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Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts

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International Journal of oral Science 2024年第2期16卷 349-358页

作者： Xinjia Cai Heyu Zhang Yanjin Wang Jianyun Zhang Tiejun Li Department of oral pathology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijingChina Central Laboratory Peking University School and Hospital of StomatologyBeijingChina Department of oral pathology Shanghai Stomatological Hospital&School of StomatologyFudan UniversityShanghaiChina Research Unit of Precision Pathologic Diagnosis in Tumors of the oral and Maxillofacial Regions Chinese Academy of Medical Sciences(2019RU034)BeijingChina

Odontogenic keratocyst(OKC)is a common jaw cyst with a high recurrence *** combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin ***,OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw *** of the different prognosis,differential diagnosis of several cysts can contribute to clinical *** collected 519 cases,comprising a total of 2157 hematoxylin and eosinstained images,to develop digital pathology-based artificial intelligence(AI)models for the diagnosis and prognosis of *** Inception_v3 neural network was utilized to train and test models developed from patch-level ***,whole slide imagelevel AI models were developed by integrating deep learning-generated pathology features with several machine learning *** AI models showed great performance in the diagnosis(AUC=0.935,95%CI:0.898–0.973)and prognosis(AUC=0.840,95%CI:0.751–0.930)of *** advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide ***,the study investigates the correlation between AI features generated by deep learning and pathological findings,highlighting the interpretative potential of AI models in the ***,we have developed the robust diagnostic and prognostic models for *** AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.

关键词： diagnosis pathology prognosis

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Cisplatin-based miRNA delivery strategy inspired by the circCPNE1/miR-330-3p pathway for oral squamous cell carcinoma

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2748-2760页

作者： Hua-yang Fan Ming-da Zhao Hong-jie Jiang Zhen-wei Yu Yu-jiang Fan Xin-hua Liang Ya-ling Tang Yong Sun State Key Laboratory of oral Diseases&National Center for Stomatology&National Clinical Research Center for oral Diseases&Department of oral and Maxillofacial Surgery West China Hospital of StomatologySichuan UniversityChengdu 610041China National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610065China State Key Laboratory of oral Diseases&National Center for Stomatology&National Clinical Research Center for oral Diseases&Department of oral pathology West China Hospital of StomatologySichuan UniversityChengdu 610041China

Circular RNAs(circRNAs)are ideal biomarkers of oral squamous cell carcinoma(OSCC)because of their highly stable closed-loop structure,and they can act as microRNA(miRNA)sponges to regulate OSCC *** analyzing clinical samples,we identified circCPNE1,a dysregulated circRNA in OSCC,and its expression level was negatively correlated with the clinical stage of OSCC ***-of-function assays revealed the tumor-suppressive effect of circCPNE1,which was then identified as a miR-330-3p ***-330-3p was recognized as a tumor promoter in multiple studies,consistent with our finding that it could promote the proliferation,migration,and invasion of OSCC *** results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC ***,we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p(a miRNA inhibitory analog)via electrostatic interactions to form PP@miR nanoparticles(NPs).Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination(2/5),which confirmed the critical role of miR-330-3p in OSCC *** findings provide a new perspective for the development of OSCC treatments.

关键词： oral squamous cell carcinoma CircRNA MiRNA sponge Antagomir MiRNA delivery Cisplatin-based nanoparticles Drug delivery systems Tumor elimination

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FUT8-mediated aberrant N-glycosylation of SEMA7A promotes head and neck squamous cell carcinoma progression

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International Journal of oral Science 2024年第2期16卷 333-348页

作者： Zhonglong Liu Xiaoyan Meng Yuxin Zhang Jingjing Sun Xiao Tang Zhiyuan Zhang Liu Liu Yue He Department of oral Maxillofacial&Head and Neck Oncology Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNational Clinical Research Center for Oral DiseaseShanghaiChina Department of oral Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghaiChina Department of oral pathology Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNational Clinical Research Center for Oral Disease ShanghaiShanghaiChina

SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor *** glycosylation has been intricately linked with immune escape and tumor ***7A is a highly glycosylated protein with five glycosylated *** underlying mechanisms of SEMA7A glycosylation and its contribution to immunosuppression and tumorigenesis are ***,we identify overexpression and aberrant N-glycosylation of SEMA7A in head and neck squamous cell carcinoma,and elucidate fucosyltransferase FUT8 catalyzes aberrant core fucosylation in SEMA7A at N-linked oligosaccharides(Asn 105,157,258,330,and 602)via a direct protein‒protein interaction.A glycosylated statue of SEMA7A is necessary for its intra-cellular trafficking from the cytoplasm to the *** EGF triggers SEMA7A N-glycosylation through increasing the binding affinity of SEMA7A toward FUT8,whereas TGF-β1 promotes abnormal glycosylation of SEMA7A via induction of epithelial–mesenchymal *** N-glycosylation of SEMA7A leads to the differentiation of CD8^(+)T cells along a trajectory toward an exhausted state,thus shaping an immunosuppressive microenvironment and being resistant immunogenic cell *** of SEMA7A significantly improves the clinical outcome of EGFR-targeted and anti-PD-L1-based ***,we also define RBM4,a splice regulator,as a downstream effector of glycosylated SEMA7A and a pivotal mediator of PD-L1 alternative *** findings suggest that targeting FUT8-SEMA7A axis might be a promising strategy for improving antitumor responses in head and neck squamous cell carcinoma patients.

关键词： aberrant squamous SEMA

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The spatial transcriptomic landscape of human gingiva in health and periodontitis

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Science China(Life Sciences) 2024年第4期67卷 720-732页

作者： Zongshan Shen Ran Zhang Yunjia Huang Jiayao Chen Mengjun Yu Chunhua Li Yong Zhang Lingling Chen Xin Huang Jichen Yang Zhengmei Lin Songlin Wang Bin Cheng Hospital of Stomatology Guangdong Provincial Key Laboratory of StomatologyGuanghua School of StomatologySun Yat-sen UniversityGuangzhou 510055China Beijing Laboratory of oral Health Capital Medical UniversityBeijing 100050China Department of oral pathology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100050China Research Unit of Precision Pathologic Diagnosis in Tumors of the oral and Maxillofacial Regions Chinese Academy of Medical SciencesBeijing 100050China BGI-Qingdao BGI-ShenzhenQingdao 266555China

The gingiva is a key oral barrier that protects oral tissues from various stimuli.A loss of gingival tissue homeostasis causes periodontitis,one of the most prevalent inflammatory diseases in *** human gingiva exists as a complex cell network comprising specialized *** understand the tissue-specific pathophysiology of the gingiva,we applied a recently developed spatial enhanced resolution omics-sequencing(Stereo-seq)technique to obtain a spatial transcriptome(ST)atlas of the gingiva in healthy individuals and periodontitis *** utilizing Stereo-seq,we identified the major cell types present in the gingiva,which included epithelial cells,fibroblasts,endothelial cells,and immune cells,as well as subgroups of epithelial cells and immune *** further observed that inflammation-related signalling pathways,such as the JAK-STAT and NF-κB signalling pathways,were significantly upregulated in the endothelial cells of the gingiva of periodontitis patients compared with those of healthy ***,we characterized the spatial distribution of periodontitis risk genes in the gingiva and found that the expression of IFI16 was significantly increased in endothelial cells of inflamed *** conclusion,our Stereo-seq findings may facilitate the development of innovative therapeutic strategies for periodontitis by mapping periodontitis-relevant genes and pathways and effector cells.

关键词： spatial transcriptomics gingiva periodontal disease periodontitis risk genes

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Advances in oral mesenchymal stem cell-derived extracellular vesicles in health and disease

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Genes & Diseases 2024年第1期11卷 346-357页

作者： Huanyu Luo Anahid Ahmadi Birjandi Feilong Ren Tianmeng Sun Paul T.Sharpe Hongchen Sun Zhengwen An Department of oral Biology Jilin Provincial Key Laboratory of Tooth Development and Bone RemodelingSchool and Hospital of StomatologyJilin UniversityChangchunJilin 130021China Faculty of Dentistry Oral&Craniofacial SciencesCentre for Craniofacial and Regenerative BiologyKing's College LondonLondonSE19RTUK Department of oral pathology Jilin Provincial Key Laboratory of Tooth Development and Bone RemodelingSchool and Hospital of StomatologyJilin UniversityChangchunJilin 130021China

Extracellular vesicles(EVs)are nano-size vesicles secreted naturally by all cells into the extracellular space and have been recognized as important cell-cell mediators in multicel-lular *** contain nucleic acids,proteins,lipids,and other cellular components,regulating many basic biological processes and playing an important role in regenerative med-icine and *** can be traced to their cells of origin and exhibit a similar ***,EVs demonstrate low immunogenicity,good biocompatibility,and fewer side ef-fects,compared to their parent *** stem cells(MsCs)are one of the most important resource cells for EVs,with a great capacity for self-renewal and multipotent differ-entiation,and play an essential role in stem cell *** mechanism of MsC therapy was thought to be attributed to the differentiation of MsCs after targeted migration,as previously ***,emerging evidence shows the previously unknown role of MsC-derived para-crine factors in stem cell *** EVs derived from oral tissue MSCs(OMSC-EVs),show more advantages than those of all other MsCs in tissue repair and regeneration,due to their lower invasiveness and easier accessibility for sample ***,we systematically review the biogenesis and biological characteristics of OMSC-EVs,as well as the role of OMsC-EVs in intercellular ***,we discuss the potential therapeutic roles of OMSC-EVs in oral and systemic *** highlight the current challenges and future directions of OMSC-EVs to focus more attention on clinical *** aim to provide valuable insights for the explorative clinical application of OMSC-EVs.

关键词： Disease Extracellular vesicles oral tissue MSC Therapeutic application Tissue regeneration

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Microsurgical management of radicular cyst using guided tissue regeneration technique:A case report

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World Journal of Clinical Cases 2024年第7期12卷 1346-1355页

作者： Juan Carlos Gómez Mireles Eugenia Karina Martínez Carrillo Katia Alcalá Barbosa Evangelina Gutiérrez Cortés Javier González Ramos Luis Antonio González Gómez Rubén Alberto Bayardo González Sarah Monserrat Lomelí Martínez Periodontics specialty Department of Integral Dentistry ClinicsCentro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajara 44340Mexico Endodontics specialty Department of Integral Dentistry ClinicsCentro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajara 44340Mexico Endodontics specialty Department of ClinicsCentro Universitario de Los AltosUniversidad de GuadalajaraTepatitlán de Morelos 47620Mexico specialty in oral pathology Surgical-Stomatological DepartmentAutonomous University of GuadalajaraZapopan 45129Mexico Independent Researcher Guadalajara 44340Mexico Department of Integral Dentistry Clinics Centro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajara 44340Mexico Department of Medical and Life Sciences Centro Universitario de la CiénegaUniversidad de GuadalajaraOcotlán 47810Mexico Master of Public Health Department of Well-being and Sustainable DevelopmentCentro Universitario del NorteUniversidad de GuadalajaraColotlán 46200Mexico

BACKGROUND Radicular cyst is a lesion of odontogenic origin that arises from epithelial remains due to periapical periodontitis caused by inflammatory reactions generated at the apex of affected teeth with infected or necrotic *** therapeutic mana gement of radicular cysts is *** is only one case report of enucleation of a radicular cyst managed with microsurgery and apicoectomy,but without the use of the guided tissue regeneration(GTR)technique in the same surgical *** present clinical case describes the management of a radicular cyst with microsurgical approach,performance of an apicoectomy of the tooth associated with the entity,application of GTR technique,use of a resorbable membrane of type I bovine collagen,and bovine *** SUMMARY A 68-year-old patient presented with a radicular cyst from an upper lateral *** microsurgical management used was aimed at enucleating the chemical membrane,performing apicoectomy of the tooth along with careful and precise retrograde filling,and implementing GTR technique using a resorbable collagen membrane and bovine *** diagnosis of radicular cyst was confirmed using histopathological *** patient underwent follow-up evaluations at 10 and 30 d *** 4 months postoperative evaluation,she remained asymptomatic,and radiographs showed significant periapical healing with adequate bone *** These results suggest that microsurgical management using the GTR technique with collagen membrane and xenograft,contributes to bone regeneration.

关键词： Odontogenic cysts Apical periodontal cyst Dental root end cyst Case report

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Classificatory updates in verrucous and cuniculatum carcinomas:Insights from the 5^(th) edition of WHO-IARC head and neck tumor classification

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World Journal of Clinical Oncology 2024年第4期15卷 464-467页

作者： Felipe Martins Silveira Lauren Frenzel Schuch Ronell Bologna-Molina Department of Diagnostics in oral pathology and oral Medicine Faculty of DentistryUniversidad de la RepúblicaMontevideo 1600Uruguay Department of oral pathology Universidad Juarez del Estado de DurangoDurango 13400Mexico

The International Agency for Research on Cancer(IARC)and World Health Organization(WHO)collaboratively produce the'WHO Blue Books'essential tools standardizing the diagnostic process for human *** updates in this classification accommodate emerging molecular discoveries,advances in immunohistochemical techniques,and evolving clinical *** 5th edition of the WHO/IARC classification of head and neck tumors refines the'oral Cavity and Mobile Tongue'chapter,including sections for non-neoplastic lesions,epithelial tumors,and tumors of uncertain ***,the epithelial tumors section is rearranged by tumor behavior,starting with benign squamous papillomas and progressing through potentially malignant oral disorders to oral squamous cell carcinoma(OSCC).The section on OSCC reflects recent information on epidemiology,pathogenesis,and histological prognostic *** is the specific categorization of verrucous carcinoma(VC)and carcinoma cuniculatum(CC),both associated with the oral cavity and distinct in clinical and histologic *** classification adjustment emphasizes the oral cavity as their predominant site in the head and *** specific sections for VC and CC aims to provide comprehensive insights into these unique subtypes,elucidating their clinical features,distinct histological characteristics,prevalence,significance,and clinical *** categorizing these subtypes into specific sections,the 5th edition of the WHO classification aims to provide a more nuanced and detailed account,enhancing our understanding of these specific variants within the broader spectrum of head and neck tumors.

关键词： World Health Organization Squamous cell carcinoma of head and neck Verrucous carcinoma Mouth neoplasms

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Comparison of the Anatomy and Adaptability of Reconstructed Teeth with Natural Teeth:An Innovative Approach in Forensic Dentistry

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Journal of Forensic Science and Medicine 2024年第1期10卷 47-54页

作者： Supraja S P M Tejaswi Ravikanth Manyam Mohan Kumar Pasupuleti Swetha P Ramesh Kumar Budumuru Department of oral and Maxillofacial pathology Vishnu Dental CollegeBhimavaramAndhra PradeshIndia Vishnu Dental College BhimavaramAndhra PradeshIndia Department of Periodontics and Implantology Vishnu Dental CollegeBhimavaramAndhra PradeshIndia Department of oral Medicine and Radiology Vishnu Dental CollegeBhimavaramAndhra PradeshIndia

Background:Forensic tooth reconstruction is the technique of reconstructing the morphology of a missing tooth from the intra-alveolar morphology of dental sockets from skeletal *** and Objectives:The aim and objective of the study are to compare and investigate whether the anatomy and adaptability of reconstructed teeth simulate with the natural tooth and to investigate whether the dental materials have potential in reconstruction of *** and Methods:An in vitro experimental study was undertaken on a human *** to the Fédération Dentaire Internationale,charting will be done based on the number of teeth *** entire study will be conducted in three phases using dental *** 1 comprised preparation for negative replica,where an impression will be taken,Phase 2 comprised preparation of a positive replica or cast,and Phase 3 comprised tooth reconstruction using the flowable ***:The specimen tooth(which had been taken from its socket)and the newly constructed tooth were compared,and when the length of the newly constructed root was measured using digital vernier calipers,there was a disparity of 0.5-1 *** cone-beam computed tomography radiographs demonstrated the necessary ***:The present study demonstrated that dental information can be obtained even when teeth are absent postmortem by making an attempt to recreate the teeth using dental materials while documenting the intra-alveolar anatomy of the dental root socket.

关键词： Adaptability anatomy reconstruction teeth

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CD97 inhibits osteoclast differentiation via Rap1a/ERK pathway under compression

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International Journal of oral Science 2024年第1期16卷 134-144页

作者： Xuan Zhou Xinjia Cai Fengyang Jing Xuefen Li Jianyun Zhang Heyu Zhang Tiejun Li Department of oral pathology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental MaterialsBeijingChina Research Unit of Precision Pathologic Diagnosis in Tumors of the oral and Maxillofacial Regions Chinese Academy of Medical Sciences(2019RU034)BeijingChina Central Laboratory Peking University School and Hospital of StomatologyBeijingChina

Acceleration of tooth movement during orthodontic treatment is challenging, with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step. Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages, especially adhesion G protein-coupled receptors (aGPCRs), play important roles in force ***, its role in the regulation of osteoclast differentiation remains unclear. Herein, through single-cell analysis, we revealed that CD97, a novel mechanosensitive aGPCR, was expressed in macrophages. Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation. It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation. RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression. Consistently, we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity, thereby accelerating tooth movement. In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

关键词： CD97 osteoclast inhibited

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Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma

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International Journal of oral Science 2024年第1期16卷 110-121页

作者： Zheqi Liu Zhen Zhang Yu Zhang Wenkai Zhou Xu Zhang Canbang Peng Tong Ji Xin Zou Zhiyuan Zhang Zhenhu Ren Department of oral and Maxillofacial-Head and Neck Oncology Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of Stomatology&Shanghai Research Institute of StomatologyShanghaiChina Department of oral and Maxillofacial Surgery Zhongshan HospitalFudan UniversityShanghaiChina School and Hospital of Stomatology Kunming Medical UniversityKunmingChina Center for Tumor Diagnosis&Therapy Jinshan HospitalFudan UniversityShanghaiChina Department of pathology Jinshan HospitalFudan UniversityShanghaiChina Hainan Western Central Hospital Academician Zhang Zhiyuan Team Innovation CenterDanzhouChina

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-βexpression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.

关键词： CXCL12 microenvironment squamous

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