Comprehensive analysis of an autophagy-related prognostic model for predicting survival based on TCGA and ICGC database in hepatocellular carcinoma patients.

Background: There is accumulating evidence that autophagic activity is crucial to the development of hepatocellular carcinoma (HCC). Thus, we sought to develop a predictive model based on autophagy-related genes (ARGs) to forecast the prognosis of HCC patients. Methods: Based on expression data from The Cancer Genome Atlas (TCGA) and ARGs from Human Autophagy Database (HADb), the differentially expressed ARGs were screened. The prognosis-related ARGs were identified using a univariate Cox regression analysis. Using multivariate Cox regression analysis, a prognostic model was developed. To assess the predictive value of the model, receiver operating characteristic (ROC) curve, Kaplan-Meier curve, and multivariable Cox regression analyses were conducted. A data cohort gathered independently from the International Cancer Genome Consortium (ICGC) database further verified the model's predictive accuracy. The immune landscape was generated using the TIMER and CIBERSORT algorithms. Finally, the correlation between the prognostic signature and gene mutation status was analyzed by employing "maftools" package. Results: We identified a novel prediction model based on the ARGs of PLD1 and SLC36A1 with significant prognostic values for HCC in both univariate and multivariate Cox regression analysis, and patients were classified into high- or low-risk groups based on their risk scores. High-risk patients had significantly shorter overall survival (OS) times than low-risk patients (P=5e-4). According to the ROC curve analysis, the risk score had a higher predictive value than the other clinical characteristics. Prognostic nomograms were also performed to visualize the relationship between individual predictors and survival rates in patients with HCC. Further, an external independent cohort of ICGC patients provided additional confirmation of the predictive efficacy of the model. We subsequently analyzed the differential immune densities of the two groups and discovered that various immune cells, including naïve B cells, resting memory cluster of differentiation (CD)4 T cells, regulatory T cells, M2 macrophages, and neutrophils, had considerably larger infiltrating densities in the high-risk group than the low-risk group. Conclusions: We established a robust autophagy-related risk model having a certain prediction accuracy for predicting the prognosis of HCC patients. Our findings will contribute to the definition of prognosis and establishment of personalized treatment interventions for HCC patients.

Changes in peripheral blood inflammatory factors (TNF-α and IL-6) and intestinal flora in AIDS and HIV-positive individuals.

OBJECTIVE: In this study, we investigated the changes in peripheral blood inflammatory factors and intestinal flora in acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV)-positive individuals (AIDS/HIV patients), and explored the relationships among intestinal flora, peripheral blood inflammatory factors, and CD4+ T lymphocytes. METHODS: Thirty blood and stool samples from an AIDS group and a control group were collected. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA), and the number of CD4+ T lymphocytes by a FACSCount automated instrument. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the messenger RNA (mRNA) levels of Bifidobacterium, Lactobacillus, Escherichia coli, Enterococcus faecalis, and Enterococcus faecium. Correlations among intestinal flora, inflammatory factor levels, and CD4+ T lymphocyte values were evaluated using the Spearman correlation coefficient. RESULTS: The levels of TNF-α and IL-6 in the AIDS group were higher than those in the control group, while the number of CD4+ T lymphocytes was lower. The amounts of Bifidobacterium and Lactobacillus in the AIDS group were significantly lower than those in control group, while the amounts of E. coli, E. faecalis, and E. faecium were much higher. The amounts of Bifidobacterium and Lactobacillus were negatively correlated with the content of TNF-α and IL-6 and the CD4+ T lymphocyte count, while those correlations were reversed for E. coli, E. faecalis, and E. faecium. CONCLUSIONS: The intestinal microbiota of AIDS/HIV patients were disordered, and there was a correlation between the amount of intestinal flora and the number of CD4+ T lymphocytes and the levels of TNF-α and IL-6.

Field population-based blocking treatment of esophageal epithelia dysplasia.

AIM: To confirm the value of blocking treatment by zenshengping (ZSP), a Chinese herb composite, and Riboflavin for esophageal epithelia dysplasia cases screened out in high risk area in northern china by exfoliative balloon cytology (EBC), so to reduce the incidence rate of esophageal cancer(EC). METHODS: Esophageal epithelium dysplasia cases including mind esophageal epithelium dysplasia (MEED), stage one severe esophageal epithelium dysplasia (SEED I), and stage two severe esophageal epithelium dysplasia (SEED II) were screened out from people aged 40 years and older in the high risk area of Chixian. These cases were randomly divided into a treatment and control group. Subjects in the treatment and control groups took ZSP, riboflavin, and placebo daily for three years. EC cases registered by cancer registry and identified by EBC re-screening in the treatment and control groups were used to calculate incidence and blocking rates to demonstrate the effects of blocking medication. RESULTS: It was found that 31.92% and 24.15% of people aged 40 years and older in Cixian could been diagnosed as MEED and SEED cases. The severity of dysplasia increased with age. ZSP had blocked EC occurrence by 47.79% after 3 year medication among the SEED cases. CONCLUSION: ZSP can block the development from SEED I and SEED II to EC by 47.79%. Efforts should be made to screen and treat dysplasia cases in people aged 40 years and older in high risk areas to reduce the mortality figures.

[Flow injection analysis of trace amounts of doxycycline with inhibited chemiluminescence detection].

A novel flow injection chemiluminescence method has been developed for the determination of doxycycline (DC) based on the inhibition of chemiluminescence reaction of Luminol-KMnO4 by using DC in sodium hydroxide medium. Using different concentrations of KMnO4, a series of good linear regression equations of decreased chemiluminescence intensity and the concentration of DC were obtained with different subsections in the concentration range of 0.005-5.0 microg x mL(-1). The detection limit (3sigma) is 2.0 x 10(-3) microg x mL(-1). The method has been successfully applied to the determination of DC in a pharmaceutical preparation.

Chemiluminescence determination of melatonin and some of its derivatives using potassium permanganate and formaldehyde system.

It was found that melatonin and its derivatives, such as N-acetyl- 5-methoxytryptamine (MT), N-acetyl-5-hydroxytryptamine (NAS), 5-Methoxytrypt- amine (5-MT), 5-Methoxyindolyl acetic acid (5-MIAA) and N-acetyl-5-methoxy- 6-hydroxytryptamine (6-HMT) would give chemiluminescence in the acidic potassium permanganate solution, and formaldehyde would enhance this chemiluminescent reaction greatly. The optimum conditions for this chemiluminescent reaction were studied in detail by a flow injection system. A new simple rapid method has been developed under the optimum conditions for determination of melatonin. This method has the advantages of high sensitivity, wide range of linear response and low detection limit. On the basis of investigation of chemiluminescent, fluorescent and UV spectra of melatonin in acidic solution containing potassium permanganate and formaldehyde, a possible mechanism of this reaction was proposed.