Virus entéricos distintos de rotavirus y norovirus en menores de 5 años con gastroenteritis en Argentina, 2010-2021. Estudio descriptivo / Enteric viruses other than rotavirus and norovirus in children under 5 years of age with gastroenteritis in Argentina, 2010­2021. A descriptive study

Introducción. Los datos de frecuencia de los adenovirus entéricos, sapovirus y astrovirus en casos de gastroenteritis aguda esporádica en Argentina son escasos. Métodos. Diseño descriptivo sobre una selección de muestras de heces de menores de 5 años con diarrea remitidas durante el período 2010-2021, con resultado previo negativo para rotavirus y norovirus. Se estudió la presencia de adenovirus entéricos, sapovirus y astrovirus por métodos moleculares, con posterior genotipificación de las muestras positivas. Resultados. De 574 muestras seleccionadas, en 226 (39,4 %) se identificó al menos uno de los virus estudiados. En particular, se detectaron adenovirus, sapovirus y astrovirus en el 30,7 %, el 5,6 % y el 3,1 %, respectivamente. El adenovirus 41, los sapovirus GI.1 y GI.2, y el astrovirus 1 fueron los más frecuentemente detectados. Se identificaron dos muestras con astrovirus no clásicos. Conclusiones. A pesar de ser menos frecuentes, estos enteropatógenos son responsables de un número considerable de episodios de diarrea esporádica. Por lo tanto, su estudio y vigilancia contribuye significativamente a reducir la brecha de casos no diagnosticados.

Introduction. Data on the frequency of enteric adenoviruses, sapoviruses, and astroviruses in cases of sporadic acute gastroenteritis in Argentina are scarce. Methods. Descriptive design of a selection of fecal samples of children with diarrhea younger than 5 years referred between 2010 and 2021, with a previous negative result for rotavirus and norovirus. The presence of enteric adenovirus, sapovirus, and astrovirus was tested by molecular methods, with subsequent genotyping of positive samples. Results. At least 1 of the tested viruses was detected in 226 (39.4%) of the 574 selected samples. Specifically, adenovirus, sapovirus, and astrovirus were detected in 30.7%, 5.6%, and 3.1% of the samples, respectively. The most frequent viruses detected were adenovirus 41, sapoviruses GI.1 and GI.2, and astrovirus 1. Non-classic astroviruses were detected in 2 samples. Conclusions. Despite being less frequent, these enteropathogens are responsible for a large number of sporadic diarrhea events. Therefore, their study and surveillance contribute significantly to reduce the gap of undiagnosed cases.

Construction of recombinant adenovirus expression vector of avian reovirus σC protein and its effect on proliferation of hepatocellular carcinoma cells / 中国生物制品学杂志

@#Objective To construct the recombinant adenovirus vector pAd-σC for the expression of avian reovirus(ARV)aC protein and to detect its effects on the proliferation of hepatocellular carcinoma cells,in order to build up a basis for the development of novel anti-tumor vaccines.Methods The recombinant shuttle vector pShuttle-σC was constructed by PCR amplification of ARV σC gene,and then transformed into competent BJ5183 cells containing the adenovirus vector pAdessy-1.The recombi-nant adenovirus vector pAd-σC was obtained by homologous recombination,and the virus was packaged in HEK293 cells.The virus titer was measured by TCID_(50),the expression of σC protein was determined by Western blot and ELISA,and the effect of virus on the proliferation of human hepatocellular carcinoma cells SMMC7721 was detected by CCK-8 assay.Results The recombinant shuttle vector pShuttle-σC was confirmed to be constructed correctly by double enzyme digestion and sequen-cing,and the recombinant adenovirus vector pAd-σC was constructed correctly as identified by colony PCR.σC protein was successfully expressed in hepatocellular carcinoma cells SMMC7721.The recombinant adenovirus Ad-σC had a titer of 10~(7.5)/0.1 mL,which inhibited the proliferation of hepatocellular carcinoma cells SMMC7721.Conclusion The recombinant adenovirus vector pAd-trC containing ARV σC gene was successfully constructed,and its inhibitory effect on tumor cell proliferation was preliminarily analyzed,which lays a foundation for revealing the molecular mechanism of ARV oncolytic effect and further developing novel anti-tumor biological preparation.

Experimental study on treatment of severe limb ischemia with Ad-hVEGF-hHGF gene / 实用医学杂志

Objective To explore the role and efficacy of VEGF and HGF gene adenovirus vector in promoting angiogenesis in ischemic tissue.Methods 84 Kunming mice were randomly divided into sham group,control group,VEGF group,HGF group and VEGF+HGF group,and the left lower limb ischemia model was established.The blood supply of ischemic tissue was observed by rheometer,and the expression levels of VEGF and HGF in each group were detected by Western Blot and ELISA.Immunohistochemical staining was used to detect angiogenesis(CD31,SMA)in ischemic tissues.Safety was assessed by side effects during treatment in mice.Results After the successful modeling,the blood flow velocity of the left lower limb in each group decreased significantly.On the 7th day after operation,the blood flow of the left lower limb in each group was significantly better than that on the 0th day after operation(P<0.05),and the blood flow of the left lower limb in Ad-VEGF-HGF group was significantly better than that in other groups(P<0.05).On the 28th day after operation,the blood flow of the left lower limb in Ad-VEGF-HGF group gradually stabilized,the blood flow in Ad-VEGF-HGF group was significantly better than that in other groups,and both VEGF group and HGF group were significantly better than the control group(P<0.05).On the 7th,14th,and 28th days following surgery,HGF and VEGF protein levels in the Ad-HGF,Ad-VEGF,and Ad-VEGF-HGF groups were substantially greater than those in the control group(P<0.05).The expression level in the Ad-VEGF-HGF group peaked on the 14th day(all P<0.001)and subsequently declined to preoperative levels on the 28th day after operation.Conclusion Ad-VEGF-HGF gene injection can effectively boost VEGF and HGF protein expression and rapidly reach the relative peak level,encour-aging angiogenesis after lower limb ischemia,increasing blood flow,and improving lower limb circulation.

Construction of recombinant adenovirus vector of Uhrf1 gene and its role in DNA damage repair of cardiomyocytes / 中国病理生理杂志

AIM:To construct a recombinant adenovirus vector carrying the mouse ubiquitin-like with plant homeodomain and RING finger domains 1(Uhrf1)gene,validate the expression of Uhrf1 in neonatal mouse cardiomyo-cytes and explored its role in hydrogen peroxide(H2O2)-induced DNA damage.METHODS:The mouse Uhrf1 gene cod-ing sequence was amplified by polymerase chain reaction(PCR),digested,and inserted into the pADM-CMV-C-FH vec-tor to create the recombinant adenoviral plasmid ADM-Uhrf1.Following transfection into HEK293T cells,we generated re-combinant adenoviral particles,amplified,purified,and determined the titer.Neonatal mouse cardiomyocytes were infect-ed at an multiplicity of infection(MOI)of 50,UHRF1 protein expression was validated via Western blot and immunofluo-rescence staining.H2O2-induced DNA damage was explored along with adenovirus-mediated Uhrf1 overexpression to inves-tigate its role in DNA damage repair.RESULTS:ADM-Uhrf1 virus titer,determined by capsid immunofluorescence as-say,was 1.8×1013 pfu/L.Western blot confirmed a significant increase in UHRF1 protein expression(P＜0.05),with im-munofluorescence indicating predominant nuclear localization.Uhrf1 overexpression effectively inhibited the expression of the DNA damage marker,phosphorylated H2AX protein(γH2AX)(P＜0.01).CONCLUSION:We successfully con-structed a recombinant adenoviral vector carrying the mouse Uhrf1 gene,facilitating Uhrf1 overexpression in neonatal mouse cardiomyocytes.Furthermore,this overexpression effectively alleviated DNA damage in cardiomyocytes.

Expression and identification of recombinant adenovirus type 5-Norovirus GⅡ.4-VP1 virus-like particles / 中国生物制品学杂志

@#Objective To express and identify recombinant adenovirus type 5-Norovirus(NoV)GⅡ.4-VP1 virus-like particles(VLPs)in 293T cells. Methods The recombinant adenovirus plasmids pAd5-eGFP and pAd5-NoV-GⅡ.4-VP1 were transfected into 293T cells respectively,and the recombinant adenovirus rAd5-eGFP and rAd5-NoV-GⅡ.4-VP1 were rescued. The rAd5-eGFP was subcultured in 293T cells to verify the function of the vector. The rAd5-NoV-GⅡ.4-VP1 was subcultured in293T cells,expressed and purified,and then NoV-GⅡ.4-VLP was formed by self-assembly,which was detected by Western blot,ELISA and observed by transmission electron microscope. Results The green fluorescence of the recombinant adenovirus rAd5-eGFP of various generations was observed under microscope,and the brightness increased with the increase of generations. NoV-GⅡ.4-VP1 protein was expressed in the harvested solution of recombinant adenovirus rAd5-NoV-GⅡ.4-VP1 of various generations,with a relative molecular mass of about 58 900. NoV-GⅡ.4-VLP showed specific binding to the rabbit anti-NoV-GⅡ.4-VP1 serum;it had similar conformation to natural NoV virus particles and can effectively identify NoV receptors in volunteer saliva samples;microscopic observation showed that the morphology was complete and spherical,with a diameter of 43. 5 — 58. 3 nm,while there were a few protrusions on the surface of the particles,which might be the P domain exposedon the particle surface during self-assembly of VP1. Conclusion The expressed recombinant adenovirus NoV-GⅡ. 4-VLP has complete VLP structure and good specificity,and is expected to be used in the related research of NoV adenovirus vector vaccine.

Human adenovirus associated with severe cold agglutinin syndrome: a rare complication in Pediatrics / Adenovírus humano associado à síndrome da aglutinina fria grave: uma complicação rara em Pediatria

ABSTRACT Objective: The objectives of this study were to describe the first pediatric case of cold agglutinin syndrome (CAS) triggered by human adenovirus and review the literature. Case description: This case report involves a previously healthy, 2½-year-old female child with human adenovirus isolated in a nasal swab. At 72 h after admission, the patient progressed to a severe episode of anemia (hemoglobin level: 2.6 g/dL). The laboratory findings were consistent with CAS. The patient received blood transfusion, vitamin supplementation, adequate hydration, and thermal protection. At her last follow-up, 1 year after her initial presentation, she remains clinically well without signs of hemolysis. Comments: While severe CAS is extremely uncommon in the pediatric emergency department, human adenovirus infection is a common illness in pediatrics. Recently, the adenovirus has been associated with new complications (acute hepatitis and fulminant liver failure). Pediatric physicians and hematologists should be aware of unusual evolution, signs, and symptoms of this infection that warrant more urgent medical attention. In this case, the hematologic complication suspicion was the key to early diagnosis and adequate management.

RESUMO Objetivo: Descrever o primeiro caso pediátrico de síndrome da crioaglutinina desencadeado por adenovírus humano e revisar a literatura. Descrição do caso: Paciente do sexo feminino, dois anos e seis meses, previamente hígida e diagnosticada com adenovírus humano isolado em swab nasal. Após 72 horas da admissão, a paciente evoluiu com quadro de anemia grave (hemoglobina de 2,6 g/dL). Os achados laboratoriais foram compatíveis com síndrome da crioaglutinina. A paciente recebeu transfusão de concentrado de hemácias, suplementação vitamínica, hidratação adequada e proteção térmica. Em seu último retorno ambulatorial, um ano após a apresentação inicial, permanecia clinicamente bem, sem sinais de hemólise. Comentários: Enquanto a síndrome da crioaglutinina grave é extremamente incomum na emergência pediátrica, a infecção por adenovírus humano é um quadro comum na infância. Recentemente, o adenovírus tem sido associado a novas complicações, e pediatras e hematologistas devem ficar atentos à possibilidade de uma evolução incomum dessa infecção e dos sinais e sintomas que possam necessitar de atenção urgente. No caso apresentado, a suspeita da complicação hematológica foi a chave para o diagnóstico precoce e seu manejo adequado.

Fecal leukocyte frequency in children with acute viral gastroenteritis: a single-center experience

SUMMARY OBJECTIVE: Our objective was to determine the frequency of rotavirus, adenovirus, and rota-adenovirus co-infections and investigate the fecal leukocyte rate associated with these infections in patients with gastroenteritis. METHODS: This is a retrospective study. We identified patients who were admitted to the pediatric emergency department with acute gastroenteritis and had their stool samples tested for rotavirus and/or adenovirus antigens. Among them, we determined the individuals who underwent stool microscopy tests on the same day and recorded their results. RESULTS: A total of 1,577 patients who underwent testing for rotavirus and/or adenovirus antigens in their stool samples were identified. Among these patients, 583 individuals had concurrent fecal microscopy results. The prevalence of solely rotavirus antigen positivity was 16.4%, solely adenovirus antigen positivity was 2.9%, and rota-adenovirus co-infections were detected in 1.8% of the children. The fecal leukocyte rates in children infected with rotavirus, adenovirus, and rota-adenovirus co-infections were 4.8, 13.3, and 88.9%, respectively. CONCLUSION: The presence of fecal leukocytes was detected at a high rate in cases of viral gastroenteritis, especially in rota-adenovirus co-infections. Therefore, clinicians should not consider only bacterial pathogens in the presence of fecal leukocytes.

The role of SPARCL1 in atherosclerotic plaque formation / 安徽医科大学学报

Objective @#To investigate the effect of cysteine rich acidic secretory protein like protein 1 (SPARCL1) on atherosclerosis (AS) plaque formation .@*Methods @#A case control study design was used , 394 patients with con firmed AS were selected as the case group , and 394 healthy medical examiners matched for age and gender were se lected as the control group . The expression level of serum SPARCL1 was determined by enzyme linked immunosor bent assay; immunohistochemistry was used to assess the expression level and localization of SPARCL1 protein in the AS plaque region , and the expression of SPARCL1 protein was also detected in the neutrophils and monocytes of peripheral blood of AS patients and normal controls; SPARCL1 overexpressing and the recombinant adenoviral vec tors were constructed to inhibit SPARCL1 overexpression and expression , and the effects of SPARCL1 on cell mi gration were ob served in the cell scratch assay using mouse macrophage cells (J774A.1) as target cells .@*Results@#Serum SPARCL1 levels in the AS patient group were lower than those in the healthy group ( P < 0.05 ) ; high SPARCL1 expression was detected in AS plaques and was mainly expressed in the cytoplasm of foamy cells; SPARCL1 expression levels in peripheral blood neutrophils and monocytes were lower than those in normal controls in AS patients (P < 0.05) ; recombinant SPARCL1 overexpression and inhibition of expression of adenovirus was successfully constructed; the cell migration rate was decreased in J774A.1 cells that inhibited SPARCL1 expression and increased in J774A.1 cells that overexpressed SPARCL1 ( P < 0.05) .@*Conclusion @#SPARCL1 is highly expressed in foam cells at the site of AS lesions , which may result from compensatory recruitment of peripheral blood monocytes and neutrophils , and SPARCL1 may be involved as a protective factors for blood vessels in inhibiting the development of AS plaques .

Construction of recombinant adenovirus expression vector of avian reovirus σC protein and its effect on proliferation of hepatocellular carcinoma cells / 中国生物制品学杂志

@#Objective To construct the recombinant adenovirus vector pAd-σC for the expression of avian reovirus(ARV)aC protein and to detect its effects on the proliferation of hepatocellular carcinoma cells,in order to build up a basis for the development of novel anti-tumor vaccines.Methods The recombinant shuttle vector pShuttle-σC was constructed by PCR amplification of ARV σC gene,and then transformed into competent BJ5183 cells containing the adenovirus vector pAdessy-1.The recombi-nant adenovirus vector pAd-σC was obtained by homologous recombination,and the virus was packaged in HEK293 cells.The virus titer was measured by TCID_(50),the expression of σC protein was determined by Western blot and ELISA,and the effect of virus on the proliferation of human hepatocellular carcinoma cells SMMC7721 was detected by CCK-8 assay.Results The recombinant shuttle vector pShuttle-σC was confirmed to be constructed correctly by double enzyme digestion and sequen-cing,and the recombinant adenovirus vector pAd-σC was constructed correctly as identified by colony PCR.σC protein was successfully expressed in hepatocellular carcinoma cells SMMC7721.The recombinant adenovirus Ad-σC had a titer of 10~(7.5)/0.1 mL,which inhibited the proliferation of hepatocellular carcinoma cells SMMC7721.Conclusion The recombinant adenovirus vector pAd-trC containing ARV σC gene was successfully constructed,and its inhibitory effect on tumor cell proliferation was preliminarily analyzed,which lays a foundation for revealing the molecular mechanism of ARV oncolytic effect and further developing novel anti-tumor biological preparation.

Epidemiological characteristics and influencing factors of adenovirus-associated acute conjunctivitis in Shenzhen，2014‒2022 / 上海预防医学

ObjectiveTo investigate the epidemic characteristics and influencing factors of acute conjunctivitis caused by human adenovirus（HAdv）in Yantian District of Shenzhen City， Guangdong Province from 2014 to 2022， and to provide evidence for formulating effective prevention and control measures. MethodsDescriptive epidemiology was used to analyze the epidemiological characteristics of acute hemorrhagic conjunctivitis （AHC） cases reported from the Chinese disease prevention and control information system. Etiological characteristics of laboratory-confirmed cases were analyzed， and a case-control study method of test-negative design （TND） was conducted as well. According to the result of HAdv detection， analysis was used to identify the influencing factors of morbidity. ResultsA total of 1 005 AHC cases were reported in Yantian District， Shenzhen City from 2014 to 2022， with an average annual incidence rate of 49.49/105. The incidence rate ranged from 4.67/105 to 117.28/105. The peak incidence occurred from July to October each year， with a male-to-female ratio of 1.42∶1. The median （P25，P75） age of onset was 29（12，40） years. A total of 716 eye swabs were collected for etiological detection from 2014 to 2022. HAdv positive detection rate was 36.45% （263/716）， Cox 24v positive detection rate was 0.28% （2/716）， while EV70 was not detected. The longest viral shedding time in eye swabs was 10 days， with a median of 2 days. The highest HAdv positive detection rate （47.47%） was observed when the sampling-to-onset interval was 4‒5 days， and the difference was statistically significant （P<0.05）， with a trend of first increasing and then decreasing. Multivariate logistic regressing analysis showed that aged 18‒ years， and average temperature higher than 24.90 ℃ 3 days before onset （P<0.05） were the risk factors for acute HAdv conjunctivitis. ConclusionAHC in Yantian District， Shenzhen City showed a low level of prevalence from 2014 to 2022， with HAdv being the predominant pathogen. The peak period of viral shedding occurred on the 4th to 5th day after symptom onset， suggesting the importance of adherence to strict home isolation for infected persons. Aged18‒ years and average temperature increased 3 days before onset are associated with an increased risk of adenoviral conjunctivitis. It is recommended to strengthen personal protection and keep doing a good job of AHC surveillance and early warning， so as to timely prevent the outbreaks of AHC.

A pair of siblings with congenital short bowel syndrome and intestinal malrotation caused by a novel variation in the CLMP gene / 中华围产医学杂志

This paper reports a pair of siblings with congenital short-bowel syndrome (CSBS) complicated with intestinal malrotation. Case 1 was born with a birth weight of 2 550 g and a length of 48 cm. On September 10, 2017, emergency Ladd's procedure and appendectomy were performed on the infant 23 days after birth due to intestinal obstruction at the Women and Children's Hospital, School of Medicine, Xiamen University. The small intestine of the infant had a total length of 65 cm. Postoperative enteral and parenteral nutrition supports were provided for six months. Whole exome sequencing revealed a homozygous variant (NM 024769; nucleotide deletion in the exon 3-5) in the CLMP gene (chr11:122953792-122955421), with the parents being the heterozygous carriers but without phenotype. Case 2, the younger sibling of Case 1, was born in the same hospital on March 20, 2020, with a birth weight of 2 932 g and a body length of 49 cm. Prenatal single-gene sequencing on the amniotic fluid identified the same gene variation as his sister's. The baby boy received Ladd's procedure and appendectomy on the second day after birth which found the length of his small intestine was 51 cm. Full enteral nutrition was achieved six months after the operation. Both cases were followed up for 12 months. The body weight and length of Case 1 were both below the first percentile (< P1). The body weight of Case 2 was 8.03 kg ( P3- P5) and the length was 76.0 cm ( P25- P50).

Genetic evolution of Penton base, Hexon and Fiber genes of human adenovirus 3 in a clustered fever outbreak in Kunming / 中华微生物学和免疫学杂志

Objective:To perform adenovirus detection and genetic evolutionary analysis on specimens from a fever outbreak in Kunming city.Methods:Pharyngeal swabs from typical febrile patients were collected and tested for nucleic acids of 30 common respiratory pathogens using TaqMan Array Card technology. The full-length sequences of three important genes of adenovirus, Penton base, Hexon and Fiber, were amplified, sequenced and typed using Nanopore high-throughput sequencing. A phylogenetic tree was constructed. Molecular variations and genetic evolution of the three genes were analyzed.Results:Five specimens were collected and all of them tested positive for adenovirus and Haemophilus influenzae. The sequences of the full-length coding regions of the Penton base, Hexon and Fiber genes were obtained by Nanopore sequencing. The homology of the three gene sequences in the five specimens was 100.0%, 99.9%-100.0% and 100.0% in nucleotide sequences, and 100.0% in amino acid sequences. The three genes in the specimens had the highest homology with those of the reference strain of human adenovirus type 3 (HAdV3, accession number: AY599834) in nucleotide sequences, which was 98.6%, 98.7% and 98.9%, respectively. Results of the phylogenetic analysis of the three genes were basically consistent. These Kunming strains were clustered into an independent clade with the reference HAdV3 strain and had a distant relationship with the strains isolated in foreign countries and Taiwan, China in the early years. They were closely related to the domestic and foreign strains in recent years and highly homologous to the 2019 Japanese strain (accession: LC703523) and the Guangzhou strain (accession: MZ540961). Compared with the reference strain, these Kunming strains had five amino acid variations in Penton base, 10 in Hexon and 11 in Fiber. Conclusions:All of the adenovirus strains isolated in this outbreak belong to P3H3F3 type based on the full-length sequences of Penton base, Hexon and Fiber genes. They share high homology with the domestic and foreign HAdV3 strains, including the reference strain. Compared with the reference strain, several amino acid mutations are identified in these Kunming strains, and most of them are in the high variability region or functional regions. M7L in the Hexon protein is an unique amino acid mutation site of Kunming strains.

Bronquiolitis obliterante postinfecciosa en niños: serie de casos en un hospital pediátrico de Perú / Postinfectious bronchiolitis obliterans in children: case series at a pediatric hospital in Peru

Resumen Introducción: La bronquiolitis obliterante postinfecciosa es una enfermedad pulmonar poco frecuente; existen limitados reportes en Sudamérica. Caso clínico: En esta serie se reportan 10 pacientes con esta enfermedad diagnosticados en el Instituto Nacional de Salud del Niño-Breña (Lima-Perú). La mediana de edad al diagnóstico fue de 19 meses. Todos los pacientes presentaron el antecedente de infección respiratoria aguda grave. Los síntomas más frecuentes fueron tos, dificultad respiratoria, sibilancias e hipoxemia; el patrón de atenuación en mosaico fue la característica más frecuente en la tomografía. Todos tenían serología positiva para adenovirus. Se administró tratamiento con pulsos de metilprednisolona, azitromicina, hidroxicloroquina y corticoides inhalados. Ningún paciente falleció durante el seguimiento. Conclusiones: En los niños previamente sanos con antecedente de infección respiratoria aguda grave y sintomatología obstructivo bronquial persistente se debe considerar el diagnóstico de bronquiolitis obliterante postinfecciosa. Este es el primer reporte en Perú con un régimen terapéutico adaptado a nuestra institución.

Abstract Background: Postinfectious bronchiolitis obliterans is a rare lung disease; there are limited reports in South America. Case report: We report 10 patients with this disease diagnosed at the Instituto Nacional de Salud del Niño-Breña (Lima-Peru). The median age at diagnosis was 19 months and all patients had a history of severe acute respiratory infection. The most frequent symptoms were cough, respiratory distress, wheezing, and hypoxemia. The mosaic attenuation pattern was the most frequent on the tomography. All the patients had positive serology for adenovirus. The treatment received was methylprednisolone pulses, azithromycin, hydroxychloroquine, and inhaled corticosteroids. No patient died during the follow-up. Conclusions: In previously healthy children with a history of severe acute respiratory infection and persistent bronchial obstructive symptoms, the diagnosis of postinfectious bronchiolitis obliterans should be considered. This is the first report in Peru with a therapeutic regimen adapted to our institution.

Hepatitis aguda de origen desconocido. Una serie de casos probables atendidos en un hospital pediátrico de referencia en Panamá

Introducción: Durante el año 2022 se objetivó un aumento de casos de hepatitis de origen desconocido en la población pediátrica. Su etiología a día de hoy todavía no ha sido esclarecida. Este estudio tiene como objetivo presentar la clínica y los resultados de los análisis de laboratorio de los pacientes con hepatitis atendidos en el Hospital del Niño Dr. José Renán Esquivel durante el año 2022.   Material y métodos: Estudio descriptivo de 10 pacientes pediátricos con criterios de hepatitis aguda de origen desconocido atendidos en nuestro centro durante el año 2022. Se ha llevado a cabo un análisis de las principales variables clínicas, analíticas, demográficas, vacunales y serológicas.   Resultados:  Se encontraron 10 pacientes, con una media de edad de 2,8 años. La clínica predominante ha sido la de ictericia, fiebre y clínica gastrointestinal. Analíticamente se ha detectado un aumento de los niveles de transaminasas así como de bilirrubina. Tan sólo un paciente contaba con historia de vacunación para el SARS-CoV-2. El principal agente etiológico identificado ha sido el adenovirus, encontrándose en el 40% de los casos.   Conclusiones: Los pediatras deben tener en cuenta el diagnóstico de hepatitis aguda de origen desconocido en pacientes con clínica de ictericia y fiebre, pudiendo asociar vómitos, diarrea, hepatomegalia, dolor abdominal y coluria, entre otros. La elevación de transaminasas (>500 U/L de AST o ALT) y bilirrubina debe aumentar el índice de sospecha. A pesar de que el principal agente etiológico parece guardar relación con el adenovirus, son necesarios más estudios para confirmar dicha hipótesis. (provisto por Infomedic International)

Introduction: During the year 2022 an increase in cases of hepatitis of unknown origin was observed in the pediatric population. Its etiology has not yet been clarified. This study aims to present the clinical and laboratory results of patients with hepatitis treated at the Hospital del Niño Dr. José Renán Esquivel during the year 2022.   Material and methods: Descriptive study of 10 pediatric patients with criteria of acute hepatitis of unknown origin seen in our center during the year 2022. An analysis of the main clinical, analytical, demographic, vaccination and serological variables was carried out.   Results: The final sample consisted of 10 patients, with a mean age of 2.8 years. The predominant clinical manifestations were jaundice, fever and gastrointestinal symptoms. Laboratory tests showed increased levels of transaminases and bilirubin. Only one patient had a history of vaccination for SARS-CoV-2. The main etiological agent identified was adenovirus, found in 40% of the patients studied.   Conclusions: Pediatricians should consider the diagnosis of acute hepatitis of unknown origin in patients with jaundice and fever, which may be associated with vomiting, diarrhea, hepatomegaly, abdominal pain and choluria, among others. Elevated transaminases (>500 U/L of AST or ALT) and bilirubin should increase the index of suspicion. Although the main etiological agent to date seems to be related to adenovirus, further studies are needed to confirm this hypothesis. (provided by Infomedic International)

Sobre la hepatitis aguda grave de etiología desconocida: la situación en México / About severe acute hepatitis of unknown etiology: the situation in Mexico

Introducción: en México, las hepatitis virales son de notificación epidemiológica obligatoria, pero no existe un sistema especial de vigilancia. La información disponible se limita a la distribución por edad y sexo. Ante la alerta de casos de hepatitis aguda grave de etiología desconocida, en la Unión Europea el Consejo Nacional de Vigilancia Epidemiológica (CONAVE) alertó al Sistema Nacional de Salud (SNS) para la atención y vigilancia de estos casos. Desarrollo: la hipótesis más convincente sobre la etiología está relacionada con una respuesta inmunitaria exacerbada que es mediada por superantígenos relacionados con la proteína espiga del SARS-CoV-2, activados por una infección por adenovirus que desencadena una respuesta de linfocitos T que provoca apoptosis de hepatocitos. Con base en la presentación clínica (niños menores de 16 años, con diarrea, dolor abdominal, ictericia, vómito e hipertransaminasemia) se han diseñado definiciones operacionales para su identificación y notificación al Sistema Nacional de Vigilancia Epidemiológica (SINAVE). Hasta junio del 2022, se han identificado 56 casos en México. Conclusiones: este brote de hepatitis representa un reto para el SINAVE. Es necesario incluir la identificación de adenovirus en el algoritmo diagnóstico de enfermedad respiratoria viral, implementar un sistema especial de vigilancia epidemiológica de hepatitis virales y sensibilizar a los profesionales sanitarios en el tema.

Introduction: In Mexico viral hepatitis requires mandatory epidemiological notification, but there is no special surveillance system. Available information is limited to distribution of cases by age and sex. Given the alert of cases of severe acute hepatitis of unknown etiology in the European Union, the National Council for Epidemiological Surveillance (Consejo Nacional de Vigilancia Epidemiológica) alerted the entire National Health System to care for and monitor these cases in Mexico. Development: The most convincing hypothesis is an exacerbated immune response mediated by superantigens related to the spike protein of SARS-CoV-2, activated by adenovirus infection that ends in a response of T lymphocytes that causes apoptosis of hepatocytes. Based on clinical presentation (children under 16 years of age, with diarrhoea, abdominal pain, jaundice, vomiting and increase in transaminases) the operational case definitions have been designed for their timely identification and notification to the National System of Epidemiological Surveillance (Sistema Nacional de Vigilancia Epidemiológica). Until June 2022, 56 cases have been identified in Mexico. Conclusions: This hepatitis outbreak represents a challenge for the National System of Epidemiological Surveillance. It is necessary to include the identification of adenovirus in the diagnostic algorithm for viral respiratory disease, to implement a special epidemiological surveillance system for viral hepatitis, and to sensitize health professionals on this subject.

Severe Acute Hepatitis: An Emerging Grave Illness in Children

Acute hepatitis of unknown origin in children has been recently described in the literature, and a case definition has also been proposed for this condition. The exact etiology is unknown and exclusion of infectious, metabolic, autoimmune and toxin mediated injuries is essential. Management for this condition is supportive, but some may require liver transplantation. Infection prevention and control practices are important as the etiology remains unidentified.

Progress in early recognition and treatment of severe adenovirus pneumonia in children / 中华实用儿科临床杂志

Adenovirus pneumonia is a common respiratory tract infection in children.Severe cases of adenovirus pneumonia have the characteristics of rapid onset, rapid progression and a panel of complications.Therefore, early recognition, diagnosis and treatment are particularly important.In recent years, studies on the pathogens, hosts, laboratory tests and biomarkers have provided new clinical clues for the early recognition and diagnosis of severe adenovirus pneumonia in children.There are currently no specific antiviral drugs for severe adenovirus pneumonia.Therefore, the main therapeutic strategies for adenovirus pneumonia are immune therapy and respiratory support.A large number of clinical studies have provided new ideas for standardizing therapeutic strategies and improving the prognosis of children.

Protective mechanism of RNA binding protein LIN28 on diabetic nephropathy / 局解手术学杂志

Objective To explore the protective mechanism of RNA binding protein LIN28 on diabetic nephropathy(DN).Methods LIN28 was overexpressed or knocked down by adenovirus in HEK 293T cells.The gene and functional signaling pathway significantly changed after overexpression of LIN28 were obtained through RNA Seq transcriptome sequencing and bioinformatics analysis.HEK 293T cells were divided into the Control group,the Treatment group,the Adv-LIN28-OE+D-ribose group and the Adv-LIN28-NC+D-ribose group in in vitro LIN28 overexpression studies.And HEK 293T cells were divided into the Control group,the Treatment group,the Adv-shRNA LIN28+D-ribose group and the Adv-shRNA NT+D-ribose group in in vitro LIN28 knockdown studies.ELISA was used to detect the levels of human advanced glycation end products(AGEs)of cells supernatants in the above groups.Western blot was used to detect the expression levels of RAGE,NF-κB and MMP-2 of cells in the above groups.Results The results of RNA-Seq transcriptome sequencing,GO analysis and KEGG analysis showed that overexpression of LIN28 resulted in a significant down-regulation of AGE-RAGE signaling pathway in HEK 293T cells(P<0.05).The results of ELISA showed that compared with the Control group,the cell in the Treatment group produced a large amount of AGEs(P<0.05);compared with the Treatment group,the AGEs level of cells in the Adv-LIN28-OE+D-ribose group was significantly decreased(P<0.05),while the AGEs level of cells in the Adv-shRNA LIN28+D-ribose group was increased(P>0.05).The results of Western blot showed that compared with the Control group,the expression levels of RAGE,NF-κB and MMP-2 of cells in the Treatment group were significantly increased(P<0.05);compared with the Treatment group,the expression levels of RAGE,NF-κB and MMP-2 of cells in the Adv-LIN28-OE+D-ribose group were significantly decreased(P<0.05),while the expression levels of RAGE,NF-κB and MMP-2 of cells in the Adv-shRNA LIN28+D-ribose group were significantly increased(P>0.05).Conclusion Overexpression of LIN28 by adenovirus at the cellular level in vitro can lead to significant differential expression of thousands of genes.In particular,it can inhibit the diabetes and complications-related AGE-RAGE signaling pathway,which is critical in the progression of DN disease,and play a role in protecting DN.

Stable expression of shRNA for the control of recombinant adenovirus replication

Preventing the replication of adenovirus could have practical uses, such as controlling infection with wild-type virus or in applications involving recombinant vectors. Mainly transient methods have been used to inhibit adenovirus replication, including siRNA or drugs. Here, we tested whether stable expression of shRNA designed to target hexon, Iva2, or pol can inhibit the replication of a recombinant adenoviral vector, Ad-LacZ (serotype 5, E1/E3 deleted), in 293T cells. Significant knockdown correlating with reduced Ad-LacZ replication was achieved only when hexon was targeted. Cell sorting and isolation of cellular clones further accentuated knockdown of the hexon transcript, reduced protein levels by more than 90%, and diminished adenovirus production. As visualized by transmission electron microscopy, the cellular clone expressing the hexon-specific shRNA yielded 89.2% fewer particles compared to the parental 293T cells. Full scale production followed by purification revealed a 90.2% reduction in Ad-LacZ biological titer. These results support the notion that stable expression of shRNA can be used as a means to control adenovirus replication.

Influencia de la seropositividad contra adenovirus-36 sobre riesgo de obesidad y resistencia a la insulina en población infanto-juvenil de la Región de la Araucanía / Influence of adenovirus 36 seropositivity on the risk of obesity and insulin resistance in a population of children and adolescents from the Región de la Araucanía

La infección previa por el adenovirus-36 (Ad-36) se ha asociado con el proceso adipogénico y el control glicémico en modelos experimentales de cultivos celulares y animales. En humanos, la presencia de anticuerpos contra Ad-36 ha mostrado aumentar el riesgo de obesidad y, paradójicamente, mejorar el control glicémico en diferentes poblaciones. Se evaluó la influencia de la seropositividad contra Ad-36 sobre riesgo de obesidad, el perfil lipídico y glicémico en una población de niños en edad escolar. Métodos: Doscientos ocho individuos de entre 9 y 13 años se agruparon según estado nutricional como normopeso (IMC z-score de -1 a +1), con sobrepeso (IMC z-score de +1 a +2) y con obesidad (IMC z-score > +3). Se evaluaron medidas antropométricas, desarrollo puberal según Tanner y parámetros bioquímicos (perfil lipídico, glucemia e insulina) y la seropositividad contra Ad-36. Se determinó la resistencia a la insulina (RI) según criterio para la población infantil chilena. La seropositividad contra Ad-36 se determinó mediante ELISA. Resultados: Hubo una alta prevalencia de sobrepeso/obesidad en la población de estudio. La seropositividad contra Ad-36 fue del 5,4% en el grupo total, pero no se observó una asociación con el estado nutricional. No se encontró correlación entre la seropositividad contra Ad-36 y los parámetros del perfil lipídico. La insulina y la HOMA-RI fueron significativamente más bajas en el grupo Ad-36 (+) (p<0,001), no habiendo sido reportados casos de RI en el grupo Ad-36 (+) en nuestra población. Conclusiones: Nuestros resultados sugieren que la infección previa por el adenovirus-36 afecta la secreción de insulina y la resistencia a la insulina, como se ha descrito anteriormente, sin embargo, no se observa correlación con el desarrollo de la obesidad infantil en la población pediátrica del sur de Chile.

Previous infection with Adenovirus-36 (Ad-36) has been associated with adipogenic process and glycemic control in experimental models of cell culture and animals. In humans, the presence of antibodies against Ad-36 has been shown to increase the risk of obesity and, paradoxically, improve glycemic control in different populations. The influence of Ad-36 seropositivity on obesity risk, lipid and glycemic profile was evaluated in a population of school-age children. Methods: Two hundred eight individuals aged 9 to 13 years were grouped according to their nutritional status as normal weight (BMI z-score from -1 to +1), overweight (BMI z-score from +1 to +2) or obese (BMI z-score from -1 to +1). z-score > +3). Anthropometric measurements, pubertal development according to Tanner stage, biochemical parameters (lipid profile, glycemia and insulin) and seropositivity against Ad-36 were evaluated. Insulin resistance (IR) was determined according to criteria for the Chilean child population. Seropositivity against Ad-36 was determined by ELISA. Results: There was a high prevalence of overweight/obesity in the study population. Seropositivity against Ad-36 was 5.4% in the total group, but no association with nutritional status was observed. No correlation was found between Ad-36 seropositivity and lipid profile parameters. Insulin and HOMA-RI were significantly lower in the Ad-36 (+) group (p<0.001), and no cases of RI were reported in the Ad-36 (+) group in our population. Conclusions: Our results suggest that previous adenovirus-36 infection affects insulin secretion and insulin resistance, as previously described, however, no correlation is observed with the development of childhood obesity in the pediatric population. from southern Chile.