Oral squamous cell carcinoma(OSCC)is the most common oral cancers worldwide,accounting for over 90%of all oral malignancies[1].Despite encouraging improvements in therapeutic approaches,including surgical resection,ch...Oral squamous cell carcinoma(OSCC)is the most common oral cancers worldwide,accounting for over 90%of all oral malignancies[1].Despite encouraging improvements in therapeutic approaches,including surgical resection,chemotherapy,and radiotherapy,the five-year overall survival rate of OSCC has not been improved significantly over the past decades,mainly due to the high ratio of tumor recurrence and metastasis.展开更多
Recently,magnesium(Mg)alloys have attracted extensive attention as biodegradable implant materials.However,cyclic loading and the corrosive environment of the body are significant challenges for the practical use of a...Recently,magnesium(Mg)alloys have attracted extensive attention as biodegradable implant materials.However,cyclic loading and the corrosive environment of the body are significant challenges for the practical use of alloys,and there are few studies on this topic.In this study,we conducted a four-point bending fatigue test for 86,400 cycles(12 h)in simulated body fluid(SBF),plasma,and whole blood with an AZ series alloy Mg-9Al-0.5Zn-0.27Mn-0.12Ag,to examine the effects of inorganic ions,organic particles,blood cells,and cyclic loading on Mg alloy corrosion.The Mg^(2+)concentration and solution pH were measured before and after experimentation,and the sample surfaces were characterized by 3D digital microscopy,scanning electron microscopy(SEM),energy-dispersive X-ray spectroscopy(EDS),Fourier-transform infrared(FTIR)spectroscopy,Raman spectroscopy,and X-ray photoelectron spectroscopy(XPS).Our results showed that in the non-loading condition,a porous and weak inorganic product layer(mainly Mg/Ca phosphate and carbonate)formed on the surface of the Mg alloy sample immersed in SBF,which hardly had a protective effect on Mg alloy corrosion.For the samples immersed in plasma,the organic particles promoted the formation of an organic and more compact product layer,which protected the Mg alloy from severe corrosion.For the sample immersed in whole blood,the blood cells affected organic particle deposition on the product layer and thus interfered with the formation of an organic compact product layer,which slightly accelerated the corrosion process.Furthermore,cyclic loading damaged the layer integrity and significantly increased the corrosion rates of all the studied materials compared to the samples not subjected to cyclic loading.Nonetheless,under cyclic loading,blood cells adsorbed on the Mg alloy surfaces,and formed films,which protected the Mg alloy substrate and delayed Mg alloy corrosion.展开更多
The correlation between microbiota plays a vital role in the progression of periodontal disease.This study investigated the in situ interaction networks between periodontal pathogens in periodontal and peri-implant di...The correlation between microbiota plays a vital role in the progression of periodontal disease.This study investigated the in situ interaction networks between periodontal pathogens in periodontal and peri-implant disease.We used quantitative real-time polymerase chain reaction and Pearson’s correlation coefficients to quantify the copy numbers and correlations of four oral core species—Fusobacterium nucleatum,Porphyromonas gingivalis,Prevotella intermedia,and Streptococcus gordonii—from 80 subgingival sites(healthy and with periodontitis or gingivitis)in patients with periodontitis,and 68 subgingival sites(healthy and with periodontitis,gingivitis,peri-implantitis,or peri-implant mucositis)in patients with implants.The highest bacterial counts were observed for Porphyromonas gingivalis and Prevotella intermedia at all the sites.Within the same cohorts,the bacterial loads were greater at diseased sites than at healthy sites.Bacterial counts did not differ among clinical sites in the same group(P>0.05)but differed between periodontitis and peri-implant mucositis sites in the two groups.Porphyromonas gingivalis,F.nucleatum,and Prevotella intermedia had strong correlations at gingivitis and healthy sites and moderate correlations at periodontitis sites in patients with periodontitis.In patients with implants,Prevotella intermedia,F.nucleatum,and S.gordonii had strong correlations only at peri-implantitis sites.Also,based on metagenomic analysis,F.nucleatum and Prevotella intermedia were significantly correlated at the subgingival plaque in peri-implantitis and periodontitis samples.Our results suggest that variations in microbe-microbe interactions in subgingival plaque reflect changes in the progression of periodontal disease,providing a new perspective for understanding the mechanisms of periodontitis and peri-implantitis.展开更多
Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of uniq...Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of unique clinical features, OMS is difficult to distinguish from other types of rhinosinusitis. Besides, the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis. Its current diagnosis and treatment are thus facing great difficulties. The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS. However, this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality. Based on systematically reviewed literature and practical experiences of expert members, our consensus focuses on characteristics, symptoms, classification and diagnosis of OMS, and further put forward multidisciplinary treatment decisions for OMS, as well as the common treatment complications and relative managements. This consensus aims to increase attention to OMS, and optimize the clinical diagnosis and decision-making of OMS, which finally provides evidence-based options for OMS clinical management.展开更多
In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we dev...In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these limitations.We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling method.We explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL composites.The 5 and 10 wt%Mg-1Ca/PCL composites were found to have good biocompatibility.Moreover,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure PCL.In vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth.Microcomputed tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects.Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect.Therefore,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application.Statement of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects.However,there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds.This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities.Furthermore,the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold.The obtained porous scaffolds can significantly promote the regeneration of bone defects.展开更多
Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy pre...Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes.This study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone loss.Methods:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis.Micro-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also investigated.The underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),etc.Results:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs.Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting osteogenesis.Conclusion:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.展开更多
Osteoporosis is a frequently occurring bone remodeling disorder worldwide with one characteristic being decreasing bone mineral density and a predisposition to bone fracture,which diminishes patients’quality of life....Osteoporosis is a frequently occurring bone remodeling disorder worldwide with one characteristic being decreasing bone mineral density and a predisposition to bone fracture,which diminishes patients’quality of life.Several studies showed that imbalance between the osteogenesis and adipogenesis of bone marrow mesenchymal stem cells(BMSCs)took part in the development of osteoporosis.In previous study,we found MIR22HG regulated the osteogenesis of human BMSCs positively.In this study,we found that MIR22HG was decreased during the adipogenesis of human BMSCs and exerted negative effects on adipogenesis with the involvement of Wnt/β-catenin signaling pathway both in vitro and in vivo.Nitazoxanide could inhibit Wnt signaling and relieve MIR22HG’s suppression on adipogenesis.These findings indicated that MIR22HG had great potential in clinical application for osteoporosis treatment and prevention.展开更多
BACKGROUND Loss of motor function in the trapezius muscle is one complication of radical neck dissection after cutting the accessory nerve(AN) during surgery.Nerve repair is an effective method to restore trapezius mu...BACKGROUND Loss of motor function in the trapezius muscle is one complication of radical neck dissection after cutting the accessory nerve(AN) during surgery.Nerve repair is an effective method to restore trapezius muscle function,and includes neurolysis,direct suture,and nerve grafting.The suprascapular nerve(SCN) and AN are next to each other in position.The function of the AN and SCN in shoulder elevation and abduction movement is synergistic.SCN might be considered by surgeons for AN reanimation.AIM To obtain anatomical and clinical data for partial suprascapular nerve-to-AN transfer.METHODS Ten sides of cadavers perfused with formalin were obtained from the Department of Human Anatomy,Histology and Embryology,Peking University Health Science Center.The SCN(n = 10) and AN(n = 10) were carefully dissected in the posterior triangle of the neck,and the trapezius muscle was dissected to fully display the accessory nerve.The length of the SCN from the origin of the brachial plexus(a point) to the scapular notch(b point) and the distance of the SCN from the origin point(a point) to the point(c point) where the AN entered the border of the trapezius muscle were measured.The length and branches of the AN in the trapezius muscle were measured.A female patient aged 55 years underwent surgery for partial SCN to AN transfer at Department of Oral and Maxillofacial Surgery,Peking University School and Hospital of Stomatology.The patient suffered from recurrent upper gingival cancer.Radical neck dissection was performed on the right side,and the right AN was removed at the intersection between the nerve and the posterior border of the SCM muscle.One-third of the diameter of the SCN was cut off,and combined epineurial and perineurial sutures were applied between the distal end of the cut-off fascicles of the SCN and the proximal end of the AN without tension.Both subjective and objective evaluations were performed before,three months after,and nine months after surgery.For the subjective evaluation,the questionnaire included the Neck Dissection Impairment Index(NDII) and the Constant Shoulder Scale.Electromyography was used for the objective examination.Data were analyzed using t tests with SPSS 19.0 software to determine the relationship between the length of the SCN and the linear distance.A P value of < 0.05 was considered as statistically significant.RESULTS The whole length of the AN in the trapezius muscle was 16.89 cm.The average numbers of branches distributed in the descending,horizontal and ascending portions were 3.8,2.6 and 2.2,respectively.The diameter of the AN was 1.94 mm at the anterior border of the trapezius.The length of the suprascapular nerve from the origin of the brachial plexus to the scapular notch was longer than the distance of the suprascapular nerve from the origin point to the point where the accessory nerve entered the upper edge of the trapezius muscle.The amplitude of trapezius muscle electromyography indicated that both the horizontal and ascending portions of the trapezius muscle on the right side had better function than the left side nine months after surgery.The results showed that the right-sided supraspinatus and infraspinatus muscles did not lose more function than the left side.CONCLUSION Based on anatomical data and clinical application,partial suprascapular nerve-to-AN transfer could be achieved and may improve innervation of the affected trapezius muscle after radical neck dissection.展开更多
Dear Editor,Orofacial cleft(OFC),which includes cleft lip and/or palate(CL/P)and cleft palate(CP),is the most common congenital craniofacial structural disorder,with a prevalence of 1.416%。among live infants worldwid...Dear Editor,Orofacial cleft(OFC),which includes cleft lip and/or palate(CL/P)and cleft palate(CP),is the most common congenital craniofacial structural disorder,with a prevalence of 1.416%。among live infants worldwide(Massenburg et al.,2021).Nonsyndromic OFC(NSOFC),which does not contain other malformations as syndromic OFC(SOFC),accounts for 70%of cases and is believed to have complex etiologies.Notably,it has been established that genetic factors play a crucial role in the occurrence of NSOFC(Dixon et al.,2011).展开更多
Additive manufacturing has received attention for the fabrication of medical implants that have customized and complicated structures.Biodegradable Zn metals are revolutionary materials for orthopedic implants.In this...Additive manufacturing has received attention for the fabrication of medical implants that have customized and complicated structures.Biodegradable Zn metals are revolutionary materials for orthopedic implants.In this study,pure Zn porous scaffolds with diamond structures were fabricated using customized laser powder bed fusion(L-PBF)technology.First,the mechanical properties,corrosion behavior,and biocompatibility of the pure Zn porous scaffolds were characterized in vitro.The scaffolds were then implanted into the rabbit femur critical-size bone defect model for 24 weeks.The results showed that the pure Zn porous scaffolds had compressive strength and rigidity comparable to those of cancellous bone,as well as relatively suitable degradation rates for bone regeneration.A benign host response was observed using hematoxylin and eosin(HE)staining of the heart,liver,spleen,lungs,and kidneys.Moreover,the pure Zn porous scaffold showed good biocompatibility and osteogenic promotion ability in vivo.This study showed that pure Zn porous scaffolds with customized structures fabricated using L-PBF represent a promising biodegradable solution for treating large bone defects.展开更多
Oral leukoplakia is a common precursor lesion of oral squamous cell carcinoma,which indicates a high potential of malignancy.The malignant transformation of oral leukoplakia seriously affects patient survival and qual...Oral leukoplakia is a common precursor lesion of oral squamous cell carcinoma,which indicates a high potential of malignancy.The malignant transformation of oral leukoplakia seriously affects patient survival and quality of life;however,it is difficult to identify oral leukoplakia patients who will develop carcinoma because no biomarker exists to predict malignant transformation for effective clinical management.As a major problem in the field of head and neck pathologies,it is imperative to identify biomarkers of malignant transformation in oral leukoplakia.In this review,we discuss the potential biomarkers of malignant transformation reported in the literature and explore the translational probabilities from bench to bedside.Although no single biomarker has yet been applied in the clinical setting,profiling for genomic instability might be a promising adjunct.展开更多
Hydrogels are extracellular-matrix-like biomimetic materials that have wide biomedical applications in tissue engineering and drug delivery.However,most hydrogels cannot simultaneously fulfill the mechanical and cell ...Hydrogels are extracellular-matrix-like biomimetic materials that have wide biomedical applications in tissue engineering and drug delivery.However,most hydrogels cannot simultaneously fulfill the mechanical and cell compatibility requirements.In the present study,we prepared a semi-interpenetrating network composite gel(CG)by incorporating short chain chitosan(CS)into a covalent tetra-armed poly(ethylene glycol)network.In addition to satisfying physicochemical,mechanics,biocompatibility,and cell affinity requirements,this CG easily encapsulated acetylsalicylic acid(ASA)via electrostatic interactions and chain entanglement,achieving sustained release for over 14 days and thus promoting periodontal ligament stem cell(PDLSC)proliferation and osteogenic differentiation.In vivo studies corroborated the capacity of PDLSCs and ASA-laden CG to enhance new bone regeneration in situ using a mouse calvarial bone defect model.This might be attributed to PDLSCs and host mesenchymal stem cells expressing monocyte chemoattractant protein-1,which upregulated M2 macrophage recruitment and polarization in situ,indicating its appealing potential in bone tissue engineering.展开更多
To flourish,cancers greatly depend on their surrounding tumor microenvironment(TME),and cancer-associated fibroblasts(CAFs)in TME are critical for cancer occurrence and progression because of their versatile roles in ...To flourish,cancers greatly depend on their surrounding tumor microenvironment(TME),and cancer-associated fibroblasts(CAFs)in TME are critical for cancer occurrence and progression because of their versatile roles in extracellular matrix remodeling,maintenance of sternness,blood vessel formation,modulation of tumor metabolism,immune response,and promotion of cancer cell proliferation,migration,invasion,and therapeutic resistance.CAFs are highly heterogeneous stromal cells and their crosstalk with cancer cells is mediated by a complex and intricate signaling network consisting of transforming growth factor-beta,phosphoinositide 3-kinase/AKT/mammalian target of rapamycin,mitogen-activated protein kinase,Wnt,Janus kinase/signal transducers and activators of transcription,epidermal growth factor receptor,Hippo,and nuclear factor kappa-light-chain-enhancer of activated B cells,etc.,signaling pathways.These signals in CAFs exhibit their own special characteristics during the cancer progression and have the potential to be targeted for anticancer therapy.Therefore,a comprehensive understanding of these signaling cascades in interactions between cancer cells and CAFs is necessary to fully realize the pivotal roles of CAFs in cancers.Herein,in this review,we will summarize the enormous amounts of findings on the signals mediating crosstalk of CAFs with cancer cells and its related targets or trials.Further,we hypothesize three potential targeting strategies,including,namely,epithelial-mesenchymal common targets,sequential target perturbation,and crosstalk-directed signaling targets,paving the way for CAF-directed or host cell-directed antitumor therapy.展开更多
Exosomes derived from mesenchymal stem cells(MSCs)have demonstrated regenerative potential for cell-free bone tissue engineering,nevertheless,certain challenges,including the confined therapeutic potency of exosomes a...Exosomes derived from mesenchymal stem cells(MSCs)have demonstrated regenerative potential for cell-free bone tissue engineering,nevertheless,certain challenges,including the confined therapeutic potency of exosomes and ineffective delivery method,are still persisted.Here,we confirmed that hypoxic precondition could induce enhanced secretion of exosomes from stem cells from human exfoliated deciduous teeth(SHEDs)via comprehensive proteomics analysis,and the corresponding hypoxic exosomes(H-Exo)exhibited superior potential in promoting cellular angiogenesis and osteogenesis via the significant up-regulation in focal adhesion,VEGF signaling pathway,and thyroid hormone synthesis.Then,we developed a platform technology enabling the effective delivery of hypoxic exosomes with sustained release kinetics to irregular-shaped bone defects via injection.This platform is based on a simple adsorbing technique,where exosomes are adsorbed onto the surface of injectable porous poly(lactide-co-glycolide)(PLGA)microspheres with bioinspired polydopamine(PDA)coating(PMS-PDA microspheres).The PMS-PDA microspheres could effectively adsorb exosomes,show sustained release of H-Exo for 21 days with high bioactivity,and induce vascularized bone regeneration in 5-mm rat calvarial defect.These findings indicate that the hypoxic precondition and PMS-PDA porous microsphere-based exosome delivery are efficient in inducing tissue regeneration,hence facilitating the clinical translation of exosome-based therapy.展开更多
Guided bone regeneration membranes have been effectively applied in oral implantology to repair bone defects.However,typical resorbable membranes composed of collagen(Col)have insufficient mechanical properties and hi...Guided bone regeneration membranes have been effectively applied in oral implantology to repair bone defects.However,typical resorbable membranes composed of collagen(Col)have insufficient mechanical properties and high degradation rate,while non-resorbable membranes need secondary surgery.Herein,we designed a photocrosslinkable collagen/polycaprolactone methacryloyl/magnesium(Col/PCLMA/Mg)composite membrane that provided spatiotemporal support effect after photocrosslinking.Magnesium particles were added to the PCLMA solution and Col/PCLMA and Col/PCLMA/Mg membranes were developed;Col membranes and PCL membranes were used as controls.After photocrosslinking,an interpenetrating polymer network was observed by scanning electron microscopy(SEM)in Col/PCL and Col/PCL/Mg membranes.The elastic modulus,swelling behavior,cytotoxicity,cell attachment,and cell proliferation of the membranes were evaluated.Degradation behavior in vivo and in vitro was monitored according to mass change and by SEM.The membranes were implanted into calvarial bone defects of rats for 8 weeks.The Col/PCL and Col/PCL/Mg membranes displayed much higher elastic modulus(p<0.05),and a lower swelling rate(p<0.05),than Col membranes,and there were no differences in cell biocompatibility among groups(p>0.05).The Col/PCL and Col/PCL/Mg membranes had lower degradation rates than the Col membranes,both in vivo and in vitro(p<0.05).The Col/PCL/Mg groups showed enhanced osteogenic capability compared with the Col groups at week 8(p<0.05).The Col/PCL/Mg composite membrane represents a new strategy to display space maintenance and enhance osteogenic potential,which meets clinical needs.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.:82002877)the Scientific Research Foundation for Recruited Talents,West China Hospital of Stomatology,Sichuan University,China(Grant No.:QDJF2019-3)+1 种基金the Fundamental Research Funds for the Central Universities,China(Grant No.:YJ201987)Sichuan Science and Technology Program,China(Grant No.:2021ZYD0090).
文摘Oral squamous cell carcinoma(OSCC)is the most common oral cancers worldwide,accounting for over 90%of all oral malignancies[1].Despite encouraging improvements in therapeutic approaches,including surgical resection,chemotherapy,and radiotherapy,the five-year overall survival rate of OSCC has not been improved significantly over the past decades,mainly due to the high ratio of tumor recurrence and metastasis.
基金supported by the National Natural Science Foundation of China(Grant No.81771119)the National Key Research and Development Project(Governmental International S&T Innovation Cooperation Projects,Grant No.2019YFE0101100).
文摘Recently,magnesium(Mg)alloys have attracted extensive attention as biodegradable implant materials.However,cyclic loading and the corrosive environment of the body are significant challenges for the practical use of alloys,and there are few studies on this topic.In this study,we conducted a four-point bending fatigue test for 86,400 cycles(12 h)in simulated body fluid(SBF),plasma,and whole blood with an AZ series alloy Mg-9Al-0.5Zn-0.27Mn-0.12Ag,to examine the effects of inorganic ions,organic particles,blood cells,and cyclic loading on Mg alloy corrosion.The Mg^(2+)concentration and solution pH were measured before and after experimentation,and the sample surfaces were characterized by 3D digital microscopy,scanning electron microscopy(SEM),energy-dispersive X-ray spectroscopy(EDS),Fourier-transform infrared(FTIR)spectroscopy,Raman spectroscopy,and X-ray photoelectron spectroscopy(XPS).Our results showed that in the non-loading condition,a porous and weak inorganic product layer(mainly Mg/Ca phosphate and carbonate)formed on the surface of the Mg alloy sample immersed in SBF,which hardly had a protective effect on Mg alloy corrosion.For the samples immersed in plasma,the organic particles promoted the formation of an organic and more compact product layer,which protected the Mg alloy from severe corrosion.For the sample immersed in whole blood,the blood cells affected organic particle deposition on the product layer and thus interfered with the formation of an organic compact product layer,which slightly accelerated the corrosion process.Furthermore,cyclic loading damaged the layer integrity and significantly increased the corrosion rates of all the studied materials compared to the samples not subjected to cyclic loading.Nonetheless,under cyclic loading,blood cells adsorbed on the Mg alloy surfaces,and formed films,which protected the Mg alloy substrate and delayed Mg alloy corrosion.
基金supported by grants from the Peking University School of Stomatology(PKUSS20170112).
文摘The correlation between microbiota plays a vital role in the progression of periodontal disease.This study investigated the in situ interaction networks between periodontal pathogens in periodontal and peri-implant disease.We used quantitative real-time polymerase chain reaction and Pearson’s correlation coefficients to quantify the copy numbers and correlations of four oral core species—Fusobacterium nucleatum,Porphyromonas gingivalis,Prevotella intermedia,and Streptococcus gordonii—from 80 subgingival sites(healthy and with periodontitis or gingivitis)in patients with periodontitis,and 68 subgingival sites(healthy and with periodontitis,gingivitis,peri-implantitis,or peri-implant mucositis)in patients with implants.The highest bacterial counts were observed for Porphyromonas gingivalis and Prevotella intermedia at all the sites.Within the same cohorts,the bacterial loads were greater at diseased sites than at healthy sites.Bacterial counts did not differ among clinical sites in the same group(P>0.05)but differed between periodontitis and peri-implant mucositis sites in the two groups.Porphyromonas gingivalis,F.nucleatum,and Prevotella intermedia had strong correlations at gingivitis and healthy sites and moderate correlations at periodontitis sites in patients with periodontitis.In patients with implants,Prevotella intermedia,F.nucleatum,and S.gordonii had strong correlations only at peri-implantitis sites.Also,based on metagenomic analysis,F.nucleatum and Prevotella intermedia were significantly correlated at the subgingival plaque in peri-implantitis and periodontitis samples.Our results suggest that variations in microbe-microbe interactions in subgingival plaque reflect changes in the progression of periodontal disease,providing a new perspective for understanding the mechanisms of periodontitis and peri-implantitis.
基金project was supported by grants from National Natural Science Foundations of China (Nos. 82025010, 81630023, 81900917)Changjiang Scholars and Innovative Research Team (No. IRT13082)+4 种基金CAMS Innovation Fund for Medical Sciences (No. 2019-I2M-5-022)Beijing Municipal Science and Technology Commision (Nos. Z181100001618002, Z211100002921057)Capital’s Funds for Health Improvement and Research (No.CFH2022-1-1091)Beijing Municipal Administration of Hospitals’ Mission Project (No. SML20150203)Beijing Municipal Administration of Hospitals’ Dengfeng Project (No. DFL20190202)。
文摘Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of unique clinical features, OMS is difficult to distinguish from other types of rhinosinusitis. Besides, the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis. Its current diagnosis and treatment are thus facing great difficulties. The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS. However, this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality. Based on systematically reviewed literature and practical experiences of expert members, our consensus focuses on characteristics, symptoms, classification and diagnosis of OMS, and further put forward multidisciplinary treatment decisions for OMS, as well as the common treatment complications and relative managements. This consensus aims to increase attention to OMS, and optimize the clinical diagnosis and decision-making of OMS, which finally provides evidence-based options for OMS clinical management.
基金supported by the National Key R&D Program of China[grant number 2021YFC2400700]the National Natural Science Foundation of China[grant numbers 82170929,81970908 and 81771039].
文摘In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these limitations.We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling method.We explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL composites.The 5 and 10 wt%Mg-1Ca/PCL composites were found to have good biocompatibility.Moreover,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure PCL.In vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth.Microcomputed tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects.Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect.Therefore,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application.Statement of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects.However,there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds.This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities.Furthermore,the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold.The obtained porous scaffolds can significantly promote the regeneration of bone defects.
基金Beijing Natural Science Foundation,Grant/Award Number:L222145 and L222030Emerging Engineering Interdisciplinary Project and the Fundamental Research Funds for the Central Universities,Grant/Award Number:PKU2022XGK008Peking University Medicine Fund of Fostering Young Scholars’Scientific&Technological Innovation,Grant/Award Number:BMU2022PY010。
文摘Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes.This study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone loss.Methods:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis.Micro-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also investigated.The underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),etc.Results:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs.Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting osteogenesis.Conclusion:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.
基金This study was financially supported by grants from the National Natural Science Foundation of China(82071119,82071142,81700938,81772876,81800942).
文摘Osteoporosis is a frequently occurring bone remodeling disorder worldwide with one characteristic being decreasing bone mineral density and a predisposition to bone fracture,which diminishes patients’quality of life.Several studies showed that imbalance between the osteogenesis and adipogenesis of bone marrow mesenchymal stem cells(BMSCs)took part in the development of osteoporosis.In previous study,we found MIR22HG regulated the osteogenesis of human BMSCs positively.In this study,we found that MIR22HG was decreased during the adipogenesis of human BMSCs and exerted negative effects on adipogenesis with the involvement of Wnt/β-catenin signaling pathway both in vitro and in vivo.Nitazoxanide could inhibit Wnt signaling and relieve MIR22HG’s suppression on adipogenesis.These findings indicated that MIR22HG had great potential in clinical application for osteoporosis treatment and prevention.
基金Supported by Beijing Municipal Science and Technology Commission,No. Z201100005520055Education Research Project of Peking University School and Hospital of Stomatology,No. 2013-ZD-03。
文摘BACKGROUND Loss of motor function in the trapezius muscle is one complication of radical neck dissection after cutting the accessory nerve(AN) during surgery.Nerve repair is an effective method to restore trapezius muscle function,and includes neurolysis,direct suture,and nerve grafting.The suprascapular nerve(SCN) and AN are next to each other in position.The function of the AN and SCN in shoulder elevation and abduction movement is synergistic.SCN might be considered by surgeons for AN reanimation.AIM To obtain anatomical and clinical data for partial suprascapular nerve-to-AN transfer.METHODS Ten sides of cadavers perfused with formalin were obtained from the Department of Human Anatomy,Histology and Embryology,Peking University Health Science Center.The SCN(n = 10) and AN(n = 10) were carefully dissected in the posterior triangle of the neck,and the trapezius muscle was dissected to fully display the accessory nerve.The length of the SCN from the origin of the brachial plexus(a point) to the scapular notch(b point) and the distance of the SCN from the origin point(a point) to the point(c point) where the AN entered the border of the trapezius muscle were measured.The length and branches of the AN in the trapezius muscle were measured.A female patient aged 55 years underwent surgery for partial SCN to AN transfer at Department of Oral and Maxillofacial Surgery,Peking University School and Hospital of Stomatology.The patient suffered from recurrent upper gingival cancer.Radical neck dissection was performed on the right side,and the right AN was removed at the intersection between the nerve and the posterior border of the SCM muscle.One-third of the diameter of the SCN was cut off,and combined epineurial and perineurial sutures were applied between the distal end of the cut-off fascicles of the SCN and the proximal end of the AN without tension.Both subjective and objective evaluations were performed before,three months after,and nine months after surgery.For the subjective evaluation,the questionnaire included the Neck Dissection Impairment Index(NDII) and the Constant Shoulder Scale.Electromyography was used for the objective examination.Data were analyzed using t tests with SPSS 19.0 software to determine the relationship between the length of the SCN and the linear distance.A P value of < 0.05 was considered as statistically significant.RESULTS The whole length of the AN in the trapezius muscle was 16.89 cm.The average numbers of branches distributed in the descending,horizontal and ascending portions were 3.8,2.6 and 2.2,respectively.The diameter of the AN was 1.94 mm at the anterior border of the trapezius.The length of the suprascapular nerve from the origin of the brachial plexus to the scapular notch was longer than the distance of the suprascapular nerve from the origin point to the point where the accessory nerve entered the upper edge of the trapezius muscle.The amplitude of trapezius muscle electromyography indicated that both the horizontal and ascending portions of the trapezius muscle on the right side had better function than the left side nine months after surgery.The results showed that the right-sided supraspinatus and infraspinatus muscles did not lose more function than the left side.CONCLUSION Based on anatomical data and clinical application,partial suprascapular nerve-to-AN transfer could be achieved and may improve innervation of the affected trapezius muscle after radical neck dissection.
文摘Dear Editor,Orofacial cleft(OFC),which includes cleft lip and/or palate(CL/P)and cleft palate(CP),is the most common congenital craniofacial structural disorder,with a prevalence of 1.416%。among live infants worldwide(Massenburg et al.,2021).Nonsyndromic OFC(NSOFC),which does not contain other malformations as syndromic OFC(SOFC),accounts for 70%of cases and is believed to have complex etiologies.Notably,it has been established that genetic factors play a crucial role in the occurrence of NSOFC(Dixon et al.,2011).
基金supported by the National Key R&D Program of China[grant number 2018YFE0104200]the National Natural Science Foundation of China[grant numbers 51901003,51931001,52171233,51875310]+1 种基金the Beijing Natural Science Foundation[grant number L212014]the Open Project of NMPA Key Laboratory for Dental Materials[grant number PKUSS20200401].
文摘Additive manufacturing has received attention for the fabrication of medical implants that have customized and complicated structures.Biodegradable Zn metals are revolutionary materials for orthopedic implants.In this study,pure Zn porous scaffolds with diamond structures were fabricated using customized laser powder bed fusion(L-PBF)technology.First,the mechanical properties,corrosion behavior,and biocompatibility of the pure Zn porous scaffolds were characterized in vitro.The scaffolds were then implanted into the rabbit femur critical-size bone defect model for 24 weeks.The results showed that the pure Zn porous scaffolds had compressive strength and rigidity comparable to those of cancellous bone,as well as relatively suitable degradation rates for bone regeneration.A benign host response was observed using hematoxylin and eosin(HE)staining of the heart,liver,spleen,lungs,and kidneys.Moreover,the pure Zn porous scaffold showed good biocompatibility and osteogenic promotion ability in vivo.This study showed that pure Zn porous scaffolds with customized structures fabricated using L-PBF represent a promising biodegradable solution for treating large bone defects.
基金supported by the National Natural Science Foundation of China(Nos.81671006 and 81300894)the CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-038)+2 种基金the National Clinical Key Discipline Construction Project(No.PKUSSNKP-202102)the Program for New Clinical Techniques and Therapies of Peking University Hospital of Stomatology(No.PKUSSNCT-22A14)the Innovation Fund for Outstanding Doctoral Candidates of Peking University Health Science Center(No.BMU2022BSS001),China.
文摘Oral leukoplakia is a common precursor lesion of oral squamous cell carcinoma,which indicates a high potential of malignancy.The malignant transformation of oral leukoplakia seriously affects patient survival and quality of life;however,it is difficult to identify oral leukoplakia patients who will develop carcinoma because no biomarker exists to predict malignant transformation for effective clinical management.As a major problem in the field of head and neck pathologies,it is imperative to identify biomarkers of malignant transformation in oral leukoplakia.In this review,we discuss the potential biomarkers of malignant transformation reported in the literature and explore the translational probabilities from bench to bedside.Although no single biomarker has yet been applied in the clinical setting,profiling for genomic instability might be a promising adjunct.
基金supported by the National Key R&D Program of China(2020YFA0710401)National Natural Science Foundation of China(51972005,51903003,51973226,81871782 and 51672009)the Youth Innovation Promotion Association CAS(No.2019031)for financial support.
文摘Hydrogels are extracellular-matrix-like biomimetic materials that have wide biomedical applications in tissue engineering and drug delivery.However,most hydrogels cannot simultaneously fulfill the mechanical and cell compatibility requirements.In the present study,we prepared a semi-interpenetrating network composite gel(CG)by incorporating short chain chitosan(CS)into a covalent tetra-armed poly(ethylene glycol)network.In addition to satisfying physicochemical,mechanics,biocompatibility,and cell affinity requirements,this CG easily encapsulated acetylsalicylic acid(ASA)via electrostatic interactions and chain entanglement,achieving sustained release for over 14 days and thus promoting periodontal ligament stem cell(PDLSC)proliferation and osteogenic differentiation.In vivo studies corroborated the capacity of PDLSCs and ASA-laden CG to enhance new bone regeneration in situ using a mouse calvarial bone defect model.This might be attributed to PDLSCs and host mesenchymal stem cells expressing monocyte chemoattractant protein-1,which upregulated M2 macrophage recruitment and polarization in situ,indicating its appealing potential in bone tissue engineering.
基金This study was supported by the National Natural Science Foundation of China(Nos.82071124,82002884,and 81772898)Sichuan Science and Technology Program(Nos.2021YFS0194,2021YFH0143,and 2019YFS0361)Science and Technology Program of Chengdu City(No.2019YF0501151SN).
文摘To flourish,cancers greatly depend on their surrounding tumor microenvironment(TME),and cancer-associated fibroblasts(CAFs)in TME are critical for cancer occurrence and progression because of their versatile roles in extracellular matrix remodeling,maintenance of sternness,blood vessel formation,modulation of tumor metabolism,immune response,and promotion of cancer cell proliferation,migration,invasion,and therapeutic resistance.CAFs are highly heterogeneous stromal cells and their crosstalk with cancer cells is mediated by a complex and intricate signaling network consisting of transforming growth factor-beta,phosphoinositide 3-kinase/AKT/mammalian target of rapamycin,mitogen-activated protein kinase,Wnt,Janus kinase/signal transducers and activators of transcription,epidermal growth factor receptor,Hippo,and nuclear factor kappa-light-chain-enhancer of activated B cells,etc.,signaling pathways.These signals in CAFs exhibit their own special characteristics during the cancer progression and have the potential to be targeted for anticancer therapy.Therefore,a comprehensive understanding of these signaling cascades in interactions between cancer cells and CAFs is necessary to fully realize the pivotal roles of CAFs in cancers.Herein,in this review,we will summarize the enormous amounts of findings on the signals mediating crosstalk of CAFs with cancer cells and its related targets or trials.Further,we hypothesize three potential targeting strategies,including,namely,epithelial-mesenchymal common targets,sequential target perturbation,and crosstalk-directed signaling targets,paving the way for CAF-directed or host cell-directed antitumor therapy.
基金the financial support from Beijing Natural Science Foundation(7212135)National Natural Science Foundation of China(NSFC)(11972001,11972002 and 12072001).
文摘Exosomes derived from mesenchymal stem cells(MSCs)have demonstrated regenerative potential for cell-free bone tissue engineering,nevertheless,certain challenges,including the confined therapeutic potency of exosomes and ineffective delivery method,are still persisted.Here,we confirmed that hypoxic precondition could induce enhanced secretion of exosomes from stem cells from human exfoliated deciduous teeth(SHEDs)via comprehensive proteomics analysis,and the corresponding hypoxic exosomes(H-Exo)exhibited superior potential in promoting cellular angiogenesis and osteogenesis via the significant up-regulation in focal adhesion,VEGF signaling pathway,and thyroid hormone synthesis.Then,we developed a platform technology enabling the effective delivery of hypoxic exosomes with sustained release kinetics to irregular-shaped bone defects via injection.This platform is based on a simple adsorbing technique,where exosomes are adsorbed onto the surface of injectable porous poly(lactide-co-glycolide)(PLGA)microspheres with bioinspired polydopamine(PDA)coating(PMS-PDA microspheres).The PMS-PDA microspheres could effectively adsorb exosomes,show sustained release of H-Exo for 21 days with high bioactivity,and induce vascularized bone regeneration in 5-mm rat calvarial defect.These findings indicate that the hypoxic precondition and PMS-PDA porous microsphere-based exosome delivery are efficient in inducing tissue regeneration,hence facilitating the clinical translation of exosome-based therapy.
基金This study was supported by the Innovation research program[HHKT-00-03]the National Natural Science Foundation of China[grant numbers 82170929,81970908,51901003,81200814,and 81771039].
文摘Guided bone regeneration membranes have been effectively applied in oral implantology to repair bone defects.However,typical resorbable membranes composed of collagen(Col)have insufficient mechanical properties and high degradation rate,while non-resorbable membranes need secondary surgery.Herein,we designed a photocrosslinkable collagen/polycaprolactone methacryloyl/magnesium(Col/PCLMA/Mg)composite membrane that provided spatiotemporal support effect after photocrosslinking.Magnesium particles were added to the PCLMA solution and Col/PCLMA and Col/PCLMA/Mg membranes were developed;Col membranes and PCL membranes were used as controls.After photocrosslinking,an interpenetrating polymer network was observed by scanning electron microscopy(SEM)in Col/PCL and Col/PCL/Mg membranes.The elastic modulus,swelling behavior,cytotoxicity,cell attachment,and cell proliferation of the membranes were evaluated.Degradation behavior in vivo and in vitro was monitored according to mass change and by SEM.The membranes were implanted into calvarial bone defects of rats for 8 weeks.The Col/PCL and Col/PCL/Mg membranes displayed much higher elastic modulus(p<0.05),and a lower swelling rate(p<0.05),than Col membranes,and there were no differences in cell biocompatibility among groups(p>0.05).The Col/PCL and Col/PCL/Mg membranes had lower degradation rates than the Col membranes,both in vivo and in vitro(p<0.05).The Col/PCL/Mg groups showed enhanced osteogenic capability compared with the Col groups at week 8(p<0.05).The Col/PCL/Mg composite membrane represents a new strategy to display space maintenance and enhance osteogenic potential,which meets clinical needs.
