PURPOSE: To know whether the cardiac function of the patients with heart disease is impaired or improved after long-term taking ?-AR antagonists. METHODS: After giving the rats ?-AR selective antagonist, atenolol, for 12wk, the method of radioligand binding assay and the experiment of isolated left-atrium contractive function were carried out to observe the quantity and distribution of ?-AR, its subtypes, ?-AR, and the change of left - atrium contractive function. RESULTS: After long-term administration of atenolol, there were no any obvious changes in ?-AR, the density of the total ?-AR, ?1-AR, and the proportion of ?2-AR in tota1 amount of ?-AR, but the con centrat ion - response cu rves shi fted l e ftwa rd s si gn ifi cant ly as compared with control group- The PA2 value of isoprotenol(ISO) - induced positive inotropic effect after antagonized by ?1-AR selective antagonist CGP20712A in atenolol group was increased significantly as compared with control group. But the PKB value after antagonized by ICI 118511 showed no obvious difference between two groups. HPLC detection showed that the level of plasma atenolol was 3. 5pmol/L in atenolol group and the leveIs of plasma norepinephrine had no significant difference between two groups. But the level of plasma adrenaline in atenolol group was obviously lower than that in control group. CONCLUSIO- N: The long-term administration of ?l-AR antagonist will cause significant increase of the sensitivity of heart ?-AR, especially ?1-AR to excitant ISO. But the number of ?-AR and its subtypes did not change significantly. Besides, after the long-term administration of ?1-AR antagonist atenolol, the level of plasma adrenaline in rats was much lower than that in control group.

Objective To explore the relationship between methylenetetra hydrofolate reduetase (MTHFR) C677T genotypo and unstable angina pectoris(UA) in Chinese population. Methods The study consisted of 90 UA cases (UA group), and an age- and sex- matched healthy control cases (control group, n = 90). PC R-RFLP was used to analyze polymorphism of the MTHFR C677T genotypo. The relationship between MTHFR C677T genotype and UA was observed. Results MTHFR 677C→T mutation was found in 30 of 90 patients with unstable angina pectoris (33.33%) and in 15 of 90 control subjects (16.67%). This difference was statistically significant (P<0.05). Conclusion MTHFR 677C→T mutation is closely related to the unstable angina poctoris.

Objective To explore the clinical efficacy of alirocumab combined with ybutimibe in acute ST segment elevation myocardial infarction(STEMI).Methods A total of 112 cases of STEMI patients were randomly divided into control group and study group,with 56 cases in each.All patients underwent PCI treatment after admis-sion.The control group received oral administration of atorvastatin after the surgery,while the study group received combined treatment of atorvastatin with alirocumab.After 6 months of maintenance treatment,the low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),triglycerides,total cholesterol,left ventricular ejection fraction(LVEF),early and late diastolic peak flow velocity ratio(E/A)of the mitral valve orifice,left ventricular end-systolic diameter(LVESD),N-terminal pro-brain natriuretic peptide(NT-proBNP),cardiac troponin I(cTnI),lipoprotein-associated phospholipase A2(Lp-PLA2),matrix metalloproteinase-9(MMP-9),interleukin-6(IL-6),thrombolysis in myocardial infarction(TIMI)flow grade,drug toxicity,and postopera-tive cardiovascular adverse events were compared between the two groups.Results After treatment,the level of LDL-C,triglycerides,and total cholesterol in both groups decreased,and more significant results were found inthe study group(P＜0.05).There was no significant difference in HDL-C between the two groups before and after treatment(P＞0.05).After treatment,LVEF and E/A in both groups increased,with more significantresults in the study group(P＜0.05).LVESD,NT-proBNP,cTnI,Lp-PLA2,MMP-9,and IL-6 in both groups decreased after treatment,with more significant resultsin the study group(P＜0.05).The proportion of TIMI Ⅲ grade in the study group was higher than that in the control group(P＜0.05),and there was no significant difference in the incidence of drug adverse reactions and postoperative cardiovascular adverse events between the two groups6 months after surgery(P＞0.05).Conclusion The combination of alirocumab and ybutimibe in the treatment of STEMI PCI patients is more helpful in reducing blood lipid levels,promoting blood flow perfusion and improving myocardial function,and has good safety.

OBJECTIVE To explore the clinical efficacy of dapagliflozin for stable coronary heart disease combined with heart failure （HF）. METHODS A prospective study method was employed. A total of 158 patients with stable coronary heart disease and HF admitted to our hospital from January 1， 2023， to January 1， 2024， were enrolled. Using a random number table method， they were divided into dapagliflozin group （n＝76） and conventional treatment group （n＝82）. All patients received conventional treatment， including diuretic， aspirin， losartan， metoprolol and statins. Patients in the dapagliflozin group were additionally administered Dapagliflozin tablets at a dose of 10 mg once daily on top of the conventional treatment. The treatment duration was six months. The changes in left ventricular ejection fraction （LVEF）， left ventricular end-systolic diameter （LVESD）， left ventricular end-diastolic diameter （LVEDD）， fasting blood glucose， N-terminal pro-brain natriuretic peptide （NT-proBNP）， the number of angina attacks， the duration of angina attacks， and lipoprotein-associated phospholipase A2 before and after treatment were compared between the two groups. The occurrence of adverse reactions such as renal dysfunction， liver dysfunction， urinary system infections， new-onset dialysis， hypotension and hypoglycemia was evaluated in the two groups during treatment. RESULTS During the study， 16 patients were lost to follow-up. Ultimately， 70 patients in the dapagliflozin group and 72 patients in the conventional treatment group completed the study. Before treatment， there were no statistically significant differences in the aforementioned indicators between the two groups （P＞0.05）. Compared with before treatment， after treatment， both groups showed significant shortening in LVESD and LVEDD， significant increases in LVEF， significant reductions in NT-proBNP and lipoprotein-associated phospholipase A2 levels， and significant reductions in the number of angina attacks and the duration of angina attacks （P＜0.05）； the improvements in the dapagliflozin group were more significant than those in the conventional treatment group （P＜0.05）. There was no statistically significant difference between the two groups in fasting blood glucose levels and the incidence of the aforementioned adverse reactions （P＞0.05）. CONCLUSIONS Adding dapagliflozin to conventional treatment can shorten LVESD and LVEDD， increase LVEF levels， reduce NT-proBNP and lipoprotein-associated phospholipase A2 levels， and decrease the number and duration of angina attacks in patients with stable coronary heart disease combined with HF， thereby improving their cardiac function， and demonstrates good safety.

OBJECTIVE: To assess the effect of tumor cell lysate (TCL) with low high-mobility group B1 (HMGB1) content for enhancing immune responses of dendritic cells (DCs) against lung cancer. METHODS: TCLs with low HMGB1 content (LH-TCL) and normal HMGB1 content (NH-TCL) were prepared using Lewis lung cancer (LLC) cells in which HMGB1 was inhibited with 30 nmol/L glycyrrhizic acid (GA) and using LLC cells without GA treatment, respectively. Cultured mouse DCs were exposed to different doses of NH-TCL and LH-TCL, using PBS as the control. Flow cytometry was used to detect the expressions of CD11b, CD11c and CD86 and apoptosis of the stimulated DCs, and IL-12 levels in the cell cultures were detected by ELISA. Mouse spleen cells were co-cultured with the stimulated DCs, and the activation of the spleen cells was assessed by detecting CD69 expression using flow cytometry; TNF-β production in the spleen cells was detected with ELISA. The spleen cells were then co-cultured with LLC cells at the effector: target ratios of 5:1, 10:1 and 20:1 to observe the tumor cell killing. In the animal experiment, C57/BL6 mouse models bearing subcutaneous LLC xenograft received multiple injections with the stimulated DCs, and the tumor growth was observed. RESULTS: The content of HMGB1 in the TCL prepared using GA-treated LLC cells was significantly reduced (P < 0.01). Compared with NH-TCL, LH-TCL showed a stronger ability to reduce apoptosis (P < 0.001) and promote activation and IL- 12 production in the DCs. Compared with those with NH-TCL stimulation, the DCs stimulated with LH-TCL more effectively induced activation of splenic lymphocytes and enhanced their anti-tumor immunity (P < 0.05). In the cell co-cultures, the spleen lymphocytes activated by LH-TCL-stimulated DCs showed significantly enhanced LLC cell killing activity (P < 0.01). In the tumor-bearing mice, injections of LH-TCL-stimulated DCs effectively activated host anti-tumor immunity and inhibited the growth of the tumor xenografts (P < 0.05). CONCLUSION Stimulation of the DCs with LH-TCL enhances the anti-tumor immune activity of the DCs and improve the efficacy of DCbased immunotherapy for LLC in mice.
Animals ; Humans ; Mice ; Apoptosis ; Dendritic Cells/immunology* ; Glycyrrhizic Acid/pharmacology* ; HMGB1 Protein ; Lung Neoplasms/immunology*

OBJECTIVE To conduct the pharmacoeconomic evaluation of empagliflozin in the treatment of heart failure with reduced ejection fraction （HFrEF），and to provide evidence-based reference for rational drug use and medical and healthy decision-making. METHODS A Markov model was used to perform a cost-effectiveness analysis of the regimen of empagliflozin in the treatment of HFrEF ，and to evaluate the cost and effectiveness of standard treatment plan plus empagliflozin （empagliflozin group）vs. standard treatment plan （standard treatment group ）. Clinical parameters were obtained from the EMPEROR-Reduced study；cost and utility data came from the published literatures. The cycle of the model was 1 month and the simulation time was 20 years. Single-factor sensitivity analysis and probability sensitivity analysis were performed to validate the results of cost-effectiveness analysis. RESULTS Compared with the standard treatment group ，each additional quality-adjusted life year in the empagliflozin group cost 37 995.94 yuan more ，which was less than China ’s 1 time GDP per capita in 2020（72 447 yuan）. The results of single factor sensitivity analysis showed that steady-state hospitalization rate of 2 groups was the most important factor affecting the incremental cost-effectiveness ratio . The results of probability sensitivity analysis showed that when the willingness-to-pay threshold （WTP）was 1 time GDP per capita in 2020（72 447 yuan），the probability of empagliflozin group with cost-effectiveness advantage was 58.8％；when the WTP was 3 times GDP per capita in 2020（217 341 yuan），the probability of empagliflozin group with cost-effectiveness advantage was 63.8％. CONCLUSIONS Compared with standard treatment plan alone，standard treatment plan plus empagliflozin is more cost-effective in the treatment of HFrEF. However ，the economic probability is not high.