Sphingosine 1-phosphate receptor 1 regulates bloodbrain barrier permeability in epileptic mice

Destruction of the blood-brain barrier is a critical component of epilepsy pathology.Several studies have demonstrated that sphingosine 1-phosphate receptor 1 contributes to the modulation of vascular integrity.However,its effect on blood-brain barrier permeability in epileptic mice remains unclear.In this study,we prepared pilocarpine-induced status epilepticus models and pentylenetetrazol-induced epilepsy models in C57BL/6 mice.S1P1 expression was increased in the hippocampus after status epilepticus,whereas tight junction protein expression was decreased in epileptic mice compared with controls.Intraperitoneal injection of SEW2871,a specific agonist of sphingosine-1-phosphate receptor 1,decreased the level of tight junction protein in the hippocampus of epileptic mice,increased blood-brain barrier leakage,and aggravated the severity of seizures compared with the control.W146,a specific antagonist of sphingosine-1-phosphate receptor 1,increased the level of tight junction protein,attenuated blood-brain barrier disruption,and reduced seizure severity compared with the control.Furthermore,sphingosine 1-phosphate receptor 1 promoted the generation of interleukin-1βand tumor necrosis factor-αand caused astrocytosis.Disruption of tight junction protein and blood-brain barrier integrity by sphingosine 1-phosphate receptor 1 was reversed by minocycline,a neuroinflammation inhibitor.Behavioral tests revealed that sphingosine 1-phosphate receptor 1 exacerbated epilepsy-associated depression-like behaviors.Additionally,specific knockdown of astrocytic S1P1 inhibited neuroinflammatory responses and attenuated blood-brain barrier leakage,seizure severity,and epilepsy-associated depression-like behaviors.Taken together,our results suggest that astrocytic sphingosine 1-phosphate receptor 1 exacerbates blood-brain barrier disruption in the epileptic brain by promoting neuroinflammation.

Effectiveness of the combination of workshops and flipped classroom model to improve tube fixation training for nursing students

BACKGROUND Tube indwelling is a key procedure in modern medicine.Careful tube setup is necessary to prevent unplanned extubation.The training for tube fixation is timeand resource-consuming,and optimal modes of training are currently being sought.Previous studies have compared workshops and flipped classroom models separately using conventional teaching strategies,but no study has examined a combination of both teaching models in nursing training.AIM To compare the effectiveness of workshops vs workshops combined with the flipped classroom model for improving tube fixation training for nursing students.METHODS This was a prospective cohort study.In this study,149 nurses who joined our hospital in 2019 underwent training using workshops combined with the flipped classroom model(experimental group),while 159 nurses who joined the hospital in 2018 received only workshop-based training(control group).The combination of workshops with the flipped classroom training model was divided into two modules:pre-class and in-class training.The participation of nurses in the training activities,onsite assessment of training,nurses’evaluation of their training,and related indicators of tube quality management were evaluated.RESULTS The average age of nurses in the control group was 22.94±0.94 years and that of nurses in the experimental group was 25.42±3.23 years(P<0.01).The qualified rate of after-class assessments for the experimental and control groups was 100.00%(average score:94.01±2.78 points)and 91.82%(average score:84.24±2.94 points),respectively(P<0.01).Most nurses in the experimental group completely agreed that the combined training was helpful to cultivate clinical thinking and independent learning ability and to master knowledge of tube fixation.In addition,the training content within the pre-class teaching video,pre-class tube atlas,pre-class main instructor guidance,in-class demonstration,and in-class practice was very informative.The experimental group had higher evaluation scores than the control group(4.88±0.38 vs 4.67±0.64;P<0.01).Comparison of tube quality management before and after training in 2018 to 2019 revealed that the unplanned ureteral tube removal rate dropped from 0.25‰to 0.06‰,the unplanned chest tube removal rate dropped from 1.07‰to 0.78‰,and the unplanned gastric tube removal rate dropped from 0.36‰to 0.17‰.The incidence rate of pressure ulcers caused by the tube decreased from 0.78‰to 0.45‰.CONCLUSION The combination of workshop and flipped classroom training is effective in improving tube fixation training of nurses,cultivating nurses’active learning abilities and clinical thinking,and improving the safety of the procedure.