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| 1 | Rectal nitric oxide as biomarker in the treatment of inflammatory bowel disease: Responders versus nonresponders显示文摘瞄准:探索直肠的氮的氧化物(没有) 作为处理的简历标记,在 ulcerative (UC ) 和 Crohn 的反应是疾病(CD ) ,并且检验在之间的关系直肠没有,没有 synthases (NOS ) 的粘膜表示,和支持 inflammatory cytokines。方法:有 UC 的 22 个病人并且 24 在类固醇治疗期间与 CD 被监视。直肠没有层次被测量,临床的活动在天被估计 1, 3, 7 和 28。NOS 和支持 inflammatory cytokines 的粘膜存在被免疫组织化学和 RT-PCR 分析。结果:显著地显示的活跃 UC 和 CD 增加了直肠没有层次(10950 +/- 1280 每十亿分开的 7610 和 5040 +/-(ppb ) ,分别地) 作为与控制相比(154 +/- 71 ppb, P <
0.001 ) 。直肠不在 UC 和 CD 与疾病活动微弱地相关(r = 0.34 为 UC 和 r = 0.48 为 CD, P <
0.01 ) 。在 12 个病人,一堂类固醇倔强的功课导致了结肠切除术。仅仅稍微有的这些病人没增加层次(UC:620 +/- 270 ppb;CD:1260 +/- 550 ppb ) 与那些相比与治疗学的回答(UC:18860 +/- 530 ppb, P <
0.001;CD:10060 +/- 3200 ppb, P <
0.05 ) 。结论:直肠没有水平是在是的 IBD 的治疗反应的一个有用简历标记低没有层次预言差的临床的回答到类固醇治疗。 | Tryggve Ljung Sofie Lundberg Mark Varsanyi Catharina Johansson Peter T Schmidt Max Herulf Jon O Lundberg Per M Hellstr(o|¨)m | 2006 | World Journal of Gastroenterology2006，12，21： | 10 |
| 2 | Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation显示文摘BACKGROUND Arachidyl amido cholanoic acid(Aramchol)is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1)protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis.In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH),52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c,an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model[induced with a 0.1%methionine and choline deficient diet(0.1MCD)]after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20μmol/L Aramchol or vehicle for 48 h.Subsequently,analyses were performed including Western blot,proteomics by mass spectrometry,and fluxomic analysis with 13C-uniformly labeled glucose.For the in vivo part of the study,male C57BL/6J mice were randomly fed a control or 0.1MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk.Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in hepatocytes.This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA)synthesis and oxidation[PACCα/β(S79),SCD1,CPT1A/B,HADHA,and HADHB],oxidative phosphorylation(NDUFA9,NDUFB11,NDUFS1,NDUFV1,ETFDH,and UQCRC2),tricarboxylic acid(TCA)cycle(MDH2,SUCLA2,and SUCLG2),and ribosome(P-p70S6K[T389]and P-S6[S235/S236]).Flux experiments with 13Cuniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes,as indicated by the increase in the number of rounds that malate remained in the TCA cycle.Finally,liver metabolomic analysis showed that glucose homeostasis was improved by Aramchol in 0.1MCD fed mice in a dose-dependent manner,showing normalization of glucose,G6P,F6P,UDP-glucose,and Rbl5P/Xyl5P.CONCLUSION Aramchol exerts its effect on glucose and lipid metabolism in NASH through activation of AMPK and inhibition of mTORC1,which in turn activate FAβ-oxidation and oxidative phosphorylation. | David Fernández-Ramos Fernando Lopitz-Otsoa Laura Delacruz-Villar Jon Bilbao Martina Pagano Laura Mosca Maider Bizkarguenaga Marina Serrano-Macia Mikel Azkargorta Marta Iruarrizaga-Lejarreta Jesús Sot Darya Tsvirkun Sebastiaan Martijn van Liempd Felix M Goni Cristina Alonso María Luz Martínez-Chantar Felix Elortza Liat Hayardeny Shelly C Lu JoséM Mato | 2020 | World Journal of Gastroenterology2020，26，34： | 5 |
| 3 | 大堡礁和大峡谷世界遗产区的适应性管理显示文摘关于人类和环境相互关系的传统观念正在迅速改变。那种认为人类与自然是相互隔离的,自然资源是取之不尽用之不竭的,而且认为世界是稳定的、可以预测的并且是平衡的旧观点已经过时了。在动态的社会-生态景观中强调学习和灵活性管理为基础的适应性方法的新的理念框架已经迅速初现端倪。我们以两个典型的世界遗产地区(大堡礁和大峡谷)为案例来研究如何在自然资源管理中通过改善科学和社会两个方面的结合来指导多尺度管理系统的变革从而应对和处理人类越来越占据主导的世界中出现的不确定性、风险和变化。 | Terence P.Hughes Lance H.Gunderson Carl Folke Andrew H.Baird David Bellwood Fikret Berkes Beatrice Crona Ariella Helfgott Heather Leslie Jon Norberg Magnus Nystrm Per Olsson Henrik sterblom Marten Scheffer Heidi Schuttenberg Robert S.Steneck Maria Teng Max Troell Brian Walker James Wilson Boris Worm 丁莉 | 2007 | AMBIO-人类环境杂志2007，36，B11： | 4 |
| 4 | 选择性环氧化酶2抑制剂和传统非甾体抗炎药增加粥样血栓形成的风险吗?随机试验的荟萃分析显示文摘目的:评价选择性环氧化酶2(COX-2)抑制剂和传统的非甾体类抗炎药(NSMDs)在发生血管事件上的风险性。设计:对已发表和未发表随机试验的表格式资料进行荟萃分析,对传统 NSAIDs 的作用进行间接评估。资料来源:资料分别来源于 Medline 和 Embase(1966年1月至2005年4月);食品与药品管理局记录;以及诺华、辉瑞、默克公司的资料。回顾方法:符合以下条件的随机试验入组本研究:一种选择性 COX-2抑制剂与安慰剂比较或一种选择性 COX-2抑制剂与一种传统的 NSAID之间对比;用药持续时间至少4周;包含严重血管事件方面的信息,如心肌梗死、卒中或由于血管事件死亡。各个独立研究者和药厂为本研究提供了有关随机化的病人数目、血管事件的数目以及每个随机化小组中随访的人时(Person time)等信息。结果:在与安慰剂对比的试验中,选择性COX-2抑制剂使严重血管事件发生率增加42%(1.2%/年比0.9%/年;率比1.42,95%可信区间1.13~1.78;P=0.005);不同的选择性 COX-2抑制剂之间没有显著性差异。这主要归因于心肌梗死的风险增加(0.6%/年比0.3%/年;1.86,1.33~2.59;P=0.0003),在其他血管性事件上没有明显的区别。在为时至少1年的试验中(平均2.7年),血管事件的率比是1.45(1.12~1.89;P=0.005)。总的来说,严重血管事件的发生率在选择性 COX-2抑制剂和任何传统 NSAID 之间没有差异(1.0%/年比0.9%/年;1.16,0.97~1.38;P=0.1)。然而,在选择性 COX-2抑制剂与萘普生对比的试验(1.57,1.21~2.03)和选择性COX-2抑制剂与非萘普生类 NSAIDs 相比较的试验之间(0.88,O.69~1.12),我们发现了统计学差异。与安慰剂比较血管事件的总体比率如下:萘普生0.92(0.67~1.26),布洛芬1.51(0.96~2.37),双氯芬酸1.63(1.12~2.37)。结论:选择性 COX-2抑制剂可以中等度增加血管事件的风险性,大剂量布洛芬和双氯芬酸同样具有此作用,但大剂量萘普生不明显增加血管事件的风险性。 | Patricia M Kearney Colin Baigent Jon Godwin Heather Halls Jonathan R Emberson Carlo Patrono 徐东(译) 张卓莉(校) | 2006 | 英国医学杂志中文版2006，9，5： | 4 |
| 5 | Heparin resistance in severe thermal injury:a prospective cohort study显示文摘Background:Low molecular-weight heparin(LMWH)is routinely administered to burn patients for thromboprophylaxis.Some studies have reported heparin resistance,yet the mechanism(s)and prevalence have not been systematically studied.We hypothesized that nucleosomes,composed of histone structures with associated DNA released from injured tissue and activated immune cells in the form of neutrophil extracellular traps(NETs or NETosis),neutralize LMWH resulting in suboptimal anticoagulation,assessed by reduction in anti-factor Xa activity.Methods:Blood was sampled from>15%total body surface area(TBSA)burn patients receiving LMWH on days 5,10 and 14.Peak anti-factor Xa(AFXa)activity,anti-thrombin(ATIII)activity,cellfree DNA(cfDNA)levels and nucleosome levels were measured.Mixed effects regression was adjusted for multiple confounders,including injury severity and ATIII activity,and was used to test the association between nucleosomes and AFXa.Results:A total of 30 patients with severe burns were included.Mean TBSA 43%(SD 17).Twentythree(77%)patients were affected by heparin resistance(defined by AFXa activity<0.2 IU/mL).Mean peak AFXa activity across samples was 0.18 IU/mL(SD 0.11).Mean ATIII was 81.9%activity(SD 20.4).Samples taken at higher LWMH doses were found to have significantly increased AFXa activity,though the effect was not observed at all doses,at 8000 IU no samples were heparin resistant.Nucleosome levels were negatively correlated with AFXa(r=−0.29,p=0.050)consistent with the hypothesis.The final model,with peak AFXa as the response variable,was adjusted for nucleosome levels(p=0.0453),ATIII activity(p=0.0053),LMWH dose pre-sample(p=0.0049),drug given(enoxaparin or tinzaparin)(p=0.03),and other confounders including severity of injury,age,gender,time point of sample.Conclusions:Heparin resistance is a prevalent issue in severe burns.Nucleosome levels were increased post-burn,and showed an inverse association with AFXa consistent with the hypothesis that they may interfere with the anticoagulant effect of heparin in vivo and contribute to heparin resistance.Accurate monitoring of AFXa activity with appropriate therapy escalation plans are recommended with dose adjustment following severe burn injury. | Liam D Cato Benjamin Bailiff Joshua Price Christos Ermogeneous Jon Hazeldine William Lester Gillian Lowe Christopher Wearn Jonathan RB Bishop Janet M Lord Naiem Moiemen Paul Harrison | 2021 | Burns & Trauma2021，9，1： | 3 |
| 6 | The potential drivers in forming avian biodiversity hotspots in the East Himalaya Mountains of Southwest China显示文摘Little has been published to describe or interpret Asian biodiversity hotspots,including those in the East Himalayan Mountains of Southwest China(HMSC),thus making necessary a review of the current knowledge.The Pliocene and Pleistocene geological and glacial histories of the Asian continent differ from those of Europe and North America,suggesting different mechanisms of speciation and extinction,and,thus,different responses to climate changes during the Quaternary glaciations.This short review summarizes potential drivers in shaping and maintaining high species richness and endemism of birds in the HMSC.The geographical location at the junction of different biogeographical realms,the wide range of habitats and climates along the extensive elevational range,the complex topography and the distinct geological history of this region have probably contributed to the evolution of an exceptionally species-rich and endemic-rich,specialized montane avian fauna.The Mountain systems in the HMSC may have provided refugia where species survived during the glacial periods and barriers for preventing species dispersal after the glacial periods.More studies are required to further test this refugia hypothesis by comparing more cold-tolerent and warm-tolerent species. | Fumin LEI Yanhua QU Gang SONG Per ALSTRÖM Jon FJELDSÅ | 2015 | Integrative Zoology2015，10，2： | 3 |
| 7 | Improved biomass productivity and water use efficiency under water deficit conditions in transgenic wheat constitutively expressing the barley HVA 1 gene显示文摘 | Elumalai Sivamani Ahmed Bahieldin Jon M Wraith Thamir Al-Niemi William E Dyer Tuan-Hua David Ho Rongda Qu | 2000 | Plant Science2000，，1： | 2 |
| 8 | Ankle Fractures in the Elderly: What You Get Depends on Where You Live and Who You See显示文摘 | Kenneth J Koval Jon Lurie Weiping Zhou Michael B Sparks Robert V Cantu Scott M Sporer James Weinstein | 2005 | Journal of Orthopaedic Trauma2005，，9： | 2 |
| 9 | Improved biomass productivity and water use efficiency under water deficit conditions in transgenic wheat constitutively expressing the barley HVA 1 gene显示文摘 | Elumalai Sivamani Ahmed Bahieldin Jon M Wraith Thamir Al-Niemi William E Dyer Tuan-Hua David Ho Rongda Qu | 2000 | Plant Science2000，，1： | 2 |
| 10 | Targeting Dexamethasone to Macrophages in a Porcine Endotoxemic Model显示文摘 | Asger Granfeldt Christine Lodberg Hvas Jonas Heilskov Graversen Peter Astrup Christensen Mikkel Due Petersen Gabriela Anton Pia Svendsen Christoffer S?lling Anders Etzerodt Else T?nnesen S?ren Kragh Moestrup Holger Jon M?ller | 2013 | Critical Care Medicine2013，，11： | 2 |
| 11 | Ribosomally synthesized antimicrobial peptides : their function, structure, biogenesis and mechanism of action 显示文摘 | Jon N M Ingolf F N | 1997 | Arch Microbiol1997，167，： | 1 |
| 12 | Biochemical and immunologic mechanisms in atopic dermatitis:New targets for imerging therapies显示文摘 | Hanifin MD Chan S | 1999 | J Am Acad Dermatol1999，41，： | 1 |
| 13 | Curcumin disrupts mitotic spindle structure and induces micronucleation in MCF-7 breast cancer cells 显示文摘 | Jon M Holy j M | 2002 | Mut Res2002，518，1： | 1 |
| 14 | Two-stage and multi-splitting methods for the parallel solution of lienar system显示文摘 | SZYLD D B JONS M T | 1992 | SIAM J Matrix Annl Appl1992，13，2： | 1 |
| 15 | Natural fractures in the Barnett shale and their importance for hydraulic fracture treatments显示文摘 | Julia F W G Reed R M Holder Jon | 2007 | AAPG2007，91，4： | 1 |
| 16 | Alginate hydrogels as synthetic extraeellular matrix materials 显示文摘 | Jon A R Gerard M Mooney D J | 1999 | Biomaterials1999，20，： | 1 |
| 17 | Application oftransient infrared and near infrared spectroscopy totransition metal complex excited states and inter-mediates显示文摘 | Jennifer M B Michael W G Jon R S | 2007 | Coord Chem Rev2007，251，： | 1 |
| 18 | An experimental investigation of the electrostatic discharge (ESD) mechanism in packaged semiconductor devices显示文摘 | M C Jon T L Welsher | 1994 | J of Electrostatics1994，32，： | 1 |
| 19 | Biological activity of cryopreserved bovine spermatogonial stem cells during in vitro culture显示文摘 | Jon M O Jerry J R Derek J M | 2004 | Biology of Reproduction2004，71，： | 1 |
| 20 | 显示文摘 | Jon A R Gerard M | 1999 | Biomaterials1999，20，： | 1 |
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