The homeostasis of the oral microbiome is essential for maintaining host health, and its disruption can contribute to the development of both oral and systemic diseases. The oral microbiome influences the initiation and progression of oral squamous cell carcinoma (OSCC) through multiple mechanisms. ① Oral microbes can directly act on epithelial cells, inducing cell-cycle dysregulation, DNA damage, and epigenetic reprogramming, thereby promoting cell proliferation and epithelial-mesenchymal transition (EMT). For example, Fusobacterium nucleatum binds to E-cadherin via its adhesin FadA, activating the β-catenin pathway and directly driving tumor-cell proliferation and EMT, while Porphyromonas gingivalis reprograms lipid synthesis to enhance the stemness of OSCC cells. ② Oral microbes and their metabolites reshape the tumor immune-suppressive microenvironment by altering the density, composition, and function of infiltrating immune cells. Periodontal pathogens induce a chronic inflammatory state in the oral cavity and activate signaling cascades such as MAPK/ERK and NF-κB, thereby indirectly accelerating OSCC progression. ③ Bacteria and viruses in the oral cavity exhibit synergistic interactions. Bacterial biofilms and proteases facilitate viral activation and infection, and microbial metabolites such as butyrate can enhance histone acetylation to promote the lytic reactivation of latent viruses. ④ At the ecological level, the depletion of commensals and expansion of anaerobic pathogens disrupt the metabolic network of the community, and complex interspecies interactions collectively shape a pro-carcinogenic niche that drives OSCC progression on multiple fronts. Future studies should integrate multi-omics analyses with longitudinal clinical cohorts to explore functional causal networks of key microbial communities and develop individualized targeted intervention strategies for microecology.

According to the differences in function and structure, the nasal cavity can be roughly divided into three regions:the vestibule, respiratory zone, and olfactory zone. The current mainstream of research believes that the process of drugs entering the brain through the nasal cavity mainly occurs in the latter two regions, with the olfactory zone being the primary area. To allow more effective ingredients to enter the brain or reach the above-mentioned delivery pathway targets quickly, when developing related drug products, it should be possible to deliver the drug to the upper nasal cavity, like the upper respiratory zone and olfactory zone. Therefore, special drug delivery devices that can target the upper nasal cavity play a key and core role in Nose-to-Brain delivery. It is nasal spray device Nose-to-Brain delivery products approved by FDA mainly use. The following are three main research directions of the Nose-to-Brain delivery devices. 1) In-depth assessment and research of critical quality attributes and their influencing factors. Many research institutions and enterprises have conducted extensive research on liquid or powder sprays aided by nasal spray devices, and it is currently agreed that spray pattern, plume geometry, and particle size are the critical quality attributes, which can be mainly affected by spray devices and content properties. A spray with a smaller angle can penetrate the nasal valve easier and deliver to the upper nasal cavity. 2) The study of delivery platforms for such complex drug-device combinations is also a key direction, such as Exhalation Delivery Systems (EDS), Precision Olfactory Delivery Systems (POD®), and Controlled Particle Dispersion Technology (CPD) platforms, etc., which are general technology platforms established by drug delivery device manufacturers to better achieve Nose-to-Brain delivery. They have indeed achieved more accurate drug delivery, more significant therapeutic effects, and more convenient use for patients. 3) Combining drug delivery devices with new technologies. For example, adding mucosal adsorbents and permeation enhancers to the prescription, and preparing medicinal products using nanoparticle formulation technology. It is new directions for future research and development which can further meet the needs of Nose-to-Brain delivery. Nose-to-Brain delivery bring new hope to a wide range of clinical needs for brain diseases due to its special advantages. In order to play the truly important role of Nose-to-Brain delivery, it is not only the industry make efforts in research and industrialization, but also regulatory aspects need scientific evaluation and reasonable regulation of emerging technologies. Here are our thoughts. First, we need to pay attention to the important role of regulatory science in the technical research and evaluation of Nose-to-Brain delivery products. Next, we need to pay attention to the interaction and collaboration between scientific researchers, industry, regulators, and users. Then, regulatory authorities needs to broaden its thinking flexibility and attach importance to the role of individual drug guidelines, summary key technical points and solutions from multiple cases. Finally, we need to pay attention to the design, research and development support, and industrialization security of domestic drug delivery devices.