CX3CL1和CX3CR1与动脉粥样硬化性心脏病损伤机制的研究现状

doi:10.3969/j.issn.1673-8640.2016.011.017

摘要/Abstract

摘要：

趋化因子Fractalkine（CX3CL1）及其特异性受体CX3C趋化因子受体1（CX3CR1）、CX3CL1-CX3CR1轴均参与了动脉粥样硬化的形成和发展,并改变了斑块成分和斑块的稳定性。CX3CR1 V249I和CX3CR1 T280M与冠状动脉损伤相关。在动脉粥样硬化斑块中,CX3CL1、CX3CR1通过血管平滑肌细胞（VSMC）和单核细胞/巨噬细胞进行表达,VSMC和单核细胞间相互作用需通过CX3CL1-CX3CR1轴,这种相互作用调节了单核细胞的生存及分化。抵抗素可能通过一系列涉及核因子-κB（NF-κB）、活化蛋白-1（AP-1）、信号转导和转录激活因子（STAT）1/STAT3的机制使CX3CL1和CX3CR1表达上调,进而产生平滑肌细胞的促炎性状态。在不稳定性冠心病及冠状动脉严重病变患者中,血清CX3CL1水平明显升高;血清CX3CR1在冠状动脉狭窄性疾病患者中明显升高,但与冠状动脉狭窄程度无相关性。通过CX3CL1/CX3CR1的相关研究,可揭示某些炎性介质在动脉粥样硬化性心脏病中的潜在机制和致病作用,从而为临床治疗策略及干预药物的研究提供依据及方向。

关键词: Fractalkine, CX3C趋化因子受体1, 动脉粥样硬化, 冠心病, 单核细胞

Abstract:

Fractalkine（CX3CL1） and its specific receptor CX3C chemokine receptor1（CX3CR1）,CX3CL1-CX3CR1 axis are all involved in the formation and development of atherosclerosis,which change the plaque composition and stability of plaques. CX3CR1 V249I and CX3CR1 T280M are associated with coronary artery lesions. In atherosclerotic plaque,CX3CL1 and CX3CR1 were expressed by vascular smooth muscle cells（VSMC） and monocytes/macrophages. Interaction between vascular smooth muscle cells（VSMC） and monocyte needs CX3CL1-CX3CR1 axis,and this mutual effect regulates the survival and differentiation of monocyte. Through a series of mechanism,such as involved nuclear factor-kappa B（NF-κB）,activated protein-1（AP-1） and signal transducers and activators of transcription（STAT） 1/STAT3,resistin up-regulates the expressions of CX3CL1 and CX3CR1,and generates pro-inflammatory state of smooth muscle cells. Serum CX3CL1 level is increased in patients with unstable coronary artery diseases and patients with severe coronary artery lesions. Serum CX3CR1 level is increased in patients with coronary artery stenosis,which is not associated with the degree of coronary artery stenosis. The related study on CX3CL1/CX3CR1 shows the potential mechanism and pathogenicity effect of some inflammatory mediators in atherosclerotic heart diseases,so as to provide a reference for clinical treatment strategies and drug intervention studies.

Key words: Fractalkine, CX3C chemokine receptor 1, Atherosclerosis, Coronary artery diseases, Monocytes

中图分类号:

R446.1

李永姝, 张宝欢, 贾克刚, 刘军锋. CX3CL1和CX3CR1与动脉粥样硬化性心脏病损伤机制的研究现状[J]. 检验医学, 2016, 31(11): 1002-1010.

LI Yongshu, ZHANG Baohuan, JIA Kegang, LIU Junfeng. CX3CL1 and CX3CR1 in lesion mechanism of atherosclerotic heart diseases[J]. Laboratory Medicine, 2016, 31(11): 1002-1010.

图/表 3

参考文献 51

1	赵琰枫,冯晓燕,张贺秋. RANTES和Eotaxin与结核病[J]. 检验医学,2015,30(10):1048-1052.
2	WHITE GE,GREAVES DR.Fractalkine:a survivor's guide:chemokines as antiapoptotic mediators[J]. Arterioscler Thromb Vasc Biol,2012,32(3):589-594.
3	APOSTOLAKIS S,SPANDIDOS D.Chemokines and atherosclerosis:focus on the CX3CL1/CX3CR1 pathway[J]. Acta Pharmacol Sin,2013,34(10):1251-1256.
4	FLIERL U,BAUERSACHS J,SCHFER A.Modulation of platelet and monocyte function by the chemokine fractalkine(CX3 CL1) in cardiovascular disease[J]. Eur J Clin Invest,2015,45(6):624-633.
5	KUMAR AH,MARTIN K,TURNER EC,et al.Role of CX3CR1 receptor in monocyte/macrophage driven neovascularization[J]. PLoS One,2013,8(2):e57230.
6	FLIERL U,SCHFER A.Fractalkine-a local inflammatory marker aggravating platelet activation at the vulnerable plaque[J]. Thromb Haemost,2012,108(3):457-463.
7	ESCHER F,VETTER R,KÜHL U,et al. Fractalkine in human inflammatory cardiomyopathy[J]. Heart,2011,97(9):733-739.
8	POUPEL L,COMBADIERE C.Atherosclerosis:on the trail of chemokines[J]. Biol Aujourdhui,2010,204(4):285-293.
9	石磊,孙鲁宁,顾鹏毅,等. 趋化因子受体CX3CR1基因多态与中国北方人群脑梗死的关系[J]. 中风与神经疾病杂志,2012,29(5):434-438.
10	肖宏凯,陈柏荣,黄茵,等. CX3CR1基因249V/I 多态性与早发冠心病及血脂比值的相关性[J]. 中国动脉硬化杂志,2014,22(8):827-830.
11	WU J,YIN RX,LIN QZ,et al.Two polymorphisms in the Fractalkine receptor CX3CR1 gene influence the development of atherosclerosis:a meta-analysis[J]. Dis Markers,2014,2014:913678.
12	MORGAN TM,XIAO L,LYONS P,et al.Investigation of 89 candidate gene variants for effects on all-cause mortality following acute coronary syndrome[J]. BMC Med Genet,2008,9:66.
13	MATZHOLD EM,TRUMMER O,GRÜNBACHER G,et al. Association of polymorphisms in the chemokine receptor CX3CR1 gene with coronary artery disease[J]. Cytokine,2009,47(3):224-227.
14	肖宏凯,金莉子,谢桂庭,等. CX3CR1基因多态性与冠心病的相关性[J]. 中国动脉硬化杂志,2010,18(12):993-995.
15	SINGH N,RAI H,SINHA N,et al.Association of V249I and T280M polymorphisms in the chemokine receptor CX3CR1 gene with early onset of coronary artery disease among North Indians[J]. Genet Test Mol Biomarkers,2012,16(7):756-760.
16	SINGH N,SINHA N,KUMAR S,et al.Polymorphism in chemokine receptor genes and risk of acute myocardial infarction in North Indian population[J]. Mol Biol Rep,2012,39(3):2753-2759.
17	PUCCI S,MAZZRELLI P,ZONETTI MJ,et al.CX3CR1 receptor polymorphisms,Th1 cell recruitment,and acute myocardial infarction outcome:looking for a link[J]. Biomed Res Int,2013,2013:451349.
18	冯皓,郭葆玉. 趋化因子受体CX3CR1的分子结构及生物学功能[J]. 国外医学(分子生物学分册),2002,24(6):378-380.
19	NASIBULLIN TR,YAGAFAROVA LF,YAGAFAROV IR,et al.Combinations of polymorphic markers of chemokine genes,their receptors and acute phase protein genes as potential predictors of coronary heart diseases[J]. Acta Naturae,2016,8(1):111-116.
20	GOLBUS JR,STITZIEL NO,ZHAO W,et al.Common and rare genetic variation in CCR2,CCR5,or CX3CR1 and risk of atherosclerotic coronary heart disease and glucometabolic traits[J]. Circ Cardiovasc Genet,2016. [Epub ahead of print]
21	STOLLA M,PELISEK J,VON BRÜHL ML,et al. Fractalkine is expressed in early and advanced atherosclerotic lesions and supports monocyte recruitment via CX3CR1[J]. PLoS One,2012,7(8):e43572.
22	WHITE GE,MCNEILL E,CHANNON KM,et al.Fractalkine promotes human monocyte survival via a reduction in oxidative stress[J]. Arterioscler Thromb Vasc Biol,2014,34(12):2554-2562.
23	LIU Y,IMANISHI T,IKEJIMA H,et al.Association between circulating monocyte subsets and in-stent restenosis after coronary stent implantation in patients with ST-elevation myocardial infarction[J]. Circ J,2010,74(12):2585-2591.
24	FONOVIC UP,JEVNIKAR Z,KOS J.Cathepsin S generates soluble CX3CL1(fractalkine) in vascular smooth muscle cells[J]. Biol Chem,2013,394(10):1349-1352.
25	HERLEA-PANA O,YAO L,HEUSER-BAKER J,et al.Chemokine receptors CXCR2 and CX3CR1 differentially regulate functional responses of bone-marrow endothelial progenitors during atherosclerotic plaque regression[J]. Cardiovasc Res,2015,106(2):324-337.
26	SHAH R,MATTHEWS GJ,SHAH RY,et al.Serum fractalkine(CX3CL1) and cardiovascular outcomes and diabetes:findings from the chronic renal insufficiency cohort(CRIC) study[J]. Am J Kidney Dis,2015,66(2): 266-273.
27	MARTYNOWICZ H,JANUS A,NOWACKI D,et al.The role of chemokines in hypertension[J]. Adv Clin Exp Med,2014,23(3):319-325.
28	WHITE GE,TAN TC,JOHN AE,et al.Fractalkine has anti-apoptotic and proliferative effects on human vascular smooth muscle cells via epidermal growth factor receptor signalling[J]. Cardiovasc Res,2010,85(4):825-835.
29	金元哲,雷明明,颜冰,等. 趋化因子FKN对人外周血单个核细胞IL-8表达的影响及ERK、PI3K和NF-κB在其中的作用[J]. 大连医科大学学报,2014,43(2):124-128.
30	SZUKIEWICZ D,WOJCIECHOWSKA M,BILSKA A,et al.Aspirin action in endothelial cells:different patterns of response between chemokine CX3CL1/CX3CR1 and TNF-α/TNFR1 signaling pathways[J]. Cardiovasc Drugs Ther,2015,29(3):219-229.
31	ZHOU R,GONG AY,CHEN D,et al.Histone deacetylases and NF-κB signaling coordinate expression of CX3CL1 in epithelial cells in response to microbial challenge by suppressing miR-424 and miR-503[J]. PLoS One,2013,8(5):e65153.
32	阿曼古丽·如则,赵一蔚,古力热巴·夏依买旦,等. p38抑制剂对低剪切应力诱导的人脐静脉内皮细胞株Fractalkine蛋白表达的影响[J]. 新疆医科大学学报,2016,39(3):293-297.
33	GREENE JA,PORTILLO JA,LOPEZ CORCINO Y,et al.CD40-TRAF signaling upregulates CX3CL1 and TNF-α in human aortic endothelial cells but not in retinal endothelial cells[J]. PLoS One,2015,10(12):e0144133.
34	ZHANG H,GOU C,WU D,et al.Hydrogen sulfide inhibits the development of atherosclerosis with suppressing CX3CR1 and CX3CL1 expression[J]. PLoS One,2012,7(7):e41147.
35	ZHANG H,GUO C,ZHANG A,et al.Effect of S-aspirin,a novel hydrogen-sulfide-releasing aspirin(ACS14),on atherosclerosis in apoE-deficient mice[J]. Eur J Pharmacol,2012,697(1-3):106-116.
36	GAN AM,BUTOI ED,MANEA A,et al.Inflammatory effects of resistin on human smooth muscle cells:up-regulation of fractalkine and its receptor,CX3CR1 expression by TLR4 and Gi-protein pathways[J]. Cell Tissue Res,2013,351(1):161-174.
37	MARTINEZ-HERVÁS S,VINUÉ A,NÚEZ L,et al. Insulin resistance aggravates atherosclerosis by reducing vascular smooth muscle cell survival and increasing CX3CL1/CX3CR1 axis[J]. Cardiovasc Res,2014,103(2):324-336.
38	PIRVULESCU MM,GAN AM,STAN D,et al.Subendothelial resistin enhances monocyte transmigration in a co-culture of human endothelial and smooth muscle cells by mechanisms involving fractalkine,MCP-1 and activation of TLR4 and Gi/o proteins signaling[J]. Int J Biochem Cell Biol,2014,50:29-37.
39	POUPEL L,BOISSONNAS A,HERMAND P,et al.Pharmacological inhibition of the chemokine receptor,CX3CR1,reduces atherosclerosis in mice[J]. Arterioscler Thromb Vasc Biol,2013 ,33(10):2297-2305.
40	张阿莲,高霖,程纯,等. 硫化氢对动脉粥样硬化的影响及其与CX3CR1的关系[J]. 中国分子心脏病学杂志,2014,14(1):839-844.
41	CIMATO TR,PALKA BA.Fractalkine(CX3CL1),GM-CSF and VEGF-a levels are reduced by statins in adult patients[J]. Clin Transl Med,2014,3:14.
42	NIE P,LI D,HU L,et al.Atorvastatin improves plaque stability in ApoE-knockout mice by regulating chemokines and chemokine receptors[J]. PLoS One,2014,9(5):e97009.
43	彭丹丹,邱健. 瑞舒伐他汀对冠心病患者CX3CR1表达的影响[J]. 广州医学院学报,2014,42(2):8-10.
44	ALI MT,MARTIN K,KUMAR AH,et al.A novel CX3CR1 antagonist eluting stent reduces stenosis by targeting inflammation[J]. Biomaterials,2015,69:22-29.
45	XUEYAO Y,SAIFEI Z,DAN Y,et al.Circulating fractalkine levels predict the development of the metabolic syndrome[J]. Int J Endocrinol,2014,2014:715148.
46	SHAH R,MATTHEWS GJ,SHAH RY,et al.Serum fractalkine(CX3CL1) and cardiovascular outcomes and diabetes:findings from the chronic renal insufficiency cohort(CRIC) study[J]. Am J Kidney Dis,2015,66(2):266-273.
47	NJERVE IU,PETTERSEN A,OPSTAD TB,et al.Fractalkine and its receptor(CX3CR1) in patients with stable coronary artery disease and diabetes mellitus[J]. Metab Syndr Relat Disord,2012,10(6):400-406.
48	ZHONG ZX,LI B,LI CR,et al.Role of chemokines in promoting instability of coronary atherosclerotic plaques and the underlying molecular mechanism[J]. Braz J Med Biol Res,2015,48(2):161-166.
49	刘君,雷明明,王妍,等. FKN在急性心肌梗死早期诊断中的作用[J]. 中国医科大学学报,2015,44(4):307-310.
50	NJERVE IU,SOLHEIM S,LUNDE K,et al.Fractalkine levels are elevated early after PCI-treated ST-elevation myocardial infarction; no influence of autologous bone marrow derived stem cell injection[J]. Cytokine,2014,69(1):131-135.
51	刘军锋,李旭,贾克刚,等. LOX-1和CX3CR1与冠状动脉狭窄性疾病关系及其预后价值的探讨[J]. 中华检验医学杂志,2014,37(1):66-71.

参考文献	发表年份	国家	样本量（病例/对照）	基因型（病例/对照）			等位基因（病例/对照）		疾病
参考文献	发表年份	国家	样本量（病例/对照）	VV	VI	II	V	I	疾病
[11]	2001	法国	151/249	97/126	47/104	7/19	241/356	61/142	CAD
[11]	2005	奥地利	720/432	395/246	271/161	54/25	1 061/653	379/211	CAD
[11]	2007	希腊	210/165	111/86	81/59	18/20	303/231	117/99	CAD
[12]	2007	美国	802/658	410/353	336/254	56/51	1 156/960	448/356	ACS
[11]	2008	中国	108/80	70/41	33/34	5/5	173/116	43/44	CAD
[11]	2008	加拿大	149/149	73/63	63/69	13/17	209/195	89/103	CAD
[11]	2008	加拿大	150/149	58/63	77/69	15/17	193/195	107/103	CAD
[13]	2009	奥地利	2 565/728	1 374/372	1 012/283	179/73	3 760/1 027	1 370/429	CAD
[14]	2010	中国	139/90	126/68	13/19	0/3	265/155	13/25	CAD
[15]	2012	印度	152/300	111/150	37/118	4/32	259/418	45/182	CAD
[15]	2012	印度	156/300	96/150	48/118	12/32	240/418	72/182	CAD
[16]	2012	印度	230/300	157/150	61/118	12/32	375/418	85/182	AMI
[17]	2013	意大利	25/22	13/2	10/12	2/8	36/16	14/28	AMI
[17]	2013	意大利	16/22	1/2	10/12	5/8	12/16	20/28	AMI

参考文献	发表年份	国家	样本量（病例/对照）	基因型（病例/对照）			等位基因（病例/对照）		疾病
参考文献	发表年份	国家	样本量（病例/对照）	VV	VI	II	V	I	疾病
[11]	2001	法国	151/249	97/126	47/104	7/19	241/356	61/142	CAD
[11]	2005	奥地利	720/432	395/246	271/161	54/25	1 061/653	379/211	CAD
[11]	2007	希腊	210/165	111/86	81/59	18/20	303/231	117/99	CAD
[12]	2007	美国	802/658	410/353	336/254	56/51	1 156/960	448/356	ACS
[11]	2008	中国	108/80	70/41	33/34	5/5	173/116	43/44	CAD
[11]	2008	加拿大	149/149	73/63	63/69	13/17	209/195	89/103	CAD
[11]	2008	加拿大	150/149	58/63	77/69	15/17	193/195	107/103	CAD
[13]	2009	奥地利	2 565/728	1 374/372	1 012/283	179/73	3 760/1 027	1 370/429	CAD
[14]	2010	中国	139/90	126/68	13/19	0/3	265/155	13/25	CAD
[15]	2012	印度	152/300	111/150	37/118	4/32	259/418	45/182	CAD
[15]	2012	印度	156/300	96/150	48/118	12/32	240/418	72/182	CAD
[16]	2012	印度	230/300	157/150	61/118	12/32	375/418	85/182	AMI
[17]	2013	意大利	25/22	13/2	10/12	2/8	36/16	14/28	AMI
[17]	2013	意大利	16/22	1/2	10/12	5/8	12/16	20/28	AMI

参考文献	发表年份	国家	样本量（病例/对照）	基因型（病例/对照）			等位基因（病例/对照）		疾病
参考文献	发表年份	国家	样本量（病例/对照）	TT	TM	MM	T	M	疾病
[11]	2001	法国	151/249	123/179	25/65	3/5	271/423	31/75	CAD
[11]	2005	奥地利	720/432	514/319	189/100	17/13	1 217/738	223/126	CAD
[11]	2007	希腊	210/165	159/109	48/53	3/3	366/271	54/59	CAD
[12]	2007	美国	806/655	565/447	223/195	18/13	1 148/1 089	259/221	ACS
[11]	2008	中国	108/80	88/59	18/20	2/1	194/138	22/22	CAD
[11]	2008	加拿大	149/149	97/94	49/48	3/7	243/236	55/62	CAD
[11]	2008	加拿大	150/149	92/94	49/48	9/7	233/236	67/62	CAD
[13]	2009	奥地利	2 565/728	1 797/483	706/217	59/26	4 300/1 183	824/269	CAD
[14]	2010	中国	139/90	129/81	10/9	0/0	268/171	10/9	CAD
[15]	2012	印度	152/300	126/191	24/99	2/10	276/481	28/119	CAD
[15]	2012	印度	156/300	124/191	28/99	4/10	276/481	36/119	CAD
[16]	2012	印度	230/300	190/191	36/99	4/10	416/481	44/119	AMI
[17]	2013	意大利	25/22	21/14	4/7	0/1	46/35	4/9	AMI
[17]	2013	意大利	16/22	9/14	7/7	0/1	25/35	7/9	AMI

参考文献	发表年份	国家	样本量（病例/对照）	基因型（病例/对照）			等位基因（病例/对照）		疾病
参考文献	发表年份	国家	样本量（病例/对照）	TT	TM	MM	T	M	疾病
[11]	2001	法国	151/249	123/179	25/65	3/5	271/423	31/75	CAD
[11]	2005	奥地利	720/432	514/319	189/100	17/13	1 217/738	223/126	CAD
[11]	2007	希腊	210/165	159/109	48/53	3/3	366/271	54/59	CAD
[12]	2007	美国	806/655	565/447	223/195	18/13	1 148/1 089	259/221	ACS
[11]	2008	中国	108/80	88/59	18/20	2/1	194/138	22/22	CAD
[11]	2008	加拿大	149/149	97/94	49/48	3/7	243/236	55/62	CAD
[11]	2008	加拿大	150/149	92/94	49/48	9/7	233/236	67/62	CAD
[13]	2009	奥地利	2 565/728	1 797/483	706/217	59/26	4 300/1 183	824/269	CAD
[14]	2010	中国	139/90	129/81	10/9	0/0	268/171	10/9	CAD
[15]	2012	印度	152/300	126/191	24/99	2/10	276/481	28/119	CAD
[15]	2012	印度	156/300	124/191	28/99	4/10	276/481	36/119	CAD
[16]	2012	印度	230/300	190/191	36/99	4/10	416/481	44/119	AMI
[17]	2013	意大利	25/22	21/14	4/7	0/1	46/35	4/9	AMI
[17]	2013	意大利	16/22	9/14	7/7	0/1	25/35	7/9	AMI

[1]	唐晴琴, 乔龙威, 尹晶平, 张胜, 丰斌, 梁玉婷. 肾病综合征患者外周血单核细胞计数与血清抗磷脂酶A2受体抗体水平的相关性[J]. 检验医学, 2023, 38(7): 647-652.
[2]	马建国, 李洪春. 冠心病患者血脂水平与心功能指标的相关性[J]. 检验医学, 2023, 38(7): 659-664.
[3]	乌有弘, 宋云霄, 朱勇, 葛雯, 卞晓波, 袁文华, 赵智赟. 血脂水平在冠心病患者冠状动脉狭窄评估和治疗中的价值[J]. 检验医学, 2023, 38(6): 584-589.
[4]	李志霞, 肖华, 卓芬, 李存盈, 李绍武, 王玉丰. 外周血LYMPH#、MO#、LMR在DLBCL患者预后评估中的价值[J]. 检验医学, 2023, 38(12): 1198-1201.
[5]	滑世轩, 代淑阳, 李冰洁, 岑东, 许泼实. 血脂正常冠心病患者炎症因子水平与病情严重程度的关系[J]. 检验医学, 2023, 38(1): 66-68.
[6]	柴凤霞, 唐丽华, 王磊. Lp-PLA2和hs-CRP在动脉粥样硬化评估中的应用[J]. 检验医学, 2022, 37(8): 798-799.
[7]	洪俊, 饶永彩. 基于CD157的四色法流式细胞术单核细胞和中性粒细胞PNH克隆检测方法的建立及评价[J]. 检验医学, 2022, 37(4): 377-381.
[8]	宋云霄, 童巍, 张海晨, 张银网, 卞晓波, 张琳琳, 袁文华, 赵智赟, 葛雯, 姚天悦. 系统性炎症指标与老年骨质疏松症患者骨折发生的相关性[J]. 检验医学, 2022, 37(3): 235-239.
[9]	李丹, 何兵, 王梦龙, 徐瑶, 万军. 传染性单核细胞增多症合并肺炎支原体感染患儿实验室检测结果分析[J]. 检验医学, 2022, 37(2): 159-161.
[10]	马建国, 朱小林, 丁永广, 尹萌, 李洪春. RDW和心肌标志物预测冠状动脉粥样硬化患者发生急性心肌梗死的价值[J]. 检验医学, 2022, 37(12): 1164-1168.
[11]	王田, 赵明, 关佳灏, 付亚文, 党小军. 西安地区健康成人NLR、PLR和LMR分布特征[J]. 检验医学, 2022, 37(11): 1023-1025.
[12]	张银网, 刘瑾瑜, 宋云霄, 葛雯, 张琳琳, 袁文华, 赵智赟. 术前SII水平与开放性骨折患者内固定术后感染的相关性[J]. 检验医学, 2022, 37(11): 1071-1074.
[13]	王晓清, 彭雪梅, 兰美锋, 潘敏. MCP-1联合CREWS在AECOPD患者不良预后评估中的价值[J]. 检验医学, 2022, 37(10): 934-938.
[14]	虞莉莎, 杨慧洁, 殷雪瑞, 葛寒宇, 王慧燕, 郑晓群. 干扰素诱导蛋白16在儿童传染性单核细胞增多症中的应用价值[J]. 检验医学, 2021, 36(9): 906-908.
[15]	刘娟, 冀旭峰, 刘玲玲, 杨春, 王伯玉. 高荧光淋巴细胞百分比对传染性单核细胞增多症的诊断价值[J]. 检验医学, 2021, 36(8): 855-856.