Association of gene polymorphisms of MyD88 and TICAM1 and their interactions with community-acquired pneumonia in children / 中国当代儿科杂志

OBJECTIVES@#To investigate the association of single nucleotide polymorphisms (SNPs) of myeloid differentiation factor 88 (MyD88) and Toll-like receptor adaptor molecule 1 (TICAM1) and their interactions with community-acquired pneumonia (CAP) in children.@*METHODS@#Improved multiple ligase detection reaction assay was used for detecting the polymorphisms of nine tagging SNPs of the MyD88 and TICAM1 genes in 375 children with CAP who attended the Department of Pediatrics of the Second Affiliated Hospital of Yan'an University Medical School from August 2015 to September 2017 and 306 healthy children who underwent physical examination. A logistic regression analysis was used to evaluate the association between the distribution of genotypes and their interactions with CAP in children.@*RESULTS@#The polymorphism of the TICAM1 gene at rs11466711T/C locus was closely associated with the susceptibility to CAP in children (P<0.05). The AA genotype of rs35747610G/A locus significantly reduced risk of sepsis in children with CAP (P<0.05). The AA genotype of rs6510826G/A locus was significantly associated with the increase in C-reactive protein level in children with CAP (P<0.05). The GG genotype of the MyD88 gene at rs7744A/G locus significantly increased the risk of respiratory failure and circulatory failure (P<0.05). The multiplicative interactions between MyD88 gene rs7744A/G and TICAM1 gene rs11466711T/C, rs2292151G/A, rs35299700C/T, and rs35747610G/A loci were significantly associated with the susceptibility to CAP, the severity of CAP, and the risk of sepsis in children (P<0.05).@*CONCLUSIONS@#The gene polymorphisms of MyD88 and TICAM1 and their interactions are closely associated with CAP in children, with a synergistic effect on the development and progression of CAP in children.

Network pharmacological analysis and experimental study of Pulsatilla chinensis against inflammatory injury caused by pneumonia in mice infected with influenza virus FM_1 / 中国中药杂志

Network pharmacology and the mouse model of viral pneumonia caused by influenza virus FM_1 were employed to explore the main active components and the mechanism of Pulsatilla chinensis against the inflammatory injury of influenza virus-induced pneumonia. The components and targets of P. chinensis were searched from TCMSP, and the targets associated with influenza virus-induced pneumonia were searched from GeneCards. The common targets between P. chinensis and influenza virus-induced pneumonia were identified with Venn diagram established in Venny 2.1. The herb-component-disease-target(H-C-D-T) network was constructed by Cytoscape 3.7.2. The above data were imported into STRING for PPI network analysis. Gene Ontology(GO) enrichment and KEGG pathway enrichment were performed with DAVID. BALB/cAnN mice were infected with the influenza virus FM_1 by nasal drip to gene-rate the mouse model of pneumonia. Immunohistochemistry was adopted to the expression profiling of inflammatory cytokines in the lung tissues of mice in the blank group, model group, and P. chinensis group 1, 3, 5, and 7 days after infection. The pathological changes of lung and trachea of mice in blank group, model group, and P. chinensis group were observed with light microscope and scanning electron microscope at all the time points. The network pharmacological analysis indicated that 9 compounds of P. chinensis were screened out, with a total of 57 targets, 22 of which were overlapped with those of influenza virus-induced pneumonia. A total of 112 GO terms(P<0.05) were enriched, including 81 terms of biological processes, 11 terms of cell components, and 20 terms of molecular functions. A total of 53 KEGG signaling pathways(P<0.05) were enriched, including TNF signaling pathway, influenza A signaling pathway, NF-κB signaling pathway, MAPK signaling pathway and other signaling pathways related to influenza/inflammation. In the P. chinensis group, the expression of TNF-α and IL-1 in the lung tissue was down-regulated on the 3 rd day after infection, and that of IL-6 in the lung tissue was down-regulated on the 5 th day after infection. Light microscopy and scanning electron microscopy showed that P. chinensis significantly alleviated the pathological damage of lung and trachea compared with the model group. This study reflects the multi-components, multi-targets, and multi-pathways of P. chinensis against influenza virus-induced pneumonia. P. chinensis may reduce the production of proinflammatory cytokines and mediators and block the pro-inflammatory signaling pathways to alleviate viral pneumonia, which provides reference for future research.

A novel frameshift mutation of Chediak-Higashi syndrome and treatment in the accelerated phase

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive immunodeficiency disease characterized by frequent infections, hypopigmentation, progressive neurologic deterioration and hemophagocytic lymphohistiocytosis (HLH), known as the accelerated phase. There is little experience in the accelerated phase of CHS treatment worldwide. Here, we present a case of a 9-month-old boy with continuous high fever, hypopigmentation of the skin, enlarged lymph nodes, hepatosplenomegaly and lung infection. He was diagnosed with CHS by gene sequencing, and had entered the accelerated phase. After 8 weeks of therapy, the boy had remission and was prepared for allogenic stem cell transplantation.

Medicina genómica aplicada a la neumonía aguda comunitaria: [revisión] / Genomic medicine applied to acute community acquired pneumonia: [review]

Las infecciones del tracto respiratorio inferior constituyen un enorme flagelo para la humanidad. La neumonía aguda comunitaria es la principal enfermedad respiratoria por frecuencia y severidad. A pesar de los avances de la medicina moderna, su morbilidad y mortalidad permanecen prácticamente incambiadas.La respuesta ante un agravio infeccioso es estrictamente individual al estar influida por la estructura genética del huésped. La medicina genómica procura personalizar y optimizar el diagnóstico, pronóstico y tratamiento mediante el reconocimiento de la influencia que ejercen determinadas variantesgenéticas, denominadas polimorfismos, en la susceptibilidad y evolución de las diversas patologías. Los polimorfismos genéticos son capaces de modificar el riesgo de padecer determinadoevento o suceso en una enfermedad específica por lo cual su reconocimiento permite personalizar la interacción entre ambiente y huésped. En el presente artículo se describen los polimorfismos que están asociados positivamente conla evolución de la neumonía aguda comunitaria y qué aplicaciones clínicas podría tener la medicina genómica.

As infecções do trato respiratório inferior são um importante problema para a humanidade sendo a pneumonia aguda comunitária a principal doença respiratória por sua frequência e gravidade. Apesar dos avanços da medicina moderna sua morbidade e mortalidade permanecem praticamente inalteradas. A resposta ante um ataque infeccioso é estritamente individual por estar sujeita à estrutura genética do hóspede. A medicina genômica busca personalizar e otimizar o diagnóstico,prognóstico e tratamento reconhecendo a influencia que exercem determinadas variantes genéticas, denominadas polimorfismos, sobre a suscetibilidade e a evolução das diferentes patologias.Os polimorfismos genéticos são capazes de modificar o risco de sofrer determinado evento em uma doença específica pelo qual seu reconhecimento permite personalizar a interação entre ambiente e hóspede. Neste artigo os polimorfismos que estão associados positivamente com a evolução da pneumonia aguda comunitária e as possíveis aplicações clínicas da medicina genômica são descritos.

Lower respiratory tract infections constitute a serious problem for humanity. Community-acquired pneumonia is the main respiratory disease due to frequency and severity. Inspite of progress made by modern medicine, mortality and morbility rates remain unchanged. Response to an infectious attack is strictly personal as it is influenced by the hostÆs genetic structure. Genomic medicine aims to personalize and optimize diagnosis, prognosis and treatment by acknowledging the influence of certain genetic variations, called polymorphisms,on susceptibility and the evolution of several pathologies. Genetic polymorphisms are able to modify the risk of suffering a certain event or episode in a specific disease and being aware of this enables personalizing the interaction between the environment and the host. The present study describes polymorphisms that are positively associated to the evolution of acute-community acquired pneumoniaand the possible clinical applications by genomic medicine.

Doença granulomatosa crônica autossômica: relato de caso e análise genético-molecular de dois irmãos brasileiros / Autosomal chronic granulomatous disease: case report and mutation analysis of two Brazilian siblings

OBJETIVO: Relatar dois casos de irmãos com doença granulomatosa crônica. A doença granulomatosa crônica é uma imunodeficiência primária caracterizada por atividade microbicida deficiente. Mutações no gene que codifica a proteína p47-phox (NCF-1) estão presentes em 30 por cento dos casos de doença granulomatosa crônica. Essa forma da doença é de herança autossômica recessiva e resulta em fenótipo de evolução mais benigno e início tardio em relação à forma ligada ao X, que corresponde a 56 por cento dos casos. DESCRIÇAO: Caso 1 - paciente feminina, iniciou infecções de repetição aos 10 anos, com impetigo, seguido de pneumonia grave 6 meses após. A gravidade da infecção pulmonar associada a abscesso hepático e sua refratariedade ao tratamento demandaram investigação laboratorial para imunodeficiência, com teste do nitroblue tetrazolium e dosagem de ânion superóxido compatíveis com doença granulomatosa crônica. A avaliação dos familiares confirmou o mesmo diagnóstico em seu irmão (Caso 2), que também iniciou infecções de repetição com impetigo aos 10 anos e pneumonia 6 meses após, porém tratada com sucesso ambulatorialmente. A análise de polimorfismo conformacional de cadeia simples revelou alteração da mobilidade eletroforética do éxon 2 do gene NCF-1. Identificou-se uma deleção dos nucleotídeos GT no éxon 2 por seqüenciamento do DNA. COMENTARIOS: Este estudo mostra a importância da avaliação de familiares, mesmo quando não apresentam história clínica típica de doença granulomatosa crônica. A identificação da mutação e sua correlação com o fenótipo dos pacientes é importante para estabelecer o prognóstico e o aconselhamento genético.

Surfactant protein-A levels in patients with acute respiratory distress syndrome.

BACKGROUND & OBJECTIVES: The decrease in surfactant protein-A (SP-A level) has recently been implicated in the pathophysiology of acute respiratory distress syndrome (ARDS). Mechanical ventilation is the main modality of treatment of ARDS. But information on the SP-A levels after mechanical ventilation is scanty. We therefore studied the effect of mechanical ventilation on SP-A levels in patients with ARDS. METHODS: In a prospective, observational study conducted in the Respiratory Intensive Care Unit of a tertiary care hospital in north India, 13 patients with ARDS requiring mechanical ventilation were included. SP-A levels in the bronchial aspirates were serially estimated by ELISA at the start of mechanical ventilation and after 24 and after 48 h. RESULTS: The SP-A level at the start of mechanical ventilation was 3.06 +/- 2.56 microg/ml. The levels gradually increased to 3.99 +/- 2.39 and 6.64 +/- 2.72 microg/ml, at 24 and 48 h respectively, and this increase was statistically significant (P < 0.05). Patients having an infectious etiology had lower SP-A levels compared to those with non-infections causes. Neither the initial SP-A level nor the increase in SP-A level correlated with the improvement in lung function or duration of ventilation. INTERPRETAION & CONCLUSION: The present study showed a progressive increase in the SP-A levels in patients with ARDS on mechanical ventilation. Further studies are required to confirm that the increase in SP-A levels may be one of the contributors for recovery in ARDS.