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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 | Dexamethasone mediates protection against acute pancreatitis via upregulation of pancreatitis-associated proteins显示文摘AIM: To examine the influence of dexamethasone on pancreatitis-associated protein (PAP) gene expression using both in vitro and in vivo models of acute pancreati- tis and to study how PAP gene expression correlates with severity of pancreatitis. METHODS: In vitro, IL-6 stimulated pancreas acinar AR42J cells were cultured with increasing concentrations of dexamethasone and assayed for PAP expression (RT-PCR). In vivo , pancreatitis was induced in rats by retrograde injection of 40 g/L taurocholate into the pancreatic duct. Animals were pretreated with dexamethasone (2 mg/kg) daily or saline for 4 d. Pancreata and serum were harvested after 24 h and gene expression levels of PAPⅠ, Ⅱ and Ⅲ were measured by RT-PCR. Severity of pancreatitis was based on serum amylase, pancreatic wet weight, and histopathological score. RESULTS: In vitro, dexamethasone and IL-6 induced a marked transcription of PAPⅠ, Ⅱ and Ⅲ genes in AR42J cells at 24 h (P < 0.05 for all comparisons). In vivo, pancreas mRNA levels of PAPⅠ, Ⅱ or Ⅲ increased by 2.6-fold, 1.9-fold, and 1.3-fold respectively after dexa- methasone treatment, compared with saline treated ani- mals. Serum amylase levels and edema were significantly lower in the dexamethasone group compared with the saline group. Histopathologic evaluation revealed less inflammation and necrosis in pancreata obtained from dexamethasone treated animals (P < 0.05). CONCLUSION: Dexamethasone significantly decreases the severity of pancreatitis. The protective mechanism ofdexamethasone may be via upregulating PAP gene ex- pression during injury. | Emad Kandil Yin-Yao Lin Martin H Bluth Hong Zhang Gabriel Levi Michael E Zenilman | 2006 | World Journal of Gastroenterology2006，12，42： | 3 |
| 3 | 胆固醇酯转移蛋白基因的蛋白质截断型变异体与冠状动脉性心脏病风险的关系显示文摘随机对照试验结果表明,抑制胆固醇酯转运蛋白(cholesteryl ester transfer protein,CETP)的疗法并不能降低冠状动脉性心脏病(coronary heart disease,CHD)的发生风险。研究失败的可能原因包括靶目标无效、靶目标外小分子的不良反应和随机对照设计因素影响等。在编码药物靶点的基因中具有天然存在的遗传变异,以此为基础,人类研究可以深入了解针对基因产物的治疗的潜在功效和安全性。 | Nomura A Won HH Khera AV Takeuchi F Ito K McCarthy S Emdin CA Klarin D Natarajan P Zekavat SM Gupta N Peloso GM Borecki IB Teslovich TM Asselta R Duga S Merlini PA Correa A Kessler T Wilson JG Bown MJ Hall AS Braund PS Carey DJ Murray MF Kirchner HL Leader JB Lavage DR Manus JN Hartze DN Samani NJ Schunkert H Marrugat J Elosua R McPherson R Farrall M Watkins H Juang JJ Hsiung CA Lin SY Wang JS Tada H Kawashiri MA Inazu A Yamagishi M Katsuya T Nakashima E Nakatochi M Yamamoto K Yokota M Momozawa Y Rotter JI Lander ES Rader DJ Danesh J Ardissino D Gabriel S Willer CJ Abecasis GR Saleheen D Kubo M Kato N Ida Chen YD Dewey FE Kathiresan S 刘莉 叶鹏 | 2017 | 中华高血压杂志2017，25，9： | 2 |
| 4 | Multiwavelength operation of an erbium-doped fiber ring laser using a dual-pass Mach-zehnder comb filter 显示文摘 | Lin X Z Pun E Y B | 1999 | opt Commun1999，169，： | 1 |
| 5 | Reduction of dislocations in GaN epilayers grown on Si(111)substrate using SixNy inserting layer显示文摘 | Lee K J Shin E H Lin K Y | 2004 | Appl Phys Lett2004，85，9： | 1 |
| 6 | Optimization of Separation and Migration Behavior of Cephalosporins in Capillary zone electrophoresis 显示文摘 | Lin C E Chen H w Erick C | 2000 | J Chromatogr A2000，879，2： | 1 |
| 7 | Supercritical fluid extraction of lanthanides and actinides from solid materials with a fluorinated β-diketone显示文摘 | LIN Y H BRAUER R D LAINTZ K E | 1993 | Anal Chem1993，65，18： | 1 |
| 8 | Eradication of small intestinalbacterial overgrowth reduces symptoms of irritable bowel syndrome显示文摘 | PIMENTEL M CHOW E J LIN H C | 2000 | The American Journal of Gastroenterology2000，95，12： | 1 |
| 9 | Seasonal variations and origins of particulate organic carbon in the lower Garonne River at La Re°ole (SW France)显示文摘 | VEYSSY E EIEHEBER H LIN R G | 1999 | Hydrobiologia1999，391，： | 1 |
| 10 | Er^3+-doped Na2O·Cd3Al2Si3O12 glass for infrared and upcoversion applications 显示文摘 | Lin H Pun E Y B Liu X R | 2001 | J Noncryst Solids2001，283，： | 1 |
| 11 | Development of a mechanistic- empirical model to characterize rutting in flexible pavements 显示文摘 | Chen J S Lin C H Stein E | 2004 | Journal of Transportation Engineering2004，130，4： | 1 |
| 12 | Working set selection using the second order information for training SVM显示文摘 | Fan R E Chen P H Lin C J | 2005 | Journal of Machine Learning Research2005，，6： | 1 |
| 13 | Flexural streamwise vibration of gate plates under vortex action 显示文摘 | THANG N D LIN Q H NAUDASCHER E | 1987 | Proc Int on Flow-Induced Vibrations1987，37，2： | 1 |
| 14 | Texture and Chemical Character- istics of Soy Protein Meat Analog Extruded at High Moisture 显示文摘 | Lin S Hsieh F Huff H E | 2000 | Journal of Food Science2000，65，2： | 1 |
| 15 | An efficient, classification-based approach for grouping pen strokes into objects 显示文摘 | Stahovich T F Peterson E J Lin H | 2014 | Computers & Graphics (S0097-8493)2014，42，8： | 1 |
| 16 | Plastic instability in uniaxial tension tests显示文摘 | Lin I H Hirth J P Hart E W | 1981 | Acta Metallurgica1981，29，： | 1 |
| 17 | Enhanced flame retardancy of polypropylene with magnesium hydroxide, melamine and novolac 显示文摘 | Weil E D Lewin M Lin H S | 1998 | JOURNAL OF FIRE SCIENCES1998，16，5： | 1 |
| 18 | Strategies for enantioseparations of catecholamines and structurally related compounds by capillary zone electrophoresis using sulfated β - cyclodextrins as chiral selectors 显示文摘 | LIN C E CHENG H T FANG I J | 2006 | Electrophoresis2006，27，： | 1 |
| 19 | Targeting bone al eviates osteoarthritis in osteopenic mice and modulates cartilage catabolism显示文摘 | Funck-Brentano T Lin H Hay E | | 0，，03： | 1 |
| 20 | Effects of melatonin in experimental stroke mod- els in acute, sub-acute, and chronic stages显示文摘 | Lin H W E J Lee | 2009 | Neuropsychiatric disease and treatment2009，5，： | 1 |
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