Objective To predict and preliminarily validate potential shared key genes involved in cardiac complications caused by influenza A virus(IAV)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infections.Methods Differentially expressed genes(DEGs)associated with cardiac complications were obtained from the Gene Expression Omnibus(GEO)database.A hierarchical intersection strategy was applied.First,cardiac complication related DEGs were overlapped with 2 independent virus related gene sets:3 454 human genes linked to IAV infection in GeneCards and 333 human protein-coding genes interacting with SARS-CoV-2 in the Human Protein Atlas.The 2 overlap results were then intersected to yield 22 hub genes.Lasso regression,random forest(RF)and support vector machine algorithms(SVM)were employed to refine this list.Predicted genes were validated in vitro in H1N1-infected human cardiomyocyte AC16 cells and in vivo in IFITM3 knockout mice challenged with H1N1,assessing transcriptional changes.Results A total of 22 hub genes were identified through integrative bioinformatics analysis.Application of the 3 machine learning algorithms resulted in 5 common key genes:ACE2,TBK1,NUP210,PUSL1,and MEPCE.In vitro infection of AC16 cells with H1N1 revealed dynamic transcriptional changes in all 5 genes post-infection(P<0.05).In vivo experiments using H1N1-infected IFITM3 knockout mice confirmed the dynamic mRNA expression changes of these 5 genes,consistent with the in vitro results(P<0.05).Conclusion By combining multilayered bioinformatics analysis with 3 machine learning approaches,5 common key genes are identified:ACE2,TBK1,NUP210,PUSL1 and MEPCE.Validation in H1N1 infection models confirms their relevance to IAV-induced cardiac complications.

Objective:To investigate the correlation between the single nucleotide polymorphism (SNP) of the PLCE1 gene and children with primary nephrotic syndrome (PNS) in Guangxi Zhuang Autonomous Region. Methods:This study was a retrospective study, a case-control study was used to select 155 cases of PNS in Guangxi Zhuang children attending the Affiliated Hospital of Youjiang Medical University for Nationalities from January 2017 to January 2021 (PNS group), and 100 healthy Guangxi Zhuang children who were physically examined during the same period (healthy control group). Genotyping of PLCE1 SNP rs3765524, and rs2274223 were performed using the second-generation gene sequencing technology, and their correlation with the development of PNS was analyzed. Logistic regression analysis was used for correlation analysis, and Chi- square test or Fisher′ s exact probability method was used for comparison between groups. Results:(1)Compared with the healthy control group, PLCE1 rs3765524 was correlated with the risk of PNS in children of PNS group, and the TT genotype may reduce the risk of PNS in the co-dominant model ( OR=0.435, 95% CI: 0.238-0.794, P=0.007). There were no significant differences in the genotype of PLCE1 rs2274223 and the frequency of allele distribution between PNS group and healthy control group (all P>0.05). (2) A strong linkage disequilibrium existed at PLCE1 SNP rs3765524 and rs2274223.(3) There were no significant differences in the frequency of the distribution of haplotypes AC, AT and GT between PNS group and healthy control group (all P>0.05). Conclusions:PLCE1 SNP rs3765524 is correlated with the risk of PNS in children in Guangxi Zhuang Autonomous Region, and the TT genotype may be a protective factor for PNS in children in Guangxi Zhuang Autonomous Region.

Objective:To investigate the relationship between single nucleotide polymorphic (SNP) loci of PLCE1 gene and primary nephrotic syndrome (PNS) and its response to glucocorticoid therapy in Guangxi Zhuang children. Methods:It was a retrospective cohort study. One hundred and fifty-five Guangxi Zhuang children with PNS in the Affiliated Hospital of Youjiang Ethnic Medical College from October 2020 to May 2022, and 100 healthy Zhuang children during the same period as controls were included. Four SNP loci including rs17109674, rs10786156, rs3740360 and rs2274224 of PLCE1 gene were selected and high-throughput sequencing was used to analyze the genotypes. Logistic regression analysis model was used to analyze the correlation between each SNP locus and onset of PNS and steroid-resistant nephrotic syndrome. The SHEsis online software was used to analyze the link disequilibrium of each SNP locus, and construct the haploid type. Results:(1) Logistic regression analysis results showed that AC+CC genotype (AA as reference, OR=0.449, 95% CI 0.256-0.786, P=0.005), AC genotype (AA as reference, OR=0.354, 95% CI 0.188-0.667, P=0.001) and C allele gene (A as reference, OR=0.615, 95% CI 0.390-0.971, P=0.037) of rs3740360 were correlated with the risk of PNS in children. The genotypes and allele genes of rs17109674, rs10786156, rs3740360 and rs2274224 were not associated with the risk of steroid-resistant nephrotic syndrome in children (all P>0.05). (2) Strong linkage disequilibrium existed between rs10786156 and rs2274224 ( D'=0.702, r2=0.484). rs17109674 and rs10786156 ( D'=0.128, r2=0.007), rs17109674 and rs3740360 ( D'=0.142, r2=0.007), rs17109674 and rs2274224 ( D'=0.045, r2=0.001), rs10786156 and rs3740360 ( D'=0.255, r2=0.023), and rs3740360 and rs2274224 ( D'=0.281, r2=0.028) all had weak linkage disequilibrium. (3) The haploid AGCG ( OR=0.282, 95% CI 0.079-1.008, P=0.038), GGCC ( OR=0.327, 95% CI 0.111-0.967, P=0.034) and GGAG ( OR=4.616, 95% CI 1.179-18.069, P=0.016) were all correlated with the risk of PNS in children. Conclusions:AC genotype, AC+CC genotype, and C allele gene of rs3740360 SNP locus may reduce the risk of PNS in Guangxi Zhuang children. Haploid AGCG and GGCC may be associated with decreased incidence of PNS, while GGAG may be associated with increased incidence of PNS in Guangxi Zhuang children. The genotypes and alleles of 4 SNP loci are not associated with the risk of steroid-resistant nephrotic syndrome.

Phospholipase CE1 (PLCE1) is a special phospholipase C isoenzyme in the phospholipase family.It is expressed in podocytes of mature glomeruli and participates in cell signal transduction through a variety of pathways, thereby promoting its growth and expression.It has been reported that the single gene mutation of PLCE1, the heterozygosis mutation with other pathogenic genes and the interaction between PLCE1 and other factors are likely to cause primary nephrotic syndrome (PNS) in children.There have been children with PLCE1 mutation-induced steroid-resistant nephrotic syndrome cured after taking calmodulin inhibitors.They bring hope to treat PNS.In this article, the expression of PLCE1, its biological function, the mechanism of PLCE1 leading to PNS in children and its treatment were reviewed.

Objective:To analyze the mutation sites and characteristics of phospholipase CE1( PLCE1) gene in children with primary nephrotic syndrome(PNS) in Zhuang, Guangxi, China, so as to explore the expression status of PLCE1 protein in peripheral blood of PNS patients. Methods:(1)Blood samples of 154 Zhuang children with PNS and 98 healthy children of Zhuang nationality from July 2015 to September 2017 in Affiliated Hospital of Youjiang Medical College for Nationalities were collected to sequence PLCE1 gene with FastTarget target gene capture method in the combination with next generation sequencing.Based on the comparison between mutation results and information from the database, the pathogenicity, phenotype and distribution characteristics of these mutation sites were discovered and appraised.(2)The concentration of PLCE1 protein in serum samples were measured by enzyme-linked immuno sorbent assay, then the data of PNS group and healthy control group were compared and analyzed statistically with SPSS 25.0. Results:(1)A total of 18 low-frequency mutations of PLCE1 were observed, 5 of them(c.670C>T, c.578T>C, c.923G>T, c.4916C>T, and c. 5927_5929del) were found only in the PNS group, and 3 of them occurred in both PNS group and healthy control group: c.176C>T, c.389T>C, and c. 4304C>T.Five newly discovered mutations (c.923G>T, c.958T>A, c.1151C>T, c.2341A>G, and c. 3592G>C)were discovered and only c. 923 G>T is pathogenic mutation of PLCE1.(2)The concentration of PLCE1 protein in healthy control group was 414.65 (231.20, 729.81) ng/L and the level of PLCE1 in PNS group was 237.84 (116.14, 535.85) ng/L, ( Z=-3.212, P<0.001), and the value of PNS group was lower than that in the healthy control group. Conclusions:(1)As a new pathogenic mutation of PLCE1, c.923G>T was found.(2)The phenotype of PLCE1 gene mutation in Zhuang children with PNS was diverse, and they may differ by race and region.(3) PLCE1 protein of serum may act as a protective protein to guarantee various life activities of cells by participating in multiple signal transduction pathways.

Objective To investigate the expressions of β-catenin and lymphoid enhancer factor 1(LEF1) mRNA in acute leukemia(AL)and their correlation. Methods Real-time PCR was used to examine the expres-sions of β-catenin and LEF1 mRNA in 62 de novo acute myeloid leukemia(AML)patients,23 de novo acute lymphoblastic leukemia(ALL)patients,20 controls and 4 kinds of cell lines:K562,HL-60,THP-1 and Raji. Results The expression level of β-catenin in AML group was significantly higher compared with the control group,but LEF1 mRNA expression in AML group was significantly lower than that in the control group (P <0.05). The expression levels of β-catenin and LEF1 mRNA were all significantly higher in ALL group compared with the control group (P < 0.05). There were significantly positive correlations between β-catenin and LEF1 mRNA expressions both in AML and in ALL groups(P<0.05). Among the three AML cell lines,THP-1 cell had the highest β-catenin mRNA expression and the lowest LEF1 mRNA expression,and the expression tendencies of these two genes in THP-1 cell line were in accordance with those in AML patients. Conclusions Activation of Wnt/β-catenin pathway happends in AL patients and β-catenin/LEF1 may play a role in leukemogenensis of ALL.

Objective To investigate the role of CXC chemokine ligand 5 (CXCL5) in the patho-genesis of dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD). Methods A mouse model of IBD was established by giving 3% DSS in drinking water. Influences of CXCL5 knockout on mouse body weight, clinical symptoms, survival rate, pathological injury and the secretion of inflammatory cyto-kines were analyzed. Results CXCL5 levels in serum of mice with DSS-induced IBD were significantly higher than those of the normal control group. DSS-induced weight gain, death, pathological damages and inflammatory cytokine secretion were alleviated in mice after knocking out CXCL5. Conclusion CXCL5 might promote the secretion of inflammatory cytokines in mice with DSS-induced acute colitis and aggravate pathological damages,suggesting that CXCL5 might be a potentially important candidate target for the treat-ment of IBD.

Objective To explore the value of trauma-induced blood coagulation dysfunction in the evaluation of severity and prognosis of the patients with multi-trauma.Methods Eighty-two cases of multi-trauma patients admitted into the ICU of the department from June 2013 to January 2015 were chosen as the research subjects.The patients were divided into the trauma-induced coagulopathy (TIC) group(n =37)and the non-trauma-induced coagulopathy (NTIC) group (n =45),by depending on whether or not they had coagulopathy,and they were further divided into the death group (n =25) and the survival group(n =57),in view of prognosis 14 days after injury.Indices such as platelet (Plt),fibrinogen (FIB),prothrombin time (PT),activated partial thromboplastin time (APTT),thrombin time(TT) were measured within 6 hours after admission into hospital.Injury severity scores (ISS) of the subjects were evaluated 12 hours after admission,acute physiological and chronic health evaluationⅡ (APACHE Ⅱ)were performed within 24 hours after admission.Six mouths after injury,the survivors in both the TIC group and the NTIC group had medical follow-ups,and scores of Nottingham health profile (NHP) were evaluated.Results The levels of PLt and FIB in the TIC group were lower than those in the NTIC group,and the levels of PT,APTT and TT in the TIC group were all higher than those in the NTIC group,with statistical significance (P ＜ 0.01).The scores of ISS and APACHE Ⅱ in the TIC group were all significantly higher than those in the NTIC group,also with statistical significance(P ＜0.05).Fourteen days after injury,16 cases in the TIC group died (43.24％),and in the NTIC group 9 cases died (20％).Statistical significance could be noted when comparisons were made between the 2 groups (P ＜ 0.05).Six months after injury,the NHP scores of the TIC group were (97.85 ±23.17),while those of the NTIC group were (86.24 ±20.16).Statistical significance could also be noted when comparisons were made between the 2 groups(P ＜ 0.05).The levels of PLt and FIB in the death group were all higher than those in the survival group.The scores of PT,APTT and TT in the death group were higher than those in the survival group,and the scores of ISS and APACHE Ⅱ at the time of admission in the death group were all significantly higher than those in the survival group.Statistical significance could be noted,when comparisons were made between the 2 groups (P ＜ 0.01).Conclusion There was a high probability for those patients with multi-trauma to have TIC.Coagulation index was of significant importance to the diagnosis and prognosis of the patients with multiple injuries.

Objective To investigate the epidemic patterns and the characteristics of influenza in Chi-na through a Meta-analysis based on the studies published in domestic literatures.Methods Related articles published during 2005 to 2012 were screened out from domestic databases and analyzed through a Meta-analysis with Review Manager 5.0 software.Results Twenty-two articles covering 957 901 patients with influenza-like-illness (ILI) and 148 233 pathogen samples were screened out according to the inclusion criteria.No significant difference with the ILI diagnosis rate was found between subjects at age 0-4 years and those at age 15-59 years. Higher ILI diagnosis rates were observed in those two groups as compared with subjects elder than 60 years old. Most of the pathogen samples were carried by subjects aged 25-59 years.More influenza virus strains were isola-ted in 2009 as compared with those of the seven other years (OR=2.25, 95%CI=1.27-3.70).There was sta-tistical difference between the numbers of influenza A H1N1 and seasonal influenza A strains (OR=2.25, 95%CI=1.30-3.91) .Significant difference was also observed between the numbers of influenza A and influenza B strains (OR=4.05, 95%CI=2.53-6.47).Conclusion There was significant difference with the diagnosis rate between subjects aged 0-4 years and those aged≥60 years.More attention should be paid to people at high risk of infection (0-4 years old and≥60 years old) and those at 25-29 years with high mobility and social inter-course for the timely prevention and control of pandemic influenza.The detection rate of influenza virus strains was increased during the outbreak of novel influenza A H1N1 infection in 2009.After that outbreak, the detec-tion rate of novel influenza A H1N1 strains was 2.25 times the rate of seasonal influenza strains.The detection rate of influenza A was 4.05 times the rate of influenza B virus strains.Therefore, it is necessary to strengthen the surveillance for influenza A virus and other epidemic influenza virus strains.

Objective To establish adapted strain of seasonal influenza virus influenza A virus [A/ Hong Kong/1968 (H3N2)] in mice and explore the molecular mechanism of adaption preliminary.Methods The mice model was induced by nose dropping with wild type H3N2 influenza virus,by continuous passage in the lung of mice and detection of the clinical manifestation,viral load,virus titer,pathology,cytokines,to get the adapted strain of seasonal influenza A virus [A/Hong Kong/1968 (H3N2)].Results After 7 times continuous passage in the lung of mice,virulence was increased,viral load and virus titer were increased either.Genome sequencing and alignment indicated that the HA and NA gene was mutated.Conclusion The influenza virus H3N2 of mice lung adaption can be acquired from wild type seasonal H3N2 by continuous passage in the lung tissues of mice.Mutation of Ile to Val at residue 248 of HA and Val to Ile at residue 444of NA protein may be the key virulence determinant.