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 enviro...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.展开更多
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
The use of robots to augment human capabilities and assist in work has long been an aspiration.Robotics has been developing since the 1960s when the first industrial robot was introduced.As technology has advanced,rob...The use of robots to augment human capabilities and assist in work has long been an aspiration.Robotics has been developing since the 1960s when the first industrial robot was introduced.As technology has advanced,robotic-assisted surgery has shown numerous advantages,including more precision,efficiency,minimal invasiveness,and safety than is possible with conventional techniques,which are research hotspots and cutting-edge trends.This article reviewed the history of medical robot development and seminal research papers about current research progress.Taking the autonomous dental implant robotic system as an example,the advantages and prospects of medical robotic systems would be discussed which would provide a reference for future research.展开更多
Accurate segmentation of oral surgery-related tissues from cone beam computed tomography(CBCT)images can significantly accelerate treatment planning and improve surgical accuracy.In this paper,we propose a fully autom...Accurate segmentation of oral surgery-related tissues from cone beam computed tomography(CBCT)images can significantly accelerate treatment planning and improve surgical accuracy.In this paper,we propose a fully automated tissue segmentation system for dental implant surgery.Specifically,we propose an image preprocessing method based on data distribution histograms,which can adaptively process CBCT images with different parameters.Based on this,we use the bone segmentation network to obtain the segmentation results of alveolar bone,teeth,and maxillary sinus.We use the tooth and mandibular regions as the ROI regions of tooth segmentation and mandibular nerve tube segmentation to achieve the corresponding tasks.The tooth segmentation results can obtain the order information of the dentition.The corresponding experimental results show that our method can achieve higher segmentation accuracy and efficiency compared to existing methods.Its average Dice scores on the tooth,alveolar bone,maxillary sinus,and mandibular canal segmentation tasks were 96.5%,95.4%,93.6%,and 94.8%,respectively.These results demonstrate that it can accelerate the development of digital dentistry.展开更多
BACKGROUND Orthodontic treatment can easily cause local soft tissue reactions in the oral cavity of patients under mechanical stress,leading to oral mucosal ulcers and affecting their quality of life.At present,only l...BACKGROUND Orthodontic treatment can easily cause local soft tissue reactions in the oral cavity of patients under mechanical stress,leading to oral mucosal ulcers and affecting their quality of life.At present,only limited literature has explored the factors leading to oral ulcers in orthodontic treatment,and these research results are still controversial.AIM To investigate the current status and related factors of oral mucosal ulcers during orthodontic treatment,aiming to provide a valuable reference for preventing this disease in clinical practice.METHODS A total of 587 patients who underwent orthodontic treatment at the Peking University School of Stomatology and Hospital of Stomatology between 2020 and 2022 were selected and allocated to an observation or control group according to the incidence of oral mucosal ulcers during orthodontic therapy.A questionnaire survey was constructed to collect patient data,including basic information,lifestyle and eating habits,treatment details,mental factors,and trace element levels,and a comparative analysis of this data was performed between the two groups.RESULTS A logistic regression model with oral ulcers as the dependent variable was established.The regression results showed that age(≥60 years:odds ratio[OR]:6.820;95%confidence interval[CI]:2.226–20.893),smoking history(smoking:OR:4.434;95%CI:2.527–7.782),toothbrush hardness(hard:OR:2.804;95%CI:1.746–4.505),dietary temperature(hot diet:OR:1.399;95%CI:1.220–1.722),treatment course(>1 year:OR:3.830;95%CI:2.203–6.659),and tooth brushing frequency(>1 time per day:OR:0.228;95%CI:0.138–0.377)were independent factors for oral mucosal ulcers(P<0.05).Furthermore,Zn level(OR:0.945;95%CI:0.927–0.964)was a protective factor against oral ulcers,while the SAS(OR:1.284;95%CI:1.197–1.378)and SDS(OR:1.322;95%CI:1.231–1.419)scores were risk factors.CONCLUSION Age≥60 years,smoking history,hard toothbrush,hot diet,treatment course for>1 year,tooth brushing frequency of≤1 time per day,and mental anxiety are independent risk factors for oral mucosal ulcers.Therefore,these factors should receive clinical attention and be incorporated into the development and optimization of preventive strategies for reducing oral ulcer incidence.展开更多
The oral microbiota is a vital part of the human microbiota that functions in various physiological processes and ishighly relevant to cancers and other diseases. With the alterations of host immune competence, the ho...The oral microbiota is a vital part of the human microbiota that functions in various physiological processes and ishighly relevant to cancers and other diseases. With the alterations of host immune competence, the homeostatic balanceexisting between the oral microbiota and host may be disturbed and result in the development of diseases. Numerousobservations have suggested that small RNAs are key regulators of bacterial pathogenesis and bacteria-host interactions.Further, bacterial small RNAs are considered to be promising biomarkers for the development of novel, and efficacioustherapies for oral dysbiosis. Mechanistic insights into how oral pathogens communicate with other bacteria or host cellsin oral cancers via small RNAs are hot topics of research. Current studies also have begun to elucidate the key role oforal microbiota in the development of systemic diseases. This article discusses existing findings and nascent mechanismsgoverning the small RNA-based interactions between oral microbiota and associated diseases. The knowledge of suchinteractions is key in planning approaches to reverse dysbiosis to achieve health.展开更多
The overall health condition of patients significantly affects the diagnosis, treatment, and prognosis of endodontic diseases. Asystemic consideration of the patient’s overall health along with oral conditions holds ...The overall health condition of patients significantly affects the diagnosis, treatment, and prognosis of endodontic diseases. Asystemic consideration of the patient’s overall health along with oral conditions holds the utmost importance in determining thenecessity and feasibility of endodontic therapy, as well as selecting appropriate therapeutic approaches. This expert consensus is acollaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence,aiming to provide general guidance on clinical procedures, improve patient safety and enhance clinical outcomes of endodontictherapy in patients with compromised overall health.展开更多
In this editorial,we offer commentary on the article published by Chen et al in a recent issue of the World Journal of Gastroenterology(2024;30:1346-1357).The study highlights a noteworthy association between persiste...In this editorial,we offer commentary on the article published by Chen et al in a recent issue of the World Journal of Gastroenterology(2024;30:1346-1357).The study highlights a noteworthy association between persistently elevated,yet highnormal levels of alanine transaminase(ALT)and an escalated cumulative risk of developing metabolic dysfunction-associated fatty liver disease(MAFLD).MAFLD has emerged as a globally prevalent chronic liver condition,whose incidence is steadily rising in parallel with improvements in living standards.Left unchecked,MAFLD can progress from hepatic steatosis to liver fibrosis,cirrhosis,and even hepatocellular carcinoma,underscoring the importance of early screening and diagnosis.ALT is widely recognized as a reliable biomarker for assessing the extent of hepatocellular damage.While ALT levels demonstrate a significant correlation with the severity of fatty liver disease,they lack specificity.The article by Chen et al contributes to our understanding of the development of MAFLD by investigating the long-term implications of high-normal ALT levels.Their findings suggest that sustained elevation within the normal range is linked to an increased likelihood of developing MAFLD,emphasizing the need for closer monitoring and potential intervention in such cases.展开更多
Autophagy is a widespread biological process that controls cellular growth,survival,development,and death.Circadian rhythm is a recurring reaction of living organisms and behaviors to variations in surrounding brightn...Autophagy is a widespread biological process that controls cellular growth,survival,development,and death.Circadian rhythm is a recurring reaction of living organisms and behaviors to variations in surrounding brightness and obscurity.Most of the fundamental physiological processes in mammals,such as the sleep-wake pattern and the rhythm of nutrition and energy metabolism,are governed by circadian rhythms.Research has indicated that autophagy exhibits a specific circadian pattern in both normal and abnormal conditions.Autophagy can modulate circadian rhythms by breaking down proteins that regulate the circadian clock.The potential regulatory connection between the two has been a popular subject of clinical and fundamental research.Understanding the interaction between circadian rhythm and autophagy could potentially lead to the development of novel approaches for disease treatment in the future.The present analysis presented a summary of the molecular processes implicated in the interplay between autophagy and circadian rhythm,as well as the pathological importance of the disrupted regulatory association between these two phenomena.展开更多
With recent developments in photosensitizers and light delivery systems,topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) has become the fourth alternative therapeutic approach in the management of...With recent developments in photosensitizers and light delivery systems,topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) has become the fourth alternative therapeutic approach in the management of oral leucoplakia (OLK) due to its minimally invasive nature,efficacy,and low risk of systemic side effects and disfigurement.This report presents step-by-step guidelines for applying topical ALA-PDT in the management of OLK based on both the clinical experience of the authors and a systematic review of the current literature.Studies using protocols with standardized parameters and randomized clinical trials at multiple centres with adequate sample sizes and both interim and long-term follow-ups are needed before universally applicable guidelines can be produced in this field.展开更多
Chronic kidney disease （CKD） is a worldwide public health problem that is growing in prevalence and is associated with severe complications. During the progression of the disease, a majority of CKD patients suffer o...Chronic kidney disease （CKD） is a worldwide public health problem that is growing in prevalence and is associated with severe complications. During the progression of the disease, a majority of CKD patients suffer oral complications. Dental implants are currently the most reliable and successful treatment for missing teeth. However, due to complications of CKD such as infections, bone lesions, bleeding risks, and altered drug metabolism, dental implant treatment for renal failure patients on dialysis is more challenging. In this review, we have summarized the characteristics of CKD and previous publications regarding dental treatments for renal failure patients. In addition, we discuss our recent research results and clinical experience in order to provide dental implant practitioners with a clinical guideline for dental implant treatment for renal failure patients undergoing hemodialysis.展开更多
For more than 20 years,researchers have isolated and identified postnatal dental pulp stem cells(DPSCs)from different teeth,including natal teeth,exfoliated deciduous teeth,healthy teeth,and diseased teeth.Their mesen...For more than 20 years,researchers have isolated and identified postnatal dental pulp stem cells(DPSCs)from different teeth,including natal teeth,exfoliated deciduous teeth,healthy teeth,and diseased teeth.Their mesenchymal stem cell(MSC)-like immunophenotypic characteristics,high proliferation rate,potential for multidirectional differentiation and biological features were demonstrated to be superior to those of bone marrow MSCs.In addition,several main application forms of DPSCs and their derivatives have been investigated,including stem cell injections,modified stem cells,stem cell sheets and stem cell spheroids.In vitro and in vivo administration of DPSCs and their derivatives exhibited beneficial effects in various disease models of different tissues and organs.Therefore,DPSCs and their derivatives are regarded as excellent candidates for stem cell-based tissue regeneration.In this review,we aim to provide an overview of the potential application of DPSCs and their derivatives in the field of regenerative medicine.We describe the similarities and differences of DPSCs isolated from donors of different ages and health conditions.The methodologies for therapeutic administration of DPSCs and their derivatives are introduced,including single injections and the transplantation of the cells with a support,as cell sheets,or as cell spheroids.We also summarize the underlying mechanisms of the regenerative potential of DPSCs.展开更多
BACKGROUND The conventional implant approach involves flap elevation,which may result in increased soft tissue and bone loss and postoperative morbidity.The flapless surgical technique,aided by three-dimensional medic...BACKGROUND The conventional implant approach involves flap elevation,which may result in increased soft tissue and bone loss and postoperative morbidity.The flapless surgical technique,aided by three-dimensional medical imaging equipment,is regarded as a possible alternative to the conventional approach to alleviate the above issues.Several studies have been performed regarding the role of flapless implant surgery.However,the results are inconsistent and there is no robust synthesis of long-term evidence to better inform surgeons regarding which type of surgical technique is more beneficial to the long-term prognosis of patients in need of implant insertion.AIM To compare the long-term clinical performance after flapless implant surgery to that after the conventional approach with flap elevation.METHODS PubMed,EMBASE,Cochrane Central Register of Controlled Trials,and grey literature databases were searched from inception to 23 September 2019.Randomised controlled trials (RCTs) and cohort studies comparing the long-term clinical performance after flapless implant surgery to that after the conventional approach over a follow-up of three years or more were induded.Meta-analyses were conducted to estimate the odds ratios (ORs) or mean differences (MDs) and their 95 To confidence intervals (CIs) between the long-term implant survival rate,marginal bone loss,and complication rate of the flapless and conventional groups.Subgroup analyses were carried out to account for the possible effects of the guided or free-hand method during flapless surgery.RESULTS Ten articles,including four RCTs and six cohort studies,satisfied the eligibility criteria and nine of them were inclded in the meta-analysis.There was no significant difference between the long-term implant survival rate [OR=1.30,95%CI (0.37,4.54),P=0.68],marginal bone loss [MD=0.01,95%CI (-0.42,0.44),P=0.97],and complication rate [OR=1.44,95%CI (0.77,2.68),P=0.25] after flapless implant surgery and the conventional approach.Moreover,subgroup analyses revealed that there was no statistically significant difference between the implant survival rate [guided:OR=1.52,95%CI (0.19,12.35),P=0.70];free-hand:n=1,could not be estimated),marginal bone loss [guided:MD=0.22,95%CI (-0.14,0.59),P=0.23;free-hand:MD=-0.27,95%CI (-1.10,0.57),P=0.53],or complication rate [guided:OR=1.16,95%CI (0.52,2.63),P=0.71;free-hand:OR=1.75,95%CI(0.66,4.63),P=0.26] in the flapless and conventional groups either with use of the surgical guide or by the free-hand method.CONCLUSION The flapless surgery and conventional approach had comparable clinical performance over three years or more.The guided or free-hand technique does not significantly affect the long-term outcomes of flapless surgery.展开更多
Cell transplantation therapy has certain limitations including immune rejection and limited cell viability,which seriously hinder the transformation of stem cellbased tissue regeneration into clinical practice.Extrace...Cell transplantation therapy has certain limitations including immune rejection and limited cell viability,which seriously hinder the transformation of stem cellbased tissue regeneration into clinical practice.Extracellular vesicles(EVs)not only possess the advantages of its derived cells,but also can avoid the risks of cell transplantation.EVs are intelligent and controllable biomaterials that can participate in a variety of physiological and pathological activities,tissue repair and regeneration by transmitting a variety of biological signals,showing great potential in cell-free tissue regeneration.In this review,we summarized the origins and characteristics of EVs,introduced the pivotal role of EVs in diverse tissues regeneration,discussed the underlying mechanisms,prospects,and challenges of EVs.We also pointed out the problems that need to be solved,application directions,and prospects of EVs in the future and shed new light on the novel cell-free strategy for using EVs in the field of regenerative medicine.展开更多
Dental resin composites(DRCs)are popular materials for repairing caries or dental defect,requiring excellent properties to cope with the complex oral environment.Filler/resin interface interaction has a significant im...Dental resin composites(DRCs)are popular materials for repairing caries or dental defect,requiring excellent properties to cope with the complex oral environment.Filler/resin interface interaction has a significant impact on the physicochemical/biological properties and service life of DRCs.展开更多
Objective:To elucidate whether DNA aneuploidy was an independent discriminator for carcinoma within oral potentially malignant disorders(OPMDs),and further establish and validate a risk model based on DNA aneuploidy f...Objective:To elucidate whether DNA aneuploidy was an independent discriminator for carcinoma within oral potentially malignant disorders(OPMDs),and further establish and validate a risk model based on DNA aneuploidy for the detection of oral cancer.Methods:A total of 810 consecutive patients with OPMD were prospectively enrolled from March 2013 to December 2018,and divided into a training set(n=608)and a test set(n=202).Brushing and biopsy samples from each patient were processed by DNADNA image cytometry and histopathological examination,respectively.Results:DNA aneuploidy of an outside DNA index≥3.5 in OPMD was an independent marker strongly associated with malignant risk[adjusted odds ratio:13.04;95%confidence interval(CI):5.46-31.14].In the training and test sets,the area under the curve(AUC)was 0.87(95%CI:0.82-0.91)and 0.77(95%CI:0.57-0.97),respectively,for detecting carcinoma in OPMD patients.The independent risk factors of lateral/ventral tongue and non-homogenous type combined with a risk model built with a multivariate logistic regression revealed a more favorable diagnostic efficacy associated with the training set(AUC:0.93;95%CI:0.91-0.96)and test set(AUC:0.94;95%CI:0.90-0.98).The sensitivity and specificity of carcinoma detection within OPMD was improved to 100%and 88.1%,respectively.Conclusions:This large-scale diagnostic study established a risk model based on DNA aneuploidy that consisted of a noninvasive strategy with lateral/ventral tongue and non-homogenous features.The results showed favorable diagnostic efficacy for detecting carcinoma within OPMD,irrespective of the clinical and pathological diagnoses of OPMD.Multicenter validation and longitudinal studies are warranted to evaluate community practices and clinical applications.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
Cancer is a major threat to human life worldwide. Traditional cancer treatments, such as chemotherapy and surgery, have major limitations and can cause irreversible damage to normal tissues while killing the cancer ce...Cancer is a major threat to human life worldwide. Traditional cancer treatments, such as chemotherapy and surgery, have major limitations and can cause irreversible damage to normal tissues while killing the cancer cells. Magnesium(Mg) alloys are widely reported novel potential biomedical materials with acceptable mechanical properties and good osteogenic and angiogenic properties. In this review, we summarize the Mg alloys for antitumor applications, including pure Mg and Mg alloys(Mg-Ag, Mg-Gd, Mg-Li-Zn, Mg-Ca-Sr-Zn, et al.) fabricated by casting and extruding, selective laser melting methods. Mg alloys can exhibit antitumor effect on bone tumor, breast cancer, and liver tumor,etal. What's more, after tumor tissue is eliminated, Mg alloys prevent tumor recurrence, fill tissue defects and promote tissue regeneration.The antitumor effects of Mg alloys are mainly due to their degradation products. Overall, Mg alloys show great potential in tumor treatments due to the dual function of antitumor and tissue regeneration.展开更多
Cancer cell membrane(CCM)derived nanotechnology functionalizes nanoparticles(NPs)to recognize homologous cells,exhibiting translational potential in accurate tumor therapy.However,these nanoplatforms are majorly gener...Cancer cell membrane(CCM)derived nanotechnology functionalizes nanoparticles(NPs)to recognize homologous cells,exhibiting translational potential in accurate tumor therapy.However,these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts(CDX),ignoring the tumor heterogeneity and differentiation from inter-and intra-individuals and microenvironments between heterotopic-and orthotopic-tumors,limiting the therapeutic efficiency of such nanoplatforms.Herein,various biomimetic nanoplatforms(CCM-modified gold@Carbon,i.e.,Au@C-CCM)were fabricated by coating CCMs of head and neck squamous cell carcinoma(HNSCC)cell lines and patient-derived cells on the surface of Au@C NP.The generated Au@C-CCMs were evaluated on corresponding CDX,tongue orthotopic xenograft(TOX),immunecompetent primary and distant tumor models,and patient-derived xenograft(PDX)models.The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death.The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency,far above those with mismatched CCMs,resulting in distinct tumor ablation and tumor growth inhibition in all four models.This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC,can be further extended to other malignant tumors therapy.展开更多
A growing number of studies have demonstrated that repeated exposure to sevoflurane during development results in persistent social abnormalities and cognitive impairment.Davunetide,an active fragment of the activity-...A growing number of studies have demonstrated that repeated exposure to sevoflurane during development results in persistent social abnormalities and cognitive impairment.Davunetide,an active fragment of the activity-dependent neuroprotective protein(ADNP),has been implicated in social and cognitive protection.However,the potential of davunetide to attenuate social deficits following sevoflurane exposure and the underlying developmental mechanisms remain poorly understood.In this study,ribosome and proteome profiles were analyzed to investigate the molecular basis of sevoflurane-induced social deficits in neonatal mice.The neuropathological basis was also explored using Golgi staining,morphological analysis,western blotting,electrophysiological analysis,and behavioral analysis.Results indicated that ADNP was significantly down-regulated following developmental exposure to sevoflurane.In adulthood,anterior cingulate cortex(ACC)neurons exposed to sevoflurane exhibited a decrease in dendrite number,total dendrite length,and spine density.Furthermore,the expression levels of Homer,PSD95,synaptophysin,and vglut2 were significantly reduced in the sevoflurane group.Patch-clamp recordings indicated reductions in both the frequency and amplitude of miniature excitatory postsynaptic currents(mEPSCs).Notably,davunetide significantly ameliorated the synaptic defects,social behavior deficits,and cognitive impairments induced by sevoflurane.Mechanistic analysis revealed that loss of ADNP led to dysregulation of Ca^(2+)activity via the Wnt/β-catenin signaling,resulting in decreased expression of synaptic proteins.Suppression of Wnt signaling was restored in the davunetide-treated group.Thus,ADNP was identified as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general anesthetics.This study provides important insights into the mechanisms underlying social and cognitive disturbances caused by sevoflurane exposure in neonatal mice and elucidates the regulatory pathways involved.展开更多
基金supported by the Natural Science Foundation of China (82002851)funding of postdoctoral of Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine+2 种基金fundamental research program funding of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine (JYZZ180)funding of academician workstation in HainanShanghai Anticancer Association EYAS PROJECT (SACA-CY21A01)。
文摘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.
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 number 81970987].
文摘The use of robots to augment human capabilities and assist in work has long been an aspiration.Robotics has been developing since the 1960s when the first industrial robot was introduced.As technology has advanced,robotic-assisted surgery has shown numerous advantages,including more precision,efficiency,minimal invasiveness,and safety than is possible with conventional techniques,which are research hotspots and cutting-edge trends.This article reviewed the history of medical robot development and seminal research papers about current research progress.Taking the autonomous dental implant robotic system as an example,the advantages and prospects of medical robotic systems would be discussed which would provide a reference for future research.
基金supported by National Natural Science Foundation of China(No.81970987).
文摘Accurate segmentation of oral surgery-related tissues from cone beam computed tomography(CBCT)images can significantly accelerate treatment planning and improve surgical accuracy.In this paper,we propose a fully automated tissue segmentation system for dental implant surgery.Specifically,we propose an image preprocessing method based on data distribution histograms,which can adaptively process CBCT images with different parameters.Based on this,we use the bone segmentation network to obtain the segmentation results of alveolar bone,teeth,and maxillary sinus.We use the tooth and mandibular regions as the ROI regions of tooth segmentation and mandibular nerve tube segmentation to achieve the corresponding tasks.The tooth segmentation results can obtain the order information of the dentition.The corresponding experimental results show that our method can achieve higher segmentation accuracy and efficiency compared to existing methods.Its average Dice scores on the tooth,alveolar bone,maxillary sinus,and mandibular canal segmentation tasks were 96.5%,95.4%,93.6%,and 94.8%,respectively.These results demonstrate that it can accelerate the development of digital dentistry.
文摘BACKGROUND Orthodontic treatment can easily cause local soft tissue reactions in the oral cavity of patients under mechanical stress,leading to oral mucosal ulcers and affecting their quality of life.At present,only limited literature has explored the factors leading to oral ulcers in orthodontic treatment,and these research results are still controversial.AIM To investigate the current status and related factors of oral mucosal ulcers during orthodontic treatment,aiming to provide a valuable reference for preventing this disease in clinical practice.METHODS A total of 587 patients who underwent orthodontic treatment at the Peking University School of Stomatology and Hospital of Stomatology between 2020 and 2022 were selected and allocated to an observation or control group according to the incidence of oral mucosal ulcers during orthodontic therapy.A questionnaire survey was constructed to collect patient data,including basic information,lifestyle and eating habits,treatment details,mental factors,and trace element levels,and a comparative analysis of this data was performed between the two groups.RESULTS A logistic regression model with oral ulcers as the dependent variable was established.The regression results showed that age(≥60 years:odds ratio[OR]:6.820;95%confidence interval[CI]:2.226–20.893),smoking history(smoking:OR:4.434;95%CI:2.527–7.782),toothbrush hardness(hard:OR:2.804;95%CI:1.746–4.505),dietary temperature(hot diet:OR:1.399;95%CI:1.220–1.722),treatment course(>1 year:OR:3.830;95%CI:2.203–6.659),and tooth brushing frequency(>1 time per day:OR:0.228;95%CI:0.138–0.377)were independent factors for oral mucosal ulcers(P<0.05).Furthermore,Zn level(OR:0.945;95%CI:0.927–0.964)was a protective factor against oral ulcers,while the SAS(OR:1.284;95%CI:1.197–1.378)and SDS(OR:1.322;95%CI:1.231–1.419)scores were risk factors.CONCLUSION Age≥60 years,smoking history,hard toothbrush,hot diet,treatment course for>1 year,tooth brushing frequency of≤1 time per day,and mental anxiety are independent risk factors for oral mucosal ulcers.Therefore,these factors should receive clinical attention and be incorporated into the development and optimization of preventive strategies for reducing oral ulcer incidence.
基金supported by the National Natural Science Foundation of China(Nos.82071104 and 81900988)the Clinical Research Program of 9th People’s Hospital,Shanghai Jiao Tong University School of Medicine(No.JYLJ201908).
文摘The oral microbiota is a vital part of the human microbiota that functions in various physiological processes and ishighly relevant to cancers and other diseases. With the alterations of host immune competence, the homeostatic balanceexisting between the oral microbiota and host may be disturbed and result in the development of diseases. Numerousobservations have suggested that small RNAs are key regulators of bacterial pathogenesis and bacteria-host interactions.Further, bacterial small RNAs are considered to be promising biomarkers for the development of novel, and efficacioustherapies for oral dysbiosis. Mechanistic insights into how oral pathogens communicate with other bacteria or host cellsin oral cancers via small RNAs are hot topics of research. Current studies also have begun to elucidate the key role oforal microbiota in the development of systemic diseases. This article discusses existing findings and nascent mechanismsgoverning the small RNA-based interactions between oral microbiota and associated diseases. The knowledge of suchinteractions is key in planning approaches to reverse dysbiosis to achieve health.
基金supported by the National Natural Science Foundation of China(82370947)the Natural Science Foundation of Sichuan Province(2023NSFSC1505)。
文摘The overall health condition of patients significantly affects the diagnosis, treatment, and prognosis of endodontic diseases. Asystemic consideration of the patient’s overall health along with oral conditions holds the utmost importance in determining thenecessity and feasibility of endodontic therapy, as well as selecting appropriate therapeutic approaches. This expert consensus is acollaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence,aiming to provide general guidance on clinical procedures, improve patient safety and enhance clinical outcomes of endodontictherapy in patients with compromised overall health.
基金Supported by the Natural Science Foundation of Sichuan Province,No.24NSFSC0163State Key Clinical Department of Oral&Maxillofacial Surgery。
文摘In this editorial,we offer commentary on the article published by Chen et al in a recent issue of the World Journal of Gastroenterology(2024;30:1346-1357).The study highlights a noteworthy association between persistently elevated,yet highnormal levels of alanine transaminase(ALT)and an escalated cumulative risk of developing metabolic dysfunction-associated fatty liver disease(MAFLD).MAFLD has emerged as a globally prevalent chronic liver condition,whose incidence is steadily rising in parallel with improvements in living standards.Left unchecked,MAFLD can progress from hepatic steatosis to liver fibrosis,cirrhosis,and even hepatocellular carcinoma,underscoring the importance of early screening and diagnosis.ALT is widely recognized as a reliable biomarker for assessing the extent of hepatocellular damage.While ALT levels demonstrate a significant correlation with the severity of fatty liver disease,they lack specificity.The article by Chen et al contributes to our understanding of the development of MAFLD by investigating the long-term implications of high-normal ALT levels.Their findings suggest that sustained elevation within the normal range is linked to an increased likelihood of developing MAFLD,emphasizing the need for closer monitoring and potential intervention in such cases.
基金funded by the National Natural Science Foundation of China(Code No.82100954/81800924)Natural Science Foundation of Inner Mongolia Autonomous Region(Code No.2023QN08026)+3 种基金Key Research and Development Projects of Shaanxi Province(Code No.2022KW-12)The Basic and Natural Science Research Program of Shaanxi Province(Code No.2022JQ-915)Key Research and Development Program of Tibet Autonomous Region(XZ202001ZY0059G)New Technology and New Business Project of the Third Affiliated Hospital of Air Force Military Medical University(Code No.LX2021-416).
文摘Autophagy is a widespread biological process that controls cellular growth,survival,development,and death.Circadian rhythm is a recurring reaction of living organisms and behaviors to variations in surrounding brightness and obscurity.Most of the fundamental physiological processes in mammals,such as the sleep-wake pattern and the rhythm of nutrition and energy metabolism,are governed by circadian rhythms.Research has indicated that autophagy exhibits a specific circadian pattern in both normal and abnormal conditions.Autophagy can modulate circadian rhythms by breaking down proteins that regulate the circadian clock.The potential regulatory connection between the two has been a popular subject of clinical and fundamental research.Understanding the interaction between circadian rhythm and autophagy could potentially lead to the development of novel approaches for disease treatment in the future.The present analysis presented a summary of the molecular processes implicated in the interplay between autophagy and circadian rhythm,as well as the pathological importance of the disrupted regulatory association between these two phenomena.
基金supported by grants from the National Natural Science Foundation of China (81572663, 81621062, 81730030, 81771081 and 81520108009)the 111 Project of MOE (B14038), Chinathe National Health Planning Commission of China (201502018)
文摘With recent developments in photosensitizers and light delivery systems,topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) has become the fourth alternative therapeutic approach in the management of oral leucoplakia (OLK) due to its minimally invasive nature,efficacy,and low risk of systemic side effects and disfigurement.This report presents step-by-step guidelines for applying topical ALA-PDT in the management of OLK based on both the clinical experience of the authors and a systematic review of the current literature.Studies using protocols with standardized parameters and randomized clinical trials at multiple centres with adequate sample sizes and both interim and long-term follow-ups are needed before universally applicable guidelines can be produced in this field.
基金supported by grants from the National Natural Science Foundation of China(NSFC 81371173)the State Key Laboratory of Oral Diseases(SKLOD201704)+1 种基金the International Team for Implantology(Grant No.975_2014,Basel,Switzerland)the National Key R&D Program of China during the thirteenth Five-Year Plan(2016YFC1102700)
文摘Chronic kidney disease （CKD） is a worldwide public health problem that is growing in prevalence and is associated with severe complications. During the progression of the disease, a majority of CKD patients suffer oral complications. Dental implants are currently the most reliable and successful treatment for missing teeth. However, due to complications of CKD such as infections, bone lesions, bleeding risks, and altered drug metabolism, dental implant treatment for renal failure patients on dialysis is more challenging. In this review, we have summarized the characteristics of CKD and previous publications regarding dental treatments for renal failure patients. In addition, we discuss our recent research results and clinical experience in order to provide dental implant practitioners with a clinical guideline for dental implant treatment for renal failure patients undergoing hemodialysis.
基金Supported by National Natural Science Foundation of China,No. U21A20369Sichuan Science and Technology Program,No. 2021YJ0147Research and Develop Program,West China Hospital of Stomatology Sichuan University,No. RD-02-202113
文摘For more than 20 years,researchers have isolated and identified postnatal dental pulp stem cells(DPSCs)from different teeth,including natal teeth,exfoliated deciduous teeth,healthy teeth,and diseased teeth.Their mesenchymal stem cell(MSC)-like immunophenotypic characteristics,high proliferation rate,potential for multidirectional differentiation and biological features were demonstrated to be superior to those of bone marrow MSCs.In addition,several main application forms of DPSCs and their derivatives have been investigated,including stem cell injections,modified stem cells,stem cell sheets and stem cell spheroids.In vitro and in vivo administration of DPSCs and their derivatives exhibited beneficial effects in various disease models of different tissues and organs.Therefore,DPSCs and their derivatives are regarded as excellent candidates for stem cell-based tissue regeneration.In this review,we aim to provide an overview of the potential application of DPSCs and their derivatives in the field of regenerative medicine.We describe the similarities and differences of DPSCs isolated from donors of different ages and health conditions.The methodologies for therapeutic administration of DPSCs and their derivatives are introduced,including single injections and the transplantation of the cells with a support,as cell sheets,or as cell spheroids.We also summarize the underlying mechanisms of the regenerative potential of DPSCs.
基金the Graduate Student's Research and Innovation Fund of Sichuan University,No.2018YJSY108the China Postdoctoral Science Foundation Funded Project,No.2018M640931+1 种基金the Science and Technology Key Research and Development Program of Sichuan Province,No.2019YFS0142the National Natural Science Foundation of China,No.81901060.
文摘BACKGROUND The conventional implant approach involves flap elevation,which may result in increased soft tissue and bone loss and postoperative morbidity.The flapless surgical technique,aided by three-dimensional medical imaging equipment,is regarded as a possible alternative to the conventional approach to alleviate the above issues.Several studies have been performed regarding the role of flapless implant surgery.However,the results are inconsistent and there is no robust synthesis of long-term evidence to better inform surgeons regarding which type of surgical technique is more beneficial to the long-term prognosis of patients in need of implant insertion.AIM To compare the long-term clinical performance after flapless implant surgery to that after the conventional approach with flap elevation.METHODS PubMed,EMBASE,Cochrane Central Register of Controlled Trials,and grey literature databases were searched from inception to 23 September 2019.Randomised controlled trials (RCTs) and cohort studies comparing the long-term clinical performance after flapless implant surgery to that after the conventional approach over a follow-up of three years or more were induded.Meta-analyses were conducted to estimate the odds ratios (ORs) or mean differences (MDs) and their 95 To confidence intervals (CIs) between the long-term implant survival rate,marginal bone loss,and complication rate of the flapless and conventional groups.Subgroup analyses were carried out to account for the possible effects of the guided or free-hand method during flapless surgery.RESULTS Ten articles,including four RCTs and six cohort studies,satisfied the eligibility criteria and nine of them were inclded in the meta-analysis.There was no significant difference between the long-term implant survival rate [OR=1.30,95%CI (0.37,4.54),P=0.68],marginal bone loss [MD=0.01,95%CI (-0.42,0.44),P=0.97],and complication rate [OR=1.44,95%CI (0.77,2.68),P=0.25] after flapless implant surgery and the conventional approach.Moreover,subgroup analyses revealed that there was no statistically significant difference between the implant survival rate [guided:OR=1.52,95%CI (0.19,12.35),P=0.70];free-hand:n=1,could not be estimated),marginal bone loss [guided:MD=0.22,95%CI (-0.14,0.59),P=0.23;free-hand:MD=-0.27,95%CI (-1.10,0.57),P=0.53],or complication rate [guided:OR=1.16,95%CI (0.52,2.63),P=0.71;free-hand:OR=1.75,95%CI(0.66,4.63),P=0.26] in the flapless and conventional groups either with use of the surgical guide or by the free-hand method.CONCLUSION The flapless surgery and conventional approach had comparable clinical performance over three years or more.The guided or free-hand technique does not significantly affect the long-term outcomes of flapless surgery.
基金Supported by The Interdisciplinary and Intercollege Research Project of the State Key Laboratory of Oral Disease,Sichuan University,No.2021KXK0403Health Commission of Sichuan Province,No.21PJ062。
文摘Cell transplantation therapy has certain limitations including immune rejection and limited cell viability,which seriously hinder the transformation of stem cellbased tissue regeneration into clinical practice.Extracellular vesicles(EVs)not only possess the advantages of its derived cells,but also can avoid the risks of cell transplantation.EVs are intelligent and controllable biomaterials that can participate in a variety of physiological and pathological activities,tissue repair and regeneration by transmitting a variety of biological signals,showing great potential in cell-free tissue regeneration.In this review,we summarized the origins and characteristics of EVs,introduced the pivotal role of EVs in diverse tissues regeneration,discussed the underlying mechanisms,prospects,and challenges of EVs.We also pointed out the problems that need to be solved,application directions,and prospects of EVs in the future and shed new light on the novel cell-free strategy for using EVs in the field of regenerative medicine.
基金the support from the National Natural Science Foundation of China(Grant nos.81921002,82201115)China Postdoctoral Science Foundation(no.2021M702166)the Innovative Research Team of High-level Local Universities in Shanghai,Oral and Maxillofacial Regeneration and Functional Restoration。
文摘Dental resin composites(DRCs)are popular materials for repairing caries or dental defect,requiring excellent properties to cope with the complex oral environment.Filler/resin interface interaction has a significant impact on the physicochemical/biological properties and service life of DRCs.
基金supported by the National Natural Science Foundation of China(Grant No.82074502)the Science and Technology Commission of Shanghai Municipality(Grant No.20Y11903700)+3 种基金the Shanghai Hospital Development Center(Grant No.SHDC2020CR4082)the Shanghai Municipal Health Committee(Grant No.202040457)the Innovative Research Team of High-level Local Universities in Shanghai(Grant No.SSMU-ZDCX20180901)the SHIPM-mu Fund from the Shanghai Institute of Precision Medicine(Grant No.JC201807)。
文摘Objective:To elucidate whether DNA aneuploidy was an independent discriminator for carcinoma within oral potentially malignant disorders(OPMDs),and further establish and validate a risk model based on DNA aneuploidy for the detection of oral cancer.Methods:A total of 810 consecutive patients with OPMD were prospectively enrolled from March 2013 to December 2018,and divided into a training set(n=608)and a test set(n=202).Brushing and biopsy samples from each patient were processed by DNADNA image cytometry and histopathological examination,respectively.Results:DNA aneuploidy of an outside DNA index≥3.5 in OPMD was an independent marker strongly associated with malignant risk[adjusted odds ratio:13.04;95%confidence interval(CI):5.46-31.14].In the training and test sets,the area under the curve(AUC)was 0.87(95%CI:0.82-0.91)and 0.77(95%CI:0.57-0.97),respectively,for detecting carcinoma in OPMD patients.The independent risk factors of lateral/ventral tongue and non-homogenous type combined with a risk model built with a multivariate logistic regression revealed a more favorable diagnostic efficacy associated with the training set(AUC:0.93;95%CI:0.91-0.96)and test set(AUC:0.94;95%CI:0.90-0.98).The sensitivity and specificity of carcinoma detection within OPMD was improved to 100%and 88.1%,respectively.Conclusions:This large-scale diagnostic study established a risk model based on DNA aneuploidy that consisted of a noninvasive strategy with lateral/ventral tongue and non-homogenous features.The results showed favorable diagnostic efficacy for detecting carcinoma within OPMD,irrespective of the clinical and pathological diagnoses of OPMD.Multicenter validation and longitudinal studies are warranted to evaluate community practices and clinical applications.
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supported by the National Key R&D Program of China [grant number 2021YFC2400700]the National Natural Science Foundation of China [grant numbers 82170929,81970908]the Beijing Natural Science Foundation [L222090,L222030]。
文摘Cancer is a major threat to human life worldwide. Traditional cancer treatments, such as chemotherapy and surgery, have major limitations and can cause irreversible damage to normal tissues while killing the cancer cells. Magnesium(Mg) alloys are widely reported novel potential biomedical materials with acceptable mechanical properties and good osteogenic and angiogenic properties. In this review, we summarize the Mg alloys for antitumor applications, including pure Mg and Mg alloys(Mg-Ag, Mg-Gd, Mg-Li-Zn, Mg-Ca-Sr-Zn, et al.) fabricated by casting and extruding, selective laser melting methods. Mg alloys can exhibit antitumor effect on bone tumor, breast cancer, and liver tumor,etal. What's more, after tumor tissue is eliminated, Mg alloys prevent tumor recurrence, fill tissue defects and promote tissue regeneration.The antitumor effects of Mg alloys are mainly due to their degradation products. Overall, Mg alloys show great potential in tumor treatments due to the dual function of antitumor and tissue regeneration.
基金funded by The National Natural Science Foundation of China(81872199)Key Program of National Natural Science Foundation of China(82030085)+4 种基金The National Key Research and Development Program of China(2017YFC0908500)The National Natural Science Foundation of China(82002853)China Postdoctoral Science Foundation(2019M661565)Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZLCX20212300,SSMU-ZLCX20180500)funded by“Shuguang Program”supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission(19SG13)。
文摘Cancer cell membrane(CCM)derived nanotechnology functionalizes nanoparticles(NPs)to recognize homologous cells,exhibiting translational potential in accurate tumor therapy.However,these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts(CDX),ignoring the tumor heterogeneity and differentiation from inter-and intra-individuals and microenvironments between heterotopic-and orthotopic-tumors,limiting the therapeutic efficiency of such nanoplatforms.Herein,various biomimetic nanoplatforms(CCM-modified gold@Carbon,i.e.,Au@C-CCM)were fabricated by coating CCMs of head and neck squamous cell carcinoma(HNSCC)cell lines and patient-derived cells on the surface of Au@C NP.The generated Au@C-CCMs were evaluated on corresponding CDX,tongue orthotopic xenograft(TOX),immunecompetent primary and distant tumor models,and patient-derived xenograft(PDX)models.The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death.The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency,far above those with mismatched CCMs,resulting in distinct tumor ablation and tumor growth inhibition in all four models.This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC,can be further extended to other malignant tumors therapy.
基金supported by the National Natural Science Foundation of China(82171170,81971076,82371277 to H.Z.,82101345 to L.R.L.)。
文摘A growing number of studies have demonstrated that repeated exposure to sevoflurane during development results in persistent social abnormalities and cognitive impairment.Davunetide,an active fragment of the activity-dependent neuroprotective protein(ADNP),has been implicated in social and cognitive protection.However,the potential of davunetide to attenuate social deficits following sevoflurane exposure and the underlying developmental mechanisms remain poorly understood.In this study,ribosome and proteome profiles were analyzed to investigate the molecular basis of sevoflurane-induced social deficits in neonatal mice.The neuropathological basis was also explored using Golgi staining,morphological analysis,western blotting,electrophysiological analysis,and behavioral analysis.Results indicated that ADNP was significantly down-regulated following developmental exposure to sevoflurane.In adulthood,anterior cingulate cortex(ACC)neurons exposed to sevoflurane exhibited a decrease in dendrite number,total dendrite length,and spine density.Furthermore,the expression levels of Homer,PSD95,synaptophysin,and vglut2 were significantly reduced in the sevoflurane group.Patch-clamp recordings indicated reductions in both the frequency and amplitude of miniature excitatory postsynaptic currents(mEPSCs).Notably,davunetide significantly ameliorated the synaptic defects,social behavior deficits,and cognitive impairments induced by sevoflurane.Mechanistic analysis revealed that loss of ADNP led to dysregulation of Ca^(2+)activity via the Wnt/β-catenin signaling,resulting in decreased expression of synaptic proteins.Suppression of Wnt signaling was restored in the davunetide-treated group.Thus,ADNP was identified as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general anesthetics.This study provides important insights into the mechanisms underlying social and cognitive disturbances caused by sevoflurane exposure in neonatal mice and elucidates the regulatory pathways involved.
