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| 1 | INT-767 improves histopathological features in a dietinduced ob/ob mouse model of biopsy-confirmed nonalcoholic steatohepatitis显示文摘AIM To characterize the efficacy of the dual FXR/TGR5 receptor agonist INT-767 upon histological endpoints in a rodent model of diet-induced and biopsy-confirmed non-alcoholic steatohepatitis(NASH).METHODS The effects of INT-767 on histological features of NASH were assessed in two studies using Lep^(ob/ob)(ob/ob) NASH mice fed the AMLN diet(high fat with transfat, cholesterol and fructose). In a proof-of-conceptstudy, Lep^(ob/ob)(ob/ob) NASH mice were first dosed with INT-767(3 or 10 mg/kg for 8 wk). A second ob/ob NASH study compared INT-767(3 and 10 mg/kg) to obeticholic acid(OCA)(10 or 30 mg/kg; 16 wk). Primary histological endpoints included qualitative and quantitative assessments of NASH. Other metabolic and plasma endpoints were also assessed. A comparative assessment of INT-767 and OCA effects on drug distribution and hepatic gene expression was performed in C57 Bl/6 mice on standard chow. C57 Bl/6 mice were orally dosed with INT-767 or OCA(1-30 mg/kg) for 2 wk, and expression levels of candidate genes were assessed by RNA sequencing and tissue drug levels were measured by liquid chromatography tandem-mass spectrometry.RESULTS INT-767 dose-dependently(3 and 10 mg/kg, PO, QD, 8 wk) improved qualitative morphometric scores on steatohepatitis severity, inflammatory infiltrates and fibrosis stage. Quantitative morphometric analyses revealed that INT-767 reduced parenchymal collagen area, collagen fiber density, inflammation(assessed by Galectin-3 immunohistochemistry) and hepatocyte lipid droplet area following INT-767 treatment. In a comparative study(16 wk), the FXR agonists OCA(10 and 30 mg/kg) and INT-767(3 and 10 mg/kg) both improved NASH histopathology, with INT-767 exerting greater therapeutic potency and efficacy than OCA. Mechanistic studies suggest that both drugs accumulate similarly within the liver and ileum, however, the effects of INT-767 may be driven by enhanced hepatic, but not ileal, FXR function. CONCLUSION These findings confirm the potential utility of FXR and dual FXR/TGR5 activation as disease intervention strategies in NASH. | Jonathan D Roth Michael Feigh Sanne S Veidal Louise KD Fensholdt Kristoffer T Rigbolt Henrik H Hansen Li C Chen Mathieu Petitjean Weslyn Friley Niels Vrang Jacob Jelsing Mark Young | 2018 | World Journal of Gastroenterology2018，24，2： | 7 |
| 2 | Targeting ryanodine receptors for anti-arrhythmic therapy显示文摘Antiarrhythmic 药是压制或阻止反常的心节奏的一组药品,它经常与实质的病态和死亡被联系。典型地指向血浆膜离子隧道的当前的 antiarrhythmic 药限制了临床的成功,在一些,情况被描述了为是支持 arrhythmic。然而,最近的研究建议钙的那个病理学的版本(从经由心脏的 ryanodine 受体(RyR2 ) 的 sarcoplasmic 蜂窝胃的 Ca 2+) 能为 antiarrhythmic 代表一个有希望的目标治疗。心脏舒张的 SR Ca 2+ 版本在两个被连接了到 arrhythmogenesis 继承心律不齐症候群“ catecholaminergic 多态的室的心悸亢进”并且心疾病的获得的形式(例如, atrial 纤维性颤动,心失败) 。药品的几个班被显示了减少反常 RyR2 活动并且可以通过 SR Ca 2+ 漏缝的减小对触发的心律不齐授与保护。在这评论,我们将为稳定 RyR2 评估当前的药理学方法并且基于分子的机制的当前的证据建议处理形式。 | Mark D McCAULEY | 2011 | Acta Pharmacologica Sinica2011，32，6： | 3 |
| 3 | 跨音速转子叶顶泄漏流/主流交界面的前移机制显示文摘采用数值计算和实验研究相结合的方法,研究了跨音速转子叶顶泄漏流与主流交界面轴向位置随流量的变化规律和机制。该跨音转子是美国圣母大学一级半跨音速压气机转子。研究发现机匣壁面脉线分布能够定性反映壁面轴向剪切应力分布,可用来识别叶顶泄漏流与主流的交界面位置。通过机匣壁面的脉线分布,可以看出机匣壁面存在两条零剪切应力线。第一条零剪切应力线表示来流与叶顶泄漏流之间交界面的时间和周向平均轴向位置,在小流量工况下交界面靠近顶部叶片的前缘。计算和实验结果都表明,随着质量流量的减小,叶顶泄漏流与主流交界面的轴向位置不断向叶片前缘移动。在近失速点,交界面到达叶片前缘,泄漏流即将溢出。泄漏流与主流的轴向动量比随流量减小不断增大的变化规律进一步说明,间隙区域泄漏流与主流的轴向动量平衡是导致交界面不断前移直至溢出的内在机制。 | 杜娟 林峰 陈静宜 Mark H Ross Joshua D Cameron Scott C Morris | 2011 | 工程热物理学报2011，32，6： | 3 |
| 4 | Dietary approaches following endoscopic retrograde cholangiopancreatography: A survey of selected endoscopists显示文摘AIM: To describe the dietary recommendations of experienced endoscopists for patients who have undergone endoscopic retrograde cholangiopancreatography (ERCP) and the factors that influence these recommendations. METHODS: Selected U.S. endoscopists with ERCP experience were surveyed by e-mail. A questionnaire with three hypothetical ERCP cases of patients at low, medium and high risk for development of post-ERCP pancreatitis (PEP) was shown. For each scenario, respondents were asked to recommend a post-procedure diet and time to first oral intake. Respondents were also asked about the effect of various clinical factors on their recommendations, including risk of PEP.RESULTS: 97/187 selected ASGE members (51.9%) responded. When risk of PEP was either low, medium or high, 53%, 88% and 96% recommended a diet of clear liquids/NPO respectively, and 2%, 5% and 18% recommended delaying first oral intake until the following day. About 88% of respondents gave the same type of diet to patients at high as those with moderate-risk of PEP (P = 0.04). However, 37% and 43% of respondents gave different types of diet to patients at low vs moderate-risk and low-risk vs high-risk of PEP respectively (P < 0.001). No statistically significant associations were found regarding the effect of other clinical factors or respondent demographics.CONCLUSION: Most experienced endoscopists limit diet to NPO/clear liquids after ERCP for patients at high or moderate risk of post-ERCP pancreatitis. About half allow a low-fat or regular diet in patients at low risk. | Lincoln EVVC Ferreira Mark D Topazian William S Harmsen Alan R Zinsmeister Todd H Baron | 2010 | World Journal of Gastrointestinal Endoscopy2010，2，12： | 3 |
| 5 | 抑郁症的非药物治疗:系统性综述与证据图显示文摘背景抑郁症非药物治疗的疗效比较目前仍然不清楚。方法我们对一些系统性综述作了概述,回顾了随机对照试验(RCT),比较抑郁症非药物治疗的有效性和认知行为治疗(CBT)。对多个电子数据库在2016年2月之前发表的所有文献进行了检索,不限制语言。成对的评阅人进行资料纳入、数据提炼并评估偏倚的风险。在适用的时候进行了荟萃分析。结果我们收录了367项RCT,纳入了约2000名患者,进行了11种治疗,导出17项独立的头对头比较。通过标准化的量表评估,发现CBT、自然疗法、行为干预与躯体活动干预可以降低抑郁的严重程度。然而,这些非药物干预的相对疗效仍然缺乏。这些干预对临床缓解和复发的效果不清楚。CBT的发生率比抗抑郁药物更低。局限性由于证据缺乏一致性、证据不清或偏倚风险高,导致证据的质量只是低到中等,限制了我们研究结果的可信度。结论抑郁症的非药物治疗能减少抑郁症状,在轻度到重度抑郁症患者中,应当合并抗抑郁药物治疗,一同进行。对于非药物治疗的选择,应当根据患者的价值观、偏好、临床和社会因素来与患者共同作出决定。 | Wigdan H Farah Mouaz Alsawas Maria Mainou Fares Alahdab Magdoleen H Farah Ahmed T Ahmed Essa A Mohamed Jehad Almasri Michael R Gionfriddo Ana Castaneda-Guarderas Khaled Mohammed Zhen Wang Noor Asi Craig N Sawchuk Mark D Williams Larry J Prokop M Hassan Murad Annie LeBlanc | 2017 | 英国医学杂志中文版2017，20，11： | 2 |
| 6 | GRADE:在推荐分级中体现对资源利用的考虑显示文摘指南小组成员对资源利用是否会影响个体患者的治疗决策有不同看法。由于医疗费用上涨,必须考虑资源利用的影响,但指南小组成员可能会发现这有很大的挑战性。 | Gordon H Guyatt Andrew D Oxman Regina Kunz Roman Jaeschke Mark Helfand Alessandro Liberati Gunn E Vist Holger J Schьnemann 王菊芬 陈耀龙 李幼平 | 2009 | 中国循证医学杂志2009，9，6： | 2 |
| 7 | Aflatoxin Exposure and Viral Hepatitis in the Etiology of Liver Cirrhosis in The Gambia, West Africa显示文摘 | Kuniholm Mark H Lesi Olufunmilayo A Mendy Maimuna Akano Aliu O Sam Omar Hall Andrew J Whittle Hilton Bah Ebrima Goedert James J Hainaut Pierre Kirk Gregory D | 2008 | Environmental Health Perspectives2008，，11： | 2 |
| 8 | Telangiectatic osteosarcoma:radiologic-pathologic comparison显示文摘 | Mark D M Suphanee wan Jaovisidha H Thomas T | 2003 | Radiology2003，229，： | 1 |
| 9 | Polybrominated diphenyl ether (PBDE) flame retardants显示文摘 | Frank Rahman Katherine H Langford Mark D Scrimshaw John N Lester | 2001 | Science of the Total Environment2001，，1： | 1 |
| 10 | Bacterial RNA chaperones confer abiotic stress tolerance in plants and improved grain yield in maize under water-limited condition 显示文摘 | Paolo C Dave W Robert J B Don C A Jay H Martin S Mark A Ganesh K Sara S Robert D Santiago N Stephanie B Mary F Jayaprakash T Santanu D Christopher B Michael H L Jacqueline E H | 2008 | Plant Physiology2008，147，2： | 1 |
| 11 | J Colloid InterfSci 显示文摘 | Mattson J S Mark H B Malbin M D | 1969 | 31(1): 1161969，31，1： | 1 |
| 12 | Ectomycurrhizae as Biological Deterrents to pathogenie root infections显示文摘 | Mark D H | 1971 | Mycorrhizae1971，，： | 1 |
| 13 | Catheter ablation for atrial fibrillation显示文摘 | Mark D O'Neill PJ Michel H | 2007 | Circulation2007，116，12： | 1 |
| 14 | Amino acid composition of leaf protein显示文摘 | Eldean D Gerloff Iracema H Lima Mark A Stahman | 1965 | Agriculture and Food Chemistry1965，13，2： | 1 |
| 15 | Membrane compliance and liquefaction of sluiced gravel specimens显示文摘 | Evans Mark D Seed H Bnlton Seed Raymond B | 1995 | Journal of Geotechnical Engineering1995，118，6： | 1 |
| 16 | Toroidal pores formed by antimicrobial peptides show significant disorder 显示文摘 | Sengupta D Leontiadou H Mark A E | 2008 | Biochim Biophys Acta2008，1778，10： | 1 |
| 17 | Amiodarone or an implant- able cardioverter-defibrillator for congestive heart failure 显示文摘 | Bardy G H Lee K L Mark D B | 2005 | N Engl J Med2005，352，3： | 1 |
| 18 | Health characteristics and behaviors of adults with mental retardation residing in three liv ing arrangements 显示文摘 | Rimmer J H Braddock D Marks B | 1995 | Research in developmental disabilities1995，16，6： | 1 |
| 19 | Prospective study of perceived stress in cardiac patients显示文摘 | Brummett B H Babyak M A Mark D B | 2004 | Ann Behav Med2004，27，1： | 1 |
| 20 | Challenges for land system science显示文摘 | MARK D A R BAS P KARL H E | 2012 | Land Use Policy2012，29，4： | 1 |
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