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| 1 | Portal vein thrombosis in cirrhosis: Controversies and latest developments显示文摘Portal vein thrombosis(PVT) is encountered in livercirrhosis, particularly in advanced disease. It has been a feared complication of cirrhosis, attributed to significant worsening of liver disease, poorer clinical outcomes and potential inoperability at liver transplantation; also catastrophic events such as acute intestinal ischaemia. Optimal management of PVT has not yet been addressed in any consensus publication.We review current literature on PVT in cirrhosis; its prevalence, pathophysiology, diagnosis, impact on the natural history of cirrhosis and liver transplantation,and management. Studies were identified by a search strategy using MEDLINE and Google Scholar. The incidence of PVT increases with increasing severity of liver disease: less than 1% in well-compensated cirrhosis, 7.4%-16% in advanced cirrhosis. Prevalence in patients undergoing liver transplantation is 5%-16%.PVT frequently regresses instead of uniform thrombus progression. PVT is not associated with increased risk of mortality. Optimal management has not been addressed in any consensus publication. We propose areas for future research to address unresolved clinical questions. | Damian J Harding M Thamara PR Perera Frederick Chen Simon Olliff Dhiraj Tripathi | 2015 | World Journal of Gastroenterology2015，21，22： | 42 |
| 2 | 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 |
| 3 | Current and future applications of magnetic resonance imaging and spectroscopy of the brain in hepatic encepha-lopathy显示文摘肝的脑病(他) 普通 neuro 精神病学的畸形,它从肝细胞失败或 portosystemic 与肝疾病和结果复杂化病人的功课正在推延。表明他是广泛地可变的并且从温和无临床症状的骚乱包含一个系列到深昏迷。研究兴趣集中于传播导出勇气的毒素的角色,特别地氨,胀大的大脑的开发和在导致全球 CNS 消沉和混乱功能的服的 neurotransmitter 系统的变化。直到最近,服的功能的直接调查有在人是困难的。然而,当磁性的回声光谱学( 1H 太太)检测的质子在大脑生物化学变化时,新磁性的回声成像( MRI )技术在大脑体积( coregistered MRI )和损害大脑功能( fMRI )提供对变化的评价的一个非侵略的工具,包括服的 osmolytes 的直接测量,例如 myoinositol ,充斥管理对细胞的动态平衡内在的过程的使挫折和夫酸安,包括细胞内部的水的累积。这些细胞内部的 osmolytes 的集中与 hyperammonaemia 改变。有 neuropsychiatric 缺陷并且自从先生系列的严厉的检测太太的代谢物畸形相互关联向正常术后疗法回来,技术可能具有在客观耐心的监视并且在估计各种各样的治疗政体的有效性的使用。 | VP Bob Graver M Alex Dresner Daniel M Forton Serena Counsell David J Larkman Nayna Patel Howard C Thomas Simon D Taylor-Robinson | 2006 | World Journal of Gastroenterology2006，12，19： | 8 |
| 4 | Dementia and osteoporosis in a geriatric population: Is there a common link?显示文摘AIM To determine the existence of a common pathological link between dementia and osteoporosis through reviewing the current evidence base. METHODS This paper reviews the current literature on osteoporosis and dementia in order to ascertain evidence of a common predisposing aetiology. A literature search of Ovid MEDLINE(1950 to June 2016) was conducted. The keywords 'osteoporosis', 'osteoporotic fracture', 'dementia' and 'Alzheimer's disease'(AD) were used to determine the theoretical links with the most significant evidence base behind them. The key links were found to be vitamins D and K, calcium, thyroid disease, statins, alcohol and sex steroids. These subjects were then searched in combination with the previous terms and the resulting papers manually examined. Theoretical, in vitro and in vivo research were all used to inform this review which focuses on the most well developed theoretical common causes for dementia(predominantly Alzheimer's type) and osteoporosis.RESULTS Dementia and osteoporosis are multifaceted disease processes with similar epidemiology and a marked increase in prevalence in elderly populations. The existence of a common link between the two has been suggested despite a lack of clear pathological overlap in our current understanding. Research to date has tended to be fragmented and relatively weak in nature with multiple confounding factors reflecting the difficulties of in vivo experimentation in the population of interest. Despite exploration of various possible mechanisms in search for a link between the two pathologies, this paper found that it is possible that these associations are coincidental due to the nature of the evidence available. One finding in this review is that prior investigation into common aetiologies has found raised amyloid beta peptide levels in osteoporotic bone tissue, with a hypothesis that amyloid beta disorders are systemic disorders resulting in differing tissue manifestations. However, our findings were that the most compelling evidence of a common yet independent aetiology lies in the APOE4 allele, which is a well-established risk for AD but also carries an independent association with fracture risk. The mechanism behind this is thought to be the reduced plasma vitamin K levels in individuals exhibiting the APOE4 allele which may be amplified by the nutritional deficiencies associated with dementia, which are known to include vitamins K and D. The vitamin theory postulates that malnutrition and reduced exposure to sunlight in patients with AD leads to vitamin deficiencies. CONCLUSION Robust evidence remains to be produced regarding potential links and regarding the exact aetiology of these diseases and remains relevant given the burden of dementia and osteoporosis in our ageing population. Future research into amyloid beta, APOE4 and vitamins K and D as the most promising aetiological links should be welcomed. | Candice L Downey Adam Young Emily F Burton Simon M Graham Robert J Macfarlane Eva-Maria Tsapakis Eleftherios Tsiridis | 2017 | World Journal of Orthopedics2017，8，5： | 6 |
| 5 | Evidence for the involvement of NOD2 in regulating colonic epithelial cell growth and survival显示文摘AIM: To investigate the function of NOD2 in colonic epithelial cells (CEC). METHODS: A combination of in vivo and in vitro analyses of epithelial cell turnover in the presence and absence of a functional NOD2 protein and, in response to enteric Salmonella typhimurium infection, were used. shRNA interference was also used to investigate the consequences of knocking down NOD2 gene expression on the growth and survival of colorectal carcinoma cell lines. RESULTS:In the colonic mucosa the highest levels of NOD2 expression were in proliferating crypt epithelial cells. Muramyl dipeptide (MDP), that is recognized by NOD2, promoted CEC growth in vitro . By contrast,the growth of NOD2-deficient CECs was impaired. In vivo CEC proliferation was also reduced and apoptosis increased in Nod2-/- mice, which were also evident following enteric Salmonella infection. Furthermore, neutralization of NOD2 mRNA expression in human colonic carcinoma cells by shRNA interference resulted in decreased survival due to increased levels of apoptosis. CONCLUSION: These findings are consistent with the involvement of NOD2 protein in promoting CEC growth and survival. Defects in proliferation by CECs in cases of CD may contribute to the underlying pathology of disrupted intestinal homeostasis and excessive inflammation. | Sheena M Cruickshank Louise Wakenshaw John Cardone Peter D Howdle Peter J Murray Simon R Carding | 2008 | World Journal of Gastroenterology2008，14，38： | 3 |
| 6 | Characterization of colonic dendritic cells in normal and colitic mice显示文摘AIM: Recent studies demonstrating the direct involvement of dendritic cells (DC) in the activation of pathogenic T cells in animal models of inflammatory bowel disease identify DC as important antigen presenting cells in the colon. However, very little is known about the properties of colonic DC.METHODS: Using immunohistochemistry, electron microscopy and flow cytometry we have characterized and compared colonic DC in the colon of healthy animals and interleukin-2-deficient (IL2-/-) mice that develop colitis.RESULTS: In the healthy colon, DC resided within the lamina propria and in close association with the basement membrane of colonic villi. Type 1 myeloid (CD11c+, CD11b+,B220-, CD8α-) DC made up the largest (40-45%) population and all DC expressed low levels of CD80, CD86, and CD40,and had high endocytic activity consistent with an immature phenotype. In colitic IL2-/- mice, colonic DC numbers increased four- to five-fold and were localized within the epithelial layer and within aggregates of T and B cells. They were also many more DC in mesenteric lymph nodes (MLN).The majority (>85%) of DC in the colon and MLN of IL2-/-mice were type 1 myeloid, and expressed high levels of MHC class Ⅱ, CD80, CD86, CD 40, DEC 205, and CCR5molecules and were of low endocytic activity consistent with mature DC.CONCLUSION: These findings demonstrate striking changes in the number, distribution and phenotype of DC in the inflamed colon. Their intimate association with lymphocytes in the colon and draining lymph nodes suggest that they may contribute directly to the ongoing inflammation in the colon. | Sheena M Cruickshank Nicholas R English Peter J Felsburg Simon R Carding | 2005 | World Journal of Gastroenterology2005，11，40： | 3 |
| 7 | Studies and characterisations of various activated carbons used for carbon/carbon supercapacitors显示文摘 | J Gamby P.L Taberna P Simon J.F Fauvarque M Chesneau | 2001 | Journal of Power Sources2001，，1： | 3 |
| 8 | Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm显示文摘 | Jeffrey Bethony Simon Brooker Marco Albonico Stefan M Geiger Alex Loukas David Diemert Peter J Hotez | 2006 | The Lancet2006，，9521： | 2 |
| 9 | Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial显示文摘 | Usha Chakravarthy Simon P Harding Chris A Rogers Susan M Downes Andrew J Lotery Lucy A Culliford Barnaby C Reeves | 2013 | The Lancet2013，，： | 2 |
| 10 | Management of venous thromboembolism in patients with advanced cancer: a systematic review and meta-analysis显示文摘 | Simon IR Noble Mike D Shelley Bernadette Coles Susan M Williams Andrew Wilcock Miriam J Johnson | 2008 | Lancet Oncology2008，，6： | 2 |
| 11 | Estimating the Global Public Health Implications of Electricity and Coal Consumption显示文摘 | Gohlke Julia M Thomas Reuben Woodward Alistair Campbell-Lendrum Diarmid Prüss-üstün Annette Hales Simon Portier Christopher J | 2011 | Environmental Health Perspectives2011，，6： | 2 |
| 12 | Podocin, a raft-associated compomnent of the glomemlar slit diaphragm interacts with CD2AP and nephrin 显示文摘 | Schwarz K Simons M Reiser J | 2001 | J Clin Invest2001，108，： | 1 |
| 13 | Longterm multiple color imaging of live cells using quantum dot bioconjugates 显示文摘 | Jaiswal J K Mattoussi H Mauro J M Simon S F | 2003 | Nature Biotechnolgy2003，21，： | 1 |
| 14 | The biological impact of mass-spectrometry-based proteomics 显示文摘 | Cravatt B F Simon G M Yates J R 3rd | 2007 | Nature2007，450，7172： | 1 |
| 15 | Ankle art hrodesis: long - term follow - up with gait analysis显示文摘 | Mazur J M Schuarle E Simon SR | 1979 | J Bone Joint Surg (Am)1979，61，： | 1 |
| 16 | Porous Cobalt(II)-organic frameworks with corrugated walls:structurally robust gas-sorption materials显示文摘 | Simon M H Chang J S Sung H J | 2007 | An-gew Chem Int Ed2007，46，12： | 1 |
| 17 | Description of ultrasonic vocalizations of the mouse lemur(Microcebus murinus)and the fat-tailed dwarf lemur ( Cheirogaleus medius) 显示文摘 | CHERRY J A IZARD M K SIMONS E | 1987 | Am J Primatol1987，13，： | 1 |
| 18 | Molecular screening for GS2lipase regula-tors:inhibition of keratinocyte retinylester hydrolysis by TIP47显示文摘 | Gao J G Simon M | 2006 | J Invest Dermatol2006，126，9： | 1 |
| 19 | N-terminal pro B-type natriuretic peptide as prognostic marker for mortality in coronary patients without clinically manifest heart failure显示文摘 | Mayer O Simon J Plaskova M | 2009 | Eur J Epidemiol2009，24，： | 1 |
| 20 | Long-term multiple color imaging of live cells using quantum dot bioconjugates显示文摘 | JAISWAL J K MATTOUSSI H D SIMON S M | 2003 | Nature Biotechnol2003，21，1： | 1 |
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