急性白血病医院感染病原学分析及HIF-1α、VEGF和Bcl-2表达研究
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摘要
目的探讨急性白血病医院感染病原学分析及缺氧诱导因子1α(HIF-1α)、血管内皮生长因子(VEGF)和B细胞淋巴瘤/白血病-2(Bcl-2)表达研究。方法选择舟山市普陀区人民医院和浙江省人民医院于2014年1月—2017年12月收治的急性白血病患者171例,分析医院感染发生率、病原菌分布及主要病原菌耐药情况。取患者骨髓组织病理切片,采用免疫组化染色法测定HIF-1α、VEGF和Bcl-2表达,以平均光密度值进行定量分析。结果急性白血病住院患者171例,发生医院感染患者54例(医院感染率为31. 58%);感染部位以呼吸道、口腔和胃肠道为主,分别占35. 19%、24. 07%和16. 67%;共分离病原菌71株,革兰阴性菌39株占54. 93%; 71株病原菌中,肺炎克雷伯菌15株占21. 13%、金黄色葡萄球菌12株占16. 90%、铜绿假单胞菌10株占14. 08%、凝固酶阴性葡萄球菌9株占12. 68%。分离的革兰阴性菌中,肺炎克雷伯菌对头孢哌酮耐药率较高,耐药率为53. 33%;铜绿假单胞菌对哌拉西林耐药率较高,耐药率为60. 00%。分离的革兰阳性菌中,金黄色葡萄球菌对红霉素耐药率较高,耐药率为75. 00%;凝固酶阴性葡萄球菌对红霉素耐药率较高,耐药率为66. 67%。感染组骨髓组织中HIF-1α和VEGF平均光密度值高于未感染组而Bcl-2平均光密度值低于未感染组,且差异有统计学意义(均P <0. 05)。结论急性白血病住院患者医院感染率较高,病原菌以革兰阴性菌为主,且感染患者骨髓组织中HIF-1α和VEGF呈高表达而Bcl-2呈低表达,具有重要研究意义。
Objective To investigate the etiological characteristics of nosocomial infection in patients with acute leukemia and the expression of hypoxia inducible factor 1α( HIF-1α),vascular endothelial growth factor( VEGF) and B cell lymphoma/leukemia-2( Bcl-2) in the bone marrow tissues of acute leukemia patients. Methods Total 171 cases of acute leukemia treated in our hospital between January 2014 and December 2017 were selected,and the incidence of nosocomial infection,the distribution of pathogenic bacteria and the drug resistance of the main pathogens were analyzed. The pathological sections of the bone marrow were taken for immunohistochemical staining to detect the expressions of HIF-1α,VEGF and Bcl-2,and the mean optical density was used for quantitative analysis. Results Among the 171 patients,54 cases had nosocomial infection,with a rate of 31. 58%. Of the 54 nosocomial infections,respiratory tract,oral cavity and gastrointestinal tract were the main type of infections,accounting for 35. 19%,24. 07% and 16. 67%,respectively; There were 71 strains of pathogenic bacteria isolated from 54 patients with nosocomial infection,including 39 strains of Gram-negative bacteria( 54. 93%),15 strains of Klebsiella pneumoniae( 21. 13%),12 strains of Staphylococcus aureus( 16. 90%),10 strains of Pseudomonas aeruginosa( 14. 08%) and 9 strains of coagulase-negative Staphylococcus( 12. 68%). Among the main gram-negative bacteria,Klebsiella pneumoniae had a high resistance rate to cefoperazone( 53. 33%) and Pseudomonas aeruginosa had a high resistance rate to piperacillin( 60. 00%). Among the Gram-positive bacteria,Staphylococcus aureus had a high resistance rate to erythromycin( 75. 00%) and coagulase-negative Staphylococcus had a high resistance rate to erythromycin( 66. 67%). The average optical density of HIF-1α and VEGF in bone marrow tissue of the infected group was higher than that of the uninfected group,while the average optical density of Bcl-2 was lower than that of the uninfected group( all P < 0. 05). Conclusion The incidence of nosocomial infection in patients with acute leukemia is high.The pathogenic bacteria are mainly Gram-negative bacteria,and HIF-1α,VEGF and Bcl-2 are highly expressed in the bone marrow tissues of the infected patients,which is of great significance.
Objective To investigate the etiological characteristics of nosocomial infection in patients with acute leukemia and the expression of hypoxia inducible factor 1α( HIF-1α),vascular endothelial growth factor( VEGF) and B cell lymphoma/leukemia-2( Bcl-2) in the bone marrow tissues of acute leukemia patients. Methods Total 171 cases of acute leukemia treated in our hospital between January 2014 and December 2017 were selected,and the incidence of nosocomial infection,the distribution of pathogenic bacteria and the drug resistance of the main pathogens were analyzed. The pathological sections of the bone marrow were taken for immunohistochemical staining to detect the expressions of HIF-1α,VEGF and Bcl-2,and the mean optical density was used for quantitative analysis. Results Among the 171 patients,54 cases had nosocomial infection,with a rate of 31. 58%. Of the 54 nosocomial infections,respiratory tract,oral cavity and gastrointestinal tract were the main type of infections,accounting for 35. 19%,24. 07% and 16. 67%,respectively; There were 71 strains of pathogenic bacteria isolated from 54 patients with nosocomial infection,including 39 strains of Gram-negative bacteria( 54. 93%),15 strains of Klebsiella pneumoniae( 21. 13%),12 strains of Staphylococcus aureus( 16. 90%),10 strains of Pseudomonas aeruginosa( 14. 08%) and 9 strains of coagulase-negative Staphylococcus( 12. 68%). Among the main gram-negative bacteria,Klebsiella pneumoniae had a high resistance rate to cefoperazone( 53. 33%) and Pseudomonas aeruginosa had a high resistance rate to piperacillin( 60. 00%). Among the Gram-positive bacteria,Staphylococcus aureus had a high resistance rate to erythromycin( 75. 00%) and coagulase-negative Staphylococcus had a high resistance rate to erythromycin( 66. 67%). The average optical density of HIF-1α and VEGF in bone marrow tissue of the infected group was higher than that of the uninfected group,while the average optical density of Bcl-2 was lower than that of the uninfected group( all P < 0. 05). Conclusion The incidence of nosocomial infection in patients with acute leukemia is high.The pathogenic bacteria are mainly Gram-negative bacteria,and HIF-1α,VEGF and Bcl-2 are highly expressed in the bone marrow tissues of the infected patients,which is of great significance.
引文
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[12]徐娜,李娜,于昊,等.急性白血病患者院内感染危险因素的调查研究[J].中国卫生产业,2016,13(32):163-165.
[13] SAKELLARI I,GAVRILAKI E,CHATZIIOANNOU K,et al. Longterm outcomes of total body irradiation plus cyclophosphamide versus busulfan plus cyclophosphamide as conditioning regimen for acute lymphoblastic leukemia:a comparative study[J]. Ann Hematol,2018,97(10):1987-1994.
[14] VAN DER PLAS E,ERDMAN L,NIEMAN B J,et al. Characterizing neurocognitive late effects in childhood leukemia survivors using a combination of neuropsychological and cognitive neuroscience measures[J]. Child Neuropsychol,2018,24(8):999-1014.
[15]张艳,周萍,高翠霞.急性白血病医院感染的危险因素及护理对策[J].实用临床护理学电子杂志,2018,3(11):33.
[16] JIANG J,YIN X Y,SONG X W,et al. EgoNet identifies differential ego-modules and pathways related to prednisolone resistance in childhood acute lymphoblastic leukemia[J]. Hematology,2018,23(4):221-227.
[17]刘芸宏,王书会,王静娜,等.不同分型急性白血病患者医院感染直接经济损失研究[J].中国感染控制杂志,2016,15(12):942-944.
[18]云清英,徐刚. HIF-1α在成人急性淋巴细胞白血病患者骨髓单个核细胞中的表达及意义[J].中国现代医学杂志,2017,9(21):49-53.
[19]刘婉文,廖友明,万忠和,等.血管内皮生长因子及其受体Flt、KDR的表达水平与儿童急性白血病的关系研究[J].中华医院感染学杂志,2016,26(14):3313-3315.
[20]陈泽,蔡志梅,赵利东,等. BCL-2与PD-L1联合检测在预测初治急性白血病预后中的价值分析[J].中国实验血液学杂志,2017,17(6):1636-1640.
[2] CASSADAY R D,STEVENSON P A,WOOD B L,et al. Description and prognostic significance of the kinetics of minimal residual disease status in adults with acute lymphoblastic leukemia treated with HyperCVAD[J]. Am J Hematol,2018,93(4):546-552.
[3] PASHAIEFAR H,YAGHMAIE M,TAVAKKOLY-BAZZAZ J,et al.The association between PARP1 and LIG3 expression levels and chromosomal translocations in acute myeloid leukemia patients[J]. Cell J,2018,20(2):204-210.
[4]李艳红,魏朝辉.急性白血病医院感染的危险因素及护理对策[J].山西医药杂志,2017,46(19):2398-2400.
[5]代利霞,涂小琼,蔡冰冰. VEGF对急性白血病预后的预测作用分析[J].国际检验医学杂志,2017,38(23):3288-3290.
[6]张之南.血液病的诊断及疗效标准[M].北京:科学技术出版社,1998:168-196.
[7]中华人民共和国卫生部.医院感染诊断标准(试行)[J].中华医学杂志,2001,81(5):314-321.
[8] ALDOSS I,STEIN A S. Advances in adult acute lymphoblastic leukemia therapy[J]. Leuk Lymphoma,2018,59(5):1033-1050.
[9]董洪婧,彭庆峰,张奎,等.急性白血病患者医院感染的危险因素分析[J].中华医院感染学杂志,2016,26(16):3724-3726.
[10] CAO H,XIE J,GUO L,et al. All-trans retinoic acid induces autophagic degradation of ubiquitin-like modifier activating enzyme 3 in acute promyelocytic leukemia cells[J]. Leuk Lymphoma,2018,59(5):1222-1230.
[11]周竞奋,陈琰,朱振峰,等.急性白血病患者医院感染的临床特点分析[J].中华医院感染学杂志,2018,28(7):987-990.
[12]徐娜,李娜,于昊,等.急性白血病患者院内感染危险因素的调查研究[J].中国卫生产业,2016,13(32):163-165.
[13] SAKELLARI I,GAVRILAKI E,CHATZIIOANNOU K,et al. Longterm outcomes of total body irradiation plus cyclophosphamide versus busulfan plus cyclophosphamide as conditioning regimen for acute lymphoblastic leukemia:a comparative study[J]. Ann Hematol,2018,97(10):1987-1994.
[14] VAN DER PLAS E,ERDMAN L,NIEMAN B J,et al. Characterizing neurocognitive late effects in childhood leukemia survivors using a combination of neuropsychological and cognitive neuroscience measures[J]. Child Neuropsychol,2018,24(8):999-1014.
[15]张艳,周萍,高翠霞.急性白血病医院感染的危险因素及护理对策[J].实用临床护理学电子杂志,2018,3(11):33.
[16] JIANG J,YIN X Y,SONG X W,et al. EgoNet identifies differential ego-modules and pathways related to prednisolone resistance in childhood acute lymphoblastic leukemia[J]. Hematology,2018,23(4):221-227.
[17]刘芸宏,王书会,王静娜,等.不同分型急性白血病患者医院感染直接经济损失研究[J].中国感染控制杂志,2016,15(12):942-944.
[18]云清英,徐刚. HIF-1α在成人急性淋巴细胞白血病患者骨髓单个核细胞中的表达及意义[J].中国现代医学杂志,2017,9(21):49-53.
[19]刘婉文,廖友明,万忠和,等.血管内皮生长因子及其受体Flt、KDR的表达水平与儿童急性白血病的关系研究[J].中华医院感染学杂志,2016,26(14):3313-3315.
[20]陈泽,蔡志梅,赵利东,等. BCL-2与PD-L1联合检测在预测初治急性白血病预后中的价值分析[J].中国实验血液学杂志,2017,17(6):1636-1640.