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| 1 | 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:临床实践指南显示文摘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。 | 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) | 2021 | 英国医学杂志中文版2021，24，9： | 7 |
| 2 | SIRT3-mediated inhibition of FOS through histone H3 deacetylation prevents cardiac fibrosis and inflammation显示文摘Sirtuin 3(SIRT3)is a deacetylase that modulates proteins that control metabolism and protects against oxidative stress.Modulation of SIRT3 activity has been proposed as a promising therapeutic target for ameliorating metabolic diseases and associated cardiac disturbances.In this study,we investigated the role of SIRT3 in inflammation and fibrosis in the heart using male mice with constitutive and systemic deletion of SIRT3 and human cardiac AC16 cells.SIRT3 knockout mice showed cardiac fibrosis and inflammation that was characterized by augmented transcriptional activity of AP-1.Consistent with this,SIRT3 overexpression in human and neonatal rat cardiomyocytes partially prevented the inflammatory and profibrotic response induced by TNF-α.Notably,these effects were associated with a decrease in the mRNA and protein levels of FOS and the DNA-binding activity of AP-1.Finally,we demonstrated that SIRT3 inhibits FOS transcription through specific histone H3 lysine K27 deacetylation at its promoter.These findings highlight an important function of SIRT3 in mediating the often intricate profibrotic and proinflammatory responses of cardiac cells through the modulation of the FOS/AP-1 pathway.Since fibrosis and inflammation are crucial in the progression of cardiac hypertrophy,heart failure,and diabetic cardiomyopathy,our results point to SIRT3 as a potential target for treating these diseases. | Xavier Palomer MSilvia Román-Azcona Javier Pizarro-Delgado Ana Planavila Francesc Villarroya Brenda Valenzuela-Alcaraz Fátima Crispi Álvaro Sepúlveda-Martínez Irene Miguel-Escalada Jorge Ferrer JFrancisco Nistal Raquel García Mercy MDavidson Emma Barroso Manuel Vázquez-Carrera | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 7 |
| 3 | The Treatment-Naive Microbiome in New-Onset Crohn’s Disease显示文摘 | Dirk Gevers Subra Kugathasan Lee A. Denson Yoshiki Vázquez-Baeza Will Van Treuren Boyu Ren Emma Schwager Dan Knights Se Jin Song Moran Yassour Xochitl C. Morgan Aleksandar D. Kostic Chengwei Luo Antonio González Daniel McDonald Yael Haberman Thomas Walter | 2014 | Cell Host & Microbe2014，，： | 3 |
| 4 | The ozone paradox: ozone Is a strong oxidant aswell as a medical drug显示文摘 | Bocci V Emma B Valter TG | 2009 | Med Res Rev2009，29，4： | 1 |
| 5 | The use of willingness-to-pay approaches in mammal conservation显示文摘 | Alison C Emma J V H | 2001 | Mammal Bev2001，31，2： | 1 |
| 6 | Utility of l-methylcyclopropene as a papaya postharvest treatment显示文摘 | Ashariya Manenoi Emma Ruth V Bayogan Siwaporn Thumdee | 2007 | Postharvest Biology and Technology2007，44，1： | 1 |
| 7 | Automated Singal Generation in Prescription-Event Monitoring显示文摘 | Emma Heeley Lynda V Wilton Sead A W Shakir | 2008 | Drug Safety2008，25，6： | 1 |
| 8 | TG/MS, Py-GC/MS and THM-GC/MS study of the composition and thermal behavior of extraetive components of Robinia pseudoacacia显示文摘 | ERIKA M EMMA J GABOR V | 2007 | Journal of Analytical and Applied Pyrolysis2007，79，： | 1 |
| 9 | Application of ultrahigh-pressure liquid chromatography–tandem mass spectrometryto the determination of multi-class pesticides in environmentaland wastewater samples Study of matrix effects显示文摘 | José M M Emma G L Juan V S | 2009 | Journal ofChromatography A2009，1216，14： | 1 |
| 10 | Development of a model to select plants with optimum metal phytoextration potential显示文摘 | Sebasti6n D G Flora A V Emma F C | 2011 | Environmental Science and Pollution Research2011，18，6： | 1 |
| 11 | Antioxidative action of the ethanolic extract and some hydroxycoumarins of Fraxinus ornus bark显示文摘 | EMMA M M NEDJALKA V I Y IVANKA N K | 1994 | Food Chemistry1994，51，2： | 1 |
| 12 | Regulation of K-Cl cotransport by protein phosphatase 1alpha in mouse erythrocytes显示文摘 | EMMA V M ANDREA B | 2006 | Pflugers Arch2006，451，6： | 1 |
| 13 | Recovery of meiofauna communities following mudflat disturbance by tramp- ling associated with crab-tiling 显示文摘 | GARETH E L J MARTIN J A EMMA V S | 2007 | Marine Environmental Re- search2007，64，4： | 1 |
| 14 | Automated Singal Generation in Prescription-Event Monitoring显示文摘 | Emma Heeley Lynda V Wilton Sead A W Shakir | 2002 | Drug Safety2002，，： | 1 |
| 15 | CD25-regulatory T cells and tumor immunity显示文摘 | Emma J Michaela D V Denise G | 2003 | Immunol Lett2003，85，2： | 1 |
| 16 | Physico chemical characterization and stability of inulin gels 显示文摘 | Emma C Elena V Claudio C | 2007 | European Food Research and Technology2007，225，1： | 1 |
| 17 | Acyclic diterpenes from perymenlum hintonii显示文摘 | Emma M Marisela B Jose L V | 1998 | Phytochemistry1998，49，4： | 1 |
| 18 | DNA Binding Studies and Site Selective Fluorescence Sensitization of an Anthryl Probe显示文摘 | Kumar C V Emma H Asuncion | 1993 | JAm Chem Soc1993，115，： | 1 |
| 19 | Enhancement of the citrus immune system provides effective resistance against Ahemaria brown spot disease 显示文摘 | Eugenio L Emma F C Begonya V | 2013 | Journal of Plant Physiology2013，170，： | 1 |
| 20 | Non-invasive Ventilation in an Elderly Population Admitted to a Respiratory Monitoring Unit: Causes, Complications and One-year Evolution显示文摘 | Gonzalo Segrelles Calvo Enrique Zamora García Rosa Girón Moreno Emma Vázquez Espinosa Rosa Mar Gómez Punter Gilda Fernandes Vasconcelos Claudia Valenzuela Julio Ancochea Bermúdez | 2012 | Archivos de Bronconeumología (Internet)2012，，10： | 1 |
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