Cholesterol Metabolic Markers for Differential Evaluation of Patients with Hyperlipidemia and Familial Hypercholesterolemia.

The cholesterol metabolism in humans can be indirectly reflected by measuring cholesterol metabolism marker levels. We aimed to investigate the association of cholesterol homeostasis markers on standard lipid profiling components in familial hypercholesteremia and hyperlipidemia patients. A total of 69 hyperlipidemia patients, 25 familial hypercholesteremia (FHC) patients, and 64 healthy controls were enrolled in this study. We performed routine testing of blood lipid water. Gas chromatography was used to determine the changes in the concentration of cholesterol synthesis (squalene, desmosterol, and lathosterol) and absorption markers (campesterol, sitosterol, and stigmasterol) in the blood. Baseline hyperlipidemia patients displayed significantly higher total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels in comparison to the control group, which was reflected in the increased levels of squalene, desmosterol, campesterol, and sitosterol observed (P < 0.05) in the hyperlipidemia patients. The desmosterol, lathosterol, campesterol, stigmasterol, and sitosterol were statistically different in the FHC group than the hyperlipidemic group (P < 0.05). The proportions of squalene/cholesterol, lathosterol/cholesterol, stigmasterol/cholesterol, and sitosterol/cholesterol in the FHC group were lower than those in the hyperlipidemic group; only desmosterol/cholesterol was higher than that in the hyperlipidemic group. Correlation studies between lipid metabolic factors showed that the proportion of moderate and strong correlations was much higher in the FHC group than in the other two groups (76.92% vs. 32.50% and 31.25%). Logistic regression analysis showed that the concentrations of glucose, LDL-C, lactosterol, and sitosterol were all independent risk factors for developing hyperlipidemia. This result was further confirmed by the ROC curve. These results indicated that the study of cholesterol synthesis and decomposition markers can serve as a reference index for related diseases caused by changes in its concentration.

Gas Chromatography and Flame-Ionization Detection of Non-Cholesterol Sterols as Indicators of Cholesterol Absorption and Synthesis in 158 Chinese Individuals with Normolipidemia, Hyperlipidemia, and Familial Hypercholesterolemia.

BACKGROUND There are limited studies on the effects of cholesterol homeostasis in populations at high risk for cardiovascular disease. We aimed to use gas chromatography and flame-ionization detection (GC-FID) of non-cholesterol sterols as indicators of cholesterol absorption and synthesis. Sterol indicators of cholesterol absorption included campesterol, stigmasterol, and sitosterol. Sterol indicators of cholesterol synthesis included squalene, 7-lathosterol, and desmosterol. MATERIAL AND METHODS A total of 158 participants were enrolled in 3 groups: healthy control (n=64), hyperlipidemia (n=69), and familial hypercholesterolemia (FH, n=25). Age, sex, blood pressure, blood glucose, and lipoprotein were collected, and cholesterol absorption and synthesis markers were determined by GC-FID. RESULTS All 6 cholesterol concentration indicators, except squalene, were significantly different among the 3 groups (all P<0.05); whereas in the ratio to cholesterol (%, sterols/cholesterol), only desmosterol and lathosterol were significantly different (P<0.05). Multifactorial regression analysis showed that triglycerides, total cholesterol, and desmosterol were independent risk factors affecting the development of hyperlipidemia (P<0.05). The efficacy of the ROC curve for the diagnosis of dyslipidemia was also higher for all 3 indices (Model 1, AUC=0.960). Model 1 was superior to Model 2 for the 6 indicators of cholesterol. For the FH and dyslipidemia groups, the 6-indicator model (Model 3) was shown to have a good diagnostic value (AUC=1.000). CONCLUSIONS The 6 sterol indicators of cholesterol absorption and synthesis had a dynamic course in all study participants. Desmosterol was an indicator of dyslipidemia. The combined use of the 6 sterol indicators differentiated between healthy individuals and patients with dyslipidemia and FH.

The importance of genetic counseling and genetic screening: a case report of a 16-year-old boy with resistant hypertension and severe hypokalemia.

Liddle's syndrome, an autosomal dominant form of monogenic hypertension, is characterized by salt-sensitive hypertension with early penetrance, hypokalemia, metabolic alkalosis, suppression of plasma rennin activity and aldosterone secretion, and a clear-cut response to epithelial sodium channel blockers but not spironolactone therapy. Here, we describe the case of a 16-year-old boy patient with resistant hypertension (maintain 170-180/100-110 mm Hg after administration four kinds of antiypertensive drugs) and severe hypokalemia. After a series of checks, we exclude primary aldosteronism and renal artery stenosis and other diseases. Finally, the Liddle syndrome was diagnosed because of the DNA sequencing found that the proband's mother and himself had mutations P616L (c.1847 C>T) in the SCNN1B gene. Liddle syndrome should be considered as a cause of hypertension in children or adolescents particularly with suppressed renin activity. Early diagnosis and appropriately tailored treatment avoid complications of long-term unrecognized or inappropriately managed hypertension. Genetic testing has made it possible to make accurate diagnoses and develop tailored therapies for mutation carriers. The role of genetic testing and genetic counseling in establishing the early diagnosis of Liddle's syndrome is important.

Expression of costimulatory molecule CD86 in HL-60 cells induced by MG132 and its effect on allogeneic mixed lymphocyte reaction / 中国实验血液学杂志

This study was aimed to elucidate the expression of costimulatory molecule CD80 and CD86 in HL-60 cells induced by proteasome inhibitor MG132 and its effect on allogeneic mixed lymphocyte reaction. Acute myelocytic leukemia cell line HL-60 and chronic myelocytic leukemia cell line K562 were cultured. The viability of the cells was measured by flow cytometry. Proteasome inhibitor MG132 at the concentrations of 2 or 3 µmol/L was used to stimulate the HL-60 cell cultured for 24 h and 48 h respectively, and the Annexin V/7-AAD staining and flow cytomotry were used to detect the apoptosis of the HL-60 cells. HL-60 and K562 cells were treated with 1 µmol/L MG132 for 24 h and 48 h respectively, then CD80 and CD86 antibodies were added, finally the expression of CD80 and CD86 was analysed by flow cytomery. The mRNA expression of CD86 in the HL-60 cells treated with 1 µmol/L MG132 was detected by RT-PCR. HL-60 and K562 cells were treated by 1 µmol/L MG132 and then underwent irradiation of 75 Gy (60)Co to kill the cells with their antigenicity preserved. Peripheral blood mononuclear cells (PBMNCs) of healthy volunteers, as reactive cells, were isolated and inoculated into the (60)Co irradiated HL-60 cells of different concentrations, as stimulating cells, CCK-8 was added and then the A value of absorbance was measured at the wave length of 450 nm in an enzyme labeling instrument. The results showed that the cell viability of the HL-60 cells treated with 1 µmol/L MG132 for 24 h an d 48 h was 92.95% and 85.87% respectively. The apoptotic rates of the HL-60 cells treated with MG132 increased in dose-and time-dependent manner. High-concentration of MG132 directly killed HL-60 cells. Before MG132 treatment K562 cells did not express CD86, but the CD86 expression of the HL-60 cells was up-regulated time-dependently after MG132 treatment (P < 0.01). The mRNA expression of CD86 in the HL-60 treated with MG132 was up-regulated time-dependently (P < 0.01). CCK-8 test showed that the proliferation level of PBMNC gradually increased along with the concentration of HL-60 cells treated with MG132 and reached its peak when the concentration of the HL-60 cells was 1×10(5) (P < 0.01). No remarkable proliferation of PBMNC was observed in the K562 groups no matter if the HL-60 cells had been treated with MG132. It is concluded that the high concentration of MG132 can directly kill HL-60 cells, low-concentration of MG132 can induce the expression of costimulatory molecule CD86 in HL-60 cells, also can improve the proliferation of PBMNC.

Urinary KIM-1, IL-18 and Cys-c as early predictive biomarkers in gadolinium-based contrast-induced nephropathy in the elderly patients.

BACKGROUND/AIMS: This study was designed to investigate whether urinary kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18) and cystatin C (Cys-C) are early predictive biomarkers for gadolinium-based contrast-induced nephropathy (Gd-CIN) in the elderly patients undergoing gadolinium-enhanced magnetic resonance imaging (MRI). METHODS: 60 elderly patients undergoing enhanced MRI using gadolinium-based contrast media were enrolled. Urine samples were collected before and 24 hours and 48 hours after the procedure, and KIM-1, IL-18 and Cys-C levels were measured by using an ELLSA kit respectively. Serum samples before and 24 hours and 48 hours after the procedure were also collected, and creatinine was measured by automatic biochemical analyzer. RESULTS: Gd-CIN was diagnosed in 8 of 60 (13.3%) patients. At 24 hours after MRI with gadolinium administration in the Gd-CIN group, the urinary KIM-1, IL-18 and Cys-C were significantly increased. Logistic regression analysis showed that urinary KIM-1 and IL-18 at 24 hours after gadolinium injection were independent predictive markers of Gd-CIN. The predictable time of acute kidney injury (AKI) onset determined by urinary KIM-1, IL-18 and Cys-C was 24 hours earlier than by serum creatinine. CONCLUSIONS: Urinary KIM-1, IL-18 and Cys-C could be early predictive biomarkers of Gd-CIN in the elderly patients, which showed a good performance in early diagnosis of Gd-CIN as compared with serum creatinine.

Mechanism of HL-60 cells apoptosis induced by proteasome inhibitor MG132 / 中国实验血液学杂志

The purpose of this study was to elucidate the apoptosis, apoptotic pathway of HL-60 cells induced by proteasome inhibitor MG132 and its effect on allogeneic mixed lymphocyte reaction. Apoptosis of HL-60 cells was detected by flow cytometry, the expression of P21, P27 and P53 proteins in HL-60 cells treated with MG132 was assayed by Western blot. The HL-60 cells were treated with 1 µmol/L MG132 for 48 h, and irradiated by 75 Gy of (60)Co γ-ray, but their antigenicity was preserved. The effect of irradiated HL-60 cells treated with MG132 on proliferation of peripheral blood mononuclear cells (PBMNC) was measured by CCK-8 method. The results showed that the apoptotic rate of MG132-treated HL-60 cells increased in dose-and time-dependent manner. No significant changes in MG132-induced apoptosis were observed after inhibiting caspase-8 and caspase-9 pathway. The expression of P21 and P27 protein increased after treatment of HL-60 cells with MG132. CCK-8 test showed that HL-60 cells induced with low-dose of MG132 displayed the enhancing effect on proliferation of PBMNC. It is concluded that high dose of MG132 can induce the apoptosis of HL-60 cells, and has direct killing effect on HL-60 cells, but this inducing apoptotic effect on HL-60 cells can not be realized through caspase-8 and caspase-9 pathway. The P21 and P27 protein may be involved in MG132 induced HL-60 cell apoptosis. Low dose of MG132 promotes the proliferation of PBMNC in healthy individuals and enhance the immunity of organism.

[Association of carotid atherosclerosis and blood pressure variation].

OBJECTIVE: To investigate the relationship of carotid artery plaque and blood pressure variation and cardiovascular risk factors. METHODS: We retrospectively analyzed clinical data of in-patients treated in the department of hypertension between April 2009 and June 2010. Information on carotid ultrasonography and other clinical date were obtained from 408 patients. All patients were monitored by ambulatory blood pressure. RESULTS: (1) Carotid artery determined in plaque was 55.3%, there was no differences between men and women. However, the carotid artery plague was associated positively with age. Increased age was associated with a significantly increased positive rate. (2) Cardiovascular risk factors and carotid artery plaque: carotid artery plaque was associated with duration of disease, fasting blood sugar, total cholesterol, and low density lipoprotein-cholesterol. (3) 24 h ambulatory blood pressure and carotid artery plaque: the prevalence of carotid artery plaque increased with increasing coefficient of systolic variation (P = 0.001). There was no correlation between the coefficient of diastolic variation and the prevalence (P = 0.644).(4) Multivariate regression analysis indicated that carotid artery plaque was associated with duration of hypertension, 24 h mean systolic blood pressure, and coefficient of variation of 24 h blood pressure (P < 0.05). CONCLUSION: Carotid atherosclerosis is independently associated with coefficient of variation of blood pressure, especially with coefficient of variation of systolic blood pressure.

[Incidence of impaired glucose tolerance in hospitalized essential hypertension patients without diabetes mellitus history and with normal fasting glucose].

OBJECTIVE: To observe the incidence of impaired glucose tolerance in hospitalized patients with essential hypertension without diabetes mellitus history and with normal fasting glucose. METHODS: A total of 586 hospitalized patients with essential hypertension and without known diabetes mellitus (DM) and with normal fasting blood glucose (FBG < 5.6 mmol/L) were included in this epidemiologic cross-sectional survey and screening study and received oral glucose tolerance test (OGTT). Associations between postprandial blood sugar and age, gender, body mass index, blood pressure level, blood lipid level, carotid arterial sclerosis were analyzed. RESULTS: (1) Among 586 patients, the number of impaired glucose tolerance (IGT) was 159, the number of newly diagnosed DM was 41 and the prevalence rates of newly diagnosed DM and impaired glucose tolerance (IGT) were 7.0% and 27.1% respectively. (2) Incidence of carotid arterial sclerosis was 67.5% in patients with impaired glucose tolerance and 59.6% in patients with normal glucose tolerance (P > 0.05). CONCLUSION: Our results showed that incidence of newly diagnosed disturbed glucometabolic status is common among patients with essential hypertension without DM history and normal FBG. OGTT should be used as a routine procedure in these patients for the purpose of early intervention in hypertensive patients with abnormal glucometabolic status.

[Efficacy, safety and tolerance of Felodipine controlled release tablets and Felodipine controlled release tablets associated combination therapy in the treatment of mild to moderate essential hypertension in China].

OBJECTIVE: To evaluate the efficacy, safety and tolerance of Felodipine controlled release tablets and Felodipine controlled release tablets associated combination each with Metoprolol, Lisinopril or Hydrochlorothiazide in the 12 weeks treatment of mild to moderate essential hypertension in China. METHODS: Multicenter, random samples, and open study have been processed. RESULTS: (1)After 12 weeks associated combination treatment of anti-hypertension, the percentages of the persons who had attained the target were 80.2% of ITT group in Felodipine controlled release tablets associated combination with Hydrochlorothiazide, 74.1% of ITT group in with Metoprolol,and 80.5% of ITT group in with Lisinopril, respectively. (2)Mean reductions of systolic/diastolic blood pressure from baseline were 16.8/10.6 mm Hg in combination with Hydrochlorothiazide, 16.6/10.7 mm Hg in combination with Metoprolol,and 18.0/12.8 mm Hg in combination with Lisinopril each. There was no significant difference among these three groups (P>0.05). With the Felodipine controlled release tablets treatment alone, the mean reductions from baseline was 24.8/17.5 mm Hg. But in combination with Lisinopril, the blood pressure could lower more quickly, and then could reach the target more rapidly. (3)In the ITT group, the drug compliance with Felodipine controlled release tablets was 97.7%, with those in combination with Hydrochlorothiazide 89.8%, with those in combination with Metoprolol 100.0%, and with those in combination with Lisinopril 96.4%. The main adverse event related to Felodipine was headache, and to Lisinopril was cough. CONCLUSION: Antihypertensive drug Felodipine controlled release tablets are good and effective. And Felodipine controlled release tablet associated combination each with Metoprolol, Lisinopril or Hydrochlorothiazide can make most patients reach the treatment target, with safety, good tolerance, and high compliance.