{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:50:02Z","timestamp":1790704202003,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The drug\u2010refractory epilepsy (DRE) in children is commonly observed but the underlying mechanisms remain elusive. We examined whether fatty acids (FAs) and lipids are potentially associated with the pharmacoresistance to valproic acid (VPA) therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This single\u2010center, retrospective cohort study was conducted using data from pediatric patients collected between May 2019 and December 2019 at the Children's Hospital of Nanjing Medical University. Ninety plasma samples from 53 responders with VPA monotherapy (RE group) and 37 non\u2010responders with VPA polytherapy (NR group) were collected. Non\u2010targeted metabolomics and lipidomics analysis for those plasma samples were performed to compare the potential differences of small metabolites and lipids between the two groups. Plasma metabolites and lipids passing the threshold of variable importance in projection value &gt;1, fold change &gt;1.2 or &lt;0.8, and\n                      <jats:italic>p<\/jats:italic>\n                      \u2010value &lt;0.05 were regarded as statistically different substances.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 204 small metabolites and 433 lipids comprising 16 different lipid subclasses were identified. The well\u2010established partial least squares\u2010discriminant analysis (PLS\u2010DA) revealed a good separation of the RE from the NR group. The FAs and glycerophospholipids status were significantly decreased in the NR group, but their triglycerides (TG) levels were significantly increased. The trend of TG levels in routine laboratory tests was in line with the lipidomics analysis. Meanwhile, cases from the NR group were characterized by a decreased level of citric acid and L\u2010thyroxine, but with an increased level of glucose and 2\u2010oxoglutarate. The\u00a0top\u00a0two enriched metabolic pathways\u00a0involved in the DRE condition\u00a0were\u00a0biosynthesis of unsaturated FAs and linoleic acid metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>The results of this study suggested an association between metabolism of FAs and the medically intractable epilepsy. Such novel findings might propose a potential mechanism linked to the energy metabolism. Ketogenic acid and FAs supplementation might therefore be high\u2010priority strategies for DRE management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.12712","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T03:10:54Z","timestamp":1676862654000},"page":"466-478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Integrating metabolomics and lipidomics revealed a decrease in plasma fatty acids but an increase in triglycerides in children with drug\u2010refractory epilepsy"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6660-8145","authenticated-orcid":false,"given":"Hong\u2010Li","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Sciences Research Center Children's Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0047-4068","authenticated-orcid":false,"given":"Na","family":"Dong","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue\u2010Tao","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao\u2010Ran","family":"Dai","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Hui","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Sciences Research Center Children's Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan\u2010Yuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Sciences Research Center Children's Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Sciences Research Center Children's Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Chun","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Sciences Research Center Children's Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Peng","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurology Children's Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4800-6762","authenticated-orcid":false,"given":"Feng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Sciences Research Center Children's Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac082"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.21037\/tp-21-595"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12092616"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30408-8"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-022-00651-8"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70092-9"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2020.2282"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/nutrit\/nuaa112"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv325"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2012.11.005"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17351"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104061"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2012.11.004"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.01.004"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2018.06.003"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-022-00672-9"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1776"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1039\/b618553n"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2934"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060713-035324"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2009.11.005"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00459"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-51337-z"},{"issue":"11","key":"e_1_2_10_25_1","first-page":"1","article-title":"The effect of omega\u20103 fatty acid supplementation on seizure frequency in individuals with epilepsy: a systematic review and meta\u2010analysis","volume":"25","author":"Sohouli MH","year":"2021","journal-title":"Nutr Neurosci."},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02397.x"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2020.599044"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2020.108198"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac500317c"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09550-x"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13709"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.640371"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2016.07.003"},{"issue":"12","key":"e_1_2_10_34_1","article-title":"A switch to polyunsaturated fatty acid based ketogenic diet improves seizure control in patients with drug\u2010resistant epilepsy on the mixed fat ketogenic diet: a retrospective open label trial","volume":"11","author":"Nathan J","year":"2019","journal-title":"Cureus."},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02654.x"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-008-9027-2"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004704"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12734"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.741244"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2017.08.014"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2021.102271"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1177\/0148607115595980"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-019-01134-z"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.10.065"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1590-18.2018"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharep.2016.09.001"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0120424"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2012.11.017"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI79727"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00513"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.07.012"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181ab2b11"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2020.106992"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2013.05.012"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2020.106428"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14554"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16745"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12123870"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-020-01731-w"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2020.106299"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-020-01729-4"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0341-16.2017"},{"issue":"1","key":"e_1_2_10_63_1","first-page":"65","article-title":"Metabolic profiling of the cerebrospinal fluid in pediatric epilepsy","volume":"74","author":"Akiyama T","year":"2020","journal-title":"Acta Med Okayama."},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2015.07.021"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-010-0339-4"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23247"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201500182"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22895"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.44702"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.11.069"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.12712","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/epi4.12712","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.12712","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T00:58:32Z","timestamp":1692493112000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.12712"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3]]},"references-count":69,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/epi4.12712"],"URL":"https:\/\/doi.org\/10.1002\/epi4.12712","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"value":"2470-9239","type":"print"},{"value":"2470-9239","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3]]},"assertion":[{"value":"2022-10-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}