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A DNA tetrahedron-based ferroptosis-suppressing nanoparticle: superior delivery of curcumin and alleviation of diabetic osteoporosis

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Bone Research 2024年第1期12卷 227-239页

作者： Yong Li Zhengwen Cai Wenjuan Ma Long Bai En Luo Yunfeng Lin State Key Laboratory of oral Diseases&National Center for Stomatology&National Clinical Research Center for oral Diseases West China Hospital of StomatologySichuan UniversityChengduSichuan 610041PR China Department of oral and maxillofacial surgery Affiliated Stomatological HospitalSouthwest Medical UniversityLuzhouSichuan 646000PR China Sichuan Provincial Engineering Research Center of oral Biomaterials ChengduSichuan 610041China

Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment strategies.In patients with diabetes,the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells(BMSCs),leading to significant skeletal changes.To address this issue,we aimed to target ferroptosis and propose a novel therapeutic approach for the treatment of DOP.We synthesized ferroptosis-suppressing nanoparticles,which could deliver curcumin,a natural compound,to the bone marrow using tetrahedral framework nucleic acid(tFNA).This delivery system demonstrated excellent curcumin bioavailability and stability,as well as synergistic properties with tFNA.Both in vitro and in vivo experiments revealed that nanoparticles could enhance mitochondrial function by activating the nuclear factor E2-related factor 2(NRF2)/glutathione peroxidase 4(GPX4)pathway,inhibiting ferroptosis,promoting the osteogenic differentiation of BMSCs in the diabetic microenvironment,reducing trabecular loss,and increasing bone formation.These findings suggest that curcumin-containing DNA tetrahedron-based ferroptosissuppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.

关键词： curcumin osteoporosis diabetic

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Sema3A secreted by sensory nerve induces bone formation under mechanical loads

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International Journal of oral Science 2024年第1期16卷 62-72页

作者： Hongxiang Mei Zhengzheng Li Qinyi Lv Xingjian Li Yumeng Wu Qingchen Feng Zhishen Jiang Yimei Zhou Yule Zheng Ziqi Gao Jiawei Zhou Chen Jiang Shishu Huang Juan Li State Key Laboratory of oral Diseases&National Center for Stomatology&National Clinical Research Center for oral Diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina Department of Orthopedic surgery and Orthopedic Research Institute West China HospitalSichuan UniversityChengduChina

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

关键词： Sema3A formation overload

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Role of oncogenic long noncoding RNA KCNQ1OT1 in colon cancer

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Oncology Research 2024年第3期32卷 585-596页

作者： GANG LIU LEI SHI BIN WANG ZEHUI WU HAIYUAN ZHAO TIANYU ZHAO LIANGHUI SHI Department of Gastrointestinal surgery First ffiliated Hospital of Wannan Medical CollegeWuhu241001China Chongqing Key Laboratory of oral Diseases and Biomedical Sciences Stomatological Hospital of Chongqing Medical UniversityChongqing401147China

The role of lncRNA KCNQ1 opposite strand/antisense transcript 1(KCNQ1OT1)in colon cancer involves various tumorigenic processes and has been studed widely.However,the mechanism by which it promotes colon cancer remains unclear.Retrovirnl vector pSEB61 was retroftted in established HCT116 siKCN and SW480-siKCN cells to silence KCNQ1 OT1.Cellular proliferation was measured using CCK8 assay,and flow cytometry(FCM)detected cell cydle changes.RNA sequencing(RNA Seq)analysis showed differentially expressed genes(DEGs).Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were carried out to analyze enriched functions and signaling pathways.RT-qPCR,immunofluorescence,and western blotting were carried out to validate downstream gene expressions.The effects of tumorigenesis were evaluated in BALB/c nude mice by tumor xenografts.Our data revealed that the silencing of KONQ1OT1 in HCT116 and SW480 cells slowed cell growth and decreased the number of cells in the G2/M phase.RNA-Seq analysis showed the data of DEGs enriched in various GO and KEGG pathways such as DNA replication and cell cyde.RT qPCR,immunofluorescence,and western blotting confirmed downstream CCNE2 and PCNA gene expressions.HCT116 siKCN cells signifcantly suppressed tumorigenesis in BALB/c nude mice.Our study suggests that lncRNA KCNQ1OT1 may provide a promising therapeutic strategy for colon cancer.

关键词： lncRNA KCNQ1OT1 Colon cancer HCT116 cells Tumorigenesis

Factors influencing Frey syndrome after parotidectomy with acellular dermal matrix

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World Journal of Clinical Cases 2024年第9期12卷 1578-1584页

作者： Xian-Da Chai Huan Jiang Ling-Ling Tang Jing Zhang Long-Fei Yue Department of oral and maxillofacial surgery People’s Hospital of AnshunAnshun 561000Guizhou ProvinceChina Department of General Practice People’s Hospital of AnshunAnshun 561000Guizhou ProvinceChina

BACKGROUND Frey syndrome,also known as ototemporal nerve syndrome or gustatory sweating syndrome,is one of the most common complications of parotid gland surgery.This condition is characterized by abnormal sensations in the facial skin accompanied by episodes of flushing and sweating triggered by cognitive processes,visual stimuli,or eating.AIM To investigate the preventive effect of acellular dermal matrix(ADM)on Frey syndrome after parotid tumor resection and analyzed the effects of Frey syndrome across various surgical methods and other factors involved in parotid tumor resection.METHODS Retrospective data from 82 patients were analyzed to assess the correlation between sex,age,resection sample size,operation time,operation mode,ADM usage,and occurrence of postoperative Frey syndrome.RESULTS Among the 82 patients,the incidence of Frey syndrome was 56.1%.There were no significant differences in sex,age,or operation time between the two groups(P>0.05).However,there was a significant difference between ADM implantation and occurrence of Frey syndrome(P<0.05).ADM application could reduce the variation in the incidence of Frey syndrome across different operation modes.CONCLUSION ADM can effectively prevent Frey syndrome and delay its onset.

关键词： Parotid gland tumor Frey syndrome Acellular dermal matrix Acellular allogenic dermal matrix

Anatomical variation in the internal jugular vein:potential risk factors for central venous catheterization-a case report

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World Journal of Emergency Medicine 2024年第4期15卷 316-318页

作者： Yidan Shan Weijia Huang Department of oral and maxillofacial surgery the Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310009China

Central venous catheterization(CVC)is an invasive medical procedure used to measure central venous pressure and provides a stable route for continuous drug administration.CVC is widely used in the emergency department and intensive care units.It is typically performed by inserting a catheter through the internal jugular vein(IJV)into the superior vena cava near the right atrium.[1,2]While catheterization is a fundamental skill proficiently performed by healthcare professionals,lethal complications may occasionally occur because of undesirable positioning,depth and diameter.

关键词： venous catheter jugular

A Comparative Study of Mandibular Fractures in Senegal: Children vs. Adults

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Open Journal of Stomatology 2024年第2期14卷 72-76页

作者： Paul Niang Department of oral surgery Cheikh Anta Diop University Dakar Senegal

Introduction: The commonest maxillofacial fractures involve the mandible. Age can be considered among influential factors. Aim of the Study: To compare mandibular fractures between children and adults from the beginning up to the treatment in Senegal. Patients and Method: A three-year retrospective study was conducted in a university hospital. The medical records of patients admitted for maxillofacial injuries were reviewed. Patient and injury-related variables including age, gender, etiology, average consultation delay, anatomic location of fracture and treatment were compared up to age of 15 and beyond that. Results: Considering 272 casualties, maxillofacial fractures were less frequent among children than adults (36.7% and 59.7%) and were mainly mandibular (90.1% and 91.4%). Male predilection (sex ratio of 2.4 and 4.9) was twice (2) as pronounced from the age of 16. The average consultation delay was two (2) times shorter for children. Road traffic accidents which predominated among children (33.9%) had comparable frequency (32.3%) although they were outnumbered by assault (37.6%) among adults. Fractures occurred mainly on the corpus (90.1% and 90.4%), particularly on parasymphysis (40.1%) up to the age of 15, whereas angle fractures increased (8.5% to 19.6%) and joint damage decreased afterwards. Intra-oral orthopedic procedures (91.2% and 92.6%) in which mandibular retention splints were more common (37.3%) up to the age of 15 then arch ligatures (49%) were then widely favored. Conclusion: Differences relating to the distribution of causes but also to the anatomic location on the corpus and to the choice of intra-oral orthopedic procedures within overall similarities between children and adults regarding the male predilection, the frequency of road traffic accidents, the mandibular injuries, but also the school therapeutic attitude consisting of favoring the orthopedic option.

关键词： Fracture Mandible Child Adult

Bioinspired mineral-in-shell nanoarchitectonics:Functional empowerment of mineral precursors for guiding intradentinal mineralization

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Nano Research 2024年第5期17卷 4338-4349页

作者： Xiaoran Zheng Yang Liu Mingjing Li Yuyan Li Wanshan Gao Rongmin Qiu Jiaqi Xing Jiaojiao Yang Yantao Chen Xinyuan Xu Mingming Ding Jun Luo Jianshu Li College of Polymer Science and Engineering State Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu 610065China College of Stomatology Hospital of Stomatology Guangxi Medical UniversityGuangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and ReconstructionGuangxi Clinical Research Center for Craniofacial DeformityGuangxi Key Laboratory of Oral and Maxillofacial Surgery Disease TreatmentGuangxi Health Commission Key Laboratory of Prevention and Treatment for Oral Infectious DiseasesNanning 530021China State Key Laboratory of oral Diseases West China Hospital of StomatologySichuan UniversityChengdu 610041China Shenzhen Key Laboratory of Environmental Chemistry and Ecological Remediation College of Chemistry and Environmental EngineeringShenzhen UniversityShenzhen 518060China Med-X Center for Material Sichuan UniversityChengdu 610041China

Effective mineralization of biological structures poses a significant challenge in hard tissue engineering as it necessitates overcoming geometric complexities and multistep biomineralization processes.In this regard,we propose“mineral-in-shell nanoarchitectonics”,inspired by the nanostructure of matrix vesicles,which can influence multiple mineralization pathways.Our nanostructural design empowers mineral precursors with tailorable properties through encapsulating amorphous calcium phosphate within a multifunctional tannic acid(TA)and silk fibroin(SF)nanoshell.The bioinspired nanosystem facilitates efficient recruitment of mineral precursors throughout the dentin structures,followed by large-scale intradentinal mineralization both in vitro and in vivo,which provides persistent protection against external stimuli.Theoretical simulations combined with experimental studies attribute the success of intradentinal mineralization to the TA-SF nanoshell,which exhibits a strong affinity for the dentin structure,stabilizing amorphous precursors and thereby facilitating concomitant mineral formation.Overall,this bioinspired mineral-in-shell nanoarchitectonics shows a promising prospect for hard tissue repair and serves as a blueprint for next-generation biomineralization-associated materials.

关键词： mineral-in-shell nanohybrids self-assembly biomineralization dentinal tubule occlusion dental hypersensitivity

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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Short- and long-term outcomes of surgical treatment in patients with intestinal Behcet’s disease

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World Journal of Gastrointestinal surgery 2024年第2期16卷 429-437页

作者： Min Young Park Yong Sik Yoon Jae Ha Park Jong Lyul Lee Chang Sik Yu Division of Colon and Rectal surgery Department of SurgeryYonsei University College of MedicineSeoul 03722South Korea Division of Colon and Rectal surgery Department of SurgeryUniversity of Ulsan College of MedicineAsan Medical CenterSeoul 05505South Korea

BACKGROUND Behcet’s disease(BD),a chronic vasculitic disorder affecting multiple organs,is characterized by recurrent oral and genital ulcers,arthritis,vasculitis,and intes-tinal ulcers.Although intestinal involvement of BD is common in East Asia,the efficacy and long-term outcomes of surgical treatment of intestinal BD still remain to be established.AIM To evaluate the postoperative clinical course of intestinal BD and determine factors associated with its recurrence.METHODS Data from patients who underwent surgical treatment for intestinal BD between January 2010 and August 2021 were retrospectively reviewed.Patients’demo-graphics,clinical features,postoperative course,complications,and follow-up data were evaluated.RESULTS We analyzed 39 surgeries in 31 patients.The mean patient age was 45.1 years,and the mean interval between the diagnosis of intestinal BD and surgical treatment was 4.9 years(range 1.0-8.0 years).The most common indication for surgery was medical intractability(n=16,41.0%),followed by fistula or abscess(n=11,28.2%).Laparoscopic approaches were used in 19 patients(48.7%),and 5 patients(12.8%)underwent emergency surgeries.The most common surgical procedure was ileocecal resection(n=18,46.2%),followed by right colectomy(n=11,28.2%).A diverting stoma was created in only one patient(2.6%).During a mean follow-up period of 45(range 8-72)months,eight cases(20.5%)of recurrence in five patients required reoperation.The interval between operations was 12.1 months(range 6.3-17.8 mo).Four patients(10.3%)experienced recurrence within 1 year postoperatively,and all eight recurrences occurred within 2 years of the initial surgery.The reoperation rates at 1 and 3 years were 10.3%and 20.5%,respectively.A redo ileocolic anastomosis was performed in all recurrent cases.In multivariate Cox regression analysis,emergency surgery[hazard ratio(HR)9.357,95%confidence interval(CI):1.608-54.453,P=0.013]and elevated C-reactive protein(CRP)levels(HR 1.154,95%CI:1.002–1.328,P=0.047),but not medication use,were predictors

关键词： Behcet syndrome Intestinal General surgery Recurrence Risk factors