双歧杆菌三联活菌胶囊/散治疗新生儿黄疸临床疗效的Meta分析

摘要：目的 采用Meta分析方法评价双歧杆菌三联活菌胶囊/散治疗新生儿黄疸的临床疗效。方法 计算机检索中国知网、万方、维普、Pubmed、Embase、Web of Science数据库,检索时限均从建库至2015年12月,收集国内外应用双歧杆菌三联活菌胶囊/散治疗新生儿黄疸的所有随机对照试验（randomized controlled trial,RCT）和前瞻性非随机对照试验（non-randomized controlled trial,non-RCT）,纳入文献时间从2001年1月至2014年12月不等。按照纳入与排除标准选择文献、提取资料并评价质量后,采用Cochrane协作网提供的RevMan 5.2软件进行Meta分析。结果 检索文献无RCT研究,纳入17篇前瞻性non-RCT研究文献,合计1988例患者,其中治疗组（对照组常规治疗措施+双歧杆菌三联活菌胶囊/散）1 004例,对照组984例。Meta分析结果显示：治疗组的有效率优于对照组［OR=3.36,95%CI（2.14,5.27）,P<0.001］;治疗组新生儿黄疸持续天数低于对照组［Mean Deviation（MD）=-2.13,95%CI（-2.63,-1.62）,P<0.001］;治疗后第3天经皮胆红素值治疗组低于对照组［MD=-29.66,95%CI（-42.78,-16.54）,P<0.001］。结论 双歧杆菌三联活菌胶囊/散与常规治疗措施联用可以提高新生儿黄疸的总体疗效,同时可以有效减少新生儿黄疸的持续天数,加快黄疸的消退。     

我院自制5号粉对宫颈糜烂并HPV感染的临床疗效

目的：分析我院自制5号粉对宫颈糜烂并HPV（人乳头瘤病毒）感染是否具有临床疗效。方法：选择我院妇科就诊并自愿接受fI盏床实验的90例宫颈糜烂并HPV患者（呈阳性）,按照随机数表法,进行随机分组,分别是中药组与西药组,平均每组患者45例。对两组患者分别使用中药组方与西药两种不同药物进行治疗。治疗后,参照相关疗效评价标准,对两组患者治疗的总有效率及总计转阴率进行比较分析。结果：治疗后,发现中药组患者治疗的总有效率为84．33％,西药组治疗的总有效率为59％,中药组治疗的临床疗效明显优于西药组,两组比较有统计学意义（P〈0．05）。中药组患者的3个月,6个月,12个月的转阴率分别为45．7％,62．3％,75．7％,西药组治疗的转阴率为21．0％,37．7％,47．7％,中药组治疗的临床疗效明显优于西药组,两组比较有统计学意义（P〈0．05）。结论：通过临床观察分析得我院自制5号粉对宫颈糜烂并HPV（人乳头瘤病毒）感染具有临床治疗效果,可以提高HPV（人乳头瘤病毒）的转阴率,并且极大缩短转阴时间。     

硝苯地平缓释片联合缬沙坦治疗原发性高血压疗效和安全性的Meta分析

目的：系统评价硝苯地平缓释片联合缬沙坦治疗原发性高血压的疗效和安全性。方法：计算机检索PubMed、CochraneLi-brary、CBM、CNKI、V1P等数据库,按照纳入和排除标准纳入依硝苯地平缓释片联合缬沙坦治疗原发性高血压的随机对照试验（RCT）,并补充检索纳入研究的参考文献;按Cochrane系统评价方法由两名评价员独立评价纳入文献质量、提取资料并交叉核对无误后,采用RevMan5．1软件进行统计学分析。结果：共纳入4个RCT,包括共450例患者,其研究质量均为C级。Meta分析结果显示：硝苯地平缓释片联合缬沙坦治疗原发性高血压的显效率[RR=1．29,95％CI（1．08～1．55）,P〈O．011、总有效率[RR=I．19,95％CI（1．10～1．29）,P〈0．01]和无效率[RR=0．38,95％CI（0．24～0．62）,P〈0．01]与单用硝苯地平缓释片比较,两组差异有统计学意义,两组有效率差异无统计学意义[RR=I．02,95％CI（0．97～1．32）,P〉0．01]。结论：现有证据表明：硝苯地平缓释片联合缬沙坦治疗原发性高血压在显效率,总有效率和无效率方面优于硝苯地平缓释片单用,不良反应与苯地平缓释片单用无明显差异,但远期疗效尚不清楚,尚需更多高质量的随机双盲对照试验证实。     

胃食管反流病中安慰剂反应率的相关研究

目的：对胃食管反流病（GERD）随机对照试验中的安慰剂反应率进行Meta分析并研究影响该反应率的因素。方法：检索EMBASE,CochraneControlledTrialRegister和Medline数据库中公开发表的关于双盲、随机、安慰荆对照治疗GERD的英文文献,所有文献均包括质子泵抑制剂／H2受体阻滞剂,治疗时间至少为2周。对文献试验数据进行Meta分析,绘制森林图,同时绘制漏斗图检查发表偏倚。结果：纳入24个研究,共包括8917名患者。有效治疗的反应率与安慰剂反应率相比的OR为3．70（95％CI：2．77～4．95）。所有的安慰剂反应率为18．84％（2．93％-47．05％）。运用质子泵抑制剂治疗的患者与H：受体阻滞剂治疗者相比,安慰剂反应率明显降低（14．50％vs．24．68％,P=0．05）。糜烂性食管炎患者的安慰剂反应率与非糜烂性食管炎者相比略低,两者差异无显著性（P〉0．05）。结论：在GERD随机对照试验中,安慰剂反应率确实存在。该反应率降低与质子泵抑制剂的运用相关,而与腐蚀性食管炎的存在与否无关。     

氨氯地平和硝苯地平临床治疗高血压的有效性与安全性的Meta 分析

目的：探讨氨氯地平和硝苯地平临床治疗高血压的有效性与安全性。方法：计算机检索中国知网、维普资讯网和万方数据库,收集1990—2013 年间国内公开发表的关于氨氯地平和硝苯地平治疗高血压的随机对照试验文献资料,并根据纳入和排除标准,对其进行筛选;采用Stata 12.0 软件对纳入文献中临床试验数据进行Meta 分析。结果：共筛选出23 篇文献。纳入文献中氨氯地平和硝苯地平治疗高血压的有效性Meta 分析结果显示,两药物治疗组有效性总体数据的OR 为2.71（95%CI：2.07,3.55）,且P ＜ 0.01,即氨氯地平组的总有效率显著高于硝苯地平组;安全性Meta 分析结果显示,两药物治疗组安全性总体数据的OR 为0.36（95%CI：0.28,0.47）,且P ＜ 0.01,即氨氯地平组的总不良反应发生率显著低于硝苯地平组。结论：与硝苯地平相比,氨氯地平临床治疗高血压更有效、更安全。     

非索非那定治疗变应性鼻炎的随机对照试验的Meta分析

目的：评价非索非那定治疗变应性鼻炎的疗效及其安全性。方法：计算机检索SCI,Pubmed,Elsevier,Cochrane图书馆,知网,万方数据库,维普数据库中关于非索非那定治疗变应性鼻炎的随机对照试验,同时追索纳入文献的参考文献。检索年限均从建库检索到2013年12月。由两名评价员独立筛查文献,对纳入的文献进行质量评价并提取文献,对符合质量标准的随机对照试验（RCT）进行Meta分析,比较非索非那定组和安慰剂组鼻部症状评分、血清中白三烯浓度、生活质量评价、症状改善率和安全性评估。统计学分析采用RevMan5．2软件。结果：共纳入9个RCT。患者口服非索非那定片30mg／d,120mg／d,180mg／d后可有效改善变应性鼻炎患者的症状,可降低患者鼻部症状评分、血清中白三烯浓度;有效提高生活质量,降低患者总的生活质量评分（P均〈0．05）。非索非那定不良反应的发生率与安慰剂组相似,不良反应发生率差异无统计学意义（P〉0．05）。结论：患者口服非索非那定片30mg／d,120mg／d,180mg／d后可以有效缓解患者的症状,改善患者的生活质量,且不良反应发生率与对照组相近。基于非索非那定较好的有效性和安全性,故可以广泛应用于临床,更加有效的缓解变应性鼻炎患者的症状。     

脑心通胶囊辅助治疗不稳定型心绞痛的临床疗效和安全性的Meta分析

目的：系统评价脑心通胶囊辅助治疗不稳定型心绞痛的临床疗效及其安全性。方法：计算机检索PubMed（1966-2012．3）、EMbase（1974-2012.3）、CochraneLibrary（2012年第3期）、CBM（1978-2012．3）、CNKI（1994-2012．3）、VIP（1989-2012．3）。纳入脑心通胶囊联合常规药物治疗不稳定型心绞痛的随机对照试验（RCT）,并补充检索纳入研究的参考文献;按Cochrane系统评价方法对纳入研究进行资料提取及质量评估后,采用RevMan5．1软件进行统计学分析。结果：共纳入11个RCT,包括共1384例患者,Meta分析结果显示：与常规药物治疗相比,脑心通胶囊联合常规药物明显缓解不稳定型心绞痛患者的临床症状,差异有统计学意义[RR=1．24,95％CI（1．18-1．31）,P〈0．01],提高了心电图的改善率[RR=1．35,95％CI（1．24-1．47）,P〈0．01]。结论：目前研究表明脑心通胶囊辅助治疗不稳定型心绞痛的短期疗效明显优于常规治疗,但其不良反应和远期疗效尚不确定,需要更多高质量随机对照试验进一步证实。     

双歧杆菌三联活菌胶囊/散治疗儿童功能性便秘临床疗效的Meta分析

目的采用Meta分析评价双歧杆菌三联活菌胶囊/散治疗儿童功能性便秘的临床疗效。方法检索中国知网、万方、维普、Pubmed、Embase、Web of Science数据库,检索时限均从建库至2015年12月,收集国内外应用双歧杆菌三联活菌胶囊/散治疗儿童功能性便秘的所有随机对照试验(randomized controlled trial,RCT)和前瞻性非随机对照试验(non-randomized controlled trial,non-RCT),纳入文献时间从2005年1月至2013年12月。按照纳入与排除标准选择文献,进一步提取纳入研究的资料并评价其方法学质量后,采用Cochrane协作网提供的RevMan 5.2软件进行Meta分析。结果检索文献无RCT研究,纳入9个前瞻性non-RCT研究,合计673例患者,其中治疗组(对照组常规治疗+双歧杆菌三联活菌胶囊/散)345例,对照组328例。Meta分析结果显示:治疗组的治疗有效率优于对照组[OR=4.81,95%CI=(2.32,9.97),P0.0001];治疗组儿童功能性便秘复发率低于对照组[OR=0.19,95%CI(0.05,0.68),P=0.01]。结论双歧杆菌三联活菌胶囊/散与常规治疗药物联用可以提高儿童功能性便秘的总体疗效,同时可以有效降低儿童功能性便秘的复发率。     

红景天类药物治疗心绞痛的系统评价

目的：评价红景天类药物治疗心绞痛的疗效和不良反应。方法：电子检索MEDLINE、EMBASE、中国生物医学文献数据库、中文科技期刊全文数据库和中文学术期刊全文数据库,并手工检索相关杂志,检索日期截止至2006年2月。纳入以心绞痛患者为研究对象、比较红景天类药物与其它药物治疗效果的随机对照试验。评价纳入研究的质量,并用RevMan4．2．8软件进行Meta分析。结果：共纳入8个研究,合计样本量894例。红景天类药物在心绞痛临床症状、心电图、中医证候及硝酸甘油停减率方面的疗效均优于其它治疗用药,其汇总OR分别为2．44（95％CI1．67—3．58）、1．42（95％CI1．06—1．89）、2．04（95％CI1．27—3．29）和1．88（95％CI1．25—2．83）。未发现明显的不良反应。结论：红景天类药物在心绞痛临床症状、心电图、中医证候及硝酸甘油停减率方面的疗效显示出比其它治疗用药更加有效的倾向,尚需更多高质量研究以增加证据的强度。     

系统评价中西医结合治疗单纯疱疹病毒性角膜炎的疗效

为评价中西医结合治疗单纯疱疹病毒性角膜炎的疗效,检索万方、维普、知网等国内中文数据库2005—2018年所有采用中西医结合治疗单纯疱疹病毒性角膜炎的随机对照试验,筛选合格文献并提取相关信息进行分析,将符合纳入标准的研究采用Revman 5.3软件进行方法学质量评价、Meta-分析、漏斗图分析、异质性检验及偏倚风险评估。最终纳入15篇研究,共1 521例患者,Meta分析结果显示:中西医结合对比单纯西医治疗单纯疱疹病毒性角膜炎,总有效率高[OR=5.23,95%,CI(3.51,7.80),P0.000 01];复发率低[OR=0.32,95%CI(0.22,0.45),P0.000 01],治愈时间短[MD=-5.40,95%,CI(-6.41,-4.40),P0.000 01],差异均具有显著的统计学意义。研究显示,中西医结合治疗单纯疱疹病毒性角膜炎的疗效优于单纯用西药治疗单纯疱疹病毒性角膜炎,具有很好的临床应用前景。     

间充质干细胞基础研究与临床转化的中美比较

目的：从基础研究、专利申请、临床试验角度对比分析中美间充质干细胞领域发展现状和趋势,了解中美间充质干细胞领域研究的主要特征,为中国间充质干细胞领域的发展提供建议。方法：检索SCI论文数据、DII专利数据及Clinical Trials临床试验数据及新药审批情况,利用Excel、DDA工具对检索结果进行定量分析和讨论。结果：中国在间充质干细胞基础研究、专利申请及临床试验方面虽起步较晚,但近年来发展迅速,论文、专利和临床试验数量快速增长,2014年起发表论文数量及2016年申请专利数量均超过美国,临床试验注册已达200余项;在骨质疏松、脊髓损伤等研究领域,内分泌系统疾病、自体免疫疾病等临床试验方面形成一定优势,已具备坚实的团队与技术基础。但我国间充质干细胞研究仍面临激烈的竞争,存在进步与发展空间。结论：我国间充质干细胞研究应发挥已有优势,加强战略性布局;重视发展以企业为主导的新药开发路径;做精做细以增强国际竞争力与影响力;加大资金投入和产业政策的支持;健全监管机制及评价体系,抓住机遇的同时积极迎接挑战。     

Evaluation of the anti-fatigue effects of a traditional herbal drug,Gongjin-dan,under insufficient sleep conditions: study protocol for a randomised controlled trial

BackgroundMany herbal medicines are traditionally used as anti-fatigue agents in east Asian countries; however, there is a dearth of clinical evidence supporting the anti-fatigue effects of such medicines and their mechanisms. This study is a feasibility trial to assess the clinical efficacy of Gongjin-dan (GJD) and verify its mechanisms by exploring fatigue outcomes, including endocrine and immunological biomarkers in humans.Methods/DesignTo investigate the anti-fatigue effects of GJD and the mechanism underlying these effects, a randomised, double-blind, placebo-controlled crossover clinical trial was designed. Participants (24 healthy male volunteers) will be hospitalised for 4 days (3 nights), during which acute fatigue and stress conditions will be induced by sleep deprivation, and GJD or a placebo will be administered (twice daily). The primary outcome will be changes in serum cortisol levels, measured in the morning, as an objective biomarker of sleep deprivation-induced fatigue and stress. The secondary outcomes will include: the Fatigue Severity Scale; the Brief Fatigue Inventory, and the Leeds Sleep Evaluation Questionnaire scores; levels of salivary cortisol, epinephrine, norepinephrine, oxidative stress-related biomarkers, homocysteine, and immunological factors; and heart rate variability. After a washout period of more than 4 weeks, a second treatment phase will commence in which participants who were previously administered the placebo will receive the drug and vice versa, following the same treatment regime as in the first phase.DiscussionThis study protocol provides a unique opportunity to enhance our understanding of fatigue and the effects of GJD on fatigue in terms of endocrine and immunological mechanisms by validating the study design and determining feasibility. Findings from this trial will help researchers to design a pilot or definitive clinical trial of traditional herbal medicine for chronic fatigue.

Trial registration

Korean National Clinical Trial Registry CRIS; KCT0001681, registered on 29 October 2015.     

Stem cell therapies and regenerative medicine in China

Stem cells are the core of tissue repair and regeneration,and a promising cell source for novel therapies.In recent years,research into stem cell therapies has been particularly exciting in China.The remarkable advancements in basic stem cell research and clinically effective trials have led to fresh insights into regenerative medicine,such as treatments for sweat gland injury after burns,diabetes,and liver injury.High hopes have inspired numerous experimental and clinical trials.At the same time,government investment and policy support of research continues to increase markedly.However,numerous challenges must be overcome before novel stem cell therapies can achieve meaningful clinical outcomes.     

The survey on cellular and tissue-engineered therapies in Europe and neighboring Eurasian countries in 2014 and 2015

Background aims

With the support of five established scientific organizations, this report, the seventh of its kind, describes activity in Europe for the years 2014 and 2015 in the area of cellular and tissue-engineered therapies, excluding hematopoietic stem cell (HSC) treatments for the reconstitution of hematopoiesis.

Peripheral blood-derived autologous stem cell therapy for the treatment of patients with late-stage peripheral artery disease—results of the short- and long-term follow-up

Background aimsRegeneration of the occluded peripheral arteries by autologous stem cell therapy is an emerging treatment modality for no-option patients with peripheral artery disease (PAD). The purpose of this study was to assess safety and efficacy of in vitro–expanded, peripheral blood-derived, autologous stem cells (VesCell) in no-option patients with PAD.MethodsA phase II, open-label, randomized clinical study was performed on 20 patients to investigate the safety and efficacy of VesCell therapy at 1 and 3 months of follow-up. The long-term (2 years) efficacy of the therapy was also evaluated.ResultsNo side effects of VesCell therapy were found. During the 3 month follow-up in the control group, one death occurred and six major amputations were performed; in the treated group, there were no deaths or major amputations. The difference of limb loss is significant between the two groups. At 2-year follow-up in the control group, two deaths and six major amputations occurred; in the treated group, there were three major amputations. At 3-month follow-up, the change in hemodynamic parameters showed a significant increase in the treated group over the control group; in the treated group, further improvement was detected at 2 years. As the result of the VesCell treatment, change in pain score, wound healing and walking ability test showed an improvement compared with the control group; at 2 years, incremental improvement was observed.ConclusionsPeripheral blood-derived, in vitro–expanded autologous angiogenic precursor therapy appears to be a safe, promising and effective adjuvant therapy for PAD patients.     

Designing precision medicine trials to yield a greater population impact

Traditionally, a clinical trial is conducted comparing treatment to standard care for all patients. However, it could be inefficient given patients’ heterogeneous responses to treatments, and rapid advances in the molecular understanding of diseases have made biomarker-based clinical trials increasingly popular. We propose a new targeted clinical trial design, termed as Max-Impact design, which selects the appropriate subpopulation for a clinical trial and aims to optimize population impact once the trial is completed. The proposed design not only gains insights on the patients who would be included in the trial but also considers the benefit to the excluded patients. We develop novel algorithms to construct enrollment rules for optimizing population impact, which are fairly general and can be applied to various types of outcomes. Simulation studies and a data example from the SWOG Cancer Research Network demonstrate the competitive performance of our proposed method compared to traditional untargeted and targeted designs.     

No effect of a traditional Chinese medicine, Hochu-ekki-to, on antibody titer after influenza vaccination in man: A randomized, placebo-controlled, double-blind trial

BACKGROUND: It was shown that a traditional Chinese medicine, Hochu-ekki-to (HET), had adjuvant effects in influenza vaccination in an animal experiment. This, however, could not be assessed in a clinical study. METHODS: Thirty-two healthy subjects were randomly assigned to two groups (control and HET groups) in a double-blind manner. HET subjects (n=17) took 7.5 g of HET/day for two weeks; control subjects took the same amount of indistinguishable placebo. Then subjects were vaccinated against influenza (H1N1, H3N2 and B/Shandong). Hemagglutinin titers and natural killer (NK) activity were measured at weeks 0, 1, 2, 4, and 12. RESULTS: Antiinfluenza titers against the three viruses were increased continuously for the first two weeks and leveled off. However, there were no significant differences in any titers between the two groups. NK activity peaked at week 2 without any inter-group differences. CONCLUSION: We could not find any adjuvant effects of HET in this experimental condition.     

Adaptive enrichment designs with a continuous biomarker

A popular design for clinical trials assessing targeted therapies is the two-stage adaptive enrichment design with recruitment in stage 2 limited to a biomarker-defined subgroup chosen based on data from stage 1. The data-dependent selection leads to statistical challenges if data from both stages are used to draw inference on treatment effects in the selected subgroup. If subgroups considered are nested, as when defined by a continuous biomarker, treatment effect estimates in different subgroups follow the same distribution as estimates in a group-sequential trial. This result is used to obtain tests controlling the familywise type I error rate (FWER) for six simple subgroup selection rules, one of which also controls the FWER for any selection rule. Two approaches are proposed: one based on multivariate normal distributions suitable if the number of possible subgroups, k, is small, and one based on Brownian motion approximations suitable for large k. The methods, applicable in the wide range of settings with asymptotically normal test statistics, are illustrated using survival data from a breast cancer trial.     

中西医结合治疗脂肪肝64 例临床观察

目的:探讨中西医结合治疗脂肪肝的临床疗效。方法:将64例患者随机分为治疗组和对照组,其中治疗组43例患者在西药治疗的基础上加入HD肝病治疗仪经络穴位中药局部导入;对照组采用西药治疗。结果:两组临床疗效总有效率、血生化改变、B超、CT、影像学改变总有效率经统计学处理,P<0.05,有显著差异;治疗组优于对照组。结论:临床治疗观察表明,运用此法配合西药营养肝细胞改善代谢,发挥中西医的协同作用,疗效明显优于单纯运用西药。     

精准医学时代的抗肿瘤药物研发

自 2015 年初,美国总统奥巴马在国情咨文中提出了“精准医学计划”,精准医学迅速成为全球医学界热议和关注的焦点。精准医 学改变了人们对于疾病,特别是肿瘤的药物开发、临床试验和治疗策略的认识和工作模式。2016 年美国通过的《21 世纪治愈法案》进一 步强化了精准医学在药物开发中的作用。重点介绍精准医学在肿瘤药物研发领域引起的变革与发展情况,并就精准医学的现状和前景作深 入探讨。