{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T19:16:11Z","timestamp":1793992571860,"version":"4.8.0"},"reference-count":135,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T00:00:00Z","timestamp":1654560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The project of Tutorial System of Medical Undergraduate in Lab Teaching and Management Center at Chongqing Medical University","award":["LTMCMTS202114"],"award-info":[{"award-number":["LTMCMTS202114"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and objectives: To compare the efficacy and safety of topical interventions used for recurrent aphthous stomatitis. Materials and Methods: This network meta-analysis was conducted in accordance with the PRISMA statement. We searched four electronic databases, PubMed, Web of Science (WOS), Cochrane Central Register of Controlled Trials and Embase, for randomized controlled trials reporting efficacy and safety data on topical interventions for recurrent aphthous stomatitis. We performed a quality evaluation using a methodology based on the Cochrane Handbook. Two authors independently extracted data on healing effect, size reduction effect, symptom reduction effect, recurrence and safety assessment. Network meta-analysis was then performed using ADDIS and RevMan. Results: A total of 72 trials (5272 subjects) involving 29 topical interventions were included. Honey, lnsulin liposome gel, laser, amlexanox, glycyrrhiza and triamcinolone had better efficacy performance. Probiotics and chlorhexidine helped to prolong ulcer intervals and reduce recurrence. Doxycycline and penicillin had a high risk of adverse events. Hematologic evaluation showed no preference. The rank possibility of size-reducing effect and symptom-reducing effect supported the short-term effect of laser and the long-term effect of probiotics. Conclusions: We recommend the use of laser as a short-term intervention during the exacerbation phase of RAS and probiotics as a long-term intervention during the exacerbation and remission phases of RAS.<\/jats:p>","DOI":"10.3390\/medicina58060771","type":"journal-article","created":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T00:10:33Z","timestamp":1654560633000},"page":"771","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Efficacy of Topical Intervention for Recurrent Aphthous Stomatitis: A Network Meta-Analysis"],"prefix":"10.3390","volume":"58","author":[{"given":"Hao","family":"Liu","sequence":"first","affiliation":[{"name":"College of Stomatology, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Tan","sequence":"additional","affiliation":[{"name":"College of Nursing, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gege","family":"Fu","sequence":"additional","affiliation":[{"name":"First Clinical College, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Chen","sequence":"additional","affiliation":[{"name":"The Center of Experimental Teaching Management, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Tan","sequence":"additional","affiliation":[{"name":"The Center of Experimental Teaching Management, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S363","DOI":"10.4103\/jpbs.JPBS_581_20","article-title":"Assessment of Prevalence of Recurrent Aphthous Stomatitis in the North Indian Population: A Cross-Sectional Study","volume":"13","author":"Kaur","year":"2021","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s00784-020-03611-y","article-title":"Lifetime prevalence of recurrent aphthous stomatitis and its related factors in Northern Iranian population: The PERSIAN Guilan Cohort Study","volume":"25","author":"Darjani","year":"2021","journal-title":"Clin. Oral. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"675888644","DOI":"10.1177\/03000605211017724","article-title":"Relationship between dietary factors and recurrent aphthous stomatitis in China: A cross-sectional study","volume":"49","author":"Xu","year":"2021","journal-title":"J. Int. Med. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1111\/odi.13303","article-title":"Depression symptoms and recurrent aphthous stomatitis\u2014Evidence from a population-based study in Indonesia","volume":"26","author":"Hariyani","year":"2020","journal-title":"Oral Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1590\/abd1806-4841.20186228","article-title":"Recurrent aphthous ulceration: An epidemiological study of etiological factors, treatment and differential diagnosis","volume":"93","author":"Queiroz","year":"2018","journal-title":"An. Bras. Dermatol."},{"key":"ref_6","first-page":"1155","article-title":"Oral Aphthous: Pathophysiology, Clinical Aspects and Medical Treatment","volume":"76","author":"Gasmi","year":"2021","journal-title":"Arch. Razi Inst."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"25739","DOI":"10.3402\/jom.v6.25739","article-title":"The oral microbiota of patients with recurrent aphthous stomatitis","volume":"6","author":"Bankvall","year":"2014","journal-title":"J. Oral Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1590\/1678-775720150203","article-title":"The presence of Helicobacter pylori in oral cavities of patients with leukoplakia and oral lichen planus","volume":"24","year":"2016","journal-title":"J. Appl. Oral Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"202","DOI":"10.4103\/ijpvm.IJPVM_403_18","article-title":"New Insights into Oral Cancer-Risk Factors and Prevention: A Review of Literature","volume":"11","author":"Irani","year":"2020","journal-title":"Int. J. Prev. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s00005-013-0261-y","article-title":"Etiopathogenesis of recurrent aphthous stomatitis and the role of immunologic aspects: Literature review","volume":"62","author":"Slebioda","year":"2014","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ludovichetti, F.S., Signoriello, A.G., Girotto, L., Del Dot, L., Piovan, S., and Mazzoleni, S. (Rev. Esp. Enferm. Dig., 2022). Oro-dental lesions in paediatric patients with coeliac disease: An observational retrospective clinical study, Rev. Esp. Enferm. Dig., Online ahead of print.","DOI":"10.17235\/reed.2022.8422\/2021"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.bjoms.2007.07.201","article-title":"Oral mucosal disease: Recurrent aphthous stomatitis","volume":"46","author":"Scully","year":"2008","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1080\/09546634.2017.1422079","article-title":"Recurrent aphthous ulceration: A review of potential causes and novel treatments","volume":"29","author":"Saikaly","year":"2018","journal-title":"J. Dermatolog. Treat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1080\/09629359891126","article-title":"Topical glucocorticoids and the skin\u2014Mechanisms of action: An update","volume":"7","author":"Ahluwalia","year":"1998","journal-title":"Mediat. Inflamm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1177\/10454411910020030201","article-title":"Tetracyclines inhibit connective tissue breakdown: New therapeutic implications for an old family of drugs","volume":"2","author":"Golub","year":"1991","journal-title":"Crit. Rev. Oral Biol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1111\/j.1601-0825.2011.01840.x","article-title":"Urban legends: Recurrent aphthous stomatitis","volume":"17","author":"Baccaglini","year":"2011","journal-title":"Oral Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"105198","DOI":"10.1016\/j.archoralbio.2021.105198","article-title":"Quantitative changes of Veillonella, Streptococcus, and Neisseria in the oral cavity of patients with recurrent aphthous stomatitis: A systematic review and meta-analysis","volume":"129","author":"Yuan","year":"2021","journal-title":"Arch. Oral Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1089\/pho.2008.2372","article-title":"Laser therapy in the tissue repair process: A literature review","volume":"28","author":"Almeida","year":"2010","journal-title":"Photomed. Laser Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1016\/j.tripleo.2005.07.035","article-title":"A prospective randomized controlled trial to determine if cryotherapy can reduce the pain of patients with minor form of recurrent aphthous stomatitis","volume":"101","author":"Arikan","year":"2006","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e281","DOI":"10.1016\/j.jcms.2013.10.006","article-title":"Silver nitrate cauterization: A treatment option for aphthous stomatitis","volume":"42","year":"2014","journal-title":"J. Cranio-Maxillofac. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s00784-020-03704-8","article-title":"Association between serum zinc levels and recurrent aphthous stomatitis: A meta-analysis with trial sequential analysis","volume":"25","author":"Halboub","year":"2021","journal-title":"Clin. Oral Investig."},{"key":"ref_22","first-page":"40","article-title":"Curcumin gel in the treatment of minor aphthous ulcer: A randomized, placebo-controlled trial","volume":"11","author":"Manifar","year":"2012","journal-title":"J. Med. Plants"},{"key":"ref_23","first-page":"206","article-title":"A controlled trial of a dissolving oral patch concerning glycyrrhiza (licorice) herbal extract for the treatment of aphthous ulcers","volume":"56","author":"Martin","year":"2008","journal-title":"Gen. Dent."},{"key":"ref_24","first-page":"691","article-title":"Efficacy of honey in comparison to topical corticosteroid for treatment of recurrent minor aphthous ulceration: A randomized, blind, controlled, parallel, double-center clinical trial","volume":"45","author":"Asiri","year":"2014","journal-title":"Quintessence Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7034390","DOI":"10.1155\/2017\/7034390","article-title":"Relative Efficacy of Quercetin Compared with Benzydamine Hydrochloride in Minor Aphthae: A Prospective, Parallel, Double Blind, Active Control, Preliminary Study","volume":"2017","author":"Pandya","year":"2017","journal-title":"Int. J. Dent."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6912","DOI":"10.19082\/6912","article-title":"Effect of 0.5% Chitosan mouthwash on recurrent aphthous stomatitis: A randomized double-blind crossover clinical trial","volume":"10","author":"Rahmani","year":"2018","journal-title":"Electron. Physician"},{"key":"ref_27","first-page":"381","article-title":"Evaluation of the therapeutic effects of Aloe vera gel on minor recurrent aphthous stomatitis","volume":"9","author":"Babaee","year":"2012","journal-title":"Dent. Res. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.oooo.2012.09.009","article-title":"Effects of berberine gelatin on recurrent aphthous stomatitis: A randomized, placebo-controlled, double-blind trial in a Chinese cohort","volume":"115","author":"Jiang","year":"2013","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.oooo.2013.07.003","article-title":"Double-blind, randomized, controlled clinical trial of the effects of diosmectite and basic fibroblast growth factor paste on the treatment of minor recurrent aphthous stomatitis","volume":"116","author":"Jiang","year":"2013","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.oooo.2011.09.007","article-title":"Clinical evaluation of allicin oral adhesive tablets in the treatment of recurrent aphthous ulceration","volume":"113","author":"Jiang","year":"2012","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/jop.12232","article-title":"Recurrent aphthous stomatitis (RAS): A preliminary within-subject study of quality of life, oral health impacts and personality profiles","volume":"44","author":"Karasneh","year":"2015","journal-title":"J. Oral Pathol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"21181","DOI":"10.1038\/s41598-020-78281-7","article-title":"The efficacy of probiotics in management of recurrent aphthous stomatitis: A systematic review and meta-analysis","volume":"10","author":"Cheng","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Al-Maweri, S.A., Halboub, E., Ashraf, S., Alqutaibi, A.Y., Qaid, N.M., Yahya, K., and Alhajj, M.N. (2020). Single application of topical doxycycline in management of recurrent aphthous stomatitis: A systematic review and meta-analysis of the available evidence. BMC Oral Health, 20.","DOI":"10.1186\/s12903-020-01220-5"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"101349","DOI":"10.1016\/j.jebdp.2019.101349","article-title":"Limited Evidence Suggests That Patients with Recurrent Aphthous Stomatitis May Benefit from Using Sodium Lauryl Sulfate-free Dentifrices","volume":"19","author":"Cheng","year":"2019","journal-title":"J. Evid. Based Dent. Pract."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.jid.2018.10.028","article-title":"Research Techniques Made Simple: Network Meta-Analysis","volume":"139","author":"Watt","year":"2019","journal-title":"J. Invest. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"777","DOI":"10.7326\/M14-2385","article-title":"The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: Checklist and explanations","volume":"162","author":"Hutton","year":"2015","journal-title":"Ann. Intern. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.dss.2012.10.005","article-title":"ADDIS: A decision support system for evidence-based medicine","volume":"55","author":"Tervonen","year":"2013","journal-title":"Decis. Support Syst."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1007\/s10103-020-03166-0","article-title":"Effect of different treatments on recurrent aphthous stomatitis: Laser versus medication","volume":"36","author":"Huo","year":"2021","journal-title":"Lasers Med. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8867548","DOI":"10.1155\/2020\/8867548","article-title":"A Clinic Trial Evaluating the Effects of Aloe Vera Fermentation Gel on Recurrent Aphthous Stomatitis","volume":"2020","author":"Shi","year":"2020","journal-title":"Can. J. Infect. Dis. Med. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1111\/jocd.13110","article-title":"Lactic acid 5% mouth wash vs Kenalog in Orabase 0.1% for treatment and prophylaxis of recurrent aphthous ulcer","volume":"19","author":"Ibrahim","year":"2020","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"95","DOI":"10.4103\/jrms.JRMS_748_19","article-title":"Penicillin in oral aphthosis, new insight for an old drug: A randomized, double-blind, controlled clinical trial","volume":"25","author":"Owlia","year":"2020","journal-title":"J. Res. Med. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"884","DOI":"10.5005\/jp-journals-10024-2901","article-title":"Topical Curcumin and Triamcinolone Acetonide in Recurrent Minor Aphthous Ulcers: A Pilot Trial","volume":"21","author":"Raman","year":"2020","journal-title":"J. Contemp. Dent. Pract."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1080\/09546634.2019.1688231","article-title":"N-acetylcysteine versus chlorhexidine in treatment of aphthous ulcers: A preliminary clinical trial","volume":"32","author":"Halboub","year":"2019","journal-title":"J. Dermatol. Treat."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e12437","DOI":"10.1111\/jicd.12437","article-title":"Topical insulin-liposomal formulation in management of recurrent aphthous ulcers: A randomized placebo-controlled trial","volume":"10","author":"Dawoud","year":"2019","journal-title":"J. Investig. Clin. Dent."},{"key":"ref_45","first-page":"184","article-title":"Comparative Study of Punica granatum Gel and Triadent Oral Paste Effect on Recurrent Aphthous Stomatitis, a Double Blind Clinical Trial","volume":"20","author":"Tavangar","year":"2019","journal-title":"J. Dent."},{"key":"ref_46","first-page":"17","article-title":"Clinical Evaluation of High and Low-Level Laser Treatment (CO2vsInGaAlP Diode Laser) for Recurrent Aphthous Stomatitis","volume":"18","author":"Zeini","year":"2017","journal-title":"J. Dent."},{"key":"ref_47","first-page":"55","article-title":"Randomized clinical trial of the effectiveness of complementary therapies for recurrent aphthous stomatitis","volume":"149","author":"Raissouni","year":"2017","journal-title":"Med. Clin."},{"key":"ref_48","first-page":"1331","article-title":"Comparison effectiveness of the bioadhesive paste containing licorice 5% with bioadhesive paste without drug in the management of recurrent aphthous stomatitis","volume":"31","author":"Raeesi","year":"2015","journal-title":"Acta Med. Mediterr."},{"key":"ref_49","first-page":"218","article-title":"Efficacy of low-level laser therapy in treatment of recurrent aphthous ulcers\u2014A sham controlled, split mouth follow up study","volume":"8","author":"Aggarwal","year":"2014","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"138","DOI":"10.4103\/2230-973X.138346","article-title":"Comparison of effectiveness of curcumin with triamcinolone acetonide in the gel form in treatment of minor recurrent aphthous stomatitis: A randomized clinical trial","volume":"4","author":"Deshmukh","year":"2014","journal-title":"Int. J. Pharm. Investig."},{"key":"ref_51","first-page":"986203","article-title":"The Efficacy of Sucralfate and Chlorhexidine as an Oral Rinse in Patients with Recurrent Aphthous Stomatitis","volume":"2014","author":"Soylu","year":"2014","journal-title":"Adv. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.oooo.2013.02.011","article-title":"Assessment of immediate pain relief with laser treatment in recurrent aphthous stomatitis","volume":"116","author":"Prasad","year":"2013","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.oooo.2013.06.015","article-title":"Single application of topical doxycycline hyclate in the management of recurrent aphthous stomatitis","volume":"116","author":"Vijayabala","year":"2013","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1089\/pho.2012.3301","article-title":"Promoting wound healing in minor recurrent aphthous stomatitis by non-thermal, non-ablative CO2 laser therapy: A pilot study","volume":"30","author":"Zand","year":"2012","journal-title":"Photomed. Laser Surg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1002\/ptr.2601","article-title":"The efficacy of the bioadhesive patches containing licorice extract in the management of recurrent aphthous stomatitis","volume":"23","author":"Moghadamnia","year":"2009","journal-title":"Phytother. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/S1079-2104(98)90344-4","article-title":"Effectiveness of a medicament containing silicon dioxide, aloe, and allantoin on aphthous stomatitis","volume":"86","author":"Garnick","year":"1998","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/sj.bdj.4808250","article-title":"A clinical trial of prostaglandin E2 in recurrent aphthous ulceration","volume":"175","author":"Taylor","year":"1993","journal-title":"Brit. Dent. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/sj.bdj.4806042","article-title":"Chlorhexidine gluconate mouthwash in the management of minor aphthous ulceration. A double-blind, placebo-controlled cross-over trial","volume":"162","author":"Hunter","year":"1987","journal-title":"Brit. Dent. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/sj.bdj.4803798","article-title":"Management of recurrent aphthous ulceration. A trial of chlorhexidine gluconate gel","volume":"141","author":"Addy","year":"1976","journal-title":"Br. Dent. J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/sj.bdj.4803212","article-title":"Trial of astringent and antibacterial mouthwashes in the management of recurrent aphthous ulceration","volume":"136","author":"Addy","year":"1974","journal-title":"Br. Dent. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1007\/s00784-020-03527-7","article-title":"Evaluation of the effect of probiotic lozenges in the treatment of recurrent aphthous stomatitis: A randomized, controlled clinical trial","volume":"25","author":"Aggour","year":"2021","journal-title":"Clin. Oral Invest."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"S444","DOI":"10.4103\/jpbs.JPBS_133_20","article-title":"Assessment of efficacy of 5% topical amlexanox and 0.1% topical triamcinolone acetonide in management of recurrent aphthous stomatitis","volume":"12","author":"Kavita","year":"2020","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1080\/09546634.2019.1610548","article-title":"Clinical evaluation of an oral mucoadhesive film containing chitosan for the treatment of recurrent aphthous stomatitis: A randomized, double-blind study","volume":"31","author":"Shao","year":"2020","journal-title":"J. Dermatol. Treat."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Ghorbani, A., Akbari, J., Boorboor, M., Nekoukar, Z., and Eslami, G. (2020). Evaluation of zinc sulfate mucoadhesive formulation on recurrent aphthous stomatitis: A randomized double-blind, placebo-controlled clinical trial. BMC Oral Health, 20.","DOI":"10.1186\/s12903-020-01194-4"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"100336","DOI":"10.1016\/j.hermed.2020.100336","article-title":"New concentration of curcumin orabase in recurrent aphthous stomatitis: A randomized, controlled clinical trial","volume":"22","author":"Kia","year":"2020","journal-title":"J. Herb. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e549","DOI":"10.4317\/medoral.23573","article-title":"Photobiomodulation therapy for the management of recurrent aphthous sto-matitis in children: Clinical effectiveness and parental satisfaction","volume":"25","author":"Bardellini","year":"2020","journal-title":"Med. Oral Patol. Oral"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"S67","DOI":"10.34172\/jlms.2020.S11","article-title":"The Effect of Carbon Dioxide Laser on Aphthous stomatitis Treatment: A Double-Blind Randomized Clinical Trial","volume":"11","author":"Seyyedi","year":"2020","journal-title":"J. Lasers Med. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s12070-017-1139-9","article-title":"A Study to Assess the Efficacy of Local Application of Oral Probiotic in Treating Recurrent Aphthous Ulcer and Oral Candidiasis","volume":"71","author":"Nirmala","year":"2019","journal-title":"Indian J. Otolaryngol. Head Neck Surg."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.3889\/oamjms.2019.268","article-title":"Clinical evaluation of 660 nm diode laser therapy on the pain, size and functional disorders of recurrent aphthous stomatitis","volume":"7","author":"Soliman","year":"2019","journal-title":"Open Access Maced. J. Med. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"700","DOI":"10.2174\/1745017901814010700","article-title":"A Randomized, Double-Blind, Placebo-Controlled Trial on Clinical Efficacy of Topical Agents in Reducing Pain and Frequency of Recurrent Aphthous Ulcers","volume":"12","author":"Sharma","year":"2018","journal-title":"Open Dent. J."},{"key":"ref_71","first-page":"e159","article-title":"An evaluation of the efficacy of a topical gel with Triester Glycerol Oxide (TGO) in the treatment of minor recurrent aphthous stomatitis in a turkish cohort: A randomized, double-blind, placebo-controlled clinical trial","volume":"22","author":"Ofluoglu","year":"2017","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"ref_72","first-page":"e517","article-title":"Different modalities for treatment of recurrent aphthous stomatitis. A randomized clinical trial","volume":"8","author":"Nasry","year":"2016","journal-title":"J. Clin. Exp. Dent."},{"key":"ref_73","first-page":"e368","article-title":"Effectiveness of Amlexanox and Adcortyl for the treatment of recurrent aphthous ulcers","volume":"8","author":"Abbasi","year":"2016","journal-title":"J. Clin. Exp. Dent."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.hermed.2015.05.001","article-title":"The effect of Matricaria chamomilla (chamomile) extract in Orabase on minor aphthous stomatitis, a randomized clinical trial","volume":"5","author":"Pourshahidi","year":"2015","journal-title":"J. Herb. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/jop.12130","article-title":"Clinical efficacy of new aloe vera- and myrrh-based oral mucoadhesive gels in the management of minor recurrent aphthous stomatitis: A randomized, double-blind, vehicle-controlled study","volume":"43","author":"Mansour","year":"2014","journal-title":"J. Oral Pathol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"593","DOI":"10.4103\/0970-9290.123382","article-title":"A clinical evaluation of 5% amlexanox oral paste in the treatment of minor recurrent aphthous ulcers and comparison with the placebo paste: A randomized, vehicle controlled, parallel, single center clinical trial","volume":"24","author":"Bhat","year":"2013","journal-title":"Indian J. Dent. Res. Off. Publ. Indian Soc. Dent. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1089\/acm.2012.0164","article-title":"Acemannan, a polysaccharide extracted from aloe vera, is effective in the treatment of oral aphthous ulceration","volume":"19","author":"Bhalang","year":"2013","journal-title":"J. Altern. Complem. Med."},{"key":"ref_78","first-page":"392","article-title":"Novel material in the treatment of minor oral recurrent aphthous stomatitis","volume":"20","author":"Halim","year":"2013","journal-title":"Int. Med. J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"283","DOI":"10.5978\/islsm.13-OR-24","article-title":"A clinical efficacy of using CO2 laser irradiating to transparent gel on aphthous stomatitis patients","volume":"22","author":"Sattayut","year":"2013","journal-title":"Laser Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.amjmed.2011.09.011","article-title":"Efficacy and safety of dexamethasone ointment on recurrent aphthous ulceration","volume":"125","author":"Liu","year":"2012","journal-title":"Am. J. Med."},{"key":"ref_81","first-page":"2398","article-title":"Therapeutic Efficacy of Herbal Formulations for Recurrent Aphthous Ulcer. Correlation with Salivary Epidermal Growth Factor","volume":"9","author":"Galal","year":"2012","journal-title":"Life Sci. J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1745-6215-10-30","article-title":"A clinical evaluation of amlexanox oral adhesive pellicles in the treatment of recurrent aphthous stomatitis and comparison with amlexanox oral tablets: A randomized, placebo controlled, blinded, multicenter clinical trial","volume":"10","author":"Meng","year":"2009","journal-title":"Trials"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.tripleo.2005.12.014","article-title":"An evaluation on the efficacy and safety of amlexanox oral adhesive tablets in the treatment of recurrent minor aphthous ulceration in a Chinese cohort: A randomized, double-blind, vehicle-controlled, unparallel multicenter clinical trial","volume":"102","author":"Liu","year":"2006","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/S1079-2104(97)90009-3","article-title":"5% amlexanox oral paste, a new treatment for recurrent minor aphthous ulcers: I. Clinical demonstration of acceleration of healing and resolution of pain","volume":"83","author":"Khandwala","year":"1997","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s12602-019-09586-x","article-title":"Effect of Lozenges Containing Lactobacillus reuteri on the Severity of Recurrent Aphthous Ulcers: A Pilot Study","volume":"12","author":"Pedersen","year":"2020","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jphotobiol.2017.03.011","article-title":"Treatment of recurrent aphthous stomatitis with Er,Cr:YSGG laser irradiation: A randomized controlled split mouth clinical study","volume":"170","author":"Yilmaz","year":"2017","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1089\/pho.2008.2274","article-title":"An evaluation of different treatments for recurrent aphthous stomatitis and patient perceptions: Nd:YAG laser versus medication","volume":"27","author":"Tezel","year":"2009","journal-title":"Photomed. Laser Surg."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1080\/00016350802526559","article-title":"Clinical assessment of the effect of a matrix metalloproteinase inhibitor on aphthous ulcers","volume":"67","author":"Skulason","year":"2009","journal-title":"Acta Odontol. Scand."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s10103-008-0555-1","article-title":"Relieving pain in minor aphthous stomatitis by a single session of non-thermal carbon dioxide laser irradiation","volume":"24","author":"Zand","year":"2009","journal-title":"Laser. Med. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S1079-2104(97)90238-9","article-title":"Doxymycine-cyanoacrylate treatment of recurrent aphthous ulcers","volume":"83","author":"Ylikontiola","year":"1997","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/0030-4220(93)90158-Z","article-title":"Triamcinolone acetonide versus chlorhexidine for treatment of recurrent stomatitis","volume":"75","author":"Miles","year":"1993","journal-title":"Oral Surg. Oral Med. Oral Pathol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.oooo.2014.01.228","article-title":"Recurrent aphthous stomatitis and pain management with low-level laser therapy: A randomized controlled trial","volume":"117","author":"Albrektson","year":"2014","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"439425","DOI":"10.1155\/2011\/439425","article-title":"Use of lozenges containing Lactobacillus brevis CD2 in recurrent aphthous stomatitis: A double-blind placebo-controlled trial","volume":"2011","author":"Trinchieri","year":"2011","journal-title":"Ulcers"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1754-4505.2008.00006.x","article-title":"Topical minocycline for managing symptoms of recurrent aphthous stomatitis","volume":"28","author":"Gorsky","year":"2008","journal-title":"Spec. Care Dent."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1111\/j.1601-0825.2006.01327.x","article-title":"Effectiveness of two oral pastes for the treatment of recurrent aphthous stomatitis","volume":"13","author":"Rubio","year":"2007","journal-title":"Oral Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0278-2391(10)80164-8","article-title":"A double-blind study of topically applied 5% amlexanox in the treatment of aphthous ulcers","volume":"51","author":"Greer","year":"1993","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0030-4220(87)90310-0","article-title":"Clinical evaluation of benzydamine, chlorhexidine, and placebo mouthwashes in the management of recurrent aphthous stomatitis","volume":"63","author":"Matthews","year":"1987","journal-title":"Oral Surg. Oral Med. Oral Pathol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0140-6736(68)92833-X","article-title":"Topical triamcinolone acetonide in recurrent aphthous stomatitis. A clinical trial","volume":"1","author":"Browne","year":"1968","journal-title":"Lancet"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"283","DOI":"10.2741\/1184","article-title":"Wound healing: An overview of acute, fibrotic and delayed healing","volume":"9","author":"Diegelmann","year":"2004","journal-title":"Front. Biosci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"e2021099","DOI":"10.5826\/dpc.1104a99","article-title":"Recurrent Aphthous Stomatitis: Treatment and Management","volume":"11","author":"Manfredini","year":"2021","journal-title":"Dermatol. Pract. Concept."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Daug\u0117lait\u0117, G., U\u017ekuraityt\u0117, K., Jagelavi\u010dien\u0117, E., and Filipauskas, A. (2019). Prevention and Treatment of Chemotherapy and Radiotherapy Induced Oral Mucositis. Medicina, 55.","DOI":"10.3390\/medicina55020025"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.jobcr.2020.05.004","article-title":"Treatment outcomes of laser therapy in oral submucous fibrosis\u2014A systematic review","volume":"10","author":"Gondivkar","year":"2020","journal-title":"J. Oral Biol. Craniofac. Res."},{"key":"ref_103","first-page":"351","article-title":"Treatment of oral lichen planus. Systematic review and therapeutic guide","volume":"149","year":"2017","journal-title":"Med. Clin."},{"key":"ref_104","first-page":"D1829","article-title":"Interventions for treating oral leukoplakia to prevent oral cancer","volume":"7","author":"Lodi","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e216","DOI":"10.4317\/medoral.24144","article-title":"Efficacy of the laser at low intensity on primary burning oral syndrome: A systematic review","volume":"26","author":"Matos","year":"2021","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.ramb.2013.08.003","article-title":"Laser therapy in the control of oral mucositis: A meta-analysis","volume":"59","author":"Figueiredo","year":"2013","journal-title":"Rev. Assoc. Med. Bras."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1590\/S0103-64402011000200013","article-title":"Laser phototherapy as a treatment for radiotherapy-induced oral mucositis","volume":"22","author":"Lino","year":"2011","journal-title":"Braz. Dent. J."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.jphotobiol.2006.10.002","article-title":"Evaluation of mitochondrial respiratory chain activity in wound healing by low-level laser therapy","volume":"86","author":"Silveira","year":"2007","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1089\/pho.2005.23.355","article-title":"Exact action spectra for cellular responses relevant to phototherapy","volume":"23","author":"Karu","year":"2005","journal-title":"Photomed. Laser Surg."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/lsm.10126","article-title":"Influence of low level laser therapy on wound healing and its biological action upon myofibroblasts","volume":"32","author":"Medrado","year":"2003","journal-title":"Lasers Surg. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1007\/s10103-017-2184-z","article-title":"Effect of laser on pain relief and wound healing of recurrent aphthous stomatitis: A systematic review","volume":"32","author":"Suter","year":"2017","journal-title":"Lasers Med. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"9062430","DOI":"10.1155\/2016\/9062430","article-title":"Effectiveness of Laser Therapy in the Management of Recurrent Aphthous Stomatitis: A Systematic Review","volume":"2016","author":"Han","year":"2016","journal-title":"Scientifica"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.medici.2016.07.006","article-title":"Management of recurrent aphthous ulcers using low-level lasers: A systematic review","volume":"52","author":"Najeeb","year":"2016","journal-title":"Medicina"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"722","DOI":"10.2298\/VSP140410028P","article-title":"Treatment of recurrent aphthous stomatitis by laser therapy: A systematic review of the literature","volume":"72","author":"Aoki","year":"2015","journal-title":"Vojnosanit. Pregl."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"5522","DOI":"10.2174\/138161212803307473","article-title":"Probiotics and oral health","volume":"18","author":"Bizzini","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/odi.12899","article-title":"Biodiversity of the human oral mycobiome in health and disease","volume":"25","author":"Bandara","year":"2019","journal-title":"Oral Dis."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1159\/000345367","article-title":"Dental caries from a molecular microbiological perspective","volume":"47","author":"Nyvad","year":"2013","journal-title":"Caries Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/j.1600-0757.2011.00413.x","article-title":"Global periodontal disease epidemiology","volume":"58","author":"Dye","year":"2012","journal-title":"Periodontol. 2000"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.cden.2016.12.004","article-title":"Oral Fungal Infections: Diagnosis and Management","volume":"61","author":"Telles","year":"2017","journal-title":"Dent. Clin. North Am."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jdent.2016.03.002","article-title":"Probiotics for managing caries and periodontitis: Systematic review and meta-analysis","volume":"48","author":"Gruner","year":"2016","journal-title":"J. Dent."},{"key":"ref_121","first-page":"255","article-title":"Probiotics in the dental practice: A review","volume":"46","author":"Laleman","year":"2015","journal-title":"Quintessence Int."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1007\/s00784-014-1228-z","article-title":"Probiotics reduce mutans streptococci counts in humans: A systematic review and meta-analysis","volume":"18","author":"Laleman","year":"2014","journal-title":"Clin. Oral Investig."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1111\/jcpe.12464","article-title":"The effect of a streptococci containing probiotic in periodontal therapy: A randomized controlled trial","volume":"42","author":"Laleman","year":"2015","journal-title":"J. Clin. Periodontol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1111\/j.1600-051X.2008.01306.x","article-title":"Improvement of periodontal condition by probiotics with Lactobacillus salivarius WB21: A randomized, double-blind, placebo-controlled study","volume":"35","author":"Shimauchi","year":"2008","journal-title":"J. Clin. Periodontol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"026009","DOI":"10.1088\/1752-7163\/abcd2b","article-title":"Alternative therapies in controlling oral malodour: A systematic review","volume":"15","author":"Wylleman","year":"2021","journal-title":"J. Breath Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"46010","DOI":"10.1088\/1752-7163\/aacf49","article-title":"Efficacy of probiotics: Clinical and microbial parameters of halitosis","volume":"12","author":"Georgiou","year":"2018","journal-title":"J. Breath Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"15646","DOI":"10.1038\/s41598-021-95228-8","article-title":"Salivary proteome of aphthous stomatitis reveals the participation of vitamin metabolism, nutrients, and bacteria","volume":"11","author":"Pereira","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.amjoto.2005.09.022","article-title":"Recurrent aphthous stomatitis: Investigation of possible etiologic factors","volume":"27","author":"Koybasi","year":"2006","journal-title":"Am. J. Otolaryngol."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Cappello, F., Rappa, F., Canepa, F., Carini, F., Mazzola, M., Tomasello, G., Bonaventura, G., Giuliana, G., Leone, A., and Saguto, D. (2019). Probiotics Can Cure Oral Aphthous-Like Ulcers in Inflammatory Bowel Disease Patients: A Review of the Literature and a Working Hypothesis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20205026"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/lam.12434","article-title":"An assessment of adhesion, aggregation and surface charges of Lactobacillus strains derived from the human oral cavity","volume":"61","author":"Piwat","year":"2015","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1177\/0022034515606045","article-title":"Oral Microbiome Metabolism: From \u201cWho Are They?\u201d to \u201cWhat Are They Doing?\u201d","volume":"94","author":"Takahashi","year":"2015","journal-title":"J. Dent. Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1590\/S1806-83242012000700010","article-title":"Are we ready for caries prevention through bacteriotherapy?","volume":"26","author":"Twetman","year":"2012","journal-title":"Braz. Oral Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1159\/000496426","article-title":"Beneficial Effects of Probiotic Consumption on the Immune System","volume":"74","author":"Maldonado","year":"2019","journal-title":"Ann. Nutr. Metab."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1055\/s-0039-1697851","article-title":"Probiotics and oral health","volume":"4","author":"Haukioja","year":"2010","journal-title":"Eur. J. Dent."},{"key":"ref_135","first-page":"329","article-title":"Probiotics: Health benefits in the mouth","volume":"22","author":"Stamatova","year":"2009","journal-title":"Am. J. Dent."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/6\/771\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:25:13Z","timestamp":1760138713000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/6\/771"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,7]]},"references-count":135,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["medicina58060771"],"URL":"https:\/\/doi.org\/10.3390\/medicina58060771","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,7]]}}}