cholesterol

胆固醇
  • 文章类型: Journal Article
    该研究旨在评估不同水平饲喂保护的the油对公羊精子质量的影响。该研究使用了15只本地公羊,年龄约为10-12个月,初始重量为19.99±3.97kg。摄食率为每天体重的4%。每天喂3次,特别是在早上(08.00WIB),下午(12.00WIB)和晚上(16.00WIB)。随意提供水。该研究使用3个处理和5组作为重复。处理使用具有不同水平的受保护的the油的浓缩物:P0(0%受保护的the油(对照)),P1(4%受保护的the油),和P2(8%受保护的the油)。测量的变量是营养消耗,血胆固醇水平,阴囊周长,和精子质量。在实验饮食结束时测量血液胆固醇和阴囊围。在实验饮食之前和结束时收集和分析精液样品。获得的数据使用方差分析,进一步测试使用邓肯的测试显着差异。结果表明,干物质的消耗没有显着差异,粗蛋白,粗纤维,阴囊周长,volume,颜色,精液的pH值,精子浓度,活的百分比,异常百分比,质膜,精子的顶体完整性。有显著(p<0.05)产生更高的消耗的油酸和棕榈酸在8%的保护与4%处理相比,含有4%和8%受保护的aggot油的处理显著(p<0.05)增加了月桂酸和肉豆蔻酸的消耗,血胆固醇水平,和精子活力比对照。结果表明,在公羊日粮中含8%以上的虫草油对提高公羊精子的微观质量有积极作用。即精子活力增加。
    The study aimed to to evaluate the effect of feeding protected maggot oil at different levels on the ram sperm quality. The study used 15 local rams with an age of approximately 10-12 months and an initial weight of 19.99 ± 3.97 kg. The feeding rate was 4% of body weight per day. Feed was given 3 times a day, specifically in the morning (08.00 WIB), afternoon (12.00 WIB) and evening (16.00 WIB). Water was provided ad libitum. This study used 3 treatments and 5 groups as replicates. The treatments used concentrates with different levels of protected maggot oil: P0(0% protected maggot oil (control)), P1(4% protected maggot oil), and P2(8% protected maggot oil). The variables measured were nutrient consumption, blood cholesterol levels, scrotal circumference, and sperm quality. Blood cholesterol and scrotal circumference measured at the end of the experimental diet. Semen samples were collected and analysed before and at the end of the experimental diet. The data obtained were analysed using ANOVA, with further testing using Duncan\'s test for significant differences. The results showed that there were no significant differences in the consumption of dry matter, crude protein, crude fiber, scrotal circumference, volume, colour, pH of semen, sperm concentration, live percentage, abnormal percentage, plasma membrane, and acrosome integrity of spermatozoa. There were significantly (p < 0.05) produced higher consumption of oleic and palmitic acids in 8% protected maggot oil compared to 4% treatments, the treatments containing 4% and 8% protected maggot oil produced significantly (p < 0.05) higher consumption of lauric and myristic acids, blood cholesterol levels, and sperm motility than the control. The result indicates that protected maggot oil up to 8% in the ram diet have positive effect on improving the microscopic quality of ram sperm, i.e. increased sperm motility.
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  • 文章类型: Journal Article
    胆固醇是中枢神经系统和组织的重要组成部分,了解它的空间分布对生物学至关重要,病理生理学,和诊断。然而,使用基质辅助激光解吸/电离质谱成像(MALDI-MSI)对胆固醇进行直接成像仍然具有挑战性且耗时,因为难以电离甾醇分子。为了解决这个问题,建立了MALDI-MSI方法,用于直接和快速分析阿尔茨海默病(AD)中胆固醇的空间分布,通过MALDI-MSI不同的癌组织和器官。这种优异的成像性能取决于影响MALDI-MSI成像的各种条件的研究和系统优化。在这种情况下,我们报告了胆固醇在AD小鼠大脑和不同肿瘤组织和器官的特定结构中的分布和水平。根据结果,AD小鼠小脑中的胆固醇含量,尤其是在侧柏中,显著高于野生型(WT)模型。此外,我们成功地可视化了胆固醇在其他器官中的分布,比如心脏,肝脏,脾,脾肾,胰腺,以及使用MALDI-MSI的肿瘤组织实质和间质。值得注意的是,系统研究了胆固醇MS/MS烃碎片的归属。我们提出的优化策略和建立的MALDI-MSI方法可以很容易地推广到不同的动物组织或活样品,从而促进MALDI-MSI在临床上的应用潜力,医学和生物学研究。
    Cholesterol is a vital component of the central nervous system and tissues, and understanding its spatial distribution is crucial for biology, pathophysiology, and diagnostics. However, direct imaging of cholesterol using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) remains challenging and time-consuming due to the difficulty in ionizing the sterol molecule. To tackle this issue, a MALDI-MSI method is established for direct and rapid analysis of the spatial distribution of cholesterol in Alzheimer\'s disease (AD), different cancer tissues and organs via MALDI-MSI. This excellent imaging performance depends on the study and systemic optimization of various conditions that affect the imaging of MALDI-MSI. In this case, we report the distribution and levels of cholesterol across specific structures of the AD mouse brain and different tumor tissue and organs. According to the results, the content of cholesterol in the AD mouse cerebellum, especially in the arborvitae, was significantly higher than that in the wild type (WT) model. Furthermore, we successfully visualize the distribution of cholesterol in other organs, such as the heart, liver, spleen, kidney, pancreas, as well as tumor tissues parenchyma and interstitium using MALDI-MSI. Notably, the attribution of cholesterol MS/MS hydrocarbon fragments was systematically investigated. Our presented optimization strategy and established MALDI-MSI method can be easily generalized for different animal tissues or live samples, thereby facilitating the potential for applications of MALDI-MSI in clinical, medical and biological research.
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  • 文章类型: Journal Article
    目的:口服避孕是成人和青少年中最流行的避孕方法之一。然而,口服避孕药对青少年血脂的影响尚未得到充分研究.
    方法:在2015年至2018年期间,在基于前瞻性人群的早期血管老化-蒂罗尔研究的14至19岁女性参与者中,测量了血脂谱并评估了避孕药具的使用,平均间隔22个月两次。
    结果:对于此分析,我们获得了828名中位年龄为17.0岁的年轻女性的数据.其中,317(38%)使用口服避孕药(OC)。OC使用者的收缩压和舒张压略高,并且随着时间的推移变化更大,并且与非使用者相比更可能使用香烟。总胆固醇(179.6vs.162.4mg/dL),低密度脂蛋白胆固醇(106.4vs.94.6mg/dL),和甘油三酯(104.0vs.在线性回归模型中进行多变量调整后,OC使用者的67.0mg/dL)明显更高。两组之间的高密度脂蛋白-胆固醇没有差异。在558名女性中,随访数据可用。那些开始使用OC的人在基线和随访之间的低密度脂蛋白胆固醇平均高15.4mg/dL,甘油三酯水平变化高36.2mg/dL。OC使用的持续时间与脂质水平和变化没有显着关联。
    结论:我们在一个大的健康青少年队列中显示,随着时间的推移,OC使用与血脂和血脂轨迹之间存在独立的关联。这些变化与考虑其他血脂异常或其他心血管危险因素的青少年尤其相关。
    OBJECTIVE: Oral contraception is one of the most popular contraceptive methods both in adults and adolescents. However, the effects of oral contraception on lipids in adolescents are not well studied.
    METHODS: Lipid profiles were measured and contraceptive use was assessed in 14- to 19-year-old female participants of the prospective population-based Early Vascular Ageing-Tyrol Study between 2015 and 2018, twice on average 22 months apart.
    RESULTS: For this analysis, data from 828 young women with a median age of 17.0 years were available. Of them, 317 (38%) used oral contraceptives (OCs). OC users had a slightly higher systolic and diastolic blood pressure and larger changes over time and were more likely to use cigarettes than nonusers. Total cholesterol (179.6 vs. 162.4 mg/dL), low-density lipoprotein-cholesterol (106.4 vs. 94.6 mg/dL), and triglycerides (104.0 vs. 67.0 mg/dL) were significantly higher in OC users after multivariable adjustment in linear regression models. No difference in high-density lipoprotein-cholesterol between the two groups was found. In 558 females, follow-up data were available. Those who initiated OC use had on average 15.4 mg/dL higher low-density lipoprotein-cholesterol and 36.2 mg/dL higher triglyceride level changes between baseline and follow-up than never users. Duration of OC use did not show a significant association with lipid levels and changes.
    CONCLUSIONS: We showed an independent association between OC use and blood lipids as well as lipid trajectories over time in a large cohort of healthy adolescents. These changes are especially relevant to consider in adolescents with other risk factors for dyslipidemia or other cardiovascular risk factors.
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  • 文章类型: Journal Article
    肥胖是妊娠并发症发生的重要危险因素。我们调查了孕前超重和肥胖对妊娠期母体脂质组和新生儿特征的影响。这项研究涵盖了131名孕妇,99,孕前体重指数(BMI)<25kg/m2,32,BMI≥25kg/m2。产妇血脂状况参数,在每三个月测定胆固醇合成和吸收以及鞘脂的血浆标志物。新生儿身高数据,评估体重和APGAR评分.结果显示,在孕前BMI升高的参与者中,妊娠和分娩并发症的患病率更高(p<0.05)。总胆固醇水平,HDL-胆固醇(p<0.05)和LDL-胆固醇(p<0.01)显著降低,孕前BMI增加的妇女的甘油三酯浓度较高(p<0.05)。较低浓度的胆固醇合成标记,地莫甾醇,在妊娠中期(p<0.01)和胆固醇吸收标记,菜油甾醇,在每个三个月中(分别为p<0.01,p<0.05,p<0.01)也在该组中发现。孕前体重健康的母亲组中,母亲胆固醇合成指标与新生儿APGAR评分呈正相关,而超重/肥胖组呈负相关。我们的结果表明,母体脂质组的妊娠适应取决于她的孕前营养状况,这种变化可能会影响新生儿结局。
    Obesity is an important risk factor for the development of pregnancy complications. We investigated the effects of pregestational overweight and obesity on maternal lipidome during pregnancy and on newborns\' characteristics. The study encompassed 131 pregnant women, 99 with pre-pregnancy body mass index (BMI) < 25 kg/m2 and 32 with BMI ≥ 25 kg/m2. Maternal lipid status parameters, plasma markers of cholesterol synthesis and absorption and sphingolipids were determined in each trimester. Data on neonatal height, weight and APGAR scores were assessed. The results showed a higher prevalence (p < 0.05) of pregnancy and childbirth complications among the participants with elevated pregestational BMI. Levels of total cholesterol, HDL-cholesterol (p < 0.05) and LDL-cholesterol (p < 0.01) were significantly lower, and concentrations of triglycerides were higher (p < 0.05) in women with increased pre-gestational BMI. Lower concentrations of the cholesterol synthesis marker, desmosterol, in the 2nd trimester (p < 0.01) and the cholesterol absorption marker, campesterol, in each trimester (p < 0.01, p < 0.05, p < 0.01, respectively) were also found in this group. Markers of maternal cholesterol synthesis were in positive correlation with neonatal APGAR scores in the group of mothers with healthy pre-pregnancy weight but in negative correlation in the overweight/obese group. Our results indicate that gestational adaptations of maternal lipidome depend on her pregestational nutritional status and that such changes may affect neonatal outcomes.
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  • 文章类型: Journal Article
    过氧化物酶体增殖物激活受体(PPARs)可能在阿尔茨海默病(AD)和其他几种神经/神经精神疾病的发病机制中发挥重要作用。AD导致氧化还原状态的进行性改变,离子稳态,脂质,和蛋白质代谢。分子过程的显著改变和几个信号通路的功能导致突触和神经元细胞的变性和死亡,导致最严重的痴呆.过氧化物酶体增殖物激活受体α(PPAR-α)是受AD影响的过程之一;它调节与胆固醇代谢相关的基因的转录,脂肪酸,其他脂质和神经传递,线粒体生物发生,和功能。PPAR-α参与胆固醇向线粒体的转运,神经类固醇生物合成的底物。PPAR-α编码酶,如磺基转移酶,负责神经类固醇硫酸化。PPAR-α与胆固醇/神经类固醇之间的关系可能对神经变性/神经保护过程的过程和进展具有重大影响。不幸的是,尽管经过多年的深入研究,AD的发病机制尚不清楚,AD和其他神经退行性疾病的治疗是有症状的,今天提出了一个重要的目标和挑战。这篇综述介绍了AD治疗方法的最新进展。在AD和神经精神疾病中靶向PPAR-α及其与胆固醇和神经类固醇的关系。
    Peroxisome proliferator-activated receptors (PPARs) may play an important role in the pathomechanism/pathogenesis of Alzheimer\'s disease (AD) and several other neurological/neuropsychiatric disorders. AD leads to progressive alterations in the redox state, ion homeostasis, lipids, and protein metabolism. Significant alterations in molecular processes and the functioning of several signaling pathways result in the degeneration and death of synapses and neuronal cells, leading to the most severe dementia. Peroxisome proliferator-activated receptor alpha (PPAR-α) is among the processes affected by AD; it regulates the transcription of genes related to the metabolism of cholesterol, fatty acids, other lipids and neurotransmission, mitochondria biogenesis, and function. PPAR-α is involved in the cholesterol transport to mitochondria, the substrate for neurosteroid biosynthesis. PPAR-α-coding enzymes, such as sulfotransferases, which are responsible for neurosteroid sulfation. The relation between PPAR-α and cholesterol/neurosteroids may have a significant impact on the course and progression of neurodegeneration/neuroprotection processes. Unfortunately, despite many years of intensive studies, the pathogenesis of AD is unknown and therapy for AD and other neurodegenerative diseases is symptomatic, presenting a significant goal and challenge today. This review presents recent achievements in therapeutic approaches for AD, which are targeting PPAR-α and its relation to cholesterol and neurosteroids in AD and neuropsychiatric disorders.
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  • 文章类型: Systematic Review
    (1)背景:哮喘是一种在成人和儿童中发现的综合征,以气道炎症引起的气流阻塞为特征。近年来,越来越多的研究发现,脂质代谢影响哮喘的发展和症状学。脂质代谢在加重的发生和减轻肺部炎症中起重要作用。我们的研究旨在确定诊断为哮喘的患者与血脂之间的任何类型的关联,包括HDL-胆固醇,LDL-胆固醇,总胆固醇,和成人的甘油三酯。(2)方法:找到供我们评论的文章,我们搜索了两个平台:PubMed和GoogleScholar。共分析了来自两个平台的309篇文章。最后,从最初的已识别文章库中选择了12篇论文。(3)结果:甘油三酯之间呈正相关,总胆固醇,低密度脂蛋白胆固醇(LDL-胆固醇),哮喘已在多项研究中得到证实。此外,在特应性患者中,2型炎症的生物标志物与HDL和血清甘油三酯之间似乎存在关联.关于哮喘患者的营养,对疾病发展的最大影响似乎是水果和蔬菜的消费。一些研究表明,以素食为主的饮食与更好地控制疾病和减少促炎细胞因子的数量有关。(4)结论:研究表明总胆固醇与胆固醇呈正相关,甘油三酯,LDL-胆固醇水平与哮喘呈负相关,HDL-胆固醇与哮喘呈负相关。增加的胆固醇值将导致促炎过程的刺激和参与这些过程的细胞因子的分泌。哮喘患者最成功的饮食似乎是那些食用水果的饮食,蔬菜,高纤维食物增加是因为所有这些食物都富含维生素,抗氧化剂,和矿物。
    (1) Background: Asthma is a syndrome found in both adults and children, characterized by airflow obstruction caused by the inflammation of the airways. In recent years, an increasing number of studies have found that lipid metabolism influences both the development and symptomatology of asthma. Lipid metabolism plays an important role both in the occurrence of exacerbations and in the reduction of lung inflammation. Our study aimed to identify any type of association between patients diagnosed with asthma and their serum lipids, including HDL-cholesterol, LDL-cholesterol, total cholesterol, and triglycerides in adults. (2) Methods: To find articles for our review, we searched two platforms: PubMed and Google Scholar. A total of 309 articles from two platforms were analyzed. Finally, 12 papers were selected from the initial pool of identified articles. (3) Results: The positive correlation between triglycerides, total cholesterol, low-density lipoprotein-cholesterol (LDL-cholesterol), and asthma has been demonstrated in several studies. Moreover, it appears that there is an association between biomarkers of type 2 inflammation and HDL and serum triglycerides in people with atopic status. Regarding the nutrition of asthmatic patients, the greatest impact on the development of the disease seems to be the consumption of fruit and vegetables. Several studies show that a predominantly vegan diet is associated with better control of the disease and a decrease in the number of pro-inflammatory cytokines. (4) Conclusions: Studies show a positive correlation between total cholesterol, triglyceride, and LDL-cholesterol levels and asthma and a negative correlation between HDL-cholesterol and asthma. Increased cholesterol values would lead to the stimulation of pro-inflammatory processes and the secretion of cytokines involved in these processes. The most successful diets for asthma patients seem to be those in which the consumption of fruit, vegetables, and high-fiber foods is increased because all of these food groups are rich in vitamins, antioxidants, and minerals.
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  • 文章类型: Journal Article
    (1)背景:最近,学术研究表明,果胶寡糖(POSs)的降胆固醇作用与肠道菌群相关。然而,POS对胆固醇代谢的机制是有限的,肠道菌群的观察缺乏综合分析。(2)目的和方法:通过对肠道菌群的综合分析,揭示POS对胆固醇代谢的调控机制。通过体外肠道菌群发酵,使用IlluminaMiSeq测序和非靶向代谢组学研究了添加POS后肠道菌群结构和代谢物组成的变化.(3)结果:POS对粪便肠道菌群的组成有积极的调节作用。POS增加了胆固醇相关细菌群的丰度拟杆菌,双歧杆菌和乳杆菌,虽然它减少了条件致病性大肠杆菌和肠球菌,表现出良好的益生元活性。POS改变了肠道菌群发酵代谢产物的组成(P24),在非靶向代谢组学分析中引起221种发酵代谢物的显著变化,并促进短链脂肪酸的产生。四种类型的胆固醇代谢相关代谢物的丰度(腺苷一磷酸,环磷酸腺苷,P24组的鸟苷和丁酸酯)明显高于未添加POS的对照组。(4)结论:上述结果可能解释了POS的低胆固醇血症作用和P24对胆固醇流出的促进作用。这些发现表明,柑橘POS对胆固醇代谢的潜在调节机制受到胆固醇相关肠道菌群和特定代谢产物的调节。
    (1) Background: Recently, academic studies are demonstrating that the cholesterol-lowering effects of pectin oligosaccharides (POSs) are correlated to intestinal flora. However, the mechanisms of POS on cholesterol metabolisms are limited, and the observations of intestinal flora are lacking integrative analyses. (2) Aim and methods: To reveal the regulatory mechanisms of POS on cholesterol metabolism via an integrative analysis of the gut microbiota, the changes in gut microbiota structure and metabolite composition after POS addition were investigated using Illumina MiSeq sequencing and non-targeted metabolomics through in vitro gut microbiota fermentation. (3) Results: The composition of fecal gut flora was adjusted positively by POS. POS increased the abundances of the cholesterol-related bacterial groups Bacteroidetes, Bifidobacterium and Lactobacillus, while it decreased conditional pathogenic Escherichia coli and Enterococcus, showing good prebiotic activities. POS changed the composition of gut microbiota fermentation metabolites (P24), causing significant changes in 221 species of fermentation metabolites in a non-targeted metabolomics analysis and promoting the production of short-chain fatty acids. The abundances of four types of cholesterol metabolism-related metabolites (adenosine monophosphate, cyclic adenosine monophosphate, guanosine and butyrate) were significantly higher in the P24 group than those in the control group without POS addition. (4) Conclusion: The abovementioned results may explain the hypocholesterolemic effects of POS and promotion effects on cholesterol efflux of P24. These findings indicated that the potential regulatory mechanisms of citrus POS on cholesterol metabolism are modulated by cholesterol-related gut microbiota and specific metabolites.
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  • 文章类型: Journal Article
    年龄相关性黄斑变性(AMD)的特征是在老年人群中观察到的视觉障碍。一般描述了两种形式的疾病,萎缩(AMDa)和渗出形式(AMDe)。直到现在,这种疾病没有治愈性治疗方法。视网膜色素上皮(RPE)在年龄相关性黄斑变性的发病机理中起着重要作用。这里,通过比较来自健康个体或受AMDa或AMDe影响的个体的hiPSC-RPE的转录组概况,分析了RPE功能障碍在AMD发病和进展中的作用.该分析突出了三个比较组之间差异表达的近1000个基因。在这些基因中,已知33个基因与AMD发病机制有关。为了建立AMD遗传签名,我们关注与对照细胞相比在两个AMDa/e细胞系中差异表达的基因,并关注与脂质稳态相关的三个基因(ABCA1,RPN2,RB1CC1).这三个基因的水平表达差异不仅在对照和AMDa/e细胞系中发现,而且在AMDa和AMDe人群之间。
    Age-related macular degeneration (AMD) is characterized by visual impairment observed in elderly population. Two forms of the disease are generally described, the atrophic (AMDa) and exudative forms (AMDe). Up until now, no curative treatment is available for this disease. The retinal pigment epithelium (RPE) plays a central role in the pathogenesis of age-related macular degeneration. Here, involvement of RPE dysfunction in AMD onset and progression was analyzed by a comparison of transcriptome profiles of hiPSC-RPE derived from healthy individuals or individuals affected by AMDa or AMDe. The analysis highlighted almost 1000 genes differentially expressed between the three comparison groups. Among these genes, 33 genes were already known to be involved in AMD pathogenesis. To establish an AMD genetic signature, we focused on genes differentially expressed in both AMDa/e cell lines compared to control cells and focused on the three genes (ABCA1, RPN2, RB1CC1) that were related to lipidic homeostasis. Differences in level expression of these three genes are found not only in control and AMDa/e cell lines, but also between AMDa and AMDe populations.
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  • 文章类型: Journal Article
    考虑到总胆固醇(TC)和血管内皮素-1(ET-1)对儿童脓毒症结局的显著影响,本研究旨在探讨血浆胆固醇和血管内皮素-1水平与脓毒症严重程度之间的关系,并评估其临床意义。在这项研究中,我们检查了2019年2月至2021年4月间诊断为脓毒症的250例儿科患者,收集了他们血浆TC和ET-1水平的数据.根据观察到的结果,参与者分为2类:预后阳性的组(对照组,n=100)和预后阴性的组(n=50)。我们评估了血浆TC和ET-1水平在预测这些儿科患者预后中的意义。预后不良组患者的住院时间明显长于对照组,治疗费用明显高于对照组(P<0.05)。在入院的最初24小时内以及第3天和第7天,预后不良组的ET-1水平显着升高,而血浆TC水平明显低于对照组(P<0.05)。Spearman相关分析确定血浆TC和ET-1水平与儿童败血症严重程度之间存在显着相关性(P<0.05)。儿童败血症严重程度的诊断表现,通过曲线下面积(AUC)测量,血浆TC为0.805,ET-1水平为0.777,和0.938,当两者结合。这项研究强调了小儿脓毒症患者血浆TC和ET-1水平之间有意义的关系,表明这些生物标志物在预测患者预后方面非常有价值。这些患者中高水平的ET-1和低水平的TC表示严重的病情和不良的预后。
    Considering the significant impact of total cholesterol (TC) and vascular endothelin-1 (ET-1) on children sepsis outcomes, this research aimed to explore the association between the levels of plasma cholesterol and vascular endothelin-1 and the severity of sepsis and evaluated its clinical implications. In this study, we examined 250 pediatric patients diagnosed with sepsis between February 2019 and April 2021, collecting data on their plasma levels of TC and ET-1. Depending on the observed outcomes, the participants were divided into 2 categories: a group with a positive prognosis (control group, n = 100) and a group with a negative prognosis (n = 50). We assessed the significance of plasma TC and ET-1 levels in forecasting the outcomes for these pediatric patients. Patients in the group with a poor prognosis experienced notably longer hospital stays and higher treatment expenses than those in the control group (P < .05). Within the first 24 hours of admission and again on days 3 and 7, the levels of ET-1 were significantly higher in the poor prognosis group, whereas plasma TC levels were notably lower in comparison to the control group (P < .05). A Spearman correlation analysis identified a significant correlation between the levels of plasma TC and ET-1 and the severity of sepsis among the children (P < .05). The diagnostic performance for the severity of sepsis in children, as measured by the area under the curve (AUC), was 0.805 for plasma TC, 0.777 for ET-1 levels, and 0.938 when both were combined. This investigation underscores a meaningful relationship between the levels of plasma TC and ET-1 in pediatric sepsis patients, suggesting these biomarkers are highly valuable in predicting patient outcomes. High levels of ET-1 and low levels of TC in these patients signify a grave condition and a poor prognosis.
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  • 文章类型: Journal Article
    先前的流行病学研究表明,总胆固醇(TC)与胃癌(GC)之间存在潜在的负相关;然而,一些观察性研究显示结果相互矛盾,未能为TC和GC之间的因果关系提供明确的证据.因此,我们进行了2个样本的双向孟德尔随机化(MR)研究,以探讨这2个变量之间的遗传相关性和潜在的因果关系.我们利用大规模全基因组关联研究(GWAS)公共数据库筛选了与TC和GC相关的单核苷酸多态性(SNP)。使用5种MR分析方法分析因果关系:方差反加权(IVW),加权中位数,MR-Egger回归,加权模式,和简单的模式。此外,进行反向MR分析以评估反向因果关系的可能性.进行了敏感性分析,包括异质性测试,横向多重有效性测试,和遗漏一次测试。经过精心筛选,79个SNP被鉴定为工具变量(IVs)。IVW方法揭示了TC和GC之间的因果关系(OR=0.844;95%CI:0.741-0.961;P=0.01)。敏感性分析未检测到显着的水平多效性。尽管在正向MR分析中观察到异质性(IVW,Qp=0.0006),我们使用IVW随机效应模型作为主要分析方法,结果仍然可靠.此外,反向MR分析没有发现TC和GC之间存在反向因果关系的证据,有效排除GC对TC反向因果关系的影响。我们的MR研究提供了TC和GC之间因果关系的证据,这表明TC作为抗GC的保护因子,因为它与疾病负相关。
    Previous epidemiologic studies have suggested a potential negative correlation between total cholesterol (TC) and Gastric cancer (GC); however, several observational studies have shown conflicting results and have failed to provide definitive evidence for a causal relationship between TC and GC. Therefore, we conducted a 2-sample bidirectional Mendelian randomization (MR) study to explore the genetic correlation and potential causal relationship between the 2 variables. We screened for single nucleotide polymorphisms (SNPs) associated with TC and GC utilizing a large-scale genome-wide association study (GWAS) public database. The causal relationship was analyzed using 5 MR analysis methods: inverse variance weighting (IVW), weighted median, MR-Egger regression, weighted mode, and simple mode. Additionally, reverse MR analysis was performed to evaluate the possibility of reverse causality. Sensitivity analyses were conducted, including heterogeneity tests, horizontal multiple validity tests, and leave-one-out tests. After meticulous screening, 79 SNPs were identified as instrumental variables (IVs). The IVW method revealed a causal relationship between TC and GC (OR = 0.844; 95% CI: 0.741-0.961; P = .01). Sensitivity analyses did not detect significant horizontal pleiotropy. Though heterogeneity was observed in the forward MR analysis (IVW, Qp = 0.0006), the results remained reliable as we utilized the IVW random-effects model as the primary analytical method. Furthermore, inverse MR analysis found no evidence of reverse causality between TC and GC, effectively ruling out the influence of GC on the reverse causality of TC. Our MR study provided evidence of a causal association between TC and GC, suggesting that TC acts as a protective factor against GC due to its negative association with the disease.
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