Clinical features and risk factors of severe influenza virus A pneumonia in children in Children's Hospital of Chongqing Medical University / 中国实用儿科杂志

OBJECTIVE: To analyze the clinical features and risk factors of severe influenza virus A(IVA)pneumonia in children. METHODS: Clinical data of 617 children diagnosed with influenza virus A pneumonia who were hospitalized in Children's Hospital of Chongqing Medical University from January 2014 to March 2018 were analyzed retrospectively. Of these children there were 144 cases of severe IVA pneumonia. Logistic regression analysis was used to analyze the risk factors of severe IVA pneumonia. RESULTS: The prevalence of pneumonia associated with IVA in children was seasonal in Chongqing.The peak of IVA-associated pneumonia in 2017 was from March to May,August to October, and December to February of the following year. About 74% of patients were younger than 3 years and boy accounted for 64.1%. Among them,201(32.6%)children had underlying diseases,which were mainly malnutrition,congenital heart disease,congenital airway dysplasia and asthma. Fever and cough were the main clinical manifestations,and some were combined with gastrointestinal symptoms.Among the 617 cases,51.2% were positive for bacteria,13.9% were positive for virus other than IVA,and 12.2% were positive for Mycoplasma pneumoniae. Severe pneumonia cases progressed rapidly,and 127 children of the 144 children with severe IVA pneumonia had respiratory failure,acute respiratory distress syndrome,cardiac insufficiency and toxic encephalopathy within 3-5 days after illness onset. The multivariate analysis found that congenital heart disease(OR3.98,95%CI 2.31-6.86),nervous system disease(OR 3.33,95%CI 1.42-7.80)and malnutrition(OR 2.21,95%CI 1.29-3.79)were independent risk factors of severe pneumonia associated with IVA. CONCLUSION: Pneumonia associated with IVA in children is prevalent in winter and spring,with some summer epidemic peaks in Chongqing. Congenital heart disease,nervous system disease and malnutrition are independent risk factors for severe pneumonia associated with IVA.

Action mechanism of Mahuang Xixin Fuzi decoction for mice with influenza based on metabolomics information / 中国中药杂志

This study aimed to analyze the endogenous metabolite changes in the serum of mice infected with H1N1 virus after intervention by Mahuang-Xixin-Fuzi decoction (MXF) based on metabolomics method, investigate potential biomarkers and related metabolic pathways, and explore the therapeutic mechanism of MXF through metabolomics technology. Thirty-six Kunming (KM) mice were randomly divided into three groups: normal group, model group and MXF group. Influenza virus H1N1 was used by nasal drip to establish influenza mice model. The mice in MXF group were orally administrated with MXF for 6 consecutive days after inoculation, and the other two groups were given with equal volume of saline solution in the same way. Body weight, rectal temperature, morbidity and mortality were recorded daily. Serum samples were collected 24 hours after the last administration for HPLC-TOF-MS analysis. The results showed that as compared with the normal group, the body weight and rectal temperature were decreased in model group, and their lung index and mortality rate were significantly increased (P<0.05); MXF had good therapeutic effects on the abnormity of body weight, rectal temperature, lung index and high mortality rate of mice infected with H1N1 virus. The original data collected from the serum samples were analyzed with R language, MPP, SIMCA-P and other software, and significant changes were found in 14 kinds of endogenous substances from mice serum (P<0.05). As compared with model group, the potential metabolic markers in MXF group recovered to normal levels to a certain degree after being intervened by MXF. Further analysis with MetPA data platform showed that, the pathways involved in 14 metabolites included glucose metabolism, arachidonic acid metabolism, glycerophospholipids and sphingolipids metabolism etc. The metabolomics study and pharmacological experiment showed that MXF might play a role of efficacy by improving glucose metabolism, regulating arachidonic acid metabolism, glycerophospholipid and sphingolipid metabolic pathways.

Mechanism of Pharmacological or Toxicity Effect of Ribavirin on Kidney-Yang Deficiency Syndrome Mice Model Infected with Influenza Virus A Based on Serum Metabolomics / 中国药学杂志

OBJECTIVE: To analyze the endogenous metabolite changes in the sera of kidney-yang deficiency syndrome mice infected with influenza virus A after intervention by ribavirin. And to explore the mechanism of pharmacological or toxicity effect of ribavirin. METHODS: KM mice were randomly divided into three groups as normal group, model group and ribavirin group. Mice were infected with virus A after fifteen days Kidney-Yang deficiency syndrome was established. Ribavirin group were orally administrated with ribavirin for 6 consecutive days after inoculation, and the other two groups were given with equal volume of saline solution in the same way. Body weight, rectal temperature were recorded daily. Serum samples were collected from mouse 24 h after the last administration for HPLC-TOF/MS analysis. RESULTS: The results show that ribavirin has good therapeutic effects on the lung index and high mortality rate of mice model. Compared with normal and model groups, the body weight and rectal temperature of them performed falling continuously. The LC-MS data were analyzed with multivariate statistical analysis and 14 potential metabolic markers were obtained which contained D-glucose, sphinganine, linoleic acid and so on. In ribavirin group, metabolism of linoleic acid, arachidonic acid and sphinganine appeared the trend of normal. And sugar and glycerophospholipid became disorders. CONCLUSION: The metabolomics study and pharmacological experiment show that ribavirin might play a role of efficacy in a way that has close correlation with the linoleic acid, arachidonic acid and sphingolipid metabolic pathways. And the toxicity effect may be related to sugar and glycerophospholipid metabolic pathways.

Prediction of antigenic epitopes on HA, NA amino acid sequences of novel influenza A (H7N9) virus and analysis association between susceptibility and HLA-Ⅱalleles / 中国免疫学杂志

Objective:To compare the amino acid sequences difference of HA,NA novel influenza virus A/H7N9 isolates, decipher possible B cell epitopes and T cell epitopes of HA,NA protein,and analyze the association between susceptibility and HLA polymorphisms.Methods:The amino acid sequences of novel influenza A ( H7N9) virus were downloaded from Genbank.Phylogenetic trees were constructed based on the amino acid sequences of HA and NA by using software Clustal X and MEGA 4.0.B cell and T cell epitopes were respectively predicted with Protean software and NetMHCⅡ2.2 Server online server.Results:The homology of HA and NA proteins of H7N9 virus was high.10 B cell epitopes and 15 T cell epitopes were randomly distributed throughout HA sequence and 12 B cell epitopes and 9 T cell epitopes were randomly distributed throughout NA sequence.HLA-DRB1*0701 allele which was commonly observed in Northern Chinese population have a high binding affinity for 9-mer peptides of HA and NA proteins.Conclusion:The prediction of B and T cell epitopes of HA and NA proteins with multiple methods benefits the research and development of vaccine against human infection with avian influenza A H7N9 virus.HLA-DRB1*0701 allele may contribute to susceptibility to novel influenza A (H7N9) virus.H7N9 influenza virus is more easily spread in Urumqi,Harbin,Shandong Province,Liaoning Province,Beijing, Shijiazhuang and Tianjin of China.

Influenza humana: revisão sobre doenças emergentes e a saúde do trabalhador de enfermagem / Influenza humana: revisión acerca de enfermedades emergentes y la salud del trabajador de enfermería / Human influenza: review on emergent diseases and the nursing worker’s health

As doenças emergentes têm sido consideradas uma grande ameaça mundial, e as síndromes respiratórias emergentes agudas podem representar riscos importantes para os trabalhadores de saúde, em geral, e de enfermagem, em especial nas situações de epidemia. Objetivou-se revisar a bibliografia recente em termos de artigos científicos e informes técnicos sobre a Influenza Humana e seus tipos e sua relação com a saúde do trabalhador de enfermagem. Foram consultadas bases de dados de periódicos na Internet, bem como de agências de cooperação internacional em saúde e de notícias, selecionando-se para discussão 10 artigos e cinco informes técnicos. Os resultados evidenciam que a exposição a risco biológico por parte dos trabalhadores de enfermagem tem sido significativa. Na conclusão, debate-se a questão das doenças emergentes e seu impacto na saúde dos trabalhadores de saúde, bem como questões relativas a algumas determinações macroestruturais das mesmas.

Emerging diseases have been regarded as a worldwide threat, and emerging acute respiratory syndromes can offer high risk to health workers, in general and to nurses, in particular, in epidemic situations. A bibliographic review on recent scientific papers and technical reports on human influenza and subtypes is presented, as well as its relation to nurses’ health. Scientific agencies, news agencies, and international cooperation agencies’ databases were consulted. Ten papers and five reports were selected for discussion. Results focus on the impact of emerging diseases on health workers as well as some of their macro structural determinants.

Las enfermedades emergentes son consideradas uma gran amenaza a la salud mundial, y las síndromes emergentes agudas respiratórias pueden presentarse como um severo riesgo a la salud del trabajador de salud y de enfermería. Se objetivó hacer una revisión de la bibliografia reciente en términos de artículos científicos y reportes técnicos acerca de la Influenza Humana y sus subtipos y su relación con la salud de trabajador de enfermería. Las bases de datos cientificas, de agencias de cooperación internacional en salud y de agencias de noticias fueran acesadas, seleccionándose 10 articulos y cinco informes para discussión. Los resultados muestran que el riesgo biológico para los trabajadores en enfermería es considerado significiativo. En las conclusiones, las enfermedades emergentes y su relación con la salud laboral es discutida, así como algunas de sus determinaciones macroestructurales.

The Influence of Influenza Virus A on Alveolar Fluid Clearance in Rat Lungs / 中国医科大学学报

Objective To investigate the influence of influenza virus A（H1N1,A/PR/8/34 strain）on alveolar fluid clearance（AFC）in vivo and the effects of β1-adrenergic agonist on AFC in rat lungs infected by H1N1.Methods Fortyfive rats were divided into control group（n =12）,H1N1 infection group（the rats were infected with influenza virus strain A/PR/8/34,n =18）,β1-adrenergic agonist groups（the rats were administrated with β1-adrenergic agonist after HIN1 infection,n =15）.AFC was estimated by the progressive increase in the albumin concentration over 30 minutes.The activity of cAMP and cGMP in the lung tissues of control,H1N1 infection and β1-adrenergic agonist groups was measured.Results The infection with H1N1 resulted in a decline in AFC 9.15±1.01% vs control group 17.25±1.01% and increased lung water content（W/D was 6.77±0.13 vs control group 4.99±0.02）.H1N1-mediated inhibition of AFC could be reversed to 14.41±1.41% by the administration of β1-adrenergic agonist denopamine.H1N1 infection increased cGMP levels 7.34±0.40 pmol·mg-1· mg-1 vs control group 5.10±1.88 pmol·mg-1·mg-1 and decreased cAMP levels 1.43±0.06 nmol·mg-1·mg-1 in lung tissues compared with control group.β1-agonist denopamine reversed the level of cAMP to 2.06±0.16 nmol·mg-1·mg-1 and cGMP to 6.16±1.36 pmol·mg-1·mg-1.Conclusion H1N1 infection decreased AFC and increased lung edema.β1-agonist denopamine could reverse AFC and the ratio of cAMP/cGMP in H1N1 infected lung tissues.β1-agonist might regulate AFC through the pathway of cAMP-PKA.

Traceability of the A/H3N2 virus borne influenza pandemic in Zhejiang province,1998 / 中华流行病学杂志

Objective To trace back to the influenza pandemic caused by A/H3N2 virus happened in Zhejiang province,1998.Methods The whole genome of three isolates related to Zhejiang influenza virus was amplified through RT-PCR,and the identified sequences were aligned with the sequences downloaded from GenBank of the H3N2 strains which were circulating in other regions during 1995 to 1998.The crossing HAI titers of the reference strains were measured by HAI test and antigenic ratios were calculated.Results The Phylogenetic tree,constructed based on HA sequence showed that the dominant strains A/Zhejiang/11/98 and A/Zhejiang/18/98 were significant different from the isolates circulated in other regions during 1995 to 1996 and the strains isolated in the mainland of China,in 1997.Although the A/Zhejiang/11/98 and A/Zhejiang/18/98 strains were distributed in the same cluster with A/Sydney/5/97,the two strains were closer to the epidemic strains isolated in Hong Kong and New York in the later part of 1997.Based on HAI,NA and MP genes,A/Zhejiang/18/98 seemed to be the closest one to the Hong Kong epidemic strains,and the genetic distances between A/Zhejiang/18/98 and New York strains were shorter than that with A/Sydney/5/97 based on PA,HA and NS genes.There were only 1-3 amino acid differences between A/Zhejiang/18/98 and Hong Kong or New York strains,whereas 7 amino acid differences with A/Sydney/5/97,in which three were located in the antigenic determinant regions.Data from the crossing HAI test showed that the antigenic ratio between A/Zhejiang/18/98 and A/Sydney/5/97 had reached 2.0,indicating the antigenic difference to a certain extent.Additionally,the onset of the influenza epidemic during 1997 to 1998 also suggested the possible route of transmission related to this H3N2 virus.Conclusion The influenza pandemic occurred in Zhejiang province in 1998 was possibly caused by the importation of a newly identified H3N2 influenza variant via Hong Kong and New York in late 1997.

Pneumonia por Influenza A(H1N1) em paciente imunossuprimido após transplante cardíaco / Influenza A (H1N1) pneumonia in an immunossupressed patient after heart transplantation / Neumonía por Influenza A (H1N1) en paciente inmunosuprimido tras transplante cardiaco

O papel da resposta imunológica durante a infecção pelo vírus Influenza H1N1 não está totalmente estabelecido, mas acredita-se que atue de forma decisiva no agravamento do quadro e no aparecimento da síndrome de desconforto respiratório agudo. O papel de terapias imunomoduladoras no controle de infecções virais também não é consensual e faltam dados de literatura para se definir as indicações de seu uso. Neste relato de caso, apresentamos, segundo nosso conhecimento, pela primeira vez, o relato de um paciente transplantado cardíaco que apresentou infecção pelo vírus H1N1 e evoluiu de forma favorável, trazendo um questionamento sobre o real papel da terapia imunossupressora como fator de risco para a forma grave da doença.

The role of the immune response during Influenza H1N1 virus infection is not yet fully established, but it is believed that it decisively participates in the severity of the disease as well as in the development of acute respiratory distress syndrome. The role of immunomodulating therapies in the control of viral infections is not a consensus either, and data from the literature defining the indications for their use are lacking. The present report is, to our knowledge, the first on a heart transplant patient who developed H1N1 virus infection and had a favorable outcome, thus generating discussion on the real role of immunosuppressive therapy as a risk factor for the severe form of the disease.

El rol de la respuesta inmunológica durante la infección por el virus Influenza H1N1 no está totalmente establecido, sino que se cree que él actúe de forma decisiva en el agravamiento del cuadro y en el surgimiento del síndrome de distrés respiratorio agudo. El papel de terapias inmunomoduladoras en el control de infecciones virales también no es consensual y nos faltan datos de la literatura para definirse las indicaciones de su utilización. En este caso clínico presentamos, según nuestro conocimiento, por primera vez, el relato de un paciente transplantado cardiaco que presentó infección por el virus H1N1 y evolucionó de forma favorable, y aprovechamos para poner en cuestión el real papel de la terapia inmunosupresora como factor de riesgo para la forma severa de la enfermedad.

Application of the rapid influenza testing during 2007-2008 flu season in Beijing city / 中华检验医学杂志

Objective To analyze the application value of the rapid testing for influenza during 2007-2008 flu season at fever clinic in Beijing Chaoyang hospital Methods 500 patients with diagnosis of influenza-like illness were prospectively enrolled. Pharyngeal swabs were collected for influenza viral culture and rapid testing for influenza. Demographic characteristics, age, symptoms, lab tests, symptom recovery time and medical expense were also collected. The sensitivity, specificity, positive predictive value and negative predictive value for rapid testing were analyzed. Results A total of 500 patients were enrolled between Dec 2007 and March 2008. Among them 498 cases were used for analysis. Influenza B was most common by virus culture methed(n=208,41.8%) ,followed by influenza A (n=51,10.2%). The average age was 35, and the ratio of male to female was 1.47:1. Compared with the group of positive culture, patients with influenza were more likely to get cough, sore throat, and nasal congestion (t=13.728, 4.014and 4.720,P<0.001 or 0.05, respectively). A total of 260 cases were subjected to rapid testing, Among them 18 cases were influenza A positive and 132 cases were influenza B positive. The rapid testing had a sensitivity of 77.1 % and a specificity of 70.1%. The positive predictive value was 78.6% and the negative predictive value was 68.2%. The rapid testing had enhanced the proportion of anti-viral treatment from 0 to 26% and reduced the proportion of antibiotic use from 63.4% to 20. 7%. Conclusions Influenza B is the most predominant pathogen during 2007-2008 flu season among patients with influenza-like illness in Beijing. The rapid testing with high sensitivity and specificity provides guidance on clinical practice.

Origins and Views of The 2009 A/H1N1 Influenza Pandemic / 生物化学与生物物理进展

The pandemic outbreak of influenza has been started from Mexico in 2009 to 70 countries during 2 months. On 11th of June , WHO announced influenza pandemic alert level rose to the highest level 6, which means the first influenza pandemic in 21st century is coming. Till 6th of July, 94 512 confirmed cases from more than 120 countries and areas were reported, including 429 cases were died. The genetic fragment of swine, poultry sources and human influenza viruses are contained in this strain, A/H1N1 influenza virus, of the pandemic. It is of great significance of studying the genetic reassortment, evolution and its biological characteristics of this virus strain to prevent and control the pandemic. At present, the genetic evolution of strain has been identified, and the potential biological characteristics have been analyzed by genetic traits, however, clinical manifestation should be further concerned, and the tendency of influenza pandemic and genetic changes need to be monitored closely. The complexity of influenza virus ecosystems, mutation of genome, and easy to preserve in "Nature Gene Pool" and reassortment, make the influenza pandemic inevitable. We should face the threat of influenza pandemic, enhance the surveillance of influenza virus in ecosystems, strengthen the epidemiological investigation, develop the vaccines and drugs, and establish an effective public health security system, in order to reduce the destruction of the influenza pandemic.

Preparation of immunoglobulin Y against avain influenza virus(H_5N_1)and studies on the inhibitory effect to influenza virus A (FM_1) in vitro / 中国免疫学杂志

Objective:To prepare the immunoglobulin Y(IgY) against Avain Influenza Virus (H5N1) and to investgate its inhibitory activity to Influenza virus A (FM1).Methods:Iimmunized by Avain Influenza vaccine,IgY against Avain Influenza Virus was purified from the yolk and then the antibody was enriched by the means:caprylate acid-two-step salt precipitation-gel chromatograph.TD0 of IgY and the inhibory effectiveness were showed by nhibiting cytopathic effect (CPE) thst in MDCK infected with Influenza virus A(FM1).Results:IgY against Avain Influenza Virus was obtained.The TD0 value of IgY against Avain Influenza to MDCK cell line was 1.764 mg/ml,while at the dosage as low as 0.082 8 mg/ml the lnfluenza virus A(FM1) was still inhibited in vitro.Connchusion:Caprylate acid-two-step salt precipitation-gel chromatograph can prepare IgY successfully and the inhibitory effectiveness of IgY is good for inhibition of Influenza virus A(FM1).

Clinical study on community-acquired adult respiratory tract infection of influenza virus A / 中国实用内科杂志

Objective To describe characteristics of adult respiratory tract influenza virus A (INFA)infection.Method 804 adult patients with acute respiratory tract infections were enrolled and 156 cases of healthy adults were concomitantly selected. Enzyme-linked immunoabsorbent assay was used to measure INFA serum specific IgM antibody.Result (1)In the total patients , 17.6% had positive INFA-IgM,significantly higher than the control(P

Monitoring of influenza by shell viral assay and direct immunofluorescent staining / 中华检验医学杂志

Objective To establish a rapid culture method for monitoring of influenza circulation and laboratory diagnosis of individual patients with influenza. Methods Nasal aspirate specimens were spun onto 24-well plate containing confluent monolayers of Madin-Darby Canine Kidney (MDCK) cells. Fluorescein labeled monoclonal antibodies to influenza A and B viruses were used to stain and type the isolates. Results A total of 713 nasal aspirates specimens from patients experiencing influenza-like symptoms was collected in Beijing between December of 2000 and March of 2001, 187(26 2%) specimens were found with influenza A virus and 109(15 3%) with influenza B virus. 2 2% with influenza A and 11 2% with influenza B virus were detected in 89 nasal aspirates specimens between Jan-Apr 2002. Conclusion Prevalence of influenza was low during 2000～2002 year non-epidemic period in Beijing. The combination of shell viral assay and direct immunofluorescent staining can provide a rapid laboratory diagnosis of influenza, which makes possible for the patients to receive treatment of anti-influenza virus drugs.

IL-11, IFN-gamma and ECP levels in nasopharyngeal secretions from non-asthmatic wheezing children with respiratory syncytial virus or influenza A virus infections / 천식및알레르기

BACKGROUND: Infection with respiratory virus has been shown to exacerbate asthma in humans. However, the role of a respiratory virus in the pathogenesis of chronic asthma and/or wheezing in young children has not been clearly defined. The objective of this study was to determine whether respiratory virus infections such as RSV, and influenza A virus are related to the productions of IL-11, IFN-gamma, and ECP levels in nasopharyngeal secretions. METHOD: We compared IL-11, IFN-gamma, and ECP levels in nasopharyngeal secretions from 38 non-asthmatic wheezing children with viral infections (RSV in 21 children, influenza A virus in 17 children), and 16 non-asthmatic healthy children who were included as the controls. IL-11, and IFN-gamma levels were analysed by ELISA. ECP concentrations were measured by monoclonal antibody-based fluorometric assay. RESULT: RSV infection in children induced a greater release of IL-11 in nasopharyngeal secretions than in influenza A virus infection, and in the controls. The release of IFN-gamma levels in nasopharyngeal secretions from children with influenza A virus infection was significantly higher than in nasopharyngeal secretions from children with RSV. ECP levels of subjects with viral infection were significantly higher than in control children. CONCLUSION: This study demonstrated that RSV is a potent inducer of IL-11 elaboration in nasal epithelium and that IL-11 is an important mediator in the pathogenesis of RSV infection. Increased IFN-gamma production in response to the influenza A virus infection may be related to effective Th1 responses.

Apoptosis of endometrial adenocarcinoma cell line JEC induced by influenza virus H_3N_2 / 第三军医大学学报

Objective To study the apoptosis-inducing effects and mechanisms of influenza virus A H_ 3 N_ 2 on a self-established endometrial adenocarcinoma cell line JEC. Methods JEC cells were infected with different concentrations of H_3N_2, the apoptosis were detected using the HE staining, DNA agarose gel electrophoresis and flow cytometry. The expressions of Fas, FasL and TGF-? were examined by immunocytochemical staining. Results After infection, the JEC cells showed the morphological apoptosis; DNA agarose electrophoresis demonstrated a ladder-like pattern of DNA fragments; FITC/PI stained FCM showed the apoptotic rate of JEC had been decreased along with the prolonging of infected time and elevated with the increase of the virus concentrations. Immunocytochemical staining showed that enhanced expression of Fas, attenuated expression of TGF-?, and no expression of FasL after H_3N_2 infection. Conclusion Influenza virus A H_3N_2 can induce JEC cells to apoptosis in time- and concentration- dependent manners, which may be related with the expressions of Fas and TGF-?.