Pedunculoside promotes oral ulcer healing in mice by upregulating STAT3 and Smad3

Background:Pedunculoside(PE)is a pentacyclic triterpenoid saponin found in the dried barks of the Ilex rotunda Thunb.In traditional Chinese medicine,the juice extracted from various Ilex species is commonly used for treating inflammatory diseases.Objective:This study aims to investigate the potential of PE in promoting the healing of oral ulcers in mice and to explore its possible mechanism.Materials and Methods:A mouse model of oral ulcer was established to evaluate the healing promotion effects of PE,and an in-vitro inflammatory cell model was established by using primary fibroblasts isolated from mouse oral mucosal tissue.Gene transcription and protein expression related to cell proliferation,migration,and collagen synthesis were measured.Results:PE showed the highest cure rate of 85.7%for oral ulcers in mice within 7-days treatment.It significantly promoted cell proliferation and collagen secretion in fibroblast in-vitro model.PE also upregulated the gene transcription of Smad3,Col1a1 and Col3a1.Furthermore,PE antagonized the inhibitory effect of WP1066 on STAT3activation,but did not affect cell migration.Conclusion:This study demonstrates that PE has potential therapeutic effects in promoting oral ulcer healing in mice.The improvement was achieved by the increasing collagen synthesis through the upregulation of STAT3 and Smad3 in mucosa fibroblasts.These results provide a preliminary pharmacological work for developing PE as a potential treatment agent for oral ulcers.

Therapeutic and recurrence-preventing effects of Qi-Replenishing and Blood-Activating Formula in rats with acetic acid-induced gastric ulcer

Objective:To explore the therapeutic and recurrence-preventing effects of Qi-Replenishing and Blood-Activating Formula in rats with acetic acid-induced gastric ulcer.Methods:A total of 138 SD rats were selected to make rat models with gastric ulcer induced by acetic acid(24 rats with sham operation served as sham operation group),and were randomly divided into model group(n=30),western medicine group(n=30),traditional Chinese medicine(TCM) group(n=24) and combination group(combined western medicine and TCM group,n=30).Western medicine group was gavaged with omeprazole in the morning and with iso-volumetric distilled water in the afternoon;TCM group and TCM sham operation group were gavaged with iso-volumetric distilled water in the morning and with Qi-Replenishing and Blood-Activating Formula in the afternoon;combination group was gavaged with omeprazole in the morning and with Qi-Replenishing and Blood-Activating Formula in the afternoon;sham operation group and model group were gavaged with iso-volumetric distilled water both in the morning and afternoon.Ulcer indexes and degree of mucosal degree in rats at different time points after gavage were observed.Twentyeight days after gavage,interleukin(IL)-1β was given to induce ulcer recurrence so as to observe the recurrent severity and rate of ulcer in each group.Results:Compared with model group and western medicine group,treatment in combination group could prominently reduce the ulcer index of rats with peptic ulcer,and increase the healing rate and inhibition rate of peptic ulcer.After IL-1β-induced ulcer recurrence,combination group was significantly superior to model group and western medicine group in ulcer recurrent rate[50%(3/6) vs.100%(6/6)]and severity.Conclusions:Basic acid-suppression therapy combined with Qi-Replenishing and BloodActivating Formula can effectually improve the ulcer healing quality and reduce ulcer recurrence.

Short term effect of Salvia miltiorrhiza in treating rat acetic acid chronic gastric ulcer and long term effect in preventing recurrence

AIM To study the short term effect of Danshen ( Salvia miltiorrhiza ) on acetic acid induced chronic gastric ulcer in rats and its long term effect in preventing recurrence. METHODS Rats with acetic acid induced gastric ulcer were treated with Danshen and cimetidine for 30 days. Traditional gastric mucosal auto radiography and 3H TdR incorporation into gastric mucosa in vitro were employed to study the effects of Danshen in rat acetic acid induced chronic gastric ulcer, including ulcer index (UI), ulcer inhibitory rate (IR) and label rate (LR). RESULTS On the day 5, 30 and 126 of ulcer making, the UI in the Danshen group was obviously lower than that in the cimetidine group and the control group (42 3±3 9, 3 6±1 2, 4 4±2 3; 49 1±3 6, 5 9±1 4, 9 2±1 3; 61 0±3 8, 8 9±2 5, 12 4±2 4, respectively, P <0 01), the IR (%) in the Danshen group was obviously higher than that in the cimetidine group (31, 59, 64 8; 19, 33, 26, respectively), and the LR in the Danshen group was obviously higher than that in the cimetidine group and the control group (10 0±0 5, 16 2±0 8, 15 0±0 6; 9 0±0 5, 13 9±0 6, 10 8±0 7; 6 5±0 7, 10 1±0 5, 8 0±0 7, respectively, P <0 01). There was no obvious difference in UI in the Danshen group on day 30 as compared with that on day 126. CONCLUSION Danshen is effective in promoting ulcer healing and preventing recurrence. The mechanism of action is to strengthen the gastric mucosal barrier and to promote the gastric mucosal cell proliferation along the edge of the ulcer.

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.

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.

Mechanism and Research Progress of Fuyang Huoxue Jiedu Formula against Recurrence of Ulcerative Colitis

By introducing the composition and modern pharmacology of Fuyang Huoxue Jiedu Formula,the paper further explored the mechanism and research progress of Fuyang Huoxue Jiedu Formula against recurrence of ulcerative colitis(UC).The formula can effectively improve the TCM syndromes of UC patients,reduce the recurrence rate,and improve clinical efficacy and patients’quality of life.

The recurrence and survival of oral squamous cell carcinoma: a report of 275 cases

Oral squamous cell carcinoma(OSCC) is a common malignant tumor of the head and neck, and recurrence is an important prognostic factor in patients with OSCC. We explored the factors associated with recurrence of OSCC and analyzed the survival of patients after recurrence. Clinicopathologic and follow-up data of 275 patients with OSCC treated by surgery in the Cancer Institute and Hospital of Tianjin Medical University between 2002 and 2006 were analyzed. Recurrence factors were analyzed with Chisquare or Fisher′s exact test and multivariate analysis. The prognosis of patients after recurrence was analyzed with the Kaplan-Meier method and log-rank test. The recurrence rate was 32.7%. The recurrence time ranged from 2 to 96 months, with a median of 14 months. Univariate analysis showed that T stage, degree of differentiation, pN stage, flap application, resection margin, and lymphovascular invasion were factors of recurrence (P<0.05). Multivariate analysis showed that T stage, degree of differentiation, and pN stage were independent factors of recurrence (P<0.001). The differences in gender, age, tumor site, region of lymph node metastasis, and perineural invasion between the recurrence and non-recurrence groups were not significant (P>0.05). Kaplan-Meier and log-rank tests showed that the 2- and 5-year survival rates were significantly lower in the recurrence group than in non-recurrence group(67.6% vs. 88.0%, 31.8% vs. 79.9%, P<0.001). Therefore, to improve prognosis, we recommend extended local excision, flap, radical neck dissection, and adjuvant chemoradiotherapy for patients more likely to undergo recurrence.

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.

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.

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.

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.

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.

Multivariate analysis of oral mucosal ulcers during orthodontic treatment

BACKGROUND Orthodontic treatment can easily cause local soft tissue reactions in the oral cavity of patients under mechanical stress,leading to oral mucosal ulcers and affecting their quality of life.At present,only limited literature has explored the factors leading to oral ulcers in orthodontic treatment,and these research results are still controversial.AIM To investigate the current status and related factors of oral mucosal ulcers during orthodontic treatment,aiming to provide a valuable reference for preventing this disease in clinical practice.METHODS A total of 587 patients who underwent orthodontic treatment at the Peking University School of Stomatology and Hospital of Stomatology between 2020 and 2022 were selected and allocated to an observation or control group according to the incidence of oral mucosal ulcers during orthodontic therapy.A questionnaire survey was constructed to collect patient data,including basic information,lifestyle and eating habits,treatment details,mental factors,and trace element levels,and a comparative analysis of this data was performed between the two groups.RESULTS A logistic regression model with oral ulcers as the dependent variable was established.The regression results showed that age(≥60 years:odds ratio[OR]:6.820;95%confidence interval[CI]:2.226–20.893),smoking history(smoking:OR:4.434;95%CI:2.527–7.782),toothbrush hardness(hard:OR:2.804;95%CI:1.746–4.505),dietary temperature(hot diet:OR:1.399;95%CI:1.220–1.722),treatment course(>1 year:OR:3.830;95%CI:2.203–6.659),and tooth brushing frequency(>1 time per day:OR:0.228;95%CI:0.138–0.377)were independent factors for oral mucosal ulcers(P<0.05).Furthermore,Zn level(OR:0.945;95%CI:0.927–0.964)was a protective factor against oral ulcers,while the SAS(OR:1.284;95%CI:1.197–1.378)and SDS(OR:1.322;95%CI:1.231–1.419)scores were risk factors.CONCLUSION Age≥60 years,smoking history,hard toothbrush,hot diet,treatment course for>1 year,tooth brushing frequency of≤1 time per day,and mental anxiety are independent risk factors for oral mucosal ulcers.Therefore,these factors should receive clinical attention and be incorporated into the development and optimization of preventive strategies for reducing oral ulcer incidence.

A cuttlefish ink nanoparticle-reinforced biopolymer hydrogel with robust adhesive and immunomodulatory features for treating oral ulcers in diabetes

Oral ulcers can be managed using a variety of biomaterials that deliver drugs or cytokines.However,many patients experience minimal benefits from certain medical treatments because of poor compliance,short retention times in the oral cavity,and inadequate drug efficacy.Herein,we present a novel hydrogel patch(SCE2)composed of a biopolymer matrix(featuring ultraviolet-triggered adhesion properties)loaded with cuttlefish ink nanoparticles(possessing pro-healing functions).Applying a straightforward local method initiates the formation of a hydrogel barrier that adheres to mucosal injuries under the influence of ultraviolet light.SCE2 then demonstrates exceptional capabilities for near-infrared photothermal sterilization and neutralization of reactive oxygen species.These properties contribute to the elimination of bacteria and the management of the oxidation process,thus accelerating the healing phase’s progression from inflammation to proliferation.In studies involving diabetic rats with oral ulcers,the SCE2 adhesive patch significantly quickens recovery by altering the inflamed state of the injured area,facilitating rapid re-epithelialization,and fostering angiogenesis.In conclusion,this light-sensitive hydrogel patch offers a promising path to expedited wound healing,potentially transforming treatment strategies for clinical oral ulcers.

Enhancing ulcerative colitis treatment with traditional Chinese medicine

Inflammatory bowel disease,particularly ulcerative colitis(UC),poses significant treatment challenges due to its chronic nature and potential for severe complications.This editorial reviews a recent network meta-analysis that evaluated the efficacy of and highlighted the superior outcomes achieved by combining each of five traditional Chinese medicine(TCM)formulations with mesalazine for the adjuvant treatment of UC.Clinical outcomes included enhanced mucosal healing,improved quality of life,and reduced recurrence rates.Additionally,the combination therapy resulted in a lower incidence of adverse reactions compared with mesalazine monotherapy.Despite these promising results,limitations such as variability in study quality and TCM dosage highlight the need for further highquality,large-sample,multicenter randomized controlled trials.This editorial underscores the potential of TCM in enhancing UC management and calls for more rigorous research to substantiate these findings and refine clinical guidelines.

Analysis of correlative factors in peptic ulcer recurrence in the elderly

Objective To analyze the correlative factors of peptic ulcer recurrence in the elderly.Methods From January to December 2009,169 elderly patients(≥60 years old)with peptic ulcer delected by edoscopy were enrolled,whose treatment and usage of medication were analyzed.Data of treatment and recurrence in 3-year follow-up were recorded.Mann-Whitney rank sum test

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.

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 without high-risk stigmata.METHODS： This randomized study included 211 patients [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 fiat 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 reevaluated 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 bleeding 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.

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.