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| 1 | 预期寿命估计对脊柱转移瘤手术选择与预后预测的临床意义显示文摘背景与目的:目前,临床上对脊柱转移瘤患者是否采取手术治疗以及如何选择手术仍然存在较大的争议。预期寿命的估计是手术选择的决定因素之一。本研究旨在评价Tokuhashi和Tomita评分系统这两种常用的预期寿命估计方法对硬膜外脊柱转移瘤患者手术选择与预后预测的临床价值。方法:对2001年1月至2004年4月丹麦奥胡斯大学医院脊柱外科中心收治的169例硬膜外脊柱转移瘤入组患者,术前用Tokuhashi与Tomita评分系统进行评分以及估计预期寿命,并结合Tomita脊柱肿瘤分型,选择实施手术分级治疗。术后6个月、12个月以及24个月分别进行前瞻性随访观察。对在预期寿命为“3个月内死亡”、“6个月内死亡”以及“12个月内死亡”的患者通过Tokuhashi与Tomita评分系统绘制受试者作业特征曲线(receiveroperatingcharacteristiccurves,ROC曲线),比较两个评分系统对预期寿命估计的准确性。同时采用Kaplan-Meier生存曲线分析法,计算Tokuhashi和Tomita评分系统各分数段患者术后的实际平均生存时间。结果:预期寿命分别为“3个月内死亡”、“6个月内死亡”以及“12个月内死亡”的病例ROC曲线分析显示,Tomita评分系统与Tokuhashi评分系统之间的差异均无显著性(各组P值分别为0.16、0.47与0.38)。Kaplan-Meier生存曲线分析显示,Tomita评分系统在4~7分之间对预后估计过高,Tokuhashi评分系统在0~8分之间对预后估计过低。结论:Tokuhashi和Tomita评分系统均可成功地预测脊柱转移瘤患者术后预后的情况。Tokuhashi评分系统可较为准确地预测生存期较短的患者,从而避免对这类患者做不必要的大手术。 | 邹学农 Anders Grejs 李海声 Kristian Hφy Ebbe S Hansen Cody Bünger | 2006 | 癌症2006，25，11： | 18 |
| 2 | 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 |
| 3 | Metabolic and hepatic effects of liraglutide,obeticholic acid and elafibranor in diet-induced obese mouse models of biopsy-confirmed nonalcoholic steatohepatitis显示文摘AIM To evaluate the pharmacodynamics of compounds in clinical development for nonalcoholic steatohepatitis(NASH) in obese mouse models of biopsy-confirmedNASH.METHODS Male wild-type C57 BL/6 J mice(DIO-NASH) and Lep^(ob/ob)(ob/ob-NASH) mice were fed a diet high in trans-fat(40%), fructose(20%) and cholesterol(2%) for 30 and 21 wk, respectively. Prior to treatment, all mice underwent liver biopsy for confirmation and stratification of liver steatosis and fibrosis, using the nonalcoholic fatty liver disease activity score(NAS) and fibrosis staging system. The mice were kept on the diet and received vehicle, liraglutide(0.2 mg/kg, SC, BID), obeticholic acid(OCA, 30 mg/kg PO, QD), or elafibranor(30 mg/kg PO, QD) for eight weeks. Within-subject comparisons were performed on changes in steatosis, inflammation, ballooning degeneration, and fibrosis scores. In addition, compound effects were evaluated by quantitative liver histology, including percent fractional area of liver fat, galectin-3, and collagen 1 a1.RESULTS Liraglutide and elafibranor, but not OCA, reduced body weight in both models. Liraglutide improved steatosis scores in DIO-NASH mice only. Elafibranor and OCA reduced histopathological scores of hepatic steatosis and inflammation in both models, but only elafibranor reduced fibrosis severity. Liraglutide and OCA reduced total liver fat, collagen 1 a1, and galectin-3 content, driven by significant reductions in liver weight. The individual drug effects on NASH histological endpoints were supported by global gene expression(RNA sequencing) and liver lipid biochemistry.CONCLUSION DIO-NASH and ob/ob-NASH mouse models show distinct treatment effects of liraglutide, OCA, and elafibranor, being in general agreement with corresponding findings in clinical trials for NASH. The present data therefore further supports the clinical translatability and utility of DIO-NASH and ob/ob-NASH mouse models of NASH for probing the therapeutic efficacy of compounds in preclinical drug development for NASH. | Kirstine S Tolbol Maria NB Kristiansen Henrik H Hansen Sanne S Veidal Kristoffer TG Rigbolt Matthew P Gillum Jacob Jelsing Niels Vrang Michael Feigh | 2018 | World Journal of Gastroenterology2018，24，2： | 5 |
| 4 | Effectiveness of a Passive-active Vibration Isolation System with Actuator Constraints显示文摘In the prediction of active vibration isolation performance,control force requirements were ignored in previous work.This may limit the realization of theoretically predicted isolation performance if control force of large magnitude cannot be supplied by actuators.The behavior of a feed-forward active isolation system subjected to actuator output constraints is investigated.Distributed parameter models are developed to analyze the system response,and to produce a transfer matrix for the design of an integrated passive-active isolation system.Cost functions comprising a combination of the vibration transmission energy and the sum of the squared control forces are proposed.The example system considered is a rigid body connected to a simply supported plate via two passive-active isolation mounts.Vertical and transverse forces as well as a rotational moment are applied at the rigid body,and resonances excited in elastic mounts and the supporting plate are analyzed.The overall isolation performance is evaluated by numerical simulation.The simulation results are then compared with those obtained using unconstrained control strategies.In addition,the effects of waves in elastic mounts are analyzed.It is shown that the control strategies which rely on unconstrained actuator outputs may give substantial power transmission reductions over a wide frequency range,but also require large control force amplitudes to control excited vibration modes of the system.Expected power transmission reductions for modified control strategies that incorporate constrained actuator outputs are considerably less than typical reductions with unconstrained actuator outputs.In the frequency range in which rigid body modes are present,the control strategies can only achieve 5–10 dB power transmission reduction,when control forces are constrained to be the same order of the magnitude as the primary vertical force.The resonances of the elastic mounts result in a notable increase of power transmission in high frequency range and cannot be attenuated by active control.The investigation provides a guideline for design and evaluation of active vibration isolation systems. | SUN Lingling SUN Wei SONG Kongjie HANSEN Colin H | 2014 | Chinese Journal of Mechanical Engineering2014，27，3： | 5 |
| 5 | Trustworthiness as a Source of Competitive Advantage显示文摘 | Joy B Barney Mark H Hansen | 1994 | Strategic Management Journal1994，，： | 3 |
| 6 | Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source显示文摘BACKGROUND The trans-fat containing AMLN(amylin liver non-alcoholic steatohepatitis,NASH)diet has been extensively validated in C57BL/6J mice with or without the Lep^ob/Lep^ob(ob/ob)mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH.Due to a recent ban on trans-fats as food additive,there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57BL/6J mice.AIM To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat.METHODS Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-fat(Primex shortening)substituted by equivalent amounts of palm oil[Gubra amylin NASH,(GAN)diet]for 8,12 and 16 wk.C57BL/6J mice were fed the same diets for 28 wk.AMLN and GAN diets had similar caloric content(40%fat kcal),fructose(22%)and cholesterol(2%)level.RESULTS The GAN diet was more obesogenic compared to the AMLN diet and impaired glucose tolerance.Biopsy-confirmed steatosis,lobular inflammation,hepatocyte ballooning,fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMLN diet.C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets.CONCLUSION Substitution of Primex with palm oil promotes a similar phenotype of biopsyconfirmed NASH in ob/ob and C57BL/6J mice,making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments. | Michelle L Boland Denise Oro Kirstine S T■lb■l Sebastian T Thrane Jens Christian Nielsen Taylor S Cohen David E Tabor Fiona Fernandes Andrey Tovchigrechko Sanne S Veidal Paul Warrener Bret R Sellman Jacob Jelsing Michael Feigh Niels Vrang James L Trevaskis Henrik H Hansen | 2019 | World Journal of Gastroenterology2019，25，33： | 3 |
| 7 | Detection of cesarean scars by transvaginal ultrasound显示文摘 | Vanessa Armstrong Wendy F Hansen Bradley J Van Voorhis Craig H Syrop | 2002 | Obstetrics & Gynecology2002，，1： | 2 |
| 8 | Model selection and the principle of minimum description length显示文摘 | Hansen M H Yu B | 1998 | Journal of the American Statistical Association1998，96，454： | 2 |
| 9 | Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: result of a large,randomized, multinational, multicenter, phase Ⅲ study 显示文摘 | Hansen SW | 2000 | J Clin Oncol2000，18，17： | 1 |
| 10 | Nucleo- tide sequence of pOLA52 A conjugative IncX1 plasmid from Escherichia coli which enable biofilm formation and multidrug efflux 显示文摘 | NORMAN A HANSEN L H SHE Qun-xin | 2008 | Plasmid2008，60，1： | 1 |
| 11 | 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 |
| 12 | The Problem of Nonresponse in Sample Surveys显示文摘 | Hansen M H Hurwitz W N | 1946 | Journal of the American Statistical Association1946，，41： | 1 |
| 13 | Correlation between N-acetyl aspartate levels and histopathologic changes in cortical infarcts of mice after middle cerebral artery occlusion显示文摘 | Sager TN Hansen AJ Laursen H | 2000 | J Cereb Blood Flow Metab2000，20，： | 1 |
| 14 | Fundamentals of transorbital sonographic evaluation of optic nerve sheath expansion under intracranial hypertension II patient study显示文摘 | Helmke K Hansen H | 1996 | Pediatr Radiol1996，26，： | 1 |
| 15 | Combination chemotherapy of advanced lung cancer:a randomizedtrial显示文摘 | Hansen H H Selawry O S Simon K | 1976 | Cancer1976，38，6： | 1 |
| 16 | Occlusal changes during and after Herbst treatment:a cephalometric investigation显示文摘 | Pancherz H Hansen K | 1986 | Eur J Orthod1986，8，： | 1 |
| 17 | Renal biopsy finding in long term cyclosporin treatment of psoriasis显示文摘 | Zachariae H Kragballe K Hansen HE | 1997 | Br J Dermatol1997，136，： | 1 |
| 18 | Movement of foliar boron out of leaves and accumulation in flower buds and flower parts of Italion prune显示文摘 | HANSEN M H CHAPLIN P J | 1985 | HortScience1985，20，： | 1 |
| 19 | Enforced mobilization,early oral feeding, and balanced analgesia improve convalescence after colorectal surgery 显示文摘 | Henriksen M G Jensen M B Hansen H V | 2002 | Nutrition2002，18，2： | 1 |
| 20 | Bacterial interactions in early life stage of marine cold water fish显示文摘 | Hansen G H Olafsen J A | 1999 | Microbial Ecology1999，38，： | 1 |
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