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| 1 | Hepatocellular carcinoma surveillance:An evidence-based approach显示文摘Hepatocellular carcinoma(HCC) makes up 75%-85% of all primary liver cancers and is the fourth most common cause of cancer related death worldwide. Chronic liver disease is the most significant risk factor for HCC with 80%-90% of new cases occurring in the background of cirrhosis. Studies have shown that early diagnosis of HCC through surveillance programs improve prognosis and availability of curative therapies. All patients with cirrhosis and high-risk hepatitis B patients are at risk for HCC and should undergo surveillance. The recommended surveillance modality is abdominal ultrasound(US) given that it is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with non-alcoholic fatty liver disease(NAFLD). With the current obesity epidemic and rise in the prevalence of NAFLD, abdominal computed tomography or magnetic resonance imaging may be indicated as the primary screening modality in these patients. The addition of alpha-fetoprotein to a surveillance regimen is thought to improve the sensitivity of HCC detection.Further investigation of serum biomarkers is needed. Semiannual screening is the suggested surveillance interval. Surveillance for HCC is underutilized and low adherence disproportionately affects certain demographics such as nonCaucasian race and low socioeconomic status. | Patrick S Harris Ross M Hansen Meagan E Gray Omar I Massoud Brendan M McGuire Mohamed G Shoreibah | 2019 | World Journal of Gastroenterology2019，25，13： | 31 |
| 2 | 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 |
| 3 | 高产奶量的母猪有更高的采食量和体动员显示文摘选择能哺育更大窝产仔数的超高产母猪以提高产仔数,但是综合考虑这些现代母猪产奶量、采食量和体动员相互之间联系的研究还很有限。试验旨在研究什么样的母猪产奶量高、窝产仔数多,不同胎次有何影响,以及哺乳期生产性能对下一胎繁殖性能有何影响。选择565头1~4胎母猪,试验期从产前7 d至断奶。产后第2天每窝仔猪统一调整为14头。产前7 d、产后第2天和断奶时测定母猪体重和背膘厚度。产后第2天和断奶时称取仔猪窝重。计算变量之间的皮尔森相关系数,建立回归模型。母猪的平均日采食量(6.1±1.1)kg,仔猪每天窝增重(2.92±0.53)kg,每头母猪的平均断奶仔猪数(13.0±1.1)头。总的来讲,与2~4胎母猪相比,1胎母猪平均日采食量和产奶量更低,下一胎总产仔数也下降,这可能是因为初产母猪相比经产母猪会动用更多体储。仔猪每窝平均日增重与母猪的采食量、窝产仔数和体重损失呈正相关。1~4胎母猪整个哺乳期日采食量每提高1 kg,仔猪窝日增重提高220~440 g,母猪哺乳期体重下降6.6~13.9 kg。但是每天平均产奶量提高1 kg,第4胎母猪哺乳期体重损失减少4.3~21.0 kg。下一胎总产仔数与上一胎产仔数呈正相关。总之,高采食量和高体动员是高产奶量的先决条件。母猪可能已经非常接近他们身体饲料摄取的生理极限,因此,未来的研究应着眼于优化哺乳期超高产母猪的饲粮能量和营养浓度以及初产母猪和经产母猪之间的区别。 | Strathe A V Bruun T S Hansen C F 李元凤 | 2017 | 养猪2017，，4： | 8 |
| 4 | 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 |
| 5 | 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 |
| 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 | Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial显示文摘 | Harry LA Janssen Monika van Zonneveld Hakan Senturk Stefan Zeuzem Ulus S Akarca Yilmaz Cakaloglu Christopher Simon Thomas MK So Guido Gerken Robert A de Man Hubert GM Niesters Pieter Zondervan Bettina Hansen Solko W Schalm | 2005 | The Lancet . 2005 (9454)2005，，： | 2 |
| 8 | 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 |
| 9 | Intensive insulin therapy exerts anti-inflammatory effects in critically ill patients and counteracts the ad- verse effect of low mannose-binding lectin levels 显示文摘 | Hansen TK Thiel S Wouters PJ | 2003 | J Clin Endocrinol Metal2003，88，3： | 1 |
| 10 | Exercise lowers pain thresholdin chronic fatigue syndrome显示文摘 | Whiteside A Hansen S Chaudhuri A | 2004 | Pain2004，109，3： | 1 |
| 11 | Two-dimensionalgel electrophoretie analysis of vectorially labeled surface proteins of human spermatozoa 显示文摘 | Naaby Hansen S Flickinger C J Herr J C | 1997 | Biol Reprod1997，56，3： | 1 |
| 12 | 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 |
| 13 | Methane oxidation potentials and fluxes in agricultural soil:Effect of fertilization and soil compaction显示文摘 | Sitaula B K Hansen S | 2000 | Biogeochemistry2000，48，： | 1 |
| 14 | Circadian rhythms in serum and CSF cortisol of rhesus monkeys, and their modulation by timed injections of L-5- hydroxytryptophan 显示文摘 | UMBERKOMAN-WIITA B HANSEN S HERBERT J | 1981 | Brain Research1981，222，： | 1 |
| 15 | Clinical management of metabolic syndrome: report of the Ameri- can Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association conference on scientific issues related to management显示文摘 | Grundy S M Hansen B Smith S C Jr | 2004 | Circulation2004，109，4： | 1 |
| 16 | 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 |
| 17 | Do g-teen areas affect health? Results froma Danish survey on the use of green areas and health indicators显示文摘 | Nielsen T S Hansen K B | 2007 | Health Place2007，13，： | 1 |
| 18 | The first X-ray structural evidence demonstrating thiolate coordination in an organocobalt B12 model complex:implications for methionine syntheses显示文摘 | Polson S M Hansen L Marzilli L G | 1997 | Inorg Chem1997，36，2： | 1 |
| 19 | 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 |
| 20 | Bilirubin has wide spread inhib- itory effects on protein phosphorylation 显示文摘 | HANSEN T W MATHIESEN S B WALAAS S T | 1996 | Pediatr Res1996，39，6： | 1 |
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