OBJECTIVE: To explore the effects of different root apex preparation methods on pulp revascularization and periodontal regeneration after autologous tooth transplantation. METHODS: Using 64 anterior teeth from 6 male Bea...OBJECTIVE: To explore the effects of different root apex preparation methods on pulp revascularization and periodontal regeneration after autologous tooth transplantation. METHODS: Using 64 anterior teeth from 6 male Beagle dogs, we compared natural socket preservation (retaining periodontal ligament/PDL) versus artificial socket preparation, with subgroups receiving: (1) circumferential 2 mm apex PDL removal (Cpr), (2) 3 mm apical resection+iRoot BP retrofilling (ArrN/ArrA), (3) apical foramen enlargement >1 mm (Afe), (4) immediate root canal treatment (RCTN/RCTA), or (5) no treatment (ControlA/ControlN). Contralateral autotransplantation of teeth was performed, followed by 6 months of clinical and radiographic monitoring prior to micro-CT and histological analysis. RESULTS: The natural socket group showed superior outcomes, with significantly lower probing depths (P < .05) and better survival rates. Radiographic and Micro-CT revealed severe root resorption in Controls and ArrN groups, while ArrA/Cpr groups exhibited reduced apical radiolucency. Notably, high-density intracanal deposits in ArrN/ArrA suggested pulp regeneration, whereas Afe specimens displayed osteoid-like pulp deposits. Histologically, Controls developed discontinuous PDL (Periodontal ligament), extensive resorption and fibrous tissue thickening, while treated teeth maintained better periodontal integrity. These findings demonstrate that PDL preservation combined with apical sealing (particularly ArrN/ArrA protocols) significantly enhances transplantation success by: (1) maintaining apical vascularity, (2) preventing inflammatory resorption through hermetic sealing, and (3) facilitating stem cell recruitment. CONCLUSION: In tooth autotransplantation, maximal preservation of periodontal ligament cells within the recipient socket helps reduce postoperative root resorption and periodontal inflammation. Sealing the donor tooth apex, whether by intraoperative apical resection-retrofilling or postoperative root canal treatment, effectively controls apical inflammation and improves the success rate of transplantation.
INTRODUCTION AND AIMS: Oral lichen planus (OLP) is a chronic inflammatory disease of unknown etiology. Recent studies have implicated microbial dysbiosis in its pathogenesis. Our previous research revealed an increased a...INTRODUCTION AND AIMS: Oral lichen planus (OLP) is a chronic inflammatory disease of unknown etiology. Recent studies have implicated microbial dysbiosis in its pathogenesis. Our previous research revealed an increased abundance of Fusobacterium nucleatum (F.nucleatum) in OLP tissues, suggesting its potential involvement. METHODS: We utilized single-cell RNA sequencing, spatial transcriptomics, and immunohistochemistry to analyse Claudin-4 expression and its spatial distribution in OLP lesions. In vitro, HaCaT keratinocytes exposed to outer membrane vesicles (OMVs) derived from F.nucleatum (F.n-OMVs) were evaluated for epithelial barrier function via transepithelial electrical resistance (TEER) and fluorescein isothiocyanate-dextran (FD4) permeability assays. Claudin-4 expression and JNK/c-JUN pathway activation were evaluated by qPCR, Western blotting, and RNA sequencing. The JNK inhibitor SP600125 was used to explore pathway involvement. RESULTS: Claudin-4 expression was significantly decreased and exhibited disrupted spatial organization in OLP lesions. F.n-OMVs compromised HaCaT epithelial barrier function, downregulated Claudin-4 expression, and altered its localization. Western blotting demonstrated activation of the JNK/c-JUN signaling pathway. Inhibition of JNK with SP600125 restored Claudin-4 expression and barrier function. CONCLUSION: Our study demonstrates that F.n-OMVs induce epithelial barrier dysfunction in OLP by activating the JNK/c-JUN pathway to downregulate Claudin-4, highlighting a novel microbial mechanism contributing to OLP pathogenesis. CLINICAL RELEVANCE: These findings identify F.n-OMVs as microbial drivers of epithelial barrier disruption in OLP, suggesting that targeting OMVs or the JNK/c-JUN/Claudin-4 axis may offer new diagnostic and therapeutic strategies for OLP management.
AIMS: To evaluate bone regeneration and osseointegration using low-dosage Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2) incorporated with calcium phosphate cement (CPC) via a biomimet...AIMS: To evaluate bone regeneration and osseointegration using low-dosage Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2) incorporated with calcium phosphate cement (CPC) via a biomimetic coating method during simultaneous lateral ridge augmentation with implant placement. MATERIALS AND METHODS: Chronic horizontal alveolar bone defects were created in the mandibles of 5 dogs. Before implant placement, defects were randomly assigned to different grafting groups: autologous bone, CPC, high-dosage ErhBMP-2 (1088 µg/g) adsorbed to CPC (ErhBMP-2 Ads. CPC), and low-dosage ErhBMP-2 (239 µg/g) incorporated with CPC (ErhBMP-2 Inc. CPC). Lateral ridge augmentation was performed at the buccal aspect of each defect during implant surgery. Bone regeneration and contour maintenance were assessed using micro-CT and histology 3 months postoperatively. RESULTS: Micro-CT showed that the ErhBMP-2 Inc. CPC group developed substantial mineralised tissue covering the implant surface, with no exposed threads at the implant neck. Trabecular thickness in this group was significantly greater than in the CPC and autologous bone groups. Histology confirmed greater bone marrow formation and horizontal augmentation below the implant shoulder in the ErhBMP-2 Inc. CPC group compared with CPC alone. Collectively, the histological and radiographic findings were consistent with enhanced peri-implant bone regeneration in the ErhBMP-2 Inc. CPC group. CONCLUSIONS: ErhBMP-2 Inc. CPC enhanced peri-implant bone regeneration than CPC alone. CLINICAL RELEVANCE: Low-dosage ErhBMP-2 incorporated into CPC may offer a more predictable and effective approach for simultaneous lateral ridge augmentation and implant placement by enhancing bone regeneration and maintaining ridge contours.
INTRODUCTION AND AIMS: To develop and validate an AI-automated system for dental charting that accounts for multiple radiograph types and younger patients. METHODS: A total of 3705 dental radiographs were collected in Sl...INTRODUCTION AND AIMS: To develop and validate an AI-automated system for dental charting that accounts for multiple radiograph types and younger patients. METHODS: A total of 3705 dental radiographs were collected in Slovakia and Egypt between 2023 and 2024, including orthopantomograms (OPGs) and intraoral radiographs (e.g. bitewings). Complete teeth were manually annotated with bounding boxes and tooth numbers by 2 calibrated annotators. Subsequently, teeth were assessed by at least 3 trained clinicians (10 total, 2-13 years of clinical experience) for the presence of ten dental findings (caries, crown, filling, implant, pontic, periapical lesion, primary tooth, retained root, root canal treatment, unerupted tooth). Assessments were aggregated using the Dawid-Skene model. The AI system comprised 3 deep learning stages for modality classification (OPG or intraoral radiograph; EfficientNetV2), tooth detection per modality (RTMDet), and dental finding classification (EfficientNetV2) and was evaluated with 5-fold cross-validation on 400 held-out radiographs against the clinicians and 3 independent dentists. RESULTS: Tooth detection was highly effective (F1-score: OPG = 0.99, intraoral = 0.98; tooth number accuracy: OPG = 0.98, intraoral = 0.96) with decreased effectiveness for primary teeth. Dental finding classification saw mixed effectiveness (F1-score: 0.52 to 0.99) with a lower effectiveness for disease-related findings. The system was more accurate than the dentists for caries, crowns, fillings, primary teeth, root canal treatments, and unerupted teeth. CONCLUSION: The AI system outperformed dentists for common findings, but more radiographs and annotations are required to effectively interpret rare conditions. Overall, it can support radiographic diagnosis and speed up dental charting for most patients. CLINICAL RELEVANCE: Interpretation of dental radiographs requires clinical experience and remains challenging. An effective AI system was developed for tooth detection and diagnosis in several types of dental radiographs of young and adult patients. Its findings can enhance the clinical workflow, facilitate dentist-patient communication, and improve diagnostic consistency for prevalent findings.
OBJECTIVES: Tongue squamous cell carcinoma (TSCC) is a highly aggressive malignancy where extracellular matrix (ECM) stiffening drives epithelial-mesenchymal transition (EMT). However, the specific mechanotransduction pa...OBJECTIVES: Tongue squamous cell carcinoma (TSCC) is a highly aggressive malignancy where extracellular matrix (ECM) stiffening drives epithelial-mesenchymal transition (EMT). However, the specific mechanotransduction pathways and the distinction between primary and metastatic cell responses remain insufficiently defined. This study investigated how substrate stiffness regulates TSCC progression via a dual-regulatory mechanism: direct cell-intrinsic mechanotransduction and indirect stromal paracrine signalling. METHODS: Two human TSCC cell lines with distinct origins, HSC-4 (metastatic) and HSC-7 (primary), were cultured on tunable collagen-coated polydimethylsiloxane (PDMS) substrates of varying stiffness (soft and stiff). Cell morphology, migration, proliferation, EMT marker expression, integrin and YAP expressions were assessed using wound healing assays, qRT-PCR and immunofluorescence staining. The involvement of actin cytoskeleton was examined using cytochalasin D. Additionally, the paracrine effects were evaluated by culturing TSCC cells with conditioned media from gingival fibroblasts (HGF-CM) cultured on different substrate stiffness. RESULTS: Stiff substrates induced elongated, mesenchymal-like morphology and significantly enhanced migration in TSCC cells. Increased stiffness also upregulated EMT-associated markers (CDH2, VIM, MMP2), while induced YAP nuclear translocation and increased mechanosensitive integrin expression. Disruption of the actin cytoskeleton with cytochalasin D suppressed this stiffness-induced EMT marker expressions, indicating that cytoskeletal tension mediates mechanotransduction. Furthermore, HGF-CM derived from stiff substrates significantly upregulated EMT-related expression in HSC cells. CONCLUSIONS: Matrix stiffness drives TSCC progression through a dual mechanism: direct actin-mediated and YAP-associated mechanotransduction and indirect stiffness-modulated fibroblast signalling. These findings highlight that mechanical cues in the tumour microenvironment differentially regulate primary and metastatic phenotypes in TSCC. CLINICAL SIGNIFICANCE: Mechanical properties of the tumour microenvironment drive TSCC progression, suggesting that ECM stiffness is likely to be associated with altered TSCC phenotypes, providing a basis for future mechanobiology-focused studies on TSCC progression and management.
INTRODUCTION AND AIMS: Periodontitis is a major cause of tooth loss and a persistent challenge in clinical management. Although both non-surgical periodontal therapy (NSPT) and surgical periodontal therapy (SPT) are wide...INTRODUCTION AND AIMS: Periodontitis is a major cause of tooth loss and a persistent challenge in clinical management. Although both non-surgical periodontal therapy (NSPT) and surgical periodontal therapy (SPT) are widely used for advanced periodontitis (Stages III/IV), their long-term comparative effectiveness in Chinese patients remains not well established. This retrospective study aimed to compare the clinical efficacy of NSPT versus SPT and to identify predictors of long-term treatment success. MATERIALS AND METHODS: This retrospective study included 2982 patients who received NSPT and 212 patients who underwent SPT, all diagnosed with stage III/IV periodontitis. Participants had a baseline periodontal evaluation and at least one re-evaluation between April 2017 and September 2022. Clinical parameters including probing depth (PD), clinical attachment loss (CAL), and bleeding on probing (BOP) were retrieved from a hospital-based electronic periodontal record system. Statistical analyses included independent t-tests, linear regression, and multilevel models, adjusted for age, sex, smoking, and follow-up compliance. RESULTS: Over a mean follow-up of 1.56 years, patients receiving SPT demonstrated significantly greater reductions than NSPT in PD (1.16 ± 1.06 versus 0.77 ± 0.81 mm), CAL (0.97 ± 1.13 versus 0.68 ± 0.90 mm), and BOP% (0.28% ± 0.27% versus 0.23% ± 0.29%) (all P < .01). However, this therapeutic advantage of SPT diminished with longer follow‑up (>3 years). Regular supportive periodontal care was consistently associated with improved clinical outcomes, regardless of whether intervention was SPT or repeated NSPT. CONCLUSIONS: In a large Chinese cohort with advanced periodontitis, SPT provided superior short-term clinical improvements compared to NSPT. However, long-term outcomes depend on sustained maintenance care. These findings highlight that successful periodontal management relies on both patient compliance and clinician awareness of the long-term value of NSPT. CLINICAL RELEVANCE: SPT offers superior short-term outcomes, while NSPT with maintenance achieves comparable long-term stability. Long-term success depends more on maintenance adherence than initial therapy.
INTRODUCTION: This ex vivo study aimed to determine the optimal energy level for virtual monoenergetic imaging (VMI) using photon-counting detector computed tomography (PCD-CT) and to evaluate the effectiveness of iterat...INTRODUCTION: This ex vivo study aimed to determine the optimal energy level for virtual monoenergetic imaging (VMI) using photon-counting detector computed tomography (PCD-CT) and to evaluate the effectiveness of iterative metal artifact reduction (iMAR) in assessing simulated endodontic challenges and complications. METHODS: Sixteen extracted third molars were simulated with one of eight distinct endodontic diagnostic challenges and imaged using PCD-CT at radiation doses equivalent to standard-dose cone-beam CT. VMIs were reconstructed from 70-190 keV at 10 keV increments, both with and without iMAR. Diagnostic accuracy, depiction quality of endodontic challenges, artifact severity, and visualization of key endodontic anatomical structures were independently assessed by 2 observers using a 5-point visual analogue scale (1 = least favourable, 5 = most favourable). Descriptive statistics were calculated, and inter-reader agreement was analysed using Krippendorff's alpha coefficient. RESULTS: VMIs achieved excellent diagnostic accuracy (97%) and high-quality visualization of endodontic challenges (median: 5, IQRs: 4-5 or 4.25-5; α = 0.63-1.00) across the entire reconstructed energy spectrum (70-190 keV), with minimal artifacts, particularly at ≥ 110 keV (α = 1.0). Task-specific analysis demonstrated optimal visualization of caries at 70-80 keV and fractured files at 70-100 keV. For other pathologies, VMI at ≥100 keV effectively reduced artifacts without compromising anatomical detail. IMAR did not improve image quality and consistently reduced diagnostic performance. CONCLUSIONS: VMI from PCD-CT provides high-quality imaging with minimal artifacts, well-suited for indication-specific endodontic diagnostics. CLINICAL RELEVANCE: PCD-CT supports novel, indication-specific workflows in endodontic imaging, potentially enhancing diagnostic precision and long-term treatment follow-up.
OBJECTIVE: To evaluate the clinical efficacy of a dual anchoring technique (DAT) for keratinized tissue width (KTW) augmentation in the posterior mandible, utilising a dual fixation system (orthodontic anchor screws and...OBJECTIVE: To evaluate the clinical efficacy of a dual anchoring technique (DAT) for keratinized tissue width (KTW) augmentation in the posterior mandible, utilising a dual fixation system (orthodontic anchor screws and membrane tacks) to improve soft tissue stability and reduce graft contraction. MATERIALS AND METHODS: This retrospective case series included 25 systemically healthy patients with KTW <2 mm after bone augmentation. Primary outcome was KTW change from baseline (T₀) to 12 months (T₅). Secondary outcomes included graft shrinkage, operative time, complications and postoperative patient-reported outcome measures (PROMs). RESULTS: All 25 patients (49 implant sites) completed the 12-month follow-up. KTW increased from 0.67 ± 0.12 mm (T₀) to 11.00 ± 0.87 mm at 1 month, stabilising at 8.70 ± 0.84 mm at T₅ (net gain: 8.02 ± 0.82 mm; P < .001). Graft shrinkage was 17.48 ± 3.41% at T₅, with 85% occurring within the first 3 months. Mean operative time was 26.40 ± 1.9 min (single-site) and 33.31 ± 2.08 min (2-site). No complications occurred. VAS scores decreased to negligible levels by day 14. CONCLUSION: Within the limitations of this retrospective study, DAT was associated with effective keratinized tissue augmentation in the posterior mandible and favourable dimensional stability over a 12-month period. CLINICAL RELEVANCE: This study introduces DAT designed to reduce the contraction rate of free gingival grafts in the posterior mandible by enhancing their mechanical stability. This technique offers a reliable, practical and a simple surgical protocol for predictable keratinized tissue augmentation in this region.
OBJECTIVE: To evaluate the performance of large language models (LLMs) in responding to oral health consultations and to examine the consistency between the AI-as-a-Judge evaluation framework and human expert ratings. ME...OBJECTIVE: To evaluate the performance of large language models (LLMs) in responding to oral health consultations and to examine the consistency between the AI-as-a-Judge evaluation framework and human expert ratings. METHODS: Nine oral health questions were selected from the World Dental Federation (FDI) official website and posed to 6 models: GPT-5.0, Gemini-3.0, DeepSeek-V3, Qwen3-Max, Kimi-K2 and Doubao-1.8-Pro. Responses were independently scored by 2 clinicians and 3 AI judges. RESULTS: Significant performance differences were observed among the 6 models, with DeepSeek-V3 and Doubao-1.8-Pro achieving the best results. Inter-rater consistency among human experts was good (ICC = 0.860), while consistency among AI judges was low (ICC = 0.538). Human-AI consistency was extremely low (ICC = 0.215) and AI judges exhibited a significantly stricter scoring tendency. CONCLUSION: Leading domestic LLMs have attained competitive performance in oral health consultations. However, the current 'AI-as-a-Judge' framework demonstrates significant inconsistency and bias compared to human experts, suggesting that automated AI evaluation systems are not yet a reliable substitute for human expert review in clinical contexts.
INTRODUCTION AND AIMS: Distant metastasis (DM) in tongue squamous cell carcinoma is associated with poor prognosis. However, reliable tools for immediate postoperative risk prediction remain lacking. This study aimed to...INTRODUCTION AND AIMS: Distant metastasis (DM) in tongue squamous cell carcinoma is associated with poor prognosis. However, reliable tools for immediate postoperative risk prediction remain lacking. This study aimed to develop and validate an interpretable machine learning (ML) model for early risk stratification of DM. METHODS: This study included 752 patients from Sun Yat-sen Memorial Hospital as the model development cohort, while 234 patients from Nanfang Hospital and 105 patients from the HANCOCK database constituted external validation cohorts 1 and 2. Variables were selected using 3 feature selection methods and 6 ML models were developed. Model performance was evaluated using metrics including the area under the receiver operating characteristic curve and interpretability analysis was conducted using Shapley Additive Explanations. RESULTS: A total of 1091 patients were included and 7 key predictors were ultimately identified, including histological grade, lymphovascular invasion, number of regional lymph node metastases, maximum tumour diameter, depth of invasion, neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio. The Elastic Net model demonstrated the best performance, with area under the curves of 0.935 (95% CI 0.882-0.988) in the internal validation cohort, 0.889 (95% CI 0.800-0.978) in external validation cohort 1 and 0.905 (95% CI 0.808-1.000) in external validation cohort 2. The median time to DM was 11.9 months. The model enabled immediate postoperative risk stratification. Shapley Additive Explanations analysis enhanced model interpretability and an online prediction platform was developed for clinical application (https://nfyy-stomatology-dept.shinyapps.io/Predict-DM-of-TSCC/). CONCLUSIONS: This study developed and validated an interpretable ML model using multicentre real-world data for immediate postoperative DM risk stratification. The model provides a reliable and clinically applicable tool to support individualised patient management. CLINICAL RELEVANCE: The model enables immediate postoperative identification of high-risk patients, providing approximately 12 months of earlier risk recognition compared with routine imaging.
OBJECTIVES: Artificial intelligence (AI) is increasingly used for dental radiographic interpretation, yet the effect of image resolution on diagnostic accuracy compared with human evaluators remains unclear. This study e...OBJECTIVES: Artificial intelligence (AI) is increasingly used for dental radiographic interpretation, yet the effect of image resolution on diagnostic accuracy compared with human evaluators remains unclear. This study evaluated how medium- versus high-resolution full-mouth radiographs influence diagnostic performance of an AI system and experienced clinicians. METHODS: In this retrospective comparative study, 200 full-mouth series radiographs were divided equally into medium-resolution (96-300 dpi) and high-resolution (≥720 dpi) groups. Three independent human examiners and an AI system (Diagnocat, San Francisco, CA, USA) assessed six pathological conditions. The reference standard was defined as agreement between at least two human examiners. Diagnostic metrics (sensitivity, specificity, predictive values, accuracy, F1-score) were calculated with 95% confidence intervals. Inter- and intra-examiner reliability and AI-human agreement were assessed using Cohen's kappa. Differences in diagnostic accuracy between resolutions were tested using chi-square tests for independent proportions (or Fisher's exact test where appropriate), with Bonferroni correction for multiple comparisons. RESULTS: Human inter-examiner agreement ranged from moderate to substantial across pathologies (κ = 0.27-0.87), with the highest agreement for missing teeth and the lowest for root resorption. AI-gold standard agreement varied from essentially none to substantial (κ = 0.00-0.90) and increased with higher resolution for most conditions. AI accuracy ranged from 75.3% to 99.1%, with consistently high specificity (73.5%-99.8%) and variable sensitivity (0.0%-93.6%). High-resolution imaging significantly improved AI diagnostic accuracy for caries (+4.3%), furcation involvement (+1.4%), dental calculus (+9.8%), and missing teeth (+3.9%) (all P < .001, after Bonferroni correction), while changes for periapical lesions and root resorption were not significant. CONCLUSIONS: High-resolution radiographs enhance diagnostic accuracy for AI and human evaluators. AI achieved clinically acceptable performance, though sensitivity differed across pathologies. CLINICAL RELEVANCE: High resolution full mouth radiographs improve diagnostic accuracy for both artificial intelligence and human evaluators. This finding underscores the importance of optimal image quality in clinical practice to enhance diagnostic confidence and support AI assisted decision making in dentistry.
INTRODUCTION AND AIMS: Oral lesions are highly prevalent globally, and oral cancer ranks among the most common malignancies, underscoring the need for AI-driven tools to support early detection and triage, especially in...INTRODUCTION AND AIMS: Oral lesions are highly prevalent globally, and oral cancer ranks among the most common malignancies, underscoring the need for AI-driven tools to support early detection and triage, especially in resource-scarce settings. This work investigates the capabilities of multimodal large language models (MLLMs) for automated detection of oral lesions in smartphone-acquired buccal mucosa images. Unlike convolutional neural networks (CNNs), which require large annotated datasets and significant computational resources, MLLMs need no task-specific training and can adapt quickly through intelligent prompting architectures. METHOD: We propose a novel expert-informed mixture-of-experts paradigm that mimics the idealistic collaborative medical decision-making approach of clinicians, where each expert module independently retrieves contextually relevant images and the corresponding expert-generated descriptions from the existing data corpus, guided by different similarity metrics. These enriched examples help the expert to form an independent, informed diagnosis. A specialist MLLM then reviews all expert opinions and the image and synthesises a final decision, effectively emulating a consensus diagnosis process. RESULTS: Experimental results on a dataset of buccal mucosa images show that the proposed method attains a sensitivity of 89.81%, making it comparable with existing CNN-based approaches. Additionally, we provide explainability through a detailed interpretation of experimental results and failure case analysis, supported by insights from medical experts. CONCLUSION: The proposed framework represents a human-AI collaborative model, where we do not leave diagnostic outcomes entirely to the model's internal representations. Rather, it actively shapes the model's reasoning through curated, expert-informed descriptions provided as few-shot examples. Overall, it facilitates reliable decision-making while reducing dependence on large, annotated datasets and extensive computational resources. CLINICAL RELEVANCE: By enabling accurate and interpretable lesion detection from smartphone images, the proposed approach has strong potential to support early triage in low-resource and remote health care environments, contributing to improved oral cancer prevention and patient outcomes.
BACKGROUND: Oral cancer causes approximately 390,000 new cases and 188,000 deaths annually, with substantial functional impairment affecting quality of life. Although dietary associations have been recognised, the nutrit...BACKGROUND: Oral cancer causes approximately 390,000 new cases and 188,000 deaths annually, with substantial functional impairment affecting quality of life. Although dietary associations have been recognised, the nutrition-attributable burden at the population level remains inadequately quantified globally, particularly regarding age-, sex- and region-specific patterns. METHODS: We estimated population attributable fractions (PAFs) for 7 nutritional determinants across 185 countries from 1990 to 2018 using the Global Dietary Database and Global Burden of Disease data. A comparative risk assessment methodology with log-linear dose-response models quantified disease burden attributable to suboptimal dietary intake. Stratified analyses examined sex-specific, age-specific and regional variations. Sensitivity analyses were conducted using relative risk variation analysis, model specification comparison and bootstrap uncertainty analysis. RESULTS: In 2018, fruits (-39.0%), vegetables (-38.8%) and vitamin B9 (-36.5%) exhibited the highest protective PAFs, while sugar-sweetened beverages (+36.1%) demonstrated the greatest harmful impact. The global incidence increased by 56%, despite improvements in protective factors, concurrent with a 37% increase in sugar-sweetened beverage consumption. Males consistently displayed higher PAFs than females across most nutrients (fruits: P = .004; vitamin C: P < .001; processed meats: P < .001), paralleling their 1.9-fold higher global incidence of oral cancer (5.4 vs 2.8 per 100,000). Regional PAF disparities corresponded with cancer-burden patterns: Latin America exhibited the highest sugar-sweetened beverage PAF (+40%) alongside elevated incidence rates (5.5 per 100,000), while South Asia exhibited the greatest vitamin B9 inadequacy (-40%) concurrent with a high regional burden (7.3 per 100,000 in males). Age-gradient analysis revealed that sugar-sweetened beverages disproportionately affected younger age groups (25-29 years: PAF +37.8% vs 75-79 years: PAF +28.9%). However, absolute incidence rates increased with age, reflecting the cumulative nature of cancer risk. Sensitivity analyses confirmed robust estimates (CV: 0.0023-0.0158). CONCLUSIONS: Insufficient intake of fruits (-154.9 g/d), vegetables (-211.9 g/d), vitamin B9 (-449.0 μg/d) and excess sugar-sweetened beverages (+180.1 mL/d) are the predominant modifiable risks. Nonlinear patterns and synergistic interactions suggest the need for multicomponent, region-specific interventions.
AIMS: This review examines the pivotal role of the Notch signalling pathway in the pathogenesis of periodontitis. We focus on its impact on the host inflammatory response, immune regulation, and alveolar bone homeostasis...AIMS: This review examines the pivotal role of the Notch signalling pathway in the pathogenesis of periodontitis. We focus on its impact on the host inflammatory response, immune regulation, and alveolar bone homeostasis. By delineating how periodontal pathogens activate this pathway to exacerbate tissue damage, we also explore its potential as a therapeutic target. METHODS: This article synthesises and critically examines recent advances in research on the Notch signalling pathway in the context of periodontitis. By comprehensively reviewing and evaluating current literature, the methods include analysing mechanistic insights, experimental findings, and clinical evidence related to Notch signalling in periodontal pathogenesis. RESULTS: The review highlights that the Notch signalling pathway significantly influences the pathogenesis of periodontitis, impacting key disease processes such as inflammation, immune response, and tissue regeneration. It summarises evidence demonstrating the pathway's involvement in disease progression and its potential as a therapeutic target, while also identifying existing challenges and gaps in current knowledge. CONCLUSION: This review underscores the critical role of Notch signalling in periodontitis and contributes to a deeper understanding of the molecular mechanisms driving the disease. It encourages the development of novel therapeutic strategies and emphasises the need for further research to address unresolved questions and translate findings into clinical applications.
INTRODUCTION AND AIMS: Periodontitis can cause increases in blood pressure and is a risk factor for poor control of hypertension. Previous studies have found that serum matrix metalloproteinase-9 (MMP-9) is significantly...INTRODUCTION AND AIMS: Periodontitis can cause increases in blood pressure and is a risk factor for poor control of hypertension. Previous studies have found that serum matrix metalloproteinase-9 (MMP-9) is significantly increased in patients with hypertension combined with periodontitis, but it has not been demonstrated whether elevated MMP-9 is related to elevated blood pressure. In this study, we examined whether serum MMP-9 and blood pressure are concomitantly elevated in spontaneously hypertensive rats (SHRs) with periodontitis and explored the potential mechanism. METHODS: Thirty-six 12-week-old male SHRs were randomly divided into an experimental periodontitis group (SHR-L, n = 18) and a nonperiodontitis group (SHR-C, n = 18). Four weeks later, the SHR-C and SHR-L groups were each randomly divided into 3 subgroups and received JNJ0966 (a specific inhibitor of MMP-9) by gavage once per day for 7 days at doses of 0, 10 and 30 mg/kg (n = 6 in each subgroup). Then, the noninvasive caudal artery pressure and serum concentrations of MMP-9, TIMP-1 and Ang II were measured. RESULTS: After 5 weeks of modelling, the MMP-9 levels and the MMP-9/TIMP-1 ratio, the Ang II concentration and the blood pressure measurement were all significantly higher in the SHR-L-0 group than in the SHR-C-0 group (P < 0.05). After intervention with JNJ0966, blood pressure and serum MMP-9 and Ang II levels were significantly lower in the SHR-C-30 group than in the SHR-C-0 group. Compared with those in the SHR-L-0 group, blood pressure, serum MMP-9 levels, the MMP-9/TIMP-1 ratio and Ang II levels were significantly lower in the SHR-L-10 and SHR-L-30 groups (P < 0.05). CONCLUSION: Systemic application of JNJ0966 can significantly reduce the elevated serum MMP-9 and blood pressure observed in SHR with periodontitis. CLINICAL RELEVANCE: This indicates that MMP-9 may be 1 mechanism underlying the increased blood pressure in patients with periodontitis.
INTRODUCTION: The objective of this study was to investigate the effects of parathyroid hormone on tooth movement and uncover its mechanism from a metabolic perspective. METHODS: The influences of parathyroid hormone on...INTRODUCTION: The objective of this study was to investigate the effects of parathyroid hormone on tooth movement and uncover its mechanism from a metabolic perspective. METHODS: The influences of parathyroid hormone on PDLCs osteogenic differentiation and monocyte osteoclastic differentiation were investigated. According to the RNA-seq analysis, glucose metabolism has been discussed subsequently. Mouse maxillary first molar mesial movement model was constructed to estimate the effects of parathyroid administration on alveolar bone remodelling and tooth movement. RESULTS: Parathyroid administration accelerated mouse maxillary first molar mesial movement by promoting alveolar bone remodelling. The expression of osteogenic markers and the number and surface of osteoclast cells were promoted. Parathyroid hormone administration facilitates PDLCs osteogenic differentiation and monocytes osteoclastic differentiation synchronously. RNA-seq indicated that parathyroid administration mainly affects the metabolism and cellular signalling of PDLCs. Parathyroid administration enhanced glucose uptake, glucose consumption and aerobic glycolysis of PDLCs while exhibiting no obvious effects on the Krebs cycle and oxidative phosphorylation. Moreover, mitochondrial fission of PDLCs was promoted after parathyroid administration. Furthermore, results indicated that parathyroid administration promoted the expression of GLUT1, HK1 and LDHA. Inhibition of mitochondrial midzone fission partially alleviated the osteo-inductive effects of parathyroid hormone. CONCLUSIONS: Collectively, parathyroid hormone regulates PDLCs aerobic glycolysis and mitochondrial fission to promote alveolar bone remodelling, and metabolic reprogramming is of vital importance in the processes of orthodontic tooth movement. CLINICAL RELEVANCE: This study elucidates the role of metabolites associated with parathyroid hormones in tooth movement, and lays a foundation for regulating the speed of tooth movement by monitoring their activity.
BACKGROUND: Lip and oral cavity cancer (LOCC) remains a significant issue in Europe, with an uneven public health burden. While trends have shifted, regional and sex-specific disparities persist due to modifiable risk fa...BACKGROUND: Lip and oral cavity cancer (LOCC) remains a significant issue in Europe, with an uneven public health burden. While trends have shifted, regional and sex-specific disparities persist due to modifiable risk factors. Using Global Burden of Disease 1990 to 2023 estimates, this study evaluates long-term trends and projects Europe's future LOCC burden. METHODS: The Global Burden of Disease (GBD) Study data of 2023 were examined to evaluate the trends of incidence, prevalence, and mortality of LOCC in Central, Eastern, and Western Europe. We conducted a retrospective analysis of age-standardized incidence (ASIR), prevalence (ASPR), and mortality rates (ASMR), alongside disability-adjusted life years (ASDR). Trends over time were examined using Joinpoint regression to estimate average Annual Percent Change (AAPC:). Furthermore, ARIMA time-series models were employed to generate future burden for the period 2024 to 2033. RESULTS: From 1990 to 2023, Europe showed a clear East-West divide in LOCC. Western Europe successfully lowered its death rates (AAPC: -1.08%) and disability rates (AAPC: -1.41%). However, Central and Eastern Europe saw new cases rise (AAPC: 0.63% and 0.60%) along with more alcohol-related deaths. The highest burden was in Russia and Hungary, where male DALYs rate reached 207 per 100,000. ARIMA forecasting shows this gap will grow by 2033; while Central Europe's ASIR is expected to fall to 4.65 per 100,000, Eastern Europe's prevalence is projected to rise to 18.12 per 100,000 population. CONCLUSION: Europe highlights widening variations in LOCC burden, with Western Europe achieving substantial progress while Central and Eastern Europe face continuous worsening trends.
OBJECTIVES: By establishing a rat model of periapical infection, this study compared the anti‑inflammatory effects of caerin 1.1/1.9 hydrogel and calcium hydroxide paste, aiming to provide a novel therapeutic strategy fo...OBJECTIVES: By establishing a rat model of periapical infection, this study compared the anti‑inflammatory effects of caerin 1.1/1.9 hydrogel and calcium hydroxide paste, aiming to provide a novel therapeutic strategy for refractory apical periodontitis. METHODS: Forty-five male Sprague-Dawley rats were randomly divided: caerin 1.1/1.9 (F1/F3) peptide containing gel group (F1/F3, n = 15), calcium hydroxide group (CH, n = 15) and untreated control group (UC, n = 15). The F1/F3 group and CH group animals received an intracanal application of 5 mg/mL F1/F3-loaded hydrogel or calcium hydroxide paste, respectively, into the ipsilateral mandibular first molar immediately (day 0) and subsequently at 7 and 14 days post apical-foramen enlargement. At the 7th, 14th and 21st days after the operation, the degree of infection was comprehensively evaluated through periapical X-ray films, HE staining, immunohistochemical staining, enzyme histochemical staining and ELISA tests. RESULTS: At the 7th and 14th day after operation, the expression of IL-17 and the contents of TNF-α and IL-6 in F1/F3 and CH groups were significantly lower than those in UC group. On the 21st day after the operation, the number of osteoclasts in F1/F3 and CH groups decreased and the expression of OPG increased and the difference was statistically significant (P < .05). Compared with the CH group, the number of TNF-α and osteoclasts in F1/F3 group was significantly decreased on the 14th and 21st day after the operation and the expression of OPG was increased and the expression of IL-6 and IL-17 was decreased on the 21st day after the operation in F1/F3 group (P < .05). CONCLUSIONS: The F1/F3 gel showed a more positive trend in regulating the key inflammatory factors and bone immune indicators related to periapical periodontitis compared to the calcium hydroxide paste.