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101.
目的:探讨白细胞介素(IL)-1β基因多态性与汉族人群生活事件及抑郁障碍的关系。方法:共纳入重性抑郁障碍患者433例作为病例组,并纳入基本情况相匹配的正常对照者421名作为对照组 。以HAMD-17方法分别评定两组受试者抑郁障碍的严重程度,同时以生活事件量表(LES)对病例组近1年的生活事件进行评定。从被试者静脉血中提取基因组DNA,选取IL-1β基因上3个位点:rs13032029 、rs1143623和rs3917368。采用以基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)进行候选基因多态性位点基因分型。运用SPSS22.0统计软件包进行数据分析。结果:在病例组和对照组中,IL-1 β基因rs13032029位点的基因型频率分别为:CC型28.6%和28.5%,CT型47.3%和52.7%,TT型23.8%和18.5%,差异无统计学意义(?字2=4.028,P=0.258)。在病例组和对照组中,rs1143623位点基因型频 率分别为:CC型36.5%和31.1%,GC型45.3%和51.8%,GG型18.0%和16.6%,差异无统计学意义(?字2=4.29,P=0.232)。在病例组和对照组中,rs3917368位点基因型频率分别为:CC型24.5%和25.4%,CT型 47.6%和46.6%,TT型27.3%和27.6%,差异无统计学意义(?字2=0.302,P=0.960)。3个位点不同基因型患者的HAMD总分、各条目之间的差异没有统计学意义。LES总分及生活事件的多元回归分析差异无统 计学意义。结论:未发现IL-1β基因rs13032029、rs1143623和rs3917368基因多态性与汉族人群生活事件和抑郁障碍的发病存在相关性。 相似文献
102.
目的探讨依达拉奉辅助亚低温治疗对重型颅脑创伤(TBI)患者的凝血功能及神经生长因子(NGF)、降钙素基因相关肽(CGRP)的影响。
方法选取沧州市中心医院神经外三科自2018年8月至2019年8月收治的62例重型TBI患者,按随机数字表法分为观察组(31例)和对照组(31例)。对照组患者给予亚低温治疗,观察组患者在亚低温治疗基础上给予依达拉奉辅助治疗14 d。比较2组患者的神经功能缺损评分和疗效,观察治疗前后患者的脑内凝血功能以及血清内NGF、CGRP含量的变化。
结果观察组患者的临床治疗有效率显著高于对照组(P<0.05)。观察组患者采用依达拉奉辅助亚低温治疗后颅内水肿面积显著降低,大脑中动脉平均血流速度明显升高,美国国立卫生研究院卒中量表评分水平显著下降,巴塞尔指数评定量表评分和GCS评分显著增高,差异有统计学意义(P<0.05)。观察组患者采用依达拉奉辅助亚低温治疗后NGF、CGRP水平明显升高,血浆D-二聚体、纤维蛋白原、凝血酶原时间、凝血酶原时间国际标准比值、活化部分凝血活酶时间、凝血酶时间显著下降,抗凝血酶显著上升,差异均有统计学意义(P<0.05)。
结论依达拉奉辅助亚低温治疗重型TBI的临床治疗效果较好,安全性较高,可有效恢复患者的凝血功能,促进NGF、CGRP表达。 相似文献
103.
Solmaz Abdolrahimzadeh Domenica Carmen Piraino Rocco Plateroti Gianluca Scuderi Santi Maria Recupero 《Ophthalmic genetics》2016,37(2):214-216
Background: Neurofibromatosis type 1 (NF-1) is an autsomal dominant disorder which can occasionally result from somatic mosaicism and manifest as segmental forms of the disease.Methods: A 37-year-old woman with ascertained NF-1, based on clinical diagnostic criteria and genetic analysis, was referred for ophthalmological evaluation. Genetic analysis, magnetic resonance imaging (MRI), complete ophthalmological examination, and near infrared reflectance (NIR) images at 815?nm of the retina were obtained.Results: Genetic analysis revealed a non-classified mutational variant of the NF-1 gene identified as NM_000267.3:c2084T?>?C (p.Leu695Pro.T). MRI demonstrated non-symptomatic bilateral optic nerve gliomas. The only cutaneous sign was a subcutaneous neurofibroma of the posterior cervical region. Slit-lamp examination showed bilateral Lisch nodules. NIR images of the retina did not show any choroidal hamartomas.Discussion: We report a rare case of segmental neurofibromatosis with a non-classified mutational variant of the NF-1 gene described in only one previous case in the literature. The patient presented with clinical features of NF-1 localized to the head and neck region, compatible with diagnosis of segmental NF-1. Interestingly, ocular manifestations included bilateral optic nerve gliomas and Lisch nodules, but no choroidal hamartomas. 相似文献
104.
《Biomaterials》2015
In this study, we have shown for the first time the effectiveness of a non-viral gene transfection strategy to re-polarize macrophages from M1 to M2 functional sub-type for the treatment of rheumatoid arthritis (RA). An anti-inflammatory (IL-10) cytokine encoding plasmid DNA was successfully encapsulated into non-condensing alginate based nanoparticles and the surface of the nano-carriers was modified with tuftsin peptide to achieve active macrophage targeting. Enhanced localization of tuftsin-modified alginate nanoparticles was observed in the inflamed paws of arthritic rats upon intraperitoneal administration. Importantly, targeted nanoparticle treatment was successful in reprogramming macrophage phenotype balance as ∼66% of total synovial macrophages from arthritic rats treated with the IL-10 plasmid DNA loaded tuftsin/alginate nanoparticles were in the M2 state compared to ∼9% of macrophages in the M2 state from untreated arthritic rats. Treatment significantly reduced systemic and joint tissue pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) expression and prevented the progression of inflammation and joint damage as revealed by magnetic resonance imaging and histology. Treatment enabled animals to retain their mobility throughout the course of study, whereas untreated animals suffered from impaired mobility. Overall, this study demonstrates that targeted alginate nanoparticles loaded with IL-10 plasmid DNA can efficiently re-polarize macrophages from an M1 to an M2 state, offering a novel treatment paradigm for treatment of chronic inflammatory diseases. 相似文献
105.
Cancers are the most deadly diseases in the world and their incidences continue to increase over time. Particularly, breast cancer in females places 1st rank among other types of cancers in term of cancer cases (23%) and death incidence (14%). Recent findings support the correlation between Ile655Val SNP in the HER2 gene with breast cancer risk. Moreover, the Ile655Val HER2 gene polymorphism could be a predictive factor in a neoadjuvant therapy setting. Precise detection of the Ile655Val HER2 gene SNP in early breast cancer patients will be beneficial in designing the most suitable treatment and in increasing the efficacy of anticancer drugs. Here we develop a rapid and inexpensive method for Ile655Val SNP detection in the HER2 gene based on allele-specific PCR technology. Two forward primers and one common reverse primer were designed to anneal specifically either on the HER2 gene fragment containing the GG genotype or to the HER2 gene fragment containing the AA genotype where one of these primers had been added with poly-GC at 5’ upstream. Moreover, to increase discrimination level, mismatch bases at the SNP site and the 3rd base of each forward primers from 3’end were added. To test the performance of the designed primers in discriminating a polymorphism and its annealing temperature, breast cancer specimen-derived genomic DNA (with GG genotype) and pGEM_HER2/AA (with AA genotype) were used as templates in the PCR reaction. The optimal annealing temperature for SNP detection was at 51.5°C as showed by the appearance of a 150 base pair (bp) band as AA genotype (pGEM_HER2/AA template), 116bp band as GG genotype (genomic DNA template), and both types of bands as AG genotype (mix of pGEM_HER2/AA and genomic DNA template). Allelic types of breast cancer patients were also determined using this optimized method compared to sanger sequencing. The 100% accordance was shown for all types of genotypes in both methods. The allele-specific PCR in this study may have application in determining polymorphisms of the breast cancers-originated Ile655Val HER2 gene. 相似文献
106.
Decorin‐expressing adenovirus decreases collagen synthesis and upregulates MMP expression in keloid fibroblasts and keloid spheroids 下载免费PDF全文
Won Jai Lee Hyo Min Ahn Hyun Roh Youjin Na Il‐Kyu Choi Ju Hee Lee Yong Oock Kim Dae Hyun Lew Chae‐Ok Yun 《Experimental dermatology》2015,24(8):591-597
Decorin is a natural transforming growth factor‐β1 (TGF‐β1) antagonist. Reduced decorin synthesis is associated with dermal scarring, and increased decorin expression appears to reduce scar tissue formation. To investigate the therapeutic potential of decorin for keloids, human dermal fibroblasts (HDFs) and keloid‐derived fibroblasts (KFs) were transduced with decorin‐expressing adenovirus (dE1‐RGD/GFP/DCN), and we examined the therapeutic potential of decorin‐expressing Ad for treating pathologic skin fibrosis. Decorin expression was examined by immunofluorescence assay on keloid tissues. HDFs and KFs were transduced with dE1‐RGD/GFP/DCN or control virus, and protein levels of decorin, epidermal growth factor receptor (EGFR) and secreted TGF‐β1 were assessed by Western blotting and ELISA. And type I and III collagen, and matrix metalloproteinase‐1 (MMP‐1) and matrix metalloproteinase‐3 (MMP‐3) mRNA levels were measured by real‐time RT‐PCR. Additionally, we immunohistochemically investigated the expression levels of the major extracellular matrix (ECM) proteins in keloid spheroids transduced with dE1‐RGD/GFP/DCN. Lower decorin expression was observed in the keloid region compared to adjacent normal tissues. After treatment with dE1‐RGD/GFP/DCN, secreted TGF‐β1 and EGFR protein expressions were decreased in TGF‐β1‐treated HDFs and KFs. Also, type I and III collagen mRNA levels were decreased, and the expression of MMP‐1 and MMP‐3 mRNA was strongly upregulated. In addition, the expression of type I and III collagen, fibronectin and elastin was significantly reduced in dE1‐RGD/GFP/DCN‐transduced keloid spheroids. These results support the utility of decorin‐expressing adenovirus to reduce collagen synthesis in KFs and keloid spheroid, which may be highly beneficial in treating keloids. 相似文献
107.
Hyperbranched poly(amidoamine) (HPAMAM), structurally analogous to polyamidoamine dendrimer (PAMAM) dendrimers, has been suggested to be an effective carrier for gene delivery. In the present study, glutamic acid-modified hPAMAM was developed as a novel non-viral gene carrier for the first time. The hPAMAM was synthesized by using a modified one-pot method. DNA was found to be bound to hPAMAM at different weight ratios (WhPAMAM/WDNA). The resulting HPAMAM–Glu20 was able to efficiently protect the encapsulated-DNA against degradation for over 2?h. In addition to low cytotoxicity, the transfection efficiency of hPAMAM–Glu20 represented much higher (p?<?0.05) than that of Lipofectamine 2000 in both MCF7 and MDA-MB231 cells. Cellular uptake of the hPAMAM–Glu20 in MDA-MB231 cells, 173.56?±?1.37%, was significantly higher than that of MCF7 cells, 65.00?±?1.73% (p?<?0.05). The results indicated that hPAMAM–Glu20-mediated gene delivery to breast cancer cells is a feasible and effective strategy that may provide a new therapeutic avenue as a non-viral gene delivery carrier. In addition, it was found that hPAMAM–glutamic amino acid (Glu)-based gene delivery is an economical, effective and biocompatible method. 相似文献
108.
109.
目的:分析CYP2C19*3基因多态性与癫痫患者奥卡西平(oxcarbazepine,OXC)活性代谢产物10,11-二氢-10-羟基卡马西平(monohydroxycarbazepine,MHD)血药浓度的相关性。方法:纳入120例OXC单药治疗1个月以上且症状控制良好的癫痫患者,采集清晨服药前空腹血,采用高效液相色谱法测定MHD稳态谷浓度。通过PCR和sanger测序判定患者CYP2C19*3基因型。结果:120例癫痫患者快代谢患者64例,MHD血浆浓度为(18.17±7.34)μg·mL-1;中代谢型患者36例,MHD血浆浓度为(19.31±9.17)μg·mL-1;慢代谢型患者20例,MHD血浆浓度为(25.79±7.51)μg·mL-1,3种基因型的MHD浓度有显著性差异(F=7.077,P=0.0013)。多因素分析显示,日剂量作为影响血药浓度的重要指标呈现出显著相关性(P<0.05)。结论:CYP2C19*3基因多态性影响MHD血药浓度,并且日剂量越高,MHD血药浓度越大,两者成显著正相关,临床应进行血药浓度监测。 相似文献
110.