ObjectiveTo understand the detections of influenza A (H1N1) in 2009,and haemagglutinin (HA) gene mutations and the comparisons with standard strains.MethodsThe nasopharyngeal swabs from patients with influenza-like illness (ILI) in National Influenza Sentinel Surveillance Hospital and the outbreak epidemic area were collected.The virus typing and A (H1N1) viruses were tested by real time-polymerase chain reaction (RT-PCR).Then the pathogens were isolated with MDCK cells,the virus titer was determined with hemagglutination test and the virus typing was identified with hemagglutination inhibition test (HA1).The RT-PCR products of HA1 gene of virulent strains were sequenced and then analyzed through bioinformatics.Results A total of 996 pharyngeal swab specimens were tested,and nucleic acid positive cases included 337 A (H1N1) subtype,1 seasonal A (H1N1) subtype,67 A (H3N2) subtype,and 12 B type.The positive rate of nucleic acid detection of influenza was 41.87％ and that of A (H1N1) was 33.84％.Thirty-six influenza A (H1N1) virus strains were isolated,and 10 of them were successfully sequenced and several amino acid mutations were identified.There were 6 amino acid mutations found compared with vaccine strain A/California/07/2009 (H1N1),and 1 site was in area B of epitope.Conclusions A (H1N1) is absolute predominant among isolated strains in 2009.HA gene of virulent strains is mutated compared with vaccine strain provided by World Health Organization,which shows that the area B of epitope changes,while the key amino acid position 222 doesn't change.

Objective To analyze the differentially expressed genes in peripheral blood of human immunodeficiency(HIV)/tubercle bacilli co-infected patients and explore the biological regulatory mechanism and network of key proteins,so as to provide new evidence for early diagnosis and clinical treatment of HIV/TB co-infected patients. Methods Microarray gene chip data of HIV/TB co-infected patients were downloaded from public databases GEO and imported into the analysis software GEO,STRING,PANTHER,and GenClip. The gene expression profiles,protein interaction networks,processes of molecular biology,and gene functions were analyzed. Results The expression profiles of 15 529 genes between the two groups of patients were similar,and gene expression profiles from 44 subjects were highly correlated. The 251 differentially expressed genes had good diagnostic capabilities in the differential diagnosis of HIV/TB infection. RPLP1 might be a key gene in the diagnosis of HIV/TB infection. The differentially expressed genes and positive regulators showed certain functions such as external stimuli,signal transduction pathways in cells,migration of neutrophils,and immunological and other relevant functionalities. Meanwhile,they may also be involved in free radical-related apoptosis,inflammation,and activation pathways. Conclusions A total of 251 differentially expressed genes are found to be able to distinguish simple HIV infection from HIV/TB infection. Protein-protein interaction network of top 40 differential expression genes includes RPLP1 gene,which is possibly associated with HIV/TB co-infection and may be involved in and the positive regulation of external stimuli,signal transduction pathways in cells,migration of neutrophils,and immunological functions. These findings may provide certain evidence for the diagnosis and treatment of HIV/TB infection.

Objective To conduct bioinformatics analysis of children with severe malaria to find out the key gene changes in order to provide a new basis for the prevention and treatment of malignant malaria.Methods Microarray gene chip data was downloaded from public databases GEO and imported into the analysis software STRING,PANTHER and GenClip.The gene expression profiles,protein interaction networks,the process of molecular biology,gene function were analyzed.Results 623(1.93 ％) differentially expressed genes had a good diagnostic capabilities in the diagnosis of mild and severe malaria.OAS2,OAS3,IFIT3 and USP18 were the core sub-network node of the Protein-Protein Interactions.Differentially expressed genes mainly involved in the body's immune defense,immune response,response to external stimuli,the biological function of type 1 interferon activation pathways.Conclusion The progress of malaria of children may be in the regulation of OAS2,OAS3,IFIT3,USP18 and children's immune defense capacity decreased,the malaria began to progress more easily.

Objective To analyze the data of influenza A(H1N1) viruses surveillance and genetic characteristics from Taian City during 2005-2008,so a scientific basis can be provided for the prevention and treatment of influenza.Methods The specimens from Influenza-Like Illness(ILI) were collected.The viruses were isolated with MDCK cell and identified with HAI and RT-PCR.The product of PCR were sequenced.Then the sequences were analyzed through biometric software.Results A total of 121 influenza strains were obtained from 615 specimens,and 4 of them were identified as A(H1N1) subtype.There were 3 strains mutated on several sites.Compared with strains isolated in 2005,there were 5 and 8 mutations in the amino acid sequences of virus strains isolated in 2007 and 2008 respectively.And there were a total of 22 amino acid mutations compared with A/Brisbane/59/2007(H1N1).Conclusions Influenza type A(H1N1) are detected in Taian City.There are several mutations in the amino acid sequences of virus strains isolated in Taian. The antigenic drift of virus strains is due to accumulation of amino acid substitutions

Objective: To explore the influence of heat and noise exposure on the risk of hypertension in workers,and to provide evidence for prevention of hypertension in occupational population. Methods: Cluster sampling method was used to recruit 2 130 steel workers from four factories（north iron-making,long steel,cold steel and power department）of some steel company. A cross-sectional study was conducted to collect physical examination results,heat and noise exposure. Logistic regression models were used to analyze the effects of noise,heat and their interaction on hypertension. Results: Totally 1 971 valid questionnaires were collected,and the response rate was 92.54%. There were 654 workers suffering from hypertension,with a prevalence rate of 33.18%. There were 1 006 workers exposed to noise,accounting for 51.04%;and 853 workers exposed to heat,accounting for 43.28%. The prevalence rates of hypertension in workers exposed to noise and heat were higher than those in workers without the above exposure（P<0.05）. The prevalence rates of hypertension increased with the increase of age and working years（P<0.05）. The results of multivariate logistic regression analysis showed that noise（OR=1.711,95%CI：1.380-2.121）,heat（OR=1.721,95%CI：1.394-2.125）were risk factors for hypertension;the interaction between noise and heat on hypertension was not statistically significant（P>0.05）,while the interaction between noise and age（OR=1.086,95%CI：1.057-1.115）,between heat and age（OR=1.087,95%CI：1.059-1.115）both increased the risk of hypertension. Conclusion Occupational exposure to heat and noise are risk factors for hypertension. These two occupational hazards also interact with age,which can increase the risk of hypertension in workers.

Objective:To investigate the relationship between glutathione peroxidases (GPXs) gene expression in colorectal cancer tissues and survival prognosis, and to construct and evaluate a nomogram prediction model of GPXs for survival prognosis of colorectal cancer patients.Methods:The GPXs gene expresion data and other clinical data of 620 patients with colorectal cancer (455 cases of colon cancer and 165 cases of rectal cancer) were downloaded from The Cancer Genome Atlas (TCGA) database, and the GPXs gene expression data of 820 normal people were downloaded as controls, preprocessed by R language, and the gene expression data were analyzed for differential expression. Spearman rank correlation was used to analyze the correlation between GPXs gene expression and tumor mutation burden (TMB) in colorectal cancer tissues. Cox risk regression model was used to analyze the influencing factors of survival and prognosis of colorectal cancer patients. Nomogram models were constructed to predict overall survival (OS) of colon cancer and rectal cancer patients, and its predictive performance was evaluated by calibration curve.Results:In the GPXs family, there were statistically significant differences in the mRNA expressions of GPX1, GPX2, GPX3, GPX4, GPX5, GPX7 and GPX8 between colon cancer patients and normal population, and the mRNA expressions of GPX1, GPX2, GPX4 and GPX8 in colon cancer patients were higher than those in normal population (all P<0.05) . There were statistically significant differences in the mRNA expressions of GPX1, GPX2, GPX3, GPX4, GPX7 and GPX8 between rectal cancer patients and normal population, and the mRNA expressions of GPX1, GPX2, GPX4, GPX7 and GPX8 in rectal cancer patients were higher than those in normal population (all P<0.05) . Spearman rank correlation analysis showed that GPX2 ( r s=-0.27, P<0.001) and GPX7 ( r s=-0.11, P=0.043) expressions were negatively correlated with TMB in colon cancer. There were no significant correlations between GPXs genes expressions and TMB in rectal cancer tissues (all P>0.05) . In colon cancer, univariate analysis showed that GPX3 ( HR=1.22, 95% CI: 1.05-1.43, P=0.012) , GPX4 ( HR=1.39, 95% CI: 1.01-1.92, P=0.045) , age ( HR=1.02, 95% CI: 1.01-1.04, P=0.010) and pTNM-stage ( HR=1.78, 95% CI: 1.43-2.21, P<0.001) were the influencing factors of OS. Multivariate analysis showed that GPX4 ( HR=1.96, 95% CI: 1.09-3.51, P=0.024) , age ( HR=1.02, 95% CI: 1.00-1.04, P=0.042) and pTNM-stage ( HR=1.61, 95% CI: 1.21-2.15, P=0.001) were the independent risk factors of OS. In rectal cancer, univariate analysis showed that age ( HR=1.08, 95% CI: 1.04-1.13, P<0.001) was the influencing factor of OS. Multivariate analysis showed that GPX7 ( HR=0.44, 95% CI: 0.22-0.88, P=0.020) , GPX8 ( HR=3.17, 95% CI: 1.63-6.17, P=0.001) and age ( HR=1.10, 95% CI: 1.04-1.16, P=0.001) were the independent influencing factors of OS. The consistency index (C-index) of the nomogram model for predicting OS in patients with colon cancer and rectal cancer were 0.71 (95% CI: 0.63-0.79) and 0.88 (95% CI: 0.82-0.94) respectively. The calibration curve showed that the prediction curve of the two models had a good fit with the real curve. Conclusion:GPX4 is an independent risk factor affecting the prognosis of colon cancer patients. Patients with high GPX4 expression have a poor prognosis. GPX7 and GPX8 are independent prognostic factors for rectal cancer patients, and the rectal cancer patients with low GPX7 expression and high GPX8 expression have poor prognosis. The nomogram constructed based on the above factors can better predict the prognosis of patients with colon cancer and rectal cancer.

To explore the mechanisms for Type 2 diabetes mellitus (T2DM) in children and provide genomic evidence for its early diagnosis and treatment.
 Methods: The peripheral blood gene chip datasets from 12 children with T2DM and 24 healthy children were retrieved from the Gene Expression Omnibus (GEO) at National Center for Biotechnology Information (NCBI). The differentially expressed genes were screened by R language software. GenCLiP 2.0, STRING, and Cytoscape software were used to analyze the biological functions, protein-protein interaction network, signal pathway, gene-pathway network, expression of key genes, and predictive value between the two differentially expressed genes.
 Results: A total of 79 differentially expressed genes were identified. Among them, 58 (73.42%) were up-regulated, and 21 (26.58%) were down-regulated. Differentially expressed genes mainly involved molecular functions and biological processes, such as defensive response, response to external stimulus, and inflammatory responses. At the same time, they were mainly involved in the Leishmaniasis, cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway. interleukin 1β (IL-1β), jun proto-oncogene (JUN), and IL-8 were 3 important linking nodes in the protein-protein interaction network. JUN and IL-1β were key genes, which were related to interleukin 17 (1L-17) signaling pathway, Toll-like receptor signaling pathway and so on. The expression of JUN gene in peripheral blood of children with T2DM was decreased while the expression of IL-1β gene was increased. JUN and IL-1β genes possessed certain diagnostic and predictive value in children with T2DM.
 Conclusion: The gene expression profile of peripheral blood in children with T2DM changes significantly. The genes of JUN and IL-1β are closely related to T2DM in children. IL-1β gene expression level shows a better predictive value on T2DM in children.
Child ; Diabetes Mellitus, Type 2 ; diagnosis ; genetics ; therapy ; Down-Regulation ; Gene Expression Profiling ; Humans ; Interleukin-1beta ; genetics ; Oligonucleotide Array Sequence Analysis ; Proto-Oncogene Proteins c-jun ; genetics ; Signal Transduction ; genetics ; Software ; Transcriptome ; Up-Regulation

【Objective】 Based on the high-throughput sequencing data of the whole genome， genomics and bioinformatics analyses were made to analyze the gene expression changes in the epithelial cells of the lung tissue from patients with coronavirus disease 2019 （COVID-19）， and explore the effects of the new coronavirus SARS-CoV-2 on human lungs. This study can provide a theoretical basis for the exploration of SARS-CoV-2 on the pathogenesis of lung tissue. 【Methods】 The public data set GSE160435 was retrieved. The data were analyzed by Network analyst， Cytoscape 3.7.2， String 11.0， and other software. The differentially expressed genes were screened， gene function （Gene Ontology， GO） and signal pathway KEGG （Kyoto Encyclopedia of Genes and Genomes） enrichment analysis were carried out. We established the Protein-protein Interactions Network （PPI）， PPI of lung tissue-specific DEGs， DEG microRNA regulatory network， Transcription Factor （TF）-DEG regulatory network， and environmental chemicals DEGs regulatory network. 【Results】 We found 324 DEGs in the lung epithelial cells of patients with COVID-19， of which 112 （34.57%） were upregulated and 212 （65.43%） were downregulated. Enrichment analysis showed that DEGs were mainly involved in biological processes such as virus-related defense response， mainly involved in protein digestion and absorption， anti-human papillomavirus infection and other signaling pathways. Specific PPI network closely related to DEGs and lung tissue showed that PDGFRB and KIT were core proteins； hsa-mir-340 had targeted interaction with DEGs. It indicated that HOXB4， ISG15 and other related genes were regulated by transcription factors； DEGs interacted with environmental chemicals such as nickel and estradiol. 【Conclusion】 The gene expression pattern of lung epithelial cells in lung tissue of COVID-19 patients has changed significantly. Proteins or genes such as PDGFRB， MMP9 and KIT may play a vital role in the defense immunity of lung tissue. Micro-RNA， TF， signaling pathway molecules， environmental chemicals， and lung tissue-specific genes also play a role in the above-mentioned process. This study provides new ideas for exploring the pathogenic mechanism of SARS-CoV-2 on lung tissue and formulating clinical prevention， diagnosis and treatment measures.

Objective To investigate the changes of sex hormone and androgen receptor levels and evaluate the relationship of the sex hormones and androgen receptor with coronary heart disease (CHD) in elderly men. Methods A cross-sectional study was performed in 539 elderly men, including 400 healthy people aged 62-92 years and 139 CHD patients aged 60-88 years. The plasma concentrations of total testosterone (TT), free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), estradiol (E2), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured. The androgen receptor (AR) level was tested by flow cytometry. Results The fluorescence intensity of DHEAS, TT, SHBG, FT and AR were significantly lower in CHD group than in healthy group (P<0.01);however, FSH and E2 in CHD group were higher(P(0.01). Age was negatively correlated with TT(r=-0.28,P<0.01) and FT (r=-0.17,P<0.05), and positively correlated with SHBG(r=0.14,P<0.05) and E2 (r=0.33, P<0.01). AR fluorescence intensity was negatively correlated with systolic blood pressure (r=-0.12,P<0.01). Logistic regression analysis indicated that TT (OR=1.065,9% CI: 1.012～1.121,P<0.05), SHBG(OR=0.994,95% CI:0.990～0.998,P<0.01) and AR (OR=0.971,95%CI:0.956～0.986, P<0.01)were significantly associated with CHD in elderly male patients. Conclusions The levels of DHEAS, TT, SHBG, FT and AR are lower in elderly men with CHD than in elderly healthy men;however, the FSH and E2 concentrations are higher. Low levels of TT, SHBG and AR may be the independent risk factors for CHD in elderly men.

Objective Although aspirin resistance has been recognized to occur in patients with diabetes mellitus, the prevalence and related risk factors for aspirin resistance in elderly patients with diabetes mellitus have not been reported yet. The purpose of the present study was to evaluate the prevalence and potential risk factors for aspirin resistance in elderly patients with type 2 diabetes.Methods The 140 elderly patients [aged from 60 to 92 years, mean age (73.8±8. 0) years] with type 2 diabetes receiving daily aspirin therapy (≥ 75 mg) over one month were recruited. Platelet aggregation was measured by light transmittance aggregometry (LTA) and thrombelastograph (TEG)platelet mapping assay. Results By LTA, 6 patients (4.3%) of the diabetic patients were found to be resistant to aspirin therapy, 44 patients (31.4 %) were semi-responders. By TEG, 31 patients (22. 1%) were aspirin resistant. Among the 31 patients who were aspirin resistant by TEG, 3 were aspirin resistant by LTA. In the multivariate logistic regression analysis, female gender (OR= 5. 54,95%CI: 1.17-27.47, P=0.036) and homocysteine level (OR=1.15, 95%CI: 1.00-1.35, P=0. 043) were statistically significant risk factors for aspirin resistance by TEG. Conclusions The prevalence of aspirin resistance in elderly patients with type 2 diabetes is considerably higher in elderly female patients and in elderly patients with higher serum homocysteine level.