Journal of Traditional Chinese Medicine ›› 2026, Vol. 46 ›› Issue (1): 183-194.DOI: 10.19852/j.cnki.jtcm.2026.01.017
• Original Articles • Previous Articles Next Articles
Multi-omics-based study on the biological characteristics of kidney renal deficiency and blood stasis in ankylosing spondylitis
GONG Yifan1, XU Xiaohan2, MA Jie4, PANG Bo2, LIU Wanlin4, LIU Hongxiao1(
)
- 1 Department of Rheumatology, Guang 'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
2 Department of Rheumatology, Guang'anmen Hospital Jinan, China Academy of Chinese Medical Sciences, Jinan 250012, China
3 Department of Clinical Laboratory, Guang 'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
4 Beijing Proteomics Research Center, Beijing 100094, China
-
Received:2024-12-12Accepted:2025-03-07Online:2026-02-15Published:2026-01-28 -
Contact:LIU Hongxiao, Department of Rheumatology, Guang 'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.liuhongxiao_123@163.com ;Telephone: +86-15600219273 -
About author:GONG Yifan andXU Xiaohan are co-first authors and contributed equally to this work -
Supported by:National Natural Science Foundation of China: to Explore the Molecular Mechanism of Treating Ankylosing Spondylitis by Invigorating Kidney and Activating Blood from the Regulation of T helper 17 Cells Differentiation and Migration by Histone Histone H3 Lysine 27 Trimethylation(81873292);Science and Technology Innovation Project of China Academy of Chinese Medical Sciences: Evaluation of Curative Effect and Molecular Mechanism of Shenqiangji Decoction in the Treatment of Ankylosing Spondylitis by Standard Control and Intervention in the Imaging Progress of Spinal Spondylitis(CI2021A01506);High Level Chinese Medical Hospital Promotion Project: Research and Development of Traditional Chinese Medicine Preparation for Treating Ankylosing Spondylitis with Danxian Bushen Qiangji Granules(HLCMHPP2023049)
Cite this article
GONG Yifan, XU Xiaohan, MA Jie, PANG Bo, LIU Wanlin, LIU Hongxiao. Multi-omics-based study on the biological characteristics of kidney renal deficiency and blood stasis in ankylosing spondylitis[J]. Journal of Traditional Chinese Medicine, 2026, 46(1): 183-194.
share this article
Table 1 Comparison of the general conditions of the study population
| Variable | Healthy volunteer group (n = 10) | SX group (n = 69) | SR group (n = 31) | P value |
|---|---|---|---|---|
| RNA-seq | ||||
| Male [n (%)] | 6 (60.0) | 45 (65.2) | 20 (64.5) | >0.05 |
| Female [n (%)] | 4 (40.0) | 24 (34.8) | 11 (35.5) | |
| Age (years) | 34±8 | 36±5 | 37±8 | >0.05 |
| Disease duration (years) | - | 11±9 | 10±9 | >0.05 |
| DIA-based proteomics | ||||
| Male [n (%)] | 31 (59.6) | 50 (63.3) | 21 (63.6) | >0.05 |
| Female [n (%)] | 21 (40.4) | 29 (36.7) | 12 (36.4) | |
| Age (years) | 33±6 | 35±9 | 36±8 | >0.05 |
| Disease duration (years) | - | 10±9 | 12±9 | >0.05 |
Table 1 Comparison of the general conditions of the study population
| Variable | Healthy volunteer group (n = 10) | SX group (n = 69) | SR group (n = 31) | P value |
|---|---|---|---|---|
| RNA-seq | ||||
| Male [n (%)] | 6 (60.0) | 45 (65.2) | 20 (64.5) | >0.05 |
| Female [n (%)] | 4 (40.0) | 24 (34.8) | 11 (35.5) | |
| Age (years) | 34±8 | 36±5 | 37±8 | >0.05 |
| Disease duration (years) | - | 11±9 | 10±9 | >0.05 |
| DIA-based proteomics | ||||
| Male [n (%)] | 31 (59.6) | 50 (63.3) | 21 (63.6) | >0.05 |
| Female [n (%)] | 21 (40.4) | 29 (36.7) | 12 (36.4) | |
| Age (years) | 33±6 | 35±9 | 36±8 | >0.05 |
| Disease duration (years) | - | 10±9 | 12±9 | >0.05 |
Figure 1 Differential gene analysis between AS and healthy controls A: volcano plot of differentially expressed genes in AS and N groups; B: GO enrichment analysis of all differences; C: KEGG enrichment analysis of all DEG. AS: ankylosing spondylitis; N: normal; GO: gene ontology; KEGG: Kyoto Encyclopedia of genes and Genomes.
Figure 1 Differential gene analysis between AS and healthy controls A: volcano plot of differentially expressed genes in AS and N groups; B: GO enrichment analysis of all differences; C: KEGG enrichment analysis of all DEG. AS: ankylosing spondylitis; N: normal; GO: gene ontology; KEGG: Kyoto Encyclopedia of genes and Genomes.
Figure 2 Differential protein analysis between SX and SR syndromes A: PCoA plot of protein profiles of SX and SR groups; B: volcano plot of differential proteins of SX and SR groups; C: sequencing plot of differential proteins of SX and SR groups. SX group: kidney deficiency and blood stasis syndrome; SR group: damp-heat stasis syndrome. PCoA: principal coordinates analysis; SX: kidney deficiency and blood stasis syndrome; SR: damp-heat stasis syndrome.
Figure 2 Differential protein analysis between SX and SR syndromes A: PCoA plot of protein profiles of SX and SR groups; B: volcano plot of differential proteins of SX and SR groups; C: sequencing plot of differential proteins of SX and SR groups. SX group: kidney deficiency and blood stasis syndrome; SR group: damp-heat stasis syndrome. PCoA: principal coordinates analysis; SX: kidney deficiency and blood stasis syndrome; SR: damp-heat stasis syndrome.
Figure 3 Identification and enrichment analysis of associated genes A: Wayne's plot of DEG association with DEP; B: GO-enriched bar graph of 36 associated genes; C: KEGG enrichment analysis of 36 upregulated genes; D: KEGG pathway enrichment analysis of 9 down-regulated associated molecules. DEG: Differentially Expressed Gene; GO: Gene ontology; KEGG: Kyoto Encyclopedia of genes and Genomes.
Figure 3 Identification and enrichment analysis of associated genes A: Wayne's plot of DEG association with DEP; B: GO-enriched bar graph of 36 associated genes; C: KEGG enrichment analysis of 36 upregulated genes; D: KEGG pathway enrichment analysis of 9 down-regulated associated molecules. DEG: Differentially Expressed Gene; GO: Gene ontology; KEGG: Kyoto Encyclopedia of genes and Genomes.
Figure 4 Validation of potential biomarkers for SX syndrome between the SX and SR groups A: relative mRNA level of ICAM1; B: relative mRNA level of SOCS3; C: relative mRNA level of IGFBP1; D: Relative mRNA level of CXCL8; E: relative mRNA level of MST1; F: relative protein level of ICAM1. The SX group (n = 69) represents patients with kidney deficiency and blood stasis syndrome. The SR group (n = 31) represents patients with damp-heat stasis syndrome; ICAM1: intercellular adhesion molecule 1; SOCS3: suppressor of cytokine signaling 3; IGFBP1: insulin-like growth factor binding protein 1; CXCL8: C-X-C motif chemokine ligand 8; MST1: macrophage stimulating 1; SX: kidney deficiency and blood stasis syndrome; SR: damp-heat stasis syndrome. Statistical significance between the two groups was determined by an unpaired Student’s t-test. Data are presented as mean ± standard deviation. aP < 0.001, compared to the SR group.
Figure 4 Validation of potential biomarkers for SX syndrome between the SX and SR groups A: relative mRNA level of ICAM1; B: relative mRNA level of SOCS3; C: relative mRNA level of IGFBP1; D: Relative mRNA level of CXCL8; E: relative mRNA level of MST1; F: relative protein level of ICAM1. The SX group (n = 69) represents patients with kidney deficiency and blood stasis syndrome. The SR group (n = 31) represents patients with damp-heat stasis syndrome; ICAM1: intercellular adhesion molecule 1; SOCS3: suppressor of cytokine signaling 3; IGFBP1: insulin-like growth factor binding protein 1; CXCL8: C-X-C motif chemokine ligand 8; MST1: macrophage stimulating 1; SX: kidney deficiency and blood stasis syndrome; SR: damp-heat stasis syndrome. Statistical significance between the two groups was determined by an unpaired Student’s t-test. Data are presented as mean ± standard deviation. aP < 0.001, compared to the SR group.
| 1. |
Sieper J, Poddubnyy D. Axial spondyloarthritis. Lancet 2017; 390: 73-84.
DOI PMID |
| 2. |
Zhu W, He X, Cheng K, et al. Ankylosing spondylitis: etiology, pathogenesis, and treatments. Bone Res 2019; 7: 22.
DOI PMID |
| 3. | Lai SW, Kuo YH, Liao KF. Incidence of inflammatory bowel disease in patients with ankylosing spondylitis. Ann Rheum Dis 2021; 80. |
| 4. |
Dean LE, Jones GT, Macdonald AG, et al. Global prevalence of ankylosing spondylitis. Rheumatology (Oxford) 2014; 53: 650-7.
DOI PMID |
| 5. |
Schett G, Lories RJ, D'agostino MA, et al. Enthesitis: from pathophysiology to treatment. Nat Rev Rheumatol 2017; 13: 731-41.
DOI PMID |
| 6. |
Kang H, Zhao Y, Li C, et al. Integrating clinical indexes into four-diagnostic information contributes to the Traditional Chinese Medicine (TCM) syndrome diagnosis of chronic hepatitis B. Sci Rep 2015; 5: 9395.
DOI PMID |
| 7. | Jian GH, Wu BY, Qi XY, et al. Review of the research on systems biology of Traditional Chinese Medicine for knee osteoarthritis. Shi Jie Ke Xue Ji Shu-Zhong Yi Yao Xian Dai Hua 2022; 24: 3339-45. |
| 8. | Hu ZF, Xiao C, He Y, et al. Systems biology will promote the development of Traditional Chinese Medicine. Shanghai Zhong Yi Yao Za Zhi 2007; 41: 1-4. |
| 9. | Cheung F. TCM: made in China. Nature 2011; 480: 82-3. |
| 10. |
Liu CM, Mao LG, Ping ZP, et al. Serum protein KNG1, APOC3, and PON1 as potential biomarkers for Yin-deficiency-heat syndrome. Evid Based Complement Alternat Med 2016; 2016: 5176731.
DOI URL |
| 11. |
Sun LC, Hu SS, Yu L, et al. Serum haptoglobin as a novel molecular biomarker predicting colorectal cancer hepatic metastasis. Int J Cancer 2016; 138: 2724-31.
DOI PMID |
| 12. |
Wiese S, Reidegeld KA, Meyer HE, Warscheid B. Protein labeling by iTRAQ: a new tool for quantitative mass spectrometry in proteome research. Proteomics 2007; 7: 340-50.
DOI PMID |
| 13. | Sun ZL, Wang MM, Xu X, et al. Proteomic study of serum proteins in rheumatic diseases with damp-heat syndrome based on iTRAQ labeling and bioinformatics technology. Nanjing Zhong Yi Yao Da Xue Xue Bao 2016; 32: 316-21. |
| 14. | Sun ZL, Xu X, Wang L, et al. Differential proteomics study of serum in ankylosing spondylitis with damp-heat blockage syndrome. Nanjing Zhong Yi Yao Da Xue Xue Bao 2015; 31: 412-5. |
| 15. | Wang MM, Wang L, Wang FQ, et al. Proteomics study of serum in ankylosing spondylitis with cold-damp blockage syndrome. Zhong Guo Zhong Yi Gu Shang Ke Za Zhi 2015; 23: 9-11. |
| 16. | Van Der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984; 27: 361-8. |
| 17. |
Zeidler H, Amor B. The Assessment in Spondyloarthritis International Society (ASAS) classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general: the spondyloarthritis concept in progress. Ann Rheum Dis 2011; 70: 1-3.
DOI PMID |
| 18. | Zheng XY. Guidance principles of clinical research on new drugs of Traditional Chinese Medicine. Beijing China Medical Science Press, 2002: 85-9. |
| 19. |
Kim D, Langmead B, Salzberg SL. HISAT: a fast spliced aligner with low memory requirements. Nat Methods 2015; 12: 357-60.
DOI PMID |
| 20. | Li B, Dewey CN. RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics 2011; 12: 323. |
| 21. |
Wang L, Feng Z, Wang X, et al. DEGseq: an R package for identifying differentially expressed genes from RNA-seq data. Bioinformatics 2010; 26: 136-8.
DOI PMID |
| 22. |
Zhang X, Ding W. Association of genetic variants in pentraxin 3 gene with ankylosing spondylitis. Med Sci Monit 2016; 22: 2911-6.
DOI URL |
| 23. |
Camozzi M, Rusnati M, Bugatti A, et al. Identification of an antiangiogenic FGF2-binding site in the N terminus of the soluble pattern recognition receptor PTX3. J Biol Chem 2006; 281: 22605-13.
DOI PMID |
| 24. | Xu HX, Yu HY, Liu LX, et al. Integrative single-Cell RNA-Seq and ATAC-Seq analysis of peripheral mononuclear cells in patients with ankylosing spondylitis. Front Immunol 2021; 12: 789. |
| 25. |
Wang L, Yang X, Cai GQ, et al. Association study of copy number variants in FCGR3A and FCGR3B gene with risk of ankylosing spondylitis in a Chinese population. Rheumatol Int 2016; 36: 437-42.
DOI PMID |
| 26. |
Uddin M, Maksymowych WP, Inman R, et al. UGT2B 17 copy number gain in a large ankylosing spondylitis multiplex family. BMC Genet 2013; 14: 67.
DOI |
| 27. |
Cortes A, Hadler J, Pointon JP, et al. Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat Genet 2013; 45: 730-8.
DOI PMID |
| 28. |
Lari A, Pourbadie HG, Sharifi-Zarchi A, et al. Dysregulation of ribosome-related genes in ankylosing spondylitis: a systems biology approach and experimental method. BMC Musculoskelet Disord 2021; 22: 789.
DOI |
| 29. |
Yu CJ, Zhan XL, Liang T, et al. Mechanism of hip arthropathy in ankylosing spondylitis: abnormal myeloperoxidase and phagosome. Front Immunol 2021; 12: 572592.
DOI URL |
| 30. |
Vishwakarma SK, Lakkireddy C, Sravani G, et al. Association of CD14 and macrophage migration inhibitory factor gene polymorphisms with inflammatory microRNAs expression levels in ankylosing spondylitis and polyarthralgia. Int J Immunogenet 2018; 45: 190-200.
DOI PMID |
| 31. | Zeng HS, Chen XY, Luo XP. The Association with the -159C/T polymorphism in the promoter region of the CD14 gene and juvenile idiopathic arthritis in a Chinese Han population. J Rheumatol 2009; 36: 1635-7. |
| 32. | Liu C, Ma J, Zhang X, et al. The role of IL-23/IL-17 axis in the pathogenesis of ankylosing spondylitis. Clin Rheumatol 2015; 34: 291-300. |
| 33. |
Reveille JD, Sims AM, Danoy P, et al. Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nat Genet 2010; 42: 123-7.
DOI PMID |
| 34. |
Brown MA, Wordsworth BP, Reveille JD. Genetics of ankylosing spondylitis. Clin Exp Rheumatol 2002; 20: S43-9.
PMID |
| 35. |
Stolwijk C, van Onna M, Boonen A, et al. Global prevalence of spondyloarthritis: a systematic review and meta-regression analysis. Arthritis Care Res (Hoboken) 2016; 68: 1320-31.
DOI PMID |
| 36. |
Brown MA, Kenna T, Wordsworth BP. Genetics of ankylosing spondylitis—insights into pathogenesis. Nat Rev Rheumatol 2016; 12: 81-91.
DOI |
| 37. |
Haroon N, Inman RD, Learch TJ, et al. The impact of tumor necrosis factor α inhibitors on radiographic progression in ankylosing spondylitis. Arthritis Rheum 2013; 65: 2645-54.
DOI URL |
| 38. | McKenna TJ, Molony J. Treatment of ankylosing spondylitis. Drugs 2013; 73: 481-500. |
| [1] | LI Junwei, LIU Xinyue, MOU Xuan, XIE Hongliang, GAO Yating, ZHANG Aolin, HE Tao, YEUNG Tszching, TANG Chao, WU Xiaoke, FAN Xiaohui, WANG Chichiu, LI Lu. Therapeutic effect and anti-inflammatory mechanism of modified Shoutai pills (改良寿胎丸) against lipopolysaccharide-induced miscarriage in mice [J]. Journal of Traditional Chinese Medicine, 2026, 46(1): 22-33. |
| [2] | FENG Chuwen, LI Chaoran, Yang Yan, QU Yuanyuan, SUN Zhongren, SUN Weibo, LIU Tingting, LI Shulin, Yang Tiansong. Identifying potential biomarkers in the hippocampus of chronic fatigue syndrome rats treated with moxibustion at Zusanli (ST36): a proteomics study [J]. Journal of Traditional Chinese Medicine, 2025, 45(3): 571-585. |
| [3] | LI Yajing, WANG Baoying, SHAO Wenxue, LU Shuaifei, SU Pan, BAI Ming, XU Erping, LI Yucheng. Quantitative proteomic analysis of the brain reveals the potential antidepressant mechanism of Jiawei Danzhi Xiaoyao San (加味丹栀逍遥散) in a chronic unpredictable mild stress mouse model of depression [J]. Journal of Traditional Chinese Medicine, 2025, 45(1): 22-31. |
| [4] | WANG Zhibo, LI Ying, WANG Daoping, MA Bo, MIAO Lan, REN Junguo, LIU Jinghua, LIU Jianxun. Proteomics analysis of coronary atherosclerotic heart disease with different Traditional Chinese Medicine syndrome types before and after percutaneous coronary intervention [J]. Journal of Traditional Chinese Medicine, 2024, 44(3): 554-563. |
| [5] | HENG Xianpei, WANG Zhita, LI Liang, YANG Liuqing, HUANG Suping, JIN Lang, HE Weidong. Mechanisms of Dangua Fang (丹瓜方) in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics [J]. Journal of Traditional Chinese Medicine, 2024, 44(2): 334-344. |
| [6] | WEI Lexin, LI Weiyi, TIAN Ting, ZHANG Ning, YANG Shijing, YANG Dongqing, LI Guochun, YE Fang. Identification of novel biomarkers and therapeutic target candidates for stasis-heat symptom pattern of acute intracerebral hemorrhage by quantitative plasma proteomics [J]. Journal of Traditional Chinese Medicine, 2022, 42(4): 622-632. |
| [7] | CHEN Xiaole, WANG Peng, YANG Mengdie, ZHOU Wenjun, CHEN Jian, MENG Zhiqiang, SU Shibing. Therapeutic effect of Jianpi Liqi Fang(健脾理气方) combined with transcatheter arterial chemoembolization in patients with hepatocellular carcinoma and spleen deficiency syndrome [J]. Journal of Traditional Chinese Medicine, 2021, 41(1): 157-166. |
| [8] | Zhizhen Liu, Zongyang Yu, Xuenong OuYang, Jian Du, Xiaopeng Lan, Meng Zhao. Applied research on serum protein fingerprints for prediction of Qi deficiency syndrome and phlegm and blood stasis in patients with non-small cell lung cancer [J]. Journal of Traditional Chinese Medicine, 2012, 32(03): 350-354. |
| Viewed | ||||||
|
Full text |
|
|||||
|
Abstract |
|
|||||
