Serum ferritin and neutrophil-to-lymphocyte ratio predict all-cause mortality in patients receiving maintenance hemodialysis: a prospective study.

Introduction: Maintenance hemodialysis is an effective treatment for end-stage renal disease patients. A critical factor contributing to the deterioration and death of maintenance hemodialysis patients is inflammation. Therefore, we focused on two inflammatory markers, serum ferritin and neutrophil-to-lymphocyte ratio, to speculate whether they could predict the prognosis of maintenance hemodialysis patients. Patients and methods: We followed 168 patients with maintenance hemodialysis from July 2019 to July 2022 with the endpoint of all-cause death or follow-up completion. Receiver operating characteristic curves were plotted to assess the values of serum ferritin, neutrophil-to-lymphocyte ratio and serum ferritin combined with neutrophil-to-lymphocyte ratio to predict the outcomes of maintenance hemodialysis patients. Kaplan-Meier survival curves were constructed to compare survival rates over time. Results: Receiver operating characteristic curves demonstrated that the best cut-off value of serum ferritin for predicting the prognosis of maintenance hemodialysis patients was 346.05 µg/L, and that of neutrophil-to-lymphocyte ratio was 3.225. Furthermore, a combination of both had a more excellent predicting value than either index (p < 0.05). Kaplan-Meier survival curve analyses revealed that low serum ferritin levels and low neutrophil-to-lymphocyte ratio had a higher probability of survival than high ferritin levels and high neutrophil-to-lymphocyte ratio, separately. Conclusion: Elevated serum ferritin and neutrophil-to-lymphocyte ratio are closely related to all-cause mortality among maintenance hemodialysis patients, for which they may be predictors of all-cause mortality. Additionally, the combination of the two has a much higher predictor value for the prognosis of maintenance hemodialysis patients.

Integrated analysis and validation of ferroptosis-related genes and immune infiltration in acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) is indeed a significant cause of mortality and morbidity in individuals with coronary heart disease. Ferroptosis, an iron-dependent cell death, is characterized by the accumulation of intracellular lipid peroxides, which is implicated in cardiomyocyte injury. This study aims to identify biomarkers that are indicative of ferroptosis in the context of AMI, and to examine their potential roles in immune infiltration. METHODS: Firstly, the GSE59867 dataset was used to identify differentially expressed ferroptosis-related genes (DE-FRGs) in AMI. We then performed gene ontology (GO) and functional enrichment analysis on these DE-FRGs. Secondly, we analyzed the GSE76591 dataset and used bioinformatic methods to build ceRNA networks. Thirdly, we identified hub genes in protein-protein interaction (PPI) network. After obtaining the key DE-FRGs through the junction of hub genes with ceRNA and least absolute shrinkage and selection operator (LASSO). ImmucellAI was applied to estimate the immune cell infiltration in each sample and examine the relationship between key DE-FRGs and 24 immunocyte subsets. The diagnostic performance of these genes was further evaluated using the receiver operating characteristic (ROC) curve analysis. Ultimately, we identified an immune-related ceRNA regulatory axis linked to ferroptosis in AMI. RESULTS: Among 56 DE-FRGs identified in AMI, 41 of them were integrated into the construction of competitive endogenous RNA (ceRNA) networks. TLR4 and PIK3CA were identified as key DE-FRGs and PIK3CA was confirmed as a diagnostic biomarker for AMI. Moreover, CD4_native cells, nTreg cells, Th2 cells, Th17 cells, central-memory cells, effector-memory cells, and CD8_T cells had higher infiltrates in AMI samples compared to control samples. In contrast, exhausted cells, iTreg cells, and Tfh cells had lower infiltrates in AMI samples. Spearman analysis confirmed the correlation between 24 immune cells and PIK3CA/TLR4. Ultimately, we constructed an immune-related regulatory axis involving XIST and OIP5-AS1/miR-216a/PIK3CA. CONCLUSION: Our comprehensive analysis has identified PIK3CA as a robust and promising biomarker for this condition. Moreover, we have also identified an immune-related regulatory axis involving XIST and OIP5-AS1/miR-216a/PIK3CA, which may play a key role in regulating ferroptosis during AMI progression.

Noncoding RNAs regulating ferroptosis in cardiovascular diseases: novel roles and therapeutic strategies.

The morbidity and mortality rates of cardiovascular diseases (CVDs) are increasing; thus, they impose substantial health and economic burdens worldwide, and effective interventions are needed for immediate resolution of this issue. Recent studies have suggested that noncoding RNAs (ncRNAs) play critical roles in the occurrence and development of CVDs and are potential therapeutic targets and novel biomarkers for these diseases. Newly discovered modes of cell death, including necroptosis, pyroptosis, apoptosis, autophagy-dependent cell death and ferroptosis, also play key roles in CVD progression. However, ferroptosis, which differs from the other aforementioned forms of regulated cell death in terms of cell morphology, biochemistry and inhereditability, is a unique iron-dependent mode of nonapoptotic cell death induced by abnormal iron metabolism and excessive accumulation of iron-dependent lipid peroxides and reactive oxygen species (ROS). Increasing evidence has confirmed that ncRNA-mediated ferroptosis is involved in regulating tissue homeostasis and CVD-related pathophysiological conditions, such as cardiac ischemia/reperfusion (I/R) injury, myocardial infarction (MI), atrial fibrillation (AF), cardiomyopathy and heart failure (HF). In this review, we summarize the underlying mechanism of ferroptosis, discuss the pathophysiological effects of ncRNA-mediated ferroptosis in CVDs and provide ideas for effective therapeutic strategies.

Interpretable prediction of 3-year all-cause mortality in patients with chronic heart failure based on machine learning.

BACKGROUND: The goal of this study was to assess the effectiveness of machine learning models and create an interpretable machine learning model that adequately explained 3-year all-cause mortality in patients with chronic heart failure. METHODS: The data in this paper were selected from patients with chronic heart failure who were hospitalized at the First Affiliated Hospital of Kunming Medical University, from 2017 to 2019 with cardiac function class III-IV. The dataset was explored using six different machine learning models, including logistic regression, naive Bayes, random forest classifier, extreme gradient boost, K-nearest neighbor, and decision tree. Finally, interpretable methods based on machine learning, such as SHAP value, permutation importance, and partial dependence plots, were used to estimate the 3-year all-cause mortality risk and produce individual interpretations of the model's conclusions. RESULT: In this paper, random forest was identified as the optimal aools lgorithm for this dataset. We also incorporated relevant machine learning interpretable tand techniques to improve disease prognosis, including permutation importance, PDP plots and SHAP values for analysis. From this study, we can see that the number of hospitalizations, age, glomerular filtration rate, BNP, NYHA cardiac function classification, lymphocyte absolute value, serum albumin, hemoglobin, total cholesterol, pulmonary artery systolic pressure and so on were important for providing an optimal risk assessment and were important predictive factors of chronic heart failure. CONCLUSION: The machine learning-based cardiovascular risk models could be used to accurately assess and stratify the 3-year risk of all-cause mortality among CHF patients. Machine learning in combination with permutation importance, PDP plots, and the SHAP value could offer a clear explanation of individual risk prediction and give doctors an intuitive knowledge of the functions of important model components.

Advanced lung cancer inflammation index combined with geriatric nutritional risk index predict all-cause mortality in heart failure patients.

BACKGROUND: This study was undertaken to explore the predictive value of the advanced lung cancer inflammation index (ALI) combined with the geriatric nutritional risk index (GNRI) for all-cause mortality in patients with heart failure (HF). METHODS AND RESULTS: We enrolled 1123 patients with HF admitted to our cardiology department from January 2017 to October 2021. Patients were divided into four groups, according to the median ALI and GNRI. From the analysis of the relationship between the ALI and GNRI, we concluded that there was a mild positive linear correlation (r = 0.348, p < 0.001) and no interaction (p = 0.140) between the ALI and GNRI. Kaplan‒Meier analysis showed that the cumulative incidence of all-cause mortality in patients with HF was highest in Group 1 (log-rank χ2 126.244, p < 0.001). Multivariate Cox proportional hazards analysis revealed that ALI and GNRI were independent predictors of all-cause mortality in HF patients (ALI: HR 0.407, 95% CI 0.296-0.560, p < 0.001; GNRI: HR 0.967, 95% CI 0.954-0.980, p < 0.001). The area under the curve (AUC) for ALI combined with GNRI was 0.711 (p < 0.001), according to the time-dependent ROC curve. CONCLUSION: ALI and GNRI were independent predictors of all-cause mortality in HF patients. Patients with HF had the highest risk of all-cause mortality when the ALI was < 24.60 and the GNRI was < 94.41. ALI combined with the GNRI has good predictive value for the prognosis of HF patients.

Luteolin inhibits GPVI-mediated platelet activation, oxidative stress, and thrombosis.

Introduction: Luteolin inhibits platelet activation and thrombus formation, but the mechanisms are unclear. This study investigated the effects of luteolin on GPVI-mediated platelet activation in vitro and explored the effect of luteolin on thrombosis, coagulation, and platelet production in vivo. Methods: Washed human platelets were used for aggregation, membrane protein expression, ATP, Ca2+, and LDH release, platelet adhesion/spreading, and clot retraction experiments. Washed human platelets were used to detect collagen and convulxin-induced reactive oxygen species production and endogenous antioxidant effects. C57BL/6 male mice were used for ferric chloride-induced mesenteric thrombosis, collagen-epinephrine induced acute pulmonary embolism, tail bleeding, coagulation function, and luteolin toxicity experiments. The interaction between luteolin and GPVI was analyzed using solid phase binding assay and surface plasmon resonance (SPR). Results: Luteolin inhibited collagen- and convulxin-mediated platelet aggregation, adhesion, and release. Luteolin inhibited collagen- and convulxin-induced platelet ROS production and increased platelet endogenous antioxidant capacity. Luteolin reduced convulxin-induced activation of ITAM and MAPK signaling molecules. Molecular docking simulation showed that luteolin forms hydrogen bonds with GPVI. The solid phase binding assay showed that luteolin inhibited the interaction between collagen and GPVI. Surface plasmon resonance showed that luteolin bonded GPVI. Luteolin inhibited integrin αIIbß3-mediated platelet activation. Luteolin inhibited mesenteric artery thrombosis and collagen- adrenergic-induced pulmonary thrombosis in mice. Luteolin decreased oxidative stress in vivo. Luteolin did not affect coagulation, hemostasis, or platelet production in mice. Discussion: Luteolin may be an effective and safe antiplatelet agent target for GPVI. A new mechanism (decreased oxidative stress) for the anti-platelet activity of luteolin has been identified.

Prognostic Significance of Serum Chloride Level Reduction in Patients with Chronic Heart Failure with Different Ejection Fractions.

Little is known regarding the prognostic value of serum chloride in patients with chronic heart failure (CHF) with different ejection fractions. We sought to determine the postdischarge outcomes associated with lower serum chloride between different CHF types.We reviewed the medical records of 1221 consecutive patients with CHF admitted to the First Affiliated Hospital of Kunming Medical University from January 2017 to October 2021. After excluding patients with in-hospital death, missing follow-up data, missing serum chloride level data, or chronic dialysis therapy, 791 patients were included. Of these patients, 343 had heart failure with reduced ejection fraction (HFrEF; i.e., left ventricular ejection fraction (LVEF) < 40%), and 448 had heart failure with preserved ejection fraction (HFpEF) or heart failure with median ejection fraction (HFmrEF; HFpEF plus HFmrEF; i.e., LVEF ≥40%). Over a median follow-up of 750 days, 344 patients (43.5%) had all-cause mortality. In the univariate analysis, serum sodium and chloride were strongly associated with mortality in both HF subgroups (P < 0.0001). A multivariable model including both serum sodium and chloride showed the highly significant association between serum chloride and survival (P < 0.0001), whereas the association between serum sodium and mortality was not reported (HFpEF plus HFmrEF, hazard ratio (HR) 0.975, 95% confidence interval [CI] 0.942-1.010, P = 0.158; HFrEF, HR 1.007, 95% CI 0.966-1.051, P = 0.734). Kaplan-Meier survival curve analysis revealed a significant difference in mortality risk with decreasing chloride levels in all patients with CHF. The optimal cutoff value of chloride in predicting all-cause mortality was 102.95 mmol/L with area under the curve value of 0.76 [HR 0.760, 95% CI 0.727-0.793, P < 0.0001], sensitivity of 60.2%, and specificity of 78.3%.Lower serum chloride is an independent predictor of death in CHF, regardless of heart failure subtype.

Promising roles of non-exosomal and exosomal non-coding RNAs in the regulatory mechanism and as diagnostic biomarkers in myocardial infarction. / 非外泌体/å¤–æ³Œä½“éžç¼–ç RNAsåœ¨å‚ä¸Žå¿ƒè‚Œæ¢—æ­»è°ƒèŠ‚åŠä½œä¸ºè¯Šæ–­æ€§ç”Ÿç‰©æ ‡å¿—ç‰©æ–¹é¢çš„ä½œç”¨.

Non-exosomal non-coding RNAs (non-exo-ncRNAs) and exosomal ncRNAs (exo-ncRNAs) have been associated with the pathological development of myocardial infarction (MI). Accordingly, this analytical review provides an overview of current MI studies on the role of plasma non-exo/exo-ncRNAs. We summarize the features and crucial roles of ncRNAs and reveal their novel biological correlations via bioinformatics analysis. The following contributions are made: (1) we comprehensively describe the expression profile, competing endogenous RNA (ceRNA) network, and "pre-necrotic" biomarkers of non-exo/exo-ncRNAs for MI; (2) functional enrichment analysis indicates that the target genes of ncRNAs are enriched in the regulation of apoptotic signaling pathway and cellular response to chemical stress, etc.; (3) we propose an updated and comprehensive view on the mechanisms, pathophysiology, and biomarker roles of non-exo/exo-ncRNAs in MI, thereby providing a theoretical basis for the clinical management of MI.

New developments in non-exosomal and exosomal ncRNAs in coronary artery disease.

Aim & methods: Non-exosomal and exosomal ncRNAs have been reported to be involved in the regulation of coronary artery disease (CAD). Therefore, to explore the biological effects of non-exosomal/exosomal ncRNAs in CAD, the authors searched for studies published in the last 3 years on these ncRNAs in CAD and summarized their functions and mechanisms. Results: The authors summarized 120 non-exosomal ncRNAs capable of regulating CAD progression. In clinical studies, 47 non-exosomal and nine exosomal ncRNAs were able to serve as biomarkers for the diagnosis of CAD. Conclusion: Non-exosomal/exosomal ncRNAs are not only able to serve as biomarkers for CAD diagnosis but can also regulate CAD progression through ceRNA mechanisms and are a potential target for early clinical intervention in CAD.

ncRNAs are increasingly found to play regulatory roles in coronary artery disease (CAD), and transcriptome studies offer greater advantages for controlling CAD at its source. Therefore, the authors conducted an accurate search and summary of studies on CAD and ncRNAs published in the past 3 years to analyze the main pathological mechanisms in CAD progression, aiming to provide a research basis for clinical treatment of CAD.

Identification of immune-related hub genes and miRNA-mRNA pairs involved in immune infiltration in human septic cardiomyopathy by bioinformatics analysis.

Abstract: Septic cardiomyopathy (SCM) is a serious complication caused by sepsis that will further exacerbate the patient's prognosis. However, immune-related genes (IRGs) and their molecular mechanism during septic cardiomyopathy are largely unknown. Therefore, our study aims to explore the immune-related hub genes (IRHGs) and immune-related miRNA-mRNA pairs with potential biological regulation in SCM by means of bioinformatics analysis and experimental validation. Method: Firstly, screen differentially expressed mRNAs (DE-mRNAs) from the dataset GSE79962, and construct a PPI network of DE-mRNAs. Secondly, the hub genes of SCM were identified from the PPI network and the hub genes were overlapped with immune cell marker genes (ICMGs) to further obtain IRHGs in SCM. In addition, receiver operating characteristic (ROC) curve analysis was also performed in this process to determine the disease diagnostic capability of IRHGs. Finally, the crucial miRNA-IRHG regulatory network of IRHGs was predicted and constructed by bioinformatic methods. Real-time quantitative reverse transcription-PCR (qRT-PCR) and dataset GSE72380 were used to validate the expression of the key miRNA-IRHG axis. Result: The results of immune infiltration showed that neutrophils, Th17 cells, Tfh cells, and central memory cells in SCM had more infiltration than the control group; A total of 2 IRHGs were obtained by crossing the hub gene with the ICMGs, and the IRHGs were validated by dataset and qRT-PCR. Ultimately, we obtained the IRHG in SCM: THBS1. The ROC curve results of THBS1 showed that the area under the curve (AUC) was 0.909. Finally, the miR-222-3p/THBS1 axis regulatory network was constructed. Conclusion: In summary, we propose that THBS1 may be a key IRHG, and can serve as a biomarker for the diagnosis of SCM; in addition, the immune-related regulatory network miR-222-3p/THBS1 may be involved in the regulation of the pathogenesis of SCM and may serve as a promising candidate for SCM therapy.

Integrated bioinformatics analysis for novel miRNAs markers and ceRNA network in diabetic retinopathy.

In order to seek a more outstanding diagnosis and treatment of diabetic retinopathy (DR), we predicted the miRNA biomarkers of DR and explored the pathological mechanism of DR through bioinformatics analysis. Method: Based on public omics data and databases, we investigated ncRNA (non-coding RNA) functions based on the ceRNA hypothesis. Result: Among differentially expressed miRNAs (DE-miRNAs), hsa-miR-1179, -4797-3p and -665 may be diagnosis biomarkers of DR. Functional enrichment analysis revealed differentially expressed mRNAs (DE-mRNAs) enriched in mitochondrial transport, cellular respiration and energy derivation. 18 tissue/organ-specific expressed genes, 10 hub genes and gene cluster modules were identified. The ceRNA networks lncRNA FBXL19-AS1/miR-378f/MRPL39 and lncRNA UBL7-AS1/miR-378f/MRPL39 might be potential RNA regulatory pathways in DR. Conclusion: Differentially expressed hsa-miR-1179, -4797-3p and -665 can be used as powerful markers for DR diagnosis, and the ceRNA network: lncRNA FBXL19-AS1/UBL7-AS1-miR-378f-MRPL39 may represent an important regulatory role in DR progression.

Effect of Evodiamine on Collagen-Induced Platelet Activation and Thrombosis.

Evodia rutaecarpa has multiple pharmacological effects and is widely used in the prevention and treatment of migraine, diabetes, cardiovascular disease, cancer, and other chronic diseases; however, the pharmacological effects of its active compound evodiamine (Evo) have not been thoroughly investigated. The purpose of this study was to investigate the effects of Evo on antiplatelet activation and thrombosis. We discovered that Evo effectively inhibited collagen-induced platelet activation but had no effect on platelet aggregation caused by activators such as thrombin, ADP, and U46619. Second, we found that Evo effectively inhibited the release of platelet granules induced by collagen. Finally, evodiamine inhibits the transduction of the SFKs/Syk/Akt/PLCγ2 activation pathway in platelets. According to in vivo studies, Evo significantly prolonged the mesenteric thromboembolism induced by ferric chloride and had no discernible effect on the coagulation function of mice. In conclusion, the antiplatelet and thrombotic effects of Evo discovered in this study provide an experimental basis for the investigation of the pharmacological mechanisms of Evo and the development of antiplatelet drugs.

A negative feedback loop of H19/miR-675/EGR1 is involved in diabetic nephropathy by downregulating the expression of the vitamin D receptor.

AIM: We aimed to explore the regulatory relationship among the long noncoding RNA H19, micorRNA-675 (miR-675), the vitamin D (VD) receptor (VDR), and the early growth response protein 1 (EGR1) in the pathogenesis of diabetic nephropathy (DN) among patients with diabetes mellitus (DM). METHODS: Expression levels of H19, miR-675, VDR, and EGR in patients or CIHP-1/HEK 293 cells were measured via quantitative reverse-transcription polymerase chain reaction and western blot analysis. Computational analysis and luciferase assays were performed to determine EGR1 as a target gene of miR-675. RESULTS: The relative expression of miR-675 was higher in the presence of H19, whereas the expression of both VDR and EGR1 messenger RNA was decreased in the presence of H19 or miR-675. However, relative expression of H19 and miR-675 was increased, whereas VDR expression was suppressed upon the treatment of 1,25-dihydroxyvitamin D3 or EGR1. VDR was identified as a target gene of miR-675. The H19 promoter and EGR1 increased the luciferase activity of cells transfected with wild-type VDR. Compared with DM patients free of DN, the levels of H19 and miR-675 were increased in the DN(+) group, whereas the levels of VDR and EGR1 were decreased. CONCLUSION: In summary, the above results indicate the presence of a negative feedback loop in the pathological mechanism of DN, where H19 downregulates the expression of VDR by upregulating the expression of miR-675, whereas reduced VDR expression subsequently reduced the expression of EGR1. Moreover, reduced EGR1 expression inhibits H19 expression, thus forming a negative feedback loop required to maintain the homeostasis of VDR and to reduce the incidence of DN.

p21 protects cardiomyocytes against ischemia-reperfusion injury by inhibiting oxidative stress.

Ischemic heart disease is a major health threat, resulting in a large number of mortalities annually worldwide. Oxidative stress is one of the main causes of cell death during ischemia­reperfusion (IR) injury. Cyclin dependent kinase inhibitor 1A (known as p21) is important in protecting tissues against IR injury, however the mechanism remains unknown. In the present study, oxygen­glucose deprivation and subsequent reoxygenation (OGD/R) in H9c2 heart­derived myocytes was used as a model to study myocardial IR injury in vitro. mRNA and protein expression levels were determined by reverse transcription­quantitative polymerase chain reaction and western blotting, respectively. The levels of reactive oxygen species were measured using the fluorescence dye 2',7'­dichlorodihydrofluorescein diacetate. The present data demonstrated that p21 expression was upregulated by tumor protein p53 (p53) in H9c2 cells exposed to OGD/R. p21 protected H9c2 cells against OGD/R­induced oxidative stress. In addition, p21 mediated upregulation of NF­E2­related factor­2 (Nrf2), a regulator of antioxidant responses, which in turn suppressed cell death in H9c2 cells subjected to OGD/R. Thus, activation of the p53/p21/Nrf2 signaling pathway may be an important adaptive response that limits oxidative injury during IR.

Effect of cardiac shock wave therapy on the microvolt T wave alternans of patients with coronary artery disease.

OBJECTIVE: The aim of this study was to evaluate the effect of cardiac shock wave therapy (CSWT) on microvolt T wave alternans (MTWA) in patients with coronary artery disease (CAD). METHODS: 87 patients with old myocardial infarction (OMI) were enrolled in this study. Sixty-two patients were randomized into the CSWT group, 32 patients into the regular treatment group (Group A) according to different shock wave procedure, and 30 into the expanding scope treatment group (Group B), and 25 patients were randomized into the control group (Group C). But the shock wave (SW) energy was only applied to the patients in the CSWT group and not to the patients in the control group. Three months was a treatment course, thus patients received a total of 9 CSWT treatment sessions. RESULTS: Technetium-99m sestamibi myocardial perfusion, fluorine-18 fluorodeoxyglucose myocardial metabolism single-photon emission computed tomography (SPECT) were performed to identify segments of myocardial ischemia, myocardial viability, and microvolt T wave alternans (MTWA) before and after CSWT. After CSWT, the rehospitalization rates of CSWT group were lower than control group (P<0.05). The myocardial ischemic segments, metabolism abnormal segments, total radioactive score of perfusion imaging and metabolism imaging, MTWA, and MTWA/HR in CSWT group were reduced significantly (P<0.05). And the heart rate of maximum MTWA, exercise time were increased significantly (P<0.05). All of the parameters in the control group did not change significantly even worsen after the treatment (P>0.05). CONCLUSIONS: CSWT can reduce the MTWA value, improve the heart chronotropic function and increase the threshold of frequency which causes MTWA.

Exendin-4 regulates redox homeostasis in rats fed with high-fat diet.

Non-alcoholic fatty liver disease (NAFLD) is associated with increased plasma homocysteine level, which is caused by down-regulation of hepatic cystathionine beta-synthase (CBS) activity. CBS catalyzes the first step in the transsulfuration of homocysteine to cysteine, which contributes ∼50% of the cysteine required for hepatic biosynthesis of glutathione (GSH), the most abundant antioxidant in cells. As the glucagon-like peptide-1 (GLP-1) receptor agonists (e.g. exendin-4) effectively reverse hepatic steatosis, the effect of exendin-4 on both homocysteine and redox status was investigated in the livers of rats fed with high-fat diet (HFD). It was found that HFD down-regulated CBS protein expression, which was probably due to induction of rno-miR-376c expression in the liver. The level of GSH was markedly reduced, whereas the level of malonydialdehyde, an indicator of lipid peroxidation, was significantly increased in the livers of rats fed with HFD. Exendin-4 treatment increased hepatic CBS protein and GSH levels, and reduced malonydialdehyde level in hyperlipidemic rats. Our findings suggest that GLP-1 receptor agonists have beneficial effects on redox homeostasis in NAFLD.

Cardiac resynchronization therapy (CRT) with right ventricular sense triggered left ventricular pacing benefits for the hemodynamics compared with standard CRT for chronic congestive heart failure: A cross-over study.

BACKGROUND: The aim of this study was to investigate the effect of cardiac resynchronization therapy (CRT) with right ventricular (RV) sense triggered left ventricular (LV) pacing for chronic heart failure (CHF). METHODS: Thirty patients who were eligible for the Class I indication of CRT were enrolled and the informed consents were signed. Left ventricular ejection fraction (LVEF), diastolic mitral flow velocity time integral (VTI), mitral regurgitation flow VTI, and aortic valve flow VTI were measured with GE Vivid 7 (GE Medical, Milwaukee, WI, USA) before and after CRT. The echocardiographic measurements and the average annual costs of the device use were compared. RESULTS: The duration of QRS complex, the length of time used for optimization, and the average annual cost of the device use under RV sense triggered LV pacing were significantly less than that under standard biventricular (BiV) pacing (p < 0.01), while the average battery lifetime was longer. Subgroup analysis showed that LVEF, diastolic mitral flow VTI, and aortic valve flow VTI under RV sense triggered LV pacing were greater than that under standard BiV pacing with right or LV pre-activation. The average battery lifetime was significantly longer and the average annual cost of the device use was less. The mitral regurgitation flow VTI under RV sense triggered LV pacing was less than that under standard BiV pacing with RV pre-activation. CONCLUSIONS: RV sense triggered LV provides benefits for CHF patients over standard CRT in terms of maintaining the physiological atrio-ventricular delay of atrio-ventricular node and improving the acute hemodynamic effects.

Randomized and double-blind controlled clinical trial of extracorporeal cardiac shock wave therapy for coronary heart disease.

Our aim was to evaluate the safety and effectiveness of extracorporeal cardiac shock wave therapy (CSWT) for the patients with coronary heart disease (CHD) using a randomized, double-blind, controlled clinical trial design. Twenty-five patients with CHD were enrolled in this study. Fourteen of the patients were randomized into the CSWT group and 11 into the control group. We applied the CSWT procedure to each patient by using nine shock treatments during 3 months, but the shock wave (SW) energy was only applied to the patients in the CSWT group and not to the patients in the control group. Technetium-99m sestamibi myocardial perfusion, fluorine-18 fluorodeoxyglucose myocardial metabolism single-photon emission computed tomography (SPECT), and two-dimensional echocardiography were performed to identify segments of myocardial ischemia, myocardial viability, and ejection fraction before and after CSWT. We also followed the patients to evaluate adverse effects. After CSWT, the New York Heart Association class, the Canadian Cardiovascular Society angina scale, nitroglycerin dosage, myocardial perfusion and myocardial metabolic imaging scores of dual-isotope SPECT in the CSWT group were reduced significantly (P = 0.019, 0.027, 0.039, 0.000, 0.001, respectively), and the Seattle Angina Questionnaire scale, 6-min walking test, and left ventricular ejection fraction were increased significantly (P = 0.021, 0.024, 0.016, respectively) compared with those before the SW treatment. All of the parameters in the control group did not change significantly after the treatment (all P > 0.05). No serious adverse effects of CSWT were observed. Cardiac shock wave therapy is a safe and effective treatment for CHD patients.

A modified regimen of extracorporeal cardiac shock wave therapy for treatment of coronary artery disease.

BACKGROUND: Cardiac shock wave therapy (CSWT) improves cardiac function in patients with severe coronary artery disease (CAD). We aimed to evaluate the clinical outcomes of a new CSWT treatment regimen. METHODS: The 55 patients with severe CAD were randomly divided into 3 treatment groups. The control group (n = 14) received only medical therapy. In group A ( n = 20), CSWT was performed 3 times within 3 months. In group B ( n = 21), patients underwent 3 CSWT sessions/week, and 9 treatment sessions were completed within 1 month. Primary outcome measurement was 6-minute walk test (6MWT). Other measurements were also evaluated. RESULTS: The 6MWT, CCS grading of angina, dosage of nitroglycerin, NYHA classification, and SAQ scores were improved in group A and B compared to control group. CONCLUSIONS: A CSWT protocol with 1 month treatment duration showed similar therapeutic efficacy compared to a protocol of 3 months duration. CLINICAL TRIAL REGISTRY: We have registered on ClinicalTrials.gov, the protocol ID is CSWT IN CHINA.

[Effects of extracorporeal cardiac shock wave therapy in patients with ischemic heart failure].

OBJECTIVE: To evaluate the feasibility, safety and efficiency of extracorporeal cardiac shock wave therapy (CSWT) in patients with ischemic heart failure. METHODS: Fifty patients with ischemic heart failure and left ventricular ejection fraction (LVEF) < 50% were randomized to CSWT (shots/spot at 0.09 mJ/mm(2) for 9 spots, 9 times within 3 month) or control group. Dual isotope simultaneous acquisition single-photon emission computed tomography with (99)Tc(m)-sestamibi/(18)F-fluorodeoxyglucose ((99)Tc(m)-MIBI/(18)F-FDG) was performed before randomization and at 1 month after CSWT/control to locate and evaluate viable myocardium region. Canadian cardiovascular society (CCS) class sores, NYHA, Seattle Angina Questionnaire (SAQ), 6-min walk test (6 MWT), left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD) and the dosage of nitroglycerin use were compared between two groups at each time point. RESULTS: All patients completed the study protocol without procedural complications. At 1 month, patients in CSWT group experienced improvement in NYHA (P < 0.01), CCS (P < 0.01), SAQ (P = 0.021), 6 MWT (P = 0.012) and dosage of nitroglycerin use (P < 0.01) compared to baseline. LVEF [45.0 (39.0, 48.0) vs. 47.0 (42.0, 50.0) P = 0.001], LVEDD [58.0 (56.0, 59.0) vs. 56.0 (55.0, 58.0) P = 0.002], summed perfused score [23.0 (20.5, 24.5) vs. 20.0 (18.0, 22.0) P < 0.01] and metabolic score [25.0 (23.0, 26.0) vs. 24.0 (21.5, 25.0) P = 0.028] were also improved in CSWT group. All these parameters remained unchanged in control group between baseline and at 1 month. CSWT was independent factor for improved cardiac function, quality of life and echocardiography parameters after adjusting for known factors which might affect outcome. CONCLUSION: CSWT could improve symptom, cardiac function, quality of life and exercise tolerance in patients with ischemic heart failure, CSWT might serve as a new, non-invasive, safe and efficient therapy for these patients.