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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 | 人体-座椅接触面测量参数的研究初探显示文摘文中介绍了一种集力、温度和湿度传感器信息的座椅舒适度检测系统。传感器的布放采用已发表文章中所介绍的布放方式:温度和湿度传感器分别放置在左、右腿和尾臀骨下方;4个力传感器分别放在左、右腿和左、右坐骨结节的下方。在进行人体实验前,对力、温度和湿度传感器的输出一致性进行了测试。测量数据显示:温度传感器标准方差为±0.2℃;湿度传感器标准方差为±0.3%,压力传感器标准方差为±0.09 V(其中加载负荷5 kg~15 kg,力传感器输出电压的变化为3.67~4.31 V),这表明所有的传感器具有一致的输出特性。在三天内,共有10人/次利用该检测系统对3种坐垫(泡沫、木质和压模坐垫)的舒适度进行了评估。为了避免次序效应对测量结果的影响,整个实验采用了拉丁方设计方法。通过将坐姿调整时间、最大温度和平均相对湿度与舒适度主观评测问卷进行对比分析,结果表明传感器的原始数据和相关参数的变化与人对座椅舒适度的主观评价之间存在一定的联系。 | 刘卓夫 罗中明 Vincenzo Cascioli Louise Mazzeo Andrewl Heusch Peter W M^c Carthy | 2011 | 仪表技术与传感器2011，，1： | 3 |
| 3 | Percutaneous pulomonary valve implantation in humans results in 59 consecutive patients 显示文摘 | Sachin K Louise C Andrew T | 2005 | Circulation2005，111，： | 1 |
| 4 | Stimulating creative play in children with autism through sandplay显示文摘 | Lucy Lu Fiona Petersen Louise Lacroix Cécile Rousseau | 2009 | The Arts in Psychotherapy2009，，1： | 1 |
| 5 | Loneliness and pathways to disease显示文摘 | Louise C Hawkly J Cacioppo T | 2003 | Brain Behavior and Immunity2003，17，： | 1 |
| 6 | Correction for the static shift in magnetotellurics using transient electromagnetic sounding显示文摘 | Ben K S James C W Louise P | 1988 | Geophyisic1988，53，11： | 1 |
| 7 | The potential use of cereal(1→3,1→4)-β-D-glucans as functional food ingredients显示文摘 | CHARLES S B LOUISE J C | 2005 | Journal of Cereal Science2005，42，： | 1 |
| 8 | Trimalleolar Fractures显示文摘 | W C WARNER LOUIS A. FARBER | 1965 | Southern Medical Journal1965，，10： | 1 |
| 9 | Synthesis and processing of the trasmembrane envelope protein of equine infectious anemia virus显示文摘 | Nancy R Louise H Raymond C S | 1990 | J Virol1990，64，： | 1 |
| 10 | Sedation for endoscopy:the safe use of propofol by general practitioner sedationists显示文摘 | Anthony C Louise L Hillman C | 2002 | Med J Aust2002，1764，： | 1 |
| 11 | Handhygiene 显示文摘 | Louise T Barry C Sheldon S | 2001 | Br Med J2001，323，7310： | 1 |
| 12 | Sedation for endoscopy: The safe use of propofol by general practitioner sedationists显示文摘 | CLARKE A C LOUISE C HILLMAN L C | 2002 | Medical Journal of Australia2002，176，4： | 1 |
| 13 | Challenges to effective cancer control in China, India, and Russia显示文摘 | Paul E Goss Kathrin Strasser-Weippl Brittany L Lee-Bychkovsky Lei Fan Junjie Li Yanin Chavarri-Guerra Pedro E R Liedke C S Pramesh Tanja Badovinac-Crnjevic Yuri Sheikine Zhu Chen You-lin Qiao Zhiming Shao Yi-Long Wu Daiming Fan Louis W C Chow Jun Wang Qio | 2014 | Lancet Oncology2014，，5： | 1 |
| 14 | Piplartine, an amide alkaloid from Piper tuberculatum , presents anxiolytic and antidepressant effects in mice显示文摘 | F. Cícero Bezerra Felipe Jucélio Trajano Sousa Filho Louise Emanuele de Oliveira Souza Jefferson Alexandre Silveira Daniel Esdras de Andrade Uchoa Edilberto Rocha Silveira Otília Deusdênia Loiola Pessoa Glauce S. de Barros Viana | 2006 | Phytomedicine2006，，： | 1 |
| 15 | Learning from positive examples when the negative class is undetermined microRNA gene identification 显示文摘 | MALIK YOUSEF SEGUN JUNG LOUISE C SHOWE | 2008 | Algorithms For Molecular Biology2008，3，1： | 1 |
| 16 | Thoracic epidural anesthesia for cardiac surgeryahe effects on tracheal intubation time and length of hospital stay显示文摘 | Mark C Louise C Richard H | 2002 | Anesth Analg2002，94，： | 1 |
| 17 | Antimicrobial peptide defenses against chytridiomycosis,an emerging infectious disease of amphibian populations显示文摘 | Louise A Rollins-Smith J M C | | 0，，： | 1 |
| 18 | The terminology of the 2012 Atlanta consensus conference on post-inflammatory collections after acute pancreatitis:An assessment of utilization in practice显示文摘To the Editor The report of the 1992 Atlanta consensus conference provided a framework for standardization of the terminology for description of acute pancreatitis and its complications[1].Terms such as“pancreatic phlegmon”which had historically been subjected to differential interpretation were discontinued and modern terminology was introduced[1].With subsequent clinical usage and with the accrual of new knowledge it became clear that further changes were necessary. | Santhalingam Jegatheeswaran Louise M Finch Maya C Siriwardena Ajith K Siriwardena | 2022 | Hepatobiliary & Pancreatic Diseases International2022，21，5： | 1 |
| 19 | Impact of brand personality on three major relational consequences ( trust, attachment, and commitment to the brand 显示文摘 | Louis D and Lombart C | 2010 | The Journal of Product and Brand Management2010，19，2： | 1 |
| 20 | Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial显示文摘 | Raj R Makkar Rachel R Smith Ke Cheng Konstantinos Malliaras Louise EJ Thomson Daniel Berman Lawrence SC Czer Linda Marbán Adam Mendizabal Peter V Johnston Stuart D Russell Karl H Schuleri Albert C Lardo Gary Gerstenblith Eduardo Marbán | 2012 | The Lancet2012，，9819： | 1 |
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