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Objective:To explore the correlation and mechanism between thalamic network abnormality and cognitive decline in patients with temporal lobe epilepsy (TLE).Methods:A total of 53 patients with unilateral TLE were consecutively enrolled through the epilepsy clinic of the First Affiliated Hospital of Guangxi Medical University from December 2018 to February 2020. During the same recruitment interval, 37 health controls(HC) with matching demographic characteristic were recruited. All subjects were received the Montreal cognitive assessment(MoCA) test and multimodal MRI scanning. Voxel-based morphometry method was used to study the changes of thalamic gray matter volume in patients with unilateral TLE. The structural covariance network and functional connectivity network based on seed points were used to analyze the changes of thalamic network in TLE patients. In addition, the correlations among abnormal thalamic structure, thalamic network and cognitive function score were analyzed. SPSS 22.0 software was used for statistical analysis. Independent sample t-test and Mann Whitney U test were used for inter group comparison. In order to explore the relationship between thalamus and thalamic network and cognitive performance in TLE patients, thalamic volume and gray matter volume and functional connection value of brain areas with abnormal synergistic changes were extracted and correlated with MoCA score. Results:The total score of MoCA in TLE patients (27.0(25.0, 29.0)) was significantly decreased compared with HC (29.0(28.0, 30.0))( Z=-4.601, P<0.001). Whole brain gray matter volume analysis showed that compared with HCTLE patients showed significant volume reduction in left cerebellum, right temporal pole, right fusiform gyrus, straight gyrus, bilateral middle temporal gyrus, thalamus, medial and paracingulate gyrus (GRF adjusted, voxel-level P<0.001 and cluster-level P<0.05). The thalamus-associated structural covariance network analysis revealed that compared with healthy controls, TLE patients exhibited decreased connectivity in right fusiform gyrus (MNI: x=28.5, y=-15.0, z=-34.5), left insula (MNI: x=-33.0, y=-18.0, z=-1.5), right middle temporal gyrus (MNI: x=55.5, y=-51.0, z=9.0), left complementary motor area (MNI: x=-10.5, y=1.5, z=57.0) and right posterior central gyrus (MNI: x=31.5, y=-33.0, z=51.0) ( P<0.001, cluster > 100). The thalamus-associated functional connectivity network analysis revealed that TLE patients exhibited decreased connectivity in left insula (MNI: x=-38, y=-7, z=-7), left lingual gyrus (MNI: x=-6, y=-81, z=-12), right lingual gyrus (MNI: x=15, y=-105, z=0) and left triangular inferior frontal gyrus (MNI: x=-39, y=36, z=-6) (GRF correction, voxel-level P<0.001 and cluster-level P<0.05). Volume of left insula which had decreased structural connectivity with thalamus were positively correlated with the MoCA score in TLE patients( r=0.279, P=0.043). Volume of left complementary motor area which had decreased structural connectivity with thalamus was positively correalated with the MoCA score and language score in TLE patients( r=0.323, P=0.018; r=0.334, P=0.015). Volume of left lingual gyrus which had decreased functional connectivity with thalamus was negatively correalated with the memory score in TLE patients ( r=-0.331, P=0.016). Conclusion:Thalamic volume, thalamic structural covariant network and functional connection network are changed in TLE patients. The abnormality of thalamic network is associated with cognitive performance in TLE patients, which may be the neural mechanism of thalamus participating in the cognitive impairment of TLE patients.
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Objective:To investigate longitudinal alterations of brain functional complex network by rest-stage functional magnetic resonance imaging (rs-fMRI) and graph theory in patients with temporal lobe epilepsy (TLE).Methods:A total of 13 TLE patients (TLE baseline group) and 13 healthy controls (healthy control group) were enrolled to observe alterations in complex functional network. The subjects were recruited in the Epilepsy Clinic of the First Affiliated Hospital of Guangxi Medical University from January 2015 to April 2018. For longitudinal analysis, TLE patients were followed-up for three years (TLE follow-up group). All participants underwent rs-fMRI and attention network test (ANT). Finally, a cross-sectional study was conducted by comparing the area under the curve (AUC) between the TLE baseline group and the healthy control group, and a longitudinal analysis was conducted by comparing the AUC between the TLE baseline group and the TLE follow-up group.Results:Cross-sectional analysis showed that the alerting function of the TLE baseline group was declined [The tonic alertness reaction time, phasic alertness reaction time and alertness were (727.00±126.07) ms, (692.85±132.37) ms, and (34.15±23.50) ms, respectively in the TLE baseline group, which were (639.87±81.41) ms, (589.50±80.59) ms, and (50.37±14.71) ms, respectively in the healthy control group, with statistically significant differences between the two groups ( t=-2.09, P=0.047; t=-2.41, P=0.024; t=2.11, P=0.045)]; the TLE baseline group demonstrated decreased clustering coefficient in left supplementary motor area (SMA.L)(AUC was 0.162±0.044, 0.189±0.021, respectively; t=-4.14, P=4.67E-04) and left inferior parietal supramarginal angular gyri (AUC was 0.178±0.021, 0.202±0.026, respectively; t=-2.42, P=0.024), and decreased nodal local efficiency in SMA.L (AUC was 0.239±0.045, 0.260±0.022, respectively; t=-4.13, P=4.77E-04) and left inferior temporal gyrus (AUC was 0.233±0.036, 0.253±0.027, respectively; t=-3.03, P=0.006) compared with the healthy control group, and both SMA.L clustering coefficient and nodal local efficiency were positively correlated with TLE patients′ duration ( r=0.652, P<0.05; r=0.611, P<0.05). Longitudinal analysis showed that the global network efficiency of the TLE follow-up group decreased (The AUC of the TLE baseline group was 0.182±0.008, and the AUC of the TLE follow-up group was 0.169±0.015, t=2.73, P=0.017), which was negatively correlated with alertness ( r=-0.617, P<0.05). Conclusions:TLE patients show impairment of topological properties of brain functional network. SMA.L is a significant node in network. Alterations of brain functional network associate with duration. The decline in global network efficiency may be a characteristic of progressive deficit to TLE.
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Objective@#To examine the prospective association between peripubertal diet quality and pubertal timing.@*Methods@#Multivariate regression analyses were performed using data obtained from 1 588 SCCNG (Southwest China Childhood Nutrition and Growth) study participants, which included dietary data, anthropometric parameters, and information about potential confounders during peri puberty, two and four years before the onset of menarche or voice break. Dietary intake in peri puberty was assessed using a validated food frequency questionnaire. Diet quality was determined using the Chinese Children Dietary Index (CCDI), which measures adherence to current dietary recommendations. Age at menarche or voice break (M/VB) were used as pubertal markers.@*Results@#The CCDI score ranged from 58.0 to 132.5 for girls and from 48.3 to 129.9 for boys. The pubertal markers consistently indicated that girls and boys with a higher peripubertal diet quality entered puberty later than their counterparts with lower CCDI scores (higher vs. lower CCDI tertiles: age at M was 13.1 years (11.2-13.3) and 12.5 years (12.0-13.9)(P<0.01); VB was 13.8 years (12.1-14.8) and 13.4 years (12.5-15.1)（P=0.03), after adjusting for paternal education level, energy intake, and pre pubertal body fat.@*Conclusion@#Children with a higher diet quality during peri puberty entered puberty at a later age. Dietary guidance and intervention are needed for better dietary quality among children during pubertal transition.
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Objective@#To explore the prospective effect of dietary intake of total fat and fatty acids on menarcheal timing among girls,and to provide a theoretical basis for preventing the early puberty development of Chinese children.@*Methods@#Using the data from 1997-2015 China Health and Nutrition Survey (CHNS), 1 240 girls aged 6-13 with menarche information, baseline dietary survey data and at least one follow up assessment were selected. Cox regression analysis was performed to examine the prospective effect of dietary intake of total fat and fatty acids before menarche on age at menarche.@*Results@#The mean baseline age of the participants was (8.3±1.8). After adjustment for year of birth, residence, household income, dietary energy intake and body mass index Z score at baseline, girls in the highest quartile of intake of total fat and polyunsaturated fatty acid (PUFA) had a 30% and 34% higher probability of experiencing menarche at an earlier age than those in the lowest quartile [ HR(HR 95%CI )=1.30 (1.01~1.68)，1.34(1.05~1.70)]. After adjusting for the confounders, there were no correlations between the intake of saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) and the onset of menarche [ HR(HR 95%CI )=1.24(0.98~1.58),1.25(0.97~ 1.62 )]( P >0.05).@*Conclusion@#Higher dietary intake of total fat and PUFA before menarche may lead to earlier age at menarche and no correlation between intake of SFA and MUFA before menarche with age at menarche is found among Chinese girls.
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OBJECTIVE:To study the effects of aripiprazole on PC12 cell injury induced by amyloid β-protein(Aβ25-35)and its mechanism. METHODS:PC12 cells were randomized into normal control group,model group (20 μmol/L Aβ25-35),aripiprazole low-concentration,medium-concentration and high-concentration groups(5,10,20 μmol/L aripiprazole+20 μmol/L Aβ25-35). These groups were cultured with culture medium containing relevant medicine for 48 h,with 6 wells in each group. The viability(optical density value)of PC12 cell was measured by MTT assay,and PC12 cell apoptosis was measured by Hoechst staining. The activi-ties of Caspase-3 and Caspase-9 were determined by spectrophotometry. The protein expression of Bcl-2,Bax and PI3K and the phosphorylation of Akt were assayed by Western blot assay. RESULTS:Compared with normal control group,optical density value of model group was decreased while apoptotic rate was increased;the activities of Caspase-3 and Caspase-9,and the protein expres-sion of Bax were increased;the protein expression of Bcl-2 and PI3K,the phosphorylation of Akt were decreased(P<0.01). Com-pared with model group,optical density value of aripiprazole low-concentration,medium-concentration and high-concentration groups were increased,while apoptotic rate and the activities of Caspase-3 and Caspase-9 were decreased;the protein expression of Bcl-2 and PI3K and the phosphorylation of Akt were enhanced;while the protein expression of Bax were decreased in aripiprazole medium-concentration and high-concentration groups(P<0.05 or P<0.01). CONCLUSIONS:Aripiprazole can suppress cell apop-tosis of PC12 cell induced by Aβ25-35,which is related to activating PI3K/Akt signal pathway.
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OBJECTIVE:To investigate clinical efficacy and adverse reactions(ADRs)of 4 kinds of the second-generation anti-psychotic drugs in the treatment of acute phase of schizophrenia. METHODS:159 patients with schizophrenia were randomly divid-ed into risperidone group(40 cases),olanzapine group(40 cases),aripiprazole group(39 cases)and ziprasidone group(40 cas-es). All groups were given routine dosage of relevant medicine by routine usage for 6 weeks. Mental status of patients were mea-sured by PANSS before treatment and after 2,4 and 6 weeks of treatment. At the same time,blood glucose,blood lipid,prolac-tion and other metabolic and biological indicators were all detected. RSESE,BARS and UKU were adopted to evaluate ADR. RE-SULTS:A total of 100 patients completed the study. Compared with aripiprazole group and ziprasidone group,risperidone and olan-zapine inhibited symptom more rapidly,with statistical significance (P<0.05). After treatment,body mass index and abdominal circumference of olanzapine group were significantly higher than those of other 3 groups,with statistical significance (P<0.05). Low density lipoprotein of olanzapine group was increased significantly,there was statistical significance compared to ziprasidone group and aripiprazole group(P<0.05). Prolactin level of risperidone group was significantly higher than those of other 3 groups, while that of aripiprazole group was significantly lower than those of other 3 groups,with statistical significance(P<0.05). ADRs of 4 drugs were mild or moderate,most of whom could be alleviated by symptomatic treatment. CONCLUSIONS:In the treatment of acute phase schizophrenia,4 drugs of the second-generation have similar curative effect in symptoms control,among which ris-peridone and olanzapine inhibit positive symptom more rapidly while more ADRs that related to lipid and glucose metabolism and prolactin also show. Aripiprazole and ziprasidone induce less ADRs relatively,and patients show better tolerability. Physicians should consider all kinds of factors in drugs selection,and make individualized treatment plan.
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Objective To explore the localization diagnosis method of lumbar intervertebral foramen stenosis by multi-di-mensional MRI scans of lumbar nerve roots. Methods Twenty-one patients with lumbar intervertebral foramen stenosis were fol-lowed up from June 2006 to June 2011 postoperatively, 10 cases of male, 11 cases of female;36 to 65 years old, average 45.6 years. The medical history is six to thirty six months, an average of 9.4 years;5 cases have low back pain with unilateral leg pain and 16 cases showed unilateral leg pain only. The height of intervertebral space and foramen intervertebrale were measured on the X-rays of lumbar lateral position. Lumbar nerve roots MR imaging at the position of axial, coronal and sagittal scan were performed separately to the patients who were clinically suspected to suffer from lumbar intervertebral foramen stenosis. A definitive diagno-sis of the location of nerve root compression and structural changes surrounding the nerve root can be obtained. Surgical operation was performed to confirm the accuracy of the MRI imaging diagnosis. Results There were 9 cases of lumbar intervertebral fora-men stenosis caused by lumbar disc herniation. The other 12 cases are caused by zygapophyseal joint hyperplasia. All cases of lumbar intervertebral foramen stenosis located at the low back. By comparing MR images of lumbar intervertebral foramen stenosis with surgical procedure,the surgical observation of 21 patients completely coincided with the preoperative localization diagnosis, coincidence rate was 100%(21/21). After surgical treatment, 20 cases achieved a complete remission of leg pain and 1 case was not satisfactory. Conclusion MRI imaging at the position of axial, coronal and sagittal scan for lumbar nerve roots were useful to rigorous localization diagnosis of lumbar intervertebral foramen stenosis, and can provide accurate radiological evidence for sur-gery program.
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ObjectiveTo assess the association of rs1344706 and rs4667001 polymorphism of ZNF804A gene with schizophrenia,and the relationship between rs1344706 polymorphism and antipsychotic drug efficacy.MethodsThe studies concerning association of ZNF804A gene polymorphism with schizophrenia and its drug efficacy were retrieved in databases such as Medline and CNKI,and then screened according to the inclusion and exclusion criteria.Meta-analysis was performed by RevMan 5.1 following quality assessment and data extraction.ResultsEleven high-quality studies under the criteria were included.For rs1344706,T allele frequency was significant higher in the schizophrenia group than control group ( OR=1.13,95％ CI (1.06-1.21 ),P=0.0003).Moreover,for rs4667001,G allele frequency was significant higher in the schizophrenia group ( OR =1.14,95％ CI( 1.04-1.26),P =0.005 ).In addition,the difference of PANSS scores reduction between T allele and GG genotype carriers was not significant in both positive and negative symptoms after four-week treatment,and the same trend of difference was in the comparison between TT genotype and G allele carriers.ConclusionThe data supports that T allele of rs1344706 and G allele of rs4667001 in ZNF804A gene are associated with the susceptibility of schizophrenia,but rs1344706 polymorphism is not related to antipsychotic drug efficacy.
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Objective To investigate the potential association of Ghrelin(GHRL)gene polymorphisms susceptible to schizophrenia by case-control study.Methods Six hundred and thirty-four patients,six hundred and six healthy control subjects were recruited.Four SNPs rs696217,rs26802,rs27647 and rs26311 were detected by the polymerase chain reaction-based-restriction fragment length polymorphism analysis.Results No significant differences in genotype or allele frequencies of the four SNPs were observed between schizophrenic patients and healthy controls (Pvalues of genotype frequencies were 0.649,0.944,0.410,0.826;P values of allele frequencies were 0.773,0.992,0.301,0.723).However,seven haplotypes(GAAG,GAGC,GAGG,GCGC,GCGG,TAGC,TAGG)showed significant differences in frequency between schizophrenic and control groups(P values were 0.011,0.001,1.76×10-6,9.84×10-10,1.38×10-9,2.12×10-5,2.57×10-6).Conclusion These data suggest that the GHRL gene may not be associated with susceptibility to schizophrenia in the Chinese Han population.However,the haplotype of GA may be the susceptive factor of schizophrenia.
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ObjectiveTo analyze the gene expression of neuregulin1 (Nrg1)mRNA and protein in encephalic region and peripheral blood,and to explore the consistency of the expression in central and peripheral in schizophrenia model rat induced by dizocilpine maleate ( MK801 ).Methods30 adult male SD rats were randomly divided into 3 groups ( 10 cases per group):model group injected with MK801 (0.6 mg/kg and 100μl/20 g)on the right rear of ventrolateral compartment,control group 1 ( no treatment) and control group 2 injected with equal volume normal saline.Nrg1 mRNA was measured in peripheral blood and in prefrontal lobe by using semiquantitative RT-PCR in 3 groups,and Nrg1 protein was measured in encephalic region (prefrontal lobe,dentate band and hippocamp) by using immunohistochemistry.ResultsThere was significant difference of the amount of Nrg1 mRNA among 3 groups (for center:F=9.141,P =0.001 ;for peripheral blood F =8.389,P =0.001 ),and it was higher in model group ( center:2.08 ± 0.64; peripheral blood:1.43 ± 0.46) than that in two control groups ( control group1,center:1.17 ± 0.42,peripheral blood:0.78 ± 0.39 ; control group 2,center:1.31 ± 0.44,peripheral blood:0.79 ± 0.37 ),but no statistical significant difference existed between two control groups.There was positive correlation of Nrg1 mRNA between center and periphery.There was significant difference of Nrg1 protein in prefrontal lobe,dentate band and hippocamp among 3 groups ( F value was 7.275,21.50 and 4.619,and P value was 0.003,0.000 and 0.019,respectively),and it was higher in model( 7.71 ± 2.55,11.67 ± 1.83and 10.18 ±2.08,respectively)than that in two control groups( control group 1:4.89 ± 1.06,7.53 ± 1.14 and 7.10 ± 2.52,respectively; control group 2:5.31 ± 1.39,8.10 ± 1.60 and 7.81 ± 2.50),but no statistical significant difference existed between two control groups.ConclusionMK801 can effect on the expression of Nrg1 gene,Nrg1 mRNA and protein increase in MK801 model rat,and the change is synchronous between center and periphery.