Evaluation of a Newly Developed Laser Pen as a Home Care Device for Pain Reduction of Recurrent Aphthous Stomatitis (Preliminary Study)

Objective: The aim of this survey is to evaluate the effect of a new developed laser pen as a home care device for patients’ pain reduction with recurrent aphthous stomatitis. Background data: Recurrent aphthous stomatitis (RAS) is one of the most common and painful ulcers in the oral cavity. Low Level Laser Therapy (LLLT) has been used successfully for reducing pain and healing time in comparison with corticosteroids and placebo in some studies. But these treatments are done in the clinics and it seems that there is no report of the laser treatment as a home care device up to this study. Methods: This was a prospective, randomized trial pilot study. Thirty patients with RAS were divided into three similar groups. The group one (n = 10) was treated with a diode laser, 660 nm, 40 mw, continuous wave, 1.2 J, 6 J/cm2, for five consecutive days (twice per day, 30 seconds each session). The second group (n = 10) was treated with a topical triamcinolone (adcortyl in orabase) ointment four times per day and the third group (n = 10) was treated with placebo (red light pen) the same way as Group 1. All the patients were evaluated with a Visual Analogue Scale (VAS) before and after treatment on the consecutive days. The data was analysed by one way ANOVA and PostHoc tests. Results: The results show that the laser pen and triamcinolon in orabase ointment have similar results and both have better results than placebo in the control of the recurrent aphthous stomatitis pain (p value: 0.001). Conclusion: In this clinical pilot study the laser pen as a home care device seems to be useful for the treatment of RAS.

The Local Immunity of the Oral Cavity in Women with Recurrent Aphthous Stomatitis Associated with Urogenital Infection

This paper studied the dynamics of local immunity factors of the oral cavity in women with recurrent aphthous stomatitis against the background of urogenital infection. The research proves the maximum efficacy of hydroxyzine hydrochloride, aminodihydrophthalasindione sodium and Eplan used in multiple treatments of recurrent aphthous stomatitis in patients with urogenital infection as evidenced by a marked reduction in the coefficient of local immunity factors balance, which is observed as early as on day 7 of the therapy provided. Moreover, the findings show the growth of immunological parameters of oral fluid (lysozyme and SIgA), the normalization of the coefficient of local immunity factors balance in the treatment of recurrent aphthous stomatitis in women with urogenital infection, the improvement being observed 3 months after the treatment suggesting a favorable local immunity of the oral cavity.

Treatment of Recurrent Aphthous Stomatitis by 100% Topical Pumpkin Seed Oil

Background: Recurrent aphthous stomatitis (RAS) is a major oral health problem, where its etiopathogenesis is not well understood. Accordingly, its therapy whether topical or systemic can induce clearance, but the relapse rate is high. Objective: To use 100% topical pumpkin seed oil in RAS as it has many actions as anti-inflammatory and antioxidant effects. Patients and Methods: This single, blind, clinical, therapeutic trial was conducted in the Department of Dermatology-Baghdad Teaching Hospital, Baghdad, Iraq, during February 2015-August 2016. Twenty-five patients with RAS were included in this work. After full history and clinical examination, the clinical diagnosis was established. Oral clinical manifestation index score (OCMI) was carried out before, during and after stopping therapy to assess the different parameters of this score. 100% Topical pumpkin seed oil was given two times daily for 3 months during which short term assessment for each patient was done by using OCMI before, after 4 days and after 8 days of therapy in addition to assessing the mean size of largest diameter of ulcers in each visit to evaluate the therapeutic efficacy of the therapy, while long term assessment of the OCMI was done every month for 3 months after starting of the therapy to evaluate the prophylactic effect of the therapy. After 3 months, pumpkin seed oil was stopped and assessment of OCMI was done monthly for another 3 months to evaluate the remission action of pumpkin seed oil. Results: Twenty-five patients were included in this study: 15 (60%) males and 10 (40%) females. While their ages ranged from 9 - 60 (27.48 ± 11.97) years. The mean of OCMI before pumpkin seed oil therapy was ranged from 9 - 15 (12.96 ± 1.42), while after the therapy the mean started to decline to lower level within 4 days of therapy and was statistically significant (p < 0.0001) and continued to decline significantly till the end of third month of therapy (p < 0.0001). The percent reduction was 79.30% after 4 days of therapy and 94.38% after 8 days of therapy. After stopping therapy, the mean of OCMI started to increase, but it is remained statistically highly significant (p < 0.0001) at the end of third months after stopping therapy when it is compared with baseline mean of OCMI. Conclusion: Pumpkin seed oil had an effective therapeutic and prophylactic action against RAS, in addition, it induced remission for at least 3 months after stopping therapy. No local or systemic side effects were observed during the course of therapy.

Therapeutic Role of Isotretinoin in the Management of Recurrent Aphthous Stomatitis (Single-Blind Controlled Therapeutic Study)

Background: Recurrent aphthous ulcer (RAS) is a common oral disease where its etiopathogenesis is not well elucidated. There was no effective curative therapy for this disease. Isotretinoin has been recently used in the treatment of Behcet’s disease. Objectives: To evaluate the efficacy and safety of isotretinoin in treating RAS and the long term remission of RAS. Patients and Methods: This single-blind controlled therapeutic study conducted in Department of Dermatology-Baghdad Teaching Hospital during February 2011-January 2012. Thirty patients with typical RAS were included in this work. Detailed history and full examination were done for all patients. They were given isotretinoin 20 mg orally once daily for three months to be seen on Day 14 firstly and then monthly to be assessed using the oral clinical manifestation index (OCMI). After isotretinoin was stopped three months later, patients were given placebo therapy for another 3 months. Results: The results of 30 treated patients were as follows: 17 (56.67%) males and 13 (43.33%) females with male to female ratio was 1.3:1. Their ages ranged from 12 - 60 (35.33 ± 12.06) years. The OCMI before isotretinoin therapy ranged from 7 - 17 (13.13 ± 2.55), while after therapy the mean started to decline to a lower level within the first 14 days (P = 0.103), and continued to decline significantly until the end of the first month of therapy (P = 0.023). Then the OCMI declined very significantly until the end of fourth month of therapy (P < 0.001). After that the mean started to increase until the end of the 5 months (with placebo) but it remained statistically significant compared with the baseline of mean of OCMI before treatment (P = 0.046). Then it continued to increase to become not significant at the end of 6 months of therapy (P = 0.107). Conclusion: Isotretinoin is an effective therapeutic and prophylactic promising remedy in treatment of RAS.

Effects of Zingiber officinalis (WILLD.)ROSC.Membranes on minor recurrent aphthous stomatitis: a randomized pragmatic trial

Objective:To evaluate the effects of dried ginger rhizome (DGR;Zingiber officinalis (WILLD.) ROSC.),prepared as a membrane,in minor recurrent aphthous stomatitis (miRAS)treatment and explore its mechanism of action by detecting changes in levels of epidermal growth factor (EGF) and tumor necrosis factor (TNF)-α in saliva.Methods:Fifty-nine miRAS patients were enrolled in this study.The number of participants in the dried ginger rhizome membrane (DGRM) group was 30,and 29 were in the placebo membrane (PM) group.Sixty sealed envelopes containing either type of membrane were coded randomly.Investigators and participants were blinded to group assignments.A visual analog scale (VAS) was used for pain,follow-up information for healing time,and enzyme-linked immunosorbent assays to measure the concentrations of EGF and TNF-α.Results:In terms of VAS,there was a significant difference between pre-and post-DGRM treatment (P <.001),but not so for the PM group (P >.05).A significant difference was observed in the healing time between the two groups (6.08 (2.712) vs.8.04 (2.142) days).The mean healing time in the DGRM group was shorter than that in the PM group (P <.05).In both groups,the salivary EGF concentration decreased significantly after treatment (P <.05),but the mean level in the DGRM group was significantly lower than that in the PM group (P <.05).The mean TNF-α level in both groups was increased significantly after treatment (P <.05),but patients who used DGRMs had a significantly lower level than that in the PM group (P <.05).Conclusion:The present study provides evidence that DGRMs are effective treatment for RAS.Dried ginger rhizome has obvious effects on pain relief,shortening of healing time,reducing the EGF level in saliva,and has an inhibitory effect on TNF-α release.

Successful Treatment of PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis) Syndrome with Shinbuto

Periodic fever with aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is an autoimmune disorder and the most common disorder characterized by periodic fever in children. A male patient has been followed up from 11 months to 10 years of age because of repeated high fever. We prescribed antifebriles and antibiotics for each febrile episode without a beneficial effect to him each time. He required several days of rest at home to recover from each episode. During his most recent febrile episode at 10 years of age, we prescribed 5.0 g of shinbuto (TJ-30;Tsumura Co., Tokyo, Japan). His fever resolved the next day and he was able to attend school. His growth and development are normal. Shinbuto had a therapeutic effect in this patient with PFAPA syndrome and may be useful in this condition.

Diagnosis and Control of Swine Vesicular Stomatitis

Swine vesicular stomatitis is an acute, febrile, highly contagious zoonotic diseases caused by vesicular stomatitis virus （VSV）. Disease in affected pigs was typically characterized by vesicular lesions on the mouth, snout, oral mucosa, coronet and interdigital skin. The disease is endemic in the Americas, Europe and Africa and other places. As the foreign trade of animals and animal products increase, the risk of swine vesicular stomatitis spreading into our country also will be increased. Therefore, the accurate and timely diagnosis and control of swine vesicular stomatitis are critical and necessary.

Necrotising stomatitis as a presenting symptom of HIV

Background: Necrotising Stomatitis is an uncommon oral infection associated with diminished systemic resistance (immunocompromised state) including HIV infection. Significant predisposing factors include poor oral hygiene, unusual life stress, recent illness (e.g. Measles), malnutrition, smoking and even inade- quate sleep. It occurs commonly in developing na-tions with poor living conditions. Objective: To present a case of severe Necrotising Stomatitis in a previously undiagnosed HIV Seropositive patient. Patient and method: This case report describes severe, rapidly spreading necrotising stomatitis in a 35 years old lady, the condition which led to her being diagnosed with HIV. The treatment modalities, challenges of man-agement and the differential diagnosis were discussed. Result: During the course of her management, pa-tient’s oral condition improved. However, later re-currence was seen due to severe anaemia caused by malnutrition and aggravated by Zidovudine antiret-roviral drug. Conclusions: There is need for interdis-ciplinary interactions between the dentists and the physicians managing HIV patients, to allow effective management and afford patient the best treatment.

Salivary cytokines and levels in denture stomatitis: An exploratory case-control study

We aimed to evaluate the microbial and inflammatory characteristics associated with Denture Stomatitis (DS) analyzing: l) Levels of salivary cytokines and cultivable C. albicans;2) DNA-DNA checkerboard on biofilm associated with mucosal tissue-bearing denture surfaces, 3) Serum C-reactive protein (CRP) levels. Thirty-two subjects were enrolled in the study with control (n = 17) and DS types II and III (n = 15) subjects. Samples were collected from unstimulated whole saliva, serum and swabs from denture surfaces. Salivary levels of inflammatory mediators and CRP were measured by multiplex. Samples from denture and mucosal surfaces were analyzed by DNA-DNA checkerboard. Saliva from DS subjects showed increase in IL-8 (p = 0.04) and IL-1β (p = 0.04) with trend for increase in IL-1β, TNFα and IL-6 levels. C. albicans higher counts in DS saliva (p = 0.03) showed association with elevated levels of IL-8 (p = 0.03) and IL-1α (p = 0.01). CRP levels were not different among groups (p = 0.74). DNA-DNA checkerboard analyses indicated typical periodontal pathogens below the detection threshold of 104 organisms on both denture and inflamed mucosal surfaces. The data suggest that DS is associated with elevation of salivary IL1 and IL-8 together with increased C. albicans. There was no evidence of systemic inflammation as measured by serum C-reactive protein levels.

Clinical Study on External Use of Chinese Medicine in Treating Children with Herpetic Stomatitis

Background: Pediatric herpetic stomatitis is a common pediatric disease, the course of the disease is about 1 - 2 weeks, and it usually occurs in 1 - 3 years old children, due to infection of herpes simplex virus I and onset. Objective: To observe the curative effect of Chinese medicine prescription (Yueshi, Zhongbai, Qingdai, Phelloderma phelloderma and glycyrrhiza) on children with herpetic stomatitis. Methods: 90 patients were divided into 2 groups by random number table method. 45 patients in the observation group were treated with traditional Chinese medicine, and 45 patients in the control group were treated with iodine glycerin. The total effective rate after treatment was compared between the two groups. Results: The total effective rate of the treatment group was 95.55%;the total effective rate of the control group was 71.11%;the total effective rate of the two groups after treatment was compared;the treatment group was significantly better than the control group;the difference was significant (P 0.05). Conclusion: The external use of Chinese medicine in the treatment of pediatric herpetic stomatitis has achieved good results, improving the condition of children, and significantly improving the clinical efficacy.

Adverse Effects of Morphine and Fentanyl for Stomatitis in Patients Receiving Allogeneic Hematopoietic Cell Transplantation—A Single Center Retrospective Analysis

Opioids are widely used as analgesics for oral mucositis in allogeneic hematopoietic cell transplantation (allo-HCT). Their main adverse events are nausea, vomiting, constipation, psychological symptoms, and respiratory depression. In our institute, continuous intravenous morphine was generally used until 2007, followed by intravenous fentanyl as the first-line agent because of its potential fewer adverse events. We retrospectively analyzed 99 patients who underwent allo-HCT in the University of Tsukuba Hospital from 2004 to 2009. Out of 99 patients, 64 were treated with opioids (morphine, 32 and fentanyl, 32). The attending physicians were in charge of providing stable pain control. Median age, sex, stem cell source, preparative regimen, and GVHD prophylaxis were similar in the two groups. There were no significant differences in psychological symptoms, drowsiness, nausea, and vomiting in both groups. Defecation ratio (the days having a bowel movement/the days taking opioids) was 63% and 94% in the morphine and fentanyl group, respectively (P < 0.0001). The percentage of patients who needed to use purgative drugs was 25% and 6% in the morphine and fentanyl group, respectively (P = 0.04). It is suggested that fentanyl has less adverse effects on gastrointestinal movement and is safer than morphine when used for oral mucositis in allo-HCT.

A comparison of the effects of Kangfuxin liquid and watermelon frost spray for recurrent aphthous stomatitis:A meta-analysis

Through a meta-analysis,we comprehensively evaluated the clinical efficacy and safety of Kangfuxin liquid(KFXL)in patients with recurrent aphthous stomatitis(RAS).Randomized controlled clinical trials(RCTs)involving RAS patients treated with KFXL were systematically retrieved from several online databases from inception to December 2021.All the study selection,data extraction,and quality assessments were performed by two independent investigators using the Cochrane systematic review method.The total effective rate,VAS pain score,recurrence rate,and ulcer healing time were analyzed using Rev Man 5.3 software and Stata 16.0.A total of 17 studies consisting of 1703 patients were included in our investigation.The pooled result indicated that when compared with watermelon frost spray(WFS),KFXL had a significantly superior clinical effectiveness rate(logRR=0.19,95%CI:0.15 to 0.22,P<0.00001).Moreover,the ulcer healing time(MD=–1.63,95%CI=–2.32 to–0.93,P<0.00001),VAS pain score(MD=–1.81,95%CI:–2.65 to–0.97,P=0.00),and recurrence rate(logRR=–0.65,95%CI=–0.89 to 0.42,P<0.00001)of patients with RAS were also significantly improved after receiving the KFXL therapy.Our study revealed that KFXL was a more effective treatment for RAS than WFS,and it could significantly decrease the VAS pain score,recurrence rate,and ulcer healing time in patients.However,our study was limited by the quality of available literature,and further robust trials are needed for a more accurate analysis.

Identification and Functional Analysis of Serum Specific miRNAs in Recurrent Aphthous Stomatitis Patients with Excess-heat or Yin-deficiency

Background:The treatment of Traditional Chinese Medicine(TCM)in recurrent aphthous stomatitis(RAS)based on syndrome differentiation has won the international acceptance,but the molecular mechanism of excess-heat syndrome and yin-deficiency syndrome of RAS remains unclear.Objective:To clarify specific microRNAs(miRNAs)and their functions in RAS patients with excess-heat or yin-deficiency.Methods:Serum samples were collected from patients meeting the RAS diagnostic criteria of excess-heat or yin-deficiency syndrome and healthy individuals.Core miRNAs were then identified under miRNA microarray anal-yses.Target prediction and bioinformatic analyses were carried out and gene-pathway-networks were visualized to better understand the relationship between different genes and pathways.Results:(1)90 individuals meeting the inclusion criteria were collected in this study.Among them,9 miRNAs were screened out in excess-heat syndrome group(EH group),with 1 upregulated and 8 downregulated.And four miRNAs(hsa-miR-20b-5p,hsa-miR-122-5p,hsa-miR-483-5p and hsa-miR-3197)were validated by real-time PCR method.14 miRNAs were screened out in yin-deficiency syndrome group(YD group)(7 upregulated and 7 downregulated).And hsa-miR-17-5p,hsa-miR-106-5p and hsa-miR-20b-5p were validated.(2)A total of 4,776 target genes were identified in EH group which enriched in GO categories including nervous system development and calcium ion binding and pathway such as PI3K-Akt signaling pathway and Calcium signaling pathway.10,172 target genes were identified in YD group which enriched GO categories included protein binding and positive regulation of transcription from RNA polymerase II promoter and pathway included MAPK signaling pathway and Ras signaling pathway.Conclusion:Hsa-miR-20b-5p in patients with RAS could act as the novel target for the classification of the syndrome.It is upregulated in RAS patients with excess-heat syndrome while downregulated in patients with yin-deficiency syndrome.The PI3K-Akt and MAPK signaling pathways and their related target genes may provide new insights into the molecular mechanisms of RAS with excess-heat syndrome or yin-deficiency syndrome,respectively.

A novel vesicular stomatitis virus armed with IL-2 mimic for oncolytic therapy

Oncolytic virus(OV)is increasingly being recognized as a novel vector in cancer immunotherapy.Increasing evidence suggests that OV has the ability to change the immune status of tumor microenvironment,so called transformation of‘cold’tumors into‘hot’tumors.The improved anti-tumor immunity can be induced by OV and further enhanced through the combination of various immunomodulators.The Neo-2/15 is a newly de novo synthesized cytokine that functions as both IL-2 and IL-15.However,it specifically lacks the binding site of IL-2 receptorαsubunit(CD25),therefore unable to induce the Treg proliferation.In present study,a recombinant vesicular stomatitis virus expressing the Neo-2/15(VSVM51R-Neo-2/15)was generated.Intratumoral delivery of VSVM51R-Neo-2/15 efficiently inhibited tumor growth in mice without causing the IL-2-related toxicity previously observed in clinic.Moreover,treatment with VSVM51R-Neo-2/15 increased the number of activated CD8t T cells but not Treg cells in tumors.More tumor-bearing mice were survival with VSVM51R-Neo-2/15 treatment,and the surviving mice displayed enhanced protection against tumor cell rechallenge due to the induced anti-tumor immunity.In addition,combination therapy of OV and anti-PD-L1 immune checkpoint inhibitors further enhanced the anti-tumor immune response.These findings suggest that our novel VSVM51R-Neo-2/15 can effectively inhibit the tumor growth and enhance the sensitivity to immune checkpoint inhibitors,providing promising attempts for further clinical trials.

A Vesicular Stomatitis Virus-Based Vaccine Carrying Zika Virus Capsid Protein Protects Mice from Viral Infection

Dear Editor,Zika virus (ZIKV) is a mosquito-borne virus that belongs to the Flavivirus family along with dengue virus (DENV),yellow fever virus, West Nile virus, and Japanese encephalitis virus (Ming et al. 2016). ZIKV is a singlestranded positive-sense RNA virus encoding three structural proteins, including nucleocapsid protein C, prM/M,envelope glycoprotein E, and seven non-structural proteins.Since 2015.

Therapeutic Evaluation of Recurrent Aphthous Ulcer with Integrated Traditional Chinese Medicine and Western Medicine

Objective: To observe the curative effects of Yiqing granule and Zhibai Dihuang pill combined with Oralpolin gel on recurrent aphthous ulcer. Methods: 150 patients with mild recurrent aphthous ulcer were classified as excessive internal heat type and deficiency internal heat type by traditional Chinese medicine theory. Then, they were randomly divided into the positive control group (thalidomide group), the trial group (Yiqing granule group/Zhibai Dihuang pill group), and the negative control group (topical medication group). All the patients in every group used Oralpolin gel. Additionally, the patients in the positive control group took thalidomide tablets orally and those in the trial group orally took proprietary Chinese medicine (Yiqing granule/Zhibai Dihuang pill). The treatment lasted for 4 weeks. The curative effects were all evaluated according to the “RAU Efficacy Evaluation Trial Standard” which was formulated by the Professional Committee of Mucosal Diseases of Chinese Stomatological Association. Results: Of all the 150 patients involved in this medical experiment, 146 cases finished it, including 66 ones in the trial group, 36 ones in the positive control group, and 44 ones in the negative control group. The total drop-out rate was 2.7%. For the excessive internal heat type, the effective rates in the thalidomide group, the Yiqing granule group and the local medication group were 91.7%, 52.6% and 52.9% respectively in order. For the deficiency internal heat type, the effective rates in the thalidomide group, the Zhibai Dihuang pill group and the local medication group were 87.5%, 71.4% and 40% respectively in order. The clinical efficacy of the Zhibai Dihuang pill group was better than that of the local medication group and similar to that of the thalidomide group (P Conclusion: Zhibai Dihuang pill is significantly effective in the treatment for mild recurrent aphthous ulcer of deficiency internal heat type without severe adverse reactions.

RADIOIMMUNOASSAY OF SERUM FERRITIN LEVEL IN PATIENTS WITH RECURRENT APHTHOUS ULCERATION

The purpose of this study was to assess the correlation between iron deficiency and recurrent aphthous ulceration (RAU). Radioimmunoassay was used to examine the serum ferritin level (SFL) in 52 patients with RAU and in 54 controls. Both were divided into 2 groups in accordance with sex. The 36 female patients were subdivided into 3 age-groups as follows: 8 aged 22-24, 10 aged 25-34, and 18 aged 35-50 while the male patients were gathered as one single group aged 26-57. The subdivision was adapted similarly for the normal age-grouts. Although no significant difference in SFL was found between the male control and the male patient groups, differences between the female control and female patient groups showed highly significant which levels, with the ascendance of age, were P【0.001, P【0.005 and P【0.001, respectively. Also the difference between male and female control groups were significant (P【0.05). However, no significant differences in SFL were discovered among the 3 patient groups. 10 female patients with SFL【12ng/ml were tested with ferrous sulfate for one month, then their SFL was reexamined one week after the treatment. A highly significant difference in SFL was noted between the pre-ad post-treatment (P【0.001). 9 of them showed that the interval of recurrences were prolonged, the number of ulcers reduced, the pain less intensive and its duration shorter than those before the treatment. This study demonstrated that a singificant decrease in iron-storage occurred in female RAU patients. The authors concluded that the decrease SFL was possibly related to menstruation and child bearing.

The Clinical Effects of Allantoin Powder for Gargle on Periodontal Diseases and Aphthous Ulcer

A newly developed mouthrinse, Allantoin Powder for Gargle, was clinically investigated. The compound of this agent is mainly allantoin, which is believed easy to penetrate into gingival sulcus and periodontal pockets as well as other places (such as tongue, soft palate, etc.) where it is inconvenient to use medication, 219 patients with various diseases of oral cavity were investigated in the double blind randomlized placebo controlled study. It was observed that apparent efficient rates of the experimental mouthrinse on periodontitis and marginal gingivitis were 81.25% and 56.86% respectively; and the efficient rate of it on aphthous ulcer was 68.57%. The data show that this agent has effective as an adjuctive on the treatments of periodontal diseases and aphthous ulcer.

Research Progress of Action Mechanism of Mongolian Medicine Hatageqi-7 in the Treatment of Recurrent Aphthous Ulcer

Based on Mongolian medical theory and modern pharmacology,literature on the main components and action mechanism of Hatageqi-7 in the treatment of recurrent aphthous ulcer is collected,sorted and summarized.The research hopes to provide certain basis for its clinical efficacy from theory.