{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T11:17:22Z","timestamp":1793531842954,"version":"4.5.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Peptic ulcer refers to the inflammatory response and necrotic lesions of the mucosa under the action of various pathogenic factors, which goes deeply into the mucosal muscle layer and often occurs to the gastrointestinal mucosa related to gastric acid secretion, among which the stomach and duodenum are the most common. The clinical manifestations include slow onset, prolonged course and weekly upper abdominal pain. Nitric oxide (NO) is an intracellular and intercellular signaling molecule that plays an important role in many physiological and pathological processes. Studies have found that a small amount of NO produced\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      plays a role in many physiological homeostasis, such as regulating blood pressure, platelet aggregation, nitrogenization of hemoglobin, and regulating proliferation and differentiation of stem cells. However, under the action of some cytokines and oxidative stress, intracellular NO synthase will catalyze the synthesis of large amounts of NO and participate in the inflammatory response, causing beneficial or harmful effect on the body. Numerous basic studies have focused on the relationship between NO and peptic ulcer. The purpose of this review is to summarize the role of NO in peptic ulcer and its possible mechanism.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/2045-9912.310059","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:03:37Z","timestamp":1614125017000},"page":"42-45","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":48,"title":["The role of nitric oxide in peptic ulcer"],"prefix":"10.4103","volume":"11","author":[{"given":"Tian-Yu","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru-Ming","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-8-20240907","doi-asserted-by":"crossref","first-page":"l5495","DOI":"10.1136\/bmj.l5495","article-title":"Peptic ulcer disease","volume":"367","author":"Sverd\u00e9n","year":"2019","journal-title":"BMJ"},{"key":"R2-8-20240907","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0300-2977(96)00075-7","article-title":"The clinical presentation of peptic ulcer disease","volume":"50","author":"Werdmuller","year":"1997","journal-title":"Neth J Med"},{"key":"R3-8-20240907","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1111\/j.1365-2036.2009.03960.x","article-title":"Systematic review: the global incidence and prevalence of peptic ulcer disease","volume":"29","author":"Sung","year":"2009","journal-title":"Aliment Pharmacol Ther"},{"key":"R4-8-20240907","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1111\/j.1365-2036.2009.04131.x","article-title":"Uncomplicated peptic ulcer in the UK: trends from 1997 to 2005","volume":"30","author":"Cai","year":"2009","journal-title":"Aliment Pharmacol Ther"},{"key":"R5-8-20240907","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.dld.2008.02.024","article-title":"Time, change and peptic ulcer disease in Rotherham, UK","volume":"40","author":"Bardhan","year":"2008","journal-title":"Dig Liver Dis"},{"key":"R6-8-20240907","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1093\/aje\/kwj129","article-title":"Peptic ulcer disease in a general adult population: the Kalixanda study: a random population-based study","volume":"163","author":"Aro","year":"2006","journal-title":"Am J Epidemiol"},{"key":"R7-8-20240907","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1177\/2050640615623369","article-title":"Towards a healthy stomach? Helicobacter pylori prevalence has dramatically decreased over 23 years in adults in a Swedish community","volume":"4","author":"Agr\u00e9us","year":"2016","journal-title":"United European Gastroenterol J"},{"key":"R8-8-20240907","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1111\/apt.13550","article-title":"Time trends in upper gastrointestinal diseases and Helicobacter pylori infection in a multiracial Asian population--a 20-year experience over three time periods","volume":"43","author":"Leow","year":"2016","journal-title":"Aliment Pharmacol Ther"},{"key":"R9-8-20240907","doi-asserted-by":"crossref","first-page":"439","DOI":"10.5694\/j.1326-5377.1985.tb113444.x","article-title":"Pyloric Campylobacter infection and gastroduodenal disease","volume":"142","author":"Marshall","year":"1985","journal-title":"Med J Aust"},{"key":"R10-8-20240907","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1093\/infdis\/157.4.777","article-title":"Effect of age on the frequency of active Campylobacter pylori infection diagnosed by the [13C]urea breath test in normal subjects and patients with peptic ulcer disease","volume":"157","author":"Graham","year":"1988","journal-title":"J Infect Dis"},{"key":"R11-8-20240907","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1056\/NEJM199607253350404","article-title":"The risk of stomach cancer in patients with gastric or duodenal ulcer disease","volume":"335","author":"Hansson","year":"1996","journal-title":"N Engl J Med"},{"key":"R12-8-20240907","doi-asserted-by":"crossref","first-page":"g3174","DOI":"10.1136\/bmj.g3174","article-title":"Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials","volume":"348","author":"Ford","year":"2014","journal-title":"BMJ"},{"key":"R13-8-20240907","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1111\/j.1365-2036.2009.04105.x","article-title":"Review article: Helicobacter pylori-negative duodenal ulcer disease","volume":"30","author":"Gisbert","year":"2009","journal-title":"Aliment Pharmacol Ther"},{"key":"R14-8-20240907","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1080\/00365520310004696","article-title":"Helicobacter pylori, non-steroidal anti-inflammatory drugs and smoking in risk pattern of gastroduodenal ulcers","volume":"38","author":"Konturek","year":"2003","journal-title":"Scand J Gastroenterol"},{"key":"R15-8-20240907","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1111\/j.1365-2036.2010.04472.x","article-title":"There is an association between selective serotonin reuptake inhibitor use and uncomplicated peptic ulcers: a population-based case-control study","volume":"32","author":"Dall","year":"2010","journal-title":"Aliment Pharmacol Ther"},{"key":"R16-8-20240907","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/s00134-015-3725-1","article-title":"Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients","volume":"41","author":"Krag","year":"2015","journal-title":"Intensive Care Med"},{"key":"R17-8-20240907","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1097\/00004836-199701000-00002","article-title":"Meta-analysis of risk factors for peptic ulcer. Nonsteroidal antiinflammatory drugs, Helicobacter pylori, and smoking","volume":"24","author":"Kurata","year":"1997","journal-title":"J Clin Gastroenterol"},{"key":"R18-8-20240907","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/288373a0","article-title":"The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine","volume":"288","author":"Furchgott","year":"1980","journal-title":"Nature"},{"key":"R19-8-20240907","first-page":"241","article-title":"The role of oxidative stress in acetylcholine-induced relaxation of endothelium-denuded arteries","volume":"64","author":"Cacanyiova","year":"2013","journal-title":"J Physiol Pharmacol"},{"key":"R20-8-20240907","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1139\/y94-188","article-title":"Nitric oxide synthase induction and cytoprotection of rat gastric mucosa from injury by ethanol","volume":"72","author":"Tepperman","year":"1994","journal-title":"Can J Physiol Pharmacol"},{"key":"R21-8-20240907","doi-asserted-by":"crossref","first-page":"57","DOI":"10.2174\/1389557013407160","article-title":"Nitric oxide-releasing nonsteroidal anti-inflammatory drugs: novel gastrointestinal-sparing drugs","volume":"1","author":"Bandarage","year":"2001","journal-title":"Mini Rev Med Chem"},{"key":"R22-8-20240907","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.mehy.2012.11.025","article-title":"Dietary nitrate and reductive polyphenols may potentiate the vascular benefit and alleviate the ulcerative risk of low-dose aspirin","volume":"80","author":"McCarty","year":"2013","journal-title":"Med Hypotheses"},{"key":"R23-8-20240907","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1046\/j.1440-1681.2002.03607.x","article-title":"L-arginine protects against stress-induced gastric mucosal lesions by preserving gastric mucus","volume":"29","author":"Ohta","year":"2002","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"R24-8-20240907","first-page":"G509","article-title":"Gastric alkaline response to mucosa-damaging agents: effect of 16,16-dimethyl prostaglandin E2","volume":"241","author":"Swierczek","year":"1981","journal-title":"Am J Physiol"},{"key":"R25-8-20240907","first-page":"G842","article-title":"Endogenous prostaglandins in gastric alkaline response in the rat stomach after damage","volume":"250","author":"Takeuchi","year":"1986","journal-title":"Am J Physiol"},{"key":"R26-8-20240907","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1007\/BF01296714","article-title":"Irritative and protective activity of mild irritants in rat stomach","volume":"32","author":"Takeuchi","year":"1987","journal-title":"Dig Dis Sci"},{"key":"R27-8-20240907","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1007\/BF02064993","article-title":"Mechanism of gastric alkaline response in the stomach after damage. Roles of nitric oxide and prostaglandins","volume":"40","author":"Takeuchi","year":"1995","journal-title":"Dig Dis Sci"},{"key":"R28-8-20240907","doi-asserted-by":"crossref","first-page":"7240","DOI":"10.1073\/pnas.90.15.7240","article-title":"Nitric oxide activates cyclooxygenase enzymes","volume":"90","author":"Salvemini","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R29-8-20240907","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1007\/BF01317090","article-title":"Possible role of endogenous prostaglandins in alkaline response in rat gastric mucosa damaged by hypertonic NaCl","volume":"29","author":"Nobuhara","year":"1984","journal-title":"Dig Dis Sci"},{"key":"R30-8-20240907","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/j.1472-8206.2004.00203.x","article-title":"Trends in peptic ulcer pharmacotherapy","volume":"18","author":"Sivri","year":"2004","journal-title":"Fundam Clin Pharmacol"},{"key":"R31-8-20240907","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/sj.bjp.0706361","article-title":"Sildenafil prevents indomethacin-induced gastropathy in rats: role of leukocyte adherence and gastric blood flow","volume":"146","author":"Santos","year":"2005","journal-title":"Br J Pharmacol"},{"key":"R32-8-20240907","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1096\/fasebj.10.7.8635690","article-title":"The cellular and molecular basis of gastric mucosal defense","volume":"10","author":"Wallace","year":"1996","journal-title":"FASEB J"},{"key":"R33-8-20240907","doi-asserted-by":"crossref","first-page":"G718","DOI":"10.1152\/ajpgi.00435.2006","article-title":"Dietary nitrate increases gastric mucosal blood flow and mucosal defense","volume":"292","author":"Petersson","year":"2007","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"R34-8-20240907","first-page":"276","article-title":"The potential therapeutic effect of nitric oxide modulators in experimentally-induced gastric ulcers","volume":"4","author":"El-Demerdash","year":"2010","journal-title":"Drug Discov Ther"},{"key":"R35-8-20240907","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jep.2014.10.005","article-title":"Dynamic analysis of the endogenous metabolites in depressed patients treated with TCM formula Xiaoyaosan using urinary (1)H NMR-based metabolomics","volume":"158","author":"Tian","year":"2014","journal-title":"J Ethnopharmacol"},{"key":"R37-8-20240907","first-page":"109","article-title":"Nitric oxide: physiology, pathophysiology, and pharmacology","volume":"43","author":"Moncada","year":"1991","journal-title":"Pharmacol Rev"},{"key":"R38-8-20240907","doi-asserted-by":"crossref","first-page":"E58","DOI":"10.1161\/01.RES.0000012569.55432.02","article-title":"Effects of angiotensin II infusion on the expression and function of NAD(P)H oxidase and components of nitric oxide\/cGMP signaling","volume":"90","author":"Mollnau","year":"2002","journal-title":"Circul Res"},{"key":"R39-8-20240907","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.3390\/nu11081929","article-title":"Imbalance of pro- and anti-angiogenic factors due to maternal vitamin D deficiency causes renal microvasculature alterations affecting the adult kidney function","volume":"11","author":"Ferreira de Almeida","year":"2019","journal-title":"Nutrients"},{"key":"R40-8-20240907","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1007\/BF02090210","article-title":"Protection against gastric ischemia-reperfusion injury by nitric oxide generators","volume":"39","author":"Andrews","year":"1994","journal-title":"Dig Dis Sci"},{"key":"R41-8-20240907","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1172\/JCI115929","article-title":"Nitric oxide, an endothelial cell relaxation factor, inhibits neutrophil superoxide anion production via a direct action on the NADPH oxidase","volume":"90","author":"Clancy","year":"1992","journal-title":"J Clin Invest"},{"key":"R42-8-20240907","first-page":"47","article-title":"Ischemia-reperfusion injury: role of oxygen-derived free radicals","volume":"548","author":"Granger","year":"1986","journal-title":"Acta Physiol Scand Suppl"},{"key":"R43-8-20240907","first-page":"G470","article-title":"Role of oxygen-derived free radicals in indomethacin-induced gastric injury","volume":"261","author":"Vaananen","year":"1991","journal-title":"Am J Physiol"},{"key":"R44-8-20240907","doi-asserted-by":"crossref","first-page":"4651","DOI":"10.1073\/pnas.88.11.4651","article-title":"Nitric oxide: an endogenous modulator of leukocyte adhesion","volume":"88","author":"Kubes","year":"1991","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R45-8-20240907","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/0016-5085(94)90229-1","article-title":"Inhibition of endothelial-derived nitric oxide promotes P-selectin expression and actions in the rat microcirculation","volume":"107","author":"Davenpeck","year":"1994","journal-title":"Gastroenterology"},{"key":"R46-8-20240907","doi-asserted-by":"crossref","first-page":"5193","DOI":"10.1073\/pnas.87.13.5193","article-title":"An L-arginine\/nitric oxide pathway present in human platelets regulates aggregation","volume":"87","author":"Radomski","year":"1990","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R47-8-20240907","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/S0140-6736(87)91481-4","article-title":"Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium","volume":"2","author":"Radomski","year":"1987","journal-title":"Lancet"},{"key":"R48-8-20240907","doi-asserted-by":"crossref","first-page":"3767","DOI":"10.4049\/jimmunol.151.7.3767","article-title":"Modulation of rat mast cell reactivity by IL-1 beta. Divergent effects on nitric oxide and platelet-activating factor release","volume":"151","author":"Hogaboam","year":"1993","journal-title":"J Immunol"},{"key":"R49-8-20240907","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1016\/S0016-5085(96)70014-8","article-title":"Helicobacter pylori stimulates inducible nitric oxide synthase expression and activity in a murine macrophage cell line","volume":"111","author":"Wilson","year":"1996","journal-title":"Gastroenterology"}],"container-title":["Medical Gas Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/2045-9912.310059","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T15:41:40Z","timestamp":1787845300000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/2045-9912.310059"}},"subtitle":["a narrative review"],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.4103\/2045-9912.310059","relation":{},"ISSN":["2045-9912"],"issn-type":[{"value":"2045-9912","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1]]}}}