OBJECTIVE: This study investigated the antidepression mechanisms of Xiaoyaosan (XYS), a classic Chinese prescription, from the perspective of energy metabolism in the brain and intestinal tissues. METHODS: Chronic unpredictable mild stress model-a classic depression rat model-was established. Effects of XYS on behaviors and gastrointestinal motility of depressed rats were investigated. Effects of XYS on energetic charge (EC), adenosine triphosphate-related enzymes, and key enzymes of energy metabolism in both hippocampus and jejunum tissues of depressed rats were investigated using high-performance liquid chromatography, biochemical analysis, and real-time quantitative polymerase chain reaction, respectively. Spearman correlation analysis was conducted to construct a correlation network of "behavior-brain energy metabolism-intestinal energy metabolism" of depression. RESULTS: XYS significantly reduced the abnormal behaviors that observed in depressed rats and increased the EC and the activity of Na⁺-K⁺-adenosine triphosphatase (ATPase) and Ca²⁺-Mg²⁺-ATPase in hippocampus and jejunum tissues of depressed rats. XYS restored the key energetic pathways that had been interrupted by depression, including glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, XYS exhibited antidepressive effects in terms of regulating energy metabolism in tissues of both brain and intestine. CONCLUSION XYS significantly corrected the disturbances in EC and energy metabolism-related enzymes of both brain and intestinal tissues, alleviating both core and concomitant symptoms of depression. The current findings underscore the role of energy metabolism in the antidepressive activity of XYS, providing a fresh perspective on depression, and novel research strategies for revealing the mechanism of actions of traditional Chinese medicines on multi-site and multi-symptom diseases. Please cite this article as: Xiao MT, Wang SY, Wu XL, Zhao ZY, Wang HM, Liu HM, Qin XM, Liu XJ. Antidepressant mechanism of Xiaoyaosan: A perspective from energy metabolism of the brain and intestine. J Integr Med. 2025; 23(6):706-720.
Animals ; Energy Metabolism/drug effects* ; Antidepressive Agents/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Brain/drug effects* ; Male ; Depression/metabolism* ; Rats ; Rats, Sprague-Dawley ; Intestines/drug effects* ; Hippocampus/drug effects*

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

Objective:To discuss the diagnostic value of levels of growth stimulation expressed gene 2 protein(ST2),carbohydrate antigen 125(CA125),and human epididymis protein 4(HE4)in serum of the ovarian cancer patients,and to clarify their relationships with clinicopathological parameters of the ovarian cancer patients.Methods:A total of 136 patients with ovarian benign lesions or primary ovarian malignancies in our hospital confirmed by postoperative histopathology were randomly selected,including 53 cases in ovarian benign ovarian disease group and 83 cases in ovarian cancer group.Additionally,55 healthy female volunteers during the same period were enrolled as healthy control group.The fasting venous blood from all the subjects was collected on the first day of admission,and serum was retained;cyclic enhanced fluorescence immunoassay was used to detect ST2 levels of the subjects in various groups;chemiluminescence method was used to detect serum CA125 and HE4 levels of the subjects in various groups;receiver operating characteristic(ROC)curve was used to assess the diagnostic performance of each indicator;the Cut-off value and area under the ROC curve(AUC)were calculated,with AUC representing the diagnostic performance;Kendall's method was used to analyze the correlations between serum ST2 levels and TNM stage,maximum tumor diameter,distant metastasis,lymphnode metastasis,peritoneal metastasis,carcinoembryonic antigen(CEA),CA125,carbohydrate antigen 199(CA199),HE4,P53,and Kiel-67(Ki67)in the ovarian cancer patients.Results:Compared with healthy control group,the serum CA125 level of the patients in ovarian benign ovarian disease group was significantly increased(P<0.05).Compared with healthy control group and ovarian benign group,the serum levels of ST2,CA125,and HE4 of the patients in ovarian cancer group were significantly increased(P<0.05).The AUC values were 0.719(95%CI:0.616-0.822)for ST2,0.868(95%CI:0.794-0.942)for CA125,and 0.867(95%CI:0.793-0.942)for HE4.The combined detection of ST2+CA125+HE4 yielded an AUC of 0.894(95%CI:0.832-0.955).Significant differences were observed in serum ST2,CA125,and HE4 levels among ovarian cancer patients with different TNM stages,lymph node metastasis,distant metastasis,and peritoneal metastasis(P<0.05),while there were no significant differences in the patients with different ages or maximum tumor diameters(P>0.05).The ST2 level in serm of the ovarian cancer patients was positively correlated with TNM stage,distant metastasis,lymph node metastasis,peritoneal metastasis,CA125 level,HE4 level,and Ki67 level(P<0.05),but was not correlated with maximum tumor diameter,CEA,CA199 level,or P53 level(P>0.05).Conclusion:ST2,CA125,and HE4 are highly expressed in the serum of the ovarian cancer patients.Combined detection of serum ST2,CA125,and HE4 exhibits good sensitivity and specificity for ovarian cancer screening and improves diagnostic efficacy.ST2 is associated with advanced TNM stage and metastasis in ovarian cancer and may participate in the occurrence and progression of ovarian cancer.

Objective:To investigate the feasibility and safety of intracardiac echocardiography(ICE)combined with total three-dimensional(T3D)technique in zero-fluoroscopy individualized transseptal puncture.Methods:A total of 112 patients with atrial fibrillation who underwent radiofrequency ablation in Yongchuan Hospital Affiliated to Chongqing Medical University from April 2021 to March 2024 were enrolled,and according to the method for transseptal puncture,they were randomly divided into ICE+T3D group with 56 patients and ICE group with 56 patients.The two groups were analyzed in terms of baseline data,time to atrial reconstruc-tion,time to coronary sinus electrode placement,frequency of ICE probe adjustment during transseptal puncture,duration of transsep-tal puncture,pretreatment time before ablation,incidence rate of complications,and the duration and dosage of X-ray exposure.Results:There were no significant differences in baseline data between the two groups.Compared with the ICE group,the ICE+T3D group had a significantly lower frequency of ICE probe adjustment during transseptal puncture(1.70±0.63 vs.5.34±1.71,P<0.001)and the duration of transseptal puncture(3.66±1.09 min vs.4.90±1.92 min,P<0.001).Compared with the ICE group,the ICE+T3D group had significantly longer time to atrial reconstruction(22.44±3.13 min vs.12.34±2.12 min,P<0.001)and pretreatment time be-fore ablation(49.41±3.52 min vs.37.65±4.04 min,P<0.001).In the ICE+T3D group,43(76.8%)patients achieved zero radiation during pretreatment before ablation,and 13 patients received X-ray due to the difficulty in catheter placement;compared with the ICE group,the ICE+T3D group had a significantly shorter duration of X-ray exposure(1.68±0.72 min vs.3.14±1.95 min,P=0.010)and a significantly lower dosage of X-ray exposure(6.28±2.78 mGy vs.23.85±21.32 mGy,P=0.004).During the stage of transseptal punc-ture,all patients in the ICE+T3D group achieved zero radiation,while 45 patients(80.4%)in the ICE patients received X-ray.In terms of complications,there were no life-threatening complications such as cardiac tamponade,perforation of the aorta by mistake,and embolization in either group,while there was one case(1.8%)of vascular complications in each group.Conclusions:ICE combined with T3D after integration and improvement is a safe and reliable procedure for zero-fluoroscopy individualized transseptal puncture.

Objective To explore the mechanism of honey-processed Hedysari Radix in the regulation of intestinal immunity in rats with spleen qi deficiency,which was based on G protein-coupled receptor 41(GPR41)/GPR43-mediated mitogen-activated protein kinase(MAPK)signaling pathway.Methods The three-factor composite modeling method of eating disorder,diarrhea and fatigue was used to establish a model of spleen qi deficiency,and the rats were randomly divided into model,honey-processed Hedysari Radix,probiotics and blank groups with 15 rats per group.The honey-processed Hedysari Radix group was given by gavage 12.6 g·kg-1 aqueous extract of honey-processed Hedysari Radix.The probiotics group was given 0.625 g·kg-1 bifidobacterium triple viable solution by gavage.The blank and model groups were given the same dose of distilled water by gavage.Four groups were treated for 15 d with once a day.The expression levels of GPR41,GPR43,P38 MAPK,c-Jun N-terminal kinase(JNK)and extracellular regulatory protein kinase 1/2(ERK1/2)in colon tissues were detected by Western blotting.Results The relative expression levels of GPR41 in the blank,model,honey-processed Hedysari Radix and probiotics groups were 0.95±0.07,0.45±0.03,0.84±0.19 and 0.86±0.20;the relative expression levels of GPR43 were 1.17±0.11,0.41±0.06,0.66±0.03 and 0.57±0.01;the phosphorylated ERK1/2/ERK1/2 ratios were 0.16±0.01,0.43±0.01,0.39±0.01 and 0.36±0.02;the phosphorylated JNK/JNK ratios were 0.58±0.05,1.47±0.10,0.90±0.11 and 0.90±0.11;the phosphorylated P38 MAPK/P38 MAPK ratios were 1.77±0.33,3.19±0.03,2.01±0.17 and 2.23±0.59,respectively.Compared with the model group,the differences of above indexes were statistically significant in the honey-processed Hedysari Radix and probiotics groups(P＜0.05,P＜0.01).Conclusion The mechanism of honey-processed Hedysari Radix regulating intestinal immunity in rats with spleen qi deficiency is related to the regulation of GPR41/GPR43 mediated MAPK signaling pathway.

Objective:To analyze the clinical features and diagnostic process of ring chromosome syndrome.Methods:Clinical data of 9 children with ring chromosome syndrome who were treated at the Children′s Medical Center of Peking University First Hospital from September 2009 to May 2025, were summarized and analyzed in a case series study. The data included clinical manifestations, types of epileptic seizures, genetic testing, treatment outcomes, and follow-up results, et al.Results:Among the 9 children with ring chromosome syndrome, there were 6 girls and 3 boys, including 4 children with ring chromosome 20 syndrome, 3 children with ring chromosome 14 syndrome, and 1 child each with ring chromosome 13 and 17 syndrome. All 9 children had de novo chromosomal variations. Among them, 3 children of ring chromosome 20 syndrome were mosaic, and the remaining 6 children were non-mosaic. All 9 children exhibited diverse clinical features, especially those with ring chromosome 20 syndrome, which presented with specific manifestations. The 4 children with ring chromosome 20 syndrome all had acute epileptic seizures as the initial symptom, with onset ages of 67, 39, 17, and 96 months, and all had focal seizures. One child with ring chromosome 20 syndrome had non-convulsive status epilepticus. Development of all 4 children with ring chromosome 20 syndrome was normal before seizure onset, but 3 children showed regression after onset. No physical deformities were observed in 4 children with ring chromosome 20 syndrome, and 2 children were misdiagnosed, 3 children underwent whole exome sequencing and copy number variation analysis in their families, with no abnormalities detected. All 4 children with ring chromosome 20 syndrome were diagnosed through chromosomal karyotype analysis, the intervals between onset and diagnosis were 2, 81, 19 and 13 months, respectively. Follow-up showed that epileptic seizures were not controlled in all 4 children with ring chromosome 20 syndrome. The other 5 children were characterized by developmental delay as the initial symptom, followed by epileptic seizures between 3 and 24 months of age. Developmental regression of the other 5 children did not occur after onset, 2 of them had microcephaly, and 3 had wide-set eyes. No misdiagnoses were reported in these 5 children, and the intervals between onset and diagnosis were 7, 3, 55, 3, and 106 months, respectively. Follow-up showed that epileptic seizures were controlled in these 5 children. Conclusions:Ring chromosome 20 syndrome typically manifest with epilepsy as the initial symptom and are refractory to drug treatment, their early development is entirely normal. Ring chromosome 13, 14, and 17 syndrome are characterized by developmental delay from an early age, followed by the onset of epileptic seizures, which are easily controlled. Conventional whole exome sequencing and copy number variation analysis in families rarely detect ring chromosome abnormalities. Early chromosomal karyotype analysis is essential for the diagnosis of ring chromosome syndrome.

AIM To study the protective effect of Gynura divaricate polysaccharide on gouty nephropathy(GN)induced by dry yeast combined with adenine in rats.METHODS Sixty male SD rats were randomly divided into the normal group,the model group,the allopurinol group(42 mg/kg),and the low-dose,medium-dose and high-dose G.divaricate polysaccharide groups(140,280,560 mg/kg).All the rats except those of the normal group were induced into GN models by intragastrical dosing of yeast(5 g/kg)and adenine(100 mg/kg)and intervened with corresponding drug administration simultaneously.After 35 days,the rats had their levels of creatinine(Cr)and uric acid(UA)in serum and urine detected and their fraction excretion of uric acid(FEUA)value determined;their kidney mass and volume measured and their levels of kidney index and density calculated;their renal pathological changes checked by HE staining;their renal GLUT9,URAT1,ABCG2 and OAT1 mRNA expressions dectected by RT-qPCR;and their renal GLUT9,URAT1,ABCG2 and OAT1 protein expressions dectected by Western blot.RESULTS Compared with the model group,each dose of G.divaricate polysaccharide group displayed decreased levels of kidney mass,kidney volume and kidney index(P＜0.01);increased levels of kidney density(P＜0.05,P＜0.01);decreased serum levels of UA and Cr(P＜0.01);increased urine levels of UA and Cr(P＜0.01);increased FEUA value(P＜0.01);decreased GLUT9,URAT1 mRNA and protein expressions(P＜0.05,P＜0.01);and increased ABCG2,OAT1 mRNA and protein expressions(P＜0.05,P＜0.01);and more alleviated renal histological aberrations.CONCLUSION G.divaricate polysaccharide exerts good protective effects against yeast/adenine-induced GN in rats probably through down-regulating protein expression of GLUT9,URAT1 and up-regulating ABCG2 and OAT1.

AIM To evaluate the quality consistency of Tongmai Granules,Tongmai Tablets,Tongmai Capsules and Tongmai Oral Liquid.METHODS The HPLC fingerprints were established,after which the contents of danshensu,protocatechuic aldehyde,3'-hydroxy puerarin,puerarin,puerarin apioside,daidzin,ferulic acid,salvianolic acid B and salvianolic acid A were determined,and cluster analysis and principal component analysis were adopted in the quality analysis from the perspective of daily intake.RESULTS There were 21 common peaks in the fingerprints for 39 batches of samples with the similarities of 0.765-0.997.Various batches of samples were clustered into 5 categories,2 principal components demonstrated the accumulative variance contribution rate of 83.53％ .The daily intakes of various constituents in different dosage forms exhibited obvious differences,especially for that of salvianolic acid B,which were low in tablets and capsules,and their heterogeneities existed among the same dosage forms.CONCLUSION This simple and accurate method can provide a reference for the quality evaluation of Tongmai preparations from different manufacturers.

Aim To study the protective effect of the silibinin derivative Sil-1 on acute myocardial ischemia in SD rats and its mechanism of action.Methods Af-ter 18 hours of oxygen-glucose deprivation and treat-ment of H9c2 cells,the protective effect of Sil-1 on rat cardiomyocytes was examined.SD rats were treated 30 minutes before surgery,followed by 24 h ligation of the left anterior descending coronary artery.The cardiopro-tective effects of Sil-1 and its mechanisms for improving myocardial ischemic injury were investigated using pro-teomics technology.Results In vitro,compared with the control group,the activity of H9c2 cells in the mod-el group showed reduced cell viability,increased dead cells,elevated ROS and higher levels of LDH and in-flammatory cytokines TNF-α,IL-1β and IL-6 in the culture medium.Sil-1 could improve the above condi-tions to different degrees.In vivo,compared with the control group,rats in the model group showed signifi-cantly higher T waves on electrocardiogram,significant ischemic areas in the heart section,disorganized ar-rangement of cardiomyocytes,increased inflammatory factor infiltration and elevated CK,CK-MB,LDH and inflammatory factors TNF-α,IL-6 and IL-1β.Besides,NF-κB phosphorylation levels in myocardial tissue in-creased.Sil-1 improved the above conditions to varying degrees.The results of proteomics showed that 90 pro-teins were found between the control vs model group and the Sil-1 vs model group,and KEGG enrichment a-nalysis showed that MAPK,chemokines,VEGF and other signaling pathways were abundant.Western blot results showed that Sil-1 blocked the phosphorylation of ERK,JNK and p38 MAPK.Conclusions Sil-1 inhib-its the MAPK pathway by blocking the phosphorylation of JNK,ERK,and p38 MAPK,and achieves a protec-tive effect on rats with acute myocardial infarction.