Reduced serum high-density lipoprotein cholesterol levels and aberrantly expressed cholesterol metabolism genes in colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a common malignant tumor of the gastrointestinal tract.Lipid metabolism,as an important part of material and energy circulation,is well known to play a crucial role in CRC.AIM To explore the relationship between serum lipids and CRC development and identify aberrantly expressed cholesterol metabolism genes in CRC.METHODS We retrospectively collected 843 patients who had confirmed CRC and received surgical resection from 2013 to 2015 at the Cancer Hospital of the Chinese Academy of Medical Sciences as our research subjects.The levels of serum total cholesterol(TC),triglycerides,low-density lipoprotein cholesterol(LDL-C),highdensity lipoprotein cholesterol(HDL-C),LDL-C/HDL-C and clinical features were collected and statistically analyzed by SPSS.Then,we used the data from Oncomine to screen the differentially expressed genes(DEGs)of the cholesterol metabolism pathway in CRC and used Gene Expression Profiling Interactive Analysis to confirm the candidate DEGs.PrognoScan was used to analyze the prognostic value of the DEGs,and Search Tool for the Retrieval of Interacting Genes was used to construct the protein-protein interaction network of DEGs.RESULTS The serum HDL-C level in CRC patients was significantly correlated with tumor size,and patients whose tumor size was more than 5 cm had a lower serum HDL-C level(1.18±0.41 mmol/L vs 1.25±0.35 mmol/L,P<0.01)than their counterparts.In addition,TC/HDL(4.19±1.33 vs 3.93±1.26,P<0.01)and LDL-C/HDL-C(2.83±1.10 vs 2.61±0.96,P<0.01)were higher in patients with larger tumors.The levels of HDL-C(P<0.05),TC/HDL-C(P<0.01)and LDL-C/HDL-C(P<0.05)varied in different stages of CRC patients,and the differences were significant.We screened 14 differentially expressed genes(DEGs)of the cholesterol metabolism pathway in CRC and confirmed that lipoprotein receptor-related protein 8(LRP8),PCSK9,low-density lipoprotein receptor(LDLR),MBTPS2 and FDXR are upregulated,while ABCA1 and OSBPL1A are downregulated in cancer tissue.Higher expression of LDLR(HR=3.12,95%CI:1.77-5.49,P<0.001),ABCA1(HR=1.66,95%CI:1.11-2.48,P=0.012)and OSBPL1A(HR=1.38,95%CI:1.01-1.89,P=0.041)all yielded significantly poorer DFS outcomes.Higher expression of FDXR(HR=0.7,95%CI:0.47-1.05,P=0.002)was correlated with longer DFS.LDLR,ABCA1,OSBPL1A and FDXR were involved in many important cellular function pathways.CONCLUSION Serum HDL-C levels are associated with tumor size and stage in CRC patients.LRP8,PCSK9,LDLR,MBTPS2 and FDXR are upregulated,while ABCA1 and OSBPL1A are downregulated in CRC.Among them,LDLR,ABCA1,OSBPL1A and FDXR were valuable prognostic factors of DFS and were involved in important cellular function pathways.

High-density Lipoprotein Cholesterol and In-hospital Mortality in Patients with Acute Aortic Dissection

The association between high-density lipoprotein cholesterol（HDL-C） and mortality in patients with acute aortic dissection（AAD） is unclear. From January 2007 to January 2014, a total of 928 consecutive AAD patients who were admitted within 48 h after the onset of symptoms were enrolled in the study. Patients were divided into two groups according to whether serum HDL-C level was below the normal lower limit or not. The Cox proportional hazard regression model was used to identify the predictive value of HDL-C for in-hospital mortality in patients with AAD. As compared with normal HDL-C group（n=585）, low HDL-C group（n=343） had lower levels of systolic blood pressure and hemoglobin and higher levels of leukocyte, alanine aminotransferase, blood glucose, blood urea nitrogen, creatinine and urea acid. Low HDL-C group had significantly higher in-hospital mortality than normal HDL-C group（21.6% vs. 12.6%, log-rank=10.869, P=0.001）. After adjustment for baseline variables including demographics and biologic data, the increased risk of in-hospital mortality in low HDL-C group was substantially attenuated and showed no significant difference（adjusted hazard ratio, 1.23; 95% confidence interval, 0.86–1.77; P=0.259）. Low HDL-C is strongly but not independently associated with in-hospital mortality in patients with AAD.

A Possible Mechanism Linking Hyperglycemia and Reduced High-density Lipoprotein Cholesterol Levels in Diabetes

This study investigated the role of glucose in the biogenesis of high-density lipoprotein cholesterol(HDL-C).Mouse primary peritoneal macrophages were harvested and maintained in Dulbecco’s modified Eagle’s medium(DMEM) containing glucose of various concentrations.The cells were divided into 3 groups in terms of different glucose concentrations in the cultures:Control group(5.6 mmol/L glucose),high glucose concentration groups(16.7 mmol/L and 30 mmol/L glucose).ATP-binding cassette transporter A1(ABCA1) mRNA expression in the macrophages was detected by semi-quantitative RT-PCR 24,48 and 72 h after glucose treatment.The results showed that ABCA1 mRNA expression in the 16.7 mmol/L glucose group was not significantly different from that in the control group at all testing time points(P>0.05 for each).In the 30 mmol/L glucose group,macrophage ABCA1 mRNA expression was not changed significantly at 24 h(P=0.14),but was substantially decreased by 40.4% at 48 h(P=0.009) and by 48.1% at 72 h(P=0.015) as compared with that in the control group.It was concluded that ABCA1 is of vital importance for HDL-C biogenesis.High glucose may hamper HDL-C biogenesis by decreasing ABCA1 expression,which contributes to low HDL-C level in diabetes.

High-density lipoprotein endocytosis in endothelial cells

AIM: To describe the way stations of high-density lipoprotein(HDL) uptake and its lipid exchange in endothelial cells in vitro and in vivo. METHODS: A combination of fluorescence microscopy using novel fluorescent cholesterol surrogates and electron microscopy was used to analyze HDL endocytosis in great detail in primary human endothelial cells. Further, HDL uptake was quantified using radio-labeled HDL particles. To validate the in vitro findings mice were injected with fluorescently labeled HDL and particle uptake in the liver was analyzed using fluorescencemicroscopy. RESULTS: HDL uptake occurred via clathrin-coated pits, tubular endosomes and multivesicular bodies in human umbilical vein endothelial cells. During uptake and resecretion, HDL-derived cholesterol was exchanged at a faster rate than cholesteryl oleate, resembling the HDL particle pathway seen in hepatic cells. In addition, lysosomes were not involved in this process and thus HDL degradation was not detectable. In vivo, we found HDL mainly localized in mouse hepatic endothelial cells. HDL was not detected in parenchymal liver cells, indicating that lipid transfer from HDL to hepatocytes occurs primarily via scavenger receptor, class B, type Ⅰ mediated selective uptake without concomitant HDL endocytosis. CONCLUSION: HDL endocytosis occurs via clathrincoated pits, tubular endosomes and multivesicular bodies in human endothelial cells. Mouse endothelial cells showed a similar HDL uptake pattern in vivo indicating that the endothelium is one major site of HDL endocytosis and transcytosis.

Higher testosterone levels are associated with increased highdensity lipoprotein cholesterol in men with cardiovascular disease： results from the Massachusetts Male Aging Study

Aim： To study the relationship between circulating androgens （total testosterone [TT], free testosterone [IT] and dihydrotestosterone [DHT]） and high-density lipoprotein cholesterol （HDL-C） in men with and without cardiovascular disease （CVD）. Methods： Cross-sectional analyses included 1 661 baseline samples from the Massachusetts Male Aging Study （MMAS）, a population-based cohort of men ages 40-70 years. Serum hormones were measured by radioimmunoassay and HDL-C was determined following precipitation of the lower density lipoproteins. CVD was determined by self-report. Analyses were performed using multiple linear regression. Results： TT and HDL-C were positively correlated in the entire sample （r = 0.11, P = 0.0001）. After adjusting for confounders, we found this relationship was mostly limited to the 209 men with CVD. Among men with CVD, TT （P = 0.0004）, iT （P = 0.0172） and DHT （P = 0.0128） were all positively correlated with HDL-C, whereas in men without CVD only TT correlated with HDL-C （P = 0.0099）. Conclusion： Our results suggest that if androgens contribute to CVD in middle-aged men, the effect is not related to a suppressive effect of endogenous T on HDL-C. （Asian JAndrol 2008 Mar; 10： 193-200）

Lipoprotein in cholesterol transport: Highlights and recent insights into its structural basis and functional mechanism

Lipoproteins are protein-lipid macromolecular assemblies which are used to transport lipids in circulation and are key targets in cardiovascular disease （CVD）. The highly dynamic lipoprotein molecules are capable of adopting an array of conformations that is crucial to lipid transport along the cholesterol transport pathway, among which high-density lipopro- tein （HDL） and low-density lipoprotein （LDL） are major players in plasma cholesterol metabolism. For a more detailed illustration of cholesterol transport process, as well as the development of therapies to prevent CVD, here we review the functional mechanism and structural basis of lipoproteins in cholesterol transport, as well as their structural dynamics in the plasma lipoprotein （HDL and LDL） elevations, in order to obtain better quantitative understandings on structure-function relationship of lipoproteins. Finally, we also provide an approach for further research on the lipoprotein in cholesterol transport.

Could Low Hdl-Cholesterol Levels Be an Unvalued Predictor of Cancer Risk?: A Retrospective Case Study

Background: The relationship between serum lipid profile levels and cancer risk remained uncertain. Recently, it had been reported a significant inverse association between high-density lipoprotein cholesterol (HDL) and the risk of incident cancer that was independent of low-density lipoprotein cholesterol (LDL), age or sex. Objective: The aim of our study was to evaluate the behavior of HDL in cancer patients and in healthy population. Methods: We created a retrospectively search strategy in the laboratory information system (LIS). We filtered and searched those patients with CEA within 5 - 20 ng/ml and any value of HDL and corroborated the presence of cancer (Group 1 (G1)) or not (Group 2 (G2)). Moreover, we searched a control group (patients in outpatient oncology clinic) to observe the values of HDL. Comparisons and statistical logistic regression models were applied to link the levels of this biomarkers and cancer risk. Results: We examined 852 valid patients, median age 62 (50 - 73) years. Within the search strategy group, G2 showed highest levels of HDL (54 (43 - 67) mg/dl) and lowest CEA levels (6.7 (5.7 - 8.4) ng/ml) comparing with G1: HDL (47 (37 - 60) mg/dl) and the CEA (7.9 (6.2 - 10.9) ng/ml);p p r2: 0.092;p p = 0.001)] and CEA [OR: 1.115 (1.060 - 1.174), (p < 0.001)] and they were confirmed as independent predictors of cancer. Conclusion: Our findings confirmed the inverse association of HDL levels between healthy populations and were diagnosed with cancer. Moreover, in a random population, patients with cancer presented lower HDL values compared to those without cancer. Therefore, it could demonstrate the possible positive predictive value of low HDL related to cancer risk.

An Analysis of Health Factors Affecting Employees’ Absenteeism: Influences of HDL Cholesterol and Blood Sugar Levels

Background: Workers’ health condition is an important issue. It affects not only the well-being of workers but also the firms and society as a whole through medical costs and productivity losses due to absenteeism and presenteeism. Data and Methods: Data were obtained from 1136 employees at an operational site of a large corporation. The dataset contained both medical checkups and working record information. Health factors affecting long-term absence (over three days in three months) were analyzed. Logistic regression models and the procedure for selecting proper covariates based on likelihood test statistics and the Akaike information criterion were used. Results: Among health factors, high-density lipoprotein cholesterol (HDL-C) and blood sugar levels were important in the selected model. For HDL-C, the odds ratio (OR) based on one standard deviation difference was 0.75 with a 95% confidence interval (CI) of 0.59 - 0.95. For blood sugar, the OR was 1.20 with a 95% CI of 1.01 - 1.42. Improving HDL-C and blood sugar levels would reduce long-term absence by 25% and 20%, respectively. Conclusion: Controlling HDL-C and blood sugar levels is important to reduce long-term absenteeism. These factors can be improved by modifying eating habits. Since the operational site has its own company cafeterias, which most employees use, nutritional intervention is relatively easy with little or no cost. It may be worthwhile to implement nutritional intervention, especially for patients with low HDL-C or high blood sugar levels. Limitations: The results of this study were based on one operational site of a corporation. The employees were mainly operators working inside the building. The results may be different from other types of jobs and working conditions, such as fieldwork. Analyses of different types of jobs and working conditions are necessary.

Triglycerides and ratio of triglycerides to high-density lipoprotein cholesterol are better than liver enzymes to identify insulin resistance in urban middle-aged and older non-obese Chinese without diabetes

Background Insulin resistance （IR） plays an important pathophysiological role in the development of diabetes,dyslipidemia,hypertension,and cardiovascular disease.Moreover,IR can occur even in non-obese people without diabetes.However,direct detection of IR is complicated.In order to find a simple surrogate marker of IR early in nonobese people,we investigate the association of commonly-used biochemical markers （liver enzymes and lipid profiles） with IR in urban middle-aged and older non-obese Chinese without diabetes.Methods This cross-sectional study included 1 987 subjects （1 473 women）.Fasting blood samples were collected for measurement of glucose,insulin,liver enzymes,lipid profiles and creatinine.Subjects whose homeostasis model of assessment-IR （HOMA-IR） index values exceeded the 75th percentile （2.67 for women and 2.48 for men） of the population were considered to have IR.The area under the receiver operating characteristic curve （ROC） was used to compare the power of potential markers in identifying IR.Results Triglycerides （TG） and ratio of TG to high-density lipoprotein cholesterol （TG/HDL-C） discriminated IR better than other indexes for both sexes; areas under the receiver operating characteristic （ROC） curves （AUC） values were 0.770 （95％ confidence interval 0.733-0.807） and 0.772 （0.736-0.809）,respectively,for women and 0.754 （0.664-0.844）and 0.756 （0.672-0.840）,respectively,for men.To identify IR,the optimal cut-offs for TG and TG/HDL-C ratio were 1.315 mmol/L （sensitivity 74.3％,specificity 71.0％） and 0.873 （sensitivity 70.1％,specificity 73.4％）,respectively,for women,and 1.275 mmol/L （sensitivity 66.7％,specificity 74.4％） and 0.812 （sensitivity 75.8％,specificity 69.2％）,respectively,for men.Conclusion TG and TG/HDL-C ratio could be used to identify IR in urban middle-aged and older non-obese Chinese without diabetes.

Apolipoprotein A1,the neglected relative of Apolipoprotein E and its potential role in Alzheimer’s disease

Lipoproteins are multi-molecule assemblies with the primary function of transportation and processing of lipophilic substances within aqueous bodily fluids(blood,cerebrospinal fluid).Nevertheless,they also exert other physiological functions such as immune regulation.In particular,neurons are both sensitive to uncontrolled responses of the immune system and highly dependent on a controlled and sufficient supply of lipids.For this reason,the role of certain lipoproteins and their protein-component(apolipoproteins,Apo’s)in neurological diseases is perceivable.ApoE,for example,is well-accepted as one of the major risk factors for sporadic Alzheimer’s disease with a protective allele variant(ε2)and a risk-causing allele variant(ε4).ApoA1,the major protein component of high-density lipoproteins,is responsible for transportation of excess cholesterol from peripheral tissues to the liver.The protein is synthesized in the liver and intestine but also can enter the brain via the choroid plexus and thereby might have an impact on brain lipid homeostasis.This review focuses on the role of ApoA1 in Alzheimer’s disease and discusses whether its role within this neurodegenerative disorder is specific or represents a general neuroprotective mechanism.

Coexistence of High Fibrinogen and Low High-density Lipoprotein Cholesterol Levels Predicts Recurrent Cerebral Venous Thrombosis

Background： Cerebral venous thrombosis （CVT） may lead to serious neurological disorders; however, little is known about the risk factors for recurrent CVT. Our aim was to determine the association between elevated fibrinogen and decreased high-density lipoprotein cholesterol （HDL-C） levels with recurrent CVT. Methods： This retrospective cohort study included participants if they had a first episode of objectively defined CVT and were admitted to Xuan Wu Hospital, Capital Medical University from August 2005 to September 2009. Demographic and clinical variables were collected, as well as laboratory parameters, inchiding plasma fibrinogen and HDL-C. Patients with CVT were tbllowed for recurrent symptomatic CVT. Follow-up was through the end of September 2010. Potential predictors of recurrence were analyzed using Cox survival analysis. Results： At tile end of the lbllow-up, 95 patients were eligible lbr the study. Twelve of 95 patients （12.6%） had recurred CVT. Tile median time of recurrence was 7 months （range： 1-39 months）. Eight of these 12 （66.7%） experienced rectirrence within the first 12 months alter their initial CVT. The recurrence rate of CVT was 2.76 per 100 patient-years. Multivariate Cox regression analysis demonstrated that the coexistence of high fibrinogen （〉4.00 g/L） and low HDL-C （〈1.08 mmol/L） levels at baseline was the only independent predictor for recurrent CVT （hazard ratio： 4.69; 95% confidence interval： 1.10-20,11; P 〈 0.05）. Of tile twelve patients with recurrent CVT in our study, 7 （58.3%） had high fibrinogen plus low HDL-C levels. All 7 of these patients took warfarin for 3-12 months, and 6 of 7 had rectirrent CVT after the discontinuation of anticoagulant treatment. Conclusions： Concomitant high fibrinogen and low HDL-C levels may be associated with recurrence of CVT. The ett＇ect of potential risk lhctors related to atherothrombosis on rectinent CVT should be closely monitored.

Predictive and Prognostic Value of High-density Lipoprotein Cholesterol in Young Male Patients with Acute Myocardial Infarction

Background： The level of high-density lipoprotein cholesterol （HDL-C） is an important risk indicator and used in risk factor counting and quantitative risk assessment; however, the effect of HDL-C in young male patients with acute myocardial infarction （AMI） is unclear. The aim of this study was to investigate the effect of HDL-C in young male patients. Methods： We recruited 267 consecutive young male patients （≤44 years） diagnosed with AMI. Other 247 participants free from coronary heart disease were enrolled as controls. HDL-C levels of AMI patients and controls were evaluated to analyze the predictive value on AMI. According to the cutoff point of 1.04 mmol/L HDL-C, patients of AMI were divided into two subgroups （normal HDL-C group and low HDL-C group） and were followed up for 2 years. Clinical end points included all major adverse coronary events （MACEs）： the main cause of death, nonfatal myocardial infarction, readmissions for acute coronary syndrome, arrhythmias, or revascularization. The prognostic value of HDL-C was evaluated using Cox regression according to MACE. Results： Patients of AMI had decreased proportion in normal HDL-C group compared to controls （47.2% vs. 57.9%; P = 0.017）. Logistic regression analysis showed that there was an inverse relationship between HDL-C and AMI in young males. In the low HDL-C subgroup of AMI patients （n = 141）, 34 （24.1%） patients experienced a MACE during the 2-year follow-up, compared with 15 （11.9%） patients in normal HDL-C subgroup （n = 126）. The Cox regression analysis showed that HDL-C was an independent predictor of a MACE during the follow-up period （hazard ratio = 0.354, P = 0.006）. Conclusion： HDL-C was an important parameter for predicting the risk and the clinical outcomes of AMI in young male patients.

EXPERIMENTAL STUDY ON THE PREVENTION AND TREATMENT EFFECT OF WARMING-REINFORCING METHOD ON RABBIT'S HYPERLIPEMIA

In this experiment, the contents of serum total cholesterol (TC), triglyceride(TG),low-density lipoprotein(LDL), high-density lipoprotein(HDL) were used as indexes to observe the effects of warming-reinforcing method on rabbit’s lipide, liopoprotein. The results indicated that in the warming-reinforcing group, TC decreased markedly and HDL increased obviously with significant difference as compared with the twirling-reinforcing group:TC and LDL also decreased, but no significant differencte as compared with the twirling-reinforcing group. Warming-reinforcing method can decrease lipids more effectively than twirling-reinforcing method.

Effectiveness of health coaching on diabetic patients: A systematic review and meta-analysis

、Background:Using health coaching to improve the quality of life and health outcomes of the patients with diabetes mellitus,has emerged as a possible intervention.However,the few published randomized controlled trials using health coaching for patients with diabetes mellitus have reported mixed results.The present meta-analysis aimed to determine the effectiveness of health coaching on modifying health status and quality of life among diabetic patients and to clarify the characteristics of coaching delivery that make it most effective.Methods:This study searched for articles on randomized controlled trials of health coaching interventions targeting type 2 diabetic patients that were published in the English language from January 2005 through December 2018 in the Cochrane,Medline,PubMed,Trip,and Embase databases.Patients in the control group received usual diabetes mellitus care,and those in the experimental group received health coaching based on usual diabetes mellitus care.The primary outcomes included Hemoglobin A1c(HbA1c)and cardiovascular disease risk factors,including systolic blood pressure,diastolic blood pressure,triglyceride,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol,total cholesterol,and body weight.The secondary outcomes included quality of life,self-efficacy,self-care skills,and psychological outcomes.Results:Health coaching intervention has a significant effect on HbA1c[mean difference(MD)=-0.35,confidence interval(CI)=-0.47,-0.22,I2=83%,P<0.001]and HDL-C(MD=-0.50,CI=-0.93,-0.07,I2=10%,P=0.02).The most effective strategy for health coaching delivery associated with improvement of HbA1c was decreasing the number of sessions and increasing the duration of each session.However,no significant difference was found for weight,SBP,diastolic blood pressure,triglyceride,low-density lipoprotein cholesterol,or total cholesterol.Mixed results were reported for the effect of health coaching on quality of life,self-efficacy,self-care skills,and depressive symptoms outcome.Conclusion:Health coaching intervention has a significant effect on HbA1c and HDL-C,and the most effective strategy is decreasing the number of sessions while increasing session duration.However,these results should be interpreted with caution as the evidence comes from studies at some risk of bias with considerable heterogeneity and imprecision.

Novel parameter based on lipid indicators ratio improves prognostic value of plasma lipid levels in resectable colorectal cancer patients

BACKGROUND At present,the value of lipid indicators in evaluating the prognosis of colorectal cancer is still relatively limited.AIM To evaluate the value of a novel parameter for colorectal cancer(CRC)prognosis scoring based on preoperative serum lipid levels.METHODS Four key serum lipid factors,namely,high-density lipoprotein cholesterol(HDLC),low-density lipoprotein cholesterol(LDL-C),apolipoprotein A1(Apo A1),and apolipoprotein B(Apo B),were detected.Two representative ratios,HDL-C-LDLC ratio(HLR)and Apo A1-Apo B ratio(ABR)were calculated.The relationship of these parameters with the prognosis of CRC patients including progression-free survival(PFS)and overall survival(OS)was analyzed by Kaplan-Meier plot and Cox proportional hazards regression.A novel lipoprotein cholesterol-apolipoprotein(LA)score based on HLR and ABR was established and its value in prognosis evaluation for CRC patients was explored.RESULTS Multivariate Cox proportional hazards regression analysis of PFS and OS showed that HDL-C,Apo A1,HLR,and ABR were positively associated with the prognosis of CRC patients.LA score was independently associated with a good prognosis in resectable CRC patients.Data processing of a dummy variable showed that the prognosis of patients with higher LA scores is better than that with lower LA scores.CONCLUSION The newly established LA score might serve as a better predictor of the prognosis of resectable CRC patients.

ANALYSIS OF SERUM LIPIDS IN PSORIASIS

Serum lipids were determined in 100 psoriatics and the results indicated (1) the incidences of hypercholesterolemia (9%) and hypertriglyceridemia (17%) in psoriatics were significantly higher than in controls; (2) the mean values of serum TC, LDL-C and TC/HDL-C in psoriatics were significantly higher as compared with normal healthy controls matched for sex and age; (3) serum TC, LDL-C and TG values were significantly higher in cases whose disease was progressive or whose lesions involved more than 20% of body surface area than in cases whose disease stationary or lesions less than 20%. As the incidences of hypertension and coronary heart disease were also significantly higher in psoriatics than in controls, the authors proposed that some integrated relationship would exist.

Baseline HDL-C/apolipoprotein A-I ratio predicts the severity of coronary artery lesions in diabetic patients with acute coronary syndrome

Background A low high-density lipoprotein cholesterol(HDL-C)to apolipoprotein A-I(apo A-I)ratio which reflects a small HDL-C particle size is emerging as an important predictor of cardiovascular risks.This study aimed to determine the association of HDL-C/apo A-I ratio with the severity of coronary artery lesions in diabetic patients.Methods Observational study was conducted and 478 diabetic patients with acute coronary syndrome(ACS)were enrolled.Baseline serum levels of HDL-C,apo A-I,clinical and biochemical parameters were collected.All patients underwent coronary angiography to evaluate the severity of coronary artery disease(CAD)in terms of the number of stenotic coronary arteries(defined as a stenosis≥50%)and the calculated Gensini score.Patients were then divided into different subgroups according to the two categories:single-,double-or triple-vessel groups;and Gensini Score groups(lower≤4,middle:5-15,and upper≥16).Receiver operating characteristic curves(ROC)were conducted to evaluate the diagnostic values in identifying severe CAD lesions.The association between HDL-C/apo A-I ratio and CAD severity was determined by multivariate logistic regression analysis.Results Patients with triple-vessel lesions or upper Gensini score had more CAD risk factors such as older age,smoking,low HDL-C and elevated fasting blood glucose(FBG).A lower HDL-C/apo A-I ratio corresponded to more vessels stenoses and a higher Gensini score.Notably,HDL-C/apo A-I outperformed HDL-C or apo A-I alone in diagnosing severe CAD lesions in ROC analyses.Moreover,multivariate regression analyses revealed that after adjustment for traditional risk factors such as LDL-C,FBG and HAb1c,HDL-C/apo A-I ratio remained independently associated with the severity of CAD in diabetic patients with ACS(all P<0.05).Conclusions HDL-C/apo A-I may be a useful indicator for the severity of CAD in diabetic patients with ACS.

New insights into the regulation of cholesterol eft from the sperm membrane

Cholesterol is an essential component of the mammalian plasma membrane because it promotes membrane stability without comprising membrane fluidity. Given this important cellular role, cholesterol levels are tightly controlled at multiple levels. It has been clearly shown that cholesterol redistribution and depletion from the sperm membrane is a key part of the spermatozoon＇s preparation for fertilization. Some factors that regulate these events are described （e.g., bicarbonate, calcium） but the mechanisms underlying cholesterol export are poorly understood. How does a hydrophobic cholesterol molecule inserted in the sperm plasma membrane enter the energetically unfavorable aqueous surroundings？ This review will provide an overview of knowledge in this area and highlight our gaps in understanding. The overall aim is to better understand cholesterol redistribution in the sperm plasma membrane, its relation to the possible activation of a cholesterol transporter and the role of cholesterol acceptors. Armed with such knowledlze, sl）erm handlin~ techniques can be adapted to better prepare spermatozoa for in vitro and in vivo fertilization.

Hypolipidemic and anti-atherosclerogenic effects of aqueous extract of Ipomoea batatas leaves in diet-induced hypercholesterolemic rats

Objective:Ipomoea batatas(L.)Lam.is a food plant used in African traditional medicine to treat cardiovascular diseases and related conditions.We assessed the hypolipidemic and anti-atherosclerogenic properties of the aqueous extract of I.batatas leaves in a rat model of diet-induced hypercholesterolemia.Methods:Hypercholesterolemia was induced in male Wistar rats by exclusive feeding with a cholesterolenriched(1%)standard diet for four weeks.Then,rats were treated once daily(per os)with I.batatas extract at doses of 400,500 and 600 mg/kg or with atorvastatin(2 mg/kg),for four weeks.Following treatment,animals were observed for another four weeks and then sacrificed.Aortas were excised and processed for histopathological studies,and blood glucose level and lipid profile were measured.Results:Hypercholesterolemic animals experienced a 21.5%faster increase in body weight,significant increases in blood glucose and blood lipids(148.94%triglycerides,196.97%high-density lipoprotein cholesterol,773.04%low-density lipoprotein cholesterol,148.93%very low-density lipoprotein cholesterol and 210.42%total cholesterol),and increases in aorta thickness and atherosclerotic plaque sizes compared to rats fed standard diet.Treatment of hypercholesterolemic rats with the extract mitigated these alterations and restored blood glucose and blood lipid levels to normocholesterolemic values.Conclusion:Our findings suggest that I.batatas leaves have hypolipidemic and anti-atherosclerogenic properties and justify their use in traditional medicine.

Early testing of insulin resistance: a tale of two lipid ratios in a group of 5th graders screened by the Coronary Artery Risk Detection in Appalachian Communities Project (CARDIAC Project)

Background In West Virginia (WV),47% of fifth-grade children are either overweight or obese.There is no clear consensus regarding the definition of insulin resistance in children,and directly measuring insulin on the population level is costly.Two proposed measures examined further in this study include triglyceride (TRIG)/high-density lipoprotein cholesterol (HDL-C) ratio and TRIG/low-density lipoprotein (LDL-C) ratio.The purpose of this study is to examine the relationship between TRIG/HDL-C ratio,TRIG/LDL-C ratio and insulin resistance in fifth-graders with acanthosis nigricans (AN).Methods Between 2007 and 2016,52,545 fifth-grade students in WV were assessed for AN.Fasting glucose and insulin levels were collected only for a sub-group of students who were AN-positive and was used to determine insulin resistance using the Homeostatic Model for Insulin Resistance (HOMA-IR) equation.Statistical analysis included t tests and logistic regression with receiver operating characteristic curves.Results Of the students assessed for AN,4.5% (n =2360) tested positive.The prevalence of insulin resistance was 79% (n =814) among 1030 with AN and complete HOMA-IR.TRIG/HDL-C ratio and TRIG/LDL-C ratio were significantly associated with insulin resistance (TRIG/HDL-C:Est.=0.36,P < 0.0001,AUC =0.68;TRIG/LDL-C:Est.=0.87,P < 0.0001,AUC =0.69).Multivariate analysis showed that increased body mass index (Est.=0.05,P < 0.0001),gender (Est.=0.49,p < 0.0001) and TRIG/HDL-C ratio (Est.=0.21,P < 0.0001) were significantly associated with insulin resistance.Conclusions TRIG/HDL-C is a better surrogate marker of insulin resistance in AN-positive children compared to TRIG/ LDL-C ratio;so,on a population-level,cholesterol rather than insulin may be obtained for preliminary testing of early insulin resistance in children.