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

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.

Prognostic significance of SOX2 for chemotherapeutic patients with oral squamous cell carcinoma

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.

Photodynamic therapy guidelines for the management of oral leucoplakia

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.

Dental implant treatment for renal failure patients on dialysis:a clinical guideline

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.

Therapeutic potential of dental pulp stem cells and their derivatives:Insights from basic research toward clinical applications

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.

Long-term clinical performance of flapless implant surgery compared to the conventional approach with flap elevation:A systematic review and meta-analysis

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.

Development and validation of a risk model for noninvasive detection of cancer in oral potentially malignant disorders using DNA image cytometry

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.

The evolution of robotics:research and application progress of dental implant robotic systems

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.

Fully automatic AI segmentation of oral surgery-related tissues based on cone beam computed tomography images

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.

Multivariate analysis of oral mucosal ulcers during orthodontic treatment

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.

The bacterial small RNAs: The new biomarkers of oral microbiotaassociated cancers and diseases

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.

Autophagy and circadian rhythms:interactions and clinical implications

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.

Expert consensus on endodontic therapy for patients withsystemic conditions

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.

Predictive value of serum alanine aminotransferase for fatty liver associated with metabolic dysfunction

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.

Transforming growth factor-β in stem cells and tissue homeostasis

TGF-β 1–3 are unique multi-functional growth factors that are only expressed in mammals, and mainly secreted and stored as a latent complex in the extracellular matrix(ECM). The biological functions of TGF-β in adults can only be delivered after ligand activation, mostly in response to environmental perturbations. Although involved in multiple biological and pathological processes of the human body, the exact roles of TGF-β in maintaining stem cells and tissue homeostasis have not been well-documented until recent advances, which delineate their functions in a given context. Our recent findings, along with data reported by others, have clearly shown that temporal and spatial activation of TGF-β is involved in the recruitment of stem/progenitor cell participation in tissue regeneration/remodeling process, whereas sustained abnormalities in TGF-β ligand activation, regardless of genetic or environmental origin, will inevitably disrupt the normal physiology and lead to pathobiology of major diseases. Modulation of TGF-β signaling with different approaches has proven effective pre-clinically in the treatment of multiple pathologies such as sclerosis/fibrosis, tumor metastasis, osteoarthritis, and immune disorders. Thus, further elucidation of the mechanisms by which TGF-β is activated in different tissues/organs and how targeted cells respond in a context-dependent way can likely be translated with clinical benefits in the management of a broad range of diseases with the involvement of TGF-β.

Oral health status in Sichuan Province: findings from the oral health survey of Sichuan, 2015–2016

To investigate oral health status in the residents of Sichuan Province, southwest China, a cross-sectional study was performed using the latest Oral Health Survey Basic Methods recommended by the World Health Organization. A multistage stratified random cluster-sampling method was used to enroll participants from the following three groups： children aged 3-5 years, adolescents aged 12 years, and people aged 65-74 years. In these three groups, the mean numbers of teeth that were affected by caries were 3.28, 0.86 and 5.13, respectively, resulting in a prevalence of 63.47%, 37.20% and 83.20%, respectively. Relative to the high rate of decayed teeth, the prevalence of fillings was very low in all age groups （0.97%, 7.24% and 5.43%, respectively）, In the 12-year-old adolescent group, only 3.61% had good pit and fissure sealing. In addition, the rate of dental fluorosis was 24.80%, and the Community Fluorosis Index value was 0.39. In the elder group, the community periodontal index was 2.92. The prevalence in the elderly of having lost at least one tooth was 75.54%. Additionally, 4.44% of these participants were edentulous. The incidence of dental prosthesis was 51.75%, the proportion with a removable partial denture, a fixed denture, full dentures, dental implants and an informal fixed bridge was 21.59%, 11.45%, 4.64%, 0 and 16.67%, respectively. In this study, 8.2% of the elderly participants were affected by different types of oral mucosal lesions. Among such lesions, recurrent aphthous ulcers were most prevalent （2.69%） and oral lichen planuses were second （1.6%）. The conclusion presented in this survey is that oral diseases, especially dental caries and periodontal disease, are frequent and common in Sichuan province, China. Moreover, the treatment rate is very low, and primary prevention and treatment options are therefore urgently needed in this population.

Aberrant activation of latent transforming growth factor-β initiates the onset of temporomandibular joint osteoarthritis

There is currently no effective medical treatment for temporomandibular joint osteoarthritis(TMJ-OA) due to a limited understanding of its pathogenesis. This study was undertaken to investigate the key role of transforming growth factor-β(TGF-β)signalling in the cartilage and subchondral bone of the TMJ using a temporomandibular joint disorder(TMD) rat model, an ageing mouse model and a Camurati–Engelmann disease(CED) mouse model. In the three animal models, the subchondral bone phenotypes in the mandibular condyles were evaluated by μCT, and changes in TMJ condyles were examined by TRAP staining and immunohistochemical analysis of Osterix and p-Smad2/3. Condyle degradation was confirmed by Safranin O staining, the Mankin and OARSI scoring systems and type X collagen(Col X), p-Smad2/3 a and Osterix immunohistochemical analyses. We found apparent histological phenotypes of TMJ-OA in the TMD, ageing and CED animal models, with abnormal activation of TGF-βsignalling in the condylar cartilage and subchondral bone. Moreover, inhibition of TGF-β receptor I attenuated TMJ-OA progression in the TMD models. Therefore, aberrant activation of TGF-β signalling could be a key player in TMJ-OA development.

Recent advances in cell sheet technology for bone and cartilage regeneration: from preparation to application

Bone defects caused by trauma,tumour resection,infection and congenital deformities,together with articular cartilage defects and cartilage–subchondral bone complex defects caused by trauma and degenerative diseases,remain great challenges for clinicians.Novel strategies utilising cell sheet technology to enhance bone and cartilage regeneration are being developed.The cell sheet technology has shown great clinical potential in regenerative medicine due to its effective preservation of cell–cell connections and extracellular matrix and its scaffold-free nature.This review will first introduce several widely used cell sheet preparation systems,including traditional approaches and recent improvements,as well as their advantages and shortcomings.Recent advances in utilising cell sheet technology to regenerate bone or cartilage defects and bone–cartilage complex defects will be reviewed.The key challenges and future research directions for the application of cell sheet technology in bone and cartilage regeneration will also be discussed.

Platelet-rich plasma for regeneration of neural feedback pathways around dental implants: a concise review and outlook on future possibilities

Along with the development of new materials, advanced medical imaging and surgical techniques, osseointegrated dental implants are considered a successful and constantly evolving treatment modality for the replacement of missing teeth in patients with complete or partial edentulism. The importance of restoring the peripheral neural feedback pathway and thus repairing the lack of periodontal rnechanoreceptors after tooth extraction has been highlighted in the literature. Nevertheless, regenerating the nerve fibers and reconstructing the neural feedback pathways around osseointegrated implants remain a challenge. Recent studies have provided evidence that platelet-rich plasma （PRP） therapy is a promising treatment for musculoskeletal injuries. Because of its high biological safety, convenience and usability, PRP therapy has gradually gained popularity in the clinical field Although much remains to be learned, the growth factors from PRP might play key roles in peripheral nerve repair mechanisms. This review presents known growth factors contributing to the biological efficacy of PRP and illustrates basic and （pre-）clinical evidence regarding the use of PRP and its relevant products in peripheral nerve regeneration. In addition, the potential of local application of PRP for structural and functional recovery of iniured peripheral nerves around dental implants is discussed.

Recent advances in smart stimuli-responsive biomaterials for bone therapeutics and regeneration

Bone defects combined with tumors, infections, or other bone diseases are challenging in clinical practice. Autologous and allogeneic grafts are two main traditional remedies, but they can cause a series of complications. To address this problem,researchers have constructed various implantable biomaterials. However, the original pathological microenvironment of bone defects, such as residual tumors, severe infection, or other bone diseases, could further affect bone regeneration. Thus, the rational design of versatile biomaterials with integrated bone therapy and regeneration functions is in great demand. Many strategies have been applied to fabricate smart stimuli-responsive materials for bone therapy and regeneration, with stimuli related to external physical triggers or endogenous disease microenvironments or involving multiple integrated strategies. Typical external physical triggers include light irradiation, electric and magnetic fields, ultrasound, and mechanical stimuli. These stimuli can transform the internal atomic packing arrangements of materials and affect cell fate, thus enhancing bone tissue therapy and regeneration. In addition to the external stimuli-responsive strategy, some specific pathological microenvironments, such as excess reactive oxygen species and mild acidity in tumors, specific p H reduction and enzymes secreted by bacteria in severe infection, and electronegative potential in bone defect sites, could be used as biochemical triggers to activate bone disease therapy and bone regeneration.Herein, we summarize and discuss the rational construction of versatile biomaterials with bone therapeutic and regenerative functions. The specific mechanisms, clinical applications, and existing limitations of the newly designed biomaterials are also clarified.