Objectives:Fenofibric acid is extracted from the widely used hypolipemic fenofibrate,nowadays being approved for marketing around numerous nations and regions,nonetheless not in China.Present trial evaluated the efficacy and safety in the Chinese hypertriglyceridemia population. Methods:This is a multi-center,randomized,double-blind,placebo-controlled phase Ⅲ clinical trial.Patients from 3 different cohorts,including severe hypertriglyceridemia(HTG),moderate HTG and mixed-dyslipidemia(MD),were randomized at 1:1 ratio to receive fenofibric acid 135 mg or placebo daily for 12 weeks.The primary endpoint was the percentage change of triglyceridemia(TG)from baseline at week 12.Secondary endpoints were the percentage changes of other blood lipid indexes.At the same time,the incidence of medical adverse events was observed. Results:Among the three cohorts of patients with severe HTG(n=52),moderate HTG(n=23)and MD(n=52),the TG levels in the fenofibric acid-treated group decreased by(49.12±29.19)%,(49.95±25.19)%and(49.79±19.28)%,respectively from baseline to 12 weeks,while the corresponding placebo groups decreased by(18.88±40.69)%,(8.11±29.86)%and increased by(10.42±73.04)%,respectively from baseline to 12 weeks.The differences between treatment and placebo groups were statistically significant(P<0.017 for severe HTG cohort,P<0.05 for moderate and MD cohort).The high-density lipoprotein cholesterol(HDL-C)in the fenofibric acid-treated group increased by(25.51±21.45)%,(24.55±24.73)%,and(23.60±27.38)%,and the placebo group increased by(1.91±20.42)%,(2.40±9.32)%and(7.13±19.12)%,respectively,the differences between the two groups were statistically significant(all P<0.05).In the fenofibric acid group,adverse events with incidence>5%included upper respiratory tract infection(10.9%),abdominal pain(6.3%),and increased serum creatinine levels(6.3%),rates of adverse events were similar between the two groups(P>0.05). Conclusions:Fenofibric acid can significantly reduce triglycerides and elevate HDL-C levels safely in Chinese patients with severe to moderate HTG without statin or MD patients on top of statin therapy.

Apolipoprotein A5 (Apo A5) is a novel member in apolipoprotein family, which is proven to be an important regulator in triglyceride metabolism, especially in adjusting the TG content in plasma. Apo A5 gene polymorphisms affect triglyceride metabolism and atherosclerotic cardiovascular diseases. The research focuses on -1131T>C, c.56C>G, and c.553G>T.
Apolipoprotein A-V ; genetics ; Atherosclerosis ; genetics ; Gene Frequency ; Humans ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Triglycerides ; metabolism

Liver fibrosis has a complex pathogenesis and involves various intracellular and extracellular signal transduction pathways, but its specific pathogenesis remains unclear. Recent studies have confirmed that the activation of hepatic stellate cells due to abnormal activation of the Wnt signaling pathway is an important cause of liver fibrosis, and targeted inhibition of the Wnt signaling pathway can prevent the activation and proliferation of hepatic stellate cells and thus achieve an antifibrogenic effect. This article reviews the role of the Wnt signaling pathway in the development and progression of liver fibrosis and the latest research advances in the antifibrogenic effect of the interference of the Wnt signaling pathway, in order to provide new ideas for anti-hepatic fibrosis and the delay of early-stage cirrhosis.

Objective To explore the association between X-ray repair cross complementing group 1 (XRCC1)gene rs25487 locus polymorphisms and nonobstructive azoospermia in Hui minority ethic population of Shaanxi Province.Methods We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)method for genotyping at XRCC1 gene rs25487 locus in 79 patients with nonobstructive azoospermia and 82 healthy male controls in Hui minority ethic population of Shaanxi Province.Then we analyzed the association be-tween XRCC1 gene rs25487 locus and nonobstructive azoospermia.Results Compared with GG genotype,GA, AA and GA + AA genotypes demonstrated a significantly increased risk for nonobstructive azoospermia (OR =2.286,95% CI 1.1 5 1-4.539;OR =2.202,95% CI 0.753-6.439;OR =2.271,95% CI 1.1 71-4.403),respec-tively.Meanwhile,the A allele frequency was significantly higher in azoospermic patients than in controls (OR =1.582,95% CI 1.005-2.492,P =0.047).Conclusion G→A in XRCC1 gene rs25487 locus is correlated with nonobstructive azoospermia in Hui minority ethic population of Shaanxi province.

Objective To examine the influence of LEV adjunctive treatment on cognitive function and life quality in RE school-age children. Methods Fifty-five cases of RE children were selected from our hospital from June 2013 to December 2015. Based on original treatment all children were added with LEV treatment for 16 weeks. The initial dose was 8~10 mg/(kg·d),and gradually increased to 50 mg/(kg·d). maintenance dose was 30 mg/(kg·d). Adverse drug reac?tions were recorded and clinical efficacies were determined after treatment. Wechsler Intelligence Scale for Children re?vised in China (WISC-CR) and quality of life in children with epilepsy (QOLCE) was used to evaluate children's cogni?tive function and children's life quality, respectvely. Results Average epilepsy attack frequencies after treatment (3.8± 1.3 vs. 6.6±2.3) times/month decreased significantly compared with before treatment (P<0.05). Clinical control ratio, ex?cellent ratio, effective ratio and ineffective ratio after treatment were 9.1%, 36.4%, 43.6%, 36.4%respectively and total effective ratio was 89.1%. The arithmetic score (10.9 ± 2.6 vs. 9.2 ± 2.1) and mapping score (15.1 ± 3.9 vs. 13.8 ± 3.3) in WISC- CR evaluation increased significantly (P<0.05). Life quality score (65.7 ± 5.7 vs. 62.8 ± 4.9) , cognitive function score (60.0 ± 5.7 vs. 57.4 ± 6.2) and social function score (65.0 ± 6.3 vs. 62.5 ± 5.5) after treatment in QOLCE evaluation in?creased significantly (P<0.05). During medication, the incidences of dizziness, fatigue, lethargy, irritability, euphoria and transient aminotransferase elevation were 12.7%, 9.1%, 20.0%, 9.1%, 3.6%and 3.6%respectively. Sixteen week medica?tion retention rate was 96.4%. Conclusion LEV adjunctive treatment can significantly reduce epilepsy attacks and im?prove cognitive function and life quality in RE children, but attention should be paid to LEV's influence on mental behavior.

Objective To analyze the current status of cholesterol goal attainment for the primary and secondary prevention of cardiovascular disease in dyslipidemia patients using data from the DYSIS-China study.Methods Based on criteria defined in the 2014 China Cholesterol Education Program (CCEP) and the 2007 Chinese guidelines for the prevention and treatment of dyslipidemia in adults,25 317 dyslipidemia patients enrolled in the DYSIS-China study (from March 2012 to October 2012) were stratified to the atherosclerotic cardiovascular disease (ASCVD) primary prevention and secondary prevention groups.The total cholesterol (TC) target goals were ＜3.11,4.14,5.18,and 6.22 mmol/L,respectively,and the lowdensity lipoprotein cholesterol (LDL-C) therapeutic goals were less than 1.8,2.6,3.4,and 4.1 mmol/L,respectively,for the very high-risk,high-risk,moderate-risk,and low-risk patients in the primary prevention group.The TC targets for the very high-risk and high-risk patients were ＜ 3.11 and ＜ 4.14 mmol/L,respectively,and the LDL-C targets were ＜ 1.8 and ＜ 2.6 mmol/L,respectively,in the secondary prevention group.The TC and LDL-C goal attainment rates were calculated for the different risk groups according to the targets values.Results Totally,71.09％ (n =18 000) of the dyslipidemia patients were grouped into very high and high risk groups,51.76％ (n =13 104) and 48.24％ (n =12 213)patients were stratified to primary and secondary prevention of ASCVD.The LDL-C and TC goal attainment rates for the secondary prevention group were 33.09％ (4 041 cases) and 21.05％ (2 571 cases),respectively.The LDL-C and TC goal attainment rates for the primary prevention group were 52.40％ (6 866 cases) and 42.06％ (5 511 cases),respectively.Multivariate logistic regression analysis showed that diabetes mellitus (OR =5.75,4.15,P ＜ 0.05),coronary heart disease (OR =5.70,3.58,P ＜ 0.001),and peripheral arterial disease(OR =2.42,1.49,P ＜ 0.05) were risk factors for failure to achieve TC and LDLC goals,respectively.Conclusions Despite the widespread application of the 2014 CCEP and 2007 Chinese dyslipidemia guidelines,LDL-C goal attainment among secondary and primary prevention patients remains suboptimal in China.More rigorous guideline adherence is therefore required to increase the LDL-C and TC goal attainment rates and improve the long-term cardiovascular outcomes in Chinese dyslipidemia patients.

Objective To assess the efficacy and safety of fluvastatin sodium extended-release tablets (fluvastatin XL) 80 mg once daily compared to fluvastatin sodium immediate-release capsules (fluvastatin IR) 40 mg twice daily in Chinese hyperlipidemic patients with moderate or high cardiovascular risk.Methods In this multi-center,randomized,double-blind,double-dummy,active-controlled,parallel-group study,after 6-week open-label treatment with fluvastatin IR 40 mg once daily,patients who did not reach their lipid goals were randomized to 12-week double-blind treatment with fluvastatin XL 80 mg once daily or fluvastatin IR 40 mg twice daily.Results (1) There were 218 patients enrolled in each group.At the study endpoint,no statistical difference was found in the mean percent change from baseline for LDL-C with-8.69％ [from (3.504 ±0.060) mmol/L to (3.153 ±0.065) mmol/L] in the fluvastatin XL group and-7.89％ [from (3.491 ±0.050) mmol/L to (3.181 ±0.060) mmol/L] in the fluvastatin IR group (P ＞ 0.05).The 95％ CI for difference between the two groups in adjusted mean percent change from baseline was (-4.70％-3.09％),which was within the pre-specified non-inferiority margin.In the fluvastatin XL group,the proportion of patients with moderate cardiovascular(CV) risk and high CV risk achieving their LDL-C treatment goals at endpoint was 50.0％ and 31.5％ respectively,while the proportion was 42.5％ and 24.5％ respectively in the fluvastatin IR group.No significant difference was found between the two groups in the proportion of patients who reached their lipid goals and the changes from baseline with other lipid parameters.(2)Similar safety profiles were observed in the two treatment groups,with 21.1％ adverse event (AE) (8.3％ study-drug related AE) in the fluvastatin XL group and 17.0％ AE (6.3％ study-drug related AE) in the fluvastatin IR group.Conclusion The efficacy of fluvastatin XL 80 mg once daily is comparable to fluvastatin IR 40 mg twice daily in Chinese hyperlipidemic patients with moderate or high cardiovascular risk and both treatments are safe and well-tolerated.

BACKGROUNDHypoxic pulmonary hypertension (HPH) contributes to the pathogenesis of cardiopulmonary diseases. Several lines of evidence indicate that the Rho A/Rho-kinase pathway play an important role in the progress of pulmonary hypertension. Stains have been shown exert numerous biological effects that are independent of their cholesterol-lowering property. We hypothesized that the Rho A/Rho-kinase pathway is involved in the pathogenesis of HPH, and that atorvastatin would attenuate involvement of the Rho A/Rho-kinase pathway in a HPH rat model.

METHODSThirty-two Wistar rats were randomly divided into four groups: control group, hypoxic group, atovastatin group, and normal saline group. The control group was kept in a normoxia environment. The other groups were exposed to hypoxia for three weeks. Atovastatin was administered daily via a gastric gavage in the atovastatin group. We measured the mean pulmonary arterial pressure (mPAP), the ratio of the right ventricular weight to the sum of the weights of the left heart ventricle and septum (RV/(LV+S)), arteriole wall thickness/vascular external diameter (WT%), vascular area/total vascular area (WA%), expression of RhoA and phos-MYPT-1 protein in lung tissue, and NF-κB activation in pulmonary vascular smooth muscle cells.

RESULTSCompared with the control group, mPAP, RV/(LV+S), WT%, WA%, NF-κB activation, expression of RhoA, and phos-MYPT-1 were increased in the hypoxic and normal saline groups (P < 0.05). Compared with the hypoxic group, mPAP, RV/(LV+S), WT%, WA%, NF-κB activation, expression of RhoA, and phos-MYPT-1 were decreased in the atovastatin group (P < 0.05). Correlations between phos-MPTY-1 and mPAP, WA%, WT%, and NF-κB activation were all positive.

CONCLUSIONSThe Rho A/Rho-kinase pathway plays an important role in the development of HPH. Atorvastatin reversed HPH by inhibiting the activity of Rho A/Rho-kinase and NF-κB.

Animals ; Atorvastatin Calcium ; Blotting, Western ; Heptanoic Acids ; therapeutic use ; Hypertension, Pulmonary ; drug therapy ; enzymology ; Hypoxia ; metabolism ; Male ; NF-kappa B ; metabolism ; Pyrroles ; therapeutic use ; Random Allocation ; Rats ; Rats, Wistar ; Signal Transduction ; drug effects ; rho-Associated Kinases ; metabolism ; rhoA GTP-Binding Protein ; metabolism

Atherosclerosis ; prevention & control ; Cholesterol, LDL ; blood ; Humans ; Hypercholesterolemia ; drug therapy ; United States

OBJECTIVE: To evaluate the effect of Ac-hE-18A-NH2 on TNF-α secretion and mRNA expression in ox-LDL-stimulated RAW264.7 macrophages and to elucidate the possible mechanisms. METHODS: Macrophages were incubated in the medium containing various concentrations of Ac-hE18A-NH2 (1-50 μg/mL) with ox-LDL (50 μg/mL) stimulated. The TNF-α level and intracellular cholesterol content were measured by commercially available quantitation kits following the manufacturer's instructions. TNF-α and ATP-binding cassette transporter A1 (ABCA1) mRNA expression were detected by real-time PCR. ABCA1 and IκB protein -expression in the macrophages were determined by Western blot. NF-κB activity was evaluated by electrophoretic mobility shift assay (EMSA). RESULTS: Ox-LDL stimulation induced a significant increase in TNF-α secretion, mRNA expression, cholesterol accumulation and nuclear factor-κB (NF-κB) activity in RAW264.7 macrophages. Ac-hE-18A-NH2 reduced TNF-α secretion and mRNA expression, up-regulated the ABCA1 mRNA and protein expression, reduced the intracellular cholesterol content, and inhibited NF- κB activation in a dose-dependent manner. Under the same condition and the same concentration, Ac-hE-18A-NH2 was more efficient than D-4F (apoA-I mimetic peptide) in inhibiting the inflammatory response induced by ox-LDL in the macrophages. CONCLUSION Ac-hE-18A-NH2 may suppress TNF-α secretion and mRNA expression in ox-LDL stimulated RAW264.7 macrophages via IκB-NF-κB signaling pathway. The anti-inflammatory effect of Ac-hE-18A-NH2 is better than that of apoA-I mimic peptide D-4F.
ATP Binding Cassette Transporter 1 ; metabolism ; Animals ; Cell Line ; Cholesterol ; metabolism ; Gene Expression Regulation ; I-kappa B Proteins ; metabolism ; Inflammation ; metabolism ; Lipoproteins ; pharmacology ; Lipoproteins, LDL ; Macrophages ; metabolism ; Mice ; NF-kappa B ; metabolism ; Peptide Fragments ; pharmacology ; Signal Transduction ; Tumor Necrosis Factor-alpha ; metabolism