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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
2Comprehensive 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 2010World Journal of Gastroenterology2010,16,25:14
3Review of the current targeted therapies for non-small-cell lung cancer显示文摘The last decade has witnessed the development of oncogene-directed targeted therapies that have significantly changed the treatment of non-small-cell lung cancer(NSCLC). In this paper we review the data demonstrating efficacy of gefitinib, erlotinib, and afatinib, which target the epidermal growth factor receptor(EGFR), and crizotinib which targets anaplastic lymphoma kinase(ALK). We discuss the challenge of acquired resistance to these small-molecular tyrosine kinase inhibitors and review promising agents which may overcome resistance, including the EGFR T790 Mtargeted agents CO-1686 and AZD9291, and the ALKtargeted agents ceritinib(LDK378), AP26113, alectinib(CH/RO5424802), and others. Emerging therapies directed against other driver oncogenes in NSCLC including ROS1, HER2, and BRAF are covered as well. The identification of specific molecular targets in a significant fraction of NSCLC has led to the personalized deployment of many effective targeted therapies, with more to come.Kim-Son H Nguyen Joel W Neal Heather Wakelee 2014World Journal of Clinical Oncology2014,5,4:13
4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
5A unique sequence in the N-terminal regulatory region controls the nuclear localization of KLF8 by cooperating with the C-terminal zinc-fingers显示文摘Kr 眉 p 像像素的因素 8 (KLF8 ) 抄写因素在房间周期前进起一个关键作用, oncogenic 转变,对间充质的转变和侵略上皮。然而,它的原子本地化信号(NLS ) 没被识别。有另外的 KLF monopartite NLS (mNLS ) 和 C2H2 锌手指(ZF ) 的 KLF8 份额,哪个被显示了是为一些另外的 KLF 的 NLS。在这份报告,用指导 PCR 的 mutagenesis 和 immunofluorescent 显微镜学,我们显示出 mNLSs,任何单个 ZF 的删除,或变化的那混乱 Zn2+ 有约束力或联系 DNA 主题没影响 KLF8 的原子本地化。删除 > 然而,从 C 终点的 1.5 ZF 引起了 KLF8 的细胞质的累积。令人惊讶地,氨基酸(aa ) 的删除 151-200 区域几乎从原子核消除了 KLF8。有 PKC 禁止者的 S165A, K171E 或 K171R 变化,或处理导致了部分细胞质的累积。Co-immunoprecipitation 证明 KLF8 与 importin- 交往了,这个相互作用要求了 ZF 主题。aa 1-150 或 201-261 区域的删除独自没改变原子本地化。BrdU 加入和 cyclin D1 倡导者酶试金作为野类型的 KLF8 证明在原子本地化的 KLF8 异种有缺陷者不能支持 DNA 合成或 cyclin D1 倡导者激活。一起拿,这些结果建议 KLF8 有二 NLS,一包围 S165 和 K171 并且另外的是二双人脚踏车 ZF,它为 KLF8 原子本地化和它的细胞的功能的规定是批评的。Tina S Mehta Heng Lu Xianhui Wang Alison M Urvalek Kim-Hang H Nguyen Farah Monzur Jojo D Hammond Jameson Q Ma Jihe Zhao 2009Cell Research2009,19,9:10
6Oxidative stress and extracellular matrices after hepatectomy and liver transplantation in rats显示文摘AIM:To investigate oxidative stress(OS)-mediated damage and the behavior of extracellular matrices in various rat models because shear stress with portal hypertension and cold ischemia/warm reperfusion injury trigger the liver regeneration cascade after surgery. These injuries also cause fatal liver damage.METHODS: Rats were divided into four groups according to the surgery performed: control; hepatectomy with 40% liver remnant(60% hepatectomy); orthotopic liver transplantation(OLT) with whole liver graft(100% OLT); and split OLT(SOLT) with 40% graft(40% SOLT). Survival was evaluated. Blood and liver samples were collected at 6 h after surgery. Biochemical and histopathological examinations were performed. OSinduced damage, 4-hydroxynonenal, ataxia-telangiectasia mutated kinase, histone H2AX, phosphatidylinositol 3-kinase(PI3K) and Akt were evaluated by western blotting. Behavior of extracellular matrices, matrix metalloproteinase(MMP)-9, MMP-2, tissue inhibitor of metalloproteinase(TIMP)-1 and TIMP-2 were also evaluated by western blotting and zymography. RESULTS: Although 100% OLT survived, 60% hepatectomy and 40% SOLT showed poor survival. Histopathological, immunohistological, biochemical and protein assays revealed that 60% hepatectomy, 100% OLT and 40% SOLT showed liver damage. PI3K and Akt were decreased in 60% hepatectomy and 40% SOLT. For protein expression, 40% SOLT showed differences in MMP-9, MMP-2 and TIMP-2. TIMP-1 showed differences in 60% hepatectomy and 40% SOLT. For protein activity, MMP-9 demonstrated significant differences in 60% hepatectomy, 100% OLT and 40% SOLT. CONCLUSION: Under conditions with an insufficient liver remnant, prevention of OS-induced damage via the Akt/PI3K pathway may be key to improve the postoperative course. MMP-9 may be also a therapeutic target after surgery.Tomohide Hori Shinji Uemoto Feng Chen Lindsay B Gardner Ann-Marie T Baine Toshiyuki Hata Takayuki Kogure Justin H Nguyen 2014World Journal of Hepatology2014,6,2:7
7Innate 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 2014Cellular & Molecular Immunology2014,11,5:7
8Distinguishing between parenchymal and anastomotic leakage at duct-to-mucosa pancreatic reconstruction in pancreaticoduodenectomy显示文摘瞄准:在胰腺的残余的 duct-to-mucosa 重建把吻合与实质的漏区分开来。方法:我们考察了与 end-to-side duct-to-mucosa pancreatojejunostomy (PJ ) 在 5/2000 和 12/2005 之间执行的 68 pancreaticod-uodenectomies 的图表。pancreatography 的结果,以及仙子胰腺的排水管体积,和淀粉酶层次被分析。结果:68 pancreatojejunostomies, 48 没由 pancreatography 有漏缝并且有低排水管的淀粉酶(正常) ;八没让 pancreatographic 漏,但是提高了排水管淀粉酶(实质的漏缝) ;并且 12 让 pancreatographic 漏并且提高了排水管淀粉酶(吻合漏缝) 。尽管在实质的排水管体积漏,组显著地在手术后的白天(邮政部门) 被提高 4,没有差别在邮政部门 7 点被发现。排水管淀粉酶水平不在邮政部门 4 点是显著地不同的。在邮政部门 7 点,相反, anastomotic 漏缝组显著地与正常和 parenchymal 漏缝组相比提高了排水管淀粉酶水平(14158 +/- 24083 IU/L 对 89 +/- 139 IU/L 和 1707 +/- 1515 IU/L,分别地 P = 0.012 ) 。结论:为在 pancreaticoduodenectomy 以后的胰腺的残余重建,胰腺的排水管淀粉酶铺平的 pancreatogram 和仙子的联合能被用来在胰腺的残余重建在实质的和吻合漏之间区分。Justin H Nguyen 2008World Journal of Gastroenterology2008,14,43:7
9Comparison of renal safety of tenofovir and entecavir in patients with chronic hepatitis B: Systematic review with meta-analysis显示文摘BACKGROUND Recently, the American Association for the Study of Liver Disease suggested no preference between tenofovir(TDF) and entecavir(ETV) regarding potential long-term risks of renal complications. Over the years, renal safety has become a critical concern in nucleos(t)ide analog-treated patients due to the long-term use of these drugs. However, existing studies do not show significant differences in renal dysfunction between these two drugs. Further, there is a paucity of studies comparing the long-term renal effects of TDF and ETV.AIM To investigate the effects of TDF and ETV on renal function, we performed systematic review and meta-analysis.METHODS Two investigators independently searched the Cochrane Library, MEDLINE, and Embase databases for randomized controlled trials and nonrandomized studies(NRSs) using the keywords 'CHB', 'Tenofovir', and 'Entecavir', and additional references were obtained from the bibliographies of relevant articles published through December 2017. The quality of each study was assessed using the Newcastle-Ottawa scale and the Grading of Recommendations Assessment,Development and Evaluation criteria. The primary outcome was the change in serum creatinine level in the TDF and ETV groups at baseline, 6 mo, 12 mo and24 mo.RESULTSNine NRSs comprising 2263 participants met the inclusion criteria. Changes in creatinine levels were higher in the TDF group than in the ETV group at 6 mo[mean difference(MD) = 0.03 mg/dL;95%CI: 0.02-0.04;I2 = 0%], 12 mo(MD =0.05 mg/dL;95%CI: 0.02-0.08;I2 = 78%), and 24 mo(MD = 0.07 mg/dL;95%CI:0.01-0.13;I2 = 93%). The change in estimated glomerular filtration rate(eGFR) was significantly higher in the TDF group than in the ETV group at 6 mo[standardized mean difference(SMD),-0.22;95%Cl:-0.36--0.08;I2 = 0%], 12 mo(SMD =-0.24;95%Cl:-0.43--0.05;I2 = 50%), and 24 mo(-0.35;95%Cl:-0.61--0.09;I2= 67%).CONCLUSION TDF statistically significantly increased serum creatinine levels and decreased the eGFR in 6-24 mo compared to ETV, with moderate to low quality of evidence.However, the differences are negligible.Hyo-Young Lee Hyunwoo Oh Chan-Hyuk Park Yee-Hui Yeo Mindie H Nguyen Dae-Won Jun 2019World Journal of Gastroenterology2019,25,23:6
10Nutritional care in hospitalized patients with chronic liver disease显示文摘AIM: To evaluate the practice of nutritional assessment and management of hospitalised patients with cirrhosis and the impact of malnutrition on their clinical outcome.METHODS: This was a retrospective cohort study on patients with liver cirrhosis consecutively admitted to the Department of Gastroenterology and Hepatology at the Royal Adelaide Hospital over 24 mo. Details were gathered related to the patients' demographics, disease severity, nutritional status and assessment, biochemistry and clinical outcomes. Nutritional status was assessed by a dietician and determined by subjective global assessment. Estimated energy and protein requirements were calculated by Simple Ratio Method. Intake was estimated from dietary history and/or food charts, and represented as a percentage of estimated daily requirements. Median duration of follow up was 14.9(0-41.4) mo. RESULTS: Of the 231 cirrhotic patients(167 male, age: 56.3 ± 0.9 years, 9% Child-Pugh A, 42% ChildPugh B and 49% Child-Pugh C), 131(57%) had formal nutritional assessment during their admission and 74(56%) were judged to have malnutrition. In-hospitalcaloric(15.6 ± 1.2 kcal/kg vs 23.7 ± 2.3 kcal/kg, P = 0.0003) and protein intake(0.65 ± 0.06 g/kg vs 1.01 ± 0.07 g/kg, P = 0.0003) was significantly reduced in patients with malnutrition. Of the malnourished cohort, 12(16%) received enteral nutrition during hospitalisation and only 6(8%) received ongoing dietetic review and assessment following discharge from hospital. The overall mortality was 51%, and was higher in patients with malnutrition compared to those without(HR = 5.29, 95%CI: 2.31-12.1; P < 0.001). CONCLUSION: Malnutrition is common in hospitalised patients with cirrhosis and is associated with higher mortality. Formal nutritional assessment, however, is inadequate. This highlights the need for meticulous nutritional evaluation and management in these patients.Dep K Huynh Shane P Selvanderan Hugh AJ Harley Richard H Holloway Nam Q Nguyen 2015World Journal of Gastroenterology2015,21,45:6
11Treatment modalities for hypersplenism in liver transplant recipients with recurrent hepatitis C显示文摘Hepatitis C is the most common indication for orthotopic liver transplantation in the United States. Unfortunately, hepatitis C recurs universally in the transplanted liver and is the major cause of decreased graft and patient survival. The combination therapy of interferon and ribavirin has been shown to be the most effective therapy for recurrent hepatitis C. However, pre-and post-transplant hypersplenism often precludes patients from receiving the antiviral therapy. Splenectomy and partial splenic embolization are the two invasive modalities that can correct the cytopenia associated with hypersplenism. In this report we review the two treatment options, their associated outcomes and complications.Lena Sibulesky Justin H Nguyen Ricardo Paz-Fumagalli C Burcin Taner Rolland C Dickson 2009World Journal of Gastroenterology2009,15,40:5
12Hepatocellular 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 2016World Journal of Gastroenterology2016,22,37:5
13Novel role of phosphodiesterase inhibitors in the management of end-stage heart failure显示文摘In advanced heart failure(HF), chronic inotropic therapy with intravenous milrinone, a phosphodiesterase Ⅲ inhibitor, is used as a bridge to advanced management that includes transplantation, ventricular assist device implantation, or palliation. This is especially true when repeated attempts to wean off inotropic support result in symptomatic hypotension, worsened symptoms, and/or progressive organ dysfunction. Unfortunately, patients in this clinical predicament are considered hemodynamically labile and may escape the benefits of guidelinedirected HF therapy. In this scenario, chronic milrinone infusion may be beneficial as a bridge to introduction of evidence based HF therapy. However, this strategy is not well studied, and in general, chronic inotropic infusion is discouraged due to potential cardiotoxicity that accelerates disease progression and proarrhythmic effects that increase sudden death. Alternatively, chronic inotropic support with milrinone infusion is a unique opportunity in advanced HF. This review discusses evidence that long-term intravenous milrinone support may allow introduction of beta blocker(BB) therapy. When used together, milrinone does not attenuate the clinical benefits of BB therapy while BB mitigates cardiotoxic effects of milrinone. In addition, BB therapy decreases the risk of adverse arrhythmias associated with milrinone. We propose that advanced HF patients who are intolerant to BB therapy may benefit from a trial of intravenous milrinone as a bridge to BB initiation. The discussed clinical scenarios demonstrate that concomitant treatment with milrinone infusion and BB therapy does not adversely impact standard HF therapy and may improve left ventricular function and morbidity associated with advanced HF.Abhishek Jaiswal Vinh Q Nguyen Thierry H Le Jemtel Keith C Ferdinand 2016World Journal of Cardiology2016,8,7:4
14Fecal lactoferrin accurately reflects mucosal inflammation in inflammatory bowel disease显示文摘BACKGROUND Studies have demonstrated a potential role for fecal biomarkers such as fecal calprotectin(FC)and fecal lactoferrin(FL)in monitoring inflammatory bowel diseases(IBD)-Crohn's disease(CD)and ulcerative colitis(UC).However,their correlation to endoscopic scores,disease severity and affected intestinal surface has not been extensively investigated.AIM To correlate FL,and for comparison white blood cell(WBC)and C-reactive protein(CRP),with endoscopic scores,disease extent and location in CD and UC.METHODS Retrospective analysis in 188 patients who had FL,CRP and WBC determined within 30 d of endoscopy.Disease location,disease extent(number of intestinal segments involved),disease severity(determined by endoscopic scores),timing of FL testing in relation to colonoscopy,as well as the use of effective fast acting medications(steroids and biologics)between colonoscopy and FL measurement,were recorded.RESULTS In 131 CD and 57 UC patients,both CRP and FL-but not WBC-distinguished disease severity(inactive,mild,moderate,severe).In patients receiving fastacting(steroids or biologics)treatment in between FL and colonoscopy,FL showed a higher correlation to endoscopic scores when tested before vs after the procedure(r=0.596,P<0.001,vs r=0.285,P=0.15 for the Simple Endoscopic Score for CD;and r=0.402,P=0.01 vs r=0.054 P=0.84 for Disease Activity Index).Finally,FL was significantly correlated with the diseased mucosal surface(colon-ileocolon>small bowel)and the number of inflamed colon segments.CONCLUSION FL and CRP separated disease severity categories with FL showing lower discriminating P-values.FL showed a close correlation with the involved mucosal surface and with disease extent and was more closely correlated to endoscopy when determined before the procedure–this indicating that inflammatory activity changes associated with therapy might be rapidly reflected by FL levels.FL can accurately and timely characterize intestinal inflammation in IBD.Marrieth G Rubio Kofi Amo-Mensah James M Gray Vu Q Nguyen Sam Nakat Douglas Grider Kim Love James H Boone Dario Sorrentino 2019World Journal of Gastrointestinal Pathophysiology2019,10,5:4
15Simple and reproducible hepatectomy in the mouse using the clip technique显示文摘AIM: To investigate the reliability of massive hepatectomy models by using clip techniques. METHODS: We analyzed anatomical findings in 100 mice following massive hepatectomy induced by liver reduction > 70%. The impact of various factors in the different models was also analyzed, including learning curves, operative time, survival curves, and histopathological findings.RESULTS: According to anatomical results, models with 75%, 80%, and 90% hepatectomy produced massive hepatectomy. Learning curves and operative times were most optimal with the clip technique. Each hepatectomy performed using the clip technique produced a reasonable survival curve, and there were no differences in histopathological findings between the suture and clip techniques. CONCLUSION: Massive hepatectomy by the clip technique is simple and can provide reliable and relevant data.Tomohide Hori Norifumi Ohashi Feng Chen Ann-Marie T Baine Lindsay B Gardner Toshiyuki Hata Shinji Uemoto Justin H Nguyen 2012World Journal of Gastroenterology2012,18,22:4
16Matrix metalloproteinase-9 contributes to parenchymal hemorrhage and necrosis in the remnant liver after extended hepatectomy in mice显示文摘AIM:To investigate the effect of matrix metalloproteinase-9(MMP-9) on the remnant liver after massive hepatectomy in the mouse.METHODS:Age-matched,C57BL/6 wild-type(WT),MMP-9(-/-),and tissue inhibitors of metalloproteinases(TIMP)-1(-/-) mice were used.The mice received 80%-partial hepatectomy(PH).Samples were obtained at 6 h after 80%-PH,and we used histology,immunohistochemical staining,western blotting analysis and zymography to investigate the effect of PH on MMP-9.The role of MMP-9 after PH was investigated using a monoclonal antibody and MMP inhibitor.RESULTS:We examined the remnant liver 6 h after 80%-PH and found that MMP-9 deficiency attenuated the formation of hemorrhage and necrosis.There were significantly fewer and smaller hemorrhagic and necrotic lesions in MMP-9(-/-) remnant livers compared with WT and TIMP-1(-/-) livers(P < 0.01),with no difference between WT and TIMP-1(-/-) mice.Serum alanine aminotransaminase levels were significantly lower in MMP-9(-/-) mice compared with those in TIMP-1(-/-) mice(WT:476 ± 83 IU/L,MMP-9(-/-):392 ± 30 IU/L,TIMP-1(-/-):673 ± 73 IU/L,P < 0.01).Western blotting and gelatin zymography demonstrated a lack of MMP-9 expression and activity in MMP-9(-/-) mice,which was in contrast to WT and TIMP-1(-/-) mice.No change in MMP-2 expression was observed in any of the study groups.Similar to MMP-9(-/-) mice,when WT mice were treated with MMP-9 monoclonal antibody or the synthetic inhibitor GM6001,hemorrhagic and necrotic lesions were significantly smaller and fewer than in control mice(P < 0.05).These results suggest that MMP-9 plays an important role in the development of parenchymal hemorrhage and necrosis in the small remnant liver.CONCLUSION:Successful MMP-9 inhibition attenuates the formation of hemorrhage and necrosis and might be a potential therapy to ameliorate liver injury after massive hepatectomy.Norifumi Ohashi Tomohide Hori Florence Chen Sura Jermanus Christopher B Eckman Akimasa Nakao Shinji Uemoto Justin H Nguyen 2012World Journal of Gastroenterology2012,18,19:3
17Bulk 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
18Proximal gastric response to small intestinal nutrients is abnormal in mechanically ventilated critically ill patients显示文摘瞄准:在非常有病的病人决定近似的胃的反应到小肠的营养素。方法:近似胃的活动性在 13 个非常有病的病人被测量(49.3 +/- 4.7 年) 并且 12 个健康志愿者(27.7 +/- 2.9 年) 用一种 barostat 技术。记录在基线被执行,在 60-min 期间 intra 十二指肠的注入保证(2 kcal/min ) ,并且为跟随注入的 2 h。最小的扩张压力(MDP ) , intra 袋子体积和底的波浪活动是坚定的。结果:MDP 在病人是更高的(11.7 +/- 1.1 对 7.8 +/- 0.7 毫米汞柱;P < 0.01 ) 。基线 intra 袋子体积在 2 个组是类似的。在健康题目,一“双性人形式”近似胃的体积反应被观察。在病人,近似胃的体积的起始的增加小、推迟,但是最后到达了类似于健康题目的最大的体积。在健康题目,近似胃的体积很快在滋养的注入以后回到了基线水平(中部 18 min ) 。相反,到基线的体积的恢复在非常有病的病人被推迟(中部 106 min ) 。在 6 个病人,体积没在滋养的注入以后回到基线水平 2 小时。在病人,底的体积波浪是不太经常的(P < 0.05 ) 并且有的更低的振幅(P < 0.001 ) ,与健康题目相比。结论:在重病,对小肠的滋养的刺激的近似胃的马达回答是反常的。Nam Q Nguyen Robert J Fraser Marianne Chapman Laura K Bryant Richard H Holloway Rosalie Vozzo Christine Feinle-Bisset 2006World Journal of Gastroenterology2006,12,27:3
19Proximal gastric motility in critically ill patients with type 2 diabetes mellitus显示文摘AIM: To investigate the proximal gastric motor response to duodenal nutrients in critically ill patients with long- standing type 2 diabetes mellitus. METHODS: Proximal gastric motility was assessed (using a barostat) in 10 critically ill patients with type 2 diabetes mellitus (59 ± 3 years) during two 60-min duodenal infusions of Ensure? (1 and 2 kcal/min), in random order, separated by 2 h fasting. Data were compared with 15 non-diabetic critically ill patients (48 ± 5 years) and 10 healthy volunteers (28 ± 3 years). RESULTS: Baseline proximal gastric volumes were similar between the three groups. In diabetic patients, proximal gastric relaxation during 1 kcal/min nutrient infusion was similar to non-diabetic patients and healthy controls. In contrast, relaxation during 2 kcal/ min infusion was initially reduced in diabetic patients (P < 0.05) but increased to a level similar to healthy humans, unlike non-diabetic patients where relaxation was impaired throughout the infusion. Duodenal nutrient stimulation reduced the fundic wave frequency in a dose-dependent fashion in both the critically ill diabetic patients and healthy subjects, but not in critically ill patients without diabetes. Fundic wave frequency in diabetic patients and healthy subjects was greater than in non-diabetic patients. CONCLUSION: In patients with diabetes mellitus, proximal gastric motility is less disturbed than non- diabetic patients during critical illness, suggesting that these patients may not be at greater risk of delayed gastric emptying.Nam Q Nguyen Robert J Fraser Laura K Bryant Marianne Chapman Richard H Holloway 2007World Journal of Gastroenterology2007,13,2:3
20Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in periodontal infection显示文摘Teng YT Nguyen H Gao X 2000J Clin Invest2000,106,6:2
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