Objective Using bioinformatics methods to study the immune infiltration mechanism of Primary Sj?gren's syndrome(pSS)and to explore potential target Chinese medicines,which can provide new directions for the clinical treatment of pSS.Methods Gene expression profile microarray dataset of pSS was downloaded from the GEO database,differential genes were screened using R software,and gene ontology(GO)and gene pathway enrichment(KEGG)enrichment analysis was performed on these differential genes.Protein interaction network analysis of differential genes was performed by applying the STRING database,key genes were screened by using Cytoscape,and ELISA for the verification of key genes expression.Immune infiltration and correlation of immune cells in pSS were calculated by CIBERSORT inverse convolution method in 22.Finally,the herbal prediction of key target genes was performed by using the Coremine Medical database.Results A total of 232 differential genes were obtained,of which 207 were up-regulated and 25 were down-regulated.GO was mainly enriched in:leukocyte mediated immunity,lymphocyte mediated immunity,leukocyte cell-cell adhesion,etc;KEGG was mainly enriched in Hematopoietic cell lineage,Primary immunodeficiency,Intestinal immune network for IgA production,Phagosome,Leishmaniasis.Ten key genes were screened:PTPRC,CD19,LCP2,CCR5 and CD69 etc.The hub genes expression in the pSS is the same as that of GSE40611.Immune infiltration showed that memory B cells,T cells CD4 memory activated,and T cells CD4 na?ve were highly expressed in the pSS.Immune cell correlation analysis showed a positive correlation between initial Monocytes and T cells regulatory(Tregs),a positive correlation between Macrophages M1 and B cell na?ve,and a negative correlation between Plasma cells and T cells CD4 memory activated.COREMINE Medical predicted that Ginseng,Panax notoginseng,Tripterygium wilfordii,Burnet,Magnolia,and Strychni may treat pSS.Conclusion The development and progression of pSS are the results of the combined involvement of multiple genes and pathways.Memory B cells,T cells CD4 memory activated,and T cells CD4 na?ve may promote the development of pSS.The predicted Ginseng,Panax notoginseng,Tripterygium wilfordii,Burnet,Magnolia,Strychni may be used as target herbs for the potential treatment of pSS.

BACKGROUND:This study provided insight into the molecular mechanisms by which exogenous basic fibroblast growth factor(bFGF)promotes wound healing. OBJECTIVE:To investigate the effect of exogenous bFGF on macrophage phenotype transition and granulation regeneration during wound repair in rats. METHODS:(1)In vitro experiment:Cells were divided into normal control group,low-dose bFGF group,high-dose bFGF group,and bFGF+valproic acid group.100 and 200 μg/L bFGF was added into the cell culture medium of low-dose bFGF group and high-dose bFGF group,respectively,while 200 μg/L bFGF and 20 mmol/L valproic acid were added into the cell culture medium of valproic acid group.EdU test,scratch test and tubule formation test were used to detect the effects of bFGF on proliferation,migration and angiogenesis of human umbilical vein endothelial cells.(2)In vivo experiment:Sprague-Dawley rats were randomly divided into model group,low-dose bFGF group,high-dose bFGF group and bFGF+valproic acid group.The open wound model of full-thickness skin defect was established in low-dose bFGF group,high-dose bFGF group and bFGF+valproic acid group.Rats in the low-and high-dose bFGF groups were given 100 and 200 μg/L bFGF through subcutaneous injection,while those in the bFGF+valproic acid group received subcutaneous injection of 200 μg/L bFGF and intraperitoneal injection of 10 mg/kg valproic acid.The wound healing rate of rats was detected at 7 and 14 days of administration.TUNEL was used to detect the apoptosis of cells in wound tissue.Enzyme linked immunosorbent assay was used to detect the serum levels of malondialdehyde,superoxide dismutase,tumor necrosis factor-α and interleukin-10.Immunofluorescence detection was conducted to detect the phenotypic transformation of macrophages in wound tissue.Immunohistochemistry was used to detect the expression of proliferating cell nuclear antigen,platelet endothelial cell adhesion molecule-1(CD31)and vascular endothelial growth factor in wound tissue.Western blot was used to detect the expression of Notch1 and Jagged1 in wound tissue. RESULTS AND CONCLUSION:(1)Compared with the normal control group,bFGF could significantly promote the proliferation,migration and angiogenesis of human umbilical vein endothelial cells in a dose-dependent manner.(2)Compared with the model group,bFGF could significantly promote wound healing,downregulate the rate of apoptosis in wound tissue,decrease the levels of malondialdehyde and tumor necrosis factor-α in serum,increase the levels of superoxide dismutase and interleukin-10,promote the conversion of macrophages to type M2 in wound tissue,upregulate the expression of proliferating cell nuclear antigen,CD31 and vascular endothelial growth factor in wound tissue,and inhibit the expression of Notch1 and Jagged1 in a dose-dependent manner.Valproic acid could partially reverse the promoting effect of bFGF on wound healing.To conclude,bFGF can significantly promote wound healing and granulation regeneration and induce the conversion of macrophages to M2,which may be related to the regulation of Notch1/Jagged1 signaling pathway.

Objective:Using bioinformatics methods to study the immune infiltration mechanism of lupus nephritis(LN)and to explore potential target Chinese medicines,which can provide new directions for clinical treatment of LN.Methods:Gene expres-sion profile microarray dataset of LN was downloaded from GEO database,differential expressed genes(DEGs)were screened using R software,and GO and KEGG enrichment analysis were performed on these DEGs.Protein interaction network analysis of DEGs was performed by applying STRING database,key genes were screened by using Cytoscape,core gene expression was validated by Nephro-seq database,and the infiltration and correlation of 22 kinds of immune cells in LN were calculated by CIBERSORT deconvolution algorithm.Finally,herbal prediction of significantly enriched immune-related biological processes and key target genes were performed by Coremine Medical database.Results:A total of 367 LN-related DEGs were obtained,of which 253 were up-regulated and 114 were down-regulated.GO was mainly enriched in response to viruses,defense response to viruses,regulation of viral life cycle,regulation of viral processes,etc;KEGG was mainly enriched in S.aureus infection,COVID-19,influenza A,complement and coagulation cascade,pertussis,etc.Ten key genes were screened:IFIT3,OAS2,MX1,OAS1,RSAD2,XAF1,ISG15,IFIT1,ITGAM and PTPRC.Immune infiltration by CIBERSORT deconvolution algorithm showed that monocytes and initial B cells were highly expressed in LN,while memory B cells,naive CD4+T cells,follicular helper T cells and resting natural killer cells were lowly expressed in LN.Immune cell correlation analysis showed a positive correlation between initial B cells and plasma cells,a positive correlation between resting natural killer cells and resting dendritic cells,a negative correlation between monocytes and regulatory T cells,and a negative correlation between resting CD4+memory T cells and monocytes.Coremine Medical predicted that Salvia miltiorrhiza,Panax notogin-seng,Scutellaria baicalensis,ginseng,honey,monkey mushroom and peony were found to be most closely related to immunity in LN.Conclusion:The development and progression of LN are results of the combined involvement of multiple genes and pathways.Mono-cytes,memory B cells,initial CD4+T cells and initial B cells are most closely associated with LN.The predicted Salvia miltiorrhiza,Panax notoginseng,Scutellaria baicalensis,ginseng,honey,monkey mushroom and peony may be used as target herbs for the poten-tial treatment of LN.

This article reviews the research advances in the characteristics and application progress of various new models for preclinical cancer research on pancreatic cancer， analyzes and discusses the history， current research status， and advantages and disadvantages of new models of pancreatic cancer， including patient-derived tissue xenograft， conditional reprogramming， and patient derived organoids， and it also reviews the studies that have achieved clinical transformation from preclinical models and proposes possible research prospects in the future.