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Tenofovir vs lamivudine plus adefovir in chronic hepatitis B:TEnOSIMP-B study

World Journal of Gastroenterology 2017年第41期23卷 7459-7469页

作者： Manuel Rodríguez Juan Manuel Pascasio Enrique Fraga Javier Fuentes martín prieto Gloria Sánchez-Antolín Jose Luis Calleja Esther Molina María Luisa García-Buey María Angeles Blanco Javier Salmerón María Lucía Bonet Jose Antonio Pons Jose Manuel González Miguel Angel Casado Francisco Jorquera 无 Division of Gastroenterology and Hepatology.Hospital Universitario Central de Asturias Unit for the Clinical Management of Digestive Diseases IBISHospital Universitario Virgen del Rocío Liver Transplantation and Hepatology Unit Gastroenterology ServiceHospital Universitario Reina Sofía Digestive Medicine Service Hospital Universitario Miguel Servet Hepatology Unit Digestive Medicine ServiceHospital Universitari i Politècnic La Fe Hepatology Unit Hospital Universitario Rio Hortega Liver Unit Hospital Universitario Puerta de Hierro de MajadahondaUniversidad Autónoma de Madrid Digestive Medicine Service Hospital Clínico de Santiago de Compostela Liver Unit Hospital Universitario de La Princesa Digestive Medicine Service Hospital General Universitario Gregorio Maranon Digestive Medicine Unit Complejo Hospitalario de Granada Digestive Medicine Service Hospital Universitario Son Espases Hepatology Unit IMIB Hospital Universitario Virgen de la Arrixaca Digestive Medicine Service Hospital Clínico Universitario de Valladolid Pharmacoeconomics and Outcomes Research Iberia Division of Gastroenterology and Hepatology Complejo Asistencial Universitario de León the TEnOSIMP-B Research Group

AIM To demonstrate the non-inferiority(15% non-inferiority limit) of monotherapy with tenofovir disoproxil fumarate(TDF) vs the combination of lamivudine(LAM) plus adefovir dipivoxil(ADV) in the maintenance of virologic response in patients with chronic hepatitis B(CHB) and prior failure with *** This study was a Phase IV prospective, randomized, open, controlled study with 2 parallel groups(TDF and LAM+ADV) of adult patients with hepatitis B e antigen(HBe Ag)-negative CHB, prior failure with LAM, on treatment with LAM+ADV for at least 6 mo, without prior resistance to ADV and with an undetectable viral load at the start of the study, in 14 Spanish hospitals. The follow-up time for each patient was 48 wk after randomization, with quarterly visits in which the viral load, biochemical and serological parameters, adverse effects, adherence to treatment and consumption of hospital resources were *** Forty-six patients were evaluated [median age: 55.4 years(30.2-75.2); 84.8% male], including 22 patients with TDF and 24 with LAM+ADV. During study development, hepatitis B virus DnA(HBV-DnA) remained undetectable, all patients remained HBe Ag negative, and hepatitis B surface antigen(HBs Ag) positive. Alanine aminotransferase(ALT) values at the end of the study were similar in the 2 groups(25.1± 7.65, TDF vs 24.22 ± 8.38, LAM+ADV, P = 0.646). no significant changes were observed in creatinine or serum phosphorus values in either group. no significant differences between the 2 groups were noted in the identification of adverse effects(AEs)(53.8%, TDF vs 37.5%, LAM+ADV, P = 0.170), and none of the AEs which occurred were serious. Treatment adherence was 95.5% and 83.3% in the TDF and the LAM+ADV groups, respectively(P = 0.488). The costs associated with hospital resource consumption were significantly lower with the TDF treatment than the LAM+ADV treatment(€4943 ± 1059 vs €5811 ± 1538, respectively, P nCLUSIOn TDF monotherapy proved to be safe

关键词： Tenofovir Lamivudine+Adefovir Efficacy Safety Adherence Costs Hepatitis B

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Post-translational modifications of prostaglandin-endoperoxide synthase 2 in colorectal cancer:An update

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World Journal of Gastroenterology 2018年第48期24卷 5454-5461页

作者： Rafael I Jaén Patricia prieto marta Casado Paloma martín-Sanz Lisardo Boscá Department of Metabolism and Physiopathology of Inflammatory Diseases Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) Department of Biomedicine Instituto de Biomedicina de Valencia (CSIC) Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares y Hepáticas y DigestivasISCⅢ Unidad Asociada IIBMULPGC Universidad de las Palmas de Gran Canaria (ULPGC)

The biosynthesis of prostanoids is involved in both physiological and pathological processes. The expression of prostaglandin-endoperoxide synthase 2(PTGS2; also known as COX-2) has been traditionally associated to the onset of several pathologies, from inflammation to cardiovascular, gastrointestinal and oncologic events. For this reason, the search of selective PTGS2 inhibitors has been a focus for therapeutic interventions. In addition to the classic non-steroidal anti-inflammatory drugs, selective and specific PTGS2 inhibitors, termed coxibs, have been generated and widely used. PTGS2 activity is less restrictive in terms of substrate specificity than the homeostatic counterpart PTGS1, and it accounts for the elevated prostanoid synthesis that accompanies several pathologies. The main regulation of PTGS2 occurs at the transcription level. In addition to this, the stability of the mRnA is finely regulated through the interaction with several cytoplasmic elements, ranging from specificmicroR nAs to proteins that control mR nA degradation. Moreover, the protein has been recognized to be the substrate for several post-translational modifications that affect both the enzyme activity and the targeting for degradation via proteasomal and non-proteasomal mechanisms. Among these modifications, phosphorylation, glycosylation and covalent modifications by reactive lipidic intermediates and by free radicals associated to the proinflammatory condition appear to be the main changes. Identification of these post-translational modifications is relevant to better understand the role of PTGS2 in several pathologies and to establish a correct analysis of the potential function of this protein in diseases progress. Finally, these modifications can be used as biomarkers to establish correlations with other parameters, including the immunomodulation dependent on molecular pathological epidemiology determinants, which may provide a better frame for potential therapeutic interventions.

关键词： Prostaglandins Prostaglandin-endoperoxide synthase 2 Post-translational modifications Glycosylation Colorectal cancer Inflammation

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Interplay between post-translational cyclooxygenase-2 modifications and the metabolic and proteomic profile in a colorectal cancer cohort

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World Journal of Gastroenterology 2019年第4期25卷 433-446页

作者： Patricia prieto Rafael I Jaén Daniel Calle María Gómez-Serrano Estefanía nú?ez María Fernández-Velasco Paloma martín-Sanz Sergio Alonso Jesús Vázquez Sebastián Cerdán Miguel ángel Peinado Lisardo Boscá Department of Metabolism and Physiopathology of Inflammatory Diseases Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (Ciber-CV) Instituto de Salud Carlos III (ISCIII) Laboratorio de Imagen Médica Hospital Universitario Gregorio Mara?ón Laboratorio de Proteómica Cardiovascular Centro Nacional de Investigaciones Cardiovasculares (CNIC) Instituto de Investigación Sanitaria del Hospital Universitario la Paz(IdiPaz) Programa de Medicina Predictiva y Personalizada del Cáncer (PMPPC) Fundación Instituto de investigación en ciencias de la salud Germans Trias i PujolCtra Can Ruti

BACKGROUnD Colorectal cancer(CRC) is the second most common cause of cancer death worldwide. It is broadly described that cyclooxygenase-2(COX-2) is mainly overexpressed in CRC but less is known regarding post-translational modifications of this enzyme that may regulate its activity, intracellular localization and stability. Since metabolic and proteomic profile analysis is essential for cancer prognosis and diagnosis, our hypothesis is that the analysis of correlations between these specific parameters and COX-2 state in tumors of a high number of CRC patients could be useful for the understanding of the basis of this cancer in *** To analyze COX-2 regulation in colorectal cancer and to perform a detailed analysis of their metabolic and proteomic *** Biopsies from both healthy and pathological colorectal tissues were taken under informed consent from patients during standard colonoscopy procedure in the University Hospital of Bellvitge(Barcelona, Spain) and Germans Trias i Pujol University Hospital(Campus Can Ruti)(Barcelona, Spain). Western blot analysis was used to determine COX-2 levels. Deglycosylation assays were performed in both cells and tumor samples incubating each sample with peptide n-glycosidase F(PnGase F). Prostaglandin E2(PGE2) levels were determined using a specific ELISA. 1 H high resolution magic angle spinning(HRMAS) analysis was performed using a Bruker AVIII 500 MHz spectrometer and proteomic analysis was performed in a nano-liquid chromatography-tandem mass spectrometer(nano LC-MS/MS) using a QExactive HF orbitrap *** Our data show that COX-2 has a differential expression profile in tumor tissue of CRC patients vs the adjacent non-tumor area, which correspond to a glycosylated and less active state of the protein. This fact was associated to a lesser PGE2 production in tumors. These results were corroborated in vitro performing deglycosylation assays in HT29 cell line where COX-2 protein profile was modified after Pn

关键词： Colon Carcinoma Cyclooxygenase Prostaglandin Proteomics High resolution magic angle spinning

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Adipokines,cytokines and body fat stores in hepatitis Cvirus liver steatosis

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World Journal of Hepatology 2016年第1期8卷 74-82页

作者： emilio gonzález-reimers javier lópez-prieto geraldine quintero-platt ricardo pelazas-gonzález m remedios alemán-valls onán pérez-hernández m joséde-la-vega-prieto m angeles gómez-rodríguez candelaria martín-gonzález francisco santolaria-fernández Servicio de Medicina Interna Hospital Universitario de CanariasUniversidad de La Laguna38320 Canary IslandsSpain

AIM: To identify patients with or without liver steatosis and its severity in treatment-na?ve patients affected by hepatitis C virus(HCV) ***: We included 56 HCV infected patients, and assessed the amount of liver fat by histomorphometry, and its relationships with fat and lean mass at different parts of the body(by densitometry), hormones [insulin, homeostatic model assessment(HOMA)], adipokines(resistin, adiponectin, leptin), and cytokines(tumor necrosis factor α, interleukin-6).RESULTS: Although the intensity of liver steatosis is related to trunk fat mass and HOMA, 33% of patients showed no liver steatosis, and this finding was not related to body mass index or genotype. Besides trunkfat mass, no other factor was related to the presence or not of liver steatosis, or to the intensity of it, by multivariate analysis. Lean mass was not related to liver steatosis. Adiponectin levels were lower among patients. no differences were observed in leptin and ***: Steatosis in HCV infection is common(67.2%), and closely related to trunk fat, and insulin resistance, but not with leg fat mass or adipokines.

关键词： Resistin Adiponectin Insulin resistance Proinflammatory cytokines Leptin Hepatitis C virus Liver steatosis

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Mechanical properties of the A356 aluminum alloy modified with La/Ce

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Journal of Rare Earths 2013年第8期31卷 811-816页

作者： E. Aguirre-De la Torre R. Pérez-Bustamante J. Camarillo-Cisneros C.D. Gómez-Esparza H.M. Medrano-prieto R. martínez-Sánchez Advanced Materials Research Center (CIMAV) National Laboratory of Nanotechnology

The research of rare earths for the synthesis of materials with improved mechanical performance is of great interest when they are considered for potential applications in the automotive industry. In this regard, the effect on the mechanical properties and microstmcture of the automotive A356 aluminum alloy reinforced with 0.2 （wt.%） AI-6Ce-3La （ACL） was investigated. The ACL was added to the melted A356 alloy in the as-received condition and processed by mechanical milling. In the second route, the effect of the ACL processed by mechanical milling and powder metallurgy techniques was investigated, and compared with the results ob- tained from the A356 alloy strengthened with ACL in the as-received condition. Microstmctural properties were evaluated by means of X-ray diffraction in order to observe the solubility of Ce/La in the A1 matrix. In addition, electron microscopy was employed in or- der to investigate the effect of milling time on the size and morphology of La/Ce phase under milling process. Mechanical properties of the A356 alloy modified with ACL were measured by hardness and tensile test. For comparison unmodified specimens of the A356 were characterized according to the previous procedure. The microstructural and mechanical characterization was carried out in specimens alter solution and artificial aging. Observations in scanning electron microscopy indicated a homogeneous dispersion of La/Ce phases by using both routes; however, mechanical results, in the modified A356 alloy with the ACL in the as-received condi- tion, showed an improvement in the mechanical performance of the A356 alloy over that reinforced with the ACL mechanically milled.

关键词： A356 rare earths mechanical milling mechanical properties

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Capsule endoscopy capture rate: Has 4 frames-per-second any impact over 2frames-per-second?

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World Journal of Gastroenterology 2014年第39期20卷 14472-14478页

作者： Ignacio Fernandez-Urien Cristina Carretero Erika Borobio Ana Borda Emilio Estevez Sara Galter Begoa Gonzalez-Suarez Benito Gonzalez Marisol Lujan Jose Luis martinez Vanessa martínez Pedro Menchén Javier navajas Vicente Pons Cesar prieto Julio Valle Department of Gastroenterology Hospital de Navarra 31008 Pamplona Spain Department of Gastroenterology Clínica Universidad de Navarra 31008 Pamplona Spain Department of Gastroenterology Hospital Juan Canalejo 26131 La Coru?a Spain Department of Gastroenterology Hospital de Tarrasa 08509 Barcelona Spain Department of Gastroenterology Hospital del Mar 08509 Barcelona Spain Department of Gastroenterology Hospital General de Valencia 46367 Valencia Spain Department of Gastroenterology Hospital Puerta de Hierro 28816 Madrid Spain Department of Gastroenterology Hospital La Fe 46367 Valencia Spain Department of Gastroenterology Hospital Gregorio Mara?ón 28816 Madrid Spain Department of Gastroenterology Complejo Hospitalario de Toledo 45591 Toledo Spain

AIM: To compare the current capsule and a new prototype at 2 and 4 frames-per-second, respectively, in terms of clinical and therapeutic impact.

关键词： Capsule endoscopy Small bowel Diagnostic accuracy Frames Lesions Landmarks

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About One-Dimensional Conservative Systems with Position Depending Mass

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Journal of Modern Physics 2014年第9期5卷 900-907页

作者： Gustavo López Velázquez Carlos Rodrigo martínez prieto Departamento de Fsica Universidad de Guadalajara Guadalajara México Instituto Tecnológico y Estudios Superiores de Occidente Tlaquepaque México

For a one-dimensional conservative system with position depending mass, one deduces consistently a constant of motion, a Lagrangian, and a Hamiltonian for the nonrelativistic case. With these functions, one shows the trajectories on the spaces (x,v) and (x,p) for a linear position depending mass. For the relativistic case, the Lagrangian and Hamiltonian cannot be given explicitly in general. However, we study the particular system with constant force and mass linear dependence on the position where the Lagrangian can be found explicitly, but the Hamiltonian remains implicit in the constant of motion.

关键词： Mass Variable Systems Conservative System Position Depending Mass

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About an Ambiguity Appearing on the Hamiltonian Formulation of Quantum Mechanics

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Journal of Applied Mathematics and Physics 2018年第6期6卷 1382-1387页

作者： Gustavo V. López Ana Griselda Carlos R. martínez-prieto Departamento de Física Universidad de Guadalajara Guadalajara Mexico

We study classical and quantum dynamics of the symmetric harmonic oscillator and the symmetric bouncer defined in 2-D. For these systems we get each of them for two different constants of motion, two Lagrangians and two Hamiltonians which describe the same classical dynamics. However, the quantization of these systems (using Schrödinger equation), using their two equivalents Hamiltonian, describes different quantum dynamics for each of them. This represents an ambiguity on the Hamiltonian formulation of the Quantum Mechanics.

关键词： Harmonic Oscillator Quantum Bouncer Ambiguities in Quantum Mechanics Theory

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Low serum levels of ghrelin are associated with gallstone disease

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World Journal of Gastroenterology 2006年第19期12卷 3096-3100页

作者： nahum Méndez-Sánchez Guadalupe Ponciano-Rodríguez Luisa Bermejo-martínez Antonio R Villa norberto C Chávez-Tapia Daniel Zamora-Valdés Raúl Pichardo-Bahena Blanca Barredo-prieto martha H Uribe-Ramos martha H Ramos Héctor A Baptista-González Misael Uribe Liver Unit Biomedical Research Department Medica Sur Clinic and FoundationMexico CityMexico Faculty of Medicine national Autonomous University of Mexico (UnAM) Mexico CityMexico Clinical Research Department national Institute of Perinatology Mexico CityMexico Clinical Epidemiology Unit national Institute of Medical Sciences and nutrition Mexico CityMexico

AIM： To explore the role of ghrelin in gallstone disease. METHODS： We carried out a cross-sectional study in 150 subjects, 38 with gallstones （cases） and 112 controls. We also did a real-time PCR-RT study in twenty gallbladder samples each. Body mass index （BnI）, serum insulin, ghrelin, and serum lipids were measured. Logistic regression analyses （univariate and multivariate） were conducted to estimate the probability of gallstone disease associated with serum ghrelin concentrations. RESULTS： Cases were statistically different from controls in gender distribution （P = 0.01）, age （53 vs 44 yr, P = 0.002）, BnI （28 vs 25; P = 0.004）, and glucose （5.26 vs 4.98 mmol/L; P = 0.05）. The prevalence of ghrelin serum levels above the third tercile was lower in subjects without metabolic syndrome （P 〈 0.05）. In a multivariate model, we found a protective effect, when ghrelin values were higher than the median value （OR = 0.27, 95%CI 0.09-0.82, P = 0.02）. Twenty （20%） gallbladder specimens expressed ghrelin mRnA. COnCLUSIOn： Serum ghrelin concentrations are associated with a protective effect of GD.

关键词： Gallstones Obesity Ghrelin Gallbladder Gastrointestinal hormones

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Physical Mathematical Evaluation of the Cardiac Dynamic Applying the Zipf-Mandelbrot Law

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Journal of Modern Physics 2015年第13期6卷 1881-1888页

作者： Javier Oswaldo Rodríguez Signed Esperanza prieto Sandra Catalina Correa Fernán Mendoza Giora Weiz María Yolanda Soracipa nelly Velásquez Juan Mauricio Pardo Miguel martínez Freddy Barrios Insight Research Group Bogotá Colombia Clínica del Country Research Center Bogotá Colombia Fundación Clínica Abood Shaio Bogotá Colombia Universidad el Bosque Bogotá Colombia Columbia University Medical Center Cardiology Shaare Zedek Medical Center Jerusalem Israel Hospital Universitario Mayor Méderi Bogotá Colombia Physiology Medicine Faculty Universidad Nacional de Colombia Bogotá Colombia

Introduction: The law of Zipf-Mandelbrot is a power law, which has been observed in natural languages. A mathematical diagnosis of fetal cardiac dynamics has been developed with this law. Objective: To develop a methodology for diagnostic aid to assess the degree of complexity of adult cardiac dynamics by Zipf-Mandelbrot law. Methodology: A mathematical induction was done for this;two groups of Holter recordings were selected: 11 with normal diagnosis and 11 with acute disease of each group, one Holter of each group was chosen for the induction, the law of Zipf-Mandelbrot was applied to evaluate the degree of complexity of each Holter, searching similarities or differences between the dynamics. A blind study was done with 20 Holters calculating sensitivity, specificity and the coefficient kappa. Results: The complexity grade of a normal cardiac dynamics varied between 0.9483 and 0.7046, and for an acute dynamic between 0.6707 and 0.4228. Conclusions: A new physical mathematical methodology for diagnostic aid was developed;it showed that the degree of complexity of normal cardiac dynamics was higher than those with acute disease, showing quantitatively how cardiac dynamics can evolve to acute state.

关键词： Heart Rate Cardiovascular Diseases Zipf-Mandelbrot Law Complexity Grade

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