Multilayered insights: a machine learning approach for personalized prognostic assessment in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a complex malignancy, and precise prognosis assessment is vital for personalized treatment decisions. Objective: This study aimed to develop a multi-level prognostic risk model for HCC, offering individualized prognosis assessment and treatment guidance. Methods: By utilizing data from The Cancer Genome Atlas (TCGA) and the Surveillance, Epidemiology, and End Results (SEER) database, we performed differential gene expression analysis to identify genes associated with survival in HCC patients. The HCC Differential Gene Prognostic Model (HCC-DGPM) was developed through multivariate Cox regression. Clinical indicators were incorporated into the HCC-DGPM using Cox regression, leading to the creation of the HCC Multilevel Prognostic Model (HCC-MLPM). Immune function was evaluated using single-sample Gene Set Enrichment Analysis (ssGSEA), and immune cell infiltration was assessed. Patient responsiveness to immunotherapy was evaluated using the Immunophenoscore (IPS). Clinical drug responsiveness was investigated using drug-related information from the TCGA database. Cox regression, Kaplan-Meier analysis, and trend association tests were conducted. Results: Seven differentially expressed genes from the TCGA database were used to construct the HCC-DGPM. Additionally, four clinical indicators associated with survival were identified from the SEER database for model adjustment. The adjusted HCC-MLPM showed significantly improved discriminative capacity (AUC=0.819 vs. 0.724). External validation involving 153 HCC patients from the International Cancer Genome Consortium (ICGC) database verified the performance of the HCC-MLPM (AUC=0.776). Significantly, the HCC-MLPM exhibited predictive capacity for patient response to immunotherapy and clinical drug efficacy (P < 0.05). Conclusion: This study offers comprehensive insights into HCC prognosis and develops predictive models to enhance patient outcomes. The evaluation of immune function, immune cell infiltration, and clinical drug responsiveness enhances our comprehension and management of HCC.

Chronic pretreatment of metformin is associated with the reduction of the no-reflow phenomenon in patients with diabetes mellitus after primary angioplasty for acute myocardial infarction.

INTRODUCTION: Metformin is one of the most commonly prescribed antihyperglycemic agents for the treatment of type 2 diabetes. However, little is known about the effect of metformin on no-reflow in diabetic patients. AIM: In this study, we investigated retrospectively whether chronic pretreatment with metformin was associated with no-reflow in diabetic patients who underwent primary coronary intervention for acute myocardial infarction (AMI). RESULTS: A total of 154 consecutive diabetic patients who underwent primary angioplasty for a first ST-segment elevation myocardial infarction were studied. No-reflow was defined as a final TIMI flow of ≤2 or final TIMI flow of 3 with a myocardial blush grade of <2. The no-reflow phenomenon was found in 53 of 154 patients. There were no significant differences in clinical characteristics between the patients with and without metformin pretreatment. However, the 65 patients receiving chronic metformin treatment before admission had lower incidence of the no-reflow than those without it (4.2 and 14.6%, P < 0.05). Multivariable logistic regression analysis revealed that absence of metformin pretreatment was a significant predictor of the no-reflow along with high-burden thrombus, ejection fraction on admission and anterior AMI. CONCLUSION: These results suggested that chronic pretreatment with metformin may be associated with the reduction of the no-reflow phenomenon in patients with diabetes mellitus after primary angioplasty for AMI.

The effect of statins on the no-reflow phenomenon: an observational study in patients with hyperglycemia before primary angioplasty.

BACKGROUND: An association between admission plasma glucose levels and an increased risk of no-reflow has been well documented. Although HMG-CoA reductase inhibitor (statin) therapy can reduce no-reflow, little is known about its effect on no-reflow in patients with hyperglycemia. In the present study, we investigated whether pretreatment with a statin could reduce no-reflow in patients with hyperglycemia, who underwent primary coronary intervention for acute myocardial infarction (AMI). METHODS: A total of 259 consecutive patients who underwent primary angioplasty for a first AMI were studied. Blood glucose and creatinine kinase levels were measured on admission. All patients underwent 2-dimensional echocardiography and electrocardiographic analysis just after admission. No-reflow was defined as a Thrombolysis in Myocardial Infarction (TIMI) flow grade <3. Hyperglycemia was defined as a blood glucose level >or=10 mmol/L. Statin administration prior to admission was determined by detailed interview or information in the medical records. RESULTS: Hyperglycemia was diagnosed in 154 patients on admission. The no-reflow phenomenon was found in 31 of the 154 patients with hyperglycemia. The incidence of no-reflow was significantly greater in patients with hyperglycemia compared with no hyperglycemia. A multivariable logistic regression analysis showed that hyperglycemia on admission was an independent predictor of no-reflow. Among the 154 patients with hyperglycemia, there were no significant differences in baseline clinical characteristics between patients who received statin pretreatment and those who did not; however, hyperlipidemia occurred in a greater number of the patients who did not receive statin pretreatment. The 40 patients with hyperglycemia who received statins before admission had a lower incidence of no-reflow than those who did not receive statin pretreatment (5% and 25.4%; p < 0.05). Multivariable logistic regression analysis revealed that absence of statin pretreatment was a significant predictor of no-reflow in patients with hyperglycemia, along with ejection fraction on admission, initial TIMI 0 flow, number of Q waves, and anterior AMI. CONCLUSION: The results of our study show that pretreatment with statins could attenuate no-reflow after AMI in patients with acute hyperglycemia.

Remote periconditioning reduces myocardial no-reflow by the activation of K ATP channel via inhibition of Rho-kinase.

UNLABELLED: Remote periconditioning is induced by brief cycles of ischemia and reperfusion of a remote organ applied during sustained myocardial ischemia. It remains unknown whether the remote periconditioning reduces myocardial no-reflow. The adenosine triphosphate-sensitive potassium (K(ATP)) channel opening and inhibition of Rho-kinase may be the important mechanism of protection against myocardial no-reflow. Therefore, this study was sought to assess the effect of remote periconditioning on myocardial no-reflow and explore the possible mechanism. METHODS: Coronary ligation area and area of no-reflow were determined with pathological means in 58 mini-swines randomized into 7 study groups: 9 controls, 8 in remote periconditioning, 8 in hydroxyfasudil (a specific inhibitor of Rho-kinase)-treated, 9 in glibenclamide (K(ATP) channel blocker)-treated, 8 in remote periconditioning and glibenclamide, 8 in hydroxyfasudil and glibenclamide and 8 sham-operated. The ischemia and reperfusion model was created with 3 h of left anterior descending artery occlusion followed by 2 h of reperfusion. RESULTS: Compared with the control group, remote periconditioning decreased Rho-kinase activity (P<0.01), increased coronary blood volume (P<0.05), decreased area of no-reflow (from 82.3+/-3.9% to 45.5+/-5.7% of ligation area, P<0.01) and reduced necrosis size (from 98.5+/-1.3% to 74.7+/-6.3% of ligation area, P<0.05). Hydroxyfasudil had the same effect on the above parameters as remote periconditioning. Glibenclamide abrogated the effect of remote periconditioning or hydroxyfasudil on area of no-reflow and necrosis area, but not Rho-kinase activity. CONCLUSION: Remote periconditioning can reduce myocardial no-reflow after ischemia and reperfusion. This beneficial effect could be due to its activation of K(ATP) channel via inhibition of Rho-kinase.

Intravenous adenosine reduces myocardial no-reflow by decreasing endothelin-1 via activation of the ATP-sensitive K+ channel.

UNLABELLED: It has been verified that adenosine can attenuate myocardial no-reflow. However, the effects of adenosine on adenosine triphosphate-sensitive K+ (KATP) channel and endothelin-1 (ET-1) are unknown. METHODS: Forty mini-swines were randomized into 5 study groups: 8 in the control group, 8 in the adenosine pretreatment group, 8 in the glibenclamide (K(ATP) channel blocker)-treated group, 8 in the adenosine and glibenclamide-pretreated group and 8 in the sham-operated group. An acute myocardial infarction and reperfusion model was created with three-hour occlusion of the left anterior descending coronary artery followed by a one-hour reperfusion. RESULTS: Compared with the control group, adenosine significantly decreased the area of no-reflow (myocardial contrast echocardiography: from 78.5 +/- 4.5% to 20.7 +/- 4.1%, pathological means: from 82.3 +/- 1.9% to 21.5 +/- 4.3% of ligation area, respectively; all P < 0.01), reduced necrosis size from 98.5 +/- 1.3% to 75 +/- 4.7% of ligation area, P < 0.05). It also decreased plasma ET-1 and myocardial tissue ET-1. However, glibenclamide abrogated the protective effect of adenosine. CONCLUSION: The beneficial effect of adenosine on myocardial no-reflow could be due to its effect on ET-1 via the activation of K(ATP) channel.

Effect of statin therapy on reperfusion arrhythmia in patients who underwent successful primary angioplasty.

BACKGROUND: In animal models, pretreatment with statin can prevent reperfusion arrhythmia. In the observational study, we investigated whether pretreatment with statin may prevent reperfusion arrhythmia in patients who underwent primary coronary intervention for acute myocardial infarction (AMI). METHOD AND RESULTS: A total of 226 consecutive patients who underwent successful primary angioplasty for a first AMI were studied. Reperfusion arrhythmias were defined as all arrhythmias that occurred within 2 h after successful primary angioplasty. The reperfusion arrhythmia was found in 130 of 226 patients. There were no significant differences in clinical characteristics between the patients with and without statin pretreatment. However, the 41 patients receiving statin treatment before admission had lower incidence of the reperfusion arrhythmia than those without it (19.5% and 65.9%, P < 0.01). Multivariable logistic regression analysis revealed that absence of statin pre-treatment was a significant predictor of the reperfusion arrhythmia along with absence of pre-infarction angina and inferior AMI. CONCLUSION: Pre-treatment with statin could reduce the reperfusion arrhythmias after acute myocardial infarction in human.

Comparison of in-hospital and long-term outcomes between a Cypher stent and a Taxus stent in Chinese diabetic patients with coronary artery disease.

BACKGROUND: The sirolimus and paclitaxel distribution patterns and tissue residence time may be modified in atherosclerotic lesions for patients with diabetes, and the biological mechanisms of action for these agents differ significantly. Previous clinical trials have yielded discrepant results of major adverse cardiac events and restenosis between a sirolimus-eluting stent and a paclitaxel-eluting stent in coronary artery disease. Therefore, this study was conducted to compare in-hospital and long-term clinical outcomes between patients receiving sirolimus-eluting stent (Cypher or Cypher Select stent) and paclitaxel-eluting stent (Taxus Express stent) after percutaneous intervention (PCI) in Chinese patients with diabetes. METHODS: One hundred and sixty-four consecutive diabetic patients underwent PCI in Fuwai Hospital from April 2004 to December 2004. Of them, 101 patients received Cypher or Cypher Select stents (Cypher group, 145 stents) and 63 patients received Taxus Express stents (Taxus group, 129 stents). Repeat coronary angiography was performed at 6-month and clinical outcomes were evaluated at 1- and 3-year follow-up. Stent thrombosis was classified according to Academic Research Consortium (ARC). RESULTS: The two groups did not differ significantly with respect to cardiac death, recurrent myocardial infarction (re-MI), target vessel revascularization (TVR) and occurrence of major adverse cardiac events (MACE). And the MACE-free cumulative survival at 1- and 3-year follow-up and early, late and very late thrombosis rates were also similar in the two groups (all P > 0.05). There was a trend favoring PES over SES with regard to reducing cardiac death (0 vs 2.0%, P = 0.524), re-MI (0 vs 2.0%, P = 0.524), the composite of the cardiac death and re-MI (0 vs 4.0%, P = 0.299) and very late thrombosis (0 vs 3.0%, P = 0.295) between 1-year and 3-year follow-up. CONCLUSION: The study indicates that PCI with either Cypher or Taxus stents is associated with similar efficacy and safety in the small population of Chinese diabetic patients during long-term follow-up.

Is elevated high-density lipoprotein cholesterol always good for coronary heart disease?

BACKGROUND: High-density lipoprotein (HDL) could enhance inflammation in atherogenesis when inflammatory response is present, and the activity of paraoxonase and antioxidant in HDL in the elderly is significantly decreased. There might be a different role for high-density lipoprotein cholesterol (HDL-C) between different age groups in patients with coronary heart disease (CHD). METHODS: For this study, 225 inpatients with CHD (coronary atherosclerosis stenosis >/= 50% on >/= 1 major coronary arteries by coronary angiography), and 80 without CHD; 120 resting unstable angina patients, and 68 with stable angina were consecutively recruited. Risk factors were analyzed for CHD and resting unstable angina. RESULTS: High-density lipoprotein cholesterol in resting unstable angina was higher than that in stable angina (1.24 +/- 1.05 versus 1.05 +/- 0.29 mmol/L, p = 0.032). After adjustment for age, sex, physical inactivity, hypertension, diabetes, C-reactive protein, triglycerides, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) the adjusted odds ratio (OR) (95% CI) of resting unstable angina was 10.19 (2.18-47.6, p = 0.003) for HDL-C. Risk factors were further investigated in different age groups. Adjusted OR of CHD associated with HDL-C in < 55-year-old group was 0.09 (0.01-0.66, p = 0.018), in >/= 55-year-old group it was 0.55 (0.08-3.82, p > 0.05). Adjusted OR of resting unstable angina associated with high HDL-C was 19.24 (2.86-129.4, p = 0.002) in patients aged >/= 55 years. CONCLUSIONS: Elevated HDL-C might be an independent risk factor for resting unstable angina, even though HDL-C could play a much more important role in protection against coronary stenosis in younger or middle-aged persons.

Chronic pretreatment of ACEI reduces no-reflow in patients with acute myocardial infarction treated with primary angioplasty.

BACKGROUND: In animal models, pretreatment with angiotensin-converting enzyme inhibitor (ACEI) can reduce no-reflow. In the present study, we investigated whether pretreatment with ACEI may prevent no-reflow in patients who underwent primary coronary intervention for AMI. METHOD AND RESULTS: A total of 259 consecutive patients who underwent primary angioplasty for a first AMI were studied. No-reflow was defined as a TIMI flow grade < 3. The no-reflow phenomenon was found in 33 of 259 patients. There were no significant differences in clinical characteristics between the patients with and without ACEI pretreatment. However, the 47 patients receiving chronic ACEI treatment before admission had lower incidence of the no-reflow than those without it (4.2 and 14.6%, p<0.05). Multivariable logistic regression analysis revealed that absence of ACEI pretreatment was a significant predictor of the no-reflow along with absence of preinfarction angina, complete occlusion of the culprit lesion, high-burden thrombus, ejection fraction on admission, number of Q-waves, absence of statin pretreatment, and anterior AMI. CONCLUSION: Pretreatment with ACEI could preserve the microvascular integrity after acute myocardial infarction in humans.

Associations of apolipoprotein B with pulse pressure and glucose in Chinese families with familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL), with a marked elevation of apolipoprotein B (apoB), is estimated to cause 10-20% of premature coronary artery disease. However, little data are available to demonstrate the associations of apoB with pulse pressure and glucose levels in FCHL families in China. This study was to investigate the potential influence factors for blood pressure and glucose phenotypes in FCHL families by multiple linear regression analysis. We recruited 147 FCHL relatives and 90 spouses, aged 30 to 60 years, from 42 Chinese families with FCHL. Our results showed that triglyceride and low density lipoprotein cholesterol were associated with fasting glucose levels (all P<0.05). Body mass index and glucose significantly correlated to systolic blood pressure, diastolic blood pressure, and mean arterial pressure, respectively (all P<0.05). Furthermore, apoB was significantly related to pulse pressure and glucose in FCHL families (all P<0.05). Thus, this study demonstrates that apoB is significantly associated with pulse pressure and glucose levels in FCHL families. Accordingly, our data suggest that apoB may be a candidate risk marker for pulse pressure and glucose in FCHL populations.

Apolipoprotein B is associated with metabolic syndrome in Chinese families with familial combined hyperlipidemia, familial hypertriglyceridemia and familial hypercholesterolemia.

There is a paucity of data concerning the metabolic syndrome (MetS) in families with familial combined hyperlipidemia (FCHL), familial hypertriglyceridemia (FHTG), familial hypercholesterolemia (FH) and normolipidemic families in China. This study investigated the prevalence of MetS in these families and explored potential factors relevant to MetS. We recruited 70 families with 560 individuals > or = 20 years of age, including 43 FCHL families with 379 individuals, 3 FHTG families with 30 individuals, 16 FH families with 102 individuals and 8 normolipidemic families with 49 individuals. The definition of MetS is determined using modified criteria of National Cholesterol Education Program substituting body mass index for waist circumference. MetS is identified in 60.7% of FCHL patients and 71.4% of FHTG patients. The prevalence of MetS in family members is 36.7% for FCHL, 33.3% for FHTG, 17.6% for FH and 16.3% for normolipidemic families, with an odds ratio (OR) of 2.97 (95% CI 1.29-7.07, P=0.007) in FCHL families compared with normolipidemic families. Apolipoprotein B (apoB) is associated with MetS by multiple logistic analysis with an OR of 1.05 (1.03-1.07, P<0.001) in FCHL families, OR of 1.26 (1.03-1.55, P=0.026) in FHTG and OR of 1.07 (1.01-1.12, P=0.014) in FH families, independent of variables including age, gender, apolipoprotein A1, and low density lipoprotein cholesterol. Apolipoprotein A1 provided an OR of 0.95 (0.94-0.97, P<0.001) in FCHL families and OR of 0.94 (0.90-0.97, P=0.011) in FH families, but neither in FHTG nor in normolipidemic families (both P>0.05). Thus, apoB may be regarded as a relevant factor in the assessment of MetS in FCHL, FHTG and FH families. However, this finding needs to be verified by prospective studies in diverse ethnicities and warrants additional studies to elucidate possible mechanisms linking apoB to MetS.

Patients with low high-density lipoprotein-cholesterol or smoking are more likely to develop myocardial infarction among subjects with a visible lesion or stenosis in coronary artery.

BACKGROUND: Traditional contrast coronary arteriography affords only an indirect view of aspects of atheromata related to their propensity to trigger thromboses, so it is urgent to recognize the vulnerable person who is more likely to develop myocardial infarction (MI) among patients with visible lesion or stenosis in coronary artery. METHODS AND RESULTS: Two hundred and eighty-eight patients (144 MI patients, 144 controls) who had either a visible lesion or differing extent of stenosis in 1 or more major coronary arteries were consecutively enrolled. Lipid profile, C-reactive protein (CRP), smoking, hypertension, dyslipidemia and diabetes were analyzed for their association with MI. No differences in the prevalence of dyslipidemia, hypertension or diabetes was found between the patients with MI and those without, and CRP, triglycerides, total cholesterol and low-density lipoprotein-cholesterol levels did not differ between the 2 groups (all p>0.05). However, high-density lipoprotein-cholesterol (HDL-C) was significantly lower in the patients with MI than in those without (1.06+/-0.30 vs 1.14+/-0.32 mmol/L, p=0.024). On multivariate analysis after adjustment for age and gender, adjusted odds ratio (95% confidence interval) of MI was 0.44 (0.20-0.96) for HDL-C, p=0.038; 2.6 (1.48-4.56, p=0.001) for smoking, which indicated that high HDL-C was protective for MI, and smoking was associated with an increased risk of MI. CONCLUSIONS: The present findings indicate that among subjects with a visible lesion or stenosis in coronary arteries, those with low HDL-C or smokers are more likely to develop MI.

Apolipoprotein E polymorphism influences lipid phenotypes in Chinese families with familial combined hyperlipidemia.

BACKGROUND: Apolipoprotein E (apoE) polymorphism is associated with changes in the lipoprotein profile of individuals with familial combined hyperlipidemia (FCHL), but its effects on the lipoprotein profiles of members of Chinese families with FCHL remain uncertain. METHODS AND RESULTS: 43 FCHL families (n=449) and 9 normolipidemic families (n=73) were recruited to assess the influence of apoE polymorphism on plasma lipids. The relative frequency of the epsilon4 allele in affected and unaffected FCHL relatives, spouses and normolipidemic members was 13.8%, 5.3%, 9.1% and 6.8%, respectively, with a significantly higher frequency in affected FCHL relatives, compared with unaffected FCHL relatives or normolipidemic members (p=0.0002 or p=0.029). In FCHL relatives, the apoE4 subset (E4/4 and E4/3) exhibited significantly higher levels of apoB, total cholesterol and low-density lipoprotein-cholesterol (LDL-C) than did the apoE3 (E3/3) subset, especially in women (all p<0.05), and there was significant elevation of LDL-C concentrations in men only (p<0.05). In men, the apoE2 (E3/2) subset indicated a decreased level of apoB and increased apoA1 compared with those in the apoE3 subset (p<0.05). CONCLUSIONS: ApoE polymorphism appears to be associated with variance of the lipoprotein phenotype in Chinese families with FCHL.

Effect of age on progesterone receptor expression, and osteoprogenitor proliferation and differentiation in female rat vertebral cell populations.

In the present investigation, we evaluated whether the capacity for proliferation and differentiation of progesterone (Prog)-dependent osteoprogenitors in the female rat skeleton is related to the level of Prog receptors (PRs) and/or the level of circulating estrogen. We confirmed that in rats, estrogen levels at 18 months of age are higher than those at 3 months, and higher again in rats of 22.5, 25.5, and 26 months of age. Prog levels in rats of ages between 18 and 25.5 months were lower than those at 26 and 3 months of age. PR-A levels were tenfold higher than those of PR-B in cell populations where PR-B was detectable; PR-B receptors were not detectable in all cell populations. In populations derived from 22.5 to 26 months old rats, the basal levels of PR-A were higher than those derived from 3 and 18 months old rats by five- and twofold respectively. Prog treatment enhanced PR-A expression in animals of all ages. Estrogen enhanced the effect of Prog on PR-A expression in cell populations from the 3 and 18 months old rats, but had no effect on PR-A expression in cell populations from 22.5, 25.5, and 26 months old rats. This might be related to the high basal expression of PR in 22.5-26 months old rats (the 'persistent estrous' phase). Our results also confirm our previous observation that in rats, the number of Prog- and dexamethasone (Dex)- dependent osteoprogenitors, and the effect of estrogen on the response to Prog do not decrease with age. In conclusion, we have shown that the basal level of PR-A was increased in old rats, and that this correlated with increased serum estrogen levels, but not with the number of detectable Prog-dependent osteoprogenitors. We also found that Prog upregulates the expression of its own receptors and that estrogen enhances this in young rats but not in rats over 22.5 months of age, in which estrogen levels are elevated.

[Glycolytic and fatty acid metabolic enzyme changes early after acute myocardial ischemia].

OBJECTIVE: To explore the changes of mRNA and protein expressions of glycolytic and fatty acid metabolic enzymes early after acute myocardial ischemia. METHODS: Twelve dogs were randomly divided into 3 groups (sham, 20 min ischemia and 40 min ischemia, n = 4 each). Myocardial samples from ischemic and nonischemic zone were obtained for histology examination, and the mRNA expressions for Phosphofructokinase (PFK), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), GLUT1, GLUT4, Medium-chain acyl-CoA dehydrogenase (MCAD) and Heart-fatty acid binding protein (H-FABP) were determined by Real Time PCR-SYBR Green RT-PCR. GLUT1 protein expression was determined by immunohistochemistry. The apoptotic cardiomyocytes was evaluated by TUNEL. RESULTS: Compared to sham hearts, H-FABP mRNA was decreased in nonischemic and ischemic zone (P < 0.05) while GLUT1 mRNA expression was significantly increased in nonischemic and ischemic zone (P < 0.05) in dogs underwent 20 and 40 min ischemia. PFK mRNA tended to be higher in ischemic myocardium (P = 0.065) and GAPDH, MCAD as well as GLUT4 remained unchanged post ischemia (all P > 0.05). Positive GLUT1 protein staining was visualized in ischemic myocardium of hearts underwent 20 and 40 min ischemia. The myocardial apoptosis cells was 6.4% +/- 0.9% in sham hearts, 28.0% +/- 3.7% in hearts underwent 20 min ischemia (P < 0.05 vs. sham) and 38.4% +/- 1.9% in hearts underwent 40 min ischemia (P < 0.05 vs. sham). CONCLUSIONS: Significant down and up-regulated glycolytic and fatty acid metabolic enzymes early after myocardial ischemia suggested that these enzymes might play an important role in acute myocardial ischemia.

[Apolipoprotein B is associated with metabolic syndrome in Chinese pedigrees with familial hyperlipidemia].

OBJECTIVE: To investigate the prevalence of metabolic syndrome (MS) as well as the potential predictors in families with familial combined hyperlipidemia (FCHL), familial hypertriglyceridemia (FHTG), familial hypercholesterolemia (FH) and normolipidemic families in China. METHODS: The prevalence of MS was identified among 70 different families with 560 individuals aged > or = 20, including 43 FCHL families with 379 individuals, 3 FHTG families with 30 individuals, 16 FH families with 102 individuals and 8 normolipidemic families with 49 individuals. Diagnosis of MS was based on the modified criteria of National Cholesterol Education Program, US, substituting body mass index for waist circumference. Multivariate logistic regression was used to analyze the association between MS and different pedigrees. RESULTS: MS was identified in 60.7% of the FCHL patients and 71.4% of the FHTG patients. The prevalence of MS in the family members was 36.7% for the FCHL families, 33.3% for the FHTG families, 17.6% for the FH families, and 16.3% for the normolipidemic families, with an odds ratio (OR) of 2.97 (95% CI 1.29 to 7.07) in the FCHL families compared with in the normolipidemic families. Multivariate logistic regression showed an association between apolipoprotein (apo) B and MS with an OR of 1.05 (1.03 to 1.07) in the FCHL families, an OR of 1.26 (1.03 to 1.55) in the FHTG families, and an OR of 1.07 (1.01 to 1.12) in the FH families, independent of variables such as age, gender, apoA1, and LDL cholesterol, but showed no association in the normolipidemic families (P >0.05). Similarly, apo A1 provided an OR of 0.95 (0.94 to 0.97) in the FCHL families and an OR of 0.94 (0.90 to 0.99) in the FH families, but neither in the FHTG families nor in the normolipidemic families (both P >0.05). CONCLUSION: Apo B may be regarded as a relevant factor in the assessment of MS in FCHL, FHTG and FH families in Chinese. However, this finding needs to be verified by prospective studies in diverse ethnicities and warrants additional studies to elucidate the possible mechanisms linking apoB to MS.

Cytomegalovirus infection is associated with elevated interleukin-10 in coronary artery disease.

Previous studies show that cytomegalovirus (CMV) infection could increase the production of inflammatory cytokines in coronary artery disease (CAD). However, little is known about the influence of CMV infection on interleukin-10 (IL-10) levels in CAD. We attempted to investigate the relationships between CMV infection and serum IL-10 levels in patients with CAD. CMV IgG and serum levels of IL-10 were measured with ELISA in patients with CAD (n=463) and smooth coronary artery controls documented by coronary arteriography (n=125). Subjects were dichotomized according to calculated median level of IL-10 (6.84 pg/ml) in different groups or subgroups. The seropositivity of CMV IgG was more frequently found in the high IL-10 group than the low IL-10 group (46.8% versus 30.4%, P<0.001). The prevalence of CMV infection was significantly higher in the high IL-10 group than the low IL-10 group among the patients with CAD (48.1% versus 28.6%, P<0.001), but among the controls (40.4% versus 35.6%, P=0.588). On multiple logistic regression analysis, the adjusted odds ratio (95% confidence intervals) of high IL-10 associated with CMV infection was 2.3 (1.6-3.4, P<0.001) in the patients with CAD, and 1.1 (0.5-2.5, P=0.83) in the controls. We found a significant association of CMV infection with elevated IL-10 in the patients with CAD; therefore, we propose that changes in the immune response to CMV are a compounding factor in CAD.

Number, frequency, self-renewal, and expansion of osteoprogenitor cells (CFU-O) in subcultured female rat vertebral cell populations.

The present study was undertaken to determine whether the frequency and/or number of dexamethasone- and progesterone-responsive osteoprogenitors in cell populations derived from vertebrae of 6-week-old female rats could be increased relative to that of other progenitors. Frequencies and numbers of both progenitor types were determined for up to six subcultures using continuous subculturing, limiting dilution analysis, and colony assays. In dexamethasone-containing medium, subculturing resulted in an eightfold increase in the total number of dexamethasone-responsive osteoprogenitors and a 14-fold increase in progesterone-responsive osteoprogenitors in second subculture cells over first subculture cells without a significant increase in the frequency of these progenitors. From the third subculture onward, the frequency of both classes of osteoprogenitors decreased in a linear manner and none were observed after six subcultures. Similar results were obtained in progesterone-containing medium. Limiting dilution analysis in the presence of dexamethasone indicated that 2.61 % of cells represented a colony forming unit-fibroblast and 0.28 % represented an osteoprogenitor in first subculture cells, while in second subculture cells, these frequencies increased to 5.56 % and 0.40 %, respectively. Results show that while the frequency of colony forming unit-osteoprogenitor is not increased in the second subculture over the first, the total number of osteoprogenitors is greatly increased because of expansion of the total progenitor cell pool.

Herpes simplex virus type 2 infection is a risk factor for hypertension.

Herpes simplex virus type 2 (HSV-2), which has been recognized as a potential cardiovascular pathogen and implicated in carotid atherosclerosis and coronary artery disease, is independently associated with the future risk of cardiovascular death. Investigations have demonstrated that hypertension may be related to inflammation, and inflammation is one of the symptoms of HSV-2 infection. This cross-sectional study investigated the correlation between HSV-2 infection and essential hypertension. One thousand two hundred and forty four inpatients (488 patients with essential hypertension and 756 normotensives) were investigated serologically for the specific immunoglobulin G (IgG) to HSV-2 by enzyme-linked immunosorbent assay. Patients diagnosed with pheochromocytoma, primary aldosteronism, aorto-arteritis or renal artery stenosis were excluded. The prevalence of HSV-2 IgG seropositivity was significantly higher in the hypertensive group than in the normotensive group (38.3% vs. 29.8%, p =0.002). After adjustment for confounding factors, an association of HSV-2 IgG seropositivity with essential hypertension was found on binary logistic regression analysis. The adjusted odds ratio of essential hypertension was 1.4 (95% confidence intervals, 1.1 to 1.8; p =0.005) for HSV-2 infection; the adjusted covariates included age, male sex, smoking, body mass index, dyslipidemia, diabetes and coronary artery disease. The results of this study indicated that HSV-2 infection might be an independent risk factor for essential hypertension.