Aim To investigate the direct effects and mechanism of carvedilol on HERG channel stably expressing in human embryonic kidney-293(HEK293) cells.Methods Whole-cell patch-clamp technique was used to record HERG current and kinetic curves in single cells.Western blot methods were used to investigate the expression of HERG channel in different concentration of carvedilol.Result Carvedilol decreased HERG current in a concentration-dependent manner with an IC50 539.6 nmol?L-1,Hillslope-0.64.The time constants of onset of inactivation and deactivation were accelerated.Other kinetcs(activation,inactivation,recovery from inactivation)had no significant changes.Based on western result,carvedilol had no effect on the generation and trafficking of HERG protein.Conclusion Carvedilol inhibits the transfected HERG channels by influencing the open state which is the probable anti-arrhythmic mechanism.There is no relationship between carvedilol and HERG channel expression.

The aim of this study was to investigate the effect of Paris saponin I (PS I) on human gastric carcinoma cell growth and apoptosis and to explore the potential mechanisms. The proliferation of SGC7901 cells was monitored by the MTT cell viability assay, while the nuclear morphology of apoptotic cells was assessed by Hoechst 33258 staining. Flow cytometry was performed to analyze the cell cycle progression of propidium iodide (PI)-stained SGC7901 cells and the apoptotic rate of annexin V/PI-stained cells. Western blotting was used to examine the expression of several cell cycle proteins, including cyclin B1 and Cdk1, and the apoptosis-regulated proteins Bcl-2, Bax, cytochrome c, procaspase-9, and procaspase-3. The MTT assay demonstrated that PS I could induce significant dose- and time-dependent inhibition of SGC7901 cell proliferation. Marked morphological changes, including condensation of chromatin, nuclear fragmentation and apoptotic bodies were clearly shown on Hoechst 33258 staining. PSI treatment also resulted in the disruption of the cell cycle at G(2)/M and the induction of apoptosis. Following PSI treatment, the cell cycle-related proteins cyclin B1 and Cdk1 were down-regulated. Expression of the pro-apoptotic protein Bax was increased, while anti-apoptotic protein Bcl-2 decreased. PSI treatment resulted in elevated cytoplasmic cytochrome c and activation of the apoptotic proteases caspase-9 and caspase-3. These data indicate that PS acts as an inhibitor of proli I feration in SGC7901 cells by inducing cell cycle arrest and mitochondria-dependent apoptosis. PSI is a potential therapeutic agent against human gastric carcinoma.

ObjectiveTo investigate the efficacy of raltitrexed combined with transcatheter arterial chemoembolization (TACE) in the treatment of advanced colorectal cancer with liver metastasis. MethodsA total of 80 patients with liver metastasis of advanced colorectal cancer who were admitted to Central Hospital of China National Petroleum Corporation and underwent surgery from January 2012 to June 2015 were enrolled and randomly divided into study group and control group, with 40 patients in each group. The patients in the study group underwent hepatic arterial infusion chemotherapy with raltitrexed combined with TACE, and those in the control group were treated with intravenous infusion of raltitrexed alone. The above treatment was performed once every 4 weeks for 3-6 cycles. The response rate (RR), disease control rate (DCR), median time to disease progression, survival rate, and reductions in carcinoembryonic antigen (CEA), CA19-9, aminotransferases, and bilirubin were observed in the two groups. The chi-square test was used for comparison of categorical data between groups. ResultsRR, DCR, and the median time to disease progression showed significant differences between the study group and the control group (45.0% vs 22.5%, χ2=4.528, P=0.033; 70.0% vs 47.5%, χ2=4.178, P=0.041; 17.9 months vs 10.5 months, χ2=2408, P＜0.001). The study group had significantly higher 1- and 2-year survival rates than the control group (80.0% vs 57.5%, χ2=4.713, P=0.030; 55.0% vs 32.5%, χ2=4.114, P=0.043). The study group had a significantly higher number of patients with more than 50% reductions in CA19-9, CEA, aminotransferases, and bilirubin at 2 months after TACE than the control group (χ2=5333, 4528, 5051, and 5.013, P=0.021, 0.033, 0.025, and 0.025). ConclusionRaltitrexed combined with TACE is of good value in the treatment of advanced colorectal cancer with liver metastasis and holds promise for clinical application.

The aim of this study was to investigate the effect of Paris saponin Ⅰ (PS Ⅰ ) on human gastric carcinoma cell growth and apoptosis and to explore the potential mechanisms.The proliferation of SGC7901 cells was monitored by the MTT cell viability assay,while the nuclear morphology of apoptotic cells was assessed by Hoechst 33258 staining.Flow cytometry was performed to analyze the cell cycle progression of propidium iodide (PI)-stained SGC7901 cells and the apoptotic rate of annexin V/PI-stained cells.Western blotting was used to examine the expression of several cell cycle proteins,including cyclin B1 and Cdkl,and the apoptosis-regulated proteins Bcl-2,Bax,cytochrome c,procaspase-9,and procaspase-3.The MTT assay demonstrated that PSⅠ could induce significant doseand time-dependent inhibition of SGC7901 cell proliferation.Marked morphological changes,including condensation of chromatin,nuclear fragmentation and apoptotic bodies were clearly shown on Hoechst 33258 staining.PSⅠ treatment also resulted in the disruption of the cell cycle at G2/M and the induction of apoptosis.Following PSⅠ treatment,the cell cycle-related proteins cyclin B 1 and Cdk1 were downregulated.Expression of the pro-apoptotic protein Bax was increased,while anti-apoptotic protein Bcl-2decreased.PSⅠ treatment resulted in elevated cytoplasmic cytochrome c and activation of the apoptotic proteases caspase-9 and caspase-3.These data indicate that PSⅠ acts as an inhibitor of proliferation in SGC7901 cells by inducing cell cycle arrest and mitochondria-dependent apoptosis.PSⅠ is a potential therapeutic agent against human gastric carcinoma.

Objective:To investigate the satisfaction of clinical interns to the department and teachers under the merging mode of standardized residency training and clinical practice, and to explore the feasibility to further implement the mode in clinical practice.Methods:Cluster sampling was used to design the scale, which included the importance attached by department to the teaching work, the rationality of the arrangement of practice content, the implementation of teaching activities, the quality of teaching activities, the status of out-department examination, the demonstration of medical ethics of teachers, the teaching attitude and knowledge lecturing of teachers, the revision of medical records and the guidance of skills operation, etc. The questionnaire survey was conducted among clinical interns in a hospital from July 2018 to June 2019. SPSS 22.0 was used to conduct t test or rank sum test of two independent samples, and the analysis of multiple groups of data was performed by means of variance analysis. Results:A total of 1 230 questionnaires were sent out, and 1 195 were returned, with an effective recovery rate of 97.15%. The overall satisfaction of interns was (9.62±0.39). The interns gave the highest evaluation on the medical ethics and medical style of the teacher (9.75±0.78), and the lowest evaluation on the teaching quality of all departments (9.52±1.15). There were significant differences among the evaluations ( F=7.30, P<0.001). Conclusion:Under the merging mode of standardized residency training and clinical practice management, all teaching and research sections and departments have fulfilled various teaching tasks according to the requirements, but the teaching quality and connotation construction need to be further strengthened.