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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 | Different risk factors influence peptic ulcer disease development in a Brazilian population显示文摘AIM: To investigate age, sex, histopathology and Helicobacter pylori (H. pylori) status, as risk factors for gastroduodenal disease outcome in Brazilian dyspeptic patients.tients submitted to upper gastroscopy at Hospital das Clinicas of Marilia, antral biopsy specimens were obtained and subjected to histopathology and H. pylori diagnosis. All patients presenting chronic gastritis (CG) and peptic ulcer (PU) disease localized in the stomach, gastric ulcer (GU) and/or duodenal ulcer (DU) were included in the study. Gastric biopsies (n = 668) positive for H. pylori by rapid urease test were investigated for vacuolating cytotoxin A (vacA ) medium (m) region mosaicism by polymerase chain reaction. Logistic regression analysis was performed to verify the association of age, sex, histopathologic alterations, H. pylori diagnosis and vacA m region mosaicism with the incidence of DU, GU and CG in patients. RESULTS: Of 1466 patients submitted to endoscopy, 1060 (72.3%) presented CG [male/female = 506/554; mean age (year) ± SD = 51.2 ± 17.81], 88 (6.0%) presented DU [male/female = 54/34; mean age (year) ± SD = 51.4 ± 17.14], and 75 (5.1%) presented GU [male/female = 54/21; mean age (year) ± SD = 51.3 ± 17.12] and were included in the comparative analysis. Sex and age showed no detectable effect on CG incidence (overall c 2 = 2.1, P = 0.3423). Sex [Odds ratios (OR) = 1.8631, P = 0.0058] but not age (OR = 0.9929, P = 0.2699) was associated with DU and both parameters had a highly significant effect on GU (overall c 2 = 30.5, P < 0.0001). The histopathological results showed a significant contribution of ageing for both atrophy (OR = 1.0297, P < 0.0001) and intestinal metaplasia (OR = 1.0520, P < 0.0001). Presence of H. pylori was significantly associated with decreasing age (OR = 0.9827, P < 0.0001) and with the incidence of DU (OR = 3.6077, P < 0.0001). The prevalence of m1 in DU was statistically significant (OR = 2.3563, P = 0.0018) but not in CG (OR = 2.678, P = 0.0863) and GU (OR = 1.520, P = 0.2863). CONCLUSION: In our population, male gender was a risk factor for PU; ageing for GU, atrophy and metapla-sia; and H. pylori of vacA m1 genotype for DU. | Rodrigo Buzinaro Suzuki Rodrigo Faria Cola Larissa Tranquilino Bardela Cola Camila Garcia Ferrari Fred Ellinger Altino Luiz Therezo Luis Carlos da Silva André Eterovic Márcia Aparecida Sperana | 2012 | World Journal of Gastroenterology2012，18，38： | 8 |
| 3 | Three-dimensional perfused human in vitro model of nonalcoholic fatty liver disease显示文摘AIM To develop a human in vitro model of non-alcoholic fatty liver disease(NAFLD), utilising primary hepatocytes cultured in a three-dimensional(3D) perfused platform. METHODS Fat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids(FFA) from culture medium was monitored. Hepatic functions, gene expression profiles and adipokine release were compared for cells cultured in fat and lean conditions. To determine if fat loading in the system could be modulated hepatocytes were treated with known anti-steatotic compounds. RESULTS Hepatocytes cultured in fat medium were found to accumulate three times more fat than lean cells and fat uptake was continuous over a 14-d culture. Fat loading of hepatocytes did not cause any hepatotoxicity and significantly increased albumin production. Numerous adipokines were expressed by fatty cells and genes associated with NAFLD and liver disease were upregulated including: Insulin-like growth factorbinding protein 1, fatty acid-binding protein 3 and CYP7A1. The metabolic activity of hepatocytes cultured in fatty conditions was found to be impaired and the activities of CYP3A4 and CYP2C9 were significantlyreduced, similar to observations made in NAFLD patients. The utility of the model for drug screening was demonstrated by measuring the effects of known antisteatotic compounds. Hepatocytes, cultured under fatty conditions and treated with metformin, had a reduced cellular fat content compared to untreated controls and consumed less FFA from cell culture medium.CONCLUSION The 3D in vitro NAFLD model recapitulates many features of clinical NAFLD and is an ideal tool for analysing the efficacy of anti-steatotic compounds. | Tomasz Kostrzewski Terri Cornforth Sophie A Snow Larissa Ouro-Gnao Cliff Rowe Emma M Large David J Hughes | 2017 | World Journal of Gastroenterology2017，23，2： | 6 |
| 4 | Spontaneous elimination of hepatitis C virus infection: A retrospective study on demographic, clinical, and serological correlates显示文摘AIM: To fi nd correlates to spontaneous clearance of hepatitis C virus (HCV) infection, this study compared individuals with self-limited and chronic infection with regard to clinical, demographic, and serological pa-rameters. METHODS: Sixty-seven anti-HCV positive and repeatedly HCV RNA negative individuals were considered to have resolved HCV infection spontaneously. To determine the viral genotype these patients had been infected with HCV serotyping was performed. For comparison reasons, 62 consecutive patients with chronic hepatitis C were enrolled. Cases and controls were compared stratifi ed for age and sex. RESULTS: Retrospective analysis showed (1) a lower humoral reactivity to HCV in patients with self-limited compared to chronic HCV-infection and (2) that younger age, history of iv drug use, and acute/post-acute hepatitis A or B co-infections, but not viral genotypes, are independent correlates for spontaneous HCV clearance. CONCLUSION: The stronger humoral reactivity to HCV in patients with persistent infections and in those with a history of iv drug use is supposed to be due to continuous or repeated contact(s) to the antigen. Metachronous hepatitis A or hepatitis B infections might favor HCV clearance. | Perdita Wietzke-Braun Larissa Bettina Mnhardt Albert Rosenberger Angela Uy Giuliano Ramadori Sabine Mihm | 2007 | World Journal of Gastroenterology2007，13，31： | 2 |
| 5 | Limited contribution of NR5A1 (SF-1)mutations in women with primary ovarian insufficiency (POI) 显示文摘 | Femi J Larissa M Karen J | 2012 | Fertility and Sterility2012，97，1： | 1 |
| 6 | Decol- orization of synthetic dyes by solid state cultures of Lentinula (Lentinus) edodes producing manganese peroxidase as the main ligninolytic enzyme显示文摘 | CINTHIA G B LARISSA O CRISTINA G M S | 2004 | Bioresouree Technology2004，94，2： | 1 |
| 7 | Lobar holoprosencephaly:prenatal MR diagnosis withpostnatal MR correlation显示文摘 | Alex M Wong C Larissa T Bilaniuk K.-K.Ng | | 0，，04： | 1 |
| 8 | Oxidation of sulfur compounds in diesel fuel using Fe-TAML catalysts and hydrogen peroxide显示文摘 | Sujit M Yelda H Larissa A | 2006 | Catalysis Today2006，116，： | 1 |
| 9 | Rice ascorbate peroxidase gene family encodes functionally diverse isoforms localized in different subcellular compartments显示文摘 | Felipe Karam Teixeira Larissa Menezes-Benavente Vinícius Costa Galv?o Rogério Margis Márcia Margis-Pinheiro | 2006 | Planta2006，，2： | 1 |
| 10 | Beyond traditional surveillance:applying syndromic surveillance to developing settings-opportunities and challenges显示文摘 | Larissa M Jean C Julie P | | 0，，1： | 1 |
| 11 | Reverse knowledge trans- fer in MNES: subsidiary innovativeness and entry modes显示文摘 | RAM M LUCIA P LARISSA R | 2014 | Long Range Planning2014，47，1： | 1 |
| 12 | Analysis of the Molecular Evolutionary History of the Ascorbate Peroxidase Gene Family: Inferences from the Rice Genome显示文摘 | Felipe Karam Teixeira Larissa Menezes-Benavente Rogério Margis Márcia Margis-Pinheiro | 2004 | Journal of Molecular Evolution2004，，6： | 1 |
| 13 | Sarcol endoplasmic reticulum Ca2+ -ATPase gene transfer reduces vascular smooth muscle cell proliferation and neointima formation in the rat显示文摘 | Federicadel M Thierry C | 2005 | Circ Res2005，97，： | 1 |
| 14 | Video modeling and word identification in adolescents with Autism Spectrum Disorder 显示文摘 | LARISSA M JENNIFER L R SYCARAH F | 2015 | Child Lang Teach Ther2015，31，1： | 1 |
| 15 | YY1 binding to a subset of p53 DNA-target sites regulates p53-dependent transcription显示文摘 | Tatiana Yakovleva Larissa Kolesnikova Vladana Vukojevi? Irina Gileva Koichi Tan-No Matthias Austen Bernhard Lüscher Tomas J Ekstr?m Lars Terenius Georgy Bakalkin | 2004 | Biochemical and Biophysical Research Communications2004，，2： | 1 |
| 16 | Syntheses and structure-activity relationships of novel 3'-difluoromethyl and 3'-trifluoromethyl-taxoids显示文摘 | LARISSA V K ANTONELLA P IOANA M U | 2008 | Journal of Fluorine Chemistry2008，129，9： | 1 |
| 17 | Synthesis ofa thinl- 13-cyclodextrin, a polential ag,ent for con/rolling enzymatic browning in fruits and vegetables 显示文摘 | Carmen M Gabriela P A Larissa G | 2013 | Journal of Agricuhural and Food Chemistu2013，61，11： | 1 |
| 18 | Oxidation of sulfur compounds in diesel fuel using Fe TAML catalysts and hydrogen peroxide显示文摘 | Sujit M Yelda H Larissa A | 2006 | Catalysis Today2006，11，6： | 1 |
| 19 | Limited contribution of NRSA1 (SF-1)mutations in women with primary ovarian insufficiency ( POI ) 显示文摘 | Femi J Larissa M Karen J etal | 2012 | Fertility and Sterility2012，97，1： | 1 |
| 20 | Limited contribution of NR5A1(SF-1)mutations in women with primary ovarian insufficiency(POI)显示文摘 | Femi J Larissa M etal | 2012 | Fertility and Sterility2012，97，1： | 1 |
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