Performance of Subcutaneous Implantable Cardioverter Defibrillator (S-ICD) in Chinese Population with Primary Prevention Indications: A Prospective Observational Cohort Study.

BACKGROUND International studies have shown that use of a subcutaneous implantable cardioverter defibrillator (S-ICD) could reduce lead-related complications while maintaining adequate defibrillation performance; however, data from the Chinese population or other Asian groups are limited. MATERIAL AND METHODS SCOPE is a prospective, multicenter, observational cohort study. Two hundred patients with primary prevention indication for sudden cardiac death (SCD), who are candidates for S-ICD, will be enrolled. From the same population, another 200 patients who are candidates for transvenous implantable cardioverter defibrillator (TV-ICD) will be enrolled after being matched for age, sex, SCD high-risk etiology (ischemic cardiomyopathy, and non-ischemic cardiomyopathy, ion channel disease, and other) and atrial fibrillation in a 1: 1 ratio with enrolled S-ICD patients. All the patients will be followed for 18 months under standard of care. RESULTS The primary endpoint is proportion of patients free from inappropriate shock (IAS) at 18 months in the S-ICD group. The lower 95% confidence bound of the proportion will be compared with a performance goal of 90.3%, which was derived from the previous meta-analysis. The comparisons between S-ICD and TV-ICD on IAS, appropriate shock, and complications will be used as secondary endpoints without formal assumptions. CONCLUSIONS This is the first prospective multicenter study focusing on the long-term performance of S-ICD in a Chinese population. By comparing with the data derived from international historical studies and a matched TV-ICD group, data from SCOPE will allow for the assessment of S-ICD in the Chinese population in a contemporary real-world implantation level and programming techniques, which will help us to further modify the device implantation and programming protocol in this specific population in the future.

Facile fabrication of 3D Janus foams of electrospun cellulose nanofibers/rGO for high efficiency solar interface evaporation.

Solar-powered interfacial evaporation is one of the most efficient state-of-the-art technologies for producing clean water via desalination. Herein, we report a novel bio-based nanofibrous foam for high efficiency solar interface evaporation. To this end, a hybrid membrane of cellulose nanofibers/graphene oxide (GO) is first fabricated by electrospinning coupled with in situ layer-by-layer self-assembly technique. After that, the membrane is subjected to a foaming process in an aqueous NaBH4, which effectively transforms the 2D membrane into a 3D foam. This structure can improve the photothermal conversion efficiency and also facilitate the water transport at the gas-water interface. In the meantime, the GO is converted to the reduced GO (rGO) with a higher light absorption efficiency. Finally, one side of the foam is hydrophobically modified via spray-coating with a fluorocarbon resin (FR) to obtain the Janus type 3D foam, namely FR@EC/rGO. The resultant 3D foam combines the functions of solar energy absorption in the upper layer and water pumping capability in the lower layer. It exhibits an extraordinary solar vapor conversion efficiency of 94.2 % and a fast evaporation rate of 1.83 kg m-2 h-1, showing high potential in future seawater desalination.

Erchen decoction to reduce oxidative stress in dyslipidemia phlegm-dampness retention syndrome mice: In vivo mechanism revealed by metabolomics (liquid chromatography-mass spectrometry).

OBJECTIVE: Erchen decoction, a traditional Chinese medicine formula, can reduce the level of oxidative stress for the treatment of dyslipidemia phlegm-dampness retention syndrome (DPDRS); however, studies have not elucidated the mechanism underlying its metabolic action. Here, liquid chromatography-mass spectrometry (LC-MS)-based metabolomic techniques were utilized to characterize the in vivo effects of Erchen decoction in achieving reduction of oxidative stress levels and understand the potential metabolic mechanisms of action. METHODS: We constructed a DPDRS animal model using a multifactorial composite modeling approach, and Erchen decoction was administered by gavage. We employed LC-MS-based metabolomic techniques in combination with serum-associated factors, gene transcription, methylation detection, and hematoxylin and eosin staining. RESULTS: In this study, the constructed animal model of DPDRS had satisfactory quality. Erchen decoction treatment reduced the levels of low-density lipoprotein cholesterol, t total cholesterol and riglyceride; it improved the endothelial structure, increased levels of serum ß-nicotinamide adenine dinucleotide phosphate and glutathione concentrations, increased aortic phosphoserine aminotransferase and phosphoserine phosphatase gene expression levels, and decreased aortic phosphoglycerate dehydrogenase methylation level. A total of 64 differential metabolites were obtained using LC-MS assay, and 34 differential metabolic pathways were obtained after enrichment. CONCLUSIONS: Erchen decoction treatment of DPDRS mice reversed lipid indexes, improved vascular endothelial structure, increased serum and aortic anti-oxidative stress factor concentration and expression levels, and decreased methylation levels, thereby reducing oxidative stress and protecting vascular endothelium. Tricarboxylic acid cycle and metabolic pathways of serum glutamine, serine, tryptophan, pyrimidine, and pyruvate were the most relevant metabolic pathways involved in reducing oxidative stress levels by Erchen decoction during DPDRS treatment; especially, mitochondrial redox homeostasis maintenance in endothelial cells may be crucial. In this work, the therapeutic potential of Erchen decoction for reducing the oxidative stress level in DPDRS was demonstrated; however, its in-depth mechanism is worth further exploration.

Facile fabrication of three-dimensional nanofibrous foams of cellulose@g-C3N4@Cu2O with superior visible-light photocatalytic performance.

In this work, a unique three-dimensional nanofibrous foam of cellulose@g-C3N4@Cu2O was prepared via electrospinning followed by a foaming process. A cellulose solution in DMAc/LiCl containing g-C3N4 and CuSO4 was applied for electrospinning, while aqueous alkali was used as the coagulation bath. The solidification of electrospun cellulose/g-C3N4 nanofibers would be accompanied with in-situ formation of Cu(OH)2 nanoparticles. Interestingly, the hydrogen gas (H2) generated from NaBH4 could transform the two-dimensional membrane into a three-dimensional foam, leading to the increased specific surface area and porosity of the material. Meanwhile, the Cu(OH)2 nanoparticles attached on the electrospun nanofibers were reduced to Cu2O to form a p-n heterostructure between Cu2O and g-C3N4. The as-prepared cellulose@g-C3N4@Cu2O foam exhibited a high degradation efficiency (99.5 %) for the dye of Congo Red under visible light radiation. And ·O2- was discovered to be the dominant reactive species responsive for dye degradation. Moreover, the cellulose@g-C3N4@Cu2O could maintain its initial degradation efficiency even after seven cycles of reuse, suggesting the excellent stability and cycling performance.

Mechanically Strong and Electrically Conductive Polyethylene Oxide/Few-Layer Graphene/Cellulose Nanofibrils Nanocomposite Films.

In this work, a cellulose nanofibrils (CNFs)/few-layer graphene (FLG) hybrid is mechanically stripped from bamboo pulp and expanded graphene (EG) using a grinder. This strategy is scalable and environmentally friendly for high-efficiency exfoliation and dispersion of graphene in an aqueous medium. The in situ-generated CNFs play a key role in this process, acting as a "green" dispersant. Next, the obtained CNFs-FLG is used as a functional filler in a polyoxyethylene (PEO) matrix. When the composition of CNFs-FLG is 50 wt.%, the resultant PEO/CNFs-FLG nanocomposite film exhibits a Young's modulus of 1.8 GPa and a tensile strength of 25.7 MPa, showing 480% and 260% enhancement as compared to those of the pure PEO film, respectively. Remarkably, the incorporation of CNFs-FLG also provides the nanocomposite films with a stunning electrical conductivity (72.6 S/m). These attractive features make PEO/CNFs-FLG nanocomposite films a promising candidate for future electronic devices.

Polyethylenimine-Functionalized Nanofiber Nonwovens Electrospun from Cotton Cellulose for Wound Dressing with High Drug Loading and Sustained Release Properties.

Electrospun cellulose nanofiber nonwovens have shown promise in wound dressing owing to the highly interconnected pore structure, high hydrophilicity coupled with other coveted characteristics of biodegradability, biocompatibility and renewability. However, electrospun cellulose wound dressings with loaded drugs for better wound healing have been rarely reported. In this study, a novel wound dressing with a high drug loading capacity and sustained drug release properties was successfully fabricated via electropinning of cellulose followed by polyethylenimine (PEI)-functionalization. Remarkably, the grafted PEI chains on the surface of electrospun cellulose nanofibers provided numerous active amino groups, while the highly porous structure of nonwovens could be well retained after modification, which resulted in enhanced adsorption performance against the anionic drug of sodium salicylate (NaSA). More specifically, when immersed in 100 mg/L NaSA solution for 24 h, the as-prepared cellulose-PEI nonwoven displayed a multilayer adsorption behavior. And at the optimal pH of 3, a high drug loading capacity of 78 mg/g could be achieved, which was 20 times higher than that of pristine electrospun cellulose nonwoven. Furthermore, it was discovered that the NaSA-loaded cellulose-PEI could continuously release the drug for 12 h in simulated body fluid (SBF), indicating the versatility of cellulose-PEI as an advanced wound dressing with drug carrier functionalities.

One-pot superhydrophilic surface modification of waste polyurethane foams for high-efficiency oil/water separation.

Despite of the fact that polymers have brought tremendous convenience to human life, they have also inevitably caused considerable environmental pollution after their service life. Therefore, a feasible strategy that can effectively recycle waste polymers and endow them with high added value is much desired. Superwetting materials have shown great promise in oily wastewater treatment because of their high oil/water separation efficiency. However, most of these materials present some limitations, such as complex preparation procedures and poor salt tolerance, which hamper their practical applications. In this study, an iron hydroxide@polydopamine@waste polyurethane foam (Fe(OH)3@PDA@WPU) was synthesized via a facile and mild "one-pot" reaction. During this process, polymerization of dopamine and in situ growth of Fe(OH)3 were simultaneously realized, and the resultant PDA and Fe(OH)3 nanoparticles were firmly attached to the surface of WPU. Due to the abundant hydrophilic groups from PDA and Fe(OH)3 coupled with the surface roughness created by Fe(OH)3 nanoparticles, the surface properties of the foam could be changed from hydrophobic to superhydrophilic. Remarkably, the Fe(OH)3@PDA@WPU was capable of separating various oil/water mixtures even under some severe conditions (e.g. erosion in a saturated sodium chloride solution and longtime sonication), demonstrating high potential in marine oily sewage treatment. Moreover, this work also paved a new path for reducing the negative impact of waste polymer foams on our environment, and in the meantime realizing their high value utilization.

Effects of Erchen Decoction on Oxidative Stress-Related Cytochrome P450 Metabolites of Arachidonic Acid in Dyslipidemic Mice with Phlegm-Dampness Retention Syndrome: A Randomized, Controlled Trial on the Correspondence between Prescription and Syndrome.

Phlegm-dampness retention (PDR) syndrome is one of the main syndromes of dyslipidemia. This study investigated the effects of Erchen decoction (ECD) on concentrations of two oxidative stress-related cytochrome P450 (CYP450) metabolites of arachidonic acid-14,15-dihydroxyeicosatrienoic acid (14,15-DHET) and 20-hydroxyeicosatetraenoic acid (20-HETE)-in mice with dyslipidemia and phlegm-dampness retention (PDR) syndrome (n = 5 C57BL/6J mice and n = 30 apolipoprotein E knockout mice). Murine models of the disease and syndrome were established using multifactor stimulation. Then, all mice were assigned to normal, model, low- (L-), medium- (M-), or high- (H-) dose ECD groups or to a control or an unmatched prescription-syndrome (unmatched P-S) group; five mice were included in each group. Dose formulations were administered by oral gavage for 30 days to animals in the corresponding groups. We detected and analyzed hematoxylin and eosin (HE) staining characteristics of the mouse aorta and serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), peroxynitrite (ONOO-), 14,15-DHET, and 20-HETE concentrations in each group. TC and LDL-C concentrations significantly decreased in the M-ECD versus control group (P < 0.05); however, the TC and LDL-C concentrations were not significantly different in the unmatched P-S versus model group (P > 0.05). After treatment in the P-S correspondence groups (L-ECD, M-ECD, and H-ECD groups), the concentration of ONOO- decreased to different degrees in each group. Among these groups, the concentration of ONOO- significantly decreased in the L-ECD, M-ECD, and H-ECD groups versus the model group (P < 0.05). However, the concentration of ONOO- was not significantly different in the unmatched P-S versus the model group (P > 0.05). From the perspective of aortic HE staining, the P-S group experienced an improved endothelium structure after treatment. 14,15-DHET concentrations significantly increased in the normal, M-ECD, and H-ECD groups versus the model group; in the H-ECD versus the L-ECD group; and in the H-ECD versus the control group (all P < 0.05) to various extents after different doses of the prescription. 20-HETE concentrations pronouncedly decreased in the M-ECD versus normal group; in the M- and H-ECD groups versus the model group; in the M-ECD versus the L-ECD group; in the M-ECD versus the control group; and in the M-ECD versus the unmatched P-S (P < 0.05). However, the concentrations of 14,15-DHET and 20-HETE in the model group were not significantly different from those of the unmatched P-S (P > 0.05). In this study, ECD reversed blood lipid indexes and ameliorated oxidative stress-related metabolites, elevating serum 14,15-DHET and lowering serum 20-HETE in mice with dyslipidemia and PDR syndrome via CYP450 pathways of arachidonic acid metabolism. The efficacy of ECD relies on correspondence between the prescription and the syndrome. These findings scientifically validate the treatment according to traditional Chinese medicine syndrome differentiation. ECD can strengthen the protective effect on the vascular endothelium by driving out pathogenic factors and strengthening healthy resistance. Its efficacy may be related to the adjustment of the polarization state of macrophages.

Iron-Loaded Carbon Aerogels Derived from Bamboo Cellulose Fibers as Efficient Adsorbents for Cr(VI) Removal.

A unique iron/carbon aerogel (Fe/CA) was prepared via pyrolysis using ferric nitrate and bamboo cellulose fibers as the precursors, which could be used for high-efficiency removal of toxic Cr(VI) from wastewaters. Its composition and crystalline structures were characterized by FTIR, XPS, and XRD. In SEM images, the aerogel was highly porous with abundant interconnected pores, and its carbon-fiber skeleton was evenly covered by iron particles. Such structures greatly promoted both adsorption and redox reaction of Cr(VI) and endowed Fe/CA with a superb adsorption capacity of Cr(VI) (182 mg/g) with a fast adsorption rate (only 8 min to reach adsorption equilibrium), which outperformed many other adsorbents. Furthermore, the adsorption kinetics and isotherms were also investigated. The experiment data could be much better fitted by the pseudo-second-order kinetics model with a high correlating coefficient, suggesting that the Cr(VI) adsorption of Fe/CA was a chemical adsorption process. Meanwhile, the Langmuir model was found to better describe the isotherm curves, which implied the possible monolayer adsorption mechanism. It is noteworthy that the aerogel adsorbent as a bulk material could be easily separated from the water after adsorption, showing high potential in real-world water treatment.

Study on the Effect of Macrophages on Vascular Endothelium in Mice With Different TCM Syndromes of Dyslipidemia and its Biological Basis Based on RNA-Seq Technology.

Background: "Treating the same disease with different methods" is a Traditional Chinese medicine (TCM) therapeutic concept suggesting that, while patients may be diagnosed with the same disease, they may also have different syndromes that require distinct drug administrations. Objective: This study aimed to identify the differentially expressed genes and related biological processes in dyslipidemia in relation to phlegm-dampness retention (PDR) syndrome and spleen and kidney Yang deficiency (SKYD) syndrome using transcriptomic analysis. Methods: Ten ApoE-/- mice were used for the establishment of dyslipidemic disease-syndrome models via multifactor-hybrid modeling, with five in the PDR group and five in the SKYD group. Additionally, five C57BL/6J mice were employed as a normal control group. Test model-quality aortic endothelial macrophages in mice were screened using flow cytometry. Transcriptomic analysis was performed for macrophages using RNA-Seq. Results: A quality assessment of the disease-syndrome model showed that levels of lipids significantly increased in the PDR and SKYD groups, compared to the normal control group, p < 0.05. Applying, in addition, hematoxylin and eosin staining of aorta, the disease model was also successfully established. A quality assessment of the syndrome models showed that mice in the PDR group presented with typical manifestations of PDR syndrome, and mice in the SKYD group had related manifestations of SKYD syndrome, indicating that the syndrome models were successfully constructed as well. After comparing the differentially expressed gene expressions in macrophages of the dyslipidemic mice with different syndromes, 4,142 genes were identified with statistical significance, p < 0.05. Gene ontology analysis for the differentially expressed genes showed that the biological process of difference between the PDR group and the SKYD group included both adverse and protective processes. Conclusion: The differentially expressed genes between PDR syndrome and SKYD syndrome indicate different biological mechanisms between the onsets of the two syndromes. They have distinctive biological processes, including adverse and protective processes that correspond to the invasion of pathogenic factors into the body and the fight of healthy Qi against pathogenic factors, respectively, according to TCM theory. Our results provide biological evidence for the TCM principle of "treating the same disease with different treatments."

A new method to recommend left ventricular lead positions for improved CRT volumetric response and long-term prognosis.

OBJECTIVES: Using ECG-gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), we sought to develop and validate a new method to recommend left ventricular (LV) lead positions in order to improve volumetric response and long-term prognosis after cardiac resynchronization therapy (CRT). METHODS: Seventy-nine patients received gated SPECT MPI at baseline, and echocardiography at baseline and follow-up. The volumetric response referred to a reduction of ≥ 15% in LV end-systolic volume 6 months after CRT. After excluding apical, septal, and scarred segments, there were three levels of recommended segments: (1) the optimal recommendation: the latest contracting viable segment; (2) the 2nd recommendation: the late contracting viable segments whose contraction delays were within 10° of the optimal recommendation; and (3) the 3rd recommendation: the viable segments adjacent to the optimal recommendation when there was no late contracting viable segment. RESULTS: After excluding 11 patients whose LV lead was placed in apical or scarred segments, 75.6% of the patients concordant to recommended LV segments (n = 41) responded to CRT while 51.9% of those with non-recommended LV lead locations (n = 27) were responders (P = .043). Response rates were 76.9%, 76.9% , and 73.3% (P = .967), respectively, when LV lead was implanted in the optimal recommendation (n = 13), the 2nd recommendation (n = 13), and the 3rd recommendation (n = 15). LV leads placed at recommended segments reduced composite events of all-cause mortality or heart failure (HF) rehospitalization compared with pacing at non-recommended segments (log-rank χ2 = 5.623, P = .018). CONCLUSIONS: Pacing in the recommended LV lead segments identified on gated SPECT MPI was associated with improved volumetric response to CRT and long-term prognosis.

Acquired long QT syndrome in chronic kidney disease patients.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in chronic kidney disease (CKD) patients. QT interval prolongation is a congenital or acquired condition that is associated with an increased risk of torsade de pointes (TdP), sudden cardiac death (SCD), and all-cause mortality in the general population. The prevalence of acquired long QT syndrome (aLQTS) is high, and various acquired conditions contribute to the prolonged QT interval in patients with CKD. More notably, the prolonged QT interval in CKD is an independent risk factor for SCD and all-cause mortality. In this review, we focus on the epidemiological characteristics, risk factors, underlying mechanisms and treatments of aLQTS in CKD, promoting the management of aLQTS in CKD patients.

Serum metabolomics model and its metabolic characteristics in patients with different syndromes of dyslipidemia based on nuclear magnetic resonance.

Dyslipidemia is known as a common clinical disease that affects the health of millions of people around the world. The treatment of dyslipidemia with traditional Chinese medicine (TCM) is generally based on the accurate identification of disease syndromes. TCM syndromes are judged by traditional four-diagnosis method, which is subjective and fuzzy. Additionally, the judgment of TCM syndromes highly depend on doctors' own clinical experience. In this present study, we used nuclear magnetic resonance (NMR)-based serum metabolomics patterns to figure out the metabolic characteristics of different syndromes in patients with dyslipidemia. In total, we enrolled 60 patients with dyslipidemia (30 cases with Spleen and Kidney Yang Deficiency syndrome (SKYD) and 30 cases with Phlegm-Dampness Retention syndrome (PDR)) and 20 healthy controls. Based on NMR technique, the serum metabolomics patterns of patients with different syndromes and healthy controls were analyzed, in the hope of screening the different metabolites among different syndromes and the differential metabolic pathway, as well as exploring the changes of metabolic network among different syndromes of dyslipidemia. The results suggested that the serum metabolomics patterns based on NMR was used to identify serum metabolites in patients with dyslipidemia of SKYD and PDR as well as healthy controls. Besides, it was found that the metabolic patterns of these three groups can be distinguished well and the different metabolites between different syndromes can be screened. From the point of view of metabolites, the metabolic characteristics of the patients with PDR were mainly the accumulation of noxious metabolites, while the metabolic characteristics of the patients with SKYD were mainly the lack of metabolites with protective function. From the point of view of metabolic mode, there were different metabolic patterns in patients with different syndromes of dyslipidemia in liver metabolism, oxidation, inflammatory reaction as well as energy metabolism, which reflects the difference of syndromes from different angles. The differences in metabolic outcomes among patients with different syndromes of dyslipidemia had a close association with to the effects of multiple signaling pathways. This study identified the characteristics of serum metabolic model of patients with different syndromes of dyslipidemia and the potential differential metabolites and characteristic metabolic characteristics of syndromes in order to understand the biological characteristics of patients with dyslipidemia of SKYD and PDR.

Evaluation of the therapeutic effects of QuickOpt optimization in Chinese patients with chronic heart failure treated by cardiac resynchronization.

In this trial, long-term therapeutic effects and clinical improvements in Chinese chronic heart failure patients optimized by QuickOpt or echocardiography were compared for atrioventricular (AV) and interventricular (VV) delay optimizations after cardiac resynchronization therapy (CRT) with pacing (CRT-P) or with pacing and defibrillator (CRT-D) therapy. One hundred and ninety-six subjects (50%) had dilated cardiomyopathy, 108 (27.6%) had ischemic heart disease and 112 (28.6%) were hypertensive and were randomized into QuickOpt (198) or echocardiographic optimization (control) (194) groups at ≤2-weeks post-implantation. Programmed AV/VV delay was optimized at baseline and at 3 and 6 months. Left ventricular end-systolic volume (LVESV), New York Heart Association (NYHA) class, specific activity scale (SAS), and the six-minute walk tests (6MWT) were evaluated by blinded researchers at 12 months. Of the QuickOpt group, LVESV decreased significantly by 24.7% ± 33.9% compared with baseline, while LVESV of Controls decreased by 25.1% ± 36.1% (P = 0.924). NYHA class, SAS and 6MWT also improved similarly in both groups at 12 months. Mortality in both groups was not significantly different (11.0% vs 7.6%, P = 0.289). However, there was a significant difference in the time required for optimization by QuickOpt compared with echocardiography (3.33 ± 3.11 vs 58.79 ± 27.03 minutes, P < 0.000).

Synergistic Effect of Dofetilide and Mexiletine on Prevention of Atrial Fibrillation.

BACKGROUND: Although atrial fibrillation (AF) is the most common abnormal heart rhythm and its prevalence continues to rise, there is a marked paucity of effective and safe antiarrhythmic drugs for AF. This study was done to test whether combined use of dofetilide and mexiletine exhibits not only a synergistic effect on AF suppression but also a safer profile in drug-induced ventricular proarrhythmias. METHODS AND RESULTS: The effects of dofetilide plus mexiletine on atrial effective refractory period (ERP), AF inducibility, QT, and QT-related ventricular arrhythmias were studied using the isolated arterially perfused rabbit atrial and ventricular wedge preparations. Dofetilide or mexiletine alone mildly to moderately prolonged atrial ERP, but their combined use produced a markedly rate-dependent increase in atrial ERP. Dofetilide (3 nmol/L) plus mexiletine (10 µmol/L) increased the ERP by 28.2% from 72.2±5.7 to 92.8±5.9 ms (n=9, P<0.01) at a pacing rate of 0.5 Hz and by 94.5% from 91.7±5.2 to 178.3±12.0 ms (n=9, P<0.01) at 3.3 Hz. Dofetilide plus mexiletine strongly suppressed AF inducibility. On the other hand, dofetilide at 10 nmol/L produced marked QT and Tp-e prolongation, steeper QT-BCL and Tp-e-BCL slopes, and induced early afterdepolarizations and torsade de pointes in the ventricular wedges. Mexiletine at 10 µmol/L reduced dofetilide-induced QT and Tp-e prolongation, QT-BCL and Tp-e-BCL slopes, and abolished early afterdepolarizations and torsade de pointes. CONCLUSIONS: In rabbits, combined use of dofetilide and mexiletine not only synergistically increases atrial ERP and effectively suppresses AF inducibility, but also markedly reduces QT liability and torsade de pointes risk posed by dofetilide alone.

GABAergic Interneurons are Required for Generation of Slow CA1 Oscillation in Rat Hippocampus.

Neuronal oscillations are fundamental to hippocampal function. It has been shown that GABAergic interneurons make an important contribution to hippocampal oscillations, but the underlying mechanism is not well understood. Here, using whole-cell recording in the complete hippocampal formation isolated from rats at postnatal days 14-18, we showed that GABAA receptor-mediated activity enhanced the generation of slow CA1 oscillations. In vitro, slow oscillations (0.5-1.5 Hz) were generated in CA1 neurons, and they consisted primarily of excitatory rather than inhibitory membrane-potential changes. These oscillations were greatly reduced by blocking GABAA receptor-mediated activity with bicuculline and were enhanced by increasing such activity with midazolam, suggesting that interneurons are required for oscillation generation. Consistently, CA1 fast-spiking interneurons were found to generate action potentials usually preceding those in CA1 pyramidal cells. These findings indicate a GABAA receptor-based mechanism for the generation of the slow CA1 oscillation in the hippocampus.

Association of the hERG mutation with long-QT syndrome type 2, syncope and epilepsy.

Mutations in the human ether­à­go­go­related gene (hERG) are responsible for long­QT syndrome (LQTS) type 2 (LQT2). In the present study, a heterozygous missense mutation (A561V) linked to LQT2, syncope and epilepsy was identified in the S5/pore region of the hERG protein. The mutation, A561V, was prepared and subcloned into hERG­pcDNA3.0. Mutant plasmids were co­transfected into HEK­293 cells, which stably express wild­type (WT) hERG, in order to mimic a heterozygous genotype, and the whole­cell current was recorded using a patch­clamp technique. Confocal microscopy was performed to evaluate the membrane distribution of the hERG channel protein using a green fluorescent protein tagged to the N­terminus of hERG. A561V­hERG decreased the amplitude of the WT­hERG currents in a concentration­dependent manner. In addition, A561V­hERG resulted in alterations to activation, inactivation and recovery from inactivation in the hERG protein channels. Further evaluation of hERG membrane localization indicated that the A561V­hERG mutant protein was unable to travel to the plasma membrane, which resulted in a trafficking­deficient WT­hERG protein. In conclusion, A561V­hERG exerts a potent dominant­negative effect on WT­hERG channels, resulting in decreased hERG currents and impairment of hERG membrane localization. This may partially elucidate the clinical manifestations of LQTS patients who carry the A561V mutation.

Vasostatin-2 inhibits cell proliferation and adhesion in vascular smooth muscle cells, which are associated with the progression of atherosclerosis.

Recently, the serum expression level of vasostatin-2 was found to be reduced and is being studied as an important indicator to assess the presence and severity of coronary artery disease; the functional properties of vasostatin-2 and its relationship with the development of atherosclerosis remains unclear. In this study, we attempted to detect the expression of vasostatin-2 and its impact on human vascular smooth muscle cells (VSMCs). Quantitative real-time PCR (qRT-PCR) and western blot were used to assess the expression level of vasostatin-2 in VSMCs between those from atherosclerosis and disease-free donors; we found that vasostatin-2 was significantly down-regulated in atherosclerosis patient tissues and cell lines. In addition, the over-expression of vasostatin-2 apparently inhibits cell proliferation and migration in VSMCs. Gain-of-function in vitro experiments further show that vasostatin-2 over-expression significantly inhibits inflammatory cytokines release in VSMCs. In addition, cell adhesion experimental analysis showed that soluble adhesion molecules (sICAM-1, sVCAM-1) had decreased expression when vasostatin-2 was over-expressed in VSMCs. Therefore, our results indicate that vasostatin-2 is an atherosclerosis-related factor that can inhibit cell proliferation, inflammatory response and cell adhesion in VSMCs. Taken together, our results indicate that vasostatin-2 could serve as a potential diagnostic biomarker and therapeutic option for human atherosclerosis in the near future.