apolipoprotein

载脂蛋白
  • 文章类型: Journal Article
    背景:糖尿病前期定义为正常葡萄糖代谢和糖尿病之间的高血糖状态。它也被认为是心血管疾病的诱发因素。载脂蛋白是脂蛋白的一个组成部分,其比值(ApoB/ApoA1比值)被认为是心血管疾病的独立危险因素。本研究旨在评估糖尿病前期患者载脂蛋白比率(ApoB/ApoA1比率)和脂蛋白比率(低密度脂蛋白胆固醇/高密度脂蛋白胆固醇(LDL-C/HDL-C)比率)与血糖水平的关系,并建立糖尿病前期患者载脂蛋白和脂蛋白比率与其血糖水平之间的关系。
    方法:对150名参与者进行了病例对照研究,75名糖尿病前期患者和75名明显健康的个体(没有糖尿病前期或糖尿病),从2023年1月1日至2023年12月30日。涉及的参数是空腹血清葡萄糖,胰岛素,血HbA1c%,HDL-C,LDL-C,载脂蛋白A,载脂蛋白B,和脂蛋白(a)(Lp(a)),用不同的原理测量。
    结果:糖尿病前期在男性中更为明显(58.7%),特别是40岁以上的人(74.7%)。平均Lp(a)(46.18±11.66mg/dl),LDL-C/HDL-C比值(1.74±0.96),在糖尿病前期个体中,ApoB/ApoA比值(1.10±0.62)明显较高。此外,在HbA1c水平(5.8-6.4%)和空腹血糖水平(100-125mg/dl)的糖尿病前期个体中,这些比率明显高于较低水平的个体.
    结论:糖尿病前期个体表现出显著升高的Lp(a)平均水平,以及与明显健康的个体相比,平均ApoB/ApoA1比值和平均LDL-C/HDL-C比值增加。
    BACKGROUND:  Prediabetes is defined as a hyperglycemic state between normal glucose metabolism and diabetes mellitus. It is also recognized as a predisposing factor for cardiovascular disease. Apolipoprotein is a constituent of lipoproteins, and its ratio levels (ApoB/ApoA1 ratio) are considered an independent risk factor for cardiovascular diseases. This study aimed to evaluate the apolipoprotein ratio (ApoB/ApoA1 ratio) and lipoprotein ratio (low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio) in prediabetes in relation to glycemic levels and establish the association between apolipoprotein and lipoprotein ratios in prediabetic individuals and their glycemic levels.
    METHODS:  A case-control study was conducted among 150 participants, 75 with prediabetes and 75 apparently healthy individuals (with no prediabetes or diabetes), from January 1, 2023 to December 30, 2023. The parameters involved are fasting serum glucose, insulin, blood HbA1c%, HDL-C, LDL-C, apolipoprotein A, apolipoprotein B, and lipoprotein(a) (Lp(a)), measured using different principles.
    RESULTS: Prediabetes was more predominant in males (58.7%), particularly those aged over 40 years (74.7%). The mean Lp(a) (46.18±11.66 mg/dl), LDL-C/HDL-C ratio (1.74±0.96), and ApoB/ApoA ratio (1.10±0.62) were significantly higher among prediabetic individuals. Moreover, these ratios were insignificantly higher in prediabetic individuals with HbA1c level (5.8-6.4%) and fasting glucose level (100-125 mg/dl) than those with lower levels.
    CONCLUSIONS: Prediabetic individuals exhibited a notably elevated average level of Lp(a), as well as increased mean ApoB/ApoA1 ratio and mean LDL-C/HDL-C ratio compared to individuals who were apparently healthy.
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  • 文章类型: Journal Article
    背景:酒精使用障碍(AUD)伴随炎症和认知功能下降的过程。载脂蛋白已成为与炎症过程和认知相关的新型靶化合物。
    方法:对禁欲至少一个月的禁欲AUD患者(n=33;72.7%男性)和健康对照(n=34;47.1%男性)进行了横断面研究。一系列血浆载脂蛋白(APOAI,APOAII,APOB,APOCII,APOE,APOJ和APOM),血浆炎症标志物(LPS,LBP),并调查了它们对认知和疾病存在的影响。
    结果:血浆APOAI水平较高,APOB,APOE和APOJ,以及促炎LPS,在AUD组中观察到,不论性别,而APOM水平低于对照组。分层逻辑回归分析,调整协变量(年龄,性别,education),APOM与AUD无认知障碍相关,并确定APOAI和APOM是该疾病存在或不存在的有力预测因子,分别。APOAI和APOM与酒精滥用变量或肝脏状态标志物无关,但它们与LPS(APOAI阳性;APOM阴性)和认知(APOAI阴性;APOM阳性)的相关性却相反。
    结论:与对照组相比,AUD受试者血浆中HDL成分APOAI和APOM的调节差异,在疾病识别以及与炎症和认知能力下降的关联中起着不同的作用。
    BACKGROUND: Alcohol use disorder (AUD) courses with inflammation and cognitive decline. Apolipoproteins have emerged as novel target compounds related to inflammatory processes and cognition.
    METHODS: A cross-sectional study was performed on abstinent AUD patients with at least 1 month of abstinence (n  = 33; 72.7% men) and healthy controls (n  = 34; 47.1% men). A battery of plasma apolipoproteins (APOAI, APOAII, APOB, APOCII, APOE, APOJ, and APOM), plasma inflammatory markers (LPS, LBP), and their influence on cognition and presence of the disorder were investigated.
    RESULTS: Higher levels of plasma APOAI, APOB, APOE, and APOJ, as well as the proinflammatory LPS, were observed in the AUD group, irrespective of sex, whereas APOM levels were lower vs controls. Hierarchical logistic regression analyses, adjusting for covariates (age, sex, education), associated APOM with the absence of cognitive impairment in AUD and identified APOAI and APOM as strong predictors of the presence or absence of the disorder, respectively. APOAI and APOM did not correlate with alcohol abuse variables or liver status markers, but they showed an opposite profile in their associations with LPS (positive for APOAI; negative for APOM) and cognition (negative for APOAI; positive for APOM) in the entire sample.
    CONCLUSIONS: The HDL constituents APOAI and APOM were differentially regulated in the plasma of AUD patients compared with controls, playing divergent roles in the disorder identification and associations with inflammation and cognitive decline.
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  • 文章类型: Journal Article
    关于载脂蛋白(Apos)与勃起功能障碍(ED)之间关联的现有研究主要依赖于观察性研究,并且在诊断ED时没有区分器质性和精神性原因。很难相信Apos在心理性ED中起作用。为了解决这些问题,我们的研究使用孟德尔随机化(MR)分析探讨了脂蛋白与ED之间的因果关系,并通过使用夜间阴茎肿胀和僵硬(NPTR)监测来区分器质性和心理性ED.多变量MR分析显示高密度脂蛋白(HDL),ApoA1和ApoB/A1伴ED(OR和95%CI为0.33(0.14-0.78),3.58(1.52-8.43),和0.30(0.13-0.66))。我们使用多变量分析和受试者工作特征(ROC)曲线对212例患者的数据进行了统计和分析.器质性ED患者的HDL水平明显降低,ApoA1和ApoA1/B,而器质性ED患者的ApoB和低密度脂蛋白(LDL)水平明显更高。采用ROC曲线评价Apos预测器质性ED风险的诊断价值。结果表明,ApoA1和ApoA1/B表现出良好的预测价值。HDL,在我们的研究中,ApoA1和ApoA1/B已被确定为ED的危险因素。此外,我们的研究强调了ApoA1和ApoA1/ApoB在有机ED开发中的重要性,并建议将其用作评估与有机ED相关风险的指标.
    The existing research on the association between apolipoproteins (Apos) and erectile dysfunction (ED) primarily relies on observational studies and does not distinguish between organic and psychogenic causes when diagnosing ED. It is difficult to believe that Apos play a role in psychogenic ED. To address these issues, our study explored the causal relationship between lipoproteins and ED using Mendelian randomization (MR) analysis and differentiate between organic and psychogenic ED through the use of nocturnal penile tumescence and rigidity (NPTR) monitoring. Multivariate MR analysis revealed significant causal associations between high-density lipoprotein (HDL), Apo A1, and Apo B/A1 with ED (OR and 95% CI were 0.33 (0.14-0.78), 3.58 (1.52-8.43), and 0.30 (0.13-0.66)). we conducted statistical and analytical analyses on the data of 212 patients using multivariate analyses and receiver operating characteristic (ROC) curves. Patients with organic ED had significantly lower levels of HDL, Apo A1 and Apo A1/B, whereas patients with organic ED had considerably higher levels of Apo B and low-density lipoprotein (LDL). The diagnostic value of Apos in predicting the risk of organic ED was evaluated using ROC curves. The results indicated that Apo A1 and Apo A1/B demonstrated good predictive value. HDL, Apo A1, and Apo A1/B have been identified as risk factors for ED in our study. Furthermore, our research highlights the significance of Apo A1 and Apo A1/Apo B in the development of organic ED and suggests their potential use as indicators to assess the risks associated with organic ED.
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  • 文章类型: Journal Article
    目标:在单胎孕妇中,已证实母体载脂蛋白水平异常是早产的危险因素。然而,目前尚无双胎孕妇的相关研究。
    方法:这项单中心回顾性研究包括2019年1月至2020年12月间分娩的743名二胎双胎孕妇。妊娠37周前分娩的双胞胎被归类为早产组,而在妊娠37周时或之后分娩的患者被归类为足月组。孕妇血清载脂蛋白A1(ApoA1)水平,载脂蛋白B(ApoB)水平,在孕早期(6-14周)测量ApoB/ApoA1比值,妊娠中期(18-28周)和妊娠中期(28周后)。我们进行了SPSS分析来评估ApoA1水平之间的相关性,ApoB水平,ApoB/ApoA1比值与早产。
    结果:在743名包括双胎双胎孕妇中,53.57%(398/743)早产。与术语组相比,妊娠晚期ApoA1水平较低(p<0.001),而ApoB/ApoA1比值在早产组的第2个月(p=0.01)和第3个月(p=0.001)较高。当早产被归类为医源性早产和自发性早产时,结果相似。在按孕前BMI分层的分析中,仅在超重/肥胖双胎孕妇亚组中,早产风险较高与妊娠中期和中期ApoA1水平低和ApoB/ApoA1比值高相关.
    结论:在第二和第三孕期,低ApoA1水平和高ApoB/ApoA1比率与超重/肥胖双胎孕妇早产发生率高相关。
    OBJECTIVE: In singleton-pregnant women, abnormal maternal apolipoprotein levels have been confirmed as a risk factor for preterm birth. However, there are currently no studies on the relationship of the related research in twin-pregnant women.
    METHODS: This single-center retrospective study included 743 dichorionic twin-pregnant women who delivered between January 2019 and December 2020. Twins delivered before 37 weeks gestation were categorized as the preterm group, while those delivered at or after 37 weeks gestation were classified as the term group. Maternal serum apolipoprotein A1 (ApoA1) levels, apolipoprotein B (ApoB) levels, and the ApoB/ApoA1 ratio were measured in the first trimester(6-14 weeks), the second trimester(18-28 weeks) and the third trimester(after 28 weeks). We conducted SPSS analysis to evaluate the correlation between ApoA1 levels, ApoB levels, the ApoB/ApoA1 ratio and preterm birth.
    RESULTS: Among the 743 included dichorionic twin-pregnant women, 53.57 % (398/743) delivered preterm. Compared with the term group, the ApoA1 levels in the third trimester were lower (p < 0.001), while the Apo B/ApoA1 ratio was higher in the second (p = 0.01) and third trimesters in the preterm group (p = 0.001). When preterm birth was categorized as iatrogenic and spontaneous preterm birth, the results were similar. In the analysis stratified by prepregnancy BMI, a higher risk of preterm birth was associated with low ApoA1 levels and a high Apo B/ApoA1 ratio in the second and third trimesters only among the subgroup of overweight/obese dichorionic twin-pregnant women.
    CONCLUSIONS: Low ApoA1 levels and a high Apo B/ApoA1 ratio during the second and third trimesters were associated with a high incidence of preterm birth for overweight/obese dichorionic twin-pregnant women.
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  • 文章类型: Journal Article
    背景:在种族和地理上不同的人群中,全面的血液脂蛋白谱及其与冠心病(CHD)的关系仍未得到充分研究。
    结果:我们在3438名个体(1719对)中进行了冠心病的巢式病例对照研究,包括1084名美国白人(542对),1244美国黑人(622对),和1110名中国成年人(555对)。我们检查了36种血浆脂质,脂蛋白,和载脂蛋白,核磁共振波谱测量,根据人口统计学,所有参与者和亚组中的冠心病事件,生活方式,和代谢健康状况,使用条件或无条件逻辑回归校正潜在的混杂因素。常规测量血脂,也就是说,总胆固醇,甘油三酯,低密度脂蛋白胆固醇,高密度脂蛋白胆固醇,每个都与冠心病相关,所有参与者的比值比(ORs)分别为1.33、1.32、1.24和0.79/1-SD.17种脂蛋白生物标志物显示出数字上比常规脂质更强的关联,所有参与者中每1-SD的ORs范围为1.35至1.57,OR为阴性0.78(所有错误发现率<0.05),包括载脂蛋白B100与载脂蛋白A1的比率(OR,1.57[95%CI,1.45-1.7]),低密度脂蛋白甘油三酯(OR,1.55[95%CI,1.43-1.69]),和载脂蛋白B(OR,1.49[95%CI,1.37-1.62])。所有这些关联在种族群体和其他按年龄定义的亚组之间是显著和一致的,性别,吸烟,肥胖,和代谢健康状况,包括常规测量的脂质水平正常的个体。
    结论:我们的研究强调了几种脂蛋白生物标志物,包括载脂蛋白B/载脂蛋白A1比率,载脂蛋白B,和低密度脂蛋白甘油三酯,与冠心病事件密切相关。我们的结果表明,全面的脂蛋白测量可以补充标准脂质面板,以告知不同人群的CHD风险。
    BACKGROUND: Comprehensive blood lipoprotein profiles and their association with incident coronary heart disease (CHD) among racially and geographically diverse populations remain understudied.
    RESULTS: We conducted nested case-control studies of CHD among 3438 individuals (1719 pairs), including 1084 White Americans (542 pairs), 1244 Black Americans (622 pairs), and 1110 Chinese adults (555 pairs). We examined 36 plasma lipids, lipoproteins, and apolipoproteins, measured by nuclear magnetic resonance spectroscopy, with incident CHD among all participants and subgroups by demographics, lifestyle, and metabolic health status using conditional or unconditional logistic regression adjusted for potential confounders. Conventionally measured blood lipids, that is, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol, were each associated with incident CHD, with odds ratios (ORs) being 1.33, 1.32, 1.24, and 0.79 per 1-SD increase among all participants. Seventeen lipoprotein biomarkers showed numerically stronger associations than conventional lipids, with ORs per 1-SD among all participants ranging from 1.35 to 1.57 and a negative OR of 0.78 (all false discovery rate <0.05), including apolipoprotein B100 to apolipoprotein A1 ratio (OR, 1.57 [95% CI, 1.45-1.7]), low-density lipoprotein-triglycerides (OR, 1.55 [95% CI, 1.43-1.69]), and apolipoprotein B (OR, 1.49 [95% CI, 1.37-1.62]). All these associations were significant and consistent across racial groups and other subgroups defined by age, sex, smoking, obesity, and metabolic health status, including individuals with normal levels of conventionally measured lipids.
    CONCLUSIONS: Our study highlighted several lipoprotein biomarkers, including apolipoprotein B/ apolipoprotein A1 ratio, apolipoprotein B, and low-density lipoprotein-triglycerides, strongly and consistently associated with incident CHD. Our results suggest that comprehensive lipoprotein measures may complement the standard lipid panel to inform CHD risk among diverse populations.
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  • 文章类型: Journal Article
    补体部分5a(C5a)的作用,白介素(IL)-9和载脂蛋白(apo)A-IV作为慢性自发性荨麻疹(CSU)疾病严重程度和抗组胺反应的生物标志物仍然难以捉摸。
    为了确定C5a的作用,IL-9和apoA-IV作为预测CSU患者疾病严重程度和抗组胺反应的潜在生物标志物。
    这是一项对95名患者和42名对照的前瞻性观察性研究。血清C5a分析,使用酶联免疫吸附测定试剂盒完成IL-9和载脂蛋白A-IV。此外,评估所有患者的血清IgE和抗甲状腺过氧化物酶(TPO)水平。所有患者在基线开始口服左西替利嗪5mg,并根据反应将剂量向上滴定至最大20mg。根据疾病反应,将患者分为抗组胺反应者或非反应者。血清学标记,血清IgE,抗TPO与基线疾病严重程度和抗组胺反应相关。
    C5a水平在病例中显著高于对照组(P=0.004)。抗组胺反应者的IL-9水平明显高于非反应者(P=0.008)。基线荨麻疹严重程度与IL-9(ρ=0.277,P=0.007)和apoA-IV(ρ=-0.271,P=0.008)水平呈显著正相关和负相关,分别。血清IgE(P=0.031)和抗TPO(P=0.039)的水平明显高于抗组胺无反应者。
    IL-9和载脂蛋白A-IV可能是预测荨麻疹严重程度的潜在新型生物标志物。较高的IL-9可能是抗组胺反应的预测因子。抗TPO和血清IgE升高可能预示抗组胺反应不良。
    UNASSIGNED: Role of complement fraction 5a (C5a), interleukin (IL)-9, and apolipoprotein (apo) A-IV as biomarkers of disease severity and antihistamine response in chronic spontaneous urticaria (CSU) remains elusive.
    UNASSIGNED: To identify the role of C5a, IL-9, and apo A-IV as potential biomarkers in predicting disease severity and antihistamine response in CSU patients.
    UNASSIGNED: This was a prospective observational study of 95 patients and 42 controls. Serum analysis of C5a, IL-9, and apo A-IV was done using enyzme linked immunosorbent assay kits. Also, serum IgE and anti-thyroid peroxidase (TPO) levels were assessed in all patients. All patients were started on oral levocetirizine 5 mg at baseline and dose was titrated upwards to maximum of 20 mg based on response. Patients were categorized into antihistamine responders or nonresponders as per their disease response. Serological markers, serum IgE, and anti-TPO were correlated with baseline disease severity and antihistamine response.
    UNASSIGNED: C5a levels were significantly higher in cases as compared to controls (P = 0.004). Significantly higher IL-9 levels were observed in antihistamine responders than nonresponders (P = 0.008). Baseline urticaria severity demonstrated a statistically significant positive and negative correlations with IL-9 (ρ = 0.277, P = 0.007) and apo A-IV (ρ = -0.271, P = 0.008) levels, respectively. Levels of serum IgE (P = 0.031) and anti-TPO (P = 0.039) were significantly higher in antihistamine nonresponders compared to responders.
    UNASSIGNED: IL-9 and apo A-IV might be potential novel biomarkers to predict urticaria severity. Higher IL-9 might be a predictor of antihistamine response. Elevated anti-TPO and serum IgE might predict poor antihistamine response.
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  • 文章类型: Journal Article
    背景:合并症降低了痴呆症患者和护理人员的生活质量。一些合并症与痴呆症具有遗传基础。
    目的:本研究的目的是评估不同亚型痴呆患者的合并症,以便更好地了解痴呆的发病机制。
    方法:共纳入298例痴呆患者。我们收集了一些常见的合并症。我们根据临床诊断分析痴呆患者合并症的差异,使用单变量和多变量方法的发病年龄(早发病:<65岁和晚发病:≥65岁)和载脂蛋白(APOE)基因型。
    结果:在298名参与者中,有183个阿尔茨海默病(AD),40血管性痴呆(VaD),37额颞叶痴呆(FTLD),20路易体痴呆(LBD),和18种其他类型的痴呆症。根据发病年龄,早发性痴呆156例,晚发性痴呆142例。在所有痴呆患者中观察到的最常见的合并症是高脂血症(68.1%),高血压(39.9%),失眠(21.1%),糖尿病(19.5%),和听力障碍(18.1%)。与AD患者(分别为p=0.002,p<0.001)和FTLD患者(分别为p=0.028,p=0.004)相比,VaD患者的高血压和脑血管病患病率更高。此外,与早发性痴呆患者相比,晚发性痴呆患者的合并症负担较高.据观察,APOE4携带者患失眠的可能性较小(p=0.031)。
    结论:痴呆患者普遍存在合并症,高脂血症,高血压,失眠,糖尿病,听力障碍是最常见的。不同痴呆亚型之间存在合并症差异。
    BACKGROUND: Comorbidities reduce quality of life for people with dementia and caregivers. Some comorbidities share a genetic basis with dementia.
    OBJECTIVE: The objective of this study is to assess comorbidity in patients with different dementia subtypes in order to better understand the pathogenesis of dementias.
    METHODS: A total of 298 patients with dementia were included. We collected some common comorbidities. We analyzed the differences in comorbidities among patients with dementia according to clinical diagnosis, age of onset (early-onset: < 65 and late-onset: ≥65 years old) and apolipoprotein (APOE) genotypes by using the univariate and multivariate approaches.
    RESULTS: Among 298 participants, there were 183 Alzheimer\'s disease (AD), 40 vascular dementia (VaD), 37 frontotemporal dementia (FTLD), 20 Lewy body dementia (LBD), and 18 other types of dementia. Based on age of onset, 156 cases had early-onset dementia and 142 cases had late-onset dementia. The most common comorbidities observed in all dementia patients were hyperlipidemia (68.1%), hypertension (39.9%), insomnia (21.1%), diabetes mellitus (19.5%), and hearing impairment (18.1%). The prevalence of hypertension and cerebrovascular disease was found to be higher in patients with VaD compared to those with AD (p = 0.002, p < 0.001, respectively) and FTLD (p = 0.028, p = 0.004, respectively). Additionally, patients with late-onset dementia had a higher burden of comorbidities compared to those with early-onset dementia. It was observed that APOE ɛ4/ɛ4 carriers were less likely to have insomnia (p = 0.031).
    CONCLUSIONS: Comorbidities are prevalent in patients with dementia, with hyperlipidemia, hypertension, insomnia, diabetes, and hearing impairment being the most commonly observed. Comorbidity differences existed among different dementia subtypes.
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  • 文章类型: Journal Article
    由于网络神经科学可以在神经成像水平上捕获APOE变异性的系统性影响,这项研究调查了ε4携带者和非携带者在正常衰老和阿尔茨海默氏痴呆(AD)之间的连续体中的基于网络的认知内表型。我们假设APOE-ε4对认知功能的影响可以通过测量图论中心性来可靠地捕获。在8118个对照中计算了认知网络,3482名MCI患者和4573名AD患者,在国家阿尔茨海默氏症协调中心(NACC)数据库中招募。选择节点中心性作为感兴趣的神经功能读出。ε4-载波-vs.在使用统一数据集的版本1或版本2评估的两个独立的NACC子队列中测试非携带者差异。通过对两个子队列中MCI患者的逻辑记忆节点的分析,发现了显着的APOE依赖性效应。虽然非承运人在立即召回和延迟召回中表现出同等的中心地位,后者在携带者中的重要性明显较低(v1:自举置信区间0.107-0.667,p<0.001;v2:自举置信区间0.018-0.432,p<0.001).这表明,在承运人中,延迟召回是,总的来说,与其他认知得分的相关性明显较弱。这些发现在唯一的遗忘型MCI患者的亚组中重复(n=2971),独立于网络社区的差异,临床严重程度或其他人口统计学因素。在其他两个诊断组中没有发现效果。当患者被临床分类为MCI时,APOE-ε4会影响认知网络的节点特性。这凸显了通过网络神经科学方法表征风险因素对更广泛的认知网络的影响的重要性。
    As network neuroscience can capture the systemic impact of APOE variability at a neuroimaging level, this study investigated the network-based cognitive endophenotypes of ε4-carriers and non-carriers across the continuum between normal ageing and Alzheimer\'s dementia (AD). We hypothesised that the impact of APOE-ε4 on cognitive functioning can be reliably captured by the measurement of graph-theory centrality. Cognitive networks were calculated in 8118 controls, 3482 MCI patients and 4573 AD patients, recruited in the National Alzheimer\'s Coordinating Center (NACC) database. Nodal centrality was selected as the neurofunctional readout of interest. ε4-carrier-vs.-non-carrier differences were tested in two independent NACC sub-cohorts assessed with either Version 1 or Version 2 of the Uniform Data Set neuropsychological battery. A significant APOE-dependent effect emerged from the analysis of the Logical-Memory nodes in MCI patients in both sub-cohorts. While non-carriers showed equal centrality in immediate and delayed recall, the latter was significantly less central among carriers (v1: bootstrapped confidence interval 0.107-0.667, p < 0.001; v2: bootstrapped confidence interval 0.018-0.432, p < 0.001). This indicates that, in carriers, delayed recall was, overall, significantly more weakly correlated with the other cognitive scores. These findings were replicated in the sub-groups of sole amnestic-MCI patients (n = 2971), were independent of differences in network communities, clinical severity or other demographic factors. No effects were found in the other two diagnostic groups. APOE-ε4 influences nodal properties of cognitive networks when patients are clinically classified as MCI. This highlights the importance of characterising the impact of risk factors on the wider cognitive network via network-neuroscience methodologies.
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  • 文章类型: Journal Article
    高密度脂蛋白(HDLs)是预测和治疗动脉粥样硬化性心血管疾病(ASCVD)的有希望的目标,因为它们介导从积聚在脉管系统中的富含脂质的巨噬细胞中去除多余的胆固醇。HDLs的这种功能特性,称为胆固醇流出能力(CEC),与ASCVD成反比。HDLs在组成上是不同的,与>250种不同的蛋白质相关联,但他们对CEC的相对贡献仍然知之甚少。我们的目标是鉴定和定义调节人类CEC的关键HDL相关蛋白。在基于多种族人群的达拉斯心脏研究(DHS)队列中,血浆HDL的蛋白质组学特征在15年内表现出持续的极高(>=90%)或极低的CEC(<=10%)。载脂蛋白(Apo)A-I相关ApoC-II的水平,ApoC-III,ApoA-IV与CEC在高(分别为r=0.49、0.41和-0.21)和低(分别为r=-0.46、-0.41和0.66)CEC组中存在差异相关(p表示异质性(pHet)分别为0.03、0.04和0.003)。Further,我们观察到ApoA-I和ApoC-III的水平,补体C3(CO3),ApoE,在低CEC组中的个体中,纤溶酶原(PLMG)与CEC呈负相关(对于具有这些蛋白质的亚种,r=-0.11至-0.25与对于缺乏这些蛋白质的亚种,r=0.58至0.65;对于异质性,p<0.05)。这些发现表明,HDLs上特定蛋白质的富集,因此,HDLs的不同亚种,差异调节从脉管系统中去除胆固醇。
    High-density lipoproteins (HDLs) are promising targets for predicting and treating atherosclerotic cardiovascular disease (ASCVD), as they mediate removal of excess cholesterol from lipid-laden macrophages that accumulate in the vasculature. This functional property of HDLs, termed cholesterol efflux capacity (CEC), is inversely associated with ASCVD. HDLs are compositionally diverse, associating with >250 different proteins, but their relative contribution to CEC remains poorly understood. Our goal was to identify and define key HDL-associated proteins that modulate CEC in humans. The proteomic signature of plasma HDL was quantified in 36 individuals in the multi-ethnic population-based Dallas Heart Study (DHS) cohort that exhibited persistent extremely high (>=90th%) or extremely low CEC (<=10th%) over 15 years. Levels of apolipoprotein (Apo)A-I associated ApoC-II, ApoC-III, and ApoA-IV were differentially correlated with CEC in high (r = 0.49, 0.41, and -0.21 respectively) and low (r = -0.46, -0.41, and 0.66 respectively) CEC groups (p for heterogeneity (pHet) = 0.03, 0.04, and 0.003 respectively). Further, we observed that levels of ApoA-I with ApoC-III, complement C3 (CO3), ApoE, and plasminogen (PLMG) were inversely associated with CEC in individuals within the low CEC group (r = -0.11 to -0.25 for subspecies with these proteins vs. r = 0.58 to 0.65 for subspecies lacking these proteins; p < 0.05 for heterogeneity). These findings suggest that enrichment of specific proteins on HDLs and, thus, different subspecies of HDLs, differentially modulate the removal of cholesterol from the vasculature.
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  • 文章类型: Journal Article
    背景:浆细胞肿瘤是一组血液肿瘤,通常在老年人群中发展。在人群研究中已经确定了胆固醇水平与血液系统恶性肿瘤之间的关系。然而,目前尚不清楚欧洲血统中胆固醇水平与浆细胞肿瘤之间是否存在关系。
    方法:前瞻性队列包括来自英国生物银行的502,507名个体,他们在2019年之前进行了随访,并评估了总胆固醇(TC)水平。低密度脂蛋白(LDL)水平,高密度脂蛋白(HDL)水平,载脂蛋白A(ApoA)和载脂蛋白B(ApoB)作为浆细胞肿瘤的危险因素,采用Cox比例风险回归和限制性三次样条模型。我们还使用了两个孟德尔随机样本来确定胆固醇水平是否对发展中的浆细胞肿瘤有因果关系。
    结果:我们在英国生物库14.2年的随访中观察到1819例浆细胞肿瘤病例。在我们的研究中,我们发现基线时较高的血清胆固醇水平与较低的浆细胞肿瘤风险相关。我们在这项研究中分析的所有血脂谱与浆细胞肿瘤风险呈负相关(所有ptrend<0.005),但甘油三酯没有这种关联。然而,基因预测的血清LDL没有暗示性关联,HDL,和多发性骨髓瘤的总胆固醇水平。
    结论:低血清总胆固醇,LDL,HDL,ApoA,和ApoB水平都与浆细胞肿瘤的风险增加有关。
    Plasma cell neoplasms are a group of hematologic neoplasms that often develop in the elderly population. The relationship between cholesterol levels and hematologic malignancy has been identified in population studies. However, it is still unclear if there is a relationship between cholesterol levels and plasma cell neoplasm in European ancestry.
    Prospective cohorts included 502,507 individuals from the UK Biobank who were followed up to 2019 and assessed total cholesterol(TC) levels, low-density lipoprotein (LDL) levels, high-density lipoprotein (HDL) levels, apolipoprotein A (ApoA) and apolipoprotein B (ApoB) as risk factors for plasma cell neoplasms with Cox proportional hazard regression and restricted cubic spline model. We also used two-sample Mendelian randomization to determine if the cholesterol level has a causal effect on developing plasma cell neoplasms.
    We observed 1819 plasma cell neoplasm cases during 14.2 years of follow-up in the UK Biobank. We found higher blood serum cholesterol levels at baseline were associated with a lower risk of plasma cell neoplasm in our study. All lipid profiles we analyzed in this study were inversely associated with plasma cell neoplasm risk (all ptrend  <0.005) but triglycerides did not have such association. However, there was no suggestive association of genetically predicted serum LDL, HDL, and total cholesterol levels with multiple myeloma.
    Low serum total cholesterol, LDL, HDL, ApoA, and ApoB levels were all associated with increasing the risk of plasma cell neoplasm.
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