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Association between Helicobacter pylori infection,mismatch repair,HER2 and tumor-infiltrating lymphocytes in gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2487-2503页

作者： Carlos A Castaneda Miluska Castillo Luis A Bernabe Joselyn Sanchez Matteo Fassan Katherine Tello Ignacio Ivan Wistuba Ivan Chavez Passiuri Eloy Ruiz Juvenal Sanchez Fernando Barreda Daniel valdivia Yaqueline Bazan Milagros Abad-Licham Claudio Mengoa Hugo Fuentes Paola Montenegro Ebert Poquioma Raul Alatrista Claudio J Flores Luis Taxa Faculty of Health Sciences Universidad Cientifica del SurLima 15038Peru GECO PERU Grupo de Estudios Clinicos Oncologicos del PeruLima 15038Peru Department of Research Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Faculty of Human Medicine Universidad Ricardo PalmaLima 15039Peru Department of Medicine Surgical Pathology&Cytopathology UnitUniversity of PaduaPadua 35121Italy Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer CenterHoustonTX 77030United States Department of Abdominal Surgery Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Medical Specialties Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Regional de Enfermedades Neoplasicas del NorteTrujillo 13001Peru Faculty of Human Medicine Universidad Privada Antenor OrregoTrujillo 13008Peru Department of Surgery Instituto Regional de Enfermedades Neoplasicas del SurArequipa 04002Peru Department of Medical Oncology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Epidemiology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Unidad de Investigación Básica y Traslacional Oncosalud-AUNALima 15038Peru Faculty of Medicine Universidad San Martin de PorresLima 15008Peru

BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.AIM To determine the rates of deficient mismatch-repair(dMMR),HER2-status and H.pylori infection and their association with TIL levels in GC.METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)compartments.The density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).H.pylori infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of samples.RESULTS dMMR was found in 34.4%,HER2+in 5%and H.pylori-positive in 55.7%of samples.High IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)densities.HER2-was associated with high IT-CD8(P=0.009).H.pylorinegative was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and H.pylori-negativity.Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.

关键词： Lymphocytes Macrophages Gastric cancer Helicobacter pylori HER2 Mismatch repair

Local renin angiotensin system and sperm DNA fragmentation

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Asian Journal of Andrology 2022年第2期24卷 139-146页

作者： María Victoria Aparicio Prieto María Victoria Rodríguez Gallego Asier valdivia Palacín Yosu Franco Iriarte Gotzone Hervás Barbara Enrique Echevarría Orella Luis Casis Saenz Human Reproduction Unit Cruces University HospitalBarakaldo 48903Spain Human Reproduction Unit San Pedro HospitalLogroño 26006Spain Department of Physiology Faculty of Medicine and NursingUniversity of the Basque Country(UPV/EHU)Leioa 48940Spain Human Reproduction Unit Ruber International HospitalMadrid 28034Spain

The renin angiotensin system(RAS)appears to influence male fertility at multiple levels.In this work,we analyzed the relationship between the RAS and DNA integrity.Fifty male volunteers were divided into two groups(25 each):control(DNA fragmentation≤20%)and pathological(DNA fragmentation>20%)cases.Activities of five peptidases controlling RAS were measured fluorometrically:prolyl endopeptidase(which converts angiotensin[A]I and A II to A 1–7),neutral endopeptidase(NEP/CD10:A I to A 1–7),aminopeptidase N(APN/CD13:A III to A IV),aminopeptidase A(A II to A III)and aminopeptidase B(A III to A IV).Angiotensin-converting enzyme(A I to A II),APN/CD13 and NEP/CD10 were also assessed by semiquantitative cytometry and quantitative flow cytometry assays,as were the receptors of all RAS components:A II receptor type 1(AT1R),A II receptor type 2(AT2R),A IV receptor(AT4R or insulin-regulated aminopeptidase[IRAP]),(pro)renin receptor(PRR)and A 1–7 receptor or Mas receptor(MasR)None of the enzymes that regulate levels of RAS components,except for APN/CD13(decrease in fragmented cells),showed significant differences between both groups.Micrographs of RAS receptors revealed no significant differences in immunolabeling patterns between normozoospermic and fragmented cells.Labeling of AT1R(94.3%normozoospermic vs 84.1%fragmented),AT4R(96.2%vs 95.3%)and MasR(97.4%vs 87.2%)was similar between the groups.AT2R(87.4%normozoospermic vs 63.1%fragmented)and PRR(96.4%vs 48.2%)were higher in non-fragmented spermatozoa.These findings suggest that fragmented DNA spermatozoa have a lower capacity to respond to bioactive RAS peptides.

关键词： DNA fragmentation local renin angiotensin system sperm fertility

Isla San Pedro Nolasco as a Late Miocene intrusive record at the eastern margin of the Gulf of California:Insights from geological,geochemical and geochronological studies

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Geoscience Frontiers 2022年第3期13卷 100-114页

作者： L.A.Velderrain-Rojas J.R.Vidal-Solano L.M.Alva-valdivia R.Vega-Granillo M.López-Martinez Departamento de Geología División de Ciencias Exactas y NaturalesUniversidad de SonoraC.P.83000 HermosilloSonoraMexico Laboratorio de Paleomagnetismo Instituto de GeofísicaUniversidad Nacional Autónoma de MéxicoCircuito de la Investigación CientíficaC.P.04510 MéxicoD.F.Mexico Departamento de Geología División de Ciencias de la TierraCentro de Investigación Científica y de Educación Superior de EnsenadaBaja CaliforniaMexico

Isla San Pedro Nolasco(ISPN)is a structural high bounded by inactive dextral oblique-slip faults in the east-central part of the Gulf of California rift zone and is composed of intrusive rocks not exposed on other Gulf of California islands.Here we present the reconnaissance results from geological mapping,as well as first geochemical and geochronological data for the ISPN intrusive complex.The intrusive rocks compose a sheet-like body of intermediate and felsic composition intruded by an intermediate and acidic dike swarm.All intrusive rocks(host and dikes)range in age from ca.9 Ma to 10 Ma(^(40)Ar/^(39)Ar)and show a hydrous ferromagnesian mineral association(amphibole and biotite)with a calc-alkalic and transitional affinity.This hydrated mineralogical association has not been recognized in the coeval rocks along the onshore western margin of the North American plate(coastal Sonora).However,such hydrous mineralogical association is found in the coeval rift transitional volcanic rocks from the Baja California Microplate at Santa Rosalía and Bahía de LosÁngeles–Bahía de LasÁnimas.The ISPN continental block,at least 40 km long,has been pulled apart by transtensional faulting of the late Miocene Gulf of California shear zone before the westward migration of the North America-Pacific plate boundary at ca.3–2 Ma.Eventually,ISPN became isolated as an island during the late Miocene flooding of the Gulf of California seaway.

关键词： PAC-NAM plate boundary Gulf of California Intrusive rocks Isla San Pedro Nolasco

Arrhythmogenic mechanisms in ryanodine receptor channelopathies

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Science China(Life Sciences) 2015年第1期58卷 54-58页

作者： ZHAO Yan-Ting valdivia Carmen R. GURROLA Georgina B. HERNNDEZ Jonathan J. valdivia Héctor H. Center for Arrhythmia Research Department of Internal MedicineCardiovascular DivisionUniversity of Michigan

Ryanodine receptors(Ry Rs) are the calcium release channels of sarcoplasmic reticulum(SR) that provide the majority of calcium ions(Ca2+) necessary to induce contraction of cardiac and skeletal muscle cells.In their intracellular environment,Ry R channels are regulated by a variety of cytosolic and luminal factors so that their output signal(Ca2+) induces finely-graded cell contraction without igniting cellular processes that may lead to aberrant electrical activity(ventricular arrhythmias) or cellular remodeling.The importance of Ry R dysfunction has been recently highlighted with the demonstration that point mutations in RYR2,the gene encoding for the cardiac isoform of the Ry R(Ry R2),are associated with catecholaminergic polymorphic ventricular tachycardia(CPVT),an arrhythmogenic syndrome characterized by the development of adrenergically-mediated ventricular tachycardia in individuals with an apparently normal heart.Here we summarize the state of the field in regards to the main arrhythmogenic mechanisms triggered by Ry R2 channels harboring mutations linked to CPVT.Most CPVT mutations characterized to date endow Ry R2 channels with a gain of function,resulting in hyperactive channels that release Ca2+ spontaneously,especially during diastole.The spontaneous Ca2+ release is extruded by the electrogenic Na+/Ca2+ exchanger,which depolarizes the external membrane(delayed afterdepolarization or DAD) and may trigger untimely action potentials.However,a rare set of CPVT mutations yield Ry R2 channels that are intrinsically hypo-active and hypo-responsive to stimuli,and it is unclear whether these channels release Ca2+ spontaneously during diastole.We discuss novel cellular mechanisms that appear more suitable to explain ventricular arrhythmias due to Ry R2 loss-of-function mutations.

关键词：心律失常细胞机制离子通道受体骨骼肌细胞碱细胞收缩钙释放通道

Detection of Antinuclear Antibodies in Canine Serum by Immunoperoxidase in MDCK and Indirect Immunofluorescence in HEp2 Cells

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Open Journal of Veterinary Medicine 2023年第5期13卷 41-52页

作者： Guillermo valdivia Anda Edgar Guillermo valdivia Lara Ana Cristina Calderón Uribe Alejandra Andrea Escobar Patiño Gloria Elena Lara Reyes Laboratorio de Patogenicidad Microbiana Unidad de Investigación Multidisciplinaria FESC UNAM México City México Departamento de Patología Universidad Complutense de Madrid Madrid Espa&#241a Laboratorio DIVeT^® </sup> Estado de México México City México

Antinuclear antibodies are found in animals suffering from Systemic Lupus Erythematosus (SLE) and some other diseases, their presence in the blood is determined by antinuclear antibody (ANA) test using indirect immunofluorescence (IF) with HEp2 cells as a substrate. In this work, an immunoperoxidase (IP) assay was developed to evaluate the ANAs in canine sera, using canine kidney cell lines (MDCK) and compared with a commercial immunofluorescence test on Hep2 cells for this system, a fluoresceinated anti-canine Ig antibody was standardized. The study was performed on 50 sera from dogs submitted to the laboratory with different clinical diagnoses of autoimmune-associated diseases. The procedures on both cells were unified to perform comparisons of the reactions, direct sera or at different dilutions were added to a monolayer of permeabilized MDCK cells, followed by a peroxidized anti-canine IgG conjugate, and a substrate for the IP reaction. The same sera were tested on the commercial IF assay on Hep2 cell system. In 22/50 cases, the presence of LE cells in peripheral blood was determined. A high correlation was found in the detection of antinuclear antibodies between both cell lines and techniques, however there were differences in the reaction patterns in the nucleus and cytoplasm between cell lines. The diffuse nuclear pattern observed in MDCK cells was more related to the presence of high percentages of LE cells in peripheral blood. The differences found in the results were possibly associated with the presence of homologous antigens between the MDCK cells and the dog. In addition, the methodology and standardization for the use and interpretation of a reference serum was developed to unify the interpretation criteria in the laboratory.

关键词： Antinuclear Antibodies Immunoperoxidase in Marbin Darbin Canine Kidney (MDCK) SLE Associate Disease

Soft tissue swelling incidence using demineralized bone matrix in the outpatient setting

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世界骨科杂志：英文版 2017年第10期8卷 770-776页

作者： Kingsley R Chin Fabio JR Pencle Jason A Seale Juan M valdivia Charles E. Schmidt College of Medicine at Florida Atlantic University Less Ex-posure Surgery Specialists Institute Herbert Wertheim College of Medicine at Florida International University Less Exposure Surgery Society

AIM To assess use of demineralized bone matrix(DBM) use in anterior cervical discectomy and fusion(ACDF) in outpatient setting.METHODS One hundred and forty-five patients with prospectively collected data undergoing single and two level ACDF with DBM packed within and anterior to polyetheretherketone(PEEK) cages. Two groups created, Group 1(75) outpatients and control Group 2(70) hospital patients. Prevertebral soft tissue swelling(PVSTS) was measured anterior to C2 and C6 on plain lateral cervical radiographs preoperatively and one week postoperatively and fusion assessed at two years. RESULTS There was no intergroup significance between preoperative and postoperative visual analogue scales(VAS)and neck disability index(NDI) scores between Group 1 and 2. Mean preoperative PVSTS in Group 1 was 4.7 ± 0.2 mm at C2 level and 11.1 ± 0.5 at C6 level compared to Group 2 mean PVSTS of 4.5 ± 0.5 mm and 12.8 ± 0.5, P = 0.172 and 0.127 respectively. There was no radiographic or clinical evidence of adverse reaction noted. In Group 1 mean postoperative PVSTS was 5.5 ± 0.4 mm at C2 and 14.9 ± 0.6 mm at C6 compared Group 2 mean PVSTS was 4.9 ± 0.3 mm at C2 and 14.8 ± 0.5 mm at C6, P = 0.212 and 0.946 respectively. No significant increase in prevertebral soft tissue space at C2 and C6 level demonstrated.CONCLUSION ACDF with adjunct DBM packed PEEK cages showed a statistical significant intragroup improvement in VAS neck pain scores and NDI scores(P = 0.001). There were no reported serious patient complications; post-operative radiographs demonstrated no significant difference in prevertebral space. We conclude that ACDF with DBMpacked PEEK cages can be safely done in an ASC with satisfactory outcomes.

关键词： Ambulatory surgery center Anterior cervical discectomy and fusion Demineralized bone matrix Less Exposure Surgery Packed polyetheretherketone cages

SARS-CoV-2 spike RBD-specific IgA and IgG antibodies in breast milk after vaccination with the protein subunit vaccine Abdala

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Infectious Medicine 2022年第4期1卷 253-261页

作者： Maylin Pérez-Bernal Carlos Hernández Rafael Ibargollín Midalis Martínez Migdiala Soria Magali Delgado Onel valdivia DayamíDorta Andy Domínguez Enrique Pérez Yeosvany Cabreraa Research&Development Department Center for Genetic Engineering and BiotechnologyCircunvalante NorteOlivos IIISancti SpiritusCuba Neonatology Service General Hospital“Camilo Cienfuegos”128 Bartolome MasoSancti SpiritusCuba Production Department Center for Genetic Engineering and BiotechnologyCircunvalante NorteOlivos IIISancti SpiritusCuba

Background:COVID-19 vaccines that trigger a strong secretory antibody response in breast milk may achieve effective passive protection of vulnerable newborns and breastfed infants of immunized mothers.The aim of this work was to investigate the presence of SARS-CoV-2 spike RBD-specific IgA and IgG antibodies in breast milk,5 and 9 weeks after vaccination with 3 doses of the protein subunit vaccine Abdala,compared to those found in breast milk from COVID-19-recovered women,collected at least 40 days after the infection.Methods:SARS-CoV-2 spike RBD-specific IgA and IgG antibodies were semi-quantified by indirect ELISA,using a homemade standard generated by pooling twenty breast milk samples with high absorbance values according to preliminary data.The validity of the standard curves was proved following the European Medicines Agency Guideline.Two breast milk samples from 2 unvaccinated women who had not been infected with COVID-19 were included as negative controls.Potentially neutralizing antibodies was assessed by a SARS-CoV-2 surrogate virus neutralization test.Results:High levels of anti-RBD IgA antibodies were detected in breast milk samples 9 weeks after vaccination and anti-RBD IgG antibodies rise from the fifth to the ninth week.In the post-COVID-19 time that was evaluated,the IgG-type response was notably higher compared to both post-vaccination periods.Neutralizing antibody titers were similar in breast milk from vaccinated and COVID-19 recovered women.Conclusions:This is the first report about the immune response in breast milk after the administration of a COVID-19 protein subunit vaccine,which could provide analogous protection to that conferred by SARS-CoV-2 infection.This implies a potential passive immunity that breastfed infants receive from their mothers vaccinated with Abdala.

关键词： Abdala vaccine IgA IgG Neutralizing antibody titers SARS-CoV-2

Arthrospira maxima(Spirulina)prevents endoplasmic reticulum stress in the kidney through its C-phycocyanin

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2021年第7期22卷 603-608页

作者： Placido ROJAS-FRANCO Margarita FRANCO-COLÍN Vanessa BLAS-valdivia María Estela MELENDEZ-CAMARGO Edgar CANO-EUROPA Laboratorio de Metabolismo I Departamento de FisiologíaEscuela Nacional de Ciencias BiológicasInstituto Politécnico NacionalMexico City 07738Mexico Laboratorio de Neurobiología Departamento de FisiologíaEscuela Nacional de Ciencias BiológicasInstituto Politécnico NacionalMexico City 07738Mexico Laboratorio de Toxicologia Hepática y Renal Departamento de FarmaciaEscuela Nacional de Ciencias BiológicasInstituto Politécnico NacionalMexico City 07738Mexico

Arthrospira maxima(Spirulina)is a cyanobacterium which is considered a nutraceutical because it has antioxidant,anti-inflammatory,and cytoprotective properties in different renal disease models(RodriguezSánchez et al... 详细信息

关键词： al. protective reticulum

Can the Interspinous Distance Predict Kyphosis in Conservative Treatment in Thoracolumbar Burst Fracture? A Retrospective, Diagnostic Study

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Open Journal of Orthopedics 2016年第1期6卷 10-15页

作者： Robert Meves osmar Avanzi Orthopedics Department Faculty of Medical Sciences Santa Casa Spine Center Sao Paulo Brazil

Study Design: Retrospective, diagnostic study. Objective: To verify if the interspinous distance is able to predict the risk for kyphotic collapse in thoracolumbar burst fractures treated conservatively without neurological deficit. Summary of Background Data: In patients with thoracolumbar burst fractures, the association between the amount of comminution, by using load-sharing classification (LSC), and kyphotic collapse is presented in the literature. However, LSC does not include the interspinous distance as an indirect sign to suggest biomechanical instability due to posterior ligamentous disruption in these patients in order to predict kyphotic collapse. Methods: We added the interspinous distance to the load-sharing classification (MLSC) in 50 consecutive patients with thoracolumbar burst fractures (according to Denis criteria) treated conservatively. Results: The LSC score was correlated to kyphotic collapse in the patients treated with TLSO (r = 0.312, p = 0.027;Spearman test;A = 0.668). The MLSC was similarly correlated to kyphotic collapse among TLSO-treated patients (r = 0.295, p = 0.038;Spearman test;A = 0.652). Conclusions: The interspinous distance did not contribute to the identification of worse radiographic outcomes, represented by the kyphotic collapse. This may suggest that the amount of comminution pointed out by the LSC is enough and more important than the interspinous opening in order to predict kyphotic collapse in thoracolumbar burst fractures. Possibly, the interspinous distance is much too heterogenous and multifactorial to be useful, since it reflects vertebral body height, preinjury anatomy, as well as posterior element disruption.

关键词： Spine Spinal Fractures Trauma Severity Indices