ObjectiveTo investigate the effect of Yuejuwan on lipid metabolism in serum， prefrontal cortex and hippocampus of depressed mice based on lipidomics， and to explore the potential pathways for improving lipid metabolism to prevent depression. MethodsSeven-week-old C57BL/6 mice were randomly divided into blank group， model group， Yuejuwan group（3.6 g·kg^-1） and fluoxetine group（10 mg·kg^-1）， and chronic unpredictable mild stress（CUMS） was used to establish the depression model. After 3 weeks of modeling， each administration group was gavaged with the corresponding drug solution according to the dose， and mice in the blank and model groups were given an equal volume of deionised water by gavage， one time/d for 2 weeks. After administration， the antidepressant effect of Yuejuwan was evaluated by neurobehavioral indices such as sucrose preference test， open field test， tail suspension test and forced swimming test. An automatic biochemical analyzer was used to measure contents of total cholesterol（TC）， triglyceride（TG）， low-density lipoprotein cholesterol（LDL-C）， high-density lipoprotein cholesterol（HDL-C）， aspartate aminotransferase（AST） and alanine aminotransferase（ALT） in mouse serum. Lipidomic analysis of mouse serum， prefrontal cortex and hippocampus was performed based on ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap mass spectrometry（UPLC-LTQ-Orbitrap-MS）， and the expression of mammalian target of rapamycin（mTOR）， ribosomal protein S6 kinase（S6K）， phosphorylation（p）-mTOR， p-S6K in gastric tissues of mice was detected by Western blot. ResultsCompared with the blank group， mice in the model group exhibited significantly reduced sucrose preference rate and center movement time in the open field test（P<0.01）， the immobility times in the tail suspension test and forced swimming test were significantly increased（P<0.01）， and serum levels of TC， TG， LDL-C， HDL-C， AST and ALT were significantly elevated（P<0.05， P<0.01）. Compared with the model group， the Yuejuwan group showed a significant increase in the sucrose preference rate and center movement time in the open field test（P<0.01）， the immobility times in the tail suspension test and forced swimming test were significantly reduced（P<0.01）， and the serum levels of TC， TG， LDL-C， AST and ALT were significantly decreased（P<0.05， P<0.01）. Lipidomic analysis revealed that Yuejuwan had a significant effect on lipid metabolism in serum， prefrontal cortex and hippocampus of depressed mice， and The differential lipid metabolites were mainly enriched in the metabolic pathways of glycerophospholipid metabolism， sphingolipid signaling， and glycosylphosphatidylinositol-anchored protein biosynthesis， among which the glycerophospholipid metabolic pathway was the most significant. Western blot results showed that compared with the blank group， the relative expression levels of p-mTOR/mTOR and p-S6K/S6K in the gastric tissues of mice in the model group were significantly increased（P<0.01）. In comparison with the model group， the relative expression levels of p-mTOR/mTOR and p-S6K/S6K in the gastric tissues of mice in the Yuejuwan group were significantly decreased（P<0.01）. ConclusionThe intervention of Yuejuwan on lipid metabolism is one of the potential pathways for its antidepressant effect， which may be related to the regulation of mTOR/S6K signaling pathway upstream of lipid metabolism in the gastric tissues.

OBJECTIVE This study investigated the clinical implications of endothelial cell-specific molecule 1(ESM-1)in obstructive sleep apnea(OSA)patients,with particular focus on its dynamic correlation with adhesion molecules,aiming to elucidate the regulatory role of ESM-1 in OSA-associated vascular endothelial impairment.METHODS This cross-sectional study enrolled participants undergoing polysomnography(PSG)at the Sleep Medicine Center of Beijing Anzhen Hospital,Capital Medical University between March 2017 and January 2018.Based on the inclusion criteria,161 participants were ultimately included and divided into OSA group(n=118)and control group(n=43).Demographic data and polysomnography parameters were collected.We used a powerful high-throughput Multiplex Immunobead Assay technology to simultaneously test plasm cytokines levels of ESM-1,inter-cellular adhesion molecule 1(ICAM-1),vascular cell adhesion molecule 1(VCAM-1).Circulating C-reactive protein(CRP)and homocysteine(Hcy)were detected by routine blood chemistry panel.RESULTS Circulating ESM-1 levels were significantly elevated in patients with OSA compared with healthy controls[819.73(612.36-1393.47)pg/ml]vs.[286.17(114.48-513.81)pg/ml,P<0.001].After adjusting for confounding factors,we found that circulating ESM-1 levels were an independent risk factor for OSA(odds ratio=2.162,95%CI=1.522-3.072,P<0.001)and circulating ESM-1 levels were positively associated with ICAM-1 and VCAM-1 levels(β=1.977,95%CI=1.429-2.734,P<0.001).CONCLUSION Circulating ESM-1 levels were significantly increased in patients with OSA,which is closely related with adhesion molecules levels.ESM-1 may be a surrogate endothelial dysfunction marker and an independent risk factor for OSA.

Objective:To construct and validate a prognostic model of colon cancer based on differentially expressed anoikis-related genes, and to preliminarily investigate the relationship between anoikis-related genes and the tumor immune microenvironment of colon cancer.Methods:A total of 472 cancer tissues samples of patients with colon cancer, RNA sequencing data and clinical data of 41 normal tissues samples were downloaded from the Cancer Genome Atlas (TCGA) database between the establishment time and July in 2024. A total of 919 genes related to anoikis were screened out from GeneCards database, and the common genes were selected from the RNA sequencing gene datasets of colon cancer and normal colon tissues in the TCGA database, among which the differentially expressed anoikis-related genes of colon cancer and normal colon tissues were screened out based on P < 0.05. Furthermore, genes related to the prognosis of 446 colon cancer patients with prognostic data in the TCGA database were screened by using univariate Cox proportional risk model; the genes with P < 0.05 were further screened out and a colon cancer prognosis model was constructed by using LASSO-Cox proportional risk model. The risk score of the above 446 colon cancer patients in the TCGA database was calculated according to the prognostic model, and the patients were divided into high-risk (≥ median value) group and low-risk (< median value) group according to the median risk score, and the overall survival of the 2 groups was analyzed by using the Kaplan-Meier method. The risk score based on R software-based time ROC program package was used to predict 1-year, 2-year, 3-year overall survival therapeutic efficacy of colon cancer patients in the TCGA database. According to the median risk score of colon cancer patients in the TCGA database, the patients in the International Cancer Genome Consortium (ICGC) database were divided into high-risk group and low-risk group. Kaplan-Meier method and receiver operating characteristic (ROC) curve were used to verify the predictive effect of the prognostic model. The differentially expressed genes between low-risk group and high-risk group stratified by prognostic model risk score in the TCGA database were used to perform single sample gene set enrichment analysis (ssGESA) of immune cells and immune function by using R software related programs. The differences in risk scores of patients with different immunophenotypes (including inflammator response type, wound healing type, interferon gamma dominant type and lymphocyte depletion type) were compared; and correlation analysis of infiltration and risk scores between immune cells and stromal cells in tumor microenvironment was made. Based on the tumor immune function and rejection (TIDE) database, the relationship between the prognostic model risk score and programmed death receptor ligand 1 (PD-L1) gene expression level was analyzed. Results:Based on anoikis-related genes in the GeneCards database, 236 differentially expressed anoikis-related genes between colon cancer tissues and normal tissues were obtained from the TCGA database. LASSO Cox regression was applied to establish a prognostic model constructed by 7 differentially expressed anoikis-related genes in cancer tissues and normal colon tissues related to the prognosis of colon cancer. Risk score = 0.366×TIMP1-0.404×NAT1+0.207×LTB4R2+0.075×INHBB+0.140×CD36-0.109×MMP3+2.994×OFCC1. The median risk score of 446 colon cancer patients in the TCGA database was 1.754 719 545. Survival analysis showed that the overall survival of colon cancer patients in high-risk group of the TCGA database was worse than that in low-risk group ( P < 0.001); ROC curve analysis showed that the area under the curve for predicting 1-year, 2-year and 3-year overall survival of patients in the TCGA database based on the prognostic model risk score was 0.705, 0.731 and 0.723, respectively. Kaplan-Meier method analysis showed that in the ICGC database, the overall survival of colon cancer patients in high-risk group was worse than that in low-risk group ( P = 0.041); ROC curve analysis showed that the area under the curve of prognostic model risk score for predicting 1-year and 2-year overall survival of colon cancer patients in the ICGC database was 0.663 and 0.966, respectively. ssGESA analysis showed that macrophage level in high-risk group was higher than that in low-risk group, helper T (Th) 1 cell and Th2 cell levels in high-risk group were lower than those in low-risk group (all P < 0.01). In terms of immune function, the cell killing activity and histocompatibility complex Ⅰ level in high-risk group were lower than those in low-risk group, and type Ⅱ interferon response score in high-risk group was higher than that in low-risk group (all P < 0.05). The analysis of immunophenotype showed that the risk score of inflammatory response type was higher than that of wound healing type ( P < 0.05), and there was no statistically significant difference in risk score between the other 2 types (all P > 0.05). Risk score was positively correlated with stromal cell infiltration score ( R = 0.340, P < 0.001) and immune cell infiltration score ( R = 0.148, P < 0.05); the expression level of PD-L1 in high-risk group was higher than that in low-risk group in the TCGA database ( P = 0.048), and the expression level of PD-L1 was positively correlated with risk score ( R = 0.130, P = 0.009). Conclusions:A prognostic model of colon cancer constructed by anoikis-related genes can better predict the prognosis of colon cancer patients, and anoikis-related genes may play an important role in tumor immunity of colon cancer.

Objective To explore changes of blood cell counts and hepatic and splenic fibrosis rates in rat models of liver cirrhosis and portal hypertension after partial splenic artery embolization(PSE).Methods Fifteen rat models of liver cirrhosis and portal hypertension were successfully established.Red blood cell(RBC),white blood cell(WBC)and platelet(PLT)counts were measured.Splenic artery angiography and PSE were performed in 10 rats(PSE group),while only splenic artery angiography was performed in the rest 5 rats(control group).1 week after interventions,RBC,WBC and PLT counts were remeasured,and then the rats were euthanized to obtain liver and spleen specimens for pathological examination and evaluation of fibrosis rate.The changes of blood cell count within 1 week and the hepatic and splenic fibrosis rates 1 week after intervention were compared between groups.Results Rats in both groups exhibited good general condition within 1 week after intervention.One week after intervention,RBC,WBC and PLT counts in PSE group were all significantly higher than those before intervention(all P＜0.05),and the increasing rate of RBC,WBC and PLT counts in PSE group were larger than those in control group(all P＜0.05).WBC and PLT counts in PSE group 1 week after intervention were all higher than those in control group(both P＜0.05),but no significant difference of RBC count was observed between groups(P＞0.05).One week after intervention,hepatic fibrosis rate was higher,while splenic fibrosis rate was lower in PSE group than that in control group(both P＜0.05).Conclusion PSE might be used to improve decrease of blood cell count caused by hypersplenism in rat with liver cirrhosis and portal hypertension,hence reverse or slow down progression of splenic fibrosis.

Objective To explore changes of blood cell counts and hepatic and splenic fibrosis rates in rat models of liver cirrhosis and portal hypertension after partial splenic artery embolization(PSE).Methods Fifteen rat models of liver cirrhosis and portal hypertension were successfully established.Red blood cell(RBC),white blood cell(WBC)and platelet(PLT)counts were measured.Splenic artery angiography and PSE were performed in 10 rats(PSE group),while only splenic artery angiography was performed in the rest 5 rats(control group).1 week after interventions,RBC,WBC and PLT counts were remeasured,and then the rats were euthanized to obtain liver and spleen specimens for pathological examination and evaluation of fibrosis rate.The changes of blood cell count within 1 week and the hepatic and splenic fibrosis rates 1 week after intervention were compared between groups.Results Rats in both groups exhibited good general condition within 1 week after intervention.One week after intervention,RBC,WBC and PLT counts in PSE group were all significantly higher than those before intervention(all P＜0.05),and the increasing rate of RBC,WBC and PLT counts in PSE group were larger than those in control group(all P＜0.05).WBC and PLT counts in PSE group 1 week after intervention were all higher than those in control group(both P＜0.05),but no significant difference of RBC count was observed between groups(P＞0.05).One week after intervention,hepatic fibrosis rate was higher,while splenic fibrosis rate was lower in PSE group than that in control group(both P＜0.05).Conclusion PSE might be used to improve decrease of blood cell count caused by hypersplenism in rat with liver cirrhosis and portal hypertension,hence reverse or slow down progression of splenic fibrosis.

Objective:To construct and validate a prognostic model of colon cancer based on differentially expressed anoikis-related genes, and to preliminarily investigate the relationship between anoikis-related genes and the tumor immune microenvironment of colon cancer.Methods:A total of 472 cancer tissues samples of patients with colon cancer, RNA sequencing data and clinical data of 41 normal tissues samples were downloaded from the Cancer Genome Atlas (TCGA) database between the establishment time and July in 2024. A total of 919 genes related to anoikis were screened out from GeneCards database, and the common genes were selected from the RNA sequencing gene datasets of colon cancer and normal colon tissues in the TCGA database, among which the differentially expressed anoikis-related genes of colon cancer and normal colon tissues were screened out based on P < 0.05. Furthermore, genes related to the prognosis of 446 colon cancer patients with prognostic data in the TCGA database were screened by using univariate Cox proportional risk model; the genes with P < 0.05 were further screened out and a colon cancer prognosis model was constructed by using LASSO-Cox proportional risk model. The risk score of the above 446 colon cancer patients in the TCGA database was calculated according to the prognostic model, and the patients were divided into high-risk (≥ median value) group and low-risk (< median value) group according to the median risk score, and the overall survival of the 2 groups was analyzed by using the Kaplan-Meier method. The risk score based on R software-based time ROC program package was used to predict 1-year, 2-year, 3-year overall survival therapeutic efficacy of colon cancer patients in the TCGA database. According to the median risk score of colon cancer patients in the TCGA database, the patients in the International Cancer Genome Consortium (ICGC) database were divided into high-risk group and low-risk group. Kaplan-Meier method and receiver operating characteristic (ROC) curve were used to verify the predictive effect of the prognostic model. The differentially expressed genes between low-risk group and high-risk group stratified by prognostic model risk score in the TCGA database were used to perform single sample gene set enrichment analysis (ssGESA) of immune cells and immune function by using R software related programs. The differences in risk scores of patients with different immunophenotypes (including inflammator response type, wound healing type, interferon gamma dominant type and lymphocyte depletion type) were compared; and correlation analysis of infiltration and risk scores between immune cells and stromal cells in tumor microenvironment was made. Based on the tumor immune function and rejection (TIDE) database, the relationship between the prognostic model risk score and programmed death receptor ligand 1 (PD-L1) gene expression level was analyzed. Results:Based on anoikis-related genes in the GeneCards database, 236 differentially expressed anoikis-related genes between colon cancer tissues and normal tissues were obtained from the TCGA database. LASSO Cox regression was applied to establish a prognostic model constructed by 7 differentially expressed anoikis-related genes in cancer tissues and normal colon tissues related to the prognosis of colon cancer. Risk score = 0.366×TIMP1-0.404×NAT1+0.207×LTB4R2+0.075×INHBB+0.140×CD36-0.109×MMP3+2.994×OFCC1. The median risk score of 446 colon cancer patients in the TCGA database was 1.754 719 545. Survival analysis showed that the overall survival of colon cancer patients in high-risk group of the TCGA database was worse than that in low-risk group ( P < 0.001); ROC curve analysis showed that the area under the curve for predicting 1-year, 2-year and 3-year overall survival of patients in the TCGA database based on the prognostic model risk score was 0.705, 0.731 and 0.723, respectively. Kaplan-Meier method analysis showed that in the ICGC database, the overall survival of colon cancer patients in high-risk group was worse than that in low-risk group ( P = 0.041); ROC curve analysis showed that the area under the curve of prognostic model risk score for predicting 1-year and 2-year overall survival of colon cancer patients in the ICGC database was 0.663 and 0.966, respectively. ssGESA analysis showed that macrophage level in high-risk group was higher than that in low-risk group, helper T (Th) 1 cell and Th2 cell levels in high-risk group were lower than those in low-risk group (all P < 0.01). In terms of immune function, the cell killing activity and histocompatibility complex Ⅰ level in high-risk group were lower than those in low-risk group, and type Ⅱ interferon response score in high-risk group was higher than that in low-risk group (all P < 0.05). The analysis of immunophenotype showed that the risk score of inflammatory response type was higher than that of wound healing type ( P < 0.05), and there was no statistically significant difference in risk score between the other 2 types (all P > 0.05). Risk score was positively correlated with stromal cell infiltration score ( R = 0.340, P < 0.001) and immune cell infiltration score ( R = 0.148, P < 0.05); the expression level of PD-L1 in high-risk group was higher than that in low-risk group in the TCGA database ( P = 0.048), and the expression level of PD-L1 was positively correlated with risk score ( R = 0.130, P = 0.009). Conclusions:A prognostic model of colon cancer constructed by anoikis-related genes can better predict the prognosis of colon cancer patients, and anoikis-related genes may play an important role in tumor immunity of colon cancer.

Objective:To develop a recombinant protein vaccine based on KPC-2, a drug resistance target in Klebsiella pneumoniae, and evaluate its immunogenicity, protective efficacy and mechanism in a mouse model of pneumonia. Methods:KPC-2 was expressed in Escherichia coli and purified using GST affinity chromatography. A recombinant protein vaccine was prepared with KPC-2 and used to immunize New Zealand rabbits through subcutaneous injection. Serum samples were isolated from cardiac blood and Protein G chromatography was used to purify polyclonal antibodies against KPC-2. Opsonophagocytic killing assay was used to assess the bactericidal activity of the polyclonal antibodies in vitro. Female BALB/c mice were immunized three times with the recombinant protein vaccine, and the titers of specific IgG antibodies in serum were measured by indirect ELISA. One week after the last vaccination, the mice were infected with Klebsiella pneumoniae strain SRT through tracheal intubation, and received a single intravenous dose of meropenem (0.1 mg) 1 h later. The protective efficacy of the KPC-2 recombinant protein vaccine was evaluated by comparing the survival rates, bacterial colonization and histopathological changes between vaccine group and adjuvant group as well as the survival rates between meropenem group and normal saline group. Moreover, the protective efficacy of polyclonal antibodies against KPC-2 was evaluated through passive immunization. Results:The level of specific IgG antibodies in serum was significantly higher in the vaccine group than in the adjuvant group ( t=4.325, P<0.05). The survival rate in the vaccine group was also higher than that of the adjuvant group [70% (7/10) vs 10% (1/10), P<0.05]. Furthermore, lung inflammation was less severe and bacterial burden was reduced in the vaccine group as compared with those of the control group ( t=3.127, P<0.05). Both active and passive vaccination strategies demonstrated strong protective efficacy against Klebsiella pneumoniae infection, and had a synergistic effect when used in combination with antibiotic therapy. The polyclonal antibodies against KPC-2 had bactericidal activity in vitro ( t=5.427, P<0.05). Conclusions:The prepared KPC-2 vaccine has better immunogenicity and protective efficacy. It can induce strong humoral immune responses. This study suggest that drug resistance target may be used as a candidate antigen for future vaccine development.

Objective To compare and analyze the clinical characteristics and efficacy of transjugular intrahepatic portosystemic shunt(TIPS)in the treatment of liver cirrhosis with different portal vein thrombosis(PVT)grades.Methods A retrospective analysis was performed on 75 patients with liver cirrhosis and gastrointestinal bleeding who received TIPS.According to the Yerdel scale of PVT,the patients were divided into type Ⅰ(34 cases),type Ⅱ(25 cases)and type Ⅲ(16 cases).The patients were followed up 1,3,6 months after TIPS and every 6 months thereafter to compare the clinical data and the efficacy of TIPS in three types of PVT patients.Results The success rate of TIPS in three types of patients was 100％.There were differences in platelet to lymphocyte ratio(PLR)and proportion of different Child-Pugh grades among the three types of patients(P＜0.05).After TIPS,portal vein pressure was decreased compared with that before TIPS(P＜0.001).However,there were no significant differences in postoperative survival rate,rebleeding rate,over hepatic encephalopathy rate,stent dysfunction rate,thrombus complete recanalization rate and thrombus recurrence rate(P＞0.05).Conclusion The success rate of TIPS in three types of patients is higher,and the portal vein pressure is decreased significantly after TIPS,but there are no significant differences in the postoperative efficacy.Although the implementation of TIPS in cirrhotic PVT patients is challenging,it is still worth the effort to reshape the portal vein for the benefit of patients.

Objective To investigate the effect of altered oxidative stress system on liver function after partial splenic embolization(PSE).Methods Twenty-nine patients with liver cirrhosis and hypersplenism who received PSE were selected.Peripheral venous blood was drawn from the patients before and at 1 week,1 month,and 3 months after PSE,and the indexes of oxidative stress system factors including malondialdehyde(MDA),superoxide dismutase(SOD),advanced oxidiation protein products(AOPPs),and gluta-thione peroxidase(GSH-Px)were detected,as well as liver function indexes.Results There were positive correlation between SOD activity and total bilirubin(TBil)and model for end-stage liver disease(MELD)scores at 1 week postoperatively(TBil:r=0.725,P＜0.05;MELD:r=0.764,P＜0.05).There was positive correlation between GSH-Px activity and alanine aminotransferase(ALT)at 1 month postoperatively(r=0.777,P＜0.05),however,the AOPPs was negatively correlated with ALT and aspartate aminotransferase(AST)at 3 months postoperatively(ALT:r--0.900,P＜0.05;AST:r=-0.957,P＜0.05).Conclusion PSE can improve the body oxidative stress system and enhance the body's antioxidant response,and then improve the liver function.