Objective : To identify the main components in the extracts of different parts of Juandan Baihe (Lilium lancifolium) by ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) technology and investigate their hypoglycemic activities. Methods: The MS fragmentation pathways of the main types of compounds in Juandan Baihe (Lilium lancifolium) were studied, and the main components in the extracts were systematically identified using MS fragmentation pathways combined with MS mining technology. Based on the hyperglycemia male mouse model [specific pathogen free (SPF)-grade Kunming mice] induced by streptozotocin (intragastric administration of 80 mg/kg for 3 d), the hypoglycemic effects of extracts of Juandan Baihe (Lilium lancifolium) roots, stems, corms, leaves, and flowers were evaluated by measuring the changes of blood glucose, daily water consumption, daily food intake, and body weight. Result: The MS fragmentation pathways of regalosides, dioscins, phenylpropanoids, flavonoids, and chlorogenic acids in Juandan Baihe (Lilium lancifolium) were clarified, and a mining method for compounds in this plant was constructed. A total of 58 compounds, including 6 chlorogenic acids, 14 regalosides, 13 phenylpropanoids, 5 flavonoids, and 20 dioscins, were identified from the roots, stems, corms, leaves, and flowers of Juandan Baihe (Lilium lancifolium). Among them, 30 compounds were reported for the first time from this plant. The root and corm extracts demonstrated significant hypoglycemic activities by reducing blood glucose levels from 23.76 ± 1.21 and 24.29 ± 1.35 mmol/L to 17.21 ± 1.23 and 18.78 ± 1.49 mmol/L, respectively (P < 0.05). The roots and corms extracts could also attenuate the symptoms of polydipsia (P < 0.01), polyphagia (P < 0.05), and weight loss caused by diabetes. Conclusion This study clarifies that the roots of Juandan Baihe (Lilium lancifolium) are rich in regalosides and dioscins for the first time, and have significant hypoglycemic activities, providing the foundation for the comprehensive utilization of this plant and the development of hypoglycemic drugs.

Radiotherapy (RT) can potentially induce systemic immune responses by initiating immunogenic cell death (ICD) of tumor cells. However, RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases. Herein, we construct multifunctional self-sufficient nanoparticles (MARS) with dual-enzyme activity (GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse. In addition to limiting the Warburg effect to actualize starvation therapy, MARS catalyzes glucose to produce hydrogen peroxide (H₂O₂), which is then used in the Cu⁺-mediated Fenton-like reaction and RT sensitization. RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms, which have a robust ICD impact on mobilizing the immune system. Thus, when MARS is combined with RT, potent systemic antitumor immunity can be generated by activating antigen-presenting cells, promoting dendritic cells maturation, increasing the infiltration of cytotoxic T lymphocytes, and reprogramming the immunosuppressive tumor microenvironment. Furthermore, the synergistic therapy of RT and MARS effectively suppresses local tumor growth, increases mouse longevity, and results in a 90% reduction in lung metastasis and postoperative recurrence. Overall, we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.

Immune checkpoint inhibitors (ICIs) present significant efficacy in the treatment of malignant tumors, and they have been approved as the first-line of treatment for various cancers. Pembrolizumab monotherapy or combined with chemotherapy has been recommended by domestic and foreign guidelines for the first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma. Although ICIs represent a milestone in the treatment of head and neck squamous cell carcinoma, potential problems still need to be addressed, such as the selection of the efficacy predictors for ICIs, the evaluation of the tumor response to ICIs, and the treatment of immune hyperprogression and immune-related adverse events. Therefore, to form a relatively unified understanding of ICIs treatment for head and neck squamous cell carcinoma, we integrated the clinical experience of multi-disciplinary experts of head and neck cancers on the basis of current clinical hot issues and finally developed this consensus.
Humans ; Squamous Cell Carcinoma of Head and Neck/drug therapy* ; Immune Checkpoint Inhibitors ; Consensus ; Neoplasm Recurrence, Local/pathology* ; Head and Neck Neoplasms/drug therapy*