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| 1 | GRADE:证据质量和推荐强度分级的共识显示文摘GRADE工作组致中国读者:推荐分级的评估、制定与评价(GRADE)工作组已取得长足进步。我们制定了系列指南文件,除发表文章外,该非正式组织已经发展成为一个评价证据、转化卫生保健领域知识用以指导决策者的智囊团。80余位国际专家研究和制定了该评价系统。正如其他科学一样,证据评价和指南制定科学不会停滞不前。经过十年发展,GRADE的工作将借助中国Cochrane中心的推广在中国的卫生保健领域更加广为人知。GRADE工作组的成员期待与中国的指南制定组织、方法学家、临床医生和决策者合作,实现我们的共同目标:人人享有更好的卫生保健。中国Cochrane中心翻译GRADE工作组在BMJ上发表的系列文章,是朝这个方向迈出的重要一步,也是对下一步在中国推广GRADE工作的直接贡献。感兴趣的读者可登录我们的网站www.gradeworkinggroup.org和在以下网址获取我们的软件GRADEprohttp://gffzz73f9075754ca43bbhnbpxxwqqokb66w5f.ffgz.tsg.suse.edu.cn. | Gordon H Guyatt Andrew D Oxman Gunn E Vist Regina Kunz Yngve Falck-Ytter Pablo Alonso-Coello Holger J Schünemann GRADE工作组 陈佩贤 陈耀龙 李幼平 | 2009 | 中国循证医学杂志2009，9，1： | 60 |
| 2 | GRADE:从证据到推荐显示文摘GRADE系统将指南中的推荐分为强弱两级。本文旨在探索这种分级的含义及对患者、临床医生、政策制定者各自的意义。 | Gordon H Guyatt Andrew D Oxman Regina Kunz Yngve Falck-Ytter Gunn E Vist Alessandro Liberati Holger J Schünemann 谭培勇 陈耀龙 李幼平 | 2009 | 中国循证医学杂志2009，9，3： | 26 |
| 3 | Pancreatic ductal adenocarcinoma: Risk factors, screening, and early detection显示文摘Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with over 38000 deaths in 2013. The opportunity to detect pancreatic cancer while it is still curable is dependent on our ability to identify and screen high-risk populations before their symptoms arise. Risk factors for developing pancreatic cancer include multiple genetic syndromes as well as modifiable risk factors. Genetic conditions include hereditary breast and ovarian cancer syndrome, Lynch Syndrome, familial adenomatous polyposis, Peutz-Jeghers Syndrome, familial atypical multiple mole melanoma syndrome, hereditary pancreatitis, cystic fibrosis, and ataxia-telangiectasia; having a genetic predisposition can raise the risk of developing pancreatic cancer up to 132-fold over the general population. Modifiable risk factors, which include tobacco exposure, alcohol use, chronic pancreatitis, diet, obesity, diabetes mellitus, as well as certain abdominal surgeries and infections, have also been shown to increase the risk of pancreatic cancer development. Several largevolume centers have initiated such screening protocols, and consensus-based guidelines for screening high-riskgroups have recently been published. The focus of this review will be both the genetic and modifiable risk factors implicated in pancreatic cancer, as well as a review of screening strategies and their diagnostic yields. | Andrew E Becker Yasmin G Hernandez Harold Frucht Aimee L Lucas | 2014 | World Journal of Gastroenterology2014，20，32： | 24 |
| 4 | Model for end-stage liver disease score versus Child score in predicting the outcome of surgical procedures in patients with cirrhosis显示文摘AIM:To determine factors affecting the outcome of patients with cirrhosis undergoing surgery and to compare the capacities of the Child-Turcotte-Pugh(CTP) and model for end-stage liver disease(MELD)score to predict that outcome. METHODS:We reviewed the charts of 195 patients with cirrhosis who underwent surgery at two teaching hospitals over a five-year period.The combined endpoint of death or hepatic decompensation was considered to be the primary endpoint. RESULTS:Patients who reached the endpoint had a higher MELD score,a higher CTP score and were more likely to have undergone an urgent procedure.Among patients undergoing elective surgical procedures,no statistically significant difference was noted in the mean MELD(12.8±3.9 vs 12.6±4.7,P=0.9)or in the mean CTP(7.6±1.2 vs 7.7±1.7,P=0.8)between patients who reached the endpoint and those who did not.Both mean scores were higher in the patients reaching the endpoint in the case of urgent procedures(MELD:22.4± 8.7 vs 15.2±6.4,P=0.0007;CTP:9.9±1.8 vs 8.5±1.8, P=0.008).The performances of the MELD and CTP scores in predicting the outcome of urgent surgery were only fair,without a significant difference between them (AUC=0.755±0.066 for MELD vs AUC=0.696±0.070 for CTP,P=0.3). CONCLUSION:The CTP and MELD scores performedequally,but only fairly in predicting the outcome of urgent surgical procedures.Larger studies are needed to better define the factors capable of predicting the outcome of elective surgical procedures in patients with cirrhosis. | Maarouf A Hoteit Amaar H Ghazale Andrew J Bain Eli S Rosenberg Kirk A Easley Frank A Anania Robin E Rutherford | 2008 | World Journal of Gastroenterology2008，14，11： | 16 |
| 5 | GRADE:什么是“证据质量”?为什么它对临床医生重要?显示文摘指南制定者们利用各式各样的系统对证据质量进行分级,并据此给出他们的推荐意见。但这些分级系统有些过于简单,有的不易理解,还有的尽管详细却很复杂。 | Gordon H Guyatt Andrew D Oxman Regina Kunz Gunn E Vist Yngve Falck-Ytter Holger J Schünemann 陈柳 陈耀龙 李幼平 | 2009 | 中国循证医学杂志2009，9，2： | 12 |
| 6 | Borderline resectable pancreatic cancer: Definitions and management显示文摘Pancreatic cancer is the fourth leading cause of cancer death in the United States. While surgical resection remains the only curative option, more than 80% of patients present with unresectable disease. Unfortunately, even among those who undergo resection, the reported median survival is 15-23 mo, with a 5-year survival of approximately 20%. Disappointingly, over the past several decades, despite improvements in diagnostic imaging, surgical technique and chemotherapeutic options, only modest improvements in survival have been realized. Nevertheless, it remains clear that surgical resection is a prerequisite for achieving longterm survival and cure. There is now emerging consensus that a subgroup of patients, previously considered poor candidates for resection because of the relationship of their primary tumor to surrounding vasculature, may benefit from resection, particularly when preceded by neoadjuvant therapy. This stage of disease, termed borderline resectable pancreatic cancer, has become of increasing interest and is now the focus of a multiinstitutional clinical trial. Here we outline the history, progress, current treatment recommendations, and future directions for research in borderline resectable pancreatic cancer. | Nicole E Lopez Cristina Prendergast Andrew M Lowy | 2014 | World Journal of Gastroenterology2014，20，31： | 11 |
| 7 | Effects of Glomus mosseae on the toxicity of heavy metals to Vicia faba显示文摘A glasshouse pot experiment was conducted to investigate effects of th e arbuscular mycorrhizal fungus Glomus mosseae on the growth of Vicia faba and t oxicity induced by heavy metals (HMs) (Cu, Zn, Pb and Cd) in a field soil contam inated by a mixture of these metals. There was also uninoculation treatment (NM) simultaneously. Mycorrhizal (GM) plants have significantly increased growth and tolerance to toxicity induced by heavy metals compared with NM plants. P uptake was significantly increased in GM plants. Mycorrhizal symbiosis reduced the tra nsportation of HMs from root to shoot by immobilizing HMs in the mycorrhizal, sh own by increasing the ratios of HMs from root to shoot. Oxidative stress, which can induce DNA damage, is an important mechanism of heavy metal toxicity. GM tre atment decreased oxidative stress by intricating antioxidative systems such as p eroxidases and non-enzymic systems including soluble protein. The DNA damage ind uced by heavy metals was detected using comet assay, which showed DNA damage in the plants was decreased by the GM treatment. | ZHANG Xu-hong LIN Ai-jun CHEN Bao-dong WANG You-shan SMITH Sally E SMITH F Andrew | 2006 | Journal of Environmental Sciences2006，18，4： | 10 |
| 8 | 欧洲血管外科学会指南:第二部分——颈动脉狭窄患者的诊断和检查显示文摘在此,我们呈献颈动脉狭窄患者脑血管事件二级预防的欧洲血管外科学会指南,包括降脂治疗、抗血小板治疗以及其他危险因素控制。这些推荐均基于现有的临床试验证据。对颈动脉病患者需要采取积极的预防性治疗。我们还讨论了颈动脉狭窄的诊断和分级。 | Christos D. Liapis Sir Peter F. Bell Dimitri P. Mikhailidis Juharli Sivenius Andrew Nicolaides Jose Femandes e Fernandes Giorgio Biasi Ears Norgrer 赵颖(译) 谭泽锋(译) 徐安定(译) | 2011 | 国际脑血管病杂志2011，19，7： | 9 |
| 9 | Evolution of surgical skills training显示文摘外科的训练正在变化:100 年传统被法律、道德的担心为耐心的安全,工作小时限制,手术室时间的费用,和复杂并发症正在质问。训练的外科的模拟和技巧提供一个机会在在生活病人上尝试他们前在手术室环境外面教并且练习先进技巧。当使用真实仪器和录像设备操作在一个盒子训练员模仿了“织物”,模拟训练能向前是同样直的。更先进的、虚拟现实模拟器现在为普遍使用可得到、准备好了。早系统表明了他们的有效性和歧视的能力。更新的系统启用全面课程和完整的程序的模拟的开发。医药教育是的毕业生的认证委员会(ACGME ) 要求了训练和评估的新奇方法的发展。外科的组织正在打电话让方法保证技巧的维护,并且,进展 surgical 训练信任外科医生作为技术上能干。在他们的当前的形式的模拟器被表明了改进外科的居民的手术室表演。训练课程标准化的开发仍然是一个迫切、重要的议程,特别地为最小的侵略外科。一条创新、进步的途径,从航空的域借经验,能为外科的训练的下一个世纪提供基础,保证产品的质量。当技术发展,我们练习的方法将继续演变,到医生和病人的利益。 | Kurt E Roberts Robert L Bell Andrew J Duffy | 2006 | World Journal of Gastroenterology2006，12，20： | 8 |
| 10 | 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 |
| 11 | 欧洲血管外科学会指南:第1部分——颈动脉狭窄患者的预防显示文摘在此,我们呈献颈动脉狭窄患者脑血管事件二级预防的欧洲血管外科学会指南,包括降脂治疗、抗血小板治疗以及其他危险因素控制。这些推荐均基于现有的临床试验证据。对颈动脉疾病患者需要采取积极的预防性治疗。我们还讨论了颈动脉狭窄的诊断和分级。 | Christos D. Liapis Sir Peter F. Bell Dimitri P. Mikhailidis Juhani Sivenius Andrew Nicolaides Jose Femandes e Fernandes Giorgio Biasi Lars Norgren 董大伟(译) 刘小艳(译) 徐安定(译) | 2011 | 国际脑血管病杂志2011，19，6： | 7 |
| 12 | Oral eplerenone for the management of chronic central serous chorioretinopathy显示文摘AIM: To examine eplerenone(Inspra, Pfizer), a mineralocorticoid receptor antagonist, as a treatment option for chronic central serous chorioretinopathy(CSCR).METHODS: A retrospective consecutive case series was conducted for patients receiving oral eplerenone for chronic CSCR. At baseline and each follow-up visit,spectral domain optical coherence tomography(SD-OCT)imaging was performed, including manual measurements of the height and diameter size of subretinal fluid. The primary outcome measure was the reduction in subretinal fluid following initiation of therapy.RESULTS: A total of 17 eyes of 13 patients treated with25 and 50 mg of oral eplerenone per day were identified.Subretinal fluid(SRF) decreased over time following eplerenone therapy(P = 0.007 and P =0.002, diameter and height respectively). Maximum SRF height decreased from a mean of 131.5 μm at baseline to 15.3 μm at day181+. SRF diameter decreased from an average of 2174.4μm at baseline to 46.9 μm at day 181 +. Log MAR visual acuity improved from 0.42(Snellen equivalent: 20/53) at baseline to 0.29(Snellen equivalent: 20/39) at day 181 +(P = 0.024). Central subfield thickness(CST) decreased from 339.5 μm at baseline to 270.3 μm at day 181+(P = 0.029).CONCLUSION: Eplerenone therapy resulted in significant anatomic and visual improvements in eyes with chronic CSCR. | Rishi P Singh Jonathan E Sears Rumneek Bedi Andrew P Schachat Justis P Ehlers Peter K Kaiser | 2015 | International Journal of Ophthalmology(English edition)2015，8，2： | 6 |
| 13 | 澳大利亚人乳头状瘤病毒疫苗计划实施5年对年轻人群生殖器疣患病情况的影响:国家调查数据分析显示文摘目的评估2007年中开始的澳大利亚人乳头状瘤病毒(HPV)疫苗计划对生殖器疣患病情况的影响。设计国家调查数据趋势分析。数据来源数据收集于2004--2011年度澳大利亚8所性健康服务机构;其中2所最大的临床中心收集了自我报告的本中心2009年度HPV疫苗现状。研究对象2004--2011年度首次就诊的85770名澳大利亚出生的国民;其中7686(9.0%)名患生殖器疣。主要结局测量比较前疫苗时期(2004—2007年中)和疫苗时期(2007年中-2001年末)不同人群生殖器疣新发病率变化趋势。结果疫苗时期21岁以下和21~30岁女性诊断患有生殖器疣的比例明显下降,发病率分别从2007年度的11.5%和11.3%下降至2011年度的0.85%和3.1%,P均〈0.001。在30岁以上的女性中未发现发病率的明显下降。在21岁以下和21~30岁异性恋男性人群中疫苗时期生殖器疣的发病率较前疫苗时期明显下降,分别由2007年度12.1%和18.2%下降至2011年度2.2%和8.9%,P均〈0.001。30岁以上的异性恋男性人群中发病率无明显下降。2011年235名21岁以下女性在使用HPV疫苗后无新发生殖器疣病例。结论年轻女性生殖器疣发病率的显著下降和2011年度部分年轻女性使用疫苗后的零发病率,说明HPV疫苗获得实验室外的良好功效。异性恋男性生殖器疣发病率的显著下降可能是由于群体免疫所致。 | Hammad Ali,lecturer Basil Donovan, professor HandanWand,senior lecturer Tim R H Read, sexual health physician David G Regan,senior lecturer Andrew E Grulich, professor Christopher K FaMey, professor Rebecca J Guy, associate professor 尹婕(译) 潘凌亚(校) | 2013 | 英国医学杂志中文版2013，16，4： | 4 |
| 14 | Controversies in the treatment of gastroesophageal reflux and achalasia显示文摘胃的食道的倒流疾病(GERD ) 和弛缓不能的有效治疗为这二作为标准答案建立了最小的侵略外科的 laparoscopic 外科的巨大的成功与更低的病态和死亡调节,更短的医院停留,更快的康复,和不太手术后的疼痛。在 GERD 的处理的一争吵作为比较喜欢的处理在 laparoscopic 反倒流外科(LARS ) 附近演变让 Barrett 的食管和过程的潜力减少食管的腺癌的风险。GERD 也与呼吸症状,气喘和喉的损害被联系了,并且第二争吵推动全部或部分的 fundoplication 是否是为 GERD 的更适当的处理的讨论。在 GERD 的处理的一种新、有希望的选择是 endoluminal 治疗。这种新处理选择的三种类型将被讨论:送到更低的食道的括约肌的射频精力,在胃的食道的连接的一个机械障碍的创造,并且更低的食道的括约肌的直接内视镜的紧缩。Laparoscopic 外科为弛缓不能为 GERD 而且同样永久的痊愈作为很有效的治疗被讨论不仅。这评论为弛缓不能分析三种很重要的处理选择:药,灵魂膨胀,和外科的治疗。因为他们的短半衰期和可变吸收,在弛缓不能的处理的药同样唯一的真非侵略的选择由于穷人不象 LARS 一样有效食道的倒空。第二种处理选择,灵魂膨胀,包含拉长更低的食管并且是仍然为弛缓不能考虑了最有效的非外科的处理。最后,为弛缓不能的外科的治疗和有关这个 laparoscopic 处理的二主要争吵被讨论。第一包含肌切开术被扩大到到胃上的程度,并且第二使反倒流过程的必要性和类型担心在肌切开术以后阻止 GERD。LARS 和 laparoscopic Heller 肌切开术是同意了在之上作为为 GERD 和弛缓不能的外科疗法的标准答案分别地。在一位富有经验的 laparoscopic 外科医生的手里,两个是为有有至少 90% 耐心的满足的优秀主观、客观的长期的结果的病人的安全、有效的治疗。 | Kurt E Roberts Andrew J Duffy Robert L Bell | 2006 | World Journal of Gastroenterology2006，12，20： | 4 |
| 15 | 临床致病性不动杆菌的分子生物学鉴定显示文摘目的对临床致病性不动杆菌进行种属鉴定,并比较3种方法(44℃生长试验、特异性引物PCR扩增和16SrRNA测序)对鲍曼不动杆菌鉴定的特异性、准确性及应用价值。方法收集临床致病不动杆菌56株,首先接种在胰蛋白胨大豆肉汤中44℃进行培养,观察是否可以生长;其次,提取56株不动杆菌基因组DNA,用两组不同的特异性引物进行PCR扩增鉴定;最后,用通用引物对56株不动杆菌的16SrRNA进行测序鉴定。结果 56株不动杆菌中有17株可在44℃生长。经特异性引物PCR扩增鉴定,发现8株鲍曼不动杆菌和3株13TU型不动杆菌均可在44℃中较早较快生长。金标准16SrRNA测序确定56株不动杆菌中含有9个种,其中鲍曼不动杆菌和13TU型不动杆菌的鉴定结果与特异性引物PCR扩增法相同。结论应用分子生物学方法鉴定鲍曼不动杆菌具有准确、高效且可重复性高的优点,尤其是特异性PCR扩增法,可作为较难诊断的鲍曼不动杆菌的首选鉴定方法。 | 韩蕾 张旭燕 韩少山 MCCARRON Andrew MOORE John E MILLAR Cherie B 徐纪茹 | 2012 | 西安交通大学学报(医学版)2012，33，5： | 4 |
| 16 | Update on medical and surgical options for patients with acute severe ulcerative colitis: what is new?显示文摘Acute severe ulcerative colitis(UC) is a highly morbid con dition that requires both medical and surgical managementhrough the collaboration of gastroenterologists and colorectal surgeons. First line treatment for patients presenting with acute severe UC consists of intravenous steroids, but those who do not respond require escalation of therapy or emergent colectomy. The mortality of emergent colectomy has declined significantly in recent decades, but due to the morbidity of this procedure, second line agents such as cyclosporine and infliximab have been used as salvage therapy in an attempt to avoid emergent surgery. Unfortunately, protracted medical therapy has led to patients presenting for surgery in a poorer state of health leading to poorer post-operative outcomes. In this era of multiple medical modalities available in the treatment of acute severe UC, physicians must consider the advantages and disadvantages of prolonged medical therapy in an attempt to avoid surgery. Colectomy remains a mainstay in the treatment of severe ulcerative colitis not responsive to corticosteroids and rescue therapy, and timely referral for surgery allows for improved post-operative outcomes with lower risk of sepsis and improved patient survival. Options for reconstructive surgery include three-stage ileal pouchanal anastomosis or a modified two-stage procedure that can be performed either open or laparoscopically. The numerous avenues of medical and surgical therapy have allowed for great advances in the treatment of patients with UC. In this era of options, it is important to maintain a global view, utilize biologic therapy when indicated, and then maintain an appropriate threshold for surgery. The purpose of this review is to summarize the growing number of medical and surgical options available in the treatment of acute, severe UC. | Rachel E Andrew Evangelos Messaris | 2016 | World Journal of Gastrointestinal Surgery2016，8，9： | 4 |
| 17 | Critical analysis of feeding jejunostomy following resection of upper gastrointestinal malignancies显示文摘AIM To assess nutritional recovery,particularly regarding feeding jejunostomy tube(FJT)utilization,following upper gastrointestinal resection for malignancy. METHODS A retrospective review was performed of a prospectively-maintained database of adult patients who underwent esophagectomy or gastrectomy(subtotal or total)for cancer with curative intent,from January 2001 to June 2014. Patient demographics,the approach to esophagectomy,the extent of gastrectomy,FJT placement and utilization at discharge,administration of parenteral nutrition(PN),and complications were evaluated. All patients were followed for at least ninety days or until death.RESULTS The 287 patients underwent upper GI resection,comprised of 182 esophagectomy(n=107 transhiatal,58.7%; n=56 Ivor-Lewis,30.7%)and 105 gastrectomy [n=63 subtotal(SG),60.0%; n=42 total(TG),40.0%]. 181 of 182 esophagectomy patients underwent FJT,compared with 47 of 105 gastrectomy patients(99.5% vs 44.8%,P < 0.0001),of whom most had undergone TG(n=39,92.9% vs n=8 SG,12.9%,P < 0.0001). Median length of stay was similar between esophagectomy and gastrectomy groups(14.7 d vs 17.1 d,P=0.076). Upon discharge,87 esophagectomy patients(48.1%)were taking enteral feeds,with 53(29.3%)fully and 34(18.8%)partially dependent. Meanwhile,20 of 39 TG patients(51.3%)were either fully(n=3,7.7%)or partially(n=17,43.6%)dependent on tube feeds,compared with 5 of 8 SG patients(10.6%),all of whom were partially dependent. Gastrectomy patients were significantly less likely to be fully dependent on tube feeds at discharge compared to esophagectomy patients(6.4% vs 29.3%,P=0.0006). PN was administered despite FJT placement more often following gastrectomy than esophagectomy(n=11,23.4% vs n=7,3.9%,P=0.0001). FJT-specific complications requiring reoperation within 30 d of resection occurred more commonly in the gastrectomy group(n=6),all after TG,compared to 1 esophagectomy patient(12.8% vs 0.6%,P=0.0003). Six of 7 patients(85.7%)who experienced tube-related complications required PN.CONCLUSION Nutritional recovery following esophagectomy and gastrectomy is distinct. Operations are associated with unique complication profiles. Nutritional supplementation alternative to jejunostomy should be considered in particular scenarios. | Andrew M Blakely Saad Ajmal Rachel E Sargent Thomas T Ng Thomas J Miner | 2017 | World Journal of Gastrointestinal Surgery2017，9，2： | 4 |
| 18 | 外用辣椒素治疗慢性疼痛:系统性综述显示文摘评价局部应用辣椒素治疗神经及肌肉骨骼功能失调引起的慢性疼痛的疗效和安全性。 | Lorna Mason R Andrew Moore Sheena Derry Jayne E Edwards Henry J Mcquay 孙静 | 2004 | 英国医学杂志中文版2004，7，5： | 3 |
| 19 | To stay or to leave: Stem cells and progenitor cells navigating the S1P gradient显示文摘Most hematopoietic stem progenitor cells (HSPCs) reside in bone marrow (BM), but a small amount of HSPCs have been found to circulate between BM and tissues through blood and lymph. Several lines of evidence suggest that sphingosine-1-phosphate (S1P) gradient triggers HSPC egression to blood circulation after mobilization from BM stem cell niches. Stem cells also visit certain tissues. After a temporary 36 h short stay in local tissues, HSPCs go to lymph in response to S1P gradient between lymph and tissue and eventually enter the blood circulation. S1P also has a role in the guidance of the primitive HSPCs homing to BM in vivo, as S1P analogue FTY720 treatment can improve HSPC BM homing and engraftment. In stress conditions, various stem cells or progenitor cells can be attracted to local injured tissues and participate in local tissue cell differentiation and tissue rebuilding through modulation the expression level of S1P1, S1P2 or S1P3 receptors. Hence, S1P is important for stem cells circulation in blood system to accomplish its role in body surveillance and injury recovery. | Andrew Hsu Jen-Fu Lee Daniel E Cramer Menq-Jer Lee | 2011 | World Journal of Biological Chemistry2011，2，1： | 3 |
| 20 | Macrophage secretory products induce an inflammatory phenotype in hepatocytes显示文摘AIM:To investigate the influence of macrophages on hepatocyte phenotype and function.METHODS:Macrophages were differentiated from THP-1 monocytes via phorbol myristate acetate stimulation and the effects of monocyte or macrophageconditioned medium on HepG2 mRNA and protein expression determined.The in vivo relevance of these findings was confirmed using liver biopsies from 147 patients with hepatitis C virus(HCV)infection.RESULTS:Conditioned media from macrophages,but not monocytes,induced a transient morphological change in hepatocytes associated with upregulation of vimentin(7.8±2.5-fold,P=0.045)and transforming growth factor(TGF)-β1(2.6±0.2-fold,P<0.001)and downregulation of epithelial cadherin(1.7±0.02-fold,P=0.017)mRNA expression.Microarray analysis revealed significant upregulation of lipocalin-2(17-fold,P <0.001)and pathways associated with inflammation,and substantial downregulation of pathways related to hepatocyte function.In patients with chronic HCV,realtime polymerase chain reaction and immunohistochemistry confirmed an increase in lipocalin-2 mRNA(F0 1.0 ±0.3,F1 2.2±0.2,F2 3.0±9.3,F3/4 4.0±0.8,P= 0.003)and protein expression(F1 1.0±0.5,F2 1.3± 0.4,F3/4 3.6±0.4,P=0.014)with increasing liver injury.High performance liquid chromatography-tandem mass spectrometry analysis identified elevated levels of matrix metalloproteinase(MMP)-9 in macrophageconditioned medium,and a chemical inhibitor of MMP-9 attenuated the change in morphology and mRNA expression of TGF-β1(2.9±0.2 vs 1.04±0.1,P<0.001) in macrophage-conditioned media treated HepG2 cells.In patients with chronic HCV infection,hepatic mRNA expression of CD163(F0 1.0±0.2,F1/2 2.8±0.3,F3/4 5.3±1.0,P=0.001)and MMP-9(F0 1.0±0.4,F1/2 2.8±0.3,F3/4 4.1±0.8,P=0.011)was significantly associated with increasing stage of fibrosis.CONCLUSION:Secreted macrophage products alter the phenotype and function of hepatocytes,with increased expression of inflammatory mediators,suggesting that hepatocytes actively participate in liver injury. | Michelle Melino Victoria L Gadd Gene V Walker Richard Skoien Helen D Barrie Dinesh Jothimani Leigh Horsfall Alun Jones Matthew J Sweet Gethin P Thomas Andrew D Clouston Julie R Jonsson Elizabeth E Powell | 2012 | World Journal of Gastroenterology2012，18，15： | 3 |
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