1.Genotype Analysis of Common and Rare Thalassemia in People of Reproductive Age in Huadu District,Guangzhou
Ai-Ping JU ; Xiao-Tong FU ; Keng LIN ; Bi-Qiu XU ; Jian-Zhen LIU ; Yan-Ling QIN ; Xi-Chong LI
Journal of Experimental Hematology 2024;32(5):1496-1502
		                        		
		                        			
		                        			Objective:To analyze the genotypes distribution of common and rare thalassemia in people of reproductive age in Huadu district of Guangzhou,enhance the database of thalassemia.Methods:Peripheral blood samples were collected for genotype analysis in Maternity and Child Health Hospital of Huadu District from January 2016 to October 2022.Gap-PCR and Reverse dot blot hybridization were used to detect common thalassemia genotypes.DNA sequencing was performed in samples suspected of rare genotypes.Results:A total of 16 171 subjects were identified as thalassemia carriers,and the positive rate was 44.41%(16 171/36 412).The genotypes of 114 cases(0.31%)were rare.A total of 10 845 cases were identified as α-thalassemia carriers(29.78%),and--SEA/αα was the most common genotype in those people,followed by-α3.7/αα and-α4.2/αα.A total of 4 531 subjects were identified as common β-thalassemia carriers(12.44%).The most common β-thalassemia mutation in the population was β41-42/βN,followed by β654/βN and β-28/β N.A total of 681 subjects were identified as αβ thalassemia carriers(1.87%),among them--SEA/αα compounded withβ CD41-42/β N was the most common genotype.A total of 48 cases were identified as rare α-thalassemia carriers,14 types of mutations,in which Fusion gene/αα was the most common.A total of 52 cases were identified as rare β-thalassemia carriers,11 types of mutation,in which βSEA-HPFH/βN was the most common.Conclusion:The thalassemia genotypes in Huadu district are complex and diverse.We should attach great importance to the detection of rare thalassemia genotypes.
		                        		
		                        		
		                        		
		                        	
2.Evaluation of the residual risk of HIV transmission through blood transfusion after nucleic acid testing in blood centers in China
Yanhong WAN ; Zhijun ZHEN ; Ying LI ; Yanqin HE ; Feng YAN ; Dongmin ZHANG ; Shouguang XU ; Nan WU ; Kejin LI ; Youhua SHEN ; Lin BAO ; Xiaoli CAO ; Xia DU ; Jianling ZHONG ; Weiping FENG ; Peng WANG ; Ying LI ; Dong GUO ; Yang LIU ; Li LI ; Xinyan FAN ; Junbing ZHOU ; Xiaotong SUN ; Lijun ZHOU ; Liping NENG ; Bing JU ; Fang WANG ; Yan QIU
Chinese Journal of Experimental and Clinical Virology 2023;37(4):361-366
		                        		
		                        			
		                        			Objective:To evaluate the residual risk (RR) of transfusion transmitted HIV (TT-HIV) after the implementation of nucleic acid amplification test (NAT) in blood screening test among blood centers in China.Methods:The data of blood donors and HIV infection markers from 2017 to 2020 were collected from 28 blood centers via the Platform of Comparison of blood establishments Practice in Chinese Mainland. The new infection rate/window period mathematical model was used for two types of blood screening strategies, namely, two rounds ELISA plus individual NAT take turn with pooling NAT (2ELISA+ ID-NAT/MP-NAT) and two ELISA plus one round pooling NAT (2ELISA+ MP-NAT), and the RR of HIV infection was estimated also based on first donors (FDs) and repeated donors (RDs) in different blood donation years. T-test analyses were conducted for comparing TT HIV RR among FDs and RDs in different blood donation years with two blood screening strategies, and the variation trend of RR in HIV test was observed.Results:From 2017 to 2020, the RR of FDs in 2ELISA+ ID-NAT/MP-NAT blood screening strategy was 2.869/10 6 person-year, 3.795/10 6 persons-year, 3.879/10 6 person-year, and 2.890/10 6 person-year respectively. The RR of RDs was 1.797/10 6 person-year, 1.502/10 6 person-year, 1.857/10 6 person-year, and 1.483/10 6 person-year respectively. Significant difference exists between RR of FDs and RDs, with F=9.898 and p<0.05. In 2ELISA+ MP-NAT strategy, the RR of FDs was 3.508/10 6 person-year, 1.868/10 6 person-year, 2.204/10 6 person-year, and 1.765/10 6 person-year respectively. The RR of RDs was 0.948/10 6 person-year, 0.926/10 6 person-year, 0.748/10 6 person-year, and 0.682/10 6 person-year respectively. Statistical difference existed between RR of FDs and RDs, with F=17.126 and P<0.05. There was no significant difference between the RR of FDs in these two strategies with F=3.493 and P>0.05, while there was a difference between the RR of RDs in these two strategies with F=24.516 and P<0.05, and a difference between the RR of total donors (TDs) in these two strategies F=20.216 and P<0.05. Conclusions:The RR of TT HIV significantly decreased after the introduction of NAT into blood test among blood centers in China. There were some differences in the RR of HIV testing among different blood screening strategies. There could be significant differences in the RR of HIV testing among different groups of blood donors. Compared with FDs, RDs is the low risk group for HIV.
		                        		
		                        		
		                        		
		                        	
3.Causes analysis of blood donor deferral in 20 domestic blood centers
Dongyan ZHAO ; Bing JU ; Hai QI ; Heng ZHANG ; Lixian MA ; Rong GUO ; Ling HOU ; Lin BAI ; Yang ZHANG ; Tao QI ; Yang CHEN ; Wenjie HU ; Xiaojun XU ; Rui CHEN ; Lin WANG ; Tao LI ; Wei LUO ; Ning CHENG ; Honghua LIU ; Junying LI ; Yan QIU
Chinese Journal of Blood Transfusion 2022;35(4):360-364
		                        		
		                        			
		                        			【Objective】 To investigate the main causes of blood donor deferral in domestic blood center. 【Methods】 The causes of donor deferral were classified into 12 categories as previous medical history, drug use, alcohol consumption, menstrual period, underweight, abnormal blood pressure, abnormal body temperature, abnormal hemoglobin (Hb), lipemic blood, positive hepatitis B surface antigen (HBsAg), elevated alanine aminotransferase (ALT) and others according to the comparison indicators of Asia-Pacific Blood Network (APBN) and the national standard Blood Donor Health Examination Requirements. The relevant data of the top 3 causes of donor deferral, voluntarily reported by the members of Practice Comparison Working Group of China’s Mainland Blood Collection and Supply Institutions from 2014 to 2019, were collected and a histogram was generated. 【Results】 The median donor deferral rate of 20 domestic blood centers from 2014 to 2019 was 12.14%, with the lowest at 0.18% and highest at 32.32%, respectively. The top three causes for donor deferral were elevated ALT, abnormal Hb and abnormal blood pressure in year 2014, 2015, 2018 and 2019; elevated ALT, lipemic blood and abnormal blood pressure in 2016; elevated ALT, abnormal Hb, and lipemic blood in 2017. 【Conclusion】 The main causes of donor deferral were elevated ALT, abnormal Hb, abnormal blood pressure and lipemic blood.
		                        		
		                        		
		                        		
		                        	
4.Incidence of extrauterine growth retardation and its risk factors in very preterm infants during hospitalization: a multicenter prospective study.
Wei SHEN ; Zhi ZHENG ; Xin-Zhu LIN ; Fan WU ; Qian-Xin TIAN ; Qi-Liang CUI ; Yuan YUAN ; Ling REN ; Jian MAO ; Bi-Zhen SHI ; Yu-Mei WANG ; Ling LIU ; Jing-Hui ZHANG ; Yan-Mei CHANG ; Xiao-Mei TONG ; Yan ZHU ; Rong ZHANG ; Xiu-Zhen YE ; Jing-Jing ZOU ; Huai-Yu LI ; Bao-Yin ZHAO ; Yin-Ping QIU ; Shu-Hua LIU ; Li MA ; Ying XU ; Rui CHENG ; Wen-Li ZHOU ; Hui WU ; Zhi-Yong LIU ; Dong-Mei CHEN ; Jin-Zhi GAO ; Jing LIU ; Ling CHEN ; Cong LI ; Chun-Yan YANG ; Ping XU ; Ya-Yu ZHANG ; Si-Le HU ; Hua MEI ; Zu-Ming YANG ; Zong-Tai FENG ; San-Nan WANG ; Er-Yan MENG ; Li-Hong SHANG ; Fa-Lin XU ; Shao-Ping OU ; Rong JU
Chinese Journal of Contemporary Pediatrics 2022;24(2):132-140
		                        		
		                        			OBJECTIVES:
		                        			To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China.
		                        		
		                        			METHODS:
		                        			A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined.
		                        		
		                        			RESULTS:
		                        			The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05).
		                        		
		                        			CONCLUSIONS
		                        			It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
		                        		
		                        		
		                        		
		                        			Female
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		                        			Fetal Growth Retardation
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		                        			Gestational Age
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		                        			Hospitalization
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		                        			Humans
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		                        			Incidence
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		                        			Infant
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		                        			Infant, Newborn
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		                        			Infant, Premature
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		                        			Infant, Very Low Birth Weight
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		                        			Prospective Studies
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		                        			Risk Factors
		                        			
		                        		
		                        	
5.Application and clinical efficacy of ultrasound debridement method in residual burn wounds.
Ze Liang HE ; Jin LI ; Zhen Yang SUI ; Ju Lei ZHANG ; Liang En AN ; Ling Ling LIU ; Cheng Liang ZHANG ; Yuan Yuan YAO ; Shu Lin QIU ; Xiao Dong LI
Chinese Journal of Burns 2022;38(11):1034-1039
		                        		
		                        			
		                        			Objective: To investigate the application and clinical efficacy of ultrasound debridement method in residual burn wounds. Methods: A retrospective cohort study was conducted. From August 2017 to August 2021, 64 patients with residual burn wounds who met the inclusion criteria were admitted to the 980th Hospital of the Joint Logistic Support Force of PLA. According to the debridement method adopted for the residual wounds, the patients were divided into ultrasound debridement group (34 cases, 22 males and 12 females, aged (31±13) years) and traditional debridement group (30 cases, 19 males and 11 females, aged (32±13) years). After the corresponding debridement, the wounds of patients in the two groups were selected for stamp skin grafting or large skin grafting according to the wound site and skin donor status. For unhealed wounds after stage Ⅰ surgery, secondary debridement and skin grafting were be performed, with the wound debridement methods in the 2 groups being the same as those of stage Ⅰ, respectively. On postoperative day 3, drug-sensitive test was used to detect the bacteria in the wound and the positive rate of bacteria was calculate. On postoperative day 7, the survival rate of skin slices in wound and the incidence of subcutaneous hematoma were calculated. At discharge, wound healing time and debridement times of patients were counted, and the secondary debridement rate was calculated. Data were statistically analyzed with independent sample t test or chi-square test. Results: On postoperative day 3, the wounds in ultrasound debridement group were infected with Staphylococcus aureus in 2 cases and Pseudomonas aeruginosa in 2 cases, and the wounds in traditional debridement group were infected with Staphylococcus aureus in 5 cases, Pseudomonas aeruginosa in 3 cases, Acinetobacter baumannii in 1 cases, Klebsiella pneumoniae in 1 cases, and Enterobacter cloacae in 1 cases. The positive rate of bacteria of wound in ultrasound debridement group was significantly lower than that in traditional debridement group (χ2=5.51, P<0.05). On postoperative day 7, the survival rate of skin grafts in ultrasound debridement group was (92±5) %, which was significantly higher than (84±10) % in traditional debridement group (χ2=6.78, P<0.01); the incidence of subcutaneous hematoma in ultrasound debridement group was 17.6% (6/34), which was significantly lower than 40.0%( 12/30) in traditional debridement group, χ2=3.94, P<0.05. At discharge, the wound healing time in ultrasound debridement group was (11.0±2.0) d, which was significantly shorter than (13.0±3.1) d in traditional debridement group (t=3.81, P<0.01); the secondary debridement rate of wounds in ultrasound debridement group was 2.9% (1/34), which was significantly lower than 20.0% (6/30) in traditional debridement group (χ2=4.76, P<0.05). Conclusions: Ultrasound debridement method can significantly reduce the bacterial load of residual burn wounds, reduce postoperative hematoma formation, and promote the survival of skin grafts to shorten the course of disease of patients.
		                        		
		                        		
		                        		
		                        			Male
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		                        			Female
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		                        			Humans
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		                        			Debridement/methods*
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		                        			Retrospective Studies
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		                        			Treatment Outcome
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		                        			Bacteria
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		                        			Burns/microbiology*
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		                        			Hematoma
		                        			
		                        		
		                        	
6.Risk factors of bronchopulmonary dysplasia in very preterm infants: a national multicenter study
Ruihua BA ; Lixia TANG ; Wei SHEN ; Lian WANG ; Zhi ZHENG ; Xinzhu LIN ; Fan WU ; Qianxin TIAN ; Qiliang CUI ; Yuan YUAN ; Ling REN ; Jian MAO ; Yumei WANG ; Bizhen SHI ; Ling LIU ; Jinghui ZHANG ; Yanmei CHANG ; Xiaomei TONG ; Yan ZHU ; Rong ZHANG ; Xiuzhen YE ; Jingjing ZOU ; Huaiyu LI ; Baoyin ZHAO ; Yinping QIU ; Shuhua LIU ; Li MA ; Ying XU ; Rui CHENG ; Wenli ZHOU ; Hui WU ; Zhiyong LIU ; Dongmei CHEN ; Jinzhi GAO ; Jing LIU ; Ling CHEN ; Cong LI ; Chunyan YANG ; Ping XU ; Yayu ZHANG ; Sile HU ; Hua MEI ; Zuming YANG ; Zongtai FENG ; Sannan WANG ; Eryan MENG ; Lihong SHANG ; Falin XU ; Shaoping OU ; Rong JU
Chinese Pediatric Emergency Medicine 2022;29(6):433-439
		                        		
		                        			
		                        			Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.
		                        		
		                        		
		                        		
		                        	
7.Evaluation and study on the effect of nucleic acid testing in blood screening on the residual risk of transfusion transmitted HBV infection
Min HUANG ; Lin BAI ; Changchun LU ; Shanshan ZHU ; Yujun LI ; Zhian ZHANG ; Haili MA ; Rong YOU ; Yanli QIN ; Bing JU ; Wei HAN ; Fang WANG ; Xue CHEN ; Xiaohua YUAN ; Xingli REN ; Lei ZHAO ; Linghao ZHANG ; Xing YI ; Yan QIU
Chinese Journal of Experimental and Clinical Virology 2022;36(4):429-435
		                        		
		                        			
		                        			Objective:To preliminarily estimate and study the effect of nucleic acid testing in blood screening on the residual risk (RR) of transfusion transmitted HBV infection (TTI HBV).Methods:Using the NAT yield/WP ratio model and adopting the relevant data of information management system of practice comparison working party in the Mainland of China, this paper analyzed the trend of the RR of TTI HBV among 18 blood centers from 2015 to 2019 in China, and compared the impact of two kinds of blood screening strategies which were ELISA+ ID-NAT/MP-NAT (individual-donation nucleic acid testing or mini-pool nucleic acid testing) and ELISA + MP-NAT on RR in 2019.Results:The overall trends of the 5-year RR of HBV among 18 blood centers showed by trend chi square test were NAT single positive rate trend χ2= 39.42( P<0.01) and residual risk trend χ2= 279.792( P<0.01); The influence on RR from the differences of ELISA+ ID-NAT/MP-NAT and ELISA+ MP-NAT was statistically significant, and chi square test showed that χ2= 7.4( P<0.01). Conclusions:Since the implementation of nucleic acid testing in the blood screening in China from 2015, the residual risk of transfusion transmitted HBV infection has decreased year by year. The observed two blood screening strategies which dominated in China may lead to discrepancy in the residual risk of TTI.
		                        		
		                        		
		                        		
		                        	
8.Association between sleep quality and risk of acute exacerbation of mild and moderate chronic obstructive pulmonary disease: a community-based prospective study
Tao LIN ; Qian XU ; Kang WU ; Hua QIU ; Ying-ying WANG ; Xiao-lin LIU ; Xiao-nan WANG ; Ju-zhong KE ; Zhi-tao LI ; Xiao-dan CHEN ; Qing-ping LIU ; Chao-wei FU ; Xiao-nan RUAN ; Na WANG
Shanghai Journal of Preventive Medicine 2021;33(11):989-994
		                        		
		                        			
		                        			Objective:To investigate the association between sleep quality and the risk of acute exacerbation in mild and moderate chronic obstructive pulmonary disease (COPD) patients in Pudong New Area of Shanghai. Methods:This was a prospective study involving eligible mild and moderate COPD patients from 10 communities randomly selected in Pudong New District of Shanghai. A structured questionnaire was used to collect demographic characteristics, clinical information and information on acute exacerbation. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) in Chinese. Multiple negative binomial regression was used to estimate the association between sleep quality and risk of exacerbation. Results:Altogether 212 mild/moderate COPD patients participated and completed the entire survey, of whom the majority (95.8%) were mild COPD patients, 110 persons female and over half (54.2%) over 65 years old. 32.9% of the patients had poorer sleep quality at baseline. 18.9% of the patients reported exacerbation over the past year during follow-ups. Multiple negative binomial regression suggested that increased PSQI was related to higher risk of exacerbation (
		                        		
		                        	
9.Association between serum trace elements and dyslipidemia: a community-based cross-sectional study
Ju-zhong KE ; Yan HU ; Tao LIN ; Xiao-lin LIU ; Kang WU ; Hua QIU ; Xiao-nan WANG ; Zhi-tao LI ; Ming ZHAN ; Xiao-nan RUAN
Shanghai Journal of Preventive Medicine 2021;33(11):1070-1075
		                        		
		                        			
		                        			Objective:To investigate the association between serum trace elements and dyslipidemia in Pudong New Area. Methods:A community-based cross-sectional study was carried out. A stratified, cluster sampling approach was used for sampling. In total 1 814 community residents aged above 35 years old were recruited in Pudong New Area, Shanghai. A face-to-face investigation was conducted and blood samples were collected. Serum levels of 16 trace elements, including boron, vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc, arsenic, selenium, strontium, molybdenum, tin, antimony, and barium were measured by inductively coupled plasma mass spectrometry (ICP-MS). The relationship between serum trace elements and dyslipidemia was analyzed with single and multiple Logistic regression models. Results:Prevalence of dyslipidemia is higher among participants of more than 45 years old with high BMI, hypertension or diabetes.Serum iron leveled the highest, followed by copper, zinc, selenium, strontium, boron and other trace elements. After adjusting for potential confounders, the odds ratios of dyslipidemia associated with the highest quartile of trace elements concentrations were 1.41 (95%
		                        		
		                        	
10.Analysis of Gene Mutation Types of Thalassemia in Fuzhou Area of China.
Peng-Ju CAO ; Liang-Yuan CHEN ; Li-Li JIANG ; Yang YANG ; Shao-Ting CHEN ; Chun-Li HUANG ; Qiu-Qin ZHANG ; Qiu-Mei WU ; Fa-Lin CHEN
Journal of Experimental Hematology 2019;27(3):893-898
		                        		
		                        			OBJECTIVE:
		                        			To investigate the gene mutation types and spectrum of α, β-thalassemia in Fuzhou area of China.
		                        		
		                        			METHODS:
		                        			Thalassemia gene screening was performed in the women receiving physical, prenatal, and pre-pregnancy examination, and the patients with suspected thalassemia in our hospital from July 2013 to March 2018.Genotypes of thalassem were detected by Gap-PCR and RDB-PCR.
		                        		
		                        			RESULTS:
		                        			1042 were positive among 2074 suspected cases with a positive rate of 50.24%; 618 cases were confirmed to be α-thalassemia and with a positive rate of 29.8%; 409 cases were confirmed to be β-thalassemia with a positive rate of 19.72%. 15 cases were confirmed to be α-β complex thalassemia with a positive rate of 0.72%. the --/αα(76.54%) was the most common genotype among α-thalassemia, -α/αα(10.03%) and -α/αα(2.91%) in hot pursuit. In addition, IVS-II-55 (T->G) and IVS-II-119 (-G, +CTCGGCCC) were newly found alpha mutations; the IVS-2-654 (C→T) (40.83%) was the most common genotype among β-thalassemia, CD41-42 (-TCTT) (35.94%) and CD17 (A→T) (9.78%) in hot pursuit.
		                        		
		                        			CONCLUSION
		                        			The genotype of thalassemia in Fuzhou area is highly heterogenic, --/αα is the most common genotype among α-thalassemia, IVS-2-654 (C→T) is the most common genotype among β-thalassemia, Meanwhile, two α-mutation sites are found in this study which were not reported in the Database of Human Hemoglobin Variants and Thalassemias.
		                        		
		                        		
		                        		
		                        			China
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		                        			Female
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		                        			Genotype
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		                        			Humans
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		                        			Mutation
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		                        			Pregnancy
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		                        			alpha-Thalassemia
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		                        			beta-Thalassemia
		                        			
		                        		
		                        	
            
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