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 ex...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.展开更多
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 patient...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.展开更多
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(D...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.展开更多
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 cho...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.展开更多
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 withou...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.展开更多
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 withou...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)展开更多
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...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.展开更多
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 an...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.展开更多
目的分析甲状腺结节发生与糖脂代谢水平的相关性。方法选取厦门弘爱医院(2022年1—12月)接受甲状腺检查者100例,根据患者的检查结果不同分组,其中检查结果为甲状腺结节的患者50例为研究组,检查结果为未发生甲状腺结节的患者50例为对照...目的分析甲状腺结节发生与糖脂代谢水平的相关性。方法选取厦门弘爱医院(2022年1—12月)接受甲状腺检查者100例,根据患者的检查结果不同分组,其中检查结果为甲状腺结节的患者50例为研究组,检查结果为未发生甲状腺结节的患者50例为对照组。分析患者的基础资料,明确甲状腺结节发生与糖脂代谢水平[空腹血糖(fasting plasma glucose,FPG)、总胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)及高密度脂蛋白胆固醇(high density lipid-cholesterol,HDL-C)]的相关性。结果研究组FPG、TC、TG和LDL-C水平较对照组更高,差异有统计学意义(P<0.05)。而在HDL-C指标相比之下,差异无统计学意义(P>0.05)。因FT3、FT4、TSH均有不确定值为等级资料行Spearman秩相关分析。TSH与FPG、TC、LDL-C、HDL-C均呈正相关(r值分别为0.105、0.635、0.143、0.704、0.619,P<0.01),而FT3与FPG、TC、LDL-C、HDL-C均呈负相关(r值分别为-0.568、-0.676、-0.352、-0.702、-0.764,P<0.01),FT4与FPG、TC、LDL-C、HDL-C均呈负相关(r值分别为-0.401、-0.547、-0.425、-0.639、-0.493,P<0.01)。结论血清FPG、TC、TG、LDL-C升高,HDL-C降低,为甲状腺结节诱发因素。展开更多
目的:探讨体检人群甘油三酯/高密度脂蛋白胆固醇(triglyceride/high density lipoprotein cholesterol ratio,TG/HDL-C)、甘油三酯-葡萄糖乘积(riglyceride-glucose index,TyG)指数及其衍生指数水平与白蛋白尿异常的相关性,同时分析TG/H...目的:探讨体检人群甘油三酯/高密度脂蛋白胆固醇(triglyceride/high density lipoprotein cholesterol ratio,TG/HDL-C)、甘油三酯-葡萄糖乘积(riglyceride-glucose index,TyG)指数及其衍生指数水平与白蛋白尿异常的相关性,同时分析TG/HDL-C、TyG以及TyG-BMI(riglyceride-glucose index-body mass index,TyG-BMI)预测白蛋白尿的能力。方法:获取2022年1月至12月体检中心年龄在18岁以上3739例受检者进行回顾性分析,将研究对象分为白蛋白尿异常组(n=841)和对照人群(n=2898),将TG/HDL-C、TyG以及TyG-BMI按四分位数进行分组,采用logistic回归模型分析与体检人群白蛋白尿异常风险之间的关系。采用限制性立方样条回归模型分析不同水平TG/HDL-C、BMI、TyG以及TyG-BMI与白蛋白尿的剂量反应关系。通过受试者工作特征曲线分析单一指标与联合指标对白蛋白尿的预测价值。结果:除平均血红蛋白浓度、高密度脂蛋白胆固醇外,异常组年龄、中性粒细胞、单核细胞、血小板、血白细胞计数、平均红细胞体积、红细胞分布宽度SD、红细胞分布宽度、血小板压积、总蛋白、白蛋白、谷氨酰转肽酶、空腹血糖、糖化血红蛋白、总胆固醇、低密度脂蛋白胆固醇、甘油三酯(triglyceride,TG)、体质指数(body mass index,BMI)、收缩压、舒张压、脉率、碱性磷酸酶、TyG指数、TyG-BMI、TG/HDL-C均高于对照组。调整混杂因素后,逻辑回归结果显示,与第2、第3分位数相比,TG/HDL-C、TyG、TyG-BMI指数第4四分位数组发生风险最高,其分别为1.895倍(95%CI=1.355~2.653)、2.377倍(95%CI=1.657~3.417)、2.319(95%CI=1.666~3.237)。BMI、TyG-BMI指数与白蛋白尿异常呈明显的非线性剂量反应关系,曲线呈近似“U”型,TyG、TG/HDL-C与白蛋白尿异常之间的剂量反应关系呈逐渐递增趋势,曲线呈近似“J”型。受试者工作特征(receiver operating characteristic,ROC)曲线结果显示,TyG-BMI预测能力优于其他3个指标,其AUC值为0.640。除TyG-BMI+TG/HDL-C之外,其余联合预测能力均优于单一预测指标,TyG-BMI+TG/HDL-C+TyG指数预测白蛋白尿的能力最优,AUC为0.6504。结论:TyG指数、TG/HDL-C比值升高与白蛋白尿异常密切相关,均对白蛋白尿具有一定的预测价值。综合考虑,TyG-BMI+TG/HDL-C+TyG指数是较佳白蛋白尿预测联合指标。展开更多
文摘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.
基金supported by National Natural Science Foundation of China(No.81170259)
文摘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.
基金supported by a grant from the Scientific Research Foundation for the Returned Overseas Chinese Scholars by the State Education Ministry of China (No.2005383-6144)
文摘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.
基金Supported by the Austrian Science Fund,No.P20116-B13 and No.P22838-B13
文摘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.
文摘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.
文摘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)
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11504287 and 11774279)
文摘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.
文摘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.
文摘目的分析甲状腺结节发生与糖脂代谢水平的相关性。方法选取厦门弘爱医院(2022年1—12月)接受甲状腺检查者100例,根据患者的检查结果不同分组,其中检查结果为甲状腺结节的患者50例为研究组,检查结果为未发生甲状腺结节的患者50例为对照组。分析患者的基础资料,明确甲状腺结节发生与糖脂代谢水平[空腹血糖(fasting plasma glucose,FPG)、总胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)及高密度脂蛋白胆固醇(high density lipid-cholesterol,HDL-C)]的相关性。结果研究组FPG、TC、TG和LDL-C水平较对照组更高,差异有统计学意义(P<0.05)。而在HDL-C指标相比之下,差异无统计学意义(P>0.05)。因FT3、FT4、TSH均有不确定值为等级资料行Spearman秩相关分析。TSH与FPG、TC、LDL-C、HDL-C均呈正相关(r值分别为0.105、0.635、0.143、0.704、0.619,P<0.01),而FT3与FPG、TC、LDL-C、HDL-C均呈负相关(r值分别为-0.568、-0.676、-0.352、-0.702、-0.764,P<0.01),FT4与FPG、TC、LDL-C、HDL-C均呈负相关(r值分别为-0.401、-0.547、-0.425、-0.639、-0.493,P<0.01)。结论血清FPG、TC、TG、LDL-C升高,HDL-C降低,为甲状腺结节诱发因素。
文摘目的:探讨体检人群甘油三酯/高密度脂蛋白胆固醇(triglyceride/high density lipoprotein cholesterol ratio,TG/HDL-C)、甘油三酯-葡萄糖乘积(riglyceride-glucose index,TyG)指数及其衍生指数水平与白蛋白尿异常的相关性,同时分析TG/HDL-C、TyG以及TyG-BMI(riglyceride-glucose index-body mass index,TyG-BMI)预测白蛋白尿的能力。方法:获取2022年1月至12月体检中心年龄在18岁以上3739例受检者进行回顾性分析,将研究对象分为白蛋白尿异常组(n=841)和对照人群(n=2898),将TG/HDL-C、TyG以及TyG-BMI按四分位数进行分组,采用logistic回归模型分析与体检人群白蛋白尿异常风险之间的关系。采用限制性立方样条回归模型分析不同水平TG/HDL-C、BMI、TyG以及TyG-BMI与白蛋白尿的剂量反应关系。通过受试者工作特征曲线分析单一指标与联合指标对白蛋白尿的预测价值。结果:除平均血红蛋白浓度、高密度脂蛋白胆固醇外,异常组年龄、中性粒细胞、单核细胞、血小板、血白细胞计数、平均红细胞体积、红细胞分布宽度SD、红细胞分布宽度、血小板压积、总蛋白、白蛋白、谷氨酰转肽酶、空腹血糖、糖化血红蛋白、总胆固醇、低密度脂蛋白胆固醇、甘油三酯(triglyceride,TG)、体质指数(body mass index,BMI)、收缩压、舒张压、脉率、碱性磷酸酶、TyG指数、TyG-BMI、TG/HDL-C均高于对照组。调整混杂因素后,逻辑回归结果显示,与第2、第3分位数相比,TG/HDL-C、TyG、TyG-BMI指数第4四分位数组发生风险最高,其分别为1.895倍(95%CI=1.355~2.653)、2.377倍(95%CI=1.657~3.417)、2.319(95%CI=1.666~3.237)。BMI、TyG-BMI指数与白蛋白尿异常呈明显的非线性剂量反应关系,曲线呈近似“U”型,TyG、TG/HDL-C与白蛋白尿异常之间的剂量反应关系呈逐渐递增趋势,曲线呈近似“J”型。受试者工作特征(receiver operating characteristic,ROC)曲线结果显示,TyG-BMI预测能力优于其他3个指标,其AUC值为0.640。除TyG-BMI+TG/HDL-C之外,其余联合预测能力均优于单一预测指标,TyG-BMI+TG/HDL-C+TyG指数预测白蛋白尿的能力最优,AUC为0.6504。结论:TyG指数、TG/HDL-C比值升高与白蛋白尿异常密切相关,均对白蛋白尿具有一定的预测价值。综合考虑,TyG-BMI+TG/HDL-C+TyG指数是较佳白蛋白尿预测联合指标。