Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Computer - Aided Drug Design
  4. Fast Track Articles
  5. Fast Track Article
image of Network Pharmacology and In Vivo Experimental Verification of the Mechanism of the Qing'e Pill for Treating Intervertebral Disc Degeneration
file format pdf download PDF

Abstract

Objective

The Qing’e Pill (QEP) is widely used to alleviate low back pain and sciatica caused by Intervertebral Disc Degeneration (IDD). However, its active components, key targets, and molecular mechanisms are not fully understood. The aim of this study is to elucidate the molecular mechanisms through which the QEP improves IDD using database mining techniques.

Methods

Active components and candidate targets of the QEP were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine. IDD-related targets were obtained from the GeneCards database, and liver- and kidney-specific genes were retrieved from the BioGPS database. The intersection of these candidate targets was analyzed to identify potential targets for the QEP in IDD. A protein-protein interaction network analysis was performed using STRING and Cytoscape 3.7.2 software. Core targets were further analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking was used to assess the binding affinity of active components to candidate targets, and animal experiments were conducted for validation.

Results

We identified 65 potentially active components of the QEP that corresponded to 1,093 candidate targets, 2,108 IDD-related targets, and 1,113 liver- and kidney-specific genes. Key components included quercetin, berberine, isorhamnetin, and emodin. The primary candidate targets were Wnt5A, CTNNB1, IL-1β, MAPK14, MMP9, and MMP3. The GO and KEGG analyses revealed the involvement of these targets in Wnt signaling, TNF signaling, Wnt receptor activation, Frizzled binding, and Wnt-protein interactions. Molecular docking showed strong binding between these components and their targets. Animal experiments demonstrated that the QEP treatment significantly reduced the expression of Wnt5A, CTNNB1, IL-1β, MAPK14, MMP9, and MMP3 at high, medium, and low doses compared with the model group.

Conclusion

The QEP alleviated IDD by modulating the Wnt/MAPK/MMP signaling pathways and reducing the release and activation of key factors.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cad/10.2174/0115734099356426241119051916
2024-12-02
2025-01-18

  • From This Site

    /content/journals/cad/10.2174/0115734099356426241119051916
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

/deliver/fulltext/cad/10.2174/0115734099356426241119051916/BMS-CCADD-2024-311.html?itemId=/content/journals/cad/10.2174/0115734099356426241119051916&mimeType=html&fmt=ahah

References

  1. Ito K. Creemers L. Mechanisms of intervertebral disk degeneration/injury and pain: A review. Global Spine J. 2013 3 3 145 151 10.1055/s‑0033‑1347300 24436865
    [Google Scholar]
  2. Hartvigsen J. Hancock M.J. Kongsted A. Louw Q. Ferreira M.L. Genevay S. Hoy D. Karppinen J. Pransky G. Sieper J. Smeets R.J. Underwood M. Buchbinder R. Hartvigsen J. Cherkin D. Foster N.E. Maher C.G. Underwood M. van Tulder M. Anema J.R. Chou R. Cohen S.P. Menezes Costa L. Croft P. Ferreira M. Ferreira P.H. Fritz J.M. Genevay S. Gross D.P. Hancock M.J. Hoy D. Karppinen J. Koes B.W. Kongsted A. Louw Q. Öberg B. Peul W.C. Pransky G. Schoene M. Sieper J. Smeets R.J. Turner J.A. Woolf A. What low back pain is and why we need to pay attention. Lancet 2018 391 10137 2356 2367 10.1016/S0140‑6736(18)30480‑X 29573870
    [Google Scholar]
  3. Chen N. Fong D.Y.T. Wong J.Y.H. Health and economic burden of low back pain and rheumatoid arthritis attributable to smoking in 192 countries and territories in 2019. Addiction 2023 119 4 add.16404 10.1111/add.16404 38105035
    [Google Scholar]
  4. Tingxi Z. Xiaojun S. Yijun S. Discussion on the treatment of low back pain with buguyao pain relief decoction combined with abdominal acupuncture. Chinese Clinic. Res. Tradit. Chinese Med. 2022 14 13 69 71
    [Google Scholar]
  5. Huibin C. Treatment of lumbar and knee coldness with Qing'e Pill. Benef. Read. Seek. Med. Advice. 2023 1 11
    [Google Scholar]
  6. Li X. Liu Z. Liao J. Chen Q. Lu X. Fan X. Network pharmacology approaches for research of Traditional Chinese Medicines. Chin. J. Nat. Med. 2023 21 5 323 332 10.1016/S1875‑5364(23)60429‑7 37245871
    [Google Scholar]
  7. Gao H. Chen Z. Halihaman B. Huang L. Wang Z. Ding X. Network pharmacology and in vitro experimental verification to explore the mechanism of chaiqin qingning capsule in the treatment of pain. Curr. Pharm. Des. 2024 30 4 278 294 10.2174/0113816128280351240112044430 38310568
    [Google Scholar]
  8. Xie C. Tang H. Liu G. Li C. Molecular mechanism of Epimedium in the treatment of vascular dementia based on network pharmacology and molecular docking. Front. Aging Neurosci. 2022 14 940166 10.3389/fnagi.2022.940166 36051307
    [Google Scholar]
  9. Ru J. Li P. Wang J. Zhou W. Li B. Huang C. Li P. Guo Z. Tao W. Yang Y. Xu X. Li Y. Wang Y. Yang L. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J. Cheminform. 2014 6 1 13 10.1186/1758‑2946‑6‑13 24735618
    [Google Scholar]
  10. Kong X. Liu C. Zhang Z. Cheng M. Mei Z. Li X. Liu P. Diao L. Ma Y. Jiang P. Kong X. Nie S. Guo Y. Wang Z. Zhang X. Wang Y. Tang L. Guo S. Liu Z. Li D. BATMAN-TCM 2.0: an enhanced integrative database for known and predicted interactions between traditional Chinese medicine ingredients and target proteins. Nucleic Acids Res. 2024 52 D1 D1110 D1120 10.1093/nar/gkad926 37904598
    [Google Scholar]
  11. Zhang Y. Liu T. Zhao Y. Zhao C. Zhao M. Deciphering the enigma between low bioavailability and high anti-hepatic fibrosis efficacy of Yinchen Wuling powder based on drug metabolism and network pharmacology. J. Ethnopharmacol. 2024 321 117538 10.1016/j.jep.2023.117538 38056536
    [Google Scholar]
  12. Bateman A. Martin M-J. Orchard S. Magrane M. Ahmad S. Alpi E. Bowler-Barnett E.H. Britto R. Bye-A-Jee H. Cukura A. Denny P. Dogan T. Ebenezer T.G. Fan J. Garmiri P. da Costa Gonzales L.J. Hatton-Ellis E. Hussein A. Ignatchenko A. Insana G. Ishtiaq R. Joshi V. Jyothi D. Kandasaamy S. Lock A. Luciani A. Lugaric M. Luo J. Lussi Y. MacDougall A. Madeira F. Mahmoudy M. Mishra A. Moulang K. Nightingale A. Pundir S. Qi G. Raj S. Raposo P. Rice D.L. Saidi R. Santos R. Speretta E. Stephenson J. Totoo P. Turner E. Tyagi N. Vasudev P. Warner K. Watkins X. Zaru R. Zellner H. Bridge A.J. Aimo L. Argoud-Puy G. Auchincloss A.H. Axelsen K.B. Bansal P. Baratin D. Batista Neto T.M. Blatter M-C. Bolleman J.T. Boutet E. Breuza L. Gil B.C. Casals-Casas C. Echioukh K.C. Coudert E. Cuche B. de Castro E. Estreicher A. Famiglietti M.L. Feuermann M. Gasteiger E. Gaudet P. Gehant S. Gerritsen V. Gos A. Gruaz N. Hulo C. Hyka-Nouspikel N. Jungo F. Kerhornou A. Le Mercier P. Lieberherr D. Masson P. Morgat A. Muthukrishnan V. Paesano S. Pedruzzi I. Pilbout S. Pourcel L. Poux S. Pozzato M. Pruess M. Redaschi N. Rivoire C. Sigrist C.J.A. Sonesson K. Sundaram S. Wu C.H. Arighi C.N. Arminski L. Chen C. Chen Y. Huang H. Laiho K. McGarvey P. Natale D.A. Ross K. Vinayaka C.R. Wang Q. Wang Y. Zhang J. UniProt: The universal protein knowledgebase in 2023. Nucleic Acids Res. 2023 51 D1 D523 D531 10.1093/nar/gkac1052 36408920
    [Google Scholar]
  13. Doncheva N.T. Morris J.H. Gorodkin J. Jensen L.J. Cytoscape StringApp: Network analysis and visualization of proteomics data. J. Proteome Res. 2019 18 2 623 632 10.1021/acs.jproteome.8b00702 30450911
    [Google Scholar]
  14. Stelzer G Rosen N Plaschkes I The genecards suite: From gene data mining to disease genome sequence analyses. Curr. Protoc. Bioinformatics 2016 54 1.30.1 1.30.33
    [Google Scholar]
  15. Wu C. Jin X. Tsueng G. Afrasiabi C. Su A.I. BioGPS: Building your own mash-up of gene annotations and expression profiles. Nucleic Acids Res. 2016 44 D1 D313 D316 10.1093/nar/gkv1104 26578587
    [Google Scholar]
  16. Szklarczyk D. Franceschini A. Kuhn M. Simonovic M. Roth A. Minguez P. Doerks T. Stark M. Muller J. Bork P. Jensen L.J. Mering C. The STRING database in 2011: Functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. 2011 39 Database D561 D568 10.1093/nar/gkq973 21045058
    [Google Scholar]
  17. Fan J. Zhou J. Qu Z. Peng H. Meng S. Peng Y. Liu T. Luo Q. Dai L. Network pharmacology and molecular docking elucidate the pharmacological mechanism of the OSTEOWONDER capsule for treating osteoporosis. Front. Genet. 2022 13 833027 10.3389/fgene.2022.833027 35295951
    [Google Scholar]
  18. Xiang Q. Zhao Y. Li W. Identification and validation of ferroptosis-related gene signature in intervertebral disc degeneration. Front. Endocrinol. 2023 14 1089796 10.3389/fendo.2023.1089796 36814575
    [Google Scholar]
  19. Ritchie M.E. Phipson B. Wu D. Hu Y. Law C.W. Shi W. Smyth G.K. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015 43 7 e47 10.1093/nar/gkv007 25605792
    [Google Scholar]
  20. Dennis G. Jr Sherman B.T. Hosack D.A. Yang J. Gao W. Lane H.C. Lempicki R.A. DAVID: Database for annotation, visualization, and integrated discovery. Genome Biol. 2003 4 5 P3 10.1186/gb‑2003‑4‑5‑p3 12734009
    [Google Scholar]
  21. Gao P. Chang K. Yuan S. Wang Y. Zeng K. Jiang Y. Tu P. Lu Y. Guo X. Exploring the mechanism of hepatotoxicity induced by Dictamnus dasycarpus based on network pharmacology, molecular docking and experimental pharmacology. Molecules 2023 28 13 5045 10.3390/molecules28135045 37446707
    [Google Scholar]
  22. Burley S.K. Berman H.M. Kleywegt G.J. Markley J.L. Nakamura H. Velankar S. Protein Data Bank (PDB): The single global macromolecular structure archive. Methods Mol. Biol. 2017 1607 627 641 10.1007/978‑1‑4939‑7000‑1_26 28573592
    [Google Scholar]
  23. Ji L. Song T. Ge C. Wu Q. Ma L. Chen X. Chen T. Chen Q. Chen Z. Chen W. Identification of bioactive compounds and potential mechanisms of scutellariae radix-coptidis rhizoma in the treatment of atherosclerosis by integrating network pharmacology and experimental validation. Biomed. Pharmacother. 2023 165 115210 10.1016/j.biopha.2023.115210 37499457
    [Google Scholar]
  24. Eberhardt J. Santos-Martins D. Tillack A.F. Forli S. AutoDock Vina 1.2.0: New docking methods, expanded force field, and python bindings. J. Chem. Inf. Model. 2021 61 8 3891 3898 10.1021/acs.jcim.1c00203 34278794
    [Google Scholar]
  25. Patel R. Prajapati J. Rao P. Rawal R.M. Saraf M. Goswami D. Repurposing the antibacterial drugs for inhibition of SARS-CoV2-PLpro using molecular docking, MD simulation and binding energy calculation. Mol. Divers. 2022 26 4 2189 2209 10.1007/s11030‑021‑10325‑0 34591234
    [Google Scholar]
  26. Fan C. Du J. Yu Z. Wang J. Yao L. Ji Z. He W. Deng Y. Geng D. Wu X. Mao H. Inhibition of MAGL attenuates intervertebral disc degeneration by delaying nucleus pulposus senescence through STING. Int. Immunopharmacol. 2024 131 111904 10.1016/j.intimp.2024.111904 38518595
    [Google Scholar]
  27. Fan H. Anqi D. Fan H. X-ray-guided establishment of rat intervertebral disc degeneration model. Chinese J. Tissue Engin. Res. 2022 26 35 5652 5657 [J].
    [Google Scholar]
  28. Niu B. Xie X. Xiong X. Jiang J. Network pharmacology-based analysis of the anti-hyperglycemic active ingredients of roselle and experimental validation. Comput. Biol. Med. 2022 141 104636 10.1016/j.compbiomed.2021.104636 34809966
    [Google Scholar]
  29. Yu X. Shi K. Wu B. Mechanism of Shenfu injection in treating ischemic stroke elucidated using network pharmacology and experimental validation. Curr. Comput. Aided Drug Des. 2024 Epub ahead of print. 10.2174/0115734099292513240404091734
    [Google Scholar]
  30. Kanehisa M. Furumichi M. Sato Y. Kawashima M. Ishiguro-Watanabe M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 2023 51 D1 D587 D592 10.1093/nar/gkac963 36300620
    [Google Scholar]
  31. Chen L. Zhang Y.H. Wang S. Zhang Y. Huang T. Cai Y.D. Prediction and analysis of essential genes using the enrichments of gene ontology and KEGG pathways. PLoS One 2017 12 9 e0184129 10.1371/journal.pone.0184129 28873455
    [Google Scholar]
  32. Zhang D. Qin H. Chen W. Xiang J. Jiang M. Zhang L. Zhou K. Hu Y. Utilizing network pharmacology, molecular docking, and animal models to explore the therapeutic potential of the WenYang FuYuan recipe for cerebral ischemia-reperfusion injury through AGE-RAGE and NF-κB/p38MAPK signaling pathway modulation. Exp. Gerontol. 2024 191 112448 10.1016/j.exger.2024.112448 38697555
    [Google Scholar]
  33. Hiyama A. Sakai D. Risbud M.V. Tanaka M. Arai F. Abe K. Mochida J. Enhancement of intervertebral disc cell senescence by WNT/β‐catenin signaling–induced matrix metalloproteinase expression. Arthritis Rheum. 2010 62 10 3036 3047 10.1002/art.27599 20533544
    [Google Scholar]
  34. Zhu D. Wang Z. Zhang G. Ma C. Qiu X. Wang Y. Liu M. Guo X. Chen H. Deng Q. Kang X. Periostin promotes nucleus pulposus cells apoptosis by activating the Wnt/β‐catenin signaling pathway. FASEB J. 2022 36 7 e22369 10.1096/fj.202200123R 35747912
    [Google Scholar]
  35. Alipour Noghabi S. Ghamari kargar P. Bagherzade G. Beyzaei H. Comparative study of antioxidant and antimicrobial activity of berberine-derived Schiff bases, nitro-berberine and amino-berberine. Heliyon 2023 9 12 e22783 10.1016/j.heliyon.2023.e22783 38058428
    [Google Scholar]
  36. Liu W. Du L. Cui Y. He C. He Z. WNT5A regulates the proliferation, apoptosis and stemness of human stem Leydig cells via the β-catenin signaling pathway. Cell. Mol. Life Sci. 2024 81 1 93 10.1007/s00018‑023‑05077‑z 38367191
    [Google Scholar]
  37. Smolders L.A. Meij B.P. Riemers F.M. Licht R. Wubbolts R. Heuvel D. Grinwis G.C.M. Vernooij H.C.M. Hazewinkel H.A.W. Penning L.C. Tryfonidou M.A. Canonical Wnt signaling in the notochordal cell is upregulated in early intervertebral disk degeneration. J. Orthop. Res. 2012 30 6 950 957 10.1002/jor.22000 22083942
    [Google Scholar]
  38. Johnson Z.I. Schoepflin Z.R. Choi H. Shapiro I.M. Risbud M.V. Disc in flames: Roles of TNF-α and IL-1β in intervertebral disc degeneration. Eur. Cell. Mater. 2015 30 104 117 10.22203/eCM.v030a08 26388614
    [Google Scholar]
  39. Zhang X. Zhang Z. Zou X. Wang Y. Qi J. Han S. Xin J. Zheng Z. Wei L. Zhang T. Zhang S. Unraveling the mechanisms of intervertebral disc degeneration: An exploration of the p38 MAPK signaling pathway. Front. Cell Dev. Biol. 2024 11 1324561 10.3389/fcell.2023.1324561 38313000
    [Google Scholar]
  40. Xu Y. Zhang Z. Zheng Y. Feng S. Dysregulated miR-133a mediates loss of type II collagen by directly targeting Matrix Metalloproteinase 9 (MMP9) in human intervertebral disc degeneration. Spine 2016 41 12 E717 E724 10.1097/BRS.0000000000001375 26656045
    [Google Scholar]
  41. Song Q. Zhang F. Wang K. Chen Z. Li Q. Liu Z. Shen H. MiR-874-3p plays a protective role in intervertebral disc degeneration by suppressing MMP2 and MMP3. Eur. J. Pharmacol. 2021 895 173891 10.1016/j.ejphar.2021.173891 33482178
    [Google Scholar]
  42. Wang X. He X. Zhang C.F. Guo C.R. Wang C.Z. Yuan C.S. Anti-arthritic effect of berberine on adjuvant-induced rheumatoid arthritis in rats. Biomed. Pharmacother. 2017 89 887 893 10.1016/j.biopha.2017.02.099 28282791
    [Google Scholar]
  43. Shi H. He J. Li X. Han J. Wu R. Wang D. Yang F. Sun E. Isorhamnetin, the active constituent of a Chinese herb Hippophae rhamnoides L, is a potent suppressor of dendritic-cell maturation and trafficking. Int. Immunopharmacol. 2018 55 216 222 10.1016/j.intimp.2017.12.014 29272818
    [Google Scholar]
  44. Seo K. Yang J.H. Kim S.C. Ku S.K. Ki S.H. Shin S.M. The antioxidant effects of isorhamnetin contribute to inhibit COX-2 expression in response to inflammation: A potential role of HO-1. Inflammation 2014 37 3 712 722 10.1007/s10753‑013‑9789‑6 24337631
    [Google Scholar]
  45. Albring K.F. Weidemüller J. Mittag S. Weiske J. Friedrich K. Geroni M.C. Lombardi P. Huber O. Berberine acts as a natural inhibitor of Wnt/β‐catenin signaling—Identification of more active 13‐arylalkyl derivatives. Biofactors 2013 39 6 652 662 10.1002/biof.1133 23982892
    [Google Scholar]
  46. Lee S.H. Kim B. Oh M.J. Yoon J. Kim H.Y. Lee K.J. Lee J.D. Choi K.Y. Persicaria hydropiper (L.) spach and its flavonoid components, isoquercitrin and isorhamnetin, activate the Wnt/β-catenin pathway and inhibit adipocyte differentiation of 3T3-L1 cells. Phytother. Res. 2011 25 11 1629 1635 10.1002/ptr.3469 21413092
    [Google Scholar]
  47. Li Z. Zhang K. Li X. Pan H. Li S. Chen F. Zhang J. Zheng Z. Wang J. Liu H. Wnt5a suppresses inflammation-driven intervertebral disc degeneration via a TNF-α/NF-κB–Wnt5a negative-feedback loop. Osteoarthritis Cartilage 2018 26 7 966 977 10.1016/j.joca.2018.04.002 29656141
    [Google Scholar]
  48. Ren X. Bao Y. Zhu Y. Liu S. Peng Z. Zhang Y. Zhou G. Isorhamnetin, hispidulin, and cirsimaritin identified in tamarix ramosissima barks from southern xinjiang and their antioxidant and antimicrobial activities. Molecules 2019 24 3 390 10.3390/molecules24030390 30678248
    [Google Scholar]
  49. An N. Zhang G. Li Y. Yuan C. Yang F. Zhang L. Gao Y. Xing Y. Promising antioxidative effect of berberine in cardiovascular diseases. Front. Pharmacol. 2022 13 865353 10.3389/fphar.2022.865353 35321323
    [Google Scholar]
  50. Tvrdá E. Kováč J. Ferenczyová K. Kaločayová B. Ďuračka M. Benko F. Almášiová V. Barteková M. Quercetin ameliorates testicular damage in zucker diabetic fatty rats through its antioxidant, anti-inflammatory and anti-apoptotic properties. Int. J. Mol. Sci. 2022 23 24 16056 10.3390/ijms232416056 36555696
    [Google Scholar]
  51. Tian S.L. Yang Y. Liu X.L. Xu Q.B. Emodin attenuates bleomycin-induced pulmonary fibrosis via anti-inflammatory and anti-oxidative activities in rats. Med. Sci. Monit. 2018 24 1 10 10.12659/MSM.905496 29290631
    [Google Scholar]
  52. Hao Y. Ren Z. Yu L. Zhu G. Zhang P. Zhu J. Cao S. p300 arrests intervertebral disc degeneration by regulating the FOXO3 /Sirt1/Wnt/β‐catenin axis. Aging Cell 2022 21 8 e13677 10.1111/acel.13677 35907249
    [Google Scholar]
  53. Zhang H.J. Liao H.Y. Bai D.Y. Wang Z.Q. Xie X.W. MAPK /ERK signaling pathway: A potential target for the treatment of intervertebral disc degeneration. Biomed. Pharmacother. 2021 143 112170 10.1016/j.biopha.2021.112170 34536759
    [Google Scholar]
  54. Liu S. Yang S.D. Huo X.W. 17β-Estradiol inhibits intervertebral disc degeneration by down-regulating MMP-3 and MMP-13 and up-regulating type II collagen in a rat model. Artif. Cells Nanomed. Biotechnol. 2018 46 S2 182 191
    [Google Scholar]
  55. Yurube T. Nishida K. Suzuki T. Kaneyama S. Zhang Z. Kakutani K. Maeno K. Takada T. Fujii M. Kurosaka M. Doita M. Matrix metalloproteinase (MMP)‐3 gene up‐regulation in a rat tail compression loading‐induced disc degeneration model. J. Orthop. Res. 2010 28 8 1026 1032 10.1002/jor.21116 20162718
    [Google Scholar]
  56. Le Maitre C.L. Freemont A.J. Hoyland J.A. The role of interleukin-1 in the pathogenesis of human Intervertebral disc degeneration. Arthritis Res. Ther. 2005 7 4 R732 R745 10.1186/ar1732 15987475
    [Google Scholar]
  57. Kusakabe T. Sawaji Y. Endo K. Suzuki H. Konishi T. Maekawa A. Murata K. Yamamoto K. DUSP-1 induced by PGE2 and PGE1 attenuates il-1β-activated MAPK signaling, leading to suppression of NGF expression in human intervertebral disc cells. Int. J. Mol. Sci. 2021 23 1 371 10.3390/ijms23010371 35008797
    [Google Scholar]
/content/journals/cad/10.2174/0115734099356426241119051916
Loading
Network Pharmacology and In Vivo Experimental Verification of the Mechanism of the Qing'e Pill for Treating Intervertebral Disc Degeneration
Bentham Science Publishers ; https://doi.org/10.2174/0115734099356426241119051916
/content/journals/cad/10.2174/0115734099356426241119051916
/content/journals/cad/10.2174/0115734099356426241119051916
Loading

Data & Media loading...


  • Article Type:     Research Article
Keywords: molecular mechanisms ; Intervertebral disc degeneration ; in vivo experiments ; Qing’e Pill

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test