Multifunctional Metal-Phenolic Composites Promote Efficient Periodontitis Treatment via Antibacterial and Osteogenic Properties.

Periodontitis, a complex inflammatory disease initiated by bacterial infections, presents a significant challenge in public health. The increased levels of reactive oxygen species and the subsequent exaggerated immune response associated with periodontitis often lead to alveolar bone resorption and tooth loss. Herein, we develop multifunctional metal-phenolic composites (i.e., Au@MPN-BMP2) to address the complex nature of periodontitis, where gold nanoparticles (AuNPs) are coated by metal-phenolic networks (MPNs) and bone morphogenetic protein 2 (BMP2). In this design, MPNs exhibit remarkable antibacterial and antioxidant properties, and AuNPs and BMP2 promote osteogenic differentiation of bone marrow mesenchymal stem cells under inflammatory conditions. In a rat model of periodontitis, treatment with Au@MPN-BMP2 leads to notable therapeutic outcomes, including mitigated oxidative stress, reduced progression of inflammation, and the significant prevention of inflammatory bone loss. These results highlight the multifunctionality of Au@MPN-BMP2 nanoparticles as a promising therapeutic approach for periodontitis, addressing both microbial causative factors and an overactivated immune response. We envision that the rational design of metal-phenolic composites will provide versatile nanoplatforms for tissue regeneration and potential clinical applications.

A whole-course-repair system based on ROS/glucose stimuli-responsive EGCG release and tunable mechanical property for efficient treatment of chronic periodontitis in diabetic rats.

Elevated glucose levels, multiple pro-inflammatory cytokines and the generation of excessive reactive oxygen species (ROS) are pivotal characteristics within the microenvironments of chronic periodontitis with diabetes mellitus (CPDM). Control of inflammation and modulation of immune system are required in the initial phase of CPDM treatment, while late severe periodontitis requires a suitable scaffold to promote osteogenesis, rebuild periodontal tissue and reduce alveolar bone resorption. Herein, a whole-course-repair system is introduced by an injectable hydrogel using phenylboronic acid functionalized oxidized sodium alginate (OSA-PBA) and carboxymethyl chitosan (CMC). Epigallocatechin-3-gallate (EGCG) was loaded to simultaneously adjust the mechanical property of the OSA-PBA/CMC + EGCG hydrogel (OPCE). This hydrogel has distinctive adaptability, injectability, and ROS/glucose-triggered release of EGCG, making it an ideal drug delivery carrier. As expected, OPCE hydrogel shows favourable antioxidant and anti-inflammatory properties, along with a regulatory influence on the phenotypic transition of macrophages, providing a favourable immune microenvironment. Apart from that, it provides a favourable mechanical support for osteoblast/osteoclast differentiation regulation at the late proliferation stage of periodontal regeneration. The practical therapeutic effects of OPCE hydrogels were also confirmed when applied for treating periodontitis in diabetic rats. In summary, OPCE hydrogel may be a promising whole-course-repair system for the treatment of CPDM.

Sema3A secreted by sensory nerve induces bone formation under mechanical loads.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A (Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement (OTM) model. Firstly, bone formation was activated after the 3rd day of OTM, coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor (NGF), highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells (hPDLCs) within 24 hours. Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.

Evaluation of optimal anterior-posterior position of upper incisors through ANS point: a retrospective study on a Chinese sample.

OBJECTIVES: This study was designed to determine the optimal anterior-posterior (AP) position of upper incisors through Anterior Nasal Spine (ANS) point. MATERIALS AND METHODS: Lateral cephalometric radiographic images of 690 patients were collected and divided into a derivation group and a validation group, and the former were subdivided into a proper AP position (PAP) group and an improper AP position (iPAP) group. The distance from facia-axis (FA) point of upper incisors to the line perpendicular to Frankfort horizontal (FH) plane through ANS (FA-ANS) was measured, and the relationship between FA-ANS and several cephalometric indices were studied through Pearson correlation analysis. Receiver operating characteristic (ROC) curves for different clinical indices were analyzed to evaluate the diagnostic efficiency of optimal AP position of upper incisors. RESULTS: The average value of FA-ANS in PAP group was 0.57±1.99, which was significantly different from FA-ANS in iPAP group. Cephalometric indices such as U1-NA, U1-SN, AB-NPo, UL-TVL, Wits, and ANB were found to be correlated with FA-ANS. The receiver operating characteristic (ROC) curves represented a greater diagnostic efficiency of FA-ANS compared with other clinical indices. CONCLUSIONS: ANS point, as a stable skeletal landmark, could be used to access an optimal AP position of upper incisors, providing aids to clinical diagnosis and treatment goal determination for clinical practice. CLINICAL RELEVANCE: A new index FA-ANS, together with other traditional indices, could help determine the optimal position of upper incisors and provide a personalized therapeutic plan.

Accuracy in predicting soft tissue changes of orthodontic class III cases using Dolphin® software.

OBJECTIVES: The prediction of posttreatment outcomes is conducive to the final determination of ideal therapeutic options. However, the prediction accuracy in orthodontic class III cases is unclear. Therefore, this study conducted exploration on prediction accuracy in orthodontic class III patients using the Dolphin® software. MATERIALS AND METHODS: In this retrospective study, lateral cephalometric radiographs of pre- and posttreatment were collected from 28 angle class III adults who received completed non-orthognathic orthodontic therapy (8 males, 20 females; mean age = 20.89 ± 4.26 years). The values of 7 posttreatment parameters were recorded and inserted into the Dolphin® Imaging software to generate a predicted outcome, and then the prediction radiograph and actual posttreatment radiograph were superimposed and compared in terms of soft tissue parameters and landmarks. RESULTS: The prediction showed significant differences with the actual outcomes in nasal prominence (the difference between the prediction and the actual value was - 0.78 ± 1.82 mm), the distance from the lower lip to the H line (0.55 ± 1.11 mm), and the distance from the lower lip to the E line (0.77 ± 1.62 mm) (p < 0.05). Point subnasale (Sn) (an accuracy of 92.86% in the horizontal direction and 100% in the vertical direction in 2 mm) and point soft tissue A (ST A) (an accuracy of 92.86% in the horizontal direction and 85.71% in the vertical direction in 2 mm) were proven to be the most accurate landmarks, while the predictions in the chin region were relatively inaccurate. Furthermore, the predictions in the vertical direction were of higher accuracy compared to the horizontal direction except for the points around the chin. CONCLUSIONS: The Dolphin® software demonstrated acceptable prediction accuracy in midfacial changes in class III patients. However, there were still limitations for changes in the chin and lower lip prominence. CLINICAL RELEVANCE: Clarifying the accuracy of Dolphin® software in predicting soft tissue changes of orthodontic class III cases will facilitate physician-patient communication and clinical treatment.

Evaluation of automated detection of head position on lateral cephalometric radiographs based on deep learning techniques.

BACKGROUND: Lateral cephalometric radiograph (LCR) is crucial to diagnosis and treatment planning of maxillofacial diseases, but inappropriate head position, which reduces the accuracy of cephalometric measurements, can be challenging to detect for clinicians. This non-interventional retrospective study aims to develop two deep learning (DL) systems to efficiently, accurately, and instantly detect the head position on LCRs. METHODS: LCRs from 13 centers were reviewed and a total of 3000 radiographs were collected and divided into 2400 cases (80.0 %) in the training set and 600 cases (20.0 %) in the validation set. Another 300 cases were selected independently as the test set. All the images were evaluated and landmarked by two board-certified orthodontists as references. The head position of the LCR was classified by the angle between the Frankfort Horizontal (FH) plane and the true horizontal (HOR) plane, and a value within - 3°- 3° was considered normal. The YOLOv3 model based on the traditional fixed-point method and the modified ResNet50 model featuring a non-linear mapping residual network were constructed and evaluated. Heatmap was generated to visualize the performances. RESULTS: The modified ResNet50 model showed a superior classification accuracy of 96.0 %, higher than 93.5 % of the YOLOv3 model. The sensitivity&recall and specificity of the modified ResNet50 model were 0.959, 0.969, and those of the YOLOv3 model were 0.846, 0.916. The area under the curve (AUC) values of the modified ResNet50 and the YOLOv3 model were 0.985 ± 0.04 and 0.942 ± 0.042, respectively. Saliency maps demonstrated that the modified ResNet50 model considered the alignment of cervical vertebras, not just the periorbital and perinasal areas, as the YOLOv3 model did. CONCLUSIONS: The modified ResNet50 model outperformed the YOLOv3 model in classifying head position on LCRs and showed promising potential in facilitating making accurate diagnoses and optimal treatment plans.

The interplay between the nerves and skeleton: a 30-year bibliometric analysis.

Background: The mechanisms and effects of the interplay between the nerves and skeleton remain a popular research topic. This study aimed to analyze and evaluate publications on nerve-bone interactions using bibliometrics and to identify the state of the art of current research, hotspots, and future directions. Methods: This study included 1989 articles and reviews from the Web of Science Core Collection (WoSCC) published from January 1, 1991, to June 22, 2022. The Bibliometrix package of R 4.2.0 (The R Foundation for Statistical Computing, Vienna, Austria) was used to analyze basic information about the publications, including the annual number of publications, institution analysis, author influence analysis, journal analysis, and the national cooperation network. We also used CiteSpace 5.8.R3 for bibliometric analysis, including co-occurrence, co-citation, and cluster analysis. Results: We discovered a significant increase in the number of articles on nerve-bone interactions published over the last 10 years. The most active country and institution were the United States and the University of Minnesota, respectively. In terms of journals and cocited journals, Bone was ranked highest with respect to the number of publications, while Journal of Bone and Mineral Research was ranked highest among cited journals. Wang Lei was the author with the most publications, and Bjurholm A was the most cited author. The analysis of references and keywords revealed that the impact of nerve- and neuromodulation-related factors on stem cell differentiation was a persistently hot topic. Osteoarthritis, neuropeptide Y, and osteoclastogenic process are likely to be the next era of research hotspots. The neurovascular crosstalk within bone has received great attention, especially in skeletal diseases, which may provide potential targets for future treatments. Conclusions: We used a bibliometric method to provide an efficient, objective, and comprehensive assessment of existing research about the interplay between the skeletal and nervous systems and to accurately identify hotspots and research frontiers, providing valuable information for future research.

A simple method for quick evaluation of the anterior tooth ratio: an observational study.

BACKGROUND: An ideal relationship of anterior teeth is closely related to postoperative function, stability, and aesthetics. Therefore, it is necessary to estimate the proportion of anterior teeth when communicating with patients about possible treatment plans and outcomes. This study aimed to establish a simple method for assessing the proportion of anterior teeth and to identify the standard ratio value to provide references for clinical work. METHODS: Five hundred fourteen patients were divided into derivation, standard, and validation datasets. We first deduced our novel simplified anterior tooth ratio (SATR) by finding the key teeth with the derivation datasets, then established standard values by measuring the standard models, and finally validated the diagnostic performance of SATR. Independent sample t-test was used to select key teeth. Pearson's correlation analysis and linear regression analysis was used to test and verify the correlation between SATR and the anterior Bolton ratio. Chi-square test and diagnostic test were used to verify the diagnostic results using SATR. P values of < 0.05 were considered statistically significant. RESULTS: Patients with an abnormal anterior Bolton ratio were more likely to have variations in the maxillary and mandibular lateral incisors. Therefore, the ratio of maxillary and mandibular lateral incisors was chosen as a simple way to assess the anterior tooth ratio and was defined as SATR (simplified anterior tooth ratio). A positive correlation was observed between SATR and anterior Bolton ratio (r = 0.702, p < 0.001), with the linear regression equation as follows: y = 0.503 + 0.328x, x = SATR, y = anterior Bolton ratio. The standard value of SATR was established (85.69% ± 3.57%) and proven reliable in clinical practice. CONCLUSIONS: The ratio of maxillary and mandibular lateral incisors can be used to estimate the anterior tooth ratio, which showed high reliability and efficiency.

Enhanced PDGFR/Wnt/ß-catenin activity of mesenchymal stem cells with high migration ability rescue bone loss of osteoporosis.

Osteoporosis is a widespread disease characterized by bone mass loss and microarchitectural deterioration. The side effects of clinical drugs make mesenchymal stem cells (MSCs)-based therapy gain increasing focus in the treatment of osteoporosis. MSCs need to migrate to the site of damage and undergo differentiation in order to participate in the subsequent bone repair process. Therefore, the homing ability of MSCs may be related to the repair ability. Here, we proposed a novel method to screen MSCs with high migration capacity and confirmed that these MSCs exhibited higher osteogenic differentiation ability both in vivo and in vitro. Further results indicated that MSCs with high migration ability could partly rescue the bone loss of ovarectomized (OVX) rats. Higher expression of Platelet-derived growth factors receptor ß- (PDGFRß) and more nuclear transduction of ß-catenin in MSCs with high migration ability may be responsible for biological functions. This article may provide a method to improve the efficacy of MSCs-based therapy in the clinic.

Diagnostic validity of different gonial angle segmentation for the assessment of mandibular growth direction: A retrospective study.

BACKGROUND: The development of the mandible largely determines the sagittal and vertical lateral appearance. The gonial angle (Articulare-Gonion-Menton, Ar-Go'-Me), as a composite indicator, represents the growth direction of the mandible. We proposed a method based on the Frankfort horizontal (FH) plane and its vertical plane (VFH) to divide the gonial angle into sagittal and vertical components (Articulare-Gonion-VFH / Menton-Gonion-FH, Ar-Go'-VFH / Me-Go'-FH) and to compare the accuracy of diagnosing the development of the mandible and maxillofacial structures with other methods. METHODS: Lateral cephalometric films from 736 volunteers aged 6-30 years were collected and analyzed for cephalometric measurements. Four groups of segmentation-based angle, including the FH-based segmentation (Ar-Go'-VFH / Me-Go'-FH), the SN-based segmentation (Articulare-Gonion- Sellion-Nasion plane' vertical plane/ Menton-Gonion- Sellion-Nasion plane, Ar-Go'-VSN / Me-Go'-SN), the Go'-S based segmentation(Articulare-Gonion-Sellion / Menton-Gonion-Sellion, Ar-Go'-S / Me-Go'-S), and the Go'-N based segmentation (Articulare-Gonion-Nasion / Menton-Gonion-Nasion, Ar-Go'-N / Me-Go'-N), as well as commonly used sagittal and vertical indices were measured. Pearson correlation analysis was used to show the representativeness of different segmentation methods on the mandibular growth direction. RESULTS: As the gonial angle decreased with age, all the segmentation-based metrics decreased. The plane-based segmentation metrics, including Ar-Go'-VFH / Me-Go'-FH, Ar-Go'-VSN / Me-Go'-SN, were superior to the point-based segmentation metrics (Ar-Go'-S / Me-Go'-S, and Ar-Go'-N / Me-Go '-N) in evaluating vertical and sagittal development of the mandible. The sagittal indicators displayed alteration of ramus and condyle, while these vertical indicators responded to the alteration of the mandibular corpus and gonial angle. CONCLUSIONS: The gonial angle should be clinically segmented with planes (including SN plane and FH plane) rather than points (including Go'-S and Go'-N) to assess mandibular development. The FH plane-based segmentation method facilitated chair-side diagnosis of the mandibular growth direction.

Orthodontic emergencies and mental state of Chinese orthodontic patients during the COVID-19 pandemic.

BACKGROUND: The ongoing COVID-19 pandemic postponed routine follow-up visits of many orthodontic patients, which compromised their treatment process and mental states. This study was aimed to assess orthodontic emergency occurrence and psychological states of Chinese orthodontic patients during this pandemic. METHODS: Orthodontic patients in China were invited to answer an anonymous online questionnaire from February 20, 2020 to March 5, 2020, when routine dental care was suspended in China. The questionnaire included self-assessment of oral hygiene and compliance, orthodontic emergencies, perceptions and feelings about COVID-19 and anxiety self-rating scale, etc. Collected data was statistically analyzed with Chi-square, independent t test and univariable generalized estimating equations regression analysis. RESULTS: A total of 1078 respondents (292 male; 786 female) from 30 provinces of China were included in this study. About one-third (33.67%) of patients reported that they encountered orthodontic problems during the pandemic. Patients with clear aligners reported fewer orthodontic problems than those with fixed appliances or removable appliances. Female patients, elder patients and patients who encountered orthodontic emergencies were more anxious than other patients. CONCLUSIONS: The compliance and occurrence of orthodontic emergencies differed in patients with different orthodontic appliances. Patients with orthodontic emergencies exhibited higher anxiety states.

[Advances in the application of machine learning in maxillofacial cysts and tumors].

The application of artificial intelligence in medicine has gradually received attention along with its development. Many studies have shown that machine learning has a wide range of applications in stomatology, especially in the clinical diagnosis and treatment of maxillofacial cysts and tumors. This article reviews the application of machine learning in maxillofacial cyst and tumor to provide a new method for the diagnosis of oral and maxillofacial diseases.

[Advances in oral bacteria influencing host epigenetic regulation].

Epigenetics refers to a steady change in the level of gene expression caused by non-DNA sequence changes. Microbes can modulate host inflammation through epigenetic pathways to evade or expend immune responses. As an important part of human microbes, oral bacteria also have various epigenetic regulation mechanisms to affect host inflammatory responses. This article reviews the common pathways of epigenetic regulation in microbe infection and the regulation of host epigenetics by using oral microbes to provide a reference for the study of epigenetic-related mechanisms in oral diseases.

Prognostic Correlation of an Autophagy-Related Gene Signature in Patients with Head and Neck Squamous Cell Carcinoma.

Considerable evidence indicates that autophagy plays a vital role in the biological processes of various cancers. The aim of this study is to evaluate the prognostic value of autophagy-related genes in patients with head and neck squamous cell carcinoma (HNSCC). Transcriptome expression profiles and clinical data acquired from The Cancer Genome Atlas (TCGA) database were analyzed by Cox proportional hazards model and Kaplan-Meier survival analysis to screen autophagy-related prognostic genes that were significantly correlated with HNSCC patients' overall survival. Functional enrichment analyses were performed to explore biological functions of differentially expressed autophagy-related genes (ARGs) identified in HNSCC patients. Six ARGs (EGFR, HSPB8, PRKN, CDKN2A, FADD, and ITGA3) identified with significantly prognostic values for HNSCC were used to construct a risk signature that could stratify patients into the high-risk and low-risk groups. This signature demonstrated great value in predicting prognosis for HNSCC patients and was indicated as an independent prognostic factor in terms of clinicopathological characteristics (sex, age, clinical stage, histological grade, anatomic subdivision, alcohol history, smoking status, HPV status, and mutational status of the samples). The prognostic signature was also validated by data from the Gene Expression Omnibus (GEO) database and International Cancer Genome Consortium (ICGC). In conclusion, this study provides a novel autophagy-related gene signature for predicting prognosis of HNSCC patients and gives molecular insights of autophagy in HNSCC.

CLPNet: Cleft Lip and Palate Surgery Support With Deep Learning.

Cleft lip and palate is the most common congenital malformation in oral and maxillofacial region. As a kind of facial plastic surgery, the most important factor for the success of cleft lip and palate repair surgery is the design of surgical markers and incisions. However, general hospitals especially in rural areas lack dependable medical resources, which makes the effect of the surgery hard to guarantee. To solve this problem, we propose a novel robotic surgery assistant technology based on deep learning to help reduce the technical threshold and improve the overall effect of cleft lip and palate repair surgery. For the first time, a robust dataset of cleft lip and palate cases is established, which can be used to train the model to locate surgical markers and incisions. Secondly, we build a strong baseline on this dataset by using state-of-the-art Hourglass architecture and residual learning, with two neoteric block designs, one of which enables stronger capability of generalization, while the other greatly reduces the complexity of the model, thus making efficient application possible. Finally, by comparing with other facial feature extraction methods, our models achieve the best results on multiple metrics, showing their strong superiority and adaptability on this task.