Immune checkpoint inhibitors (ICIs) and sonodynamic therapy (SDT) are types of immunotherapy. In order to combine soluble programmed cell death protein 1 (sPD-1)mediated immune checkpoint therapy and chlorin e6 (Ce6)-assisted SDT, nanobubbles (NBs) were generated to simultaneously load sPD-1 and Ce6. Materials and Methods: The sPD-1/Ce6-NBs, which were prepared by thin-film hydration and mechanical oscillation, had a stable physical condition, and delivered sPD-1 and Ce6 in a targeted manner. NBs could strengthen tumor suppression by increasing tumor-targeting accumulation of Ce6 and sPD-1, and by inducing ultrasound-targeted NB destruction. A mouse H22 cell hepatoma xenograft model was used to evaluate the synergetic immunotherapeutic effect and mechanism of sPD-1/Ce6-NBs. Results: By observing the tumor inhibition rate, tissue and cell apoptosis, apoptosis-related genes and protein expression, the best immunotherapeutic effect was exhibited by the sPD-1/ Ce6-NBs group. The immunotherapeutic mechanism initially demonstrated that when tumor cells were transfected by sPD-1 delivered by NBs, which downregulated the expression of programmed death-ligand 1 (PD-L1) in tumor cells, and blocked the PD-1/PD-L1 signaling pathway, which improved T-cell-mediated tumor inhibition. Furthermore, ICIs combined with SDT induced immunogenic cell death by translocating calreticulin to the cell surface and then synergistically enhancing antitumor immune responses.
Conclusion:In conclusion, sPD-1/Ce6-NBs were successfully designed. Ultrasoundmediated sPD-1/Ce6-NBs are potentially effective delivery systems for combination immunotherapy of hepatocellular carcinoma.
Background:
Endoscopic ultrasound (EUS) fine-needle biopsy (FNB) has become an efficient method for diagnosing gastrointestinal (GI) subepithelial lesions (SELs). However, recent guidelines have not regarded FNB as the primary strategy for diagnosing GI SELs. We performed this study to systematically measure the efficacy, feasibility, and safety of EUS-FNB in diagnosing GI SELs.
Materials and Methods:
Relevant studies were searched in PubMed and EMBASE and published after January 2015 were included. The overall rates of diagnostic yield, technical success, and adverse events were calculated as outcome measures. The Jadad scale and the Newcastle-Ottawa scale were used to evaluate the quality of the trials, funnel plots and Egger’s test were used to measure publication bias, and sensitivity and subgroup analyses were performed to explore the variance of heterogeneity and sensitivity, respectively.
Results:
Sixteen studies analyzing 969 patients between 2015 and 2020 were included. Studies showed little change in sensitivity, and 13 were considered high quality. A certain degree of publication bias existed in the diagnostic accuracy rate. The overall rates of diagnostic yield, technical success, and adverse events were [85.69% (95% confidence interval (CI): 82.73-88.22, I
2=41.8%), 98.83% (95% CI: 96.73-99.97, I
2=54.3%), and 1.26% (95% CI: 0.35-2.54, I
2=0.0%)]. No clinical influencing factors were identified in the subgroup analysis.
Conclusions:
EUS-FNB is a promising technology with a relatively superior diagnostic yield, technical success, and security, which is an optimal option for the diagnosis of SELs.
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