1.Preliminary exploration of the efficacy and safety of darolutamide in the treatment of metastatic hormone-sensitive prostate cancer
Zekun XIN ; Shuyu ZHANG ; Yuqiang SHI ; Zhentao LEI ; Kai LE ; Jie XIONG ; Lin YANG ; Shenghan WANG ; Qiang GAO ; Bao ZHANG
Chinese Journal of Urology 2025;46(3):188-191
Objective:To investigate the efficacy and safety of darolutamide in the treatment of patients with metastatic hormone-sensitive prostate cancer.Methods:A retrospective analysis was conducted on 17 cases of prostate cancer patients who received treatment with darolutamide in combination with ADT at our hospital from January to December 2022. The median age was 70 (range: 56 to 92) years old. The median pre-treatment prostate-specific antigen (PSA) level was 63.50 (range: 29.16 to 700.74) ng/ml. Sixteen cases had a Gleason score of 8 or above, and 11 cases were classified as high tumor burden (with four or more bone metastases and/or visceral metastases). The patients were treated with darolutamide in combination with goserelin (10.8 mg, subcutaneous injection, every 12 weeks). The decrease in PSA levels was observed at 2 weeks and at 1, 2, 3, and 6 months post-treatment. The time to achieve a 50% decrease in PSA level (PSA50), a 90% decrease (PSA90), and a PSA level of ≤0.2 ng/ml was recorded.Adverse drug reactions were also documented.Results:All the 17 patients were followed up and continued to receive darolutamide at our center without any loss to follow-up. The median follow-up time was 11.4(8.9, 15.3)months. It showed a median PSA decrease from baseline of 83.33% at 2 weeks, 95.37% at 1 month, 96.71% at 2 months, 97.22% at 3 months, and 99.10% at 6 months. The median time to achieve PSA50, PSA90, and PSA ≤ 0.2 ng/ml were 1.3 (0.9, 1.7)months, 1.7 (1.2, 2.4)months, and 3.6 (2.9, 4.5)months respectively. Six patients with bone metastases experienced relief of metastatic lesions after treatment. Only one patient developed papules on the left upper limb, which were assessed as grade 1 rash, and the rash disappeared after three days treatment of topical application of hydrocortisone cream.Conclusions:Darolutamide could rapidly control and significantly reduce PSA levels in prostate cancer patients, with a favorable safety profile.
2.A prediction model of targeted biopsy for PI-RADS 4-5 based on mp-MRI and PSAD
Yibo LI ; Pan ZANG ; Lei DING ; Zhentao TANG ; Chao LIANG ; Jie LI
Journal of Modern Urology 2025;30(7):565-570,575
Objective To construct a prediction model for targeted biopsy(TB)of the prostate based on multiparameter magnetic resonance imaging(mp-MRI)and prostate-specific antigen density(PSAD)to predict the outcomes TB in patients with a score of 4-5 on the Prostate Imaging Reporting and Data System(PI-RADS).Methods Clinical data of 669 patients with PI-RADS 4-5 receiving transperineal TB in our hospital during Jan.2022 and Dec.2023 were retrospectively analyzed.The data were divided into the training set and validation set with a ratio of 2∶1.Independent predictors of TB results were identified with univariate and multivariate logistic regression to construct a formula for the prediction model.A prediction model was subsequently constructed and validated using the validation set to assess its efficacy and predictive performance with the area under the receiver operating characteristic curve(AUC).The relative importance of each independent predictor in the formula was analyzed.Results Univariate and multivariate logistic regression analyses showed that age,total number of lesions,histological location,PI-RADS score and PSAD were significantly associated with the TB outcomes(P<0.05)and could be used as independent predictors,with PI-RADS score and PSAD making the highest contribution to outcome prediction,accounting for 27.59%and 37.58%,respectively.The training set had an AUC of 0.840(95%CI:0.800-0.881),which was more predictive than other single predictors,and the high-risk group based on the optimal threshold of 0.833 increased the positive biopsy rate from 79.3%to 94.4%.The validation set had an AUC of 0.865(95%CI:0.810-0.920),and the high-risk group based on the optimal threshold of 0.594 increased the positive biopsy rate from 80.0%to 96.2%.Conclusion The prediction model has good predictive ability for lesions with PI-RADS 4-5,which can significantly improve the positive detection rate and reduce a large number of unnecessary systematic puncture.
3.A prediction model of targeted biopsy for PI-RADS 4-5 based on mp-MRI and PSAD
Yibo LI ; Pan ZANG ; Lei DING ; Zhentao TANG ; Chao LIANG ; Jie LI
Journal of Modern Urology 2025;30(7):565-570,575
Objective To construct a prediction model for targeted biopsy(TB)of the prostate based on multiparameter magnetic resonance imaging(mp-MRI)and prostate-specific antigen density(PSAD)to predict the outcomes TB in patients with a score of 4-5 on the Prostate Imaging Reporting and Data System(PI-RADS).Methods Clinical data of 669 patients with PI-RADS 4-5 receiving transperineal TB in our hospital during Jan.2022 and Dec.2023 were retrospectively analyzed.The data were divided into the training set and validation set with a ratio of 2∶1.Independent predictors of TB results were identified with univariate and multivariate logistic regression to construct a formula for the prediction model.A prediction model was subsequently constructed and validated using the validation set to assess its efficacy and predictive performance with the area under the receiver operating characteristic curve(AUC).The relative importance of each independent predictor in the formula was analyzed.Results Univariate and multivariate logistic regression analyses showed that age,total number of lesions,histological location,PI-RADS score and PSAD were significantly associated with the TB outcomes(P<0.05)and could be used as independent predictors,with PI-RADS score and PSAD making the highest contribution to outcome prediction,accounting for 27.59%and 37.58%,respectively.The training set had an AUC of 0.840(95%CI:0.800-0.881),which was more predictive than other single predictors,and the high-risk group based on the optimal threshold of 0.833 increased the positive biopsy rate from 79.3%to 94.4%.The validation set had an AUC of 0.865(95%CI:0.810-0.920),and the high-risk group based on the optimal threshold of 0.594 increased the positive biopsy rate from 80.0%to 96.2%.Conclusion The prediction model has good predictive ability for lesions with PI-RADS 4-5,which can significantly improve the positive detection rate and reduce a large number of unnecessary systematic puncture.
4.Preliminary exploration of the efficacy and safety of darolutamide in the treatment of metastatic hormone-sensitive prostate cancer
Zekun XIN ; Shuyu ZHANG ; Yuqiang SHI ; Zhentao LEI ; Kai LE ; Jie XIONG ; Lin YANG ; Shenghan WANG ; Qiang GAO ; Bao ZHANG
Chinese Journal of Urology 2025;46(3):188-191
Objective:To investigate the efficacy and safety of darolutamide in the treatment of patients with metastatic hormone-sensitive prostate cancer.Methods:A retrospective analysis was conducted on 17 cases of prostate cancer patients who received treatment with darolutamide in combination with ADT at our hospital from January to December 2022. The median age was 70 (range: 56 to 92) years old. The median pre-treatment prostate-specific antigen (PSA) level was 63.50 (range: 29.16 to 700.74) ng/ml. Sixteen cases had a Gleason score of 8 or above, and 11 cases were classified as high tumor burden (with four or more bone metastases and/or visceral metastases). The patients were treated with darolutamide in combination with goserelin (10.8 mg, subcutaneous injection, every 12 weeks). The decrease in PSA levels was observed at 2 weeks and at 1, 2, 3, and 6 months post-treatment. The time to achieve a 50% decrease in PSA level (PSA50), a 90% decrease (PSA90), and a PSA level of ≤0.2 ng/ml was recorded.Adverse drug reactions were also documented.Results:All the 17 patients were followed up and continued to receive darolutamide at our center without any loss to follow-up. The median follow-up time was 11.4(8.9, 15.3)months. It showed a median PSA decrease from baseline of 83.33% at 2 weeks, 95.37% at 1 month, 96.71% at 2 months, 97.22% at 3 months, and 99.10% at 6 months. The median time to achieve PSA50, PSA90, and PSA ≤ 0.2 ng/ml were 1.3 (0.9, 1.7)months, 1.7 (1.2, 2.4)months, and 3.6 (2.9, 4.5)months respectively. Six patients with bone metastases experienced relief of metastatic lesions after treatment. Only one patient developed papules on the left upper limb, which were assessed as grade 1 rash, and the rash disappeared after three days treatment of topical application of hydrocortisone cream.Conclusions:Darolutamide could rapidly control and significantly reduce PSA levels in prostate cancer patients, with a favorable safety profile.
5.Low-expression of ACOT4 Promotes the Damage and Crystals Formation of HK2 Cell by Calcium Oxalate
Shenghan WANG ; Zhentao LEI ; Yuqiang SHI
Journal of Medical Research 2024;53(6):113-118
Objective To investigate the effect of ACOT4 expression on the formation of calcium oxalate stones.Methods The HK2 cell of human tubular epithelial cells was used as subject,HK2 cell was treated with calcium oxalate,and the expression of ACOT4 was interfered with by siRNA.The gene expression levels in HK2 cell were detected by qPCR and Western blot.The cell viability was de-tected by CCK-8 assay.The cell apoptosis was detected by flow cytometry.The cell damage was detected by LDH assay.The adhesion ability of HK2 cell to calcium oxalate crystals was detected by crystal adhesion experiment.Results Calcium oxalate could regulate the expression of ACOT4 in HK2 cell.Interfering with ACOT4 can significantly inhibit the proliferation ability of HK2 cell,and promote the effect of cell activity reduction,damage and apoptosis of calcium oxalate to HK2 cell.At the same time,interfering with ACOT4 can sig-nificantly promote the adhesion ability of HK2 cells to calcium oxalate crystals.Conclusion Knocking down of ACOT4 can promote the damage of calcium oxalate to HK2 cell and promote the adhesion ability of HK2 cell to calcium oxalate crystals.
6.Value of number of negative lymph nodes in predicting the prognosis of patients with esophageal cancer after neoadjuvant therapy and the construction of nomogram prodiction model
Yueyang YANG ; Peng TANG ; Zhentao YU ; Haitong WANG ; Hongdian ZHANG ; Mingquan MA ; Yufeng QIAO ; Peng REN ; Xiangming LIU ; Lei GONG
Chinese Journal of Digestive Surgery 2023;22(3):371-382
Objective:To investigate the value of number of negative lymph nodes (NLNs) in predicting the prognosis of patients with esophageal cancer after neoadjuvant therapy and the construction of nomogram prodiction model.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 924 patients with esophageal cancer after neoadjuvant therapy uploaded to the Surveillance, Epidemiology, and End Results Database of the National Cancer Institute from 2004 to 2015 were collected. There were 1 624 males and 300 females, aged 63 (range, 23?85)years. All 1 924 patients were randomly divided into the training dataset of 1 348 cases and the validation dataset of 576 cases with a ratio of 7:3 based on random number method in the R software (3.6.2 version). The training dataset was used to constructed the nomogram predic-tion model, and the validation dataset was used to validate the performance of the nomogrram prediction model. The optimal cutoff values of number of NLNs and number of examined lymph nodes (ELNs) were 8, 14 and 10, 14, respectively, determined by the X-tile software (3.6.1 version), and then data of NLNs and ELNs were converted into classification variables. Observation indicators: (1) clinicopathological characteristics of patients in the training dataset and the validation dataset; (2) survival of patients in the training dataset and the validation dataset; (3) prognostic factors analysis of patients in the training dataset; (4) survival of patients in subgroup of the training dataset; (5) prognostic factors analysis in subgroup of the training dataset; (6) construction of nomogram prediction model and calibration curve. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curve and Log-Rank test was used for survival analysis. The COX proportional hazard model was used for univariate and multivariate analyses. Based on the results of multivariate analysis, the nomogram prediction model was constructed. The prediction efficacy of nomogram prediction model was evaluated using the area under curve (AUC) of the receiver operating characteristic curve and the Harrell′s c index. Errors of the nomogram prediction model in predicting survival of patients for the training dataset and the validation dataset were evaluated using the calibration curve. Results:(1) Clinicopathological characteristics of patients in the training dataset and the validation dataset. There was no significant difference in clinicopatholo-gical characteristics between the 1 348 patients of the training dataset and the 576 patients of the validation dataset ( P>0.05). (2) Survival of patients in the training dataset and the validation dataset. All 1 924 patients were followed up for 50(range, 3?140)months, with 3-year and 5-year cumulative survival rate as 59.4% and 49.5%, respectively. The 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 in the training dataset was 46.7%, 62.0% and 66.0%, respectively, and the 5-year cumulative survival rate was 38.1%, 52.1% and 59.7%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=33.70, P<0.05). The 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 in the validation dataset was 51.1%, 54.9% and 71.2%, respectively, and the 5-year cumulative survival rate was 39.3%, 42.5% and 55.7%, respectively. There was a significant difference in the survival of these patients in the validation dataset ( χ2=14.49, P<0.05). The 3-year cumulative survival rate of patients with number of ELNs as <10, 10?14 and >14 in the training dataset was 53.9%, 60.0% and 62.7%, respectively, and the 5-year cumulative survival rate was 44.7%, 49.1% and 56.9%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=9.88, P<0.05). The 3-year cumulative survival rate of patients with number of ELNs as <10, 10?14 and >14 in the validation dataset was 56.2%, 47.9% and 69.3%, respectively, and the 5-year cumula-tive survival rate was 44.9%, 38.4% and 51.9%, respectively. There was a significant difference in the survival of these patients in the validation dataset ( χ2=9.30, P<0.05). (3) Prognostic factors analysis of patients in the training dataset. Results of multivariate analysis showed that gender, neoadjuvant pathological (yp) T staging, ypN staging (stage N1, stage N2, stage N3) and number of NLNs (8?14, >14) were independent influencing factors for the prognosis of patients with esophageal cancer after neoadjuvant therapy ( hazard ratio=0.65, 1.44, 1.96, 2.41, 4.12, 0.69, 0.56, 95% confidence interval as 0.49?0.87, 1.17?1.78, 1.59?2.42, 1.84?3.14, 2.89?5.88, 0.56?0.86, 0.45?0.70, P<0.05). (4) Survival of patients in subgroup of the training dataset. Of the patients with NLNs in the training dataset, the 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 was 61.1%, 71.6% and 76.8%, respectively, and the 5-year cumulative survival rate was 50.7%, 59.9% and 70.1%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=12.66, P<0.05). Of the patients with positive lymph nodes in the training dataset, the 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 was 26.1%, 42.9% and 44.7%, respectively, and the 5-year cumulative survival rate was 20.0%, 36.5% and 39.3%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=20.39, P<0.05). (5) Prognostic factors analysis in subgroup of the training dataset. Results of multivariate analysis in patients with NLNs in the training dataset showed that gender, ypT staging and number of NLNs (>14) were independent influencing factors for the prognosis of patients with esophageal cancer after neoadju-vant therapy ( hazard ratio=0.67, 1.44, 0.56, 95% confidence interval as 0.47?0.96, 1.09?1.90, 0.41?0.77, P<0.05). Results of multi-variate analysis in patients with positive lymph nodes in the training dataset showed that race as others, histological grade as G2, ypN staging as stage N3 and number of NLNs (8?14, >14) were independent influencing factors for the prognosis of patients with esophageal cancer after neoadjuvant therapy ( hazard ratio=2.73, 0.70, 2.08, 0.63, 0.59, 95% confidence interval as 1.43?5.21, 0.54?0.91, 1.44?3.02, 0.46?0.87, 0.44?0.78, P<0.05). (6) Construction of nomogram prediction model and calibration curve. Based on the multivariate analysis of prognosis in patients of the training dataset ,the nomogram prediction model for the prognosis of patients with esophageal cancer after neoadju-vant treatment was constructed based on the indicators of gender, ypT staging, ypN staging and number of NLNs. The AUC of nomogram prediction model in predicting the 3-, 5-year cumulative survival rate of patients in the training dataset and the validation dataset was 0.70, 0. 70 and 0.71, 0.71, respectively. The Harrell′s c index of nomogram prediction model of patients in the training dataset and the validation dataset was 0.66 and 0.63, respectively. Results of calibration curve showed that the predicted value of the nomogram prediction model of patients in the training dataset and the validation dataset was in good agreement with the actual observed value. Conclusion:The number of NLNs is an independent influencing factor for the prognosis of esophageal cancer patients after neoadjuvant therapy, and the nomogram prediction model based on number of NLNs can predict the prognosis of esophageal cancer patients after neoadjuvant therapy.
7.Analysis of the clinical effect of single J tube of bilateral ureter through the bladder stoma to treat vesicovaginal fistula after radiotherapy of cervical cancer
Yuqiang SHI ; Shenghan WANG ; Zhentao LEI ; Lin YANG ; Qiang GAO ; Kaishuang WANG ; Bao ZHANG
Chinese Journal of Urology 2023;44(1):58-59
This article retrospectively analyzed the clinical data of 8 patients with vesicovaginal fistula after radiotherapy for cervical cancer admitted in our hospital from January 2015 to October 2021. All of them underwent cystostomy under local anesthesia. A single J tube of bilateral ureters was retained under cystoscope, and the single J tube was introduced into the fistula bag through the cystostomy opening. All patients wore diapers for a long time before operation, and used urine pads 0-2 pieces/day after operation. QOL score was 5.3±0.5 points before operation, and 2.5±0.5 points after operation. The patient's body odor basically disappeared. The vesicovaginal fistula can be repaired by surgery, but for patients who cannot be operated or failed repeatedly due to various reasons, a single J tube of bilateral ureters can be drawn out through the cystostomy opening, which can improve the quality of life of patients through minor trauma.
8.Progress of comprehensive surgical treatment for esophageal cancer
Zhentao YU ; Lei GONG ; Yueyang YANG ; Peng TANG
Chinese Journal of Digestive Surgery 2022;21(1):30-33
Esophageal cancer is one of the common malignant tumors in the worldwide and has regional characteristics in China. At present, the treatment of esophageal cancer is still a comprehensive diagnosis and treatment mode based on surgery. With the application of minimally invasive technique in surgery of esophageal cancer, the concept of surgical diagnosis and treatment for esophageal cancer is constantly updating. The application of robotic surgical system in esophageal surgery promotes the surgical quality of lymph node dissection and improves the technique of intraluminal anastomosis under total endoscopy. For locally advanced esophageal cancer, a diagnosis and treatment mode based on neoadjuvant therapy has been gradually accepted by most of doctors around China. Combined with the latest researches at home and abroad, the authors investigate the development of surgical techniques, the renewal of surgical concept and the changes on diagnosis and treatment, summarize the new advances in comprehensive surgical treatment for esophageal cancer, in order to provide the theoretical guidance for the standardized treatment of esophageal cancer.
9.Efficacy comparison of robot-assisted percutaneous screw implantation and free-hand open screw implantation by Wiltse approach in the treatment of thoracolumbar fracture
Shengyang DU ; Jun DAI ; Zhentao ZHOU ; Bingchen SHAN ; Xiaofeng LIU ; Peng ZHANG ; Yingzi ZHANG ; Fengxian JIANG ; Jinyu BAI ; Lei CAO ; Xiaozhong ZHOU
Chinese Journal of Trauma 2022;38(2):109-115
Objective:To compare the clinical efficacy of robot-assisted percutaneous screw implantation and free-hand open screw implantation by Wiltse approach in the treatment of thoracolumbar fracture.Methods:A retrospective cohort study was performed to analyze the clinical data of 71 patients with thoracolumbar fracture admitted to Second Affiliated Hospital of Soochow University from May 2018 to May 2020. There were 52 males and 19 females, with age range of 22-54 years[(41.0±7.8)years]. Of all, 33 patients were treated with robot-assisted percutaneous screw implantation (Group A) and 38 patients were treated with free-hand open screw implantation by Wiltse approach (Group B). Following parameters were measured, including frequency of radiation exposure, operation time, intraoperative blood loss, length of hospital stay, incidence of complications, rate of fracture healing at 3 months and 6 months postoperatively, visual analogue scale (VAS) and Oswestry dysfunction index (ODI) at 3 days, 3 months, 6 months postoperatively and at the last follow-up, anterior vertebral body height ratio and sagittal Cobb angle preoperatively, at 3 days postoperatively and at the last follow-up, and rate of screw implantation of grade A and B and rate of facet joint violation at 3 days postoperatively.Results:All patients were followed up for 10-24 months[(15.2±4.4)months]. Frequency of radiation exposure and operation time showed no statistical differences between the two groups (both P>0.05). Intraoperative blood loss was 100(100, 135)ml in Group A, less than 160(120, 200)ml in Group B ( P<0.01). Length of hospital stay was 8(7, 11) days in Group A, shorter than 12(10, 16)days in Group B ( P<0.01). There were no complications such as infection, spinal nerve injury or cerebrospinal fluid leakage in both group. There were no significant differences between the two groups in the rate of fracture healing at 3 and 6 months postoperatively (all P>0.05). VAS and ODI in Group A was 3(2, 4)points and 21(18, 23)points at 3 days postoperatively, lower than 4 (3, 5)points and 27(20, 32)points in Group B ( P<0.05 or 0.01), and the two groups showed no significant differences in VAS and ODI at other time points (all P>0.05). There were no significant difference in the anterior vertebral body height ratio or sagittal Cobb angle between the two groups at 3 days postoperatively and at the last follow-up (all P>0.05). Rate of screw implantation of grade A and B was 96.5% (191/198) in Group A, higher than 90.4% (206/228) in Group B ( P<0.05). Rate of facet joint violation was 4.0%(8/198) in Group A, lower than 11.8% (27/228) in Group B ( P<0.01). Conclusion:For thoracolumbar fracture, robot-assisted percutaneous screw implantation is superior to free-hand open screw implantation by Wiltse approach in terms of less bleeding, shorter hospitalization, earlier pain alleviation, higher accuracy of screw implantation and lower risk of facet joint violation.
10.Ezrin enhancer knockout inhibits the proliferation and migration of human esophageal carcinoma Eca-109 cells
LEI Yue ; YE Qingsong ; WEI Jinqi ; LI Wenna ; MO Zhentao ; ZHANG Qingfeng ; GAO Shuying
Chinese Journal of Cancer Biotherapy 2019;26(1):29-35
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Objective: To investigate the effects of ezrin enhancer knockout on ezrin gene expression, cell proliferation and migration of human esophageal carcinoma Eca-109 cells.
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Methods: The CRISPR/Cas9 recombinant plasmids targeting upstream/downstream of human ezrin enhancer were co-transfected into human esophageal carcinoma Eca-109 cells, and the cell line Eca-C2 with ezrin enhancer knockout was screened by purinomycin. Then the expression levels of ezrin mRNAand protein in Eca-C2 cells were detected by Real-time quantitative PCR (qPCR) and Western blotting, respectively; The expression levels of MAPK-pathway-related proteins were detected by protein array technology; and the effects of ezrin enhancer knockout on the proliferation and migration of Eca-C2 cells were analyzed by WST-1 method and wound-healing assay, respectively.
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Results:The human esophageal carcinoma cell line Eca-C2 with stable ezrin enhancer knockout was established successfully. Compared with control cells, the mRNA and protein expressions of ezrin in Eca-C2 cells were significantly reduced (all P<0.05).Among the 17 detected MAPK pathway related proteins in Eca-C2 cells, 9 proteins (AKT, CREB, GSK3b, MKK6, mTOR, P38, P53, P70S6K and RSK1) were down-regulated, and the cell proliferation and migration were significantly inhibited (all P<0.05).
Conclusion: ezrin enhancer knockout can significantly inhibit the cell proliferation and migration of human esophageal carcinoma Eca-109 cells.

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