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BACKGROUND AND AIMS: Direct elimination of cccDNA remains a formidable obstacle due to the persistent and stable presence of cccDNA in hepatocyte nuclei. The silencing of cccDNA transcription enduringly is one of alternative strategies in the treatment of hepatitis B. Protein binding to cccDNA plays an important role in its transcriptional regulation; thus, the identification of key factors involved in this process is of great importance. APPROACHES AND RESULTS: In the present study, high mobility group nucleosome binding domain 1 (HMGN1) was screened out based on our biotin-avidin enrichment system. First, chromatin immunoprecipitation and fluorescent in situ hybridization assays confirmed the binding of HMGN1 with cccDNA in the nucleus. Second, functional experiments in HBV-infected cells showed that the promoting effect of HMGN1 on HBV transcription and replication depended on the functional region of the nucleosomal binding domain, while transfection of the HMGN1 mutant showed no influence on HBV compared with the vector. Third, further mechanistic exploration revealed that the silencing of HMGN1 increased the level of phosphorylase CLK2 and promoted H3 phosphorylation causing the reduced accessibility of cccDNA. Moreover, silenced HMGN1 was mimicked in HBV (r) cccDNA mouse model of HBV infection in vivo. The results showed that silencing HMGN1 inhibited HBV replication in vivo. CONCLUSIONS: In summary, our study identified that a host protein can bind to cccDNA and promote its transcription, providing a candidate strategy for anti-HBV targeting to interfere with the transcriptional activity of cccDNA microchromosomes.
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Proteína HMGN1 , Hepatite B , Animais , Camundongos , Histonas/metabolismo , Vírus da Hepatite B/fisiologia , Proteína HMGN1/genética , Proteína HMGN1/metabolismo , Cromatina , Proteínas de Transporte/genética , Fosforilação , Hibridização in Situ Fluorescente , Replicação Viral/genética , DNA Circular/genética , DNA Circular/metabolismo , Fatores de Transcrição/genética , Hepatite B/metabolismo , DNA Viral/genéticaRESUMO
OBJECTIVE@#To explore the clinical characteristics and genetic etiology for a child with atypical Hemolytic uremic syndrome (aHUS) in conjunct with nephrotic level proteinuria.@*METHODS@#A child patient who had visited the Affiliated Hospital of Qingdao University on June 25, 2020 was selected as the study subject. Clinical data of the patient was collected. Whole exome sequencing (WES) was carried out for the child, and candidate variant was verified by Sanger sequencing of the child and his parents.@*RESULTS@#The child, an 8-month-old male, had presented mainly with edema, oliguria, hematuria, nephrotic level proteinuria, anemia, thrombocytopenia, increased creatinine and urea, hypercholesterolemia but normal complement levels. Genetic testing revealed that he has harbored compound heterozygous variants of the DGKE gene, namely c.12_18dupGAGGCGG (p.P7fs*37) and c.1042G>T (p.D348Y), which were respectively inherited from his father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were classified as likely pathogenic and variant of uncertain significance, respectively. By combining his clinical manifestations and results of genetic testing, the child was diagnosed with aHUS with nephrotic level proteinuria.@*CONCLUSION@#For infants and young children with aHUS in conjunct with nephrotic level proteinuria, variants of the DGKE gene should be screened. Above finding has expanded the mutational spectrum of the DGKE gene.
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Lactente , Feminino , Humanos , Criança , Masculino , Pré-Escolar , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Mutação , Testes Genéticos , Trombocitopenia/genética , Proteinúria/genéticaRESUMO
Objective:To explore the application of collaborative nursing combined with medical integration model in minimally invasive surgery for pediatric urinary calculi, to provide clinical guidance for minimally invasive surgical nursing of urinary calculi in children.Methods:From December 2020 to July 2022, 90 children who underwent minimally invasive surgery for urinary calculi in Children′s Hospital Affiliated to Zhejiang University Medicine College were selected as subjects by quasi experiment. According to the time sequence of enrollment, they were divided into observation group ( n = 45) and control group ( n = 45). The control group was given routine nursing mode nursing, and the observation group was given collaborative nursing combined with medical integration mode nursing. The clinical related indicators, pain, anxiety and complications were compared between the two groups. Results:In the observation group, the operation time, the amount of bleeding during operation, the first time to get out of bed after operation, the rate of stone removal immediately after operation and the rate of stone removal 1 month after operation were (75.48 ± 5.92) min, (168.75 ± 17.28) ml, (6.12 ± 1.05) h, 84.44%(38/45) and 97.77%(44/45), respectively. The control group was (78.39 ± 6.75) min, (178.30 ± 19.25) ml, (6.84 ± 1.23) h, 64.44 % (29/45) and 82.22 %(37/45), respectively, the differences were statistically significant ( t/ χ2 = 2.17, 2.48, 2.99, 4.73, 6.05, all P<0.05). The Face, legges, Activity, Cry, Consolability Behavioral Tool scores of the observation group at 1 d, 3 d and 7 d after operation were 6.28 ± 1.21, 5.35 ± 1.37 and 2.87 ± 0.65, respectively, and those of the control group were 7.05 ± 1.55, 5.95 ± 1.25 and 3.21 ± 0.73, respectively, the differences were statistically significant ( t = 2.63, 2.17, 2.33, all P<0.05). The Modified Yale Preoperative Anxiety Scale and Frankl Compliance Scale Scores in the observation group at the day before discharge hospital were 55.28 ± 5.52, 3.60 ± 0.40, while in the control group were 60.02 ± 8.56, 2.82 ± 0.61, the differeces were significat ( t = 3.12, 3.02, both P<0.05). The incidence of complications was 2.22 %(1/45) in the observation group and 15.56 %(7/45) in the control group, the difference was significant ( χ2 = 4.94, P<0.05). Conclusions:The application of collaborative nursing combined with medical care integration model in minimally invasive surgery of urinary calculi in children has a significant effect.
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Based on 454 articles related to college students' entrepreneurial intention in the Web of Science Core Collection, this study explores the hotspots and trends of international research on college students' entrepreneurial intention by using a combination of coding and bibliometric analysis. The research hotspots are as follows: the theory of planned behavior is the main theoretical basis of these studies; entrepreneurship education is a more important predictor of college students' entrepreneurial intention, and this relationship is regulated by multiple variables; personal traits, several types of capital theories, social entrepreneurial intention, and quantitative research methods are also common. The research fronts include the following: systematic review of the field, continuous attention to the theory of planned behavior, and in-depth exploration of the differentiated influence of entrepreneurship education on entrepreneurial intention. Finally, we proposed research thinking and prospects related to research on undergraduates' entrepreneurial intention and entrepreneurship education.
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Objective:To evaluate and compare efficacy of intravenous immunoglobulin (IVIG) versus recombinant human tumor necrosis factor-α receptor Ⅱ:IgG Fc fusion protein (rhTNFR:Fc) in the treatment of toxic epidermal necrolysis (TEN) .Methods:Clinical data were collected from patients with TEN treated with IVIG or rhTNFR:Fc in Wuhan No.1 Hospital from 2013 to 2019. There were 11 patients in the IVIG group, including 3 males and 8 females, aged 25-72 years, and the median TEN-specific severity-of-illness score (SCORTEN) was 3 points; there were 10 patients in the rhTNFR:Fc group, including 5 males and 5 females, aged 32-84 years, and the median SCORTEN was 2 points. These patients all showed no response to the 5-day treatment with prednisolone acetate at a dose of 0.6-1.0 mg·kg -1·d -1, and then received IVIG at a dose of 400 mg·kg -1·d -1 for 5 consecutive days, or subcutaneous injection of rhTNFR:Fc at a dose of 25 mg every other day for 4-6 sessions. Changes in skin lesions and adverse events were recorded in the 2 groups. Statistical analysis was carried out by using Mann-Whitney U test. Results:Compared with the rhTNFR:Fc group, the IVIG group showed a significant decrease in the time to onset of reduction of skin lesion exudate (1.73 ± 1.19 days vs. 3.00 ± 1.56 days, P < 0.05) , time to onset of pain relief in the lesion area (1.64 ± 1.28 days vs. 3.70 ± 1.63 days, P < 0.05) , time to lightening of color of the lesion base (2.45 ± 1.12 days vs. 3.90 ± 1.59 days, P < 0.05) , time to onset of new epidermis growth (3.09 ± 1.13 days vs. 5.20 ± 1.22 days, P < 0.05) , and in the time to onset of lesion drying at the intertriginous sites (4.82 ± 2.22 days vs. 7.90 ± 3.14 days, P < 0.05) . However, there was no significant difference in the length of hospital stay between the IVIG group (17.70 ± 8.33 days) and rhTNFR:Fc group (16.70 ± 4.71 days, P > 0.05) . No adverse reactions were observed during the treatment, and no recurrence or complications were found in the 21 patients during the follow-up of 6 months. Conclusion:IVIG and rhTNFR:Fc are both effective in the treatment of TEN, but IVIG is superior to rhTNFR:Fc in terms of the time to onset of pain relief, skin lesion exudate reduction and epidermal growth.
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Objective@#The present study aimed to examine the mediated moderation effect underlying the association between parental psychological aggression and phubbing, as well as the mediating role of anxiety and moderating role of sex and grade. @*Methods@#Based on a cross-sectional study, a total of 758 Chinese junior high school students had completed measures on socio-demographic characteristics, parental psychological aggression, anxiety and phubbing. Structural equation modeling was adopted to examine the mediating effect of anxiety on the association between parental psychological aggression and phubbing. Multigroup analyses were conducted to explore whether the path coefficients differed by sex and grade. @*Results@#Mediation analysis indicated that anxiety could mediate the association between parental psychological aggression and phubbing. The indirect effect of parental psychological aggression on phubbing via anxiety was 0.12. Multigroup analyses revealed that the higher mediation effect of anxiety was more likely to be reported by boys and students from grade eight. @*Conclusion@#Findings of the present study may inform prevention and intervention programs for phubbing in adolescents exposed to parental psychological aggression, by decreasing the anxiety and adopting selective strategies for different sex and grade groups.
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Objective:To investigate the value of renal glucose threshold and related factors in patients with type 2 diabetes mellitus.Methods:According to the cut-off point of normal renal glucose threshold(RT G 8.9-10 mmol/L), 107 patients with type 2 diabetes mellitus hospitalized in the Endocrinology Department of our hospital were divided into three groups: high RT G group(RT G>10 mmol/L), medium RT G group(8.9 mmol/L≤RT G≤10 mmol/L), and low RT G group(RT G<8.9 mmol/L). The clinical data and biochemical characteristics of each group were collected and analyzed. Results:The proportions of patients with high, medium, and low RT G of type 2 diabetes mellitus were 56%, 29%, and 15%, respectively. There were significant differences in RT G value, age, course of disease, body mass index(BMI), fasting plasma glucose(FPG), HbA 1C, total cholesterol(TC), serum creatinine, mean blood glucose(MBG), and 24-hour urine glucose between high and medium RT G groups. RT G, gender, BMI, FPG, HbA 1C, TC, and MBG in patients with high RT G group were different from those in low RT G group. Only RT G revealed a difference between medium and low RT G groups. Correlation analysis showed that RT G was positively correlated with gender, age, BMI, HbA 1C, TC, and low density lipoprotein-cholesterol(LDL-C). Regression analysis showed that BMI, HbA 1C, and LDL-C were the related factors affecting the RT G of patients with type 2 diabetes. Conclusion:There is a larger proportion of patients with high RT G in type 2 diabetes mellitus. Their BMI, HbA 1C, and LDL-C are associated with RT G in the patients with type 2 diabetes mellitus.
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Objective:To summarize the clinical phenotype and genotype features of 2 children with adenosine deaminase 2 (ADA2) deficiency, and to review the related literature so as to enhance the understanding of this disease.Methods:The phenotype and genotype of 2 cases with ADA2 deficiency who visited the Affiliated Hospital of Qingdao University from March to December 2019 were analyzed.Literature was searched from foreign and domestic databases and studied to summarize clinical and gene mutation characteristics of children with ADA2 deficiency.Results:(1) ADA2 gene mutation was found in both children.One case was characterized by recurrent fever, livedo reticularis, polyarteritis nodosa and immunodeficiency.The mutation site c. 571delC(p.Q191Sfs*5)of the ADA2 gene detected in this case was a homozygous mutation, which was a new mutation point and not reported in China or abroad previously.The other case was characterized by recurrent fever, panniculitis, vasculitis with legs, and immunodeficiency.The mutation site c. 1358A>G(p.Y453C)was a homozygous mutation that was not reported in China previously.(2)There were 171 cases of children diagnosed with ADA2 deficiency in foreign countries, but only 5 cases (3 previously reported cases and 2 cases in this study) were detected in China.The main clinical phenotypes were recurrent fever(5/5 cases), livedo reticularis(4/5 cases), panniculitis(1/5 cases), cutaneous gangrene(1/5 cases), growth retardation(1/5 cases), cerebral infarction(3/5 cases), humoral immunodeficiency(4/5 cases), blood system involvement(3/5 cases), and myalgia(2/5 cases), elevated inflammatory markers(C-reactive protein, erythrocyte sedimentation rate)(5/5 cases). Conclusions:Children with ADA2 deficiency have various clinical phenotypes, and a good understanding of phenotypes can improve the level of clinical diagnosis and treatment.The mutation point of c. 571delC is a novel ADA2 gene mutation type, which further enriches the ADA2 gene spectrum.
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Rho GTPases have been shown previously to play important roles in several cellular processes by regulating the organization of the actin and microtubule cytoskeletons. However, the mechanisms of Rho GTPases that integrate the cellular responses during regeneration have not been thoroughly elucidated. The planarian flatworm, which contains a large number of adult somatic stem cells (neoblasts), is a unique model to study stem cell lineage development in vivo. Here, we focus on cdc42, which is an extensively characterized member among Rho GTPases. We found that cdc42 is required for the maintenance of epidermal lineage. Cdc42 RNAi induced a sustained increased of cell death and led to a loss of the mature epidermal cells but without affected cell division. Our results indicate that cdc42 function as an inhibitor to block the excessive apoptotic cell death in planarian epidermal regeneration and homeostasis.
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Apoptose/fisiologia , Epiderme/fisiologia , Proteínas de Helminto/metabolismo , Planárias/enzimologia , Regeneração/fisiologia , Proteína cdc42 de Ligação ao GTP/metabolismo , Animais , Proteínas de Helminto/genética , Planárias/genética , Proteína cdc42 de Ligação ao GTP/genéticaRESUMO
OBJECTIVE: This study aims to examine the parallel multiple mediators of depressive symptoms and sleep quality in the relations between stress and physical health-related quality of life (PHQOL)/mental health-related quality of life (MHQOL) among the women in late pregnancy. METHODS: Of 1120 pregnant women participated in the cross-sectional study which consisted of Perceived Stress Scale, Edinburgh Postnatal Depression Scale, Pittsburgh Sleep Quality Index and MOS 12-item Short Form Health Survey. Parallel multiple mediator models were used to analyze the relations between stress, depressive symptoms, sleep quality and PHQOL/MHQOL. RESULTS: The effect of perceived stress on PHQOL was partially through the indirect path of sleep quality (β=-0.061). But in the model for MHQOL, depressive symptoms and sleep quality played parallel mediators, and the indirect path effect of depressive symptoms (β=-0.179) was higher than sleep quality (β=-0.029). CONCLUSION: The findings contributed to the understanding about the influential mechanism of stress on PHQOL/MHQOL. And it reminded the importance of sleep quality and depressive symptoms for improving QOL in late pregnancy.
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Feminino , Humanos , Gravidez , Estudos Transversais , Depressão , Depressão Pós-Parto , Inquéritos Epidemiológicos , Negociação , Gestantes , Qualidade de VidaRESUMO
Objective To investigate the inhibitory effect of synthetic interferon‐induced transmembrane protein 1(IFITM1) siRNA on the proliferation and migration of human ovarian cancer cell line CP 70 .Methods The siRNA targeted IFITM1 was transfected into CP70 cells by LipofectamineTM 2000 . Expressions of IFITM1 mRNA and protein were examined by qRT‐PCR and Western blot .Plate clone assay and Transwell chamber were used to observe the proliferation and migration of CP 70 cells .Results IFITM1 siRNA significantly inhibited the expression of IFITM1 in human ovarian cancer cell line CP70 at both mRNA and protein levels . The colony formation assay indicated that the clone number was 84 in IFITM1siRNA , which was much fewer than 181 in negative control group and 178 in mock transfection group .The colony‐forming efficiency (CFE) was 42% ,90 .5%and 89% ,respectively .Transwell chamber results showed that the number of migrated cells was 59 ,121 and 126 , respectively ;the siRNA transfection group differed significantly from the other two groups , indicating that downregulated IFITM1 expression greatly inhibited the proliferation and migration of CP 70 cells .Conclusion Knockdown of IFITM1 inhibited the proliferation and migration of CP70 cells .IFITM1 is a potential therapeutic target for human ovarian cancer .
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Objective To understand the status quo of ICU nurses career situations and its influencing factors in Shandong province. Methods A total of 247 ICU nurses were investigated by questionnaires on career condition. Results The career condition score was 79.19 ± 11.63. In addition, statistical significances were revealed by occupational career questionnaire of ICU nurses in different aspect of the scores with age, gender, working years in the ICU, access years to ICU nurses specialist, whether to participate in career training. The scores of career condition and career identity ICU nurses were different, the 40-years-older group was higher than 31-40 years group (P=0.007, P=0.005). The dimension scores of male nurses organizational commitment was higher than that of female nurses(P=0.002). The scores of career condition whose ICU working life more than 16 years were higher than those of within 5 years(P=0.013). The career condition scores of the ICU nurses with access years of specialist qualifications 7-9 years was higher than those of within 3 years(P=0.011). Conclusions The career condition score of ICU clinical nurse specialists was at a medium level, it still needs to be further improved, managers should pay attention to the different levels of nurses to provide career training, in order to promote the professional development of critical care nurses.
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Background High myopia is seriously harmful to visual function.To explore the mechanism of high myopia is significant for the prevention and treatment.Complement proteins C1q and C3 have emerged as critical mediators of synaptic refinement and plasticity,however,their effects in retina on myopia remain elusive.Objective This study was to investigate the expressions of complement factors C1q and C3 in the retina with negative lensdefocused myopia in guinea pigs.Methods The use and care of animals complied with the application of Peking Union Medical College Hospital Iaboratory Animal Welfare Ethics Committee.Twelve 3-day-old pigmented guinea pigs were assigned randomly to the lens-defocused group and the normal control group.The left eyes were covered by -10 D PMMA lens for 4 weeks as the defocused eye group,and the right eyes were covered using 0 D PMMA lens in the same way as the fellow control eye group.The right eyes of the normal guinea pigs were used as the normal control eye group.The refractive diopter of guinea pigs was examined by retinoscopy.The animals were sacrificed at the fourth week and the expressions of complement C1q and C3 in the retinas of guinea pigs were detected by Western blot.Results The diptors were (-1.21±0.71)D,(+2.46±0.75)D and (+1.75±0.50)Din the defocused eye group,normal eye group and the fellow eye group at the fourth week,showing a significant difference among the groups (F=51.55,P=0.69),and diopters were insignificantly different between the normal eye group and fellow eye group (q =2.62,P=0.08).However,the diopters of the defocused eye group were significantly higher than those of the fellow eye group (q =10.92,P<0.01).The expressions of C1q and C3 proteins in the retinas were significantly different among the defocused eye group,fellow eye group and normal eye group (C1 q:F=8.810,P =0.003;C3:F =14.490,P<0.001),and expression levels of C1q and C3 proteins in the defocused eye group were significant higher than those of the fellow eye group (C1q:q=4.14,P=0.01 ;C3:q=4.71,P=0.005) ;while no significant differences were found between the fellow eye group and the normal eye group (C1q:q =1.61,P =0.27; C3:q =2.82,P =0.070).Conclusions The expression levels of C1q and C3 up-regulate in the retinas with lens-defocused myopic animal model.Excessive complement activation in retinas may be involved in the development of myopia.
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Objective To discuss the maternal and neonatal outcomes in gestational diabetes patients given insulin therapy at different periods.Methods Clinical data of 52 cases of gestational diabetes patients admitted from May 2011 to June 2013 in The Central Hospital of Ningbo Development Zone were analyzed,among whom 28 cases accepted insulin therapy before 32 weeks of pregnancy(early diagnosis treatment group)and the rest 24 cases accepted insulin therapy after 32 weeks of pregnancy(late diagnosis treatment group).The pregnancy outcome,hemodynamic parameters,incidence of hypertension,and the outcome of neonates were compared.Results The blood glucose of the 52 patients was controlled in the normal range after insulin therapy.However,incidence of preterm and cesarean section was significantly higher in the early diagnosis treatment group than that in the late diagnosis treatment group (P < 0.05).The incidence of neonatal ketosis,fetal distress,and the incidence of macrosomia was significantly lower in the early treatment group than that in late diagnosis treatment group (P < 0.05).The incidence of pregnancy-induced hypertension had not statistical difference between the two groups of pregnant women(P > 0.05).S/D value of the two groups of pregnant women had no statistical significance(P > 0.05).RI and PI value was significantly higher in the late diagnosis treatment group than those in early diagnosis treatment group(P <0.05).Conclusions The blood glucose of patients was controlled in the normal range after insulin therapy.Insulin therapy before 32 weeks of pregnancy can improve pregnancy outcomes.However,further research is needed for specific treatment programs.
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Effects of light quality and germplasm on the growth and effective ingredients of Dendrobium officinale germchit were studied. Under 8 light qualities (red, blue, yellow, green and three different red blue mix light), test-tube plantlets of different families (9 x 66, 17 x 30, 78 x 68) were used in the experiment to measure economical character and determine the content of chlorophyll, polysaccharides and total alkaloids. The results showed that light quality, germplasm and their interaction had a significant effect on the growth of D. officinale germchit. The maximal root length and height of seedling were obtained under red light, under blue light, the stem diameter was thickest and the content of total alkaloids were highest, the content of chlorophyll and polysaccharides of test-tube plantlets under red blue mix light were higher than that of other treatments. This work has laid a foundation for the high quality, low carbon and efficient production of D. officinale, and gives useful tips on production of high quality ingredients.
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Alcaloides , Metabolismo , Cruzamento , Clorofila , Metabolismo , Dendrobium , Genética , Efeitos da Radiação , Luz , Raízes de Plantas , Genética , Efeitos da Radiação , Caules de Planta , Genética , Efeitos da Radiação , Polissacarídeos , Metabolismo , Plântula , Genética , Efeitos da RadiaçãoRESUMO
Objective To investigate the association of two single nucleotide polymorphisms (SNPs),rs844648 and rs3850641,in OX40L (TNFSF4) gene,with systemic lupus erythematosus(SLE) in Hubei Han populations.Methods A total of 82 patients with SLE and 100 normal human controls were eligible for this study.Blood samples were obtained from these subjects and DNA was extracted from these samples.PCR-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the genotype of SNPs rs844648 and rs3850641.Results The frequency of AA,AG and GG genotype of the SNP rs844648 was 14.0%,55.0%and 31.0% respectively in the controls,20.7%,62.2% and 17.1% respectively in the patients.A higher frequency was observed for A allele at the SNP rs844648 and G allele at the SNP rs3850641 in patients compared with the normal controls [73.2% vs.69.0%%,x2 =4.69,P < 0.05,OR =2.182 (1.068 - 4.458);37.8% vs.24.0%,x2 =4.07,P < 0.05,OR =1.925 (1.015 - 3.651)].The frequency of AA,AG and GG genotype of SNP rs3850641 was 76.0%,21.0% and 3.0% respectively in the normal controls,62.2%,31.7% and 6.1% respectively in the patients.Conclusions There are polymorphisms in the SNPs rs844648 and rs3850641 in TNFSF4 gene,which may be associated with the development of SLE.