1.Effects of melezitose on ulcerative colitis mice
Zhang-Hao CHEN ; Shuang GAO ; Jin-Fa LI ; Zhen GAN ; Jun-Min CHANG
The Chinese Journal of Clinical Pharmacology 2024;40(14):2083-2087
		                        		
		                        			
		                        			Objective To investigate the mechanism of melezitose(MELE)on ulcerative colitis(UC)by structing a mouse model of ulcerative colitis(UC)induced by dextran sodium sulfate(DSS).Methods Forty-eight SPF grade male c57BL/6 mice were randomly divided into normal group(0.9%NaCl),model group(0.9%NaCl),control group(100 mg·kg-1 mesalazine)and experimental-L,-M,-H groups(20,40,80 mg·kg-1 melezitose solution).The UC model was induced by giving 3%DSS solution instead of drinking water,and the disease activity index(DAI)was evaluated.Serum levels of interleukin-1 β(IL-113),IL-6,IL-10 and tumor necrosis factor α(TNF-α)were detected by enzyme linked immunosorbent assay.The expression levels of major histocompatibility complex Ⅱ(MHC Ⅱ)and cluster of differentiation 4 receptors(CD4)protein were detected by Western blot.Results The levels of IL-1 β in serum in the experimental-M,-H groups,model group and normal group were(82.15±13.66),(75.56±11.07),(118.20±19.31)and(23.47±4.72)pg·mL-1;serum IL-6 levels were(71.54±16.48),(58.57±15.62),(140.60±5.76)and(30.33±4.15)pg·mL-1;serum IL-10 levels were(48.64±5.60),(52.65±7.99),(27.10±4.91)and(61.90±10.44)pg·mL-1;serum TNF-α levels were(70.33±8.51),(66.55±8.12),(90.88±4.90)and(34.18±4.15)pg·mL-1;the relative expression levels of MHC Ⅱ protein were 0.34±0.04,0.15±0.06,0.08±0.05 and 0.53±0.59;the relative expression levels of CD4 protein were 0.79±0.08,0.92±0.12,0.99±0.11 and 0.54±0.14,respectively.Compared with the model group,the above indexes in the experimental-M,-H groups showed statistically significant differences(P<0.05,P<0.01).Conclusion Melezitose could effectively improve the symptoms of UC mice;the mechanism may be through down-regulating MHC Ⅱ protein and up-regulating CD4 protein to activate T cell signal pathway to play an anti-inflammatory effect.
		                        		
		                        		
		                        		
		                        	
2.Dahuang Lingxian Prescription Regulates Effect of TAK1 and TRAF6 Interaction and Co-localization on Inflammatory Response of Bile Duct Cells
Yi-rong GAN ; Xiong-bin GUI ; Yuan YU ; Bin XU ; Jian-ye DAI ; Ming CHANG ; Jin-mei CHEN ; Cheng-ji LI
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(6):92-99
		                        		
		                        			
		                        			ObjectiveTo observe the repair effect of Dahuanglingxian prescription (DHLX) on bile duct epithelial cells of rats. To explore whether its mechanism of action is to adjust the mutual binding of transforming growth factor -β (TGF-β) activated kinase 1(TAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6), and regulate the activation of the nuclear transcription factor -κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway. MethodThe 20 SD rats were randomly divided into normal group and DHLX group, 10 rats in each group, were given saline and DHLX (320 mg·kg-1·d-1) for 8 days, to prepare normal serum and DHLX serum. Biliary epithelial cells were extracted from normal SD rats and divided into 9 groups: Normal group, model group (20 mg·L-1), LPS+DHLX group (20 mg·L-1+10% DHLX), LPS+PDTC group (20 mg·L-1+200 μmol·L-1), LPS+SB203580 group (20 mg·L-1+0.5 μmol·L-1), LPS+PDTC+SB203580 group (20 mg·L-1+200 μmol·L-1+0.5 μmol·L-1), LPS+PDTC+DHLX group (20 mg·L-1+200 μmol·L-1+10% DHLX serum), LPS+SB203580+DHLX group (20 mg·L-1+0.5 μmol·L-1+10% DHLX serum), LPS+PDTC+SB203580 +DHLX group (20 mg·L-1+200 μmol·L-1+0.5 μmol·L-1+10% DHLX serum). The microscopic observation of morphological changes in each group of cells after drug intervention. Enzyme-linked immunosorbent assay(ELISA) was used to detect the expression of (IL)-1β and IL-6 in each group of cells. Western blot detected the expression levels of TAK1 and TRAF6 proteins in each group of cells, Co-IP detected the interaction between TAK1 and TRAF6, and further observed the distribution and co-localization of TAK1 and TRAF6 using Laser confocal microscope. ResultAfter the action of LPS, the cell synapses are reduced, the cell body becomes significantly rounded and smaller, but the cell morphology of each group tends to be normal after medication. Compared with normal group, the expression levels of IL-1β and IL-6 in model group were significantly increased (P<0.05), while the expression level of TAK1 was decreased while the expression level of TRAF6 was increased (P<0.05). The content of TAK1-TRAF6 protein complex showed a decreasing trend, and the two proteins co-located in the cytoplasm. Compared with model group, the expression levels of IL-1β and IL-6 in LPS+DHLX group were significantly decreased (P<0.05), the expression level of TAK1 was increased and the expression level of TRAF6 was decreased (P<0.05), the content of TAK1-TRAF6 protein complex was significantly increased (P<0.01), and the two proteins were significantly co-located in cytoplasm. Compared with LPS+DHLX group, the expression levels of IL-1β and IL-6 in other groups were significantly decreased (P<0.05,P<0.01). TAK1-TRAF6 protein complex content in each group was significantly decreased after pathway blocker intervention (P<0.05), while TAK1-TRAF6 protein complex content in each group was significantly increased after pathway blocker combined with DHLX intervention (P<0.05). Co-localization of the TAK1-TRAF6 in cytoplasm was not obvious. ConclusionIn the LPS-induced inflammatory response of bile duct cells, the binding of TAK1 and TRAF6 showed a weakening trend, but DHLX could reverse the phenomenon, we think the mechanism of action may be related to promoting the mutual binding of TAK1 and TARF6 to inhibit the activation of the NF-κB/MAPK signaling pathway. 
		                        		
		                        		
		                        		
		                        	
3.Deep learning applied to two-dimensional color Doppler flow imaging ultrasound images significantly improves diagnostic performance in the classification of breast masses: a multicenter study.
Teng-Fei YU ; Wen HE ; Cong-Gui GAN ; Ming-Chang ZHAO ; Qiang ZHU ; Wei ZHANG ; Hui WANG ; Yu-Kun LUO ; Fang NIE ; Li-Jun YUAN ; Yong WANG ; Yan-Li GUO ; Jian-Jun YUAN ; Li-Tao RUAN ; Yi-Cheng WANG ; Rui-Fang ZHANG ; Hong-Xia ZHANG ; Bin NING ; Hai-Man SONG ; Shuai ZHENG ; Yi LI ; Yang GUANG
Chinese Medical Journal 2021;134(4):415-424
		                        		
		                        			BACKGROUND:
		                        			The current deep learning diagnosis of breast masses is mainly reflected by the diagnosis of benign and malignant lesions. In China, breast masses are divided into four categories according to the treatment method: inflammatory masses, adenosis, benign tumors, and malignant tumors. These categorizations are important for guiding clinical treatment. In this study, we aimed to develop a convolutional neural network (CNN) for classification of these four breast mass types using ultrasound (US) images.
		                        		
		                        			METHODS:
		                        			Taking breast biopsy or pathological examinations as the reference standard, CNNs were used to establish models for the four-way classification of 3623 breast cancer patients from 13 centers. The patients were randomly divided into training and test groups (n = 1810 vs. n = 1813). Separate models were created for two-dimensional (2D) images only, 2D and color Doppler flow imaging (2D-CDFI), and 2D-CDFI and pulsed wave Doppler (2D-CDFI-PW) images. The performance of these three models was compared using sensitivity, specificity, area under receiver operating characteristic curve (AUC), positive (PPV) and negative predictive values (NPV), positive (LR+) and negative likelihood ratios (LR-), and the performance of the 2D model was further compared between masses of different sizes with above statistical indicators, between images from different hospitals with AUC, and with the performance of 37 radiologists.
		                        		
		                        			RESULTS:
		                        			The accuracies of the 2D, 2D-CDFI, and 2D-CDFI-PW models on the test set were 87.9%, 89.2%, and 88.7%, respectively. The AUCs for classification of benign tumors, malignant tumors, inflammatory masses, and adenosis were 0.90, 0.91, 0.90, and 0.89, respectively (95% confidence intervals [CIs], 0.87-0.91, 0.89-0.92, 0.87-0.91, and 0.86-0.90). The 2D-CDFI model showed better accuracy (89.2%) on the test set than the 2D (87.9%) and 2D-CDFI-PW (88.7%) models. The 2D model showed accuracy of 81.7% on breast masses ≤1 cm and 82.3% on breast masses >1 cm; there was a significant difference between the two groups (P < 0.001). The accuracy of the CNN classifications for the test set (89.2%) was significantly higher than that of all the radiologists (30%).
		                        		
		                        			CONCLUSIONS:
		                        			The CNN may have high accuracy for classification of US images of breast masses and perform significantly better than human radiologists.
		                        		
		                        			TRIAL REGISTRATION
		                        			Chictr.org, ChiCTR1900021375; http://www.chictr.org.cn/showproj.aspx?proj=33139.
		                        		
		                        		
		                        		
		                        			Area Under Curve
		                        			;
		                        		
		                        			Breast/diagnostic imaging*
		                        			;
		                        		
		                        			Breast Neoplasms/diagnostic imaging*
		                        			;
		                        		
		                        			China
		                        			;
		                        		
		                        			Deep Learning
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			ROC Curve
		                        			;
		                        		
		                        			Sensitivity and Specificity
		                        			
		                        		
		                        	
4.A new phenylethanol glycoside from Baphicacanthis Cusiae Rhizoma et Radix.
Fan XU ; Chang-Xin ZHOU ; Jian-Xia MO ; Li-She GAN
China Journal of Chinese Materia Medica 2021;46(18):4749-4756
		                        		
		                        			
		                        			The 95% ethanol extract of Baphicacanthis Cusiae Rhizoma et Radix was purified by multi-chromatographic methods including microporous resin, silica gel, Sephadex LH-20, and C_(18) reversed-phase column chromatography. Fourteen compounds were isolated and structurally identified, including five phenylethanoid glycosides, five phenylpropanoids, one lupinane triterpene, two alkaloids, and one flavonoid, listed as follows: 2-(4-hydroxy-3-methoxyphenyl)-3-(2-hydroxy-5-methoxyphenyl)-3-oxo-1-propanol B(1), threo-2,3-bis-(4-hydroxy-3-methoxybenzene)-3-methoxypropanol(2), 2-(3-hydroxy-4-methoxyphenyl)-ethanol-1-O-[3,4-O-di-acetyl-(1→3)-O-α-L-rhamnopyranosyl]-β-D-glucopyranoside(3), verbascoside(4), 2″,3″-di-O-acetyl martynoside(5),(+)-pinore-sinol(6), diospyrosin(7), daidzein(8), wiedemannioside B(9), buddlenol A(10), 2″-O-acetyl martyonside(11), lupeol(12), indirubin(13), and tryptanthrin(14). Compound 3 was a new phenylethanoid glycoside, and the other 10 compounds were isolated for the first time from Baphicacanthis Cusiae Rhizoma et Radix except compounds 12, 13, and 14.
		                        		
		                        		
		                        		
		                        			Cardiac Glycosides
		                        			;
		                        		
		                        			Flavonoids
		                        			;
		                        		
		                        			Glycosides
		                        			;
		                        		
		                        			Molecular Structure
		                        			;
		                        		
		                        			Phenylethyl Alcohol
		                        			;
		                        		
		                        			Rhizome
		                        			
		                        		
		                        	
5.Analysis on influencing factors for nonalcoholic fatty liver disease in Jinchang cohort
Yanbei HUO ; Yana BAI ; Desheng ZHANG ; Xiaoyu CHANG ; Chun YIN ; Yupei BA ; Yufeng WANG ; Ting GAN ; Jiao DING ; Na LI ; Wenling ZHANG ; Ning CHENG
Chinese Journal of Epidemiology 2021;42(3):493-498
		                        		
		                        			
		                        			Objective:To explore the influencing factors for non-alcoholic fatty liver disease (NAFLD) in Jinchang cohort, and provide scientific basis for the prevention and control of NAFLD.Methods:A total of 20 051 patients without fatty liver at baseline survey and met the inclusion criteria in Jinchang cohort were selected as study subjects. Prospective cohort study and Cox regression analysis were used to investigate the influencing factors for NAFLD, and the dose-response relationship between related biochemical indicators and NAFLD risk was studied by restricted cubic spline method.Results:The incidence of NAFLD was 42.37/1 000 person years. Multivariate Cox regression analysis showed that being worker and technical personnel (being worker: HR=0.84,95% CI:0.70-0.99;being technical personnel: HR=0.73,95% CI:0.56-0.95), tea drinking (current drinking: HR=0.86,95% CI:0.78-0.94;previous drinking: HR=0.52,95% CI: 0.31-0.86), exercise (occasionally: HR=0.79, 95% CI: 0.68-0.91;frequently: HR=0.60,95% CI:0.52-0.69), low body weight ( HR=0.10, 95% CI: 0.05-0.22), daily intake of dairy products >300 ml/day ( HR=0.78, 95% CI: 0.71-0.87) and HBV infection ( HR=0.77, 95% CI: 0.60-0.99) were the protective factors for NAFLD, while being internal or office workers ( HR=1.84, 95% CI: 1.46-2.31), income ≥2 000 yuan (2 000- yuan: HR=1.32, 95% CI: 1.04-1.66; ≥5 000 yuan: HR=1.72, 95% CI:1.11-2.66), bachelor degree or above ( HR=1.35,95% CI:1.03-1.76), overweight ( HR=2.31, 95% CI:2.08-2.55), obesity ( HR=3.95, 95% CI: 3.42-4.56), impaired fasting blood glucose ( HR=1.31, 95% CI:1.17-1.47), diabetes ( HR=1.53, 95% CI: 1.30-1.80), increased TC ( HR=1.37,95% CI:1.24-1.52), increased TG ( HR=1.79,95% CI: 1.62-1.98), decreased HDL-C ( HR=1.29, 95% CI: 1.14-1.45), increased ALT ( HR=1.13, 95% CI: 1.01-1.26) and high-fat diet ( HR=1.24, 95% CI: 1.11-1.40) were the risk factors for NAFLD. Moreover, TC, TG, HDL-C, ALT and FPG all showed good dose-response relationship with the incidence of NAFLD. Conclusion:Occupation, education level, income level, tea drinking, exercise, BMI, FPG, blood lipid, ALT, HBV infection and diet were related to the incidence of NAFLD.
		                        		
		                        		
		                        		
		                        	
6.Elevated serum Dickkopf-1 is a biomarker for bone erosion in patients with psoriatic arthritis
Chung YUKCHIU ; Li ZHI-CHANG ; Sun XIAO-LIN ; Liu YAN-YING ; Shao MIAO ; Gan YU-ZHOU ; Li YI-MIN ; Li YU-HUI ; Zhang XUE-WU
Chinese Medical Journal 2021;134(21):2583-2588
		                        		
		                        			
		                        			Background::Psoriatic arthritis (PsA) is an inflammatory arthropathy characterized by psoriasis and bone erosion on radiology. Dickkopf-1 (Dkk-1) is considered to be the main inhibitor of the Wnt signaling pathway and results in reduced osteoblast proliferation. The aim of this study was to investigate the serum level of Dkk-1 and its association with bone erosion in PsA patients.Methods::Serum Dkk-1 levels were measured by enzyme-linked immunosorbent assay (ELISA) in 69 patients with PsA and 60 controls, including 39 rheumatoid arthritis (RA) patients, and 21 healthy controls (HCs). Rheumatoid factor and anti-cyclic citrullinated peptide levels were also determined by ELISA. The association of Dkk-1 level with clinical and laboratory features of PsA was analyzed. Logistic regression analysis was used to analyze the risk factors for bone erosion in PsA.Results::Dkk-1 was elevated in 68.1% (47/69) of the patients with PsA, 46.2% (18/39) of RA patients, and 9.5% (2/21) of HCs. Serum Dkk-1 concentration was significantly higher in PsA patients compared with that in HCs. The level of serum Dkk-1 was correlated with a swollen joint count, and levels of complement components 3 and 4. Elevated Dkk-1 level (odds ratio = 4.440, 95% confidence interval: 1.246-15.817, P = 0.021) was identified as the risk factor for bone erosion in PsA. Conclusions::The serum level of Dkk-1 is abnormally elevated in PsA patients. The elevation of Dkk-1 might be involved in the mechanism of bone erosion in patients with PsA.
		                        		
		                        		
		                        		
		                        	
7.Comparison of the efficacy of domestic and imported caffeine citrate in the treatment of apnea in preterm infants: a prospective randomized double-blind controlled trial.
Ting HE ; Zheng-Chang LIAO ; Ying DING ; Ming-Jie WANG ; Wen LI ; Ji-Min GAN ; Shao-Jie YUE
Chinese Journal of Contemporary Pediatrics 2020;22(7):684-689
		                        		
		                        			OBJECTIVE:
		                        			To compare the efficacy of domestic and imported caffeine citrate in the treatment of apnea in preterm infants.
		                        		
		                        			METHODS:
		                        			A total of 98 preterm infants with a gestational age of 28 - <34 weeks between April 2018 and December 2019 were enrolled. They were randomly administered with domestic (n=48) or imported caffeine citrate (n=50) within 6 hours after birth. The therapeutic effects, complications, adverse effects and clinical outcomes were compared between the two groups.
		                        		
		                        			RESULTS:
		                        			There were no significant differences in the incidence of apnea within 7 days after birth, daily frequency of apnea, the time of apnea disappearance, the failure rate of intubation-surfactant-extubation strategy, the time of non-invasive assisted ventilation, the duration of oxygen therapy, the duration of caffeine citrate therapy, the length of hospital stay, blood gas analysis results, liver and kidney function testing results between the two groups (P>0.05). There were no significant differences in the incidence of complications and the mortality rate between the two groups (P>0.05). There was no significant difference in the incidence of adverse effects between the two groups (P>0.05).
		                        		
		                        			CONCLUSIONS
		                        			The efficacy and safety of domestic caffeine citrate in the treatment of apnea are similar to those of imported caffeine citrate in preterm infants.
		                        		
		                        		
		                        		
		                        			Apnea
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			Caffeine
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Citrates
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Double-Blind Method
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Infant
		                        			;
		                        		
		                        			Infant, Newborn
		                        			;
		                        		
		                        			Infant, Premature
		                        			;
		                        		
		                        			Infant, Premature, Diseases
		                        			;
		                        		
		                        			Prospective Studies
		                        			
		                        		
		                        	
8.The value of miR-155 and SOCS6 in differentiating tuberculosis infection status
Fake LI ; Jie LUO ; Delu GAN ; Kai CHANG ; Ming CHEN
Chinese Journal of Laboratory Medicine 2020;43(7):751-757
		                        		
		                        			
		                        			Objective:To reveal the significance of microRNA 155 (miR-155) level or the suppressor of cytokine signaling 6 (SOCS6) level in distinguishing the differentiating tuberculosis (TB) infection.Methods:A case-control study was conducted. A total of 60 patients were enrolled in the study retrospectively, including 20 patients with active pulmonary tuberculosis, 20 patients with latent tuberculosis and 20 patients with other pulmonary infectious diseases (non-TB infection), who visited The Third Affiliated Hospital of Third Military Medical University from January to June of 2017. The expression level of miR-155 and SOCS6 in peripheral blood mononuclear cells (PBMC) of from these patients were examined by using the quantitative real-time polymerase chain reaction (qPCR) methods. The associated statistics and graphs was utilized to obtain the relationship, which were reflected by the Co-index receiver operating characteristic(ROC) curve or calculating the area under ROC curve (AUC), between the miR-155 and SOCS6 in differentiating tuberculosis infection by using the Logistic Regressive analysis methods, MedCalc and GraphPad Prism 8.0 software.Results:Neither of the three index miR-155 (AUC=0.663, P=0.031), SOCS6 (AUC=0.708, P=0.002) and Co-index (AUC=0.718, P=0.001) was outstanding to distinguish the tuberculosis infection and non-TB infection. Moreover, the miR-155 (AUC=0.867, P<0.001) and Co-index (AUC=0.875, P<0.001) were similar sufficient ( Z=0.142, P=0.887) to distinguish the active and latent infections. The Co-index (AUC=0.923, P<0.001) was better ( Z=2.586, P=0.010) than SOCS6 (AUC=0.723, P=0.007), and similar ( Z=1.585, P=0.113) to miR-155 (AUC=0.835, P<0.001) on the distinguishing active and non-TB infection. Conclusions:By performing the qPCR and the correlation-analysis, miR-155 has been considered as a potential biomarker for differentiating latent tuberculosis infection from active tuberculosis infection. Conjoint analysis of miR-155 and SOCS6 benefits the distinguishing active TB infection from other pulmonary infectious diseases.
		                        		
		                        		
		                        		
		                        	
9. Analysis on the heritability of diabetes, based on data from the Chinese adult twins
Fengxia GAN ; Wenjing GAO ; Jun LYU ; Canqing YU ; Shengfeng WANG ; Zengchang PANG ; Liming CONG ; Zhong DONG ; Fan WU ; Hua WANG ; Xianping WU ; Guohong JIANG ; Xiaojie WANG ; Binyou WANG ; Zheng CHANG ; Ralf KUJA-HALKOLA ; Weihua CAO ; Liming LI
Chinese Journal of Epidemiology 2019;40(4):389-393
		                        		
		                        			 Objective:
		                        			To analyze the heritability of diabetes among the Chinese twin adults.
		                        		
		                        			Methods:
		                        			A total of 10 253 same-sex twin pairs aged 25 years and older, were selected from the Chinese National Twin Registry (CNTR) program. Heritability of diabetes was calculated by using the structural equation model.
		                        		
		                        			Results:
		                        			After adjusted for age and gender, the overall heritability rates of diabetes were 0.41 (0.15-0.75), 0.83 (0.72-0.91) and 0.34 (0.04-0.73) in the <45 and ≥45 years twin pairs, respectively. After adjusted for age, rates of heritability appeared as 0.37 (0.05-0.78) and 0.88 (0.79-0.94) in men and women, respectively.
		                        		
		                        			Conclusions
		                        			Diabetes is affected by both genetic and environmental factors. The genetic effect of diabetes seemed stronger on female than that on male twins but was dying down along with ageing. 
		                        		
		                        		
		                        		
		                        	
10.A new spirocyclic cycloartane triterpenoid from Souliea vaginata.
Si-Yan ZHANG ; Zhu-Jun FANG ; Yan-Lan WANG ; Chang-Xin ZHOU ; Jian-Xia MO ; Li-She GAN
China Journal of Chinese Materia Medica 2019;44(20):4476-4480
		                        		
		                        			
		                        			The 70% ethanol extract of the whole plant of Souliea vaginata was purified by multi-chromatographic methods including macroporous resin,silica gel,Sephadex LH-20,and C18-reversed-phase column chromatography. A new spirocyclic cycloartane triterpenoid was isolated and identified as( 16 R*,20 R*,23 S*,24 R*,25 S*)-16,23: 23,26-diepoxy-15α,24,25-trihydroxy-9,19-cycloart-3β-O-β-D-xylopyranoside( 1),and named as soulieoside S. Its planar structure and relative configuration were determined by spectroscopic techniques including 2 D NMR and HRESI-MS. As one of the main components of S. vaginata,compound 1 was evaluated for its anti-inflammatory activity by a lipopolysaccharide( LPS)-stimulated NO production model in RAW264. 7 macrophages,but it didn't show NO production inhibitory effect.
		                        		
		                        		
		                        		
		                        			Actaea/metabolism*
		                        			;
		                        		
		                        			Glycosides
		                        			;
		                        		
		                        			Lipopolysaccharides
		                        			;
		                        		
		                        			Molecular Structure
		                        			;
		                        		
		                        			Triterpenes/metabolism*
		                        			
		                        		
		                        	
            
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