Effect of valsartan on the expression of angiotensin II receptors in the lung of chronic antigen exposure rats

Background Many studies have suggested that angiotensin Ⅱ （Ang Ⅱ） and its receptors may be involved in the development of asthma. However, the expression of angiotensin Ⅱ receptors （AGTR） is not clear in the lung tissue of chronic asthmatics. This study was designed to determine the relationship between airway remodeling, dysfunction and the expression of AGTRs in a rat model of asthma. Methods Rats were sensitized with ovalbumin （OVA） for 2 weeks. Sixty minutes before an inhalation challenge, the rats were pretreated either with valsartan （15, 30, 50 mg.kg-1.d-1） or saline intragastrically. Then the rats received an OVA challenge for 30 alternative days. Acetylcholine （Ach）-induced bronchoconstriction was measured after the final antigen challenge. White cell counts in bronchoalveolar lavage fluid （BALF） and morphological changes in the airways were then assessed. The levels of transforming growth factor-beta 1 （TGF-β1） and platelet-derived growth factor （PDGF） in BALF were detected by ELISA. The levels of AGTR1 and AGTR2 mRNA and protein in lung tissues were measured by RT-PCR and Western blotting. Results AGTR1 mRNA and protein levels in repeatedly OVA-challenged rats were significantly increased as compared with negative controls. The AGTR1 mRNA expression versus white cell counts of BALF and airway wall thickness （mainly in small airways） in lungs of chronic antigen-exposed rats were positively correlated. Valsartan decreased the level of AGTR1 in repeatedly OVA-challenged rats. However, AGTR2 mRNA and protein levels in the OVA-challenged rats and high-dose valsartan-treated rats （50 mg.kg-1.d-1） were also increased. Valsartan significantly decreased inflammatory cell accumulation and attenuated Ach-evoked bronchoconstriction in repeatedly antigen-challenged rats. Valsartan also decreased allergen-induced structural changes in rat airway （including total airway wall thickness and smooth muscle area） and the levels of TGF-β1 and PDGF in BALE Conclusions AGTR     

Cigarette smoking and the risk of endometrial cancer:A meta-analysis

OBJECTIVE:Epidemiologic findings are inconsistent concerning the association of endometrial cancer risk with cigarette smoking.We conducted a meta-analysis of epidemiologic studies to examine this relation.METHODS:A systematic literature search up to June of 2007 was performed in MEDLINE and EMBASE.Study-specific risk estimates were pooled using a random-effects model.RESULTS:Ten prospective and 24 case-control studies were included in the analysis of the effect of ever smoking.Ever smoking was statistically significantly associated with a reduced risk of endometrial cancer among prospective studies(relative risk 0.81;95% confidence interval[CI],0.74-0.88) and case-control studies(odds ratio 0.72;95% CI,0.66-0.79).The inverse association was significant among current and former smokers.Six prospective and 6 case-control studies were included in the quantitative analysis.We noted that an increase in smoking of 20 cigarettes per day was statistically significantly associated with 16% and 27% reduced risks of endometrial cancer in prospective and case-control studies,respectively.We also found that cigarette smoking was significantly associated with a decreased risk of endometrial cancer among postmenopausal women(relative risk 0.71;95% CI,0.65-0.78) but not among premenopausal women.In addition,the risk reduction seemed to be stronger among hormone replacement therapy users than nonusers.CONCLUSION:Cigarette smoking was found to be significantly associated with a reduced risk of endometrial cancer,especially among postmenopausal women.(C) 2008 Elsevier Inc.All rights reserved.     

黄芩苷对HT-29细胞炎症模型PI3K/NF-κB信号通路的影响及机制探讨

目的:观察黄芩苷对人结肠癌上皮细胞株HT~(-2)9的炎症模型中磷脂酰肌醇3激酶(PI3K)/丝氨酸苏氨酸蛋白激酶(Akt)/核转录因子-κB(NF-κB)信号通路的影响,并探讨其机制。方法:以肿瘤坏死因子(TNF)-α及脂多糖(LPS)共同诱导HT~(-2)9细胞,建立细胞炎症模型。实验分为6组,空白组加入完全培养基孵育,实验过程中不予任何药物干预,模型组给予h TNF(20μg·L~(~(-1)))黄芩苷孵育12 h后,再给LPS(1 mg·L~(~(-1)))孵育15 h;柳氮磺胺吡啶组在模型组的基础上,加入柳氮磺胺吡啶(SASP,500μmol·L~(~(-1)));黄芩苷组在模型组基础上给予不同剂量(1,10,100μg·L~(~(-1)))黄芩苷孵育24 h。噻唑蓝(MTT)法检测黄芩苷(1,10,100μg·L~(~(-1)))对细胞生长的影响;免疫印迹(Western blot)法检测黄芩苷(1,10,100μg·L~(~(-1)))对PI3K,Akt,NF-κB等蛋白表达,酶联免疫吸附(ELISA)法检测黄芩苷(1,10,100μg·L~(~(-1)))对细胞上清中TNF-α,白细胞介素(IL)-6等含量的影响。结果:与模型组比较,黄芩苷组、柳氮磺胺吡啶组的细胞上清液中TNF-α,IL-6,IL-8,IL~(~(-1))分泌量明显减少(P0.05),且两药联合应用对TNF-α,IL-6,IL-8,IL~(~(-1))分泌量的减弱效应更强(P0.01)。与模型组比较,黄芩苷组(1,10,100μg·L~(~(-1))),柳氮磺胺吡啶组(500μmol·L~(~(-1)))中的PI3K蛋白磷酸化水平,Akt磷酸化水平,NF-κB活化入核水平,环氧化酶~(-2)(Cox~(-2))蛋白,β-连环蛋白(β-catenin)蛋白,天冬氨酸蛋白水解酶-9(Caspase-9)蛋白,人凋亡相关因子配体(Fas L)蛋白表达均明显减少(P0.05)。结论:黄芩苷能减轻HT~(-2)9细胞炎症反应,抑制PI3K磷酸化,下调Akt的活化,抑制NF-κB的活化入核,从而抑制TNF-α,IL-6等炎症因子的分泌,发挥其抗炎效应,提示黄芩苷可能通过以抑制Akt的活化,抑制NF-κB的核转位,发挥其抗炎作用。     

Requirements for transfusion and postoperative outcomes in orthotopic liver transplantation：A meta-analysis on aprotinin

AIM：To study the effect of aprotinin used in orthotopic liver transplantation （OLT） on the intraoperative requirement for blood products and on the incidence of laparotomy for bleeding, thrombotic events and mortality.
METHODS： A systematic review of the literature in the electronic database Medline and the Clinic Trials Registry Database was performed. Literature that did not fit our study were excluded. Patients in the reviewed studies were divided into two groups; one group used aprotinin （aprotinin group） while the other did not （control group）. The data in the literature that fit our requirements were recorded. Weighted mean differences （WMD） in the requirements for blood products between the aprotinin group and the control group were tested using a fixed effect model. A Z test was performed to examine their reliability; the Fleiss method of fixed effect model was used to analyze data on postoperative events, and odds ratios （ORs） were tested and merged.
RESULTS： Seven citations were examined in our study. Among them, a requirement for blood products was reported in 4 studies including 321 patients, while postoperative events were reported in 5 studies including 477 patients. The requirement for red blood cells and fresh frozen plasma in the aprotinin group was statistically lower than that in the control group （WMD=-1.80 units, 95% CI,-3.38 to-0.22; WMD=-3.99 units, 95% CI,-6.47 to-1.50, respectively）. However, no significant difference was indicated in the incidence of laparotomy for bleeding, thrombotic events and mortality between the two groups. Analysis on blood loss, anaphylactic reactions and renal function was not performed in this study due to a lack of sufficient information.
CONCLUSION： Aprotinin can reduce the intraoperative requirement for blood products in OLT, and has no significant effect on the incidence of laparotomy for bleeding, thrombotic events and mortality.     

药物经济学在中医“治未病”中的应用

目的:探讨药物经济学在中医"治未病"中的应用。方法:通过对药物经济学及中医"治未病"理论的简单介绍,并以活血化瘀药预防脑梗死为例,分析以药物经济学方法研究中医"治未病"的可行性及必要性。结果与结论:应用药物经济学方法评价中医"治未病",将建立更加客观的中药评价体系,更好地指导临床合理用药。     

青少年癫癎患者的心理分析及护理对策

目的探讨青少年癫痫患者的心理问题并作出相应的护理干预对策。方法通过对56例住院青少年癫痫患者进行讲解、咨询释疑、发放宣传资料等方式,对其心理问题回顾性分析,加以归纳总结。结果青少年癫痫患者都不同程度存在心理问题,通过开展护理干预措施,提高青少年患者的生活质量,促进疾病康复。结论有效的护理干预措施能有效地降低青少年癫痫患者的心理问题发生。     

自拟补肾活血温经通络汤治疗膝骨性关节炎临床观察

目的：观察评价自拟补肾活血温经通络汤治疗膝骨性关节炎的临床疗效．并与筋骨痛消丸作比较。方法：将283例患者随机分为治疗组152例,治疗组给予补肾活血温经通络汤治疗。对照组131例,给予筋骨痛消丸治疗,疗程均为3个月,观测对膝关节疼痛,活动范围及可行走距离等。结果：治疗组有效率及优良率优于对照组。结论：补肾活血温经通络汤可以有效治疗膝骨性关节炎,显示了中医整体观辨证论治理念的优势。     

脂氧素A4调控转化生长因子-β1干预小鼠支气管肺发育不良的机制研究

探讨脂氧素A4(lipoxin A4,LXA4)对新生小鼠高氧诱导所致的支气管发育不良(bronchopulmonary dysplasia,BPD)的保护作用及可能机制?方法:利用高氧损伤诱导BPD动物模型,将新生C57BL/6J小鼠随机分成:空气对照组?模型组?LXA4干预组?转化生长因子-β1(transforming growth factor-β1,TGF-β1)中和抗体(1D11)干预组,记录仔鼠体重和生存情况,HE染色观察出生后肺组织病理改变,qPCR法检测肺纤维化指标及转化生长因子-βⅠ型受体(transforming growth factor-β receptor 1,TGF-βR1)和转化生长因子-βⅡ型受体(transforming growth factor-β receptor 2,TGF-βR2)的表达水平?结果:①模型组新生小鼠较空气对照组体重减低且活力差?②肺组织大体标本观察:与空气对照组相比,各组小鼠肺体积减小,色泽暗淡?与空气对照组(d13)相比,LXA4干预组和1D11干预组小鼠肺外观与之相仿?③HE染色:除空气对照组外,各组肺组织均产生类似BPD的病理损伤?较模型组(d13)相比,LXA4干预组与1D11干预组的肺泡结构趋于正常化?④qPCR:与空气对照组相比,各组肺纤维化指标:纤维连接蛋白?平滑肌肌动蛋白-α?弹性蛋白?肌腱蛋白C?组织金属蛋白抑制剂-1及TGF-βR1?TGF-βR2的表达量均增加(P < 0.05)?与空气对照组相比,各组基质金属蛋白酶1相对表达量减少(P < 0.05);其中与模型组相比,LXA4干预组和1D11干预组基质金属蛋白酶1表达量上调(P < 0.05),且LXA4干预组上调更为显著(P < 0.05)?与空气组对照比较,模型组?LXA4干预组和1D11干预组Ⅰ型胶原表达量增高(P < 0.05);其中与模型组相比,LXA4干预组和1D11干预组Ⅰ型胶原表达减少(P < 0.05)?结论:LXA4可能是通过抑制TGF-β1信号通路下调肺纤维化相关因子,实现对高氧诱导BPD的保护作用?