1.Structure, content and psychometric properties of assessment tools for interoceptive function: a scoping review based on COSMIN and ICF
Xiaoxiao WANG ; Lu QU ; Jiaxin WANG ; Meiping ZHAO ; Muzi LI ; Qiaoyun LIU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(2):172-183
		                        		
		                        			
		                        			ObjectiveTo review the interoceptive assessment tools in terms of structure, content and psychometric properties, based on the framework of the International Classification of Functioning, Disability and Health (ICF). MethodsThe literature on interoceptive evaluation tools was retrieved from databases of CNKI, PubMed, Medline and EBSCO. The principal structures and contents of the assessment tools were analyzed based on the ICF framework, and the quality of the psychometric properties were appraised using COSMIN. ResultsA total of 13 interoceptive assessment tools were ultimately included, involving 16 literature references. There were five interoceptive sensitivity tools, four accuracy tools and four awareness tools. In terms of content, interoceptive sensitivity tools involved 33 categories of body functions, six categories of activities and participation, and one of environmental factors; while interoceptive accuracy tools only involved seven categories of body function, and two of activities and participation items; interoceptive awareness tools involved 30 categories of body function, four categories of activities and participation, and three of environmental factors. In terms of psychometric properties, Body Perception Questionnaire-Short Form (BPQ-SF) was the sensitivity tool with the best reliability and validity (qualified rate of 7/8), followed by Interoceptive Sensitivity Questionnaire (ISQ) (qualified rate of 6/8). Most of the accuracy tools adopted standardized measurement methods, but lacked sufficient reliability and validity verification. The awareness tools were good in reliability and validity (qualified rate above 5/8), especially Multidimensional Assessment of Interoceptive Awareness (MAIA-1) and Body Awareness Questionnaire (BAQ) (qualified rate of 8/8). ConclusionBPQ-SF and ISQ are recommended for interoceptive sensitivity assessment, Water-loading Test and Heart-beat Tracking Task for interoceptive accuracy assessment, and MAIA-1 and BAQ for interoceptive awareness assessment. 
		                        		
		                        		
		                        		
		                        	
2.Quality Evaluation of Atractylodis Macrocephalae Rhizoma in Different Production Methods Based on Traditional Traits
Jinxiu QIAN ; Yihan WANG ; Yapeng WANG ; Guoliang YU ; Qiuxiang PAN ; Jiawei SHI ; Meiping CHEN ; Yangqing LIU ; Lun LU ; Yanmeng LIU ; Tiegui NAN ; Liping KANG ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):43-52
		                        		
		                        			
		                        			ObjectiveBased on the experience of traditional quality evaluation, the quality of Atractylodis Macrocephalae Rhizoma(AMR) with different production methods such as direct seeding, transplanting after seedling raising, topping and non-topping, and difference in growth years was compared. MethodVernier caliper was used to measure the trait data of AMR in different production methods. Paraffin sections of AMR with different production methods were made by saffron solid green staining, and the microstructure was observed. The contents of water-soluble and alcohol-soluble extracts in AMR with different production methods were determined according to the 2020 edition of Chinese Pharmacopoeia. The content of water-soluble total polysaccharides in AMR with different production methods was detected by sulfuric acid-anthrone method. Fiber analyzer was used to detect the content of fiber components in AMR with different production methods. The contents of monosaccharides, oligosaccharides and some secondary metabolites in AMR with different production methods were detected by ultra performance liquid chromatography(UPLC), and the differences of chemical components were compared by multivariate statistical analysis methods such as principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA). ResultIn terms of traits, the 3-year-old AMR with direct seeding and without topping was close to the high-quality AMR with "phoenix-head and crane-neck, strong sweetness and clear aroma" recorded in ancient materia medica, followed by the 3-year-old AMR with topping after transplanting, while the 2-year-old AMR with topping after transplanting with high market circulation rate was generally fat and strong with mild odor. In the microscopic aspect, the arrangement of xylem vessels and fiber bundles in the 3-year-old samples formed two obvious rings. Compared with the 2-year-old samples cultivated in Bozhou and Zhejiang, the 3-year-old samples without topping after transplanting had more wood fibers. In terms of chemical composition, the contents of 70% ethanol extract, fructose, glucose, sucrose, 1-kestose, atractylenolide Ⅰ, chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid and other components in 3-year-old AMR with direct seeding and without topping were significantly higher than those in the other three samples(P<0.05). The contents of cellulose, 70% ethanol extract, sucrose, atractylenolide Ⅰ, atractylone and other components in 3-year-old AMR with topping after transplanting were significantly higher than those in the 2-year-old AMR with high market circulation rate(P<0.05), while the contents of water-soluble extract and water-soluble total polysaccharides in 2-year-old samples with topping after transplanting were significantly higher than those in the 3-year-old AMR with topping after transplanting, direct seeding and without topping(P<0.05). ConclusionUnder the current mainstream production mode, too much manual intervention makes AMR heavily enriched in polysaccharides and increased the yield, but the accumulation of sweet substances, fragrant substances and fiber substances is insufficient, which affects its quality. The current quality standard of AMR has some shortcomings in guiding the high quality production of it, it is suggested to revise the quality standard of AMR, supplement the quantitative analysis of secondary metabolites, and strengthen the production of imitation wild AMR. 
		                        		
		                        		
		                        		
		                        	
3.A multicenter clinical study of critically ill patients with sepsis complicated with acute kidney injury in Beijing: incidence, clinical characteristics and outcomes
Na GAO ; Meiping WANG ; Li JIANG ; Bo ZHU ; Xiuming XI
Chinese Critical Care Medicine 2024;36(6):567-573
		                        		
		                        			
		                        			Objective:To investigate the epidemiological characteristics and prognosis of critically ill patients with sepsis combined with acute kidney injury (AKI) in intensive care unit (ICU) in Beijing, and to analyze the risk factors associated with in-hospital mortality among these critically ill patients.Methods:Data were collected from the Beijing AKI Trial (BAKIT) database, including 9 049 patients consecutively admitted to 30 ICUs in 28 tertiary hospitals in Beijing from March 1 to August 31, 2012. Patients were divided into non-AKI and non-sepsis group, AKI and non-sepsis group, non-AKI and sepsis group, AKI and sepsis group. Clinical data recorded included demographic characteristics, primary reasons for ICU admission, comorbidities, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) within 24 hours of ICU admission, physiological and laboratory indexes, treatment in the ICU, AKI staging based on the Kidney Disease: Improving Global Outcomes (KDIGO), as well as the prognostic indicators including length of stay in ICU, length of stay in hospital, ICU and in-hospital mortality. The primary endpoint was discharge or in-hospital death. Multivariate Logistic regression analysis was used to investigate the risk factors for hospital death in ICU patients. Kaplan-Meier survival curve was drawn to analyze the cumulative survival of ICU patients during hospitalization.Results:A total of 3 107 critically ill patients were ultimately enrolled, including 1 259 cases in the non-AKI and non-sepsis group, 931 cases in the AKI and non-sepsis group, 264 cases in the non-AKI and sepsis groups, and 653 cases in the AKI and sepsis group. Compared with the other three group, patients in the AKI and sepsis group were the oldest, had the lowest mean arterial pressure (MAP), and the highest APACHEⅡscore, SOFA score, blood urea nitrogen (BUN), and serum creatinine (SCr) levels, and they also had the highest proportion of receiving mechanical ventilation, requiring vasopressor support, and undergoing renal replacement therapy (RRT), all P < 0.01. Of these 3 107 patients, 1 584 (51.0%) were diagnosed with AKI, and the incidence of AKI in patients with sepsis was significantly higher than in those without sepsis [71.2% (653/917) vs. 42.5% (931/2 190), P < 0.01]. The highest proportion of KDIGO 0 stage was observed in the non-sepsis group (57.5%), while the highest proportion of KDIGO 3 stage was observed in the sepsis group (32.2%). Within the same KDIGO stage, the mortality of patients with sepsis was significantly higher than that of non-sepsis patients (0 stage: 17.8% vs. 3.1%, 1 stage: 36.3% vs. 7.4%, 2 stage: 42.7% vs. 17.1%, 3 stage: 54.6% vs. 28.6%, AKI: 46.1% vs. 14.2%). The ICU mortality (38.7%) and in-hospital mortality (46.1%) in the AKI and sepsis group were significantly higher than those in the other three groups. Kaplan-Meier survival curves further showed that the cumulative survival rate of patients with AKI and sepsis during hospitalization was significantly lower than that of the other three groups (53.9% vs. 96.9%, 85.8%, 82.2%, Log-Rank: χ2 = 379.901, P < 0.001). Subgroup analysis showed that among surviving patients, length of ICU stay and total length of hospital stay were significantly longer in the AKI and sepsis group than those in the other three groups (both P < 0.01). Multivariate regression analysis showed that age, APACHEⅡscore and SOFA score within 24 hours of ICU admission, coronary heart disease, AKI, sepsis, and AKI combined with sepsis were independent risk factors for ICU mortality in patients (all P < 0.05). After adjusting for covariates, AKI, sepsis, and sepsis combined with AKI were significantly associated with higher ICU and in-hospital mortality, with the highest ICU mortality [adjusted odds ratio ( OR) = 14.82, 95% confidence interval (95% CI) was 8.10-27.12; Hosmer-Lemeshow test: P = 0.816] and in-hospital mortality (adjusted OR = 7.40, 95% CI was 4.94-11.08; Hosmer-Lemeshow test: P = 0.708) observed in patients with sepsis combined with AKI. Conclusions:The incidence of AKI is high in sepsis patients, and those with both AKI and sepsis have a higher disease burden, more abnormalities in physiological and laboratory indicators, and significantly increased ICU and in-hospital mortality. Among surviving patients, the length of ICU stay and total length of hospital stay are also longer in the AKI and sepsis group. Age, APACHEⅡscore and SOFA score within 24 hours of ICU admission, coronary heart disease, AKI, and sepsis are independent risk factors for in-hospital mortality in ICU patients.
		                        		
		                        		
		                        		
		                        	
4.Prospect effect of music therapy on mental state and its application in manned spaceflight
Ziqing CAO ; Haibo QIN ; Yanlei WANG ; Feng LIU ; Xiang ZHANG ; Meiping GAO ; Bin WU
Space Medicine & Medical Engineering 2024;35(4):245-251
		                        		
		                        			
		                        			As China's manned space missions gradually develop towards long-term residence and deep space exploration,astronauts will face increasingly severe psychological challenges.As a psychological adjustment method involving multiple disciplines such as music,psychology,and medicine,music therapy has the advantages of being convenient to implement,cost-effective,and highly personalized.This paper integrates the concept of music therapy and explores the research progress of music therapy in regulating psychological states in aspects such as physiology,emotional regulation,cognitive ability,and interpersonal relationships.Combined with the mechanism of action of music therapy and the practical situation in the field of manned spaceflight,it aims at the future development trends and problems to be solved,to construct a music therapy system for astronauts during on-orbit flight and ground daily training.This will help astronauts achieve healthy physical and mental development and promote the completion of missions.
		                        		
		                        		
		                        		
		                        	
5.Characteristics of response to joint attention under diverse guiding behaviors in preschoolers with moderate to se-vere autism spectrum disorder
Xuling HAN ; Hang ZHAO ; Mudi SUN ; Meiping ZHAO ; Yanxia WANG ; Min LIU ; Lu QU ; Qiaoyun LIU
Chinese Journal of Rehabilitation Theory and Practice 2024;30(8):882-887
		                        		
		                        			
		                        			Objective To explore the characteristics of response to joint attention(RJA)under diverse guiding behaviors for pre-schoolers with moderate to severe autism spectrum disorder(ASD). Methods From March to May,2023,21 children with moderate to severe ASD and 16 children with developmental de-lays matched the physiological ages were selected from Jiaxing Sunlight Rehabilitation Kindergarten,and 16 typ-ical developmental children matched the physiological ages were selected from the kindergartens nearby.They accepted a behavioral experiment on RJA.The number of RJA,frequence of RJA and the coefficient of variation of guiding behaviors needed to RJA were compared among the three groups. Results About half of the ASD group responded after guiding of head-turning,and the others required higher levels of guiding.The frequence of RJA after guiding of head-turning was less in the ASD group than in the typical devel-opment group(χ2>6.170,P<0.05),and the coefficient of variation of guiding behaviors was more(d=4.039,P<0.001). Conclusion Preschoolers with moderate to severe ASD are able to respond to joint attention,and this ability is poorer than typically developing children.The guiding behavior of the evaluator should be considered in assessing and intervening RJA in preschoolers with ASD.
		                        		
		                        		
		                        		
		                        	
6.Differences of clinical characteristics between temporal lobe epilepsy with bilateral hippocampal sclerosis and temporal lobe epilepsy with unilateral hippocampal sclerosis
Qi TAO ; Chenmin HE ; Jingjing QIU ; Yuyu YANG ; Sha XU ; Yi GUO ; Hong LI ; Yao DING ; Meiping DING ; Shuang WANG
Chinese Journal of Neuromedicine 2024;23(5):450-457
		                        		
		                        			
		                        			Objective:To compare the differences of clinical characteristics of temporal lobe epilepsy with bilateral hippocampal sclerosis (TLE-bHS) with those of temporal lobe epilepsy with unilateral hippocampal sclerosis (TLE-uHS).Methods:A retrospective analysis was performed. Forty-eight patients with confirmed TLE-bHS enrolled in Epilepsy Center, Department of Neurology, Second Affiliated Hospital, Medical School of Zhejiang University from January 2013 to January 2022 were chosen, and 101 patients with confirmed TLE-uHS admitted to our hospital at the same time period were selected as controls. Clinical data such as onset age, disease course, past medical history, seizure frequency, anti-seizure medications, video EEG and neuropsychological test results, and outcomes were analyzed.Results:Compared with the TLE-uHS group, the TLE-bHS group had higher male proportion, elder onset age, shorter disease course, higher seizure frequency, more types of past and currently used anti-seizure medications, lower proportion of autonomic nerve with aura, higher proportion of no aura at onset, higher proportion of slow head background movement in video EEG, and lower memory quotient, verbal memory scores and non-verbal memory scores, with significant differences ( P<0.05); the differences in ratio of past medical history and ratio of distributions of regions with interictal epileptiform abnormalities between the 2 groups were statistically significant ( P<0.05): the TLE-bHS group had significantly higher proportion of previous intracranial infection/encephalitis and higher ratio of bilateral temporal epileptiform abnormalities than the TLE-uHS group, while the TLE-uHS group had significantly higher proportion of patients with febrile convulsion history and higher ratio of unilateral temporal epileptiform abnormalities ( P<0.05). Only 10 patients (20.8%) in the TLE-bHS group received non-drug therapy, including anterior temporal lobectomy in 3 patients (Engel grading I in postoperative follow-up for 2 years), neuroregulatory therapy in 4, and ketogenic diet in 4; of the 55 patients (54.5%) in the TLE-uHS group who underwent anterior temporal lobectomy, 48 patients (87.3%) had Engel grading I, 1 patient (1.8%) had grading II, 4 (7.3%) had grading III, and 2 (3.6%) had grading IV after 2 years of follow-up. Conclusion:Differences in onset age, disease course, past medical history, seizure frequency, anti-seizure medications, and video EEG and neuropsychological test results can help to discriminate patients with TLE-bHS or with TLE-uHS.
		                        		
		                        		
		                        		
		                        	
7.Kinematic and Dynamic Study on Traditional Chinese Cervical Manipulation
Meiping TONG ; Huihao WANG ; Hongsheng ZHAN ; Fuwei PAN ; Yisong WANG ; Yupeng WANG
Journal of Medical Biomechanics 2023;38(1):E065-E070
		                        		
		                        			
		                        			 Objective To simultaneously collect and analyze the kinematic and dynamic parameters for two techniques of traditional Chinese cervical manipulation ( TCCM), and quantitatively describe its biomechanical characteristics. Methods A senior practitioner completed the TCCM (positioning and directional rotation pulling, lateral flexion, respectively) on 10 healthy subjects, and the fluorescent marker balls were pasted on the operator to capture manipulation movements. The dynamic parameters and the surface electromyography ( sEMG) signals were collected by pressure-sensitive gloves and wireless sEMG acquisition system. Results The upper arm muscle was the main force muscle during TCCM, and biceps brachii had the highest contribution rate. The range of motion (ROM), speed, pulling force, and time during cervical spine positioning and directional rotation pulling were all greater than those during cervical spine lateral flexion. The integrate electromyography ( iEMG) and root mean square (RMS) for each muscle of the operator during cervical spine positioning and directional rotation pulling were higher than those during cervical spine lateral flexion. Conclusions The overall ROM, three-dimensional (3D) motion angle, load intensity and time during CCTM have the characteristics of high speed, low amplitude and strong force, reflecting the biomechanical characteristics of ‘ cunjin ’ ( one-inch punch ) in traditional Chinese medicine. This study provides references for further standardizing manual teaching and training and improving clinical safety. 
		                        		
		                        		
		                        		
		                        	
8.Clinical effects of plantar split-thickness skin grafts in repairing the deep burn wounds in the back and buttocks
Shurun HUANG ; Huiqiang SU ; Yiyong WANG ; Jiangtao LIU ; Yong ZHANG ; Bo ZHOU ; Meiping ZHUANG
Chinese Journal of Burns 2023;39(4):371-375
		                        		
		                        			
		                        			Objective:To explore the clinical effects of plantar split-thickness skin grafts in repairing the deep burn wounds in the back and buttocks.Methods:A retrospective observational study was conducted. From January 2011 to February 2022, 98 patients with deep burn who met the inclusion criteria were admitted to the 910 th Hospital of Joint Service Support Unit of PLA, including 64 males and 34 females, aged 17 to 78 years, with total burn areas of 35%-95% total body surface area (TBSA). The area of full-thickness burns in the back and buttocks ranged from 5% to 17% TBSA and the wounds were repaired only using stamp-shaped split-thickness skin grafts from plantar areas of both feet or combined with Meek microskin grafts or stamp-shaped skin grafts from other sites. According to the times of skin graft harvesting from both soles, these patients were divided into one-harvesting group (29 cases), two-harvesting group (38 cases), three-harvesting group (21 cases), and four-harvesting group (10 cases). The area of skin grafts harvested each time from both soles, the healing time of donor sites after each skin graft harvesting, and the survival rate of plantar skin graft in recipient site at 7 days after each skin graft harvesting in 98 patients, the interval between two adjacent skin graft harvesting in 69 patients with skin grafts harvested twice or more, as well as the healing time of donor site and survival rate of skin graft in recipient site after the last skin graft harvesting from both soles of patients in the 4 groups were recorded. The patients were followed up to observe the appearance, texture, and scar in recipient site of plantar skin grafts as well as the scar and function in plantar donor sites. Data were statistically analyzed with one-way analysis of variance, Kruskal-Wallis test, and chi-square test. Results:In the 98 patients, the area of skin graft was 2.0%-4.5% ((3.4±0.6)%) TBSA harvested each time from both soles, the healing time of donor site after each skin graft harvesting was 7-10 (7.8±1.1) d, and the survival rate of plantar skin graft in recipient site at 7 days after each skin graft harvesting was 93% (92%, 95%). The interval between two adjacent skin graft harvesting in the 69 patients was 7-38 (11.2±0.5) d. The healing time of donor site and survival rate of skin graft in recipient site after the last skin graft harvesting from both soles of patients in the 4 groups showed no statistically significant differences ( P>0.05). A total of 88 patients were followed up for 3 months to 5 years, the appearance in recipient site of plantar skin graft was smooth, the texture was firm, the scar hyperplasia was mild, and the area was compressive- and wear-resistant. Among them, the plantar donor site recovered well in 85 patients, without obvious scar hyperplasia and only 3 patients had small area of scar hyperplasia in the non-weight-bearing areas which did not affect walking or wearing shoes or socks. Ten patients were lost in the follow up after discharge. Conclusions:Stamp-shaped split-thickness skin grafts can be repeatedly harvested from both soles of patient to repair the deep burn wounds in the back and buttocks, with high survival rate of skin grafts, thus can reduce the burden of other donor sites. Moreover, the skin grafts have good wear-resistance and pressure-resistance, without affecting postoperative normal walk.
		                        		
		                        		
		                        		
		                        	
9.Two case reports of X-linked acrogigantism and pathogenic gene detection
Hanting LIANG ; Fengying GONG ; Zhihui LIU ; Yingying YANG ; Yong YAO ; Renzhi WANG ; Linjie WANG ; Meiping CHEN ; Hui PAN ; Bo CHEN ; Zhiyong LIANG ; Feng FENG ; Huijuan ZHU
Chinese Journal of Endocrinology and Metabolism 2022;38(2):118-124
		                        		
		                        			
		                        			Objective:To report the clinical characteristics, diagnosis, and treatment of 2 cases of X-linked acrogigantism(X-LAG).Methods:The clinical information of two patients were retrospectively reported, and peripheral blood DNA was collected for copy number variations detection.Results:Both patients had onset at age of two, with common clinical characteristics including linear growth acceleration, mild facial coarsening, enlargement of hands and feet, increased appetite, and snoring, etc. The heights Z scores of the two patients before treatment were + 6.86 and + 6.53, respectively. Growth hormone(GH) glucose inhibition test showed that GH nadir values were over 1 ng/mL and insulin-like growth factor-Ⅰ(IGF-Ⅰ) were 586.0 ng/mL and 1 042.0 ng/mL, respectively. Patient 1 received three cycles of octreotide microspheres therapy followed by surgery, and achieved clinical and biochemical remission. Patient 2 had lanreotide for 5.5 years but failed biochemical remission. Microduplication of Xq26.3, which contained pathogenic gene G-protein coupled receptor 101(GPR101), was found in germline DNA of two patients through copy number variation detection, leading to the diagnosis of X-LAG.Conclusion:It should be cautious of X-LAG when children below 2 years old presents symptoms such as overgrowth and so on. Medication combined with surgery is effective.
		                        		
		                        		
		                        		
		                        	
10.Value of octreotide suppression test in predicting the efficacy of long-acting somatostatin receptor ligands in pituitary GH adenomas
Ran LI ; Lian DUAN ; Hui PAN ; Shengmin YANG ; Linjie WANG ; Hongbo YANG ; Fengying GONG ; Xiaoan KE ; Meiping CHEN ; Huijuan ZHU
Chinese Journal of Endocrinology and Metabolism 2022;38(4):288-293
		                        		
		                        			
		                        			Objective:To explore the value of octreotide suppression test(OST) in predicting the efficacy of somatostatin receptor ligands(SRLs) in the treatment of active acromegaly.Methods:The clinical data of 76 patients with active acromegaly from 2011 to 2020 was retrospectively analyzed. OST was carried out as follows: After an overnight fasting and baseline sampling of growth hormone(GH), 100 μg octreotide was subcutaneously injected, and sampling for GH was obtained every 2 hours for 8 hours. All patients were treated with SRLs for at least 3 months. A good GH response is defined as a post-treatment random GH<1 μg/L or >80% fall compared with the baseline GH. A good insulin-like growth factor Ⅰ(IGF-Ⅰ) response is defined as IGF-Ⅰ<1.3 upper limit of normal(ULN) or >50% reduction compared with the baseline. If both GH and IGF-Ⅰ fulfill the criteria of a good response, it is defined as a good GH and IGF-Ⅰ response.Results:The baseline level of GH during OST was 15.00(6.38, 34.20) μg/L, the median time to reach the nadir GH was(3.65±1.65) hours, and the nadir GH level was 1.47(0.50, 4.19) μg/L. The median GH suppression rate was 89.12%(72.71%, 95.09%). When the cutoff value of GH suppression rate in predicting a good GH response was 89.32%, the area under the curve(AUC) was 0.74, with a sensitivity of 81.80% and specificity of 66.00%. When the cutoff value of GH suppression rate in predicting a good IGF-Ⅰ response was 93.14%, the AUC was 0.64, with a sensitivity of 50.00% and specificity of 75.60%. When the GH suppression rate was 90.71%, the AUC was 0.78, with the sensitivity of 83.30% and specificity of 70.00% in predicting a good GH and IGF-Ⅰ response. Compared with GH/IGF-Ⅰ non-responders, GH/IGF-Ⅰ responders displayed lower nadir GH during OST, higher GH suppression rate and IGF-Ⅰ reduction rate, and lower ratio of IGF-1 to ULN( P<0.05). Conclusion:GH suppression rate during the OST is a valuable predictor to evaluate the efficacy of SRLs in patients with acromegaly, with the highest sensitivity and specificity when the cutoff value is 90.71%.
		                        		
		                        		
		                        		
		                        	
            
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