Objective: To explore the effects of ApoE epsilon4 (ApoE-ε4) alleles on cognitive function and resting-state functional MRI (rs-fMRI) in patients with amnestic mild cognitive impairment(aMCI) based on a prospective cohort study. Methods: An average of 20 months of prospective observations were conducted on 16 ApoE-ε4-carriers and 24 non-carriers of aMCI. Neuropsychological assessments and rs-fMRI data were collected at both baseline and follow-up. All participants were assessed by a battery of neuropsychological tests and underwent rs-fMRI. Two core regions of the default mode network (DMN), the left posterior cingulate cortex (PCC) and the medial prefrontal cortex (mPFC), were selected as seeds to calculate the functional connectivity. Two-way repeated measures analysis of variance was used to assess the effects of ApoE genotype(ε4-carriers, nonε4-carriers), interval and the interaction between these two factors for functional connectivity extracted from changed region found by t-test.Conversion rates of dementia were compared between ApoE-ε4-carriers and nonε4-carriers at follow-up using Chi-square test. For the comparison of functional connectivity and clinical data between ApoE-ε4-carriers and nonsε4-carriers in baseline and follow-up, the normal distribution test was carried out first. If the normal distribution was fitted, the two-sample t test was used, otherwise, the Mann-Whitney rank sum test was used. Finally, the general linear model was used to assess the relationships between alterations in functional connectivity and in neuropsychological assessments as well as the interaction effect. Results: (1)Significant decline in memory domains were found in ApoE-ε4-carriers as compared to non-carriers at both baseline and follow-up. The ApoE-ε4-carriers (14/16) presented a higher conversation rate than non-carriers(13/24, χ²=4.862, P=0.027) at follow-up. (2)Functional imaging analysis revealed that ApoE-ε4-carriers exhibited significantly higher functional connectivity between the left PCC and the left angular (ApoE-ε4-carriers: 0.23±0.11, non-carriers: -0.03±0.13, t=4.800, cluster size: 1 944 mm³, P=0.004), and between the left mPFC and the left angular (ApoE-ε4-carriers: 0.33±0.21, non-carriers: 0.08±0.18, t=5.040, cluster size:1 836 mm³, P=0.006) as compared to non-carriers at follow-up. We detected significant effect for the interaction interval by ApoE-ε4 on functional connectivity between the left angular and the left PCC (F=10.833, P=0.002)as well as the left mPFC (F=7.280, P=0.010). (3)The alteration of functional connectivity value between the left mPFC and the left angular in ApoE-ε4-carriers was positively correlated with the changes ofimmediate memory (r=0.692, P=0.018). The correlation was not statistically significant in ApoE-ε4-noncarriers (r=-0.198, P=0.417) and the integration effect was significant (F=8.632, P=0.006). Conclusions The ApoE-ε4 actually accelerates the deterioration of cognitive function in aMCI patients and carriers presented relatively reserved functional connectivity between the left angular and other core regions within DMN, which indicated the disruption of functional connectivity may be one of the underline mechanisms of ApoE-ε4 during AD process.

Objective To investigate the regulatory effect of cognitive behavioral therapy (CBT) on the functional connectivity of cognitive control network in untreated obsessive-compulsive disorder (OCD) patients,so as to provide evidence for understanding the neurobiological mechanism of CBT.Methods A total of 45 OCD patients and 45 matched normal controls were recruited at the outpatient clinic in Beijing Anding Hospital.Four therapists provided 14 times of CBT treatment for OCD patients.All subjects underwent clinical symptom assessment and magnetic resonance imaging at baseline and at the end of 12 weeks.The clinical symptoms were assessed by the psychiatrists using Y-BOCS,HAMD17 and HAMA.The clinical symptoms of OCD patients before and after CBT treatment were compared.The GRETNA software package was used to preprocess the resting-state fMRI data.The whole brain function network was constructed with the template of Power 264 functional brain area as the network node.The function connection intensity outside the cognitive control network was calculated,and the function connection of 2 groups of brain networks at two timepoints were compared by repeated measurement of variance analysis.Results A total of 41 patients completed CBT.The scores of obsessive-compulsive symptoms,anxiety symptoms and depressive symptoms decreased at the end of 12th week,of which 32 patients were improved (Y-BOCS reduction ≥35％).Single factor repeated analysis of variance and post hoc tests were performed between patients with improvement and normal controls.At baseline,the functional connection between the cingulo-opercular network and the salience network of OCD patients was lower than that of the normal control (0.172±0.060 vs.0.215±0.076,t=1.731,P=0.040),it increased after treatment (0.186±0.171 vs.0.172±0.060,t=2.480,P=0.010).At baseline,the functional connection of cingulo-opercular network and subcortical network in OCD patients was lower than that of normal control (0.119±0.081 vs.0.129±0.070,t=1.640,P=0.040),and it increased after treatment (0.130±0.161 vs.0.119±0.081,t=2.421,P=0.020).At baseline,the functional connection between the frontal-parietal network and subcortical network was lower than that of normal controls (-0.004 ± 0.039 vs.0.021 ± 0.054,t=2.280,P=0.020),and it increased after treatment (0.020±0.042 vs.-0.004±0.039,t=-2.300 P=0.020).Conclusions CBT could effectively improve obsessive-compulsive symptoms accompanying with improvement of the external functional connectivity of cognitive control network in OCD patients.

Objective To investigate the regulatory effect of cognitive behavioral therapy (CBT) on the functional connectivity of cognitive control network in untreated obsessive-compulsive disorder (OCD) patients,so as to provide evidence for understanding the neurobiological mechanism of CBT.Methods A total of 45 OCD patients and 45 matched normal controls were recruited at the outpatient clinic in Beijing Anding Hospital.Four therapists provided 14 times of CBT treatment for OCD patients.All subjects underwent clinical symptom assessment and magnetic resonance imaging at baseline and at the end of 12 weeks.The clinical symptoms were assessed by the psychiatrists using Y-BOCS,HAMD17 and HAMA.The clinical symptoms of OCD patients before and after CBT treatment were compared.The GRETNA software package was used to preprocess the resting-state fMRI data.The whole brain function network was constructed with the template of Power 264 functional brain area as the network node.The function connection intensity outside the cognitive control network was calculated,and the function connection of 2 groups of brain networks at two timepoints were compared by repeated measurement of variance analysis.Results A total of 41 patients completed CBT.The scores of obsessive-compulsive symptoms,anxiety symptoms and depressive symptoms decreased at the end of 12th week,of which 32 patients were improved (Y-BOCS reduction ≥35％).Single factor repeated analysis of variance and post hoc tests were performed between patients with improvement and normal controls.At baseline,the functional connection between the cingulo-opercular network and the salience network of OCD patients was lower than that of the normal control (0.172±0.060 vs.0.215±0.076,t=1.731,P=0.040),it increased after treatment (0.186±0.171 vs.0.172±0.060,t=2.480,P=0.010).At baseline,the functional connection of cingulo-opercular network and subcortical network in OCD patients was lower than that of normal control (0.119±0.081 vs.0.129±0.070,t=1.640,P=0.040),and it increased after treatment (0.130±0.161 vs.0.119±0.081,t=2.421,P=0.020).At baseline,the functional connection between the frontal-parietal network and subcortical network was lower than that of normal controls (-0.004 ± 0.039 vs.0.021 ± 0.054,t=2.280,P=0.020),and it increased after treatment (0.020±0.042 vs.-0.004±0.039,t=-2.300 P=0.020).Conclusions CBT could effectively improve obsessive-compulsive symptoms accompanying with improvement of the external functional connectivity of cognitive control network in OCD patients.

Objective To explore a new index for reflecting the topological information of brain functional networks in patients at high risk of Alzheimer disease using characteristics of resting-state functional connectivity strengths(FCS) in patients with amnestic mild cognitive impairment(aMCI). Methods Thirty-one aMCI patients and 42 age, gender and years of education matched normal controls were enrolled between September 2009 and April 2011 in this study. The resting-state functional MRI (rs-fMRI) data of all participants were acquired and preprocessed. Then the whole-brain functional connectivities were constructed for exploring the distribution characteristics of hub regions which had higher FCS values. Using two-sample t test to compare group differences in age, years of education and each neuropsychological assessment. In addition, using Chi-squared test to compare group differences in gender. Group differences in FCS values were analyzed by general linear model. Finally, correlation analyses were used to evaluate the relationships between the FCS values of the brain regions with group differences and behavioral scores in aMCI patients. Results The hub regions of the functional networks in the aMCI patients were mainly located in the association cortices such as the precuneuses, posterior cingulate cortices, medial prefrontal cortices, angular gyri, superior occipital gyri, fusiform gyri and lingual gyri. The distribution models in the aMCI patients were consistent with those in the normal controls. However, the FCS values of these brain regions were significantly lower in the aMCI patients than those in the normal controls. In comparison to the normal controls, the aMCI patients had significantly decreased FCS values in the bilateral fusiform gyri, lingual gyri, superior occipital gyri, left middle occipital gyrus and postcentral gyrus (the cluster was 389, 230, 187 and 107 voxels, respectively;P<0.05, respectively), and they had decreased trends of FCS values in the bilateral posterior cingulate cortices and right insulas. The correlation analysis with uncorrected conditions showed that the FCS values of the left postcentral gyri were correlatid with the clock drawing test (CDT) scores (r=0.436, P=0.026). Conclusions aMCI mainly attacks the hub regions of brain functional networks. The changes of functional connectivities in aMCI may reflect the early pathophysiologic alterations of AD.

Objective To investigate the protective effects of isopimaric acid ( ISO), the BKCa channel activator, on cognitive function and synaptic plasticity in APP/PS1 mice. Methods Alzet osmotic pump was loaded with ISO or DMSO only and assembled with ALZET Brain Infusion Kit III. The cannula was implanted into the lateral ventricle of 4-month-old male APP/PS1 mice or matched wild type ( WT) mice. Two weeks later, open field test and Morris water maze were conducted. Paired-pulse facilitation ( PPF) and TBS-induced long-term potentiation ( LTP ) were recorded in CA1 region of hippocampus. Results The open field test showed that there was no significant difference among the four groups in spontaneous activities and vertical plane movement distance within 30 minutes. Floor plane movement distance was significantly greater in APP/PS1+DMSO group than that in WT+DMSO group(P<0.05) . Compared with the WT+DMSO group, APP/PS1+DMSO group had significantly longer escape latency from the third to fifth day and lower percentage of time spent in the target quadrant ((43.27±3.24)% vs (34.19±2.56)%) and the number of crossing through the platform ((4.25±0.66)times vs (1.93±0.33)times)(P<0.05). Compared with the APP/PS1+DMSO group, the APP/PS1+ISO group had significantly shorter escape latency from the fourth to fifth day and higher percentage of time spent in the target quadrant ((46.16±3.51)%) and the number of crossing through the platform ((3.41±0.34) times) (P<0.05). PPF in APP/PS1+DMSO group significantly reduced compared with that in WT+DMSO group at 30-50ms interstimulus interval(P<0.05). PPF in APP/PS1+ISO group((224.50±13.79)%) was significantly augment compared with APP/PS1+DMSO ((174.99 ±6.68)%) group at 40 ms interstimulus interval (P<0.05). The LTP at 60 min post-TBS was significantly smaller in the APP/PS1+DMSO group ((135.19±1.32)%) than that in the WT+DMSO group ((172.17± 4.15)%)(P<0.001). The LTP of the APP/PS1+ISO group((160.48±1.19)%) became significantly in-creased compared with that in the APP/PS1+DMSO group(P<0.001).Conclusion BKCa channel activator ISO improve the learning and memory function of APP/PS1 mice by promoting PPF and increasing LTP to recover synaptic plasticity in the hippocampus.

OBJECTIVE To understand the disinfection,use and management of ventilator for the sake of regulation.METHODS By interviewing and on-site survey,we understanded the method and the process of disinfection and found out the using cycle of the ventilator system and the conditions of its management.RESULTS Among 44 ventilators 7 models were found:the management of 18 ventilators was irregular;the other 26 ventilators were disinfected by 2 kind and 4 types disinfect methods.their using cycles were unsure,their processes of disinfection were irregular.The responsibilities for the disinfection were unclear,lacking of monitoring the effect of disinfection and their management was irregular.CONCLUSIONS The disinfection of ventilator using and management must be regulated.