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| 1 | Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy显示文摘AIM:To characterize development of diet-induced nonalcoholic steatohepatitis(NASH)by performing live biopsy in wild-type and genetically obese mice.METHODS:Male wild-type C57BL/6J(C57)mice(DIO NASH)and male Lep ob/Lep ob(ob/ob)mice(ob/ob-NASH were maintained on a diet high in trans-fat(40%)fructose(22%)and cholesterol(2%)for 26 and 12 wk respectively.A normal chow diet served as control in C57 mice(lean chow)and ob/ob mice(ob/ob chow)After the diet-induction period,mice were liver biopsied and a blinded histological assessment of steatosis and fibrosis was conducted.Mice were then stratified into groups counterbalanced for steatosis score and fibrosi stage and continued on diet and to receive daily PO dosing of vehicle for 8 wk.Global gene expression in liver tissue was assessed by RNA sequencing and bioin formatics.Metabolic parameters,plasma liver enzyme and lipids(total cholesterol,triglycerides)as well a hepatic lipids and collagen content were measured b biochemical analysis.Non-alcoholic fatty liver disease activity score(NAS)(steatosis/inflammation/ballooningdegeneration)and fibrosis were scored.Steatosis and fibrosis were also quantified using percent fractional area.RESULTS:Diet-induction for 26 and 12 wk in DIONASH and ob/ob-NASH mice,respectively,elicited progressive metabolic perturbations characterized by increased adiposity,total cholesterol and elevated plasma liver enzymes.The diet also induced clear histological features of NASH including hepatosteatosis and fibrosis.Overall,the metabolic NASH phenotype was more pronounced in ob/ob-NASH vs DIO-NASH mice.During the eight week repeated vehicle dosing period,the metabolic phenotype was sustained in DIO-NASH and ob/ob-NASH mice in conjunction with hepatomegaly and increased hepatic lipids and collagen accumulation.Histopathological scoring demonstrated significantly increased NAS of DIO-NASH mice(0 vs4.7±0.4,P<0.001 compared to lean chow)and ob/ob-NASH mice(2.4±0.3 vs 6.3±0.2,P<0.001compared to ob/ob chow),respectively.Furthermore,fibrosis stage was significantly elevated for DIO-NASH mice(0 vs 1.2±0.2,P<0.05 compared to lean chow)and ob/ob NASH(0.1±0.1 vs 3.0±0.2,P<0.001compared to ob/ob chow).Notably,fibrosis stage was significantly(P<0.001)increased in ob/ob-NASH mice,when compared to DIO-NASH mice.CONCLUSION:These data introduce the obese dietinduced DIO-NASH and ob/ob-NASH mouse models with biopsy-confirmed individual disease staging as a preclinical platform for evaluation of novel NASH therapeutics. | Maria Nicoline Baandrup Kristiansen Sanne Skovgard Veidal Kristoffer Tobias Gustav Rigbolt Kirstine Sloth Tolbol Jonathan David Roth Jacob Jelsing Niels Vrang Michael Feigh | 2016 | World Journal of Hepatology2016，8，16： | 10 |
| 2 | Stage and size using magnetic resonance imaging and endosonography in neoadjuvantly-treated rectal cancer显示文摘AIM: To assess the stage and size of rectal tumours using 1.5 Tesla (1.5T) magnetic resonance imaging (MRI) and three-dimensional (3D) endosonography (ERUS). METHODS: In this study, patients were recruited in a phaseⅠ/Ⅱ trial of neoadjuvant chemotherapy for biopsy-proven rectal cancer planned for surgical resection with or without preoperative radiotherapy. The feasibility and accuracy of 1.5T MRI and 3D ERUS were compared with the histopathology of the fixed surgical specimen (pathology) to determine the stage and size of the rectal cancer before and after neoadjuvant chemotherapy. A Philips Intera 1.5T with a cardiac 5-channel synergy surface coil was used for the MRI, and a B-K Medical Falcon 2101 EXL 3D-Probe was used at 13 MHz for the ERUS. Our hypothesis was that the staging accuracy would be the same when using MRI, ERUS and a combination of MRI and ERUS. For the combination, MRI was chosen for the assessment of the lymph nodes, and ERUS was chosen for the assessment of perirectal tissue penetration. The stage was dichotomised into stageⅠ and stage Ⅱ or greater. The size was measured as the supero-inferior length and the maximal transaxial area of the tumour. RESULTS: The staging feasibility was 37 of 37 for the MRI and 29 of 36 for the ERUS, with stenosis as a limiting factor. Complete sets of investigations were available in 18 patients for size and 23 patients for stage. The stage accuracy by MRI, ERUS and the combination of MRI and ERUS was 0.65, 0.70 and 0.74, respectively, before chemotherapy and 0.65, 0.78 and 0.83, respectively, after chemotherapy. The improvement of the post-chemotherapy staging using the combination of MRI and ERUS compared with the staging using MRI alone was significant (P = 0.046). The post-chemotherapy understaging frequency by MRI, ERUS and the combination of MRI and ERUS was 0.18, 0.14 and 0.045, respectively, and these differences were non-significant. The measurements of the supero-inferior length by ERUS compared with MRI were within 1.96 standard deviations of the difference between the methods (18 mm) for tumours smaller than 50 mm. The agreement with pathology was within 1.96 standard deviations of the difference between imaging and pathology for all tumours with MRI (15 mm) and for tumours that did not exceed 50 mm with ERUS (22 mm). Tumours exceeding 50 mm in length could not be reliably measured by ERUS due to the limit in the length of each recording. CONCLUSION: MRI is preferable to use when assessing the size of large or stenotic rectal tumours. However, staging accuracy is improved by combining MRI with ERUS. | Torbjrn Swartling Peter Klebo Kristoffer Derwinger Bengt Gustavsson Gran Kurlberg | 2013 | World Journal of Gastroenterology2013，19，21： | 9 |
| 3 | Large-area nanopatterned graphene for ultrasensitive gas sensing显示文摘 | Alberto Cagliani David Micheal Angus Mackenzie Lisa Katharina Tschammer Filippo Pizzocchero Kristoffer Almdal Peter Boggild | 2014 | Nano Research2014，7，5： | 7 |
| 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 | 某浅水湖型水源地土臭素(GSM)和2-甲基异莰醇(2-MIB)的变化规律显示文摘以2016年某水源地水样为研究对象,对该水源水的致臭物质2-甲基异莰醇(2-MIB)、土臭素(GSM)以及藻类含量进行检测。通过环境因素相关性分析,构建水源水季节预警机制。研究表明:2-MIB与GSM的含量在夏秋季比较高,在冬春季相对较低;同时,2-MIB的含量在7月、8月远远高于臭阈值,这两种物质在3月、4月浓度均有所上升,与藻类浓度的变化规律基本一致。 | 张建芳 顾青清 符策竿 张泾凯 牛璐瑶 Kristoffer OOMs 刘洪波 | 2018 | 净水技术2018，37，11： | 5 |
| 7 | 当前围手术期处理模式:北欧五国结直肠外科医生调查显示文摘 | Kristoffer Lassen Pascal Hannemann Olle Ljungqvist Ken Fearon Cornelis H C Dejong Maarten F von Meyenfeldt Jonatan Hausel Jonas Nygren Jens Andersen Arthur Revhaug 王东 | 2005 | 英国医学杂志中文版2005，8，6： | 3 |
| 8 | Corundum formation by metasomatic reactions in Archean metapelite,SW Greenland:Exploration vectors for ruby deposits within high-grade greenstone belts显示文摘Corundum(ruby-sapphire) is known to have formed in situ within Archean metamorphic rocks at several localities in the North Atlantic Craton of Greenland. Here we present two case studies for such occurrences:(1) Maniitsoq region(Kangerdluarssuk), where kyanite paragneiss hosts ruby corundum, and(2)Nuuk region(Stor?), where sillimanite gneiss hosts ruby corundum. At both occurrences, ultramafic rocks(amphibole-peridotite) are in direct contact with the ruby-bearing zones, which have been transformed to mica schist by metasomatic reactions. The bulk-rock geochemistry of the ruby-bearing rocks is consistent with significant depletion of SiO_2 in combination with addition of Al_2O_3, MgO, K_2O,Th and Sr relative to an assumed aluminous precursor metapelite. Phase equilibria modelling supports ruby genesis from the breakdown of sillimanite and kyanite at elevated temperatures due to the removal of SiO_2. The juxtaposition of relatively silica-and aluminum-rich metasedimentary rocks with low silica ultramafic rocks established a chemical potential gradient that leached/mobilized SiO_2 allowing corundum to stabilize in the former rocks. Furthermore, addition of Al_2O_3 via a metasomatic reaction is required, because Al/Ti is fractionated between the aluminous precursor metapelites and the resulting corundum-bearing mica schist. We propose that Al was mobilized either by complexation with hydroxide at alkaline conditions, or that Al was transported as K-Al-Si-O polymers at deep crustal levels.The three main exploration vectors for corundum within Archean greenstone belts are:(1) amphiboliteto granulite-facies metamorphic conditions,(2) the juxtaposition of ultramafic rocks and aluminous metapelite, and(3) mica-rich reactions zones at their interface. | Chris Yakymchuk Kristoffer Szilas | 2018 | Geoscience Frontiers2018，9，3： | 2 |
| 9 | 在 vivo 长期单个房间的追踪在老鼠的成年人出生的 juxtaglomerular 房间揭示迁居模式的开关嗅觉的灯泡显示文摘成年人出生的细胞的行为能容易仍然在他们的本国的微型环境在细胞文化或在单个哺乳动物的成年人出生的细胞的更低的模型有机体,而是纵的观察被监视证明是挑战。这里,我们证实了一条途径把光房间放称为系统为在 vivo 长期房间用重复 angiography 标记的单个房间的追踪,它集成 red-green-blue。由把这条途径与相结合在 vivo 二光子的成像技术,我们描绘了在里面在嗅觉的灯泡的成年人出生的神经原的 vivo 迁居模式。与在灯泡以内的成年人出生的房间的仅仅的光线的移植的传统的看法相对照,我们在他们的目的地层在到达之上发现房间从光线的移植交换到长距离的那 juxtaglomerular 侧面的移植。这唯一的长途的侧面的迁居有特征时间(定期而不断被迫停) 并且空间(迁移,单向性或 multidirectional ) 模式,与处于迁居速度的清楚的房间年龄依赖者减少。成年人出生的房间的活跃迁居与起始的命运决心的时间时期与一致并且是可能的影响成年人出生的房间,他们的气味应答,以及他们的幸存率的集成地点。 | Yajie Liang Kaizhen Li Kristoffer Riecken Anatoliy Maslyukov Diego Gomez-Nicola Yury Kovalchuk Boris Fehse Olga Garaschuk | 2016 | Cell Research2016，26，7： | 2 |
| 10 | Tumour differentiation grade is associated with TNM staging and the risk of node metastasis in colorectal can- cer显示文摘 | Derwinger kristoffer Kodeda karl Bexe-lindskog elinor | 2009 | Acta Oncologica2009，49，1： | 1 |
| 11 | Early microbial translocation blockade reduces SIV-mediated inflammation and viral replication显示文摘 | Kristoff Jan Haret-Richter George Ma Dongzhu Ribeiro Ruy M Xu Cuiling Cornell Elaine Stock Jennifer L He Tianyu Mobley Adam D Ross Samantha Trichel Anita Wilson Cara Tracy Russell Landay Alan Apetrei Cristian Pandrea Ivona | 2014 | Journal of Clinical Investigation2014，，： | 1 |
| 12 | Examples of high-frequency EPR studies in bioinorganic chemistry显示文摘 | K. Kristoffer Andersson Peter P. Schmidt Bettina Katterle Kari R. Strand Amy E. Palmer Sang-Kyu Lee Edward I. Solomon Astrid Gr?slund Anne-Laure Barra | 2003 | JBIC Journal of Biological Inorganic Chemistry2003，，3： | 1 |
| 13 | Morphological differences in BMP-2-induced ectopic bone between solid and crushed hyaluronan hydrogel templates显示文摘 | Gry Hulsart-Billstr?m Sonya Piskounova Lars Gedda Britt-Marie Andersson Kristoffer Bergman J?ns Hilborn Sune Larsson Tim Bowden | 2013 | Journal of Materials Science: Materials in Medicine2013，，5： | 1 |
| 14 | The effect of organic matter on multi-spectral properties of soils显示文摘 | Baumgardner M F Kristoff S J Johannsen C J | 1970 | Proc Indiana Acad Sci1970，79，： | 1 |
| 15 | Clicked tacrine conjugates as acetylcholinesterase and β-amyloid directed compounds 显示文摘 | Myriam O Kristoffer B Monika V | 2011 | Org Biomol Chem2011，9，4： | 1 |
| 16 | 常用药剂对污水中硫化物的去除效果显示文摘污水中的硫化物具有毒性大、极易挥发,金属腐蚀性强等特点,危害水和大气生态环境,因此污水中硫化物的去除也是污水处理厂日常工作的重点。研究污水厂常用药剂对污水中硫化物的去除效果,找到拥有最佳去除效果的药剂和最佳投放量,选择聚合氯化铁铁药剂、硫酸铝溶液、石灰粉末作混凝剂进行试验。分析发现,硫酸铝和石灰对硫化物的去除无作用,选择聚合氯化铁作混凝剂对污水中的硫化物有不错的去除效果。研究硫化物在混凝操作中的去除率,确定其是否可以在此混凝操作之后达到硫化物排放标准。硫化物浓度为0.34 mg/L、聚铁投加量为1 m L时,硫化物去除率最高,可达97.9%。 | 徐超 吕弈成 符策竿 Kristoffer OOMs 刘洪波 | 2018 | 净水技术2018，37，7： | 1 |
| 17 | Perforated colonic diverticular disease: the importance of NSAIDs, opioids, corticosteroids, and calcium channel blockers显示文摘 | Kristoffer Piekarek Leif A. Israelsson | 2008 | International Journal of Colorectal Disease2008，，12： | 1 |
| 18 | Finite element simulation of the tube hydroforming process-bending,preforming and hydroforming显示文摘 | Kristoffer Trana | | 0，，117： | 1 |
| 19 | Enviromental Stress Cracking Resistance Behaviour of Polycarbonate in Different Chemicals by Determination of the Timedependence of Stress at Constant Strains 显示文摘 | Lutfi F A Kell M Kristoffer A | 2003 | Polymer Degradation and Stability2003，82，3： | 1 |
| 20 | Perforated colonic diverticular disease: the importance of NSAIDs, opioids, corticosteroids, and calcium channel blockers显示文摘 | Kristoffer Piekarek Leif A. Israelsson | 2008 | International Journal of Colorectal Disease2008，，12： | 1 |
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