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| 1 | Double-stranded DNA in exosomes: a novel biomarker in cancer detection显示文摘 | Basant Kumar Thakur Haiying Zhang Annette Becker Irina Matei Yujie Huang Bruno Costa-Silva Yan Zheng Ayuko Hoshino Helene Brazier Jenny Xiang Caitlin Williams Ruth Rodriguez-Barrueco Jose M Silva Weijia Zhang Stephen Hearn Olivier Elemento Navid Paknejad Katia Manova-Todorova Karl Welte Jacqueline Bromberg Hector Peinado David Lyden | 2014 | Cell Research2014，24，6： | 98 |
| 2 | Inflammation and fibrosis in chronic liver diseases including nonalcoholic fatty liver disease and hepatitis C显示文摘At present chronic liver disease(CLD),the third commonest cause of premature death in the United Kingdom is detected late,when interventions are ineffective,resulting in considerable morbidity and mortality.Injury to the liver,the largest solid organ in the body,leads to a cascade of inflammatory events.Chronic inflammation leads to the activation of hepatic stellate cells that undergo transdifferentiation to become myofibroblasts,the main extra-cellular matrix producing cells in the liver;over time increased extra-cellular matrix production results in the formation of liver fibrosis.Although fibrogenesis may be viewed as having evolved as a“wound healing”process that preserves tissue integrity,sustained chronic fibrosis can become pathogenic culminating in CLD,cirrhosis and its associated complications.As the reference standard for detecting liver fibrosis,liver biopsy,is invasive and has an associated morbidity,the diagnostic assessment of CLD by non-invasive testing is attractive.Accordingly,in this review the mechanisms by which liver inflammation and fibrosis develop in chronic liver diseases are explored to identify appropriate and meaningful diagnostic targets for clinical practice.Due to differing disease prevalence and treatment efficacy,disease specific diagnostic targets are required to optimally manage individual CLDs such as non-alcoholic fatty liver disease and chronic hepatitis C infection.To facilitate this,a review of the pathogenesis of both conditions is also conducted.Finally,the evidence for hepatic fibrosis regression and the mechanisms by which this occurs are discussed,including the current use of antifibrotic therapy. | Sudeep Tanwar Freya Rhodes Ankur Srivastava Paul M Trembling William M Rosenberg | 2020 | World Journal of Gastroenterology2020，26，2： | 17 |
| 3 | Choledochal cysts: Similarities and differences between Asian and Western countries显示文摘Choledochal cysts(CCs)are rare bile duct dilatations,intra-and/or extrahepatic,and have higher prevalence in the Asian population compared to Western populations.Most of the current literature on CC disease originates from Asia where these entities are most prevalent.They are thought to arise from an anomalous pancreaticobiliary junction,which are congenital anomalies between pancreatic and bile ducts.Some similarities in presentation between Eastern and Western patients exist such as female predominance,however,contemporary studies suggest that Asian patients may be more symptomatic on presentation.Even though CC disease presents with an increased malignant risk reported to be more than 10%after the second decade of life in Asian patients,this risk may be overstated in Western populations.Despite this difference in cancer risk,management guidelines for all patients with CC are based predominantly on observations reported from Asia where it is recommended that all CCs should be excised out of concern for the presence or development of biliary tract cancer. | George N Baison Morgan M Bonds William S Helton Richard A Kozarek | 2019 | World Journal of Gastroenterology2019，25，26： | 16 |
| 4 | Anterior knee pain following primary total knee arthroplasty显示文摘Despite improvements in technique and technology for total knee arthroplasty(TKA),anterior knee pain impacts patient outcomes and satisfaction.Addressing the prosthetic and surgical technique related causes of pain after TKA,specifically as it relates to anterior knee pain,can aid surgeons in addressing these issues with their patients.Design features of the femoral and patellar components which have been reported as pain generators include: Improper femoral as well as patellar component sizing or designs that result in patellofemoral stuffing; a shortened trochlear groove distance from the flange to the intercondylar box; and then surgical technique related issues resulting in: Lateral patellar facet syndrome; overstuffed patella/flange combination; asymmetric patellar resurfacing,improper transverse plane component rotation resulting in patellar subluxation/tilt.Any design consideration that allows impingement of extensor mechanism anatomical elements has the possibility of impacting outcome by becoming a pain generator.As the number of TKA procedures continues to increase,it is increasingly critical to develop improved,evidence based prostheses that maximize function and patient satisfaction while minimizing pain and other complications. | David Shervin Katelyn Pratt Travis Healey Samantha Nguyen William M Mihalko Mouhanad M El-Othmani Khaled J Saleh | 2015 | World Journal of Orthopedics2015，6，10： | 15 |
| 5 | Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study显示文摘 | Patrick Marcellin Edward Gane Maria Buti Nezam Afdhal William Sievert Ira M Jacobson Mary Kay Washington George Germanidis John F Flaherty Raul Aguilar Schall Jeffrey D Bornstein Kathryn M Kitrinos G Mani Subramanian John G McHutchison E Jenny Heathcote | 2012 | The Lancet2012，，： | 14 |
| 6 | 高危患者目标血压与心血管病预后显示文摘指南推荐血压目标值应〈140/90 mmHg(1mmHg=0.133kPa)以减少心血管事件的发生。但与其他心血管病预后(如冠状动脉事件)相比,包括脑卒中及心力衰竭在内的心血管病预后与收缩压下降关系更密切。一些心血管事件(如冠状动脉事件)风险在收缩压低时亦增高,风险-收缩压关系呈J形曲线,而脑卒中与血压不是J形曲线关系。 | B?hm M Schumacher H Teo KK Lonn EM Mahfoud F Mann JF Mancia G Redon J Schmieder RE Sliwa K Weber MA Williams BYusuf S 曲浥晨 叶鹏 | 2017 | 中华高血压杂志2017，25，6： | 14 |
| 7 | Factors associated with time to laparoscopic cholecystectomy for acute cholecystitis显示文摘AIM: To determine patient and process of care factors associated with performance of timely laparoscopic cholecystectomy for acute cholecystitis. METHODS: A retrospective medical record review of 88 consecutive patients with acute cholecystitis was conducted. Data collected included demographic data, co-morbidities, symptoms and physical findings at presentation, laboratory and radiological investigations, length of stay, complications, and admission service (medical or surgical). Patients not undergoing cholecystectomy during this hospitalization were excluded from analysis. Hierarchical generalized linear models were constructed to assess the association of pre-operative diagnostic procedures, presenting signs, and admitting service with time to surgery.RESULTS: Seventy cases met inclusion and exclusion criteria, among which 12 were admitted to the medical service and 58 to the surgical service. Mean ± SD time to surgery was 39.3 ± 43 h, with 87% of operations performed within 72 h of hospital arrival. In the adjusted models, longer time to surgery was associated with number of diagnostic studies and endoscopic retrograde cholangio-pancreatography (ERCP, P = 0.01) as well with admission to medical service without adjustment for ERCP (P < 0.05). Patients undergoing both magnetic resonance cholangiopancreatography (MRCP) and computed tomography (CT) scans experienced the longest waits for surgery. Patients admitted to the surgical versus medical service underwent surgery earlier (30.4 ± 34.9 vs 82.7 ± 55.1 h, P < 0.01), had less post-operative complications (12% vs 58%, P < 0.01), and shorter length of stay (4.3 ± 3.4 vs 8.1 ± 5.2 d, P < 0.01).CONCLUSION: Admission to the medical service and performance of numerous diagnostic procedures, ERCP, or MRCP combined with CT scan were associated with longer time to surgery. Expeditious performance of ERCP and MRCP and admission of medically stable patients with suspected cholecystitis to the surgical service to speed up time to surgery should be considered. | Chris N Daniak David Peretz Jonathan M Fine Yun Wang Alan K Meinke William B Hale | 2008 | World Journal of Gastroenterology2008，14，7： | 13 |
| 8 | Abdominal applications of diffusion-weighted magnetic resonance imaging: Where do we stand?显示文摘Diffusion-weighted imaging (DWI) is one of the magnetic resonance imaging (MRI) sequences providing qualitative as well as quantitative information at a cellular level. It has been widely used for various applications in the central nervous system. Over the past decade, various extracranial applications of DWI have been increasingly explored, as it may detect changes even before signal alterations or morphological abnormalities become apparent on other pulse sequences. Initial results from abdominal MRI applications are promising, particularly in oncological settings and for the detection of abscesses. The purpose of this article is to describe the clinically relevant basic concepts of DWI, techniques to perform abdominal DWI, its analysis and applications in abdominal visceral MR imaging, in addition to a brief overview of whole body DWI MRI. | Ajaykumar C Morani Khaled M Elsayes Peter S Liu William J Weadock Janio Szklaruk Jonathan Russell Dillman Asra Khan Thomas L Chenevert Hero K Hussain | 2013 | World Journal of Radiology2013，5，3： | 12 |
| 9 | Precore/basal core promoter mutants and hepatitis B viral DNA levels as predictors for liver deaths and hepatocellular carcinoma显示文摘AIM: To conduct a retrospective study in 400 chronic hepatitis B patients in order to identify hepatitis B viral factors associated with complications of liver disease or development of hepatocellular carcinoma.METHODS: The mean follow-up time was 83.6 ± 39.6 mo. Alpha-fetoprotein test and abdominal ultrasound were used for cancer surveillance. Hepatitis B basal core promoter mutants, precore mutants, genotypes, hepatitis B viral DNA (HBV DNA) level and hepatitis B e antigen (HBeAg) were measured. Univariate analysis and logistic regression were used to assess odds ratios for viral factors related to liver deaths and hepatocellular carcinoma development. RESULTS: During follow-up, 38 patients had liver deaths not related to hepatocellular carcinoma. On multivariate analysis, older age [odds ratio: 95.74 (12.13-891.31); P < 0.0001], male sex [odds ratio: 7.61 (2.20-47.95); P = 0.006], and higher log10 HBV DNA [odds ratio: 4.69 (1.16-20.43); P < 0.0001] were independently predictive for these liver related deaths. Also, 31 patients developed hepatocellular carcinoma. Multivariate analysis showed that older age [odds ratio: 26.51 (2.36-381.47); P = 0.007], presence of precore mutants [odds ratio: 4.23 (1.53-19.58); P = 0.02] and presence of basal core promoter mutants [odds ratio: 2.93 (1.24-7.57); P = 0.02] were independent predictors for progression to hepatocellular carcinoma.CONCLUSION: Our results show that high levels of baseline serum HBV DNA are associated with non- hepatocellular carcinoma-related deaths of liver failure, while genetic mutations in the basal core promoter and precore regions are predictive for development of hepatocellular carcinoma. | Myron J Tong Lawrence M Blatt Jia-Horng Kao Jason Tzuying Cheng William G Corey | 2006 | World Journal of Gastroenterology2006，12，41： | 11 |
| 10 | Metformin does not improve survival in patients with hepatocellular carcinoma显示文摘AIM:To assess whether metformin,which has a chemopreventive effect in chronic liver disease,has any chemotherapeutic effect in hepatocellular carcinoma.METHODS:This was a retrospective study of 701 patients with newly diagnosed hepatocellular carcinoma(HCC)seen between January 2005 and June 2011 at Mayo Clinic,Rochester,Minnesota.This patient cohort was a part of the global HCC BRIDGE study,which is a large longitudinal study of HCC determining the realworld experience of HCC characteristics,management and patient outcomes.We defined significant metformin exposure as continuation of this agent at least 90d beyond diagnosis of HCC,and compared survival of diabetic patients on metformin to diabetic patients not on metformin and non-diabetics.RESULTS:Our cohort was 72.9%male,with a mean±SD age of 62.6±12.3 years.The most common etiologies of liver disease were hepatitis C(34%),alcoholic liver disease(29%),fatty liver disease(15%)and hepatitis B(9%).By univariate analysis,using diabetics not on metformin as the reference group,diabetic patients with HCC on metformin had no survival advantage,with a HR(95%CI)of 1.0(0.8-1.3).Non-diabetic HCC patients also did not appear to have a survival advantage as compared to diabetic HCC patients not on metformin,as demonstrated by a HR(95%CI)of1.1(0.7-1.7).Diabetics on metformin beyond 90 d after HCC diagnosis had a longer median survival at 34.2 mo,as compared to 25.5 mo among diabetic patients who were not on metformin or had discontinued metformin within 90 d after HCC diagnosis.This finding was likely due to potential survival bias among those who lived long enough to receive metformin.CONCLUSION:Although the literature suggests a chemotherapeutic effect in other malignancies,our study demonstrates no survival benefit to the use of metformin in diabetic patients with HCC. | Mamatha Bhat Roongruedee Chaiteerakij William S Harmsen Cathy D Schleck Ju Dong Yang Nasra H Giama Terry M Therneau Gregory J Gores Lewis R Roberts | 2014 | World Journal of Gastroenterology2014，20，42： | 11 |
| 11 | Global kinematics of tectonic plates and subduction zones since the late Paleozoic Era显示文摘Detailed global plate motion models that provide a continuous description of plate boundaries through time are an effective tool for exploring processes both at and below the Earth's surface. A new generation of numerical models of mantle dynamics pre-and post-Pangea timeframes requires global kinematic descriptions with full plate reconstructions extending into the Paleozoic(410 Ma). Current plate models that cover Paleozoic times are characterised by large plate speeds and trench migration rates because they assume that lowermost mantle structures are rigid and fixed through time. When used as a surface boundary constraint in geodynamic models, these plate reconstructions do not accurately reproduce the present-day structure of the lowermost mantle. Building upon previous work, we present a global plate motion model with continuously closing plate boundaries ranging from the early Devonian at 410 Ma to present day.We analyse the model in terms of surface kinematics and predicted lower mantle structure. The magnitude of global plate speeds has been greatly reduced in our reconstruction by modifying the evolution of the synthetic Panthalassa oceanic plates, implementing a Paleozoic reference frame independent of any geodynamic assumptions, and implementing revised models for the Paleozoic evolution of North and South China and the closure of the Rheic Ocean. Paleozoic(410-250 Ma) RMS plate speeds are on average ~8 cm/yr, which is comparable to Mesozoic-Cenozoic rates of ~6 cm/yr on average.Paleozoic global median values of trench migration trend from higher speeds(~2.5 cm/yr) in the late Devonian to rates closer to 0 cm/yr at the end of the Permian(~250 Ma), and during the Mesozoic-Cenozoic(250-0 Ma) generally cluster tightly around ~1.1 cm/yr. Plate motions are best constrained over the past 130 Myr and calculations of global trench convergence rates over this period indicate median rates range between 3.2 cm/yr and 12.4 cm/yr with a present day median rate estimated at~5 cm/yr. For Paleozoic times(410-251 Ma) our model results in median convergence rates largely~5 cm/yr. Globally,~90% of subduction zones modelled in our reconstruction are determined to be in a convergent regime for the period of 120-0 Ma. Over the full span of the model, from 410 Ma to 0 Ma,~93% of subduction zones are calculated to be convergent, and at least 85% of subduction zones are converging for 97% of modelled times. Our changes improve global plate and trench kinematics since the late Paleozoic and our reconstructions of the lowermost mantle structure challenge the proposed fixity of lower mantle structures, suggesting that the eastern margin of the African LLSVP margin has moved by as much as ~1450 km since late Permian times(260 Ma). The model of the plate-mantle system we present suggests that during the Permian Period, South China was proximal to the eastern margin of the African LLSVP and not the western margin of the Pacific LLSVP as previous thought. | Alexander Young Nicolas Flament Kayla Maloney Simon Williams Kara Matthews Sabin Zahirovic R.Dietmar Müller | 2019 | Geoscience Frontiers2019，10，3： | 10 |
| 12 | Computed tomography overestimation of esophageal tumor length: Implications for radiotherapy planning显示文摘AIM:To assess the relationship between preoperative computed tomography(CT)and postoperative pathological measurements of esophageal tumor length and the prognostic significance of CT tumor length data.METHODS:A retrospective study was carried out in 56 patients who underwent curative esophagogastrectomy.Tumor lengths were measured on the immediate preoperative CT and on the post-operative resection specimens.Inter-and intra-observer variations in CT measurements were assessed.Survival data were collected.RESULTS:There was a weak correlation between CT and pathological tumor length(r=0.30,P=0.025).CT lengths were longer than pathological lengths in 68%(38/56)of patients with a mean difference of 1.67 cm(95%CI:1.18-2.97).The mean difference in measurements by two radiologists was 0.39 cm(95% CI:-0.59-1.44).The mean difference between repeat CT measured tumor length(intra-observer variation) were 0.04 cm(95%CI:-0.59-0.66)and 0.47 cm (95%CI:-0.53-1.47).When stratified,patients not receiving neoadjuvant chemotherapy showed a strong correlation between CT and pathological tumor length(r =0.69,P=0.0014,n=37)than patients that did(r= 0.13,P=0.43,n=19).Median survival with CT tumor length>5.6 cm was poorer than with smaller tumors,but the difference was not statistically significant.CONCLUSION:Esophageal tumor length assessed using CT does not reflect pathological tumor extent and should not be the only modality used for management decisions,particularly for planning radiotherapy. | Karim Sillah Luke R Williams Hans-Ulrich Laasch Azeem Saleem Gillian Watkins Susan A Pritchard Patricia M Price Catharine M West Ian M Welch | 2010 | World Journal of Gastrointestinal Oncology2010，2，4： | 10 |
| 13 | 气力输送管道压降预测影响的数值模拟研究显示文摘气力输送管道压降的预测有利于合理设计供风系统。建立了一气力输送实验装置,对某些截面的压力进行了实验测试。运用CFD仿真软件Fluent,建立了3维气固两相湍动双流体压降预测模型,通过对该气力输送系统的水平弯管进行的仿真研究,得到了与实验结果吻合较好的模型,并运用该模型分析了几个主要参数对气力输送系统压降预测的影响。 | 马爱纯 Williams R C 周孑民 Jones M G | 2010 | 武汉理工大学学报2010，32，23： | 9 |
| 14 | Mycophenolate mofetil for drug-induced vanishing bile duct syndrome显示文摘Amoxicillin/clavulanate is associated with liver injury, mostly of a cholestatic pattern. While outcomes are usually benign, progression to cirrhosis and death has been reported. The role of immunosuppressive therapy for patients with a protracted course is unclear. We report the case of an elderly patient who developed prolonged cholestasis secondary to amoxicillin/clavulanate. Vanishing bile duct syndrome was confirmed by sequential liver biopsies. The patient responded to prednisone treatment, but could not be weaned off corticosteroids, even when azathioprine was added. Complete withdrawal of both prednisone and azathioprine was possible by using mycophenolate mofetil, an inosine monophosphate dehydrogenase inhibitor. Sustained remission has been maintained for more than 3 years with low-dose mycophenolate mofetil. | S Simona Jakab A Brian West Dennis M Meighan Robert S Brown Jr William B Hale | 2007 | World Journal of Gastroenterology2007，13，45： | 8 |
| 15 | Resveratrol engages selective apoptotic signals in gastric adenocarcinoma cells显示文摘AIM: To investigate the intracellular apoptotic signals engaged by resveratrol in three gastric adenocarcinoma cancer cell lines, two of which (AGS and SNU-1) express p53 and one (KATO-Ⅲ) with deleted p53. METHODS: Nuclear fragmentation was used to quanti- tate apoptotic cells; caspase activity was determined by photometric detection of cleaved substrates; formation of oxidized cytochrome C was used to measure cytochrome C activity, and Western blot analysis was used to determine protein expression. RESULTS: Gastric cancer cells, irrespective of their p53 status, responded to resveratrol with fragmentation of DNA and cleavage of nuclear lamins A and B and PARP. Resveratrol, however, has no effect on mitochondria-associated apoptotic proteins Bcl-2, Bcl- xl, Bax, Bid or Smac/Diablo, and did not promote sub- cellular redistribution of cytochrome C, indicating that resveratrol-induced apoptosis of gastric carcinoma cells does not require breakdown of mitochondrial membrane integrity. Resveratrol up-regulated p53 protein in SNU-1 and AGS cells but there was a difference in response of intracellular apoptotic signals between these cell lines. SNU-1 cells responded to resveratrol treatment with down-regulation of survivin, whereas in AGS and KATO- Ⅲ cells resveratrol stimulated caspase 3 and cytochrome C oxidase activities. CONCLUSION: These findings indicate that even within a specific cancer the intracellular apoptotic signals engaged by resveratrol are cell type dependent and suggest that such differences may be related to differentiation or lack of differentiation of these cells. | William L Riles Jason Erickson Sanjay Nayyar Mary Jo Atten Bashar M Attar Oksana Holian | 2006 | World Journal of Gastroenterology2006，12，35： | 8 |
| 16 | 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 |
| 17 | Nationwide trends and predictors of inpatient mortality in 83884 transjugular intrahepatic portosystemic shunt显示文摘AIM: To evaluate and validate the national trends and predictors of in-patient mortality of transjugular intrahepatic portosystemic shunt(TIPS) in 15 years.METHODS: Using the National Inpatient Sample which is a part of Health Cost and Utilization Project, we identified a discharge-weighted national estimate of 83884 TIPS procedures performed in the United States from 1998 to 2012 using international classification of diseases-9 procedural code 39.1. The demographic, hospital and co-morbility data were analyzed using a multivariant analysis. Using multi-nominal logistic regression analysis, we determined predictive factors related to increases in-hospital mortality. Comorbidity measures are in accordance to the Comorbidity Software designed by the Agency for Healthcare Research and Quality.RESULTS: Overall, 12.3% of patients died during hospitalization with downward trend in-hospitalmortality with the mean length of stay of 10.8 ± 13.1 d. Notable, African American patients(OR = 1.809 vs Caucasian patients, P < 0.001), transferred patients(OR = 1.347 vs non-transferred, P < 0.001), emergency admissions(OR = 3.032 vs elective cases, P < 0.001), patients in the Northeast region(OR = 1.449 vs West, P < 0.001) had significantly higher odds of inhospital mortality. Number of diagnoses and number of procedures showed positive correlations with in-hospital death(OR = 1.249 per one increase in number of procedures). Patients diagnosed with acute respiratory failure(OR = 8.246), acute kidney failure(OR = 4.359), hepatic encephalopathy(OR = 2.217) and esophageal variceal bleeding(OR = 2.187) were at considerably higher odds of in-hospital death compared with ascites(OR = 0.136, P < 0.001). Comorbidity measures with the highest odds of in-hospital death were fluid and electrolyte disorders(OR = 2.823), coagulopathy(OR = 2.016), and lymphoma(OR = 1.842).CONCLUSION: The overall mortality of the TIPS procedure is steadily decreasing, though the length of stay has remained relatively constant. Specific patient ethnicity, location, transfer status, primary diagnosis and comorbidities correlate with increased odds of TIPS in-hospital death. | Edward Wolfgang Lee Andrew Kuei Sammy Saab Ronald W Busuttil Francisco Durazo Steven-Huy Han Mohamed M El-Kabany Justin P Mc Williams Stephen T Kee | 2016 | World Journal of Gastroenterology2016，22，25： | 7 |
| 18 | 三级高血压单位5100例患者低血钾症与原发性醛固酮增多症的发病率显示文摘常伴有低血钾症的原发性醛固酮增多症(原醛)被认为是一个少见病。广泛筛查高血压患者发现正常血钾的原醛发生率增加。许多研究报道原醛低血钾症的发生率,相反,低血钾症患者中原醛的发生率并不明确。在该回顾性观察研究,研究者探讨了高血压患者中低钾的发生率以及低血钾症合并高血压患者中原醛的发生率。 | 赵狄(译) 刘莉(审校) Burrello J Monticone S Losano I Cavaglià G Buffolo F Tetti M Covella M Rabbia F Veglio F Pasini B Williams TA Mulatero P | 2020 | 中华高血压杂志2020，28，3： | 7 |
| 19 | 2型糖尿病患者采用血管紧张素转换酶抑制剂治疗后血清肌酐急性升高及其继续治疗对主要临床结局的影响显示文摘血管紧张素转换酶抑制剂开始治疗后血清肌酐急性升高≥30%时推荐停药。但血清肌酐升高后继续服药或停药对主要临床结局的长期影响仍不明确。在ADVANCE(糖尿病与血管疾病行动:培哚普利-吲达帕胺与达美康缓释片对照评估)试验中,11 140例糖尿病患者在6周活性导入期后随机采用培哚普利-吲达帕胺或安慰剂治疗。 | Ohkuma T Jun M Rodgers A Cooper ME Glasziou P Hamet P Harrap S Mancia G Marre M Neal B Perkovic V Poulter N Williams B Zoungas S Chalmers J Woodward M 赵狄 练桂丽 | 2019 | 中华高血压杂志2019，27，1： | 6 |
| 20 | Ron receptor-dependent gene regulation of Kupffer cells during endotoxemia显示文摘BACKGROUND: Ron receptor tyrosine kinase signaling in macrophages, including Kupffer cells and alveolar macrophages,suppresses endotoxin-induced proinflammatory cytokine/chemokine production. Further, we have also identified genes from Ron replete and Ron deplete livers that were differentially expressed during the progression of liver inflammation associated with acute liver failure in mice by microarray analyses.While important genes and signaling pathways have been identified downstream of Ron signaling during progression of inflammation by this approach, the precise role that Ron receptor plays in regulating the transcriptional landscape in macrophages, and particular in isolated Kupffer cells, has still not been investigated.METHODS: Kupffer cells were isolated from wild-type(TK+/+)and Ron tyrosine kinase deficient(TK-/-) mice. Ex vivo, the cells were treated with lipopolysaccharide(LPS) in the presence or absence of the Ron ligand, hepatocyte growth factor-like protein(HGFL). Microarray and qRT-PCR analyses were utilized to identify alterations in gene expression between genotypes.RESULTS: Microarray analyses identified genes expressed differentially in TK+/+ and TK-/- Kupffer cells basally as well as after HGFL and LPS treatment. Interestingly, our studies identified Mefv, a gene that codes for the anti-inflammatory protein pyrin, as an HGFL-stimulated Ron-dependent gene.Moreover, lipocalin 2, a proinflammatory gene, which is induced by LPS, was significantly suppressed by HGFL treatment.Microarray results were validated by qRT-PCR studies on Kupffer cells treated with LPS and HGFL.CONCLUSION: The studies herein suggest a novel mechanism whereby HGFL-induced Ron receptor activation promotes the expression of anti-inflammatory genes while inhibiting genes involved in inflammation with a net effect of diminished inflammation in macrophages. | Rishikesh M Kulkarni William D Stuart Susan E Waltz | 2014 | Hepatobiliary & Pancreatic Diseases International2014，13，3： | 6 |
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