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Impact of STAT-signaling pathway on cancer-associated fibroblasts in colorectal cancer and its role in immunosuppression

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1705-1724页

作者： Damián Sánchez-Ramírez Mónica G Mendoza-Rodríguez Omar R Alemán Fernando A Candanedo-González Miriam Rodríguez-Sosa Juan JoséMontesinos-Montesinos Mauricio Salcedo Ismael Brito-Toledo Felipe Vaca-Paniagua Luis I Terrazas Unidad de Investigacion en Biomedicina Facultad de Estudios Superiores IztacalaUniversidad Nacional Autonoma de MexicoTlalnepantla 54090Estado de MexicoMexico department of Biology Facultad de QuimicaUniversidad Nacional Autonoma de MexicoCiudad UniversitariaMexico City 04510Mexico department of Pathology National Medical Center Century XXIInstituto Mexicano del Seguro SocialMexico City 06720Mexico Laboratorio de Células Troncales Mesenquimales Unidad de Investigación Médica en Enfermedades OncológicasHospital de Oncología Centro Medico Nacional Siglo XXIInstituto Mexicano del Seguro SocialMexico City 06720Mexico Unidad de Investigacion en Biomedicina y Oncologia Genomica Instituto Mexciano del Seguro SocialMexico City 07300Mexico Servicio de Colon y Recto Hospital de Oncología Centro Medico Nacional Siglo XXIInstituto Mexicano del Seguro SocialMexico City 06720Mexico Laboratorio Nacional en salud Facultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla 54090Estado de MexicoMexico

Colorectal cancer(CRC)remains one of the most commonly diagnosed and deadliest types of cancer worldwide.CRC displays a desmoplastic reaction(DR)that has been inversely associated with poor prognosis;less DR is associated with a better prognosis.This reaction generates excessive connective tissue,in which cancer-associated fibroblasts(CAFs)are critical cells that form a part of the tumor microenvironment.CAFs are directly involved in tumorigenesis through different mechanisms.However,their role in immunosuppression in CRC is not well understood,and the precise role of signal transducers and activators of transcription(STATs)in mediating CAF activity in CRC remains unclear.Among the myriad chemical and biological factors that affect CAFs,different cytokines mediate their function by activating STAT signaling pathways.Thus,the harmful effects of CAFs in favoring tumor growth and invasion may be modulated using STAT inhibitors.Here,we analyze the impact of different STATs on CAF activity and their immunoregulatory role.

关键词： Cancer-associated fibroblasts Signal transducer and activator of transcription signaling Colorectal cancer Immunity Immunosuppression

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Novel insights into D-Pinitol based therapies:a link between tau hyperphosphorylation and insulin resistance

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Neural Regeneration Research 2024年第2期19卷 289-295页

作者： Dina Medina-Vera Antonio Jesús López-Gambero Juan Antonio Navarro Carlos Sanjuan Elena Baixeras Juan decara Fernando Rodríguez de Fonseca Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND UGC Salud MentalMálagaSpain Facultad de Ciencias Universidad de MálagaMálagaSpain CIBER enfermedades Cardiovasculares(CIBERCV) Hospital Universitario Virgen de la VictoriaUGC del CorazónMálagaSpain University of Bordeaux INSERMNeurocentre MagendieBordeauxFrance Euronutra S.L.Calle Johannes Kepler MálagaSpain departamento de Bioquímica y Biología Molecular Facultad de MedicinaUniversidad de MálagaMálagaSpain

Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.

关键词： Alzheimer’s disease cyclin-dependent kinase 5 diabetes D-Pinitol inositols insulin resistance kinases phosphorylation PI3K/Akt tau

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Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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Neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón Pérez-Núñez María Fernanda González Ana María Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

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Association between lifestyle factors and thyroid function in young euthyroid adults

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Food Science and Human Wellness 2024年第1期13卷 265-275页

作者： Elisa Merchan-Ramirez Guillermo Sanchez-delgado Lucas Jurado-Fasoli Francisco M Acosta Manuel Munoz-Torres Jose M.Llamas-Elvira Jonatan R Ruiz Sport and Health University Research Institute(iMUDS) Faculty of Sports ScienceUniversity of GranadaGranada 18016Spain Pennington Biomedical Research Center Baton Rouge 70808USA Faculty of Medicine University of GranadaGranada 18071Spain Turku PET Centre University of TurkuTurku 20500Finland Turku PET Centre Turku University HospitalTurku 20520Finland Biosanitary Research Institute of Granada(Ibs.Granada) Granada 18012Spain CIBERFES Instituto de Salud CarlosⅢMadrid 28029Spain endocrinology and Nutrition Service University Hospital San CecilioGranada 18016Spain Nuclear Medicine Service "Virgen de las Nieves"University HospitalGranada 18014Spain

Purpose:The present work examines the associations of dietary habits,sedentarism,physical activity(PA)levels and sleep habits,with thyroid function in young euthyroid adults.Methods:A total of 105 young euthyroid adults participated in this cross-sectional study.Thyroid function was determined in fasting conditions(>6 h).Dietary habits were measured by a food frequency questionnaire and three non-consecutive 24 h recalls,and different dietary intake and patterns were then estimated.The time spent in sedentary,PA levels and sleep habits were objectively measured using a wrist-worn accelerometer.Results:energy and carbohydrate intake were positively associated with thyroid stimulating hormone(TSH)(β=0.222;R^(2)=0.102;P=0.022 andβ=0.425;R^(2)=0.129;P=0.007,respectively)whereas fat intake was negatively associated with TSH(β=-0.428;R^(2)=0.137;P=0.004).energy intake was also positively associated with free triiodothyronine(β=0.277;R^(2)=0.137;P=0.004).Further,adherence to the Mediterranean diet was negatively related to TSH and free thyroxine(FT4)(β=-0.221;R^(2)=0.113;P=0.020 andβ=-0.268;R^(2)=0.071;P=0.007,respectively).Vigorous-intensity and overall PA were negatively associated with FT4(β=-0.227;R^(2)=0.052;P=0.022 andβ=-0.204;R^(2)=0.042;P=0.041,respectively).In contrast,no associations were found between sleep parameters and thyroid function.Conclusions:Lifestyle factors such as dietary intake and PA levels seems to be related to thyroid function even in young euthyroid adults.

关键词： Thyroid hormones Dietary intake Sleep Physical activity Euthyroid

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Mutated trimeric RBD vaccines:a platform against variants of concern

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2038-2040页

作者： Belén Aparicio Juan J.Lasarte Pablo Sarobe programa de Inmunología e Inmunoterapia Centro de Investigación Médica Aplicada(CIMACCUN)Universidad de NavarraPamplona31008Spain Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas(CIBEREHD) Pamplona31008Spain IdiSNA Instituto de Investigación Sanitaria de NavarraPamplona31008Spain

He et al.recently reported in Nature Communications1 the development of a protein vaccine against SASR-CoV-2 Omicron variant consisting of a trimer of the spike protein receptor-binding domain(RBD)of the delta variant fused to heptad-repeat sequences 1 and 2.This vaccine induced broad-spectrum neutralizing antibodies and fully protected mice and non-human primates against challenge with live delta and Omicron virus.

关键词： vaccine vaccines

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The Acute and Chronic Effects of Co-Administration of Turmeric and Black Pepper Extracts in Genetic Hypertension

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Journal of Biosciences and Medicines 2023年第8期11卷 114-128页

作者： Ma. Guadalupe Calderón-Gallardo Lilia Castillo-Martínez Samuel Estrada-Soto Itzell A. Gallardo-Ortíz Rafael Villalobos-Molina Unidad de Biomedicina Facultad de Estudios Superiores Iztacala Universidad Nacional Autónoma de México Tlalnepantla México programa de Maestría y Doctorado en Ciencias Médicas Odontológicas y de la Salud Doctorado en Investigación Clínica Experimental en Salud Universidad Nacional Autónoma de México Ciudad de México México Instituto Nacional de Nutrición Salvador Zubirán Ciudad de México México Facultad de Farmacia Universidad Autónoma del Estado de Morelos Cuernavaca México

High blood pressure is the main risk factor for cardiovascular diseases, it affects many people worldwide and is a public health problem. This study explored the acute and chronic actions of a mixture of turmeric (95% curcumin) plus black pepper (95% piperine) extracts, in the blood pressure pattern in spontaneously hypertensive rats (SHR) along they age. For the acute study male adult (4 - 7 months old) SHR and their control Wistar Kyoto rats (WKY) were used. A single oral dose of the mixture of turmeric/black pepper extracts (200 mg/2mg, respectively) suspension was administered. Tail-cuff was used to determine blood pressure during 180 min. For the chronic study, young (1-month-old) male SHR and their control WKY rats were fed with standard chow, or standard chow combined with cocoa, or combined with cocoa plus the mixture of turmeric/black pepper extracts;tail-cuff was used to determine blood pressure once a week, along 12 weeks. In a second chronic assay adult (5 months old) male SHR and their control WKY rats were fed with standard chow, or standard chow combined with cocoa, or combined with cocoa plus the mixture of turmeric/black pepper extracts;tail-cuff was used to determine blood pressure once a week, along 12 weeks. In all three studies, a decrease in systolic, diastolic and mean blood pressure was observed, being higher in SHR and negligible in WKY rats. The mixture of turmeric/black pepper extracts showed antihypertensive actions in SHR rats with no effect on WKY rats. The mixture delayed the onset of hypertension in young SHR rats.

关键词： Curcuma longa L. Peper nigrum L. Hypertension Polyphenol SHR

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Submicroscopic 11p13 deletion including the elongator acetyltransferase complex subunit 4 gene in a girl with language failure, intellectual disability and congenital malformations: A case report

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World Journal of Clinical Cases 2020年第21期8卷 5296-5303页

作者： Jaime Toral-Lopez Luz María González Huerta Olga Messina-Baas Sergio A Cuevas-Covarrubias departamento de Genética Medica Centro Medico EcatepecISSEMYMEcatepec 55000México programa de Maestría y Doctorado en Ciencias Médicas Odontológicas y de la Salud/Hospital Infantil de MéxicoUniversidad Nacional Autónoma de MéxicoMéxico 06720México departamento de Biología Molecular Hospital General de MéxicoCuauhtémoc 06720México departamento de Oftalmología Hospital General de MéxicoCuauhtémoc 06720México Genetica Hospital General de MéxicoCuauhtémoc 06726Mexico Sergio A Cuevas-CovarrubiasPrograma de Maestría y Doctorado en Ciencias MédicasOdontológicas y de la SaludUniversidad Nacional Autónoma de MéxicoMéxico 06720Mexico

BACKGROUND We described the main features of an infant diagnosed with facial dysmorphic,language failure,intellectual disability and congenital malformations to strengthen our understanding of the disease.Currently,treatment is only rehabilitation and surgery for cleft lip and palate.CASE SUMMARY The proband was a 2-years-8-months-old girl.Familial history was negative for congenital malformations or intellectual disability.The patient had microcephaly,upward-slanting palpebral fissures,depressed nasal bridge,bulbous nose and bilateral cleft lip and palate.Brain magnetic resonance imaging showed cortical atrophy and band heterotopia.Her motor and intellectual development is delayed.A submicroscopic deletion in 11p13 involving the elongator acetyltransferase complex subunit 4 gene(ELP4)and a loss of heterozygosity in Xq25-q26.3 were detected.CONCLUSION There is no treatment for the ELP4 deletion caused by a submicroscopic 11p3 deletion.We describe a second case of deletion of the ELP4 gene without aniridia,which confirms the association between ELP4 gene with several defects and absence of this ocular defect.Additional clinical data in the deletion of the ELP4 gene as cleft palate,facial dysmorphism,and changes at level brain could be associated to this gene or be part of the effect of the recessives genes involved in the loss of heterozygosity region of Xq25-26.3.

关键词： Submicroscopic 11p13 deletion Elongator acetyltransferase complex subunit 4 gene Language failure Intellectual disability Congenital malformations Case report

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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 humans.AIM To analyze COX-2 regulation in colorectal cancer and to perform a detailed analysis of their metabolic and proteomic profile.METHODS 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 MS.RESULTS 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 PNGase F incubation, showing higher PGE2 levels. M

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

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Role of copper nanoparticles in wound healing for chronic wounds:literature review

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Burns & Trauma 2022年第1期10卷 805-813页

作者： Jessica Salvo Cristian Sandoval Escuela de enfermería Facultad de CienciasUniversidad MayorChile programa de Doctorado en Ciencias Morfológicas Facultad de MedicinaUniversidad de la FronteraAv.Francisco Salazar 011454811230TemucoChile Escuela de Tecnología Médica Facultad de SaludUniversidad Santo TomásLos Carreras 7535310431OsornoChile departamento de Ciencias Preclínicas Facultad de MedicinaUniversidad de la FronteraAv.Francisco Salazar 011454811230TemucoChile

Chronic wounds are defined as wounds that fail to proceed through the normal phases of wound healing in an orderly and timely manner.The most common and inevitable impairment to wound healing is the installation of an infection,usually in the case of chronic wounds.Therefore,the objective of the present review was to identify the importance of copper nanoparticles in dressings for wound healing.Nanoparticles such as silver,gold and copper combat infectious processes through the inhibition of protein synthesis,peroxidation of the cell membrane and destroying the nucleic acids of bacteria and viruses.Among bioactive nanoparticles,copper plays a complex role in various cells,it modulates several cytokines and growth factor mechanisms of action and is essentially involved in all stages of the wound healing process.More importantly,copper plays a key role in skin regeneration and angiogenesis and accelerates the healing process through induction of vascular endothelial growth factor(VEGF)and angiogenesis by hypoxia-induced factor-1-alpha(HIF-1α)action where copper enhances HIF-1αexpression and HIF-1αbinding to the critical motifs in the promoter and putative enhancer regions of HIF-1-regulated genes.

关键词： Angiogenesis Antimicrobial Nanoparticles Regeneration Wound healing Chronic wound VEGF HIF-1α

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Management of Helicobacter pylori infection in Latin America: A delphi technique-based consensus

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World Journal of Gastroenterology 2014年第31期20卷 10969-10983页

作者： Antonio Rollan Juan Pablo Arab M Constanza Camargo Roberto Candia Paul Harris Catterina Ferreccio Charles S Rabkin Juan Cristóbal Gana Pablo Cortés Rolando Herrero Luisa Durán Apolinaria García Claudio Toledo Alberto Espino Nicole Lustig Alberto Sarfatis Catalina Figueroa Javier Torres Arnoldo Riquelme Clínica Alemana de Santiago Facultad de Medicina Clínica Alemana Universidad del Desarrollo departamento de Gastroenterología Facultad de Medicina Pontificia Universidad Católica de Chile Division of Cancer Epidemiology and Genetics National Cancer InstituteRockville MD 20852 United States Programa de Salud Basada en Evidencia Pontificia Universidad Católica de Chile departamento de Gastroenterología y Nutrición Pediátrica Facultad de Medicina Pontificia Universidad Católica de Chile departamento de salud Pública Facultad de Medicina Pontificia Universidad Católica de Chile International Agency for Research on Cancer World Health Organization departamento de Microbiología Facultad de Ciencias Biológicas Universidad de Concepción Unidad de Gastroenterología Hospital de Valdivia. Facultad de Medicina Universidad de Austral de Chile Unidad de Investigación en enfermedades Infecciosas Instituto Mexicano del Seguro Social

AIM: To optimize diagnosis and treatment guidelines for this geographic region, a panel of gastroenterologists, epidemiologists, and basic scientists carried out a structured evaluation of available literature.METHODS: Relevant questions were distributed among the experts, who generated draft statements for consideration by the entire panel. A modified three-round delphi technique method was used to reach consensus. Critical input was also obtained from representatives of the concerned medical community. The quality of the evidence and level of recommendation supporting each statement was graded according to United States Preventive Services Task Force criteria.RESULTS: A group of ten experts was established. The survey included 15 open-ended questions that were distributed among the experts, who assessed the articles associated with each question. The levels of agreement achieved by the panel were 50% in the first round, 73.3% in the second round and 100% in the third round. Main consensus recommendations included:(1) when available, urea breath and stool antigen test(HpSA) should be used for non-invasive diagnosis;(2) detect and eradicate Helicobacter pylori(H. pylori) in all gastroscopy patients to decrease risk of peptic ulcer disease, prevent o retard progression in patients with preneoplastic lesions, and to prevent recurrence in patients treated for gastric cancer;(3) further investigate implementation issues and health outcomes of H. pylorieradication for primary prevention of gastric cancer in high-risk populations;(4) prescribe standard 14-d triple therapy or sequential therapy for first-line treatment;(5) routinely assess eradication success post-treatment in clinical settings; and(6) select second- and third-line therapies according to antibiotic susceptibility testing.CONCLUSION: These achievable steps toward better region-specific management can be expected to improve clinical health outcomes.

关键词： Helicobacter pylori Consensus development conferen

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