Association between genetic variants of the ADD1 and GNB3 genes and blood pressure response to the cold pressor test in a Chinese Han population: the GenSalt Study

Genetic factors influence blood pressure (BP) response to the cold pressor test (CPT), which is a phenotype related to hypertension risk. We examined the association between variants of the α-adducin (ADD1) and guanine nucleotide binding protein (G protein) β-polypeptide 3 (GNB3) genes and BP response to the CPT. A total of 1998 Han Chinese participants from the Genetic Epidemiology Network of Salt Sensitivity completed the CPT. The area under the curve (AUC) above the baseline BP during the CPT was used to measure the BP response. Twelve single-nucleotide polymorphisms (SNPs) of the ADD1 and GNB3 genes were selected and genotyped. Both single-marker and haplotype association analyses were conducted using linear mixed models. The rs17833172 and rs3775067 SNPs of the ADD1 gene and the rs4963516 SNP of the GNB3 gene were significantly associated with the BP response to CPT, even after adjusting for multiple testing. For the ADD1 gene, the AA genotype of SNP rs17833172 was associated with lower systolic BP (SBP) reactivity (P<0.0001) and faster BP recovery (P=0.0003). The TT genotype of rs3775067 was associated with slower SBP recovery (P=0.004). For the GNB3 gene, the C allele of SNP rs4963516 was associated with faster diastolic BP recovery (P=0.002) and smaller overall AUC (P=0.003). Haplotype analysis indicated that the CCGC haplotype of ADD1 constructed by rs1263359, rs3775067, rs4961 and rs4963 was significantly associated with the BP response to CPT. These data suggest that genetic variants of the ADD1 and GNB3 genes may have important roles in BP response to the CPT. Future studies aimed at replicating these novel findings are warranted.     

Anti-inflammation and antioxidant effect of Cordymin, a peptide purified from the medicinal mushroom Cordyceps sinensis, in middle cerebral artery occlusion-induced focal cerebral ischemia in rats

Cordymin is a peptide purified from the medicinal mushroom Cordyceps sinensis. The present study investigated the effects of Cordymin in prevention of focal cerebral ischemic/reperfusion (IR) injury. The right middle cerebral artery occlusion model was used in the study. The effects of Cordymin on mortality rate, neurobehavior, grip strength, glutathione content, lipid Peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na⁺K⁺ATPase activity glutathione S transferase activity and on the regulation of C3 and C4 protein level, polymorphonuclear cells, interleukin-1β and tumor necrosis factor-α in a rat model were studied respectively. Treatment (orally) of Cordymin significantly boosted the defense mechanism against cerebral ischemia by increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may have helped the brain recover from ischemic injury. Moreover, Cordymin significantly inhibited infiltration of polymorphonuclear cells and IR-induced up-regulation of the brain production of C3 protein level, interleukin-1β and tumor necrosis factor-α. Cordymin significantly improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. Our findings suggest that cordymin have a neuroprotective effect in the ischemic brain, which is due to the inhibition of inflammation and increase of antioxidants activity related to lesion pathogenesis. Cordymin can be used as potential preventive agent against cerebral ischemia-reperfusion injury.     

收缩性心力衰竭兔神经激素的变化研究

目的 探讨兔收缩性心力衰竭(systolic heart failure,SHF)的血浆神经激素脑钠肽(BNP)、去甲肾上腺素(NE)、肾上腺素(EPI)、血管紧张素Ⅱ(AngⅡ)的变化.方法 将40只新西兰大白兔随机分为两组:SHF组(行腹主动脉缩窄联合主动脉瓣毁损术)、假手术组(行假手术),通过超声心动图和血流动力学检查心功能的改变,第12周抽血检查血浆BNP、NE、EPI、AngⅡ水平.结果 与假手术组相比,SHF组左室腔明显增大,收缩功能显著下降,血浆BNP、NE、EPI、AngⅡ水平较假手术组明显升高(P＜0.01).结论 SHF组的神经激素水平明显增高.     

左心室瘢痕负荷SPECT相位分析法检测及其对心脏再同步治疗疗效的影响

目的 观察慢性心力衰竭患者心脏再同步治疗(CRT)后有反应和无反应者之间左心室瘢痕负荷的差异性,评价左心室瘢痕负荷对CRT疗效的影响.方法 对30例2006年至2010年因慢性心力衰竭在南京医科大学第一附属医院接受CRT的患者进行静息核素心肌显像检查,应用相位分析技术检测左心室瘢痕负荷、收缩期相位时间标准差( phase S D)和带宽(BW)并用来评价心脏同步性.以术后6个月超声心动图的检测结果及随访6个月内是否因心力衰竭住院作为分组标准,左心室射血分数(LVEF)提高≥0.05且无因心力衰竭住院的患者入选反应组,LVEF提高＜0.05或者入院1次以上的患者入选无反应组,观察两组之间左心室瘢痕负荷和同步性指标之间的差异.结果 30例患者中反应组19例(男8例),无反应组11例(男8例).两组之间术前临床资料相似,年龄、性别均差异无统计学意义;有反应组术前QRS时限显著大于无反应组[(163.0±7.7)ms对(134.6±11.8) ms,P＜0.05];两组术前LVEF差异无统计学意义,但术后有反应组显著高于无反应组(0.49±0.02对0.33±0.15,P＜0.01).两组患者左心室瘢痕负荷和CRT术后左心室同步性差异具有统计学意义,有反应组患者的左心室瘢痕负荷明显低于无反应组(24.6％±3.6％对36.5％±3.9％,P=0.022);有反应组左心室同步性较好,收缩期相位时间标准差明显小于无反应组(28.1°±4.4°对56.1°±6.9°,P＜0.01),收缩期带宽明显小于无反应组(88.0°±13.9°对170.1°±24.4°,P＜0.01).左心室瘢痕负荷和心脏同步性对CRT疗效具有明显的影响.结论 接受CRT的慢性心力衰竭患者,左心室瘢痕负荷和CRT术后心脏同步性与CRT疗效密切相关.     

放化疗结合中医药治疗食管癌的临床研究进展

食管癌的非手术治疗手段目前有放疗、化疗、中医药治疗.放疗及化疗都有其局限性和不足之处:放疗过程中不可避免会出现放射性食管炎、放射性肺炎等不良反应;化疗的不良反应,尤其是消化系反应、骨髓抑制、肝肾功能损害等,使部分肿瘤患者生活质量降低,甚至造成化疗疗程中断,影响治疗效果.中医药能明显减轻放化疗治疗的不良反应、提高患者生存质量、延长生存期.本文就近年来放化疗结合中医药治疗食管癌的临床研究作一综述.     

幽门螺杆菌检测方法在动物模型中的评估

幽门螺杆菌(Helicobacter pylori,H.pylori)是慢性胃炎及消化性溃疡的主要致病因素,并与胃癌及胃黏膜相关性淋巴组织淋巴瘤(mucosa-associated lymphoid tissue,MALT)的发生密切相关.随着H.pylori动物模型更广泛、合理的利用,为临床、基础研究提供了非常有价值的帮助.目前,国内相关动物模型中检测H.pylori的报道较少,大多数实验研究中H.pylori的检测需要处死动物获取检测标本以确定接种是否成功,而非侵入性的检测方法仍不成熟.本文综述了目前研究报道的动物模型中七种侵入性及非侵入性H.pylori检测方法,且可根据不同实验条件和要求选择传统的和新颖的检测方法,以便我们更加方便、准确的检测动物模型中感染的H.pylori.     

Retinoic Acid-related Orphan Receptor-α Is Induced in the Setting of DNA Damage and Promotes Pulmonary Emphysema

Rationale: The discovery that retinoic acid-related orphan receptor (Rora)-α is highly expressed in lungs of patients with COPD led us to hypothesize that Rora may contribute to the pathogenesis of emphysema. Objectives: To determine the role of Rora in smoke-induced emphysema. Methods: Cigarette smoke extract in vitro and elastase or cigarette smoke exposure in vivo were used to model smoke-related cell stress and airspace enlargement. Lung tissue from patients undergoing lung transplantation was examined for markers of DNA damage and Rora expression. Measurements and Main Results: Rora expression was induced by cigarette smoke in mice and in cell culture. Gene expression profiling of Rora-null mice exposed to cigarette smoke demonstrated enrichment for genes involved in DNA repair. Rora expression increased and Rora translocated to the nucleus after DNA damage. Inhibition of ataxia telangiectasia mutated decreased the induction of Rora. Gene silencing of Rora attenuated apoptotic cell death in response to cigarette smoke extract, whereas overexpression of Rora enhanced apoptosis. Rora-deficient mice were protected from elastase and cigarette smoke induced airspace enlargement. Finally, lungs of patients with COPD showed evidence of increased DNA damage even in the absence of active smoking. Conclusions: Taken together, these findings suggest that DNA damage may contribute to the pathogenesis of emphysema, and that Rora has a previously unrecognized role in cellular responses to genotoxicity. These findings provide a potential link between emphysema and features of premature ageing, including enhanced susceptibility to lung cancer.