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| 1 | Lipoprotein-associated phospholipase A2 prognostic role in atherosclerotic complications显示文摘Atherosclerosis manifests itself clinically at advanced stages when plaques undergo hemorrhage and/or rupture with superimposed thrombosis, thus abruptly stopping blood supply. Identification of markers of plaque destabilization at a pre-clinical stage is, therefore, a major goal of cardiovascular research. Promising results along this line were provided by studies investigating the lipoprotein-associated phospholipase A2(Lp-PLA2), a member of phospholipase A2 proteins family that plays a key role in the metabolism of pro-inflammatory phospholipids, as oxidized low-density lipoproteins, and in the generation of pro-atherogenic metabolites, including lysophosphatidylcholine and oxidized free fatty acids. We herein review the experimental and clinical studies supporting use of Lp-PLA2 activity for predicting cardiovascular events. To his end we considered not only Lp-PLA2 activity and mass, but also Lp-PLA2 gene variations and their association with incident coronary artery disease, stroke, and cardiovascular mortality. Based on these evidences the major scientific societies have included in their guidelines the measurement of Lp-PLA2 activity among the biomarkers that are useful in risk stratification of adult asymptomatic patients at intermediate cardiovascular risk. The results of two recently published major clinical trials with the LpPLA2 inhibitor darapladib, which seem to challenge the pathogenic role of Lp-PLA2, will also be discussed. | Giuseppe Maiolino Valeria Bisogni Giacomo Rossitto Gian Paolo Rossi | 2015 | World Journal of Cardiology2015，7，10： | 66 |
| 2 | Platelet-to-lymphocyte ratio in the setting of liver transplantation for hepatocellular cancer: A systematic review and meta-analysis显示文摘AIM To perform a systematic review and meta-analysis on platelet-to-lymphocyte ratio(PLR) as a risk factor for post-transplant hepatocellular cancer(HCC) recurrence. METHODS A systematic literature search was performed using PubM ed. Participants of any age and sex, who underwent liver transplantation for HCC were considered following these criteria:(1) studies comparing pre-transplant low vs high PLR values;(2) studies reporting post-transplant recurrence rates; and(3) if more than one study was reported by the same institute, only the most recent was included. The primary outcome measure was set for HCC recurrence after transplantation. RESULTS A total of 5 articles, published between 2014 and 2017, fulfilled the selection criteria. As for the quality of the reported studies, all the investigated articles presented an overall high quality. A total of 899 cases were investigated: 718 cases(80.0%) were males. Three studies coming from European countries and one from Japan presented HCV as the main cause of cirrhosis. On the opposite, one Chinese study presented a greater incidence of HBV-related cirrhotic cases. In all the studies apart one, the PLR cut-off value of 150 was reported. At meta-analysis, high PLR value was associated with a significant increase in recurrence after transplantation(OR = 3.33; 95%CI: 1.78-6.25; P < 0.001). A moderate heterogeneity was observed among the identified studies according to the Higgins I^2 statistic value.CONCLUSION Pre-transplant high PLR values are connected with an increased risk of post-operative recurrence of hepatocellular cancer. More studies are needed for better clarify the biological mechanisms of this results. | Quirino Lai Fabio Melandro Zoe Larghi Laureiro Francesco Giovanardi Stefano Ginanni Corradini Flaminia Ferri Redan Hassan Massimo Rossi Gianluca Mennini | 2018 | World Journal of Gastroenterology2018，24，15： | 19 |
| 3 | Critical minimum temperature limits xylogenesis and maintains treelines on the southeastern Tibetan Plateau显示文摘Physiological and ecological mechanisms that define treelines are still debated.It has been suggested that the absence of trees above the treeline is caused by low temperatures that limit growth.Thus,we hypothesized that there is a critical minimum temperature(CTmin) preventing xylogenesis at treeline.We tested this hypothesis by examining weekly xylogenesis across three and four growing seasons in two natural Smith fir(Abies georgei var.smithii) treeline sites on the southeastern Tibetan Plateau.Despite differences in the timing of cell differentiation among years,minimum air temperature was the dominant climatic variable associated with xylem growth;the critical minimum temperature(CTmin) for the onset and end of xylogenesis occurred at 0.7 ± 0.4 °C.A process-based modelling chronology of tree-ring formation using this CTminwas consistent with actual tree-ring data.This extremely low CTminpermits Smith fir growing at treeline to complete annual xylem production and maturation and provides both support and a mechanism for treeline formation. | Xiaoxia Li Eryuan Liang Jozica Gricar Sergio Rossi Katarina Cufar Aaron M. Ellison | 2017 | Science Bulletin2017，62，11： | 17 |
| 4 | Aquaporin-4: orthogonal array assembly, CNS functions, and role in neuromyelitis optica显示文摘Aquaporin-4 (AQP4 ) 是在整个中央神经系统在星形细胞,以及在肾,肺,胃和骨胳的肌肉表示的水选择的 transporter。二 AQP4 isoforms 由其他的 spicing, M1 和 M23 AQP4 生产了,形式 heterotetramers 在称为粒子(OAP ) 的直角的数组的超分子的结构集合在房间血浆膜。AQP4 空的老鼠的显型分析在大脑和针的绳索水显示 AQP4 的参与平衡,星形细胞迁居,神经信号 transduction 和 neuroinflammation。AQP4 空的老鼠表明减少的大脑在细胞毒素的服的浮肿,但是增加的大脑在 vasogenic 浮肿和脑水肿胀大胀大。AQP4 缺乏也增加抓住持续时间,损害 glial 结疤,并且减少自体免疫的 neuroinflammation 的严厉。每这些显型根据在 AQP4 缺乏的减少的星形细胞水渗透是多半可解释的。AQP4 也涉及 neuroinflammatory demyelinating 疾病 neuromyelitis optica (NMO ) ,在指向 AQP4 的自身抗体(NMO-IgG ) 生产星形细胞损坏和发炎的地方。管理 NMO-IgG 和人由 intracerebral 注射补充的老鼠与 neuroinflammation, demyelination, perivascular 补充免职和 glial fibrillary 的损失开发典型 NMO 损害酸的蛋白质和 AQP4 immunoreactivity。我们的调查结果建议基于 AQP4 的治疗学的潜在的实用程序包括为大脑胀大,损害和癫痫的治疗的 AQP4 水运输功能的小分子的调节的人,以及小分子或对为 NMO 的治疗的 AQP4 有约束力的 NMO-IgG 的 monoclonal 抗体 blockers。 | Alan S VERKMAN Julien RATELADE Andrea ROSSI Hua ZHANG Lukmanee TRADTRANTIP | 2011 | Acta Pharmacologica Sinica2011，32，6： | 17 |
| 5 | Enteric glial cells and their role in gastrointestinal motor abnormalities: Introducing the neuro-gliopathies显示文摘The role of enteric glial cells has somewhat changed from that of mere mechanical support elements, gluing together the various components of the enteric nervous system, to that of active participants in the complex interrelationships of the gut motor and inflammatory events. Due to their multiple functions, spanning from supporting elements in the myenteric plexuses to neurotransmitters, to neuronal homeostasis, to antigen presenting cells, this cell population has probably more intriguing abilities than previously thought. Recently, some evidence has been accumulating that shows how these cells may be involved in the pathophysiological aspects of some diseases. This review will deal with the properties of the enteric glial cells more strictly related to gastrointestinal motor function and the human pathological conditions in which these cells may play a role, suggesting the possibility of enteric neuro- gliopathies. | Gabrio Bassotti Vincenzo Villanacci Simona Fisogni Elisa Rossi Paola Baronio Carlo Clerici Christoph A Maurer Gieri Cathomas Elisabetta Antonelli | 2007 | World Journal of Gastroenterology2007，13，30： | 16 |
| 6 | Inflammation in irritable bowel syndrome:Myth or newtreatment target?显示文摘Low-grade intestinal inflammation plays a key role in the pathophysiology of irritable bowel syndrome(IBS), and this role is likely to be multifactorial. The aim of this review was to summarize the evidence on the spectrum of mucosal inflammation in IBS, highlighting the relationship of this inflammation to the pathophysiology of IBS and its connection to clinical practice. We carried out a bibliographic search in Medline and the Cochrane Library for the period of January 1966 to December 2014, focusing on publications describing an interaction between inflammation and IBS. Several evidences demonstrate microscopic and molecular abnormalities in IBS patients. Understanding the mechanisms underlying low-grade inflammation in IBS may help to design clinical trials to test the efficacy and safety of drugs that target this pathophysiologic mechanism. | Emanuele Sinagra Giancarlo Pompei Giovanni Tomasello Francesco Cappello Gaetano Cristian Morreale Georgios Amvrosiadis Francesca Rossi Attilio Ignazio Lo Monte Aroldo Gabriele Rizzo Dario Raimondo | 2016 | World Journal of Gastroenterology2016，22，7： | 16 |
| 7 | Helicobacter pylori infection: Host immune response, implications on gene expression and microRNAs显示文摘Helicobacter pylori(H. pylori) infection is the most common bacterial infection worldwide. Persistent infection of the gastric mucosa leads to inflammatory processes and may remain silent for decades or progress causing more severe diseases, such as gastric adenocarcinoma. The clinical consequences of H. pylori infection are determined by multiple factors, including host genetic predisposition, gene regulation, environmental factors and heterogeneity of H. pylori virulence factors. After decades of studies of this successful relationship between pathogen and human host, various mechanisms have been elucidated. In this review, we have made an introduction on H. pylori infection and its virulence factors, and focused mainly on modulation of host immune response triggered by bacteria, changes in the pattern of gene expression in H. pylori-infected gastric mucosa, with activation of gene transcription involved in defense mechanisms, inflammatory and immunological response, cell proliferation and apoptosis. We also highlighted the role of bacteria eradication on gene expression levels. In addition, we addressed the recent involvement of different microRNAs in precancerous lesions, gastric cancer, and inflammatory processes induced by bacteria. New discoveries in this field may allow a better understanding of the role of major factors involved in the pathogenic mechanisms of H. pylori. | Aline Cristina Targa Cadamuro Ana Flávia Teixeira Rossi Nathália Maciel Maniezzo Ana Elizabete Silva | 2014 | World Journal of Gastroenterology2014，20，6： | 16 |
| 8 | Estrogens in males: what have we learned in the last 10 years?显示文摘This review focuses on the role of estrogen in men, mainly in male reproduction. The continuing increase in data obtained, and recent discoveries in this area will enable a better understanding of male physiology; these, in turn, will have important clinical implications. | Vincenzo Rochira Antonio R. M. Granata Bruno Madeo Lucia Zirilli Giuseppina Rossi Cesare Carani | 2005 | Asian Journal of Andrology2005，7，1： | 15 |
| 9 | New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond显示文摘Irritable bowel syndrome(IBS)is a chronic,recurring,and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain,distention,and changes in bowel habits.Although there are several drugs for IBS,effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed.Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism,neurohormonal regulation,immune dysfunction,the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS.With regards to therapies for restoring intestinal permeability,multiple studies with prebiotics and probiotics are ongoing,even if to date their efficacy has been limited.In parallel,much progress has been made in targeting low-grade inflammation,especially through the introduction of drugs such as mesalazine and rifaximin,even if a better knowledge of the mechanisms underlying the low-grade inflammation in IBS may allow the design of clinical trials that test the efficacy and safety of such drugs.This literature review aims to summarize the findings related to new and investigational therapeutic agents for IBS,most recently developed in preclinical as well as Phase 1 and Phase 2clinical studies. | Emanuele Sinagra Gaetano Cristian Morreale Ghazaleh Mohammadian Giorgio Fusco Valentina Guarnotta Giovanni Tomasello Francesco Cappello Francesca Rossi Georgios Amvrosiadis Dario Raimondo | 2017 | World Journal of Gastroenterology2017，23，36： | 14 |
| 10 | Therapeutic options for the management of pancreatic cancer显示文摘Since its initial characterization, pancreatic ductal adenocarcinoma has remained one of the most devastating and difficult cancers to treat. Pancreatic cancer is the fourth leading cause of death in the United States, resulting in an estimated 38460 deaths annually. With few screening tools available to detect this disease at an early stage, 94% of patients will die within five years of diagnosis. Despite decades of research that have led to a better understanding of the molecular and cellular signaling pathways in pancreatic cancer cells, few effective therapies have been developed to target these pathways. Other treatment options have included more sophisticated pancreatic cancer surgeries and combination therapies. While outcomes have improved modestly for these patients, more effective treatmentsare desperately needed. One of the greatest challenges in the future of treating this malignancy will be to develop therapies that target the tumor microenvironment and surrounding pancreatic cancer stem cells in addition to pancreatic cancer cells. Recent advances in targeting pancreatic stellate cells and the stroma have encouraged researchers to shift their focus to the role of desmoplasia in pancreatic cancer pathobiology in the hopes of developing newer-generation therapies. By combining novel agents with current cytotoxic chemotherapies and radiation therapy and personalizing them to each patient based on specific biomarkers, the goal of prolonging a patient's life could be achieved. Here we review the most effective therapies that have been used for the treatment of pancreatic cancer and discuss the future potential of therapeutic options. | Maria L Rossi Azeem A Rehman Christopher S Gondi | 2014 | World Journal of Gastroenterology2014，20，32： | 13 |
| 11 | 合并于肝细胞癌的门静脉血栓形成增强超声与螺旋CT的检出及定性显示文摘本研究的目的是对比增强超声(CEUS)与螺旋CT对肝细胞癌(HCC)并发门静脉血栓形成的检出与定性。50例US和多普勒US发现门静脉内血栓形成并经穿刺活检证实的HCC病人被纳入研究。其中13个血栓累及门静脉主干,37个血栓累及门静脉肝段分支。血栓活检后1周内行CEUS和CT检查。由有经验的放射医生以盲法根据每种影像技术分别做出血栓(有/无)与血栓性质(恶性/良性)的诊断,并同病理结果对照,确定血栓检出与定性的准确性。 | S. Rossi G. Ghittoni V .Ravetta F.Torello Viera L.Rosa M.Serassi 高莉(译) 唐光健(校) | 2008 | 国际医学放射学杂志2008，31，5： | 12 |
| 12 | Current approach in the treatment of hepatocellular ca显示文摘Hepatocellular carcinoma (HCC) is the most common malignant hepatobiliary disease; it is responsible for about 1 million deaths per year. Risk factors include hepatitis B and C, hepatic cirrhosis, including alcohol related hepatitis, metabolic and nutritional hepatic damage. The main modality of diffusion is intrahepatic in the natural course of the disease. There are two leading types of treatment: local and systemic. Surgical resection and liver transplantation constitute the most appropriate local treatments and are considered the only real possibility for recovery. Other local approaches include: radiofrequency ablation, percutaneous ethanol ablation, hepatic endoarterial chemoembolization and intrahepatic radiotherapy (SIRT: selective internal radiation therapy). These last treatments are used to control the disease when surgery or transplantation is not achievable; in some cases they are able to prolong survival while theyconstitute mainly a palliative treatment. Systemic treatments include: chemotherapy, immunological and hormonal therapies and, more recently, the introduction of new specific molecular target drugs. At the moment, in this group, the only drug that has given positive results during phase trials (SHARP study) is Sorafenib.Sorafenib represents the only primary systemic therapy that has demonstrated, unlike the other treatments previously described, an increase in survival rate in patients affected with advanced HCC. Currently, other studies are taking place that are further developing the potential of this drug. These studies, including phase trials, aredirected in order to test the activity and safety of new emerging drugs with targeted activity. Examples of these new agents are: Sunitinib, Gef itinib, Cetuximab, Bevacizumab and Erlotinib. | Luigi Rossi Federica Zoratto Anselmo Papa Francesca Iodice Marina Minozzi Luigi Frati Silverio Tomao | 2010 | World Journal of Gastrointestinal Oncology2010，2，9： | 11 |
| 13 | Diagnostic techniques for photonic materials based on Raman and Brillouin spectroscopies显示文摘The elastic and vibrational properties of a material,bulk or planar waveguide,are studied by Brillouin and Raman spectroscopy to follow the process of nanocrystals growth in glass-ceramics. The nanoparticles cause the appearance,in the low fre-quency Raman spectrum,of characteristic peaks,whose position depends on the size of the crystals. At the same time,sharp crystal peaks,due to optical phonons,appear in the Raman spectra,allowing the determination of the nucleated phase,and a frequency shift of the Brillouin peaks is observed. | M. Mattarelli S.Caponi A. Chiappini M. Montagna E. Moser F. Rossi C.Tosello C. Armellini A. Chiasera M. Ferrari Y. Jestin G. Nunzi Conti S. Pelli G.C. Righini | 2007 | Optoelectronics Letters2007，3，3： | 11 |
| 14 | Role of endoscopic ultrasonography in the loco-regional staging of patients with rectal cancer显示文摘The prognosis of rectal cancer(RC) is strictly related to both T and N stage of the disease at the time of diagnosis. RC staging is crucial for choosing the best multimodal therapy: patients with high risk locally advanced RC(LARC) undergo surgery after neoadjuvant chemotherapy and radiotherapy(NAT); those with low risk LARC are operated on after a preoperative short-course radiation therapy; finally, surgery alone is recommended only for early RC. Several imaging methods are used for staging patients with RC: computerized tomography, magnetic resonance imaging, positron emission tomography, and endoscopic ultrasound(EUS). EUS is highly accurate for the loco-regional staging of RC, since it is capable to evaluate precisely the mural infiltration of the tumor(T), especially in early RC. On the other hand, EUS is less accurate in restaging RC after NAT and before surgery. Finally, EUS is indicated for follow-up of patients operated on for RC, where there is a need for the surveillance of the anastomosis. The aim of this review is to highlight the impact of EUS on the management of patients with RC, evaluating its role in both preoperative staging and follow-up of patients after surgery. | Pietro Marone Mario de Bellis Valentina D'Angelo Paolo Delrio Valentina Passananti Elena Di Girolamo Giovanni Battista Rossi Daniela Rega Maura Claire Tracey Alfonso Mario Tempesta | 2015 | World Journal of Gastrointestinal Endoscopy2015，7，7： | 11 |
| 15 | Practical review for diagnosis and clinical management of perihilar cholangiocarcinoma显示文摘Cholangiocarcinoma(CCC)is the most aggressive malignant tumor of the biliary tract.Perihilar CCC(pCCC)is the most common CCC and is burdened by a complicated diagnostic iter and its anatomical location makes surgical approach burden by poor results.Besides its clinical presentation,a multimodal diagnostic approach should be carried on by a tertiary specialized center to avoid missdiagnosis.Preoperative staging must consider the extent of liver resection to avoid post-surgical hepatic failure.During staging iter,magnetic resonance can obtain satisfactory cholangiographic images,while invasive techniques should be used if bile duct samples are needed.Consistently,to improve diagnostic potential,bile duct drainage is not necessary in jaundice,while it is indicated in refractory cholangitis or when liver hypertrophy is needed.Once resecability criteria are identified,the extent of liver resection is secondary to the longitudinal spread of CCC.While in the past type IV pCCC was not considered resectable,some authors reported good results after their treatment.Conversely,in selected unresectable cases,liver transplantation could be a valuable option.Adjuvant chemotherapy is the standard of care for resected patients,while neoadjuvant approach has growing evidences.If curative resection is not achieved,radiotherapy can be added to chemotherapy.This multistep curative iter must be carried on in specialized centers.Hence,the aim of this review is to highlight the main steps and pitfalls of the diagnostic and therapeutic approach to pCCC with a peculiar attention to type IV pCCC. | Daniele Dondossola Michele Ghidini Francesco Grossi Giorgio Rossi Diego Foschi | 2020 | World Journal of Gastroenterology2020，26，25： | 9 |
| 16 | Toll-like receptor 9 polymorphisms and Helicobacter pylori influence gene expression and risk of gastric carcinogenesis in the Brazilian population显示文摘BACKGROUND Toll-like receptors(TLRs)are the first line of host defense,and are involved in Helicobacter pylori(H.pylori)recognition and activation of both inflammatory and carcinogenic processes.The presence of single nucleotide polymorphisms(SNPs)in genes that activate the immune response may modulate the risk of precancerous lesions and gastric cancer(GC).Among them,Toll-like receptor 9(TLR9)polymorphisms have emerged with a risk factor of infectious diseases and cancer,however the studies are still inconclusive.AIM To evaluate whether TLR9 rs5743836 and rs187084 SNPs contribute to the risk of gastric carcinogenesis,and its influence on mRNA expression.METHODS A case-control study was conducted to evaluate two TLR9 SNPs(TLR9-1237 TCrs5743836 and TLR9-1486 CT-rs187084)in chronic gastritis(CG)and GC patients.A total of 609 DNA samples of peripheral blood[248 CG,161 GC,and 200 samples from healthy individuals(C)]were genotyped by polymerase chain reaction-restriction fragment length polymorphism.All samples were tested for the H.pylori infection using Hpx1 and Hpx2 primers.Quantitative polymerase chain reaction by TaqMan?assay was used to quantify TLR9 mRNA from fresh gastric tissues(48 GC,26 CG,and 14 C).RESULTS For TLR9-1237,the TC+CC or CC genotypes were associated with a higher risk of GC than C[recessive model odds ratio(OR)=5.01,95%confidence interval(CI):2.52-9.94,P<0.0001],and the CG(recessive model OR=4.63;95%CI:2.44-8.79,P<0.0001)groups.For TLR9-1486,an association between the CT+TT genotypes and increased risk of both GC(dominant model OR=2.72,95%CI:1.57-4.72,P<0.0001)and CG(dominant model OR=1.79,95%CI:1.15-2.79,P=0.0094)was observed when compared to the C group.Moreover,the presence of TLR9-1237 TC/CC+TLR9-1486 CC genotypes potentiate the risk for this neoplasm(OR=18.57;95%CI:5.06-68.15,P<0.0001).The TLR9 mRNA level was significantly higher in the GC group(RQ=9.24,P<0.0001)in relation to the CG group(RQ=1.55,P=0.0010)and normal mucosa(RQ=1.0).When the samples were grouped according to the polymorphic genotypes and the presence of H.pylori infection,an influence of TLR9-1237 TC+CC polymorphic genotypes(P=0.0083)and H.pylori infection(P<0.0001)was observed on the upregulation of mRNA expression.CONCLUSION Our findings show that TLR9 rs5743836 and rs187084 polymorphisms are associated with a higher risk of carcinogenesis gastric,and that TLR9 mRNA levels can be modulated by TLR9-1237 TC+CC variant genotypes and H.pylori infection. | Manoela Dias Susi de Matos Lourenco Caroline Lucas Trevizani Rasmussen Spencer Luis Marques Payao Ana Flavia Teixeira Rossi Ana Elizabete Silva Juliana Garcia de Oliveira-Cucolo | 2019 | World Journal of Gastrointestinal Oncology2019，11，11： | 9 |
| 17 | Towards a Formal Semantics for UML/MARTE State Machines Based on Hierarchical Timed Automata显示文摘UML is a widely-used,general purpose modeling language.But its lack of a rigorous semantics forbids the thorough analysis of designed solution,and thus precludes the discovery of significant problems at design time.To bridge the gap,the paper investigates the underlying semantics of UML state machine diagrams,along with the time-related modeling elements of MARTE,the profile for modeling and analysis of real-time embedded systems,and proposes a formal operational semantics based on extended hierarchical timed automata.The approach is exemplified on a simple example taken from the automotive domain.Verification is accomplished by translating designed models into the input language of the UPPAAL model checker. | Yu Zhou Luciano Baresi Matteo Rossi | 2013 | Journal of Computer Science & Technology2013，28，1： | 7 |
| 18 | Hypothermic oxygenated perfusion for a steatotic liver graft显示文摘To the Editor:Donor steatosis represents a well-known risk factor for primary non-function,early allograft dysfunction,and biliary complications after liver transplantation(LT)[1,2].Recently,machine perfusion(MP)technology has been implemented in the clinical practice,with the primary intent to assess the graft quality and to optimize the organ selection process[3].A limited number of articles has been published specifically investigated the role of MP in steatotic livers[4–10],with few of them looking at the role of hypothermic MP. | Quirino Lai Franco Ruberto Fabio Melandro Zoe Larghi Laureiro Massimo Rossi Gianluca Mennini | 2020 | Hepatobiliary & Pancreatic Diseases International2020，19，1： | 7 |
| 19 | Synergistic effect of interleukin-10-receptor variants in a case of early-onset ulcerative colitis显示文摘AIM:To investigated the molecular cause of very early-onset ulcerative colitis(UC)in an 18-mo-old affected child.METHODS:We analysed the interleukin-10(IL10)receptor genes at the DNA and RNA level in the proband and his relatives.Beta catenin and tumor necrosis factor-α(TNFα)receptors were analysed in the proteins extracted from peripheral blood cells of the proband,his relatives and familial adenomatous polyposis(FAP)and PTEN hamartoma tumor syndrome(PHTS)patients.Samples were also collected from the proband’s inflamed colorectal mucosa and compared to healthy and tumour mucosa collected from a FAP patient and patients affected by sporadic colorectal cancer(CRC).Finally,we examined mesalazine and azathioprine effects on primary fibroblasts stabilised from UC and FAP patients.RESULTS:Our patient was a compound heterozygote for the IL10RB E47K polymorphism,inherited from his father,and for a novel point mutation within the IL10RA promoter(the-413G->T),inherited from his mother.Beta catenin and tumour necrosis factorαreceptors-Ⅰ(TNFRI)protein were both over-expressed in peripheral blood cells of the proband’s relatives more than the proband.However,TNFRII was over-expressed only in the proband.Finally,both TNFα-receptors were shown to be under-expressed in the inflamed colon mucosa and colorectal cancer tissue compared to healthy colon mucosa.Consistent with this observation,mesalazine and azathioprine induced,in primary fibroblasts,IL10RB and TNFRII over-expression and TNFRI and TNFαunder-expression.We suggest thatβ-catenin and TNFRI protein expression in peripheral blood cells could represent molecular markers of sub-clinical disease in apparently healthy relatives of patients with early-onset UC.CONCLUSION:A synergistic effect of several variant alleles of the IL10 receptor genes,inherited in a Mende-lian manner,is involved in UC onset in this young child. | Martina Galatola Erasmo Miele Caterina Strisciuglio Lorella Paparo Daniela Rega Paolo Delrio Francesca Duraturo Massimo Martinelli Giovanni Battista Rossi Annamaria Staiano Paola Izzo Marina De Rosa | 2013 | World Journal of Gastroenterology2013，19，46： | 7 |
| 20 | Anti-tumour necrosis factor agent and liver injury:literature review,recommendations for management显示文摘Abnormalities in liver function tests,including transient and self-limiting hypertransaminasemia,cholestatic disease and hepatitis,can develop during treatment with anti-tumour-necrosis-factor(TNF)therapy.The optimal management of liver injury related to antiTNF therapy is still a matter of debate.Although some authors recommend discontinuing treatment in case of both a rise of alanine aminotransferase more than5 times the upper limit of normal,or the occurrence of jaundice,there are no standard guidelines for the management of anti-TNF-related liver injury.Bibliographical searches were performed in Pub Med,using the following key words:inflammatory bowel disease(IBD);TNF inhibitors;hypertransaminasemia;drugrelated liver injury;infliximab.According to published data,elevation of transaminases in patients with IBD treated with anti-TNF is a common finding,but resolution appears to be the usual outcome.Anti-TNF agents seem to be safe with a low risk of causing severe drugrelated liver injury.According to our centre experience,we found that hypertransaminasemia was a common,mainly self-limiting finding in our IBD cohort and was not correlated to infliximab treatment on both univariate and multivariate analyses.An algorithm for the management of liver impairment occurring during antiTNF treatment is also proposed and this highlights the need of a multidisciplinary approach and suggests liver biopsy as a key-point in the management decision in case of severe rise of transaminases.However,hepatic injury is generally self-limiting and drug withdrawal seems to be an exception. | Roberta Elisa Rossi Ioanna Parisi Edward John Despott Andrew Kenneth Burroughs James O'Beirne Dario Conte Mark Ian Hamilton Charles Daniel Murray | 2014 | World Journal of Gastroenterology2014，20，46： | 7 |
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