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.

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.

Relationships between serum lipid,lipoprotein,triglyceride-rich lipoprotein,and high-density lipoprotein particle concentrations in post-renal transplant patients

Objective:Disturbances in lipid and lipoprotein profiles in patients after kidney transplantation (Tx) are still not understood. Methods:Serum levels of lipids,lipoprotein,triglyceride-rich lipoproteins (TRLs),and high-density lipoprotein (HDL) particles were determined,lipid and lipoprotein ratios were calculated,and their relationships in Tx patients with hypertriglyceridemia (HTG) and lower apolipoprotein AI (apoAI) concentration were examined. Serum lipid and lipoprotein levels were measured in 109 Tx patients and 89 healthy subjects. HDL particle levels were de-termined by enzyme-linked immunosorbent assay (ELISA). Results:Tx patients had disturbed concentration,com-position,and metabolism of TRLs and HDL particles. Multivariance analysis showed significant and positive correlation between HDL cholesterol/apoAI (HDL-C/apoAI) and HDL-C/HDL ratios,which indicates that both ratios could sensi-tively reflect changes in the HDL subclasses and their distribution into smaller size particles. In Tx patients,the de-creased HDL-C/apoAI ratio indicates that,along with the decreased apoAI concentration,the HDL-C level is de-creased. However,a low HDL-C/HDL ratio indicates that HDL particles in Tx patients transport lesser content of HDL-C but more triglyceride (TG) (high TG/HDL ratio),and thus are hypercatabolized and removed; therefore,con-centration of HDL particles in serum was decreased. Conclusion:The decrease of HDL-C/apoAI ratio seems to be a good marker of HDL subclass distribution into smaller size particles.

Carbamylated lipoproteins in diabetes

Diabetic dyslipidemia is characterized by quantitative and qualitative abnormalities in lipoproteins.In addition to glycation and oxidation,carbamylation is also a post-translational modification affecting lipoproteins in diabetes.Patients with type 2 diabetes(T2D)exhibit higher levels of carbamylated low-density lipoproteins(cLDL)and high-density lipoproteins(cHDL).Accumulating evidence suggests that cLDL plays a role in atherosclerosis in diabetes.cLDL levels have been shown to predict cardiovascular events and all-cause mortality.cLDL facilitates immune cell recruitment in the vascular wall,promotes accumulation of lipids in macrophages,and contributes to endothelial dysf-unction,endothelial nitric oxide-synthase(eNOS)inactivation and endothelial repair defects.Lastly,cLDL induces thrombus formation and platelet aggregation.On the other hand,recent data have demonstrated that cHDL serum level is independently associated with all-cause and cardiovascular-related mortality in T2D patients.This relationship may be causative since the atheroprotective properties of HDL are altered after carbamylation.Thus,cHDL loses the ability to remove cholesterol from macrophages,to inhibit monocyte adhesion and recruitment,to induce eNOS activation and to inhibit apoptosis.Taken together,it seems very likely that the abnormalities in the biological functions of LDL and HDL after carbamylation contribute to atherosclerosis and to the elevated cardiovascular risk in diabetes.

Nanotechnologies meeting natural sources:Engineered lipoproteins for precise brain disease theranostics

Biological nanotechnologies have provided considerable opportunities in the management of malignancies with delicate design and negligible toxicity,from preventive and diagnostic to therapeutic fields.Lipoproteins,because of their inherent blood-brain barrier permeability and lesion-homing capability,have been identified as promising strategies for high-performance theranostics of brain diseases.However,the application of natural lipoproteins remains limited owing to insufficient accumulation and complex purification processes,which can be critical for individual therapeutics and clinical translation.To address these issues,lipoprotein-inspired nano drug-delivery systems(nano-DDSs),which have been learned from nature,have been fabricated to achieve synergistic drug delivery involving site-specific accumulation and tractable preparation with versatile physicochemical functions.In this review,the barriers in brain disease treatment,advantages of state-of-the-art lipoprotein-inspired nano-DDSs,and bio-interactions of such nano-DDSs are highlighted.Furthermore,the characteristics and advanced applications of natural lipoproteins and tailor-made lipoprotein-inspired nano-DDSs are summarized.Specifically,the key designs and current applications of lipoprotein-inspired nano-DDSs in the field of brain disease therapy are intensively discussed.Finally,the current challenges and future perspectives in the field of lipoprotein-inspired nano-DDSs combined with other vehicles,such as exosomes,cell membranes,and bacteria,are discussed.

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.

Comparison of the effects of 3 kinds of oils rich in omega-3 polyunsaturated fatty acids on glycolipid metabolism and lipoprotein subfractions

Dietary omega-3 polyunsaturated fatty acids(ω-3 PUFAs)can be classifi ed into animal-and plant-derivedω-3 PUFAs.Patients with type 2 diabetes(T2DM)are frequently accompanied by dyslipidemia,which is closely related to the high-density lipoprotein(HDL-C)subfractions change.This study aimed to determine the effects of different sourcesω-3 PUFAs on glucolipid metabolism and lipoprotein subfractions in T2DM with dyslipidemia.Ninety T2DM patients with dyslipidemia were randomly assigned to take 3 g/day fi sh oil(FO,containing eicosapentaenoic acid(EPA)and docosahexaenoic acid(DHA)),3 g/day perilla oil(PO,containingα-linolenic acid(ALA)),or 3 g/day blend oil(BO,containing EPA,DHA and ALA)for 3 months.90 patients completed the intervention.There was a significant reduction of glycated hemoglobin(HbA1c)in all the groups.The triglycerides(TG)in the FO group were signifi cantly different with a group×time interaction(P=0.043),which was higher compared with the other two groups.The serum small HDL-C subfractions in the PO group was higher and the serum large HDL-C subfractions in the PO group was lower than those in the BO and FO groups.Plant-derivedω-3 PUFAs are more effective at controlling blood glucose than animal-derivedω-3 PUFAs.However,animal-derivedω-3 PUFAs have a signifi cant lowering effect on TG compared with plant-derivedω-3 PUFAs.Particularly,large HDL-C subfractions after animal-derivedω-3 PUFAs intake were higher than plant-derivedω-3 PUFAs intake;while small HDL-C subfractions were lower.Both the animal-and plant-derivedω-3 PUFAs have practical value in improving glucose and lipids metabolism in T2DM patients with dyslipidemia.

Lipoprotein (a) Cut-Off in Chronic Kidney Disease Patients with a History of Cardiovascular Disease in Center Hospital University Souro SANOU, Burkina Faso

Patients living with chronic kidney disease (CKD) are at high risk of cardiovascular events. Our aim in this study was to assess the cut-off value for lipoprotein (a) (Lp(a)) in CKD patients with a history of cardiovascular disease (CVD). This was a cross-sectional study. Variables including age, sex, history of CVD, body mass index and CKD stage, were collected during CKD patient’s first admission in the nephrology dialysis department. Blood samples were collected for quantitative determination of Lp(a) by immunoturbidimetric method. They were divided into two groups: CKD patients without history of CVD and CKD patients with history of CVD. Fisher’s exact test was used to assess associations with a significance level of 0.05%. Area under the curve (AUC) and new cut-off value for Lp(a) were identified by drawing Receiver Operating Characteristic (ROC) curve. A total of seventy CKD patients with median age of 43 years [minimum-maximum = 15 - 78 years] were included. Patients with history of CVD were 65.71% (46/70). New Lp(a) cut-off point in CKD patients with history of CVD was 66.50 nmol/L [sensitivity, 87.00%;specificity, 58.30%;AUC = 0.727;p = 0.000]. ROC curve demonstrated good performance of Lp(a) to screen CKD patients with history of CVD. Further research is needed to determine an LPA gene polymorphism’s contribution to increasing risk for CVD at each kidney disease stage.

Diagnostic and prognostic implications of non-high-density lipoprotein cholesterol and homocysteine levels for cognitive impairment in thalamic infarction

BACKGROUND Patients with thalamic infarction experience abnormal blockages of multinuc-leated vessels,affecting the body and thereby the thalamus.Most patients with thalamic infarction have an adverse prognosis,which seriously affects their safety.Therefore,it is essential to analyze the independent risk factors that influence the prognosis of patients with thalamic infarction and develop corresponding preventive measures.AIM To explore the effect of non-high-density lipoprotein cholesterol(non-HDL-C)and Homocysteine(Hcy)levels in cognitive impairment in thalamic infarction.METHODS From March 2019 to March 2022,80 patients with thalamic infarction were divided into a group with cognitive impairment[Montreal Cognitive Assessment(MoCA)score<26;35 patients]and a group with normal cognitive function(MoCA score of 26-30;45 patients)according to the MoCA score.In addition,50 healthy people in the same period were selected as the control group.A correlation between the non-HDL-C and Hcy levels and the MoCA score and receiver operating characteristic curve was observed,and the serum non-HDL-C and Hcy levels were analyzed for the diagnosis of cognitive impairment in patients with thalamic infarction.According to the Modified Rankin Scale(MRS)score,80 patients with thalamic infarction were divided into a good prognosis group(MRS score≤2)and a poor prognosis group(MRS score>2).RESULTS The non-HDL-C and Hcy levels were significantly higher in the group with cognitive impairment than in the group with normal cognitive function(P<0.05).There was no significant difference in the non-HDL-C level between the control group and the group with normal cognitive function(P>0.05).The MoCA scores of the group with cognitive impairment were significantly lower than those of the group with normal cognitive function and the control group(P<0.05).There was a significant difference between the control group and the group with normal cognitive function(P<0.05).The non-HDL-C and Hcy levels were correlated with the MoCA score(P<0.05),cognitive impairment[areas under the curve(AUC)=0.709,95%confidence interval(95%CI):0.599-0.816],the non-HDL-C level,and could predict cognitive impairment in patients with thalamic infarction(AUC=0.738,95%CI:0.618-0.859).Hcy combined with non-HDL-C levels can predict cognitive impairment in patients with thalamic infarction(AUC=0.769,95%CI:0.721-0.895).RESULTS There were 50 patients in the good prognosis group and 30 patients in the poor prognosis group.Compared with the good prognosis group,in the poor prognosis group,the National Institutes of Health Stroke Scale(NIHSS)score,non-HDL-C level,Hcy level,large-area cerebral infarction,atrial fibrillation,and activated partial prothrombin time were statistically significant(P<0.05).The non-HDL-C level,the Hcy level,the NIHSS score,extensive cerebral serum,and atrial fibrillation may all be independent risk factors for poor prognosis in patients with thalamic infarction(P<0.05).CONCLUSION Non-HDL-C and Hcy levels are positively correlated with cognitive impairment in patients with thalamic infarction.Non-HDL-C and Hcy levels can be used in the diagnosis of cognitive impairment in patients with thalamic infarction,and the combined detection effect is better.The main factors affecting the prognosis of patients with thalamic infarction are the non-HDL-C level,the Hcy level,the NIHSS score,large-area cerebral infarction,and atrial fibrillation.Clinically,corresponding preventive measures can be formulated based on the above factors to prevent poor prognosis and reduce mortality.

老年女性髋部脆性骨折患者骨转换特征及其与血清高密度脂蛋白胆固醇的相关性

目的探讨骨转换与老年女性髋部脆性骨折(fragile hip fracture,HF)风险及与高密度脂蛋白胆固醇(HDLc)的相关性。方法选取2021年1月至2022年12月年龄≥60岁女性住院骨质疏松症患者共661例,分为无骨折组(A组)266例和HF组(B组)395例。检测总胆固醇(Tch)、甘油三酯(TG)、HDLc、低密度脂蛋白胆固醇(LDLc)、骨钙素N段中分子片段(N-MID OC)、Ⅰ型胶原羧基端肽β特殊序列(β-CTX)、总蛋白(TP)、白蛋白(Alb)、钙(Ca)、磷(P)、镁(Mg)、尿素(Urea)、肌酐(Cr)、胱抑素C(Cys-C)、肾小球滤过率(eGFR)、骨形成率(MoMF)、骨吸收率(MoMR)及骨转化率(MoT)。结果(1)HF组TP[118(108,128)vs 124(114,131)]、Alb[38.4±3.7 vs 40.0±4.3]、HDLc[1.51(1.24,1.71)vs 1.54(1.37,1.73)]、Ca[2.21±0.12 vs 2.29±0.12]、P[1.03±0.16 vs 1.08±0.17]含量较无骨折组降低,年龄[76(68,83)vs 73(67,78)]、β-CTX[0.57(0.40,0.77)vs 0.34(0.19,0.56)]、MoMR[1.84(1.30,2.51)vs 1.09(0.61,1.83)]及MoT[2.16(1.56,2.85)vs 1.56(1.09,2.38)]较无骨折组增加,差异有统计学意义(P<0.05)。N-MID OC、MoMF、Urea、Cr、Cys-C、eGFR、Tch、TG、LDLc及Mg差异无统计学意义(P>0.05)。(2)老年女性HF与HDLc、TP、ALB、Ca、P、Mg呈负相关(r=-0.09、-0.26、-0.16、-0.28、-0.12、-0.03,P<0.05),与年龄、β-CTX、MoMR、MoT呈正相关(r=0.17、0.36、0.36、0.26,P<0.05),与N-MID OC、MoMF、Urea、Cr、Cys-C、eGFR、Tch、TG、LDLc无相关性(P>0.05)。(3)年龄、MoT、TP、Ca、P为老年女性HF的风险因素,OR分别为1.03(95%CI:1.01~1.06)、1.75(95%CI:1.44~2.12)、0.96(95%CI:0.92~0.99)、0.06(95%CI:0.01~0.37)、0.18(95%CI:0.06~0.6),P<0.05。(4)HDLc与骨转化间存在“U”型关系,P<0.01,其切点为1.692 mmol/L。结论高骨转换是老年女性HF的危险因素,其骨转化率与HDLc存在U型相关。

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。

阿魏酸钠治疗梅尼埃病模型小鼠的效果及机制研究

目的探讨阿魏酸钠治疗梅尼埃病(MD)模型小鼠的效果及机制。方法BALB/c小鼠采用后颅窝硬膜外入路内淋巴囊阻塞术联合腹腔注射醛固酮的方法构建MD模型,将造膜成功的60只小鼠随机分为模型组,阿魏酸钠低、中、高剂量组,地塞米松组,每组12只。另取12只BALB/c小鼠作为假手术组。分组鼓室给药后以听觉诱发脑干反应(ABR)检测各组小鼠听力水平。HE染色及磁共振成像(MRI)观测各组小鼠耳蜗形态及其膜迷路积水情况;酶联免疫吸附试验检测各组小鼠血清脂蛋白(a)[Lp(a)]及促炎因子白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)水平;免疫组织化学染色及Western blot法检测各组小鼠Lp(a)表达。结果与假手术组比较,模型组小鼠ABR阈值、膜迷路积水评分、中阶面积占比、血清Lp(a)、IL-6与TNF-α水平、耳蜗组织Lp(a)阳性表达的IOD值与Lp(a)蛋白表达增加(P<0.05);与模型组比较,阿魏酸钠低、中、高剂量组及地塞米松组小鼠ABR阈值、膜迷路积水评分、中阶面积占比、血清Lp(a)、IL-6与TNF-α水平、耳蜗组织Lp(a)阳性表达的IOD值与Lp(a)蛋白表达降低(P<0.05),且高剂量阿魏酸钠效果更明显。结论阿魏酸钠可下调Lp(a)蛋白表达,减少促炎因子产生,抑制炎症反应,进而减轻MD小鼠膜迷路积水症状,并改善其听觉功能。

基于ox-LDL/LOX-1信号通路探讨脂质代谢紊乱促进肺癌进展中的机制

目的基于氧化低密度脂蛋白(ox-LDL)/人凝集素样氧化低密度脂蛋白受体1(LOX-1)信号通路探讨脂质代谢紊乱促进肺癌进展的机制。方法收集81个已鉴定的具有成对相邻非癌组织(离肿瘤至少5 cm)的肺腺癌组织,使用免疫组织化学检测LOX-1表达。肺腺癌细胞系(A549、H1299细胞)中过表达LOX-1。用Transwell测定细胞侵袭能力。用不同浓度oxLDL处理细胞,并检测细胞中LOX-1表达情况。结果在包含原发性人肺癌和匹配的邻近非癌组织中,肿瘤中LOX-1染色比非癌组织样品明显增强(中值H分数99.4 vs.16.2,P<0.001)。高LOX-1表达与低生存显著相关(P<0.001)。与无淋巴结转移的患者相比,发生淋巴结转移患者的癌组织具有更高的LOX-1水平(中值H分数83.2 vs.121.1,P<0.01)。LOX-1过表达显著促进肺癌细胞的侵袭转移细胞数(P<0.01)。此外,LOX-1是ox-LDL诱导的肺癌细胞转移所必需的功能靶点。伊他替尼抑制LOX-1过表达的A549在体外的转移能力。结论LOX-1的表达随着oxLDL水平的升高而增加,并且LOX-1的表达上调促进了肺癌细胞的转移,其作用机制可能与激活Janus激酶/转录因子激活子(JAK1/STAT6)信号通路有关。

脊柱退变住院患者血清尿酸/高密度脂蛋白比值与骨密度的相关性

目的探索脊柱退变住院患者血清尿酸/高密度脂蛋白比值与骨密度的相关性。方法共纳入803例脊柱退变的受试者,评估临床因素及实验室检查结果,测量骨密度,按照骨密度结果分为骨质疏松症组及非骨质疏松症组。采用多元Logistic回归分析血清尿酸/高密度脂蛋白比值(uric acid to high-density lipoprotein cholesterol ratio,UHR)与骨质疏松症的相关性。结果与非骨质疏松症组相比,骨质疏松症组的UHR更低(244.93±.102.51 vs 199.97±.91.96,P<0.001),多元Logistics回归分析提示,在校正了骨质疏松症的传统危险因素后,UHR最高的四分位患者发生骨质疏松症的可能性是UHR最低的四分位患者的0.402倍(P=0.018)。骨质疏松症的患病率在UHR四分位呈下降的趋势,骨密度在UHR四分位呈升高的趋势。UHR在骨量正常、骨量减少及骨质疏松症3组呈下降的趋势。结论低UHR是昆山地区脊柱退变住院患者发生骨质疏松症的危险因素。对于UHR较低的脊柱退变患者,应注意筛查骨质疏松症。

基于两样本孟德尔随机化方法分析低密度脂蛋白胆固醇与哮喘的因果关系

目的以单核苷酸多态性(single nucleotide polymorphism,SNP)为工具变量,基于孟德尔随机化(Mendelian randomization,MR)法探究低密度脂蛋白胆固醇(LDL-C)与哮喘的因果关系。方法根据全基因组关联研究(GWAS)的基因数据,借助MR-base平台,获得2020年3月10日至2023年3月10日样本量最大的LDL-C及哮喘的GWAS数据,筛选出与LDL-C相关的SNP(筛选条件设定为P<5×10-8),通过逆方差加权分析法(IVW)、加权中位数法(WME)、加权模型、简单模型和MR-Egger法分析LDL-C与哮喘风险的关系,同时绘制SNP相关的LDL-C与哮喘风险的森林图及散点图。结果筛选出的301个SNP均与哮喘不存在基因多效性(MR-Egger回归截距0.007)。所有的回归结果均显示,LDL-C为哮喘的危险因素,MR-Egger回归OR=1.609(95%CI 1.228~2.107)、WME OR=1.448(95%CI 1.266~1.656)、IVW OR=1.499(95%CI 1.348~1.667)、加权模型OR=1.462(95%CI 1.212~1.763)、简单模型OR=1.374(95%CI 1.024~1.846)。MR-Egger回归结果显示统计量Q=1095.819(P<0.001),提示SNP间存在异质性,故选择随机效应IVW模型。结论LDL-C与哮喘之间存在因果关系,LDL-C水平越高,哮喘发病风险越大。

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。

血清氧化低密度脂蛋白与多囊卵巢综合征不孕患者临床妊娠结局的相关性研究

目的分析血清氧化低密度脂蛋白(ox-LDL)与多囊卵巢综合征(PCOS)不孕患者临床妊娠结局的关系。方法采用前瞻性队列研究方法连续收集2020年1月至2021年12月承德市中心医院诊治的155例PCOS不孕患者作为研究对象。记录患者的妊娠成功率,记录患者入组时临床资料及基线性激素指标、胰岛素抵抗相关指标、血清ox-LDL水平。根据血清ox-LDL水平分为高水平组(n=85)和低水平组(n=70)。分析血清ox-LDL与PCOS不孕患者临床妊娠结局的相关性。结果155例PCOS不孕患者中有34例成功妊娠,临床妊娠率为21.94%。高水平组临床妊娠成功率低于低水平组,稳态模型胰岛素抵抗指数(HOMA-IR)高于低水平组,差异具有统计学意义(P<0.05)。Logistic回归分析显示,PCOS不孕患者血清ox-LDL、HOMA-IR和甘油三酯(TG)表达上调是导致PCOS不孕患者临床妊娠失败的危险因素(P<0.05)。Pearson相关性检验显示,血清ox-LDL水平与PCOS不孕患者HOMA-IR和TG呈正相关(r>0,P<0.05)。受试者工作特征(ROC)曲线显示,血清ox-LDL水平预测PCOS不孕患者临床妊娠结局的曲线下面积(AUC)为0.806;当血清ox-LDL临界值达498.09μg/L时,患者发生临床妊娠失败风险较高。结论PCOS不孕患者临床妊娠结局与血清ox-LDL升高有关,早期检测有助于预测临床妊娠失败的风险,其可作为辅助预测指标。

基于脂组学方法分析不同危险因素的脑卒中患者预后的研究

目的探讨基于脂组学方法分析不同危险因素的脑卒中患者预后的研究。方法回顾性分析九江市第一人民医院2021年2月至2023年2月收治的120例缺血性脑卒中(AIS)患者的临床资料治疗3个月后将其按预后情况分为良好组(n=82)和不良组(n=38)。分析患者年龄、性别、吸烟史、饮酒史、高血压、高脂血症、糖尿病、脑卒中家族遗传史、总胆固醇(TC)、三酰甘油(TG)、糖化血红蛋白(HbA1c)、低密度脂蛋白胆固醇(LDL-C)水平对AIS患者预后的影响。结果全部纳入研究的120例AIS患者中,有38例患者出现预后不良,发生率为31.67%;有82例预后良好,发生率为68.33%。单因素分析结果提示,两组性别、吸烟史、饮酒史、高血压、高脂血症、糖尿病、脑卒中家族遗传史比较,差异无统计学意义(P>0.05);两组患者年龄、TC、TG、HbA1c以及LDL-C比较,差异有统计学意义(P<0.05)。多因素分析结果提示,年龄(β=0.266,OR=1.304,95%CI=1.136~1.498)、HbA1c(β=0.838,OR=2.312,95%CI=1.269~4.212)、LDL-C(β=1.662,OR=5.269,95%CI=2.178~12.745)是AIS患者预后不良的危险因素(P<0.05)。结论年龄、HbA1c、LDL-C是AIS患者预后不良的危险因素。可根据上述因素进行针对性干预,以期减少AIS患者预后不良的发生率。

血清小而密低密度脂蛋白胆固醇和总抗氧化能力水平与脑梗死患者认知功能障碍的相关性分析

目的:探究脑梗死患者血清小而密低密度脂蛋白胆固醇(small dense low-density lipoprotein cholesterol, sdLDL-C)和总抗氧化能力(total antioxidant capacity, T-AOC)水平变化及其与认知功能障碍发生的关系。方法:选择148例脑梗死患者,依据发病后7 d是否出现认知功能障碍,分为非障碍组(n=77)和障碍组(n=71);分别采用过氧化氢酶法和比色法测定两组血清sdLDL-C和T-AOC水平,并进行比较;Pearson相关系数法分析脑梗死患者血清sdLDL-C、T-AOC水平与蒙特利尔认知评估(MoCA)评分相关性;二元Logistic回归分析影响脑梗死患者认知功能障碍发生的危险因素。结果:与非障碍组相比,障碍组血清sdLDL-C水平明显升高(P<0.05),T-AOC水平明显降低(P<0.05)。相关性分析显示,血清sdLDL-C水平与MoCA评分呈负相关(r=-0.516,P<0.05),T-AOC水平与MoCA评分呈正相关(r=0.446,P<0.05)。Logistic回归分析显示,高血压、糖尿病、病情严重程度、血清sdLDL-C和T-AOC是脑梗死患者认知功能障碍发生的独立影响因素(P<0.05)。结论:脑梗死患者血清sdLDL-C水平升高,T-AOC水平降低,二者是影响脑梗死患者并发认知功能障碍的独立影响因素。

总胆固醇与高密度脂蛋白胆固醇比值同肩袖撕裂的相关性

目的 探讨总胆固醇与高密度脂蛋白胆固醇比值同肩袖撕裂发生的相关性。方法 选取2018年1月至2023年6月期间在昆山市中医医院骨科住院行肩关节镜手术治疗的患者797例,其中男259例,女538例;年龄40~79岁,平均(58.86±8.73)岁。按照是否存在肩袖撕裂分为肩袖撕裂组559例及非肩袖撕裂组238例。收集患者基本信息及实验室检查结果,使用多因素Logistics回归分析探讨总胆固醇与高密度脂蛋白胆固醇比值同肩袖撕裂发生的相关性。结果 肩袖撕裂组的年龄、空腹血糖、中性粒细胞、总胆固醇与高密度脂蛋白比值高于非肩袖撕裂组。肩袖撕裂组的血红蛋白、高密度脂蛋白、血清镁及血清磷水平低于非肩袖撕裂组。多因素Logistic回归分析结果表明,总胆固醇与高密度脂蛋白比值同肩袖撕裂的发生有关。肩袖撕裂的患病率在总胆固醇与高密度脂蛋白比值四个四分位呈升高的趋势(21.65%、24.15%、25.76%及28.44%)。结论 血脂异常与肩袖撕裂具有相关性,总胆固醇与高密度脂蛋白比值越高,肩袖撕裂发生的风险越大。