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1.
目的探讨IFN诱导的粘病毒抵抗蛋白A(MxA)和真核细胞起始因子2α调节区2 (eIF-2α-reg2)基因的单核苷酸多态性(SNP)与CHB患者IFN治疗效果的关系。方法采用前瞻性研究方法,262例CHB患者签署知情同意书后予IFNα治疗12个月,随访至停药后6个月时评价疗效,分为持续应答和非持续应答。应用PCR及限制片段长度多态性的分析方法,检测患者MxA启动子-88、-123位点及eIF-2α-reg2的SNP,并比较SNP与IFN疗效的关系。结果262例CHB患者IFN治疗的应答情况为持续应答50例(19.1%),非持续应答212例(80.9%)。MxA启动子-88位点(G/T),GG型患者与GT型CHB患者IFN疗效比较,差异有统计学意义(OR 5.3,95%置信区间2.46~11.43,P<0.01);TT型与GT型患者的疗效比较,差异有统计学意义(OR 4.1, 95%置信区间1.86~9.09,P<0.01)。MxA启动子-123位点(C/A)、eIF-2α-reg2位点(A/G)各基因型及MxA启动子-88与-123组成4种可能的单体型患者IFN疗效比较,差异均无统计学意义(P>0.05)。结论MxA启动子-88位点为GT基因型的CHB患者对IFN治疗反应好,可作为IFN疗效的预测指标。  相似文献   

2.
目的:探讨干扰素(IFN)诱导抗病毒蛋白基因多态性对慢生丙型肝炎抗(CHC)病毒治疗疗效的影响.方法:168例CHC患者给予IFN:包括聚乙二醇IFN(PEGIFN)和普通IFN,联合利巴韦林治疗52、vk,随访26 wk,评价持续病毒学应答(SVR)情况.于基线时留取患者外周血标本,应用多聚酶链反应(PCR)检测病毒基因型,荧光定量聚合酶链反应法测定病毒载量,同时采用多聚酶链反应-限制片段长度多态性(PCR-RFLP)的分析方法,检测患者抗病毒蛋白的MxA-88,-123位点及eIF-2α-reg2的SNP.结果:CHC患者中GT型、TT型与GG型疗效比较,差异均有统计学意义(X2=6.862,P=0.012;X2=12.941,P=0.001).GT型与TT型的比较.差异不显著.CA型和AA型与CC型患者疗效比较,差异均有统计学意义(X2=5.818,P=0.020;X2=4.498,P=0.046).但CA型与AA型的比较,差异不显著.eIF-2α-reg2位点(A/G),基因型AA与基因型为AG或GG的患者IFN疗效比较,差异没有统计学意义.结论:MxA-88为TT或GT型比GG型患者对IFN反应性好.MxA-123为AA或AC型比CC型疗效好.eIF-2α-reg2位点基因型与CHC IFN疗效无相关性.  相似文献   

3.
目的探讨α-干扰素(IFN-α)诱导的黏病毒抵抗蛋白(MxA)和真核细胞起始因子调节区2(eIF-20α-reg2)基因的单核苷酸多态性(SNP)与慢性丙型肝炎(CHC)患者对IFN-α治疗应答的关系。方法前瞻性研究216例CHC患者,在接受IFN-α联合利巴韦林治疗48周,随访至停药后24周时,评价疗效[分为持续性应答(SVR)和非持续性应答(NSVR)]。应用多聚酶链反应(PCR)及限制性片段长度多态性(RFLP)法检测患者MxA启动子-88(G/T)、-123(C/A)及eIF-20α-reg2(MG)位点的SNP,并比较SNP与IFN疗效的关系。结果MxA 88位点:GT与GG型患者SVR(57.43%对34.21%)比较,差异有统计学意义(χ^2=9.37,P〈0.01);TT与GG型患者SVR(66.67%对34.21%)比较,差异有统计学意义(χ^2=9.37,P〈0.01)。而GT与TT型患者SVR比较(57.43%对66.67%),差异无统计学意义(χ^2=1.00,P〉0.05);MxA-123位点、eIF-20α-reg2位点基因型与IFN疗效比较:差异均无统计学意义(χ^2=4.87,P〉0.05;χ^2=1.66,P〉0.05)。多因素Logist回归分析结果显示:病毒载量(OR=3.178,95%CI:1.463~6.904,P=0.003)、干扰素种类(OR=3.117,95%CI:1.484~6.544,P=0.003)对SVR的独立影响具有统计学意义。MxA-88基因型(OR=1.470,95%CI:0.646~3.345,P=0.358)对SVR的独立影响无统计学意义。结论CHC患者MxA-88为TT或GT型者比GG型者对IFN-α应答好,但不是影响SVR的独立因素。  相似文献   

4.
都特  刘英 《中华肝脏病杂志》2005,13(12):957-959
1964年发现 A2G 小鼠能耐受对其它小鼠致死剂量的流感病 毒感染,这种特性是从小鼠16号染色体上单一显性等位基因遗 传获得的,因能抵抗副粘病毒(流感)而将其命名为 Mx 基因。 Mx~+细胞经干扰素(IFN)α处理后与 Mx 的差别是多出一条 7.5×10~4的多肽,而且这种蛋白只有在 IFN α/β诱导后产生, 即 Mx 蛋白。人类 Mx 蛋白分为 MxA 和 MxB,MxA 集中于 IFN  相似文献   

5.
目的探讨乙型肝炎病毒(HBV)自限感染和慢性感染与粘病毒抵抗基因-1(MxA)启动子的-88位点G/T单核苷酸多态性的关系。方法收集100例抗-HBs和抗-HBc阳性的HBV自限感染者和340例慢性感染者的外周全血,提出基因组DNA;采用竞争分化聚合酶链反应技术为基础的方法进行MxA-88G/T基因分型;采用单因素Odds ratio和x^2检验等方法进行统计学分析。结果MxA-88G/G基因型(低表达型)检出率为50.2%(221/440),T/T基因型(高表达型)检出率为5.5%(24/440),G/T杂合型检出率为44.3%(195/440)。与慢性感染患者相比,自限感染患者携带较低的G/G基因型(41.0%与52.9%,P〈0.05)、G等位基因(62.5%与75.3%,P〈0.01)和较高的T/T基因型(16.0%与2.4%,P〈0.01)、T等位基因(37.5%与24.7%,P〈0.01),而两者之间的G/T杂合型差异无统计学意义。结论MxA-88G/T基因型能在一定程度上影响HBV感染的自然转归,有望成为临床上HBV感染转归的预测指标。  相似文献   

6.
目的:探讨干扰素(IFN)-α/β受体启动子-408位点的单核苷酸多态性(SNP)与IFN疗效的关系。方法:应用聚合酶链反应(PCR)并基因测序法检测210例慢性乙型肝炎(CHB)患者(轻度38例、中度102例、重度70例)的IFN-α/β受体基因启动子-408位点的SNP。对210例中既往未用过IFN治疗的80例CHB患者给予聚乙二醇化干扰素α-2a or 2b(Peg-IFN-α-2a/2b)治疗48周。比较SNP与Peg-IFN疗效的关系。结果:80例患者中,IFN治疗持久应答(SR)33例(41.3%),非持久应答(NSR)47例(58.7%)。IFN-α/β受体启动子-408位点CT基因型患者干扰素治疗SR为65%(13/20),显著高于CC基因型患者干扰素治疗SR 29.5%(13/44),两者比较差异有显著性意义(χ2=7.166,P=0.007)。干扰素治疗SR组IFN-α/β-408位点等位基因C、T的频率与NSR组的频率比较差异无显著性意义(P>0.05)。结论:IFN-α/β受体启动子-408为CT杂合基因型的CHB患者可能对Pec-IFN治疗效果较好。  相似文献   

7.
目的 探讨程序性细胞凋亡基因-1(PD-1)单核苷酸多态性(SNP)与IFN-α治疗慢性乙型肝炎(CHB)患者发生早期病毒学应答的关系.方法 采用前瞻性队列研究方法,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析技术,检测135例中国汉族抗病毒初治CHB患者的PD-1.1和PD-1.2的SNP,并分析其与IFN-α早期病毒学应答的关系.分类变量资料采用x2检验.结果 135例CHB患者IFN-α治疗获得早期病毒学应答有33例,占24.4%.PD-1.1的AA、AG、GG基因型各占35、77和23例,IFN-α的早期病毒学应答各有5、25和3例,分别占14.3%、32.5%和13.0%(x2=6.258,P=0.044),AG基因型相对AA、GG基因型有较高的病毒学应答率(x2=6.246,P=0.012).在PD-1.2的AA、AG、GG基因型之间比较IFN-α的早期病毒学应答,差异无统计学意义(x2=3.957,P=0.138).结论 PD-1.1的SNP与中国汉族CHB患者IFN-α治疗早期病毒学应答有关.
Abstract:
Objective To investigate the relationship between the single nucleotide polymorphisms (SNP) of programmed cell death-1 (PD-1) gene and early virologic response of interferon-α (IFN-α) in patients with chronic hepatitis B (CHB). Methods A total of 135 CHB patients were prospectively enrolled in this study. SNP of PD-1.1 and PD-1.2 genes were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in these patients.Then its relationship with early virologic response to IFN-α treatment was analyzed. The data were analyzed by x2 test. Results Among the 135 patients, 33 (24.4%) achieved early virologic response to IFN-α. There were 35, 77, and 23 patients with AA, AG, GG genotgpe of PD-1.1. The early virologic response was achived in 5(14.3%), 25(32.5%) and 3(13.0%) among patients with AA,AG, GG genotypes of PD-1.1, respectively. There were statistically different (x2 = 6. 258, P =0. 044). The subjects with AG genotype showed higher response rate than those with AA or GG genotypes (x2 = 6. 246, P= 0. 012). However, the early virologic response rates were not significant different among subjects with AA, AG or GG genotype of PD-1. 2 ( x2= 3.957, P= 0. 138).Conclusion SNP of PD-1.1 gene may be used as a marker to predict the early virologic response to IFN-α treatment in Chinese CHB patients.  相似文献   

8.
Objective To investigate the relationship between the single nucleotide polymorphisms (SNP) of programmed cell death-1 (PD-1) gene and early virologic response of interferon-α (IFN-α) in patients with chronic hepatitis B (CHB). Methods A total of 135 CHB patients were prospectively enrolled in this study. SNP of PD-1.1 and PD-1.2 genes were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in these patients.Then its relationship with early virologic response to IFN-α treatment was analyzed. The data were analyzed by x2 test. Results Among the 135 patients, 33 (24.4%) achieved early virologic response to IFN-α. There were 35, 77, and 23 patients with AA, AG, GG genotgpe of PD-1.1. The early virologic response was achived in 5(14.3%), 25(32.5%) and 3(13.0%) among patients with AA,AG, GG genotypes of PD-1.1, respectively. There were statistically different (x2 = 6. 258, P =0. 044). The subjects with AG genotype showed higher response rate than those with AA or GG genotypes (x2 = 6. 246, P= 0. 012). However, the early virologic response rates were not significant different among subjects with AA, AG or GG genotype of PD-1. 2 ( x2= 3.957, P= 0. 138).Conclusion SNP of PD-1.1 gene may be used as a marker to predict the early virologic response to IFN-α treatment in Chinese CHB patients.  相似文献   

9.
Objective To investigate the relationship between the single nucleotide polymorphisms (SNP) of programmed cell death-1 (PD-1) gene and early virologic response of interferon-α (IFN-α) in patients with chronic hepatitis B (CHB). Methods A total of 135 CHB patients were prospectively enrolled in this study. SNP of PD-1.1 and PD-1.2 genes were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in these patients.Then its relationship with early virologic response to IFN-α treatment was analyzed. The data were analyzed by x2 test. Results Among the 135 patients, 33 (24.4%) achieved early virologic response to IFN-α. There were 35, 77, and 23 patients with AA, AG, GG genotgpe of PD-1.1. The early virologic response was achived in 5(14.3%), 25(32.5%) and 3(13.0%) among patients with AA,AG, GG genotypes of PD-1.1, respectively. There were statistically different (x2 = 6. 258, P =0. 044). The subjects with AG genotype showed higher response rate than those with AA or GG genotypes (x2 = 6. 246, P= 0. 012). However, the early virologic response rates were not significant different among subjects with AA, AG or GG genotype of PD-1. 2 ( x2= 3.957, P= 0. 138).Conclusion SNP of PD-1.1 gene may be used as a marker to predict the early virologic response to IFN-α treatment in Chinese CHB patients.  相似文献   

10.
目的探讨干扰素-γ(IFN-γ)启动子基因874位点的单核苷酸多态性(SNP)与IFNα-2b治疗慢性乙肝(CHB)持久应答的关系。方法选择CHB患者106例,应用PCR-SSP技术分析宿主的IFN-γ启动子基因874位点的SNP,患者给予IFNα-2b治疗1年,随访1年,比较SNP与IFNα-2b疗程结束时完全应答、停药后随访1年完全应答(持久应答)的关系。结果在标准疗程结束时,完全应答的患者中三种基因型的分布无统计学差异(χ2=3.594 9,P=0.165 7)。而在持久应答患者中三种基因型的分布有统计学差异,TT基因型患者的持久应答率高于其他两种基因型患者(χ2=6.639 8,P=0.036 1)。结论 CHB患者对IFNα-2b治疗的持久应答与IFN-γ基因型有一定关联性,尤其与TT基因型关联更大。  相似文献   

11.
目的 探讨白细胞介素-28B(IL-28B)基因多态性与慢性丙型肝炎(CHC)患者抗病毒治疗持续应答的关系. 方法 220例CHC患者均接受聚乙二醇干扰素联合利巴韦林治疗48周,随访至停药后24周.检测IL-28B (rs8099917)位点,根据测序结果将HCV感染者分为TT组、GG组、GT组.探讨IL-28B单核苷酸多态性和CHC患者抗病毒持续应答的关系. 结果 220例CHC患者中,182例(82.7%)疗程结束时获得病毒学应答(ETVR),TT组和GT+GG组获得ETVR的比例分别是93.5%和68.8%,两者差异具有统计学意义(x2=23.287,P<0.01);获得持续应答(SVR)的比例分别是86.2%和60.6%,两者差异具有统计学意义(x2 =15.531,P< 0.01).获得SVR患者中,TT组与GT+GG组的比值比(OR)为4.063,95%可信区间(CI)为1.972 ~ 8.369,x2=15.531,差异有统计学意义(P<0.01);在复发患者中,TT组与GT+ GG组的OR为0.246 (95%CI:0.119 ~ 0.507),x2=15.531,差异有统计学意义(P<0.01).结论 IL-28B (rs8099917)基因型与CHC患者抗病毒疗效密切,TT基因型患者较GT或GG型有更高的持续应答率及更低的复发率,可作为抗病毒疗效的一个重要预测因素.  相似文献   

12.
Hepatitis B virus (HBV) infection is still a public health problem worldwide, being endemic in some parts of the world. It can lead to serious liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular cancer. The differences in host immune response can be one of the reasons for the various clinical presentations of HBV infection. Polymorphisms of genes encoding the proinflammatory and antiinflammatory cytokines, which are responsible for regulation of the immune response, can affect the clinical presentation of the infection. Particularly, the polymorphisms of the genes encoding cytokines such as interleukin (IL)-1, IL-6, IL-8, IL-10, IL-18, IL-28B, interferon-γ, tumor necrosis factor-α, tumor growth factor-β1, and regulatory molecules like vitamin D receptor and chemokine receptor 5 can be responsible for different clinical presentations of HBV infections. The genomic information about cytokines and other mediators can be important for determining high-risk people for developing chronic hepatitis or hepatocellular cancer and may be used to plan treatment and preventive approaches for these people. In this review, the current knowledge in the literature on the association between cytokine/regulatory molecule gene polymorphisms and clinical course of chronic HBV infection is summarized, and the clinical implementations and future prospects regarding this knowledge are discussed.  相似文献   

13.
An insufficient cellular immune response seems to be critical for the immunopathogenesis of chronic hepatitis B virus infection.We have previously demonstrated no differences of T-lymphocyte subsets in blood between inactive hepatitis B s antigen(HBsAg) carriers and patients with HBeAg-negative chronic active hepatitis B.This study investigated the peripheral blood cytokine profile in patients with HBeAg-negative chronic active hepatitis B infection(Group A,n = 21) and inactive HBsAg carriers(Group B,n = 13).Serum cytokines [interferon(IFN)-γ,tumor necrosis factor-α,interleukin(IL)-1b,IL-4,IL-12,IL-10,IL-2,IL-5,IL-8] were analyzed by using flow cytometry.Patients with chronic active disease presented with significantly decreased levels of IFN-γ and IL-10 compared to inac-tive carriers(P = 0.048 and P = 0.008,respectively).In HBeAg-negative chronic active hepatitis B patients,a significant negative correlation of IFN-γ levels with serum hepatitis B viral load was noted(P = 0.021).In conclusion,patients with HBeAg-negative chronic active hepatitis B and HBsAg inactive carriers display a different cytokine profile.Decreased Th1 response observed in patients with chronic active hepatitis B could be implicated in the persistence of virus replication and ongoing progression of liver disease.  相似文献   

14.
目的 探讨重组酵母乙型肝炎疫苗治疗慢性乙型肝炎的疗效,确定合理剂量以用于更大样本的临床研究.方法 多中心、随机、双盲、安慰剂对照的临床试验.选择6个月内未经抗病毒治疗的慢性乙型肝炎患者216例,按1:1:1的比例采用分段随机方法分为90μg组、60μg组、安慰剂组,分别于0、2、6、10、14、18、22周肌内注射重组酵母乙型肝炎疫苗,每次90μg或60μg或安慰剂.所有患者均使用IFNα-1b 50μg,每周3次,治疗24周.停药后观察24周.定期检测患者HBVDNA、HBeAg及肝功能.酶联免疫斑点试验(ELISPOT)法检测部分患者产生IFN-γ的细胞数.结果 治疗24周时高剂量组、低剂量组和安慰剂组患者HBV DNA分别为(6.03±1.79)、(5.52±1.82)和(6.29±1.70)log10拷贝/mL(P=0.458);停药后24周HBV DNA分别为(5.92±1.98)、(5.49±1.99)和(6.16±1.76)log10拷贝/mL(P=0.720);治疗24周时,高剂量组、低剂量组及安慰剂组患者HBV DNA<1×105拷贝/mL分别占30.4%、39.4%和20.8%,低剂量组与安慰剂组比较差异有统计学意义(P=0.015);停药后24周,ttBV DNA<1×105拷贝/mL比例以低剂量组最高,但三组与治疗前比较差异无统计学意义(P=0.257).停药后24周,HBV DNA转阴率分别为17.4%、25.4%和6.9%,差异有统计学意义(P=0.012).治疗24周时及停药后24周,ALT复常率和HBeAg血清转换率以低剂量组最高,但三组比较差异无统计学意义.治疗24周时及停药后24周行ELISPOT试验显示,高剂量组、低剂量组ELISPOT阳性率比安慰剂组明显升高,差异有统计学意义(P<0.05).三组不良事件发生率相近,无一例发生药物相关的严重不良反应.结论 重组酵母乙型肝炎疫苗治疗对HBV有一定的抑制作用,合理剂量是60 μg.  相似文献   

15.
干扰素治疗慢性乙型肝炎的影响因素及疗效预测   总被引:2,自引:0,他引:2  
我国批准用于抗乙型肝炎病毒(HBV)治疗的药物共有两大类.包括普通干扰素(IFN)、聚乙二醇干扰素(PEG-IFN)以及数种核苷(酸)类似物(NAs).  相似文献   

16.
目的 探讨白细胞介素17 (IL-17)单核苷酸多态性(SNPs)及血浆水平与慢性HCV感染的关系.方法 选择慢性丙型肝炎(CHC)患者228例,健康体检者81例.TaqMan探针法检测IL-17 rs8193036及rs2275913位点基因多态性,酶联免疫吸附法检测血浆IL-17水平,分析CHC患者IL-17等位基因、基因型及血浆水平与健康人群的差异.结果 CHC患者组与健康对照组IL-17 rs8193036位点C、T等位基因及rs2275913位点A、G等位基因分布比较,P值均>0.05,差异均无统计学意义.CHC患者组与健康对照组的IL-17 rs8193036位点基因型CC (46.49%对比41.98%)、CT (45.61%对比44.44%)、TT(7.89%对比13.58%)分布比较,P值均>0.05,差异均无统计学意义;rs2275913位点基因型AA(16.23%对比13.58%)、AG (48.25%对比50.62%)、GG(35.53%对比35.80%)分布比较,P值均>0.05,差异均无统计学意义.HCV基因1型与2型感染CHC患者IL-17 rs8193036及rs2275913位点等位基因及基因型分布比较,P值均>0.05,差异均无统计学意义.CHC患者组血浆IL-17水平为(97.67±39.68) pg/ml显著高于健康对照组的(71.60±19.78)pg/ml,两组比较t=2.414,P=0.033,差异有统计学意义.结论 IL-17高水平表达在HCV感染及慢性化中发挥重要作用,而IL-17 rs8193036及rs2275913位点SNPs可能与HCV易感性及持续感染无明确关系.  相似文献   

17.
目的 探讨乙型肝炎e抗原(HBeAg)阳性的慢性乙型肝炎(CHB)患者在用替比夫定(LDT)治疗期间Th1/Th2型细胞因子水平的动态变化情况及其与治疗转归的关系.方法 收集接受LDT治疗的15例HBeAg阳性CHB患者在基线与治疗4、8、12、24、48周时的外周血,用流式细胞仪对其血清白细胞介素(IL)-2、-4、-6、-10,以及肿瘤坏死因子(TNF)α与干扰素(IFN)γ的表达水平进行动态检测;比较完全应答组,部分应答组、无应答组、病毒学突破组及各组在不同治疗时间点的Th1/Th2型细胞因子水平.对数据的统计学分析用重复测量设计方差分析与Spearman相关分析. 结果完全应答组的Th1型细胞因子水平高于部分应答组、无应答组及治疗中病毒学突破组;而Th2型细胞因子水平则低于其他各组,但各组之间的差异无统计学意义(P>0.05).在完全应答组内IL-2、TNF α及IFN γ水平自服用LDT 12周起及其后各时间点较基线时明显升高,差异具有统计学意义(P<0.05);部分应答组内从服药24周起IFN γ水平较基线时升高(P<0.05);无应答组在服药48周时IL-6及IL-10水平较基线时明显升高(P<0.05);在病毒学突破组自服药24周起的IL-4水平及服药12周起的IL-6水平与基线相比,逐渐升高,且差异具有统计学意义(P<0.05).结论 Th1/Th2型细胞因子的活性平衡与LDT治疗HBeAg阳性CHB患者的转归有一定相关性,这可能与LDT治疗对CHB患者的免疫应答有一定程度的恢复作用有关.  相似文献   

18.
目的 探讨转化生长因子(TGF)-β1单核苷酸多态性(SNP)与慢性HBV感染的关系.方法 采用PCR方法,对74例慢性乙型肝炎患者、41例乙型肝炎肝硬化患者和41例健康人外周血细胞基因组DNA的TGF-β1基因中三个SNP位点(rs2241715、rs2241716、rs4803455)进行基因分型.数据分析采用χ2或Fisher精确概率法检验.结果 健康人的 rs2241715基因型及等位基因频率与慢性乙型肝炎和肝硬化患者相比,差异有统计学意义(χ2=11.419,P<0.01或χ2=6.218χ2=5.961;P<0.05),rs2241715 T/T基因型的个体患慢性乙型肝炎和乙型肝炎肝硬化的相对危险度分别为其他型的2.974倍(95%CI=1.209~7.314,P=0.018)和3.228倍(95%CI=1.201~8.675,P=0.020),rs2241716和rs4803455位点则无上述相关性.结论 TGF-131基因的rs2241715 SNP位点T/T基因型可能与慢性HBV感染密切相关.  相似文献   

19.
影响HBV感染/清除及抗病毒疗效的因素极为复杂,如宿主、病毒、环境等。近年来研究证明白细胞介素(IL)28B基因多态性与HCV清除及抗病毒治疗高度相关,国内外许多学者开始关注IL-28B基因变异在慢性乙型肝炎(CHB)中的作用,其中rs12979860、rs12980275、rs8099917 3个位点成为研究热点。总结了IL-28B基因多态性在HBV感染/清除及CHB患者干扰素治疗中的作用,虽然尚无定论,但目前认为IL-28B基因多态性可能在CHB领域中具有重要的潜在临床价值。  相似文献   

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