Résumé
As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.
Résumé
Objective:To evaluate the risk factors of mortality in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods:A total of 97 patients with AECOPD in the emergency department of Beijing Friendship Hospital Affiliated to Capital Medical University from January 2018 to January 2019 were prospectively selected and followed up for 2.5 years. According to the prognosis, they were divided into survival group (82 cases) and death group (15 cases). Logistic regression analysis was used to screen the independent risk factors for death. The area under receiver operating characteristic curve (AUC) was used to analyze the prediction accuracy. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to analyze the predictive value of the prediction model for 2.5-year mortality in AECOPD patients.Results:Drinking history ( OR=4.975, P=0.046), past long-term β receptor blockers ( OR=5.486, P=0.029) and creatine kinase isoenzyme (CK-MB) level ( OR=2.008, P=0.049) were independent risk factors for death in patients with AECOPD. The AUC was 0.729, 0.715 and 0.710 respectively. The weight values of the three in the prediction model were 5, 5 and 1 respectively and the AUC was 0.834. Kaplan Meier survival analysis showed that 8 points of the prediction model could predict the 2.5-year survival rate in AECOPD patients (Log Rank P<0.001). The risk of death in AECOPD patients with score >8 was significantly higher than that of patients with score ≤8 ( HR=12.471, 95% CI: 3.735-41.643, P<0.001). Conclusions:Drinking history, past long-term β receptor blockers and CK-MB levels are independent risk factors for 2.5-year mortality in patients with AECOPD. The combination of these three factors has high predictive value for the prognosis of patients.