with increased inflammatory markers. As a simple and cheap inflammatory marker, we hypothesize that neutrophilic granulocyte percentage is associated with depression in hospitalized heart failure patients, whose prevalence of depression is at a very high level.MethodsThree hundred sixty-six cases of hospitalized heart failure patients with left ventricular ejection fraction (LVEF) ≤45% and New York Heart Association (NYHA) class II-IV were enrolled. All the enrolled patients received Hamilton Rating Scale for Depression (24-items) (HAM-D24). The demographic, clinical data, blood samples and echocardiography were documented. The Pearson simple linear correlation was performed to evaluate the confounding factors correlated with HAM-D24 depression index. The significantly correlated factors were enrolled as independent variables in Logistic regression to determine the risk or protective factors for depression, which was taken as dependent variable.ResultsTwo hundred ten cases of hospitalized heart failure patients (57.4%) had depression. Among them, 134 patients (63.8%) had mild depression, 58 patients (27.6%) had moderate depression and 18 patients (8.6%) had severe depression. Pearson simple linear correlation revealed that in hospitalized patients with heart failure, the neutrophils granulocyte percentage was positively correlated with the HAM-D24 depression index (r = .435, p < .001). After the adjustment of age, BMI, number of members of the household, smoking index, New York Heart Association (NYHA) classification, hemoglobin, TC, LDL-C, creatinine, cystatin-C, TBIL and albumin, the neutrophils granulocyte percentage is still significantly associated with depression in hospitalized heart failure patients (OR = 1.046, p < .001).ConclusionsThe neutrophils granulocyte percentage may be used as a new marker for depression in hospitalized heart failure patients.

TCTAP C-007 Very Young Male Patient of Inferior Wall STEMI Caused by Excessive Consumption of Alcohol

### Patient Initials or Identifier Number 809756 ### Relevant Clinical History and Physical Exam A 26 years old young man was transferred from the local hospital diagnosed as inferior wall STEMI for 4 days. Severe chest pain occurred 4 days ago, after an excessive consumption of alcohol. In the

GW26-e2507 The Effect of Catheter-directed Thrombolysis with Low-dose Urokinase on Acute Lower Extremity limb Ischemia

To evaluate the safety and effectiveness of catheter-directed thrombolysis therapy with low-dose urokinase for acute lower extremity ischemia limb. Retrospective analysis of clinical data of 50 cases, including 27 males and 23 females, aged 27-81 years old, the onset time of 10 hours to 14 days,