Association between sensitivity to thyroid hormones and non-highdensity lipoprotein cholesterol levels in patients with type 2 diabetes mellitus

BACKGROUND Dyslipidemia and type 2 diabetes mellitus(T2DM)are chronic conditions with substantial public health implications.Effective management of lipid metabolism in patients with T2DM is critical.However,there has been insufficient attention given to the relationship between thyroid hormone sensitivity and dyslipidemia in the T2DM population,particularly concerning non-high-density lipoprotein cholesterol(non-HDL-C).AIM To clarify the association between thyroid hormone sensitivity and dyslipidemia in patients with T2DM.METHODS In this cross-sectional study,thyroid hormone sensitivity indices,the thyroid feedback quantile-based index(TFQI),the thyroid-stimulating hormone index(TSHI),the thyrotrophic T4 resistance index(TT4RI),and the free triiodothyronine(FT3)/free thyroxine(FT4)ratio were calculated.Logistic regression analysis was performed to determine the associations between those composite indices and non-HDL-C levels.Random forest variable importance and Shapley Additive Explanations(SHAP)summary plots were used to identify the strength and direction of the association between hyper-non-HDL-C and its major predictor.RESULTS Among the 994 participants,389(39.13%)had high non-HDL-C levels.Logistic regression analysis revealed that the risk of hyper-non-HDL-C was positively correlated with the TFQI(OR:1.584;95%CI:1.088-2.304;P=0.016),TSHI(OR:1.238;95%CI:1.034-1.482;P=0.02),and TT4RI(OR:1.075;95%CI:1.006-1.149;P=0.032)but was not significantly correlated with the FT3/FT4 ratio.The relationships between composite indices of the thyroid system and non-HDL-C levels differed according to sex.An increased risk of hyper-non-HDL-C was associated with elevated TSHI levels in men(OR:1.331;95%CI:1.003-1.766;P=0.048)but elevated TFQI levels in women(OR:2.337;95%CI:1.4-3.901;P=0.001).Among the analyzed variables,the average SHAP values were highest for TSHI,followed by TT4RI.CONCLUSION Impaired sensitivity to thyroid hormones was associated with high non-HDL-C levels in patients with T2DM.

Association between Low-density Lipoprotein Receptor-related Protein 5 Polymorphisms and Type 2 Diabetes Mellitus in Han Chinese:a Case-control Study

Objective To investigate the association between low-density lipoprotein receptor-related protein 5 （LRPS） variants （rs12363572 and rs4930588） and type 2 diabetes mellitus （T2DM） in Han Chinese. Methods A total of 1842 T2DM cases （507 newly diagnosed cases and 1335 previously diagnosed cases） and 7777 controls were included in this case-control study. PCR-RFLP was conducted to detect the genotype of the two single nucleotide polymorphisms （SNPs）. Odds ratios （ORs） and 95% confidence intervals （95% CIs） were calculated to describe the strength of the association by logistic regression. Results In the study subjects, neither rs12363572 nor rs4930588 was significantly associated with T2DM, even after adjusting for relevant covariates. When stratified by body mass index （BMI）, the two SNPs were also not associated with T2DM. Among the 3 common haplotypes, only haplotype ~ was associated with reduced risk of T2DM （OR 0.820, 95% CI 0.732-0.919）. In addition, rs12363572 was associated with BMI （P〈0.001） and rs4930588 was associated with triglyceride levels （P=0.043） in 507 newly diagnosed T2DM cases but not in healthy controls. Conclusion No LRP5 variant was found to be associated with T2DM in Han Chinese, but haplotype TT was found to be associated with T2DM.

Prevalence of High Non-high-density Lipoprotein Cholesterol and Associated Risk Factors in Patients with Diabetes Mellitus in Jilin Province,China:A Cross-sectional Study

Dyslipidemia is a risk factor for cardiovascular diseases（CVDs）in patients with diabetes,and non-high-density lipoprotein cholesterol（non-HDL-C）is a better predictor of CVDs than low-density lipoprotein cholesterol（LDL-C）in patients with diabetes.Therefore,we aimed to investigate the distribution of non-HDL-C and the prevalence of high non-HDL-C level in Chinese patients with diabetes mellitus and identify the

Editorial on hemoglobin A1c, blood pressure, and lowdensity lipoprotein cholesterol goals in diabetics

The American Diabetes Association (ADA) 2013 guidelines state that a reasonable hemoglobin A1c goal for many nonpregnant adults with diabetes is less than 7.0% a hemoglobin A1c level of less than 6.5% may be considered in adults with short duration of diabetes, long life expectancy, and no significant cardiovascular disease if this can be achieved without significant hypoglycemia or other adverse effects of treatment. A hemoglobin A1c level less than 8.0% may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced macrovascular and microvascular complications, extensive comorbidities, and long-standing diabetes in whom the hemoglobin A1c goal is difficult to attain despite multiple glucoselowering drugs including insulin. The ADA 2013 guidelines recommend that the systolic blood pressure in most diabetics with hypertension should be reduced to less than 140 mmHg. These guidelines also recommend use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in the treatment of hypertension in diabetics unless they are pregnant. Diabetics at high risk for cardiovascular events should have theirserum low-density lipoprotein (LDL) cholesterol lowered to less than 70 mg/dL with statins. Lower-risk diabetics should have their serum LDL cholesterol reduced to less than 100 mg/dL. Combination therapy of a statin with either a fibrate or niacin has not been shown to provide additional cardiovascular benefit above statin therapy alone and is not recommended. Hypertriglyceridemia should be treated with dietary and lifestyle changes. Severe hypertriglyceridemia should be treated with drug therapy to reduce the risk of acute pancreatitis.

Hepatitis C virus clearance and less liver damage in patients with high cholesterol, low-density lipoprotein cholesterol and APOE ε4 allele

BACKGROUND Cholesterol is related to improvements in the rate of sustained virological response and a robust immune response against the hepatitis C virus(HCV).APOE gene polymorphisms regulate cholesterol levels modifying the course of the HCV infection.The relationship between cholesterol,APOE alleles,and the outcome of HCV infection has not been evaluated in the admixed population of Mexico.AIM To investigate the role of APOE-ε2,-ε3,and-ε4 alleles and the metabolic profile in the outcome of HCV infection.METHODS A total of 299 treatment-na?ve HCV patients were included in this retrospective study.Patients were stratified in chronic hepatitis C(CHC)(n=206)and spontaneous clearance(SC)(n=93).A clinical record was registered.Biochemical tests were assessed by dry chemistry assay.APOE genotypes were determined using a Real-Time polymerase chain reaction assay.RESULTS Total cholesterol,low-density lipoprotein cholesterol(LDL-c),triglycerides,and hypercholesterolemia were higher in SC than CHC patients as well as the frequency of the APOEε4 allele(12.4%vs 7.3%).SC patients were overweight(54.8%).Theε4 allele was associated with SC(OR=0.55,95%CI:0.31-0.98,P=0.042)and mild fibrosis(F1-F2)in CHC patients(OR 0.091,95%CI 0.01-0.75,P=0.020).LDL-c≥101.5 mg/dL(OR=0.20,95%CI:0.10-0.41,P<0.001)and BMI≥26.6 kg/m2(OR=0.37,95%CI:0.18-0.76,P<0.001)were associated with SC status;while ALT≥50.5 IU/L was negatively associated(OR=5.67,95%CI:2.69-11.97,P<0.001).CONCLUSION In SC patients,the APOEε4 allele and LDL-c conferred a protective effect in the course of the HCV infection in the context of excess body weight.

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.

A Modified Chitosan Adsorbent for Selective Removal of Low Density Lipoprotein

A modified chitosan adsorbent was synthesized through a simple preparation procedure, and it demonstrated good adsorption performance for selective removal of low density lipoprotein in human plasma. Phase inversion technique was employed to form chitosan beads, to which epoxy groups were then introduced by reacting with ethyleneglycol diglycidylether, and tryptophan was subsequently coupled to the epoxy-activated beads.

Effects of Oxidized Low Density Lipoprotein onthe Expression and Function of ABCA1 in Macrophages

Summary:In the present study, we examined the regulation of the expression and function of ABCA1 by modified LDL (ox-LDL) in vitro. After incubation with apoA-I for 24 h, RAW264.7 cells effluxed 37.65 % cholesterol loaded by acetyl LDL (ac-LDL), and 9.78 % cholesterol in ox-LDL group. The level of ABCA1 mRNA increased about three times either when cells were incubated with 100 μg /mL ac-LDL or with 100 μg /mL ox-LDL. However, the level of ABCA1 protein rose by 1.57 times in ac-LDL group and 1.26 times in ox-LDL group. These results demonstrated that ox-LDL had different effect on the expression and function of ABCA1, ox-LDL might decrease the cholesterol efflux mediated by ABCA1 through other unknown mechanisms.

Inhibition of Oxidative Modification of Human Low Density Lipoprotein by Resveratrol

To further investigate whether resveratrol, a polyphenolic compound in red wine, affects the oxidation of human low density lipoprotein (LDL), LDL purified from normolipidemic subjects was subjected to Cu\+\{2+\}induced or azo compoundinitiated oxidative modification. The extent of LDL modification was assessed by measuring the formation of thiobarbituric acid reactive substances (TBARS) and the relative electrophoretic mobilities (REM) of LDL. Resveratrol (50 mol/L) reduced TBARS and REM of LDL during Cu\+\{2+\}induced oxidation by 70.5% and 42.3%, respectively (P<0.01), and prolonged the lag phase associated with the oxidative modification of LDL by copper ion or azo compound. These in vitro results suggest that resveratrol may afford LDL protection against oxidative modification, possibly by acting as a free radical scavenger.

Risk factors for low high-density lipoprotein among Asian Indians in the United States

AIM To examine the differences in metabolic risk factors(RFs) by gender in the Asian Indian(AI) population in the United States. METHODS Using cross-sectional data from 1038 randomly selected Asian Indians, we investigated the relationship between metabolic syndrome(Met S) RFs, cardiovascular disease,and diabetes. RESULTS A greater percent of women in this group had increased waist circumference and low high density lipoprotein(HDL) levels than men, but AI males had increased blood glucose, increased blood pressure, and increased triglycerides compared to females. Those individuals who met the Met S criteria had increased cardiovascular disease. One of the biggest single RFs for cardiovascular disease and diabetes reported in the literature for AIs is low HDL. CONCLUSION Our results show that lack of knowledge about diabetes, low physical activity, increased body mass index, and age were the factors most significantly correlated with low HDL in this population. Future studies and prospective trials are needed to further elucidate causes of the Met S and diabetes in AIs.

The rate of patients at high risk for cardiovascular disease with an optimal low-density cholesterol level: a multicenter study from Thailand

Background Hypercholesterolemia is a major risk factor for cardiovascular events in patients with established atherosclerotic disease (EAD) and in those with multiple risk factors (MRFs). This study aimed to investigate the rate of optimal low-density lipoprotein (LDL) cholesterol level in a multicenter registry of patients at high risk for cardiovascular events. Methods A multicenter registry of EAD and MRF patients was conducted. Demographic data,medical history,cardiovascular risk factors,anthropometric data,laboratory data,and medications were recorded and analyzed. We classified patients according to target LDL levels based on recommendation by the European Society of Cardiology (ESC) 2011 into Group 1 which is EAD and diabetes or chronic kidney disease (CKD)–target LDL below 70 mg/dL,and Group 2 which is MRF without diabetes or CKD–target LDL below 100 mg/dL. The rate of optimal LDL level in patients with Group 1 and Group 2 was analyzed and stratified according to the treatment pattern of lipid-lowering medications. Results A total of 3100 patients were included. Of those,51.7% were male. Average age was 65.8 ± 9.7 years. Average LDL level was 96.3 ± 32.6 mg/dL. A vast majority (92.7%) received statin and 9.3% received ezetimibe. Optimal LDL level was achieved in 20.3% of patients in Group 1 (LDL < 70 mg/dL),and in 46.6% in Group 2 (LDL < 100 mg/dL). The overall rate of optimal LDL control was 23% since 89.6% of study population belongs to Group 1. The rate of optimal LDL was not different between high and low potency statin. Factors that were associated with optimal LDL control were older age,the presence of coronary artery disease or peripheral artery disease. Conclusions The rates of optimal LDL level were unacceptably low in this study population. As such,a strategy to improve LDL control in high-risk population should be implemented.

New predictors of in-stent restenosis in patients with diabetes mellitus undergoing percutaneous coronary intervention with drug-eluting stent

Background Percutaneous coronary intervention （PCI） had become the major therapeutic procedure for coronary artery disease （CAD）, but the high rate of in-stent restenosis （ISR） still remained an unsolved clinical problem in clinical practice. Increasing evidences suggested that diabetes mellitus （DM） was a major risk factor for ISR, but the risk predictors of ISR in CAD patients with DM had not been well characterized. The aim of this study was to investigate the clinical and angiographic characteristic predictors significantly associated with the occurrence of ISR in diabetic patients following coronary stenting with drug-eluting stent （DES）. Methods A total of 920 patients with diabetes who diagnosed CAD and underwent coronary DES implantation at Beijing Anzhen Hospital in China were consecutively enrolled from January 2012 to December 2012. Of these, 440 patients underwent the second angiography within ≥ 6 months due to the progression of treated target lesions. Finally, 368 of these patients who met the inclusion and exclusion criteria were followed up by angiography after baseline PCI. According to whether ISR was detected at follow-up angiography, patients were divided into the ISR group （n = 74） and the non-ISR group （n = 294）. The independent predictors of ISR in patients with DM were explored by multivariate Cox＇s proportional hazards regression models. Results A total of 368 patients （260 women and 108 men） with a mean ages of 58.71 ± 10.25 years were finally enrolled in this study. Of these, ISR occurred in 74/368 diabetic patients （20.11%） by follow-up angiography. Univariate analysis showed that most baseline characteristics of the ISR and non-ISR group were similar. Patients in the ISR group had significantly higher serum very low density lipoprotein cholesterol （VLDL-C）, triglyceride （TG） and uric acid （UA） levels, more numbers of target vessel lesions, higher prevalence of multi-vessel disease, higher SYNTAX score, higher rate of previous but lower rate of drinking compared with patients in the non-ISR group. The independent predictors of ISR in patients with DM after DES implantation included VLDL-C （HR = 1.85, 95% CI： 1.24-2.77, P = 0.002）, UA （per 50 μmol/L increments, HR = 1.19, 95% CI： 1.05 1.34, P = 0.006）, SYNTAX score （per 5 increments, HR = 1.34, 95% CI： 1.03-1.74, P = 0.031） and the history ofPCI （HR = 3.43, 95% CI： 1.57-7.80, P = 0.003） by the multivariate Cox＇s proportional hazards regression analysis. Conclusions The increased serum VLDL-C and UA level, higher SYNTAX score and the history of previous PCI were independent predictors of ISR in patients with DM after coronary DES implantation. It provided new evidence for physi- cians to take measures to lower the risk oflSR for the better management of diabetic patients after PCI.

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.

Situational Analysis of Low-density Lipoprotein Cholesterol Control and the Use of Statin Therapy in Diabetes Patients Treated in Community Hospitals in Nanjing, China

Background：Comprehensive management of diabetes should include management of its comorbid conditions,especially cardiovascular complications,which are the leading cause of morbidity and mortality among patients with diabetes.Dyslipidemia is a comorbid condition of diabetes and a risk factor for cardiovascular complications.Therefore,lipid level management is a key of managing patients with diabetes successfully.However,it is not clear that how well dyslipidemia is managed in patients with diabetes in local Chinese health-care communities.This study aimed to assess how well low-density lipoprotein cholesterol （LDL-C） was managed in Nanjing community hospitals,China.Methods：We reviewed clinical records of 7364 diabetic patients who were treated in eleven community hospitals in Nanjing from October 2005 to October 2014.Information regarding LDL-C level,cardiovascular risk factors,and use of lipid-lowering agents were collected.Results：In patients without history of cardiovascular disease （CVD）,92.1% had one or more CVD risk factors,and the most common CVD risk factor was dyslipidemia.The overall average LDL-C level was 2.80 ± 0.88 mmol/L,which was 2.62 ± 0.90 mmol/L and 2.82 ± 0.87 mmol/L in patients with and without CVD history respectively.Only 38% of all patients met the target goal and 37.3% of patients who took lipid-lowering agents met target goal.Overall,24.5% of all patients were on lipid-lowering medication,and 36.3% of patients with a CVD history and 20.9% of patients without CVD history took statins for LDL-C management.The mean statin dosage was 13.9 ± 8.9 mg.Conclusions：Only a small portion of patients achieved target LDL-C level,and the rate of using statins to control LDL-C was low.Managing LDL-C with statins in patients with diabetes should be promoted,especially in patients without a CVD history and with one or more CVD risk factors.

非常规血脂指标在2型糖尿病患者心血管风险评估中的应用进展

动脉粥样硬化性血脂异常与心血管疾病的发病率和死亡率之间的残余风险密切相关,即使2型糖尿病(T2DM)患者的低密度脂蛋白胆固醇(LDL-C)水平达标后,这种风险依然存在。非常规血脂指标[如非高密度脂蛋白胆固醇(HDL-C)、三酰甘油/HDL-C比值、LDL-C/HDL-C比值、总胆固醇/HDL-C比值]在T2DM患者的心血管风险预测中逐渐受到重视。心血管风险的早期识别对于优化T2DM管理至关重要。随着心血管疾病预防策略的不断细化,研究的重点逐渐转向简便、全面且有效的心血管疾病风险分层方法。未来将进一步评估上述指标与其他代谢参数的协同作用,精确区分阈值,优化个体化治疗,并通过动态监测上述指标加强精准的心血管风险管理。

Regulation and deregulation of cholesterol homeostasis: The liver as a metabolic "power station"

Cholesterol plays several structural and metabolic roles that are vital for human biology. It spreads along the entire plasma membrane of the cell, modulating fluidity and concentrating in specialized sphingolipid-rich domains called rafts and caveolae. Cholesterol is also a substrate for steroid hormones. However, too much cholesterol can lead to pathological pictures such as atherosclerosis, which is a consequence of the accumu- lation of cholesterol into the cells of the artery wall. The liver is considered to be the metabolic power station of mammalians, where cholesterol homeostasis relies on an intricate network of cellular processes whose deregulations can lead to several life-threatening pathologies, such as familial and age-related hypercholesterolemia. Cholesterol homeostasis maintenance is carried out by: biosynthesis, via 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity; uptake, through low density lipoprotein receptors (LDLr); lipoprotein release in the blood; storage by esterification; and degradation and conversion into bile acids. Both HMGR and LDLr are transcribed as a function of cellular sterol amount by a family of transcription factors called sterol regulatory element binding proteins that are responsible for the maintenance of cholesterol homeostasis through an intricate mechanism of regulation. Cholesterol obtained by hepatic de novo synthesis can be esterified and incorporated into apolipoprotein B-100-containing very low density lipoproteins, which are then secreted into the bloodstream for transport to peripheral tissues. Moreover, dietary cholesterol is transferred from the intestine to the liver by high density lipoproteins (HDLs); all HDL particles are internalized in the liver, interacting with the hepatic scavenger receptor (SR-B1). Here we provide an updated overview of liver cholesterol metabolism regulation and deregulation and the causes of cholesterol metabolism-related diseases. Moreover, current pharmacological treatment and novel hypocho-lesterolemic strategies will also be introduced.

Elevated Levels of Very Low？density Lipoprotein Cholesterol Independently Associated with In？stent Restenosis in Diabetic Patients after Drug？eluting Stent Implantation

Background： High rate of in-stent restenosis （ISR） remained an unsolved clinical problem in clinical practice, especially among patients with diabetes mellitus （DM）. Diabetic patients often had hypertriglyceridemia with elevated levels of very low-density lipoprotein cholesterol （VLDL-C）. Increasing evidence suggested that VLDL-C was known as a significant risk factor for atherosclerosis and had been recommended as a treatment target by current dyslipidemia guidelines. However, the role of VLDL-C in the occurrence and development of ISR in coronary artery disease （CAD） patients with DM had not been studied. The aim of this study was to evaluate the association between the elevated levels of VLDL-C and the risk of ISR in CAD patients with DM. Methods： A total of 1390 diabetic patients, who underwent coronary drug-eluting stent （DES） implantation at Beijing Anzhen Hospital and followed up by angiography within 6–24 months, were consecutively enrolled. Patients＇ demographic and clinical characteristics, including age, gender, CAD risk factors, family history, life style, medical history, and coronary angiographic information, were collected carefully at baseline percutaneous coronary intervention and follow-up angiography. Multivariate Cox＆#39;s proportional hazards regression modeling using the step-wise method （entry, 0.05; removal, 0.05） was used to determine the independent risk associated with ISR in diabetic patients. Results： Finally, 1206 of patients were included in this study. ISR occurred in 132/1206 diabetic patients （10.9%） by follow-up angiography. Patients with ISR had elevated median serum VLDL-C levels compared with those without ISR （0.65 mmol/L vs. 0.52 mmol/L, P = 0.030）. The multivariate regression analysis showed that VLDL-C was significantly associated with the risk of ISR in diabetic CAD patients （hazard ratio [HR] = 1.15, 95% confidence interval [CI]： 1.03–1.29, P = 0.017）. The HR for the risk of ISR associated with VLDL-C level ≥0.52 mmol/L was 3.01 （95% CI： 1.24–7.34, P = 0.015）. Conclusion： The elevated level of serum VLDL-C was a significant and independent risk factor for ISR in diabetic CAD patients after coronary DES implantation.

Differential impact of aging and gender on lipid and lipoprotein profiles in a cohort of healthy Chinese Singaporeans

Aim： To evaluate the impact of age and gender on lipid and lipoprotein profiles and the burden of dyslipidemia in a cohort of healthy Chinese Singaporean. Methods： A total of 1 775 healthy Chinese, 536 men and 1 239 women aged between 30 and 70 years old were involved in the present study. Results： Gender differences in all lipid and lipoprotein levels were clearly evident. Singaporean Chinese men have significantly higher levels of total cholesterol （TC）, triglyceride （TG）, low density lipoprotein-cholesterol （LDL-C） and total cholesterol/high density lipoprotein-cholesterol （TC/HDL-C）, and lower levels of HDL-C than women. Although lipid and lipoprotein levels in men did not change in the different age groups, those in women, especially TC, LDL-C and TC/HDL-C, were significantly higher in older women （〉 50 years old） than corresponding levels in younger women （30-46 years old）. Furthermore, TG was significantly correlated with lipids and lipoproteins differently in men and women. If 100 mg/dL of LDL-C were to be adopted as the therapeutic cut-off level, then the burden of care will be huge as approximately 90% of both Chinese men and women have LDL-C greater than 100 mg/dL. Condusion： In light of the findings of the present study, we suggest that preventive measures to promote the reduction in risk of coronary heart disease （CHD） must address the high proportion of men and women with high LDL-C, and that these measures should take into account both the gender and age factors. For men, reduction of high cholesterol must start early in life, whereas for women, steps must be taken earlier to mitigate the anticipated sharp increase in risk, especially after menopause.

Effect of Gengnianchun Recipe (更年春方) on Bone Mineral Density, Bone Biomechanical Parameters and Serum Lipid Level in Ovariectomized Rats

Objective： To observe the effect of Gengnianchun Recipe （更年春方, GNC） on bone mineral density （BMD）, bone biomechanical parameters and serum lipid level in the bilaterally ovariectomized （OVX） rats and to explore the prophylactic and therapeutic action of GNC on ovariectomy induced osteoporosis and hyperlipidemia. Methods： OVX SD rats, 10- 12 months old, were divided into different groups and fed with GNC 2 g/d, GNC 1 g/d and Nilestriol 0. 125 mg/week, respectively for 4 months to observe the change of BMD and bone biomechanical parameters of the lumbar vertebrae, and the serum levels of total cholesterol （TO）, triglyceride（TG）, high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C）, and to compare the effect of the two drugs on the morphology of the uterus. Results： There was marked reduction in BMD and biomechanical parameters in lumbar vertebrae （ P〈0. 01 ） and increase of serum TO and LDL-C levels （ P〈0. 01 ） in rats after OVX. GNC or Nilestriol significantly improved the decreased BMD and biomechanical parameters of the lumbar vertebrae （ P〈0.05 or P〈0. 01 ）, and reduced the serum TO and LDL-C levels （ P〈0. 01 ）. In the Nilestriol group, the wet weight of uterus got increased obviously （ P〈0.01 ）, the number of uterine glands increased, uterine columnar epithelium thickened, and the mitotic figures in the epithelial stroma and myointimal cells augmented. But no such effect in wet weight and morphology of uterus was found in the GNC group. Conclusion： GNC could increase the BMD and biomechanical parameters of the lumbar vertebrae, reduce the serum TO and LDL-C levels, yet produce no adverse reaction in stimulating proliferation and hypertrophy of uterus.

Cholesterol metabolism in cholestatic liver disease and liver transplantation:From molecular mechanisms to clinical implications

The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein(LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X(Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers- such as cholesterol precursor sterols, plant sterols, and cholestanol- may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation.