Effects of Rapamycin and Rapamycin-loaded Poly(lactic-co-glycolic)Acid Nanoparticles on Apoptosis and Expression of bcl-2 and p27(kip1) Proteins of Human Umbilical Arterial Vascular Smooth Muscle Cell / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investgate the effects of rapamycin(RPM)and RPM-loaded poly(lactic-co-glycolic)acid(PLGA)nanoparticles(NPs)on the apoptosis of human umbilical arterial vascular smooth muscle cells(HUASMCs)in vitro and expression of bcl-2 and p27(kip1) protein.</p><p><b>METHODS</b>HUASMCs were cultured in vitro and divided to RPM and RPM-PLGA-NPs groups treated at 3 different concentration by 12 and 24 hours,with M231-smooth muscle growth supplements medium and null-PLGA-NPs treated groups as controlled. The apoptosis of HUASMCs was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining and flow cytometry. The expressions of bcl-2 and p27(kip1) were detected by streptacidin/peroxidase immunohistochemical method. The effect on cellular proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromidecolorimetry.</p><p><b>RESULTS</b>The proliferation of HUASMCs was inhibited by RPM and RPM-PLGA-NPs in a dose-dependent manner. DNA electrophoresis showed DNA ladder in RPM and RPM-PLGA-NPs groups and classical scalar strips in control groups. The apoptotic indexes of RPM 100 ng/ml group and RPM-PLGA-NPs 500 ng/ml group detected by flow cytometry were(45.45<2.36)% and(35.04<5.64)%,respectively,which were significantly higher than that of M231-smooth muscle growth supplements control group [(2.60<0.95)%,all P<0.01]. The apoptotic indexes of groups incubated with RPM and RPM-PLGA-NPs for 24 hours were significantly higher than those of groups which incubated for 12 hours(P<0.05,P<0.01). The positive expression indexes(PEI)of p27(kip1) and bcl-2 protein were higher in RPM and RPM-PLGA-NPs groups than that of control groups. The Spearman's rank correlation coefficient test showed that there was no significant correlation between the PEI of p27(kip1) and the apoptotic indexes in the RPM group and RPM-PLGA-NPs group(P>0.05).</p><p><b>CONCLUSIONS</b>Rapamycin-loaded PLGA nanoparticles and rapamycin have similar effects in inhibiting proliferation and inducing apoptosis;meanwhile,they upregulate the expression of p27(kip1) protein without downregulating the expression of bcl-2 protein in HUASMCs in vitro. RPM-PLGA-NPs has more potent pro-apoptotic effect than equivalent dose of RPM but is not linearly correlated with the p27(kip1) expression level.</p>

A multi-center, double-blind, randomized, parallel group study to evaluate the effects of two different doses of losartan on morbidity and mortality in Chinese patients with symptomatic heart failure intolerant of angiotensin converting enzyme inhibitor treatment / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There have been no mortality/morbidity endpoint studies with losartan in Chinese heart failure patients. The objective was to evaluate the effects of high-dose vs. low-dose losartan on clinical outcomes in Chinese subjects with heart failure.</p><p><b>METHODS</b>This study was a post hoc analysis of the Heart failure Endpoint evaluation of Angiotensin II Antagonist losartan (HEAAL) trial (n = 545). Chinese adults with symptomatic heart failure (New York Heart Association (NYHA) II-IV) intolerant of treatment with angiotensin converting enzyme (ACE) inhibitors were randomized to losartan 150 mg or 50 mg daily. The primary endpoint was the composite event rate of all-cause death or hospitalization for heart failure. Safety and tolerability were assessed.</p><p><b>RESULTS</b>Median follow-up was 4.8 years. Baseline characteristics were generally similar to the overall HEAAL cohort. Overall, 120 (44.1%) subjects in the losartan 150 mg group and 137 (50.2%) subjects in the losartan 50 mg group died (any cause) or were hospitalized for heart failure (hazard ratio (OR) 0.807, 95%CI 0.631 - 1.031). There were no notable differences between treatment groups in the proportion of subjects with adverse experiences.</p><p><b>CONCLUSION</b>The results of this post hoc analysis in Chinese subjects, although not powered to show significance, were generally consistent with the main study results, which demonstrated a significantly reduced risk of all cause death or hospitalization for heart failure with daily losartan 150 mg vs. losartan 50 mg in subjects with symptomatic heart failure and intolerance to ACE inhibitors, supporting the use of the higher dose for optimum clinical benefit.</p>

Coronary angiography with dual source computed tomography: initial experience / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To explore the scan technique and image quality of coronary angiography with dual source computed tomography (CT) without oral metoprolol preparation.</p><p><b>METHODS</b>Plain and enhanced dual source CT coronary angiography without oral metoprolol preparation was prospectively performed in 600 patients. Calcium scoring with plain scan images as well as multi-planar reconstruction (MPR), maximum intensity projection (MIP), and volume rendering technique (VRT) reconstruction with enhanced scan images were performed in all cases. The scan technique and post-reconstruction experience was summarized. The image quality was classified as 1 to 4 points, and coronary segments classified according to the American Heart Association standards were evaluated.</p><p><b>RESULTS</b>The average calcium score of the 600 cases was 213.6 +/- 298.7 (0-3,216.5). The average heart rate of the enhanced scan was 82.1 +/- 16.2 (47-139) bpm. The post-reconstruction methods with which coronary segments could be shown as best as possible consisted of single phase reconstruction method, two or more phases supplemented method, and electrocardiogram editing method. Altogether 8,457 coronary segments were evaluated, among which 97.2% were evaluated as point 1, 1.7% point 2, 0.5% point 3, and 0.6% point 4. The coronary segments in 261 cases were completely normal, while 360 segments were diagnosed with < 50% stenosis and 625 segments with > or = 50% stenosis.</p><p><b>CONCLUSIONS</b>Excellent coronary artery image can be obtained with dual source CT in patients with any heart rate without oral metoprolol preparation. Heart rate is not a major source of the artifact, coronary segments can be well shown with single or multiple-phase reconstruction method.</p>