OBJECTIVE To explore the biological processes and pathways associated with memory function which may be regulated by gene promoter methylation. METHODS The genome-wide promoter methylation statuses in 9 healthy individuals were analyzed with a Multiplex HG18 CpG Promoter chip. Genes with promoter methylation statuses strongly correlated with both immediate and delayed visual memory function were preceded for pathway and physical interactions analysis. RESULTS Sixty nine genes have been correlated with both immediate and delayed visual memory functions. Twenty two pathways, with a Q-value of < 0.05, were identified by the pathway and physical interactions analysis, which included energy metabolism, axon guidance, tyrosine kinase activity, anterograde synaptic vesicle transport, and leukocyte migration and differentiation. CONCLUSION Pathways related with memory function may be regulated by DNA methylation.
Adolescent ; Adult ; DNA Methylation ; Female ; Humans ; Male ; Memory ; Promoter Regions, Genetic ; Signal Transduction ; physiology

OBJECTIVETo investigate the effect of risperidone, an antipsychotic drug, on the Akt-GSK3β pathway and the role of PI3K in dopamine D2 receptor (DRD2) expression and Akt-GSK3β signal pathway.

METHODSHuman glioma cells (U251) were cultured in vitro. Cells without any treatment as control, Western blotting was used for measuring the expression of Akt (Thr308 and Ser473) and GSK3β (Ser9) protein phosphorylation by risperidone and LY294002 in U251 cell, and real-time PCR was used for detecting the expression of DRD2 mRNA.

RESULTSRisperidone has significantly enhanced the expression of phosphorylated Akt and phosphorylated GSK3β (P< 0.05), but did not alter the mRNA expression of DRD2. LY294002 could reduce the phosphorylation of Akt and GSK3β (P< 0.01, P< 0.05), and also decrease the DRD2 mRNA (P<0 .05).

CONCLUSIONRisperidone can activate the Akt-GSK3β signaling pathway in the U251 cells, and PI3K is a common regulatory site in Akt-GSK3β signaling and D2 receptor gene expression.

Antipsychotic Agents ; pharmacology ; Cell Line, Tumor ; Glioma ; drug therapy ; genetics ; metabolism ; Glycogen Synthase Kinase 3 ; genetics ; metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Risperidone ; pharmacology ; Signal Transduction ; drug effects

Objective To investigate the effects of CD226 knockout ( KO) on obese mice fed with high fat diet and to analyze the composition of immune cells in CD226KO obese mice for further elucidating the immunological mechanism of CD226 involved in high fat diet-induced obesity. Methods Both wild-type ( WT) and CD226KO mice were randomly divided into two groups, high-fat and normal diet groups, and fed for 14 weeks to establish the type 2 diabetes model. Immune cells in mouse spleen and peripheral blood were analyzed by flow cytometry. In in vitro experiments, NK92-MI cells were infected with pshRNA-CD226 lenti-virus to silence CD226 expression, and then qPCR was performed to detect the expression of Foxp3, TNF-αand IFN-γ at mRNA level. Results In the high-fat diet groups, CD226KO mice had lower blood glucose, serum insulin and HOMA-IR than WT mice, but higher HOMA-IS and HOMA-β. CD226KO could reduce compensatory hyperplasia of islet tissue, and significantly down-regulate the proportion of spleen NK cells in mice. The proportion of CD3-CD49b+CD25+Foxp3+regulatory NK cells (NKreg) increased significantly in CD226KO mice. CD226KO could significantly increase Foxp3 expression in NK92-MI cells and decrease the expression of TNF-α and IFN-γ. Conclusions CD226KO can alleviate insulin resistance, increase the number of islet β-cell and improve islet β-cell function in obese mice. The mechanism might be related to the up-regulation of Foxp3+ NKreg ratio.

OBJECTIVE: To explore the correlation between altered levels of neurotransmitters in the frontal lobe and hippocampus and behavioral abnormalities in a Clock variant mice modeling bipolar disorder manic disorder. METHODS: Open field test and Elevated plus-maze test were carried out on the Clock mutant and wild-type control groups. The frontal lobe and hippocampus of Clock mutant mice and controls were dissected, and neurotransmitters in tissue extracts were analyzed by high-performance liquid chromatography and mass spectrometry. The concentration of neurotransmitters and behavioral indicators were assessed by t test and Pearson correlation analysis using SPSS 22.0. RESULTS: The Clock mutant mice showed a significant increase in activity, albeit with no difference in the level of anxiety from the wild-type controls, which suggested that the Clock mutant mice can be used as a model for manic attack of bipolar disorder. Altered neurotransmitter levels were detected in the frontal and hippocampal regions, including elevated histamine in the left hippocampus, reduced histamine in the right hippocampus, reduced gamma-aminobutyric acid (GABA) in bilateral hippocampus, elevated dihydroxyphenylalanine (DOPA) in the left frontal lobe and reduced DOPA in the right hippocampus, and decreased glutamine in bilateral frontal lobes. The reduced glutamine in the left frontal lobe and GABA in the right hippocampus correlated with the increased activity of Clock mutant mice. CONCLUSION Clock mutant mice showed abnormal behavior with increased activity. Reduced glutamine in the left frontal lobe and GABA in the right hippocampus were correlated with increased activity.

Humans ; Depressive Disorder, Major ; Motor Cortex ; Magnetic Resonance Imaging

This study was aimed to analyze the application of non-pharmacotherapy in treating cervical radiculopathy (CR) in real-world,and to provide clinical reference for CR non-pharmacotherapy.The clinical real-world data of CR was extracted by using information sharing system of traditional Chinese medicine (TCM) and clinical research.Six hundred and twenty-eight inpatients and outpatients with CR were enrolled from December 2012 to July 2014 in the information system database of Wangjing Hospital.Basic characteristics of the non-pharmacotherapy groups were analyzed by statistical description method.The node degree and mutual information value were recorded for non-pharmacotherapy application of all patients by using liquorice software.Complex network diagrams were generated.The results showed that 47％ of CR patients received non-pharmacotherapy (294/628),including 67 males and 227 females.The average age of patients was 49 years old,and the prevalence of the disease was the highest from 45 to 65 years old.In all patients,the usage of manipulation and cervical traction was higher,and the combination of manipulation and acupuncture was the most.Within outpatients,the proportion of cervical traction was higher,and the combination of manipulation and acupuncture was the most frequently.Within inpatients,the proportion of manipulation and cervical traction was higher,and the combination of comprehensive physical therapy and exercise therapy was the most frequently.It was concluded that non-pharmacotherapy has been commonly used in clinical treatment of CR.Cervical traction and manipulation was the widest applications.The combination treatment was in wide application.Future studies should increase the sample size of CR patients from different regions,and enhance gradually the level of evidence of clinical research for non-pharmacotherapy treating CR.

Objective:To investigate the influencing factors of textbook outcomes in liver surgery (TOLS) after radical resection of gallbladder carcinoma.Methods:The retrospective case-control study was conducted. The clinicopathological data of 530 patients who underwent radical resection of gallbladder carcinoma in 15 medical centers, including the First Affiliated Hospital of Army Medical University et al, from January 2014 to January 2020 were collected. There were 209 males and 321 females, aged (61±10)years. Patients underwent radical resection of gallbladder carcinoma, including cholecystectomy, hepatectomy, invasive bile duct resection, and lymph node dissection. Observation indicators: (1) situations of TOLS; (2) influencing factors of TOLS. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. The univariate analysis was conducted using the corresponding statistical methods based on data type, and variables with P<0.10 were included in multivariate analysis. Multivariate analysis was conducted using the Logistic stepwise regression model. Results:(1) Situations of TOLS. All 530 patients underwent radical resection of gallbladder carcinoma, and there were 498 cases achieving R 0 resection, 508 cases without ≥grade 2 intra-operative adverse events, 456 cases without postoperative grade B and grade C biliary leakage, 513 cases without postoperative grade B and grade C liver failure, 395 cases without severe com-plications within postoperative 90 days, 501 cases did not being re-admission caused by severe com-plications within postoperative 90 days. Of the 530 patients, 54.53%(289/530) of patients achieved postoperative TOLS, while 45.47%(241/530) of patients did not achieve postoperative TOLS. (2) Influencing factors of TOLS. Results of multivariate analysis showed that American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy were independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma ( odds ratio=2.65, 1.87, 5.67, 5.65, 2.55, 3.34, 95% confidence interval as 1.22?5.72, 1.18?2.95, 2.51?12.82, 2.83?11.27, 1.41?4.63, 1.88?5.92, P<0.05). Conclusion:American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy are independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma.

BackgroundThere exist differences in the subjective and objective cognitive functions of patients with depressive disorder， ane there are limited research on influencing factors of such phenomenon currently. ObjectiveTo explore the differences in subjective and objective cognitive function in patients with depressive disorder as well as influencing factors， and to provide references for further understanding of cognitive impairment in patients with depressive disorder. MethodsA total of 77 patients with depressive disorder who received outpatient or inpatient treatment in the Fourth People's Hospital of Chengdu from January 13， 2022 to December 11， 2023 were selected for the study. These patients also met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders， fifth edition（DSM-5）. Various tools were employed to assess patients in this study： Montgomery-Asberg Depression Rating Scale （MADRS） for the depressive symptoms， Perceived Deficits Questionnaire for Depression （PDQ-D） and Chinese Version of Brief Neurocognitive Test Battery （C-BCT） for the subjective and objective cognitive function， Sheehan Disability Scale （SDS） for the social function， and Clinical Global Impression-Severity of Illness（CGI-SI） for the severity of patient's condition. Pearson correlation analysis was used to examine the correlation of subjective and objective cognitive function and their differences with age， years of education， MADRS total score， SDS total score， and CGI-SI score. Multiple linear regression was used to explore the influencing factors of the differences between subjective and objective cognitive function. ResultsThere was a statistically significant difference in the total PDQ-D scores and the difference of subjective and objective cognitive function （D value） between depressive patients with and without medication （t=-4.228， -2.392， P<0.05 or 0.01）. There was no statistically significant correlation in subjective and objective cognitive function in patients with depressive disorder （r=-0.148， P>0.05）. Negative correlations can be observed between the PDQ-D total score and age or years of education （r=-0.333， -0.369， P<0.01）. The PDQ-D total score was positively correlated with MADRS total score， SDS total score and CGI-SI score （r=0.487， 0.637， 0.434， P<0.01）. D value was negatively correlated with age and years of education （r=-0.411， -0.362， P<0.01）， while positively correlated with MADRS total score， SDS total score and CGI-SI score （r=0.259， 0.468， 0.299， P<0.05 or 0.01）. Age （β=-0.328， P<0.01） and SDS total score （β=0.409， P<0.01） were two predictive factors for D value. ConclusionThe difference between subjective and objective cognitive function among patients with depressive disorder is related to several factors including age， years of education， severity of symptoms and impairment of social function. ［Funded by Surface Project of National Natural Science Foundation of China （number， 62173069）； Technological Innovation 2030-Major Project of "Brain Science and Brain-Like Research" （number， 2022ZD0211700）； Key R&D Support Program and Major Application Demonstration Project of Chengdu Science and Technology Bureau （number， 2022-YF09-00023-SN）］