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| 1 | Inhibition of the B7-H3 immune checkpoint limits tumor growth by enhancing cytotoxic lymphocyte function显示文摘在肿瘤和免疫系统之间的相互作用仍然糟糕被理解。重要临床的回答在对 CTLA4 和 PD-1/PD-L1 检查点与抗体对待的癌症病人被完成了;然而,仅仅病人的小部分对治疗作出回应,显示需要探索为癌症治疗的另外的 co 禁止的分子。B7-H3, B7 总科的一个成员,被我们以前显示出禁止 T 房间激活和 autoimmunity。在这研究,我们在肿瘤免疫分析了 B7-H3 的功能。B7-H3 的表示在多重肿瘤线,渗入肿瘤的树枝状的房间,和巨噬细胞被发现。与对抗抗体对待到 B7-H3 的 B7-H3-deficient 老鼠或老鼠显示出多重肿瘤的减少的生长,它取决于 NK 和 CD8 + T 房间。与细胞毒素的淋巴细胞表示的通常认为的受体, B7-H3 禁止了他们的激活,并且它的缺乏在忍受肿瘤的鼠标导致了增加的细胞毒素的淋巴细胞功能。B7-H3 和 PD-1 的联合封锁导致了迟了阶段的肿瘤的进一步提高的治疗学的控制。一起拿,我们的结果显示 B7-H3 检查点可以对癌症为免疫疗法用作一个新奇目标。 | Young-hee Lee Natalia Martin-Orozco Peilin Zheng Jing Li Peng Zhang Haidong Tan Hyun Jung Park Mira Jeong Seon Hee Chang Byung-Seok Kim Wei Xiong Wenjuan Zang Li Guo Yang Liu Zhong-jun Dong Willem W Overwijk Patrick Hwu Qing Yi Larry Kwak Zhiying Yang Tak W Mak Wei-Li Laszlo G Radvanyi Ling Ni Dongfang Liu Chen Dong | 2017 | Cell Research2017，27，8： | 29 |
| 2 | Characteristics of hepatocellular carcinoma in cirrhotic and non-cirrhotic non-alcoholic fatty liver disease显示文摘AIM: To determine characteristics and prognosticpredictors of patients with hepatocellular carcinoma(HCC) in association with non-alcoholic fatty liver disease(NAFLD).METHODS: We reviewed the records of all patients with NAFLD associated HCC between 2000 and 2012. Data collected included demographics; histology; presence or absence of cirrhosis, size and number of HCC, alpha-fetoprotein, body mass index(BMI), and the presence of diabetes, hypertension, or dyslipidaemia.RESULTS: Fifty-four patients with NAFLD associated HCC were identified. Mean age was 64 years with 87% male. Fifteen percent(8/54) were not cirrhotic. 11%, 24% and 50% had a BMI of < 25 kg/m2, 25-29 kg/m2 and ≥ 30 kg/m2 respectively. Fifty-nine percent were diabetic, 44% hypertensive and 26% hyperlipidaemic. Thirty-four percent of the patients had ≤ 1 of these risk factors. Non-cirrhotics had a significantly larger mean tumour diameter at diagnosis than cirrhotics(P = 0.041). Multivariate analysis did not identify any other patient characteristics that predicted the size or number of HCC.CONCLUSION: HCC can develop in NAFLD without cirrhosis. At diagnosis such tumours are larger than those in cirrhotics, conferring a poorer prognosis. | Christopher Leung Sern Wei Yeoh Desmond Patrick Shara Ket Kaye Marion Paul Gow Peter W Angus | 2015 | World Journal of Gastroenterology2015，21，4： | 24 |
| 3 | Blood glucose changes surrounding initiation of tumor-necrosis factor inhibitors and conventional disease-modifying anti-rheumatic drugs in veterans with rheumatoid arthritis显示文摘AIM To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi's, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs(DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation. Similar data were obtained for patients with proximate values available for glycosylated hemoglobin A1C values within a window 2 mo preceding, and 12 mo following, medication initiation. RBG and A1C measurements were compared before and after initiation events using paired t-tests, and multivariate regression analysis was performed including established comorbidities and demographics.RESULTS Two thousands one hundred and eleven patients contributed at least one proximate measurement surrounding the initiation of any examined medication. A significant decrease in RBG was noted surrounding 653 individual hydroxychloroquine-initiation events(-3.68 mg/dL, P = 0.04), while an increase was noted for RBG surrounding 665 prednisone-initiation events(+5.85 mg/d L, P < 0.01). A statistically significant decrease in A1C was noted for sulfasalazine initiation, as measured by 49 individual initiation events(-0.70%, P < 0.01). Multivariate regression analyses, using methotrexate as the referent, suggest sulfasalazine (β =-0.58, P = 0.01) and hydroxychloroquine(β =-5.78, P = 0.01) use as predictors of lower post-medicationinitiation RBG and A1C values, respectively. Analysis by drug class suggested prednisone (or glucocorticoids) as predictive of higher medication-initiation event RBG among all start events as compared to DMARDs, while this analysis did not show any drug class-level effect for TNFi. A diagnosis of congestive heart failure(β = 4.69, P = 0.03) was predictive for higher post-initiation RBG values among all medication-initiation events.CONCLUSION No statistically significant hypoglycemic effects surrounding TNFi initiation were observed in this large cohort. Sulfasalazine and hydroxychloroquine may have epidemiologically significant acute hypoglycemic effects. | Patrick R Wood Evan Manning Joshua F Baker Bryant England Lisa Davis Grant W Cannon Ted R Mikuls Liron Caplan | 2018 | World Journal of Diabetes2018，9，2： | 8 |
| 4 | 诊断性试验和策略的证据质量和推荐强度的分级显示文摘GRADE系统能对诊断性试验或策略的证据质量和推荐强度进行分级。本文旨在阐释在此过程中如何考虑患者的重要结局, | Holger J Schünemann Andrew D Oxman Jan Brozek Paul Glasziou Roman Jaeschke Gunn E Vist John W Williams Jr Regina Kunz Jonathan Craig Victor M Montori Patrick Bossuyt Gordon H Guyatt 李晓 黄程 陈耀龙 李幼平 | 2009 | 中国循证医学杂志2009，9，5： | 7 |
| 5 | Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-1igase signaling effector DWARF3显示文摘 | Li-Hua Zhao X Edward Zhou Wei Yi Zhongshan Wu Yue Liu Yanyong Kang Li Hou Parker W de Waal Suling Li Yi Jiang Adrian Scaffidi Gavin R Flematti Steven M Smith Vinh Q Lam Patrick R Griffin YonghongWang Jiayang Li Karsten Melcher H Eric Xu | 2015 | Cell Research2015，25，11： | 7 |
| 6 | Current application of proteomics in biomarker discoveryfor inflammatory bowel disease显示文摘Recently, the field of proteomics has rapidly expanded in its application towards clinical research with objectives ranging from elucidating disease pathogenesis to discovering clinical biomarkers. As proteins govern and/or reflect underlying cellular processes, the study of proteomics provides an attractive avenue for research as it allows for the rapid identification of protein profiles in a biological sample. Inflammatory bowel disease(IBD) encompasses several heterogeneous and chronic conditions of the gastrointestinal tract. Proteomic technology provides a powerful means of addressing major challenges in IBD today, especially for identifying biomarkers to improve its diagnosis and management. This review will examine the current state of IBD proteomics research and its use in biomarker research. Furthermore, we also discuss the challenges of translating proteomic research into clinically relevant tools. The potential application of this growing field is enormous and is likely to provide significant insights towards improving our future understanding and management of IBD. | Patrick PY Chan Valerie C Wasinger Rupert W Leong | 2016 | World Journal of Gastrointestinal Pathophysiology2016，7，1： | 5 |
| 7 | General competencies of problem‐based learning (PBL) and non‐PBL graduates显示文摘 | Katinka J A HPrince Patrick W L JVan Eijs Henny P ABoshuizen Cees P MVan Der Vleuten Albert J J AScherpbier | 2005 | Medical Education2005，，4： | 5 |
| 8 | 一种房颤风险评分系统的建立(Framingham心脏研究):基于社区的队列研究显示文摘背景房颤导致了发病率和病死率的显著上升。本研究旨在建立一种预测个体罹患房颤绝对风险的风险评分系统,并提供研究人员评价新危险因素的流程。方法作者评估了Framingham心脏研究中于1968年6月至1987年9月间进行了8044次检测的4764例参与者(55%为女性,年龄45~95岁)。此后,参与者被随访至房颤首发,随访期最长达10年。多变量Coxi回归确认出1(1年内罹患房颤的临床危险因素。次级分析纳入了常规超声心动图检测指标(5152例4参与者,7156次检测)对房颤风险进行再分层评估,并评价超声检测指标能否提高风险预测能力。结果4764例参与者中的457例4(10%)罹患房颤。年龄、性别、体重指数、收缩压、降压治疗、PR间期、有临床意义的心脏杂音及心力衰竭与房颤相关,并被纳入了风险评分模型(除体重指数P=0.08外,其余均为P〈0.05),模型的C统计量为0.78(95%CI0.76~0.80)。10年房颤风险随年龄变化:年龄〈65岁的人群中53例(1%)风险高于15%,而〉65岁的人群中为783例(27%)。为提高预测能力而纳入超声检测指标仅使模型C统计量略微增高,由0.78(95%C10.75~0.80)增至0.79(95%CI0.77~0.82:P=0.005)。超声心动图检测指标并不能改善风险再分层评估(P=0.18)。结论基于社区医疗中易得的临床因素建立的风险评分系统,有助于确认社区个体罹患房颤的风险,评估技术或标志物能否改善风险预测,以及针对高危个体采取预防措施。 | Renate B Schnabel Lisa M Sullivan Daniel Levy Michael J Pencina Joseph M Massaro Ralph B D'Agostino Sr Christopher Newton-Cheh Jennifer F Yamamoto Jared W Magnani Thomas M Tadros William B Kannel Thomas J Wang Patrick T Ellinor Philip A Wolf Ramachanclran S Vasan Emelia J Benjamin 黄刚(译) | 2009 | 世界临床医学2009，，9： | 2 |
| 9 | Analysis of the nitric oxide-cyclic guanosine monophosphate pathway in experimental liver cirrhosis suggests phosphodiesterase-5 as potential target to treat portal hypertension显示文摘AIM To investigate the potential effect of inhibitors of phosphodiesterase-5(PDE-5) for therapy of portal hypertension in liver cirrhosis.METHODS In the rat model of thioacetamide-induced liver fibrosis/cirrhosis the nitric oxide-cyclic guanosine monophosphate(NO-cGMP) pathway was investigated. Expression and localization of PDE-5, the enzyme that converts vasodilating cGMP into inactive 5'-GMP, was in the focus of the study. Hepatic gene expression of key components of the NO-cGMP pathway was determined by qRT-PCR: Endothelial NO synthase(eNOS), inducible NO synthase(iNOS), soluble guanylate cyclase subunits α1 and β1(sGCa1, sGCb1), and PDE-5. Hepatic PDE-5 protein expression and localization were detected by immunohistochemistry. Serum cGMP concentrations were measured using ELISA. Acute effects of the PDE-5 inhibitor Sildenafil(0.1 mg/kg or 1.0 mg/kg) on portal and systemic hemodynamics were investigated using pressure transducers.RESULTS Hepatic gene expression of eNOS(2.2-fold; P = 0.003), sGCa1(1.7-fold; P = 0.003), sGCb1(3.0-fold; P = 0.003), and PDE-5(11-fold; P = 0.003) was increased in cirrhotic livers compared to healthy livers. Overexpression of PDE-5(7.7-fold; P = 0.006) was less pronounced in fibrotic livers. iNOS expression was only detected in fibrotic and cirrhotic livers. In healthy liver, PDE-5 protein was localized primarily in zone 3 hepatocytes and to a lesser extent in perisinusoidal cells. This zonation was disturbed in cirrhosis: PDE-5 protein expression in perisinusoidal cells was induced approximately 8-fold. In addition, PDE-5-expressing cells were also found in fibrous septa. Serum cGMP concentrations were reduced in rats with cirrhotic livers by approximately 40%. Inhibition of PDE-5 by Sildenafil caused a significant increase in serum cGMP concentrations [+ 64% in healthy rats(P = 0.024), + 85% in cirrhotic rats(P = 0.018)]. Concomitantly, the portal venous pressure was reduced by 19% in rats with liver cirrhosis. CONCLUSION Overexpression and abrogated zonation of PDE-5 likely contribute to the pathogenesis of cirrhotic portal hypertension. PDE-5 inhibition may therefore be a reasonable therapeutic approach for portal hypertension. | Denise Schaffner Adhara Lazaro Peter Deibert Peter Hasselblatt Patrick Stoll Lisa Fauth Manfred W Baumstark Irmgard Merfort Annette Schmitt-Graeff Wolfgang Kreisel | 2018 | World Journal of Gastroenterology2018，24，38： | 2 |
| 10 | Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial显示文摘 | Friedrich W Mohr Marie-Claude Morice A Pieter Kappetein Ted E Feldman Elisabeth St?hle Antonio Colombo Michael J Mack David R Holmes Marie-angèle Morel Nic Van Dyck Vicki M Houle Keith D Dawkins Patrick W Serruys | 2013 | The Lancet . 2013 (9867)2013，，9867： | 2 |
| 11 | Simultaneous preperitoneal hernia repair duringradical pelvic surgery显示文摘 | Patrick C W | 1987 | J Urol1987，137，6： | 1 |
| 12 | Toward a unifying framework for exploring fit and flexibility in strategic human resource management显示文摘 | Patrick M W & Scott A S | 1998 | Academy of management review1998，23，： | 1 |
| 13 | Auxin-promoted transport of metabolites in stem of Phasevlus vulgaris L:auxin dose response curves and effects of inhibitors of polar auxin transport显示文摘 | Patrick J W Steains K H | 1987 | J Exp Bot1987，38，： | 1 |
| 14 | The carbon we do not see-the impact of low molecular weight compounds on carbon dynamics and respiration in forest soils:a review显示文摘 | PATRICK A W DAVID L J FINLAY R | 2005 | Soil Biology & Biochemistry2005，37，： | 1 |
| 15 | Influence of extractable iron, aluminum and manganese of P sorption in flooded acid sulfate soils 显示文摘 | Jugsujinda A Krairapanona A Patrick J R W H | 1995 | Biology and Fertility of Soils1995，20，： | 1 |
| 16 | Nitrogen and phosphorus distribution and utilization by Spartina alterniflora in a Louisiana gulf coastal marsh显示文摘 | BURESH R J DELAUNE R D PATRICK W H | 1980 | Estuaries and coasts1980，3，2： | 1 |
| 17 | Effect of alternate aerobic and anaerobic con- ditions on redox potential, organic matter decomposition and nitrogen loss in a flooded soil显示文摘 | Reddy K Patrick J W | 1975 | Soil Biol Biochem1975，7，2： | 1 |
| 18 | Preferred risk allocation in target cost contracts in con- struction显示文摘 | Joseph H L Chan Daniel W M Chan Patrick T I Lam | 2011 | Facilities2011，29，1314： | 1 |
| 19 | Optical propertiesof cubic SiC:luminescence of nitrogen-exciton complexes,and interband absorption显示文摘 | Choyke W J Hamilton D R Patrick L | 1964 | Physical Review1964，133，4： | 1 |
| 20 | Phloem unloading: Sieve element unloading and post - sieve element transport显示文摘 | PATRICK J W | 1997 | Annual Review of Plant Physiology and Plant Molecular Biology1997，28，： | 1 |
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