Agreement of ejection fraction measured by coronary computed tomography (CT) and cardiac ultrasound in evaluating patients with chronic heart failure: an observational comparative study.

Background: Cardiac ultrasound is one of the most important examinations in cardiovascular medicine, but the technical requirements for the operator are relatively high, which to some extent affects the scope of its use. This study was dedicated to investigating the agreement of ejection fraction between coronary computed tomography (CT) and cardiac ultrasound and diagnostic performance in evaluating the clinical diagnosis of patients with chronic heart failure. Methods: We conducted a single-center-based retrospective study including 343 consecutive patients enrolled between January 2019 to April 2020, all of whom presented with suspected symptoms of heart failure within one month. All enrolled cases performed cardiac ultrasound and coronary CT scans. The CT images were analyzed using accurate left ventricle (AccuLV) artificial intelligence (AI) software to calculate the ejection fraction-computed tomography (EF-CT) and it was compared with the ejection fraction (EF) obtained based on ultrasound. Cardiac insufficiency was determined if the EF measured by ultrasound was below 50%. Diagnostic performance analysis, correlation analysis and Bland-Altman plot were used to compare agreement between EF-CT and CT. Results: Of the 319 successfully performed patients, 220 (69%) were identified as cardiac insufficiency. Quantitative consistency analysis showed a good correlation between EF-CT and EF values in all cases (R square =0.704, r=0.837). Bland-Altman analysis showed mean bias of 6.6%, mean percentage error of 27.5% and 95% limit of agreement of -17% to 30% between EF and EF-CT. The results of the qualitative diagnostic study showed that the sensitivity and specificity of EF measured by coronary CT reached a high level of 91% [95% confidence interval (CI): 86-94%], and the positive diagnostic value was up to 96% (95% CI: 92-98%). Conclusions: The EF-CT and EF have excellent agreement, and AccuLV-based AI left ventricular function analysis software perhaps can be used as a clinical diagnostic reference.

Transcriptome Expression Profiling Reveals the Molecular Response to Salt Stress in Gossypium anomalum Seedlings.

Some wild cotton species are remarkably tolerant to salt stress, and hence represent valuable resources for improving salt tolerance of the domesticated allotetraploid species Gossypium hirsutum L. Here, we first detected salt-induced stress changes in physiological and biochemical indexes of G. anomalum, a wild African diploid cotton species. Under 350 mmol/L NaCl treatment, the photosynthetic parameters declined significantly, whereas hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents increased. Catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) activity and proline (PRO) content also significantly increased, reaching peak values at different stages of salt stress. We used RNA-Seq to characterize 15,476 differentially expressed genes in G. anomalum roots after 6, 12, 24, 72, and 144 h of salt stress. Gene Ontology enrichment analysis revealed these genes to be related to sequence-specific DNA and iron ion binding and oxidoreductase, peroxidase, antioxidant, and transferase activity; meanwhile, the top enriched pathways from the Kyoto Encyclopedia of Genes and Genomes database were plant hormone signal transduction, phenylpropanoid biosynthesis, fatty acid degradation, carotenoid biosynthesis, zeatin biosynthesis, starch and sucrose metabolism, and MAPK signaling. A total of 1231 transcription factors were found to be expressed in response to salt stress, representing ERF, MYB, WRKY, NAC, C2H2, bZIP, and HD-ZIP families. Nine candidate genes were validated by quantitative real-time PCR and their expression patterns were found to be consistent with the RNA-Seq data. These data promise to significantly advance our understanding of the molecular response to salt stress in Gossypium spp., with potential value for breeding applications.

Insulin augments angiotensin II-induced myocardial fibrosis via the MEK/STAT3 pathway.

Regular insulin therapy is significantly related to worse cardiovascular outcomes in patients with type 2 diabetes and heart failure. However, the mechanisms of the causal relationship remain unclear. In this study, we observed the effect of insulin on cardiac structure and function and found that insulin dramatically augmented angiotensin II (Ang II)-induced cardiac dysfunction, as well as the proliferation and collagen production of primary cardiac fibroblasts. Total STAT3 expression, but not activation was stimulated by insulin; the effect of insulin on Ang II-induced fibrosis disappeared when STAT3 was blocked and could be entirely suppressed by the MEK inhibitor PD0325901. Our findings suggest a noninsulin-dependent glucose-lowering regimen for patients with type 2 diabetes (T2DM) and heart failure (HF).

Application of an improved whale optimization algorithm in time-optimal trajectory planning for manipulators.

To address the issues of unstable, non-uniform and inefficient motion trajectories in traditional manipulator systems, this paper proposes an improved whale optimization algorithm for time-optimal trajectory planning. First, an inertia weight factor is introduced into the surrounding prey and bubble-net attack formulas of the whale optimization algorithm. The value is controlled using reinforcement learning techniques to enhance the global search capability of the algorithm. Additionally, the variable neighborhood search algorithm is incorporated to improve the local optimization capability. The proposed whale optimization algorithm is compared with several commonly used optimization algorithms, demonstrating its superior performance. Finally, the proposed whale optimization algorithm is employed for trajectory planning and is shown to be able to produce smooth and continuous manipulation trajectories and achieve higher work efficiency.

YAP at the Crossroads of Biomechanics and Drug Resistance in Human Cancer.

Biomechanical forces are of fundamental importance in biology, diseases, and medicine. Mechanobiology is an emerging interdisciplinary field that studies how biological mechanisms are regulated by biomechanical forces and how physical principles can be leveraged to innovate new therapeutic strategies. This article reviews state-of-the-art mechanobiology knowledge about the yes-associated protein (YAP), a key mechanosensitive protein, and its roles in the development of drug resistance in human cancer. Specifically, the article discusses three topics: how YAP is mechanically regulated in living cells; the molecular mechanobiology mechanisms by which YAP, along with other functional pathways, influences drug resistance of cancer cells (particularly lung cancer cells); and finally, how the mechanical regulation of YAP can influence drug resistance and vice versa. By integrating these topics, we present a unified framework that has the potential to bring theoretical insights into the design of novel mechanomedicines and advance next-generation cancer therapies to suppress tumor progression and metastasis.

Deep Multi-Modal Discriminative and Interpretability Network for Alzheimer's Disease Diagnosis.

Multi-modal fusion has become an important data analysis technology in Alzheimer's disease (AD) diagnosis, which is committed to effectively extract and utilize complementary information among different modalities. However, most of the existing fusion methods focus on pursuing common feature representation by transformation, and ignore discriminative structural information among samples. In addition, most fusion methods use high-order feature extraction, such as deep neural network, by which it is difficult to identify biomarkers. In this paper, we propose a novel method named deep multi-modal discriminative and interpretability network (DMDIN), which aligns samples in a discriminative common space and provides a new approach to identify significant brain regions (ROIs) in AD diagnosis. Specifically, we reconstruct each modality with a hierarchical representation through multilayer perceptron (MLP), and take advantage of the shared self-expression coefficients constrained by diagonal blocks to embed the structural information of inter-class and the intra-class. Further, the generalized canonical correlation analysis (GCCA) is adopted as a correlation constraint to generate a discriminative common space, in which samples of the same category gather while samples of different categories stay away. Finally, in order to enhance the interpretability of the deep learning model, we utilize knowledge distillation to reproduce coordinated representations and capture influence of brain regions in AD classification. Experiments show that the proposed method performs better than several state-of-the-art methods in AD diagnosis.

Multimodal Triplet Attention Network for Brain Disease Diagnosis.

Multi-modal imaging data fusion has attracted much attention in medical data analysis because it can provide complementary information for more accurate analysis. Integrating functional and structural multi-modal imaging data has been increasingly used in the diagnosis of brain diseases, such as epilepsy. Most of the existing methods focus on the feature space fusion of different modalities but ignore the valuable high-order relationships among samples and the discriminative fused features for classification. In this paper, we propose a novel framework by fusing data from two modalities of functional MRI (fMRI) and diffusion tensor imaging (DTI) for epilepsy diagnosis, which effectively captures the complementary information and discriminative features from different modalities by high-order feature extraction with the attention mechanism. Specifically, we propose a triple network to explore the discriminative information from the high-order representation feature space learned from multi-modal data. Meanwhile, self-attention is introduced to adaptively estimate the degree of importance between brain regions, and the cross-attention mechanism is utilized to extract complementary information from fMRI and DTI. Finally, we use the triple loss function to adjust the distance between samples in the common representation space. We evaluate the proposed method on the epilepsy dataset collected from Jinling Hospital, and the experiment results demonstrate that our method is significantly superior to several state-of-the-art diagnosis approaches.

Combining 3D Magnetic Force Actuator and Multi-Functional Fluorescence Imaging to Study Nucleus Mechanobiology.

A fundamental question in mechanobiology is how living cells sense extracellular mechanical stimuli in the context of cell physiology and pathology. The cellular mechano-sensation of extracellular mechanical stimuli is believed to be through the membrane receptors, the associated protein complex, and the cytoskeleton. Recent advances in mechanobiology demonstrate that the cell nucleus in cytoplasm itself can independently sense mechanical stimuli simultaneously. However, a mechanistic understanding of how the cell nucleus senses, transduces, and responds to mechanical stimuli is lacking, mainly because of the technical challenges in accessing and quantifying the nucleus mechanics by conventional tools. This paper describes the design, fabrication, and implementation of a new magnetic force actuator that applies precise and non-invasive 3D mechanical stimuli to directly deform the cell nucleus. Using CRISPR/Cas9-engineered cells, this study demonstrates that this tool, combined with high-resolution confocal fluorescent imaging, enables the revelation of the real-time dynamics of a mechano-sensitive yes-associated protein (YAP) in single cells as a function of nucleus deformation. This simple method has the potential to bridge the current technology gap in the mechanobiology community and provide answers to the knowledge gap that exists in the relation between nucleus mechanotransduction and cell function.

Acupuncture for Hypertension in Animal Models: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this study was to summarize and evaluate the efficacy of acupuncture in hypertension animal study. METHODS: Studies were searched from six databases, including Medline, Embase, Chinese National Knowledge Infrastructure, Wanfang Data, VIP information database, and Chinese Biomedical Literature Database. Study quality of each included study was evaluated according to the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines, and the risk of bias was evaluated by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were selected as outcomes. Meta-analyses were performed using Stata 12.0 software. The effect size was calculated by combining SBP/DBP/MAP data with the random effects model, respectively. RESULTS: 67 studies containing 1522 animals were included. According to the ARRIVE guideline, 8 items were assessed as poor and 4 items were assessed as excellent. According to the SYRCLE tool, all studies were judged as having high risk of bias. Compared with the hypertension group, the pooled results showed significant antihypertension effects of acupuncture for SBP, DBP, and MAP. Similarly, compared with the sham-acupuncture group, the pooled results showed significant antihypertension effects of acupuncture for SBP, DBP, and MAP. CONCLUSION: Although pooled data suggested that the acupuncture group was superior to the hypertension group or sham-acupuncture group for SBP/DBP/MAP, the presentation of poor methodological quality, high risk of bias, and heterogeneity deserves cautious interpretation of the results.

Optimal antiplatelet therapy for prevention of gastrointestinal injury evaluated by ANKON magnetically controlled capsule endoscopy: Rationale and design of the OPT-PEACE trial.

BACKGROUND: Gastrointestinal injury is a common complication in patients treated with antiplatelet agents after percutaneous coronary intervention (PCI). However, the effects of different antiplatelet regimens on the incidence and severity of gastrointestinal injury have not been well studied, principally due to the lack of a low-risk sensitive and accurate detection system. TRIAL DESIGN: OPT-PEACE is a multicenter, randomized, double-blind, placebo-controlled trial. Gastrointestinal injury will be evaluated with the ANKON magnetically controlled capsule endoscopy system (AMCE), a minimally invasive approach for detecting mucosal lesions in the stomach, duodenum and small intestine. Patients without AMCE-detected gastrointestinal erosions, ulceration or bleeding after drug-eluting stent implantation are enrolled and treated with open-label aspirin (100 mg/d) plus clopidogrel (75 mg/d) for 6 months. Thereafter, 480 event-free patients will undergo repeat AMCE and are randomly assigned in a 1:1:1 ratio to receive aspirin plus clopidogrel, aspirin plus placebo or clopidogrel plus placebo for an additional 6 months. A final AMCE is performed at 12 months. The primary endpoint is the incidence of gastric or intestinal mucosal lesions (erosions, ulceration, or bleeding) within 12 months after enrollment. CONCLUSIONS: OPT-PEACE is the first study to investigate the incidence and severity of gastrointestinal injury in patients receiving different antiplatelet therapy regimens after stent implantation. This trial will inform clinical decision-making for personalized antiplatelet therapy post-PCI.

Impact of Baseline Bleeding Risk on Efficacy and Safety of Ticagrelor versus Clopidogrel in Chinese Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

BACKGROUND: There was still conflict on the antithrombotic advantage of ticagrelor versus clopidogrel among East Asian population with acute coronary syndrome (ACS). We considered that the baseline bleeding risk might be an undetected key factor that significantly affected the efficacy of ticagrelor. METHODS: A total of 20,816 serial patients who underwent percutaneous coronary intervention (PCI) from October 2011 to August 2014 in the General Hospital of Shenyang Military Region were enrolled in the present study. Patients receiving ticagrelor or clopidogrel were further subdivided according to basic bleeding risk. The primary outcome was net adverse clinical events (NACEs) defined as major adverse cardiac or cerebral events (MACCE, including all-cause death, myocardial infarction, ischemia-driven target vessel revascularization, or stroke) and any bleeding during 1-year follow-up. Comparison between ticagrelor and clopidogrel was adjusted by propensity score matching (PSM). RESULTS: Among the 20,816 eligible PCI patients who were included in this study, there were 1578 and 779 patients in the clopidogrel and ticagrelor groups, respectively, after PSM, their clinical parameters were well matched. Patients receiving ticagrelor showed comparable NACE risk compared with those treated by clopidogrel (5.3% vs. 5.1%, P = 0.842). Furthermore, ticagrelor might reduce the MACCE risk in patients with low bleeding risk but increase MACCE in patients with moderate-to-high bleeding potential (ticagrelor vs. clopidogrel, low bleeding risk: 2.5% vs. 4.9%, P = 0.022; moderate-to-high bleeding risk: 4.8% vs. 3.0%, P = 0.225; interaction P = 0.021), with vast differences in all bleeding (low bleeding risk: 1.5% vs. 0.8%, P = 0.210; moderate-to-high bleeding risk: 4.8% vs. 3.0%, P = 0.002; interaction P = 0.296). CONCLUSION: Among real-world Chinese patients with ACS treated by PCI, ticagrelor only showed superior efficacy in patients with low bleeding risk but lost its advantage in patients with moderate-to-high bleeding potential.

Pharmacodynamics and pharmacokinetics of ticagrelor vs. clopidogrel in patients with acute coronary syndromes and chronic kidney disease.

BACKGROUND: Pivotal clinical trials found that ticagrelor reduced ischaemic complications to a greater extent than clopidogrel, and also that the benefit gradually increased with the reduction in creatinine clearance. However, the underlying mechanisms remains poorly explored. METHODS: This was a single-centre, prospective, randomized clinical trial involving 60 hospitalized Adenosine Diphosphate (ADP) P2Y12 receptor inhibitor-naïve patients with chronic kidney disease (CKD) (estimated glomerular filtration rate <60 ml min-1 1.73 m-2 ) and non-ST-elevation acute coronary syndromes (NSTE-ACS). Eligible patients were randomly assigned in a 1:1 ratio to receive ticagrelor (180 mg loading dose, then followed by 90 mg twice daily) or clopidogrel (600 mg loading dose, then followed by 75 mg once daily). The primary endpoint was the P2Y12 reactive unit (PRU) value assessed by VerifyNow at 30 days. The plasma concentrations of ticagrelor and clopidogrel and their active metabolites were measured in the first 10 patients in each group at baseline, and at 1 h, 2 h, 4 h, 8 h, 12 h and 24 h after the loading dose. RESULTS: Baseline characteristics were well matched between the two groups. Our results indicated a markedly lower PRU in patients treated with ticagrelor vs. clopidogrel at 30 days (32.6 ± 11.29 vs. 203.7 ± 17.92; P < 0.001) as well as at 2 h, 8 h and 24 h after the loading dose (P < 0.001). Ticagrelor and its active metabolite AR-C124910XX showed a similar time to reach maximum concentration (Cmax ) of 8 h, with the maximum concentration (Cmax ) of 355 (242.50-522.00) ng ml-1 and 63.20 (50.80-85.15) ng ml-1 , respectively. Both clopidogrel and its active metabolite approached the Cmax at 2 h, with a similar Cmax of 8.67 (6.64-27.75) ng ml-1 vs. 8.53 (6.94-15.93) ng ml-1 . CONCLUSION: Ticagrelor showed much more potent platelet inhibition in comparison with clopidogrel in patients with CKD and NSTE-ACS.

Effect of postprocedural full-dose infusion of bivalirudin on acute stent thrombosis in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: Outcomes in a large real-world population.

AIM: This study aimed to evaluate the effect of prolonged full-dose bivalirudin infusion in real-world population with ST-elevation myocardial infarction (STEMI). BACKGROUND: Subgroup data as well as meta-analysis from randomized clinical trials have shown the potency of postprocedural full-dose infusion (1.75 mg/kg/h) of bivalirudin on attenuating acute stent thrombosis (ST) after primary percutaneous coronary intervention (PCI). METHODS: In this multicenter retrospective observational study, 2047 consecutive STEMI patients treated with bivalirudin during primary PCI were enrolled in 65 Chinese centers between July 2013 and May 2016. The primary outcome was acute ST defined as ARC definite/probable within 24 hours after the index procedure, and the secondary endpoints included total ST, major adverse cardiac or cerebral events (MACCE, defined as death, reinfarction, stroke, and target vessel revascularization), and any bleeding at 30 days. RESULTS: Among 2047 STEMI patients, 1123 (54.9%) were treated with postprocedural bivalirudin full-dose infusion (median 120 minutes) while the other 924 (45.1%) received low-dose (0.25 mg/kg/h) or null postprocedural infusion. A total of three acute ST (0.3%) occurred in STEMI patients with none or low-dose prolonged infusion of bivalirudin, but none was observed in those treated with post-PCI full-dose infusion (0.3% vs 0.0%, P=.092). Outcomes on MACCE (2.1% vs 2.7%, P=.402) and total bleeding (2.1% vs 1.4%, P=.217) at 30 days showed no significant difference between the two groups, and no subacute ST was observed. CONCLUSION: Post-PCI full-dose bivalirudin infusion is safe and has a trend to protect against acute ST in STEMI patients undergoing primary PCI in real-world settings.

Efficacy and safety of a biodegradable polymer Cobalt-Chromium sirolimus-eluting stent (EXCROSSAL) in treating de novo coronary artery disease: A pooled analysis of the CREDIT II and CREDIT III trials.

BACKGROUND: The safety and efficacy of the second-generation biodegradable polymer Cobalt-Chromium sirolimus-eluting stent (EXCEL2) in daily clinical practice remains unknown. Additionally, to meet the China Food and Drug Administration requirements, we conducted an objective performance criterion study from the CREDIT II and CREDIT III trials. METHODS: CREDIT II was a randomized trial comparing the EXCEL2 versus EXCEL stent in patients with up to 2 de novo coronary lesions. CREDIT III was a prospective, single-arm study evaluating the efficacy and safety of EXCEL2 in broad types of de novo coronary artery lesions. This pooled analysis included patients in the CREDIT III and EXCEL2 arm of the CREDIT II trial. The primary outcome was 12-month target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TV-MI), and clinical indicated target lesion revascularization (CI-TLR). The patient-oriented composite endpoint (PoCE) of all-cause death, all MI, or any revascularization was also analyzed. RESULTS: A total of 833 patients were included, consisting of 625 in the CREDIT III trial and 208 in the EXCEL2 arm of the CREDIT II trial. Twelve-month TLF occurred in 6.1% patients, cardiac death in 0.4%, TV-MI in 5%, and CI-TLR in 1.1%. Additionally, 64 (7.7%) PoCE and 3 probable late stent thromboses (0.4%) were recorded. CONCLUSION: EXCEL2 stent met the objective performance criterion on efficacy and safety with a low level of 12-month TLF as well as stent thrombosis when treating patients with de novo coronary lesions. © 2017 Wiley Periodicals, Inc.

HNF-4alpha Negatively Regulates Hepcidin Expression Through BMPR1A in HepG2 Cells.

Hepcidin synthesis is reported to be inadequate according to the body iron store in patients with non-alcoholic fatty liver disease (NAFLD) undergoing hepatic iron overload (HIO). However, the underlying mechanisms remain unclear. We hypothesize that hepatocyte nuclear factor-4α (HNF-4α) may negatively regulate hepcidin expression and contribute to hepcidin deficiency in NAFLD patients. The effect of HNF-4α on hepcidin expression was observed by transfecting specific HNF-4α small interfering RNA (siRNA) or plasmids into HepG2 cells. Both direct and indirect mechanisms involved in the regulation of HNF-4α on hepcidin were detected by real-time PCR, Western blotting, chromatin immunoprecipitation (chIP), and reporter genes. It was found that HNF-4α suppressed hepcidin messenger RNA (mRNA) and protein expressions in HepG2 cells, and this suppressive effect was independent of the potential HNF-4α response elements. Phosphorylation of SMAD1 but not STAT3 was inactivated by HNF-4α, and the SMAD4 response element was found essential to HNF-4α-induced hepcidin reduction. Neither inhibitory SMADs, SMAD6, and SMAD7 nor BMPR ligands, BMP2, BMP4, BMP6, and BMP7 were regulated by HNF-4α in HepG2 cells. BMPR1A, but not BMPR1B, BMPR2, ActR2A, ActR2B, or HJV, was decreased by HNF-4α, and HNF4α-knockdown-induced stimulation of hepcidin could be entirely blocked when BMPR1A was interfered with at the same time. In conclusion, the present study suggests that HNF-4α has a suppressive effect on hepcidin expression by inactivating the BMP pathway, specifically via BMPR1A, in HepG2 cells.

Efficiency and safety of bivalirudin in patients undergoing emergency percutaneous coronary intervention via radial access: A subgroup analysis from the bivalirudin in acute myocardial infarction versus heparin and GPI plus heparin trial.

OBJECTIVES: To explore the efficiency and safety of bivalirudin in patients undergoing emergency percutaneous coronary intervention via radial access. BACKGROUND: Bivalirudin reduces bleeding risks over heparin in patients undergoing PCI. However, bleeding advantages of bivalirudin in patients undergoing transradial intervention is uncertain. METHODS: In the BRIGHT trial, 1,723 patients underwent emergency PCI via radial access, with 576 patients in the bivalirudin arm, 576 in the heparin arm and 571 in the heparin plus tirofiban arm. The primary outcome was 30-day net adverse clinical event (NACE), defined as a composite of major cardiac and cerebral events or any bleeding. RESULTS: 30-day NACE occurred in 5.7% with bivalirudin, 7.8% with heparin alone (vs. bivalirudin, P = 0.159), and 10.3% with heparin plus tifofiban (vs. bivalirudin, P = 0.004). The 30-day bleeding rate was 0.9% for bivalirudin, 2.3% for heparin (vs. bivalirudin, P = 0.057), and 5.8% for heparin plus tirofiban (vs. bivalirudin, P < 0.001). Major cardiac and cerebral events (4.9 vs. 5.7 vs. 4.6%, P = 0.899), stent thrombosis (0.5 vs. 0.5 vs. 0.7%, P = 0.899) and acquired thrombocytopenia (0.2 vs. 0.5 vs. 0.9%, P = 0.257) at 30 days were similar among three arms. The interaction test for PCI access and randomized treatment showed no significance on all bleeding (P > 0.05). CONCLUSIONS: The bleeding benefit of bivalirudin was independent of artery access. Bivalirudin lead to statistical reduction on bleeding risks in comparison to heparin plus tirofiban, and only small numerical difference in comparison to heparin, with comparable risks of ischemic events and stent thrombosis in patients with acute myocardial infarction (AMI) undergoing emergency transradial PCI. © 2016 Wiley Periodicals, Inc.

Impacts of anemia on 3-year ischemic events in patients undergoing percutaneous coronary intervention: a propensity-matched study.

BACKGROUND: Anemia correlates with worse outcomes in patients undergoing percutaneous coronary intervention (PCI), improved anemia can improve the outcomes in patients who underwent PCI. But the influence of anemia on long-term ischemic events after PCI remains unknown. METHODS: We analyzed 8,825 consecutive patients who underwent PCI at General Hospital of Shenyang Military Region and identified 581 patients with anemia. Patients (anemia vs. no anemia) were compared using a propensity score analysis to best match between groups. The main outcome of this study is 3-year ischemic events after PCI, the secondary outcome of this study is 3-year mortality and major adverse cardiac events (MACE) after PCI. RESULTS: Compared with nonanemic patients, anemic patients were often female (38.90% vs. 14.51%) and elder patients (66.44% vs. 34.95%). Anemic patients have lower left ventricular ejection fraction (LVEF) and creatinine clearance (Ccr) and were more likely to have history of cardiovascular and cerebrovascular diseases, hypertension, peripheral vascular diseases (PVD) (P<0.05). However, the prevalences of diabetes and hyperlipidemia were lower in anemic patients (P<0.01). Anemia was an independent predictor for 3-year ischemic events [hazard ratio (HR): 2.20, 95% confidence intervals (CI): 1.61-3.00, P<0.01], 3-year mortality (HR: 3.58, 95% CI: 1.75-7.32, P<0.01) and 3-year MACE (HR: 2.14, 95% CI: 1.64-2.79, P<0.01) after PCI in post-match samples. The incidence of 3-year ischemic events was 41.0% and 19.3% in anemic and nonanemic patients, respectively. CONCLUSIONS: Anemia is an independent predictor for 3-year ischemic events, 3-year mortality and 3-year MACE in patients who underwent PCI. Further studies need to explore the impact of the pathogenesis and progress, prevention and therapy of anemia on the outcome of patients undergoing PCI.

Impact of anemia on long-term ischemic events and bleeding events in patients undergoing percutaneous coronary intervention: a system review and meta-analysis.

BACKGROUND: Data focused on the ischemic events and bleeding events are still limited. We systematically reviewed the current available literature to investigate whether anemia increase incidence of long-term ischemic events and long-term bleeding events in patients undergoing PCI. METHODS: PubMed and Embase were searched for case-control studies regarding the impact of anemia on long-term outcomes in patients undergoing percutaneous coronary intervention (PCI). The primary outcome was long-term ischemic events and long-term bleeding events. Mantel-Haenszel method with random effects model or fixed effects model was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Seventeen studies involving 68,528 patients (17,123 anemic patients and 51,405 non-anemic patients) were included. Pooled analysis suggested that anemic patients were at higher risk for long-term composite ischemic events (OR: 1.95, 95% CI, 1.21-3.14, P<0.01, I(2)=84%), long-term reinfarction (0R: 1.63, 95% CI, 1.16-2.28, P<0.01, I(2)=82%) and long-term bleeding events (OR: 2.89, 95% CI, 1.68-4.98, P<0.001, I(2)=89%). Anemia was also associated with long-term mortality (OR: 3.20, 95% CI, 2.72-3.75, P<0.01, I(2)=65%) and major adverse cardiac events (MACE) (OR: 2.06, 95% CI, 1.48-2.86, P<0.01, I(2)=91%). CONCLUSIONS: Anemic patients undergoing PCI are at higher risk for both long-term ischemic events and bleeding events, and also at higher risk for long-term mortality and MACE. There's a need for further clarification and consistency regarding dosage, timing and duration of antithrombotic therapy for the prevention of ischemic events and bleeding events in anemic patients.

Hyperinsulinemia induces hepatic iron overload by increasing liver TFR1 via the PI3K/IRP2 pathway.

Dysmetabolic iron overload syndrome (DIOS) is frequently observed, but the underlying mechanism remains unclear. We propose the hypothesis that hyperinsulinemia, a common characteristic of DIOS, may stimulate liver transferrin receptor 1 (TFR1) expression via the PI3K/iron regulatory protein 2 (IRP2) pathway, leading to the occurrence of DIOS. The hepatic iron content, serum iron parameters, and expressions of TFRs and IRPs in the liver were determined in rats with temporary or long-lasting hyperinsulinemia induced by acute or chronic administration of insulin. The effect of insulin on TFR1 expression and its molecular mechanism were determined in HL-7702 cells in vitro. It was found that long-lasting hyperinsulinemia significantly increased TFR1 expression in the liver and induced mild-to-moderate hepatic iron overload, which was accompanied by a normal level of serum iron. Insulin markedly upregulated both protein and mRNA levels of TFR1 in HL-7702 cells. The stability of TFR1 mRNA stability, together with expression of IRPs expression, were both significantly increased by insulin treatment. Insulin-induced TFR1 expression was blocked by IRP2, but not by IRP1 interference, and disappeared when HL-7702 cells were pretreated with LY294002, triciribine hydrate, or rapamycin. In conclusion, the findings of this study indicate that hyperinsulnemia could induce hepatic iron overload by upregulating liver TFR1 via the PI3K/AKT/mTOR/IRP2 pathway, which may be one of the main reasons for the occurrence of DIOS.