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 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 the clinical characteristics of cirrhosis with or without portal vein thrombosis(PVT),and to analyze the therapeutic effect of transjugular intrahepatic portosystemic shunt(TIPS)in treating cirrhosis with or without PVT.Methods The clinical data of 193 patients with cirrhosis complicated by gastrointestinal bleeding,who received TIPS from October 2018 to October 2022,were retrospectively analyzed.According to the presence or absence of PVT before TIPS,the patients were divided into non-PVT group(n=118)and PVT group(n=75).After TIPS,the patients were followed up at one,3,6 months and every 6 months thereafter.The effect of PVT on the clinical characteristics of cirrhosis patients and on the therapeutic efficacy after TIPS were analyzed.Results The success rate of TIPS was 100％in both groups.The proportion of carrying out splenectomy or partial splenic artery embolization(PSE)in PVT group was 26.7％(20/75),which was obviously higher than 13.6％(16/118)in non-PVT group,the difference between the two groups was statistically significant(x2=5.192,P=0.023).In PVT group the preoperative Child-Pugh score,the model of end-stage liver disease(MELD)score and serum sodium model of end-stage liver disease(MELD-Na+)score were(8.1±1.9)points,(9.2±8.0)pointsand(9.2±8.0)points respectively,which in non-PVT group were(7.4±1.9)points,(7.7±5.8)points and(7.7±5.8)points respectively,the differences between the two groups were statistically significant(all P＜0.05).The incidence of overt hepatic encephalopathy in PVT group was 33.3％(25/75),which was strikingly higher than 19.5％(23/118)in non-PVT group,the difference between the two groups was statistically significant(P=0.030).No statistically significant differences in postoperative survival rate,rebleeding rate and stent dysfunction rate existed between the two groups(all P＞0.05).Conclusion For the treatment of cirrhotic patients with PVT complicated by gastrointestinal bleeding,TIPS is clinically safe and effective.In cirrhotic patients with PVT,the worse the liver function is,the higher the incidence of overt hepatic encephalopathy after TIPS will be.

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.

Objective To investigate the changes of serum nuclear factor κB(NF-κB),high mobility group box 1 protein(HMGB1)and heat shock protein 70(HSP70)in children with febrile seizures(FS),and to analyze their relationships with brain injury and myocardial injury.Methods Sixty FS children who were admitted to The Affiliated Hospital of Xuzhou Medical University from January 2020 to December 2021 were enrolled in this study.There were 37 children with simple febrile seizures(SFS)and 23 children with complex febrile seizures(CFS).In addition,30 febrile children without convulsion were selected as controls.The levels of NF-κB,MGB1,HSP70,serum brain-derived neurotrophic factor(BDNF),creatine kinase isoenzyme(CK-MB)and lactate dehydrogenase(LDH)were compared among the three groups.Pearson correlation analysis was used to analyze the relationships of NF-κB,MGB1 and HSP70 with BDNF,CK-MB and LDH.Results There were significant differences in BDNF,NF-κB,MGB1,HSP70,CK-MB and LDH among the three groups(all P<0.05).NF-κB was positively correlated with BDNF,CK-MB and LDH(all P<0.05).MGB1 was positively correlated with BDNF,CK-MB and LDH(all P<0.05).HSP70 was positively correlated with BDNF,CK-MB and LDH(all P<0.05).Conclusion The levels of NF-κB,MGB1 and HSP70 are significantly increased in children with FS,and were associated with brain nerve injury and myocardial injury.

Hepatic cholesterol accumulation is an important contributor to hypercholesterolemia, which results in atherosclerosis and cardiovascular disease (CVD). ATP-citrate lyase (ACLY) is a key lipogenic enzyme that converts cytosolic citrate derived from tricarboxylic acid cycle (TCA cycle) to acetyl-CoA in the cytoplasm. Therefore, ACLY represents a link between mitochondria oxidative phosphorylation and cytosolic de novo lipogenesis. In this study, we developed the small molecule 326E with an enedioic acid structural moiety as a novel ACLY inhibitor, and its CoA-conjugated form 326E-CoA inhibited ACLY activity with an IC₅₀ = 5.31 ± 1.2 μmol/L in vitro. 326E treatment reduced de novo lipogenesis, and increased cholesterol efflux in vitro and in vivo. 326E was rapidly absorbed after oral administration, exhibited a higher blood exposure than that of the approved ACLY inhibitor bempedoic acid (BA) used for hypercholesterolemia. Chronic 326E treatment in hamsters and rhesus monkeys resulted in remarkable improvement of hyperlipidemia. Once daily oral administration of 326E for 24 weeks prevented the occurrence of atherosclerosis in ApoE^-/- mice to a greater extent than that of BA treatment. Taken together, our data suggest that inhibition of ACLY by 326E represents a promising strategy for the treatment of hypercholesterolemia.

OBJECTIVE: To summarize the application experience and clinical effect of radial artery in total arterial coronary revascularization (TAR) in elderly patients. METHODS: Retrospectively analyzed the clinical data of patients who underwent TAR at the University of Hong Kong Shenzhen Hospital from July 1, 2020 to May 30, 2022. Patients were divided into ≥ 65-year-old group and < 65-year-old group according to age. The radial artery blood flow, diameter, intimal integrity and Allen test were evaluated by ultrasound before operation. The distal ends of radial artery were collected for pathological examination during operation. Coronary artery CT angiography (CTA) was examined postoperatively and follow up. The safety and reliability of ultrasonic assessment of radial artery and application of radial artery in elderly patients with TAR were summarized and analyzed. RESULTS: A total of 101 patients received TAR, including 35 cases aged ≥ 65 years old, 66 cases aged < 65 years old; 78 cases used bilateral radial arteries, and 23 cases used unilateral radial arteries. 4 cases of bilateral internal mammary arteries. All the proximal ends of the radial artery were anastomosed to the proximal end of the ascending aorta, 34 cases were performed of "Y" grafts, and 4 cases were sequential anastomoses. There was no in-hospital death and perioperative cardiovascular events. Perioperative cerebral infarction occurred in 3 patients. 1 patients was reoperated for bleeding. Intra-aortic balloon pump (IABP) assistance was used in 21 patients. Poor wound healing occurred in 2 cases and healed well after debridement. Follow-up of 2 to 20 months after discharge showed no internal mammary artery occlusion and 4 radial artery occlusions; no major adverse cardiovascular and cerebrovascular event (MACCE) occurred, and the survival rate was 100%. There was no significant difference in the above perioperative complications and follow-up endpoints between the two age groups. CONCLUSIONS By adjusting the order of bypass anastomosis and optimizing the preoperative evaluation method, radial artery combined with internal mammary artery can obtain better outcome early in TAR, and can be safely and reliably applied to elderly patients.
Aged ; Humans ; Radial Artery/transplantation* ; Coronary Vessels ; Coronary Artery Bypass/methods* ; Retrospective Studies ; Reproducibility of Results ; Treatment Outcome