AIM:To investigate the effect of CYP2C19 gene polymorphism combined with plate-let function test guiding antiplatelet drug selection on gastrointestinal bleeding in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).METHODS:A total of 216 elderly patients with ACS who were admitted to our hospital from April 2021 to December 2022 and successfully completed PCI were selected and divided into study group and control group accord-ing to the random number table method,with 108 cases in each group.All patients received 4 days the same dose aspirin combined with clopidogrel antiplatelet therapy before surgery.After surgery,CYP2C19 genotype detection was performed on the study group to obtain genotype grouping to dis-tinguish different metabolites.Thromboelastogram(TEG)detection was performed on the patients with intermediate metabolites.According to the re-sults,patients with platelet inhibition rate less than 50％(clopidogrel resistance type)were selected and their medication was changed from aspirin and clopidogrel to aspirin and ticagrelor.The control group was treated with aspirin and clopidogrel.Se-rum levels of cardiac troponin(cTnl),creatine ki-nase isoenzyme(CK-MB)and hypersensitive C-reac-tive protein(hs-CRP)were observed 5 weeks after PCI,and major adverse cardiovascular events(MACE)were observed 1 and 6 months after PCI.The expression of CD62P and fibrinogen receptor 1(PAC-1)in platelets of the two groups were com-pared before and after 7 and 14 days of treatment.The platelet aggregation rate of the two groups was compared.Gastrointestinal bleeding events and cardiac emergencies were recorded after treat-ment.RESULTS:Genetic tests showed that there were 21 cases(19.44％)of ultrafast metabolites and 25 cases(23.15％)of fast metabolites,42 cases of abnormal metabolites including intermediate metabolites(genotypes accounting for 10.19％,13.89％,9.26％and 5.56％,respectively)and 20 cas-es of slow metabolites(genotypes accounting for 11,respectively).8.33％,7.41％and 2.78％).5 weeks after surgery,the serum levels of cTnl,hs-CRP and CK-MB in the study group were lower than those in the control group(P＜0.05,P＜0.01).One month after operation,the total incidence of MACE between the observation group and the control group was similar(P＞0.05).Six months after opera-tion,the total incidence of MACE in the observa-tion group was significantly lower than that in the control group(P＜0.05).The expression levels of CD62P and PAC-1 in the study group were lower than those in the control group on day 7 and day 14 after treatment(P＜0.01).The maximum platelet aggregation rate in the study group was lower than that in the control group(P＜0.01).The occurrence of cardiac emergencies between the two groups was similar(P＞0.05).The number of postoperative gastrointestinal bleeding in the study group was lower than that in the control group(x2=9.479,P＜0.01).CONCLUSION:Aspirin combined with ticagre-lor antiplatelet therapy can reduce platelet activity,aggregation rate and gastrointestinal bleeding events in patients with low response to chlorpyrro-lore who are co-screened by CYP2C19 genotype and platelet function test.

We chose Gaussia luciferase (Gluc), a secreted luciferase gene as reporter to real-time detect and dynamically monitor hydrodynamic injection gene expression. First, we constructed an expression vector pAAV2neo-Gluc. Then Huh7 and HepG2 cells were transfected with pAAV2neo-Gluc and the activity of Gluc in the supernatant and cell lysates were assayed. Results showed that the Gluc activity in the supernatant was about 100 higher than that in cell lysates, indicating the expressed Gluc existing mainly as a secreted form as reported. Live bioluminescence imaging of mice hydrodynamic injected pAAV2neo-Gluc showed whole body distribution, while the pAAV2neo-Fluc primarily located in the liver. Then we injected different doses of pAAV2neo-Gluc into mice by tail-vein hydrodynamic injection, took minor amount of blood from mice tails at different time points and measured the luciferase activity to investigate dynamic changes of Gluc expression and secretion in vivo. The results suggested that the time courses of Gluc expression were highly consistent among each dose groups. The luciferase activity in blood could be detected as early as 2 h after injection, reached the peak at about 10 h and gradually decreased from then on. The expression level of Glue was positively correlated with the dose of injected plasmid DNA. To further detect the assay sensitivity of the ex vivo Gluc measurement method, we investigated three additional groups of mice injected with lower doses of 0.001 microg, 0.01 microg and 0.1 microg pAAV2neo-Gluc respectively. Results revealed that activity of Gluc in blood could be detected even at dose as low as 0.001 microg DNA, suggesting the assay sensitivity was extremely high. In conclusion, a real-time ex vivo detection method of dynamically monitoring of gene expression in vivo by hydrodynamic injection can be a valuable means for the study of gene expression regulation in vivo.
Animals ; Gene Expression Regulation ; Genes, Reporter ; genetics ; Genetic Therapy ; Hep G2 Cells ; Humans ; Hydrodynamics ; Injections, Intravenous ; Liver ; metabolism ; Luciferases ; administration & dosage ; biosynthesis ; genetics ; pharmacokinetics ; Male ; Mice ; Mice, Inbred BALB C ; Transfection

The current finite element analysis of vascular stent expansion does not take into account the effect of the stent release pose on the expansion results. In this study, stent and vessel model were established by Pro/E. Five kinds of finite element assembly models were constructed by ABAQUS, including 0 degree without eccentricity model, 3 degree without eccentricity model, 5 degree without eccentricity model, 0 degree axial eccentricity model and 0 degree radial eccentricity model. These models were divided into two groups of experiments for numerical simulation with respect to angle and eccentricity. The mechanical parameters such as foreshortening rate, radial recoil rate and dog boning rate were calculated. The influence of angle and eccentricity on the numerical simulation was obtained by comparative analysis. Calculation results showed that the residual stenosis rates were 38.3%, 38.4%, 38.4%, 35.7% and 38.2% respectively for the 5 models. The results indicate that the pose has less effect on the numerical simulation results so that it can be neglected when the accuracy of the result is not highly required, and the basic model as 0 degree without eccentricity model is feasible for numerical simulation.