Objective To investigate their potential differences in brain functional characteristics from a neuroimaging perspective,functional magnetic resonance imaging(fMRI)was employed.Methods Twenty chronic fatigue syndrome(CFS)patients were recruited and underwent assessments of traditional Chinese medicine(TCM)syndrome patterns,fatigue severity scores,and resting-state fMRI scans.First,correlation analysis was performed between fatigue scores and TCM symptom scores.Symptom clusters significantly associated with fatigue were categorized into spleen deficiency and liver stagnation groups.Principal component analysis(PCA)was then applied to identify the dominant symptom components for each group.These components were subsequently mapped onto whole-brain functional activity to compare the neural signatures between the two syndromes.Finally,the brain functional profiles of spleen deficiency and liver stagnation were compared with publicly available neurotransmitter receptor maps to explore their distinct neurochemical substrates.Results Symptoms correlated with fatigue severity included exhaustion,dizziness,chest tightness,bitter taste in the mouth,epigastric fullness,poor appetite,irritability,lumbar soreness,sallow complexion,dry eyes,and five-center-heat.The brain mapping results revealed that spleen deficiency-related symptoms(poor appetite,sallow complexion,reduced food intake,dizziness)were primarily associated with the left thalamus and left parahippocampal gyrus.Liver stagnation-related symptoms(dry eyes,chest tightness,irritability,bitter taste)were linked to the left parahippocampal gyrus and right middle occipital gyrus(lingual region).The functional brain spectrum of the two syndromes showed significant negative correlations.Moreover,the spleen deficiency spectrum was closely associated with vesicular acetylcholine transporter(VAChT)receptor density.The liver stagnation spectrum correlated with D2 dopamine receptor density.Both spectrums were significantly related to glucose metabolic density but exhibited opposing directional trends.Conclusion CFS patients with spleen deficiency and liver stagnation demonstrate distinct central functional activities and neurochemical substrates,along with opposing brain activity patterns.Clinically,differentiating between these two syndrome patterns is critical for applying targeted TCM interventions.

Objective To investigate their potential differences in brain functional characteristics from a neuroimaging perspective,functional magnetic resonance imaging(fMRI)was employed.Methods Twenty chronic fatigue syndrome(CFS)patients were recruited and underwent assessments of traditional Chinese medicine(TCM)syndrome patterns,fatigue severity scores,and resting-state fMRI scans.First,correlation analysis was performed between fatigue scores and TCM symptom scores.Symptom clusters significantly associated with fatigue were categorized into spleen deficiency and liver stagnation groups.Principal component analysis(PCA)was then applied to identify the dominant symptom components for each group.These components were subsequently mapped onto whole-brain functional activity to compare the neural signatures between the two syndromes.Finally,the brain functional profiles of spleen deficiency and liver stagnation were compared with publicly available neurotransmitter receptor maps to explore their distinct neurochemical substrates.Results Symptoms correlated with fatigue severity included exhaustion,dizziness,chest tightness,bitter taste in the mouth,epigastric fullness,poor appetite,irritability,lumbar soreness,sallow complexion,dry eyes,and five-center-heat.The brain mapping results revealed that spleen deficiency-related symptoms(poor appetite,sallow complexion,reduced food intake,dizziness)were primarily associated with the left thalamus and left parahippocampal gyrus.Liver stagnation-related symptoms(dry eyes,chest tightness,irritability,bitter taste)were linked to the left parahippocampal gyrus and right middle occipital gyrus(lingual region).The functional brain spectrum of the two syndromes showed significant negative correlations.Moreover,the spleen deficiency spectrum was closely associated with vesicular acetylcholine transporter(VAChT)receptor density.The liver stagnation spectrum correlated with D2 dopamine receptor density.Both spectrums were significantly related to glucose metabolic density but exhibited opposing directional trends.Conclusion CFS patients with spleen deficiency and liver stagnation demonstrate distinct central functional activities and neurochemical substrates,along with opposing brain activity patterns.Clinically,differentiating between these two syndrome patterns is critical for applying targeted TCM interventions.

Objective To explore the characteristics and molecular mechanisms of dynamic changes in ovarian function during natural aging in mice.Methods Eighteen female ICR mice of 2,6,10 and 14 months of age(referred to as 2 M,6 M,10 M,and 14 M)were included.The estrous cycle,ovarian index,pregnancy rate and embryo number were detected.The number of follicles was observed using HE staining.Serum anti-Müllerian hormone(AMH)levels were measured using ELISA.Protein and mRNA expression of P16,P21,proliferator-activated receptor-γ coactivator-1α(PGC-1α),and mitochondrial transcription factor A(TFAM)were detected through IHC and qPCR,respectively,and the protein expression of PGC-1α and TFAM was detected by Western blot.Relationships between indicators were evaluated based on Spearman's rank correlation coefficients and logistic regression analyses.Results Compared with estimates in the 2 M group,the percentage of estrous cycle disorders(P＜0.05 in 10 M group,P＜0.01 in 14 M group),ovarian index(P＜0.05 in 10 M group,P＜0.01 in 14 M group),serum AMH level(P＜0.01 in 10 M group,P＜0.01 in 14 M group),number of embryos(P＜0.01 in the 10 M group,P＜0.01 in 14 M group),and pregnancy rate(P＜0.01 in 14 M group)were significantly lower;the number of follicles at all levels and total number of follicles were lower(all P＜0.01),and the number of atretic follicles(all P＜0.01)was higher.Furthermore,P16 and P21 mRNA(P16:P＜0.01 in 10 M and 14 M groups;P21:P＜0.05 in 10 M group,P＜0.01 in 14 M group)and protein levels(P16:P＜0.01 in each group;P21:P＜0.01 in 10 M and 14 M groups)were elevated.Spearman's correlation analyses showed that the age in months was negatively correlated with the ovarian index,serum AMH level,primordial follicle number,number of embryos,and expression of PGC-1αand TFAM and positively correlated with the expression of atretic follicle,P16 and P21(all P＜0.01).Logistic regression analysis revealed a significant negative correlation between the age in months and pregnancy rate(P＜0.01).PGC-1α mRNA was significantly decreased(all P＜0.01),and TFAM mRNA was significantly decreased in 10 M and 14 M groups(P＜0.01).PGC-1α levels were significantly decreased in the 10 M group(IHC:P＜0.05;Western blot:P＜0.01)and 14 M group(all P＜0.01);TFAM levels were significantly lower in 6 M,10 M,and 14 M groups than in the 2 M group(IHC:P＜0.01;Western blot:P＜0.01).Compared with the 2 M group,expression levels of PGC-1α and TFAM were positively correlated with the ovarian index and serum AMH level and negatively correlated with P16 and P21 expression(all P＜0.01).Conclusions Ovarian function in mice declines progressively with age in months,as reflected by reductions in follicles and fertility and the up-regulation of aging markers,which may be associated with the decreased expression of the mitochondrial biogenesis factors PGC-1α and TFAM.

Objective To explore the characteristics and molecular mechanisms of dynamic changes in ovarian function during natural aging in mice.Methods Eighteen female ICR mice of 2,6,10 and 14 months of age(referred to as 2 M,6 M,10 M,and 14 M)were included.The estrous cycle,ovarian index,pregnancy rate and embryo number were detected.The number of follicles was observed using HE staining.Serum anti-Müllerian hormone(AMH)levels were measured using ELISA.Protein and mRNA expression of P16,P21,proliferator-activated receptor-γ coactivator-1α(PGC-1α),and mitochondrial transcription factor A(TFAM)were detected through IHC and qPCR,respectively,and the protein expression of PGC-1α and TFAM was detected by Western blot.Relationships between indicators were evaluated based on Spearman's rank correlation coefficients and logistic regression analyses.Results Compared with estimates in the 2 M group,the percentage of estrous cycle disorders(P＜0.05 in 10 M group,P＜0.01 in 14 M group),ovarian index(P＜0.05 in 10 M group,P＜0.01 in 14 M group),serum AMH level(P＜0.01 in 10 M group,P＜0.01 in 14 M group),number of embryos(P＜0.01 in the 10 M group,P＜0.01 in 14 M group),and pregnancy rate(P＜0.01 in 14 M group)were significantly lower;the number of follicles at all levels and total number of follicles were lower(all P＜0.01),and the number of atretic follicles(all P＜0.01)was higher.Furthermore,P16 and P21 mRNA(P16:P＜0.01 in 10 M and 14 M groups;P21:P＜0.05 in 10 M group,P＜0.01 in 14 M group)and protein levels(P16:P＜0.01 in each group;P21:P＜0.01 in 10 M and 14 M groups)were elevated.Spearman's correlation analyses showed that the age in months was negatively correlated with the ovarian index,serum AMH level,primordial follicle number,number of embryos,and expression of PGC-1αand TFAM and positively correlated with the expression of atretic follicle,P16 and P21(all P＜0.01).Logistic regression analysis revealed a significant negative correlation between the age in months and pregnancy rate(P＜0.01).PGC-1α mRNA was significantly decreased(all P＜0.01),and TFAM mRNA was significantly decreased in 10 M and 14 M groups(P＜0.01).PGC-1α levels were significantly decreased in the 10 M group(IHC:P＜0.05;Western blot:P＜0.01)and 14 M group(all P＜0.01);TFAM levels were significantly lower in 6 M,10 M,and 14 M groups than in the 2 M group(IHC:P＜0.01;Western blot:P＜0.01).Compared with the 2 M group,expression levels of PGC-1α and TFAM were positively correlated with the ovarian index and serum AMH level and negatively correlated with P16 and P21 expression(all P＜0.01).Conclusions Ovarian function in mice declines progressively with age in months,as reflected by reductions in follicles and fertility and the up-regulation of aging markers,which may be associated with the decreased expression of the mitochondrial biogenesis factors PGC-1α and TFAM.

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 explore the distribution patterns of traditional Chinese medicine(TCM)syndromes in patients with metabolic syndrome caused by antipsychotic drugs.Methods A standardized TCM syndrome survey was performed to collect diagnostic information from 160 patients diagnosed with metabolic syndrome due to antipsychotic drug use.Subsequent frequency analysis,cluster analysis,and Bayesian network analysis were carried out.The syndrome pattern distribution was ultimately determined through relevant literatures and expert opinions.Results Five TCM syndromes were identified through frequency,cluster,and Bayesian network analyses.The most common syndrome was qi deficiency with phlegm-dampness(30％),followed by spleen deficiency with phlegm-Heat(23.75％),qi and yin deficiency Pattern(21.88％),yin deficiency with damp-heat(17.50％),and stomach fire hyperactivity pattern(6.88％).Conclusion The pathogenesis of antipsychotics-induced metabolic syndrome involves a complex interplay of deficiency and excess factors.The primary disease is mainly located at the spleen and stomach,with involvement of the liver,kidney,and heart.Pathogenic factors include qi deficiency,yin deficiency,dampness,heat,pathogenic fire,and phlegm.

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 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 explore the distribution patterns of traditional Chinese medicine(TCM)syndromes in patients with metabolic syndrome caused by antipsychotic drugs.Methods A standardized TCM syndrome survey was performed to collect diagnostic information from 160 patients diagnosed with metabolic syndrome due to antipsychotic drug use.Subsequent frequency analysis,cluster analysis,and Bayesian network analysis were carried out.The syndrome pattern distribution was ultimately determined through relevant literatures and expert opinions.Results Five TCM syndromes were identified through frequency,cluster,and Bayesian network analyses.The most common syndrome was qi deficiency with phlegm-dampness(30％),followed by spleen deficiency with phlegm-Heat(23.75％),qi and yin deficiency Pattern(21.88％),yin deficiency with damp-heat(17.50％),and stomach fire hyperactivity pattern(6.88％).Conclusion The pathogenesis of antipsychotics-induced metabolic syndrome involves a complex interplay of deficiency and excess factors.The primary disease is mainly located at the spleen and stomach,with involvement of the liver,kidney,and heart.Pathogenic factors include qi deficiency,yin deficiency,dampness,heat,pathogenic fire,and phlegm.

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.