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1IDO1 in cancer: a Gemini of immune checkpoints显示文摘Indoleamine 2,3-dioxygenase 1(IDO1)is a rate-limiting metabolic enzyme that converts the essential amino acid tryptophan(Trp)into downstream catabolites known as kynurenines.Coincidently,numerous studies have demonstrated that IDO1 is highly expressed in multiple types of human cancer.Preclinical studies have further introduced an interesting paradox:while single-agent treatment with IDO1 enzyme inhibitor has a negligible effect on decreasing the established cancer burden,approaches combining select therapies with IDO1 blockade tend to yield a synergistic benefit against tumor growth and/or animal subject survival.Given the high expression of IDO1 among multiple cancer types along with the lack of monotherapeutic efficacy,these data suggest that there is a more complex mechanism of action than previously appreciated.Similar to the dual faces of the astrological Gemini,we highlight the multiple roles of IDO1 and review its canonical association with IDO1-dependent tryptophan metabolism,as well as documented evidence confirming the dispensability of enzyme activity for its immunosuppressive effects.The gene transcript levels for IDO1 highlight its strong association with T-cell infiltration,but the lack of a universal prognostic significance among all cancer subtypes.Finally,ongoing clinical trials are discussed with consideration of IDO1-targeting strategies that enhance the efficacy of immunotherapy for cancer patients。Lijie Zhai Erik Ladomersky Alicia Lenzen Brenda Nguyen Ricky Patel Kristen L Lauing Meijing Wu Derek A Wainwright 2018Cellular & Molecular Immunology2018,15,5:17
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
3Differential 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 2012Journal of Animal Science and Biotechnology2012,3,1:9
4Efficacy 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 2017World Journal of Hepatology2017,9,1:7
5Osteoprotegerin: 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 1997Cell1997,,2:6
6Optimizing hepatitis C virus treatment through pharmacist interventions: Identification and management of drug-drug interactions显示文摘AIM To quantify drug-drug-interactions(DDIs) encountered in patients prescribed hepatitis C virus(HCV) treatment, the interventions made, and the time spent in this process.METHODS As standard of care, a clinical pharmacist screened for DDIs in patients prescribed direct acting antiviral(DAA) HCV treatment between November 2013 and July 2015 at the University of Colorado Hepatology Clinic. HCV regimens prescribed included ledipasvir/sofosbuvir(LDV/SOF), paritaprevir/ritonavir/ombitasvir/dasabuvir(OBV/PTV/r + DSV), simeprevir/sofosbuvir (SIM/SOF), and sofosbuvir/ribavirin (SOF/RBV). This retrospective analysis reviewed the work completed by the clinical pharmacist in order to measure the aims identified for the study. The number and type of DDIs identified were summarized with descriptive statistics.RESULTS Six hundred and sixty four patients(83.4% Caucasian, 57% male, average 56.7 years old) were identified; 369 for LDV/SOF, 48 for OBV/PTV/r + DSV, 114 for SIM/SOF, and 133 for SOF/RBV. Fifty-one point five per cent of patients were cirrhotic. Overall, 5217 medications were reviewed (7.86 medications per patient) and 781 interactions identified (1.18 interactions per patient). The number of interactions were fewest for SOF/RBV (0.17 interactions per patient) and highest for OBV/PTV/r + DSV (2.48 interactions per patient). LDV/SOF and SIM/SOF had similar number of interactions (1.28 and 1.48 interactions per patient, respectively). Gastric acid modifiers and vitamin/herbal supplements commonly caused interactions with LDV/SOF. Hypertensive agents, analgesics, and psychiatric medications frequently caused interactions with OBV/PTV/r + DSV and SIM/SOF. To manage these interactions, the pharmacists most often recommended discontinuing the medication (28.9%), increasing monitoring for toxicities (24.1%), or separating administration times (18.2%). The pharmacist chart review for each patient usually took approximately 30 min, with additional time for more complex patients. CONCLUSION DDIs are common with HCV medications and management can require medication adjustments and increased monitoring. An interdisciplinary team including a clinical pharmacist can optimize patient care.Jacob A Langness Matthew Nguyen Amanda Wieland Gregory T Everson Jennifer J Kiser 2017World Journal of Gastroenterology2017,23,9:5
7法国POLA研究组评估2016WHO弥漫性胶质瘤分类的预后价值显示文摘新的WHO分类中弥漫性胶质瘤定义更为精确,包括1p/19q共缺失、IDH1/2突变和组蛋白H3-K27M突变。该文目的是法国POLA研究组对更新的WHO(2016)分类的预后价值进行评估。所有送至中心行病理检查和纳入法国全国性POLA队列研究中的高级别少突胶质细胞瘤,Tabouret E Nguyen A T Dehais C, et al. 李晓玲 王行富 2016临床与实验病理学杂志2016,32,12:3
8Bulk endocytosis at neuronal synapses显示文摘Neurotransmitter-containing synaptic vesicle(SV)fusion with the nerve terminal plasma membrane initiates neurotransmission in response to neuronal excitation.Under mild stimulation,the fused vesicular membrane is retrieved via kiss-and-run and/or clathrin-mediated endocytosis,which is sufficient to maintain recycling of SVs.When neurons are challenged with very high stimulation,the number of fused SVs can be extremely high,resulting in significant plasma membrane addition.Under such conditions,a higher capacity retrieval pathway,bulk endocytosis,is activated to redress this large membrane imbalance.Despite first being described more than 40 years ago,the molecular mechanisms underpinning this important process have yet to be clearly defined.In this review,we highlight the current evidence for bulk endocytosis and its prevalence in various neuronal models,as well as discuss the underlying molecular components.NGUYEN Tam H QIU XuFeng SUN JianYuan MEUNIER Frederic A 2014Science China(Life Sciences)2014,57,4:3
9Outcomes of Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding显示文摘AIM:To evaluate weight loss and surgical outcomes of Roux-en-Y gastric bypass(RYGB)and laparoscopic adjustable gastric band(LAGB).METHODS:Data relating to changes in body mass index(BMI)and procedural complications after RYGB(1995-2009;n=609;116M:493F;42.4±0.4 years)or LAGB(2004-2009;n=686;131M:555F;37.2±0.4years)were extracted from prospective databases.RESULTS:Pre-operative BMI was higher in RYGB than LAGB patients(46.8±7.1 kg/m2vs 40.4±4.2 kg/m2,P<001);more patients with BMI<35 kg/m2underwent LAGB than RYGB(17.1%vs 4.1%,P<0.0001).BMI decrease was greater after RYGB.There were direct relationships between weight loss and pre-operative BMI(P<0.001).Although there was no difference in weight loss between genders during the first 3-year post-surgery,male LAGB patients had greater BMI reduction than females(-8.2±4.3 kg/m2vs-3.9±1.9kg/m2,P=0.02).Peri-operative complications occurred more frequently following RYGB than LAGB(8.0%vs0.5%,P<0.001);majority related to wound infection.LAGB had more long-term complications requiring corrective procedures than RYGB(8.9%vs 2.1%,P<0.001).Conversion to RYGB resulted in greater BMI reduction(-9.5±3.8 kg/m2)compared to removal and replacement of the band(-6.0±3.0 kg/m2).Twelve months post-surgery,fasting glucose,total cholesterol and low density lipoprotein levels were significantly lower with the magnitude of reduction greater in RYGB patients.CONCLUSION:RYGB produces substantially greater weight loss than LAGB.Whilst peri-operative complications are greater after RYGB,long-term complication rate is higher following LAGB.Nam Q Nguyen Philip Game Justin Bessell Tamara L Debreceni Melissa Neo Carly M Burgstad Pennie Taylor Gary A Wittert 2013World Journal of Gastroenterology2013,19,36:3
10Gastric per-oral endoscopic myotomy: Current status and future directions显示文摘Gastroparesis, or symptomatic delayed gastric emptying in the absence of mechanical obstruction, is a challenging and increasingly identified syndrome. Medical options are limited and the only medication approved by the Food and Drug Administration for treatment of gastroparesis is metoclopramide, although other agents are frequently used off label. With this caveat, first-line treatments for gastroparesis include dietary modifications, antiemetics and promotility agents, although these therapies are limited by suboptimal efficacy and significant medication side effects. Treatment of patients that fail first-line treatments represents a significant therapeutic challenge. Recent advances in endoscopic techniques have led to the development of a promising novel endoscopic therapy for gastroparesis via endoscopic pyloromyotomy, also referred to as gastric per-oral endoscopic myotomy or per-oral endoscopic pyloromyotomy. The aim of this article is to review the technical aspects of the per-oral endoscopic myotomy procedure for the treatment of gastroparesis, provide an overview of the currently published literature, and outline potential next directions for the field.Alexander Podboy Joo Ha Hwang Linda A Nguyen Patricia Garcia Thomas A Zikos Afrin Kamal George Triadafilopoulos John O Clarke 2019World Journal of Gastroenterology2019,25,21:3
11Method of delivery and pregnancy outcomes in Asia: the WHO global survey on maternal and perinatal health 2007–08显示文摘Pisake Lumbiganon Malinee Laopaiboon A Metin Gülmezoglu Jo?o Paulo Souza Surasak Taneepanichskul Pang Ruyan Deepika Eranjanie Attygalle Naveen Shrestha Rintaro Mori Nguyen Duc Hinh Hoang Thi Bang Tung Rathavy Kang Chuyun Kannitha Cheang Mario Festin Venus 2010The Lancet2010,,9713:2
12IL 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 2013J Gastroenterol Hepatol2013,,5:2
13A toxicity testing protocol using a bioluminescent reporter bacterium from activated sludge显示文摘Lajoie C A Lin S C Nguyen H 2002Journal of Microbiological Methods2002,50,3:2
14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
15Modeling cardiac arrest and resuscitation in the domestic pig显示文摘Cardiac arrest remains a leading cause of death and permanent disability worldwide. Although many victims are initially resuscitated, they often succumb to the extensive ischemia-reperfusion injury inflicted on the internal organs, especially the brain. Cardiac arrest initiates a complex cellular injury cascade encompassing reactive oxygen and nitrogen species, Ca2+ overload, ATP depletion, pro- and anti-apoptotic proteins, mitochondrial dysfunction, and neuronal glutamate excitotoxity, which injures and kills cells, compromises function of internal organs and ignites a destructive systemic inflammatory response. The sheer complexity and scope of this cascade challenges the development of experimental models of and effective treatments for cardiac arrest. Many experimental animal preparations have been developed to decipher the mechanisms of damage to vital internal organs following cardiac arrest and cardiopulmonary resuscitation(CPR), and to develop treatments to interrupt the lethal injury cascades. Porcine models of cardiac arrest and resuscitation offer several important advantages over other species, and outcomes in this large animal are readily translated to the clinical setting. This review summarizes porcine cardiac arrest-CPR models reported in the literature, describes clinically relevant phenomena observed during cardiac arrest and resuscitation in pigs, and discusses numerous methodological considerations in modeling cardiac arrest/CPR. Collectively, published reports show the domestic pig to be a suitable large animal model of cardiac arrest which is responsive to CPR, defibrillatory countershocks and medications, and yields extensive information to foster advances in clinical treatment of cardiac arrest.Brandon H Cherry Anh Q Nguyen Roger A Hollrah Albert H Olivencia-Yurvati Robert T Mallet 2015World Journal of Critical Care Medicine2015,4,1:2
16lntrathecal HIV- 1 envelope glycoprotein gp120 induces enhanced pain states mediated by spinal cord proinflammatory cytokines 显示文摘Milligan E D O'Connor K A Nguyen K T 2001J Neurosci2001,21,8:1
17Plasminogen activator inhibitor type 1 is a potential target in renal fibrogenesis显示文摘Rerolle JP Hertig A Nguyen G 2000Kidney Int2000,58,5:1
18Complex-shaped three-dimensional microstructures and photonic crystals generated in a polysiloxane polymer by two-photon microstereolithography显示文摘STRAUB M NGUYEN L H FAZLIC A 2004Optical Materials2004,27,3:1
19Effects 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 2000Applied Physics Letters2000,77,:1
20Multiple sender distributed video Streaming显示文摘Nguyen T Zakhor A 2004IEEE Transactions on Multimedia2004,6,2:1
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