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1Clinical epidemiology and disease burden of nonalcoholic fatty liver disease显示文摘Nonalcoholic fatty liver disease(NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis(NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma(HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type Ⅱ diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear toexperience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.Brandon J Perumpail Muhammad Ali Khan Eric R Yoo George Cholankeril Donghee Kim Aijaz Ahmed 2017World Journal of Gastroenterology2017,23,47:70
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
3Portal vein thrombosis, mortality and hepatic decompensation in patients with cirrhosis: A meta-analysis显示文摘AIM: To determine the clinical impact of portal vein thrombosis in terms of both mortality and hepatic decompensations(variceal hemorrhage, ascites, portosystemic encephalopathy) in adult patients with cirrhosis.METHODS: We identified original articles reported through February 2015 in MEDLINE, Scopus, Science Citation Index, AMED, the Cochrane Library, and relevant examples available in the grey literature. Two independent reviewers screened all citations for inclusion criteria and extracted summary data. Random effects odds ratios were calculated to obtain aggregate estimates of effect size across included studies, with 95%CI.RESULTS: A total of 226 citations were identified and reviewed, and 3 studies with 2436 participants were included in the meta-analysis of summary effect. Patients with portal vein thrombosis had an increased risk of mortality(OR = 1.62, 95%CI: 1.11-2.36, P = 0.01). Portal vein thrombosis was associated with an increased risk of ascites(OR = 2.52, 95%CI: 1.63-3.89, P < 0.001). There was insufficient data available to determine the pooled effect on other markers of decompensation including gastroesophageal variceal bleeding or hepatic encephalopathy. CONCLUSION: Portal vein thrombosis appears to increase mortality and ascites, however, the relatively small number of included studies limits more generalizable conclusions. More trials with a direct comparison group are needed.Jonathan G Stine Puja M Shah Scott L Cornella Sean R Rudnick Marwan S Ghabril George J Stukenborg Patrick G Northup 2015World Journal of Hepatology2015,7,27:42
4Cross-kingdom inhibition of breast cancer growth by plant miR159显示文摘MicroRNAs (miRNAs ) 是基因表示的批评管理者,并且在优核质的开发,生理学,和疾病施加广泛的影响。并行的高度在植物和动物在 miRNA 生物的续生说和行动的分子的基础被发现。最近的研究有趣地建议导出植物的 miRNAs 的一个潜在的跨王国的行动,通过饮食的吸入,在调整哺乳动物的基因表示。尽管在哺乳动物的标本检测的植物 miRNAs 的来源和范围仍然保持争论,这些起始的研究鼓舞了我们决定植物 miRNAs 是否能在西方的人的 sera 被检测并且这些植物 miRNAs 是否能影响与象癌症那样的人的疾病有关的基因表示和细胞的过程。这里,我们发现西方的施主 sera 包含了植物 miRNA miR159,其在浆液的丰富相反地在病人与乳癌发生和前进被相关。在人的 sera, miR159 主要在细胞外的泡被检测,并且对在 3 ′ 上建议发源植物的 2'-O-methylation 的钠 periodate 氧化抵抗;终端核糖。在乳癌房间然而并非非癌的乳房的上皮的房间,一合成 miR159 模仿能够由指向编码表明抄写因素的 Wnt 的 TCF7 禁止增长,在 MYC 蛋白质层次导致减少。miR159 的口头的管理显著地模仿在老鼠压制了异种皮移植胸肿瘤的生长。这些结果第一次证明植物 miRNA 能在哺乳动物禁止癌症生长。Andrew R Chin Miranda Y Fong George Somlo Jun Wu Piotr Swiderski Xiwei Wu Shizhen Emily Wang 2016Cell Research2016,26,2:35
5Bone mineral density and disorders of mineral metabolism in chronic liver disease显示文摘AIM:To estimate the prevalence and identify the risk factors for metabolic bone disease in patients with cirrhosis.METHODS:The study was performed on 72 Indian patients with cirrhosis(63 male, 9 female;aged < 50 years).Etiology of cirrhosis was alcoholism(n = 37), hepatitis B(n = 25) and hepatitis C(n = 10).Twenty-three patients belonged to Child class A, while 39 were in class B and 10 in class C.Secondary causes for metabolic bone disease and osteoporosis were ruled out.Sunlight exposure, physical activity and dietary constituents were calculated.Complete metabolic profiles were derived, and bone mineral density(BMD) was measured using dual energy X ray absorptiometry.Low BMD was defined as a Z score below-2.RESULTS:Low BMD was found in 68% of patients.Lumbar spine was the most frequently and severely affected site.Risk factors for low BMD included low physical activity, decreased sunlight exposure, and low lean body mass.Calcium intake was adequate, with unfavorable calcium:protein ratio and calcium:phosphorus ratio.Vitamin D deficiency was highly prevalent(92%).There was a high incidence of hypogonadism(41%).Serum estradiol level was elevated significantly in patients with normal BMD.Insulin-like growth factor(IGF) 1 and IGF binding protein 3 levels were below the age-related normal range in both groups.IGF-1 was signiflcantly lower in patients with low BMD.Serum osteocalcin level was low(68%) and urinary deoxypyridinoline to creatinine ratio was high(79%), which demonstrated low bone formation with high resorption.CONCLUSION:Patients with cirrhosis have low BMD.Contributory factors are reduced physical activity, low lean body mass, vitamin D def iciency and hypogonadism and low IGF-1 level.Joe George Hosahithlu K Ganesh Shrikrishna Acharya Tushar R Bandgar Vyankatesh Shivane Anjana Karvat Shobna J Bhatia Samir Shah Padmavathy S Menon Nalini Shah 2009World Journal of Gastroenterology2009,15,28:15
6Roles of unphosphorylated STATs in signaling显示文摘信号变换器的七个成员和抄写(STAT ) 的使活跃之物抄写因素的家庭被特定的酷氨酸残余的磷酸化响应许多不同 cytokines 和生长因素激活。STAT1 和 STAT3 基因是激活的 STAT 的特定的目标 1 和 3 分别地,响应干扰素(STAT1 ) 或 ligands 导致这些 unphosphorylated STAT (U-STATs ) 的层次的大增加那活跃 gp130,例如 IL-6 (STAT3 ) 。由从那些不同的新奇机制的 U-STATs 开车基因表示由 phosphorylated STAT (P-STAT ) 使用了暗淡 ers。在这评论,我们在基因表示的抄写和规定讨论 U-STATs 的角色。Jinbo Yang George R Stark 2008Cell Research2008,18,4:12
7Endoscopic mucosal resection of colorectal polyps in typical UK hospitals显示文摘AIM:To evaluate the outcomes of endoscopic mucosal resection(EMR) for colorectal polyps,with particular regard to procedural complications and recurrence rate,in typical United Kingdom(UK) hospitals that perform an average of about 25 colonic EMRs per year.METHODS:A total of 239 colorectal polyps(≥ 10 mm) resected from 199 patients referred to Rochdale Infirmary,Salford Royal Hospital and Royal Oldham Hospital for EMR between January 2003 and January 2009 were studied.RESULTS:The mean size of polyps resected was 19.6 ± 12.4 mm(range 10-80 mm).The overall major complication rate was 2.1%.Complications were less frequent with non-adenomas compared with the other groups(Pearson's χ 2 test,P < 0.0001).Resections of largersized polyps were more likely to result in complications(unpaired t-test,P = 0.021).Recurrence was associated with histology,with carcinoma-in-situ more likely to recur compared with low-grade dysplasia [hazard ratio(HR) 186.7,95% confidence interval(95% CI):8.81-3953.02,P = 0.001].Distal lesions were also more likely to recur compared with right-sided and transverse colon lesions(HR 5.93,95% CI:1.35-26.18,P = 0.019).CONCLUSION:EMR for colorectal polyps can be performed safely and effectively in typical UK hospitals.Stricter follow-up is required for histologically advanced lesions due to increased recurrence risk.Teegan R Lim Venkat Mahesh Salil Singh Benjamin HL Tan Mohamed Elsadig Nerukav Radhakrishnan Phil Conlong Chris Babbs Regi George 2010World Journal of Gastroenterology2010,16,42:11
8Role of functional imaging in the development and refinement of invasive neuromodulation for psychiatric disorders显示文摘Deep brain stimulation(DBS) is emerging as a pow-erful tool for the alleviation of targeted symptoms in treatment-resistant neuropsychiatric disorders. Despite the expanding use of neuropsychiatric DBS, the mecha-nisms responsible for its effects are only starting to be elucidated. Several modalities such as quantitative elec-troencephalography as well a intraoperative recordings have been utilized to attempt to understand the under-pinnings of this new treatment modality, but functional imaging appears to offer several unique advantages. Functional imaging techniques like positron emission tomography, single photon emission computed tomog-raphy and functional magnetic resonance imaging have been used to examine the effects of focal DBS on activ-ity in a distributed neural network. These investigations are critical for advancing the field of invasive neuro-modulation in a safe and effective manner, particularly in terms of defining the neuroanatomical targets and refining the stimulation protocols. The purpose of this review is to summarize the current functional neuroim-aging findings from neuropsychiatric DBS implantation for three disorders: treatment-resistant depression, obsessive-compulsive disorder, and Tourette syndrome. All of the major targets will be discussed(Nucleus ac-cumbens, anterior limb of internal capsule, subcallosal cingulate, Subthalamic nucleus, Centromedial nucleus of the thalamus-Parafasicular complex, frontal pole, and dorsolateral prefrontal cortex). We will also address some apparent inconsistencies within this literature, and suggest potential future directions for this promis-ing area.Nolan R Williams Joseph J Taylor Kayla Lamb Colleen A Hanlon E Baron Short Mark S George 2014World Journal of Radiology2014,6,10:6
9Nonlinear terahertz devices utilizing semiconducting plasmonic metamaterials显示文摘The development of responsive metamaterials has enabled the realization of compact tunable photonic devices capable of manipulating the amplitude,polarization,wave vector and frequency of light.Integration of semiconductors into the active regions of metallic resonators is a proven approach for creating nonlinear metamaterials through optoelectronic control of the semiconductor carrier density.Metal-free subwavelength resonant semiconductor structures offer an alternative approach to create dynamic metamaterials.We present InAs plasmonic disk arrays as a viable resonant metamaterial at terahertz frequencies.Importantly,InAs plasmonic disks exhibit a strong nonlinear response arising from electric field-induced intervalley scattering,resulting in a reduced carrier mobility thereby damping the plasmonic response.We demonstrate nonlinear perfect absorbers configured as either optical limiters or saturable absorbers,including flexible nonlinear absorbers achieved by transferring the disks to polyimide films.Nonlinear plasmonic metamaterials show potential for use in ultrafast terahertz(THz)optics and for passive protection of sensitive electromagnetic devices.Huseyin R Seren Jingdi Zhang George R Keiser Scott J Maddox Xiaoguang Zhao Kebin Fan Seth R Bank Xin Zhang Richard D Averitt 2016Light(Science & Applications)2016,5,1:4
10Brain changes in diabetes mellitus patients withgastrointestinal symptoms显示文摘Diabetes mellitus is a common disease and its prevalence is increasing worldwide. In various studies up to 30%-70% of patients present dysfunction and complications related to the gut. To date several clinical studies have demonstrated that autonomic nervous system neuropathy and generalized neuropathy of the central nervous system(CNS) may play a major role. This systematic review provides an overview of the neurodegenerative changes that occur as a consequence of diabetes with a focus on the CNS changes and gastrointestinal(GI) dysfunction. Animal models where diabetes was induced experimentally support that the disease induces changes in CNS. Recent investigations with electroencephalography and functional brain imaging in patients with diabetes confirm these structural and functional brain changes. Encephalographic studies demonstrated that altered insular processing of sensory stimuli seems to be a key player in symptom generation. In fact one study indicated that the more GI symptoms the patients experienced, the deeper the insular electrical source was located. The electroencephalography was often used in combination with quantitative sensory testingmainly showing hyposensitivity to stimulation of GI organs. Imaging studies on patients with diabetes and GI symptoms mainly showed microstructural changes,especially in brain areas involved in visceral sensory processing. As the electrophysiological and imaging changes were associated with GI and autonomic symptoms they may represent a future therapeutic target for treating diabetics either pharmacologically or with neuromodulation.Anne M Drewes Eirik Søfteland Georg Dimcevski Adam D Farmer Christina Brock Jens B Frøkjær Klaus Krogh Asbjørn M Drewes 2016World Journal of Diabetes2016,7,2:4
11Considerations for bariatric surgery in patients with cirrhosis显示文摘With the ever increasing global obesity pandemic, clinical burden from obesity related complications are anticipated in parallel. Bariatric surgery, a treatment approved for weight loss in morbidly obese patients, has reported to be associated with good outcomes, such as reversal of type two diabetes mellitus and reducing all-cause mortality on a long term basis. However, complications from bariatric surgery have similarly been reported. In particular, with the onslaught of non-alcoholic fatty liver disease(NAFLD) epidemic, in associated with obesity and metabolic syndrome, there is increasing prevalence of NAFLD related liver cirrhosis, which potentially connotes more risk of specific complications for surgery. Bariatric surgeons may encounter, either expectedly or unexpectedly, patients with non-alcoholic steatohepatitis(NASH) and NASH related cirrhosis more frequently. As such, the issues and considerations surrounding their medical care/surgery warrant careful deliberation to ensure the best outcomes. These considerations include severity of cirrhosis, liver synthetic function, portal hypertension and the impact of surgical factors. This review explores these considerations comprehensively and emphasizes the best approach to managing cirrhotic patients in the context of bariatric surgery.George Boon-Bee Goh Philip R Schauer Arthur J McCullough 2018World Journal of Gastroenterology2018,24,28:4
12Lysine methylation of promoter-bound transcription factors and relevance to cancer显示文摘p53, NF 魏 B, STAT3,和几个另外的抄写因素是 reversibly 由也修改 histones 的酶的离氨酸残余上的 methylated。NF 魏 B 和 STAT3 的 methylations 当他们倡导者一定时,发生,建议到 DNA 的可诱导的抄写因素的绑定在帮助到成员染色质修正机械的一个更一般的模型,它然后可以修改不仅 histones 而且界限抄写因素。某 histone 离氨酸 methyltransferases 和 demethylases 的变化被连接到癌症,并且这些变化可以改变不仅 histones 而且抄写因素的 methylation,并且可以因此是通过超过一机制的 tumorigenic。George R Stark Yuxin Wang Tao Lu 2011Cell Research2011,21,3:3
13Relative quantification of phosphoproteomic changes in grapevine (Vitis vinifera L.) leaves in response to abscisic acid显示文摘In a previous transcriptomic analysis,abscisic acid(ABA)was found to affect the abundance of a number of transcripts in leaves of Cabernet Sauvignon grapevines with roots that had been exposed to 10μM ABA for 2 h.Other work has indicated that ABA affects protein abundance and protein phosphorylation as well.In this study we investigated changes in protein abundance and phosphorylation of Cabernet Sauvignon grapevine leaves.Protein abundance was assessed by both label-free and isobaric-label quantitive proteomic methods.Each identified common proteins,but also additional proteins not found with the other method.Overall,several thousand proteins were identified and several hundred were quantified.In addition,hundreds of phosphoproteins were identified.Tens of proteins were found to be affected in the leaf after the roots had been exposed to ABA for 2 h,more than half of them were phosphorylated proteins.Many phosphosites were confirmed and several new ones were identified.ABA increased the abundance of some proteins,but the majority of the proteins had their protein abundance decreased.Many of these proteins were involved in growth and plant organ development,including proteins involved in protein synthesis,photosynthesis,sugar and amino-acid metabolism.This study provides new insights into how ABA regulates plant responses and acclimation to water deficits.Supakan Rattanakan Iniga George Paul A Haynes Grant R Cramer 2016Horticulture Research2016,3,1:3
14Safety, tolerability, and antibody response of active Aβ immunotherapy with CAD106 in patients with Alzheimer’s disease: randomised, double-blind, placebo-controlled, first-in-human study显示文摘Bengt Winblad Niels Andreasen Lennart Minthon Annette Floesser Georges Imbert Thomas Dumortier R Paul Maguire Kaj Blennow Joens Lundmark Matthias Staufenbiel Jean-Marc Orgogozo Ana Graf 2012Lancet Neurology2012,,7:3
15Noninvasive detection and evaluation of atherosclerotic coronary plaques with multislice computed tomography 1 1 This study was performed without additional financial support.显示文摘Stephen Schroeder Andreas F Kopp Andreas Baumbach Christoph Meisner Axel Kuettner Christian Georg Bernd Ohnesorge Christian Herdeg Claus D Claussen Karl R Karsch 2001Journal of the American College of Cardiology2001,,5:3
16建立初级卒中中心的修订和更新意见来自脑卒中联盟的总结声明显示文摘背景和目的自从2000年脑卒中联盟发布首份关于建立初级卒中中心的推荐意见以来,初级卒中中心的组建和认证工作已出现迅速发展。本文的目的在于修订和更新我们关于初级卒中中心的推荐意见以反映最新资料和经验。方法我们使用MEDLINE和PubMed数据库回顾了相关文献(2000年3月至2011年1月),主要针对急性卒中的诊断、治疗和护理。如果发现有效且相关,同样对原始文献、汇总分析和其他治疗指南进行回顾并纳入分析。标明证据等级以反映当前指南发展的实际情况。结果基于文献回顾以及针对初级卒中中心的经验,一些要素的重要性已得到进一步的加强,同时增加了几个新的领域。这些内容包括:(1)急诊卒中团队的重要性;(2)配备遥测监控的卒中单元的重要性;(3)MRj和弥散加权序列进行脑成像的实施;(4)用磁共振血管成像或CT血管成像对脑血管系统进行评价;(5)心脏影像学检查;(6)康复治疗的早期启动;(7)由独立机构进行的认证,包括实地考察和疾病评价指标。结论基于上述证据,初级卒中中心的某些要素对于改善急性卒中患者的诊治特别重要。其他要素则集中于脑、脑血管系统和心脏的影像学检查。这些新的要素也许能改善在初级卒中中心接受诊治的卒中患者的治疗和转归。Mark J. Alberts Richard E. Latchaw Andy Jagoda Lawrence R Wechsler Todd Crocco Mary G. George E.S. Connolly Barbara Mancini Stephen Prudhomme Daryl Gress Mary E. Jensen Robert Bass Robert Ruff Kathy Foell Rocco A. Armonda Marian Emr Margo Warren Jim Baranski Michael D. Walker 黄志超(译) 张霞(译) 尤寿江(译) 曹勇军(译) 刘春风(译) 2012国际脑血管病杂志2012,20,7:3
17德国弗莱维赫(德系西门塔尔)最佳乳肉兼用品种显示文摘在第四届中国国际奶业展览会及高层论坛上,韩国、日本、德国、荷兰奶业交流专场吸引了众多中外奶业界同仁。国外专家关于本国奶牛养殖业、乳品加工业的精彩报告,使与会代表对各国的奶业发展现状和趋势有了全面而深入地了解。本刊编辑部,对各位国外专家的发言进行了整理,现分韩国篇、日本篇、德国篇、荷兰篇四个部分予以刊登,以飨读者,希望对中国建设现代奶业有所借鉴。Georg R■hrmoser 2006中国乳业2006,,10:3
18Endostatin: An Endogenous Inhibitor of Angiogenesis and Tumor Growth显示文摘Michael S O’Reilly Thomas Boehm Yuen Shing Naomi Fukai George Vasios William S Lane Evelyn Flynn James R Birkhead Bjorn R Olsen Judah Folkman 1997Cell1997,,2:3
19Correlation between rpoB gene mutation in Mycobacterium avium subspecies paratuberculosis and clinical rifabutin and rifampicin resistance for treatment of Crohn’s disease显示文摘AIM: To investigate overlapping regions of the rpoB gene previously involved with rifamycin resistance in M. tuberculosis and seek correlation between rpoB mutations in clinical MAP strains with susceptibility to RIF and RFB. METHODS: We designed a molecular-based PCR method for the evaluation of rifabutin (RFB) and rifampicin (RIF) resistance based on probable determinant regions within the rpoB gene of MAP, including the 81 bp variable site located between nucleotides 1363 and 1443. The minimum inhibitory concentration (MIC) for RIF was also determined against 11 MAP isolates in attempt to seek correlation with rpoB sequences. RESULTS: We determined that MAP strain 18 had an MIC of > 30 mg/L and ≤ 5 mg/L for RIF and RFB respectively, and a significant and novel rpoB mutation C1367T, compared to an MIC of ≤ 1.0 mg/L for both drugs in the wild type MAP. The 30-fold increase in the MIC was a direct result of the rpoB mutation C1367T, which caused an amino acid change Thr456 to Ile456 in the drug’s binding site. In addition, MAP strain 185 contained five silent rpoB mutations and exhibited an MIC comparable to the wild-type. Moreover, our in vitroselected mutation in MAP strain UCF5 resulted in the generation of a new resistant strain (UCF5-RIF16r) that possessed T1442C rpoB mutation and an MIC > 30 mg/L and > 10 mg/L for RIF and RFB respectively. Sequencing of the entire rpoB gene in MAP strains UCF4, 18, and UCF5-RIF16r revealed an rpoB mutation A2284C further downstream of the 81 bp variable region in UCF4, accounting for observed slight increase in MIC. In addition, no other significant mutations were found in strains 18 and UCF-RIF16r. CONCLUSION: The data clearly illustrates that clinical and in vitro-selected MAP mutants with rpoB mutations result in resistance to RIF and RFB, and that a single amino acid change in the beta subunit may have a significant impact on RIF resistance. Unconventional drug susceptibility testing such as our molecular approach will be beneficial for evaluation of antibiotic effectiveness. This molecular approach may also serve as a model for other drugs used for treatment of MAP infections.Daniel R Beckler Sammer Elwasila George Ghobrial John F Valentine Saleh A Naser 2008World Journal of Gastroenterology2008,14,17:2
20Point-of-care testing in the diagnosis of gastrointestinal cancers: Current technology and future directions显示文摘Point-of-care(POC) tests enable rapid results and are well established in medical practice.Recent advances in analytical techniques have led to a new generation of POC devices that will alter gastrointestinal diagnostic pathways.This review aims to identify current and newtechnologies for the POC diagnosis of gastrointestinal cancer.A structured search of the Embase and Medline databases was performed.Papers reporting diagnostic tests for gastrointestinal cancer available as a POC device or containing a description of feasibility for POC application were included.Studies recovered were heterogeneous and therefore results are presented as a narrative review.Six diagnostic methods were identified(fecal occult blood, fecal proteins, volatile organic compounds, pyruvate kinase isoenzyme type M2, tumour markers and DNA analysis).Fecal occult blood testing has a reported sensitivity of 66%-85% and specificity greater than 95%.The others are at a range of development and clinical application.POC devices have a proven role in the diagnosis of gastrointestinal cancer.Barriers to their implementation exist and the transition from experimental to clinical medicine is currently slow.New technologies demonstrate potential to provide accurate POC tests and an ability to diagnose gastrointestinal cancer at an early stage with improved clinical outcome and survival.Jeremy R Huddy Melody Z Ni Sheraz R Markar George B Hanna 2015World Journal of Gastroenterology2015,21,14:2
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