Phosphoproteomic analysis of human umbilical venous endothelial cells with DENV-2 infection / 南方医科大学学报

OBJECTIVE@#To analyze the differentially phosphorylated proteins in DENV-2-infected human umbilical venous endothelial cells (HUVECs) and explore the possible pathogenic mechanism of DENV-2 infection.@*METHODS@#The total proteins were extracted from DENV-2-infected HUVECs and blank control HUVEC using SDT lysis method. The phosphorylated proteins were qualitatively and quantitatively analyzed using tandem mass spectrometry (TMT). The identified differentially phosphorylated proteins were analyzed by bioinformatics analyses such as subcellular localization analysis, GO enrichment analysis, KEGG pathway analysis and protein-protein interaction (PPI) analysis. Western blotting was used to detect the expressions of phosphorylated Jun, map2k2 and AKT1 proteins in DENV-2-infected HUVECs.@*RESULTS@#A total of 2918 modified peptides on 1385 different proteins were detected, and among them 1346 were significantly upregulated (FC > 1.2, P < 0.05) and 1572 were significantly downregulated (FC < 0.83, P < 0.05). A total of 49 phosphorylated conserved motifs were obtained by amino acid conservative motif analysis. The most abundant differentially phosphorylated peptides in protein domain analysis included RNA recognition motif, protein kinase domain and PH domain. Subcellular localization analysis showed that the differentially modified peptides were mainly localized in the nucleus and cytoplasm. GO enrichment and KEGG pathway analysis showed that the differential peptides were mainly enriched in the regulation of stimulation response, biosynthesis of small molecules containing nuclear bases, and migration of phagosomes and leukocytes across the endothelium. PPI and KEGG joint analysis showed that the up-regulated and down-regulated differentially phosphorylated proteins were enriched in 15 pathways. In DENV-2-infected HUVECs, Western blotting detected differential expressions of phosphorylated proteins related with the autophagy pathway, namely JUN, MAP2K2 and AKT1, and among them p-JUN was significantly down-regulated and p-AKT1 and p-MAP2K2 were significantly upregulated (P < 0.01).@*CONCLUSION@#DENV-2 infected HUVECs show numerous differentially expressed proteins. The downregulation of p-JUN and upregulation of p-MAP2K2 and p-AKT1 suggest their potential roles in regulating autophagy, which is probably involved in the mechanism of DENV-2 infection.

Bibliometric Study on Health Utility Value Obtained by Mapping Method in Pharmacoeconomic Evaluation / 中国药房

OBJECTIVE：To know about the research status of health utility value obtained by mapping method in pharmacoeconomic evaluation ，and to provide reference for bibliometric study in pharmacoeconomic evaluation . METHODS ： Using“Mapping method ”“Health utility value ”“Cost-utility”“Utility point system ”as Chinese and English keywords ，retrieved from CNKI ，Wanfang database ，PubMed，Medline，Ebsco，Ovid and Wiley database ，empirical journal documents published from the inception to Dec. 31st，2018 about using mapping method to obtain health utility value were collected. The bibliometrics was used to statistically analyze basic information of included literature ，the construction and test of the model ，the type of the best model and so on. RESULTS ：The 124 included documents were all published in English journal. In the construction and testing of the mapping model ，the most frequently used econometric methods ，performance evaluation indicators and model testing methods were ordinary least squares （OLS），mean absolute error （MAE）and residual normality test ，application frequency of which were 97 times（31.60％），89 times（24.93％）and 62 times（21.09％）. There are 117 articles that define the best mapping model ，of which 101 articles（86.32％）have the best direct mapping effect. Most of the non-utility measurement scales adopted specific scales （92 articles，77.97％），and a few literatures adopted the universal scale （26 articles，22.03％）. The most utility measurement scales were 3-level European 5-dimensional health scale （79 articles，66.95％）. CONCLUSIONS ：The domestic empirical researches that use the mapping method to obtain health utility values need to be developed yet. A series of mapping models successfully developed by foreign scholars not only provide the feasibility of using non-utility measurement scales for cost-utility analysis ，but also provide more ideas for China to choose the corresponding econometric methods ，evaluation indicators and mapping methods in the empirical research of the mapping method in the future.