Objective To explore a novel and highly specific small-molecule TNFβinhibitor by using computer-aid?ed virtual screening and cell-based assays in vitro. Methods Computer-aided drug design and virtual screening were used to design and identify chemical compounds that targeted TNFβbased on the crystal structure of the TNFβ-TNFR1 com?plex. The effect of the small-molecule compound against TNFβ-induced cytotoxicity of L929 cells was detected by MTT as?say, and the efficacy of the compound to inhibit TNFβ-induced apoptosis of L929 cells was determined by flow cytometry as?say. The impact of the compound on L929 cell cycle was examined by Propidium Iodide (PI) staining and flow cytometry, and the influence of the compound on TNFβ-triggered signal pathway was analyzed by Western blot assay and Ultra VIEW VOX 3D Live Cell Imaging System. Results No.35 compound (named as C35 thereafter) could effectively inhibit TNFβ-induced cell death in a dose dependent manner, and the half-maximum inhibition concentration (IC50) was 8.19μmol/L. Furthermore, C35 had lower cytotoxicity and minimal effect on L929 proliferation. Here we further revealed that C35 could affect TNFβ-induced apoptotic pathway by blocking the activation of Caspase 3, and markedly reduce L929 cell apoptosis induced by TNFβ. Conclusion A novel TNFβsmall-molecule inhibitor was identified by combining computer-aided virtual screening with functional assays, and which could block TNFβ-triggered apoptotic pathway and efficiently inhibit the cell death in?duced by TNFβ.

Objective To investigate the effects of cleaning and disinfection of thermoplastic masks on the hospital infection in patients receiving precise radiotherapy for nasopharyngeal carcinoma ( NPC). Methods A prospective study was performed among 102 patients receiving precise radiotherapy for NPC from 2013 and 2016, consisting of 18 patients with early?stage ( I, Ⅱ) disease and 84 patients with advanced (Ⅲ, IV) disease. All patients were randomly divided into group A and group B using a random number table. For group A, the marker lines of thermoplastic masks were sandwiched by double plastic tapes;cleaning and disinfection plus ultraviolet ( UV ) disinfection were applied to the masks 1 h prior to radiotherapy and immediately after radiotherapy. For group B, only conventional UV disinfection was applied to the masks. The surface of the masks was examined and hospital infection during radiotherapy was evaluated. Results At the 18th radiotherapy, group A had a significantly lower mask surface colony count than group B (7.90±650 vs. 139.05±12929 CFU/cm2, P=0000). Group A also had a significantly lower incidence of hospital infection than group B (725% vs. 882%, P=0046). For the patients with early stage NPC, particularly, there was no significant difference in the incidence of infection between the two groups (556% vs. 667%, P=0629). For patients with advanced NPC, group A had a significantly lower incidence of infection than group B ( 762% vs. 929%, P=0035) . There were no significant differences in incidence rates of oral mucosal, skin, and respiratory system infections between the two groups ( 471% vs. 510%, P=0692;176% vs. 235%, P=0463;78% vs. 137%, P=0338) . In both groups A and B, the incidence of oral mucosal infection was significantly higher than the incidence rates of skin infection ( P=0001, 0000) and respiratory system infection ( P=0004, 0000) . Conclusions Thermoplastic mask is one of the risk factors for hospital infection in patients receiving precise radiotherapy for NPC. Timely cleaning and disinfection plus UV disinfection can significantly reduce the surface colony count and the incidence of hospital infection in patients with NPC, particularly in those with advanced NPC receiving precise radiotherapy. The incidence of hospital infection is the highest in the oral mucosa, followed by the skin and the respiratory system.

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