首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 15 毫秒
1.
目的 探讨 5 氨基乙酰丙酸 (5 ALA)诱导荧光光动力学诊断对膀胱肿瘤早期诊断的价值。 方法  34例血尿患者行 5 ALA诱导荧光染色膀胱镜检及活组织检查 :以 5 ALA缓冲液灌注膀胱 ,2~ 3h后 ,用D LIGHT系统进行荧光膀胱镜检 ,对荧光阳性区域及白光下肉眼观有异常但荧光阴性的区域进行活检。活检结束后行经尿道电切术 (TUR)。 结果  31例呈荧光阳性 ,其中 2 6例为尿路上皮癌 ,5例为良性病变 ;3例呈荧光阴性 ,其中腺性膀胱炎 2例 ,出血性膀胱炎 1例。 11例移行细胞癌患者于癌旁或远处发现普通膀胱镜下无法识别的微小荧光阳性区域 ,经活检均证实有肿瘤存在 ,其中 2例为原位癌。 6 1处活检结果经统计分析 ,该诊断方法对膀胱肿瘤的灵敏度为 97.6 %(4 1/ 4 2 ) ,特异性为 4 7.4 % (9/ 19)。 结论  5 ALA诱导荧光光动力学诊断对膀胱肿瘤诊断有较高价值 ,能发现早期肿瘤 ,同时可彻底进行电切除。  相似文献   

2.
PURPOSE: We determined whether neoplastic disease, which was missed under white light can be found during transurethral resection of bladder cancer by 5-aminolevulinic acid-induced porphyrin fluorescence. MATERIALS AND METHODS: 5-Aminolevulinic acid-induced fluorescence endoscopy was carried out in 328 cases. A 3% 5-aminolevulinic acid solution was instilled intravesically in a mean time of 2.8 h before endoscopy. The fluorescence was excited by a special incoherent light source which provided blue light in addition to white light. RESULTS: In 82 (25%) cases additional neoplastic lesions were found only because of their red porphyrin fluorescence which was induced by 5-aminolevulinic acid. 31% of these neoplastic foci which were found in normal and nonspecific inflamed mucosa had a poorly differentiated histology. CONCLUSIONS: 5-Aminolevulinic acid facilitates detection of neoplastic disease during transurethral resection of bladder cancer and increases the accuracy of diagnosis.  相似文献   

3.
The use of a photodynamic fluorescence marker for diagnosis of tumors is an intriguing concept to improve the thoroughness of surgical tumor resection. Complete surgical resection of multifocal bladder tumors and flat lesions such as carcinoma in situ is known to be difficult, and thus a source of recurrences. We report on the recent experience with the intravesical application of the photosensitizer prodrug 5-aminolevulinic acid (5-ALA), which is a nontoxic physiological heme substrate. Initial results from fluorescence diagnosis using krypton laser light, and recent results with a modified incoherent light source constantly showed a 25% increase in urothelial tumor detection in comparison to white light endoscopy. Due to the high sensitivity, the number of biopsies could be decreased constantly in comparison to routine random biopsies taken under white light endoscopy. The results show about 25-30% of cases with fluorescent lesions which are histologically benign. 5-ALA is a promising tool for the diagnosis of bladder cancer. The outcome of the admission study for 5-ALA in urology in Germany is positive, and is being continued by prospective multicenter clinical studies to prove the hypothesis of reduction of tumor recurrence with this method. 5-ALA-based fluorescence endoscopy is strongly recommended for further clinical testing. Copyright Copyright 1999 S. Karger AG, Basel  相似文献   

4.
目的:研究5-氨基乙酰丙酸(5-ALA)诱导荧光光动力学对膀胱肿瘤的早期诊断价值。方法:对血尿患者行5-ALA诱导荧光膀胱镜检查及活组织检查,以5-ALA膀胱灌注,2h后采用D-light光源系统进行膀胱镜检,对荧光阳性区域及白光下肉眼可见异常但荧光阴性区域进行活检,活检后行经尿道膀胱肿瘤电切术。结果:31例患者中有4例荧光阴性且普通光肉眼观阴性者未活检。余27例患者共取活检96处,其中荧光阳性区域取活检89处(包括普通光肉眼观阴性区域35处),切缘取活检7处。病理检查结果显示:尿路上皮癌65处,阳性率为73.03%(65/89),非肿瘤性病变24例,假阳性率为27%(24/89),切缘活检7处为阴性。荧光下阳性而白光下阴性的肿瘤位点11处,切缘活检7处均为阴性。结论:5-ALA诱导荧光光动力学诊断对膀胱肿瘤有较高价值,能发现早期肿瘤,同时进行电切将更彻底。  相似文献   

5.
The use of a photodynamic fluorescence marker for diagnosis of tumors is an intriguing concept to improve thoroughness of surgical tumor resection. Complete surgical resection of multifocal bladder tumors and flat lesions as carcinoma in situ is known to be difficult, and thus a source of recurrencies. We report on the recent experience with the intravesical application of the photosensitizer prodrug 5-aminolevulinic acid (5-ALA), which is a nontoxic physiological heme substrate. Initial results from fluorescence diagnosis using krypton laser light and recent results with a modified incoherent light source constantly showed a 25% increase in urothelial tumor detection compared with white light endoscopy. Because of the high sensitivity, the number of biopsies could be decreased constantly compared with routine random biopsies taken under white light endoscopy. The results show about 25% to 30% of cases with fluorescent lesions, which are histologically benign. 5-ALA is a promising tool for diagnosis of bladder cancer. The outcome of the initial study of 5-ALA in urology in Germany is positive and is continued by prospective multicenter clinical studies to prove the hypothesis of reduction of tumor recurrence with this method. 5-ALA-based fluorescence endoscopy is strongly recommended for further clinical testing.  相似文献   

6.
PURPOSE: Endoscopy done under fluorescence induced by 5-aminolevulinic acid has proved to be a procedure with high sensitivity for detecting transitional cell carcinoma of the bladder. In this multicenter, parallel group, phase III study we compared 5-aminolevulinic acid fluorescence endoscopy guided transurethral bladder resection with transurethral bladder resection done using only white light endoscopy. The proportion of tumor-free resected cases in the 2 groups was evaluated. MATERIALS AND METHODS: After patient stratification according to participating centers and European Organization for the Research and Treatment of Cancer risk score 65 and 64 were randomized to the 5-aminolevulinic acid fluorescence and white light endoscopy groups, respectively. Residual tumor was evaluated in the 2 groups by repeat transurethral resection 10 to 14 days later. Analysis was performed according to the intent to treat principle with all patients randomized, followed by per protocol analysis. RESULTS: Intent to treat analysis revealed that in the white light endoscopy group 40.6% of cases were resected tumor-free at primary resection, whereas with 5-aminolevulinic acid fluorescence endoscopy guided transurethral resection 61.5% were resected tumor-free (p <0014). On protocol analysis 46.9% patients in the white light and 67.3% in the 5-aminolevulinic acid fluorescence endoscopy groups were resected tumor-free (p <0.031). No difference was noted in the 2 groups in regard to side effects or laboratory findings. CONCLUSIONS: The risk of residual tumor after transurethral resection of transitional cell carcinoma is significantly decreased by 5-aminolevulinic acid fluorescence endoscopy.  相似文献   

7.
目的 探讨窄光成像诱导光动力学检查对膀胱肿瘤早期诊断的应用价值. 方法 应用高清窄光成像膀胱镜系统对28例血尿患者进行膀胱镜检,术中分别对普通光下及窄光下的可疑部位膀胱黏膜组织活检,普通光组取样35处,窄光组取样79处(含普通光35处,普通光镜下疑似者窄光均显示镜下疑似,不重复取样)送病理检查.比较窄光取样组和普通光取样组肿瘤检出敏感性.结果 窄光取样组活检病理报告尿路上皮癌32处(21例),其中原位癌11处,腺性膀胱炎5处(2例),良性病变(炎性病变)3处(2例),正常黏膜4处(3例).普通光取样组尿路上皮癌17处(15例),腺性膀胱炎2处(1例),无原位癌.活检病理阳性32处,窄光组病理阳性32处,肿瘤检出率100%(32/32);普通光组病理阳性17处.肿瘤检出率53%(17/32);膀胱肿瘤及原位癌检出率2组比较差异有统计学意义(P<0.01).共取样79处,其中窄光组阳性32处,敏感性41%(32/79);普通光组阳性17处,敏感性22%(17/79),2组肿瘤取样敏感性比较差异有统计学意义(P<0.01). 结论 窄光成像膀胱镜能提高对膀胱肿瘤特别是原位癌的诊断敏感性,降低术中残存率,减少膀胱肿瘤复发危险性.  相似文献   

8.
PURPOSE: Photodynamic therapy after intravenous injection of Photofrin (QLT Phototherapeutics, Vancouver, British Columbia, Canada) results in a contracted bladder and skin photosensitivity, which limits its clinical application. In an attempt to overcome these limitations photodynamic therapy after intravesical instillation of Photofrin or 5-aminolevulinic acid (ALA) in an orthotopic rat bladder tumor model was explored and compared with intravenous Photofrin for photodynamic therapy efficacy and phototoxicity. MATERIALS AND METHODS: At 2 weeks after bladder implantation of 1.5 x 10(6) AY-27 tumor cells animals were randomly grouped. Photofrin was administered (5 mg./kg. intravenously and 2 mg./ml. intravesically). The ALA concentration for intravesical instillation was 300 mM. Whole bladder photodynamic therapy with graded doses of light (lambda = 630 nm.) was performed 4 hours after drug administration. Tumor control and complications were evaluated. RESULTS: Photodynamic therapy with intravenous Photofrin plus 100 J./cm.(2) light resulted in severe bladder damage. Of 10 rats 6 died and 2 of the 10 that received 50 J./cm.(2) died. There were no photodynamic therapy related deaths in groups receiving intravesical instillation of Photofrin or ALA that also received 50 to 100 J./cm.(2) Median survival in rats treated with ALA intravesically plus 75 J./cm.(2) (77 days), Photofrin intravesically plus 50 (67) or 100 J./cm.(2) (76) and Photofrin intravenously plus 50 J./cm.(2) (60) were significantly different from that in controls (44). CONCLUSIONS: Intravesical instillation of Photofrin or ALA can achieve the same photodynamic therapy efficacy as intravenous Photofrin in this orthotopic rat bladder tumor model with less phototoxicity to normal tissues.  相似文献   

9.
OBJECTIVE: Photodynamic diagnosis (PDD) for the detection of bladder cancer has become a diagnostic tool in several hospitals. Several studies have reported different rates of false positive biopsies using 5-aminolevulinic acid induced fluorescence. In this study we evaluated the effect of previous intravesical therapy on the false positive biopsy rate. METHODS: Two hours prior to endoscopy 1.5g ALA dissolved in 50ml 1.4% NaHCO(3) solution was instilled intravesically. For fluorescence excitation a blue light source (D-light, Karl Storz) was used. Under white and fluorescence light guidance, tumor locations were recorded, cold cup biopsies were taken and tumors were resected. Patients were divided into 3 groups, last intravesical therapy (IVT) less than 6 months prior to PDD, last IVT longer than 6 months before PDD and no previous IVT. RESULTS: In total 917 biopsies were taken in 249 procedures of fluorescent and non-fluorescent areas. White light endoscopy revealed 270 and PDD 378 of in total 390 tumors, resulting in a sensitivity of 97% and specificity of 49% for PDD. Pathologic evaluation considered 270 fluorescent biopsies as false positive. The rate of false positive biopsies was 25.7% in the group No IVT, 30.6% in the group PDD-IVT >6 months, whereas in the group "within 6 months after intravesical therapy" the rate was 39.6% (p<0.025). When premalignant lesions such as dysplasia II are considered tumor the difference between the groups is even more significant (p<0.001). CONCLUSIONS: The procedure has a high sensitivity for superficial bladder cancer and decreases the number of overlooked lesions. Recent intravesical therapy results in significantly more false positive fluorescent biopsies. Since patient outcome might predominantly be determined by the early detection and subsequent treatment of (pre)malignant tissue we suggest that PDD is justified even shortly after intravesical therapy.  相似文献   

10.
Objectives. To use 5-aminolevulinic acid (5-ALA) in diagnostic cystoscopy and during transurethral resection of the bladder (TURB) to treat transitional cell carcinoma. The efficacy of this new technique was compared with standard cystoscopy.Methods. The 5-ALA, instilled in the bladder 2 hours before cystoscopy, makes the pathologic tissue fluorescent when illuminated with blue light (375 to 400 nm). This allows a better recognition of the neoplastic forms for both diagnostic and therapeutic purposes during TURB. This method has been used since May 1997 on 49 patients in whom bladder tumor was diagnosed either immediately or during postchemotherapy follow-up.Results. One hundred seventy-nine biopsies were taken of fluorescent and nonfluorescent areas (3.5 per patient) to check the effectiveness of the new method compared with standard cystoscopy. A good correlation was found between 5-ALA cystoscopy and the histopathologic diagnosis, with a good sensitivity (87%). The 5-ALA cystoscopy allowed the diagnosis of a tumor in 24 patients with negative standard cystoscopic findings. Furthermore, 5-ALA cystoscopy detected 7 cases of carcinoma in situ. Neither local nor systemic (because of endovesical instillation) side effects were noted.Conclusions. We believe that 5-ALA could be routinely used in the diagnosis of superficial bladder tumors, as it was shown to improve the diagnostic sensitivity for carcinoma in situ and to reduce the risk of recurrence related to missed cancerous lesions or incomplete TURB.  相似文献   

11.
The treatment of Klebsiella pneumoniae, particularly extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae, is currently a great challenge. Photodynamic antimicrobial chemotherapy is a promising approach for killing antibiotic-resistant bacteria. The aim of this study was to evaluate the capacity of 5-aminolevulinic acid (5-ALA) and its derivative 5-ALA methyl ester (MAL) in the presence of white light to cause photodynamic inactivation (PDI) of K. pneumoniae planktonic and biofilm cells. In the presence of white light, 5-ALA and MAL inactivated planktonic cells in a concentration-dependent manner. Biofilms were also sensitive to 5-ALA and MAL-mediated PDI. The mechanisms by which 5-ALA and MAL caused PDI of ESBL-producing K. pneumonia were also investigated. Exposure of K. pneumonia to light in the presence of either 5-ALA or MAL induced cleavage of genomic DNA and the rapid release of intracellular biopolymers. Intensely denatured cytoplasmic contents and aggregated ribosomes were also detected by transmission electron microscopy. Scanning electron microscopy showed that PDI of biofilms caused aggregated bacteria to detach and that the bacterial cell envelope was damaged. This study provides insights into 5-ALA and MAL-mediated PDI of ESBL-producing K. pneumoniae.  相似文献   

12.
目的:探讨5-氨基乙酰丙酸(5-ALA)荧光膀胱镜的应用对非肌层浸润性膀胱癌术后早期复发率的影响。方法:将90例非肌层浸润性膀胱癌患者随机分为两组,每组45例,分别在白光膀胱镜和5-ALA荧光膀胱镜下行TURBt,术后6周所有患者均行5-ALA荧光膀胱镜检查以观察肿瘤复发情况,并对复发肿瘤行二次TURBt。结果:行二次TURBt后,90例患者中,25例(27.7%)发现有肿瘤发生,其中自光膀胱镜组18例(40%),荧光膀胱镜组7例(15.5%),两组间比较差异有统计学意义(P=0.05)。结论:5=ALA荧光膀胱镜对膀胱肿瘤的诊断和治疗具有较高价值,可以显著降低非肌层浸润性膀胱癌术后早期复发率。  相似文献   

13.
PURPOSE: Several investigators have demonstrated an approximately 20% higher tumor detection rate by 5-aminolevulinic acid (ALA) fluorescence endoscopy compared to standard white light cystoscopy, and suggested a reduction in tumor recurrences when fluorescence endoscopy was performed as standard procedure during transurethral resection. We test this hypothesis. MATERIALS AND METHODS: In a prospective randomized multicenter study 102 patients underwent transurethral resection of bladder tumor(s) either with white light or ALA fluorescence assisted endoscopy. A second look transurethral resection with ALA fluorescence endoscopy was performed 6 weeks after the initial operation. RESULTS: At second look transurethral resection tumor was detected in 20 of 51 patients (39%) in the white light group and in 8 of 51 (16%) in the ALA fluorescence endoscopy group. This difference was statistically significant (p = 0.005). CONCLUSIONS: ALA fluorescence endoscopy is an innocuous and inexpensive diagnostic procedure that significantly improves bladder tumor detection rates compared to standard white light endoscopy. In our controlled study ALA fluorescence endoscopy reduced the residual tumor detection rate at second look transurethral resection by 59%.  相似文献   

14.

Purpose

We determined whether the sensitivity of detecting dysplasia or early bladder cancer can be improved by 5-aminolevulinic acid induced porphyrin fluorescence.

Materials and Methods

A 3 percent 5-aminolevulinic acid solution was instilled intravesically before cystoscopy in 104 patients. The 5-aminolevulinic acid induced porphyrin fluorescence was excited by violet light from a krypton ion laser (wavelength 406.7 nm.).

Results

The sensitivity of the fluorescence cystoscopy (96.9 percent) was significantly (p less than 0.0001) greater than that of white light cystoscopy (72.7 percent). There was no impact on specificity.

Conclusions

Due to the high sensitivity of the procedure fluorescence guided biopsies are recommended instead of random biopsies.  相似文献   

15.
PURPOSE: 5-Aminolevulinic acid induced fluorescence endoscopy has outstanding sensitivity for detecting early stage bladder cancer. Nevertheless, a third of the lesions that show specific fluorescence are histologically benign. We decreased the false-positive rate of 5-aminolevulinic acid induced fluorescence endoscopy by incorporating protoporphyrin IX fluorescence quantification into the standard cystoscopy procedure. MATERIALS AND METHODS: In 25 cases (53 biopsies) of a history of or suspicion for bladder cancer 5-aminolevulinic acid induced fluorescence endoscopy and fluorescence image quantification were performed. For fluorescence image quantification images obtained with a target integrating color charge-coupled device camera were digitized and stored in a personal computer. Red-to-blue ratios were calculated from fluorescence positive lesions and results were correlated with hematoxylin and eosin histology. RESULTS: Malignant fluorescence positive lesions showed significantly stronger fluorescence intensity than fluorescing lesions with benign histology. A threshold was established that decreased the false-positive rate by 30% without affecting sensitivity. CONCLUSIONS: Fluorescence image quantification is a new endoscopic method for objectively selecting multicolor fluorescence bladder lesion images for biopsy. It has the potential of eliminating human error by different surgeons with variable experience in fluorescence endoscopy.  相似文献   

16.
PURPOSE: We describe the technique of fluorescence image guided optical coherence tomography (FG-OCT). We examined its ability to enhance specificity and sensitivity for the noninvasive diagnosis of early bladder cancer. MATERIALS AND METHODS: Transitional cell carcinoma was developed in 54 Fisher 344 female rats by intravesical methyl-nitroso-urea instillations. Two or three rats were diagnosed sequentially by 5-ALA (5-aminolevulinic acid hydrochloride) induced fluorescence imaging, cross-sectional OCT and histological microscopy weekly during weeks 11 to 33 following initial methyl-nitroso-urea instillation to track the course of carcinogenesis. RESULTS: The specificity of fluorescence detection was significantly enhanced by FG-OCT (53% and 93%, respectively, p <0.0001). The sensitivity of fluorescence detection and FG-OCT was 79% and 100%, respectively. CONCLUSIONS: FG-OCT cystoscopy has the potential to diagnose early bladder cancer with high sensitivity and specificity with drastically decreased imaging time compared to that of white light guided OCT cystoscopy.  相似文献   

17.
18.
OBJECTIVE: The fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) is a well established method for the treatment of brain tumor, especially malignant glioma. However, there is no report on photodynamic diagnosis (PDD) for spinal tumor. In the present study, we evaluated the usefulness of PDD for spinal ependymoma using 5-ALA. METHODS: Three patients with spinal ependymoma received oral doses of 5-ALA (20 mg/kg body weight) 2 hours before anesthesia induction. Intraoperatively, fluorescence was observed with a 420 nm sharp cut filter after excitation with a violet semiconductor laser (405 nm) and was verified by analysis of fluorescent spectra. Residual fluorescent samples taken from the tumor cavity were examined histologically RESULTS: Fluorescence peaked at 636nm in the removed tumors in all cases. Fluorescent tissue tended to exist at the cranial and caudal portion in the tumor cavity or around the anterior median fissure. The residual fluorescent tissue was not detected after removal of the tumor in case 1. The residual fluorescent tissue was composed of tumor cells and ependymal lining in case 2 or the infiltrated inflammatory cells and vascular endothelial cells in case 3. Postoperative magnetic resonance (MR) imaging showed no residual tumor in any of the cases. CONCLUSION: The results of this study indicate the usefulness of 5-ALA-induced tumor fluorescence in guiding resection of spinal ependymoma. 5-ALA-induced porphyrin fluorescence may label spinal ependymomas easily and clearly enough to enhance the completeness of tumor removal.  相似文献   

19.
PURPOSES: Fluorescence diagnosis induced by 5-aminolevulinic acid enables more thorough transurethral resection of superficial bladder carcinoma compared with conventional white light. We performed a prospective, single institution, randomized trial to investigate whether the residual tumor rate and long-term tumor recurrence can be decreased by fluorescence diagnosis. MATERIALS AND METHODS: A total of 301 patients underwent transurethral resection of bladder tumors with white light or fluorescence diagnosis. Transurethral resection was repeated 5 to 6 weeks later to evaluate the residual tumor rate. To determine recurrence-free survival patient followup was performed every 3 months by white light cystoscopy and urine cytology. Recurrence-free survival was analyzed via Kaplan-Meier methods and multivariable Cox regression analysis. RESULTS: A total of 191 patients with superficial bladder carcinoma were available for efficacy analysis. The residual tumor rate was 25.2% in the white light arm versus 4.5% in the fluorescence diagnosis arm (p <0.0001). Median followup in the white light arm in 103 cases was 21.2 months (range 4 to 40) compared with 20.5 (range 3 to 40) in the 88 in the fluorescence diagnosis arm. Recurrence-free survival in the fluorescence diagnosis group was 89.6% after 12 and 24 months compared with 73.8% and 65.9%, respectively, in the white light group (p = 0.004). This superiority proved to be independent of risk group. The adjusted hazard ratio of fluorescence diagnosis versus white light transurethral resection was 0.33 (95% confidence interval 0.16 to 0.67). CONCLUSIONS: Fluorescence diagnosis is significantly superior to conventional white light transurethral resection with respect to the residual tumor rate and recurrence-free survival. The differences in recurrence-free survival imply that fluorescence diagnosis is a clinically relevant procedure for decreasing the number of tumor recurrences.  相似文献   

20.
目的观察5-氨基乙酰丙酸(5-ALA)介导的光动力学治疗对裸鼠人胃癌移植瘤的治疗作用。探索5-ALA介导的光动力学(PDT)治疗胃癌的可能机制。方法以MGC-803人胃癌细胞制备裸鼠人胃癌移植瘤模型:整体荧光成像系统下观察动物瘤体发出的荧光信号:测量荷瘤对照组、单纯激光组、单纯5-ALA组和5-ALA介导的PDT治疗组治疗后第1、3、7、14、21天的裸鼠肿瘤大小并计算肿瘤体积:末次测量后切除肿瘤行病理检查和透射电镜观察,TUNEL法检测组织细胞凋亡。结果常规方法培养MGC一803人胃癌细胞并接种裸鼠.可以成功制备出裸鼠人胃癌移植瘤的模型:荷瘤裸鼠肿瘤组织在特定波长的荧光激发下可发出特有的红色荧光。荷瘤对照组、单纯激光组、单纯5-ALA组和5-ALA介导的PDT治疗组治疗后第1、3、7、14、21天4组间的肿瘤体积差异有统计学意义(肚1003.086,P=0.000),PDT治疗组明显小于其他3组;病理检查提示.PDT治疗后肿瘤细胞大片凝固性坏死;透射电镜观察提示,PDT治疗组肿瘤组织存在大量死亡细胞及部分凋亡细胞:TUNEL法检测发现,PDT治疗组的肿瘤组织凋亡指数显著高于其他3组(χ^2=18.237.P=0.000)。结论5-ALA介导的PDT对于裸鼠人胃癌移植瘤具有明显的治疗效果.而单纯给予5-ALA或激光辐射对肿瘤无明显抑制作用;肿瘤细胞的坏死及凋亡是5-ALA介导的PDT产生细胞毒作用的重要机制。  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