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1Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease显示文摘Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of liver-related morbidity and mortality. It can develop secondary to numerous causes but a great majority of NAFLD cases occur in patients who are obese or present with other components of metabolic syndrome (hypertension, dyslipidemia, diabetes). This is called primary NAFLD and insulin resistance plays a key role in its pathogenesis. Obesity is characterized by expanded adipose tissue, which is under a state of chronic inflammation. This disturbs the normal storage and endocrine functions of adipose tissue. In obesity, the secretome (adipokines, cytokines, free fatty acids and other lipid moieties) of fatty tissue is amplified, which through its autocrine, paracrine actions in fat tissue and systemic effects especially in the liver leads to an altered metabolic state with insulin resistance (IR). IR leads to hyperglycemia and reactive hyperinsulinemia, which stimulates lipid-accumulating processes and impairs hepatic lipid metabolism. IR enhances free fatty acid delivery to liver from the adipose tissue storage due to uninhibited lipolysis. These changes result in hepatic abnormal fat accumulation, which may initiate the hepatic IR and further aggravate the altered metabolic state of whole body. Hepatic steatosis can also be explained by the fact that there is enhanced dietary fat delivery and physical inactivity. IR and NAFLD are also seen in various lipodystrophic states in contrary to popular belief that these problems only occur due to excessive adiposity in obesity. Hence, altered physiology of adipose tissue is central to development of IR, metabolic syndrome and NAFLD.Kamran Qureshi Gary A Abrams 2007World Journal of Gastroenterology2007,13,26:52
2Hypoxia-regulated microRNAs in human cancer显示文摘Guomin SHEN Xiaobo LI Yong-feng JIA Gary A PIAZZA Yaguang XI 2013Acta Pharmacologica Sinica2013,34,3:18
3皮质下小血管病诊断的共识声明显示文摘血管性认知损害是用于描述一组涉及大血管和小血管的散发性和遗传性异质性疾病的诊断术语。皮质下小血管病可导致腔隙性梗死和进行性白质损害。被称为宾斯旺格病(Binswanger's disease, BD)的进行性白质损害患者构成了从单纯血管性疾病到合并神经变性病变的疾病谱。BD患者是一个相对同质性的亚组,存在缺氧缺血、腔隙性梗死和炎症,它们协同作用破坏血脑屏障和髓鞘。通过临床、脑脊液、神经心理学和影像学检查获得的多模式疾病标记物能促进该亚组患者的鉴别。本共识声明确定了一系列基于基础病理学改变的潜在生物学标记物,这将有助于诊断以及将来协作性治疗试验的患者选择。Gary A Rosenberg Anders Wallin Joanna M Wardlaw Hugh S Markus Joan Montaner Leslie Wolfson Costantino Iadecola Berislav V Zlokovic Anne Joutel Martin Dichgans Marco Duering Reinhold Schmidt Amos D Korczyn Lea T Grinberg Helena C Chui Vladimir Hachinski 王训师 张劼 陈涵丰 俞娅美 徐子奇 罗本燕 2016国际脑血管病杂志2016,24,6:18
4冠状动脉内影像学临床应用专家共识(第一部分):对冠状动脉介入治疗的指导与优化显示文摘欧洲心血管介入协会(EAPCI)专家组系统总结了血管内超声(IVUS)和光学相干断层成像(OCT)这两种血管内影像学检查临床应用指征的现有证据,提供了关于IVUS和OCT指导经皮冠状动脉介入治疗(PCI)的应用价值,并明确了最可能从腔内影像学指导的介入治疗中获得临床收益的患者或病变类型,同时详细论述了PCI前如何使用IVUS或OCT优化支架尺寸(支架长度和直径)和手术策略的选择。此外,专家推荐对支架失败(支架内再狭窄或支架内血栓形成)的患者应常规进行冠状动脉内影像学检查,并首选OCT。最后,重点论述了IVUS和OCT在指导PCI和评估支架失败两个方面的优势和局限性,并对未来需要深入研究的领域进行了展望。Lorenz Raber Gary S Mintz Konstantinos C Koskinas Thomas W Johnson Niels R Holm Yoshinubo Onuma Maria D Radu Michael Joner Bo Yu Haibo Jia Nicolas Meneveau Jose M.de la Torre Hemandez Javier Escaned Jonathan Hill Francesco Prati Antonio Colombo Carlo di Mario Evelyn Regar Davide Capodanno William Wijns Robert A Byme Giulio Guagliumi 2019中华心血管病杂志2019,47,1:17
5Nanofluid-based optical filter optimization for PV/T systems显示文摘Optical filters are essential in a wide range of applications,including optical communications,electronics,lighting,optical sensors and photography.This article presents recent work which indicates that optical filters can be created from specialized nanoparticle suspensions.Specifically,this article describes a theoretical optimization process for designing nanofluid-based filters for hybrid solar photovoltaic/thermal(PV/T)applications.This particular application is suitable because nanofluids can be utilized as both volumetric solar absorbers and flowing heat transfer mediums.The nanofluid filters described in this work compare favorably with conventional optical filters for five photovoltaic(PV)cell alternatives:InGaP,CdTe,InGaAs,Si,and Ge.This study demonstrates that nanofluids make efficient,compact and potentially low-cost,spectrally selective optical filters.Robert A Taylor Todd Otanicar Gary Rosengarten 2012Light(Science & Applications)2012,1,1:12
6Global secretome analysis identifies novel mediators of bone metastasis显示文摘骨头是稳固的肿瘤的远转移的一个最普通的地点。分泌蛋白质被知道影响在变形癌症房间和骨头基质之间的病理学的相互作用。为了包括地介绍,分泌了与骨头转移联系的蛋白质,我们使用了量、非量的集体 spectrometry 全球性分析改变从多重种类和癌症的变形能力打的骨头的九根细胞线的 secretomes。由比较父母房间和他们的骨头的 secretomes 变形衍生物,我们识别了特别地在这些房间线与骨头转移被联系的分泌蛋白质。我们然后合并了大临床的转移数据集的生物信息的分析获得强烈与临床、试验性的骨头转移被联系的几个功能的班的候选人小说骨头转移蛋白质的一张表。选择蛋白质的功能的确认显示在 vivo,骨头转移能被高表示支持(1 ) 唾液的 cystatins CST1, CST2,和 CST4;(2 ) plasminogen 使活跃之物小块地和 PLAU;或(3 ) 骨胶原功能蛋白质 PLOD2 和 COL6A1。总的来说,我们的学习揭开了骨头转移并且因此的几个新分泌调停人证明 secretome 分析是为新奇 biomarkers 和候选人的鉴定的一个强大的方法治疗学的目标。Maria Andres Blanco Gary LeRoy Zia Khan Ma a Ale kovi Barry M Zee Benjamin A Garcia Yibin Kang 2012Cell Research2012,22,9:12
7Preemptive mechanical ventilation can block progressive acute lung injury显示文摘Mortality from acute respiratory distress syndrome(ARDS) remains unacceptable, approaching 45% in certain high-risk patient populations. Treating fulminant ARDS is currently relegated to supportive care measures only. Thus, the best treatment for ARDS may lie with preventing this syndrome from ever occurring. Clinical studies were examined to determine why ARDS has remained resistant to treatment over the past several decades. In addition, both basic science and clinical studies were examined to determine the impact that early, protective mechanical ventilation may have on preventing the development of ARDS in at-risk patients. Fulminant ARDS is highly resistant to both pharmacologic treatment and methods of mechanical ventilation. However, ARDS is a progressive disease with an early treatment window that can be exploited. In particular, protective mechanical ventilation initiated before the onset of lung injury can prevent the progression to ARDS. Airway pressure release ventilation(APRV) is a novel mechanical ventilation strategy for delivering a protective breath that has been shown to block progressive acute lung injury(ALI) and prevent ALI from progressing to ARDS. ARDS mortality currently remains as high as 45% in some studies. As ARDS is a progressive disease, the key to treatment lies with preventing the disease from ever occurring while it remains subclinical. Early protective mechanical ventilation with APRV appears to offer substantial benefit in this regard and may be the prophylactic treatment of choice for preventing ARDS.Benjamin Sadowitz Sumeet Jain Michaela Kollisch-Singule Joshua Satalin Penny Andrews Nader Habashi Louis A Gatto Gary Nieman 2016World Journal of Critical Care Medicine2016,5,1:9
8The interaction between the Wnt/β-catenin signaling cascade and PKG activation in cancer显示文摘The activation of the Wnt/β-catenin signaling cascade has been well studied and documented in colorectal cancer(CRC).The long-term use of non-steroidal anti-inflammatory drugs(NSAIDs) has been shown to reduce the incidence and risk of death from CRC in numerous epidemiological studies.The NSA1 D sulindac has also been reported to cause regression of precancerous adenomas in individuals with familial adenomatous polyposis who are at high risk of developing CRC.The mechanism responsible for cancer chemopreventive activity of NSAIDs is not well understood but may be unrelated to their cyclooxygenase inhibitory activity.Emerging evidence suggests that sulindac inhibits the growth of colon tumor cells by suppressing the activity of certain phosphodiesterase isozymes to activate cGMβ-dependent protein kinase,PKG,through the elevation of the second messenger cyclic guanosine monophosphote,cGMP.PKG activation has been shown to inhibit the nuclear translocation of β-catenin,reduce β-catenin mRNA and protein levels,and suppress the transcriptional activity of β-catenin.This review describes the relationship between the Wnt/β-catenin signaling cascade and the activation of PKG through PDE inhibition and elevation of intracellular cGMP levels.Kevin Lee Gary A Piazza 2017The Journal of Biomedical Research2017,31,3:7
9Dynamic chromatin states in human ES cells reveal potential regulatory sequences and genes involved in pluripotency显示文摘Pluripotency,一个细胞的能力区分并且产生所有胚胎的系,定义象胚胎的茎(ES ) 那样的哺乳动物的细胞类型的一个小数字细胞。当它通常被保持了时,那 pluripotency 是 transcriptional 的产品激活并且维持关键干细胞基因的表达式的规章的网络,积累的证据在建立并且保卫 ES 房间的 pluripotency 为 epigenetic 进程正在指向一个关键角色,象维持区分的房间类型的身份一样。以便更好在 pluripotency 理解 epigenetic 机制的角色,我们检验了在经历区别进一个 mesendodermal 系的人的 ES 房间(hESCs ) 染色体宽的染色质修正的动力学。我们发现在倡导者的染色质修正在区别期间仍然保持大部分不变,除了在在在 H3K27 的 acetylation 和 methylation 之间的一个动态开关标记在基因表示的激活和 silencing 之间的转变的倡导者的一个小数字,建议在在大多数差别上的房间命运承诺的一个层次表示了基因。我们也在 50 000 潜在的 enhancers 上印射,并且在染色质修正,特别 H3K4me1 和 H3K27ac 观察了大得多的动力学,它与他们的潜在的目标基因的表示相关。这些 enhancers 的进一步的分析揭示了 pluripotency 和可以在 hESCs 授与发展胜任的一个平衡状态的一口染色质签名陈述语气的潜在地关键的 transcriptional 管理者。我们的结果提供在定义 enhancers 和 pluripotency 支持染色质修正的角色的新证据。R David Hawkins Gary C Hon Chuhu Yang Jessica E Antosiewicz-Bourget Leonard K Lee Que-Minh Ngo Sarit Klugman Keith A Ching Lee E Edsall Zhen Ye Samantha Kuan Pengzhi Yu Hui Liu Xinmin Zhang Roland D Green Victor V Lobanenkov Ron Stewart James A Thomson Bing Ren 2011Cell Research2011,21,10:6
10针对患者利益的机器学习和人工智能研究:在透明性、可重复性、伦理和有效性等方面的20个关键问题显示文摘机器学习(ML)、人工智能(AI)和其他现代统计方法正为利用先前尚未开发且极速增长的数据资源提供新的机会,以期让患者获益。尽管目前正在进行许多有前景的研究,特别是在图像方面,但就文献整体而言还缺乏透明度、对可重复性清晰的阐述、对潜在伦理问题的探究,以及对有效性的明确验证。这些问题的存在有许多原因,其中最重要的一点(为此我们提供了初步解决方案)就是当前缺乏针对ML和AI的最佳实践指南。我们认为从事研究的跨学科团队和应用ML/AI影响健康的项目,将因解决有关透明度、可重复性、伦理和有效性(TREE)的一系列问题而受益。这里提出的20个关键问题为研究团队提供了一个研究设计、实施和报告框架;帮助编辑和同行评审专家评估文献的贡献;让患者、临床医生和政策制定者评估新发现可能会给患者带来的获益。Sebastian Vollmer Bilal A Mateen Gergo Bohner Franz J Kirdly Rayid Ghani Pall Jonsson Sarah Cumbers Adrian Jonas Katherine S L McAllister Puja Myles David Granger Mark Birse Richard Branson Karel G M Moons Gary S Collins John P A Chris Holmes Harry Hemingwayp 李峰(译) 徐磊(校) 赵邑(校) 2020英国医学杂志中文版2020,23,9:5
11Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis显示文摘AIM: To evaluate the effect of orally administeredplecanatide or dolcanatide, analogs of uroguanylin, on amelioration of colitis in murine models.METHODS: The cyclic guanosine monophosphate(cG MP) stimulatory potency of plecanatide and dolcanatide was measured using a human colon carcinoma T84 cellbased assay. For animal studies all test agents were formulated in phosphate buffered saline. Sulfasalazine or 5-amino salicylic acid(5-ASA) served as positive controls. Effect of oral treatment with test agents on amelioration of acute colitis induced either by dextran sulfate sodium(DSS) in drinking water or by rectal instillation of trinitrobenzene sulfonic(TNBS) acid, was examined in BALB/c and/or BDF1 mice. Additionally, the effect of orally administered plecanatide on the spontaneous colitis in T-cell receptor alpha knockout(TCRα-/-) mice was also examined. Amelioration of colitis was assessed by monitoring severity of colitis, disease activity index and by histopathology. Frozen colon tissues were used to measure myeloperoxidase activity.RESULTS: Plecanatide and dolcanatide are structurally related analogs of uroguanylin, which is an endogenous ligand of guanylate cyclase-C(GC-C). As expected from the agonists of GC-C, both plecanatide and dolcanatide exhibited potent cG MP-stimulatory activity in T84 cells. Once-daily treatment by oral gavage with either of these analogs(0.05-0.5 mg/kg) ameliorated colitis in both DSS and TNBS-induced models of acute colitis, as assessed by body weight, reduction in colitis severity(P < 0.05) and disease activity index(P < 0.05). Amelioration of colitis by either of the drug candidates was comparable to that achieved by orally administered sulfasalazine or 5-ASA. Plecanatide also effectively ameliorated colitis in TCRα-/- mice, a model of spontaneous colitis. As dolcanatide exhibited higher resistance to proteolysis in simulated gastric and intestinal juices, it was selected for further studies. CONCLUSION: This is the first-ever study reporting the therapeutic utility of GC-C agonists as a new class of orally delivered and mucosally active drug candidates for the treatment of inflammatory bowel diseases.Kunwar Shailubhai Vaseem Palejwala Krishna Priya Arjunan Sayali Saykhedkar Bradley Nefsky John A Foss Stephen Comiskey Gary S Jacob Scott E Plevy 2015World Journal of Gastrointestinal Pharmacology and Therapeutics2015,6,4:5
12RNA binding proteins in spermatogenesis: an in depth focus on the Musashi family显示文摘控制基因规定为维持繁殖潜力在配偶子开发期间是重要的。在哺乳动物的精子发生的复杂过程期间,尽管有重翻译要求,男细菌房间为继续的生长和区别经历不活跃的抄写的扩大时期。因此,精子发生高度依赖基因表示的 posttranscriptional 规定的机制,由 RNA 有约束力的蛋白质(RBP ) 便于,它仍然保持富有地在整个这进程表示了。一如此的组蛋白质是 Musashi 家庭,以前在果蝇识别了睾丸细菌房间开发和成熟分裂的同样批评的管理者,并且也出现对在老鼠的精子开发和繁殖潜力重要。这评论在男细菌房间开发的范围以内描述 RBP 的角色和函数,集中于我们在精子发生的 Musashi 蛋白质的最近的知识。RBP 在房间以内利用的功能的机制在与模式的关系深入地亚 cellular 本地化和阶段特定的表示的,和意义被构画出, posttranscriptional 规定的影响也被加亮。当原来在果蝇和 Xenopus 描绘了,我们在干细胞功能和房间命运决心强调 RBP 的 Musashi 家庭的历史的角色,并且与我们微分角色的当前的理解和哺乳动物的 Musashi 蛋白质, Musashi-1 和 Musashi-2 的功能得出结论,与我们在精子发生的调查结果的一个主要焦点。这评论两个都作为男配偶子开发的主人管理者加亮 RBP 的必要贡献到 posttranscriptional 规定和 Musashi 家庭的重要性。Jessie M Sutherland Nicole A Siddall Gary R Hime Eileen A McLaughlin 2015Asian Journal of Andrology2015,17,4:4
13Access related complications during anterior exposure of the lumbar spine显示文摘The new millennium has witnessed the emergence of minimally invasive, non-posterior based surgery of the lumbar spine, in particular via lateral based methodologies to discectomy and fusion. In contrast, and perhaps for a variety of reasons, anterior motion preservation(non-fusion) technologies are playing a comparatively lesser, though incompletely defined, role at present. Lateral based motion preservation technologies await definition of their eventual role in the armamentarium of minimally invasive surgical therapies of the lumbar spine. While injury to the major vascular structures remains the most serious and feared complication of the anterior approach, this occurrence has been nearly eliminated by the use of lateral based approaches for discectomy and fusion cephalad to L5-S1. Whether anterior or lateral based, non-posterior approaches to the lumbar spine share certain access related pitfalls and complications, including damage to the urologic and neurologic structures, as well as gastrointestinal and abdominal wall issues. This review will focus on the recognition, management and prevention of these anterior and lateral access related complications.Gary A Fantini Abhijit Y Pawar 2013World Journal of Orthopedics2013,4,1:4
14Outcomes of Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding显示文摘AIM:To evaluate weight loss and surgical outcomes of Roux-en-Y gastric bypass(RYGB)and laparoscopic adjustable gastric band(LAGB).METHODS:Data relating to changes in body mass index(BMI)and procedural complications after RYGB(1995-2009;n=609;116M:493F;42.4±0.4 years)or LAGB(2004-2009;n=686;131M:555F;37.2±0.4years)were extracted from prospective databases.RESULTS:Pre-operative BMI was higher in RYGB than LAGB patients(46.8±7.1 kg/m2vs 40.4±4.2 kg/m2,P<001);more patients with BMI<35 kg/m2underwent LAGB than RYGB(17.1%vs 4.1%,P<0.0001).BMI decrease was greater after RYGB.There were direct relationships between weight loss and pre-operative BMI(P<0.001).Although there was no difference in weight loss between genders during the first 3-year post-surgery,male LAGB patients had greater BMI reduction than females(-8.2±4.3 kg/m2vs-3.9±1.9kg/m2,P=0.02).Peri-operative complications occurred more frequently following RYGB than LAGB(8.0%vs0.5%,P<0.001);majority related to wound infection.LAGB had more long-term complications requiring corrective procedures than RYGB(8.9%vs 2.1%,P<0.001).Conversion to RYGB resulted in greater BMI reduction(-9.5±3.8 kg/m2)compared to removal and replacement of the band(-6.0±3.0 kg/m2).Twelve months post-surgery,fasting glucose,total cholesterol and low density lipoprotein levels were significantly lower with the magnitude of reduction greater in RYGB patients.CONCLUSION:RYGB produces substantially greater weight loss than LAGB.Whilst peri-operative complications are greater after RYGB,long-term complication rate is higher following LAGB.Nam Q Nguyen Philip Game Justin Bessell Tamara L Debreceni Melissa Neo Carly M Burgstad Pennie Taylor Gary A Wittert 2013World Journal of Gastroenterology2013,19,36:3
15Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial显示文摘William T Cefalu Lawrence A Leiter Kun-Ho Yoon Pablo Arias Leo Niskanen John Xie Dainius A Balis William Canovatchel Gary Meininger 2013The Lancet2013,,:3
163T magnetic resonance neurography of pudendal nerve with cadaveric dissection correlation显示文摘AIM: To evaluate the pudendal nerve segments that could be identified on magnetic resonance neurography(MRN) before and after surgical marking of different nerve segments.METHODS: The hypothesis for this study was that pudendal nerve and its branches would be more easily seen after the surgical nerve marking. Institutional board approval was obtained. One male and one female cadaver pelvis were obtained from the anatomy board and were scanned using 3 Tesla MRI scanner using MR neurography sequences. All possible pudendal nerve branches were identified. The cadavers were then sent to the autopsy lab and were surgically dissected by a peripheral nerve surgeon and an anatomist to identify the pudendal nerve branches. Radiological markers were placed along the course of the pudendal nerve and its branches. The cadavers were then closed and rescanned using the same MRN protocol as the premarking scan. The remaining pudendal nerve branches were attempted to be identified using the radiological markers. All scans were read by an experienced musculoskeletal radiologist.RESULTS: The pre-marking MR Neurography scans clearly showed the pudendal nerve at its exit from the lumbosacral plexus in the sciatic notch, at the level of the ischial spine and in the Alcock's Canal in both cadavers. Additionally, the right hemorrhoidal branch could be identified in the male pelvis cadaver. The perineal and distal genital branches could not be identified. On post-marking scans, the markers were used as identifiable structures. The location of the perineal branch, the hemorroidal branch and the dorsal nerve to penis(in male cadaver)/clitoris(in female cadaver) could be seen. However, the visualization of these branches was suboptimal. The contralateral corresponding nerves were poorly seen despite marking on the surgical side. The nerve was best seen on axial T1W and T2W SPAIR images. The proximal segment could be seen well on 3D DW PSIF sequence. T2W SPACE was not very useful in visualization of this small nerve or its branches.CONCLUSION: Proximal pudendal nerve is easily seen on MR neurography, however it is not possible to identify distal branches of the pudendal nerve even after surgical marking.Avneesh Chhabra Courtney A McKenna Vibhor Wadhwa Gaurav K Thawait John A Carrino Gary P Lees A Lee Dellon 2016World Journal of Radiology2016,8,7:3
17MicroRNAs are involved in the self-renewal and differentiation of cancer stem cells显示文摘MicroRNAs (miRNAs ) 是小非编码的 RNA 分子,其主要功能是在 post-transcriptional/translational 调整基因表示,铺平。MiRNAs 玩在正常生物过程的关键角色并且在人的疾病是通常调整 dys 的。干细胞被认为是 “ mother”包括身体的纸巾和机关的区分的房间的所有类型的房间。一个新奇假设建议肿瘤由从癌症干细胞导出的异构的房间组成,它有正常干细胞的类似于那些的自强和区别能力。癌症干细胞从各种各样的肿瘤被孤立并且描绘。在癌症干细胞的自强和区别支持 miRNAs 的关键规章的角色的给定的最近的研究,更好理解 miRNAs 的功能将提供无价的卓见进 tumorigenesis 和肿瘤前进的预防。在这评论,我们将在涉及癌症干细胞的自强和区别的 miRNAs 的学习总结研究进步。Zheng-ming WANG Wen-jun DU Gary A PIAZZA Yaguang XI 2013Acta Pharmacologica Sinica2013,34,11:3
18Transanal total mesorectal excision:a valid option for rectal cancer?显示文摘Low anterior resection can be a challenging operation, especially in obese male patients and in particular after radiotherapy. Transanal total mesorectal excision(Ta TME) might offer technical advantages over laparoscopic or open approaches particularly for tumors in the distal third of the rectum. The aim of this article is to review the current experience with Ta TME. The limits and future developments are also explored. Although the experience with Ta TME is still limited, it might be a promising alternative to laparoscopic TME, especially for difficult cases where laparoscopy is too demanding. The preliminary data on complications and short-term oncological outcomes are good, but also emphasize the importance of careful patient selection. Finally, there is a need for large-scale trials focusing on long-term outcomes and oncological safety before widespread adoption can be recommended.Nicolas C Buchs Gary A Nicholson Frederic Ris Neil J Mortensen Roel Hompes 2015World Journal of Gastroenterology2015,21,41:3
19Stratification of outcomes for mucinous appendiceal adenocarcinoma with peritoneal metastasis by histological grade显示文摘AIM To investigate the importance of a three-tiered histologic grade on outcomes for patients with mucinous appendiceal adenocarcinoma(MAA).METHODS Two hundred and sixty-five patients with MAA undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were identified from a prospective database from 2004 through 2014. All pathology was reviewed by our gastrointestinal subspecialty pathologists and histological grade was classified as well-differentiated, moderately differentiated, and poorly differentiated. Survival analysis was performed using Cox proportional hazards regression.RESULTS There were 201(75.8%) well-, 45(16.9%) moderatelyand 19(7.2%) poorly-differentiated tumors. Histological grade significantly stratified the 5-year overall survival(OS), 94%, 71% and 30% respectively(P < 0.001) as well as the 5-year disease-free survival(DFS) 66%, 21% and 0%, respectively(P < 0.001). Independent predictors of DFS included tumor grade(HR = 1.78, 95%CI: 1.21-2.63, P = 0.008), lymph node involvement(HR = 0.33, 95%CI: 0.11-0.98, P < 0.02), previous surgical score(HR = 1.31, 95%CI: 1.1-1.65, P = 0.03) and peritoneal carcinomatosis index(PCI)(HR = 1.05, 95%CI: 1.02-1.08, P = 0.002). Independent predictors of OS include tumor grade(HR = 2.79, 95%CI: 1.26-6.21, P = 0.01), PCI(HR = 1.10, 95%CI: 1.03-1.16, P = 0.002), and complete cytoreduction(HR = 0.32, 95%CI: 0.11-0.92, P = 0.03). Tumor grade and PCI were the only independent predictors of both DFS and OS. Furthermore, histological grade and lymphovascular invasion stratified the risk of lymph node metastasis into a low(6%) and high(40%) risk groups. CONCLUSION Our data demonstrates that moderately differentiated MAA have a clinical behavior and outcome that is distinct from well-and poorly-differentiated MAA. The threetier grade classification provides improved prognostic stratification and should be incorporated into patient selection and treatment algorithms.Travis Edward Grotz Richard E Royal Paul F Mansfield Michael James Overman Gary N Mann Kristen Ashlee Robinson Karen A Beaty Safiea Rafeeq Auerlio Matamoros Michelle W Taggart Keith Francis Fournier 2017World Journal of Gastrointestinal Oncology2017,9,9:2
20Overexpression of fibrinogen-like protein 2 protects against T cell-induced colitis显示文摘AIM To determine the effect of overexpression of fibrinogenlike protein 2(FGL2) on regulatory T cell(Treg) and effector T(Teff) cell function on T cell-induced colitis in Rag1-/-mice.METHODS Treg and Teff cells from fgl2-/-, fgl2+/+, and fgl2 Tg mice were purified by FACS. They were studied in vitro for immunosuppressive activity and cell proliferation and in vivo for their effects on the development and prevention of T cell-induced colitis in Rag1-/-mice. RESULTS In vitro, fgl2 Tg Treg had enhanced immunosuppressive activity, and fgl2 Tg Teff had reduced proliferation to alloantigen stimulation. Transfer of Teff from C57Bl/6J mice(fgl2+/+) into Rag1-/-mice produced both clinical and histologic colitis with dense infiltrates of CD3+ T cells, crypt abscesses and loss of goblet cells. Fgl2 Tg Treg prevented the development of T cell-induced colitis, whereas fgl2+/+ and fgl2-/-Treg were only partially protective. In mice that received fgl2 Tg Treg, the ratio of Foxp3+ to CD3+ cells was increased both in the colon and in mesenteric lymph nodes, and Teff cell proliferation as determined by staining with Ki67 was reduced. Teff cells from fgl2 Tg mice did not produce colitis. CONCLUSION Here we show that fgl2 Tg Teff are hypoproliferative and do not induce colitis. We further demonstrate that fgl2 Tg Treg prevent colitis in contrast to fgl2+/+ Treg, which were only partially protective. These studies collectively provide a rationale for exploring the use of FGL2 or Treg expressing high levels of FGL2 in the treatment of inflammatory bowel disease.Agata Bartczak Jianhua Zhang Oyedele Adeyi Achiya Amir David Grant Reginald Gorczynski Nazia Selzner Andrzej Chruscinski Gary A Levy 2017World Journal of Gastroenterology2017,23,15:2
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