丹参对视网膜静脉阻塞患者脂质过氧化物及超氧化物歧化酶的影响

目的：探讨丹参对视网膜静脉阻塞（ＲＶＯ）患者血浆脂质过氧化物（ＬＰＯ）含量及红细胞超氧化物歧化酶（ＳＯＤ）活性的影响。方法：静脉滴注丹参注射液治疗３６例ＲＶＯ患者,测定治疗前后ＲＶＯ患者ＬＰＯ含量及ＳＯＤ活性,选取３０例健康人作为对照。结果：与健康人相比,ＲＶＯ患者血浆ＬＰＯ含量明显升高,红细胞ＳＯＤ活性明显下降（Ｐ＜０．００１）;ＲＶＯ患者使用丹参治疗后血浆ＬＰＯ含量较治疗前下降（Ｐ＜０．０５）,红细胞ＳＯＤ活性较治疗前明显升高（Ｐ＜０．０１）;ＲＶＯ患者使用丹参治疗后血浆ＬＰＯ含量及红细胞ＳＯＤ活性与健康人相比,均无明显变化（Ｐ＞０．０５）。结论：丹参作为一种外源性自由基清除剂,可有效地增加ＲＶＯ患者红细胞ＳＯＤ活性,降低ＬＰＯ含量,对ＲＶＯ的防治有重要意义     

银杏达莫注射液治疗早期糖尿病肾病疗效的Meta分析

目的系统评价银杏达莫注射液治疗早期糖尿病肾病(DN)的疗效。方法计算机检索中国期刊全文数据库(CNKI)、维普中文科技期刊全文数据库和万方数字化期刊数据库,纳入银杏达莫注射液治疗早期DN的随机对照试验(RCT),进行方法学质量评价和疗效指标合并分析。结果经检索得到13个RCT,合计768例患者,所纳入试验方法质量学较低且样本含量较小,"漏斗图"呈不对称分布,提示可能存在发表偏倚及试验方法质量低下,发表偏倚提示阴性结果的试验可能未发表。结论 Meta分析结果显示,银杏达莫注射液试验组在降低早期糖尿病肾病患者24 h尿微量白蛋白排泄率、血尿素氮、甘油三酯、血液黏度、纤维蛋白原、MDA并提高SOD方面均尚需要设计严格、大样本的随机对照试验加以证实。     

Issues on the selection of non-inferiority margin in clinical trials

Objective The determination of non-inferiority margin is an important and confusing issue which directly influences the acceptability of a new medication. We reviewed the published literature, International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use （ICH） Guidelines and Committee for Proprietary Medicinal Products （CPMP） papers on the selection of non-inferiority margin and the corresponding statistical tests in clinical trials, in order to provide practical recommendations and suggestions for establishing reference criteria for the non-inferiority margin in China.
Data sources The literature on the selection of a non-inferiority margin and statistical tests was mainly extracted from relevant English articles on non-inferior clinical trials published from 1990 to 2007. The starting point （1990） was chosen due to lack of such papers published prior to 1990. This literature was searched via PubMed, Medline and Chinese Knowledge Information （CNKI）. ICH guidelines and CPMP papers were downloaded from their official websites. The keywords ＂clinical trial＂, ＂non-inferiority＂ and ＂non-inferiority margin＂ were used.
Study selection Forty-three original articles and critical reviews, ICH El0 guideline and CPMP papers were selected. Results The non-inferiority testing with treatment difference and ratio are commonly used, where the non-inferiority margin is determined with and without historical data. Traditionally, this margin is treated as a fixed value, while developed methods take the variation into account in the determination of this margin, on which the test depends is more convincing. The mixed margin consisting of a margin based on treatment difference and a margin based on treatment ratio can exactly control the type I error at the desirable level and obtain a better power. In this review, we also provide some recommendations and suggestions for the selection of the non-inferiority margin in the western countries and China.
Conclusions Besides the magnitude and variability of the standard control and placebo effects, the determination of the margin depends on other factors, such as, the safety profiles of the two comparative therapies, method of administration and product cost. Hence the margin should be made specifically for a certain case. Reference criteria for different medications should be given to avoid the arbitrary conclusion.     

延迟小剂量尿激酶治疗对脑梗死病人的血红细胞LPO、SOD的影响及临床疗效观察

目的:为了探讨延迟小剂量尿激酶治疗对脑梗死病人红细胞过氧化脂质(LPO)、超氧化歧化酶变化的影响和临床疗效。方法:对38例脑梗死病人静点尿激酶治疗,对治疗前后临床症状和红细胞LPO、SOD进行比较。结果:治疗后LPO明显降低,SOD明显增高,两者治疗前后比较有显著差异(P<0.01),临床疗效显著。结论:延迟小剂量尿激酶治疗对脑梗死后体内自由基增高,脂质过氧化反应及临床症状具有明显的改善作用。     

Postmarketing safety evaluation: depside salt injection made from Danshen (Radix Salviae Miltiorrhizae)

ObjectiveTo systematically examine the postmarketing safety of depside salt injection made from Danshen (Radix Salviae Miltiorrhizae), identify the potential risk factors, and ensure its clinical safety.MethodsWe examined a comprehensive series of studies on the production process, quality standards, pharmacology, population pharmacokinetics, and safety evaluation of depside salt injection made from Danshen (Radix Salviae Miltiorrhizae). Data from I-IV clinical drug trials, hospital information systems (HIS), and spontaneous reporting systems (SRS) were also analyzed.ResultsThe effective components of salvianolic acid salt content reached almost 100%, and the magnesium lithospermate B content reached more than 80%. The median lethal dose (LD50) calculated by the Bliss method was 1.49 g/kg, with 95% confidence intervals of 1.29–1.72 g/kg. Long-term tests on Beagle dogs indicated that doses of less than 80 mg/kg were safe and doses of 320 mg/kg were toxic. Adverse drug reactions (ADRs) included digestive disorders; drug-induced erythrocyte deformation in lung, liver, spleen, kidney, bone marrow, intestinal mucosa, lymph nodes, and other tissues; megakaryocytes in lung, liver, and spleen resulting from mild hemolysis; and mild hyperplasia in bone marrow hematopoietic tissue. Other studies indicated no irritative effect of the injection on local tissues and blood vessels, and no allergic reactions, erythrocyte coagulation, or hemolysis. SRS data showed that the most common ADRs were headache, head distention, dizziness, facial flushing, skin itching, thrombocytopenia, and the reversibility of elevated Aspartate transaminase. HIS data indicated no damage to renal function from using depside salt injection made from Danshen (Radix Salviae Miltiorrhizae) at a dosage higher than the recommended dose.ConclusionThis study analyzes the clinical characteristics of ADRs from depside salt injection made from Danshen (Radix Salviae Miltiorrhizae), and discusses the factors influencing such reactions. It provides scientific reference and recommendations for clinically safe medication of the Danshen injection.     

低抗凝活性肝素修饰超氧化物歧化酶的药代动力学研究

用高碘酸钠活化低抗凝活性肝素（ＬＡＡＨ）修饰猪血红细胞Ｃｕ，Ｚｎ－ＳＯＤ，制成ＬＡＡＨ（ＩＯ４）－ＳＯＤ。给兔１次静注修饰ＳＯＤ１００００ｕ／ｋｇ，药－时数据符合双室模型，经计算机求出药代动力学参数。修饰ＳＯＤ的分布半衰期和消除半衰期比修饰前延长至１．９和８．６倍。小鼠腹腔注射修饰ＳＯＤ２００ｕ／ｇ，酶活性主要分布于肝和肾，并能通过血脑屏障。     

壮儿饮口服液治疗小儿营养不良临床观察及实验研究

目的 探讨性儿饮口服液治疗小儿营养不良的临床疗效及对模型小鼠红细胞超氧化物歧化酶（ＳＯＤ）活力的影响。方法将１４０例营养不良患儿随机分为２组，分别二儿饮口服液及健脾糖浆，观察临床疗效，并检测治疗前后发锌、血红蛋白的含量，对实验小鼠进行结药前后红细胞ＳＯＤ活力检测。结果 观察组总有效率（８９．７７％）明显高于对照组（６３．４６％），２组比较者显著差异（Ｐ〈０．０５），实验小鼠模型组红细胞ＳＯＤ的活力     

鞘内注射甲氨蝶呤与地塞米松联合口服激素治疗神经精神性狼疮的系统评价

目的：评价鞘内注射甲氨蝶呤（methotrexate,MTX）与地塞米松（dexamethasone,DXM）联合口服激素在神经精神性狼疮（neuropsychiatric systemic lupus erythematosus,NPSLE）治疗中的效果。方法：全面检索1996年1月—2016年12月关于鞘内注射MTX与DXM治疗NPSLE的临床试验文献,采用激素或激素联合环磷酰胺治疗作为对照组,鞘内注射MTX与DXM联合口服激素治疗作为治疗组的随机对照试验进行meta分析。结果：纳入6项研究,256例NPSLE,对照组和试验组的例数分别为126例和130例。meta分析结果显示,治疗组在降低系统性红斑狼疮疾病活动度评分（systemic lupus erythematosus disease activity index,SLEDAI）方面均优于对照组（P<0.01）;并且脑脊液压力、脑脊液蛋白、血沉等相关指标,治疗组均低于对照组（P<0.01）。结论：鞘内注射MTX与DXM联合口服激素的效果优于单纯口服激素;但是由于文献的方法学质量较低,仍需要高质量、大样本、多中心的随机临床试验加以验证。     

人工肝支持系统治疗肝功能衰竭的Meta分析

目的 探讨人工肝支持系统对肝功能衰竭的治疗效果.方法 检索国内外1970年1月～2008年6月公开发表的人工治疗肝功能衰竭的相关论文,提取生存率或出院时临床好转率等可以反映远期预后的资料,以风险比(RR)为效应量进行异质性检验和统计量合计分析.结果 共有12篇研究论文入选,共包含肝功能衰竭病例304例.治疗组给予机械型人工肝或生物型人工肝联合常规内科治疗.对照组均给予常规内科治疗.10篇文献讨论了人工肝对肝功能衰竭的疗效,另两篇探讨了生物肝的应用.总体而言,人工肝支持系统对肝功能衰竭的预后有一定程度的改善(RR值0.80,可信区间0.664～0.969,P值0.022),对急性肝功能衰竭的预后基本无改善(RR值0.899,可信区间0.72～1.12,P值0.361)对慢性肝功能衰竭急性加重患者的预后改善明显.(RR值0.57,可信区间为0.39～0.84,P值为0.004).结论 人工肝支持治疗对肝功能衰竭的生存率改善轻微,对慢性肝功能衰竭急性加重者明显降低死亡率.人工肝支持系统类型影响生存率.生物肝对急性肝衰竭或慢性肝功能衰竭急性加重患者都可以降低死亡率.开发生物肝支持系统应是该领域重点研发方向.

Abstract：

Objective To evaluate the effect of artificial and bioartificial liver support systems for management of acute and acute-on-chronic liver failure. Methods Articles documenting randomized clinical trials concerning any liver support systems vs standard conservative therapy, published between January, 1970 and June, 2008, were retrieved by database searching. Of the 1134 articles retrieved, 12 randomized trials involving 479 patients were included. The data were extracted and the trial quality was assessed by 2 independent reviewers. The primary outcome measure was all-cause mortality, and the results were combined on the risk ratio (RR) scale. Results Of the 12 trials included, 10 assessed artificial liver support systems for acute or acute-on-chronic liver failure, and 2 assessed bioartificial systems for acute liver failure. Overall, the liver support systems had moderate effect on mortality compared with standard conservative therapy (RR=0.80; 95% CI 0.664-0.969, P=0.022).Meta-regression indicated that the effect of the support systems depended on the type of liver failure (P=0.00). In stratified meta-analyses, the support systems appeared to reduce the mortality by 43% in acute-on-chronic liver failure (RR=0.57; 95% CI 0.39-0.84, P=0.004), but not in acute liver failure (RRl=0.899; 95% CI 0.72-1.12, P=0.361). Conclusion Artificial liver support systems reduce the mortality of acute-on-chronic liver failure as compared with standard conservative therapy, but have no significant effect on the mortality of acute liver failure. Bioartificial liver support systems lower the mortality rates in both acute and acute-on-chronic liver failure, and should be the future focus of development.     

糖尿病患者血清,红细胞及尿中超氧化物歧化酶的实验研究

采用ＥＬＩＳＡ法对３７例糖尿病患者及１０４例健康人的血清、红细胞及尿中超氧化物歧化酶（ＳＯＤ）含量进行了检测。结果：糖尿病组血清、红细胞ＳＯＤ含量明显低于正常对照组（Ｐ＜０．０１）；尿ＳＯＤ含量明显高于正常对照（Ｐ＜０．０１）。糖尿病合并血管病变组血清、红细胞ＳＯＤ明显低于不合并血管病变组（Ｐ＜０．０１）；而尿ＳＯＤ则明显高于不合并血管病变组（Ｐ＜０．０１）。血清、红细胞ＳＯＤ与空腹血糖呈负相关，与病程、血酯、血脂酐无相关。尿ＳＯＤ与病程、血肌酐呈正相关，与空腹血糖、血脂无相关。表明：ＳＯＤ在糖尿病及血管病变的发病上起一定作用。尿ＳＯＤ排泄量增加可估计糖尿病肾病的发生及预后。     

复方磷酸盐注射液生产中质量控制探讨

目的复方磷酸盐注射液是医院肠外营养的必备制剂,主要用于肠瘘及其他外科手术后加快创伤愈合,其主要作用是在蛋白合成过程中提供人体所需磷元素。文中介绍复方磷酸盐注射液生产工艺并探讨其生产工艺中与质量相关的关键问题,进一步加强临床用药的安全性。方法对影响复方磷酸盐注射液产品质量的主要流程进行介绍,并对小容量注射剂常见关键质量问题进行研究分析,如可见异物检查、封口、装量、精滤灌封器材。随机抽取3批制剂进行全检。结果复方磷酸盐注射液成品的含量、性状、鉴别、pH值、细菌内毒素、不溶性微粒均符合规定要求。结论所采用的生产工艺稳定、可靠,所制得的注射剂完全符合要求。     

生脉注射液治疗急性心肌梗死后低血压的系统评价

目的 对生脉注射液治疗急性心肌梗死后低血压的疗效与安全性进行系统评价,为临床用药提供循证依据.方法 广泛搜集生脉注射液应用于急性心肌梗死后低血压的临床研究资料,运用Cochrane图书馆系统评价方法对纳入的文献进行质量评价和Meta分析.结果 共纳入5项随机对照试验,Meta分析结果提示生脉注射液与多巴胺联用可取得较单用多巴胺更好的升压效果.收缩压值对比(试验组/对照组)示治疗第1天加权均数差(WMD)为6.02[95%CI( 4.36,7.67)];治疗第2天WMD为9.03[95%CI(6.61,11.45)];治疗第3天WMD为10.99[95%CI(8.43,13.55)].舒张压值对比(试验组/对照组)示治疗第1天WMD为5.03[95%CI(3.72,6.33)];治疗第2天WMD为4.13[95%CI( 2.87,5.40)];治疗第3天WMD为0.97[95%CI(-1.02,2.97)].由于纳入研究的方法学质量低,试验结果有发生偏倚的高度可能性.结论 生脉注射液可能有益于急性心肌梗死后低血压的改善,但目前尚缺乏高质量、大样本的临床数据支持,仍有待进一步研究.     

丹参注射液联合阿司匹林对急性脑梗死患者血清炎性因子水平的影响研究

目的:探讨丹参注射液联合阿司匹林对急性脑梗死患者血清炎性因子水平的影响研究。方法:360例急性缺血性脑梗死患者,数表法随机分为对照组和研究组,每组各180例。两组患者均给予常规治疗。对照组给予阿司匹林肠溶片,口服100 mg/次,1次/d;研究组在给予阿司匹林肠溶片的基础上再给予丹参注射液静脉滴注,1次/d,每两周为1个疗程。两组均治疗两周。治疗结束后,比较两组患者临床疗效、血液流变学指标、血浆同型半胱氨酸(Hcy)、内皮素(ET)、神经元特异性烯醇化酶(NSE)、超氧化物歧化酶(SOD)变化含量、血清白介素-6(IL-6)和肿瘤坏死因子(TNF-α)水平。结果:治疗后,与对照组相比,研究组临床总有效率显著升高(P<0.05)。治疗两周时,与入院时相比,研究组血浆Hcy、ET和NSE水平明显降低(P<0.05),而血浆SOD活性明显升高(P<0.05);与对照组比较,研究组血浆Hcy、ET、NSE及SOD水平降低更明显,血浆SOD活性增加更显著。治疗两周,与入院时和对照组相比,研究组全血浆黏度、全血黏度、红细胞比积、红细胞聚集指数降低更明显(P<0.05)。治疗两周与入院时相比,两组血清IL-6、TNF-α水平均明显降低(P<0.05);与对照组相比,研究组血清中IL-6、TNF-α水平均明显较低(P<0.05)。结论:在急性脑梗死患者中,应用丹参注射液联合阿司匹林肠溶片可以明显改善临床症状,下调炎症因子IL-6、TNF-α水平,血液流变学指标明显改善,适宜临床应用推广。     

茶多酚在对抗石英粉尘所致人群脂质过氧化毒效应中的作用

目的探索茶多酚(TP)在对抗石英粉尘氧化损伤中的作用,为石英粉尘毒作用的预防和控制工作提供参考。方法以外周静脉血红细胞膜谷胱甘肽过氧化物酶(GSH-px)活力、丙二醛(MDA)含量以及超氧化物歧化酶(T-SOD)活力为评价指标,以整群抽样法抽取接触石英粉尘的陶瓷厂健康一线接尘人员107名,抽取厂矿周围居民健康志愿者45名,分别采集静脉血2ml,检测两组人群在利用TP干预前后,红细胞膜SOD活力、MDA含量及GSH-px活力的变化。谷胱甘肽过氧化物酶(GSH-px)活力测定采用二硝基苯甲酸法,丙二醛(MDA)含量测定采用硫代巴比妥法(TBA法),超氧化物歧化酶(T-SOD)活力测定采用黄嘌呤氧化酶法,膜蛋白含量的测定采用考马斯亮蓝法。结果在TP干预后,接尘组人员红细胞膜SOD活力明显回升(P<0·05),MDA含量明显降低(P<0·05),GSH-px活力明显回升(P<0·05),在非接尘组人员中,SOD活力、MDA含量及GSH-px活力三指标变化不明显(P>0·05)。结论TP具有抗石英粉尘所致人红细胞膜脂质过氧化损伤作用。     

银杏叶提取物对老化红细胞膜ATP酶、SOD和MDA影响

目的 观察银杏叶提取物(EGb761)作用下老化红细胞膜三磷酸腺苷酶(ATPase)、超氧化物歧化酶(SOD)和丙二醛(MDA)含量的变化,探讨EGb761抗衰老的机制.方法 采用恒温水浴箱孵育法模拟红细胞的自然衰老过程,观察EGb761对老化红细胞膜MDA含量、SOD和ATPase活性的影响.结果 与衰老组比较,EGb761组的红细胞MDA含量明显降低,SOD、ATPase活性明显升高,差异有极显著意义(t=2.02～70.06,P<0.05、0.001).结论 EGb761能提高红细胞的抗氧化能力,保护红细胞膜蛋白,减缓红细胞的老化过程.     

慢性左心功能不全病人红细胞超氧物歧化酶活性的变化

本文比较了83例不同心功能分级的风湿性心脏病、高血压性心脏病和冠状动脉粥样硬化性心脏病所致慢性左心功能不全患者红细胞超氧物歧化酶(SOD)的活性大小.结果发现,心功能失代偿状态下红细胞 SOD 活性低于心功能代偿者,相同心功能分级的不同病种患者,其 SOD 活性无显著差别.本文认为,慢性左心心功能不全时的缺氧状态是 SOD 活性下降的重要原因,而 SOD 活性的下降可能在一定程度上也促进了心衰的发生与发展.红细胞 SOD 活性的测定有可能作为临床判断心功能是否代偿的指标之一.     

针刺减肥的随机对照试验方法学和报告质量评估

目的评价全世界针刺减肥的随机对照试验的方法学质量和报告质量.方法没有语言限制地系统、全面检索全世界针刺减肥的随机对照试验文献,利用循证医学的质量标准对试验的方法学进行评估;并参照CONSORT和STRICT清单对试验报告的质量进行评估.结果共获得7篇随机对照试验.1篇方法学质量等级为A,2篇方法学质量等级为B,4篇方法学质量等级为C.所有随机对照试验的报告质量等级均为C.结论目前全世界针刺减肥的随机对照试验质量不高,尚不能为临床实践提供强有力的证据.针刺减肥的随机对照试验报告写作质量差,不能充分反映试验所有有用的信息.     

乌司他丁治疗急性颅脑出血临床观察

目的探讨乌司他丁治疗急性颅脑出血的临床效果。方法对124例符合研究对象标准的急性颅脑出血患者,随机分为治疗组和对照组各62例,对照组给予常规治疗,治疗组在常规治疗的基础上,给予静脉滴注乌司他丁50 000 U/kg,1次/d,共用14 d。观察治疗后两组患者白细胞介素10和白细胞介素18及脑水肿指标的变化情况。结果治疗后两组患者白细胞介素10和白细胞介素18炎症指标均有改善,但治疗组更为显著;治疗后两组患者脑水肿指标均有改善,但治疗组更为显著。结论早期应用乌司他丁治疗急性颅脑出血患者疗效肯定。     

Effects of low-dose radiation on tumor growth, erythrocyte immune function and SOD activity in tumor-bearing mice

Radiotherapyandchemotherapyaretheprimarymethodsforthetreatmentofmalignanttumors ;butbothtreatmentscanleadtoinjurybecausetheyinhibitimmunefunction ,andinevitablyinfluencesclinicalresults Somepatientswithmalignanttumorsdieofcomplicationsbecauseofinhibitionofimmunefunction Howtoboostthesepatients’immunesystemhasbecomeanimportanttopicofresearch Reportshaveindicatedthatlow doseradiationhasanexcitatoryeffectonlymphocyteimmunefunction ,1,2 　butfewontheeffectsoflow doseradiationonerythrocyteimmunefu…     

一清胶囊临床研究文献质量评价

目的：对一清胶囊临床研究文献进行质量评价。方法：收集国内1990-2005年6月公开发表的一清胶囊相关论文，按照牛津循证医学中心证据标准和临床试验的设计原则，对文献进行质量评价。结果：推荐级别为B级的占68．4％，C级占31．6％；证据水平为2b级占26．3％，3b级占42．1％，4级占31．6％：随机对照试验文献占68．4％，临床对照占5.3％。随机双盲占3．8％；说明组间基线可比性的占11．5％，有诊断标准的占26．9％，有纳入和排除标准占11．5％，说明统计学方法的占19．2％，有客观疗效评价指标占50．0％，说明药物不良反应占3．8％。结论：一清胶囊的临床研究较为活跃，但随机对照试验质量偏低，临床研究设计需进一步规范，论文撰写水平有待提高。