Oral epithelial dysplasia detection and grading in oral leukoplakia using deep learning.

BACKGROUND: The grading of oral epithelial dysplasia is often time-consuming for oral pathologists and the results are poorly reproducible between observers. In this study, we aimed to establish an objective, accurate and useful detection and grading system for oral epithelial dysplasia in the whole-slides of oral leukoplakia. METHODS: Four convolutional neural networks were compared using the image patches from 56 whole-slide of oral leukoplakia labeled by pathologists as the gold standard. Sequentially, feature detection models were trained, validated and tested with 1,000 image patches using the optimal network. Lastly, a comprehensive system named E-MOD-plus was established by combining feature detection models and a multiclass logistic model. RESULTS: EfficientNet-B0 was selected as the optimal network to build feature detection models. In the internal dataset of whole-slide images, the prediction accuracy of E-MOD-plus was 81.3% (95% confidence interval: 71.4-90.5%) and the area under the receiver operating characteristic curve was 0.793 (95% confidence interval: 0.650 to 0.925); in the external dataset of 229 tissue microarray images, the prediction accuracy was 86.5% (95% confidence interval: 82.4-90.0%) and the area under the receiver operating characteristic curve was 0.669 (95% confidence interval: 0.496 to 0.843). CONCLUSIONS: E-MOD-plus was objective and accurate in the detection of pathological features as well as the grading of oral epithelial dysplasia, and had potential to assist pathologists in clinical practice.

Mass cytometry and transcriptomic profiling reveal PD1 blockade induced alterations in oral carcinogenesis.

Oral squamous cell carcinoma is the predominant subtype of head and neck squamous cell carcinoma, characterized by a challenging prognosis. In this study, we established a murine model of oral carcinogenesis using 4-nitroquinoline-1-oxide (4-NQO) induction to investigate the impact of immunotherapy on microenvironmental alterations. Mice in the precancerous condition were randomly divided into two groups: one receiving programmed death-1 (PD1) monoclonal antibody treatment and the other, control immunoglobulin G. Our observations showed that while PD1 blockade effectively delayed the progression of carcinogenesis, it did not completely impede or reverse it. To unravel the underlying reasons for the limited effectiveness of PD1 blockade, we collected tongue lesions and applied mass cytometry (CyTOF) and RNA sequencing (RNA-seq) to characterize the microenvironment. CyTOF analysis revealed an increased macrophage subset (expressing high levels of IFNγ and iNOS) alongside a diminished Th1-like subset (exhibiting low expression of TCF7) and three myeloid-derived suppressor cell subsets (displaying low expression of MHC Class II or IFNγ) following anti-PD1 treatment. Notably, we observed an increased presence of cancer-associated fibroblasts (CAFs) expressing collagen-related genes after PD1 blockade. Furthermore, we found a negative correlation between the infiltration levels of CAFs and CD8+ T cells. These findings were validated in murine tongue tissue slides, and publicly available multi-omics datasets. Our results suggest that CAFs may impair the therapeutic efficacy of PD1 blockade in oral carcinogenesis by the remodeling of the extracellular matrix.

Association between periodontitis and mortality of patients with cardiovascular diseases: A cohort study based on NHANES.

BACKGROUND: The association between periodontitis and cardiovascular disease (CVD) has been widely explored, but little is known about the effect of periodontitis on the mortality of CVD patients. This study aims to clarify the effect of periodontitis on all-cause and cause-specific mortality of CVD patients. METHODS: We included 2,135 individuals with CVD from the National Health and Nutrition Examination Survey. Mortality data were ascertained by linkage to National Death Index records through 31 December 2019. We used Cox proportional hazards models for all-cause mortality and competing risk models for CVD and cancer mortality to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Further covariate adjustments, stratification analyses, and a variety of sensitivity analyses were conducted to test the reliability and robustness of the results. RESULTS: The all-cause mortality in CVD patients with moderate/severe periodontitis was significantly higher than in those with no/mild periodontitis (HR: 1.25; 95% CI: 1.02-1.52; P = 0.03). The all-cause mortality in participants with severe clinical attachment loss was significantly higher (HR: 1.07; 95% CI: 1.01-1.14; P = 0.01). However, no discrepancy in CVD or cancer mortality was observed between CVD patients with different periodontal status. CONCLUSIONS: Our findings from a longitudinal study with a large sample indicated significant but slightly higher all-cause mortality in CVD patients with moderate/severe periodontitis than in those with no/mild periodontitis.

A multi-center cross-sectional study of 1495 Chinese oral lichen planus patients.

OBJECTIVE: To explore the clinical epidemiological characteristics of oral lichen planus (OLP) and risk factors for erosive/ulcerative OLP. MATERIALS AND METHODS: Patients diagnosed with OLP from 11 different hospitals were included in the study. Descriptive statistical methods were used to explore the clinical epidemiological characteristics and logistic regression, sensitivity analysis, and subgroup analysis were utilized to explore the risk factors for erosive/ulcerative OLP. RESULTS: The average age of patients was 49.2 ± 13.3 years, and 61.4% of the patients were women. The ratios of patients with reticular, hyperemic/erythematous, and erosive/ulcerative lesions were 47.9%, 27.8%, and 24.2%, respectively. Analysis of risk factors for erosive/ulcerative OLP identified the following variables: age, course of disease of 12 months or more, II°-III° dental calculus, hypertension, diabetes, and heart disease, as well as regions of habitation. Subgroup analysis showed significant differences in risk factors for erosive/ulcerative OLP in patients with and without risk behaviors. CONCLUSION: The clinical epidemiological characteristics of patients with OLP in the Chinese population in this study are basically consistent with existing reports in developed countries. And we identified clinical characteristics associated with erosive/ulcerative OLP through clinical epidemiological analysis.

Hydroxychloroquine is effective in oral lichen planus: A multicenter, randomized, controlled trial.

OBJECTIVES: This study was aimed to evaluate the safety and benefit of short-term application of hydroxychloroquine in the management of atrophic/erosive/ulcerative oral lichen planus (OLP). METHODS: This multicenter, randomized, controlled, evaluator-blinded, prospective clinical trial was performed from October 1, 2019, to September 1, 2022. A total of 99 patients were randomized to receive systemic use of hydroxychloroquine (n = 50), or topical use of 0.05% dexamethasone (n = 49) for 4 weeks. The response to both treatment modalities was evaluated according to reticulation, hyperemic, and ulceration (RHU) score and visual analog scale (VAS) score. RESULTS: After 4 weeks of medication, both groups showed substantial reduction in RHU and VAS score (p < 0.05). In hydroxychloroquine group, the average of RHU score was reduced from 10.60 to 7.68 (dropped 27.49%), and the average of VAS score was reduced from 3.74 to 2.47 (dropped 34.09%). There were no differences between the two groups in reduction of RHU score and VAS score (p > 0.05). Single factor analysis found hyperemic area (p = 0.019) and erosive/ulcerative area (p = 0.024) had impacts on drug efficacy of hydroxychloroquine, and logistic regression revealed that no factors (p > 0.05) influenced its efficacy. CONCLUSION: These findings indicate hydroxychloroquine is a safe and effective agent in treating atrophic/erosive/ulcerative OLP.

Association between human herpes simplex virus and periodontitis: results from the continuous National Health and Nutrition Examination Survey 2009-2014.

BACKGROUND: Periodontitis is a common chronic oral disease which seriously affects people's quality of life. Although human herpes simplex virus (HSV) is also found in periodontal lesions, the association between HSV infection and periodontitis is unclear. METHODS: The National Health and Nutrition Examination Survey (NHANES) data for 2009-2010, 2011-2012 and 2013-2014 was combined, and the association between HSV infection and periodontitis in the general population and particular subgroups was investigated through weighted multi-logistic analyses. RESULTS: There were 4,733 participants aged 30-50 years old with clinically assessed periodontitis concurrent with HSV infection. In general analysis, after adjusted for covariates, both HSV-1 (OR = 1.09, P < 0.001) and HSV-2 (OR = 1.06, P = 0.030) infection was significantly associated with periodontitis. In subgroup analyses, compared with patients without HSV infection, patients with HSV-1( +) & HSV-2( +) and HSV-1( +) & HSV-2(-) infection showed higher risk of periodontitis in all subgroups (OR = 1.15, OR = 1.09, P < 0.001), while patients with HSV-1(-) & HSV-2( +) infection showed higher risk of and periodontitis only in the subgroup of people aged 40-50 years (OR = 1.10, P = 0.032) and the Mexican-American subgroup (OR = 1.35, P = 0.042). When only severe periodontitis is considered, HSV infection was associated with periodontitis, no matter the patient was infected with either of the virus or both. CONCLUSIONS: HSV-1 infection was significantly associated with periodontitis and severe periodontitis, while HSV-2 infection was associated with severe periodontitis, and periodontitis in 40-50-year-olds and Mexican-Americans.

Angelicin inhibits cell growth and promotes apoptosis in oral squamous cell carcinoma by negatively regulating DUSP6/cMYC signaling pathway.

Angelicin has been reported to have antitumor effects on many types of cancer. However, few studies on angelicin in oral squamous cell carcinoma (OSCC) have been performed. We performed cell cycle and apoptosis analyses to assess the effect of angelicin on OSCC cells. We conducted RNA-seq studies to reveal differentially expressed genes (DEGs). Dual-specificity phosphatase 6 (DUSP6) and c-MYC were strongly down-regulated differential genes. Silencing RNA (siRNA) was used to knockdown DUSP6. The mouse xenograft model was used to mimic OSCC. Angelicin inhibited OSCC in vitro. We found that DUSP6 interacted with c-MYC. DUSP6 knockdown group and DUSP6 knockdown + angelicin group had similar effects of OSCC cells. Angelicin could reduce tumor formation, DUSP6, and c-MYC expression in vivo. Compared with paclitaxel, the tumor inhibition effect of the two drugs was similar. However, angelicin did not cause weight loss and had lower toxicity. In sum, Angelicin has antitumor effects on OSCC in vitro and vivo by negatively regulating the DUSP6 mediated c-MYC signaling pathway.

Photodynamic therapy in focal epithelial hyperplasia.

Focal epithelial hyperplasia (FEH) is an uncommon benign disorder affecting the oral mucosa. It is primarily associated with human papillomavirus (HPV) infection and presents as multiple white or pink soft papules or nodules. Typically, FEH is asymptomatic. Conventional treatment approaches for FEH include topical medication, surgical excision, CO2 laser ablation, cryotherapy, etc., but their efficacy varies. Photodynamic therapy (PDT) is a non-invasive and selective photochemotherapy method widely utilized in clinical practice. By employing specific light wavelengths to activate photosensitizers and induce the generation of reactive oxygen, PDT exerts cytotoxic effects. However, the application of PDT in treating FEH has not been previously documented. In this study, we present a case demonstrating the complete remission of FEH lesions using PDT, with no recurrence observed over a period of 9 months. This compelling outcome suggests that PDT may be a preferred treatment modality for FEH.

CD8+ tissue-resident memory T cells induce oral lichen planus erosion via cytokine network.

CD8+ tissue-resident memory T (CD8+ Trm) cells play key roles in many immune-inflammation-related diseases. However, their characteristics in the pathological process of oral lichen planus (OLP) remains unclear. Therefore, we investigated the function of CD8+ Trm cells in the process of OLP. By using single-cell RNA sequencing profiling and spatial transcriptomics, we revealed that CD8+ Trm cells were predominantly located in the lamina propria adjacent to the basement membrane and were significantly increased in patients with erosive oral lichen planus (EOLP) compared to those with non-erosive oral lichen planus (NEOLP). Furthermore, these cells displayed enhanced cytokine production, including IFN-γ (Interferon-gamma, a pro-inflammatory signaling molecule), TNF-α (Tumor Necrosis Factor-alpha, a cytokine regulating inflammation), and IL-17 (Interleukin-17, a cytokine involved in immune response modulation), in patients with EOLP. And our clinical cohort of 1-year follow-up was also supported the above results in RNA level and protein level. In conclusion, our study provided a novel molecular mechanism for triggering OLP erosion by CD8+ Trm cells to secrete multiple cytokines, and new insight into the pathological development of OLP.

MRTF-A/SRF signaling suppresses invasion of oral squamous cell carcinoma.

BACKGROUND: Serum response factor (SRF) and myocardial-associated transcription factor-A (MRTF-A) had different regulatory effects on the tumorigenesis and development in different cancers. However, the role of MRTF-A/SRF in oral squamous cell carcinoma (OSCC) remains to be determined. METHODS: CCK-8 assay, cell scratch experiment, and transwell invasion assay were conducted to investigate the effects of MRTF-A/SRF on biological behavior of OSCC cells. The expression pattern and prognostic value of MRTF-A/SRF in OSCC were analyzed based on cBioPortal website and TCGA database. Protein-protein interaction network was visualized to identify protein functions. Go and KEGG pathway analyses were performed to investigate related pathways. The effect of MRTF-A/SRF on epithelial-mesenchymal transformation (EMT) of OSCC cells was explored by western blot assay. RESULTS: Overexpression of MRTF-A/SRF inhibited the proliferation, migration, and invasion of OSCC cells in vitro. High expression of SRF was related to better prognosis of OSCC patients on hard palate, alveolar ridge, and oral tongue. Besides, overexpression of MRTF-A/SRF inhibited the EMT of OSCC cells. CONCLUSION: SRF was closely related to the prognosis of OSCC. High expression of SRF and its co-activator MRTF-A inhibited proliferation, migration, and invasion of OSCC cells in vitro, possibly via EMT suppression.

circFANCA accelerates the malignant process of OSCC by modulating miR-34a/PA28γ signaling.

OBJECTIVES: To investigate the upstream regulatory molecules of proteasomal activator 28γ (PA28γ), and explore its specific regulatory mechanism and potential clinical significance in OSCC. MATERIALS AND METHODS: qPCR was used to examine miR-34a, circFANCA and PSME3 expression. Western blotting was adopted to detect PA28γ expression. Transwell experiments were conducted to evaluate OSCC cell migration and invasion ability. FISH was used to evaluate the subcellular localization of circFANCA and miR-34a, and RNA pull-down verified the interaction between them. The expression of circFANCA and miR-34a in clinical cohorts was assessed by ISH, and the results were subjected to survival analysis using Kaplan-Meier analysis. RESULTS: Here, we proved that miR-34a expression is lower in highly aggressive OSCC tissues and cell lines. Notably, miR-34a can downregulate PA28γ expression and inhibit OSCC invasion and migration. Next, we confirmed that circFANCA promoted OSCC cell metastatic ability by sponging miR-34a. Importantly, interfering with miR-34a rescued the malignant progression of OSCC induced by silencing circFANCA. Finally, clinical data showed lower miR-34a expression and higher circFANCA expression were associated with poor prognosis in OSCC patients. CONCLUSION: The circFANCA/miR-34a/PA28γ axis facilitates the metastasis of OSCC, and circFANCA and miR-34a have potential to serve as prognostic markers for OSCC patients.

First Report of Fusarium solani associated with Twig Canker of English Walnut (Juglans regia L.) in Xinjiang, China.

English walnut (Juglans regia L.) is a perennial deciduous fruit tree, and an economically important hardwood tree species cultivated worldwide. As one of the important economic crops, English walnut is also widely cultivated in Xinjiang. In September 2019, twig canker symptoms were observed on English walnut in several orchards, with approximately 15% to 40% disease incidence in southern Xinjiang region (79º95'E, 40º37'N). The branch lesions were long oval, concave, and black to brown. Leaves of the affected branches turned yellow and the branches eventually died. Infected twigs were collected from an infected tree in an orchard. Symptomatic tissue from the margins of cankers was surface disinfested with 75% ethanol for 60 s, rinsed 3 times with sterile water, and then incubated on potato dextrose agar medium (PDA) at 25 ℃ under a 12-hr photoperiod in Light incubator for 7 days. Seven fungal isolates showing similar morphology were obtained from the symptomatic tissue. All the fungal cultures had a pink-white color with loose, cottony mycelium, and the underside of the colonies were light brown. Macroconidia were slightly curved, with one to six septa, both ends were slightly sharp, and they measured 22.8 to 38.5 × 3.5 to 6.7 µm (27.4 ± 0.6 × 4.2 ± 0.3 µm, n=50). Microconidia were oval, hyaline, zero to one septa, measuring 4.5 to 9.6 × 1.8 to 2.3 µm (6.8 ± 0.3 × 2.1 ± 0.1 µm, n=50). According to the morphological characteristics, the seven isolates were identified as a member of the Fusarium solani species complex (Summerell et al. 2003). Genomic DNA was extracted from the representative isolate HSANTUAN2019-1, and the internal transcribed spacer (ITS) region, the translation elongation factor 1-alpha (TEF) were amplified with the primer pairs ITS1/ITS4 (White et al. 1990) and EF1-F/EF2-R (O' Donnell et al. 2010), respectively. The sequences submitted to GenBank (accession nos. OP271472 for ITS, OP293104 for TEF) showed high similarity with the reference sequences of F. solani (ITS, OL691083 [100%]; TEF, HE647960 [99.86%]). Pathogenicity of the seven isolates were assessed on 1-year-old branches of English walnut in the field. Healthy branches (40) were wounded with a sterilized hole punch, and then inoculated with isodiametric mycelial PDA plugs (5 branches per fungal isolate). Five branches were inoculated with sterile PDA plugs as a negative control. The inoculations were performed three times. All treatments were wrapped with fresh film for 3 days. Dark brown necrotic lesions were observed on all inoculated branches 22 days post-inoculation. The controls had no symptoms. The pathogen was reisolated from all the inoculated branches, fulfilling Koch's postulates. To our knowledge, this is the first report of F. solani causing twig canker on English walnut in Xinjiang, China. Twig canker disease often cause a large number of branches to dry out and die. If the disease control and prevention is neglected, the productivity of the English walnut will be seriously affected in the cultivation area. Our finding will provide valuable information for prevention and management of twig canker on English walnut.

World Workshop on Oral Medicine VIII: Development of a core outcome set for oral lichen planus: a consensus study.

OBJECTIVE: A core outcome set (COS) is the minimum agreed-on data set required to be measured in interventional trials. To date, there is no COS for oral lichen planus (OLP). This study describes the final consensus project that brought together the results of the previous stages of the project to develop the COS for OLP. STUDY DESIGN: The consensus process followed the Core Outcome Measures in Effectiveness Trials guidelines and involved the agreement of relevant stakeholders, including patients with OLP. Delphi-style clicker sessions were conducted at the World Workshop on Oral Medicine VIII and the 2022 American Academy of Oral Medicine Annual Conference. Attendees were asked to rate the importance of 15 outcome domains previously identified from a systematic review of interventional studies of OLP and a qualitative study of OLP patients. In a subsequent step, a group of OLP patients rated the domains. A further round of interactive consensus led to the final COS. RESULTS: The consensus processes led to a COS of 11 outcome domains to be measured in future trials on OLP. CONCLUSION: The COS developed by consensus will help reduce the heterogeneity of outcomes measured in interventional trials. This will allow future pooling of outcomes and data for meta-analyses. This project showed the effectiveness of a methodology that could be used for future COS development.

World Workshop on Oral Medicine VIII: Development of a core outcome set for oral lichen planus: a systematic review of outcome domains.

OBJECTIVE: There is a lack of consensus regarding clinician- and patient-reported oral lichen planus (OLP) outcomes. The World Workshop on Oral Medicine Outcomes Initiative for the Direction of Research (WONDER) Project aims to develop a core outcome set (COS) for OLP, which would inform the design of clinical trials and, importantly, facilitate meta-analysis, leading to the establishment of more robust evidence for the management of this condition and hence improved patient care. STUDY DESIGN: Ovid MEDLINE, Embase, CINAHL, CENTRAL, and Clinicaltrials.gov were searched for interventional studies (randomized controlled trials, controlled clinical trials, and case series including ≥5 participants) on OLP and oral lichenoid reactions published between January 2001 and March 2022 without language restriction. All reported primary and secondary outcomes were extracted. RESULTS: The searches yielded 9,135 records, and 291 studies were included after applying the inclusion criteria. A total of 422 outcomes were identified. These were then grouped based on semantic similarity, condensing the list to 69 outcomes. The most frequently measured outcomes were pain (51.9%), clinical grading of the lesions (29.6%), lesion size/extension/area (27.5%), and adverse events (17.5%). CONCLUSION: As a first step in developing a COS for OLP, we summarized the outcomes that have been used in interventional studies over the past 2 decades, which are numerous and heterogeneous.

Single-cell immune profiling reveals immune responses in oral lichen planus.

Introduction: Oral lichen planus (OLP) is a common chronic inflammatory disorder of the oral mucosa with an unclear etiology. Several types of immune cells are involved in the pathogenesis of OLP. Methods: We used single-cell RNA sequencing and immune repertoire sequencing to characterize the mucosal immune microenvironment of OLP. The presence of tissue-resident memory CD8+ T cells are validated by multiplex immunofluorescence. Results: We generated a transcriptome atlas from four OLP biopsy samples and their paired peripheral blood mononuclear cells (PBMCs), and compared them with two healthy tissues and three healthy PBMCs samples. Our analysis revealed activated tissue-resident memory CD8+ T cells in OLP tissues. T cell receptor repertoires displayed apperant clonal expansion and preferrential gene pairing in OLP patients. Additionally, obvious BCR clonal expansion was observed in OLP lesions. Plasmacytoid dendritic cells, a subtype that can promote dendritic cell maturation and enhance lymphocyte cytotoxicity, were identified in OLP. Conventional dendritic cells and macrophages are also found to exhibit pro-inflammatory activity in OLP. Cell-cell communication analysis reveals that fibroblasts might promote the recruitment and extravasation of immune cells into connective tissue. Discussion: Our study provides insights into the immune ecosystem of OLP, serving as a valuable resource for precision diagnosis and therapy of OLP.

World Workshop on Oral Medicine VIII: Development of a core outcome set for oral lichen planus: the patient perspective.

OBJECTIVE: This study aimed to explore the lived experience of patients with oral lichen planus (OLP) and investigate what treatment-related outcomes are the most important to them and should be included in a core outcome set (COS) for OLP. STUDY DESIGN: A qualitative study involving focus group work with 10 participants was conducted. Interviews with each focus group were held twice: session 1 explored the lived experience of patients with OLP, and session 2 allowed patients to review a summary of the outcome domains used in the OLP literature to date. The discussions were recorded, transcribed verbatim, and analyzed using framework analysis. RESULTS: In session 1, 4 themes and 8 sub-themes emerged from the data analysis. An additional outcome, 'knowledge of family and friends,' was suggested in session 2. CONCLUSIONS: We have gained valuable insight into the lived experience of patients with OLP via this qualitative study. To our knowledge, this study is the first to explore the patient perspective on what should be measured in clinical trials on OLP, highlighting an important additional suggested outcome. This additional outcome will be voted upon in a consensus process to determine a minimum COS for OLP.

The research status and progress of core outcome set in oral health.

The core outcome set (COS) refers to the minimum set of outcomes that should be reported by all clinical trials in a particular health field. The use of COS in clinical studies can reduce the heterogeneity caused by using different outcomes across different clinical studies, facilitate the systematic review of different clinical studies on the same topic, reduce selective reporting bias, and increase the utility of clinical studies. The importance of COS in oral health has recently been recognized. This review summarizes the history, necessity, and key methodological points of COS development, with emphasis on the research status and existing problems in COS development, in the field of oral health.

Injectable catechin-based supramolecular hydrogel for highly efficient application in HPV-associated OSCC.

Catechins are a group of natural polyphenols extracted from green tea. Notably, they have been proven to have excellent anti-HPV and anti-tumour properties and to be effective against some HPV-related diseases, showing great potential in the treatment of HPV-associated oral squamous cell carcinoma (HPV+ OSCC). However, the poor bioavailability, short half-lives, and stability issues of catechins hamper their clinical application. To overcome these shortcomings of catechins, we innovatively synthesised an injectable supramolecular hydrogel, namely catechin-phenylenebisboronic acid-isoguanosine (CPBisoG), with catechin (one of the simplest catechins) and isoguanosine (isoG), another natural product with self-assembly ability, via dynamic phenylborate diester bonds. The biodegradation and sustained-release time of the CPBisoG hydrogel in mice lasted up to 72 h. This supramolecular hydrogel not only functioned as a good local drug delivery platform with good stability, injectability, self-healing properties, biocompatibility, biodegradability, but also exhibited therapeutic effects toward HPV+ OSCC in vitro and in vivo. And interestingly, it also showed selective inhibition against HPV+ OSCC cells. In all, these results demonstrate that this catechin-based hydrogel could sustainedly and highly effectively treat HPV+ OSCC topically, which could also provide a promising strategy for the management of other HPV-associated diseases in the future.

Single-cell transcriptomics dissects premalignant progression in proliferative verrucous leukoplakia.

OBJECTIVE: Proliferative verrucous leukoplakia (PVL) is characterized by a spectrum of clinicopathological features and a high risk of malignant transformation. In this study, we aimed to delineate the dynamic changes in molecular signature during PVL progression and identify the potential cell subtypes that play a key role in the premalignant evolution of PVL. METHODS: We performed single-cell RNA sequencing on three biopsy samples from a large PVL lesion. These samples exhibited a histopathological continuum of PVL progression. RESULTS: By analyzing the transcriptome profiles of 27,611 cells from these samples, we identified ten major cell lineages and revealed that cellular remodeling occurred during the progression of PVL lesions, including epithelial, stromal, and immune cells. Epithelial cells are shifted to tumorigenic states and secretory patterns at the premalignant stage. Immune cells showed growing immunosuppressive phenotypes during PVL progression. Remarkably, two novel cell subtypes INSR+ endothelial cells and ASPN+ fibroblasts, were discovered and may play vital roles in microenvironment remodeling, such as angiogenesis and stromal fibrosis, which are closely involved in malignant transformation. CONCLUSION: Our work is the first to depict the cellular landscape of PVL and speculate that disease progression may be driven by functional remodeling of multiple cell subtypes.

Photodynamic therapy-a promising treatment of oral mucosal infections.

The treatment of oral mucosal infections is increasingly challenging owing to antibiotic resistance. Therefore, alternative antimicrobial strategies are urgently required. Photodynamic therapy (PDT) has attracted attention for the treatment of oral mucosal infections because of its ability to effectively inactivate drug-resistant bacteria, completely heal clinical infectious lesions and usually offers only mild adverse reactions. This review briefly summarizes relevant scientific data and published papers and discusses the potential mechanism and application of PDT in the treatment of oral mucosal infections.