CHA2DS2-VASc score as a prognostic indicator in patients with atrial fibrillation undergoing coronary stenting.

BACKGROUND: Patients with atrial fibrillation (AF) and coronary stenting had a poor prognosis. This study aimed to assess the accuracy of CHA2DS2-VASc score for predicting and grading adverse clinical outcomes in this population. METHODS: We reviewed the clinical data of all patients with previously documented nonvalvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. The study population was divided into three groups: 1) Low CHA2DS2-VASc score, ≦ 2 points, 2) Intermediate score, 3-4 points, and 3) High score, ≧ 5 points. Major adverse cardiac/cerebrovascular events (MACCE) were defined as a composite of all-cause death, nonfatal myocardial infarction, repeat revascularization and ischemic stroke/systemic thromboembolism (IS/SE). RESULTS: A total of 2394 patients (men: 72.3% vs. women: 27.7%, median age: 67 years) were included, with the CHA2 DS2-VASc score of 3.6 ± 1.6. The median follow-up duration was 36.2 months. All-cause mortality increased 3 folds from the low score (4.8%) to the high score group (15.8%). The high score group had more IS/SE (7.4%) and MACCE (26.3%). The CHA2 DS2-VASc score ≧ 5 points was independently associated with all-cause death (hazard ratio [HR]: 2.303, 95% confidence interval [CI]: 1.492- 3.555), IS/SE (HR: 4.169, 95% CI: 2.216-7.845) and MACCE (HR: 1.468, 95% CI: 1.113-1.936) on multivariate Cox proportional hazards regression. The area under the receiver operating characteristic curve of the CHA2DS2-VASc score was 0.644 (95% CI: 0.624-0.663) for all-cause death, 0.647 (95% CI: 0.627-0.666) for IS/SE, and 0.592 (95% CI: 0.572-0.611) for MACCE. DISCUSSION: CHA2DS2-VASc score was a reliable prognostic indicator in patients with AF and coronary stenting.

Vitamin B6 inhibits macrophage activation to prevent lipopolysaccharide-induced acute pneumonia in mice.

Macrophage activation participates in the pathogenesis of pulmonary inflammation. As a coenzyme, vitamin B6 (VitB6) is mainly involved in the metabolism of amino acids, nucleic acids, glycogen and lipids. We have previously reported that activation of AMP-activated protein kinase (AMPK) produces anti-inflammatory effects both in vitro and in vivo. Whether VitB6 via AMPK activation prevents pulmonary inflammation remains unknown. The model of acute pneumonia was induced by injecting mice with lipopolysaccharide (LPS). The inflammation was determined by measuring the levels of interleukin-1 beta (IL-1ß), IL-6 and tumour necrosis factor alpha (TNF-α) using real time PCR, ELISA and immunohistochemistry. Exposure of cultured primary macrophages to VitB6 increased AMP-activated protein kinase (AMPK) Thr172 phosphorylation in a time/dose-dependent manner, which was inhibited by compound C. VitB6 downregulated the inflammatory gene expressions including IL-1ß, IL-6 and TNF-α in macrophages challenged with LPS. These effects of VitB6 were mirrored by AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR). However, VitB6 was unable to inhibit LPS-induced macrophage activation if AMPK was in deficient through siRNA-mediated approaches. Further, the anti-inflammatory effects produced by VitB6 or AICAR in LPS-treated macrophages were abolished in DOK3 gene knockout (DOK3-/- ) macrophages, but were enhanced in macrophages if DOK3 was overexpressed. In vivo studies indicated that administration of VitB6 remarkably inhibited LPS-induced both systemic inflammation and acute pneumonia in wild-type mice, but not in DOK3-/- mice. VitB6 prevents LPS-induced acute pulmonary inflammation in mice via the inhibition of macrophage activation.

Up-regulation of paired-related homeobox 2 promotes cardiac fibrosis in mice following myocardial infarction by targeting of Wnt5a.

Cardiac fibrosis is a key factor to determine the prognosis in patient with myocardial infarction (MI). The aim of this study is to investigate whether the transcriptional factor paired-related homeobox 2 (Prrx2) regulates Wnt5a gene expression and the role in myocardial fibrosis following MI. The MI surgery was performed by ligation of left anterior descending coronary artery. Cardiac remodelling was assessed by measuring interstitial fibrosis performed with Masson staining. Cell differentiation was examined by analysis the expression of alpha-smooth muscle actin (α-SMA). Both Prrx2 and Wnt5a gene expressions were up-regulated in mice following MI, accompanied with increased mRNA and protein levels of α-SMA, collagen I and collagen III, compared to mice with sham surgery. Adenovirus-mediated gene knock down of Prrx2 increased survival rate, alleviated cardiac fibrosis, decreased infarction sizes and improved cardiac functions in mice with MI. Importantly, inhibition of Prrx2 suppressed ischaemia-induced Wnt5a gene expression and Wnt5a signalling. In cultured cardiac fibroblasts, TGF-ß increased gene expressions of Prrx2 and Wnt5a, and induced cell differentiations, which were abolished by gene silence of either Prrx2 or Wnt5a. Further, overexpression of Prrx2 or Wnt5a mirrored the effects of TGF-ß on cell differentiations of cardiac fibroblasts. Gene silence of Wnt5a also ablated cell differentiations induced by Prrx2 overexpression in cardiac fibroblasts. Mechanically, Prrx2 was able to bind with Wnt5a gene promoter to up-regulate Wnt5a gene expression. In conclusions, targeting Prrx2-Wnt5a signalling should be considered to improve cardiac remodelling in patients with ischaemic heart diseases.

Long-term effect of exercise on improving fatty liver and cardiovascular risk factors in obese adults: A 1-year follow-up study.

Exercise training can reduce hepatic fat accumulation and cardiovascular risk among patients with non-alcoholic fatty liver disease (NAFLD), but how long these benefits extend beyond the period of active intervention is unclear. Intrahepatic triglyceride (IHTG) content, measured by proton magnetic resonance spectroscopy, and metabolic risk factors among 220 obese people with NAFLD, who were randomly assigned to vigorous/moderate exercise, moderate exercise or no exercise (control), were assessed at 1 year after the 12-month exercise intervention. IHTG content was significantly reduced in the 2 exercise groups compared with the control group over the 12-month active intervention. It was significantly lower (by -2.39%) in the vigorous/moderate exercise group compared with the control group at the 1-year follow-up (95% confidence interval -4.72 to -0.05%; P = .045). Waist circumference and blood pressure remained significantly lower in the vigorous/moderate exercise group and the moderate exercise group compared with the control group at the 1-year follow-up. Visceral adipose fat remained significantly reduced, but with no differences among 3 groups. These findings suggest 12-month exercise intervention induced reductions in hepatic fat accumulation, abdominal obesity and blood pressure for up to 1 year after the active intervention, with some attenuation of the benefits.

Serum alanine aminotransferase independently correlates with intrahepatic triglyceride contents in obese subjects.

BACKGROUND AND AIM: Liver enzymes including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) are well recognized as surrogate makers reflecting non-alcoholic fatty liver disease (NAFLD). However, the associations of serum ALT, AST and GGT with hepatic lipid contents are not well established. The aim of this study was to investigate the relationship between liver enzymes and intrahepatic triglyceride (IHTG) contents, and explore the feasibility in using liver enzymes to reflect accumulation of IHTG in obese subjects. METHODS: A cross-sectional analysis was conducted in 475 obese adults aged 40-65 years. Anthropometric parameters and blood biochemical indexes including liver enzymes, glucose and lipid profiles were measured. The liver triglyceride contents of subjects were determined by (1)H-MRS. RESULTS: Serum ALT, AST and GGT were positively correlated with IHTG contents (p < 0.01). Serum ALT, AST and GGT levels at the highest quartile of IHTG contents were significantly elevated as compared with those in the lowest quartile (p < 0.01). Multivariate linear regression analysis demonstrated that serum ALT, but not AST or GGT was independently associated with IHTG contents. By logistic regression analysis, the odds ratio for higher IHTG contents was increased by 1.464 times/1 SD increase in serum ALT level after adjusting for multiple confounding factors [OR (95% CI) 2.464 (1.584-3.834)]. However, these relationships could not be observed between serum AST or GGT with IHTG contents. CONCLUSIONS: Serum ALT level is independently correlated with the hepatic triglyceride contents in obese subjects and more appropriate to be used as a predictor for the degree of NAFLD rather than AST and GGT.

Irisin is inversely associated with intrahepatic triglyceride contents in obese adults.

BACKGROUND & AIMS: Obesity is closely related to non-alcoholic fatty liver disease (NAFLD), which has become an important public health problem because of its high prevalence and association with metabolic syndromes. Irisin was recently identified as a novel peptide to improve obesity and glucose homeostasis, and considered to be therapeutic for human metabolic diseases. The aim of this study was to examine the association of serum irisin concentration and liver triglyceride contents in obese Chinese adults. METHODS: Serum irisin levels were measured and liver fat contents determined by (1)H MRS in 296 obese adults. Anthropometric parameters and blood biochemical indexes including liver enzymes, glucose, and lipid profiles were detected. The liver triglyceride contents of subjects were measured by (1)H MRS. The protein levels of irisin were determined by quantitative ELISA. RESULTS: We found that serum irisin levels were reduced in obese adults with NAFLD. By dividing the distribution of intrahepatic triglyceride (IHTG) contents into quartiles, serum irisin levels were reduced gradually with the increase of IHTG contents (p<0.01). Higher serum irisin levels were associated with preferable TG levels. Serum ALT and AST concentrations were inversely correlated with serum irisin levels. Multivariate linear regression analysis demonstrated that serum irisin levels were independently associated with liver fat (p<0.01). By logistic regression analysis, the odds ratio for higher IHTG contents was reduced by 12.4% per 1 SD increase in serum irisin concentrations after adjustment for multivariate metabolic factors [OR (95% CI); 0.876 (0.777-0.987)]. CONCLUSIONS: These results demonstrated that serum irisin concentrations were inversely associated with the triglyceride contents in the liver and liver enzymes in obese Chinese adults.

Predictive models for adverse clinical outcomes in Chinese patients with atrial fibrillation undergoing percutaneous coronary intervention with stenting.

OBJECTIVE: This study aimed to evaluate predictors for adverse cardiovascular outcomes in patients with atrial fibrillation (AF) undergoing coronary stenting. METHODS: We retrospectively recruited consecutive patients with previously documented non-valvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. Major adverse cardiac/cerebrovascular events (MACCE) were a composite of all-cause death, non-fatal myocardial infarction, repeat revascularization, and ischaemic stroke/systemic thromboembolism (IS/STE). Major bleeding referred to grade 2 or higher of Bleeding Academic Research Consortium criteria. RESULTS: A total of 2394 patients (men: 72.3% vs. women: 27.7%, median age: 67 years) were included. The CHA2DS2-VASc and HAS-BLED were 3.6 ± 1.6 and 1.9 ± 0.7, respectively. The median follow-up duration was 36.2 months. There were 230 (9.6%) deaths, 96 (4.0%) IS/STE, 426 (17.8%) MACCE, and 72 (3.0%) major bleeding. Multivariate Cox regression yielded predictive models for (1) all-cause death: diabetes, prior myocardial infarction, chronic kidney disease (CKD), ST-segment elevation myocardial infarction (STEMI) at presentation, heart failure, no use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and statins; (2) IS/STE: advanced age, prior history of ischaemic stroke and intracranial haemorrhage; (3) MACCE: prior history of myocardial infarction and ischaemic stroke, CKD, STEMI, heart failure, and no statin use; (4) major bleeding: prior major bleeding, prior myocardial infarction, CKD and use of oral anticoagulants. CONCLUSION: Chinese patients with AF and coronary stenting had high mortality and incidence of MACCE. We compiled separate predictive models for all-cause death, IS/STE, MACCE, and major bleeding.

[Sensitivity of new reagents for laboratory monitoring of low molecular weight heparin: an in vitro study].

OBJECTIVE: To explore the sensitivity of new activated clotting time (ACT) reagent for laboratory monitoring of low molecular weight heparin (LMWH). METHODS: Blood samples were collected from 30 healthy volunteers and different doses of LMWH (dalteparin) added. The dalteparin concentration of final blood samples was 0.1 - 1.8 U/ml. ACT and clot rate (CR) were measured with traditional reagent kaolin and new reagent magbar. Linear regression analysis was performed and a regression equation established between different dalteparin concentrations and their corresponding ACT and CR values. RESULTS: With rising dalteparin concentrations, the ACT values became gradually extended and the CR values were gradually reduced by both kaolin and magbar. Analysis of dose-response curves was obtained in vitro. And an excellent linear relationship was observed between the ACT and dalteparin concentrations for two reagents (P < 0.01). An exponential relationship was observed between the CR and dalteparin concentrations (P < 0.01). Differences in slope of regression curves of ACT were observed with the tested reagents (magbar 1097.6 s/U vs kaolin 59.3 s/U, P < 0.01). CONCLUSION: This in vitro study has shown that the sensitivity of new ACT test reagent (magbar) is good for laboratory monitoring of dalteparin. The new reagent magbar may be used for bedside monitoring of anticoagulant activity of LMWH.

Sex difference in clinical outcomes of Chinese patients with atrial fibrillation and coronary stenting according to age.

OBJECTIVE: Sex differences in the clinical outcomes of patients with atrial fibrillation (AF) and coronary stenting should be assessed according to age. METHODS: We analyzed the clinical data of all patients with nonvalvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. RESULTS: A total of 2,146 patients (71.8% men and 28.2% women) were included in the study. The mean age of the patients was 66.6±9.4 years. Women in this study were older and had higher prevalence of hypertension, diabetes, chronic kidney disease (CKD), and anemia. Smoking history was found to be higher in men, and women were less likely to be current smokers. The mean follow-up duration was 39.7 months. Women younger than 65 years had a remarkably higher mortality (11.2% vs. 5.3%, p=0.012) and a significantly lower rate of repeat revascularization (1.6% vs. 6.3%, p=0.034) than men. Female gender remained an independent predictor for all-cause mortality [hazard ratio (HR)=2.03, 95% confidence interval (CI): 1.09-3.79, p=0.025], along with heart failure (HR=3.64, 95% CI: 2.02-6.57, p<0.001) and CKD (HR=2.46, 95% CI: 1.09-5.57, p=0.031) after multivariate regression analysis. No significant difference was noted between men and women with regard to mortality, ischemic events, and major bleeding in elderly patients. CONCLUSION: In Chinese patients younger than 65 years with AF and coronary stenting, female gender was independently associated with increased mortality; men were more likely to receive repeat revascularization possibly due to the current smoking. Whether it was a biological difference or a recognition disparity of the disease between men and women warrants further investigation.

Association between the ferritin level and risk of gestational diabetes mellitus: A meta-analysis of observational studies.

AIMS/INTRODUCTION: The relationship between ferritin and the risk of gestational diabetes mellitus (GDM) has not been established. Thus, we carried out a meta-analysis based on the current literature. MATERIALS AND METHODS: We searched relevant databases on Embase, PubMed, Cochrane Library and Web of Science before 10 May 2019 to determine the relationship between ferritin and the risk of GDM. The relative risks and 95% confidence intervals of GDM risk were summarized using a random effects model. Studies using categories of ferritin as exposure were combined by dose-response analysis. We carried out both linear and non-linear trends. We also carried out subgroup analysis, whether or not the studies adjusted for potential confounders, and meta-regression analysis to explore the source of heterogeneity. Sensitivity analysis was carried out to explore the robustness of the meta-analysis results. RESULTS: A total of 10 studies involving 4,690 participants were identified. The summary relative risk comparing persons with the highest concentration categories of ferritin with the lowest concentration categories of ferritin was 1.87 (95% confidence interval 1.50-2.34; I2  = 20.1%). Linear dose-response showed that an increase in ferritin of 10 µg/L increased the risk of GDM by 8% (1.08, 95% confidence interval 1.05-1.13, I2  = 55.1%; n = 4). A non-linear dose-response relationship also showed a consistently increasing risk of GDM with increased ferritin. No evidence of publication bias was detected. CONCLUSIONS: The findings from this meta-analysis suggest that increased ferritin levels are associated with an increased risk of GDM; however, we require further prospective cohort studies to confirm the results, especially the dose-response relationship between ferritin and GDM.

[Clinical outcomes of trimetazidine in patients with acute ST segment elevation myocardial infarction without ST segment resolution after primary percutaneous coronary intervention].

OBJECTIVE: To evaluate prospectively the clinical outcomes of trimetazidine (TMZ) in patients with acute ST segment elevation myocardial infarction (STEMI) without ST segment resolution (STR) after primary percutaneous coronary intervention (PPCI). METHODS: From August 2005 to October 2007, 138 acute STEMI patients without STR after PPCI were randomly assigned to either with TMZ therapy (TMZ group, n = 70) or without TMZ (control group, n = 68). Baseline characteristics, PCI features and clinical outcomes during hospitalization were compared between the two groups. Left ventricular ejection fraction (LVEF) and major adverse cardiac events (MACE, including death, re-infarction and target vessel revascularization) at Days 30 and 180 after discharge were also compared. RESULTS: The baseline clinical characteristics were comparable between the two groups. There was no significant difference in MACE rates at Days 30 and 180 between the two groups (10/70 vs 11/68, P > 0.05; 15/70 vs 13/68, P > 0.05, respectively). The LVEFs of TMZ group at Days 30 and 180 were significantly superior to the control group (51 +/- 8)% vs (45 +/- 7)%, P < 0.05; (56 +/- 7)% vs (49 +/- 8)%, P < 0.05, respectively). CONCLUSION: Use of TMZ for patients with acute STEMI without STR after primary PCI can improve the left ventricular function at Days 30 and 180.

[Multifocal papillary thyroid carcinoma: clinical analysis of 168 cases].

OBJECTIVE: To investigate the clinical features and treatment of multifocal papillary thyroid carcinoma (PTC). METHODS: A retrospective survey was carried out in 648 patients with PTC who underwent surgery from January 1997 to December 2006. One hundred and sixty-eight cases of the patients presented with multiple tumor masses (> or = 2). The risk factors, including sex of the patients, age at diagnosis, family history of thyroid tumor, multiplicity and bilaterality of tumor, extra-thyroidal extension, lymph node involvement and other were analyzed between solitary PTC and multifocal PTC group. RESULTS: The mean age of the patients was 42 years (range, 14 - 78 years), included 49 male and 119 female. Tumor foci were found in both thyroid lobes in 117 cases (69.6%). Patients with multifocal PTC were characterized by a higher ratio of male (P = 0.004), family history of thyroid tumor (P = 0.031), neck lymph node metastasis (P = 0.008) and extra-thyroidal extension (P = 0.001). However, solitary PTC tended to be with a higher rate of benign goiters in pathologic examination. In multifocal PTC group, male, neck lymphadenectasis, > or = 3 tumor masses or bilaterality of tumor tended to presented with larger tumor, more neck lymph node metastasis and extra-thyroidal extension; And a less malignant tumor in the cases detected with benign goiters in histological examination. By the end of 2007, 164 cases (97.6%) completed follow-up with a mean period of 46.1 months (range, 2 - 127 months), 5 died in the meantime. One patient has been followed-up for 16 months for suspect of lung metastases by chest X-ray. Recurrence occurred in 8 patients and were re-resected, 2 in remnant thyroid and 6 in neck lymph nodes. The overall 1-, 2-, 5-, and 10-year survival rate was 98.2%, 97.4%, 96.5% and 96.5%, respectively. American Joint Committee on Cancer (AJCC) stage was associated with prognosis significantly (chi(2) = 168.832, P = 0.000). CONCLUSIONS: Multifocus is one of the clinical features of PTC and is more malignant than solitary PTC. Total thyroidectomy with central compartment neck dissection could be standard treatment. Lateral nodal dissection is not necessary except for the cases with lymph node metastasis. AJCC stage is still the best prognostic factor.

[Effect of tirofiban in acute anterior myocardial infarction patients without ST segment resolution after primary percutaneous coronary intervention].

OBJECTIVE: To observe the effect of glycoprotein receptor blockade tirofiban in acute anterior myocardial infarction patients without ST segment resolution after primary percutaneous coronary intervention (PCI). METHODS: From April 2006 to April 2008, 157 acute anterior myocardial infarction patients without ST segment resolution after PCI were randomly allocated to tirofiban (intravenous bolus 10 microg/kg followed by intravenous infusion of 0.15 microgxkg(-1)xmin(-1) for 48 h, n = 80) or equal volume saline (control group, n = 77). Baseline characteristics, PCI features and clinical outcomes during hospitalization, left ventricular ejection fractions (LVEF) and major adverse cardiac events (MACE, including death, re-infarction and target vessel revascularization) at 30 and 180 days after discharge were compared between the two groups. RESULTS: The baseline clinical characteristics were comparable between the two groups. Compared to control group, the MACE rates and re-infarction rates at 30 days (6.3% vs.18.2%, P < 0.05; 1.3% vs.9.1%, P < 0.05, respectively) and 180 days (10.0% vs.23.4%, P < 0.05; 2.5% vs.10.4%, P < 0.05, respectively) were significantly reduced in tirofiban group. LVEF value was significantly higher in tirofiban group at 30 days and 180 days compared with those in control group [(51 +/- 6)% vs. (46 +/- 8)%, P < 0.05; (57 +/- 7)% vs. (50 +/- 9)%, P < 0.05]. Hemorrhagic complications were similar between the two groups. CONCLUSION: Use of tirofiban for acute anterior myocardial infarction patients without ST segment resolution after PCI is safe and can significantly improve 30 and 180 days clinical outcomes after discharge.

Effect of Moderate and Vigorous Aerobic Exercise on Incident Diabetes in Adults With Obesity: A 10-Year Follow-up of a Randomized Clinical Trial.

This randomized clinical trial assesses the long-term effect of vigorous and moderate exercise on incident diabetes over a 10-year follow-up after a 12-month exercise intervention.

[Expression and clinical significance of CD44v6 and sCD44v6 in gastric carcinoma].

OBJECTIVE: To evaluate the correlation of CD44v6 and sCD44v6 expression with the biological activity of gastric carcinoma. METHODS: Mucosa samples from 103 gastric carcinoma patients and 10 healthy persons (control) were examined using immunohistochemical SP method; sCD44v6 level in peripheral blood samples was detected with ELISA in 86 gastric cancer patients, 30 gastric ulcer patients and 30 healthy controls. The follow-up period was 3-91 months for 88 patients in CD44v6 group and 1-91 months for 55 patients in sCD44v6 group. RESULTS: (1) Positive expression of CD44v6 was found in 60.2% of gastric carcinoma, where as 0% in the normal gastric mucosa. CD44v6 protein expression was positively correlated with TNM stage, perigastric lymph node metastasis, presence of cancerous embolic angiopathy and Borrmann classification (P <0.05), but was not correlated with invasion depth, differentiation, metastasis and survival (P > 0.05); 77.8% of the patient with liver metastasis had a strong CD44v6 protein expression. (2) sCD44v6 level in the peripheral blood of gastric carcinoma patient was significantly higher than that in gastric ulcer patient or healthy control; Compared with palliative gastrectomy, sCD44v6 level significantly went down after radical operation. No relationship between sCD44v6 level and the pathological features was found, which included invasion depth, perigastric lymph node metastasis, presence of cancerous embolic angiopathy, differentiation and Borrmann classification; The survival in the high sCD44v6 level group was longer than that in low sCD44v6 level group ( P = 0.0281), but no significant difference was observed by Cox Regression analysis (P = 0.415). (3) No apparent correlation was observed between CD44v6 expression in gastric cancer and sCD44v6 concentration in peripheral blood (P>0.05). CONCLUSION: Detection of CD44v6 expression in the gastric cancer may be helpful in evaluating the biological features and the survival in gastric carcinoma. The level of sCD44v6 in the blood may be also helpful in differential diagnosis, evaluation of surgical treatment and biological activity for gastric cancer. No apparent correlation is observed between CD44v6 expression in the cancer and that of sCD44v6 in the blood.

Apoptosis induced by preoperative oral 5'-DFUR administration in gastric adenocarcinoma and its mechanism of action.

AIM: To study the apoptosis induced by preoperative oral 5'-DFUR administration in gastric adenocarcinoma and its mechanism of action. METHODS: Sixty gastric cancer patients were divided randomly into three groups (20 each group) before operation: group one:5'-DFUR oral administration at the dose of 800-1200 mg/d for 3 - 5 d, group two: 500 mg 5-FU + 200 mg/d CF by venous drip for 3 - 5 d,group three (control group). One or two days after chemotherapy, the patients were operated. Fas/FasL,PD-ECGF and PCNA were examined by immunohistochemistry and apoptotic tumor cells were detected by in situ TUNEL method. Fifty-four patients received gastrectomy, including 12 palliative resections and 42 radical resections. Six patients were excluded. Finally 18 cases in 5'-DFUR group, 16 cases in CF+5-FU group, and 20 cases in control group were analyzed. RESULTS: There was no significant difference in patient mean age, gender, white blood cell count, haematoglobin (HB),thromboplastin, perioperative complication incidence, radical or palliation resection, invasion depth (T), lymphonode involvement (N),metastasis (M) and TNM staging among the three groups. However,the PCNA index (PI) in 5'-DFUR group (40.51+/-12.62) and 5-FU+CF group (41.12+/-15.26) was significantly lower than that in control group (58.33+/-15.69) (F=9.083, P=0.000). The apoptotic index (AI) in 5'-DFUR group (14.39+/-9.49) and 5-FU+CF group (14.11+/-9.68)was significantly higher than that in control group (6.88+/-7.37) (F=4.409, P=0.017).The expression rates of Fas and FasL in group one and group three were 66.7% (12/18) and 50% (9/18), 43.8% (7/16) and 81.3% (13/16), 45.0% (9/20) and 85% (17/20), respectively. The expression rate of FasL in 5'-DFUR group was significantly lower than that in the other two groups (chi2=6.708, P=0.035). Meanwhile, the expression rate of PD-ECGF was significantly lower in 5'-DFUR group (4/18,28.6%) than in CF+5-FU group(9/16,56.3%)and control group (13/20,65.0%) (chi2=7.542, P=0.023). The frequency of Fas expression was significantly correlated with palliative or radical resection (chi2=7.651, P=0.006), invasion depth (chi2=8.927, P=0.003), lymphatic spread (chi2=4.488, P=0.034) and UICC stages (chi2=8.063, P=0.045) respectively. By the end of March 2005,45 patients were followed up. The 0.5-, 1-, 2-, 3-year survival rates were 96%,73%,60%,48%, respectively, which were related with T, N, M and Fas expression, but not with PD-ECGF and FasL expression. CONCLUSION: Preoperative oral 5'-DFUR administration may induce apoptosis of gastric carcinoma cells and decrease tumor cell proliferation index,but cannot improve the prognosis of patients with gastric cancer.Down-regulation of FasL and PD-ECGF expression mediated by 5'-DFUR may be one of its anti-cancer mechanisms.Fas expression correlates with the progression of gastric carcinoma and may be an effective prognostic factor.

[Study on the prognostic value of hepatocyte growth factor and c-met for patients with hepatocellular carcinoma].

OBJECTIVE: To analyze the prognostic value of hepatocyte growth factor (HGF) and c-met for patients with hepatocellular carcinoma (HCC) after hepatectomy. METHODS: Twenty-five patients undergoing partial hepatectomy for HCC were studied. Serum HGF level was determined using ELISA kit before and after operation respectively. c-met protein and mRNA expression in cancerous and paracancerous tissues were detected by immunohistochemical and RT-PCR methods respectively. The correlations of clinical-pathologic parameters with the HGF level in serum and c-met expression in cancerous tissue were analyzed respectively. RESULTS: HCC patients had a significantly higher concentration of serum HGF than normal controls and chronic hepatitis B respectively [(1.03 +/- 0.09) ng/ml vs (0.69 +/- 0.02) ng/ml and (0.74 +/- 0.09) ng/ml]. No significant difference in serum HGF was observed between HCC and cirrhosis patients with Child-Pugh score B/C [(1.03 +/- 0.09) ng/ml vs (1.04 +/- 0.11) ng/ml]. Serum HGF concentrations were positively correlated with tumor size (> 5 cm), node cirrhosis, portal vein tumor thrombi (PVTT) and preoperative alpha-fetoprotein (AFP) level (> or = 400 microg/L). After the resection of tumor, serum HGF concentration had a peak on the third postoperative day (POD), and then declined, but did not return to normal level on the tenth POD. From preoperative day to third POD, HGF concentration had a higher elevation in patients with major resection than with local resection. Moderately or strongly positive expression of c-met protein was observed in 21 cancerous regions (21/25), and only in 5 paracancerous regions. The intensive expression of c-met mRNA was 100% (25/25) detectable in the cancerous tissues, but only 24% (6/25) in the paracancerous tissues. The expression extent of c-met protein was correlated with portal vein tumor thrombi (PVTT). In paracancerous tissues, the expression of c-met protein was more intense in patients with cirrhosis than those without cirrhosis. The patients with recurrence or metastases after operation had a higher level of serum HGF and more intensive expression of c-met than other patients. No significant association was observed between HGF in serum and c-met expression in cancerous tissue. CONCLUSIONS: The over-expression of HGF and its receptor c-met indicate an adverse prognosis for HCC patients. The sustained high level of serum HGF after hepatectomy may be a factor related to early tumor recurrence and metastasis.

Vitamin B6 Prevents Endothelial Dysfunction, Insulin Resistance, and Hepatic Lipid Accumulation in Apoe (-/-) Mice Fed with High-Fat Diet.

Backgrounds. VitB6 deficiency has been associated with a number of adverse health effects. However, the effects of VitB6 in metabolic syndrome are poorly understood. Methods. VitB6 (50 mg/kg/day) was given to Apoe (-/-) mice with hkdigh-fat diet (HFD) for 8 weeks. Endothelial dysfunction, insulin resistance, and hepatic lipid contents were determined. Results. VitB6 administration remarkably increased acetylcholine-induced endothelium-dependent relaxation and decreased random blood glucose level in Apoe (-/-) mice fed with HFD. In addition, VitB6 improved the tolerance of glucose and insulin, normalized the histopathology of liver, and reduced hepatic lipid accumulation but did not affect the liver functions. Clinical and biochemical analysis indicated that the levels of VitB6 were decreased in patients with fatty liver. Conclusions. Vitamin B6 prevents endothelial dysfunction, insulin resistance, and hepatic lipid accumulation in Apoe (-/-) mice fed with HFD. Supplementation of VitB6 should be considered to prevent metabolic syndrome.

Activation of activator protein 2 alpha by aspirin alleviates atherosclerotic plaque growth and instability in vivo.

AIMS: Aspirin has been used for the secondary prevention and treatment of cardiovascular disease for several decades. We investigated the roles of transcriptional factor activator protein 2α (AP-2α) in the beneficial effects of aspirin in the growth and vulnerability of atherosclerotic plaque. METHODS AND RESULTS: In mice deficient of apolipoprotein E (Apoe-/-), aspirin (20, 50 mg/kg/day) suppressed the progression of atherosclerosis in aortic roots and increased the plaque stability in carotid atherosclerotic plaques induced by collar-placement. In vivo lentivirus-mediated RNA interference of AP-2α reversed the inhibitory effects of aspirin on atherosclerosis in Apoe-/- mice. Mechanically, aspirin increased AP-2α phosphorylation and its activity, upregulated IkBα mRNA and protein levels, and reduced oxidative stress in cultured vascular smooth muscle cells. Furthermore, deficiency of AP-2α completely abolished aspirin-induced upregulation of IkBα levels and inhibition of oxidative stress in Apoe-/- mice. Clinically, conventional doses of aspirin increased AP-2α phosphorylation and IkBα protein expression in humans subjects. CONCLUSION: Aspirin activates AP-2α to upregulate IkBα gene expression, resulting in attenuations of plaque development and instability in atherosclerosis.

Effects of Moderate and Vigorous Exercise on Nonalcoholic Fatty Liver Disease: A Randomized Clinical Trial.

IMPORTANCE: Nonalcoholic fatty liver disease (NAFLD) is a prevalent risk factor for chronic liver disease and cardiovascular disease. OBJECTIVE: To compare the effects of moderate and vigorous exercise on intrahepatic triglyceride content and metabolic risk factors among patients with NAFLD. DESIGN, SETTING, AND PARTICIPANTS: In this randomized clinical trial, participants with central obesity and NAFLD were recruited from community-based screening in Xiamen, China, from December 1, 2011, through December 25, 2013. Data analysis was performed from August 28, 2015, through December 15, 2015. INTERVENTIONS: Participants were randomly assigned to vigorous-moderate exercise (jogging 150 minutes per week at 65%-80% of maximum heart rate for 6 months and brisk walking 150 minutes per week at 45%-55% of maximum heart rate for another 6 months), moderate exercise (brisk walking 150 minutes per week for 12 months), or no exercise. MAIN OUTCOMES AND MEASURES: Primary outcome, change in intrahepatic triglyceride content measured by proton magnetic resonance spectroscopy at 6 and 12 months; secondary outcomes, changes in body weight, waist circumference, body fat, and metabolic risk factors. RESULTS: A total of 220 individuals (mean [SD] age, 53.9 [7.1] years; 149 woman [67.7%]) were randomly assigned to control (n = 74), moderate exercise (n = 73), and vigorous-moderate exercise (n = 73) groups. Of them, 211 (95.9%) completed the 6-month follow-up visit; 208 (94.5%) completed the 12-month follow-up visit. Intrahepatic triglyceride content was reduced by 5.0% (95% CI, -7.2% to 2.8%; P < .001) in the vigorous-moderate exercise group and 4.2% (95% CI, -6.3% to -2.0%; P < .001) in the moderate exercise group compared with the control group at the 6-month assessment. It was reduced by 3.9% (95% CI, -6.0% to -1.7%; P < .001) in the vigorous-moderate exercise group and 3.5% (95% CI, -5.6% to -1.3%; P = .002) in the moderate exercise group compared with the control group at the 12-month assessment. Changes in intrahepatic triglyceride content were not significantly different between vigorous-moderate and moderate exercise at the 6- or 12-month assessment. Body weight, waist circumference, and blood pressure were significantly reduced in the vigorous-moderate exercise group compared with the moderate exercise and control groups at the 6-month assessment and in the vigorous-moderate and moderate exercise groups compared with the control group at the 12-month assessment. In addition, body fat was significantly reduced in the vigorous-moderate exercise group compared with the moderate exercise and control groups at the 12-month assessment. After adjusting for weight loss, the net changes in intrahepatic triglyceride content were diminished and became nonsignificant between the exercise and control groups (except for the moderate exercise group at the 6-month assessment). CONCLUSIONS AND RELEVANCE: Vigorous and moderate exercise were equally effective in reducing intrahepatic triglyceride content; the effect appeared to be largely mediated by weight loss. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01418027.