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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 |
| 2 | 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 |
| 3 | A unique sequence in the N-terminal regulatory region controls the nuclear localization of KLF8 by cooperating with the C-terminal zinc-fingers显示文摘Kr 眉 p 像像素的因素 8 (KLF8 ) 抄写因素在房间周期前进起一个关键作用, oncogenic 转变,对间充质的转变和侵略上皮。然而,它的原子本地化信号(NLS ) 没被识别。有另外的 KLF monopartite NLS (mNLS ) 和 C2H2 锌手指(ZF ) 的 KLF8 份额,哪个被显示了是为一些另外的 KLF 的 NLS。在这份报告,用指导 PCR 的 mutagenesis 和 immunofluorescent 显微镜学,我们显示出 mNLSs,任何单个 ZF 的删除,或变化的那混乱 Zn2+ 有约束力或联系 DNA 主题没影响 KLF8 的原子本地化。删除 > 然而,从 C 终点的 1.5 ZF 引起了 KLF8 的细胞质的累积。令人惊讶地,氨基酸(aa ) 的删除 151-200 区域几乎从原子核消除了 KLF8。有 PKC 禁止者的 S165A, K171E 或 K171R 变化,或处理导致了部分细胞质的累积。Co-immunoprecipitation 证明 KLF8 与 importin- 交往了,这个相互作用要求了 ZF 主题。aa 1-150 或 201-261 区域的删除独自没改变原子本地化。BrdU 加入和 cyclin D1 倡导者酶试金作为野类型的 KLF8 证明在原子本地化的 KLF8 异种有缺陷者不能支持 DNA 合成或 cyclin D1 倡导者激活。一起拿,这些结果建议 KLF8 有二 NLS,一包围 S165 和 K171 并且另外的是二双人脚踏车 ZF,它为 KLF8 原子本地化和它的细胞的功能的规定是批评的。 | Tina S Mehta Heng Lu Xianhui Wang Alison M Urvalek Kim-Hang H Nguyen Farah Monzur Jojo D Hammond Jameson Q Ma Jihe Zhao | 2009 | Cell Research2009，19，9： | 10 |
| 4 | Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density显示文摘 | W.S Simonet D.L Lacey C.R Dunstan M Kelley M.-S Chang R Lüthy H.Q Nguyen S Wooden L Bennett T Boone G Shimamoto M DeRose R Elliott A Colombero H.-L Tan G Trail J Sullivan E Davy N Bucay L Renshaw-Gegg T.M Hughes D Hill W Pattison P Campbell S Sander G Van | 1997 | Cell1997，，2： | 6 |
| 5 | A Rapid and Cost-Effective Method for Genotyping Genome-Edited Animals:A Heteroduplex Mobility Assay Using Microfluidic Capillary Electrophoresis显示文摘The recent emergence and application of engineered endonucleases have led to the development of genome editing tools capable of rapidly implementing various targeted genome editions in a wide range of species.Moreover,these novel tools have become easier to use and have resulted in a great increase of applications.Whilst gene knockout(KO) or knockin(KI) animal models are relatively easy to achieve,there is a bottleneck in the detection and analysis of these mutations.Although several methods exist to detect these targeted mutations,we developed a heteroduplex mobility assay on an automated microfluidic capillary electrophoresis system named HMA-CE in order to accelerate the genotyping process.The HMA-CE method uses a simple PCR amplification of genomic DNA(gDNA) followed by an automated capillary electrophoresis step which reveals a heteroduplexes(HD) signature for each mutation.This allows efficient discrimination of wild-type and genome-edited animals down to the single base pair level. | Vanessa Chenouard Lucas Brusselle Jean-Marie Heslan Séverine Remy Séverine Ménoret Claire Usal Laure-Hélène Ouisse Tuan Huy NGuyen Ignacio Anegon Laurent Tesson | 2016 | Journal of Genetics and Genomics2016，43，5： | 4 |
| 6 | Atypical causes of cholestasis显示文摘Cholestatic liver disease consists of a variety of disorders.Primary sclerosing cholangitis and primary biliary cirrhosis are the most commonly recognized cholestatic liver disease in the adult population,while biliary atresia and Alagille syndrome are commonly recognized in the pediatric population.In infants,the causes are usually congenital or inherited.Even though jaundice is a hallmark of cholestasis,it is not always seen in adult patients with chronic liver disease.Patients can have'silent'progressive cholestatic liver disease for years prior to development of symptoms such as jaundice and pruritus.In this review,we will discuss some of the atypical causes of cholestatic liver disease such as benign recurrent intrahepatic cholestasis,progressive familial intrahepatic cholestasis,Alagille Syndrome,biliary atresia,total parenteral nutrition induced cholestasis and cholestasis secondary to drug induced liver injury. | Ken D Nguyen Vinay Sundaram Walid S Ayoub | 2014 | World Journal of Gastroenterology2014，20，28： | 2 |
| 7 | Non-occlusive mesenteric ischemia: Diagnostic challenges and perspectives in the era of artificial intelligence显示文摘Acute mesenteric ischemia(AMI)is a severe condition associated with poor prognosis,ultimately leading to death due to multiorgan failure.Several mechanisms may lead to AMI,and non-occlusive mesenteric ischemia(NOMI)represents a particular form of AMI.NOMI is prevalent in intensive care units in critically ill patients.In NOMI management,promptness and accuracy of diagnosis are paramount to achieve decisive treatment,but the last decades have been marked by failure to improve NOMI prognosis,due to lack of tools to detect this condition.While real-life diagnostic management relies on a combination of physical examination,several biomarkers,imaging,and endoscopy to detect the possibility of several grades of NOMI,research studies only focus on a few elements at a time.In the era of artificial intelligence(AI),which can aggregate thousands of variables in complex longitudinal models,the prospect of achieving accurate diagnosis through machine-learning-based algorithms may be sought.In the following work,we bring you a state-of-the-art literature review regarding NOMI,its presentation,its mechanics,and the pitfalls of routine work-up diagnostic exams including biomarkers,imaging,and endoscopy,we raise the perspectives of new biomarker exams,and finally we discuss what AI may add to the field,after summarizing what this technique encompasses. | Simon Bourcier Julian Klug Lee S Nguyen | 2021 | World Journal of Gastroenterology2021，27，26： | 2 |
| 8 | Early goal-directed therapy in the treatment of severe sepsis and septic shock显示文摘 | Rivers E Nguyen B Havstad S | | 0，，19： | 2 |
| 9 | A toxicity testing protocol using a bioluminescent reporter bacterium from activated sludge显示文摘 | Lajoie C A Lin S C Nguyen H | 2002 | Journal of Microbiological Methods2002，50，3： | 2 |
| 10 | 生理性线粒体破碎是心脏适应能量需求增加的正常现象显示文摘线粒体在心脏中起着双重作用:负责满足能量需求和调节细胞凋亡。通常认为,线粒体的分裂和碎裂是病理性应激(如缺血)的结果,是线粒体质量差的指标,并导致线粒体自噬和细胞死亡。然而,最近的研究表明,抑制裂变也导致线粒体功能减弱和心脏损害,说明裂变对维持心脏和线粒体生物能量平衡十分重要。 | 刘莉 叶鹏 Coronado M Fajardo G Nguyen K Zhao M Kooiker KB Jung G Hu DQ Reddy S Sandoval E Stotland A Gottlieb RA Bernstein D | 2018 | 中华高血压杂志2018，26，1： | 2 |
| 11 | T - cell tolerance or function is determined by combinatorial costimulatory signals显示文摘 | Nurieva R Thomas S Nguyen T | 2006 | EMBO J2006，25，11： | 1 |
| 12 | E1A- induced processing of procaspase - 8 can occur independently of FADD and is inhibited by Bcl-2显示文摘 | Nguyen M Branton PE Roy S | 1998 | J Biol Chem1998，273，33： | 1 |
| 13 | Autophagy and angiogenesis inhibition 显示文摘 | Ramakrishman S Nguyen TM Subramanian IV | 2007 | Autophagy2007，3，5： | 1 |
| 14 | Activation of cellular invasion by trefoil peptides and src is mediated by cyclooxygenase-2 and thromboxane A2 receptor-dependent signaling pathways显示文摘 | Rodrigues S Nguyen QD Faivre S | 2001 | FASEB J2001，15，9： | 1 |
| 15 | Random subspace two-dimensional PCA for face recognition显示文摘 | Nguyen N Liu W Venkates S | 2002 | Lecture notes in computer science2002，4810，： | 1 |
| 16 | Hydrodynamics and volumetric gas-liquid mass transfer coefficient of astirred vessel equipped with a gas inducing impeller 显示文摘 | PONCIN S NGUYEN C MIDOUX N | 2002 | Chemical Engineering Science2002，57，16： | 1 |
| 17 | Hypothalamic hamartomas:seven cases and review of the literature显示文摘 | Nguyen D Singh S Zaatreh M | 2003 | Epilepsy Behav2003，4，3： | 1 |
| 18 | Early goal- directed therapy in the treatment of severe sepsis and septic shock显示文摘 | Rivers E Nguyen B Havstad S | 2001 | N Engl J Med2001，345，19： | 1 |
| 19 | Effect of timolol betaxolol,and levobunolol on human Tenon' s fibroblasts in tissue culture 显示文摘 | Williams DE Nguyen KD Shapourifar-Tehrani S | | Invest Ophthahnol Vis Sci0，33，： | 1 |
| 20 | Early goal-directed therapy inthe treatment of severe sepsis and septic shock 显示文摘 | Rivers E Nguyen B Havstad S | 2001 | N Engl J Med2001，345，： | 1 |
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