Development and validation of risk prediction model for new-onset cardiovascular diseases among breast cancer patients: Based on regional medical data of Inner Mongolia / 北京大学学报(医学版)

OBJECTIVE@#To develop and validate a three-year risk prediction model for new-onset cardiovascular diseases (CVD) among female patients with breast cancer.@*METHODS@#Based on the data from Inner Mongolia Regional Healthcare Information Platform, female breast cancer patients over 18 years old who had received anti-tumor treatments were included. The candidate predictors were selected by Lasso regression after being included according to the results of the multivariate Fine & Gray model. Cox proportional hazard model, Logistic regression model, Fine & Gray model, random forest model, and XGBoost model were trained on the training set, and the model performance was evaluated on the testing set. The discrimination was evaluated by the area under the curve (AUC) of the receiver operator characteristic curve (ROC), and the calibration was evaluated by the calibration curve.@*RESULTS@#A total of 19 325 breast cancer patients were identified, with an average age of (52.76±10.44) years. The median follow-up was 1.18 [interquartile range (IQR): 2.71] years. In the study, 7 856 patients (40.65%) developed CVD within 3 years after the diagnosis of breast cancer. The final selected variables included age at diagnosis of breast cancer, gross domestic product (GDP) of residence, tumor stage, history of hypertension, ischemic heart disease, and cerebrovascular disease, type of surgery, type of chemotherapy and radiotherapy. In terms of model discrimination, when not considering survival time, the AUC of the XGBoost model was significantly higher than that of the random forest model [0.660 (95%CI: 0.644-0.675) vs. 0.608 (95%CI: 0.591-0.624), P < 0.001] and Logistic regression model [0.609 (95%CI: 0.593-0.625), P < 0.001]. The Logistic regression model and the XGBoost model showed better calibration. When considering survival time, Cox proportional hazard model and Fine & Gray model showed no significant difference for AUC [0.600 (95%CI: 0.584-0.616) vs. 0.615 (95%CI: 0.599-0.631), P=0.188], but Fine & Gray model showed better calibration.@*CONCLUSION@#It is feasible to develop a risk prediction model for new-onset CVD of breast cancer based on regional medical data in China. When not considering survival time, the XGBoost model and the Logistic regression model both showed better performance; Fine & Gray model showed better performance in consideration of survival time.

Human bone marrow derived multipotent adult progenitor cells differentiating into hepatocyte-like cells after being induced by co-culturing with human hepatocyte line L02 / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the possibility of marrow derived multipotent adult progenitor cells (MAPCs) differentiating into hepatocytes by co-culturing with human hepatocyte line L02, and to evaluate the potential use of MAPCs in tissue-engineering either experimentally or clinically.</p><p><b>METHODS</b>(1) Co-culturing without cell-to-cell contact: MAPCs and L02 hepatocytes were spread on coverslips separately (both with a cell density of 1x10(5)/ml), and then they were put in a culture dish (10 cm). The expressions of Alb, AFP, CK18, and CK19 in MAPCs were detected by immunocytochemistry at different time points. A separate culture of L02 hepatocytes served as a positive control and a separate culture of MAPCs served as a negative control. (2) Co-culturing with cell-to-cell contact: MAPCs labeled with CFSE were mixed with L02 hepatocytes (both with a cell density of 1x10(4)/ml), and then the mixed cells were seeded on specific dishes for detection by laser scanning confocal microscope (LSCM). Five days later, the cells were double-stained with SABC-Cy3. The expressions of Alb, AFP, CK18 in MAPCs were observed under LSCM. Similarly, separately cultured L02 hepatocytes served as a positive control and separately cultured MAPCs served as a negative control.</p><p><b>RESULTS</b>(1) Results of co-culturing without cell-to-cell contact: On the first day, the MAPCs expressed a high level of AFP. Then AFP expression tapered daily and there was hardly any expression of AFP on day 7. The expression of Alb was very weak on day 1, but increased significantly by day 3, reached its peak on day 5, and still maintained a high level on day 7. The initial expression of CK18 appeared on day 5 and reached a higher level on day 7. The expression of CK19 was always negative. The positive control cells had a high expression of Alb and CK18, while there was a weak expression of AFP and a negative expression of CK19. The negative control cells had no expressions for the four markers. (2) Results of co-culturing with cell-to-cell contact: On day 5, there were three colors of fluorescence under LSCM: yellow cells were MAPCs differentiating into hepatocytes; green cells were undifferentiated MAPCs; red cells were L02 hepatocytes. The result showed that Alb and CK18 were expressed in many cells and AFP appeared in only a few cells.</p><p><b>CONCLUSION</b>Human MAPCs can be induced to differentiate into mature hepatocyte-like cells by co-culturing with L02 hepatocytes, either with or without cell-to-cell contact, but the former way may be more effective.</p>