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1Intracellular HMGB1 as a novel tumor suppressor of pancreatic cancer显示文摘尽管有最近的进展, oncogenic K 地岬驾驶的胰腺的 ductal 腺癌(PDAC ) 在最致命的人的癌症之中留在现代医学。PDAC 的致病对内在的染色体不稳定性和外来的发炎激活部分可归因。然而,在在胰腺的 tumorigenesis 的这二个事件之间的分子的连接充分还没被建立了。这里,我们证明(HMGB1 ) 细胞内部的高活动性组盒子 1 显著地压制 oncogenic 由禁止染色体的 K-Ras-driven 胰腺的 tumorigenesis 调停不稳定性的支持 inflammatory nucleosome 版本。任何一个单身者的有条件的基因脱离或在胰的 HMGB1 的两等位基因在出生使老鼠变为极其敏感到先锋损害的 oncogenic K-Ras-driven 开始,包括胰腺的 intraepithelial 瘤, intraductal 乳突的 mucinous 瘤,和 mucinous 膀胱的瘤。在胰的 HMGB1 的损失与染色体重新整理和 telomere 畸形描绘的氧化 DNA 损坏和 chromosomal 不稳定性被联系。这些导致煽动性的 nucleosome 版本并且宣传 K-Ras-driven 胰腺的 tumorigenesis。细胞外的 nucleosomes 支持 interleukin 6 (IL-6 ) 由渗入 macrophages/neutrophils 的分泌物并且提高在胰腺的损害表明激活的 oncogenic K 地岬。到 IL-6 或 histone H3 或为先进 glycation 的受体的大美人的抵销的抗体结束产品都限制表明激活的 K 地岬,阻止癌症开发和转移 / 侵略,并且延长在 Pdx1-Cre 的动物幸存; K 地岬 G12D/+;Hmgb1/ 鼠标。由 glycyrrhizin 的 HMGB1 损失的药理学抑制在煽动性的条件下面在老鼠限制 oncogenic K-Ras-driven tumorigenesis。减少在 PDAC 病人的 HMGB1 的原子、全部的细胞的表示与差的全面幸存相关,在 PDAC 与预示、治疗学的关联作为新奇肿瘤 suppressor 支持细胞内部的 HMGB1。Rui Kang Yangchun Xie Qiuhong Zhang Wen Hou Qingping Jiang Shan Zhu Jinbao Liu Dexing Zeng Haichao Wang David L Bartlet Timothy R Billiar Herbert J Zeh III Michael T Lotze Daolin Tang 2017Cell Research2017,27,7:22
2Diagnostic accuracy of endoscopic ultrasound in pancreatic neuroendocrine tumors: A systematic review and meta analysis显示文摘AIM: To detect pancreatic neuroendocrine tumors (PNETs) has been varied. This study is undertaken to evaluate the accuracy of endoscopic ultrasound (EUS) in detecting PNETs.METHODS: Only EUS studies confirmed by surgery or appropriate follow-up were selected. Articles were searched in Medline, Ovid journals, Medline nonindexed citations, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. Pooling was conducted by both fixed and random effects model). RESULTS: Initial search identified 2610 reference articles, of these 140 relevant articles were selected and reviewed. Data was extracted from 13 studies (n = 456) which met the inclusion criteria. Pooled sensitivity of EUS in detecting a PNETs was 87.2% (95%CI: 82.2-91.2). EUS had a pooled specificity of 98.0% (95%CI: 94.3-99.6). The positive likelihood ratio of EUS was 11.1 (95%CI: 5.34-22.8) and negative likelihood ratio was 0.17 (95%CI: 0.13-0.24). The diagnostic odds ratio, the odds of having anatomic PNETs in positive as compared to negative EUS studies was 94.7 (95%CI: 37.9-236.1). Begg-Mazumdar bias indicator for publication bias gave a Kendall's tau value of 0.31 (P = 0.16), indication no publication bias. The P for χ2 heterogeneity for all the pooled accuracy estimates was > 0.10. CONCLUSION: EUS has excellent sensitivity and specificity to detect PNETs. EUS should be strongly considered for evaluation of PNETs.Srinivas R Puli Nikhil Kalva Matthew L Bechtold Smitha R Pamulaparthy Micheal D Cashman Norman C Estes Richard H Pearl Fritz-Henry Volmar Sonu Dillon Michael F Shekleton David Forcione 2013World Journal of Gastroenterology2013,19,23:14
3High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes显示文摘Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening(HTS) data for 3 762 distinct global gene knockout(KO) mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type(WT) cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging,ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass: 23 previously reported genes(Calcr, Cebpb, Crtap, Dcstamp, Dkk1, Duoxa2, Enpp1, Fgf23, Kiss1/Kiss1 r, Kl(Klotho),Lrp5, Mstn, Neo1, Npr2, Ostm1, Postn, Sfrp4, Slc30a5, Slc39a13, Sost, Sumf1, Src, Wnt10b), five novel genes extensively characterized(Cldn18, Fam20 c, Lrrk1, Sgpl1, Wnt16), five novel genes with preliminary characterization(Agpat2, Rassf5, Slc10a7, Slc26a7, Slc30a10) and three novel undisclosed genes coding for potential osteoporosis drug targets.Robert Brommage Jeff Liu Gwenn M Hansen Laura L Kirkpatrick David G Potter Arthur T Ss Brian Zambrowicz David R Powell Peter Vogel 2014Bone Research2014,2,3:7
4Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach: Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)显示文摘Inzucchi Silvio E Bergenstal Richard M Buse John B Diamant Michaela Ferrannini Ele Nauck Michael Peters Anne L Tsapas Apostolos Wender Richard Matthews David R 2012EN2012,,3:6
5Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales显示文摘C.P Wilkinson Frederick L Ferris Ronald E Klein Paul P Lee Carl David Agardh Matthew Davis Diana Dills Anselm Kampik R Pararajasegaram Juan T Verdaguer 2003Ophthalmology2003,,9:4
6FK506对实验性卒中疗效的系统评价和Meta分析显示文摘FK506是治疗急性卒中的一种候选用药。决定一种药物是否可以用于临床试验,应当以全面的、无偏倚的动物实验数据的评估为依据,同时还应考虑到这些数据的局限性。这种评估不但应包括药物疗效,而且也应包括药效在体内的特征和局限性。本研究应用系统评价和Meta分析的方法对FK506在卒中动物模型中保护作用的证据进行评价。总共纳入了29个描述了实验步骤的研究,包括1759只动物。结果显示,FK506疗效的点估计值(结局指标的改善)是31.3%[95%CI(0.272-0.354)]。在采用氯胺酮麻醉和短暂性脑缺血的动物实验中,FK506的疗效更高,在使用大鼠,合并其他疾病的动物及仅以梗死面积为疗效指标的实验中,FK506疗效较低。已发表的实验研究质量均接近临床试验标准,但在高质量的研究中,FK506的疗效较低。FK506在实验性脑卒中的研究中,虽然显示出有明显的疗效,但是应注意由于研究质量和可能的发表偏倚等冈素的影响,FK506的疗效可能被过高估计。Malcolm R Macleod Tori O’Collins Laura L Horky David W Howells Geoffrey A Donnan 段建钢 2006中国循证医学杂志2006,6,6:3
7Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial显示文摘David N Krag Stewart J Anderson Thomas B Julian Ann M Brown Seth P Harlow Joseph P Costantino Takamaru Ashikaga Donald L Weaver Eleftherios P Mamounas Lynne M Jalovec Thomas G Frazier R Dirk Noyes André Robidoux Hugh MC Scarth Norman Wolmark 2010Lancet Oncology2010,,10:3
8Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source显示文摘BACKGROUND The trans-fat containing AMLN(amylin liver non-alcoholic steatohepatitis,NASH)diet has been extensively validated in C57BL/6J mice with or without the Lep^ob/Lep^ob(ob/ob)mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH.Due to a recent ban on trans-fats as food additive,there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57BL/6J mice.AIM To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat.METHODS Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-fat(Primex shortening)substituted by equivalent amounts of palm oil[Gubra amylin NASH,(GAN)diet]for 8,12 and 16 wk.C57BL/6J mice were fed the same diets for 28 wk.AMLN and GAN diets had similar caloric content(40%fat kcal),fructose(22%)and cholesterol(2%)level.RESULTS The GAN diet was more obesogenic compared to the AMLN diet and impaired glucose tolerance.Biopsy-confirmed steatosis,lobular inflammation,hepatocyte ballooning,fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMLN diet.C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets.CONCLUSION Substitution of Primex with palm oil promotes a similar phenotype of biopsyconfirmed NASH in ob/ob and C57BL/6J mice,making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments.Michelle L Boland Denise Oro Kirstine S T■lb■l Sebastian T Thrane Jens Christian Nielsen Taylor S Cohen David E Tabor Fiona Fernandes Andrey Tovchigrechko Sanne S Veidal Paul Warrener Bret R Sellman Jacob Jelsing Michael Feigh Niels Vrang James L Trevaskis Henrik H Hansen 2019World Journal of Gastroenterology2019,25,33:3
9Is There a Possibility of a Cure in Patients With Colorectal Peritoneal Carcinomatosis Amenable to Complete Cytoreductive Surgery and Intraperitoneal Chemotherapy?显示文摘Diane Goéré David Malka Dimitri Tzanis Vinicius Gava Valérie Boige Clarisse Eveno Léon Maggiori Frédéric Dumont Michel Ducreux Dominique Elias 2013Annals of Surgery2013,,6:2
10Age at diagnosis of type 2 diabetes and cardiovascular risk factor profile:A pooled analysis显示文摘BACKGROUND The diagnosis of type 2 diabetes(T2D)in younger adults,an increasingly common public health issue,is associated with a higher risk of cardiovascular complications and mortality,which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age.AIM To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with T2D.METHODS A pooled dataset was used,comprised of data from five previous studies of adults with T2D,including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 years.Anthropometric and blood biomarker measurements included body weight,body mass index(BMI),waist circumference,body fat percentage,glycaemic control(HbA1c),lipid profile and blood pressure.Univariable and multivariable linear regression models,adjusted for diabetes duration,sex,ethnicity and smoking status,were used to investigate the association between age at diagnosis and each cardiovascular risk factor.RESULTS A higher proportion of participants diagnosed with T2D under the age of 40 were female,current smokers and treated with glucose-lowering medications,compared to participants diagnosed later in life.Participants diagnosed with T2D under the age of 40 also had higher body weight,BMI,waist circumference and body fat percentage,in addition to a more adverse lipid profile,compared to participants diagnosed at an older age.Modelling results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight[95%confidence interval(CI):0.52-0.82 kg],0.18 kg/m^(2) higher BMI(95%CI:0.10-0.25)and 0.32 cm higher waist circumference(95%CI:0.14-0.49),after adjustment for duration of diabetes and other confounders.Younger age at diagnosis was also significantly associated with higher HbA1c,total cholesterol,low-density lipoprotein cholesterol and triglycerides.CONCLUSION The diagnosis of T2D earlier in life is associated with a worse cardiovascular risk factor profile,compared to those diagnosed later in life.Mary M Barker Francesco Zaccardi Emer M Brady Gaurav S Gulsin Andrew P Hall Joseph Henson Zin ZinHtike Kamlesh Khunti Gerald P McCann Emma L Redman David R Webb Emma G Wilmot Tom Yates Jian Yeo Melanie J Davies Jack A Sargeant 2022World Journal of Diabetes2022,13,3:2
11Where is the global in global mental health?A call for inclusive multicultural collaboration显示文摘To the editor:Common mental health disorders,like depression and anxiety,account for 45%of the global disease burden on youths aged 15-29.1 This challenge is particularly significant in low and middle-income countries(LMICs)where risk factors such as poverty,limited treatment options and stigma restrict access to care and exacerbate the burden and magnify the impact of mental disorders.23 Given these barriers,there is an urgent need for research dedicated to expanding mental healthcare for young people in LMICs.Tom L Osborn Akash R Wasil John R Weisz Arthur Kleinman David M Ndetei 2020General Psychiatry2020,33,6:2
12Endoscopic ultrasound-guided fiducial marker placement in pancreatic cancer:A systematic review and meta-analysis显示文摘BACKGROUND Pancreatic cancer(PC)mortality remains high despite advances in therapy.Combination chemoradiotherapy offers modest survival benefit over monotherapy with either.Fiducial markers serve as needed landmarks for imageguided radiotherapy(IGRT).Traditionally,these markers were placed surgically or percutaneously with limitations of each.Endoscopic ultrasound-guided placement overcomes these limitations.AIM To evaluate the safety,efficacy,and feasibility of endoscopic ultrasound(EUS)-guided fiducial placement for PC undergoing IGRT.METHODS Articles were searched in MEDLINE,PubMed,and Ovid journals.Pooling was conducted by fixed and random effects models.Heterogeneity was assessed using Cochran’s Q test based upon inverse variance weights.RESULTS Initial search identified 1024 reference articles for EUS-guided fiducial placement in PC.Of these,261 relevant articles were reviewed.Data was extracted from 11 studies(n=820)meeting inclusion criteria.Pooled proportion of successful placement was 96.27%(95%CI:95.35-97.81)with fiducial migration rates low at 4.33%(95%CI:2.45-6.71).Adverse event rates remained low,with overall pooled proportion of 4.85%(95%CI:3.04-7.03).CONCLUSION EUS-guided placement of fiducial markers for IGRT of PC is safe,feasible,and efficacious.The ability to target deep structures under direct visualization while remaining minimally invasive are added benefits.Moreover,the ability to perform fine needle aspiration or celiac plexus neurolysis add value and increase patient-care efficiency.Whether EUS-guided fiducial placement improves outcomes in IGRT or offers any mortality benefits over traditional placement remains unknown and future studies are needed.Jaymon B Patel Vakya Revanur David G Forcione Matthew L Bechtold Srinivas R Puli 2020World Journal of Gastrointestinal Endoscopy2020,12,8:2
13Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales显示文摘C.P Wilkinson Frederick L Ferris Ronald E Klein Paul P Lee Carl David Agardh Matthew Davis Diana Dills Anselm Kampik R Pararajasegaram Juan T Verdaguer 2003Ophthalmology2003,,9:2
14Increasing diabetes self-management education in community settings显示文摘Susan L Norris Phyllis J Nichols Carl J Caspersen Russell E Glasgow Michael M Engelgau Leonard Jack Susan R Snyder Vilma G Carande-Kulis George Isham Sanford Garfield Peter Briss David McCulloch 2002American Journal of Preventive Medicine2002,,4:2
15Lymphoepithelial cysts and cystic lymphangiomas: Underrecognized benign cystic lesions of the pancreas显示文摘AIM: To identify their diagnostic and prognostic clinical characteristics in a large series.METHODS: Retrospective review of clinicopathologic and imaging characteristics of patients diagnosed with lymphoepithelial cysts and cystic lymphangiomas of the pancreas at Massachusetts General Hospital.RESULTS: Twelve patients were identified between 1/1/1997 and 8/1/2007. Their median age was 55.5 years(range 19-78 years), and 6 were females. The le-sion was incidentally discovered in half of the patients.Contrast enhanced computed tomography demonstrat-ed that the cysts had thin walls, without calcifications, pancreatic duct dilation or pancreatic parenchyma inva-sion. Endoscopic ultrasound with fine needle aspiration(EUS/FNA) confirmed the diagnosis of a lymphoepithe-lial cyst in 3 patients, one of whom was spared an op-eration and continues to do well after 6 years. Eleven patients had a resection: 3 pancreaticoduodenecto-mies, 7 distal pancreatectomies, and 1 enucleation. The median size of the cysts was 3 cm(range 2-20 cm). At a median follow-up of 57 mo no recurrences or other pancreas-related conditions occurred.CONCLUSION: Lymphoepithelial cysts and cystic lymphangiomas of the pancreas can be diagnosed with a combination of contrast-enhanced computed tomog-raphy scans and EUS/FNA. If the lesion is asymptom-atic, an operation might be avoided.Ioannis T Konstantinidis Avinash Kambadakone Onofrio A Catalano Dushyant V Sahani Vikram Deshpe David G Forcione Jennifer A Wargo Carlos Fernandez-del Castillo Keith D Lillemoe Andrew L Warshaw Cristina R Ferrone 2014World Journal of Gastrointestinal Surgery2014,6,7:2
16Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study显示文摘Julia Granerod Helen E Ambrose Nicholas WS Davies Jonathan P Clewley Amanda L Walsh Dilys Morgan Richard Cunningham Mark Zuckerman Ken J Mutton Tom Solomon Katherine N Ward Michael PT Lunn Sarosh R Irani Angela Vincent David WG Brown Natasha S Crowcroft 2010The Lancet Infectious Diseases2010,,12:2
17Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial显示文摘David N Krag Stewart J Anderson Thomas B Julian Ann M Brown Seth P Harlow Takamaru Ashikaga Donald L Weaver Barbara J Miller Lynne M Jalovec Thomas G Frazier R Dirk Noyes André Robidoux Hugh MC Scarth Denise M Mammolito David R McCready Eleftherios P Mamo 2007Lancet Oncology2007,,10:2
18Soil moisture: A central and unifying theme in physical geography显示文摘Legates David R Mahmood Rezaul Levia Delphis F DeLiberty Tracy L Quiring Steven M Houser Chris Nelson Frederick E 2011Progress in Physical Geography2011,,1:2
19Synthesis and evaluation of advanced nanocrystalline tungsten-based materials显示文摘 David L B 1999P/M Science and Technology Brief1999,1,1:1
20The carbon we do not see-the impact of low molecular weight compounds on carbon dynamics and respiration in forest soils:a review显示文摘PATRICK A W DAVID L J FINLAY R 2005Soil Biology & Biochemistry2005,37,:1
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