Prophylactic central lymph node dissection need be considered in PTMC patients presenting with risk factors. In PTMC patients with a solitary primary tumor, tumor location can assist in the evaluation of LLNM. We recommend multicenter research and long-term follow-up to better understand the risk factors and surgical management of PTMC.
Among approaches of current cancer immunotherapy, a dendritic cell (DC)-targeted vaccine based on nanotechnology could be a promising way to efficiently induce potent immune responses. To enhance DC targeting and vaccine efficiency, we included imiquimod (IMQ), a toll-like receptor 7/8 (TLR 7/8) agonist, and monophosphoryl lipid A (MPLA), a TLR4 agonist, to synthesize lipid-polymer hybrid nanoparticles using PCL−PEG-PCL and DOTAP (IMNPs) as well as DSPE-PEG-mannose (MAN-IMNPS). The spatiotemporal delivery of MPLA (within the outer lipid layer) to extracellular TLR4 and IMQ (in the hydrophobic core of NPs) to intracellular TLR7/8 can activate DCs synergistically to improve vaccine efficacy. Ovalbumin (OVA) as a model antigen was readily absorbed by positively charged DOTAP and showed a quick release in vitro. Our results demonstrated that this novel nanovaccine enhanced cellular uptake, cytokine production, and maturation of DCs. Compared with the quick metabolism of free OVA-agonists, the depot effect of OVA-IMNPs was observed, whereas MAN-OVA-IMNPs promoted trafficking to secondary lymphoid organs. After immunization with a subcutaneous injection, the nanovaccine, especially MAN-OVA-IMNPs, induced more antigen-specific CD8 + T cells, greater lymphocyte activation, stronger cross-presentation, and more generation of memory T cells, antibody, IFN-γ, and granzyme B. Prophylactic vaccination of MAN-OVA-IMNPs significantly delayed tumor development and prolonged the survival in mice. The therapeutic tumor challenge indicated that MAN-OVA-IMNPs prohibited tumor progression more efficiently than other formulations, and the combination with an immune checkpoint blockade further enhanced antitumor effects. Hence, the DC-targeted vaccine codelivery with IMQ and MPLA adjuvants by hybrid cationic nanoparticles in a spatiotemporal manner is a promising multifunctional antigen delivery system in cancer immunotherapy.
The mammalian peptide hormone stanniocalcin 2 (STC2) plays an oncogenic role in many human cancers. However, the exact function of STC2 in human head and neck squamous cell carcinoma (HNSCC) is unclear. We aimed to examine the function and clinical significance of STC2 in HNSCC. Using in vitro and in vivo assays, we show that overexpression of STC2 suppressed cell apoptosis, promoted cell proliferation, migration, invasion, and cell cycle arrest at the G1/S transition. By contrast, silencing of STC2 inhibited these activities. We further show that STC2 upregulated the phosphorylation of AKT and enhanced HNSCC metastasis via Snail-mediated increase of vimentin and decrease of E-cadherin. These responses were blocked by silencing of STC2/Snail expression or inhibition of pAKT activity. Furthermore, clinical data indicate that high STC2 expression was associated with high levels of pAKT and Snail in tumor samples from HNSCC patients with regional lymph node metastasis (P < 0.01). Thus, we conclude that STC2 controls HNSCC metastasis via the PI3K/AKT/Snail signaling axis and that targeted therapy against STC2 may be a novel strategy to effectively treat patients with metastatic HNSCC.
Objectives: This study aimed to observe the efficacy of corticosteroids in non-severe COVID-19 pneumonia. Methods: A retrospective study based on propensity score matching was designed to explore the effects of corticosteroids. Primary outcomes included the rate of patients who developed severe disease and mortality. Secondary outcomes included duration of fever, virus clearance time, length of hospital stay, and the use of antibiotics. Results: A total of 475 patients with non-severe COVID-19 pneumonia were enrolled, 55 patients received early, low-dose, and shortterm corticosteroids therapy, 420 patients received non-corticosteroids therapy. Compared to the non-corticosteroids group, there was a prolonged duration of fever (median 5 vs 3 days, p \ 0.001), virus clearance time (median 18 vs 11 days, p \ 0.001), and length of hospital stay (median 23 vs 15 days, p \ 0.001) in the corticosteroids group. The percentages of antibiotics therapy (89.1% vs 23.6%, p \ 0.001), use of at least two antibiotics (38.2% vs 12.7%, p = 0.002), and antifungal therapy (7.3% vs 0, p = 0.042) were higher in the corticosteroids group than those in the non-corticosteroids group. Compared to the non-corticosteroids group, more patients developed severe disease (12.7% vs 1.8%, p = 0.028) in the corticosteroids group. There was no significant difference between the two groups in mortality (1.8% vs 0, p = 0.315). Conclusion: In adult patients with non-severe COVID-19 pneumonia, early, low-dose, and short-term corticosteroids therapy was associated with worse clinical outcomes.
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