With the increasing proportion of human papilloma virus (HPV) infection in the pathogenic factors of oropharyngeal cancer, a series of changes have occurred in the surgical treatment. While the treatment mode has been improved, there are still many problems, including the inconsistency between diagnosis and treatment modes, the lack of popularization of reconstruction technology, the imperfect post-treatment rehabilitation system, and the lack of effective preventive measures. Especially in terms of treatment mode for early oropharyngeal cancer, there is no unified conclusion whether it is surgery alone or radiotherapy alone, and whether robotic minimally invasive surgery has better functional protection than radiotherapy. For advanced oropharyngeal cancer, there is greater controversy over the treatment mode. It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy, or a treatment mode of surgery combined with postoperative chemoradiotherapy. In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer, this expert consensus, based on the characteristics and treatment status of oropharyngeal cancer in China and combined with the international latest theories and practices, forms consensus opinions in multiple aspects of preoperative evaluation, surgical indication determination, primary tumor resection, neck lymph node dissection, postoperative defect repair, postoperative complication management prognosis and follow-up of oropharyngeal cancer patients. The key points include: ① Before the treatment of oropharyngeal cancer, the expression of P16 protein should be detected to clarify HPV status; ② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resection of oropharyngeal cancer. Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction; ③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months, it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment; ④ Early-stage oropharyngeal cancer patients may opt for either surgery alone or radiation therapy alone. For intermediate and advanced stages, HPV-related oropharyngeal cancer generally prioritizes radiation therapy, with concurrent chemotherapy considered based on tumor staging. Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma (including primary and recurrent) and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy; ⑤ For primary exogenous T1-2 oropharyngeal cancer, direct surgery through the oral approach or da Vinci robotic surgery is preferred. For T3-4 patients with advanced oropharyngeal cancer, it is recommended to use temporary mandibulectomy approach and lateral pharyngotomy approach for surgery as appropriate; ⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth >3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients, selective neck dissection of levels IB to IV is recommended. For cN+ HPV unrelated oropharyngeal cancer patients, therapeutic neck dissection in regions I-V is advised; ⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node, or imaging suggests continuous enlargement of lymph nodes, the patient should undergo neck dissection; ⑧ For patients with suspected extracapsular invasion preoperatively, lymph node dissection should include removal of surrounding muscle and adipose connective tissue; ⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps, with priority given to adjacent flaps, followed by distal pedicled flaps, and finally free flaps. The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.
Objective To explore whether the environmental pollutant triclosan (TCS) has negative effects on the various biological characteristics of dental pulp stem cells (DPSCs), as well as the distribution and hazards of TCS in rat dental pulp tissue in vivo, which will provide a basis for the clinical application of DPSCs and the safety of TCS. Methods Tooth collection was approved by the Ethics Committee of Tianyou Hospital Affiliated to Wuhan University of Science and Technology. Human DPSCs were extracted, cultured, and identified. Up to 0.08 mmol/L of TCS was added to the in vitro culture medium of DPSCs. The proliferation ability of DPSCs was detected by CCK-8. The migration ability of DPSCs was detected via scratch assay. The differentiation ability of DPSCs was detected by inducing trilineage differentiation. The gene or protein expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), inducible nitric oxide synthase (iNOS), and transforming growth factor-β (TGF-β) in DPSCs were detected. The level of reactive oxygen species (ROS) generated by DPSCs was analyzed using fluorescence staining. Changes in mitochondrial membrane potential of DPSCs were detected using a fluorescent probe. The activity of PI3K/Akt/mTOR, p38, and JNK pathways of DPSCs were detected. Animal experiments were approved by the Animal Ethics Committee of Wuhan University of Science and Technology. A rat model of short-term oral exposure to 50 mg/kg/d of TCS for 2 months was established, and the TCS concentration in the liver, brain, and dental pulp tissues of rats was detected through liquid chromatography-mass spectrometry. Results TCS at 0.02 mmol/L, 0.04 mmol/L, and 0.08 mmol/L significantly inhibited the proliferation ability of human-derived DPSCs on the 5th and 7th days of contact. TCS at 0.04 mmol/L and 0.08 mmol/L significantly inhibited the migration ability and tri-lineage differentiation ability of DPSCs on the 3rd day of contact. TCS induced the gene or protein expression of proinflammatory factors including TNF-α, IL-1β, IL-6, and iNOS, induced the gene or protein expression of TGF-β, and inhibited the protein expression of anti-inflammatory factor IL-10. On day 1, TCS at 0.04 mmol/L and 0.08 mmol/L induced the production of ROS in DPSCs and reduced the mitochondrial membrane potential of DPSCs. On day 3, TCS at these levels inhibited PI3K/Akt/mTOR pathway activity and enhanced p38 pathway activity of DPSCs, without affecting the pathway activity of JNK. After short-term intragastric exposure of rats to TCS, TCS was detected in liver (430 ng/mL) and brain (41.4 ng/mL) tissues but not in the dental pulp. The TCS concentration was highest in the liver, but no obvious histopathological changes were observed. Conclusion TCS inhibits a variety of biological characteristics of DPSCs and poses a potential risk to the organism. No TCS exists in the dental pulp tissue of rats exposed to TCS for a brief period of time, and the health of the rats is not damaged.
Objective To investigate the effect of resveratrol (RSV) in the treatment of peri-implantitis in a murine model and its effect on nuclear factor kappa-B (NF-κB) signaling and mitogen-activated protein kinase (MAPKs) signaling. Methods This study has been reviewed and approved by the Ethics. After extracting the right maxillary molars of 40 C57BL/6 mice and allowing them to heal naturally for 8 weeks, implants were implanted at the site of the first molar. The mice were randomly divided into a control group, a mouse peri implantitis model group, a low-dose group of 20 mg/kg resveratrol (RSV-L), and a high-dose group of 40 mg/kg resveratrol (RSV-H). After 4 weeks of implant implantation, a silk thread ligation induced peri implantitis model was established in all mice except for the control group. The model group received intervention with physiological saline by gavage, while the drug group received intervention with resveratrol by gavage for 6 consecutive weeks. After 6-week treatment, observe the swelling of the gums around the implant and measure the bone resorption around the mouse implant using micro CT. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in gingival crevicular fluid. HE staining was used to observe the infiltration of inflammatory cells in the surrounding tissues of mouse implants. Protein expression level and phosphorylation level of extracellular regulated protein kinases (ERK), p-ERK, c-Jun N-terminal kinase (JNK), p-JNK, p38 mitogen activated protein kinase (p38 MAPK), p-p38MAPK, nuclear factor kappa-B (NF-κB), p-NF-κB, nuclear factor-κB inhibitory protein (IκΒα), p-IκBα in MAPKs/NF-κB signaling pathway were detected by Western blot (WB). Results Resveratrol group showed reduced tissue edema and decreased alveolar bone resorption. Among them, the high-dose resveratrol group had lighter tissue edema and weaker bone resorption compared to the low-dose group. The micro CT results showed that significant changes in the bone level around the implant were observed in the model group mice at four sites: proximal, distal, buccal, and palatal. High dose resveratrol intervention reduced alveolar bone resorption (P<0.05); compared with the low-dose group, the high-dose group showed a decrease in palatal bone resorption (P<0.05), while there was no significant difference in absorption between the mesial, distal, and buccal sides (P>0.05). The ELISA results showed that compared with the model group, the levels of TNF - α and IL-6 in the gingival crevicular fluid of mice in the low-dose and high-dose resveratrol groups were lower (P<0.05). The IL-6 in the gingival crevicular fluid of mice in the high-dose resveratrol group was lower than that in the low-dose group (P<0.05). However, there was no significant difference in TNF-α levels between the two groups. HE staining showed a decrease in inflammatory cell infiltration in mice after treatment with resveratrol. The WB results showed that compared with the control group, the expression levels of p-Erk, p-JNK, p-p38MAPK, p-IκA, and p-NF-κB phosphorylated proteins in the gingival tissue of the model group mice were significantly increased (P<0.01). The resveratrol treatment group significantly inhibited the phosphorylation of p-Erk, p-JNK, p-p38MAPK, p-IκA, and p-NF-κB proteins. Compared with the low-dose group, the high-dose group inhibited the phosphorylation of MAPKs/NF-κB signaling pathway related proteins more significantly (P<0.05). Conclusion Resveratrol protect ligature induced peri-implantitis murine model, which may be related to its inhibition of phosphorylation of MAPKs/NF-κB pathway.
Objective To investigate the expression and role of the DNA repair and recombination protein RAD54-like (RAD54L) in oral squamous cell carcinoma (OSCC). Methods Using OSCC-related data from The Cancer Genome Atlas (TCGA) database, the difference in RAD54L expression between OSCC and control samples was analysed using the Mann-Whitney rank sum test, and the potential value of RAD54L mRNA in OSCC diagnosis was assessed using the receiver operator characteristic curve. The correlation between RAD54L expression levels and clinicopathological data of OSCC patients was analysed using the chi-square test. Once OSCC samples were divided into two groups of high and low expression based on the median value of RAD54L mRNA expression, Cox regression analysis was used to compare the prognostic differences between the two groups. The differentially expressed genes between the groups were subsequently screened using the DESeq2 package, and KEGG pathway enrichment analysis was performed using the clusterProfiler package. The correlation between RAD54L mRNA and gene expression in the homologous recombination repair pathway was demonstrated by Spearman correlation analysis. After clarifying the bioinformatics significance of RAD54L, RAD54L knockdown experiments were performed in human oral squamous carcinoma cell line HSC-3, and the knockdown efficiency was verified through real-time quantitative polymerase chain reaction. After transfection, the changes in proliferation, migration, apoptosis, and cycle of HSC-3 cells were assessed by CCK-8, 5-ethynyl-2'-deoxyuridine (EdU) staining, wound healing, apoptosis, and cell cycle assays. Results Bioinformatics analysis showed that the expression of RAD54L mRNA was higher in OSCC than in normal controls (P<0.001) and had a high value in predicting poor prognosis (AUC = 0.927). The high RAD54L expression group was associated with an increased proportion of male patients (P = 0.032), having a higher T-stage (P = 0.040), clinical stage (P = 0.027), and pathological grading (P = 0.013). Once OSCC samples were divided into two groups of high and low expression using the median value of RAD54L mRNA expression, the prognosis of the group with high expression of RAD54L was poorer than that of the group with low expression (P = 0.049). The differentially expressed genes between the high and low RAD54L expression groups two groups were mainly enriched in neuroactive ligand-receptor interactions, cytokine-cytokine receptor interactions, calcium signaling pathway, cell cycle, gastric cancer, extracellular matrix receptor interactions, chemical carcinogenesis-DNA adducts, DNA replication, homologous recombination, and mismatch repair pathways (P<0.05). In the homologous recombination repair pathway, the expression of RAD54L was positively correlated with the expression of BRCA1, BLM, EME1, XRCC2, POLD1, TOPBP1, RAD51, BRIP1, RAD54B, BRCA2, and SYCP3 (P<0.05), and was strongly positively correlated with the expression of BRCA1, BLM, and EME1 (R>0.8, P<0.05). The results of in vitro experiments showed that RAD54L expression was knocked down to approximately 25% in HSC-3 cells (P<0.001). Compared with the control group, the RAD54L knockdown group showed a lower proliferation rate (P<0.05), a lower proportion of EdU-positive cells (P<0.001), a lower proportion of wound closure (P<0.001), a higher proportion of G1-phase cells (P<0.001), a lower proportion of S-phase cells (P<0.001), and a higher proportion of apoptotic cells (P<0.001). Conclusion RAD54L is highly expressed in OSCC and correlates with poor prognosis. Down-regulation of RAD54L expression inhibits the proliferation and migration of HSC-3 cells, promotes apoptosis, and impedes cell cycle progression.
Objective To explore the characteristics and correlation of the chin and airway in females with skeletal Class Ⅱ mandibular retraction for reference for clinical diagnosis and therapy. Methods This study was approved by the hospital Medical Ethics Committee. Forty cases of skeletal Class Ⅱ mandibular retraction adult females with average angle were selected as the research group, and sixty cases of skeletal Class Ⅰ patients with average angle were selected as the control group. Cone-beam computed tomography (CBCT) images for all subjects were analyzed using three-dimensional modeling software. Measurements included the chin morphology, position, and upper airway morphology. Results Compared with skeletal Class I patients, patients with skeletal Class Ⅱ mandibular retraction had smaller anterior chin thickness, base bone volume, chin total volume, and larger chin angle, chin depression, chin curvature, and alveolar area with statistically significant differences (P<0.05). Gn-V, Gn-H, Po-NB distance, and facial angle were smaller, and the Y-axis angle was larger in patients with skeletal Class Ⅱ mandibular retraction with statistically significant differences (P<0.05). Upper airway total volume, transverse and sagittal diameter of the glossopharynx upper boundary were smaller in patients with skeletal Class Ⅱ mandibular retraction with statistically significant differences (P<0.05). The correlation analysis between the morphology and position of the chin and the morphology of the upper airway in patients with Class Ⅱ mandibular retraction showed that there was a negative correlation between chin angle and laryngopharynx length in patients with Class Ⅱ mandibular retraction (r = -0.277, P<0.01). There was a negative correlation between Po-NB distance and palatopharyngeal length (r = -0.222, P<0.05). Chin height (r = -0.261, P<0.01) and basal bone area (r = -0.225, P<0.05) were negatively correlated with the transverse diameter of the palatopharyngeal upper boundary. The minimum chin thickness (r = 0.245, P<0.05), chin angle (r = 0.249, P<0.05), and alveolar area (r = 0.213, P<0.05) were positively correlated with the sagittal diameter of the palatopharyngeal upper boundary. Gn-V (r = 0.217, P<0.05) and Po-NB distance (r = 0.208, P<0.05) were positively correlated with the transverse diameter of the glossopharynx upper boundary. Anterior chin thickness was negatively correlated with the sagittal diameter of the laryngopharynx upper boundary (r = -0.211, P<0.05). Chin depression was negatively correlated with the sagittal diameter of the laryngopharynx lower boundary (r = -0.237, P<0.05). Chin curvature was positively correlated with the transverse diameter of the laryngopharynx lower boundary (r = 0.231, P<0.05). Conclusion Patients with skeletal Class Ⅱ mandibular retraction exhibit thinner chins. The sagittal position of the chin is backward, and the vertical position is upward. Patients with skeletal Class Ⅱ mandibular retraction have a narrow glossopharyngeal airway. There is a correlation between the morphology and position of the chin and the morphology of the upper airway in patients with Class Ⅱ mandibular retraction.
Objective To explore the effect of a phased rehabilitation training programme to relieve shoulder dysfunction in patients after neck dissection and to provide effective solutions for postoperative shoulder joint function recovery of patients. Methods This study has been reviewed and approved by the Ethics Committee, and informed consent has been obtained from patients. A phased rehabilitaiton training programme for the shoulder after neck dessection was developed through literature review and discussion, and 70 eligible patients from Hospital of Stomatology, Sun Yat-sen University from December 2020 to April 2021 were selected and randomly divided into the test group and control group (35 patients in each group). The control group underwent motor rehabilitation training from 6 weeks postoperative to 1 year after surgery, such as shoulder mobility and coordination training and small range of motion training of the neck, while the test group took part in a rehabilitation training program that included familiarization maneuver training, protective rehabilitation, exercise rehabilitation, and resistance training in the following four stages: preoperative, postoperative general anesthesia and awake until the removal of stitches, the removal of stitches until 6 weeks after surgery, and 6 weeks after surgery until 1 year after surgery. The frequency of training in both groups was at least 3 days per week, and the length of each training session was 10-15 min. The intensity of exercise was 2-3 points on the Borg Conscious Exercise Intensity Scale (i.e., mild-to-moderate tachypnea or fatigue). The neck dissection injury index (NDII) was used to evaluate the quality of life related to shoulder joint function at four time points: preoperative, postoperative 3 months, postoperative 6 months, and postoperative 12 months. The higher the score, the better the quality of life. Results 28 cases in the test group and 32 cases in the control group completed a one-year follow-up. At 3 and 6 months postoperative, the NDII of the test group was significantly higher than that of the control group [3 months postoperative: test group (93.48 ± 9.36) vs. control group (80.00 ± 11.34) (P<0.001), 6 months postoperative: test group (98.21 ± 4.76) vs. control group (90.70 ± 9.12) (P<0.001)]; 12 months after surgery, the NDII of the test group (97.23 ± 4.88) was still higher than that of the control group (96.33 ± 4.49), but the difference was not statistically significant (P = 0.458). The difference in NDII scores among subjects at 3, 6, and 12 months after surgery was statistically significant in each group (P<0.001). Conclusion The application of the phased rehabilitation training method in neck dissection patients has a feasibility and could improve the quality of life of patients' shoulder joint function within 6 months after surgery.
Antimicrobial photodynamic therapy uses photosensitizers to produce reactive oxygen species under light exposure to inhibit pathogenic bacteria. Although its application in the management of oral infectious diseases has increased over recent years, it is limited by inadequate tissue and biofilm penetration and suboptimal bioavailability exhibited by individual photosensitizers. These challenges can potentially be surmounted through the integration of nanomaterials, such as polymers, metals and metal oxides, metal-organic frameworks, and carbon and silicon nanomaterials. Polymers allow the controlled release of photosensitizers through structural adjustments but have low stability, while metals and metal oxides possess strong antibacterial properties but can be potentially toxic. Meanwhile, metal-organic frameworks have flexible structures and multifunctionality but have low stability and potential toxicity. Moreover, carbon and silicon nanomaterials, despite exhibiting excellent antibacterial properties and biocompatibility, have limited application due to high production costs. Materials with inherent antibacterial properties, such as chitosan and graphene oxide, have broader application prospects, as they can form multimodal antibacterial platforms with photosensitizers, enhancing the antibacterial effects and eliminating infections. Future research could incorporate other functional materials, such as anti-inflammatory agents and immunomodulatory materials, to construct comprehensive therapeutic nanoplatforms for the treatment of oral infectious diseases.
The irreversible destruction of periodontal tissue caused by periodontitis is the result of an imbalance between external pathogenic factors and the internal immune response. As human immune cells, macrophages have both pro- and anti-inflammatory roles in the occurrence and development of periodontitis. Pathogenic bacteria, inflammatory cytokines, and neutrophils in the periodontal microenvironment can significantly affect the metabolism and functional status of macrophages, and the status of macrophages can regulate disease processes. By activating the NF-κB signaling pathway, the bacteria cause macrophages to undergo M1 proinflammatory polarization and pyroptosis, forming a microenvironment that induces periodontal tissue destruction. With the development of the disease, numerous apoptotic neutrophils are recognized and phagocytized by macrophages (i.e. efferocytosis), which can both inhibit the NF-κB pathway and activate the nuclear receptors PPAR and LXR, promoting the anti-inflammatory polarization of M2 and further enhancing the efferocytosis activity of macrophages. As a result, these treatments can limit tissue inflammatory damage and promote tissue repair. In recent years, periodontitis treatment strategies focusing on macrophage regulation have received extensive attention, including gene knockout, nanoparticles, exosomes, miRNA, and polyunsaturated fatty acid diets. In this article, we review the specific role of macrophages in periodontitis from three aspects, including macrophage polarization, pyroptosis, and efferocytosis, which may improve our understanding of periodontitis and provide possible directions for periodontitis treatment strategies.
Neutrophil extracellular traps (NETs) are fibrous web-like structures composed of decondensed chromatin and granular proteins released by neutrophils, with the ability to capture and kill bacteria. Pathogens, such as bacteria and viruses, can trigger the formation of NETs via NETosis, a type of programmed cell death that has two distinct forms: suicidal NETosis and vital NETosis. Numerous studies have found that NETs interact with immune cells in the tumor microenvironment, where they activate macrophages, promote immunosuppressive effects of myeloid-derived suppressor cells, and coat the tumor surface to prevent cytotoxic effects of CD8+ T cells and natural killer cells. Recent research has identified a substantial presence of NETs in oral squamous cell carcinoma (OSCC) tissues, indicating a complex relationship between NETs and OSCC development. Depending on the phenotype of neutrophils, NETs may exhibit pro-tumor or anti-tumor effects. For instance, NETs derived from N1-type neutrophils may exert anti-tumor effects, while TGF-β-induced NETs derived from N2-type neutrophils may exert pro-carcinogenic activity, thereby contributing to the development of oral squamous metaplasia. Furthermore, NETs likely play a role in OSCC metastasis by capturing circulating tumor cells and inducing a hypercoagulable state, thereby facilitating tumor-related thrombus formation and hematogenous metastasis. The involvement of NETs in the occurrence and progression of OSCC opens new avenues for anti-tumor therapy and prognostication. Inhibiting NET formation can significantly suppress the development of chemotherapy-induced drug resistance and reduce the risk of thrombosis in OSCC patients, thereby inhibiting tumor metastasis. Currently, multiple prognostic models based on NET-related genes have been constructed and validated for head and neck squamous cell carcinoma, indicating the potential clinical value of NETs. However, the association between NETs and OSCC treatment is still unclear, necessitating further research on its underlying mechanisms and feasibility. This article attempts to review the relationship between NETs and OSCC, aiming to provide novel perspectives for OSCC treatment.
MXenese is a type of two-dimensional inorganic compound in materials science that is composed of transition metal carbides, nitrides, or carbonitrides with several atomic layer thicknesses. Owing to the presence of hydroxyl groups or terminal oxygen groups on the surface of MXene materials, they exhibit metallic conductivity similar to that of transition metal carbides. Owing to their excellent optical, mechanical, electrothermal, and biocompatible properties, emerging 2D MXenes are widely used in biomedical fields such as tissue engineering, antimicrobial drugs, photothermal therapy, drug/gene delivery, sensing, and regenerative medicine. In this paper, we review the methods for synthesizing and modifying MXene-based composites, their research and application in stomatology, and their development prospects and challenges in the clinical application of tissue engineering. The biocompatibility and osteogenic properties of MXene and its nanocomposites have the potential to promote cell proliferation and bone regeneration. The anti-bacterial adhesion and biofilm formation properties can be applied to implant coating and prevent caries. The excellent photothermal, conductive, and mechanical sensitivity of this agent make it suitable for drug delivery, bio-photothermal therapy, immune signal sensing, and gene detection. On this basis, MXene has recently achieved outstanding results in the fields of stomatology, including bone tissue engineering, antimicrobial, drug delivery, physical and mechanical enhancement of dental biomaterials, oral cancer treatment, and periodontal disease monitoring. However, research on the prevention and treatment of refractory oral diseases has not yet been reported. At present, the properties and surface modification of MXene-based nanomaterials are relatively well understood. Future studies should focus on the dose-dependent biosafety, cellular and molecular mechanisms, and signaling pathways of MXene to fully exploit its unique advantages in oral clinical and tissue engineering fields.
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