Objective: To investigate the action and antioxidant effects of CB2 agonist AM-1241 on rat hepatic stellate cell line (HSC-T6). Methods: HSC-T6 was randomly divided into four groups: control group, oxidative stress group, AM-1241 intervention group and AM-1241+AM-630 antagonist group. Survival rate of HSC-T6 was detected by thiazolyl blue assay under 24 h interventions with 0, 20, 50, 80 μmol/L AM-1241 and 0, 10, 20, 30, 40 μmol/L AM-630, respectively. Besides control group, the remaining groups were well cultured in low-glucose DMEM containing 100 mU/L glucose oxidase (GO) for 12 h to prepare the oxidative stress model. Then, AM-1241 intervention group was treated with 50 μmol/L low-glucose DMEM medium. After incubation for 12 h, the AM-1241+AM-630 antagonist group was treated with CB2 antagonist AM-630 (20 μmol/L) for 2 h, and cultured with 50 μmol/L AM-1241 in complete low-glucose medium for 12 h. The optimal drug concentration was selected according to the cell viability considered by the experiment results. Type III collagen (C III) content in the HSC-T6 supernatant was detected by enzyme-linked immunosorbent assay. Glutathione (GSH) content in HSC-T6 was detected by spectrophotometry. CB2 and heme oxygenase-1(HO-1) in each group of HSC-T6 were detected by western blotting. Results: HSC-T6 proliferation was inhibited in each group of AM-1241 in a concentration-dependent manner (P < 0.05). The inhibition was highest at 80μmol/L, and the cell survival rate was (41.61% ± 3.13%) (P < 0.05). AM-630 concentration group had no significant inhibitory effect on the proliferation of HSC-T6 (P > 0.05). HSC-T6 expressed CB2 receptor in each group. The expression level of CB2 in the AM-1241 intervention group was higher compare with control group (P < 0.05).The expression of Col III were significantly higher in oxidative stress group (P < 0.05) than in control group, and the expression of Col III of AM-1241 intervention group was significantly lower than that in oxidative stress group (P < 0.05). Col III level in AM-1241+AM-630 antagonistic group was significantly higher than that in AM-1241 intervention group (P < 0.05). There was no significant difference between AM-1241+AM-630 antagonistic group and oxidative stress group (P > 0.05). The content of GSH and HO-1 in oxidative stress group was higher (P < 0.05) than control group. The content of GSH and HO-1 in the AM-1241 intervention group was higher compared with oxidative stress group, while content of AM-1241 + AM-630 antagonist group was lower compared to AM-1241 intervention group (P < 0.05), and the differences were not statistically significant for oxidative stress group. Conclusion CB2 agonist AM-1241 can inhibit the proliferation and activation of HSC-T6 and its mechanism may activate the nuclear translocation of Nrf2 binding to HSC-T6, initiating the up-regulation of antioxidant enzymes HO-1 and GSH protein expression, and thus increase the antioxidant effect of HSC-T6.

Objective:To evaluate the safety of leadless pacemaker implantation in super-elderly patients.Methods:Eleven patients with average age of 90 (86, 92) years who underwent leadless pacemaker implantation in the Department of Cardiology, Peking University People′s Hospital from March 2021 to May 2022 were included. The clinical data and implantation information were collected. The complications (cardiac tamponade, myocardial infarction, cerebral infarction, pulmonary embolism, pacemaker reinfection, femoral vein hematoma) and death of patients were documented at 24 h, 3 d, and 1, 3, 6 months after pacemaker implantation.Results:There were 9 males and 2 females with the body mass index of 21(19, 23)kg/m 2. The underlying diseases were hypertension, diabetes, coronary heart disease, chronic kidney disease, chronic obstructive pulmonary disease, previous cerebral infarction and moderate to severe tricuspid regurgitation in 9, 9, 9, 6, 4, 4, 4 patients, respectively. The left ventricular ejection fraction was 49% (45%, 52%), the hemoglobin concentration was 118 (114, 122)g/L, 4 patients were taking anticoagulant drugs, and 6 patients were taking antiplatelet drugs. Eight patients were newly implanted with a leadless pacemaker, 2 patients were implanted after removal the old ones, and 1 case was implanted at the same time as removal. The implantation time was 45(40, 47) minutes, the X-ray exposure time was 14 (13, 15) minutes, the release time was 1 (1, 2), the threshold value was 0.50(0.38, 0.75)V/0.24 ms, the impedance was 730 (700, 770) Ω, and the perceived R-wave amplitude 8.2(6.7, 12.8) mV. During the follow-up period of 8 (6, 10) months, no patient had pacemaker dysfunction; and the threshold, R wave sensing, and impedance were stable and maintained within the normal range. No cardiac tamponade, myocardial infarction, cerebral infarction, pulmonary embolism, pacemaker reinfection or death occurred perioperatively and during the follow-up period; 1 patient had hematoma after femoral vein puncture, which improved after compression treatment. Conclusion:This single-center and small-sample study shows that leadless pacemaker implantation is safe for super-elderly patients.

Objectives:To evaluate the safety and efficacy of implantation of subcutaneous implantable cardioverter defibrillator(S-ICD)after transvenous lead extraction(TLE)in ICD patients without pacing indications. Methods:All patients who underwent TLE at Peking University People's Hospital from June 2018 to October 2023 were consecutively included.TLE indication,S-ICD implantation indication,defibrillation threshold(DFT)test,complications and postoperative follow-up were collected and analyzed. Results:A total of 11 patients with TV-ICD underwent S-ICD implantation after TLE,eight patients were males and median age were 56(44,65)years.The indications for TLE were infection and lead dysfunction.Nine patients were implanted with S-ICD for secondary prevention,and the most common cause of implantation was ion channelopathies(5 cases).The operative time for S-ICD was 51(48,58)minutes and no perioperative complications were noted.Eight patients underwent DFT testing,and 100%were successful.During a median follow up of 30(9,39)months,a total of six appropriate treatments occurred in two patients,and no complications occurred,including inappropriate treatment,ineffective treatment,infection,lead malfunction and death. Conclusions:Our study provides evidence for S-ICD implantation as a replacement after TV-ICD removal.The S-ICD implantation after TLE is safe and effective.