1.Long noncoding RNA MRAK088388 is involved in the progression of childhood allergic asthma via miR-30a/ATG5 axis
Weiwei SHE ; Tianshou SUN ; Chengfeng LONG ; Meiyu CHEN ; Xu CHEN ; Qinxue LIAO ; Mingdong WANG ; Wei CAO
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(5):764-772
【Objective】 To investigate the association between the long-stranded non-coding ribonucleic acid (lncRNA) MRAK088388 and allergic asthma in children. 【Methods】 A total of 15 healthy children and 15 children with asthma were monitored for disease progression over a 2-year period. Blood samples were collected from patients during the chronic phase of the disease for lncRNA/mRNA expression microarray analysis. Competing endogenous RNA networks (MRAK088388/miR-30a/ATG5) were identified by bioinformatics analysis. In vitro cultured bronchial epithelial (16HBE) cells were used to quantify gene and associated protein expression levels by real-time fluorescent quantitative polymerase chain reaction (qPCR) and protein blotting, respectively. Cell Counting Kit-8 and transwell assays were used to assess the proliferation and migration of 16HBE cells and verify the effects of MRAK088388, miR-30a and ATG5 on asthma. 【Results】 Six lncRNA-miRNA-mRNAs were identified by correlation analysis. By qRT-PCR analysis, MRAK088388/miR-30a/ATG5 was selected to construct the ceRNA network in this study. mRAK088388 and ATG5 expressions were high in the peripheral blood of children with asthma, while the expression of miR-30a was low (P<0.05). The expression level of E-cadherin was significantly higher in 16HBE cells after si-MRAK088388+TGF-β1 group, while the expression levels of Vimentin and α-SMA were significantly lower (P<0.05), indicating that knockdown of MRAK088388 inhibited the epithelial mesenchymal transition in 16HBE cells. Compared with si-NC+ TGF-β1 group, the cell morphology of si-MRAK088388+TGF-β1 group was similar to that of the control group, indicating that MRAK088388 knockdown attenuated TGF-β1-induced cell morphological changes; in addition, MRAK088388 knockdown inhibited TGF-β1-induced proliferation and migration of 16HBE cells. MRAK088388 was confirmed by qPCR and protein blotting to promote the progression of childhood asthma by targeting the miR-30a/ATG5 axis. 【Conclusion】 Childhood asthma is associated with the MRAK088388/miR-30a/ATG5 axis, and MRAK088388 is involved in the process of childhood allergic asthma by negatively regulating miR-30a expression and regulating elevated ATG5 expression levels to affect bronchial epithelial cell mesenchymal transition, proliferation, and migration.
2.Inhibition of M2 macrophage polarization and reduction of airway inflammation in asthmatic mice with lncRNA MRAK088388 knockout.
Weiwei SHE ; Tianshou SUN ; Chengfeng LONG ; Meiyu CHEN ; Xu CHEN ; Qinxue LIAO ; Mingdong WANG ; Wei CAO
Chinese Journal of Cellular and Molecular Immunology 2023;39(9):777-786
Objective To investigate the long non-coding RNA(lncRNA) MRAK08838 regulates macrophage function to influence the development of asthmatic airway inflammation. Methods MRAK088388 gene knockout (MRAK088388-/-) mouse model was prepared and allergic asthma was induced by dust mite protein Dermatophagoides farinae 1 (Der f1). The mice were sacrificed after 28 days of modeling, and serum was collected to measure IgE and IgG. The FinePointe RC system was used to measure airway hyperresponsiveness and evaluate lung function in mice. Lung tissue was taken for HE staining, and periodic acid-Schiff (PAS) staining was used to evaluate inflammatory infiltration and mucus secretion in mouse lungs. Fluorescence quantitative PCR was used to detect the expression level of lncRNA MRAK08838 in bronchoalveolar lavage fluid (BALF) cells and lung tissue of asthmatic mice. ELISA was used to detect the levels of inflammatory cytokines IFN-γ, IL-4, IL-5, IL-13, IL-10 and IL-17A. Flow cytometry was used to evaluate the phenotype of macrophages in BALF and lung tissue, as well as the proportion of neutrophils, eosinophils, and alveolar macrophages. The changes of the above indicators were detected in mice by adoptive transfer of bone marrow-derived macrophages (BMDM). Results Under the challengle of Der f1, MRAK088388-/- mice showed reduced allergic airway inflammation, including reduced eosinophils in BALF and reduced production of IgE and IgG1. In addition, Der f1-treated MRAK088388-/- mice had fewer M2 macrophages than wild-type asthmatic mice. Wild-type mouse BMDM (M0) and Der f1-treated MRAK088388-/- mice also showed mild inflammatory response. Conclusion Knockout of MRAK088388 alleviates airway inflammation in asthmatic mice by inhibiting M2 polarization of airway macrophages.
Animals
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Mice
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Mice, Knockout
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RNA, Long Noncoding/genetics*
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Asthma/genetics*
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Macrophages
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Immunoglobulin E
3.Analysis on risk factors for prognosis of traumatic brain injury in adults and establishment of the prediction model
Mingdong BAO ; Junmiao GE ; Qiuzi YANG ; Jidong SUN ; Xiuquan WU ; Xiaofan JIANG ; Peng LUO
Chinese Journal of Trauma 2023;39(3):229-237
Objective:To analyze risk factors for prognosis of adult patients with traumatic brain injury (TBI), construct the prognostic model of TBI and evaluate its predictive value.Methods:A case-control study was used to analyze the clinical data of 522 patients with TBI admitted to Xijing Hospital of Air Force Medical University from March 2011 to September 2019, including 438 males and 84 females; aged 18-75 years [(44.9±15.0)years]. According to the Glasgow outcome score (GOS) at discharge, the patients were divided into good prognosis group (GOS 4-5 points, n=165) and poor prognosis group (GOS 1-3 points, n=357). The two groups were compared with regards to qualitative data such as sex, underlying diseases, causes of injury, multiple injuries, open injuries, intracranial foreign bodies, cerebral herniation, consciousness status on admission and at discharge, surgery, lung infection on admission, tracheostomy, ventilator-assisted ventilation, hospital-acquired pneumonia/pathogenic bacteria and intracranial infection, and quantitative data such as Glasgow coma score (GCS) on admission and at discharge, age, measurements on admission [systolic blood pressure, diastolic blood pressure, mean arterial pressure, temperature, heart rate, creatinine, urea nitrogen, blood sodium, blood potassium, blood glucose, prothrombin time (PT), activated partial thromboplastin time (APTT), platelets, international normalized ratio (INR), pupil size of both eyes] and length of hospital stay. Univariate analysis and Lasso regression analysis were used to screen the risk factors affecting the prognosis of TBI patients, and the selected influencing factors were included in multivariate Logistic regression analysis to identify independent risk factors and construct regression equations. R was used to draw a visual nomogram based on regression equation for predicting the prognosis of TBI patients. The prognostic predictive value of the nomogram was evaluated by using the receiver operating characteristic (ROC) curve, and the area under the curve (AUC), Youden index, sensitivity, specificity and consistency index (C index) were calculated. Results:Univariate analysis showed that there were significant differences between the two groups in underlying diseases, open injuries, cerebral herniation, consciousness status on admission and at discharge, lung infection on admission, tracheostomy, ventilator-assisted ventilation, hospital-acquired pneumonia/pathogenic bacteria, GCS on admission and at discharge, age, and measurements on admission (systolic blood pressure, mean arterial pressure, body temperature, heart rate, creatinine, urea nitrogen, blood potassium, blood glucose, PT, INR, pupil size of right eye) (all P<0.05 or 0.01). There were no significant differences between the two groups in gender, causes of injury, multiple injuries, intracranial foreign bodies, surgery, intracranial infection, measurements on admission (diastolic blood pressure, blood sodium, APTT, platelets, pupil size of left eye) and length of hospital stay (all P>0.05). After screening by Lasso regression model, the results of multivariate Logistic regression analysis showed that GCS on admission ( OR=0.67, 95% CI 0.62, 0.73, P<0.01), age ( OR=1.03, 95% CI 1.01, 1.04, P<0.01), blood glucose on admission ( OR=1.17, 95% CI 1.06, 1.30, P<0.01) and INR on admission ( OR=17.08, 95% CI 2.12, 137.89, P<0.01) could be used as the main risk factors to construct the prediction model, and the regression equation was constructed: Logit [ P/(1- P)]=-0.398× "GCS on admission"+0.024× "age"+0.158×"blood glucose on admission"+2.838×"INR on admission"-1.693. The AUC for the prognosis prediction in adult patients with TBI using R based on a visual nomogram model was 0.87 (95% CI 0.83, 0.89, P<0.01). The Youden index for the predicted probability was 0.60 (sensitivity of 85.2% and specificity of 75.2%), with the C index of 0.87. Conclusion:Age, GCS on admission, blood glucose on admission and INR on admission are the main risk factors affecting the prognosis of TBI in adults, and the nomogram drawn by these parameters can better predict their clinical outcome.
4.Research progress of mesenchymal stem cells in peripheral nerve injury repair
Dedong LI ; Jian SUN ; Mingdong YU ; Bo LI ; Yuechun LU
International Journal of Biomedical Engineering 2020;43(5):382-386
Peripheral nerve injury (PNI) is an important clinical complication, which brings long-term physical and psychological pain and economic burden to patients. There is no satisfactory treatment plan for PNI. Although microsurgery technology has been greatly developed, some peripheral nerve defects or ruptures caused by external forces can be repaired by surgery or nerve transplantation. However, due to the weak ability of nerve cell regeneration and surgical operations may cause damage to the injured nerves, the patient's functional recovery may not be able to achieve the desired effect. Therefore, it is urgent to find a safe and effective method to treat PNI. Mesenchymal stem cells have special differentiation potential and can differentiate into a variety of cell types in vitro and in vivo, and have received widespread attention from researchers. In this paper, the research progress of mesenchymal stem cells in nerve injury repair was summarized, and the characteristics, functions of mesenchymal stem cells and the mechanism of action in peripheral nerve injury repair were reviewed.
5. Plaque features in saphenous vein graft evaluated by virtual histology intravascular ultrasound
Yin LIU ; Zhuang CUI ; Yueying WANG ; Bo SUN ; Jianyong XIAO ; Mingdong GAO ; Jixiang WANG ; Xiaowen GONG ; Siyuan FENG ; Jing GAO
Chinese Journal of Cardiology 2019;47(1):26-33
Objective:
To investigate the features of plaques of saphenous venous graft (SVG) with virtual histology intravascular ultrasound (VH-IVUS) in patients underwent coronary artery bypass graft surgery.
Methods:
From March 2016 to March 2018, a total of 45 patients ((64.4±7.9) years old, 88.9% male (40 cases)) with ischemic symptoms after coronary artery bypass graft surgery and with coronary artery angiography evidenced SVG stenosis greater than or equal to 50%, who received percutaneous coronary intervention in Tianjin chest hospital were continuously included in this study, and the clinical data were retrospectively analyzed. VH-IVUS was performed before PCI to analyze plaque composition. The patients were divided into no smoking group (21 cases) and smoking group (24 cases), no diabetes group (30 cases) and diabetes group (15 cases), normal very low density lipoprotein cholesterin (VLDL-C) group (24 cases) and elevated VLDL-C group (21 cases), stable angina pectoris group (5 cases) and acute coronary syndrome group (40 cases), plaque burden (PB) < 70% group (11 cases) and PB ≥ 70% group (34 cases), without thin-cap fibroatheroma group (35 cases) and thin-cap fibroatheroma group (10 cases), and plaque features were compared between different groups.
Results:
The graft age was (8.9±3.7) years.The stenosis degree of SVG lesions was 90 (90, 98) %. The minimum lumen diameter was 1.6 (1.5, 1.8) mm. The vessel cross-sectional area was (12.1±4.0) mm2. The plaque area was 8.6 (5.7,12.0) mm2. The minimum lumen area was 2.5 (2.1,3.3) mm2. The plaque burden was (75.3±8.3)%. The fibrotic tissue (FI) ratio was (65.1±10.1)%, fibrofatty plaque (FF) ratio was 13.8 (5.4,25.3) %, necrotic core tissue (NC) ratio was 12.0 (5.4,24.0)%, and dense calcium tissue (DC) ratio was1.0 (0.2,3.8)% in SVG lesions. There were no significant differences in SVG plaque area, FI area,FF area,NC area,and DC area between no smoking group and smoking group, no diabetes group and diabetes group, and normal VLDL-C group and elevated VLDL-C group. SVG plaque volume was significantly higher in acute coronary syndrome group than in stable angina pectoris group (262.2 (148.5,401.2) mm3 vs. 93.1 (50.6,155.9) mm3,
6.The diagnosis and treatment of acute myocardial infarction complicated with left ventricular wall rupture:a report of three cases
Mingdong GAO ; Jianyong XIAO ; Yanbo ZHU ; Yongjuan LUO ; Xin GUAN ; Lianqun WANG ; Qing ZHANG ; Yin LIU ; Genyi SUN
Tianjin Medical Journal 2016;44(12):1452-1455
Objective To investigate the diagnosis and treatment in patients with acute myocardial infarction (AMI) and complicated left ventricular wall rupture (LVWR). Methods A retrospective analysis was made on the clinical features, diagnosis and successful treatment in three AMI patients with LVWR from December 2015 to April 2016. Results Three cases were included in this study. Case 1, the mesh like cardiac rupture after AMI was diagnosed by ultrasonic Doppler. Emergency revascularization was performed due to the combined cardiac shock, and the infarct related artery was opened. The vasoactive drugs were used after revascularization to reduce ventricular pressure load and volume load in the haemodynamic monitoring, and anticoagulation, antiplatelet agents were less used or discontinued to promote local thrombus healing of ventricular rupture. Case 2 was a recurrent myocardial infarction patient. LVWR was diagnosed by ultrasonic Doppler one day after emergency operation. The ruptured ventricular wall was encapsulated by thrombus. The drug therapy was effective in hemodynamic monitoring. LVWR was further confirmed by cardiac CT after clinical stabilization. Case 3 was diagnosed LVWR by ultrasonic Doppler four days after AMI. Because the ruptured ventricular wall was limited by incompletely organized thrombus, and the haemodynamic condition was stable, selective surgical repair of rupture after coronary angiography was performed. Conclusion The effective drug therapy combined with percutaneous coronary intervention and surgical repair can reduce the risk of death in patients with LVWR after AMI.
7.The application of particle concentration or mass concentration of lipoprotein (a) in the evaluation of coronary artery plaques characteristics
Lishan SUN ; Liu LU ; Mingdong WANG ; Cuncun CHEN ; Qian WANG ; Lieying FAN
Chinese Journal of Laboratory Medicine 2016;39(3):215-219
Objective To investigate the clinical value of serum lipoprotein ( a ) concentration in evaluation of plaques characteristics for patients with coronary atherosclerotic heart diseases ( CAHD ) . Methods Using case-control method, Patients with suspicious CAHD, received coronary computed tomography angiography in the Shanghai East Hospital during October 2013 to June 2015 were enrolled.According to the results of coronary artery CTA, the patients were divided into two groups : the CAHD group (352 cases) and control group(438 cases) , the particle concentrations and mass concentration of lipoprotein(a), triglyceride, total cholesterol, HDL-C, LDL-C, glucose, HBA1c and hs-CRP and other tests were measured, the patients of CAHD group were divided into three subgroups by characteristics of coronary artery plaques including soft plaque (176 cases), calcified plaque (90 cases) and mixed plaque (86 cases), analysis were made with all these data.Using T test or variance analysis to compare the means between or among groups, the risk for CAHD was analyzed by logistic regression, the relationship between LP (a) -P and LP( a) -M were explored by linearly egression analysis, Conformance test were analyzed using kappa test.Results Compared with control group, the mean results of the CAHD group are significantly higher than that of control group, including LP (a) -P 18.5(8.3 -43.0))nmol/L vs.13.6 (7.6-32.4)nmol/L( t =-2.110), LP(a)-M 183(71 -361)mg/L vs.126(67 -293)mg/L(t =-2.063), age (62 ±9)years vs.(52 ±9)years(t=-7.691), hs-CRP 0.86(0.44-1.97) )mg/L vs.0.70(0.38-1.64)mg/L(t=-2.236), glucose (6.1 ±2.29 )mmol/L vs.(5.36 ±1.32 )mmol/L(t=-4.914), BA1c (6.13 ±0.98) % vs.(5.81 ±0.58) %(t=-4.842), APO(B) (1.09 ±0.33) g/L vs.(1.03 ±0.29) g/L( t=-2.407), all of the P values <0.05;The relative risk(RR)of age, glucose, LP( a)-P and LP ( a)-M are 1.067, 2.377, 1.384 and 1.342 respectively; Among the three types of plaques groups,the mean differences of age, TC, HDL-C, LDL-C and LP ( a)-P are statistically significant ( F=6.276,3.060,3.127,4.723,2.878;all of the P<0.05);The median of LP ( a)-P in the soft plaque group 20.3(8.3-48.2)nmol/L is higher than that of the mixed plaque group 15.7(7.3-26.0)nmol/L(P<0.05 ) and calcified plaque group 15.6 ( 8.1 -23.1 ) nmol/L ( P <0.05 ).The linearly regression equation of LP ( a) -M and LP( a)-P is Y=6.646X, r=0.939; Consistency test indicate the two methods are not consistent when used for grouping ( Kappa value is 0.557 ).Conclusions Serum concentration of lipoprotein(a) is an independent risk factor of CAHD, and the particle concentration of LP(a) is closely related to the characteristics of the plaques, especially to the soft plaque.
8.Clinical significance of detecting glucagon like peptide-1 in late-onset Alzheimer′s disease
Mingdong WANG ; Lishan SUN ; Ming ZONG ; Liu LU ; Lin LU ; Lieying FAN
Chinese Journal of Laboratory Medicine 2015;(8):543-547
Objective To explore the serum level of Glucagon like peptide-1 in late-onset Alzheimer′s patients and its clinical significance.Methods Case control study.Collecting cerebral vascular disease fifty-five cases, diagnosed with late-onset Alzheimer′s disease sixty-one cases, type 2 diabetes mellitus fifty-one cases , type 2 diabetic patients combined with late-onset Alzheimer′s disease thirty-seven patients from the Shanghai East Hospital and partly Pudong area elderdly hospital during October 2013 to March 2014, and forty healthy persons as normal control from physical examination center of Shanghai East Hospital during September 2013 to February 2014.Measuring the concentrations of GLP-1,β-amyloid, Tau protein and other routinely used clinical tests in the serum of patients from the normal controls , cerebrovascular disease , late-onset Alzheimer′s disease, type 2 diabetes and type 2 diabetes mellitus combined with late-onset Alzheimer′s disease by ELISA method developed in our laboratory.The blood samples were also collected at three fixed time including fasting time ,1 hour after taking glucose , 2 hour after taking glucose, the concentrations of GLP-1 were determined in the LOAD group , T2DM group and the T2DM combined with LOAD group and normal control group.The concentrations of serum GLP-1 among groups were compared with single factor analysis of variance , and the concentrations of serum GLP-1 between the two groups were compared using LSD-t test.Analysing the correlation between GLP-1 and other indicators with Pearson analysis.Results The fasting GLP-1 levels of LOAD group were ( 123.4 ±20.8 ) nmol/L, and they were highest between the normal control group (78.6 ±6.0) nmol/L and the cerebral blood vessel disease group(89.0 ±8.7)nmol/L (F values were 3.46 and 1.98, P<0.05).The fasting GLP-1 levels of T2DM combined with LOAD group (157.9 ±28.6) nmol/L were higher than the LOAD group (123.4 ± 20.8) nmol/L (t =1.63,P <0.05), but there were no difference of the fasting GLP-1 levels between T2DM combined with LOAD group (157.9 ±28.6) nmol/L and T2DM group(153.8 ±18.0)nmol/L(t=0.96,P>0.05).Deficient secretion of GLP-1 after taking glucose 1 hour in most of the patients of T2DM combined with LOAD group (99.1 ±14.2) nmol/L, LOAD group(73.9 ±6.6 ) nmol/L and T2DM group (96.3 ±7.0 ) nmol/L could be concluded .The GLP-1 levels of T2DM combined with LOAD group after taking sugar 2 hour were (115.4 ±18.6)nmol/L ,and were higher than that of normal levels (63.3 ±6.2) nmol/L after taking sugar 2 hour(t=4.49,P<0.05).There were no difference between the GLP-1 levels of the LOAD group (73.6 ±5.8 )nmol/L and the GLP-1 levels of the normal group(63.3 ±6.2)nmol/L after taking sugar 2 hour (t=0.94,P>0.05).Pearson correlation analysis showed that the relationship of the levels of GLP-1 with Aβ( 1-42 ) and the levels of GLP-1 after taking glucose 1 h and 2 h were positively relative, and its coefficients of correlation were 0.401,0.436,0.722.Conclusions LOAD and T2MD are similar, and they have GLP-1 secretion shortage phenomenon after taking glucose , so monitoring dynamic change of GLP-1 after taking glucose may contribute to the auxiliary diagnosis of LOAD.
9.Comparing the estimated glomerular filtration rate through different equations in evaluating kidney function of the population
Lishan SUN ; Liu LU ; Mingdong WANG ; Lin LU ; Ming YU ; Lieying FAN
International Journal of Laboratory Medicine 2015;(10):1370-1372,1375
Objective To compare the difference of kidney function evaluated by using 3 different estimated glomerular filtration rate(GFR) equations in populations .Methods Retrospectively analyzed 65 856 patients who measured serum creatinine and Cysta‐tin C at the same time ,and come from the outpatients or inpatients of the hospital .The estimated GFR (eGFR) were calculated through 3 equations ,then compared the eGFR in the population and among different groups according to different kidney functions , and then grouped the people enrolled in the study again according to the eGFR calculated by using the 3 different equations and compared the differences among groups .Results Compared with the eGFR calculated by using Creatinine equation ,the correlation coefficients of the eGFRs calculated by using the other two equations were 0 .81 and 0 .90 ,respectively ,both P<0 .05 ;The differ‐ence between the means of eGFR were 6 .19 and 1 .79 mL/(min × 1 .73 m2 ) respectively with obvious significance (P<0 .01) ,in consistency analysis .There were obvious overestimation of kidney function when using Creatinine equation to calculate eGFR .Con‐clusion There is consistence and obvious difference by using the 3 CKD‐EPI′s eGFR equations .Physicians should choose suitable equations to evaluate kidney function in different populations .
10.Modified FOLFOX4 vs docetaxel-oxaliplatin program neoadjuvant chemotherapy in postoperative stage Ⅲ gastric cancer
Haibo YE ; Weijian SUN ; Mingdong LU ; Shuai LIU ; Ke CHEN ; Jingwei HU ; Zhiqiang ZHENG
Chinese Journal of General Surgery 2014;29(6):429-432
Objective To compare the efficacy and safety of modified FOLFOX4 program with docetaxel-oxaliplatin-5-fluorouracil (DOF) program as neoadjuvant chemotherapy in stage Ⅲ gastric cancer patients.Methods In 86 cases of stage Ⅲ gastric cancer patients,42 received modified FOLFOX4 chemotherapy,44 cases were treated by DOF program.After two cycles of chemotherapy,the treatment effect and adverse reactions were evaluated.Results The total effectiveness in modified FOLFOX4 group and DOF group was 60% (25/42) and 68% (30/44) respectively (P > 0.05).Tumor control rate was 83% (35/42) and 89% (39/44) respectively (P > 0.05).The incidence of nausea,vomiting and leukopenia was higher in DOF group than modified FOLFOX4 group (P < 0.05).The D2 lymph node dissection rate between modified FOLFOX4 group and DOF group was 80% (20/25) and 87% (26/30) respectively (P > 0.05),the R0 resection rate was 72% (18/25) and 83% (25/30) respectively (P > 0.05).In 43 R0 resection patients using FOLFOX4 the median survival time was 38.7 months,1-,3-year survival rate was 90%,and 60% ; while that in DOF group the median survival time was 39.6 months,1-,3-year survival rate was 95%,and 75%.Multivariate analysis showed that postoperative TNM stage only was an independent risk factor for prognosis.Conclusions TNM stage was the independent risk factor for prognosis of gastric carcinoma patients after radical gastrectomy.

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