Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.

Objective:To explore the effect of ubiquitin-specific protease 42(USP42)on osteogenic differentiation of human adipose-derived stem cells(hASCs)in vivo and in vitro.Methods:A combina-tion of experiments was carried out with genetic depletion of USP42 using a lentiviral strategy.Alkaline phosphatase(ALP)staining and quantification,alizarin red S(ARS)staining and quantification were used to determine the osteogenic differentiation ability of hASCs under osteogenic induction between the experimental group(knockdown group and overexpression group)and the control group.Quantitative re-verse transcription PCR(qRT-PCR)was used to detect the expression levels of osteogenesis related genes in the experimental group and control group,and Western blotting was used to detect the expression levels of osteogenesis related proteins in the experimental group and control group.Nude mice ectopic im-plantation experiment was used to evaluate the effect of USP42 on the osteogenic differentiation of hASCs in vivo.Results:The mRNA and protein expressions of USP42 in knockdown group were significantly lower than those in control group,and those in overexpression group were significantly higher than those in control group.After 7 days of osteogenic induction,the ALP activity in the knockdown group was sig-nificantly higher than that in the control group,and ALP activity in overexpression group was significantly lower than that in control group.After 14 days of osteogenic induction,ARS staining was significantly deeper in the knockdown group than in the control group,and significantly lighter in overexpression group than in the control group.The results of qRT-PCR showed that the mRNA expression levels of ALP,os-terix(OSX)and collagen type Ⅰ(COL Ⅰ)in the knockdown group were significantly higher than those in the control group after 14 days of osteogenic induction,and those in overexpression group were signifi-cantly lower than those in control group.The results of Western blotting showed that the expression levels of runt-related transcription factor 2(RUNX2),OSX and COL Ⅰ in the knockout group were significant-ly higher than those in the control group at 14 days after osteogenic induction,while the expression levels of RUNX2,OSX and COL Ⅰ in the overexpression group were significantly lower than those in the control group.Hematoxylin-eosin staining of subcutaneous grafts in nude mice showed that the percentage of osteoid area in the knockdown group was significantly higher than that in the control group.Conclusion:Knockdown of USP42 can significantly promote the osteogenic differentiation of hASCs in vitro and in vi-vo,and overexpression of USP42 significantly inhibits in vivo osteogenic differentiation of hASCs,and USP42 can provide a potential therapeutic target for bone tissue engineering.

Objective:To explore the effects of different polymers on in vitro biomimetic mineralization of small intestinal submucosa(SIS)scaffolds,and to evaluate the physicochemical properties and bio-compatibility of the SIS scaffolds.Methods:The SIS scaffolds prepared by freeze-drying method were im-mersed in simulated body fluid(SBF),mineralized liquid containing polyacrylic acid(PAA)and mine-ralized liquid containing PAA and polyaspartic acid(PASP).After two weeks in the mineralized solu-tion,the liquid was changed every other day.SBF@SIS,PAA@SIS,PAA/PASP@SIS scaffolds were ob-tained.The SIS scaffolds were used as control group to evaluate their physicochemical properties and bio-compatibility.We observed the bulk morphology of the scaffolds in each group,analyzed the microscopic morphology by environment scanning electron microscopy and determined the porosity and pore size.We also analyzed the surface elements by energy dispersive X-ray spectroscopy(EDX),analyzed the struc-ture of functional groups by Flourier transformed infrared spectroscopy(FTIR),detected the water ab-sorption rate by using specific gravity method,and evaluated the compression strength by universal me-chanical testing machine.The pro-cell proliferation effect of each group of scaffolds were evaluated by CCK-8 cell proliferation method.Results:Under scanning electron microscopy,the scaffolds of each group showed a three-dimensional porous structure with suitable pore size and porosity,and crystal was observed in all the mineralized scaffolds of each group,in which the crystal deposition of PAA/PASP@SIS scaffolds was more regular.At the same time,the collagen fibers could be seen to thicken.EDX analysis showed that the characteristic peaks of Ca and P were found in the three groups of mineralized scaffolds,and the highest peaks were found in the PAA/PASP@SIS scaffolds.FTIR analysis proved that all the three groups of mineralized scaffolds were able to combine hydroxyapatite with SIS.All the scaf-folds had good hydrophilicity.The compressive strength of the mineralized scaffold in the three groups was higher than that in the control group,and the best compressive strength was found in PAA/PASP@SIS scaffold.The scaffolds of all the groups could effectively adsorb proteins,and PAA/PASP@SIS group had the best adsorption capacity.In the CCK-8 cell proliferation experiment,the PAA/PASP@SIS scaffold showed the best ability to promote cell proliferation with the largest number of living cells observed.Con-clusion:Compared with other mineralized scaffolds,PAA/PASP@SIS scaffolds prepared by mineralized solution containing both PAA and PASP have better physicochemical properties and biocompatibility and have potential applications in bone tissue engineering.

Objective:To analyze the histopathological characteristics of peri-implant soft tissue in re-constructed jaws and the changes after keratinized mucosa augmentation(KM A)with free gingival graft(FGG).Methods:Twenty patients were enrolled in this study.Five patients of them,who were perio-dontal and systemic healthy and referred for crown lengthening before restoration with healthy keratinized gingiva collected were enrolled as healthy controls.15 patients of them were with fibula or iliac bone flaps jaw reconstruction(10 with fibula flap and 5 with iliac flap),who were referred to FGG and implant exposures before restoration.Soft tissue was collected before FGG in reconstructed jaws,and in 5 patients(3 with fibula flap and 2 with iliac flap)8 weeks after FGG if a second surgery was conducted.Histologi-cal analysis with hematoxylin-eosin stain and immunological analysis to interlukin-1(IL-1),interlukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were performed.Results:Thickness from the bottom of stratum basale to the top of stratum granulosum and thickness of keratinized layer in reconstructed jaws were significantly lower compared with that of natural healthy keratinized gingiva[0.27(0.20,0.30)mmvs.0.36(0.35,0.47)mm,P＜0.05;16.49(14.90,23.37)μm vs.26.37(24.12,31.53)μm,P＜0.05].In the reconstructed area,thickness from the bottom of stratum basale to the top of stra-tum granulosum increased after KMA with FGG[0.19(0.16,0.25)mm vs.0.38(0.25,0.39)mm,P=0.059]and the thickness of keratinized layer significantly increased after KMA with FGG[16.42(14.16,22.35)μm vs.28.57(27.16,29.14)μm,P＜0.05],which was similar to that in the con-trol group.Furthermore,the number of positive cells of IL-1,IL-6 and TNF-α significantly increased after KMA[0.67(0.17,8.93)vs.11.00(9.16,18.00);13.00(8.50,14.14)vs.21.89(15.00,28.12);0.22(0.04,0.63)vs.2.83(1.68,5.00),respectively,P＜0.05]as well as the average optical density value[0.15(0.14,0.17)vs.0.18(0.17,0.21);0.28(0.26,0.33)vs.0.36(0.33,0.37);0.23(0.22,0.29)vs.0.30(0.28,0.42),respectively,P＜0.05],which was similar to that in the healthy keratinized gingiva.Conclusion:The lack of rete pegs and inflammato-ry factors were common in soft tissue with jaw reconstruction.FGG can improve the quality of the epithe-lium and may improve the stability of the mucosa around implants.

Objective:To detect key genes of local glucocorticoid therapy in oral lichen planus(OLP)through transcriptome sequencing.Methods:The study prospectively enrolled 28 symptomatic patients who visitied Department of Oral Mucosa,Peking University Hospital of Stomatology from November 2019 to March 2023.Topical inunction of 0.1 g/L of dexamethasone was applied for 1 min,3 times daily for 4 weeks.The patients'signs and pain symptoms were recorded and they were classified as effective group and ineffective group according to the treatment outcome.Their mucosa samples were collected before treatment.After isolating total RNA,transcriptome sequencing was performed.The gene expression data obtained by sequencing were analyzed differently using the DESeq2 package in R software,and the Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis was performed on the basis of the hypergeometric distribution algorithm to describe the biological function of differentially expressed genes(DEGs),accordingly detecting sensitivity related molecular affecting therapeutic effect of dexamethasone.Results:After 4 weeks treatment by topical dexamethasone,13 cases of the 28 OLP pa-tients responding well with the sign score reducing from 7.0(4.5,9.0)to 5.0(3.0,6.3),pain score decreasing from 5.0(2.0,5.5)to 2.0(0.0,3.5),oral health impact profile lessening from 5.0(3.5,9.0)to 1.0(0.0,5.0)significantly(P＜0.01)were classified as effective group and 15 cases with poor response to the drug were sorted as ineffective group.There were no significant differences of demographic and baseline levels of clinical features,especially disease severity between these two groups.A total of 499 DEGs including 274 upregulated and 225 downregulated genes were identified between ef-fective group and ineffective group.KEGG enrichment analysis showed that upregulated genes in effective group compared with ineffective group including CLDN8,CTNNA3,MYL2 and MYLPF were associated with leukocyte transendothelial migration,while downregulated genes were significantly enriched in tumor necrosis factor(TNF),interleukin-17(IL-17),nuclear factor kappa B(NF-κB)signaling pathways,and cortisol synthesis and secretory.Conclusion:High expressions of CLDN8,CTNNA3,MYL2 and MYLPF genes in patients with oral lichen planus have a good clinical response to topical dexamethasone,while patients with high expression genes of inflammation pathway such as TNF,IL-17,NF-κB and corti-sol synthesis and secretion received poor effect.

Objective:To find out factors influencing the compliance of supportive treatment of patients with periodontitis who have received implant restoration therapy.Methods:Patients who had completed periodontal and implant restoration treatment for more than 5 years in Department of Periodontology,Pe-king University Hospital of Stomatology were subjected to inclusion between March 2022 and August 2023.A questionnaire was compiled to gather the information including patients'basic information(gen-der,age,and educational background etc.),smoking habits,general health conditions,oral hygiene habits,willingness to undertake periodontal and dental implant supportive treatment,actual fact on sup-portive treatment recorded in medical records,whether medical advices were correctly remembered,and reasons affected them to implement supportive therapy.The questionnaires were handed out to the above patients and filled during the process of follow-up treatment.Chi-square test,univariate and multivariate analysis of Logistic regression were employed to explore the correlations of these factors and the patients'compliance.Results:In the study,92 patients and questionnaires were collected and analyzed.The re-sults indicated that oral hygiene habits and whether medical advices were correctly remembered had sig-nificant correlation with compliance(P＜0.05).Time constraint(47.0％)and difficulty in appointment registration(24.8％)were the top 2 reasons obstructed them to undertake supportive treatment.Al-though the vast majority of the patients indicated willingness to perform follow-ups,55.4％of them wouldn't come back until the dentist called them back.The results of our study also indicated that the patients placed significantly less importance on the health of natural teeth than implants.Conclusion:In order to improve the compliance of supportive treatment,we suggest that dentists should put more empha-sis on oral hygiene instruction,and knowledge regarding periodontitis should also be added as part of pa-tient education contents.In the early stages of treatment,the patient should develop the habit of regular follow-up checks,More attention and patience should be given to elderly patients and those with lower level of education;use language that is easy to understand and printed medical instructions to help them remember.Patients can memorize better from refined doctors'advice,reinforcing care knowledge and refining medical advices can promote better follow-up treatment results.Motivating patients based on their characteristics is critical to improving compliance.

Objective:To investigate the differences and similarities of parameters associated with ane-mia of inflammation between patients with stage Ⅲ periodontitis and periodontally healthy volunteers,and to explore the influence of periodontal initial therapy on those indicators.Methods:Patients with stageⅢ periodontitis and periodontally healthy volunteers seeking periodontal treatment or prophylaxis at De-partment of Periodontology,Peking University School and Hospital of Stomatology from February 2020 to February 2023 were enrolled.Their demographic characteristics,periodontal parameters(including pro-bing depth,clinical attachment loss,bleeding index),and fasting blood were gathered before periodontal initial therapy.Three months after periodontal initial therapy,the periodontal parameters of the patients with stage Ⅲ periodontitis were re-evaluated and their fasting blood was collected again.Blood routine examinations(including white blood cells,red blood cells,hemoglobin,packed cell volume,mean cor-puscular volume of erythrocytes,and mean corpuscular hemoglobin concentration)were performed.And ferritin,hepcidin,erythropoietin(EPO)were detected with enzyme-linked immunosorbent assay(ELISA).All data analysis was done with SPSS 21.0,independent sample t test,paired t test,and analysis of co-variance were used for comparison between the groups.Results:A total of 25 patients with stage Ⅲperiodontitis and 25 periodontally healthy volunteers were included in this study.The patients with stageⅢ periodontitis were significantly older than those in periodontally healthy status[(36.72±7.64)years vs.(31.44±7.52)years,P=0.017].The patients with stage Ⅲ periodontitis showed lower serum he-moglobin[(134.92±12.71)g/L vs.(146.52±12.51)g/L,P=0.002]and higher serum ferritin[(225.08±103.36)μg/L vs.(155.19±115.38)μg/L,P=0.029],EPO[(41.28±12.58)IU/L vs.(28.38±10.52)IU/L,P＜0.001],and hepcidin[(48.03±34.44)μg/L vs.(27.42±15.00)μg/L,P=0.009]compared with periodontally healthy volunteers.After adjusting the age with the co-variance analysis,these parameters(hemoglobin,ferritin,EPO,and hepcidin)showed the same trends as independent-sample t test with statistical significance.Three months after periodontal initial therapy,all the periodontal parameters showed statistically significant improvement.The serum hemoglobin raised[(146.05±15.48)g/L vs.(133.77±13.15)g/L,P＜0.001],while the serum ferritin[(128.52± 90.95)μg/Lvs.(221.22±102.15)μg/L,P＜0.001],EPO[(27.66±19.67)IU/L vs.(39.63± 12.48)IU/L,P=0.004],and hepcidin[(32.54±18.67)μg/L vs.(48.18±36.74)μg/L,P=0.033]decreased compared with baseline.Conclusion:Tendency of iron metabolism disorder and ane-mia of inflammation was observed in patients with stage Ⅲ periodontitis,which can be attenuated by periodontal initial therapy.

Objective:To investigate the clinical application effect of double-layer soft tissue(DLST)suture closure technique in patients with mandible medication-related osteonecrosis of the jaw(MRONJ)of early and medium stages resulted in application of anti-bone-resorptive drugs.Methods:Early to me-dium stage mandible MRONJ patients who underwent surgical treatment in the fourth ward of Peking Uni-versity School and Hospital of Stomatology from October 2021 to September 2022 were included.Clinical information of the patients were collected,including primary disease,concomitant disease,medication regimen(drug type,duration of medication),MRONJ stage,clinical symptoms,imaging manifestations,etc.During surgery,after using marginal mandibulae resection to remove the necrotic bone,the wound was closed using DLST closure technique.Regular post-operative follow-up was performed to evaluate the therapeutic effect and complications of the DLST technique,the pain score and functional status of the patiens were evaluated.Results:This study totally included 13 patients,12 women and 1 man,aged(66.69±13.14)years.Seven patients had osteoporosis,2 had lung cancer,3 had breast cancer and 1 had prostate cancer among their primary diseases;7 had no concomitant diseases,2 had diabetes melli-tus,2 had cardiovascular disease and 1 had dry syndrome.Intravenous zoledronic acid were used in 9 patients,the average duration was(37.7±20.0)months,and other drugs,such as letrozole tablets were taken in 7 patients at the same time;Denosumab injection was used in 3 patients for an average of(10.3±11.9)months;Alendronate sodium tablets were taken in 5 patients for an average of(55.20± 27.20)months,and prednisone acetate tablets or acarbose tablets were taken to varying degrees in 2 pa-tients.The average post-operative follow-up was 11.9 months(9 to 17 months),and all the 13 patients were cured without complications,such as pus overflow and so forth.The pre-operative score of Karnof-sky performance status(KPS)in the patients was 68.46±14.05,and the post-operative score was 82.31±15.36,and the difference was statistically significant(P＜0.05).The pre-operative score of visual analogue scale(VAS)in the patients was 5.77±0.73 and the post-operative score was 0.38±0.51,and the difference had statistical significance(P＜0.001).Conclusion:The double-layer soft tissue suture closure technique can achieve good clinical results in patients with MRONJ of the man-dible using anti-bone-resorptive drugs alone,and can provide clinical treatment ideas for MRONJ patients with more complicated drug use.

Objective:To establish and assess the precision of pre-surgical condyle position planning using mandibular movement trajectory data for orthognathic surgery.Methods:Skull data from large-field cone beam computed tomography(CBCT)and dental oral scan data were imported into IVSPlan 1.0.25 software for 3D reconstruction and fusion,creating 3D models of the maxilla and mandible.Trajectory da-ta of mandibular movement were collected using a mandibular motion recorder,and the data were inte-grated with the jaw models within the software.Subsequently,three-dimensional trajectories of the con-dyle were obtained through matrix transformations,rendering them visually accessible.A senior oral and maxillofacial surgeon with experience in both diagnosis and treatment of temporomandibular joint disease and orthognathic surgery selected the appropriate condyle position using the condyle movement trajectory interface.During surgical design,the mobile mandibular proximal segment was positioned accordingly.Routine orthognathic surgical planning was completed by determining the location of the mandibular distal segment,which was based on occlusal relationships with maxilla and facial aesthetics.A virtual mandible model was created by integrating data from the proximal and distal segment bone.Subsequently,a solid model was generated through rapid prototyping.The titanium plate was pre-shaped on the mandibular model,and the screw hole positions were determined to design a condylar positioning guide device.In accordance with the surgical plan,orthognathic surgery was performed,involving mandibular bilateral sagittal split ramus osteotomy(SSRO).The distal segment of the mandible was correctly aligned inter-maxillary,while the proximal bone segment was positioned using the condylar positioning guide device and the pre-shaped titanium plate.The accuracy of this procedure was assessed in a study involving 10 patients with skeletal class Ⅱ malocclusion.Preoperative condyle location planning and intraoperative po-sitioning were executed using the aforementioned techniques.CBCT data were collected both before the surgery and 2 weeks after the procedure,and the root mean square(RMS)distance between the preope-rative design position and the actual postoperative condyle position was analyzed.Results:The RMS of the condyle surface distance measured was(1.59±0.36)mm(95％CI:1.35-1.70 mm).This value was found to be significantly less than 2 mm threshold recommended by the expert consensus(P＜0.05).Conclusion:The mandibular trajectory may play a guiding role in determining the position of the mandibular proximal segment including the condyle in the orthognathic surgery.Through the use of a con-dylar positioning guide device and pre-shaped titanium plates,the condyle positioning can be personalized and customized with clinically acceptable accuracy.

Objective:To evaluate the postoperative denture restoration and denture function in pa-tients with mandibular defect reconstructed with vascularized free fibula flap.Methods:In the study,154 patients who underwent mandibular segment resection and used vascularized free fibula flap to repair mandibular defects due to inflammation,trauma and tumor from January 2015 to December 2020 were collected.These patients had common inclusion criteria which were stable occlusal relationship before operation,segmental defects of mandibular bone caused by lesions of mandible and adjacent parts(such as floor of mouth,tongue,cheek),free fibula flap used for repair and surviving after operation.Relevant data were reviewed and situation of denture restoration was followed up.A questionnaire related to den-ture functional evaluation had been proposed for those who had completed the denture rehabilitation.The evaluation index of denture restoration function was assigned by expert authority to obtain the denture function score.SPSS 18.0 software was used for statistical analysis of the basic information of the patients included in the study and the denture restoration of the patients.Results:The rate of postoperative den-ture restoration in the patients with mandibular defects repaired by free fibula flap was 17.5％,and the rate of postoperative denture restoration in the patients with benign mandibular tumors was 25.0％(18/72),which was significantly greater than that in the patients with malignant tumors 11.0％(9/82,P＜0.05).There was no significant difference in denture function score between the patients with condylar defect and those without condylar defect in denture repair rate and denture function score(P＞0.05).The functional score of implant denture was significantly greater than that of removable denture(P＜0.05).According to Brown classification,the denture function score of the patients with the defect invo-lving the anterior mandibular region was significantly greater than that of the patients without the anterior mandibular region involved(P＜0.05).The poor oral conditions,such as less amount of remaining teeth,insufficient retention strength,large mobility of soft tissue in the surgical area,poor oral vestibular groove condition became the main reason of not receiving denture restoration(37.86％).Conclusion:The denture rehabilitation of mandibular defect reconstructed with vascularized free fibula flap is closely rela-ted to pathological properties and oral conditions.The clinical outcome of implant denture has been con-firmed effectively and it is a better choice for future denture restoration after mandibular reconstruction.