Purpose: To evaluate the correlation between sleep microstructure, autonomic nervous system activity, and neuropsychological characteristics in chronic insomnia (CI) patients with obstructive sleep apnea (OSA).Patients and Methods: Forty-five CI-OSA patients, forty-six CI patients and twenty-two matched healthy control subjects (HCs) were enrolled. CI-OSA patients were then divided into two groups: mild OSA and moderate-to-severe OSA. All participants completed neuropsychological tests, which included the Hamilton Depression and Anxiety Scales (HAMD and HAMA), the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), the Epworth Sleepiness Scale (ESS), and the Mini-mental State Examination (MMSE). The autonomic nervous system activity and sleep microstructure were examined by the PSM-100A.Results: The CI-OSA patients exhibited higher scores on the PSQI, ESS, ISI, HAMA, and HAMD than HCs and CI patients (all p < 0.01). The CI-OSA patients had a lower proportion of stable sleep, REM sleep and a higher proportion of unstable sleep ratio (all p < 0.01) than HCs and CI patients (all p < 0.01). The CI-OSA patients had higher ratios of LF and LF/HF, and lower ratios of HF and Pnn50% (all p < 0.01) than HCs and CI patients (all p < 0.01). Compared to CI-mild OSA patients, the CI-moderate-to-severe OSA patients presented with a higher ESS scores, higher ratios of LF and LF/HF, and lower ratios of HF (all p < 0.05). In CI-OSA patients, higher HAMD scores were correlated with decreased MMSE scores (r=-0.678, p < 0.01). A higher LF ratio was correlated with higher HAMD and HAMA scores (r=0.321, p=0.031, r =0.449, p =0.002), and a higher HF ratio was correlated with lower HAMD and HAMA scores (r=-0.321, P =0.031, r =-0.449, p =0.002).Conclusion: OSA exacerbates the abnormalities of sleep microstructure and the autonomic nervous dysfunction in CI patients. Dysfunction of the autonomic nervous system could contribute to mood deterioration in CI with OSA patients.

Purpose: The present study aimed to explore the effectiveness of virtual reality (VR) therapy on sleep quality and associated symptoms, such as depression and anxiety, cognitive decline and autonomic nervous dysfunction, in chronic insomnia patients. Methods: Sixty-three chronic insomnia patients were randomly divided into VR group (n = 32) and control group (n = 20) based on a standard drug therapy. Patients were instructed to use VR at home once a day at evening for 6-week treatment. All participants received evaluations of subjective sleep quality measured with the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), and the Epworth Sleepiness Scale (ESS), depression and anxiety symptoms measured with the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA), cognitive function, and objective sleep structure and autonomic nerve function examination measured with the sleep respiration monitoring device at baseline and after 6-week treatment. The main objective of this study was sleep quality assessment as the primary outcome. Results: After 6-week treatment, the decreases in PSQI score (-5.60 f 2.37 vs -4.10 f 1.80, P = 0.020) and ISI score (-8.81 f 4.52 vs -6.35 f 2.89, P = 0.038) of the VR group were significantly greater compared with the control group. The VR group showed more reduction in HAMD score (-9.96 f 4.41 vs -7.50 f 2.89, P = 0.035) and HAMA score (-8.96 f 3.80 vs -6.80 f 3.22, P = 0.046), and more increase in processing speed (0.54 f 0.60 vs 0.00 f 0.79, P = 0.011) than the control group. Moreover, the low-frequency coupling (-10.00 f 17.40 vs. 8.25 f 20.03, P = 0.001) was lowered and the high-frequency coupling (9.99 f 17.40 vs. -8.24 f 20.03, P = 0.001) was elevated in the VR group relative to the control group. Conclusion: Our findings offered preliminary evidence that VR therapy enhanced sleep quality and also lessened depressive and anxious symptoms, and improved cognitive and autonomic functioning in patients with chronic insomnia.

OBJECTIVE:To determine the clinical markers based on cognitive and motor profiles in predicting phenoconverion and phenotype in isolated rapid eye movement sleep behavior disorder (iRBD). METHODS:45 iRBD patients and 25 healthy controls were included in the follow-up study. All participates received comprehensive evaluations of cognitive, motor and autonomic function at baseline. Positive phenoconversion were identified according to standard diagnostic criteria during follow-up. RESULTS:21 iRBD patients displayed phenoconversion in a mean follow-up of 2.9 ± 1.6 years, with 14 presenting motor phenotype and 7 cognitive phenotype. In iRBD, visuospatial, memory, attention-executive function, information processing speed, and motor function predicted phenoconversion, with the combination of Trail Making Test (TMT) and Alternate-tap Test (ATT) performing best (sensitivity = 95.0 %, specificity = 75.0 %); attention-executive function, information processing speed, and motor function predicted motor phenotype conversion, with the combination of TMT and ATT performing best (sensitivity = 100 %, specificity = 66.7 %); visuospatial, memory, and attention-executive function predicted cognitive phenotype conversion, with TMT performing best (sensitivity = 83.3 %, specificity = 91.7 %). Furthermore, individuals with lower z-scores of TMT, Symbol Digit Modalities Test, and ATT than the established cutoff values in iRBD exhibited a significantly higher risk for phenoconversion at follow-up (HR = 2.98, 9.53, 11.68; respectively). CONCLUSIONS:In iRBD, the attention-executive and motor function served as optimum combined markers in predicting phenoconversion and motor phenotype, whereas the attention-executive function performed best in predicting cognitive phenotype. Poor attention-executive function, information processing speed and motor function in iRBD independently increased the risk of phenoconversion.

To investigate the positive impact of e-aid cognitive behavioural therapy on the sleep quality, anxiety, and depression of nurses on site during the COVID-19 pandemic. Nurses on site at the Tianjin Medical University General Hospital Airport Site experiencing insomnia, anxiety and depression during the COVID-19 prevention and control period, from February 2020 to April 2021, were selected and divided into either an e-aid cognitive behavioural therapy (eCBT-I) group or a control group using a randomized grouping method. The eCBT-I group was given standard eCBT-I for 6 weeks; the control group did not get any intervention. The Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI) were used to evaluate the sleep quality of the subjects. The Generalized Anxiety Disorder 7-item (GAD-7) and the Patient Health Questionnaire (PHQ-9) were used to assess the subjects’ anxiety and depression. Changes in sleep quality, anxiety and depression before and after treatment were compared between the two groups. Of 118 nurses randomized, the PSQI and ISI scores within the eCBT-I group (n=60) were significantly lower after treatment (5.9 ± 3.9, 6.7 ± 4.5) than before treatment (10.4 ± 3.5, 12.4 ± 4.7) (p <0.05). Compared to the scores of the control group (n=58) (9.1 ± 3.9, 10.6 ± 4.1), the PSQI and ISI scores in the eCBT-I group (5.9 ± 3.9, 6.7 ± 4.5) were lower after treatment (p <0.05). The GAD-7 and PHQ-9 scores in the eCBT-I group were all lower after treatment (3.7±3.4, 4.2±4.1) than before treatment (6.7±4.9, 7.7±5.1) (p <0.05). Compared with subjects in the control group (7.1±5.6, 7.3±5.1), subjects in the eCBT-I group (3.7±3.4, 4.2±4.1) had lower scores on the GAD-7 and PHQ-9 scales after treatment (p <0.05). eCBT-I improved the sleep quality of frontline nurses during the COVID-19 prevention and control period and relieved anxiety and depression.

Sleep deprivation negatively influences cognition, however, the regulatory mechanisms to counteract this effect have not been identified. IGF-1 has been shown to be anti-inflammatory and neuroprotective in CNS injury models. In this study, we determined the impact of IGF-1 on brain injury and inflammation while modeling sleep deprivation. We found that IGF-1 was downregulated in human peripheral blood and in mice subjected to sleep deprivation for 5 days, with reduced activation of the downstream PI3K/AKT/GSK-3β pathway in mice brains. In addition, we found reduced levels of the anti-apoptosis enzyme Bcl-2 and increased levels of pro-apoptosis enzyme Caspase-9 expression, together with increased pro-inflammatory factors. The administration of IGF-1 after sleep deprivation induced activation of the PI3K/AKT/GSK-3β pathway, reversed changes in Bcl-2, Caspase-9, and pro-inflammatory factors, and alleviated cognitive impairment. Notably, IGF-1 also induced activation of the PI3K/AKT/GSK-3β pathway, and displayed anti-apoptosis and anti-inflammatory properties under normal sleep conditions,while IGF-1 did not improve the cognition under normal sleep conditions. These results suggest that the IGF-1/PI3K/AKT/GSK-3β pathway is involved in the regulation of cognitive function after sleep deprivation through modulation of apoptosis and inflammatory response. IGF-1 could be a viable therapeutic target, though further investigation is required to better understand its role in sleep deprivation.

昼夜节律失调性睡眠-觉醒障碍(circadian rhythm sleep-wake disorders,CRSWDs)是指昼夜时间维持与诱导系统变化或内源性昼夜节律与外部环境间不同步所引起的各种睡眠觉醒障碍,其最常见症状是入睡困难、维持睡眠困难及日间睡眠增多.据估计,多达10％的成人睡眠障碍患者可能患有CRSWDs[1].CRSWDs可诱发抑郁焦虑情绪和认知功能改变.重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)是一种安全、无创、无疼痛的生物刺激技术,近年来临床研究发现治疗睡眠障碍的疗效确切.临床中对睡眠质量的评估通常基于主观的患者自我陈述、心理评估和访谈,多导睡眠图(polysomnography,PSG)虽高度精确,但其检查过程复杂、不舒服和价格昂贵令大量人群不易接受,近年来由美国哈佛医学院动态生医指标中心研发的心肺耦合技术(cardiopulmonary coupling,CPC),作为一种便携式睡眠检测技术被广泛应用于睡眠相关疾病的监测与分析,具有区分和客观量化睡眠质量的功能[2].既往研究多关注于用PSG监测的睡眠参数评估rTMS治疗失眠的疗效,而对CRSWDs患者应用rTMS治疗的研究较少.我们旨在观察rTMS治疗对CRSWDs患者睡眠微结构及睡眠稳定性、睡眠质量、抑郁焦虑情绪及认知功能变化的影响,为CRSWDs患者的rTMS治疗提供更多的临床证据.

目的 观察α7-nAChR/PI3K/AKT/GSK-3β通路在慢性睡眠剥夺后的保护作用,并探讨其作用机制.方法 成年C57BL/6J小鼠随机分为3组:对照(CC)组、慢性睡眠剥夺(SD)组、慢性睡眠剥夺后腹腔注射α7-nAChR激动剂-PHA-543613(SD+PHA-543613)组.采用Western-blot印迹检测各组小鼠海马组织α7-nAChR及p-AKT、p-GSK-3β、Nrf-2、HO-1蛋白表达变化;使用实时荧光定量PCR检测各组小鼠海马组织α7-nAChR mRNA水平及炎性因子与抑炎因子TNF-α、IL-1β、IFN-γ、MCP-1、Arg-1、CD206、TGF-β、YM-1mRNA表达水平;采用免疫荧光染色法观察各组小鼠海马组织星形胶质细胞、小胶质细胞表面α7-nAChR的表达变化;通过水迷宫评估小鼠的行为学.结果 慢性睡眠剥夺7 d后,SD组海马组织的α7-nAChR蛋白、mRNA的表达明显低于CC组(P=0.001,P=0.038),SD组海马组织p-AKT蛋白表达显著低于CC组(P=0.019),p-GSK-3β 蛋白表达量高于CC组(P=0.011);慢性睡眠剥夺后腹腔注射α7-nAChR激动剂-PHA-543613后海马组织星形胶质细胞表面α7-nAChR的表达高于SD组(P=0.027),p-AKT、p-GSK-3β 的蛋白表达也明显高于SD组(P=0.047,P=0.017);腹腔注射 α7-nAChR激动剂-PHA-543613后,SD+PHA-543613组海马组织Nrf-2、HO-1蛋白表达量和抑炎因子CD206、TGF-β的mRNA表达量与SD组相比明显增多(P=0.020,P=0.016,P<0.01,P<0.01),而促炎因子TNF-α、MCP-1的mR-NA表达量与SD组相比显著下降(均P<0.01).腹腔注射α7-nAChR激动剂-PHA-543613后小鼠的逃避潜伏期与SD组相比缩短,处于目标象限时间延长、穿越平台次数增多(P=0.000,P=0.000,P=0.001).结论 慢性睡眠剥夺后刺激α7-nAChR通过激活PI3K/AKT/GSK-3β减轻神经炎症和氧化应激.

AbstractObjectivesTo assess the correlation of cognitive function with sleep stability and depressive‐anxious symptoms in insomnia patients.MethodsTwenty‐two insomnia patients with cognitive impairment (insomnia‐CI), 21 insomnia patients with normal cognition (insomnia‐CN), and 15 matched healthy control subjects (HCs) were enrolled and completed neuropsychological tests, the Hamilton Depression and Anxiety Scales (HAMD and HAMA), the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index (PSQI),the Insomnia Severity Index (ISI), and the cardiopulmonary coupling (CPC) examination. Ratios of high‐frequency coupling (HFC), low‐frequency coupling (LFC), and very low‐frequency coupling (VLFC) measured by CPC analysis represent stable sleep, unstable sleep, and wake/rapid eye movement (REM) sleep, respectively.ResultsThe HAMD, HAMA, PSQI, and ISI scores were higher in the insomnia‐CN patients than in the HCs (all p < .01). However, no differences were found in the HFC, LFC, and VLFC ratio between the HCs and insomnia‐CN groups. Compared with the insomnia‐CN patients, insomnia‐CI patients exhibited higher scores on the HAMD, HAMA (all p < .01), and PSQI (p < .05), performed worse on the Auditory Verbal Learning Test, Trial Making Test B, and Stroop Test B (all p < .01), had a lower HFC ratio, and had a higher LFC ratio in the CPC analysis (all p < .01). Furthermore, in the insomnia patients, poorer cognition was correlated with a decreased HFC ratio and an increased VLFC ratio (r = .356, p = .019; r = −.339, p =.026, respectively) and increased HAMD and HAMA scores (r = −.507, p < .001; r = −.561, p < .001, respectively); a higher VLFC ratio was correlated with an increased ISI score (r = .346, p = .023).ConclusionsCognitive deterioration in insomnia patients was associated with a decreased stable sleep ratio, an increased wake/REM sleep ratio and more severe symptoms of depression and anxiety. CPC analysis can reflect the severity of insomnia.

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.

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.

胰岛素样生长因子-1(Insulin-ike growth factor 1,IGF-1)是一个7. 5 kDa的肽类激素,它主要在肝脏产生,受垂体分泌的生长激素调节. IGF-1在神经的形成和发育过程中起到重要作用.大部分脑内IGF-1 被认为是在低密度脂蛋白受体相关蛋白 1 ( LRP1 )和低密度脂蛋白受体相关蛋白 2 (LRP2)分子的帮助下从血浆中通过血脑屏障转运而来的[1] .海马的IGF-1水平与血清中IGF-1水平明显相关,提高血清中IGF-1,海马中IGF-1水平也会相应升高[2] . IGF-1主要与IGF-1受体( IGF-1R)结合引起胞内底物的募集及磷酸化,两者结合后IGF-1R活化,并且通过RAS\MEK\ERK通路使级联系统启动,同时通过PI3K\AKT\mTOR信号通路促进细胞生长并且抑制细胞凋亡,从而起到神经保护作用,这种神经保护作用可以出现在多种细胞内[3] .神经系统变性病是一组慢性进行性神经损害的疾病总称,可能与神经组织在分化、发育、成熟、衰老等过程中出现分子生物学障碍有关,包括阿尔茨海默病( Alzheimer disease, AD)、帕金森病(Parkinson disease,PD)、肌萎缩侧索硬化( Amyotrophic lateral aclerosis,ALS)、脊肌萎缩症(Spinal muscular atrophy,SMA)、亨廷顿舞蹈病( Huntington disease,HD)等.本文就IGF-1在不同神经系统变性病中的作用进行综述.