Table of Contents Author Guidelines Submit a Manuscript
Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 235969, 9 pages
http://dx.doi.org/10.1155/2013/235969
Review Article

ZHENG-Omics Application in ZHENG Classification and Treatment: Chinese Personalized Medicine

1Center for Traditional Chinese Medicine and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
2Department of Integrated Oncology, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
3School of Chinese Medicine, Hong Kong Baptist University, Hong Kong

Received 10 January 2013; Revised 22 February 2013; Accepted 27 February 2013

Academic Editor: Zhaoxiang Bian

Copyright © 2013 Jianye Dai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. T. A. Clayton, J. C. Lindon, O. Cloarec et al., “Pharmaco-metabonomic phenotyping and personalized drug treatment,” Nature, vol. 440, no. 7087, pp. 1073–1077, 2006. View at Publisher · View at Google Scholar · View at Scopus
  2. Huangdi's Internal Classic.
  3. J. L. Tang, B. Y. Liu, and K. W. Ma, “Traditional Chinese medicine,” The Lancet, vol. 372, no. 9654, pp. 1938–1940, 2008. View at Publisher · View at Google Scholar
  4. Y. T. He, A. P. Lu, Y. L. Zha, and I. Tsang, “Differential effect on symptoms treated with traditional Chinese medicine and Western combination therapy in RA patients,” Complementary Therapies in Medicine, vol. 16, no. 4, pp. 206–211, 2008. View at Publisher · View at Google Scholar · View at Scopus
  5. C. Lu, Q. I. Zha, A. I. Chang, Y. T. He, and A. P. Lu, “Pattern differentiation in traditional chinese medicine can help define specific indications for biomedical therapy in the treatment of rheumatoid arthritis,” Journal of Alternative and Complementary Medicine, vol. 15, no. 9, pp. 1021–1025, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. M. A. Hamburg and F. S. Collins, “The path to personalized medicine,” The New England Journal of Medicine, vol. 363, no. 4, pp. 301–304, 2011. View at Publisher · View at Google Scholar
  7. J. L. Yuan, H. Zhang, L. Wang et al., “Biochemical characteristics of traditional Chinese medicine syndromes and their elements in patients with hepatitis B cirrhosis,” Journal of Chinese Integrative Medicine, vol. 9, no. 4, pp. 374–381, 2011. View at Publisher · View at Google Scholar
  8. Y. Q. Xie, H. Wang, Y. P. Wu, D. H. Yin, Z. S. Wang, and Y. H. Huang, “Association of APOE polymorphisms and insulin resistance with TCM syndromes in type 2 diabetes patients with macroangiopathy,” Molecular Medicine Reports, vol. 4, no. 6, pp. 1219–1223, 2011. View at Publisher · View at Google Scholar
  9. X. Q. Yue and Q. Liu, “Analysis of studies on pattern recognition of tongue image in traditional Chinese medicine by computer technology,” Journal of Chinese Integrative Medicine, vol. 2, no. 5, pp. 326–329, 2004. View at Publisher · View at Google Scholar
  10. B. Pang, D. Zhang, N. Li, and K. Wang, “Computerized tongue diagnosis based on Bayesian networks,” IEEE Transactions on Biomedical Engineering, vol. 51, pp. 1803–1810, 2004. View at Publisher · View at Google Scholar
  11. Y. Wu, Y. Cun, J. Dong et al., “Polymorphisms in PPARD, PPARG and APM1 associated with four types of traditional Chinese medicine constitutions,” Journal of Genetics and Genomics, vol. 37, no. 6, pp. 371–379, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. H. M. Ni, Y. P. Wu, and Y. M. He, “Differential expression genes in teenagers with kidney-Yang sthenia constitution by genechiptechnique,” Acta Univ Tradit Med Sin Pharm Shanghai, vol. 38, pp. 3–5, 2004 (Chinese). View at Google Scholar
  13. Y. Feng, Z. H. Wu, X. Z. Zhou, Z. M. Zhou, and W. Y. Fan, “Knowledge discovery in traditional Chinese medicine: state of the art and perspectives,” Artificial Intelligence in Medicine, vol. 38, no. 3, pp. 219–236, 2006. View at Publisher · View at Google Scholar
  14. X. C. Liu, H. Liang, Z. Tian, Y. Chen, and L. Zhang, “Comparative proteomic analysis of human kidney-Yang deficiency syndrome serum,” Chinese Journal of Biochemistry and Molecular Biology, vol. 23, no. 7, pp. 592–599, 2007 (Chinese). View at Google Scholar
  15. L. H. Tang, X. D. Wo, D. Z. Lu, M. R. Shi, Y. Li, and L. K. Wo, “Effects of warm and tonify kidney-Yang herbs on liver mitochondria proteome of kidney-Yang deficiency rats,” Chinese Pharmaceutical Journal, vol. 42, no. 3, pp. 169–175, 2007. View at Google Scholar · View at Scopus
  16. P. Wang, H. Sun, H. T. Lv et al., “Thyroxine and reserpine-induced changes in metabolic profiles of rat urine and the therapeutic effect of Liu Wei Di Huang Wan detected by UPLC-HDMS,” Journal of Pharmaceutical and Biomedical Analysis, vol. 53, no. 3, pp. 631–645, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. X. M. Lu, Z. L. Xiong, J. L. Li, S. N. Zheng, T. G. Huo, and F. M. Li, “Metabonomic study on “Kidney-Yang deficiency syndrome” and intervention effects of Rhizoma Drynariae extracts in rats using ultra performance liquid chromatography coupled with mass spectrometry,” Talanta, vol. 83, no. 3, pp. 700–708, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. S. Li, Z. Q. Zhang, L. J. Wu, X. G. Zhang, Y. D. Li, and Y. Y. Wang, “Understanding Zheng in traditional Chinese medicine in the context of neuro-endocrine-immune network,” IET Systems Biology, vol. 1, no. 1, pp. 51–60, 2007. View at Publisher · View at Google Scholar
  19. T. Ma, C. G. Tan, H. Zhang, M. Q. Wang, W. J. Ding, and S. Li, “Bridging the gap between traditional Chinese medicine and systems biology: the connection of Cold syndrome and NEI network,” Molecular BioSystems, vol. 6, no. 4, pp. 613–619, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. S. J. Sun, J. Y. Dai, W. Y. Wang et al., “Metabonomic evaluation of ZHENG differentiation and treatment by Fuzhenghuayu tablet in hepatitis-B-caused cirrhosis,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 453503, 8 pages, 2012. View at Publisher · View at Google Scholar
  21. M. Chen, L. Zhao, and W. Jia, “Metabonomics study on the biochemical profiles of a hydrocortisone-induced animal,” Journal of Proteome Research, vol. 4, no. 6, pp. 2391–2396, 2005. View at Publisher · View at Google Scholar
  22. Y. G. Chu, J. Shi, and Y. H. Hu, “Serum proteomic study on hypertension patients with Gan-Dan damp-heat syndrome,” Chinese Journal of Integrative Medicine, vol. 30, no. 1, pp. 37–41, 2010. View at Google Scholar
  23. Z. Z. Guo, S. H. Yu, Y. Guan et al., “Molecular mechanisms of same TCM syndrome for different diseases and different TCM syndrome for same disease in chronic hepatitis B and liver cirrhosis,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 120350, 9 pages, 2012. View at Publisher · View at Google Scholar
  24. N. J. Zeng, Q. H. Liang, X. G. Xiong et al., “Proteomics analysis and identification on a peripheral blood lymphocyte of Ganyang Huafeng syndrome of cerebral infarction,” Chinese Journal of Information on Traditional Chinese Medicine, vol. 15, no. 4, pp. 11–15, 2008 (Chinese). View at Google Scholar
  25. Q. X. Tan, Z. P. Lu, X. L. Zhong, and X. G. Zhang, “Preliminary study on change of serum proteome in liver stagnation syndrome,” Liaoning Journal of Traditional Chinese Medicine, vol. 33, pp. 157–158, 2006 (Chinese). View at Google Scholar
  26. C. Lu, C. Xiao, L. H. Zhao et al., “Comparison of gene profile of peripheral CD4+ lymphocytes in rheumatoid arthritis with cold and heat syndrome,” Chinese Journal of Basic Medicine in Traditional Chinese Medicine, vol. 12, no. 2, pp. 130–133, 2006 (Chinese). View at Google Scholar
  27. Y. Q. Wang, L. P. Yang, W. J. Ding, H. Gao, and Q. G. Wang, “A report on 15 differential expression genes found in a cold-syndrome genealogy,” Journal of Traditional Chinese Medicine, vol. 47, pp. 131–133, 2006. View at Google Scholar
  28. Y. Gu, C. Lu, Q. L. Cha et al., “Plasma metabonomics study of rheumatoid arthritis and its Chinese medicine subtypes by using liquid chromatography and gas chromatography coupled with mass spectrometry,” Molecular Systems Biology, vol. 8, no. 5, pp. 1535–1543, 2012. View at Google Scholar
  29. C. B. Yang, J. Xue, P. S. Yin, J. S. Zuo, and K. C. Xu, “Expression of blc-2 gene in spleen deficiency syndrome in colorectal carcinoma and the regulatory effect of Jianpikangfu decoction,” Academic Journal of First Military Medical University, vol. 25, pp. 1268–1269, 2005 (Chinese). View at Google Scholar
  30. Z. M. Yang, W. W. Chen, and Y. F. Wang, “Study on gene differential expressions of substance and energy metabolism in chronic superficial gastritis patients of Pi deficiency syndrome and of Pi-Wei hygroyrexia syndrome,” Chinese Journal of Integrative Medicine, vol. 32, no. 9, pp. 1180–1187, 2012. View at Google Scholar
  31. P. Liu, Y. Y. Zhang, and J. Qiao, “Establishment and analysis of serum two-dimensional gel electrophoresis profiles of myasthenia gravis patients with spleen and kidney deficiency syndrome,” Journal of Chinese Integrative Medicine, vol. 5, no. 2, pp. 150–154, 2007. View at Google Scholar · View at Scopus
  32. L. Weng, J. Du, W. T. He, and C. Q. Ling, “Characteristic genomics of peripheral blood mononuclear cells of hepatocellular carcinoma patients with liver-kidney yin deficiency syndrome,” Chinese Journal of Integrative Medicine, vol. 10, no. 4, pp. 406–415, 2012. View at Publisher · View at Google Scholar
  33. H. S. Zheng, J. Jiang, W. Jia et al., “Research on metabolomics in chronic heart failure with kidney-Yang deficiency,” China Journal of Traditional Chinese Medicine and Pharmacy, vol. 25, no. 2, pp. 198–201, 2010 (Chinese). View at Google Scholar
  34. Y. Guan, H. Zhang, W. Zhang, and S. B. Su, “Analysis of differential gene expression profile in peripheral blood of patients with chronic hepatitis B and syndromes of dual deficiency of liver and kidney yin and accumulation of dampness heat,” Chinese Journal of Integrative Medicine, vol. 10, no. 7, pp. 751–756, 2012. View at Publisher · View at Google Scholar
  35. Y. Q. Wang, F. F. Li, W. J. Wang, L. Y. Zhao, L. Guo, and H. F. Wang, “Serum proteomics study of chronic gastritis with dampness syndrome in traditional Chinese medicine,” Journal of Chinese Integrative Medicine, vol. 5, no. 5, pp. 514–516, 2007. View at Publisher · View at Google Scholar · View at Scopus
  36. Q. Wang, H. Y. Xi, and J. H. Gao, “Study on characteristics of peripheral blood gene expression profile in the obesity with phlegm-dampness constitution,” Journal of Traditional Chinese Medicine, vol. 47, pp. 851–858, 2006. View at Google Scholar
  37. X. J. Ma, H. J. Yin, and K. J. Chen, “Differential gene expression profiles in coronary heart disease patients of blood stasis syndrome in traditional Chinese medicine and clinical role of target gene,” Chinese Journal of Integrative Medicine, vol. 15, no. 2, pp. 101–106, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. Z. K. Yuan, X. P. Huang, G. B. Tan et al., “Detective analysis on polymorphism of apolipoprotein E gene in blood-stasis syndrome of coronary heart disease,” Journal of Beijing University of Traditional Chinese Medicine, vol. 31, no. 12, pp. 830–834, 2008 (Chinese). View at Google Scholar
  39. Z. K. Yuan, L. P. Wang, and X. P. Huang, “The screening and the functional pathway analysis of differential genes correlated with coronary heart disease of blood stasis syndrome,” Chinese Journal of Integrative Medicine, vol. 32, no. 10, pp. 1313–1318, 2012. View at Google Scholar
  40. H. J. Wu, Z. C. Ma, Y. Gao, and S. Q. Wang, “Study on GAP in blood-stasis type of coronary heart disease by using proteomic technique,” Chinese Journal of Integrative Medicine on Cardio/Cerebrovascular Disease, vol. 3, pp. 189–191, 2005 (Chinese). View at Google Scholar
  41. J. Wang, Z. F. Li, H. H. Zhao et al., “Characteristics of urine metabonomics in patients with blood stasis syndrome of CHN unstable angina,” Journal of Beijing University of Traditional Chinese Medicine, vol. 35, no. 4, pp. 284–288, 2012. View at Google Scholar
  42. Q. Y. Li, Z. Z. Guo, J. Liang et al., “Interleukin-10 genotype correlated to deficiency syndrome in hepatitis B cirrhosis,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 298925, 6 pages, 2012. View at Publisher · View at Google Scholar
  43. Y. N. Song, H. Zhang, Y. Guan et al., “Classification of traditional Chinese medicine syndromes in patients with chronic hepatitis B by SELDI-based proteinchip analysis,” Based Complementary and Alternative Medicine, vol. 2012, Article ID 626320, 10 pages, 2012. View at Publisher · View at Google Scholar
  44. Q. W. Chen, X. Q. Huang, G. J. Yang et al., “Preliminary study of serum metabonomics on Yang deficiency syndrome of patients with primary liver cancer,” Chinese Archives of Traditional Chinese Medicine, vol. 30, no. 3, pp. 526–529, 2012. View at Google Scholar
  45. T. Wu, M. Yang, H. F. Wei, S. H. He, S. C. Wang, and G. Ji, “Application of metabolomics in traditional Chinese medicine differentiation of deficiency and excess syndromes in patients with diabetes mellitus,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 968083, 11 pages, 2012. View at Publisher · View at Google Scholar
  46. C. H. Yang, J. M. Lin, and J. Xie, “Study on the metabolic difference of hypertension patients of Gan-Yang hyperactivity syndrome and Yin-Yang deficiency syndrome,” Chinese Journal of Integrative Medicine, vol. 32, no. 9, pp. 1204–1207, 2012. View at Google Scholar
  47. L. Weng, J. Du, W. T. He, and C. Q. Ling, “Characteristic genomics of peripheral blood monouclear cells of hepatocellular carcinoma patients with liver-kidney yin deficiency syndrome,” Chinese Journal of Integrative Medicine, vol. 10, no. 4, pp. 406–415, 2012. View at Publisher · View at Google Scholar
  48. H. Q. Jiang, Y. L. Li, and J. Xie, “Urine metabonomic study on hypertension patients of ascendant hyperactivity of Gan Yang syndrome by high performance liquid chromatography coupled with time of flight mass spectrometry,” Chinese Journal of Integrative Medicine, vol. 32, no. 3, pp. 333–337, 2012. View at Google Scholar
  49. J. J. Hu, Z. Q. Chen, G. W. Zhong, W. Li, and T. H. Yin, “Comparative proteomics analysis on splenic lymphocytes in migraine rat model with hyperactivity of liver-yang,” Chinese Journal of Information on Traditional Chinese Medicine, vol. 15, pp. 34–37, 2008 (Chinese). View at Google Scholar
  50. G. W. Zhong, J. Hu, Z. Chen et al., “Effect of the formulae for calming the liver and suppressing YANG on lymphocyte proteome in migraine rats with syndrome of hyperactivity of liver-YANG,” Journal of Central South University (Medical Sciences), vol. 35, no. 1, pp. 70–76, 2010 (Chinese). View at Publisher · View at Google Scholar · View at Scopus
  51. L. Y. Zhou, Z. Q. Chen, and W. Li, “Observation of differential protein of hypothalamus in the hyperthyroidlsm rats with hyperactivity of liver-yang,” Chinese Journal of Information on Traditional Chinese Medicine, vol. 14, pp. 18–20, 2007. View at Google Scholar
  52. X. Zhang, X. Zeng, X. J. Duan, and R. M. Ou, “Reproduction of a rat model of liver-yang hyperactivity syndrome with essential hypertension and analysis of protein expression in liver,” Sichuan Journal of Traditional Chinese Medicine, vol. 26, pp. 9–11, 2008. View at Google Scholar
  53. X. L. Zhong, Z. P. Lu, L. J. Qian, X. H. Liu, Q. X. Tan, and X. G. Zhang, “Differential expression of serum proteome on stagnation on liver-Qi syndrome model rats,” China Journal of Traditional Chinese Medicine and Pharmacy, vol. 21, no. 5, pp. 399–401, 2006. View at Google Scholar
  54. S. Wang, S. J. Zou, X. Y. Chen, and W. J. Gang, “Primary study on changes of gene expression profile in hippocampl of reserpine animal models with spleen-asthenia,” Journal of Integrated Traditional Chinese and Western Medicine, vol. 13, pp. 841–844, 2004. View at Google Scholar
  55. H. G. Luo, J. Ding, G. X. Yue, and J. X. Chen, “Metabonomic study of syndrome of liver Qi stagnation and spleen deficiency in rats,” Journal of Chinese Integrative Medicine, vol. 5, pp. 307–313, 2007. View at Google Scholar
  56. Z. Y. Shen, Y. Chen, J. H. Huang, and Z. W. Hu, “The gene expression profile in hypothalamus-pituitary-adrenal-thymus(HPAT) axis from EF-treated old rats,” Chinese Journal of Immunology, vol. 20, pp. 59–62, 2004 (Chinese). View at Google Scholar
  57. M. J. Chen, L. P. Zhao, and W. Jia, “Metabonomic study on the biochemical profiles of a hydrocortisone-induced animal model,” Journal of Proteome Research, vol. 4, no. 6, pp. 2391–2396, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. J. X. Liu, L. Miao, X. Z. Li, and Y. H. Pan, “Proteomics research of serum of Chinese experimental mini-pig model with syndrome of phlegm and blood stasis of coronary,” Pharmacology and Clinics of Chinese Materia Medica, vol. 26, pp. 73–76, 2010. View at Google Scholar
  59. L. Tong, S. H. Chen, Z. C. Ma, J. Huang, Y. Ding, and S. Q. Wang, “Accessing gene expression profile of blood deficiency mice using hematopoietic-ralated cytokine oligonucleotide microarrays,” Chinese Traditional and Herbal Drugs, vol. 34, no. 7, pp. 625–629, 2003 (Chinese). View at Google Scholar
  60. W. X. Jian, Z. K. Yuan, and X. P. Huang, “Detection and analysis on plasma metabolomics in patient with coronary heart disease of xin-blood stasis syndrome pattern,” Chinese Journal of Integrative Medicine, vol. 30, pp. 579–584, 2010. View at Google Scholar
  61. Y. Wang, Z. F. Li, J. X. Chen et al., “Study of mini-pig serum of coronary heart disease (chronic myocardial ischemia) with syndrome of blood stasis based on nuclear,” Chinese Journal of Analytical Chemistry, vol. 39, no. 8, pp. 1274–1278, 2011 (Chinese). View at Google Scholar
  62. Z. Q. Pan, Z. Q. Fang, W. L. Lu et al., “Difference of gene expression in adrenal gland of H22 tumor mice of Yang-Qi deficiency syndrome and Qi-Yin-Yang deficiency syndrome,” Acta Universitatis Traditionis Medicalis Sinensis Pharmacologiaeque Shanghai, vol. 22, no. 3, pp. 45–50, 2008 (Chinese). View at Google Scholar
  63. C. Lu, C. Xiao, G. Chen et al., “Cold and heat pattern of rheumatoid arthritis in traditional Chinese medicine: distinct molecular signatures indentified by microarray expression profiles in CD4-positive T cell,” Rheumatology International, vol. 32, no. 1, pp. 61–68, 2012. View at Publisher · View at Google Scholar · View at Scopus
  64. Y. Liu, P. Liu, R. Dai et al., “Analysis of plasma proteome from cases of the different traditional Chinese medicine syndromes in patients with chronic hepatitis B,” Journal of Pharmaceutical and Biomedical Analysis, vol. 59, pp. 173–178, 2012. View at Publisher · View at Google Scholar
  65. C. L. Lu, X. Y. Qu, and J. G. Jiang, “Proteomics and syndrome of Chinese medicine,” Journal of Cellular and Molecular Medicine, vol. 14, no. 12, pp. 2721–2728, 2010. View at Publisher · View at Google Scholar
  66. H. van Wietmarschen, K. Yuan, C. Lu et al., “Systems biology guided by Chinese medicine reveals new markers for sub-typing rheumatoid arthritis patients,” Journal of Clinical Rheumatology, vol. 15, no. 7, pp. 330–337, 2009. View at Publisher · View at Google Scholar
  67. P. Sun, G. A. Luo, M. Q. Qiao et al., “Studies on the metabonomics of premenstrual syndrome liver-Qi invasion patient interfered by Jingqianping granules,” World Science and Technology/Modernization of Traditional Chinese Medicine and Materia Medica, vol. 12, no. 2, pp. 195–201, 2010. View at Publisher · View at Google Scholar
  68. Y. Qiu, M. Su, Y. Liu et al., “Application of ethyl chloroformate derivatization for gas chromatography-mass spectrometry based metabonomic profiling,” Analytica Chimica Acta, vol. 583, no. 2, pp. 277–283, 2007. View at Publisher · View at Google Scholar · View at Scopus
  69. Chinese Society of Hepatology and Chinese Medical Association, “The guidelines of prevention and treatment for chronic hepatitis B,” Chinese Journal of Hepatology, vol. 13, pp. 881–891, 2005 (Chinese). View at Google Scholar
  70. Y. X. Zhang and B. H. Wei, “Evaluation criteria of the clinical diagnosis, drug efficacy and TCM syndrome differentiation for cirrhosis (pilot program),” Chinese Journal of Integrative Medicine, vol. 14, pp. 237–238, 1994 (Chinese). View at Google Scholar
  71. J. F. Boulicaut, F. Esposito, F. Giannotti, and D. Pedreschi, Eds., Proceedings of the 8th European Conference on Principles and Practice of Knowledge Discovery in Databases, Springer, Berlin, Germany, 2004.
  72. S. Li, “Computational Systems Biology-based TCM Research: a case study of cold/heat zheng and associated formula,” World Science and Technology/Modernization of Traditional Chinese Medicine and Materia Medica, vol. 9, no. 1, pp. 105–111, 2007. View at Google Scholar
  73. H. L. Wu, X. M. Ruan, and W. J. Luo, “Cluster analysis on TCM syndromes in 319 coronary artery disease patients for establishment of syndrome diagnostic figure,” Chinese Journal of Integrative Medicine, vol. 27, pp. 616–618, 2007. View at Google Scholar
  74. C. T. Shen, H. Q. Zhang, and X. H. Zhu, “Investigation and analysis on diagnostic standard for TCM syndrome differentiation in 400 patients with climacteric syndrome,” Chinese Journal of Integrative Medicine, vol. 24, pp. 517–520, 2004. View at Google Scholar
  75. W. H. Liu, X. Z. Yan, L. Zhang, Q. Zhang, L. H. Wang, and F. H. Yu, “Metabonomics study on phlegm and blood stasis evolution of hyperlipidemia and atherosclerosis,” Liaoning Journal of Traditional Chinese Medicine, vol. 49, no. 5, pp. 738–741, 2008 (Chinese). View at Google Scholar