Mechanism of Nrf2 in the treatment of ulcerative colitis via regulating macrophage polarization. / Nrf2é€šè¿‡è°ƒæŽ§å·¨å™¬ç»†èƒžæžåŒ–æ²»ç–—æºƒç–¡æ€§ç»“è‚ ç‚Žçš„æœºåˆ¶.

Ulcerative colitis (UC) is an inflammatory bowel disease induced by multiple factors, which causes abnormal activation of intestinal immune cells and excessive release of antibodies and inflammatory factors, repeatedly damaging the intestinal mucosa. Macrophages, as innate intestinal immune cells, often maintain the balance of M1/M2 macrophages polarization to normalize the regression inflammation, and the imbalance of their polarization will cause repeated damage of intestinal mucosa and persistent inflammation, which is a main cause of UC. Nuclear factor E2-related factor 2 (Nrf2), as an important regulator of antioxidant and anti-inflammatory, is often used as a target for the treatment of autoimmune diseases.Nrf2 alleviates intestinal high oxidative stress and inflammatory factors by balancing macrophage polarization, which may be of great significance for the prevention and treatment of UC. Summarizing the mechanism of macrophage polarization imbalance on the course of UC and the possible regulatory mechanism of Nrf2 may provide basis for the development of UC targeted therapeutic drugs.

The prediction of asymptomatic carotid atherosclerosis with electronic health records: a comparative study of six machine learning models.

BACKGROUND: Screening carotid B-mode ultrasonography is a frequently used method to detect subjects with carotid atherosclerosis (CAS). Due to the asymptomatic progression of most CAS patients, early identification is challenging for clinicians, and it may trigger ischemic stroke. Recently, machine learning has shown a strong ability to classify data and a potential for prediction in the medical field. The combined use of machine learning and the electronic health records of patients could provide clinicians with a more convenient and precise method to identify asymptomatic CAS. METHODS: Retrospective cohort study using routine clinical data of medical check-up subjects from April 19, 2010 to November 15, 2019. Six machine learning models (logistic regression [LR], random forest [RF], decision tree [DT], eXtreme Gradient Boosting [XGB], Gaussian Naïve Bayes [GNB], and K-Nearest Neighbour [KNN]) were used to predict asymptomatic CAS and compared their predictability in terms of the area under the receiver operating characteristic curve (AUCROC), accuracy (ACC), and F1 score (F1). RESULTS: Of the 18,441 subjects, 6553 were diagnosed with asymptomatic CAS. Compared to DT (AUCROC 0.628, ACC 65.4%, and F1 52.5%), the other five models improved prediction: KNN + 7.6% (0.704, 68.8%, and 50.9%, respectively), GNB + 12.5% (0.753, 67.0%, and 46.8%, respectively), XGB + 16.0% (0.788, 73.4%, and 55.7%, respectively), RF + 16.6% (0.794, 74.5%, and 56.8%, respectively) and LR + 18.1% (0.809, 74.7%, and 59.9%, respectively). The highest achieving model, LR predicted 1045/1966 cases (sensitivity 53.2%) and 3088/3566 non-cases (specificity 86.6%). A tenfold cross-validation scheme further verified the predictive ability of the LR. CONCLUSIONS: Among machine learning models, LR showed optimal performance in predicting asymptomatic CAS. Our findings set the stage for an early automatic alarming system, allowing a more precise allocation of CAS prevention measures to individuals probably to benefit most.

Platelet-neutrophil interaction aggravates vascular inflammation and promotes the progression of atherosclerosis by activating the TLR4/NF-κB pathway.

Platelet-neutrophil interaction is well known for its role in inflammatory diseases; however, its biological role in atherosclerosis (AS) progression remains unclear. Human peripheral blood neutrophils were obtained to compare toll-like receptor 4 (TLR4), tumor necrosis factor α (TNF-α), interleukin (IL)-1ß and myeloid-related proteins 8/14 (Mrp8/14) levels in 22 AS patients with those in 18 healthy controls using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Meanwhile, mouse marrow neutrophils subjected to different treatment were collected for the ELISA assay, cell apoptosis, and Western blot analysis. Normal diet or high-fat diet ApoE-/- mice with or without administration of Mrp8/14 antagonist paquinimod were used for plasma collection to measure total cholesterol, triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, TNF-α, IL-1ß, Mrp8/14, TLR4, and nuclear factor (NF)-κB p65 levels. The results showed that Mrp8/14 and TLR4-mediated inflammatory pathway was activated in neutrophils of AS patients. In vitro experiments demonstrated that platelet-neutrophil interaction promoted the Mrp8/14 release and inhibited neutrophil apoptosis via P-selectin. Furthermore, platelet-neutrophil interaction upregulated TLR4/myeloid differentiation factor 88/NF-κB pathway. Conversely, Mrp8/14/TLR4/NF-κB interference alleviated AS progression. In conclusion, Mrp8/14/TLR4/NF-κB activated by platelet-neutrophil interaction is an important inflammatory signaling pathway for AS pathogenesis.

miR-350-3p Contributes to Age-Associated Impairment of IL-6 Production by Macrophages.

Aging-associated dysfunction of the immune system contributes to the increase in pathophysiological processes that occur with age. Numerous studies have shown that microRNAs regulate immune responses, although their role in age-related macrophage dysfunction remains elusive. Here, we found that miR-350-3p is expressed at lower levels in peritoneal macrophages from aged mice compared with young mice, and that lipopolysaccharide (LPS) stimulation downregulates miR-350-3p expression to a greater extent in young macrophages compared with aged macrophages. Consequently, LPS-stimulated aged macrophages express more miR-350-3p than do similarly treated young macrophages. Luciferase reporter assays showed that interleukin (IL)-6 mRNA is a miR-350-3p target in macrophages. Furthermore, although LPS induces less IL-6 production by aged macrophages than by young macrophages, the aged cell response is rescued by production miR-350-3p inhibition. These findings suggest that miR-350-3p may contribute to age-related impairment of macrophage function and could be a novel target for the treatment of age-related inflammatory diseases.

Effects of thoracic epidural anesthesia on cardiac function and myocardial cell apoptosis in isoproterenol-induced chronic heart failure rats.

OBJECTIVE: This study aimed to investigate the effects of thoracic epidural anesthesia (TEA) on cardiac function and myocardial cell apoptosis in isoproterenol (ISO) induced chronic heart failure (CHF) rats. METHOD: Rats were classified into 4 groups: the healthy control, ISO-induced CHF, ISO + TEA, and sham-treated groups. After 4 weeks, the animals in each group were examined by echocardiography. Invasive hemodynamic measurements were also preformed. RESULTS: Echocardiographic findings suggested that rats in the ISO + TEA group exhibited decreased left ventricular end-systolic (LVES) and left ventricular end-diastolic (LVED), and increased left ventricular ejection fraction (LVEF) and left ventricular shortening fraction (LVFS) compared with rats in the ISO-induced CHF group. Rats in the ISO + TEA group showed improved left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVEDP) compared with rats in the ISO-induced CHF group. Additionally, rats in the ISO + TEA group had significant decrease in LV and RV mass indexes (LVMI and RVMI) compared with rats in the ISO-induced CHF rats. Myocardial ultrastructure in the ISO + TEA group significantly improved compared with the ISO-induced CHF group. TEA significantly reduced the percent of TUNEL-positive cells in the ISO + TEA group compared with the ISO-induced CHF group. Compared with the ISO-induced CHF group, Bcl-2 expression of rats in the ISO + TEA group was significantly increased, while Bax expression was significantly attenuated. CONCLUSION: Our findings suggest that TEA may reduce myocardial apoptosis and decrease extent of structural damage and abnormalities in the myocardium.

Multi-Stage Asynchronous Federated Learning With Adaptive Differential Privacy.

The fusion of federated learning and differential privacy can provide more comprehensive and rigorous privacy protection, thus attracting extensive interests from both academia and industry. However, facing the system-level challenge of device heterogeneity, most current synchronous FL paradigms exhibit low efficiency due to the straggler effect, which can be significantly reduced by Asynchronous FL (AFL). However, AFL has never been comprehensively studied, which imposes a major challenge in the utility optimization of DP-enhanced AFL. Here, theoretically motivated multi-stage adaptive private algorithms are proposed to improve the trade-off between model utility and privacy for DP-enhanced AFL. In particular, we first build two DP-enhanced AFL frameworks with consideration of universal factors for different adversary models. Then, we give a solid analysis on the model convergence of AFL, based on which, DP can be adaptively achieved with high utility. Through extensive experiments on different training models and benchmark datasets, we demonstrate that the proposed algorithms achieve the overall best performances and improve up to 24% test accuracy with the same privacy loss and have faster convergence compared with the state-of-the-art algorithms. Our frameworks provide an analytical way for private AFL and adapt to more complex FL application scenarios.

Multi-Omics Research Accelerates the Clarification of the Formation Mechanism and the Influence of Leaf Color Variation in Tea (Camellia sinensis) Plants.

Tea is a popular beverage with characteristic functional and flavor qualities, known to be rich in bioactive metabolites such as tea polyphenols and theanine. Recently, tea varieties with variations in leaf color have been widely used in agriculture production due to their potential advantages in terms of tea quality. Numerous studies have used genome, transcriptome, metabolome, proteome, and lipidome methods to uncover the causes of leaf color variations and investigate their impacts on the accumulation of crucial bioactive metabolites in tea plants. Through a comprehensive review of various omics investigations, we note that decreased expression levels of critical genes in the biosynthesis of chlorophyll and carotenoids, activated chlorophyll degradation, and an impaired photosynthetic chain function are related to the chlorina phenotype in tea plants. For purple-leaf tea, increased expression levels of late biosynthetic genes in the flavonoid synthesis pathway and anthocyanin transport genes are the major and common causes of purple coloration. We have also summarized the influence of leaf color variation on amino acid, polyphenol, and lipid contents and put forward possible causes of these metabolic changes. Finally, this review further proposes the research demands in this field in the future.

Quantum-aided secure deep neural network inference on real quantum computers.

Deep neural networks (DNNs) are phenomenally successful machine learning methods broadly applied to many different disciplines. However, as complex two-party computations, DNN inference using classical cryptographic methods cannot achieve unconditional security, raising concern on security risks of DNNs' application to sensitive data in many domains. We overcome such a weakness by introducing a quantum-aided security approach. We build a quantum scheme for unconditionally secure DNN inference based on quantum oblivious transfer with an untrusted third party. Leveraging DNN's noise tolerance, our approach enables complex DNN inference on comparatively low-fidelity quantum systems with limited quantum capacity. We validated our method using various applications with a five-bit real quantum computer and a quantum simulator. Both theoretical analyses and experimental results demonstrate that our approach manages to operate on existing quantum computers and achieve unconditional security with a negligible accuracy loss. This may open up new possibilities of quantum security methods for deep learning.

Preparation of a CeO2 ball-core structure and its application in quantum dot sensitized solar cells.

A pomegranate-like nanosphere structure of CeO2 was prepared by a simple one-step hydrothermal method, and the novel CeO2 structure was printed on a TiO2 film to form a scattering layer, which constituted the composite structure of a photoanode in a thin film optoelectronic device. Then ZnCuInSe quantum dots, a ZnS passivation layer and a CuS counter electrode were prepared, and these parts were assembled into quantum dot-sensitized solar cells. By changing the thickness of the scattering layer film in the photoanode, the quantum dots were adsorbed on TiO2 more effectively. By using the special ball-core structure, light was scattered so that the photoanode used the light many times, which effectively increased the efficiency of photoelectron production. After electrochemical testing of the device, it was found that the photoconversion efficiencies of the TiO2 transparent layer and the CeO2 scattering layer composite photoanode were greater than that of a single TiO2 photoanode without a scattering layer. The results showed that when the thickness of the scattered layer was 10 ± 1 µm, the highest photoelectric conversion efficiency (PCE) was obtained, which was 20% higher than that seen with TiO2 alone.

The 223A>G polymorphism of the leptin receptor gene is associated with macroangiopathy in type 2 diabetes mellitus.

To determine whether leptin receptor (LEPR) 223A>G polymorphism has an effect on the plasma leptin levels and the macroangiopathic complications in type 2 diabetes mellitus (T2DM). The genotypes and allelic frequencies of the LEPR 223A>G were examined with polymerase chain reaction and restriction fragment length polymorphism in 301 patients with T2DM and 172 unrelated healthy subjects. The plasma concentrations of leptin were determined in all subjects. The mean plasma leptin levels in the T2DM group were significantly higher than that of controls and the plasma levels of leptin were higher in diabetic patients with macroangiopathy than in patients without macroangiopathy (P < 0.05). The genotype (GG, AG and AA) distribution of 223A>G polymorphism was 58.3, 32.5, and 9.2% in diabetic patients with macroangiopathy, 75.3, 22.1, and 2.6% in patients without macroangiopathy, and 70.3, 27.5, 2.2% in controls respectively, a significant difference was found between diabetic patients with and without macroangiopathy (P < 0.05). The frequency of the allele A was higher in patients with macroangiopathy than in patients without macroangiopathy (25.6 vs. 16.3%; P < 0.05). Moreover, the plasma leptin levels were markedly higher in patients with AA genotype than those with AG or GG genotype in patients with macroangiopathy (P < 0.05). The LEPR 223A>G gene polymorphism associated with a predisposition to increased plasma leptin levels could constitute a useful predictive marker for diabetic macroangiopathy.

Comparison of cardioprotective efficacy resulting from a combination of atorvastatin and ischaemic post-conditioning in diabetic and non-diabetic rats.

The aim of the present study was to investigate whether the combination of acute or chronic atorvastatin treatment with ischaemic post-conditioning (IPost) exerts differential effects within the hearts of diabetic and non-diabetic rats. Diabetic and non-diabetic rats were randomly assigned to one of six groups: (i) a non-conditioned group; (ii) a group subjected to IPost; (iii) acute statin treatment (50 µmol/L atorvastatin during reperfusion) without IPost; (iv) acute statin treatment plus IPost; (v) chronic statin treatment (10 mg/kg atorvastatin per day for 2 weeks) without IPost; and (vi) chronic statin treatment plus IPost. The hearts from rats in each group were subjected to 30 min global ischaemia, followed by 120 min reperfusion. Infarct size, haemodynamics and Akt and endothelial nitric oxide synthase (eNOS) expression were examined. In hearts from diabetic rats, IPost did not limit infarct size or recover contractile dysfunction. Acute atorvastatin treatment with IPost limited infarct size and recovered contractile dysfunction in hearts from both diabetic and non-diabetic rats and further activated Akt and eNOS signalling pathways to enhance these protective effects in hearts from diabetic rats. Chronic statin treatment with IPost neither reduced infarct size nor increased recovery of myocardial dysfunction in hearts from both diabetic and non-diabetic rats; this may be associated with inhibition of Akt and eNOS phosphorylation. The combination of acute atorvastatin treatment with IPost had a greater protective effect within hearts from diabetic rats, but chronic statin treatment with IPost failed to protect against reperfusion injury in hearts from either diabetic or non-diabetic rats. These findings will be important for the design of future clinical investigations.

Massive data clustering by multi-scale psychological observations.

Clustering is the discovery of latent group structure in data and is a fundamental problem in artificial intelligence, and a vital procedure in data-driven scientific research over all disciplines. Yet, existing methods have various limitations, especially weak cognitive interpretability and poor computational scalability, when it comes to clustering massive datasets that are increasingly available in all domains. Here, by simulating the multi-scale cognitive observation process of humans, we design a scalable algorithm to detect clusters hierarchically hidden in massive datasets. The observation scale changes, following the Weber-Fechner law to capture the gradually emerging meaningful grouping structure. We validated our approach in real datasets with up to a billion records and 2000 dimensions, including taxi trajectories, single-cell gene expressions, face images, computer logs and audios. Our approach outperformed popular methods in usability, efficiency, effectiveness and robustness across different domains.

Effects of high thoracic epidural anesthesia on atrial electrophysiological characteristics and sympathetic nerve sprouting in a canine model of atrial fibrillation.

High thoracic epidural anesthesia (HTEA) blocks the afferent and efferent cardiac sympathetic nerve fibers and may affect atrial electrophysiological characteristics and nerve sprouting in patients with atrial fibrillation (AF). In this study, 18 dogs were randomly divided into a control group (n = 6), in which dogs were atrially paced at 400 beats/min for 6 weeks; an HTEA group (n = 6), in which dogs underwent atrial pacing and HTEA for 6 weeks; and a sham-operated group (n = 6), in which dogs underwent the operation but did not receive atrial pacing or HTEA. Electrophysiological examinations were performed in all groups. Cardiac nerves were immunocytochemically stained with anti-growth-associated protein 43 (GAP43) and anti-tyrosine hydroxylase (TH) antibodies. The protein expressions of nerve growth factor (NGF), GAP43 and TH in atrial myocardium were also studied by western blot. In addition, the plasma levels of C-reactive protein (CRP) and norepinephrine, as well as atrial production of superoxide anion (O(2)(·-)) and malondialdehyde, were measured. In the HTEA group, atrial effective refractory period increased (P < 0.05) and AF maintenance decreased (P < 0.01) significantly compared with the control group. The densities of GAP43-positive nerves and TH-positive nerves were significantly lower in the HTEA group compared with the control group. The protein levels of NGF, GAP43 and TH were also lower in the HTEA group compared with the control group. A significant positive correlation between the expressions of NGF and GAP43 (P < 0.01) was observed. A similar correlation was demonstrated for NGF and TH (P < 0.01) in our study. Furthermore, the plasma levels of CRP and norepinephrine, as well as the amount of O(2)(·-) and malondialdehyde produced from myocardium, decreased in the HTEA group compared with the control group. In conclusion, HTEA inhibited electrical and nerve remodeling and reduced the maintenance of AF in a canine AF model, in which process HTEA exhibited anti-inflammatory and antioxidant effects, indicating that, in addition to the efferent cardiac sympathetic nerve, afferent fibers also play an important role in the initiation and/or maintenance of AF.

Mechanisms mediating the cardioprotective effects of rapamycin in ischaemia-reperfusion injury.

1. In the present study, the temporal and concentration-dependent cardioprotective effects of rapamycin against ischaemia-reperfusion (I/R) injury, as well as the underlying mechanisms, were investigated. 2. Rat Langendorff-perfused isolated hearts were exposed to 40 min global ischaemia followed by 120 min reperfusion. Hearts were perfused with different concentrations of rapamycin before and after ischaemia. Myocardial injury was assessed in terms of infarct size and the release of lactate dehydrogenase (LDH) and creatine kinase (CK). The phosphorylation of Akt, extracellular signal-regulated kinase (ERK) 1/2 and endothelial nitric oxide synthase (eNOS) was determined at the end of reperfusion. 3. When administered prior to ischaemia, 25, 50 and 100 nmol/L rapamycin significantly reduced infarct size compared with control (40.1 ± 1.5, 26.3 ± 4.1 and 21.2 ± 3.4 vs 52.5 ± 4.5%, respectively) without affecting the recovery of ventricular function. No reduction in infarct size was observed when 50 nmol/L rapamycin was administered 10 or 120 min into the reperfusion period. 4. Rapamycin (50 nmol/L) enhanced the phosphorylation of Akt kinase but did not affect the phosphorylation of ERK1/2 or eNOS at the end of reperfusion. The cardioprotective effect of rapamycin was blocked by the phosphatidylinositol 3-kinase (Akt) inhibitor LY294002 (15 nmol/L). 5. In conclusion, rapamycin mediates cardioprotection prior to ischaemia and after reperfusion. This protection may involve activation of the phosphatidylinositol 3-kinase pathway.

Protective effects of isorhynchophylline on cardiac arrhythmias in rats and guinea pigs.

As one important constituent extracted from a traditional Chinese medicine, Uncaria Rhynchophylla Miq Jacks, isorhynchophylline has been used to treat hypertension, epilepsy, headache, and other illnesses. Whether isorhynchophylline protects hearts against cardiac arrhythmias is still incompletely investigated. This study was therefore aimed to examine the preventive effects of isorhynchophylline on heart arrhythmias in guinea pigs and rats and then explore their electrophysiological mechanisms. In vivo, ouabain and calcium chloride were used to establish experimental arrhythmic models in guinea pigs and rats. In vitro, the whole-cell patch-lamp technique was used to study the effect of isorhynchophylline on action potential duration and calcium channels in acutely isolated guinea pig and rat cardiomyocytes. The dose of ouabain required to induce cardiac arrhythmias was much larger in guinea pigs administered with isorhynchophylline. Additionally, the onset time of cardiac arrhythmias induced by calcium chloride was prolonged, and the duration was shortened in rats pretreated with isorhynchophylline. The further study showed that isorhynchophylline could significantly decrease action potential duration and inhibit calcium currents in isolated guinea pig and rat cardiomyocytes in a dose-dependent manner. In summary, isorhynchophylline played a remarkably preventive role in cardiac arrhythmias through the inhibition of calcium currents in rats and guinea pigs.

N6-Methyladenosine Methyltransferase METTL3 Promotes Angiogenesis and Atherosclerosis by Upregulating the JAK2/STAT3 Pathway via m6A Reader IGF2BP1.

Atherosclerosis (AS) is a life-threatening vascular disease. RNA N6-methyladenosine (m6A) modification level is dysregulated in multiple pathophysiologic processes including AS. In this text, the roles and molecular mechanisms of m6A writer METTL3 in AS progression were explored in vitro and in vivo. In the present study, cell proliferative, migratory, and tube formation capacities were assessed through CCK-8, Transwell migration, and tube formation assays, respectively. RNA m6A level was examined through a commercial kit. RNA and protein levels of genes were measured through RT-qPCR and western blot assays, respectively. VEGF secretion level was tested through ELISA assay. JAK2 mRNA stability was detected through actinomycin D assay. The relationship of METTL3, IGF2BP1, and JAK2 was investigated through bioinformatics analysis, MeRIP, RIP, RNA pull-down, and luciferase reporter assays. An AS mouse model was established to examine the effect of METTL3 knockdown on AS development in vivo. The angiogenetic activity was examined through chick chorioallantoic membrane assay in vivo. The results showed that METTL3 was highly expressed in ox-LDL-induced dysregulated HUVECs. METTL3 knockdown inhibited cell proliferation, migration, tube formation, and VEGF expression/secretion in ox-LDL-treated HUVECs, hampered AS process in vivo, and prevented in vivo angiogenesis of developing embryos. METTL3 positively regulated JAK2 expression and JAK2/STAT3 pathway in an m6A dependent manner in HUVECs. IGF2BP1 positively regulated JAK2 expression through directly binding to an m6A site within JAK2 mRNA in HUVECs. METTL3 knockdown weakened the interaction of JAK2 and IGF2BP1. METTL3 exerted its functions through JAK2/STAT3 pathway. In conclusion, METTL3 knockdown prevented AS progression by inhibiting JAK2/STAT3 pathway via IGF2BP1.

Rapamycin protects heart from ischemia/reperfusion injury independent of autophagy by activating PI3 kinase-Akt pathway and mitochondria K(ATP) channel.

OBJECTIVES: The purpose of this study was to investigate potential roles of rapamycin, a macrocytic lactone produced by Streptomyces hygroscopicus, in myocardial ischemia/reperfusion (I/R) injury. METHODS: Male Wistar rats were pretreated with three different doses of rapamycin (0.25, 2, and 5 mg/kg). Then, isolated rat hearts were exposed to 40 min of global ischemia followed by 120 min of reperfusion using a Langendorff apparatus. Western blot analysis was used to examine changes in the expression levels of ERK1/2 and Akt kinases and LC3 -II/I (a marker of autophagy). The area of myocardial infarction and cardiac function were evaluated. RESULTS: Our results demonstrated that rapamycin mediates cardioprotection in a dose-dependent manner in isolated rat hearts during myocardial I/R injury. Significant a autophagy was induced by rapamycin during I/R. Both, the mitochondrial K(ATP)-channel blocker 5-hydroxydecanoate (5-HD) and the PI3K inhibitor LY294002 (LY) abolished the protection afforded by rapamycin completely, while the inhibitors alone did not influence the infarct size in control hearts. However, the ERK1/2 inhibitor PD98059(PD) and the blocker of autophagy 3-methyladenine (3-MA) had no effect on rapamycin-mediated cardioprtection. CONCLUSIONS: Cardioprotection afforded by rapamycin involves the PI3K pathway and the activation of mitochondrial K(ATP)-channels, but is independent of rapamycin-induced autophagy. This study may have significant impact on clinical practice.

[The effect of carvedilol on coronary flow reserve in patients with dilated cardiomyopathy].

OBJECTIVE: To investigate the change of coronary flow reserve (CFR) in patients with dilated cardiomyopathy (DCM) with non-invasive transthoracic stress echocardiography before and after administration of carvedilol. METHODS: Seventy-five patients with DCM were included and divided into a group with heart failure (HF), a group without (non HF) and 30 healthy subjects with normal angiography and negative ECG exercise test were served as controls. In addition to traditional treatment, all patients were given enough carvedilol in 6 months. Doppler measurement of distal left anterior descending was recorded at rest and hyperemic state after adenosine infusion and CFR was calculated before and after the treatment. RESULTS: Compared with the controls, HF group and non HF group had greater left atrial diameter (LAd) and left ventricular diastolic diameter (LVDd) but less left ventricular ejection fraction (LVEF) and E/A than the controls before treatment (P < 0.05). LAd, LVDd and LVEF of the HF group and non HF group improved after treatment and there was significant difference of these indexes between the two groups (P < 0.05). Compared with the controls, HF group and non HF group had lower CFR before treatment (2.35 +/- 0.28 vs 2.57 +/- 0.31 vs 3.20 +/- 0.29, P < 0.05). After treatment with carvedilol, CFR rised in these two groups. Although CFR was still lower in the HF group than that in the control group (2.68 +/- 0.30 vs 3.20 +/- 0.29, P < 0.05), there was no difference between the non HF group and the controls (3.13 +/- 0.36 vs 3.20 +/- 0.29, P > 0.05). CONCLUSIONS: CFR decreased in patients with DCM and patients with heart failure had lower CFR than those without. Carvedilol could not only reverse the ventricular remodeling due to DCM, but also improve CFR in those patients. Detection of CFR with stress echocardiography could evaluate the effect of carvedilol earlier than the index of traditional echocardiography.

[Outcome of patients with ST-elevation myocardial infarction complicated by pre-hospital cardiac arrest underwent emergency percutaneous coronary intervention].

OBJECTIVE: To evaluate the outcome of ST-elevation acute myocardial infarction (STEMI) patients complicated pre-hospital cardiac arrest underwent percutaneous coronary intervention (PCI). METHODS: From September 2004 to November 2008, 1446 consecutive patients with acute STEMI underwent PCI in our department. 49 out of 1446 patients complicated by pre-hospital cardiac arrest. Clinical outcome including total mortality, adverse cardiac events, stroke and bleeding events during the hospitalization period and within 1 year after discharge was compared between patients with or without pre-hospital cardiac arrest. RESULTS: PCI success rate was similar (85.7% vs. 88.8%, P = 0.497) while the incidence of in-hospital cardiogenic shock 22.4% vs. 3.0%, P < 0.001 and cardiac arrest (44.9% vs. 5.9%, P < 0.001) and in-hospital mortality (36.7% vs. 2.0%, P < 0.001) were significantly higher in patients with pre-hospital cardiac arrest than patients without pre-hospital cardiac arrest. Time from symptom onset to emergency treatment, asystole as initial rhythm, Glasgow coma scale (GCS ≤ 7) and cardiogenic shock on admission were independent risk factors of in-hospital death in patients with pre-hospital cardiac arrest. During follow up, incidences of overall mortality, re-infarction, revascularization and stroke were similar between the two groups. CONCLUSIONS: STEMI patients with pre-hospital cardiac arrest undergoing emergency PCI are facing higher risk of cardiogenic shock and cardiac arrest and higher in-hospital mortality compared to those without pre-hospital cardiac arrest. However, the post-hospital discharge outcome was similar between the two groups.

[Atorvastatin use and coronary flow reserve in patients with coronary slow flow].

OBJECTIVE: To investigate the impact of statin use on coronary flow reserve (CFR) in patients with slow coronary flow. METHODS: A total of 91 patients with chest pain and coronary slow flow but normal coronary angiography were included in this study, patients were divided into statin group (atorvastatin 20 mg/d for 8 weeks, n = 51) and non-statin group (n = 40), 26 healthy subjects with normal angiography and negative exercise ECG test served as normal controls. Blood cholesterol was measured. Doppler coronary flow velocity and Doppler reserve measurement of distal left anterior descending were recorded at rest and adenosine infusion (140 microgxkg(-1)xmin(-1)) induced hyperemia state, CFR was calculated by the ratio of maximal hyperemia and baseline peak diastolic coronary flow velocity (hCFV and bCFV) before and after atorvastatin treatment. RESULTS: (1) Eight weeks later, total cholesterol and LDL-C levels were significantly lower in statin group than in non-statin group and control group [TC (3.83 +/- 0.80) mmol/L vs. (5.30 +/- 1.18) mmol/L vs. (5.32 +/- 1.17) mmol/L, P < 0.05; LDL-C (2.26 +/- 0.64) mmol/L vs. (3.28 +/- 0.85) mmol/L vs. (3.30 +/- 0.82) mmol/L, P < 0.05]. (2)Baseline CFR levels were significantly lower in statin group and non-statin group than that in control group (2.32 +/- 0.30 vs. 2.25 +/- 0.33 vs. 3.15 +/- 0.34, P < 0.05). Compared with non-statin group and statin group before treatment, 8 weeks statin treatment was associated with reduced bCFV [(26.06 +/- 3.22) cm/s vs. (29.02 +/- 3.36) cm/s and (26.06 +/- 3.22) cm/s vs. (28.43 +/- 3.40) cm/s, P < 0.05], increased hCFV [(77.63 +/- 8.96) cm/s vs. (65.17 +/- 7.22) cm/s and (77.63 +/- 8.96) cm/s vs. (64.58 +/- 6.26) cm/s, P < 0.05] and increased CFR (3.07 +/- 0.29 vs. 2.28 +/- 0.35 and 3.07 +/- 0.29 vs. 2.32 +/- 0.30, P < 0.05). bCFV, hCFV and CFR of statin group post treatment were similar to those of controls (P > 0.05). CONCLUSION: Patients with coronary slow flow were associated with lower CFR which could be significantly improved by statin therapy.