首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到19条相似文献,搜索用时 156 毫秒
1.
新生儿单纯乙型肝炎血源疫苗的免疫持久性和远期保护效果   总被引:13,自引:0,他引:13  
目的 掌握我国新生儿单纯接种乙型肝炎血源疫苗后的免疫持久性和远期预防效果;观察新生儿免疫较长时间后是否需加强免疫。方法 在湖南湘潭市等4个乙型肝炎疫苗试点区间,对1986-1988年出生并接种乙型肝炎血源疫苗的新生儿,连续14-15年按免疫儿年龄分层随机抽样采血随访,累计随访21680人次,观察免疫儿HBsAg、抗-HBs和抗-HBc的动态变化。结果 新生儿单纯乙型肝炎血源疫苗全程基因免疫后,在15年随访中没有加强免疫,各试点区免疫儿童HBsAg携带率低于1.66%,携带率没有随免疫后的延长而增加;阻断HBV慢性感染的效果持续在90%左右(95%可信限为:83.1%-97.2%);免疫后不同年限间HBsAg携带率、HBV感染率和保护效果差异均无显著性(P>0.05)。免疫儿抗-HBs阳性率随免疫后年限延长而逐年明显下降,至第9-10年下降为40%-50%,之后数年内下降幅度不大,至免疫后13-14年抗-HBs阳性率维持在30%-42%;抗-HBs滴度下降了90%。结论 新生儿单纯乙型肝炎疫苗接种后抗-HBs阳性率与滴度的下降不影响其远期预防效果;就群体而言,新生儿及时完成全程免疫后,无需加强免疫可有效阻断HBV感染后成为HBsAg慢性携带者,而很有可能终生受益。  相似文献   

2.
1978年先后在西非塞内加尔发现HBsAg阳性,而抗-HBc阴性的乙型肝炎患者,人体内单项抗-HBs阳性也不一定能保护机体免受HBV感染,从而表明了乙型肝炎疫苗免疫后所产生的高滴度抗-HBs不能防止一种新的乙型肝炎病毒感染。1987年将这种病毒命名为乙型肝炎病毒Ⅱ型(HBV_2)。我院于1992年~1996年对1800例乙型肝炎病人进行HBsAg、抗-HBs、HBeAg、抗-HBe、抗-HBc检测,现将结果报告如下。  相似文献   

3.
卫生部北京生物制品研究所从美国默克公司引进的重组酵母乙型肝炎疫苗生产技术,1992年开始按工业化生产要求进行生产线的安装、试运行,通过不断地消化先进技术,使其适合我国的条件,到目前为止,经过3年的努力,所生产的疫苗经中国药品生物制品检定所检定、国家新药评审委员会审评,认为达到了国家规定的标准,卫生部批准用于预防乙型肝炎。 重组酵母乙型肝炎疫苗可引发细胞与体液的免疫应答,有很高的预防效果。疫苗中所含的HBsAg,生物学性状稳定。该疫苗仅含有来源于DNA重组技术构建的酵母菌表达的HBsAg,不可能污染其它病毒,所以比血源乙肝疫苗更为安全。由于免疫原性好,可降低免疫剂量,每程免疫仅需5μg。母婴传播阻断效果更为显著,重组疫苗5μg,阻  相似文献   

4.
目的评价广州市长期应用乙型肝炎疫苗(hepatitis B vaccine,HepB)对乙型肝炎(乙肝)免疫防病效果。方法在广州市全市12个区、县级市按照多阶段分层整群抽样法,以家庭为单位对1~59岁人群进行横断面调查分析,包括检测HBsAg、抗-HBs,对HepB接种史及主要乙肝感染危险因素进行问卷调查,评估人群HepB接种率,分析和比较不同年龄组、不同家庭感染状况下接种与未接种HepB人群乙型肝炎病毒感染指标,评价HepB免疫防病效果。结果 1~16岁年龄组乙肝疫苗全程接种率为88.11%(2535/2877),17~59岁人群有乙肝疫苗免疫史为20.75%(470/2113)。在推行新生儿HepB接种纳入计划免疫管理后出生的1~16岁人群,HBsAg阳性率为1.29%,而出生时尚未开展HepB接种的20~59岁人群HBsAg阳性率为13.72%。1~16岁人群中有HepB接种史人群HBsAg阳性率0.99%,无接种史人群为5.56%,疫苗保护率为82.19%。20~59岁人群接种HepB,基本都不是在新生儿时期,疫苗保护率为52.01%。新生儿接种HepB,母婴乙肝传播阻断率为94.16%,并能有效阻断家庭内水平传播。结论长期实施新生儿接种HepB能控制、消除受种人群乙肝病毒感染,非新生儿人群接种HepB也能显著降低乙肝病毒感染率。  相似文献   

5.
目的 探讨细胞因子基因多态性与新生儿接种乙型肝炎疫苗后远期体液免疫应答水平的关系.方法 选取新生儿期按0、1、6月方案接种乙型肝炎疫苗,无加强免疫史,HBsAg和/或抗-HBc均阴性的293名儿童[平均(6.08±0.59)岁]为研究对象.83名抗-HBs <10 mIU/ml儿童为远期弱应答组(A组),210名抗-HBs≥10 mIU/ml为远期应答组(B组).采用PCR-限制性酶切片段长度多态性技术检测IL-1β、IL-2、IL-4、IL-10、IL-12B和IL-13基因11个多态性位点的基因型.结果 A组儿童IL-4基因-33T、-589T和2979T等位基因频率为86.1%、86.1%和90.4%,分别高于B组的76.0%、76.9%和83.3%(P均小于0.05).-33位和-589位紧密连锁,两位点基因型TT在A组的频率分别为74.7%和75.9%,高于B组的57.1%和59.0%(P均小于0.05);而基因型CT则相反,A组的频率为22.9%和20.5%,低于B组的37.6%和35.7%(P均小于0.05).IL-4基因2979位基因型和其他8个多态性位点的等位基因及基因型在两组儿童中的差异无统计学意义.结论 IL-4基因-33、-589和2979位的基因多态性可能与儿童在新生儿期接种乙型肝炎疫苗后远期体液免疫应答水平相关.  相似文献   

6.
目的:研究B7-H1蛋白疫苗对HBV转基因小鼠免疫应答的影响,探索治疗慢性乙型肝炎的新方法。方法:用不同剂量的乙型肝炎疫苗和B7-H1蛋白疫苗联合免疫HBV转基因小鼠,应用ELISA法检测转基因小鼠在不同时间点血清抗B7-H1抗体滴度,同时在免疫后第14周末处死小鼠取脾细胞,检测不同的免疫方法对小鼠脾细胞产生HBsAg特异性Th1类细胞因子(IFN-γ及IL-2)、对HBsAg特异性分泌IFN-γT细胞数量及对小鼠淋巴细胞增殖的影响。结果:成功完成小鼠的免疫计划,5周起血清中即能测到B7-H1抗体,同一时间点各组之间的抗体滴度值并无明显差异。加B7-H1蛋白免疫各组与相同剂量单用HBsAg蛋白免疫各组相比:IL-2均明显减低(P<0.05),分泌IFN-γT的T细胞数量下降,但脾淋巴细胞分泌IFN-γ的水平各组间无明显差异;MTT法测定的淋巴细胞增殖能力各组间也无明显变化。结论:B7-H1蛋白疫苗可诱导HBV转基因小鼠产生明显的抗B7-H1抗体应答,但不能增强抗HBsAg的免疫应答。较小剂量的HBsAg即可引起HBV转基因小鼠Th1类细胞因子(IFN-γ及IL-2)的分泌以及淋巴细胞增殖。  相似文献   

7.
目的 评价我国新生儿乙型肝炎(乙肝)疫苗免疫后的长期保护效果,为乙肝防控和乙肝疫苗HepB免疫策略提供参考.方法 用横断面调查和分层整群抽样的方法,在乙肝疫苗免疫效果观察监测点收集1987-1996年出生(13~22岁)、全程接种乙肝血源疫苗的人群,以及1997-2008年出生(1 ~ 12岁)、全程接种乙肝重组酵母疫苗人群的血清样本和资料;用微粒子酶免疫法检测HBV感染指标,结合本底资料和乙肝疫苗免疫史进行分析.结果 在河北正定、广西隆安、上海黄浦、青海同德和湖南湘潭5个监测点共收集1~12岁重组酵母疫苗免疫人群样本8133例,13 ~22岁血源疫苗免疫人群样本4848例,5个监测点的HBsAg平均阳性率均显著低于本底值,疫苗总体保护效果分别为86.04%~96.14%;河北正定、青海同德和湖南湘潭的年龄分布差异无统计学意义,广西隆安和上海黄浦的结果显示19~22岁人群HBsAg阳性率偏高;Anti-HBs阳性率随免疫年龄增长而下降,重组疫苗免疫人群从1~2岁组的86.84%下降至11~12岁组的46.40%,17 ~18岁组的Anti-HBs阳性率处于较低水平,而19~22岁组出现升高;几何平均浓度(GMC) <10 mIU/ml(Anti-HBs阴性)的比例随着年龄增长逐渐升高,100~999.99 mIU/ml和≥1000 mIU/ml的比例随着年龄的增长呈现下降趋势.结论 血源疫苗免疫后13~ 22年、重组酵母疫苗免疫后1~12年的总体保护效果良好;不必开展加强免疫,建议加强监测18岁以上人群的Anti-HBs水平,对GMC<10 mIU/ml者开展加强免疫.  相似文献   

8.
目的:比较乙型肝炎卡介苗联合疫苗与单价乙型肝炎疫苗的免疫效果。方法:实验动物采用豚鼠,按0、1、2月三针免疫程序接种,并于每针免疫后1个月采血,ELISA方法检测血清抗体滴度。实验分三部分进行。实验一:三种不同规格的联合疫苗与单价乙型肝炎疫苗的比较;实验二:同一规格连续三批联合疫苗与单价乙型肝炎疫苗的比较;实验三:联合疫苗与两种单价疫苗同时免疫的比较。结果:在三个实验中,联合疫苗组第一针血清抗体滴度均低于对照组,但无统计学差异:联合疫苗组第二、三针血清抗体滴度均高于对照组,也无统计学差异,实验组各组之间无明显差异。结论:联合疫苗组三针免疫程序的HBsAg的效力与单价乙型肝炎疫苗组相似。  相似文献   

9.
比较三种乙型肝炎血源疫苗和一种重组DNA(r-DNA)疫苗诱导Pre-S_2抗体阳性率与阻断乙型肝炎病毒母婴传播的有效率,其中rDNA疫苗不含有Pre-S_2蛋白,免疫后不产生Pre-S_2抗体,加热灭活疫苗按3μg与6μg两种剂量免疫后,半数以上对象均可产生Pre-S_2抗体,甲醛一步法灭活疫苗免疫后有30%婴儿产生Pre-S_2抗体。阻断母婴传播的有效率分别为:rDNA疫苗72.2%,甲醛一步法灭活疫苗70.1%,加热灭活疫苗3μg组35.6%,6μg组71.9%。疫苗免疫效果同HBsAg含量有关,似同Pre-S_2蛋白关系不明显。免疫后抗HBs阳性率与反映抗HBs含量的S/N值均同Pre-S_2抗体阳性率没有明显联系。Pre-S_2蛋白似非决定乙肝疫苗有效率的主要成分,而疫苗中的S蛋白含量对疫苗的免疫效果起十分重要作用。  相似文献   

10.
CCL20为CC家族的趋化因子,对未成熟DC和T细胞具有较强的正向趋化作用。HBsAg是乙肝病毒中具有保护作用的结构抗原。以HBsAg为目的抗原进行基因免疫可诱导HBV特异性免疫应答。为进一步增强基因疫苗的免疫效果,研究中,应用基因重组技术,构建CCL20和HBsAg的真核表达载体,将重组体用肌肉注射方式免疫C57BL/6小鼠,通过ELISA方法检测C57BL/6小鼠的抗-HBs抗体水平、淋巴细胞增殖试验检测抗原特异性Th活性、FACS检测CTL效应。结果显示,用CCL20/HBsAg真核表达质粒共注射免疫后,100%小鼠能在第4、6周检测到抗-HBs抗体,CCL20可显著增强HBsAg基因疫苗诱导的体液免疫应答;Th活性和CTL效应检测也显示,CCL20增强了HBsAg诱导的特异性细胞免疫反应。这将为新型乙肝疫苗的分子设计和研制提供新的理论与实践依据。  相似文献   

11.
A combined hepatitis A and B vaccine is available since 1996. Two separate open‐label primary studies evaluated the immunogenicity and safety of this hepatitis A and B vaccine (720 EI.U of HAV and 20 µg of HBsAg) in 306 healthy subjects aged 17–43 years who received three doses of the vaccine following a 0, 1, and 6 months schedule. These subjects were followed up annually for the next 15 years to evaluate long‐term persistence of anti‐HAV and anti‐HBs antibodies. The subjects whose antibody concentrations fell below the cut‐offs between Year 11 and Year 15 (anti‐HAV: <15 mIU/ml; anti‐HBs: <10 mIU/ml) were offered an additional dose of the appropriate monovalent hepatitis A and/or B vaccine. In subjects who received the additional vaccine dose, a blood sample was collected 1 month after vaccination. At the Year 15 time point, all subjects in Study A and Study B were seropositive for anti‐HAV antibodies and 89.3% and 92.9% of subjects in the respective studies had anti‐HBs antibody concentrations ≥10 mIU/ml. Four subjects (two in each study) received an additional dose of monovalent hepatitis B vaccine and mounted anamnestic responses to vaccination. No vaccine‐related serious adverse events were reported. This study confirms the long‐term immunogenicity of the three‐dose regimen of the combined hepatitis A and B vaccine, as eliciting long‐term persistence of antibodies and immune memory against hepatitis A and B for up to at least 15 years after a primary vaccination. J. Med. Virol. 84:11–17, 2011. © 2011 Wiley Periodicals, Inc.  相似文献   

12.
Features of occult hepatitis B infection in community‐based populations have yet to be described. In this study we documented: (1) the prevalence and demographics, (2) associated serology and viral loads, and (3) clinical outcomes of occult hepatitis B infection in community‐based populations. Hepatitis B surface antigen (HBsAg)‐negative sera collected from three Northern Canadian communities (HBsAg prevalences: 11–12%) in 1983–1985 were tested for HBV‐DNA by nested stage polymerase chain reaction. Of 706 HBsAg negative sera, 9 (1.3%) were HBV‐DNA positive. The median age of occult hepatitis B infected patients at the time of sampling was 9.8 years (range 3.1–50.4 years) and six (67%) were female. Two (22%) individuals were anti‐HBs positive (in the absence of prior vaccination). Viral loads were undetectable in all but two samples (2.40 and 2.86 log10 IU/ml). Only one of the five (20%) patients who were assessed clinically, remained HBV‐DNA positive at 25–30 year follow‐up. There was no clinical, biochemical or radiologic evidence of chronic hepatitis, cirrhosis or hepatocellular carcinoma in these individuals or on review of the charts from the remaining four infected patients. The results of this study suggest that in community‐based populations: (1) occult hepatitis B infection is not as common as HBsAg positive infection, (2) the majority of infected subjects are young females, (3) a minority are anti‐HBs positive, (4) viral loads are either undetectable or low, and (5) in the absence of concurrent liver disease, occult hepatitis B infection does not appear to be associated with long term adverse clinical outcomes. J. Med. Virol. 84:1369–1375, 2012. © 2012 Wiley Periodicals, Inc.  相似文献   

13.
The world's first nationwide hepatitis B virus (HBV) universal vaccination program for infants was launched in Taiwan in July, 1984. All infants received three to four doses plasma or recombinant HBV vaccines. In addition, infants of HBeAg-positive mothers received 0.5 ml of hepatitis B immunoglobulin within 24 hours after birth. The vaccination coverage rate is as high as 97%. Seroprevalence of hepatitis B surface antigen (HBsAg) declined from 9.8% (prevaccination period) to 0.6% in children in Taipei City after 20 years of mass vaccination. The seropositive rates for HBsAg, antibody to HBsAg, and antibody to hepatitis B core antigen were 1.2%, 50.5%, and 3.7%, respectively, in those born after the vaccination program (< 20 years old) in 2004. In line with the decrease of chronic HBV infection, the incidence of hepatocellular carcinoma (HCC) also decreased in children in Taiwan. From 1981 to 1994, the incidence of HCC in 6- to 9-year-olds declined from 0.52/100,000 for those born between 1974 and 1984 to 0.13 for those born between 1984 and 1986 (p < 0.001). We extended the observation to 2000, the incidence of HCC per 100,000 children declined from 0.54 to 0.20. The prevalence of a determinant mutants (amino acids 121–149 of HBsAg) in Taiwanese carrier children was 7.8% (eight out of 103) in 1984, increased to 19.6% (10 out of 51) in 1989, peaked at 28.1% (nince out of 32) in 1994, and remained stationary at 23.1% (three out of 13) and about 25% in 1999 and 2004, respectively; it was higher in those fully vaccinated compared with those not vaccinated. The other group of subjects who are susceptible to vaccine failure is the immunocompromized hosts. We observed some de novo HBV infection in children after liver transplantation. Despite of the success of hepatitis B immunization, childhood chronic HBV infection and HCC were not eliminated by the universal vaccination program. Among those HBsAg carriers born after the vaccination program, 89% of their mothers were found to be positive for HBsAg, indicating the importance of maternal transmission. This was also true in the mothers of children with HCC, of them 96% were HBsAg positive. After two decades of universal infant HBV vaccination, we found this program provides long-term protection for up to more than 20 years, and a universal booster is not required for the primary HBV vaccinees before adulthood. Mother-to-child transmission, although largely diminished, is still the main cause for immunoprophylaxis failure. The emergence of escape mutant did not impose increased risk of chronic infection at present. Nevertheless, development of new vaccines may overcome the vaccine failure.  相似文献   

14.
Long‐term persistence of vaccine‐induced immune response in adults was assessed annually for 15 years following primary immunization with a two‐dose inactivated hepatitis A vaccine. In 1992, 119 and 194 subjects aged 17–40 years and naïve for hepatitis A virus (HAV) were enrolled in two studies to receive 1,440 ELISA units (El.U) of inactivated hepatitis A vaccine (Havrix?, GlaxoSmithKline Biologicals, Belgium) according to a standard 0, 6 or an extended 0, 12 months schedule, respectively. Serum samples were taken 1 month after the second vaccine dose and every consecutive year up to 15 years after primary vaccination for measurement of anti‐HAV antibody concentrations (NCT00291876 and NCT00289757). At year 15, 100% (48/48) and 97.3% (108/111) of subjects vaccinated at 0, 6 or 0, 12 months remained seropositive for anti‐HAV antibodies, with geometric mean concentrations (GMCs) of 289.2 and 367.4 mIU/ml, respectively. An additional dose of HAV vaccine (1,440 El.U) was administered to the six subjects who had become seronegative for anti‐HAV antibodies since year 11. All subjects mounted a humoral immune response to the additional HAV challenge dose, although post‐challenge anti‐HAV antibody levels remained low in one subject. These studies represent the longest annual follow‐up of hepatitis A vaccine in healthy adults. The immune response induced by two doses of this inactivated HAV vaccine was shown to persist for at least 15 years. No difference in long‐term antibody persistence was observed between the two primary vaccination schedules, reinforcing the potential for flexibility in the timing of the second primary vaccine dose. J. Med. Virol. 83:1885–1891, 2011. © 2011 Wiley‐Liss, Inc.  相似文献   

15.
Vaccination with recombinant hepatitis B vaccines is highly effective in preventing hepatitis B infection. Recently, a preservative‐free (PF) formulation of hepatitis B vaccine [GlaxoSmithKline (GSK) Biologicals, Rixensart, Belgium] has been licensed. The immunogenicity of the PF hepatitis B vaccine and antibody persistence 6 years later was assessed in this study. This formulation was compared with the preservative‐ containing (PC) formulation of the vaccine and a low‐preservative (LP) content formulation. Five hundred forty‐one healthy adult subjects were evaluated in the primary study. Over 94% of the subjects in the three study groups had seroprotective anti‐HBs antibody concentrations (≥10 mIU/ml) 1 month after completing primary vaccination. Antibody measurements in 242 healthy adults who returned for the follow‐up study and who had received primary vaccination 6 years earlier showed that over 81% of subjects in the three study groups still had anti‐HBs antibody concentrations ≥10 mIU/ml. No apparent differences in antibody decline or distribution between the study groups were observed. These results indicate that the removal of preservatives from the hepatitis B vaccine does not affect adversely its immunogenicity both in the short and in the longer term. J. Med. Virol. 81:1710–1715, 2009. © 2009 Wiley‐Liss, Inc.  相似文献   

16.
目的 研究影响乙肝免疫效果的因素,探讨提高乙肝免疫预防效果的方法 .方法 使用巢式病例对照研究方法 ,以2006年全国乙肝等疾病血清流行病调查河北现场的1734名1-15岁儿童作为研究对象,按其HBsAg是否阳性分为病例组和对照组,分析造成儿童HBsA9阳性的危险因素.结果 母亲HBsAg阳性和儿童年龄、出生医院是影响乙肝疫苗预防效果的主要因素(P<0.0001).结论 当前乙肝免疫预防的工作重点在于发现HBsAg阳性孕妇,同时改进农村地区的新生儿乙肝免疫预防条件.  相似文献   

17.
A low dose of recombinant DNA hepatitis B vaccine (HB-VAX II, MSD) was tested for efficacy in the prevention of perinatal hepatitis B virus (HBV) transmission in normal and high-risk neonates born from HBsAg carrier mothers. A dose of 2.5 micrograms recombinant vaccine was injected intramuscularly at 0, 1, 2 and 12 months of age to 30 newborns from HBsAg negative mother (group I), 30 from HBeAg negative/HBsAg carrier mother (group II) and 30 from HBeAg positive/HBsAg carrier mother (group III). The incidence of persistent HBsAg carrier infants at 13 months of age was 0, 0, and 30.4 percent in groups I, II and III, respectively. The protective efficacy in high risk infants in group III was 65.7 percent. The seroconversion at month 4, after the third dose of vaccination was 96.3, 95.7 and 100 percent in group I, group II and group III, respectively. After a booster dose of vaccination at 12 months of age, the seroconversion rose to 100 percent at month 13 in all three groups. The geometric mean titer (GMT) of anti-HBs antibody at 13 months of age were 2,092, 1,657 and 1,938 mIU/ml in group I, group II and group III, respectively. It is concluded that the low dose (2.5 micrograms) recombinant hepatitis B vaccine using alone is effective in prevention of perinatal HBV transmission in low risk infants (groups I and II), but it is less effective in high risk infants (group III).(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

18.
目的 了解目前山东省社区人群乙型肝炎病毒(HBV)"a"抗原决定簇突变率和突变形式,探讨乙肝疫苗(HepB)接种对"a"抗原决定簇突变的影响.方法 在全省1~59岁社区人群中通过多阶段随机抽样确定调查对象,通过询问(15岁以上)或查阅接种记录(14岁以下)了解调查对象HepB免疫史;采集血标本,酶联免疫吸附方法 检测血清乙肝表面抗原(HBsAg),阳性者提取血清DNA,采用巢式PCR方法 扩增HBV S基因,测序后与标准序列进行比较.结果 共对7601人进行调查和血标本采集,得到HBsAg阳性标本239份(3.14%),可用于HBV DNA提取206份,扩增HBV S基因并成功测序102份.15份血清标本检测到13种HBV"a"抗原决定簇突变,突变率为14.70%(15/102).新生儿普种HepB前、后出生调查对象间,以及有、无HepB免疫史调查对象间"a"抗原决定簇突变率差异均无统计学意义.结论 目前山东社区人群中"a"抗原决定簇突变率较低且突变位点比较分散;未发现HepB接种对人群"a"抗原决定簇突变产生影响.  相似文献   

19.
This report concerns hepatitis B virus (HBV) infections observed in 155 infants from Senegal, studied with a view to determining the factors involved in development of the chronic carrier state. A chronic carrier state was observed in 50.3% of the infants. This study confirms that the risk of chronic carriage is linked to age. This risk declines very rapidly with age, falling from 82% in infants under 6 months old, to 15% in children between the ages of 2 and 3 years. Spontaneous elimination of hepatitis B surface antigen (HBsAg) is uncommon in HBsAg carriers during childhood. The difference observed in chronic carriage between males and females is due to a difference in susceptibility of the two sexes to the development of the chronic carrier state: HBV infections (before 2 years of age) lead to a chronic carriage in 77% of males as against 50% of females. These conclusions are important in view of the immunisation programs being carried out against hepatitis B virus in endemic areas. For a maximum efficacy, vaccination must be carried out at birth, or shortly afterwards.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号