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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 | Treatment of meniscal tears: An evidence based approach显示文摘Treatment options for meniscal tears fall into three broad categories;non-operative,meniscectomy or meniscal repair.Selecting the most appropriate treatment for a given patient involves both patient factors(e.g.,age,co-morbidities and compliance)and tear characteristics(e.g.,location of tear/age/reducibility of tear).There is evidence suggesting that degenerative tears in older patients without mechanical symptoms can be effectively treated non-operatively with a structured physical therapy programme as a first line.Even if these patients later require meniscectomy they will still achieve similar functional outcomes than if they had initially been treated surgically.Partial meniscectomy is suitable for symptomatic tears not amenable to repair,and can still preserve meniscal function especially when the peripheral meniscal rim is intact.Meniscal repair shows 80%success at 2 years and is more suitable in younger patients with reducible tears that are peripheral(e.g.,nearer the capsular attachment)and horizontal or longitudinal in nature.However,careful patient selection and repair technique is required with good compliance to post-operative rehabilitation,which often consists of bracing and non-weight bearing for 4-6 wk. | Simon C Mordecai Nawfal Al-Hadithy Howard E Ware Chinmay M Gupte | 2014 | World Journal of Orthopedics2014，5，3： | 18 |
| 4 | Current status and recent advances of liver transplantation from donation after cardiac death显示文摘The last decade saw increased organ donation activity from donors after cardiac death (DCD). This contributed to a signif icant proportion of transplant activity. Despite certain drawbacks, liver transplantation from DCD donors continues to supplement the donor pool on the backdrop of a severe organ shortage. Understanding the pathophysiology has provided the basis for modulation of DCD organs that has been proven to be effective outside liver transplantation but remains experimental in liver transplantation models. Research continues on how best to further increase the utility of DCD grafts. Most of the work has been carried out exploring the use of organ preservation using machine assisted perfusion. Both ex-situ and in-situ organ perfusion systems are tested in the liver transplantation setting with promising results. Additional techniques involved pharmacological manipulation of the donor, graft and the recipient. Ethical barriers and end-of-life care pathways are obstacles to widespread clinical application of some of the recent advances to practice. It is likely that some of the DCD offers are in fact probably 'prematurely' of-fered without ideal donor management or even prior to brain death being established. The absolute benef its of DCD exist only if this form of donation supplements the existing deceased donor pool; hence, it is worthwhile revisiting organ donation process enabling us to identify counter remedial measures. | M Thamara PR Perera Simon R Bramhall | 2011 | World Journal of Gastrointestinal Surgery2011，3，11： | 16 |
| 5 | New aspects in the pathomechanism and diagnosis of the laryngopharyngeal reflux-clinical impact of laryngeal proton pumps and pharyngeal p H metry in extraesophageal gastroesophageal reflux disease显示文摘AIM:To determine the laryngeal H+K+-ATPase and pharyngeal p H in patients with laryngopharyngeal reflux(LPR)-symptoms as well as to assess the symptom scores during PPI therapy.METHODS:Endoscopy was performed to exclude neoplasia and to collect biopsies from the posterior cricoid area(immunohistochemistry and PCR analysis).Immunohistochemical staining was performed with monoclonal mouse antibodies against human H+K+-ATPase.Quantitative real-time RT-PCR for each of the H+K+-ATPase subunits was performed.The p H values were assessed in the aerosolized environment of the oropharynx(Dxp H Catheter) and compared to a subsequently applied combined p H/MII measurement.RESULTS:Twenty patients with LPR symptoms were included.In only one patient,the laryngeal H+K+-ATPase was verified by immunohistochemical staining.In another patient,real-time RT-PCR for each H+K+-ATPase subunit was positive.Fourteen out of twenty patients had pathological results in Dxp H,and 6/20 patients had pathological results in p H/MII.Four patients had pathological results in both functional tests.Nine out of twenty patients responded to PPIs.CONCLUSION:The laryngeal H+K+-ATPase can only be sporadically detected in patients with LPR symptoms and is unlikely to cause the LPR symptoms.Alternative hypotheses for the pathomechanism are needed.The role of pharyngeal p H-metry remains unclearand its use can only be recommended for patients in a research study setting. | Valentin Becker Romina Drabner Simone Graf Christoph Schlag Simon Nennstiel Anna Maria Buchberger Roland M Schmid Dieter Saur Monther Bajbouj | 2015 | World Journal of Gastroenterology2015，21，3： | 14 |
| 6 | Hepatocellular carcinoma: Review of disease and tumor biomarkers显示文摘Hepatocellular carcinoma(HCC) is a common malignancy and now the second commonest global cause of cancer death. HCC tumorigenesis is relatively silent and patients experience late symptomatic presentation. As the option for curative treatments is limited to early stage cancers, diagnosis in non-symptomatic individuals is crucial. International guidelines advise regular surveillance of high-risk populations but the current tools lack sufficient sensitivity for early stage tumors on the background of a cirrhotic nodular liver. A number of novel biomarkers have now been suggested in the literature, which may reinforce the current surveillance methods. In addition, recent metabonomic and proteomic discoveries have established specific metabolite expressions in HCC, according to Warburg's phenomenon of altered energy metabolism. With clinical validation, a simple and non-invasive test from the serum or urine may be performed to diagnose HCC, particularly benefiting low resource regions where the burden of HCC is highest. | Jin Un Kim Mohamed I F Shariff Mary M E Crossey Maria Gomez-Romero Elaine Holmes I Jane Cox Haddy K S Fye Ramou Njie Simon D Taylor-Robinson | 2016 | World Journal of Hepatology2016，8，10： | 13 |
| 7 | Global kinematics of tectonic plates and subduction zones since the late Paleozoic Era显示文摘Detailed global plate motion models that provide a continuous description of plate boundaries through time are an effective tool for exploring processes both at and below the Earth's surface. A new generation of numerical models of mantle dynamics pre-and post-Pangea timeframes requires global kinematic descriptions with full plate reconstructions extending into the Paleozoic(410 Ma). Current plate models that cover Paleozoic times are characterised by large plate speeds and trench migration rates because they assume that lowermost mantle structures are rigid and fixed through time. When used as a surface boundary constraint in geodynamic models, these plate reconstructions do not accurately reproduce the present-day structure of the lowermost mantle. Building upon previous work, we present a global plate motion model with continuously closing plate boundaries ranging from the early Devonian at 410 Ma to present day.We analyse the model in terms of surface kinematics and predicted lower mantle structure. The magnitude of global plate speeds has been greatly reduced in our reconstruction by modifying the evolution of the synthetic Panthalassa oceanic plates, implementing a Paleozoic reference frame independent of any geodynamic assumptions, and implementing revised models for the Paleozoic evolution of North and South China and the closure of the Rheic Ocean. Paleozoic(410-250 Ma) RMS plate speeds are on average ~8 cm/yr, which is comparable to Mesozoic-Cenozoic rates of ~6 cm/yr on average.Paleozoic global median values of trench migration trend from higher speeds(~2.5 cm/yr) in the late Devonian to rates closer to 0 cm/yr at the end of the Permian(~250 Ma), and during the Mesozoic-Cenozoic(250-0 Ma) generally cluster tightly around ~1.1 cm/yr. Plate motions are best constrained over the past 130 Myr and calculations of global trench convergence rates over this period indicate median rates range between 3.2 cm/yr and 12.4 cm/yr with a present day median rate estimated at~5 cm/yr. For Paleozoic times(410-251 Ma) our model results in median convergence rates largely~5 cm/yr. Globally,~90% of subduction zones modelled in our reconstruction are determined to be in a convergent regime for the period of 120-0 Ma. Over the full span of the model, from 410 Ma to 0 Ma,~93% of subduction zones are calculated to be convergent, and at least 85% of subduction zones are converging for 97% of modelled times. Our changes improve global plate and trench kinematics since the late Paleozoic and our reconstructions of the lowermost mantle structure challenge the proposed fixity of lower mantle structures, suggesting that the eastern margin of the African LLSVP margin has moved by as much as ~1450 km since late Permian times(260 Ma). The model of the plate-mantle system we present suggests that during the Permian Period, South China was proximal to the eastern margin of the African LLSVP and not the western margin of the Pacific LLSVP as previous thought. | Alexander Young Nicolas Flament Kayla Maloney Simon Williams Kara Matthews Sabin Zahirovic R.Dietmar Müller | 2019 | Geoscience Frontiers2019，10，3： | 10 |
| 8 | 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 |
| 9 | 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 |
| 10 | Esophageal tissue engineering:A new approach for esophageal replacement显示文摘A number of congenital and acquired disorders require esophageal tissue replacement.Various surgical techniques,such as gastric and colonic interposition,are standards of treatment,but frequently complicated by stenosis and other problems.Regenerative medicine approaches facilitate the use of biological constructs to replace or regenerate normal tissue function.We review the literature of esophageal tissue engineering,discuss its implications,compare the methodologies that have been employed and suggest possible directions for the future.Medline,Embase,the Cochrane Library,National Research Register and ClinicalTrials.gov databases were searched with the following search terms:stem cell and esophagus,esophageal replacement,esophageal tissue engineering,esophageal substitution.Reference lists of papers identified were also examined and experts in this field contacted for further information.All full-text articles in English of all potentially relevant abstracts were reviewed.Tissue engineering has involved acellular scaffolds that were either transplanted with the aim of being repopulated by host cells or seeded prior to transplantation.When acellular scaffolds were used to replace patch and short tubular defects they allowed epithelial and partial muscular migration whereas when employed for long tubular defects the results were poor leading to an increased rate of stenosis and mortality.Stenting has been shown as an effective means to reduce stenotic changes and promote cell migration,whilst omental wrapping to induce vascularization of the construct has an uncertain benefit.Decellularized matrices have been recently suggested as the optimal choice for scaffolds,but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution.Results in animal models that have used seeded scaffolds strongly suggest that seeding of both muscle and epithelial cells on scaffolds prior to implantation is a prerequisite for complete esophageal replacement.Novel approaches need to be designed to allow for peristalsis and vascularization in the engineered esophagus.Although esophageal tissue engineering potentially offers a real alternative to conventional treatments for severe esophageal disease,important barriers remain that need to be addressed. | Giorgia Totonelli Panagiotis Maghsoudlou Jonathan M Fishman Giuseppe Orlando Tahera Ansari Paul Sibbons Martin A Birchall Agostino Pierro Simon Eaton Paolo De Coppi | 2012 | World Journal of Gastroenterology2012，18，47： | 5 |
| 11 | Recurrent ectopic pancreatitis of the jejunum and mesentery over a 30-year period显示文摘BACKGROUND:Ectopic pancreas is defined as pancreatic tissue found outside its usual anatomical position,with no ductal or vascular communication with the native pancreas. We describe a case of ectopic pancreas of the small bowel and mesentery causing recurrent episodes of pancreatitis, initially suspected on computed tomography(CT)and magnetic resonance cholangiopancreatography(MRCP),and confirmed on histological review of the resection. METHODS:A 67-year-old woman presented with clinical symptoms and biochemical evidence of pancreatitis.She had similar episodes over the past 30 years with unrevealing investigations,and was concluded to have idiopathic pancreatitis. She underwent CT and MRCP,with findings suggestive of ectopic pancreas,a diagnosis confirmed on histology of the resection. RESULTS:MRCP identified a mass in the proximal small bowel mesentery isointense to the native pancreas,with a small duct draining into a proximal jejunal loop.The resected specimen consisted of normal parenchyma with lobulated acinar tissue with scattered islets of Langerhans,an occasional ductular structure,and admixed areas of adipose tissue.The patient remained asymptomatic with normal biochemistry six months post-operatively. CONCLUSION:In an individual with abdominal pain,elevated serum amylase/lipase,but imaging findings of a normal native pancreas,ectopic pancreatitis should be considered,and can be evaluated by CT and MRCP. | John CT Wong Charlotte Robinson Edward C Jones Alison Harris Charles Zwirewich Robert Wakefield Richard K Simons Eric M Yoshida | 2011 | Hepatobiliary & Pancreatic Diseases International2011，10，2： | 4 |
| 12 | Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion显示文摘Ischaemia-reperfusion injury(IRI) is the leading cause of injury seen in the liver following transplantation. IRI also causes injury following liver surgery and haemodynamic shock. The first cells within the liver to be injured by IRI are the liver sinusoidal endothelial cells(LSEC). Recent evidence suggests that LSEC coordinate and regulates the livers response to a variety of injuries. It is becoming increasingly apparent that the cyto-protective cellular process of autophagy is a key regulator of IRI. In particular LSEC autophagy may be an essential gatekeeper to the development of IRI. The recent availability of liver perfusion devices has allowed for the therapeutic targeting of autophagy to reduce IRI. In particular normothermic machine liver perfusion(NMP-L) allow the delivery of pharmacological agents to donor livers whilst maintaining physiological temperature and hepatic flow rates. In this review we summarise the current understanding of endothelial autophagy and how this may be manipulated during NMP-L to reduce liver IRI. | Yuri L Boteon Richard Laing Hynek Mergental Gary M Reynolds Darius F Mirza Simon C Afford Ricky H Bhogal | 2017 | World Journal of Gastroenterology2017，23，48： | 4 |
| 13 | Enemy at the gates: dendritic cells and immunity to mucosal pathogens显示文摘树枝状的房间(DC ) 是用作在天生、适应的免疫之间的一座必要的桥的多样、专业化的造血的房间。DC 在淋巴的所有和 nonlymphoid 机关存在并且在到在包括 mucosal 纸巾的上皮的表面的感染的第一个应答者之中。肺,内脏,和阴道 mucosa 显示的 DC 反映各独特的织物的不同显型和功能并且与他们在怒气和淋巴节点的对应物相对照,常常暴露于他们的环境的有害、良性的因素。Mucosal DC 认出并且通过模式识别的约会回答受体,和激活的 DC 移居到排干淋巴节点导致适应有免疫力的回答到病原体。DC 的专业化函数在 mucosa 帮助免疫和病原体控制的正式就职。如此的专门化包括有势力到病毒的 nucleic 酸,到在内脏腔的俘获有机体的 mucosal DC 的能力,到从另外的感染的房间的跨礼品的抗原的 DC 的能力,和开始 IgA 班在 B 房间切换的 mucosal DC 的能力的 plasmacytoid DC 的抗病毒的干扰素反应。DC 粘性在对 mucosal 病原体的有免疫力的反应也是批评的,当 DC 能对微型环境作出回应并且在附近的上皮的房间察觉到导致病原体的应力。最后, DC 通过串音与对方一起交往支持抗原表示和 T 房间免疫。一起,为对病原体的定制的有免疫力的回答的正式就职的这些过程条件 mucosal DC。 | Adam C Soloff | 2010 | Cell Research2010，20，8： | 4 |
| 14 | A comprehensive characterization of pancreatic ductal carcinoma cell lines: towards the establishment of an in vitro research platform显示文摘 | Bence Sipos Simone M?ser Holger Kalthoff Virag T?r?k Matthias L?hr Günter Kl?ppel | 2003 | Virchows Archiv2003，，5： | 4 |
| 15 | Urinary nuclear magnetic resonance spectroscopy of a Bangladeshi cohort with hepatitis-B hepatocellular carcinoma: A biomarker corroboration study显示文摘AIM: To establish if a distinct urinary metabolic profile could be identified in Bangladeshi hepatitis-B hepatocellular carcinoma(HCC) patients compared to cirrhosis patients and controls. METHODS: Urine samples from 42 Bangladeshi patients with HCC(39 patients with hepatitis-B HCC), 47 with cirrhosis on a background of hepatitis B, 46 with chronic hepatitis B, and seven ethnically-matched healthy controls were analyzed using nuclear magnetic resonance(NMR) spectroscopy. A full dietary and medication history was recorded for each subject. The urinary NMR data were analyzed using principal component analysis(PCA) and orthogonal partial leastsquared discriminant analysis(OPLS-DA) techniques. Differences in relative signal levels of the most discriminatory metabolites identified by PCA and OPLSDA were compared between subject groups using an independent samples Kruskal-Wallis one-way analysis of variance(ANOVA) test with all pairwise multiple comparisons. Within the patient subgroups, the MannWhitney U test was used to compare metabolite levels depending on hepatitis B e-antigen(HBe Ag) status and treatment with anti-viral therapy. A BenjaminiHochberg adjustment was applied to acquire the level of significance for multiple testing, with a declared level of statistical significance of P < 0.05.RESULTS: There were significant differences in age(P < 0.001), weight(P < 0.001), and body mass index(P < 0.001) across the four clinical subgroups. Serum alanine aminotransferase(ALT) was significantly higher in the HCC group compared to controls(P < 0.001); serum α-fetoprotein was generally markedly elevated in HCC compared to controls; and serum creatinine levels were significantly reduced in the HCC group compared to the cirrhosis group(P = 0.004). A threefactor PCA scores plot showed clustering of the urinary NMR spectra from the four subgroups. Metabolites that contributed to the discrimination between the subgroups included acetate, creatine, creatinine, dimethyamine(DMA), formate, glycine, hippurate, and trimethylamine-N-oxide(TMAO). A comparison of relative metabolite levels confirmed that carnitine was significantly increased in HCC; and creatinine, hippurate, and TMAO were significantly reduced in HCC compared to the other subgroups. HBe Ag negative patients showed a significant increase in creatinine(P = 0.001) compared to HBe Ag positive patients in the chronic hepatitis B subgroup, whilst HBe Ag negative patients showed a significant decrease in DMA(P = 0.004) in the cirrhosis subgroup compared to HBe Ag positive patients. There were no differences in metabolite levels in HCC patients who did or did not receive antiviral treatment. CONCLUSION: Urinary NMR changes in Bangladeshi HCC were identified, corroborating previous findings from Egypt and West Africa. These findings could form the basis for the development of a cost-effective HCC dipstick screening test. | I Jane Cox Abil E Aliev Mary ME Crossey Mahvish Dawood Mamun Al-Mahtab Sheikh M Akbar Salimur Rahman Antonio Riva Roger Williams Simon D Taylor-Robinson | 2016 | World Journal of Gastroenterology2016，22，16： | 4 |
| 16 | 《本族语者和非本族语者英语会话中的话语标记语》述评显示文摘 | Simone Müller 黄勤 罗选民 | 2008 | 外语教学与研究2008，40，5： | 4 |
| 17 | Role of interleukin-1 and its antagonism of hepatic stellate cell proliferation and liver fibrosis in the Abcb4^(-/-) mouse model显示文摘AIM: To study the interleukin-1(IL-1) pathway as a therapeutic target for liver fibrosis in vitro and in vivo using the ATP-binding cassette transporter b4^(-/-)(Abcb4^(-/-)) mouse model.METHODS: Female and male Abcb4^(-/-) mice from 6 to 13 mo of age were analysed for the degree of cholestasis(liver serum tests), extent of liver fibrosis(hydroxyproline content and Sirius red staining) and tissue-specific activation of signalling pathways such as the IL-1 pathway [quantitative polymerase chain reaction(q PCR)]. For in vivo experiments, murine hepatic stellate cells(HSCs) were isolated via pronasecollagenase perfusion followed by density gradient centrifugation using female mice. Murine HSCs were stimulated with up to 1 ng/m L IL-1β with or without 2.5 μg/m L Anakinra, an IL-1 receptor antagonist, respectively. The proliferation of murine HSCs was assessed via the Brd U assay. The toxicity of Anakinra was evaluated via the fluorescein diacetate hydrolysis(FDH) assay. In vivo 8-wk-old Abcb4^(-/-) mice with an already fully established hepatic phenotype were treated with Anakinra(1 mg/kg body-weight daily intraperitoneally) or vehicle and liver injury and liver fibrosis were evaluated via serum tests, q PCR, hydroxyproline content and Sirius red staining. RESULTS: Liver fibrosis was less pronounced in males than in female Abcb4^(-/-) animals as defined by a lower hydroxyproline content(274 ± 64 μg/g vs 436 ± 80 μg/g liver, respectively; n = 13-15; P < 0.001; MannWhitney U-test) and lower m RNA expression of the profibrogenic tissue inhibitor of metalloproteinase-1(TIMP)(1 ± 0.41 vs 0.66 ± 0.33 fold, respectively; n = 13-15; P < 0.05; Mann-Whitney U-test). Reduced liver fibrosis was associated with significantly lower levels of F4/80 m RNA expression(1 ± 0.28 vs 0.71 ± 0.41 fold, respectively; n = 12-15; P < 0.05; Mann-Whitney U-test) and significantly lower IL-1β m RNA expression levels(1 ± 0.38 vs 0.44 ± 0.26 fold, respectively; n = 13-15; P < 0.001; Mann-Whitney U-test). No gender differences in the serum liver parameters [bilirubin; alanine aminotransferase(ALT); aspartate aminotransferase and alkaline phosphatase(AP)] were found. In vitro, the administration of IL-1β resulted in a significant increase in HSC proliferation [0.94 ± 0.72 arbitrary units(A.U.) in untreated controls, 1.12 ± 0.80 A.U. at an IL-1β concentration of 0.1 ng/m L and 1.18 ± 0.73 A.U. at an IL-1β concentration of 1 ng/m L in samples from n = 6 donor animals; P < 0.001; analyses of variance(ANOVA)]. Proliferation was reduced significantly by the addition of 2.5 μg/m L Anakinra(0.81 ± 0.60 A.U. in untreated controls, 0.92 ± 0.68 A.U. at an IL-1β concentration of 0.1 ng/m L, and 0.91 ± 0.69 A.U. at an IL-1β concentration of 1 ng/m L; in samples from n = 6 donor animals; P < 0.001; ANOVA) suggesting an anti-proliferative effect of this clinically approved IL-1 receptor antagonist. The FDH assay showed this dose to be non-toxic in HSCs. In vivo, Anakinra had no effect on the hepatic hydroxyprolinecontent, liver serum tests(ALT and AP) and profibrotic(collagen 1α1, collagen 1α2, transforming growth factor-β, and TIMP-1) and anti-fibrotic [matrix metalloproteinase 2(MMP2), MMP9 and MMP13 ] gene expression after 4 wk of treatment. Furthermore, the hepatic IL-1β and F4/80 m RNA expression levels were unaffected by Anakinra treatment.CONCLUSION: IL-1β expression is associated with the degree of liver fibrosis in Abcb4^(-/-) mice and promotes HSC proliferation. IL-1 antagonism shows antifibrotic effects in vitro but not in Abcb4^(-/-) mice. | Florian P Reiter Ralf Wimmer Lena Wottke Renate Artmann Jutta M Nagel Manuel O Carranza Doris Mayr Christian Rust Peter Fickert Michael Trauner Alexander L Gerbes Simon Hohenester Gerald U Denk | 2016 | World Journal of Hepatology2016，8，8： | 3 |
| 18 | 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 |
| 19 | 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 |
| 20 | HBsAg quantification for identification of liver disease in chronic hepatitis B virus carriers显示文摘 | Simon B. Larsson Anders Eilard Sebastian Malmstr?m Charles Hannoun Amar P. Dhillon Gunnar Norkrans Magnus Lindh | 2014 | Liver Int2014，，7： | 3 |
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