This case report describes the nonsurgical management of a retreatment patient using a hemisection-based space closure technique in a 25-year-old woman with convex profile, dental irregularities, missing maxillary second premolars, impacted mandibular third molars, and severely compromised mandibular first molars with alveolar bone resorption and apical periodontitis. The treatment approach featured mandibular first-molar hemisection combined with controlled orthodontic space closure to achieve simultaneous dental alignment and periodontal regeneration. Facial profile enhancement was accomplished through maxillary arch distalization while preserving arch form and dental health. The controlled mesial movement of mandibular second molars during space closure facilitated guided alveolar bone reconstruction, transforming the previously compromised periodontal sites into healthy, functional areas. The favorable results achieved in this case indicate that mandibular first-molar hemisection with phased space closure represents a viable treatment approach for guiding alveolar bone reconstruction and promoting periodontal regeneration in similar complex orthodontic cases.
Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH), which contributes to systemic metabolic disorders. However, the mechanisms underlying CIH-induced intestinal dysfunction remain unclear. In this study, we investigated the effects of CIH on intestinal barrier integrity, gut microbiota, and host metabolism using a multi-omics approach. Male C57BL/6J mice were exposed to six weeks of CIH or normoxia. Colonic barrier integrity was assessed by histological and molecular analyses. Gut microbiota was profiled by full-length 16S rRNA gene sequencing. Untargeted metabolomics was performed on fecal and serum samples, followed by integrated microbiome-metabolome analysis. CIH markedly impaired colonic barrier integrity, as evidenced by disrupted crypt architecture, reduced goblet cell abundance, and decreased expression of ZO-1, Occludin, and Claudin-5. CIH also induced gut microbial dysbiosis, characterized by depletion of the beneficial mucin-associated bacterium Akkermansia muciniphila and enrichment of several anaerobic taxa. Metabolomic analysis revealed opposite alterations of PC (20:2/0:0) and LysoPE (20:5/0:0) between feces and serum, whereas melatonin was consistently decreased in both compartments. Integrated multi-omics analysis further revealed close associations between microbial dysbiosis and metabolic remodeling. Collectively, these findings demonstrate that CIH disrupts intestinal homeostasis through coordinated alterations in barrier integrity, gut microbiota composition, and host metabolism, providing new insights into the intestinal mechanisms underlying OSA-associated systemic dysfunction.
Background/Objectives: Pediatric obstructive sleep apnea (OSA), particularly when accompanied by mandibular retrognathia, presents as a complex, multifactorial condition. Dentofacial orthopedic treatment (DOT) has gained increasing clinical attention; however, high-level evidence specifically demonstrating its efficacy in pediatric OSA remains scarce. This study aimed to evaluate the efficacy of DOT and AT in managing mild to moderate OSA in children with mandibular retrognathia. Methods: This open-label, randomized controlled clinical trial recruited 93 children aged 7-10 years with mild to moderate OSA (an AHI of 1-10 events per hour) and mandibular retrognathia (ANB angle ≥ 4.5°). Participants were randomly allocated to four groups: pharmacotherapy, DOT (combined maxillary expansion and mandibular advancement appliance), AT (adenotonsillectomy under general anesthesia), and AT & DOT groups. The primary outcome was the change in apnea-hypopnea index (AHI) from baseline to 7 months post-treatment. Secondary outcomes included assessments of dentofacial development and volumetric changes in the upper airway. Results: Because of the high dropout/loss-to-follow-up rates in the pharmacotherapy and AT plus DOT groups, the final analysis was restricted to the DOT and AT groups, in which the overall dropout/loss-to-follow-up rate was 19.6%. Among the 43 participants allocated to the DOT (8 girls and 15 boys) and AT groups (8 girls and 12 boys), 36 completed the follow-up, the median baseline AHI was 3.7 events/h [IQR, 1.9-4.4]. Per protocol analysis revealed a mean reduction in AHI of 1.6 events/h in the DOT group and 1.3 events/h in the AT group, with no significant difference between the groups (-0.43 [95% CI, -1.48 to 0.61], p = 0.40). DOT significantly promoted sagittal mandibular growth without inducing a vertical clockwise rotation tendency, whereas AT had no significant effect on dentofacial development. Total upper airway volume increased significantly in both groups, with the increase concentrated in different regions of the upper airway depending on the group. Conclusions: In children with mild to moderate OSA and mandibular retrognathia, DOT demonstrated comparable efficacy to AT, which may be attributable to favorable anatomical remodeling of the upper airway.
Cognitive impairment is a growing global health challenge, yet its multifactorial drivers remain incompletely understood. Intermittent hypoxia (IH) and periodontitis are identified as significant independent risk factors that frequently co-occur. This study investigates the mechanisms through which these conditions accelerate cognitive decline. Here, utilizing a comorbid mouse model, we demonstrate that outer membrane vesicles (OMVs) derived from Porphyromonas gingivalis exacerbate IH-induced mitochondrial oxidative stress and neuroinflammation, leading to neuronal damage and mitochondrial dysfunction in the hippocampus. Specifically, this process is driven by the activation of the HIF-1α/HMGB1/NLRP3 signaling axis. To target this pathology, an asymmetric RVG-Au&mSiO2-TPP-VB Janus nanoformulation is developed for hierarchical neuron-to-mitochondria targeting. The inherent asymmetry of the Au&mSiO2 Janus architecture enables anisotropic, spatially segregated functionalization of its two distinct domains. The neuron-targeting RVG peptide and the mitochondria-targeting ligand TPP are anchored on distinct domains, while vitamin B2 (VB) is encapsulated within the mesopores. Intranasal administration of this nanoformulation achieves precise mitochondrial accumulation in neurons, effectively scavenging reactive oxygen species, suppressing neuroinflammation, and significantly restoring cognitive function. Our findings reveal a molecular pathway through which IH and periodontitis jointly drive cognitive dysfunction and propose a hierarchically targeted nanotherapy for related comorbidities.
Alveolar bone defects, including dehiscence and fenestration, are commonly encountered in adult patients seeking orthodontic treatment. These anatomical deficiencies increase the risk of periodontal complications and may significantly compromise orthodontic tooth movement. Alveolar bone defects can also develop during orthodontic treatment, particularly in adult patients with narrow alveolar ridges requiring excessive tooth movement. Orthodontic-associated alveolar ridge augmentation (OARA) is an effective treatment approach that provides additional bone support and facilitates tooth movement, thereby reducing the incidence of periodontal complications and accelerating and broadening the scope of movement. At present, standardized diagnostic and treatment protocols for OARA in adult patients are lacking. This expert consensus aims to provide evidence-based recommendations for OARA in adult patients. A multidisciplinary panel of 27 experts conducted a Delphi-style process incorporating a targeted literature review and three voting rounds, achieving ≥70% agreement. Twenty-nine consensus statements across seven clinical domains, including pre-OARA examination, indications, bone graft material selection, timing, surgical protocols, standard operating procedures and considerations, were established with recommendations graded according to adapted GRADE criteria. This report presents a structured clinical framework for OARA and identifies future research priorities.
Adenoid hypertrophy is a common cause of pediatric obstructive sleep apnea (OSA), which can impair cognitive development and affect craniofacial development. Given that adenoids typically regress with age and may respond to oral appliance therapy, early identification, clear orthodontic indications, and timely referral are essential for effective management. A major challenge in this process is accurately assessing adenoid volume and quantifying nasopharyngeal obstruction in three dimensions. To address this, we developed a deep learning–based method using cone-beam computed tomography (CBCT) to accurately segment adenoid, and establish a novel quantitative index, the Three-Dimensional Adenoidal–Nasopharyngeal Ratio (3D-AN), for assessing nasopharyngeal airway obstruction. This retrospective study included three datasets. Dataset 1 comprised 126 CBCT scans (pre- and post-adenoidectomy) from 63 pediatric OSA patients. Dataset 2 included post-adenoidectomy CBCT scans of 26 pediatric OSA patients. Dataset 3 involved 161 pediatric patients with both polysomnography and CBCT data. A SegResNet-based model was trained on Datasets 1 and 2 (1326 training pairs) to predict postoperative airway morphology following adenoidectomy using preoperative scans. By inputting preoperative airway data, the model predicts postoperative morphology, and the volumetric difference represents the adenoid. 3D-AN ratio was then computed from adenoid-to-nasopharyngeal volume. Dataset 3 was used to investigate the relationship between the 3D-AN and pediatric OSA. The segmentation model achieved a Dice similarity coefficient of 0.88 and a relative volume error of 0.09. Preliminary analysis showed that a 3D-AN ratio below 0.18 was not significantly correlated with pediatric OSA, while values above 0.18 correlated significantly with OSA (r = 0.56, P < 0.01). This automated method enables accurate adenoid segmentation. The proposed 3D-AN, based on volumetric ratios, holds potential for early detection of adenoid-related airway obstruction and for supporting future research in adenoid assessment and clinical management.
Oral health management during orthodontic treatment is crucial for ensuring the effectiveness of the treatment. Proper oral health management can accelerate the orthodontic process, alleviate adverse reactions, and improve quality of life. Currently, there is a lack of systematic and comprehensive guidance on oral health management for patients undergoing orthodontic treatment both domestically and internationally. To further standardize oral health management during the orthodontic period, this paper summarized relevant literature from home and abroad through discussions among experts, established health management protocols for fixed, invisible, and functional orthodontics, aiming to provide references and guidance for orthodontists and patients.
INTRODUCTION:Hyperdivergent skeletal class II malocclusion in adolescents is characterised by mandibular retrognathia with excessive vertical growth and clockwise mandibular rotation, which can worsen facial profile and airway-related morphology. Although mandibular advancement approaches are commonly used, they may increase the vertical dimension and are suboptimal for patients with long-face patterns. This randomised controlled trial aims to evaluate a micro-implant-assisted protrusion correction technique designed to flatten the occlusal plane and promote counterclockwise mandibular rotation, thereby improving facial profile and pharyngeal space. METHODS AND ANALYSIS:This trial is registered at the Chinese Clinical Trial Registry (ChiCTR; ChiCTR2100054105). This is a two-arm, multicentre, randomised, parallel-controlled trial. Ninety adolescents will be recruited from Shanghai Stomatological Hospital, Zhongshan Hospital (Fudan University), and Xinhua Hospital (Shanghai Jiao Tong University School of Medicine), and will be randomly allocated (1:1) to the test or control group. The control group will receive conventional anterior teeth retraction, whereas the test group will receive a micro-implant-assisted vertical control protocol with occlusal plane flattening. The primary outcome is the change in the A point-nasion-B point angle. Secondary outcomes include changes in the occlusal plane, incisor and molar heights, and facial height. Measurements will be assessed at baseline, at the end of treatment and at 12 months after treatment completion. ETHICS AND DISSEMINATION:This study was approved by the Ethics Committee of the Shanghai Stomatological Hospital (approval no. (2022)006). The results of this study will be made available in peer-reviewed journals. TRIAL REGISTRATION NUMBER:ChiCTR2100054105.
Chronic intermittent hypoxia (CIH), the cardinal pathophysiological feature of obstructive sleep apnea, is increasingly recognized as an important modifier of metabolic dysfunction-associated steatotic liver disease (MASLD), but the underlying mechanisms remain incompletely understood. In this study, male C57BL/6 mice were fed a standard diet or a high-fat diet (HFD) and exposed to normoxia or CIH for 8 weeks. Histological, ultrastructural, biochemical, transcriptomic, proteomic, and metabolomic analyses were integrated to characterize hepatic alterations induced by CIH under metabolic stress. CIH markedly aggravated HFD-induced liver injury, as evidenced by increased body fat, hepatomegaly, serum transaminases, steatosis, mitochondrial ultrastructural alterations, and inflammatory infiltration. Mechanistically, CIH promoted hepatic lipid metabolic reprogramming by suppressing the PPARα/CPT1A fatty acid β-oxidation axis while enhancing the SREBP-1c/FASN/PLIN2 lipogenic pathway, impaired the Nrf2/HO-1/SLC7A11/GPX4 antioxidant defense system, increased lipid peroxidation and iron accumulation, and activated NF-κB/NLRP3 signaling. These findings support a multifactorial model in which CIH functions as an additional hypoxic stressor that exacerbates HFD-induced MASLD-like liver injury through coordinated metabolic, oxidative, and inflammatory dysregulation.
Periodontal tissue regeneration in chronic periodontitis associated with diabetes mellitus (CPDM) remains challenging. Oxidative stress and host immune dysregulation driven by hyperglycemia further exacerbate periodontal tissue destruction. Therefore, strategies that reduce oxidative stress and remodel the periodontal immune microenvironment are critical for promoting periodontal regeneration in CPDM. However, the application of supramolecular hydrogels in CPDM therapy remains largely unexplored. In this study, a novel proanthocyanidin B2-based adenosine supramolecular hydrogel-guanosine-adenosine-proanthocyanidin B2 (GAOPCB2)-was developed to enhance tissue regeneration in CPDM. Proanthocyanidin B2 exhibited potent reactive oxygen species (ROS)-scavenging and anti-inflammatory properties, promoting both HUVEC tube formation and stem cell osteogenic differentiation. The natural nucleoside adenosine further enhanced the osteogenic differentiation of stem cells. These findings indicate that the biomimetic GAOPCB2 supramolecular hydrogel possesses robust ROS-scavenging, anti-inflammatory, and osteogenic properties. Therefore, this multifunctional scaffold represents a promising platform for periodontal tissue regeneration in inflammatory environments. As demonstrated by both the in vitro and in vivo findings, the GAOPCB2 hydrogel is a promising therapeutic candidate for CPDM.
Periodontitis is a prevalent chronic inflammatory disease driven by oral microbiota dysbiosis, with profound oral and systemic impacts that impair healthy aging. Conventional periodontal assessment requires calibrated clinical examination, is time-consuming, and may cause discomfort or bleeding on probing, which limits its scalability for community-based screening. Microbiota-based strategies therefore show promise for accessible screening; however, the roles of oral niche heterogeneity and age-related microbial shifts remain unclear. A total of 120 participants were classified into low-risk/non-periodontal (NP, n = 67) and high-risk/periodontal (P, n = 53) groups according to a CPI-based index-tooth periodontal risk screening protocol combined with panoramic radiographic assessment. Easily accessible oral samples (saliva, supragingival dental plaque, and tongue coating) were collected for 16S rRNA gene sequencing. Bioinformatic analyses and machine-learning models were used to evaluate diagnostic efficacy, with age stratification (< 50 years vs. ≥ 50 years). Age differed significantly between the NP and P groups in the overall cohort (p = 0.004, t test). After age stratification, no significant within-stratum age differences were observed between the two periodontal groups (< 50 years: p = 0.122; ≥ 50 years: p = 0.948). Non-age-stratified exploratory models showed moderate but variable discriminatory performance, with LOOCV AUCs ranging from 0.616 to 0.740. After age stratification, the niche-specific models showed moderate and relatively consistent performance, with LOOCV AUCs ranging from 0.759 to 0.786 in the < 50-year stratum and from 0.749 to 0.760 in the ≥ 50-year stratum. Although several age-stratified models showed numerically higher AUCs than the corresponding non-age-stratified models, this apparent improvement should be interpreted cautiously because of the reduced subgroup sample sizes. Pairwise DeLong tests showed no statistically significant AUC differences among saliva, supragingival dental plaque, and tongue coating in either the non-age-stratified or age-stratified analyses. Accounting for age-related microbial variation may contribute to more consistent performance of microbiota-based periodontal screening models. However, the three accessible oral niches showed comparable moderate performance, and no single niche demonstrated statistically significant superiority. These findings are preliminary and require validation in larger, multicenter cohorts with independent external validation.
Rationale: Obstructive sleep apnea (OSA), characterized by chronic intermittent hypoxia (CIH), has emerged as a risk factor for Parkinson's Disease (PD). Yet, whether CIH increases PD susceptibility and the underlying mechanisms remain elusive. Methods: To investigate the impact of CIH on PD susceptibility, we established a series of subtoxic PD models subjected to CIH conditions. We analyzed lipid metabolism, with a particular focus on lipid droplets (LDs), in the pathogenesis of CIH-induced PD. Furthermore, we examined the significance of LD-mitochondrial interactions in mediating aberrant LD accumulation within dopaminergic (DA) neurons and identified the tethering proteins implicated in this process. Additionally, we utilized both systemic and region-specific modulation of the peroxisome proliferator-activated receptor α (PPARα) pathway to assess the neuroprotective potential of restoring LD-mitochondrial coupling in PD models. Results: We revealed that CIH significantly exacerbated nigrostriatal DA neurodegeneration and motor dysfunction in subtoxic PD models. Mechanistically, we identified a PPARα-dependent disruption of Mfn2-Plin5 tethering, which impaired LD-mitochondrial interactions, thereby compromising LD turnover and promoting pathological LD accumulation within DA neurons. Crucially, pharmacological interventions targeting the LD-mitochondrial axis, including strategies to enhance LD catabolism, inhibit mitochondrial fission, or restore LD-mitochondrial tethering, effectively mitigated nigrostriatal DA neurodegeneration in CIH-preconditioned subtoxic PD models. Conclusions: This study reveals a previously unrecognized LD-mitochondrial regulatory axis underlying CIH-associated PD pathology and highlights its potential as a therapeutic target against CIH-accelerated neurodegeneration.
The prevalence of sleep-disordered breathing (SDB) among urban children aged 3 to 11 years remains insufficiently characterized. In addition, population-based screening lacks well-defined risk profiles, particularly in East Asian populations. This study aimed to estimate the prevalence of questionnaire-defined risk of SDB across pediatric age groups and to identify associated craniofacial and occlusal phenotypic patterns. A cross-sectional study was conducted in Shanghai, China, using a randomized cluster sampling approach among children aged 3–11 years. Clinical examinations by dental professionals assessed craniofacial morphology, dental occlusion, and tonsillar size. Additional data were collected on sociodemographic characteristics, medical history, and parent-reported responses to the PSQ-22 and OSA-18 sleep questionnaires. A two-step cluster analysis was performed to automatically classify participants into subgroups based on shared clinical and demographic features. A total of 1,624 children from 31 schools were included in the analysis, with 14.78
Diverse immuno-inflammatory disorders are typically caused by dysregulated immunoactivation and the consequently chronic tissue inflammation. However, current therapeutics have exhibited mixed success due to either inherent inefficacy or limited localized tissue retention. Holistic approaches capable of integrating multipotent biotherapeutics with their optimized bioavailability in inflamed sites remain highly demanded for refractory inflammation management. Herein, dually matrix-binding platelet backpacking extracellular vesicles from myeloid-derived suppressor cells (A5/PLT-MDEV) is reported to mediate superior tissue residence of MDEVs to sustain localized immune reprogramming to durably alleviate inflammation. Scalability of the facile synthesis method, from using cell line-derived platelets to exploiting primary stem cell-derived platelets, has been demonstrated. Owing to integrin alpha 5 overexpression and inherent characteristic, MDEV-decorated engineered platelets concurrently bind fibronectin and collagen in inflamed tissues, shelter MDEVs from macrophage uptake, and serve as micro-depots to confer on-demand release, collectively assisting backpacked MDEVs to reside locally for at least 10 days in mouse periodontitis and arthritis lesions. Such extended localized bioavailability of A5/PLT-MDEV enables a single dosage to allow MDEVs to lastingly reshape immune micro-environment in mouse periodontitis and arthritis, including upregulating Treg cells and suppressing pro-inflammatory T cells. Hence, A5/PLT-MDEV exhibits potent capacity in mitigating systemic and local inflammation. Compromised tissue homeostasis is consequently restored to rescue aggravation of these diseases. Dually tissue-anchoring platelet proposes a universal platform to develop spatiotemporally retaining therapeutics for safe and efficacious management of inflammation-accompanied conditions.
Sleep disorders (SDs), a public health concern, can lead to critical physiological conditions, and are associated with mental and behavior problems such as psychosocial stress, smoking, alcohol consumption, etc. This study aimed to investigate the cross-sectional associations between dentofacial deformities and sleep quality in young adults in China. Data were collected from 2,479 young adults (aged 17–25 years) enrolled at Fudan University across various regions of China. Participants completed a self-reported questionnaire that included general information and the Pittsburgh Sleep Quality Index (PSQI) under standardized guidance. Dentofacial characteristics were examined by experienced orthodontists. Data analysis employed one-way ANOVA, student’s t-test, chi-square tests, and multivariable logistic regression models. The study revealed a median PSQI score of 5.92 ± 1.66, with 16.3
This study aims to evaluate the effects of dentofacial orthopedic treatment (DOT) and adenotonsillectomy (AT) in Obstructive Sleep Apnea (OSA) children with skeletal Class II malocclusion and adenotonsillar hypertrophy (ATH), focusing on changes in sleep respiratory function, anatomic and aerodynamic characteristics of upper airway (UA). In this retrospective study, 38 OSA children (mean age: 8.42 years, 15 females and 23 males) were included consecutively. Patients were categorized into two groups: DOT group (n = 20) and AT group (n = 18). Baseline (T0) and follow-up (T1) assessments involved polysomnography and radiological examinations to evaluate improvements in sleep quality as well as changes in craniofacial morphology and UA variables. Aerodynamic parameters such as airflow velocity, airway resistance, and wall shear stress were quantified using computational fluid dynamics. In the comparative analysis of sleep respiratory functions, there were no significant differences in apnea-hypopnea index changes between the treatment groups (DOT group: -3.72/h, AT group: -3.32/h, P = 0.600). In the DOT group, UA’s volume average enlargements were observed in the nasopharynx, palatopharynx, glossopharynx, and hypopharynx by 54.5
The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Clear aligner treatment is a novel technique in current orthodontic practice. Distinct from traditional fixed orthodontic appliances, clear aligners have different material features and biomechanical characteristics and treatment efficiencies, presenting new clinical challenges. Therefore, a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique. This expert consensus discusses case selection and grading of treatment difficulty, principle of clear aligner therapy, clinical procedures and potential complications, which are crucial to the clinical success of clear aligner treatment.
Background/Objectives: Current approaches to monitoring obstructive sleep apnea (OSA) risk primarily focus on structural or functional abnormalities, often neglecting systemic metabolic and physiological factors. Resource-intensive methods, such as polysomnography (PSG), limit their routine applicability. This study aimed to evaluate composite nutritional-inflammatory indices derived from routine blood markers to identify feasible indices for OSA management and explore their association with OSA risk. Methods: Data from 9622 adults in the NHANES (2015-2020) and GWAS datasets were analyzed using logistic regression, restricted cubic splines, machine learning, and Mendelian randomization (MR). These techniques were employed to identify nutritional-inflammatory indices associated with OSA risk. Random forest modeling identified body mass index (BMI) and albumin (ALB) as key components of the advanced lung cancer inflammation index (ALI). Causal relationships between ALI components and OSA were validated using MR. Results: ALI was significantly associated with OSA, with individuals in the highest ALI tertile exhibiting a 59% higher likelihood of OSA (OR = 1.59, 95% CI: 1.38-1.84; p < 0.001). BMI and ALB were identified as key contributors to ALI and confirmed as causal risk factors for OSA (BMI: OR = 1.91, 95% CI: 1.80-2.02; ALB: OR = 1.11, 95% CI: 1.04-1.19). Age, gender, and the neutrophil-to-lymphocyte ratio (NLR) were also significant predictors. Conclusions: This study identifies ALI as a potential composite index for assessing OSA risk. Integrating statistical modeling, machine learning, and causal inference techniques highlights the utility of nutritional-inflammatory indices in improving OSA monitoring and management in clinical practice.