1.Development and application of a three-dimensional digital visualization system for children's neck acupoints
Xiaojing AO ; Kun LI ; Yuhang LIU ; Xiaoxuan YANG ; Xing WANG ; Zhijun LI ; Xiaoyan REN ; Shaojie ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(9):1834-1840
		                        		
		                        			
		                        			BACKGROUND:Currently,there have been studies on three-dimensional digitalization and visualization systems for adult acupoints,but there are not many reports on the visualization of pediatric acupoints based on real pediatric digital sectional anatomical datasets. OBJECTIVE:To design and develop a digital three-dimensional visualization system for children's neck acupoints,to provide a basis for acupuncture and moxibustion,meridian and acupoint science teaching,clinical practice,acupuncture manipulation practice,and acupuncture safety research,and to provide a basis for the development of children's acupoint simulation system. METHODS:Based on a real cross-sectional anatomical dataset of pre-school boys,a three-dimensional digital virtual anatomical model of the neck region of children and internal multi-organ three-dimensional reconstruction were completed using PhotoShop 2021 and Digihuman Reconstruction System software.A database of 11 acupoints was compiled,including Fengfu and Fengchi,using the Unity database language.A three-dimensional model of children's neck anatomy,acupoint database,and writing acupuncture operation codes were integrated in Unity3D software.A three-dimensional digital visualization system for children's neck acupoints was successfully created,which integrated simulation acupoint positioning,three-dimensional acupoint anatomy,acupuncture training,clinical teaching,and acupuncture safety research. RESULTS AND CONCLUSION:(1)This study was based on real child specimens.Manual layer by layer segmentation of cross-sectional images was used to ensure the accuracy of the three-dimensional model to the greatest extent possible.The 3D software Digihuman Reconstruction System was utilized to extract and save independent segmentation data.PhotoShop 2021 software was collaborated with to complete dozens of three-dimensional reconstruction anatomical models of the outer skin of the neck and its internal bone structure,cervical spinal cord,blood vessels and nerves,muscles,and ligaments in children.The basic morphology and overall contour integrity verification of each independent structure were completed in MeshLab software.The 3-material research 13.0 software was applied for final fine tuning and anatomical position confirmation,successfully simulating and restoring the true anatomical morphology of the neck of preschool children.(2)Based on and referring to the national standards of the People's Republic of China,a database of commonly used acupoints in children's neck region was collected and organized,including their names,meridians,positioning,local anatomy,needle insertion levels,acupuncture methods,acupuncture accidents and prevention,acupoint indications,and two-dimensional anatomical sectional images.(3)Unity3D software was employed to integrate the three-dimensional model of children's neck,acupuncture simulation operation,and acupoint database,and a three-dimensional digital children's neck acupoint acupuncture visualization system was successfully constructed.The system displayed information on children's neck acupoints,two-dimensional and three-dimensional anatomical structures,and achieved two-dimensional and three-dimensional acupuncture simulation functions and acupuncture safety research functions for children's neck acupoints.Based on the ultra-thin sectional anatomical dataset of real child specimens,the first three-dimensional digital and visualization system for acupoints in the neck region of children had been constructed.Compared with previous acupoint acupuncture systems,it is more in line with the anatomical and morphological development characteristics of Asian children and has high application value in the fields of acupuncture safety research,clinical teaching,and acupuncture simulation training.
		                        		
		                        		
		                        		
		                        	
2.Digital characteristics of brainstem morphology and age-related development in young children
Yanan LIU ; Xing WANG ; Kun LI ; Ruifen SUN ; Xueying MA ; Lei ZHAO ; Yuhang LIU ; Yang YANG ; Yunteng HAO ; Ziyu LI ; Shaojie ZHANG ; Zhijun LI
Chinese Journal of Tissue Engineering Research 2024;28(11):1730-1736
		                        		
		                        			
		                        			BACKGROUND:Previous brain studies have mostly focused on adults and fetuses,and the developmental characteristics of young children's brainstems have rarely been studied. OBJECTIVE:To observe the brainstem development characteristics of healthy young children and to explore the age-related differences and their correlation with sex. METHODS:From January 2019 to April 2022,a retrospective study of 3.0T MRI images of 174 children aged 2 to 6 years in the Affiliated Hospital of Inner Mongolia Medical University was conducted,and the median sagittal diameter,area and angle of the brainstem(including midbrain,pons and medulla oblongata)were measured. RESULTS AND CONCLUSION:There is an age-related increase in the anterior and posterior diameters of the midbrain,pons and medulla oblongata in the 2-5 years old group as well as in the longitudinal diameter and area of the midbrain,pons and medulla oblongata in the 2-6 years old group.Except for the longitudinal diameter of the medulla oblongata,all others show a positive correlation with age(r>0,P<0.05).In the 2-3 years old group and 4-5 years old group,the children are in the rapid growth and development stage,and these two age groups can be used as the key observation indicators for the development of young children.The anterior-posterior diameter,longitudinal diameter,area of the pons and total brainstem area are strongly correlated with age,which can be used as the key observation indicators for the brainstem development in young children.
		                        		
		                        		
		                        		
		                        	
3.Biomechanical features of posterior"Y"osteotomy and fixation in treatment of ankylosing spondylitis based on finite element simulation analysis
Le ZHANG ; Zhenhua CAO ; Yunfeng ZHANG ; Yangyang XU ; Feng JIN ; Baoke SU ; Lidong WANG ; Xing WANG ; Ling TONG ; Qinghua LIU ; Yuan FANG ; Lirong SHA ; Haiyan WANG ; Xiaohe LI ; Zhijun LI
Chinese Journal of Tissue Engineering Research 2024;28(12):1842-1848
		                        		
		                        			
		                        			BACKGROUND:Ankylosing spondylitis is a progressive inflammation of spinal stiffness deformity caused by tissue ossification and fibrosis.The posture of ankylosing spondylitis patients is abnormal and their activities are limited that minor injuries can lead to thoracolumbar fractures.Traditional medical image observation limits doctors'preoperative decision planning and postoperative disease prevention for ankylosing spondylitis treatment. OBJECTIVE:Based on the spinal model of ankylosing spondylitis patients before and after posterior spinal cancellous ossification osteotomy("Y"osteotomy for short),to explore the biomechanical changes of"Y"osteotomy and fixation in the treatment of ankylosing spondylitis. METHODS:Based on the preoperative and postoperative CT images of an ankylosing spondylitis patient who went to the Second Affiliated Hospital of Inner Mongolia Medical University,a three-dimensional spine model(T11-S1)before and after"Y"osteotomy(L3 osteotomy)was reconstructed in Mimics 19.0 software.A 7.5 Nm torque was applied to the top of T11 vertebral body to simulate the movement of the spine under six conditions:flexion,extension,left bending,right bending,left rotation and right rotation.Finally,the range of motion of each vertebral body,the stress of each intervertebral disc,and the stress of the screw rod system were simulated. RESULTS AND CONCLUSION:(1)After"Y"type osteotomy and posterior fixation,the range of motion of all vertebrae in the spine decreased,and the loss rate of upper vertebrae was large(L1:77.95%).(2)The maximum stress of the spinal intervertebral disc before operation occurred at the L1-L2 segment(0.55 MPa),and the maximum stress of the spinal intervertebral disc after operation occurred at the T11-T12 segment(0.50 MPa),and the stress of intervertebral disc below T12 was far less than that before operation.(3)The maximum stress of the screw rod system(166.67 MPa)occurred in the upper and middle segments of the rod body and the root of the pedicle screw.(4)In conclusion,the"Y"type posterior fixation operation enhances the stability of the spine and reduces the range of motion of the spine.The vertebral body decompression of the fixed segment is great and the stress-shielding phenomenon of the lower vertebral body is significant.The stiffness of the rod body and the stress concentration area of the pedicle screw should be strengthened to avoid the fracture of the rod caused by stress fatigue.
		                        		
		                        		
		                        		
		                        	
4.Characteristics and significance of age-related changes in cervical uncinate process-related angle
Dezhou ZHANG ; Chaoqun WANG ; Jun SHI ; Kun LI ; Shaojie ZHANG ; Yuan MA ; Erfei HOU ; Danyang ZHAO ; Yunteng HAO ; Simin WANG ; Xiaohe LI ; Haiyan WANG ; Zhijun LI ; Xing WANG
Chinese Journal of Tissue Engineering Research 2024;28(36):5766-5772
		                        		
		                        			
		                        			BACKGROUND:As a unique structure of the cervical spine,the occurrence,development and progression of the uncovertebral joint directly affect the stability and range of motion of the cervical spine,and are also closely related to the pathogenesis of cervical spondylosis.A thorough understanding of the developmental characteristics of the uncovertebral joint is of great significance for the pathogenesis,diagnosis,and treatment of cervical spondylosis. OBJECTIVE:By using imaging and three-dimensional reconstruction technology to measure and observe the cervical uncinate process-related angle in a large sample of different age groups,the aim is to reveal the characteristics of its changes with age and vertebral growth,as well as its relationship with cervical spine stability. METHODS:Using a retrospective research design,we collected 1 447 cases of raw CT imaging data that meet the study requirements for complete cervical spine segments.The raw data were imported into Mimics 21.0 software in DICOM format for post-processing and measurement of angle of uncinate process and sagittal angle of uncinate process.The data were grouped based on gender,age,and side. RESULTS AND CONCLUSION:(1)With the increase of vertebral sequence,the angle of uncinate process increased in a V-shaped shape,and the lowest peak was at C5.The overall population showed a sharp peak with the increase of age,and the peak value mostly occurred in the age range of 30-39 years.(2)The sagittal angle of the uncinate process increased like a fishhook with the increase of the vertebral sequence,and the overall angle of the uncinate process increased with age,and the peak value mostly occurred in the age range of 20-29 years.The uncinate process angle and sagittal angle showed only partial significant differences between sides and genders(P<0.05).(3)It is concluded that the angle of the uncinate process increased with the increase of vertebral sequence in a V-shaped manner.The sagittal angle of the uncinate process increases like a fish hook with increasing vertebral order,while the two angles generally peak with increasing age.The angle of the uncinate process is about 131°,which may be closely related to the stability of the cervical spine,while the sagittal angle of the uncinate process is about 14°,and its function may play a certain role in limiting the excessive rotation of the cervical spine.
		                        		
		                        		
		                        		
		                        	
5.Micromorphological characteristics of the pedicle of the lower cervical vertebra
Kun LI ; Shaojie ZHANG ; Jun SHI ; Jian WANG ; Yanan LIU ; Lan DUO ; Yang YANG ; Yunteng HAO ; Zhijun LI ; Xing WANG
Chinese Journal of Tissue Engineering Research 2024;28(12):1890-1894
		                        		
		                        			
		                        			BACKGROUND:The lower cervical vertebral pedicle is the main stress site of the posterior column of the spine,which is of great significance for the maintenance of the stability of the human center of gravity and the reduction of shock.At present,there are few reports on the characteristics of the internal bone trabeculae,and the characteristics of the joint site of the vertebral pedicle with the articular process and the vertebral body.It is urgent to understand the fine anatomical structure of the vertebral pedicle and the relationship and function of each part. OBJECTIVE:To observe the microanatomical morphology of the vertebral pedicle by Micro-CT scanning of cervical vertebra specimens,and to measure and analyze the microstructure and morphometric parameters of the bone trabecula in the cervical pedicle under normal conditions to evaluate the safety performance of the cervical spine. METHODS:Micro-CT scanning was performed on 31 sets of cervical vertebrae C3-C7.By checking and reconstructing the areas of interest in the bone trabecular within the vertebral pedicle,the morphological characteristics and distribution direction of the bone trabecular within the cervical pedicle were observed,and the bone microstructure parameters were detected,and the differences in the bone microstructure of the C3-C7 vertebral pedicle were analyzed and compared. RESULTS AND CONCLUSION:(1)The Micro-CT images showed that the honeycomb bone trabeculae of the pedicle of the lower cervical spine presented a complex network of microstructures.The trabeculae near the cortical bone were lamellar and relatively compact,extending forward toward the vertebral body and backward toward the articular process lamina.Abatoid bone trabeculae extended into the medullary cavity and transformed into a network structure,and then into rod-shaped bone trabeculae.The rod-shaped bone trabeculae were sparsely distributed in the medullary cavity.(2)Statistical results of morphological parameters of bone trabeculae showed that bone volume fraction values in C4 and C5 were higher than that in C7(P<0.05).The bone surface/bone volume value in C7 was higher than that in C3,C4 and C6(P<0.05).The bone surface density of bone trabeculae in C7 was higher than that in C3,C4,C5 and C6(P<0.05).Trabecular thickness in C7 was higher than that in C3,C4 and C5(P<0.05).Bone surface/bone volume and bone surface density of the left pedicle bone trabecular were greater than those on the right side(P<0.05).(3)The microstructural changes of C3-C7 were summarized,in which the load capacity and stress of the C7 pedicle were poor,and the risk of injury was high in this area.
		                        		
		                        		
		                        		
		                        	
6.Development of a three-dimensional digital children's acupuncture point visualization system of Mongolian medicine
Yuhang LIU ; Ruifen SUN ; Jiya Rigen MU ; Xing WANG ; Zhijun LI ; Yanan LIU ; Yunteng HAO ; Yongqiang CAI ; Shaojie ZHANG ; Kun LI
Chinese Journal of Tissue Engineering Research 2024;28(20):3223-3228
		                        		
		                        			
		                        			BACKGROUND:Nowadays,there are increasing reports on the digitization and visualization system of acupuncture points for adults in traditional Chinese medicine,and the digitization and visualization system of acupuncture points for children in traditional Chinese medicine and the simulation system of acupuncture manipulation for Mongolian medicine training have been reported.However,there are no reports on relevant systems for children in Mongolian medicine. OBJECTIVE:To develop a simulation system of acupuncture points for children in Mongolian medicine,in the hope that it can be used for clinical teaching,manipulation practice and research on acupuncture safety. METHODS:Based on the tomographic anatomical dataset of preschool boys,a three-dimensional(3D)digital virtual anatomical model of children with multiple internal organs and tissues was constructed by using PhotoShop.2021 and Digihuman Reconstruction System software.The relevant annotation information database of 27 acupoints such as Dinghui acupoint of Mongolian medicine was compiled by the Unity database language.The Mongolian gold needle and silver needle were selected to record the acupuncture point teaching video on the 3D printed head and neck resin model of children.In Unity3D software,children's anatomical model,acupoint annotation information database and acupuncture operation video were integrated and coded,and a 3D digital children's Mongolian acupuncture acupoint visualization system integrating simulation acupuncture training,clinical teaching and acupuncture safety research was successfully created. RESULTS AND CONCLUSION:This study was based on real children's specimens.In order to reduce the error of two-dimensional segmentation,the manual layer-by-layer segmentation section image method was used to ensure the accuracy of the 3D model to the greatest extent.The Digihuman Reconstruction System was used to extract and save the individual segmentation data while maximizing the accuracy of the 3D model.PhotoShop.2021 software was used to complete the 3D reconstruction of the outer skin of the head and neck of children and the internal bony structure,cervical spinal cord,blood vessels and nerves,muscles and ligaments.After 3D reconstruction,the basic morphology of each independent structure and the integrity of the overall contour were verified in MeshLab software and the final fine adjustment and anatomical position confirmation were conducted using 3-matic research 13.0 software.The real anatomical morphology of the head and neck of preschool children was successfully simulated and restored.Unity3D software was used to integrate the 3D model of children,acupuncture operation video and acupoint annotation database,and the 3D digital Mongolian acupuncture acupoint visualization system for children was successfully constructed.Based on the real continuous fault ultra-thin dataset of preschool boys in China,China's first 3D digitization and visualization system of acupuncture points in the head and neck of children in Mongolian medicine was developed.Compared with the previous acupuncture soft works,this system is more suitable for the anatomical morphological development characteristics of Asian children,and has a high value of application in the fields of research on the safety of acupuncture in Mongolian medicine,clinical teaching and acupuncture simulation training.
		                        		
		                        		
		                        		
		                        	
7.Micro-CT analysis of distribution and structural characteristics of bone trabeculae in the calcaneus
Fengzhen ZHANG ; Ruifen SUN ; Ziyu LI ; Xing WANG ; Kun LI ; Zhijun LI ; Shaojie ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(24):3885-3889
		                        		
		                        			
		                        			BACKGROUND:The calcaneus is located in the lower posterior part of the foot and is heavily stressed.Calcaneus is complex and irregular in shape,surrounded by thin cortical bone and filled with a large number of trabeculae.The study of the microstructure,movement,and distribution of trabeculae is helpful to improve the understanding of calcaneus fracture. OBJECTIVE:The image data of calcaneus were obtained by scanning the calcaneus specimens with micro-computed tomography,and the structure of trabecular bone in calcaneus was analyzed to explore the morphology,distribution and structural characteristics of trabecular bone in calcaneus. METHODS:Dry adult calcaneus specimens were continuously scanned by micro-computed tomography,and the images were obtained after scanning and stored in DICOM format.Image data were imported into Hiscan Analyzer software to display clear and complete images of the sagittal plane,coronal plane,and the horizontal plane of the adult calcaneus.The trabecular movement of bone was observed layer by layer.According to the trabecular movement characteristics,the sagittal plane of the calcaneus was divided into six parts.A 49-mm2 region of interest was selected for each part at the same thickness as 7 mm.The three-dimensional microstructure of calcaneus and trabecular bone was obtained after three-dimensional reconstruction.After binarization,the volume fraction,surface density,trabecular thickness,trabecular space,and trabecular number parameters of the trabecular bone in the region of interest were calculated by software. RESULTS AND CONCLUSION:(1)The cortical layer of the calcaneus was very thin and filled with a large amount of cancellous bone,and the cortical layer of the horn of Gissane was obviously thickened.(2)The trabecular volume fraction in the upper part of the calcaneus was greater than that in the anterior part of the lower part of the calcaneus,the central triangle,the posterior part of the lower part of the calcaneus,and the base of the calcaneus,and the trabecular volume fraction in the tubercle of the calcaneus was greater than that in the anterior part of the lower part of the calcaneus,the central triangle,the posterior part of the lower part of the calcaneus,and the base of the calcaneus.The surface density of the trabecular bone in the tubercle of the calcaneus was higher than that in the front of the lower calcaneus,the middle triangle area,and the bottom of calcaneus,and the surface density of the trabecular bone in the upper part of calcaneal bone,and the lower part of the calcaneus was higher than that in the middle triangle area.The thickness of the trabecular bone in the upper part of the calcaneus was greater than that in the tubercle of the calcaneal bone.The bone trabecular space in the middle triangle was larger than that in the upper part of the calcaneus and calcaneal tubercles.The number of bone trabeculae in the calcaneal tubercles was greater than that in the middle triangle area.(3)These results indicate that the trabeculae of rod bone were mainly distributed in the middle triangle area.The surface density of trabeculae was the smallest,the volume fraction was smaller,and the space between trabeculae was the largest.This part of the bone is relatively loose.The compression resistance is poor when subjected to high impact.The trabecular bone fractures first occur,which is a prone site for fractures.
		                        		
		                        		
		                        		
		                        	
8.Effect of lncRNA MIF-AS1 on the malignant biological behavior of prostate cancer cells by regulating the miR-423-5p/PYCR1 axis
Jianbo YANG ; Jichun SHAO ; Zhijun ZENG ; Tao ZHAO ; Xing WANG
The Journal of Practical Medicine 2024;40(18):2544-2549
		                        		
		                        			
		                        			Objective To investigate the effect of long non-coding RNA(lncRNA)macrophage migration inhibitory factor antisense RNA1(MIF-AS1)on the malignant biological behavior of prostate cancer(PC)cells by regulating the miR-423-5p/pyrroline-5-carboxylic acid reductase 1(PYCR1)axis.Methods PC3 cells were cultured in vitro to knock down the expression of MIF-AS1 or down-regulate the expression of miR-423-5p.The expression of MIF-AS1,miR-423-5p and PYCR1 mRNA in tumor tissues and adjacent tissues and cells of PC patients were detected.The cell proliferation,apoptosis,migration,and invasion were detected and the expression of PYCR1 protein was detected by Western blot.The relationships between miR-423-5p,IF-AS1 and PYCR1 were verified.Results The MIF-AS1 and PYCR1 mRNA were observed to be highly expressed in the tumor tissues,while miR-423-5p was lowly expressed.Silenced MIF-AS1 inhibited the proliferation,migration and invasion of PC3 cells and up-regulated miR-423-5p induced cell apoptosis(P<0.05).Inhibition of miR-423-5p expression reversed the inhibitory effect of silencing MIF-AS1 on malignant behavior of PC3 cells(P<0.05).miR-423-5p was correlated with MIF-AS1 and PYCR1 by targeted regulation.Conclusion Silencing MIF-AS1 may inhibit the expression of PYCR1 by up-regulating miR-423-5p,thereby inhibiting the malignant behavior of PC cells.
		                        		
		                        		
		                        		
		                        	
9.Application of narrative nursing in long-term primary family caregivers of patients undergoing maintenance hemodialysis
Xuehua ZHANG ; Zhijun REN ; Shuping GAO ; Limin XING ; Longhua RAO ; Ying JIANG
Chinese Journal of Modern Nursing 2021;27(24):3297-3302
		                        		
		                        			
		                        			Objective:To explore the application effect of narrative nursing in long-term primary family caregivers of maintenance hemodialysis patients.Methods:Using the convenient sampling method, a total of 120 main family caregivers of maintenance hemodialysis patients who received hemodialysis treatment in Hemodialysis Room of a tertiary general hospital were selected as the research objects from May to August 2020. The patients were randomly divided into the observation group ( n=60) and the control group ( n=60) by random number table method. The observation group was given narrative nursing intervention, while the control group was given routine psychological nursing. Zarit Caregiver Burden Interview (ZBI) , Self-rating Anxiety Scale (SAS) and Beck Depression Scale (BDI-Ⅱ) were used to investigate the situation of caregivers in the two groups. Results:Before the intervention, there was no statistically significant difference in the total scores of ZBI, SAS and BDI-Ⅱ between the two groups ( P>0.05) . After the intervention, the total scores of ZBI, SAS and BDI-Ⅱ in the observation group were respectively 23.50 (15.00, 33.00) , 33.00 (27.00, 41.00) and 11.00 (8.00, 14.75) , which were lower than the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Narrative nursing can effectively reduce the long-term care burden of the main family caregivers of maintenance hemodialysis patients and reduce levels of anxiety and depression, which is worthy of clinical application.
		                        		
		                        		
		                        		
		                        	
10.Pressure boost in repair of soft tissue defect in limbs by free transplantation of thinned anterolateral thigh perforator flap
Yanxi TAN ; Zhijun PAN ; Lu HUANG ; Shuying GAO ; Chaoming LIU ; Xing YANG ; Feipeng MA ; Pei SU
Chinese Journal of Microsurgery 2020;43(4):342-346
		                        		
		                        			
		                        			Objective:To explore the surgical technique and clinical effect of pressure boost in repairing soft tissue defects of limbs with thinned anterolateral thigh perforator flap (ALTP) .Methods:From January, 2015 to December, 2018, 18 cases with soft tissue defects of limbs with various damages of blood vessels and nerves with explosure of tendon and bone. There were 13 males and 5 females aged between 18 to 56 (averaged of 36.3) years, which were 6 defects in shank, 4 in foot and ankle, 5 in forearm, and 3 in hand. The soft tissue defect area was 7 cm ×12 cm to 13 cm ×30 cm. Thinned ALTP was used to repair the wound surface. The perforating vessels of the distal flap were anastomosed with one branch of the internal vessel pedicle flap to increase the pressure hence the blood supply of the distal region. The donor sites were sutured directly or covered by skin graft. Followed-up was conducted by 1-2 monthly clinic visits and telephone or on-line review to check the flap survival and recovery of functions.Results:All flaps survived without arterial or venous crisis. One flap had partial necrosis at the distal end, and healed after dressing change. One case had a swelling flap due to a congestion beneath the flap. The wound achieved primary healing after removal of sutures, ligation of subcutaneous vessels and drainage of hematoma. All patients were followed-up for 6 to 18 (average, 9.5) months. All flaps had good appearance and texture. After rehabilitation treatment, most of the joint activity had been recovered: extension and flexion of wrists joints ranged 60°-80°, 70°-80° for metacarpophalangeal joints and 40°-60° for ankle joints. One patient underwent ankle joint dorsiflexion function reconstruction and flap thinning at 6 months after operation due to the defects of most of the extensor tendon.Conclusion:During the use of free ALTP to repair soft tissue defect of limbs, application of the technique of pressure boost is able to increase blood supply to the distal region of flap. It helps to reduce the incidence of infection and necrosis at the edge of the flap.
		                        		
		                        		
		                        		
		                        	
            
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