Pachymic acid protects against Crohn's disease-like intestinal barrier injury and colitis in miceby suppressingintestinal epithelial cell apoptosis via inhibiting PI3K/AKT signaling / 南方医科大学学报

OBJECTIVE@#To investigate the effect of pachymic acid (PA) against TNBS-induced Crohn's disease (CD)-like colitis in mice and explore the possible mechanism.@*METHODS@#Twenty-four C57BL/6J mice were randomized equally into control group, TNBS-induced colitis model group and PA treatment group. PA treatment was administered via intraperitoneal injection at the daily dose of 5 mg/kg for 7 days, and the mice in the control and model groups were treated with saline. After the treatments, the mice were euthanized for examination of the disease activity index (DAI) of colitis, body weight changes, colon length, intestinal inflammation, intestinal barrier function and apoptosis of intestinal epithelial cells, and the expressions of TNF-α, IL-6 and IL-1β in the colonic mucosa were detected using ELISA. The possible treatment targets of PA in CD were predicted by network pharmacology. String platform and Cytoscape 3.7.2 software were used to construct the protein-protein interaction (PPI) network. David database was used to analyze the GO function and KEGG pathway; The phosphorylation of PI3K/AKT in the colonic mucosal was detected with Western blotting.@*RESULTS@#PA significantly alleviated colitis in TNBS-treated mice as shown by improvements in the DAI, body weight loss, colon length, and histological inflammation score and lowered levels of TNF-α, IL-6 and IL-1β. PA treatment also significantly improved FITC-dextran permeability, serum I-FABP level and colonic transepithelial electrical resistance, and inhibited apoptosis of the intestinal epithelial cells in TNBS-treated mice. A total of 248 intersection targets were identified between PA and CD, and the core targets included EGFR, HRAS, SRC, MMP9, STAT3, AKT1, CASP3, ALB, HSP90AA1 and HIF1A. GO and KEGG analysis showed that PA negatively regulated apoptosis in close relation with PI3K/AKT signaling. Molecular docking showed that PA had a strong binding ability with AKT1, ALB, EGFR, HSP90AA1, SRC and STAT3. In TNBS-treated mice, PA significantly decreased p-PI3K and p-AKT expressions in the colonic mucosa.@*CONCLUSION@#PA ameliorates TNBS-induced intestinal barrier injury in mice by antagonizing apoptosis of intestinal epithelial cells possibly by inhibiting PI3K/AKT signaling.

Relationship between disrupted-in-schizophrinia-1 polymorphism and the abnormal brain structure in childhood and adolescence with schizophrenia / 中华实用儿科临床杂志

Objective:To investigate the relationships of rs4658971 polymorphism of disrupted-in-schizophrinia-1 ( DISC1) gene with schizophrenia in children and adolescents and with the brain structure of such patients. Methods:(1) A total of 577 children and adolescents with schizophrenia were recruited from the Inpatient Department of the Second Affiliated Hospital of Xinxiang Medical University from October 2010 to December 2018, and 516 healthy children were selected as the control group.The rs4658971 polymorphism of DISC1 gene was detected by restriction fragment length polymorphism (PCR-RFLP). The differences of DISC1 genotype and allele frequencies between schizophrenia patients and healthy children were compared by Chi-square test.(2)One hundred and eighteen patients with the first-episode schizophrenia whose illness duration was no more than 12 months and 101 healthy children and adolescents were detected by 3.0T magnetic resonance imaging (MRI). The craniocerebral structures of patients with different DISC1 genotypes were analyzed by covariance with age as the covariant. Results:(1) The rs4658971 genotype frequencies(TT 6.6% vs.5.2%, TC 37.4% vs.38.4%, CC 56.0% vs.56.4%, χ2=0.91, P=0.63) and allele frequencies(C 74.70% vs.75.58%, T 25.30% vs.24.42%, χ2=0.23, P=0.63) of DISC1 gene in children and adolescents with schizophrenia were not significantly different from those in the healthy children.(2) Compared with the control group, the transverse diameter of the third ventricle was significantly enlarged in children and adolescent with schizophrenia [(4.68±1.41) mm vs.(4.06±1.36) mm, F=8.534, P=0.004], while the distance between the anterior feet of the lateral ventricle, the width of the caudate nucleus head and the thickness of the hippocampus were significantly reduced [(30.69±2.51) mm vs.(32.02±2.41) mm, (8.17±1.01) mm vs.(9.22±1.14) mm, (8.93±0.97) mm vs.(9.93±1.14) mm], and the differences were statistically significant( F=15.435, 40.201, 44.650, all P<0.001). The covariance analysis (with age as the covariant) showed that there was significant difference in the width of the caudate nucleus head between patients with CC genotype and those with CT+ TT genotype[(8.73±0.85) mm vs.(7.39±0.61) mm, F=41.376, P<0.001]. Conclusions:There are multiple brain structural changes in children and adolescents with first-episode schizophrenia.T allele carriers of DISC1 gene rs4658971 locus may be related to the reduced width of the caudate nucleus head in patients.

The correlation between the volume of brain white matter and cognitive function in childhood and adolescence-onset schizophrenia / 中华行为医学与脑科学杂志

Objective To investigate the relationship between brain white matter volume (WMV) and cognitive function (CF) in childhood and adolescence-onset schizophrenia (CAOS).Methods Forty childhood and adolescence-onset first-episode schizophrenia patients (case group) and thirty-nine healthy volunteers (control group) were selected.All subjects underwent a 3.0 T magnetic resonance imaging(MRI) scans for data acquisition.The Chinese version of MATRICS consensus cognitive battery(MCCB) was used to assess the cognitive function.The psychiatric symptoms of schizophrenia were assessed with the positive and negative syndrome scale (PANSS).And t test was applied to compare whether there were differences in WMV,CF between the two groups.Pearson correlation analysis was used to analyze whether the differences were related with cognitive function and mental symptoms.Results Compared with healthy controls,the case group exhibited WMV deficits in the region of left frontal lobe (LFL) (MNI:x =-27,y =12,z =21),right side limbic lobe (RSLL) (MNI:x =18,y =-9,z =39) and left cingulate gyrus (LCG) (MNI:x =-21,y =-18,z=45) (P＜0.05).The WMV of LFL was negatively related with the total score (r=-0.344,P＜0.05) and the WMV of LCG was negatively related with the positive symptoms score (r=-0.326,P＜0.05) and total score (r=-0.348,P＜0.05) of the PANSS.Besides,compared with the controls,the patients showed significant increase in the scores of Trail Making Test (t =3.56,P＜ 0.01),while significant decrease in the scores of the HVLT-R and BVMT-R(t=-5.67,-8.66,P＜0.05).The WMV of RSLL was positively correlated with verbal fluency test in the case group (r=0.40,P＜0.05).Conclusion CAOS patients exist multiple reduced WMV and cognitive impairment,suggesting the importance of the WMV abnormalities in the pathophysiological mechanism of cognitive impairment.

Relationship between function and resting state functional magnetic resonance imaging amplitude of low-frequency fluctuations in childhood and adolescence-first-onset obsessive-compulsive disorder / 中华实用儿科临床杂志

Objective To investigate the characteristics and relationship of cognitive function and resting state functional magnetic resonance imaging(fMRI) amplitude of low-frequency fluctuations (ALFF)in childhood and adolescence-first-onset obsessive-compulsive disorder(OCD).Methods Twenty-four childhood and adolescence-first-onset OCD patients (patient group) and thirty-three age/gender/education-matched healthy controls (healthy control group) were enrolled in this study.The participants' cognitive function was tested with trail making test (TMT),symbol coding,Hopkins verbal learning test-revised (HVLT-R),brief visuospatial memory test-revised (BVMT-R),verbal fluency test (VF),digital span test,maze test and Stroop test.Then a resting-state fMRI scan was conducted for each participant.Amplitude of low-frequency fluctuation approach was used to explore the differences of resting-state brain function between patients and controls,and analyze the significant brain regions by adopting t test.The cognitive functions of patients and healthy control group in the significant brain regions were compared by using Pearson correlation analysis.Results The patient group had lower scores than healthy control group in symbol coding,BVMT-R and digital span test,and the differences were statistically significant [(45.24 ± 10.32)scores vs.(56.85 ± 9.57) scores,(21.94 ± 6.99) scores vs.(30.58 ± 3.92) scores,(64.06 ± 20.00) scores vs.(78.03 ±18.08) scores;t =3.96,4.90,2.50;all P ＜ 0.05].Corrected by Alphasim,patient group showed significantly increased ALFF in the left and fight temporal lobe,left and fight posterior lobe of cerebellum,right middle temporal gyrus,but ALFF decreased in the area of left and right lenticula,left putamen compared with the healthy control group (all P ＜ 0.05).The patients group showed that TMT scores were positively correlated with the value of ALFF in the right temporal lobe (r =0.67),and color scores were positively correlated with the value of ALFF in the right middle temporal gyrus (r =0.53),but colour scores were negatively correlated with the value of ALFF in the right tcmporal lobe (r =-0.54);the healthy control group showed that BVMT-R and digital span test scores were positively correlated with the value of ALFF in the left temporal lobe (r =0.47,0.41),but digital span test scores were negatively correlated with the value of ALFF in the right temporal lobe (r =-0.49),and colour scores were negatively correlated with the value of ALFF in the left temporal lobe (r =-0.35),while word and color-word scores were negatively correlated with the value of ALFF in the right middle temporal gyrus (r =-0.39,-0.36);the correlation coefficient above had statistical significance (all P ＜ 0.05).Conclusions The childhood and adolescence-first-onset OCD patients had cognitive impairment,including speed of processing,visual learning and memory,working memory;and the patients showed abnormal spontaneous neural activity at some brain regions.The cognitive dysfunction may be associated with abnormal spontaneous neuronal activity in childhood and adolescence-first-onset OCD.

Behavior characteristics and cognitive function in the first-episode children with or without obsessive-com-pulsive symptoms / 中国神经精神疾病杂志

Objective To investigate cognitive function and behavior characteristics in the childhood onset schizo?phrenia patients with or without obsessive-compulsive symptoms. Methods One hundred forty-nine schizophrenia chil?dren were recruited and 72 healthy children served as children control group. According to the Schedule for Affective Dis?orders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), the patients were fur?ther divided into two groups, the children with obsessive-compulsive disorder group (70 cases) and the children without obsessive-compulsive disorder group (79 cases). All the children were retrospectively surveyed and the Achenbach’s Child Behavior Check-list (CBCL) was used to assess their social competence and behavioral characteristics at the age from 6-year-old to 10-year-old. The cognitive function was estimated with WISC, STROOP color and word test, trail making test, visal spatial memory test and maze test. Results Compare to the control group, the CBCL factor scores of behavior problems were higher (P<0.01), social ability factor scores were lower (P<0.05) and all factor scores in the cog?nitive function tests were lower (P<0.05) in the two patients groups. Compare to the patients without obsessive-compul?sive symptoms, the CBCL factor scores of the school situation (P<0.01), splitting force (P<0.01), and physical complaints (P<0.01) were significantly higher and the scores were significantly lower in the test of common sense (P<0.01), wood (P<0.01), STROOP (P<0.01) and BVMT-R (P<0.01) in those with obsessive-compulsive symptoms. Correlation analysis showed that social competence total scores were positively correlated with similarity in the patients with obsessive-com?pulsive symptoms (r=0.31, P<0.01);while behavior problems total scores were negatively correlated with wood (r=-0.31, P<0.01) and patchwork (r=-0.32, P<0.01) in the patients without obsessive-compulsive symptoms. Conclusion The schizophrenia children with obsessive-compulsive symptoms have more behavioral problems in pre-symptom period and their cognitive dysfunction are more severe following onset of the disease. Cognitive function is related to behavioral prob?lems and social competence in the schizophrenia children with or without obsessive-compulsive symptoms .