1.A multicenter epidemiological study of acute bacterial meningitis in children.
Cai Yun WANG ; Hong Mei XU ; Jiao TIAN ; Si Qi HONG ; Gang LIU ; Si Xuan WANG ; Feng GAO ; Jing LIU ; Fu Rong LIU ; Hui YU ; Xia WU ; Bi Quan CHEN ; Fang Fang SHEN ; Guo ZHENG ; Jie YU ; Min SHU ; Lu LIU ; Li Jun DU ; Pei LI ; Zhi Wei XU ; Meng Quan ZHU ; Li Su HUANG ; He Yu HUANG ; Hai Bo LI ; Yuan Yuan HUANG ; Dong WANG ; Fang WU ; Song Ting BAI ; Jing Jing TANG ; Qing Wen SHAN ; Lian Cheng LAN ; Chun Hui ZHU ; Yan XIONG ; Jian Mei TIAN ; Jia Hui WU ; Jian Hua HAO ; Hui Ya ZHAO ; Ai Wei LIN ; Shuang Shuang SONG ; Dao Jiong LIN ; Qiong Hua ZHOU ; Yu Ping GUO ; Jin Zhun WU ; Xiao Qing YANG ; Xin Hua ZHANG ; Ying GUO ; Qing CAO ; Li Juan LUO ; Zhong Bin TAO ; Wen Kai YANG ; Yong Kang ZHOU ; Yuan CHEN ; Li Jie FENG ; Guo Long ZHU ; Yan Hong ZHANG ; Ping XUE ; Xiao Qin LI ; Zheng Zhen TANG ; De Hui ZHANG ; Xue Wen SU ; Zheng Hai QU ; Ying ZHANG ; Shi Yong ZHAO ; Zheng Hong QI ; Lin PANG ; Cai Ying WANG ; Hui Ling DENG ; Xing Lou LIU ; Ying Hu CHEN ; Sainan SHU
Chinese Journal of Pediatrics 2022;60(10):1045-1053
		                        		
		                        			
		                        			Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ2=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Brain Abscess
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			Child, Preschool
		                        			;
		                        		
		                        			Escherichia coli
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hydrocephalus
		                        			;
		                        		
		                        			Infant
		                        			;
		                        		
		                        			Infant, Newborn
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Meningitis, Bacterial/epidemiology*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Streptococcus agalactiae
		                        			;
		                        		
		                        			Streptococcus pneumoniae
		                        			;
		                        		
		                        			Subdural Effusion
		                        			;
		                        		
		                        			beta-Lactamases
		                        			
		                        		
		                        	
2.Analysis of Relationship between Coagulation Function and Blood Transfusion in Patients with Emergency Rescue.
Xin-Fang ZHU ; Yu-Bo WU ; Li-Hui YANG ; Rong XIA ; Jing-Han LIU ; Jiong-Cai LAN
Journal of Experimental Hematology 2018;26(4):1204-1209
OBJECTIVEThrough researching preoperative coagulation function in the case of ABO-identical blood insufficient for emergency rescue transfusion according to recommended programs of special emergency rescue transfusion was carried out, the relationship between volume of blood products and coagulation function was analyzed.
METHODSThe surgical cases of blood transfusion more than 1 600 ml during operation were collected in our hospitals from Aug 2015 to Dec 2016(n=218), these cases were divided into the normal coagulation group(Group A) and abnormal coagulation group(Group B), and the patients of emergency rescue transfusion O type blood group(Group C). The basic information of cases, the infused volume of red blood cell(RBC), virus-inactivated frozen plasma(VIFP), fresh frozen plasma(FFP), cryoprecipitate(C)and platelets(P), prothrombin time(PT), activated partial thromboplastin time(APTT), fibrinogen(FIB)and international normalized ratio(INR)were analyzed, the relationship between volume of blood transfusion and coagulation function were also analysed. At the same time, the efficiency and safety index were compared before and after transfusion. These indexes, such as hemoglobin(Hb), indirect bilirubin(IBiL), direct antiglobulin test(DAT)and irregular antibody were determined at the time-paints of 24 h, 3 d and 7 d after blood transfusion.
RESULTSThe differences of age and blood type between group A and B was not statistically significant(P>0.05). Proportion of A and AB type,transfusion volume of RBC, FFP, C and Plt all were significantly higher in group C (P<0.05). PT, APTT, FIB and INR in group B and C were significantly different(P<0.05), which related with the transfusion volume of RBC, FFP and C(P<0.05). DAT and irregular antibody in every group was all negative before transfusion, No any new irregular antibodies had been detected after transfusion. Hb after blood transfusion was not statistically different before and after transfusion in group C, the IBiL level also was not significantly increased after blood transfusion(P > 0.05). All those showed that emergency rescue transfusion was safe and effective.
CONCLUSIONPreoperative coagulation function is one of factors inflnencing blood products transfusion volume during operation, which also is the basis for evaluating bleeding and blood transfusion. Emergency O type blood and ABO-matched blood transfusions show the same efficiency and safety.
Blood Coagulation ; Blood Coagulation Tests ; Blood Transfusion ; Humans ; Partial Thromboplastin Time ; Prothrombin Time
3.Experimental Study on Neonatal ABO or RhD Compatible Blood Transfusion.
Wei LIU ; Ai-Ping LE ; Jing-Han LIU ; Jiong-Cai LAN
Journal of Experimental Hematology 2017;25(3):916-920
OBJECTIVETo investigate the safety and effectiveness of neonatal ABO or Rh(D) by using compatible blood transfusion through retrospective analysis of data from cases received compatible blood transfusion and type matched blood transfusion.
METHODSThe clinical data of 26 cases of neonatal compatible blood transfusion in Chinese Nanchang area from January 2014 to October 2016 were collected, and 26 cases of neonatal type-matched blood transfusion were selected according to ratio of 1:1 cases. The efficiency and safety index of 26 patients compatible blood transfusion were compared with that of type-matched blood transfusion. The efficiency indexes included: patients' basic characteristics, red blood cell (RBC) count, hemoglobin (Hb) level, hematocrit (Hct), and the safety indexes contain Hb level and indirect bilirubin (IBiL) value before and after blood transfusion, irregular antibody screening, direct antiglobulin test (DAT) results and the adverse reactions of blood transfusion.
RESULTSThe age, sex, days of hospitalization between compatible blood transfusion and type matched blood transfusion were not statistically significantly different (P>0.05). The Hb level before transfusion, blood transfusion volume and the increase of Hb, Hct and RBC were not statistically significantly different between two groups (P>0.05). The values of Hb, Hct and RBC in 2 groups significantly increased at the day 1 after blood transfusion (P<0.05). No blood transfusion adverse reaction occurred in 2 groups. The IBiL value significantly decreased in compatible blood transfusion patients at the day 1 after blood transfusion (P<0.05). No new irregular antibodies had been detected after transfusion in all patients, and the others' DAT and screening for irregular antibodies were negative except 22 patients with neonatal hemolysis. The values of Hb and IBiL statistically significantly differenence were not in 12 patients between 1d, 3d, 7d after blood transfusion (P>0.05).
CONCLUSIONThe efficiency and safety between compatible blood transfusion and type matched blood transfusion are the same in neonatal blood transfusion. Compatible blood transfusion is a safe and effective in clinical blood transfusion.
4.Study on RHCE genotyping of Rh blood group in Uygur nationality of Xinjiang in China.
Xu-Hua BAI ; Jiong-Cai LAN ; Xiao-Yan GONG ; Li CUI ; Hua-You ZHOU
Journal of Experimental Hematology 2010;18(5):1335-1337
		                        		
		                        			
		                        			This study was aimed to investigate the characteristics of RHCE genotyping of Xinjiang Uygur nationality population in China. Primers for detecting RHCE genes were designed according to the references, 89 Uygur nationality RhD-negative samples, 233 Han nationality RhD-negative samples and 109 Han nationality RhD-positive samples were detected by sequence-specific primer-polymerase chain reaction (SSP-PCR) for RHCE genotyping. All above-mentioned samples were unrelated. The results indicated that RHE/e genotyping results were consistent with the serological test results in the samples of Uygur and Han nationality, regardless of the RhD-negative samples or the RhD-positive samples. The RHC/c genotyping results from 89 RhD-negative samples of Uygur nationality were consistent with serological test results. However, total error of RHC/c genotyping from 233 RhD-negative and 109 RhD-positive samples of Han nationality was 5.05%. In conclusion, this method of RHCE genotyping is suitable for the analysis of the RHE/e genotyping of Uygur nationality, no erroneous RHC/c genotyping of Uygur nationality was found in this study, but this method needs to be further studied.
		                        		
		                        		
		                        		
		                        			Blood Grouping and Crossmatching
		                        			;
		                        		
		                        			China
		                        			;
		                        		
		                        			Ethnic Groups
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Genotype
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Polymorphism, Genetic
		                        			;
		                        		
		                        			Rh-Hr Blood-Group System
		                        			;
		                        		
		                        			genetics
		                        			
		                        		
		                        	
5.Comparison between genotyping and serological phenotyping in RhCE blood group.
Hua-you ZHOU ; Yin-ze ZHANG ; Qing-bao MENG ; Xu-hua BAI ; Cong-rong WANG ; Qiong CAO ; Jiong-cai LAN
Chinese Journal of Medical Genetics 2008;25(1):66-69
OBJECTIVETo genotype the RHCE gene of Hans, Xinjiang's Uigurs and Kazakstans in China, and to compare the results of RHCE genotyping with that of RhCc/Ee phenotyping.
METHODSRHCE genes of 98 Hans with RhD positive and 230 Hans, 72 Uigurs and 18 Kazakstans with RhD/RHD negative were genotyped with PCR-sequence specific primer (SSP) technique.
RESULTSThe results of RHE/RHe genotyping from samples with RhD positive and negative were in accord with that of phenotyping. It would result in 4.44% error using C-->G polymorphism at nt48 of RHCE gene to genotype RHCE, and 4.05% failure of detection using the 109 bp insertion to detectRHCE gene in Chinese Hans. The results of RHE/RHe genotyping in unrelated 72 Uigurs and 18 Kazakstans with RhD phenotype were consistent with that of phenotyping, and false positive and false negative were not found in genotyping in Uigurs and Kazakstans tested.
CONCLUSIONThe results of RHE/RHe and RHc genotyping were correct with PCR-SSP and accordant with that of phenotyping. Using the C48G polymorphism in exon 1 of RHCE to genotype RHC gene would result in false positive resulting from RHc mutation at this locus, and using the 109 bp insertion to genotype RHC gene would result in false negative because of the absence of the 109 bp. Therefore it is necessary to genotype RHC gene using more than two polymorphic loci.
Ethnic Groups ; genetics ; Genotype ; Humans ; Phenotype ; Polymorphism, Genetic ; Rh-Hr Blood-Group System ; blood ; genetics ; Serologic Tests ; methods
6.Investigation of the characteristics of Rh blood group of Uygur nationality in Xinjiang.
Jiong-Cai LAN ; Hua-You ZHOU ; Xu-Hua BAI ; Xiao-Ping CHEN ; Yan-Zhao XING
Journal of Experimental Hematology 2007;15(4):885-887
		                        		
		                        			
		                        			The study was to investigate the characteristics of Rh blood group of Uygur nationality in Xinjiang. 1 230 blood samples of Uygur nationality were studied by Rh serological typing, modified antiglobulin test, chloroform/trichloroethylene absorption elution test, upstream, downstream and hybrid Rhesus boxes, 10 exons of D gene, RHD(psi) pseudogene. The results showed that the frequency of RHD negative was 5.8%, and no Del type was found. The further investigation of 72 samples of RhD (-) found that ccee (57.02%) and Ccee (29.08%) phenotype as well as RHD(-)/RHD(-) genotype (94.44%) and complete deletion type of D gene exon (91.12%) were all in high frequency, no RHD(psi) pseudugene was detected. In conclusion, the Rh blood group of Uygurs nationality in Xinjiang possesses both oriental and caucasian Rh characteristics, which enriches the diversity of blood types in chinesenation.
		                        		
		                        		
		                        		
		                        			Asian Continental Ancestry Group
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			China
		                        			;
		                        		
		                        			ethnology
		                        			;
		                        		
		                        			Gene Deletion
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Rh-Hr Blood-Group System
		                        			;
		                        		
		                        			genetics
		                        			
		                        		
		                        	
7.Screening analysis of irregular antibodies from random donor population in Shaoguan area.
Jian-Ying ZHU ; Jiong-Cai LAN ; Hong-Qing LUO
Journal of Experimental Hematology 2007;15(3):630-631
		                        		
		                        			
		                        			The study was purposed to analyze the frequency and distribution of irregular antibodies in Shaoguan area. Screening 15 033 random donor antibodies in Shaoguan area by screening cells, polybrene and antiglobulin tests. The results indicated that the irregular antibodies were found in 42 samples. The frequency of irregular antibodies in female was higher than that in male (P < 0.001), and Rh blood group antibodies such as anti-D, anti-E, and anti-Ec C were common (47.6%). 2 samples of Le antibodies were failed to be found by polybrene test. 2 samples of irregular antibodies with titer 2 were undiscovered by screening test of 10 pooled samples. In conclusion, because of irregular antibodies resulting in hemolytic transfusion reaction, the investigation of frequency and distribution of irregular antibodies is very important for safe transfusion. Antibody screening must be done for female donors, and especially for massive plasma transfusion of patients with severe and dangerous illness and infants so as to ensure safety.
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Blood Donors
		                        			;
		                        		
		                        			China
		                        			;
		                        		
		                        			Erythrocytes
		                        			;
		                        		
		                        			immunology
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Isoantibodies
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Mass Screening
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Rh-Hr Blood-Group System
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			immunology
		                        			;
		                        		
		                        			Rho(D) Immune Globulin
		                        			
		                        		
		                        	
8.A comparative research on RHD gene structures of Chinese Han and Uigur population.
Hua-you ZHOU ; Xu-hua BAI ; Yin-ze ZHANG ; Cong-rong WANG ; Qiong CAO ; Jiong-cai LAN
Chinese Journal of Medical Genetics 2006;23(2):151-155
OBJECTIVETo research comparatively on the RHD gene structures in unrelated RhD negative individuals of Chinese Uigur and Han population.
METHODSThe upstream, downstream, hybrid box and 10 exons of RHD gene were detected with sequence specific primer-PCR technique.
RESULTSThe results showed the genotypes of RhD negative individuals to have the significant difference between Chinese Uigur and Han population, that 94.44% Uigur individuals were with RHD(-)/RHD(-) genotype but just 61.40% Han population were with this genotype(94.44% versus 61.40%, P<0.01); 2.78% Uigur individuals were with RHD(+)/RHD(-) genotype but 34.21% Han population were with this genotype(2.78% versus 34.21%, P<0.01). However, there was significantly no RHD(+)/RHD(+) genotype difference between Chinese Uigur and Han population(2.78% versus 4.39%, P>0.05). In 78 cases of RhD negative Chinese Hans with single RHD gene, of which the RHD gene structure showed that 53(67.95%) cases were RHD(1-10) allele(of 53 RHD(1-10) alleles, 14 alleles were unexpressed); 15(19.23%) were RHD-CE(2-9)-D(2) allele; 5(6.41%) cases were RHD-CE(2-7)-D(2) allele; 2(2.56%) were similar to RHD-CE(3-6)D allele; 1(1.28%) case was RHD-CE(5-6)-D allele; and 2(2.56%) were RHD-CE(6)-D or point mutation respectively. Of 2 RhD negative Chinese Uigurs with RhD(-)/RHD(+) genotype, one carried RHD(1-10) allele, another carried RHD-CE(2-9)-D(2) allele.
CONCLUSIONThe most frequently unexpressed RHD alleles were RHD-CE(2-9)-D(2), RHD(1-10) and RHD-CE(2-7)-D(2) respectively in Chinese Han population who carried single RHD allele with RHD(-) phenotype and RHD(+) genotype. It showed the confluent character of RH gene in Chinese Han and Uigur population that there existed unexpressed RHD-CE(2-9)-D(2) allele in Chinese Uigur nationality, which was infrequent in Chinese Uigur population but frequent in Chinese Han population.
Alleles ; Asian Continental Ancestry Group ; genetics ; China ; ethnology ; Ethnic Groups ; ethnology ; genetics ; Exons ; genetics ; Genotype ; Humans ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Population Groups ; Rh-Hr Blood-Group System ; genetics
9.Comparison of Rhesus boxes in Hans and Uighurs.
Jiong-cai LAN ; Hua-you ZHOU ; Xu-hua BAI ; Gui-zhi PANG ; Xiao-zhu WANG ; Ling-jun CAI ; Qiong CAO ; Yin-ze ZHANG ; Rong XIA ; Quan-ke YANG
Chinese Journal of Medical Genetics 2005;22(5):580-582
OBJECTIVETo study the difference and similarity between Hans and Uighurs in regard to Rhesus box and its significance.
METHODSThe sequence specific primers of upstream, downstream and hybrid Rhesus boxes were designed on the basis of RHD gene sequence. The upstream, downstream and hybrid Rhesus boxes were determined by polymerase chain reaction-sequence specific primer(PCP-SSP) and mismatched PCR.
RESULTSThe percentage of RHD-/RHD-, RHD+/RHD- and RHD+/RHD+ genotypes ascertained in the unrelated Hans with RhD(-) were 61.40%, 34.21% and 4.39% respectively, while those in the unrelated Chinese Uighurs with RhD(-) were 94.44%, 2.78% and 2.78% respectively. Furthermore, all 6 cases of some other minorities were RHD-/RHD- types. The percentage of RHD-/RHD- and RHD+/RHD- genotypes ascertained in the unrelated Chinese Uighurs were significantly higher than those in Chinese Hans (P < 0.01), whereas no statistically significant difference in the percentage of RHD+/RDH+ genotype between the two groups was observed (P > 0.05).
CONCLUSIONThe Rh blood group of Uighurs in Xingjiang possesses both Oriental and Caucasian characteristics, which embodies a special ethnical aspect of the Chinese nation and is in accord with the anthropologic research results.
China ; Genetics, Population ; Genotype ; Humans ; Polymerase Chain Reaction ; Rh-Hr Blood-Group System ; genetics
10.Study on detection of samples of Rh-weak D and Del.
Xiao-Zhu WANG ; Jiong-Cai LAN ; Xu-Hua WU ; Hua-You ZHOU ; Wei-Jia LIU ; Dan LIU ; Cun-Sheng QI ; Feng-Qin ZENG ; Ke-Qing DU
Journal of Experimental Hematology 2005;13(3):509-511
		                        		
		                        			
		                        			To study the detection of weak D and Del from samples initially screened RhD(-), RhD phenotype was initially screened by routine serological test, out of which weak D phenotype was detected by indirect antiglobulin test (IAT) and Del phenotype was detected by chloroform-trichloroethylene absorption-elution test. The results showed that 56 samples were RhD(-) confirmed by routine serology test, which were screened out of 26 200 donors, among them 5 samples were typed as weak D by IAT and 9 cases samples were typed as Del by absorption-elution test. In conclusion, the samples which typed as RhD(-) by routine serological test must be identified by IAT and chloroform-trchloroethylene absorption test is order to detect weak D and Del phenotype. It is important for clinical transfusion safely.
		                        		
		                        		
		                        		
		                        			Blood Donors
		                        			;
		                        		
		                        			Blood Grouping and Crossmatching
		                        			;
		                        		
		                        			methods
		                        			;
		                        		
		                        			standards
		                        			;
		                        		
		                        			Epitopes
		                        			;
		                        		
		                        			immunology
		                        			;
		                        		
		                        			Erythrocytes
		                        			;
		                        		
		                        			immunology
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Rh-Hr Blood-Group System
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			immunology
		                        			
		                        		
		                        	
            
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