PurposeThe purpose of this study was to assess the efficacy and toxicities of adding molecular targeted agents (MTAs) to first-line chemotherapy in the treatment of advanced biliary tract cancer (BTC).MethodsAn extensive search for relevant clinical trials was conducted in electronic databases (PubMed, Web of Science, and Cochrane) and abstracts presented at meetings. Prospective randomized controlled trials (RCTs) reporting the efficacy and toxicity of chemotherapies with or without MTAs in advanced BTC were selected. The endpoints were overall survival (OS), progression-free survival (PFS), and grade 3 or 4 toxicities. The results were expressed as hazard ratio or relative risk (RR), with their corresponding 95% confidence intervals.ResultsThe final analysis included a total of 855 advanced BTC patients from six RCTs. Compared with chemotherapy alone, the combination of MTAs with chemotherapy significantly improved overall response rate (ORR) (RR 1.68, 95% confidence interval: 1.28–2.19, P<0.001). And there was also a tendency to improve PFS in the combination regimens (hazard ratio 0.89, 95% confidence interval: 0.78–1.02, P=0.097) but not for OS (hazard ratio 1.01, 95% confidence interval: 0.90–1.13, P=0.93). Subgroup analysis according to targeted agents indicated that the addition of anti-epidermal growth factor receptor agents to chemotherapy significantly improved ORR and PFS, but it did not translate into OS benefits. Additionally, equivalent frequencies of grade 3 or 4 neutropenia, anemia, thrombocytopenia, nausea, and vomiting were found between the two groups excepting for diarrhea.ConclusionThe present study indicates that the addition of anti-epidermal growth factor receptor agents to first-line chemotherapy in advanced BTC offers an improved ORR and PFS, but not for OS. Further RCTs with larger samples are warranted to confirm our findings.

Background: Atherosclerosis (AS) seriously affects human health. The role of microRNAs (miRNAs) in the pathogenesis and progression of AS has become a focus of research. Our goal was to identify the biological effect of differentially expressed miRNAs (DE-miRNAs) in AS. Methods:To analyze differentially expressed genes (DEGs), including differentially expressed mRNAs (DE-mRNAs) and DE-miRNAs, in AS by using the Gene Expression Omnibus (GEO) database and limma package. DEGs protein-protein interaction (PPI) network and functional enrichment analysis were constructed by using the search tool for the retrieval of interacting genes/proteins (STRING) database, Cytoscape software and Cytoscape plugin "ClueGO2.5.6". We established a coexpression network of dysregulated miRNAs and mRNAs to predict the function of miRNAs by using miRWalk database and Pearson correlation coefficient (PCC) analysis. Cellular experiments were used to validate the results of bioinformatics.Results: First, 69 common DEGs were obtained from datasets GSE43292 and GSE97210 using the limma package in R. Next, a DEG PPI network was constructed. Functional enrichment analysis of DEGs showed that 11 functional pathways were significantly enriched, such as positive regulation of monocyte chemotaxis.Seven common DE-miRNAs were obtained from the GSE99685 dataset and DE-mRNAs predicted miRNAs through the miRWalk database. The miRNA-mRNA network constructed using Cytoscape software suggested that miR-148a-3p targeted contactin 4 (CNTN4). Quantitative real-time polymerase chain reaction (qRT-PCR) assay results indicated that miR-148a-3p was downregulated and CNTN4 was upregulated in the THP-1 + phorbol 12-myristate 13-acetate (PMA) + oxidized low-density lipoprotein (oxLDL) group compared with the THP-1 + PMA group. qRT-PCR, flow cytometry, and ELISA found that upregulated miR-148a-3p significantly inhibited the expression of CNTN4, cell apoptosis, and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) concentrations in oxLDL-induced THP-1 macrophages. In addition, a dual-luciferase reporter assay demonstrated that CNTN4 was a target gene of miR-148a-3p.Conclusions: Overall, these findings suggested that miR-148a-3p inhibited oxLDL-induced cell apoptosis and inflammation via targeting CNTN4 in THP-1 macrophages.

Purpose: To evaluate the efficacy of three-dimensional arterial spin labeling (3D-ASL) imaging in preoperative grading of brain gliomas, and compare the discrepancy between images obtained from 3D-ASL and contrast enhanced magnetic resonance imaging (CE-MRI) in grading of gliomas.Methods: Fifty-one patients with brain gliomas received plain MRI, CE-MRI and 3D-ASL scanning before surgery. In 3D-ASL images, the maximum tumor blood flow (TBF) of tumor parenchyma was measured, relative TBF-M and rTBF-WM were calculated. The cases were categorized into "ASL dominant" and "CE dominant" to compare the discrepancy between 3D-ASL and CE-MRI results. Independent samples t test, Mann-Whitney and U test and one-way analysis of variance (ANOVA) were performed to test the differences of TBF, rTBF-M and rTBF-WM values among brain gliomas with different grades. Spearman rank correlation analysis was performed to assess the correlation between TBF, rTBF-M, rTBF-WM and glioma grades respectively. To compare the discrepancy between 3D-ASL and CE-MRI results.Results: In high-grade gliomas (HGG) group, TBF, rTBF-M and rTBF-WM values were higher than those in low-grade gliomas (LGG) group (p < .05). Multiple comparison showed TBF and rTBF-WM values were different between grade I and IV gliomas, grade II and IV gliomas (both p < .05), the rTBF-M value was different between grade I and IV gliomas (p < .05). The values of all 3D-ASL derived parameters were positively correlated with gliomas grading (all p < .001). TBF showed highest specificity (89.3%) and rTBF-WM showed highest sensitivity (96.4%) when discriminating LGG and HGG using ROC curve. There were 29 CE dominant cases (23 cases were HGG), 9 ASL dominant cases (4 cases were HGG).Conclusion: 3D-ASL is of significance to preoperative grading of brain gliomas and might be more sensitive than CE-MRI in detection of tumor perfusion.