Low-density lipoprotein receptor-related protein 2(LRP2)is required for lipid export in the midgut of the migratory locust,Locusta migratoria

Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis.However,little is known about the role of LRP2 in lipid homeostasis in insects.In the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage.Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut.Using RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated nymphs.The results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and hemolymph.Furthermore,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs.Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts.

Synthetic high-density lipoprotein(sHDL):a bioinspired nanotherapeutics for managing periapical bone inflammation

Apical periodontitis(AP)is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth(i.e.,dental pulp tissue),resulting in inflammation and apical bone resorption affecting 50%of the worldwide population,with more than 15 million root canals performed annually in the United States.Current treatment involves cleaning and decontaminating the infected tissue with chemo-mechanical approaches and materials introduced years ago,such as calcium hydroxide,zinc oxide–eugenol,or even formalin products.Here,we present,for the first time,a nanotherapeutics based on using synthetic highdensity lipoprotein(sHDL)as an innovative and safe strategy to manage dental bone inflammation.sHDL application in concentrations ranging from 25μg to 100μg/mL decreases nuclear factor Kappa B(NF-κB)activation promoted by an inflammatory stimulus(lipopolysaccharide,LPS).Moreover,sHDL at 500μg/mL concentration markedly decreases in vitro osteoclastogenesis(P<0.001),and inhibits IL-1α(P=0.027),TNF-α(P=0.004),and IL-6(P<0.001)production in an inflammatory state.Notably,sHDL strongly dampens the Toll-Like Receptor signaling pathway facing LPS stimulation,mainly by downregulating at least 3-fold the pro-inflammatory genes,such as Il1b,Il1a,Il6,Ptgs2,and Tnf.In vivo,the lipoprotein nanoparticle applied after NaOCl reduced bone resorption volume to(1.3±0.05)mm^(3) and attenuated the inflammatory reaction after treatment to(1090±184)cells compared to non-treated animals that had(2.9±0.6)mm^(3)(P=0.0123)and(2443±931)cells(P=0.004),thus highlighting its promising clinical potential as an alternative therapeutic for managing dental bone inflammation.

Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke

Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s disease.However,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke.To address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models.First,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis.We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation.Second,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus.Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype.Finally,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte phenotype.These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.

Monocyte to High-density Lipoprotein Cholesterol Ratio as a Predictor of Nonalcoholic Fatty Liver Disease in Childhood Obesity

Objective Inflammation is involved in the development and progression of nonalcoholic fatty liver disease(NAFLD).The monocyte to high-density lipoprotein cholesterol ratio(MHR)has emerged as a marker for various inflammation-related diseases.The aim of the present study was to investigate the association between the MHR and NAFLD in a population with childhood obesity.Methods Based on hepatic ultrasound,a total of 504 children with obesity(357 with NAFLD and 147 without NAFLD)were included in the study.The correlation between the MHR and NAFLD risk factors was assessed by Pearson’s and Spearman’s analyses.Multivariate stepwise logistic regression analyses were conducted to explore the association between the MHR and the risk of NAFLD.Results The MHR in patients with NAFLD was significantly greater than that in patients without NAFLD[0.52(0.44-0.67)versus 0.44(0.34-0.57),P<0.001].Multivariate stepwise logistic regression analysis demonstrated that the MHR[odds ratio(OR):1.033,95%confidence interval(CI):1.015-1.051;P<0.001]was an independent predictor of NAFLD in childhood obesity patients,as were age(OR:1.205,95%CI:1.059-1.371;P=0.005],waist circumference[OR:1.037,95%CI:1.008-1.067;P=0.012],and alanine transaminase[OR:1.067,95%CI:1.045-1.089;P<0.001].Additionally,MHR quartiles showed a significant positive association with the incidence of NAFLD after adjusting for potential confounding factors.Conclusion The present study showed that the MHR may serve as an available and useful indicator of NAFLD in individuals with childhood obesity.

Initial decrease in the lipoprotein(a)level is a novel prognostic biomarker in patients with acute coronary syndrome

BACKGROUND Lipoprotein(a)[Lp(a)]is a causal risk factor for atherosclerotic cardiovascular diseases;however,its role in acute coronary syndrome(ACS)remains unclear.AIM To investigate the hypothesis that the Lp(a)levels are altered by various conditions during the acute phase of ACS,resulting in subsequent cardiovascular events.METHODS From September 2009 to May 2016,377 patients with ACS who underwent emergent coronary angiography,and 249 who completed≥1000 d of follow-up were enrolled.Lp(a)levels were measured using an isoform-independent assay at each time point from before percutaneous coronary intervention(PCI)to 48 h after PCI.The primary endpoint was the occurrence of major adverse cardiac events(MACE;cardiac death,other vascular death,ACS,and non-cardiac vascular events).RESULTS The mean circulating Lp(a)level decreased significantly from pre-PCI(0 h)to 12 h after(19.0 mg/dL to 17.8 mg/dL,P<0.001),and then increased significantly up to 48 h after(19.3 mg/dL,P<0.001).The changes from 0 to 12 h[Lp(a)Δ0-12]significantly correlated with the basal levels of creatinine[Spearman’s rank correlation coefficient(SRCC):-0.181,P<0.01]and Lp(a)(SRCC:-0.306,P<0.05).Among the tertiles classified according to Lp(a)Δ0-12,MACE was significantly more frequent in the lowest Lp(a)Δ0-12 group than in the remaining two tertile groups(66.2%vs 53.6%,P=0.034).A multivariate analysis revealed that Lp(a)Δ0-12[hazard ratio(HR):0.96,95%confidence interval(95%CI):0.92-0.99]and basal creatinine(HR:1.13,95%CI:1.05-1.22)were independent determinants of subsequent MACE.CONCLUSION Circulating Lp(a)levels in patients with ACS decreased significantly after emergent PCI,and a greater decrease was independently associated with a worse prognosis.

Monocyte to high-density lipoprotein cholesterol ratio as a predictor of the activity of thyroid-associated ophthalmopathy

AIM:To evaluate the relationship between monocyte to high-density lipoprotein cholesterol ratio(MHR)and the disease activity of thyroid-associated ophthalmopathy(TAO).METHODS:A total of 87 patients were classified into two groups based on clinical activity score(CAS)scoring criteria:high CAS group(n=62,the CAS score was≥3);low CAS group(n=25,the CAS score was<3).In addition,a group of healthy people(n=114)were included to compared the MHR.Proptosis,MHR,average signal intensity ratio(SIR),average lacrimal gland(LG)-SIR,average extraocular muscles(EOM)area from 87 patients with TAO were calculated in magnetic resonance imaging(MRI),and compared between these two groups.Correlation testing was utilized to evaluate the association of parameters among the clinical variables.RESULTS:Patients in high CAS group had a higher proptosis(P=0.041)and MHR(P=0.048).Compared to the healthy group,the MHR in the TAO group was higher(P=0.001).Correlation testing declared that CAS score was strongly associated with proptosis and average SIR,and MHR was positively associated with CAS score,average SIR,and average LG-SIR.The area under the receiver operating characteristic curve(AUC)of MHR was 0.6755.CONCLUSION:MHR,a novel inflammatory biomarker,has a significant association with CAS score and MRI imaging(average SIR and LG-SIR)and it can be a new promising predictor during the active phase of TAO.

Association between sensitivity to thyroid hormones and non-highdensity lipoprotein cholesterol levels in patients with type 2 diabetes mellitus

BACKGROUND Dyslipidemia and type 2 diabetes mellitus(T2DM)are chronic conditions with substantial public health implications.Effective management of lipid metabolism in patients with T2DM is critical.However,there has been insufficient attention given to the relationship between thyroid hormone sensitivity and dyslipidemia in the T2DM population,particularly concerning non-high-density lipoprotein cholesterol(non-HDL-C).AIM To clarify the association between thyroid hormone sensitivity and dyslipidemia in patients with T2DM.METHODS In this cross-sectional study,thyroid hormone sensitivity indices,the thyroid feedback quantile-based index(TFQI),the thyroid-stimulating hormone index(TSHI),the thyrotrophic T4 resistance index(TT4RI),and the free triiodothyronine(FT3)/free thyroxine(FT4)ratio were calculated.Logistic regression analysis was performed to determine the associations between those composite indices and non-HDL-C levels.Random forest variable importance and Shapley Additive Explanations(SHAP)summary plots were used to identify the strength and direction of the association between hyper-non-HDL-C and its major predictor.RESULTS Among the 994 participants,389(39.13%)had high non-HDL-C levels.Logistic regression analysis revealed that the risk of hyper-non-HDL-C was positively correlated with the TFQI(OR:1.584;95%CI:1.088-2.304;P=0.016),TSHI(OR:1.238;95%CI:1.034-1.482;P=0.02),and TT4RI(OR:1.075;95%CI:1.006-1.149;P=0.032)but was not significantly correlated with the FT3/FT4 ratio.The relationships between composite indices of the thyroid system and non-HDL-C levels differed according to sex.An increased risk of hyper-non-HDL-C was associated with elevated TSHI levels in men(OR:1.331;95%CI:1.003-1.766;P=0.048)but elevated TFQI levels in women(OR:2.337;95%CI:1.4-3.901;P=0.001).Among the analyzed variables,the average SHAP values were highest for TSHI,followed by TT4RI.CONCLUSION Impaired sensitivity to thyroid hormones was associated with high non-HDL-C levels in patients with T2DM.

Correlation of Helicobacter pylori infection with high-density lipoprotein cholesterol levels and pulse wave conduction velocity

Background:Helicobacter pylori(HP)is associated with several gastrointestinal diseases,including peptic ulcer diseases and gastric cancer,and non-gastrointestinal diseases such as hypertension and Alzheimer's disease.However,the relationship between HP and lipid metabolism and atherosclerosis remains unclear.This study aims to investigate the association between H.pylori infection and high-density lipoprotein cholesterol levels and pulse wave conduction velocity.Methods:This is a report of a cross-sectional study that collected data from 2,827 participants.The data collected included results of life questionnaires,laboratory tests,13C-urea breath test(13C-UBT),and pulse wave conduction velocity test.Based on the results of the 13C-UBT test,the subjects were divided into two groups:the HP-uninfected group(HP−)and the HP-infected group(HP+).The study compared the differences in HDL-C levels and brachial-ankle pulse wave velocity(baPWV)between the two groups.One-way regression analysis was used to identify potential factors affecting HDL-C levels in the study population.Multiple regression equations were presented to analyze whether HP infection was an independent risk factor for abnormal HDL-C metabolism in the population.Results:Univariate analysis demonstrated that high-density lipoprotein cholesterol(HDL-C)levels were significantly lower in the HP+group compared to the HP−group,with a mean difference ofβ=−18.1 mg/dl(95%CI:−19.3 to−17.0,P<0.001).After adjusting for all variables,the HDL-C levels remained lower in the HP+group compared to the HP-group,with a mean difference ofβ=−17.4 mg/dl(95%CI:−18.2 to−16.7,P<0.001).These findings suggest that H.pylori infection is independently associated with abnormal HDL-C metabolism.Additionally,brachial-ankle pulse wave velocity(baPWV)was higher in the HP+group than in the HP−group on both sides.On the right side,the baPWV was 1,713.4±231.4 cm/s in the HP+group compared to 1,542.8±237.5 cm/s in the HP−group(t=−18.30,P<0.001).On the left side,the baPWV was 1,743.7±238.8 cm/s in the HP+group compared to 1,562.8±256.3 cm/s in the HP−group(t=−18.23,P<0.001).These results indicate a significant association between H.pylori infection and increased arterial stiffness,as measured by baPWV.Conclusion:Helicobacter pylori infection is associated with a decrease in high-density lipoprotein cholesterol levels and an increase in pulse wave conduction velocity.

Lp-PLA2、hs-CRP和FIB联合检测在急性脑梗死诊断中的应用

目的探讨血浆脂蛋白相关磷脂酶A2(Lp-PLA2)、超敏C反应蛋白(hs-CRP)和纤维蛋白原(FIB)联合检测在急性脑梗死诊断中的临床价值。方法收集我院240例急性脑梗死的住院患者作为研究对象(脑梗组),以100例门诊体检健康人员为对照组,比较两组人群的一般临床数据及检验结果,记录患者入院时的NIHSS评分。分析急性脑梗死患者血浆Lp-PLA2、hs-CRP和FIB水平与其神经功能缺损程度的关系,进行多因素Logistic回归分析确定急性脑梗死的危险因素,利用ROC曲线评估患者血浆Lp-PLA2、hs-CRP和FIB水平对急性脑梗死的诊断价值。结果重度脑梗死患者的Lp-PLA2、hs-CRP和FIB水平均高于轻度及中度脑梗死患者(P<0.05);与对照组比较,脑梗组患者的血浆Lp-PLA2、hs-CRP和FIB水平均显著升高,差异均具有统计学意义(P<0.05)。血浆Lp-PLA2、hs-CRP和FIB水平与急性脑梗死发病风险显著相关(P<0.05)。Lp-PLA2、hs-CRP和FIB 3个指标中,Lp-PLA2的ROC曲线下面积最大,诊断价值最高;Lp-PLA2、hs-CRP和FIB联合检测能显著提高急性脑梗死的诊断效率。结论联合检测Lp-PLA2、hs-CRP和FIB对判断ACI患者神经功能缺损程度具有较高价值。

Lp-PLA2 LP(a)ApoB/ApoA-1水平与急性脑梗死严重程度及预后的相关性分析

目的:探究脂蛋白相关磷脂酶A2(Lp-PLA2)、脂蛋白a[LP(a)]、载脂蛋白B(ApoB/)/载脂蛋白A-1(ApoA-1)的表达水平与急性脑梗死(ACI)的严重程度和预后的相关性。方法:选择我院2022年1月至2023年1月收治的ACI患者122例作为病例组,根据疾病严重程度分为轻度组(54例)、中度组(49例)、重度组(19例),另选择同期体检健康者作为对照组(97例)。根据预后效果分为预后良好组(88例)和预后不良组(34例)。比较病例组和对照组患者的基本资料和生化指标的差异性,分析Lp-PLA2、LP(a)、ApoB/ApoA-1的表达水平对患者病情严重程度和预后效果影响。结果:病例组患者年龄、吸烟史、高血压例数、收缩压、LDL-C、LP(a)、Lp-PLA2指标高于对照组(P<0.05),HDL-C指标低于对照组(P<0.05),多因素Logistic回归分析结果,年龄、吸烟史、高血压、收缩压、HDLC、LDLC、LPa、LpPLA2、ApoB/ApoA-1是影响ACI发生的独立危险因素(P<0.05)。重度组患者Lp-PLA2、LP(a)、ApoB/ApoA-1指标显著高于轻度组和中度组(P<0.05),中度组Lp-PLA2、LP(a)、ApoB/ApoA-1指标显著高于轻度组(P<0.05),Spearman相关性比较,Lp-PLA2、LP(a)、ApoB/ApoA-1指标与患者病情严重程度呈正相关(r=0.796、0.718、0.451,P<0.05)。预后良好组患者Lp-PLA2、LP(a)、ApoB/ApoA-1指标显著高于预后不良组(P<0.05),ROC曲线分析结果显示,联合预测AUC为0.987。结论:高龄、血压血脂异常、生活习惯较差者更易患ACI,而Lp-PLA2、ApoB/ApoA-1水平与ACI的严重程度和预后效果呈明显的相关性,通过检测可有效评估患者病情发展,具有较高临床价值。

脂蛋白(a)与高龄慢性心力衰竭急性失代偿患者的预后相关性研究

目的 分析脂蛋白(a)[Lp(a)]与年龄≥80岁慢性心力衰竭(CHF)患者不良预后之间的关系,以及高龄CHF患者不良预后的影响因素。方法 收集2018年6月至2021年8月天津大学胸科医院心脏重症病房收治的高龄CHF急性失代偿患者135例,根据血清Lp(a)水平,分为高Lp(a)组[Lp(a)≥300 mg/L]73例和低Lp(a)组[Lp(a)<300 mg/L]62例,收集所有入组患者基线临床资料、12个月内随访结果,主要终点事件为因心力衰竭再住院和(或)全因死亡的复合终点。采用Kaplan-Meier生存曲线比较2组生存情况,采用logistic回归分析高龄CHF患者1年内发生终点事件的危险因素。结果 高Lp(a)组慢性肾脏病比例,同型半胱氨酸、TC及LDL-C水平高于低Lp(a)组,差异有统计学意义(P<0.05)。Kaplan-Meier生存分析显示,低Lp(a)组1年内无主要终点事件平均生存时间长于高Lp(a)组[9.8个月(95%CI:8.884~10.665)vs 8.2个月(95%CI:7.057~9.272),P<0.05]。多因素logistic回归分析显示,Lp(a)≥300 mg/L(OR=2.841,95%CI:1.133~7.092,P=0.026)、女性(OR=2.809,95%CI:1.111~7.092,P=0.029)、使用利尿剂(OR=4.631,95%CI:1.103~19.443,P=0.036)是患者1年内发生主要终点事件的独立危险因素。结论 Lp(a)≥300 mg/L是高龄CHF患者1年内发生因心力衰竭再住院和(或)全因死亡的独立危险因素。

老年高血压患者载脂蛋白A-Ⅰ与颈动脉粥样硬化的相关性分析

目的探讨老年高血压患者载脂蛋白A-Ⅰ与颈动脉粥样硬化的相关性,为老年高血压患者的危险因素进行早期干预提供参考依据。方法回顾性分析2022年4月至2023年4月于呼和浩特市第一医院门诊及住院治疗的老年高血压合并颈动脉粥样硬化患者的临床资料,将其作为观察组,另收集同期门诊及住院高血压患者的资料作为对照组。所有研究对象均进行血清载脂蛋白A-Ⅰ及颈血管彩超的检测。比较上述指标的变化情况,并分析老年高血压患者载脂蛋白A-Ⅰ与颈动脉粥样硬化的相关性。结果观察组研究对象载脂蛋白A-Ⅰ水平低于对照组,颈动脉血管彩超检查,观察颈内动脉、颈外动脉、颈总动脉的最大流速(V max)、最小流速(V min)、阻力指数RI、管径、内中膜厚度、斑块的大小、颈动脉狭窄差异均有统计学意义(P<0.05)。结论老年高血压患者载脂蛋白A-Ⅰ水平越低,颈动脉粥样硬化程度水平越高,且载脂蛋白A-Ⅰ与颈血管血流、颈动脉狭窄水平呈显著正相关。临床可应用载脂蛋白A-Ⅰ水平控制作为老年高血压合并颈动脉粥样硬化患者的早期干预指标,有助于延缓老年高血压患者颈动脉粥样硬化的发生,从而降低心脑血管病的发生率、致残率。

苍柴调中方辅助改善肝郁脾虚型肥胖2型糖尿病的疗效及对胰岛素抵抗、FFA、LDL-C水平的影响

目的:探讨苍柴调中方辅助改善肝郁脾虚型肥胖2型糖尿病(T2DM)的疗效,并分析其对胰岛素抵抗、游离脂肪酸(FFA)、低密度脂蛋白胆固醇(LDL-C)水平的影响。方法:选取2020年4月至2023年4月该院收治的肝郁脾虚型肥胖T2DM患者100例,根据随机数字表法分为两组,各50例。对照组患者使用二甲双胍治疗,观察组患者在对照组基础上联合苍柴调中方辅助治疗。观察两组患者的治疗效果,比较两组患者治疗前后中医症状积分、糖代谢指标[空腹血糖(FBG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)]、血清FFA、LDL-C、肿瘤坏死因子α(TNF-α)水平的差异,并对不良反应发生率进行统计。结果:观察组患者的治疗总有效率高于对照组,不良反应发生率低于对照组,差异均有统计学意义(P<0.05)。治疗后,观察组患者倦怠乏力、精神抑郁、脘腹闷胀及大便黏滞等中医症状积分均低于对照组,差异均有统计学意义(P<0.05)。与治疗前比较,两组患者治疗后的FBG、HOMA-IR、FINS水平均明显降低,其中观察组患者治疗后的FINS、FBG及HOMA-IR水平低于对照组,差异均有统计学意义(P<0.05)。观察组患者治疗后的血清LDL-C、FFA、TNF-α水平均低于对照组,差异均有统计学意义(P<0.05)。结论:苍柴调中方辅助治疗可明显提高肝郁脾虚型肥胖T2DM患者的治疗效果,改善胰岛素抵抗,下调血清FFA、LDL-C水平。

Lp-PLA2基因多态性与颈动脉斑块组织病理染色结果的相关性

目的探讨脂蛋白相关磷脂酶A2(Lp-PLA2)基因多态性与颈动脉斑块组织病理染色结果的相关性。方法选取2021年1月—2023年10月在延安大学附属医院行颈动脉剥脱术的患者135例。收集所有患者的临床资料和药物使用情况,并检测血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、同型半胱氨酸(Hcy)、脂蛋白(a)[Lp(a)]、高敏C反应蛋白(hs-CRP)、Lp-PLA2水平和Lp-PLA2基因R92H、V297F、A379V位点多态性。对剥脱的颈动脉斑块组织行Von kossa染色、α-SMA染色、油红O染色、EVG染色、CD68+免疫组化染色。根据Lp-PLA2基因多态性检测结果,将所有患者分为对照组(R92H、A379V、V297F位点均未发生突变)、A379V组(仅A379V位点发生突变)、V297F组(仅V297F位点发生突变)、R92H组(仅R92H位点发生突变)。采用Spearman相关分析评估斑块组织不同病理染色结果之间的相关性。采用Logistic回归分析评估Lp-PLA2基因多态性对斑块组织病理染色结果的影响。结果对照组、A379V组、V297F组和R92H组之间年龄和血清HDL-C、LDL-C、Lp-PLA2水平差异均有统计学意义(P<0.05),其他指标4个组之间差异均无统计学意义(P>0.05)。对照组、A379V组、V297F组、R92H组斑块组织内钙化和坏死核、脂肪、弹力纤维胶原纤维和巨噬细胞阳性百分比差异均有统计学意义(P<0.05)。4个组之间平滑肌细胞阳性百分比差异无统计学意义(P>0.05)。R92H组斑块组织Von kossa染色结果与CD68+免疫组化染色结果呈正相关(r=0.819,P=0.025),其他病理染色结果之间均无相关性(P>0.05)。对照组、A379V组和V297F组斑块组织不同病理染色结果之间均无相关性(P>0.05)。调整年龄和血清HDL-C、LDL-C、Lp-PLA2后,Lp-PLA2基因R92H位点突变是斑块组织内钙化和坏死核阳性百分比、巨噬细胞阳性百分比升高的独立危险因素[比值比(OR)值分别为1.97、1.26,95%可信区间(CI)为1.56~2.19、1.06~1.53,P<0.05]。结论Lp-PLA2基因R92H位点突变会影响颈动脉斑块的稳定性,增加斑块破裂的风险,临床应重点关注LpPLA2基因R92H位点突变人群。

不稳定型心绞痛患者血清RBP-4、Lp-PLA2水平及依折麦布治疗影响研究

目的探究不稳定型心绞痛(UA)患者血清视黄醇结合蛋白-4(RBP-4)、脂蛋白相关磷脂酶A2(Lp-PLA2)水平及依折麦布治疗影响。方法选取2021年1月至2023年1月于唐山市人民医院心内科确诊的UA患者84例为研究对象,其中男性48例,女性36例;根据冠状动脉病变程度分为:Gensini评分<20分为轻度组(27例)、20分≤Gensini评分<40分为中度组(36例)和Gensini评分≥40分为重度组(21例);按随机数字表法分为观察组和对照组,每组各42例。所有患者均行常规治疗,对照组在此基础上给予瑞舒伐他汀治疗,观察组给予瑞舒伐他汀+依折麦布治疗,两组患者均连续治疗6个月。比较不同冠状动脉病变程度组RBP-4、Lp-PLA2水平;比较治疗后观察组和对照组脂代谢、RBP-4、Lp-PLA2水平以及不良心血管事件的发生情况。结果①血清RBP-4、Lp-PLA2水平为:轻度组<中度组<重度组,差异有统计学意义(P<0.05)。斯皮尔曼等级相关分析显示,血清RBP-4、Lp-PLA2水平与UA患者冠状动脉病变程度呈正相关(r=0.844、r=0.729,P<0.05)。②重复测量方差分析显示,血脂水平时点、组间、交互比较差异有统计学意义(P<0.05)。治疗前,两组总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、三酰甘油(TG)水平的比较,差异无统计学意义(P>0.05);治疗3个月、6个月,两组TC、TG、LDL-C的水平均降低(P<0.05),而HDL-C升高(P<0.05),且观察组TC、TG、LDL-C水平低于对照组,HDL-C水平高于对照组,差异有统计学意义(P<0.05)。③重复测量方差分析显示,RBP-4、Lp-PLA2水平时点、组间、交互比较,差异有统计学意义(P<0.05)。治疗前,两组RBP-4、Lp-PLA2水平比较,差异无统计学意义(P>0.05);治疗3个月、6个月,两组RBP-4、Lp-PLA2水平均降低(P<0.05),且观察组RBP-4、Lp-PLA2水平低于对照组,差异有统计学意义(P<0.05)。④观察组心血管事件发生率(7.14%)低于对照组(23.81%),差异有统计学意义(P<0.05)。结论UA患者血清RBP-4、Lp-PLA2水平与冠状动脉病变程度相关,依折麦布可改善不稳定型心绞痛患者的脂代谢水平,调节血清RBP-4、Lp-PLA2水平,减少心血管事件发生。

脂蛋白a在冠心病合并糖尿病中的意义

相关研究证实高血浆脂蛋白a[Lp(a)]水平与动脉粥样硬化性心血管疾病和钙化性主动脉瓣狭窄存在潜在的因果关系。在糖尿病患者中,Lp(a)升高与首次心血管疾病风险增加密切相关。更多的证据表明,降低传统危险因素后,Lp(a)水平升高仍与残留的心血管风险相关。冠心病和糖尿病同属于代谢性疾病,冠心病合并糖尿病(心糖共病)患者较冠心病患者心血管事件发生率高5~6倍。本文针对脂蛋白a的结构、功能及与心糖共病的关系研究进展进行综述。

急性脑梗死患者不同性质颈动脉粥样斑块及预后的sdLDL-C、Lp-PLA2水平观察

目的 观察急性脑梗死(ACI)患者的小而密低密度脂蛋白胆固醇(sdLDL-C)、脂蛋白相关磷脂酶A2(Lp-PLA2)水平,探讨其与颈动脉粥样斑块稳定性的关系,以期为早期识别和改善患者预后提供思路。方法 依据颈部血管超声检查粥样斑块性质结果,164例急性脑梗死患者(观察组)中无粥样斑块者49例、稳定粥样斑块者58例、不稳定粥样斑块者57例,以47例健康体检者为对照,比较2组的同型半胱氨酸(Hcy)、sdLDL-C、Lp-PLA2表达水平。统计患者入院时的美国国立卫生院卒中量表(NIHSS)得分,随访患者发病30 d的预后情况,并分析影响ACI预后的相关因素。结果 脑梗死患者的空腹血糖、甘油三酯、sdLDL-C/LDL-C、sdLDL-C/TC、Lp-PLA2水平均高于对照组,HDL-C水平低于对照组;有粥样斑块者的Hcy、sdLDL-C水平高于无粥样斑块者及对照组;不稳定粥样斑块者的TC、LDL-C水平高于无粥样斑块者及对照组,差异均有统计学意义(P<0.05)。预后不良组的不稳定粥样斑块发现率(45.78%)高于预后良好组(23.46%),入院时NIHSS评分及血糖、sdLDL-C、sdLDL-C/LDL-C、sdLDL-C/TC、Lp-PLA2水平均高于预后良好组,差异均有统计学意义(P<0.05)。结论 sdLDL-C、Lp-PLA2水平与急性脑梗死患者颈动脉粥样斑块的稳定性密切相关,对预后判断有积极意义。

Lipoprotein(a)and Benefit of PCSK9 Inhibition in Emergency Complex Higher-risk and Indicated Patients

Objective There is a large population of patients classified as complex higher-risk and indicated patients(CHIPs)in China with a poor prognosis.The treatment of these patients is complex and challenging,especially when acute cardiac events occur,such as acute coronary syndrome(ACS)or heart failure.Pharmacotherapy and some mechanical circulatory support(MCS)therapeutic devices can provide stable hemodynamic support for CHIPs-percutaneous coronary intervention(PCI).LDL-C is an important pathogenic factor in atherosclerosis,and the target of blood lipid control.Recent studies have revealed that lipoprotein(a)[Lp(a)],which is formed when a covalent bond between apolipoprotein(a)and apolipoprotein B-100 is made,produces an LDL-like particle.This particle is an independent risk factor for the development of atherosclerosis,and is closely correlated to stent thrombosis and restenosis.Furthermore,this requires active intervention.PCSK9 inhibitors have been used in lipid-lowering treatment,and preventing atherosclerosis.The present study explores the efficacy of PCSK9 inhibitors in CHIPs-ACS,and the association between the change in Lp(a)and survival after 2 years of follow-up.Methods The present real-world,prospective control study enrolled 321 CHIPs-ACS who underwent emergency PCI from August 2019 to November 2020,and these patients were followed up for 2 years.These patients were divided into two groups:PCSK9 group(n=161)given the combined PCSK9 inhibitor(140 mg of evolocumab every 2 weeks)and statins-based therapy,and SOC group(n=160)treated with statin-based lipid-lowering therapy alone.Then,the change in lipid index was measured,and the cardiovascular(CV)event recurrence rate was evaluated after one month and 2 years.Afterwards,the contribution of serum lipid parameters,especially the Lp(a)alteration,in patients with earlier initiation of the PCSK9 inhibitor to the CV outcome was analyzed.Results The LDL-C level was significantly reduced in both groups:52.3%in the PCSK9 group and 32.3%(P<0.001)in the SOC group.It is noteworthy that the Lp(a)level decreased by 13.2%in the PCSK9 group,but increased by 30.3%in the SOC group(P<0.001).Furthermore,the number of CV events was not significantly different between the PCSK9 and SOC groups after the 2-year follow-up period.In the PCSK9 group,the Lp(a)reduction was associated with the baseline Lp(a)levels of the patients(r2=−0.315,P<0.001).Moreover,the decrease in Lp(a)contributed to the decline in CV events in patients who received ACS CHIPs-PCI,and the decrease in Lp(a)level was independent of the LDL-C level reduction.Conclusion The early initiation of PCSK9 inhibitors can significantly reduce the LDL-C and Lp(a)levels in ACS CHIPs-PCI.However,further studies are needed to confirm whether PCSK9 inhibitors can reduce the incidence of CV disease in CHIPs.

中性粒细胞与淋巴细胞比值联合磷脂酶A2可迅速筛选急诊后循环缺血性卒中的高危人群

目的:分析中性粒细胞与淋巴细胞比值(NLR)联合脂蛋白相关磷脂酶A2(Lp-PLA2)对急诊以单纯头晕为主诉的患者发生后循环缺血性卒中的预测价值。方法:回顾性分析急诊科收治的以单纯头晕为主诉的408例患者的临床资料,按是否发生急性后循环脑梗死分为脑梗死组(117例)和非脑梗死组(291例),比较2组的基本资料和急诊入院资料,采用多因素logistic回归分析发生后循环缺血性卒中的独立危险因素,并应用受试者工作特征(ROC)曲线评估NLR联合Lp-PLA2对急诊单纯头晕患者发生后循环缺血性卒中的预测价值。结果:2组年龄、高血压及糖尿病史、吸烟史方面比较,差异有统计学意义(P均<0.05)。多因素Logistic回归分析显示,年龄、高血压及糖尿病史、NLR、Lp-PLA2是急诊单纯头晕患者新发后循环缺血性卒中的独立危险因素。NLR预测单纯头晕患者发生后循环缺血性脑卒中的ROC曲线下面积(AUC)为0.810(95%CI 0.763~0.856,P<0.05),最佳截断值为2.87,敏感度为0.812,特异性为0.732。Lp-PLA2预测单纯头晕患者发生后循环缺血性脑卒中的AUC为0.840(95%CI 0.797~0.884,P<0.05),最佳截断值为203.5 ng/mL,敏感度为0.761,特异性为0.804。NLR联合Lp-PLA2预测单纯头晕患者发生后循环缺血性脑卒中的AUC为0.851(95%CI 0.808~0.894,P<0.05),最佳截断值为0.620,敏感度为0.829,特异性为0.794。结论:NLR联合Lp-PLA2能迅速筛选出单纯头晕为主诉的患者中发生后循环缺血性卒中的高危人群,从而进行积极的血管评估及急诊头颅磁共振来避免漏诊,特别是高龄、合并高血压、糖尿病的患者。

血清CTRP3、Lp-PLA2、Gal-3水平在原发性高血压继发冠心病患者中的变化及临床意义

目的探讨血清C1q/肿瘤坏死因子相关蛋白3(CTRP3)、脂蛋白相关磷脂酶A2(Lp-PLA2)、半乳糖凝聚素-3(Gal-3)在原发性高血压继发冠心病患者中的变化及临床意义。方法选取该院2021年2月至2023年2月收治的186例原发性高血压患者为研究对象。根据患者是否合并冠心病,分为单纯高血压组67例、高血压合并冠心病组119例。比较两组入院时总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),以及血清CTRP3、Lp-PLA2、Gal-3水平,分析入院时血清CTRP3、Lp-PLA2、Gal-3水平与TC、TG、HDL-C、LDL-C以及继发冠心病的相关性。采用受试者工作特征(ROC)曲线分析血清CTRP3、Lp-PLA2、Gal-3联合检测对原发性高血压继发冠心病风险的预测效能。结果两组TC、TG、HDL-C、LDL-C、CTRP3、Lp-PLA2、Gal-3水平比较,差异均有统计学意义(P<0.05);入院时血清CTRP3水平与TC、TG、LDL-C水平以及继发冠心病均呈负相关(P<0.05),与HDL-C水平呈正相关(P<0.05);入院时血清Lp-PLA2、Gal-3水平与TC、TG、LDL-C水平以及继发冠心病均呈正相关(P<0.05),与HDL-C水平呈负相关(P<0.05);入院时血清CTRP3、Lp-PLA2、Gal-3联合检测预测原发性高血压继发冠心病的曲线下面积为0.924,灵敏度、特异度分别为84.03%、86.57%。结论原发性高血压患者继发冠心病的风险与血清CTRP3、Lp-PLA2、Gal-3水平密切相关,CTRP3、Lp-PLA2、Gal-3可作为原发性高血压患者冠心病早期预防、诊断提供参考依据。