{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:59:34Z","timestamp":1775804374468,"version":"3.50.1"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011447","name":"Science and Technology Department of Henan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011447","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Surg."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The comorbidity of type 2 diabetes mellitus (T2DM) and anal fistula is a prevalent global clinical challenge. Anal fistula is the second most common anorectal disease, with an incidence 1.81\u20132.01 times higher in diabetic patients than in the general population. Diabetic patients face elevated risks of postoperative infection, delayed healing, and recurrence, closely linked to poor preoperative glycemic control. Current strategies are mostly extrapolated from general population guidelines, failing to address the unique metabolic, immune, and microcirculatory abnormalities in this group, leading to suboptimal outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This narrative review followed PRISMA 2020 guidelines. We systematically searched PubMed, Embase, Cochrane Library, and CNKI for literature (2018\u2013June 2024) on T2DM complicated with cryptoglandular anal fistula, including clinical studies, high-quality animal experiments, and systematic reviews. Exclusion criteria: type 1\/gestational diabetes, Crohn's-related fistulas, case reports (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009&amp;lt;\u200910). We synthesized evidence on surgical optimization, regenerative medicine, and perioperative glycemic management.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\u2460 Sphincter-preserving surgeries (LIFT, VAAFT, TROPIS, EAF) reduce incontinence risk; TROPIS achieved 87.6% long-term healing in diabetics, while EAF is well-established for complex fistulas. \u2461 Regenerative therapies (CGF, MSCs) promote healing; autologous MSC-based therapies yielded 68.4%\u201384.6% healing for complex fistulas, with superior safety\/operability vs. allogeneic products. \u2462 Preoperative HbA1c\u2009&amp;lt;\u20097.0% reduced infection to 8.2%, with perioperative glucose targets of 140\u2013180\u2005mg\/dL optimal; once-weekly insulin icodec improved compliance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Individualized multidisciplinary strategies tailored to fistula complexity and glycemic status are essential. Future large-scale RCTs in diabetic patients are needed to validate novel biomaterials and anti-inflammatory agents to optimize outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fsurg.2026.1776450","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:04:23Z","timestamp":1775801063000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pathophysiological mechanisms and clinical management of type 2 diabetes mellitus complicated with anal fistula"],"prefix":"10.3389","volume":"13","author":[{"given":"Linhui","family":"Li","sequence":"first","affiliation":[{"name":"Department of Anorectal Diseases, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine","place":["Zhengzhou, China"]},{"name":"The First Clinical Medical College of Henan University of Traditional Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuangxi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anorectal Diseases, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"436","DOI":"10.31083\/j.rcm.25.12.436","article-title":"Diabetes mellitus and cardiovascular disease: exploring epidemiology, pathophysiology, and treatment strategies","volume":"25","author":"Siam","year":"2024","journal-title":"Rev Cardiovasc Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e0307653","DOI":"10.1371\/journal.pone.0307653","article-title":"Evaluating the efficacy of multi-incision and tube-dragging therapy combined with laser closure for high horseshoe-shaped anal fistula: protocol of a prospective, randomized, controlled trial","volume":"19","author":"Yang","year":"2024","journal-title":"PLoS One"},{"key":"B3","doi-asserted-by":"publisher","first-page":"825166","DOI":"10.3389\/fsurg.2022.825166","article-title":"Efficacy and safety of sphincter-preserving surgery in the treatment of complex anal fistula: a network meta-analysis","volume":"9","author":"Huang","year":"2022","journal-title":"Front Surg"},{"key":"B4","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1007\/s00384-015-2417-9","article-title":"Prevalence and recurrence rate of perianal abscess\u2013a population-based study, Sweden 1997-2009","volume":"31","author":"Adamo","year":"2016","journal-title":"Int J Colorectal Dis"},{"key":"B5","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/S0140-6736(23)01364-1","article-title":"Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021","volume":"402","year":"2023","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e0329030","DOI":"10.1371\/journal.pone.0329030","article-title":"Risk factors for delayed wound healing after anal fistula surgery: protocol of a meta-analytic study","volume":"20","author":"Mei","year":"2025","journal-title":"PLoS One"},{"key":"B7","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s00384-023-04491-9","article-title":"Predictors of recurrence and long-term patient reported outcomes following surgical repair of anal fistula, a retrospective analysis","volume":"39","author":"Khan","year":"2024","journal-title":"Int J Colorectal Dis"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1119113","DOI":"10.3389\/fsurg.2023.1119113","article-title":"Clinical features and independent predictors of postoperative refractory trauma to anal fistula combined with T2DM: a propensity score-matched analysis - retrospective cohort study","volume":"10","author":"Tang","year":"2023","journal-title":"Front Surg"},{"key":"B9","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"Br Med J"},{"key":"B10","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.surg.2009.05.018","article-title":"To plug or not to plug: a cost-effectiveness analysis for complex anal fistula","volume":"147","author":"Adamina","year":"2010","journal-title":"Surgery"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e1003228","DOI":"10.1371\/journal.pmed.1003228","article-title":"Bariatric surgery for patients with type 2 diabetes mellitus requiring insulin: clinical outcome and cost-effectiveness analyses","volume":"17","author":"McGlone","year":"2020","journal-title":"PLoS Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"141525","DOI":"10.1016\/j.ijbiomac.2024.141525","article-title":"Multifunctional coaxial gelatin\/polylactic acid three-dimensional nanofibrous scaffolds for diabetic wounds","volume":"306","author":"Chen","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"125117","DOI":"10.1016\/j.ijpharm.2024.125117","article-title":"Mechanistic insights of diabetic wound: healing process, associated pathways and microRNA-based delivery systems","volume":"670","author":"Yadu","year":"2025","journal-title":"Int J Pharm"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1641318","DOI":"10.3389\/fendo.2025.1641318","article-title":"An impact of type 2 diabetes mellitus on NKT-like cell population in humans: a new insight into impaired immune response in hyperglycemia","volume":"16","author":"Adamska-Fita","year":"2025","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B15","doi-asserted-by":"publisher","first-page":"3163","DOI":"10.2147\/IJN.S365540","article-title":"Efficiency of multifunctional antibacterial hydrogels for chronic wound healing in diabetes: a comprehensive review","volume":"17","author":"Ji","year":"2022","journal-title":"Int J Nanomedicine"},{"key":"B16","doi-asserted-by":"publisher","first-page":"113763","DOI":"10.1016\/j.biopha.2022.113763","article-title":"Antibacterial activity and wound healing potential of Cycas thouarsii R.Br n-butanol fraction in diabetic rats supported with phytochemical profiling","volume":"155","author":"Binsuwaidan","year":"2022","journal-title":"Biomed Pharmacother"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1039\/D3BM01752A","article-title":"Efficient healing of diabetic wounds by MSC-EV-7A composite hydrogel via suppression of inflammation and enhancement of angiogenesis","volume":"12","author":"Long","year":"2024","journal-title":"Biomater Sci"},{"key":"B18","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.jdermsci.2019.09.002","article-title":"High glucose environment induces M1 macrophage polarization that impairs keratinocyte migration via TNF-\u03b1: an important mechanism to delay the diabetic wound healing","volume":"96","author":"Huang","year":"2019","journal-title":"J Dermatol Sci"},{"key":"B19","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1007\/s00018-022-04531-9","article-title":"Intestinal microbiota regulates diabetes and cancer progression by IL-1\u03b2 and NOX4 dependent signaling cascades","volume":"79","author":"Noureldein","year":"2022","journal-title":"Cell Mol Life Sci"},{"key":"B20","doi-asserted-by":"publisher","first-page":"5945","DOI":"10.1021\/acs.jafc.2c00891","article-title":"Metabolites of gut microbiota and possible implication in development of diabetes mellitus","volume":"70","author":"Guo","year":"2022","journal-title":"J Agric Food Chem"},{"key":"B21","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1016\/j.jcmgh.2022.11.009","article-title":"Dysfunctional extracellular matrix remodeling supports perianal fistulizing Crohn's disease by a mechanoregulated activation of the epithelial-to-mesenchymal transition","volume":"15","author":"Rizzo","year":"2023","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"6421","DOI":"10.3390\/jcm12196421","article-title":"Perioperative factors affecting the healing of rectovaginal fistula","volume":"12","author":"Satora","year":"2023","journal-title":"J Clin Med"},{"key":"B23","doi-asserted-by":"publisher","first-page":"114540","DOI":"10.1016\/j.biopha.2023.114540","article-title":"Human beta defensin-2 loaded PLGA nanoparticles impregnated in collagen-chitosan composite scaffold for the management of diabetic wounds","volume":"161","author":"Sanapalli","year":"2023","journal-title":"Biomed Pharmacother"},{"key":"B24","doi-asserted-by":"publisher","first-page":"116399","DOI":"10.1016\/j.bcp.2024.116399","article-title":"Unveiling therapeutic potential: adipose tissue-derived mesenchymal stem cells and their exosomes in the management of diabetes mellitus, wound healing, and chronic ulcers","volume":"226","author":"Ahmadieh-Yazdi","year":"2024","journal-title":"Biochem Pharmacol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"112613","DOI":"10.1016\/j.bioadv.2022.112613","article-title":"A multifunctional antibacterial and self-healing hydrogel laden with bone marrow mesenchymal stem cell-derived exosomes for accelerating diabetic wound healing","volume":"133","author":"Geng","year":"2022","journal-title":"Biomater Adv"},{"key":"B26","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s13287-023-03299-9","article-title":"Mesenchymal stem cells transplantation for perianal fistulas: a systematic review and meta-analysis of clinical trials","volume":"14","author":"Wang","year":"2023","journal-title":"Stem Cell Res Ther"},{"key":"B27","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1186\/s13287-020-02019-9","article-title":"Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: a prospective case-control study","volume":"11","author":"Zhang","year":"2020","journal-title":"Stem Cell Res Ther"},{"key":"B28","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1097\/JS9.0000000000001897","article-title":"Efficacy and safety of 13 surgical techniques for the treatment of complex anal fistula, non-Crohn CAF: a systematic review and network meta-analysis","volume":"110","author":"An","year":"2024","journal-title":"Int J Surg"},{"key":"B29","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1186\/s12902-024-01636-y","article-title":"The interplay between diabetes Mellitus and soft tissue infections in general surgical patients","volume":"24","author":"Cheng","year":"2024","journal-title":"BMC Endocr Disord"},{"key":"B30","doi-asserted-by":"publisher","first-page":"59","DOI":"10.15386\/mpr-2045","article-title":"Fistulectomy and incontinence: do we really need to worry?","volume":"95","author":"Maqbool","year":"2022","journal-title":"Med Pharm Rep"},{"key":"B31","doi-asserted-by":"publisher","first-page":"586891","DOI":"10.3389\/fsurg.2020.586891","article-title":"Advances in the treatment of anal fistula: a mini-review of recent five-year clinical studies","volume":"7","author":"Ji","year":"2021","journal-title":"Front Surg"},{"key":"B32","doi-asserted-by":"publisher","first-page":"210","DOI":"10.5144\/0256-4947.2016.210","article-title":"Evaluation of the cutting seton as a method of treatment for perianal fistula","volume":"36","author":"Raslan","year":"2016","journal-title":"Ann Saudi Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1097\/SLA.0000000000003981","article-title":"A multicenter randomized controlled trial comparing safety, efficacy, and cost-effectiveness of the Surgisis anal fistula plug versus surgeon\u2019s preference for transsphincteric fistula-in-ano: the FIAT trial","volume":"273","author":"Jayne","year":"2021","journal-title":"Ann Surg"},{"key":"B34","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1016\/j.surg.2019.09.012","article-title":"Ligation of intersphincteric fistula tract (LIFT) in treatment of anal fistula: an updated systematic review, meta-analysis, and meta-regression of the predictors of failure","volume":"167","author":"Emile","year":"2020","journal-title":"Surgery"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.21037\/atm-20-7154","article-title":"Efficacy of video-assisted anal fistula treatment combined with closure of the internal opening using a stapler for Parks II anal fistula","volume":"8","author":"Zhang","year":"2020","journal-title":"Ann Transl Med"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.29271\/jcpsp.2025.09.1101","article-title":"Video-Assisted Anal Fistula Treatment (VAAFT) for complex perianal fistulae with long-term follow-up","volume":"35","author":"Amir","year":"2025","journal-title":"J Coll Physicians Surg Pak"},{"key":"B37","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1007\/s10151-022-02614-z","article-title":"Video-assisted anal fistula treatment for complex anorectal fistulas in adults: a systematic review and meta-analysis","volume":"26","author":"Tian","year":"2022","journal-title":"Tech Coloproctol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"306","DOI":"10.3892\/etm.2024.12595","article-title":"Efficacy and safety of transanal opening of intersphincteric space in the treatment of high complex anal fistula: a metaanalysis","volume":"28","author":"Wang","year":"2024","journal-title":"Exp Ther Med"},{"key":"B39","doi-asserted-by":"publisher","first-page":"474","DOI":"10.3393\/ac.2022.01018.0145","article-title":"The management of complex fistula in ano by transanal opening of the intersphincteric space (TROPIS): short-term results","volume":"40","author":"Mishra","year":"2024","journal-title":"Ann Coloproctol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1111\/codi.15555","article-title":"Transanal opening of the intersphincteric space: a novel sphincter-sparing procedure to treat 325 high complex anal fistulas with long-term follow-up","volume":"23","author":"Garg","year":"2021","journal-title":"Colorectal Dis"},{"key":"B41","doi-asserted-by":"publisher","first-page":"700","DOI":"10.17235\/reed.2023.9644\/2023","article-title":"Filac\u00ae procedure for highly selected anal fistula patients: indications, safety and efficacy from an observational study at a tertiary referral center","volume":"115","author":"Blanco Ter\u00e9s","year":"2023","journal-title":"Rev Esp Enferm Dig"},{"key":"B42","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1007\/s10151-020-02225-6","article-title":"Laser treatment for anal fistulas: what are the pitfalls?","volume":"24","author":"Giamundo","year":"2020","journal-title":"Tech Coloproctol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"301","DOI":"10.3393\/ac.2020.00668.0095","article-title":"Endofistula laser ablation of fistula-in-ano: a new minimally invasive technique for the treatment of fistula-in-ano","volume":"38","author":"Lalhruaizela","year":"2022","journal-title":"Ann Coloproctol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"7660118","DOI":"10.1155\/2022\/7660118","article-title":"Autologous bioactive compound concentrated growth factor ameliorates fistula healing of anal fistula in a pig model and promotes proliferation and migration of human skin fibroblasts via regulating the MEK\/ERK pathway","volume":"2022","author":"Zhang","year":"2022","journal-title":"Oxid Med Cell Longev"},{"key":"B45","doi-asserted-by":"publisher","first-page":"120348","DOI":"10.1016\/j.carbpol.2022.120348","article-title":"Injectable carboxymethyl chitosan-genipin hydrogels encapsulating tea tree oil for wound healing","volume":"301","author":"Hu","year":"2023","journal-title":"Carbohydr Polym"},{"key":"B46","doi-asserted-by":"publisher","first-page":"eade1067","DOI":"10.1126\/sciadv.ade1067","article-title":"A nanofiber-hydrogel composite improves tissue repair in a rat model of Crohn\u2019s disease perianal fistulas","volume":"9","author":"Li","year":"2023","journal-title":"Sci Adv"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1021\/acsbiomaterials.4c02043","article-title":"Injectable DAT-ALG hydrogel mitigates senescence of loaded DPMSCs and boosts healing of perianal fistulas in Crohn\u2019s disease","volume":"11","author":"Gao","year":"2025","journal-title":"ACS Biomater Sci Eng"},{"key":"B48","doi-asserted-by":"publisher","first-page":"900439","DOI":"10.3389\/fphar.2022.900439","article-title":"The potential application of natural products in cutaneous wound healing: a review of preclinical evidence","volume":"13","author":"Liu","year":"2022","journal-title":"Front Pharmacol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"7573","DOI":"10.1097\/JS9.0000000000002125","article-title":"Efficacy and safety of stem cell therapy for fistula management: an overview of existing systematic reviews","volume":"110","author":"Tripathi","year":"2024","journal-title":"Int J Surg"},{"key":"B50","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1111\/apt.18359","article-title":"Evaluation of the effectiveness and safety of mesenchymal stem cell treatment in fistulising Crohn\u2019s disease: an international real-life retrospective multicentre cohort study","volume":"61","author":"Bacsur","year":"2025","journal-title":"Aliment Pharmacol Ther"},{"key":"B51","doi-asserted-by":"publisher","first-page":"e2407537","DOI":"10.1002\/advs.202407537","article-title":"Quaternized molecular brush-grafted injectable microgel with anti-inflammatory and drainage properties for efficient therapy of anal fistula","volume":"12","author":"Wang","year":"2025","journal-title":"Adv Sci (Weinh)"},{"key":"B52","doi-asserted-by":"publisher","first-page":"119357","DOI":"10.1016\/j.ijpharm.2020.119357","article-title":"Treatment of insulin resistance in obesity-associated type 2 diabetes mellitus through adiponectin gene therapy","volume":"583","author":"Banerjee","year":"2020","journal-title":"Int J Pharm"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1016\/j.cgh.2024.08.032","article-title":"Efficacy and safety of upadacitinib for perianal fistulizing Crohn's disease: a post hoc analysis of 3 phase 3 trials","volume":"23","author":"Colombel","year":"2025","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"S83","DOI":"10.2337\/dc22-S006","article-title":"6. Glycemic targets: standards of medical care in diabetes-2022","volume":"45","year":"2022","journal-title":"Diabetes Care"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.7326\/M23-1288","article-title":"Once-weekly insulin icodec with dosing guide app versus once-daily basal insulin analogues in insulin-naive type 2 diabetes (ONWARDS 5): a randomized trial","volume":"176","author":"Bajaj","year":"2023","journal-title":"Ann Intern Med"},{"key":"B56","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s42836-023-00174-7","article-title":"Prevention of surgical site infection: a ten-step approach","volume":"5","author":"Tarabichi","year":"2023","journal-title":"Arthroplasty"},{"key":"B57","doi-asserted-by":"publisher","first-page":"629","DOI":"10.3238\/arztebl.m2021.0221","article-title":"Blood sugar targets in surgical intensive care\u2014management and special considerations in patients with diabetes","volume":"118","author":"Roth","year":"2021","journal-title":"Dtsch Arztebl Int"},{"key":"B58","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1002\/ncp.10858","article-title":"Practical approach to clinical controversies in glycemic control for hospitalized surgical patients","volume":"37","author":"Ware","year":"2022","journal-title":"Nutr Clin Pract"},{"key":"B59","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1007\/s40259-024-00670-5","article-title":"Insulin icodec: first approval","volume":"38","author":"Blair","year":"2024","journal-title":"BioDrugs"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.4239\/wjd.v12.i8.1255","article-title":"Perioperative challenges in management of diabetic patients undergoing non-cardiac surgery","volume":"12","author":"Galway","year":"2021","journal-title":"World J Diabetes"},{"key":"B61","doi-asserted-by":"publisher","first-page":"109900","DOI":"10.1016\/j.diabres.2022.109900","article-title":"Roux-en-Y gastric bypass versus best medical treatment for type 2 diabetes mellitus in adults with body mass index between 27 and 32\u2005kg\/m2: a 5-year randomized controlled trial","volume":"188","author":"Cheng","year":"2022","journal-title":"Diabetes Res Clin Pract"},{"key":"B62","doi-asserted-by":"publisher","first-page":"3055","DOI":"10.3390\/molecules27103055","article-title":"Role of dipeptidyl peptidase 4 inhibitors in antidiabetic treatment","volume":"27","author":"Yin","year":"2022","journal-title":"Molecules"},{"key":"B63","doi-asserted-by":"publisher","first-page":"105659","DOI":"10.1016\/j.archoralbio.2023.105659","article-title":"Sitagliptin attenuates porphyromonas gingivalis virulence and inflammatory response in macrophage on titanium","volume":"149","author":"Tang","year":"2023","journal-title":"Arch Oral Biol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"683","DOI":"10.2174\/1874467214666210902115650","article-title":"Impact of sitagliptin on non-diabetic COVID-19 patients","volume":"15","author":"Al-Kuraishy","year":"2022","journal-title":"Curr Mol Pharmacol"},{"key":"B65","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.22038\/IJBMS.2022.64552.14202","article-title":"Dipeptidyl peptidase-4 inhibitor: sitagliptin down-regulated toll-like receptor 4 signaling pathway to reduce uterine injury in rats","volume":"25","author":"Rofaeil","year":"2022","journal-title":"Iran J Basic Med Sci"},{"key":"B66","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1080\/13813455.2021.1975758","article-title":"Dipeptedyl peptidase-4 (DPP-4) inhibitor downregulates HMGB1\/TLR4\/NF-\u03baB signaling pathway in a diabetic rat model of non-alcoholic fatty liver disease","volume":"130","author":"Allam","year":"2024","journal-title":"Arch Physiol Biochem"},{"key":"B67","doi-asserted-by":"publisher","first-page":"100763","DOI":"10.1016\/j.repbio.2023.100763","article-title":"The effect of sitagliptin combined with rosiglitazone on autophagy and inflammation in polycystic ovary syndrome by regulating PI3K\/AKT\/mTOR and TLR4\/NF-\u03baB pathway","volume":"23","author":"Ren","year":"2023","journal-title":"Reprod Biol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1038\/s41420-021-00625-7","article-title":"Dipeptidyl peptidase-4 (DPP4) inhibitor sitagliptin alleviates liver inflammation of diabetic mice by acting as a ROS scavenger and inhibiting the NF\u03baB pathway","volume":"7","author":"Wang","year":"2021","journal-title":"Cell Death Discov"},{"key":"B69","doi-asserted-by":"publisher","first-page":"3209","DOI":"10.1096\/fj.201902221R","article-title":"Kruppel-like factor 6 promotes macrophage inflammatory and hypoxia response","volume":"34","author":"Kim","year":"2020","journal-title":"FASEB J"},{"key":"B70","doi-asserted-by":"publisher","first-page":"106945","DOI":"10.1016\/j.intimp.2020.106945","article-title":"Long-term inhibition of dipeptidyl-peptidase 4 reduces islet infiltration and downregulates IL-1\u03b2 and IL-12 in NOD mice","volume":"88","author":"He","year":"2020","journal-title":"Int Immunopharmacol"},{"key":"B71","doi-asserted-by":"publisher","first-page":"4777","DOI":"10.3390\/ijms21134777","article-title":"NRF2, a transcription factor for stress response and beyond","volume":"21","author":"He","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B72","doi-asserted-by":"publisher","first-page":"1389670","DOI":"10.3389\/fphar.2024.1389670","article-title":"Sitagliptin ameliorates L-arginine-induced acute pancreatitis via modulating inflammatory cytokines expression and combating oxidative stress","volume":"15","author":"Eltahir","year":"2024","journal-title":"Front Pharmacol"},{"key":"B73","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1038\/s41419-021-04227-0","article-title":"Sitagliptin activates the p62-Keap1-Nrf2 signalling pathway to alleviate oxidative stress and excessive autophagy in severe acute pancreatitis-related acute lung injury","volume":"12","author":"Kong","year":"2021","journal-title":"Cell Death Dis"},{"key":"B74","doi-asserted-by":"publisher","first-page":"7459","DOI":"10.1016\/j.ajtr.2022.100763","article-title":"Influence of glimepiride plus sitagliptin on treatment outcome, blood glucose, and oxidative stress in diabetic patients","volume":"14","author":"Zhao","year":"2022","journal-title":"Am J Transl Res"},{"key":"B75","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.3390\/antiox10081168","article-title":"Sitagliptin modulates oxidative, nitrative and halogenative stress and inflammatory response in rat model of hepatic ischemia-reperfusion","volume":"10","author":"Trocha","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"B76","doi-asserted-by":"publisher","first-page":"9794","DOI":"10.1038\/s41598-023-36829-3","article-title":"Sitagliptin ameliorates busulfan-induced pulmonary and testicular injury in rats through antioxidant, anti-inflammatory, antifibrotic, and antiapoptotic effects","volume":"13","author":"Ali","year":"2023","journal-title":"Sci Rep"},{"key":"B77","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.3390\/antiox11071418","article-title":"Antioxidant effects of DPP-4 inhibitors in early stages of experimental diabetic retinopathy","volume":"11","author":"Ramos","year":"2022","journal-title":"Antioxidants (Basel)"},{"key":"B78","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1093\/ecco-jcc\/jjz181","article-title":"Ligation of the intersphincteric fistula tract and endorectal advancement flap for high perianal fistulas in Crohn\u2019s disease: a retrospective cohort study","volume":"14","author":"van Praag","year":"2020","journal-title":"J Crohns Colitis"},{"key":"B79","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1136\/bmj.39489.470347.AD","article-title":"GRADE: an emerging consensus on rating quality of evidence and strength of recommendations","volume":"336","author":"Guyatt","year":"2008","journal-title":"Br Med J"},{"key":"B80","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1002\/bjs5.50129","article-title":"Systematic review and meta-analysis of endorectal advancement flap and ligation of the intersphincteric fistula tract for cryptoglandular and Crohn\u2019s high perianal fistulas","volume":"3","author":"Stellingwerf","year":"2019","journal-title":"BJS Open"},{"key":"B81","doi-asserted-by":"publisher","first-page":"374","DOI":"10.4240\/wjgs.v14.i5.374","article-title":"Comparison between recent sphincter-preserving procedures for complex anal fistulas-ligation of intersphincteric tract vs transanal opening of intersphincteric space","volume":"14","author":"Garg","year":"2022","journal-title":"World J Gastrointest Surg"},{"key":"B82","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1007\/s13304-023-01607-4","article-title":"A pilot study on staged surgery by delta video-assisted anal fistula treatment (dVAAFT) for complex anal fistula","volume":"75","author":"La Torre","year":"2023","journal-title":"Updates Surg"}],"container-title":["Frontiers in Surgery"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fsurg.2026.1776450\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:04:25Z","timestamp":1775801065000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fsurg.2026.1776450\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,10]]},"references-count":82,"alternative-id":["10.3389\/fsurg.2026.1776450"],"URL":"https:\/\/doi.org\/10.3389\/fsurg.2026.1776450","relation":{},"ISSN":["2296-875X"],"issn-type":[{"value":"2296-875X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,10]]},"article-number":"1776450"}}