Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

Microwave thermochemotherapy (MTC) has been applied to treat lip squamous cell carcinoma (LSCC), but a deeper understanding of its therapeutic mechanisms and molecular biology is needed. To address this, we used single-cell transcriptomics (scRNA-seq) and spatial transcriptomics (ST) to highlight the pivotal role of tumor-associated neutrophils (TANs) among tumor-infiltrating immune cells and their therapeutic response to MTC. MNDA⁺ TANs with anti-tumor activity (N1-phenotype) are found to be abundantly infiltrated by MTC with benefit of increased blood perfusion, and these TANs are characterized by enhanced cytotoxicity, ameliorated hypoxia, and upregulated IL1B, activating T&NK cells and fibroblasts via IL1B-IL1R. In this highly anti-tumor immunogenic and hypoxia-reversed microenvironment under MTC, fibroblasts accumulated in the tumor front (TF) can recruit N1-TANs via CXCL2-CXCR2 and clear N2-TANs (pro-tumor phenotype) via CXCL12-CXCR4, which results in the aggregation of N1-TANs and extracellular matrix (ECM) deposition. In addition, we construct an N1-TANs marker, MX2, which positively correlates with better prognosis in LSCC patients, and employ deep learning techniques to predict expression of MX2 from hematoxylin-eosin (H&E)-stained images so as to conveniently guide decision making in clinical practice. Collectively, our findings demonstrate that the N1-TANs/fibroblasts defense wall formed in response to MTC effectively combat LSCC.
Humans ; Neutrophils/metabolism* ; Single-Cell Analysis ; Lip Neoplasms/genetics* ; Hyperthermia, Induced/methods* ; Microwaves/therapeutic use* ; Transcriptome ; Carcinoma, Squamous Cell/immunology* ; Tumor Microenvironment

Objective To investigate the feasibility of amplitude of intraoperative nerve action potentials (NAP) for early quantitative diagnosis of peripheral nerve injury. Methods The sciatic nerve injury model were established in 16 rabbits. Intraoperative NAP were recorded after 4 weeks. According to amplitude of NAP, the injuried nerve were divided into 3 groups: NAP ＜ 100 μV in A group, 100 μV ≤NAP ＜ 500 μV in B group, NAP ≥ 500 μV in C group. Nerve specimen 1cm distal to injuried point were resected that received glycine silver stain and image analysis including number, diameter and cross section area of regenerative axons. Footprint parameter and ulcer area were measured and contrasted between each two groups. Results The number, diameter and cross section area of A group regenerative axons have significant difference with B and C group, no significant difference between B and C group; Footprint parameter and ulcer area have significant difference in each two groups. Conclusion Amplitude of intraoperative NAP can be a quantitative criteria to diagnose the degree of peripheral nerve injury that provides experiment evidence for guide intraoperative decision-making in clinical practice.

Objective To observe the efficacy of WS-frequency spectrum in treating second degree burn wounds. Methods 350 cases of second degree burn were treated in the whole couse with WS-frequency spectrum in association with systemic treatment including anti-shock,anti-infection and expecant treatment. Results All the patiens healed,only 23 cases with deep burn area over 20% TBSA resulted in superficial pigmentation and scar formation without dysfuntion. Conclusion WS-frequency spectrum is a good remedy for treating second degree burn. This method is easy and simple to apply and has very good efficacy.