临床分离的耐碳青霉烯类肠杆菌科细菌的研究进展_West China Medical Journal

Authors：

刘雅 ,  康梅

Corresponding author：

康梅, Email: liuya20131130@163.com

Keywords：

肠杆菌科细菌; 碳青霉烯类抗生素; 耐药

DOI：

10.7507/1002-0179.20130199

Video：

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肠杆菌科细菌是医院感染的重要病原菌，分离率高。碳青霉烯类抗生素对绝大多数β-内酰胺酶稳定，抗菌谱广，抗菌活性强。然而随着碳青霉烯类抗生素的大量使用，全球许多地区出现了碳青霉烯类耐药的肠杆菌科细菌报道，本文就其流行病学现状、耐药机制及检测方法作一综述。

Citation： 刘雅,康梅. 临床分离的耐碳青霉烯类肠杆菌科细菌的研究进展. West China Medical Journal, 2013, 28(4): 631-636. doi: 10.7507/1002-0179.20130199 Copy

1.	洪秀华, 刘运德, 李向阳, 等. 临床微生物学检验[M]. 北京: 中国医药科技出版社, 2010: 304-306.
2.	Birgy A, Bidet P, Genel N, et al. Phenotypic screening of carbapenemases and associated β-lactamases in carbapenem-resistant enterobacteriacease[J]. J Olin Microbiol, 2012, 59(4): 1295-1302.
3.	Naas T, Vandel L, Sougakoff W, et al. Cloning and sequence analysis of the gene for a carbapenem-hydrolyzing class A beta-lactamase, Sme-1, from Serratia marcescens S6[J]. Antimicrob Agents Chemother, 1994, 38(6): 1262-1270.
4.	Queenan AM, Torres-Viera C, Howard S. Gold, et al. SME-type carbapenem-hydrolyzing class A beta-lactamases from geographically diverse Serratia marcescens strains[J]. Antimicrob Agents Chemother, 2000, 44(11): 3035-3039.
5.	Yang Y, Wu P, Livermore D. Biochemical characterization of a beta-lactamase that hydrolyzes penems and carbapenems from two Serratia marcescens isolates[J]. Antimicrob Agents Chemotherapy, 1990, 34: 755-758.
6.	Borgia S, Lastovetska O, Richardson D, et al. Outbreak of carbapenem-resistant enterobacteriaceae containing blaNDM-1, Ontario, Canada[J]. Clin Infect Dis, 2012, 55(11): 109-117.
7.	Adlera A, Carmelia BY. Dissemination of the Klebsiella pneumonia carbapenemase in the health care settings: tracking the trails of an elusive offender[J]. mBio, 2011, 2(6): 280-291.
8.	Curcio DJ. Antibiotic prescription in intensive care units in Latin America[J]. Revista Argentina de Microbiología, 2011, 43: 203-211.
9.	Pfeifer Y, Schlatterer K, Engelmann E, et al. Emergence of OXA-48-type carbapenemase-producing Enterobacteriaceae in German hospitals[J]. Antimicrob Agents Chemother, 2012, 56(4): 2125-2128.
10.	Agodi A, Voulgari E, Barchitta M, et al. Containment of an outbreak of KPC-3-producing klebsiella pneumoniae in Italy[J]. J Clin Microbiol, 2011, 49(11): 3986-3989.
11.	Leverstein-van Hall MA, Stuart JC, Voets GM, et al. Carbapenem-resistant Klebsiella pneumoniae following foreign travel[J]. Ned Tijdschr Geneeskd, 2010, 154(37): 1736.
12.	Us E, Tekeli A, Arikan AO, et al. Molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae strains isolated between 2004-2007 in Ankara University hospital, Turkey[J]. Mikrobiyol Bul, 2010, 44(1): 1-10.
13.	Shen P, Wei ZQ, Jiang Y, et al. Novel genetic environment of the carbapenem-hydrolyzing β-lactamase KPC-2 among enterobacteriaceae in China[J]，Antimicrob Agents Chemotherapy, 2009 , 53(10): 4333-4338.
14.	Roh KH, Lee CK, Sohn JW, et al. Isolation of a Klebsiella pneumoniae isolate of sequence type 258 producing KPC-2 carbapenemase in Korea[J]. Korean J Lab Med, 2011, 31(4): 298-301.
15.	Saidani M, Hammami S, Kammoun A, et al. Emergence of carbapenem resistant Enterobacteriaceae producing OXA-48 carbapenemase in Tunisia[J]. J Med Microbiol, 2012, 61(12): 1746-1749.
16.	Datta P, Gupta V, Garg S, et al. Phenotypic method for differentiation of carbapenemases in enterobacteriaceae: study from north India[J]. Indian J Pathol Microbiol, 2012, 55(3): 357-360.
17.	Arpin C, Noury P, Boraud D, et al. NDM-1-producing Klebsiella pneumoniae resistant to colistin in a French community patient without history of foreign travel[J]. Antimicrob Agents Chemother, 2012, 56(6): 3432-3434.
18.	Gaynes RP, Culver DH. Resistance to imipenem among selected gram-negative bacilli in the United States[J]. Infect Control Hosp Epidemiol, 1992, 13(1): 10-14.
19.	Rhomberg PR, Jones RN, et al. Summary trends for the meropenem yearly susceptibility test information collection program: a 10-year experience in the United States(1999-2008)[J]. Diagn Microbiol Infect Dis , 2009, 65(4): 414-426.
20.	Hidron AI, Edwards JR, Patel J, et al. NHSN annualupdate: antimicrobial-resistant pathogens associated with ealthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention[J]. Infect Con Hosp Epidemio, 2008, 29(11): 996-1011.
21.	肖永红, 王进, 赵彩云, 等. 2006-2007年Mohnarin细菌耐药监测[J]. 中华医院感染学杂志, 2008, 18(8): 1051-1056.
22.	李丽, 田磊, 陈中举, 等. 卫生部全国细菌耐药监测网2010年中南地区细菌耐药性监测[J]. 中国临床药理学杂志, 2011, 27(12): 940-947.
23.	徐修礼, 周珊.卫生部全国细菌耐药监测网2010年西北地区细菌耐药性监测[J]. 中国临床药理学杂志, 2011, 27(12): 925-931.
24.	张智洁, 王军. 卫生部全国细菌耐药监测网2010年东北地区细菌耐药性监测[J]. 中国临床药理学杂志, 2011, 27(12): 948-975.
25.	马序竹, 郑波.卫生部全国细菌耐药监测网2010年北京地区细菌耐药性监测[J]. 中国临床药理学杂志, 2011, 27(12): 919-924.
26.	肖书念, 卓超, 钟南山. 卫生部全国细菌耐药监测网2010年广东地区细菌耐药性监测[J].中国临床药理学杂志, 2011, 27(12): 965-971.
27.	张纬博, 孙景勇, 倪语星. 卫生部全国细菌耐药监测网2010年华东地区细菌耐药性监测[J].中国临床药理学杂志, 2011, 27(12): 959-964.
28.	杨央, 吕火祥, 胡庆丰, 等. 1456株连续分离的肺炎克雷伯菌临床分布及耐药性分析[J].中国卫生检验杂志, 2010, 20(9): 2232-2234.
29.	蔡佳昌. 肠杆菌科细菌对碳青霉烯类抗生素耐药机制研究[D]. 浙江：浙江大学博士学位论文. 2010.
30.	Yigit H, Queenan AM, Anderson GJ, et al. Novel carbapenem-hydrolyzing β-Lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae[J]. Antimicrob Agents Chemotherapy, 2001, 45(4): 1151-1161.
31.	Miriagou V, Tzouvelekis LS, Rossiter S, et al. Imipenem resistance in a salmonella clinical strain due to plasmid-mediated class a carbapenemase KPC-2[J]. Antimicrob Agents Chemotherapy, 2003, 47(4): 1297-300.
32.	Bratu S, Landman D, Alam M, et al. Detection of KPC carbapenem-hydrolyzing enzymes in enterobacterspp. from Brooklyn, New York[J]. Antimicrob Agents Chemother , 2004, 48(12): 4793-4799.
33.	Woodford N, Tierno PM, Young JrK, et al. Outbreak of klebsiella pneumoniae producing a new carbapenem-hydrolyzing Class A-Lactamase, KPC-3, in a New York Medical Center[J]. Antimicrob Agents Chemother, 2005, 49(2): 776-778.
34.	Landman D, Babu E, Patel JB, et al. Transmission of carbapenem-resistant pathogens in New York City hospitals: progress and frustrationm[J]. Antimicrob Chemother, 2012, 67(6): 1427-1431.
35.	Landman D, Bratu S, Kochar S, et al. Evolution of antimicrobial resistance among Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae in Brooklyn, NY[J]. J Antimicro Chemother, 2007, 60(1): 78-82.
36.	Gupta N, Limbago BM, Patel JB, et al. Carbapenem-resistant enterobacteriaceae: epidemiology and prevention[J]. Clin Infect Dis, 2011, 53(1): 60-67.
37.	Mathers AJ, Cox HL, Kitchel B, et al. Molecular dissection of an outbreak of carbapenem-resistant enterobacteriaceae reveals intergenus kpc carbapenemase transmission through a promiscuous plasmid[J]. mBio, 2011, 2(6): 204-211 .
38.	Osano E, Arakawa Y, Wacharotayankun R, et al. Molecular characterization of an enterobacterial metallo beta-lactamase found in a clinical isolate of Serratia marcescens that shows imipenem resistance[J]. Antimicrob Agents Chemother, 1994, 38(1): 71-78.
39.	Miriagou V, Tzelepi E, Gianneli D, et al. Escherichia coli with a self-transferable, multiresistant plasmid coding for metallo-β-Lactamase VIM-1[J]. Antimicrob Agents Chemother, 2003, 47(1): 395-397.
40.	Yong D, Toleman MA, Giske CG, et al. Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India[J]. Antimicrob Agents Chemother, 2009 , 53(12): 5046-54.
41.	Deshpande LM, Mendes RE, Castanheira M, et al. Dissemination of NDM-1-producing enterobacteriaceae in India [abstract C2-701]. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy[M]. Boston: American Society for Microbiology, 2010.
42.	Poirel L, Héritier C, Tolün V, et al. Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella pneumoniae[J]. Antimicrob Agents Chemother J, 2004, 48(1) : 15-22 .
43.	Cre´ met L, Bourigault CL, Lepelletier D, et al. Nosocomial outbreak of carbapenem-resistant Enterobacter cloacae highlighting the interspecies transferability of the blaOXA-48 gene in the gut flora [J]. Antimicrob Chemother, 2012, 67 (4): 1041-1043.
44.	李俐, 蒋燕群.大肠埃希菌和肺炎克雷伯菌外膜蛋白与耐药机制的研究进展[J]. 上海交通大学学报·医学版, 2010, 30(11): 1433-1436.
45.	Sureda LG, Dome´nech-Sa´nchez A, Barbier M, et al. OmpK26, a novel porin associated with carbapenem resistance in Klebsiella pneumoniae[J]. Antimicrob Agents Chemother, 2011, 55(10) : 4742-4747.
46.	Neuwirth C, Siébor E, Duez JM, et al. Imipenem resistance in clinical isolates of Proteus mirabilis associated with alterations in penicillin-binding proteins[J]. Antimicrob Agents Chemother, 1995, 36 (2): 335-342.
47.	Lee K, Lim YS, Yong D, et al. Evaluation of the Hodge test and the imipenem-EDTA double disk synergy test for differentiating metallo-β- lactamase-producing isolates of Pseudomonas spp and Acinetobacter spp[J]. J Clin Microbiol, 2003, 41(10): 4623-4629.
48.	McGettigan SE, Andreacchio K, Edelstein PH. Specificity of ertapenem susceptibility screening for detection of Klebsiella pneumoniae carbapenemases[J]. J Clin Microbiol, 2009, 47(3): 785-786.
49.	Anderson KF, Lonsway DR, Rasheed JK, et al. Evaluation of methods to identify the Klebsiella pneumoniae carbapenemase in enterobacteriaceae[J]. J Clin Microbiol, 2007, 45(8): 2723-2725.
50.	Hindiyeh M, Smollan G, Grossman Z, et al. Rapid detection of blaKPC carbapenemase genes by internally controlled real-time pcr assay using[J]. J Clin Microbiol, 2011, 49(7) : 2480-2484 .

1. 　洪秀华, 刘运德, 李向阳, 等. 临床微生物学检验[M]. 北京: 中国医药科技出版社, 2010: 304-306.
2. 　Birgy A, Bidet P, Genel N, et al. Phenotypic screening of carbapenemases and associated β-lactamases in carbapenem-resistant enterobacteriacease[J]. J Olin Microbiol, 2012, 59(4): 1295-1302.
3. 　Naas T, Vandel L, Sougakoff W, et al. Cloning and sequence analysis of the gene for a carbapenem-hydrolyzing class A beta-lactamase, Sme-1, from Serratia marcescens S6[J]. Antimicrob Agents Chemother, 1994, 38(6): 1262-1270.
4. 　Queenan AM, Torres-Viera C, Howard S. Gold, et al. SME-type carbapenem-hydrolyzing class A beta-lactamases from geographically diverse Serratia marcescens strains[J]. Antimicrob Agents Chemother, 2000, 44(11): 3035-3039.
5. 　Yang Y, Wu P, Livermore D. Biochemical characterization of a beta-lactamase that hydrolyzes penems and carbapenems from two Serratia marcescens isolates[J]. Antimicrob Agents Chemotherapy, 1990, 34: 755-758.
6. 　Borgia S, Lastovetska O, Richardson D, et al. Outbreak of carbapenem-resistant enterobacteriaceae containing blaNDM-1, Ontario, Canada[J]. Clin Infect Dis, 2012, 55(11): 109-117.
7. 　Adlera A, Carmelia BY. Dissemination of the Klebsiella pneumonia carbapenemase in the health care settings: tracking the trails of an elusive offender[J]. mBio, 2011, 2(6): 280-291.
8. 　Curcio DJ. Antibiotic prescription in intensive care units in Latin America[J]. Revista Argentina de Microbiología, 2011, 43: 203-211.
9. 　Pfeifer Y, Schlatterer K, Engelmann E, et al. Emergence of OXA-48-type carbapenemase-producing Enterobacteriaceae in German hospitals[J]. Antimicrob Agents Chemother, 2012, 56(4): 2125-2128.
10. 　Agodi A, Voulgari E, Barchitta M, et al. Containment of an outbreak of KPC-3-producing klebsiella pneumoniae in Italy[J]. J Clin Microbiol, 2011, 49(11): 3986-3989.
11. 　Leverstein-van Hall MA, Stuart JC, Voets GM, et al. Carbapenem-resistant Klebsiella pneumoniae following foreign travel[J]. Ned Tijdschr Geneeskd, 2010, 154(37): 1736.
12. 　Us E, Tekeli A, Arikan AO, et al. Molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae strains isolated between 2004-2007 in Ankara University hospital, Turkey[J]. Mikrobiyol Bul, 2010, 44(1): 1-10.
13. 　Shen P, Wei ZQ, Jiang Y, et al. Novel genetic environment of the carbapenem-hydrolyzing β-lactamase KPC-2 among enterobacteriaceae in China[J]，Antimicrob Agents Chemotherapy, 2009 , 53(10): 4333-4338.
14. 　Roh KH, Lee CK, Sohn JW, et al. Isolation of a Klebsiella pneumoniae isolate of sequence type 258 producing KPC-2 carbapenemase in Korea[J]. Korean J Lab Med, 2011, 31(4): 298-301.
15. 　Saidani M, Hammami S, Kammoun A, et al. Emergence of carbapenem resistant Enterobacteriaceae producing OXA-48 carbapenemase in Tunisia[J]. J Med Microbiol, 2012, 61(12): 1746-1749.
16. 　Datta P, Gupta V, Garg S, et al. Phenotypic method for differentiation of carbapenemases in enterobacteriaceae: study from north India[J]. Indian J Pathol Microbiol, 2012, 55(3): 357-360.
17. 　Arpin C, Noury P, Boraud D, et al. NDM-1-producing Klebsiella pneumoniae resistant to colistin in a French community patient without history of foreign travel[J]. Antimicrob Agents Chemother, 2012, 56(6): 3432-3434.
18. 　Gaynes RP, Culver DH. Resistance to imipenem among selected gram-negative bacilli in the United States[J]. Infect Control Hosp Epidemiol, 1992, 13(1): 10-14.
19. 　Rhomberg PR, Jones RN, et al. Summary trends for the meropenem yearly susceptibility test information collection program: a 10-year experience in the United States(1999-2008)[J]. Diagn Microbiol Infect Dis , 2009, 65(4): 414-426.
20. 　Hidron AI, Edwards JR, Patel J, et al. NHSN annualupdate: antimicrobial-resistant pathogens associated with ealthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention[J]. Infect Con Hosp Epidemio, 2008, 29(11): 996-1011.
21. 　肖永红, 王进, 赵彩云, 等. 2006-2007年Mohnarin细菌耐药监测[J]. 中华医院感染学杂志, 2008, 18(8): 1051-1056.
22. 　李丽, 田磊, 陈中举, 等. 卫生部全国细菌耐药监测网2010年中南地区细菌耐药性监测[J]. 中国临床药理学杂志, 2011, 27(12): 940-947.
23. 　徐修礼, 周珊.卫生部全国细菌耐药监测网2010年西北地区细菌耐药性监测[J]. 中国临床药理学杂志, 2011, 27(12): 925-931.
24. 　张智洁, 王军. 卫生部全国细菌耐药监测网2010年东北地区细菌耐药性监测[J]. 中国临床药理学杂志, 2011, 27(12): 948-975.
25. 　马序竹, 郑波.卫生部全国细菌耐药监测网2010年北京地区细菌耐药性监测[J]. 中国临床药理学杂志, 2011, 27(12): 919-924.
26. 　肖书念, 卓超, 钟南山. 卫生部全国细菌耐药监测网2010年广东地区细菌耐药性监测[J].中国临床药理学杂志, 2011, 27(12): 965-971.
27. 　张纬博, 孙景勇, 倪语星. 卫生部全国细菌耐药监测网2010年华东地区细菌耐药性监测[J].中国临床药理学杂志, 2011, 27(12): 959-964.
28. 　杨央, 吕火祥, 胡庆丰, 等. 1456株连续分离的肺炎克雷伯菌临床分布及耐药性分析[J].中国卫生检验杂志, 2010, 20(9): 2232-2234.
29. 　蔡佳昌. 肠杆菌科细菌对碳青霉烯类抗生素耐药机制研究[D]. 浙江：浙江大学博士学位论文. 2010.
30. 　Yigit H, Queenan AM, Anderson GJ, et al. Novel carbapenem-hydrolyzing β-Lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae[J]. Antimicrob Agents Chemotherapy, 2001, 45(4): 1151-1161.
31. 　Miriagou V, Tzouvelekis LS, Rossiter S, et al. Imipenem resistance in a salmonella clinical strain due to plasmid-mediated class a carbapenemase KPC-2[J]. Antimicrob Agents Chemotherapy, 2003, 47(4): 1297-300.
32. 　Bratu S, Landman D, Alam M, et al. Detection of KPC carbapenem-hydrolyzing enzymes in enterobacterspp. from Brooklyn, New York[J]. Antimicrob Agents Chemother , 2004, 48(12): 4793-4799.
33. 　Woodford N, Tierno PM, Young JrK, et al. Outbreak of klebsiella pneumoniae producing a new carbapenem-hydrolyzing Class A-Lactamase, KPC-3, in a New York Medical Center[J]. Antimicrob Agents Chemother, 2005, 49(2): 776-778.
34. 　Landman D, Babu E, Patel JB, et al. Transmission of carbapenem-resistant pathogens in New York City hospitals: progress and frustrationm[J]. Antimicrob Chemother, 2012, 67(6): 1427-1431.
35. 　Landman D, Bratu S, Kochar S, et al. Evolution of antimicrobial resistance among Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae in Brooklyn, NY[J]. J Antimicro Chemother, 2007, 60(1): 78-82.
36. 　Gupta N, Limbago BM, Patel JB, et al. Carbapenem-resistant enterobacteriaceae: epidemiology and prevention[J]. Clin Infect Dis, 2011, 53(1): 60-67.
37. 　Mathers AJ, Cox HL, Kitchel B, et al. Molecular dissection of an outbreak of carbapenem-resistant enterobacteriaceae reveals intergenus kpc carbapenemase transmission through a promiscuous plasmid[J]. mBio, 2011, 2(6): 204-211 .
38. 　Osano E, Arakawa Y, Wacharotayankun R, et al. Molecular characterization of an enterobacterial metallo beta-lactamase found in a clinical isolate of Serratia marcescens that shows imipenem resistance[J]. Antimicrob Agents Chemother, 1994, 38(1): 71-78.
39. 　Miriagou V, Tzelepi E, Gianneli D, et al. Escherichia coli with a self-transferable, multiresistant plasmid coding for metallo-β-Lactamase VIM-1[J]. Antimicrob Agents Chemother, 2003, 47(1): 395-397.
40. 　Yong D, Toleman MA, Giske CG, et al. Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India[J]. Antimicrob Agents Chemother, 2009 , 53(12): 5046-54.
41. 　Deshpande LM, Mendes RE, Castanheira M, et al. Dissemination of NDM-1-producing enterobacteriaceae in India [abstract C2-701]. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy[M]. Boston: American Society for Microbiology, 2010.
42. 　Poirel L, Héritier C, Tolün V, et al. Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella pneumoniae[J]. Antimicrob Agents Chemother J, 2004, 48(1) : 15-22 .
43. 　Cre´ met L, Bourigault CL, Lepelletier D, et al. Nosocomial outbreak of carbapenem-resistant Enterobacter cloacae highlighting the interspecies transferability of the blaOXA-48 gene in the gut flora [J]. Antimicrob Chemother, 2012, 67 (4): 1041-1043.
44. 　李俐, 蒋燕群.大肠埃希菌和肺炎克雷伯菌外膜蛋白与耐药机制的研究进展[J]. 上海交通大学学报·医学版, 2010, 30(11): 1433-1436.
45. 　Sureda LG, Dome´nech-Sa´nchez A, Barbier M, et al. OmpK26, a novel porin associated with carbapenem resistance in Klebsiella pneumoniae[J]. Antimicrob Agents Chemother, 2011, 55(10) : 4742-4747.
46. 　Neuwirth C, Siébor E, Duez JM, et al. Imipenem resistance in clinical isolates of Proteus mirabilis associated with alterations in penicillin-binding proteins[J]. Antimicrob Agents Chemother, 1995, 36 (2): 335-342.
47. 　Lee K, Lim YS, Yong D, et al. Evaluation of the Hodge test and the imipenem-EDTA double disk synergy test for differentiating metallo-β- lactamase-producing isolates of Pseudomonas spp and Acinetobacter spp[J]. J Clin Microbiol, 2003, 41(10): 4623-4629.
48. 　McGettigan SE, Andreacchio K, Edelstein PH. Specificity of ertapenem susceptibility screening for detection of Klebsiella pneumoniae carbapenemases[J]. J Clin Microbiol, 2009, 47(3): 785-786.
49. 　Anderson KF, Lonsway DR, Rasheed JK, et al. Evaluation of methods to identify the Klebsiella pneumoniae carbapenemase in enterobacteriaceae[J]. J Clin Microbiol, 2007, 45(8): 2723-2725.
50. 　Hindiyeh M, Smollan G, Grossman Z, et al. Rapid detection of blaKPC carbapenemase genes by internally controlled real-time pcr assay using[J]. J Clin Microbiol, 2011, 49(7) : 2480-2484 .

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