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| 1 | miRNAS in cardiovascular diseases: potential biomarkers, therapeutic targets and challenges显示文摘心血管的疾病(CVD ) 在世界上是病态和死亡的领先的原因。尽管可观的进步在 CVD 的诊断,治疗和预后被取得了,仍然有批评需要让新奇诊断 biomarkers 和新治疗学的干预减少这疾病的发生。最近,正在增加证据那传播 miRNAs (miRNAs ) ,即内长的、稳定的、搁浅单人赛的、短、非编码的 RNA,能为 CVD 被用作诊断 biomarkers。而且, miRNAs 为几心血管的混乱代表潜在的新奇治疗学的目标。在这评论我们提供几 CVD 的效果的概述;包括心失败,尖锐心肌的梗塞,心律不齐和肺的高血压;在传播 miRNAs 的层次上。另外, miRNA 的使用也作为治疗学的目标被讨论,以及质问并且在他们在 CVD 的诊断的使用的建议。 | Shan-shan ZHOU Jing-peng JIN Ji-qun WANG Zhi-guo ZHANG Jonathan H FREEDMAN Yang ZHENG Lu CAI | 2018 | Acta Pharmacologica Sinica2018，39，7： | 31 |
| 2 | Arrhythmogenic mechanisms in ryanodine receptor channelopathies显示文摘Ryanodine receptors(Ry Rs) are the calcium release channels of sarcoplasmic reticulum(SR) that provide the majority of calcium ions(Ca2+) necessary to induce contraction of cardiac and skeletal muscle cells.In their intracellular environment,Ry R channels are regulated by a variety of cytosolic and luminal factors so that their output signal(Ca2+) induces finely-graded cell contraction without igniting cellular processes that may lead to aberrant electrical activity(ventricular arrhythmias) or cellular remodeling.The importance of Ry R dysfunction has been recently highlighted with the demonstration that point mutations in RYR2,the gene encoding for the cardiac isoform of the Ry R(Ry R2),are associated with catecholaminergic polymorphic ventricular tachycardia(CPVT),an arrhythmogenic syndrome characterized by the development of adrenergically-mediated ventricular tachycardia in individuals with an apparently normal heart.Here we summarize the state of the field in regards to the main arrhythmogenic mechanisms triggered by Ry R2 channels harboring mutations linked to CPVT.Most CPVT mutations characterized to date endow Ry R2 channels with a gain of function,resulting in hyperactive channels that release Ca2+ spontaneously,especially during diastole.The spontaneous Ca2+ release is extruded by the electrogenic Na+/Ca2+ exchanger,which depolarizes the external membrane(delayed afterdepolarization or DAD) and may trigger untimely action potentials.However,a rare set of CPVT mutations yield Ry R2 channels that are intrinsically hypo-active and hypo-responsive to stimuli,and it is unclear whether these channels release Ca2+ spontaneously during diastole.We discuss novel cellular mechanisms that appear more suitable to explain ventricular arrhythmias due to Ry R2 loss-of-function mutations. | ZHAO Yan-Ting VALDIVIA Carmen R. GURROLA Georgina B. HERNNDEZ Jonathan J. VALDIVIA Héctor H. | 2015 | Science China(Life Sciences)2015，58，1： | 14 |
| 3 | Cardiotrophin 1 stimulates beneficial myogenic and vascular remodeling of the heart显示文摘出生后的心通过 hypertrophic 生长适应应力和超载,可能病理学或有益的一个过程(生理的肥大) 。生理的肥大改进心脏的性能在健康并且 diseased 个人,然而,宣传这有利改编的机制仍然保持糟糕定义。我们识别 cytokine cardiotrophin (CT1 ) 1 作为能够包括导致的导出 cardiomyocyte 的 angiogenic 信号的心肌层,和刺激的短暂、可逆的肥大概括心的生理的生长的特色的一个因素增加了由脉管形成。CT1 的能力从 caspase 激活的调停 CK2 的制止发源导致生理的肥大,阻止到无限制的病理学的生长的转变。外长的 CT1 蛋白质交货稀释了病理并且在正确的心失败的一个严格的模型恢复了可收缩的功能,建议为这难处理的心脏病的一种新奇处理选择。 | Mohammad Abdul-Ghani Colin Suen Baohua Jiang Yupu Deng Jonathan J Weldrick Charis Putinski Steve Brunette Pasan Femando Tom T Lee Peter Flynn Frans H H Leenen Patrick G Burgon Duncan J Stewar Lynn A Megeney | 2017 | Cell Research2017，27，10： | 8 |
| 4 | 诊断性试验和策略的证据质量和推荐强度的分级显示文摘GRADE系统能对诊断性试验或策略的证据质量和推荐强度进行分级。本文旨在阐释在此过程中如何考虑患者的重要结局, | Holger J Schünemann Andrew D Oxman Jan Brozek Paul Glasziou Roman Jaeschke Gunn E Vist John W Williams Jr Regina Kunz Jonathan Craig Victor M Montori Patrick Bossuyt Gordon H Guyatt 李晓 黄程 陈耀龙 李幼平 | 2009 | 中国循证医学杂志2009，9，5： | 7 |
| 5 | 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 |
| 6 | Management of diverticular disease is changing显示文摘结肠的憩室的疾病主要是人住在的疾病西洋化并且工业化国家。人住在工业化国家中的百分之六十个将开发结肠的憩室。它以前是稀罕的它发生在幼仔的 40 的年龄,而是对复杂并发症敏感的更多。在年龄 80,超过 65% 人有结肠的憩室。原因遗体不明确,却流行病的研究把它归因于饮食的纤维缺乏。憩室炎的原因仍然保持不明确,却新观察和假设建议它由于在肠墙中的慢性炎。肠休息和抗菌素的标准医药治疗仍然是推荐处理。然而,改变概念和新治疗 indicate 职业人员生命学可以是的反煽动性的代理人象 mesalamine 那样并且可能在弄短有用功课和也许阻止的复发。为为严重急性病的穿孔的标准外科疗法发展了以便二阶段的过程被推荐。另外, laparoscopic 外科证明了安全并且可以慢慢地成为选择的技术。 | Martin H Floch Jonathan A White | 2006 | World Journal of Gastroenterology2006，12，20： | 7 |
| 7 | Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial显示文摘 | Paul Y Kwo Eric J Lawitz Jonathan McCone Eugene R Schiff John M Vierling David Pound Mitchell N Davis Joseph S Galati Stuart C Gordon Natarajan Ravendhran Lorenzo Rossaro Frank H Anderson Ira M Jacobson Raymond Rubin Kenneth Koury Lisa D Pedicone Clifford | 2010 | The Lancet2010，，9742： | 3 |
| 8 | Chronic overexpression of PNPLA3^sup I148M^ in mouse liver causes hepatic steatosis显示文摘 | Li John Zhong Huang Yongcheng Karaman Ruchan Ivanova Pavlina T Brown H Alex Roddy Thomas Castro-Perez Jose Cohen Jonathan C Hobbs Helen H | 2012 | EN2012，，11： | 3 |
| 9 | Advanced non-alcoholic steatohepatitis cirrhosis: A high-risk population for pre-liver transplant portal vein thrombosis显示文摘AIM To examine if liver transplant recipients with high-risk non-alcoholic steatohepatitis(NASH) are at increased risk for pre-transplant portal venous thrombosis.METHODS Data on all liver transplants in the United States from February 2002 through September 2014 were analyzed. Recipients were sorted into three distinct groups: High-risk(age > 60, body mass index > 30 kg/m2, hypertension and diabetes), low-risk and non-NASH cirrhosis. Multivariable logistic regression models were constructed.RESULTS Thirty-five thousand and seventy-two candidates underwent liver transplantation and of those organ recipients, 465 were transplanted for high-risk and 2775 for lowrisk NASH. Two thousand six hundred and twentysix(7.5%) recipients had pre-transplant portal vein thrombosis; 66(14.2%) of the high-risk NASH group had portal vein thrombosis vs 328(11.8%) of the lowrisk NASH group. In general, all NASH recipients were less likely to be male or African American and more likely to be obese. In adjusted multivariable regression analyses, high-risk recipients had the greatest risk ofpre-transplant portal vein thrombosis with OR = 2.11(95%CI: 1.60-2.76, P < 0.001) when referenced to the non-NASH group.CONCLUSION Liver transplant candidates with high-risk NASH are at the greatest risk for portal vein thrombosis development prior to transplantation. These candidates may benefit from interventions to decrease their likelihood of clot formation and resultant downstream hepatic decompensating events. Prospective study is needed. | Jonathan G Stine Curtis K Argo Shawn J Pelletier Daniel G Maluf Stephen H Caldwell Patrick G Northup | 2017 | World Journal of Hepatology2017，9，3： | 2 |
| 10 | MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer显示文摘 | Nicola Valeri Chiara Braconi Pierluigi Gasparini Claudio Murgia Andrea Lampis Viola Paulus-Hock Jonathan R. Hart Lynn Ueno Sergei I. Grivennikov Francesca Lovat Alessio Paone Luciano Cascione Khlea M. Sumani Angelo Veronese Muller Fabbri Stefania Carasi H | 2014 | Cancer Cell2014，，： | 2 |
| 11 | Bioremediation of uranium-contaminated groundwater: a systems approach to subsurface biogeochemistry显示文摘 | Kenneth H Williams John R Bargar Jonathan R Lloyd Derek R Lovley | 2013 | Current Opinion in Biotechnology2013，，3： | 2 |
| 12 | Boceprevir for Chronic HCV Genotype 1 Infection in Patients with Prior Treatment Failure to Peginterferon/Ribavirin, including Prior Null Response显示文摘 | John M. Vierling Mitchell Davis Steven Flamm Stuart C. Gordon Eric Lawitz Eric M. Yoshida Joseph Galati Velimir Luketic Jonathan McCone Ira Jacobson Patrick Marcellin Andrew J. Muir Fred Poordad Lisa D. Pedicone Janice Albrecht Clifford Brass Anita Y.M. H | 2013 | Journal of Hepatology2013，，： | 2 |
| 13 | The elephant in uremia:Oxidant stress as a unifying concept of cardiovascular disease in uremia显示文摘 | Jonathan H Stenvinkel P Ikizler TA | 2002 | Kidney Int2002，62，： | 2 |
| 14 | Defying gravity显示文摘 | Jonathan H C Stephen F T | 1998 | Civil Engineering1998，68，2： | 1 |
| 15 | Concordance between functional magnetic resonance imaging and introperative language mapping显示文摘 | MAXIMILIAN I R JONATHAN D V SYED H | 1999 | Stereotact Funct Neurosurg1999，72，4： | 1 |
| 16 | Characterization of germ cells from pre-pubertal bull calves in prepara- tion forgerm cell transplantation显示文摘 | Murren H Rhonda J D Jonathan R | 2007 | Cell and Tissue Research2007，330，： | 1 |
| 17 | A new approach for outcrop characterization andgeostatistical analysis of a low-sinuosity fluvial-dominated succession using digital outcrop models:Upper Triassic Oukaimeden sandstone formation,central High Atlas,Morocco显示文摘 | Ivan F David H Jonathan R | 2009 | AAPG Bulletin2009，93，6： | 1 |
| 18 | Guidelines for Conscious Sedation and Monitoring During Gastrointestinal Endoscopy显示文摘 | J.Patrick Waring Todd H Baron William K Hirota Jay L Goldstein Brian C Jacobson Jonathan A Leighton J.Shawn Mallery Douglas O Faigel | 2003 | Gastrointestinal Endoscopy2003，，3： | 1 |
| 19 | Physical Activity Constrains among Latinos 显示文摘 | Michelle G H Myron F F Jonathan M C | 2013 | Journal of Leisure Re- search2013，45，1： | 1 |
| 20 | Using simula- tion to inteIpret a discrete time survival model in a complex biological system: fertility and lameness in dairy cows显示文摘 | Christopher D H Jonathan N H Martin J G | 2014 | Plos 0ne2014，9，8： | 1 |
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