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Liquid biopsy for gastric cancer:Techniques,applications,and future directions

World Journal of Gastroenterology 2024年第12期30卷 1680-1705页

作者： Cristina Díaz del Arco M Jesús Fernández Aceñero Luis Ortega Medina Department of Surgical Pathology Health Research Institute of the Hospital Clínico San CarlosHospital Clínico San CarlosMadrid 28040Spain Department of Legal Medicine Psychiatry and PathologyUniversidad Complutense de MadridMadrid 28040Spain

After the study of circulating tumor cells in blood through liquid biopsy(LB),this technique has evolved to encompass the analysis of multiple materials originating from the tumor,such as nucleic acids,extracellular vesicles,tumor-educated platelets,and other metabolites.Additionally,research has extended to include the examination of samples other than blood or plasma,such as saliva,gastric juice,urine,or stool.LB techniques are diverse,intricate,and variable.They must be highly sensitive,and pre-analytical,patient,and tumor-related factors significantly influence the detection threshold,diagnostic method selection,and potential results.Consequently,the implementation of LB in clinical practice still faces several challenges.The potential applications of LB range from early cancer detection to guiding targeted therapy or immunotherapy in both early and advanced cancer cases,monitoring treatment response,early identification of relapses,or assessing patient risk.On the other hand,gastric cancer(GC)is a disease often diagnosed at advanced stages.Despite recent advances in molecular understanding,the currently available treatment options have not substantially improved the prognosis for many of these patients.The application of LB in GC could be highly valuable as a non-invasive method for early diagnosis and for enhancing the management and outcomes of these patients.In this comprehensive review,from a pathologist’s perspective,we provide an overview of the main options available in LB,delve into the fundamental principles of the most studied techniques,explore the potential utility of LB application in the context of GC,and address the obstacles that need to be overcome in the future to make this innovative technique a game-changer in cancer diagnosis and treatment within clinical practice.

关键词： Liquid biopsy Gastric cancer Circulating tumor cells Cell-free DNA Circulating tumor DNA Molecular

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Carbocysteine as Adjuvant Therapy in Acute Respiratory Tract Infections in Patients without Underlying Chronic Conditions: Systematic Review and Meta-Analysis

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Open Journal of Respiratory Diseases 2024年第2期14卷 39-50页

作者： Myriam Calle Rubio Olga de la Serna Blazquez José Luis R. Martin Manuel Ruiz Cuetos Pulmonology Department Hospital Clínico San Carlos Madrid Spain Department of Medicine School of Medicine Universidad Complutense de Madrid Madrid Spain Instituto de Investigacion sanitaria del hospital clínico san carlos (IdISSC) Madrid Spain Pediatric Pulmonology Unit Pediatrics Department Hospital Universitario La Paz Madrid Spain Simplifying Research Institute Layos Spain Medical department in ITF Research Pharma S.L.U. Alcobendas Spain

Objective: This study aims to systematically examine the existing evidence regarding the clinical benefits of carbocysteine as an adjunctive treatment in acute bronchopulmonary and otorhinological processes. Design: Systematic review and meta-analysis. Data sources: An electronic search was conducted across PubMed, Cochrane Library, clinicaltrials.gov, and the European clinical Trial Register, with the search dated to May 2023. Bibliographic references from other literature reviews and meta-analyses were also reviewed. The search was limited to randomized clinical trials published in any language and year. It was completed by cross-checking the references of the located articles. Methods: Inclusion criteria covered studies assessing systemic or inhaled carbocysteine, regardless of dosing regimen. Concomitant medication use was acceptable if balanced between intervention and control groups. Authors independently extracted data, resolving disagreements through consensus. Methodological quality assessment relied on critical reading of each study. Dichotomous variables were analyzed using odds ratio (OR), and a final effect size was calculated. Statistical significance was established when confidence intervals did not cross the neutral value. Heterogeneity was assessed via the X2 test and I2 index. Results: Out of 318 initially identified studies, 4 met inclusion criteria. The meta-analysis for poor general condition yielded an OR of 0.45 in favor of intervention, p = 0.013, with non-significant heterogeneity. Cough events showed a percentage of 15.8% for carbocysteine vs. 27.2% for placebo. On the seventh day, expectoration rates were 18.37% for carbocysteinevs 33.3% for placebo. Conclusions: The observed clinical benefits align with carbocysteine’s mucoactive and muco-regulatory properties, complemented by anti-inflammatory and antioxidant actions. Carbocysteine stands out among mucolytic agents. In the context of persistent infectious diseases, the study emphasizes the need for further explor

关键词： Acute Respiratory Infections Carbocystenine Systematic Review Meta-Analysis

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Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1166-1179页

作者： Sebastián Díaz-López Jerónimo Jiménez-Castro carlos Enrique Robles-Barraza carlos Ayala-de Miguel Manuel Chaves-Conde Medical Oncology Department Hospital Universitario ValmeSeville 41014AndalucíaSpain

Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are a hetero-geneous group of malignant neoplasms that can settle in the gastroenteropan-creatic tract.They are composed of a neuroendocrine(NE)and a non-NE compo-nent in at least 30%of each tumour.The non-NE component can include different histological combinations of glandular,squamous,mucinous and sarcomatoid phenotypes,and one or both of the components can be low-or high grade malignant.Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion,and the lack of specific clinical trials is the main reason why their management is difficult.The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data.It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that,due to their low incidence,will require long recruitment periods.

关键词： Mixed neuroendocrine non-neuroendocrine neoplasms Mixed adenoneuroendocrine carcinomas Mixed tumours Gastroenteropancreatic Treatment Etiology Diagnosis

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Intense pulsed light‑based treatment for the improvement of symptoms in glaucoma patients treated with hypotensive eye drops

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Eye and Vision 2024年第2期10卷 12-21页

作者： Jose Maria Martinez‑de‑la‑Casa carlos Oribio‑Quinto Almudena Milans‑del‑Bosch Pilar Perez‑Garcia Laura Morales‑Fernandez Javier Garcia‑Bella Jose Manuel Benitez‑del‑Castillo Julian Garcia‑Feijoo David P.Pinero Ophthalmology Unit Department of Ophthalmology and ORLFaculty of MedicineHospital Clinico San-CarlosUniversidad Complutense de MadridInstituto de Investigacion Sanitaria del Hospital Clinico San-Carlos(IdISSC)28040 MadridSpain Department of Immunology Ophthalmology and ORLSchool of MedicineInstituto de Investigaciones Oftalmologicas Ramon CastroviejoUniversidad Complutense de MadridMadridSpain Department of Optics Pharmacology and AnatomyUniversity of AlicanteAlicanteSpain

Background:Ocular surface disease in glaucoma patients is a significant ocular co-morbidity that can affect 40%to 59%of these patients worldwide.The current study was aimed at evaluating the potential clinical benefit of an intense pulsed light(IPL)-based treatment in glaucomatous patients with ocular surface disease due to prolonged hypotensive eyedrop treatments.To our knowledge,this is the first series analyzing the therapeutic effect of this treatment option in this type of patients.Methods:This non-comparative prospective case series study enrolled a total of 30 glaucoma patients ranging in age from 57 to 94 years old and treated with hypotensive eyedrops for years with dry eye symptomatology.All patients received four sessions of IPL treatment using the Optima IPL system(Lumenis,Yokneam,Israel)adjusted to the official optimized Lumenis setting.Changes in symptomatology,corneal staining,conjunctival hyperemia,non-invasive break-up time(NIBUT),tear osmolarity,tear meniscus height(TMH),meiboscore and meibomian gland expressibility was analyzed after treatment.Results:Statistically significant reductions were observed after IPL treatment in the symptomatology scores measured with different questionnaires[ocular surface disease index(OSDI),standard patient evaluation of eye dryness(SPEED)and symptom assessment questionnaire in dry eye(sanDE)]as well as with the visual analogue scale(Pclusions:IPL therapy combined with meibomian gland expression(MGX)seems to be an effective option to improve symptomatology in glaucomatous patients with ocular surface disease due to prolonged hypotensive eyedrop treatment

关键词： Glaucoma Intense pulsed light Dry eye Meibomian glands

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Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第19期30卷 2512-2522页

作者： Juan Jose Urquijo-Ponce carlos Alventosa-Mateu Mercedes Latorre-Sánchez Inmaculada Castelló-Miralles Moisés Diago Hepatology Unit Department of Digestive Diseases Consorcio Hospital General Universitario of ValenciaValencia 46014Spain

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

关键词： Hepatocellular carcinoma Early stage Intermediate stage Neoadjuvant Adjuvant Systemic therapy

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From liver to hormones:The endocrine consequences of cirrhosis

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World Journal of Gastroenterology 2024年第9期30卷 1073-1095页

作者： Juan Eduardo Quiroz-Aldave Elman Rolando Gamarra-Osorio María del Carmen Durand-Vásquez Luciana del Pilar Rafael-Robles Jhean Gabriel Gonzáles-Yovera María Alejandra Quispe-Flores Luis Alberto Concepción-Urteaga Alejandro Román-González José Paz-Ibarra Marcio José Concepción-Zavaleta Non-communicable Diseases Endocrinology Research LineHospital de Apoyo ChepénChepén 13871Peru Department of Endocrinology Hospital Víctor Lazarte EchegarayTrujillo 13006Peru Department of Endocrinology Clínica Javier PradoLima 15046Peru Department of Gastroenterology Hospital Nacional Guillermo Almenara IrigoyénLima 15018Peru Department of Endocrinology Hospital de Emergencias GrauLima 15001Peru Internal Medicine Hospital Regional Docente de TrujilloTrujillo 13011Peru Department of Endocrinology Hospital Universitario de San Vicente FundaciónMedellin 050010Colombia Internal Medicine Universidad de AntioquiaMedellín 050010Colombia School of Medicine Universidad Nacional Mayor de San MarcosLima 15081Peru Department of Endocrinology Hospital Nacional Edgardo Rebagliati MartinsLima 15072Peru Carrera de Medicina Humana Universidad Científica del SurLima 15067Peru

Hepatocrinology explores the intricate relationship between liver function and the endocrine system.Chronic liver diseases such as liver cirrhosis can cause endocrine disorders due to toxin accumulation and protein synthesis disruption.Despite its importance,assessing endocrine issues in cirrhotic patients is frequently neglected.This article provides a comprehensive review of the epidemiology,pathophysiology,diagnosis,and treatment of endocrine disturbances in liver cirrhosis.The review was conducted using the PubMed/Medline,EMBASE,and Scielo databases,encompassing 172 articles.Liver cirrhosis is associated with endocrine disturbances,including diabetes,hypoglycemia,sarcopenia,thyroid dysfunction,hypogonadotropic hypogonadism,bone disease,adrenal insufficiency,growth hormone dysfunction,and secondary hyperaldosteronism.The optimal tools for diagnosing diabetes and detecting hypoglycemia are the oral glucose tolerance test and continuous glucose monitoring system,respectively.Sarcopenia can be assessed through imaging and functional tests,while other endocrine disorders are evaluated using hormonal assays and imaging studies.Treatment options include metformin,glucagon-like peptide-1 analogs,sodium-glucose co-transporter-2 inhibitors,and insulin,which are effective and safe for diabetes control.Established standards are followed for managing hypoglycemia,and hormone replacement therapy is often necessary for other endocrine dysfunctions.Liver transplantation can address some of these problems.

关键词： Diabetes mellitus Hypoglycemia Thyroid diseases Hypogonadism Metabolic bone diseases Liver cirrhosis

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Unveiling DNA methylation in Alzheimer’s disease:a review of array-based human brain studies

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Neural Regeneration Research 2024年第11期19卷 2365-2376页

作者： Victoria Cunha Alves Eva Carro Joana Figueiro-Silva Neurodegenerative Diseases Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Network Center for Biomedical Research Neurodegenerative Diseases(CIBERNED)MadridSpain PhD Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurotraumatology and Subarachnoid Hemorrhage Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Neurobiology of Alzheimer’s Disease Unit Functional Unit for Research Into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpain Institute of Medical Genetics University of ZurichZurichSwitzerland Department of Molecular Life Science University of ZurichZurichSwitzerland

The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.

关键词： Alzheimer’s disease ANK1 BIN1 DNA methylation epigenome-wide association studies HOXA3 MCF2L RHBDF2

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Dietary(poly)phenol intake is associated with cardiometabolic health parameters in adolescents

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Food Science and Human Wellness 2024年

作者： Emily P.Laveriano-santos Sara Castro-Barquero Camila Arancibia-Riveros Ana María Ruiz-León Rosa Casas Ramón Estruch Patricia Bodega Mercedes de Miguel Amaya de Cos-Gandoy Jesús Martínez-Gómez Gloria santos-Beneit Juan M.Fernández-Alvira Rodrigo Fernández-Jiménez Rosa M.Lamuela-Raventós Anna Tresserra-Rimbau The Zena and Michael A.Wiener Cardiovascular Institute Icahn School of Medicine at Mount Sinai Department de Nutrició Ciències de l'Alimentació I Gastronomia XIA Facultat de Farmàcia i Ciències de l'alimentació Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB) Universitat de Barcelona Department of Internal Medicine hospital clínic Institutd'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) University of Barcelona Consorcio CIBER M.P.Fisiopatología de la Obesidad y Nutrición (CIBERObn) Instituto de Salud carlos III (ISCIII) Mediterranean Diet Foundation 5. Foundation for Science Health and Education (SHE) 6. Centro Nacional de Investigaciones Cardiovasculares (CNIC) CIBER de Enfermedades Cardiovasculares (CIBERCV) 9. hospital universitario clínico san carlos

Background: The protective role of (poly)phenols against metabolic disorders has been extensively studied in adults but not in adolescents.Objective: To assess associations of dietary (poly)phenols and their subclasses with cardiometabolic health parameters in adolescents. Methods: A cross-sectional study was conducted in 944 individuals aged 11 to 14 years enrolled in the SI! Program for Secondary Schools trial (NCT03504059). (Poly)phenol intake was assessed using semi-quantitative food frequency questionnaires and the Phenol-Explorer database. The measured cardiometabolic parameters were waist circumference (WC) age-sex z-score， blood pressure (BP) age-sex z-score， blood glucose (BG)， triglycerides (TG)， and high-density lipoprotein cholesterol (HDL-c). Multilevel mixed-effect linear regression models were applied to examine the association between (poly)phenol quintiles and cardiometabolic health parameters.Results: Compared to the lowest quintile， adolescents in the highest quintile of total (poly)phenol intake had lower WC z-scores (β=-0.09， 95%CI=-0.09;-0.08， P-for trend=0.002)， mean arterial pressure z-scores (β =-0.11， 95%CI=-0.12;-0.09， P-for trend=0.206)， and HDL-c (β=-1.52， 95%CI=-2.90;-0.14， P-for trend=0.108)， after multivariable adjustment. The WC z-scores (β=-0.11， 95%CI=-0.19;-0.03， P-for trend=0.013) and HDL-c (β=-2.16， 95%CI=-3.78;-0.53， P-for trend=0.046) were lower in the highest quintile of flavonoid intake compared to the lowest quintile. The highest quintile of phenolic acid intake was associated with a lower WC z-score (β=-0.14， 95%CI=-0.26;-0.02， P-for trend=0.011) and TG levels (β=-8.83， 95%CI=-12.37;-5.30， P-for trend clusion: A higher intake of (poly)phenols， especially flavonoids， phenolic acids， and stilbenes

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Circadian rhythm disruption and retinal dysfunction:a bidirectional link in Alzheimer’s disease?

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Neural Regeneration Research 2024年第9期19卷 1967-1972页

作者： Laura Carrero DesireéAntequera Cristina Municio Eva Carro Group of Neurodegenerative Diseases Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpainNetwork Center for Biomedical Research in Neurodegenerative Diseases(CIBERNED)ISCIIIMadridSpain PhD Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurobiology of Alzheimer’s Disease Unit Functional Unit for Research into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpainNetwork Centre for Biomedical Research in Neurodegenerative Diseases(CIBERNED)ISCIIIMadridSpain

Dysfunction in circadian rhythms is a common occurrence in patients with Alzheimer’s disease.A predominant function of the retina is circadian synchronization,carrying information to the brain through the retinohypothalamic tract,which projects to the suprachiasmatic nucleus.Notably,Alzheimer’s disease hallmarks,including amyloid-β,are present in the retinas of Alzheimer’s disease patients,followed/associated by structural and functional disturbances.However,the mechanistic link between circadian dysfunction and the pathological changes affecting the retina in Alzheimer’s disease is not fully understood,although some studies point to the possibility that retinal dysfunction could be considered an early pathological process that directly modulates the circadian rhythm.

关键词： Alzheimer’s disease amyloid circadian rhythm neurodegeneration retina

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The dorsal root ganglion as a target for neurorestoration in neuropathic pain

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Neural Regeneration Research 2024年第2期19卷 296-301页

作者： Guillermo Estivill-Torrús Ana Belen Martínez-Padilla Lourdes Sánchez-Salido Anne Baron-Van Evercooren Beatriz García-Díaz Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina(IBIMA Plataforma BIONAND) MálagaSpain Unidad clínica de Neurociencias Hospital Regional Universitario de MálagaMálagaSpain Departamento de Biología Molecular y Bioquímica Universidad de MálagaSpain Sorbonne Université Institut du Cerveau-Paris Brain Institute-ICMINSERMCNRSAP-HPHôpital Pitié-SalpêtrièreParisFrance

Neuropathic pain is a severe and chronic condition widely found in the general population.The reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in patients.During the processing of pain,the dorsal root ganglia constitute an important region where dorsal root ganglion neurons play a crucial role in the transmission and propagation of sensory electrical stimulation.Furthermore,the dorsal root ganglia have recently exhibited a regenerative capacity that should not be neglected in the understanding of the development and resolution of neuropathic pain and in the elucidation of innovative therapies.Here,we will review the complex interplay between cells(satellite glial cells and inflammatory cells)and factors(cytokines,neurotrophic factors and genetic factors)that takes place within the dorsal root ganglia and accounts for the generation of the aberrant excitation of primary sensory neurons occurring in neuropathic pain.More importantly,we will summarize an updated view of the current pharmacologic and nonpharmacologic therapies targeting the dorsal root ganglia for the treatment of neuropathic pain.

关键词： cytokines dorsal root ganglia genetic factors neuropathic pain neurotrophic factors pharmacologic and nonpharmacologic therapies satellite glial cells sensory neurons

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