The Independent Association Between Age and Serum Cholesterol Levels in Patients with Familial Hypercholesterolemia.

BACKGROUND: Studies have suggested that age and the serum total cholesterol (TC) concentration are independent risk factors for cardiovascular disease (CVD) in patients with familial hypercholesterolemia (FH); however, the relationship between age and TC in patients with FH is unclear. We aimed to investigate the correlation between age and TC in patients with FH. METHODS: In this study, 103 patients with FH and 106 non-FH controls were recruited from 2004 to 2017. Spearman and partial correlation analyses, as well as multiple regression analyses, were used to evaluate the relationship between TC and age. RESULTS: There were no significant differences in age, gender, or BMI between the FH group and the control group (p > 0.05). Family history of CVD, TC, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), lipoprotein (a) (Lp[a]), and non-HDL-C levels were significantly higher in patients with FH compared with the controls (p < 0.01). Additionally, the serum TC levels for ages ≥ 50 years were significantly higher than those for ages < 50 years (p < 0.05) in FH patients. In both Spearman and partial correlation analyses, age was found to be significantly correlated with serum TC (p < 0.001) in the FH group but not in the control group, which was confirmed by further multiple linear regression analyses and logistic regression analyses. CONCLUSIONS: Age is an independent factor influencing serum TC level in patients with FH, and it is necessary to conduct early screening and early intervention.

Correlation of cardiovascular risk predictors with overweight and obesity in patients with familial hypercholesterolemia.

Purpose: We aimed to analyze the correlation between overweight and obesity-related indicators and cardiovascular risk predictors in patients with familial hypercholesterolemia (FH) and to evaluate their mutual predictive properties. Methods: A total of 103 patients with FH included from 2004 to 2017 were retrospectively analyzed. Pearson correlation analysis and multiple linear regression analysis were used to assess the correlation between overweight and obesity-related indicators and cardiovascular risk predictors in FH patients. Subject operating characteristic (ROC) curve was used to analyze their reciprocal predictive performance. Results: (1) Atherogenic index of plasma (AIP) (ß = 0.020) and ApoB/ApoA1 Ratio (BAR) (ß = 0.015) were independently correlated with body mass index (BMI) (P < 0.05); AIP (ß = 1.176) was independently correlated with waist-to-hip ratio (WHR) (P < 0.01); AIP (ß = 1.575), BAR (ß = 0.661) and atherogenic coefficient (AC) (ß = 0.427) were independently correlated with waist-to-height ratio (WHtR) (P < 0.05). (2) The area under the ROC (AUC) for overweight corresponding to AIP, BAR, and AC were 0.695 (95% CI = 0.593-0.797, P < 0.01), 0.660 (95% CI = 0.555-0.766, P < 0.01), and 0.632 (95% CI = 0.525-0.740, P < 0.05), respectively; and AUCs for central obesity corresponding to AIP, BAR and AC were 0.757 (95% CI = 0.656-0.857, P < 0.001), 0.654 (95% CI = 0.536-0.771, P < 0.05) and 0.651 (95% CI = 0.538-0.764, P < 0.05), respectively. The AUCs for moderate risk of AIP corresponding to BMI, WHR, and WHtR were 0.709 (95% CI = 0.608-0.811, P < 0.001), 0.773 (95% CI = 0.678-0.867, P < 0.001), 0.739 (95% CI = 0.641-0.836, P < 0.001), respectively, and BMI, WHR and WHtR corresponded to an AUC of 0.691 (95% CI = 0.585-0.797, P < 0.01), 0.734 (95% CI = 0.632-0.835, P < 0.001), and 0.706 (95% CI = 0.603-0.810, P < 0.01) for high risk of AIP, respectively. Conclusion: AIP has independent positive linear correlation with indicators related to overweight and obesity in FH patients; AIP has good predictive performance for overweight and obesity in FH patients, and WHR has good performance for identifying moderate and high risk of AIP in FH patients.

Involvement of the Hippo Pathway in the Development of Diabetes.

The Hippo pathway is a complex signaling network that plays an important role in regulating cellular and metabolic tissue processes, as well as in controlling organ size. However, various disorders and dysfunctions caused by disruptions in Hippo signaling harm parental pancreatic islet cells, promote apoptosis of parental cells, and impair insulin secretion -- leading to the occurrence of diabetes. Herein, we review the role of the Hippo pathway in islet offspring cells, as well as in the involvement of mammalian sterile 20 kinase-1 (MST1), large tumor suppressor-1/2 (LATS1/2), merlin, and yes-associated protein (YAP) in disruptions of Hippo signaling that lead to various disorders and the development of diabetes. Finally, we discuss several remaining issues in translating these promising discoveries into unique treatments in the future.

Agmatine and glycolipid metabolism. / 胍丁胺与糖脂代谢.

The prevalence of abnormal glucose and lipid metabolism and its relevant diseases has increased year by year, and it has become a problem that threatens human health. Therefore, finding a more effective way to prevent and treat diseases related to abnormal glucose and lipid metabolism has become an urgent public problem. Agmatine is a polyamine substance which widely presents in mammals.It is a metabolite produced by decarboxylation of L-arginine under the action of arginine decarboxylase, hence also known as decarboxylated arginine. Its biological effects have been confirmed. Previous studies have shown that agmatine possesses anti-diabetic effects in diabetic animals. Agmatine not only increases the insulin secretion form ß-pancreatic cells to inhibit the hyperglycemia, but also attenuates insulin resistance in rats. Agmatine also plays a positive role in lipid metabolism disorders and related diseases by modulating lipid metabolism and fatty acid oxidation.

Changes in Serum Lipid Profiles in Patients with Familial Hypercholesterolemia Who Smoke: A Pilot Study.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal codominant disease, and lipid abnormalities are a major risk factor for atherosclerotic cardiovascular disease (ASCVD). OBJECTIVES: We aimed to elucidate the lipid indicators that are significantly different between smokers and non-smokers and attempt to analyze their clinical implications in the risk of ASCVD in pedigrees of FH. METHODS: We screened 39 males aged 18-80 years with FH from the Chinese "National High Technology Research and Development Program" ("863 Project") after questionnaire survey, physical examination, and serum lipid test. RESULTS: The apoA1/apoB ratio and apoA1 were significantly correlated with the daily amount of cigarettes and smoking years, respectively (p<0.05). The serum apoB level was higher in smokers who smoke at least one stick per day than in non-smokers (p<0.05). Importantly, there was a significant difference in the apoA1/apoB ratio when the daily smoking amount exceeded one pack (p<0.05), and there was a significant difference in the apoA1 ratio when the smoking years exceeded 20 (p<0.05). CONCLUSION: The serum lipid profiles of apoA1 and apoB in smokers of FH pedigrees were significantly changed. With the increase of the smoking level, apoA1 decreased and apoB increased. Moreover, the ratio of apoA1 to apoB reflects the imbalance of cholesterol transport in blood vessels and might imply a higher risk of ASCVD in FH smokers.

Role of dyslipidemia in accelerating inflammation, autoimmunity, and atherosclerosis in systemic lupus erythematosus and other autoimmune diseases.

Dyslipidemia refers to the abnormality of lipid metabolism. The aberrant lipid profiles are usually characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-c), total cholesterol (TC), triglycerides (TGs), apoprotein B (ApoB), and decreased level of high-density lipoprotein cholesterol (HDL-c). Dyslipidemia occurs frequently in autoimmune diseases (ADs), such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type-1 diabetes mellitus (T1DM), psoriasis, and inflammatory bowel disease (IBD), and many other diseases. An imbalance in lipid metabolism contributes to accelerated inflammatory responses in addition to promoting the formation of atherosclerosis. Although there have been many studies and reports on the relationship between abnormal lipid metabolism and ADs, it remains uncertain as to whether dyslipidemia has a unique role in promoting the occurrence and development of ADs. Here, we discuss the mechanisms of how dyslipidemia accelerates inflammatory response, autoimmunity, and atherosclerosis at epidemiological, molecular, and cellular levels, and the discussion is mainly conducted with SLE as an example.

Cost-effectiveness analysis of routine 13-valent pneumococcal conjugate vaccinations in Chinese infants.

BACKGROUND: This study aimed to evaluate the cost-effectiveness of the 13-valent pneumococcal conjugate vaccine (PCV-13) compared to a no vaccination strategy in Chinese infants. METHODS: A Markov process model was developed to examine the outcomes of PCV-13 against a no vaccination strategy using data and assumptions adapted for relevance to China. Outcomes over a lifetime horizon are presented. One-way and probabilistic sensitivity analyses were performed to determine the uncertainty. RESULTS: Compared to no vaccination, a PCV-13 vaccination program would provide a gain of 0.009 additional quality-adjusted life years (QALYs) per subject. From the health care and societal perspectives, the incremental costs per QALY were $20,709 and 18,483, respectively. When herd effect was included, the cost effectiveness of the PCV-13 vaccination strategy was notably improved. The lower price of PCV-13 will improve the cost-effectiveness. CONCLUSIONS: The PCV-13 vaccination is likely to be cost-effective at the current Chinese prices and ceiling threshold ($8,382).

The role of aryl hydrocarbon receptor in bone remodeling.

Bone remodeling is a persistent process for maintaining skeletal system homeostasis, and it depends on the dynamic equilibrium between bone-forming osteoblasts and bone-resorbing osteoclasts. Aryl hydrocarbon receptor (Ahr), a ligand-activated transcription factor, plays a pivotal role in regulating skeletal system. In order to better understand the role of Ahr in bone remodeling, we focused on bone remodeling characteristic, and the effects of Ahr on bone formation and differentiation, which suggest that Ahr is a critical control factor in the process of bone remodeling. Moreover, we discussed the impacts of Ahr on several signaling pathways related to bone remodeling, hoping to provide a theoretical basis to improve bone remodeling.

Cost-effectiveness of a 23-valent pneumococcal polysaccharide vaccine immunization programme for the elderly in Shanghai, China.

BACKGROUND: To evaluate the cost-effectiveness of adding 23-valent pneumococcal polysaccharide vaccine (PPSV23) to the immunization schedule for the elderly population (age>60years) in Shanghai, China. METHODS: A decision-tree model, with data and assumptions adapted from the societal perspective of Shanghai City, was developed to project the health outcomes of PPSV23 vaccination (compared with no vaccination) over a lifetime course. Sensitivity analysis was used to test the model's robustness. The clinical data, utility and treatment costs related to pneumococcal diseases were either cited from the literature or calculated from local sources. RESULTS: The incremental cost-effectiveness ratio of PPSV23 vaccination compared with no vaccination was $16,699/quality-adjusted life years gained, which was lower than the per capita GDP of Shanghai ($16,840). Sensitivity analyses showed that the model's outcome is robust. CONCLUSIONS: Routine vaccination of the elderly population with PPSV23 is cost-effective in Shanghai, China.

Modeling the impact of the 7-valent pneumococcal conjugate vaccine in Chinese infants: an economic analysis of a compulsory vaccination.

BACKGROUND: The purpose of this study was to compare, from a Chinese societal perspective, the projected health benefits, costs, and cost-effectiveness of adding pneumococcal conjugate heptavalent vaccine (PCV-7) to the routine compulsory child immunization schedule. METHODS: A decision-tree model, with data and assumptions adapted for relevance to China, was developed to project the health outcomes of PCV-7 vaccination (compared with no vaccination) over a 5-year period as well as a lifetime. The vaccinated birth cohort included 16,000,000 children in China. A 2 + 1 dose schedule at US$136.51 per vaccine dose was used in the base-case analysis. One-way sensitivity analysis was used to test the robustness of the model. The impact of a net indirect effect (herd immunity) was evaluated. Outcomes are presented in terms of the saved disease burden, costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio. RESULTS: In a Chinese birth cohort, a PCV-7 vaccination program would reduce the number of pneumococcus-related infections by at least 32% and would prevent 2,682 deaths in the first 5 years of life, saving $1,190 million in total costs and gaining an additional 9,895 QALYs (discounted by 3%). The incremental cost per QALY was estimated to be $530,354. When herd immunity was taken into account, the cost per QALY was estimated to be $95,319. The robustness of the model was influenced mainly by the PCV-7 cost per dose, effectiveness herd immunity and incidence of pneumococcal diseases. With and without herd immunity, the break-even costs in China were $29.05 and $25.87, respectively. CONCLUSIONS: Compulsory routine infant vaccination with PCV-7 is projected to substantially reduce pneumococcal disease morbidity, mortality, and related costs in China. However, a universal vaccination program with PCV-7 is not cost-effective at the willingness-to-pay threshold that is currently recommended for China by the World Health Organization.

Effects of Kir2.1 gene transfection in cochlear hair cells and application of neurotrophic factors on survival and neurite growth of co-cultured cochlear spiral ganglion neurons.

Immature inner hair cells (IHCs) produce spontaneous action potentials, which may be associated with the survival of spiral ganglion neurons (SGNs) during early development. Later, this activity ceases in part by the expression of Kir channels. In the present study, SGNs were co-cultured with organ of Corti in which a Kir2.1 channel was over-expressed in an attempt to block the spontaneous activity of IHCs. The over-expression led to a reduced survival and neurite growth accompanied by increased SGN apoptosis. The enhanced activation of apoptosis was consistent with the inhibition of the survival-promoting pathway and the disruption of [Ca(2+)](i) homeostasis. Furthermore, the effect of Kir2.1 over-expression can be reversed by exogenous neurotrophic factors (NTFs). These results are consistent with the hypothesis that the earlier-than-normal expression of Kir2.1 in HCs inhibits their spontaneous activity required for SGN survival and neurite growth.

[Association of endothelial nitric oxide synthase gene polymorphism with level of uric acid in serum for acute coronary syndrome].

OBJECTIVE: To evaluate the association of elevation in serum uric acid with the development of coronary artery disease, and to determine the relationship between uric acid and Glu(298) Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene in acute coronary syndrome (ACS) in the Chinese Han Nationality. METHODS: The Glu(298) Asp variant of the eNOS gene was detected by polymerase chain reaction/restriction fragment length polymorphism analysis in 58 patients with ACS and 43 healthy controls. The severity of ACS was expressed by the number of affected vessels and by the Duke scoring system. RESULTS: The frequencies of the eNOS Glu/Glu, Glu/Asp, and Asp/Asp genotypes in the ACS group were not significantly different from those of controls (43.1%, 36.2%, 20.7% vs. 48.8%, 34.9%, 16.3%, respectively; chi (2) = 0.446, P = 0.800). In comparison with subjects who had Glu(298) allele in the eNOS gene, the risk of ACS was not increased among Asp/Asp carriers (odds ratio 1.34, 95% confidence interval 0.479 to 3.755, P = 0.575). There was no significant association between the eNOS Glu(298) Asp variant and the Duke score [(46.73+/-19.90) score for Asp/Asp vs. (48.33+/-19.61) score and (38.19+/-15.12) score for Glu/Glu and Glu/Asp, respectively, P=0.248], but there was a significant association between the eNOS Glu(298) Asp variant and the serum uric acid level in ACS group [(298.92+/-87.27) micromol/L for Glu/Glu vs.(380.80+/-95.80) micromol/L and (346.16+/-93.71) micromol/L for Glu/Asp and Asp/Asp, respectively, P = 0.017]. CONCLUSION: Glu(298) Asp polymorphism of the eNOS gene appears to have no association with ACS in the Chinese Han Nationality, but a significant association between the eNOS Glu(298) Asp variant and the serum uric acid level is found in patients with ACS.

WITHDRAWN: Expression of p53, p63, and p73 isoforms in squamous cell carcinoma and adenocarcinoma of esophagus☆,☆☆

This article has been withdrawn consistent with Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher apologizes for any inconvenience this may cause.

[The effect of atorvastatin on the expression of CD55, CD59 in patients with hyperlipidemia].

OBJECTIVE: To study the expressions of CD55 and CD59 in patients with hyperlipidemia and the effects of atorvastatin on it, and to identify the possible influential factors. METHODS: We selected 67 patients with hyperlipidemia, and 24 healthy people matched in terms of age, sex and body weight as control. The expressions of CD55 and CD59 on white blood cells were detected by flow cytometry, and their relationships to blood lipids, complement activation indexes (C(5a), sC(5b-9)), inflammatory factors (high sensitivity C-reactive protein (hsCRP), TNF-alpha, IL-6 were analyzed. 24 patients with hyperlipidemia were treated with atorvastatin for 8-12 weeks and the expressions of CD55 and CD59 were measured before and after atorvastatin therapy. RESULTS: The mean fluorescence intensity (MFI) of CD55 lymphocytes and monocytes were decreased in patients with hyperlipidemia compared with control (2.07 +/- 0.28 vs 2.29 +/- 0.44 and 3.45 +/- 1.02 vs 4.33 +/- 2.32, P < 0.01 and P < 0.05, respectively). CD55 positive lymphocyte MFI was negatively correlated with waist circumference, waist-hip ratio, hsCRP and C(5a). C(5a) was negatively correlated with the MFIs of CD55 positive lymphocytes, monocytes, granulocytes, and positively with TG and diastolic blood pressure. After atorvastatin therapy, the MFIs of CD59 positive lymphocytes, monocytes and granulocytes increased (4.34 +/- 1.16 vs 3.69 +/- 0.76, 4.52 +/- 1.36 vs 3.91 +/- 0.89, 5.67 +/- 1.72 vs 4.56 +/- 1.03, P < 0.05, < 0.05 and < 0.01 respectively), which were not correlated with changes of blood lipids. CONCLUSIONS: The expression of CD55 is down-regulated in hyperlipidemia, which might be influenced by obesity, abdominal distribution of adipose tissue and inflammatory status of hyperlipidemia, but not by blood lipids. The expression of CD55 is related with complement activation; The expression of CD59 is up-regulated after atorvastatin treatment independently of blood lipids.

Suppressive effect of Astragalus membranaceus Bunge on chemical hepatocarcinogenesis in rats.

Astragalus membranaceus (AM) has been widely used for treating liver diseases in traditional Chinese medicine. Experimental evidence indicates that it has antitumor potential. In this study, the effect of AM on hepatocarcinogenesis induced by diethylnitrosamine (DEN), two-thirds partial hepatectomy, and 2-acetylaminofluorene (2-AAF) (DEN-PH-AAF) was evaluated using glutathione S-transferase placenta form (GST-P) as marker. First, rats were injected intraperitoneally (i.p.) with DEN (200 mg/kg in saline), a two-thirds partial hepatectomy was carried out 2 weeks later, and the rats were then placed on a basal diet containing 0.02% AAF from week 3 to week 8 to induce hepatocarcinogenesis. The rats were given AM (90 mg/kg or 180 mg/kg body weight) by gavage from week 3 to week 8 (treatment groups). The formation of GST-P-positive foci and the expression of GST-P protein and mRNA caused by DEN-PH-AAF were reduced in the treatment groups, which clearly suggests that AM is effective in delaying DEN-PH-AAF-induced hepatocarcinogenesis.