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| 1 | Microbiota and the gut-liver axis:Bacterial translocation,inflammation and infection in cirrhosis显示文摘Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota.In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria(i.e.,gram negative species)and a decrease in autochthonous familiae.Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences.We therefore described the features of the complex interaction between gut microbiota and cirrhotic host,the so called'gut-liver axis',with a particular attention to the acquired risk of bacterial translocation,systemic inflammation and the relationship with systemic infections in the cirrhotic patient.Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis. | Valerio Giannelli Vincenza Di Gregorio Valerio Iebba Michela Giusto Serena Schippa Manuela Merli Ulrich Thalheimer | 2014 | World Journal of Gastroenterology2014，20，45： | 43 |
| 2 | Follow-up of intestinal metaplasia in the stomach: When, how and why显示文摘Gastric cancer remains the second most frequent cause of cancer-related mortality in the world. Screening programs in some Asian countries are impractical in the majority of other countries worldwide. Therefore, follow-up of precancerous lesions is advisable for secondary gastric cancer prevention. Intestinal metaplasia (IM) is recognized as a precancerous lesion for gastric cancer, increasing the risk by 6-fold. IM is highly prevalent in the general population, being detected in nearly 1 of every 4 patients undergoing upper endoscopy. The IM prevalence rate is significantly higher in patients with Helicobacter pylori (H. pylori) infection, in first-degree relatives of gastric cancer patients, in smokers and it increases with patient age. IM is the 'breaking point' in the gastric carcinogenesis cascade and does not appear to regress following H. pylori eradication, although the cure of infection may slow its progression. Gastric cancer risk is higher in patients with incomplete-type IM, in those with both antral and gastric body involvement, and the risk significantly increases with IM extension over 20% of the gastric mucosa. Scheduled endoscopic control could be cost-effective in IM patients, depending on the yearly incidence of gastric cancer in IM patients, the stage of gastric cancer at diagnosis discovered at surveillance, and the cost of endoscopy. As a pragmatic behavior, yearly endoscopic control would appear justified in all IM patients with at least one of these conditions: (1) IM extension > 20%; (2) the presence of incomplete type IM; (3) first-degree relative of gastric cancer patients; and (4) smokers. In the remaining IM patients, a less intensive (2-3 years) could be proposed. | Angelo Zullo Cesare Hassan Adriana Romiti Michela Giusto Carmine Guerriero Roberto Lorenzetti Salvatore MA Campo Silverio Tomao | 2012 | World Journal of Gastrointestinal Oncology2012，4，3： | 25 |
| 3 | MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis b- and c-related-hepatocellularcarcinoma显示文摘Aim of the present review is to summarize the current knowledge about the potential relationship between mi RNAs and hepatitis B virus(HBV)-hepatitis C virus(HCV) related liver diseases. A systematic computerbased search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Statement, was performed to identify relevant studies on usefulness of serum/plasma/urine mi RNAs, as noninvasive biomarkers for early detection of HBV and HCV-induced hepatocellular carcinoma(HCC) development, as well as for its prognostic evaluation. The used Medical Subject Headings terms and keywords were: 'HBV', 'HCV', 'hepatocellular carcinoma', 'micro RNAs', 'mi RNAs', 'diagnosis', 'prognosis', 'therapy', 'treatment'. Some serum/plasma mi RNAs, including mi R-21, mi R-122, mi-125a/b, mi R-199a/b, mi R-221, mi R-222, mi R-223, mi R-224 might serve as biomarkers for early diagnosis/prognosis of HCC, but, to date, not definitive results or well-defined panels of mi RNAs have been obtained. More well-designed studies, focusing on populations of different geographical areas and involving larger series of patients, should be carried out to improve our knowledge on the potential role of mi RNAs for HCC early detection and prognosis. | Sirio Fiorino Maria Letizia Bacchi-Reggiani Michela Visani Giorgia Acquaviva Adele Fornelli Michele Masetti Andrea Tura Fabio Grizzi Matteo Zanello Laura Mastrangelo Raffaele Lombardi Luca Di Tommaso Arrigo Bondi Sergio Sabbatani Andrea Domanico Carlo Fabbri Paolo Leandri Annalisa Pession Elio Jovine Dario de Biase | 2016 | World Journal of Gastroenterology2016，22，15： | 25 |
| 4 | Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease显示文摘AIM:To explore the association between hepatocellular carcinoma(HCC) and type 2 diabetes mellitus, describe the temporal relations between the onset of diabetes and the development of HCC and evaluate the possible effects of antidiabetic therapy on HCC risk.METHODS:We recruited 465 HCC patients, 618 with cirrhosis and 490 control subjects.We evaluated the odds ratio(OR) for HCC by univariate and multivariate analysis.Moreover, OR for HCC in diabetic subjects treated with insulin or sulphanylureas and with metformin were calculated.RESULTS:The prevalence of diabetes mellitus was 31.2% in HCC, 23.3% in cirrhotic patients and 12.7% in the Control group.By univariate and multivariate analysis, the OR for HCC in diabetic patients were respectively 3.12(CI 2.2-4.4, P < 0.001) and 2.2(CI 1.2-4.4, P = 0.01).In 84.9% of cases, type 2 diabetes mellitus was present before the diagnosis of HCC.Moreover, we report an OR for HCC of 2.99(CI 1.34-6.65, P = 0.007) in diabetic patients treated with insulin or sulphanylureas, and an OR of 0.33(CI 0.1-0.7, P = 0.006) in diabetic patients treated with metformin.CONCLUSION:Our study confi rms that type 2 diabetes mellitus is an independent risk factor for HCC and pre-exists in the majority of HCC patients.Moreover, in male patients with type 2 diabetes mellitus, our data shows a direct association of HCC with insulin and sulphanylureas treatment and an inverse relationship with metformin therapy. | Valter Donadon Massimiliano Balbi Michela Ghersetti Silvia Grazioli Antonio Perciaccante Giovanni Della Valentina Rita Gardenal Maria Dal Mas Pietro Casarin Giorgio Zanette Cesare Miranda | 2009 | World Journal of Gastroenterology2009，15，20： | 23 |
| 5 | role of microRNAs in the main molecular pathways of hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC) is the most common primary liver malignant neoplasia. HCC is characterized by a poor prognosis. The need to find new molecular markers for its diagnosis and prognosis has led to a progressive increase in the number of scientific studies on this topic. MicroRNAs(miRNAs) are small noncoding RNA that play a role in almost all main cellular pathways. miRNAs are involved in the regulation of expression of the major tumor-related genes in carcinogenesis, acting as oncogenes or tumor suppressor genes. The aim of this review was to identify papers published in 2017 investigating the role of miRNAs in HCC tumorigenesis. miRNAs were classified according to their role in the main molecular pathways involved in HCC tumorigenesis:(1) m TOR;(2) Wnt;(3) JAK/STAT;(4) apoptosis; and(5) MAPK. The role of miRNAs in prognosis/response prediction was taken into consideration. Bearing in mind that the analysis of miRNAs in serum and other body fluids would be crucial for clinical management, the role of circulating miRNAs in HCC patients was also investigated. The most represented mi RNA-regulated pathway in HCC is m TOR, but apoptosis, Wnt, JAK/STAT or MAPK pathways are also influenced by mi RNA expression levels. These miRNAs could thus be used in clinical practice as diagnostic, prognostic or therapeutic targets for HCC treatment. | Francesco Vasuri Michela Visani Giorgia Acquaviva Thomas Brand Michelangelo Fiorentino Annalisa Pession Giovanni Tallini Antonia D’Errico Dario de Biase | 2018 | World Journal of Gastroenterology2018，24，25： | 16 |
| 6 | Hepatocellular carcinoma:Surgical perspectives beyond the barcelona clinic liver cancer recommendations显示文摘The barcelona clinic liver cancer(BCLC)staging system has been approved as guidance for hepatocellular carcinoma(HCC)treatment guidelines by the main Western clinical liver associations.According to the BCLC classification,only patients with a small single HCC nodule without signs of portal hypertension or hyperbilirubinemia should undergo liver resection.In contrast,patients with intermediate-advanced HCC should be scheduled for palliative therapies,even if the lesion is resectable.Recent studies report good short-term and long-term outcomes in patients with intermediate-advanced HCC treated by liver resection.Therefore,this classification has been criticised because it excludes many patients who could benefit from curative resection.The aim of this review was to evaluate the role of surgery beyond the BCLC recommendations.Safe liver resection can be performed in patients with portal hypertension and well-compensated liver function with a 5-year survival rate of 50%.Surgery also offers good long-term result in selected patients with multiple or large HCCs with a reported 5-year survival rate of over 50%and 40%,respectively.Although macrovascular invasion is associated with a poor prognosis,liver resection provides better long-term results than palliative therapies or best supportive care.Recently,researchers have identified several genes whose altered expression influences the prognosis of patients with HCC.These genes may be useful for classifying the biological behaviour of different tumours.A revision of the BCLC classification should be introduced to provide the best treatment strategy and to ensure the best prognosis in patients with HCC. | Alfredo Guglielmi rea Ruzzenente Simone Conci Alessro Valdegamberi Marco Vitali Francesca Bertuzzo Michela De Angelis Guido Mantovani Calogero Iacono | 2014 | World Journal of Gastroenterology2014，20，24： | 16 |
| 7 | Early endoscopic ultrasonography in acute biliary pancreatitis: A prospective pilot study显示文摘AIM: To investigate the clinical usefulness of early endoscopic ultrasonography(EUS) in the management of acute biliary pancreatitis(ABP).METHODS: All consecutive patients entering the emergency department between January 2010 and December 2012 due to acute abdominal pain and showing biochemical and/or radiological findings consistent with possible ABP were prospectively enrolled. Patients were classified as having a low,moderate,or high probability of common bile duct(CBD) stones,according to the established risk stratification. Exclusion criteria were: gastrectomy or patient in whom the cause of biliary obstruction was already identified by ultrasonography. All enrolled patients underwent EUS within 48 h of their admission. Endoscopic retrograde cholangiopancreatography was performed immediately after EUS only in those cases with proven CBD stones or sludge. The following parameters were investigated:(1) clinical: age,sex,fever;(2) radiological: dilated CBD; and(3) biochemical: bilirubin,AST,ALT,g GT,ALP,amylase,lipasis,PCR. Association between presence of CBD stone at EUS and the individual predictors wereassessed by univariate logistic regression. Predictors significantly associated with CBD stones(P < 0.05) were entered in a multivariate logistic regression model.RESULTS: A total of 181 patients with pancreatitis were admitted to the emergency department between January 2010 and December 2012. After exclusion criteria a total of 71 patients(38 females,53.5%,mean age 58 ± 20.12 years,range 27-89 years; 33 males,46.5%,mean age 65 ± 11.86 years,range 41-91 years) were included in the present study. The probability of CBD stones was considered low in 21 cases(29%),moderate in 26(37%),and high in the remaining 24(34%). The 71 patients included in the study underwent EUS,which allowed for a complete evaluation of the target sites in all the cases. The procedure was completed in a mean time of 14.7 min(range 9-34 min),without any notable complications.The overall CBD stone frequency was 44%(31 of 71),with a significant increase from the group at low pretest probability to that at moderate(OR = 5.79,P = 0.01) and high(OR = 4.25,P = 0.03) pretest probability.CONCLUSION: Early EUS in ABP allows,if appropriate,immediate endoscopic treatment and significant spare of unnecessary operative procedures thus reducing possible related complications. | Andrea Anderloni Marianna Galeazzi Marco Ballarè Michela Pagliarulo Marco Orsello Mario Del Piano Alessandro Repic | 2015 | World Journal of Gastroenterology2015，21，36： | 14 |
| 8 | Accuracy and responses of genomic selection on key traits in apple breeding显示文摘The application of genomic selection in fruit tree crops is expected to enhance breeding eficiency by increasing prediction accuracy,increasing selection intensity and decreasing generation interval.The objectives of this study were to assess the accuracy of prediction and selection response in commercial apple breeding programmes for key traits.The training population comprised 977 individuals derived from 20 pedigreed fllsib families.Historic phenotypic data were available on 10 traits related to productivity and fruit external appearance and genotypic data for 7829 SNPs obtained with an llumina 20K SNP array.From these data,a genome-wide prediction model was built and subsequently used to calculate genomic breeding values of five application fllsib families.The application families had genotypes at 364 SNPs from a dedicated 512 SNP array,and these genotypic data were extended to the high-density level by imputation.These five families were phenotyped for 1 year and their phenotypes were compared to the predicted breeding values.Accuracy of genomic prediction across the 10 traits reached a maximum value of 0.5 and had a median value of 0.19.The accuracies were strongly affected by the phenotypic distribution and heritability of traits.In the largest family,significant selection response was observed for traits with high heritability and symmetric phenotypic distribution.Traits that showed non-significant response often had reduced and skewed phenotypic variation or low heritability.Among the five application families the accuracies were uncorrelated to the degree of relatedness to the training population.The results underline the potential of genomic prediction to accelerate breeding progress in outbred fruit tree crops that still need to overcome long generation intervals and extensive phenotyping costs. | Hélène Muranty Michela Troggio Inès Ben Sadok Mehdi Al Rifaï Annemarie Auwerkerken Elisa Banchi Riccardo Velasco Piergiorgio Stevanato W.Eric van de Weg Mario Di Guardo Satish Kumar François Laurens Marco C.A.M.Bink | 2015 | Horticulture Research2015，2，1： | 14 |
| 9 | MicroRNAs in lung cancer显示文摘Micro RNAs have become recognized as key players in the development of cancer. They are a family of small non-coding RNAs that can negatively regulate the expression of cancer-related genes by sequenceselective targeting of m RNAs, leading to either m RNA degradation or translational repression. Lung cancer is the leading cause of cancer-related death worldwide with a substantially low survival rate. Micro RNAs have been confirmed to play roles in lung cancer development, epithelial-mesenchymal transition and response to therapy. They are also being studied for their future use as diagnostic and prognostic biomarkers and as potential therapeutic targets. In this review we focus on the role of dysregulated micro RNA expression in lung tumorigenesis. We also discuss the role of micro RNAs in therapeutic resistance and as biomarkers. We further look into the progress made and challenges remaining in using micro RNAs for therapy in lung cancer. | Pooja Joshi Justin Middleton Young-Jun Jeon Michela Garofalo | 2014 | World Journal of Methodology2014，4，2： | 13 |
| 10 | Micro RNAs as lung cancer biomarkers显示文摘Lung cancer is the leading cause of cancer mortality worldwide. Its high mortality is due to the poor prognosis of the disease caused by a late disease presentation, tumor heterogeneities within histological subtypes, and the relatively limited understanding of tumor biology. Importantly, lung cancer histological subgroups respond differently to some chemotherapeutic substances and side effects of some therapies appear to vary between subgroups. Biomarkers able to stratify for the subtype of lung cancer, prognosticate the course of disease, or predict the response to treatment are in high demand. In the last decade, microR NAs(miR NAs), measured in resected tumor samples or in fine needle aspirate samples have emerged as biomarkers for tumor diagnosis, prognosis and prediction of response to treatment, due to the ease of their detection and in their extreme specificity. Moreover, miR NAs present in sputum, in plasma, in serum or in whole blood have increasingly been explored in the last five years as less invasive biomarkers for the early detection of cancers. In this review we cover the increasing amounts of datathat have accumulated in the last ten years on the use of miR NAs as lung cancer biomarkers. | Valerio Del Vescovo Margherita Grasso Mattia Barbareschi Michela A Denti | 2014 | World Journal of Clinical Oncology2014，5，4： | 11 |
| 11 | untreatable hepatocellular 癌的自然历史: 回顾的队研究显示文摘 AIM:To investigate the clinical course of untreatable hepatocellular carcinoma(HCC) identified at any stage and to identify factors associated with mortality.METHODS:From January 1999 to December 2010,320 out of 825 consecutive patients with a diagnosis of HCC and not appropriate for curative or palliative treatments were followed and managed with supportive therapy.Cirrhosis was diagnosed by histological or clinical features and liver function was evaluated according to Child-Pugh score.The diagnosis of HCC was performed by Ultra-Sound guided biopsy or by multiphasic contrast-enhanced computed tomography or gadolinium-enhanced magnetic resonance imaging.Data were collected for each patient including all clinical,laboratory and imaging variables necessary for the outcome prediction staging systems considered.HCC staging was performed according Barcelona Clinic Liver Cancer(BCLC) and Cancer of the Liver Italian Program scores.Follow-up time was defined as the number of months from the diagnosis of HCC to death.Prognostic baseline variables were analyzed by multivariate Cox analysis to identify the independent predictors of survival.RESULTS:Seventy-five per cent of patients had hepatitis C.Ascites was present in 169 patients(53%),while hepatic encephalopathy was present in 49 patients(15%).The Child-Pugh score was class A in 105 patients(33%),class B in 142 patients(44%),and class C in 73 patients(23%).One hundred patients(31%) had macroscopic vascular invasion and/or extrahepatic spread of the tumor.A single lesion > 10 cm was observed in 34 patients(11%),while multinodular HCC was present in 189 patients(59%).Thirty nine patients(12%) were BCLC early(A) stage,55(17%) were BCLC intermediate(B) stage,124(39%) were BCLC advanced(C) stage,and 102(32%) were endstage BCLC(D).At the time of this analysis(July 2011),28(9%) patients were still alive.Six(2%) patients who were lost during follow-up were censored at the last visit.The overall median survival was 6.8 mo,and the 1-year survival was 32%.The 1-year survival according to BCLC classes was 100%,79%,12% and 0%,for BCLC A,B,C and D,respectively.There was a significant difference in survival between each BCLC class.The median survival of patients of BCLC stages A,B,C and D was 33,17.4,6.9,and 1.8 mo,respectively(P < 0.05 for comparison between stages).The median survival of Child-Pugh A,B and C classes were 9.8 mo(range 6.4-13),6.1(range 4.9-7.3),and 3.7(range 1.5-6),respectively(P < 0.05 for comparison between stages).By univariate analysis,the variables significantly associated to an increased liklihood of mortality were Eastern Cooperative Oncology Group performance status(PS),presence of ascites,low level of albumin,elevated level of bilirubin,international normalized ratio(INR) and Log-[(α fetoprotein(AFP)].At multivariate analysis,mortality was independently predicted by bad PS(P < 0.0001),high INR values(P = 0.0001) and elevated Log-(AFP) levels(P = 0.009).CONCLUSION:This study confirms the heterogeneous behavior of untreated HCC.BCLC staging remains an important prognostic guide and may be important in decision-making for palliative treatment. | Giuseppe Cabibbo Marcello Maida Chiara Genco Pietro Parisi Marco Peralta Michela Antonucci Giuseppe Brancatelli Calogero Cammà Antonio Craxì Vito Di Marco | 2012 | World Journal of Hepatology2012，4，9： | 11 |
| 12 | An integrated approach for increasing breeding efficiency in apple and peach in Europe显示文摘Despite the availability of whole genome sequences of apple and peach,there has been a considerable gap between genomics and breeding.To bridge the gap,the European Union funded the FruitBreedomics project(March 2011 to August 2015)involving 28 research institutes and private companies.Three complementary approaches were pursued:(i)tool and software development,(ii)deciphering genetic control of main horticultural traits taking into account allelic diversity and(iii)developing plant materials,tools and methodologies for breeders.Decisive breakthroughs were made including the making available of ready-to-go DNA diagnostic tests for Marker Assisted Breeding,development of new,dense SNP arrays in apple and peach,new phenotypic methods for some complex traits,software for gene/QTL discovery on breeding germplasm via Pedigree Based Analysis(PBA).This resulted in the discovery of highly predictive molecular markers for traits of horticultural interest via PBA and via Genome Wide Association Studies(GWAS)on several European genebank collections.FruitBreedomics also developed pre-breeding plant materials in which multiple sources of resistance were pyramided and software that can support breeders in their selection activities.Through FruitBreedomics,significant progresses were made in the field of apple and peach breeding,genetics,genomics and bioinformatics of which advantage will be made by breeders,germplasm curators and scientists.A major part of the data collected during the project has been stored in the FruitBreedomics database and has been made available to the public.This review covers the scientific discoveries made in this major endeavour,and perspective in the apple and peach breeding and genomics in Europe and beyond. | Francois Laurens Maria JoséAranzana Pere Arus Daniele Bassi Marco Bink Joan Bonany Andrea Caprera Luca Corelli-Grappadelli Evelyne Costes Charles-Eric Durel Jehan-Baptiste Mauroux Hélène Muranty Nelson Nazzicari Thierry Pascal Andrea Patocchi Andreas Peil Bénédicte Quilot-Turion Laura Rossini Alessandra Stella Michela Troggio Riccardo Velasco Eric van de Weg | 2018 | Horticulture Research2018，5，1： | 10 |
| 13 | Transcranial direct current stimulation enhances theory of mind in Parkinson’s disease patients with mild cognitive impairment:a randomized,double-blind,sham-controlled study显示文摘Background:Parkinson’s Disease(PD)with mild cognitive impairment(MCI)(PD-MCI)represents one of the most dreaded complications for patients with PD and is associated with a higher risk of developing dementia.Although transcranial direct current stimulation(tDCS)has been demonstrated to improve motor and non-motor symptoms in PD,to date,no study has investigated the effects of tDCS on Theory of Mind(ToM),i.e.,the ability to understand and predict other people’s behaviours,in PD-MCI.Methods:In this randomized,double-blind,sham-controlled study,we applied active tDCS over the medial frontal cortex(MFC)to modulate ToM performance in twenty patients with PD-MCI.Twenty matched healthy controls(HC)were also enrolled and were asked to perform the ToM task without receiving tDCS.Results:In the patients with PD-MCI,i)ToM performance was worse than that in the HC,ii)ToM abilities were poorer in those with fronto-executive difficulties,and iii)tDCS over the MFC led to significant shortening of latency for ToM tasks.Conclusions:We show for the first time that active tDCS over the MFC enhances ToM in patients with PD-MCI,and suggest that non-invasive brain stimulation could be used to ameliorate ToM deficits observed in these patients. | Mauro Adenzato Rosa Manenti Ivan Enrici Elena Gobbi Michela Brambilla Antonella Alberici Maria Sofia Cotelli Alessandro Padovani Barbara Borroni Maria Cotelli | 2019 | Translational Neurodegeneration2019，8，1： | 9 |
| 14 | Electrical storm: A clinical and electrophysiological overview显示文摘Electrical storm(ES) is a clinical condition characterized by three or more ventricular arrhythmia episodes leading to appropriate implantable cardioverterdefibrillator(ICD) therapies in a 24 h period. Mostly, arrhythmias responsible of ES are multiple morphologies of monomorphic ventricular tachycardia(VT), but polymorphic VT and ventricular fibrillation can also result in ES. Clinical presentation is very dramatic in most cases, strictly related to the cardiac disease that may worsen electrical and hemodynamic decompensation. Therefore ES management is challenging in the majority of cases and a high mortality is the rule both in the acute and in the long-term phases. Different underlying cardiomyopathies provide significant clues into the mechanism of ES, which can arise in the setting of structural arrhythmogenic cardiomyopathies or rarely in patients with inherited arrhythmic syndrome, impacting on pharmacological treatment, on ICD programming, and on the opportunity to apply strategies of catheter ablation. This latter has become a pivotal form of treatment due to its high efficacy in modifying the arrhythmogenic substrate and in achieving rhythm stability, aiming at reducing recurrences of ventricular arrhythmia and at improving overall survival. In this review, the most relevant epidemiological and clinical aspects of ES, with regard to the acute and long-term follow-up implications, were evaluated, focusing on these novel therapeutic strategies of treatment. | Sergio Conti Salvatore Pala Viviana Biagioli Giuseppe Del Giorno Martina Zucchetti Eleonora Russo Vittoria Marino Antonio Dello Russo Michela Casella Francesca Pizzamiglio Valentina Catto Claudio Tondo Corrado Carbucicchio | 2015 | World Journal of Cardiology2015，7，9： | 9 |
| 15 | Pharmacogenetics of the systemic treatment in advanced hepatocellular carcinoma显示文摘Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. To date, most patients with HCC are diagnosed at an advanced tumor stage, excluding them from potentially curative therapies (i.e., resection, liver transplantation, percutaneous ablation). Treatments with palliative intent include chemoembolization and systemic therapy. Among systemic treatments, the small-molecule multikinase inhibitor sorafenib has been the only systemic treatment available for advanced HCC over 10 years. More recently, other smallmolecule multikinase inhibitors (e.g., regorafenib, lenvatinib, cabozantinib) have been approved for HCC treatment. The promising immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab) are still under investigation in Europe while in the US nivolumab has already been approved by FDA in sorafenib refractory or resistant patients. Other molecules, such as the selective CDK4/6inhibitors (e.g., palbociclib, ribociclib), are in earlier stages of clinical development, and the c- MET inhibitor tivantinib did not show positive results in a phase III study. However, even if the introduction of targeted agents has led to great advances in patient response and survival with an acceptable toxicity profile, a remarkable inter-individual heterogeneity in therapy outcome persists and constitutes a significant problem in disease management. Thus, the identification of biomarkers that predict which patients will benefit from a specific intervention could significantly affect decision-making and therapy planning. Germ-line variants have been suggested to play an important role in determining outcomes of HCC systemic therapy in terms of both toxicity and treatment efficacy. Particularly, a number of studies have focused on the role of genetic polymorphisms impacting the drug metabolic pathway and membrane translocation as well as the drug mechanism of action as predictive/prognostic markers of HCC treatment. The aim of this review is to summarize and critically discuss the pharmacogenetic literature evidences, with particular attention to sorafenib and regorafenib, which have been used longer than the others in HCC treatment. | Elena De Mattia Erika Cecchin Michela Guardascione Luisa Foltran Tania Di Raimo Francesco Angelini Mario D’Andrea Giuseppe Toffoli | 2019 | World Journal of Gastroenterology2019，25，29： | 8 |
| 16 | Dorsolateral prefrontal cortex, working memory and episodic memory processes: insight through transcranial magnetic stimulation techniques显示文摘The ability to recall and recognize facts we experienced in the past is based on a complex mechanism in which several cerebral regions are implicated. Neuroimaging and lesion studies agree in identifying the frontal lobe as a crucial structure for memory processes, and in particular for working memory and episodic memory and their relationships. Furthermore, with the introduction of transcranial magnetic stimulation (TMS) a new way was proposed to investigate the relationships between brain correlates, memory functions and behavior. The aim of this review is to present the main findings that have emerged from experiments which used the TMS technique for memory analysis. They mainly focused on the role of the dorsolateral prefrontal cortex in memory process. Furthermore, we present state-of-the-art evidence supporting a possible use of TMS in the clinic. Specifically we focus on the treatment of memory deficits in depression and anxiety disorders. | Michela Balconi | 2013 | Neuroscience Bulletin2013，29，3： | 8 |
| 17 | Long lasting response to second-line everolimus in kidney cancer显示文摘In the case presented here, everolimus was administered after first line therapy with sunitinib in a patient with metastatic renal cell carcinoma. The safety profile was excellent. The prolonged progression-free survival(PFS) obtained with everolimus in this case is of peculiar interest, as it is a multiple of the median PFS obtained in with everolimus in the regulatory trial. Such finding suggests that a subset of patients with renal cell carcinma may particularly benefit from everolimus. | Antonella Virtuoso Tania Policastro Michela Izzo Piera Federico Carlo Buonerba Pasquale Rescigno Giuseppe Di Lorenzo | 2013 | World Journal of Clinical Cases2013，1，5： | 6 |
| 18 | Management of portopulmonary hypertension:New perspectives显示文摘Portopulmonary hypertension(PPHTN)is a known complication of cirrhosis.Moderate-to-severe PPHTN implies an extremely poor prognosis.It occurs in 5%-10%of patients referred for liver transplantation(LT),and probably with an higher incidence in patients with large portosystemic shunts.Patients with moderate-tosevere pulmonary hypertension have been previously excluded from LT because of the extremely high surgical risk and since the post-transplant outcome reported was poor.Recently,new perspectives in the management of patients with portopulmonary hypertension are emerging.In fact,some pulmonary vasoactive drugs have become routine in the treatment of patients with idiopathic pulmonary hypertension.These drugs,particularly epoprostenol,have been recently introduced in the treatment of patients with PPHTN,and have been shown to be effective in reducing pulmonary artery pressure as well as pulmonary vascular resistances.Furthermore,recent studies seem to demonstrate that treatment with pulmonary vasoactive drugs could allow liver transplantation with acceptable surgical risks and excellent survival.Although there are not large series nor prospective studies addressing this topic,the clinical scenario of patients with PPHTN seems to be positively changing. | Luigi Mancuso Francesca Scordato Michela Pieri Eliana Valerio Andrea Mancuso | 2013 | World Journal of Gastroenterology2013，19，45： | 5 |
| 19 | The Ins and Outs of the Rice AGAMOUS Subfamily显示文摘无性器官的亚科的基因被显示了在繁殖机关身份决心,水果,和种子开发起关键作用。他们深深地在 eudicot 种类并且特别在 Arabidopsis 被学习了。最近,米饭的无性器官的亚科在花开发为他们的角色被学习了,庞大的数据被产生了。在这评论,我们提供这些数据的概述并且讨论在米饭和 Arabidopsis 之间的基因函数的保存。 | Ludovico Dreni Michela Osnato Martin M. Kater | 2013 | Molecular Plant2013，6，3： | 5 |
| 20 | Rectal hepatoid carcinoma with liver metastases in a patient affected by ulcerative colitis显示文摘BACKGROUND:Hepatoid tumors(HTs)are rare extra-hepatic neoplasms with the histological features, biochemical profile and,sometimes,even clinical course of hepatocellular carcinoma.We present a case of rectal hepatoid adenocarcinoma with metachronous liver metastases. METHODS:Four months after total procto-colectomy for a rectal adenocarcinoma(Astler-Coller C2),a 42-year-old man with ulcerative colitis showed hypoechoic masses in the hepatic parenchyma by abdominal ultrasonography. Carcinoembryonic antigen was normal,but alpha- fetoprotein was 32 000μg/L.Fine-needle biopsy revealed that liver masses were positive for hepatocellular carcinoma. The patient underwent left hepatectomy and alcoholisation of a small deep nodule in segment 8. RESULTS:Immunohistochemistry and albumin mRNA in situ hybridization suggested that the nodules were metastases of a HT.The patient was well during the first 6 months and refused any adjuvant chemotherapy.He died from liver failure 19 months after initial diagnosis. CONCLUSIONS:HT is a rare colon cancer.The preoperative diagnosis of this tumor requires a high degree of suspicion,the availability of a panel of immunohistochemical markers,and a certain amount of luck.The prognosis is poor despite an aggressive andmultimodal therapeutic strategy.So far,none of the hypotheses proposed about the origin and the biology of these tumors is convincing. | Giacomo Borgonovo Francesco Razzetta Michela Assalino Emanuela Varaldo Maria Puglisi Paola Ceppa | 2008 | Hepatobiliary & Pancreatic Diseases International2008，7，5： | 5 |
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