1.Relationship of physical activity and screen time with overweight and obesity among children and adolescents with special needs in Tianjin
HAN Yu, LI Zhi, LI Penghong, CUI Tingkai, XIONG Wenjuan, QU Zhiyi, XI Wei, ZHANG Xin
Chinese Journal of School Health 2025;46(2):162-166
		                        		
		                        			Objective:
		                        			To investigate the association of physical activity and screen time with overweight and obesity among children and adolescents with special needs in Tianjin, so as to provide scientific evidence for childhood obesity prevention and intervention measures in the population.
		                        		
		                        			Methods:
		                        			From January 2022 to June 2024, 296 children and adolescents with intellectual disabilities and autism spectrum disorders aged 2-18 years were recruited from special education schools and institutions in Tianjin. Height and weight were measured, and a standardized questionnaire was used to assess physical activity and screen time. Binary Logistic regression analysis was carried out to investigate the association of physical activity and screen time with overweight and obesity.
		                        		
		                        			Results:
		                        			The prevalence of overweight and obesity among children and adolescents with special needs in Tianjin were 17.2% and 21.6%, respectively, and the combined prevalence of overweight and obesity was 38.9%. The median of moderatetovigorous physical activity (MVPA) time was 0.20 h/d, and physical activity sufficiency rate was 7.8%. The median of screen time was 1.79 h/d, and the screen time compliance rate was 68.2%. The binary Logistic regression results showed that lower levels of MVPA time and increased screen time were associated with a higher risk of overweight and obesity among children and adolescents with special needs [OR(95%CI)=1.80(1.06-3.07), 2.40(1.42-4.07),P<0.05].
		                        		
		                        			Conclusions
		                        			Insufficient physical activity and excessive screen time are associated with an increased risk of overweight and obesity among children and adolescents with special needs. Therefore, comprehensive intervention measures should be implemented as early as possible to prevent and reduce the incidence of overweight and obesity in this population.
		                        		
		                        		
		                        		
		                        	
2.Association between Mediterranean diet scores and dental caries among children and adolescents with neurodevelopmental disorders
XIONG Wenjuan, SU Yuanyuan, LIU Zhao, HUANG Xiaoqing, QU Zhiyi, CUI Shanshan
Chinese Journal of School Health 2025;46(2):172-176
		                        		
		                        			Objective:
		                        			To explore the association between mediterranean diet (MD) patterns and dental caries among children and adolescents with neurodevelopmental disorders (NDD), so as to provide a basis for developing scientific anti caries strategies related to diet.
		                        		
		                        			Methods:
		                        			From December 2021 to June 2024, a questionnaire survey, a three day 24 hour dietary review survey, oral health examination, physical development measurement and Childhood Autism Rating Scale (CARS) evaluation were conducted involving 147 children and adolescents aged 2-22 years with NDD from nine special education schools and rehabilitation institutions in Tianjin. Group comparisons were carried out using the Mann-Whitney  U  test,  Chi-square test, or Fisher s exact probability method. The correlation between dietary quality and dental caries was analyzed by adopting multiple linear regression analysis and restricted cubic spline.
		                        		
		                        			Results:
		                        			There were 46 children and adolescents (31.3%) in the non dental caries group and 101 children and adolescents (68.7%) in the dental caries group. The number of decayed missing and filled teeth (dmft) was 2.0 (4.0), and the MD score was 4.0 (2.0) points. There were 62 children and adolescents (42.2%) in the low MD scores group and 85 children and adolescents (57.8%) in the high MD scores group. There was no significant difference in MD scores between NDD children in the non dental caries group and those in the dental caries group [nondental caries group:4.0(2.0), dental caries group:4.0(2.0),  Z= -0.14, P >0.05]. The MD scores and dmft exhibited increasing and then decreasing trend ( P total =0.02,  P non lineary = 0.04 ). Children and adolescents with NDD in the MD high scores group had a lower number of dmft than those in the MD low scores group ( β= -2.00 , 95%CI =-3.39 to -0.62,  P <0.05). However, in children and adolescents with NDD and CARS scores ≥30, the above association was insignificant ( β=-0.63, 95%CI=-0.29-0.15, P >0.05).
		                        		
		                        			Conclusion
		                        			Children and adolescents with NDD who have dietary patterns similar to the Mediterranean diet, are found to have fewer dental caries, and this is observed among those with no or mild symptoms of autism spectrum disorder.
		                        		
		                        		
		                        		
		                        	
3.Clinicopathological and molecular characteristics of esophageal carcinoma with ductal differentiation: analysis of 17 cases
Wenjuan JIANG ; Shuang AO ; Yangyang CUI ; Lu LU ; Chunnian WANG
Chinese Journal of Pathology 2024;53(3):276-281
		                        		
		                        			
		                        			Objective:To investigate the clinicopathological features and molecular genetic characteristics of esophageal carcinoma with ductal differentiation, and to summarize the experiences in its diagnosis and treatment.Methods:A total of 17 cases of esophageal carcinoma with ductal differentiation diagnosed in Ningbo Clinical Pathological Diagnosis Center, Ningbo, China from June 2011 to December 2022 were collected. The clinical information and pathological diagnosis was reviewed. The tumor histological features and immunohistochemical results were analyzed. The next-generation sequencing was performed to detect and analyze the gene mutations in tumor samples.Results:The 17 patients included in this study were 54-77 years old, with a median age of 66 years. There were 16 males and 1 female. Among them, 9 cases were mainly carcinoma with ductal differentiation. The squamous epithelium on the tumor′s surface was accompanied by high-grade intraepithelial neoplasia. The tumor and atypical squamous epithelium were transitional, and the focus was accompanied by various proportions of squamous cell carcinoma component (less than 10%). The other 8 cases were mostly squamous cell carcinoma, basaloid squamous cell carcinoma or sarcomatoid carcinoma with various degrees of tumor specific differentiation and focal area of carcinoma with ductal differentiation (less than 10%). The tumor cells in the area with ductal differentiation were mainly arranged in small tubes, while the tubes showed a double-layer structure, including the inner cells and outer cells of the lumen. Immunohistochemical results showed that the outer cells of the tumorous tubules expressed p63, p40, CK5/6 and CK34βE12, while the inner cells expressed CK7. Compared with esophageal squamous cell carcinoma reported in the literature, the frequency of gene mutations such as MYC ( P=0.002), TP63 ( P=0.002), CDKN1C ( P=0.002) and NFE2L2 ( P=0.045) was significantly lower in this group of cases. At the signaling pathway level, the mutation frequency of NOTCH signaling pathway ( P=0.041) was significantly higher, while the mutation frequencies of NRF2 pathway ( P=0.013) and PI3K pathway ( P=0.009) were significantly lower than that of esophageal squamous cell carcinoma. Conclusion:Esophageal carcinoma with ductal differentiation is a type of esophageal carcinoma with unique morphology, and its molecular changes are also significantly different from those of conventional esophageal squamous cell carcinoma.
		                        		
		                        		
		                        		
		                        	
4.Systematic evaluation of eye tracking characteristics of emotional face in children and adolescents with autism spectrum disorder
LI Xinyu, XIONG Wenjuan, CUI Tingkai, QU Zhiyi, ZHANG Xin
Chinese Journal of School Health 2024;45(9):1227-1232
		                        		
		                        			Objective:
		                        			To apply eye-tracking technology to measure the fixation duration of children and adolescents with autism spectrum disorder (ASD) towards emotional faces, so as to provide potential objective indicators for the diagnosis and intervention of ASD.
		                        		
		                        			Methods:
		                        			Case-control studies related to emotional faces in ASD children and adolescents aged 3-18 years were searched in PubMed, Web of Science, CNKI and Wanfang, with a search period spanning from the inception of the databases to April 1, 2024. The Newcastle-Ottawa Scale (NOS) was employed to assess the quality of the retrieved articles, and a Meta analysis was conducted by Stata 17.0 software.
		                        		
		                        			Results:
		                        			A total of 18 articles were included, encompassing 361 participants in the ASD group and 413 in the control group. All studies scored ≥6 on the NOS, indicating high research quality. Compared to the control group, the ASD group demonstrated significantly shorter fixation duration ( P <0.01) towards specific emotional faces, including happy faces under the paradigm of self-made and same ethnicity emotional faces ( SMD =-1.05, -1.16), neutral faces in domestic literature ( SMD = -1.00), angry and sad faces under clinical diagnosis criteria ( SMD =-1.73, -1.29), and fearful faces under Chinese Classification and Diagnostic Criteria of Mental Disorders, Version 3 (CCMD-Ⅲ) ( SMD =-1.51).
		                        		
		                        			Conclusion
		                        			Children and adolescents with ASD exhibit abnormal eye tracking indicators towards certain emotional faces, which may serve as early warning indicators for the diagnosis of ASD.
		                        		
		                        		
		                        		
		                        	
5.Mini health technology assessment of weekly preparations of glucagon-like peptide-1 receptor agonist
Wenjuan HUANG ; Mengru CUI ; ABUDURUSULI•WUSHUER ; Shengjun ZHAO
China Pharmacy 2023;34(14):1768-1773
		                        		
		                        			
		                        			OBJECTIVE To comprehensively evaluate four weekly preparations of glucagon-like peptide-1 receptor agonist (GLP-1RA) marketed in China,and to provide evidence for hospitals to optimize drug catalogs and clinical rational drug use. METHODS Mini health technology assessment method was used to establish detailed evaluation rules according to A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions, and conduct comprehensive evaluation of four GLP- 1RA weekly preparations from aspects of pharmaceutical characteristics, effectiveness, safety, economy and other attributes. RESULTS Mini health technology assessment scores of the four GLP-1RA weekly preparations from high to low were dulaglutide 78.60 points, semaglutide 77.35 points,polyethylene glycol loxenatide 67.40 points, and exenatide microspheres 65.50 points, respectively. Dulaglutide had advantages in reducing blood sugar, arteriosclerotic cardiovascular disease, kidney benefits, and cost- effectiveness. Semaglutide had advantages in reducing blood sugar and weight loss, but its cost-effectiveness was lower than that of dulaglutide. Exenatide microspheres had advantages in the use of children, but its daily average treatment cost is the highest. Polyethylene glycol loxenatide needed further clinical evidence. CONCLUSIONS Four GLP-1RA weekly preparations all have high pharmaceutical comprehensive scores. Dulaglutide and semaglutide may have more comprehensive pharmaceutical value among them, while the use of exenatide microspheres for children is unique.
		                        		
		                        		
		                        		
		                        	
6.Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis
Shanghao LIU ; Hongmei ZU ; Yan HUANG ; Xiaoqing GUO ; Huiling XIANG ; Tong DANG ; Xiaoyan LI ; Zhaolan YAN ; Yajing LI ; Fei LIU ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Lei HUANG ; Fanping MENG ; Guo ZHANG ; Wenjuan WANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Qi ZHENG ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Zhangshu QU ; Min YUAN ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yongfeng YANG ; Wei YE ; Na LIU ; Rongyu TANG ; Quan ZHANG ; Qin LIU ; Gaoliang ZOU ; Ziyue LI ; Caiyan ZHAO ; Qian ZHAO ; Qingge ZHANG ; Huafang GAO ; Tao MENG ; Jie LI ; Weihua WU ; Jian WANG ; Chuanlong YANG ; Hui LYU ; Chuan LIU ; Fusheng WANG ; Junliang FU ; Xiaolong QI
Chinese Journal of Laboratory Medicine 2023;46(1):52-61
		                        		
		                        			
		                        			Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.
		                        		
		                        		
		                        		
		                        	
7.Clinical outcomes and early immune reconstitution in patients with acute lymphoblastic leukemia underwent allogeneic hematopoietic stem cell transplantation
Huiyu LI ; Tong CUI ; Shijia LI ; Shiyuan ZHOU ; Wenjuan ZHU ; Jing LI ; Xiao MA ; Xiaojin WU
Chinese Journal of Blood Transfusion 2023;36(9):777-781
		                        		
		                        			
		                        			【Objective】 To investigate the correlation between early immune reconstitution and clinical outcomes in patients with acute lymphoblastic leukemia (ALL) underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). 【Methods】 The basic information and treatment data of 99 patients with ALL undering allo-HSCT from December 2018 to February 2022 were collected. The proportions of CD3+ T, CD3+CD4+ T, CD3+CD8+ T and CD3-CD16+CD56+ NK cells were detected before and 30, 60 and 90 days after transplantation using flow cytometry. The correlation between early cellular immune reconstitution and neutrophil engraftment, platelet engraftment, infection, and acute and chronic graft-versus-host disease (GVHD) was analyzed. 【Results】 Among 99 ALL patients, the median time of neutrophil engraftment was day +11 (range, 8-28), and the median time of platelet engraftment was day +14 (range, 10-120). The cumulative incidence of blood stream infection (BSI) was 11.10% and the cumulative incidence of CMV within 100 days of transplantation was 40.40%. The cumulative incidence of EBV within 100 days was 7.10%. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 22.30%. The cumulative incidence of chronic graft-versus-host disease (cGVHD) within 1 year of transplantation was 16.20%. 1 -year cumulative relapse rate was 13.84%. The 1 -year cumulative disease-free survival (DFS) for all patients was 80.60% and the 1-year overall survival (OS) was 90.30%. The CD4+/CD8+ ratio was positively associated with the development of aGVHD at 30 days post-transplant (OR 1.21, 95CI 1.01-1.45, P<0.05). The proportion of CD16+ CD56+ NK cell were higher in the group without BSI than that in the BSI group before and 30 days after transplantation (P < 0.05). The proportion of CD4+ T-cell were lower in the CMV infection group than that in the group without CMV infection at 60 and 90 days post-transplant(P<0.05). The higher level of CD4+ T-cells at 60 days post-transplant was a protective factor for CMV infection within 100 days (HR 0.91, 95CI 0.84-0.99, P<0.05). 【Conclusion】 Early immune reconstitution after allo-HSCT in patients with ALL is associated with aGVHD, CMV and BSI.
		                        		
		                        		
		                        		
		                        	
8.Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture (version 2023)
Mi SONG ; Dan KONG ; Yuan GAO ; Yaping CHEN ; Xiaohua CHEN ; Yi CUI ; Junqin DING ; Leling FENG ; Lili FENG ; Jinli GUO ; Yun HAN ; Jing HU ; Sanlian HU ; Tianwen HUANG ; Yu JIA ; Yan JIN ; Xiangyan KONG ; Haiyan LI ; Hui LI ; Lunlan LI ; Shuixia LI ; Hua LIN ; Juan LIU ; Xuemei LU ; Ning NING ; Lingli PENG ; Lingyun SHI ; Changli WAN ; Jie WANG ; Qi WANG ; Yi WANG ; Ruifeng XU ; Ying YING ; Ping ZHANG ; Shijun ZHANG ; Wenjuan ZHOU
Chinese Journal of Trauma 2023;39(3):214-222
		                        		
		                        			
		                        			Hip fracture is considered as the most severe osteoporotic fracture characterized by high disability and mortality in the elderly. Improved surgical techniques and multidisciplinary team play an active role in alleviating prognosis, which places higher demands on perioperative nursing. Dysfunction, complications, and secondary impact of anaesthesia and surgery add more difficulties to clinical nursing. Besides, there still lack clinical practices in perioperative nursing for elderly patients with hip fracture in China. In this context, led by the Orthopedic Nursing Committee of Chinese Nursing Association, the Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture ( version 2023) is developed based on the evidence-based medicine. This consensus provides 11 recommendations on elderly patients with hip fracture from aspects of perioperative health education, condition monitoring and inspection, complication risk assessment and prevention, and rehabilitation, in order to provide guiding advices for clinical practice, improve the quality of nursing and ameliorate the prognosis of elderly patients with hip fracture.
		                        		
		                        		
		                        		
		                        	
9.Predictive value of CT texture analysis for recurrence in children with acute pancreatitis
Wei CUI ; Wenjuan ZHANG ; Lihua ZHOU ; Xin JIN ; Ding XIAO
Chinese Journal of Digestive Surgery 2021;20(4):459-465
		                        		
		                        			
		                        			Objective:To explore the predictive value of computed tomography (CT) texture analysis for the recurrence in children with acute pancreatitis (AP).Methods:The clinical diagnostic test was conducted. The clinical data of 56 children with primary AP who were admitted to Wuhan Fourth Hospital from January 2016 to January 2018 were collected. There were 13 males and 43 females, aged from 3.5 to 13.0 years, with a median age of 5.5 years. Based on follow-up in other hospitals, 20 children with recurrence of AP were allocated into recurrence group, and 36 children without recurrence were allocated into non-recurrence group. All the 56 children underwent abdomen plain and enhanced CT scan within 24 hours after first admission. Observation indicators: (1) comparison of clinicopathological features between two groups of children with AP. (2) comparison of CT texture parameters between two groups of children with AP. (3) diagnostic efficacy of clinical features and CT texture parameters. Follow-up using outpatient reexamination and telephone interview was conducted to detect recurrence of AP up to February 2020. The duration of follow-up required more than or equal to 24 months. The Shapiro Wilk test was used to analyze normality of measurement data. Measurement data with normal distribution were repre-sented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M (range) or M ( P25, P75), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was conducted using the Mann-Whitney U test. Clinical parameters and CT texture parameters with statistical differences were multivariate analyzed using the Logistic regression model. Receiver operating characteristic curve (ROC) analysis was used to evaluate the predictive efficacy of parameters for recurrence of AP. Results:(1) Comparison of clinicopatholo-gical features between two groups of children with AP: cases with or without complications were 14 and 6 for the recurrence group, versus 7 and 29 for the non-recurrence group, showing a significant difference between the two groups ( χ2=14.021, P<0.05). Cases with minimal, moderately severe or severe disease (severity of disease) were 2, 5, 13 for the recurrence group, versus 19, 11, 6 for the non-recurrence group, showing a significant difference between the two groups ( Z=5.414, P<0.05). (2) Comparison of CT texture parameters between two groups of children with AP: the energy value in the arterial phase on CT examination was 0.186(0.174,0.206)for the recurrence group and 0.413(0.405,0.425) for the non-recurrence group, showing a significant difference between the two groups ( Z=9.413, P<0.05). The energy value and entropy value in the venous phase on CT examination were 0.084(0.078,0.092) and 0.961(0.210,1.720) for the recurrence group, versus 0.135(0.124,0.156) and 0.372(0.210,0.535) for the non-recurrence group, showing significant differences between the two groups ( Z=4.763, 7.243, P<0.05). (3) Diagnostic efficacy of clinical parameters and CT texture parameters: results of multivariate analysis showed the complications, severity of disease, energy value in the arterial phase on CT examination were related factors for recurrence in children with AP, energy value and entropy value in the venous phase on CT examination were related factor for recurrence in children with AP ( odds ratio=0.874, 0.765, 0.837, 0.902, 0.813, 95% confidence interval as 0.802?0.985, 0.581?0.914, 0.753?0.897, 0.862?0.948, 0.765?0.873, P<0.05). Results of ROC analysis showed that that areas under curve (AUC) of complications, severity of disease in the clinical parameters were 0.734 and 0.832, the AUC of single CT texture parameter was 0.811?0.867, the AUC of clinico-pathological parameters combined with CT texture parameters was 0.882. Conclusion:CT texture analysis can early and non-invasively predict the recurrence of AP in children, and the combination of clinicopathological parameters with CT texture parameter has a better predictive efficacy.
		                        		
		                        		
		                        		
		                        	
10.Meta-analysis of effects of pulmonary rehabilitation on anxiety and depression in patients with chronic obstructive pulmonary disease
Yaru WANG ; Wenjuan LI ; Guandong WANG ; Shaoshuai CUI ; Yan LI ; Fang XI ; Haibo WANG
Chinese Journal of Modern Nursing 2021;27(15):1986-1991
		                        		
		                        			
		                        			Objective:To evaluate the effects of pulmonary rehabilitation on anxiety and depression in patients with chronic obstructive pulmonary disease (COPD) .Methods:The RCTs on application effects of pulmonary rehabilitation in COPD patients were searched in Cochrane Library, Medline, PsycINFO, PubMed, Web of Science, Embase, China Biology Medicine disc, CNKI, Wanfang Database and VIP Database from the establishment of those databases to August 1, 2020. Quality assessment and data extraction were performed for the included articles, and Meta-analysis was performed using Stata 14.0 and RevMan 5.3 software.Results:A total of 14 articles were included, including 1 106 patients. Meta-analysis results showed that pulmonary rehabilitation therapy was helpful to improve the symptoms of depression [ SMD= -0.79, 95% CI (-0.94--0.64) , P<0.01]and anxiety [ SMD=-0.61, 95% CI (-0.82--0.41) , P<0.01]in COPD patients. The results of subgroup analysis showed that the relief degree of depression and anxiety of patients in the intervention group was statistically significantly different from those of the control group ( P<0.01) when the intervention was longer than 3 months or less than or equal to 3 months. Conclusions:Pulmonary rehabilitation can improve the depression and anxiety of COPD patients, and the results of intervention for more than 3 months and less than or equal to 3 months are consistent. Combining the actual clinical situation, the shortest intervention time of 3 months can be used for intervention in order to obtain more ideal intervention effect.
		                        		
		                        		
		                        		
		                        	
            

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