1.Effect of Tongnao Yizhi Formula (通脑益智方) on Cognitive Function and Gut Microflora in Treating Vascular Cognitive Impairment No Dementia Patients with Spleen and Kidney Depletion,Phlegm and Stasis Obstructing Collaterals Syndrome
Xiwu YAN ; Jiaoyang KANG ; Ting MENG ; Jinfeng LIU ; Yinglong LAI ; Yiwei ZHU ; Cheng CHANG
Journal of Traditional Chinese Medicine 2024;65(13):1353-1362
		                        		
		                        			
		                        			ObjectiveTo observe the clinical efficacy and mechanism of Tongnao Yizhi Formula (通脑益智方, TYF) in treating vascular cognitive impairment no dementia (VCIND) with spleen and kidney depletion, phlegm and stasis obstructing collaterals syndrome. MethodsNinety-two VCIND patients with spleen and kidney depletion, phlegm and stasis obstructing collaterals syndrome were randomly divided into control group (42 cases) and treatment group (52 cases). Both groups received routine basic treatment. The control group was given donapezil hydrochloride capsules orally, 5 mg each time, once at night, while the treatment group was given TYF orally, 1 dose per day. Both groups were treated continuously for 3 months. The scores of Mini-Mental State Examination (MMSE), Vascular Dementia Assessment Scale-Cognitive Subscale (VaDAS-Cog), Activity of Daily Living Scale (ADL), and TCM syndrome scores (the primary symptoms such as sluggish thinking, forgetfulness, temperament changes, and language confusion, and secondary symptoms such as weakness of waist and knees, dizziness and headache, occasional tinnitus, fatigue, heaviness of limbs, insomnia and irritability, poor appetite and abdominal distension, numbness of face) were observed before and after treatment in both groups. The changes in gut microflora diversity and flora abundance structure as well as fecal short-chain fatty acids (SCFAs) levels including acetic acid, propionic acid, butyric acid, isobutyric acid, isovaleric acid, valeric acid, and caproic acid were compared between groups. The feces of 20 healthy subjects in the same period were included as reference. Safety was evaluated during the study. ResultsAfter treatment, both groups exhibited significant increases in MMSE scores and decreases in VaDAS-cog scores (P<0.05 or P<0.01), and ADL scores in the treatment group significantly increased (P<0.05). Scores of symptoms including sluggish thinking, forgetfulness, temperament change, language confusion, heaviness of limbs, insomnia, irritability, poor appetite, abdominal distension, and facial numbness as well as the total score significantly decreased in both groups after treatment (P<0.05 or P<0.01). When compared between groups, the treatment group showed substantial reductions in scores of weakness of waist and knees, tinnitus, fatigue, heaviness of limbs, insomnia, irritability, loss of appetite and abdominal distension (P<0.05 or P<0.01). The gut microflora diversity analysis showed that the Shannon index of the treatment group significantly increased after treatment (P<0.05).PCoA analysis and ANOSIM test indicated significant differences between groups, suggesting changes in microflora species (P<0.01). After treatment, the relative abundance of Bacteroidetes and Fusobacteria in the treatment group increased, while the relative abundance of Actinobacteria, Verrucomicrobia and Cyanobacteria decreased (P<0.05); the relative abundance of Faecalibacterium prausnitzii, Bifidobacterium, Lactobacillus, and Ruminococcus increased significantly (P<0.05). Compared to the the gut microflora species diversity of the healthy people, it is indicated that the gut microflora structure in the treatment group was close to that of the healthy people, while there was no such trend in the control group. In the treatment group, acetic acid, propionic acid, and butyric acid in the treatment group were all higher after treatment (P<0.05 or P<0.01). ConclusionsTYF can improve the cognitive ability and quality of life of VCIND patients with spleen and kidney depletion, phlegm and stasis obstructing collaterals syndrome, and this improvement may be related to regulating intestinal microecology. 
		                        		
		                        		
		                        		
		                        	
2.Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB
Liu YANG ; Yu Shi WANG ; Ting Ting JIANG ; Wen DENG ; Min CHANG ; Ling Shu WU ; Hua Wei CAO ; Yao LU ; Ge SHEN ; Yu Ru LIU ; Jiao Yuan GAO ; Jiao Meng XU ; Ping Lei HU ; Lu ZHANG ; Yao XIE ; Hui Ming LI
Biomedical and Environmental Sciences 2024;37(3):303-314
		                        		
		                        			
		                        			Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.
		                        		
		                        		
		                        		
		                        	
3.Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury
Hua Wei CAO ; Ting Ting JIANG ; Ge SHEN ; Wen DENG ; Yu Shi WANG ; Yu Zi ZHANG ; Xin Xin LI ; Yao LU ; Lu ZHANG ; Yu Ru LIU ; Min CHANG ; Ling Shu WU ; Jiao Yuan GAO ; Xiao Hong HAO ; Xue Xiao CHEN ; Ping Lei HU ; Jiao Meng XU ; Wei YI ; Yao XIE ; Hui Ming LI
Biomedical and Environmental Sciences 2024;37(5):494-502
		                        		
		                        			
		                        			Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.
		                        		
		                        		
		                        		
		                        	
4.Analysis of Correlation Between the Occurrence of Seasonal Allergic Rhinitis in Ren-Yin Stem-Branch Year of Chinese Lunar Calendar and Innate Circuit Qi Endowment of the Patients
Zhao-Qian WANG ; Xiang-Ting MA ; Chang GAO ; Ting-Ting CAI ; Zhi-Han CHEN ; Jing LIU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(5):1116-1122
		                        		
		                        			
		                        			Objective To analyze the innate circuit qi endowment of patients with seasonal allergic rhinitis(SAR)in Renyin year(Ren-Yin stem-branch year of Chinese lunar calendar).Methods A retrospective study was conducted in 8 918 SAR patients who were treated in the Department of Otorhinolaryngology of Xiyuan Hospital,China Academy of Chinese Medical Sciences in pollen seasons of the spring and autumn(i.e.,the period of March 5 to May 21,and the period of August 7 to September 23)in 2022(Renyin year).The characteristics of circuit qi at birth date of the SAR patient were analyzed.Results The occurrence of SAR in Renyin year was related to the suiyun(yearly circuit phase),sitian(the first half of the alterable yearly circuit qi),dominant qi,and circuit qi combination.The two-factor model analysis showed that the occurrence of SAR in Renyin year was closely related with suiyun-sitian and dominant qi-guest qi.High morbidity of SAR was shown in the patients born in the year of heavenly-stem Ren and earthly-branch Xu,and with the circuit qi features of five circuits being wood circuit,Suiyun being excessive wood circuit,sitian of yangming dryness-gold,zaiquan(the second half of the alterable yearly circuit qi)of shaoyin monarch-fire,dominant qi being yangming dryness-gold,and circuit qi combination being disharmony.The two-factor model analysis showed that the morbidity of SAR was increased in the year with the circuit qi features of suiyun-sitian being excessive wood circuit and taiyang cold-water,and the combination of dominant qi and guest qi being yangming dryness-gold and taiyang cold-water.Conclusion Among the innate circuit qi factors,suiyun,sitian,dominant qi,and circuit qi combination have an impact on the occurrence of SAR.The interaction between innate circuit qi and circuit qi at onset may be one of the important mechanisms leading to the occurrence of SAR.
		                        		
		                        		
		                        		
		                        	
5.Effect of XUE Ji's Morning-Evening Supplementing Method Combined with Seretide on Exercise Endurance in Patients with Stable Chronic Obstructive Pulmonary Disease of Lung and Kidney Deficiency Type
Qian SU ; Chang LI ; Ting LEI ; Yuan LIU ; Xuan-Er LONG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(6):1430-1437
		                        		
		                        			
		                        			Objective To investigate the effect of XUE Ji's morning-evening supplementing method,a therapy by tonification according to the alteration of daily yang-qi in the human body and the nature proposed by practitioner XUE Ji in Ming Dynasty,combined with Seretide on exercise endurance in patients with stable chronic obstructive pulmonary disease(COPD)of lung and kidney deficiency type.Methods Ninety-two patients with stable COPD of lung and kidney deficiency type were randomly divided into treatment group and control group,with 46 cases in each group.The control group was given inhalation of Salmeterol/Fluticasone Inhalation Powder(Seretide),and the treatment group was treated with Buzhong Yiqi Pills in the morning and Liuwei Dihuang Pills at evening on the basis treatment for the control group.The course of treatment covered 3 months.The changes of the scale scores of traditional Chinese medicine(TCM)syndrome and St Georges respiratory questionnaire(SGRQ)for quality of life,the distance of 6-minute walking test(6MWT)for exercise endurance,and pulmonary function indicators of forced expiratory volume in one second(FEV1),forced vital capacity(FVC)and their ratio(FEV1/FVC)in the two groups before and after treatment were observed.After treatment,the clinical efficacy and the incidence of adverse reactions were compared between the two groups.Results(1)During the trial,a total of 3 cases were lost,and a total of 89 patients were eventually included,including 45 cases in the treatment group and 44 cases in the control group.(2)After 3 months of treatment,the total effective rate of the treatment group was 82.22%(37/45),and that of the control group was 72.73%(32/44).The intergroup comparison by chi-square test showed that the efficacy of the treatment group was significantly superior to that of the control group(P<0.05).(3)After treatment,the scores of TCM syndromes in the two groups were significantly decreased compared with those before treatment(P<0.01),and the decrease in the treatment group was more significant than that in the control group(P<0.01).(4)After treatment,the lung function indicators of FEV1,FVC and FEV1/FVC in the two groups were significantly improved compared with those before treatment(P<0.05),and the improvement in the treatment group was significantly superior to that in the control group(P<0.05).(5)After treatment,the scores of SGRQ items of respiratory symptoms,disease impact and activity limitation in the two groups were significantly lower than those before treatment(P<0.01),and the decrease in the treatment group was significantly superior to that in the control group,the differences being statistically significant(P<0.01).(6)After treatment,the 6MWT distance of the two groups was significantly improved compared with that before treatment(P<0.01),and the improvement in the treatment group was significantly superior to that in the control group(P<0.01).(7)During the treatment,no abnormal changes in the indicators of blood routine test,liver and kidney function,electrocardiogram,and urine and stool routine were found in the two groups.Conclusion XUE Ji's morning-evening supplementing method combined with Seretide exert certain effect in treating stable COPD patients with lung and kidney deficiency syndrome.The therapy can effectively alleviate the clinical symptoms ofnd improve the lung function,exercise endurance and quality of life of the patients,with high safety.
		                        		
		                        		
		                        		
		                        	
6.Histopathological changes in secondary visual cortex and enhanced calcium activity in neurons being involved in microwave radiation-induced anxiety-like behavior
Zhihua FENG ; Ting PAN ; Ganghua HE ; Chenxu CHANG ; Zhilin CUI ; Meiying YANG ; Yanhui HAO ; Fengsong LIU ; Yang LI ; Hongyan ZUO
Chinese Journal of Radiological Medicine and Protection 2024;44(6):464-471
		                        		
		                        			
		                        			Objective:To clarify the effects of microwave radiation on anxiety-like behavior, the histomorphology of the secondary visual cortex, and calcium activity in neurons.Methods:36 C57BL/6N mice were selected and divided into control group and microwave radiation group according to the random number table method. In the simple behavioral testing, there were 8 mice in the control group and 7 mice in the radiation group. Combining fiber optic recording with behavioral experiments, there were 8 mice in the control group and 7 mice in the radiation group. Hematoxylin-eosin (HE) staining was conducted with 3 mice in each group. A high-power microwave simulated source in the X-band with a center frequency of 9.875 GHz and an average power density of 12 mW/cm 2 was used to irradiate the mice for 15 minutes, establishing a microwave radiation animal model. Then, anxiety-like behavior changes in the radiation group were identified using the open-field and elevated plus maze (EPM) tests. The effects of microwave radiation on the histomorphology of the secondary visual cortex were investigated using HE staining and optical microscopy. Based on the genetically encoded calcium imaging technique, as well as optical fiber recording combined with behavioral paradigms in the open field and the EPM, the changes of calcium activity in neurons in the V2M region of the secondary visual cortex were detected. Results:Compared to the control group, the radiation group showed a significant decrease in the frequency of exploring the central region of the open field and the open arm of the EPM ( t = 2.24, 3.10, P < 0.05). Furthermore, the radiation group exhibited the degeneration and apoptosis of some neurons in the secondary visual cortex, primarily manifested as pyknosis and deep staining, cell body shrinkage, and the slightly widening of perivascular space. Fiber optic recordings and behavioral experiments indicated that compared to the control group, mice in the radiation group exhibited significantly increased calcium activities in neurons of the secondary visual cortex when exploring the central region of the open field ( t = -2.75, P < 0.05) or the open arm of the EPM ( t = -2.77, -3.41, P < 0.05) compared to those before radiation after microwave exposure. Conclusions:Microwave radiation can induce anxiety-like behaviors and histopathological changes in the secondary visual cortex. Increased calcium activity in neurons of the secondary visual cortex is proved to be an important mechanism underlying the changes in anxiety-like behavior due to microwave radiation.
		                        		
		                        		
		                        		
		                        	
7.Investigation and analysis of nursing management in Operating Rooms of 2 201 hospitals in China
Xiangqi MI ; Li GUO ; Xinglian GAO ; Li HE ; Mei XU ; Ling SONG ; Guohong LI ; Xiaomin CHEN ; Houchan CHANG ; Li LI ; Ting LIU ; Li MU
Chinese Journal of Modern Nursing 2024;30(13):1688-1697
		                        		
		                        			
		                        			Objective:To understand the current status of human resources in Operating Room nursing in China, so as to provide reference for nursing management, human resource allocation, nursing education and training in Operating Rooms.Methods:Using the stratified sampling method, a self-made Operating Room nursing human resource survey questionnaire of Chinese Nursing Society was used as a research tool in July 2021 to investigate the general situation, surgical workload, human resource allocation, Operating Room management, Operating Room information construction, nursing education and training of 2 201 hospitals in 31 provinces, autonomous regions and municipalities of China.Results:Among the 2 201 hospitals, there were 1 021 tertiary hospitals (46.39%), 1 177 secondary hospitals (50.75%), and 63 primary and below hospitals (2.86%). There were 2 056 hospitals with less than 30 Operating Rooms, accounting for 93.41%. There were 1 991 hospitals with an annual number of surgical cases less than 20 000, accounting for 90.46%, the educational background of Operating Room nurses was mainly undergraduate (66.93%, 43 359/64 780), with a total of 67.99% (44 045/64 780) having a bachelor's degree or above. Nurses were the main professional titles (42.66%, 27 632/64 780). Number of Operating Rooms: the number of Operating Room nurses (median) was 1: 2.43 and 78.96% (1 738/2 201) of hospital operating theatres were managed by Nursing Departments or hospitals. A total of 1 479 hospitals (67.20%) established anesthesia recovery rooms in their Operating Rooms, which was higher than 59.34% (1 210 hospitals) surveyed in 2016, and the difference was statistically significant (χ 2=226.701, P<0.01). 74.69% (1 644/2 201) and 87.87% (1 934/2 201) of hospitals carried out post management and capacity classification management in Operating Rooms, respectively. Day surgery and robotic surgery were performed in 47.80% (1 052/201) and 7.68% (169/2 201) hospitals, respectively. 36.98% (814/2 201) of the hospitals passed the information evaluation system certification and 64.61% (1 422/2 201) of the hospitals used the Operating Room information management system. In the Operating Room information system of the hospital, 2.54% (56/2 201) had intelligent functions. And 77.24% (1 700/2 201) of hospitals participated in the qualification training of Operating Room specialist nurses. Conclusions:By July 2021, the number of Operating Rooms in most hospitals in China is less than 30, and the annual number of operating cases is less than 20 000. The educational background and professional title of Operating Room nurses are mainly undergraduate and nurse. More than 60% of hospitals have set up anesthesia recovery rooms and have information management systems for Operating Rooms. At the same time, Operating Rooms in Chinese hospitals have widely implemented diversified nursing management models such as post management and ability grading management.
		                        		
		                        		
		                        		
		                        	
8.Status quo of nursing practice and organizational management for reperfusion therapy in ischemic stroke in Beijing
Shanshan ZHANG ; Wenya CAO ; Hong CHANG ; Jie ZHAO ; Qingfeng MA ; Ting YANG ; Gaoting MA ; Mengrao LIU ; Suai LI
Chinese Journal of Modern Nursing 2024;30(27):3744-3749
		                        		
		                        			
		                        			Objective:To investigate the status of nursing practice and organizational management for reperfusion therapy in ischemic stroke across medical institutions in Beijing.Methods:In June 2023, a survey was conducted among nursing managers from 62 medical institutions under the jurisdiction of the Beijing Stroke Treatment Quality Control and Improvement Center. The survey aimed to assess the current nursing practices and organizational management for reperfusion therapy in ischemic stroke.Results:Among the 62 medical institutions, 16.13% (10/62) had dedicated reperfusion therapy nurses for stroke, and 87.10% (54/62) had established specific nursing protocols and procedures for stroke reperfusion therapy within their departments. However, 27.42% (17/62) of these institutions based the development and updates of their protocols on experiential summaries rather than standardized guidelines. In terms of nursing practice, there was room for improvement in emergency identification and triage of suspected stroke patients, assistance with intravenous thrombolysis, patient condition monitoring, early rehabilitation, and related health education. Regarding nursing quality control, significant differences were observed between institutions that regularly conducted quality control of stroke reperfusion therapy nursing and those that organized regular training sessions for nurses in this area ( P<0.05) . Conclusions:While nursing practices and quality for stroke reperfusion therapy in Beijing are progressing, there are disparities in regional development. There is a high demand for specialized stroke nursing and targeted technical training.
		                        		
		                        		
		                        		
		                        	
9.Nutritional status of pediatric patients undergoing allogeneic hematopoietic stem cell transplantation
Mei YAN ; Wei-Bing TANG ; Yong-Jun FANG ; Jie HUANG ; Ting ZHU ; Jin-Yu FU ; Xiao-Na XIA ; Chang-Wei LIU ; Yuan-Yuan WAN ; Jian PAN
Parenteral & Enteral Nutrition 2024;31(5):257-261
		                        		
		                        			
		                        			Objective:To observe the changes in the nutritional status of pediatric patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT)for one year,and to analyze the risk factors.Methods:We collected data from 88 pediatric patients who underwent allo-HSCT at the Department of Hematology and Oncology in Children's Hospital of Nanjing Medical University between May 2018 and November 2022.All pediatric patients underwent nutritional status analysis before transplantation,at enrollment,3 months,6 months and 1 year after allo-HSCT.Linear regression model was used to analyze the risk factors for growth rate.Results:The body mass index Z score(BMI-Z)before allo-HSCT was(0.096±1.349),and decreased to(-0.258±1.438)、(-0.715±1.432)、(-0.584±1.444)at enrollment,3 months,6 months after allo-HSCT,and(-0.130±1.317)at 1 year after allo-HSCT(P<0.001).There was no significant change in BMI-Z between pre-transplantation and 1 year after transplantation(P=1.000).Height for age Z score(HAZ)before transplantation was(0.137±1.305)and decreased to(-0.083±1.267)、(-0.221±1.299)、(-0.269±1.282)in 3 months,6 months and 1 year after allo-HSCT(P<0.001).Multivariate linear regression showed that age≥10 years old(P=0.015)and chronic graft-versus-host disease(cGVHD)(P=0.005)were independent risk factors for change in HAZ.Conclusion:The BMI-Z of pediatric patients treated with allo-HSCT returned to the pre-transplantation level after one year,while HAZ continued to decrease.Allo-HSCT may cause impaired growth rate in pediatric patients.Attention should be paid to HAZ changes in pediatric patients before and after allo-HSCT,especially in pediatric patients≥10 years old of age and those with cGVHD.Effective nutritional intervention should be provided in time.
		                        		
		                        		
		                        		
		                        	
10.Characteristics of drug resistance and biofilm formation in carbapenem-resistant Acinetobacter baumannii in hospitalized children
Yun-Yun LI ; Hou-Chang LIU ; Hai-Ping WANG ; Ting-Yi DU ; Li JIANG
Chinese Journal of Contemporary Pediatrics 2024;26(4):358-364
		                        		
		                        			
		                        			Objective To study the distribution,drug resistance,and biofilm characteristics of carbapenem-resistant Acinetobacter baumannii(CRAB)isolated from hospitalized children,providing a reference for the prevention and treatment of CRAB infections in hospitalized children.Methods Forty-eight CRAB strains isolated from January 2019 to December 2022 were classified into epidemic and sporadic strains using repetitive extragenic palindromic sequence-based polymerase chain reaction.The drug resistance,biofilm phenotypes,and gene carriage of these two types of strains were compared.Results Both the 22 epidemic strains and the 26 sporadic strains were producers of Class D carbapenemases or extended-spectrum β-lactamases with downregulated outer membrane porins,harboring the VIM,OXA-23,and OXA-51 genes.The biofilm formation capability of the sporadic strains was stronger than that of the epidemic strains(P<0.05).Genes related to biofilm formation,including Bap,bfs,OmpA,CsuE,and intI1,were detected in both epidemic and sporadic strains,with a higher detection rate of the intI1 gene in epidemic strains(P<0.05).Conclusions CRAB strains are colonized in the hospital,with sporadic strains having a stronger ability to form biofilms,suggesting the potential for forming new clonal transmissions in the hospital.Continuous monitoring of the epidemic trends of CRAB and early warning of the distribution of epidemic strains are necessary to reduce the risk of CRAB infections in hospitalized children.[Chinese Journal of Contemporary Pediatrics,2024,26(4):358-364]
		                        		
		                        		
		                        		
		                        	
            
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