{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:26:39Z","timestamp":1787030799725,"version":"build-2736575974"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background and objective<\/jats:title>\n                    <jats:p>Ischemic stroke (IS) is a leading global cause of disability and mortality, characterized by cerebral hypoxia and tissue necrosis. GTP cyclohydrolase 1 (GCH1) regulates endothelial function and oxidative stress; however, whether circulating GCH1 concentrations are altered in acute ischemic stroke (AIS) remains unclear. This exploratory case\u2013control study aimed to investigate plasma GCH1 levels and their associations with clinical characteristics in patients with AIS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Seventy-one patients with AIS and 92 controls undergoing routine health examinations were recruited at the Affiliated Hospital of Youjiang Medical University for Nationalities (January 2024\u2013May 2025). Clinical and biochemical data including lipid profiles, C-reactive protein, homocysteine, and National Institutes of Health Stroke Scale (NIHSS) scores (only for patients with AIS) were collected. Plasma GCH1 levels were measured using an enzyme-linked immunosorbent assay. Statistical analyses were performed to evaluate differences between groups and to examine the associations between plasma GCH1 levels and clinical characteristics. Receiver operating characteristic curve analysis was conducted to assess the discriminatory performance of circulating GCH1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Plasma GCH1 concentrations were significantly lower in AIS patients (6.51\u202f\u00b1\u202f3.59\u202fng\/mL vs. 14.32\u202f\u00b1\u202f3.29\u202fng\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). Binary logistic regression analysis showed that lower plasma GCH1 levels were independently associated with AIS (OR\u202f=\u202f0.496, 95% CI: 0.385\u20130.644,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001), while multiple linear regression analysis demonstrated that AIS was independently associated with lower plasma GCH1 levels (\n                      <jats:italic>B<\/jats:italic>\n                      \u202f=\u202f\u22127.687, 95% CI: \u22129.011 to \u22126.362,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). Plasma GCH1 showed strong discrimination between the two groups (AUC\u202f=\u202f0.924, 95% CI: 0.871\u20130.978) but was not associated with NIHSS scores (Spearman\u2019s rho\u202f=\u202f\u22120.034,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.778).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Plasma GCH1 concentrations were lower in patients with AIS than in health-examination controls and showed high apparent discrimination in this dataset. Because GCH1 was measured after stroke onset and the sample-derived threshold was derived in the same case\u2013control sample, these findings do not establish temporality, causality, or clinical diagnostic utility. Prospective multicenter studies including clinically relevant disease controls and independent external validation are required.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1842462","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:28:33Z","timestamp":1787027313000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between circulating GTP cyclohydrolase 1 concentrations and acute ischemic stroke: an exploratory case\u2013control study in a Chinese population"],"prefix":"10.3389","volume":"17","author":[{"given":"Shengshan","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Neurology, Affiliated Hospital of Youjiang Medical University for Nationalities","place":["Baise, Guangxi, China"]},{"name":"School of Bioscience, Faculty of Pharmacy and Biomedical Sciences, MAHSA University","place":["Selangor, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yang","sequence":"additional","affiliation":[{"name":"Baise Key Laboratory of In Vitro Diagnostic Technology","place":["Baise, Guangxi, China"]},{"name":"Guangxi Key Laboratory of Artificial Intelligence for Genetic Diseases of Long-dwelling Nationalities","place":["Baise, Guangxi, China"]},{"name":"Engineering Research Center of Guangxi Higher Education Institutions for Precise Genetic Testing of Long-dwelling Nationalities","place":["Baise, Guangxi, China"]},{"name":"Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi of Guangxi Higher Education Institutions","place":["Baise, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phaik Har","family":"Yong","sequence":"additional","affiliation":[{"name":"School of Bioscience, Faculty of Pharmacy and Biomedical Sciences, MAHSA University","place":["Selangor, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi Xiang","family":"Ng","sequence":"additional","affiliation":[{"name":"School of Biological and Environmental Sciences, Faculty of Science and Engineering, University of Nottingham Malaysia","place":["Selangor, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoyan","family":"Ren","sequence":"additional","affiliation":[{"name":"Baise Key Laboratory of In Vitro Diagnostic Technology","place":["Baise, Guangxi, China"]},{"name":"Guangxi Key Laboratory of Artificial Intelligence for Genetic Diseases of Long-dwelling Nationalities","place":["Baise, Guangxi, China"]},{"name":"Engineering Research Center of Guangxi Higher Education Institutions for Precise Genetic Testing of Long-dwelling Nationalities","place":["Baise, Guangxi, China"]},{"name":"Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi of Guangxi Higher Education Institutions","place":["Baise, Guangxi, China"]},{"name":"Yaneng BlOscience (Shenzhen) Corporation","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Genome Center, Guangxi KingMed Diagnostics","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guijiang","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Neurology, Affiliated Hospital of Youjiang Medical University for Nationalities","place":["Baise, Guangxi, China"]},{"name":"Baise Key Laboratory of In Vitro Diagnostic Technology","place":["Baise, Guangxi, China"]},{"name":"Guangxi Key Laboratory of Artificial Intelligence for Genetic Diseases of Long-dwelling Nationalities","place":["Baise, Guangxi, China"]},{"name":"Engineering Research Center of Guangxi Higher Education Institutions for Precise Genetic Testing of Long-dwelling Nationalities","place":["Baise, Guangxi, China"]},{"name":"Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi of Guangxi Higher Education Institutions","place":["Baise, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Affiliated Hospital of Youjiang Medical University for Nationalities","place":["Baise, Guangxi, China"]},{"name":"Baise Key Laboratory of In Vitro Diagnostic Technology","place":["Baise, Guangxi, China"]},{"name":"Guangxi Key Laboratory of Artificial Intelligence for Genetic Diseases of Long-dwelling Nationalities","place":["Baise, Guangxi, China"]},{"name":"Engineering Research Center of Guangxi Higher Education Institutions for Precise Genetic Testing of Long-dwelling Nationalities","place":["Baise, Guangxi, China"]},{"name":"Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi of Guangxi Higher Education Institutions","place":["Baise, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1177\/17474930241308142","article-title":"World stroke organization: global stroke fact sheet 2025","volume":"20","author":"Feigin","year":"2025","journal-title":"Int J Stroke"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2820","DOI":"10.1016\/s0140-6736(24)00642-1","article-title":"Stroke","volume":"403","author":"Hilkens","year":"2024","journal-title":"Lancet"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1136\/svn-2021-001374","article-title":"China stroke statistics: an update on the 2019 report from the National Center for healthcare quality Management in Neurological Diseases, China National Clinical Research Center for 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