Objective:To explore the relationship between gut microbiota and giant cell arteritis (GCA), and to identifyits potential therapeutic strategies.Methods:Gut microbiota data were obtained from the MiBioGen consortium genome-wide association study (GWAS), and GCA data were obtained from the FinnGen consortium public GWAS. Causal associations between gut microbiota and GCA were assessed using two-sample Mendelian randomization (MR) analyses, including inverse-variance weighted (IVW), weighted median, MR-Egger regression, simple mode, and weighted mode methods. Heterogeneity and horizontal pleiotropy were evaluated, and false positive results were excluded by using the Benjamini-Hochberg (BH) method of multiple hypothesis testing. All analyses were completed using the TwoSampleMR and MRPRESSO software packages (version 4.3.0) in R language. The analysis of the intestinal flora data, followed by conducting network pharmacology analysis were carried out by Cytoscape 3.9.1 and perform molecular docking verification was performed with AutoDock Vina software.Results:IVW simulations revealed 13 gut microbiota taxa were associated with GCA, of which Lachnospiraceae was significantly negatively associated with GCA risk[nSNP=16, OR(95% CI)=0.32(0.16, 0.63), β=-1.15, Se=0.35, P=0.001, FDR<0.05], and there was no heterogeneity (Cochran′s Q test, Q=13.42, P=0.490) as well as horizontal pleiotropy ( P=0.370). Further literature search and computer simulation docking analysis showed that genistein binds to MMP2 with a binding energy of -43.1 kJ/mol. Conclusion:Lachnospiraceae in the gut microbiota was is negatively associated with GCA, and genistein may be able to regulate the abundance of Lachnospiraceae through the MMP2 target to treat GCA, providing a new therapeutic approach for giant cell arteritis.

Objective:To explore the relationship between gut microbiota and giant cell arteritis (GCA), and to identifyits potential therapeutic strategies.Methods:Gut microbiota data were obtained from the MiBioGen consortium genome-wide association study (GWAS), and GCA data were obtained from the FinnGen consortium public GWAS. Causal associations between gut microbiota and GCA were assessed using two-sample Mendelian randomization (MR) analyses, including inverse-variance weighted (IVW), weighted median, MR-Egger regression, simple mode, and weighted mode methods. Heterogeneity and horizontal pleiotropy were evaluated, and false positive results were excluded by using the Benjamini-Hochberg (BH) method of multiple hypothesis testing. All analyses were completed using the TwoSampleMR and MRPRESSO software packages (version 4.3.0) in R language. The analysis of the intestinal flora data, followed by conducting network pharmacology analysis were carried out by Cytoscape 3.9.1 and perform molecular docking verification was performed with AutoDock Vina software.Results:IVW simulations revealed 13 gut microbiota taxa were associated with GCA, of which Lachnospiraceae was significantly negatively associated with GCA risk[nSNP=16, OR(95% CI)=0.32(0.16, 0.63), β=-1.15, Se=0.35, P=0.001, FDR<0.05], and there was no heterogeneity (Cochran′s Q test, Q=13.42, P=0.490) as well as horizontal pleiotropy ( P=0.370). Further literature search and computer simulation docking analysis showed that genistein binds to MMP2 with a binding energy of -43.1 kJ/mol. Conclusion:Lachnospiraceae in the gut microbiota was is negatively associated with GCA, and genistein may be able to regulate the abundance of Lachnospiraceae through the MMP2 target to treat GCA, providing a new therapeutic approach for giant cell arteritis.

Objective To explore the relationship of molecular biology characteristic and the treatment outcome,and influence factors of neoadjuvant chemotherapy (NAC) in inflammatory breast cancer (IBC).Methods The clinicopathological data of 103 IBC patients who were treated with NAC from January 2005 to June 2013 were analyzed retrospectively.Immunohistochemical method was used to detect the expression of estrogen receptor (ER),progesteron receptor (PR),human epidermal growth factor receptor 2 (HER-2) and E-cadherin.The treatment outcome were evaluated.Results In 103 IBC patients,ER negative was 48 patients,PR negative was 51 patients,HER-2 positive was 45 patients,E-cadherin positive was 66 patients.The effective rate of chemotherapy was 72.8％ (75/103).The effective rate of chemotherapy in taxane-based group was significantly higher than that in anthracycline-based group [80.6％ (50/62) vs.61.0％(25/41)],and there was significant difference (P ＜ 0.05).The effective rate of chemotherapy in ER,PR,E-cadherin negative patients was significantly higher than that in ER,PR,E-cadherin positive patients [83.3％ (40/48) vs.63.6％ (35/55),82.4％ (42/51) vs.63.5％ (33/52),83.8％ (31/37) vs.66.7％ (44/66)],and there was significant difference (P ＜ 0.05).The effective rate of chemotherapy in taxane-based group with E-cadherin positive patients was significantly higher than that in anthracycline-based group with E-cadherin positive patients [77.5％ (31/40) vs.50.0％ (13/26)] (P ＜0.05).No correlation existed between the expression of HER-2 and the treatment outcome of chemotherapy (P ＞ 0.05).Conclusion ER,PR and E-cadherin negative patients with IBC is chemosensitive to NAC.The positive expression of E-cadherin may be an important factor of chemotherapy resistance.For the patients with E-cadherin positive,taxane-based chemotherapy regimen can achieve a better effective rate.