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1Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma.显示文摘Abrey LE Batchelor TT Ferreri A J Gospodarowicz M Pulczynski EJ Zucca E Smith JR Korfel A Soussain C DeAngelis LM Neuwelt EA O′Neill BP Thiel E Shenkier T Graus F van den Bent M Seymour JF Poortmans P Armitage JO Cavalli F 2005中国神经肿瘤杂志2005,3,3:53
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
3AGNP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
4Update 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 2007World Journal of Gastroenterology2007,13,16:24
5美国国立老化研究所与阿尔茨海默病协会诊断指南写作组:阿尔茨海默病临床前阶段的定义显示文摘阿尔茨海默病(AD)的病理生理过程在痴呆诊断的多年前就开始了。这一长期的AD“临床前”阶段是治疗干预的关键机会,但需进一步阐明AD的病理级联过程和临床症状出现之间的联系。美国国立老化研究所和AD协会召集了一个国际工作组对AD生物标志物、流行病学和神经心理学的证据进行综述并提出建议,以确定能够预测由“正常”认知到轻度认知功能障碍(MCI)及AD痴呆的最佳预测指标。根据目前已有的主要科学证据,我们提出了一个概念性的框架和用于操作的研究标准,以通过纵向临床研究来验证和改进这些模型。这些建议仅用于研究目的,目前不涉及临床应用。我们希望这些建议能提供一个共识,以推进临床前AD的研究,最终推动更早期治疗干预的进展,使得一些疾病减缓药物的疗效发挥最大。Sperling RA Aisen PS Beckett LA Bennett DA Craft S Fagan AM Iwatsubo T Jack CR Jr Kaye J Montine TJ Park DC Reiman EM Rowe CC Siemers E Stern Y Yaffe K Carrillo MC Thies B Morrison-Bogorad M Wagster MV Phelps CH 贾建平(译) 郭起浩(译) 黄丽(译) 陆璐(译) 张逸驰(译) 邢怡(译) 2012中华神经科杂志2012,45,5:22
6珠江、流溪河大型底栖动物分布和氮磷因子的相关分析显示文摘采用Anova、多重比较并t检验的方法来比较氮、磷因子和大型底栖动物在 3个河段 (流溪河、珠江西航道及前航道 )的显著性差异分布及它们之间的相关。结果显示 ,主要污染物均为NH+4 -N ,均高出国家地表水水质V级标准。前航道NO-3 -N和NO-2 -N含量最低 ,硝化作用和河流自净作用大大地降低。PO3-4 -P也是前航道、西航道的污染因子。NH+4 -N和PO3-4 -P不是生物分布的限制因子 ,底栖动物计数和河流底层的NO-3-N ,NO-2 -N呈显著负相关关系。必须进行氮和磷的污染控制及治理 ,才可能提高河流底栖动物多样性 ,提高生态环境质量。刘玉 VERMAAT J E RUYTER E D de KRUIJF H A M de 2003中山大学学报(自然科学版)2003,42,1:22
7下肢浅静脉治疗术后的加压疗法:美国静脉论坛血管、外科学会、美国静脉学会、血管医学学会和国际静脉联盟的临床实践指南显示文摘一、指南的由来下肢浅静脉治疗术后应用压力治疗的方式是几代血管外科医师多年临床经验积累所得,现主要应用于大隐静脉剥脱术、下肢静脉点状剥脱术及静脉硬化治疗等。目前单就静脉硬化治疗而言,术后压力治疗的推荐也是基于相关文献及实验验证[1],但对于其他术式,尤其是对于大隐静脉的热消融术,目前还没有形成规范统一的建议,这也使得当前的压力治疗具有很大的临床差异性。Lurie F Lal BK Antignani PL Blebea J Bush R Caprini J Davies A Forrestal M Jacobowitz G Kalodiki E Killewich L Lohr J Ma H Mosti G Partsch H Rooke T Wakefield T 李丹(译) 陈程浩(译) 牛传强(译) 张靖(译) 黄建忠(译) 2020中华介入放射学电子杂志2020,8,4:16
8ISO_BMWP底栖动物监测法在中国河流有机污染评价中的修正及应用显示文摘河流有机污染是我国目前特别严重的环境污染问题之一。可以采用化学或生物监测的方法进行评价。首次采用大型底栖动物BMWP(BiologicalMonitoringWorkingParty)系统方法,对广州珠江前航道、西航道和流溪河下游段共3个河段进行有机污染生物监测评价。结果显示:底栖动物在3河段间分布确有显著性差异,根据修正的BMWP分数可以判断流溪河水质相对较好,水质级别相应于中国地表水环境质量标准Ⅳ~Ⅴ级,西航道和前航道水质级别均为Ⅴ级。通过测试这一方法能成功地应用在珠江及流溪河,且修正后的ISO_BMWP法可以较好地匹配于我国地表水5级评价系统,因此,初步认为修正后的ISO_BMWP系统可以成为一个和化学监测互补的好方法,从而应用于中国河流的生物监测评价。刘玉 VERMAAT J E RUYTER E D de KRUIJF H A M de 2004中山大学学报(自然科学版)2004,43,4:15
9高血压患者脑小血管病变化对认知功能的影响显示文摘高血压是脑小血管病进展与认知功能障碍的主要危险因素之一。该研究旨在探讨高血压患者脑小血管病损伤变化与认知功能减退及轻度认知功能障碍的关系。该研究的数据从ISSYS队列(探讨高血压无症状性脑卒中:一个磁共振成像研究)中获得,其是一项纵向人群研究,纳入基线无痴呆及脑卒中,年龄50~70岁的高血压患者。Jiménez-Balado J Riba-Llena I Abril O Garde E Penalba A Ostos E Maisterra O Montaner J Noviembre M Mundet X Ventura O Pizarro J Delgado P 赵狄 练桂丽 2019中华高血压杂志2019,27,2:15
10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
11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
12低雾化低挥发性汽车用新型聚氨酯泡沫塑料助剂显示文摘康普顿公司开发了一系列适用于消除或减少汽车内饰件中胺扩散或雾化的添加剂 ,其中包括快速、有效的生产用零扩散催化剂和低雾化表面活性剂。该系列添加剂能大大降低泡沫制品中的胺扩散 ,与异氰酸酯和多元醇原料能组成最佳组合 ,以保持良好的泡沫物理性能。Muller L Ghobary H E Derderian E J Robinson K K Chong S M 2003聚氨酯工业2003,18,3:9
13牧草如何生长——植物生长与放牧管理之关联(英文)显示文摘适当管理饲料饲草资源的基本原则是理解多年生牧草如何生长。长期以来 ,对根系生长有了基本的了解 ,对去叶和环境对根系生长的影响也知之甚多。然而 ,对去叶、干旱及其他环境因素对多年生牧草的影响以及这些牧草对去叶的反应缺乏应有的理解。从牧草返青到开花 ,植物处于短枝阶段 ,适度放牧并不对多年生牧草的健康和活力造成危害 ,因为植物会弥补其失去的叶片。然而 ,当牧草从短枝向长枝阶段 (节间伸长和开花期 )转移时 ,碳水化合物主要用于节间伸长和开花过程。在开花后和休眠前期 ,碳水化合物主要向茎基和植物基部转移 ,以供来年新枝条的发育。因此 ,在花后和休眠前期 ,放牧系统必须被调节到“无放牧”状态。“无放牧”状态 ,如休息、轮牧、延迟轮牧和快速轮牧制 ,其价值在于这种定期的禁牧可提高多年生牧草的活力 ,改善草地的健康状况 ,并且在不利的环境条件下 。Ronald E Sosebee David B Wester J Carlos Villalobos Carlton M Britton Changgui Wan Hisham Nofal 2005草业学报2005,14,1:8
14Orally administered extract from Prunella vulgaris attenuates spontaneous colitis in mdr1a^(-/-) mice显示文摘AIM: To investigate the ability of a Prunella vulgaris(P. vulgaris) ethanolic extract to attenuate spontaneous typhlocolitis in mdr1a-/- mice. METHODS: Vehicle(5% ethanol) or P. vulgaris ethanolic extract(2.4 mg/d) were administered daily by oral gavage to mdr1a-/- or wild type FVBWT mice from 6 wk of age up to 20 wk of age. Clinical signs of disease were noted by monitoring weight loss. Mice experiencingweight loss in excess of 15% were removed from the study. At the time mice were removed from the study, blood and colon tissue were collected for analyses that included histological evaluation of lesions, inflammatory cytokine levels, and myeloperoxidase activity. RESULTS: Administration of P. vulgaris extracts to mdr1a-/- mice delayed onset of colitis and reduced severity of mucosal inflammation when compared to vehicle-treated mdr1a-/- mice. Oral administration of the P. vulgaris extract resulted in reduced(P < 0.05) serum levels of IL-10(4.6 ± 2 vs 19.4 ± 4), CXCL9(1319.0 ± 277 vs 3901.0 ± 858), and TNFα(9.9 ± 3 vs 14.8 ± 1) as well as reduced gene expression by more than two-fold for Ccl2, Ccl20, Cxcl1, Cxcl9, IL-1 α, Mmp10, VCAM-1, ICAM, IL-2, and TNFα in the colonic mucosa of mdr1a-/- mice compared to vehicle-treated mdr1a-/-mice. Histologically, several microscopic parameters were reduced(P < 0.05) in P. vulgaris-treated mdr1a-/-mice, as was myeloperoxidase activity in the colon(2.49 ± 0.16 vs 3.36 ± 0.06, P < 0.05). The numbers of CD4+ T cells(2031.9 ± 412.1 vs 5054.5 ± 809.5) and germinal center B cells(2749.6 ± 473.7 vs 4934.0 ± 645.9) observed in the cecal tonsils of P. vulgaris-treated mdr1a-/- were significantly reduced(P < 0.05) from vehicle-treated mdr1a-/- mice. Vehicle-treated mdr1a-/- mice were found to produce serum antibodies to antigens derived from members of the intestinal microbiota, indicative of severe colitis and a loss of adaptive tolerance to the members of the microbiota. These serum antibodies were greatly reduced or absent in P. vulgaris-treated mdr1a-/- mice. CONCLUSION: The anti-inflammatory activity of P. vulgaris ethanolic extract effectively attenuated the severity of intestinal inflammation in mdr1a-/- mice.Kelley MK Haarberg Meghan J Wymore Brand Anne-Marie C Overstreet Catherine C Hauck Patricia A Murphy Jesse M Hostetter Amanda E Ramer-Tait Michael J Wannemuehler 2015World Journal of Gastrointestinal Pharmacology and Therapeutics2015,6,4:8
15重症败血症患者炎性介质水平对预后的影响显示文摘目的 :探索可早期预测败血症预后的炎性介质指标。方法 :前瞻性研究 ,观察期 2 8日 ,分析重症败血症患者与死亡相关的临床和实验室指标。结果 :共连续观察 2 6例 ,死亡 14例 (5 3.8%) ,且多死于研究阶段的第1周内 (74.0 %)。死亡组患者血总胆红素水平、4项全身炎性反应综合征 (SIRS)指标的积分和循环中的细胞间黏附分子 1(s ICAM 1)水平明显高于死亡组 ,其它炎性因子包括一些细胞因子和黏附分子的水平在 2组间差异不大。结论 :败血症患者的 s ICAM赵擎宇 张春玲 黄子通 M A Weigand H J Bardenheuer E Martin 2001中国危重病急救医学2001,13,11:7
16汽车采用的无级变速功率分流变速器的设计显示文摘在汽车应用方面提出了无级变速功率分流变速箱的一种设想 ,该装置由两可变速带轮 (变速器 )和一行星齿轮系所谓太阳轮和内齿圈三转动构件组合而成。“功率分流”的布置特点是输入轴同时把功率传到太阳轮和主动带轮 ,并通过变速器传到行星齿轮传动的内齿圈。因为输入轴传递的输入功率一分为二 (传到太阳轮和主动带轮 ) ,变速器中仅通过输入轴总功率流的一小部分 ,行星齿轮传动的第三转动件 (转臂 )收集了由内齿圈和太阳轮传来的功率流 ,把总功率传到输出轴传到车辆。该特徵提高了发动机功率在汽车应用的许可范围 ,该特徵特别在低速 -高转矩情况下提供无级变速可变传动比的范围时还降低了与动力传动有关的功率损失。建立一个所谓“增益系数”,用它通过变速箱的可变速元件和速比间隔来确定总功率流的两个分量的大小。用一外齿轮箱可以在发动机和变速箱的最佳范围内扩展无级变速范围。提出了一个采用外啮合有级齿轮传动 (同步变速器 )实现有效传动比间隔的无级变速范围应用于汽车的设计程序 。V H Mucino Z Lu J E Smith M Kimcikiewicz B Cowan 2004传动技术2004,18,1:7
17诊断性试验和策略的证据质量和推荐强度的分级显示文摘GRADE系统能对诊断性试验或策略的证据质量和推荐强度进行分级。本文旨在阐释在此过程中如何考虑患者的重要结局,Holger J Schünemann Andrew D Oxman Jan Brozek Paul Glasziou Roman Jaeschke Gunn E Vist John W Williams Jr Regina Kunz Jonathan Craig Victor M Montori Patrick Bossuyt Gordon H Guyatt 李晓 黄程 陈耀龙 李幼平 2009中国循证医学杂志2009,9,5:7
18Alternatives for large-scale production of cultured beef: A review显示文摘Cultured beef is a method where stem cells from skeletal muscle of cows are cultured in vitro to gain edible muscle tissue. For large-scale production of cultured beef, the culture technique needs to become more efficient than today's 2-dimensional(2D) standard technique that was used to make the first cultured hamburger. Options for efficient large-scale production of stem cells are to culture cells on microcarriers, either in suspension or in a packed bed bioreactor, or to culture aggregated cells in suspension. We discuss the pros and cons of these systems as well as the possibilities to use the systems for tissue culture. Either of the production systems needs to be optimized to achieve an efficient production of cultured beef. It is anticipated that the optimization of large-scale cell culture as performed for other stem cells can be translated into successful protocols for bovine satellite cells resulting in resource and cost efficient cultured beef.Matilda S M Moritz Sanne E L Verbruggen Mark J Post 2015Journal of Integrative Agriculture2015,14,2:7
19如何设计高质量针刺临床研究:基于证据的专家共识显示文摘本针刺随机对照试验(Randomised controlled trials, RCT)专家共识是基于目前针刺试验面临的最普遍、最关键问题,由临床医生、研究人员、从事针灸和外科的临床试验专家、统计专家、临床流行病学和方法学专家以及患者组成的国际临床研究小组联合制订。该共识将有助于临床试验资助者、注册者以及期刊编辑等评估针刺RCT方案及研究结果的相关性、重要性和质量。张誉清 焦睿珉 Claudia M Witt 劳力行 刘建平 Lehana Thabane Karen J Sherman Mike Cummings Dawn P Richards Eun-Kyung Anna Kim Tae-Hun Kim Myeong Soo Lee Michael E Wechsler Benno Brinkhaus Jun J Mao Caroline A Smith 岗卫娟 刘保延 刘志顺 刘岩 郑晖 吴佳霓 AloBSO Carrasco-Labra Mohit Bhandari Philip J Devereaux 景向红 Gordon Guyatt 2022英国医学杂志中文版2022,25,6:7
20Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease显示文摘AIM To determine if manipulation of dietary advanced glycation end product(AGE), intake affects nonalcoholic fatty liver disease(NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol(HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mR NA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content(a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/-animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD.Christopher Leung Chandana B Herath Zhiyuan Jia Sof Andrikopoulos Bronwyn E Brown Michael J Davies Leni R Rivera John B Furness Josephine M Forbes Peter W Angus 2016World Journal of Gastroenterology2016,22,35:7
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