Background and aims As a ferroptosis inducer, sorafenib, a first-line treatment for hepatocellular carcinoma (HCC), has a significant antitumor effect. Nonetheless, HCC patients frequently develop sorafenib resistance. Here, we investigated the impacts of progestagen-associated endometrial protein (PAEP), which controls sorafenib resistance and tumorigenesis in HCC. Furthermore, we investigated the function of PAEP and the underlying molecular mechanisms that cause HCC ferroptosis when sorafenib is applied. Methods Western blot analysis, cell proliferation, colony formation and animal experiments were performed to investigate the function of PAEP in sorafenib resistance and tumorigenesis in HCC. We detected the levels of reactive oxygen species, iron, and malondialdehyde and preformed transmission electron microscopy to investigate the relationship between PAEP and ferroptosis. Co-immunoprecipitation (co-IP) assay was performed to investigate the underlying molecular mechanisms of PAEP that cause HCC ferroptosis. Results PAEP was significantly overexpressed in HCC tissues, and this was associated with a poor clinical prognosis. PAEP silencing dramatically reduced HCC cells’ malignant phenotype. We found that sorafenib-induced ferroptosis was more sensitive to HCC cells with PAEP knockdown. Furthermore, the orthotopic cell line-derived xenograft mouse model results showed that sorafenib sensitivity can be effectively increased in vivo by PAEP knockdown. We determined that transferrin (TF) was a PAEP target using the String database, and we further supported this finding with Co-IP analysis. Additionally, on sorafenib-induced ferroptosis in HCC cells, TF partially reversed the effects of PAEP knockdown. Conclusions Our research indicates that PAEP may be a potential biomarker for predicting sorafenib resistance in HCC and disruption of PAEP expression may be a potential cancer-directed therapeutic option for HCC.

Objective To summarize the practical measures taken by the case hospital to explore the separation mecha-nism of procurement and management,analyze its effectiveness,and provide reference for public hospitals to improve procurement quality.Methods Taking the procurement reform of a tertiary hospital in Jiangsu Province as an example,using the separation of procurement and management as the starting point,a procurement operation mechanism was established at the decision-making level,control level,and execution level,further sorting out the bidding and procurement process,and exploring the practical path of refined management of hospital procurement.Results Through reform practice,the procurement management system has been improved,hospital procurement quality control management has been strengthened,procurement efficiency and budget execution rate have been improved,and anti-corruption risks have been effectively prevented.Conclusion The separation mechanism of procurement and management is a key measure to improve the quality of recruitment and procurement in public hospitals,and can promote refined management in hospitals.

Objective To investigate the Fsp27 gene's influence on the regulation of hepatic stellate cells (HSCs) in vitro.Methods HSCs were isolated from rat liver,the Fsp27 gene was detected in primary HSCs,and activated HSCs were detected by RT-qPCR.After 72 h of Fsp27 transduction through a lentivirus expressing Fsp27 (pLV-Fsp27),the proliferation of HSCs was tested by the CCK-8 test kit,smooth muscle α-actin (α-SMA) expression of HSCs was tested by Western blot,and the fibrosis-related genes were tested by RT-qPCR.Results The HSCs were isolated and cultured successfully,and the Fsp27 genetic difference between primary and activated HSCs was significant (P＜0.01).After coculture for 72 h,Fsp27 inhibited the proliferation and activation of HSCs (P＜0.05).Fsp27 can enhance expression of the MMP-2 gene and down-regulate expression of the TIMP-1 and TGF-β1 gene in activated HSCs (P＜0.05).Conclusion The Fsp27 gene can inhibit the proliferation and activation of HSCs,regulate the expression of fibrosis-related genes,and may play an important role in maintaining the quiescent phenotype of HSCs.

Pulsed electric fields can induce various kinds of biological effects that are essentially different from the normal electric fields, especially the interactions of Nanosecond Pulsed electric field (nsPEF) with cells. The biological effects of different pulsed electric fields on cell membranes, cytoplasmic matrixes, cell growth are introduced in this paper. Based on these effects, some applications of pulsed electric fields in cancer therapy, gene therapy, and delivery of drugs are reviewed in details.
Cell Membrane ; metabolism ; radiation effects ; Cell Physiological Phenomena ; Electromagnetic Fields ; Electrophysiology ; Electroporation ; Genetic Therapy ; methods ; Neoplasms ; therapy

The mechanical properties of tumor cells adhering to extracellular matrix (ECM) are closely related with their invasion and metastesis. In this study we investigated the adhesive mechanical properties between hepatocellular carcinoma cells(HCC) and the collagen I coated surfaces from the viewpoint of cell cycle by coupling cellular biology and cellular mechanics, using micropipette aspiration and cell synchronization technique. The results showed that the synchronous G1 and S phase HCC cells were achieved by use of thymine-2-desoryriboside, colchicines sequential blockage method and double thymine-2-desoryriboside blockage method, and that the synchronous rates of G1 and S phase HCC amounted to 74.09% and 90.39% respectively. Within the ranges of dosing and timing in this study, the adhesion of HCC cells to collagen I displayed dose dependent and time dependent patterns. S phase cells had small force of adhesion to collagen I as compared with G1 phase and controlled cells(P<0.001), which suggested that G1 phase HCC may play an important role in the step of invading interstitial connective tissue in the metastasis pathway of HCC through blood circulation. These are of significance to unveiling the mechanism of HCC metastasis.
Animals ; Cell Adhesion ; Cell Cycle ; Collagen Type I ; metabolism ; Liver Neoplasms, Experimental ; metabolism ; pathology ; Neoplasm Metastasis ; Rats ; Tumor Cells, Cultured