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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 | 含有菊粉但不含羽扇豆的饲粮有助预防实验诱导的猪痢疾显示文摘猪痢疾是一种传染性黏膜出血的腹泻疾病,由定植于肠道的猪痢疾短螺旋体引起,能够诱发盲肠和结肠发炎。据报道饲料中添加菊苣根和甜羽扇豆可预防猪痢疾。本试验旨在验证是菊苣根中的菊粉而不是羽扇豆中的半乳糖起到保护作用的假设。 | Hansen C F Phillips N D La T.(等) 闫轶洁(译) 无 | 2010 | 养猪2010，，6： | 2 |
| 3 | Efficacy of SpyGlass^(TM)-directed biopsy compared to brush cytology in obtaining adequate tissue for diagnosis in patients with biliary strictures显示文摘AIM: To evaluate the diagnostic yield(inflammatory activity) and efficiency(size of the biopsy specimen) of SpyGlassTM-guided biopsy vs standard brush cytology in patients with and without primary sclerosing cholangitis(PSC).METHODS: At the University Medical Center Mainz, Germany, 35 consecutive patients with unclear biliarylesions(16 patients) or long-standing PSC(19 patients) were screened for the study. All patients underwent a physical examination, lab analyses, and abdominal ultrasound. Thirty-one patients with non-PSC strictures or with PSC were scheduled to undergo endoscopic retrograde cholangiography(ERC) and subsequent per-oral cholangioscopy(POC). Standard ERC was initially performed, and any lesions or strictures were localized. POC was performed later during the same session. The Boston Scientific SpyGlass SystemTM(Natick, MA, United States) was used for choledochoscopy. The biliary tree was visualized, and suspected lesions or strictures were biopsied, followed by brush cytology of the same area. The study endpoints(for both techniques) were the degree of inflammation, tissue specimen size, and the patient populations(PSC vs non-PSC). Inflammatory changes were divided into three categories: none, low activity, and high activity. The specimen quantity was rated as low, moderate, or sufficient.RESULTS: SpyGlassTM imaging and brush cytology with material retrieval were performed in 29 of 31(93.5%) patients(23 of the 29 patients were male). The median patient age was 45 years(min, 20 years; max, 76 years). Nineteen patients had known PSC, and 10 showed non-PSC strictures. No procedure-related complications were encountered. However, for both methods, tissues could only be retrieved from 29 pa-tients. In cases of inflammation of the biliary tract, the diagnostic yield of the SpyGlassTM-directed biopsies was greater than that using brush cytology. More tissue material was obtained for the biopsy method than for the brush cytology method(P = 0.021). The biopsies showed significantly more inflammatory characteristics and greater inflammatory activity compared to the cy-tological investigation(P = 0.014). The greater quantity of tissue samples proved useful for both PSC and non-PSC patients.CONCLUSION: SpyGlassTM imaging can be recom-mended for proper inflammatory diagnosis in PSC pa-tients. However, its value in diagnosing dysplasia wasnot addressed in this study and requires further investi-gation. | Johannes Wilhelm Rey Torsten Hansen Sebastian Dümcke Achim Tresch Katja Kramer Peter Robert Galle Martin Goetz Marcus Schuchmann Ralf Kiesslich Arthur Hoffman | 2014 | World Journal of Gastrointestinal Endoscopy2014，6，4： | 2 |
| 4 | 西双版纳傣族及上海汉族群体HLA-DR2相关的DR/DQ单倍型分析显示文摘对44名西双版纳傣族和9名上海地区汉族DK2阳性个体进行了与其相关的DR/DQ单倍型组合的分析。傣族群体中DRBI-DR2亚型分布以*1602与*1502为最常见,其等位基因频率分别为43.6%与,40.0%和汉族群体中以*1501为主明显不同。傣族群体中共检出10种与DR2相关联的DR/DQ单倍型;最常见的是DRB1*1602、DRB5*0101、DQA1*0102、DQB1*0502(34.5%)与汉族及其他群体明显不同,本研究表明傣族不仅具有高频率的DR2,而且与DR2相关联的DRB1、DRB5、DQA1、DQB1单倍型组合有其独特性。 | 范丽安 杨珏琴 姚芳娟 董建中 许玲娣 陈仁彪 M Sirkong R Vongrathna P Longta S Lekmak D Chandanayingyong A Smith J Hansen | 1995 | 中华医学遗传学杂志1995，12，3： | 2 |
| 5 | Interferon-γ inhibits ghrelin expression and secretion via a somatostatin-mediated mechanism显示文摘AIM:To investigate if and how the proinflammatory cytokine interferon γ(IFNγ) affects ghrelin expression in mice.METHODS:The plasma concentration of ghrelin,andgastric ghrelin and somatostatin expression,were examined in wild-type mice and mice infected with Helicobacter pylori(H.pylori).Furthermore,ghrelin expression was examined in two achlorhydric mouse models with varying degrees of gastritis due to bacterial overgrowth.To study the effect of IFNγ alone,mice were given a subcutaneous infusion of IFNγ for 7 d.Finally,the influence of IFNγ and somatostatin on the ghrelin promoter was characterized.RESULTS:H.pylori infection was associated with a 50% reduction in ghrelin expression and plasma concentration.Suppression of ghrelin expression was inversely correlated with gastric inflammation in achlorhdyric mouse models.Subcutaneous infusion of IFNγ suppressed fundic ghrelin mRNA expression and plasma ghrelin concentrations.Finally,we showed that the ghrelin promoter operates under the control of somatostatin but not under that of IFNγ.CONCLUSION:Gastric infection and inflammation is associated with increased IFNγ expression and reduced ghrelin expression.IFNγ does not directly control ghrelin expression but inhibits it indirectly via somatostatin. | Jesper AB Strickertsson Kristina BV DΦssing Anna JM Aabakke Hans-Olof Nilsson Thomas VO Hansen Ulrich Knigge Andreas Kjr Torkel Wadstrm Lennart Friis-Hansen | 2011 | World Journal of Gastroenterology2011，17，26： | 2 |
| 6 | Crisis in corporate America:The role of strategy 显示文摘 | HANSEN F D SMITH M C | 2003 | Business Horizons2003，15，1： | 1 |
| 7 | Thyroid function, morphology and autoimmunity in young patients with insulin-dependent diabetes mellitus 显示文摘 | Hansen D Bennedbaek FN Hansen LK | 1999 | Eur J Endocrinol1999，140，6： | 1 |
| 8 | Sperm chromatin structure integrity in liquid stored boar semen and its relationships with field fertility 显示文摘 | BOE HANSEN G B CHRISTENSEN P VIVJERG D | 2008 | Theriogenology2008，69，6： | 1 |
| 9 | Efficacy of topical silver against fungal burn wound pathogens显示文摘 | Lam K Hansen D | 1999 | Am J Infect Control1999，27，4： | 1 |
| 10 | Thalassiolins A-C: new marine-derived inhibitors of HIV eDNA integrase显示文摘 | Rowley D C Hansen M S T Rhodes D | 2002 | Bioorg Med Chen2002，10，： | 1 |
| 11 | Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60显示文摘 | Hansen JJ Dǔrr A Corunu-Rebeix I | 2002 | Am J Hum Genet2002，70，5： | 1 |
| 12 | Yeast beta-glucan amplifies phagocyte killing of iC3b-opsonized tumor cells via complement receptor 3-Syk-phosphatidylinositol 3-kinase pathway显示文摘 | Li B Allendorf D J Hansen R | 2006 | J Immunol2006，177，3： | 1 |
| 13 | The design of systems to control actively periodic sound transmission into enclosed spaces, Part II: Mechanisms and trends显示文摘 | Snyder S D Hansen C H | 1994 | J Sound and Vibration1994，170，4： | 1 |
| 14 | Indentation fracture response and damage resistance of Al2O3-ZrO2 compositesstrengthened by transformation-induced residual stresses显示文摘 | Hansen J J Cutler R A Shetty D K | 1988 | Journal of the American Ceramic Society1988，171，12： | 1 |
| 15 | Early enteral supply of fiber and Lactobaeiili versus conventional nutrition: A controlled trial inpatients with major abdominal surgery显示文摘 | Rayes N Hansen S Seehofer D | 2002 | Nutrition2002，18，78： | 1 |
| 16 | Continuous low- to moderate intensity exercise training is as effective as moderate- to high-intensity exercise training at lowering blood HbA (1c) in obese type 2 diabetes patients 显示文摘 | Hansen D Dendale P Jonkers RA | 2009 | Diabetologia2009，52，： | 1 |
| 17 | Genetically null mice reveal a central role for epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development显示文摘 | Hansen L A Alexander N Hogan M E Sundberg J P Dlugosz A Threadgill D W Magnuson T Yuspa S H | | 0，，06： | 1 |
| 18 | Electronic doors to education: Study of high school website accessi bility in Iowa显示文摘 | KLEIN D MYHILL W HANSEN L | 2003 | Behavioral sciences the law2003，21，1： | 1 |
| 19 | Ecoefficiency: Defining a role for environmental cost management显示文摘 | Bumett R D D R Hansen | 2008 | Accounting Organiza- tions and Society2008，33，6： | 1 |
| 20 | Fault ride-through capability of DFIG wind turbines显示文摘 | HANSEN A D MICHALKE G | 2007 | Renewable Energy2007，32，1： | 1 |
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