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| 1 | Biochemical mechanisms in drug-induced liver injury:Certainties and doubts显示文摘Drug-induced liver injury is a significant and still unresolved clinical problem.Limitations to knowledge about the mechanisms of toxicity render incomplete the detection of hepatotoxic potential during preclinical development.Several xenobiotics are lipophilic substances and their transformation into hydrophilic compounds by the cytochrome P-450 system results in production of toxic metabolites.Aging,preexisting liver disease,enzyme induction or inhibition,genetic variances,local O2 supply and,above all,the intrinsic molecular properties of the drug may affect this process.Necrotic death follows antioxidant consumption and oxidation of intracellular proteins,which determine increased permeability of mitochondrial membranes,loss of potential,decreased ATP synthesis,inhibition of Ca2+-dependent ATPase,reduced capability to sequester Ca2+ within mitochondria,and membrane bleb formation.Conversely,activation of nucleases and energetic participation of mitochondria are the main intracellular mechanisms that lead to apoptosis.Non-parenchymal hepatic cells are inducers of hepatocellular injury and targets for damage.Activation of the immune system promotes idiosyncratic reactions that result in hepatic necrosis or cholestasis,in which different HLA genotypes might play a major role.This review focuses on current knowledge of the mechanisms of drug-induced liver injury and recent advances on newly discovered mechanisms of liver damage.Future perspectives including new frontiers for research are discussed. | Ignazio Grattagliano Leonilde Bonfrate Catia V Diogo Helen H Wang David QH Wang Piero Portincasa | 2009 | World Journal of Gastroenterology2009，15，39： | 30 |
| 2 | 2018加拿大心境障碍与焦虑障碍治疗协作组/国际双相障碍学会指南:双相障碍的管理显示文摘加拿大心境障碍与焦虑障碍治疗协作组(Canadian Network for Mood and Anxiety Treatments,CANMAT)曾于2005年发布了第1版双相障碍管理指南,并分别于2007、2009和2013年对该指南进行了更新,其中最近的2次更新是与国际双相障碍学会(International Society for Bipolar Disorders,ISBD)合作完成。2018版CANMAT/ISBD双相障碍治疗指南(以下简称指南)反映了自2005年首版指南发表以来本领域取得的重大进展,包括疾病诊断与疾病管理的更新以及药物治疗与心理治疗的近期研究进展。这些前沿进展中综合考虑了循证证据的级别,并基于治疗疗效、临床实践经验、安全性、耐受性和药物导致的转相风险等,对一线、二线及三线治疗方案进行了简明而清晰的推荐。本指南中新增内容涵盖了双相Ⅰ型障碍(BD-Ⅰ)的躁狂发作急性期、抑郁发作急性期和双相障碍维持期的一线及二线治疗推荐等级划分。这种对治疗推荐等级的划分综合考虑了治疗方法对双相障碍不同时相的影响,将进一步帮助临床医生做出基于循证证据的治疗决策。锂盐、喹硫平、双丙戊酸盐、阿塞那平、阿立哌唑、帕利哌酮、利培酮和卡利拉嗪单药或联合使用被推荐为躁狂发作急性期的一线治疗选择。BD-Ⅰ抑郁期的一线治疗选择包括喹硫平、鲁拉西酮、锂盐、拉莫三嗪单药,鲁拉西酮联合锂盐或双丙戊酸盐或拉莫三嗪辅助治疗。尽管急性期治疗有效的药物通常应继续用于BD-Ⅰ的维持期治疗,但也存在一些特殊情况(例如抗抑郁药)。现有数据表明,锂盐、喹硫平、双丙戊酸盐、拉莫三嗪、阿塞那平和阿立哌唑单药或联合治疗应被视为维持治疗的初始或更换治疗方案时的一线选择。除了探讨BD-Ⅰ的相关问题外,本指南中还对双相Ⅱ型障碍(BD-Ⅱ)的临床管理进行了系统回顾并给予治疗推荐,同时针对特殊人群也有相关推荐,如处于各个生殖周期的女性、儿童、青少年和老年人。此外,本指南中还讨论了特定精神疾病及共病(如物质滥用、焦虑障碍和代谢性疾病)的影响。最后,本指南中概述了安全性和药物监测的相关问题。CANMAT/ISBD工作组希望本指南能够成为全球临床医生的实用工具。 | Lakshmi N Yatham Sidney H Kennedy Sagar V Parikh Ayal Sehaffer David J Bond Benicio N Frey Verinder Sharma Benjamin I Goldstein Soham Rej Serge Beaulieu Martin Alda Glenda MaeQueen Roumen V Milev Arun Ravindran Claire O'Donovan Diane Mclntosh Raymond W Lam Gustavo Vazquez Flavio Kapczinski Roger S Melntyre Jan Kozicky Shigenobu Kanba Beny Lafer Trisha Suppes Joseph R Calabrese Eduard Vieta Gin Malhi Robert M Post Michael Berk 胡晨(译) 王刚(译) | 2019 | 中华精神科杂志2019，52，1： | 25 |
| 3 | 具有低动脉粥样硬化风险特征的专业耐力运动员的亚临床冠状动脉疾病发病率显示文摘研究表明,具有冠状动脉疾病(coronary artery disease,CAD)危险因素的中老年(健将)运动员比久坐个体冠状动脉钙化(coronary artery calcium,CAC)评分更高。尚没有研究评估具有低动脉粥样硬化风险特征的专业运动员的CAD患病率。 | 刘莉 叶鹏 Merghani A Maestrini V Rosmini S Cox AT Dhutia H Bastiaenen R David S Yeo TJ Narain R Malhotra A Papadakis M Wilson MG Tome M AlFakih K Moon JC Sharma S | 2017 | 中华高血压杂志2017，25，6： | 8 |
| 4 | 钠-葡萄糖共转运蛋白-2抑制剂或胰高血糖素样肽-1受体激动剂治疗成人2型糖尿病:临床实践指南显示文摘临床问题对于存在不同心血管风险及肾脏结局的2型糖尿病患者,在原有生活方式干预和/或其他降糖药物的基础上加用钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂的获益及风险是什么?现行做法几十年来,2型糖尿病的治疗决策都以控制血糖为主导。SGLT-2抑制剂和GLP-1受体激动剂在传统观念中常被用于二甲双胍治疗后血糖仍控制不佳的患者。目前这一现状已经发生了改变,这得益于多项临床研究结果。研究显示SGLT-2抑制剂和GLP-1受体激动剂拥有独立于药物降糖作用之外的对于动脉粥样硬化性心血管病(CVD)和慢性肾脏病(CKD)的获益。建议本指南阐述了针对不同风险分层的成人2型糖尿病患者使用SGLT-2抑制剂或GLP-1受体激动剂的建议。•伴有3种或更少的心血管风险因素且不存在CVD或CKD:不建议启动SGLT-2抑制剂或GLP-1受体激动剂治疗。(推荐等级:弱)•伴有3种以上心血管风险因素且不存在CVD或CKD:建议启动SGLT-2抑制剂治疗,不建议启动GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD或CKD:建议启动SGLT-2抑制剂治疗和GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD和CKD:建议启动SGLT-2抑制剂治疗(推荐等级:强)和GLP-1受体激动剂治疗。(推荐等级:弱)•对于那些想要进一步降低CVD和CKD结局风险的患者:推荐优先启用SGLT-2抑制剂治疗而非GLP-1受体激动剂治疗。(推荐等级:弱)这项指南是如何制订的一个由患者、临床医生和方法学家共同组成的国际小组提出了这些推荐意见。这些推荐意见基于可信度较高的指南的标准,并使用GRADE分级方法进行评估。该小组采用了息者个体化的观点。证据一项关于获益与风险的系统综述和网络meta分析(764项随机对照研究,包括421346例参与者)发现SGLT-2抑制剂和GLP-1受体激动剂可以降低总体死亡率、心肌梗死发生率、终末期肾病或肾衰竭的发生率(中等至高等质量的证据)。在不同的亚组中这些药物对卒中、因心力衰竭所致住院和其他主要不良事件有不同的影响。药物绝对获益的程度因患者个体风险的不同有很大的差异。(例如,对于接受了超过5年药物治疗的1000例患者,在最低风险人群中死亡人数减少了5人,在最高风险人群中死亡人数减少了48人)。一项关于预后的综述确认了14种风险预测模型,其中一种(RECODe)在证据总结中报告了大部分基线风险评估数据,小组利用该模型以支持风险分层的建议。考虑到患者的价值观及个体差异,指南推荐的支撑证据包括一项对已发表论文的系统综述、一项患者焦点小组研究、一项临床问题总结,以及一项指南调查。指南解读我们依据不同的CVD和CKD风险水平,综合考虑获益、风险和其他因素的平衡,以及每一个风险组别的实际问题,来对推荐意见进行分层。本指南强烈建议CVD和CKD患者使用SGLT-2抑制剂治疗,这说明专家组认为其具有显著的获益。而对于其他成人2型糖尿病患者,推荐等级较弱,这说明专家组想要在获益、风险及治疗花费上取得一个更好的平衡。临床医生通过该指南可以使用可靠的风险计算模型,如RECODe,来明确其患者的个体心血管和肾脏疾病风险。医患交互式总结临床证据和制订决策有助于患者知晓治疗选择,包括进行共同决策。2型糖尿病人群(全球患病率不断增长1-2)正面临着不断增加的心血管疾病、肾脏病和其他并发症的风险3。数十年来,2型糖尿病的管理始终以控制血糖及糖化血红蛋白(HbA1c)为治疗目标4-5,但是,最近的高质量随机对照研究已经对这种以血糖为中心的治疗模式发起了挑战。研究结果显示,强化血糖控制未必会降低大血管不良事件,它还可能带来不利影响监管机构现在要求新型糖尿病药物必须证明其具有心血管和肾脏获益才能获得批准。对两类新药--钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂(见框图1)的临床试验结果显示,在现有治疗方案(常规治疗)之上加用这些药物,对死亡、心肌梗死、卒中、心力衰竭和肾脏的结局(如进展为终末期肾病)都有获益8-12。 | Sheyu Li Per Olav Vandvik Lyubov Lytvyn Gordon H Guyatt Suetonia C Palmer Rene Rodriguez-Gutierrez Farid Foroutan Thomas Agoritsas Reed A C Siemieniuk Michael Walsh Lawrie Frere David J Tunnicliffe Evi V Nagler Veena Manja Bjφrn Olav Asvold Vivekanand Jha Mieke Vermandere Karim Gariani Qian Zhao Yan Ren Emma Jane Cartwright Patrick Gee Alan Wickes Linda Fems Robin Wright Ling Li Qiukui Hao Reem A Mustafa 无 郭鹤鸣(译) | 2021 | 英国医学杂志中文版2021，24，9： | 7 |
| 5 | Approach to medical therapy in perianal Crohn’s disease显示文摘Perianal Crohn’s disease remains a challenging condition to treat and can have a substantial negative impact on quality of life.It often requires combined surgical and medical interventions.Anti-tumor necrosis factor(anti-TNF)therapy,including infliximab and adalimumab,remain preferred medical therapies for perianal Crohn’s disease.Infliximab has been shown to be efficacious in improving fistula closure rates in randomized controlled trials.Clinicians can be faced with a number of questions relating to the optimal use of anti-TNF therapy in perianal Crohn’s disease.Specific issues include evaluation for the presence of perianal sepsis,the treatment target of therapy,the ideal time to commence treatment,whether additional medical therapy should be used in conjunction with anti-TNF therapy,and the duration of treatment.This article will discuss key studies which can assist clinicians in addressing these matters when they are considering or have already commenced anti-TNF therapy for the treatment of perianal Crohn’s disease.It will also discuss current evidence regarding the use of vedolizumab and ustekinumab in patients who are failing to achieve a response to anti-TNF therapy for perianal Crohn’s disease.Lastly,new therapies such as local injection of mesenchymal stem cell therapy will be discussed. | Abhinav Vasudevan David H Bruining Edward V Loftus Jr William Faubion Eric C Ehman Laura Raffals | 2021 | World Journal of Gastroenterology2021，27，25： | 4 |
| 6 | Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial显示文摘 | Kris V Kowdley Eric Lawitz Israel Crespo Tarek Hassanein Mitchell N Davis Michael DeMicco David E Bernstein Nezam Afdhal John M Vierling Stuart C Gordon Jane K Anderson Robert H Hyland Hadas Dvory-Sobol Di An Robert G Hindes Efsevia Albanis William T Symo | 2013 | The Lancet2013，，9883： | 3 |
| 7 | Axial strain enhances osteotomy repair with a concomitant increase in connexin43 expression显示文摘The mechanical environment is known to influence fracture healing. We speculated that connexin43(Cx43) gap junctions, which impact skeletal homeostasis, fracture healing and the osteogenic response to mechanical load,may play a role in mediating the response of the healing bone to mechanical strain. Here, we used an established rat fracture model, which uses a 2 mm osteotomy gap stabilized by an external fixator, to examine the impact of various cyclical axial loading protocols(2%, 10%, and 30% strain) on osteotomy healing. We examined the presence of Cx43 in the osteotomy-healing environment and assessed how mechanical strain modulates Cx43 expression patterns in the callus. We demonstrated that increased cyclical axial strain results in increased radiographic and histologic bone formation. In addition, we show by immunohistochemistry that Cx43 is abundantly expressed in the healing callus, with the expression most robust in samples exposed to increased cyclical axial strain. These data are consistent with the concept that an increase in Cx43 expression by mechanical load may be part of the mechanisms by which mechanical forces enhances fracture healing. | Rishi R Gupta Hyunchul Kim Yu-Kwan Chan Carla Hebert Leah Gitajn David J Yoo Robert V O’Toole Adam H Hsieh Joseph P Stains | 2015 | Bone Research2015，3，2： | 2 |
| 8 | Frostfire:An experimental approach to predicting the climate feedbacks from the changing boreal fire regime显示文摘 | Larry D H Masami F David V S | 2003 | Journal of Geophysical Research2003，108，： | 1 |
| 9 | Late Glacial temperature and precipitation changes in tile lowland Neotropics by tandem measurement of lSO in biogenic carbonate and gypsum hydration water显示文摘 | DAVID A H ALEXANDRA V T CAMILLA J W | 2012 | Geochimica et Cosmochimica Acta2012，77，： | 1 |
| 10 | The TNF receptor 1-associated prorein TRADD signals cell death and NF-B activation显示文摘 | Hsu H Xiong J David V | 1995 | Cell1995，81，： | 1 |
| 11 | Mechanical loading down-regulates peroxisome proliferator activated receptor gamma in bone marrow stromal cells and fa vors osteoblastogenesis at the expense of adipogenesis显示文摘 | DAVID V MARTIN A LAFAGE-PROUST M H | 2007 | Endocrinology2007，148，5： | 1 |
| 12 | Spider and mulberry silkworm silks as compatible biomaterials 显示文摘 | Osnat H David PK Fritz V | 2007 | Compos B Eng2007，38，3： | 1 |
| 13 | The NIH human microbiome project显示文摘 | NIH HMP Working Group Peterson J Garges S Giovanni M McInnes P Wang L Schloss JA Bonazzi V McEwen JE Wetterstrand KA Deal C Baker CC Di Francesco V Howcroft TK Karp RW Lunsford RD Wellington CR Belachew T Wright M Giblin C David H Mills M Salomon R Mullins C Akolkar B Begg L Davis C Grandison L Humble M Khalsa J Little AR Peavy H Pontzer C Portnoy M Sayre MH Starke-Reed P Zakhari S Read J Watson B Guyer M | 2009 | Genome Res2009，19，12： | 1 |
| 14 | Training a neural-network based intrusion detector to recognize novel attacks显示文摘 | Susan C L David V H | 2001 | IEEE Transactions on systems man and cybernetics-part a:System and Humans2001，31，： | 1 |
| 15 | Pharmacological activities of natural triterpenoids and their therapeutic implications显示文摘 | PETR D MARIAN H DAVID V | 2006 | J Nat Prod2006，23，3： | 1 |
| 16 | Over-expression of the DMP1 C-terminal fragment stimulates FGF23 and exacerbates the hypophosphatemic rickets phenotype in Hyp mice显示文摘 | Martin A David V Li H Dai B Feng JQ Quarles LD | | 0，，： | 1 |
| 17 | Process- ing intermetallic composites by self propagating, high-tempera- ture synthesis 显示文摘 | DAVID E A JEFFREY A H ARTHUR V P | 1994 | Journal of Metals1994，46，1： | 1 |
| 18 | Mechanical loading down-regulates peroxisome proliferator- activated receptor gamma in bone marrow stromal cells and favors osteoblastogenesis at the expense of adipogenesis 显示文摘 | DAVID V MARTIN A LAFAGE-PROUST M H | 2007 | Endocrinology2007，148，5： | 1 |
| 19 | Property rights and sustainable nature tourism: adaptation and mal- adaptation in Dalarna (Sweden) and Maine (USA) 显示文摘 | David V Lars H | 2000 | Ecological Economics2000，35，： | 1 |
| 20 | Effect of Magnetic Hysteresis on Rotational Losses in Heteropolar Magnetic Bearings显示文摘 | David C Meeker Alexei V Filatov and Eric H | 2004 | IEEE Transactions on Magnetics2004，40，5： | 1 |
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