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钠-葡萄糖共转运蛋白-2抑制剂或胰高血糖素样肽-1受体激动剂治疗成人2型糖尿病:临床实践指南

英国医学杂志中文版 2021年第9期24卷 523-531页

作者： Sheyu Li Per olav Vandvik Lyubov Lytvyn Gordon H Guyatt Suetonia C Palmer Rene Rodriguez-Gutierrez Farid Foroutan Thomas Agoritsas Reed A C Siemieniuk Michael Walsh Lawrie Frere David J Tunnicliffe Evi V Nagler Veena Manja bjφrn olav asvold Vivekanand Jha Mieke Vermandere Karim Gariani Qian Zhao Yan Ren Emma Jane Cartwright Patrick Gee Alan Wickes Linda Fems Robin Wright Ling Li Qiukui Hao Reem A Mustafa 无郭鹤鸣(译) Chengdu China Chinese Evidencebased Medicine Center Cochrane China Center and MAGIC China CenterWest China HospitalSichuan UniversityChengduChina University of Oslo OsloNorway MAGIC Evidence Ecosystem Foundation Department of Health Research Methods Evidence and ImpactMcMaster UniversityHamiltonONCanada Department of Medicine McMaster UniversityHamiltonONCanada Department of Medicine University of OtagoChristchurchNew Zealand Plataforma INVEST Medicina UANL-KER Unit(KER Unit Mexico) Subdireccion de InvestigacionUniversidad Autonoma de Nuevo LeonMonterrey64460Mexico Knowledge and Evaluation Research Endocrinology Mayo ClinicRochesterMN55905USA Endocrinology Division Department of Internal MedicineUniversity Hospital"Dr.Jose E.Gonzalez"Universidad Autonoma de Nuevo LeonMonterrey64460Mexico Ted Rogers Center for Heart Research Canada Service of Endocrinology DiabetesNutrition and Patient Therapeutic EducationGeneva University HospitalsGenevaSwitzerland Newbridge Surgery BathUK Sydney School of Public Health The University of SydneySydneyAustralia Centre for Kidney Research The Children's Hospital at WestmeadSydneyAustralia Renal Division Ghent University HospitalBelgium University of California Davis USA Department of Endocrinology Clinic of MedicineSt Olavs HospitalTrondheim University HospitalTrondheimNorway K.G.Jebsen Center for Genetic Epidemiology Department of Public Health and NursingNTNUNorwegian University of Science and TechnologyTrondheimNorway The George Institute for Global Health UNSWIndia School of Public Health Imperial CollegeLondonUK Prasanna School of Public Health Manipal Academy of Higher EducationManipalIndia Department of Public Health and Primary Care KU LeuvenLeuvenBelgium International Medical Center/Ward of General Practice West China HospitalSichuan UniversityChengduChina London UK Founder&CEHD iAdvorateInc.VirginiaPatient partner Patient partner The Center of Gerontology and Geriatrics/National Clinical Research Center for Geriatr

临床问题对于存在不同心血管风险及肾脏结局的2型糖尿病患者,在原有生活方式干预和/或其他降糖药物的基础上加用钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂的获益及风险是什么?现行做法几十年来,2型糖尿病... 详细信息

临床问题对于存在不同心血管风险及肾脏结局的2型糖尿病患者,在原有生活方式干预和/或其他降糖药物的基础上加用钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂的获益及风险是什么?现行做法几十年来,2型糖尿病的治疗决策都以控制血糖为主导。SGLT-2抑制剂和GLP-1受体激动剂在传统观念中常被用于二甲双胍治疗后血糖仍控制不佳的患者。目前这一现状已经发生了改变,这得益于多项临床研究结果。研究显示SGLT-2抑制剂和GLP-1受体激动剂拥有独立于药物降糖作用之外的对于动脉粥样硬化性心血管病(CVD)和慢性肾脏病(CKD)的获益。建议本指南阐述了针对不同风险分层的成人2型糖尿病患者使用SGLT-2抑制剂或GLP-1受体激动剂的建议。•伴有3种或更少的心血管风险因素且不存在CVD或CKD:不建议启动SGLT-2抑制剂或GLP-1受体激动剂治疗。(推荐等级:弱)•伴有3种以上心血管风险因素且不存在CVD或CKD:建议启动SGLT-2抑制剂治疗,不建议启动GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD或CKD:建议启动SGLT-2抑制剂治疗和GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD和CKD:建议启动SGLT-2抑制剂治疗(推荐等级:强)和GLP-1受体激动剂治疗。(推荐等级:弱)•对于那些想要进一步降低CVD和CKD结局风险的患者:推荐优先启用SGLT-2抑制剂治疗而非GLP-1受体激动剂治疗。(推荐等级:弱)这项指南是如何制订的一个由患者、临床医生和方法学家共同组成的国际小组提出了这些推荐意见。这些推荐意见基于可信度较高的指南的标准,并使用GRADE分级方法进行评估。该小组采用了息者个体化的观点。证据一项关于获益与风险的系统综述和网络meta分析(764项随机对照研究,包括421346例参与者)发现SGLT-2抑制剂和GLP-1受体激动剂可以降低总体死亡率、心肌梗死发生率、终末期肾病或肾衰竭的发生率(中等至高等质量的证据)。在不同的亚组中这些药物对卒中、因心力衰竭所致住院和其他主要不良事件有不同的影响。药物绝对获益的程度因患者个体风险的不同有很大的差异。(例如,对于接受了超过5年药物治疗的1000例患者,在最低风险人群中死亡人数减少了5人,在最高风险人群中死亡人数减少了48人)。一项关于预后的综述确认了14种风险预测模型,其中一种(RECODe)在证据总结中报告了大部分基线风险评估数据,小组利用该模型以支持风险分层的建议。考虑到患者的价值观及个体差异,指南推荐的支撑证据包括一项对已发表论文的系统综述、一项患者焦点小组研究、一项临床问题总结,以及一项指南调查。指南解读我们依据不同的CVD和CKD风险水平,综合考虑获益、风险和其他因素的平衡,以及每一个风险组别的实际问题,来对推荐意见进行分层。本指南强烈建议CVD和CKD患者使用SGLT-2抑制剂治疗,这说明专家组认为其具有显著的获益。而对于其他成人2型糖尿病患者,推荐等级较弱,这说明专家组想要在获益、风险及治疗花费上取得一个更好的平衡。临床医生通过该指南可以使用可靠的风险计算模型,如RECODe,来明确其患者的个体心血管和肾脏疾病风险。医患交互式总结临床证据和制订决策有助于患者知晓治疗选择,包括进行共同决策。2型糖尿病人群(全球患病率不断增长1-2)正面临着不断增加的心血管疾病、肾脏病和其他并发症的风险3。数十年来,2型糖尿病的管理始终以控制血糖及糖化血红蛋白(HbA1c)为治疗目标4-5,但是,最近的高质量随机对照研究已经对这种以血糖为中心的治疗模式发起了挑战。研究结果显示,强化血糖控制未必会降低大血管不良事件,它还可能带来不利影响监管机构现在要求新型糖尿病药物必须证明其具有心血管和肾脏获益才能获得批准。对两类新药--钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂(见框图1)的临床试验结果显示,在现有治疗方案(常规治疗)之上加用这些药物,对死亡、心肌梗死、卒中、心力衰竭和肾脏的结局(如进展为终末期肾病)都有获益8-12。

关键词：胰高血糖素样肽1 终末期肾病临床研究结果心血管风险 meta分析临床试验结果临床证据控制血糖

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Single and multiple stressor effect of road deicers and Cu on Atlantic salmon (Salmo salar) alevins from hatching till swim-up

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Journal of Environmental Sciences 2018年第4期30卷 368-378页

作者： Urma Mahrosh bjФrn olav Rosseland Brit Salbu Hans-Christian Teien Nortuegian Uniuersity of Life Sciences Department of Environmental Sciences N-1432 As Norway National University of Sciences and Technology H-12 Islamabad Pakistan Norwegian University of Life Sciences Department of Ecology and Natural Resource Management N-1432 As Norway

Road salts are frequently used for deicing of roads in the Nordic countries. During snow-melt, the road run-off containing high concentrations of road salt and various metals such as Cu remobilized from sand, silt and dust may negatively influence organisms in downstream receiving water bodies. The present work focuses on the impact of road salt（NaCl） and Cu, separately and in mixtures on Atlantic salmon alevins from hatching till swim-up. The results showed that high road salt concentrations could induce a series of negative effects in alevins such as reduced growth, deformities, delayed swim-up and mortality. For alevins exposed to all tested road salt concentrations（100–1000 mg/L）,mortality was significantly higher compared to control. In exposure to Cu solutions（5–20 μg Cu/L）, no effects on growth, morphology, swim-up or mortality of alevins compared to control were observed. In mixture solutions（road salt and Cu）, ultrafiltration of the exposure water demonstrated that only 20%–40% of Cu was present as positively charged low molecular mass（LMM） Cu species assumed to be bioavailable. When exposed to road salt and Cu mixtures, negative effects in alevins such as reduced growth, deformities,delayed swim-up and mortality were observed. The overall results indicated that the road salt application could seriously affect sensitive life stages of Atlantic salmon, and application of road salt should be avoided during the late winter–early spring period.

关键词： Road deicers Copper Atlantic salmon Alevins Biological effects

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Experimental Investigation on the Vapor Chambers with Sintered Copper Powder Wick

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Journal of Thermal Science 2021年第6期30卷 1938-1950页

作者： HUANG Dou JIA Li WU Hong AAKER olav Beijing Key Laboratory of Flow and Heat Transfer of Phase Changing in Micro and Small Scale School of MechanicalElectronic and Control EngineeringBeijing Jiaotong UniversityBeijing 100044China Faculty of Engineering 0stfold University CollegeBox700N-1757Norway

High power electronics units generate high-density heat flux,which poses a significant threat to the reliability of these *** vapor chamber(VC)has a very high heat transfer rate and has a wide range of applications in the heat dissipation of electronic *** with sintered copper powder wicks sized as irregular shape copper powder 50μm(I-50μm),I-75μm,I-110μm,I-150μm were studied in this *** effect of liquid filling ratio was *** results indicated that the thermal resistance of all VCs decreased with the increase of heating *** capillary performance of wick was the dominant factor for the heat transfer performance of VCs with different kinds of wick.A capillary performance factor was proposed to evaluate the capillary performance of *** capillary performance factor of VC with the wick of I-75μm was much higher than that of the other types of VC in this *** heat source surface temperature of VCs could be affected by filling ratio and wick ***,it should be insensitive to the filling ratio when a better capillary performance factor was *** the same heating area and similar structure,the maximum heat flux density of the VC would decrease as the height of vapor cavity decreased.

关键词： vapor chamber copper powder capillary performance heat transfer performance thermal resistance

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Structure and evolution of the continental margin off Norway and the Barents Sea

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Episodes 2008年第1期31卷 82-91页

作者： Jan Inge Faleide Filippos Tsikalas AsbjФrn Breivik Rolf Mjelde Oliver Ritzmann Фyvind Engen Jonas Wilson olav Eldholm Department of Geosciences University of Oslo P.O. Box 1047 Blindem N-0316 Oslo Norway. Department of Earth Science University of Bergen Allegaten 41 N-5007 Bergen Norway. Present address： Eni Norge AS P.O. Box 101 Forus N-4064 Stavanger Norway. Present address： StatoilHydro N-0246 Oslo Norway.

The Norwegian Margin formed in response to early Cenozoic continental breakup and subsequent opening of the Norwegian-Greenland Sea. There is a well-defined margin segmentation and the various segments are characterized by distinct crustal properties, structural and magmatic styles, and post-opening history of vertical motions. The sedimentary basins at the conjugate continental margins off Norway and Greenland and in the western Barents Sea developed as a result of a series of post-Caledonian rift episodes until early Cenozoic time, when complete continental separation took place.

关键词：大陆边界地质构造巴伦支海挪威

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Connective tissue growth factor reacts as an IL-6/STAT3-regulated hepatic negative acute phase protein

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World Journal of Gastroenterology 2011年第2期17卷 151-163页

作者： olav A Gressner Ieva Peredniene Axel M Gressner Institute of Clinical Chemistry and Pathobiochemistry Central LaboratoryRWTH-University Hospital Wisplinghoff Medical Laboratories Classen-Kappelmann-Str.2450931 CologneGermany Synlab Lab Services Gubener Str.3986156 AugsburgGermany

AIM:To investigate the mechanisms involved in a possible modulator role of interleukin(IL) -6 signalling on CYR61-CTGF-NOV(CCN) 2/connective tissue growth factor(CTGF) expression in hepatocytes(PC) and to look for a relation between serum concentrations of these two parameters in patients with acute inflammation. METHODS:Expression of CCN2/CTGF,p-STAT3,p-Smad 3/1 and p-Smad2 was examined in primary freshly isolated rat or cryo-preserved human PC exposed to various stimuli by Western blotting,electrophoretic mobility shift assay(EMSA) ,reporter-gene-assays and reversetranscriptase polymerase chain reaction. RESULTS:IL-6 strongly down-regulated CCN2/CTGF protein and mrnA expression in PC,enhanceable by extracellular presence of the soluble IL-6 receptor gp80,and supported by an inverse relation between IL-6 and CCN2/CTGF concentrations in patients'*** inhi-bition of TGFβ1 driven CCN2/CTGF expression by IL-6 did not involve a modulation of Smad2(and Smad1/3) ***,the STAT3 SH2 domain binding peptide,a selective inhibitor of STAT3 DNA binding activity,counteracted the inhibitory effect of IL-6 on CCN2/CTGF expression much more pronounced than pyrrolidine-dithiocarbamate,an inhibitor primarily of STAT3 *** EMSA confirmed STAT3 binding to the proposed proximal STAT binding site in the CCN2/CTGF promoter. CONCLUSION:CCN2/CTGF is identified as a hepatocellular negative acute phase protein which is downregulated by IL-6 via the STAT3 pathway through interaction on the DNA binding level.

关键词：结缔组织生长因子聚合酶链反应急性期蛋白肝细胞 DNA结合活性 STAT3 选择性抑制剂 Smad2

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Forest pasturing of livestock in Norway: effects on spruce regeneration

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Journal of Forestry Research 2014年第4期25卷 941-945页

作者： olav Hjeljord Trond Hist?l Hilde Karine Wam Norwegian University of Life Sciences Department of Ecology and Natural Resource Management Box 5003 1432 ?s Norway Norwegian Institute for Agricultural and Environmental Research Organic Food and Farming Division Gunnarsveg 6 6630 Tingvoll Norway

Forest pasturing of free-roaming livestock is a common prac- tice in many parts of the world, but knowledge on how it affects tree regeneration in boreal forests is lacking. We mapped tree density, live- stock site use and accumulated damage to young trees of commercial interest （Norway spruce, Picea abies L. Karst.） on 56 clearcuts inside and outside a fenced forest area used for livestock pasturing in Ringsaker, Norway. Inside the fence 56-1.8% of spruce trees were damaged com- pared to 37-3.4% outside. Proportion of damaged spruce trees was posi- tively related to cattle use of the clearcut, but not so for sheep. On the most intensively used clearcuts, four out of five trees were damaged. The density of deciduous trees was five times lower inside compared to out- side of the fence （varying with plant species）. While livestock grazing may reduce resource competition in favour of spruce, the current animal density clearly is impeding forest regeneration in the study area.

关键词： browsing cattle damage timber sheep ungulate

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Non-invasive biomarkers for monitoring the fibrogenic process in liver:A short survey

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World Journal of Gastroenterology 2009年第20期15卷 2433-2440页

作者： Axel M Gressner Chun-Fang Gao olav A Gressner Institute of Clinical Chemistry and Pathobiochemistry Central Laboratory RWTH- University Hospital Aachen Pauwelsstr. 30 52074 Aachen Germany Department of Laboratory Medicine Eastern Hepatobiliary Hospital Second Military Medical University 225 Shanghai Road Shanghai 200438 China

The clinical course ofchronic liver diseases is significantly dependent on the progression rate and the extent offibrosis, i.e. the non-structured replacement of necrotic parenchyma by extracellular matrix. Fibrogenesis, i.e. the development offibrosis can be regarded as an unlimited wound healing process, which is based on matrix (connective tissue) synthesis in activated hepatic stellate cells, fibroblasts (fibrocytes), hepatocytes and biliary epithelial cells, which are converted to matrix-producing (myo-)fibroblasts by a process defined as epithelial-mesenchymal transition. Blood (noninvasive) biomarkers offibrogenesis and fibrosis can be divided into class and class analytes. Class biomarkers are those single tests, which are based on the pathophysiology offibrosis, whereas class biomarkers aremostly multiparametric algorithms, which have been statistically evaluated with regard to the detection and activity ofongoing fibrosis. Currently available markers fulfil the criteria ofideal clinical-chemical tests only partially, but increased understanding ofthe complex pathogenesis offibrosis offers additional ways for pathophysiologically well based serum (plasma) biomarkers. They include TGF-β-driven marker proteins, bone marrow-derived cells (fibrocytes), and cytokines, which govern proand anti-fibrotic activities. Proteomic and glycomic approaches ofserum are under investigation to set up specific protein or carbohydrate profiles in patients with liver fibrosis. These and other novel parameters will supplement or eventually replaceliver biopsy/histology, high resolution imaging analysis, and elastography for the detection and monitoring of patients at risk ofdeveloping liver fibrosis.

关键词：生物标志物肝纤维化侵入性进程监测

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3D non-isothermal phase-field simulation of microstructure evolution during selective laser sintering

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npj Computational Materials 2019年第1期5卷 442-453页

作者： Yangyiwei Yang olav Ragnvaldsen Yang Bai Min Yi Bai-Xiang Xu Mechanics of Functional Materials Division Institute of Materials ScienceTechnische Universität Darmstadt64287 DarmstadtGermany Department of Materials Science and Engineering Norwegian University of Science and Technology7491 TrondheimNorway State Key Laboratory of Mechanics and Control of Mechanical Structures&Key Laboratory for Intelligent Nano Materials and Devices of Ministry of Education&College of Aerospace Engineering Nanjing University of Aeronautics and Astronautics(NUAA)210016 NanjingChina

During selective laser sintering(SLS),the microstructure evolution and local temperature variation interact *** of conventional isothermal sintering model is thereby insufficient to describe *** this work,we construct our model from entropy level,and derive the non-isothermal kinetics for order parameters along with the heat transfer equation coupled with microstructure *** from partial melting and laser-powder interaction are also *** then perform 3D finite element non-isothermal phase-field simulations of the SLS single *** confront the high computation cost,we propose a novel algorithm analogy to minimum coloring problem and manage to simulate a system of 200 grains with grain tracking algorithm using as low as 8 non-conserved order ***,applying the model to SLS of the stainless steel 316L powder,we identify the influences of laser power and scan speed on microstructural features,including the porosity,surface morphology,temperature profile,grain geometry,and *** further validate the first-order kinetics of the transient porosity during densification,and demonstrate the applicability of the developed model in predicting the linkage of densification factor to the specific energy input during SLS.

关键词： microstructure isothermal kinetics

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The oral commensal Streptococcus mitis activates the aryl hydrocarbon receptor in human oral epithelial cells

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International Journal of Oral Science 2017年第3期9卷 145-150页

作者： stian a engen gro h rørvik olav schreurs inger js blix karl schenck department of oral biology faculty of dentistryuniversity of osloOsloNorway institute of clinical dentistry faculty of dentistryuniversity of osloOsloNorway

Streptococcus mitis （S. mitis） is a pioneer commensal bacterial species colonizing many of the surfaces of the oral cavity in healthy individuals. Yet, not much information is available regarding its interaction with the host. We used examination of its transcriptional regulation in oral keratinocytes to elucidate some of its potential roles in the oral cavity. Transcription factor analysis of oral keratinocytes predicted S. *** activation of aryl hydrocarbon receptor （AhR）, Activation and functionality of AhR was confirmed through nuclear translocation determined by immunofluorescence microscopy and real-time polymerase chain reaction with reverse transcription analysis of CYPIA1, the hallmark gene for AhR activation. Addition of Streptococcus mutans or Streptococcus gordonfi did not induce CYPIA1 transcription in the keratinocyte cultures. Introduction of an AhR-specific inhibitor revealed that S. mitis-mediated transcription of CXCL2 and CXCL8 was regulated by AhR. Elevated levels of pmstaglandin E2 （enzyme-linked immunosorbent assay） in supernatants from S. mitis-treated oral epithelial cells were also attenuated by inhibition of AhR activity. The observed AhR-regulated activities point to a contribution of S. mitis in the regulation of inflammatory responses and thereby to wound healing in the oral cavity. The concept that the oral commensal microbiota can induce AhR activation is important, also in view of the role that AhR has in modulation of T-cell differentiation and as an anti-inflammatory factor in macrophaees.

关键词： aryl hydrocarbon receptor commensal inflammation oral epithelium prostaglandin E2 Streptococcus

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Imaging for Minimally Invasive Surgery

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Surgical Science 2016年第8期7卷 333-341页

作者： Jan Gunnar Skogås Hans olav Myhre Asbjørn Ødegård Gabriel Kiss Operating Rooms of the Future St. Olavs Hospital University Hospital of Trondheim and the Norwegian University of Science and Technology Trondheim Norway Clinic of Radiology and Nuclear Medicine St. Olavs University Hospital Trondheim Norway

The successful outcome of any minimally invasive procedure is highly dependent on the imaging chain, as the medical team has to rely on indirect visualization of the surgical field during the entire procedure. During the last decade, the quality of the images obtainable pre- and intraoperatively has evolved significantly. In addition to the introduction of intra-operative image acquisition techniques such as ultrasound, X-ray, CT or MR, optical imaging technology as well as the corresponding processing units have undergone a rapid development. The article will review the activity related to minimally invasive procedures at the Operating Rooms of the Future (FOR) at St. olavs Hospital, University Hospital of Trondheim, Norway. The imaging related demands of several surgical fields are introduced and the evolution of the imaging and visualization techniques at FOR will be presented. Subsequently, ongoing research projects in a dedicated visualization laboratory will be discussed and the advantages of updating the imaging equipment continuously in order to keep up with the latest developments in the field will be presented. It will be shown that the quality of the image acquisition and display can be significantly improved when compared to today’s standard. In addition to increasing the surgeon’s confidence, better imaging will lead to increased patient safety as well as more efficient interventions.

关键词： Minimally Invasive Surgery Medical Imaging and Visualization Operating Room of the Future

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