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Polymorphisms of folate metabolism genes in patients with cirrhosis and hepatocellular carcinoma

World Journal of Hepatology 2016年第29期8卷 1234-1243页

作者： Nathália Perpetua Peres Ana Lívia Silva Galbiatti-Dias Marcia Maria Urbanin Castanhole-Nunes Renato Ferreira da Silva Erika Cristina Pavarino Eny Maria Goloni-Bertollo mariangela torreglosa ruiz-cintra Genetics and Molecular Biology Research Unit UPGEM Sao Jose do Rio Preto Medical School FAMERP and Medical School Fundation FUNFARME Study Group of Liver Tumors GETF Hospital de Base Federal University of the Triangulo Mineiro UFTM

AIM To evaluated the association of the risk factors and polymorphisms in MTHFR C677 T, MTHFR A1298 C, MTR A2756 G and MTRR A66 G *** Patients with cirrhosis(n = 116), hepatocellular carcinoma(HCC)(n = 71) and controls(n = 356) were included. Polymerase chain reaction followed by enzymatic digestion and allelic discrimination technique real-time PCR techniques were used for analysis. MINITAB-14.0and SNPstats were utilized for statistical analysis. RESULTS Showed that age ≥ 46 years(OR = 10.31; 95%CI: 5.66-18.76; P < 0.001) and smoking(OR = 0.47; 95%CI: 0.28-0.78; P = 0.003) were associated with cirrhosis. Age ≥ 46 years(OR = 16.36; 95%CI: 6.68-40.05; P < 0.001) and alcohol habit(OR = 2.01; 95%CI: 1.03-3.89; P = 0.039) were associated with HCC. MTHFR A1298 C in codominant model(OR = 3.37; 95%CI: 1.52-7.50; P = 0.014), recessive model(OR = 3.04; 95%CI: 1.43-6.47; P = 0.0051) and additive model(OR = 1.71; 95%CI: 1.16-2.52; P = 0.0072) was associated with HCC, as well as MTR A2756 G in the additive model(OR = 1.68; 95%CI: 1.01-2.77; P = 0.047), and MTRR A66 G in the codominant model(OR = 3.26; 95%CI: 1.54-6.87; P < 0.001), dominant model(OR = 2.55; 95%CI: 1.24-5.25; P = 0.007) and overdominant model(OR = 3.05; 95%CI: 1.66-5.62; P < 0.001). MTR A2756 G in the additive model(OR = 1.54; 95%CI: 1.02-2.33; P = 0.042) and smokers who presented at least one polymorphic allele for MTRR A66G(OR = 1.71; 95%CI: 0.77-3.82; P = 0.0051) showed increased risk for cirrhosis. There was no association between clinical parameters and polymorphisms. CONCLUSION Age ≥ 46 years, alcohol habit and MTR A2756 G, MTHFR A1298 C and MTRR A66 G polymorphisms are associated with an increased risk of HCC development; age ≥ 46 years, tobacco habit and the MTR A2756 G polymorphism are associated with cirrhosis.

关键词： Polymorphism Folate metabolism Liver cirrhosis Hepatocellular carcinoma

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Extrahepatic cholestasis associated with paracoccidioidomycosis:Challenges in the differential diagnosis of biliopancreatic neoplasia

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2531-2540页

作者： Jose Sebastiao dos Santos Vitor de Moura Arrais William Jose Rosseto Ferreira Ricardo Ribeiro Correa Filho mariangela Ottoboni Brunaldi Rafael Kemp Ajith Kumar Sankanrakutty Jorge Elias Junior Fernando Bellissimo-Rodrigues Roberto Martinez Edson Zangiacomi Martinez Jose Celso Ardengh Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo(FMRP-USP) Departamento de Cirurgia e AnatomiaRibeirao Preto 14049-900Sao PauloBrazil Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo(FMRP-USP)Departamento de PatologiaRibeirao Preto 14048900Sao PauloBrazil Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo(FMRP-USP)Departamento de Imagens MédicasHematologia e Oncologia ClínicaRibeirao Preto 14048900Sao PauloBrazil Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo(FMRP-USP)Departamento de Medicina SocialRibeirao Preto 14015-010Sao PauloBrazil Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo(FMRP-USP)Departamento de Clínica MédicaRibeirao Preto 14015-010Sao PauloBrazil Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo(FMRP-USP)Departamento de Cirurgia e AnatomiaRibeirao Preto 14049-900Sao PauloBrazil and Hospital MoriahServico de Endoscopia DigestivaSao Paulo 04084-002Sao PauloBrazil

BACKGROUND Paracoccidioidomycosis(PCM)may involve the hepatic pedicle and peripan creatic lymph nodes,cause damage to the bile duct and manifest,exceptionally,in combination with extrahepatic cholestasis(EHC),making investigation and treatment *** To investigate the management of patients with visceral PCM admitted with *** All patients diagnosed with PCM treated in a public,tertiary teaching hospital between 1982 and 2020 were retrospectively *** also identified with EHC were allocated to two groups according to the treatment approach for the purpose of comparing clinical,laboratory,and imaging findings,resources used for etiological diagnosis,treatment results,and *** analyses were performed using the linear mixed-effects model(random and fixed effects),which was adjusted using the PROC MIXED procedure of the SAS®9.0 software,and Fisher’s exact *** Of 1645 patients diagnosed with PCM,40(2.4%)had *** these,20(50.0%)lived in the rural area and 29(72.5%)were men,with a mean age of 27.1 years(3-65 years).Jaundice as first symptom and weight loss of at least 10 kg were observed in 16 patients(40.0%),and a mass in the head of the pancreas was observed in 8(20.0%).The etiological diagnosis was made by tissue collection during surgery in 4 cases(10.0%)and by endoscopic methods in 3 cases(7.5%).Twenty-seven patients(67.5%)received drug treatment alone(Group 1),whereas 13(32.5%)underwent endoscopic and/or surgical procedures in combination with drug treatment(Group 2).EHC was significantly reduced in both groups(40.7% in Group 1,with a mean time of 3 months;and 38.4% in Group 2,with a mean time of 7.5 months),with no statistically significant difference between *** recurrence rates,associated mainly with treatment nonadherence,were similar in both groups:37% in Group 1 and 15.4% in Group *** mortality rate was 18.5% in Group 1 and 23% in Group 2,with survival estimates of 71.3% and 72.5%,respectively,with

关键词： Cholestasis Jaundice Obstructive Blastomycosis Paracoccidioides Diagnosis Treatment

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Role of spleen elastography in patients with chronic liver diseases

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World Journal of Gastroenterology 2016年第35期22卷 7857-7867页

作者： mariangela Giunta Dario Conte Mirella Fraquelli Gastro-enterology and Endoscopy Unit Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico 20122 Milan Italy Department of Pathophysiology and Organ Transplantation Università degli Studi di Milano

The development of liver cirrhosis and portal hypertension(PH), one of its major complications, are structural and functional alterations of the liver, occurring in many patients with chronic liver diseases(CLD). Actually the progressive deposition of hepatic fibrosis has a key role in the prognosis of CLD patients. The subsequent development of PH leads to its major complications, such as ascites, hepatic encephalopathy, variceal bleeding and decompensation. Liver biopsy is still considered the reference standard for the assessment of hepatic fibrosis, whereas the measurement of hepatic vein pressure gradient is the standard to ascertain the presence of PH and upper endoscopy is the method of choice to detect the presence of oesophageal varices. However, several non-invasive tests, including elastographic techniques, are currently used to evaluate the severity of liver disease and predict its prognosis. More recently, the measurement of the spleen stiffness has become particularly attractive to assess, considering the relevant role accomplished by the spleen in splanchnic circulation in the course of liver cirrhosis and in the PH. Moreover, spleen stiffness as compared with liver stiffness better represents the dynamic changes occurring in the advanced stages of cirrhosis and shows higher diagnostic performance in detecting esophageal varices. The aim of this review is to provide an exhaustive overview of the actual role of spleen stiffness measurement as assessed by several elastographic techniques in evaluating both liver disease severity and the development of cirrhosis complications, such as PH and to highlight its potential and possible limitations.

关键词： Cirrhosis spleen stiffness elastography Portal hypertension Transient elastography

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Nucleoredoxin-like 2 metabolic signaling impairs its potential contribution to neurodegenerative diseases

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Neural Regeneration Research 2023年第3期18卷 529-530页

作者： mariangela Corsi Céline Jaillard Thierry Léveillard Sorbonne Université INSERMCNRSInstitut de la VisionParisFrance

Alzheimer’s disease(AD)threatens the foundations of humanity and our *** is a neurological disorder primarily affecting the elderly through memory disorders,cognitive decline,and loss of *** dramatic consequences of this late-onset disease were illustrated sensitively in Michael Haneke’s masterpiece,*** and governments have invested colossal efforts to develop a treatment for this terrible *** and in the past decade the amyloid cascade has dominated the therapeutic research on AD,but the absence of benefit for patients treated with drugs that reduce brain amyloid deposit questions the role ofβ-amyloid as a causative agent(Herrup,2021).The recent approval of aducanumab by the United States Food and Drug Administration,a drug that targetsβ-amyloid,is at the center of a scandal among clinicians and researchers,as it does not provide therapeutic benefits to patients and is listed among the breakdowns of the year 2021 by Science magazine(Voosen et al.,2021).The lack of progress in curing AD and recent therapeutic failures calls for further exploratory research.

关键词： approval consequences listed

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Antioxidant dietary approach in treatment of fatty liver: New insights and updates

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World Journal of Gastroenterology 2017年第23期23卷 4146-4157页

作者： Alessandra Ferramosca mariangela Di Giacomo Vincenzo Zara Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali Università del Salento Via Provinciale Lecce-Monteroni

Non-alcoholic fatty liver disease(NAFLD) is a common clinicopathological condition, encompassing a range of conditions caused by lipid deposition within liver cells. To date, no approved drugs are available for the treatment of NAFLD, despite the fact that it represents a serious and growing clinical problem in the Western world. Identification of the molecular mechanisms leading to NAFLD-related fat accumulation, mitochondrial dysfunction and oxidative balance impairment facilitates the development of specific interventions aimed at preventing the progression of hepatic steatosis. In this review, we focus our attention on the role of dysfunctions in mitochondrial bioenergetics in the pathogenesis of fatty liver. Major data from the literature about the mitochondrial targeting of some antioxidant molecules as a potential treatment for hepatic steatosis are described and critically analysed. There is ample evidence of the positive effects of several classes of antioxidants, such as polyphenols(i.e., resveratrol, quercetin, coumestrol, anthocyanins, epigallocatechin gallate and curcumin), carotenoids(i.e., lycopene, astaxanthin and fucoxanthin) and glucosinolates(i.e., glucoraphanin, sulforaphane, sinigrin and allyl-isothiocyanate), on the reversion of fatty liver. Although the mechanism of action is not yet fully elucidated, in some cases an indirect interaction with mitochondrial metabolism is expected. We believe that such knowledge will eventually translate into the development of novel therapeutic approaches for fatty liver.

关键词： Hepatic steatosis Fatty liver Lipogenesis Mitochondria Oxidative stress

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Treatment of hepatitis B virus infection in children and adolescents

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World Journal of Gastroenterology 2021年第36期27卷 6053-6063页

作者： mariangela Stinco Chiara Rubino Sandra Trapani Giuseppe Indolfi Department of Health Sciences Pediatric SectionMeyer Children’s University HospitalFlorence 50139Italy Department Neurofarba University of Florence and Meyer Children’s University HospitalFlorence 50139Italy

Hepatitis B virus(HBV)infection is one of the main causes of morbidity and mortality *** children acquire the infection perinatally or during early childhood and develop a chronic hepatitis characterized by a high viral replication and a low-inflammation phase of infection,with normal or only slightly raised *** a conservative approach in children is usually recommended,different therapies exist and different therapeutic approaches are *** main goals of antiviral treatment for children with chronic HBV infection are to suppress viral replication and to warn the disease progression to cirrhosis and hepatocellular carcinoma,although these complications are rare in *** United States Food and Drug Administration(USFDA)and European Medicines Agency(EMA)have approved interferon alfa-2b for children aged 1 year and older,pegylated interferon alfa-2a and lamivudine for children aged 3 years and older,entecavir for use in children aged 2 years and older,and adefovir for use in those 12 years of age and *** disoproxil fumarate is approved by EMA for children aged 2 years and older and by USFDA for treatment in children aged 12 years and ***,EMA has approved the use of tenofovir alafenamide for treatment of children aged 12 years and older or for children weighing more than 35 kg independent of *** narrative review will provide the framework for summarizing indications to antiviral therapy in the management of chronic HBV infection in children and adolescents.

关键词： Hepatitis B Children Adolescents Antiviral therapy Tenofovir disoproxil fumarate Entecavir Interferon

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Lack of transcriptional coordination between mitochondrial and nuclear oxidative phosphorylation genes in the presence of two divergent mitochondrial genomes

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Zoological Research 2022年第1期43卷 111-128页

作者： Ran Xu mariangela Iannello Justin CHavird Liliana Milani Fabrizio Ghiselli Department of Biological Geological and Environmental SciencesUniversity of BolognaBolognaBO 40126Italy Department of Integrative Biology The University of Texas at AustinAustinTX 78712USA

In most eukaryotes,oxidative phosphorylation(OXPHOS)is the main energy production process and it involves both mitochondrial and nuclear *** close interaction between the two genomes is critical for the coordinated function of the OXPHOS *** bivalves show doubly uniparental inheritance(DUI)of mitochondria,where two highly divergent mitochondrial genomes,one inherited through eggs(F-type)and the other through sperm(M-type),coexist in the same ***,it remains a puzzle how nuclear OXPHOS genes coordinate with two divergent mitochondrial genomes in DUI *** this study,we compared transcription,polymorphism,and synonymous codon usage in the mitochondrial and nuclear OXPHOS genes of the DUI species Ruditapes philippinarum using sex-and tissue-specific *** and nuclear OXPHOS genes showed different transcription *** co-transcription signal was observed within mitochondrial(separate for F-and M-type)and within nuclear OXPHOS genes but the signal was weak or absent between mitochondrial and nuclear OXPHOS genes,suggesting that the coordination between mitochondrial and nuclear OXPHOS subunits is not achieved ***-Kreitman and frequency-spectrum based tests indicated that M-type OXPHOS genes deviated significantly from neutrality,and that F-type and M-type OXPHOS genes undergo different selection *** usage analysis revealed that mutation bias and translational selection were the major factors affecting the codon usage bias in different OXPHOS genes,nevertheless,translational selection in mitochondrial OXPHOS genes appears to be less efficient than nuclear OXPHOS ***,we speculate that the coordination between OXPHOS genes may involve post-transcriptional/translational regulation.

关键词： Oxidative phosphorylation Doubly uniparental inheritance Co-transcription Polymorphism Codon usage bias Translational selection

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Exotic break-up modes in heavy ion reactions up to Fermi energies

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Nuclear Science and Techniques 2015年第2期26卷 124-130页

作者： Maria Colonna Virgil Baran Stefano Burrello mariangela Di Prima Paolo Napolitani Carmelo Rizzo INFN-Laboratori Nazionali del Sud Via S Sofia 62Catania I-95123Italy NIPNE-HH Bucharest UniversityBucharest 077125Romania IPN CNRS/IN2P3Universite' Paris-Sud 11Orsay cedex 91406France

We discussed recent studies, within the framework of transport theories, on heavy ion reactions between charge asymmetric systems, from low up to Fermi energies. We concentrated on the analysis of ternary breakup events of dynamical origin occurring in semi-central reactions, where the formation of excited systems in various conditions of shape, excitation energy and spin is observed. At beam energies around 20 A Me V, we showed how this fragmentation mode emerges from the combined action of surface(neck) instabilities and angular momentum effects, leading to the observation of three aligned massive fragments in the exit channel. At Fermi energies, a transition towards a prompt emission of small fragments from the neck region with larger relative velocity with respect to projectile and target remnants is observed. We also focus on isospin sensitive observables, aiming at extracting information on the density dependence of the isovector part of the nuclear effective interaction and of the nuclear symmetry energy.

关键词：重离子反应费米能量不对称系统情调有效相互作用激发系统不稳定性分散模式

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Antegrade scrotal sclerotherapy of internal spermatic veins for varicocele treatment： technique, complications, and results

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Asian Journal of Andrology 2016年第2期18卷 292-295,J0007,J0008页

作者： Alessandro Crestani Gianluca Giannarini Mattia Calandriello Marta Rossanese mariangela Mancini Giacomo Novara Vincenzo Ficarra Academic Medical Centre Hospital Santa Maria della Misericordia Udine Italy Department of Oncologic Surgical and Gastrointestinal Sciences Urologic Unit PadovaItaly Department of Experimental and Clinic Medical Sciences Urology Unit University of Udine Udine Italy.

Varicocele repair is mainly indicated in young adult patients with clinical palpable varicocele and abnormal semen parameters. Varicocele treatment is associated with a significant improvement in sperm concentration, motility, morphology, and pregnancy rate. Antegrade scrotal sclerotherapy （ASS） represented one of the main alternatives to the traditional inguinal or suprainguinal surgical ligation. This article reviews the use of ASS for varicocele treatment. We provide a brief overview of the history of the procedure and present our methods used in ASS. In addition, we review complication and success of ASS, including our own retrospective data of treating 674 patients over the last 17 years. Herein, we analyzed step by step the ASS technique and described our results with an original modified technique with a long follow-up. Between December 1997 and December 2014, we performed 674 ASS. Mean operative time was 14 min （range 9 to 50 min）. No significant intraoperative complications were reported. Within 90 days from the procedure, postoperative complications were recorded in overall 49 （7.2%） patients. No major complications were recorded. A persistent/recurrent varicocele was detected in 40 （5.9%） cases. In 32/40 （80%） cases, patients showed preoperative grade III varicoceles. In patients with a low sperm number before surgery, sperm count improved from 13 x 106 to 21 x 106 m1-1 （P〈 0.001）. The median value of the percentage of progressive motile forms at 1 h improved from 25% to 45% （P 〈 0.001）. Percentage of normal forms increased from 17% before surgery to 35% 1 year after the procedure （P 〈 0.001）. In the subgroup of the 168 infertile patients, 52 （31%） fathered offspring at a 12-month-minimum follow-up. Therefore, ASS is an effective minimal invasive treatment for varicocele with low recurrence/persistence rate.

关键词： antegrade scrotal sclerotherapy male infertility outcomes varicocele

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Modeling and simulation of InAs/GaAs quantum dot lasers

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Optoelectronics Letters 2011年第2期7卷 122-125页

作者：吕少锋 Ivo Montrosset mariangela Gioannini 宋书中马建伟 School of Electronic Information Engineering Henan University of Science and Technology Electronic Department Politecnico di Torino

Based on the analysis of carrier dynamics in quantum dots （QDs）, the numerical model of InAs/GaAs QD laser is developed by means of complete rate equations. The model includes four energy levels and among them three energy levels join in lasing. A simulation is conducted by MATLAB according to the rate equation model we obtain. The simulation results of PI characteristic, gain characteristic and intensity modulation response are reasonable. Also, the relations between the left facet reflectivity of laser cavity and threshold current as well as modulation bandwidth are studied. It is indicated that the left facet reflectivity increasing can result in reduced threshold current and improved mo6ulation bandwidth, which is in accordance with experimental results. The internal mechanism of QD lasers is fully described with the rate equation model, which is helpful for QD lasers research.

关键词： Computer simulation Mathematical models Modulation Optical waveguides Reflection Semiconductor quantum dots

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