Predicting the Activity of Oral Lichen Planus with Glycolysis-related Molecules:A Scikit-learn-based Function

Objective Oral lichen planus(OLP)is one of the most common oral mucosa diseases,and is mainly mediated by T lymphocytes.The metabolic reprogramming of activated T cells has been shown to transform from oxidative phosphorylation to aerobic glycolysis.The present study investigated the serum levels of glycolysis-related molecules(lactate dehydrogenase,LDH;pyruvic acid,PA;lactic acid,LAC)in OLP,and the correlation with OLP activity was assessed using the reticular,atrophic and erosive lesion(RAE)scoring system.Methods Univariate and multivariate linear regression functions based on scikit-learn were designed to predict the RAE scores in OLP patients,and the performance of these two machine learning functions was compared.Results The results revealed that the serum levels of PA and LAC were upregulated in erosive OLP(EOLP)patients,when compared to healthy volunteers.Furthermore,the LDH and LAC levels were significantly higher in the EOLP group than in the nonerosive OLP(NEOLP)group.All glycolysis-related molecules were positively correlated to the RAE scores.Among these,LAC had a strong correlation.The univariate function that involved the LAC level and the multivariate function that involved all glycolysis-related molecules presented comparable prediction accuracy and stability,but the latter was more time-consuming.Conclusion It can be concluded that the serum LAC level can be a user-friendly biomarker to monitor the OLP activity,based on the univariate function developed in the present study.The intervention of the glycolytic pathway may provide a potential therapeutic strategy.

Prediction of potential targets and molecular mechanisms of Tripterygium hypoglaucum for oral lichen planus based on network pharmacology and molecular docking

Objective:To explore the potential targets and molecular mechanisms of tripterygium hypoglaucum for oral lichen planus(OLP)by applying network pharmacology and molecular docking technology.Methods:The active ingredients and targets of tripterygium hypoglaucum were screened.OLP-related targets were predicted.The Protein-Protein Interaction(PPI)network was constructed for the intersection targets of tripterygium hypoglaucum and OLP.The“OLP-target-molecule-Tripterygium hypoglaucum”network was constructed and visualized.The intersection genes were screened for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.Molecular docking analysis and visualization were performed.Results:15 active ingredients and 78 targets of tripterygium hypoglaucum were obtained.9109 OLP-related targets were screened,and 54 intersection genes of tripterygium hypoglaucum with OLP were obtained.The top 10 key targets were screened from the constructed PPI network.The top 10 active ingredients of tripterygium hypoglaucum were screened from the constructed“OLP-targets of actionactive ingredients-tripterygium hypoglaucum”network.The GO and KEGG analyses of the 54 intersection targets indicated that tripterygium hypoglaucum may play a therapeutic role by regulating one carbon pool by folate,pathways in cancer,et al.Molecular docking analysis showed that dihydrofolate reductase(DHFR),phosphoribosylglycinamide formyltransferase(GART),estrogen receptor 1(ESR1),et al are the key targets for the treatment of OLP in tripterygium hypoglaucum.Conclusion:The potential key targets and molecular mechanisms of tripterygium hypoglaucum in treating OLP provide a theoretical basis for new drug development and clinical applications.

Unilateral lichen planus with Blaschko line distribution: A case report

BACKGROUND Lichen planus(LP)with distribution of lesions along Blaschko’s lines is a rare entity,accounting for 0.24%-0.62%of all patients.Unilateral distribution of lesions in arm,leg,trunk,and waist is even less common.Approximately 10%of patients with LP manifest nail lesions.CASE SUMMARY A 20-year-old woman presented to our department with polygonal,purpuric,flattopped papules over the right arm,right leg,and right side of trunk and waist for the last 5 mo.The patient initially developed nail deformation in the left middle finger with no obvious cause,followed by development of blue-purple and red maculopapular rash with pruritus.During the disease course,the skin lesions aggravated and spread to several segments due to scratching.The lesions showed unilateral distribution along the Blaschko’s lines.The diagnosis of LP along Blaschko’s lines was established based on dermoscopy and skin biopsy.Her cutaneous lesions considerably improved after 4-wk treatment with intramuscular glucocorticoid,oral acitretin,topical glucocorticoid,and retinoids.CONCLUSION Cases of LP involving multiple segments of the body along the Blaschko’s lines with nail damage are rare.

Periodontopathogen profile of healthy and oral lichen planus patients with gingivitis or periodontitis

Oral lichen planus （OLP） is a chronic inflammatory disease that is frequently detected in oral tissues. The aim of our study was to identify the prevalence of the detection of periodontopathogenic microorganisms （Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia and Treponema denticola in OLP patients and to compare with this prevalence of periodontopathogenic microorganisms in healthy non-OLP patients. Our study included 27 （18 chronic periodontitis （OLPP） and 9 gingivitis （OLPG）） patients diagnosed with OLP along with 26 （13 chronic periodontitis （HP） and 13 gingivitis （HG）） healthy non-OLP patients. The multiplex polymerase chain reaction （PCR）with subsequent reverse hybridization method （micro-IDent） was used for identifying periodontopathogenic microorganisms present in subgingival plaque samples. The percentages of detection for A. actinomycetemcomitans, P. gingivalis, P. intermedia, T. forsythia and T. denticola in subgingival plaque samples taken from OLP patients （OLPG and OLPP） were 18.5%, 85.1%, 81.4%, 88.8% and 74%, respectively. Meanwhile, in the non-OLP patients （HG and HP）, these values were 7.6%, 50%, 46.1%, 73% and 57.7%, respectively. Thus, comparing the non-OLP groups with the OLP groups, the periodontopathogens＇ percentages of detection in the OLP groups were higher than those in the non-OLP groups. According to our study results, OLP patients have higher levels of infection with A. actinomycetemcomitans, P. gingivalis, P. intermedia, T. forsythia and T. denticola than non-OLP patients. We argue that the high percentages in patients with OLP may help identify the importance of periodontopathoRenic microorganisms in the progress of periodontal diseases of OLP.

Interferon-c and interleukin-4 detected in serum and saliva from patients with oral lichen planus

Our previous salivary study had demonstrated an apparent T helper 2 （Th2）-predominance in saliva of oral lichen planus （OLP） patients and suggested a potential of salivary interleukin-4 （IL-4） as a biomarker for monitoring disease severity. To further determine the consistency of Th1/Th2 bias of OLP, this study investigated the expression profile of interferon-γ （IFN-γ） and IL-4 in serum and the relationship of the serum levels of these cytokines with their saliva partners. Sixty ethnic Chinese patients with OLP （40 of the erythematous/ulcerative form and 20 of the reticular form） were recruited for this study, with 40 age-sex-matched healthy volunteers as control group. IFN-γ and IL-4 levels in serum and paired saliva samples were screened by enzyme-linked immunosorbent assay. OLP patient showed a low-level IFN-γ but high-level IL-4 expression profile in both serum and saliva, with a lower IFN-γ/IL-4 ratio. Serum IL-4 level in the erythematous/ulcerative group was significantly higher than that in the reticular group. Serum levels of IFN-γ and IL-4 were significantly and positively correlated with their saliva partners. These results provided more evidence for Th2 cytokine- predominant immune imbalance in OLP, as well as the potential of IL-4 as the biomarker for monitoring severity of OLP.

Implications of Th1 and Th17 Cells in Pathogenesis of Oral Lichen Planus

Oral lichen planus （OLP） is considered a T cell-mediated autoimmune disease with unknown aetiology. T helper cells appear to play an important role in the pathogenesis of OLP. We investigated the possible role of T helper cells, Th1 and Th17, in the lesions and circulation of patients with OLP. Forty patients with OLP and 15 healthy volunteers were recruited. Double immunofluorescence staining was used to detect Th1 and Th17 cells in the OLP lesions, and intracellular cytokine staining and flow cytometry to evaluate the proportion of Th1 and Th17 cells in peripheral blood. The levels of serum interferon （IFN）-γ and interleukin （IL）-17 were assessed by using an enzyme-linked immunosorbent assay. It was found that Th17 cells, as well as Th1 cells, were present in OLP lesions. The proportion of peripheral Th1 and Th17 cells was significantly increased in patients with OLP. The proportion of Th17 cells in atrophic-erosive OLP was elevated as compared with that in reticular OLP. Serum IL-17 levels in OLP patients were significantly higher than in controls, and those in the atrophic-erosive OLP group were increased as compared with the reticular OLP group. However, the levels of serum IFN-γ were slightly decreased in OLP patients. Our data suggested that Th1 and Th17 cells in the local lesions and peripheral blood may be associated with the pathogenesis of OLP, and that IL-17 may be an important proinflammatory cytokine in OLP. These findings enhance our understanding of OLP pathogenesis.

Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis

The Merkel cell-neurite complex initiates the perception of touch and mediates Ap slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry （the avidin-biotin-peroxidase complex and double immunofluorescence methods）using pan cytokeratin, cytokeratin 20 （K20, a Merkel cell marker）, and neurofilament 200 （NF200, a myelinated Aβ- and Aδ-nerve fibre marker） antibodies. N F200-immunoreactive （ir） nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hvperkeratosis.

The Prevalence of Hepatitis C Virus Infection in Oral Lichen Planus in an Ethnic Chinese Cohort of 232 Patients

Aim Oral lichen planush （OLP） is a chronic inflammatory disease, and has been reported to have a correlation with hepatitis Cvirus （HCV） infection in some regional investigations. In this study, we investigated the prevalence of HCV in patients with oral lichen planus in an ethnic Chinese cohort. Methodology The antibody of HCV infection was detected by using enzymelinked immunosorbent assay. Moreover, the clinical characteristics of whole the cohort have also been studied, such as the gender, age, clinical type, habits and social factors. Results Of all 232 patients, the antibody of HCV infection was detected positive in 4 patients （1.72%） using enzyme-linked immunosorbent assay. It was lower than that in control group of 2.5%, but not significant （P=0.309）. The positive rate of HCV antibody in the erosive type ones （4.2%） was higher than that in the reticular type ones （1.0%）, but this difference was proved to be not significant （P=0.389）. The clinical characteristics of whole cohort, such as the gender, age, clinical type, habits and social factors, showed the outcome obtained in the present study were similar to thao of our previous study. Conclusion HCV may play no etiological role in oral lichen planus in ethnic Chinese OLP patients.

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.

The Expression of TNF-α and ICAM-1 in Lesions of Lichen Planus and Its Implication

In order to investigate the role of TNF-α and ICAM-1 in the pathogenesis of lichen planus, immunohistochemistry was used to detect the expression of TNF-α and ICAM-1 in skin lesions of the patients with lichen planus and skin tissues of normal subjects. The results showed that positive rates of TNF-α and ICAM-1 expressions in lichen planus were significantly higher than those in normal skins （both P〈0.05）. Meanwhile, there was a obvious correlation between the increase of TNF-α and that of ICAM-1 in lichen planus. The expression of TNF-α and ICAM-1 might play an important role in the development of lichen planus.

Expression of Apoptosis Related Protein in Skin Lesions of Lichen Planus and Its Implication

In order to investigate the role of Caspase-3 and Bax in the pathogenesis of lichen planus, immunohistochemistry was used to detect the expression of Caspase-3 and Bax in skin lesions of the patients with lichen planus and skin tissues of normal subjects. The results showed that positive rate of Caspase-3 and Bax expression in lichen planus were significantly higher than that in normal skins （both P〈0.05）. Meanwhile, there was a obvious correlation between the increase of Caspase-3 and that of Bax in lichen planus. The expression of Caspase-3 and Bax might play an important role in the development of lichen planus.

Treatment of cutaneous lichen planus with ALA-mediated topical photodynamic therapy

Purpose:To evaluate the efectiveness of topical 5-aminolevulinie acid(ALA)-mediated pho-todynamic therapy(PDT)for the treatment of cutaneous lichen planus(LP).Methods:A total of 17 symptomatic LP lesions in 7 Chinese patients were assessed.ALA cream(10%)was applied topically to LP lesions for 3h.The lesions were iradiated with a 635 nm diode laser at the dose level of 100J/cm^(2).The treatment was repeated at two week intervals.Clinical assessmnent was conducted before each treatment.Follow-up was performed once a month for up to six months.Results:Lesions showed significant improvement after one to four courses of treatments.Complete response was achieved in 13 lesions(five patients)and partial remission in four lesions(two patients).The complete response rate was 71%.There was no significant side ffects except the feeling of pain that most patients could tolerate.Follow-up of five patients who achieved complete response showed no signs of recurrence.Conclusion:Topical ALA PDT is effective in the treatment of cutaneous LP.

Comparative Observation on the Effects of Radix Tripterygium Hypoglaucum Tablet and Tripterygium Glycosides Tablet in Treating Erosive Oral Lichen Planus

Objective: To compare the therapeutic effects of Radix Tripterygium hypoglaucum tablet (THT) and Tripterygium glycosides tablet (TGT) in treating erosive oral lichen planus(EOLP).Methods: The patients were randomized into two groups, and they were treated with THT (n=47) or TGT (n=47), respectively. The therapeutic effects were evaluated after 3 months treatment.Results: For the patients of grade 1, the total efficacy in TGT group was 85.71%, compared with 52.38% in THT group, the efficacy was statistically greater in the group receiving TGT (P=0.043). However, for the patients of grade 2, the difference was not statistically significant (P=0.173).Conclusion: TGT is more effective in treating EOLP than THT for grade 1 patients. However, TGT is not suitable for patients of child bearing age.

Lichen planus affecting a 12-year-old girl

Lichen planus (LP) is a chronic inflammatory mucocutaneous condition which is relatively common in adults but rarely affects children. In addition, few cases with oral lesions affecting children have been reported in the literature. The purpose of this study is to report an unusual case of oral LP involving the tongue and buccal mucosa in a child. A 12-year-old girl complained of painless oral lesions with 18 months of evolution. On clinical evaluation, multiple white lesions in tongue and buccal mucosa were observed with no cutaneous lesions. Diagnosis was made based on clinical examination and histopathological features. No active treatment was necessary. The patient is currently under regular evaluation. Although rarely reported in childhood, lichen planus should be considered in a differential diagnosis of hyperkeratotic and/or reticular lesions of the oral mucosa in children.

Esophageal lichen planus:Current knowledge,challenges and future perspectives

Lichen planus(LP)is a frequent,chronic inflammatory disease involving the skin,mucous membranes and/or skin appendages.Esophageal involvement in lichen planus(ELP)is a clinically important albeit underdiagnosed inflammatory condition.This narrative review aims to give an overview of the current knowledge on ELP,its prevalence,pathogenesis,clinical manifestation,diagnostic criteria,and therapeutic options in order to provide support in clinical management.Studies on ELP were collected using PubMed/Medline.Relevant clinical and therapeutical characteristics from published patient cohorts including our own cohort were extracted and summarized.ELP mainly affects middle-aged women.The principal symptom is dysphagia.However,asymptomatic cases despite progressed macroscopic esophageal lesions may occur.The pathogenesis is unknown,however an immune-mediated mechanism is probable.Endoscopically,ELP is characterized by mucosal denudation and tearing,trachealization,and hyperkeratosis.Scarring esophageal stenosis may occur in chronic courses.Histologic findings include mucosal detachment,T-lymphocytic infiltrations,epithelial apoptosis(Civatte bodies),dyskeratosis,and hyperkeratosis.Direct immuno-fluorescence shows fibrinogen deposits along the basement membrane zone.To date,there is no established therapy.However,treatment with topical steroids induces symptomatic and histologic improvement in two thirds of ELP patients in general.More severe cases may require therapy with immunosuppressors.In symptomatic esophageal stenosis,endoscopic dilation may be necessary.ELP may be regarded as a precancerous condition as transition to squamous cell carcinoma has been documented in literature.ELP is an underdiagnosed yet clinically important differential diagnosis for patients with unclear dysphagia or esophagitis.Timely diagnosis and therapy might prevent potential sequelae such as esophageal stenosis or development of invasive squamous cell carcinoma.Further studies are needed to gain more knowledge about the pathogenesis and treatment options.

Dysregulation of Notch signaling related genes in oral lichen planus

Objective: To investigate a dysregulation of Notch signaling in oral lichen planus(OLP)using public available microarray dataset.Methods: A m RNA expression profiling dataset from Gene Expression Omnibus was downloaded. Differential gene expression between OLP and normal oral epithelium was examined using Network Analyst. The dysregulated genes related to Notch signaling were identified.Results: Thirteen genes in Notch signaling pathway were significantly differential expressed between OLP and normal epithelium. OLP samples significantly increased the m RNA levels of HEYL, APH1 B, CNTN1 and PSEN2. Whilst, ITCH, HES1, TLE2, DLK2,DTX2, NOTCH3, JAG2, RFNG, and SPEN were downregulated in OLP groups.Conclusions: Notch signaling was dysregulated and may participate in pathophysiologic process in OLP.

Treatment of oral lichen planus by surgical excision and acellular dermal matrix grafting:Eleven case reports and review of literature

BACKGROUND Oral lichen planus(OLP)is a chronic inflammatory disorder,and it can affect normal oral function.The conventional treatments for OLP are not always effective,and relapse easily occurs.Therefore,treatment of OLP is difficult and challenging.In this study,we evaluated over a long period the clinical efficacy of surgical excision and acellular dermal matrix(ADM)grafting in patients with refractory OLP.CASE SUMMARY Eleven patients with refractory OLP underwent a standardized protocol of surgical excision and ADM grafting.The condition of the area of the grafted wound,the intraoperative maximum mouth opening,pain,and clinical healing were assessed at postoperative follow-up visits.All patients had a flat surgical area with similar mucosal tissue coverage and local scar formation.Patients had no irritation and pain in their mucous membranes when eating acidic and spicy food.All patients’mouth openings returned to normal within 2-6 mo after surgery.During follow-up,none of the patients had recurrence of OLP after surgery.The longest follow-up was 11 yr and the shortest was 6 mo,and none of the patients relapsed during follow-up.CONCLUSION Surgical excision and ADM grafting could be an effective method to treat refractory OLP.

A Retrospective and Comparative Study of Familial and Non-familial Bullous Lichen Planus

In order to compare the clinical characteristics of familial and non-familial bullous lichen planus (BLP), the archival data of 36 BLP patients with positive family history and 21 BLP patients with negative family history diagnosed according to the clinical features and histopathology were collected in our department from 1956 to 2003. The clinical features were analyzed and compared. There were significant differences between familial and non-familial BLP in age of onset, duration of disease and extension of eruption (P<0.01). It was concluded that familial BLP appeared to differ from the non-familial form in its earlier age of onset, longer duration of the disease, more extensive eruption and more tendency to involve nails. Hereditary factors may play a role in the pathogenesis of familial BLP.

Histopathological and Immunohistochemical Study of the Distinction between Oral Lichen Planus and Oral Lichenoid Lesions

Background: Oral potentially malignant disorders, which include oral lichen planus (OLP), are clinical presentations that carry a risk of development to cancer in the oral cavity. Oral lichenoid lesions (OLLs) are also termed interface/lichenoid mucositis. Malignant transformation of them remains controversial, but distinct clinical and histological criteria for how to differentiate OLP from OLLs have not been developed. Objectives: The purpose of this study was to elucidate findings that can allow histopathological differentiation of OLP and OLLs using histomorphological and immunohistochemical analyses. Materials and Methods: Analyses were performed in 10 cases diagnosed with OLP and 9 cases diagnosed with OLLs. Cytokeratin 19 (CK19), Ki-67 and CD3 were used as primary antibodies to detect basal cells, proliferative activity and T-cell distribution, respectively, and Perlecan and COX-2 to evaluate epithelial intracellular arrangements and interstitial distributions of proteoglycans and enzymes. Results: For CK19, positive cells were significantly found in OLLs at both the prominent area and site adjacent to the lesion comparison with those of OLP’s. The number of COX-2 positive cells was significantly higher in spinous and basal layers in OLLs of the prominent area. Additionally, OLLs showed mild to moderate expression for perlecan in the basal to spinous layers and in subepithelial tissue. Conclusion: Almost no basal cells were noted in the prominent area in OLP. COX-2 and perlecan were found in the basal to spinous layers in OLLs. Although there are restrictions, these suggested the possibility of helping to distinguish between OLP and OLLs.

Major Clinical Features and Epidemic Characteristics of Erosive Vulvar Lichen Planus:A Retrospective Analysis

Objective:Vulvar lichen planus(VLP),especially erosive VLP(EVLP),seriously affects women’s physiological function and quality of life.A retrospective analysis of erosive vulvar lichen planus(EVLP)was performed to raise awareness on this chronic,deforming,and painful vulvar disease.Methods:This observational retrospective study involved 40 patients with EVLP among 1,368 patients with vulvar disease from 2017 to 2020.The patients’vulvar clinical features and extravulvar mucosal involvement were investigated.The patients’pain and quality of life were evaluated with the numeric rating scale and the Dermatology Life Quality Index(DLQI),respectively.Clinical characteristics were reported using frequencies and proportions for categorical variables.Continuous variables are expressed as mean±standard deviation.The association between NRS score for pain and DLQI score was analyzed by Pearson’s correlation test.Results:EVLP accounted for 2.9%(40/1,368)of all cases of vulvar disease,and the median age at onset was 42 years.Erosion mostly occurred on the labia minora and introitus.Half(20/40)of the patients had extravulvar mucosal involvement.Seventeen(42.5%)patients had oral lichen planus,and seven(17.5%)patients were diagnosed with vulvovaginal-gingival syndrome.The numeric rating scale score showed that 47.5%(19/40)of patients experienced mild pain,whereas 12.5%(5/40)described the pain as severe.Thirty-one patients(77.5%,31/40)had dyspareunia,and nine patients had aggravated pain after sexual intercourse.The mean DLQI score was 9.1±6.0,with 37.5%(15/40)of patients indicating that EVLP had severely affected their lives.The numeric rating scale score for pain was significantly correlated with the DLQI score(P=0.007).Conclusion:EVLP can affect the quality of women’s lives and cause severe deformations and painful architectural changes.The description of the characteristics of EVLP in this report will benefit the diagnosis and early treatment of this disease.