Identification of key genes for predicting colorectal cancer prognosis by integrated bioinformatics analysis.

Colorectal cancer (CRC) is a life-threatening disease with a poor prognosis. Therefore, it is crucial to identify molecular prognostic biomarkers for CRC. The present study aimed to identify potential key genes that could be used to predict the prognosis of patients with CRC. Three CRC microarray datasets (GSE20916, GSE73360 and GSE44861) were downloaded from the Gene Expression Omnibus (GEO) database, and one dataset was obtained from The Cancer Genome Atlas (TCGA) database. The three GEO datasets were analyzed to detect differentially expressed genes (DEGs) using the BRB-ArrayTools software. Functional and pathway enrichment analyses of these DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery tool. A protein-protein interaction (PPI) network of DEGs was constructed, hub genes were extracted, and modules of the PPI network were analyzed. To investigate the prognostic values of the hub genes in CRC, data from the CRC datasets of TCGA were used to perform the survival analyses based on the sample splitting method and Cox regression model. Correlation among the hub genes was evaluated using Spearman's correlation analysis. In the three GEO datasets, a total of 105 common DEGs were identified, including 51 down- and 54 up-regulated genes in CRC compared with normal colorectal tissues. A PPI network consisting of 100 DEGs and 551 edges was constructed, and 44 nodes were identified as hub genes. Among these 44 genes, the four hub genes TIMP metallopeptidase inhibitor 1 (TIMP1), solute carrier family 4 member 4 (SLC4A4), aldo-keto reductase family 1 member B10 (AKR1B10) and ATP binding cassette subfamily E member 1 (ABCE1) were associated with overall survival (OS) in patients with CRC. Three significant modules were extracted from the PPI network. The hub gene TIMP1 was present in Module 1, ABCE1 was involved in Module 2 and SLC4A4 was identified in Module 3. Univariate analysis revealed that TIMP1, SLC4A4, AKR1B10 and ABCE1 were associated with the OS of patients with CRC. Multivariate analysis demonstrated that SLC4A4 may be an independent prognostic factor associated with OS. Furthermore, the results from correlation analysis revealed that there was no correlation between TIMP1, SLC4A4 and ABCE1, whereas AKR1B10 was positively correlated with SLC4A4. In conclusion, the four key genes TIMP1, SLC4A4, AKR1B10 and ABCE1 associated with the OS of patients with CRC were identified by integrated bioinformatics analysis. These key genes may be used as prognostic biomarkers to predict the survival of patients with CRC, and may therefore represent novel therapeutic targets for CRC.

Antimicrobial resistance and pathogen distribution in hospitalized burn patients: A multicenter study in Southeast China.

Burn infections pose a serious obstacle to recovery. To investigate and analyze the antimicrobial resistance and distribution of pathogenic bacteria among hospitalized burn patients. A 3-year retrospective study was conducted in the southeast of China.The electronic medical records system was used to collect all clinical data on 1449 hospitalized patients from Fujian Medical University Union Hospital, the 180th Hospital of Chinese People's Liberation Army (PLA), the 92nd Hospital of PLA, and the First Hospital of Longyan City.A total of 1891 strains of pathogenic bacteria were detected from 3835 clinical specimens, and the total detection rate was 49.3% (1891/3835). The main pathogens were gram-negative bacteria (1089 strains; 57.6%), followed by gram-positive bacteria (689 strains; 36.4%), and fungi (113 strains; 6.0%). The predominant five bacteria were Staphylococcus aureus (19.0%), Acinetobacter baumannii (17.6%), Pseudomonas aeruginosa (16.7%), Klebsiella pneumoniae (7.4%), and Enterococcus faecalis (4.5%). Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 74.1% (265/359) of S aureus isolates. Staphylococcus epidermidis accounted for 40.6% (69/170) of coagulase-negative staphylococcal isolates, 72.5% (50/69) of which were methicillin-resistant Staphylococcus epidermidis (MRSE). Both MRSA and MRSE were 100% resistant to penicillin and ampicillin. A baumannii was the most commonly isolated strain of gram-negative bacteria with 100% resistance to ampicillin, amoxicillin, amoxicillin/clavulanic acid, and aztreonam. More than 80% of K pneumoniae isolates were resistant to ampicillin, amoxicillin and cefazolin. More than 80% of Escherichia coli isolates were resistant to ampicillin, piperacillin, cefazolin, amoxicillin, tetracycline, and sulfamethoxazole trimethoprim. The detection rates of extended-spectrum ß-lactamases (ESBL) among K pneumoniae and E coli isolates were 44.6% (62/139) and 67.2% (41/61), respectively. Low-resistance antibiotics included teicoplanin, tigecycline, vancomycin, and linezolid.The pathogens presented high resistance to antimicrobial agents, especially MRSA and A baumannii. Monitoring of bacterial population dynamics should be established to inhibit the progression of bacterial resistance.

[Role of IgG plasma cells in the change of protein C system in ulcerative colitis].

The present study is designed to explore the role of plasma cells in the change of protein C system (PCS) in ulcerative colitis (UC). Dextran sulfate sodium (DSS, 4% in concentration) was used to induce mouse UC model. The plasma cells and the type of immune complex in colon were observed by immunofluorescence. The amount and type of plasma cells separated from colonic mucosal lamina propria were detected by flow cytometry using anti-CD54+CD38+ and IgA/M/G antibodies, respectively. After stimulation of macrophages by IgG type immune complex, TNF-α and IL-6 levels were evaluated by ELISA. After co-incubation of microvascular endothelial cells with TNF-α or IL-6, the expressions of endothelial protein C receptor (EPCR) and thrombomodulin (TM), and the activity of activated protein C (APC) were examined. As the results showed, the IgG type plasma cells infiltration and the quantity of IgG type immune complex were increased in DSS group in comparison with control group. After incubation with IgG type immune complex, the levels of TNF-α and IL-6 in the supernatant of macrophages were increased (P < 0.01) in a concentration-dependent manner. Meanwhile, after incubation with TNF-α or IL-6, the expressions of EPCR and TM in the microvascular endothelial cells were decreased (P < 0.05 or P < 0.01), while the activity of APC was reduced (P < 0.05 or P < 0.01). These results suggested that the quantity of IgG type plasma cells increases in UC and forms immune complexes, which affect the secretion of cytokines from macrophage, thereby affecting the function of endothelial cells and finally inhibiting PCS in UC. Therefore, plasma cell may be a novel target for the treatment of UC.

Duodenal-jejunal exclusion improves insulin resistance in type 2 diabetic rats by upregulating the hepatic insulin signaling pathway.

OBJECTIVES: Previous studies have shown duodenal-jejunal exclusion (DJE) results in the rapid resolution of type 2 diabetes; however, the underlying mechanism is unknown. This study aimed to measure the hepatic expression of insulin receptor substrate-2 (IRS-2) and glucose transporter-2 (GLUT-2) in type 2 diabetic rats post-DJE, and to investigate their roles in improved hepatic insulin resistance and glucose intolerance. METHODS: Type 2 diabetic Sprague-Dawley (SD) rats were randomly divided into DJE operation (DO) and control (DC) groups. Normal SD rats were also divided into DJE operation and control groups. Fasting plasma glucose and insulin concentrations were measured, and the quantitative insulin sensitivity check index (QUICKI) and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) were calculated. Eight weeks postoperation, the hepatic IRS-2 and GLUT-2 protein and mRNA levels were measured using western blotting and reverse transcription polymerase chain reaction, respectively. RESULTS: The fasting blood glucose in the DO group decreased from a preoperative level of 20.21 ± 2.14 mmol/L to 8.50 ± 2.19 mmol/L (P < 0.05) 8 wk post-DJE. A change in the QUICKI revealed a dramatic increase, and HOMA-IR showed a significant decrease in the DO group (P < 0.05). Additionally, the IRS-2 and GLUT-2 protein and mRNA levels at 8 wk postoperation were significantly increased in the DO group compared with the DC group. CONCLUSIONS: DJE led to upregulated hepatic IRS-2 and GLUT-2 expression in the hepatic insulin signaling pathway and improved insulin sensitivity in type 2 diabetic rats.