ABSTRACT
The field of immunotherapy, particularly immune checkpoint blockade (ICB), holds immense potential in mitigating the progression of cancer. However, the challenges of insufficient tumor antigen production and the immunosuppressive state in the tumor microenvironment substantially impede patients from deriving benefits. In this research, we present a tumor-microenvironment-modulation manganese-based nanosystem, PEG-MnMOF@PTX, aiming to improve the responsiveness of ICB. Under acidic conditions, the released Mn2+ accomplishes multiple objectives. It generates toxic hydroxyl radicals (â¢OH), together with the released paclitaxel (PTX), inducing immunogenic cell death of tumor cells and normalizing tumor blood vessels. Concurrently, it facilitates the in situ generation of oxygen (O2) from hydrogen peroxide (H2O2), ameliorating the microenvironmental immunosuppression and increasing the efficacy of immunotherapy. In addition, this study demonstrates that PEG-MnMOF@PTX can promote the maturation of dendritic cells and augment the infiltration of cytotoxic T lymphocytes through activation of the cyclic guanosine 5'-monophosphate-adenosine 5'-monophosphate synthase (cGAS) and interferon gene stimulator (STING) pathways, namely cGAS-STING pathways, thereby heightening the sensitivity to ICB immunotherapy. The findings of this study present a novel paradigm for the progress in cancer immunotherapy.
ABSTRACT
Cholestatic liver disease is a common liver disease in infants and young children. Liver fibrosis is a key factor affecting the prognosis, and liver transplantation is the only treatment option for liver cirrhosis. This study aimed to explore the efficacy of Combi-elasto for diagnosing liver fibrosis in children affected by cholestatic liver disease. A total of 64 children with S1-S4-grade liver fibrosis were enrolled. The general data, routine ultrasound, Combi-elasto, aspartate aminotransferase-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) score were compared among children with different grades of liver fibrosis, and the efficacy of the above indexes for evaluating the degree of liver fibrosis was reported. There were remarkable differences in liver size, liver echogenicity, Young's modulus (E), fibrosis index (FI), activity index (AI) and FIB-4 score among the groups (all p < 0.05). E and liver echogenicity were the independent impact factors of liver fibrosis. The areas under the curve of E, APRI, FIB-4 score and the combined model (E+ liver echogenicity) in the evaluation of liver fibrosis were 0.84, 0.61, 0.66 and 0.90, respectively. Ultimately, we concluded that CE is an effective method to evaluate liver fibrosis in children with cholestatic liver disease.
