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Engineering >> 2019, Volume 5, Issue 5 doi: 10.1016/j.eng.2019.01.018

Traditional Chinese Medicine as a Treatment for Rheumatoid Arthritis: From Empirical Practice to Evidence-Based Therapy

a State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau  University of Science and Technology,
Macao, China
bState Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
cDepartment of Respiratory and Critical Care Medicine, Affiliated Taihe Hospital of Hubei University of Medicine, Hubei 442000, China
#These authors contributed equally.

Received: 2018-07-05 Revised: 2018-09-10 Accepted: 2019-01-05 Available online: 2019-08-22

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Abstract

Rheumatoid arthritis (RA) is a common autoimmune condition with an elusive etiology. Conventional and biological disease-modifying drugs sometimes fail or produce only partial responses. Traditional Chinese medicine (TCM) has long been used in China as a treatment for RA and is achieving everincreasing acceptance worldwide. TCM treatments are traditionally guided by the theory of treatment based on TCM syndrome differentiation; however, they remain a matter of empirical practice relying on TCM theories and doctors’ own experience, which places severe restrictions on worldwide TCM application. Nevertheless, TCM is a treasure trove for drug discovery, particularly as a treatment for complicated human conditions. The discoveries of artemisinin as a treatment for malaria and of TCM–arsenic trioxide (As2O3) combination therapy as a treatment for acute promyelocytic leukemia (APL) are excellent examples of the great value of TCM. Regarding RA treatments, many Chinese medicinal herbs and their formulas, extracts, ingredients, and even single compounds have been used in clinical applications. Several Chinese proprietary medicines (CPMs) derived from TCM formulas or herbal bioactive components, such as the controlled-release tablets of ZhengQingFengTongNing (ZQFTN), tripterygium glycoside tablets, and capsules of total glucosides of peony (TGP), have been included in the National Health Insurance Directory of China, and show comparable therapeutic efficacies to those of western chemical drugs with fewer side effects. As TCM research has advanced, particularly in the use of multidisciplinary technologies, the scientific foundations and characteristics of the use of TCM to treat RA have been revealed, and the quality of TCM treatments have been increasingly enhanced. However, TCM generally lacks sufficient clinical and laboratory data to be consistent with international standards for quality, safety, and efficacy in order to support its application worldwide. Therefore, intensive basic and clinical studies on TCM are required. In particular, investigations that use cutting-edge technologies in analytical chemistry, biology, and biomedical sciences, and the development of randomized clinical trials (RCTs) and personalized pragmatic randomized controlled trials (PPRCTs) are necessary. Researchers should also collaborate to advance TCM from empirical practice to evidence-based therapy, thus consistently promoting TCM development and globalization in a vital, beneficial, and contributable manner.

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References

[ 1 ] McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med 2011;365(23):2205–19. link1

[ 2 ] Firestein GS. Evolving concepts of rheumatoid arthritis. Nature 2003;423 (6937):356–61. link1

[ 3 ] Cross M, Smith E, Hoy D, Carmona L, Wolfe F, Vos T, et al. The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 2014;73(7):1316–22. link1

[ 4 ] Di WT, Vergara F, Bertiller E, Gallardo ML, Gandino I, Scolnik M, et al. Incidence and prevalence of rheumatoid arthritis in a health management organization in Argentina: a 15-year study. J Rheumatol 2016;43 (7):1306–11. link1

[ 5 ] Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet 2010;376 (9746):1094–108. link1

[ 6 ] Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, et al.; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum 2008;58(1):26–35. link1

[ 7 ] Symmons DP, Barrett EM, Bankhead CR, Scott DG, Silman AJ. The incidence of rheumatoid arthritis in the United Kingdom: results from the Norfolk Arthritis Register. Br J Rheumatol 1994;33(8):735–9. link1

[ 8 ] Collison J. Rheumatoid arthritis: new player in RA pathogenesis brought to light. Nat Rev Rheumatol 2017;13(4):195. link1

[ 9 ] Kochi Y, Suzuki A, Yamada R, Yamamoto K. Ethnogenetic heterogeneity of rheumatoid arthritis-implications for pathogenesis. Nat Rev Rheumatol 2010;6(5):290–5. link1

[10] Visser H, le Cessie S, Vos K, Breedveld FC, Hazes JM. How to diagnose rheumatoid arthritis early: a prediction model for persistent (erosive) arthritis. Arthritis Rheum 2002;46(2):357–65. link1

[11] Smolen JS, Landewé R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017;76(6):960–77. link1

[12] Chou MH, Wang JY, Lin CL, Chung WS. DMARD use is associated with a higher risk of dementia in patients with rheumatoid arthritis: a propensity scorematched case-control study. Toxicol Appl Pharmacol 2017;334:217–22. link1

[13] Albrecht K, Müller-Ladner U. Side effects and management of side effects of methotrexate in rheumatoid arthritis. Clin Exp Rheumatol 2010;28(5 Suppl 61):S95–101. link1

[14] Simmons DL. Targeting kinases: a new approach to treating inflammatory rheumatic diseases. Curr Opin Pharmacol 2013;13(3):426–34. link1

[15] Smolen JS, Landewé R, Breedveld FC, Buch M, Burmester G, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2014;73(3):492–509. link1

[16] Wang XR, Su Y, An Y, Zhou YS, Zhang XY, Duan TJ, et al. Survey of tumor necrosis factor inhibitors application in patients with rheumatoid arthritis in China. J Peking Univ Health Sci 2012;44(2):182–7. link1

[17] An Y, Liu T, He D, Wu L, Li J, Liu Y, et al. The usage of biological DMARDs and clinical remission of rheumatoid arthritis in China: a real-world large scale study. Clin Rheumatol 2017;36(1):35–43. link1

[18] Buch MH. Defining refractory rheumatoid arthritis. Ann Rheum Dis 2018;77 (7):966–9. link1

[19] Greenberg JD, Reed G, Kremer JM, Tindall E, Kavanaugh A, Zheng C, et al.; CORRONA Investigators. Association of methotrexate and tumour necrosis factor antagonists with risk of infectious outcomes including opportunistic infections in the CORRONA registry. Ann Rheum Dis 2010;69(2):380–6. link1

[20] Raaschou P, Simard JF, Holmqvist M, Askling J; ARTIS Study Group. Rheumatoid arthritis, anti-tumour necrosis factor therapy, and risk of malignant melanoma: nationwide population based prospective cohort study from Sweden. BMJ 2013;346:f1939. link1

[21] Manheimer E, Wieland S, Kimbrough E, Cheng K, Berman BM. Evidence from the Cochrane Collaboration for traditional Chinese medicine therapies. J Altern Complement Med 2009;15(9):1001–14. link1

[22] Tu Y. Artemisinin—a gift from traditional Chinese medicine to the world (Nobel lecture). Angew Chem Int Ed Engl 2016;55(35):10210–26. link1

[23] Liu J, Chen Z. Traditional Chinese medicine in the new century. Front Med 2011;5(2):111–4. link1

[24] Hu J, Liu YF, Wu CF, Xu F, Shen ZX, Zhu YM, et al. Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci USA 2009;106 (9):3342–7. link1

[25] Shen ZX, Shi ZZ, Fang J, Gu BW, Li JM, Zhu YM, et al. All-trans retinoic acid/ As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci USA 2004;101 (15):5328–35. link1

[26] Zhang P, Li J, Han Y, Yu XW, Qin L. Traditional Chinese medicine in the treatment of rheumatoid arthritis: a general review. Rheumatol Int 2010;30(6):713–8. link1

[27] Lv QW, Zhang W, Shi Q, Zheng WJ, Li X, Chen H, et al. Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of active rheumatoid arthritis (TRIFRA): a randomised, controlled clinical trial. Ann Rheum Dis 2015;74(6):1078–86. link1

[28] Zhou YZ, Zhao LD, Chen H, Zhang Y, Wang DF, Huang LF, et al. Comparison of the impact of Tripterygium wilfordii Hook F and methotrexate treatment on radiological progression in active rheumatoid arthritis: 2-year follow up of a randomized, non-blinded, controlled study. Arthritis Res Ther 2018;20(1):70. link1

[29] Zhang EQ. Bi syndrome (arthralgia syndrome). J Tradit Chin Med 2010;30 (2):145–52. link1

[30] He W, Zhang J, Gu SZ. Clinical observation on needle-sticking method for treatment of rheumatoid arthritis of wind-cold-damp retention type. Chin Acupunct Moxibustion 2006;26(5):331–4. Chinese. link1

[31] Aikman H. The association between arthritis and the weather. Int J Biometeorol 1997;40(4):192–9. link1

[32] Jiang M, Xiao C, Chen G, Lu C, Zha Q, Yan X, et al. Correlation between cold and hot pattern in traditional Chinese medicine and gene expression profiles in rheumatoid arthritis. Front Med 2011;5(2):219–28. link1

[33] Sun Z. A study of relation between rheumatoid arthritis (RA) and blood stasis—the effect of acupuncture promoting blood circulation to remove blood stasis. Acupunct Res 1995;20(2):71–5. Chinese. link1

[34] Lo LC, Chen CY, Chiang JY, Cheng TL, Lin HJ, Chang HH. Tongue diagnosis of traditional Chinese medicine for rheumatoid arthritis. Afr J Tradit Complement Altern Med 2013;10(5):360–9. link1

[35] Guo Q, Zheng K, Fan D, Zhao Y, Li L, Bian Y, et al. Wu-Tou decoction in rheumatoid arthritis: integrating network pharmacology and in vivo pharmacological evaluation. Front Pharmacol 2017;8:230. link1

[36] Guo Q, Mao X, Zhang Y, Meng S, Xi Y, Ding Y, et al. Guizhi–Shaoyao–Zhimu decoction attenuates rheumatoid arthritis partially by reversing inflammation-immune system imbalance. J Transl Med 2016;14(1):165. link1

[37] Wang T, Lin J, Di SN, Kuang HX. The clinical effective observation of Wuton decoction and its disassembled prescriptions on TNF-a and IL-6 of 60 patients with rheumatoid arthritis. Acta Chin Med Pharmacol 2016;44(1):85–7. Chinese. link1

[38] Liu XM. Clinical observation of the effects of Wutou decoction and leflunomide combination treatment on rheumatoid arthritis patients in cold-dampness syndrome. China Rural Health 2015(4):20–1. Chinese. link1

[39] Zheng W. Clinical curative effect observation of Wu Tou decoction combined with leflunomide in the treatment of rheumatoid arthritis. Chin Community Doct 2016;12(10):109–10. Chinese. link1

[40] Li SR, Xie X. Clinical observation of the effects of Wutou decoction and methotrexate combination treatment on rheumatoid arthritis. J Pract Tradit Chin Med 2016;8:794. Chinese. link1

[41] Daily JW, Zhang T, Cao S, Park S. Efficacy and safety of GuiZhi–ShaoYao– ZhiMu decoction for treating rheumatoid arthritis: a systematic review and meta-analysis of randomized clinical trials. J Altern Complement Med 2017;23(10):756–70. link1

[42] Zhao J, Zha Q, Jiang M, Cao H, Lu A. Expert consensus on the treatment of rheumatoid arthritis with Chinese patent medicines. J Altern Complement Med 2013;19(2):111–8. link1

[43] Li WY, Song GP, Zou YQ, He CB. Clinical observation of senile rheumatoid arthritis treated with traditional Chinese medicine Duhuo Jisheng Decoction combined with ieflunomide. Chin Tradit Pat Med 2012;6:1004–6. Chinese. link1

[44] Chen XP, Li MY, Li J, Li CB. Treating 50 cases of blockage of rheumatoid arthritis hot and humid with Danggui Niantong decoction. Clin J Chin Med 2010;2(23):78. Chinese. link1

[45] Jiang M, Lu C, Zhang C, Yang J, Tan Y, Lu A, et al. Syndrome differentiation in modern research of traditional Chinese medicine. J Ethnopharmacol 2012;140(3):634–42. link1

[46] Yan E, Song J, Liu C, Hong W. A research on syndrome element differentiation based on phenomenology and mathematical method. Chin Med 2017;12:19. link1

[47] Yi YD, Chang IM. An overview of traditional Chinese herbal formulae and a proposal of a new code system for expressing the formula titles. Evid Based Complement Alternat Med 2004;1(2):125–32. link1

[48] Wang L, Zhou GB, Liu P, Song JH, Liang Y, Yan XJ, et al. Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia. Proc Natl Acad Sci USA 2008;105(12):4826–31. link1

[49] Chan TY. Aconite poisoning. Clin Toxicol (Phila) 2009;47(4):279–85. link1

[50] Song S, Tang Q, Huo H, Li H, Xing X, Luo J. Simultaneous quantification and pharmacokinetics of alkaloids in herba ephedrae–radix aconiti lateralis extracts. J Anal Toxicol 2015;39(1):58–68. link1

[51] Shahzad M, Shabbir A, Wojcikowski K, Wohlmuth H, Gobe GC. The antioxidant effects of radix astragali (astragalus membranaceus and related species) in protecting tissues from injury and disease. Curr Drug Targets 2016;17(12):1331–40. link1

[52] Yue H, Pi ZF, Song FR, Liu ZQ, Liu SY. Analysis of aconite alkaloids in the combination of radix aconiti lateralis preparata with different herbs by ESIMS spectrometry. Acta Pharm Sin 2007;42(2):201–5. Chinese. link1

[53] Yang Y, Yin XJ, Guo HM, Wang RL, Song R, Tian Y, et al. Identification and comparative analysis of the major chemical constituents in the extracts of single fuzi herb and fuzi-gancao herb-pair by UFLC-IT-TOF/MS. Chin J Nat Med 2014;12(7):542–53. link1

[54] Xu T, Pi Z, Liu S, Song F, Liu Z. Chemical profiling combined with ‘‘Omics” technologies (CP-Omics): a strategy to understand the compatibility mechanisms and simplify herb formulas in traditional Chinese medicines. Phytochem Anal 2017;28(5):381–91. link1

[55] Wu J, Xie Y, Xiang Z, Wang C, Zhou H, Liu L. Simultaneous determination of multiple components in Guanjiekang in rat plasma via the UPLC-MS/MS method and its application in pharmacokinetic study. Molecules 2016;21 (12):E1732. link1

[56] Wang XN, Zhou V, Liu Q, Gao Y, Zhou XH. Evaluation of the accuracy of diagnostic scales for a syndrome in Chinese medicine in the absence of a gold standard. Chin Med 2016;11:35. link1

[57] Wang J, Guo Y, Li GL. Current status of standardization of traditional Chinese medicine in China. Evid Based Complement Alternat Med 2016;2016:9123103. link1

[58] Wang M, Chen G, Lu C, Xiao C, Li L, Niu X, et al. Rheumatoid arthritis with deficiency pattern in traditional Chinese medicine shows correlation with cold and hot patterns in gene expression profiles. Evid Based Complement Alternat Med 2013;2013:248650. link1

[59] Seca S, Franconi G. Understanding Chinese medicine patterns of rheumatoid arthritis and related biomarkers. Medicines (Basel) 2018;5(1):E17. link1

[60] Jie HY, Wu QF, Ding ZX. Clinical study of Biqi Capsule combined with methotrexate for treatment of rheumatoid arthritis. Chin J Integr Tradit West Med 2012;32(2):195–8. Chinese. link1

[61] Lin CS, Yang XY, Dai L. Multi-center clinical study on therapeutic effect of kunxian capsule on rheumatoid arthritis. Chin J Integr Tradit West Med 2011;31(6):769–74. Chinese. link1

[62] He XC, Hu WM, Yang YH, Xu GM. Clinical observation Tong-Bi-Granules (TBG) combined methotrexate (MTX) therapy in elderly RA. China Health Care Nutr 2014;6:3781. Chinese. link1

[63] Du TX, Ren HY, Li GL. A clinical observation of Hanshibi pill for rheumatism of type of simultaneous occurrence of cold dampness syndromes. J Tradit Chin Orthop Traumatol 2002;14(8):5–7. Chinese. link1

[64] Man Y, Wang WZ. The effectiveness of Hanshibi pill in 89 rheumatoid arthritis patients. World Health Digest 2010;7(7):266–7. Chinese. link1

[65] Liang Q, Tang T, Zhang H. Clinical investigation of effects of bizhongxiao decoction (BZX) on rheumatoid arthritis on active phase. Bull Hunan Med Univ 2000;25(5):449–52. Chinese. link1

[66] He D, Shen J, Zhang Z, Lao Z. ‘‘Shi Re Bi Granule” for rheumatoid arthritis in 46 cases. Shanghai J Tradit Chin Med 2002;36(12):14–5. Chinese. link1

[67] Pang X, Meng Y. Effect of Rebi Kang Capsule for damp-heat rheumatoid arthritis: an observation of 86 cases. J Guangzhou Univ Tradit Chin Med 2003;20(2):106–8. Chinese. link1

[68] Li XF, Zhong ST, Zheng SM. Clinical research on rheumatoid arthritis treated with kidney-benefiting and arthritis-eliminating pill combined with leflunomide tablets. Henan Tradit Chin Med 2016;11:2007–9. Chinese. link1

[69] Zhou T. Study of Yishen Juanbi pills combined with methotrexate on elderly onset rheumatoid arthritis. Chin J Clin Ration Drug Use 2009;2(8):13–5. Chinese. link1

[70] Fu YF, Lou S, Chen JR, Zhang SL. Clinical study on wangbi capsules combined with methotrexate in the treatment of rheumatoid arthritis. China Pharm 2019;28(5):55–7. Chinese. link1

[71] Qiu D, Kao PN. Immunosuppressive and anti-inflammatory mechanisms of triptolide, the principal active diterpenoid from the Chinese medicinal herb Tripterygium wilfordii Hook. f. Drugs R D 2003;4(1):1–18. link1

[72] Liu L, Resch K, Kaever V. Inhibition of lymphocyte proliferation by the antiarthritic drug sinomenine. Int J Immunopharmacol 1994;16(8):685–91. link1

[73] Zhang MH, Feng L, Zhu MM, Gu JF, Wu C, Jia XB. Antioxidative and antiinflammatory activities of paeoniflorin and oxypaeoniflora on AGEs-induced mesangial cell damage. Planta Med 2013;79(14):1319–23. link1

[74] Kuang M, Cen Y, Qin R, Shang S, Zhai Z, Liu C, et al. Artesunate attenuates proinflammatory cytokine release from macrophages by inhibiting TLR4- mediated autophagic activation via the TRAF6-Beclin1-PI3KC3 pathway. Cell Physiol Biochem 2018;47(2):475–88. link1

[75] Wang HZ, Wang HH, Huang SS, Zhao H, Cao YG, Wang GZ, et al. Inhibitory effect of baicalin on collagen-induced arthritis in rats through the nuclear factor-jB pathway. J Pharmacol Exp Ther 2014;350(2):435–43. link1

[76] Su X, Huang Q, Chen J, Wang M, Pan H, Wang R, et al. Calycosin suppresses expression of pro-inflammatory cytokines via the activation of p62/Nrf2- linked heme oxygenase 1 in rheumatoid arthritis synovial fibroblasts. Pharmacol Res 2016;113(Pt A):695–704. link1

[77] Su X, Li T, Liu Z, Huang Q, Liao K, Ren R, et al. Licochalcone A activates Keap1- Nrf2 signaling to suppress arthritis via phosphorylation of p62 at serine 349. Free Radic Biol Med 2018;115:471–83. link1

[78] Li T, Wong VK, Jiang ZH, Jiang SP, Liu Y, Wang TY, et al. Mutation of cysteine 46 in IKK-beta increases inflammatory responses. Oncotarget 2015;6 (31):31805–19. link1

[79] Sakai E, Aoki Y, Yoshimatsu M, Nishishita K, Iwatake M, Fukuma Y, et al. Sanguiin H-6, a constituent of Rubus parvifolius L., inhibits receptor activator of nuclear factor-jB ligand-induced osteoclastogenesis and bone resorption in vitro and prevents tumor necrosis factor-a-induced osteoclast formation in vivo. Phytomedicine 2016;23(8):828–37. link1

[80] Lee G, Chung HS, Lee K, Lee H, Kim M, Bae H. Curcumin attenuates the scurfyinduced immune disorder, a model of IPEX syndrome, with inhibiting Th1/ Th2/Th17 responses in mice. Phytomedicine 2017;33:1–6. link1

[81] Wang QT, Zhang LL, Wu HX, Wei W. The expression change of b-arrestins in fibroblast-like synoviocytes from rats with collagen-induced arthritis and the effect of total glucosides of paeony. J Ethnopharmacol 2011;133(2):511–6. link1

[82] Hong R, Sur B, Yeom M, Lee B, Kim KS, Rodriguez JP, et al. Anti-inflammatory and anti-arthritic effects of the ethanolic extract of Aralia continentalis Kitag. in IL-1b-stimulated human fibroblast-like synoviocytes and rodent models of polyarthritis and nociception. Phytomedicine 2018;38:45–56. link1

[83] Zhou YY, Xia X, Peng WK, Wang QH, Peng JH, Li YL, et al. The effectiveness and safety of Tripterygium wilfordii Hook. F. extracts in rheumatoid arthritis: a systematic review and meta-analysis. Front Pharmacol 2018;9:356. link1

[84] Chen XM, Huang RY, Huang QC, Chu YL, Yan JY. Systemic review and metaanalysis of the clinical efficacy and adverse effects of Zhengqing Fengtongning combined with methotrexate in rheumatoid arthritis. Evid Based Complement Alternat Med 2015;2015:910376. link1

[85] Luo J, Jin DE, Yang GY, Zhang YZ, Wang JM, Kong WP, et al. Total glucosides of paeony for rheumatoid arthritis: a systematic review of randomized controlled trials. Complement Ther Med 2017;34:46–56. link1

[86] Lv QW, Chen T, Zhang W, Shi Q, Zheng WJ, Lipsky PE, et al. TwHF versus methotrexate in the treatment of rheumatoid arthritis: response to Landewe’s comment on the TRIFRA study. Ann Rheum Dis 2014;73(10):e63. link1

[87] Zhao XX, Peng C, Zhang H, Qin LP. Sinomenium acutum: a review of chemistry, pharmacology, pharmacokinetics, and clinical use. Pharm Biol 2012;50(8):1053–61. link1

[88] Zhou H, Liu JX, Luo JF, Cheng CS, Leung EL, Li Y, et al. Suppressing mPGES-1 expression by sinomenine ameliorates inflammation and arthritis. Biochem Pharmacol 2017;142:133–44. link1

[89] Hadjipavlou-Litina D. Quantitative structure–activity relationship (QSAR) studies on non steroidal anti-inflammatory drugs (NSAIDs). Curr Med Chem 2000;7(4):375–88. link1

[90] Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol 2011;31(5):986–1000. link1

[91] Borer JS, Simon LS. Cardiovascular and gastrointestinal effects of COX-2 inhibitors and NSAIDs: achieving a balance. Arthritis Res Ther 2005;7(Suppl 4):S14–22. link1

[92] Zhou H, Wong YF, Wang J, Cai X, Liu L. Sinomenine ameliorates arthritis via MMPs, TIMPs, and cytokines in rats. Biochem Biophys Res Commun 2008;376 (2):352–7. link1

[93] Gandhi GR, NetaMT, Sathiyabama RG, Quintans JS, de Oliveira E Silva AM, Araújo AA, et al. Flavonoids as Th1/Th2 cytokines immunomodulators: a systematic review of studies on animal models. Phytomedicine 2018;44:74–84. link1

[94] Yi YS. Regulatory roles of flavonoids on inflammasome activation during inflammatory responses. Mol Nutr Food Res 2018;62(13):e1800147. link1

[95] Wang TY, Zhou H, Wong YF, Wu PK, Wl Hsiao, Leung EL, et al. The predicted proteomic network associated with the antiarthritic action of Qingfu Guanjieshu in collagen-II-induced arthritis in rats. Evid Based Complement Alternat Med 2013;2013:582493. link1

[96] Hu Y, Hu Z, Wang S, Dong X, Xiao C, Jiang M, et al. Protective effects of HuangLian-Jie-Du-Tang and its component group on collagen-induced arthritis in rats. J Ethnopharmacol 2013;150(3):1137–44. link1

[97] Fan XX, Leung EL, Xie Y, Liu ZQ, Zheng YF, Yao XJ, et al. Suppression of lipogenesis via reactive oxygen species-AMPK signaling for treating malignant and proliferative diseases. Antioxid Redox Signal 2018;28(5):339–57. link1

[98] Fan XX, Pan HD, Li Y, Guo RJ, Leung EL, Liu L. Novel therapeutic strategy for cancer and autoimmune conditions: modulating cell metabolism and redox capacity. Pharmacol Ther 2018;191:148–61. link1

[99] Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR, Macia L. The role of short-chain fatty acids in health and disease. Adv Immunol 2014;121: 91–119. link1

[100] Zhao L, Wu H, Zhao A, Lu H, Sun W, Ma C, et al. The in vivo and in vitro study of polysaccharides from a two-herb formula on ulcerative colitis and potential mechanism of action. J Ethnopharmacol 2014;153(1):151–9. link1

[101] Huang L, Lv Q, Xie D, Shi T, Wen C. Deciphering the potential pharmaceutical mechanism of Chinese traditional medicine (Gui-Zhi-Shao-Yao-Zhi-Mu) on rheumatoid arthritis. Sci Rep 2016;6(1):22602. link1

[102] Leung ELH, Wong VKW, Jiang ZH, Li T, Liu L. Integrated network-based medicine: the role of traditional Chinese medicine in developing a new generation of medicine. Science 2014;346:S16–8. link1

[103] Heidari B. Rheumatoid arthritis: early diagnosis and treatment outcomes. Caspian J Intern Med 2011;2(1):161–70. link1

[104] Raza K, Saber TP, Kvien TK, Tak PP, Gerlag DM. Timing the therapeutic window of opportunity in early rheumatoid arthritis: proposal for definitions of disease duration in clinical trials. Ann Rheum Dis 2012;71(12):1921–3. link1

[105] Jiang F, Jiang Y, Zhi H, Dong Y, Li H, Ma S, et al. Artificial intelligence in healthcare: past, present and future. Stroke Vasc Neurol 2017;2(4):230–43. link1

[106] AI diagnostics need attention. Nature 2018;555(7696):285–286

[107] Wang JR, Gao WN, Grimm R, Jiang S, Liang Y, Ye H, et al. A method to identify trace sulfated IgG N-glycans as biomarkers for rheumatoid arthritis. Nat Commun 2017;8(1):631. link1

[108] Ercan A, Cui J, Chatterton DE, Deane KD, Hazen MM, Brintnell W, et al. Aberrant IgG galactosylation precedes disease onset, correlates with disease activity, and is prevalent in autoantibodies in rheumatoid arthritis. Arthritis Rheum 2010;62(8):2239–48. link1

[109] Wijbrandts CA, Tak PP. Prediction of response to targeted treatment in rheumatoid arthritis. Mayo Clin Proc 2017;92(7):1129–43. link1

[110] Buriani A, Garcia-Bermejo ML, Bosisio E, Xu Q, Li H, Dong X, et al. Omic techniques in systems biology approaches to traditional Chinese medicine research: present and future. J Ethnopharmacol 2012;140(3):535–44. link1

[111] Hung SSC, Khan S, Lo CY, Hewitt AW, Wong RCB. Drug discovery using induced pluripotent stem cell models of neurodegenerative and ocular diseases. Pharmacol Ther 2017;177:32–43. link1

[112] Kurzrock R, Stewart DJ. Click chemistry, 3D-printing, and omics: the future of drug development. Oncotarget 2016;7(3):2155–8. link1

[113] Meng XY, Zhang HX, Mezei M, Cui M. Molecular docking: a powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des 2011;7(2):146–57. link1

[114] Liu L, Leung EL, Tian X. Perspective: the clinical trial barriers. Nature 2011;480(7378):S100. link1

[115] Gao H, Wang Z, Li Y, Qian Z. Overview of the quality standard research of traditional Chinese medicine. Front Med 2011;5(2):195–202. link1

[116] Liu CX, Liu L, Guo DA. Quality marker of TCMs: concept and applications. Phytomedicine 2018;44:85–6. link1

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