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1帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析显示文摘背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PEMBRO-RT研究和Ⅰ/Ⅱ期MDACC研究中,患有转移性非小细胞肺癌(NSCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NSCLC患者的免疫治疗应答。方法PEMBRO-RT和MDACC研究纳入标准:患者年龄≥18岁,患有转移性NSCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PEMBRO-RT研究纳入曾接受过化疗患者,MDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PEMBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为<10年组和≥10年组)。MDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PEMBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在MDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFS)和总生存期(OS)。2个研究的意向治疗(ITT)人群均纳入分析。PEMBRO-RT研究(NCT02492568)和MDACC研究(NCT02444741)均在ClinicalTrials.gov上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFS中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;OS中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NSCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。陈大卫(翻译) 于金明(校对) Willemijn S M E Theelen Vivek Verma Brian P Hobbs Heike M U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia M de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoulidis Steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh 2021中华肿瘤防治杂志2021,28,24:49
2AGNP精神科治疗药物监测共识指南:2011显示文摘治疗药物监测(Therapeutic drug monitoring,TDM),如通过定量测定血清或血浆药物浓度指导用药剂量优化,已经成为对患者进行精神药物治疗的很有价值的工具。在患者用药依从性难以判断、药物耐受性不佳、治疗剂量下无效以及可能存在药代动力学药物-药物相互作用等情况下,测定药物浓度是很有用的。在精神科,有可能明显获益于TDM的主要患者群体包括儿童、孕妇、老年患者、智力障碍患者、涉及司法的患者、已知或怀疑携带药代动力学相关基因变异的患者,以及合并躯体疾病影响药代动力学的患者。然而,只有将TDM充分整合到临床治疗过程中去,才能发挥其优化药物治疗的潜在优势。为了促进TDM的合理应用,神经精神药理学与药物精神病学协会(Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie,AGNP)的TDM专家组在2004年发表了精神药物治疗药物监测指南。之后,随着知识不断更新,又有许多可能需要进行TDM的新药上市。因此,本次更新将神经精神药物的种类扩展到了128种,并将其TDM必要性划分为从'强烈推荐'到'可能有用'的四个等级。经过大量细致且全面的文献检索与分门别类的汇总整理,将基于循证医学理念的'治疗参考浓度范围'和'剂量相关参考浓度范围'呈现给大家。本共识指南引入了'实验室警戒浓度'的新概念,即实验室需要马上告知治疗医生的药物浓度上限。本共识指南还给出了诸如药物作为细胞色素P450酶的底物和抑制剂的性质,代谢物与母药浓度比值的常见范围,以及与结果解释相关的内容,还提供了何时将TDM与遗传药理学检测相结合的建议。遵循本指南,有助于改善许多患者精神药物治疗的效果,特别是那些存在药代动力学异常的患者。TDM是一门交叉学科,有时针对看起来不一致的数据,需要多学科坦诚地讨论,只有这样,患者才能从这种合作中获益。Hiemke C Baumann P Bergemann N Conca A Dietmaier O Egberts K Fric M Gerlach M Greiner C Gründer G Haen E Havemann-Reinecke U Jaquenoud Sirot E Kirchherr H Laux G Lutz UC Messer T Müller MJ Pfuhlmann B Rambeck B Riederer P Schoppek B Stingl J Uhr M Ulrich S Waschgler R Zernig G 李文标(译) 果伟(译) 阮灿军(译) 贺静(译) 汤宜朗(审校) 王传跃(审校) 2016实用药物与临床2016,19,10:37
3最新AD研究用诊断标准:IWG-2标准显示文摘在过去的8年中,国际工作组织(IWG)和美国国立老化研究院-阿尔茨海默协会(NIA-AA)建立了阿尔茨海默病(AD)诊断标准,它能更好地定义AD的临床表型,整合了生物标记物于诊断流程中,并覆盖了疾病的全程。本意见书充分地权衡了IWG标准的优缺点,建议改进诊断框架。依据这些改进,AD的诊断变得简单,只要有恰当的AD临床表型(典型或不典型)和与AD的病理相一致的病理生理学生物标志物出现。我们认为疾病的下游的定位性生物标志,如容积性磁共振成像(MRI)和氟脱氧葡萄糖-正电子发射型计算机断层成像(FDG-PET)等,适合更好地测量和监测疾病过程。本文还详述了非典型性AD、混合性AD和AD临床前期的特异诊断标准。陈刚 曹雯炜 俞羚 糜建华 Dubois B Feldman HH Jacova C Hampel H Molinuevo JL Blennow K DeK osky ST Gauthier S Selkoe D Bateman R Cappa S Crutch S Engelborghs S Frisoni GB Fox NC Galasko D Habert MO Jicha GA Nordberg A Pasquier F Rabinovici G Robert P Rowe C Salloway S Sarazin M Epelbaum S de Souza LC Vellas B Visser PJ Schneider L Stern Y Scheltens P Cummings JL 2014神经病学与神经康复学杂志2014,11,3:31
4一项中断时间序列研究与集群随机试验:减少耐药细菌在重症监护室中定植和传播的干预措施显示文摘背景 重症监护室(ICU)是耐药细菌传播的高危科室,在设置标准预防措施时缺乏对"全面筛查和隔离携带或感染耐药细菌者"效果评估的对照研究,本研究评估此干预措施对减少ICU中耐药细菌的定植与传播的效果.曾翠 吴安华 Derde L P G Cooper B S Goossens H 2014中国感染控制杂志2014,13,1:23
5世界卫生组织(WHO)造血与淋巴组织肿瘤分类方案:临床顾问委员会会议报告显示文摘引言 :从 1995年开始 ,欧洲病理学工作者协会和血液病理学会一直致力于制定一个新的世界卫生组织 (WHO)血液恶性肿瘤分类方案 ,该分类方案包括淋巴系肿瘤、髓系肿瘤、组织细胞肿瘤和肥大细胞肿瘤。 材料与方法 :此项 WHO计划共组成十个病理学工作者委员会 ,负责确定病种和作出定义。另外还成立一个由国际血液学家和肿瘤学家组成的临床顾问委员会 (CAC)以保证该分类的临床实用性。 1997年 11月召开会议讨论了与该分类有关的临床问题。 结果 :WHO采纳了 1994年国际淋巴瘤研究组 (IL SG)报告的修订欧美淋巴系肿瘤分类 (REAL)方案作为淋巴系肿瘤的分类方案。该方案的分类方法遵循以下原则 :分类应是联合应用形态学、免疫表型、遗传特征及临床特征能够清楚界定的“真实存在”(“real”)病种的名录 ,上述各项特征的相对重要性因病种不同而异 ,不存在任何“金标准”。 WHO将 REAL分类原则延用于髓系肿瘤和组织细胞肿瘤 ,髓系肿瘤的分类包括联合应用细胞形态学和细胞遗传学异常能够界定的各个病种。围绕一系列临床问题召集的这次 CAC会议 ,就提交的大多数问题达成共识 ,这些问题及共识将详述于下。对于另外一些问题 ,CAC认为淋巴系肿瘤临床分组既无必要也不必需 ,患者的治疗取决于淋巴瘤的具体类型 ,如有?N L Harris E S Jaffe J Diebold G Flandrin H K Muller-Hermelink J Vardiman T A Lister C D Bloomfield 张凤奎 郝玉书 2001白血病.淋巴瘤2001,10,3:20
6血管性认知障碍的诊断标准:国际血管性行为与认知障碍学会的申明显示文摘长期以来,脑血管病(CVD)就被认为是认知损害的一个重要原因,但是有关脑血管病后认知障碍的概念化却有着一段多变的历史。'动脉变硬'或脑的动脉粥样硬化是'老化'的原因,是存在已久的观点,在20世纪60年代受到了来自英格兰纽卡斯尔的神经病理学研究的质疑。这些研究表明,血管性痴呆(vascular dementia,Va D)与超过一定程度的多发性脑梗死有关。徐岩 郭起浩 Sachdev P Kalaria R O'Brien J Skoog I Alladi S Black SE Blacker D Blazer DG Chen C Chui H Ganguli M Jellinger K Jeste DV Pasquier F Paulsen J Prins N Rockwood K Roman G Scheltens P 2014神经病学与神经康复学杂志2014,11,3:19
7高危患者目标血压与心血管病预后显示文摘指南推荐血压目标值应〈140/90 mmHg(1mmHg=0.133kPa)以减少心血管事件的发生。但与其他心血管病预后(如冠状动脉事件)相比,包括脑卒中及心力衰竭在内的心血管病预后与收缩压下降关系更密切。一些心血管事件(如冠状动脉事件)风险在收缩压低时亦增高,风险-收缩压关系呈J形曲线,而脑卒中与血压不是J形曲线关系。B?hm M Schumacher H Teo KK Lonn EM Mahfoud F Mann JF Mancia G Redon J Schmieder RE Sliwa K Weber MA Williams BYusuf S 曲浥晨 叶鹏 2017中华高血压杂志2017,25,6:14
8内脏脂肪组织通过产生骨桥蛋白调控成纤维细胞衰老促进心脏衰老显示文摘老化通过增加包括骨桥蛋白(osteopontin,OPN)在内的细胞外基质(extracellular matrix,ECM)蛋白的沉积引起心脏结构和功能改变进而导致进行性间质纤维化。虽然已知OPN参与各种病理状况,但其在心肌衰老中的作用仍不清楚。Sawaki D Czibik G Pini M Ternacle J Suffee N Mercedes R Marcelin G Surenaud M Marcos E Gual P Clément K Hue S Adnot S Hatem SN Tsuchimochi I Yoshimitsu T Hénégar C Derumeaux G 刘青 叶鹏 2018中华高血压杂志2018,26,3:14
9国际胃袖状切除专家共识:基于>12000手术病例的最佳操作指南显示文摘腹腔镜胃袖状切除术(1aparoscopic sleeve gastrectomy,LSG)系相对较新的减重手术方式。因其操作相对简单、治疗肥胖合并疾病及减重效果明显,逐步得以广泛接受。目前美国代谢与减重手术协会将其推荐为肥胖症治疗的单独标准术式。2011年3月25~26日,苏远涛 徐安安 朱江帆 Diaz AA Arvidsson D Baker RS Basso N Bellanger D Boza C El Mourad H France M Gagner M Galvao-Neto M Higa KD Himpens J Hutchinson CM Jacobs M Jorgensen JO Jossart G Lakdawala M Nguyen NT Nocca D Prager G Pomp A Ramos AC Rosenthal RJ Shah S Vix M Wittgrove A Zundel N 2013中国微创外科杂志2013,13,9:12
10Effects of Austempering and Martempering Processes on Amount of Retained Austenite in Cr-Mo Steels (FMU-226) Used in Mill Liner显示文摘The presence of retained austenite gives rise to deterioration of the wear resistance and fracture strength of Cr-Mo steels in many cases. Thus, the effects of heat treatments including direct quenching, martempering, and austempering on the retained austenite existing in the microstructure of these steels were investigated. Specimens were austenized at 950 ℃ followed by direct quenching using compressed and still air. The specimens were also isothermally quenched in salt bath at 200 and 300 ℃ for 2, 8, 30, and 120 min. Microstructures of the specimens were studied using optical microscope (traditional black and white etching as well as color etching), scanning electron microscope (SEM), microhardness tester, and X-ray diffraction (XRD). The results showed that the lowest amount of retained austenite in the microstructure was obtained in the specimens quenched isothermally at 300 ℃ for 120 min.M H Shaeri H Saghafian S G Shabestari 2010Journal of Iron and Steel Research(International)2010,17,2:8
11急性脊髓损伤患者治疗的临床操作指南:关于MRI基线在临床治疗决策与结果预测中作用的几点建议(英文)显示文摘The objective of this guideline is to outline the role of magnetic resonance imaging(MRI) in clinical decision making and outcome prediction in patients with traumatic spinal cord injury(SCI).Methods A systematic review of the literature was conducted to address key questions related to the use of MRI in patients with traumatic SCI.This review focused on longitudinal studies that controlled for baseline neurologic status.A multidisciplinary Guideline Development Group(GDG) used this information,their clinical expertise,and patient input to develop recommendations on the use of MRI for SCI patients.Based on GRADE(Grading of Recommendation,Assessment,Development and Evaluation),a strong recommendation is worded as ' we recommend,' whereas a weaker recommendation is indicated by 'we suggest.' Results Based on the limited available evidence and the clinical expertise of the GDG,our recommendations were:(1) 'We suggest that MRI be performed in adult patients with acute SCI prior to surgical intervention,when feasible,to facilitate improved clinical decision-making'(quality of evidence,very low) and(2) 'We suggest that MRI should be performed in adult patients in the acute period following SCI,before or after surgical intervention,to improve prediction of neurologic outcome '(quality of evidence,low).Conclusions These guidelines should be implemented into clinical practice to improve outcomes and prognostication for patients with SCI.Fehlings MG Martin AR Tetreault LA Aarabi B Anderson P Arnold PM Brodke D Burns AS Chiba K Dettori JR Furlan JC Hawryluk G Holly LT Howley S Jeji T Kalsi-Ryan S Kotter M Kurpad S Kwon BK Marino RJ Massicotte E Merli G Middleton JW Nakashima H Nagoshi N Palmieri K Singh A Skelly AC Tsai EC Vaccaro A Wilson JR Yee A Harrop JS 2017中华神经外科疾病研究杂志2017,16,6:8
12原发灶切除在无症状的、同时性的、转移灶不可切除的结直肠癌患者中的作用:一项多中心随机对照试验显示文摘目的:我们在同时性的、转移灶不可切除的无症状Ⅳ期结直肠癌患者中,评估接受原发灶切除术(primary tumor resection,PTR)续贯化疗的患者相比接受单纯化疗的患者的生存优势。方法:这是一项开放的前瞻性随机对照试验(ClnicalTrials.gov注册号:NCT01978249)。从2013年5月至2016年4月,在12所三级医院中将48例诊断为转移灶不可切除的、原发灶无症状的结直肠癌患者按1:1比例进行随机化分组,其中PTR组26例、化疗组22例。主要终点是两年总生存率,次要终点为与原发灶、PTR相关的并发症发生率以及转变为可切除状态的转化率。卓长华 陈功 PARK E J BAEK J H CHOI G S 2020结直肠肛门外科2020,26,5:8
134-1BB signaling activates glucose and fatty acid metabolism to enhance CD8^(+) T cell proliferation显示文摘4-1BB(CD137)is a strong enhancer of the proliferation of CD8^(+)T cells.Since these cells require increased production of energy and biomass to support their proliferation,we hypothesized that 4-1BB signaling activated glucose and fatty acid metabolism.We found that treatment with agonistic anti-4-1BB mAb promoted the proliferation of CD8^(+)T cells in vitro,increasing their size and granularity.Studies with a glycolysis inhibitor and a fatty acid oxidation inhibitor revealed that CD8^(+)T cell proliferation required both glucose and fatty acid metabolism.Anti-4-1BB treatment increased glucose transporter 1 expression and activated the liver kinase B1(LKB1)-AMP-activated protein kinase(AMPK)-acetyl-CoA carboxylase(ACC)signaling pathway,which may be responsible for activating the metabolism of glucose and fatty acids.We also examined whether blocking glucose or fatty acid metabolism affected cell cycle progression and the anti-apoptotic effect of 4-1BB signaling.The increase of anti-apoptotic factors and cyclins in response to anti-4-1BB treatment was completely prevented by treating CD8^(+)T cells with the fatty acid oxidation inhibitor,etomoxir,but not with the glycolysis inhibitor,2-deoxy-D-glucose.We conclude that anti-4-1BB treatment activates glucose and fatty acid metabolism thus supporting the increased demand for energy and biomass,and that fatty acid metabolism plays a crucial role in enhancing the cell cycle progression of anti-CD3-activated CD8^(+)T cells in vitro and the anti-apoptotic effects of 4-1BB signaling on these cells.Beom K Choi Do Y Lee Don G Lee Young H Kim Seon-Hee Kim Ho S Oh Chungyong Han Byoung S Kwon 2017Cellular & Molecular Immunology2017,14,9:6
14中心和外周动脉脉搏波传导速度测量的重复性:社区动脉粥样硬化风险研究显示文摘通过脉搏波传导速度(pulsewavevelocity,PwV)检测动脉硬化程度是当前对高血压和心血管病风险评估和分层所日渐常用的方式。颈股动脉脉搏波传导速度(catroidfemoralarteryPWV,cfPWV)是一项公认的测定中心动脉硬化程度的方式。Meyer ML Tanaka H Palta P Patel MD Camplain R Couper D Cheng S Al Qunaibet A Poon AK Heiss G 陈云 叶鹏 2016中华高血压杂志2016,24,5:6
15应用微型机器人装置对难治性癫痫患者进行脑深部电极植入(英文)显示文摘Dorfer C Minchev G Czech T Stefanits H Feucht M Pataraia E Baumgartner C Kronreif G Wolfsberger S 2016中华神经外科疾病研究杂志2016,15,4:5
16Coagonist of glucagon-like peptide-1 and glucagon receptors ameliorates kidney injury in murine models of obesity and diabetes mellitus显示文摘AIM To investigate the role of glucagon-like peptide-1(GLP-1)/glucagon receptors coagonist on renal dysfunction associated with diabetes and obesity. METHODS Chronic high-fat diet fed C57 BL/6 J mice, streptozotocintreated high-fat diet fed C57 BL/6 J mice and diabeticC57 BLKS/J db/db mice were used as models of diabetes-induced renal dysfunction. The streptozotocintreated high-fat diet fed mice and db/db mice were treated with the GLP-1 and glucagon receptors coagonist(Aib2 C24 Chimera2, 150 μg/kg, sc) for twelve weeks, while in chronic high-fat diet fed mice, coagonist(Aib2 C24 Chimera2, 150 μg/kg, sc) treatment was continued for forty weeks. Kidney function, histology, fibrosis, inflammation, and plasma biochemistry were assessed at the end of the treatment. RESULTS Coagonist treatment decreased body weight, plasma lipids, insulin resistance, creatinine, blood urea nitrogen, urinary albumin excretion rate and renal lipids. In kidney, expression of lipogenic genes(SREBP-1 C, FAS, and SCD-1) was decreased, and expression of genes involved in β-oxidation(CPT-1 and PPAR-α) was increased due to coagonist treatment. In plasma, coagonist treatment increased adiponectin and FGF21 and decreased IL-6 and TNF-?. Coagonist treatment reduced expression of inflammatory(TNF-α, MCP-1, and MMP-9) and pro-fibrotic(TGF-β, COL1 A1, and α-SMA) genes and also improved histological derangement in renal tissue.CONCLUSION Coagonist of GLP-1 and glucagon receptors alleviated diabetes and obesity-induced renal dysfunction by reducing glucose intolerance, obesity, and hyperlipidemia.Vishal J Patel Amit A Joharapurkar Samadhan G Kshirsagar Brijesh K Sutariya Maulik S Patel Hiren M Patel Dheerendra K Pandey Rajesh H Bahekar Mukul R Jain 2018World Journal of Diabetes2018,9,6:5
17Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models显示文摘AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD).Nicha Wongjarupong Gabriela M Negron-Ocasio Roongruedee Chaiteerakij Benyam D Addissie Essa A Mohamed Kristin C Mara William S Harmsen J Paul Theobald Brian E Peters Joseph G Balsanek Melissa M Ward Nasra H Giama Sudhakar K Venkatesh Denise M Harnois Michael R Charlton Hiroyuki Yamada Alicia Algeciras-Schimnich Melissa R Snyder Terry M Therneau Lewis R Roberts 2018World Journal of Gastroenterology2018,24,12:5
18健康领域的文化能力显示文摘1背景 尽管人类对其他社会的兴趣纵贯历史的各个阶段,但是检验不同文化概念对人类健康实践的影响从20世纪才开始,当时是伴随着长期的人类学田野调查产生的,这些田野调查揭露了不同文化之间相关卫生实践的多样性、复杂性和连续性。Napier A D Ancarno C Butler B Calabrese j Chater A Chatterjee H Guesnet F Home R Jacyna S Jadhav S Macdonald A Neuendorf U Parkhurst A Reynolds R Scambler G Shamdasani S Smith S Z Stougaard-Nielsen J Thomson L Tyler N Volkmann A M Walker T Watson J Williams AC Willott C Wilson J Woolf K 2016中国卫生政策研究2016,9,2:5
19Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial显示文摘Eric Lawitz Fred F Poordad Phillip S Pang Robert H Hyland Xiao Ding Hongmei Mo William T Symonds John G McHutchison Fernando E Membreno 2013The Lancet2013,,:5
20Association between low molecular polypeptide 7 single nucleotide polymorphism and response to therapy in hepatitis C virus infection显示文摘AIM: To investigate the relationship between low molecular polypeptide-7 (LMP-7) gene polymorphism and response to interferon (IFN) therapy in chronic hepatitis C virus (HCV) patients. METHODS: LMP-7 polymorphism at codon 49 with nucleotide substitution from A to C was amplified in 104 chronic HCV patients of genotype 4. The amplicons were digested with restriction endonuclease Bsm I and the produced restriction fragment length polymorphism was analyzed. Patients received IFN + regional blood volume therapy for 48 wk and the frequency of thissingle nucleotide polymorphism (SNP) was statistically correlated with treatment response. The exclusion criteria for these patients were stated by the national health program for treating viral hepatitis. Main exclusion criteria included co-infection with hepatitis B virus or schistosomiasis, thyroid dysfunction, uncontrolled diabetes mellitus, history of long term drug or alcohol intake and autoimmune hepatitis. Multivariate analyses were done to correlate LMP-7 SNP plus several factors such as age, gender, weight, serum alpha-fetoprotein (AFP) and alanine aminotransferase levels, liver activity, fibrosis score and viral load with response to therapy. RESULTS: The data presented in this study clearly demonstrated statistically significant differences between sustained virological response (SVR) (defined as the absence of HCV RNA levels in the patient's sera at least 6 mo after discontinuation of treatment) and non-response (NR) (where HCV RNA levels in the patient's sera never become undetectable for 6 mo during or after treatment). Variables were described as odds ratio with 95%CI. The data were considered significant if P values were ≤ 0.05; highly significant if P < 0.01 and very highly significant if P < 0.001. Current data showed that 91.7% of patients carrying LMP-7 C/C allele were associated with SVR, while the other two genotypes C/A and A/A were associated with NR patients, 83.3% and 64.3% respectively, showing that genotype CC was strongly associated with response to interferon (95%CI: 12.0719-134.6572, P = 0.0001). The majority of parameters recorded in SVR and NR patients included higher values of mean age (P = 0.004), alanine aminotransferase (P = 0.001), AFP (P = 0.001), body weight (P = 0.025), viral load (P = 0.025), higher fibrosis and histological activity index indices among NR vs SVR patients. Also, the multivariate statistical analysis of the different factors of fibro-sis score, liver activity grade, genotypes and alleles of LMP-7 gene polymorphism in responders and NRs of HCV patients in this study showed that HCV patients with A allele had a very highly significant association with the NRs, high fibrosis and higher liver activity, while the C allele had a very highly significant association with the responders, low fibrosis and lower liver activity (95%CI: 3.5800-13.2519, P = 0.0001).CONCLUSION: LMP-7 SNP is a candidate gene that should be considered when designing a mathematical model for predicting response to therapy and disease progression in HCV patients.Moataza H Omran Basma E Fotouh Samar S Youssef Noha E Ibrahim Wael Nabil EL-Sayed M Mahdy Wafaa G Shosha Mostafa K El-Awady 2013World Journal of Hepatology2013,5,3:4
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