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Hepatocardiorenal syndrome in liver cirrhosis:Recognition of a new entity?

World Journal of Gastroenterology 2024年第2期30卷 128-136页

作者： henry H l Wu Amina Rakisheva Arvind Ponnusamy Rajkumar Chinnadurai Renal Research Kolling Institute of Medical ResearchRoyal North Shore Hospital&The University of SydneySt.Leonards(Sydney)2065New South WalesAustralia Department of Cardiology City Cardiological CenterAlmaty 050000Kazakhstan Department of Renal Medicine Royal Preston HospitalPreston PR29HTUnited Kingdom Donal O’Donoghue Renal Research Centre&Department of Renal Medicine Northern Care Alliance National Health Service Foundation TrustSalford M68HDUnited Kingdom

Emerging evidence and perspectives have pointed towards the heart playing an important role in hepatorenal syndrome(HRS),outside of conventional understanding that liver cirrhosis is traditionally considered the sole origin of a cascade of pathophysiological mechanisms directly affecting the kidneys in this context.In the absence of established heart disease,cirrhotic cardiomyopathy may occur more frequently in those with liver cirrhosis and kidney disease.It is a specific form of cardiac dysfunction characterized by blunted contractile responsiveness to stress stimuli and altered diastolic relaxation with electrophysiological abnormalities.Despite the clinical description of these potential cardiac-related complications of the liver,the role of the heart has traditionally been an overlooked aspect of circulatory dysfunction in HRS.Yet from a physiological sense,temporality(prior onset)of cardiorenal interactions in HRS and positive effects stemming from portosystemic shunting demonstrated an important role of the heart in the development and progression of kidney dysfunction in cirrhotic patients.In this review,we discuss current concepts surrounding how the heart may influence the development and progression of HRS,and the role of systemic inflammation and endothelial dysfunction causing circulatory dysfunction within this setting.The temporality of heart and kidney dysfunction in HRS will be discussed.For a subgroup of patients who receive portosystemic shunting,the dynamics of cardiorenal interactions following treatment is reviewed.Continued research to determine the unknowns in this topic is anticipated,hopefully to further clarify the intricacies surrounding the liver-heart-kidney connection and improve strategies for management.

关键词： Hepatorenal syndrome Cardiorenal syndrome Cirrhosis Cardiac dysfunction Circulatory dysfunction

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Immunotherapy in triple-negative breast cancer:A literature review and new advances

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World Journal of Clinical Oncology 2022年第3期13卷 219-236页

作者： Guillermo Arturo Valencia Patricia Rioja Zaida Morante Rossana Ruiz Hugo Fuentes Carlos A Castaneda Tatiana Vidaurre Silvia Neciosup henry l gomez Department of Medical Oncology Instituto Nacional de Enfermedades NeoplásicasLima 15036Peru

Triple-negative breast cancer(TNBC)is a highly complex,heterogeneous disease and historically has limited treatment options.It has a high probability of disease recurrence and rapid disease progression despite adequate systemic treatment.Immunotherapy has emerged as an important alternative in the management of this malignancy,showing an impact on progression-free survival and overall survival in selected populations.In this review we focused on immunotherapy and its current relevance in the management of TNBC,including various scenarios(metastatic and early-neoadjuvant,adjuvant-),new advances in this subtype and the research of potential predictive biomarkers of response to treatment.

关键词： Triple-negative breast cancer Early disease Immunotherapy Biomarkers Metastatic disease

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Protective effects of cyclosporine and its analog NIM-811 in a murine model of hepatic ischemia-reperfusion injury

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liver Research 2024年第1期8卷 46-53页

作者： Joshua Hefler Rena Pawlick Braulio A.Marfil-Garza Aducio Thiesen Nerea Cuesta-gomez Sanaz Hatami Darren H.Freed Constantine Karvellas David l.Bigam A.M.James Shapiro Department of Surgery Faculty of Medicine&DentistryUniversity of AlbertaEdmontonABCanada Department of Medicine Faculty of Medicine&DentistryUniversity of AlbertaEdmontonABCanada CHRISTUS-latAm Hub Excellence&Innovation Center MonterreyMexico Alberta Diabetes Institute University of AlbertaEdmontonABCanada Clinical Islet Transplant Program University of AlbertaEdmontonABCanada Department of laboratory Medicine&Pathology Faculty of Medicine&DentistryUniversity of AlbertaEdmontonABCanada

Background and aim:The liver is susceptible to ischemia-reperfusion injury(IRI)during hepatic surgery,when the vessels are compressed to control bleeding,or liver transplantation,when there is an obligate period of ischemia.The hallmark of IRI comprises mitochondrial dysfunction,which generates reactive oxygen species,and cell death through necrosis or apoptosis.Cyclosporine(CsA),which is a well-known immunosuppressive agent that inhibits calcineurin,has the additional effect of inhibiting the mito-chondrial permeability transition pore(mPTP),thereby,preventing mitochondrial swelling and injury.NIM-811,which is the nonimmunosuppressive analog of CsA,has a similar effect on the mPTP.In this study,we tested the effect of both agents on mitigating warm hepatic IRI in a murine model.Materials and methods:Before ischemic insult,the mice were administered with intraperitoneal normal saline(control);CsA at 2.5,10,or 25 mg/kg;or NIM-811 at 10 mg/kg.Thereafter,the mice were subjected to partial warm hepatic ischemia by selective pedicle clamping for 60 min,followed by 6 h of recovery after reperfusion.Serum alanine transaminase(AlT)was measured,and the liver tissue was examined histologically for the presence of apoptosis and the levels of inflammatory cytokines.Results:Compared with the control mice,the mice treated with 10 and 25 mg/kg of CsA and NIM-811 had significantly lower AlT levels(Ply).Moreover,the liver tissue showed reduced histological injury scores after treatment with CsA at 2.5,10,and 25 mg/kg and NIM-811(P=0.041,ly)and significant decrease in apoptosis after treatment with CsA at all doses(P=0.012,0.007,andly).levels of the pro-inflammatory cyto-kines,particularly interleukin(Il)-1β,Il-2,Il-4,Il-10,and keratinocyte chemoattractant/human growth-regulated oncogene significantly decreased in the mice treated with the highest dose of CsA(25 mg/kg)than those in the control mice.Conclusions:Premedication with CsA or NIM-811 mitig

关键词： Cyclosporine(CsA) Cyclosporine analogue liver surgery Ischemia-reperfusion injury(IRI) Animal model NIM-811

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Multi-tissue transcriptomics of a unique monozygotic discordant twin case of severe progressive osseous heteroplasia

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Genes & Diseases 2024年第3期11卷 22-25页

作者： Alberto gomez-Carballa Maria Jose Curras-Tuala Sara Pischedda Miriam Cebey-lopez Jose gomez-Rial Irene Rivero-Cale Jacobo Pardo-seco Xabier Bello Sandra Viz-lasheras Antonio Justicia-Grande Julian Montoto-louzao Alba Camino-Mera Isabel Ferreiros-Vidal Maximo Fraga Jose RAntunez Rodolfo gomez Federico Martinon-Torres Antonio Salas Genetics Vaccines and Infections Research Group(GENVIP)Instituto de Investigacion Sanitaria de SantiagoSantiagode CompostelaGalicia 15706Spain Translational Pediatrics and Infectious Diseases Department of PediatricsHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain laboratorio de Inmunologia Servicio de Andlisis ClinicosHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain Unidade de Xenetica Instituto de Ciencias Forenses(INCIFOR)Facultade de MedicinaUniversidade de Santiago de Compostelaand GenPoB Research GroupInstituto de Investigacion SanitariaHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain Musculoskeletal Pathology Group Instituto de Investigacion Sanitaria de SantiagoServicio Galego de Saude(SERGAS)Santiago de CompostelaGalicia 15706Spain Department of Pathology Hospital Clinico Universitario de Santiago de Compostela(SERGAS)Galicia 15706Spain Unidad Integrada de BiobancosBiomodelos 3D y Modelos Animales IDIS(lnstituto de Investigacion Sanitaria de Santiagode Compostela)Galicia15706Spain Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias(CIBER-ES) MadridSpain

Progressive osseous heteroplasia(POH)is an ultra-rare autosomal dominant disabling disorder characterized by heterotopic ossification(HO).It is caused by heterozygous inactivating mutations in the GNAS(guanine nucleotide-binding protein alpha-stimulating activity polypeptide)gene.However,the molecular mechanisms underlying HO remain poorly understood.As a treatment for POH is not yet available,the identification of the mechanisms driving POH in affected tissues using gene expression may be of great help to underestand the molecular basis of POH and develop new therapeutic approaches.

关键词： stimulating driving asi

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Plant cell wall-mediated disease resistance:Current understanding and future perspectives

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Molecular Plant 2024年第5期17卷 699-724页

作者： Antonio Molina lucıa Jorda Miguel Angel Torres Marina Martın-Dacal Diego Jose Berlanga Patricia Fernandez-Calvo Elena gomez-Rubio Sonsoles Martın-Santamarıa Centro de Biotecnología y Genómica de Plantas Universidad Politécnica de Madrid(UPM)-Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria(INIA/CSIC)Campus de Montegancedo UPMPozuelo de Alarcon(Madrid)Spain Departamento de Biotecnologıa-Biología Vegetal Escuela Técnica Superior de Ingenierıa AgronomicaAlimentarıa y de BiosistemasUPMMadridSpain Centro de Investigaciones Biologicas Margarita Salas Consejo Superior de Investigaciones Científicas(CSIC)Ramiro de Maeztu 928040 MadridSpain Misión Biológica de Galicia Consejo Superior de Investigaciones Científicas(CSIC)Campus de Montegancedo UPMPozuelo de Alarcón(Madrid)Spain

Beyond their function as structural barriers,plant cell walls are essential elements for the adaptation of plants to environmental conditions.Cell walls are dynamic structures whose composition and integrity can be altered in response to environmental challenges and developmental cues.These wall changes are perceived by plant sensors/receptors to trigger adaptative responses during development and upon stress perception.Plant cell wall damage caused by pathogen infection,wounding,or other stresses leads to the release of wall molecules,such as carbohydrates(glycans),that function as damage-associated molecular patterns(DAMPs).DAMPs are perceived by the extracellular ectodomains(ECDs)of pattern recognition receptors(PRRs)to activate pattern-triggered immunity(PTI)and disease resistance.Similarly,glycans released from the walls and extracellular layers of microorganisms interacting with plants are recognized as microbe-associated molecular patterns(MAMPs)by specific ECD-PRRs triggering PTI responses.The number of oligosaccharides DAMPs/MAMPs identified that are perceived by plants has increased in recent years.However,the structural mechanisms underlying glycan recognition by plant PRRs remain limited.Currently,this knowledge is mainly focused on receptors of the lysM-PRR family,which are involved in the perception of various molecules,such as chitooligosaccharides from fungi and lipo-chitooligosaccharides(i.e.,Nod/MYC factors from bacteria and mycorrhiza,respectively)that trigger differential physiological responses.Nevertheless,additional families of plant PRRs have recently been implicated in oligosaccharide/polysaccharide recognition.These include receptor kinases(RKs)with leucine-rich repeat and Malectin domains in their ECDs(lRR-MAl RKs),Catharanthus roseus RECEPTOR-lIKE KINASE 1-lIKE group(CrRlK1l)with Malectin-like domains in their ECDs,as well as wall-associated kinases,lectin-RKs,and lRR-extensins.The characterization of structural basis of glycans recognition by these new plant receptors will shed light

关键词： Arabidopsis thaliana cell wall damage-associated molecular patterns DAMPs disease resistance glycans oligosaccharides pattern-triggered immunity PTl pattern recognition receptor PRRs

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Unveiling strain-enhanced moiréexciton localization in twisted van der Waals homostructures

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Nano Research 2024年第4期17卷 3245-3252页

作者： henry Rui He Haihong Zheng Biao Wu Shaofei li Junnan Ding Zongwen liu Jian-Tao Wang Anlian Pan Yanping liu Institute of Quantum Physics School of PhysicsCentral South UniversityChangsha 410083China State Key laboratory of Precision Manufacturing for Extreme Service Performance Central South UniversityChangsha 410083China School of Chemical and Biomolecular Engineering The University of SydneyNSW 2006Australia Beijing National laboratory for Condensed Matter Physics Institute of PhysicsChinese Academy of SciencesBeijing 100190China College of Materials Science and Engineering Hunan UniversityChangsha 410082China State Key laboratory of High-Performance Complex Manufacturing Central South UniversityChangsha 410083China Shenzhen Research Institute of Central South University Shenzhen 51800China

Moirésuperlattices,arising from the controlled twisting of van der Waals homostructures at specific angles,have emerged as a promising platform for quantum emission applications.Concurrently,the manipulation of strain provides a versatile strategy to finely adjust electronic band structures,enhance exciton luminescence efficiency,and establish a robust foundation for two-dimensional quantum light sources.However,the intricate interplay between strain and moirépotential remains partially unexplored.Here,we introduce a meticulously designed fusion of strain engineering and the twisted 2l-WSe_(2)/2l-WSe_(2) homobilayers,resulting in the precise localization of moiréexcitons.Employing low-temperature photoluminescence spectroscopy,we unveil the emergence of highly localized moiré-enhanced emission,characterized by the presence of multiple distinct emission lines.Furthermore,our investigation demonstrates the effective regulation of moirépotential depths through strain engineering,with the potential depths of strained and unstrained regions differing by 91%.By combining both experimental and theoretical approaches,our study elucidates the complex relationship between strain and moirépotential,thereby opening avenues for generating strain-induced moiréexciton single-photon sources.

关键词： moirésuperlattices strain engineering moiréexcitons moirépotential

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Clinicopathological predictors of long-term benefit in breast cancer treated with neoadjuvant chemotherapy

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World Journal of Clinical Oncology 2018年第2期9卷 33-41页

作者： Marco Galvez Carlos A Castaneda Joselyn Sanchez Miluska Castillo lia Pamela Rebaza Gabriela Calderon Miguel De la Cruz Jose Manuel Cotrina Julio Abugattas Jorge Dunstan henry Guerra Omar Mejia henry l gomez Department of Medical Oncology Instituto Nacional de Enfermedades Neoplasicas Faculty of Medicine Universidad Peruana San Juan Bautista Department of Research Instituto Nacional de Enfermedades Neoplasicas Department of Breast Cancer Surgery Instituto Nacional de Enfermedades Neoplasicas Department of Pathology Instituto Nacional de Enfermedades Neoplasicas

AIM To investigate the survival impact of clinicopathological factors, including pathological complete response(p CR) and tumor-infiltrating lymphocytes(s TIl) levels according to subtypes, in breast cancer(BC) patients who received neo-adjuvant chemotherapy(NAC).METHODS We evaluated 435 BC patients who presented and received NAC at the Instituto Nacional de Enfermedades Neoplasicas from 2003 to 2014. s TIl was analyzed as the proportion of tumor stroma occupied by lymphocytes, and was prospectively evaluated on hematoxylin and eosin-stained sections of the preN AC core biopsy. p CR was considered in the absence of infiltrating cancer cells in primary tumor and axillary lymph nodes. Analysis of statistical association between clinical pathological features, s TIl, p CR and survival were carried out using SPSSvs19.RESUlTS Median age was 49 years(range 24-84 years) and the most frequent clinical stage was ⅢB(58.3%). luminal A, luminal B, HER2-enriched and(triple-negative) TN phenotype was found in 24.6%, 37.9%, 17.7% and 19.8%, respectively. p CR was observed in 11% and median percentage of s TIl was 40%(2%-95%) in the whole population. p CR was associated to Ct1-2(P = 0.045) and to high s TIl(P = 0.029) in the whole population. There was a slight trend towards significance for s TIl(P = 0.054) in luminal A. s TIl was associated with grade Ⅲ(P luminal A subtype(P le population. longer disease-free survival was associated with grade Ⅰ-Ⅱ(P = 0.006), cN 0(P linical stage Ⅱ(P = 0.004), ER-positive(P luminal A(P longer disease-free survival was associated with grade Ⅰ-Ⅱ in luminal A(P luminal A(P = 0.045) and TNBC(P = 0.01), clinical stage Ⅱ in luminal A(P = 0.003) and TNBC(P = 0.038), and pC R in TNBC(P longer overall survival was associated with grade Ⅰ-Ⅱ(P < 0.001), ER-positive(P < 0.001),

关键词： Breast cancer Subtype Tumor-infiltrating lymphocytes Neoadjuvant therapy Pathological complete response Survival

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PIK3CA mutation in non-metastatic triple-negative breast cancer as a potential biomarker of early relapse:A case report

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World Journal of Clinical Oncology 2021年第8期12卷 702-711页

作者： Guillermo Arturo Valencia Patricia Rioja Zaida Morante Jhajaira M Araujo Heberth Daniel Vallejos henry Guerra henry l gomez Department of Medical Oncology Instituto Nacional de Enfermedades NeoplásicasLima 15000Peru Escuela de Medicina Humana Universidad Privada San Juan BautistaLima 15067Peru Department of Medical Oncology Russian Scientific Center of Radiology and RadiotherapyKonkovo 117485MoscowRussia Department of Pathology Instituto Nacional de Enfermedades NeoplásicasLima 15000Peru

BACKGROUND Currently,the detection of PIK3CA mutations is of special interest in personalized medicine because it is frequently found in triple-negative breast cancer(TNBC).The PI3KCA mutation is an independent negative prognostic factor for survival in metastatic breast cancer,and its prognostic value in liquid biopsy as a biomarker of treatment and early relapse is under investigation,both for metastatic disease and neoadjuvant scenario with curative intent.CASE SUMMARY A 54-year-old female patient with TNBC clinical stage IIIA,who,after receiving neoadjuvant chemotherapy(based on anthracyclines and taxanes),surgery,radiotherapy,and adjuvant capecitabine,was detected with a PI3KCA mutation in tissue and peripheral blood(ctDNA in liquid biopsy).After 10 mo,the patient had disease relapse of left cervical node disease.CONClUSION The detection of PIK3CA mutation in TNBC after neoadjuvant treatment might be associated with early relapse or rapid disease progression.

关键词： Triple-negative breast cancer PIK3CA mutation liquid biopsy Early relapse Biomarker Case report

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A comprehensive look at the psychoneuroimmunoendocrinology of spinal cord injury and its progression: mechanisms and clinical opportunities

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Military Medical Research 2024年第2期11卷 228-267页

作者： Miguel A.Ortega Oscar Fraile-Martinez Cielo García-Montero Sergio Haro Miguel Ángel Álvarez-Mon Diego De leon-Oliva Ana M.gomez-lahoz Jorge Monserrat Mar Atienza-Pérez David Díaz Elisa lopez-Dolado Melchor Álvarez-Mon Department of Medicine and Medical Specialities University of Alcala28801 Alcala de HenaresSpain Ramón y Cajal Institute of Sanitary Research(IRYCIS) 28034 MadridSpain Department of Psychiatry and Mental Health Hospital Universitario Infanta Leonor28031 MadridSpain Service of Rehabilitation National Hospital for Paraplegic PatientsCarr.de la PeraledaS/N45004 ToledoSpain Immune System Diseases‑Rheumatology Service and Internal Medicine University Hospital Príncipe de Asturias(CIBEREHD)28806 Alcala de HenaresSpain

Spinal cord injury(SCI)is a devastating and disabling medical condition generally caused by a traumatic event(primary injury).This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate neural damage but also exacerbate initial damage(secondary injury).The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after SCI,explaining the progression and detrimental consequences related to this condition.Psychoneuroimmunoendocrinology(PNIE)is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism,considering the mind and the body as a whole.The initial traumatic event and the consequent neurological disruption trigger immune,endocrine,and multisystem dysfunction,which in turn affect the patient's psyche and well-being.In the present review,we will explore the most important local and systemic consequences of SCI from a PNIE perspective,defining the changes occurring in each system and how all these mechanisms are interconnected.Finally,potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical management of these patients.

关键词： Spinal cord injury(SCI) Psychoneuroimmunoendocrinology(PNIE) Secondary injury Immunoinflammatory dysfunction Gut microbiota Translational opportunities

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Existence of Solutions of a Convolution Integral Equation

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Journal of Applied Mathematics and Physics 2024年第5期12卷 1835-1847页

作者： henry Otoo Benjamin Dadzie Mensah lewis Brew Mathematical Sciences Department University of Mines and Technology Tarkwa Ghana Faculty of Science and Technology University of Silesia in Katowice Sosnowiec Poland

In this study, we prove the of existence of solutions of a convolution Volterra integral equation in the space of the lebesgue integrable function on the set of positive real numbers and with the standard norm defined on it. An operator P was assigned to the convolution integral operator which was later expressed in terms of the superposition operator and the nonlinear operator. Given a ball Br belonging to the space l it was established that the operator P maps the ball into itself. The Hausdorff measure of noncompactness was then applied by first proving that given a set M∈ B r the set is bounded, closed, convex and nondecreasing. Finally, the Darbo fixed point theorem was applied on the measure obtained from the set E belonging to M. From this application, it was observed that the conditions for the Darbo fixed point theorem was satisfied. This indicated the presence of at least a fixed point for the integral equation which thereby implying the existence of solutions for the integral equation.

关键词： Volterra Integral Equation Convolution Fixed Point Existence Noncompactness

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