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Objective:To identify the Key genes in the development of sepsis through weighted gene co-expression network analysis (WGCNA).Methods:The gene expression dataset GSE154918 was downloaded from the public database Gene Expression Omnibus (GEO) database, which containes data from 105 microarrays of 40 control cases, 12 cases of asymptomatic infection, 39 cases of sepsis, and 14 cases of follow-up sepsis. The R software was used to screen out differentially expressed genes (DEG) in sepsis, and the distributed access view integrated database (DAVID), search tool for retrieval of interacting neighbouring genes (STRING) and visualization software Cytoscape were used to perform gene function and pathway enrichment analysis, Protein-protein interaction (PPI) network analysis and key gene analysis to screen out the key genes in the development of sepsis.Results:Forty-six candidate genes were obtained by WGCNA and combined with DEG expression analysis, and these 46 genes were analyzed by gene ontology (GO) and Kyoto City Encyclopedia of Genes and Genomes (KEGG) pathway enrichment to obtain gene functions and involved signaling pathways. The PPI network was further constructed using the STRING database, and 5 key genes were selected by the PPI network visualization software Cytoscape, including the mast cell expressed membrane protein 1 gene (MCEMP1), the S100 calcium-binding protein A12 gene (S100A12), the adipokine resistance factor gene (RETN), the c-type lectin structural domain family 4 member gene (CLEC4D), and peroxisome proliferator-activated receptor gene (PPARG), and differential expression analysis of each of these 5 genes showed that the expression levels of the above 5 genes were significantly upregulated in sepsis patients compared with healthy controls.Conclusion:In this study, 5 key genes related to sepsis were screened by constructing WGCNA method, which may be potential candidate targets related to sepsis diagnosis and treatment.
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Objective To establish a severe sepsis/septic shock prognosis prediction model based on randomize forest law (RF model), and to evaluate the prognostic value of this model for patients with severe sepsis/septic shock. Methods 497 patients with severe sepsis/septic shock admitted to intensive care unit (ICU) of Zhejiang Hospital from September 2013 to May 2017 were enrolled. The basic data, vital signs and symptoms, biochemical indexes and blood routine indexes on the 1st, 3rd, 5th day and prognosis were collected. According to the 28-day prognosis, the patients were divided into death group and survival group, and the specific indicators about the prognosis of severe sepsis/septic shock were screened. A RF model was constructed by using the specificity indicators. The assessment effectiveness of RF model, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ) were evaluated by receiver operating characteristic (ROC) curve analysis. Results In 497 cases of severe sepsis/septic shock, 201 cases died, 28-day mortality was 40.4%. ① According to the index difference of death group and survival group, 19 specific parameters of the RF model were selected, which included the age; 24-hour urine output, urea nitrogen (BUN), serum creatinine (SCr), platelet count (PLT) on the 1st day; heart rate (HR), mean arterial pressure (MAP), cyanosis and clammy skin on the 3rd day; temperature, HR, MAP, 24-hour urine output, PLT, fever, cyanosis, dyspneic, clammy skin, piebald on the 5th day. ② ROC curve analysis showed that the area under the ROC curve (AUC) of RF model predicting 28-day mortality was higher than that of SOFA and APACHE Ⅱ score on the 1st, 3rd, 5th day (AUC: 0.836 vs. 0.643, 0.554, 0.766 and 0.590, 0.670, 0.758). The sensitivity of RF model to predict the 28-day mortality was 86.1%, the specificity was 77.0%, the accuracy was 80.7%. Conclusion The evaluation model based on random forest can effectively predict the death risk of 28-day in patients with severe sepsis/septic shock, and its predictive efficiency is better than that of the SOFA and APACHE Ⅱ score.
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Objective To investigate urine adiponectin changes and related factors in different stage of type-2 diabetic ne-phropathy.Methods A total of 1 1 9 DN patients admitted to the Yongchuan Hospital of Chongqing Medical University in 2013 were selected.The general indices and laboratory examination results were retrospectively analyzed.1 1 9 type-2 diabetic nephropathy patients were divided into normal Proteinuria group,micro-Proteinuria group,macro-Proteinuria group,according to urine albumin excretion rate in 24 hours.45 health subjects from Physical examination center were enrolled as normal group.The UAER of the three groups were compared and the correlation between each index and UAER was analyzed.Results Urine adiponectin levels in normal Proteinuria group was significantly lower than micro-Proteinuria group(P <0.01)and macro-Proteinuria group(P <0.01). Urine adiponectin levels in micro-Proteinuria group was significantly lower than macro-Proteinuria group (P <0.01)and higher than normal group(P < 0.01 ).Urine adiponectin levels in macro-Proteinuria group were significantly higher than normal group (P <0.01 ).Multiple linear regression analysis showed that HDL-C,FPG,HbA1c and UAER had effects on the levels of Urine adiponec-tin.Conclusion Urinary adiponectin levels are associated with type 2 diabetic nephropathy,and which was related with HDL-C, FPG,HbA1c and UAER.
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Objective To investigate the role of damaged mitochondria in cardiac cell apoptosis in septic rats and the possible mechanism involved.Methods Seventy-two Sprague-Dawley rats were randomly (random number) divided into negative control group (n =18) and septic group (further divided into three groups as per rats sacrificed 6 h,12 h,and 24 h after endotoxin injection intra-peritoneally,n =18).The hearts of rats were taken.The changes of cardiac morphology were observed under light microscope and scanning electron microscope.Cell apoptosis in situ were examined by using terminal transferase-mediated dUTP nick end-labeling assay and nuclear factor-kappa B (NF-κB) activation in myocardium was detected by using Western blotting to estimate myocardial cell apoptosis.Mitochondrial lipid and protein oxidation were measured to assess oxidative stress,and mitochondrial superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were determined to estimate antioxidant defense.Results Septic induced inflammatory cells infiltration,myocardium degeneration and effusion in a time-dependent manner.A remarkable expansion of capillaries could be observed in the hearts of infected rats at post-challenge of 24 h.Compared with sham-treated rats,the percentage of apoptosis increased in a time-dependent manner in the hearts of infected rats at 6 h,12 h,24 h of post-injection (P ＜0.05).The concentration of NF-κB p65 in the cytosol decreased gradually and increased in the nucleus during sepsis in a time-dependent manner (P ＜0.05),indicating that septic challenge provoked progressive activation of NF-κB.Mitochondrial cristae disappeared in 6 h of challenge,and significant mitochondrial cristae disappearance,vacuolization,and rupture of mitochondria membrane became markedly obvious 12 and 24 h later.Both SOD and GPx activities decreased,while mitochondrial lipid and protein oxidation increased in a time-dependent manner after 6-24 h of challenge (P ＜ 0.05).Conclusions Septic challenge induced myocardial apoptosis and mitochondrial damage.Further,damaged mitochondria might play an important role by means of alteration of defenses against reactive oxygen species in myocardial cell apoptosis during sepsis.