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A b s t r a c tIntroduction: Histone deacetylase inhibitors (HDACIs) inhibit human osteosarcoma growth and cause apoptosis. Previously, we reported that HDACIs induce autophagy via the FOXO1 pathway. Whether there is involvement of autophagy in anti-osteosarcoma activity of HDACIs is still unknown. Material and methods: Confocal microscopy was performed to determine the formation of GFP-LC3 puncta. Western blotting was conducted to measure FOXO1, and autophagy-related protein levels. Small interference RNA (siRNA) specific for FOXO1 was transfected into U2OS cells to knock down FOXO1 expression level. Flow cytometry was performed to quantify cell death. Results: In this study, we first observed that trichostatin A (TSA) induces autophagy in human osteosarcoma cells. Moreover, we found that TSA treatment inhibits the mammalian target of rapamycin (mTOR) signaling pathway and enhances forkhead box O1 (FOXO1) transcriptional activity, which is responsible for the increased autophagy level, while suppression of FOXO1 function by siRNA knockdown markedly decreases TSA-induced autophagy. Conclusions: We found that inhibition of autophagy, either by autophagy inhibitors or ATG gene knockdown, markedly enhances TSA-caused cell death. Taken together, our studies reveal the function of autophagy in HDACI-caused osteosarcoma cell death and thus support the development of a novel therapeutic strategy by combining HDACIs and autophagy inhibitors in osteosarcoma treatment.
Hyperuricemia is a strong and independent predictor of all-cause mortality
in cardiovascular disease and has been found to play a role in diseases exacerbated
by oxidative stress and inflammation. This study aimed to evaluate whether
serum uric acid (UA) level is an indicator of outcome in patients with acute
paraquat poisoning. A total of 205 subjects who had attempted suicide by oral
ingestion of paraquat were admitted to the emergency room between January
2009 and June 2014. Initial serum UA level and other laboratory parameters
were measured. A total of 66 patients died during the 30 days after admission,
corresponding to a 32.2% cumulative incidence of mortality. UA levels were
higher in non-survivors than survivors (P < 0.001) and 30-day mortality
increased with increasing baseline serum UA level (P < 0.001). In
a prediction analysis for 30-day mortality, the serum UA level had a cut-off
concentration of 284 µmol/L in female patients and 352 µmol/L
in male patients. Multivariate Cox proportional hazards regression analyses
showed that white blood cell counts and UA were independent prognostic factors.
In conclusion, we showed that serum UA may be an independent predictor of
30-day mortality in patients with paraquat poisoning.
Background: Triage decision making is crucial for patients arrived at emergency room as it influences the clinical outcome. Appropriate standard to discriminate patients into different category is challenging. We introduced a suitable emergency preview triage pain model for quality management methods through the pain assessment module. Methods: The pain quality control and management of emergency pre-examination triage were realized by designing the pain assessment module of the intelligent triage system. Clinical nurses completed the assessment of pain score and PQRST pain content through the pain tool in the pain assessment module of the intelligent triage system. The computer system would automatically assess the triage category according to the pain score. Triage nurses determined the priority of emergency care based on the type of care.Results: The pain quality control target monitoring reached 95% of the target management value in ten months. There were two months when the target management value was not reached 95%, June 2019 (94.28%), and December 2019 (94.28%), respectively, slightly lower than the target management value (95%).
Conclusions:The application of the pain quality control management mode of emergency preexamination triage unifies the standards of emergency pre-examination triage pain, standardizes the pain assessment and improves the level of emergency pre-examination triage pain management.
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