Objective To explore the biological mechanisms of isorhamnetin(ISO)inhibition of breast cancer(BC)progression and effects on paclitaxel sensitivity by in vivo and in vitro experiments.Methods The effects of ISO on MDA-MB-231 cell viability,migration,invasion and apoptosis were explored by CCK-8,scratch,Transwell invasion and apoptosis assays.ISO biological functions were analyzed and core target genes were identified by genome-wide microarrays,functional enrichment and protein-protein interactions(PPI).CYP1B1 expression characterization and prognosis in BC were assessed by quantitative Real-time polymerase chain reaction(qRT-PCR),Western blotting(WB),and Kaplan-Meier plotter database.The effects of CYP1B1 overexpression on MDA-MB-231 cell viability,migration,invasion and apoptosis were explored by CCK-8,scratch,Transwell invasion and apoptosis assays.The effects of ISO and CYP1B1 on BC tumor growth were analyzed by establishing a subcutaneous graft tumor animal model and verified by histological analysis with immunohistochemistry(IHC)and hematoxylin and eosin(HE)staining.The effects of ISO and CYP1B1 on NF-κB signaling were analyzed by qRT-PCR and WB.The effect of ISO combined with paclitaxel on BC progression was analyzed by in vitro and in vivo experiments.Results The results of CCK-8 assay showed that ISO inhibited the viability of MDA-MB-231 cells with an IC50 value of 11.93 μmol/L;the scratch,Transwell invasion and apoptosis assays confirmed that ISO inhibited the migration and invasion of MDA-MB-231 cells and promoted apoptosis(P＜0.05).Volcano plot showed a total of 80 differentially expressed genes(DEGs),of which ISO promoted the expression of 27 genes and inhibited the expression of 53 genes.Gene set enrichment analyses showed that DEGs were mainly enriched in the signaling of organic hydroxyl compound metabolic process,inflammatory response,sterol metabolic process,and nuclear factor-κB(NF-κB).qRT-PCR,WB,and Kaplan-Meier plotter results showed that CYP1B1 mRNA and protein expression was increased in BC and mediated worse prognosis(P＜0.05).CCK-8,scratch,Transwell invasion and apoptosis assays showed that CYP1B1 overexpression enhanced MDA-MB-231 cell viability,migration and invasion,and inhibited apoptosis,which was reversed by the addition of ISO(P＜0.05).The results of in vivo experiments showed that ISO downregulated CYP1B1 expression and attenuated NF-κB signaling(P＜0.05).The results of in vitro and in vivo experiments showed that ISO combined with paclitaxel significantly inhibited BC cell viability and tumor growth(P＜0.05).Conclusion ISO inhibits BC malignant biological behavior by modulating the CYP1B1/NF-κB signaling axis,and ISO enhances paclitaxel sensitivity.

Objective To explore the biological mechanisms of isorhamnetin(ISO)inhibition of breast cancer(BC)progression and effects on paclitaxel sensitivity by in vivo and in vitro experiments.Methods The effects of ISO on MDA-MB-231 cell viability,migration,invasion and apoptosis were explored by CCK-8,scratch,Transwell invasion and apoptosis assays.ISO biological functions were analyzed and core target genes were identified by genome-wide microarrays,functional enrichment and protein-protein interactions(PPI).CYP1B1 expression characterization and prognosis in BC were assessed by quantitative Real-time polymerase chain reaction(qRT-PCR),Western blotting(WB),and Kaplan-Meier plotter database.The effects of CYP1B1 overexpression on MDA-MB-231 cell viability,migration,invasion and apoptosis were explored by CCK-8,scratch,Transwell invasion and apoptosis assays.The effects of ISO and CYP1B1 on BC tumor growth were analyzed by establishing a subcutaneous graft tumor animal model and verified by histological analysis with immunohistochemistry(IHC)and hematoxylin and eosin(HE)staining.The effects of ISO and CYP1B1 on NF-κB signaling were analyzed by qRT-PCR and WB.The effect of ISO combined with paclitaxel on BC progression was analyzed by in vitro and in vivo experiments.Results The results of CCK-8 assay showed that ISO inhibited the viability of MDA-MB-231 cells with an IC50 value of 11.93 μmol/L;the scratch,Transwell invasion and apoptosis assays confirmed that ISO inhibited the migration and invasion of MDA-MB-231 cells and promoted apoptosis(P＜0.05).Volcano plot showed a total of 80 differentially expressed genes(DEGs),of which ISO promoted the expression of 27 genes and inhibited the expression of 53 genes.Gene set enrichment analyses showed that DEGs were mainly enriched in the signaling of organic hydroxyl compound metabolic process,inflammatory response,sterol metabolic process,and nuclear factor-κB(NF-κB).qRT-PCR,WB,and Kaplan-Meier plotter results showed that CYP1B1 mRNA and protein expression was increased in BC and mediated worse prognosis(P＜0.05).CCK-8,scratch,Transwell invasion and apoptosis assays showed that CYP1B1 overexpression enhanced MDA-MB-231 cell viability,migration and invasion,and inhibited apoptosis,which was reversed by the addition of ISO(P＜0.05).The results of in vivo experiments showed that ISO downregulated CYP1B1 expression and attenuated NF-κB signaling(P＜0.05).The results of in vitro and in vivo experiments showed that ISO combined with paclitaxel significantly inhibited BC cell viability and tumor growth(P＜0.05).Conclusion ISO inhibits BC malignant biological behavior by modulating the CYP1B1/NF-κB signaling axis,and ISO enhances paclitaxel sensitivity.

Objective To investigate the effects of laparoscopic and open resection with pelvic autonomic nerve preservation (PANP) on sexual function of male patients with lower rectal cancer. Methods Total 177 male patients with lower rectal cancer received surgery from September 2008 to December 2013 were enrolled into two groups: the laparoscopic PANP group (n = 105) and the open PANP group (n = 72). The classifications of erectile and ejaculatory functions were used to evaluate the sexual functions of patients at 6 months and 12 months post-operation, respectively. The effect of different operation on the sexual function of the male patients was compared between the two groups. Results The incidence rates of erectile dysfunction at 6 months and 12 months post-operation in the laparoscopic group were lower than those in the laparotomy group (P < 0.05). The incidence rates of ejaculatory dysfunction at 6 months and 12 months post-operation in the laparoscopic group were also lower than those in the laparotomy group (P < 0.05). Conclusion The laparoscopic resection with PANP in patients with lower rectal cancer can not only clearly reveal pelvic autonomic nerve and effectively protect them, but also reduce the incidence of postoperative sexual dysfunction.

Objective Matrix metalloproteinase-10 (MMP-10) has been shown to be highly associated with atherosclerosis.Recent studies showed that levels of MMP-10 were elevated in infarcted tissues in acute ischemic stoke.However,serum levels of MMP-10 in patients with acute ischemic stroke have never been studied previously.This study aims to investigate the serum levels of MMP-10 in patients with acute ischemic stroke,and evaluate the association of serum levels of MMP-10 with stroke subtypes based on Trial of Org 10 172 in acute stroke treatment classifications,the severity of stroke,risk factors and carotid artery plaque.Methods The circulating levels of MMP-10 were measured by enzyme linked immunosorbent assay in 194 subjects,including 109 patients who were diagnosed as acute ischemic stroke in the Department of Neurology,Shengjing Hospital,China Medical University from April to December 2012,and the 85 healthy controls.Results Patients with acute ischemic stroke had higher serum levels of MMP-10 compared with healthy controls (6.59 (6.07,7.31) μg/L vs 5.16 (3.87,5.94) μg/L,Z =8.33,P ＜ 0.01).NIHSS score had positive correlation with serum levels of MMP-10 (r =0.204,P =0.037).Classified by risk factors,we compared the MMP-10 levels of subsets,and results displayed that statistically significant difference existed between dyslipidemia subset and non-dyslipidemia subset (Z =2.07,P =0.042).MMP-10 levels had positive correlation with serum levels of LDL-cholesterol (r =0.248,P =0.040),but negative correlation with thrombin-activatable fibrinolysis inhibitor (TAFI;r =-0.208,P =0.030).The subset with unstable plaques had higher MMP-10 levels than that with stable plaque (6.62 (6.13,7.36) μg/L) vs 6.10 (6.00,6.46) μg/L,Z =2.12,P =0.034),implying the relationship of MMP-10 and atherosclerosis.Conclusions Patients with acute ischemic stroke have higher serum levels of MMP-10 compared with the healthy controls,and MMP-10 levels have positive correlation with the severity of stroke.MMP-10 is associated with the subtypes of stroke classified by risk factors,and dyslipidemia subset has higher levels of MMP-10 than that of non-dyslipidemia subset.MMP-10 has positive correlation with LDL-cholesterol,but negative correlation with TAFI.MMP-10 may be involved in the process of formation and disruption of unstable plaques,which contribute to the stenosis of arteries and onset of acute ischemic stroke.