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Relevance of placental type I interferon beta regulation for pregnancy success

Cellular & Molecular Immunology 2018年第12期15卷 1010-1026页

作者： Ja-Young Kwon Paulomi Aldo Yuan You Jiahui Ding Karen Racicot Xiaoyan Dong john Murphy guy glukshtad Michelle Silasi Jian Peng Li Wen Vikki MAbrahams Roberto Romero gil Mor Division of Reproductive Sciences Department of ObstetricsGynecology and Reproductive SciencesYale School of MedicineNew HavenCTUSA Department of Obstetrics and gynecology Institute of Women’s Life Medical ScienceYonsei University College of MedicineSeoulKorea Department of Obstetrics Gynecology&Reproductive BiologyCollege of Human MedicineMichigan State University400 Monroe Avenue NEGrand RapidsMI 49503USA Department of Pulmonary Shanghai Children’s HospitalShanghai Jiaotong University School of MedicineShanghaiChina Division of Endocrinology Department of Internal MedicineYale School of MedicineNew HavenCTUSA Perinatal Research Branch NICHD/NIHDetroitMIUSA

Pregnancy is a unique immunologic and microbial condition that requires an adequate level of awareness to provide a fast and protective response against pathogens as well as to maintain a state of tolerance to paternal *** of inflammatory pathways in the placenta triggered by pathogens is one of the main factors responsible for pregnancy *** I IFNs are key molecules modulating immune responses at the level of the placenta and are crucial for protection of the pregnancy via their antiviral and immune modulatory *** this study,we elucidate the mechanisms controlling the basal expression of IFNβand its negative *** in vitro and in vivo animal models,we found that TLR signaling maintains basal IFNβlevels through the TLR4-MyD88-independent TBK/IRF3 signaling *** describe the role of the TAM receptor Axl in the regulation of IFNβfunction in human and mouse trophoblast *** absence of TAM receptors in vivo is associated with fetal demise due to dysregulation of IFNβexpression and its pro-apoptotic downstream ***,our data describe a feedback signaling pathway controlling the expression and function of IFNβin the trophoblast that is essential for an effective response during viral and microbial infections.

关键词： trophoblast immune regulation cytokine TAM receptors type I interferon Interferon beta ISgs

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Targeting UDP-α-D-glucose 6-dehydrogenase alters the CNS tumor immune microenvironment and inhibits glioblastoma growth

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genes & Diseases 2022年第3期9卷 717-730页

作者： Daqian Zhan Fatih Yalcin Ding Ma Yi Fu Shuang Wei Bachchu Lal Yunqing Li Omar Dzaye john Laterra Mingyao Ying Hernando Lopez-Bertoni Shuli Xia Neurology Hugo IV.Moser Research Institute at Kennedy KriegerJohns Hopkins University School of MedicineBaltimoreMD 21205USA Department of Critical Care Medicine Tongji HospitalHuazhong University of Science and TechnologyWuhanHubei 430074PR China Department of Radiology and Neuroradiology ChariteBerlin 10117Germany Russell H.Morgan Department of Radiology and Radiological Science Johns Hopkins University School of MedicineBaltimoreMD 21205USA Department of Respiratory and Critical Care Medicine Tongji HospitalHuazhong University of Science and TechnologyWuhanHubei 430074PR China University Hospital Center Schleswig Holstein Department of NeurosurgeryKielSchleswig-Holstein 24105Germany Departments of Neurology Oncology and NeuroscienceJohns Hopkins University School of MedicineBaltimoreMD 21205USA Blood and Cell Therapy Institute University of Science and Technology of ChinaAnhui Provincial HospitalHefeiAnhui 230026PR China

glioblastoma(gBM,WHO grade IV glioma)is the most common and lethal malignant brain tumor in aduts with a dismal *** extracellular matrix(ECM)supports gBM progression by promoting tumor cell proliferation,migration,and immune *** diphosphate(UDP)-glucose 6-dehydrogenase(UgDH)is the rate-limiting enzyme that catalyzes the biosynthesis of glycosaminoglycans that are the principal component of the CNS *** investigated how targeting UgDH in gBM infuence$the gBM immune microenvironment,including tumor-associated microglia/macrophages(TAMs)and T *** are the main im-mune effector cells in gBM and can directly target tumor cells if properly *** co-cultures of gBM cells and human primary macrophages,UgDH knockdown in gBM cells pro-moted macrophage phagocytosis and M-like *** orthotropic human gBM xeno-grafts and syngeneic mouse glioma models,targeting UgDH decreased ECM deposition,increased TAM phagocytosis marker expression,reduced M2-like TAMS and inhibited tumor *** knockdown in gBM cells also promoted cytotoxic T cell ifltration and activa-tion in orthotopic syngeneic mouse glioma *** potent and in-human-use small mole-cule gAg synthesis inhibitor 4-methylumbelliferone(4-MU)was found to inhibit gBM cell proliferation and migration in vitro,mimic the macrophage and T-cell responses to UgDH knockdown in vitro and in vivo and inhibit growth of orthotopic murine *** study shows that UgDH supports gBM growth through multiple mechanisms and supports the development of ECM-based therapeutic strategies to simultaneously target tumor cells and their microenvi-ronment.

关键词： 4-MU Extracellular matrix(ECM) glioblastoma(gBM) Hyaluronic acid(HA) Phagocytosis T cells Tumor-associated microglia/macrophages(TAMs) UgDH

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Testicular fine-needle aspiration for the assessmen＇ of intratesticular hormone concentrations

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Asian Journal of Andrology 2016年第1期18卷 21-24页

作者： Ada P Lee Mara Y Roth Jean-Jacques Nya-Ngatchou Kat Lin Thomas J Walsh Stephanie T Page Alvin M Matsumoto William J Bremner john K Amory Bradley D Anawalt Department of Medicine University of California San Francisco San Francisco CA USA Department of Medicine and Center for Research in Reproduction and Contraception University of Washington Seattle WA USA Department of Obstetrics and gynecology University of Washington Seattle WA USA Department of Urology University of Washington Seattle WA USA Department of Medicine Geriatric Research Education and Clinical Center VA Puget Sound Health Care System Seattle WA USA.

Measurement of intratesticular sex steroid concentrations in men informs both the development of male hormonal contraceptives and the understanding of male infertility. given the challenges of using invasive techniques to measure testicular hormone physiology, our group has used a minimally-invasive fine-needle aspiration technique to measure intratesticular hormones in normal healthy men. Herein, we present a post-hoc analysis of the safety and efficacy of testicular fine-needle aspiration （FNA） completed as part of six clinical trials. From 2001 through 2011, a total of 404 procedures were conducted among 163 research volunteers, 85.9% of which were successful in obtaining sufficient fluid for the measurement of intratesticular steroid concentrations. Pain was the most common side effect, with 36.8% of procedures associated with moderate procedural pain and 4.7% with severe procedural pain. Postprocedural pain was uncommon and abated within a few days. Mild local bruising occurred with 14.9% of procedures. Two serious adverse events （0.5%） required surgical intervention. The risk of an adverse event was not associated with age, body mass index, testicular size, or the volume of fluid aspirated. Testicular FNA to obtain fluid for measurement of intratesticular steroid concentrations frequently causes mild to moderate procedural pain, but serious adverse events occur rarely. Testicular FNA has been instrumental for defining human intratesticular hormone physiology and is a minimally-invasive, safe, effective method for obtaining fluid for research on testicular physiology and pathology.

关键词： male contraception physiology reproductive and urinary testis

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人事任命与调动

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中国广告 2013年第2期 163-164页

作者： john Jay卸任W+K全球创意长

创意热店韦柯（Wieden＆kennedy）的创意宗9~johnJay日前已经卸任其担任已久的全球执行创意总监一职。并且启动与W＋K的合资公司W＋Kgarage。（garage：车库）

关键词：人事任命执行创意总监合资公司

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Low voltage wiring

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2002年

作者： ire alarm systems / Terrykennedy and john E. Traister.

ISBN: (纸本)9780071376747

Best-of-the-best guidelines for handling low voltage wiring The A-Z reference on designing, installing, maintaining, and troubleshooting modern security and fire alarm systems is now fully up-to-date in a new edition. Prepared by Terry kennedy and john E. Traister, authors with over three decades of hands-on experience apiece in the construction industry, Low Voltage Wiring: Security/Fire Alarm S

关键词： Fire alarms.Security systems industryLow voltage systems.

来源：畅想之星图书光盘版（南... 评论

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南宁市疑似脑膜炎患儿抗生素使用情况调查分析

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中国热带医学 2004年第4期4卷 512-514页

作者：梁大斌董柏青林玫唐振柱李翠云谭冬梅刘先知廖和壮吴兴华方锦嵩权怡秦卫文 Paul E.Kilgore W.A.kennedy 徐志一 john D.Clemens 广西壮族自治区疾病预防控制中心广西南宁530021 广西壮族自治区妇幼保健院广西南宁530021 International Vaccine Institute(IVI) Republic of Korea UCLA Center for Vaccine Research

目的　了解南宁地区疑似脑膜炎患儿抗生素的使用情况 ,以求规范、合理使用抗生素。　方法　使用统一的调查表格收集符合筛选标准的疑似脑膜炎患儿的相关资料 ,并进行流行病学统计、分析。　结果　共评估了 12 72例脑膜炎疑似患儿 ,使用... 详细信息

目的　了解南宁地区疑似脑膜炎患儿抗生素的使用情况 ,以求规范、合理使用抗生素。　方法　使用统一的调查表格收集符合筛选标准的疑似脑膜炎患儿的相关资料 ,并进行流行病学统计、分析。　结果　共评估了 12 72例脑膜炎疑似患儿 ,使用的抗生素以青霉素类 ( 75 0 0 % )和头孢菌素类 ( 64 2 3 % )为主 ;排前五位的是 :青霉素( 3 9 15 % )、头孢噻肟 ( 3 6 16% )、氨苄西林 ( 10 3 8% )、头孢拉定 ( 7 70 % )和头孢唑啉 ( 7 2 3 % )。 5 0 %以上的病例在就诊期间使用了 2种或 2种以上的抗生素 ,3 4 98%的病人在就诊前已使用了抗生素 ,注射途径给药的抗生素占 71 18% ;就诊期间注射给药的抗生素占 98 2 7%。年长儿青霉素使用率 ( 4 4 88% )较年龄较小的婴幼儿 ( 3 6 95 % )高 ,而新生儿较1个月以上的幼儿的头孢塞肟、氨苄西林、阿莫西林 -舒巴坦和头孢曲松的使用率高。脑脊液生化、常规异常和 /或血白细胞升高组抗生素使用率 ( 92 5 2 5 )较正常组 ( 83 165 )高。　结论　本调查中疑似脑膜炎患儿的抗生素治疗往往以引起该病的主要病原菌为依据 ,以经验用药为主 ,建议对类似病人应尽可能做病原学检查以指导治疗 ;

关键词：南宁市脑膜炎小儿抗生素病原学检查合理用药

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Identification of global DNA Methylation Signatures in glioblastoma-Derived Cancer Stem Cells

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Journal of genetics and genomics 2015年第7期42卷 355-371页

作者： Eun-Joon Lee Prakash Rath Jimei Liu Dungsung Ryu Lirong Pei Satish K.Noonepalle Austin Y.Shull Qi Feng N.Scott Litofsky Douglas C.Miller Douglas C.Anthony Mark D.Kirk john Laterra Libin Deng Hong-Bo Xin Xinguo Wang Jeong-Hyeon Choi Huidong Shi gRU Cancer Center Georgia Regents University Department of Biology College of Art and SciencesUniversity of Missouri Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological HealthFood and Drug Administration Department of Biochemistry and Molecular Biology Georgia Regents University Division of Neurological Surgery University of Missouri School of Medicine Department of Pathology and Anatomical Sciences University of Missouri School of Medicine Department of Pathology and Laboratory Medicine Brown University and Lifespan Academic Medical Center Department of Neurology The Hugo W.Moser Research Institute at Kennedy Krieger Inc.and The Johns Hopkins University School of Medicine Institute of Translational Medicine Nanchang University David H.Murdock Research Institute Department of Biostatistics and Epidemiology Georgia Regents University

glioblastoma （gBM） is the most common and most aggressive primary brain tumor in adults. The existence of a small population of stem-like tumor cells that efficiently propagate tumors and resist cytotoxic therapy is one proposed mechanism leading to the resilient behavior of tumor cells and poor prognosis. In this study, we performed an in-depth analysis of the DNA methylation landscape in gBM- derived cancer stem ceils （gSCs）. Parallel comparisons of primary tumors and gSC lines derived from these tumors with normal controls （a neural stem cell （NSC） line and normal brain tissue） identified groups of hyper- and hypomethylated genes that display a trend of either increasing or decreasing methylation levels in the order of controls, primary gBMs, and their counterpart gSC lines, respectively. Interestingly, concurrent promoter hypermethylation and gene body hypomethylation were observed in a subset of genes including MgMT, AJAP1 and PTPRN2. These unique DNA methylation signatures were also found in primary gBM-derived xenograft tumors indicating that they are not tissue culture-related epigenetic changes. Integration of gSC-specific epigenetic signatures with gene expression analysis further identified candidate tumor suppressor genes that are frequently down-regulated in gBMs such as SPINT2, NEFM and PENK. Forced re-expression of SPINT2 reduced glioma cell proliferative capacity, anchorage independent growth, cell motility, and tumor sphere formation in vitro. The results from this study demonstrate that gSCs possess unique epigenetic signatures that may play important roles in the pathogenesis of gBM.

关键词： glioblastoma Cancer stem cells DNA methylation SPINT2

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gALT基因Duarte变异体(N314D)对体外受精结果无效

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世界核心医学期刊文摘（妇产科学分册） 2006年第6期2卷 26-26页

作者： Yoshida S. Steele J. Koninckx J. S.kennedy 马超 Nuffield Department of Obstetrics and gynaecology University of Oxford John Radcliffe Hospital Oxford OX3 9DU United Kingdom

We assessed the effect of the Duarte (N314D) variant in the gALT gene on in vitro fertilization outcome measures. Our data do not definitely exclude variants in the gALT gene as factors influencing outcome, but the la... 详细信息

关键词：基因变异体 gALT 体外受精结果无效研究资料

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卫生系统知证政策指导：指导制定的基本原理和挑战

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中国循证医学杂志 2014年第7期14卷 777-782页

作者： Xavier Bosch-Capblanch john N. Lavis Simon Lewin Rifat Atun john-Arne Rottingen Daniel Droesche Lise Beck Edgardo Abalos Fadi El-Jardali Lucy gilson Sandy Oliver Kaspar Wyss Peter Tugwell Regina Kulier Tikki Pang Andy Haines 王琪(译) 吴琼芳(译) 陈耀龙(审校) 杨克虎(审校) Swiss Tropical and Public Health Institute BaselSwitzerland University of Basel BaselSwitzerland McMaster Health Forum Centre for Health Economics and Policy AnalysisDepartment of Clinical Epidemiology and Biostatisticsand Department of Political ScienceMcMaster UniversityHamiltonOntarioCanada Norwegian Knowledge Centre for the Health Services OsloNorwayand Health Systems Research UnitMedical Research Council of South AfricaCape TownSouth Africa global Fund to Fight AIDS Tuberculosis and MalariaGenevaSwitzerland Harvard kennedy School CambridgeMassachusettsUnited States of America Centro Rosarino de Estudios Perinatales RosarioArgentina Department of Health Policy and Management American University of BeirutBeirutLebanonand McMaster Health ForumMcMaster UniversityHamiltonOntarioCanada School of Public Health University of Cape Town and Department of Global Health and DevelopmentLondon School of Hygiene and Tropical MedicineUnited Kingdom EPPI-Centre Social Science Research UnitInstitute of EducationLondonUnited Kingdom Centre for global Health Institute of Population HealthUniversity of OttawaOttawaOntarioCanada Innovation InformationEvidence and ResearchWorld Health OrganizationGenevaSwitzerland Departments of Social and Environmental Health Research and of Nutrition and Public Health Research London School of Hygiene&Tropical MedicineLondonUnited Kingdom 兰州大学循证医学中心/中国gRADE中心兰州大学基础医学院兰州730000 甘肃省循证医学与临床转化重点实验室兰州730000

本文是《PLoS Medicine》关于卫生系统知证政策指导三篇系列文章的第一篇,阐述了应如何将证据转化为指导,以形成卫生系统政策,并促进临床和公共卫生干预的实施。其要点如下:①薄弱的卫生系统阻碍了有效干预的实施,加强此系统的政策需要... 详细信息

本文是《PLoS Medicine》关于卫生系统知证政策指导三篇系列文章的第一篇,阐述了应如何将证据转化为指导,以形成卫生系统政策,并促进临床和公共卫生干预的实施。其要点如下:①薄弱的卫生系统阻碍了有效干预的实施,加强此系统的政策需要基于当前可得的最佳证据;②卫生系统证据最好以政策制定过程参考的指导的形式呈现,但目前卫生系统指导制定质量较差;③将问题、干预及实施相关的研究转化为影响卫生系统组织方式的决策和政策是卫生系统指导制定面临的一个挑战;④制定及时且适用于广大卫生系统利益相关者的指导,并确定评价卫生系统指导质量的方法是另一个挑战;⑤改编现有方法(如用于临床指南的那些方法)制定有意义的建议来应对卫生系统、政策系统及背景的复杂性,尚需进一步研究。

关键词：卫生系统政策指导卫生干预最佳证据临床指南利益相关者 PLoS 制定过程

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Sox2 induces glioblastoma cell sternness and tumor propagation by repressing TET2 and deregulating 5hmC and 5mC DNA modifications

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Signal Transduction and Targeted Therapy 2022年第3期7卷 790-801页

作者： Hernando Lopez-Bertoni Amanda johnson Yuan Rui Bachchu Lai Sophie Sail Maureen Malloy Jonathan BCoulter Maria Lugo-Fagundo Sweta Shudir Harmon Khela Christopher Caputo Jordan J.green john Laterra Hugo W.Moser Research Institute at kennedy Krieger BaltimoreMDUSA Department of Neurology Johns Hopkins University School of MedicineBaltimoreMDUSA Department of Biomedical Engineering Institute for NanoBioTechnologyand the Translational Tissue Engineering CenterJohns Hopkins University School of MedicineBaltimoreMDUSA Bloomberg School of Public Health Department of Environmental Health and EngineeringThe Johns Hopkins University School of MedicineBaltimoreMDUSA The Department of Radiation Oncology and Molecular Radiation Sciences The Johns Hopkins University School of MedicineBaltimoreMDUSA Department of Ophthalmology Johns Hopkins University School of MedicineBaltimoreMDUSA Department of Oncology Johns Hopkins University School of MedicineBaltimoreMDUSA Departments of Materials Science&Engineering and Chemical&Biomolecular Engineering Johns Hopkins UniversityBaltimoreMDUSA Department of Neurosurgery Johns Hopkins University School of MedicineBaltimoreMDUSA Department of Neuroscience Johns Hopkins University School of MedicineBaltimoreMDUSA

DNA methylation is a reversible process catalyzed by the ten-eleven translocation(TET)family of enzymes(TET1,TET2,TET3)that convert 5-methylcytosine(5mC)to 5-hydroxymethylcytosine(5hmC).Altered patterns of 5hmC and 5m... 详细信息

关键词： TET2 5hmC convert

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