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. 2020 Jun 11;10:9472. doi: 10.1038/s41598-020-66295-0

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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VNS improves systemic inflammation and decreased expression level of cytokines and chemokines in plasma. (a) VNS alone downregulates the cytokines evaluated. It also suppresses most of the cytokines upregulated by cisplatin injection (raw data in Supplementary Fig. 1). Clustering is performed to generate a heatmap using clustering software (n = 6–9). (b) CCL2 (CCL2: 368.9 ± 34.2 and 282.0 ± 36.6 pg/ml for Cis-sham and Cis-VNS, respectively; n = 6–9; P = 0.0325). (c) CCL11 (CCL11: 2565.5 ± 210.3 and 1559.1 ± 110.3 pg/ml for Cis-sham and Cis-VNS, respectively; n = 6–9; P < 0.0001). (d) G-CSF (G-CSF: 1010.4 ± 147.5 and 355.4 ± 66.4 pg/ml for Cis-sham and Cis-VNS, respectively; n = 6–9; P = 0.0002). (e) IL-12(p40) (IL-12(p40): 1277.4 ± 85.2 and 777.2 ± 125.9 pg/ml for Cis-sham and Cis-VNS, respectively; n = 6–9; P = 0.0008). Data are expressed as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 (two-way analysis of variance followed by the Sidak post-hoc test). VNS, vagus nerve stimulation; Cis, cisplatin; SEM, standard error of the mean.