Recurrent aphthous ulcer (RAU) is one of the most common diseases of the oral mucosa. At present, no effective method is available for RAU treatment, especially for refractory RAU, which significantly affects patients’ oral health and quality of life. Research shows that combination with systemic diseases greatly increases the difficulty of curing refractory RAU, making conventional oral ulcer treatment harder to perform effectively. This is probably because dentists commonly only focus on handling oral ulcers but neglect to think about the etiology of oral ulcers from a holistic perspective. Thus, we summarized some conditions of refractory RAU accompanied by systemic diseases, including inflammatory bowel disease, iron deficiency anemia, diabetes mellitus, Behçet’s disease, Reiter’s syndrome, sprue syndrome, Sutton syndrome, and acquired immunodeficiency syndrome. We also outlined the treatment principles of these patients. To be specific, on the one hand, dentists should cooperate with the relevant specialists to treat the systemic diseases, while on the other hand they should take measures including topical/general use of medicine, local physical therapy, Traditional Chinese medicine treatment, and psychotherapy for RAU management. This paper aims to provide clinicians with a more comprehensive understanding of the diagnosis and treatment of refractory RAU, in order to make personalized treatment plans for patients and improve the clinical efficacy of refractory RAU.

Objective To explore the pathogenic genes in a Chinese family affected by nonsyndromic tooth agenesis so as to study the pathogenesis of oligodontia. Methods Hospital ethical approval and informed consent of the patients and family members were obtained. Clinical data of the proband and close family members were collected, peripheral venous blood was collected, and DNA was extracted. Gene sequencing was performed through whole-exome sequencing, and then the screened pathogenic genes were verified by Sanger sequencing. The three-dimensional structure of the mutant proteins was analyzed and compared with the wild-type using bioinformatics tools. Results The two patients with congenital majority tooth loss in this family were cousins, and there were no other patients with congenital majority tooth loss in the family. Besides congenital multiple tooth loss, the two patients had no obvious hair abnormalities, finger/toe abnormalities, sweating abnormalities or other abnormal manifestations of ectodermal tissue. We found a mutant gene that in this family by carrying out gene sequencing of the patients and their close family members. A novel EDA (ectodysplasin A) missense mutation c.983C>T (p. Pro328Leu) was identified, which changed the encoded amino acid from proline (Pro) to leucine (Leu). Analysis of the mutation site showed that the site was highly conserved, and three-dimensional structure modeling also found that it changed the structure of EDA. Conclusion A novel EDA missense variant (c.983C>T, p.Pro328Leu) was first identified in a Chinese family with nonsyndromic tooth agenesis, extending the mutation spectrum of the EDA gene.

Objective To find any differentially expressed circRNAs in oral leukoplakia (OLK) and oral lichen planus (OLP), to investigate the possible role of circRNAs in the pathogenesis of these two diseases. Methods This study obtained hospital ethical approval. High-throughput sequencing was used to detect differentially expressed circRNAs in OLK, OLP, oral squamous cell carcinoma and normal oral mucosal tissues. CircRNAs were verified by qRT-PCR, enzyme tolerance assays and Sanger sequencing. GO functional analysis and KEGG pathway analysis were performed to predict the functions of circRNAs in OLP. TargetScan and miRanda were applied to predict targeted miRNAs and mRNAs of circRNAs, and ceRNA networks were mapped. Results A total of 49 circRNAs were differentially expressed in OLK and OLP together, including 30 upregulated and 19 downregulated circRNAs. The five circRNAs confirmed with RT-qPCR, including circHLA-C, circRNF13, circTTN, circSEPN2 and circALDH3A2, were all abnormally expressed in OLK and OLP, among which circHLA-C was a key circRNA with trans splice sites, which was validated by expanding the sample size. ROC curve analysis showed that the area under the circHLA-C curve for predicting OLK was 0.955, and the area under the circHLA-C curve for predicting OLP was 0.988. GO functional analysis showed enrichment of many biological processes related to the immune process. The KEGG pathway with the highest enrichment score was "Natural killer cell mediated cytotoxicity". HLA-C was significantly enriched in these processes/pathways. CeRNA network analysis showed that circHLA-C interacted with a variety of miRNAs, such as hsa-miR-26a-5p, hsa-miR-129-5p, and hsa-miR-29a-3p. Conclusion Many circRNAs were differentially expressed in both OLK and OLP, circHLA-C being the most elevated. CircHLA-C is valuable for the early diagnosis of OLK and OLP and may serve as a potential biomarker for the diagnosis and prognosis of OLK and OLP.

Objective To study smile exposure in 20- to 30-year-olds with convex facial profiles and to explore the correlation between smile exposure and other aesthetic indicators, as well as psychological factors. Methods This study obtained ethical approval from the hospital. After they gave informed consent and portrait authorization, 80 young subjects aged 20-30 with convex facial profiles had their dynamic postural smile and spontaneous laughter recorded. The videos were imported into Photoshop CC software, key frames were selected, and the smile exposure was measured. The three-dimensional information of the subject's face in a resting state was obtained, the relevant aesthetic indicators were measured, and the satisfaction degree of their smile and laughter were evaluated. Correlation analysis was conducted for smile exposure and the relevant aesthetic indicators and subjective psychological evaluation. Results There were statistically significant differences in smile exposure, smile patterns, relevant aesthetic indicators and subjective psychological evaluation between males and females aged 20 to 30 (P<0.05). There was a large gap between males and females in the average opening degree when laughing, males having 5 times that of females, while the average gingival exposure height of the maxillary central incisor in males was approximately 1/2 of that in females. The average nasolabial angle of males (99.80° ± 7.96°) was larger than that of females (96.26° ± 7.31°) (P<0.05), while the average ratio of upper lip length to the length of the lower 1/3 of the face of males (33.73% ± 2.35%) was less than that of females (38.57% ± 2.76%) (P<0.05). The average psychological score of males (57.75±13.46) was higher than that of females (53.69±17.95) (P<0.05). The ratios of maxillary teeth and gingival exposure to oral fissure in the postural smile were positively correlated with the nasolabial angle. The oral fissure width in spontaneous laughter was negatively correlated with psychological score. Conclusion Convex-faced males and females aged 20 to 30 have different smile exposures and smile patterns. Males tend to smile more openly with a larger opening and less gingival exposure, while females tend to grin with a small opening and more gingival exposure. Smile exposure is positively correlated with nasolabial angle and negatively correlated with smile satisfaction.

Objective To explore the ideal sagittal position of the lower third of the face in high-angle patients with different forehead forms and to provide a reference for clinical treatment. Methods Informed consent and portrait authorization were obtained from all patients, and the study passed the ethical review of the unit. We categorized forehead forms into four types: straight, rounded, type I angular (angled at the middle third of the forehead) and type II angular (angled at the upper third of the forehead). Profiles of high-angle patients with different forehead forms were collected. The initial position was when the facial axis point (FA point) was positioned at the goal anterior-limit line (GALL). After being silhouetted, the lower third of the face was moved forward and backward by 1 mm, 2 mm, 3 mm, and 4 mm each, plus the initial silhouetted picture, to obtain 9 images for each patient. A survey was created with these lateral profile silhouettes, and the silhouette images were ranked by 30 orthodontists and 30 laypersons. Results There were significant differences in profile scores at different movement distances of the lower third of the face among high-angle patients with different forehead shapes (P<0.05). Overall, high-angle patients with straight or type II angular foreheads had higher scores when the lower third of the face did not move. For high-angle patients with a rounded forehead, orthodontists and laypersons gave the highest scores when the lower third of the face was moved backward by 2 mm and 4 mm, respectively. For high-angle patients with a type I angular forehead, orthodontists thought the scores of backward movement of 4 mm were the highest, and laypersons thought the scores of backward movement of 3 mm were the highest. No significant difference was found in scores between orthodontists and laypersons (P>0.05). Conclusion The forehead forms and the sagittal position of the lower third of the face will affect the face’s profile aesthetics. Patients with straight and type Ⅱ angular foreheads has the best profile when the FA point is located on the GALL line. For patients with rounded and type Ⅰ angular foreheads, a posterior location of the lower third of the face is more desirable than the initial position.

Objective To evaluate the clinical efficacy of positioning guide templates for maxillary wholly impacted supernumerary teeth to provide technological solutions for clinical applications. Methods After approval by the hospital ethics committee and informed consent given by the patients. Data from 136 patients with maxillary wholly impacted supernumerary teeth from January 2016 to April 2022 were analyzed retrospectively. The patients were divided into two groups according to the usage of the positioning guide template. The experimental group included patients using the positioning guide template (71 cases), and the control group did not use the positioning guide template (65 cases). The operation time and complications were statistically analyzed to evaluate the clinical efficacy after surgery. Results All operations were successfully completed. The average operation time in the experimental group was (21.5 ± 3.4) min, significantly shorter than that in the control group (27.2 ± 4.9) min. There were statistically significant differences between the experimental and control groups (t = 7.599, P<0.001). One week after the operation, there were no complications in the experimental group, and there were 2 cases of adjacent tooth injury and 3 cases of gingival numbness in the control group. Conclusion A digital positioning guide template can effectively shorten the time of maxillary wholly impacted supernumerary teeth extraction and is an effective means to assist clinical maxillary wholly impacted supernumerary teeth extraction.

Objective To explore the clinical application value of reflectance confocal microscopy(RCM) in the diagnosis of actinic cheilitis(AC). Methods After approval by the hospital ethics committee and informed consent given by the patients, from October 2020 to July 2022, 17 patients who were diagnosed with actinic cheilitis in the Ninth People's Hospital affiliated with Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The white keratotic lesions of the lips were scanned with reflectance confocal microscopy, and the image characteristics were summarized and analyzed, including epithelial hyperplasia/atrophy, hyperkeratosis, inflammatory cell infiltration, blood vessel dilatation, solar elastosis, atypical keratinocytes, widening of intercellular spaces, degeneration of basal cell layer, and pigmentation. We used the sample compliance rate to measure the correlation between RCM parameters and histopathological diagnostic criteria for AC and kappa concordance analysis to calculate the concordance between RCM and pathological diagnosis. Results Under RCM, the sample correct rates for epithelial hyperplasia/atrophy, hyperkeratosis, inflammatory cell infiltration, vasodilation, and solar elastosis were 76.5%, 100%, 100%, 64.7%, and 70.6%, the sample accuracy compared with pathological diagnosis was 82.4%, 47.1%, 94.1%, 88.2% and 76.5%, respectively. We also observed that 100%, 88.2%, 76.5%, and 88.2% of AC patients showed RCM features of atypical keratinocytes, widening of intercellular spaces, degeneration of the basal cell layer, and pigmentation, respectively. The kappa value of hyperkeratosis and inflammatory cell infiltration was 1. The kappa value of blood vessel dilatation was 0.645. Conclusion Reflectance confocal microscopy is noninvasive and versatile and has clinical application value in the diagnosis of actinic cheilitis.

Caries is a chronic infectious disease that occurs in the hard tissues of teeth. The interaction of oral microorganisms, host, food and time leads to the occurrence and progression of caries. Free sugar is an important food factor in the occurrence of dental caries. This paper reviews the research progress on the relationship between free sugar and caries in recent years, providing a reference for further clarifying the mechanism of the occurrence and progression of caries caused by free sugar and exploring the methods of caries prevention. The cariogenic mechanism of free sugar is multifaceted. Free sugar can not only be used by oral microorganisms in dental plaque biofilms to produce acid and synthesize intracellular and extracellular polysaccharides but also cause an imbalance in oral microecology and enhance gene expression related to the cariogenic toxicity of oral microorganisms. Based on the correlation between free sugar and caries, it is important to limit the intake amount and frequency of free sugar to prevent caries. This can be achieved mainly by formulating public health policies for reducing sugar, creating a low-sugar family environment with good eating habits, using sugar substitutes and using fluoride. There are few studies on the relationship between free sugar and oral microecology. More research is needed to better understand the effect of free sugar on oral microecology and its mechanism and to validate the caries-preventing effect of various sugar reduction measures. We believe such studies would open up new avenues for the effective prevention of caries.

Adiponectin, an adipocytokine secreted by adipocytes, has emerged as a potential treatment agent for type 2 diabetes. Adiponectin plays a variety of physiological roles in regulating glucolipid metabolism, oxidative stress, inflammatory responses and bone metabolism by binding to its receptors expressed on a variety of cells and tissues. Numerous studies have confirmed the strong association of adiponectin with type 2 diabetes-related periodontitis. Adiponectin can improve systemic insulin resistance by increasing insulin sensitivity and promoting insulin secretion. It improves the periodontal inflammatory response by inhibiting the expression of proinflammatory cytokines induced by Porphyromonas gingivalis lipopolysaccharide and promoting M2-type polarization of macrophages. In addition, adiponectin inhibits osteoclast differentiation and maturation through various pathways, such as Wnt/β-catenin and NF-κ, and promotes osteoblast differentiation to regulate bone metabolism, thus improving periodontal bone resorption and destruction. Therefore, adiponectin is expected to become a therapeutic target for type 2 diabetes-related periodontitis. Due to the physiological characteristics of adiponectin, its clinical application has been somewhat limited. This article reviews the latest research progress on adiponectin in type 2 diabetes-related periodontitis, aiming to elucidate the possible effects of adiponectin on type 2 diabetes-related periodontitis in terms of glycemic control, anti-inflammation and bone metabolism and to provide some opinions on the treatment of this disease and the development of relevant drugs.

The Porphyromonas gingivalis type IX secretion system (T9SS) is a recently discovered protein secretion system that is widely distributed in Bacillus cereus. The T9SS is structurally complex and powerful. More than 20 T9SS components have been verified, and more than 30 virulence factors can be secreted by Porphyromonas gingivalis alone, which contributes significant to the pathogenicity of Porphyromonas gingivalis. T9SS is a large protein complex spanning the inner cell membrane, periplasm, and outer cell membrane. Through the structural and functional connections among its components, it forms a sophisticated functional complex that includes power provision, energy transduction, inner and outer membrane translocation, outer membrane modification, and regulatory systems to recognize, translocate, shear, and modify cargo proteins and translocate bacterial intracellular cargo proteins to the cell surface. In recent years, with advancements in X-ray diffraction and in situ cryoelectron microscopy, the exploration of T9SS has evolved from the functional study of single components to the in situ structural study of multiprotein complexes. Still, the structural resolution of the protein still has shortcomings such as low resolution and an inability to capture dynamic functional structures. Future research directions should focus more on exploring how T9SS interacts and functions with cargo proteins. In this paper, we review the research progress on Porphyromonas gingivalis T9SS on X-ray diffraction and cryoelectron microscopy structure resolution in order to gain a deeper understanding of the transport mechanism of T9SS.

Oxidative stress is closely associated with the development of oral diseases such as caries, periodontitis and endodontitis. The accompanying oxidative stress during inflammation could aggravate tissue damage. However, numerous studies have shown that some dental materials, such as composite resins, bleach, drugs for root canal irrigation and dental implants, can give rise to abundant free radicals, which have adverse effects on peripheral tissues. Therefore, it is essential to supplement with extra antioxidants against free radicals. Plant-derived natural antioxidants have attracted great attention in biomedicine because of their excellent biocompatibility and easy access. This paper focused on the redox imbalance in the oral cavity and the application of natural antioxidants to oral therapy and their modification of dental materials. Current research shows that by constructing polyphenol-based metal organic nanoenzymes or adding vitamins and polyphenols to bionic hydrogels, the safety and utilization rate of antioxidants can be significantly improved. However, these polymer delivery systems have problems such as poor degradability, hepatotoxicity and nephrotoxicity, and the research is still in its infancy. In terms of material modification, it is crucial to choose the type and ratio of natural antioxidants and raw materials, as well as appropriate modification methods. A strong chemical bond between the antioxidant and the raw material may lead to the failure of antioxidant release from the modified composite, lowering the antioxidant activity. At the same time, the selection of polyphenols rich in pyrogallol functional groups can retain more free phenolic hydroxyl groups after chemical modification, which is conducive to greater antioxidant activity by the implant materials. Although research on natural antioxidants in oral therapy has made progress, there is a lack of data supporting clinical trials and long-term application effects, and further research is still needed.