A novel plasma proteomic-based model for predicting liver fibrosis in HIV/HBV co-infected adults.

To establish a plasma model to predict the risk of liver fibrosis in HIV/HBV co-infected individuals. Quantitative liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to identify differentially expressed proteins (DEPs) in plasma collected from HIV/HBV co-infected individuals with and without liver fibrosis. In total, 97 DEPs were identified, among which 11 were further validated as potential biomarkers, with immunoglobulin and complement components being the most common proteins. These markedly altered proteins were found to mediate pathophysiological pathways, including humoral immune response, complement and coagulation cascades, and complement activation. A visual logistic model, in which immunoglobulin heavy variable 3-20 (IGHV3-20), immunoglobulin heavy variable 1-24 (IGHV1-24), and macrophage colony-stimulating factor 1 receptor (CSF1R) proteins were included, has been established to predict liver fibrosis in HIV/HBV co-infected individuals. The preliminary conclusion showed that the combination of IGHV3-20, IGFHV1-24, and CSF1R is expected to become a predictive model for liver fibrosis in the context of HIV/HBV co-infection and a further validation should be performed.

Analysis of melanoma tumor antigens and immune subtypes for the development of mRNA vaccine.

Melanoma has a high degree of malignancy and mortality. While there are some hopeful clinical trials for melanoma treatment in progress, they have not yet to yield significant long-term cure rates. Cancer vaccines including mRNA are currently one of the most promising strategy for tumor immunotherapy. The aim of this study was to analyze the potential tumor antigens in melanoma that could be used to develop mRNA vaccines and identify suitable vaccine populations. The gene expression data and complete clinical information of 471 melanoma samples and 1 normal tissue were retrieved from TCGA. Then, 812 samples of normal skin and their corresponding gene expression data were obtained from GTEx. Overexpressed genes, mutated genes and IRDEGs are used to identify potential tumor antigens. The relationship between the expression level of potential antigen and prognosis was analyzed in GEPIA, and then the immune cell infiltration was estimated based on TIMER algorithm. The expression profiles of IRDEGs were used to identify consensus clusters and immune subtypes of melanoma. Finally, mutational status and immune microenvironment characterization in immune subtypes were analyzed. Five tumor antigens (PTPRC, SIGLEC10, CARD11, LILRB1, ADAMDEC1) were identified as potential tumor antigens according to overexpressed genes, mutated genes and immune-related genes. They were all associated with OS, DFS and APCs. We identified two immune subtypes of melanoma, named IS1 and IS2, which exhibit different clinical features and immune landscapes. Based on the different immune landscape, we may conclude that IS1 is immunophenotypically "cold", while IS2 is "hot". The present research implicates that PTPRC, SIGLEC10, CARD11, LILRB1 and ADAMDEC1 may be the antigenic targets for melanoma mRNA vaccines and IS2 patients may be more effective to these vaccines.

Efficacy of Ivabradine versus ß-Blockers for Heart Rate Reduction during Computed Tomography Coronary Angiography: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To quantify the efficacy of pretreatment with ivabradine compared to ß-blockers before computed tomography coronary angiography (CTCA) via a meta-analysis of clinical randomized controlled trial data. METHODS: We conducted a search for randomized controlled trials of pretreatment with ivabradine compared to ß-blockers before CTCA in Medline, PubMed, Embase, SCI/SSCI/A&HCI, SAS Publishers, Web of Science, and the Cochrane Central Register. The Jadad quality score of the included studies, and the mean difference (MD) in heart rate reduction, were indicators of efficacy. RevMan 5.2 and Stata 12.0 software were used for the meta-analysis. RESULTS: Eight studies involving a total of 1,324 patients were included in the final analysis. The results showed that ivabradine was significantly more effective at improving the heart rate of patients achieving the target heart rate (<65 bpm) during CTCA (OR 5.02; 95% CI 3.16-7.98, p < 0.00001, I2 = 20%). A comparison of efficacy between ivabradine and ß-blockers showed a statistically significant effect of ivabradine on heart rate reduction during CTCA (MD -4.39; 95% CI -4.80 to -3.99, p < 0.00001, I2 = 0%). Ivabradine also led to a significant reduction in heart rate prior to CTCA (MD -5.33; 95% CI -10.26 to -0.39, p = 0.03, I2 = 92%). In terms of the total reduction in heart rate during CTCA, significant differences were noted between the ivabradine group and the ß-blocker group (MD 2.64; 95% CI 1.25-4.02, p = 0.0002, I2 = 0%). The mean percentage reduction in heart rate in the ivabradine group was significantly higher than that in the ß-blocker group (MD 7.18; 95% CI 5.64-8.72, p < 0.00001, I2 = 43%). Ivabradine had no significant effect on either systolic blood pressure (BP) (MD 11.41; 95% CI 6.43-16.40, p < 0.00001, I2 = 85%) or diastolic BP (MD 1.79; 95% CI -0.00 to 3.58, p = 0.05, I2 = 56%). CONCLUSION: Compared to ß-blockers for heart rate reduction, ivabradine is a potentially attractive alternative for patients undergoing CTCA.

Bioinformatics Analysis of the Prognostic Significance of VPS16 in Hepatocellular Carcinoma and Its Role in Drug Screening.

Background: Vacuolar protein sorting 16 (VPS16) overexpression was recently considered related to cancer growth and drug resistance; however, little is known about whether VPS16 plays a vital role in liver hepatocellular carcinoma (LIHC). Methods: The TIMER2 online database was used to analyze the expression of VPS16 in pancancer, and the Xena Browser was used to explore the correlation between VPS16 expression level and survival time. R language was used to test the survival data of 374 LIHC cases in the TCGA database. DESeq2 was used for differentially expressed gene (DEG) analysis. The HPA database was used to verify the expression level of VPS16 in LIHC. The clusterProfiler package was used to analyze functions and related signaling pathways via GO/KEGG enrichment analysis. Drug sensitivity analysis and molecular docking technology were used to screen the most sensitive drugs targeting VPS16 molecules. Results: Pancancer analysis showed that VPS16 was highly expressed in various tumors, especially in LIHC. With the increase in the T stage and grade of LIHC, the expression level of VPS16 was also increased. The expression of VPS16 was negatively correlated with the overall survival of LIHC patients. The stage can be used as an independent prognostic factor. A total of 63 sensitive drugs were found, and 19 drugs were displaying strong molecular binding energy with VPS16. Conclusion: VPS16 may be a potential biomarker for the diagnosis and prognosis of LIHC. Drugs targeting VPS16 may be used in the treatment of LIHC in the future.

A Novel Ferroptosis-Related lncRNAs Signature Predicts Clinical Prognosis and Is Associated With Immune Landscape in Pancreatic Cancer.

Pancreatic cancer is one of the most lethal malignancies and currently therapies are severely lacking. In this study, we aimed to establish a novel ferroptosis-related lncRNAs signature to predict the prognosis of patients with pancreatic cancer and evaluate the predictive abilities of candidate lncRNAs. According to The Cancer Genome Atlas (TCGA) database, a total of 182 patients with pancreatic cancer were included in our study. Ferroptosis-related lncRNAs were screened by Pearson correlation analysis with 60 reported ferroptosis-related genes. Through univariate, least absolute shrinkage and selection operator (LASSO) regression and multivariate regression analyses, a novel signature based on five ferroptosis-related lncRNAs(ZNF236-DT, CASC8, PAN3-AS1, SH3PXD2A-AS1, LINP1) was constructed. Risk-related differentially expressed genes (DEGs) were subjected to enrichment analyses for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The results revealed that immune cell infiltration, immune-related functions and checkpoints were factors to affect prognoisis of pancreatic cancer. In summary, we identified the prognostic ferroptosis-related lncRNAs(ZNF236-DT, CASC8, PAN3-AS1, SH3PXD2A-AS1, LINP1) in pancreatic cancer and these lncRNAs may serve as therapeutic targets for pancreatic cancer.

Cell death and pathological findings of the spleen in COVID-19 patients.

The coronavirus disease 2019(COVID-19) is recognized as systemic inflammatory response syndrome. It was demonstrated that a rapid increase of cytokines in the serum of COVID-19 patients is associated with the severity of disease. However, the mechanisms of the cytokine release are not clear. By using immunofluorescence staining we found that the number of CD11b positive immune cells including macrophages in the spleens of died COVID-19 patients, was significantly higher than that of the control patients. The incidence of apoptosis as measured by two apoptotic markers, TUNEL and cleaved caspase-3, in COVID-19 patients' spleen cells is higher than that in control patients. By double immunostaining CD11b or CD68 and SARS-CoV-2 spike protein, it was found that up to 67% of these immune cells were positive for spike protein, suggesting that viral infection might be associated with apoptosis in these cells. Besides, we also stained the autophagy-related molecules (p-Akt、p62 and BCL-2) in spleen tissues, the results showed that the number of positive cells was significantly higher in COVID-19 group. And compared with non-COVID-19 patients, autophagy may be inhibited in COVID-19 patients. Our research suggest that SARS-CoV-2 may result in a higher rate of apoptosis and a lower rate of autophagy of immune cells in the spleen of COVID-19 patients. These discoveries may increase our understanding of the pathogenesis of COVID-19.

Suspected myocardial injury in patients with COVID-19: Evidence from front-line clinical observation in Wuhan, China.

BACKGROUND: A novel coronavirus disease (COVID-19) in Wuhan has caused an outbreak and become a major public health issue in China and great concern from international community. Myocarditis and myocardial injury were suspected and may even be considered as one of the leading causes for death of COVID-19 patients. Therefore, we focused on the condition of the heart, and sought to provide firsthand evidence for whether myocarditis and myocardial injury were caused by COVID-19. METHODS: We enrolled patients with confirmed diagnosis of COVID-19 retrospectively and collected heart-related clinical data, mainly including cardiac imaging findings, laboratory results and clinical outcomes. Serial tests of cardiac markers were traced for the analysis of potential myocardial injury/myocarditis. RESULTS: 112 COVID-19 patients were enrolled in our study. There was evidence of myocardial injury in COVID-19 patients and 14 (12.5%) patients had presented abnormalities similar to myocarditis. Most of patients had normal levels of troponin at admission, that in 42 (37.5%) patients increased during hospitalization, especially in those that died. Troponin levels were significantly increased in the week preceding the death. 15 (13.4%) patients have presented signs of pulmonary hypertension. Typical signs of myocarditis were absent on echocardiography and electrocardiogram. CONCLUSIONS: The clinical evidence in our study suggested that myocardial injury is more likely related to systemic consequences rather than direct damage by the 2019 novel coronavirus. The elevation in cardiac markers was probably due to secondary and systemic consequences and can be considered as the warning sign for recent adverse clinical outcomes of the patients.