Multidrug dissolvable microneedle patch for the treatment of recurrent oral ulcer

Recurrent oral ulcer is a painful oral mucosal disorder that affects 20%of the world’s population.The lack of a radical cure due to its unknown underlying cause calls for innovative symptomatic treatments.This work reports a hyaluronic acid-based dissolvablemicroneedle patch(ROUMNpatch,short for recurrent oral ulcer microneedle)loaded with dexamethasone acetate,vitamin C and tetracaine hydrochloride for the treatment of recurrent oral ulcers.The ROUMN patch shows enhancement in both the anti-inflammatory effect elicited by dexamethasone and the pro-proliferation effect of vitamin C.In vitro experiments show that ROUMN has a higher efficiency in suppressing lipopolysaccharide(LPS)-induced interleukin-6(IL-6)expression than dexamethasone alone.Cell proliferation and migrationwere also significantly promoted byROUMNcompared to vitamin C alone.The healing-promoting effect of ROUMN was also verified in vivo using an acetic acid-cauterized oral ulcer model in rats.ROUMN as a treatment accelerated the healing process of oral ulcers,shortening the total healing time to 5 days compared with the 7 days required by treatment using watermelon frost,a commonly used over-the-counter(OTC)drug for oral ulcers.The rapid dissolution of the hyaluronic acid-based microneedles and the superior healing-promoting effect of the drug combination could lead to a broad application prospect of the ROUMN patch in the treatment of recurrent oral ulcers.

Metabolomics characterization of Qingwei San on oral ulcer in db/db mice with stomach heat pattern

Objective:To characterize the effects of Qingwei San(QWS)on diabetic oral ulcer(OU)mice with stomach heat pattern through metabolomic analysis.Methods:A stomach heat pattern mouse model was established by treating C57BLKS/J Leprdb/db(db/db)mice with dried Zingiber officinale Rosc.rhizome(Z.officinale,Gan Jiang)decoction by gavage.All model mice had blood glucose levels of≥11.1 m M.Subsequently,OU was induced by Na OH cauterization.After 1 week of administration of QWS,non-targeted metabolomic analysis of serum was conducted using ultra high performance liquid chromatography coupled with mass spectrometry(UHPLC-MS/MS).Results:The non-targeted metabolomics results indicated that tryptophan metabolism,2-oxocarboxylic acid metabolism,serotonergic synapses,amino sugar and nucleotide sugar metabolism,and amino acid biosynthesis were involved in the therapeutic effects of QWS,with tryptophan metabolism playing a predominant role.Conclusion:QWS treatment can significantly improve the pathological status of diabetic OU mice with stomach heat pattern.QWS may regulate the release of inflammatory factors through the tryptophan metabolism pathway.

New therapy for oral ulcer:Evodia rutaecarpa patch combined with acupoint application

Background:Oral ulcer is the most common and easily recurrent disease in stomatology,which influence the patients’communication,normal dietary,and sleep.Evodia rutaecarpa(ER)is a traditional Chinese herbal medicine recorded in ancient Chinese medical books,which has a medicinal history of more than 2,000 years.Clinically,the application of ER at plantar Yongquan point(KI1)is effective in the treatment of oral ulcer.The purpose of this study was to combine the modern transdermal drug delivery system with traditional Chinese medicine to develop the transdermal absorption patch of ER and apply it to the treatment of oral ulcer at Yongquan point of plantar.Methods:Firstly,the medicinal materials of ER were extracted and the extracted materials were prepared into dispersed ER patch.The formulation and preparation process were screened by orthogonal design method and single factor investigation method.The adhesive and transdermal properties of the patch were used as the evaluation index of the preparation.Secondly,Wistar rats were used as experimental animals to establish a rat model of mouth ulcers.Wistar rats were randomly divided into normal group,model group(A),model group(B),low dose group,medium dose group and high dose group.the efficacy of ER on rat’s oral ulcer model was evaluated through three aspect such as apparent index,pathological index and biochemical index.Results:The patch had suitable adhesion and good skin penetration,which was an effective treatment for oral ulcer.In vivo pharmacodynamic studies,compared with the normal group,the body mass and food intake of rats in each group after modeling decreased,the amount of drinking water increased,the tissue structure of oral mucosa was damaged,and the levels of inflammatory factors(TNF-α,IL-6)and malondialdehyde increased,the levels of anti-inflammatory factors(IL-10),cell growth factor(epidermal growth factor,TGF-β_(1))and superoxide dismutase decreased.Compared with the model group,the body weight and food intake of each dosing group increased,water consumption decreased,the oral mucosal tissue structure was more complete,the levels of TNF-α,IL-6 and malondialdehyde decreased,the levels of IL-10,epidermal growth factor,TGF-β1 and superoxide dismutase increased,and the changes of various indexes were dose-related.Conclusion:ER patch can inhibit inflammatory reaction,enhance the antioxidant defense ability of the body,and promote the repair of damaged oral mucosa,so as to play an effective role in the treatment of oral ulcer.

Experimental Study of Emilia Sonchifolia Combined with Coptidis Rhizoma for the Prevention and Treatment of Oral Ulcer

Objective: This paper aims to investigate the therapeutic effect of the combination of Emilia Sonchifolia and Coptidis Rhizoma on oral ulcer rats. Methods: 36 SD rats of half male and half female were kept for 7 days, and 6 rats among them were selected as normal group by random sampling method, and the rest rats were randomly divided into model group, positive control group, Emilia Sonchifolia group, Coptidis Rhizoma group and combined group after the establishment of oral ulcer model. The normal group and model group were given blank film, the positive control group was given Guilin Watermelon Frost, and the Emilia Sonchifolia group, Coptidis Rhizoma group and combined group were given the corresponding oral film, which was administered to the ulcer for 7 days continuously, 2 times per day. The healing of oral ulcer was assessed at the end of the last day of administration, and the ulcer area was calculated on the 1st, 3rd, 5th and 7th days after successful modeling, and the serum levels of IL-2 and TNF-α in rats were detected by Emilia Sonchifolia. Results: The grading of ulcer healing in the positive control group and the combined group was better than the other groups, and the difference was statistically significant when compared with the model group (p Coptidis Rhizoma group, Emilia Sonchifolia group, combined group and positive control group was smaller than that in the model group, and the difference was statistically significant (p Emilia Sonchifolia group, Coptidis Rhizoma group and combined group were all effective in reducing the area of oral ulcer, among which the combined group was more effective. The level of pro-inflammatory factor TNF-α was reduced and the level of anti-inflammatory factor IL-2 was increased in the Emilia Sonchifolia group, Coptidis Rhizoma group and combined group, and the difference was statistically significant (p Conclusion: The combination of Coptidis Rhizoma and Emilia Sonchifolia is effective in the treatment of oral ulcer in rats, and the effect of the combination is better than that of the drug alone.

Effect and mechanism of persimmon leaf flavonoid treatment of experimental oral ulcer

OBJECTIVE To explore the therapeutic effect and its mechanism of persimmon leaf flavonoids(PLF) on rats with oral ulcer. METHODS The oral ulcer model was induced by acetic acid,was used for intervention of Guilin watermelon frost and different dose(20,40 and 80 mg·kg^(-1)) of PLF.Ulcer area was calculated on the fourth and the seventh day after injury; the changes of superoxide dismutase(SOD) and malondialdehyde(MDA) in serum and ulcer tissues were observed; the level of tumor necrosis factor alpha(TNF-alpha) in ulcer tissue was measured. To observe the pathological morphological changes of H-E staining. RESULTS Guilin watermelon frost and PLF(40 and 80 mg·kg^(-1))can reduce the ulcer area(P<0.05); PLF(20,40 and 80 mg·kg^(-1)) can increase the activity of SOD and decrease the content of MDA in serum and ulcer tissue(P<0.05); Guilin watermelon frost and PLF could significantly decrease the levels of TNF-alpha in ulcer tissue(P<0.05),and improve the inflammatory infiltration of ulcer tissue. CONCLUSION PLF has certain therapeutic effects on oral ulcer induced by acetic acid,and the mechanism may be related to improve oxidative damage and reduce inflammatory reaction.

Treatment of oral ulcer based on TCM syndrome differentiation

Oral ulcer is a kind of ulcerative injury that occurs in the oral mucosa and is very common in clinic.In severe case,it can affect the quality of life of the patients.Western medicine treatment of oral ulcer is often prone to relapse,while the effect of traditional Chinese medicine treatment is remarkable.

Test Case Analysis Application of Jiawei-yinhuo Soup the Treatment of Recurrent Oral Ulceration

Recurrent oral ulceration,which is small but not easy to cure,seriously affects the quality of life of the patients.This paper analyzes professor Wang Xiaoyan's application of Yinhuotanghuacai to treat oral ulcer with floating of yang in deficiency condition,which can significantly improve the clinical symptoms of patients and improve the quality of life of patients.

Treatment of Oral Ulcer based on TCM Syndrome Differentiation

Oral ulcer is a kind of ulcerative injury that occurs in the oral mucosa and is very common in clinic.In severe case,it can affect the quality of life of the patients.Western medicine treatment of oral ulcer is often prone to relapse,while the effect of traditional Chinese medicine treatment is remarkable.

Oral ulcerations as the first manifestations of acute leukemia: A case report

Acute myeloblastic leukemia (AML) is a highly fatal malignant bone marrow disease. Physicians, dentists and all other healthcare professionals should be aware of sinister oral signs and symptoms in order to early diagnosis and referral of patients. Here we report a case of AML who presented with oral ulcers. Ulcers developed after a parrot bite, which initially misled the physicians. Unfortunately our patient did not survive, but early diagnosis and prompt investigation and treatment can be life-saving in many other similar cases.

Formulation of a new phenytoin-containing mucoadhesive and evaluation of its healing effects on oral biopsy ulcers

Background and Objective: Several studies have shown the wound healing effect of topical phenytoin, which is applied by its effect on connective tissue intracellular matrix. However, there are still some controversies about its effect on various kinds of wounds, especially in the experimental models. This study is aimed at evaluating the effect of mucoadhesive paste compared to phenytoin mucoadhesive paste on wound healing after oral biopsy. Material and Methods: In this double blind randomized clinical trial, 20 patients who were eligible for oral biopsy were allocated into the case and control groups. After the biopsy, patients having ulcers ranging between one and two centimeters were treated by simple or 1% phenytoin mucoadhesive paste. All patients were instructed to apply their paste at least three times a day for five days after the biopsy. Patients in both groups were evaluated every other day for size of the ulcer, degree of pain and diameter of the inflammatory halo. Statistical analysis was done using SPSS software and Mann-Whitney test. Results: After the second and third appointments, it was observed that the rate of wound healing and decrease in the size of the ulcers were significantly quicker in the treatment group (p = 0.001 and p = 0.003 respectively) and the patients in the phenytoin group reported less pain. Diameter of the inflammatory halo was not significantly different between two groups. Conclusion: Applying 1% phenytoin mucoadhesive paste on biopsy ulcers resulted in accelerated wound healing and decrease in pain, but had no effect on the diameter of the inflammatory halo.

A head to head comparison of oral vs intravenous omeprazole for patients with bleeding peptic ulcers with a clean base,flat spots and adherent clots

AIM: To compare the effect of intravenous and oral omeprazole in patients with bleeding peptic ulcers with- out high-risk stigmata. METHODS: This randomized study included 211 pa- tients [112 receiving iv omeprazole protocol (Group 1), 99 receiving po omeprazole 40 mg every 12 h (Group 2)] with a mean age of 52.7. In 144 patients the ulcers showed a clean base, and in 46 the ulcers showed flat spots and in 21 old adherent clots. The endpoints were re-bleeding, surgery, hospital stay, blood transfusion and death. After discharge, re-bleeding and death were re- evaluated within 30 d. RESULTS: The study groups were similar with respect to baseline characteristics. Re-bleeding was recorded in 5 patients of Group 1 and in 4 patients of Group 2 (P = 0.879). Three patients in Group 1 and 2 in Group 2 underwent surgery (P = 0.773). The mean length of hospital stay was 4.6 ± 1.6 d in Group 1 vs 4.5 ± 2.6 d in Group 2 (P = 0.710); the mean amounts of blood transfusion were 1.9 ± 1.1 units in Group 1 vs 2.1 ± 1.7 units in Group 2 (P = 0.350). Four patients, two in each group died (P = 0.981). After discharge, a new bleed- ing occurred in 2 patients of Group 1 and in 1 patient of Group 2, and one patient from Group 1 died. CONCLUSION: We demonstrate that the effect of oral omeprazole is as effective as intravenous therapy in terms of re-bleeding, surgery, transfusion requirements, hospitalization and mortality in patients with bleeding ulcers with low risk stigmata. These patients can be treated effectively with oral omeprazole.

Novel oral-targeted therapies for mucosal healing in ulcerative colitis

Ulcerative colitis(UC), a chronic, relapsing, remitting disease of the colon and rectum, is characterized by inflammatory ulceration of the mucosa. Current UC therapy relies on controlling acute episodes and preventing relapse. To predict modifications in the natural course of UC, mucosal healing(MH) has emerged as a major treatment goal. Endoscopic evaluation is considered the gold standard for assessing MH, which can be achieved by conventional drugs and biologics in many, but not all, patients. Consequently, interest is focusing on the development of new substances for UC therapy, and new oral agents are in the pipeline. This review will focus on the ability of newly developed oral drugs to induce and maintain MH in UC patients.

复发性口腔溃疡患者食物不耐受特异性IgG抗体检测特征分析

目的分析复发性口腔溃疡(ROU)患者食物不耐受特异性免疫球蛋白G(IgG)抗体检测特征结果,以期为ROU患者对食物不耐受的诊断和治疗提供依据。方法采用回顾性分析,选取2020年1月至2023年12月在郑州大学第一附属医院门诊就诊的1975例ROU患者为研究对象,收集患者的一般资料,统计患者食物不耐受特异性IgG抗体检测结果,比较不同年龄、不同性别患者食物不耐受的抗体检测结果差异。结果血清IgG阳性率最高的前5种食物分别是鸡蛋(47.34%)、牛奶(31.14%)、小麦(21.87%)、大豆(21.22%)、西红柿(10.38%),其中牛肉(0.46%)、猪肉(0.56%)、鸡肉(1.37%)、虾(1.82%)的血清IgG阳性率较低。女性受试者对鳕鱼、鸡蛋、牛奶3种食物的不耐受阳性率显著高于男性,差异有统计学意义(P<0.05)。不同年龄患者在鸡肉、鳕鱼、鸡蛋、蘑菇、牛奶、虾、大豆、小麦8种食物中的不耐受阳性率差异有统计学意义(P<0.05);未成年组对鸡蛋、牛奶、大豆、小麦4种食物的不耐受阳性率高于中青年组和老年组,对虾、蘑菇的不耐受阳性率低于中青年组和老年组,对鸡肉的不耐受阳性率显著高于中青年组,对鳕鱼的不耐受阳性率显著高于老年组,差异有统计学意义(P<0.05)。结论ROU患者发生食物不耐受的概率较高,食物不耐受与患者的性别和年龄有一定关系,及早对ROU患者进行食物血清特异性IgG抗体检测,可及时发现患者不耐受的食物以调整饮食,避免食源性的机体免疫反应。

对大剂量甲氨蝶呤化疗患儿增加口腔护理的效果研究

分析增加口腔护理对大剂量甲氨蝶呤化疗后口腔溃疡的护理效果。选取2022年5月1日—2023年3月28日贵州省人民医院儿科收治的76例急性淋巴细胞白血病患儿为研究对象,所有患儿均接受大剂量甲氨蝶呤化疗,用随机数字表法将患儿平均分为对照组38例,行常规护理,观察组38例,增加口腔护理,比较两组患儿情绪状态、生活质量、干预效果、口腔黏膜分级情况和自护能力。研究发现,大剂量甲氨蝶呤化疗后为患儿增加口腔护理,能有效预防口腔溃疡,减轻患儿病情严重程度,改善患儿心理状态,提升患儿进食量和生活质量,缩短愈合时间,具有推广价值。

Combination of Diclofenac Potassium and Propolis in the Therapy of Oral Aphthosis: A Randomized, Clinical, Double-Blind, Placebo-Controlled Study

Background: Oral aphthosis has a negative impact on oral health. This study aimed to assess the effectiveness of gel formulation including diclofenac and propolis in the treatment of oral ulcers. Methods: Participants included 100 normal individuals with aphthous, excluding those having allergies to any ingredient in the diclofenac formulation. Patients were randomly assigned into two groups: one group received treatment with a combination of diclofenac potassium 3% (10 mg/g, 60 g) and propolis 5% gel (Group II), and the other group received a placebo (Group 1). The patient was evaluated using standard digital photographs and chronic oral mucosal questionnaires on days 1, 3, 5, and 7 after healing. Utilizing the Mann-Whitney U test, the two groups were compared. Each group’s changes were examined using Friedman’s test. Results: There was a statistically dramatic change over time in Group II. After one day, the median total score dropped statistically significantly, and from one to three days with effect size (d) 2.485, Group II demonstrated 48% complete healing and 52% partial healing, while Group I demonstrated 4% partial healing and 96% no change. Effect size (V): 0.995. Conclusions: The combination of diclofenac and propolis provided instant relief and an affordable new regimen for treating oral aphthosis.

芡实壳提取物的抗氧化活性及对口腔溃疡模型大鼠的治疗作用

目的研究芡实壳对口腔溃疡模型大鼠的防治作用及其潜在作用机制。方法分别以福林酚法、硝酸铝比色法测定芡实壳-萃取物中多酚、黄酮含量;以DPPH·、ABTS^(+)·、·OH和·O_(2)4种自由基清除实验评价体外抗氧化活性;冰醋酸灼伤法建立口腔溃疡大鼠模型。采用酶联免疫法检测血清中氧化因子水平;HE染色观察溃疡黏膜组织病理变化;Western blot方法检测溃疡黏膜组织中Keap1、Nrf2、Nes-Nrf2和HO-1蛋白表达水平。结果乙酸乙酯萃取物中多酚、黄酮含量为306.74±1.04 mg/g、23.43±0.61 mg/g,其清除DPPH·、ABTS^(+)·自由基的IC50分别是3.42±0.97µg/mL、3.32±0.90µg/mL(P<0.01);乙酸乙酯组能明显改善模型动物口腔黏膜损伤,提高血清中CAT水平、降低MDA水平(P<0.01),显著增加血清中NEs-Nrf2(P<0.01)以及HO-1(P<0.05)蛋白表达量、降低Keap1(P<0.01)蛋白表达量显著。结论芡实壳提取物对口腔溃疡有一定治疗作用,其作用机制可能是通过激活Keap1/Nrf2/HO-1信号通路。

腭部坏死性唾液腺化生1例

坏死性唾液腺化生是一种罕见的、具有自限性的疾病,主要累及唾液腺及周围组织。该病临床及病理表现易与其他疾病,尤其是与恶性肿瘤相混淆,因此掌握坏死性唾液腺化生的相关知识对于正确诊断和治疗,避免误诊及过度治疗具有重要意义。本文报告1例表现为腭部深大溃疡的坏死性唾液腺化生病例的诊疗过程,以期为临床诊疗提供参考。

以口腔黏膜溃疡为首发表现的结外鼻型NK/T细胞淋巴瘤的多学科诊疗1例

结外鼻型NK/T细胞淋巴瘤(extranodal nasal type NK/T-cell lymphoma,ENKTL)是一种以破坏面部中份结构为主的NK/T细胞来源的非霍奇金淋巴瘤,临床少见。以口腔黏膜溃疡为首发症状的病例罕见且易与其他疾病相混淆,在诊断上极其困难。本文报道1例以颊黏膜及牙龈溃疡为首发表现的ENKTL的多学科诊疗,并分析该疾病的临床病理学特征、诊断、鉴别诊断和治疗,以期为临床诊治相关病例提供参考。

基于“三焦分消”理念分析三仁汤“异病同治”治疗溃疡性疾病的临证思路

溃疡性疾病是临床中的常见病、多发病,亦是中医优势病种之一。异病同治是中医辨证论治的精髓,其核心是“证同则治同,证异则治异”,若不同的疾病在发展过程中,出现了相同的病机与证候,即可采用同一方法进行治疗。三仁汤是治疗温病湿热证的代表方剂,可通过宣上、畅中、渗下将湿热之邪由三焦分消走泄而去。溃疡性疾病包括口腔溃疡、胃溃疡、溃疡性结肠炎等病,临证之际,“有是证用是方”,若疾病证属湿热蕴结,投以三仁汤治之,疗效颇佳。从疾病“异病同治”的角度出发,基于“三焦分消”理论初步探讨三仁汤在溃疡性疾病中的临床运用,以期为溃疡性疾病的临床治疗提供参考。

口腔溃疡与乳腺癌风险的孟德尔随机化研究

目的根据双向两样本孟德尔随机化(Mendelian randomization,MR)方法,探讨口腔溃疡与乳腺癌之间的因果关系。方法利用大规模遗传数据集,进行双向MR分析,使用暴露数据集和结果数据集推断因果关系。确定与口腔溃疡相关的遗传工具变量,并检查其与乳腺癌的关联。为确保因果关系推断的稳健性,使用孟德尔随机化Egger(MR egger)法、逆方差加权法(inverse variance weighted,IVW)、加权中位数法(weighted median,WM)、简单模式和加权模式等多种MR方法。此外,进行异质性和多向性检验,来评估MR结果的可靠性。结果MR显示,当口腔溃疡被视为暴露因素时,口腔溃疡与乳腺癌之间存在负相关(OR 0.396;95%CI 0.175至0.897;P<0.05)。在逆向MR中未观察到支持乳腺癌对口腔溃疡产生影响的显著结果(所有P>0.05)。结论通过MR方法证明口腔溃疡可能是乳腺癌的保护因素,在探究口腔溃疡与乳腺癌关系时需要综合多种研究方法。