Platelet-to-lymphocyte ratio relates to poor prognosis in elderly patients with acute myocardial infarction.

BACKGROUND: The platelet to lymphocyte ratio (PLR) is a novel biomarker to predict the prognosis of acute myocardial infarction (AMI) patients. AIM: The study aimed to evaluate the in-hospital outcomes of elderly patients with AMI and assessed the prognostic value of PLR on in-hospital adverse events. METHODS: A total of 1,001 patients were divided into an older group (n = 560) and a younger group (n = 441) based on age ≥ 60 years and successfully underwent primary percutaneous coronary intervention (PCI) within 12 h after presentation. Total white blood cells (WBCs), neutrophils, lymphocytes, and platelets counts were measured at admission. RESULTS: The incidence of heart rupture, acute heart failure, total adverse events, and death resulting from all events were significantly higher in patients ≥ 60 years than in younger patients, whereas the incidence of postoperative angina and reinfarction were similar between groups. Regarding blood counts, total white blood cells, neutrophils, lymphocytes, and platelets were lower in the older group than in the younger group. The platelet-to-lymphocyte ratio (PLR) was significantly higher in the older group. In receiver operating characteristic curve analysis, high PLR > 147 predicted adverse events (specificity 72% and sensitivity 63%). In multiple logistic regression analysis, age, hypertension, and PLR were identified as independent predictors of adverse events. CONCLUSIONS: The in-hospital outcomes of elderly patients with acute myocardial infarction were poor. PLR was an independent risk factor for in-hospital adverse events, which suggested that strong inflammation and prothrombotic status may contribute to the poor prognoses of elderly patients.

lncRNA 430945 promotes the proliferation and migration of vascular smooth muscle cells via the ROR2/RhoA signaling pathway in atherosclerosis.

The proliferation and migration of vascular smooth muscle cells (VSMCs) are major cellular events in hypertension­induced vascular remodeling, which is closely involved in the progression of atherosclerosis (AS). Although long non­coding RNAs (lncRNAs) are gaining recognition as novel regulators of VSMCs, their functioning and role in AS remain to be elucidated. In the present study, the role of lncRNA ENST00000430945 (lncRNA 430945) in AS was investigated. VSMCs transfected with a small interfering RNA (siRNA; si­430945) and a negative control (si­NC) were used. Cell Counting Kit­8, wound­healing and Transwell migration arrays were performed to determine whether lncRNA 430945 influenced VSMC proliferation and migration. Furthermore, the study examined whether a correlation exists between lncRNA 430945 and the receptor tyrosine kinase­like orphan receptor 2 (ROR2) signaling pathway. It was found that the expression of lncRNA 430945 was high in human AS tissues, which in turn promoted angiotensin II (AngII)­induced VSMC proliferation. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and western blot analyses showed that lncRNA 430945 mediated the AngII­induced upregulation of ROR2. In addition, the microarray and RT­qPCR results showed that the expression of lncRNA 430945 was increased considerably in AS tissues. The downregulation of lncRNA 430945 significantly suppressed AngII­induced VSMC proliferation and migration. In addition, ROR2 levels in VSMCs transfected with si­430945 were markedly lower than those cells transfected with si­NC. Additionally, western blotting showed that lncRNA 430945 activated the signaling pathways associated with ROR2 and Ras homolog gene family member A (RhoA). The upregulation of lncRNA 430945 in AS promoted the proliferation and migration of VSMCs via activation of the ROR2/RhoA signaling pathway. Therefore, targeting ROR2 or RhoA may be a promising technique in developing therapeutic strategies for treating AS.

Hyperuricemia is associated with short-term outcomes in elderly patients with acute myocardial infarction.

BACKGROUND: Although a lot of studies have  shown serum uric acid (SUA) could be a marker of adverse prognosis in patients with acute myocardial infarction, the role of SUA as a risk factor for myocardial infarction is controversial. This study aimed to evaluate the association between hyperuricemia and short-term outcomes of elderly patients with acute ST-segment elevation myocardial infarction (STEMI). METHODS: Six hundred and seventy-three elderly patients (≥ 60 years) were divided into high-SUA-level group (group H: N = 168) and low-SUA-level group (group L: N = 505) according to the SUA levels on admission. The following primary end points were evaluated within 30 days of AMI. The adverse events included postoperative angina pectoris, heart failure (Killip class ≥ II), and death. The comparisons were made between two groups in clinical and angiographic characteristics. RESULTS: The incidences of postoperative angina pectoris, heart failure, and the total adverse cardiovascular events were significantly higher in group H than in group L. But the incidence of death was similar between groups. In group H, heart rate (HR), systolic and diastolic blood pressure, SUA, homocysteine (HCY), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and creatine kinase myocardial band (CKMB) peak were clearly higher compared with those in group L. The results of logistic regression showed that the incidence of 30-day adverse events was closely related to TG, HCY and SUA. CONCLUSIONS: An elevated SUA level may be related to the short-term outcomes and seems to be an independent predictor of 30-day cardiovascular events in elderly patients with STEMI.

Ideal cardiovascular health score and incident end-stage renal disease in a community-based longitudinal cohort study: the Kailuan Study.

OBJECTIVES: To investigate an association between ideal cardiovascular health metrics (CVH) and the risk of developing end-stage renal disease (ESRD). SETTING: Community of Kailuan in Tangshan/China. PARTICIPANTS: We examined in a community-based longitudinal cohort study 91 443 participants without history of stroke or myocardial infarction at baseline in 2006-2007, with a glomerular filtration rate (GFR) ≥15 mL/min at baseline, and who participated in at least 1 of 3 follow-up examinations in 2008-2009, 2010-2011 and 2012-2013. INTERVENTIONS: CVH was measured by 7 key health factors (smoking, body mass index, physical activity, healthy dietary score, total cholesterol blood concentration, blood pressure, fasting blood glucose) each of which ranged between 'ideal' (2) and 'poor' (0). With a maximal CVH score of 14, the study participants were divided into categories of <5, 5-9 and 10-14 points. PRIMARY AND SECONDARY OUTCOME MEASURES: CHV, incidence of ESRD. RESULTS: Incidence of ESRD ranged from 7.06‰ in the lowest CVH category to 2.34‰ in the highest CVH category. After adjusting for age, sex, educational level, income, alcohol consumption and GFR, the lowest CVH category as compared with the highest CVH category had a significantly higher risk of incident ESRD (adjusted HR 2.87; 95% CI 1.53 to 5.39). For every decrease in group number of the cum-CVH score, the risk of ESRD increased by 20% (HR 1.20; 95% CI 1.13 to 1.28). The effect was consistent across sex and all age groups. CONCLUSIONS: A low CVH score significantly increased the risk of incident ESRD. Risk factors for cardiovascular events may also be associated with an increased risk for kidney failure.

Screening and identification of microRNA involved in unstable angina using gene-chip analysis.

Increasing evidence has suggested that microRNA (miRNA) may play a role in the pathogenesis of cardiovascular disease, which has led to a greater understanding of the complex pathophysiological processes underlying unstable angina (UA). The present study aimed to investigate changes in the miRNA expression profiles of patients with UA using gene-chip analysis, in order to further elucidate the pathogenesis of UA. Total RNA was extracted and purified from plasma samples collected from patients with UA and healthy controls. The samples underwent microarray analysis using an Exiqon miRCURY LNA™ microRNA Array. Differentially expressed miRNAs were identified by volcano plot filtering, and were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, functional annotation of the differentially expressed miRNAs involved gene ontology analyses. Among the 212 miRNAs differentially expressed between the two groups, 82 were upregulated and 130 were downregulated. Notably, the results of the RT-qPCR were consistent with the gene-chip results. The miRNAs identified in the present study may be potential novel biomarkers for the prevention and early diagnosis of UA. Furthermore, the results of the present study suggested that UA occurs as a result of complex and dynamic processes regulated by numerous factors, including multiple miRNAs.

MicroRNA 28-5p regulates ATP-binding cassette transporter A1 via inhibiting extracellular signal-regulated kinase 2.

The biological function of the intronic microRNA-28 (miR-28) may be associated with the biological roles of its host gene, LIM domain lipoma­preferred partner (LPP). LPP has been reported to promote smooth muscle cell migration in arterial injury and atherosclerosis. However, the mechanism of miR­28 in atherosclerosis remains unclear. In the current study, the aim was to validate the inhibitory effect of miR­28­5p on extracellular signal­regulated kinase 2 (ERK2), to investigate its biological role in atherosclerosis and its association with cardiovascular disease. Western blotting and stem­loop reverse transcription­quantitative polymerase chain reaction combined with TaqMAN microRNA analysis was conducted. The current study demonstrated that miR­28­5p upregulated the expression of ATP­binding cassette transporter A1 (ABCA1) via the inhibition of ERK2 in HepG2 cells. In addition, increased levels of plasma miR­28­5p were positively correlated with the levels of high­density lipoprotein cholesterol in patients with unstable angina. This suggests that miR-28-5p participates in atherosclerosis via ERK2-mediated upregulation of the ABCA1 pathway.

Correlation Between Hyperhomocysteinemia and Outcomes of Patients With Acute Myocardial Infarction.

Overwhelming clinical and epidemiological studies have identified elevated plasma total homocysteine (Hcy) as new important risk factor for atherosclerotic vascular disease. But the relationship between outcome and hyperhomocysteinemia in patients with acute myocardial infarction (AMI) has been rarely reported. This study aimed to evaluate the association between hyperhomocysteinemia and short-term outcomes of patients with AMI. Eight hundred five patients were divided into high Hcy level group (group H: N = 457) and low Hcy level group (group L: N = 348) according to the plasma Hcy levels of 15 mmol/L. The comparisons were made between 2 groups in the following aspects: sex, hypertension, diabetes, hyperlipidemia, the time for symptom from onset to percutaneous coronary intervention, homoccyteine, creatine phosphokinase isoenzyme (creatine kinase myocardial band), and the incidence of 30-day adverse events. The incidences of heart failure, cardiac rupture, death, and the total adverse cardiovascular events were statistically significantly higher in group H than in group L. But the incidence of postoperative angina pectoris and reinfarction was similar between groups. The results of logistic regression showed that the incidence of 30-day adverse events was closely related to the age and the level of Hcy. An elevated plasma total Hcy level in patients with AMI experienced pemutaneous coronary intervention may be related to the short-term outcomes. An elevated high plasma Hcy level also seems to be an independent predictor of 30-day cardiovascular events in patients with AMI.

Drug-Induced Acute Liver Injury Within 12 Hours After Fluvastatin Therapy.

Although statins are generally well-tolerated drugs, recent cases of drug-induced liver injury associated with their use have been reported. A 52-year-old Chinese man reported with liver damage, which appeared 12 hours after beginning treatment with fluvastatin. Patient presented with complaints of increasing nausea, anorexia, and upper abdominal pain. His laboratory values showed elevated creatine kinase and transaminases. Testing for autoantibodies was also negative. The liver biochemistries eventually normalized within 3 weeks of stopping the fluvastatin. Therefore, when prescribing statins, the possibility of hepatic damage should be taken into account.

miR-146a-5p Antagonized AGEs- and P.g-LPS-Induced ABCA1 and ABCG1 Dysregulation in Macrophages via IRAK-1 Downregulation.

The miR-146-mediated IL-1 receptor-associated kinase 1 (IRAK-1) feedback circuit has been shown to inhibit inflammatory response in macrophages against lipopolysaccharide (LPS). The aim of this study is to compare the antagonized effects of miR-146a-5p on Porphyromonas gingivalis (P.g) lipolysaccharide (LPS)- and advanced glycation end products (AGEs)-triggered ABCA1 and ABCG1 dysregulation and explore the underlying mechanism. THP-1-derived macrophages transfected with miRNA mimics or not were treated with P.g LPS or AGE-BSA, respectively. The mechanism of endotoxin tolerance was mimicked. miR-146a-5p levels and protein levels of IRAK-1, LXRα/ß, ABCA1, and ABCG1 were detected by stem-loop reverse transcription followed by TaqMan PCR analysis and Western blotting. Our results showed that miR-146a-5p levels were significantly increased in macrophages after 24 h of stimulation with high dose of P.g LPS or AGE-BSA. Macrophages transfected with miR-146a-5p mimics attenuated the dysregulation of ABCA1/G1 induced by P.g LPS and AGEs through IRAK-1 downregulation. In low-dose LPS-tolerized cells, elevated miR-146a-5p antagonized the increase of ABCA1, ABCG1, and IRAK-1. However, low-dose AGE-BSA did not increase miR-146a-5p levels. In conclusion, the model of endotoxin tolerance is suitable for the antagonistic effects on the dysregulation of ABCA1/G1 induced by high dose of P.g LPS. Conversely, low-dose AGEs did not induce the model of P.g LPS-mediated tolerance.

miR-28-5p Involved in LXR-ABCA1 Pathway is Increased in the Plasma of Unstable Angina Patients.

BACKGROUND: Previous studies confirmed that the intronic miRNAs participated in regulating host gene-primed biological processes. The coordinated roles of miR-28 with its host gene, LIM domain lipoma-preferred partner (LPP), remain unknown in atherosclerosis. METHODS: In this study, we determined to assess circulating levels of miR-28-5p in unstable angina patients, compared with age- and sex- matched control subjects by quantitative PCR. Furthermore, we attempted to explore whether miR-28-5p could influence the expression of ATP-binding cassette transporter A1 (ABCA1) and liver X receptor (LXR), major mediators of high density lipoprotein (HDL) synthesis and transportation in hepatic cells and macrophages. RESULTS: It was found that plasma levels of miR-28-5p were significantly increased in unstable angina patients with or without type 2 diabetes mellitus. Notably, miR-28-5p upregulated ABCA1 expression at transcription and translation levels, strongly correlated with translational activation of LXRα in HepG2 and THP-1-derived macrophages. CONCLUSIONS: Our findings suggest that circulating miR-28-5p, involved in LXRα-ABCA1 pathway, may be a potential biomarker for diagnosis and prognosis of unstable angina.

Association of two well-defined polymorphisms in leptin and leptin receptor genes with hypertension and circulating leptin: a meta-analysis.

BACKGROUND AND AIMS: The genes encoding adipose-derived hormone leptin and its receptor (LEPR) are increasingly deemed as hypertension-susceptibility genes. In this meta-analysis, we summarized the association of the II/I polymorphism in leptin gene and Gln223Arg polymorphism in LEPR gene with hypertension and circulating leptin. METHODS: PubMed and Embase were systematically searched. Data extraction and study quality were assessed in duplicate. Statistical analyses were carried out with the STATA software (v. 11.2). RESULTS: A total of 11 articles written in English were eligible. Overall analysis identified a significant association between II/I polymorphism I allele and increased risk of hypertension under allelic (odds ratio; 95% confidence interval; P: 1.48; 1.06-2.08; 0.022) and homozygous genotypic (2.27; 1.20-4.29; 0.012) models. The magnitude of the association for II/I polymorphism I allele with hypertension was substantiated in Asians and for essential hypertension under both genetic models. Overall and subgroup analyses failed to reveal any significance for the association between the Gln223Arg polymorphism and hypertension risk. Carriers of Gln223Arg polymorphism Gln/Gln genotype had significantly higher circulating leptin than the Arg/Arg genotype carriers (weighted mean difference; 95% confidence interval; P: 1.61 ng/mL; 0.02-3.20; 0.047), and this significance persisted in essential hypertension subgroup (1.69 ng/mL; 0.02-3.35; 0.047). There were low probabilities of publication bias for the above comparisons. CONCLUSIONS: Our findings support the contributory role of the II/I polymorphism in leptin gene in the pathogenesis of hypertension, and this role was more evident in Asians and for essential hypertension.

Effects of Shenshao Decoction on the inflammatory response in the aorta of a rat atherosclerotic model.

OBJECTIVE: To investigate the effect of Shenshao Decoction on the inflammatory status: in the aorta in a rat model of atherosclerosis. METHODS: Forty Sprague-Dawley rats were randomly divided into: five groups, 8 rats in each group: control untreated group, atherosclerosis group, atherosclerosis with Shenshao Decoction (low dose) group, atherosclerosis with Shenshao Decoction (high dose) group, atherosclerosis with simvastatin group. To stimulate atherosclerosis, the rats were fed vitamin D3 and a high-cholesterol diet. Four weeks later, treatments were maintained for eight weeks. Morphology changes were investigated by hematoxylin and eosin staining. Serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) were obtained by enzymatic assays with use of an automated biochemical analyzer. The expression of malondialdehyde (MDA), glutathione peroxidase (GSH-PX) were detected by enzyme-enzymelinked immunosorbent assay. The expression levels of interleukin (IL)-1ß, IL-17A, and IL-23 were detected by linked immunoblotting. RESULTS: Shenshao Decoction treatment decreased TC, TG, LDL-C and MDA and increased: GSH-PX levels (P<0.01). Compared with the control group, IL-1ß, IL-17A, and IL-23 were lower in the high and

Analysis of factors related to short-term prognosis in patients undergoing percutaneous coronary intervention for acute myocardial infarction.

The present study aimed to investigate the factors related to short-term prognosis in patients undergoing direct percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI). A total of 805 patients were included and divided into a control group and an adverse cardiovascular events group based on the prognosis, to compare risk factors and coronary angiographic characteristics in the two groups. In the adverse events group, the ages, admission blood glucose, uric acid (UA), homocysteine (HCY), creatine kinase (CK) and peak creatine kinase-MB (CKMB) isozyme levels were clearly higher compared with those in the control group, while the levels of total cholesterol (TC), triglycerides (TGs) and low-density lipoprotein (LDL) were lower compared with those in the control group. The incidence of hypertension in females in the adverse events group was markedly higher compared with that in the control group, while the diabetes rate was lower compared with that in the control group. Logistic regression analysis revealed that age, gender, hypertension, diabetes and admission blood glucose, HCY, TC and UA levels were independent risk factors of short-term prognosis in patients undergoing emergency PCI. The majority of the patients in the adverse events group were elderly females with hypertension, a large area of myocardial infarction and increased admission blood glucose, UA and HCY levels, as well as a low diabetes rate and decreased levels of acute-phase TC and LDL.

Rho-associated coiled kinase inhibitor Y-27632 promotes neuronal-like differentiation of adult human adipose tissue-derived stem cells.

BACKGROUND: Y-27632 is a specific inhibitor of Rho-associated coiled kinase (ROCK) and has been shown to promote the survival and induce the differentiation of a variety of cells types. However, the effects of Y-27632 on adult human adipose tissue-derived stem cells (ADSCs) are unclear. This study aimed to investigate the effects of Y-27632 on the neuronal-like differentiation of ADSCs. METHODS: ADSCs were isolated from women undergoing plastic surgery and cultured. ADSCs were treated with different doses of Y-27632 and observed morphological changes under microscope. The expression of nestin, neuron specific enolase (NSE) and microtubule-associated protein-2 (MAP-2) in ADSCs treated with Y-27632 was detected by immunocytochemistry and Western blotting analysis. RESULTS: Y-27632 had the potency to induce neuronal-like differentiation in ADSCs in a dose-dependent manner. Moreover, the differentiation induced by Y-27632 was recovered upon drug withdraw. ADSCs treated with Y-27632 expressed neuronal markers such as NSE, MAP-2 and nestin while untreated ADSCs did not express these markers. CONCLUSION: Selective ROCK inhibitor Y-27632 could potentiate the neuronal-like differentiation of ADSCs, suggesting that Y-27632 could be utilized to induce the differentiation of ADSCs to neurons and facilitate the clinical application of ADSCs in tissue engineering.

The appearance of pulmonary mucormycosis on FDG PET/CT.

Pulmonary mucormycosis is a life-threatening opportunistic mycosis that is difficult to diagnose early. We report the case of a 56-year-old woman who complained of intermittent fever in the afternoon and productive cough and pain on the right side of the chest. Her clinical condition deteriorated despite antibiotherapy. FDG PET/CT showed a heterogeneous soft tissue mass at the lower part of the right lung with obvious FDG uptake in the peripheral part of the mass. Mucormycosis was proven by histopathology and fungal culture from the transbronchial lung biopsy materials.

Endovascular treatment of intracranial aneurysms using coil embolization plus an Enterprise stent.

BACKGROUND: Several difficulties can arise from wide-neck cerebral aneurysms when treated with endovascular embolization. We aimed to investigate the effect of endovascular treatment of intracranial aneurysms using coil embolization plus an Enterprise stent. METHODS: Forty patients were treated with coil embolization plus an Enterprise stent between December 2008 and June 2010. RESULTS: The mortality of patients was 0. All stents were successfully implanted without any surgery-related complication. CONCLUSION: The Enterprise stent has some advantages to be selected.