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.

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.

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.

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Objective To discuss the microstructure and properties of vascular puncture with a blunt needle Pix'L filling injection.Methods Scanning electron microscopy (SEM) and photoelectron spectroscopy were employed for the analysis of the different morphology and elements,and a rat model was established to study thrusts of different microcannulas and hypodermic needle when stabing vessels.Ultimately we analyzed the correlation between the morphology and puncture force of different microcannulas.Results The SEM images of microcannulas from different manufacturers were different,and revealed the different technics of different manufacturers.Puncture forces of different microcannulas corresponded to the cross-section and smooth degree of the tips.Conclusions The SEM morphology and puncture force of microcannulas from different manufacturers are different,which indicate the different characters and usability.Plastic surgeons should select to use them more judiciously.

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.

Objective To investigate the role of human umbilical cord mesenchymal stem cell-derived extracellular vesicle (hUC-MSC-EV) in the regeneration of fibrotic liver. Methods C57BL/6 mice were randomly divided into the 70% normal liver resection group (Oil+PHx group), 70% liver fibrosis resection group (CCl₄+PHx group) and 70% liver fibrosis resection+mesenchymal stem cell-derived extracellular vesicle (MSC-EV) treatment group (CCl₄+PHx+MSC-EV group), with 8 mice in each group. LX-2 cell lines were assigned into the phosphate buffer solution (PBS) group, transforming growth factor (TGF)-β group and TGF-β+MSC-EV group. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in mice after partial liver resection were detected in each group. The expression levels of liver fibrosis and proliferation-related parameters were analyzed in each group. The messenger RNA (mRNA) expression levels of epidermal growth factor (EGF), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in LX-2 cells were detected in each group, and their effects on HGF expression in mouse liver were observed. Results Compared with the Oil+PHx group, the serum levels of AST, ALT and LDH were up-regulated, and the degree of fibrosis was more severe, the positive area of Sirius red and α-smooth muscle actin (α-SMA) staining was larger, and the expression level of α-SMA protein was up-regulated in the CCl₄+PHx group. Compared with the CCl₄+PHx group, the serum levels of AST, ALT and LDH were decreased, the degree of fibrosis was slighter, the positive area of Sirius red and α-SMA staining was decreased, and the expression level of α-SMA protein was down-regulated in the CCl₄+PHx+MSC-EV group, and the differences were statistically significant (all P < 0.05). Compared with the Oil+PHx group, the protein expression levels of Ki67 and proliferating cell nuclear antigen (PCNA) were lower in the CCl₄+PHx group. Compared with the CCl₄+PHx group, the protein expression levels of Ki67 and PCNA were increased in the CCl₄+PHx+MSC-EV group, and the differences were statistically significant (all P < 0.05). Compared with the PBS group, the expression level of CollagenⅠ mRNA in LX-2 cells was increased, the expression level of α-SMA protein was up-regulated and the expression level of HGF protein was decreased in the TGF-β group. Compared with the TGF-β group, the expression level of CollagenⅠ mRNA in LX-2 cells was decreased, the expression levels of HGF mRNA and protein were increased, and the expression level of α-SMA protein was decreased in the TGF-β+MSC-EV group, the differences were statistically significant (all P < 0.05). The expression level of HGF protein in the CCl₄+PHx group was lower than that in the Oil+PHx group, whereas the difference was not statistically significant (P > 0.05). The expression level of HGF protein in the CCl₄+PHx+MSC-EV group was higher than that in the CCl₄+PHx group, and the difference was statistically significant (P < 0.05). Conclusions The regenerative capacity of fibrotic liver is weaker than that of normal liver. hUC-MSC-EV may alleviate liver fibrosis and improve liver regeneration by promoting HGF secretion from actived hepatic stellate cells and effectively enhancing the regenerative capacity of fibrotic liver.

With the rapid development of modern economy, road traffic has become increasingly busy, and the accompanying environmental pollution problem is becoming increasingly prominent. Air pollutants emitted from automobile exhaust, including particulate matters, NO_x, CO, and hydrocarbons (PAHs), can cause high risk of cardiovascular disease and premature death. This article summarizes the related epidemiological research progress on this topic from published literatures in recent years. We reviewed acute and chronic health damage to the cardiovascular system caused by traffic related air pollutants, including changes in heart rate variability and blood system indicators, potential association with coronary arteriosclerosis, coronary heart disease, and death of cardiovascular disease. The results show that traffic-related air pollutants can cause decrease in heart rate variability, increased blood pressure and changes in blood indicators, increase acute mortality from cardiovascular diseases. Long-term exposure to traffic-related air pollutants can induce increased risk of coronary atherosclerosis and coronary heart disease, and lead to increased mortality from cardiovascular diseases. In the future, more attention should be paid to traffic-related air pollution, and more researches are recommended to comprehensively evaluate the relationship between traffic-related air pollution and cardiovascular health damages, especially in early-stage. At the same time, active researches on the mechanism of cardiovascular toxicity of traffic-related air pollutants are needed, so as to promote the early prevention of cardiovascular diseases.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common human cancers; however, its outcome of pharmacotherapy is always very limited. Herein, we performed a batch query in the connectivity map (cMap) based on bioinformatics, queried out 35 compounds with therapeutic potential, and screened out parbendazole as a most promising compound, which had an excellent inhibitory effect on the proliferation of HNSCC cell lines. In addition, tubulin was identified as a primary target of parbendazole, and the direct binding between them was further verified. Parbendazole was further proved as an effective tubulin polymerization inhibitor, which can block the cell cycle, cause apoptosis and prevent cell migration, and it exhibited reasonable therapeutic effect and low toxicity in the in vivo and in vitro anti-tumor evaluation. Our study repositioned an anthelmintic parbendazole to treat HNSCC, which revealed a therapeutic utility and provided a new treatment option for human cancers.