Research Progress of Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma / 中国肺癌杂志

Malignant pleural mesothelioma (MPM) is a malignant tumor with strong invasiveness, low survival rate and lack of effective treatment options. As the only first-line treatment plan for the advanced MPM, combination of pemetrexed and cisplatin chemotherapy have been existing since the last 20 years. Immunotherapy has long been considered as a potential treatment plan for MPM, mainly including immune checkpoint inhibitors (ICIs), immunotoxin therapy, anti-cancer vaccine and adoptive T-cell therapy. This review focuses on summarizing the current research status of immune checkpoint inhibitors in MPM, discusses the effect of tumor heterogeneity on ICIs treatment, and describes that the biomarker-oriented immunotherapy is a new vision for the realization of individualized treatment of MPM.
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Effect of clemastine fumarate on TLR4/PI3K/Akt signaling pathway during hypoxia-reoxygenation in rat cardiomyocytes / 中华麻醉学杂志

Objective To evaluate the effect of clemastine fumarate on Toll-like receptor 4/phosphatidylinositol-3-kinase/serine-threonine kinase (TLR4/PI3K/Akt) signaling pathway during hypoxia-reoxygenation (H/R) in rat cardiomyocytes.Methods H9C2 cells of rats cultured in vitro were seeded in culture wells or dishes at a density of 1×105 cells/ml and divided into 3 groups (n=11 each) by using a random number table method:control group (group C),H/R group and clemastine fumarate group (CF group).Cardiomyocytes were exposed to 5％ CO2-95％ N2in a low-glucose DMEM medium at 37℃ for 4 h followed by 4 h reoxygenation.At 4 h of reoxygenation,the cell viability was detected by CCK-8 assay,the ultrastructure was observed with a transmission electron microscope,the expression of TLR4,PI3K,phosphorylated Akt (p-Akt) and caspase-3 was detected by Western blot,and the expression of TLR4,PI3K and caspase-3 was detected by immunofluorescence.Results Compared with group C,the cell viability was significantly decreased,the expression of TLR4 and caspase-3 was up-regulated,and the expression of PI3K and p-Akt was down-regulated in group H/R (P＜0.05).Compared with group H/R,the cell viability was significantly increased,the expression of TLR4 and caspase-3 was down-regulated,the expression of PI3K and p-Akt was up-regulated (P＜0.05),and the mitochondrial damage was significantly attenuated in group CF.Conclusion The mechanism by which clemastine fumarate alleviates H/R injury to rat cardiomyocytes may be related to inhibiting TLR4 expression and activating PI3K/Akt signaling pathway.