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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 | Differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mTORC1-dependent pathway显示文摘Neonatal growth is characterized by a high protein synthesis rate that is largely due to an enhanced sensitivity to the postprandial rise in insulin and amino acids, especially leucine. The mechanism of leucine's action in vivo is not well understood. In this study, we investigated the effect of leucine infusion on protein synthesis in skeletal muscle and liver of neonatal pigs. To evaluate the mode of action of leucine, we used rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) complex-1 (mTORC1). Overnight-fasted 7-day-old piglets were treated with rapamycin for 1 hour and then infused with leucine (400 μmol·kg -1 ·h -1 ) for 1 hour. Leucine infusion increased the rate of protein synthesis, and ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E-BP1) phosphorylation in gastrocnemius and masseter muscles (P < 0.05), but not in the liver. The leucine-induced stimulation of protein synthesis and S6K1 and 4E-BP1 phosphorylation were completely blocked by rapamycin, suggesting that leucine action is by an mTORC1-dependent mechanism. Neither leucine nor rapamycin had any effect on the activation of the upstream mTORC1 regulators, AMP-activated protein kinase and protein kinase B, in skeletal muscle or liver. The activation of eIF2a and elongation factor 2 was not affected by leucine or rapamycin, indicating that these two pathways are not limiting steps of leucine-induced protein synthesis. These results suggest that leucine stimulates muscle protein synthesis in neonatal pigs by inducing the activation of mTORC1 and its downstream pathway leading to mRNA translation. | Agus Suryawan Hanh V Nguyen Rosemarie D Almonaci Teresa A Davis | 2012 | Journal of Animal Science and Biotechnology2012，3，1： | 9 |
| 3 | Vascular endothelial growth factor trap-eye(Aflibercept) for the management of diabetic macular edema显示文摘Diabetic retinopathy(DR)is the most common cause of visual loss among working age individuals.Diabetic macular edema(DME)is an important complication of DR that affects around one third of the patients with DR.Several treatments have been approved for DME ranging from blood pressure and glycemic control to photocoagulation and more recently the use of vascular endothelial growth factor(VEGF)antagonists.The index review discusses aflibercept(EYLEA-Regeneron Pharmaceuticals,Inc.,Tarrytown,New York,NY,and Bayer Healthcare Pharmaceuticals,Berlin,Germany)in the context of other VEGF antagonists currently available for the treatment of DME.A systematic search of literature was conducted on PubMed,Scopus,and Google Scholar with no limitation on language or year of publication.Pre-clinical studies of aflibercept have shown a higher affinity of this molecule for vascular endothelial growth factor A(VEGF-A)along with a longer duration of action as compared to other VEGF antagonists.Recent clinical trials have shown visual outcome results for aflibercept to be similarly favorable as compared to other available agents with the added benefit of fewer required injections and less frequent monitoring.Aflibercept presents a potential exciting new addition to the armamentarium of current VEGF antagonists available for the treatment of DME and other retinal vascular diseases.However,further studies are indicated to confirm the role,safety,and efficacy of aflibercept for DME. | Ahmadreza Moradi Yasir Jamal Sepah Mohammad Ali Sadiq Humzah Nasir Salima Kherani Raafay Sophie Diana V Do Quan Dong Nguyen | 2013 | World Journal of Diabetes2013，4，6： | 8 |
| 4 | Efficacy and safety of tenofovir in chronic hepatitis B: Australian real world experience显示文摘AIM To evaluate the long-term treatment outcomes of tenofovir therapy in patients in a real world Australian tertiary care setting.METHODS We performed a retrospective analysis of treatment outcomes among treatment-na?ve and treatment-experienced patients receiving a minimum 3 mo tenofovir therapy through St Vincent's Hospital Melbourne, Australia. We included patients receiving tenofovir [tenofovir disoproxil fumarate(TDF)] monotherapy, as well as patients treated with TDF in combination with a second antiviral agent. Patients were excluded if they demonstrated human immune-deficiency virus/hepatitis C virus/hepatitis delta virus coinfection or were less than 18 years of age. We considered virological and biochemicalresponse, as well as safety outcomes. Virological response was determined by measurement of hepatitis B virus(HBV) DNA using sensitive assays; biochemical response was determined via serum liver function tests; histological response was determined from liver biopsy and fibroscan; safety analysis focused on glomerular renal function and bone mineral density. The primary efficacy endpoint was complete virological suppression over time, defined by HBV DNA < 20 IU/m L. Secondary efficacy endpoints included rates of biochemical response, and HB e antigen(HBe Ag)/HB surface antigen loss and seroconversion over time.RESULTS Ninety-two patients were identified who fulfilled the enrolment criteria. Median follow-up was 26 mo(range 3-114). Mean age was 46(24-78) years, 64(70%) were male and 77(84%) were of Asian origin. 55(60%) patients were treatment-na?ve and 62 patients(67%) were HBe Ag-negative. Complete virological suppression was achieved by 45/65(71%) patients at 12 mo, 37/46(80%) at 24 mo and 25/28(89%) at 36 mo. Partial virological response(HBV DNA 20-2000 IU/m L) was achieved by 89/92(96.7%) of patients. Multivariate analysis showed a significant relationship between virological suppression at end of follow-up and baseline HBV DNA level(OR = 0.897, 95%CI: 0.833-0.967, P = 0.0046) and HBe Ag positive status(OR = 0.373, 95%CI: 0.183-0.762, P = 0.0069). There was no difference in response comparing treatment-na?ve and treatment-experienced patients. Three episodes of virological breakthrough occurred in the setting of noncompliance. Tenofovir therapy was well tolerated.CONCLUSION Tenofovir is an efficacious, safe and well-tolerated treatment in an Australian real-world tertiary care setting. Our data are similar to the reported experience from registration trials. | Grace C Lovett Tin Nguyen David M Iser Jacinta A Holmes Robert Chen Barbara Demediuk Gideon Shaw Sally J Bell Paul V Desmond Alexander J Thompson | 2017 | World Journal of Hepatology2017，9，1： | 7 |
| 5 | 基于AFM的纳米尺度线宽计量模型及其算法的研究显示文摘纳米尺度线宽的测量广泛应用于半导体制造、数据存储、微机电系统等领域。随着制造技术的进步,线宽的极限尺寸也变得越来越小,目前已经缩小至100 nm左右。在这一尺度范围内,由于样本制造技术的限制和测量仪器的影响,目前很难得到准确的测量结果。为了获得样本的真实几何尺寸信息,剔除测量方法和仪器本身对测量结果的影响,建立了一个基于AFM测量技术的线宽计量模型和相应算法。该模型将被测样本的截面轮廓用20个关键点分成5个部分共19段,用基于最小二乘的直线来拟合实际轮廓。应用该模型和算法可以分别得到单刻线轮廓拟合前后的顶部线宽b_T、b_(TF),中部线宽b_M、b_(MF),底部线宽b_B、b_(BF),左右边墙角A_L、A_R,以及高度h_。使用NanoScope Ⅲa型AFM对一个单晶硅(Si)线宽样本进行了测量,测量结果表明该模型和算法可以满足纳米尺度线宽计量的基本要求。 | 赵学增 褚巍 Theodore V Vorburger Joseph Fu John Song Cattien V Nguyen | 2004 | 机械工程学报2004，40，4： | 7 |
| 6 | Innate and adaptive immune responses in male and female reproductive tracts in homeostasis and following HIV infection显示文摘男、女的繁殖的道是有多样的功能的要求的复杂微型环境。当同时对潜在的病原体授与保护时,在繁殖的道的免疫系统举办为胎儿的 allograft 提供保护的环境的费力的任务。因此,它发展了改编的一个唯一的集合,首先在性荷尔蒙的影响下面,它从另外的 mucosal 地点使它不同。这里,我们讨论在男性和女繁殖的道是在场的免疫系统的各种各样的部件,包括在 homeostatic 条件下面的天生的可溶的因素和房间和体液、调停房间的适应免疫。我们考察在从全身的豁免展出区分并且讨论这些特征怎么被性荷尔蒙影响的男、女的繁殖的道显示出唯一的 phenotypic 和有免疫力的房间和回答的功能的特征的证据。我们也在跟随 HIV-1 感染的繁殖的道,性荷尔蒙和有免疫力的回答之中检验相互作用。男、女的繁殖的道的唯一的特征的改进理解将提供卓见进为性播送的感染的预防改进不孕的免疫学的原因和预防干预的设计的临床的处理。 | Philip V Nguyen Jessica K Kafka Victor H Ferreira Kristy Roth Charu Kaushic | 2014 | Cellular & Molecular Immunology2014，11，5： | 7 |
| 7 | STAT3 and sphingosine-1-phosphate in inflammation-associated colorectal cancer显示文摘Accumulated evidences have demonstrated that signal transducer and activator of transcription 3(STAT3)is a critical link between inflammation and cancer.Multiple studies have indicated that persistent activation of STAT3 in epithelial/tumor cells in inflammation-associated colorectal cancer(CRC)is associated with sphingosine-1-phosphate(S1P)receptor signaling.In inflammatory response whereby interleukin(IL)-6 production is abundant,STAT3-mediated pathways were found to promote the activation of sphingosine kinases(SphK1and SphK2)leading to the production of S1P.Reciprocally,S1P encourages the activation of STAT3 through a positive autocrine-loop signaling.The crosstalk between IL-6,STAT3 and sphingolipid regulated pathways may play an essential role in tumorigenesis and tumor progression in inflamed intestines.Therapeutics targeting both STAT3 and sphingolipid are therefore likely to contribute novel and more effective therapeutic strategies against inflammation-associated CRC. | Andrew V Nguyen Yuan-Yuan Wu Elaine Y Lin | 2014 | World Journal of Gastroenterology2014，20，30： | 7 |
| 8 | Cancer and age related colonic crypt deficiencies in cytochrome c oxidase Ⅰ显示文摘AIM: To investigate whether defi ciency of expressionof cytochrome c oxidase I (CcOI) in colonic crypts is associated with colon cancer.METHODS: The pattern and level of expression of CcOI in non-neoplastic colonic crypts,and in dysplastic tissues,was assessed using standard immunohis-tochemical methods.Biopsies were obtained from individuals undergoing colonoscopies for screening purposes or for a medically indicated reason.Tissue samples were also obtained from surgical colonic resections.Samples from resections were taken from colonic mucosa 1 and 10 cm from tumors and from the tumors themselves.Samples were evaluated for frequency of crypts with reduced or absent expression of CcOI.In most crypts the loss was apparent throughout the entire crypt,while in a small minority the loss was segmental.The strong immunoreactivity using this monoclonal antibody makes the scoring unambiguous.The percent of crypts with reduced or absent expression of CcOI or (infrequent) segmented loss of expression was then calculated.Data analyses were performed using SPSS statistical package 17.0.RESULTS: The average frequency of CcOI deficient crypts (CcOI-DC) is low in individuals between 20 and 39 years of age,with 0.48% ± 0.40% CcOI-DC for women and 1.80% ± 0.35% for men.CcOI-DC increases after age 40 years,so that between the ages of 40 and 44 years the average frequency of CcOI- DC goes up to 5.89% ± 0.84% in women and 2.15% ± 1.27% in men.By 80-84 years of age,the average frequency of CcOI-DC goes up in women to 15.77% ± 0.97% and in men to 22.6% ± 0.65%.The increases in CcOI-DC from ages 40-44 years compared to 80-84 years in women and men are significantly different with P < 0.01.For women over age 60 years,deficiency of CcOI expression is greater in those women who have had a cancer in their colon.The frequency of CcOI-DC,measured in men,increased in tissues adjacent to colon cancer,being 4.03% ± 0.27% in individuals free of neoplasia in the age range 55-64 yearsand 14.13% ± 0.35% in resected histologically normal tissue of men with cancer in the same age range,P < 0.001.Similar signifi cant differences were noted in older age ranges.The frequency of CcOI-DC crypts in the cecum and sigmoid colon of an individual are signifi cantly correlated,with an R2 = 0.414 for women and R2 = 0.528 for men,P < 0.001.This suggests that the factors determining the level of CcOI deficiency act throughout the colon.Most defective crypts are in clusters of two or more,a likely consequence of crypt fission.In the non-neoplastic margins of cancers,crypts are frequently defi cient for CcOI,and such crypts may appear in large clusters,some containing more than 100 defi cient crypts.CcOI defi ciency is also apparent in colon cancers and sometimes involves a large section of the tumor.Overall,CcOI deficient cells can be visualized in segments of crypts,in whole crypts that increase in frequency with age,in crypts undergoing f ission,in clusters of crypts where the clusters increase in size with age,in increased frequency near tumors,in large clusters in the intimate margins of tumors,and in the tumors themselves.There is no clear dividing line between early stages that can be considered aspects of aging and later stages that can be considered aspects of the progression to cancer.This ambiguity may re ect a rather general situation leading to adult cancer where the early stages of cellular change appear to be relatively innocuous features of the aging process but over decades may evolve into malignancy.CONCLUSION: CcOI defi cient crypts increase in frequency with age,and clusters of defi cient crypts are associated with,and may give rise to,colon cancer. | Carol Bernstein Alexander Facista Huy Nguyen Beryl Zaitlin Nadia Hassounah Cristy Loustaunau Claire Margaret Payne Bhaskar Banerjee Steve Goldschmid V Liana Tsikitis Robert Krouse Harris Bernstein | 2010 | World Journal of Gastrointestinal Oncology2010，2，12： | 5 |
| 9 | Interventions and targets aimed at improving quality in inflammatory bowel disease ambulatory care显示文摘Over the past decade,there has been increasing focus on improving the quality of healthcare delivered to patients with chronic diseases,including inflammatory bowel disease.Inflammatory bowel disease is a complex,chronic condition with associated morbidity,health care costs,and reductions in quality of life.The condition is managed primarily in the outpatient setting.The delivery of high quality of care is suboptimal in several ambulatory inflammatory bowel disease domains including objective assessments of disease activity,the use of steroid-sparing agents,screening prior to anti-tumor necrosis factor therapy,and monitoring thiopurine therapy.This review outlines these gaps in performance and provides potential initiatives aimed at improvement including reimbursement programs,quality improvement frameworks,collaborative efforts in quality improvement,and the use of healthcare information technology. | Adam V Weizman Geoffrey C Nguyen | 2013 | World Journal of Gastroenterology2013，19，38： | 4 |
| 10 | Magnetic field effects on the binding energy of hydrogen impurities in quantum dot with parabolic confinements 显示文摘 | NGUYEN V L VGUYEN M T NGUYEN T D | 2000 | Physica B2000，292，： | 2 |
| 11 | IL 28 B genotype is not useful for predicting treatment outcome in A sian chronic hepatitis B patients treated with pegylated interferon‐α显示文摘 | Jacinta A Holmes Tin Nguyen Dilip Ratnam Neel M Heerasing Jane V Tehan Sara Bonanzinga Anouk Dev Sally Bell Stephen Pianko Robert Chen Kumar Visvanathan Rachel Hammond David Iser Ferry Rusli William Sievert Paul V Desmond D Scott Bowden Alexander J Thomps | 2013 | J Gastroenterol Hepatol2013，，5： | 2 |
| 12 | Skin fold thickness at abdomen:a simple anthropometric measurement may compliment metabolic syndrome definition in patients with normal waist circumference显示文摘Backgroud and Objectives Previous studies have reported that skin fold thickness (SF) strongly correlated with insulin resistance in the metabolic syndrome (MetS). In this study, we developed a MetS definition by SF at A8 point (SFA8) on Erdheim diagram(MetSSFA8) in essential hypertensive patients. Subjects and Methods Medical records of 268 essential hypertensive patients (126males and 122 females) were analyzed, including 210 non-diabetic patients (NDM group) and 58 patients with diabetes (DM group).The mean age was 61.4 ± 9.9 and 59.0 ± 11.0 years, respectively. The control group consisted of 90 non-diabetic, non-hypertensive patients with a mean age of 58.0 ± 11.3 years. The proposed MetSSFA8 definition included SFA8 specific values ( ≥30 mm in female and ≥27 mm in male) and at least two of the following: raised triglyceride levels ( ≥1.7 mmol/L), or specific treatment for this lipid abnormality; raised blood pressure (SBP≥130 mmHg and/or DBP≥85 mmHg), or treatment of previously diagnosed hypertension;reduced HDL-cholesterol (< 1.03 mmol/L in men, <1.29 mmol/L in women), or specific treatment for this lipid abnormality; raised fasting plasma glucose (≥5.6 mmol/l), or previously diagnosed DM. Metabolic Syndrome by the National Cholesterol Education Program and International Diabetes Federation definitions were determined with abdominal obesity defined by Asia-Pacific criteria for waist circumference (NCEPA and IDFA). Results The percentage of MetS as defined by NCEPA, IDFA and MetSSFA8 in NDM group was lower than that of NCEPA, IDFA and MetSSFA8 in DM group [OR=7.7 (95%CI, 2.9-20.2) and 2.5 (95%CI, 1.4-4.8) and 2.7(95%CI, 1.3-5.6), respectively] and higher than that of the control group [OR=53.3 (95%CI, 16.7-170.6), 5.8 (95%CI, 2.6-13.2) and18.8 (95%CI, 7.3-48.7), respectively]. The percentage of MetS by NCEPA, IDFA and MetSSFA8 in males in NDM group was lower than the percentage of MetS by NCEPA, IDFA and MetSSFA8 in females in NDM group (50.8% and 77.9%, P< 0.001; 15,9% and 67.2%, P< 0.001; 60.3% and 73.8%, P <0.05, respectively). In subjects with normal WC or both normal WC and BMI, the percentage of MetS by SFAS was higher than that the percentage of MetS by NCEPA (36.9% and 50.8%, P< 0.05 and 36.0% and 51.0%, P< 0.05).The sensitivity, specificity, false positive rate, positive predictive value, negative predictive value of MetSSFA8 assessed with NCEPA definitions were 0.87, 0.73, 0.27, 0.79 and 0.82, respectively. There was a close agreement between MetSSFA8 and NCEPA (The coefficient of Kapa was 0.60, P< 0.001). Conclusions The MetSSFA8 definition was developed which may be useful in order to define and manage MetS in patients with normal WC or normal weight. | Toan C Nguyen Thai Q Ngo Son V Nguyen Hieu T Luong Khoa TA Pham Cong D Nguyen | 2006 | Journal of Geriatric Cardiology2006，3，2： | 2 |
| 13 | 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 |
| 14 | Effects of high-temperature annealing on the dielectric function of Ta2O5 films observed by spectroscopic eUipsometry 显示文摘 | Nguyen N V Richter C A Cho Y J | 2000 | Applied Physics Letters2000，77，： | 1 |
| 15 | Liquid drainage in single plateau borders of foam显示文摘 | Nguyen A V | 2002 | Journal of Colloid and Interface Science2002，249，1： | 1 |
| 16 | Quorum sensing controls expression of the type Ⅲ secretion gene transcription and protein secretion in enterohemorrhagic and enteropathogenic Escherichia coli显示文摘 | Sperandio V Mellies JL Nguyen W | 1999 | Proc Natl Acad Sci USA1999，96，15： | 1 |
| 17 | Synthetic mammalian prions显示文摘 | Legname G Baskakov I V Nguyen H O | 2004 | Science2004，305，5684： | 1 |
| 18 | Computational fluid dynamics modeling of gas jets impinging onto liquid pools 显示文摘 | Anh V Nguyen Geoffrey M Evans | 2006 | Applied Mathematical Modelling2006，30，： | 1 |
| 19 | Oral N-carbamylglu- tamate supplementation inereases protein synthesis in skeletal muscle of piglets显示文摘 | Frank J W Escobar J Nguyen H V | 2007 | J Nutr2007，137，2： | 1 |
| 20 | Tunable arbitrary N-port CRLH infinite wavelength series power divider显示文摘 | Nguyen H V Caloz C | 2007 | Electronics letters2007，43，23： | 1 |
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