Background Recent years, survival rates of human with high-risk acute myeloid leukaemia (AML) have not raised substantially. This research aimed to investigate the role of 4′-O-Methylbroussochalcone B, for the treatment of human AML. Methods Firstly, we evaluated the effects of six chalcones on AML cells activity by MTT assay. Immunofluorescence staining, tubulin polymerization assay and N,N′-ethylenebis (iodoacetamide) (EBI) competition assay were performed on ML-2 cells. Transwell and apoptosis assay were also utilized in ML-2 cells and OCI-AML5 cells. The expressions of migration-related proteins, apoptosis-related proteins and Wnt/β-catenin pathway were detected by Western Blot. Results The results found six chalcones exhibited the anti-proliferative activity against different AML cell lines. Based on the results of immunofluorescence staining, tubulin polymerization assay and EBI competition assay, 4′-O-Methylbroussochalcone B was discovered to be a novel colchicine site tubulin polymerization inhibitor. 4′-O-Methylbroussochalcone B could induce apoptosis, inhibit proliferation and migration of ML-2 cells and OCI-AML5 cells. The cells were arrested in the G2-M phase by the treatment of 4′-O-Methylbroussochalcone B. In addition, 4′-O-Methylbroussochalcone B regulated MAPK and Wnt/β-catenin pathways in AML cells. Conclusion 4′-O-Methylbroussochalcone B might inhibit proliferation and migration of the AML cells by MAPK and Wnt/β-catenin pathways as a tubulin polymerization inhibitor. It is promising for 4′-O-Methylbroussochalcone B to become a new drug to treat AML.
ObjectivesIn the early stage of sepsis, identifying high-risk paediatric patients with a poor prognosis and providing timely and adequate treatment are critical. This study aimed to evaluate the effect of average body temperature within 24 hours of admission on the short-term prognosis of paediatric patients with sepsis.DesignA retrospective cohort study.SettingA single-centre, tertiary care hospital in China, containing patient data from 2010 to 2018.Participants1144 patients with sepsis were included.InterventionNone.Primary and secondary outcome measuresThe main outcome measure was in-hospital mortality, which was defined as death from any cause during hospitalisation. The secondary outcome was the length of hospital stay.ResultsThe LOWESS method showed a roughly ‘U’-shaped relationship between body temperature on the first day and in-hospital mortality. Multivariate logistic regression showed that severe hypothermia (OR 14.72, 95% CI 4.84 to 44.75), mild hypothermia (OR 3.71, 95% CI 1.26 to 10.90), mild hyperthermia (OR 3.41, 95% CI 1.17 to 9.90) and severe hyperthermia (OR 5.15, 95% CI 1.84 to 14.43) were independent risk factors for in-hospital mortality. Compared with other variables, the Wald χ2value of temperature on the first day minus the degree of freedom was the highest.ConclusionsWhether hypothermic or hyperthermic, the more abnormal the temperature on the first day is, the higher the risk of in-hospital death in children with sepsis.
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