The performance of artificial intelligence models in generating responses to general orthodontic questions: ChatGPT vs Google Bard.

INTRODUCTION: This study aimed to evaluate and compare the performance of 2 artificial intelligence (AI) models, Chat Generative Pretrained Transformer-3.5 (ChatGPT-3.5; OpenAI, San Francisco, Calif) and Google Bidirectional Encoder Representations from Transformers (Google Bard; Bard Experiment, Google, Mountain View, Calif), in terms of response accuracy, completeness, generation time, and response length when answering general orthodontic questions. METHODS: A team of orthodontic specialists developed a set of 100 questions in 10 orthodontic domains. One author submitted the questions to both ChatGPT and Google Bard. The AI-generated responses from both models were randomly assigned into 2 forms and sent to 5 blinded and independent assessors. The quality of AI-generated responses was evaluated using a newly developed tool for accuracy of information and completeness. In addition, response generation time and length were recorded. RESULTS: The accuracy and completeness of responses were high in both AI models. The median accuracy score was 9 (interquartile range [IQR]: 8-9) for ChatGPT and 8 (IQR: 8-9) for Google Bard (Median difference: 1; P <0.001). The median completeness score was similar in both models, with 8 (IQR: 8-9) for ChatGPT and 8 (IQR: 7-9) for Google Bard. The odds of accuracy and completeness were higher by 31% and 23% in ChatGPT than in Google Bard. Google Bard's response generation time was significantly shorter than that of ChatGPT by 10.4 second/question. However, both models were similar in terms of response length generation. CONCLUSIONS: Both ChatGPT and Google Bard generated responses were rated with a high level of accuracy and completeness to the posed general orthodontic questions. However, acquiring answers was generally faster using the Google Bard model.

Advanced glycation end products impair bone marrow mesenchymal stem cells osteogenesis in periodontitis with diabetes via FTO-mediated N6-methyladenosine modification of sclerostin.

BACKGROUND: Diabetes mellitus (DM) and periodontitis are two prevalent diseases with mutual influence. Accumulation of advanced glycation end products (AGEs) in hyperglycemia may impair cell function and worsen periodontal conditions. N6-methyladenosine (m6A) is an important post-transcriptional modification in RNAs that regulates cell fate determinant and progression of diseases. However, whether m6A methylation participates in the process of periodontitis with diabetes is unclear. Thus, we aimed to investigate the effects of AGEs on bone marrow mesenchymal stem cells (BMSCs), elucidate the m6A modification mechanism in diabetes-associated periodontitis. METHODS: Periodontitis with diabetes were established by high-fat diet/streptozotocin injection and silk ligation. M6A modifications in alveolar bone were demonstrated by RNA immunoprecipitation sequence. BMSCs treated with AGEs, fat mass and obesity associated (FTO) protein knockdown and sclerostin (SOST) interference were evaluated by quantitative polymerase chain reaction, western blot, immunofluorescence, alkaline phosphatase and Alizarin red S staining. RESULTS: Diabetes damaged alveolar bone regeneration was validated in vivo. In vitro experiments showed AGEs inhibited BMSCs osteogenesis and influenced the FTO expression and m6A level in total RNA. FTO knockdown increased the m6A levels and reversed the AGE-induced inhibition of BMSCs differentiation. Mechanically, FTO regulated m6A modification on SOST transcripts, and AGEs affected the binding of FTO to SOST transcripts. FTO knockdown accelerated the degradation of SOST mRNA in presence of AGEs. Interference with SOST expression in AGE-treated BMSCs partially rescued the osteogenesis by activating Wnt Signaling. CONCLUSIONS: AGEs impaired BMSCs osteogenesis by regulating SOST in an m6A-dependent manner, presenting a promising method for bone regeneration treatment of periodontitis with diabetes.

Flash-free and conventional adhesive ceramic brackets in patients undergoing orthodontic treatment: A systematic review and meta-analysis.

To investigate whether flash-free adhesive ceramic brackets (FFA) have a better clinical performance than conventional adhesive ceramic brackets (CVA) in patients undergoing multi-bracket orthodontic treatment. PubMed, CENTRAL, Web of Science, Scopus, Embase, CNKI and Grey-literature were searched without restrictions up to January 2022. Both randomized controlled trials (RCTs) and controlled clinical trials (CCTs) were included. Risk of bias assessment was performed using the RoB 2.0 and ROBINS-I cochrane risk of bias tools. Eight articles, for seven studies, were included in this systematic review, and four split-mouth trials (SMT) were included in the meta-analysis. A random-effects meta-analysis found a statistically significant faster bonding time with FFA (mean difference [MD] = -93.85 seconds/quadrant, P = .002, 2 SMT), and no statistically significant difference regarding bracket failure rate at 6 months (risk ratio [RR] = 1.05; P = .93, 3 SMT), adhesive removal time (MD = -18.26 seconds/quadrant, P = .50, 2 SMT), and amount of remnant adhesive (MD = -0.13/bracket, P = .72, 2 SMT) between FFA and CVA. No difference (P > .05, 3 SMT) was found in enamel demineralization and periodontal measurements. CVA showed a statistically significant higher debonding pain score (P = .004, 1 SMT). Both flash-free and conventional adhesive ceramic brackets had a similar clinical performance, except for the faster bonding with FFA. Further, well-designed clinical trials are still required.

Sex difference in incidence of major depressive disorder: an analysis from the Global Burden of Disease Study 2019.

BACKGROUND: Major depressive disorder (MDD) is a leading mental disorder causing severe impairment. This study was aimed to evaluate sex difference in global MDD incidence by year, age, and socioeconomic status, according to the Global Burden of Disease Study 2019 (GBD 2019). METHODS: Global and national sex-specific incidence estimates of MDD, from 1990 to 2019, in different age groups, were extracted from the GBD 2019. Socioeconomic development index (SDI) as an indicator of national socioeconomic development was used. Absolute (female minus male) and relative (female to male ratio) sex difference in age-standardized incidence rates (ASRs), as well as risk ratios (RR and 95% confidence interval), were computed by year and age. Linear regression analyses were conducted to investigate socioeconomic-associated sex difference in incidence. RESULTS: Absolute and relative sex difference in ASRs showed a slight declining trend during 1990 and 2019, with absolute difference decreasing from 1818.23 to 1602.58, and relative difference decreasing from 1.71 to 1.61. Worldwide, females had a higher risk of MDD than males in 1990 (RR: 1.706 (1.705-1.706)) and 2019 (RR: 1.602 (1.619-1.620)). The highest RRs were observed in the Region of the Americas. Sex difference in incidence rates increased rapidly with age for those under 20 years old. The highest RR (1.913 (1.910-1.915)) was observed in the age group of 10-14. Relative sex difference had a significant positive relationship with SDI (standardized ß = 0.267, P < 0.001). CONCLUSIONS: Despite that slight improvement in sex difference in global MDD incidence has been achieved, sex difference still persists in the past decades, with females always having a higher incidence than males. Greater sex difference was found at younger ages and in more developed countries. The findings highlight the importance of making sex-specific health policy to reduce sex difference in MDD incidence.

Hyperglycemia Aggravates Periodontitis via Autophagy Impairment and ROS-Inflammasome-Mediated Macrophage Pyroptosis.

Macrophage pyroptosis drives the secretion of IL-1ß, which has been recently reported to be a featured salivary biomarker for discriminating periodontitis in the presence of diabetes. This study aimed to explore whether macrophage pyroptosis plays a role in the development of diabetes mellitus-periodontitis, as well as potential therapeutic strategies. By establishing a model of experimental diabetes mellitus-periodontitis in rats, we found that IL-1ß and gasdermin D were highly expressed, leading to aggravated destruction of periodontal tissue. MCC950, a potent and selective molecule inhibitor of the NLRP3 inflammasome, effectively inhibited macrophage pyroptosis and attenuated alveolar bone losses in diabetes mellitus-periodontitis. Consistently, in vitro, high glucose could induce macrophage pyroptosis and thus promoted IL-1ß production in macrophages stimulated by lipopolysaccharide. In addition, autophagy blockade by high glucose via the mTOR-ULK1 pathway led to severe oxidative stress response in macrophages stimulated by lipopolysaccharide. Activation of autophagy by rapamycin, clearance of mitochondrial ROS by mitoTEMPO, and inhibition of inflammasome by MCC950 could significantly reduce macrophage pyroptosis and IL-1ß secretion. Our study demonstrates that hyperglycemia promotes IL-1ß production and pyroptosis in macrophages suffered by periodontal microbial stimuli. Modulation of autophagy activity and specific targeting of the ROS-inflammasome pathway may offer promising therapeutic strategies to alleviate diabetes mellitus-periodontitis.

The effect of early versus delayed space closure on the rate of orthodontic tooth movement: a systematic review and meta-analysis.

BACKGROUND: Orthodontic space closure of extraction sites can be initiated early, within 1-week post-extraction, or it can be delayed for a month or more. OBJECTIVE: This systematic review aimed to evaluate the effect of early versus delayed initiation of space closure after tooth extraction on the rate of orthodontic tooth movement. SEARCH METHODS: Unrestricted search of 10 electronic databases was conducted until September 2022. SELECTION CRITERIA: Randomized controlled trials (RCTs) investigating the initiation time of space closure of extraction sites in patients undergoing orthodontic treatment were included. DATA COLLECTION AND ANALYSIS: Data items were extracted using a pre-piloted extraction form. The Cochrane's risk of bias tool (ROB 2.0) and the Grading of Recommendations, Assessment, Development, and Evaluation approach were used for quality assessment. Meta-analysis was undertaken if there are at least two trials reporting the same outcome. RESULTS: Eleven RCTs met the inclusion criteria. Meta-analysis revealed that early canine retraction resulted in a statistically significant higher rate of maxillary canine retraction when compared to delayed canine retraction [mean difference (MD); 0.17 mm/month, 95% CI: 0.06 to 0.28, P = 0.003, 4 RCTs, moderate quality]. Duration of space closure was shorter in the early space closure group, but not statistically significant (MD; 1.11 months, 95% CI: -0.27 to 2.49, P = 0.11, 2 RCTs, low quality). The incidence of gingival invaginations was not statistically different between early and delayed space closure groups (Odds ratio; 0.79, 95% CI: 0.27 to 2.29, 2 RCTs, P = 0.66, very low quality). Qualitative synthesis found no statistically significant differences between the two groups regarding anchorage loss, root resorption, tooth tipping, and alveolar bone height. CONCLUSIONS: Based on the available evidence, early traction within the first week after tooth extraction has a minimal clinically significant effect on the rate of tooth movement compared to delayed traction. Further high-quality RCTs with standardized time points and measurement methods are still needed. REGISTRATION: PROSPERO (CRD42022346026).

The efficacy of concentrated growth factor and platelet-rich fibrin as scaffolds in regenerative endodontic treatment applied to immature permanent teeth: a retrospective study.

BACKGROUND: The aim of this retrospective study was to compare the efficacy of concentrated growth factor (CGF) and platelet-rich fibrin (PRF) as scaffolds in regenerative endodontic therapy (RET). METHODS: Necrotic immature permanent teeth treated with regenerative endodontic therapy during January 2018 to August 2022 were divided into the CGF and PRF groups according to the scaffold. The CGF and PRF groups included 7 and 6 teeth, respectively. The efficacy of regenerative endodontic therapy was analyzed based on the clinical and radiological outcomes at three different follow up periods: T1 (3-6 months), T2 (6-12 months) and T3 (12-24 months). Statistical analysis was performed using the independent T test, Mann-Whitney test and Fisher's exact test at a significance level of 0.05. RESULTS: The success rate of each stage in both groups was 100%. Through quantitative comparison of radiographic outcomes, there was no statistically significant difference between the two groups in terms of root development and periapical lesion healing at each stage, except that the increase rate of radiographic root area in PRF group in the T3 stage was above one in CGF group with statistically significance. CONCLUSIONS: Both CGF and PRF had a similar clinical performance regarding resolution of clinical signs and symptoms, periapical lesion healing, and continued root development as scaffolds in RET. Further prospective studies with large samples for longer follow-up periods are needed.

Three-dimensional analysis of the relationship between mandibular retromolar space and positional traits of third molars in non-hyperdivergent adults.

BACKGROUND: The anatomical position of the mandibular third molars (M3s) is located in the distal-most portions of the molar area. In some previous literature, researchers evaluated the relationship between retromolar space (RS) and different classifications of M3 in three­dimensional (3D) cone-beam computed tomography (CBCT). METHODS: Two hundred six M3s from 103 patients were included. M3s were grouped according to four classification criteria: PG-A/B/C, PG-I/II/III, mesiodistal angle and buccolingual angle. 3D hard tissue models were reconstructed by CBCT digital imaging. RS was measured respectively by utilizing the fitting WALA ridge plane (WP) which was fitted by the least square method and the occlusal plane (OP) as reference planes. SPSS (version 26) was used to analyze the data. RESULTS: In all criteria evaluated, RS decreased steadily from the crown to the root (P < 0.05), the minimum was at the root tip. From PG-A classification, PG-B classification to PG-C classification and from PG-I classification, PG-II classification to PG-III classification, RS both appeared a diminishing tendency (P < 0.05). As the degree of mesial tilt decreased, RS appeared an increasing trend (P < 0.05). RS in classification criteria of buccolingual angle had no statistical difference (P > 0.05). CONCLUSIONS: RS was associated with positional classifications of the M3. In the clinic, RS can be evaluated by watching the Pell&Gregory classification and mesial angle of M3.

Effects of different designs of orthodontic clear aligners on the maxillary central incisors in the tooth extraction cases: a biomechanical study.

BACKGROUND: Controlling the 3D movement of central incisors during tooth extraction cases with clear aligners is important but challenging in invisible orthodontic treatment. This study aimed to explore the biomechanical effects of central incisors in tooth extraction cases with clear aligners under different power ridge design schemes and propose appropriate advice for orthodontic clinic. METHODS: A series of Finite Element models was constructed to simulate anterior teeth retraction or no retraction with different power ridge designs. These models all consisted of maxillary dentition with extracted first premolars, alveolar bone, periodontal ligaments and clear aligner. And the biomechanical effects were analysed and compared in each model. RESULTS: For the model of anterior teeth retraction without power ridge and for the model of anterior teeth no retraction with a single power ridge, the central incisors exhibited crown lingual inclination and relative extrusion. For the model of anterior teeth no retraction with double power ridges, the central incisors tended to have crown labial inclination and relative intrusion. For the model of anterior tooth retraction with double power ridges, the central incisors exhibited a similar trend to the first kind of model, but as the depth of the power ridge increased, there was a gradual decrease in crown retraction value and an increase in crown extrusion value. The simulated results showed that von-Mises stress concentration was observed in the cervical and apical regions of the periodontal ligaments of the central incisors. The clear aligner connection areas of adjacent teeth and power ridge areas also exhibited von-Mises stress concentration and the addition of power ridge caused the clear aligner to spread out on the labial and lingual sides. CONCLUSIONS: The central incisors are prone to losing torque and extruding in tooth extraction cases. Double power ridges have a certain root torque effect when there are no auxiliary designs, but they still cannot rescue tooth inclination during tooth retraction period. For tooth translation, it may be a better clinical procedure to change the one-step aligner design to two-step process: tilting retraction and root control.

Notch/NICD/RBP-J signaling axis regulates M1 polarization of macrophages mediated by advanced glycation end products.

Advanced glycation end products (AGEs) aggregation and macrophages polarization are identified as the main factors contributing to bone diseases caused by aging or diabetes, such as senile or diabetic osteoporosis. Here, we aimed to elucidate the involvement and potential mechanism of AGEs in macrophages polarization and osteoclastogenesis. Firstly, AGEs-treated RAW264.7 macrophages were observed to up-regulate the release of nitric oxide (NO), the expression of M1-associated genes and the surface antigen marker CD86. The detection of osteoclast-related markers and TRAP staining revealed that the osteoclastogenic ability of M1 macrophages was markedly enhanced by AGEs. Further, AGEs were found to effectively activate the transduction of Notch signaling pathway and promote the nuclear translocation of NICD1. In addition, with the signals transduction of Notch pathway blocked by γ-secretase inhibitor DAPT and siRNA targeting silencing RBP-J, AGEs-induced M1 polarization was significantly mitigated. Collectively, we defined a critical role for AGEs in inducing M1 polarization and osteoclastogenesis of macrophages, and further identified Notch/NICD/RBP-J signaling axis as an essential mechanism regulating AGEs-mediated M1 polarization.

Abnormal brain functional and structural connectivity between the left supplementary motor area and inferior frontal gyrus in moyamoya disease.

BACKGROUND: Disruption of brain functional connectivity has been detected after stroke, but whether it also occurs in moyamoya disease (MMD) is unknown. Impaired functional connectivity is always correlated with abnormal white matter fibers. Herein, we used multimodal imaging techniques to explore the changes in brain functional and structural connectivity in MMD patients. METHODS: We collected structural images, resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging for each subject. Cognitive functions of MMD patients were evaluated using the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Trail Making Test parts A and B (TMT-A/-B). We calculated the functional connectivity for every paired region using 90 regions of interest from the Anatomical Automatic Labeling Atlas and then determined the differences between MMD patients and HCs. We extracted the functional connectivity of paired brain regions with significant differences between the two groups. Correlation analyses were then performed between the functional connectivity and variable cognitive functions. To explore whether the impaired functional connectivity and cognitive performances were attributed to the destruction of white matter fibers, we further analyzed fiber integrity using tractography between paired regions that were correlated with cognition. RESULTS: There was lower functional connectivity in MMD patients as compared to HCs between the bilateral inferior frontal gyrus, between the bilateral supramarginal gyrus, between the left supplementary motor area (SMA) and the left orbital part of the inferior frontal gyrus (IFGorb), and between the left SMA and the left middle temporal gyrus (P < 0.01, FDR corrected). The decreased functional connectivity between the left SMA and the left IFGorb was significantly correlated with the MMSE (r = 0.52, P = 0.024), MoCA (r = 0.60, P = 0.006), and TMT-B (r = -0.54, P = 0.048) in MMD patients. White matter fibers were also injured between the SMA and IFGorb in the left hemisphere and were positively correlated with reduced functional connectivity. CONCLUSIONS: Brain functional and structural connectivity between the supplementary motor area and inferior frontal gyrus in the left hemisphere are damaged in MMD. These findings could be useful in the evaluation of disease progression and prognosis of MMD.

Erratum: Co-culture with Endothelial Progenitor Cells promotes the Osteogenesis of Bone Mesenchymal Stem Cells via the VEGF-YAP axis in high-glucose environments: Erratum.

[This corrects the article DOI: 10.7150/ijms.52316.].

Improved lip esthetics in patients with skeletal Class III malocclusion and facial asymmetry after isolated mandibular orthognathic surgery.

INTRODUCTION: Asymmetry of the lips severely affects facial esthetics and is often one of the chief complaints of orthognathic patients, especially those with Class III malocclusion. The objectives of this study were to investigate the changes in lip symmetry in patients with mandibular prognathism and deviation and the relationships between jaw hard tissue and lip soft-tissue changes. METHODS: Three-dimensional facial scan and cone-beam computed tomography scan data of 30 orthodontic-orthognathic patients treated with bilateral sagittal split ramus osteotomy were combined to conduct the research. Paired-sample t test and Pearson correlation coefficient were applied to compare the differences in the same variable before and after the orthognathic surgery and the potential correlations between the changes in hard and soft variables. To explore the important hard tissue variables influencing the lip soft-tissue changes, linear regression analysis was performed. RESULTS: Although there was significant upper lip asymmetry presurgery, the upper lip asymmetry was corrected postsurgery. Surgical correction of the mandibular deviation was also accompanied by lengthening of the bilateral philtrum crests. Improvement in lip asymmetry and lengthening of the philtrum crests were primarily related to the transverse correction of the mandible rather than sagittal changes. The corresponding prediction formulas were established. CONCLUSIONS: The isolated mandibular bilateral sagittal split ramus osteotomy surgery can substantially improve the upper and lower lip asymmetry in patients with mandibular prognathism and deviation, but one should be wary of the unesthetic effects associated with lengthening of the philtrum crests.

Effects of mouth breathing on maxillofacial and airway development in children and adolescents with different cervical vertebral maturation stages: a cross-sectional study.

BACKGROUND: To examine the influence of mouth breathing on maxillofacial and airway development in children and adolescents with different cervical vertebral maturation stages. METHODS: Lateral cephalometric radiograph of a total of 120 children and adolescents, 64 girls and 56 boys (7-15 years old), diagnosed with mouth breathing were examined. Maxillofacial hard tissue, soft tissue and airway measurements were obtained using both manual and digital techniques. Independent samples t-test was performed to compare the difference between the measured indexes and the standard values. RESULTS: As for maxillofacial hard tissue, SNB (CS1-CS5), GoGn (CS1-CS5), ArGoNa (CS1-CS5), ArGo (CS1-CS2) and SNA (CS1-CS2) in mouth breathing children and adolescents were below the standard values (P < 0.05). NGoMe (CS1-CS5), SN-MP (CS1-CS4), SN-PP (CS1-CS4), PP-MP (CS1-CS3) and SN-GoGn (CS1-CS2) in mouth breathing children and adolescents were above the standard values (P < 0.05). As for maxillofacial soft tissue measurements, H angle (CS1-CS5), lower lip length (CS1-CS5), upper lip protrusion (CS1-CS5), upper lip length (CS1-CS4), lower lip protrusion (CS1-CS3), surface Angle (CS2-CS3) and nasolabial angle (CS2) in mouth breathing children and adolescents were above the standard values with statistically significance (P < 0.05). As for airway measurements, PAS (CS1, CS2, CS5) in mouth breathing children and adolescents was above the standard value with statistical significance (P < 0.05). CONCLUSIONS: Mouth breathing had a real effect on maxillofacial and airway development, which differed among mouth breathing children and adolescents with different cervical vertebral maturation.

Reliability of cone beam CT for morphometry of nasolabial soft tissue in patients with skeletal class III malocclusion: A qualitative and quantitative analysis.

OBJECTIVE: To assess reliability of cone-beam CT (CBCT) for nasolabial soft tissue measurements in patients with skeletal class III malocclusion based on 3-dimensional (3D) facial scanner results. METHODS: CBCT and 3D facial scan images of 20 orthognathic patients are used in this study. Eleven soft tissue landmarks and 15 linear and angular measurements are identified and performed. For qualitative evaluation, Shapiro-Wilk test and Bland-Altman plots are applied to analyze the equivalence of the measurements derived from these two kinds of images. To quantify specific deviation of CBCT measurements from facial scanner, the latter is set as a benchmark, and mean absolute difference (MAD) and relative error magnitude (REM) for each variable are also calculated. RESULTS: Statistically significant differences are observed in regions of nasal base and lower lip vermilion between two methods. MAD value for all length measurements are less than 2 mm and for angular variables < 8°. The average MAD and REM for length measurements are 0.94 mm and 5.64%, and for angular measurements are 2.27° and 3.78%, respectively. CONCLUSIONS: The soft tissue results measured by CBCT show relatively good reliability and can be used for 3D measurement of soft tissue in the nasolabial region clinically.

[Microbial Diversity and Community Analysis of Dental Plaques in Orthodontic Patients Wearing Invisible Appliances and Fixed Appliances].

Objective: To explore the microbial diversity and community structure of dental plaques in orthodontic patients with invisible appliances and fixed appliances and to study the differences. Methods: Ten orthodontic patients wearing invisible appliances (I) and ten wearing fixed appliances (F) were recruited. Dental plaques were collected from both buccal (B) and lingual (L) sides. Based on 16S rDNA, 40 dental plaque samples were analyzed after Illumina sequencing. Results: The microbial diversity, abundance and evenness of the FB group were significantly higher than those of the IB and IL groups (P<0.05), while the FL group showed substantial individual differences. The community structures were generally similar among the four groups, but significant differences in the relative abundance of some bacteria were found. The IB group showed higher abundances of Actinomycetes and Rosella (P<0.05), which were considered to be involved in dental caries and periodontal diseases. Some key communities showing significant differences were significantly enriched in the FB group, including Coprobacillus, Bifidobacterium, Enterobacterium, Lactobacillus, etc.. Conclusion: Dental plaques in patients wearing invisible appliances and fixed appliances showed significantly different microbial abundance, diversity and composition, which may be involved in orthodontic complications such as dental caries and periodontal diseases. Orthodontic patients need strengthened measures for oral hygiene maintenance, no matter what kind of appliances they wear.

Co-culture with Endothelial Progenitor Cells promotes the Osteogenesis of Bone Mesenchymal Stem Cells via the VEGF-YAP axis in high-glucose environments.

Patients with type 2 diabetes mellitus (T2DM) have a high risk of fracture and experience poor bone healing. In recent years, bone mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs) have become the most commonly used cells in cell therapy and tissue engineering. In this study, we found that high glucose levels had a negative effect on the differentiation of BMSCs and EPCs. Considering that EPCs-BMSCs sheets can provide endothelial cells and osteoblastic cells, we transplanted cell sheets into T2DM rats with bilateral skull defects. The outcomes of the in vivo study revealed that EPCs-BMSCs sheets promoted ossification, which was verified by micro-CT and immunohistochemistry (IHC) analyses. Furthermore, we detected the VEGF content in the culture supernatant using an enzyme-linked immunosorbent assay (ELISA). The results showed that the BMSCs co-cultured with EPCs presented a higher level of VEGF than other cells. To assess the differentiation and migration of BMSCs exposed to VEGF, ALP staining, scratch assay and qRT-PCR analysis were performed. In addition, we used immunofluorescence and western blotting analysis to further explore the related mechanisms. The results showed that cells cultured with VEGF had a stronger actin cytoskeleton and a greater amount of nuclear and total YAP than cells cultured without VEGF. Taken together, our results indicate that co-culture with EPCs could promote the osteogenesis of BMSCs partially via VEGF. Furthermore, YAP and F-actin play important roles in this process.

Three-dimensional analysis of lip soft tissue changes and related jaw changes in patients with skeletal class III malocclusion and facial asymmetry.

OBJECTIVE: To investigate three-dimensional soft tissue changes of lips and related jaw changes in patients with skeletal class III malocclusion and facial asymmetry using cone-beam computerized tomography (CBCT). METHOD: This study included 46 CBCT scans of patients with aforementioned character before (T1) and 6-12 months after orthognathic surgery (T2). Subjects were divided into 2 groups according to two types of orthognathic surgery namely, the one-jaw surgery group who underwent bilateral sagittal splint ramus osteotomy (BSSRO) and the two-jaw surgery group who underwent Le Fort I osteotomy and BSSRO. Mimics 19.0 software are used for model reconstruction, landmark location and three-dimensional cephalometric analysis. Descriptive statistics and correlation analyses are used to investigate jaw hard tissue and lip soft tissue changes. RESULTS: In one-jaw group, the mandible shows changes in contour and position (p < 0.05), and the surgery causes changes of lip structure on the deviated side. While in two-jaw group, jaws only show changes in spatial position, and surgery changes contour of bilateral lips and nasolabial angle (p < 0.05). At the same time, lip symmetry increases significantly in both groups postoperatively. CONCLUSIONS: Orthognathic surgery can improve lip aesthetics in patients with skeletal class III malocclusion and facial asymmetry. However, changes induced by two surgical approaches are different. Surgeons should have a clear acquaintance with this difference to deal with different situations.

Effects of mouth breathing on facial skeletal development in children: a systematic review and meta-analysis.

BACKGROUND: Mouth breathing is closely related to the facial skeletal development and malocclusion. The purpose of this systematic review and meta-analysis was to assess the effect of mouth breathing on facial skeletal development and malocclusion in children. METHODS: An electronic search in PubMed, the Cochrane Library, Medline, Web of Science, EMBASE and Sigle through February 23rd, 2020, was conducted. Inclusion criteria were children under 18 years of age with maxillofacial deformities due to mouth breathing. The risk of bias in nonrandomized studies of interventions (ROBINS-I) tool for controlled clinical trials. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used for the quality assessment. The included indicators were SNA, SNB, ANB, SN-OP, SN-PP, PP-MP, SNGoGn, MP-H, 1-NA, 1. NA, 1. NB, 1-NB, Overjet, Overbite, SPAS, PAS, and C3-H. Data concerning the mean difference in mesial molar movement and extent of canine retraction were extracted for statistical analysis. The mean differences and 95% confidence intervals were analyzed for continuous data. Review Manager 5.3, was used to synthesize various parameters associated with the impact of mouth breathing on facial skeletal development and malocclusion. RESULTS: Following full-text evaluations for eligibility, 10 studies were included in the final quantitative synthesis. In Sagittal direction, SNA (MD: - 1.63, P < 0.0001), SNB (MD: - 1.96, P < 0.0001) in mouth-breathing children was lower than that in nasal-breathing children. ANB (MD: 0.90, P < 0.0001), 1. NA (MD: 1.96, P = 0.009), 1-NA (MD: 0.66, P = 0.004), and 1-NB (MD: 1.03, P < 0.0001) showed higher values in children with mouth breathing. In vertical direction, SN-PP (MD: 0.68, P = 0.0050), SN-OP (MD: 3.05, P < 0.0001), PP-MP (MD: 4.92, P < 0.0001) and SNGoGn (MD: 4.10, P < 0.0001) were higher in mouth-breathing individuals. In airway, SPAS (MD: - 3.48, P = 0.0009), PAS (MD: - 2.11, P < 0.0001), and C3-H (MD: - 1.34, P < 0.0001) were lower in mouth breathing group. CONCLUSIONS: The results showed that the mandible and maxilla rotated backward and downward, and the occlusal plane was steep. In addition, mouth breathing presented a tendency of labial inclination of the upper anterior teeth. Airway stenosis was common in mouth-breathing children. Trial registration crd-register@york.ac.uk, registration number CRD42019129198.

[PVT1 Promoted the Proliferation and Migration Ability of BMSCs in Glioma C6 Microenvironment].

OBJECTIVE: To investigate the changes in the proliferation and migration ability of bone marrow mesenchymal stem cells (BMSCs) after indirect co-culturing with glioma C6 cells, and to examine the role of plasmacytoma variant translocation 1 gene ( PVT1), a long non-coding RNA (lncRNA), in these changes. METHODS: After separation, cultivation and identification of BMSCs, BMSCs of good growth condition were picked out and indirectly co-cultured with glioma C6 cells in Transwell chambers. These cells are henceforth referred to as the co-culture group. Normal BMSCs cultured separately were the control group. CCK-8 and soft agar colony formation assay were used to examine the proliferation ability of the two groups of cells. Flow cytometry was used to examine the cell cycle. Wound healing assay and Transwell assay were used to explore the migration ability of the cells. Quantitative real-time PCR (qRT-PCR) was used to examine the genetic expression level of PVT1 in the two groups. The above-mentioned tests were repeated after the co-cultured BMSCs were transfected with si- PVT1 (si- PVT1 group) and si-NC (si-NC group). In addition, qRT-PCR was done to evaluate the expression of CyclinD1, a cell cycle protein gene, and matrix metalloproteinases 2 and 9 ( MMP2 and MMP9), the migration-related genes in the si- PVT1 and si-NC transfected co-cultured BMSCs. RESULTS: The BMSCs used in the present study possess the capability of osteogeneic and adipogenic differentiation. Compared with the control group, the co-cultured BMSCs had smaller size, disorderly arrangement and the lack of intercellular contact inhibition. The proliferation and migration ability was significantly enhanced, the proportions of S and G 2 phase cells greatly increased and the expression level of PVT1 was significantly up-regulated ( P<0.05) in the co-cultured group in comparison with those of the control group. When compared with the si-NC group, the si- PVT1 group showed inhibited proliferation and migration ability of the co-cultured BMSCs; the percentage of G 1 phase cells increased, while that of S phase decreased; the expression of PVT1, CyclinD1, MMP2 and MMP9 mRNA also decreased ( P<0.05) in the si- PVT1 group. CONCLUSION: The enhanced proliferation and migration ability of BMSCs in the glioma C6 microenvironment may be associated with the up-regulated expression of PVT1 .