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Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason Philip Appleton Lisa J Woodhouse Craig s Anderson sandeep Ankolekar Lesley Cala Mark Dixon Timothy J England Kailash Krishnan Grant Mair Keith W Muir John Potter Christopher I Price Marc Randall Thompson G Robinson Christine Roffe Else C sandset Jeffrey L saver Angela shone Aloysius Niroshan siriwardena Joanna M Wardlaw Nikola sprigg Philip M Bath stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and Medical sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance service NHs Trust NottinghamUK stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK centre for Clinical Brain sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular sciences and NIHR Leicester Biomedical Research centre University of LeicesterLeicesterUK stroke Research in stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway Research and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and Comprehensive stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is ***,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scale(mRs)at day *** outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRs,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’*** were reported as n(%),mean(sD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%*** 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRs>2107(18%),Glasgow Coma scale 14(2)and time from onset to randomisation 67[45,108]***‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital *** Is ALREADY KNOWN ON THIs TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

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Inhibition of IL-11 signalling extends mammalian healthspan and lifespan

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四川生理科学杂志 2024年第7期46卷 1635-1635页

作者： Anissa A Widjaja Cardiovascular and Metabolic Disorders Program Duke–National University of Singapore Medical School Singapore Singapore National heart Research Institute singapore National Heart Centre Singapore Singapore Singapore Institute for Big Data and Artificial Intelligence in Medicine School of Science China Pharmaceutical University Nanjing China MRC Laboratory of Medical sciences London UK Barts heart centre Barts Health NHS Trust London UK Cardiovascular and Metabolic sciences Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) Berlin Germany DZHK (German centre for Cardiovascular Research) Partner Site Berlin Berlin Germany Charité–Universitätsmedizin Berlin Germany Institute of Clinical sciences Faculty of Medicine Imperial College London UK Bone Biology and Disease Unit St Vincent’s Institute of Medical Research Melbourne Victoria Australia Department of Medicine St Vincent’s Hospital The University of Melbourne Melbourne Victoria Australia

For healthspan and lifespan,ERK,AMPK and mTORC1 represent critical pathways and inflammation is a centrally important *** we examined whether IL-11,a pro-inflammatory cytokine of the IL-6 family,has a negative effect on age-associated disease and *** mice age,IL-11 is upregulated across cell types and tissues to regulate an ERK-AMPK-mTORC1 axis to modulate cellular,tissue-and organismal-level ageing *** of Il11 or Il11ra1 protects against metabolic decline,multi-morbidity and frailty in old age.

关键词： inflammation mTORC1 life

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When and how does brain-derived neurotrophic factor activate Nrf2 in astrocytes and neurons？

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Neural Regeneration Research 2018年第5期13卷 803-804页

作者： Tetsuro Ishii Giovanni E.Mann University of Tsukuba Tsukuba Japan school of Cardiovascular Medicine and sciences King's British Heart Foundation Centre of Excellence Faculty of Life Sciences and Medicine King's College Iondon London UK

Circadian rhythm protects neurons：Although the master clock entrains the whole body rhythm,peripheral tissues also express core clock transcription factors Clock and Bmal1,which regulate expression of clock genes including Period（Per）and Cryptochrome（Cry）*** of Per and Cry proteins repress Bmal1-and Clock-mediated transcription forming a negative feedback loop,which regulates nearly a 24 hours self-sustained rhythm including energy metabolism.

关键词： When and how does brain-derived neurotrophic factor activate Nrf2 in astrocytes and neurons NGF

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Renal denervation as an option for the management of hypertension

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The Journal of Biomedical Research 2014年第1期28卷 18-24页

作者： Georgina Radhini santiapillai Albert Ferro Department of Clinical Pharmacology Cardiovascular DivisionBritish Heart Foundation Centre of Research ExcellenceKing's College London

Hypertension is a multifactorial condition which makes the development of treatment approaches difficult. The vast majority of patients are treated with lifestyle measures either alone or in combination with antihypertensive drugs, and this approach is largely successful in controlling blood pressure. However, for a subgroup of patients, control of blood pressure remains resistant to this approach and therefore the development of new strategies is im- perative. The sympathetic nervous system has been known to be implicated in hypertension for many decades, and evidence from studies in the past has revealed the benefit of reducing sympathetic nerve activity in the control of blood pressure albeit with severe side effects. Recent technological advances have allowed for specific targeting of the renal sympathetic nerves by catheter ablation. The symplicity HTN-1 and HTN-2 trials have provided strong evidence for renal denervation giving rise to considerable blood pressure reductions in treatment-resistant hyper- tensives and, due to the high incidence of hypertension worldwide, this carries the promise of further reducing the global burden of hypertension and its attendant complications. Here we review the evidence for renal denervation in the management of hypertension.

关键词： hypertension renal denervation blood pressure

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Association of insomnia, insulin resistance traits and cardiovascular diseases risk: A two-step Mendelian randomization study

Association of insomnia, insulin resistance traits and cardi...

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中国睡眠研究会第十五届全国学术年会

作者： sizhi Ai Yanmin Xu Xiaoyu Wang shuo Ye Ruixiang Cui Yan Liang Hongliang Feng Yujing Zhou Xinyi Jin Xiao Tan Min Zhang Jihui Zhang The Affiliated Brain Hospital of Guangzhou Medical University The First Affiliated Hospital of Xinxiang Medical University Guangdong Provincial People's Hospital Zhejiang University school of Medicine king's college london british heart foundation centre of Research Excellence

Aims: Insomnia increases the risk of cardiovascular diseases(CVDs), but whether IR or its related traits mediate the underlying associations is *** conducted a two-step two-sample Mendelian randomization(MR) study to address these *** and results: We selected genetic variants of insomnia, IR and its traits(i.e., FG, FI, HbA1c, TG, HDL-C, and T2DM) as instrumental variables, while summary-level data of five CVDs(i.e., HF, CAD, AF, MI and hypertension) were served as the main outcomes, which derived from previous genome-wide association studies(GWAss).In the MR analysis, genetically predicted insomnia symptom was significantly associated with five CVDs risks and six IR related traits after correcting for multiple tests, while genetically predicted IR and related traits, such as T2DM, TG and HDL-C were associated with four CVDs *** the mediation analysis, we found strong evidence for the mediating effects of IR, TG, HDL-C, and T2DM in the causal pathway from insomnia to four CVDs except for ***, the major contributors were IR(ranging from 15.3% to 50.3% mediation) and T2DM(ranging from 8.4% to 28.9% mediation) among those potential *** MR analysis provided further evidence supporting the potential mediation effects of IR and related traits in the causal pathway between insomnia and ***: These results suggest that genetically predicted insomnia is associated with higher risk of CVDs, with considerable mediation by IR and *** on these factors may have the potential of substantially reducing the burden of CVDs attributable to insomnia.

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Delayed peripheral treatment with neurotrophin-3 improves sensorimotor recovery after central nervous system injury

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Neural Regeneration Research 2019年第10期14卷 1703-1704页

作者： sotiris G.Kakanos Lawrence D.F.Moon Neurorestoration Group Wolfson Centre for Age-Related DiseasesKing’s College of London

Neurotrophin-3 (NT3) is a growth factor found in many body tissues including the heart, intestines, skin, nervous system and in skeletal muscles including muscle spindles (Murase et al., 1994). NT3 is required for the survival, correct connectivity and function of sensory (“proprioceptive”) afferents that innervate muscle spindles;these neurons express receptors for NT3 including tropomyocin receptor kinase C. These proprioceptive afferents are important for normal movement (Boyce and Mendell, 2014) and signals from muscle spindles are important for recovery of limb movement (e.g., after spinal cord lateral hemisection)(Takeoka et al., 2014). The level of NT3 declines in most tissues during postnatal development;its level is low in adult and elderly humans and other mammals (Murase et al., 1994). Elevation of NT3 has been shown to improve outcome in various animal models of neurological disease and injury. For example, many groups have shown that delivery of NT3 directly into the central nervous system promotes recovery after spinal cord injury but this often involved invasive routes or gene therapy (Boyce and Mendell, 2014;Petrosyan et al., 2015;Wang et al., 2018).

关键词： Neurotrophin-3(NT3) tissues including the heart Boyce and Mendell

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Timing and mode of intervention for patients with left sided valvular heart disease:an individualized approach

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Precision Clinical Medicine 2018年第3期1卷 118-128页

作者： Hannah McConkey Zhengang Zhao s.Redwood M.Chen B.D.Prendergast king’s college london british heart foundation centre of Excellence The Rayne InstituteSt.Thomas’Hospital CampusLondonUnited Kingdomand the Department of CardiologyGuy’s and St.Thomas’NHS Foundation TrustLondonUnited Kingdom Department of Cardiology West China HospitalSichuan University

Left sided valvular heart disease poses major impact on life and *** therapy merely palliates chronic severe valve disease and once symptoms or haemodynamic sequelae appear,life expectancy is markedly *** this article,we review the mechanisms of valve pathology,latest evidence in the quest for pharmacological options,means by which to predict deterioration,and standard and novel treatment options.

关键词： markedly sided patients

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Inflammatory response to coronary artery bypass surgery: Does the heme-oxygenase-1 gene microsatellite polymorphism play a role?

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Chinese Medical Journal 2005年第15期118卷 1285-1290页

作者： LI Ping Jules sanders Emma Hawe David Brull Hugh Montgomery steve Humphries Cardiovascular Department Second Affiliated Hospital of Jiangxi Medical College Nanchang 330006 China centre for Cardiovascular Genetics British Heart Foundation Laboratories Department of Medicine Royal Free ＆ University College London Medical School Rayne Building 5 University Street London WC1E 6JF UK

Background Heme-oxygenase 1 （HO-1） is a rate-limiting enzyme in the degradation of heme to bilirubin, ferritin and carbon monoxide （CO） and may have significant anti-inflammatory function. The HO-1 gene promoter region shows microsatellite polymorphism with different （GT）n repeats, reported to differently induce gene expression, with the short allele associated with higher gene expression. We measured the acute inflammatory response using coronary artery bypass surgery （CABG） as a well-characterized and uniform stimulus and examined the correlation between levels of IL-6, C-reactive protein （CRP） and fibrinogen and their relationship to HO-1 genotype. Methods Two hundred and seventy-five consecutive patients undergoing CABG were genotyped for the HO-1 promoter polymorphism using PCR and automated DNA capillary sequencer. IL-6, CRP and fibrinogen were measured at baseline and 6, 24, 48, 72, 96 and 120 hours after CABG. Results Complete IL-6, CRP and fibrinogen measures were available in 220 patients. Before surgery IL-6 levels showed a strong correlation with CRP and fibrinogen （ r = 0. 48, P 〈 0. 0001 ; r = 0. 41, P 〈 0. 0001 respectively）, with a significant correlation between CRP and fibrinogen （r=0. 61, P 〈 0. 0001 ）. All three acute phase reactants showed a significant increase after CABG. After surgery, peak IL-6 was strongly correlated with peak CRP （r=0. 34, P =0.0009） but not with peak fibrinogen （r=0. 15, P =0. 13 ）, while peak CRP and peak fibrinogen were significantly correlated （r = 0. 15, P 〈 0. 0001 ）. HO-1 allelic repeats ranged from 22- 42, with （GT）25 and （GT）32 being the two most common alleles, and subsequently divided into three groups according to previous published work：〈 30 （GT） n were designated as s （short） , 30 - 37 （GT） n as M （middle） and long repeats with 〉 37 （GT） n as L （long） ; allele frequency 0. 35, 0. 58 and 0.07 respectively. Baseline CRP differed by genotype： those carrying at least one long allele having higher CRP than those

关键词： heine oxygenase polymorphism inflammation bypass surgery

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Reprogramming towards endothelial cells for vascular regeneration

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Genes & Diseases 2016年第3期3卷 186-197页

作者： Xuechong Hong Alexandra Le Bras Andriana Margariti Qingbo Xu Cardiovascular Division King’s College London BHF CentreLondonUK centre for Experimental Medicine School of MedicineDentistry and Biomedical SciencesQueen’s University BelfastBelfastUK

Endothelial damage and dysfunction are implicated in cardiovascular pathological changes and the development of vascular *** view of the fact that the spontaneous endothelial cell(EC)regeneration is a slow and insufficient process,it is of great significance to explore alternative cell sources capable of generating functional ECs to repair damaged ***,recent achievements of cell reprogramming to convert somatic cells to other cell types provide new powerful approaches to study endothelial *** on progress in the research field,the present review aims to summarize the strategies and mechanisms of generating endothelial cells through reprogramming from somatic cells,and to examine what this means for the potential application of cell therapy in the clinic.

关键词： Atherosclerosis Cell reprogramming Endothelial cells Endothelial regeneration iPs cells stem cells

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Endothelial Damage and stem Cell Repair in Atherosclerosis

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中国动脉硬化杂志 2009年第7期17卷 578-580页

作者： Qingbo Xu Cardiovascular Division King' s College London London UK

Atherosclerosis is an inflammatory disease characterized by leukocyte infiltration,smooth muscle cell accumulation and neointima formation[1]. Activation and damage of the endothelial monolayer seems to trigger the development of the lesions. Initially,it was thought that the damaged endothelial cells were replaced by the adjacent intact endothelium.

关键词：动脉粥样硬化细胞治疗方法临床分析

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