OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

S-methyl-L-cysteine sulfoxide (SMCO) is a non-protein sulfur-containing amino acid with a variety of functions. There are few reports on the enzymes catalyzing the biosynthesis of SMCO from S-methyl-L-cysteine (SMC). In this study, the flavin-containing monooxygenase gene derived from Schizosaccharomyces pombe (spfmo) was heterologously expressed in Escherichia coli BL21(DE3) and the enzymatic properties of the expressed protein were analyzed. The optimum catalytic conditions of the recombinant SpFMO were 30 ℃ and pH 8.0, under which the enzyme activity reached 72.77 U/g. An appropriate amount of Mg²⁺ improved the enzyme activity. The enzyme kinetic analysis showed that the K_m and k_cat/K_m of SpFMO on the substrate SMC were 23.89 μmol/L and 61.71 L/(min·mmol), respectively. Under the optimal reaction conditions, the yield of SMCO synthesized from SMC catalyzed by SpFMO was 12.31% within 9 h. This study provides reference for the enzymatic synthesis of SMCO.
Schizosaccharomyces/genetics* ; Escherichia coli/metabolism* ; Recombinant Proteins/metabolism* ; Cysteine/biosynthesis* ; Mixed Function Oxygenases/metabolism* ; Schizosaccharomyces pombe Proteins/metabolism* ; Oxygenases/metabolism* ; Kinetics

Objective To understand the respiratory protection competency of staff in hospitals.Methods Staff from six hospitals of different levels and characteristics in Beijing were selected,including doctors,nurses,medical technicians,and servicers,to conduct knowledge assessment on respiratory protection competency.According to exposure risks of respiratory infectious diseases,based on actual cases and daily work scenarios,content of respira-tory protection competency assessment was designed from three aspects:identification of respiratory infectious di-seases,transmission routes and corresponding protection requirements,as well as correct selection and use of masks.The assessment included 6,6,and 8 knowledge points respectively,with 20 knowledge points in total,all of which were choice questions.For multiple-choice questions,full marks,partial marks,and no mark were given respective-ly if all options were correct,partial options were correct and without incorrect options,and partial options were correct but with incorrect options.Difficulty and discrimination analyses on question of each knowledge point was conducted based on classical test theory.Results The respiratory protection competency knowledge assessment for 326 staff members at different risk levels in 6 hospitals showed that concerning the 20 knowledge points,more than 60％participants got full marks for 6 points,while the proportion of full marks for other questions was relatively low.Less than 10％participants got full marks for the following 5 knowledge points:types of airborne diseases,types of droplet-borne diseases,conventional measures for the prevention and control of healthcare-associated infec-tion with respiratory infectious diseases,indications for wearing respirators,and indications for wearing medical protective masks.Among the 20 knowledge questions,5,1,and 14 questions were relatively easy,medium,and difficult,respectively;6,1,4,and 9 questions were with discrimination levels of ≥0.4,0.30-0.39,0.20-0.29,and ≤0.19,respectively.Conclusion There is still much room for hospital staff to improve their respiratory protection competency,especially in the recognition of diseases with different transmission routes and the indications for wearing different types of masks.

Objective:To investigate the changes of Notch signaling molecules and Th22 cells in adult patients with infectious mononucleosis(IM),and assess the regulatory function of Notch signaling inhibition to Th22 cells.Methods:Forty-two IM patients and twenty-one healthy controls were enrolled in this study.Their peripheral blood was collected,from which plasma and peripheral blood mononuclear cells(PBMCs)were isolated.Plasma interleukin(IL)-17 and IL-22 were measured by enzyme-linked immunosorbent assay.The percentages of CD3+CD4+IL-17+Th17 cells and CD3+CD4+IL-22+Th22 cells were investigated by flow cytometry.The mRNA relative levels corresponding to Th1 7 transcription factor retinoic acid related orphan receptor γt(RORγt),Th22 transcription factor aryl hydrocarbon receptor(AhR),and Notch signaling pathway molecules(including Notch receptors,Notch ligands,Notch downstream molecules)were semi-quantified by real-time PCR.CD4+T cells were purified and stimulated with γ-secretase inhibitor(GSI).Cellular proliferation,Th17 and Th22 percentage,IL-17 and IL-22 secretion,transcription factor mRNA were measured in response to GSI stimulation.Results:The relative expression levels of Notch1 and Notch2 mRNA in PBMCs of IM group were 13.58±3.18 and 4.73±1.16,respectively,which were significantly higher than 1.09± 0.12 and 1.07±0.15 in PBMCs of control group(both P＜0.001).However,there were no significant differences in relative expression levels of Notch3 and Notch4 mRNA between IM group and control group(P＞0.05).The relative expression levels of Notch ligands(including DLL1 and Jagged1)mRNA and Notch downstream molecules(including Hes1,Hes5,and Hey1)were increased in IM group compared with control group(all P＜0.001).In IM group,the Th17 and Th22 percentage were 5.03％±1.15％and 4.48％±1.29％,respectively,which were both higher than 4.36％±0.82％and 3.83％±0.55％in control group(both P＜0.05).In IM group,the IL-17 and IL-22 level were(301.1±53.82)and(101.2±16.45)pg/ml,respectively,which were both higher than(237.2±72.18)and(84.75 ±11.83)pg/ml in control group(both P＜0.001).In IM group,the relative expression levels of RORγt and AhR mRNA were 1.25±0.22 and 1.21±0.12,respectively,which were both higher than 0.99±0.15 and 1.04±0.11 in control group(both P＜0.001).There were no remarkable differences in CD4+T cell proliferation,Th17 percentage,IL-17 secretion,and relative expression level of RORγt mRNA between cells with GSI stimulation and without GSI stimulation(P＞0.05).GSI stimulation reduced Th22 percentage,IL-22 secretion,and relative expression level of AhR mRNA compared with non-stimulation(all P＜0.05).Conclusion:Notch signaling pathway regulates IL-22 secretion by CD4+T cells via AhR in IM patients.Notch-AhR-Th22 pathway may take part in the pathogenesis of IM.

Objectives:We aimed to compare the impact of dissection and re-entry(DR)recanalizing pattern with non-DR on the in-hospital results and prognostic outcomes of patients treated successfully by percutaneous coronary intervention(PCI)of chronic total occlusion(CTO)and examine the benefit of DR in CTO PCI. Methods:A total of 815 consecutive patients with CTO meeting the inclusion criteria in the Department of Cardiology of the First Affiliated Hospital of PLA Air Force Military Medical University from January 2018 to December 2020 were enrolled and divided into DR group(n=239)and non-DR group(n=576)according to whether DR recanalizing pattern was used in the procedure.The clinical characteristics,coronary angiographic characteristics,procedure results,and complications were collected,and the prognostic outcomes within one year after the procedure were observed.Propensity score matching by the clinical and coronary angiographic characteristics was performed and results were compared with 208 matched patients in each group.The endpoints were the major adverse cardiovascular events(MACE)consisting of all-cause death and myocardial infarction,clinically driven target vessel revascularization(TVR)one year after the procedure,and in-hospital outcomes. Results:The mean age of all patients was(60.9±10.9)years old,and 87.4%were male.As compared with the non-DR group,the proportion of blunt cap,ambiguous,calcification,angle＞45°,and diseased landing zone,as well as mean J-CTO score was higher in the DR group(all P＜0.05).The mean stent length and median procedure time were longer in the DR group,median guidewires and consumed contrast volume was also higher in the DR group(all P＜0.001).Incidence of in-hospital death,myocardial infarction,perforation,side branch loss,bleeding of BARC 3rd grade and above,and contrast-related impairment of renal function were similar between the two groups(all P＞0.05).However,peripheral vascular complications occurred more frequently in the DR group(P=0.007).One year after the procedure,the incidence of MACE(2.9%vs.2.4%,log-rank P=0.750)and clinically driven TVR(5.8%vs.3.9%,log-rank P=0.365)as well as all-cause death(2.9%vs.1.0%,log-rank P=0.154)and myocardial infarction(0.5%vs.1.9%,log-rank P=0.184)were similar between the two matched groups.Multivariate Cox regression analysis showed no significant association between DR and MACE(HR=1.129,95%CI:0.427-2.979,P=0.807)and TVR(HR=0.606,95%CI:0.213-1.722,P=0.347).LVEF≤40%(HR=2.775,95%CI:1.137-6.774,P=0.025)and elevated residual SYNTAX score(HR=1.089,95%CI:1.032-1.150,P=0.002)were risk factors for MACE,and diseased landing zone(HR=2.144,95%CI:1.019-4.513,P=0.045),rescued ADR(HR=3.479,95%CI:1.109-10.919,P=0.033),and prolonged procedure time(HR=1.007,95%CI:1.002-1.013,P=0.007)were risk factors for TVR. Conclusions:CTO lesion recanalized with PCI utilizing DR operation pattern was associated with more complex characteristics,more devices and time consumed,and longer stent length,while no significant association was observed between DR operation pattern and MACE and TVR one year after the procedure,as well as in-hospital complication..

Objective We aimed to compare the efficacy and prognosis of percutaneous coronary intervention(PCI)in complex and high-risk patients with coronary heart disease(CHD)treated with extracorporeal membrane oxygenation(ECMO)combined with intra-aortic balloon pump(IABP)assistance,and explore the application value of combined use of mechanical circulatory support(MCS)devices in complex PCI.Methods A total of patients who met the inclusion criteria and underwent selective PCI supported by MCS at the Department of Cardiology,the First Affiliated Hospital of the Air Force Medical University from January 2018 to December 2022 were continuously enrolled.According to the mechanical circulatory support method,the patients were divided into ECMO+IABP group and IABP group.Clinical characteristics,angiographic features,in-hospital outcomes,and complications were collected.The intra-hospital outcomes and major adverse cardiovascular events(MACE)at one month and one year after the procedure were observed.The differences and independent risk factors between the two groups in the above indicators were analyzed.Results A total of 218 patients undergoing elective PCI were included,of which 66 patients were in the ECMO+IABP group and 152 patients were in the IABP group.The baseline characteristics of the two groups of patients were generally comparable,but the ECMO+IABP group had more complex lesion characteristics.The proportion of patients with atrial fibrillation(6.1％vs.0.7％,P=0.030),left main disease(43.9％vs.27.0％,P=0.018),triple vessel disease(90.9％vs.75.5％,P=0.009),and RCA chronic total occlusion disease(60.6％vs.35.5％,P＜0.001)was higher in the ECMO+IABP group compared to the IABP group.The proportion of patients with previous PCI history was higher in the IABP group(32.9％vs.16.7％,P=0.014).There was no statistically significant difference in the incidence of in-hospital complications between the two groups(P=0.176),but the incidence of hypotension after PCI was higher in the ECMO+IABP group(19.7％vs.9.2％,P=0.031).The rates of 1-month MACE(4.5％vs.2.6％,P=0.435)and 1-year MACE(7.6％vs.7.9％,P=0.936)were comparable between the two groups.Multivariate analysis showed that in-hospital cardiac arrest(OR 7.17,95％CI 1.27-40.38,P=0.025)and after procedure hypotension(OR 3.60,95％CI 1.10-11.83,P=0.035)were independent risk factors for the occurrence of 1-year MACE.Conclusions Combination use of ECMO+IABP support can provide complex and high-risk coronary heart disease patients with an opportunity to achieve coronary artery revascularization through PCI,and achieve satisfactory long-term prognosis.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

Objective:To summarise and analyse the experience in the diagnosis and management of abdominal aortic endograft infection in recent years.Methods:Retrospectively summarised and analysed the general data, clinical presentation, laboratory and imaging findings, causative organisms and treatment choices of 14 patients with abdominal aortic endograft infection treated in Beijing Friendship Hospital, Capital Medical University, from January 2018 to June 2024, and analysed the prognosis of the patients and the risk factors associated with prognosis.Results:Positive bacterial cultures were 10 out of 14 patients. One non-operatively treated patient died of infectious toxic shock. Thirteen surgically treated patients underwent axillary-bifemoral artery bypass, removal of the infected stent, and closure of the aortic stump. Four of the 13 cases had combined aortoenteric fistula, 3 cases underwent one-stage enterocutaneous fistula repair, 1 case only fistula drainage, 3 cases of gastrojejunal anastomosis, all of them underwent gastric or jejunal nutrient tube implantation. Two of the 13 patients had combined the infection foci spread to the renal artery openings. To save the kidney, intraoperative left kidney autologous renal transplantation was performed in 1 case, and autologous saphenous vein reconstruction from celiac trunk artery-left renal artery and superior mesenteric artery-right renal artery was performed in the other case. All 14 patients were retrospectively summarised and followed up in August 2024, with 5 deaths in the early postoperative period (< 3 months), 3 deaths in the mid- to long-term period (≥3 months), and 5 survivors, with a median follow-up time of 2 years (1-5 years) for surviving patients. Among the 13 operated patients, 4 cases were combined with aortoenteric fistula, and 3 cases died in the early postoperative period; 4 cases of abdominal aortic infection foci involving renal artery openings, 2 cases of early postoperative death; 4 cases with pleural effusion, 4 cases died in the early postoperative period; 2 cases of combined creatinine elevation, 2 cases of early postoperative death; 2 cases of postoperative infection of artificial blood vessels.Conclusions:Abdominal aortic endograft infection are aggressive. The risk of early death is increased in patients who are elderly, in poor general condition, with aortoenteric fistula or with pre-existing cardiac, pulmonary, hepatic and renal insufficiency, but surgery based on adequate anti-infective therapy remains an effective means of saving the patient′s life.

Several mitochondrial dysfunctions in obesity and diabetes include impaired mitochondrial membrane potential, excessive mitochondrial reactive oxygen species generation, reduced mitochondrial DNA, increased mitochondrial Ca2+ flux, and mitochondrial dynamics disorders. Mitophagy, specialized autophagy, is responsible for clearing dysfunctional mitochondria in physiological and pathological conditions. As a paradox, inhibition and activation of mitophagy have been observed in obesity and diabetes-related heart disorders, with both exerting bidirectional effects. Suppressed mitophagy is beneficial to mitochondrial homeostasis, also known as benign mitophagy. On the contrary, in most cases, excessive mitophagy is harmful to dysfunctional mitochondria elimination and thus is defined as detrimental mitophagy. In obesity and diabetes, two classical pathways appear to regulate mitophagy, including PTEN-induced putative kinase 1 (PINK1)/Parkin-dependent mitophagy and receptors/adapters-dependent mitophagy. After the pharmacologic interventions of mitophagy, mitochondrial morphology and function have been restored, and cell viability has been further improved. Herein, we summarize the mitochondrial dysfunction and mitophagy alterations in obesity and diabetes, as well as the underlying upstream mechanisms, in order to provide novel therapeutic strategies for the obesity and diabetes-related heart disorders.

Objective:To report the use of right internal mammary artery (RIMA) in coronary artery bypass grafting (CABG) in our center, summarize the purpose and configuration of RIMA graft in CABG.Methods:All clinical data of coronary artery bypass grafting patients in our center performed in the past 6 years were collected and analyzed retrospectively. Those patients were divided into RIMA group and non-RIMA group according to the use of RIMA. Propensity score matching had been performed before these data was compared. Surgical technique of use of RIMA was summarized.Results:1 537 CABG had been performed from January 1st, 2016 to October 31st, 2021 in our center. Of which, 128 cases were allocated to RIMA group. After propensity score matching having been performed, there was no difference in baseline data between the RIMA group and the non-RIMA group (128 cases), and the RIMA group had more grafts and arterial grafts than the non-RIMA group. The postoperative drainage volume in the RIMA group was more than that of the non-RIMA group. However, there was no statistical significance in difference of transfusion between two groups. Also, there was no difference in postoperative mechanical ventilation time, ICU time and length of stay postoperatively. The postoperative complications were similar between two groups. Postoperative patency rate of the RIMA graft was as high as 95.2%. The target vessels of RIMA included left anterior descending branch (45 cases), diagonal branch (19 cases), intermediate branch (12 cases). obtuse marginal or circumflex branch (16 cases), posterior descending branch (5 cases) and right coronary trunk (18 cases). 41 RIMA used as free grafts, 87 used as in situ grafts, of which 19 RIMA need lengthened by other graft vessels.Conclusion:The patency rate of RIMA graft is high and the application of RIMA do not increase the surgical risk significantly. However, there are versatile contour of RIMA grafts. It can be used as artery graft in selected patients.