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| 1 | 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 |
| 2 | AGNP精神科治疗药物监测共识指南:2011显示文摘治疗药物监测(Therapeutic drug monitoring,TDM),如通过定量测定血清或血浆药物浓度指导用药剂量优化,已经成为对患者进行精神药物治疗的很有价值的工具。在患者用药依从性难以判断、药物耐受性不佳、治疗剂量下无效以及可能存在药代动力学药物-药物相互作用等情况下,测定药物浓度是很有用的。在精神科,有可能明显获益于TDM的主要患者群体包括儿童、孕妇、老年患者、智力障碍患者、涉及司法的患者、已知或怀疑携带药代动力学相关基因变异的患者,以及合并躯体疾病影响药代动力学的患者。然而,只有将TDM充分整合到临床治疗过程中去,才能发挥其优化药物治疗的潜在优势。为了促进TDM的合理应用,神经精神药理学与药物精神病学协会(Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie,AGNP)的TDM专家组在2004年发表了精神药物治疗药物监测指南。之后,随着知识不断更新,又有许多可能需要进行TDM的新药上市。因此,本次更新将神经精神药物的种类扩展到了128种,并将其TDM必要性划分为从'强烈推荐'到'可能有用'的四个等级。经过大量细致且全面的文献检索与分门别类的汇总整理,将基于循证医学理念的'治疗参考浓度范围'和'剂量相关参考浓度范围'呈现给大家。本共识指南引入了'实验室警戒浓度'的新概念,即实验室需要马上告知治疗医生的药物浓度上限。本共识指南还给出了诸如药物作为细胞色素P450酶的底物和抑制剂的性质,代谢物与母药浓度比值的常见范围,以及与结果解释相关的内容,还提供了何时将TDM与遗传药理学检测相结合的建议。遵循本指南,有助于改善许多患者精神药物治疗的效果,特别是那些存在药代动力学异常的患者。TDM是一门交叉学科,有时针对看起来不一致的数据,需要多学科坦诚地讨论,只有这样,患者才能从这种合作中获益。 | Hiemke C Baumann P Bergemann N Conca A Dietmaier O Egberts K Fric M Gerlach M Greiner C Gründer G Haen E Havemann-Reinecke U Jaquenoud Sirot E Kirchherr H Laux G Lutz UC Messer T Müller MJ Pfuhlmann B Rambeck B Riederer P Schoppek B Stingl J Uhr M Ulrich S Waschgler R Zernig G 李文标(译) 果伟(译) 阮灿军(译) 贺静(译) 汤宜朗(审校) 王传跃(审校) | 2016 | 实用药物与临床2016，19，10： | 37 |
| 3 | Impact of mechanical bowel preparation in elective colorectal surgery:A meta-analysis显示文摘AIM To analyse the effect of mechanical bowel preparation vs no mechanical bowel preparation on outcome in patients undergoing elective colorectal surgery.METHODS Meta-analysis of randomised controlled trials and observational studies comparing adult patients receiving mechanical bowel preparation with those receiving no mechanical bowel preparation, subdivided into those receiving a single rectal enema and those who received no preparation at all prior to elective colorectal surgery. RESULTS A total of 36 studies(23 randomised controlled trials and 13 observational studies) including 21568 patients undergoing elective colorectal surgery were included. When all studies were considered, mechanical bowel preparation was not associated with any significant difference in anastomotic leak rates(OR = 0.90, 95%CI: 0.74 to 1.10, P = 0.32), surgical site infection(OR = 0.99, 95%CI: 0.80 to 1.24, P = 0.96), intraabdominal collection(OR = 0.86, 95%CI: 0.63 to 1.17, P = 0.34), mortality(OR = 0.85, 95%CI: 0.57 to 1.27, P = 0.43), reoperation(OR = 0.91, 95%CI: 0.75 to 1.12, P = 0.38) or hospital length of stay(overall mean difference 0.11 d, 95%CI:-0.51 to 0.73, P = 0.72), when compared with no mechanical bowel preparation, nor when evidence from just randomized controlledtrials was analysed. A sub-analysis of mechanical bowel preparation vs absolutely no preparation or a single rectal enema similarly revealed no differences in clinical outcome measures. CONCLUSION In the most comprehensive meta-analysis of mechanical bowel preparation in elective colorectal surgery to date, this study has suggested that the use of mechanical bowel preparation does not affect the incidence of postoperative complications when compared with no preparation. Hence, mechanical bowel preparation should not be administered routinely prior to elective colorectal surgery. | Katie E Rollins Hannah Javanmard-Emamghissi Dileep N Lobo | 2018 | World Journal of Gastroenterology2018，24，4： | 33 |
| 4 | Update on Anti-Saccharomyces cerevisiae antibodies, anti-nuclear associated anti-neutrophil antibodies and antibodies to exocrine pancreas detected by indirect immunofluorescence as biomarkers in chronic inflammatory bowel diseases: Results of a multicent显示文摘AIM: Anti-Saccharomyces cerevisiae antibodies (ASCA), anti-nuclear associated anti-neutrophil antibodies (NANA) and antibodies to exocrine pancreas (PAB), are serological tools for discriminating Crohn’s disease (CrD) and ulcerative colitis (UC). Like CrD, coeliac disease (CoD) is an inflammatory bowel disease (IBD) associated with (auto) antibodies. Performing a multicenter study we primarily aimed to determine the performance of ASCA, NANA and PAB tests for IBD diagnosis in children and adults, and secondarily to evaluate the prevalence of these markers in CoD. METHODS: Sera of 109 patients with CrD, 78 with UC, 45 with CoD and 50 healthy blood donors were retrospectively included. ASCA, NANA and PAB were detected by indirect immunofluorescence (IIF). RESULTS: ASCA+/NANA- profile displayed a positive predictive value of 94.2% for CrD. Detection of ASCA was correlated with a more severe clinical profile of CrD and treatment of the disease did not influence their serum levels. ASCA positivity was found in 37.9% of active CoD.PAB were found in 36.7% CrD and 13.3% CoD patients and were not correlated with clinical features of CrD, except with an early onset of the disease. Fifteen CrD patients were ASCA negative and PAB positive. CONCLUSION: ASCA and PAB detected by IIF are specific markers for CrD although their presence does not rule out a possible active CoD. The combination of ASCA, NANA and PAB tests improves the sensitivity of immunological markers for CrD. Repeating ASCA, NANA, and PAB testing during the course of CrD has no clinical value. | S Desplat-Jégo C Johanet A Escande J Goetz N Fabien N Olsson E Ballot J Sarles JJ Baudon JC Grimaud M Veyrac P Chamouard RL Humbel | 2007 | World Journal of Gastroenterology2007，13，16： | 24 |
| 5 | OPTICAL PROPERTIES OF GeO_2 AND Ge NANOCRYSTALS显示文摘he co m pound m aterial of n m size particles Ge O2 Si O2 w as synthesied through hydrolysis of Si( O C2 H4) and Ge Cl4 . A heat treatm ent w as carried out for the sa m ples at 100 ~1200 ℃in air . Its optical property w as deter mined by U V Vis spectur m . We have found that theabsorption edge of spectru m shifted progressively to longer w avelengths . The quantu m size ef fect of nanocrystals appears because crystals gro w and energy of optical band gap reduces d ueto the influence of te m perature . By the analysis of X ray diffraction w e have observed theprocess in w hich the structure of particles changed fro m disorder into order . | Y.H.Zhou 1) ,Y.Y.Feng 2) and H.Y.Lu 2) 1)Department of Physics Nanjing Normal University, Nanjing 210097,China 2)Physics and Ch寁O P T I C A L P R O P E R T I E S O F Ge O2 A N D Ge N A N O C R Y S T A L S Y. H. Zhou1) , Y. Y. Feng2) | 1999 | Acta Metallurgica Sinica(English Letters)1999，12，5： | 22 |
| 6 | Experimental obstructive jaundice alters claudin-4 expression in intestinal mucosa: Effect of bombesin and neurotensin显示文摘瞄准:调查试验性的妨碍的黄疸和外长的 bombesin 和 neurotensin (NT )(BBS ) 的影响紧密的连接(TJ ) 的表示上的管理在老鼠的肠上皮的蛋白质 claudin-4。方法:四十只男 Wistar 老鼠随机被划分成五个组:我 = 控制, II = 假冒操作, III = 胆汁管结扎(BDL ) , IV = BDL+BBS (30 microg/kg 每 d ) , V = BDL+NT (300 microg/kg 每 d ) 。在 d 的实验的结束 10,内毒素在门和大动脉的血被测量。终端回肠的织物节组织学地被检验并且免疫组织化学地为在肠上皮的 claudin-4 表示的评估。结果:妨碍的黄疸导致了重要的门和大动脉的 endotoxemia 表明的肠的障碍失败。Claudin-4 表示显著地被增加在上面在 jaundiced 老鼠的第三根绒毛并且一起来它的侧面的分发的规定被注意。BBS 或 NT 的管理恢复了 claudin-4 表示到控制状态并且显著地减少了门和大动脉的 endotoxemia。结论:在肠上皮的试验性的妨碍的黄疸增加 claudin-4 表示,它可以是贡献粘膜障碍的混乱的一个关键因素。毁坏规章的肽 BBS, NT 能阻止这扇改变和还原剂门和全身的 endotoxemia。 | Stelios F Assimakopoulos Constantine E Vagianos Aristides S Charonis Ilias H Alexandris Iris Spiliopoulou Konstantinos C Thomopoulos Vassiliki N Nikolopoulou Chrisoula D Scopa | 2006 | World Journal of Gastroenterology2006，12，21： | 21 |
| 7 | 利用微卫星进行奶牛数量性状基因位点定位的研究显示文摘采用孙女设计法对德国奶牛的3个数量性状——产奶量、乳脂产量及乳蛋白产量进行了数量性状基因位点的定位研究。实验共有20个父系半同胞家系的1 130头种公牛,共测定了30对染色体上的229个微卫星,表型性状的育种值由孙代母牛估计得到。连锁分析采用多重遗传标记回归法,临界F值由置换实验法计算得到。统计检验发现在某些染色体上存在着一些显著的QTL’s区域,特别是14号染色体上某一区域对所有3个产奶性状都有极显著的影响。进一步证实了Coppieters和Ron等人的实验结果。 | 徐宁迎 H Thomsen N Reinsch C Looft E Kalm | 2000 | Acta Genetica Sinica2000，27，9： | 20 |
| 8 | 世界卫生组织(WHO)造血与淋巴组织肿瘤分类方案:临床顾问委员会会议报告显示文摘引言 :从 1995年开始 ,欧洲病理学工作者协会和血液病理学会一直致力于制定一个新的世界卫生组织 (WHO)血液恶性肿瘤分类方案 ,该分类方案包括淋巴系肿瘤、髓系肿瘤、组织细胞肿瘤和肥大细胞肿瘤。 材料与方法 :此项 WHO计划共组成十个病理学工作者委员会 ,负责确定病种和作出定义。另外还成立一个由国际血液学家和肿瘤学家组成的临床顾问委员会 (CAC)以保证该分类的临床实用性。 1997年 11月召开会议讨论了与该分类有关的临床问题。 结果 :WHO采纳了 1994年国际淋巴瘤研究组 (IL SG)报告的修订欧美淋巴系肿瘤分类 (REAL)方案作为淋巴系肿瘤的分类方案。该方案的分类方法遵循以下原则 :分类应是联合应用形态学、免疫表型、遗传特征及临床特征能够清楚界定的“真实存在”(“real”)病种的名录 ,上述各项特征的相对重要性因病种不同而异 ,不存在任何“金标准”。 WHO将 REAL分类原则延用于髓系肿瘤和组织细胞肿瘤 ,髓系肿瘤的分类包括联合应用细胞形态学和细胞遗传学异常能够界定的各个病种。围绕一系列临床问题召集的这次 CAC会议 ,就提交的大多数问题达成共识 ,这些问题及共识将详述于下。对于另外一些问题 ,CAC认为淋巴系肿瘤临床分组既无必要也不必需 ,患者的治疗取决于淋巴瘤的具体类型 ,如有? | N L Harris E S Jaffe J Diebold G Flandrin H K Muller-Hermelink J Vardiman T A Lister C D Bloomfield 张凤奎 郝玉书 | 2001 | 白血病.淋巴瘤2001，10，3： | 20 |
| 9 | Whole brain radiotherapy for the treatment of multiple brain metastases显示文摘 | Tsao M Lloyd N Wong R Chow E Rakovitch E Laperriere N | 2006 | 中国神经肿瘤杂志2006，4，2： | 17 |
| 10 | Cell Death Mechanisms Induced by Cytotoxic Lymphocytes显示文摘One of the functions of the immune system is to recognize and destroy abnormal or infected cells to maintain homeostasis. This is accomplished by cytotoxic lymphocytes. Cytotoxicity is a highly organized multifactor process. Here,we reviewed the apoptosis pathways induced by the two main cytotoxic lymphocyte subsets,natural killer(NK) cells and CD8+ T cells. In base to recent experimental evidence,we reviewed NK receptors involved in recognition of target-cell,as well as lytic molecules such as perforin,granzymes-A and-B,and granulysin. In addition,we reviewed the Fas-FasL intercellular linkage mediated pathway,and briefly the cross-linking of tumor necrosis factor(TNF) and TNF receptor pathway. We discussed three models of possible molecular interaction between lytic molecules from effector cytotoxic cells and target-cell membrane to induction of apoptosis. | Chávez-Galán L Arenas-Del Angel MC Zenteno E Chávez R Lascurain R | 2009 | Cellular & Molecular Immunology2009，6，1： | 17 |
| 11 | 幽门螺杆菌感染处理的当前观念——MaastrichtⅢ共识报告显示文摘名词缩写欧洲幽门螺杆菌研究小组:European Helicobacter Study Group,EHSG胃食管反流病:gastro-esophageal reflux disease。 | P Malfertheiner F Megraud C O'Morain F Bazzoli E El-Omar D Graham R Hunt T Rokkas N Vakil EJ Kuipers 朱琦 | 2007 | 胃肠病学2007，12，3： | 15 |
| 12 | 全面评估乳腺癌筛查的利与弊并指导乳腺癌的筛查显示文摘摘译:在美国乳腺癌是女性第二大恶性肿瘤的死亡病因,乳腺钼靶摄片可以降低乳腺癌的病死率,但同时可造成过度诊断等伤害。作者检索1960年1月1日—2014年1月19日关于乳腺钼靶摄片利与弊的相关研究论文,结果发现乳腺钼靶摄片筛查乳腺癌可使乳腺癌总体病死率下降19%, | 罗勇 Pace L E Keating N L | 2014 | 临床误诊误治2014，27，5： | 15 |
| 13 | SMARCA4表达缺失是诊断卵巢高钙血症型小细胞癌既敏感又特异性的指标显示文摘卵巢高钙血症型小细胞癌是一种非常罕见的卵巢肿瘤,好发于年轻女性,预后差。临床因其罕见并具有相对非特异性的组织学特征,仅依靠组织学诊断极具有挑战性。组织学上卵巢高钙血症型小细胞癌具有从经典的、最初描述的小细胞形态到含丰富嗜酸性胞质的大细胞形态,因此需与多种肿瘤实体进行鉴别诊断。 | Conlon N Silva A Guerra E 魏建国(摘译) 许春伟(审校) | 2016 | 临床与实验病理学杂志2016，32，7： | 15 |
| 14 | Platelets generated from human embryonic stem cells are functional in vitro and in the microcirculation of living mice显示文摘 | Shi-Jiang Lu Feng Li Hong Yin Qiang Feng Erin A Kimbrel Eunsil Hahm Jonathan N Thon Wei Wang Joseph E ltaliano Jaehyung Cho Robert Lanza | 2011 | Cell Research2011，21，3： | 14 |
| 15 | 猫叫综合征关键区域定位于5p15.2的D5S713-D5S18区域显示文摘猫叫综合征是由5号染色体短臂缺失引起的染色体缺失综合征。根据染色体综合征“关键区域”的概念,以及近10年来对106例5p缺失病例的临床诊断、细胞遗传学及分子遗传学分析,将猫叫综合征的关键区域定位于5p15.2,位于D5S713和D5S18两个遗传标记之间的区域。为研究该病提供了遗传学资料。 | 但美霞 Niebuhr A 张小晓 张秀清 李明月 戴理 高春生 贾开亮 赵非非 宋莉 叶珏 马绍武 施惠平 刘国仰 黄尚志 杨焕明 Udar N Niebuhr E 罗会元 | 1997 | 中华医学遗传学杂志1997，14，5： | 14 |
| 16 | 内脏脂肪组织通过产生骨桥蛋白调控成纤维细胞衰老促进心脏衰老显示文摘老化通过增加包括骨桥蛋白(osteopontin,OPN)在内的细胞外基质(extracellular matrix,ECM)蛋白的沉积引起心脏结构和功能改变进而导致进行性间质纤维化。虽然已知OPN参与各种病理状况,但其在心肌衰老中的作用仍不清楚。 | Sawaki D Czibik G Pini M Ternacle J Suffee N Mercedes R Marcelin G Surenaud M Marcos E Gual P Clément K Hue S Adnot S Hatem SN Tsuchimochi I Yoshimitsu T Hénégar C Derumeaux G 刘青 叶鹏 | 2018 | 中华高血压杂志2018，26，3： | 14 |
| 17 | 慢性肾脏病中的炎症和动脉硬化:慢性肾功能不全队列研究中的发现显示文摘慢性肾脏病(chronic kidney disease,CKD)和动脉硬化程度与心血管病发病率和死亡率增加相关。目前认为炎症在动脉硬化发展中发挥作用,而CKD被认为是一种促炎症反应的状态。CKD患者的动脉僵硬度增加,横断面数据提示CKD中增多的炎症标志物与较高动脉僵硬度值相关。 | Peyster E Chen J Feldman HI Go AS Gupta J Mitra N Pan Q Porter A Rahman M Raj D Reilly M Wing MR Yang W Townsend RR 陈云 叶鹏 | 2017 | 中华高血压杂志2017，25，11： | 12 |
| 18 | Epithelial ovarian cancer:An overview显示文摘Ovarian cancer is the second most common gyneco-logical cancer and the leading cause of death in the United States. In this article we review the diagnosis and current management of epithelial ovarian cancer which accounts for over 95 percent of the ovarian malignancies. We will present various theories about the potential origin of ovarian malignancies. We will discuss the genetic anomalies and syndromes that may cause ovarian cancers with emphasis on Breast cancer type 1/2 mutations. The pathology and pathogenesis of ovarian carcinoma will also be presented. Lastly, we provide a comprehensive overview of treatment strategies and staging of ovarian cancer, conclusions and future directions. | Arpita Desai Jingyao Xu Kartik Aysola Yunlong Qin Chika Okoli Ravipati Hariprasad Ugorji Chinemerem Candace Gates Avinash Reddy Omar Danner Geary Franklin Anachebe Ngozi Guilherme Cantuaria Karan Singh William Grizzle Charles Landen Edward E Partridge Valerie Montgomery Rice E Shyam P Reddy Veena N Rao | 2014 | World Journal of Translational Medicine2014，3，1： | 10 |
| 19 | Naringenin prevents experimental liver fibrosis by blocking TGFβ-Smad3 and JNK-Smad3 pathways显示文摘AIM To study the molecular mechanisms involved in the hepatoprotective effects of naringenin(NAR)on carbon tetrachloride(CCl4)-induced liver fibrosis.METHODS Thirty-two male Wistar rats(120-150 g)were randomly divided into four groups:(1)a control group(n=8)that received 0.7%carboxy methyl-cellulose(NAR vehicle)1 m L/daily p.o.;(2)a CCl4 group(n=8)that received 400 mg of CCl4/kg body weight i.p.3 times a week for 8 wk;(3)a CCl4+NAR(n=8)group that received 400 mg of CCl4/kg body weight i.p.3times a week for 8 wk and 100 mg of NAR/kg body weight daily for 8 wk p.o.;and(4)an NAR group(n=8)that received 100 mg of NAR/kg body weight daily for 8 wk p.o.After the experimental period,animals were sacrificed under ketamine and xylazine anesthesia.Liver damage markers such as alanine aminotransferase(ALT),alkaline phosphatase(AP),γ-glutamyl transpeptidase(γ-GTP),reduced glutathione(GSH),glycogen content,lipid peroxidation(LPO)and collagen content were measured.The enzymatic activity of glutathione peroxidase(GPx)was assessed.Liver histopathology was performed utilizing Masson’s trichrome and hematoxylin-eosin stains.Zymography assays for MMP-9 and MMP-2 were carried out.Hepatic TGF-β,α-SMA,CTGF,Col-I,MMP-13,NF-κB,IL-1,IL-10,Smad7,Smad3,p Smad3 and p JNK proteins were detected via western blot.RESULTS NAR administration prevented increases in ALT,AP,γ-GTP,and GPx enzymatic activity;depletion of GSH and glycogen;and increases in LPO and collagen produced by chronic CCl4 intoxication(P<0.05).Liver histopathology showed a decrease in collagen deposition when rats received NAR in addition to CCl4.Although zymography assays showed that CCl4 produced an increase in MMP-9 and MMP-2gelatinase activity;interestingly,NAR administration was associated with normal MMP-9 and MMP-2 activity(P<0.05).The anti-inflammatory,antinecrotic and antifibrotic effects of NAR may be attributed to its ability to prevent NF-κB activation and the subsequent production of IL-1 and IL-10(P<0.05).NAR completely prevented the increase in TGF-β,α-SMA,CTGF,Col-1,and MMP-13 proteins compared with the CCl4-treated group(P<0.05).NAR prevented Smad3phosphorylation in the linker region by JNK since this flavonoid blocked this kinase(P<0.05).CONCLUSION NAR prevents CCl4 induced liver inflammation,necrosis and fibrosis,due to its antioxidant capacity as a free radical inhibitor and by inhibiting the NF-κB,TGF-β-Smad3 and JNK-Smad3 pathways. | Erika Hernández-Aquino Natanael Zarco Sael Casas-Grajales Erika Ramos-Tovar Rosa E Flores-Beltrán Jonathan Arauz Mineko Shibayama Liliana Favari Víctor Tsutsumi José Segovia Pablo Muriel | 2017 | World Journal of Gastroenterology2017，23，24： | 10 |
| 20 | Role of the endothelium in inflammatory bowel diseases显示文摘Inflammatory bowel diseases(IBD) are a complex group of diseases involving alterations in mucosal immunity and gastrointestinal physiology during both initiation and progressive phases of the disease.At the core of these alterations are endothelial cells,whose continual adjustments in structure and function coordinate vascular supply,immune cell emigration,and regulation of the tissue environment.Expansion of the endothelium in IBD(angiogenesis),mediated by inflammatory growth factors,cytokines and chemokines,is a hallmark of active gut disease and is closely related to disease severity.The endothelium in newly formed or inflamed vessels differs from that in normal vessels in the production of and response to inflammatory cytokines,growth factors,and adhesion molecules,altering coagulant capacity,barrier function and blood cell recruitment in injury.This review examines the roles of the endothelium in the initiation and propagation of IBD pathology and distinctive features of the intestinal endothelium contributing to these conditions. | Walter E Cromer J Michael Mathis Daniel N Granger Ganta V Chaitanya J Steven Alexander | 2011 | World Journal of Gastroenterology2011，17，5： | 10 |
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