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| 1 | Cirrhotic portal hypertension: From pathophysiology to novel therapeutics显示文摘Portal hypertension and bleeding from gastroesophageal varices is the major cause of morbidity and mortality in patients with cirrhosis. Portal hypertension is initiated by increased intrahepatic vascular resistance and a hyperdynamic circulatory state. The latter is characterized by a high cardiac output, increased total blood volume and splanchnic vasodilatation, resulting in increased mesenteric blood flow. Pharmacological manipulation of cirrhotic portal hypertension targets both the splanchnic and hepatic vascular beds. Drugs such as angiotensin converting enzyme inhibitors and angiotensin Ⅱ type receptor 1 blockers, which target the components of the classical renin angiotensin system(RAS), are expected to reduce intrahepatic vascular tone by reducing extracellular matrix deposition and vasoactivity of contractile cells and thereby improve portal hypertension. However, these drugs have been shown to produce significant offtarget effects such as systemic hypotension and renal failure. Therefore, the current pharmacological mainstay in clinical practice to prevent variceal bleeding and improving patient survival by reducing portal pressure is non-selective-blockers(NSBBs). These NSBBs work by reducing cardiac output and splanchnic vasodilatation but most patients do not achieve an optimal therapeutic response and a significant proportion of patients are unable to tolerate these drugs.Although statins, used alone or in combination with NSBBs, have been shown to improve portal pressure and overall mortality in cirrhotic patients, further randomized clinical trials are warranted involving larger patient populations with clear clinical end points. On the other hand, recent findings from studies that have investigated the potential use of the blockers of the components of the alternate RAS provided compelling evidence that could lead to the development of drugs targeting the splanchnic vascular bed to inhibit splanchnic vasodilatation in portal hypertension. This review outlines the mechanisms related to the pathogenesis of portal hypertension and attempts to provide an update on currently available therapeutic approaches in the management of portal hypertension with special emphasis on how the alternate RAS could be manipulated in our search for development of safe, specific and effective novel therapies to treat portal hypertension in cirrhosis. | Lakmie S Gunarathne Harinda Rajapaksha Nicholas Shackel Peter W Angus Chandana B Herath | 2020 | World Journal of Gastroenterology2020，26，40： | 24 |
| 2 | An epigenomic approach to therapy for tamoxifen-resistant breast cancer显示文摘Tamoxifen 是为雌激素受体 alpha 的前线治疗(ERα) 在绝经前的女人的积极的胸肿瘤。然而,到 tamoxifen 的抵抗发生在许多病人。嗯仍然与获得的 tamoxifen 抵抗在乳癌房间的生长起一个关键作用,建议那 ERα为治疗仍然是一个有效目标 tamoxifen 抵抗(Tam-R ) 乳癌。以识别 ERα 的新奇管理者;发信号,通过对 histone 甲基修饰词的一幅小规模的 siRNA 屏幕,我们发现了 WHSC1, histone H3K36 methyltransferase, ERα 的一个积极管理者;在乳癌房间发信号。我们证明 WHSC1 被招募到 ERα由 BET 蛋白质 BRD3/4 的基因,并且便于 ERα基因表示。小分子的赌注蛋白质禁止者 JQ1 potently 压制了经典 ERα发信号的小径和在文化的 Tam-R 乳癌房间的生长。用一个 Tam-R 乳癌异种皮移植老鼠模型,我们与 JQ1 和 ER degrader fulvestrant 由 JQ1 和联合治疗的强壮的长持续的效果在 vivo 反胸癌症活动示威了。一起拿,我们提供 epigenomic 蛋白质 BRD3/4 和 WHSC1 是雌激素受体发信号的必要管理者并且是为 Tam-R 乳癌的治疗的新奇治疗学的目标的证据。 | Qin Feng Zheng Zhang Martin J Shea Chad J Creighton Cristian Coarfa Susan G Hilsenbeck Rainer Lanz Bin He Lei Wang Xiaoyong Fu Agostina Nardone Yongcheng Song James Bradner Nicholas Mitsiades Constantine S Mitsiades C Kent Osborne Rachel Schiff Bert W O'Malley | 2014 | Cell Research2014，24，7： | 10 |
| 3 | Factor analysis identifies subgroups of constipation显示文摘AIM:To determine whether distinct symptom groupings exist in a constipated population and whether such grouping might correlate with quantifiable pathophysiological measures of colonic dysfunction.METHODS:One hundred and ninety-one patients presenting to a Gastroenterology clinic with constipation and 32 constipated patients responding to a newspaper advertisement completed a 53-item,wide-ranging selfreport questionnaire.One hundred of these patients had colonic transit measured scintigraphically.Factor analysis determined whether constipation-related symptoms grouped into distinct aspects of symptomatology.Cluster analysis was used to determine whether indi-vidual patients naturally group into distinct subtypes.RESULTS:Cluster analysis yielded a 4 cluster solution with the presence or absence of pain and laxative unresponsiveness providing the main descriptors.Amongst all clusters there was a considerable proportion of patients with demonstrable delayed colon transit,irritable bowel syndrome positive criteria and regular stool frequency.The majority of patients with these characteristics also reported regular laxative use.CONCLUSION:Factor analysis identified four constipation subgroups,based on severity and laxative unresponsiveness,in a constipated population.However,clear stratification into clinically identifiable groups remains imprecise. | Philip G Dinning Mike Jones Linda Hunt Sergio E Fuentealba Jamshid Kalanter Denis W King David Z Lubowski Nicholas J Talley Ian J Cook | 2011 | World Journal of Gastroenterology2011，17，11： | 3 |
| 4 | CD133 expression is not restricted to stem cells, and both CD133^sup +^ and CD133^sup -^ metastatic colon cancer cells initiate tumors显示文摘 | Shmelkov Sergey V Butler Jason M Hooper Andrea T Hormigo Adilia Kushner Jared Milde Till Clair Ryan St Baljevic Muhamed White Ian Jin David K Chadburn Amy Murphy Andrew J Valenzuela David M Gale Nicholas W Thurston Gavin Yancopoulos George | 2008 | Journal of Clinical Investigation2008，，： | 2 |
| 5 | DNA vaccination of infants in the presence of maternal antibody: a measles model in the primate显示文摘 | Mary Premenko-Lanier Paul A Rota Gary Rhodes David Verhoeven Dan H Barouch Nicholas W Lerche Norman L Letvin William J Bellini Michael B McChesney | 2003 | Virology2003，，1： | 2 |
| 6 | Tumor targeted mesoporous silica-coated gold nanorods facilitate detection of pancreatic tumors using Multispectral optoacoustic tomography显示文摘Multispectral optoacoustic 断层摄影术(MSOT ) 是在传统的形式上提供几个优点的一种新兴的成像技术,特别地处于它解决在显微镜的规模上的深度的光对比的能力。当潜在的应用包括临床的阀值由当前的技术设置了的下面的肿瘤的早察觉时,肿瘤特定的对比代理人的缺乏限制 MSOT 成像的使用。因此,我们与 polyacrylic 酸(泛美航空公司) 或 aminefunctionalized mesoporous 硅石(MS ) 由涂层金牌 nanorods (GNR ) 构造了高度稳定的 nano 对比代理人。Syndecan-1,被显示了指向像胰岛素的生长因素 1 受体(IGF1-R )( 在胰腺的肿瘤的 upregulated ) ,在泛美航空公司涂的 GNR (PAA-GNRs ) 或 MS 涂的 GNR (MS-GNRs ) 的表面上被结合创造指向肿瘤的 nanoparticles。在 vitro, nanoparticles 指向的肿瘤与流动 cytometry 被估计。在 S2VP10L 房间(为 IGF1-R 积极) , syndecan-1 MS-GNRs (Syndecan-MS-GNRs ) 在 OA 信号表明了增加, 10x,与 syndecan-1 PAAGNR (Syndecan-PAA-GNRs ) 相比。最小的绑定在 MiaPaca-2 房间被观察(为 IGF1-R 否定) 。在 vivo,肿瘤 Syndecan-MS-GNRs 的特定的指向用鼠科的 orthotopic 被评估胰腺的癌症模型。Syndecan- MS-GNRs 比在象肝那样的离开目标机关在胰腺的肿瘤以内表明了显著地更大的累积。与 IGF1-R 否定 MiaPaca-2 房间植入的老鼠没表明指向的特定的肿瘤。在摘要,我们报导指向的 nano 对比代理人(Syndecan-MS-GNRs ) 能成功地检测 orthotopic 有在用 MSOT 的 vivo 有约束力的最小的离开目标的胰腺的肿瘤。 | Anil Khanal Christopher Ullum Charles W Kimbrough Nichola C. Garbett Joseph A. Burlison Molly W. McNally Phillip Chuong Ayman S. EI-Baz Jacek B. Jasinski Lacey R. McNally | 2015 | Nano Research2015，8，12： | 2 |
| 7 | Perioperative risk factors associated with delayed graft function following deceased donor kidney transplantation:A retrospective,single center study显示文摘BACKGROUND There is an abundant need to increase the availability of deceased donor kidney transplantation(DDKT)to address the high incidence of kidney failure.Challenges exist in the utilization of higher risk donor organs into what appears to be increasingly complex recipients;thus the identification of modifiable risk factors associated with poor outcomes is paramount.AIM To identify risk factors associated with delayed graft function(DGF).METHODS Consecutive adults undergoing DDKT between January 2016 and July 2017 were identified with a study population of 294 patients.The primary outcome was the occurrence of DGF.RESULTS The incidence of DGF was 27%.Under logistic regression,eight independent risk factors for DGF were identified including recipient body mass index≥30 kg/m^(2),baseline mean arterial pressure<110 mmHg,intraoperative phenylephrine administration,cold storage time≥16 h,donation after cardiac death,donor history of coronary artery disease,donor terminal creatinine≥1.9 mg/dL,and a hypothermic machine perfusion(HMP)pump resistance≥0.23 mmHg/mL/min.CONCLUSION We delineate the association between DGF and recipient characteristics of preinduction mean arterial pressure below 110 mmHg,metabolic syndrome,donorspecific risk factors,HMP pump parameters,and intraoperative use of phenylephrine. | Nicholas V Mendez Yehuda Raveh Joshua J Livingstone Gaetano Ciancio Giselle Guerra George W Burke III Vadim B Shatz Fouad G Souki Linda J Chen Mahmoud Morsi Jose M Figueiro Tony M Ibrahim Werviston L DeFaria Ramona Nicolau-Raducu | 2021 | World Journal of Transplantation2021，11，4： | 2 |
| 8 | Friction stir welding for the transportation industries 显示文摘 | Thomas W M Nicholas E D | 1997 | Materials and Design1997，18，6： | 1 |
| 9 | 显示文摘 | Alan D W Nicholas HH Yewlan W | 1999 | EMBO J1999，18，8： | 1 |
| 10 | Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip显示文摘 | WEINSTEIN R S NICHOLAS R W MANOLAGAS S C | 2000 | J Clin Endocrinol Metab2000，85，8： | 1 |
| 11 | Autoantigen based vac- cines for type 1 diabetes显示文摘 | Nicholas D Odumosu O Langridge W H | 2011 | Discov Med2011，11，59： | 1 |
| 12 | Cole Novel Approach of Medialization Thyroplasty with Arytenoid Adduction Performed under General Anesthesia with a Laryngeal Mask显示文摘 | Nicholas W Stow Jennifer W.Lee Ian E | | 0，，02： | 1 |
| 13 | Structural and mechanistic investigation of a phosphatemodified HZSM-5 catalyst for methanol conversion显示文摘 | Abubakar S M Marcus D M Lee J C Ehresmann J O Chen C Y Kletnieks P W Guenther D R Hayman M J Pavlova M Nicholas J B Haw J F | | 0，，10： | 1 |
| 14 | Field and laboratory studies of Desmodora cazca Gerlach,1956 (Desmodoridae:Nematoda) from mangrove mud-flats显示文摘 | Nicholas W L Stewart A C Marples T G | 1988 | Nematologica1988，34，3： | 1 |
| 15 | Friction processes benefit from a gas shied显示文摘 | Thomas W M Dave Nicholas Richard Wiktorgwiz | 1998 | Welding & Metal Fabrication1998，，5： | 1 |
| 16 | Plant antitumor agents(29): Synthesis and biological activity of ring D and ring E modified analogues of camptothecin显示文摘 | Nicholas A W Wani M C Manikumar G | 1990 | J Med Chem1990，33，3： | 1 |
| 17 | Prevalence and Predictors of Acute Stress Disorder and PTSD Following Road Traffic Accidents:Thought Control Strategies and Social Support:Special Series:On Understanding the Persistence of Depressive and Anxious Thinking显示文摘 | Vassiliki H Nicholas T Adrian W | 2001 | Behav Ther(S0005-7894)2001，32，1： | 1 |
| 18 | Intelligent agents:theory and practice显示文摘 | Michael W Nicholas R J | 1995 | Knowledge Engineering1995，10，2： | 1 |
| 19 | Friction stir welding for thetrans- portation industries 显示文摘 | Thomas W M Nicholas E D | 1997 | Materials and Design1997，18，： | 1 |
| 20 | The determination of glycogenin live rand muscle by use of athrone reagent显示文摘 | Nicholas V Carroll Robert W | | The Journalof Biologicalchemistry0，，： | 1 |
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