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Objective:To investigate the effect of rumination on learning burnout of nursing undergraduate students and the mediating role of psychological capital between rumination and learning burnout of nursing undergraduate students.Methods:A total of 296 undergraduate nursing students from three medical colleges were assessed by using ruminative responses scale, learning burnout questionnaire and psychological capital scale. SPSS 20.0 was used for t-test. Pearson correlation was to analyze the relationship among psychological capital, learning burnout and ruminative thinking. AMOS 20.0 was used to construct and analyze the mediating model of psychological capital and its mediating effect was tested by Bootstrap method. Results:The average score of rumination of nursing undergraduate students was 46.60±11.40, learning burnout score was 56.18±11.25, and psychological capital scale score was 99.93±15.27. There was a significant difference among the rumination, psychological capital, and learning burnout scores in whether there was curriculum failure ( P < 0.05). The total score of rumination was positively related to the total score of learning burnout ( r = 0.39, P < 0.01), and was negatively related to the total score of psychological capital ( r = -0.53, P < 0.01). The total score of rumination was negatively related to the total score of psychological capital ( r = -0.46, P < 0.01). The psychological capital played a partial mediating role between rumination and learning burnout. The mediating effect value was 0.216, accounting for 61.521% of the total variation. Conclusion:The rumination can both directly affect the learning burnout of nursing undergraduate students and indirectly affect the learning burnout through psychological capital. Psychological capital plays a bridge role in improving rumination related to learning burnout.
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Measuring eye movement is a fundamental approach in cognitive science as it provides a variety of insightful parameters that reflect brain states such as visual attention and emotions. Combining eye-tracking with multimodal neural recordings or manipulation techniques is beneficial for understanding the neural substrates of cognitive function. Many commercially-available and custom-built systems have been widely applied to awake, head-fixed small animals. However, the existing eye-tracking systems used in freely-moving animals are still limited in terms of their compatibility with other devices and of the algorithm used to detect eye movements. Here, we report a novel system that integrates a general-purpose, easily compatible eye-tracking hardware with a robust eye feature-detection algorithm. With ultra-light hardware and a detachable design, the system allows for more implants to be added to the animal's exposed head and has a precise synchronization module to coordinate with other neural implants. Moreover, we systematically compared the performance of existing commonly-used pupil-detection approaches, and demonstrated that the proposed adaptive pupil feature-detection algorithm allows the analysis of more complex and dynamic eye-tracking data in free-moving animals. Synchronized eye-tracking and electroencephalogram recordings, as well as algorithm validation under five noise conditions, suggested that our system is flexibly adaptable and can be combined with a wide range of neural manipulation and recording technologies.
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Objective:To evaluate the effect of canagliflozin on intrarenal fat content and oxygenation in newly-diagnosed type 2 diabetes patients.Methods:Twenty-three newly-diagnosed type 2 diabetes patients were divided into canagliflozin( n=11) and glimepiride control( n=12) groups .Both groups received MRI scanning with Dixon MRI and BOLD MRI sequence to assess patients′ intrarenal fat content, oxygenation level before treatment and 24 weeks after treatment. Fasting blood glucose, glycosylated hemoglobin, blood uric acid, blood lipids, blood pressure, weight, and other metabolic index were also tested before and after treatment. Furthermore, the relationship between body mass index(BMI) and intrarenal fat content and the correlation between changes in intrarenal fat content and improvement in renal hypoxia were analyzed. Results:No significant differences were found in baseline age, body weight, fasting blood glucose, glycosylated hemoglobin, blood lipid, and serum uric acid between the two groups. There was no significant difference in fasting blood glucose, glycosylated hemoglobin, cholesterol(CHO), low-density lipoprotein-cholesterol(LDL-C), and triglycerides(TG) levels in both groups after 12 and 24 weeks of treatment. The decrease in body weight, blood uric acid level, and diastolic blood pressure from baseline in the canagliflozin group was greater than those in the control group( P<0.05). Two groups of patients with type 2 diabetes at baseline had no obvious difference in intrarenal fat content, and the patients′ BMI showed no obvious correlation with degree of intrarenal fat accumulation. Canagliflozin treatment for 24 weeks could reduce intrarenal fat content, which was higher than that of control group. The R2 * values of renal cortex and medulla in the canagliflozin group decreased from baseline by 19.22% and 22.63% respectively( P<0.05), whereas no significant difference was seen in the glimepiride control group. The decrease of intrarenal fat content in the canagliflozin group was related to the improvement of renal cortex and medulla oxygenation. Conclusion:Canagliflozin can reduce intrarenal fat accumulation and improve renal cortical hypoxia in newly diagnosed type 2 diabetes patients with normal renal function.
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Objective:Since December 2019, novel coronavirus infection has occurred in Hubei province and spread throughout the country quickly. This new crown viral pneumonia was named as coronavirus disease of 2019 (COVID-19) by WHO. However, at present, there is a high incidence of acute aortic dissection in winter and spring. How to prevent the spread of the epidemic and choose the appropriate treatment is an important topic for the patients with acute aortic dissection.Methods:From January 16, 2020 to February 26, 2020, a total of 37 of acute aortic dissection operations were carried out in several cardiovascular surgery centers in Hubei Province. There were 18 cases of Stanford type A aortic dissection and 19 cases of Stanford type B aortic dissection. There were 10 cases (55.55%) with ascending aorta replacement and 7 cases (38.89%) with Bentall procedure for aortic root surgery, and total arch replacement with stented elephant trunk implantation were performed in 14 cases (77.8%). In 19 patients with Stanford type B aortic dissection, thoracic endovascular aortic repair was performed, with the left subclavian artery chimney technique in 2 cases.Results:No deaths occurred within 30 days of hospitalization. Preoperative nucleic acid testing excluded 7 cases of novel coronavirus infection, and 3 suspected cases underwent emergency surgery. the three-level protective standard was adopted in the majority of the surgeries(62.2%, 23/37), and 11 patients were negative in the reexamination of viral nucleic acid after the operation.Conclusion:During the epidemic period, patients with acute aortic dissection should be carefully identified with actife COVID-19 before surgery. The treatment principles-" prevention and control of pneumonia epidemic should be emphasized, conservative medical management should be taken in the comfirmed cases, the selective operation should be delayed as far as possible, and the operation should be reasonable performed in critical cases" should be followed, which can save patients' lives to the greatest extent and prevent the spread of the virus.
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Objective@#To explore the serological and genotypic characteristics of a pedigree with B(A).06 subtype.@*Methods@#Serological methods was used to identify the ABO phenotypes. Exons 6 and 7 of the ABO gene and flanking regions were subjected to direct sequencing and TA clonal sequencing in order to determine the genotype of individuals with inconsistent results for forward and reverse serological typing.@*Results@#Among 12 individuals from 4 generations, 5 were identified with a AwB phenotype, along with a c. 803C>G mutation in exon 7 of the B allele, which was named as B(A).06. The B(A).06/O.01.01 phenotype may be easily missed due to its weak anti-A antibody in the serum upon initial serological test.@*Conclusion@#A B(A).06 subtype family was identified. The serological phenotype of individuals carrying the B(A).06 allele may be affected by the opposite DNA strand.
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OBJECTIVE@#To explore the serological and genotypic characteristics of a pedigree with B(A).06 subtype.@*METHODS@#Serological methods was used to identify the ABO phenotypes. Exons 6 and 7 of the ABO gene and flanking regions were subjected to direct sequencing and TA clonal sequencing in order to determine the genotype of individuals with inconsistent results for forward and reverse serological typing.@*RESULTS@#Among 12 individuals from 4 generations, 5 were identified with a AwB phenotype, along with a c.803C>G mutation in exon 7 of the B allele, which was named as B(A).06. The B(A).06/O.01.01 phenotype may be easily missed due to its weak anti-A antibody in the serum upon initial serological test.@*CONCLUSION@#A B(A).06 subtype family was identified. The serological phenotype of individuals carrying the B(A).06 allele may be affected by the opposite DNA strand.
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Humans , ABO Blood-Group System , Genetics , Alleles , Genotype , Pedigree , Phenotype , Point MutationABSTRACT
Cardiac valve replacement is the most common surgical procedure in cardiac surgery,which often results in non-surgical bleeding.There are many factors that cause non-surgical bleeding after cardiac surgery,which can be summed up as the disease itself,the artificial device of cardiopulmonary bypass and the special requirements during the operation,including the abnormality of liver function,extracorporeal circulation conduits,oxygenators and blood pumps,hypothermia,hemodilution,neutralization between protamine and heparin.At present,most hospitals still use the results of blood loss and coagulation test as the reference for blood transfusion.Only a few hospitals have used thromboelastogram to guide blood transfusion,which is still in the exploratory stage,so far there is no unified reference standard.This review will focus on the related factors leading to non-surgical bleeding and the concept of accurate blood transfusion and reducing blood transfusion after heart valve replacement in order to prevent the occurrence of rethoracotomy to hemostasis.
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OBJECTIVE:To provide reference for rational drug use in clinic and nosocomial infection control. METHODS:Acinetobacter baumannii(AB)were collected from our hospital during Jan. 2014-Jun. 2017. Drug sensitivity tests were conducted by using K-B method and MIC method. Drug-resistance genes of multidrug-resistant Acinetobacter baumannii(MDR-AB)were amplified by PCR,and compared with GenBank database by using Blast comparison. RESULTS:A total of 1 758 strains of AB were detected,and mainly came from sputum and throat swab(65.24%),followed by urine(18.49%). These infected patients were mainly distributed in the departments of ICU(38.51%)and respiratory medicine(24.00%),respectively. Drug resistance of clinical isolated AB to most commonly used antibiotics were more than 40%,such as compound sulfamethoxazole,piperacillin sodium and tazobactam sodium,gentamicin,cefepime,levofloxacin,minocycline,imipenem,etc.;it had increased year after year. Drug resistance to colistin was lower than 5% and decreased year by year.A total of 673 strains of MDR-AB were detected, and detection rates were 22.77%,29.82%,52.09%,54.33%,respectively.Among 110 strains of MDR-AB,detection rates of TEM, AmpC,IMP,VIM,OXA-23,OXA-24,OXA-51,aac(6′)-Ⅰ,aac(3)-Ⅰ,ant(3″)-Ⅰ,anmA,gyrA,parC gene were 97.27%, 91.82%,49.09%,12.73%、90.91%,12.73%,98.18%,34.55%,60.91%,89.09%,87.27%,77.27%,82.73%,respectively. Results of Blast comparison showed that point mutation occurred in 83rd and 121st base of gyrA gene,144th base of parC gene. CONCLUSIONS:AB mainly come from sputum and throat swab specimens in our hospital,and infected patients are mainly distributed in the departments of ICU and respiratory medicine. Drug resistance is serious,and the detection rate of MDR-AB is increased year by year. Main genes of multidrug-resistant strains mainly include TEM,AmpC,OXA-23,OXA-51,ant(3″)-Ⅰ, anmA,etc.,and mutation of gyrA and parC gene are found. It is necessary to strengthen the management of classification use of antibiotics and strengthen the monitoring of AB drug resistance. According to the results of drug sensitivity test,antibiotics are selected rationally to prevent or delay planting and cross transmission of AB-resistant strain.
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Objective To examine the impact of liver cancer patients′ depression, anxiety, psychological distress on demoralization. Methods A cross-sectional survey was conducted among 116 liver cancer patients using Demoralization Scale-Mandarin Version, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Herth Hope Index, Distress Thermometer. Results The average score of demoralization was 33.22 ± 14.85. Analysis of variance showed that the demoralization syndrome′s difference caused by degree of working state, monthly incomewas significant(F=3.795-4.147, P<0.05), correlation analysis showed that patients′demoralization was positively correlated with depression,anxiety, psychological pain,the problems encountered,and negatively correlated with the level of hope(r=0.344-0.601, P<0.01). Multiple regression analysis indicated that working state,depression and hope level explained 50.0％ of the total variance of liver cancer patients′ demoralization. Conclusions Patients with liver cancer have higher levels of demoralization, psycho-physiological symptom can predict it, and the nurses should pay more attention to patients with demoralization.
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Objective To investigate the molecular characteristic of fluoroquinolone resistant Streptococcus agalactiae (GBS) isolates in Suzhou.Methods Totally 46 fluoroquinolone resistant GBS strains were collected,and then subjected into PCR and two resistance genes were sequenced and their high frequency mutation sites,gyrA and parC were analysed.Results Among these isolates,the most frequent gyrA mutation was gyrA_S81L (TCA→TTA),which displayed 93.4％ (43/46) with substituted at No.81 site of amino acid from Ser to Leu.However,the most frequent parC mutation was mutated at No.79 site of amino acid from Ser to Tyr orPhe,with two mutations parC_S79Y (73.9％,34/46) and parC_S79F(17.4％,8/46).The analysis showed that the major mutation patterns are gyrA_S81L with parC_S79Y (73.9％,34/46),gyrA_S81L with parC(13.0％,6/46).Conclusion The most frequent mutations of fluoroquinolone resistant gene in Suzhou are gyrA and parC and the major mutation patterns are gyrA_S81L/parC_S79Y and gyrA_S81L/parC_S79F.
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Malignancy is one of the most important complications of acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV) infection and destruction of host CD4-positive T lymphocytes. Lymphoma ranks first in AIDS-related malignancies. The clinical features of lymphoma patients infected with HIV are different from non-HIV infected patients. The host immune condition in anti-lymphoma chemotherapy also needs to be considered. This paper reviews the clinical characteristics of AIDS-related lymphoma and the attention in anti-lymphoma therapy according to the latest international research findings and related guidelines.
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OBJECTIVE:To compare therapeutic efficacy and safety of chlorquinaldol-promestriene and miconazole nitrate for simple vulvovaginal candidiasis (VCC).METHODS:In retrospective analysis,a total of 231 patients with simple VCC were divided into observation group (116 cases) and control group (115 cases).Observation group was given Chlorquinaldol-promestriene vaginal tablet (0.2 g) every night.Control group was given Miconazole nitrate suppositories (200 mg) every night.Both groups received a course of treatment,lasting for 7 d.Clinical efficacies of 2 groups were observed at the first and second recheck.The symptom relief time recurrence and ADR of effective patients were observed.RESULTS:There was no statistical significance in the total response rates of 2 groups at the first reexamination,as well as total response rates of 2 groups and symptom relief time of effective patients at the second reexamination(P＞0.05).At the second reexamination,reoccurrence rate of observation group was significantly lower than that of control group,with statistical significance (P＜0.05).There was no statistical significance in the incidence of ADR between 2 groups(P＞0.05).CONCLUSIONS:Chlorquinaldol-promestriene is similar to miconazole nitrate for VCC in therapeutic efficacy and safety,but chlorquinaldol-promestriene is better than miconazole nitrate in reducing recurrence rate.
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OBJECTIVE:To compare therapeutic efficacy and safety of chlorquinaldol-promestriene and miconazole nitrate for simple vulvovaginal candidiasis (VCC).METHODS:In retrospective analysis,a total of 231 patients with simple VCC were divided into observation group (116 cases) and control group (115 cases).Observation group was given Chlorquinaldol-promestriene vaginal tablet (0.2 g) every night.Control group was given Miconazole nitrate suppositories (200 mg) every night.Both groups received a course of treatment,lasting for 7 d.Clinical efficacies of 2 groups were observed at the first and second recheck.The symptom relief time recurrence and ADR of effective patients were observed.RESULTS:There was no statistical significance in the total response rates of 2 groups at the first reexamination,as well as total response rates of 2 groups and symptom relief time of effective patients at the second reexamination(P＞0.05).At the second reexamination,reoccurrence rate of observation group was significantly lower than that of control group,with statistical significance (P＜0.05).There was no statistical significance in the incidence of ADR between 2 groups(P＞0.05).CONCLUSIONS:Chlorquinaldol-promestriene is similar to miconazole nitrate for VCC in therapeutic efficacy and safety,but chlorquinaldol-promestriene is better than miconazole nitrate in reducing recurrence rate.
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Objective@#To investigate the genetic characteristics of Lamivudine-resistant mutation patterns and HBV S gene mutants in patients with chronic hepatitis disease of different disease progression.@*Methods@#Blood samples of LAM-resistant patients with chronic hepatitis disease were collected. HBV RT gene nucleotide sequences were obtained, and then differences in drug-resistant mutation patterns, drug susceptibility and HBV S gene mutants characteristics between the two groups were analyzed.@*Results@#Forty-seven chronic hepatitis B (CHB) patients and 16 HBV-related liver cirrhosis (LC)/HBV-related hepatocellular carcinoma (HCC) patients were included in this study. M204I single point mutation and L180M+ M204I/V were the most common pattern during patients with chronic hepatitis disease (35/63, 55.56%). The numbers of resistant to three nucleos(t)ide analogues in LC/HCC group was higher than CHB group’s (62.50% vs 34.04%, P=0.046). In HBV S gene, more immune associated HBsAg-escape mutations were detected in LC/HCC group than that in CHB group (62.50% vs 31.91%, P=0.031). I126T/V and G145A (for LCC/HCC group, 60%), I126S/T and S117T (for CHB group, 46.67%) were showed as the most common form for HBsAg escape mutations in the two groups. The two groups both detected RT mutations concomitantly with stop codon mutations in S gene (rtA181T/sW172* and rtM204I/sW196*).@*Conclusions@#Different characteristics in Lamivudine-resistant mutations and associated HBV S gene mutants were found in patients with chronic hepatitis disease of different disease progression, and LC/HCC patients exhibit more multi-drug resistant variants and immune associated HBsAg-escape mutants than CHB patients.
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Objective To explore the association between toll-like receptor 7 (TLR7) single nucleotide polymorphisms (SNP) and susceptibility of hand, foot and mouth disease caused by enterovirus (EV)71 infection.Methods The genotype of SNP (rs179019 and rs3853839) was determined in 775 EV7l-infected cases (including 439 mild cases and 336 severe cases) and 748 healthy control cases with TaqMan assay.The difference of allele frequencies was compared.The difference of TLR7 mRNA expression in peripheral blood mononuclear cells (PBMCs) derived from different SNP genotype carriers was detected.PBMCs derived from different SNP genotype carriers were stimulated by imiquimod and the TLR7-specific interferon-α(IFN-α) and interleukin-6 (IL-6) secretions were detected.Logistic regression was used to analyze for genotype frequency.Results The frequencies of rs3853839 genotype CC and CG in female patients of severe group were significantly higher than mild group (rs3853839 GC: OR=0.36,95%CI:0.14-0.82, P=0.01;rs3853839 CC: OR=0.19,95%CI:0.11-0.69,P=0.01).In addition, the frequency of rs3853839 genotype C in severe male group was significantly higher compared with that in mild group (OR=0.35,95%CI:0.19-0.63, P=0.01).Female carriers with rs3853839 genotype CC had significantly lower TLR7 mRNA expression than genotype GC and GG (CC vs GG: P=0.005;CC vs GC: P=0.016).Male carriers with rs3853839 genotype C also had significantly lower TLR7 mRNA expression than genotype G (C vs G: P=0.004).After stimulation of imiquimod, the expression of IFN-α (CC vs GG, P=0.001;CC vs GC: P=0.026) and IL-6 productions (CC vs GG: P=0.001;CC vs GC: P=0.011) were significantly lower in female carriers with rs3853839 genotype CC.The same patterns were observed in male carriers with rs3853839 genotype CC (IFN-α: P=0.003;IL-6: P=0.018).Conclusions The rs3853839C allele is the risk factor of severe infection of EV71, which may be due to specific cytokine profiles in rs3853839C allele carriers in children.
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A high performance liquid chromatography method based on amino column to uncover the glycosyls of aroma glycosides in Meili grape was established.Meili grapes were sampled from Yangling, Shaanxi province, China.Aroma glycosides in grape skins were extracted by extraction buffer (0.1 mol/L Na2HPO4/NaH2PO4, pH 7.0, 13% ethanol (V/V)), then enzymatically hydrolysed by AR2000 enzyme preparation in citrate-phosphate buffer (pH 5.0), and the glycosyls liberated were isolated by amino column, and determined by high performance liquid chromatography-refractive index detector (HPLC-RID).The HPLC-RID experimental conditions were developed as follows: amino column temperature 35℃, RID temperature 35℃, injection volume 20 μL, mobile phase acetonitrile/ethyl acetate/water=60∶25∶15 (V/V), flow rate 1 mL/min.The results showed that the reasonable linearity was achieved for rhamnose, xylose, arabinose, apiose and glucose (R2>0.996), with the detection limit (LOD) of 93-123 mg/L and quantitation limit (LOQ) of 309-409 mg/L.The relative standard deviation (RSD, n=10) of the peaks of each monosaccharide (5 g/L) was 2.3%-6.4%, and the recoveries ranged from 73.8% to 125.7%.The molar percentages of the aroma glycosides in Meili grape were 4.1%-6.1% for 6-O-α-L-rhamnopyranosyl-β-D-glucopyranoside, 2.3%-8.8% for 6-O-β-D-xylopyranosyl-β-D-glucopyranoside, 0.1%-3.9% for 6-O-α-L-arabinofuranosyl-β-D-glucopyranoside, 5.5%-9.8% for 6-O-α-L-apiofuranosyl-β-D-glucopyranoside, and 76.3%-86.8% for 6-O-β-D-glucopyranosyl-β-D-glucopyranoside.The contents of each aroma glycoside and the total glycosides in Meili grape didn′t show obvious relationship with berry maturity index during grape maturity.
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Objective To explore the changes of serum IL‐6 ,IL‐10 ,PLA2 on intracranial infection and its prognosis .Methods Totallly 100 patients with intracranial infection during February 2011 to December 2013 were selected as the research object .In 100 cases of intracranial infection patients ,30 cases were cured (group A) and 52 cases improved (group B) ,18 cases of illness or death as poor prognosis group (group C) .Serum IL‐6 ,IL‐10 ,PLA2 content of the subjects in different time point were detected .Results One day After infection ,serum IL‐6 ,IL‐10 ,PLA2 levels in intracranial infection group were obviously higher than that of healthy control group (P< 0 .01) ;7 d after infection ,IL‐6 ,IL‐10 average level among 3 groups had obvious changed(P< 0 .05) ,7 d after in‐fection ,IL‐6 ,IL‐10 level of group B and group C was significantly higher than group A (P< 0 .05) ;and in group C ,IL‐6 ,IL‐10 was higher than group B (P< 0 .05) .7 d after infection ,the IL‐6 IL‐ 10 level of group A declined ,the IL‐6 ,IL‐ 10 levels of group B be‐gan decreasing 14 d after infection ,and the IL‐6 ,IL‐10 levels of group C had been in a rising trend .3 d after infection ,the PLA2 leves among 3 groups had obvious changed(P< 0 .05) ,7 d after infection ,the change rate increased ,7 d after infection ,PLA2 level of group B and group C was significantly higher than group A (P< 0 .05) ,and in group C ,PLA2 was higher than group B (P< 0 . 05) .7 d after infection ,the PLA2 level of group A declined ,in group B and group C ,PLA2 level began to decline significantly 14 d after infection .Conclusion IL‐6 ,IL‐10 ,PLA2 are closely related to the occurrence and prognosis of intracranial infection .
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Objective To construct pET21a-sBAFF by cloning the extracellular regions of 134-285 amino acids of BAFF, a member of human TNF family, and then express the gene in prokaryotic cells and purify the expressed product.Methods cDNA of K562 cell line was used as the template to amplify sBAFF gene to construct pET21a-sBAFF.Expression of sBAFF in E.coli BL21 was induced by IPTG, and the expressed proteins were assayed by SDS-PAGE.The bacteria were analyzed by sonication, and the target proteins mainly existed as inclusion bodies.Then sBAFF was purified by Ni2 +-IDA affinity chromatography.SDS-PAGE electrophoreses displayed that the expressed sBAFF migrated with a relative molecular weight of 18000.ResuIts The induction parameters such as temperature and inducing time were optimized.The target protein accounted for 38.59%of the total bacterial proteins.After refolding, 38.14% of sBAFF proteins were polymerized as an active trimer.The dimer form of sBAFF, which is representative of wrongly refolded product, accounted for very few.ConcIusion The expression and purification of BAFF which formed active trimer after refolding pave the way for its further function study and provide a novel approach for the development of BAFF-targeted therapeutics for autoimmune diseases.
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Combined antiretroviral therapy ( cART) is widely used for infections of human immune deficiency virus ( HIV) .However , some antiviral drugs can not reach the effective concentrations in central nervous system due to the hinder of blood-brain barrier ( BBB) , resulting in the formation of viral reservoir in central nervous system .BBB is formed by human brain microvascular endothelial cells ( HBMVECs ) , which are connected by tight junction and a thick basement membrane , and astrocytic end-feet.This paper reviews possible mechanisms of BBB hindrance and anti-HIV drug efflux by transport proteins , as well as effective methods to deliver antiretroviral drugs into brain , including the application of nano technology .