1.HNRNPA1 gene is highly expressed in colorectal cancer:its prognostic implications and potential as a therapeutic target
Kai JI ; Guanyu YU ; Leqi ZHOU ; Tianshuai ZHANG ; Qianlong LING ; Wenjiang MAN ; Bing ZHU ; Wei ZHANG
Journal of Southern Medical University 2024;44(9):1685-1695
Objective To investigate the expression level of HNRNP A1 in colorectal cancer(CRC)and its prognostic implications.Methods We investigated HNRNP A1 expression level in CRC using HPA,TIMER,and GEPIA databases and analyzed its association with Ki-67 and VEGFA expressions.Kaplan-Meier Plotter database was used to analyze the correlation of HNRNP A1 mRNA levels with the survival rates of CRC patients.Pathway enrichment analysis was performed for predicting the biological roles of HNRNP A1 in CRC progression.Immunohistochemistry and Western blotting were used to examine the protein levels of HNRNP A1 in CRC versus adjacent tissues,and TIMER was used for assessing its expression in the infiltrating immune cells.In RKO/Caco2 cells,the effects of lentivirus-mediated knockdown of HNRNP A1 on cell proliferation and migration were observed,and the inhibitory effect of VPC-80051(a HNRNP A1 inhibitor)on cell proliferation was evaluated to assess its potential as a therapeutic agent.Results HNRNP A1 was significantly overexpressed in CRC tissues and correlated with a poor prognosis of the patients.HNRNP A1 expression level was correlated with the infiltrating immune cells in CRC microenvironment and positively correlated with MKI67 and VEGFA expressions in CRC.A high HNRNP A1 expression predicted a in survival and progression-free survival of CRC patients and was involved in multiple biological processes related with CRC progression.In RKO/Caco2 cells,HNRNP A1 knockdown significantly suppressed cell proliferation and migration,and treatment with VPC-80051 also effectively inhibited CRC cell proliferation.Immunohistochemical study demonstrated a close correlation of HNRNP A1 overexpression with tumor stage of CRC.Conclusion HNRNP A1 is overexpressed in CRC tissues to modulate cell proliferation and migration and is correlated with a poorer prognosis.VPC-80051 can effectively inhibit CRC cell proliferation,suggesting the potential of HNRNP A1 as a therapeutic target for CRC.
2.Long-term outcome of patients with rectal cancer who achieve complete or near complete clinical responses after neoadjuvant therapy: a multicenter registry study of data from the Chinese Watch and Wait Database
Yiming ZHAO ; Weihu WANG ; Wei ZHANG ; Lin WANG ; Shuai LI ; Jingwen WANG ; Leen LIAO ; Guanyu YU ; Zhen SUN ; Yanli QU ; Yang GONG ; Yun LU ; Tao WU ; Yunfeng LI ; Quan WANG ; Guohua ZHAO ; Yi XIAO ; Peirong DING ; Zhen ZHANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2024;27(4):372-382
Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.
3.Bowel preparation before colorectal surgery
Ning WANG ; Guanyu YU ; Wei ZHANG
Chinese Journal of Gastrointestinal Surgery 2024;27(6):642-645
High quality bowel preparation is a necessary part of preoperative preparation for colorectal surgery and one of the keys to the success of surgery, which directly affects the quality of intraoperative procedures and postoperative recovery of patients. Conventional intestinal preparation mainly includes three aspects: preoperative dietary control, intestinal cleansing and prophylactic use of antibiotics. With the development of evidence-based medicine, the concepts and methods of bowel preparation have also changed. Long fasting is no longer advocated before surgery, and the traditional mechanical bowel preparation are also challenged. This article summarizes the application and research progress of different intestinal preparation methods before colorectal surgery, aiming to provide reference for clinical work of colorectal surgeons.
4.Long-term outcome of patients with rectal cancer who achieve complete or near complete clinical responses after neoadjuvant therapy: a multicenter registry study of data from the Chinese Watch and Wait Database
Yiming ZHAO ; Weihu WANG ; Wei ZHANG ; Lin WANG ; Shuai LI ; Jingwen WANG ; Leen LIAO ; Guanyu YU ; Zhen SUN ; Yanli QU ; Yang GONG ; Yun LU ; Tao WU ; Yunfeng LI ; Quan WANG ; Guohua ZHAO ; Yi XIAO ; Peirong DING ; Zhen ZHANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2024;27(4):372-382
Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.
5.Bowel preparation before colorectal surgery
Ning WANG ; Guanyu YU ; Wei ZHANG
Chinese Journal of Gastrointestinal Surgery 2024;27(6):642-645
High quality bowel preparation is a necessary part of preoperative preparation for colorectal surgery and one of the keys to the success of surgery, which directly affects the quality of intraoperative procedures and postoperative recovery of patients. Conventional intestinal preparation mainly includes three aspects: preoperative dietary control, intestinal cleansing and prophylactic use of antibiotics. With the development of evidence-based medicine, the concepts and methods of bowel preparation have also changed. Long fasting is no longer advocated before surgery, and the traditional mechanical bowel preparation are also challenged. This article summarizes the application and research progress of different intestinal preparation methods before colorectal surgery, aiming to provide reference for clinical work of colorectal surgeons.
6.HNRNPA1 gene is highly expressed in colorectal cancer:its prognostic implications and potential as a therapeutic target
Kai JI ; Guanyu YU ; Leqi ZHOU ; Tianshuai ZHANG ; Qianlong LING ; Wenjiang MAN ; Bing ZHU ; Wei ZHANG
Journal of Southern Medical University 2024;44(9):1685-1695
Objective To investigate the expression level of HNRNP A1 in colorectal cancer(CRC)and its prognostic implications.Methods We investigated HNRNP A1 expression level in CRC using HPA,TIMER,and GEPIA databases and analyzed its association with Ki-67 and VEGFA expressions.Kaplan-Meier Plotter database was used to analyze the correlation of HNRNP A1 mRNA levels with the survival rates of CRC patients.Pathway enrichment analysis was performed for predicting the biological roles of HNRNP A1 in CRC progression.Immunohistochemistry and Western blotting were used to examine the protein levels of HNRNP A1 in CRC versus adjacent tissues,and TIMER was used for assessing its expression in the infiltrating immune cells.In RKO/Caco2 cells,the effects of lentivirus-mediated knockdown of HNRNP A1 on cell proliferation and migration were observed,and the inhibitory effect of VPC-80051(a HNRNP A1 inhibitor)on cell proliferation was evaluated to assess its potential as a therapeutic agent.Results HNRNP A1 was significantly overexpressed in CRC tissues and correlated with a poor prognosis of the patients.HNRNP A1 expression level was correlated with the infiltrating immune cells in CRC microenvironment and positively correlated with MKI67 and VEGFA expressions in CRC.A high HNRNP A1 expression predicted a in survival and progression-free survival of CRC patients and was involved in multiple biological processes related with CRC progression.In RKO/Caco2 cells,HNRNP A1 knockdown significantly suppressed cell proliferation and migration,and treatment with VPC-80051 also effectively inhibited CRC cell proliferation.Immunohistochemical study demonstrated a close correlation of HNRNP A1 overexpression with tumor stage of CRC.Conclusion HNRNP A1 is overexpressed in CRC tissues to modulate cell proliferation and migration and is correlated with a poorer prognosis.VPC-80051 can effectively inhibit CRC cell proliferation,suggesting the potential of HNRNP A1 as a therapeutic target for CRC.
7.Current status and prospect of CAR-T cell immunotherapy for colorectal cancer
Tianshuai ZHANG ; Leqi ZHOU ; Guanyu YU ; Wei ZHANG
Journal of Surgery Concepts & Practice 2023;28(5):483-487
Chimeric antigen receptor T(CAR-T)cell therapy is a new method of immunotherapy for cancer that has achieved remarkable results in treating blood tumors.However,colorectal cancer(CRC),as a solid tumor,has different characteristics from hematological tumors,which impose certain constraints on the selection of its therapeutic targets and the effectiveness of treatment of CAR-T therapy.Therefore,it is necessary to select therapeutic targets with high specificity and effectiveness according to the characteristics of CRC,as well as to break through the constraints such as adverse effects caused by the treatment and the solid tumor microenvironment,to make CAR-T therapy applicable in the treatment of CRC.This article aimed to summarize the strategy of selecting therapeutic targets for CAR-T cell immunotherapy for CRC,analyze the restrictive factors of this therapy in the treatment of CRC,and forecast the prospect of CAR-T cell immunotherapy for CRC.
8.Clinical efficacy and prognosis of simultaneous resection of synchronous colorectal liver metastasis in patients admitted in different phases
Rongbo WEN ; Leqi ZHOU ; Hao FAN ; Guanyu YU ; Gang LI ; Haifeng GONG ; Xiaoming ZHU ; Hao WANG ; Zheng LOU ; Enda YU ; Hantao WANG ; Lianjie LIU ; Xianhua GAO ; Liqiang HAO ; Ronggui MENG ; Wei ZHANG
Chinese Journal of Digestive Surgery 2022;21(6):788-795
Objective:To investigate the clinical efficacy and prognosis of simultaneous resection of synchronous colorectal liver metastasis in patients admitted in different phases.Methods:The retrospective cohort study was conducted. The clinicopathological data of 346 patients who underwent simultaneous resection of synchronous colorectal liver metastasis in the First Affiliated Hospital of Naval Medical University (Changhai Hospital of Shanghai) from January 2000 to April 2021 were collected. There were 217 males and 129 females, aged (58±12)years. Patients under-went simultaneous resection of synchronous colorectal liver metastasis. Observation indicators: (1) clinicopathological features of patients with synchronous colorectal liver metastasis in 2000?2010 and 2011?2021; (2) surgical and postoperative situations of patients with synchronous colorectal liver metastasis in 2000?2010 and 2011?2021; (3) analysis of prognosis of patients with synchro-nous colorectal liver metastasis in 2000?2010 and 2011?2021. Follow-up was conducted using telephone interview or outpatient examination to detect survival of patients. The follow-up was performed once every 3 months, including blood routine test, liver and kidney function test, car-cinoembryonic antigen (CEA) test, CA19-9 test, abdominal B-ultrasound examination, and once every 6 months, including chest computed tomography (CT) plain scan, liver magnetic resonance imaging (MRI) and/or CT enhanced scan, abdominal or pelvic MRI and/or CT enhanced scan, within postoperative 2 year. The follow-up was performed once every 6?12 months within postoperative 2?5 years including above reexaminations. Electronic colonoscopy was performed once a year after operation. The follow-up was up to November 12, 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distuibution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. Kaplan-Meier method was used to calculate survival rates and draw survival curves, and Log-Rank test was used to conduct survival analysis. Results:(1) Clinicopathological features of patients with synchronous colorectal liver metastasis in 2000?2010 and 2011?2021. Of the 346 patients, 59 cases underwent simultaneous resection within 2000?2010 and 287 cases underwent simultaneous resection within 2011?2021. The gender (males and females), cases with or without fundamental diseases, cases with the number of lymph nodes harvested in primary lesion as <12 or ≥12, the tumor diameter of primary lesion, the tumor diameter of liver metastasis lesion, the number of liver metastasis lesions, cases with or without preoperative treatment, cases with or without postoperative treatment, cases with adjuvant therapy as perioperative treatment, surgery or other treatment were 47, 12, 36, 23, 19, 40, (5.5±2.4)cm, (2.1±0.7)cm, 1.6±0.5, 59, 0, 16, 16, 0, 16, 43 in patients admitted in 2000?2010, respectively. The above indicators in patients admitted in 2011?2021 were 170, 117, 121, 166, 58, 229, (4.2±2.0)cm, (3.0±2.0)cm, 1.9±1.4, 208, 79, 34, 235, 74, 29, 184, respectively. There were significant differences in the above indicators between patients admitted in 2000?2010 and 2011?2021 ( χ2=8.73, 7.02, 4.07, t= 4.40, ?6.04, ?3.10, χ2=21.05, 28.82, 26.68, P<0.05). (2) Surgical and postoperative situations of patients with synchronous colorectal liver metastasis in 2000?2010 and 2011?2021. Cases with surgical methods as complete open surgery or laparoscopy combined with open surgery, the operation time, time to postoperative initial liquid food intake, cases with or without postoperative complications, cases with postoperative duration of hospital stay as ≤10 days or >10 days were 58, 1, (281±57)minutes, (5±1)days, 33, 26, 14, 45 in patients admitted in 2000?2010, respec-tively. The above indicators in patients admitted in 2011?2021 were 140, 147, (261±82)minutes, (3±1)days, 233, 54, 198, 89, respectively. There were significant differences in the above indicators between patients admitted in 2000?2010 and 2011?2021 ( χ2=49.04, t=2.24, 7.53, χ2=17.56, 26.02, P<0.05). There was no death in the 346 patients. (3) Analysis of prognosis of patients with synchro-nous colorectal liver metastasis in 2000?2010 and 2011?2021. Of the 346 patients, 295 cases were followed up for 47(range, 1?108)months. Of the 29 patients admitted in 2000?2010 who were followed up, there were 27 cases died. The median survival time, 1-, 3-, 5-year overall survival rates, 1-, 3-, 5-year disease free survival rates of patients admitted in 2000?2010 were 18.0 months (95% confidence interval as 12.7?23.3 months), 82.8%, 11.5%, 3.8%, 53.6%, 8.3%, 4.2%, respec-tively. Of the 266 patients admitted in 2011?2021 who were followed up, there were 109 cases died. The median survival time, 1-, 3-, 5-year overall survival rates, 1-, 3-, 5-year disease free survival rates of patients admitted in 2011?2021 were 54.0 months (95% confidence interval as 38.1?70.4 months), 93.3%, 61.8%, 47.0%, 68.2%, 33.7%, 28.3%, respectively. There were significant differences in overall survival rate and disease free survival rate between patients admitted in 2000?2010 and 2011?2021 ( χ2=47.57, 9.17, P<0.05). Conclusions:With the increase of the operation volume of simultaneous resection of synchronous colorectal liver metastasis, the operation time, time to postoperative initial liquid food intake, postoperative duration of hospital stay and postoperative complications have significantly decreased, while the overall survival rate and disease free survival rate have significantly increased.
9. Several suggestion of operation for colorectal cancer under the outbreak of Corona Virus Disease 19 in China
Guanyu YU ; Zheng LOU ; Wei ZHANG
Chinese Journal of Gastrointestinal Surgery 2020;23(3):9-11
Pneumonia caused by SARS-Cov-2 infection has been reported in Wuhan since December 2019, and spread rapidly across the country. The radical operation of colorectal cancer is confine operation. Patients with colorectal cancer should receive operation as soon as possible after elective operation is resumed in each hospital. SARS-Cov-2 virus can be transmitted by asymptomatic infectors, and it has been confirmed to be transmitted by droplets and contact. However, fecal-oral transmission and aerosol transmission have not been excluded. Based onLaparoscopic colorectal operation experiences, the author suggests that the surgery strategy for colorectal cancer patients under the COVID-19 situation. Recommending laparoscopy-assisted radical surgery for colorectal cancer patients. The aerosols need to be strictly managed during operation. NOSES and TaTME should be carried out with cautious during the epidemic period. Protective stoma should be carried out scientifically and reasonably, and the protection of operating room personnel should be strengthened.
10.A Preliminary study on the preoperative risk score system for simultaneous operation for patients with colorectal cancer and liver metastases
Jinke SUI ; Nanxin ZHENG ; Fuao CAO ; Guanyu YU ; Xiaoming ZHU ; Haifeng GONG ; Zheng LOU ; Liqiang HAO ; Ronggui MENG ; Wei ZHANG
Chinese Journal of Hepatobiliary Surgery 2020;26(7):522-525
Objective:This study aims to analyze the prognosis of patients who underwent a simultaneous operations for colorectal cancer and liver metastases, and to establish a prognostic scoring system for these patients.Methods:From January 2010 to March 2019, the clinicopathological data of patients with colorectal cancer and liver metastases simultaneously operated at Shanghai Changhai Hospital were collected. The clinicopathological prognostic factors on tumor recurrence and survival outcomes on follow-up were analyzed. Single and multiple factors Cox regression analyses were used to determine the risk factors which affected the prognosis of patients. Using the risk factors of poor prognosis on Cox analysis, 1 point was given to each risk factor. Patients were then divided into different groups according to the different total scores. The median overall survival and disease-free survival of each group were analyzed.Results:Of 234 patients included in this study, there were 126 males and 108 females. The average age was (57.4±10.8) years. The median survival was 44.85 months. The 1-, 3-, and 5-year survival rates of the whole group were 87.3%, 55.2%, and 22.9%, respectively. Primary tumor in right colon, preoperative carcinoembryonic antigen ≥200 ng/ml, multiple liver metastases, and poorly differentiated adenocarcinoma/mucinous adenocarcinoma were independent risk factors of poor prognosis. After 1 point was given to each of the above 4 items, patients were then divided into the low-risk (0-1) and high-risk (2-4) groups. The median survivals of patients in the low-risk group ( n=174) and high-risk group ( n=60) were 53 months and 29 months, respectively. The corresponding median disease-free survivals were 21.34 months and 8.48 months, respectively. The differences between the 2 groups were significant ( P<0.05). Conclusion:The results of this study preliminary established a predictive scoring system for patients with simultaneous colorectal cancer and liver which can play a role in selecting treatment options for these patients.

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