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1Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system显示文摘允许的技术内长的基因的特定的规定为基因功能的学习是珍贵的并且在治疗学有大潜力。我们创造了在 CRISPR 上系统,由核酸酶死者 Cas9 (dCas9 ) 蛋白质组成的二部件的 transcriptional 使活跃之物与互补顺序与 transcriptional 激活域和单个指南 RNA (sgRNAs ) 熔化了到基因倡导者。我们证明在 CRISPR 上能高效地以一种悦耳的方式在人和老鼠房间激活外长的记者基因。另外,我们证明在 vivo 的柔韧的记者基因激活能被把系统部件注入老鼠接合子完成。而且,我们证明在 CRISPR 上能激活内长的 IL1RN, SOX2,和 OCT4 基因。最有效的基因激活被对近似倡导者有约束力的 3-4 sgRNAs 的簇完成,建议他们在基因正式就职的 synergistic 行动。显著地,当指向多重基因的 sgRNAs 同时被介绍进房间时,柔韧的多路的内长的基因激活被完成。染色体宽的表示介绍表明了系统的高特性。Albert W Cheng Haoyi Wang Hui Yang Linyu Shi Yarden Katz Thorold W Theunissen Sudharshan Rangarajan Chikdu S Shivalila Daniel B Dadon Rudolf Jaenisch 2013Cell Research2013,23,10:65
2Design of 16S rRNA gene primers for 454 pyrosequencing of the human foregut microbiome显示文摘AIM:To design and validate broad-range 16S rRNA primers for use in high throughput sequencing to classify bacteria isolated from the human foregut microbiome.METHODS:A foregut microbiome dataset was constructed using 16S rRNA gene sequences obtained from oral,esophageal,and gastric microbiomes produced by Sanger sequencing in previous studies represented by 219 bacterial species.Candidate primers evaluated were from the European rRNA database.To assess the effect of sequence length on accuracy of classification,16S rRNA genes of various lengths were created by trimming the full length sequences.Sequences spanning various hypervariable regions were selected to simulate the amplicons that would be obtained using possible primer pairs.The sequences were compared with full length 16S rRNA genes for accuracy in taxonomic classification using online software at the Ribosomal Database Project (RDP).The universality of the primer set was evaluated using the RDP 16S rRNA database which is comprised of 433 306 16S rRNA genes,represented by 36 phyla.RESULTS:Truncation to 100 nucleotides(nt)downstream from the position corresponding to base 28 in the Escherichia coli 16S rRNA gene caused misclassification of 87(39.7%)of the 219 sequences,compared with misclassification of only 29(13.2%)sequences with truncation to 350 nt.Among 350-nt sequence reads within various regions of the 16S rRNA gene,the reverse read of an amplicon generated using the 343F/798R primers had the least(8.2%)effect on classification.In comparison,truncation to 900 nt mimicking single pass Sanger reads misclassified 5.0%of the 219 sequences.The 343F/798R amplicon accurately assigned 91.8%of the 219 sequences at the species level.Weighted by abundance of the species in the esophageal dataset,the 343F/798R amplicon yielded similar classification accuracy without a significant loss in species coverage(92%).Modification of the 343F/798R primers to 347F/803R increased their universality among foregut species.Assuming that a typicalpolymerase chain reaction can tolerate 2 mismatches between a primer and a template,the modified 347F and 803R primers should be able to anneal 98%and 99.6%of all 16S rRNA genes in the RDP database.CONCLUSION:347F/803R is the most suitable pair of primers for classification of foregut 16S rRNA genes but also possess universality suitable for analyses of other complex microbiomes.Carlos W Nossa William E Oberdorf Jφrn A Aas Bruce J Paster Todd Z DeSantis Eoin L Brodie Daniel Malamud Michael A Poles Zhiheng Pei 2010World Journal of Gastroenterology2010,16,33:16
3动力离心模型试验循环剪应力–剪应变反演方法对比显示文摘介绍了基于加速度阵列建立的3种循环剪应力–剪应变反演方法,分析了应用条件和影响因素。基于一组软黏土场地加固动力离心模型试验,探讨了试验加速度记录反演位移的信号处理方法,与多状态下实测位移对比,验证了有效性与可靠性。运用3种反演方法分别求取了两次试验、多种波激励下,自由场地和加固场地内土体剪应力–剪应变动态响应过程。结果表明,在传感器布设间距和采样率满足应用条件下,3种反演方法可获得基本一致结果并反映基本规律,上层土体剪应力小、剪应变大,土体剪切模量与围压密切联系;自由场地剪应变远大于加固场地,并因土体软化呈现强非线性。3种方法对比,三次样条法反演结果准确性对传感器布设间距和采样率较为敏感。王永志 Daniel W Wilson Mohammad Khosravi 袁晓铭 C Guney Olgum 2016岩土工程学报2016,38,2:15
4Role of matrix metalloproteinase,tissue inhibitor of metalloproteinase and tumor necrosis factor-α single nucleotide gene polymorphisms in inflammatory bowel disease显示文摘AIM:To study the (functional) relevance of single nucleotide polymorphisms (SNPs) in genes encoding matrix metalloproteinases (MMP)-1,-2,-3,-9,tissue inhibitors of metalloproteinases (TIMP)-1,-2 and tumor necrosis factor (TNF)-α in the etiopathogenesis of inflammatory bowel diseases (IBD),that may enhance susceptibility and/or disease severity. METHODS:Genomic DNA from 134 Crohn's disease (CD),111 ulcerative colitis (UC) patients and 248 control subjects was isolated from resected intestinal tissue or blood. Allelic composition at SNP loci was determined by PCR-RFLP or tetra primer ARMS PCR. RESULTS:The TIMP-1 genotype TT in women and T in men at SNP +372 T/C was found to increase CD susceptibility (39% vs 23.8%,P=0.018 and 67.9% vs 51.6%,P=0.055,respectively),while women with this genotype were less prone to development of fistulae during follow-up (41.4% vs 68.3%,P=0.025). Male IBD or CD patients carrying the TIMP-1 +372 T-allele expressed lower levels of TIMP-1 in surgically resected macroscopically inflamed tissue (0.065 < P < 0.01). The 5T5T genotype at MMP-3 SNP -1613 5T/6T increased the chance of stenotic complications in CD during follow-up (91.2% vs 71.8%,P = 0.022) but seemed to protect against colonic involvement of this disease at first endoscopic/radiologic examination (35.3% vs 59.5%,P=0.017). CONCLUSION:Allelic composition at the examinedSNPs in genes coding for TIMP-1 and MMP-3 affect CD susceptibility and/or phenotype,i.e.,fistulizing disease,stricture pathogenesis and first disease localisation. These findings reinforce the important role of these proteins in IBD.Martin JW Meijer Marij AC Mieremet-Ooms Ruud A van Hogezand Cornelis BHW Lamers Daniel W Hommes Hein W Verspaget 2007World Journal of Gastroenterology2007,13,21:15
5Inhibition of Mcl-1 enhances cell death induced by the Bcl-2-selective inhibitor ABT-199 in acute myeloid leukemia cells显示文摘Acute myeloid leukemia(AML)is a serious disease.The 5-year survival rates remain frustratingly low(65%for children and 26%for adults).Resistance to frontline chemotherapy(usually cytarabine)often develops;therefore a new treatment modality is needed.Bcl-2 family proteins play an important role in balancing cell survival and apoptosis.The antiapoptotic Bcl-2 family proteins have been found to be dysregulated in AML.ABT-199,a BH3 mimetic,was developed to target antiapoptotic protein Bcl-2.Although ABT-199 has demonstrated promising results,resistance occurs.Previous studies in AML show that ABT-199 alone decreases the association of proapoptotic protein Bim with Bcl-2,but this is compensated by increased association of Bim with prosurvival protein Mcl-1,stabilizing Mcl-1,resulting in resistance to ABT-199.In this study,we investigated the antileukemic activity of the Mcl-1-selective inhibitor A-1210477 in combination with ABT-199 in AML cells.We found that A-1210477 synergistically induced apoptosis with ABT-199 in AML cell lines and primary patient samples.The synergistic induction of apoptosis was decreased upon Bak,Bax and Bim knockdown.While A-1210477 treatment alone also increased Mcl-1 protein levels,combination with ABT-199 reduced binding of Bim to Mcl-1.Our results demonstrate that sequestration of Bim by Mcl-1,a mechanism of ABT-199 resistance,can be abrogated by combined treatment with the Mcl-1 inhibitor A-1201477.Daniel A Luedtke Xiaojia Niu Yihang Pan Jianyun Zhao Shuang Liu Holly Edwards Kang Chen Hai Lin Jeffrey W Taub Yubin Ge 2017Signal Transduction and Targeted Therapy2017,2,1:11
6Potential role of metabolomics in diagnosis and surveillance of gastric cancer显示文摘Gastric cancer is one of the deadliest cancers worldwide, and is especially prevalent in Asian countries. With such high morbidity and mortality, early diagnosis is essential to achieving curative intent treatment and long term survival. Metabolomics is a new field of study that analyzes metabolites from biofluids and tissue samples. While metabolomics is still in its infancy, there are numerous potential applications in oncology, specifically early diagnosis. Only a few studies in the literature have examined metabolomics' role in gastric cancer. Various fatty acid, carbohydrate, nucleic acid, and amino acid metabolites have been identified that distinguish gastric cancer from normal tissue and benign gastric disease. However, findings from these few studies are at times conflicting. Most studies demonstrate some relationship of cancer cells to the Warburg Effect, in that glycolysis predominates with conversion of pyruvate to lactate. This is one of the most consistent findings across the literature. There is less consistency in metabolomic signature with respect to nucleic acids, lipids and amino acids. In spite of this, metabolomics holds some promise for cancer surveillance but further studies are necessary to achieve consistency and validation before it can be widely employed as a clinical tool.Angela W Chan Richdeep S Gill Daniel Schiller Michael B Sawyer 2014World Journal of Gastroenterology2014,20,36:9
7Operative complications and economic outcomes of cholecystectomy for acute cholecystitis显示文摘BACKGROUND Recent management of acute cholecystitis favors same admission(SA)or emergent cholecystectomy based on overall shorter hospital stay and therefore cost savings.We adopted the practice of SA cholecystectomy for the treatment of acute cholecystitis at our tertiary care center and wanted to evaluate the economic benefit of this practice.We hypothesized that the existence of complications,particularly among patients with a higher degree of disease severity,during SA cholecystectomy could negate the cost savings.AIM To compare complication rates and hospital costs between SA vs delayed cholecystectomy among patients admitted emergently for acute cholecystitis.METHODS Under an IRB-approved protocol,complications and charges for were obtained for SA,later after conservative management(Delayed),or elective cholecystectomies over an 8.5-year period.Patients were identified using the acute care surgery registry and billing database.Data was retrieved via EMR,operative logs,and Revenue Cycle Operations.The severity of acute cholecystitis was graded according to the Tokyo Guidelines.TG18 categorizes acute cholecystitis by Grades 1,2,and 3 representing mild,moderate,and severe,respectively.Comparisons were analyzed withχ2,Fisher’s exact test,ANOVA,ttests,and logistic regression;significance was set at P<0.05.RESULTS Four hundred eighty-six(87.7%)underwent a SA while 68 patients(12.3%)received Delayed cholecystectomy.Complication rates were increased after SA compared to Delayed cholecystectomy(18.5%vs 4.4%,P=0.004).The complication rates of patients undergoing delayed cholecystectomy was similar to the rate for elective cholecystectomy(7.4%,P=0.35).Mortality rates were 0.6%vs 0%for SA vs Delayed.Patients with moderate disease(Tokyo 2)suffered more complications among SA while none who were delayed experienced a complication(16.1%vs 0.0%,P<0.001).Total hospital charges for SA cholecystectomy were increased compared to a Delayed approach($44500±$59000 vs$35300±$16700,P=0.019).The relative risk of developing a complication was 4.2x[95%confidence interval(CI):1.4-12.9]in the SA vs Delayed groups.Among eight patients(95%CI:5.0-12.3)with acute cholecystitis undergoing SA cholecystectomy,one patient will suffer a complication.CONCLUSION Patients with Tokyo Grade 2 acute cholecystitis had more complications and increased hospital charges when undergoing SA cholecystectomy.This data supports a selective approach to SA cholecystectomy for acute cholecystitis.Christopher P Rice Krishnamurthy B Vaishnavi Celia Chao Daniel Jupiter August B Schaeffer Whitney R Jenson Lance W Griffin William J Mileski 2019World Journal of Gastroenterology2019,25,48:8
8Gastroenteropancreatic neuroendocrine tumours显示文摘Irvin M Modlin Kjell Oberg Daniel C Chung Robert T Jensen Wouter W de Herder Rajesh V Thakker Martyn Caplin Gianfranco Delle Fave Greg A Kaltsas Eric P Krenning Steven F Moss Ola Nilsson Guido Rindi Ramon Salazar Philippe Ruszniewski Anders Sundin 2008Lancet Oncology2008,,1:8
9Juvenile polyposis syndrome显示文摘Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer.The cumulative life-time risk of colorectal cancer is 39% and the relative risk is 34.Juvenile polyps have a distinctive histology characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands lined by cuboidal to columnar epithelium with reactive changes.Clinically,juvenile polyposis syndrome is defined by the presence of 5 or more juvenile polyps in the colorectum,juvenile polyps throughout the gastrointestinal tract or any number of juvenile polyps and a positive family history of juvenile polyposis.In about 50%-60% of patients diagnosed with juvenile polyposis syndrome a germline mutation in the SMAD4 or BMPR1A gene is found.Both genes play a role in the BMP/TGF-beta signalling pathway.It has been suggested that cancer in juvenile polyposis may develop through the socalled 'landscaper mechanism' where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive carcinoma.Recognition of this rare disorder is important for patients and their families with regard to treatment,follow-up and screening of at risk individuals.Each clinician confronted with the diagnosis of a juvenile polyp should therefore consider the possibility of juvenile polyposis syndrome.In addition,juvenile polyposis syndrome provides a unique model to study colorectal cancer pathogenesis in general and gives insight in the molecular genetic basis of cancer.This review discusses clinical manifestations,genetics,pathogenesis and management of juvenile polyposis syndrome.Lodewijk AA Brosens Danielle Langeveld W Arnout van Hattem Francis M Giardiello G Johan A Offerhaus 2011World Journal of Gastroenterology2011,17,44:7
10Optimizing management of pancreaticopleural fistulas显示文摘AIM:To evaluate the management of pancreaticopleural fistulas involving early endoscopic instrumentation of the pancreatic duct.METHODS:Eight patients with a spontaneous pancre-aticopleural fistula underwent endoscopic retrograde cholang iopancreatography(ERCP) with an intentionto stent the site of a ductal disruption as the primarytreatment. Imaging features and management were evaluated retrospectively and compared with outcome.RESULTS:In one case,the stent bridged the site of aductal disruption. The fistula in this patient closed with in3 wk. The main pancreatic duct in this case appearednormal,except for a leak located in the body of the pancreas. In another patient,the papilla of Vater couldnot be found and cannulation of the pancreatic ductfailed. This patient underwent surgical treatment. In the remaining 6 cases,it was impossible to insert a stentinto the main pancreatic duct properly so as to coverthe site of leakage or traverse a stenosis situated down-stream to the fistula. The placement of the stent failed because intraductal stones(n = 2) and ductal strictures(n = 2) precluded its passage or the stent was too short to reach the fistula located in the distal part of the pancreas(n = 2) . In 3 out of these 6 patients,the pancre-aticopleural fistula closed on further medical treatment.In these cases,the main pancreatic duct was normalor only mildly dilated,and there was a leakage at the body/tail of the pancreas. In one of these 3 patients,additional percutaneous drainage of the peripancre atic fluid collections allowed better control of the leakageand facilitated resolution of the fistula. The remaining3 patients had a tight stenosis of the main pancreatic duct resistible to dilatation and the stent could not beinserted across the stenosis. Subsequent conservative treatment proved unsuccessful in these patients. Aftera failed the rapeutic ERCP,3 patients in our series developed superinfection of the pleural or peripancreatic fluid collections. Four out of 8 patients in our series required subsequent surgery due to a failed non-operative treat-ment. Distal pancreatectomy with splenectomy was performed in 3 cases. In one case,only external drainage of the pancreatic pseudocyst was done because of diffuse peripancreatic inflammatory infiltration precluding safe dissection. There were no perioperative mortalities.There was no recurrence of a pancreati copleural fistulain any of the patients.CONCLUSION:Optimal management of pancreaticopleural fistulas requires appropriate patient selection that should be based on the underlying pancreatic ductab normalities.Marek Wronski Maciej Slodkowski Wlodzimierz Cebulski Daniel Moronczyk Ireneusz W Krasnodebski 2011World Journal of Gastroenterology2011,17,42:6
11儿童期肥胖、成年期肥胖和心血管风险因子显示文摘过去30年,儿童超重或肥胖的发生率明显增加[1]。儿童期肥胖是死亡率增加的预测因子,这主要是由于儿童期肥胖可导致心血管疾病发生率增加。相关的预测研究提示"肥胖流行症"可能改变目前心血管疾病死亡率下降的趋势,使现今儿童的寿命缩短。Juonala M Magnussen CG Berenson GS Venn A Burns TL Sabin MA Srinivasan SR Daniels SR Davis PH Chen W Sun C Cheung M Viikari JS Dwyer T Raitakari OT 叶鹏 2012中华高血压杂志2012,20,1:6
12Multiphase computed tomography radiomics of pancreatic intraductal papillary mucinous neoplasms to predict malignancy显示文摘BACKGROUND Intraductal papillary mucinous neoplasms(IPMNs)are non-invasive pancreatic precursor lesions that can potentially develop into invasive pancreatic ductal adenocarcinoma.Currently,the International Consensus Guidelines(ICG)for IPMNs provides the basis for evaluating suspected IPMNs on computed tomography(CT)imaging.Despite using the ICG,it remains challenging to accurately predict whether IPMNs harbor high grade or invasive disease which would warrant surgical resection.A supplementary quantitative radiological tool,radiomics,may improve diagnostic accuracy of radiological evaluation of IPMNs.We hypothesized that using CT whole lesion radiomics features in conjunction with the ICG could improve the diagnostic accuracy of predicting IPMN histology.AIM To evaluate whole lesion CT radiomic analysis of IPMNs for predicting malignant histology compared to International Consensus Guidelines.METHODS Fifty-one subjects who had pancreatic surgical resection at our institution with histology demonstrating IPMN and available preoperative CT imaging were included in this retrospective cohort.Whole lesion semi-automated segmentation was performed on each preoperative CT using Healthmyne software(Healthmyne,Madison,WI).Thirty-nine relevant radiomic features were extracted from each lesion on each available contrast phase.Univariate analysis of the 39 radiomics features was performed for each contrast phase and values were compared between malignant and benign IPMN groups using logistic regression.Conventional quantitative and qualitative CT measurements were also compared between groups,viaχ2(categorical)and Mann Whitney U(continuous)variables.RESULTS Twenty-nine subjects(15 males,age 71±9 years)with high grade or invasive tumor histology comprised the'malignant'cohort,while 22 subjects(11 males,age 70±7 years)with low grade tumor histology were included in the'benign'cohort.Radiomic analysis showed 18/39 precontrast,19/39 arterial phase,and 21/39 venous phase features differentiated malignant from benign IPMNs(P<0.05).Multivariate analysis including only ICG criteria yielded two significant variables:thickened and enhancing cyst wall and enhancing mural nodule<5 mm with an AUC(95%CI)of 0.817(0.709-0.926).Multivariable post contrast radiomics achieved an AUC(95%CI)of 0.87(0.767-0.974)for a model including arterial phase radiomics features and 0.834(0.716-0.953)for a model including venous phase radiomics features.Combined multivariable model including conventional variables and arterial phase radiomics features achieved an AUC(95%CI)of 0.93(0.85-1.0)with a 5-fold cross validation AUC of 0.90.CONCLUSION Multi-phase CT radiomics evaluation could play a role in improving predictive capability in diagnosing malignancy in IPMNs.Future larger studies may help determine the clinical significance of our findings.Stuart L Polk Jung W Choi Melissa J McGettigan Trevor Rose Abraham Ahmed Jongphil Kim Kun Jiang Yoganand Balagurunathan Jin Qi Paola T Farah Alisha Rathi Jennifer B Permuth Daniel Jeong 2020World Journal of Gastroenterology2020,26,24:5
13Single-nucleotide polymorphisms of matrix metalloproteinases and their inhibitors in gastrointestinal cancer显示文摘Matrix metalloproteinases(MMPs) are implicated in cancer development and progression and are associated with prognosis.Single-nucleotide polymorphisms(SNPs) of MMPs,most frequently located in the promoter region of the genes,have been shown to influence cancer susceptibility and/or progression.SNPs of MMP-1,-2,-3,-7,-8,-9,-12,-13 and-21 and of the tissue inhibitor of metalloproteinases(TIMPs) TIMP-1 and TIMP-2 have been studied in digestive tract tumors.The contribution of these polymorphisms to the cancer risk and prognosis of gastrointestinal tumors are reviewed in this paper.Alexandra MJ Langers Hein W Verspaget Daniel W Hommes Cornelis FM Sier 2011World Journal of Gastrointestinal Oncology2011,3,6:4
14On tolerability and safety of a maintenance treatment with 6-thioguanine in azathioprineor 6-mercaptopurine intolerant IBD patients显示文摘AIM: To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment period of at least 1 year.METHODS: Database analysis.RESULTS: Twenty out of ninety-five (21%) patients discontinued 6-TG (mean dose 24.6 mg; mean 6-TGN level 540 pmol/8×108 RBC) within 1 year. Reasons for discontinuation were GI complaints (31%), malaise (15%)and hepatotoxicity (15%). Hematological events occurred in three patients, one discontinued treatment. In the 6-TG-tolerant group, 9% (7/75) could be classified as hepatotoxicity. An abdominal ultrasound was performed in 54% of patients, one patient had splenomegaly.CONCLUSION: The majority of AZA or 6-MP-intolerant IBD patients (79%) is able to tolerate maintenance treatment with 6-TG (dosages between 0.3 and 0.4 mg/kg per d). 6-TG may still be considered as an escape maintenance immunosuppressant in this difficult to treat group of patients, taking into account potential toxicity and efficacy of other alternatives. The recently reported hepatotoxicity is worrisome and 6-TG should therefore be administered only in prospective trials.Nanne KH de Boer Luc JJ Derijks Lennard PL Gilissen Daniel W Hommes Leopold GJB Engels Sybrand Y de Boer Gijsbertus den Hartog Piet M Hooymans Anja BU M(?)kelburg Barend D Westerveld Anton HJ Naber Chris JJ Mulder Dirk J de Jong 2005World Journal of Gastroenterology2005,11,35:4
15Gene and cell therapy based treatment strategies for inflammatory bowel diseases显示文摘Inflammatory bowel diseases(IBD)are a group of chronic inflammatory disorders most commonly affecting young adults.Currently available therapies can result in induction and maintenance of remission,but are not curative and have sometimes important side effects.Advances in basic research in IBD have provided new therapeutic opportunities to target the inflammatory process involved.Gene and cell therapy approaches are suitable to prevent inflammation in the gastrointestinal tract and show therefore potential in the treatment of IBD.In this review,we present the current progress in the field of both gene and cell therapy and future prospects in the context of IBD.Regarding gene therapy,we focus on viral vectors and their applications in preclinical models.The focus for cell therapy is on regulatory T lymphocytes and mesenchymal stromal cells,their potential for the treatment of IBD and the progress made in both preclinical models and clinical trials.Sander van der Marel Anna Majowicz Sander van Deventer Harald Petry Daniel W Hommes Valerie Ferreira 2011World Journal of Gastrointestinal Pathophysiology2011,2,6:3
16Langerhans cell histiocytosis masquerading as acute appendicitis: Case report and review显示文摘Langerhans cell histiocytosis(LCH) is a rare syndrome characterized by unifocal,multifocal unisystem,or disseminated/multi-system disease that commonly involves the bone,skin,lymph nodes,pituitary,or sometimes lung(almost exclusively in smokers) causing a variety of symptoms from rashes and bone lesions to diabetes insipidus or pulmonary infiltrates.We present a previously unreported case of gastrointestinal LCH as well as a novel characteristic lesion affecting the colon of a young woman who presented with signs and symptoms mimicking acute on chronic appendicitis.Immunohistochemical analysis of appendectomy specimen and nodular specimens on colonoscopy demonstrated S-100,CD1a,and langerin reactivity.The patient underwent systemic chemotherapy with cytarabine and demonstrated excellent response to therapy.Mohammad M Karimzada Michele N Matthews Samuel W French Daniel De Ugarte Dennis Y Kim 2017World Journal of Gastrointestinal Endoscopy2017,9,3:3
17Pyruvate-fortified resuscitation stabilizes cardiac electrical activity and energy metabolism during hypovolemia显示文摘AIM: To test the hypothesis that fluid resuscitation with Ringer's solution enriched with pyruvate(PR), a physiological antioxidant and energy substrate, affords protection of myocardial metabolism and electrophysiological performance superior to lactated Ringer's(LR) during hypovolemia and hindlimb ischemia-reperfusion.METHODS: Male domestic goats(25-30 kg) were exsanguinated to a mean arterial pressure of 48 ± 1 mm Hg. Right hindlimb ischemia was imposed for 90 min by applying a tourniquet and femoral crossclamp. LR or PR, infused iv, delivered 0.05 mmol/kg per minute L-lactate or pyruvate, respectively, from 30 min hindlimb ischemia until 30 min post-ischemia. Time controls(TC) underwent neither hemorrhage, hindlimb ischemia nor resuscitation. Goats were sacrificed and left ventricular myocardium biopsied at 90 min fluid resuscitation(n = 6 per group) or 3.5 h later(n = 9 LR, 10 PR, 8 TC).RESULTS: Myocardial 8-isoprostane content, phosphocreatine phosphorylation potential, creatine kinase activity, and heart rate-adjusted QT interval(QTc) vari- ability were evaluated at 90 min resuscitation and 3.5 h post-resuscitation. PR sharply lowered pro-arrhythmic QTc variability vs LR(P < 0.05); this effect persisted 3.5 h post-resuscitation. PR lowered myocardial 8-isoprostane content, a product of oxidative stress, by 39 and 37% during and 3.5 h after resuscitation, respectively, vs LR. Creatine kinase activity fell 42% post-LR vs TC(P < 0.05), but was stable post-PR(P < 0.02 vs post-LR). PR doubled phosphocreatine phosphorylation potential, a measure of ATP free energy state, vs TC and LR(P < 0.05); this energetic enhancement persisted 3.5 h post-resuscitation.CONCLUSION: By augmenting myocardial energy state and protecting creatine kinase activity, pyruvateenriched resuscitation stabilized cardiac electrical function during central hypovolemia and hindlimb ischemiareperfusion.Hunaid A Gurji Daniel W White Besim Hoxha Jie Sun Albert H Olivencia-Yurvati Robert T Mallet 2013World Journal of Critical Care Medicine2013,2,4:3
18Ron receptor-dependent gene regulation in a mouse model of endotoxin-induced acute liver failure显示文摘BACKGROUND:Prior experimentation has shown that loss of the tyrosine kinase(TK) signaling domain of the Ron receptor leads to marked hepatocyte protection in a model of lipopolysaccharideinduced acute liver failure(ALF) in D-galactosamine(GalN)sensitized mice.The aim of this study was to identify the role of Ron in the regulation of hepatic gene expression.METHODS:Microarray analyses were performed on liver RNA isolated sequentially from wild-type(WT) and TK-/mice during the progression of ALF.Gene array data were validated using Western and immunohistochemistry analyses as well as with ex vivo culture systems.RESULTS:At baseline,101 genes were differentially expressed between WT and TK-/-livers,which regulate processes involved in hypoxia,proliferation,apoptosis and metabolism.One hour after ALF induction,WT livers exhibited increased cytokine expression compared to TK-/-livers,and after 4 hours,an induction of suppressor of cytokine signaling(SOCS) genes as well as JAK-STAT pathway activation were prominent in TK-/livers compared to controls.CONCLUSION:Our studies suggest a novel hepato-protective mechanism in Ron TK-/-mice wherein increased and sustained SOCS production and JAK-STAT activation in the hepatocyte may inhibit the destructive proinflammatory milieu and promote survival factors which blunt hepatic death and the ensuing development of ALF.Rishikesh M Kulkarni Louis W Kutcher William D Stuart Daniel J Carson Mike A Leonis Susan E Waltz 2012Hepatobiliary & Pancreatic Diseases International2012,11,4:3
19Comprehensive lifestyle intervention vs soy protein-based meal regimen in non-alcoholic steatohepatitis显示文摘BACKGROUND Non-alcoholic steatohepatitis(NASH) has become one of the leading causes of liver disease in the western world. In obese patients weight reduction is recommended. Up to now there are no specific guidelines for weight loss in order to reduce hepatic fat content.AIM To investigate the effects of a 24-wk guided lifestyle intervention program compared to a meal replacement regimen based on soy protein.METHODS Twenty-six subjects with NASH participated in a randomized single-center study. They were randomly assigned to either meal replacement group(MR-G)with soy-yogurt-honey preparation or to guided lifestyle change group(LC-G)with endurance activity and nutrition counselling. Serum alanine transaminase(ALT), aspartate transaminase(AST), lipid parameters, and adipokines were measured. Liver fat content and lipid composition were determined by magnetic resonance imaging and magnetic resonance spectroscopy. Body fat mass and lean body mass were assessed using Bod Pod? device. Pre-and post-intervention monitoring of parameters was performed. Statistical analyses were conducted with SPSS software, results were expressed as median(interquartile range).RESULTS Twenty-two subjects(MR-G, n = 11 and LC-G, n = 11) completed the study(9 women, 13 men; age 52.1(15.0) years, body mass index(BMI) 32.3(3.3) kg/m^2).In both groups a significant weight loss was achieved(MR-G:-6.4(3.6) kg, P <0.01; LC-G:-9.1(10.4) kg, P < 0.01). BMI dropped in both groups(MR-G:-2.3(1.5)kg/m^2, P = 0.003; LC-G:-3.0(3.4) kg/m^2, P = 0.006). Internal fat and hepatic lipid content were markedly reduced in both groups in comparable amount. There was a strong correlation between reduction in liver fat and decrease in ALT.Likewise, both groups showed an improvement in glycemic control and lipid profile. Changes in adipokines, particularly in adiponectin and leptin were closely related to intrahepatic lipid changes.CONCLUSION Comprehensive lifestyle intervention and meal replacement regimen have comparable effects on body and liver fat, as well as decrease in markers of hepatic inflammation among NASH patients.Peter Deibert Adhara Lazaro Denise Schaffner Aloys Berg Daniel Koenig Wolfgang Kreisel Manfred W Baumstark Daniel Steinmann Martin Buechert Thomas Lange 2019World Journal of Gastroenterology2019,25,9:3
20Management of opioid side effects in cancer-related and chronic noncancer pain: a systematic review显示文摘Ewan McNicol Nathalie Horowicz-Mehler Ruth A Fisk Kyle Bennett Maria Gialeli-Goudas Priscilla W Chew Joseph Lau Daniel Carr 2003Journal of Pain2003,,5:3
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