Erythropoietin (EPO), supports the function and survival of neurons through astrocytes and has a protective role in neonatal asphyxia brain injury; yet, its mechanism of action remains unclear. As a neuroprotective factor, EPO is also used in the treatment of various diseases, such as neurodegenerative diseases, Parkinson's disease, traumatic brain injury, by decreasing inflammatory reaction, resisting apoptosis, and lowering oxidative stress. The aim of this study was to examine the effect and mechanism of EPO on promoting human brain glial cell proliferation under hypoxia in vitro. Under CoC1 2 -induced hypoxia, after adding EPO, high-throughput sequencing was used to screen out meaningful up-regulated and significant differentially expressed genes PI3K, IKKα CDK1 related to proliferation, and make further verification by qPCR and western blotting. Under hypoxia, EPO promoted cell proliferation and the expression of PI3K while this effect was inhibited (along with a decrease of downstream genes IKKα and CDK1 decreased) after adding PI3K inhibitor to cell culture. EPO can promote cell proliferation and CDK1 expression, while after inhibiting CDK1 expression, the promotion of EPO on cell proliferation was eliminated. These data proved that EPO promotes the proliferation of U251 cells by activating the PI3K-IKKα-CDK1 signaling pathway under CoC1 2 -induced hypoxia.

Background The accuracy of total calcium and its corrected value for predicting critically high and critically low ionized calcium in critical illness is controversial. The aim of this study was to investigate whether the concentration of total serum calcium, either corrected for albumin or not, could predict critically high or low values in critical illness. Methods This report describes a retrospective study using the Medical Information Mart for Intensive Care (MIMIC) III database. Test panels that contained serum albumin, total calcium, and ionized calcium (named ATI panels) with order time intervals of less than one hour were extracted. The predictive accuracy of total calcium, either corrected for albumin or not, was assessed using receiver operating characteristic (ROC) curve analysis. Results A total of 12 118 ATIs with 103 critically low and 92 critically high ionized calcium results were extracted. The areas under ROC curves (AUCs) of corrected and uncorrected total calcium for predicting critically low ionized calcium were 0.69 (95% CI: 0.61‐0.76) and 0.70 (95% CI: 0.63‐0.78), respectively. For predicting critically high ionized calcium, the AUCs were 0.98 (95% CI: 0.97‐1.00) and 0.97 (95% CI: 0.95‐1.00), respectively. With positive predictive values (PPVs) of 0.05 and 0.10, the sensitivities (both corrected and uncorrected) were approximately 0.50 for predicting critically low ionized calcium and 0.95 for predicting critically high ionized calcium. Conclusions Total calcium, either corrected for albumin or not, is not a reliable test to predict critically low ionized calcium in critical illness. Total calcium's predictive accuracy for critically high ionized calcium is high.

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