New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival rate.Therefore,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing MIBC.Methods:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC.The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis.Western blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B expression.Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.Results:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC.Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels.Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression.Compared to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression.Conclusion:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition.This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

XbaⅠpolymorphisms of apolipoprotein B gene:Another risk factor of gallstone formation after radical gastrectomy

AIM:To prospectively investigate the association between the XbaⅠpolymorphisms of apolipoprotein B (APOB)gene and gallstone formation following gastrectomy.METHODS:The study was conducted between January 2005 and December 2006.A total of 186 gastric cancer patients who had undergone radical gastrectomy were grouped according to XbaⅠpolymorphisms of APOB gene(X+X-group,n=24 and X-X-group,n =162)and compared.The XbaⅠpolymorphisms of APOB gene were detected by polymerase chain reaction-restriction fragment length polymorphism(PCRRFLP).RESULTS:The incidence of gallstone was significantly higher in the X + X-group than in the X-X-group[54.2% vs 9.3%,RR=5.85(2.23-15.32),P<0.001].The serum levels of total cholesterol(TC)and low-density lipoprotein(LDL)were higher in the X + X-than in the X-X-group(4.02±1.12 vs 3.48±0.88,P=0.004 before surgery and 3.88±1.09 vs 3.40±0.86,P=0.008 after surgery).LDL was 2.21±0.96 vs 1.89±0.84(P =0.042)before surgery and 2.09±0.95 vs 1.72±0.85 (P=0.029)after surgery in the two groups.No relationship was found between XbaⅠpolymorphisms and gallbladder motility.CONCLUSION:In Chinese patients after radical gastrectomy,X + allele of APOB gene is another risk factor for the development of gallstone besides the gallbladder motility disorder after surgery.

C-reactive Protein Level,Apolipoprotein B-to-apolipoprotein A-1 Ratio,and Risks of Ischemic Stroke and Coronary Heart Disease among Inner Mongolians in China

Objective We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1（ApoB/ApoA-1） ratio on the incidence of ischemic stroke（IS） or coronary heart disease（CHD） in a Mongolian population in China.Methods From June 2003 to July 2012,2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation.All the participants were divided into four subgroups according to C-reactive protein（CRP） level and ApoB/ApoA-1 ratio.Cox proportional hazard models were used to estimate the hazard ratios（HRs） and 95% confidence intervals（CIs） for the IS and CHD events in all the subgroups.Results The HRs（95% CI） for IS and CHD were 1.33（0.84-2.12）,1.14（0.69-1.88）,and 1.91（1.17-3.11） in the ‘low CRP level with high ApoB/ApoA-1＇,‘high CRP level with low ApoB/ApoA-1＇,and ‘high CRP level with high ApoB/ApoA-1＇ subgroups,respectively,in comparison with the ‘low CRP level with low ApoB/ApoA-1＇ subgroup.The risks of IS and CHD events was highest in the ‘high CRP level with high ApoB/ApoA-1＇ subgroup,with statistical significance.Conclusion High CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population.This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population.

Apolipoprotein B100 quality control and the regulation of hepatic very low density lipoprotein secretion

Apolipoprotein B （apoB） is the main protein component of very low density lipoprotein （VLDL） and is necessary for the assembly and secretion of these triglyceride （TG）-rich particles. Following release from the liver, VLDL is converted to low density lipoprotein （LDL） in the plasma and increased production of VLDL can therefore play a detrimental role in cardiovascular disease. Increasing evidence has helped to establish VLDL assembly as a target for the treatment of dyslipidemias. Multiple factors are involved in the folding of the apoB protein and the formation of a secretion-competent VLDL particle. Failed VLDL assembly can initiate quality control mechanisms in the hepatocyte that target apoB for degradation. ApoB is a substrate for endoplasmic reticulum associated degradation （ERAD） by the ubiquitin proteasome system and for autophagy. Efficient targeting and disposal of apoB is a regu- lated process that modulates VLDL secretion and partitioning of TG. Emerging evidence suggests that significant overlap exists between these degradative pathways. For example, the insulin-mediated targeting of apoB to autop- hagy and postprandial activation of the unfolded protein response （UPR） may employ the same cellular machinery and regulatory cues. Changes in the quality control mechanisms for apoB impact hepatic physiology and pathology states, including insulin resistance and fatty liver. Insulin signaling, lipid metabolism and the hepatic UPR may impact VLDL production, particularly during the postprandial state. In this review we summarize our current understanding of VLDL assembly, apoB degradation, quality control mechanisms and the role of these processes in liver physiology and in pathologic states.

THE ASSOCIATION OF POLYMORPHISMS AT A VNTR LOCUS 3’TO THE APOLIPOPROTEIN B GENE WITH CORONARY HEART DISEASE IN CHINESE POPULATION

The polymorphisms of variable number of tandem repeats (VNTR) 3’to the apolipoprotein B (apo B) gene were investigated using polymerase chain reaction (PCR) in a sample of 103 patients with documented coronary heart disease (CHD) and 100 healthy individuals selected from Chinese Han nationality.Twelve segregating alleles (3’β29 -51) were observed in the pooled total of 203 subjects. The most common allele was 3’β 37. followed by 3’β39 with frequencies of 0. 362 and 0. 296, respectively. This model of allele distribution was coincident with the results form different ethnic groups, but the relative frequencies of alleles were different. In comparison with the allele frequencies between the patients and controls,alleles bigger than 3’β39 (3’VNTR-B) were significantly more common among the patients than among the controls (P<0. 001). Moreover. in the CHD group patients with plasma levels of TC≥3.88 mmol/L,LDL-C≥2. 59 mmol/L and HDL-C<l. 16mmol/L had significantly higher frequencies of 3’ VNTR-B allele (P<0. 01). Therefore,it is suggested that 3’ VNTR-B allele might be involved in the development of coronary atherosclerosis, presumably through their influences on lipid metabolism.This study supported by “8. 5” grant from Ministry of PublicHealth.

Apolipoprotein B Is a Good Tool for Screening Dyslipidaemia in Apparently Healthy Population

Dyslipidaemia is the major risk factor for cardiovascular disease (CVD) which is the leading cause of death in the world. Even though several lipid parameters are used, currently apolipoprotein B (apoB) is considered as the best predictor of CVD. Thus this study was carried out to find out the association between conventional lipid parameters and apoB in apparently healthy subjects. A descriptive cross-sectional study was carried out in 170 apparently healthy volunteers who were not diagnosed with dyslipidaemia. After 12 hours overnight fast venous blood was obtained and Total cholesterol (TC), Triglyceride (TG), High density lipoprotein cholesterol (HDL-C) were measured by enzymatic kit method. Low density lipoprotein cholesterol (LDL-C) was calculated by Friedewald formula and apoB was analyzed by immune turbid metry using a Konelab® auto analyzer. Among the participants, majority (63.5%) were females. The mean value of apoB concentration of the population was 103 ± 42 mg/dL which was similar and not significantly different between the genders (Males, 102 ± 37 mg/dL and Females, 104 ± 45 mg/dL). All lipid parameters showed a positive correlation with apoB concentration whereas HDL-C had a negative correlation (r = -0.165). HDL-C significantly (p < 0.05) decreased with increase in apoB concentration while LDL-C, TC/HDL-C and non-HDL-C significantly (p < 0.05) increased with an increase in apoB concentration. Present study suggests that serum apoB has better correlations and associations with the parameters that are used in conventional lipid profile and with markers recommended for diagnosing dyslipidaemia. Hence apoB could be used as a single marker for screening dyslipidaemia in apparently healthy people.

The Relationship between Apolipoprotein B Gene Loci Polymorphisms and Coronary Heart Disease.

The authors utilized the polymerase chain reaction to rapidly and accurately type a variable number of tandemly repeated loci (VNTR loci) of the 3’ flanking region of apolipoprotein B (apo B) gene, and studied the relationship between this loci polymorphisms and coronary heart disease (CAD); comparisons were made with relative diseases and

Apolipoprotein B/Apolipoprotein A1 ratio is associated with sex hormone binding globulin and may be an indicator of metabolic syndrome in PCOS women

Objective To identify significant factors related to the apolipoprotein B/apolipoprotein A1 （apoB/A1） ratio and investigate the association between the apoB/A1 ratio and metabolic syndrome （MS） in polycystic ovary syndrome （PCOS） women. Methods Totally 307 subjects with PCOS were collected and recruited fulfilling the revised 2003 Rotterdam diagnostic criteria. MS was diagnosed by the National Cholesterol Education Program-Adult treatment Panel （NCEP-ATP） III criteria. Results The prevalence of MS in PCOS women was 31.6%, whose average age was 26.2 ___＋ 5.2 years. The apoB/A1 ratio was significantly correlated with age, body mass index （BM1）, waist circumference （WC）, hip circumference, waist-to-hip ratio, blood pressure, metabolic abnormalities, sex hormone binding globulin （SHBG）, and free androgen index. In addition, SHBG had a significant association with all five component risk of MS. The increasing apoB/A1 ratio was associated with the prevalence of MS and was one of the risk factors of MS. Conclusion SHBG was considered as an additional potential factor in predicting the metabolic abnormity in PCOS women. The apoB/A1 ratio is associated with SHBG and might be an indicator of MS in PCOS women.

The Study of Apolipoprotein B Gene Polymorphisms by Polymerase Chain Reaction.

Two polymorphic sites of apolipoprotein B（apoB） gene-Xbal and EcoRI were examined in a sample of 103 patients with documented coronary heart disease （CHD） and 100 healthy individuals. It was demonstrated: （1） The frequencies of rare Xallele （presence of Xbal cutting site） and E-allele （absence of cutting site） were significantly higher in CHD patients than those in controls. It was suggested that these genetic variations were associated with CHD. （2） The patients with genotype of XXhad significantly lower

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。

Relation of combined non-high density lipoprotein cholesterol and apolipoprotein B with Gensini Score of coronary atherosclerosis in non-diabetic acute coronary syndrome

Background Non-high-density lipoprotein cholesterol （non-HDL-C） and Apolipoprotein B （apoB） increase car- diovascular disease （CVD） risk, but few studies have explored the correlations of non-HDL-C and apoB with cor- onary atherosclerosis in non-diabetes acute coronary syndrome （ACS）. Methods The study enrolled 443 sub- jects with non-diabetic ACS, and all subject check coronary angiography, and coronary atherosclerosis were eval- uated using Gensini Score （GS） scale including small （GS 1-15）, middle （GS16-43）, and severe （GS≥44）. All sub- jects were classified into 4 groups： High apoB （≥90 mg/dL） and High non-HDL-C （≥130 mg/dL）, High non-HDL -C alone, High apoB alone, and normal apoB and non-HDL-C. Results After adjusted for risk factors, non-HDL -C and apoB were positively correlated with GS （ r = 0.075, P = 0.002 and r = 0.092, P 〈 0.001）. In the GS 0-15, high non-HDL-C ＋ high apoB group 29.3% and high apoB alone group 28.2% were significantly lower than nor- mal non-HDL-C＋ normal apoB group 48% （p = 0.010）. In the GS 16-43, high non-HDL-C alone group 50.4% and high apoB alone group 47.6% were significantly more than high non-HDL-C＋ high apoB group 34.1% （P = 0.036）. In the GS ≥44, high non-HDL-C＋ high apoB group 36.6% was significantly higher than high non-HDL- C alone group 16% and normal non-HDL-C＋ normal apoB 14.2%（P 〈 0.001）. Conclusions The high non-HDL- C and apoB are the risk factors for coronary artery atherosclerosis in non-diabetic ACS.

入院时血清淀粉酶、ApoB/ApoA1水平联合检测对重症急性胰腺炎的预测价值

目的:观察入院时血清淀粉酶、载脂蛋白B(ApoB)/载脂蛋白A1(ApoA1)水平联合检测对重症急性胰腺炎(AP)的预测价值。方法:回顾性分析2020年12月至2023年12月该院收治的86例AP患者的临床资料,按入院后是否发展为重症AP分为重症组(n=40)和非重症组(n=46),检测两组入院时血清淀粉酶、ApoB/ApoA1水平,并采用受试者工作特征(ROC)曲线,分析血清淀粉酶、ApoB/ApoA1水平单项及联合检测对重症AP的预测价值。结果:重症组入院时血清淀粉酶、ApoB/ApoA1水平均高于非重症组,差异有统计学意义(P<0.05);ROC曲线结果显示,入院时血清淀粉酶、ApoB/ApoA1水平联合检测预测重症AP的价值[曲线下面积(AUC)=0.821]高于二者单项预测(AUC=0.795、0.740)。结论:入院时血清淀粉酶、ApoB/ApoA1水平联合检测预测重症AP的价值高于二者单项预测。

Effect of bilobalide B on cholinergic hippocampal neurons exposed to cholesterol and apolipoprotein E4

BACKGROUND： Extracts of ginkgo biloba leaves have been reported to improve nerve function and activity in Alzheimer＇s disease, which is associated with reduced secretion of cholinergic neurotransmitter in hippocampal neurons. OBJECTIVE： To validate the protective effect of bilobalide B against in vitro injury of cholinergic neurons of the hippocampus induced by combined cholesterol and apoE4 DESIGN, TIME AND SETTING： This randomized, controlled animal experiment was performed in the Pathology Laboratory, Tianjin University of Traditional Chinese Medicine from July 2003 to July 2006. MATERIALS： Neonatal Wistar rats, 1-day-old, both male and female, and mean body mass of 5 g were selected for this study. Cholesterol and apolipoprotein E4 （apoE4） were purchased from Sigma Company （USA）, bilobalide B was purchased from Tianjin Zhongyi Pharmaceutical Factory, batch number 20050312. METHODS： Hippocampal neurons were divided into three groups： a normal control group （routinely added media）, a model group （exposed to media containing 40 mg/L cholesterol and 30 mg/L apoE4 for 24 hours） and a bilobalide B group （exposed to media containing 160 mg/L bilobalide B for 16 hours, and then with addition of 40 mg/L cholesterol and 30 mg/L apoE4 for an additional 24 hours）. MAIN OUTCOME MEASURES： Levels of acetylcholine （ACh） and activity of acetylcholinesterase （ACHE） and choline acetyltransferase （CHAT） in hippocampal neurons were determined by microdosage hydroxylamine colorimetry, hydroxylamine colorimetry and radiological chemistry, respectively. RESULTS： The ACh level was significantly lower in the model group than that in the normal control group （P 〈 0.01）, while it was markedly higher in the bilobalide B group than in the model group （P 〈 0.05）. Activity of AChE was significantly decreased in the model group compared with the normal control group （P 〈 0.05）. However, there was no significant difference between the model group and the bilobalide B group （P 〉 0.05）. Activity of ChAT was significantly lower in the model group than in the normal control group （P 〈 0.01）, while the activity was significantly higher in the bilobalide B group than in the model group （P 〈 0.05）. CONCLUSION： Bilobalide B can enhance the ACh level of hippocampal neurons damaged by combined cholesterol and apoE4, by promoting the synthesis, but not the degradation, of ACh.

老年急性脑梗死患者Hcy ApoB/ApoAⅠ及动态动脉硬化指数与颈动脉斑块性质的关系分析

目的:观察老年急性脑梗死(ACI)患者同型半胱氨酸(Hcy)、载脂蛋白B(ApoB)/载脂蛋白AⅠ(ApoAⅠ)及动态动脉硬化指数(AASI)的变化与颈动脉斑块性质的关系。方法:纳入2021年7月至2023年7月本院收治的老年ACI患者103例(稳定性斑块61例,不稳定斑块42例),观察患者Hcy、ApoB/ApoAⅠ及AASI水平,采用单因素分析和多因素Logistic回归分析Hcy、ApoB、ApoAⅠ、AASI与颈动脉斑块性质的关系,并绘制受试者工作特征曲线(ROC)分析三指标对颈动脉斑块性质的评估效能。结果:不稳定斑块组Hcy、ApoB/ApoAⅠ、AASI水平及颈动脉中膜厚度(IMT)明显高于稳定斑块组,差异有统计学意义(P<0.05);Pearson相关性显示:Hcy、ApoB/ApoAⅠ、AASI水平与IMT成正相关,相关性有统计学意义(r=0.354、0.372、0.390,P<0.05);单因素分析显示:合并高血压、糖尿病、高脂血症与颈动脉斑块性质相关,差异有统计学意义(P<0.05);多因素Logistic回归分析显示:合并高血压、糖尿病、高脂血症及Hcy、ApoB/ApoAⅠ、AASI水平是影响颈动脉斑块性质的危险因素,差异有统计学意义(P<0.05);ROC分析显示:Hcy、ApoB/ApoAⅠ、AASI评估颈动脉斑块性质的AUC为0.696、0.711、0.764,三指标联合评估的AUC最高为0.853,最大约登指数下的敏感度和特异度分别为0.952、0.607。结论:老年ACI患者Hcy、ApoB/ApoAⅠ、AASI水平变化与颈动脉斑块性质存在一定的关联,且对不稳定性斑块具有一定的评估价值。

载脂蛋白B联合颈动脉内膜中层厚度对冠心病的预测价值

目的探讨血清载脂蛋白B(apoB)联合颈动脉内膜中层厚度(CIMT)在冠心病中的预测价值。方法回顾性分析2020年1—6月在右江民族医学院附属医院就诊的胸痛疑似冠心病并行冠脉造影的患者210例,根据冠脉造影结果,分为冠心病组和非冠心病组。所有患者检测血清apoB、行颈动脉彩超检查。分析两组患者血清apoB、CIMT、斑块差异,采用受试者工作特征曲线(ROC)分析apoB、CIMT以及二者联合对冠心病的预测价值。结果冠心病组血清apoB、CIMT、颈动脉斑块比例明显高于非冠心病组,差异有统计学意义(P<0.05);冠心病多支病变患者血清apoB、CIMT明显高于单支病变患者,差异有统计学意义(P<0.05);血清apoB和CIMT预测冠心病的价值差异无统计学意义(P>0.05)。两者联合预测冠心病的ROC曲线下面积为0.865,诊断的敏感度和特异度分别为93.20%和63.30%,两者联合预测冠心病的价值优于单独使用血清apoB、CIMT,差异有统计学意义(P<0.05)。结论血清apoB联合CIMT能提高对冠心病的预测价值。

High levels of homocysteine downregulate apolipoprotein E expression via nuclear factor kappa B

AIM: To investigate the effect of high homocysteine(Hcy) levels on apolipoprotein E(apoE) expression and the signaling pathways involved in this gene regulation.METHODS: Reverse transcriptase polymerase chain reaction(RT-PCR) and Western blot were used to assess apo E expression in cells treated with various concentrations(50-500 μmol/L) of Hcy. Calcium phosphatetransient transfections were performed in HEK-293 and RAW 264.7 cells to evaluate the effect of Hcy on apoE regulatory elements [promoter and distal multienhancer 2(ME2)]. To this aim, plasmids containing the proximal apoE promoter [(-500/+73)apoE construct] alone or in the presence of ME2 [ME2/(-500/+73)apoE construct] to drive the expression of the reporter luciferase gene were used. Co-transfection experiments were carried out to investigate the downstream effectors of Hcymediated regulation of apoE promoter by using specific inhibitors or a dominant negative form of IKβ. In other co-transfections, the luciferase reporter was under the control of synthetic promoters containing multiple specific binding sites for nuclear factor kappa B(NF-κB), activator protein-1(AP-1) or nuclear factor of activated T cells(NFAT). Chromatin immunoprecipitation(ChI P)assay was accomplished to detect the binding of NF-κB p65 subunit to the apoE promoter in HEK-293 treated with 500 μmol/L Hcy. As control, cells were incubated with similar concentration of cysteine. NF-κB p65 proteins bound to DNA were immunoprecipitated with anti-p65 antibodies and DNA was identified by PCR using primers amplifying the region-100/+4 of the apoE gene. RESULTS: RT-PCR revealed that high levels of Hcy(250-750 μmol/L) induced a 2-3 fold decrease in apoE m RNA levels in HEK-293 cells, while apo E gene expression was not significantly affected by treatment with lower concentrations of Hcy(100 μmol/L). Immunoblotting data provided additional evidence for the negative role of Hcy in apoE expression. Hcy decreased apoE promoter activity, in the presence or absence of ME2, in a dose dependent manner, in both RAW 264.7 and HEK-293 cells, as revealed by transient transfection experiments. The downstream effectors of the signaling pathways of Hcy were also investigated. The inhibitory effect of Hcy on the apo E promoter activity was counteracted by MAPK/ERK kinase 1/2(MEK1/2) inhibitor U0126, suggesting that MEK1/2 is involved in the downregulation of apoE promoter activity by Hcy. Our data demonstrated that Hcy-induced inhibition of apoE took place through activation of NF-κB. Moreover, we demonstrated that Hcy activated a synthetic promoter containing three NF-κB binding sites, but did not affect promoters containing AP-1 or NFAT binding sites. ChI P experiments revealed that NF-κB p65 subunit is recruited to the apoE promoter following Hcy treatment of cells.CONCLUSION: Hcy-induced stress negatively modulates apoE expression via MEK1/2 and NF-κB activation. The decreased apo E expression in peripheral tissues may aggravate atherosclerosis, neurodegenerative diseases and renal dysfunctions.

载脂蛋白B和绝经后骨质疏松性骨折的相关性分析

目的探究载脂蛋白B(Apo-B)和绝经后骨质疏松性骨折的相关性。方法选取2020年11月至2022年7月于常州市第一人民医院就诊的204例绝经后骨质疏松症患者。依据是否发生过脆性骨折将研究对象分为骨折组(n=91)和非骨折组(n=113),其中椎体骨折66例、髋部骨折6例、肋骨及四肢骨折19例。对比两组一般资料、血脂、骨密度T值、甲状旁腺素(PTH)、维生素D、血钙水平及是否患有高血压或糖尿病等差异。采用二元及多元Logistic回归分析载脂蛋白B与骨折风险的相关性。结果绝经后骨质疏松症患者中,骨折患病率为44.61%。骨折组的年龄和确诊骨质疏松症年龄均高于非骨折组,而总胆固醇、低密度脂蛋白胆固醇、载脂蛋白B、腰椎、股骨颈和全髋T值水平均低于非骨折组,差异有统计学意义(P<0.05)。二元Logistic回归分析发现,当调整了年龄(仅限全年龄段组)、血压、腰椎和全髋T值后,载脂蛋白B在全年龄段组和≤65岁组对骨折具有保护作用(OR=0.239,95%CI:0.079~0.724,P=0.011;OR=0.181,95%CI:0.032~1.020,P=0.048)。多元Logistic回归分析发现,与无骨折组相比,在椎体骨折组中,当调整了年龄、血压、腰椎和全髋T值后,总胆固醇、低密度脂蛋白胆固醇、载脂蛋白B可能是椎体骨折的保护因素(OR=0.609,95%CI:0.418~0.888,P=0.010;OR=0.539,95%CI:0.338~0.860,P=0.010;OR=0.106,95%CI:0.028~0.408,P=0.001),但在髋部、肋骨及四肢骨折病例中,血脂水平与骨折之间未见明显关联(P>0.05);在血脂正常范围内载脂蛋白B对椎体骨折可能具有保护作用(OR=0.048,95%CI:0.008~0.306,P=0.001),当高脂血症时载脂蛋白B的保护作用消失(P>0.05)。结论载脂蛋白B可能是绝经后女性椎体骨质疏松性骨折的保护因素。

ApoB/ApoA1比值、甘油三酯-葡萄糖指数与老年创伤性脑损伤严重程度和预后的关系

目的探讨载脂蛋白B(ApoB)/载脂蛋白A1(ApoA1)比值、甘油三酯-葡萄糖(TyG)指数与创伤性脑损伤(TBI)严重程度和预后的关系。方法选择2018年1月至2023年1月绵阳市中心医院收治的112例TBI病人(TBI组)和79例健康志愿者(对照组)。根据入院时格拉斯哥昏迷评分量表(GCS)评分将TBI病人分为中度组(64例)和重度组(48例),出院6个月后采用格拉斯哥预后量表(GOS)评估神经预后,并据此将TBI病人分为预后不良组(23例)和预后良好组(89例)。收集临床资料,计算ApoB/ApoA1比值和TyG指数,采用Pearson相关系数描述ApoB/ApoA1比值和TyG指数与胰岛素抵抗(HOMA-IR)、GCS评分的相关性,采用多因素Logistic回归分析影响TBI病人预后的因素,采用ROC曲线分析ApoB/ApoA1比值和TyG指数预测TBI病人预后的价值。结果TBI组ApoB/ApoA1比值、TyG指数、HOMA-IR显著高于对照组(P<0.05),且重度组高于中度组(P<0.05)。TBI病人ApoB/ApoA1比值、TyG指数与GCS评分呈负相关(P<0.05),与HOMA-IR呈正相关(P<0.05)。脑室出血、高ApoB/ApoA1比值、高TyG指数、高HOMA-IR是TBI病人预后不良的危险因素(P<0.05)。ApoB/ApoA1比值、TyG指数预测TBI病人预后的AUC分别为0.744、0.755,与HOMA-IR(0.794)接近(P>0.05),联合ApoB/ApoA1比值、TyG指数、HOMA-IR预测TBI病人预后的AUC为0.888,大于各指标单独预测价值(P<0.05)。结论TBI病人ApoB/ApoA1比值、TyG指数增高与神经损伤加重和预后不良有关,检测ApoB/ApoA1比值、TyG指数有助于评估TBI病人预后不良风险。

血清视黄醇结合蛋白、胱抑素C及载脂蛋白B/载脂蛋白A1联合检测对高血压早期肾损伤的诊断价值

目的:探讨视黄醇结合蛋白(RBP)、胱抑素C(Cys-C)及载脂蛋白B/载脂蛋白A1(ApoB/ApoA1)检测对高血压早期肾损伤的诊断价值。方法:选取80例高血压患者为研究对象,根据早期肾损伤诊断标准将其分为单纯高血压组(n=47)及高血压合并早期肾损伤组(n=33)。比较两组患者一般资料、血脂、RBP、Cys-C、ApoB/ApoA1水平,采用Logistic回归分析高血压患者早期肾损伤的危险因素。采用ROC曲线评估RBP、Cys-C、ApoB/ApoA1及其联合对高血压患者早期肾损伤的诊断效能。结果:早期肾损伤组患者RBP、Cys-C、ApoB/ApoA1水平均高于单纯高血压组,ApoA1水平低于单纯高血压组,差异均有统计学意义(P<0.05)。多因素Logistic回归分析显示,RBP、Cys-C、ApoB/ApoA1是原发性高血压患者合并早期肾损伤的危险因素(P<0.05)。ROC分析显示,当RBP≥3.475 mg/L时,诊断原发性高血压患者合并早期肾损伤的曲线下面积(AUC)为0.729,灵敏度为69.7%,特异度为72.3%;当Cys-C≥2.525 mg/L时,AUC为0.768,灵敏度为72.7%,特异度为74.5%;当ApoB/ApoA1≥0.870时,AUC为0.656,灵敏度为63.6%,特异度为68.1%;三者联合诊断的AUC为0.870,灵敏度为81.8%,特异度为80.9%。结论:高血压合并早期肾损伤患者RBP、Cys-C、ApoB/ApoA1水平升高,可将其联合用于高血压合并早期肾损伤的辅助诊断。

载脂蛋白B在心血管疾病风险预测中的应用进展

心血管疾病(CVD)是我国居民非传染性疾病死亡的首要原因,且其患病率逐年升高,已成为人类健康的头号“杀手”。研究表明,载脂蛋白B(ApoB)作为CVD发生风险的危险因素,在评估CVD进展方面具有一定的优势,它能直接测量低密度脂蛋白(LDL)粒子数,且检测不受禁食限制,可作为筛查、诊断和管理CVD的主要测量指标。故该文对ApoB的特点、ApoB评估CVD风险的SWOT分析、降低ApoB水平的方法及其在CVD风险预测中的作用做一综述,以期更好地了解ApoB在CVD风险评估中的临床应用,有助于及早发现、预防和治疗CVD。