Converging evidence implicates the dopamine D3 receptor gene in vulnerability to schizophrenia

The dopamine D3 receptor has been implicated in the pathophysiology of schizophrenia (SZ). A glycine‐to‐serine polymorphism at codon 9 of the dopamine D3 receptor gene (DRD3), rs6280, has been widely studied for its association with SZ, but with conflicting results. Altered levels of DRD3 mRNA have also been reported in SZ compared with normal controls. Moreover, it has been suggested that DRD3 is subject to recent positive selection in European populations. To explore the potential role of DRD3 in SZ from these various aspects, we conducted a threefold study. First, we tested the genetic association of rs6280 with SZ in 685 SZ patients and 768 normal controls. Second, we examined DRD3 mRNA levels in peripheral leukocytes in a subset of 37 patients and 37 controls. Finally, we investigated the possible recent positive selection on DRD3 in an East Asian population. Consequently, we observed that the genotypic distribution of rs6280 was nominally associated with SZ (P = 0.045), with the ancestral CC genotype being significantly over‐represented in SZ patients. DRD3 mRNA levels were significantly lower in patients than in controls (P = 5.91E?5). The derived C‐allele of rs6280 might have been subject to recent positive selection (P < 0.001) in the East Asian population. Taken together, our results suggest that DRD3, a gene possibly under natural selection, might be involved in vulnerability to SZ in the Han Chinese population. These findings may further add to the body of data implicating DRD3 as a schizophrenia risk gene. © 2011 Wiley‐Liss, Inc.     

聚甲基丙烯酸甲酯颗粒对人滑膜细胞核因子κB受体激动剂配体/骨保护蛋白表达的影响

背景：多种因子可以影响骨保护蛋白/核因子κB受体激动剂配体/核因子κB受体激动剂（Osteoprotegerin/receptor activator of nuclear factor-kappaB/ligand of receptor-activator of nuclear factor-kappaB,OPG/RANKL/RANK）系统的表达影响骨代谢,那么松动假体周围的骨水泥颗粒是否也通过影响其代谢参与假体松动过程？目的：观察聚甲基丙烯酸甲酯颗粒对人滑膜细胞RANKL/OPG表达的影响。方法：体外培养人滑膜细胞,在滑膜细胞培养体系中分别加入质量浓度为0（空白对照）,0.2,1,10g/L的聚甲基丙烯酸甲酯骨水泥颗粒,采用荧光定量PCR检测上述各浓度PMMA颗粒作用不同时间后滑膜细胞内RANKL、OPG的表达量及其比值。结果与结论：与空白对照组相比,各实验组滑膜细胞内RANKL、OPG的表达量均有下降;随着与聚甲基丙烯酸甲酯颗粒共培养时间延长,各实验组滑膜细胞内RANKL、OPG表达均有下降趋势,而RANKL/OPG表达比值无明显变化。说明聚甲基丙烯酸甲酯颗粒在对滑膜细胞产生生物学反应时并不干扰假体周围骨代谢的动态平衡,并未直接参与人工关节假体的无菌性松动。     

聚甲基丙烯酸甲酯颗粒对人滑膜细胞核因子κB受体激动剂配体/骨保护蛋白表达的影响

背景:多种因子可以影响骨保护蛋白/核因子κB受体激动剂配体/核因子κB受体激动剂(Osteoprotegerin/receptor activator of nuclear factor-kappaB/ligand of receptor-activator of nuclear factor-kappaB,OPG/RANKL/RANK)系统的表达影响骨代谢,那么松动假体周围的骨水泥颗粒是否也通过影响其代谢参与假体松动过程?目的:观察聚甲基丙烯酸甲酯颗粒对人滑膜细胞RANKL/OPG表达的影响。方法:体外培养人滑膜细胞,在滑膜细胞培养体系中分别加入质量浓度为0(空白对照),0.2,1,10g/L的聚甲基丙烯酸甲酯骨水泥颗粒,采用荧光定量PCR检测上述各浓度PMMA颗粒作用不同时间后滑膜细胞内RANKL、OPG的表达量及其比值。结果与结论:与空白对照组相比,各实验组滑膜细胞内RANKL、OPG的表达量均有下降;随着与聚甲基丙烯酸甲酯颗粒共培养时间延长,各实验组滑膜细胞内RANKL、OPG表达均有下降趋势,而RANKL/OPG表达比值无明显变化。说明聚甲基丙烯酸甲酯颗粒在对滑膜细胞产生生物学反应时并不干扰假体周围骨代谢的动态平衡,并未直接参与人工关节假体的无菌性松动。     

聚甲基丙烯酸甲酯颗粒对人滑膜细胞核因子κB受体激动剂配体/骨保护蛋白表达的影响

背景：多种因子可以影响骨保护蛋白/核因子κB受体激动剂配体/核因子κB受体激动剂(Osteoprotegerin / receptor activator of nuclear factor-kappaB/ligand of receptor-activator of nuclear factor-kappaB,OPG/RANKL/RANK)系统的表达影响骨代谢,那么松动假体周围的骨水泥颗粒是否也通过影响其代谢参与假体松动过程？ 目的：观察聚甲基丙烯酸甲酯颗粒对人滑膜细胞RANKL/OPG表达的影响。 方法：体外培养人滑膜细胞,在滑膜细胞培养体系中分别加入质量浓度为0(空白对照),0.2,1,10 g/L的聚甲基丙烯酸甲酯骨水泥颗粒,采用荧光定量PCR检测上述各浓度PMMA颗粒作用不同时间后滑膜细胞内RANKL、OPG的表达量及其比值。 结果与结论：与空白对照组相比,各实验组滑膜细胞内RANKL、OPG的表达量均有下降;随着与聚甲基丙烯酸甲酯颗粒共培养时间延长,各实验组滑膜细胞内RANKL、OPG表达均有下降趋势,而RANKL/OPG表达比值无明显变化。说明聚甲基丙烯酸甲酯颗粒在对滑膜细胞产生生物学反应时并不干扰假体周围骨代谢的动态平衡,并未直接参与人工关节假体的无菌性松动。     

Diagnostic Performance of Machine Learning Based CT-FFR in Detecting Ischemia in Myocardial Bridging and Concomitant Proximal Atherosclerotic Disease

BackgroundThe diagnostic performance of coronary computed tomography angiography-derived fractional flow reserve (CT-FFR) in detecting ischemia in myocardial bridging (MB) has not been investigated to date.MethodsThis retrospective multicentre study included 104 patients with left anterior descending MBs. MB was classified as either superficial or deep, short, or long, whereas all MB vessels were further divided into <50%, 50% to 69%, and ≥70% groups, according to proximal lumen stenosis on invasive coronary angiography. Diagnostic performance and receiver operating characteristics (ROC) of CT-FFR to detect lesion-specific ischemia was assessed on a per-vessel level, using invasive FFR as reference standard. Intraclass correlation coefficient (ICC) and Bland-Altman plots were used for agreement measurement.ResultsForty-eight MB vessels (46.2%) showed ischemia by invasive FFR (≤0.80). Sensitivity, specificity, and accuracy of CT-FFR to detect functional ischemia were 0.96 (0.85 to 0.99), 0.84 (0.71 to 0.92), and 0.89 (0.81 to 0.94), respectively, in all MB vessels. There were no differences in diagnostic performance between superficial and deep MB or between short and long MB (all P > 0.05). The accuracy of CT-FFR was 0.96 (0.85 to 0.99) in ≥70% stenosis, 0.82 (0.67 to 0.91) in 50% to 69% stenosis, and 0.89 (0.51 to 0.99) in <50% stenosis (P = 0.081). Bland-Altman analysis showed a slight mean difference between CT-FFR and invasive FFR of 0.014 (95% limit of agreement, –0.117 to 0.145). The ICC was 0.775 (95% confidence interval, 0.685-0.842, P < 0.001).ConclusionsCT-FFR demonstrated high diagnostic performance for identifying functional ischemia in vessels with MB and concomitant proximal atherosclerotic disease when compared with invasive FFR. However, the clinical use of CT-FFR in patients with MB needs further study for stronger and more robust results.     

Lack of correlation between CSF glutamate levels and PSQI scores in heavy smokers

Sleep and Breathing - Glutamate is an excitatory neurotransmitter in the central nervous system that participates in initiation and maintenance of sleep and wakefulness. The mechanisms involved...     

Efficacy and safety of sacubitril/valsartan compared with olmesartan in Asian patients with essential hypertension: A randomized,double‐blind, 8‐week study

This study assessed the efficacy and safety of angiotensin receptor neprilysin inhibitor sacubitril/valsartan vs olmesartan in Asian patients with mild‐to‐moderate hypertension. Patients (N = 1438; mean age, 57.7 years) with mild‐to‐moderate hypertension were randomized to receive once daily administration of sacubitril/valsartan 200 mg (n = 479), sacubitril/valsartan 400 mg (n = 473), or olmesartan 20 mg (n = 486) for 8 weeks. The primary endpoint was reduction in mean sitting systolic blood pressure (msSBP) from baseline with sacubitril/valsartan 200 mg vs olmesartan 20 mg at Week 8. Secondary endpoints included msSBP reduction with sacubitril/valsartan 400 mg, and reductions in clinic and ambulatory BP and pulse pressure (PP) vs olmesartan. In addition, changes in msBP from baseline in the Chinese subpopulation, elderly (≥65 years), and in patients with isolated systolic hypertension (ISH) were assessed. Sacubitril/valsartan 200 mg provided a significantly greater reduction in msSBP than olmesartan 20 mg at Week 8 (between‐treatment difference: −2.33 mm Hg [95% confidence interval (CI) −4.00 to −0.66 mm Hg], P < 0.05 for non‐inferiority and superiority). Greater reductions in msSBP were also observed with sacubitril/valsartan 400 mg vs olmesartan 20 mg (−3.52 [−5.19 to −1.84 mm Hg], P < 0.001 for superiority). Similarly, greater reductions in msBP were observed in the Chinese subpopulation, in elderly patients, and those with ISH. In addition, both doses of sacubitril/valsartan provided significantly greater reductions from baseline in nighttime mean ambulatory BP vs olmesartan. Treatment with sacubitril/valsartan 200 or 400 mg once daily is effective and provided superior BP reduction than olmesartan 20 mg in Asian patients with mild‐to‐moderate hypertension and is generally safe and well tolerated.     

A prospective multicenter parallel-controlled trial of TIVOLI biodegradable-polymer-based sirolimus-eluting stent compared to ENDEAVOR zotarolimus-eluting stent for the treatment of coronary artery disease: 8-month angiographic and 2-year clinical follow-up results

Background  Available drug-eluting stents (DES) have achieved great success in reducing restenosis rates. Recently, investigators have demonstrated that the durable polymer carrier plays a significant role in DES-related hypersensitive reaction and delays vessel healing. TIVOLI stent is a novel sirolimus-eluting coronary stent with biodegradable coating containing sirolimus and polylactic-co-glycolic acid (PLGA) polymer. The present study sought to evaluate the effectiveness and safety of the TIVOLI biodegradable-polymer-based sirolimus-eluting stent in treating patients with coronary artery disease. 

Methods  A prospective, multicenter clinical trial comparing TIVOLI biodegradable coated sirolimus-eluting stent with ENDEAVOR zotarolimus-eluting stent was conducted in 324 patients (TIVOLI group: 168 patients; ENDEAVOR group: 156 patients) at 12 centers in China to demonstrate the non-inferiority of in-stent late loss with TIVOLI stent compared to ENDEAVOR stent in subjects with a maximum of two de novo native coronary artery lesions (lesion length ≤40 mm, reference vessel diameter 2.25–4.00 mm). The primary end point was angiographic in-stent late loss at 8-month. The secondary end points were clinical outcomes at 2 years, including major adverse cardiac events (cardiac death, myocardial infarction, or target-lesion revascularization) and stent thrombosis.

Results  Angiographic late lumen loss at 8 months in the TIVOLI group was superior to the ENDEAVOR group (in-stent (0.25±0.33) mm vs. (0.57±0.55) mm, diff (95% CI) –0.23 (–0.32, –0.14), P <0.0001; in-segment (0.25±0.33) mm vs. (0.42±0.55) mm, diff (95% CI) –0.13 (–0.23, –0.02), P=0.0083). The rate of in-stent binary restenosis at 8 months was reduced from 8.6% in the ENDEAVOR group to 2.9% in the TIVOLI group (P=0.0229). Compared to ENDEAVOR stent, TIVOLI stent resulted in a significant reduction in target-lesion revascularization (4.2% vs. 9.6%, P=0.0495) at 2 years. The two-year major adverse cardiac events (MACE) rate was lower for the TIVOLI group, but not significantly different (6.6% vs. 10.9%, P=0.1630).

Conclusions  TIVOLI was superior to ENDEAVOR stent with respect to late lumen loss at 8 months, and it yielded both lower rates of angiographic binary restenosis at 8 months and target lesion revascularization (TLR) at 2 years. The MACE rate at 2 years was comparable in both groups.

     

胃网膜右动脉在非体外循环冠状动脉旁路移植术中的临床应用

目的 探讨胃网膜右动脉(RGEA)在非体外循环冠状动脉旁路移植术(OPCAB)中的临床应用.方法 2008年12月至2009年7月南京医科大学第一附属医院对38例冠心病患者采用RGEA行OPCAB治疗,根据在OPCAB中采用的移植血管不同将76例患者分为两组,RGEA组:38例,男36例,女2例;年龄65.87±6.2...