Please wait a minute...
J Zhejiang Univ (Med Sci)  2020, Vol. 49 Issue (5): 629-636    DOI: 10.3785/j.issn.1008-9292.2020.10.13
    
Effects of antihyperglycemics on endothelial progenitor cells
HAN Xue1,2(),JIANG Guojun2,SHI Qiaojuan1,*()
1. Laboratory Animal Center, Hangzhou Medical College, Hangzhou 310015, China
2. Department of Pharmacy, Zhejiang Xiaoshan Hospital, Hangzhou 311200, China
Download: HTML( 7 )   PDF(1090KB)
Export: BibTeX | EndNote (RIS)      

Abstract  

Endothelial progenitor cells (EPCs) play an important role in diabetic vascular complications. A large number of studies have revealed that some clinical antihyperglycemics can improve the complications of diabetes by regulating the function of EPCs. Metformin can improve EPCs function in diabetic patients by regulating oxidative stress level or downstream signaling pathway of adenosine monophosphate activated protein kinase; Pioglitazone can delay the aging of EPCs by regulating telomerase activity; acarbose, sitagliptin and insulin can promote the proliferation, migration and adhesion of EPCs. In addition to lowering blood glucose, the effects of antihyperglycemics on EPCs may also be one of the mechanisms to improve the complications of diabetes. This article reviews the research progress on the regulation of EPC proliferation and function by antihyperglycemics.



Key wordsDiabetes mellitus      Endothelial progenitor cells      Antihyperglycemics      Oxidative stress      Telomerase      Review     
Received: 25 April 2020      Published: 19 November 2020
CLC:  R587.1  
Corresponding Authors: SHI Qiaojuan     E-mail: 13819113623@163.com;shiqiaojuan@163.com
Cite this article:

HAN Xue,JIANG Guojun,SHI Qiaojuan. Effects of antihyperglycemics on endothelial progenitor cells. J Zhejiang Univ (Med Sci), 2020, 49(5): 629-636.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2020.10.13     OR     http://www.zjujournals.com/med/Y2020/V49/I5/629


降血糖药对内皮祖细胞作用的研究进展

内皮祖细胞(EPC)在糖尿病血管并发症中发挥重要作用。大量研究证明,临床部分降血糖药可通过调节EPC功能进而发挥改善糖尿病并发症的作用。其中二甲双胍可通过多效性调节机体氧化应激水平或AMP活化蛋白激酶下游信号通路改善糖尿病患者的EPC功能;吡格列酮可通过调节端粒酶活性延缓EPC衰老;阿卡波糖、西格列汀和胰岛素在临床研究中均显示出提高EPC活性的作用,其机制主要表现为促进EPC增殖、迁移、黏附等。降血糖药的这种降血糖之外的药理作用可能是改善糖尿病并发症的机制之一。本文在分析EPC对糖尿病并发症血管修复影响的基础上,对降血糖药调控EPC数量和功能的研究进展作一综述。


关键词: 糖尿病,  内皮祖细胞,  降血糖药,  氧化应激,  端粒酶,  综述 
来源 细胞表面标志物 参考文献序号
外周血 CD31、酪氨酸激酶受体2、胎肝激酶1 5-6
骨髓 血管内皮生长因子受体2、CD31, 血管上皮钙黏素、血管性血友病因子 7
胚胎 内皮型一氧化氮合酶、血管内皮生长因子、胎肝激酶1、样酪氨酸激酶、血管上皮钙黏素、CD34、血小板内皮细胞黏附分子1 8-9
脐带血 标记乙酰化低密度脂蛋白、人源血管内皮生长因子受体2(KDR)、血管上皮钙黏素、CD31、血管性血友病因子、CD45 10
人脐静脉内皮细胞 CD133、CD146单克隆抗体(P1H12)、血管内皮生长因子受体2、血小板内皮细胞黏附分子、内皮联蛋白、细胞间黏附分子1 11
Tab 1 Surface markers of endothelial progenitor cells (EPC)
[1]   RIDDY D M , DELERIVE P , SUMMERS R J et al. G Protein-coupled receptors targeting insulin resistance, obesity, and type 2 diabetes mellitus[J]. Pharmacol Rev, 2018, 70 (1): 39- 67
doi: 10.1124/pr.117.014373
[2]   SHAN K , LIU C , LIU B H et al. Circular noncoding RNA HIPK3 mediates retinal vascular dysfunction in diabetes mellitus[J]. Circulation, 2017, 136 (17): 1629- 1642
doi: 10.1161/CIRCULATIONAHA.117.029004
[3]   DAI X, YAN X, ZENG J, et al. Elevating CXCR7 improves angiogenic function of EPCs via Akt/GSK-3β/Fyn-mediated Nrf2 activation in diabetic limb ischemia[J/OL]. Circ Res, 2017, 120(5): e7-e23. DOI: 10.1161/CIRCRESAHA.117.310619.
[4]   CHOI J H , NGUYEN M P , JUNG S Y et al. Inhibitory effect of glyceollins on vasculogenesis through suppression of endothelial progenitor cell function[J]. Mol Nutr Food Res, 2013, 57 (10): 1762- 1771
doi: 10.1002/mnfr.201200826
[5]   ITO C , KUMAGAI M , MANABE A et al. Hyperdiploid acute lymphoblastic leukemia with 51 to 65 chromosomes:a distinct biological entity with a marked propensity to undergo apoptosis[J]. Blood, 1999, 93 (1): 315- 320
doi: 10.1182/blood.V93.1.315
[6]   HILL J M , ZALOS G , HALCOX J P et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk[J]. N Engl J Med, 2003, 348 (7): 593- 600
doi: 10.1056/NEJMoa022287
[7]   HRISTOV M , ERL W , WEBER P C . Endothelial progenitor cells:isolation and characterization[J]. Trends Cardiovasc Med, 2003, 13 (5): 201- 206
doi: 10.1016/s1050-1738(03)00077-x
[8]   MCCLOSKEY K E , SMITH D A , JO H et al. Embryonic stem cell-derived endothelial cells may lack complete functional maturation in vitro[J]. J Vasc Res, 2006, 43 (5): 411- 421
doi: 10.1159/000094791
[9]   GLASER R , PEACOCK W F , WU A H et al. Placental growth factor and B-type natriuretic peptide as independent predictors of risk from a multibiomarker panel in suspected acute coronary syndrome (Acute Risk and Related Outcomes Assessed With Cardiac Biomarkers[ARROW]) study[J]. Am J Cardiol, 2011, 107 (6): 821- 826
doi: 10.1016/j.amjcard.2010.11.003
[10]   MUROHARA T , IKEDA H , DUAN J et al. Transplanted cord blood-derived endothelial precursor cells augment postnatal neovascularization[J]. J Clin Invest, 2000, 105 (11): 1527- 1536
doi: 10.1172/JCI8296
[11]   BAGLEY R G , WALTER-YOHRLING J , CAO X et al. Endothelial precursor cells as a model of tumor endothelium:characterization and comparison with mature endothelial cells[J]. Cancer Res, 2003, 63 (18): 5866- 5873
[12]   THUM T , FRACCAROLLO D , SCHULTHEISS M et al. Endothelial nitric oxide synthase uncoupling impairs endothelial progenitor cell mobilization and function in diabetes[J]. Diabetes, 2007, 56 (3): 666- 674
doi: 10.2337/db06-0699
[13]   SCHALKWIJK C G , STEHOUWER C D . Vascular complications in diabetes mellitus:the role of endothelial dysfunction[J]. Clin Sci (Lond), 2005, 109 (2): 143- 159
doi: 10.1042/CS20050025
[14]   FADINI G P , SARTORE S , ALBIERO M et al. Number and function of endothelial progenitor cells as a marker of severity for diabetic vasculopathy[J]. Arterioscler Thromb Vasc Biol, 2006, 26 (9): 2140- 2146
doi: 10.1161/01.ATV.0000237750.44469.88
[15]   YU J W , DENG Y P , HAN X et al. Metformin improves the angiogenic functions of endothelial progenitor cells via activating AMPK/eNOS pathway in diabetic mice[J]. Cardiovasc Diabetol, 2016, 15 88
doi: 10.1186/s12933-016-0408-3
[16]   HAN X , TAO Y , DENG Y et al. Metformin accelerates wound healing in type 2 diabetic db/db mice[J]. Mol Med Rep, 2017, 16 (6): 8691- 8698
doi: 10.3892/mmr.2017.7707
[17]   SPIGONI V, PICCONI A, CITO M, et al. Pioglitazone improves in vitro viability and function of endothelial progenitor cells from individuals with impaired glucose tolerance[J/OL]. PLoS One, 2012, 7(11): e48283. DOI: 10.1371/journal.pone.0048283.
[18]   HAN X , DENG Y , YU J et al. Acarbose accelerates wound healing via Akt/eNOS signaling in db/db Mice[J]. Oxid Med Cell Longev, 2017, 2017 7809581
doi: 10.1155/2017/7809581
[19]   DONG L , KANG L , DING L et al. Insulin modulates ischemia-induced endothelial progenitor cell mobilization and neovascularization in diabetic mice[J]. Microvasc Res, 2011, 82 (3): 227- 236
doi: 10.1016/j.mvr.2011.09.006
[20]   ZHANG H F , WANG L , YUAN H J et al. PPAR-γ agonist pioglitazone prevents apoptosis of endothelial progenitor cells from rat bone marrow[J]. Cell Biol Int, 2013, 37 (5): 430- 435
doi: 10.1002/cbin.10046
[21]   GHOSH S , LAKSHMANAN A P , HWANG M J et al. Metformin improves endothelial function in aortic tissue and microvascular endothelial cells subjected to diabetic hyperglycaemic conditions[J]. Biochem Pharmacol, 2015, 98 (3): 412- 421
doi: 10.1016/j.bcp.2015.10.008
[22]   HATTORI Y , HATTORI K , HAYASHI T . Pleiotropic benefits of metformin:macrophage targeting its anti-inflammatory mechanisms[J]. Diabetes, 2015, 64 (6): 1907- 1909
doi: 10.2337/db15-0090
[23]   LIAO Y F , CHEN L L , ZENG T S et al. Number of circulating endothelial progenitor cells as a marker of vascular endothelial function for type 2 diabetes[J]. Vasc Med, 2010, 15 (4): 279- 285
doi: 10.1177/1358863X10367537
[24]   CHEN L L , LIAO Y F , ZENG T S et al. Effects of metformin plus gliclazide compared with metformin alone on circulating endothelial progenitor cell in type 2 diabetic patients[J]. Endocrine, 2010, 38 (2): 266- 275
doi: 10.1007/s12020-010-9383-8
[25]   AMBASTA R K , KOHLI H , KUMAR P . Multiple therapeutic effect of endothelial progenitor cell regulated by drugs in diabetes and diabetes related disorder[J]. J Transl Med, 2017, 15 (1): 185
doi: 10.1186/s12967-017-1280-y
[26]   WU N , GU H J , LI Q . Effects of antidiabetic drug metformin on the migration and invasion abilities of human pulmonary adenocarcinoma A549 cell line in vitro[J]. J Thorac Dis, 2010, 2 (2): 76- 80
[27]   CHEN X , HU C , ZHANG W et al. Metformin inhibits the proliferation, metastasis, and cancer stem-like sphere formation in osteosarcoma MG63 cells in vitro[J]. Tumour Biol, 2015, 36 (12): 9873- 9883
doi: 10.1007/s13277-015-3751-1
[28]   DORMANDY J A , CHARBONNEL B , ECKLAND D J et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events):a randomised controlled trial[J]. Lancet, 2005, 366 (9493): 1279- 1289
doi: 10.1016/S0140-6736(05)67528-9
[29]   RUIZ E , REDONDO S , GORDILLO-MOSCOSO A et al. EPCs adhesion to arteries from diabetic and non-diabetic patients:effect of pioglitazone[J]. Front Biosci (Landmark Ed), 2009, 14 (1): 3608- 3618
doi: 10.2741/3475
[30]   WANG C H, TING M K, VERMA S, et al. Pioglitazone increases the numbers and improves the functional capacity of endothelial progenitor cells in patients with diabetes mellitus[J/OL]. Am Heart J, 2006, 152(6): 1051.e1-e8. DOI: 10.1016/j.ahj.2006.07.029.
[31]   MINAMINO T , MIYAUCHI H , YOSHIDA T et al. Endothelial cell senescence in human atherosclerosis:role of telomere in endothelial dysfunction[J]. Circulation, 2002, 105 (13): 1541- 1544
doi: 10.1161/01.cir.0000013836.85741.17
[32]   VAN DER HARST P , VAN DER STEEGE G , DE BOER R A et al. Telomere length of circulating leukocytes is decreased in patients with chronic heart failure[J]. J Am Coll Cardiol, 2007, 49 (13): 1459- 1464
doi: 10.1016/j.jacc.2007.01.027
[33]   MINAMINO T , KOMURO I . Role of telomeres in vascular senescence[J]. Front Biosci, 2008, 13 2971- 2979
doi: 10.2741/2902
[34]   ASSMUS B , URBICH C , AICHER A et al. HMG-CoA reductase inhibitors reduce senescence and increase proliferation of endothelial progenitor cells via regulation of cell cycle regulatory genes[J]. Circ Res, 2003, 92 (9): 1049- 1055
doi: 10.1161/01.RES.0000070067.64040.7C
[35]   RUDOLPH K L , CHANG S , LEE H W et al. Longevity, stress response, and cancer in aging telomerase-deficient mice[J]. Cell, 1999, 96 (5): 701- 712
doi: 10.1016/s0092-8674(00)80580-2
[36]   IMANISHI T , HANO T , SAWAMURA T et al. Oxidized low-density lipoprotein induces endothelial progenitor cell senescence, leading to cellular dysfunction[J]. Clin Exp Pharmacol Physiol, 2004, 31 (7): 407- 413
doi: 10.1111/j.1440-1681.2004.04022.x
[37]   KURZ D J , DECARY S , HONG Y et al. Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells[J]. J Cell Sci, 2004, 117 (Pt 11): 2417- 2426
doi: 10.1242/jcs.01097
[38]   FUJII H , LI S H , SZMITKO P E et al. C-reactive protein alters antioxidant defenses and promotes apoptosis in endothelial progenitor cells[J]. Arterioscler Thromb Vasc Biol, 2006, 26 (11): 2476- 2482
doi: 10.1161/01.ATV.0000242794.65541.02
[39]   MURASAWA S , LLEVADOT J , SILVER M et al. Constitutive human telomerase reverse transcriptase expression enhances regenerative properties of endothelial progenitor cells[J]. Circulation, 2002, 106 (9): 1133- 1139
doi: 10.1161/01.cir.0000027584.85865.b4
[40]   IMANISHI T , KOBAYASHI K , KUROI A et al. Pioglitazone inhibits angiotensin II-induced senescence of endothelial progenitor cell[J]. Hypertens Res, 2008, 31 (4): 757- 765
doi: 10.1291/hypres.31.757
[41]   ZHENG M Y , YANG J H , SHAN C Y et al. Effects of 24-week treatment with acarbose on glucagon-like peptide 1 in newly diagnosed type 2 diabetic patients:a preliminary report[J]. Cardiovasc Diabetol, 2013, 12 73
doi: 10.1186/1475-2840-12-73
[42]   NAKAMURA K , OE H , KIHARA H et al. DPP-4 inhibitor and alpha-glucosidase inhibitor equally improve endothelial function in patients with type 2 diabetes:EDGE study[J]. Cardiovasc Diabetol, 2014, 13 110
doi: 10.1186/s12933-014-0110-2
[43]   KEATING G M . Vildagliptin:a review of its use in type 2 diabetes mellitus[J]. Drugs, 2010, 70 (16): 2089- 2112
doi: 10.2165/11206370-000000000-00000
[44]   FADINI G P , BOSCARO E , ALBIERO M et al. The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes:possible role of stromal-derived factor-1alpha[J]. Diabetes Care, 2010, 33 (7): 1607- 1609
doi: 10.2337/dc10-0187
[45]   ASO Y , JOJIMA T , IIJIMA T et al. Sitagliptin, a dipeptidyl peptidase-4 inhibitor, increases the number of circulating CD34+ CXCR4+ cells in patients with type 2 diabetes[J]. Endocrine, 2015, 50 (3): 659- 664
doi: 10.1007/s12020-015-0688-5
[46]   DEI CAS A , SPIGONI V , CITO M et al. Vildagliptin, but not glibenclamide, increases circulating endothelial progenitor cell number:a 12-month randomized controlled trial in patients with type 2 diabetes[J]. Cardiovasc Diabetol, 2017, 16 (1): 27
doi: 10.1186/s12933-017-0503-0
[47]   FADINI G P , BONORA B M , CAPPELLARI R et al. Acute effects of linagliptin on progenitor cells, monocyte phenotypes, and soluble mediators in type 2 diabetes[J]. J Clin Endocrinol Metab, 2016, 101 (2): 748- 756
doi: 10.1210/jc.2015-3716
[48]   FADINI G P , DE KREUTZENBERG S V , MARIANO V et al. Optimized glycaemic control achieved with add-on basal insulin therapy improves indexes of endothelial damage and regeneration in type 2 diabetic patients with macroangiopathy:a randomized crossover trial comparing detemir versus glargine[J]. Diabetes Obes Metab, 2011, 13 (8): 718- 725
doi: 10.1111/j.1463-1326.2011.01396.x
[49]   OIKONOMOU D , KOPF S , VON BAUER R et al. Influence of insulin and glargine on outgrowth and number of circulating endothelial progenitor cells in type 2 diabetes patients:a partially double-blind, randomized, three-arm unicenter study[J]. Cardiovasc Diabetol, 2014, 13 137
doi: 10.1186/s12933-014-0137-4
[50]   HUMPERT P M , NEUWIRTH R , BATTISTA M J et al. SDF-1 genotype influences insulin-dependent mobilization of adult progenitor cells in type 2 diabetes[J]. Diabetes Care, 2005, 28 (4): 934- 936
doi: 10.2337/diacare.28.4.934
[51]   杨吉锋, 陶松桔, 张亚萍 et al. 短期胰岛素泵强化治疗对初诊T2DM患者循环内皮祖细胞水平的影响及其抗炎机制[J]. 中国临床研究, 2011, 24 (8): 666- 668
YANG Jifeng , TAO Songju , ZHANG Yaping et al. Effect of short-term intensive treatment with insulin pump on the level of circulating endothelial progenitor cells in patients with newly diagnosed type 2 diabetes and its anti-inflammatory mechanism[J]. Chinese Journal of Clinical Research, 2011, 24 (8): 666- 668
[52]   CHEN Y , ZHANG X , HE J et al. Delayed administration of the glucagon-like peptide 1 analog liraglutide promoting angiogenesis after focal cerebral ischemia in mice[J]. J Stroke Cerebrovasc Dis, 2018, 27 (5): 1318- 1325
doi: 10.1016/j.jstrokecerebrovasdis.2017.12.015
[53]   ZITMAN-GAL T , EINBINDER Y , OHANA M et al. Effect of liraglutide on the Janus kinase/signal transducer and transcription activator (JAK/STAT) pathway in diabetic kidney disease in db/db mice and in cultured endothelial cells[J]. J Diabetes, 2019, 11 (8): 656- 664
doi: 10.1111/1753-0407.12891
[54]   李彩林, 雅军, 郭立新 . 利拉鲁肽对瘦素受体缺陷大鼠主动脉内皮细胞的保护作用及机制[J]. 中华糖尿病杂志, 2017, 9 (9): 567- 572
LI Cailin , YA Jun , GUO Lixin . Protective effect and mechanism of liraglutide on aorta endothelial cells in Zucker diabetic fatty rats[J]. Chinese Journal of Diabetes Mellitus, 2017, 9 (9): 567- 572
doi: 10.3760/cma.j.issn.1674-5809.2017.09.007
[55]   李虎, 束庆, 杨贤 et al. 利拉鲁肽对高糖诱导的人脐静脉内皮细胞与单核细胞黏附的影响及作用机制[J]. 中国医师杂志, 2019, 21 (6): 830- 834, 839
LI Hu , SHU Qing , YANG Xian et al. Liraglutide prevents high glucose-induced adhesion of endothelial cells to monocyte by targeting IKK-NF-κB[J]. Journal of Chinese Physician, 2019, 21 (6): 830- 834, 839
doi: 10.3760/cma.j.issn.1008-1372.2019.06.008
[56]   DALAMA B , MESA J . New oral hypoglycemic agents and cardiovascular risk. Crossing the metabolic border[J]. Rev Esp Cardiol (Engl Ed), 2017, 70 (4): 309
doi: 10.1016/j.rec.2016.11.034
[57]   SCHNELL O, VALENSI P, STANDL E, et al. Comparison of mechanisms and transferability of outcomes of SGLT2 inhibition between type 1 and type 2 diabetes[J/OL]. Endocrinol Diabetes Metab, 2020, 3(3): e00129. DOI: 10.1002/edm2.129.
[58]   GASPARI T , SPIZZO I , LIU H et al. Dapagliflozin attenuates human vascular endothelial cell activation and induces vasorelaxation:a potential mechanism for inhibition of atherogenesis[J]. Diab Vasc Dis Res, 2018, 15 (1): 64- 73
doi: 10.1177/1479164117733626
[1] LI Mengyao,LIU Pan,KE Yuehai,ZHANG Xue. Research progress on macrophage in radiation induced lung injury[J]. J Zhejiang Univ (Med Sci), 2020, 49(5): 623-628.
[2] DUAN Runping, XU Yesheng, ZHENG Libin, YAO Yufeng. Research progress on etiologic diagnosis of ocular viral diseases[J]. J Zhejiang Univ (Med Sci), 2020, 49(5): 644-650.
[3] WU Wei,XU Jian. Research progress on the role of pentraxin 3 in polycystic ovary syndrome[J]. J Zhejiang Univ (Med Sci), 2020, 49(5): 637-643.
[4] XU Qinglin,LOU Guodong,WANG Tiantian,ZHANG Lisan. Advances in treatment of narcolepsy[J]. J Zhejiang Univ (Med Sci), 2020, 49(4): 419-424.
[5] JIANG Peiran,WANG Zhiping. Progress on axon regeneration in model organisms[J]. J Zhejiang Univ (Med Sci), 2020, 49(4): 500-507.
[6] CHEN Junyi,YANG Xiang,FANG Xuexian,WANG Fudi,MIN Junxia. The role of ferroptosis in chronic diseases[J]. J Zhejiang Univ (Med Sci), 2020, 49(1): 44-57.
[7] YU Qing, XIONG Xiufang, SUN Yi. Targeting Cullin-RING E3 ligases for anti-cancer therapy: efforts on drug discovery[J]. J Zhejiang Univ (Med Sci), 2020, 49(1): 1-19.
[8] DUAN Lingyan,YIN Xiangju,MENG Hong'en,FANG Xuexian,MIN Junxia,WANG Fudi. Progress on epigenetic regulation of iron homeostasis[J]. J Zhejiang Univ (Med Sci), 2020, 49(1): 58-70.
[9] LI Ai,ZHANG Tianyuan,GAO Jianqing. Progress on utilizing mesenchymal stem cells as cellular delivery system for targeting delivery of as drug/gene for anti-tumor therapy[J]. J Zhejiang Univ (Med Sci), 2020, 49(1): 20-34.
[10] HUANG Yaoping,YANG Feng,ZHOU Tianhua,XIE Shanshan. Emerging roles of Hippo signaling pathway in gastrointestinal cancers and its molecular mechanisms[J]. J Zhejiang Univ (Med Sci), 2020, 49(1): 35-43.
[11] ZHONG Wen,LOU Yan,QIU Chenyang,LI Donglin,ZHANG Hongkun. Antithrombotic therapy after iliac vein stenting[J]. J Zhejiang Univ (Med Sci), 2020, 49(1): 131-136.
[12] XU Yiming,YING Kejing. Research progress on neutrophil extracellular traps in tumor[J]. J Zhejiang Univ (Med Sci), 2020, 49(1): 107-112.
[13] LIU Xiaoxiao,GUO Liqiong,LIANG Cheng. Research progress on electroencephalogram characteristics of anti-N-methyl-D-aspartate receptor encephalitis[J]. J Zhejiang Univ (Med Sci), 2020, 49(1): 118-123.
[14] FANG Juan,PAN Zhicheng,GUO Xiaogang. Research advance of ANRIL on atherosclerosis by regulating cell proliferation and apoptosis[J]. J Zhejiang Univ (Med Sci), 2020, 49(1): 113-117.
[15] WANG Shiying,GU Xinhua. Progress on clinical application of orthodontic-implant combined therapy[J]. J Zhejiang Univ (Med Sci), 2020, 49(1): 124-130.