1.Analysis of the efficacy and safety of preoperative programmed death protein-1 inhibitor combined with chemotherapy in immunotherapy-sensitive patients with locally advanced gastric cancer or adenocarcinoma of the esophagogastric junction
Yingjie LI ; Peng YUAN ; Jianning ZHAI ; Yunfeng YAO ; Luxin TAN ; Zhongwu LI ; Xiaoyan ZHANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2024;27(7):684-693
Objective:To evaluate the short-term efficacy and safety of a preoperative combination of programmed cell death protein-1 (PD-1) inhibitor with either oxaliplatin + capecitabine (CapeOx) or oxaliplatin + tegafur gimeracil oteracil potassium (SOX) in the treatment of locally advanced immunotherapy-sensitive gastric cancer (LAGC) or adenocarcinoma of the esophagogastric junction (AEG).Methods:The cohort of this retrospective descriptive case series comprised patients with LAGC or AEG whose cancers had been determined to be immunotherapy- sensitive by endoscopic biopsy before treatment in the Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital and Institute from 1 August 1 2021 to 31 January 2024. Patients with any one of the following three characteristics were immunotherapy-sensitive: (i) PD-L1 combined positive score (CPS) ≥5; (ii) microsatellite instability-high (MSI-H) / mismatch repair deficiency (dMMR); or (iii) Epstein-Barr virus-encoded RNA (EBER) positivity. All study patients received PD-1 inhibitors combined with CapeOx or SOX as a neoadjuvant or conversion treatment strategy before surgery. Patients with immune system diseases, distant metastases, or human epidermal growth factor receptor 2 positivity were excluded. Factors analyzed included pathological complete response, clinical complete response, major pathological response, R0 resection rate, surgical conversion rate, and safety of the treatment, including immune-related adverse events (irAEs) and surgical complications.Results:The study cohort comprised 39 patients (28 men and 11 women) of median age 62 (range 44–79) years. After the above-described preoperative treatment, radical resection of the 14 tumors that were initially considered unresectable was achieved (surgical conversion rate: 14/14). Twenty-three of the remaining 25 patients underwent radical resection. The last two patients achieved clinical complete responses and opted for a "non-surgical strategy" (watch and wait). Overall, 37 patients (94.9%) underwent radical resection, with an R0 resection rate of 100% (37/37), pathological complete response rate of 48.6% (18/37), and major pathological response rate of 62.2% (23/37). Of the 24 patients with CPS ≥ 5 (non-MSI-H/dMMR and non-EBER positive), 11 achieved pathological complete responses and one with CPS=95 achieved a clinical complete response. Of the eight patients with MSI-H/dMMR, six achieved pathological complete responses and one a clinical complete response. Of the seven patients with EBER positivity, one achieved a pathological complete response. After excluding patients with major pathological complete responses, there was a statistically significant difference in CPS scores between preoperative biopsy specimens and postoperative surgical specimens in 13 patients (7.769±5.570 vs. 15.538±16.870, t=2.287, P=0.041). All patients tolerated preoperative immunotherapy well; nine patients (9/39, 23.1%) had Grade I–II irAEs. There were no Grade III–IV irAEs. The five patients with pyloric obstruction before treatment tolerated normal diets after treatment. The incidence of postoperative complications among all patients who underwent surgery was 18.9% (7/37), including one case of Grade IIIA anastomotic leakage, one of Grade IIIA intestinal obstruction, one of Grade II abdominal hemorrhage, two of Grade II abdominal infection, one of Grade I intestinal obstruction. Additionally, one patient developed COVID-19 postoperatively. All patients recovered with symptomatic treatment. Conclusion:We found that preoperative treatment of patients with LAGC or AEG of one of three types (CPS≥5, dMMR+MSI-H, and EBER positivity) with a PD-1 inhibitor combined with CapeOx or SOX chemotherapy achieved promising effectiveness and safety, with high surgical conversion, R0 resection, and complete response rates.
2.Clinical features and prognostic analysis of colorectal extranodal NK/T cell lymphoma
Xiangyu LI ; Jianning YAO ; Xuyang DONG ; Liangxing CHENG ; Xuexiu ZHANG ; Mengge SU ; Haining ZHOU ; Jinlin XIE ; Zhaoxiang SONG ; Fei HAN
Chinese Journal of Oncology 2024;46(8):782-793
Objective:To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma.Methods:The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model.Results:Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome ( HR=8.50,95% CI: 1.679-8.328, P=0.001), serum albumin ( HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy ( HR=0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions:Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.
3.Standardized procedures and quality control in laparoscopic right hemicolectomy for right-sided colon cancer
Hongwei YAO ; Pengyu WEI ; Wenlong SHU ; Si WU ; Hanzheng ZHAO ; Jianning SONG ; Guocong WU ; Zhongtao ZHANG
Chinese Journal of Digestive Surgery 2024;23(6):770-774
Laparoscopic right hemicolectomy is currently the most commonly used surgical procedure for right-sided colon cancer. Although this procedure is maturing in terms of key tech-niques such as the extent of surgical resection, the extent of lymph node dissection, and the recons-truction of digestive tract, it still lacks a standardized surgical procedure and quality control system. In the pre-preparation phase of the COLOR Ⅳ study (an international, multicenter, randomized contro-lled trail comparing the efficacy of intracorporeal anastomosis versus extracorporeal anasto-mosis in laparoscopic right hemicolectomy for right-sided colon cancer), the research team of the authors formulates a standardized procedure for laparoscopic right hemicolectomy based on the Delphi survey, and develops a competency assessment tool for surgical ability and quality. Attempts are being made to automate the evaluation of surgical techniques using artificial intelligence. It is hoped that the above work will help colorectal surgeons to standardize surgical operations and reduce complications, provide support for the homogenization of multicenter clinical studies, and promote the implementation of structured training for this procedure.
4.Biomechanical analysis of calcaneal sustentaculum tail sustentacular screw in treatment of Sanders type Ⅱ fractures
Guangsheng TANG ; Qi WANG ; Yao XU ; Bing WANG ; Jianning SUN ; Deguang WANG
International Journal of Biomedical Engineering 2024;47(5):449-456
Objective:To construct a finite element analysis model for the application of sustentaculum tail sustentacular screw in the treatment of calcaneal fracture of Sanders type Ⅱ. The finite element analysis method was used to study the effectiveness of the simulation treatment of Sanders type Ⅱ calcaneal fracture.Methods:A complete adult calcaneal specimen that was not affecting the normal quality of bone after teaching in the Department of Human Anatomy, Kangda College of Nanjing Medical University from 2021 to 2022 second semester was selected. A micro CT scan was performed to obtain data. The three-dimensional model of the calcaneus was reconstructed by the software of Mimics and Geomagic Wrap. The internal fixation and fracutre model were drawn using SolidWorks software. The obtained data were imported into the finite element analysis software for material assignment and meshing to obtain a three-dimensional finite element model. The load and boundary constraints were applied to each model to perform finite element analysis and calculation, and the stress and displacement of the model were extracted. Finally, the experimental screw placement of the calcaneus loading process was verified.Results:The three-dimensional model of calcaneal fracture had a high degree of appearance simulation, complete morphological structure, no defect, and was consistent with the size of the solid calcaneus. After surgical treatment, the anatomical reduction of each fracture model was good, the steel plate fit to the bone surface, and the screw did not protrude outside the model. There was no deformation or damage to the whole internal fixation, the grid division was clear, and the number was relatively uniform and consistent. The maximum stress in each type of calcaneal fracture model was in the internal fixation, and the overall stress was uniformly distributed in each component. The maximum displacement distance of each type of calcaneal fracture was less than 0.13 mm, and the angles and lengths of nails were accurate. The tip of the Kirschner wires was located in the sustentaculum tail. There was no rupture of the sustentaculum tali and no protrusion of the Kirschner wires.Conclusions:The internal fixation is an effective method to treat the Sanders type Ⅱ calcaneal fractures by using sustentaculum tail sustentacular screws.
5.Target gene prediction and related pathway analysis of miR-223-3p in high glucose induced H9c2 cell injury
Jianning QIN ; Yang HAN ; Yao TAN ; Letian YU ; Shunlin QU
Chinese Journal of Arteriosclerosis 2024;32(11):947-954
Aim The effect of miR-223-3p on H9c2 cells in high glucose environments was investigated through bioinformatics and its role in the mechanism of development of diabetic cardiomyopathy was analyzed in conjunction with transcriptomic sequencing results.The objective was to identify novel therapeutic targets at the molecular level and explore the specific mechanisms of action of miR-223-3p.Methods In high glucose-cultivated H9c2 cells,miR-223-3p inhibition and control were transfected,respectively.RT-qPCR was used to detect the differences in miR-222-3p expression between the two cell groups.Differential mRNA was identified through high-throughput sequen-cing.GO functional analysis was conducted using TopGO software.DESeq2 software(v1.16.1)filtered differentially expressed genes and analyzed them using a miR-223-3p target gene database.This process predicted the target genes of miR-223-3p and validated the changes in their expression through RT-qPCR.Results The activity of H9c2 cells trea-ted with high glucose decreased significantly.Significant differences in gene expression between the control group and the inhibitor group had been indicated by transcriptomic sequencing results.GO function enrichment analysis showed that the predicted target gene set was significantly enriched in G protein-coupled receptor activity,glycerol ether monooxygenase ac-tivity,cellular anion homeostasis,and chloride ion homeostasis,among others.KEGG pathway enrichment analysis fur-ther showed that these genes were mainly involved in the TNF signaling pathway and the IL-17 signaling pathway.In ad-dition,they were related to type 1 diabetes,cytochrome P450 metabolism of exogenous drugs,and other diseases and phys-iological processes.Target gene prediction suggested that miR-223-3p may be associated with the expression changes of Cxcl10,Creb313,Mmp3,and Bc13,among others.Conclusion The prediction of miR-223-3p and its downstream target genes in high glucose induced H9c2 cell injury may provide new targets for the treatment of diabetic cardiomyopa-thy,which is of great significance for revealing the pathogenesis of diabetic cardiomyopathy and developing new treatment strategies.
6.Analysis of the efficacy and safety of preoperative programmed death protein-1 inhibitor combined with chemotherapy in immunotherapy-sensitive patients with locally advanced gastric cancer or adenocarcinoma of the esophagogastric junction
Yingjie LI ; Peng YUAN ; Jianning ZHAI ; Yunfeng YAO ; Luxin TAN ; Zhongwu LI ; Xiaoyan ZHANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2024;27(7):684-693
Objective:To evaluate the short-term efficacy and safety of a preoperative combination of programmed cell death protein-1 (PD-1) inhibitor with either oxaliplatin + capecitabine (CapeOx) or oxaliplatin + tegafur gimeracil oteracil potassium (SOX) in the treatment of locally advanced immunotherapy-sensitive gastric cancer (LAGC) or adenocarcinoma of the esophagogastric junction (AEG).Methods:The cohort of this retrospective descriptive case series comprised patients with LAGC or AEG whose cancers had been determined to be immunotherapy- sensitive by endoscopic biopsy before treatment in the Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital and Institute from 1 August 1 2021 to 31 January 2024. Patients with any one of the following three characteristics were immunotherapy-sensitive: (i) PD-L1 combined positive score (CPS) ≥5; (ii) microsatellite instability-high (MSI-H) / mismatch repair deficiency (dMMR); or (iii) Epstein-Barr virus-encoded RNA (EBER) positivity. All study patients received PD-1 inhibitors combined with CapeOx or SOX as a neoadjuvant or conversion treatment strategy before surgery. Patients with immune system diseases, distant metastases, or human epidermal growth factor receptor 2 positivity were excluded. Factors analyzed included pathological complete response, clinical complete response, major pathological response, R0 resection rate, surgical conversion rate, and safety of the treatment, including immune-related adverse events (irAEs) and surgical complications.Results:The study cohort comprised 39 patients (28 men and 11 women) of median age 62 (range 44–79) years. After the above-described preoperative treatment, radical resection of the 14 tumors that were initially considered unresectable was achieved (surgical conversion rate: 14/14). Twenty-three of the remaining 25 patients underwent radical resection. The last two patients achieved clinical complete responses and opted for a "non-surgical strategy" (watch and wait). Overall, 37 patients (94.9%) underwent radical resection, with an R0 resection rate of 100% (37/37), pathological complete response rate of 48.6% (18/37), and major pathological response rate of 62.2% (23/37). Of the 24 patients with CPS ≥ 5 (non-MSI-H/dMMR and non-EBER positive), 11 achieved pathological complete responses and one with CPS=95 achieved a clinical complete response. Of the eight patients with MSI-H/dMMR, six achieved pathological complete responses and one a clinical complete response. Of the seven patients with EBER positivity, one achieved a pathological complete response. After excluding patients with major pathological complete responses, there was a statistically significant difference in CPS scores between preoperative biopsy specimens and postoperative surgical specimens in 13 patients (7.769±5.570 vs. 15.538±16.870, t=2.287, P=0.041). All patients tolerated preoperative immunotherapy well; nine patients (9/39, 23.1%) had Grade I–II irAEs. There were no Grade III–IV irAEs. The five patients with pyloric obstruction before treatment tolerated normal diets after treatment. The incidence of postoperative complications among all patients who underwent surgery was 18.9% (7/37), including one case of Grade IIIA anastomotic leakage, one of Grade IIIA intestinal obstruction, one of Grade II abdominal hemorrhage, two of Grade II abdominal infection, one of Grade I intestinal obstruction. Additionally, one patient developed COVID-19 postoperatively. All patients recovered with symptomatic treatment. Conclusion:We found that preoperative treatment of patients with LAGC or AEG of one of three types (CPS≥5, dMMR+MSI-H, and EBER positivity) with a PD-1 inhibitor combined with CapeOx or SOX chemotherapy achieved promising effectiveness and safety, with high surgical conversion, R0 resection, and complete response rates.
7.Clinical features and prognostic analysis of colorectal extranodal NK/T cell lymphoma
Xiangyu LI ; Jianning YAO ; Xuyang DONG ; Liangxing CHENG ; Xuexiu ZHANG ; Mengge SU ; Haining ZHOU ; Jinlin XIE ; Zhaoxiang SONG ; Fei HAN
Chinese Journal of Oncology 2024;46(8):782-793
Objective:To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma.Methods:The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model.Results:Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome ( HR=8.50,95% CI: 1.679-8.328, P=0.001), serum albumin ( HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy ( HR=0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions:Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.
8.Retrospective cohort study on prognosis impact of preoperative obstruction in colorectal cancer
Jianning SONG ; Zhigang BAI ; Jun LI ; Yun YANG ; Guocong WU ; Hongwei YAO ; Jin WANG ; Lan JIN ; Dong WANG ; Zhongtao ZHANG ; Yingchi YANG
International Journal of Surgery 2022;49(5):327-332,C2
Objective:To investigate the effect of obstruction on the prognosis and possible mechanisms in colorectal cancer patients.Methods:Among 1574 cases of colorectal cancer who were treated in Beijing Friendship Hospital, Capital Medical University from January 2003 to December. 2014, 194 cases had preoperative intestinal obstruction. Firstly, described the clinical characteristics of 194 patients with obstruction, then COX multivariate regression analysis was performed on the 1574 colorectal cancer cohort to confirm whether the preoperative obstruction was independent predictor for the overall survival. Finally, propensity score matching method was used to match obstruction and non-obstruction cases, then compared overall survival difference.Results:In 194 cases of obstructive colorectal cancer, 60.3% and 37.1% of the tumors were located in the left and right respectively. The 55.7% of the patients had tumors larger than 5 cm in diameter, the median survival time was 39.7 months (95% CI: 28.3-60.4). Multivariate COX analysis, after adjusted for related confounding factors, found that preoperative obstruction is still an independent risk factor for poor prognosis ( HR=1.41, 95% CI: 1.01-1.97). After propensity score matching, 140 and 560 patients were included in the obstructive group and the non-obstructive group. The two groups were more balanced in most baseline characteristics. The median survival time of the two groups was 42.4 and 116.3 months ( P<0.001), the overall survival of obstructive patients was significantly worse than that of non-obstructive patients. Conclusions:Preoperative obstruction is an independent risk factor for poor prognosis of colorectal cancer. This may be due to the difficulty of surgery and low radical cure rate for obstructive colorectal cancer.
9.Study on the risk factors of type 1 gastric neuroendocrine tumor in 123 cases of autoimmune gastritis
Mengge SU ; Xuyang DONG ; Xuexiu ZHANG ; Ya LI ; Haining ZHOU ; Xiangyu LI ; Jianning YAO
Chinese Journal of Digestion 2022;42(10):675-680
Objective:To investigate the risk factors of type 1 gastric neuroendocrine tumor (g-NET) in patients with autoimmune gastritis(AIG).Methods:From September 1, 2016 to February 28, 2022, 123 patients with AIG visited the First Affiliated Hospital of Zhengzhou University were retrospectively enrolled, including 37 cases with type 1 g-NET and 86 cases without type 1g-NET. The clinical data, serological indicators, and endoscopic manifestation of all the patients were analyzed, including the age at the time of AIG diagnosis (hereinafter referred to as the age at diagnosis), levels of gastrin 17 and pepsinogen Ⅰ (PGⅠ), presence or absence of gastric fundus and gastric body polyps, etc. The independent risk factors of type 1 g-NET in AIG patients were analyzed by univariate and multivariate logistic regression. The receiver operating characteristic curve (ROC) was plotted to analyze the optimal cut-off value, sensitivity and specificity of the independent risk factors in predicting type 1 g-NET in AIG patients. Independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:Compared with those of the AIG patients without type 1 g-NET, the age at diagnosis of AIG patients with type 1 g-NET was younger ((57.49±11.16) years old vs. (48.49±10.96) years old), the level of gastrin 17 was higher (200.21 ng/L, 121.85 ng/L to 244.40 ng/L vs. 244.40 ng/L, 182.50 ng/L to 248.02 ng/L), and the proportion of patients with gastric fundus and gastric body polyps was higher(18.6%, 16/86 vs. 56.8%, 21/37), and the differences were statistically significant( t=-4.13, Z=-3.06, χ2=17.90; P<0.001, =0.002 and <0.001). The results of univariate logistic analysis showed that the age at diagnosis ( OR=0.931, 95% confidence interval (95% CI)0.895 to 0.967), gastrin 17( OR=1.012, 95% CI 1.005 to 1.019), PGⅠ( OR=0.974, 95% CI 0.950 to 0.998)and gastric fundus and gastric body polyps( OR=5.742, 95% CI 2.461 to 13.399)were the influencing factors of type 1 g-NET in AIG patients ( P<0.001, =0.001, =0.033 and <0.001). The results of multivariate logistic regression analysis indicated that the age at diagnosis( OR=0.921, 95% CI 0.881 to 0.964), gastrin 17( OR=1.011, 95% CI 1.001 to 1.020), gastric fundus and gastric body polyps( OR=7.696, 95% CI 2.710 to 21.857)were the independent risk factors of type 1 g-NET in AIG patients ( P<0.001, =0.024 and <0.001). The results of ROC analysis demonstrated that the optimal cut-off values for the age at diagnosis and gastrin 17 in predicting type 1 g-NET were 56.50 years old and 206.40 ng/L, respectively; with sensitivity of 83.8% and 70.3%, respectively, and specificity of 54.7% for both ( P<0.001 and=0.003). Conclusion:The age at diagnosis< 56.50 years old, gastrin 17>206.40 ng/L and the presence of gastric fundus and gastric body polyps are independent risk factors of type 1 g-NET in AIG patients.
10.Efficacy of dual stent-assisted coil embolization in ruptured vertebral artery dissecting aneurysms
Lei WANG ; Jianhuang HUANG ; Tiaohua HUANG ; Jinjia LIN ; Jianning CHEN ; Jianhua SONG ; Zhengjian YAO
Chinese Journal of Neuromedicine 2022;21(3):273-277
Objective:To evaluate the safety and efficacy of dual stent-assisted coil embolization in intracranial ruptured vertebral artery dissecting aneurysms (VADAs).Methods:Seventeen patients with intracranial ruptured VADAs (17 aneurysms), treated with dual stent-assisted coil embolization in our hospital from September 2015 to March 2020, were recruited. DSA was performed immediately after surgery to evaluate the embolization degrees of VADAs. At the end of follow-up, modified Rankin scale (mRS) was used to evaluate the prognoses of these patients, and DSA was used to determine the healing status of aneurysms.Results:The postoperative immediate DSA showed that total occlusion was achieved in 6 patients (35.3%), subtotal occlusion in 8 (47.1%) and partial occlusion in 3 (17.6%). Two patients died during the perioperative period and 2 patients presented symptoms of cranial nerve palsy after surgery. Fifteen patients were followed up for 5-24 months, 14 were with good prognosis, and one was with poor prognosis. Eleven patients underwent DSA follow-up, which showed that 8 aneurysms healed completely, 2 aneurysms were stable, and 1 aneurysm recurred.Conclusion:Dual stent-assisted coil embolization may be an effective and safe treatment method for intracranial ruptured VADAs.

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