1.Clinical characteristics and prognosis of male dermatomyositis patients with positive anti-melanoma differentiation associated gene 5 antibody
Yitian SHI ; Fenghong YUAN ; Ting LIU ; Wenfeng TAN ; Ju LI ; Min WU ; Zhanyun DA ; Hua WEI ; Lei ZHOU ; Songlou YIN ; Jian WU ; Yan LU ; Dinglei SU ; Zhichun LIU ; Lin LIU ; Longxin MA ; Xiaoyan XU ; Yinshan ZANG ; Huijie LIU ; Tianli REN
Chinese Journal of Rheumatology 2024;28(1):44-49
Objective:To investigate the clinical features and prognosis of male with anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody.Methods:The clinical data of 246 patients with DM and anti-MDA5 autoantibodies hospitalized by Jiangsu Myositis Cooperation Group from 2017 to 2020 were collected and retrospectively analyzed. Chi-square test was performed to compared between counting data groups; Quantitative data were expressed by M ( Q1, Q3), and rank sum test was used for comparison between groups; Single factor survival analysis was performed by Kaplan-Meier method and Log rank test; Cox regression analysis were used for multivariate survival analysis. Results:①The male group had a higher proportion of rash at the sun exposure area [67.1%(47/70) vs 52.8%(93/176), χ2=4.18, P=0.041] and V-sign [50.0%(35/70) vs 30.7%(54/176), χ2=8.09, P=0.004] than the female group. The male group had higher levels of creatine kinase [112(18, 981)U/L vs 57 (13.6, 1 433)U/L, Z=-3.50, P<0.001] and ferritin [1 500 (166, 32 716)ng/ml vs 569 (18, 14 839)ng/ml, Z=-5.85, P<0.001] than the female group. The proportion of ILD [40.0%(28/70) vs 59.7%(105/176), χ2=7.82, P=0.020] patients and the red blood cell sedimentation rate[31.0(4.0, 101.5)mm/1 h vs 43.4(5.0, 126.5)mm/1 h, Z=-2.22, P=0.026] in the male group was lower than that of the female group, but the proportion of rapidly progressive interstitial lung disease (PR-ILD) [47.1%(33/70) vs 31.3%(55/176), χ2=5.51, P=0.019] was higher than that of the female group. ②In male patients with positive anti-MDA5 antibodies,the death group had a shorter course of disease[1.0(1.0, 3.0) month vs 2.5(0.5,84) month, Z=-3.07, P=0.002], the incidence of arthritis [16.7%(4/24) vs 42.2%(19/45), χ2=4.60, P=0.032] were low than those in survival group,while aspartate aminotransferase (AST)[64(22.1, 565)U/L vs 51(14,601)U/L, Z=-2.42, P=0.016], lactate dehydrogenase (LDH) [485(24,1 464)U/L vs 352(170, 1 213)U/L, Z=-3.38, P=0.001], C-reactive protein (CRP) [11.6(2.9, 61.7) mg/L vs 4.95(0.6, 86.4) mg/L, Z=-1.96, P=0.050], and ferritin levels [2 000(681, 7 676) vs 1 125 (166, 32 716)ng/ml, Z=-3.18, P=0.001] were higher than those in the survival group, and RP-ILD [95.8%(23/24) vs 22.2%(10/45), χ2=33.99, P<0.001] occurred at a significantly higher rate. ③Cox regression analysis indicated that the course of disease LDH level, and RP-ILD were related factors for the prognosis of male anti-MDA5 antibodies [ HR (95% CI)=0.203(0.077, 0.534), P=0.001; HR (95% CI)=1.002(1.001, 1.004), P=0.003; HR (95% CI)=95.674 (10.872, 841.904), P<0.001]. Conclusion:The clinical manifestations of male anti-MDA5 antibody-positive patients are different from those of female. The incidence of ILD is low, but the proportion of PR-ILD is high. The course of disease, serum LDH level, and RP-ILD are prognostic factors of male anti-MDA5 antibody-positive patients.
2.Value of multi-sequence MRI radiomics combined with KRAS mutation nomogram model in predicting the sensitivity of neoadjuvant chemotherapy in patients with rectal cancer
Hongbo HU ; Ying ZHANG ; Sheng ZHAO ; Hao JIANG ; Xue LIN ; Huijie JIANG
Chinese Journal of Radiology 2024;58(10):1069-1074
Objective:To construct a multi-sequence MRI radiomics combined with KRAS mutation nomogram model to predict the efficacy of pathological complete response (pCR) in patients with rectal cancer after neoadjuvant chemoradiotherapy.Methods:This study was a case-control study. A total of 126 patients with rectal cancer who were treated with neoadjuvant chemoradiotherapy in the Second Affiliated Hospital of Harbin Medical University from June 2020 to December 2023 were retrospectively collected. The pathological response of the postoperative specimens was graded, with 64 cases of pCR and 62 cases of non-pCR. KRAS gene detection was performed on the pathological tissues before neoadjuvant chemoradiotherapy. Among the patients, 34 cases had KRAS mutants and 92 cases had KRAS wild-types. The 126 patients were randomly divided into a training set and a validation set at a ratio of 8∶2 by the random number method, with 101 and 25 cases, respectively. The difference in KRAS mutation status between the pCR group and the non-pCR group was compared by the χ2 test. The radiomic features were extracted from the baseline T 2WI, diffusion-weighted imaging, and apparent diffusion coefficient images of the patients. The optimal radiomic features were screened out to establish the radiomics model. The radiomics-KRAS joint model was constructed by logistic regression, and a nomogram was drawn. The application efficiency of the model was evaluated by the receiver operating characteristic curve and calibration curve. Results:There was a statistically significant difference in KRAS mutation between the pCR group and the non-pCR group in the training set ( χ2=4.69, P=0.032). Ten radiomics features were screened out in MRI images to establish the radiomics model. In the training set and validation set, the areas under the curve (AUC) of KRAS mutation, radiomics model and radiomics-KRAS nomogram model for evaluating pCR after neoadjuvant chemoradiotherapy were 0.665 (95% CI 0.592-0.757), 0.746 (95% CI 0.651-0.895) and 0.818 (95% CI 0.742-0.934), respectively, and the AUCs of the validation set were 0.613 (95% CI 0.582-0.755), 0.738 (95% CI 0.627-0.839) and 0.833 (95% CI 0.768-0.961), respectively. The results of DeLong test showed that the AUC of radiomics-KRAS nomogram model was higher than that of KRAS mutation and radiomics model, and the difference was statistically significant ( Z=0.58, 0.63, P=0.024, 0.022 in the training set; Z=0.54, 0.61, P=0.018, 0.035 in the validation set). The calibration curve showed that the predicted probability of the radiomics-KRAS nomogram model was consistent with the actual probability. Conclusions:The multi-sequence MRI radiomics combined with the KRAS mutation nomogram model has the best efficacy in predicting pCR in patients with rectal cancer after neoadjuvant chemoradiotherapy, and has good practical application value.
3.Investigation and analysis of work-related musculoskeletal disorders among scientific researchers in computer workstation of an aerospace high-tech enterprise
Yingwu CUI ; Huijie ZHANG ; Shumao LIN ; Jing BAO ; Shaohui HAN ; Huining WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(11):837-844
Objective:To analyze the current situation and influencing factors of work-related musculoskeletal disorders (WMSDs) among scientific researchers in a computer workstation of a high-tech aerospace enterprise, and to provide data support for the improvement of occupational health management policies in this type of enterprise.Methods:From March to April 2023, using convenient sampling method, 1398 scientific researchers using computer workstations in an aerospace high-tech enterprise in Beijing were selected as the research subjects. The incidence of WMSDs in various parts of the body was investigated by using the Musculoskeletal Disorders Questionnaire, and the influencing factors of WMSDs in neck, lower back, shoulder and upper back were analyzed by logistic regression.Results:The total incidence of WMSDs was 55.4% (774/1398) in the scientific researchers who used computer workstations. The top 4 body parts in WMSDs incidence were neck (24.3%, 340/1398), lower back (20.4%, 285/1398), shoulder (18.7%, 262/1398), upper back (12.7%, 177/1398). The results of multivariate logistic regression analysis showed that feeling slightly tired and tired after work, setting a rest/break time of 10 to 15 min before the next continuous job, and operating computer for 2 to 4 hours and >4 hours were the influencing factors for the occurrence of neck WMSDs ( OR=3.08, 1.90, 0.60, 2.00, 1.49, P<0.05). Female, 5-<10 years of working experience, feeling slightly tired, tired and very tired after work, operating computer for 6-<8 hours and 8-10 hours a day were all the influencing factors for the occurrence of WMSDs in the lower back ( OR=1.82, 0.64, 2.95, 1.80, 1.61, 1.82, 1.73, P<0.05). Female, feeling slightly tired and tired after work were the influencing factors of shoulder WMSDs occurrence ( OR=2.42, 2.09, 2.00, P<0.05). Female, 5-<10 years, 10-15 years of working age, 1-3 times of physical exercise/quarter, feeling slightly tired, tired and very tired after work were the influencing factors for the occurrence of upper back WMSDs ( OR=2.76, 2.19, 2.78, 0.48, 4.20, 2.66, 2.19, P<0.05) . Conclusion:The incidence of WMSDs among scientific researchers in computer workstations of aerospace high-tech enterprises is high, which is closely related to individual characteristics and workstation usage characteristics. Measures should be taken to prevent and improve the WMSDs status of scientific researchers.
4.Bidirectional relationship between type 2 diabetes mellitus and coronary artery disease: Prospective cohort study and genetic analyses
Wenqiang ZHANG ; Li ZHANG ; Chenghan XIAO ; Xueyao WU ; Huijie CUI ; Chao YANG ; Peijing YAN ; Mingshuang TANG ; Yutong WANG ; Lin CHEN ; Yunjie LIU ; Yanqiu ZOU ; Ling ZHANG ; Chunxia YANG ; Yuqin YAO ; Jiayuan LI ; Zhenmi LIU ; Xia JIANG ; Ben ZHANG
Chinese Medical Journal 2024;137(5):577-587
Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.
5.Investigation and analysis of work-related musculoskeletal disorders among scientific researchers in computer workstation of an aerospace high-tech enterprise
Yingwu CUI ; Huijie ZHANG ; Shumao LIN ; Jing BAO ; Shaohui HAN ; Huining WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(11):837-844
Objective:To analyze the current situation and influencing factors of work-related musculoskeletal disorders (WMSDs) among scientific researchers in a computer workstation of a high-tech aerospace enterprise, and to provide data support for the improvement of occupational health management policies in this type of enterprise.Methods:From March to April 2023, using convenient sampling method, 1398 scientific researchers using computer workstations in an aerospace high-tech enterprise in Beijing were selected as the research subjects. The incidence of WMSDs in various parts of the body was investigated by using the Musculoskeletal Disorders Questionnaire, and the influencing factors of WMSDs in neck, lower back, shoulder and upper back were analyzed by logistic regression.Results:The total incidence of WMSDs was 55.4% (774/1398) in the scientific researchers who used computer workstations. The top 4 body parts in WMSDs incidence were neck (24.3%, 340/1398), lower back (20.4%, 285/1398), shoulder (18.7%, 262/1398), upper back (12.7%, 177/1398). The results of multivariate logistic regression analysis showed that feeling slightly tired and tired after work, setting a rest/break time of 10 to 15 min before the next continuous job, and operating computer for 2 to 4 hours and >4 hours were the influencing factors for the occurrence of neck WMSDs ( OR=3.08, 1.90, 0.60, 2.00, 1.49, P<0.05). Female, 5-<10 years of working experience, feeling slightly tired, tired and very tired after work, operating computer for 6-<8 hours and 8-10 hours a day were all the influencing factors for the occurrence of WMSDs in the lower back ( OR=1.82, 0.64, 2.95, 1.80, 1.61, 1.82, 1.73, P<0.05). Female, feeling slightly tired and tired after work were the influencing factors of shoulder WMSDs occurrence ( OR=2.42, 2.09, 2.00, P<0.05). Female, 5-<10 years, 10-15 years of working age, 1-3 times of physical exercise/quarter, feeling slightly tired, tired and very tired after work were the influencing factors for the occurrence of upper back WMSDs ( OR=2.76, 2.19, 2.78, 0.48, 4.20, 2.66, 2.19, P<0.05) . Conclusion:The incidence of WMSDs among scientific researchers in computer workstations of aerospace high-tech enterprises is high, which is closely related to individual characteristics and workstation usage characteristics. Measures should be taken to prevent and improve the WMSDs status of scientific researchers.
6.Mechanism of action and research progress of vaccine adjuvants
Li ZHANG ; Chang LU ; Minghui AN ; Mengmeng WANG ; Xiaoyu ZONG ; Lin YU ; Zhuo-Ling RAN ; Jing SONG ; Huijie LI ; Jian GONG
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(7):785-791
Vaccines are among the most effec-tive measures for preventing infectious diseases and play a crucial role in controlling the spread of these diseases.Adjuvants,serving as auxiliary com-ponents in vaccines,are indispensable in the vac-cine development process.Ideal adjuvants not only enhance the immune response,enabling the body to achieve optimal protective immunity but also play important roles in reducing the dosage of im-munogens and lowering vaccine production costs.To meet the demands of novel vaccines,many new types of adjuvants have been developed.However,there is still a lack of adjuvants that are safe,effec-tive,easy to prepare,highly pure,and suitable for a variety of vaccines in clinical settings.This article categorizes adjuvants and summarizes their mecha-nisms of action and characteristics,focusing on tra-ditional aluminum salt adjuvants and more modern lipid-based and nucleic acid-based adjuvants.The summary is based on a computer search of data-bases including PubMed,Embase,The Cochrane Li-brary,CNKI(China National Knowledge Infrastruc-ture),VIP Database,and Wanfang Database,using English search keywords such as Adjuvants,Vac-cine,Vaccine Adjuvant,aluminum salts,MF59,AS03,Toll-like receptor agonist,etc.,and corre-sponding Chinese search terms.The aim is to pro-vide references for the development and applica-tion of adjuvants.
7.Effect of oxygen blowing combined with clostridium butyricum and bifidobacterium powders in neonatal diaper dermatitis
Xia WANG ; Huijie XU ; Lin YANG
China Pharmacist 2024;28(11):445-450
Objective To explore the clinical efficacy of oxygen blowing combined with clostridium butyricum and bifidobacterium powders in neonatal diaper dermatitis(DD).Methods Data of neonatal DD patients admitted to the Department of Pediatrics of the Affiliated Hospital of Hangzhou Normal University from January 2019 to June 2021 were retrospectively analyzed.They were divided into the control group(oxygen blowing)and the experimental group(oxygen blowing combined with clostridium butyricum and bifidobacterium powders)according to whether or not they received clostridium butyricum and bifidobacterium powders treatment.The primary efficacy index of the study was the treatment efficiency,and the secondary efficacy indexes were the severity of DD(Neonatal Rash Scale score,DD score,and lesion area score),time to erythema resolution,time to vesicle resolution,and time to healing.Results A total of 99 patients were included in the study,with 42 in the experimental group and 57 in the control group.The treatment efficiency of the experimental group was significantly higher than that of the control group(P<0.05).With regard to the severity of DD,the papule and pustule scores,dermatitis extent scores,erythema severity scores,skin damage scores and lesion area scores of the experimental group were significantly lower than those of the control group(P<0.05);the proportions of moderate and severe syndrome in the experimental group were lower than those of the control group(P<0.05).The time for erythema to subside,the time for vesicles to subside and the time for healing were shorter in the experimental group than in the control group(P<0.05).Conclusion Oxygen blowing combined with clostridium butyricum and bifidobacterium powders can significantly improve the clinical effect of neonatal DD,but the specific mechanism still needs to be explored.
8.Prediction of CT-Based Radiomics in T1 Peripheral Non-Small Cell Lung Cancer via Spread Though Air Spaces
Huijie GE ; Yujuan CAO ; Lin WANG ; Juan GUO ; Shuai QUAN ; Linning E
Chinese Journal of Medical Imaging 2024;32(7):674-681
Purpose To investigate the predictive value of chest CT-based radiomics for spread through air spaces in stage T1 peripheral type lung cancer.Materials and Methods A total of 173 patients with surgically pathologically confirmed stage T1 non-small cell lung cancer were retrospectively collected and divided into positive group(49 cases)and negative group(124 cases)according to the presence or absence of spread through air spaces.All lesions were randomly divided into training set(122 cases)and validation set(51 cases)according to the ratio of 7∶3.The primary area of lung cancer(the main body of the lesion),the peripheral infiltrative area(a 5-mm annular area expanding outward along the edge of the lesion)and the tumor margin area(a 5-mm annular area retracting inward along the edge of the lesion)were used as areas of interest to extract imaging histological features.Three imaging histological models were established for the primary area of lung cancer,the peripheral infiltrative area and the tumor margin area,and combined with the morphological features of CT to establish three combined models.The efficacy of each model was evaluated and the optimal model was selected.Results The lobulation signs of positive group was significantly more than that of negative group(χ2=9.946,P=0.002).The area under the curve(AUC)of the imaging histological model based on the three regions of interest were 0.899,0.825,0.840 for the training group and 0.876,0.811 and 0.832 for the validation group,respectively.The model with the highest AUC was the primary tumor imaging model(P=0.043,P<0.001,P=0.017),the AUC of the combined model established by adding the lobar sign were 0.917,0.835 and 0.851,respectively.The AUC of the three regions of interest in the validation group were 0.912,0.832,and 0.845 and the highest AUC was found in the primary tumor area(P<0.001,P=0.017,P=0.049).Conclusion It is feasible to study lung cancer with airway metastasis via CT-based radiomics,taken lobulation signs as the risk predictive factor.
9.Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C
Ping ZHU ; Shi-You LI ; Jin DING ; Zhou FEI ; Sheng-Nan SUN ; Zhao-Hui ZHENG ; Ding WEI ; Jun JIANG ; Jin-Lin MIAO ; San-Zhong LI ; Xing LUO ; Kui ZHANG ; Bin WANG ; Kun ZHANG ; Su PU ; Qian-Ting WANG ; Xin-Yue ZHANG ; Gao-Liu WEN ; Jun O.LIU ; Thomas-John AUGUST ; Huijie BIAN ; Zhi-Nan CHEN ; You-Wen HE
Journal of Pharmaceutical Analysis 2023;13(6):616-624
Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.
10.Effects of Mangiferin on Glucose and Lipid Metabolism of Insulin-resistant HepG2 Cells
Zilin LI ; Huijie JIN ; Jia FANG ; Yiming LIU ; Aihua LIN
China Pharmacy 2021;32(9):1082-1088
OBJECTIVE:To analyze the effects of mangiferin (MGF)on glucose and lipid metabolism in insulin resistance (IR)HepG2 cells,and to explore the potential mechanism. METHODS :Using human hepatoma HepG 2 cells as research objects , 1 mmol/L palmitic acid and 2 mmol/L oleic acid were used to establish the IR-HepG 2 cell model. Using metformin hydrochloride as positive control ,the effects of low-concentration ,medium-concentration and high-concentration MGF (125,250,500 μmol/L)on the corrected glucose consumption ,the contents of triglyceride (TG)and total cholesterol (TC)in IR-HepG 2 cells were detected. The mRNA expression of APN ,AdipoR2,APPL1,AMPK in the upstream of AMPK signaling pathway and IRS- 1,Akt and GLUT4 in the downstream insulin signaling pathway were detected by RT-PCR. The phosphorylation level of AMPK protein was detected by Western blot assay. RESULTS :Compared with control group ,corrected glucose consumption ,mRNA expression of APN,AdipoR2,APPL1,AMPK,IRS-1 and GLUT 4,as well as the phosphorylation level of AMPK protein were decreased significantly in model group ,while the contents of TG and TC were increased significantly (P<0.05 or P<0.01). Compared with model group , corrected glucose consumption , mRNA expression of APN (except for MGF medium-concentration and high-concentration groups ),AdipoR2,APPL1,AMPK(except for MGF medium-concentration and high-concentration groups ), IRS-1(except for MGF medium-concentration and high-concentration groups ),Akt(except for positive control group ),GLUT4 (except for MGF high-concentration group )were increased significantly in administration groups ,while the contents of TG and TC were decreased significantly (P<0.05 or P<0.01). CONCLUSIONS :Mangiferin may activate APN ,which is the upstream target of pathway ,and then regulate AMPK signaling pathway ,so as to promote glucose uptake of IR-HepG 2 cells,reduce TG and TC contents,and improve IR and abnormal glucose and lipid metabolism.

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