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1.
目的 探讨血管内皮生长因子(VEGF)、Eph受体酪氨酸激酶A2 (EphA2)、基质金属蛋白酶(MMP)-2和MMP-9在卵巢癌血管生成拟态中的作用.方法 收集临床和预后资料完整的卵巢癌组织标本84例,切片经明确诊断后进行CD31和过碘酸-雪夫 (PAS) 双重染色,证实肿瘤组织中存在血管生成拟态,行VEGF、EphA2、MMP-2和MMP-9 免疫组织化学染色,根据染色指数统计免疫组织化学染色结果.结果 有血管生成拟态组(36/84)和无血管生成拟态组卵巢癌组织(48/84)的VEGF、EphA2、MMP-9表达差异有统计学意义,有血管生成拟态组的卵巢癌细胞VEGF、EphA2、MMP-9表达明显高于无血管生成拟态组.但有血管生成拟态组和无血管生成拟态组患者的MMP-2表达差异无统计学意义.结论 在卵巢癌中血管生成拟态和内皮依赖性血管并存,VEGF、EphA2和MMP-9等参与了卵巢癌血管生成拟态的形成.检测VEGF、EphA2和MMP-9可作为预测卵巢癌预后的间接指标.  相似文献   

2.
目的 通过比较乳腺癌组织中血管内皮生长因子(VEGF)、环氧化酶-2(COX-2)、基质金属蛋白酶-9(MMP-9)三种蛋白的表达与乳腺癌超声重要征象的关系,初步探讨乳腺癌超声征象与分子病理学之间的关系,对乳腺癌患者的早期诊断、治疗及预后提供一定理论依据.方法 收集术后经病理证实的89例乳腺癌的标本,所有标本术前均用双盲法由从事多年乳腺超声诊断的医师按照BI-RADS分级法进行分组,同时每个病例均通过免疫组化法检测VEGF、COX-2、MMP-9的水平,分析VEGF、COX-2、MMP-9的表达与超声表现的相关性.结果 超声有毛刺征组乳腺癌VEGF、COX-2、MMP-9表达阳性率较无毛刺征组(P<0.05)明显增高.钙化组与无钙化组VEGF、COX-2、MMP-9表达阳性率无明显差异(P>0.05).有血管异常征组VEGF、COX-2、MMP-9表达阳性率较无血管异常征组(P<0.05)明显增高.淋巴结转移征组VEGF、COX-2、MMP-9表达的阳性率较无淋巴结转移征组(P<0.05)明显增高.结论 VEGF、COX-2、MMP-9的表达水平对乳腺癌超声征象的出现存在影响,并可作为乳腺癌超声征象中恶性征象的生物学基础,同时提示了有此类超声征象的乳腺癌预后差.  相似文献   

3.
目的 研究血清中microRNA-365表达水平对结肠癌组织中血管生成和癌细胞转移的影响.方法 选择2017年1月至2018年12月我院收治的120例结肠癌患者作为观察组,选择同时期来我院治疗的120例结肠良性肿瘤患者作为对照组.收集并比较两组患者基本资料,RT-PCR法检测患者血清中microRNA-365表达水平,ELISA法检测血清中影响肿瘤血管生成的血管内皮生长因子VEGF、基质金属蛋白酶MMP-2、MMP-9.结果 两组患者的性别、年龄相比均差异无统计学意义,两组具有可比性;观察组microRNA-365水平明显低于对照组(P<0.05),VEGF、MMP-2、MMP-9水平均明显高于对照组(P<0.05);观察组microRNA-365水平在不同年龄、不同性别、不同肿瘤大小的患者之间差异无统计学意义,肿瘤T分期较高、临床分期较高、出现转移的患者microRNA-365水平明显降低(P<0.05);观察组淋巴转移患者的microRNA-365水平明显低于无淋巴转移患者(P<0.05),VEGF、MMP-2、MMP-9水平均明显高于无淋巴转移患者(P<0.05),出现淋巴转移及肝转移患者的microRNA-365水平明显低于淋巴转移患者(P<0.05),VEGF、MMP-2、MMP-9水平均明显高于淋巴转移患者(P<0.05);microRNA-365水平与VEGF、MMP-2、MMP-9呈负相关.结论 结肠癌患者血清中microRNA-365表达水平下降,在结肠癌的诊断及预后中值得进一步研究.  相似文献   

4.
目的 通过检测血管内皮细胞生长因子(VEGF)、基质金属蛋白酶-9(MMP-9)、环氧化酶-2(COX-2)在乳腺癌细胞中的表达情况来探讨它们与乳腺癌淋巴结转移和微血管密度(MVD)的关系.方法 采用免疫组化SP法检测74例乳腺浸润癌(有淋巴结转移者39例,无淋巴结转移者35例)中VEGF、MMP-9、COX-2和CD34的表达,并用多因素Cox比例风险模型分析患者的预后.结果 VEGF、MMP-9、COX-2的表达与MVD值在淋巴结转移组与无转移组之间的差异均具有显著性(P<0.05),与乳腺癌淋巴结转移呈正相关;VEGF、MMP-9、COX-2蛋白表达与MVD值呈正相关(P<0.05);COX-2的表达随着乳腺癌病理分级的增高而增强;MVD值高者生存时间短.结论 乳腺癌VEGF、MMP-9、COX-2蛋白表达与其淋巴道转移和MVD有关,检测这几种蛋白表达将有助于判断乳腺癌的转移潜能、血管生成能力及预后.  相似文献   

5.
目的初步研究XAV939对人肝癌Hep G2细胞血管生成拟态形成的影响及其可能的机制。方法实验分为对照组和实验组(0.5和1μmol/L XAV939分别处理Hep G2细胞48 h);体外成管实验检测各组细胞形成血管拟态的能力,RT-PCR检测ZEB1及MMP-7 mRNA的表达,Western blot检测β-catenin、ZEB1和MMP-7蛋白的表达。结果对照组与实验组形成管状结构数目分别为9.67±0.70,5.67±0.64(0.5μmol/L)和2.27±0.81(1μmol/L),体外形成管道结构的数目减少(P0.01);实验组ZEB1及MMP-7 mRNA表达和ZEB1、MMP-7及β-catenin蛋白表达均较对照组减少(P0.05)。结论 XAV939能有效抑制人肝癌Hep G2细胞血管生成拟态的形成。  相似文献   

6.
乳腺良恶性组织中MMP-26表达及其与MMP-9、VEGF和MVD的关系   总被引:1,自引:0,他引:1  
目的 检测人乳腺良恶性组织中基质金属蛋白酶-26(matrix metalloproteinase-26,MMP-26)、基质金属蛋白酶-9(matrixmetalloproteinase-9,MMP-9)、血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达,计数微血管密度(micro vesseldensity,MVD),探讨4项指标与乳腺浸润性导管癌(infiltrating ductal carcinoma,IDC)临床病理指标的关系,分析MMP-26与MMP-9、VEGF表达的相关性及与MVD的关系.方法 采用免疫组化SP法,检测正常乳腺组织、普通型导管增生(usual ductalhyperplasia,UDH)、导管内原位癌(ductal carcinoma in situ,DCIS)和IDC组织中MMP-26、MMP-9、VEGF的表达并进行评分,以CD34标记肿瘤间质微血管,计数MVD.结果 (1)54例IDC中,MMP-26,MMP-9及VEGF表达的阳性率分别为62.96%、68.52%和75.93%;3种蛋白相关性分析显示:MMP-26与MMP-9表达呈正相关关系(F=0.32,P<0.05),MMP-26与VEGF表达未见相关性(F=0.23,P>0.05),MMP-9与VEGF表达呈正相关关系(F=0.44,P<0.01).(2)3种蛋白表达均与淋巴结转移密切相关(P<0.05),在其他各临床病理参数间差异未见显著性(P>0.05).(3)MMP-26阳性表达率随着MVD的增高而增高,但在高、低MVD组差异未见显著性(P>0.05),高MVD组MMP-9和VEGF阳性表达率明显高于低MVD组(P<0.05).结论 MMP-26在乳腺癌浸润、转移中发挥重要作用;MMP-26可能通过激活MMP-9参与肿瘤血管生成和促进肿瘤的侵袭和转移.  相似文献   

7.
目的研究胃腺癌中是否存在血管生成拟态(vasculogenic mimicry,VM)及其与MMP-2表达的关系,以及MMP-2表达的临床意义。方法收集121例胃腺癌标本及临床病例资料,利用CD34和PAS双重染色观察是否存在VM,然后对存在VM组和对照组进行MMP-2染色,分析VM与MMP-2表达的关系以及MMP-2表达与患者临床病理指标的关系。结果 121例胃腺癌中有44例(36.36%)存在VM。有VM组的MMP-2高表达的比例明显高于无VM组,两组之间的差异有统计学意义(P0.01)。伴有淋巴结转移的胃癌组织MMP-2高表达的比例显著高于无淋巴结转移的胃癌组织(P0.05)。结论胃腺癌中存在VM,MMP-2的高表达可能与VM形成及肿瘤淋巴结转移有关。  相似文献   

8.
目的观察血管内皮生长因子(VEGF)-C在卵巢上皮癌组织内的表达,分析VEGF-C的表达与癌临床病理特征和预后之间的关系,为临床抗淋巴管生成治疗肿瘤及评价患者预后提供理论依据。方法取人卵巢上皮癌组织蜡块78例和术后卵巢癌组织12例,免疫组化法和Western blot法观察VEGF-C在卵巢上皮癌组织内的表达情况。结果免疫组化结果显示VEGF-C蛋白主要表达于卵巢癌细胞胞浆内,VEGF-C在淋巴结转移组卵巢癌组织内的表达阳性率明显高于无淋巴结转移组(<0.01)。Western blot结果可见伴淋巴结转移卵巢癌组织内VEGF-C的表达水平高于无淋巴结转移卵巢癌组织。Kaplan-Meier和Cox回归分析表明,VEGF-C表达阴性患者的五年总体生存率和无瘤生存率均高于表达阳性患者。结论 VEGF-C表达与卵巢上皮癌淋巴结转移密切相关,可以作为判断卵巢上皮癌患者预后的新指标。  相似文献   

9.
目的:探讨血管内皮生长因子(Vascular endothelial growth factor,VEGF)和基质金属蛋白酶-7(Matrix metalloproteinase-7,MMP-7)在胆管癌组织中的表达及其预后的关系。方法:选取本院2010年5月至2012年8月手术切除胆管癌组织标本35例为观察组,非胆管癌组织标本(癌旁胆管组织)30例为对照组。利用免疫组织化学SP法检测在胆管癌组织及非胆管癌组织中VEGF和MMP-7的表达情况,分析其患者性别、年龄、病理分化、肿瘤大小、淋巴转移等临床特征之间的关系及其与预后的相关性。结果:(1)观察组VEGF和MMP-7的阳性表达率分别为68.57%、71.43%,对照组VEGF和MMP-7的阳性表达率分别为23.33%、36.67%,观察组中VEGF和MMP-7的阳性表达率均明显高于对照组(P0.05);(2)观察组VEGF以及MMP-7的阳性表达均与患者性别、年龄、肿瘤大小无关,而与分化程度及肿瘤的淋巴结转移有关(P0.05);(3)胆管癌患者术后5年总体生存率为22.86%(8/35),VEGF和MMP-7表达均与生存期5年相关(P0.05)。结论:VEGF和MMP-7在胆管癌组织中高表达,与胆管癌的分化程度及淋巴结转移关系密切,对胆管癌预后的评估具有重要的意义。  相似文献   

10.
VEGF和MMP-9在颅内动脉瘤中的表达及临床意义   总被引:1,自引:0,他引:1  
目的:探讨血管内皮生长因子(VEGF)和基质金属蛋白酶-9(MMP-9)在颅内动脉瘤组织中的表达及其在颅内动脉瘤形成、发展中的作用.方法:采用SP免疫组化法,检测18例颅内动脉瘤标本和9例正常脑动脉血管组织中VEGF和MMP-9的表达.结果:颅内动脉瘤组中,VEGF和MMP-9的平均吸光值显著高于对照组,相比较有统计学差异(P<0.05);颅内动脉瘤组VEGF和MMP-9阳性表达率分别为89.5%和84.2%,对照组无阳性表达,两组相比较有差异(P<0.05).结论:VEGF和MMP-9在颅内动脉瘤组织中有高表达,VEGF和MMP-9参与了颅内动脉瘤的形成和发展.通过检测VEGF和MMP-9的阳性表达可以为颅内动脉瘤的干预和治疗提供参考.  相似文献   

11.
Sun B  Qie S  Zhang S  Sun T  Zhao X  Gao S  Ni C  Wang X  Liu Y  Zhang L 《Human pathology》2008,39(3):444-451
Vasculogenic mimicry (VM) is the formation of fluid-conducting channels by highly invasive and genetically dysregulated tumor cells. In this study, we collected specimens of 84 human gastrointestinal stromal tumors (GISTs) along with clinicopathologic data and another 42 GISTs with fresh tissue that was used for gelatin zymography. VM was found in 21 of the 84 GISTs using CD31/periodic acid-Schiff double staining and CD117 and CD31 immunohistochemical staining. There was a significant difference in the VM-positive rate between the lesions with a mitotic rate > or =5/50 high-power fields and those with a lower mitotic rate (P = .000) and between the cases with and without liver metastasis (P = .008). There was a significant difference in the VM-positive rate between the high-risk group (5.9%) and the very low/low-risk group (12.5%) (P = .010) or the intermediate-risk group (39.5%) (P = .020). Kaplan-Meier survival analysis showed VM indicated a poor prognosis (P = .0000). Cox proportional hazards model indicated that the presence of VM, tumor size 10 cm or greater, and hemorrhage were independent predictors of a poor prognosis (P = .000, .005, .032, respectively). The staining indexes of matrix metalloproteinase (MMP)-2 and MMP-9 were higher in the VM-positive than in the VM-negative group (P = .024 and .037, respectively). Gelatin zymography showed that the activity of MMP-2 and MMP-9 was significantly higher in the VM-positive lesions (P = .013 and .033, respectively). We conclude that VM in GISTs is an unfavorable prognostic sign and that patients with VM-positive tumors are prone to suffer liver metastasis. Both MMP-2 and MMP-9 play an important role in VM formation in GISTs.  相似文献   

12.
目的: 探讨血管生成拟态 (vasculogenic mimicry, VM)与E-钙黏蛋白(E-cadherin, E-cad)在人卵巢上皮癌(epithelial ovarian cancer,EOC) 组织中的表达及意义。方法: 收集80例EOC标本和20例卵巢良性上皮性肿瘤标本,应用免疫组化法和组织化学法检测EOC和卵巢良性上皮性肿瘤组织中VM和E-cad的表达情况。结果: 在EOC和卵巢良性上皮性肿瘤组织中,VM和E-cad的阳性表达率分别为57.4%、0%和48.7%、75.0%,差异均显著(P<0.05或P<0.01);VM及E-cad的表达与EOC的组织学分级、腹腔脏器及淋巴结转移以及临床PTNM分期有关(P<0.05);VM与E-cad在EOC中的表达呈负相关(r=-0.578,P<0.01)。多因素分析:PTNM分期、腹腔脏器及淋巴结转移、VM和E-cad的表达是影响EOC根治术后患者预后的独立因素(P<0.05);VM阳性组与阴性组的5年生存率分别为4.3%和88.2%,E-cad阳性组与阴性组的5年生存率分别为71.8%和9.8%,差异均显著(P<0.05)。结论: 具有VM的EOC组织分化低,患者临床预后差;VM与E-cad的表达水平与EOC的发展及预后有一定的关系。  相似文献   

13.
Ovarian cancer is the most frequent cause of death from gynecologic cancer in the world. Current prognostic factors do not allow reliable prediction of response to chemotherapy and survival for individual ovarian cancer patients. Epidermal growth factor receptor (EGFR), E-cadherin, and matrix metalloproteinase (MMP)–9 are frequently studied in cancer; but their prognostic value in ovarian carcinoma remains unclear. In this study, we investigated the immunohistochemical expression of EGFR, E-cadherin, and MMP-9 in 120 cases of ovarian epithelial carcinoma; their relation to each other; their relation to histologic type, grade, and stage; and their relation to death rates after 3years of follow-up. Our results show that EGFR and MMP-9 were overexpressed extensively in high grades and advanced stages especially in nonserous carcinomas. E-cadherin was gradually lost in advanced cancers. There was a positive relation between the 3 antibodies and between them and the death rates. There is a strong relationship between EGFR and MMP-9, and this relation may occur by affecting E-cadherin. The present study provides a rationale for evaluating drugs that target these new pathways that may be promising in ovarian cancer treatment.  相似文献   

14.
We examined the expression levels of a number of metastasis-related genes to determine the relationship of these levels to the development of metastasis in renal cell carcinoma. Gene expression was examined in 46 formalin-fixed, paraffin-embedded, archival specimens of primary organ-confined, clear-cell, renal cell carcinoma from patients who had undergone radical nephrectomy. Twenty samples were from patients who did not have metastasis after a median of 48 months; 26 were from patients with either synchronous or metachronous metastases. Microvessel density was assessed by anti-CD-34 immunohistochemical analysis. The expression levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), matrix metalloproteinases (MMP)-2 and -9, and E-cadherin were examined at the periphery of the tumor by a colorimetric in situ mRNA. The expression levels of bFGF, VEGF, IL-8, MMP-2, and MMP-9 were significantly higher in primary renal tumors from patients with either synchronous or metachronous metastases than those who were disease-free at a median of 48 months of follow-up. Multivariate analysis of disease-free survival showed that the ratio of MMP-9 to E-cadherin (P = 0.012) and the expression level of bFGF expression (P = 0.045), were independent predictors for the development of metastases. The expression levels of bFGF, VEGF, and IL-8 did not correlate with microvessel density, which in itself was not a significant predictor of progression (P = 0.21). In summary, expression levels of genes that regulate metastasis angiogenesis can predict the metastatic potential in individual patients with organ-confined clear-cell renal carcinoma.  相似文献   

15.
《Acta histochemica》2022,124(1):151842
ObjectiveThis study aimed to explore the effects of knocking down both vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) on vasculogenic mimicry (VM) formation in choroidal melanoma (CM) cells.MethodsCell counting Kit (CCK)?8, monoclonal formation, wound healing, transwell and flow cytometry assays were used to observe the cell effects in CM cell line, ocular choroidal melanoma-1 cells (OCM-1) with respect to proliferation, migration, invasion and apoptosis. Three-dimensional (3D) cultures were also used to characterize VM tube structural effects in OCM-1 cells and western blotting was used to characterize protein expression changes in VM-related markers.ResultsDual VEGF/PDGF knockdown suppressed cell proliferation, migration and invasion, but promoted cell apoptosis. It also reduced VM tube structures in OCM-1 cells. VM associated markers including, VE-cadherin, EphA2 and MT1-MMP were also down-regulated in OCM-1 cells. Similarly, Wnt5a, β-catenin and phosphorylated-AKT levels were also down-regulated. Western blotting and 3D cultures further demonstrated that combined Wnt5a silencing with dual VEGF/PDGF knockdown significantly decreased VE-cadherin and EphA2 levels and reduced VM tube structures in OCM-1 cells.ConclusionsDual VEGF/PDGF knockdown suppressed cell growth and metastasis in OCM-1 cells, and blocked the Wnt5a/β-catenin/AKT signaling pathway thereby inhibiting VM formation.  相似文献   

16.
In the development and progression of hepatocellular carcinoma, tumor hypoxia plays an important role, as does activation of the Wnt pathway. The aim of this study was to characterize the expression and interrelationship between hypoxia and Wnt-pathway-associated proteins as prognostic factors for hepatocellular carcinoma. Expression of HIF-1α, CA-IX, E-cadherin, β-catenin, and Ki-67 was assessed by immunohistochemistry in 179 primary hepatocellular carcinoma cases. Univariate and multivariate analyses were performed to assess the relationship between the clinicopathological factors, protein expression, overall survival (OS), and recurrence-free survival (RFS). By univariate analysis, tumor stage, size, satellitosis, and vascular invasion were confirmed as prognostic factors for worse OS and RFS. High expression of HIF-1α, CA-IX, β-catenin, Ki-67, and E-cadherin was observed in 60, 15, 64, 8, and 64 % of tumors, respectively, and this was significantly associated with poor OS. CA-IX, HIF-1α, and E-cadherin were independent predictors of poor prognosis. We stratified 169 patients into four groups according to the expression level of hypoxia and Wnt pathway markers. The group with high expression of both hypoxia and Wnt-pathway-associated proteins showed worst OS. The poor survival of this group was also significant in patients with early stage disease and tumor size of less than 5 cm (p?<?0.05). We identified a subgroup of hepatocellular carcinoma patients with high expression of both hypoxia and Wnt pathway proteins and found this predictive of poor survival. The therapeutic options for this group might need to be revisited.  相似文献   

17.
目的 探讨基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制因子-1(TIMP-1)、血管内皮生长因子(VEGF)和转化生长因子β-1(TGFβ-1)表达与甲状腺乳头状癌和滤泡癌分化、浸润、转移的关系.方法 采用免疫组织化学EnVision法检测85例乳头状癌和59例滤泡癌中MMP-9、TIMP-1、VEGF和TGFβ-1的表达.结果 MMP-9、TIMP-1、VEGF、TGFβ-1表达于癌细胞的胞质,体现于阳性率和阳性强度两方面.乳头状癌在MMP-9、TIMP-1、VEGF和TGFβ-1的表达阳性率(83.5%、81.2%、90.6%和75.3%)和强度均低于或相近于滤泡癌(93.2%、86.4%、89.9%和78.0%).乳头状癌中有转移组的四种免疫学指标表达均高于无转移组;滤泡癌低分化型组在MMP-9、VEGF、TGFβ-1的表达均高于高分化型组,仅TIMP-1阳性率与阳性强度则显示相反表达.提示随两种癌分化程度的下降和出现转移MMP-9、TIMP-1、VEGF、TGFβ-1表达逐渐增高呈正相关关系,而且两种癌的VEGF、MMP-9表达均高于TIMP-1、TGFβ-1,后两者的阳件强度相对较低.结论 综合检测MMP-9、TIMP-1、VEGF和TGFβ-1四种免疫学指标,对探讨甲状腺乳头状癌和滤泡癌分化、浸润、转移和评估预后具有一定参考价值.  相似文献   

18.
E-cadherin and catenins play key roles in cell adhesion and motility. Little is known about the changes in expression of these molecules in the progression of ovarian carcinomas. In the present study, the immunohistochemical expression of E-cadherin and α-, β-, and γ-catenins was examined in 77 cases of ovarian carcinoma. In addition, the expression of these molecules was evaluated in 26 matched pairs of primary and metastatic lesions of advanced ovarian carcinomas. Of the 77 primary lesions, positive staining for E-cadherin and α-, β-, and γ-catenin was observed in 75 (97%), 63 (82%), 71 (92%) and 57 (74%) cases, respectively. Positivity for E-cadherin and α-, β-, and γ-catenin was significantly decreased in stage III and IV tumors compared with stage I and II tumors, suggesting that expression of the cadherin-catenin complex is reduced with the advancing stages of a tumor. Interestingly, expression of E-cadherin and α-, β-, and γ-catenin in the lesions of peritoneal dissemination was significantly increased compared with the primary lesions. These findings suggest that expression of the cadherin-catenin complex changes markedly and that reexpression may occur during the peritoneal dissemination of ovarian carcinoma cells.  相似文献   

19.
Aims: Primary peritoneal serous carcinoma (PPSC) is an unusual neoplasm that has not been properly characterized. To better define the clinicopathological and immunohistochemical features of PPSC, we present 6 such cases. Methods: The 6 patients consisted of one man and 5 women, ranging in age from 45 and 75 years. None of the patients had any history or clinical evidence of tumor elsewhere. The immunohistochemical profile was examined using antibodies against β-catenin, E-cadherin, wnt5a, EGFR, VEGF, vimentin, Ki67, and P53. Results: Of all the 6 PPSC cases, 5 cases presented stage IIIC and 1 case presented stage IV. Microscopically, 5 cases were poorly differentiated and 1 was moderately differentiated. All cases showed positive staining for β-catenin, E-cadherin, vimentin, VEGF, P53, and Ki67, 4 cases expressed EGFR, and all cases were consistently negative for wnt5a. Conclusions: We described 6 cases of PPSC with clinicopathological and immunohistochemical features. The findings provide basic knowledge of PPSC.  相似文献   

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