1.Association between sedentary behaviors with cardiorespiratory fitness and executive function among adolescents
SHANG Wenjin, YIN Xiaojian, WANG Jinxian, HONG Jun, SHI Lijuan, GUO Junfeng, WANG Tianyi, LIU Yixuan
Chinese Journal of School Health 2024;45(3):330-334
		                        		
		                        			Objective:
		                        			To explore the relationship between sedentary behavior with cardiorespiratory fitness and executive function in adolescents, and to provide some references for sedentary behavior prevention and executive function improvement.
		                        		
		                        			Methods:
		                        			From September  to December 2022, a total of 5 018 adolescents aged 13 to 18 years were selected by stratified random sampling method in Shanghai, Suzhou, Taiyuan,Wuyuan, Xingyi, and Urumqi to conduct physical activity survey, as well as cardiorespiratory fitness and executive function assessment. Pearson s correlation was used to analyze the relationship between sedentary behavior, cardiorespiratory fitness and executive function. The mediation effect model was fitted by the bootstrap mediation procedure in the PROCESS (version  3.3 ) SPSS macro compiled by Haves, and the mediation effect of adolescents  cardiorespiratory fitness in the relationship between static behavior and executive function was examined using model 4 in the PROCESS SPSS macro, where Boosrap method was used to compute the mediation effect of adolescents  cardiorespiratory fitness. where the Boosrap method was used to calculate confidence intervals for the mediating effects.
		                        		
		                        			Results:
		                        			Adolescents  daily sedentary time was positively correlated with both the refreshing function (1-back and 2-back) and the switch function reaction time ( r =0.05, 0.07, 0.05, P <0.01). Adolescent VO 2max  was negatively correlated with both the refreshing function (1-back,2-back) and the switching function ( r =-0.09,  -0.14 , -0.11,  P <0.01). Adolescents  daily sedentary time was negatively correlated with VO 2max  ( r =-0.04,  P <0.01); cardiorespiratory fitness mediated effect values between sedentary behavior and refreshing function (1-back and 2-back) and converted function were 0.20(95% CI =0.06-0.36), 0.43(95% CI =0.14-0.74) and 0.13 (95% CI =0.04-0.22), with mediating effect shares of 6.87%, 8.33% and 8.59%, respectively.
		                        		
		                        			Conclusion
		                        			The duration of sedentary behavior in adolescents is related to executive function performance, and cardiorespiratory fitness may serve as a mediator to mediate the association between sedentary behavior and executive function in adolescents.
		                        		
		                        		
		                        		
		                        	
2.Relation between self-perceived burden and quality of life in liver transplant recipients:the effecting path of anxiety and depression
Yun GUO ; Lina ZHOU ; Feng ZHANG ; Yumei CHEN ; Zonghui BU ; Wenjin WAN ; Yu WANG
Sichuan Mental Health 2024;37(5):444-450
		                        		
		                        			
		                        			Background Self-perceived burden,anxiety and depression are among the most important factors affecting quality of life.At present,there is a lack of understanding on the research status and influencing factors of self-perceived burden in liver transplant recipients.Previous studies have shown that self-perceived burden,anxiety,depression and quality of life are correlated in pairs,but the effecting path among the three are not yet clear.Objective To explore the correlation of self-perceived burden and anxiety/depression with quality of life in liver transplant recipients,so as to provide guidance for psychological nursing intervention in clinical patients.Methods A total of 200 patients liver transplant recipients were enrolled from the liver transplantation inpatient and outpatient clinics of Jiangsu Province Hospital and Qinhuai Medical Area,General Hosptial of Eastern Theater Command of People's Liberation Army of China from March 2022 to February 2023.Patients were evaluated using Self-perceived Burden Scale(SPBS),Hospital Anxiety and Depression Scale(HADS)and the Chinese version of Post Liver Transplant Quality of Life Questionnaire(pLTQ).Spearman correlation analysis was used to examine the correlation among the scales.A structural equation model using Mplus 8.3 was utilized to testify the relationship among self-perceived burden,anxiety/depression and quality of life in liver transplant recipients.Bootstrap method was used to test the effecting pathway.Results There were statistically significant differences in SPBS scores of liver transplant recipients with different levels of education and fannual family income(H=9.656,18.796,P<0.05).There were statistically significant differences in HADS scores of liver transplant recipients with different numbers of somatic symptoms(H=9.859,P<0.05).There were statistically significant differences in the Chinese version of pLTQ scores of liver transplant recipients with different levels of education,postoperative survival time and numbers of somatic symptoms(H=6.892,8.023,16.099,P<0.05).The total and each dimension scores in SPBS of liver transplant recipients were positively correlated with the total score and anxiety/depression dimension scores in HADS(r=0.464~0.586,0.460~0.593,0.286~0.408,0.464~0.583,P<0.01)and negatively correlated with the total score and each dimension scores in the Chinese version of pLTQ(r=-0.572~-0.416,-0.599~-0.441,-0.365~-0.213,-0.559~-0.428,P<0.01).Structural equation model denoted that self-perceived burden negatively affected quality of life(β=-0.186,P<0.01).Anxiety/depression also negatively affected quality of life(β=-0.679,P<0.01).The self-perceived burden indirectly affected the quality of life of liver transplant recipients through anxiety and depression,with an effect value of-0.429,accounting for 69.76%of the total effect.Conclusion The quality of life in liver transplant recipients may be related to their self-perceived burden and anxiety/depression.Self-perceived burden may affect the quality of life of liver transplant patients through anxiety and depression.
		                        		
		                        		
		                        		
		                        	
3.Percutaneous radiofrequency ablation of renal tumor under local anesthesia guided by ultrasound and CT
Wenjin YANG ; Xiaofeng WANG ; Haifeng HUANG ; Fan ZHANG ; Shengjie ZHANG ; Guangxiang LIU ; Changwei JI ; Hongqian GUO
Chinese Journal of Urology 2024;45(5):360-365
		                        		
		                        			
		                        			Objective:To explore the effectiveness and safety of percutaneous radiofrequency ablation for renal tumors, guided by both ultrasound and CT, under local anesthesia.Methods:A retrospective analysis was conducted on the clinical data of 40 patients with renal tumors admitted to Nanjing Drum Tower Hospital between January 2018 and December 2022. This treatment involved ultrasound/CT dual-guided radiofrequency ablation under local anesthesia. The cohort included 33 males and 7 females, with an average age of (61.5±11.9) years old and a body mass index (BMI) of (24.79±3.37) kg/m 2. The tumors were located in the left kidney in 20 cases and the right kidney in 16 cases, with 4 cases involving bilateral renal tumors. There were 44 tumors in 40 patients, with the maximum tumor diameter ranging from 1.0 to 4.0 cm [mean (2.3 ± 0.7) cm]. Distribution by kidney pole was as follows: 15 cases at the upper pole, 21 at the middle pole, and 8 at the lower pole. Of the tumors, 23 were exophytic, 5 were endophytic, and 16 exhibited mixed features. There were 2 patients with multiple metastases before surgery(including 1 patient with bilateral renal tumor). Preoperative serum creatinine level was 68.0(56.5, 87.5)μmol/L, and the estimated glomerular filtration rate (eGFR) was 114.2 (79.6, 132.4) ml/(min·1.73 m 2). All patients underwent renal biopsy before or during radiofrequency ablation. Percutaneous radiofrequency ablation surgery was performed using ultrasound and CT dual guidance on all patients, ensuring complete tumor destruction during the procedure as confirmed by dual positioning. Patients with bilateral tumors underwent two separate surgeries, spaced one month apart. Postoperatively, closely monitor the patient's vital signs and conduct long-term follow-ups to record any recurrence and metastasis. Results:In this series, all 40 procedures (involving 44 renal units) were successfully completed under local anesthesia without any need for blood transfusion, conversion to open surgery, or perioperative deaths. The average radiofrequency ablation time was (9.5 ± 3.6) min. Tumor characteristics included predominantly exophytic growths (23 cases, 52.3%), with 31 cases (70.5%) located more than 7 mm from the collecting system and 28 cases (63.6%) positioned posteriorly. Thirteen cases (29.5%) were entirely outside the polar line. The average R. E.N.A.L. nephrometry score was 6.1±0.2. Pathological examination revealed 34 cases of clear cell carcinoma, 2 of papillary renal cell carcinoma, 4 of unclassified renal cell carcinoma, and 4 benign renal tumors. In this cohort, two patients with bilateral renal tumors exhibited benign tumors on one side, while two other patients had malignant tumors in both kidneys. All 40 malignant tumors identified in 38 cases were classified at stage cT 1a.Postoperative serum creatinine level was 71.5 (59.0, 94.3) μmol/L, showing no statistically significant change from preoperative levels ( P > 0.05). Similarly, the eGFR post-operation was 107.4 (79.7, 132.2) ml/(min·1.73 m 2), which also did not differ significantly from preoperative values ( P > 0.05). There were no postoperative complications of Clavien-Dindo grade ≥Ⅱ, except for one case of severe pain (score 7-10). The follow-up period ranged from 15 to 70 months. Among the 38 cases, 36 patients did not have distant metastasis before surgery. There were 2 patients (5.5%) with local recurrence within 60 months after surgery. Among them, one case relapsed 6 months after radiofrequency ablation and was treated with partial nephrectomy. The patient was followed up for 60 months after the second treatment, and no local recurrence occurred. Another patient relapsed 41 months after surgery and was treated with radiofrequency ablation again. The patient was followed up for 12 months after the second treatment, and no local recurrence occurred. Two patients with distant metastasis before surgery were treated with targeted therapy plus immunotherapy for 12 months after surgery. One case had local recurrence 8 months after surgery and was treated with partial nephrectomy. The patient was followed up for 60 months after partial nephrectomy and no local recurrence occurred. Another patient with bilateral renal tumors developed left kidney recurrence 34 months after radiofrequency ablation, and underwent left partial nephrectomy. The right kidney recurred 42 months after radiofrequency ablation and underwent radiofrequency ablation again. After the second right renal radiofrequency ablation, no local recurrence occurred during 12 months of follow-up. Conclusions:Ultrasound/CT dual-guided percutaneous radiofrequency ablation, performed under local anesthesia for treating renal tumors, has minimal impact on the patient's renal function. The procedure boasts a low complication rate, with no postoperative severe complications. Additionally, the postoperative tumor control is effective, making it a safe and minimally invasive surgical option.
		                        		
		                        		
		                        		
		                        	
4.Analysis of Oligosaccharide Mapping of Atractylodis Rhizoma from Different Habitats
Likun CHANG ; Wenjin ZHANG ; Ye CAO ; Jian YANG ; Sheng WANG ; Chuanzhi KANG ; Li ZHOU ; Yuefeng WANG ; Chaogeng LYU ; Lanping GUO
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(23):189-196
		                        		
		                        			
		                        			ObjectiveTo establish a method for the analysis of oligosaccharides in Atractylodes lancea rhizome based on ultra-performance liquid chromatography tandem quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and a method for the quantification of oligosaccharides in A. lancea rhizome based on UPLC-evaporative light scattering detector (ELSD), and to investigate the oligosaccharide characteristics of A. lancea rhizome from different habitats. MethodUPLC-Q-TOF-MS was used to identify the oligosaccharides in A. lancea rhizome with the mobile phase of 0.1% ammonia acetonitrile solution (A)-0.1% ammonia solution (B) for gradient elution (0-0.5 min, 98%A; 0.5-2.0 min, 98%-89%A; 2.0-2.5 min, 89%-86%A; 2.5-5.5 min, 86%-80%A; 5.5-6.5 min, 80%-72%A; 6.5-9.5 min, 72%-63%A; 9.5-14.0 min, 63%-50%A; 14.0-16.0 min, 50%A; 16.0-16.5 min, 50%-98%A; 16.5-20 min, 98%A), the column temperature of 60 ℃ and the flow rate of 0.2 mL·min-1. Electrospray ionization (ESI) was used to collect data in negative ion mode and the detection range was m/z 50-1 500. The qualitative analysis of oligosaccharides was accomplished by retention time, relative molecular weight, primary and secondary MS information of characteristic fragment ions in combination with reference substance information. UPLC-ELSD was employed to determine the contents of nine oligosaccharides in A. lancea rhizome with the mobile phase of 0.1% ammonia acetonitrile solution (A)-0.1% ammonia solution (B) for gradient elution (0-1 min, 98%-75%A; 1-7 min, 75%-70%A; 7-18 min, 70%-55%A; 18-23 min, 55%A; 23-23.5 min, 55%-98%A; 23.5-28 min, 98%A), the drift tube temperature of ELSD was set at 50 ℃. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to analyze the classification and differential components between A. lancea rhizome from different habitats. ResultA total of 24 oligosaccharides, containing 11 pairs of isomers, were identified from A. lancea rhizome. Among them, compared with samples from Anhui, Chongqing, Nanjing and Shaanxi, the contents of kestose(GF2), 1F-fructofuranosylnystose (GF4), kestohexose (GF5), fructo-oligosaccharide DP10 (GF9) in samples from Maoshan were statistically significant (P<0.05), and the total mass fraction of sucrose (GF1)-GF9 reached 16.47%. The peak area ratio of fructose-fructose oligosaccharide to its isomer sucrose-fructose oligosaccharide was greater than 1 in samples from Maoshan. ConclusionThe types and contents of oligosaccharides in A. lancea rhizome vary greatly among different habitats, and the peak area ratio of fructose-fructose oligosaccharide to sucrose-fructose oligosaccharide >1 may be one of the geoherb characteristics of A. lancea rhizome, which can provide a reference for the development, utilization and quality control of this herb. 
		                        		
		                        		
		                        		
		                        	
5.Research progress in trauma registration system
Zhenxia GUO ; Shiyao WANG ; Yatao LIU ; Xingwen HAN ; Wenji WANG ; Pei CHU ; Yongwei LIU ; Xiang LI ; Michael NERLICH ; Wenjin WANG ; Liping LIU
Chinese Journal of Trauma 2022;38(4):374-379
		                        		
		                        			
		                        			Trauma registration is an important tool to record the process and timeline in the treatment of trauma patients. The operation of trauma database is of great significance for reducing the mortality of patients, promoting the construction of trauma treatment system, and providing reference for policy-making. Trauma registration system has been established in the United States, United Kingdom, Germany and other developed countries for many years. However, the domestic system is still at an initial stage, and there are problems like data deficiencies, data incoherence, no item of complications, no treatment data after discharge and limits of human and financial resources. Therefore, there is room for improvements in terms of personnel fixation, financial support and continuous data monitoring should be further improved. In this study, the authors summarize the traum registration system from aspects of basic situation both at home and abroad, data analysis, clinical value, operation mechanism and challenges so as to provide important data for clinical researches.
		                        		
		                        		
		                        		
		                        	
6.Effect of Palrnatine on lipopolysaccharide-induced acute lung injury by inhibiting activation of the Akt/NF-κB pathway
KAN XINGCHI ; CHEN YINGSHENG ; HUANG BINGXU ; FU SHOUPENG ; GUO WENJIN ; RAN XIN ; CAO YU ; XU DIANWEN ; CHENG JI ; YANG ZHANQING ; XU YANLING
Journal of Zhejiang University. Science. B 2021;22(11):929-940
		                        		
		                        			
		                        			Inflammation plays an important role in the development of acute lung injury (ALI). Severe pulmonary inflammation can cause acute respiratory distress syndrome (ARDS) or even death. Expression of proinflammatory interleukin-1β(IL-1β) and inducible nitric oxide synthase (iNOS) in the process of pulmonary inflammation will further exacerbate the severity of ALI. The purpose of this study was to explore the effect of Palrnatine (Pa) on lipopolysaccharide (LPS)-induced mouse ALI and its underlying mechanism. Pa, a natural product, has a wide range of pharmacological activities with the potential to protect against lung injury. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed to detect the expression and translation of inflammatory genes and proteins in vitro and in vivo. Immunoprecipitation was used to detect the degree of P65 translocation into the nucleus. We also used molecular modeling to further clarify the mechanism of action. The results showed that Pa pretreatment could significantly inhibit the expression and secretion of the inflammatory cytokine IL-1β, and significantly reduce the protein level of the proinflammatory protease iNOS, in both in vivo and in vitro models induced by LPS. Further mechanism studies showed that Pa could significantly inhibit the activation of the protein kinase B (Akt)/nuclear factor-κB (NF-κB) signaling pathway in the LPS-induced ALI mode and in LPS-induced RAW264.7 cells. Through molecular dynamics simulation, we observed that Pa was bound to the catalytic pocket of Akt and effectively inhibited the biological activity of Akt. These results indicated that Pa significantly relieves LPS-induced ALI by activating the Akt/NF-κB signaling pathway.
		                        		
		                        		
		                        		
		                        	
7.Experimental study on the chronic alcohol-induced testicular microvascular injury and spermatogenic cell morphological changes by contrast-enhanced ultrasound
Huanzhong SU ; Ensheng XUE ; Longcheng HONG ; Zhiyong LI ; Wenjin LIN ; Jie GUO
Chinese Journal of Ultrasonography 2020;29(11):992-998
		                        		
		                        			
		                        			Objective:To explore the value of contrast-enhanced ultrasound and its quantitative analysis technology in the evaluation of testicular microvascular injury caused by chronic alcoholism, as well as its relationship with the morphological changes of testicular spermatogenic cells.Methods:Seventy-two New Zealand white rabbits were randomly divided into control group (S group), low-dose alcohol group (L group), medium-dose alcohol group (M group), and high-dose alcohol group (H group). Then, the rabbits were subdivided into the groups of S1, S2, S3, L1, L2, L3, M1, M2, M3, H1, H2, H3 according to different time points (30 d, 60 d, 90 d). The rabbits in each group were examined by routine ultrasound before the experiment, followed by contrast-enhanced ultrasound examination. Testicular tissues were taken for pathological examination under light and electron microscope.Results:①The peak intensity and area under the curve of ultrasound contrast parameters gradually decreased with the increase of dosage and duration of alcohol feeding (all P<0.05), and the curvature also gradually decreased (all P<0.05). The differences of peak time, mean transit time, and peak half-time were not statistically significant (all P>0.05). ②With the increase of alcohol dosage and duration under the light microscope, the seminiferous tubule epithelium gradually became thinner, and the sperm in the cavity gradually decreased or no sperm was produced. The Johnsen′s score of testicular tissue decreased with the increase of alcohol dosage and duration (all P<0.05). The cytoplasmic mitochondria of the microvascular endothelial cells were vacuolated under the electron microscope. With the dosage and duration of alcohol feeding, the endothelial cells were vacuolated and even shed, and the basement membrane was interrupted. Conclusions:Alcohol could damage the testicular microvessels and spermatogenic cells in a dose-effect and time-effect relationship. Contrast-enhanced ultrasound can be used to evaluate the microvessel damage of testis caused by chronic alcoholism and indirectly reflect the morphological changes of spermatogenic cells.
		                        		
		                        		
		                        		
		                        	
8.Dynamic changes of serum Tau proteins and their correlation with cognitive dysfunction in patients with acute traumatic brain injury
Wenjin YANG ; Yijun GUO ; Ping ZHENG ; Wusong TONG ; Ruizhong WANG ; Ronghong JIAO ; Gaoyi LI ; Dabin REN ; Chunfang ZHAO ; Ping NI ; Xiaohong PAN
Chinese Journal of Trauma 2018;34(1):35-39
		                        		
		                        			
		                        			Objective To investigate dynamic changes of serum Tau proteins and their correlation with cognitive dysfunction in patients with acute traumatic brain injury (TBI).Methods A total of 95 patients with acute TBI were retrospectively studied by case-control study.There were 61 males and 34 females,with age of 16-65 years [(40.7 ± 13.6)years].The Glasgow coma scale (GCS) was 3-8 points in 9 patients,9-12 points in 11,and 13-15 points in 75.A total of 30 healthy physical examinees were recruited as control group.The levels of Tau proteins were measured at days 1,3,5,7 and 14 after TBI.The cognitive dysfunction was evaluated by the Montreal Cognitive Assessment (MoCA) score at 6 months after injury.The correlation between Tau protein levels at different time points and MoCA was determined.Results The serum Tau proteins of TBI group was significantly higher than that of control group at all time points (P < 0.05).In TBI group,39 (41%) out of 95 patients developed cognitive dysfunction assessed by MoCA scale.The main manifestations of cognitive dysfunction were the defects in visual spatial and acting function,delayed memory,language,abstract,attention and calculation,with statistical significance compared with control group (allP < 0.05).The serum Tau proteins of patients with cognitive dysfunction were significantly higher than those without cognitive dysfunction at all time points after TBI (P < 0.05).Tau proteins at days 1,3,5 after TBI was significantly correlated with cognitive dysfunction at 6 months after TBI (P < 0.05).Conclusions The levels of serum Tau proteins show a significant increase after TBI,the early changes of which are statistically related to cognitive dysfunction.The early changes of serum Tau protein after TBI can be used as a reliable biomarker for early prediction of cognitive function prognosis.
		                        		
		                        		
		                        		
		                        	
9.Dynamic changes and their clinical significance of serum insulin-like growth factor-1 in patients with acute traumatic brain injury
Yijun GUO ; Ping ZHENG ; Wusong TONG ; Wenjin YANG ; Ruizhong WANG ; Ronghong JIAO ; Zhucai KUANG ; Bin HE ; Chunfang ZHAO ; Ping NI
Chinese Journal of Trauma 2017;33(8):709-713
		                        		
		                        			
		                        			Objective To investigate the dynamic changes of serum insulin-like growth factor-1 (IGF-1) in acute traumatic brain injury (TBI) as well as their correlations with the initial severity of TBI and prognosis.Methods A total of 229 patients with acute TBI admitted from September 2014 to June 2016 were retrospectively studied.Patients were further classified as mild TBI group (GCS 13-15 points),moderate TBI group (GCS 9-12 points) and severe TBI group (GCS 3-8 points) according to Glasgow coma score (GCS).The control group consisted of 30 healthy subjects.The prognosis was evaluated by using Glasgow outcome scale (GOS) at 6 months after TBI.The IGF-1 levels were further tested at days 1,3,5,7 and 14 and their correlations with the initial GCS and GOS at 6 months after injury were evaluated.Results (1) The serum IGF-1 levels of mild,moderate and severe TBI group at all time points were significantly lower than those of the control group (P < 0.05);the serum IGF-1 levels of severe and moderate TBI groups at all time points after injury were significantly lower than those of the mild TBI group (P <0.05);the serum IGF-1 levels of the severe group at days 1,3,5 and 7 d after injury were lower than those of the moderate TBI group (P<0.05).(2) IGF-1 levels were significantly different between the two groups (P < 0.05) at different time points during the follow-up of 6 months.(3)IGF-1 levels were positively correlated with both GCS and GOS at the acute stage of TBI and sub-acute stage following TBI (P < 0.05).Conclusion The dynamic changes of serum IGF-1 levels in patients with acute TBI are related to both initial severity of TBI and the neurological outcomes and can be used as a reliable biomarker for early severity assessment and prognostic prediction of TBI.
		                        		
		                        		
		                        		
		                        	
10.Analysis of deafness-related gene mutations in 88 non-syndromic hearing loss patients in Fuzhou city
Wenjin LIN ; Shunmin GUO ; Xiaomei XU ; Rongqing XU ; Yamin ZHANG
Chinese Archives of Otolaryngology-Head and Neck Surgery 2016;23(6):335-337
		                        		
		                        			
		                        			OBJECTIVE To investigate the deafness-related gene mutation frequency and hotspots in patients of Fuzhou city with non-syndromic hearing loss (NSHL). METHODS Peripheral blood samples were obtained from 88 cases of patients with hearing loss after clinical history inquiry and clinical examination. Their genomic DNA was extracted from peripheral blood by extraction kits to undergo polymerase chain reaction, traditional capillary electrophoresis sequencing and High-throughput sequencing so as to detect the mutations of deafness-related gene. RESULTS Among the 88 patients with NSHL, the gene mutation frequency was 34.09%.In the patients, 14 cases had mitochondrial 12 S rRNA mutations, six cases had GJB2 gene mutations and three cases had SLC26A4 mutations, two cases had MYO15A mutations, the other five cases had MYO7A, OTOF, TECTA, TMC1 and ILDR1 gene mutation respectively. CONCLUSION Among the 88 patients with NSHL, the most frequent mutation causing hereditary deadness was mutation in mitochondrial 12 S rRNA, followed by GJB2 and SLC26A4, The other genes such as MYO7A, OTOF, TECTA, TMC1 and ILDR1 gene were infrequent. The study could provide theoretical reference in genetic diagnosis, prevention and cure of hearing loss.
		                        		
		                        		
		                        		
		                        	
            

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