AIMTo study the regulation mechanism of GP on plasma lipoprotein metabolism and To explore its mechanism of anti-lipoperoxidation in the experimental hyperglycemia rats.

METHODSThe rats were raised with high fat diet for six weeks,and the model of hyperglycemia was then established. After that, those rats were treated with high or low dose of GP and xuezhikang as a masculine comparison for four weeks. Then, those rat were executed, and detected the plasma TC, TG, LDL-C, HDL-C, GSH-Px, at the same time the SOD, CAT and MDA concentration also be mensurated.

RESULTSThe results showed that high and low dose of GP could decrease the concentration of serum LDL-C, cholesterol and triglyceride remarkably and raise the concentration of HDL-C. The activity of GSH-Px, SOD and CAT in GP groups were promoted and the level of MDA was decreased distinctly.

CONCLUSIONThe GP can therapy the abnormity of serum lipid and has obviously anti-lipoperoxidation affection.

Animals ; Cholesterol ; blood ; Cholesterol, LDL ; blood ; Gynostemma ; Hyperlipidemias ; drug therapy ; metabolism ; Lipid Peroxidation ; Lipids ; blood ; Lipoproteins, HDL ; blood ; Male ; Phytotherapy ; Plant Extracts ; therapeutic use ; Rats ; Rats, Wistar ; Triglycerides ; blood

BACKGROUNDAmerican College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) guidelines gave fondaparinux a class I recommendation for use in patients with non-ST elevation acute coronary syndromes (NSTE-ACS) undergoing invasive or conservative strategy. Nadroparin is one of the common anticoagulants used in NSTE-ACS in China. Accordingly, this study compared the safety and efficacy between fondaparinux and nadroparin in patients with NSTE-ACS.

METHODSIn this prospective, randomized, open-label, and single center study, a total of 300 patients with NSTE-ACS were randomized to receive either fondaparinux (group F, n = 150, 2.5 mg/d) or nadroparin (group N, n = 150, 0.1 ml/10 kg q12 h) for a mean of 4 days. The primary safety endpoint was the incidence of major or minor bleeding at 9 days that was not related to coronary artery bypass grafting (CABG). The primary efficacy endpoints included death, myocardial infarction, or recurrent ischemia at 9 days. All patients underwent a 180-day follow-up.

RESULTSBaseline characteristics were well matched between the two groups. There was a non-significant 28% relative risk reduction in the primary safety endpoint in group F compared with group N (4.7% vs. 6.7%, HR 0.72, 95%CI 0.42-1.65, P = 0.38). The primary efficacy endpoint was 8.0% in group F and 10.0% in group N (HR, 0.82, 95%CI 0.54-1.71, P = 0.49). The composite of the safety and efficacy endpoints at 9 days (10.0% vs. 16.0%, HR 0.61, 95%CI 0.31-1.10, P = 0.10), 30 days (14.0% vs. 17.9%, HR 0.72, 95%CI 0.47-1.16, P = 0.21), or 180 days (18.7% vs. 27.3%, HR 0.65, 95%CI 0.38-1.11, P = 0.11) showed a non-significant trend toward a lower value in group F.

CONCLUSIONFondaparinux resulted in a nonsignificant risk reduction in patients with NSTE-ACS in both bleeding and ischaemic events during short- and long-term follow-up compared with nadroparin.

Acute Coronary Syndrome ; drug therapy ; Aged ; Anticoagulants ; adverse effects ; therapeutic use ; Female ; Fibrinolytic Agents ; adverse effects ; therapeutic use ; Humans ; Male ; Middle Aged ; Nadroparin ; adverse effects ; therapeutic use ; Polysaccharides ; adverse effects ; therapeutic use ; Treatment Outcome

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

Prostate cancer is a common malignant tumor in male patients. It is of great clinical significance to explore the pathogenesis of prostate cancer and find suitable therapeutic targets. NR4A3 is derived from the nuclear hormone receptor superfamily of steroids, and NR4A3 plays an important role in the malignant progression of a variety of tumors. However, its role in prostate cancer has not yet been elucidated. Therefore, this project intends to investigate the role of NR4A3 in prostate cancer and screen for miRNAs that target NR4A3, which may help find potential target for the diagnosis and treatment of prostate cancer. The GEPIA website predicts that NR4A3 is under-expressed in prostate cancer tissues, and qRT-PCR data confirmed downregulation of NR4A3 in prostate cancer cells (P<0. 01). CCK8 and clone formation experiments show that overexpression of NR4A3 can significantly inhibit the viability, the number and size of colonies of prostate cancer cells (P < 0. 01). The bioinformatics website predicts that NR4A3 may be the target gene of miR-20a, and qRT-PCR showed that miR-20a expression was elevated in prostate cancer cells (P<0. 01). Furthermore, dual luciferase reporter gene experiment confirmed that miR-20a can target two sites of 3′-UTR of NR4A3 (P<0. 05, P<0. 001). Western blot results showed that miR-20a can inhibit the expression of NR4A3. CCK8 experiments further found that miR-20a inhibitor can significantly reduce the viability of prostate cancer cells(P<0. 05), while miR-20a mimic has the opposite effect (P<0. 05, P<0. 01). CCK8 and clone formation experiments showed that when co-transfected with miR-20a mimic and pcDNA3. 1-NR4A3 recombinant plasmids, up-regulation of NR4A3 could partially offset the viability, the number and size of colonies of PC3 cells promoted by miR-20a mimic (P <0. 05). In summary, miR-20a promotes the proliferation of prostate cancer cells by targeting NR4A3.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.