我国GII.4型诺如病毒Sydney株P颗粒的表达及其组织血型抗原结合特征

目的表达我国新发现GII.4型诺如病毒优势流行株—Sydney株的P颗粒,并探究其结合人类组织血型抗原(HBGAs)受体特征及变化规律。方法扩增SH 2012_05株中的P区域序列,构建进化树分析其氨基酸序列,并在原核表达系统中表达P颗粒。目的重组蛋白经Western blot确定其特异性,并采用ELISA法检测P颗粒结合HBGAs的能力及方式。结果 SH 2012_05毒株P区域与Sydney/2012原型株同源性为99.1%,为GII.4/Sydney基因簇。SDS-PAGE电泳和Western blot分析验证SH 2012_05株P颗粒具有特异性。其结合HBGAs受体方式与以往流行的基因簇一致,即与A、B、O、AB型分泌型唾液均能结合,其中与B型抗原亲和力最高。结论成功表达了我国新发现GII.4型诺如病毒Sydney株的P颗粒,明确了Sydney株能结合分泌型HBGAs受体的特征。本研究为诺如病毒疫苗株选择提供了技术储备,这将为GII.4型诺如病毒的预防和控制提供科学基础。

Current status and emerging challenges in the treatment of hepatitis C virus genotypes 4 to 6

Hepatitis C virus(HCV) genotypes 4, 5 and 6 are mainly present in Africa, the Middle East and Asia and they have been less extensively studied with respect to epidemiology, natural disease history and therapeutic endpoints. Response rates to a 48-wk combined peginterferon/ribavirin treatment range to 40%-69% for HCV 4, 55%-60% for HCV 5 and 60%-90% for HCV 6. Response-guided schedules are recommended to optimize the outcomes of peginterferon/ribavirin treatment in HCV 4 and, in form of preliminarydata, for HCV 6, but no data are yet available to support such an individualization of therapy for HCV 5. Recently, the direct-acting antivirals(DAAs) with pan-genotypic activities simeprevir, sofosbuvir and daclatasvir have been recommended in triple regimens with peginterferon/ribavirin for the treatment of HCV genotypes 4 to 6 infections. In the future, DAA-based interferon-free therapies are awaited to drastically improve treatment outcomes in HCV. However, efforts to improve treatment outcomes with peginterferon/ribavirin should continue, as the HCV 4-6 infected population is mainly based in resource-limited settings with restricted access to the costly DAAs.

Vitamin D deficiency: Correlation to interleukin-17, interleukin-23 and PⅢNP in hepatitis C virus genotype 4

AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type Ⅲ pro-collagen (PⅢNP) as immune response mediators. METHODS: The study was conducted on 50 Egyptian patients (36 male, 14 female) with hepatitis C virus (HCV) infection, who visited the Hepatology Outpatient Clinic in the Endemic Disease Hospital at Cairo University. Patients were compared with 25 ageand sexmatched healthy individuals. Inclusion criteria were based on a history of liver disease with HCV genotype 4 (HCV-4) infection (as new patients or under followup). Based on ultrasonography, patients were classified into four subgroups; 14 with bright hepatomegaly; 11 with perihepatic fibrosis; 11 with hepatic cirrhosis; and 14 with cirrhosis and hepatocellular carcinoma (HCC).Total Vit D (i.e., 25-OH-Vit D) and active Vit D [i.e., 1,25-(OH) 2 -Vit D] assays were carried out using commercial kits. IL-17, IL-23 and PⅢNP levels were assayed using enzyme linked immunosorbent assay kits, while HCV virus was measured by quantitative and qualitative polymerase chain reaction. RESULTS: Levels of Vit D and its active form were significantly lower in advanced liver disease (hepatic cirrhosis and/or carcinoma) patients, compared to those with bright hepatomegaly and perihepatic fibrosis. IL-17, IL-23 and PⅢNP levels were markedly increased in HCV patients and correlated with the progression of hepatic damage. The decrease in Vit D and active Vit D was concomitant with an increase in viral load, as well as levels of IL-17, IL-23 and PⅢNP among all subgroups of HCV-infected patients, compared to normal healthy controls. A significant negative correlation was evident between active Vit D and each of IL-17, IL-23 and PⅢNP (r = -0.679, -0.801 and -0.920 at P < 0.001, respectively). HCV-infected men and women showed no differences with respect to Vit D levels. The viral load was negatively correlated with Vit D and active Vit D (r = -0.084 and -0.846 at P < 0.001, respectively), and positively correlated with IL-17, IL-23 and PⅢNP (r = 0.951, 0.922 and 0.94 at P < 0.001, respectively). Whether the deficiency in Vit D was related to HCVinduced chronic liver disease or was a predisposing factor for a higher viral load remains to be elucidated. CONCLUSION: The negative correlations between Vit D and IL-17, IL-23 and PⅢNP highlight their involvement in the immune response in patients with HCV-4related liver diseases in Egypt.

Treatment of hepatitis C virus genotype 4 with peginterferon alfa-2a: Impact of bilharziasis and fibrosis stage

AIM： To evaluate pegylated interferon alpha2a （PegIFN-α2a） in Egyptian patients with HCV genotype 4, and the impact of pretreatment viral load, co-existent bilharziasis and histological liver changes on response rate. METHODS： A total of 73 nafve patients （61 with history of bilharziasis） with compensated chronic HCV genotype 4 were enrolled into： group A （38 patients） who received 180 mg PegIFN-alpha2a subcutaneously once weekly for a year and group B （35 patients） received IFN alpha-2a 3 MU 3 times weekly. Ribavirin was added to each regimen at a dose of 1200 mg. Patients were followed for 72 wk and sustained response was assessed. RESULTS： Significant improvement in both end of treatment response （ETR） （P 〈 0.002） and sustained response （SR） （P 〈 0.05） was noted with pegylated interferon, where ETR was achieved in 29 （76.3%） and 14 patients （40%） in both groups respectively, and 25 patients in group A （65.8%） and 9 （25.7%） in group B could retain negative viraemia by the end of follow up period. Sustained virological response （SVR） showed a significant negative correlation with age and positive correlation with pretreatment inflammation in patients receiving PegIFN. Viral clearance after 3 mo of therapy was associated with high incidence of ETR and SR （P 〈 0.001）, but without significant difference between both forms of interferon. Significant improvement in response was achieved in patients with high grade fibrosis （grade 3 and 4） with PegIFN-α2a, where SR was seen in 5 out of 13 patients in group A, but none in group B. There was no significant difference in response between bilharzial and non-bilharzial patients in both groups. In terms of safety and tolerability, neutropenia was the predominant side effect, both drugs were comparable. CONCLUSION： PegIFN-~2a combined with ribavirin results in improvement in sustained response in HCV genotype 4, irrespective of history of bilharzial infestation.

Interleukin-28 and hepatitis C virus genotype-4:Treatment-induced clearance and liver fibrosis

AIM:To investigate the association between interleukin-28B(IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus(HCV) genotype 4.METHODS:Two hundred and one HCV-genotype 4 patients were included.All patients were treated with Peginterferon alph2a/Ribavirin for 48 wk.End of treatment response(ETR) was defined as loss of detectable serum HCV RNA at the end of treatment.Sustained viral response(SVR) was defined as loss of detectable serum HCV RNA at the end of 24 wk follow up.Genotyping of IL28B rs12979860 was performed using the TaqMan assay.We used logistic regression to estimate the adjusted odds ratio(aOR) and 95%CI.RESULTS:The study included 201 HCV-genotype 4 patients.The majority of patients were men(89.6%),with a median age of 47 years,inter-quartile range(40-51).Approximately 62.5% of patients had ETR,and 49.6% had SVR.Individuals who achieved SVR were more likely to be younger(χ 2 = 4.91,P = 0.027),and less likely to have fibrosis(χ 2 = 15.54,P < 0.0001),or inflammation(χ 2 = 7.58,P = 0.006).The genotype distribution of rs12979860 was 36.2%,49.0% and 14.8% for genotypes CC,CT,and TT,respectively.In these participants,rs12979860 genotype distribution did not differ by gender(P = 0.466),pretreatment viral load(P = 0.600),inflammation(P = 0.435),or fibrosis(P = 0.291).The frequencies of IL28B rs12979860 genotypes were TT(14.8%),CT(49.0%),and CC(36.2%).Compared to rs12979860 genotype TT,aORs(95%CI) for ETR and SVR were:CC genotype,[17.55(5.34-57.69) and 5.92(2.09-16.76),respectively];CT genotype,[5.15(1.80-14.78) and 2.48(0.94-6.52),respectively].In the current study,the patients who did not achieve ETR or SVR had a lower prevalence of rs12979860 CC(17.4% and 23.3%,respectively) than individuals who had ETR or SVR(47.9% and 47.2%,respectively).Individuals with rs12979860 CC genotype had approximately 6 times the odds of SVR compared to individuals with TT genotype(aOR = 5.92;95%CI:2.09-16.76).Similarly,patients with CT genotype had SVR more often than patients with TT genotype(aOR = 2.48;95%CI:0.94-6.52).Carrying at least one copy of the C allele(genotypes CT and CC) had almost 8 times the probability of ETR compared to those with genotype rs12979860 TT(aOR = 7.87;95%CI:2.84-21.82),and approximately 3 times the odds of SVR compared to those with genotype rs12979860 TT(aOR = 3.46;95%CI:1.37-8.74).In addition,data were consistent with a significant gene-dose relationship(aOR = 4.05/allele;95%CI:2.27-7.22).The association between rs12979860 genotype and SVR was similar among those who achieved and those who did not achieve SVR.CONCLUSION:In HCV-genotype 4 patients,rs12979860 is a sensitive predictor of viral clearance,independent of viral load,age,gender or fibrosis,with no similar relation to severity of fibrosis.

Assessment of co-segregated TLR4 genotypes among Nigerian children with asymptomatic and clinical malaria

Objective: To assess the occurrence and pattern of Toll-like receptor 4(TLR4) cosegregated genotypes among children with Plasmodium falciparum malaria in Nigeria.Methods: In this case-control study, a total of 79 Plasmodium falciparum infected children aged 2–7 years and 105 age-matched uninfected controls of Yoruba descents in Lagos were studied. The extracted DNA samples were used for TLR4 genotyping at codons 299(Asp > Gly) and 399(Thr > Ile) by PCR-restriction fragment length polymorphism. Malaria infection was diagnosed by blood smear microscopy and infected children were stratified into asymptomatic, uncomplicated and severe malaria sub-groups.Malnutrition was determined by measuring the mid upper arm circumference and anemia was defined as hemoglobin < 11 g/dL.Results: The proportions of children with acute malnutrition and severe anemia were12.0% and 3.2%, respectively. Parasitemia and malnutrition were not correlated and four distinct patterns of TLR4 genotypes were found in the study population: Asp299Asp/Thr399Thr(90.2%), Asp299Gly/Thr399Thr(4.3%), Gly299Gly/Thr399Thr(3.8%) and Asp299Gly/Thr399Ile(1.6%). These genotypes did not differ significantly(P > 0.05) in frequency between infected and non-infected children. However, low and high occurrences of the TLR4 Asp299Asp/Thr399 Thr and Asp299Gly/Thr399 Thr genotypes were observed in the severe malaria subgroup.Conclusions: This study reveals a protective role for TLR4 Asp299Gly/Thr399 Ile and Asp299Asp/Thr399 Thr genotypes against severe malaria in Nigerian children.

Interferon-free treatments in patients with hepatitis C genotype 1-4 infections in a real-world setting

AIM To investigated the real-world effectiveness and safety of various regimens of interferon-free treatments in patients infected with hepatitis C virus(HCV).METHODS We performed an observational study to analyze different antiviral treatments administered to 462 HCV-infected patients, of which 56.7% had liver cirrhosis. HCV RNA after 4 wk of treatment and at 12 wk after treatment sustained virologic response(SVR) as well as serious adverse events(SAEs) was analyzed first for the whole cohort and then separately in patients who met or did not meet the inclusion criteria of a clinical trial(CT-met and CT-unmet, respectively).RESULTS The most frequently prescribed treatment was simeprevir/sofosbuvir(36.4%), followed by sofosbuvir/ledipasvir(24.9%) and ombitasvir/paritaprevir/ritonavir(r)/dasabuvir(19.9%). Ribavirin(RBV) was administered in 198 patients(42.9%). SVRs occurred in 437/462 patients(94.6%). The SVRs ranged between 93.3% and 100% for genotypes 1-4. SVRs were achieved in 96.2% patients in the CTmet group vs 91.9% patients in the CT-unmet group(P = 0.049). Undetectable HCV RNA at week 4 occurred in 72.9% of the patients. In the univariate analysis, the factors associated with SVRs were lower liver stiffness, absence of cirrhosis, higher platelet count, higher albumin levels, no RBV dose reduction, undetectable HCV RNA at week 4 and CT-met group. In the multivariate analysis, only albumin was an independent predictor of treatment failure(P = 0.04). Eleven patients(2.4%) developed SAEs; 5.2% and 0.7% of the patients in the CT-unmet and CT-met groups, respectively(P = 0.003).CONCLUSION A high proportion of patients with HCV infection achieved SVRs. For patients who did not meet the CT criteria, treatment regimens must be optimized.

Sustained virological response in a predominantly hepatitis C virus genotype 4 infected population

AIM:To assess sustained virological response(SVR) rates in a predominantly hepatitis C virus(HCV) genotype 4 infected population. METHODS:Between 2003-2007,240 patients who were treated for chronic hepatitis C infection at our center were included.Epidemiological data,viral genotypes,and treatment outcomes were evaluated in all treated patients.Patients with chronic renal failure, previous non-responders,and those who relapsed after previous treatment were excluded from the study.Among all patients,57%were treated with PEG-interferon(IFN)α-2a and 43%patients were treated with PEG-IFNα-2b;both groups received a standard dose of ribavirin. RESULTS:89.6%of patients completed the treatment with an overall SVR rate of 58%.The SVR rate was 54%in genotype 1,44%in genotype 2,73%in genotype 3,and 59%in genotype 4 patients.There was no statistical difference in the SVR rate between patients treated with PEG-IFNα-2a and PEG-IFNα-2b (61.5%vs 53%).Patients younger than 40 years had higher SVR rates than older patients(75%vs 51%,P =0.001).SVR was also statistically significantly higher when the HCV RNA load(pretreatment)was below 800.000(64%vs 50%,P=0.023),in patients with a body mass index(BMI)less than 28(65%vs 49%,P =0.01),and in patients who completed the treatment duration(64%vs 8%,P≤0.00001).CONCLUSION:The SVR rate in our study is higher than in previous studies.Compliance with the standard duration of treatment,higher ribavirin dose,younger age,lower BMI,and low pretreatment RNA levels were associated with a higher virological response.

Impact of past HBV exposure on virological response to combined interferon ribavirin therapy in patients with chronic HCV genotype 4

Aim: is to investigate if past exposure to HBV in chronic HCV infection promotes the progression of liver disease and influences Interferon (INF) response or not. Methods: 185 patients with chronic HCV were recruited and randomized into 2 groups, group I was treated with PEG-IFN alfa-2b plus ribavirin and group II with 3 MU/TIW IFN alfa-2b plus ribavirin. All patients had HBsAg negative & patients had HBc Ab positive tested for HBsAb. Patients with HBc Ab (n = 37) were tested for serum HBV DNA. Pretreatment liver biopsy and Immunohistochemistry was performed for detection of HBsAg and HBcAg using monoclonal antibodies. Demographic and laboratory data were collected. Results: 70/185 (38%) patients had Anti-HBc, 37 (20%) had isolated anti-HBc and none of the 37 subjects with isolated anti-HBc had serum HBV DNA. Sustained Viral Response (SVR) was achieved in 32/70 (46%) and 46/115 (40%) in anti-HBc seropositive and seronegative patients respectively, in conventional IFN group SVR was 37% and 39% in past HBV exposed patients and unexposed respectively, in PEG IFN group SVR was 59% and 41% in past HBV exposed patients and unexposed respectively. Among anti-HBc and anti-HBs seropositive patients SVR was 10/12 [83%] and 4/21 [19%] p = 0.004 in PEG and conventional IFN respectively. Marked fibrosis was diagnosed in 20% past HBV exposed patients versus 10% in unexposed patients (p = 0.01). Conclusion: past HBV exposure promotes the progression of liver disease but has no effect on the SVR to antiviral therapy in chronic HCV genotype 4 patients.

Insulin Resistance, Visceral Adiposity Index and TyG Index in Genotype-4 Chronic HCV Patients and Their Relation to Hepatic Histopathology

Introduction: Hepatitis C virus (HCV) genotype 4 is the most prevalent in Egypt. Vis-ceral adiposity index (VAI) and (TyG) index are newly developed indices for assess-ment of metabolic syndrome (MS) and insulin resistance (IR). We aimed at comparing their levels in HCV-patients with healthy controls and validate their use for prediction of hepatic histopathological changes. Patient and Methods: 78 chronic HCV-infected patients proven by PCR, viral genotyping and hepatic histopathology, and 67 healthy controls were enrolled. Presence of MS, Homeostasis Model Assessment for IR esti-mation (HOMA-IR), TyG index, and VAI were assessed. Results: HOMA-IR, TyG and frequency of MS were significantly higher in patients’ group (p p p = 0.002). Conclusion: HCV genotype 4 is significantly associated with MS and increased values of HOMA IR and TyG index. TyG index and VAI are valuable simple indices that could predict the histopathological changes in Egyptian CHC pa-tients.

The complete genomic sequence analysis of genotype 4 human astrovirus HASTVgz01 strain in Guangzhou

To analyze the genomic molecular structure and genotype of human astrovirus isolated from infant in Guangzhou of China, the primers were designed based on the genomic sequence of astrovirus from the C, enBank and the target sequence were amplified by RT-PCR. Then the PCR-products were cloned to T vector and sequenced. The genomic nucleotide sequences were analyzed by the programs CLUSTAL W and DNASTAR. It was found that the full genomic length of HASTVgz01 strain was 6721 bp and the ORFs were 6558 bp. The 5＇ and 3＇UTR were 82 and 81 nucleotides. The genome included 3 open reading frames （ORFs） ： ORFla, ORFlb and ORF2. The 5＇-terminal ORFla started at nueleotide 83 and extended to nucleotide 2845. ORFlb （nt 2785 to nt 4332） overlaped ORFla by 61 nueleotides. The 3＇-terminal ORF2 began at nucleotide 4325 and terminated at nucleotide 6640. ORF2 had 2316 nucleotides. Compared with other astrovirus sequences in GenBank, the homology of the amino acid sequence of ORF2 of HASTVgz01 strain with that of serotype 4 was 93%. Homology with other serotypes ranged from 61% to 70%. The complete nucleotide sequence of astrovirus HASTVgz01 strain isolated from Guangzhou in China was 6721 bp in length, GenBank accession NO. DQ344027. Comparing the ORF2 of astrovirus HASTVgz01 with the known sequences of types 1-8 the highest homology was serotype 4 （93%）. Comparative sequence analysis of the HASTVgz01 ORF2 with the reported human astrovirus sequences revealed that the isolated astrovirus belongs to genotype （serotype） 4.

慢性戊型肝炎的诊治进展

据世界卫生组织估计,戊型肝炎病毒(hepatitis E virus,HEV)每年全球约有2000万例的新发感染,可能导致超过300万例急性肝炎。我国是戊型病毒性肝炎(戊肝)高流行区,近年来戊肝发病人数已超过甲型病毒性肝炎(甲肝)。戊肝发病率从2010年的1.77/10万上升至2019年的2.02/10万。我国HEV感染途径主要为食源性感染。慢性HEV感染是指患者感染HEV后,血或粪便中病毒核酸持续阳性3个月以上,其多发生于免疫低下人群,并可能导致患者出现肝纤维化和肝硬化的快速进展。我国以HEV 4型感染为主,因此我国慢性戊肝患者感染的病毒也主要为HEV 4型。HEV感染诊断主要依据特异性HEV抗体或病原学指标。HEV感染筛查应着重关注基础肝病患者、育龄期妇女和老年人及免疫缺陷患者(如器官移植患者、血液肿瘤患者、HIV感染者)等。戊肝诊治中仍然存在很多问题,包括慢性戊肝患者肝纤维化快速进展的危险因素尚未明确;老年男性和孕妇感染HEV后易出现重症的机制有待研究;抗HEV药物筛选多为体外细胞模型的结果,治疗药物仍处于临床前研究阶段。今后应聚焦戊肝的发病机制研究,推动基础研究和临床研究的交叉、融合与转化,为慢性戊肝诊治的药物治疗提供更多有效方案。

云南登革4型病毒的鉴定及NS1和NS2a基因序列分析

目的对1989年8月分离自云南省盈江县蚊虫的2株登革病毒进行生物学及分子特征的鉴定,明确这两株病毒的血清型及基因型。方法蚊虫用BHK21细胞和乳鼠法分离病毒,用间接免疫荧光试验、RT-PCR等方法进行鉴定,并对这两株病毒的分子生物学特征进行分析。结果从白纹伊蚊和达勒姆阿蚊中各分离到一株病毒,分别命名为M110和M113,这两株病毒对BHK21细胞能产生明显的细胞病变,脑内接种乳鼠4d左右导致乳鼠死亡。该病毒经血凝、血凝抑制和间接免疫荧光试验提示为黄病毒。分别用黄病毒属特异引物、登革4型病毒NS1和NS2a基因片段特异引物进行RT-PCR扩增、序列测定,证实为登革4型病毒。NS1和NS2a基因序列片段分析表明,M110和M113的NS1核苷酸序列与登革4型病毒基因Ⅰ型的H241株(Y19176)同源性最高,分别为99%、98%;NS2a基因片段与H241的核苷酸序列的同源性分别为96.5%、97.1%。结论从盈江县蚊虫分离到的M110和M113病毒为登革4型病毒基因Ⅰ型,表明云南省西部边境地区在20世纪80年代发生过登革4型病毒的流行。

广东汉族人群磷酸二酯酶4D基因多态性与缺血性脑卒中的关系

目的探讨广东汉族人群磷酸二酯酶4D基因(phosphodiesterase 4D,PDE4D)单核苷酸多态性(single nucleotide polymorphism,SNP)与缺血性脑卒中的关系。方法采用病例-对照的研究方法,选择广东地区712例缺血性脑卒中患者作为病例组,另选择同期健康体检的广东居民774例作为对照组。根据TOAST分型将病例组又分为大动脉粥样硬化型327例、小动脉闭塞型221例、心源性栓塞型54例、其他明确病因型52例和不明原因型58例。使用SNaPshot方法对PDE4D基因SNP83多态性进行检测,并分析SNP83多态性与缺血性脑卒中及其5个亚型之间的关系。结果病例组与对照组SNP83的CC、CT和TT基因型分布比较,差异无统计学意义(2.9%vs2.3%,29.1%vs 26.2%,68.0%vs 71.4%,P>0.05)。在显性、隐性及加性3种遗传模型下,PDE4D基因SNP83多态性与病例组及5个亚型均无相关性。结论 PDE4D基因SNP83多态性与广东汉族人群缺血性脑卒中不相关。

浙江南部地区人群5-脂氧合酶激活蛋白和磷酸二酯酶4D基因突变与缺血性脑卒中的研究

目的为探索浙江南部地区人群5-脂氧合酶激活蛋白(ALOX5AP)基因中SG13S89、SG13S114和磷酸二酯酶4D(PDE4D)基因中单核苷酸多态性83与缺血性脑卒中的关系。方法选择脑梗死患者394例为脑梗死组,另选无脑梗死382例为对照组。采用PCR和基质辅助激光解析/电离飞行时间质谱法,分析ALOX5AP基因中的SG13S89(rs4769874)、SG13S114(rs10507391)和PDE4D基因中单核苷酸多态性83(rs966221)的多态性。结果与对照组比较,脑梗死组SG13S89基因AG型、A等位基因频率明显升高(4.1%vs 1.3%,P<0.05;2.0%vs0.7%,P<0.05);。多因素logistic回归分析显示,调整高血压、糖尿病和年龄后,SG13S89的AG基因型相对于GG基因型有较高的脑卒中风险(OR=4.24,95%CI:1.17～15.32,P=0.027)。SG13S89等位基因分布与大动脉粥样硬化型和小动脉闭塞型脑梗死差异无统计学意义(P>0.05)。SG13S89的AG基因型与女性人群发生脑卒中相关(P=0.022),但A等位基因在女性脑卒中人群中差异无统计学意义(P>0.05)。结论 rs4769874AG基因型和A等位基因频率可增高缺血性脑卒中风险,可能是该基因与血管炎性反应和通透性增加导致脑梗死的机制相关。但未发现PDE4D基因单核苷酸多态性83突变与脑卒中相关。

白细胞介素4受体基因多态性与变应性鼻炎的相关性

目的通过研究白细胞介素4受体(interleukin–4,IL-4R)基因多态性与变应性鼻炎的相关性,探讨IL-4Rα链上Q576R位点基因多态性与变应性鼻炎发病之间的关系。方法采用聚合酶链反应——限制性片段长度多态性分析法(PCR-RFLP)检测50例变应性鼻炎患者(病例组)和40例健康人群(对照组)的IL-4Rα链上Q576R位点基因多态性,比较两组的基因型和等位基因的分布频率,并计算基因优势比(OR)。结果病例组和对照组R576和Q576等位基因分布频率的差异具有显著性(x2=9.12,P<0.01),病例组中R576等位基因分布频率显著高于对照组。R576携带者发生变应性鼻炎的相对危险度是Q576的4.66倍(OR=4.66,x2=9.98,P<0.01)。结论IL-4Rα链上Q576R位点基因多态性与变应性鼻炎有相关性,提示Q576R多态性可能在决定变应性鼻炎遗传易感性方面有重要作用,是变应性鼻炎的一个易感候选基因。

ApoEε4基因结合sMRI对不同亚型轻度认知功能障碍的研究

目的评价4种不同轻度认知障碍亚型之间人口统计学、心理特点、结构性磁共振成像(structural magnetic resonance imaging,s MRI)及载脂蛋白Eε4(apolipoprotein Eε4,ApoEε4)的特点。方法对94例轻度认知障碍的老年人,与53例认知程度正常老年人作为对照组进行评价。4种轻度认知障碍(mild cognitive impairment,MCI)基于神经心理学表现分类,颞叶内侧面萎缩(medial temporal lobe atrophy,MTA)和脑白质高信号(white matter hyperintensity,WMH)通过s MRI评估。另外,研究简易精神状态检查表(Minimum Mental State Examination,MMSE)评分、MTA评分、WMH和MCI亚型间与ApoEε4关系。通过s MRI评估。结果在不同亚型的MCI及对照组之间其MMSE评分、MTA差异有统计学意义,遗忘型轻度认知障碍(amnestic MCI,a MCI)亚型与非遗忘型轻度认知障碍亚型(non-amnestic MCI,na MCI)相比,MTA评分明显增加。然而,WMH无明显差异。ApoEε4基因在a MCI及na MCI亚型中显著增加。结论 MCI不同亚型可显示生物异质性,s MRI结合ApoEε4可以协同预测MCI向痴呆的发展。

磷酸二酯酶4D基因rs966221位点单核苷酸多态性与缺血性脑卒中发病的关系

目的探讨广西壮族人群磷酸二酯酶4D(PDE4D)基因rs966221位点单核苷酸多态性与缺血性脑卒中(IS)发病的关系。方法采用病例-对照研究设计,运用SNaPshot技术对101例广西壮族IS患者(IS组)及同期104例健康体检者(对照组)的PDE4D基因rs966221位点单核苷酸多态性进行检测,比较2组各基因型及等位基因频率,并进行相关性分析。结果 IS组与对照组PDE4D基因rs966221位点GG、GA、AA基因型(0.99%vs 3.85%,29.70%vs 21.15%,69.31%vs 75.00%)及G、A等位基因频率(15.84%vs 14.42%,84.16%vs 85.58%)比较,差异无统计学意义(P>0.05)。单因素及多因素logistic回归分析显示,在显性(AAvs GG+GA)、隐性(GGvs AA+GA)和加性(GGvs AA)3种遗传模型下,PDE4D基因rs966221位点单核苷酸多态性与IS患病风险均无关联(P>0.05)。结论广西壮族人群PDE4D基因rs966221位点单核苷酸多态性与IS发病不相关。

慢性丙型肝炎患者血清IL-4、IFN-γ水平与病毒基因型、病毒量等抗病毒治疗影响因素的关系

本研究检测了64例慢性丙型肝炎(CHC)患者的血清HCV RNA基因型、IFN-γ和IL-4水平、HCV-RNA含量以及ALT水平。结果显示CHC患者血清IFN-γ水平在1b型的患者显著低于2 a型(P<0.05),与病毒载量、ALT水平等均无显著性相关(均为P>0.05)。在同一基因型中,血清IL-4、IFN-γ水平与ALT水平、病毒载量亦无相关(P>0.05)。在同一基因型中,血清IL-4、IFN-γ水平与ALT水平、病毒载量亦无相关(P>0.05):在诸多抗病毒影响因素中,病毒基因型在血清IFN-γ水平上具有差别,提示1b型较其他基因型为低的IFN-γ水平可能是该型更易发生HCV持续感染的因素之一。

1,2,4-三氯苯胁迫对不同基因型水稻灌浆期生理特性及产量的影响

在盆栽土培条件下,研究了5种浓度(0、10、20、40、80 mg/kg土)的1,2,4-三氯苯(TCB)对两种基因型水稻品种宁粳1号(敏感基因型)和扬辐粳8号(耐性基因型)产量及灌浆期生理特性的影响。结果表明:TCB对两种基因型水稻产量和灌浆期生理特性的影响具有显著差异,随着TCB浓度的增加,宁粳1号的产量呈现递减趋势,而扬辐粳8号呈低浓度下产量增加高浓度下产量显著降低的趋势,在中高浓度TCB(40、80 mg/kg)处理时,宁粳1号每盆穗数,每穗粒数,结实率显著降低且降幅显著大于扬辐粳8号,两个基因型品种千粒重变化都不明显。宁粳1号株高、干物重受TCB抑制程度较明显,降幅显著大于扬辐粳8号。在低浓度TCB(20 mg/kg)处理时,宁粳1号根系活力、叶绿素含量、可溶性蛋白质含量显著降低,而扬辐粳8号有所提高。随着TCB浓度的增加,两个基因型品种叶片抗氧化酶SOD、POD、CAT活性均呈先升后降趋势,且在低浓度TCB(10 mg/kg、20mg/kg)处理时,扬辐粳8号抗氧化酶活性极显著高于宁粳1号,在高浓度TCB(80 mg/kg)TCB浓度胁迫下,宁粳1号抗氧化酶活性极显著低于对照,且降幅极显著大于扬辐粳8号,且MDA含量增幅较大,膜质过氧化程度高。总体而言,低浓度TCB对扬辐粳8号的产量和灌浆期株高、干物重、叶绿素含量、叶片蛋白质含量和抗氧化酶活性具有一定的促进作用,中高浓度TCB对宁粳1号的抑制作用显著大于扬辐粳8号,扬辐粳8号在不同浓度的TCB处理下较宁粳1号表现出较强的耐迫性和适应性。