中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

Change in follicular helper T cells in the peripheral blood and spleen of rats after Echinococcus multilocularis infection

DOI: 10.3969/j.issn.1001-5256.2021.07.035
Research funding:

Qinghai University Affiliated Hospital for Young and Middle-aged Project (ASRF-2018-YB-01);

Qinghai Provincial Department of Science and Technology Major Science and Technology Project (2016-SF-A5);

National Natural Science Foundation of China (81960129)

  • Received Date: 2020-12-10
  • Accepted Date: 2021-01-12
  • Published Date: 2021-07-20
  •   Objective  To investigate the level of follicular helper T (Tfh) cells in the peripheral blood and spleen of the host after Echinococcus multilocularis infection and its association with the progression of echinococcosis.  Methods  A total of 20 Sprague-Dawley rats were randomly divided into normal control group and model group, with 10 rats in each group. The rats in the model group were inoculated with about 2000 protoscoleces in the right liver under direct-view laparotomy, and those in the control group were not given any treatment. The rats were anesthetized and sacrificed after 3 months to collect peripheral blood and spleen cells, and with CD4+CXCR5+PD1+ as the marker of Tfh cells, flow cytometry was used to measure the level of Tfh cells in peripheral blood and spleen. The t-test was used for comparison of Tfh cells between the two groups.  Results  After 3 months of Echinococcus multilocularis infection, marked lesions were observed in the liver, and HE staining showed the presence of protoscoleces in the lesions. The proportion of CD4+CXCR5+PD1+Tfh cells in CD4+ cells in peripheral blood was 25.63%±3.47% in the model group and 11.12%±2.94% in the normal control group (t=10.230, P < 0.001), a nd the model group had a significantly lower proportion of CD4+CXCR5+PD1+Tfh cells in all cells than the normal control group (0.08%±0.02% vs 0.18%±0.05%, t=5.520, P < 0.001). For the model group, the proportion of CD4+CXCR5+PD1+Tfh cells in all cells in the spleen decreased to 3.00%±0.42%, which was significantly lower than the proportion of 5.30%±1.40% in the normal control group (t=4.769, P < 0.001).  Conclusion  Tfh cells in peripheral blood are closely associated with the progression of echinococcosis and are expected to become an indicator of Echinococcus multilocularis infection.

     

  • 全世界约有一半新诊断的肝细胞癌(hepatocellular cell carcinoma,HCC)病例发生在我国,其中HBV感染是主要危险因素,占全球HCC病例的50%~80%[1]。HBV通过多种机制在宿主细胞中持续存在,从而导致慢性HBV感染[2],并且诱导HCC发生[3]。超过80%的HCC在肝硬化基础上发展,这表明肝硬化在肝癌前环境中起着重要作用[4]。因此慢性HBV感染和肝硬化是肝癌发生的高风险因素。由于缺乏明显的症状和有效的筛查策略,80%的HCC患者被诊断时已为中晚期,其中仅有30%~40%患者符合当前有效治疗方案的条件[5],故在早期将慢性HBV感染、肝硬化与HCC区分诊断是延长患者生存期甚至根治HCC的关键。现急需一种检测方式能够在患有良性肝病的肝癌高危人群中早期筛查出HCC,从而降低病死率。影像学检查作为有效筛查方法被应用于临床,但是受限于设备以及检测人员。实验室检测则更能筛查大量人群,目前主要的早期实验室筛查方法为检测患者血清AFP,但单一指标检测的敏感度与特异度存在限制。考虑联合指标检测能够提高诊断效率,本文将探究AFP与GGT/AST联合检测在良性肝病和HCC区别诊断中发挥的作用,以期为临床诊断提供新的参考依据。

    选取2019年1月15日—6月15日于本院诊治的慢性乙型肝炎患者(CHB组)、乙型肝炎肝硬化患者(LC组)、HBV相关HCC患者(HCC组),另选取同期健康体检者作为对照(HC组)。纳入标准:(1)HCC组患者HBsAg为阳性且诊断完全符合《原发性肝癌诊疗规范(2017年版)》[6]; (2)HCC组、CHB组和LC组患者均为首次诊断,在接受治疗前收集生化指标; (3)临床资料完整。排除标准:(1)排除HCC之外的恶性肿瘤; (2)排除HBV以外的其他肝炎病毒感染; (3)排除患有严重糖尿病、甲状腺亢进以及心血管疾病等患者; (4)排除妊娠患者。研究对象均自愿参与本项研究。

    采集所有研究对象空腹6~8 h后的静脉血5 ml,以转速3500 r/min(离心半径=16 cm)离心5 min,分离血清后-80 ℃冷冻备用。采用Siemens公司ADVIACENTUAR XP全自动化学发光免疫分析仪及配套试剂盒检测血清AFP水平,参考区间为0~8.0 ng/ml。使用Siemens公司ADVIA2400全自动生化分析仪检测AST、ALT、GGT水平,参考区间分别为15~40、5~40、10~60 U/L。以上操作严格依据说明书进行,所有检测均在试剂盒说明书规定时间内完成,且严格遵守试验相关操作规程。

    本研究方案经由武汉大学人民医院临床研究伦理委员会审批,批号:WDRY2018-K047。

    采用SPSS 23.0软件、GraphPad Prism 6.0和MedCalc 18.2.1对数据进行统计分析。正态分布计量资料以x±s表示,多组间比较采用方差分析,进一步两两比较采用LSD-t检验。偏态分布计量资料以M(P25~P75)表示,多组间比较采用Kruskal-Wallis H检验,进一步两两比较采用Nemenyi检验。计数资料组间比较采用χ2检验。通过二元logistic回归分析,计算出预测变量,并绘制AFP、GGT/AST以及预测变量单独或联合检测的受试者工作特征曲线(ROC曲线),计算曲线下面积(AUC)及敏感度、特异度,采用Z检验对AUC进行比较。P<0.05为差异有统计学意义。

    共纳入研究对象352例,其中HC组86例,男42例,女44例,年龄23~82岁,平均(55.90±15.19)岁; CHB组68例,男38例,女30例,年龄22~77岁,平均(51.40±10.59)岁,HBV DNA阳性50例; LC组69例,男34例,女35例,年龄28~79岁,平均(53.49±11.35)岁,HBV DNA阳性36例,Child-Pugh A级25例,B级32例,C级12例; HCC组129例,男70例,女59例,年龄24~78岁,平均(54.60±11.17)岁,HBV DNA阳性50例,Child-Pugh A级79例,B级41例,C级9例,BCLC分期A期21例,B期31例,C期77例。4组研究对象年龄(F=1.455,P=0.227)与性别分布(χ2=1.346,P=0.718)差异均无统计学意义。

    HCC组与HC组、CHB组、LC组之间患者的AFP、GGT/AST、GGT比较差异均有统计学意义(P值均<0.05)(表 1)。

    表  1  各组AFP、GGT、AST及GGT/AST血清学水平比较
    组别 例数 AFP(ng/ml) GGT/AST GGT(U/L) AST(U/L)
    HC组 86 3.35(2.20~4.70) 0.98(0.71~1.36) 20.00(15.00~27.00) 21.00(18.00~24.00)
    CHB组 68 4.35(2.35~15.75) 0.82(0.46~1.25) 51.00(23.75~140.75)1) 61.00(34.25~125.00)1)
    LC组 69 8.60(2.70~54.20)1) 0.97(0.55~1.81) 69.00(27.00~113.00)1) 47.00(31.00~88.00)1)
    HCC组 129 157.10(9.90~6126.40)1)2)3) 2.00(1.19~3.11)1)2)3) 98.00(45.00~207.00)1)2)3) 46.00(29.00~88.00)1)2)
    H 124.018 70.202 126.282 135.987
    P <0.001 <0.001 <0.001 <0.001
    注:与HC组比较,1)P<0.05;与CHB组比较,2)P<0.05;与LC组比较,3)P<0.05。
    下载: 导出CSV 
    | 显示表格

    采用二元logistic回归分析得到不同组别之间两种指标的联合回归模型,然后进一步绘制其ROC曲线(图 1),计算AUC(表 2),结果显示,在HCC组与LC组、HCC组与HC组+CHB组+LC组、HCC组与CHB组+LC组中,AFP与GGT/AST联合诊断的AUC均显著高于AFP单独诊断的AUC(Z值分别为2.684、2.241、2.415,P值分别为0.007、0.025、0.016)。

    图  1  AFP与GGT/AST单独或联合检测诊断HCC的ROC曲线
    注:a,HCC组与CHB组; b,HCC组与LC组; c,HCC组与HC组+CHB组+LC组; d,HCC组与CHB组+LC组。
    表  2  AFP与GGT/AST单独或联合检测在辅助HCC诊断中的价值
    分组 标志物 AUC 95%CI 敏感度(%) 特异度(%) P
    HCC组vs CHB组 AFP 0.803 0.742~0.864 72.9 72.1 <0.05
    GGT/AST 0.789 0.717~0.861 67.4 83.8 <0.05
    联合 0.846 0.790~0.910 79.8 77.9 <0.05
    HCC组vs LC组 AFP 0.760 0.693~0.826 55.8 84.1 <0.05
    GGT/AST 0.727 0.650~0.803 90.7 46.4 <0.05
    联合 0.802 0.741~0.862 48.1 97.1 <0.05
    HCC组vs HC组+CHB组+LC组 AFP 0.835 0.791~0.879 86.0 68.2 <0.05
    GGT/AST 0.768 0.718~0.817 67.4 74.9 <0.05
    联合 0.843 0.802~0.885 73.6 78.5 <0.05
    HCC组vs CHB组+LC组 AFP 0.781 0.727~0.835 55.8 85.4 <0.05
    GGT/AST 0.758 0.700~0.815 67.4 77.5 <0.05
    联合 0.823 0.775~0.871 81.4 66.4 <0.05
    下载: 导出CSV 
    | 显示表格

    HCC的发生通常伴有前期的慢性HBV感染和肝硬化,在慢性HBV感染以及患有肝硬化的高危人群中,利用有效的筛查方式早期发现HCC至关重要,是患者可能获得根治的关键[7]。本文纳入352例研究对象,基于相关纳排标准将其分为4组,统计分析结果发现HCC组与HC组、CHB组、LC组AFP和GGT/AST比较,差异均有统计学意义(P值均<0.05),此结果与以往研究结果[8]相符。

    AFP作为最早被发现的蛋白肿瘤标志物之一[9],其可反映肝功能情况,因此广泛用于实验室检查。综合全球多种指南,AFP在我国可作为良好的血清学指标[10],但其特异度低,易引起误判[11]。在CHB、LC患者中AFP水平也会升高,因此鉴别诊断HBV相关HCC患者时,AFP具有一定局限性,且部分HBV相关HCC患者的AFP水平并未达到筛查标准,因此容易漏查[12]

    GGT在哺乳动物组织中广泛分布,是一种质膜结合蛋白,血清中的GGT主要来源于肝胆系统[13]。已有研究[14]表明GGT通过诱导DNA损伤来促进肿瘤进展和不良预后,释放活性氧以激活与入侵相关的信号通路,与HCC发展关联密切。AST主要分布于肝细胞线粒体内,当肝脏严重病变坏死时,血清中AST水平会显著升高[15],作为肝功能检查常用生化指标,GGT与AST在临床中应用广泛[16]。本研究计算GGT/AST比值并发现其单独或联合AFP时在HBV相关HCC的诊断中具有一定价值,且该指标计算简单,不用另增检验项目,便于在HCC诊断过程中应用。

    本研究ROC曲线分析结果显示,在HCC组与LC组中,GGT/AST联合AFP后AUC明显提高,表明GGT/AST与AFP联合在鉴别HCC与LC时有良好的诊断效果; 在HCC组与HC组+CHB组+LC组以及CHB组+LC组分别区别诊断时,二者联合的AUC均明显高于AFP单独诊断的AUC,进一步说明GGT/AST联合AFP在鉴别HCC与良性肝病患者中有较好的诊断价值。

    综上所述,本研究表明GGT/AST联合AFP在HBV相关HCC的临床诊断中具有一定价值,提高了AFP的单独诊断效率。由于本研究样本量较小,因此相关研究结果仍需未来增加样本量予以验证。

  • [1]
    CASULLI A, BARTH T, TAMAROZZI F. Echinococcus multilocularis[J]. Trends Parasitol, 2019, 35(9): 738-739. DOI: 10.1016/j.pt.2019.05.005.
    [2]
    WEN H, VUITTON L, TUXUN T, et al. Echinococcosis: Advances in the 21st Century[J]. Clin Microbiol Rev, 2019, 32(2): e00075-18. DOI: 10.1128/CMR.00075-18.
    [3]
    CAI H, GUAN Y, MA X, et al. Epidemiology of echinococcosis among schoolchildren in golog tibetan autonomous prefecture, qinghai, China[J]. Am J Trop Med Hyg, 2017, 96(3): 674-679. DOI: 10.4269/ajtmh.16-0479.
    [4]
    WANG J, GOTTSTEIN B. Immunoregulation in larval Echinococcus multilocularis infection[J]. Parasite Immunol, 2016, 38(3): 182-192. DOI: 10.1111/pim.12292.
    [5]
    GLATMAN ZARETSKY A, TAYLOR JJ, KING IL, et al. T follicular helper cells differentiate from Th2 cells in response to helminth antigens[J]. J Exp Med, 2009, 206(5): 991-999. DOI: 10.1084/jem.20090303.
    [6]
    HE L, GU W, WANG M, et al. Extracellular matrix protein 1 promotes follicular helper T cell differentiation and antibody production[J]. Proc Natl Acad Sci U S A, 2018, 115(34): 8621-8626. DOI: 10.1073/pnas.1801196115.
    [7]
    CROTTY S. T follicular helper cell biology: A decade of discovery and diseases[J]. Immunity, 2019, 50(5): 1132-1148. DOI: 10.1016/j.immuni.2019.04.011.
    [8]
    CROTTY S. T follicular helper cell differentiation, function, and roles in disease[J]. Immunity, 2014, 41(4): 529-542. DOI: 10.1016/j.immuni.2014.10.004.
    [9]
    SONG W, CRAFT J. T follicular helper cell heterogeneity: Time, space, and function[J]. Immunol Rev, 2019, 288(1): 85-96. DOI: 10.1111/imr.12740.
    [10]
    VINUESA CG, LINTERMAN MA, YU D, et al. Follicular helper T cells[J]. Annu Rev Immunol, 2016, 34: 335-368. DOI: 10.1146/annurev-immunol-041015-055605.
    [11]
    HELMOLD HAIT S, VARGAS-INCHAUSTEGUI DA, MUSICH T, et al. Early T follicular helper cell responses and germinal center reactions are associated with viremia control in immunized rhesus macaques[J]. J Virol, 2019, 93(4). DOI: 10.1128/JVI.01687-18.
    [12]
    XU W, ZHAO X, WANG X, et al. The Transcription factor tox2 drives T follicular helper cell development via regulating chromatin accessibility[J]. Immunity, 2019, 51(5): 826-839.e5. DOI: 10.1016/j.immuni.2019.10.006.
    [13]
    WANG B, LI H, SA RL, et al. The expression of ICOS in Tfh cells and the effect of ICOS blocker on the expression of IL-21 in Tfh cells with liver fibrosis[J]. Int J Immunol, 2020, 43(5): 483-487. DOI: 10.3760/cma.j.issn.1673-4394.2020.05.001.

    王波, 李慧, 萨茹拉, 等. 四氯化碳诱导肝纤维化小鼠Tfh中ICOS的表达及ICOS阻断剂对IL-21表达的影响[J]. 国际免疫学杂志, 2020, 43(5): 483-487. DOI: 10.3760/cma.j.issn.1673-4394.2020.05.001.
    [14]
    LINDQVIST M, van LUNZEN J, SOGHOIAN DZ, et al. Expansion of HIV-specific T follicular helper cells in chronic HIV infection[J]. J Clin Invest, 2012, 122(9): 3271-3280. DOI: 10.1172/JCI64314.
    [15]
    VELU V, MYLVAGANAM G, IBEGBU C, et al. Tfh1 cells in germinal centers during chronic HIV/SIV infection[J]. Front Immunol, 2018, 9: 1272. DOI: 10.3389/fimmu.2018.01272.
    [16]
    GLATMAN ZA, TAYLOR JJ, KING IL, et al. T follicular helper cells differentiate from Th2 cells in response to helminth antigens[J]. J Exp Med, 2009, 206(5): 991-999. DOI: 10.1126/sciimmunol.aan8884.
    [17]
    KLEIN F, MOUQUET H, DOSENOVIC P, et al. Antibodies in HIV-1 vaccine development and therapy[J]. Science, 2013, 341(6151): 1199-1204. DOI: 10.1126/science.1241144.
    [18]
    HANSEN DS, OBENG-ADJEI N, LY A, et al. Emerging concepts in T follicular helper cell responses to malaria[J]. Int J Parasitol, 2017, 47(2-3): 105-110. DOI: 10.1016/j.ijpara.2016.09.004.
    [19]
    DÍAZ A, CASARAVILLA C, ALLEN JE, et al. Understanding the laminated layer of larval Echinococcus Ⅱ: Immunology[J]. Trends Parasitol, 2011, 27(6): 264-273. DOI: 10.1016/j.pt.2011.01.008.
    [20]
    HOU YJ, ZHANG LQ, FAN HN. Research advances in circulating free DNA in liver cancer and liver-related parasitic diseases[J]. J Clin Hepatol, 2020, 36(2): 430-432. DOI: 10.3969/j.issn.1001-5256.2020.02.043.

    后亚军, 张灵强, 樊海宁. 循环游离DNA在肝癌和肝相关性寄生虫病中的应用进展[J]. 临床肝胆病杂志, 2020, 36(2): 430-432. DOI: 10.3969/j.issn.1001-5256.2020.02.043.
    [21]
    WANG ZX, GOU P, YU WH, et al. Measurement and bioinformatics analysis of exosomes microRNAs in bile of hepatic alveolar echinococcosis patients with biliary tract invasion[J]. J Clin Hepatol, 2020, 36(9): 2045-2049. DOI: 10.3969/j.issn.1001-5256.2020.09.027.

    王志鑫, 苟平, 于文昊, 等. 肝泡型包虫病侵及胆道患者胆汁外泌体microRNA的检测及生物信息学分析[J]. 临床肝胆病杂志, 2020, 36(9): 2045-2049. DOI: 10.3969/j.issn.1001-5256.2020.09.027.
    [22]
    DING JB, LI YJ, ZHANG FB. Research progress of hydatidosis immunity and vaccine[J]. J Xinjiang Med Univ, 2019, 42(1): 24-28. DOI: 10.3969/j.issn.1009-5551.2019.01.005.

    丁剑冰, 李玉娇, 张峰波. 包虫病免疫及疫苗的研究进展[J]. 新疆医科大学学报, 2019, 42(1): 24-28. DOI: 10.3969/j.issn.1009-5551.2019.01.005.
  • Relative Articles

    [1]Yuan WEN, Juanjuan ZHU. Clinical efficacy of double plasma molecular absorption system and sequential plasma exchange combined with continuous renal replacement therapy in treatment of acute-on-chronic liver failure with acute kidney injury[J]. Journal of Clinical Hepatology, 2024, 40(3): 556-561. doi: 10.12449/JCH240319
    [2]Jie LU, Dingchun LI, Ye LIU, Linna YUAN, Zhiwen DUAN, Wu LI. Clinical efficacy of low-dose plasma exchange combined with double plasma molecular absorption system/hemoperfusion in treatment of acute-on-chronic liver failure[J]. Journal of Clinical Hepatology, 2022, 38(11): 2526-2531. doi: 10.3969/j.issn.1001-5256.2022.11.017
    [3]Lan XiaoQin, Ji YaLi, Chen JinJun, Zhou FuYuan, Wen WeiQun. Effect of artificial liver support therapy on the short-term prognosis of patients with liver failure in the plateau stage: A stratified analysis based on Model for End-Stage Liver Disease score[J]. Journal of Clinical Hepatology, 2020, 36(9): 2005-2009. doi: 10.3969/j.issn.1001-5256.2020.09.019
    [4]Yao YunHai, Gan JianHe, Zhao WeiFeng. Effect of plasma exchange combined with continuous renal replacement therapy on the prognosis of patients with HBV-related acute-on-chronic liver failure and acute kidney injury[J]. Journal of Clinical Hepatology, 2019, 35(5): 1065-1069. doi: 10.3969/j.issn.1001-5256.2019.05.026
    [5]Guo XiJu, Guo WeiBo, Zhang JiaChang, Lu YaJing, Yang Yan. Clinical effect of double plasma molecular absorption system in treatment of liver failure due to hyperthyroidism: A case report[J]. Journal of Clinical Hepatology, 2018, 34(7): 1526-1528. doi: 10.3969/j.issn.1001-5256.2018.07.033
    [6]Wu YiChen, Yao HongYu, Wang KaiLi, Jiang QiYu, Liu Chang, Xing HanQian, Liu SuXia, You ShaoLi, Zhao Jun. Effect of plasma exchange on bioactivity of peripheral blood CD34+ cells in patients with acute-on-chronic (subacute) liver failure[J]. Journal of Clinical Hepatology, 2018, 34(11): 2383-2387. doi: 10.3969/j.issn.1001-5256.2018.11.023
    [7]Li Shuang, Chen Yu. Coping with shortage of plasma-The new therapeutic pattern of non-bioartificial liver[J]. Journal of Clinical Hepatology, 2017, 33(9): 1687-1692. doi: 10.3969/j.issn.1001-5256.2017.09.012
    [8]Zhou Jian, Wan Hong, Yang ZhengMao, Wang ZhaoXun. Clinical effect of plasma perfusion combined with plasma exchange in treatment of patients with acute-on-chronic liver failure[J]. Journal of Clinical Hepatology, 2017, 33(4): 715-718. doi: 10.3969/j.issn.1001-5256.2017.04.023
    [9]Hou HuanRong, Shang Jia, Kang Yi, Li YuKui, Ceng YanLi, Ding GangQiang, Mao ZhongShan, Xiao ErHui. Clinical effect of plasma exchange combined with hemofiltration in patients with subacute liver failure induced by antitubercular agents[J]. Journal of Clinical Hepatology, 2016, 32(2): 342-346. doi: 10.3969/j.issn.1001-5256.2016.02.030
    [10]Zhang LiangJie, Chen HuiJuan, Zhao ShouSong. Effects of artificial liver plasma exchange on cytokines in patients with liver failure[J]. Journal of Clinical Hepatology, 2015, 31(4): 578-581. doi: 10.3969/j.issn.1001-5256.2015.04.024
    [11]Wu ShaoHong, Gan JianHe, Huang XiaoPing, Lin Hua, Lu NianFang, Wu JiangQuan, Zheng RuiQiang. Clinical effect of albumin dialysis combined with plasma perfusion in treatment of liver failure[J]. Journal of Clinical Hepatology, 2014, 30(5): 434-437. doi: 10.3969/j.issn.1001-5256.2014.05.013
    [12]Liu XiaoHui, Guo HaiQing, Zhang Jing, Duan ZhongPing. Progress in technology and clinical application of non- bioartificial liver support system[J]. Journal of Clinical Hepatology, 2013, 29(9): 661-665. doi: 10.3969/j.issn.1001-5256.2013.09.007
    [13]You ShaoLi, Liu HongLing, Rong YiHui, Zhu Bing, Zang Hong, Liu WanShu, Wan ZhiHong, Mao PanYong, Xin ShaoJie. Preliminary investigation of hybrid bioartificial liver support system in treatment of HBV- related acute- on- chronic liver failure[J]. Journal of Clinical Hepatology, 2013, 29(9): 685-688. doi: 10.3969/j.issn.1001-5256.2013.09.013
    [14]Hu QiJiang, Jiang YingAn. Evaluation of the therapeutic efficacy of lamivudine combined with plasma exchange for treating acute-on-chronic hepatitis B liver failure [J]. Journal of Clinical Hepatology, 2013, 29(2): 107-109.
    [15]Zhou Jian, Wan Hong. Relationship between changes in serum cytokine levels after artificial liver therapy and clinical prognosis in patients with liver failure[J]. Journal of Clinical Hepatology, 2013, 29(7): 535-537. doi: 1001-5256 (2013) 07-0535-03
    [16]Zhang AiMin, You ShaoLi, Wan ZhiHong, Rong YiHui, Zhu Bing, Zang Hong, Xin ShaoJie. Combination therapy of plasma perfusion, plasma exchange, and entecavir in patients with hepatitis B acute-on-chronic liver failure[J]. Journal of Clinical Hepatology, 2012, 28(10): 744-747.
    [17]Zhang WenHua, Jia WenLing, Zhou ZiYing, Tang HaiTao, Wang FengMei. Investigation on the method and safety of the non-heparinized plasma exchange therapy in treating patients with hepatic failure[J]. Journal of Clinical Hepatology, 2012, 28(1): 50-52.
    [18]Liao JinMao, Li ZhuoRi, Hu XiaoXuan. The therapeutic effect of plasma exchange therapy in patients with severe hepatitis[J]. Journal of Clinical Hepatology, 2012, 28(4): 302-304.
    [19]Liu ZhiHong, Jiang JianNing, Luo GuangHan, Wu JiZhou, Deng YiMing, Su MingHua, Wu JianLin, Zhang Lu. The value of MELD score for evaluation of plasma exchange in patients with liver failure[J]. Journal of Clinical Hepatology, 2010, 26(6): 615-617.
  • Cited by

    Periodical cited type(3)

    1. 姚爱武,廖和壁,张璟. 血清AFP、AFP-L3与肝细胞癌经肝动脉化疗栓塞术后疗效的关系分析. 分子诊断与治疗杂志. 2023(04): 690-693+698 .
    2. 朱富平,刘红强,常清,冷伟业. miR-222-3p在乙型肝炎病毒相关肝细胞癌血清外泌体中的表达及临床意义. 局解手术学杂志. 2022(08): 702-708 .
    3. 高武林,韦超,郭晓烨. 术前血清MMP-9水平对HBV相关肝细胞癌患者肝切除术后生存的预测作用. 东南大学学报(医学版). 2022(05): 652-659 .

    Other cited types(2)

  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(3)  / Tables(2)

    Article Metrics

    Article views (1256) PDF downloads(40) Cited by(5)
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return