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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 | Three-dimensional perfused human in vitro model of nonalcoholic fatty liver disease显示文摘AIM To develop a human in vitro model of non-alcoholic fatty liver disease(NAFLD), utilising primary hepatocytes cultured in a three-dimensional(3D) perfused platform. METHODS Fat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids(FFA) from culture medium was monitored. Hepatic functions, gene expression profiles and adipokine release were compared for cells cultured in fat and lean conditions. To determine if fat loading in the system could be modulated hepatocytes were treated with known anti-steatotic compounds. RESULTS Hepatocytes cultured in fat medium were found to accumulate three times more fat than lean cells and fat uptake was continuous over a 14-d culture. Fat loading of hepatocytes did not cause any hepatotoxicity and significantly increased albumin production. Numerous adipokines were expressed by fatty cells and genes associated with NAFLD and liver disease were upregulated including: Insulin-like growth factorbinding protein 1, fatty acid-binding protein 3 and CYP7A1. The metabolic activity of hepatocytes cultured in fatty conditions was found to be impaired and the activities of CYP3A4 and CYP2C9 were significantlyreduced, similar to observations made in NAFLD patients. The utility of the model for drug screening was demonstrated by measuring the effects of known antisteatotic compounds. Hepatocytes, cultured under fatty conditions and treated with metformin, had a reduced cellular fat content compared to untreated controls and consumed less FFA from cell culture medium.CONCLUSION The 3D in vitro NAFLD model recapitulates many features of clinical NAFLD and is an ideal tool for analysing the efficacy of anti-steatotic compounds. | Tomasz Kostrzewski Terri Cornforth Sophie A Snow Larissa Ouro-Gnao Cliff Rowe Emma M Large David J Hughes | 2017 | World Journal of Gastroenterology2017,23,2: | 6 |
| 4 | Tenascin C upregulates interleukin-6 expression in human cardiac myofibroblasts via toll-like receptor 4显示文摘AIM:To investigate the effect of Tenascin C(TNC)on the expression of pro-inflammatory cytokines and matrixmetalloproteinases in human cardiac myofibroblasts(CMF).METHODS:CMF were isolated and cultured from patients undergoing coronary artery bypass grafting.Cultured cells were treated with either TNC(0.1μmol/L,24 h)or a recombinant protein corresponding to different domains of the TNC protein;fibrinogen-like globe(FBG)and fibronectin typeⅢ-like repeats(TNⅢ5-7)(both 1μmol/L,24 h).The expression of the proinflammatory cytokines;interleukin(IL)-6,IL-1β,TNFαand the matrix metalloproteinases;MMPs(MMP1,2,3,9,10,MT1-MMP)was assessed using real time RT-PCR and western blot analysis.RESULTS:TNC increased both IL-6 and MMP3(P<0.01)mR NA levels in cultured human CMF but had no significant effect on the other markers studied.The increase in IL-6 mR NA expression was mirrored by an increase in protein secretion as assessed by enzymelinked immunosorbant assay(P<0.01).Treating CMF with the recombinant protein FBG increased IL-6mR NA and protein(P<0.01)whereas the recombinant protein TNⅢ5-7 had no effect.Neither FBG nor TNⅢ5-7 had any significant effect on MMP3 expression.The expression of toll-like receptor 4(TLR4)in human CMF was confirmed by real time RT-PCR,western blot and immunohistochemistry.Pre-incubation of cells with TLR4neutralising antisera attenuated the effect of both TNC and FBG on IL-6 mR NA and protein expression.CONCLUSION:TNC up-regulates IL-6 expression in human CMF,an effect mediated through the FBG domain of TNC and via the TLR4 receptor. | Azhar Maqbool Emma J Spary Iain W Manfield Michaela Ruhmann Lorena Zuliani-Alvarez Filomena O Gamboa-Esteves Karen E Porter Mark J Drinkhill Kim S Midwood Neil A Turner | 2016 | World Journal of Cardiology2016,8,5: | 4 |
| 5 | Effectiveness of an intervention for reducing social stigma towards mental illness in adolescents显示文摘AIM: To evaluate the effectiveness of an intervention for reducing social stigma towards mental illness in adolescents. The effect of gender and knowledge of someone with mental illness was measured. METHODS: Two hundred and eighty secondary school students were evaluated using the Community Attitudes towards Mental Illness(CAMI) questionnaire. The schools were randomized and some received the intervention and others acted as the control group. The programme consisted of providing information via a documentary film and of contact with healthcare staff in order to reduce the social stigma within the school environment. RESULTS: The intervention was effective in reducing the CAMI authoritarianism and social restrictiveness subscales. The intervention showed significant changes in girls in terms of authoritarianism and social restrictiveness, while boys only showed significant changes in authoritarianism. Following the intervention, a significant reduction was found in authoritarianism and social restrictiveness in those who knew someone with mental illness, and only in authoritarianism in those who did not know anyone with mental illness. CONCLUSION: The intervention was effective to reduce social stigma towards people with mental illness, especially in the area of authoritarianism. Some differences were found depending on gender and whether or not the subjects knew someone with mental illness. | Regina Vila-Badia Francisco Martínez-Zambrano Otilia Arenas Emma Casas-Anguera Esther García-Morales Raúl Villellas José Ramón Martín María Belén Pérez-Franco Tamara Valduciel Diana Casellas Mar García-Franco Jose Miguel Joaquim Balsera Gemma Pascual Eugènia Julia Susana Ochoa | 2016 | World Journal of Psychiatry2016,6,2: | 4 |
| 6 | Nat Genet:单基因突变导致过敏性皮炎的发生显示文摘最近,研究者们鉴定出了一类导致神经性皮炎发生的关键基因突变:CARDll。来自美国NIH过敏与传染病研究所的研究者们通过对四个没有血缘关系的患病家庭进行分析,发现了这一导致疾病产生的基因、 | Chi A Ma, Yuan Zhang, Michael A Weinreich, Jonathan J Lyons, Celeste G Nelson, Thomas DiMaggio, Kelly D Stone, Joshua D Milner Jeffrey R Stinson, Elisa Ruffo, Batsukh Dorjbal, Swadhinya Arjunaraja, Kelsey Voss, Andrew L Snow Jordan K Abbott, Pia J Hauk, Paul R Reynolds, Erwin W Gelfand Elisa Ruffo Salomé Glauzy, Natsuko Yamakawa, Eric Meffre Jennifer Stoddard, Julie Niemela, Sergio D Rosenzweig Yu Zhang, Helen F Matthews Joshua J McElwee Nina Jones Alejandro Palma, Matías Oleastro, Emma Prieto, Andrea R Bernasconi, Geronimo Dubra, Silvia Danielian, Jonathan Zaiat, Marcelo A Marti Brian Kim Megan A Cooper Neil Romberg | 2017 | 现代生物医学进展2017,17,27: | 3 |
| 7 | Long-term outcomes of autoimmune pancreatitis: a multicentre, international analysis显示文摘 | Phil A Hart Terumi Kamisawa William R Brugge Jae Bock Chung Emma L Culver László Czakó Luca Frulloni Vay Liang W Go Thomas M Gress Myung-Hwan Kim Shigeyuki Kawa Kyu Taek Lee Markus M Lerch Wei-Chih Liao Matthias L?hr Kazuichi Okazaki Ji Kon Ryu Nicolas Sc | 2013 | Gut2013,,12: | 2 |
| 8 | Molecular nature of virulence in Entamoeba histolytica显示文摘 | Alfonso Olivos-García Emma Saavedra Espiridión Ramos-Martínez Mario Nequiz Ruy Pérez-Tamayo | 2009 | Infection Genetics and Evolution2009,,6: | 2 |
| 9 | Age at diagnosis of type 2 diabetes and cardiovascular risk factor profile:A pooled analysis显示文摘BACKGROUND The diagnosis of type 2 diabetes(T2D)in younger adults,an increasingly common public health issue,is associated with a higher risk of cardiovascular complications and mortality,which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age.AIM To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with T2D.METHODS A pooled dataset was used,comprised of data from five previous studies of adults with T2D,including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 years.Anthropometric and blood biomarker measurements included body weight,body mass index(BMI),waist circumference,body fat percentage,glycaemic control(HbA1c),lipid profile and blood pressure.Univariable and multivariable linear regression models,adjusted for diabetes duration,sex,ethnicity and smoking status,were used to investigate the association between age at diagnosis and each cardiovascular risk factor.RESULTS A higher proportion of participants diagnosed with T2D under the age of 40 were female,current smokers and treated with glucose-lowering medications,compared to participants diagnosed later in life.Participants diagnosed with T2D under the age of 40 also had higher body weight,BMI,waist circumference and body fat percentage,in addition to a more adverse lipid profile,compared to participants diagnosed at an older age.Modelling results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight[95%confidence interval(CI):0.52-0.82 kg],0.18 kg/m^(2) higher BMI(95%CI:0.10-0.25)and 0.32 cm higher waist circumference(95%CI:0.14-0.49),after adjustment for duration of diabetes and other confounders.Younger age at diagnosis was also significantly associated with higher HbA1c,total cholesterol,low-density lipoprotein cholesterol and triglycerides.CONCLUSION The diagnosis of T2D earlier in life is associated with a worse cardiovascular risk factor profile,compared to those diagnosed later in life. | Mary M Barker Francesco Zaccardi Emer M Brady Gaurav S Gulsin Andrew P Hall Joseph Henson Zin ZinHtike Kamlesh Khunti Gerald P McCann Emma L Redman David R Webb Emma G Wilmot Tom Yates Jian Yeo Melanie J Davies Jack A Sargeant | 2022 | World Journal of Diabetes2022,13,3: | 2 |
| 10 | The effects of acquired paternal obesity on the next generation显示文摘 | Neil A Youngson Emma Whitelaw | 2011 | Asian Journal of Andrology2011,13,2: | 2 |
| 11 | Evolving role of magnetic resonance techniques in primary sclerosing cholangitis显示文摘Development of non-invasive methods to risk-stratify patients and predict clinical endpoints have been identified as one of the key research priorities in primary sclerosing cholangitis(PSC). In addition to serum and histological biomarkers, there has been much recent interest in developing imaging biomarkers that can predict disease course and clinical outcomes in PSC.Magnetic resonance imaging/magnetic resonance cholangiopancreatography(MRI/MRCP) continue to play a central role in the diagnosis and follow-up of PSC patients. Magnetic resonance(MR) techniques have undergone significant advancement over the last three decades both in MR data acquisition and interpretation. The progression from a qualitative to quantitative approach in MR acquisition techniques and data interpretation, offers the opportunity for the development of objective and reproducible imaging biomarkers that can potentially be incorporated as an additional endpoint in clinical trials. This review article will discuss how the role of MR techniques have evolved over the last three decades from emerging as an alternative diagnostic tool to endoscopic retrograde cholangiopancreatography, to being instrumental in the ongoing search for imaging biomarker of disease stage, progression and prognosis in PSC. | Emmanuel A Selvaraj Emma L Culver Helen Bungay Adam Bailey Roger W Chapman Michael Pavlides | 2019 | World Journal of Gastroenterology2019,25,6: | 2 |
| 12 | An in vivo Comparison of Intestinal pH and Bacteria as Physiological Trigger Mechanisms for Colonic Targeting in Man显示文摘 | Emma L McConnell a Michael D Short Abdul W Basit | 2008 | Journal of Controlled Release2008,130,: | 1 |
| 13 | COCA: A Novel 3-D FE Simulator for the Design of TWTs Multistage Collectors显示文摘 | Coco S Emma F Laudani A | 2001 | IEEE Trans Electron Devices2001,48,1: | 1 |
| 14 | 'Novel' bromi natesd flame retardants in Belgian and UK indoor dust:implica- tions {or human exposure 显示文摘 | NADEEM A STUART H EMMA G | 2011 | Chemosphere2011,83,10: | 1 |
| 15 | The negativeeffects of bile acids and tumor necrosis factor-αon the tran-scription of cholesterol 7α-hydroxylase gene(CYP7A1)con-verge to hepatic nuclear factor-4显示文摘 | Emma De F Nico M Ana Cecilia A | 2001 | J Biol Chem2001,276,30: | 1 |
| 16 | Immunotherapy of insulin-dependent diabetes mellitus显示文摘 | EMMA L M JEFFREY A B | 2002 | Curr Opin Immunol2002,14,: | 1 |
| 17 | Seasonal variations in the disinfectionby-product precursor profile of reservoir water显示文摘 | Emma H Goslan D A Fearing J B | 2002 | AQUA2002,51,8: | 1 |
| 18 | Immunotherapy of insulin-dependent diabetes mellitus显示文摘 | Emma L M Jeffrey A B | 2002 | Current Opinion in Immunology2002,14,: | 1 |
| 19 | Rapid Blood-Pressure Low- ering in Patients with Acute Intracerebral Hemorrhage显示文摘 | Craig S A Emma H Yining H | 2013 | The New England Journal of Medicine2013,368,25: | 1 |
| 20 | Progressive rise in red cell distribution width is associated with poor outcome after transcatheter aortic valve implantation显示文摘 | Nay Aung Rafal Dworakowski Jonathan Byrne Emma Alcock Ranjit Deshpande Kailasam Rajagopal Beth Brickham Mark J Monaghan Darlington O Okonko Olaf Wendler Philip A MacCarthy Guleed Adan Samer H Ghozlan | 2013 | Heart2013,,: | 1 |