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Objective:To explore the effect of virtual reality (VR) on sleep quality, sleep structure and neuropsychological characteristics of patients with chronic insomnia.Methods:Fifty one patients with chronic insomnia enrolled from Department of Neurology, General Hospital of Tianjin Medical University from October 2021 to April 2022 were chosen; according to their wills, they were divided into VR combined drug treatment group ( n=26) and drug treatment group ( n=25). Patients in drug treatment group accepted non-benzodiazepine combined with melatonin receptor agonist and serotonin reuptake inhibitor; in patients of VR combined drug treatment group, VR was added 30 min/d for 5 d/week on basis of above drug therapy. Subjective sleep quality was assessed by Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Insomnia Severity Scale (ISI). Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) were used to assess anxiety and depression. Mini-Mental State Examination (MMSE), Auditory Verbal Learning Test (AVLT), Digital Span Test (DST), Trail Making Test (TMT), Stroop Color Word Test A/B/C, Judgment of Line Orientation Test (JLO), and Symbol Digit Modalities Test (SDMT) were used to assess the overall and individual cognitive functions. Portable sleep monitor (PSM)-100A based on cardiopulmonary coupling technology was used to evaluate the sleep structure. Differences of subjective sleep quality, sleep structure, and neuropsychological characteristics were compared between the 2 groups before and after treatment and in VR combined drug treatment group before and after treatment. Results:(1) After 6 weeks of treatment, compared with the drug treatment group, the VR combined with drug treatment group had significantly decreased scores of PSQI, ISI, HAMD and HAMA, increased total scores of AVLT immediate memory, scores of AVLT short delay recall, long delay recall and recognition, higher SDMT scores, increased correct times of DST reciting in reverse order, shorter time in TMT-A and TMT-B, higher proportion of high frequency coupled sleep (HF, stable sleep), lower proportion of low frequency coupled sleep (LF, unstable sleep), and decreased LF/HF ( P<0.05). (2) The VR combined with drug treatment group after VR treatment had significantly decreased PSQI, ISI, HAMD and HAMA scores, higher total scores of AVLT immediate memory, higher scores of AVLT short delay recall, long delay recall and recognition, shorter time in TMT-A and TMT-B, increased correct times of DST reciting in order and reciting in reverse order, and higher scores of JLO, Stroop Color Word Test A/B/C and SDMT, higher proportion of HF sleep, lower LF sleep, decreased LF/HF, and decreased arousal frequency compared with that before VR treatment ( P<0.05). Conclusion:VR combined with drug treatment can effectively improve the subjective sleep quality and sleep structure, reduce depression and anxiety, and improve memory and attention of patients with chronic insomnia.
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@#Objective Investigated the influences of chronic sleep deprivation on the expression α7-nAChR and the activity of its downstream PI3K/AKT/GSK-3β pathway in neuroglia in mice.Methods Adult C57BL/6J mice aged 7-8 weeks were randomly divided into three groups，control（CC）group，chronic sleep deprivation（SD） group，chronic sleep deprivation + intraperitoneal injection α7-nAChR agonists PHA-543613（SD + PHA - 543613） group.The protein expression of α7 -nAChR,p-AKT,p-GSK-3β,Nrf-2,HO-1 in mice hippocampus were examined by Western Blot，the gene expression of α7 -nAChR and the gene expression of TNF-α,IL-1β,IFN-γ,MCP-1,Arg-1,CD206,TGF-β,YM-1 were examined by Rt-PCR；the expression of α7-nAChR on astrocytes and microglias in mice hippocampus were assesed by double-labeled immunofluorescence.Spatial learning and memory was assessed by morris water maze （MWM） test.Results After chronic sleep deprivation for 7 days，the expression of α7-nAChR protein，mRNA in SD group decreased significantly when compared with CC group（P=0.001,P=0.038）;the expression of protein p-AKT decreased in SD group compared with CC group（P=0.019）,while the expression of protein p-GSK-3β increased in SD group compared with CC group（P=0.011）.Afterα7-nAChR agonists PHA-543613 treatment,the expression of α-7 nAChR on astrocytes increased significantly when compared with SD group（P=0.027，the expression of p-AKT and p-GSK-3βincreased when compared with SD group（P=0.047,P=0.017.At the same time，the expression of Nrf-2，HO-1 and anti-inflammatory factors（CD206，TGF-β）increased significantly compared with SD group（P=0.020,P=0.016，P<0.01,P<0.01），while the expression of inflammatory factors（TNF-α，MCP-1） decreased compared with SD group（P<0.01）.After α7-nAChR agonists PHA-543613 treatment，the escape latency at the end of experiment was decreased，the frequency of crossing platforms and the time in the target quadrant was prolonged compared to the SD group（P=0.000,P=0.000,P=0.001）.Conclusion Stimulation of α7-nAChR reduces inflammation and oxidative stress via activation of PI3K/AKT /GSK-3β after chronic sleep deprivation.
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Objective:To explore the effects of IGF-1 on cognitive function in REM sleep deprivation model mice and its possible mechanism.Methods:C57BL/6J mice aged 8 weeks were randomly divided into 4 groups with 6 mice in each group.They were Normal control group (CC group), REM sleep deprivation 5d group (SD group), REM sleep deprivation 5d+ Intraperitoneal injection of IGF-1 group (SD+ IGF-1 group), and REM sleep deprivation 5d+ Intraperitoneal injection of PBS group (SD+ PBS group). The Morris water maze was used to test the cognitive function of all mice.The content of IGF-1 in mice hippocampus was detected by Elisa, and the expression level of TNF-α, IL-1β and IL-6 mRNA in mice in hippocampus was determined by RT-qPCR.Western blot was used to detect the protein expression levels of p-GSK3β, GSK3 beta, p-Akt, Akt, Bcl-2 and Caspase-9 in mice hippocampus of each group.Results:The time in the target quadrant and the number of times across the platform of the SD group ((11.87±1.67)s, (12.50±5.54) times, respectively)was lower than that of the CC group((19.40±1.75)s, (22.17±8.21) times, respectively), the difference was statistically significant( t=8.71, 2.26, both P<0.05). The time in the target quadrant and the number of times across the platform of the SD+ IGF-1 group ((18.11±1.12)s, (21.83±10.26) times), which were higher than those in the SD+ PBS group ((10.60±1.36)s, (11.50±3.94) times). The difference was statistically significant( t=8.69, 2.42, both P<0.05). The expression of IGF-1 protein in the hippocampus of SD group ((579.38±55.95) pg/mg) was lower than that of CC group ((729.13±79.46)pg/mg), and the difference was statistically significant ( t=3.83, P<0.05). The expression of IGF1 protein in the hippocampus of SD+ IGF-1 group((665.50±55.21)pg/mg) was significantly higher than that of SD+ PBS group ((563.40±76.33)pg/mg), the difference was statistically significant ( t=2.61, P<0.05). The expression of p-GSK3 beta protein (1.51±0.02) in mice hippocampus of SD group was higher than that of CC group (1.47±0.03), and the expression of p-Akt (0.92±0.04) was lower than that of CC group (1.18±0.05), The difference was statistically significant ( t=3.07, t=10.85, both P<0.05). The expression of Caspase-9 in mice hippocampus of SD group(0.65±0.03)was higher than that of CC group (0.60±0.02). The expression of Bcl-2 in mice hippocampus of SD group (0.93±0.03) was lower than that of CC group (1.00±0.04), and the difference was statistically significant ( t=3.65, 3.98, both P<0.05). The expression of p-Akt and p-GSK3β protein in mice hippocamps of SD+ IGF-1 group( (1.20±0.04), (1.57±0.03)) was increased compared with those of SD+ PBS group ((0.92±0.05), (1.51±0.03)), and the difference was statistically significant ( t=3.98, 11.49, both P<0.05). The expression of Caspase-9 in mice hippocamps of SD+ IGF-1 group (0.60±0.03) was decreased compared with that of SD+ PBS group (0.67±0.02). The expression of Bcl-2 in mice hippocampus of SD+ IGF-1 group (1.00±0.03) was increased compared with SD+ PBS group (0.93±0.02), and the difference was statistically significant ( t=5.19, 3.83, both P<0.05). The expression level of TNF-α, IL-1β, and IL-6 mRNA in mice hippocampus of SD group ((3.36±0.67), (2.00±0.40), (4.63±0.72)) were increased compared with CC group with statistically significant differences ( t=8.58, 6.15, 2.37, all P<0.05). The expression level of TNF-α, IL-1β, and IL-6 mRNA in mice hippocampu of SD+ IGF-1 group ((1.21±0.25), (1.08±0.33), (0.98±0.47)) were lower than those of SD+ PBS group ((3.86±0.79), (2.11±0.30), (4.43±0.67)), with statistically significant differences ( t=7.81, 5.76, 10.39, all P<0.05). Conclusion:The cognitive function of mice decreased after REM sleep deprivation and improved after IGF-1 supplementation, which may be related to the activation of PI3K / Akt signal pathway by IGF-1, thus reducing apoptosis related signal transduction and inflammatory factor expression.
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Objective:To analyze the characteristics of gamma oscillation in chronic insomnia patients with anxiety and depression, and to investigate its underlying neural mechanism.Methods:According to the anxiety and depression scores, the subjects with chronic insomnia who met the diagnostic criteria were divided into chronic insomnia with anxiety and depression group ( n=19) and chronic insomnia group ( n=13). Healthy subjects matched with age, gender, and educational background were selected as the normal control group ( n=16). The EEGs from the three groups under resting state and cognitive load state were collected.The relative gamma power was then calculated by fast Fourier transform.The spatial distribution pattern of the gamma oscillation in the three groups was analyzed.Spearman correlation analysis was employed to quantify the correlation between relative gamma powers and sleep scale, anxiety and depression scale scores. Results:In the resting state, the relative gamma power in the chronic insomnia with anxiety and depression, chronic insomnia and normal control group was 0.192 1±0.008 0, 0.210 3±0.009 6, 0.237 3±0.006 4, respectively.In the cognitive load state, the relative gamma power in the three groups increased compared with those in the resting state (0.220 7±0.008 1, 0.249 5±0.009 8, 0.267 7±0.007 2, respectively) (all P<0.05). In the resting state, the relative gamma power (F3, F4, C3, C4, P3, P4, O2, F8, T4) in the chronic insomnia with anxiety and depression group (0.179 9±0.009 7) and the chronic insomnia group (0.194 4±0.010 4) was lower than that in control (0.236 0±0.012 0, P<0.05). In the cognitive load state, the relative gamma power (F3, C3, C4, P3, P4, T4) in the chronic insomnia with anxiety and depression group (0.207 3±0.009 7) was lower than that in control (0.259 1±0.009 4)( P<0.05). There was a significant negative correlation between the relative gamma power in the nodes(F3, C3, P3)and the insomnia, anxiety and depression in the three groups(correlation coefficient r=-0.467--0.274, P<0.05). Conclusion:Chronic insomnia patients with anxiety and depression are often accompanied by cognitive dysfunction.The loss of gamma oscillation in left posterior, left central and left apex may be one of the potential neural mechanisms of cognitive dysfunction in chronic insomnia patients with anxiety and depression.
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Objective To evaluate the objective sleep status of patients with chronic insomnia by cardiopulmonary coupling (CPC) technique, and evaluate the characteristics of cognitive dysfunction to explore the correlation between objective sleep and cognitive dysfunction in patients with chronic insomnia. Methods Forty-three patients with chronic insomnia, admitted to our hospital from October 2017 to April 2019, were enrolled in our study;15 age-, gender-and education-matched healthy volunteers were recruited as control group. All subjects followed their daily routine at home and completed CPC examination. Montreal Cognitive Assessment (MoCA), Auditory Vocabulary Learning Test (AVLT), Trail Making Test (TMT) and Stroop Color Word Test were used to evaluate the general and single cognitive functions, respectively. The correlation of objective sleep with cognitive function was analyzed. Results (1) As compared with those in the control group, high frequency coupling (stable sleep) ratio was significantly decreased, low frequency coupling (un-stable sleep) ratio and extremely low frequency coupling (rapid-eye-movement sleep/waking) ratio were significantly increased, and latency of high frequency coupling was significantly prolonged in chronic insomnia group (P<0.05). (2) Chronic insomnia group had significantly lower MoCA total scores than control group (P<0.05), specifically manifested as decrement of visuospatial ability and execution and attention abilities; specific cognitive test showed that chronic insomnia group performed worse in immediate recall, and had delayed recall of AVLT, longer time consumption in TMT-B, smaller number of wired arrival numbers, and longer time consumption in Stroop color word test than the control group, with significant differences (P<0.05). (3) There was a correlation between CPC sleep structure and Cognitive Function Scale scores in patients with chronic insomnia. Conclusion In patients with chronic insomnia, stable sleep is reduced, un-stable sleep and rapid-eye-movement sleep/waking are increased; the impaired cognition domains are visual space and executive function, attention and memory; disturbed sleep structure aggravates the memory and execution impairment of patients with chronic insomnia.
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Objective To investigate the effects of continuous positive airway pressure (CPAP) on sleep status,neuropsychological characteristics in patients with stroke combined with obstructive sleep apnea syndrome (OSAHS).Methods Fifty-four patients hospitalized with stroke in Tianjin Medical University General Hospital from May 2014 to January 2016,who were with snoring and met the OSAHS diagnostic criteria,were randomly divided into CPAP combined with drug treatment group (25 cases) and drug treatment alone group (29 cases).The sleep structure and respiratory parameters were evaluated by polysomnography,and the changes of the patients' sleep status was assessed by Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI).The changes of neurocognitive function were assessed by Montreal Cognitive Assessment (MoCA),Digital Span Test (DST) and Hopkins Verbal Learning Testrevised (HVLT),and Patient Health Questionnaire-9 (PHQ9) was used to evaluate the depression mood changes.The changes of sleep status,cognitive function and mood in the CPAP combined with drug treatment group were compared before and three months after CPAP combined with drug treatment,and with the drug treatment alone group.Results Because five cases were dropped off,there were 20 patients in the CPAP combined with drug treatment group and 29 patients in the drug treatment alone group who completed the study.After three months of CPAP combined with drug treatment,the respiratory parameters apnea hypopnea index (AHI) in the CPAP combined with drug treatment group (29.32 ± 16.57) was significantly lower than that before treatment (41.66 ± 21.84;t =3.926,P =0.001),and the minimum blood oxygen saturation (LSaO2;82.11％ ± 5.66％) was significantly higher than that before treatment (76.11％ ± 8.90％;t=-5.054,P=0.000).However,the sleep structure parameters did not show statistically significant changes compared with those before treatment.The ESS,PSQI and PHQ9 scores in the CPAP combined with drug treatment group (4.53 ± 3.86,3.00 ± 2.45,0.00 (0.00,2.00)) were significantly decreased compared with those before treatment (10.58 ± 7.82,7.53 ± 2.87,3.00 (1.00,9.00);t =-3.883,P =0.001;t =-6.522,P =0.000;Z =-3.549,P =0.000),whereas MoCA,HVLT (total scores,recall and recognition) and DST 1,2 scores in the CPAP combined with drug treatment group (23.37 ± 4.75,22.32 ± 6.90,7.47 ± 3.82,7.84 ± 2.59,5.32 ± 2.81) were increased compared with those before treatment (22.16±4.94,19.16 ±7.66,6.68 ±3.74,7.32 ±2.67,5.00 ±3.00;t=-2.773,P=0.013;t=-6.857,P=0.000;t=-2.704,P=0.015;t=-2.249,P=0.037;t=-2.882,P =0.010).The ESS,PSQI and PHQ9 scores were significantly reduced in the CPAP combined with drug treatment group compared with the drug treatment alone group (8.76 ± 6.92,7.59 ± 5.49,5.00 (2.50,9.50);t=-2.711,P=0.009;t=-3.941,P=0.000;Z=-4.555,P=0.000),whereas the DST1 score was significantly increased compared with the drug treatment alone group (6.45 ± 1.43;t =2.144,P =0.042).Conclusions Three-month CPAP combined with drugs mainly improved the daytime sleepiness and depression of patients with stroke combined with OSAHS.Cognition especially in attention was significantly improved,and the degree of low ventilation and hypoxia was alleviated,whereas there was no significant change in sleep structure disorder.