Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

Exploration of the underlying mechanisms of tumor occurrence and development,as well as evaluation of the efficacy of anticancer drug treatments,relies on various research models both in vivo and in vitro.Over the past few decades,with the rapid advancement of biomedical technology,significant achievements have been made in this field.Gene detection technology has progressed from a single-gene perspective to multi-gene approaches,resulting in rapid de-velopment of bioinformatics and transformation of the conceptual understanding of malignant tumors.Moreover,in vitro cell research models have evolved from monolayer two-dimensional and primary cultures to three-dimensional configura-tions,which better imitate the cellular interactions and functions within tumor tissues.Furthermore,in vivo animal re-search models have transitioned from traditional carcinogen induction and cell or tissue xenografts to genetically engi-neered animal models or xenograft models,enabling targeted investigation into the roles of relevant genes in the occur-rence and development of tumors.Clinical research has shifted from simple retrospective to prospective studies,includ-ing phase Ⅰ/Ⅱ/Ⅲ clinical trials,investigator-initiated clinical trials,and real-world clinical trials.The major shortcom-ings of current malignant tumor research models include their singularity,insufficient simulation of the tumor microenvi-ronment,disparities between animal models and human tumors,and the lack of consideration for personalized medicine.Further research and optimization of the models are still needed in the future,along with more effective integration of different models to form an optimized comprehensive experimental model system.This review systematically examines and comprehensively overviews the evolution of malignant tumor research models with the aim of providing more refer-ences to researchers engaged in oncology research.

Free tissue flap transplantation is the preferred option for repairing and reconstructing postoperative defects in oral and maxillofacial-head malignant tumors. However, challenges remain for oral and maxillofacial-head and neck oncology surgeons in terms of ischemia-reperfusion (I/R) injury, airway management, quality of life and prognosis. I/R injury is an inevitable complication of free-flap transplantation surgery. In addition to shortening the vascular anastomosis time as much as possible during the surgical process, many studies have attempted to further prevent and treat free-flap I/R injury using physical intervention therapy, antioxidant and reactive oxygen species (ROS) scavenger therapy, hyperbaric oxygen therapy, etc. However, there is a lack of large-scale clinical randomized controlled trial evidence to further support these methods. Postoperative tracheal management of patients receiving free tissue flap transplantation is very important. In recent years, delayed extubation has been proposed as an alternative to traditional tracheostomy. This method can facilitate wound care for patients, reduce infections, speed up patient recovery, and reduce the incidence of vascular crises. In the future, such management is expected to improve the practicality and safety of delayed extubation by formulating more appropriate patient selection criteria and intensive care plans. Preoperative selection of suitable free tissue flaps according to the defect for repair and reconstruction is beneficial for improving the quality of life and survival rate of patients. At the same time, for patients who require postoperative radiotherapy, reducing the complications of postoperative radiotherapy and improving the quality of life of patients can be achieved through intraoperative nerve anastomosis, preradiation oral hygiene maintenance, early speech training, and other methods.

The heterogeneity of exhausted T cells (Tex) is a critical determinant of immune checkpoint blockade therapy efficacy. However, few studies have explored exhausted T cell subpopulations in human cancers. In the present study, we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer (HNSCC) by multiplex immunohistochemistry (mIHC) to investigate two subsets of Tex, CD8⁺PD1⁺TCF1⁺ progenitor exhausted T cells (TCF1⁺Tex^prog) and CD8⁺PD1⁺TCF1^- terminally exhausted T cells (TCF1^-Tex^term). Moreover, fresh tumor samples from 34 patients with HNSCC were examined by flow cytometry and immunohistochemistry to further investigate their properties and cytotoxic capabilities and their correlation with regulatory T cells (Tregs) in the tumor immune microenvironment (TIME). mIHC and flow cytometry analysis showed that TCF1^-Tex^term represented a greater proportion of CD8⁺PD1⁺Tex than TCF1⁺Tex^prog in most patients. TCF1⁺Tex^prog produced abundant TNFα, while TCF1^-Tex^term expressed higher levels of CD103, TIM-3, CTLA-4, and TIGIT. TCF1^-Tex^term exhibited a polyfunctional TNFα⁺GZMB⁺IFNγ⁺ phenotype; and were associated with better overall survival and recurrence-free survival. The results also indicated that larger proportions of TCF1^-Tex^term were accompanied by an increase in the proportion of Tregs. Therefore, it was concluded that TCF1^-Tex^term was the major CD8⁺PD1⁺Tex subset in the HNSCC TIME and that these cells favor patient survival. A high proportion of TCF1^-Tex^term was associated with greater Treg abundance.
CD8-Positive T-Lymphocytes ; Head and Neck Neoplasms/therapy* ; Humans ; Immunotherapy/methods* ; Prognosis ; Programmed Cell Death 1 Receptor ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Tumor Microenvironment ; Tumor Necrosis Factor-alpha

The evaluation of immune function plays an important role in the diagnosis, treatment and prognosis of many diseases. To date, immune function detection includes cellular immunity, humoral immunity, and inflammatory markers. In this paper, the application of immune function detection in the diagnosis, differential diagnosis and treatment monitoring of various diseases was discussed; then, the application value of immune function detection in the diagnosis and treatment of three common oral mucosa-related diseases, including recurrent aphthous ulcer (RAU), oral lichen planus (OLP), and oral squamous cell carcinoma (OSCC), were reviewed combined with the literature and our research. Our research found that RAU patients present abnormal humoral immune function and obvious inflammatory reactions, whereas OLP and OSCC patients present mild inflammatory reactions and more serious abnormal cellular and humoral immune function, so the combined detection of immune function has a certain guiding value for the diagnosis and treatment of these diseases. Moreover, in the future, it is necessary to carry out a study on large sample, multicenter and multiindex joint detection to better clarify the role of immune dysfunction in the pathogenesis of various diseases and its mechanism, to establish the corresponding diagnostic model and prognostic prediction model, to find more effective treatment methods.

Benign condylar hyperplasia is one of the causes of mandibular lateral deformity, it is easily to be misdiagnosed clinically and leads to the treatment failure. This article will elaborate the etiology and clinical features of benign condylar hyperplasia, as well as the diagnostic points and treatment progress, based on the literature and the clinical experience of our research group, to provide evidence-based medical evidence for the standardized clinical treatment of benign condylar hyperplasia. The etiology of benign condylar hypertrophy includes neurotrophic disorders, local circulatory disorders, traumatic injuries (especially condylar injuries that occur in childhood), unilateral mastication, temporomandibular arthritis, endocrine disorders, condylar osteoma, and heredity. Benign condylar hypertrophy is insidious, and occurs most frequently in individuals 10-30 years old, and the course of disease can last for many years. Its clinical characteristics are slow progressive facial asymmetry. Radionuclide bone scans have become the basis for the diagnosis and differential diagnosis of and treatment planning for benign condylar hypertrophy. Different treatment plans for active and inactive periods need to be developed, including close observation, proportional condylar resection and orthognathic surgery.

In recent decades, although great progress has been made on the diagnosis and treatment of oral squamous cell carcinoma (OSCC), its 5-year survival rate has not been significantly improved. The basic reason is the unclear pathogenesis, lack of effective molecular markers for assessing invasion, metastasis, and recurrence as well as therapeutic targets. The present view is that genetic and epigenetic abnormalities are related to the occurrence and development of OSCC. Epigenetic inheritance is a biological behavior that can be regulated and reversed, and it plays an important role in the occurrence and development of malignant tumors. First, this review will describe the role of epigenetic modifications in the development of OSCC in combination with our research and the latest research progress of epigenetics, including DNA methylation, RNA methylation, short noncoding RNAs (miRNAs, etc.), long noncoding RNAs, circular RNAs, histone modifications (acetylation and methylation), chromatin remodeling and genomic imprinting. Then, we will analyze the value of epigenetic studies in the prevention, diagnosis, and targeted therapy of OSCC.

Epidemiological studies have shown that abnormal glucose and lipid metabolism is associated with a variety of malignant tumors, including oral squamous cell carcinoma. In this paper, the role of abnormal glucose and lipid metabolism, especially diabetes mellitus and obesity, in the occurrence and development of oral squamous cell carcinoma and its pathogenesis are reviewed based on the research results of our group and the literature. Hyperglycemia and insulinemia in diabetes mellitus are the main mechanisms that increase the risk of cancer. Our research shows that hyperglycemia can promote the proliferation, invasion and metastasis of tongue squamous cell carcinoma through the glycolytic enzyme M2 pyruvate kinase (PKM2) and hexokinase 2 (HK2). Hyperinsulinemia can promote the proliferation, invasion and metastasis of tongue squamous cell carcinoma by activating the insulin-like growth factor signal transduction system. Obese patients are often accompanied by increased serum adipokine Chemerin (Chem). Our study shows that serum Chem concentrations in obese patients with tongue cancer are significantly higher compared with nonobese patients. Chem can regulate the proliferation, invasion and migration of tongue squamous cell carcinoma cells through the SOD2-H2O2 signaling pathway. These results provide a basis for the prevention of oral squamous cell carcinoma, provide a new iqdea for the precise treatment of oral squamous cell carcinoma, and suggest that the treatment of oral squamous cell carcinoma should also actively treat patients with diabetes and obesity.

PURPOSE: Several signaling pathways have been shown to regulate the lineage commitment and terminal differentiation of bone marrow stromal cells (BMSCs). Bone morphogenetic protein (BMP) signaling has important effects on the process of skeletogenesis. In the present study, we tested the role of bone morphogenetic protein receptor (BMPR) in the osteogenic differentiation of rat bone marrow stromal cells in osteogenic medium (OM) with or without BMP-2. MATERIALS AND METHODS: BMSCs were harvested from rats and cultured in OM containing dexamethasone, beta-glycerophosphate, and ascorbic acid, with or without BMP-2 in order to induce osteogenic differentiation. The alkaline phosphatase (ALP) activity assay and von kossa staining were used to assess the osteogenic differentiation of the BMSCs. BMPR mRNA expression was assessed using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The BMSCs that underwent osteogenic differentiation in OM showed a higher level of ALP activity and matrix mineralization. BMP-2 alone induced a low level of ALP activity and matrix mineralization in BMSCs, but enhanced the osteogenic differentiation of BMSCs when combined with OM. The OM significantly induced the expression of type IA receptor of BMPR (BMPRIA) and type II receptor of BMPR (BMPRII) in BMSCs after three days of stimulation, while BMP-2 significantly induced BMPRIA and BMPRII in BMSCs after nine or six days of stimulation, respectively. CONCLUSION: BMSCs commit to osteoblastic differentiation in OM, which is enhanced by BMP-2. In addition, BMP signaling through BMPRIA and BMPRII regulates the osteogenic differentiation of rat BMSCs in OM with or without BMP-2.
Alkaline Phosphatase/metabolism ; Animals ; Bone Marrow Cells/*cytology/drug effects/*metabolism ; Bone Morphogenetic Protein 2/pharmacology ; Bone Morphogenetic Protein Receptors/genetics/*metabolism ; *Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Cells, Cultured ; Culture Media/pharmacology ; Male ; Osteogenesis/drug effects/genetics ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Stromal Cells/*cytology/drug effects/*metabolism