Vascular endothelial growth factor receptor-2 and its association with tumor immune regulatory gene expression in hepatocellular carcinoma.

Anti-vascular endothelial growth factor (anti-VEGF) drugs have long been the only first-line treatment for advanced or unresectable hepatocellular carcinoma (HCC). Recently, the combination of bevacizumab (an anti-VEGF drug) and atezolizumab (an immune checkpoint blockade, ICB) has been proven to have superior efficacy over sorafenib. However, the complex association between VEGF signaling pathway and tumor immune microenvironment is still largely unknown. Here, we analyzed the RNA sequencing and clinical data of 365 HCC patients obtained from The Cancer Genome Atlas to investigate the potential correlation between VEGF signaling pathway and tumor immune microenvironment, including immune cell infiltration, 66 immune markers, genomic instability, and immune-related pathways. Our study revealed that VEGF signaling pathway score was positively correlated with immune cell infiltration and the expression profile of 66 immune markers. Enrichment analysis indicated that genes differentially expressed between two VEGF score subtypes were enriched in many immune-related Gene Ontology terms. Most importantly, both VEGF signaling pathway and activated CD8+ T cells were positively correlated with prognosis. Our findings suggest the co-activation of VEGF signaling pathway and tumor immune microenvironment in HCC patients, indicating the underlining mechanism of combination therapy including anti-VEGF drugs and ICBs.

Characterization of biofilm formation by Enterococcus faecalis isolates derived from urinary tract infections in China.

Purpose. This study explored the prevalence and characteristics of Enterococcus faecalis biofilm formation by urinary tract infection (UTI) isolates in order to identify virulence factors associated with biofilm formation.Methodology. A total of 113 E. faecalis isolates were collected from UTI patients in Shenzhen, China. The isolates were subjected to multilocus sequence typing based on housekeeping genes. Biofilms were detected by crystal violet staining and the expression levels of the E. faecalis genes were detected by quantitative real-time PCR.Results/Key findings. The main sequence types (STs) were ST16 and ST179 with the ST16 isolates more likely to form strong biofilms than the ST179 isolates (P=0.008). Strong biofilm formation was more frequently detected in aggregation substance (agg)-positive (+) isolates than in negative (-) isolates (P=0.033). Biofilm formation was also more common in isolates containing enterococcal surface protein (esp), or cytolysin A (cylA)-positive (+) isolates than in isolates negative (-) for these virulence factors. Multivariate regression analysis indicated that cylA [odds ratio (OR), 7.143, P=0.012] was associated with weak biofilm formation, and that agg (OR, 4.471, P=0.004) was associated with strong biofilm formation. The expression of cylA was increased (8.75- to 23.05-fold) in weak biofilm, and the expression of agg was greatly elevated (11.99- to 439.10-fold) in strong biofilm isolates when compared to biofilm-negative isolates.Conclusion. ST16 classification was positively associated with strong biofilm formation in E. faecalis as was agg, while cylA was associated with weak biofilm formation.

Characteristics of and Virulence Factors Associated with Biofilm Formation in Clinical Enterococcus faecalis Isolates in China.

Enterococcus faecalis biofilm traits and distribution characteristics in China have not been clarified. This study aimed to determine the prevalence and characteristics of E. faecalis biofilm formation in a sample of clinical isolates and to explore the virulence factors associated with biofilm formation in those isolates. A total of 265 E. faecalis isolates were collected from patients in Shenzhen, China. Virulence genes were detected within the genomes of the microbes by polymerase chain reaction. The isolates were subjected to multilocus sequence typing (MLST) based on housekeeping genes. Biofilms were detected by crystal violet staining. The expression levels of the clinical E. faecalis isolates' genes were determined by quantitative real-time polymerase chain reaction. The prevalence of biofilm formation among E. faecalis clinical isolates was 47.2%. MLST yielded 44 different sequence types (STs). The main STs were ST16 and ST179; the ST16 isolates were more likely to form strong or medium biofilm than the ST179 isolates (p < 0.001). Strong or medium biofilm formation was more common in linezolid-resistant isolates than in linezolid-sensitive isolates (p = 0.001). Biofilm formation was more frequently detected in enterococcal surface protein (esp+), surface aggregating protein (asa1+), cytolysin A (cylA+), or aggregation substance (agg+) positive isolates than in isolates that were negative (-) for these virulence factors. Multivariate regression analysis indicated that cylA [odds ratio (OR) 4.083, p < 0.001] was a risk factor for weak biofilm formation, and that esp (OR 8.207, p < 0.001) was a risk factor for strong or medium biofilm formation. The expression of cylA was raised (4.02 to 6.00-fold) in weak biofilm isolates compared to the biofilm-negative isolates, and the expression of esp was greatly elevated (11.39 to 134.08-fold) in strong biofilm isolates compared to biofilm-negative isolates. In conclusion, the ST16 classification and linezolid resistance were positively associated with strong/medium biofilm formation in clinical E. faecalis isolates. cylA was associated with weak biofilm formation, and esp was only associated with strong or medium biofilm formation of the clinical E. faecalis isolates.

Bloodstream infections caused by Enterococcus spp: A 10-year retrospective analysis at a tertiary hospital in China.

In order to discover the risk factors for 30-day mortality in bloodstream infections (BSI) caused by Enterococcus spp. strains, we explored the clinical and therapeutic profile of patients with Enterococcus spp. BSI and the characteristics of this condition. A total of 64 patients with BSI caused by Enterococcus spp. who were treated in our hospital between 2006 and 2015 were included in the study. The clinical features of patients, microbiology, and 30-day mortality were collected from the electronic medical records database and analyzed. The results showed that there were 38 patients infected by Enterococcus faecalis (E. faecalis), 24 by Enterococcus faecium (E. faecium), 1 by Enterococcus casseliflavus (E. casseliflavus), and 1 by Enterococcus gallinarum (E. gallinarum). A Charlson comorbidity score ≥5, corticosteroid treatment, placement of catheters or other prosthetic devices and history of antibiotic use were found more frequently in E. faecium BSI patients than in E. faecalis patients (P=0.017, P=0.027, P=0.008 and P=0.027, respectively). Furthermore, the univariate and multivariate analysis showed that corticosteroid treatment (OR=17.385, P=0.008), hospital acquisition (OR=16.328, P=0.038), and vascular catheter infection (OR=14.788, P=0.025) were all independently associated with 30-day mortality. Our results indicate that E. faecalis and E. faecium are two different pathogens with unique microbiologic characteristics, which cause different clinical features in BSI, and the empiric antimicrobial treatments are paramount for patients with enterococcal BSI.

Bloodstream Infections Caused by Enterococcus spp: A 10-year Retrospective Analysis at a Tertiary Hospital in China / 华中科技大学学报（医学）（英德文版）

In order to discover the risk factors for 30-day mortality in bloodstream infections (BSI) caused by Enterococcus spp.strains,we explored the clinical and therapeutic profile of patients with Enterococcus spp.BSI and the characteristics of this condition.A total of 64 patients with BSI caused by Enterococcus spp.who were treated in our hospital between 2006 and 2015 were included in the study.The clinical features of patients,microbiology,and 30-day mortality were collected from the electronic medical records database and analyzed.The results showed that there were 38 patients infected by Enterococcus faecalis (E.faecalis),24 by Enterococcus faecium (E.faecium),1 by Enterococcus casseliflavus (E.casseliflavus),and 1 by Enterococcus gallinarum (E.gallinarum).A Charlson comorbidity score ≥5,corticosteroid treatment,placement of catheters or other prosthetic devices and history of antibiotic use were found more frequently in E.faecium BSI patients than in E.faecalis patients (P=0.017,P=0.027,P=0.008 and P=0.027,respectively).Furthermore,the univariate and multivariate analysis showed that corticosteroid treatment (OR=17.385,P=0.008),hospital acquisition (OR=16.328,P=0.038),and vascular catheter infection (OR=14.788,P=0.025) were all independently associated with 30-day mortality.Our results indicate that E.faecalis and E.faecium are two different pathogens with unique microbiologic characteristics,which cause different clinical features in BSI,and the empiric antimicrobial treatments are paramount for patients with enterococcal BSI.