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| 1 | GRADE指南:Ⅴ.证据质量评价--发表偏倚显示文摘GRADE方法中,随机试验起评即为高质量证据,观察性研究起评即为低质量证据;但若证据本身存在高发表偏倚风险,则两者证据质量级别都应降低。即使最佳证据汇总表纳入的各项研究仅有低发表偏倚风险,发表偏倚仍会极大高估效应值。当可得证据来自小样本研究、且多数由厂商资助时,作者应怀疑存在发表偏倚。若干基于检验数据类型的方法可用于评价发表偏倚,其中最常用的为漏斗图,但这些方法都有较大局限。发表偏倚可能较常见,必须特别关注早期结果、对样本量与事件数都很小的早期试验结果尤需小心。 | Gordon H.Guyatt Andrew D.Oxman Victor Montori Gunn Vist Regina Kunz Jan Brozek Pablo Alonso-Coello Ben Djulbegovic David Atkins Yngve Falck-Ytter John W.Williams Jr. Joerg Meerpohl Susan L.Norris Elie A.Akl Holger J.Schünemann 代表GRADE工作组 李幼平 王莉 钟大可 蒋兰慧 | 2011 | 中国循证医学杂志2011，11，12： | 71 |
| 2 | GRADE:证据质量和推荐强度分级的共识显示文摘GRADE工作组致中国读者:推荐分级的评估、制定与评价(GRADE)工作组已取得长足进步。我们制定了系列指南文件,除发表文章外,该非正式组织已经发展成为一个评价证据、转化卫生保健领域知识用以指导决策者的智囊团。80余位国际专家研究和制定了该评价系统。正如其他科学一样,证据评价和指南制定科学不会停滞不前。经过十年发展,GRADE的工作将借助中国Cochrane中心的推广在中国的卫生保健领域更加广为人知。GRADE工作组的成员期待与中国的指南制定组织、方法学家、临床医生和决策者合作,实现我们的共同目标:人人享有更好的卫生保健。中国Cochrane中心翻译GRADE工作组在BMJ上发表的系列文章,是朝这个方向迈出的重要一步,也是对下一步在中国推广GRADE工作的直接贡献。感兴趣的读者可登录我们的网站www.gradeworkinggroup.org和在以下网址获取我们的软件GRADEprohttp://gffzz73f9075754ca43bbh6ouxbkkbubxb6qwn.ffgz.tsg.suse.edu.cn. | Gordon H Guyatt Andrew D Oxman Gunn E Vist Regina Kunz Yngve Falck-Ytter Pablo Alonso-Coello Holger J Schünemann GRADE工作组 陈佩贤 陈耀龙 李幼平 | 2009 | 中国循证医学杂志2009，9，1： | 60 |
| 3 | GRADE指南:Ⅳ.证据质量分级--研究的局限性(偏倚风险)显示文摘在GRADE方法中,若多数相关证据来自高偏倚风险的研究,则起初被定为高质量证据的随机试验和低质量证据的观察性研究均有可能被降低质量等级。随机试验已确定的局限性包括:未进行分配隐藏、未实施盲法、未报告失访情况及未恰当考虑意向性治疗原则。最近提出的局限性包括:因明显获益而早期终止试验和基于结果选择性报告结局。观察性研究的主要局限性包括使用不合适的对照及未能充分调整预后的不平衡。偏倚风险可因不同结果而异(如全死因死亡率的失访远少于生命质量的失访),许多系统评价都容易忽略这一点。在决定是否因偏倚风险而降低质量等级时,不管是随机试验还是观察性研究,作者不应采用对各个研究取平均值的方法。相反,对任何单个结果,当同时存在高、低偏倚风险的研究时,则应考虑只纳入较低偏倚风险的研究。 | Gordon H.Guyatt Andrew D.Oxman Gunn Vist Regina Kunz Jan Brozek Pablo Alonso-Coello Victor Montori Elie A.Akl Ben Djulbegovic Yngve Falck-Ytter Susan L.Norris John W.Williams Jr. David Atkins Joerg Meerpohl Holger J.Schünemann GRADE工作组 李幼平 杨晓妍 李鸿浩 李玲 | 2011 | 中国循证医学杂志2011，11，4： | 58 |
| 4 | GRADE指南:Ⅵ.证据质量评价--不精确性(随机误差)显示文摘GRADE建议通过检查95%可信区间(CI)为决定不精确性的最佳方法。在指南实际运用中,如果CI的上、下限值代表了真实效应,而临床实际情况与之不符时,必须降低证据质量级别(即对效应估计值的把握度)。除外当效应值很大且可信区间提示效应稳健,而总样本量不大且事件数很少的情况,其他应考虑因不精确性而降低证据质量级别。作此决定时,可计算有足够检验效能的单个试验所需的病例数(定义为'最优信息样本量',即optimal information size,OIS)。对连续型变量,我们建议用类似方法,首先考虑可信区间上、下限值,再计算OIS。系统评价(SR)所需方法略有不同。如果95%CI不包括相对危险度(RR)为1,且总事件发生数或病例数超过OIS标准,则精确性良好。如果95%CI包括了明显获益或危害(我们建议以RR值<0.75或>1.25作粗标准),即使达到OIS要求,因不精确性而降低证据质量级别较恰当。 | Gordon Guyatt Andrew D.Oxman Regina Kunz Jan Brozek Pablo Alonso-Coello David Rind PJ Devereaux Victor M.Montori Bo Freyschuss Gunn Vist Roman Jaeschke John W.Williams Jr. Mohammad Hassan Murad David Sinclairk Yngve Falck-Ytter Joerg Meerpohl Craig Whittington Kristian orlund Je Andrews Holger J.Schünemann 代表GRADE工作组 李幼平 王莉 陈尹 高霑 | 2011 | 中国循证医学杂志2011，11，12： | 43 |
| 5 | Chemokines and Chemokine Receptors:Their Manifold Roles in Homeostasis and Disease显示文摘Chemokines are a superfamily of small proteins that bind to G protein-coupled receptors on target cells and were originally discovered as mediators of directional migration of immune cells to sites of inflammation and injury. In recent years, it has become clear that the function of chemokines extends well beyond the role in leukocyte chemotaxis. They participate in organ development, angiogenesis/angiostasis, leukocyte trafficking and homing, tumorigenesis and metastasis, as well as in immune responses to microbial infection. Therefore,chemokines and their receptors are important targets for modulation of host responses in pathophysiological conditions and for therapeutic intervention of human diseases. | Pablo Iribarren | 2004 | Cellular & Molecular Immunology2004，1，2： | 35 |
| 6 | GRADE指南:Ⅶ.证据质量评价--不一致性显示文摘本文针对二分类变量结局指标相对(而非绝对)治疗效果的不一致性。证据本身不会因不同研究结果具有一致性而升级,但可能因不一致而降低质量级别。衡量一致性的标准包括点估计值的相似性、可信区间的重叠程度以及统计学判定标准包括异质性检验和I2。系统评价作者应提出并检验少数几个与患者、干预措施、结局指标以及方法学相关的先验假设以探寻异质性来源。当不一致性很大且无法解释时,因不一致性而降低质量级别是恰当的,特别当某些研究显示有显著益处而其他显示无益甚至有害时(而非仅是疗效大与疗效小的比较)。明显的亚组效应可能不可靠。如果亚组效应满足以下条件,其可信度将会增加:基于少数几个有具体方向的先验假设、亚组比较来自研究内而非研究间、交互检验的P值小、结果有生物学意义。 | Gordon H.Guyatt Andrew D.Oxman Regina Kunz James Woodcock Jan Brozek Mark Helfand Pablo Alonso-Coello Paul Glasziou Roman Jaeschke Elie A.Akl Susan Norris Gunn Vist Philipp Dahm Vijay K.Shukla Julian Higgins Yngve Falck-Ytter Holger J.Schünemann 代表GRADE小组 李幼平 杨晓妍 王莉 蔡羽嘉 陈群飞 | 2011 | 中国循证医学杂志2011，11，12： | 33 |
| 7 | Beneficial effects of naringenin in liver diseases: Molecular mechanisms显示文摘Liver diseases are caused by different etiological agents, mainly alcohol consumption, viruses, drug intoxication or malnutrition. Frequently, liver diseases are initiated by oxidative stress and inflammation that lead to the excessive production of extracellular matrix(ECM), followed by a progression to fibrosis, cirrhosis and hepatocellular carcinoma(HCC). It has been reported that some natural products display hepatoprotective properties. Naringenin is a flavonoid with antioxidant, antifibrogenic, anti-inflammatory and anticancer properties that is capable of preventing liver damage caused by different agents. The main protective effects of naringenin in liver diseases are the inhibition of oxidative stress, transforming growth factor(TGF-β) pathway and the prevention of the transdifferentiation of hepatic stellate cells(HSC), leading to decreased collagen synthesis. Other effects include the inhibition of the mitogen activated protein kinase(MAPK), toll-like receptor(TLR) and TGF-β non-canonical pathways, the inhibition of which further results in a strong reduction in ECM synthesis and deposition. In addition, naringenin has shown beneficial effects on nonalcoholic fatty liver disease(NAFLD) through the regulation of lipid metabolism, modulating the synthesis and oxidation of lipids and cholesterol. Moreover, naringenin protects from HCC, since it inhibits growth factors such as TGF-β and vascular endothelial growth factor(VEGF), inducing apoptosis and regulating MAPK pathways. Naringenin is safe and acts by targeting multiple proteins. However, it possesses low bioavailability and high intestinal metabolism. In this regard, formulations, such as nanoparticles or liposomes, have been developed to improve naringenin bioavailability. We conclude that naringenin should be considered in the future as an important candidate in the treatment of different liver diseases. | Erika Hernández-Aquino Pablo Muriel | 2018 | World Journal of Gastroenterology2018，24，16： | 31 |
| 8 | GRADE指南:Ⅷ.证据质量评价--间接性显示文摘直接证据来自直接比较我们关注的干预措施用于我们关注的患者人群,并测量患者重要结局的研究。间接证据可由以下4种方式之一产生。第一,患者可能与我们关注的患者不同(适用性一词常用于这类间接性)。第二,所检验的干预措施可能与我们关注的干预措施不同。有关患者和干预措施间接性的决策取决于对生物或社会因素差异是否大到可能使效应尺度出现预期的较大差异的考虑。第三,结果可能有别于最初设定的结局指标——如替代结果本身不重要,但测量之是基于替代结果的变化反映患者重要结局变化这一假设。第四类间接性在概念上与前三类不同,发生于临床医生必须在未经直接比较的两种干预措施间做出选择时。这种情况下比较治疗方案需要特定的统计方法,并根据患者人群、联合干预措施、结局测量指标及备选干预措施试验方法的差异程度,将证据级别降低1或2级。 | Gordon Guyatt Andrew D.Oxman Regina Kunz James Woodcock Jan Brozek Mark Helfand Pablo Alonso-Coello Yngve Falck-Ytter Roman Jaeschke Gunn Vist Elie A.Akl Piet N Post Susan Norris Joerg Meerpohl Mona Nasser 代表GRADE工作组 李幼平 杨晓妍 李鸿浩 | 2011 | 中国循证医学杂志2011，11，12： | 30 |
| 9 | 指南2.0:为成功制定指南而系统研发的全面清单显示文摘背景虽然当前已有一些评估卫生保健指南可靠性的工具,但仍缺乏针对制定指南实际步骤的指导。针对指南制定者们所需考虑的相关资源和工具,我们系统研发了一份全面的条目清单,但这并不意味着每篇指南都需遵守该清单的所有条目。方法我们检索了国际指南制定机构的指南制定手册、指南的指南(主要是来自国际和国家机构以及专业学会的方法学报告),以及提供系统指导的最新文章。经过反复评价这些资料,尽可能全面地罗列和提取条目,并制定与指南有关的重要主题。通过反复讨论,我们对条目进行评价以去重和补漏,同时邀请指南制定专家对所增加的条目进行修改并提出建议。结果我们制定了一份包含18个主题、146个条目的清单,并建立了帮助指南制定者应用这些条目的网站。这些主题和条目涵盖了指南从规划、完成、实施和评估的全过程。最终的清单版本也包括了培训所需的资料以及应用这些条目时用到的方法学参考文献的链接。解释本清单将提供给指南制定者用作参考。仔细考虑清单中的条目将有助于指南的制定、实施和评估,我们也将会通过大众反馈来修订并持续更新清单。 | Holger J. Schunemann Wojtek Wiercioch Itziar Etxeandia Maicon Falavigna Nancy Santesso Reem Mustafa Matthew Ventresca Romina Brignardello-petersen] Kaja-Triin Laisaar Sergio Kowalski Tejan Baldeh Yuan Zhang Uiia Raid Ignacio Neumann Susan L. Norris Judith Thornton Robin Harbour Shaun Treweek Gordon Guyatt Pablo Alonso-Coello Marge Reinap Jan Brozek Andrew Oxman Elie A. Akl | 2014 | 中国循证医学杂志2014，14，9： | 26 |
| 10 | GRADE指南:Ⅸ.证据质量升级显示文摘证据质量升级的最常见原因是效应量大。当方法学严谨的观察性研究表明风险至少降低或增加2倍时,GRADE建议考虑将证据质量升高1级;当风险至少降低或增加5倍时,考虑将证据质量升高2级。当存在剂量-反应关系,或所有合理的混杂、偏倚会降低明显的治疗效应,或混杂、偏倚使得结果无效为假效应时,系统评价作者和指南制定者也可考虑升高证据质量。其他考虑因素包括起效迅速、潜在的疾病(状态)趋势以及间接证据。 | Gordon H.Guyatt Andrew D.Oxman Shahnaz Sultan Paul Glasziou Elie A.Akl Pablo Alonso-Coello David Atkins Regina Kunz Jan Brozek Victor Montori Roman Jaeschke David Rind Philipp Dahm Joerg Meerpohl Gunn Vist Elise Berliner Susan Norris Yngve Falck-Ytter M.Hassan Murad Holger J.Schünemann 代表GRADE工作组 李幼平 杨晓妍 李玲 王应强 | 2011 | 中国循证医学杂志2011，11，12： | 22 |
| 11 | New Insights into Plant Isoprenoid Metabolism显示文摘Isoprenoids are a hugely diverse family of compounds derived from the C5 precursors isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP).Although all free-living organisms synthesize isoprenoids,they are particularly abundant and diverse in plants,with tens of thousands structures known to date.The highest variety of plant isoprenoids are specialized (secondary) metabolites that participate in the interaction of plants with their environment.These include pigments,volatiles,and defense compounds,some of which have applications in industry and agriculture.For example,isoprenoid drugs are used against cancer (taxol) or malaria (artemisin).But plants also synthesize isoprenoids with essential (primary) functions in respiration (ubiquinone),photosynthesis (carotenoids,chlorophylls,tocopherols,phylIoquinones,plastoquinone),membrane architecture (sterols),and growth regulation (brassinosteroids,cytokinins,gibberellins,abscisic acid,strigolactones).Despite their economic importance and biological relevance,our knowledge of the core pathways for the production of the universal isoprenoid precursors IPP and DMAPP in plant cells remained incomplete until the mid-1990s.Impressive progress in the last decade has resulted in the complete elucidation of several isoprenoid pathways,the identification of regulatory mechanisms,the discovery of new functions and properties of specific isoprenoids,and the successful manipulation of isoprenoid biosynthesis in a number of metabolic engineering approaches.In this update article,we will discuss some of the most recent advances in the plant isoprenoid field,focusing on the pathways supplying the C5 precursors in plant cells and the novel insights into regulatory matters. | Pablo Pulido Catalina Perello Manuel Rodriguez-Concepcion | 2012 | Molecular Plant2012，5，5： | 22 |
| 12 | Phytochrome Signaling in Green Arabidopsis Seedlings: Impact Assessment of a Mutually Negative phyB-PIF Feedback Loop显示文摘reversibly 红的(R)/far-red (FR )-light-responsive phytochrome (phy ) photosensory 系统在第一暴露之上在发芽黑暗的幼苗开始 deetiolation 进程到光,和阴影回避过程在充分,在到 vegetational 的暴露之上的 deetiolated 幼苗遮。到驾驶这些回答的 transcriptional 网络的从激活光的光敏电阻器 conformer (Pfr ) 的细胞内部的发信号小径与 bHLH 抄写因素的一个小亚科包含 Pfr 的直接、物理相互作用,称为的交往 Phy 因素(程序信息文件) ,它导致快速的程序信息文件解朊的降级。另外,有在光成年的幼苗的进一步的复杂性的证据, phyBPIF 相互作用由此相互地导致 phyB 降级,在里面一互相否定,反馈环配置。这里,在光成年的幼苗估计这些对抗活动的相对贡献到网 phenotypic 读出,我们检验了 light-shade-induced 的大小和 pentuple phyBpif1pif3pif4pif5 (phyBpifq ) 的 simulated-shade-induced 回答变异、各种各样的多重 pif 变异的联合。数据( 1 )重申 phyB 是占优势不独占,响应延长连续 R 照耀在 deetiolating 幼苗强加胚轴延伸的抑制的光敏电阻器并且( 2 )出现 PIF 四重唱( PIF1 , PIF3 , PIF4 ,并且 PIF5 )保留并且施加一个双能力在这些条件下面调制胚轴延伸由附随地通过内在的transcriptional规章的活动支持房间延伸,并且通过 feedb 减少phyB禁止的能力在暴露阴影的幼苗, immunoblot 分析证明在 Pfr 层次的强加阴影的减小在许多 PIF3 导致增加,并且变异的分析显示 PIF3 行动,到,与 PIF4 和 PIF5 一起支持胚轴延伸的已知的导致阴影的加速。相反地,尽管四倍的 pifq 异种显示清楚地减少了胚轴延伸与相比响应延长色泽野类型, immunoblot 分析不在变异的幼苗在 phyB 层次检测举起与相比在导致阴影的生长时期的多数期间野类型,并且 phyB 层次要用体力地没越过比较的pif变异的联合与生长显型被相关。这些结果建议 phyB 丰富的程序信息文件反馈调整不在在这些下面的支持程序信息文件的、阴影应答的显型的大小调节的 modulating 起一个主导的作用。在成长在下面的幼苗日报 lightdark 周期,在黑暗经期(End-of-Day-FR (EOD-FR ) 治疗) 的开始的 Pfr 的 FR-pulse-induced 移动相对没有 EOD-FR 治疗导致更长的胚轴并且这效果在 pif 变异的联合被稀释的数据表演测试了。这结果同样显示 PIF 四重唱成员能够内在地在光成年的植物支持胚轴房间延伸,独立于 photoactivated-phyB 丰富的程序信息文件反馈调整的效果。 | Pablo Leivar Elena Monte Megan M. Cohn Peter H. Quail | 2012 | Molecular Plant2012，5，3： | 20 |
| 13 | Alcoholic cardiomyopathy显示文摘Alcohol is the most frequently consumed toxic substance in the world. Low to moderate daily intake of alcohol has been shown to have beneficial effects on the cardiovascular system. In contrast, exposure to high levels of alcohol for a long period could lead to progressive cardiac dysfunction and heart failure. Cardiac dysfunction associated with chronic and excessive alcohol intake is a specific cardiac disease known as alcoholic cardiomyopathy(ACM). In spite of its clinical importance, data on ACM and how alcohol damages the heart are limited. In this review, we evaluate available evidence linking excessive alcohol consumption with heart failure and dilated cardiomyopathy. Additionally, we discuss the clinical presentation, prognosis and treatment of ACM. | Gonzalo Guzzo-Merello Marta Cobo-Marcos Maria Gallego-Delgado Pablo Garcia-Pavia | 2014 | World Journal of Cardiology2014，6，8： | 19 |
| 14 | 免疫鸡产生IgY抗体的技术显示文摘IgY技术正在成为生物技术领域和医药研究中的新热点 ,并且越来越得到国内同仁的重视。因为卵黄抗体 (IgY)化学性质稳定 ,产量高、成本低 ,以及动物种系距离的优势 ,更适于生产特异性抗体 ,具有开发功能性食品和新药的潜能。作为系列介绍的第二部分 ,本文详细介绍和探讨免疫鸡产生IgY抗体技术的主要技术环节和实践应用方面的具体信息 ,包括动物饲养 ,对鸡的免疫 ,抗体特性 ,IgY提取技术 ,鸡单克隆抗体的制备等方面。 | 张小莺 郑礼 Rüdiger Schade Horacio Raul Terzolo Hanibal Pablo Chacana Joanna Porankiewicz-Asplund | 2004 | 中国药理学通报2004，20，10： | 19 |
| 15 | 离子通道、磷酸化和哺乳动物精子获能显示文摘有性生殖动物需要精子和卵子之间进行精心协调的交流才能产生新的个体。精子获能是发生在女性生殖系统中的生殖细胞成熟的一个复杂现象,让精子能够和卵子联结并融合,是哺乳动物生育的必要条件。精子获能过程包括了质膜重组、离子渗透调节、胆固醇减少和许多蛋白质磷酸化状态的变化。研究精子离子通道的新工具能用更好的时空解析度将细胞内的离子变化和蛋白图像化,这些工具正在一步步阐明离子运输和磷酸化状态中的一系列调节是如何引起获能的。最近的证据表明有两条平行的通路调节引起获能的磷酸化发生。其中一条通路要求蛋白激酶A活化,另一条通路需要丝氨酸/苏氨酸磷酸酶失活。本文综述了精子获能所要求的离子运输参与和磷酸化信号处理。理解导致生育的分子机制,对于人们应对男性不育率升高、开发安全的以雄性配子为基础的避孕药、通过辅助生殖策略保持生物多样性都至关重要。 | Pablo E Visconti Dario Krapf Jose Luis de la Vega-Beltran Juan Jose Acevedo Alberto Darszon | 2011 | Asian Journal of Andrology2011，13，3： | 19 |
| 16 | La、Co取代对M型锶铁氧体结构和磁性能的影响显示文摘采用陶瓷法制备了La、Co取代的M型锶铁氧体Sr1-xLaxFe12-xCoxO19(x=0.05~0.20)。用X射线衍射仪、振动样品磁强计和永磁材料测量仪对粉末样品的结构与磁学性能进行了观测。系统地研究了La、Co取代对M型锶铁氧体结构和磁性能的影响。实验结果表明,随着替代量x的增大,内禀矫顽力Hcj增大,而比饱和磁化强度δs和剩磁Br先增大后减小。La、Co部分取代能明显改善M型锶铁氧体的内禀磁性。 | 黄凯 刘先松 周圣强 王勇 蔡霞 孙红军 马宝 Pablo Hernández-Gómez | 2006 | 磁性材料及器件2006，37，4： | 18 |
| 17 | Liver transplantation for hilar cholangiocarcinoma显示文摘The most appropriate treatment for Klatskin tumor(KT)with a curative intention is multimodal therapy based on achieving resection with tumour-free margins(R0resections)combined with other types of neoadjuvant or adjuvant treatment(the most important factor affecting KT survival is the possibility of R0 resections,achieving 5-year survival rate of 40%-50%).Thirty to forty percent of patients with KT are inoperable and present a 5-year survival rate of 0%.In irresectable non-disseminated KT patients,using liver transplantation without neoadjuvant treatment,the 5-year survival rate increase to 38%,reaching 50%survival in early stage.In selected cases,with liver transplantation and neoadjuvant treatment(chemotherapy and radiotherapy),the actuarial survival rate is 65%at 5 years and 59%at 10 years.In conclusion,correct staging,neoadjuvant treatment,living donor and priority on the liver transplant waiting list may lead to improved results. | Ricardo Robles Francisco Sánchez-Bueno Pablo Ramírez Roberto Brusadin Pascual Parrilla | 2013 | World Journal of Gastroenterology2013，19，48： | 17 |
| 18 | Phylogenetic alpha and beta diversity in tropical tree assemblages along regionalscale environmental gradients in northwest South America显示文摘Aims Environmental gradients are drivers of species diversity;however,we know relatively little about the evolutionary processes underlying these relationships.A potentially powerful approach to studying diversity gradients is to quantify the phylogenetic structure within and between assemblages arrayed along broad spatial and environmental gradients.Here,we evaluate the phylogenetic structure of plant assemblages along an environmental gradient with the expectation that the habitat specialization of entire lineages is an important evolutionary pattern influencing the structure of tree communities along environmental gradients.Methods We evaluated the effect of several environmental variables on the phylogenetic structure of plant assemblages in 145 plots distributed in northwestern South America that cover a broad environmental gradient.The phylogenetic alpha diversity was quantified for each plot and the phylogenetic beta diversity between each pair of plots was also quantified.Both the alpha and beta diversity measures were then related to spatial and environmental gradients in the study system.Important Findings We found that gradients in temperature and potential evapotranspiration have a strong relationship with the phylogenetic alpha diversity in our study system,with phylogenetic overdispersion in low temperatures and phylogenetic clustering at higher temperatures.Further,the phylogenetic beta diversity between two plots increases with an increasing difference in temperature,whereas annual precipitation was not a significant predictor of community phylogenetic turnover.We also found that the phylogenetic structure of the plots in our study system was related to the degree of seasonal flooding and seasonality in precipitation.In particular,more stressful environments such as dry forests and flooded forests showed phylogenetic clustering.Finally,in contrast with previous studies,we find that phylogenetic beta diversity was not strongly related to the spatial distance separating two forest plots,which may be the result of the importance of the three independent mountain ranges in our study system,which generate a high degree of environmental variation over very short distances.In conclusion,we found that environmental gradients are important drivers of both phylogenetic alpha and phylogenetic beta diversities in these forests over spatial distance. | Sebastián González-Caro María Natalia Umaña Esteban Álvarez Pablo R.Stevenson Nathan G.Swenson | 2014 | Journal of Plant Ecology2014，7，2： | 17 |
| 19 | The Immune System and the Role of Inflammation in Perinatal Depression显示文摘Major depression during pregnancy is a common psychiatric disorder that arises from a complex and multifactorial etiology. Psychosocial stress, sex, hormones, and genetic vulnerability increase the risk for triggering mood disorders. Microglia and toll-like receptor 4 play a crucial role in triggering wide and varied stress-induced responses mediated through activation of the inflammasome; this leads to the secretion of inflammatory cytokines, increased serotonin metabolism, and reduction of neurotransmitter availability along with hypothalamic–pituitary–adrenal axis hyperactivity. Dysregulation of this intricate neuroimmune communication network during pregnancy modifies the maternal milieu, enhancing the emergence of depressive symptoms and negative obstetric and neuropsychiatric outcomes. Although several studies have clearly demonstrated the role of the innate immune system in major depression, it is still unclear how the placenta, the brain, and the monoaminergic and neuroendocrine systems interact during perinatal depression. Thus, in the present review we describe the cellular and molecular interactions between these systems in major depression during pregnancy, proposing that the same stress-related mechanisms involved in the activation of the NLRP3 inflammasome in microglia and peripheral myeloid cells in depressed patients operate in a similar fashion in the neuroimmune placenta during perinatal depression. Thus, activation of Toll-like receptor 2 and 4 signaling and the NLRP3 inflammasome in placental immune cells may promote a shift of the Th1/Th2 bias towards a predominant Th1/Th17 inflammatory response, associated with increased secretion of pro-inflammatory cytokines, among other secreted autocrine and paracrine mediators, which play a crucial role in triggering and/or exacerbating depressive symptoms during pregnancy. | Philippe Leff-Gelman Ismael Mancilla-Herrera Monica Flores-Ramos Carlos Cruz-Fuentes Juan Pablo Reyes-Grajeda maría del pilar garcía-cuétara Marielle Danitza Bugnot-Perez David Ellioth Pulido-Ascencio | 2016 | Neuroscience Bulletin2016，32，4： | 17 |
| 20 | Hepatic encephalopathy:An approach to its multiple pathophysiological features显示文摘Hepatic encephalopathy(HE)is a neuropsychiatric complex syndrome,ranging from subtle behavioral abnormalities to deep coma and death.Hepatic encephalopathy emerges as the major complication of acute or chronic liver failure.Multiplicity of factors are involved in its pathophysiology,such as central and neuromuscular neurotransmission disorder,alterations in sleep patterns and cognition,changes in energy metabolism leading to cell injury,an oxidative/nitrosative state and a neuroinflammatory condition.Moreover,in acute HE,a condition of imminent threat of death is present due to a deleterious astrocyte swelling.In chronic HE,changes in calcium signaling,mitochondrial membrane potential and long term potential expression,N-methyl-D-aspartate-cGMP and peripheral benzodiazepine receptors alterations,and changes in the mRNA and protein expression and redistribution in the cerebral blood flow can be observed.The main molecule indicated as responsible for all these changes in HE is ammonia.There is no doubt that ammonia,a neurotoxic molecule,triggers or at least facilitates most of these changes.Ammonia plasma levels are increased two-to three-fold in patients with mild to moderate cirrhotic HE and up to ten-fold in patients with acute liver failure. Hepatic and inter-organ trafficking of ammonia and its metabolite,glutamine(GLN),lead to hyperammonemic conditions.Removal of hepatic ammonia is a differentiated work that includes the hepatocyte,through the urea cycle,converting ammonia into GLN via glutamine synthetase.Under pathological conditions,such as liver damage or liver blood bypass,the ammonia plasma level starts to rise and the risk of HE developing is high. Knowledge of the pathophysiology of HE is rapidly expanding and identification of focally localized triggers has led the development of new possibilities for HE to be considered.This editorial will focus on issues where, to the best of our knowledge,more research is needed in order to clarify,at least partially,controversial topics. | Juan Carlos Perazzo Silvina Tallis Amalia Delfante Pablo Andrés Souto Abraham Lemberg Francisco Xavier Eizayaga Salvador Romay | 2012 | World Journal of Hepatology2012，4，3： | 16 |
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