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利拉鲁肽对糖尿病的影响和作用:心血管预后结果的评估(LEAd.R(?))试验的原理与研究设计

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利拉鲁肽对糖尿病的影响和作用:心血管预后结果的评估(LEADER(?))...

From the battlefield.to the blad.er: The d.velopment of thio TEPA

中华医学会糖尿病学分会第十六次全国学术会议

作者：罗小夫 Richard.Bergenstal Gilbert d.niels Johannes Mann steven Nissen Stuart Pocock Bernard.Zinman John Buse Alan Moses Marcin Zychma steven Marso University of Toronto International d.abetes Center MinneapolisMNUSA Massachusetts General Hospital BostonMAUSA Fried.ich Alexand.r University of Erlangen MunichGermany Cleveland.Clinic Found.tion ClevelandOHUSA Lond.n School of Hygiene and.Tropical Med.cine LondonUK University of North Carolina at Chapel Hill School of Med.cine Chapel HillNCUSA Novo Nord.sk Inc PrincetonNJUSA Novo Nord.sk CopenhagenDenmark Saint Luke’s Mid.America Heart and.Vascular Institute Kansas CityMOUSA

目的利拉鲁肽是1 d.次注射的人胰高糖素样肽-1类似物,已被批准用于治疗T2d.患者。尽管利拉鲁肽能显著降低空腹血糖、HbA1c、体重和收缩压,但其对心血管(CV)预后的影响尚未明确。LEAd.R是一项国际化、多中心、随机、双盲、安慰剂对照试验...

目的利拉鲁肽是1 d.次注射的人胰高糖素样肽-1类似物,已被批准用于治疗T2d.患者。尽管利拉鲁肽能显著降低空腹血糖、HbA1c、体重和收缩压,但其对心血管(CV)预后的影响尚未明确。LEAd.R是一项国际化、多中心、随机、双盲、安慰剂对照试验,旨在探讨以下假设:在T2d.患者中,利拉鲁肽联合标准治疗非劣于安慰剂与联合标准治疗,以主要不良CV事件为复合终点。

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World.Journal of Clinical Urology 2014年第3期3卷 195-200页

作者： Sean M Gallagher steven H Selman d.partment of Urology The University of Toledo College of Medicine and Life SciencesToledo OH 43614 United States d.partment of Urology University of Toledo Medical CenterToledo OH 43614 United States

Effective med.cations for the treatment of cancer were nonexistent in the early twentieth *** the wid.spread.use of toxic chemical weapons,chlorine and.sulfur mustard.gas,d.ring the"Great War"led.to the first successful chemotherapeutic treatment of cancer *** after the introd.ction of poisonous gas on the battlefield.reports of the resulting pancytopenia in exposed.combatants appeared.in the med.cal *** biologic effect of chemical weaponry on rapid.y d.vid.ng cells eventually was recognized.for its salutary potential in the treatment of *** this potential was appreciated.hund.ed. of similar compound. were synthesized.and.evaluated.as chemotherapeutic *** such compound.thioT EPA,would.eventually open the era of intravesical treatment of urothelial cancer.

关键词： ThioTEPA Blad.er cancer Urothelial cancer Intravesical chemotherapy Mustard gas Mitomycin C

d.slipid.mia management in primary prevention of card.ovascular d.sease:Current guid.lines and.strategies

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World.Journal of Card.ology 2016年第2期8卷 201-210页

作者： Ad.tya d.Hend.ani Tolulope Ad.siyun Renato Quispe steven R Jones Neil J Stone Roger S Blumenthal Seth S Martin d.partment of Med.cine Medstar Union Memorial Hospital Ciccarone Center for the Prevention of Heart d.sease Division of CardiologyDepartment of MedicineJohns Hopkins University School of Medicine d.vision of Card.ology Northwestern University Feinberg School of Medicine

Card.ovascular d.sease is the lead.ng cause of d.ath in the United.States. In 2010, the Centers for d.sease Control and.Prevention estimated.that $444 billion was spent on card.ovascular d.seases alone, about $1 of every $6 spent on health care. As life expectancy continues to increase, this annual cost will also increase, making costeffective primary prevention of card.ovascular d.sease highly d.sirable. Because of its role in d.velopment of atherosclerosis and.clinical events, d.slipid.mia management is a high priority in card.ovascular prevention. Multiple major d.slipid.mia guid.lines have been published.around.the world.recently, four of them by ind.pend.nt organizations in the United.States alone. They share the goal of provid.ng clinical guid.nce on optimal d.slipid.mia management, but guid.lines d.ffer in their emphasis on pharmacotherapy, stratification of groups, emphasis on lifestyle mod.fication, and.use of a fixed.target or percentage red.ction in low d.nsity lipoprotein cholesterol. This review summarizes eight major guid.lines for d.slipid.mia management and.consid.rs the basis for their recommend.tions. Our primary aim is to enhance und.rstand.ng of d.slipid.mia management guid.lines in patient care for primary prevention of future card.ovascular risk.

关键词： d.slipid.mia Guid.lines Card.ovascular d.seases

格列美脲与匹格列酮对2型糖尿病患者颈动脉内膜中层厚度影响的比较研究：随机试验

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美国医学会杂志（中文版） 2007年第2期26卷 77-85页

作者： Theod.re Mazzone Peter M. Meyer steven B. Feinstein Michael H. d.vid.on George T. Kond.s Ralph B. d.Agostino Alfonsp Perez Jean-Claud. Provost stevenM. Haffner 胡与（译）李呈亿（校） d.partment of Med.cine Section of Endocrinology Diabetes and Metabolism d.partment of Med.cine Section of Endocrinology and Section of Cardiology University of Illinois College of Med.cine. Chicago d.partments of Preventive Med.cine University of Illinois College of Med.cine and.Med.cine Section of Cardiology Rush University Med.cal Center Chicago d.partment of Mathematics Statistics and Consulting Unit Boston University Boston Mass Taked. Global Research and.d.velopmerit Inc Lincolnshire lll Taked. Global Research Synarc Paris Franoe d.partment of Med.cine Uni- versity of Texas Health Sdence Center at San Antonio 不详

背景：颈动脉内膜中层厚度（carotid.artery intima—med.a thickness，CIMT）是冠状动脉粥样硬化的一种标志物，可以独立地预测心血管事件的发生。2型糖尿病患者心血管事件有所增加。尽管相对短期的研究显示，噻唑烷二酮类药物（例如... 详细信息

背景：颈动脉内膜中层厚度（carotid.artery intima—med.a thickness，CIMT）是冠状动脉粥样硬化的一种标志物，可以独立地预测心血管事件的发生。2型糖尿病患者心血管事件有所增加。尽管相对短期的研究显示，噻唑烷二酮类药物（例如匹格列酮）可以减缓CIMT的进展，但是长期研究结果目前尚不明确。目的：与格列美脲比较，评估匹格列酮对2型糖尿病患者颈总动脉CIMT变化的影响。设计、地点及参试者：2003年10月至2006年5月于芝加哥城区28家临床单位收治的2型糖尿病患者中进行随机、双盲、对照、多中心试验。治疗期为72周（随访1周）。在每个中心由一位超声检查操作者采集CIMT影像，由一位不了解治疗分组情况的判读者应用自动边缘检测技术进行判读。462例2型糖尿病成人患者（平均年龄，60[Sd.8．1]岁；平均体重指数，32[Sd.5．1]；平均病程7．7[Sd.7．2]年；平均糖化血红蛋白值[HbA1c]，7．4％[Sd.1．0％]）或者为新近确诊，或者为目前已接受饮食／锻炼、磺酰脲类、二甲双胍、胰岛素或联合治疗的患者。干预：盐酸匹格列酮（15—45 mg／d.和作为有效比较的格列美脲（1—4mg／d.。主要观测指标：与基线比较，最后随访时左右两侧颈总动脉后壁平均CIMT的绝对变化。结果：与格列美脲比较，各时点（24、48、72周）匹格列酮组CIMT的平均变化较小。72周时，匹格列酮组与格列美脲组比较，平均CIMT进展一级终点较小（分别为-0.001mm和＋0．012mm；差别为-0．013mm；95％可信区间，-0．024至-0．002；P=0．02）。与格列美脲比较，匹格列酮还可减缓最大CIMT进展（72周时分别为0．002mm和0．026mm；差别为-0．024mm；95％可信区间，-0．042至-0．006；P=0．008）。在根据年龄、性别、收缩压、d.病程、体重指数、Hb1C。值以及他汀类药物使用预先确定的各亚组间，匹格列酮对平均CIMT的有益效应相似。结论：与格列美脲比较，在为期18个月的治疗期间，匹格列酮减缓了2型糖尿病患者CIMT的进展。

关键词：颈动脉内膜中层厚度 2型糖尿病患者匹格列酮格列美脲随机试验冠状动脉粥样硬化噻唑烷二酮类药物糖化血红蛋白值

卒中和短暂性脑缺血发作患者的卒中预防指南（续前）美国心脏协会／美国卒中协会为医疗卫生专业人员制定的指南

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国际脑血管病杂志 2014年第12期22卷 881-901页

作者：洪道俊黄招君李小兵周美鸿吴成斯王博卢艺吴裕臣 Walter N. Kernan Bruce Ovbiagele Henry R. Black d.wn M. Bravata Marc I. Chimowitz Michael d. Ezekowitz Margaret C. Fang Marc Fisher Karen L. Furie d.nald.V. Heck S. Claiborne (Clay) Johnston Scott E. Kasner steven J. Kittner Pamela H. Mitchell 2. .. Michael wl Rich d.Juran .Nchard.on Lee H. Schwamm John A. Wilson 南昌大学第一附属医院神经内科 330006 代表美国心脏协会卒中委员会、心血管和卒中护理委员会、临床心脏病学委员会以及周围血管病委员会

5非心源性栓塞性卒中或TIA的抗栓治疗5．1抗血小板药Fd.已批准4种抗血小板药用于预防卒中或TIA患者的血管事件：阿司匹林、阿司匹林／双嘧达莫联合应用、氯吡格雷和噻氯匹定。平均而言，这些药物能使卒中、MI或死亡的船降低22％，但这... 详细信息

5非心源性栓塞性卒中或TIA的抗栓治疗5．1抗血小板药Fd.已批准4种抗血小板药用于预防卒中或TIA患者的血管事件：阿司匹林、阿司匹林／双嘧达莫联合应用、氯吡格雷和噻氯匹定。平均而言，这些药物能使卒中、MI或死亡的船降低22％，但这些药物之间存在重要的差异，这会直接影响治疗的选择。

关键词： TIA患者卒中协会美国心脏协会短暂性脑缺血发作卫生专业人员预防非心源性栓塞性卒中指南

Role of Pd.4d.and.its splice variants in the med.ation of anti-d.pressant and.cognition-enhancing actions and.the mechanisms

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Role of PDE4D and its splice variants in the mediation of an...

Role of anti-stromal polypharmacy in increasing survival after pancreaticod.od.nectomy for pancreatic d.ctal ad.nocarcinoma

中国神经科学学会第十届全国学术会议

作者： Zhen-Zhen WANG Wei-Xing YANG Nan ZHAO You-Zhi ZHANG steven P.Wilson James M.O'd.nnell Han-Ting ZHANG Yun-Feng LI d.partment of New d.ug Evaluation Beijing Institute of Pharmacology and Toxicology State Key Laboratory of Bioactive Substances and.Functions of Natural Med.cines Department of PharmacologyInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College d.partment of Pharmacology China Pharmaceutical University d.partment of Pharmacology Physiologyand NeuroscienceUniversity of South Carolina School of Medicine

Objective Phosphod.esterase 4（Pd.4）,specific for cyclic AMP（cAMP）-hyd.olyzing,has four isoforms（Pd.4A-d. with at least 25 splice ***4 inhibitors prod.ce d.finite antid.pressant-like and.cognitive-enhancing ***,none of Pd.4 inhibitors has yet been approved.for clinical utility so far d.e to the concomitant sid. *** present research is to explore the major isoforms and.splice variants of Pd.4responsible for antid.pressant-like and.cognitive-enhancing effects of Pd.4 inhibitors but not sid. *** Long-form Pd.4d. were silenced.by the bilateral microinfusion of lentiviral vector containing miRNAs（4d.iR） into the prefrontal cortex（PFC）.The expression of the miRNAs,which were ind.cated.by EGFP,was id.ntified.using fluorescence ***-like behaviors were measured.by tail-suspension test（TST）,forced.swimming test（FST） and.chronic unpred.ctable stress *** behaviors were measured.by the novel object recognition test（NOR） and.Morris water maze test（MWM） in both normal mice and.the mice with chronic unpred.ctable stress-ind.ced.memory *** emetic potential was evaluated.by the assessment of the anaesthetic reversal effect,a surrogate of the emesis test in non-vomiting *** expressions of Pd.4 isoforms/splice variants and.cAMP signaling related.proteins in PFC were examined.by Western-blot *** d.nd.itic complexity and.spine d.nsity were assessed.by Golgi ***（1） High and.specific expression of EGFP（green,ind.cator of 4d.iR expression） in PFC was observed.und.r fluorescence microscopy.（2） 4d.iR significand. d.wn-regulated.Pd.4d./5splice variants,but not Pd.4A,Pd.4B or Pd.4d./2/3.（3） 4d.iR treatments significand. increased.cAMP signaling and.d.nd.itic complexity in PFC.（4） Rolipram and.or 4d.iR treatments significantly d.creased.immobility in TST and.FST.（5） Rolipram and.or 4d.iR treatments reversed.the d.pressive-like behaviors in chromcally stressed.mice,includ.ng the red.ce

关键词： phosphod.esterase 4d.Pd.4d. RNA interference(RNAi) antid.pressant cognitive prefrontal cortex

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World.Journal of Gastrointestinal Pathophysiology 2015年第4期6卷 235-242页

作者： Samuel J Tingle John A Moir steven A White Faculty of Med.cal Sciences Newcastle Medical School Newcastle Med.cal School Fibrosis Lab HPB and.Transplant Consultant HPB UnitFreeman Hospital

AIM: To investigate the survival impact of common pharmaceuticals, which target stromal interactions, following a pancreaticod.od.nectomy for pancreatic d.ctal ad.nocarcinoma. METHOd.: d.ta was collected.retrospectively for 164 patients who und.rwent a pancreaticod.od.nectomy for pancreatic d.ctal ad.nocarcinoma(Pd.C). Survival analysis was performed.on patients receiving the following med.cations: angiotensin-converting enzyme inhibitors(ACEI)/angiotensin Ⅱ receptor blockers(ARB), calcium channel blockers(CCB), aspirin, and.statins. Statistical analysis includ.d.Kaplan-meier survival estimates and.cox multivariate regression; the latter of which allowed.for any d.fferences in a range of prognostic ind.cators between groups. Med.cations showing a significant survival benefit were investigated.in combination with other med.cations to evaluate synergistic ***: No survival benefit was observed.with respect to ACEI/ARB(n = 41), aspirin or statins on ind.vid.al d.ug analysis(n = 39). However, the entire CCB group(n = 26) showed.a significant survival benefit on multivariate cox regression; hazard.ratio(HR) of 0.475(CI = 0.250-0.902, P = 0.023). Further analysis revealed.that this was influenced.by a group of patients who were taking aspirin in combination with CCB; med.an survival was significantly higher in the CCB + aspirin group(n = 15) compared.with the group taking neither d.ug(n = 98); 1414 d.vs 601 d.P = 0.029, logrank test). Multivariate cox regression revealed.neither aspirin nor CCB had.a statistically significant impact on survival when given alone, however in combination the survival benefit was significant; HR = 0.332(CI = 0.126-0.870, P = 0.025). None of the other med.cations showed.a survival benefit in any ***: Aspirin + CCB in combination appears to increase survival in patients with Pd.C, highlighting the potential clinical use of combination therapy to target stromal interactions in pancreatic cancer.

关键词： Pancreatic d.ctal ad.nocarcinoma Stroma Polypharma

Sonic Hed.ehog信号在小脑早期发育中的作用

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南京医科大学学报（自然科学版） 2015年第7期35卷 899-904页

作者：刘晓同李三恩乐珅程雁南京医科大学发育遗传学系江苏南京210029

目的 :研究Sonic Hed.ehog(Shh)信号在小脑发育早期对小脑外颗粒层的颗粒细胞前体(GCP)细胞增殖迁移的影响。方法:通过石蜡切片免疫荧光观察小脑外颗粒层GCP细胞增殖情况;建立体外培养小鼠脑片系统,检测小脑外颗粒层GCP细胞的增殖和动... 详细信息

目的 :研究Sonic Hed.ehog(Shh)信号在小脑发育早期对小脑外颗粒层的颗粒细胞前体(GCP)细胞增殖迁移的影响。方法:通过石蜡切片免疫荧光观察小脑外颗粒层GCP细胞增殖情况;建立体外培养小鼠脑片系统,检测小脑外颗粒层GCP细胞的增殖和动态迁移情况。结果:小鼠出生后7 d.脑外颗粒层增殖的GCP细胞最多;Shh信号通路促进小脑外颗粒层GCP细胞的增殖,用环巴胺(cyclopamine,CPA)抑制信号通路后小脑外颗粒层GCP细胞增殖受到抑制,但迁移不受影响。结论:Shh信号通路是促进小脑外颗粒层细胞增殖及有丝分裂必不可少的一部分,且它的作用只部分局限于外颗粒层。

关键词： Shh信号通路颗粒细胞前体细胞体外培养脑片

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3d.算机图形学基础

3D计算机图形学基础