Based on the multitarget-directed ligand strategy, a series of pyridazine derivatives, including 3-benzyloxy-6-arylpyridazines, N-benzyl-6-(2-hydroxyphenyl) pyridazinones and 3-benzylthio-6-(2- hydroxyphenyl) pyridazines, were designed and synthesized. In vitro evaluation revealed that most 3-benzyloxy-6-arylpyridazines displayed potent and selective MAO-B inhibitory activity. Among them, compounds 6l (IC50 = 0.0053 μM, SI > 1904.7) and 6s (IC50 = 0.0031 μM, SI > 3194.8) were identified as the most promising inhibitors, acting via a reversible and competitive mechanism. Additionally, both compounds 6l and 6s demonstrated moderate antioxidant activity and strong chelating ability toward Cu2+. Notably, 6l effectively suppressed Cu2+-induced ROS generation. Further assessments of BBB permeability and aqueous solubility indicated that both 6l and 6s can penetrate the BBB, with 6l exhibiting moderate solubility. In anti-neuroinflammatory assays, 6l significantly inhibited LPS-induced activation of BV-2 cells and reduced the release of inflammatory factors NO、TNF-α and IL-1β. It also reduced LPS-induced intracellular ROS production, and protected SH-SY5Y cells from MPTP+-induced injury. Pharmacokinetics study confirmed that 6l could enter the central nervous system. In an MPTP-induced subacute mouse PD model, high-dose 6l significantly improved behavioral deficits, restored DA content, lowered MDA content, reduce oxidative stress and neuroinflammation. These results demonstrated that compound 6l is a promising multi-target anti-PD agent worthy of further investigation.

Objective: To investigate the pathophysiological characteristics of cerebral blood flow (CBF) in patients with narcolepsy type 1 (NT1) via the arterial spin labeling (ASL) technique. Methods: Thirty patients with diagnostic NT1 (PTs) and 34 age- and sex-matched healthy controls (HCs) were recruited for this study. Basic information was collected, and clinical evaluation and neuroimaging, including ASL and T1-3DBRAVO, was performed. The z-normalized CBF (zCBF) and spatial coefficient of variation (sCoV) were calculated, and the changes in NT1 were compared via analysis of covariate (ANCOVA). Furthermore, spearman's correlation analysis between impaired regional perfusion and clinical features was performed. Age, sex, and normalized grey matter volume were included as covariates. Results: Compared with that of HCs, the zCBF of PTs significantly differed in regions of fronto-temporal-occipital cortex, right insula and posterior insula, and left rostral/dorsal anterior cingulate gyrus (ACG) (P < 0.006). Moreover, the sCoV was significantly altered in the frontotemporal cortex, rostral ACG, right hippocampus, and posterior insula (P < 0.003). In PTs, positive correlations were identified between the zCBF of the right superior/ middle frontal gyrus (SFG/MFG) and mean sleep latency, and between the zCBF of the left SFG of the frontal pole and sleep hallucination severity. Moreover, the sCoV of the right MFG/hippocampus were positively associated with Rapid Eye Movement efficiency and negatively associated with Hamilton Anxiety Scale score, respectively. Conclusion: PTs exhibited abnormal regional perfusion in the frontal-temporal-occipital cortex and limbic system regions, which may serve as patient-specific imaging markers. Alterations in perfusion may lead to the clinical manifestations of underlying psychological and sleep disorders in PTs.

Objective: To explore topological alterations of white matter (WM) structural connectome, and their associations with clinical characteristics in type 1 narcolepsy (NT1). Methods: 46 NT1 patients and 34 age- and sex-matched healthy controls were recruited for clinical data and diffusion tensor imaging collection. Using graph theory analysis, the topology metrics of structural connectome, rich club organization, and connectivity properties were compared between two groups. Furthermore, partial correlation analysis was performed between the network characteristics of 90 nodes or weakened edges and clinical data using Pearson or Spearman correlation, controlling by age and sex. Results: Between-group comparison reflected that NT1 patients exhibited sleep disorders with comorbidities of impaired cognition and psychological problems. In patients, the global efficiency, local efficiency, and average clustering coefficient were significantly lower, whereas characteristic path length was larger compared to healthy control. Pertinently, nodal path length of left middle frontal gyrus was positively correlated with Pittsburgh Sleep Quality Index scores. The rich club analysis identified six affected nodes: bilateral dorsolateral superior frontal gyrus, bilateral supplementary motor area, left hippocampus, and left pallidum. Furthermore, six significantly weakened structural connections seeding from these rich club nodes have shown significant correlations with clinical index or polysomnography parameters. Conclusion: In NT1 patients, WM structural connectome has shown to be disrupted, which were primarily distributed in frontal-parietal cortex, subcortical regions, and particularly cingulate, potentially affecting their clinical manifestations.

Rationale and Objectives: To explore indicators of neuropsychological changes in patients with type 1 narcolepsy (NT1) using restingstate functional magnetic resonance imaging (rs-fMRI). Materials and Methods: Thirty-four NT1 patients and 34 age- and sex-matched healthy volunteers were recruited for neuropsychiatric assessments and rs-fMRI data acquisition. Fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and related brain functional connectivity (FC) were calculated for the two groups and compared using a two-sample t test with cluster-level FDR correction. Moreover, partial correlation analysis was performed between these functional values of changed brain regions and clinical scales. Results: Compared to those of healthy controls, spontaneous functional activities were significantly weakened in patients with NT1 in regions such as the left/right posterior cerebellum lobe, left inferior temporal gyrus, and left dorsolateral superior frontal gyrus, whereas those in regions such as the left middle occipital gyrus, right inferior occipital gyrus, and left/right lingual gyrus were significantly strengthened. Furthermore, NT1 patients displayed significantly changed FCs between the left/right anterior cingulate gyrus (ACG) and regions such as the left/right cerebellum, left middle occipital gyrus, and left inferior frontal gyrus in the operculum. In partial correlation analysis, the functions in the left dorsolateral superior frontal gyrus were significantly related to the Trail Making Tests (TMT) score. Moreover, the FC between the left ACG and left inferior frontal gyrus in the operculum was highly correlated with anxiety and depression features, including the Hamilton Anxiety Scale (HAMA) score and Hamilton Depression Rating Scale (HAMD-17) score. Conclusion: Patients with NT1 exhibited abnormalities in the anterior cingulate cortex, frontal-parietal cortex, hippocampus, and left/ right posterior cerebellum lobe. The deactivation of the left frontal-temporal cortex is stronger, which is involved in the cognitive decline and mental disorders in these patients. Damage to the ACG may affect its FC with other regions and cause cognition and emotion dysregulation, perhaps by impairing patients' visual pathways and frontal-temporal-parietal networks. Hence, these could be important biomarkers for their neuropsychological changes.

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.

Objective:To investigate the possible role and mechanism of purinergic ligand-gated ion channel 7(P2X7)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3) inflammasome pathway in cognitive impairment induced by sleep deprivation (SD)mice.Methods:SPF grade male C57BL / 6J mice aged 6-8 weeks were randomly divided into 3 groups according to the random number table method with 6 mice in each group.They were normal control group (CC group), SD group and SD+ P2X7 receptor antagonist brilliant blue G(BBG) group (SD+ BBG group). Modified multiple platform method was used to establish a 5-day SD model in mice.During the SD intervention period, the mice in SD+ BBG group were injected with BBG(50 mg/kg) intraperitoneally once a day, while the mice in CC group and SD group were injected with the same volume of 0.9% sodium chloride solution.Morris water maze was conducted to evaluate the cognitive function of mice.The protein expression levels of P2X7, NLRP3, caspase-1, apoptosis-associated proteins(ASC) and interleukin-1β(IL-1β) in hippocampus were detected by Western blot.RT-qPCR was used to detect the mRNA expression levels of tumor necrosis factor-α(TNF-α), IL-1β, interleukin-18(IL-18) and microglial polarization surface markers CD206 and CD86 in hippocampus.Graph pad Prism 8.0 software and SPSS 25.0 software were used for statistical analysis and mapping.Results:(1) The interaction effect between time and groups of escape latency in three groups of mice was significant ( F=15.76, P<0.001). From the 2nd to 5th day, the escape latencies of mice in SD group were higher than those of CC group, while the escape latencies of mice in SD+ BBG group were lower than those of SD group (all P<0.05). (2)The results of the space exploration experiment showed that there were statistically significant differences in target quadrant residence time and the times of crossing the platform( F=6.65, P=0.009; F=12.39, P<0.001). The target quadrant residence time ((23.42±0.55) s) and times of crossing the platform ((17.67±0.71) times) of the SD group were both lower than those of the CC group ((29.48±1.78) s, (23.33±0.95) times) (both P<0.05), while the target quadrant residence time ((28.62±1.19) s) and the times of crossing the platforms ((21.33±0.76) times) of the SD+ BBG group were both higher than those of the SD group (both P<0.05). (3)There were statistically significant differences in the protein levels of inflammatory related proteins such as P2X7, NLRP3, caspase-1, ASC and IL-1β in the hippocampus of mice among the 3 groups( F=8.23, 8.97, 8.45, 54.42, 8.12, all P<0.05). Compared with CC group, the protein levels of P2X7 ((0.93±0.02), (0.71±0.04)), NLRP3 ((0.97±0.04), (0.62±0.09)), caspase-1 ((1.00±0.03), (0.76±0.07)), ASC ((0.96±0.02), (0.77±0.04)) and IL-1β ((0.85±0.07), (0.54±0.04)) in SD group were all higher (all P<0.05). Compared with SD group, the protein levels of P2X7 (0.74±0.05), NLRP3 (0.78±0.02), caspase-1 (0.74±0.04), ASC (0.67±0.02), IL-1β (0.53±0.07) in SD+ BBG group were all lower (all P<0.05). (4)There were statistically significant differences in the mRNA levels of IL-18, IL-1β, TNF-α, CD86 and CD206 in hippocampus among the three groups ( F=12.80, 12.28, 105.80, 7.06, 30.19, all P<0.05). The mRNA levels of IL-18, IL-1β, TNF-α, CD86 in SD group were all higher than those in CC group(all P<0.05), while the mRNA level of CD206 in SD group was lower than that in CC group( P<0.05). Compared with SD group, the mRNA levels of IL-18, IL-1β, TNF-α, CD86 were lower in SD+ BBG group (all P<0.05), while the CD206 mRNA level of SD+ BBG group was higher than that in SD group( P<0.05). Conclusion:SD intervention can lead to cognitive impairment and increased expression of P2X7 in hippocampus of mice, which may be related to the activation of P2X7/ NLRP3 inflammasome signaling pathway, promoting the polarization of microglia into pro-inflammatory type and up-regulating the expression of pro-inflammatory cytokines.Inhibition of P2X7 can improve the cognitive function of mice.

Background: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is increasingly recognized as a manifestation preceding the α-synucleinopathies like Parkinson’s disease (PD). Neurofilament light chain (NfL) have been reported to be higher in synucleinopathies as a sign of neurodegeneration. Objective: To evaluate whether plasma NfL is valuable in reflecting cognitive and motor status in iRBD and PD with a premorbid history of RBD (PDRBD), and predicting disease progression in iRBD. Methods: Thirty-one patients with iRBD, 30 with PDRBD, and 18 healthy controls were included in the cross-sectional and prospective study. Another cohort from the Parkinson’s Progression Markers Initiative (PPMI) dataset was enrolled for verification analysis. All patients received evaluations of cognitive, motor, and autonomic function by a battery of clinical tests at baseline and follow-up. Blood NfL was measured by the Quanterix Simoa HD-1. Results: In our cohort, 26 patients with iRBD completed the follow-up evaluations, among whom eight (30.8%) patients displayed phenoconversion. Baseline plasma NfL cutoff value of 22.93 pg/mL performed best in distinguishing the iRBD converters from non-converters (sensitivity: 75.0%, specificity: 83.3%, area under the curve: 0.84). Cognitive and motor function were significantly correlated with NfL levels in PDRBD (correlation coefficients: –0.379, 0.399; respectively). Higher baseline NfL levels in iRBD were significantly associated with higher risks for cognitive, motor, autonomic function progression, and phenoconversion at follow-up (hazard ratios: 1.069, 1.065, 1.170, 1.065; respectively). The findings were supported by the PPMI dataset. Conclusion: Plasma NfL is valuable in reflecting disease severity of PDRBD and predicting disease progression and phenoconversion in iRBD.

Objective:To investigate the characteristics of transcranial sonography (TCS) in patients with restless legs syndrome (RLS), and analyze the correlations of scores of RLS Self-rating Severity Scale by International Restless Leg Syndrome Study Group (IRLS) and TCS parameters with clinical data of these patients.Methods:Twenty-one patients with RLS admitted to the Sleep Disorder Clinic of our hospital from September 2020 to January 2021 were selected as RLS group, and 23 healthy controls at the same time period were recruited as control group. IRLS was used to evaluate the severity of patients in the RLS group, and the 14-item Hamilton anxiety rating scale (HAMA-14) and 24-item Hamilton depression rating scale (HAMD-24) were used to evaluate the anxiety and depression of subjects from the 2 groups. Pittsburgh Sleep Quality Scale (PSQI), Insomnia Severity Index (ISI) and Epworth Sleepiness Scale (ESS) were used to evaluate the sleep quality of subjects from the 2 groups. TCS was used to examine the occurrence of hypoechoic substantia nigra and raphe nucleus rupture and the width of the third ventricle in the two groups. The clinical data and TCS parameters of patients in the 2 groups were compared, and the correlations of IRLS scores and TCS parameters with clinical features of patients in the RLS group were analyzed.Results:As compared with those in the control group, the HAMA-14, HAMD-24, ISI and PSQI scores in the RLS group were statistically higher ( P<0.05). As compared with the control group, RLS group had significantly higher proportion of patients with hypoechoic substantia nigra or raphe nucleus rupture ( P<0.05). In RLS patients, the IRLS scores were positively correlated with HAMA-14, HAMD-24, and ISI scores ( P<0.05); ESS scores were negatively correlated with hypoechoic substantia nigra and width of the third ventricle ( rs=-2.005, P=0.045; r=-0.477, P=0.029); width of the third ventricle was negatively correlated with gender (male) and years of education ( rs=-0.592, P=0.005; r=-0.627, P=0.002), and positively correlated with age and course of the disease ( r=0.756, P<0.001; r=0.167, P=0.047). Conclusions:Patients with RLS are prone to anxiety, depression and sleep disorders; their TCS shows hypoechoic substantia nigra and raphe nucleus rupture. RLS severity may affect HAMA-14, HAMD-24, and ISI scores. Gender, age, years of education, course of disease, and ESS scores of RLS patients may affect TCS related parameters.

Purpose Studies have shown that individuals with insomnia experience more frequent and longer episodes of mind wandering (MW) while driving. However, the effect of the interaction between insomnia and MW on driving behavior is not fully understood. This study aimed to gain deeper insights into the relationships among insomnia, MW, and driving behavior. Patients and methods Forty-two participants (21 diagnosed with insomnia and 21 controls) were recruited, and subjective sleep quality and cognitive function were assessed. A driving simulator experiment with a within-subject design was performed, involving two distraction tasks (no-distraction task versus MW task) and two driving scenarios (lane-keeping versus lane-changing). Results In the lane-keeping scenario, there was no significant between-group difference (people with insomnia and controls) in longitudinal driving performance for the no-distraction task, although the interaction between MW and insomnia significantly increased drivers’ longitudinal control variation. Correlation analysis confirmed that longitudinal driving performance was positively correlated with sleep quality and the cognitive level. Unlike longitudinal driving performance, lateral driving performance was significantly weaker in people with insomnia than in controls under both distraction tasks. In the lane-changing scenario, although there was no between-group difference in driving performance, the MW task led to significant changes in driving performance within each group compared with the no-distraction task, and these findings were associated with cognitive function, but not with sleep quality. Conclusion These findings show that insomnia and MW combined can lead to reduced driving performance. Further research is needed to elucidate the factors that influence this phenomenon.

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.

Insomnia is associated with fatigue and poor driving performance, thus increasing the risk of traffic accidents. This study aimed to evaluate the effect of fatigue on driving in patients with chronic insomnia in a free-flow traffic scenario and car-following scenario, and to investigate the relationships between driving performance, cognitive function, and insomnia. The Trail Making Test (TMT), Stroop Color and Word Test (SCWT), Symbol Digit Modalities Test (SDMT), and Digit Span Test (DST) of 15 participants with mild-to-moderate chronic insomnia and 16 healthy participants were assessed. During the fatigue driving task, drivers completed simulated driving tasks under free-flow traffic and car-following scenarios. The mean speed (MS), mean acceleration (MA), mean lateral position (MLP), and standard deviation of lateral position (SDLP) were measured to assess driving performance. During fatigued tasks, the MA and MLP in the free-driving scenario were higher than those in the car-following scenario (P < 0.01), the SDLP was higher in the insomnia group than in the healthy group (P = 0.02), and the interaction effect was significantly different for MLP between the groups (P = 0.03). MS was negatively correlated with TMT score, SDMT score, and DST score, and positively correlated with time to complete TMT, errors in SCWT, and time to complete SCWT. SDLP was negatively correlated with DST score and positively correlated with time to complete SCWT. Furthermore, the insomnia group had poorer lateral vehicle control ability than the healthy group. The insomnia group had a more impaired driving performance in the free-driving scenario than in the car-following scenario. Drivers with impaired cognitive function exhibited impaired driving performance.

Objective:To investigate the correlation between single nucleic acid polymorphisms (SNPs) of MEIS1, BTBD9, MAP2K5, PTPRD and restless leg syndrome (RLS).Methods:By searching the literatures published before March 1, 2021 at home and abroad, case-control studies on risk genes associated with RLS were collected, and the Review Manager 5.3 and Stata 15.1 softwares were used for statistical analysis.Results:A total of 8 studies were included, with a total of 7 824 cases and 14 645 controls.Meta analysis results showed that the SNPs locus of the risk gene associated with RLS was MEIS1 rs2300478( OR=1.68, 95% CI: 1.59-1.78), BTBD9 rs9296249( OR=1.62, 95% CI: 1.47-1.77), BTBD9 rs9357271( OR=1.49, 95% CI: 1.44-1.55), MAP2K5 rs12593813( OR=1.44, 95% CI: 1.36-1.53), MAP2K5 rs11635424( OR=1.47, 95% CI: 1.34-1.60)and PTPRD rs1975197( OR=1.34, 95% CI: 1.21-1.49). Conclusion:MEIS1 rs2300478, BTBD9 rs9296249, BTBD9 rs9357271, MAP2K5 rs12593813, MAP2K5 rs11635424 and PTPRD rs1975197 are the risk loci of RLS.

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.

脑血管病高发病率和高致残率给患者本人、家庭和社会造成巨大的负担.急性脑血管病中睡眠障碍的发生率较高,对脑血管病患者的预后产生重要影响.本文就急性脑血管患者睡眠障碍的处理作一综述.

失眠是成人癌症患者的常见症状之一,在癌症病程的各个阶段都很常见,不仅影响患者的生活质量,甚至会影响到抗癌治疗和疾病结局.为进一步规范成人癌症患者失眠的诊治,中国癌症基金会肿瘤心理学协作组组织肿瘤科、精神科和以科室名称"肿瘤心理科"等开展精神卫生临床工作的多学科专家,结合国内外相关诊疗指南、循证医学证据和专家临床经验撰写本专家建议,内容包括流行病学、病因、失眠对癌症及其治疗的影响、评估及治疗过程,以及诊疗要点和注意事项,旨在引发肿瘤临床医护人员对成人癌症患者失眠问题的关注,并为成人癌症患者失眠的诊治提供指导.

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.

睡眠是生命所必需的生理条件,存在于所有具有神经和胶质网络的生物体中.它的功能包括维持能量代谢,调节免疫系统和大脑功能,调节突触可塑性和消除代谢产物.睡眠不足及睡眠质量下降与机体多种功能障碍相关,包括心血管事件、心功能不全、消化系统障碍、炎症与免疫、代谢障碍、神经系统障碍等多个方面,本文就睡眠障碍对机体功能的影响做一综述.

STUDY OBJECTIVES:The relationship of iron with cognitive and motor impairment in idiopathic rapid eye movement sleep behavior disorder (iRBD) remains unknown. METHODS:Twenty-nine (29) patients and 28 healthy controls (HCs) underwent susceptibility weighted imaging and susceptibility mapping. These images were used to evaluate the nigrosome-1 (N1) sign in the substantia nigra (SN), global and regional high-iron (RII) content, and volume of subcortical nuclei. RESULTS:The number of iRBD patients with N1 loss (12) was significantly higher than HCs (2) (p = 0.005). Compared with HCs, the iRBD patients had reduced volume of the right caudate nucleus (RCN) (p < 0.05, false discovery rate [FDR] correction) but no significant changes in global and RII iron of the subcortical nuclei (all p > 0.05, FDR correction). Multiple regression analysis revealed that: for cognitive function, the RII iron of the RCN was significantly correlated with visuospatial function and the global iron of the right dentate nucleus (RDN) was correlated with memory function; for motor function, the RII iron of the left DN (LDN) and global iron of the left CN correlated with the Alternate-Tap test (left, average), the global iron of the LDN correlated with the Alternate-Tap test (right), and the global iron of the left GP correlated with the 3-m Timed Up and Go test (all p < 0.05, FDR correction). CONCLUSIONS:Our exploratory analysis found that iRBD patients had a higher incidence of N1 loss and reduced RCN volume after FDR correction. Cognitive and motor impairment were associated with iron deposition in several cerebral nuclei after FDR correction.

猝倒型发作性睡病是一种睡眠-觉醒障碍疾病,发病可能与免疫、遗传、环境、感染、中枢神经系统退行性病变等因素有关,近年来神经影像学技术的发展促进了我们对猝倒型发作性睡病生物学机制的理解.该文汇总了猝倒型发作性睡病患者最新的神经影像学进展,以期阐明该病可能的神经影像学特征.