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Objective:To investigate the synergistic effects and molecular mechanisms of dihydroartemisinin(DHA) and sorafenib(SOR) in inducing ferroptosis in anaplastic thyroid cancer(ATC) cells.Methods:CCK-8 and flow cytometry assays were performed to detect the effects of DHA and SOR on the proliferation and ferroptosis of ATC cells(CAL-62). Real-time fluorescence quantitative PCR and Western blotting assays were performed to detect the expressions of ferroptosis-related genes glutathione peroxidase 4(GPX4), solute carrier family 7 member 11 gene(SCL7A11), lipoxygenase-15(LOX-15), and p53. The levels of iron death intermediate metabolites including lactate dehydrogenase(LDH), glutathione(GSH), malondialdehyde(MDA), ferrous ion(Fe 2+ ), nitric oxide(NO), and reactive oxygen species(ROS)were measured by corresponding assay kits. The corresponding inhibition of DHA and SOR on ATC in vivo was analyzed in a tumor model in nude mice. Results:Compared with the control group, DHA, SOR, and DHA+ SOR treatment significantly inhibited cell proliferation and apoptosis in a dose-dependent manner( P<0.001), with increased LDH, Fe 2+, MDA, and ROS contents and reduced GSH activity( P<0.001), which were promoted by ferrous sulfate(FeSO 4)and reversed by ferroptosis inhibitor-1. Compared with the control group and the drug monotherapy group, 15-LOX-2 and p53 expressions were upregulated in DHA+ SOR group while GPX4 and SCL7A11 expressions were decreased( P<0.001), without significant difference in 15-LOX-1 protein content. In addition, NO level was significantly increased in DHA+ SOR group( P<0.001). DHA and SOR inhibited tumor growth of ATC in vivo. Conclusion:DHA and SOR synergistically induced ferroptosis via upregulating the expression of 15-LOX-2 gene and inhibiting NO synthesis in ATC cells.
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Objective To systematic review the efficacy of Bifidobacterium preparation in Helicobacter pylori ( HP ) eradication therapy. Methods We systematically reviewed clinical research about the efficacy of probiotics in Helicobacter pylori eradication in multiple data-base( PubMed, EMBASE, Medline, OVID, Web of Science); After screening and assessing the quality of the data, we used RevMan 5.3.5 software and Stata 12.0 software for data analysis, then we used GRADE pro3.6.1 software assessing the quality of results.Results Six studies were included with 1396 patients,there were 690 patients in experimental group and 706 patients in control group.Compared with control group, the eradication rates calculated by per-protocol analysis [RR=1.19,95%CI(1.12,1.26),Z=5.87 (P<0.00001)]and intention-to-treat analysis[RR=1.18,95%CI(1.07,1.31),Z=3.33(P=0.0009)]in experimental group was higher,the number of diarrhea[RR=0.43,95%CI(0.23,0.79),Z=2.73(P=0.006)]/the number of nausea[RR=0.67,95%CI(0.56,0.81),Z=4.19 (P<0.0001)]/the number of taste disorders[RR=0.61,95%CI(0.32,1.13),Z=1.57(P=0.12)]in experimental group was lower.The quality of results:the eradication rates calculated by per-protocol analysis was high quality, intention-to-treat analysis and the number of nausea and the number of diarrhea was moderate quality,the number of taste disorders was low quality.Egger’s test showed there was no evidence of substantial publication bias.Conclusion Bifidobacterium preparations during standard triple HP therapy may improve the eradication rate and reduce adverse reactions.
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Objective To investigate the characteristics,treatment and prognosis of the gastrointes-tinal iatrogenic perforation resulting from endoscopic operations.Methods The clinical data of the 107 pa-tients with gastrointestinal iatrogenic perforations caused by endoscopic operations from October 2003 to Octo-ber 2013 were retrospectively studied,and the characteristics,treatment and prognosis of these patients were analysed.Results The incidence of the gastrointestinal iatrogenic perforation resulting from endoscopic oper-ations was 0.041%(107 /263 549,among which 0.006% was diagnostic(13 /232 011),and 0.298% was therapeutic (94 /31 538).A total of 107 patients with gastrointestinal iatrogenic chose conservative medical management,endoscopic clipping or surgery according to different conditions after perforations.All patients had good prognosis.Conclusion Endoscopic therapeutic operations are more likely to lead to the occurrence of iatrogenic gastrointestinal perforations compared with diagnostic operations.And most patients could get good prognosis as long as the appropriate treatment is performed when the perforation occurs.