Expression and significance of p53 and mdm2 in patients with leukoplakia cancer

Objective:To study the relationship of the expressions of p53 and mdm2 in leukoplakia cancer.Methods:RT-PCR was used to detect the mRNA of p53,mdm2 in patients with leukoplakia cancer.The frequencies of p53,mdm2 in peripheral blood were detected by flow cytometric analysis.Results:The expression of p53mRNA in normal oral mucosa,simple oral leukoplakia,no-simple oral leukoplakia and leukoplakia cancer were 7.7%,27.3%,33.3%,56.8%,respectively.The frequencies of p53 in normal oral mucosa,simple oral leukoplakia,no-simple oral leukoplakia and leukoplakia cancer were(0.3±0.1)%,(l.6±0.9)%,(1.9±1.1)%,(3.4±1.8)%.The expression of mdm2 mRNA in normal oral mucosa,simple oral leukoplakia,no-simple oral leukoplakia and leukoplakia cancer were 0.0%,6.8%,11.1%,37.8%,respectively.The frequencies of mdm2 in normal oral mucosa,simple oral leukoplakia,no-simple oral leukoplakia and leukoplakia cancer were(0.1±0.1)%,(0.8±0.6)%,(1.2±0.8)%,(1.2±0.8)%.There was a positively correlation between p53 mRNA and mdm2 mRNA.Conclusions:The positive rate of p53 and mdm2 cells in the peripheral blood increases in patients with leukoplakia cancer tissue and has positive correlation with the severity of leukoplakia cancer.

Photodynamic therapy of oral leukoplakia and orallichen planus using methylene blue:A pilot study

Premalignant lesions like oral lichen planus(OLP),oral leukoplakia(OL)has a fair probability of transforming into malignancy and they are perverse toward conventional therapies.Photody-namic therapy(PDT)has been considered as an alternative/complimentary therapeutic mo-dality for the management of premalignant lesions.In this study,methylene blue mediated photodynamic therapy(MB-PDT)was used as a possible alternative method for the treatment of OLP and OL.A total of 15 OLP lesions and 13 OL lesions were enrolled in the study.The patients were irradiated 1using metal halide lamp filtered at 630土10nm,with a light exposure dose of 120 J/cm^(2) per stting.For the OLP lesions,MB-PDT was performed once a week for four weeks and for the OL lesions,MB-PDT was performed twice a week for three weeks.Lesions were evaluated pre-and post-and at follow-u sessions by changes in sign and symptom scores,and size of lesions.We have observed a 53.3%of complete reduction in the treated OLP lesions and their decrease in size,sign and symptom score after treatment and at follow-up session was statistially signifcant.We have also observed complete response for one OL lesion of the 13 treated lesions.The result indicates that MB-PDT is an effective modality in management of OLP and OL.Among the two types of premalignancies treated with MB-PDT,OLP lesions responded much better than that of OL.

Upregulation of epidermal growth factor receptor 4 in oral leukoplakia

In the present study,we investigate the expression profile of the epidermal growth factor receptor family,which comprises EGFR/ ErbBl,HER2/ErbB2,HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia(LP).The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus(OLP) and normal oral mucosa(NOM) from 14 healthy donors by real-time polymerase chain reaction(PCR) and immunohistochemistry.Synchronous mRNA coexpression of ErbBl,ErbB2,ErbB3and ErbB4 was detected in LP lesions.Out of the receptors,only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM tissues.These were strongly expressed by epithelial keratinocytes in LP lesions,as shown by immunohistochemistry.Regarding the ligands,the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM tissues.Therefore,enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.

Low expression of angiotensinogen and dipeptidyl peptidase 1 in saliva of patients with proliferative verrucous leukoplakia

AIM To elucidate the profile of the salivary proteome.METHODS Unstimulated whole mouth saliva was collected from 30 volunteers [15 proliferative verrucous leukoplakia(PVL) patients and 15 controls] and proteins were submitted for mass spectrometry-based proteomics using the discovery approach,followed by analyses of variance and logistic regression tests.RESULTS A total of two hundred and eighty-three proteins were confidently identified in saliva.By combining two low abundance proteins from the PVL group,angiotensinogen(AGT) and dipeptidyl peptidase 1(DPP1),a model for group differentiation was built with a concordance index of 94.2%,identifying both proteins as potential etiologic biomarkers for PVL.CONCLUSION This study suggests that both AGT and DPP1 may be involved in developmental mechanisms of PVL.

Critical review of topical management of oral hairy leukoplakia

Oral hairy leukoplakia(OHL) is a disease associated with Epstein-Barr virus and human immunodeficiency virus infections. OHL is usually an asymptomatic lesion, but in some cases treatment is recommended to reestablish the normal characteristics of the tongue, to eliminate pathogenic microorganisms, to improve patient comfort and for cosmetic reasons. Proposed treatments for this condition include surgery, systemic antiviral treatment and topical management. Topical treatment is an inexpensive and safe therapy that is easy to apply, noninvasive, free of systemic adverse effects and effective over a long period of time. The aim of this study was to present a review of the literature for topical therapy for OHL. Gentian violet, retinoids, podophyllin, acyclovir and podophyllin associated with topical antiviral drugs were used to treat OHL. Reports with this focus are limited, and since 2010, no new studies have been published that discuss the efficacy of topical treatments for OHL. Podophyllin with acyclovircream was found to be effective, causing regression of lesions with no recurrences. Additional searches are necessary to provide clinical evidence of topical man agement effectiveness.

The use of traditional Chinese medicine internally and externally combined with auricular acupuncture point bloodletting in the treatment of vulvar leukoplakia

Vulvar leukoplakia refers to the chronic disease of degeneration and hypopigmentation of the skin and mucous membrane of the vulva with unbearable itching in women, seriously affecting the quality of life. The main treatment of western medicine for vulvar leukoplakia is the external use of glucocorticoids or estrogen, resulting to the high recurrence rate and side effects. Traditional Chinese medicine (TCM) has the characteristics of the overall concept and dialectical treatment with a variety of ways. Literature review in recent years found that the treatment of TCM decoction combined with external therapies, such as external fumigation, acupuncture and other treatments, or the combination of TCM decoction and external western medicine hormone ointment, can obtain good effects in vulvar leukoplakia. During the clinical practice, we found that the use of TCM internally and externally combined with auricular acupuncture point bloodletting was highly effective with unique advantages in the treatment of vulvar leukoplakia, providing the ideas guidance for clinicians.

C-Ha-ras Oncogene in Oral Leukoplakia Tissues

The amplification and the G-T mutation at codon 12 of the C-Ha-ras oncogene in oral leukoplakia tissues were analyzed by using polymerase chain reaction (PCR) and molecular biologic technique. The results showed that these tissues had no amplification of Ha-ras oncogene. Only one case harbored G-T mutation in 11 oral leukoplakias, but this mutation was absent in 10 normal oral mucosal tissues. The possible role and significance of C-Ha-ras oncogene in oral precancerous lesions were also discussed.

Proliferative verrucous leukoplakia may initially mimic lichenoid reactions

Proliferative verrucous leukoplakia is an intriguing disease, which occurs particularly in women aged greater than 60 years, is not associated with tobacco and alcohol, and has a high risk of recurrence and malignant transformation. Although it is well known that the typical presentation is characterized by multifocal and verrucous white lesions, there is no description that its initial clinical presentation may simulate a lichenoid reaction.

Oriented cellulose hydrogel:Directed tissue regeneration for reducing corneal leukoplakia and managing fungal corneal ulcers

Fungal corneal ulcer is one of the leading causes of corneal blindness in developing countries.Corneal scars such as leukoplakia are formed due to inflammation,oxidative stress and non-directed repair,which seriously affect the patients'subsequent visual and life quality.In this study,drawing inspiration from the oriented structure of collagen fibers within the corneal stroma,we first proposed the directional arrangement of CuTA-CMHT hydrogel system at micro and macro scales based on the 3D printing extrusion method combined with secondary patterning.It played an antifungal role and induced oriented repair in therapy of fungal corneal ulcer.The results showed that it effectively inhibited Candida albicans,Aspergillus Niger,Fusarium sapropelum,which mainly affects TNF,NF-kappa B,and HIF-1 signaling pathways,achieving effective antifungal functions.More importantly,the fibroblasts interacted with extracellular matrix(ECM)of corneal stroma through formation of focal adhesions,promoted the proliferation and directional migration of cells in vitro,induced the directional alignment of collagen fibers and corneal stromal orthogonally oriented repair in vivo.This process is mainly associated with MYLK,MYL9,and ITGA3 molecules.Furthermore,the downregulation the growth factors TGF-βand PDGF-βinhibits myofibroblast development and reduces scar-type ECM production,thereby reducing corneal leukoplakia.It also activates the PI3K-AKT signaling pathway,promoting corneal healing.In conclusion,the oriented CuTA-CMHT hydrogel system mimics the orthogonal arrangement of collagen fibers,inhibits inflammation,eliminates reactive oxygen species,and reduces corneal leukoplakia,which is of great significance in the treatment of fungal corneal ulcer and is expected to write a new chapter in corneal tissue engineering.

窄带成像技术与白光成像技术在支撑喉镜下声带白斑切除术中的应用效果比较

目的比较窄带成像(NBI)技术与传统的白光成像(WLE)技术在支撑喉镜下行声带白斑切除时确定手术安全边界的效果。方法选取2021年10月—2023年9月于东莞市莞城医院接受治疗的32例中重度声带白斑患者,采用随机数字表法分为试验组和对照组各16例。试验组采用NBI辅助的支撑喉镜声带白斑切除术,对照组采用传统的WLE技术辅助的支撑喉镜声带白斑切除术。比较两组患者在不同技术下行手术并进行首次切除后所切除组织边缘的病理学分析结果。结果两组手术均安全无事故完成,对照组术中组织切缘的冷冻病理样本阳性切缘发生率为18.75%(3/16),试验组术中组织切缘的冷冻病理样本阳性切缘发生率为6.25%(1/16),试验组阳性切缘发生率低于对照组,但差异无统计学意义(P>0.05);试验组术中冷冻病理与术后病理诊断符合率为93.75%,术中冷冻病理诊断敏感度为50.00%、阳性预测值为100%;对照组术中冷冻病理与术后病理诊断符合率为75.00%,术中冷冻病理诊断敏感度为42.86%、阳性预测值为100%。试验组术中冷冻病理与术后病理诊断符合率、术中冷冻病理诊断敏感度高于对照组,但差异无统计学意义(P>0.05)。结论与传统WLE技术相比,采用NBI辅助支撑喉镜声带白斑切除手术能更准确地确定术中安全边界。

Improvement in the risk assessment of oral leukoplakia through morphology-related copy number analysis

Oral leukoplakia is the most common type of oral potentially malignant disorders and considered a precursor lesion to oral squamous cell carcinoma.However,a predictor of oral leukoplakia prognosis has not yet been identified.We investigated whether copy number alteration patterns may effectively predict the prognostic outcomes of oral leukoplakia using routinely processed paraffin sections.Comparison of copy number alteration patterns between oral leukoplakia with hyperplasia(HOL,n=22)and dysplasia(DOL,n=21)showed that oral leukoplakia with dysplasia had a higher copy number alteration rate(86%)than oral leukoplakia with hyperplasia(46%).Oral leukoplakia with dysplasia exhibited a wider range of genomic variations across all chromosomes compared with oral leukoplakia with hyperplasia.We also examined a retrospective cohort of 477 patients with oral leukoplakia with hyperplasia with detailed follow-up information.The malignant transformation(MT,n=19)and leukoplakia recurrence(LR,n=253)groups had higher frequencies of aneuploidy events and copy number loss rate than the free of disease(FD,n=205)group.Together,our results revealed the association between the degree of copy number alterations and the histological grade of oral leukoplakia and demonstrated that copy number alteration may be effective for prognosis prediction in oral leukoplakia patients with hyperplasia.

Biomarkers of malignant transformation in oral leukoplakia:from bench to bedside

Oral leukoplakia is a common precursor lesion of oral squamous cell carcinoma,which indicates a high potential of malignancy.The malignant transformation of oral leukoplakia seriously affects patient survival and quality of life;however,it is difficult to identify oral leukoplakia patients who will develop carcinoma because no biomarker exists to predict malignant transformation for effective clinical management.As a major problem in the field of head and neck pathologies,it is imperative to identify biomarkers of malignant transformation in oral leukoplakia.In this review,we discuss the potential biomarkers of malignant transformation reported in the literature and explore the translational probabilities from bench to bedside.Although no single biomarker has yet been applied in the clinical setting,profiling for genomic instability might be a promising adjunct.

Importance of complementary data to histopathological image analysis of oral leukoplakia and carcinoma using deep neural networks

Background Oral cancer is one of the most common types of cancer in men causing mortality if not diagnosedearly.In recent years,computer-aided diagnosis(CAD)using artificial intelligence techniques,in particular,deepneural networks have been investigated and several approaches have been proposed to deal with the automateddetection of various pathologies using digital images.Recent studies indicate that the fusion of images with thepatient’s clinical information is important for the final clinical diagnosis.As such dataset does not yet exist fororal cancer,as far as the authors are aware,a new dataset was collected consisting of histopathological images,demographic and clinical data.This study evaluated the importance of complementary data to histopathologicalimage analysis of oral leukoplakia and carcinoma for CAD.Methods A new dataset(NDB-UFES)was collected from 2011 to 2021 consisting of histopathological imagesand information.The 237 samples were curated and analyzed by oral pathologists generating the gold standardfor classification.State-of-the-art image fusion architectures and complementary data(Concatenation,MutualAttention,MetaBlock and MetaNet)using the latest deep learning backbones were investigated for 4 distincttasks to identify oral squamous cell carcinoma,leukoplakia with dysplasia and leukoplakia without dysplasia.We evaluate them using balanced accuracy,precision,recall and area under the ROC curve metrics.Results Experimental results indicate that the best models present balanced accuracy of 83.24%using images,demographic and clinical information with MetaBlock fusion and ResNetV2 backbone.It represents an improvement in performance of 30.68%(19.54 pp)in the task to differentiate samples diagnosed with oral squamous cellcarcinoma and leukoplakia with or without dysplasia.Conclusion This study indicates that cured demographic and clinical data may positively influence the performance of artificial intelligence models in automated classification of oral cancer.

MORPHOMETRIC ANALYSIS OF SPINOUS CELL IN ORAL SUBMUCOUS FIBROSIS COMPARISON WITH NORMAL MUCOSA, LEUKOPLAKIA AND SQUAMOUS CELL CARCINOMA

The morphometric analysis of the spinous cell in 16 specimens of oral submucous fibrosis (OSF) was made by using interactive image analysis system (IBAS-II). 19 parameters of the size and shape were chosen, and compared with normal mucosa, leukoplakia, dysplasia and carcinoma. The results indicated that the cell dimensions (area, perimeter, all kinds of diameter) and nuclear cytoplasmic ratio in OSF were between normal mucosa and dysplasia as well as carcinoma. The former showed a progressive decrease (P<0.01), and the latter showed a progressive increase (P<0.01). The dimensions of the nuclei did not show considerable differences among the groups (P>0.05). A series of discriminant functions had been developed with stepwise discriminant analysis, the agreement ratio for OSF was 93.75%. The decrease of cell area and the increase of nuclear cytoplasmic ratio could reflect a malignant progress. The cell morphometric model could discriminate OSF well from other groups, suggesting that the change of the epith

计算机辅助下自体荧光图像定量结果与口腔白斑病上皮异常增生等级的相关性

目的·探究计算机辅助下自体荧光图像定量结果与口腔白斑病上皮异常增生等级的相关性。方法·纳入2016年4月—2024年1月于上海交通大学医学院附属第九人民医院口腔黏膜病科就诊的口腔白斑病患者357例。利用手持自体荧光仪器获取患者病损的自体荧光图像,将自体荧光图像转为灰度图像,获得量化指标。在Python中拟合有序多元Logistic回归模型,绘制累积概率图。将数据集划分训练集和测试集,生成决策树,调整不同的超参数,获得最佳的模型效果。计算准确度、精确度和F1分值。利用混淆矩阵对模型性能进行可视化呈现。结果·随着上皮异常增生程度的增加,相对色阶平均值呈现下降趋势。在上皮异常增生二分类中累积概率图不同类别曲线之间无重叠,在四分类中仅上皮重度异常增生与其他类别曲线有重叠,说明模型的区分能力较好。在二分类病理等级中,当训练集和测试集比例为4∶1、决策树最大深度为2时,准确度、精确度、F1分值可达到较高,分别为0.792、0.801和0.795。在四分类病理等级中,当训练集和测试集比例为9∶1、决策树最大深度为4时,准确度、精确度、F1分值可达到较高,分别为0.611、0.537和0.569。结论·口腔黏膜病专科医师可将计算机辅助下自体荧光图像定量结果作为参考依据,预测口腔白斑病患者上皮异常增生程度,监控患者癌变风险。

喉白斑的窄带成像内镜下诊断与病理分析

目的 探讨通过窄带成像(narrow band imaging,NBI)电子喉镜下观察喉黏膜上皮内的毛细血管袢形态,能否指导喉白斑患者治疗方法的选择。方法 选取2019年6月~2021年9月临床诊断为喉白斑的68例患者为研究对象,根据NBI电子喉镜的诊断结果,将患者分为两组:良性病变组(52/68)和恶性病变组(16/68)。比较NBI喉镜诊断与病理检查结果的一致性。结果良性病变组中病理确诊为鳞状上皮增生伴角化35例(67.31%),轻度不典型增生9例(17.31%),中度不典型增生3例(5.77%),原位癌5例(9.62%),恶性病变组中病理确诊为中度不典型增生2例(12.50%),重度不典型增生1例(6.25%),原位癌9例(56.25%),浸润癌4例(25.00%)。采用Kappa一致性检验法,k=0.687,P<0.001,说明NBI电子喉镜诊断结果和病理检查结果存在一致性。结论 NBI电子喉镜能很好的分辨喉白斑的性质,对喉白斑治疗方法的选择和随访观察喉白斑的进展有较高的指导意义。

基于皮肤镜的外阴白斑无创诊断与疗效评估

外阴白斑是妇科常见病,临床上可以通过患者症状、体征对该病作出临床诊断,但外阴活组织病理检查(外阴活检)是诊断的金标准,也是疗效评价的客观指标。鉴于外阴活检的有创性和女性外阴的特殊性,无论是基于诊断目的的初次活检还是基于疗效评估目的的再次活检在临床应用的阻力都非常大,同时有违人道精神和微无创的医学发展理念。有鉴于此,团队结合近三十年使用自制中药膏无创治疗该病的经历、经验,率先提出使用皮肤镜对该病进行无创诊断和疗效评估的理念并进行了系列开创性研究,取得相应研究结果。本文即根据外阴白斑研究现状和团队的研究结果撰写的一篇述评,希望借此引起妇产科学界对皮肤镜用于外阴白斑无创诊断与疗效评估的重视,逐渐提高其研究、应用的普及率、准确性,服务临床、造福患者。

内外合治法治疗老年性外阴白斑验案一则

黄艳辉教授认为外阴白斑多由内外因合而致病,内因多责于肝、脾、肾三脏功能失调,肝肾阴血亏虚,脾虚气血生化乏源,阴户失养,血燥生风而痒;外因责于自然界中风、热、燥、湿、虫等外邪侵袭。黄艳辉教授通过总结前人治疗外阴白斑的经验及自身多年临床经验,认为对外阴白斑的治疗应采取内外同治法,内治重在滋补肝肾,佐以健脾利湿、活血补血等;外治重在局部以清热祛湿止痒。

NBI内镜对声带白斑病变性质的评估价值

目的探讨窄带成像(narrow band imaging,NBI)内镜对声带白斑病变性质的评估价值。方法回顾性分析95例(153侧)声带白斑患者(58例双侧,37例单侧)的临床资料,所有患者在显微喉镜手术前均进行电子喉镜检查,先用普通白光检查声带病变,再用NBI模式检查。根据NBI内镜下白斑及上皮内乳头样毛细血管袢(intraepithelial papillary capillary loop,IPCL)的形态特征,分为低危组(I型、II型、III型白斑)和高危组(IV型、V型、VI型白斑)。然后所有患者均于全麻支撑喉镜下行喉显微手术,术后切除的病变组织送病理检查,将NBI内镜评估结果与病理结果进行比较,计算NBI内镜评估病变性质的敏感性、特异性、准确性及Kappa-Cohen指数。结果153侧病变中,根据NBI内镜,123侧病灶(80.4%)评估为低危组(I型18侧,II型41侧,III型64侧),可能为良性病变,30侧病灶(19.6%)评估为高危组(IV型2侧,V型25侧,VI型3侧),可能为恶性;病理结果示121侧(79.1%)为低危组(角化过度20侧,轻度不典型增生39侧,中度不典型增生62侧),32侧(20.9%)为高危组(重度不典型增生5侧,原位癌22侧,浸润癌5侧)。NBI内镜评估除低危组中有2侧III型病变病理检查为重度不典型增生外,其余均与病理结果相符合。NBI内镜预测白斑恶性程度的敏感性为100%,特异性为97.6%,阳性预测值为90%,阴性预测值为100%,准确性为98%,Kappa-Cohen指数为90%(95%置信区间82.3%~100%)(P<0.05)。结论根据NBI内镜可较准确评估声带白斑的病变性质。

声带白斑术后复发影响因素探究及预测模型的建立

目的研究声带白斑术后复发的影响因素并建立临床预测模型。方法回顾性分析2016年2月~2020年2月手术治疗的声带白斑患者386例的临床资料。根据随访结果,将患者分为复发组(89例)和未复发组(297例),应用单因素分析和Logistic回归分析筛选出声带白斑术后复发的影响因素,建立Logistic风险预测模型,并采用R软件以Boostrap法对模型进行内部验证。结果年龄(OR=1.082)、饮酒(OR=1.946)、滥用嗓音(OR=2.436)、咽喉反流(OR=2.054)、中度异型增生(OR=2.383)和重度异型增生/原位癌(OR=3.304)是声带白斑术后复发的影响因素。模型的内部验证AUC为0.777,95%CI为0.663~0.825,模型拟合度较好。结论声带白斑术后复发与患者年龄、白斑范围、病理形态、咽喉反流等有关。