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| 1 | Abstract from: Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: A clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians显示文摘Description: The American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP) jointly developed this guideline to present the evidence and provide clinical recommendations based on the benefits and harms of higher versus lower blood pressure targets for the treatment of hypertension in adults aged 60 years or older. | Amir Qaseem Timothy J. Wilt Robert Rich Linda L. Humphrey Jennifer Frost Mary Ann Forciea | 2017 | Chinese Nursing Research2017，4，4： | 43 |
| 2 | Models and estimators linking individual-based and sample-based rarefaction, extrapolation and comparison of assemblages显示文摘Aims In ecology and conservation biology,the number of species counted in a biodiversity study is a key metric but is usually a biased underestimate of total species richness because many rare species are not detected.Moreover,comparing species richness among sites or samples is a statistical challenge because the observed number of species is sensitive to the number of individuals counted or the area sampled.For individual-based data,we treat a single,empirical sample of species abundances from an investigator-defined species assemblage or community as a reference point for two estimation objectives under two sampling models:estimating the expected number of species(and its unconditional variance)in a random sample of(i)a smaller number of individuals(multinomial model)or a smaller area sampled(Poisson model)and(ii)a larger number of individuals or a larger area sampled.For sample-based incidence(presence–absence)data,under a Bernoulli product model,we treat a single set of species incidence frequencies as the reference point to estimate richness for smaller and larger numbers of sampling units.Methods The first objective is a problem in interpolation that we address with classical rarefaction(multinomial model)and Coleman rarefaction(Poisson model)for individual-based data and with sample-based rarefaction(Bernoulli product model)for incidence frequencies.The second is a problem in extrapolation that we address with sampling-theoretic predictors for the number of species in a larger sample(multinomial model),a larger area(Poisson model)or a larger number of sampling units(Bernoulli product model),based on an estimate of asymptotic species richness.Although published methods exist for many of these objectives,we bring them together here with some new estimators under a unified statistical and notational framework.This novel integration of mathematically distinct approaches allowed us to link interpolated(rarefaction)curves and extrapolated curves to plot a unified species accumulation curve for empirical examples.We provide new,unconditional variance estimators for classical,individual-based rarefaction and for Coleman rarefaction,long missing from the toolkit of biodiversity measurement.We illustrate these methods with datasets for tropical beetles,tropical trees and tropical ants.Important Findings Surprisingly,for all datasets we examined,the interpolation(rarefaction)curve and the extrapolation curve meet smoothly at the reference sample,yielding a single curve.Moreover,curves representing 95%confidence intervals for interpolated and extrapolated richness estimates also meet smoothly,allowing rigorous statistical comparison of samples not only for rarefaction but also for extrapolated richness values.The confidence intervals widen as the extrapolation moves further beyond the reference sample,but the method gives reasonable results for extrapolations up to about double or triple the original abundance or area of the reference sample.We found that the multinomial and Poisson models produced indistinguishable results,in units of estimated species,for all estimators and datasets.For sample-based abundance data,which allows the comparison of all three models,the Bernoulli product model generally yields lower richness estimates for rarefied data than either the multinomial or the Poisson models because of the ubiquity of non-random spatial distributions in nature. | Robert K.Colwell Anne Chao Nicholas J.Gotelli Shang-Yi Lin Chang Xuan Mao Robin L.Chazdon John T.Longino | 2012 | Journal of Plant Ecology2012，5，1： | 37 |
| 3 | Safety of once‐daily insulin detemir in patients with type 2 diabetes treated with oral hypoglycemic agents in routine clinical practice (在常规临床实践中使用口服降糖药治疗的2型糖尿病患者每日一次使用地特胰岛素治疗的安全性)显示文摘 | Stuart Ross Grzegorz Dzida Qiuhe Ji Marcel Kaiser Robert Ligthelm Luigi Meneghini Avideh Nazeri Domingo Orozco‐Beltran Changyu Pan Anne Louise Svendsen | 2014 | Journal of Diabetes2014，，3： | 18 |
| 4 | 肿瘤恶性转化与C/EBPβ和STAT3基因相关(英文)显示文摘The inference of transcriptional networks that regulate transitions into physiological or pathological cellular states remains a central challenge in systems biology. A mesenchymal phenotype is the hallmark of tumour aggressiveness in human malignant glioma,but the regulatory programs responsible for implementing the associated molecular signature are largely unknown. Here we show that reverse-engineering and an unbiased interrogation of a glioma-specific regulatory network reveal the transcriptional module that activates expression of mesenchymal genes in malignant glioma. Two transcription factors (C/EBPβ and STAT3) emerge as synergistic initiators and master regulators of mesenchymal transformation. Ectopic co-expression of C/EBPβ and STAT3 reprograms neural stem cells along the aberrant mesenchymal lineage,whereas elimination of the two factors in glioma cells leads to collapse of the mesenchymal signature and reduces tumour aggressiveness. In human glioma,expression of C/EBPβ and STAT3 correlates with mesenchymal differentiation and predicts poor clinical outcome. These results show that the activation of a small regulatory module is necessary and sufficient to initiate and maintain an aberrant phenotypic state in cancer cells. | Maria Stella Carro Wei Keat Lim Mariano Javier Alvarez Robert J. Bollo Evan Y. Snyder Erik P. Sulman Sandrine L. Anne Fiona Doetsch Howard Colman Anna Lasorella Ken Aldape Andrea Califano Antonio Iavarone | 2010 | 中华神经外科疾病研究杂志2010，9，1： | 16 |
| 5 | ≥60岁高血压病人控制血压在较高或较低水平的药物治疗--美国医师协会和美国家庭医师学会临床实践指南显示文摘目的:针对≥60岁的高血压病人治疗中较高和较低降压目标的利弊,美国医师协会(ACP)和美国家庭医师学会(AAFP)共同制订了这一指南,为临床治疗提供证据及治疗建议。方法:本指南依据于已发表的主要疗效指标的随机对照试验以及针对危害的观察性研究的系统性评价。资料来源于EMBASE、系统性综述Cochrane数据库、MEDLINE和Clinical Trials.gov,搜索时间为从数据库建立开始至2015年1月,其中MEDLINE数据更新到2016年9月。评估指标包括全因死亡率、与卒中相关的发病率和死亡率、主要心脏事件(包括致死和非致死性心肌梗死和心源性猝死)和危害。本指南采用GRADE法(Grading of Recommendations,Assessment,Development,and Evaluation)对证据和建议进行分级。目标使用者和病人人群:本指南的目标使用者为所有临床医师,目标病人人群包括所有年龄≥60岁的高血压病人。建议1:对≥60岁、收缩压持续≥150mmHg(1mmHg=0.133kPa)的病人治疗时,ACP和AAFP建议临床医师应启动降压治疗以控制收缩压<150mmHg,从而减少死亡、脑卒中和心脏事件的风险(等级:强烈推荐,高质量证据)。对≥60岁高血压病人进行治疗时,建议临床医生定期与病人具体讨论降压目标的利弊,根据讨论情况选择治疗目标。建议2:对≥60岁的有脑卒中或短暂性脑缺血发作病史的病人,ACP和AAFP建议临床医生考虑启动或者加强药物治疗,以控制收缩压<140mmHg,降低脑卒中复发的风险(等级:弱推荐,中等质量证据)。对≥60岁高血压病人进行治疗时,建议临床医生定期与病人具体讨论降压目标的利弊,根据讨论情况选择治疗目标。建议3:对一部分≥60岁有高度心血管风险的病人,ACP和AAFP建议临床医生根据个体评估情况考虑启动或者强化降压药物治疗,控制收缩压到140mmHg以下,从而减少脑卒中或心脏事件发生的风险(等级:弱推荐,低质量证据)。对≥60岁高血压病人进行治疗时,建议临床医生定期与病人具体讨论降压目标的利弊,根据讨论情况选择治疗目标。 | Amir Qaseem Timothy J.Wilt Robert Rich Linda L.Humphrey Jennifer Frost Mary Ann Forciea | 2017 | 护理研究(下旬版)2017，31，8： | 8 |
| 6 | Identification of four novel DC-SIGN ligands on Mycobacterium bovis BCG显示文摘Dendritic-cell-specific intercellular adhesion molecule-3-grabbing non-integrin(DC-SIGN;CD209)has an important role in mediating adherence of Mycobacteria species,including M.tuberculosis and M.bovis BCG to human dendritic cells and macrophages,in which these bacteria can survive intracellularly.DC-SIGN is a C-type lectin,and interactions with mycobacterial cells are believed to occur via mannosylated structures on the mycobacterial surface.Recent studies suggest more varied modes of binding to multiple mycobacterial ligands.Here we identify,by affinity chromatography and mass-spectrometry,four novel ligands of M.bovis BCG that bind to DC-SIGN.The novel ligands are chaperone protein DnaK,60 kDa chaperonin-1(Cpn60.1),glyceraldehyde-3 phosphate dehydrogenase(GAPDH)and lipoprotein lprG.Other published work strongly suggests that these are on the cell surface.Of these ligands,lprG appears to bind DC-SIGN via typical proteinglycan interactions,but DnaK and Cpn60.1 binding do not show evidence of carbohydrate-dependent interactions.LprG was also identified as a ligand for DC-SIGNR(L-SIGN;CD299)and the M.tuberculosis orthologue of lprG has been found previously to interact with human toll-like receptor 2.Collectively,these findings offer new targets for combating mycobacterial adhesion and within-host survival,and reinforce the role of DCSIGN as an important host ligand in mycobacterial infection. | Maria V.Carroll Robert B.Sim Fabiana Bigi Anne Jäkel Robin Antrobus Daniel A.Mitchell | 2010 | Protein & Cell2010，1，9： | 7 |
| 7 | Radiofrequency ablation for early oesophageal squamous neoplasia:Outcomes form United Kingdom registry显示文摘AIM:To report outcomes on patients undergoing radiofrequency ablation(RFA)for early oesophageal squamous neoplasia from a National Registry.METHODS:A Prospective cohort study from 8 tertiary referral centres in the United Kingdom.Patients with squamous high grade dysplasia(HGD)and early squamous cell carcinoma(ESCC)confined to the mucosa were treated.Visible lesions were removed by endoscopic mucosal resection(EMR)before RFA.Following initial RFA treatment,patients were followed up 3monthly.Residual flat dysplasia was treated with RFA until complete reversal dysplasia(CR-D)was achieved or progression to invasive Squamous cell cancer defined as infiltration into the submucosa layer or beyond.The main outcome measures were CR-D at 12 mo from start of treatment,long term durability,progression to cancer and adverse events.RESULTS:Twenty patients with squamous HGD/ESCC completed treatment protocol.Five patients(25%)had EMR before starting RFA treatment.CR-D was 50%at12 mo with a median of 1 RFA treatment,mean 1.5(range 1-3).Two further patients achieved CR-D with repeat RFA after this time.Eighty per cent with CR-D remain dysplasia free at latest biopsy,with median follow up 24 mo(IQR 17-54).Six of 20 patients(30%)progressed to invasive cancer at 1 year.Four patients(20%)required endoscopic dilatations for symptomatic structuring after treatment.Two of these patients have required serial dilatations thereafter for symptomatic dysphagia with a median of 4 dilatations per patient.The other 2 patients required only a single dilatation to achieve an adequate symptomatic response.One patient developed cancer during follow up after end of treatment protocol.CONCLUSION:The role of RFA in these patients re-mains unclear.In our series 50%patients responded at12 mo.These figures are lower than limited published data. | Rehan J Haidry Mohammed A Butt Jason Dunn Matthew Banks Abhinav Gupta Howard Smart Pradeep Bhandari Lesley Ann Smith Robert Willert Grant Fullarton Morris John Massimo Di Pietro Ian Penman Marco Novelli Laurence B Lovat | 2013 | World Journal of Gastroenterology2013，19，36： | 7 |
| 8 | Annual report to the nation on the status of cancer, 1975‐2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates显示文摘 | Brenda K.Edwards ElizabethWard Betsy A.Kohler ChristieEheman Ann G.Zauber Robert N.Anderson AhmedinJemal Maria J.Schymura IrisLansdorp‐Vogelaar Laura C.Seeff Marjoleinvan Ballegooijen S. LuukGoede Lynn A. G.Ries | 2010 | Cancer2010，，3： | 6 |
| 9 | Management and outcome of hepatocellular adenoma with massive bleeding at presentation显示文摘AIM To evaluate outcome of acute management and risk of rebleeding in patients with massive hemorrhage due to hepatocellular adenoma(HCA). METHODS This retrospective cohort study included all consecutive patients who presented to our hospital with massive hemorrhage(grade Ⅱ or Ⅲ) due to ruptured HCA and were admitted for observation and/or intervention between 1999-2016. The diagnosis of HCA was based on radiological findings from contrastenhanced magnetic resonance imaging(MRI) or pathological findings from biopsy or resection of the HCA. Hemorrhage was diagnosed based on findings from computed tomography or MRI. Medical records were reviewed for demographic features, clinical presentation, tumor features, initial and subsequent management, short-and long-term complications and patient and lesion follow-up. RESULTS All patients were female(n = 23). Treatment in the acute phase consisted of embolization(n = 9, 39.1%), conservative therapy(n = 13, 56.5%), andother intervention(n = 1, 4.3%). Median hemoglobin level decreased significantly more on days 0-3 in the intervention group than in the patients initially treated conservatively(0.9 mmol/L vs 2.4 mmol/L respectively, P = 0.006). In total, 4 patients suffered severe shortterm complications, which included hypovolemic shock, acute liver failure and abscess formation. After a median follow-up of 36 mo, tumor regression in nonsurgically treated patients occurred with a median reduction of 76 mm down to 25 mm. Four patients underwent secondary(elective) treatment(i.e., tumor resection) to address HCA size of > 5 cm and/or desire for future pregnancy. One case of rebleeding was documented(4.3%). None of the patients experienced long-term complication(mean follow-up time: 36 mo). CONCLUSION With a 4.3% risk of rebleeding, secondary(elective) treatment of HCA after massive hemorrhage may only be considered in patients with persistent HCA > 5 cm. | Anne J Klompenhouwer Robert A de Man Maarten GJ Thomeer Jan NM Ijzermans | 2017 | World Journal of Gastroenterology2017，23，25： | 5 |
| 10 | NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer显示文摘 | Couturier-Maillard Aurélie Secher Thomas Rehman Ateequr Normand Sylvain De Arcangelis Adéle Haesler Robert Huot Ludovic Grandjean Teddy Bressenot Aude Delanoye-Crespin Anne Gaillot Olivier Schreiber Stefan Lemoine Yves Ryffel Bernhard Hot D | 2013 | Journal of Clinical Investigation2013，，2： | 5 |
| 11 | High prevalence of epilepsy in onchocerciasis endemic health areas in Democratic Republic of the Congo显示文摘Background:A high prevalence of epilepsy has been observed in many onchocerciasis endemic regions.This study is to estimate the prevalence of active epilepsy and exposure to Onchocerca volvulus infection in a rural population in Ituri province,Democratic Republic of Congo.Methods:In August 2016,a community-based cross-sectional study was conducted in an onchocerciasis endemic area in the rural health zone of Logo,Ituri Province.Households within two neighbouring health areas were randomly sampled.To identify persons with epilepsy,a three-stage approach was used.In the first stage,all individuals of the selected households were screened for epilepsy by non-medical field workers using a validated 5-item questionnaire.In the second and third stage,suspected cases of epilepsy were examined by non-specialist medical doctors,and by a neurologist,respectively.A case of epilepsy was defined according to the 2014 International League Against Epilepsy(ILAE)guidelines.Exposure to O.volvulus was assessed by testing for IgG4 antibodies to an O.volvulus antigen(OV16 Rapid Test,)in individuals aged 3 years and older.Results:Out of 1389 participants included in the survey,64 were considered to have active epilepsy(prevalence 4.6%)(95%confidence interval[CI]:3.6-5.8).The highest age-specific epilepsy prevalence estimate was observed in those aged 20 to 29 years(8.2%).Median age of epilepsy onset was 10 years,with a peak incidence of epilepsy in the 10 to 15 year-old age group.OV16 test results were available for 912 participants,of whom 30.5%(95%CI,27.6-33.6)tested positive.The prevalence of OV16 positivity in a village ranged from 8.6 to 68.0%.After adjusting for age,gender and ivermectin use,a significant association between exposure to onchocerciasis and epilepsy was observed(adjusted odds ratio=3.19,95%CI:1.63-5.64)(P<0.001).Conclusions:A high prevalence of epilepsy and a significant association between epilepsy and exposure to O.volvulus were observed in the population in Ituri province,Democratic Republic of Congo.There is an urgent need to implement a CDTI programme and to scale up an epilepsy treatment and care programme. | Evy Lenaerts Michel Mandro Deby Mukendi Patrick Suykerbuyk Housseini Dolo Deogratias Wonya’Rossi Françoise Ngave Chellafe Ensoy-Musoro Anne Laudisoit An Hotterbeekx Robert Colebunders | 2018 | Infectious Diseases of Poverty2018，7，1： | 5 |
| 12 | 关于与青光眼疾病严重性相关的资源使用和成本的一项多中心回顾性试验研究显示文摘目的:调查在不同疾病严重程度上青光眼治疗的资源消耗和直接成本。
设计:基于医学档案综述的观察性、回顾性的队列研究。 | Paul P. Lee John G. Walt John J. Doyle Sameer V. Kotak Stacy J. Evans Donald L. Budenz Philip P. Chen Anne L. Coleman Robert M. Feldman HenRY D. Jampel L.Jay Katz Richard P.Mills Jonathan S.Myers Robert J.Noecker Jody R.Piltz-Seymour Robert R.Ritch Paul N.Schacknow Janet B.Serle Gary L.Trick 范翔(译) | 2006 | 美国医学会眼科杂志(中文版)2006，18，4： | 4 |
| 13 | Gastrointestinal Microbiome Signatures of Pediatric Patients With Irritable Bowel Syndrome显示文摘 | Delphine M. Saulnier Kevin Riehle Toni–Ann Mistretta Maria–Alejandra Diaz Debasmita Mandal Sabeen Raza Erica M. Weidler Xiang Qin Cristian Coarfa Aleksandar Milosavljevic Joseph F. Petrosino Sarah Highlander Richard Gibbs Susan V. Lynch Robert J. Shulman | 2011 | Gastroenterology2011，，5： | 4 |
| 14 | Induction and Maintenance Therapy With Infliximab for Children With Moderate to Severe Ulcerative Colitis显示文摘 | Jeffrey Hyams Lakshmi Damaraju Marion Blank Jewel Johanns Cynthia Guzzo Harland S. Winter Subra Kugathasan Stanley Cohen James Markowitz Johanna C. Escher Gigi Veereman–Wauters Wallace Crandall Robert Baldassano Anne Griffiths | 2012 | Clinical Gastroenterology and Hepatology2012，，4： | 3 |
| 15 | Expression of Transforming Growth Factor-β1 by Pancreatic Stellate Cells and Its Implications for Matrix Secretion and Turnover in Chronic Pancreatitis显示文摘 | Fanny Wai-Tsing Shek Robert Christopher Benyon Fiona Mairi Walker Peter Raymond McCrudden Sylvia Lin Foon Pender Elizabeth Jean Williams Penelope Ann Johnson Colin David Johnson Adrian Calvin Bateman David Roger Fine John Peter Iredale | 2002 | The American Journal of Pathology2002，，5： | 2 |
| 16 | Model for end-stage liver disease (MELD) and allocation of donor livers显示文摘 | Russell Wiesner Erick Edwards Richard Freeman Ann Harper Ray Kim Patrick Kamath Walter Kremers John Lake Todd Howard Robert M. Merion Robert A. Wolfe Ruud Krom | 2003 | Gastroenterology2003，，1： | 2 |
| 17 | The Pan-ErbB Negative Regulator Lrig1 Is an Intestinal Stem Cell Marker that Functions as a Tumor Suppressor显示文摘 | Anne E. Powell Yang Wang Yina Li Emily J. Poulin Anna L. Means Mary K. Washington James N. Higginbotham Alwin Juchheim Nripesh Prasad Shawn E. Levy Yan Guo Yu Shyr Bruce J. Aronow Kevin M. Haigis Jeffrey L. Franklin Robert J. Coffey | 2012 | Cell2012，，1： | 2 |
| 18 | Evaluation of a locked nucleic acid form of antisense oligo targeting HIF-1α in advanced hepatocellular carcinoma显示文摘BACKGROUND Hypoxia-inducible factor 1α(HIF-1α) is a gene that regulates tumor survival,neovascularization and invasion. Overexpression of HIF-1α correlates with poor prognosis in hepatocellular carcinoma(HCC). RO7070179 is a HIF-1α inhibitor that decreases HIF-1α mRNA and its downstream targets, it could be a potential treatment in HCC.AIM To evaluate safety and preliminary activity of RO7070179 in patients with previously treated HCC, with focus on a patient with prolonged response to RO7070179.METHODS In the preclinical study of RO7070179 in a HCC xenograft model, the mice wereseparated into 4 groups with each group received doses of 0, 3, 10 and 30 mg/kg for total 10 doses. HCC patients who failed at least one line of systemic treatment,received RO7070179 as a weekly infusion, each cycle is 6 wk. We evaluated the safety and HIF-1α mRNA levels of RO7070179.RESULTS Preclinical evaluation of RO7070179 in orthotopic HCC xenograft model showed no significant differences in HCC tumor weight between the 3 and 10 mg/kg groups. However, dose of 10 mg/kg of RO7070179, has shown 76% reduction of the amount of HIF-1α mRNA in HCC tissue. In the phase 1 b study of RO7070179 in previously treated HCC patients, 8 out of 9 were evaluable: 1 achieved PR and1 SD. The patient with PR responded after 2 cycles treatments, which has been maintained for 12 cycles. This patient also showed reduction in perfusion of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI) after 1 cycle of treatment. After 1 cycle of treatment, both patients with PR and SD showed decrease in HIF-1α mRNA at the root of biopsies(each biopsy was divided into 2 specimens, the tip and the root).CONCLUSION RO7070179 can reduce HIF-1α mRNA level in HCC patients with SD or PR. It is well tolerated at 10 mg/kg, with transaminitis as the dose of increased toxicity.This study indicates that RO7070179 might benefit HCC patients, and an early signal for clinical benefit can potentially be predicted through changes in either m RNA level or DCE-MRI within 1 cycle of therapy. | Jennifer Wu Merly Contratto Krishna P Shanbhogue Gulam A Manji Bert H O'Neil Anne Noonan Robert Tudor Ray Lee | 2019 | World Journal of Clinical Oncology2019，10，3： | 2 |
| 19 | 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines显示文摘 | Neil J. Stone Jennifer G. Robinson Alice H. Lichtenstein C. Noel Bairey Merz Conrad B. Blum Robert H. Eckel Anne C. Goldberg David Gordon Daniel Levy Donald M. Lloyd-Jones Patrick McBride J. Sanford Schwartz Susan T. Shero Sidney C. Smith Karol Watson Pet | 2014 | Circulation (_suppl_ Suppl)2014，，25： | 2 |
| 20 | Distinct antifibrogenic effects of erlotinib,sunitinib and sorafenib on rat pancreatic stellate cells显示文摘AIM:To study if three clinically available small molecule kinase inhibitors(SMI),erlotinib,sunitinib and sorafenib,exert antifibrogenic effects on pancreatic stellate cells(PSC)and analyze the basis of their action.METHODS:Cultured rat PSC were exposed to SMI.Cell proliferation and viability were assessed employing 5-bromo-2’-deoxyuridine incorporation assay and flow cytometry,respectively.2-Deoxy-2-[18F]fluoroglucose(18F-FDG)uptake was measured to study metabolic activity.Exhibition of the myofibroblastic PSC phenotype was monitored by immunofluorescence analysis ofα-smooth muscle actin(α-SMA)expression.Levels of mRNA were determined by real-time PCR,while protein expression and phosphorylation were analyzed by immunoblotting.Transforming growth factor-β1 (TGF-β1)levels in culture supernatants were quantified by ELISA.RESULTS:All three SMI inhibited cell proliferation and18F-FDG uptake in a dose-dependent manner and without significant cytotoxic effects.Furthermore,additive effects of the drugs were observed.Immunoblot analysis showed that sorafenib and sunitib,but not erlotinib,efficiently blocked activation of the AKT pathway,while all three drugs displayed little effect on phosphorylation of ERK1/2.Cells treated with sorafenib or sunitinib expressed less interleukin-6 mRNA as well as less collagen type 1 mRNA and protein.Sorafenib was the only drug that also upregulated the expression of matrix metalloproteinase-2 and reduced the secretion of TGF-β1 protein.All three drugs showed insignificant or discordant effects on the mRNA and protein levels ofα-SMA.CONCLUSION:The tested SMI,especially sorafenib,exert inhibitory effects on activated PSC,which should be further evaluated in preclinical studies. | Anne Elsner Falko Lange Brit Fitzner Martin Heuschkel Bernd Joachim Krause Robert Jaster | 2014 | World Journal of Gastroenterology2014，20，24： | 2 |
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