Objective To investigate the pharmacodynamic effects of Poria triterpenes on tumor suppression in mice with ascites tumors,and to detect and identify the chemical components of Poria triterpenes using HPLC-LTQ-Orbitrap method,and to explore the potential mechanism of action of Poria triterpenes on tumor suppression in mice with ascites tumors based on both of them using non-labeled definitive proteomics techniques.Methods Poria triterpene parts were extracted by solvent method,and the main components were detected and identified by HPLC-LTQ-Orbitrap liquid mass spectrometer;mice were randomly divided into model group,Poria triterpene group and positive control group(mushroom polysaccharide group),after 21 days of continuous administration,to establish After continuous administration for 21 days,the H22 ascites tumor mouse model was established,and the effect of each drug group on the amount of ascites,spleen index,thymus index,liver index,serum TNF-Alpha and IL-2 in H22 ascites tumor mice was observed after one week of continued administration;then H22 cells were extracted from the ascites of mice,and the H22 cells in the model group and Poria triterpene group were detected by non-lable-free quantitative proteomics technique.The differentially expressed proteins(DEPs)were screened out by using GO,KEGG and other analyses.Results The abdominal water volume in the mouse Poria triterpene group was significantly lower than that in the model group(P<0.05);the thymus index in the mouse Poria triterpene group was significantly higher than that in the model group(P<0.05);the serum levels of TNF-Alpha in the mouse Poria triterpene group were significantly different from those in the model group(P<0.01),and the serum levels of IL-2 in the mouse Poria triterpene group were significantly different from those in the model group(P<0.01).Through the analysis of the chemical composition of Poria triterpene parts,a total of 19 triterpenoids were identified,with four main structural types.A total of 188 differentially expressed proteins were identified in the Poria triterpene group compared with the model group,of which 86 differentially expressed proteins were up-regulated and 102 differentially expressed proteins were down-regulated;GO database analysis showed that the differentially expressed proteins in the Poria triterpene group were mainly involved in the regulation of interleukin-1 production The KEGG database analysis showed that the differentially expressed proteins in the Poria triterpene group were involved in signaling pathways closely related to tumor,mainly MAPK,Apoptosis,mTOR,Wnt and p53 pathways,etc.The genes coding for the seven representative differential proteins were validated at the mRNA level by RT-qPCR.Conclusion The pharmacodynamic study found that Poria triterpenes had tumor suppressive effect on H22 ascites tumor mice,then by proteomics found Poria triterpenes group ascites H22 cell protein compared to the model group changed significantly,the study thus showed that Poria triterpenes for mice ascites tumor mechanism of tumor suppressive effect mainly involves apoptosis,inflammatory response and immune process.

Objective:To clarify the key genes and biological processes in spermatogenesis, integrate and analyze the differentially expressed genes (DEGs) and key signaling pathways in the differentiation process of human spermatogonia (SPG), and to explore the early molecular mechanism of spermatogenesis, increase the molecular biology understanding of SPG differentiation process.Methods:The transcriptome data of human undifferentiated spermatogonia and differentiated spermatogonia (dSPG) were downloaded from the public database. Hisat2 and StingTie were used to screen DEGs. DEGs were analyzed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) functional enrichment analysis. MACS2 software was used to analyze the open chromatin regions (OCRs) in ATAC-seq data.Results:A total of 8 532 DEGs were screened, including 4 127 up-regulated genes and 4 405 down-regulated genes. They regulate the differentiation of SPG through some important biological processes, such as cell cycle, cytokine-mediated signaling pathways, organic matter metabolism, cell movement, and methylation. KEGG enrichment analysis showed that some important signaling pathways including FoxO signaling pathway and JAK-STAT signaling pathway played an important role in SPG differentiation. GO enrichment analysis showed that methylation played an important role in the differentiation of SPG, and the expression of methylation-related genes was significantly different. The TDRDs family was significantly enriched, and 9 TDRDs genes were found to be more active in dSPG. Conclusion:In this study, the differentially expressed genes during SPG differentiation were identified by bioinformatics analysis, and the differences in transcription and chromatin levels of key genes were clarified, which laid an important theoretical foundation for the study of SPG differentiation mechanism.

Objective:To clarify the key genes and biological processes in spermatogenesis, integrate and analyze the differentially expressed genes (DEGs) and key signaling pathways in the differentiation process of human spermatogonia (SPG), and to explore the early molecular mechanism of spermatogenesis, increase the molecular biology understanding of SPG differentiation process.Methods:The transcriptome data of human undifferentiated spermatogonia and differentiated spermatogonia (dSPG) were downloaded from the public database. Hisat2 and StingTie were used to screen DEGs. DEGs were analyzed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) functional enrichment analysis. MACS2 software was used to analyze the open chromatin regions (OCRs) in ATAC-seq data.Results:A total of 8 532 DEGs were screened, including 4 127 up-regulated genes and 4 405 down-regulated genes. They regulate the differentiation of SPG through some important biological processes, such as cell cycle, cytokine-mediated signaling pathways, organic matter metabolism, cell movement, and methylation. KEGG enrichment analysis showed that some important signaling pathways including FoxO signaling pathway and JAK-STAT signaling pathway played an important role in SPG differentiation. GO enrichment analysis showed that methylation played an important role in the differentiation of SPG, and the expression of methylation-related genes was significantly different. The TDRDs family was significantly enriched, and 9 TDRDs genes were found to be more active in dSPG. Conclusion:In this study, the differentially expressed genes during SPG differentiation were identified by bioinformatics analysis, and the differences in transcription and chromatin levels of key genes were clarified, which laid an important theoretical foundation for the study of SPG differentiation mechanism.

Objective:To assess the interobserver and inter-modalities agreement with two non-invasive diagnostic modalities of hepatocellular carcinoma in high-risk patients: contrast-enhanced ultrasound liver imaging reporting and data system (CEUS LI-RADS) and magnetic resonance imaging liver imaging reporting and data system (MRI LI-RADS).Methods:From August 2017 to August 2019, the CEUS and MRI data of patients at high risk for HCC from the Second Affiliated Hospital of Zhejiang University School of Medicine were analyzed retrospectively. A total of 217 lesions in 173 patients were classified according to CEUS LI-RADS v. 2017 or MRI LI-RADS v. 2018, by 4 blinded independent observers with more than 10 years of experience of CEUS or MRI. Interobserver and inter-modalities agreement was assessed with Cohen′s kappa.Results:The interobserver agreement was moderate and comparable for CEUS/MRI LI-RADS category (κ=0.606/0.603), the inter-modalities agreement was moderate for CEUS and MRI LI-RADS category (κ=0.564), LI-RADS 3, M, 4 and 5 by two imaging methods showed that the Kappa values were 0.739, 0.551, 0.734 and 0.592, respectively.Conclusions:The total inter-modalities agreement between CEUS and MRI LI-RADS categories is moderate, while the agreements of LI-RADS 3, 4 are strong, and LI-RADS M, 5 are moderate.