Tyrosine 23 Phosphorylation of Annexin A2 Promotes Proliferation,Invasion,and Stat3 Phosphorylation in the Nucleus of Human Breast Cancer SK-BR-3 Cells

Objective To investigate the role of tyrosine 23(Tyr23) phosphorylation of Annexin A2(Anxa2) in regulating the proliferation and invasion of human breast cancer SK-BR-3 cells. Methods A panel of lentivirus plasmids expressing Anxa2-wide type(Ana2-WT),Anxa2-Y23A,and Anxa2-Y23D was generated and infected with SK-BR-3 cells.The monoclonal strains were screened.The expression of Anxa2-WT,Anxa2-Y23A,and Anxa2-Y23D was determined by Western blot analysis.The ability of the cells to proliferate was detected through an MTT[3-(4,5-Dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide]test.Boyden chamber assays were employed to examine migration and invasion abilities. The interaction between Anxa2 and Stat3 was analyzed by immunoprecipitation analyses.Nucleoprotein and cytosolic protein were extracted from SK-BR-3,Anxa2-WT,Anxa2-Y23A,and Anxa2-Y23D cells to analyze the expression and localization of Stat3 phosphorylation. Results The monoclonal strains constitutively expressing Anxa2-WT,Anxa2-Y23A,and Anxa2-Y23D were screened.Both Anxa2-W and Anxa2-Y23D enhanced the proliferation,migration and invasion abilities of SK-BR-3 cells(P<0.05).Immunoprecipitation analy revealed that Anxa2 and Stat3 interacted with each other,and the expression of Stat3 phosphorylation in the nucleus was enhanced Anxa2-Y23D. Conclusions Tyr23 phosphorylation of Anxa2 promotes the proliferation and invasion of human breast cancer SK-BR-3 cells and phosphorylation of Stat3 in the nucleus.

Lung-protective Ventilation in Patients with Brain Injury： A Multicenter Cross-sectional Study and Questionnaire Survey in China

Background： Over the years, the mechanical ventilation （MV） strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation （LPV）, among brain-injured patients in China. Methods： This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units （ICUs） across China. Mechanically ventilated patients （18 years and older） with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. Results： A total of 104 patients were enrolled in the present study, 87 （83.7%） of whom were identified with severe brain injury based on a Glasgow Coma Scale 〈8 points. Synchronized intermittent mandatory ventilation （SIMV） was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg （interquartile range [IQR], 7.0-8.9 ml/kg） of the predicted body weight; 50 （48.1%） patients received LPV. The median positive end-expiratory pressure （PEEP） was set to 5 cmH20 （IQR, 5-5 cmH20）. No PEEP values were higher than 10 cmH20. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. Conclusions： Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV.