Objective Based on a clinical cohort study of repeated ketamine infusions for treatment-resistant depression(TRD),this study aimed to examine differences in brain-derived neurotrophic factor(BDNF)methylation among patients with varying therapeutic responses and explore its potential role in predicting treatment efficacy.Methods A retrospective analysis was conducted on peripheral plasma BDNF levels in 83 patients with TRD before and after a 2-week course of ketamine treatment(6 injections total).The Montgomery-Asberg depression rating scale(MADRS)was used to assess treatment efficacy.BDNF methylation levels were compared between responder group and non-responder group.The effect of methylation of the target CpG site on transcriptional activity was verified by using the dual luciferase reporter gene system.Results In patients with TRD who completed six repeated ketamine infusions,the responder group showed significant improvements compared to baseline levels in both MADRS scores(25.20±7.54 vs.8.10±5.32,P<0.01)and plasma BDNF concentrations[8.74(5.26,13.46)ng/mL vs.16.59(7.41,24.46)ng/mL,P<0.01].At baseline,35 CpG sites within the BDNF gene displayed significant methylation differences between response groups(P<0.05).Two CpG sites(rs1240718851 and cg06260077)located in the BDNF promoter region demonstrated a hypermethylation-low expression correlation,and dual-luciferase reporter assays confirmed that one of these sites functionally modulates BDNF expression.Conclusions The plasma BDNF concentration in TRD patients increases with the remission of depressive symptoms.The regulation of BDNF gene expression by methylation can predict the antidepressant efficacy of repeated intravenous ketamine.

Objective Based on a clinical cohort study of repeated ketamine infusions for treatment-resistant depression(TRD),this study aimed to examine differences in brain-derived neurotrophic factor(BDNF)methylation among patients with varying therapeutic responses and explore its potential role in predicting treatment efficacy.Methods A retrospective analysis was conducted on peripheral plasma BDNF levels in 83 patients with TRD before and after a 2-week course of ketamine treatment(6 injections total).The Montgomery-Asberg depression rating scale(MADRS)was used to assess treatment efficacy.BDNF methylation levels were compared between responder group and non-responder group.The effect of methylation of the target CpG site on transcriptional activity was verified by using the dual luciferase reporter gene system.Results In patients with TRD who completed six repeated ketamine infusions,the responder group showed significant improvements compared to baseline levels in both MADRS scores(25.20±7.54 vs.8.10±5.32,P<0.01)and plasma BDNF concentrations[8.74(5.26,13.46)ng/mL vs.16.59(7.41,24.46)ng/mL,P<0.01].At baseline,35 CpG sites within the BDNF gene displayed significant methylation differences between response groups(P<0.05).Two CpG sites(rs1240718851 and cg06260077)located in the BDNF promoter region demonstrated a hypermethylation-low expression correlation,and dual-luciferase reporter assays confirmed that one of these sites functionally modulates BDNF expression.Conclusions The plasma BDNF concentration in TRD patients increases with the remission of depressive symptoms.The regulation of BDNF gene expression by methylation can predict the antidepressant efficacy of repeated intravenous ketamine.

Objective To explore the correlation between the methylation level of 5-hydroxytryptamine receptor 1A(HTR1A) gene promoter region and severity of symptom in the manic epi-sode patients with bipolar disorder type Ⅰ(BD-Ⅰ). Methods Fifty six manic episode patients with BD-Ⅰand fifty nine healthy controls were randomly included in the study. The level of HTR1A gene promoter meth-ylation was measured with pyrosequencing technique in both manic episode patients with BD-Ⅰ and the healthy controls. The severity of symptoms was assessed with score of Bech-Rafaelsen Mania Rating Scale (BRMS) in patients with BD-Ⅰ. Pearson correlation analysis was employed to explore the correlation be-tween the serum level of HTR1A promoter methylation and score of BRMS in BD-Ⅰgroup. Results In-creased serum level of HTR1A gene promoter methylation was found in manic episode patients with BD-Ⅰ((66. 55±10. 55)%) compared with that in healthy controls((54. 03±8. 85)%)(P<0. 01). Positive corre-lation was found between the serum level of HTR1A gene promoter methylation and total score of BRMS in manic patient with BD-Ⅰ(r=0. 534,P<0. 01). Conclusion The current findings suggest that the serum level of HTR1A gene promoter methylation can be an epigenetic indicator for severity of manic symptom in BD-Ⅰ.

Objective To explore the influence factors of hyperarousal,personality characteristics and coping strategies on the vulnerability to stress-related sleep disturbance.Methods A total of 345 sleep good healthy volunteers were recruited bypurposive sampling technique.Every participant completed an extensive survey that included the general condition questionnaire,Ford Insomnia Response to Stress Test (FIRST),PreSleep Arousal Scale (PSAS),NEO Personality Inventory-Revised (NEOPI-R),Coping Inventory for Stressful Situations (CISS) and Heart Rate Variability(HRV).All participants were classified as High risk group andLow risk group by using the FIRST criterion.Results The high risk group was younger than the low risk group (27.91±8.22 vs 24.82±7.73,P＜0.01),and had a higher percentage of females (34.7％ vs 53.4％,P＜0.05).The high risk group showed significantly higher scores in PSAS total (30.11±6.22),pesleep cognitive arousal (17.73± 4.51),presleep somatic arousal (12.78 ± 3.23),neuroticism (3.13 ± 0.51),emotion oriented (48.98 ± 10.54),but lower score in extraversion (2.96±0.54),then those indicators of the low risk group (28.52±5.82,16.32±4.32,11.41±2.75; 3.11±0.56,2.87±0.47,46.23±11.21,3.11±0.56,P＜0.01 or 0.05).There were significant difference between the two group in LF/HF (1.51 ±0.19 vs 1.17±0.11,P＜0.01),HF((311.21 ±72.32) ms2/Hz vs (490.43 ± 91.74)ms2/Hz,P＜0.01),LF((469.49±85.67)ms2/Hzvs (573.21±98.75) ms2/Hz,P＜0.01) in HRV.Results of linear regression analysis showed that gender,and scores of PSAS total,cognitive arousal,presleep cognitive arousal,presleep somatic arousal,neuroticism,emotion oriented and LF/HF were significant correlation with FIRST score (P＜0.01 or 0.05).Conclusion Presleep cognitive and somatic arousal,neurotic character may be the premorbid characteristics of stress-related sleep disturbance,and bad stress coping strategies are easy to promote the development of insomnia.

ObjectiveTo investigate the association of phosphorylation of mammalian target protein of rapamycin (pmTOR) expression with glioma malignancy grades,and the correlation of pmTOR expression with Survivin and Ki-67,which represent tumor cell anti-apoptosis ability and reproductive activity.MethodsImmunohistochemistry EliVision method was employed to detect the expression of pmTOR,Survivin and Ki-67 in paraffin tissues from 87 patients with glioma (grade Ⅰ - Ⅱ 27 cases,grade Ⅲ24 cases and grade Ⅳ 36 cases).The association between positive expression rate,level of pmTOR and malignancy grades,and the correlation of its expression level with Survivin and Ki-67 were further evaluated.Results There was no significant difference in the positive expression rate of pmTOR among grade Ⅰ - Ⅱ(77.8％,21/27),grade Ⅲ(75.0％,18/24) and grade Ⅳ (72.2％,23/36) (P ＞ 0.05).However,the significant association between pmTOR expression level and malignancy grades was observed.The expression from 87 patients with glioma was significantly positively correlated with Survivin and Ki-67 expression level (r =0.858,P ＜ 0.01 ;r =0.708,P ＜ 0.01 ).ConclusionsThe expression level of pmTOR is associated with malignancy grades,tumor cell anti-apoptosis ability and reproductive activity.pmTOR may be served as a useful marker for predicting the biological behavior of glioma and a useful target for gene therapy.

Objective To detect the c fos proto oncogene expression in the hypothalamus of the mice which underwent water immersion and the effects of propofol Methods Twenty four mice were divided randomly into three groups:group A (normal control), group B (water immersion) and group C (water immersion+propofol) The group C was subdivided into two sub groups: in group C1 3mg/kg propofol was administered intraperitoneally 10min after water immersion; in group C2 3mg/kg propofol was given intraperitoneally 10min before water immersion The cerebral c fos positive cells were detected by S P immunohistochemical assay and the gastric ulcer index was calculated using Guth method Results Animal in group A had no gastric mucosa injury The gastric ulcer index increased significantly (6 2?2 1) with the obvious bleeding points in gastric mucosa and the rate of c fos gene positive cell increased markedly (64 2%?2 1%) in group B as compared with those in group A The gastric ulcer index and c fos gene expression rate decreased greatly in group C1 (3 2?1 0, 21 8%?3 2%) and group C2 (2 1?0 9, 18 4%?3 5%) respectively (P