Serum cystatin C,monocyte/high-density lipoprotein-C ratio,and uric acid for the diagnosis of coronary heart disease and heart failure

BACKGROUND Coronary heart disease(CHD)and heart failure(HF)are the major causes of morbidity and mortality worldwide.Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis.However,conventional diagnostic methods such as electrocardiography,echocardiography,and cardiac biomarkers have certain limitations,such as low sensitivity,specificity,availability,and cost-effectiveness.Therefore,there is a need for simple,noninvasive,and reliable biomarkers to diagnose CHD and HF.AIM To investigate serum cystatin C(Cys-C),monocyte/high-density lipoprotein cholesterol ratio(MHR),and uric acid(UA)diagnostic values for CHD and HF.METHODS We enrolled 80 patients with suspected CHD or HF who were admitted to our hospital between July 2022 and July 2023.The patients were divided into CHD(n=20),HF(n=20),CHD+HF(n=20),and control groups(n=20).The serum levels of Cys-C,MHR,and UA were measured using immunonephelometry and an enzymatic method,respectively,and the diagnostic values for CHD and HF were evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Serum levels of Cys-C,MHR,and UA were significantly higher in the CHD,HF,and CHD+HF groups than those in the control group.The serum levels of Cys-C,MHR,and UA were significantly higher in the CHD+HF group than those in the CHD or HF group.The ROC curve analysis showed that serum Cys-C,MHR,and UA had good diagnostic performance for CHD and HF,with areas under the curve ranging from 0.78 to 0.93.The optimal cutoff values of serum Cys-C,MHR,and UA for diagnosing CHD,HF,and CHD+HF were 1.2 mg/L,0.9×10^(9),and 389μmol/L;1.4 mg/L,1.0×10^(9),and 449μmol/L;and 1.6 mg/L,1.1×10^(9),and 508μmol/L,respectively.CONCLUSION Serum Cys-C,MHR,and UA are useful biomarkers for diagnosing CHD and HF,and CHD+HF.These can provide information for decision-making and risk stratification in patients with CHD and HF.

Changes and significance of serum inflammatory factors,UA,Hcy and small dense low-density lipoprotein levels in patients with coronary heart disease

Objective: To investigate the changes and significance of serum inflammatory factors, uric acid (UA), homocysteine (Hcy) and small dense low-density lipoprotein (sdLDL-C) levels in patients with coronary heart disease (CHD). Methods: A total of 152 patients with CHD were selected as the CHD group, including stable angina pectoris (SAP group, n=48), unstable angina pectoris (UAP group, n=55), and acute myocardial infarction (AMI group, n=49), according to the Gensinis score, it can be divided into mild group (n=88), moderate group (n=43) and severe group (n=21), at the same time 55 healthy people were selected as control group. The serum inflammatory factors [hypersensitivity C reactive protein (hs-CRP), tumor necrosis factor -α (TNF-α)], UA, Hcy and sdLDL-C levels were compared between patients with different CHD and different degree of coronary artery lesions. Results: The levels of hs-CRP, TNF-α, UA, Hcy and sdLDL-C in the CHD group were significantly higher than those in the control group;In the CHD group, the levels of hs-CRP, TNF-α, UA, Hcy and sdLDL-C in the UAP group and AMI group were significantly higher than those off the SAP group, and the level of AMI group [(7.96±1.49) mg/L, (92.87±14.50) ng/L, (417.75±43.88) mol/L, (23.25±7.33) and mol/L (1.31±0.53) mmol/L] was significantly higher than that of UAP group [(6.15±0.97) mg/L, (73.88±9.27) ng/L, (393.63±68.29) mol/L, (19.67±7.26) mol/L and (1.08±0.44) mmol/L];Compared with mild group hs-CRP, TNF-α, UA, Hcy and sdLDL-C levels, the levels of the moderate group and severe group were significantly increased, and the level of severe group was significantly higher than that of moderate group. Conclusion: The levels of serum inflammatory factors, UA, Hcy and sdLDL-C in patients with coronary heart disease are significantly increased, and the detection of the levels has a great significance for the diagnosis of coronary heart disease and the assessment of the severity of coronary heart disease.

Correlation of serum Hcy and UA contents with coronary plaque property changes in diabetic patients with coronary heart disease

Objective: To study the correlation of serum Hcy and UA contents with coronary plaque property changes in diabetic patients with coronary heart disease. Methods: Patients who were diagnosed with type 2 diabetes mellitus in Dongguan Branch of Yan'an University Affiliated Hospital between May 2013 and June 2017 were selected and divided into the CHD+DM group who were complicated by coronary heart disease and the DM group who were not complicated by coronary heart disease according to the results of coronary CTA, and the healthy subjects who received physical examination in Dongguan Branch of Yan'an University Affiliated Hospital during the same period were selected as control group. The contents of homocysteine (Hcy), uric acid (UA), platelet activation indexes and protease indexes in serum were measured. Results: Serum Hcy, UA, sSema4D, sP-selectin, sE-selectin, MMP1, MMP3, CatK and ADAMTS4 contents of DM group and CHD+DM group were greatly higher than those of control group whereas Klotho and TIMP2 contents were greatly lower than those of control group;serum Hcy, UA, sSema4D, sP-selectin, sE-selectin, MMP1, MMP3, CatK and ADAMTS4 contents of CHD+DM group were greatly higher than those of DM group whereas Klotho and TIMP2 contents were greatly lower than those of DM group;serum sSema4D, sP-selectin, sE-selectin, MMP1, MMP3, CatK and ADAMTS4 contents of CHD+DM group were positively correlated with Hcy and UA contents while Klotho and TIMP2 contents were negatively correlated with Hcy and UA contents. Conclusion: The abnormal increase of serum Hcy and UA contents in diabetic patients with coronary heart disease can promote the activation and aggregation of platelet, the degradation of plaque fibrous cap and the decrease of plaque stability.

Correlation between serum C1q tumor necrosis factor-related protein 4 and high-sensitivity C-reactive protein levels and coronary heart disease

Objective:To investigate the relationship between serum levels of C1q tumor necrosis factorrelated protein 4(CTRP4)and hypersensitive C reactive protein(hs-CRP)and coronary heart disease(CHD)and its clinical value.Methods:128 patients underwent coronary angiography in our hospital,63 males,65 women,Based on blood sugar levels and coronary angiography,Divided into pure coronary heart disease(CHD)group 62 cases,Coronary heart disease with diabetes(DM+CHD)group 66 cases,A total of 126 patients were selected as control group,65 men,61 women,CTRP4 and hs-CRP levels in serum,Using Pearson correlation analysis to assess the correlation between Gennisi score and CTRP4、hs-CRP,Analysis of three groups of biochemical indicators,CTRP4、hs-CRP level changes and clinical significance.Results:The CTRP4、hs-CRP level of DM+CHD group was significantly higher than that of control group and CHD group(P DM+CHD 0.05).The CTRP4、hs-CRP level of the three-vessel coronary artery lesion group in the experimental group was higher than that in the two-vessel lesion group(P﹤0.05),Double branch lesion group was higher than single branch lesion group(P﹤0.05);Correlation analysis shows,There was a significant positive correlation between the CTRP4、hs-CRP level of CHD group and DM+CHD group and the Gennisi score(P DM+CHD 0.05).ROC curves show,CTRP4 and hs-CRP levels had predictive value(CHD group,AUC=0.940,0.934,DM+CHD group,AUC=0.980,0.964),Two associations(CHD:AUC=0.961,P﹤0.001,DM+CHD group:AUCDM+CHD 0.982,P﹤0.001)the predictive value is high.Conclusion:Serum CTRP4 and hs-CRP are positively related to the severity of coronary heart disease,and the sensitivity and specificity of predicting coronary heart disease are high,which is helpful for the identification and early prevention of coronary heart disease,and has certain clinical reference value.

Correlation between serum Hcy content and coronary atherosclerosis severity in patients with H-type hypertension and coronary heart disease

Objective:To analyze the correlation between serum Hcy content and coronary atherosclerosis severity in patients with H-type hypertension and coronary heart disease. Methods: 48 patients with H-type hypertension and coronary heart disease were selected as observation group, and 57 patients with normal hypertension and coronary heart disease were selected as control group. Echocardiography was used to determine coronary lesion parameters, enzyme-linked immunosorbent assay (ELISA) was used to determine serum levels of homocysteine (Hcy) and coronary heart disease-related indexes, and the correlation between Hcy levels and coronary heart disease was further analyzed. Results:Serum Hcy level of observation group was higher than that of control group (P<0.05), absolute GLPSS value and E/A value under echocardiography were less than those of control group while E-DT and E/e value were higher than those of control group (P<0.05);serum adiponectin (APN) level was lower than that of control group while P-selectin, asymmetric dimethylarginine (ADMA), oxidized high-density lipoprotein (OX-HDL), MMP-2, MMP-9, lipoprotein-associated phospholipase A2 (Lp-PLA2) and Resistin levels were higher than those of control group (P<0.05);Hcy was negatively correlated with absolute GLPSS value, E/A value and APN level, and was positively correlated with E-DT value, E/e value as well as P-selectin, ADMA, OX-HDL, MMP-2, MMP-9, Lp-PLA2 and Resistin levels (P<0.05). Conclusions:There is direct correlation between serum Hcy levels and the severity of coronary heart disease in patients with H-type hypertension and coronary heart disease, it can be a reliable way to early screen for coronary heart disease and evaluate the illness, and it is also a new target of coronary heart disease intervention.

Methylenetetrahydrofolate Reductase Gene Polymorphism C677T is Associated with Increased Risk of Coronary Heart Disease in Chinese Type 2 Diabetic Patients

Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus(T2DM).Previous researches report that methylenetetrahydrofolate reductase gene(MTHFR)polymorphisms might influence the occurrence of coronary heart disease(CHD)in T2DM patients.The purpose of this study was to evaluate whether MTHFR C677T and A1298C mutations are associated with the risk of CHD inT2DM patients.Methods A total of 197 subjects with T2DM were studied,of which 95 patients with CHD.The genotypes of MTHFR C677T and A1298C were analyzed by using dideoxy chain-termination method,and compared between patients with CHD and those without CHD.Results We found that the frequency of the 677T allele was significantly higher in T2DM patients with CHD than those without CHD(P=0.011).However,there was no significant difference in any of the examined haplotypes between T2DM patients with and without CHD.Furthermore,the 677T allele was associated with a higher risk of CHD development in diabetic patients with lower homocysteine(Hey)levels(≤15μmol/L)(P=0.006),while no effect of MTHFR gene polymorphism on the incidence of CHD was found in patients with higher Hey levels(>15 μmol/L)(P=0.491).Conclusion The MTHFR C677T gene polymorphism is associated with the risk of CHD of diabetic patients and could be used as an effective marker for CHD in Chinese diabetic populations with normal Hey levels.

Effect of Trimetazidine on Diabetic Patients with Coronary Heart Diseases: A Meta-Analysis of Randomized, Controlled Trials

Objective To explore the therapeutic effects of trimetazidine(TMZ)on diabetic patients with coronary heart diseases.Methods We conducted a comprehensive electronic search of PubMed,EMBASE,and Cochrane databases between the inception dates of databases and May 2019(last search conducted on 30 May 2019)to identify randomized controlled trials.The evaluation method recommended by Cochrane Collaboration for bias risk assessment was employed for quality assessment.Random or fixed models were used to investigate pooled mean differences in left ventricular function,serum glucose metabolism,serum lipid profile,myocardial ischemia episodes and exercise tolerance with effect size indicated by the 95%confidence interval(CI).Results Additional TMZ treatment contributed to considerable improvement of left ventricular ejection fraction(WMD=4.39,95%CI:3.83,4.95,P<0.00001),left ventricular end diastolic diameter(WMD=-3.17,95%CI:-4.90,-1.44,P=0.0003)and left ventricular end systolic diameter(WMD=-4.69,95%CI:-8.66,-0.72,P=0.02).TMZ administration also significantly decreased fasting blood glucose(SMD=-0.43,95%CI:-0.70,-0.17,P=0.001),glycosylated hemoglobin level(WMD=-0.59,95%CI:-0.95,-0.24,P=0.001),serum level of total cholesterol(WMD=-20.36,95%CI:-39.80,-0.92,P=0.04),low-density lipoprotein cholesterol(WMD=-20.12,95%CI:-32.95,-7.30,P=0.002)and incidence of myocardial ischemia episodes(SMD=-0.84,95%CI:-1.50,-0.18,P=0.01).However,there were no significant differences in serum triglyceride level,high-density lipoprotein cholesterol,exercise tolerance between the TMZ group and the control group.Conclusion TMZ treatment in diabetic patients with coronary heart disease is effective to improve cardiac function,serum glucose and lipid metabolism and clinical symptoms.

High Density Lipoprotein Phospholipids as a Marker of Coronary Heart Disease of Shen-Yang Deficiency Syndrome

Objective: To seek a new biochemical index for diagnosis of coronary heart disease (CHD) of shen-Yang deficiency syndrom (CHD-SYD). Methods: Sixty-one patients with CHD were divided into 3 groups according to their TCM Syndrome type, 10 patients in the group without Xin-Qi deficiency (Group A), 25 in the group with Xin-Qi deficiency but without Shen-Yang deficiency (Group B) and 26 in the group both with Xin-Qi deficiency and Shen-Yang deficiency (Group C). Levels of 17-hydroxy-corticoste-roid in urine (urinary 17-OHCS) per 24 hrs, and serum level of high density lipoprotein cholesterol (HDL-C) and high density lipoprotein phospholipid (HDL-PL) in them were determined in synchrostep and compared with those in the control group of 23 healthy aged persons, urinary 17-OHCS per 24 hrs was taken as the diagnostic standard to screen a new index for diagnosis of Shen-Yang deficiency Syndrome, and preliminary appraisal to the index was made. Results: Serum HDL-PL in the CHD-SYD patients( Group C) was 616+157 mg/L, which was obviously lower than that in the patients of Group A and B. With low HDL-PL(<650 mg/L) used as the index to diagnose CHD-SYD, the sensitivity was 73%, the specificity 86% and the accuracy 80%. Conclusion: HDL-PL <650 mg/L could be adopted as an index for CHD-SYD diagnosis, which is simple and practical.

Study on the relationship between Lp-PLA2, D- dimer and Galectin-3 and atherosclerotic vulnerable plaque in patients with coronary heart disease

Objective: To explore the relationship and clinical value of serum phospholipase A2 (Lp-PLA2), d-dimers, and serum galectin-3 (galectin-3) with atherosclerotic vulnerable plaques in coronary artery patients with coronary heart disease. Methods: A total of 248 patients who underwent coronary angiography (CAG) and intravascular ultrasound (IVUS) in our hospital from June 2017 to September 2018 were selected and divided into vulnerable plaque group (89), stable plaque group (89) and control group (70) according to the examination results. The serum levels of Lp-PLA2, d-dimer and galectin-3 in three groups were compared, as well as their correlation with the detection parameters. To evaluate the clinical value of Lp-PLA2, d-dimer and galectin-3 in patients with coronary heart disease (CHD) with atherosclerotic vulnerable plaque. Results: Serum Lp-PLA2, d-dimer and galectin-3 levels were significantly different from the three groups (P<0.05), and the control group < stable plaque group <vulnerable plaque group (P<0.05). Correlation analysis showed that Lp-PLA2, d-dimer and galectin-3 were significantly positively correlated with plaque area, plaque load, necrotic core and calcified tissue (P<0.01), and negatively correlated with fibrous lipid and fibrous tissue (P<0.01). ROC curve showed that Lp-PLA2, d-dimer and galectin-3 had certain predictive value for vulnerable coronary atherosclerotic plaques (AUC=0.939, 0.977, 0.920, P<0.01), and the three combinations (AUC=0.986, P<0.01) had higher predictive value. Conclusion: Serum Lp-PLA2, d-dimer and galectin-3 are significantly correlated with coronary atherosclerotic vulnerable plaques in patients with coronary heart disease, with high sensitivity and specificity, which can be used for the diagnosis and treatment of early atherosclerotic vulnerable plaques.

Effect of fluvastatin combined with β-receptor-blockers on cardiac function and peripheral blood NF-κB and sST2 in patients with coronary heart disease complicated with heart failure

Objective: To investigate the effects of fluvastatin combined with β-receptor-blockers on cardiac function and peripheral blood NF-κB and sST2 in patients with coronary heart disease (CHD) complicated with heart failure. Methods: A total of 90 CHD patients complicated with heart failure from September 2016 to September 2017 were selected and randomly divided into the control group and the observation group, with 45 cases in each group. The control group was treated with arotinolol and the observation group was treated with arotinolol combined with fluvastatin. The clinical efficacy of the two groups after treatment was compared. The cardiac function index, blood lipid index, inflammatory factor and serum NF-κB and sST2 levels were detected and compared between the two groups. Results: The effective rate of the observation group was significantly higher than that of the control group (P<0.05). After treatment, the cardiac function indexes of the two groups were significantly improved (P<0.05). The LVEF and LVFS of the observation group were significantly higher than those of the control group, and LVEDD and LVESD of the observation group were significantly lower those of the control group (P<0.05). The serum lipid index and inflammatory factors of the two groups were significantly decreased after treatment. The hs-CRP, TNF-α, TC and LDL-C of the observation group were significantly lower than those of the control group after treatment (P<0.05). After treatment, the serum NF-κB and sST2 were significantly decreased in both groups, and the serum NF-κB and sST2 in the observation group were significantly lower than those in the control group. There was no significant difference in the incidence of adverse reactions between the two groups (P<0.05). Conclusions: Fluvastatin combined with β-receptor-blockers can reduce the level of blood lipid and inflammatory factors more effectively and improve the clinical efficacy of the CHD patients complicated with heart failure. It can effectively reduce serum NF-κB and sST2 more effectively and improve prognosis.

Research survey and review of the effect of Compound Danshen Dripping Pills on the uric acid metabolism of patients with coronary heart disease

A growing number of studies have reported that serum uric acid（SUA） is associated with coronary heart disease（CHD）, which has been increasingly recognized and valued by the medical community. This paper surveys the epidemiological studies of hyperuricemia and CHD and summarizes the clinical study discussing the association between hyperuricemia and coronary heart disease with a prospect of exploring the possible mechanisms of compound Danshen dripping pills in reducing SUA in patients with coronary heart disease.

Hyperhomocysteinemia and hyperlipidemia in coronary heart disease

bjective To examine the relationship between coronary heart disease (C HD) and serum lipid, plasma homocysteine (HCY) as well as the factors related to HCY metabolisms Methods The mutation of the 677CT transition of 5,10methylenetetrah ydrofolate reductase(MTHFR) was determined by PCRbased assay Wholeblood an d plasma folate and plasma vitamin B12, as cofactors of MTHFR, were determi ned by radioimmunologic assay Plasma HCY was determined by HPLC Results Patients with CHD had elevated plasma HCY concentrations (173 8 194?mol/L vs 1025157?mol/L, P <001) In patients w ith my ocardial infarction (MI) and family history (FH) of CHD, plasma HCY were elevate d even higher ( P <005) Plasma HCY concentrations had significant no nlinear inverse correlation with plasma folate and B12 concentrations, i e the lower the serum folate or B12 concentrations, the higher the plasma HC Y co ncentrations ( P <001) Patients with homozygous mutants had higher p lasma HCY concentrations Patients with CHD had increased serum Chol and LDLC and ApoB levels ( P <001, P <005 and P <0 05 respectively) But plasma HCY concentrations had no correlation with serum lip i d levels 241% of the patients had high lipid and high HCY level, 259% had hig h lipid level and normal HCY level, 204% had normal lipid and high HCY level, and 296% had normal lipid and HCY level Conclusions HCY may have strong association with the genesis of CHD L o w plasma folate and B12 concentrations may induce Hyperhomocysteinemia Plasma HCY concentrations have no correlation with serum lipid lev els, so H C Y may be an independent risk factor CHD may be induced by different mechanisms and can be classified into hyperlipidemia, HH(e) and normolipidemia, and normoho mocysteinemia

2型糖尿病合并冠心病患者血清Hcy、HbAlc和血尿酸水平变化的临床意义

目的探讨2型糖尿病合并冠心病患者血清同型半胱氨酸(Hcy)、糖化血红蛋白(HbAlc)和血尿酸水平变化的临床意义。方法选取2型糖尿病合并冠心病患者60例为合并冠心病组,单纯2型糖尿病患者45例为单纯糖尿病组,健康志愿者30名为健康对照组。采集空腹外周静脉血,检测血清Hcy、HbAlc及血尿酸水平;行冠状动脉造影检查,记录冠脉狭窄程度50%及以上的病变累及左前降支、回旋支或右冠脉的支数(单支病变、双支病变、多支病变)。收集2型糖尿病合并冠心病患者的年龄、性别、身高、体质量、吸烟情况及低密度脂蛋白、总胆固醇、甘油三酯、空腹血糖、维生素B12、叶酸水平。进行3 a随访,记录患者病情加重再入院、死亡情况。结果合并冠心病组血清Hcy、HbAlc及血尿酸水平明显高于单纯糖尿病组和健康对照组(P<0.05);多支病变患者血清Hcy、HbAlc及血尿酸水平明显高于双支病变和单支病变患者(P<0.05);预后不良组患者血清Hcy、HbAlc及血尿酸水平明显高于预后良好组患者(P<0.05);预后不良组患者中吸烟比例、空腹血糖水平明显高于预后良好组(P<0.05)。Hcy、HbAlc、血尿酸是2型糖尿病合并冠心病患者预后的独立影响因素。ROC曲线分析显示,血清Hcy、HbAlc及血尿酸水平对2型糖尿病合并冠心病患者预后具有较高的预测价值(P<0.05),联合检测的预测价值最高(AUC=0.947)。结论2型糖尿病合并冠心病患者血清Hcy、HbAlc及血尿酸水平升高,且与冠脉病变程度密切相关,联合检测可用于患者预后评估。

High-density lipoprotein associated factors apoA-I and serum amyloid A in Chinese non-diabetic patients with coronary heart disease

Background High-density lipoprotein cholesterol（HDL-C）levels are a strong,independent inverse predictor of coronary heart disease （CHD）.In this cross-sectional study we investigated the interrelationships between HDL-C and HDL relaled factors apolipoprotein A-I（apoA-I）and serum amyloid A（SAA）and the presence and extent of CHD in a population of Chinese patients with CHD. Methods Two hundred and twenty-four consecutive patients took part in this study.Demographic data were obtained from hospital records.Serum chemical concentrations were measured by standard laboratory methods.Reaults The concentrations of high-sensitive C-reactive protein（hsCRP）（median：1.85 mg/L）and SAP,（median：9.40 mg/L）were significantly higher in the CHD group（P〈0.05）,while concentrations of HDL-C（0.03±0.25）mmol/L）and apoA-I（（604.59±1 05.79）mmol/L）were significantly lower than those in the non-CHD group（P〈0.05）.The concentrations of apoA-l decreased with the increase in vascular damage.but the difference did not reach statistical significance.However, the concentrations of hsCRP and SAA increased with the increase in vascular damage.The unadjusted odd ratios（ORs）（CI） for apoA-I and SAA of the presence of CHD were 0.093（0.990-0.997）（P=0.00）and 2.571（1.029-6.424）（P〈0.05）,respectively.The association between elevated SAA and the presence of CHD was lost after adjusting for lipid status parameter concentrations.The associations between apoA-I.SAA and the extent of CHD remained strong,regardless of confounding variables.Conclusions Increased concentrations of SAA represent the inflammatory marker of the extent of coronary stenosis in patients with CHD.In contrast to SAA, the level of apoA-I was also associated with the presence of CHD, indicating that apoA-I was not only a marker of CHD presence but also a quantitative indicator of CHD extent.In short.determining the change apolipoprotein content within HDL particle is a more accurate and effective method to evaluate the impact of HDL on CHD.

The relationship between serum amyloid A and apolipoprotein A-I in high-density lipoprotein isolated from patients with coronary heart disease

Background Alteration in the protein composition of high-density lipoprotein （HDL） has been proposed as a mechanism for the development of coronary heart disease （CHD）.In HDL,an increase in serum amyloid A protein （SAA） accompanying the decrease in apolipoprotein A-I （apoA-I） has been found during the acute inflammation period.However,whether this phenomenon persists in CHD patients,a disease related to inflammation,is unknown.The purpose of the present study was to explore the relationship between SAA and apoA-I in HDL isolated from CHD patients.Methods Overall,98 patients with confirmed stable CHD and 90 control subjects matched for age and gender were enrolled in this case-control study.Potassium bromide （KBr） density gradient ultracentrifugation was used to isolate HDL from plasma.The levels of SAA and apoA-I in the HDL samples were detected by enzyme-linked immunosorbent assay kits.Pearson＇s correlation and general linear models were used in the analysis.Results Compared with controls,patients with CHD had a significant decrease in the amount of apoA-I （（14.21±8.44） μg/ml vs.（10.95±5.95） μg/ml,P =0.003） in HDL and a significant increase in the amount of log SAA （1.21±0.46 vs.1.51±0.55,P 〈0.00001）.Differences were independent of age,body mass index （BMI）,HDL cholesterol （HDL-C）,and other factors.An independently and statistically significant positive correlation between log SAA and apoA-I in HDL was observed only in the CHD group （β =2.0,P =0.026）.In the general linear model,changes in Iog（SAA）,age,age2,gender,BMI and HDL-C could explain a statistically significant 43% of the variance in apoA-I.Conclusions This study provides direct evidence for the first time that there was an independent positive correlation between log SAA and apoA-I in the HDL of CHD patients,indicating the alteration of protein composition in HDL.However,the question of whether this alteration in HDL is associated with impairment of HDL functions requires further research.

冠心病血清外泌体介导的lncRNA-miRNA-mRNA ceRNA调控网络研究及潜在靶向中药预测及实验验证

目的本研究采用生物信息学相关方法对冠心病(coronary heart disease,CHD)患者和正常人的血清外泌体测序数据分析,构建出竞争性内源性lncRNA-miRNA-mRNA(ceRNA)调控网络,并挖掘预测潜在的中药,并对ceRNA网络涉及的生物学过程和核心中药进行初步验证。方法利用exoRbase数据库获得差异基因的表达矩阵,结合生信方法构建ceRNA网络,并对网络中的差异的mRNA进行GO分析和KEGG分析,利用COREMINE数据库对ceRNA网络涉及的生物学过程及核心靶基因进行预测,筛选具有潜在治疗作用的中药;体外构建AVECs氧化损伤细胞模型,检测细胞骨架、成管功能、细胞增殖、LDH漏出率、ROS水平以及p-AKT、AKT、p-PI3K、PI3K蛋白表达情况,验证核心中药丹参治疗CHD的作用通路及靶点。结果与正常人比,CHD血清外泌体存在395个mRNA,80个miRNA,60个lncRNA差异基因,预测出80个miRNA,所构建ceRNA子网络,主要由21个lncRNA、80个miRNA、82个mRNA组成;AKT1、VEGFA、IL-1β等基因在网络中处于核心地位,异常表达的mRNA涉及细胞的氧化应激反应等生物学过程和PI3K/Akt等信号通路,丹参、川芎、三七等与CHD外泌体介导的生物学过程和核心基因最为密切;药物主要归属于补虚类、清热类和活血化瘀类,五味大多数归属于苦、甘和辛类,归经多集聚于心、肝、肾经;核心中药丹参的有效成分丹参酮IIA可以促进血管内皮细胞增殖、成管、骨架形成及修复,降低细胞LDH漏出率及ROS水平,促进p-AKT、p-PI3K蛋白的表达。结论CHD血清外泌体存在复杂的ceRNA调控网络转导,中药可通过多靶点干预治疗,丹参、川芎、三七等有望成为候选中药来源,其中丹参有效成分丹参酮IIA激活PI3K/Akt信号通路发挥对氧化应激损伤细胞的保护作用,治疗CHD。

Association between SNP rs1800875,serum chymase and immunoglobulin E levels in patients with coronary heart disease

Objective:The gene for mast cell chymase (CMA1) is an ideal candidate for investigating the genetic predisposition to coronary heart disease (CHD),as activated mast cells have been found to be present in a greater proportion in the shoulder region of atheroma than in normal coronary intimae.Previous studies have indicated that CMA1 promoter polymorphism rs1800875 may be involved in regulating immunoglobulin E (IgE) levels in patients with eczema,and it is associated with the progression of immunoglobulin A nephropathy.Methods:The association between single nucleotide polymorphism (SNP) rs1800875,serum chymase,and serum IgE levels was examined in 175 CHD subjects and 95 non-CHD subjects.Results:Statistical analysis indicated no significant difference in allele frequency between CHD and non-CHD.However,a significant association was found between CMA1 genotypes and total IgE levels in CHD subjects.Meanwhile,crossover analysis revealed that,in GG homozygotes,CHD risk was nearly six times higher in those with IgE (U/ml) level <2.58 (natural logarithm conversion),while no association was found with chymase level.Conclusions:Polymorphism rs1800875 of CMA1 may be associated with serum IgE level in CHD subjects,but not with chymase level in both groups.In GG homozygotes,high IgE level is a protective factor against coronary disease.

高效液相色谱联合2,2′-二硫二吡啶衍生反应测定人血清不同类型游离巯基及其与冠心病的关系分析

游离巯基对于心血管疾病的诊断和治疗具有潜在的临床预示价值,本研究建立了一种基于2,2′-二硫二吡啶衍生反应的高效液相色谱测定人血清游离巯基的分析方法,能够同时获得人血清中总游离巯基(Total-SH)、小分子化合物形态游离巯基(LMM-SH)、蛋白质形态游离巯基(P-SH)三者的含量。选用Agilent Eclipse XDB-C18色谱柱(150 mm×4.6 mm,5μm),以0.1%甲酸水溶液-0.1%甲酸乙腈溶液为流动相,在1 mL/min的流速下进行梯度洗脱,5 min内可实现良好的色谱峰基线分离,其中2-硫代吡啶酮色谱峰代表血清样本中总游离巯基含量,吡啶二硫衍生物色谱峰代表小分子化合物形态游离巯基含量,二者差值为蛋白质形态游离巯基含量。本研究对衍生反应条件进行了优化,并进行了方法学验证,结果表明,该方法线性关系良好,相关系数≥0.9994,线性范围为31.25~1000μmol/L,Total-SH和LMM-SH的检出限分别为2.61μmol/L和0.50μmol/L,定量限分别为8.71μmol/L和1.67μmol/L;加标回收率为91.1%~106.0%,日内精密度和日间精密度为0.4%~9.1%。使用本方法测定了714名志愿者的血清样本,总游离巯基浓度为376.60~781.12μmol/L,平均浓度为555.62μmol/L;小分子化合物形态游离巯基的浓度为36.37~231.65μmol/L,平均浓度为82.34μmol/L;蛋白质游离巯基浓度为288.36~687.74μmol/L,平均浓度为473.27μmol/L。Spearman相关性检验分析发现,血清游离巯基浓度与冠心病严重程度及常见临床生化指标存在密切关联。本研究提供了一种简便可靠的血清游离巯基分析方法,探索了其与冠心病的关系,为冠心病风险相关标志物的研究提供了新的参考指标。

CTA参数及Hcy与冠状动脉病变程度的相关性及其对预后的预测价值

目的探讨CT血管造影(CTA)参数及同型半胱氨酸(Hcy)与冠状动脉(简称冠脉)病变程度的相关性及其对预后的预测价值。方法回顾性选取2019年6月至2020年9月新乡医学院第一附属医院收治的98例冠心病(CHD)患者,纳入研究组,根据1∶1选例原则,另选取同期、同年龄段健康体检者98例,纳入对照组。比较两组、不同冠脉病变程度及不同预后患者CTA参数[最小管腔直径(MLD)、最小管腔面积(MLA)、斑块总体积(TPV)]及血清Hcy水平,分析CTA参数及血清Hcy水平与冠脉病变程度之间的相关性,并分析联合应用对预后情况的预测价值。结果观察组CTA参数MLD、MLA值小于对照组,TPV值及血清Hcy水平高于对照组(P<0.05)。不同冠脉病变程度患者MLD、MLA值比较:重度病变<中度病变<轻度病变。TPV值及血清Hcy水平比较:重度病变>中度病变>轻度病变(P<0.05)。MLD、MLA值与冠脉病变程度呈负相关,TPV值及血清Hcy水平与之呈正相关(P<0.05)。预后不良患者MLD、MLA值小于预后良好患者,TPV值及血清Hcy水平高于预后良好患者,且联合预测CHD患者预后不良的曲线下面积为0.899,最佳诊断敏感度为90.16%,最佳诊断特异度为89.19%,约登指数0.794。结论CTA参数MLD、MLA、TPV值及血清Hcy水平与CHD患者冠脉病变程度具有一定相关性,联合应用对预后不良具有一定预测价值,可作为临床评估病变程度及预后的有效方案之一。