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Rhizoma coptidis (CR) is traditionally used for treating gastrointestinal diseases. Wine-processed CR (wCR), zingiber-processed CR (zCR), and evodia-processed CR (eCR) are its major processed products. However, the related study of their specific mechanisms is very limited, and they need to be further clarified. The aim of this study is to compare the intervening mechanism of wCR/zCR/eCR on rats via faecal metabolomics and 16S rDNA gene sequencing analysis. First, faecal samples were collected from the control and CR/wCR/zCR/eCR groups. Then, a metabolomics analysis was performed using UHPLC-Q/TOF-MS to obtain the metabolic profile and significantly altered metabolites. The 16S rDNA gene sequencing analysis was carried out to analyze the composition of gut microbiota and screen out the significantly altered microbiota at the genus level. Finally, a pathway enrichment analysis of the significantly altered metabolites via the KEGG database and a functional prediction of relevant gut microbes based on PICRUSt2 software were performed in combination. Together with the correlation analysis between metabolites and gut microbiota, the potential intervening mechanism of wCR/zCR/eCR was explored. The results suggested that wCR played a good role in maintaining immune homeostasis, promoting glycolysis, and reducing cholesterol; zCR had a better effect on protecting the integrity of the intestinal mucus barrier, preventing gastric ulcers, and reducing body cholesterol; eCR was good at protecting the integrity of the intestinal mucus barrier and promoting glycolysis. This study scientifically elucidated the intervening mechanism of wCR/zCR/eCR from the perspective of faecal metabolites and gut microbiota, providing a new insight into the processing mechanism research of Chinese herbs. [ABSTRACT FROM AUTHOR]

This paper provides a novel method to synchronize uncertain fractional-order chaotic systems with external disturbance via fractional terminal sliding mode control. Based on Lyapunov stability theory, a new fractional-order switching manifold is proposed, and in order to ensure the occurrence of sliding motion in finite time, a corresponding sliding mode control law is designed. The proposed control scheme is applied to synchronize the fractional-order Lorenz chaotic system and fractional-order Chen chaotic system with uncertainty and external disturbance parameters. The simulation results show the applicability and efficiency of the proposed scheme. [ABSTRACT FROM AUTHOR]

Abstract: Ischemic stroke is a medical emergency triggered by a rapid reduction in blood supply to localized portions of the brain, usually because of thrombosis or embolism, which leads to neuronal dysfunction and death in the affected brain areas. Leptin is generally considered to be a strong and quick stress mediator after injuries. However, whether and how peripherally administered leptin performs neuroprotective potency in cerebral stroke has not been fully investigated. It has been reported that CGRP8-37, an antagonist of the CGRP receptor, could reverse the protective effect of leptin on rats with CIP (caerulein-induced pancreatitis). However, the question remains: are leptin and CGRP associated in cerebral ischemia/reperfusion injury? The present study attempted to evaluate the relationship between CGRP expression and leptin neuroprotective effects (1mg/kg in 200μL normal saline, i.p.) on focal cerebral ischemia/reperfusion injury in mice and the protective effect of leptin (500μg/L) on neurons during hypoxia/reoxygenation injury. Peripheral administration of leptin alleviated injury-evoked brain damage by promoting CGRP expression, improving regional cerebral blood flow, and reducing local infarct volume and neurological deficits. Furthermore, leptin also promoted bcl-2 expression and suppressed caspase-3 in vivo and vitro after injury. Administration of CGRP8-37 (4×10−8 mol/L) partly abolished the beneficial effects of leptin, and restored the normal expression levels of bcl-2 and caspase-3 in neurons, which indicated that leptin-induced protection of neurons was correlated with release of CGRP. These results indicate that the neuroprotective effect of leptin against cerebral ischemia/reperfusion injury may be strongly relevant to the increase of CGRP expression. [Copyright &y& Elsevier]

1. Metformin is one of the most commonly used drugs for the treatment of Type 2 diabetes. Accumulating evidence suggests that metformin also has cardioprotective effects. In the present study, we investigated the cardioprotective effects of metformin and the mechanisms involved. 2. A rat model of chronic heart failure was established by permanent left coronary artery occlusion. Heart failure rats were randomly divided into four groups: (i) a saline-treated group given 4 mL/kg day via intragastric gavage; (ii) a metformin-treated group, given 100 mg/kg metformin once daily via intragastric gavage; (iii) a group treated with 5 mg/kg 5′-aminoimidazole-4-carboxyamide-ribonucleoside (AICAR), an AMP-activated protein kinase (AMPK) agonist, every second day; and (iv) a group treated with 100 mg/kg per day metformin + 20 mg/kg, i.p., compound C (an AMPK antagonist). After 4 weeks treatment, echocardiography was used to assess left ventricular (LV) dimensions and function. Expression of AMPK, endothelial nitric oxide synthase (eNOS) and transforming growth factor (TGF)-β1 was determined by reverse transcription-polymerase chain reaction and western blot analysis. 3. Metformin administration significantly improved cardiac function and LV remodelling, as evidenced by increases in LV systolic pressure and LV ejection fraction and decreases in LV end-diastolic diameter and LV end-systolic diameter. These beneficial effects of metformin were associated with increased AMPK and eNOS phosphorylation, as well as reductions in insulin, TGF-β1, basic fibroblast growth factor and tumour necrosis factor-α levels in the circulation and/or myocardium. 4. The results indicate that chronic low-dose metformin confers significant cardioprotective effects against chronic heart failure by activating the AMPK-eNOS pathway. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the effect of atorvastatin on the serum levels of tumor necrosis factor alpha (TNF-αα) and interleukin-1beta (IL-1ββ) following acute pulmonary embolism (PE). Forty New Zealand white rabbits were divided into control and atorvastatin groups. Acute PE was created by injection of autologous blood clots into the femoral vein. Enzyme-linked immunosorbent assay was used to measure TNF-αα and IL-1ββ. At baseline, there was no significant difference in serum TNF-αα (10.6 ±± 1.3 versus 11.2 ±± 1.9 pg/mL; P > .05) or IL-1ββ (8.2 ±± 1.0 versus 8.6 ±± 0.9 pg/mL; P > .05) between the control group and the atorvastatin group. In both groups, there was a significant increase in the serum TNF-αα and IL-1ββ following acute PE. However, the levels of serum TNF-αα and IL-1ββ in the atorvastatin group was significantly lower than in the control group following PE ( P < .01). The authors conclude that acute PE is associated with a significant increase in serum proinflammatory factors TNF-αα and IL-1ββ. Pretreatment with atorvastatin diminished the increase in TNF-αα and IL-1ββ. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to elucidate the mechanism of beraprost sodium (BPS) in the intervention of myocardial fibrosis after myocardial infarction (MI) through glycogen synthase kinase‐3β (GSK‐3β) and to provide new ideas for intervention in myocardial fibrosis. Materials and Methods: MI model rats given BPS and cardiac fibroblasts (CFs) treated with BPS and TGF‐β. HE staining and Masson staining were used to detect the pathological changes of myocardial tissue. Fibrotic markers were detected by immunohistochemical staining. The expressions of GSK‐3β, cAMP response element binding protein (CREB), and p‐CREB were analyzed by qPCR and western blot analysis. EDU staining was used to detect the proliferation of CFs. The promoter activity of GSK‐3β was detected by luciferase assay. Chromatin immunoprecipitation assay was used to detect the binding levels of GSK‐3β promoter and Y‐box binding protein 1 (YBX1). The levels of intracellular cyclic adenosine monophosphate (cAMP) were analyzed by enzyme‐linked immunosorbent assay (ELISA). Results: After operation, BPS improved myocardial fibrosis and upregulated GSK‐3β protein expression in male SD rats. BPS can down‐regulate α‐smooth muscle actin (α‐SMA) level and up‐regulate GSK‐3β protein expression in CFs after TGF‐β stimulation. Furthermore, GSK‐3β knockdown can reverse the effect of BPS on TGF‐β‐activated CFs, enhance α‐SMA expression, and promote the proliferation of CFs. BPS could regulate GSK‐3β expression by promoting the binding of GSK‐3β promoter to YBX1. BPS induced upregulation of p‐CREB and cAMP, resulting in reduced fibrosis, which was reversed by the knockdown of GSK‐3β or prostaglandin receptor (IPR) antagonists. Conclusion: BPS treatment increased the binding of YBX1 to the GSK‐3β promoter, and GSK‐3β protein expression was upregulated, which further caused the upregulation of p‐CREB and cAMP, and finally inhibited myocardial fibrosis. [ABSTRACT FROM AUTHOR]

This article, titled "[Retracted] Exogenous hydrogen sulfide protects against high glucose-induced apoptosis and oxidative stress by inhibiting the STAT3/HIF-1α pathway in H9c2 cardiomyocytes," was published in Experimental & Therapeutic Medicine in 2019. However, it has since been retracted due to concerns raised by a reader. The reader pointed out that certain data in the article appeared to have been previously published by different authors at different research institutes. The authors were asked for an explanation but did not respond. The editor of the journal has apologized for any inconvenience caused. [Extracted from the article]

Purpose: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is involved in the pathogenesis of atherosclerosis, especially in advanced plaques. In the present study, the abilities of darapladib, a selective Lp-PLA(2) inhibitor, and lentivirus-mediated Lp-PLA(2) silencing on inflammation and atherosclerosis in apolipoprotein E-deficient mice were compared.Methods: Apolipoprotein E-deficient mice were fed on a high-fat diet and a constrictive collar was placed around the left carotid artery to induce plaque formation. The mice were randomly divided into control, negative control (NC), darapladib and RNA interference (RNAi) groups. Eight weeks after surgery, lentivirus-mediated RNAi construct or darapladib were used to decrease the expression of Lp-PLA(2). Plaques were collected five weeks later for histological analysis. Inflammatory gene expression in the atherosclerotic lesions were then determined at the mRNA and protein level.Results: The expression of pro-inflammatory cytokines was significantly reduced in the treatment group, compared to nontreatment group, whereas the plasma concentration of anti-inflammatory cytokines increased markedly. Moreover, our results demonstrated a significant reduction in plaque lipid content, as well as a rise in collagen content following Lp-PLA(2) inhibition. Interestingly, when comparing the two methods of Lp-PLA(2) inhibition, animals treated with Lp-PLA(2) RNAi were found to exhibit lower plaque areas and enhanced improvement of plaque stability as compared with animals treated with darapladib. Darapladib had no attenuating effect on atherosclerotic plaque area. These therapeutic effects were independent of plasma lipoprotein levels.Conclusions: Lp-PLA(2) inhibition by darapladib or lentivirus-mediated RNAi ameliorated inflammation and atherosclerosis in apolipoprotein E-deficient mice. The effect was more prominent in the RNAi group. [ABSTRACT FROM AUTHOR]

Leptin is a multifunctional hormone produced by the ob gene and is secreted by adipocytes that regulate food intake and energy metabolism. Numerous studies demonstrated that leptin is a novel neuroprotective effector, however, the mechanisms are largely unknown. Herein, we demonstrate the protective activities of leptin after ischemic stroke and provide the first evidence for the involvement of the connexin 43 (Cx43) in leptin-mediated neuroprotection. We found that leptin treatment reduces the infarct volume, improves animal behavioral parameters, and inhibits the elevation of Cx43 expression in vivo. In vitro, leptin reverses ischemia-induced SY5Y and U87 cells Cx43 elevation, secreted glutamate levels in medium and SY5Y cell death, these roles could be abolished by leptin receptor blocker. Additionally, leptin administration upregulated the extracellular signal-regulated kinase1/2 (ERK1/2) phosphorylation. Moreover, ERK1/2 inhibitors pretreatment reversed the effects of leptin on Cx43 expression, glutamate levels and cell apoptosis. In conclusion, the present study demonstrated that leptin can reduce the Cx43 expression and cell death both in vivo and in vitro via ERK1/2 signaling pathway. This result provides a novel regulatory signaling pathway of the neuroprotective effects of leptin and may contribute to ischemic brain injury prevention and therapy. [ABSTRACT FROM AUTHOR]

In order to improve the calibration precision of 6DOF parallel mechanism, a calibration method based on external coordinate measurement is presented. The position and attitude informations of the parallel mechanism are acquired using common measuring devices and the residual equations with uniform measure are constructed. These equations can ensure the identifiability of each geometry parameter's, so no special auxiliary calibration equipments or redundant sensors are required. From the residual equations, the estimated values of geometry parameters are obtained by optimization method, and the ideal parameters are replaced by them for the parallel mechanism inverse kinematics calculation of to realize the error compensation. The simulation results show that this method can decrease the effect of measure noise, and the kinematics accuracy after calibration can reach the same order of magnitude as measurement noise since the errors of parallel mechanism's are not usually cumulated. The calibration accuracy is improved more than 5 times after error compensation by using the method. [ABSTRACT FROM AUTHOR]

Purpose: Elevation of the levels of myocardial biomarkers after percutaneous coronary intervention (PCI) has prognostic value in patients with coronary heart disease. We explored the relationship between elevation of the serum level of cardiac troponin T (cTnT) after PCI and platelet aggregation rate and coronary plaque composition. Methods: Eighty patients with unstable angina pectoris underwent PCI and were divided into two groups according to serum cTnT level 24 hours after PCI: group I (cTnT ≥2 times the normal level) and group II (cTnT <2 times the normal level). Coronary plaque composition was measured with virtual histology-intravascular ultrasound. Platelet aggregation rate was detected immediately before and 24 hours after PCI. Results: Compared with the patients in group II, patients in group I showed more unstable plaques, a larger necrotic core area (20.88 ± 8.04% vs. 15.31 ± 5.48%, P < 0.05), higher platelet aggregation rate (51.47 ± 12.72% vs. 44.78 ± 13.29%, P < 0.05), and longer stents. The serum cTnT level 24 hours after PCI was positively correlated with the necrotic core area. Conclusions: In patients with unstable angina pectoris, a large necrotic core, high rate of platelet aggregation, and stent length are predictors of cTnT elevation after PCI. (J Interven Cardiol 2012;25:433-438) [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the efficacy and safety of long-term (>18 months) dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). A total of 3205 coronary artery disease (CAD) patients after PCI from CORFCHD-PCI, a retrospective cohort study (Identifier: ChiCTR-ORC-16010153), were divided into two groups: monotherapy of aspirin or clopidogrel group (SAPT group, n = 2188 and DAPT group, n = 1017) according to whether to discontinue DAPT 18 months after PCI. After propensity matching analysis (PSM), we included 1017 patients in the DAPT group and 1017 patients in the SAPT group. All the patients were followed-up for at least 18 months and the longest follow-up time is 120 months. The primary endpoint was the incidence of major adverse cardiac events (MACEs). The secondary endpoints were the incidence of major adverse cardiovascular and cerebrovascular events (MACEEs) and bleeding events. We also selected 178 patients for detection of claudin-3 and intestinal fatty acid-binding protein and 58 patients for 16s RNA sequencing of whole blood. The incidences of MACEs (13.9% vs. 9.0%, p = 0.001) and MACCEs (16.3% vs. 10.0%, p < 0.001) were significantly increased in the DAPT group compared to the SAPT group. We also found DAPT increased the bleeding events compared to SAPT (4.6% vs. 2.9%, p = 0.048). Multivariate Cox regression analyses showed that in the DAPT group, cumulative risk of MACCEs increased 1.797 times (HR = 1.797, 95%CI: 1.429–2.226, p < 0.001), MACEs increased 1.737 times (HR = 1.737, 95%CI: 1.360–2.218, p < 0.001) and the bleeding events increased 2.129 times (HR = 2.129, 95%CI: 1.388–3.266, p = 0.001) compared to the SAPT group. We also found the plasma concentrations of claudin-3 and intestinal fatty acid-binding protein (I-FABP) were significantly higher in patients in the DAPT group compared with patients in the SAPT group (both p < 0.001). Correspondingly, the abundance of blood intestinal bacteria in the DAPT group was significantly increased compared to that in the SAPT group (p < 0.001). Furthermore, high-throughput metabolomics analysis suggested that serum level of ceramide (d18:1/16:0) and Neu5Ac was significantly increased in the DAPT group compared to the SAPT group (both p < 0.001). The present study suggests that long-term dual antiplatelet therapy longer than 18 months significantly increases the incidence of both ischemic events and bleeding events after PCI. This preliminary study also indicates that long-term DAPT causes intestinal injury, which induces translocation of intestinal bacteria into the bloodstream. [Display omitted] • This study suggested long-term DAPT increased bleeding events and ischemic events. • This study provided a basis for shortening duration of DAPT in patients who underwent PCI. • Long-term DAPT increasing ischemic events and bleedings may be associated with intestinal injury. • Important differences were found in the blood microbiome of patients with long-term DAPT. • Blood bacterial DNA concentration, ceramide (d18:1/16:0), and Neu5Ac increased in long-term DAPT patients. [ABSTRACT FROM AUTHOR]

Background: Alanine aminotransferase (ALT) is referred as liver transaminase and predominantly expressed by hepatocytes. Previous evidences showed that high levels of ALT were reversely associated with short- and long-term outcomes in patients with myocardial infarction. Besides, low lymphocyte has been demonstrated to be significantly correlated with adverse clinical outcomes in coronary artery disease (CAD). However, evidences about the relationship between ALT-to-lymphocyte ratio (ALR) and outcomes in CAD patients with normal liver function are limited. The aim of this study was to assess the relationship between ALR and clinical outcomes in patients with CAD.Methods: This is a retrospective cohort study, and a total of 3561 patients were enrolled in Clinical Outcomes and Risk Factors of Patients with CAD after percutaneous coronary intervention (PCI), from January 2013 to December 2017. After excluding patients with liver dysfunction, we finally enrolled 2714 patients. These patients were divided into two groups according to ALR value: the lower group (ALR < 14.06, n = 1804) and the higher group (ALR ≥ 14.06, n = 910). The average follow-up time was 37.59 ± 22.24 months.Results: We found that there were significant differences between the two groups in the incidence of all-cause mortality (ACM) (P < 0.001) and cardiac mortality (CM) (P=0.010). Kaplan-Meier survival analysis suggested that CAD patients with higher ALR tended to have an increased accumulated risk of ACM and CM (log rank P < 0.001 and P=0.006, respectively). Multivariate Cox regression analysis showed that ALR was an independent predictor of ACM (hazard ratio (HR) = 2.017 (95% confidence interval (CI): 1.289-3.158), P=0.002) and CM (HR = 1.862 (95% CI: 1.047-3.313), P=0.034). We did not find significant difference in the incidence of major adverse cardiovascular events (MACEs) and major adverse cardiovascular and cerebrovascular events (MACCEs) between the two groups after adjustments of confounders.Conclusion: Our results indicate that ALR is an independent predictor of long-term adverse outcomes in CAD patients who underwent PCI. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S), an endogenous gasotransmitter, possesses multiple physiological and pharmacological properties including anti-apoptotic, anti-oxidative stress and cardiac protective activities in diabetic cardiomyopathy. An increasing body of evidence has suggested that signal transducer and activator of transcription 3 (STAT3) has beneficial effects in the heart. However, the effect of diabetes on the phosphorylation or activation of cardiac STAT3 appears to be controversial. The present study was designed to investigate the precise function of the STAT3/hypoxia-inducible factor-1α (HIF-1α) signaling pathway in high glucose (HG)-induced H9c2 cardiomyocyte injury and the function of the STAT3/HIF-1α pathway in the cardioprotective action of H2S. The results revealed that GYY4137 pretreatment substantially ameliorated the HG-induced decrease in cell viability and the increase in lactate dehydrogenase (LDH) release in H9c2 cells. Additionally, HG treatment resulted in the upregulation of the phosphorylated (p)-STAT3/STAT3 ratio and HIF-1α protein expression in H9c2 cells, indicating that the activation of the STAT3/HIF-1α pathway was induced by HG. STAT3/HIF-1α pathway inhibition induced by transfection with STAT3 small interfering (si)-RNA attenuated the HG-induced downregulation of cell viability and the upregulation of LDH release. Furthermore, STAT3 siRNA transfection and GYY4137 pretreatment combined attenuated HG-induced apoptosis as illustrated by the decrease in the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, caspase-3 activity, apoptosis ratio and BCL2 associated X, apoptosis regulator/BCL2 apoptosis regulator ratio in H9c2 cells. In addition, STAT3 siRNA transfection and GYY4137 blocked HG-induced oxidative stress as evidenced by the decrease in reactive oxygen species generation, malondialdehyde content and NADPH oxidase 2 expression, and the increase in superoxide dismutase activity and glutathione level. Notably, GYY4137 pretreatment was revealed to reduce the p-STAT3/STAT3 ratio and HIF-1α protein expression, resulting in the inhibition of the STAT3/HIF-1α signaling pathway in HG-treated H9c2 cells. Altogether, the present results demonstrated that H2S mitigates HG-induced H9c2 cell damage, and reduces apoptosis and oxidative stress by suppressing the STAT3/HIF-1α signaling pathway. [ABSTRACT FROM AUTHOR]

Background. The relationship between heart rate in CAD patients who underwent percutaneous coronary intervention (PCI) and had long-term outcomes over up to 10 years of follow-up has not been investigated. Methods. All patients were from the CORFCHD-PCI, a retrospective cohort study that included a total of 6050 CAD patients who underwent PCI from January 2008 to December 2016. One patient was excluded due to a lack of heart rate data. Ultimately, 6049 patients were enrolled. The primary outcome was long-term mortality after PCI. Results. Patients were divided into 5 groups according to heart rate quintiles: 1st quintile (heart rate <66 beats/min; n=1123), 2nd quintile (heart rate ≥66 beats/min to 72 beats/min; n=1010), 3rd quintile (heart rate ≥72 beats/min to 78 beats/min; n=1442), 4th quintile (heart rate ≥78 beats/min to 84 beats/min; n=1211), and 5th quintile (heart rate ≥84 beats/min; n=1263). After multivariate Cox regression analyses, the respective risks of ACM, CM, and MACEs were increased 79.1% (hazard risk (HR) = 1.791, 95% CI: 1.207–2.657, P=0.004), 56.9% (HR = 1.569, 95% CI: 1.019–2.416, P=0.041), and 25.5% (HR = 1.255, 95% CI: 0.990–1.590, P=0.060) in the 4th quintile and 98.7% (HR = 1.987, 95% CI: 1.344–2.937, P=0.001), 98.8% (HR = 1.988, 95% CI: 1.310–3.016, P<0.001), and 0.36.1% (HR = 1.361, 95% CI: 1.071–1.730, P=0.012) in the 5th quintile compared with those in the 1st quintile. Patients with a heart rate of ≥80 beats/min had 89.4%, 115.2%, and 39.1% increased risk of ACM, CM, and MACEs, respectively, compared to those patients with a heart rate of <80 beats/min. Conclusion. The present study indicated that the resting heart rate is an independent predictor of adverse long-term outcomes in CAD patients who underwent PCI. [ABSTRACT FROM AUTHOR]

Objective: Myocyte enhancer factor-2A (MEF 2A) has been shown to be involved in atherosclerotic lesion development, but its role in preexisting lesions is still unclear. In the present study we aim to assess the role of MEF 2A in the progression of pre-existing atherosclerosis. Methods: Eighty apolipoprotein E-deficient mice (APOE KO) were randomly allocated to control, scramble and MEF 2A RNA interference (RNAi) groups, and constrictive collars were used to induce plaque formation. Six weeks after surgery, lentiviral shRNA construct was used to silence the expression of MEF 2A. Carotid plaques were harvested for analysis 4 weeks after viral vector transduction. Inflammatory gene expression in the plasma and carotid plaques was determined by using ELISAs and real-time RT-PCR. Results: The expression level of MEF 2A was significantly reduced in plasma and plaque in the RNAi group, compared to the control and NC groups, whereas the expression level of pro-inflammatory cytokines was markedly increased. Silencing MEF 2A using lentiviral shRNA significantly reduced the plaque collagen content and fibrous cap thickness, as well as increased plaque area. However, silencing MEF 2A had no obvious effect on plaque lipid content. Conclusions: Lentivirus-mediated MEF 2A shRNA accelerates inflammation and atherosclerosis in APOE KO mice, but has no effect on lipoprotein levels in plasma. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggest the higher the red blood cell distribution width (RDW) the greater the risk of mortality in patients with coronary artery disease (CAD). However, the relationship between RDW and long-term outcome in CAD patients undergoing percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) remains unclear. This study was designed to evaluate the long-term effect of RDW in patients treated with drug-eluting stent for CAD. Methods: In total of 2169 non-anemic patients (1468 men, mean age 60.2±10.9 years) with CAD who had undergone successful PCI and had at least one drug-eluting stent were included in this study. Patients were grouped according to their baseline RDW: Quartile 1 (RDW<12.27%), Quartile 2 (12.27%≤RDW<13%), Quartile 3 (13%≤RDW<13.5%), and Quartile 4 (RDW≥13.5). Results: The incidence of in-hospital mortality and death or myocardial infarction was significantly higher in Quartiles 3 and 4 compared with Quartile 1 (P<0.05). After a follow-up of 29 months, the incidence of all-cause death and stent thrombosis in Quartile 4 was higher than in Quartiles 1, 2, and 3 (P<0.05). The incidence of death/myocardial infarction/stroke and cardiac death in Quartile 4 was higher than in Quartiles 1 and 2 (P<0.05). Multivariate Cox regression analysis showed that RDW was an independent predictor of all-cause death (hazard ratio (HR) = 1.37, 95% confidence interval (CI) = 1.15–1.62, P<0.001) and outcomes of death/myocardial infarction/stroke (HR = 1.21, 95% CI = 1.04–1.39, P = 0.013). The cumulative survival rate of Quartile 4 was lower than that of Quartiles 1, 2, and 3 (P<0.05). Conclusion: High RDW is an independent predictor of long-term adverse clinical outcomes in non-anemic patients with CAD treated with DES. [ABSTRACT FROM AUTHOR]

Background: MiRNA primarily acts to repress gene expression at the post-transcriptional level through imperfect complementarity of its 5′ region to the “seed site” in the 3′ untranslated region of target mRNAs, with its “3′–supplementary site” and “center site” also playing important roles under certain circumstances. The aim of this study was to test if artificial miRNA mimics (miR-Mimics) that are designed to target the “centered sites” without “seed sites” complementarity are able to repress gene expression as natural miRNAs. Methods: We designed miR-Mimics carrying centered-site matches (CS–miR-Mimics) or seed-site matches (SS–miR-Mimics) and siRNA to two antiapoptotic genes BCL2 and AKT1. We tested the gene targeting of these constructs using real-time RT-PCR and Western blot to quantify mRNA and protein levels of BCL2 and AKT1, respectively, luciferase reporter gene assay to investigate the interaction between miR-Mimics and their target sites, and cell survival assay to study the functional outcomes of the miR-Mimics. Results: We found that CS-miR-Mimic, SS-miR-Mimic and siRNA, all down regulated the mRNA and protein levels of their cognate target BCL2 or AKT1 in a concentration-dependent manner. Luciferase reporter gene assay further confirmed the functional interactions of CS–miR-Mimic, SS-miR-Mimic and siRNA with their target sites. We then observed that the miR-Mimics and siRNAs were all able to induce cell death, as indicated by the reduced survival rate of cells. Conclusions: We have provided evidence for the feasibility of CS–miR-Mimics for post-transcriptional repression of genes, which can be designed to have reduced numbers of seed type off-target sites compared to the number of target sites from an average endogenous seed–site miRNA. CS–miR-Mimics may be a novel approach for miRNA research requiring miRNA gain-of-function. [ABSTRACT FROM AUTHOR]

Aiming at load simulating problem of the thrust vector control (TVC) system in launch vehicles, a new load simulator structure and its mathematical model are presented. The influence of main parameters on system's dynamic performance is analyzed by simulation. Building a prototype experiment system, multiple DOF load property is showed in a sweep frequency test. Simulation and experiment verify the feasibility of this load simulator structure, which lay a foundation for optimizing design parameters of the thrust vector servo mechanism and developing load simulators of heavy launch vehicles' servo systems. [ABSTRACT FROM AUTHOR]

1. Inhibiting the renin–angiotensin–aldosterone system prevents left ventricular (LV) remodelling after myocardial infarction (MI). 2. The present study was designed to assess the effects of a combination of perindopril and losartan on LV remodelling, cardiac function and serum procollagen type III amino terminal peptide (PIIINP) levels in patients with acute MI. 3. Patients with anterior MI were divided into three groups: (i) MI + perindopril; (ii) MI + losartan; and (iii) MI + perindopril + losartan. After successful intervention therapy, perindopril (2–4 mg daily), losartan potassium (25–50 mg daily) or their combination were administered. All patients received aspirin, clopidogrel and statins, and some patients were given beta-blockers, nitrate and a platelet glycoprotein IIb/IIIa receptor antagonist. Three months later, LV dimensions and LV ejection fraction (LVEF) were measured by ultrasonography. Plasma B-type natriuretic peptide (BNP), serum C-reactive protein (CRP) and PIIINP levels were evaluated using enzyme-linked immunosorbent assay or radioimmunoassay. 4. The baseline characteristics of the three groups were the same. Three months after the initiation of therapy, all patients showed decreased CRP, increased BNP and PIIINP levels and LV dilation and dysfunction. Compared with the two monotherapy groups, patients in the combination group showed significantly lower CRP, BNP and PIIINP levels, less LV dilation and higher LVEF. Serum PIIINP levels were positively correlated with CRP levels ( r = 0.597; P < 0.01) and LV end-diastolic volume index ( r = 0.543; P < 0.01) and were negatively correlated with LVEF ( r = –0.565; P < 0.01). 5. For patients with acute MI, combination treatment with perindopril and losartan significantly inhibited LV remodelling and improved LV function. Inhibition of myocardial interstitial fibrosis may be part of the underlying mechanism. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The aim of this study was to evaluate the expression and clinical significance of leptin in lung cancer. Methods: 126 patients with lung cancer ranged from 30 to 83years of age were studied. Serum leptin levels were determined by ELISA. The mRNA and protein levels of leptin in normal and lung cancer tissues were measured by RT-PCR and immunohistochemistry. The relationships between leptin levels and clinicopathological factors were evaluated by Wilcoxon rank sum or Kruskal–Wallis H test. Results: Serum leptin levels in lung cancer patients were significantly higher compared to those in controls and leptin expression in lung cancer tissue was markedly increased than that in normal lung tissue (both P <0.050). Conclusions: Determination of leptin levels might provide useful predictive information for lung cancer. [Copyright &y& Elsevier]

In this study, we developed a pro-endothelial-functionalization surface by immobilizing a natural factors-loaded nanoparticle, exosome, onto the poly-dopamine (PDA) coated materials via electrostatic binding. • A novel PDA/Exosome coating was successfully prepared onto the cardiovascular biomaterial. • The PDA/Exosome coating could enhance the endothelial cell growth, CD31 expression and NO release. • The PDA/Exosome coating could regulate SMC into contractile phenotype and macrophage into M2 phenotype. • The PDA/Exosome coating could reduce hyperplasia of the implant. • The PDA/Exosome coating regulated the endothelial cell behavior by entering into cells. Stent intervention as available method in clinic has been widely applied for cardiovascular disease treatment for decades. However, the restenosis caused by late thrombosis and hyperplasia still limits the stents long-term application, and the essential cause is usually recognized as endothelial functionalization insufficiency of the stent material surface. Here, we address this limitation by developing a pro-endothelial-functionalization surface that immobilized a natural factors-loaded nanoparticle, exosome, onto the poly-dopamine (PDA) coated materials via electrostatic binding. This PDA/Exosome surface not only increased the endothelial cells number on the materials, but also improved their endothelial function, including platelet endothelial cell adhesion molecule-1 (CD31) expression, cell migration and nitric oxide release. The pro-inflammation macrophage (M1 phenotype) attachment and synthetic smooth muscle cell proliferation as the interference factors for the endothelialization were not only inhibited by the PDA/Exosome coating, while the cells were also regulated to anti-inflammation macrophage (M2 phenotype) and contractile smooth muscle cell, which may contribute to endothelialization. Thus, it can be summarized this method has potential application on surface modification of cardiovascular biomaterials. [ABSTRACT FROM AUTHOR]

Background: It has been confirmed that the triglyceride to high-density lipoprotein cholesterol ratio (THR) is associated with insulin resistance and metabolic syndrome. However, to the best of our knowledge, only a few studies with small sample sizes have investigated the relationship between THR and coronary artery disease (CAD). Therefore, we aimed to assess the correlation between the THR and long-term mortality in patients with CAD after undergoing percutaneous coronary intervention (PCI) in our study that enrolled a large number of patients. Methods: A total of 3269 post-PCI patients with CAD were enrolled in the CORFCHD-ZZ study from January 2013 to December 2017. The mean follow-up time was 37.59 ± 22.24 months. Patients were divided into two groups according to their THR value: the lower group (THR < 2.84, n = 1232) and the higher group (THR ≥ 2.84, n = 2037). The primary endpoint was long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). Results: In our study, ACM occurred in 124 patients: 30 (2.4%) in the lower group and 94 (4.6%) in the higher group (P = 0.002). MACEs occurred in 362 patients: 111 (9.0%) in the lower group and 251 (12.3%) in the higher group (P = 0.003). The number of MACCEs was 482: 152 (12.3%) in the lower group and 320 (15.7%) in the higher group (P = 0.008). Heart failure occurred in 514 patients: 89 (7.2%) in the lower group and 425 (20.9%) in the higher group (P < 0.001). Kaplan–Meier analyses showed that elevated THR was significantly related to long-term ACM (log-rank, P = 0.044) and the occurrence of heart failure (log-rank, P < 0.001). Multivariate Cox regression analyses showed that the THR was an independent predictor of long-term ACM (adjusted HR = 2.042 [1.264–3.300], P = 0.004) and heart failure (adjusted HR = 1.700 [1.347–2.147], P < 0.001). Conclusions: An increased THR is an independent predictor of long-term ACM and heart failure in post-PCI patients with CAD. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the levels of interleukin-33 (IL-33) and interleukin-6 (IL-6) in patients with acute coronary syndrome or stable angina.Methods: Serum IL-33 and IL-6 were measured with Enzyme Linked Immuosorbent Assay (ELISA) in patients with acute coronary syndrome (ACS, n=40), and stable angina pectoris (SAP, n=43). IL-33 and IL-6 were also determined in 30 healthy subjects (control group).Results: The serum level of IL-33 in the ACS group (78.60±44.84 ng/L) was lower than in the SAP (102.58±37.21 ng/L, P<0.01) or control groups (130.24±10.17 ng/L, P<0.01). The serum level of IL-6 in the ACS group (39.90±12.64 ng/L) was higher than in the SAP (18.68±11.89 ng/L, P<0.05) or control groups (6.28±17.72 ng/L, P<0.05). There were no differences in serum levels of IL-33 and IL-6 among the single-, double- and triple-vessel lesion groups. IL-33 and IL-6 levels were negatively correlated with each other in the ACS (r=-0.871, P<0.01) and SAP groups (r=-0.788, P<0.01).Conclusion: The serum level of IL-33 was lower in patients with ACS or SAP and was negatively correlated with the serum level of IL-6. Thus, IL-33 and IL-6 may be used as biomarkers for evaluating inflammatory response and severity of coronary heart disease in patients with ACS or SAP. [ABSTRACT FROM AUTHOR]