Background Episodic memory impairment is the core clinical feature of patients with typical Alzheimer's disease (AD) at an early stage. Since sleep plays a very important role in memory consolidation, the relationship between memory impairment and sleep disorders in AD patients is worthy of investigation. Objective To investigate sleep disturbances and their correlations with memory impairment in patients with AD and amnestic mild cognitive impairment (aMCI). Methods Forty-three patients with AD, 43 patients with aMCI, and 43 cognitively unimpaired controls (CUCs) were recruited and subjected to memory assessment via the Hopkins Verbal Learning Test–Revised and objective sleep evaluation via polysomnography (PSG). Results The total sleep time and the percentages of nonrapid eye movement (NREM) sleep stage 3 (N3) and the rapid eye movement (REM) were lower, while the percentages of NREM sleep stage 2 (N2) were greater in the AD and aMCI groups than in the CUC group (all p < 0.01). Compared with the CUC group, the AD group also presented a longer sleep latency and higher NREM sleep stage 1 (N1) percentage, apnea-hypopnea index (AHI), periodic limb movements during sleep index (PLMSI), and arousal index (AI). Both total learning scores and delayed recall scores were positively correlated with the N3 sleep percentage and negatively correlated with the AHI and PLMSI (all p < 0.01). Recognition scores were positively correlated with the N3 sleep percentage and negatively correlated with the AI (all p < 0.01). Conclusions Our results suggest that sleep disturbance is correlated with learning and memory disability in AD and aMCI patients. PSG is useful for screening and monitoring AD.

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.

Iron overload is associated with brain edema in the context of intracerebral hemorrhage (ICH). Here, we investigated the role of histone deacetylase 1 (HDAC1) in mediating oxidative damage induced by iron overload after ICH. Utilizing ICH mouse models and FeCl 2 -induced HT-22 cell models, we assessed HDAC1 expression and its impact on iron overload and oxidative damage. We examined the levels of Kruppel like factor 4 (KLF4), RAN binding protein 9 (RANBP9), as well as the acetylation levels of HDAC1 and histones H3 and H4 in the KLF4 promoter, and the KLF4 level in the RANBP9 promoter. Additionally, we investigated the binding relationships between KLF4 and the RANBP9 promoter, HDAC1 and miR-129-5p. Our results demonstrated elevated HDAC1 expression in ICH mice and FeCl 2 -induced HT-22 cells. HDAC1 silencing improved neurological function in mice, reduced brain edema, and alleviated iron overload and oxidative damage in vitro. HDAC1 downregulated KLF4 expression by reducing acetylation levels in the KLF4 promoter, leading to decreased KLF4 enrichment in the RANBP9 promoter and increased RANBP9 expression. Furthermore, upstream miR-129-5p inhibited HDAC1, and the downregulation of miR-129-5p mitigated the protective effect of HDAC1 silencing. Collectively, our findings highlight the significant role of HDAC1 in exacerbating iron overload-induced oxidative damage following ICH and its regulation by miR-129-5p.

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 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.

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.

睡眠和免疫可相互作用,免疫系统激活可影响睡眠,而睡眠又可影响机体防御的固有免疫和获得性免疫.睡眠障碍可对免疫系统产生有害后果,不仅能增加心脑血管疾病、糖尿病、肿瘤等疾病的风险,也会诱发神经免疫性疾病的恶化,并导致各种原因的死亡.现就睡眠与免疫的相关性研究进展进行介绍.

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.

Sleep deprivation negatively influences all aspects of health. Oxidative stress and inflammatory responses induced by sleep deprivation participate in its adverse effects but the regulatory mechanisms to counteract them remain poorly understood. In mice subjected to sleep deprivation for 7 days, we found activation of microglia and astrocyte accompanied by down-regulation of α7 nicotinic acetylcholine receptor (α7-nAChR) and reduced activation of downstream PI3K/AKT/GSK-3β. These changes occurred with an increase of pro-inflammatory factors, together with reduced levels of anti-inflammatory factors, transcriptor Nrf-2, and anti-oxidant enzyme HO-1. Administration of an α7-nAChR agonist PHA-543613 induced activation of PI3K/AKT/GSK-3β, and reversed changes in pro-inflammatory and anti-inflammatory factors, Nrf-2 and HO-1. These results suggest that stimulation of α7-nAChR reduce neuroinflammation and oxidative stress after chronic sleep deprivation.

目的 探讨慢性睡眠剥夺对小鼠海马组织α7-nAChR表达及星形胶质细胞和小胶质细胞表面α7-nAChR的表达的影响.方法 成年C57BL/6J小鼠随机分为3组:正常对照(control,CC)组、慢性睡眠剥夺(sleepdeprivation,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印迹、实时荧光定量PCR分别检测各组小鼠海马组织α7-nAChR蛋白及基因的表达;使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.结果 SD组与CC组比较,SD组海马组织的α7-nAChR蛋白表达、mRNA表达和星形胶质细胞表面α7-nAChR的表达均明显低于CC组(P=0.001,P=0.038,P=0.003);SD组与SD+PHA-543613组比较,SD+PHA-543613组海马组织的α7-nAChR蛋白表达、mRNA表达和星形胶质细胞表面α7-nAChR的表达较SD组升高(P=0.037,P=0.002,P=0.027).结论 慢性睡眠剥夺不仅抑制海马组织α7-nAChR基因及蛋白的表达,同时降低α7-nAChR在星形胶质细胞表面的表达,海马组织胶质细胞α7-nAChR的减少可能是慢性睡眠剥夺后认知功能下降的危险因素.

Objective To evaluate the neuropsychological performance of RBD patients and its correlations with ob-jective sleep parameters. Methods Twenty-two RBD patients diagnosed by video-polysomnography( v-PSG) in neurology clinic of TianJin Medical University General Hospital and Twenty-three healthy gender,age and education-level matched subjects were enrolled. Subjects underwent neuropsychological tests,including mini-mental state examination(MMSE),Au-ditory verbal learning test(AVLT),Rey Complex Figure Test(RCFT),Clock Drawing Test(CDT),Symbol digit modalities test(SDMT),Trail Making Test A and B(TMT A and TMT B),Stroop test A,B and C,Animal fluency test(AFT),City flu-ency test(CFT),Animal-City fluency test,Boston naming test(BNT). Neuropsychological performance and objective sleep parameters were compared between the two groups,correlations between neuropsychological performance and objective sleep parameters in RBD group were analysed. Results Compared with the control group, RBD patients performed worse in MMSE,immediate memory,short and long delay recall of AVLT,time of RCFT,TMT A,TMT B,Stroop A,Stroop B,Stroop C with significant difference(P<0. 05);the mean percentage of NREM-I sleep increased,NREN-II and NREM-III sleep decreased,periodic leg movement index increased in RBD patients. Furthermore,lower sleep efficiency was correlated with decreased SDMT score(r=0. 491,P=0. 020),CFT score(r=0. 436,P=0. 043) and more time of TMT A(r= -0. 654,P=0. 001),lower total sleep time was correlated with less RCFT and BNT score(r=0. 600,P=0. 003;r =0. 482,P =0. 023),more time of TMT A(r= -0. 573,P=0. 005) in RBD patients. Conclusions RBD patients exhibited declined cognition,impaired multi-domain neuropsychological performance including vebral learning memory,exeuctive and visuospa-tial ability,disturbed objective sleep architecture,increased periodic leg movement index. Decreased total sleep time and sleep efficiency may contribute to neuropsychological performance deterioration in RBD patients.

Sleep deprivation impairs hippocampal neurogenesis, but the underlying mechanisms are inadequately understood. Sleep deprivation is associated with an increased production of pro -inflammatory factors. In this study, we demonstrate that acute rapid eye movement (REM) sleep deprivation in mice for 3 days leads to increased expression of interleukin (IL)-17A, IL-17F and activation of p38 MAPK pathway in the hippocampus, together with suppressed cell proliferation in the dentate gyrus. Similarly, activation of p38 MAPK and suppressed cell proliferation in the dentate gyrus were observed after administration of recombinant IL-17 in mice without sleep deprivation. Pharmacological blockade of the p38 MAPK after sleep deprivation mitigates sleep deprivation induced ablation of cell proliferation in the dentate gyrus with unaltered expression of IL-17A and IL-17F. In addition, hippocampal neural progenitor cells express IL-17 receptor A (IL-17RA) and IL-17 receptor C (IL17RC). These findings suggest that acute REM sleep deprivation suppresses proliferation of adult hippocampal neural progenitor cells by a mechanism involving IL-17 and p38 MAPK signaling.

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.