Retrospective studies have suggested that capecitabine combined with temozolomide (CAPTEM) is effective for treating patients with advanced neuroendocrine neoplasms (NENs); however, the efficacy and safety of this regimen needs to be verified by high-quality evidence or results of randomized controlled trials.We carried out a meta-analysis to evaluate the safety and effectiveness of a CAPTEM protocol for patients with advanced NENs. Systematic electronic literature searches were conducted using PubMed, EMBASE, and the Cochrane Library, and among meeting abstracts of the American Society of Clinical Oncology, European Society for Medical Oncology, European Neuroendocrine Tumor Society, and North American Neuroendocrine Tumor Society, up to June 30, 2017. We selected studies describing CAPTEM regimens for treating advanced NENs and reported on tumor response and/or toxicities according to clear World Health Organization (WHO) grading of patients. Three reviewers independently and repeatedly identified studies, extracted data, and assessed the quality of the literature. A single-proportion meta-analysis was applied to included articles.Fifteen studies with a total of 384 individuals were included. Medium overall survival in most studies was more than 12 months, whereas medium progression-free survival was similar or slightly higher than that in studies using other treatment regimes. Disease control rate of CAPTEM administration for patients with NENs was 72.89% (95% confidence interval, 64.04–81.73%; I2 = 82.4%; P < .01). WHO grade 3 to 4 toxicities, such as thrombocytopenia (3.36%), neutropenia (0.69%), lymphopenia (0.65%), anemia (0.59%), mucositis (0.57%), fatigue (0.54%), diarrhea (0.49%), nausea (0.39%), and transaminase elevation (0.13%) were reported in the trials included.CAPTEM is effective and relatively safe for treating patients with advanced NENs.

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Purpose: Cisplatin (DDP) based chemotherapy regimens are widely used in advanced gastric cancer (GC). Drug resistance often limited the clinical benefits of cisplatin regimen. The mechanisms of cisplatin resistance have not been fully revealed. Therefore, further exploration of the relevant molecular mechanisms is urgently needed. Patients and methods: DDP resistance associated miRNA of GC microarray dataset GSE86195 was obtained from the National Center for Biotechnology Information (NCBI) GEO database, GEO2R was applied to compare the samples in two different groups under the same experimental conditions. |log 2 (Fold Change) | (log 2 (FC)) was selected as the criteria to screen the statistically significant DE-miRNAs. StarBaseV3.0 was used to predict the target genes of the DE-miRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of target genes of DE-miRNAs were carried out using DAVID. The STRING database was applied to estimate the correlations between target genes. Analysis of hubgenes by coremine and The Human Protein Atlas (THPA). Initial expression validations of miR-424 and miR-491-5p, SMURF1 and BCL2L1 were carried out using clinical pathological specimens by RT-PCR. Results: A total of 13 Differential expression-miRNAs (DE-miRNAs) were identified in DDP chemoresistant cells, including 9 upregulated miRNAs and 4 downregulated miRNAs. SMURF1 and BCL2L1 were screened as the critical genes in DDP-resistant GC, which were regulated by miR-424 and miR-491-5p respectively. The results of validation of hub genes expression in GC tissues indicated that in DFS<1-year group, the expression of miR-424 decreased significantly, notably upregulated expression of SMURF1 was also detected. Conclusion: Our results implied that miR-424, as a tumor suppressor, could deregulate SMURF1 in DDP-resistant GC cells.

ObjectiveAs a chronic neurodegenerative disorder, Alzheimer’s disease (AD) is the most common form of progressive dementia. The purpose of this study was to identify diagnostic signatures of AD and the effect of immune cell infiltration in this pathology.MethodsThe expression profiles of GSE109887, GSE122063, GSE28146, and GSE1297 were downloaded from the Gene Expression Omnibus (GEO) database to obtain differentially expressed genes (DEGs) between AD and control brain samples. Functional enrichment analysis was performed to reveal AD-associated biological functions and key pathways. Besides, we applied the Least Absolute Shrinkage Selection Operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) analysis to screen potential diagnostic feature genes in AD, which were further tested in AD brains of the validation cohort (GSE5281). The discriminatory ability was then assessed by the area under the receiver operating characteristic curves (AUC). Finally, the CIBERSORT algorithm and immune cell infiltration analysis were employed to assess the inflammatory state of AD.ResultsA total of 49 DEGs were identified. The functional enrichment analysis revealed that leukocyte transendothelial migration, cytokine receptor interaction, and JAK-STAT signaling pathway were enriched in the AD group. MAF basic leucine zipper transcription factor F (MAFF), ADCYAP1, and ZFP36L1 were identified as the diagnostic biomarkers of AD with high discriminatory ability (AUC = 0.850) and validated in AD brains (AUC = 0.935). As indicated from the immune cell infiltration analysis, naive B cells, plasma cells, activated/resting NK cells, M0 macrophages, M1 macrophages, resting CD4+ T memory cells, resting mast cells, memory B cells, and resting/activated dendritic cells may participate in the development of AD. Additionally, all diagnostic signatures presented different degrees of correlation with different infiltrating immune cells.ConclusionMAFF, ADCYAP1, and ZFP36L1 may become new candidate biomarkers of AD, which were closely related to the pathogenesis of AD. Moreover, the immune cells mentioned above may play crucial roles in disease occurrence and progression.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS) and a CD4+ T cell-mediated autoimmune disease. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is recognized as the major mechanism that regulates the differentiation and function of T helper (Th) 1 and Th17 cells, which are recognized as pivotal effector cells responsible for the development of EAE. We used baricitinib, a JAK 1/2 inhibitor, to investigate the therapeutic efficacy of inhibiting the JAK/STAT pathway in EAE mice. Our results showed that baricitinib significantly delayed the onset time, decreased the severity of clinical symptoms, shortened the duration of EAE, and alleviated demyelination and immune cell infiltration in the spinal cord. In addition, baricitinib treatment downregulated the proportion of interferon-γ+CD4+ Th1 and interleukin-17+CD4+ Th17 cells, decreased the levels of retinoic acid-related orphan receptor γ t and T-bet mRNA, inhibited lymphocyte proliferation, and decreased the expression of proinflammatory cytokines and chemokines in the spleen of mice with EAE. Furthermore, our results showed the role of baricitinib in suppressing the phosphorylation of STATs 1, 3, and 4 in the spleen of EAE mice. Therefore, our study demonstrates that baricitinib could potentially alleviate inflammation in mice with EAE and may be a promising candidate for treating MS.