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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 | Comprehensive and innovative techniques for livertransplantation in rats: A surgical guide显示文摘AIM: To investigate our learning curves of orthotopic liver transplantation (OLT) in rats and the most important factor for successful surgery. METHODS: We describe the surgical procedures for our rat OLT model, and determined the operator learning curves. The various factors that contributed to successful surgery were determined. The most important surgical factors were evaluated between successful and unsuccessful surgeries.RESULTS: Learning curve data indicated that 50 cases were required for operator training to start a study. Operative time, blood loss, warm ischemic time, anhepatic phase, unstable systemic hemodynamic state, and body temperature after surgery significantly affected surgery success by univariate analysis, while the anhepatic phase was the most critical factor for success by multivariate analysis. CONCLUSION: OLT in rats is the only liver transplantation model that provides clinically relevant and reliable results. Shortened anhepatic phase is key to success in this model. | Tomohide Hori Justin H Nguyen Yasuhiro Ogura Toshiyuki Hata Shintaro Yagi Ann-Marie T Baine Norifumi Ohashi Christopher B Eckman Aimee R Herdt Hiroto Egawa Yasutsugu Takada Fumitaka Oike Seisuke Saka-moto Mureo Kasahara Kohei Ogawa Koichiro Hata Taku Iida Yukihide Yonekawa Lena Sibulesky Kagemasa Kuribayashi Takuma Kato Kanako Saito Mie Torii Naruhiko Sahara Naoko Kamo Tomoko Sahara Motohiko Yasutomi Shinji Uemoto | 2010 | World Journal of Gastroenterology2010，16，25： | 14 |
| 3 | 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 |
| 4 | 基于FRN技术的我国不同地区典型土壤保持措施的有效性评价显示文摘选择中国西南-东北样带4个典型土壤侵蚀区,包括位于长江上游的西昌,黄土高原延安,北方风蚀区的丰宁和东北黑土区的拜泉,应用环境放射性核素(FRN)技术研究了不同土壤保持措施在减少土壤侵蚀、改善土壤质量方面的作用。在西昌,137Cs和210Pbex的测定结果表明,不同植被覆盖结构减少土壤侵蚀的作用为:灌木>有地被物的乔木>草类>无地被物的乔木;在延安,利用137Cs示踪技术对坡地景观的产沙量估算结果表明,梯田和林草地相对于坡耕地产沙量分别减少了49%和80%,林草地的土壤有机质、碱解氮和速效磷含量相对于坡耕地分别增加了255%、198%和18%,梯田土壤有机质、碱解氮和速效磷含量分别增加了121%、103%和162%,而土壤容重分别降低了1.6%和6.4%;在丰宁,对7Be的测定结果表明,与传统耕作方式相比,4年免耕+作物高留茬(50~56cm)和免耕+作物低留茬(25cm)分别使土壤侵蚀速率下降44%和33%;在拜泉,通过137Cs测定结果发现,坡改梯使土壤流侵蚀降低14%,等高耕作使土壤侵蚀量减少了34%。研究结果说明,灌木林覆盖、林草复合结构是控制西南侵蚀山地土壤侵蚀的优选生物配置措施,梯田和林草复合结构在控制黄土高原土壤侵蚀和改善土壤质量方面有重要作用,免耕+高留茬措施是我国北方风蚀区防治土壤侵蚀退化的有效措施,等高耕作应当成为防治东北黑土区土壤侵蚀的关键措施。 | 于寒青 李勇 Nguyen M L Funk R 刘国强 李俊杰 无 | 2012 | 核农学报2012，26，2： | 6 |
| 5 | Hepatocellular carcinoma in patients with non-alcoholic fatty liver disease显示文摘Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in the United States and represents an increasingly important etiology of hepatocellular carcinoma(HCC) with annual cumulative incidence rates ranging from 2% to 12% in cohorts of NAFLD cirrhosis. While the risk of progression of NAFLD to HCC remains higher among patients with fibrosis or cirrhosis, an increasing amount of literature describes NAFLD-HCC as a disease that can occur in the absence of cirrhosis. Efforts to characterize the pathogenesis of NAFLD-HCC have suggested mechanisms that strongly associate with states of hyperinsulinemia and chronic inflammation, cellular mechanisms including adaptive immune responses and hepatic progenitor cell populations, and genetic polymorphisms including mutations of PNPLA3. Current literature describes NAFLD-HCC mostly as a disease of late presentation with lower rates of receipt of curative therapy and worse prognosis. However, a growing body of evidence has reported comparable and potentially more favorable disease-free and overall survival rates among patients with NAFLD-HCC after receipt of curative treatment. This review summarizes current evidence of epidemiology, pathophysiology, disease presentation, demand and receipt of curative therapy, post-treatment outcomes, and overall survival of NAFLD-associated HCC. | Carrie R Wong Mindie H Nguyen Joseph K Lim | 2016 | World Journal of Gastroenterology2016，22，37： | 5 |
| 6 | Comparison of inhaled milrinone, nitric oxide and prostacyclin in acute respiratory distress syndrome显示文摘AIM To evaluate the safety and efficacy of inhaled milrinone in acute respiratory distress syndrome(ARDS).METHODS Open-label prospective cross-over pilot study where fifteen adult patients with hypoxemic failure meeting standard ARDS criteria and monitored with a pulmonary artery catheter were recruited in an academic 24-bed medico-surgical intensive care unit. Random sequential administration of i NO(20 ppm) or nebulized epoprostenol(10 μg/mL) was done in all patients. Thereafter, inhaled milrinone(1 mg/mL) alone followed by inhaled milrinone in association with inhaled nitric oxide(iN O) was administered. A jet nebulization device synchronized with the mechanical ventilation was use to administrate the epoprostenol and the milrinone. Hemodynamic measurements and partial pressure of arterial oxygen(PaO_2) were recorded before and after each inhaled therapyadministration.RESULTS The majority of ARDS were of pulmonary cause(n = 13) and pneumonia(n = 7) was the leading underlying initial disease. Other pulmonary causes of ARDS were: Post cardiopulmonary bypass(n = 2), smoke inhalation injury(n = 1), thoracic trauma and pulmonary contusions(n = 2) and aspiration(n = 1). Two patients had an extra pulmonary cause of ARDS: A polytrauma patient and an intra-abdominal abscess Inhaled nitric oxide, epoprostenol, inhaled milrinone and the combination of inhaled milrinone and i NO had no impact on systemic hemodynamics. No significant adverse events related to study medications were observed. The median increase of PaO 2 from baseline was 8.8 mmH g [interquartile range(IQR) = 16.3], 6.0 mm Hg(IQR = 18.4), 6 mm Hg(IQR = 15.8) and 9.2 mm Hg(IQR = 20.2) respectively with i NO, epoprostenol, inhaled milrinone, and i NO added to milrinone. Only i NO and the combination of inhaled milrinone and i NO had a statistically significant effect on PaO 2. CONCLUSION When comparing the effects of inhaled NO, milrinone and epoprostenol, only NO significantly improved oxygenation. Inhaled milrinone appeared safe but failed to improve oxygenation in ARDS. | Martin Albert Daniel Corsilli David R Williamson Marc Brosseau Patrick Bellemare Stéphane Delisle Anne QN Nguyen France Varin | 2017 | World Journal of Critical Care Medicine2017，6，1： | 4 |
| 7 | Novel diet-related mouse model of colon cancer parallels human colon cancer显示文摘AIM:To investigate the close parallels between our novel diet-related mouse model of colon cancer and human colon cancer.METHODS:Twenty-two wild-type female mice(ages 6-8 wk)were fed the standard control diet(AIN-93G)and an additional 22 female mice(ages 6-8 wk)were fed the control diet supplemented with 0.2%deoxycho-lic acid[diet+deoxycholic acid(DOC)]for 10 mo.Tu-mors occurred in the colons of mice fed diet+DOC and showed progression to colon cancer[adenocarcinoma(AC)].This progression is through the stages of tubular adenoma(TA),TA with high grade dysplasia or ad-enoma with sessile serrated morphology,intramucosal AC,AC stage T1,and AC stage T2.The mouse tumors were compared to human tumors at the same stages by histopathological analysis.Sections of the small and large intestines of mice and humans were evaluated for glandular architecture,cellular and nuclear morphology including cellular orientation,cellular and nuclear atyp-ia,pleomorphism,mitotic activity,frequency of goblet cells,crypt architecture,ulceration,penetration of crypts through the muscularis mucosa and presence of malignant crypts in the muscularis propria.In addition,preserved colonic tissues from genetically similar male mice,obtained from a prior experiment,were analyzed by immunohistochemistry.The male mice had been fed the control diet or diet+DOC.Four molecular markers were evaluated:8-OH-dG,DNA repair protein ERCC1,autophagy protein beclin-1 and the nuclear location of beta-catenin in the stem cell region of crypts.Also,male mice fed diet+DOC plus 0.007%chlorogenic acid(diet+DOC+CGA)were evaluated for ERCC1,beclin-1 and nuclear location of beta-catenin.RESULTS:Humans with high levels of diet-relatedDOC in their colons are at a substantially increased riskof developing colon cancer.The mice fed diet+DOChad levels of DOC in their colons comparable to that ofhumans on a high fat diet.The 22 mice without addedDOC in their diet had no colonic tumors while 20 ofthe 22 mice(91%)fed diet+DOC developed colonictumors.Furthermore,the tumors in 10 of these mice(45%of mice)included an adenocarcinoma.All micewere free of cancers of the small intestine.Histopatho-logically,the colonic tumor types in the mice werevirtually identical to those in humans.In humans,char-acteristic aberrant changes in molecular markers can be detected both in field defects surrounding cancers(from which cancers arise)and within cancers.In thecolonic tissues of mice fed diet+DOC similar changesin biomarkers appeared to occur.Thus,8-OH-dG wasincreased,DNA repair protein ERCC1 was decreased,autophagy protein beclin-1 was increased and,in thestem cell region at the base of crypts there was sub-stantial nuclear localization of beta-catenin as well asincreased cytoplasmic beta-catenin.However,in micefed diet+DOC+CGA(with reduced frequency ofcancer)and evaluated for ERCC1,beclin-1,and beta-catenin in the stem cell region of crypts,mouse tissueshowed amelioration of the aberrancies,suggestingthat chlorogenic acid is protective at the molecular levelagainst colon cancer.This is the first diet-related modelof colon cancer that closely parallels human progressionto colon cancer,both at the histomorphological level aswell as in its molecular profile.CONCLUSION:The diet-related mouse model of coloncancer parallels progression to colon cancer in humans,and should be uniquely useful in model studies of pre-vention and therapeutics. | Anil R Prasad Shilpa Prasad Huy Nguyen Alexaner Facista Cristy Lewis Beryl Zaitlin Harris Bernstein Carol Bernstein | 2014 | World Journal of Gastrointestinal Oncology2014，6，7： | 2 |
| 8 | Presence of phthalates in gastrointestinal medications: Is there a hidden danger?显示文摘Pharmaceutical companies that produce gastrointestinal(GI)medications often utilize phthalates for their ability to localize medication release.Commonly prescribed GI medications that may utilize phthalates are 5-Aminosalicylates,proton pump inhibitors,and pancreatic enzymes.Our understanding of the cumulative health effects of phthalates from medications remains unclear,and there is increasing evidence that phthalates are not harmless.Experimental studies in animals have shown that phthalates,specifically dibutyl phthalate and Di-(2-ethyl-hexyl)phthalate,have the potential to alter and/or inhibit reproductive biology and in utero development.Despite the lack of definitive human data,many cohort and cross-sectional studies demonstrate concerning associations between phthalates and poor health status,specifically developmental problems.Longitudinal studies and studies with larger sample sizes are required to determine whether phthalates actually cause negative health consequences.It is also important that physicians regularly review and discuss with patients the medicinal ingredients in their medications and supplements,specifically in pregnant woman with inflammatory bowel disease. | Zane R Gallinger Geoffrey C Nguyen | 2013 | World Journal of Gastroenterology2013，19，41： | 2 |
| 9 | Some result in the theory of crosstalk - free transmultiplexers 显示文摘 | KOILPILLAI R D NGUYEN T Q VAIDYANATHAN P P | 1991 | IEEE Trans on Signal Processing1991，39，1： | 2 |
| 10 | Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury显示文摘 | Caudrillier Axelle Kessenbrock Kai Gilliss Brian M Nguyen John X Marques Marisa B Monestier Marc Toy Pearl Werb Zena Looney Mark R | 2012 | EN2012，，7： | 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 | A water and heat management model for proton-exchange- membrane fuel cells 显示文摘 | NGUYEN T V WHITE R E | 1993 | Journal Electrochem Soc1993，140，8： | 1 |
| 13 | Diffusion Coefficients of Uranium (Ⅵ), Rhenium (Ⅶ) and Technetium (Ⅶ) in Nitric Acid and Tri-Bu-tylphosphate Diluted in Dodecane显示文摘 | Nabeshima M Ludwig R Nguyen T K D | 2000 | Solvent Extr Res Dev2000，7，： | 1 |
| 14 | The impact of delaying en- teral feeding on gastric emptying, plasma cholecystokinin, and pep- tide YY concentrations in critically ill patients显示文摘 | Nguyen NQ Fraser R J Bryant LK | 2008 | Crit Care Med2008，36，5： | 1 |
| 15 | Integrat- ed probabilistic framework for domino effect and risk analysis 显示文摘 | Nguyen Q B Mebarki A Saada R A | 2009 | Advances in Engineering Software2009，，40： | 1 |
| 16 | Do additional echocardiographic variables increase the accuracy of E/E' for predicting left ventricular filling pressure in normal ejection fraction? An echocardiographic and invasive hemo- dynamic study 显示文摘 | Dokainish H Nguyen JS Sengupta R | 2010 | J Am Soc Echocardiogr2010，23，： | 1 |
| 17 | Isothermal start-up of pipeline transporting waxy crude oil显示文摘 | Cheng Chang Nguyen Q Dzuy Hans Petter R?nningsen | 1999 | J Non-Newtonian Fluid Mech1999，87，： | 1 |
| 18 | Laterally driven poly-silicon resonant microstructures 显示文摘 | Tang W C Nguyen Tu-Cuong H Howe R T | 1989 | Sensors and Actuators1989，20，12： | 1 |
| 19 | Treatment of hand is- chemia with arterialization of the venous of the hand: report of three cases 显示文摘 | Nguyen PSA Legre R Gay AM | 2011 | Annales de Chirurgie Plastique et Esthetique2011，56，3： | 1 |
| 20 | Inhibition ofCD4+ CD25+ regulatory T-cell function by calcineurindependentinterleukin-2 production 显示文摘 | ZEISER R NGUYEN Y H BEILHACK A | 2006 | Blood2006，108，1： | 1 |
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