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麻醉与镇痛 2010年第2期6卷 75-82页

作者： Terence J. Gilhuly, MASc Bernard A. MacLeod, MD, FRCPC Guy A. Dumont, PhD Alex M. Bouzane, MSc, MD Stephan K. W. Schwarz 宋宗斌(译) 郭曲练(校) Department of Anesthesiology Pharmacology & Therapeutics Hugill Anesthesia Research Centre Department of Electrical and Computer Engineering Department of Anesthesia St. Paul's Hospital The University of British Columbia Vancouver B.C. Canada 不详

背景传统的单次推注肌肉松弛药的给药方式存在着手术中可控性有限、潜在的苏醒延迟和麻醉恢复期残余阻滞等问题。为此，我们开发了一种新的自适应电脑程序，即神经肌肉阻滞评价系^（NMBAS）。该程序以六阶拉盖尔模型及患者的肌电反应记... 详细信息

背景传统的单次推注肌肉松弛药的给药方式存在着手术中可控性有限、潜在的苏醒延迟和麻醉恢复期残余阻滞等问题。为此，我们开发了一种新的自适应电脑程序，即神经肌肉阻滞评价系^（NMBAS）。该程序以六阶拉盖尔模型及患者的肌电反应记录为基础，向麻醉医师提供肌肉松弛药的时效及剂量的建议。本研究中，我们对使用NMBAS后的神经肌肉阻滞是否优于常规治疗方法进行了探讨。方法这是一项随机、双盲、平行对照的前瞻性临床研究。73例接受腹部手术的患者（ASAI～Ⅲ级），使用罗库溴铵为肌肉松弛剂，全身麻醉时间≥1．5小时。患者分别按常规方式或NMBAS指导下给予罗库溴铵。主要结果变量为反映肌肉松弛不完善的围手术期事件发生率。次级变量包括手术后拮抗前4个成串刺激（TOF）比值，罗库溴铵总量，拮抗剂、麻醉药物及其他药物的用量，手术后不良事件的发生率以及麻醉医师不依从NMBAS建议的发生率。结果73例患者中，每组有30例符合统计分析的要求。两组问患者一般资料具有可比性。与常规组相比，NMBAS组患者围手术期肌肉松弛不完善相关事件的发生率明显降低（19／30VS8／30；P=0．004），NMBAS组平均TOF比值明显增高（0.59[95％CI：0．48～0．69]vs0．14[95％CI：0．04～0．24]；P〈0．0001）。罗库澳铵总量、拮抗剂、其他药物应用及手术后不良事件的发生率无差异。结论与常规方法相比，NMBAS指导的肌肉松弛方案可改善肌肉松弛质量，提高手术后TOF比值，减少肌肉松弛残余的危险性，提高患者围手术期的安全。

关键词：随机对照临床研究神经肌肉阻滞肌肉松弛药评价系统前瞻性临床研究罗库溴铵围手术期麻醉药物

Site-Specific Conjugation of Cell Wall Polyrhamnose to Protein SpyAD Envisioning a Safe Universal group A Streptococcal Vaccine

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Infectious Microbes & Diseases 2021年第2期3卷 87-100页

作者： Nina J.Gao Satoshi Uchiyama Lucy Pill Samira Dahesh Joshua Olson Leslie Bautista Shilpa Maroju Aym Berges Janet ZLiu Raymond HZurich Nina Mvan Sorge Jeff Fairman Neeraj Kapoor Victor Nizet Division of Host-Microbe Systems and therapeutics Department of PediatricsUC San DiegoLa JollaCaliforniaUSA Vaxcyte Inc.Foster CityCaliforniaUSA Department of Medical Microbiology and Infection Prevention Amsterdam University Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands Netherlands Reference Laboratory for Bacterial Meningitis Amsterdam University Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands Skaggs School of Pharmacy and Pharmaceutical Sciences UC San DiegoLa JollaCaliforniaUSA

Development of an effective vaccine against the leading human bacterial pathogen group A Streptococcus(GAS)is a public health *** species defining group A cell wall carbohydrate(GAC,Lancefield antigen)can be engineered to remove its immunodominant N-acetylglucosamine(GlcNAc)side chain,implicated in provoking autoimmune cross-reactivity in rheumatic heart disease,leaving its polyrhamnose core(GACPR).Here we generate a novel protein conjugate of the GACPR and test the utility of this conjugate antigen in active *** of conjugation to a standard carrier protein,we selected SpyAD,a highly conserved GAS surface protein containing both B-cell and T-cell epitopes relevant to the bacterium that itself shows promise as a vaccine *** was synthesized using the XpressTM cell-free protein expression system,incorporating a non-natural amino acid to which GACpr was conjugated by site-specific click chemistry to yield high molecular mass SpyAD-GACPR conjugates and avoid disruption of important T-cell and B-cell immunological *** conjugated SpyAD-GACPR elicited antibodies that bound the surface of multiple GAS strains of diverse M types and promoted opsonophagocytic killing by human *** immunization of mice with a multivalent vaccine consisting of SpyAD-GACPR,together with candidate vaccine antigens streptolysin O and C5a peptidase,protected against GAS challenge in a systemic infection model and localized skin infection model,without evidence of cross reactivity to human heart or brain tissue *** general approach may allow GAC to be safely and effectively included in future GAS subunit vaccine formulations with the goal of broad protection without autoreactivity.

关键词： group A Streptococcus Streptococcus pyogenes group A carbohydrate Lancefield antigen conjugate vaccine XpressCFTM non-natural amino acids SpyAD Introduction

Cutting edge advances in nanomedicine

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Science China(Life Sciences) 2012年第10期55卷 841-842页

作者： XIAO Han ZHANG YouYi Institute of Vascular Medicine of Peking University Third Hospital Ministry of Health Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides and Beijing Key Laboratory of Cardiovascular Receptors ResearchBeijing 100191China

Nanomedicine is the application of nanotechnology in medicine and is a revolutionary area in medical diagnostics and therapeutics using nanoscientific materials, tools, techniques and insight. Nanotechnology is the understanding and control of matter and processes at the nanoscale (1-100 nm) in one or more dimensions where size-dependent phenomena usually enable novel applications (http://***/).

关键词：纳米医学纳米技术癌症治疗应用程序纳米材料医疗诊断纳米尺度医学诊断

Generation and Characterization of a Nanobody Against SARS-CoV

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Virologica Sinica 2021年第6期36卷 1484-1491页

作者： Jiang-Fan Li Lei He Yong-Qiang Deng Shu-Hui Qi Yue-Hong Chen Xiao-Lu Zhang Shi-Xiong Hu Rui-Wen Fan Guang-Yu Zhao Cheng-Feng Qin State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyAcademy of Military Medical Sciences(AMMS)Beijing 100071China College of Veterinary Medicine Shanxi Agriculture UniversityJinzhong 030801China research Unit of Discovery and Tracing of Natural Focus Diseases Chinese Academy of Medical SciencesBeijing 100071China

The sudden emergence of severe acute respiratory syndrome coronavirus(SARS-CoV) has caused global panic in 2003,and the risk of SARS-CoV outbreak still exists. However, no specific antiviral drug or vaccine is available;thus, the development of therapeutic antibodies against SARS-CoV is needed. In this study, a nanobody phage-displayed library was constructed from peripheral blood mononuclear cells of alpacas immunized with the recombinant receptor-binding domain(RBD) of SARS-CoV. Four positive clones were selected after four rounds of bio-panning and subjected to recombinant expression in E. coli. Further biological identification demonstrated that one of the nanobodies, S14, showed high affinity to SARS-CoV RBD and potent neutralization activity at the picomole level against SARS-CoV pseudovirus. A competitive inhibition assay showed that S14 blocked the binding of SARS-CoV RBD to either soluble or cell-expressed angiotensinconverting enzyme 2(ACE2). In summary, we developed a novel nanobody targeting SARS-CoV RBD, which might be useful for the development of therapeutics against SARS.

关键词： Severe acute respiratory syndrome coronavirus(SARS-CoV) Receptor-binding domain(RBD) Nanobody Neutralizing antibody

A five-compartment model of age-specific transmissibility of SARS-CoV-2

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Infectious Diseases of Poverty 2020年第4期9卷 35-49页

作者： Ze-Yu Zhao Yuan-Zhao Zhu Jing-Wen Xu Shi-Xiong Hu Qing-Qing Hu Zhao Lei Jia Rui Xing-Chun Liu Yao Wang Meng Yang Li Luo Shan-Shan Yu Jia Li Ruo-Yun Liu Fang Xie Ying-Ying Su Yi-Chen Chiang Ben-Hua Zhao Jing-An Cui Ling Yin Yan-Hua Su Qing-Long Zhao Li-Dong Gao Tian-Mu Chen State Key Laboratory of Molecular Vaccinology and Molecular diagnostics School of Public HealthXiamen University4221-117 South Xiang'an RoadXiang'an DistrictXiamen City 361102Fujian ProvincePeople's Republic of China Hunan Provincial Center for Disease Control and Prevention 405 Furong Middle Road Section OneKaifu DistrictChangsha City 410001Hunan ProvincePeople's Republic of China Division of Public Health School of MedicineUniversity of Utah201 Presidents CircleSalt Lake CityUT 84112USA Department of Mathematics School of ScienceBeijing University of Civil Engineering and ArchitectureBeijingPeople's Republic of China Shenzhen Institutes of Advanced Technology Chinese Academy of SciencesShenzhenGuangdong ProvincePeople's Republic of China Jilin Provincial Center for Disease Control and Prevention 3145 Jingyang Big RoadLvyuan DistrictChangchun 130062Jilin ProvincePeople's Republic of China

Background:The novel coronavirus,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2,also called 2019-nCoV)causes different morbidity risks to individuals in different age *** study attempts to quantify the age-specific transmissibility using a mathematical ***:An epidemiological model with five compartments(susceptible-exposed-symptomatic-asymptomatic-recovered/removed[SEIAR])was developed based on observed transmission *** disease 2019(COVID-19)cases were divided into four age groups:group 1,those≤14years old;group 2,those 15 to 44years old;group 3,those 45 to 64years old;and group 4,those≥65 years *** model was initially based on cases(including imported cases and secondary cases)collected in Hunan Province from January 5 to February 19,*** dataset,from Jilin Province,was used to test the ***:The age-specific SEIAR model fitted the data well in each age group(Pgroup 4 to 3(median:β43=7.71×10-9;SAR43=3.86×10-8),followed by group 3 to 4(median:β34=3.07×10-9;SAR34=1.53×10-8),group 2 to 2(median:β22=1.24×10-9;SAR22=6.21×10-9),and group 3 to 1(median:β31=4.10×10-10;SAR31=2.08×10-9).The lowest transmissibility was from age group 3 to 3(median:β33=1.64×10-19;SAR33=8.19×10-19),followed by group 4 to 4(median:β44=3.66×10-17;SAR44=1.83×10-16),group 3 to 2(median:β32=1.21×10-16;SAR32=6.06×10-16),and group 1 to 4(median:β14=7.20×10-14;SAR14=3.60×10-13).In Jilin Province,the highest transmissibility occurred from age group 4 to 4(median:β43=4.27×10-8;SAR43=2.13×10-7),followed by group 3 to 4(median:β34=1.81×10-8;SAR34=9.03×10-8).Conclusions:SARS-CoV-2 exhibits high transmissibility between middle-aged(45 to 64 years old)and elderly(≥65 years old)***(≤14 years old)have very low susceptibility to *** study will improve our understanding of the transmission feature of SARS-CoV-2 in different age groups and suggest the most pre

关键词： Transmissibility SARS-CoV-2 COVID-19 Compartmental model Age-specific dynamics

Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease

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World Journal of Gastroenterology 2013年第30期19卷 4935-4943页

作者： Jan Sderman Elisabeth Norén Malin Christiansson Hanna Bragde Raphaele Thiébaut Jean-Pierre Hugot Curt Tysk Colm A O'Morain Miquel Gassull Yigael Finkel Jean-Frédéric Colombel Marc Lémann Sven Almer Division of Medical diagnostics Ryhov County Hospital55185 JnkpingSweden Department of Clinical and Experimental Medicine Linkping University58183 LinkpingSweden INSERM U843Université Paris DiderotHpital Robert Debré75019 ParisFrance Université ParisDiderot Sorbonne Paris-Cité UMR84375018 ParisFrance Assistance Publique-Hopitaux de Paris Hopital Robert Debré75019 ParisFrance Division of Gastroenterology Department of MedicineUniversity HospitalSchool of Health and Medical Sciencesrebro University70185 rebroSweden School of Health and Medical Sciences rebro University70185 rebroSweden Department of Gastroenterology Adelaide and Meath HospitalTallaghtDublin 24Ireland Trinity College Dublin College GreenDublin 2Ireland Health Sciences research Institute Germans Trias i Pujol08916 BadalonaSpain Department of Gastroenterology Sachs' Children's HospitalSdersjukhuset11861 StockholmSweden EPIMAD group Registre EPIMADService d'Epidémiologie et de Santé PubliqueHpital CalmetteCentre Hospitalier Universitaire de Lille59037 LilleFrance Icahn School of Medicine at Mount Sinai New YorkNY 10029United States GETAID group Groupe d'Etude Thérapeutiques des Affections Inflammatoires DigestivesService de gastroentérologieHpital Saint Louis75010 ParisFrance Department of Gastroenterology UHL County Council of stergtland58185 Link pingSweden Division of Gastroenterology Karolinska InstitutetDepartment of Gastroenterology and HepatologyKarolinska university hospital14186 StockholmSweden

AIM:To investigate a possible genetic influence of claudin(CLDN)1,CLDN2 and CLDN4 in the etiology of inflammatory bowel ***:Allelic association between genetic regions of CLDN1,CLDN2 or CLDN4 and patients with inflammatory bowel disease,Crohn's disease(CD)or ulcerative colitis were investigated using both a casecontrol study approach(one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls)and a family-based study(463 non-Swedish European inflammatory bowel disease-families).A nonsynonymous coding single nucleotide polymorphism in MORC4,located on the same linkage block as CLDN2,was investigated for association,as were two novel CLDN2 single nucleotide polymorphism markers,identified by ***:A single nucleotide polymorphism marker(rs12014762)located in the genetic region of CLDN2 was significantly associated to CD(case-control allelic OR = 1.98,95%CI:1.17-3.35,P = 0.007).MORC4 was present on the same linkage block as this CD *** the case-control approach,a significant association(case control allelic OR = 1.61,95%CI:1.08-2.41,P = 0.018)was found between CD and a nonsynonymous coding single nucleotide polymorphism(rs6622126)in *** association between the CLDN2 marker and CD was not replicated in the familybased *** colitis was not associated to any of the single nucleotide polymorphism ***:These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.

关键词： Crohn’s disease Genetic predisposition Inflammatory bowel disease Single nucleotide polymorphism Tight junctions

Highlights of the 2nd International Symposium on Tribbles and Diseases: tribbles tremble in therapeutics for immunity, metabolism, fundamental cell biology and cancer

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Acta Pharmaceutica Sinica B 2019年第2期9卷 443-454页

作者： Bing Cui Patrick A. Eyers Leonard L. Dobens Nguan Soon Tan Peter D. Mace Wolfgang A. Link Endre Kiss-Toth Karen Keeshan Takuro Nakamura Warren S. Pear Yodit Feseha Jessica Johnston Arkatiz Carracedo Marcel Scheideler Zabran llyas Robert C. Bauer Jorge D. Erusalimsky Dominika Grzesik Juan Salamanca-Viloria Xiaoxi Lv Yishi Jin Ke Li Guillermo Velasco Shuang Shang Jose M. Lizcano Xiaowei Zhang Jichao Zhou Jiaojiao Yu Fang Hua Feng Wang Shanshan Liu Jinmei Yu Zhuowei Hu State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Department of Biochemistry Institute of Integrative Biology University of Liverpool Division of Molecular Biology and Biochemistry School of Biological Sciences University of Missouri-Kansas City School of Biological Sciences Nanyang Technological University Lee Kong Chian School of Medicine Nanyang Technological University Institute of Molecular and Cell Biology KK Women's and Children Hospital Biochemistry Department School of Biomedical Sciences University of Otago Centre for Biomedical research (CBMR) University of Algarve Campus de Gambelas Department of Biomedical Sciences and Medicine University of Algarve Algarve Biomedical Center (ABC) University of Algarve Campus de Gambelas Department of Infection Immunity and Cardiovascular Disease University of Sheffield Paul O'Gorman Leukaemia research Centre Institute of Cancer Sciences University of Glasgow Division of Carcinogenesis The Cancer Institute Japanese Foundation for Cancer Research Department of Pathology and Laboratory Medicine Abramson Family Cancer Research Institute Perelman School of Medicine at the University of Pennsylvania Centre de Recherche en Transplantation et Immunologie (ou CRTI) Inserm Université de Nantes Nantes France Institut de Transplantation Urologie Néphrologie (ou ITUN) CIC bioGUNE CIBERONC Ikerbasque Basque Foundation for Science Biochemistry and Molecular Biology Department University of the Basque Country (UPV/EHU) Institute for Diabetes and Cancer IDC Helmholtz Center Munich Joint Heidelberg-IDC Translational Diabetes Program University Hospital Heidelberg Molecular Metabolic Control Medical Faculty Technical University Munich German Center for Diabetes research (DZD) Division of Cardiology Department of Medicine Columbia University Irving Medical Center School of Sport and Health Sciences Cardiff Metropolitan Universit

The Tribbles(TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of TRIB pseudokinases could provide new insights for disease development and help promote TRIB proteins as novel therapeutic targets for drug discovery. At the 2 nd International Symposium on Tribbles and Diseases held on May 7–9, 2018 in Beijing, China, a group of leading Tribbles scientists reported their findings and ongoing studies about the effects of the different TRIB proteins in the areas of immunity, metabolism, fundamental cell biology and cancer. Here, we summarize important and insightful overviews from 4 keynote lectures, 13 plenary lectures and 8 short talks that took place during this meeting. These findings may offer new insights for the understanding of the roles of TRIB pseudokinases in the development of various diseases.

关键词： Tribbles Immunology Metabolism Cell biology Kinase inhibitor Tumorigenesis Metastasis TRIB1 TRIB2 TRIB3 Pseudokinase Inflammation Atomic structure Protein quality control Ubiqutin

Design and synthesis of a novel siRNA with propargyl analogs at their 3'-overhang

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Design and synthesis of a novel siRNA with propargyl analogs...

Familial Alzheimer's disease modelling using induced pluripotent stem cell technology

第十一届全国化学生物学学术会议

作者： Chao Yang Dejun Ma Zhen Xi State Key Laboratory of Elemento-Organic Chemistry and National Engineering research Center of Pesticide College of ChernishyNankai Uniyersity

RNAi-based therapy has emerged as a powerful strategy for treatment of various diseases including cancer. The small interfering RNAs(siRNAs) could trigger-the target mRNA of disease-causing genes to be degraded in a highly sequence-specific manner. Although remarkable advances have been achieved,siRNA-based therapeutics is still limited mainly due to several challenges including low efficiency,fragile stability,poor specificity,imunostimulatory activity,and delivery barrier. The 2-nucleotide(nt) 3’-overhang of siRNAs is essential for their efficiency,and specificity,which contact directly with binding affinity between 3’-overhang and PAZ.4 Though different overhang structural have been explored,which include sugar limit,abasic,distance between phosphodiester backbone and nucleobase,enantioselectivity and steric hindrance, the design of more specific,potent and powerful siRNA molecules has been urgently *** by this context,we explored the effect of two isomerized nucleotide analog possessing propargyl group instead of nucleobase on potency and specificity of *** result showed that the silencing activities of siRNAs containing the β-analog(X) are almost equal to those of normal siRNAs with natural nucleosides at their 3’-overhang regions,and better than α-analog(Y) modified ***,lower binding of Y increased specificity of *** found that stronger binding happened between PAZ and β-analog not α-analog via atomistic simulations and free energy ***,the propargyl analog,described here do have function capable of triggering "click reaction" with *** work provides the guidance for the design of powerful and safe synthetic nucleotide analogues for substitution at the 3’-overhang.

关键词： RNAi-based therapy siRNAs propargyl analog 3’-overhang

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World Journal of Stem Cells 2014年第2期6卷 239-247页

作者： Lisa Mohamet Natalie J Miazga Christopher M Ward Stem Cell Biology group Core Technology FacilityFaculty of Human and Medical SciencesThe University of Manchester

Alzheimer’s disease(AD)is a progressive neurodegenerative disease in which patients exhibit gradual loss of memory that impairs their ability to learn or carry out daily *** of AD is difficult,particularly in early stages of the disease,and largely consists of cognitive assessments,with only one in four patients being correctly *** of novel therapeutics for the treatment of AD has proved to be a lengthy,costly and relatively unproductive process with attrition rates of>90%.As a result,there are no cures for AD and few treatment options available for ***,there is a pressing need for drug discovery platforms that can accurately and reproducibly mimic the AD phenotype and be amenable to high content screening ***,we discuss the use of induced pluripotent stem cells(iPSCs),which can be derived from adult cells,as a method of recapitulation of AD phenotype in *** assess their potential use in high content screening assays and the barriers that exist to realising their full potential in predictive efficacy,toxicology and disease *** present,a number of limitations need to be addressed before the use of iPSC technology can be fully realised in AD therapeutic ***,whilst the use of AD-derived iPSCs in drug discovery remains a fledgling field,it is one with immense potential that is likely to reach fruition within the next few years.

关键词： Human induced pluripotent stem cells Alzheimer’s disease Neurodegenerative diseases Highthroughput screening assays Cholinergic neurons Drug discovery Stratified medicine