Background: Growing evidence has suggested that immune-related genes play crucial roles in the development and progression of hepatocellular carcinoma (HCC). Nevertheless, the utility of immune-related genes for evaluating the prognosis of HCC patients are still lacking. The study aimed to explore gene signatures and prognostic values of immune-related genes in HCC. Methods:We comprehensively integrated gene expression data acquired from 374 HCC and 50 normal tissues in The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) analysis and univariate Cox regression analysis were performed to identify DEGs that related to overall survival. An immune prognostic model was constructed using the Lasso and multivariate Cox regression analyses. Furthermore, Cox regression analysis was applied to identify independent prognostic factors in HCC. The correlation analysis between immune-related signature and immune cells infiltration were also investigated. Finally, the signature was validated in an external independent dataset.Results: A total of 329 differentially expressed immune-related genes were detected. 64 immune-related genes were identified to be markedly related to overall survival in HCC patients using univariate Cox regression analysis. Then we established a TF-mediated network for exploring the regulatory mechanisms of these genes. Lasso and multivariate Cox regression analyses were applied to construct the immune-based prognostic model, which consisted of nine immune-related genes. Further analysis indicated that this immune-related prognostic model could be an independent prognostic indicator after adjusting to other clinical factors. The relationships between the risk score model and immune cell infiltration suggested that the nine-gene signature could reflect the status of tumor immune microenvironment. The prognostic value of this nine-gene prognostic model was further successfully validated in an independent database.Conclusions: Together, our study screened potential prognostic immune-related genes and established a novel immune-based prognostic model of HCC, which not only provides new potential prognostic biomarkers and therapeutic targets, but also deepens our understanding of tumor immune microenvironment status and lays a theoretical foundation for immunotherapy.
The aim of this study was to determine the effects of combinations of fosfomycin, minocycline and polymyxin B in the treatment of pan-drug-resistant Acinetobacter baumannii (PDR-Ab). The in vitro antibacterial activities of the drugs were evaluated by determination of the minimum inhibitory concentration (MIC) and the fractional inhibitory concentration index (FICI). A total of 25 strains of PDR-Ab were selected using the VITEK32 microbial analysis instrument and the Kirby-Bauer (K-B) method. A broth microdilution method was used to determine the MIC for each of the three drugs, and the checkerboard method was simultaneously used to determine the MICs for combinations of the drugs. FICI values were also calculated. While fosfomycin alone was ineffective for the treatment of PDR-Ab, its MIC value was significantly reduced when used in combination with minocycline or polymyxin B. The combined use of minocycline and polymyxin B also significantly reduced the MIC value of each drug. The FICI values revealed that the drugs had synergistic or additive effects when used in combination. The determination of the MIC and FICI values for the combinations of drugs demonstrated that there is synergistic or additive effect upon the combined use of fosfomycin with minocycline or polymyxin B. The combined use of minocycline and polymyxin B also results in a significant reduction in the MIC values of the two drugs. These experimental results may provide a basis for the future clinical treatment of Acinetobacter baumannii.
The aim of this study was to investigate the in vitro activities of rifampin, colistin, sulbactam and tigecycline alone and in combination against extensively drug-resistant Acinetobacter baumannii (XDR-Ab). Twenty-five XDR-Ab strains were isolated from patients. Broth microdilution assay was used to determine the minimum inhibitory concentration (MIC) for rifampin, colistin, sulbactam and tigecycline against XDR-Ab strains. The checkerboard microdilution method was used to determine the in vitro activities of potential therapeutic combinations of these four antimicrobial agents. Accordingly, the fractional inhibitory concentration (FIC) and FIC index (FICI) were calculated for each of the combinations. According to our results, when tested as single drugs, rifampin, colistin or tigecycline had good bacteriostatic activity against XDR-Ab, whereas sulbactam was not as active against XDR-Ab isolates. On the other hand, when tested in combination, the combinations of colistin/rifampin, rifampin/sulbactam, rifampin/tigecycline and sulbactam/tigecycline showed good in vitro activities against XDR-Ab isolates. More importantly, these combination regimens could exert addictive or partially synergistic effects at the sub-MIC levels against XDR-Ab strains. Compared with single drugs, most of the combinations of these antimicrobial agents could exert partially synergistic and/or addictive effects, which might provide a better alternative when treating XDR-Ab infections.
Background: Brucellosis is endemic in many areas in China. The current diagnosis of Brucellosis predominantly relies on the traditional bacterial culture and serum agglutination test. In this study, we aimed to explore the value of ELISA in the diagnosis of Brucellosis in Chinese population. Methods: We recruited 235 patients with a diagnosis of Brucellosis at different clinical stages: 117 in acute, 78 in subacute, and 40 in chronic. We also recruited 248 control patients who presented with similar clinical symptoms but with a different diagnosis other than Brucellosis. In addition, 90 healthy volunteers were also recruited. Bacterial culture, agglutination test and ELISA assay were performed to detect Brucella spp. Results: Among 235 patients with Brucellosis, 51 (21.7%) was positive for bacterial culture, 150 (63.8%) were positive by agglutination test, and 232 (98.7%) were positive by ELISA (IgG and/or IgM). When we stratified the patients based on the disease stages (acute, subacute and chronic), ELISA was the most sensitive method and showed a highest positive rate in all stages. By Receiver Operating Characteristic Curve analysis of ELISA results, we found that measurement of IgG level was superior to measurement of IgM level (AUC, 0.993 versus 0.877). Since the measurement of IgG itself missed rare cases in acute phase, we recommended measuring IgG and IgM simultaneously by ELISA for the diagnosis of Brucellosis. In term of the specificity of ELISA in the diagnosis of Brucellosis, our study showed that only 1.6% (4/248) non-Brucellosis patients were positive by ELISA; all positive cases were IgM only and none showed positive IgG. Similar results were found in healthy volunteers. In summary, our study concluded that ELISA is the most sensitive and specific method to detect Brucellosis in Chinese population. Conclusions: ELISA assay is sensitive, fast, and convenient to detect Brucellosis. It shows the high sensitivity and specifity and should be used as a routine lab test when Brucellosis is suspected in clinical practice.
Background Atopic dermatitis is a chronic inflammatory disease of the skin. It has a high prevalence worldwide and affected persons are prone to recurrent attacks, seriously affecting the physical and mental of patients. The exact etiology of the disease is still unclear. Material/Methods There are 7 datasets on atopic dermatitis in the Gene Expression Omnibus database, including 142 lesional and 134 non-lesional skin biopsy samples. Differential analysis was performed after datasets were integrated by robust multi-array average method. Functional modules of GSE99802 were explored by weighted gene co-expression network analysis. The 4 most important modules were enriched into the pathways by Metascape. Results Significantly differentially expressed genes included 41 upregulated and 10 downregulated genes. The following 5 of the most important upregulated genes had the strongest association with atopic dermatitis. SERPINB3&4 promote inflammation and impaired skin barrier function in the early stage of atopic dermatitis. S100A9 aggravates the inflammatory response by inducing the activation of toll-like receptor 4, neutrophil chemotaxis, neutrophilic inflammation, and the amplification of interleukin-8. MMP1 is the key protease of skin collagen degradation, keeping the extracellular matrix in dynamic balance. MMP12 induces the aggregation of various inflammatory cells into inflammatory tissue. The enriched pathways of each module mainly include Cellular responses to external stimuli, Metabolism of RNA and Translation, and Infectious disease. Conclusions The associated pathways and genes not only help us understand the molecular mechanism of the disease, but also provide research directions or targets for accurate diagnosis and treatment.
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