[ANXA8 Regulates Proliferation of Human Non-Small Lung Cancer Cells A549 via EGFR-AKT-mTOR Signaling Pathway].

Annexin A8 (ANXA8) is a member of the annexin family, which had been reported to regulate multiple cancer cellular processes including proliferation, metastasis and inflammation. However, the specific role of ANXA8 in lung cancer cell biology remains unknown. Our previous transcriptome study revealed that ANXA8 mRNA was downregulated in curcumin analog (MHMD) -treated human non-small lung cancer cells (A549 cell line). Here, we continued to study the ANXA8 expression in A549 cells using reverse transcription-quantitative PCR and Western blotting, compared with that in human normal bronchial epithelium cells (BE-AS-2B cell line). Overexpression of ANXA8 via transfection of pEGFP-ANXA8 recombinant vector contributed to the proliferation and migration of A549 cells. Moreover, the cell cycle protein cyclin E1 was upregulated in ANXA8-transfected A549 cells. Knockdown of ANXA8 using an RNA interference technique decreased A549 cell viability and restrained their migration in vitro. The expression levels of multiple cellular factors, including EGFR, PI3K, Akt, mTOR, p70S6K and 4EBP1, in the epidermal growth factor receptor (EGFR) signaling pathway were also altered by ANXA8 knockdown or overexpression in A549 cells, which confirmed the activation of the EGFR/Akt/mTOR signaling pathway by ANXA8. The present results provided evidence to support further investigation of the functional identification of ANXA8 in lung cancer cells in the future.

MiR-1908 improves cardiac fibrosis after myocardial infarction by targeting TGF-ß1.

OBJECTIVE: To investigate the role and mechanism of micro ribonucleic acid (miR)-1908 in myocardial fibrosis after myocardial infarction. MATERIALS AND METHODS: In in-vivo experiments, the rat model of myocardial infarction was established, and miR-1908 was up-regulated by lentivirus with miR-1908 overexpression. Cardiac function of rats was detected by echocardiography. Transforming growth factor-ß1 (TGF-ß1) and Smad2/3 expressions in infarction border zone were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Masson staining was used to detect the fibrosis, thus studying the role of miR-1908 in the myocardial fibrosis model. In in-vitro experiments, myocardial fibroblasts were isolated and cultured. Oxygen glucose deprivation (OGD) model was established to mimicking the ischemic condition; the relationship between miR-1908 and TGF-ß1 was verified using luciferase reporter vector, lentivirus and small-interfering RNA (siRNA) in TGF-ß1. RESULTS: In-vivo experiments showed that the miR-1908 expression was down-regulated at 4 weeks after myocardial infarction. The up-regulation of miR-1908 significantly improved the cardiac function, reduced the myocardial fibrosis, and inhibited the expressions of TGF-ß1 and Smad2/3. In-vitro experiments revealed that TGF-ß1 was a target gene of miR-1908 and miR-1908 could inhibit the Smad2/3 expression through TGF-ß1. CONCLUSIONS: MiR-1908 can improve the myocardial fibrosis through the target gene TGF-ß1.

[Predictors of clinically significant bleeding events in bivalirudin-treated Chinese patients with acute myocardial infarction undergoing percutaneous coronary intervention].

Objective: This study was designed to further clarify the independent predictors of clinically significant bleeding events in bivalirudin-treated patients with acute myocardial infarction(AMI) undergoing percutaneous coronary intervention (PCI). Methods: A total of 3 023 AMI patients from 88 centers of China who underwent PCI and received periprocedural bivalirudin treatment between August 2012 and December 2015 were involved in this study.The primary outcome was clinically significant bleeding events defined as the Bleeding Academic Research Consortium(BARC) grades 2-5, with 30 days after PCI.A multivariate Logistic regression model was performed to identify the independent predictors of the primary outcome. Results: Bleeding events occurred in 88(2.9%) patients during the 30-day follow up, with clinically significant bleeding (BARC types 2-5) in 22(0.7%) and BARC types 3-5 in 7(0.2%). Multivariate regression analysis revealed radial access (OR: 0.196, 95%CI: 0.074-0.517, P=0.001) as the independent protector of the significant bleeding events, anemia (OR: 2.956, 95%CI: 1.024-8.528, P=0.045) and eGFR<30 ml/min (OR: 7.860, 95%CI: 1.515- 40.776, P=0.014) as independent risk factors. Conclusions: The rate of clinically significant bleeding complications in Chinese AMI patients undergoing PCI with concomitant use of bivalirudin is low in real-world clinical practice.Radial access is independent protective factor that reduces bleeding events, whereas anemia and eGFR <30 ml/min are independent risk factors that increase bleeding risk.

Association between ß1 adrenergic receptor gene Arg389Gly polymorphism and risk of heart failure: a meta-analysis.

Numerous studies have evaluated the association between Arg389Gly polymorphism in the ß1 adrenergic receptor gene and heart failure risk. However, the specific association is still controversial. We performed a meta-analysis of all case-control studies that evaluated the association between Arg389Gly polymorphism and heart failure in humans. Studies were identified in the PubMed, Embase, and China National Knowledge Infrastructure databases. Two reviewers independently assessed the studies. Six case-control studies with a total of 1736 participants were included in the meta-analysis, including 882 cases with heart failure and 854 controls, and our results showed no association between the Arg389Gly polymorphism and heart failure [ArgArg vs GlyGly: odds ratio (OR) = 0.84, 95% confidence interval (CI) 0.59-1.20; ArgArg vs ArgGly: OR = 0.95, 95%CI 0.78-1.16; dominant model: OR = 1.08, 95%CI 0.89-1.31; recessive model: OR = 0.96, 95%CI 0.69-1.35]. No publication bias was found in the present study (all P values > 0.05). In conclusion, the ß1 adrenergic receptor gene Arg389Gly polymorphism might not be associated with heart failure risk. Further large and well-designed studies are needed to confirm this conclusion.

Meta-analysis of angiotensin-converting enzyme insertion/deletion polymorphism and myocardial infarction in Han Chinese.

It has been suggested that the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism is linked to susceptibility to myocardial infarction (MI). In this study, we performed a meta-analysis to assess the relationship between ACE I/D polymorphism and MI in the Chinese Han population. Eight studies including a total of 1609 subjects were selected for inclusion in the analysis. The references were retrieved using the PubMed and China National Knowledge Infrastructure databases. The analyses were performed using the STATA 12.0 software. ORs and 95%CI were assessed after the collected data were pooled for analysis. There was a significant association between ACE I/D polymorphism and MI in the Chinese Han population (II vs DD: OR = 0.40, 95%CI = 0.31-0.53; II vs DI: OR = 0.72, 95%CI = 0.57-0.91; the dominant model: OR = 1.74, 95%CI = 1.41-2.16; the recessive model: OR = 0.47, 95%CI = 0.38-0.60). The sensitivity analysis further confirmed the result. Publication bias was not observed in this meta-analysis. The ACE I/D polymorphism may be a risk factor for MI in the Chinese Han population. However, larger studies with a stratified case-control population and biological characterization are needed to validate this finding.

The prevalence of Parkinson's disease continues to rise after 80 years of age: a cross-sectional study of Chinese veterans.

OBJECTIVE: The purpose of this study was to examine whether the prevalence of Parkinson's disease (PD) continues to rise after 80 years of age. METHODS: This is a two-stage, multi-center, cross-sectional study using a stratified cluster sampling approach was employed. Subjects included veterans at ≥ 60 years of age living in veterans' communities for at least one month in 18 major cities across China. In the first step, possible PD was screened using a PD screening scale. Demographic and relevant information were collected. In the second step, PD diagnosis was established using the United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) diagnostic criteria. RESULTS: The study was conducted during the period from December 2009 to December 2012. The study included 277 veterans' communities. Among the approached 11,593 subjects, 9676 subjects, (9096 men, 580 women) responded. The response rate was 83.46%.The age was ≥ 80 years in 6722 (69.47%) subjects. A diagnosis of PD was established in 228 subjects (2.36%) in the entire sample. The rate of PD was 2.65% in those with an age of ≥ 80 years. The rate of PD increased with increasing age (0%, 1.84%, 2.60% and 3.68% in the subjects at < 70, 70-79, 80-89 and ≥ 90 years of age, respectively; χ2 = 10.891, p = 0.001 in chi-square test). The rate of PD was higher in men (2.44%) than in women (1.46%) on the surface. However, no significant difference was detected (p = 0.241). CONCLUSIONS: The prevalence of PD continues to increase beyond the age of 80 years. The prevalence of PD in Chinese veterans is not lower than that in other countries and regions.

OX40 ligand levels and high-sensitivity C-reactive protein levels in blood from local coronary plaque and the femoral artery in patients with acute coronary syndrome or stable angina.

OX40 ligand (OX40L) and high-sensitivity C-reactive protein (hs-CRP) play important roles in the pathogenesis of atherosclerosis. In this study, consecutive patients with acute coronary syndrome (ACS; n = 90) or stable angina (SA; n = 40) and healthy control subjects (n = 50) were evaluated to assess plasma OX40L and serum hs-CRP levels in local coronary plaque and the femoral artery. OX40L and hs-CRP levels in the femoral artery were significantly higher in patients with ACS compared with controls. OX40L and hsCRP levels in local coronary plaque (OX40L(c) and hs-CRP(c), respectively) were significantly higher in ACS than in SA patients. OX40L and hs-CRP levels were positively correlated with each other and were also correlated with fibrinogen levels. The number of complex lesions was correlated with OX40L(c) and hs-CRP(c) levels. It is concluded that the OX40L(c) level was highly sensitive for evaluating the inflammatory response in ACS and elevated levels of OX40L(c) may be a valuable predictive marker for increased risk of atherosclerotic progression in ACS patients.

Niemann-Pick type C1 protein influences the delivery of cholesterol to the SREBP: SCAP complex

The proposed role of Niemann-Pick type C1 protein (NPC1) in the delivery of low-density lipoprotein (LDL) cholesterol to the sterol regulatory element binding protein (SREBP):SREBP cleavage activation protein (SCAP) complex in the endoplasmic reticulum has been largely based on indirect studies and remains contentious. The major aim of the present study was to assess whether NPC1 is involved in the delivery of LDL cholesterol to the SREBP:SCAP complex. A cell line stably expressing green fluorescence protein-SCAP was cultured in the presence of U18666A, which can induce a Niemann-Pick type C disease phenotype, in order to locate the SREBP:SCAP complex by fluorescence microscopy. Our major finding was that defective NPC1 caused a delay in the ability of LDL cholesterol to suppress SREBP processing. This was shown in a time-course experiment by the effect of LDL on green fluorescence protein-SCAP movement when cells were treated with pharmacological agents to induce a Niemann-Pick type C disease phenotype. We demonstrated directly by fluorescence microscopy that defective NPC1 causes a delay in LDL cholesterol delivery to the endoplasmic reticulum where SCAP senses cholesterol.

Niemann-Pick type C1 protein influences the delivery of cholesterol to the SREBP:SCAP complex.

The proposed role of Niemann-Pick type C1 protein (NPC1) in the delivery of low-density lipoprotein (LDL) cholesterol to the sterol regulatory element binding protein (SREBP):SREBP cleavage activation protein (SCAP) complex in the endoplasmic reticulum has been largely based on indirect studies and remains contentious. The major aim of the present study was to assess whether NPC1 is involved in the delivery of LDL cholesterol to the SREBP:SCAP complex. A cell line stably expressing green fluorescence protein-SCAP was cultured in the presence of U18666A, which can induce a Niemann-Pick type C disease phenotype, in order to locate the SREBP:SCAP complex by fluorescence microscopy. Our major finding was that defective NPC1 caused a delay in the ability of LDL cholesterol to suppress SREBP processing. This was shown in a time-course experiment by the effect of LDL on green fluorescence protein-SCAP movement when cells were treated with pharmacological agents to induce a Niemann-Pick type C disease phenotype. We demonstrated directly by fluorescence microscopy that defective NPC1 causes a delay in LDL cholesterol delivery to the endoplasmic reticulum where SCAP senses cholesterol.

[The clinical value of continuous perfusion percutaneous transluminal coronary angioplasty in treatment of coronary artery disease].

Fourty two patients with coronary artery disease were studied. Among them 22 were treated with continuous perfusion percutaneous transluminal coronary angioplasty (CPPTCA) and 20 with percutaneous transluminal coronary angioplasty (PTCA). It was found that patients treated with CPPTCA can stand longer time of dilatation during operation than those treated with PTCA (P < 0.01). Moreover, angina pectoris and ischemic changes of ECG occurred later during CPPTCA than during PTCA (P < 0.001). The incidences of ventricular tachycardia, ventricular fibrillation, residual trans-stenosis pressure gradient and residual stenosis were all lower in patients treated with CPPTCA than those with PTCA (P < 0.01-0.001). However, there was no significant difference in the incidence of reinfarction and one-year mortality between the patients after CPPTCA and PTCA.

Angiographic prediction of cardiac events after first acute transmural myocardial infarction. A prospective study of 108 patients.

108 patients with acute myocardial infarction (MI), aged 70 years or younger, underwent left ventriculography and coronary arteriography (mean one month) after infarction and were followed up for an average period of 22 months (range 5-47 months). The contribution of angiographic variables to a first cardiac event (death, recurrent infarction, coronary artery bypass grafting or congestive heart failure) was evaluated with Kaplan-Meier survival curve analysis and long-rank test. Patients with cardiac events had left ventricular dilation, systolic dysfunction, multivessel coronary disease and lack of residual flow to the infarct region. Multivariate analysis showed that left ventricular end-systolic volume (P less than 0.001), end-diastolic volume (P less than 0.01) and the number of the diseased coronary vessels (P less than 0.05) were of significance in predicting the outcome. This prospective study indicates that in survivors of first acute transmural MI, cardiac catheterization performed one month after infarction can provide additive prognostic information that can be used to stratify risk.

Spontaneous alterations in left ventricular regional wall motion after acute myocardial infarction.

For assessing the relationship between the left ventricular (LV) wall motion abnormalities and the status of residual flow to the infarcted region, the extent of coronary artery disease and one-year outcome, 60 patients with a first transmural, Q-wave myocardial infarction (MI) underwent serial echocardiographic examinations. The abnormal wall motion (AWM) score was calculated, and the cardiac events (death, reinfarction, severe ventricular arrhythmia or congestive heart failure) after discharge were recorded. The AWM score of the infarcted area was higher in patients with total occlusion than in those with subtotal occlusion (anterior MI: 14.6 +/- 2.4 vs 7.2 +/- 2.1; inferior MI: 9.7 +/- 2.1 vs 5.1 +/-1.2, all P less than 0.01). Regional wall motion of the noninfarcted area was preserved in patients with single vessel disease but decreased in those with multivessel disease. In patients who developed cardiac events in follow-up period a higher AWM (16.4 +/- 3.7) was found than in those who did not (8.9 +/- 3.1, P less than 0.05). A score of greater than 13 had a strong prediction of cardiac events after acute MI, with a sensitivity of 81%, specificity of 94% and positive predictive accuracy of 88%.

Beneficial effect of residual flow to the infarct region on left ventricular volume changes after acute myocardial infarction.

To determine the relationship between alterations in left ventricular (LV) volumes and residual flow to the infarct region after myocardial infarction (MI), 57 patients with a first acute transmural MI underwent two-dimensional echocardiography within 48 hours of infarction and after 1 month. A reduction in ST segment elevation by greater than or equal to 35% of the peak value of ST segment elevation within the initial 6 hours was used as an indirect indicator for early reperfusion of the infarct-related artery (IRA). IRA patency and collateral circulation were assessed by coronary arteriography performed at 1 month. LV volumes increased in patients with a persistent ST segment elevation within the initial 6 hours of infarction and in those with a totally occluded IRA without collaterals. However, LV volumes were unchanged in patients with early reperfusion and in those who had subtotally occluded IRA or who had collateral circulation. LV dilation (greater than or equal to 20% increase in end-diastolic volume) occurred less often when early reperfusion and angiographically patent IRA or collateral supply to the infarct zone were present. This prospective study indicates that residual flow to the infarct region may exert a beneficial effect on LV volume changes after acute MI.

[A correlative study of ECG and coronary arteriogram findings after acute myocardial infarction].

To evaluate the electrocardiographic value in the prediction of reperfusion state of the infarct-related artery (IRA), serial changes in ST segment elevation were assessed in 38 patients with acute myocardial infarction (AMI). ST segment elevation decreased by 35% or more within 8 hours of peak sigma ST in 16 of the 20 patients with subtotal occlusion, but in none of the patients with total occlusion of the IRA (P less than 0.01). Myocardial infarct size estimated by peak serum CK-MB, sigma Q and QRS score was smaller and left ventricular function was better in patients with rapid resolution of ST segment elevation than in those with persistent ST elevation. The study indicates that a fall of ST segment elevation by 35% or more of the peak sigma ST within 8 hours of infarction may be a useful indicator of early reperfusion of the IRA in patients with AMI.

Value of angina pectoris after myocardial infarction in predicting extent of coronary artery disease.

Clinical, hemodynamic, and angiographic data were examined in 53 patients who underwent catheterization within 6 months of documented acute transmural myocardial infarction (MI). The patients were divided into two groups on the basis of presence (23 patients, group I) or absence (30 patients, group II) of angina pectoris 1 month after MI. Group I patients had more severe coronary artery disease and a greater prevalence of multivessel disease than group II patients. Partial preservation of segmental left ventricular wall function in group I was related to the presence of collateral vessels. In patients with single vessel disease, incidence of spontaneous recanalization of the infarct-related artery was more common in group I as compared with those in group II. It is concluded that angina pectoris after MI suggests multivessel disease or infarct-related artery recanalization. Coronary angiography may be advised in these patients in order to select adequate therapeutic interventions and improve prognosis.