Objective To observe the changes of myelin sheath in corpus callosum on non-ischemic side after ischemic stroke in rats with cerebral ischemia/reperfusion(I/R)model,and to investigate the effect of vagus nerve stimulation(VNS)on secondary demyelination in I/R model.Methods Forty-two rats were randomly assigned to sham,I/R,or I/R+VNS groups,with 14 rats in each group.Except for the sham group,the rats in other groups were used to construct I/R model by a middle cerebral artery occlusion thread method.In addition,the rats in the I/R+VNS group were given repetitive electrical stimulation of the left vagus nerve for 60 min at 30 min after ischemia occlusion.The cerebral infarction volume was observed by 2,3,5-triphenyltetrazolium chloride staining.The expression levels of myelin basic protein(MBP)and myelin-associated glycoprotein(MAG)in the corpus callosum on the non-ischemic side were detected by Western blotting.The integrity and thickness of myelin sheaths in the corpus callosum on the non-ischemic side were observed by Luxol fast blue staining and transmission electron microscopy,respectively.Results Compared with the sham group,the volume of cerebral infarction in the I/R group was increased(P＜0.01).On the 3rd day after I/R,compared with the sham group,the expression levels of MBP and MAG were significantly decreased(both P＜0.01),the intensity of Luxol fast blue staining was significantly decreased(P＜0.01),and the thickness of the myelin sheath was significantly thinner(g-ratio was increased,P＜0.01)in the corpus callosum on the non-ischemic side.Compared with the I/R group,the expression levels of MBP and MAG in the I/R+VNS group were significantly increased(both P＜0.05),the intensity of Luxol fast blue staining was significantly increased(P＜0.01),and the thickness of myelin sheath was significantly increased(g-ratio was decreased,P＜0.01)in the corpus callosum on the non-ischemic side.Conclusion Secondary demyelination occurs on the non-ischemic side of the rat corpus callosum after ischemic stroke,and VNS can ameliorate the demyelination.

Objective To explore the abnormality of top-down and bottom-up attention patterns in patients suffering from coronary heart disease(CHD)patients with heart-qi deficiency syndrome based on the theory of"five spirits".Methods From July 2024 to December 2024,30 CHD patients with heart-qi deficiency syndrome were recruited,and 30 subjects without CHD as the control group according to the principle of matching age,sex and years of education.Two groups of subjects were tested with top-down and bottom-up spatial cueing paradigm.Results Compared with the control group,CHD patients with heart-qi deficiency syndrome had longer valid reaction time(vRT)and lower average reaction time difference value(△RT)in top-down test(P＜0.05),and longer vSRT in bottom-up test.Correlation analysis showed that heart-qi deficiency syndrome score was positively correlated with top-down test indexes invalid reaction time(ivRT)(P＜0.05),negatively correlated with △RT(P＜0.01)and valid accurany(vAC)(P＜0.05).It was positively correlated with valid long reaction time(vLRT)(P＜0.01)and invalid long reaction time(ivLRT)(P＜0.01).Generalized linear model analysis showed that non-CHD subjects had shorter vRT(P＜0.01)and larger △ RT(P＜0.05)than CHD patients for top-down test.For bottom-up tests,non-CHD subjects had shorter vSRT than CHD patients(P＜0.05).Conclusion The change of top-down and bottom-up attention patterns in CHD patients with heart-qi deficiency syndrome provides a modern neuropsychological basis for the theory of"heart stores spirits".

Objective To analyze the core syndromes of patients with generalized anxiety disorder(GAD),explore the core pathogenesis,and offer innovative perspectives and practical strategies for the traditional Chinese medicine(TCM)diagnosis and treatment of GAD.Methods The basic information of GAD patients was collected,and depression symptoms were evaluated with Hamilton Anxiety Scale to evaluate anxiety symptoms,Hamilton Depression Scale,and the TCM psychiatric and somatic symptoms were evaluated with Traditional Chinese Medicine Symptom Observation Form.Based on the data collected from the Traditional Chinese Medicine symptom observation table,the systematic clustering method was used to cluster the symptoms with a frequency greater than 10％,determine the disease type syndrome and disease location syndrome,and form a syndrome symptom relationship table.According to this table,the traditional Chinese medicine syndrome score of each patient is calculated.The complex network analysis was carried out to evaluate core syndromes and analyze the relationships between core syndromes and psychiatric symptoms and core syndromes and other syndromes.Results A total of 517 patients with GAD were included.There were 81 symptoms with a frequency of more than 10％,including 21 psychological symptoms and 60 physical symptoms.The clustering analysis led to a total of 12 syndromes,including 6 pathological syndromes,namely yin deficiency,heat,phlegm dampness,qi stagnation,blood stasis,and qi deficiency,and 6 disease location syndromes,namely liver,spleen,kidney,gallbladder,stomach,and heart.The results of complex network analysis show that the core pathological syndrome of GAD is kidney,and the core pathological syndrome is yin deficiency.The joint analysis of pathological syndrome and pathological syndrome network suggests that yin deficiency is the core of the integrated network.The relationship between yin deficiency syndrome and various organs is in the order of kidney,spleen,gallbladder,liver,heart,and stomach.The syndrome element of yin deficiency has the highest correlation with being easily frightened,excessive thinking,indecisiveness,repetitive behavior,and groundless worry.The kidney syndrome has the highest correlation with the symptoms such as being easily scared,unfounded worry,repetitive actions,excessive rumination,and restlessness.Conclusion The core pathological pattern of GAD is kidney and the core pathological pattern is yin deficiency.Kidney yin deficiency may be the core pathogenesis of GAD.

Objective To evaluate the efficacy and safety of Qingre Jiedu recipe in the treatment of bipolar depression.Methods A randomized,double-blind,Chinese medicine and western medicine placebo control design was used in this study.Totally 80 subjects with bipolar depression and fiery internal depression that met the enrollment criteria,were divided into the experimental group(EG,40 cases of western medicine simulation tablets+Chinese medicine formula granules)and the control group(CG,40 cases of western medicine+Chinese medicine placebo)according to a 1∶1 ratio at last,7 cases dropped out after enrollment,EG 36 cases,CG 37 cases.TCM Heat Internal Depression Syndrome(TCMHIDS),Hamilton Depression Scale-24 Item(HAMD-24),Hamilton Anxiety Scale(HAMA),Hypomania Checklist-33(HCL-33),Young Manic Rating Scale(YMRS)and Treatment Emergent Symptom Scale(TESS)scores were assessed at baseline and at the 2nd,4th and 8th week after treatment.Important signs and adverse events were recorded.Blood routine,hepatic and renal function,urine routine and electrocardiogram were performed during the screening period and the 8th week after treatment.For the patients who dropped out of the examination program,the examination item are identical to those at week 8.The primary outcome measure was the change in HAMD score from baseline to 8th week.Secondary outcome evaluation indicators included the changes of TCMHIDS,HAMA,HCL-33 and YMRS scores from baseline to 8th week.Results The scores of the HAMD-24 between EG and CG decreased significantly compared with the baseline at different time-point,and the difference was statistically significant(P＜0.01).However,the scores of the EG on the HAMD-24 decreased more significantly compared with the CG at the 4th and 8th week,and this difference was statistically significant(P＜0.01).The TCMHIDS and HAMD scores between two groups decreased compared with the baseline at different time-point,and this difference was statistically significant(P＜0.01).However,the TCMHIDS and HAMD scores of the EG decreased more significantly ot the 4th and 8th week,compared with the CG,and this difference was statistically significant(P＜0.01).Both YMRS and HCL-33 scores decreased more significantly between two groups at different time-point,compared with the baseline,and this differences was statistically significant,but there was no difference between two groups.Conclusion TCM Qingre Jiedu recipe could effectively relieve depression and anxiety mood of bipolar depression,with more advantages than western medicine.In addition,it showed a certain effect on hypomania or manic-related symptoms of bipolar disorder,No risk of turning to hypomania or manic,better safety and less adverse reactions were observed.

Objective:To investigate the impact of evaluating the alcohol intake on all-cause mortality in patients with metabolic-associated fatty liver disease（MAFLD）and metabolic dysfunction and alcohol-related liver disease（MetALD）.Method:The retrospective study included patients aged 20 to 74 years with hepatic steatosis diagnosed by ultrasound，with data from the Third National Health and Nutrition Examination Survey（NHANES III）between 1988 and 1994. Participants were categorized into light，moderate，and heavy drinking groups according to daily alcohol intake. Multivariable-adjusted hazard ratios（aHR）and their 95% confidence intervals（ CI）were calculated by Cox proportional risk regression modeling to assess the effect of alcohol intake on all-cause mortality. Results:A total of 2 322 patients were included in the study. Males accounted for 50.2%（1 166/2 322），with a age of 42.0（31.3，57.0）years，a median follow-up of 316.0（270.0，337.0）months，and an all-cause mortality rate of 1.48% per person-year. There were 1，763 cases in the light drinking group，333 in the moderate drinking group，and 226 in the heavy drinking group.The all-cause mortality rates for patients in the three drinking groups were 1.38%，1.67%，and 2.10% per person-year，respectively. The moderate（a HR=1.37，95% CI：1.12 to 1.67， P=0.002）and heavy（a HR=1.45，95% CI：1.17 to 1.80， P=0.001）drinking groups were independently associated with increased all-cause mortality following covariate adjustment. There was a difference in all-cause mortality for alcohol intake in non-type 2 diabetes mellitus（T2DM）patients under 60 years of age（ P<0.05），but the difference was not statistically significant between non-T2DM patients over 60 years of age and T2DM patients of all ages（ P>0.05）according to the analysis of diabetes status and age subgroups. Conclusion:Alcohol intake has a dose-dependent negative effect on patients with MAFLD and MetALD. The risk of all-cause mortality increased significantly with increasing alcohol intake.

Objective:To investigate the efficacy of fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet count ratio (APRI), liver stiffness value (LSM), and Agile 3+ score and their combined model in predicting advanced-stage liver fibrosis in patients with chronic hepatitis B (CHB) combined with metabolic-associated fatty liver disease (MAFLD).Methods:A multicenter retrospective cohort study was conducted on the BMOVE population.Nine hundred twenty CHB cases combined with MAFLD who underwent liver biopsy at seven medical centers in China from April 2006 to December 2023 were included. The patients were divided into advanced-stage liver fibrosis (159 cases) and non-advanced-stage liver fibrosis (761 cases) according to the Scheuer's scoring system.The area under the receiver operating characteristic curve (AUROC), decision curve, and calibration curve analysis were used to evaluate the efficacy of the firbrosis-4 index (FIB-4) score, NFS score, APRI index, LSM, and Agile 3+ score and their combined model in predicting advanced-stage fibrosis. The liver fibrosis grade of all patients was diagnosed by liver biopsy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each scoring model and combined model, as well as the proportion of correctly classified patients, were calculated based on different cutoff values.Results:AUROC analysis showed that Agile 3+ (0.814, 95% CI: 0.787-0.838) and LSM (0.805, 95% CI: 0.778-0.829) had similar accuracy and were superior to FIB-4 (0.721, 95% CI: 0.691-0.749), NFS (0.687, 95% CI: 0.656-0.716) and APRI ( 0.689, 95% CI: 0.658-0.718); however, HBV DNA level and HBV e antigen status had no effect on this outcome. Decision curve analysis showed that interventions based on LSM and Agile 3+ had provided higher net benefits compared with serological scores. Calibration curves showed that Agile 3+ had better predicitive accuracy than all other models. Agile 3+ had the highest PPV (0.54), minimal uncertainty interval (11.6%), and the highest proportion of correctly classified patients (76%); followed by LSM (PPV: 0.43, uncertainty interval: 15.5%, correct classification rate: 66%), and FIB-4 (PPV: 0.42, uncertainty interval: 26.1%, correct classification rate: 62.6%) in terms of identifying advanced-stage liver fibrosis. Combined model analysis demonstrated that FIB-4 combined with Agile 3+ had improved the correct classification rate and reduced the proportion of missed patients compared with FIB-4 combined with LSM. Conclusion:The Agile 3+ score is superior than LSM, FIB-4, NFS, and APRI index at identifying advanced-stage fibrosis in patients with CHB combined with MAFLD. This study supports the use of FIB-4 index combined with Agile 3+ for risk stratification in patients with CHB combined with MAFLD.

Objective To explore the abnormality of top-down and bottom-up attention patterns in patients suffering from coronary heart disease(CHD)patients with heart-qi deficiency syndrome based on the theory of"five spirits".Methods From July 2024 to December 2024,30 CHD patients with heart-qi deficiency syndrome were recruited,and 30 subjects without CHD as the control group according to the principle of matching age,sex and years of education.Two groups of subjects were tested with top-down and bottom-up spatial cueing paradigm.Results Compared with the control group,CHD patients with heart-qi deficiency syndrome had longer valid reaction time(vRT)and lower average reaction time difference value(△RT)in top-down test(P＜0.05),and longer vSRT in bottom-up test.Correlation analysis showed that heart-qi deficiency syndrome score was positively correlated with top-down test indexes invalid reaction time(ivRT)(P＜0.05),negatively correlated with △RT(P＜0.01)and valid accurany(vAC)(P＜0.05).It was positively correlated with valid long reaction time(vLRT)(P＜0.01)and invalid long reaction time(ivLRT)(P＜0.01).Generalized linear model analysis showed that non-CHD subjects had shorter vRT(P＜0.01)and larger △ RT(P＜0.05)than CHD patients for top-down test.For bottom-up tests,non-CHD subjects had shorter vSRT than CHD patients(P＜0.05).Conclusion The change of top-down and bottom-up attention patterns in CHD patients with heart-qi deficiency syndrome provides a modern neuropsychological basis for the theory of"heart stores spirits".

Objective To analyze the core syndromes of patients with generalized anxiety disorder(GAD),explore the core pathogenesis,and offer innovative perspectives and practical strategies for the traditional Chinese medicine(TCM)diagnosis and treatment of GAD.Methods The basic information of GAD patients was collected,and depression symptoms were evaluated with Hamilton Anxiety Scale to evaluate anxiety symptoms,Hamilton Depression Scale,and the TCM psychiatric and somatic symptoms were evaluated with Traditional Chinese Medicine Symptom Observation Form.Based on the data collected from the Traditional Chinese Medicine symptom observation table,the systematic clustering method was used to cluster the symptoms with a frequency greater than 10％,determine the disease type syndrome and disease location syndrome,and form a syndrome symptom relationship table.According to this table,the traditional Chinese medicine syndrome score of each patient is calculated.The complex network analysis was carried out to evaluate core syndromes and analyze the relationships between core syndromes and psychiatric symptoms and core syndromes and other syndromes.Results A total of 517 patients with GAD were included.There were 81 symptoms with a frequency of more than 10％,including 21 psychological symptoms and 60 physical symptoms.The clustering analysis led to a total of 12 syndromes,including 6 pathological syndromes,namely yin deficiency,heat,phlegm dampness,qi stagnation,blood stasis,and qi deficiency,and 6 disease location syndromes,namely liver,spleen,kidney,gallbladder,stomach,and heart.The results of complex network analysis show that the core pathological syndrome of GAD is kidney,and the core pathological syndrome is yin deficiency.The joint analysis of pathological syndrome and pathological syndrome network suggests that yin deficiency is the core of the integrated network.The relationship between yin deficiency syndrome and various organs is in the order of kidney,spleen,gallbladder,liver,heart,and stomach.The syndrome element of yin deficiency has the highest correlation with being easily frightened,excessive thinking,indecisiveness,repetitive behavior,and groundless worry.The kidney syndrome has the highest correlation with the symptoms such as being easily scared,unfounded worry,repetitive actions,excessive rumination,and restlessness.Conclusion The core pathological pattern of GAD is kidney and the core pathological pattern is yin deficiency.Kidney yin deficiency may be the core pathogenesis of GAD.

Objective To evaluate the efficacy and safety of Qingre Jiedu recipe in the treatment of bipolar depression.Methods A randomized,double-blind,Chinese medicine and western medicine placebo control design was used in this study.Totally 80 subjects with bipolar depression and fiery internal depression that met the enrollment criteria,were divided into the experimental group(EG,40 cases of western medicine simulation tablets+Chinese medicine formula granules)and the control group(CG,40 cases of western medicine+Chinese medicine placebo)according to a 1∶1 ratio at last,7 cases dropped out after enrollment,EG 36 cases,CG 37 cases.TCM Heat Internal Depression Syndrome(TCMHIDS),Hamilton Depression Scale-24 Item(HAMD-24),Hamilton Anxiety Scale(HAMA),Hypomania Checklist-33(HCL-33),Young Manic Rating Scale(YMRS)and Treatment Emergent Symptom Scale(TESS)scores were assessed at baseline and at the 2nd,4th and 8th week after treatment.Important signs and adverse events were recorded.Blood routine,hepatic and renal function,urine routine and electrocardiogram were performed during the screening period and the 8th week after treatment.For the patients who dropped out of the examination program,the examination item are identical to those at week 8.The primary outcome measure was the change in HAMD score from baseline to 8th week.Secondary outcome evaluation indicators included the changes of TCMHIDS,HAMA,HCL-33 and YMRS scores from baseline to 8th week.Results The scores of the HAMD-24 between EG and CG decreased significantly compared with the baseline at different time-point,and the difference was statistically significant(P＜0.01).However,the scores of the EG on the HAMD-24 decreased more significantly compared with the CG at the 4th and 8th week,and this difference was statistically significant(P＜0.01).The TCMHIDS and HAMD scores between two groups decreased compared with the baseline at different time-point,and this difference was statistically significant(P＜0.01).However,the TCMHIDS and HAMD scores of the EG decreased more significantly ot the 4th and 8th week,compared with the CG,and this difference was statistically significant(P＜0.01).Both YMRS and HCL-33 scores decreased more significantly between two groups at different time-point,compared with the baseline,and this differences was statistically significant,but there was no difference between two groups.Conclusion TCM Qingre Jiedu recipe could effectively relieve depression and anxiety mood of bipolar depression,with more advantages than western medicine.In addition,it showed a certain effect on hypomania or manic-related symptoms of bipolar disorder,No risk of turning to hypomania or manic,better safety and less adverse reactions were observed.

Objective:To investigate the impact of evaluating the alcohol intake on all-cause mortality in patients with metabolic-associated fatty liver disease（MAFLD）and metabolic dysfunction and alcohol-related liver disease（MetALD）.Method:The retrospective study included patients aged 20 to 74 years with hepatic steatosis diagnosed by ultrasound，with data from the Third National Health and Nutrition Examination Survey（NHANES III）between 1988 and 1994. Participants were categorized into light，moderate，and heavy drinking groups according to daily alcohol intake. Multivariable-adjusted hazard ratios（aHR）and their 95% confidence intervals（ CI）were calculated by Cox proportional risk regression modeling to assess the effect of alcohol intake on all-cause mortality. Results:A total of 2 322 patients were included in the study. Males accounted for 50.2%（1 166/2 322），with a age of 42.0（31.3，57.0）years，a median follow-up of 316.0（270.0，337.0）months，and an all-cause mortality rate of 1.48% per person-year. There were 1，763 cases in the light drinking group，333 in the moderate drinking group，and 226 in the heavy drinking group.The all-cause mortality rates for patients in the three drinking groups were 1.38%，1.67%，and 2.10% per person-year，respectively. The moderate（a HR=1.37，95% CI：1.12 to 1.67， P=0.002）and heavy（a HR=1.45，95% CI：1.17 to 1.80， P=0.001）drinking groups were independently associated with increased all-cause mortality following covariate adjustment. There was a difference in all-cause mortality for alcohol intake in non-type 2 diabetes mellitus（T2DM）patients under 60 years of age（ P<0.05），but the difference was not statistically significant between non-T2DM patients over 60 years of age and T2DM patients of all ages（ P>0.05）according to the analysis of diabetes status and age subgroups. Conclusion:Alcohol intake has a dose-dependent negative effect on patients with MAFLD and MetALD. The risk of all-cause mortality increased significantly with increasing alcohol intake.