Objective:To explore the effect of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive behavioral therapies (CBT) on the cognitive function and alcohol craving in patients with alcohol dependence.Methods:From March 2019 to September 2021, a total of 150 patients with alcohol dependence were enrolled and randomly divided into rTMS treatment group (rTMS+ sham CBT, n=41), CBT treatment group (CBT+ sham rTMS, n=34), rTMS+ CBT treatment group( n=36) and control group (sham rTMS+ sham CBT, n=39). At baseline (before treatment), 2nd week, 8th week, 12th week and 24th week, alcohol dependence scale (ADS) was used to evaluate the degree of alcohol dependence, the obsessive compulsive drinking scale (OCDS) was used to assess patients' drinking craving, and Montreal cognitive assessment scale (MoCA) was used to assess the overall cognitive level of patients.SPSS 23.0 statistical software was used to compare the differences of ADS, OCDS and MoCA scale scores of the four groups by repeated measure ANOVA and simple effect analysis. Results:(1)The patients in the four groups were evaluated with ADS scale at baseline, 12th week and 24th week respectively.The interaction of group×time( F=1.279, P=0.279) and the main effect of group were not significant ( F=0.882, P=0.454), and the main effect of time was significant ( F=12.925, P<0.001) .Further simple effect analysis showed that the ADS score of rTMS+ CBT group was lower than that of baseline(14.48±5.70, 10.00±6.51) ( P=0.01) at 24th week.(2)Patients in the four groups were assessed with OCDs scale at baseline, 2nd week, 8th week, 12th week and 24th week, and the interaction of group×time was significant ( F=2.015, P=0.042). Further simple effect analysis showed that the OCDs scores of rTMS group and rTMS+ CBT group at each follow-up time node were lower than those at baseline period (all P<0.05). (3)Patients in the four groups were assessed with MoCA scale at baseline, 8th week, 12th week and 24th week, and the interaction of group×time was not significant ( F=1.660, P=0.106), and the main effect of group and the main effect of time were significant ( F=2.964, P=0.038; F=14.239, P<0.001). Further simple effect analysis showed that the score of MoCA scale in CBT group at the 24th week was higher than that at baseline (21.73±5.81, 24.60±3.98)( P=0.029), the score of MoCA scale in rTMS+ CBT group at the 24th week was higher than that at the 8th week (23.50±6.01, 25.95±2.87) ( P=0.006), and the score of MoCA scale in rTMS group at the 12th week was higher than that in control group (22.08±6.64, 26.64±2.46)( P=0.009). Conclusion:rTMS combined with CBT can be effective in improving alcohol craving and cognitive function in patients with alcohol dependence, and has a good long-term effect.

Objective:To observe the effect of ganglioside (GM1) on the expression of Caspase-3, Bax and Bcl-2 in hippocampus of mice with chronic alcoholism.Methods:Forty male Balb/c mice were randomly allocated into chronic alcoholism group ( n=10), control group ( n=10), low dose GM1 treatment group ( n=10) and high dose GM1 treatment group ( n=10). The mouse model of chronic alcoholism was established by intragastric administration of alcohol in the chronic alcoholism group (the concentration of alcohol solution gradually increased from 5% to 35%), mice in the control group were given the same amount of normal saline, while those in the low and high dose treatment groups were given intraperitoneal injection of GM1 (10, 30 mg/kg per day) after intragastric administration of alcohol. Four weeks after oral administration, alcohol preference test and behavior test were performed to determine the expression levels of Caspase-3, Bax and Bcl-2 in hippocampus. One-way ANOVA was used for comparison between groups, and Bonferroni method was used for pairwise comparison. Results:There were significant differences of alcohol consumption rate among the four groups ( F=630.83， P<0.05).The consumption rate of control group (18.9%±2.2%) and high dose GM1 treatment group (50.9%±3.2%) was lower than that of chronic alcoholism group (56.5%±3.0%).Similarly, there were also significant differences of behavior test result among the four groups ( F=379.52, 7001.18, 33.87, 305.06, all P<0.05). The results in chronic alcoholism group were lower than that of control group, and high dose GM1 treatment group were better than those in chronic alcoholism group ( P<0.05). Results of Western Blot showed that there were significant differences in the expression of Caspase-3, Bax and Bcl-2 proteins among the four groups ( F=12.42, 14.07, 242.37, all P<0.05). Compared to chronic alcoholism group, the expression of Caspase-3 protein and Bax protein in hippocampus of control group and high dose GM1 treatment group decreased significantly, while the expression level of Bcl-2 protein in hippocampus of control group, high dose GM1 treatment group and low dose GM1 treatment group was significantly higher than that of chronic alcohol intoxication group ( P<0.05). Conclusions:Gangliosides can decrease the expression of Caspase-3 and Bax protein in the hippocampus of chronic alcoholism mice, and increase the expression of Bcl-2 protein.

Objective:To observe the effect of ganglioside (GM1) on the expression of Caspase-3, Bax and Bcl-2 in hippocampus of mice with chronic alcoholism.Methods:Forty male Balb/c mice were randomly allocated into chronic alcoholism group ( n=10), control group ( n=10), low dose GM1 treatment group ( n=10) and high dose GM1 treatment group ( n=10). The mouse model of chronic alcoholism was established by intragastric administration of alcohol in the chronic alcoholism group (the concentration of alcohol solution gradually increased from 5% to 35%), mice in the control group were given the same amount of normal saline, while those in the low and high dose treatment groups were given intraperitoneal injection of GM1 (10, 30 mg/kg per day) after intragastric administration of alcohol. Four weeks after oral administration, alcohol preference test and behavior test were performed to determine the expression levels of Caspase-3, Bax and Bcl-2 in hippocampus. One-way ANOVA was used for comparison between groups, and Bonferroni method was used for pairwise comparison. Results:There were significant differences of alcohol consumption rate among the four groups ( F=630.83， P<0.05).The consumption rate of control group (18.9%±2.2%) and high dose GM1 treatment group (50.9%±3.2%) was lower than that of chronic alcoholism group (56.5%±3.0%).Similarly, there were also significant differences of behavior test result among the four groups ( F=379.52, 7001.18, 33.87, 305.06, all P<0.05). The results in chronic alcoholism group were lower than that of control group, and high dose GM1 treatment group were better than those in chronic alcoholism group ( P<0.05). Results of Western Blot showed that there were significant differences in the expression of Caspase-3, Bax and Bcl-2 proteins among the four groups ( F=12.42, 14.07, 242.37, all P<0.05). Compared to chronic alcoholism group, the expression of Caspase-3 protein and Bax protein in hippocampus of control group and high dose GM1 treatment group decreased significantly, while the expression level of Bcl-2 protein in hippocampus of control group, high dose GM1 treatment group and low dose GM1 treatment group was significantly higher than that of chronic alcohol intoxication group ( P<0.05). Conclusions:Gangliosides can decrease the expression of Caspase-3 and Bax protein in the hippocampus of chronic alcoholism mice, and increase the expression of Bcl-2 protein.