Objective To investigate the mechanism of action of macrophage-derived exosomes(Exo)in peripheral nerve injury(PNI).Methods Exo were extracted following the polarization of macrophages to either the M1 or M2 phenotype to determine their effects on Schwann cells(SCs),using cell proliferation,quantitative real-time polymerase chain reaction,flow cytometry,RNA sequencing,and Western blot.A sciatic nerve extrusion model was established in vivo.PBS,M1-exo and M2-exo treatment groups were injected with PBS,M1-exo,and M2-exo,respectively,and a separate normal group was set up.The sciatic nerve function index(SFI),wet weight ratio,and staining of neuromuscular tissue were evaluated on a weekly basis in each experimental group following surgical intervention.Results M1-exo facilitated SC migration and upregulated glial-derived nerve growth factor,whereas M2-exo promoted SC proliferation and migration and upregulated brain-derived nerve growth factor and nerve growth factor.The biomarkers,myelin protein zero,glial fibrillary acidic protein,nerve growth factor receptor(NGFR)and S100 calcium-binding protein B(S100)were also detected.In the in vivo experiments,the SFI,wet weight ratio,neuromuscular tissues,and fluorescent areas of nerve axons(marker NF200)and SCs(marker S100)were all significantly better in the M2-exo treatment group at week 4 compared with the PBS treatment group,while there were no significant differences between the M1-exo and PBS treatment groups.Both the in vivo and ex vivo experiments demonstrated that M2-exo facilitated the proliferation of SCs via phosphorylation of the serine/threonine kinase AKT,resulting in downregulation of the cell cycle protein WEE 1.Conclusions M2-exo has been demonstrated to promote up-regulation of genes associated with nerve regeneration by SCs and promote SC proliferation and migration,thereby facilitating nerve regeneration via the AKT-WEE1 pathway.

Objective To investigate the mechanism of action of macrophage-derived exosomes(Exo)in peripheral nerve injury(PNI).Methods Exo were extracted following the polarization of macrophages to either the M1 or M2 phenotype to determine their effects on Schwann cells(SCs),using cell proliferation,quantitative real-time polymerase chain reaction,flow cytometry,RNA sequencing,and Western blot.A sciatic nerve extrusion model was established in vivo.PBS,M1-exo and M2-exo treatment groups were injected with PBS,M1-exo,and M2-exo,respectively,and a separate normal group was set up.The sciatic nerve function index(SFI),wet weight ratio,and staining of neuromuscular tissue were evaluated on a weekly basis in each experimental group following surgical intervention.Results M1-exo facilitated SC migration and upregulated glial-derived nerve growth factor,whereas M2-exo promoted SC proliferation and migration and upregulated brain-derived nerve growth factor and nerve growth factor.The biomarkers,myelin protein zero,glial fibrillary acidic protein,nerve growth factor receptor(NGFR)and S100 calcium-binding protein B(S100)were also detected.In the in vivo experiments,the SFI,wet weight ratio,neuromuscular tissues,and fluorescent areas of nerve axons(marker NF200)and SCs(marker S100)were all significantly better in the M2-exo treatment group at week 4 compared with the PBS treatment group,while there were no significant differences between the M1-exo and PBS treatment groups.Both the in vivo and ex vivo experiments demonstrated that M2-exo facilitated the proliferation of SCs via phosphorylation of the serine/threonine kinase AKT,resulting in downregulation of the cell cycle protein WEE 1.Conclusions M2-exo has been demonstrated to promote up-regulation of genes associated with nerve regeneration by SCs and promote SC proliferation and migration,thereby facilitating nerve regeneration via the AKT-WEE1 pathway.

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.

Urinary tract infection(UTI)is a common disease of the urinary system. Based on a case of male outpatient with primary acute uncomplicated pyelonephritis and the relevant guidelines, this article analyzes the identification, diagnosis and differential diagnosis as well as comprehensive management of uncomplicated upper urinary tract infection, in order to provide information and clinical thinking for general practitioners.