{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:11:06Z","timestamp":1789582266437,"version":"build-2803163510"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:00:00Z","timestamp":1770508800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":19,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2024ZD0522301"],"award-info":[{"award-number":["2024ZD0522301"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFF0902004"],"award-info":[{"award-number":["2022YFF0902004"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Serum pepsinogen (PG) levels are recognized biomarkers influenced by various factors, including lifestyle,\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    (\n                    <jats:italic>H. pylori<\/jats:italic>\n                    ) infection status, and the presence of gastric mucosal lesions. However, whether baseline serum PG levels exhibit regional heterogeneity independent of concurrent gastric mucosal lesions has not been clearly established. The study aims to investigate the variability of baseline serum PG levels and identify potential influencing factors across China. Data were collected from individuals undergoing routine health checkups at twelve collaborating medical centers across China between October 2016 and October 2021. Serum pepsinogen I (PGI) and pepsinogen II (PGII) were measured and the pepsinogen I\/II ratio (PGR) was calculated; gastroscopy with histopathology was performed to define gastric mucosal status. Detection of\n                    <jats:italic>H. pylori<\/jats:italic>\n                    infection status was performed using histology, serology, and\/or breath tests. Lifestyle factors were obtained via standardized questionnaires. Regional differences and associated factors were evaluated using t-tests\/ANOVA and multivariable linear regression (Stata 18). A total of 2902 individuals were included in the study. Of them, 2382 was classified as non-atrophic gastritis (NAG), and their regional distribution varied. Baseline serum PG levels significantly varied by regions, except between Southern and Central China. Factors such as\n                    <jats:italic>H. pylori<\/jats:italic>\n                    -positive (including prior eradication), high salt intake, and frequent fruit consumption were significantly associated with baseline serum PGR levels nationwide, with \u03b2 value (95%CI) being \u2212\u20092.75 (-3.33, -2.17), 1.66 (0.89, 2.44), and \u2212\u20092.14 (-2.78, -1.51), respectively. Further analysis stratified by\n                    <jats:italic>H. pylori<\/jats:italic>\n                    infection status showed that both high salt and frequent fruit intake remained significantly associated with PGR. Baseline serum PG levels, independent of gastric mucosal lesions, exhibit significant regional variations across China. These variations are primarily associated with\n                    <jats:italic>H. pylori<\/jats:italic>\n                    infection status and dietary factors. Our findings suggest that region-specific and\n                    <jats:italic>H. pylori<\/jats:italic>\n                    -stratified PG cut-off values may be warranted for gastric cancer (GC) screening, pending prospective validation.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-38326-9","type":"journal-article","created":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T15:23:04Z","timestamp":1770564184000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Regional variations in serum pepsinogen levels and their influencing factors: a multi-center cross-sectional study"],"prefix":"10.1038","volume":"16","author":[{"given":"Huang","family":"Jiaojiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Jiaying","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Yuling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,8]]},"reference":[{"issue":"1","key":"38326_CR1","doi-asserted-by":"publisher","first-page":"e2032542","DOI":"10.1001\/jamanetworkopen.2020.32542","volume":"4","author":"CK Noh","year":"2021","unstructured":"Noh, C. K. et al. Association of intensive endoscopic screening burden with gastric cancer detection. JAMA Netw. Open. 4 (1), e2032542 (2021).","journal-title":"JAMA Netw. Open."},{"issue":"9","key":"38326_CR2","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1002\/cncr.32753","volume":"126","author":"YS Suh","year":"2020","unstructured":"Suh, Y. S. et al. National cancer screening program for gastric cancer in korea: nationwide treatment benefit and cost. Cancer 126 (9), 1929\u20131939 (2020).","journal-title":"Cancer"},{"issue":"3","key":"38326_CR3","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1016\/j.cgh.2019.07.045","volume":"18","author":"AP Thrift","year":"2020","unstructured":"Thrift, A. P. & El-Serag, H. B. Burden of gastric cancer. Clin. Gastroenterol. Hepatol. 18 (3), 534\u2013542 (2020).","journal-title":"Clin. Gastroenterol. Hepatol."},{"issue":"6","key":"38326_CR4","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1002\/ijc.34264","volume":"152","author":"J Xi","year":"2023","unstructured":"Xi, J., Li, Y., Zhang, H. & Bai, Z. Dynamic variations of the gastric microbiota: key therapeutic points in the reversal of correa\u2019s cascade. Int. J. Cancer. 152 (6), 1069\u20131084 (2023).","journal-title":"Int. J. Cancer"},{"issue":"2","key":"38326_CR5","doi-asserted-by":"publisher","first-page":"168","DOI":"10.21147\/j.issn.1000-9604.2021.02.05","volume":"33","author":"X Fan","year":"2021","unstructured":"Fan, X. et al. Screening for gastric cancer in china: Advances, challenges and visions. Chin. J. Cancer Res. 33 (2), 168\u2013180 (2021).","journal-title":"Chin. J. Cancer Res."},{"issue":"1","key":"38326_CR6","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1007\/s10120-018-0844-8","volume":"22","author":"B Gantuya","year":"2019","unstructured":"Gantuya, B. et al. Evaluation of serum markers for gastric cancer and its precursor diseases among high incidence and mortality rate of gastric cancer area. Gastric Cancer. 22 (1), 104\u2013112 (2019).","journal-title":"Gastric Cancer"},{"issue":"1","key":"38326_CR7","doi-asserted-by":"publisher","first-page":"4202","DOI":"10.1038\/s41598-022-07947-1","volume":"12","author":"H Kishikawa","year":"2022","unstructured":"Kishikawa, H. et al. Relevance of pepsinogen, gastrin, and endoscopic atrophy in the diagnosis of autoimmune gastritis. Sci. Rep. 12 (1), 4202 (2022).","journal-title":"Sci. Rep."},{"issue":"48","key":"38326_CR8","first-page":"6562","volume":"13","author":"LP Sun","year":"2007","unstructured":"Sun, L. P., Gong, Y. H., Wang, L. & Yuan, Y. Serum pepsinogen levels and their influencing factors: a population-based study in 6990 Chinese from North China. World J. Gastroenterol. 13 (48), 6562\u20136567 (2007).","journal-title":"World J. 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Correlation of ratio of serum pepsinogen I and II with prevalence of gastric cancer and adenoma in Japanese subjects. Am. J. Gastroenterol. 93 (7), 1090\u20131096 (1998).","journal-title":"Am. J. Gastroenterol."},{"issue":"1","key":"38326_CR12","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s12876-017-0641-6","volume":"17","author":"Y Tong","year":"2017","unstructured":"Tong, Y., Wu, Y., Song, Z., Yu, Y. & Yu, X. The potential value of serum pepsinogen for the diagnosis of atrophic gastritis among the health check-up populations in china: a diagnostic clinical research. BMC Gastroenterol. 17 (1), 88 (2017).","journal-title":"BMC Gastroenterol."},{"issue":"2","key":"38326_CR13","doi-asserted-by":"publisher","first-page":"e13065","DOI":"10.1111\/hel.13065","volume":"29","author":"ST Wang","year":"2024","unstructured":"Wang, S. T., Yang, H. W., Zhang, W. L., Li, Z. & Ji, R. 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All participants signed an informed consent form in accordance with the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"7773"}}