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1.
目的观察谷氨酰胺肠内营养联合低分子肝素对老年慢性阻塞性肺疾病(COPD)并发重症肺部感染患者炎症与氧化应激反应的影响分析。方法将安阳地区医院2016年01月至2018年12月收治的COPD并发重症感染患者150例,根据患者入院治疗顺序分成对照组与实验组各75例,其中对照组患者采取常规治疗基础上联合低分子肝素治疗,实验组采取常规治疗上谷氨酰胺肠内营养联合低分子肝素治疗。对照两组患者治疗前、后机体内免疫功能指标[免疫球蛋白G(IgG)、免疫球蛋白M (IgM)、免疫球蛋白A (IgA)、CD4/CD8]、炎性反应指标[白细胞介素-6 (IL-6)、肿瘤坏死因子-α(TNF-α);使用免疫比浊发检测C-反应蛋白(CRP)]、氧化应激反应指标[超氧歧化酶(SOD)、血清丙二醛(MDA)]、肺功能指标[肺活量(VC)、用力肺活量(FVC)、第1秒用力呼气容积(FEV_1)、FEV_1/FVC]及临床治疗效果。结果治疗后两组患者免疫功能指标均明显提高,实验组各项免疫功能指标高于对照组;治疗后两组患者炎性反应指标均明显下降,实验组患者各项炎性反应指标低于对照组;治疗后两组患者氧化应激反应指标均明显改善,实验组患者SOD反应指标高于对照组,MDA指标低于对照组;治疗后两组患者肺功能相关指标均明显改善,实验组优于对照组;实验组患者临床总有效率为97.33%,对照组为82.67%(P<0.01)。结论采取谷氨酰胺肠内营养联合肝素治疗COPD并发重症肺部感染患者,可明显提高患者机体免疫功能指标,减少机体内炎性反应指标,调节机体氧化应激指标,进而改善肺功能指标,提高患者临床治疗有效率,效果理想。  相似文献   
2.
Biallelic rare variants in NARS2 that encode the mitochondrial asparaginyl-tRNA synthetase are associated with a wide spectrum of clinical phenotypes ranging from severe neurodegenerative disorders to isolated mitochondrial myopathy or deafness. To date, only a small number of patients with NARS2 variants have been reported, and possible genotype-phenotype correlations are still lacking. Here, we present three siblings who had an early-onset hearing loss, while one developed severe symptoms in adulthood associated with early intellectual impairment, refractory seizures, moderate axonal sensorimotor neuropathy, and atypical psychiatric symptoms. Biochemical analysis revealed impairment of the activity and assembly of the respiratory chain complexes in this patient's muscle and fibroblasts. Whole Exome Sequencing allowed identification of a heterozygous variant NM_024678.5(NARS2):c.822G > C (p.Gln274His) that is known to be pathogenic and to affect splicing of the NARS2 gene, but was unable to detect a second variant in this gene. Coverage analysis and Sanger sequencing led to identification of a novel intronic deletion NM_024678.5(NARS2):c.922-21_922-19del in the three siblings in trans with the c.822G > C. Functional analysis by RT-PCR showed that this deletion was causing aberrant splicing and led to exon 9 skipping in NARS2 mRNA in patient fibroblasts. Our work expands the phenotype and genotype spectrum of NARS2-related disorders. We provide evidence of the pathogenic effect of a novel intronic deletion in the NARS2 gene and report on additional adult patients with a large intrafamilial variability associated with splice variants in this gene. More specifically, we detail the phenotype of the oldest living patient to date with NARS2 variants and, for the first time, we report the psychiatric symptoms associated with this gene. Our work confirms the complexity of genotype-phenotype correlation in patients with pathogenic NARS2 variants.  相似文献   
3.
Glutaric Aciduria type I (GA-I) is caused by mutations in the GCDH gene. Its deficiency results in accumulation of the key metabolites glutaric acid (GA) and 3-hydroxyglutaric acid (3-OHGA) in body tissues and fluids. Present knowledge on the neuropathogenesis of GA-I suggests that GA and 3-OHGA have toxic properties on the developing brain.We analyzed morphological and biochemical features of 3D brain cell aggregates issued from Gcdh?/? mice at two different developmental stages, day-in-vitro (DIV) 8 and 14, corresponding to the neonatal period and early childhood. We also induced a metabolic stress by exposing the aggregates to 10 mM l-lysine (Lys).Significant amounts of GA and 3-OHGA were detected in Gcdh?/? aggregates and their culture media. Ammonium was significantly increased in culture media of Gcdh?/? aggregates at the early developmental stage. Concentrations of GA, 3-OHGA and ammonium increased significantly after exposure to Lys. Gcdh?/? aggregates manifested morphological alterations of all brain cell types at DIV 8 while at DIV 14 they were only visible after exposure to Lys. Several chemokine levels were significantly decreased in culture media of Gcdh?/? aggregates at DIV 14 and after exposure to Lys at DIV 8.This new in vitro model for brain damage in GA-I mimics well in vivo conditions. As seen previously in WT aggregates exposed to 3-OHGA, we confirmed a significant ammonium production by immature Gcdh?/? brain cells. We described for the first time a decrease of chemokines in Gcdh?/? culture media which might contribute to brain cell injury in GA-I.  相似文献   
4.
Seasonal and pandemic influenza infections remain a serious public health concern. Many health authorities recommend annual vaccination as the most effective way to control influenza infection. Accordingly, regulatory guidelines ask vaccine manufacturers to determine vaccine potency at the time of release and throughout shelf-life to ensure vaccine quality. The potency of inactivated influenza vaccine is related to the quantity of hemagglutinin (HA). Since 1970s, single radial immunodiffusion (SRID) assay has been standardly used for the quantitation of HA in influenza vaccine. However, SRID is labor-intensive, inaccurate, and requires standard reference reagents that should be updated annually. Therefore, there have been extensive efforts to develop alternative potency assays. In this study, we developed and tested a new HA quantitative enzyme-linked immunosorbent assay (ELISA) using a universal monoclonal antibody that can bind to HAs from various subtypes in group 1 influenza A virus (IAV). We analyzed the conserved stalk domain of HA via a library approach to design a consensus HA antigen for group 1 IAV. The antigens were expressed as a soluble form in E. coli and were purified by Ni-affinity chromatography. When tested with variety of HAs from IAVs or influenza B viruses (IBVs), the mAbs exhibited specific binding to group 1 HAs, with potential exception to H9 subtype. Among various conditions of pH, urea, and reducing agents, pretreatment of HA at low pH exposing the conserved stalk domain was crucially important for optimal ELISA performance. Calibration curves for various HAs were generated to determine accuracy, specificity, sensitivity, and linear dynamic range. The ELISA method shows high sensitivity and accuracy compared with the SRID assay. The HA group specific universal mAbs against the consensus stalk domain of HA are conducive to establishing an ELISA-based standard procedure for the quantitation of HA antigens for annual vaccination against influenza infection.  相似文献   
5.
l -glutamine was approved by the U.S. Food and Drug Administration (FDA) for sickle cell disease (SCD) in 2017. A vaso-occlusive crisis (VOC) occurs in persons with SCD and is associated with acute pain episodes. This systematic review summarizes the evidence for l -glutamine in the prevention of VOC and associated pain in patients with SCD. Medline, Embase, and International Pharmaceutical Abstracts were searched for records reporting on l -glutamine use in persons with SCD. Eligibility criteria identified primary reports of investigations conducted in humans who were administered l -glutamine, reported on outcomes related to VOC or associated pain, published in English, and were available as full text. All relevant efficacy, safety, participant demographic data, and study method characteristics were extracted and documented. Risk-of-bias assessments were conducted using the Risk of Bias in Non-Randomized Studies-of Interventions (ROBINS-I) tool and the revised Cochrane risk-of-bias tool for randomized studies. Three studies assessing the effect of exogenous l -glutamine administration in patients with SCD met eligibility criteria: one prospective nonrandomized controlled study and two prospective randomized controlled trials. Rate of VOC and related hospitalizations were reduced in patients receiving l -glutamine, although some conflicting results were noted between studies. l -glutamine was generally well tolerated. Limitations of one or more of the eligible studies included small sample size, nonblinding, and study groups that differed at baseline. l -glutamine has limited high-quality evidence supporting its use. Although l -glutamine is FDA approved for the prevention of frequent episodes of VOC pain, only one randomized controlled trial has strong evidence to support this indication. Based on the results of a systematic review, l -glutamine may be considered for patients unable to receive hydroxyurea or in addition to hydroxyurea for reduction in VOC and associated pain.  相似文献   
6.
刘静  孙蓉 《中草药》2020,51(14):3708-3716
目的通过构建蛋氨酸-胆碱缺乏(MCD)饮食诱导的小鼠非酒精性脂肪性肝炎(NASH)模型,研究小柴胡汤对NASH模型小鼠的保护作用。方法选择C57BL/6小鼠为研究对象,将其随机分为对照组、模型组、小柴胡汤(高、中、低剂量)组、易善复组和强肝胶囊组。通过饲喂MCD饲料建立NASH模型,造模同时按分组给予不同药物进行干预;实验过程中记录小鼠体质量、日摄食量、日饮水量变化,实验结束对肝组织进行HE染色观察病理变化,检测血清生化指标丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、白细胞介素6(IL-6)和肿瘤坏死因子-α(TNF-α)的水平变化,检测肝组织中TC、TG的水平变化,利用q RT-PCR技术检测肝组织脂肪酸合成酶(FAS)和固醇调节元件结合蛋白1c(SREBP-1c)的表达水平。结果小鼠体质量、日摄食量、日饮水量及肝脏系数等数据显示MCD饮食诱导的模型组小鼠会出现体质量降低、摄入量减少及肝脏湿质量下降的特点,而小柴胡汤给药组小鼠体质量、摄入量及肝脏系数较模型组小鼠显著升高;HE染色结果显示小柴胡汤可明显减轻肝组织脂肪变性和炎症程度,改善肝细胞的形态和结构;生化指标检测结果显示小柴胡汤能显著降低NASH模型小鼠血清及肝组织TG、TC水平,升高血清中HDL-C水平,降低血清中AST、ALT、IL-6、TNF-α水平;q RT-PCR结果显示模型组小鼠肝组织FAS和SREBP-1c的基因表达水平明显升高,小柴胡汤可显著降低FAS和SREBP-1c的基因表达水平。结论小柴胡汤对MCD饮食诱导的NASH模型小鼠有明显保护作用,其机制可能通过调控抑制脂肪酸合成基因(FAS、SREBP-1c)的表达,减少脂肪堆积,实现调脂作用,并通过抑制炎症因子的表达改善肝组织的损伤。  相似文献   
7.
目的 研究复方谷氨酰胺联合柳氮磺吡啶治疗溃疡性结肠炎的临床疗效。方法 选择2017年1月-2019年1月榆林市星元医院的120例溃疡性结肠炎患者作为研究对象,采用抽签法随机分为对照组和观察组,每组各60例。对照组患者口服柳氮磺吡啶肠溶片,6片/次,3次/d。观察组患者在对照组的基础上口服复方谷氨酰胺肠溶胶囊,3粒/次,3次/d。两组均治疗4周。观察两组患者的临床疗效,比较两组治疗前后的相关症状、评分情况,以及炎性因子水平。结果 治疗后,观察组的总有效率为91.67%,明显高于对照组的71.67%(P<0.05)。治疗后,观察组的黏液脓血便消失时间为(10.13±1.27)d,明显短于对照组的(19.73±2.45)d(P<0.05)。两组治疗后的疾病活动指数和腹痛程度评分均明显降低(P<0.05),且观察组明显更低(P<0.05)。两组治疗后的血清白细胞介素(IL)-6、肿瘤坏死因子-α(TNF-α)、IL-8、超敏C反应蛋白(hs-CRP)水平均明显降低(P<0.05),且观察组明显更低(P<0.05)。结论 复方谷氨酰胺联合柳氮磺吡啶对溃疡性结肠炎的疗效较佳,能明显减轻腹痛程度,改善炎症因子水平,降低疾病活动指数。  相似文献   
8.
《Molecular therapy》2020,28(11):2458-2472
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9.
ObjectiveTo investigate the molecular cause(s) underlying a severe form of infantile-onset parkinsonism and characterize functionally the identified variants.MethodsA trio-based whole exome sequencing (WES) approach was used to identify the candidate variants underlying the disorder. In silico modeling, and in vitro and in vivo studies were performed to explore the impact of these variants on protein function and relevant cellular processes.ResultsWES analysis identified biallelic variants in WARS2, encoding the mitochondrial tryptophanyl tRNA synthetase (mtTrpRS), a gene whose mutations have recently been associated with multiple neurological phenotypes, including childhood-onset, levodopa-responsive or unresponsive parkinsonism in a few patients. A substantial reduction of mtTrpRS levels in mitochondria and reduced OXPHOS function was demonstrated, supporting their pathogenicity. Based on the infantile-onset and severity of the phenotype, additional variants were considered as possible genetic modifiers. Functional assessment of a selected panel of candidates pointed to a de novo missense mutation in CHRNA6, encoding the α6 subunit of neuronal nicotinic receptors, which are involved in the cholinergic modulation of dopamine release in the striatum, as a second event likely contributing to the phenotype. In silico, in vitro (Xenopus oocytes and GH4C1 cells) and in vivo (C. elegans) analyses demonstrated the disruptive effects of the mutation on acetylcholine receptor structure and function.ConclusionOur findings consolidate the association between biallelic WARS2 mutations and movement disorders, and suggest CHRNA6 as a genetic modifier of the phenotype.  相似文献   
10.
《Molecular therapy》2020,28(7):1717-1730
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