Objective To explore the anti-intestinal fibrosis mechanism of Dahuang Zhechong pill.Methods Based on the network pharmacology method,the traditional Chinese medicine systems pharmacology database and analysis platform,SwissTargetPrediction database and metabolomics technology was used.OmicsNet 2.0 platform combined with the findings of network pharmacology and metabolomics,and molecular simulation docking and molecular biology methods were used to study the mechanism of anti-intestinal fibrosis of Dahuang Zhechong pill.Results Dahuang Zhechong pill contains 142 potential active ingredients and 855 anti-intestinal fibrosis targets.The 10 core ingredients(quercetin,acacetin,oroxylin a,kaempferol,moslosooflavone,panicolin,etc.)may play a role in regulating lipid metabolism and atherosclerosis,EGFR tyrosine kinase inhibitor resistance,HIF-1 signaling pathway,TNF signaling pathway and IL-17 signaling pathway.Metabolomics results showed that 59 endogenous substances(oxaloacetic acid,ethylthioisonicamide,6-benzylaminopurine,tyrosine and cortisol,etc.)may be the key metabolites of this drug against intestinal fibrosis.Central carbon metabolism,TCA cycle and amino acid metabolism were the key mechanisms,EGFR,AKT1,MAPK1,PTPN11,CASP3,PPARG,MET and PDGFRB may be the core targets.Dahuang Zhechong pill could significantly improve the levels of colorectal edema,inflammatory factors,inflammatory cell infiltration,collagen fiber deposition and α-SMA expression in mice with intestinal fibrosis,reduce the expression levels of pro-inflammatory factors IL-17 and IL-23 in serum,and increase the level of anti-inflammatory factor IL-10.Molecular dynamics simulations demonstrated stable conformational binding between core active ingredients and key targets.Conclusion Dahuang Zhechong pill may regulate EGFR/AKT1/MAPK mediated metabolism-inflammation interaction network through flavonoid components,and can improve intestinal fibrosis in multiple dimensions through molecular validation.

Objective To explore the anti-intestinal fibrosis mechanism of Dahuang Zhechong pill.Methods Based on the network pharmacology method,the traditional Chinese medicine systems pharmacology database and analysis platform,SwissTargetPrediction database and metabolomics technology was used.OmicsNet 2.0 platform combined with the findings of network pharmacology and metabolomics,and molecular simulation docking and molecular biology methods were used to study the mechanism of anti-intestinal fibrosis of Dahuang Zhechong pill.Results Dahuang Zhechong pill contains 142 potential active ingredients and 855 anti-intestinal fibrosis targets.The 10 core ingredients(quercetin,acacetin,oroxylin a,kaempferol,moslosooflavone,panicolin,etc.)may play a role in regulating lipid metabolism and atherosclerosis,EGFR tyrosine kinase inhibitor resistance,HIF-1 signaling pathway,TNF signaling pathway and IL-17 signaling pathway.Metabolomics results showed that 59 endogenous substances(oxaloacetic acid,ethylthioisonicamide,6-benzylaminopurine,tyrosine and cortisol,etc.)may be the key metabolites of this drug against intestinal fibrosis.Central carbon metabolism,TCA cycle and amino acid metabolism were the key mechanisms,EGFR,AKT1,MAPK1,PTPN11,CASP3,PPARG,MET and PDGFRB may be the core targets.Dahuang Zhechong pill could significantly improve the levels of colorectal edema,inflammatory factors,inflammatory cell infiltration,collagen fiber deposition and α-SMA expression in mice with intestinal fibrosis,reduce the expression levels of pro-inflammatory factors IL-17 and IL-23 in serum,and increase the level of anti-inflammatory factor IL-10.Molecular dynamics simulations demonstrated stable conformational binding between core active ingredients and key targets.Conclusion Dahuang Zhechong pill may regulate EGFR/AKT1/MAPK mediated metabolism-inflammation interaction network through flavonoid components,and can improve intestinal fibrosis in multiple dimensions through molecular validation.

Objective To identify mutations in the OSMR gene in a pedigree with familial primary cutaneous amyloidosis (FPCA).Methods Clinical data were collected from a pedigree with FPCA.Peripheral blood samples were obtained from the proband,his 19 relatives,and 50 unrelated healthy human controls.Genomic DNA was extracted from these blood samples,and subjected to PCR for the amplification of 18 encoding exons and their flanking sequences of the OSMR gene followed by DNA sequencing.Results A heterozygous missense mutation c.2081C ＞ T,which leads to the substitution of proline by threonine at position 694,was detected in the OSMR gene of the proband and his affected relatives,but not in unaffected relatives or healthy controls.Conclusion The heterozygous mutation p.P694L in the OSMR gene may cause the clinical phenotype of FPCA in this family.