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The Triple Combination of Meropenem,Avibactam,and a Metallo-β-Lactamase Inhibitor Optimizes Antibacterial Coverage Against Different β-Lactamase Producers

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Engineering 2024年第7期38卷 124-132页

作者： Zhuoren Ling alistair james Macdonald Farley Aditya Lankapalli Yanfang Zhang Shonnette Premchand-Branker Kate Cook Andrei Baran Charlotte Gray-Hammerton Claudia Orbegozo Rubio Edgars Suna jordan Mathias jürgen Brem Kirsty Sands Maria Nieto-Rosado Maria Mykolaivna Trush Nadira Naznin Rakhi Willames Martins Yuqing Zhou Christopher joseph Schofield Timothy Walsh Department of Biology&Ineos Oxford Institute for Antimicrobial Research University of OxfordOxford OX13REUK Chemistry Research Laboratory Department of Chemistry and the Ineos Oxford Institute for Antimicrobial ResearchUniversity of OxfordOxford OX13TAUK Latvian Institute of Organic Synthesis Riga LV-1006Latvia Department of Medical Microbiology Division of Infection and ImmunitySchool of MedicineCardiff UniversityCardiff CF144XNUK Enzymology and Applied Biocatalysis Research Center Faculty of Chemistry and Chemical EngineeringBabes-Bolyai UniversityCluj-Napoca 400028Romania

This work explores the potential of a triple combination of meropenem(MEM),a novel metallo-blactamase(MBL)inhibitor(indole-2-carboxylate 58(InC58)),and a serine-b-lactamase(SBL)inhibitor(avibactam(AVI))for broad-spectrum activity against carbapenemase-producing bacteria.A diverse panel comprising MBL-and SBL-producing strains was used for susceptibility testing of the triple combination using the agar dilution *** frequency of resistance(FoR)to MEM combined with InC58 was *** were sequenced and tested for cross resistance,fitness,and the stability of the resistance *** with the double combinations of MEM plus an SBL or MBL inhibitor,the triple combination extended the spectrum of activity to most of the isolates bearing SBLs(oxacillinase-48(OXA-48)and Klebsiella pneumoniae carbapenemase-2(KPC-2))and MBLs(New Delhi metallo-blactamases(NDMs)),although it was not effective against Verona integron-encoded metallo-blactamase(VIM)-carrying Pseudomonas aeruginosa(***)and OXA-23-carrying Acinetobacter baumannii(***).The FoR to MEM plus InC58 ranged from 2.22×10^(-7)to 1.13×10^(-6).The resistance correlated with mutations to ompC and comR,affecting porin C and copper permeability,*** mutants manifested a fitness cost,a decreased level of resistance during passage without antibiotic pressure,and cross resistance to another carbapenem(imipenem)and a b-lactamase inhibitor(taniborbactam).In conclusion,compared with the dual combinations,the triple combination of MEM with InC58 and AVI showed a much wider spectrum of activity against different carbapenemaseproducing bacteria,revealing a new strategy to combat b-lactamase-mediated antimicrobial resistance.

关键词： Carbapenemase Metallo/serine-b-lactamase inhibitor Avibactam Meropenem Antimicrobial resistance

High-quality reconstruction of China’s natural streamflow

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Science Bulletin 2022年第5期67卷 547-556,M0004页

作者： Chiyuan Miao jiaojiao Gou Bojie Fu Qiuhong Tang Qingyun Duan Zhongsheng Chen Huimin Lei jie Chen jiali Guo alistair G.L.Borthwick Wenfeng Ding Xingwu Duan Yungang Li Dongxian Kong Xiaoying Guo jingwen Wu State Key Laboratory of Earth Surface Processes and Resource Ecology Faculty of Geographical ScienceBeijing Normal UniversityBeijing 100875China State Key Laboratory of Urban and Regional Ecology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China Key Laboratory of Water Cycle and Related Land Surface Processes Institute of Geographic Sciences and Natural Resources ResearchChinese Academy of SciencesBeijing 100101China College of Land and Resources China West Normal UniversityNanchong 637009China State Key Laboratory of Hydroscience and Engineering Department of Hydraulic EngineeringTsinghua UniversityBeijing 100084China State Key Laboratory of Water Resources and Hydropower Engineering Science Wuhan UniversityWuhan 430072China College of Hydraulic and Environmental Engineering China Three Gorges UniversityYichang 443002China Engineering Research Center of Eco-environment in Three Gorges Reservoir Region Ministry of EducationChina Three Gorges UniversityYichang 443002China School of Engineering the University of Edinburghthe King’s BuildingsEdinburgh EH93JLUK Changjiang River Scientific Research Institute Wuhan 430010China Institute of International Rivers and Eco-security Yunnan UniversityKunming 650091China

Reconstruction of natural streamflow is fundamental to the sustainable management of water *** China,previous reconstructions from sparse and poor-quality gauge measurements have led to large biases in simulation of the interannual and seasonal variability of natural *** we use a well-trained and tested land surface model coupled to a routing model with flow direction correction to reconstruct the first high-quality gauge-based natural streamflow dataset for China,covering all its330 catchments during the period from 1961 to 2018.A stronger positive linear relationship holds between upstream routing cells and drainage areas,after flow direction correction to 330 *** also introduce a parameter-uncertainty analysis framework including sensitivity analysis,optimization,and regionalization,which further minimizes biases between modeled and inferred natural streamflow from natural or near-natural *** resulting behavior of the natural hydrological system is represented properly by the model which achieves high skill metric values of the monthly streamflow,with about 83%of the 330 catchments having Nash-Sutcliffe efficiency coefficient(NSE)>0.7,and about56%of the 330 catchments having Kling-Gupta efficiency coefficient(KGE)>*** proposed construction scheme has important implications for similar simulation studies in other regions,and the developed low bias long-term national datasets by statistical postprocessing should be useful in supporting river management activities in China.

关键词： Natural streamflow Reconstruction Land surface model Parameter uncertainty analysis

选择性头部降温对胎羊缺血性脑损伤纹状体神经元的保护作用

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选择性头部降温对胎羊缺血性脑损伤纹状体神经元的保护作用

肿瘤特异性单克隆抗体与酵母β-葡聚糖联合用于抗瘤免疫治疗的研究进展

中华医学会第十四次全国儿科学术会议

作者：曹云邵肖梅 gunn Aj Bennet L George S Gluckman PD Gean j 骆菲复旦大学儿科医院新西兰奥克兰大学医学院Liggins研究所复旦大学妇产科医院

目的:研究选择性头部降温对缺血性脑损伤胎羊纹状体不同表型神经元的保护作用。方法:胎羊于妊娠117-124天(足月为147天)时通过双侧颈动脉阻塞30分钟造成双侧脑缺血损伤,损伤后胎羊随机分为:损伤组(n=10)、2小时治疗组(损伤后2小时开始...

目的:研究选择性头部降温对缺血性脑损伤胎羊纹状体不同表型神经元的保护作用。方法:胎羊于妊娠117-124天(足月为147天)时通过双侧颈动脉阻塞30分钟造成双侧脑缺血损伤,损伤后胎羊随机分为:损伤组(n=10)、2小时治疗组(损伤后2小时开始亚低温治疗,n=7)和6小时治疗组(损伤后6小时开始亚低温治疗,n=8),另设正常对照组(n=5)。通过冷循环水进行选择性头部降温,维持硬膜外温度为30-33℃,持续72小时。实验结束,取出胎羊,固定脑组织。用免疫组化法检测胎羊

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江苏大学学报（医学版） 2010年第4期20卷 365-368页

作者：刘晶晶 Lacey gunn Richard Hansen 严俊沈培美国路易斯维尔大学肿瘤研究中心肯塔基州路易斯维尔40202 江苏大学检验医学研究所免疫研究室

近年来提出了肿瘤特异性单克隆抗体(mAb)联合酵母β-葡聚糖用于肿瘤治疗的作用模式.已经证实,巨噬细胞能摄取、加工微粒子或大分子质量的可溶性β-葡聚糖,分泌活性物质,从而提高中性粒细胞补体受体3(complement receptor 3,CR3)水平,发... 详细信息

近年来提出了肿瘤特异性单克隆抗体(mAb)联合酵母β-葡聚糖用于肿瘤治疗的作用模式.已经证实,巨噬细胞能摄取、加工微粒子或大分子质量的可溶性β-葡聚糖,分泌活性物质,从而提高中性粒细胞补体受体3(complement receptor 3,CR3)水平,发挥对受iC3b调理的肿瘤细胞的杀伤作用.体内外试验证实,有效的抗瘤作用有赖于补体在肿瘤细胞上的沉积和激活,以及CR3在粒细胞上的表达.

关键词： β-葡聚糖肿瘤特异性单克隆抗体免疫治疗抗瘤作用酵母联合用 receptor

Regional Heterogeneity in 3D Myocardial Shortening in Hypertensive Left Ventricular Hypertrophy: A Cardiovascular CMR Tagging Substudy to the Life Study

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journal of Biomedical Science and Engineering 2015年第3期8卷 213-225页

作者： Robert W. W. Biederman alistair A. Young Mark Doyle Richard B. Devereux Eduardo Kortright Gilbert Perry jonathan N. Bella Suzanne Oparil David Calhoun Gerald M. Pohost Louis j. Dell’Italia Division of Cardiology Department of Cardiovascular CMR Gerald McGinnis Cardiovascular Institute Allegheny General Hospital Drexel University College of Medicine Pittsburgh USA University of Auckland Auckland New Zealand Weill Cornell Medical College New York USA ACTEK Inc. Birmingham USA University of Alabama at Birmingham Birmingham USA Albert Einstein College of Medicine Bronx USA University of Southern California Los Angeles USA

Background: Increased relative wall thickness in hypertensive left ventricular hypertrophy (LVH) has been shown by echocardiography to allow preserved shortening at the endocardium despite depressed LV midwall circumferential shortening (MWCS). Depressed MWCS is an adverse prognostic indicator, but whether this finding reflects reduced global or regional LV myocardial function, as assessed by three-dimensional (3D) myocardial strain, is unknown. Methods and Results: Cardiac Magnetic Resonance (CMR) tissue tagging permits direct evaluation of regional 3D intramyocardial strain, independent of LV geometry. We evaluated 21 hypertensive patients with electrocardiographic LVH in the LIFE study and 8 normal controls using 3D MR tagging and echocardiography. Patients had higher MR LV mass than normals (116 ± 40 versus 63 ± 6 g/m2, P = 0.002). Neither echocardiographic fractional shortening (32 ± 6 versus 33% ± 3%), LVEF (63% versus 64%) or mean end-systolic stress (175 ± 27 versus 146 ± 28 g/cm2) were significantly different, yet global MWCS was decreased by both echocardiography (13.4 ± 2.8 versus 18.2% ± 1.5%, P P P = 0.002) in LVH and greater in lateral and anterior regions versus septal and posterior regions ( P P P 0.60, P = 0.001 for both). Conclusions: In patients with hypertensive LVH, despite normal LV function via echocardiography or CMR, CMR intramyocardial tagging show depressed global MWCS while 3D MR strain revealed marked underlying regional heterogeneity of LV dysfunction.

关键词： Hypertension Left Ventricular Hypertrophy Magnetic Resonance Imaging Cardiac Mechanics Heart Wall Motion 3D

选择性头部降温对胎羊缺血性脑损伤纹状体神经元的保护作用

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选择性头部降温对胎羊缺血性脑损伤纹状体神经元的保护作用

选择性头部降温对胎羊缺血性脑损伤纹状体神经元的保护作用

第三届长三角围产医学学术论坛暨2006年浙江省围产医学学术年会

作者：曹云骆菲 gunn Aj Bennet L George S Gluckman PD 邵肖梅 Guan j 复旦大学儿科医院复旦大学妇产科医院新西兰奥克兰大学医学院Liggins研究所

目的研究选择性头部降温对缺血性脑损伤胎羊纹状体不同表型神经元的保护作用。方法胎羊于妊娠117-124天(足月为147天)时通过双侧颈动脉阻塞30分钟造成双侧脑缺血损伤,损伤后胎羊随机分为:损伤组(n=10)、2小时治疗组(损伤后2小时开始亚...

目的研究选择性头部降温对缺血性脑损伤胎羊纹状体不同表型神经元的保护作用。方法胎羊于妊娠117-124天(足月为147天)时通过双侧颈动脉阻塞30分钟造成双侧脑缺血损伤,损伤后胎羊随机分为:损伤组(n=10)、2小时治疗组(损伤后2小时开始亚低温治疗,n=7)和6小时治疗组(损伤后6小时开始亚低温治疗n=8),另设正常对照组(n=5)。通过冷循环水进行选择性头部降温,维持硬膜外温度为30-33℃,持续72小时。实验结束,取出胎羊,固定脑组织。用免

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选择性头部降温对胎羊缺血性脑损伤纹状体神经元的保护作用

诊断性试验和策略的证据质量和推荐强度的分级

2006（第三届）江浙沪儿科学术会议暨浙江省儿科学术年会

作者：骆菲曹云 gunn Aj Bennet L George S Gluckman PD 邵肖梅陈莲 Guan j 复旦大学妇产科医院新西兰奥克兰大学医学院Liggins研究所复旦大学儿科医院

目的研究选择性头部降温对缺血性脑损伤胎羊纹状体不同表型神经元的保护作用。方法胎羊于妊娠117～124天(足月为147天)时通过双侧颈动脉阻塞30分钟造成双侧脑缺血损伤,损伤后胎羊随机分为:损伤组(n=10)、2小时治疗组(损伤后2小时开始亚...

目的研究选择性头部降温对缺血性脑损伤胎羊纹状体不同表型神经元的保护作用。方法胎羊于妊娠117～124天(足月为147天)时通过双侧颈动脉阻塞30分钟造成双侧脑缺血损伤,损伤后胎羊随机分为:损伤组(n=10)、2小时治疗组(损伤后2小时开始亚低温治疗,n=7)和6小时治疗组(损伤后6小时开始亚低温治疗,n=8),另设正常对照组(n=5)。通过冷循环水进行选择性头部降温,维持硬膜外温度为30～33℃,持续72小时。实验结束,取出胎羊,固定脑组织。用免疫

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中国循证医学杂志 2009年第5期9卷 503-508页

作者： Holger j Schünemann Andrew D Oxman jan Brozek Paul Glasziou Roman jaeschke gunn E Vist john W Williams jr Regina Kunz jonathan Craig Victor M Montori Patrick Bossuyt Gordon H Guyatt 李晓黄程陈耀龙李幼平代表GRADE工作组

GRADE系统能对诊断性试验或策略的证据质量和推荐强度进行分级。本文旨在阐释在此过程中如何考虑患者的重要结局，

关键词：诊断性试验证据质量强度 E系统

42岁男性急性胸痛一例:病人的观点与医生的评论

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英国医学杂志中文版 2004年第3期7卷 185-187页

作者： Gottfried Sodeck Harald Herkner alistair Howitt Irene Lang Ed Peile 杨靓 registrar Department of Emergency Medicine vienna General HospitalAustria consultant Department of Emergency Medicine Vienna General HospitalAustria general practitioner.Warders Medical Centre East Street TonbridgeKent TN9 ILA Consultant Cardiologist University of Vienna Austria associate director of clinical studies Division of Public Health and primary Health Care University of Oxford.

评论:病人的观点Peter Hartl,病人本人,Gottfried Sodeck,住院医生当医生们第一次邀请我参加关于我自己的病例讨论时,我拒绝了。因为我不知道怎样贴切的表达我的感想。但是,我让我的妻子与Gottfried Sodeck医生进行沟通,在他们的劝说下... 详细信息

评论:病人的观点Peter Hartl,病人本人,Gottfried Sodeck,住院医生当医生们第一次邀请我参加关于我自己的病例讨论时,我拒绝了。因为我不知道怎样贴切的表达我的感想。但是,我让我的妻子与Gottfried Sodeck医生进行沟通,在他们的劝说下,我最终同意参与讨论我的病例。总之,参加互动式病例讨论对我来说是个有趣的经历。

关键词：男性急性胸痛病人观点医生评论