Résumé
@#Human intestinal absorption (HIA) is a crucial indicator for measuring the oral bioavailability of drugs.This study aims to use artificial intelligence methods to predict and evaluate the HIA of drugs in the early stages of drug discovery, thus accelerating the drug discovery process and reducing costs.This study used MOE''s 2D, 3D descriptors, and ECFP4 (extended connectivity fingerprints) to characterize the molecules and established eight models, including support vector machine (SVM), random forest (RF), and deep neural network (DNN).The results showed that the SVM model constructed using a combination of 2D, 3D descriptors and ECFP4 fingerprints was the optimal model according to comprehensive evaluation of various evaluation indicators.The area under the receiver operating characteristic curve (AUC), Matthews correlation coefficient, and Kappa coefficient of the optimal model were 0.94, 0.75, and 0.74, respectively.In conclusion, this study established a robust and generalizable machine learning model for predicting HIA properties, which can provide guidance for early molecular screening and the study of pharmacokinetic properties of drugs.
Résumé
Objective To explore the feasibility of repairing skin defect with Pelnac tissue engineering skin and cultured epidermal stem cells ( ESCs) and fibroblasts. Methods ESCs and fibroblasts in SD rats were isolated and cultured in vitro, and then were detected by immunohistochemistry. Fibroblasts were seeded in Pelnac material to construct dermis, and ESCs were seeded on the surface of dermis to construct tissue engineering skin. Thirty BALC/c nude mice were randomly divided into groups A, B and C. After mouse back skin defect model was established, group A was transplanted with Pelnac material, group B was transplanted with compound of Pelnac and fibroblasts, and group C was transplanted with Pelnac tissue engineering skin. The wound healing was observed after operation. The wound tissues were sampled for pathological histology test on the 5th and 7th day after transplantation. Results The expression of cytokeratin 15 and β1 integrin in ESCs was positive, and the expression of laminin ( LN) and fibronectin ( FN) in fibroblasts was positive. In group C, the wound healing of nude mice was the best, characterized by the proliferation of fibroblasts, obvious new capillaries and regularly arranged epidermal cells at the transplantation sites. Conclusion Pelnac tissue engineering skin has good effects on promoting repair of skin defect of nude mice.
Résumé
Objective To analyze the clinical symptoms,pathological features and K-ras mutation alterations of intraductal tubulopapillary neoplasm (ITPN),and to better understand ITPN.Methods We collected the clinical data of 3 cases of ITPNs of Changhai Hospital and 16 cases in literature,and analyzed the morphology,K-ras mutation,immunophenotype of tumor cells by routine H&E staining,immonohistochemistry,and fluorescence PCR.Then it was compared with 81 cases of intraductal papillary mucinous tumor (IPMT).Results All the 3 patients of ITPN were male,with a median age of 43 years.Two lesions were located in pancreatic head and 1 case in pancreatic body and tail.ITPNs presented as intraductal solid masses,and consisted of cells with uniformly median-to-high grade nuclear atypia,and tumor cells were arranged as glandular and cribriform.One case was accompanied with invasive ductal adenocarcinoma and peripancreatic lymph node metastasis.All tumor cells of epithelial marker cytokeratin was positively expressed,and p53 was positively expressed in some tumor cells.However,CHR,NSE,MUC2 and MUC5AC were negatively expressed,and K-ras mutation was not detected.The tumor cells of IPMT were presented as papillary pattern and cribriform structure was observed.The majority of cells were mucous epithelium,or goblet cells (intestinal type),a few were eosinophilic epithelium (eosinophilic cells type) and cuboidal epithelium (pancreatic,biliary duct type),MUC2 and MUC5AC was positively expressed,and K-ras mutation rate was 50％.Conclusions As a new tumor entity of pancreas,ITPNs show distinctive features with IPMTs.
Résumé
Objective To establish a simple , practical , highly-effective and stable method for the isolation and cultivation of rat hair follicle cells. Methods Under sterile condition, single hair follicle was taken out after the skin around the barbel of SD neonatal rats was sheared off. And then the hair follicles were digested with two-step method with Type Ⅰcollagenase and trypsin. The obtained cell suspension was planted into the culture plate which was covered with extracellular matrix, and then was cultivated with K-SFM culture medium containing fetal bovine serum with volume fraction of 1%. On the next day, K-SFM culture medium was replaced with serum-free culture medium. The remaining tissues were cut into pieces and spread out in the culture flask, and then were cultivated with HG-DMEM culture medium containing serum. Two kinds of cells were harvested and then were identified by immunofluorescence. The hair follicle epithelial cells were tested by flow cytometer. Results The hair follicle epithelial cells obtained through the above methods showed rapid adherence, and were round or polygon-like , with typical cobblestone-like morphology. The long spindle-shaped cells were seen around the tissues cultivated, having many protrusions on the surface of the cells, and they were interconnected into reticular structure. The expression of cytokeratin 15, cytokeratin 19 and β1 integrin in epithelial cells were positive. Most of the epithelial cells were in the G1 phase, accounting for 75.6%. The expression of laminin ( LN), fibronectin ( FN) and vimentin in the connective tissue sheath cells were also positive. Conclusion The cells harvested by modified two-step enzyme digestion method have confirmed as hair follicle cells and fibroblasts, and the obtained cells are of rapid adherence, good homogeneity, and active proliferation.