Objective : To predict and validate key targets for cisplatin(DDP) resistance in colorectal cancer(CRC) to provide more options for precision medicine in clinical treatment. Methods: Differentially expressed genes(DEGs) between normal colonic mucosa and CRC were screened from the gene expression omnibus(GEO) database. Key genes were identified using the STRING database and Cytoscape software. DEGs were subjected to enrichment analysis using the gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) databases. Key targets were validated through RNA-seq, qRT-PCR, and Western blot. The versican(VCAN) gene overexpression vector was transfected into human ileocecal colorectal adenocarcinoma cell line HCT8, and cell viability was assessed using the CCK-8 assay. Flow cytometry was used to assess apoptosis and cell cycle distribution. qRT-PCR and Western blot were performed to detect mRNA and protein levels of the target genes. Results : In this study, 118 upregulated DEGs and 146 downregulated DEGs were identified from the GEO database. DEGs were mainly enriched in extracellular matrix degradation, extracellular matrix organization, and the phosphoinositide 3-kinase(PI3K)-protein kinase B(AKT) signaling pathway. Based on protein-protein interaction network analysis, 20 hub genes were identified. By comparing the transcriptome sequencing results of the HCT8 parental strain and DDP-resistant strain, the VCAN gene was further selected. In CRC tissues, the expression level of VCAN was higher than that in normal colonic mucosa, and patients with high VCAN expression had shorter overall survival(OS) and recurrence free survival(RFS) times. Overexpression of VCAN in CRC cells promoted cell proliferation(P<0.05), increased resistance to DDP, reduced DDP-induced apoptosis(P<0.05), and G0/G1phase arrest(P<0.05); upregulation of VCAN activated the protein kinase B(AKT)-mammalian target of rapamycin(mTOR) signaling pathway. Conclusion Bioinformatics and transcriptome sequencing identified VCAN as a key target gene for DDP resistance in CRC, potentially promoting CRC progression and DDP resistance by regulating the AKT-mTOR pathway.

OBJECTIVE： To prepare Melatonin solid lipid nanoparticles （MT-SLNs）， and to investigate in vitro transcutaneous absorption characteristics of them in isolated skin of mice. METHODS： Using melatonin （MT） as model drug， glycerin sorbate as oil phase， poloxamer 188 （F188） as emulsifier， MT-SLNs was prepared by melt-emulsion method. The morphology of MT-SLNs was observed by TEM； the particle size distribution of MT-SLNs was measured by laser particle size analyzer， and the infrared spectrum characteristics were measured by infrared spectroscopy. The entrapped efficiency and drug loading amount were determined by HPLC and ultrafiltration centrifugation method. The transcutaneous absorption characteristics in vitro of MT-SLNs and MT raw material were compared using Franz diffusion cells method. RESULTS： The formulation of MT-SLNs included 2.5 mg/mL MT raw material， 25 mg/mL glycerin sorbate and 1％F188. The obtained MT-SLNs were spherical， and no aggregation was observed. Average particle size was （67.88±0.17）nm， and polydispersity index was 0.188±0.001. The characteristic absorption peaks of N—H stretching and bending vibration were not found in infrared spectra， and the characteristic absorption peaks of C—H stretching vibration of benzene ring shifted red to 1 750 cm－1. The entrapped efficiency and drug loading amount of MT-SLNs were （87.54±5.31）％ and （8.42±0.78）％. The transcutaneous absorption behavior of MT-SLNs and MT raw material conformed to zero-order kinetics release rule. The steady-state transmission rate of MT-SLNs [（31.71+2.78） μg/（h·cm2）] was significantly higher than that of its raw material [（10.32±3.24） μg/（h·cm2）]， and its lag time [（0.17±0.01） h] was significantly shorter than that of its raw material [（1.57±0.37） h] （P＜0.01）. CONCLUSIONS： Prepared MT-SLNs have small particle size and distributed evenly， and can promote in vitro transcutaneous absorption.

This paper introduces the basic function , composition and framework of the Patient Condition ( PC) codes and the Patient Workload Generator ( PATGEN ) that are used for classification of the wounded and simulation of the patient generation for the U.S.Armed Forces.In addition, chi-square statistics and comparative methods were used for the , analysis of the difference between the simulation data and the real data in Iraq wary .The result of simulation accuracy was tested.Finally, ways to carry out medical service simulation in China were discussed .