1.Determination of non-steroidal anti-inflammatory drugs in the environmental water samples by a polyvinylimide-modified magnetic nanoparticles-based solid phase extraction coupled with high-performance liquid chromatography
Xiaohang TANG ; Huilin SONG ; Liying YAO ; Guowen QIN ; Xingchen WANG ; Wenyuan LIU ; Shunli JI
Journal of China Pharmaceutical University 2024;55(4):485-492
The long-term presence of non-steroidal anti-inflammatory drugs (NSAIDs) in the environmental water samples not only affects the life safety of aquatic organisms and disturbs the ecoenvironment, but also poses a serious threat to human health. In this study, amino-functionalized Fe3O4 nanoparticles (Fe3O4-NH2) were firstly prepared by solvothermal method. Subsequently, polyethyleneimine (PEI) with a branched chain structure was successfully grafted onto Fe3O4 nanoparticles by Schiff base reaction in aqueous solution at room temperature using glutaraldehyde as a cross-linking agent, and a recyclable PEI-grafted magnetic nano-sorbent (Fe3O4@PEI) was synthesized and applied for the detection of NSAIDs in the environmental water samples. The compositional properties of Fe3O4@PEI were investigated by different characterization methods and the parameters affecting the extraction of NSAIDs were optimized. Due to high adsorption of Fe3O4@PEI for NSAIDs, the quantitative analysis of four NSAIDs in the environmental water samples, ketoprofen, naproxen, diclofenac and tolfenamic acid, was performed in combination with high-performance liquid chromatography. A good linear relationship between the chromatographic peak area and concentration was observed in the range of 1−500 µg/mL. The recoveries of the samples at three different spiked levels ranged from 85.6% to 107.8%; the intra-day precision was less than 7.8% (n=6); and the inter-day precision was less than 9.5% (n=3). The method is simple, rapid, accurate and reliable, and can be used for the analysis of NSAIDs in the environmental water samples.
2.Clinical analysis of prostate targeted biopsy guided by multiparametric magnetic resonance imaging and 68Ga-PSMA PET/CT image fusion
Guowen LIN ; Bo DAI ; Dingwei YE ; Chang LIU ; Yao ZHU ; Xiaojian QIN ; Hongkai WANG
Chinese Journal of Urology 2022;43(7):484-489
Objective:To explore clinical value of prostate target biopsy guided by multiparametric magnetic resonance imaging (mpMRI) and 68Ga-labeled prostate specific membrane antigen ligand imaging positron emission tomography/X-ray computed tomography ( 68Ga-PSMA PET/CT) image fusion. Methods:The data of 50 patients admitted to Fudan University Shanghai Cancer Center from January 2021 to February 2022 who underwent mpMRI and 68Ga-PSMA PET/CT to guide prostate biopsy were retrospectively analyzed. The median age was 70 (63-79) years, the median serum tPSA value was 8.1 (6.8-83.0) ng/ml, and the prostate volume was 45.5 (30-80) ml. 36 cases were positive by mpMRI, including PI-RADS score 3 in 5 cases, 4 score in 19 cases, 5 score in 12 cases. 32 cases were positive by 68Ga-PSMA PET/CT examination, of which 30 cases were double positive and the fusion of both imaging techniques was positive, referred to as PET/CT-MRI. The patient's mpMRI and 68Ga-PSMA PET/CT images were imported into the MIM fusion software, and the outline of the prostate and the target area were outlined respectively. When PET/CT and MRI double positive cases were biopsied, the two images were alternately fused, calibrated and locked with the real-time prostate ultrasound interface(PET/CT-MRI). Single-positive cases were guided by positive images to complete targeted biopsy, and 12-needle systematic biopsies were completed after targeted biopsy and double-negative cases. The advantages of targeted biopsy and systematic biopsy was evaluated, and the diagnostic performance (sensitivity, specificity, positive predictive value, and negative predictive value) was analyzed. Results:Among the 50 biopsy patients in this group, 31 (62%) had prostate cancer, of which 22 (44%) were CsPCa. There was no significant difference in the detection rate of prostate cancer between targeted biopsy and systematic biopsy [78.9% (30/38) and 62.0% (31/50), P=0.088], and there was no significant difference in the detection rate of CsPCa [57.9% (22/38) and 40.0% (20/50), P=0.096]. The positive rate of the biopsy needles number was significantly different [86.3% (69/80) and 19.0% (114/ 600), P<0.001]. The detection rates of prostate cancer in mpMRI positive, PET/CT positive and PET/CT-MRI positive cases were 83.3% (30/36), 90.6% (29/32) and 96.6% (29/30) respectively, the detection rates of CsPCa were 61.1% (22/36), 68.8% (22/32) and 73.3% (22/30) respectively.The sensitivity, specificity, positive predictive value and negative predictive value of mpMRI in the diagnosis of prostate cancer were 96.8%(30/31), 68.4%(13/19), 83.3%(30/36)and 92.9%(13/14), respectively.Those values in 68Ga-PSMA PET/CT were 93.5%(29/31), 84.2%(16/19), 90.6%(29/32)and 88.9%(16/18), respectively.Those values in PET/CT-MRI were 93.8%(29/31), 94.7%(18/19), 96.7%(29/30)and 90.0%(18/20), respectively. The above four indicators of mpMRI diagnosis of CsPCa were 100.0%(22/22), 50.0%(14/28), 61.1%(22/36)and 100.0%(14/14), respectively.Those indicators in 68Ga-PSMA PET/CT were 100.0%(22/22), 64.3%(18/28), 68.8%(22/32)and 100.0%(18/18), respectively.Those indicators in PET/CT-MRI was 100.0%(22/22), 71.4%(20/28), 73.2%(22/30)and 100.0%(20/20), respectively. The detection efficiency of PET/CT-MRI was better than that of mpMRI (Kappa value was 0.737, P=0.031). Conclusions:PET/CT-MRI image fusion-guided targeted prostate biopsy can effectively improve the detection efficiency of prostate cancer and clinically significant prostate cancer, and increase the positive rate.
3.Efficacy and safety of radium-223 in 48 patients with bone metastatic castration resistant prostate cancer
Hongkai WANG ; Bo DAI ; Yao ZHU ; Xiaojian QIN ; Guowen LIN ; Beihe WANG ; Junlong WU ; Dingwei YE
Chinese Journal of Urology 2022;43(7):535-539
Objective:To observe the efficacy and safety of radium-223 in metastatic castration resistant prostate cancer (mCRPC) with bone metastasis.Methods:The clinical data of 48 patients with mCRPC treated with radium-223(55 kBq/kg, once every 4 weeks, planned to use for 6 cycles)from February 2021 to May 2022 were analyzed retrospectively. All patients had symptomatic bone metastasis without visceral metastasis, which the number of bone metastasis was more than one site.They were all classified as IVb stage. The average age was 70.5 (ranging 49-90) years. The median PSA was 44.70(ranging 0.15-1 864.00) ng/ml. The median ALP was 162 (ranging 43-1 589) U/L. The median time from mCRPC diagnosis to radium-223 use was 10 (ranging 3-47) months. 9, 18 and 11 patients had received first-line, second-line and third-line treatment for mCRPC before enrollment respectively, 10 patients had received at least fourth-line treatment. 38 (79.1%), 31 (64.5%), 30 (62.5%) and 7 (14.6%) patients had used abiraterone, enzalutamide, docetaxel and olaparib before enrollment. The probability of PSA level decrease >30%, ALP level decrease >30%, symptom improvement rate, median overall survival (OS), as well as the occurrence of treatment-related adverse reactions and the reasons for withdraw treatment were analyzed.Results:The median follow-up time was 8 (ranging 1-16) months. 11 patients completed all 6 courses of treatment. The median number of completed courses was 4 (ranging 1-6). 27 patients (56.2%) received radium-223 and bone protection drugs (Bisphosphate/ Denosumab). PSA decreased by >30% was recorded in 10 patients (20.8%) and ALP decreased by >30% was recorded in 25 patients (52.1%). 23 cases (47.9%) reported bone pain relief during treatment. Among the 9 patients who had received first-line of mCRPC previously, 6 cases (66%) had relief of bone pain symptoms, and 4 cases (44%) had a decrease of PSA >30%. Among the 18 patients who had previously received second-line mCRPC treatment, 11 cases (61%) had relief of bone pain symptoms, and 4 cases (22%) had a decrease of PSA >30%. Among the 21 patients who had received third-line or more mCRPC treatment in the past, 6 (28.5%) had symptom relief, and 2 (9.5%) had PSA decrease >30%. The median overall survival (OS) was not reached, and the OS was estimated to be 12.5 months using the Kaplan-Meier method. The most common hematological adverse effects were thrombocytopenia (15 cases, 31.2%; grade 3 in 6 cases and grade 4 in 0), followed by leucopenia (11 cases, 22.9%; grade 3 in 4 cases and grade 4 in 1 case) and anemia (8 cases, 16.7%; grade 3 in 3 cases and grade 4 in 0). Non-hematological adverse reactions included fever in 1 case (2.1%), constipation in 4 cases (8.3%), nausea and vomiting in 10 cases (20.8%), diarrhea in 7 cases (14.6%), dizziness in 1 case (2.1%) and fatigue in 11 cases (22.9%). Seven cases were discontinued due to intolerable adverse reactions (median 2 courses), 14 cases were discontinued due to disease progression or death (median 2 courses), and 5 cases were discontinued due to other reasons (median 1 course).Conclusions:Radium-223 has a good performance in symptom control for mCRPC patients who have previously received first-line or second-line therapy. Due to the high incidence of hematological adverse reactions, more attention should be paid to the changes of hemogram during the treatment, and timely treatment should be carried out to improve the drug tolerance of patients.
4.Clinical analysis of cryotherapy in patients with primary tumor recurrence after radical radiotherapy for prostate cancer
Guowen LIN ; Bo DAI ; Dingwei YE ; Yao ZHU ; Xiaojian QIN ; Hongkai WANG
Chinese Journal of Urology 2021;42(9):662-665
Objective:To explore the clinical value of cryoablation technology in the treatment of patients with primary tumor recurrence after radical radiotherapy for prostate cancer.Methods:The clinical data of 21 patients with prostate cancer recurrence after radical radiotherapy in the Fudan University Affiliated Cancer Hospital from August 2017 to February 2021 was retrospectively analyzed. The average age was 73.1 (57.3-85.0) years old, and the Gleason score was 6 in 5 cases, 7 in 8 cases, and ≥8 in 8 cases. The clinical stage of the first diagnosis: 13 cases of cT 2 stage; 8 cases of cT 3 stage. The baseline PSA before radiotherapy was 35.3 (6.4-78.5) ng/ml, and the lowest PSA after radiotherapy was 1.8 ng/ml. After a median follow-up of 8 (3-12) months, all patients were detected with persistently elevated PSA. Pelvic MRI and PSMA SPECT showed that the primary prostate lesion had recurred. PSA before cryoablation was 4.1 (1.8-14.4) ng/ml. Comprehensive assessment of preoperative examination showed that the patient only had a recurrence of the primary tumor, and no lymph node or distant metastasis was seen. An argon-helium cryogenic surgical treatment system was used to place 1 to 3 cryo-needles for recurring lesions, and cryoablation was performed using two cold and hot cycles. Observation indicators include prognostic indicators such as PSA, recurrence and metastasis, and the occurrence of adverse reactions. Results:Complications after cryoablation include: 2 cases of urinary retention, 1 case of urinary tract infection, and 2 cases of urination with tissue shedding. The PSA of 11 cases decreased rapidly 2 to 3 months after operation, and dropped to the lowest median value of 0.4 (0.003 to 2.8) ng/ml. After cryoablation, the median follow-up was 18 (6-51) months. Imaging examinations in 1 case showed that the prostate still had limited diffusion or increased PSMA uptake, and 4 cases had PSA progression but no recurrence or metastasis. The median recurrence time for advanced patients was 13 (4-36) months. Larger prostate volume ( P<0.001) and higher blood PSA before ablation( P=0.021) were related to biochemical recurrence. Conclusions:Prostate cryoablation could delay the progression of the primary tumor after radical radiotherapy for prostate cancer. The incidence of complications such as urinary retention and urinary tract infection is not high, and it is generally safe and controllable.
5.Application of regional lymph node dissection in patients with metastatic castration resistant prostate cancer
Hongkai WANG ; Bo DAI ; Yao ZHU ; Guowen LIN ; Xiaojian QIN ; Dingwei YE
Chinese Journal of Urology 2021;42(9):670-674
Objective:To observe the clinical effect and safety of regional lymph node dissection in metastatic castration resistant prostate cancer(mCRPC).Methods:The clinical data of 22 patients with mCRPC who underwent regional lymph node dissection in our hospital from August 2015 to May 2021 were retrospectively analyzed. All patients had undergone radical prostatectomy and entered mCRPC, metastatic lymph nodes limited to pelvic or retroperitoneal without other metastasis were determined by PSMA-PET in 5 cases and PSMA-SPECT in 17 cases. The median time from radical surgery to mCRPC was 32 (4-96) months, and the median time from discovery of mCRPC to regional lymph node dissection was 4 (1-43) months. The median PSA before regional lymph node dissection was 4.44 (2.00-22.15) ng/ml. Image of local examination showed pelvic lymph node metastasis in 16 cases, retroperitoneal lymph node metastasis in 3 cases, pelvic together with retroperitoneal lymph node metastasis in 3 cases. Before regional lymph node dissection, 18 patients were treated with drug castration combined with first-generation antiandrogens, and 4 patients were treated with drug castration combined with abiraterone. The lymph node dissection range was determined according to the location of metastatic lymph nodes. Obturator lymph nodes and lymph node metastasis around external iliac and internal iliac vessels: the range of dissection includes fibrous adipose tissue around external iliac vein and internal iliac vein, and obturator lymph adipose tissue. Common iliac and pelvic floor lymph node metastasis: dissect lymphoid adipose tissue around common iliac vessels on the basis of the original dissection range as far as the aortic bifurcation. Retroperitoneal lymph node metastasis: remove all lymph node adipose tissue located between the bifurcation of renal artery and aorta. The PSA remission rate, PSA remission time, surgical complications and other relevant clinicopathological features were analyzed.Results:Among the 22 cases, 6 cases underwent unilateral pelvic lymph node dissection, 10 cases underwent bilateral pelvic lymph node dissection, 3 cases underwent retroperitoneal lymph node dissection, and 3 cases underwent pelvic and retroperitoneal lymph node dissection at the same time. 19 cases (86.3%) showed positive lymph nodes by pathology. An average of 9.8 (3-29) lymph nodes were dissected in each patient, with an average of 4.1 (0-12) positive lymph nodes. All 22 cases continued to use the previous anti-androgen therapy after lymph node dissection. 17 cases (77.3%) achieved PSA remission after operation, of which 9 cases developed PSA progression, and the median PSA progression time was 12 (2-36) months. Univariate analysis showed that PSA value during radical operation ( P=0.029), N stage during radical operation ( P=0.057), the number of positive lymph nodes during regional lymph node dissection ( P=0.069) and the location of lymph node metastasis during regional lymph node dissection ( P =0.005) were related to the progression time of PSA. Postoperative complications: lymphatic leakage in 7 cases; 5 cases of postoperative fever, of which 1 case was confirmed to have pelvic bacterial infection. One patient suffered from massive intra-operative bleeding due to the invasion of blood vessels by metastatic lymph nodes. After timely hemostasis during the operation, the patient returned to the ward and was discharged 6 days later. One case of intestinal obstruction, and 1 case of body surface wound infection. 6 cases of lymphatic leakage healed within 1 month after operation, and 1 case of lymphatic leakage healed within 3 months after operation. Conclusions:For mCRPC patients with lymph node metastasis which could be surgically removed, regional lymph node dissection may further delay the starting time of posterior drugs, and the complications are relatively controllable.
6.Comprehensive treatment of metastatic hormone sensitive prostate cancer: a case report and literature review
Guowen LIN ; Bo DAI ; Dingwei YE ; Yao ZHU ; Xiaojian QIN ; Hongkai WANG
Chinese Journal of Urology 2021;42(Z1):54-58
Retrospectively analyze the clinicopathological data of a patient with metastatic hormone sensitive prostate cancer, and review relevant literature. The patient was male, 68 years old. Complaints of dysuria and urgency for half a year. Blood PSA>100 ng/ml, magnetic resonance showed that the prostate was occupying space, the boundary with the seminal vesicle gland was not clear, and the pelvic cavity had multiple bone lesions. Bone scan revealed multiple bone metastases. The prostate biopsy showed adenocarcinoma, Gleason score 5+ 5. The clinical stage was T 3N 0M 1b.A palliative transurethral resection of the prostate was performed due to urination obstruction, and endocrine therapy with medical castration combined with abiraterone and prednisone. PSA was continuously controlled at <0.006 ng/ml. After half a year of treatment, the prostate-specific membrane antigen single-photon emission computerized tomography and magnetic resonance examination revealed sternal and parasternal soft tissue lesions. Local radiotherapy and continuous endocrine therapy were given. The disease was under long-term control.There are various treatment options for metastatic hormone sensitive prostate cancer. Medical castration treatment combined with abiraterone and prednisone can effectively control the disease with mild adverse reactions. Palliative transurethral resection of the prostate can improve the symptoms of urinary obstruction and may also improve the prognosis of patients.
7. Chemotherapy combined with androgen-deprivation therapy in high-volume metastatic hormone sensitive prostate cancer: a short-term efficacy and safety analysis
Peihang XU ; Yijun SHEN ; Wenjun XIAO ; Guowen LIN ; Xiaojian QIN ; Yao ZHU ; Bo DAI ; Dingwei YE
Chinese Journal of Surgery 2019;57(6):418-421
Objective:
To investigate the short-term efficacy and adverse events of chemotherapy combined with androgen-deprivation therapy in high-volume metastatic hormone sensitive prostate cancer.
Methods:
From March 2015 to August 2017, 55 patients with high-volume metastatic hormone sensitive prostate cancer were enrolled at Department of Urology, Fudan University Shanghai Cancer Center receiving chemotherapy combined with androgen-deprivation therapy. The age was 65(8) years (
8.Observation of preliminary clinical effect and analysis of perioperative complications of radical prostatectomy for patients with oligometastatic prostate cancer
Gaoxiang LI ; Bo DAI ; Dingwei YE ; Yao ZHU ; Hualei GAN ; Guowen LIN ; Xiaojian QIN ; Wenjun XIAO ; Chengyuan GU
China Oncology 2017;27(1):20-25
Background and purpose:It has been demonstrated that radical prostatectomy for patients with oligometastatic prostate cancer may contribute to improving local control of prostate cancer and overall survival by several retrospective studies. Perioperative complications play an important role in determining whether radical prostatectomy is appropriate for patients with oligometastatic prostate cancer. This study aimed to discuss the recurrence rate and the sever-ity of perioperative complications, and the primary curative effect of radical prostatectomy on oligometastatic prostate can-cer patients.Methods:A total number of 247 patients who received radical prostatectomy were recruited in the study from Jul. 2015 to Jan. 2016, including 25 patients with oligometastatic prostate cancer and 222 patients with localized prostate cancer. Patients with perioperative complications in both groups were graded with the Clavien-Dindo grading system. The proportion of PSA decline and the rates and severity of perioperative complications were analyzed in both groups.Results:The cases of prostate specific antigen (PSA) decline in the oligometastatic group were 21 (84.0%), lower than the localized group with 212 cases (95.5%). There were 6 cases (24.0%) with postoperative complications in the oligometastatic group, including serious complications (Ⅲ or above) 1 case (4.0%), and 49 cases (22.1%) with postoperative complications in the localized group, including serious complications (Ⅲ or above) 7 cases (3.2%). The differences between the groups reached no statistical significance (P>0.05).Conclusion:Radical prostatectomy for patients with oligometastatic prostate cancer could be safe, effective, and appropriate, the risk of perioperative complications should not be one of the limiting factors.
9.Biomeasurement and analysis of the anterior chamber angle and related tissues in myopia eyes
Xinmin, LIU ; Sizhen, LI ; Dabo, WANG ; Guowen, ZHANG ; Huiqian, JI ; Jianmin, QIN
Chinese Journal of Experimental Ophthalmology 2015;33(6):525-530
Background Myopia is one of the main blinding diseases worldwide.At present,a lot of studies on ocular structure focus on the changes of corneal curvature(CC),central corneal thickness (CCT),anterior chamber depth (ACD),ocular axial length (AL) and choroid and retina,but the research of anterior chamber angle section structure form and ciliary body shape is lack.Objective This study was to measure and analyze the changes of the anterior chamber angle and related tissue structure in myopic eyes.Methods One hundred and forty-nine eyes of 149 subjects were included from May 2008 to May 2010 in Eighth Hospital of Qingdao City with the ages of 18-40years old under the informed consent.The subjects were assigned to the emmetropia group (30 eyes) ([0.02±0.18] D),low myopia group(46 eyes) ([-1.64±0.69] D),moderate myopia group (35 eyes) ([-4.56±0.66] D) and high myopia group (38 eyes) ([-7.04 ± 1.02] D).Conventional indexes including intraocular pressure (IOP),CCT,CC,AL and ACD were measured,and the indexes including chamber angel open distance (AOD),iris thickness (IT1,IT2,IT3),the position of ciliary body such as A-angel,B-angel,trabecular ciliary process distance (TCPD),irisciliary process distance (ICPD) and ciliary body thickness (CBT1,CBT2,CBT3) were measured by ultrasound biomicroscope(UBM).Results The IOP,CC and CCT values showed slight change in different groups without remarkable difference among them (all at P>0.05).As the increase of myopic degree,AL was extended and ACD was deepened,showing significant differences among the groups (both at P<0.05).There were no significant differences in IT1,IT2 and IT3 among the four groups (all at P>0.05).However,the measuring values of angle opening degree (TIA and AOD500),ciliary position (A-angle,B-angle,TCPD,ICPD) and CBT (CBT1,CBT2,CBT3) elevated with the increase of myopic degree (all at P<0.05).Positive correlations were found between AOD500 and ACD,A-angle,CBT1,CBT2,AL,negative correlations was found between AOD500 and myopic degree (r =0.573,0.513,0.325,0.398,0.542,-0.435,all at P<0.01);Positive correlations were found between TIA and ACD,A-angle,CBT1,CBT2,AL,negative correlations was found between AOD500 and myopic degree (r =0.573,0.464,0.276,0.410,0.539,-0.435,all at P < 0.01).Conclusions Within certain limits,as the increase of myopic degree,ACD deepens,the anterior chamber angle widens,ciliary process thickens and ciliary body backward shifts.
10.Validation of the MSKCC score model in advanced renal cell carcinoma patients treated with VEGF-targeted agents in China
Yaping HONG ; Yao ZHU ; Xudong YAO ; Shilin ZHANG ; Bo DAI ; Hailiang ZHANG ; Yijun SHEN ; Yiping ZHU ; Chunguang MA ; Wenjun XIAO ; Xiaojian QIN ; Guowen LIN ; Dingwei YE
Chinese Journal of Urology 2013;(2):143-146
Objective To validate the Memorial Sloan-Kettering Cancer Center(MSKCC)score model and evaluate the clinical efficacy of vascular endothelial growth factor(VEGF)-targeted agents in the treatment of advanced renal cell carcinoma(RCC)in China.Methods Three hundred and forty-five patients with advanced RCC and average age of 57(17-90)years were treated with VEGF-targeted agents.There were 306 cases of clear cell RCC,20 cases of papillary RCC,4 cases of chromophobe RCC,5 cases of renal collecting duct carcinoma,3 cases of medullary carcinoma and 7 cases of unclassified RCC.The main metastatic lesions were located at lung,bone and lymph nodes.Of them,205 cases were given the treatment of sorafenib 400 mg bid without off treatment,while 140 cases received sunitinib treatment in repeated six week cycles consisting of four weeks of sunitinib 50 mg daily followed by two weeks off treatment.Overall survival(OS)was estimated by the Kaplan-Meier method.Log-rank test and Harrell concordance index analysis were used to validate the MSKCC score model.Results The median follow-up period were 23(1-68)months in the whole group.The OS was 33 months,and survival rates at 1,2,3 year were 77.6%,59.3%,46.6%,respectively.According to the MSKCC score model,the patients were segregated into three risk categories: the favorable-risk group(no prognostic factors;n =169;49.0%),in which median OS(mOS)was 46 months and 2 year OS was 75.8%;the imtermediate-risk group(one or two prognostic factors;n =150;43.5%),in which mOS was 24 months and 2 year OS was 47.7%;and the poorrisk group(three to five prognostic factors;n =26;7.5%),in which mOS was 8 months and 2 year OS was 10.1%(log-rank P < 0.01).The concordance index was 0.687.Conclusions VEGF-targeted agents are effective in Chinese advanced RCC patients.The MSKCC score model can be incorporated into judging individualizing tumor prognosis and communicating about the treatment options with patients who are using VEGF-targeted agents.

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