Journal of Traditional Chinese Medicine ›› 2024, Vol. 44 ›› Issue (5): 1017-1023.DOI: 10.19852/j.cnki.jtcm.20240828.007
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Relative exchangeable copper, a high-quality biomarker for differentiation of Traditional Chinese Medicine syndrome in Wilson’s disease
DING Yufeng1, YANG Wenming1(
), CHENG Yuan1, YANG Yulong1, ZHU Jun2, LU Yachun2, FANG Xiang1, ZHANG Jing1()
- 1 Department of Neurology, the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, China
2 Department of clinical laboratory, the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, China
-
Received:2023-06-11Accepted:2023-11-27Online:2024-10-15Published:2024-09-11 -
Contact:YANG Wenming, Department of Neurology, the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, China. yangwm8810@126.com;ZHANG Jing, Department of Neurology, the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, China. zj5125115@163.com Telephone: +86-551-62838522; +86-15357950670 -
Supported by:Research on the Neuroprotective Mechanism of the Gandouling based on the Regulation of Long Non-coding Ribonucleic Acid Maternally Expressed Gene 3 and Targets Gene Forkhead Box O1 through the Way of Autophagy in Wilson Disease(82104783);Study on Mechanism of Xin’an Medical Gubenpeiyuan Prescription Treating Wilson’s Disease based on Enterohepatic Axis and Enterobrain Axis Pathway(U22A20366);2019 Project of Building Evidence based Practice Capacity for Traditional Chinese Medicine(2019XZZX-NB001);Mechanism Study on the Regulation of Peroxisome Proliferator-activated Receptor-gamma Coactivator-1alpha/Sirtuin-3/Mitochondrial Axis to Maintain Hippocampal Synaptic Homeostasis to Improve Cognitive Impairment in Wilson’s Disease by Qingre Lidan JieDu Prescription(2008085MH264);Mitofusin 2 Mediates the Role of Endoplasmic Reticulum-MAMs-mitochondria Regulation of Synaptic Homeostasis in Wilson’s Disease Neurons and the Mechanism of Qingre Lidan Jiedu Prescription Intervention(2208085MH271)
Cite this article
DING Yufeng, YANG Wenming, CHENG Yuan, YANG Yulong, ZHU Jun, LU Yachun, FANG Xiang, ZHANG Jing. Relative exchangeable copper, a high-quality biomarker for differentiation of Traditional Chinese Medicine syndrome in Wilson’s disease[J]. Journal of Traditional Chinese Medicine, 2024, 44(5): 1017-1023.
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Table 1 Characteristics of the study population
| Item | WD group (n = 78) | N-WD group (n = 32) | HC group (n = 37) |
|---|---|---|---|
| Age (years) | 24±8 | 22±8 | 24±7 |
| Female [n (%)] | 32 (41.03) | 14 (43.75) | 20 (54.05) |
| Time since first symptoms (months) | 14±8 | 8±7 | -- |
| Neurologic symptoms at diagnosis [n (%)] | 54 (69.23) | -- | -- |
| Kayser-Fleischer corneal rings [n (%)] | 73 (93.59) | -- | 0 (0.00) |
| Serum ceruloplasmin (< 200 mg/L) | 77 (98.72) | 5 (15.63) | 12 (32.43) |
| Dominant mutations [n (%)] | |||
| c.2333G>T (R778L, exon 8) | 24 (30.77) | -- | 14 (37.84) |
| c.2975C>T (P992L, exon 13) | 11 (14.10) | -- | 6 (16.22) |
| c.2621C>T (A874V, exon 11) | 6 (7.69) | -- | 3 (8.11) |
Table 1 Characteristics of the study population
| Item | WD group (n = 78) | N-WD group (n = 32) | HC group (n = 37) |
|---|---|---|---|
| Age (years) | 24±8 | 22±8 | 24±7 |
| Female [n (%)] | 32 (41.03) | 14 (43.75) | 20 (54.05) |
| Time since first symptoms (months) | 14±8 | 8±7 | -- |
| Neurologic symptoms at diagnosis [n (%)] | 54 (69.23) | -- | -- |
| Kayser-Fleischer corneal rings [n (%)] | 73 (93.59) | -- | 0 (0.00) |
| Serum ceruloplasmin (< 200 mg/L) | 77 (98.72) | 5 (15.63) | 12 (32.43) |
| Dominant mutations [n (%)] | |||
| c.2333G>T (R778L, exon 8) | 24 (30.77) | -- | 14 (37.84) |
| c.2975C>T (P992L, exon 13) | 11 (14.10) | -- | 6 (16.22) |
| c.2621C>T (A874V, exon 11) | 6 (7.69) | -- | 3 (8.11) |
Figure 1 Comparison of the REC ratios and serum Cp levels in WD, non-Wilsonian liver diseases, and heterozygous ATP7B carriers A: comparison of the serum copper levels in WD, non-Wilsonian liver diseases, and heterozygous ATP7B carriers. B: comparison of the REC ratios in WD, non-Wilsonian liver diseases, and heterozygous ATP7B carriers. WD group (n = 78), N-WD group (n = 32), HC group (n = 37). WD: Wilson’s disease; N-WD: non-Wilsonian liver diseases; HC: heterozygous ATP7B carriers; REC: relative exchangeable copper; Cp: ceruloplasmin. Data are presented as the mean ± standard deviation using one-way analysis of variance.
Figure 1 Comparison of the REC ratios and serum Cp levels in WD, non-Wilsonian liver diseases, and heterozygous ATP7B carriers A: comparison of the serum copper levels in WD, non-Wilsonian liver diseases, and heterozygous ATP7B carriers. B: comparison of the REC ratios in WD, non-Wilsonian liver diseases, and heterozygous ATP7B carriers. WD group (n = 78), N-WD group (n = 32), HC group (n = 37). WD: Wilson’s disease; N-WD: non-Wilsonian liver diseases; HC: heterozygous ATP7B carriers; REC: relative exchangeable copper; Cp: ceruloplasmin. Data are presented as the mean ± standard deviation using one-way analysis of variance.
Figure 2 Comparison of the REC ratios in different ATP7B mutational sites in WD R778L/R778L (n = 5), R778L/R992L (n = 16), and A874V/ R778L (n = 4). REC: relative exchangeable copper; WD: Wilson’s disease. Data are presented as the mean ± standard deviation using one-way analysis of variance.
Figure 2 Comparison of the REC ratios in different ATP7B mutational sites in WD R778L/R778L (n = 5), R778L/R992L (n = 16), and A874V/ R778L (n = 4). REC: relative exchangeable copper; WD: Wilson’s disease. Data are presented as the mean ± standard deviation using one-way analysis of variance.
Figure 3 Comparison of the REC ratios in different TCM syndromes D-HIA group (n = 24), P-SCS group (n = 28), L-KYD group (n = 26). REC: relative exchangeable copper; TCM: Traditional Chinese Medicine; D-HIA: Dampness-heat internal accumulation syndrome; P-SCS: Phlegm-stasis combination syndrome; L-KYD: Liver-kidney Yin deficiency syndrome. Data are presented as the mean ± standard deviation using one-way analysis of variance.
Figure 3 Comparison of the REC ratios in different TCM syndromes D-HIA group (n = 24), P-SCS group (n = 28), L-KYD group (n = 26). REC: relative exchangeable copper; TCM: Traditional Chinese Medicine; D-HIA: Dampness-heat internal accumulation syndrome; P-SCS: Phlegm-stasis combination syndrome; L-KYD: Liver-kidney Yin deficiency syndrome. Data are presented as the mean ± standard deviation using one-way analysis of variance.
Table 2 FC value in all subregions of the lenticular nucleus among different TCM syndromes
| Subregion | D-HIA group (n = 17) | P-SCS group (n = 23) | L-KYD group (n = 18) |
|---|---|---|---|
| Left PUT-VA | 0.27±0.11 | 0.14±0.07 | 0.06±0.10 |
| Left PUT-DA | 0.26±0.09 | 0.15±0.04 | 0.05±0.08 |
| Left PUT-DP | 0.25±0.09 | 0.15±0.09 | 0.07±0.08 |
| Left PUT-VP | 0.31±0.08 | 0.21±0.04 | 0.09±0.08 |
| Right PUT-VA | 0.22±0.05 | 0.14±0.07 | 0.04±0.10 |
| Right PUT-DA | 0.25±0.07 | 0.15±0.06 | 0.03±0.14 |
| Right PUT-DP | 0.21±0.08 | 0.15±0.10 | 0.08±0.13 |
| Right PUT-VP | 0.28±0.11 | 0.21±0.07 | 0.14±0.09 |
Table 2 FC value in all subregions of the lenticular nucleus among different TCM syndromes
| Subregion | D-HIA group (n = 17) | P-SCS group (n = 23) | L-KYD group (n = 18) |
|---|---|---|---|
| Left PUT-VA | 0.27±0.11 | 0.14±0.07 | 0.06±0.10 |
| Left PUT-DA | 0.26±0.09 | 0.15±0.04 | 0.05±0.08 |
| Left PUT-DP | 0.25±0.09 | 0.15±0.09 | 0.07±0.08 |
| Left PUT-VP | 0.31±0.08 | 0.21±0.04 | 0.09±0.08 |
| Right PUT-VA | 0.22±0.05 | 0.14±0.07 | 0.04±0.10 |
| Right PUT-DA | 0.25±0.07 | 0.15±0.06 | 0.03±0.14 |
| Right PUT-DP | 0.21±0.08 | 0.15±0.10 | 0.08±0.13 |
| Right PUT-VP | 0.28±0.11 | 0.21±0.07 | 0.14±0.09 |
Figure 4 FC value changes in different TCM syndromes A: the seed-based FC map in all Wilson’s disease patients; B: FC value changes of left putamen in different TCM syndromes; C: FC value changes of right putamen in different TCM syndromes. D-HIA Group (n = 17), P-SCS group (n = 23), L-KYD group (n = 18). FC: functional connectivity; TCM: Traditional Chinese Medicine; D-HIA: Dampness-heat internal accumulation syndrome; P-SCS: Phlegm-stasis combination syndrome; L-KYD: Liver-kidney Yin deficiency syndrome; PUT-VA: ventral anterior putamen; PUT-DA: dorsal anterior putamen; PUT-DP: dorsal posterior putamen; PUT-VP: ventral posterior putamen. aP<0.05 vs P-SCS group; bP<0.001 vs L-KYD group, cP<0.05 vs L-KYD group. Data are presented as the mean ± standard deviation using one-way analysis of variance.
Figure 4 FC value changes in different TCM syndromes A: the seed-based FC map in all Wilson’s disease patients; B: FC value changes of left putamen in different TCM syndromes; C: FC value changes of right putamen in different TCM syndromes. D-HIA Group (n = 17), P-SCS group (n = 23), L-KYD group (n = 18). FC: functional connectivity; TCM: Traditional Chinese Medicine; D-HIA: Dampness-heat internal accumulation syndrome; P-SCS: Phlegm-stasis combination syndrome; L-KYD: Liver-kidney Yin deficiency syndrome; PUT-VA: ventral anterior putamen; PUT-DA: dorsal anterior putamen; PUT-DP: dorsal posterior putamen; PUT-VP: ventral posterior putamen. aP<0.05 vs P-SCS group; bP<0.001 vs L-KYD group, cP<0.05 vs L-KYD group. Data are presented as the mean ± standard deviation using one-way analysis of variance.
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