简介:AbstractBackground:Immune- and inflammation-related genes (IIRGs) play an important role in the pathogenesis of tuberculosis (TB). However, the relationship between IIRG polymorphisms and TB risk remains unknown. In this study, the gene polymorphisms and their association with tuberculosis were determined in a Chinese population.Methods:We performed a case-control study involving 1016 patients with TB and 507 healthy controls of Han Chinese origin. Sixty-four single-nucleotide polymorphisms (SNPs) belonging to 18 IIRGs were genotyped by the PCR-MassArray assay, and the obtained data was analyzed with χ2-test, Bonferroni correction, and unconditional logistic regression analysis.Results:We observed significant differences in the allele frequency of LTA rs2229094*C (P = 0.015), MBL2 rs2099902*C (P = 0.001), MBL2 rs930507*G (P = 0.004), MBL2 rs10824793*G (P = 0.004), and IL12RB1 rs2305740*G (P = 0.040) between the TB and healthy groups. Increased TB risk was identified in the rs930507 G/G genotype (Padjusted = 0.027) under a codominant genetic model as well as in the rs2099902 (C/T + C/C) vs T/T genotype (Padjusted = 0.020), rs930507 (C/G + G/G) vs C/C genotype (Padjusted = 0.027), and rs10824793 (G/A + G/G) vs A/A genotype (Padjusted = 0.017) under a dominant genetic model after Bonferroni correction in the analysis of the overall TB group rather than the TB subgroups. Furthermore, the rs10824793_rs7916582*GT and rs10824793_rs7916582*GC haplotypes were significantly associated with increased TB risk (P = 0.001, odds ratio [OR] = 1.421, 95% confidence interval [CI]: 1.152-1.753; and P = 0.018, OR = 1.364, 95% CI: 1.055-1.765, respectively). Moreover, the rs10824793_rs7916582*AT/AT or rs10824793_rs7916582*GT/GT diplotype showed a protective (P = 0.003, OR = 0.530, 95% CI: 0.349-0.805) or harmful (P = 0.009, OR = 1.396, 95% CI: 1.087-1.793) effect against the development of TB.Conclusions:This study indicated that MBL2 polymorphisms, haplotypes, and diplotypes were associated with TB susceptibility in the Han Chinese population. Additionally, larger sample size studies are needed to further confirm these findings in the future.
简介:摘要:目的 对脑梗死合并 2型糖尿病的临床诊治情况进行分析。方法 选取我院 2019年 1月至 2020年 2月间收治的脑梗死合并 2型糖尿病患者共 50例,将其设定为观察组,同期选取 50例脑梗死患者,将其设定为对照组,对比两组医学影像检查结果、血浆相关指标结果及治疗效果。结果 经头颅 CT和 MRI检查发现,观察组中单发性脑梗死 10例,腔隙性脑梗死 29例,多发性脑梗死 11例,对照组分别占 32例、 8例、 10例 ,两组数据差异较大,( P< 0.05)。观察组和对照组的总胆固醇、甘油三酯、高密度脂蛋白、全血低且还原黏度相比,数据差异较大,( P< 0.05)。观察组和对照组的治疗总有效率分别为 XX,数据差异大,( P< 0.05)。结论 临床采用头颅 CT和 MRI联合诊断脑梗死合并 2型糖尿病,利于疾病的治疗,此外,只有严格控制患者血糖水平、血脂黏度,才能提升疾病治疗效果。
简介:摘要目的探讨中心体相关蛋白激酶2(NEK2)和环氧合酶2(COX2)在前列腺癌组织的表达及两者与前列腺癌临床病理参数的关系。方法选取广东医科大学附属医院2013年2月至2019年9月收治的77例前列腺癌组织标本和27例前列腺增生组织标本作为研究对象,应用免疫组织化学法检测两者组织中NEK2和COX2的表达水平,结合临床资料进行相关统计学分析。各组间比较采用t检验。结果前列腺癌组织中的NEK2表达率明显高于前列腺增生组织NEK2表达率(61.43%比20.00%,t= 10.702,P<0.01),NEK2表达水平与前列腺癌组织学分级、临床分期明显相关(t=8.901、9.848,P<0.05);前列腺癌组织中的COX2表达率明显高于前列腺增生组织COX2表达率(64.29%比15.00%,t= 15.182,P<0.01),COX2表达水平与前列腺癌组织学分级、精囊腺侵犯、临床分期明显相关(分别为t=9.043、4.400、10.536,P<0.05)。结论NEK2和COX2在前列腺癌组织中高表达,检测NEK2和COX2有助于判断前列腺癌患者恶性程度。
简介:AbstractObjective:In order to study the important role and molecular mechanism of Brevinin-2 family antimicrobial peptide Brevinin-2ISb in methicillin-resistant Staphylococcus aureus (MRSA) infection of Caenorhabditis (C.) elegans, and to find the optimal therapeutic concentration of Brevinin-2ISb.Methods:By using a C. elegans model and MRSA infection modelto study the therapeutic effect of different concentrations of Brevinin-2ISb on C. elegans. Real-time PCR was used for investigating the effect of Brevinin-2ISb on the downstream gene expression of DAF-2/DAF-16 innate immune pathway and the major virulence factor gene expression of MRSA. With protein activity tests to study the inhibitory effect of Brevinin-2ISb on MRSA virulence factor protein activity. Finally, laser confocal imaging was carried out to observe real-time expression and distribution of downstream antimicrobial proteins to further prove the effect of Brevinin-2ISb on the activation of DAF-2/DAF-16 pathway by in vivo imaging. All animal study procedures were approved by the Academic Committee at Xidian University and Xi’an Jiaotong University Animal Care and Use Committee, China (approval No. JGC201207) on July 15, 2017.Results:Host immunity was largely enhanced by Brevinin-2ISb, and the expression of staphylococcal enterotoxin genes, as well as virulence factors, was suppressed by Brevinin-2ISb. Indeed, the expression of many C. elegans innate immune genes, including lys-7, spp-1, K05D8.5 and C29F3.7, was induced by Brevinin-2ISb. In particular, robust, sustained expression of the antibacterial gene lys-7 was observed after Brevinin-2ISb treatment, resulting in increased protein levels. These effects correlated with a reduction in the MRSA-mediated death of the C. elegans host. Low concentrations of Brevinin-2ISb exhibited very low hemolytic activity, and may play a positive role in host innate immunity. Specifically, activation of the DAF-2/DAF-16 pathway appears to be essential for immune activation in C. elegans treated with Brevinin-2ISb. Based on the evolutionary conservation of innate immune pathways, our results suggest that Brevinin-2ISb not only has strong antibacterial activity, but may also enhance the innate immune response in humans. This study demonstrates that Brevinin-2ISb-related peptides are potential candidates for the development of novel anti-inflammatory or anti-microbial drugs.Conclusion:Antimicrobial peptide Brevinin-2ISb effectively inhibits MRSA at low concentration. This antimicrobial peptide can prolong the life of MRSA-infected C. elegans, has very low hemolytic activity and inhibits the activity and expression of various MRSA virulence factors. More importantly, Brevinin-2ISb activated the expression of antimicrobial genes downstream of DAF-2/DAF-16, which enhanced the MRSA resistance of C. elegans. This peptide could be used as the basis for developing new drugs to replace antibiotics.
简介:摘要目的研究基质金属蛋白酶组织抑制因子(TIMP)-1 siRNA、TIMP-2 siRNA对CCl4诱导的肝纤维化大鼠肝星状细胞(HSC)中smad 2/3/4蛋白表达的影响。方法采用前期构建的TIMP-1 siRNA、TIMP-2 siRNA治疗后肝纤维化大鼠的肝脏组织作为研究对象,用免疫组织化学、蛋白质印迹法(Western blot)及Real-time PCR法检测smad2、smad3、smad4的蛋白表达和相应的mRNA表达水平,并用正置荧光显微镜计数免疫荧光双标记TUNEL阳性细胞和α-平滑肌肌动蛋白(α-SMA)阳性细胞。多组间均数比较采用ANOVA方差分析,均数两两比较采用SNK检验。结果免疫组织化学结果显示TIMP-1 siRNA组、TIMP-2 siRNA组中smad2、smad3、smad4的蛋白表达量较模型组、阴性对照组明显减少(P值均< 0.05)。Western blot结果也显示相同趋势,TIMP-1siRNA组、TIMP-2siRNA组中smad2、smad3、smad4的蛋白表达量较模型组、阴性对照组显著减少(P值均< 0.01)。TIMP-1siRNA组、TIMP-2siRNA组smad2、smad3、smad4的mRNA表达量较模型组、阴性对照组明显减少(P值均< 0.05)。免疫荧光显示TIMP-1 siRNA组(0.014 3±0.002 4)、TIMP-2 siRNA组(0.010 7±0.004 4)活化HSC的凋亡指数较模型组(0)、阴性对照组(0.002 4±0.002 4)增加(P值均< 0.05)。结论TIMP-1 siRNA、TIMP-2 siRNA促进了活化HSC的凋亡,对smads蛋白的表达量有明显抑制作用。
简介:摘要2例患者(例1女,63岁;例2男,22岁)分别因肺腺癌和滑膜肉瘤应用安罗替尼治疗。例1服用安罗替尼(12 mg口服、1次/d,治疗2周停用1周为1个周期)8个周期后出现咳嗽、咳痰伴呼吸困难,经胸部CT检查诊断为自发性气胸。考虑气胸与安罗替尼有关。停用该药,予胸腔闭式引流等治疗后呼吸困难缓解。因病情进展,患者减量服用安罗替尼(10 mg/d,用法同前),第1个周期中再次发生自发性气胸。终止安罗替尼治疗,予以胸腔闭式引流、祛痰、抗感染及营养支持等治疗,10 d后行胸部X线检查示气胸痊愈。例2服用安罗替尼(12 mg/d,用法同例1)9个周期后出现自发性气胸(经胸部CT检查发现),但患者无明显不适,在密切监测呼吸状况下继续使用安罗替尼。
简介:摘要严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)属于β冠状病毒,其通过表面刺突蛋白(spike protein, S蛋白)以血管紧张素转换酶2(angiotensin-converting enzyme 2, ACE2)作为受体介导膜融合入侵宿主细胞。感染过程中造成的功能性ACE2水平下降通过影响肾素血管紧张素系统(renin-angiotensin system, RAS)的平衡造成肺部损伤。感染SARS-CoV-2的部分重症感染患者中,机体先天和适应性免疫机制的失衡而形成的细胞因子风暴,可导致急性呼吸窘迫综合征(acute respiratory distress syndrome, ARDS)及全身多器官功能脏器衰竭。适应性免疫的失衡所致淋巴细胞总数的降低,并与不良预后相关。
简介:[摘要 ] 目的:通过检测 EBNA2在 EBV转化的淋巴母细胞的表达分析,为研究 EBV相关淋巴瘤的发生发展提供相应科研数据。方法:采用免疫组织化学法检测 EBNA2基因在 EBV转化淋巴母细胞的细胞蜡块和正常人淋巴细胞的细胞蜡块中的阳性结果。结果: EBNA-2在转化淋巴母细胞的细胞蜡块中呈现棕褐色颗粒的阳性表达,而在正常淋巴细胞细胞蜡块中不表达。结论: EBNA2在 EBV转化的永生化淋巴细胞的细胞蜡块中表达,我们推断 EBNA2在 EB病毒相关恶性淋巴瘤的形成过程中可能起了某些促进作用。
简介:摘要糖尿病是全球主要的健康问题,治疗花费高,有较高的发病率、致残率和死亡率,显著影响患者生活质量。绝大多数糖尿病患者属于2型糖尿病。从既往研究看,减少2型糖尿病并发症的主要策略是加强血糖控制。然而大量证据表明,除了降低非致死性心肌梗死的发生率外,强化(相对于适度)血糖控制对重要的微血管和大血管并发症预后没有显著获益。但是,严格的血糖控制却会增加严重低血糖的风险,并会增加药物种类、副作用和成本等额外负担。此外,来自心血管结局研究的数据表明,使用特定类别的降糖药可大大改善心血管、肾脏和死亡的结果,而这些效应在很大程度上不是由降糖作用带来的。因此,为2型糖尿病患者提供基于循证医学的、以患者为中心的诊疗,需要转变范式并脱离以血糖为中心的糖尿病管理观点。与其优先考虑加强血糖控制,不如将重点放在确保患者获得足够的糖尿病照护,使血糖目标和患者的目标与情况保持一致,最大程度地减少短期和长期并发症,减轻治疗负担以及改善生活质量上。
简介:摘要目的构建大鼠RNAi-腺苷A2a受体(A2aR)慢病毒载体并进行鉴定。方法首先构建3对短发夹RNA(shRNA)-A2aR序列(shRNA-A2aR 1、shRNA-A2aR 2、shRNA-A2aR 3),在shRNA慢病毒载体中分别插入3对双链shRNA oligo,shRNA慢病毒重组质粒构建成功后,将重组质粒、包装载体、穿梭载体共转染293T细胞,从而获得病毒液。实验Ⅰ 采用随机数字表法将大鼠原代心肌细胞分为3组(n=6):空载组(V组)、shRNA-A2aR 1组和shRNA-A2aR 3组,各组分别转染MOI为10的相应病毒液,转染48 h时,Western blot法检测A2aR表达水平,确定干扰效率,以筛选最佳慢病毒载体。实验Ⅱ 采用随机数字表法将大鼠原代心肌细胞分为5组(n=36):空载组(V组)、MOI5组、MOI10组、MOI15组和MOI20组,各组分别转染相应MOI的病毒液(最佳慢病毒载体),于转染24、48和72 h时,采用CCK-8法测定细胞存活率,荧光显微镜下观察细胞活力和细胞死亡情况,Western blot法检测A2aR表达水平,确定干扰效率。结果实验Ⅰ 成功构建了2种shRNA-A2aR慢病毒载体(shRNA-A2aR 1、3)。shRNA-A2aR 3病毒液滴度为3.5×108 TU/ml。与V组和shRNA-A2aR 1组比较,shRNA-A2aR 3组心肌细胞A2aR表达下调(P<0.01),shRNA-A2aR 3慢病毒载体干扰效率73%。实验Ⅱ 选择shRNA-A2aR 3慢病毒载体转染24 h时,各组细胞存活率均>85%;转染48 h时,MOI5组和MOI10组细胞存活率>80%;转染72 h各组细胞存活率<70%。倒置荧光显微镜下可见,MOI5组荧光密度稍低,MOI10组转染48 h及MOI20组转染24 h时,荧光密度较高且细胞状态较好;转染72 h时各组心肌细胞活力明显下降、死亡细胞增加。Western blot显示:MOI10组转染48 h、MOI15组转染48 h、MOI20组转染24和48 h时干扰效率均>70%。结论成功构建了大鼠shRNA-A2aR慢病毒载体,且MOI为10、转染48 h或MOI为20、转染24 h为最佳转染方案。