Association between baseline glycated hemoglobin level and atrial fibrillation recurrence following cryoballoon ablation among patients with and without diabetes.

OBJECTIVES: The study aims to assess the effect of baseline glycated hemoglobin (HbA1c) levels on atrial fibrillation (AF) recurrence following cryoballoon ablation in patients with and without diabetes. METHODS: Consecutive AF patients receiving first cryoballoon ablation between April 2018 and April 2021 were included. AF recurrence and other clinical outcomes were recorded for a minimum of 12 months post-ablation, with regular assessments at 3, 6, and 12 months, followed by annual check-ups. The primary outcome was AF recurrence after ablation at longest follow-up. Multivariate Cox proportional hazards regression models were utilized to calculate the hazard ratio (HR) and 95% CI per standard deviation (SD) increase of baseline HbA1c level. RESULTS: 335 patients were included in the analysis. The mean age was 61.7 years, 61.8% were male. 12.8% had type 2 diabetes, and 81.7% of patients had paroxysmal AF. The median level of HbA1c was 5.3%, and the mean CHA2DS2-VASc score was 1.8. All cryoballoon ablation procedures, utilizing a 28-mm balloon, achieved successful pulmonary vein isolation. Over a median follow-up of 18 months, 105 patients (31.3%) experienced AF recurrence. In multivariate Cox proportional hazards analysis, a higher HbA1c level, persistent AF (HR 1.91, 95% CI 1.08 to 3.39, P = 0.026), alcohol consumption (HR 2.67, 95% CI 1.33 to 5.37, P = 0.006), and Nadir RSPV (HR 1.04, 95% CI 1.00 to 1.08, P = 0.005) were significant predictors of AF recurrence. Per-SD increase of HbA1c was associated with a 1.75-fold increase risk of AF recurrence (HR 1.75, 95% CI 1.39 to 2.21, P < 0.001). Subgroup analysis revealed that a higher HbA1c level was associated with a higher risk of AF recurrence in patients with and without diabetes, and in patients with paroxysmal and persistent AF. CONCLUSION: Baseline HbA1c level was an independent predictor of AF recurrence following cryoablation, both in patients with and without diabetes.

Archaeal communities change responding to anthropogenic and natural treatments of freeze-thawed soils.

The coverage of accumulated snow plays a significant role in inducing changes in both microbial activity and environmental factors within freeze-thaw soil systems. This study aimed to analyze the impact of snow cover on the dynamics of archeal communities in freeze-thaw soil. Furthermore, it seeks to investigate the role of fertilization in freeze-thaw soil. Four treatments were established based on snow cover and fertilization:No snow and no fertilizer (CK-N), snow cover without fertilizer (X-N), fertilizer without snow cover (T-N), and both fertilizer and snow cover (T-X). The research findings indicated that after snow cover treatment, the carbon, nitrogen, and phosphorus content in freeze-thaw soil exhibit periodic fluctuations. Snow covered effectively altered the community composition of bacteria and archaea in the soil, with a greater impact on archaeal communities than on bacterial communities. Snow covered improves the stability of archaeal communities in freeze-thaw soil. Additionally, the arrival of snow also enhanced the correlation between archaea and environmental factors, with the key archaeal phyla involved being Nanoarchaeota and Crenarchaeota. Further research showed that the application of organic fertilizers also had some impact on freeze-thaw soil, but this impact was smaller compared to snow cover. In summary, the arrival of snow could alter the archaeal community and protect nutrient elements in freeze-thaw soil, reducing their loss, and its effect is more pronounced compared to the application of organic fertilizers.

Genome- and transcriptome-wide identification of trehalose-6-phosphate phosphatases (TPP) gene family and their expression patterns under abiotic stress and exogenous trehalose in soybean.

BACKGROUND: Trehalose-6-phosphate phosphatase (TPP) is an essential enzyme catalyzing trehalose synthesis, an important regulatory factor for plant development and stress response in higher plants. However, the TPP gene family in soybean has not been reported. RESULTS: A comprehensive analysis of the TPP gene family identified 18 GmTPPs classified into eight groups based on the phylogenetic relationships and the conservation of protein in six monocot and eudicot plants. The closely linked subfamilies had similar motifs and intron/exon numbers. Segmental duplication was the main driving force of soybean GmTPPs expansion. In addition, analysis of the cis-regulatory elements and promoter regions of GmTPPs revealed that GmTPPs regulated the response to several abiotic stresses. Moreover, RNA-seq and qRT-PCR analysis of the tissue-specific GmTPPs under different abiotic stresses revealed that most GmTPPs were associated with response to different stresses, including cold, drought, saline-alkali, and exogenous trehalose. Notably, exogenous trehalose treatment up-regulated the expression of most TPP genes under saline-alkali conditions while increasing the carbohydrate and trehalose levels and reducing reactive oxygen species (ROS) accumulation in soybean sprouts, especially in the saline-alkali tolerant genotype. Furthermore, the interaction network and miRNA target prediction revealed that GmTPPs interacted with abiotic stress response-related transcription factors. CONCLUSIONS: The findings in this study lay a foundation for further functional studies on TPP-based breeding to improve soybean development and stress tolerance.

Exogenous melatonin mitigates saline-alkali stress by decreasing DNA oxidative damage and enhancing photosynthetic carbon metabolism in soybean (Glycine max [L.] Merr.) leaves.

Saline-alkali stress (SS) is a common abiotic stress affecting crop cultivation worldwide, seriously inhibiting plant growth and biomass accumulation. Melatonin has been proven to relieve the inhibition of multiple abiotic stresses on plant growth. Therefore, soybean cultivars Heihe 49 (HH49, SS-tolerant) and Henong 95 (HN95, SS-sensitive) were pot-cultured in SS soil and then treated with 300 µM melatonin at the V1 stage, when the first trifoliate leaves were fully unfolded, to investigate if melatonin has an effect on SS. SS increased reactive oxygen species (ROS) accumulation in soybean leaves and thereby induced DNA oxidative damage. In addition, SS retarded cell growth and decreased the mesophyll cell size, chloroplast number, photosynthetic pigment content, which further reduced the light energy capture and electron transport rate in soybean leaves, and affected carbohydrate accumulation and metabolism. However, melatonin treatment reduced SS-induced ROS accumulation in the soybean leaves by increasing antioxidant content and oxidase activity. Effective removal of ROS reduced SS-induced DNA oxidative damage in the soybean leaf genome, which was represented by decreased random-amplified polymorphic DNA polymorphism, 8-hydroxy-20-deoxyguanine content, and relative density of apurinic/apyrimidinic-sites. Melatonin treatment also increased the volume of mesophyll cells, the numbers of chloroplast and starch grains, the contents of chlorophyll a and b and carotenoids in soybean seedling leaves treated with SS, thereby increasing the efficiency of effective light capture and electron transfer and improving photosynthesis. Subsequently, carbohydrate accumulation and metabolism in soybean leaves under SS were improved by melatonin treatment, which contributes to providing basic substances and energy for cell growth and metabolism, ultimately improving soybean SS tolerance.

Refractory ventricular tachycardia and heart failure due to anti-mitochondrial antibody-positive inflammatory myopathy.

BACKGROUND: Anti-mitochondrial antibody (AMA)-positive inflammatory myopathy, a rare type of idiopathic inflammatory myopathy which was frequently difficult to diagnose, can affect muscles and the structure and electrical conduction of the heart. Early identification and treatment of this myopathy can prevent serious cardiovascular adverse events and improve cardiac function. CASE PRESENTATION: We report a patient who experienced repeated syncope, ventricular tachycardia (VT) and heart failure accompanied by weakness and muscle atrophy. He was initially diagnosed with dilated cardiomyopathy and received implantable cardioverter-defibrillator therapy. He was subsequently misdiagnosed as muscular dystrophy due to progressive muscular atrophy. However, the patient developed repeated and refractory VT storms that were not alleviated by conventional therapy. Finally, he was diagnosed with AMA-positive inflammatory myopathy with cardiac injuries. The patient was markedly recovered by being treated with immunosuppressive and immunomodulatory therapy. CONCLUSION: AMA could be screened when discovering myopathies accompanied by unexplained cardiac symptoms. Our findings provide insights into the diagnosis and therapy of this rare and severe disease.

Long-term and Temporal Outcomes of Transcatheter Versus Surgical Aortic-valve Replacement in Severe Aortic Stenosis: A Meta-analysis.

OBJECTIVE: To determine the 5-year and temporal performance of TAVR versus SAVR. BACKGROUND: TAVR has become a valuable treatment for severe aortic stenosis but the long-term safety and efficacy remain unclear. METHODS: Databases were searched until October 6, 2019 for randomized trials with ≥5 years' follow-up. Primary outcome was all-cause mortality. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled with random-effects models. RESULTS: We included 4 trials with 3,758 patients. TAVR was associated with a significantly higher 5-year all-cause mortality than SAVR (OR, 1.19; 95% CI, 1.03-1.37; P = 0.02). Landmark analysis showed no significant difference within 2 years (OR, 0.92; 95% CI, 0.79-1.08; P = 0.33) but a statistically higher mortality in TAVR between 2 and 5 years (OR, 1.32; 95% CI, 1.14-1.52; P = 0.0002), with significant difference between these 2 temporal phases (P for interaction = 0.001). Similar interaction was found for cardiovascular mortality and several other outcomes. Rates of all-cause mortality or disabling stroke, permanent pacemaker implantation, aortic-valve rehospitalization, and reintervention were higher, but rates of major bleeding and new-onset fibrillation were lower in TAVR at 5 years. The incidences of myocardial infarction, stroke, and transient ischemic attack were not statistically different between TAVR and SAVR. CONCLUSIONS: TAVR was associated with a significantly higher all-cause mortality at 5 years compared with SAVR. Of note, all-cause mortality presented a characteristic temporal pattern showing increased risk between 2 and 5 years but not within 2 years. Longer-term follow-up data are warranted.

Suppression of p66Shc prevents hyperandrogenism-induced ovarian oxidative stress and fibrosis.

BACKGROUND: Rats with hyperandrogen-induced polycystic ovary syndrome (PCOS) have been shown to develop ovarian oxidative stress (OS) and fibrosis. The Sirt1 agonist, resveratrol, can reduce OS through inhibiting p66Shc in other models of OS. METHODS: We created a rat PCOS model with increased OS levels following treatment with one of the two androgens, dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT). The PCOS related features were determined by measurement of malondialdehyde (MDA) and superoxide dismutase (SOD) levels or by examining the reactive oxygen species (ROS) levels using the DCF-DA probe. The potential mechanisms by which p66Shc/Sirt1 mediates ovarian fibrosis were explored by western blotting, quantitative reverse transcription-PCR, immunofluorescence staining, and immunohistochemistry. RESULTS: Hyperandrogen dramatically augmented OS and activation of fibrotic factors in the ovary. Our data demonstrated that treatment with resveratrol enhanced Sirt1 and decreased ovarian OS as well as inhibited phosphorylation of p66Shc both in vivo and in vitro. The treatment suppressed fibrotic factor activation and improved ovarian morphology. Lentivirus- or siRNA-mediated p66Shc knockdown resulted in a dramatic enhancement of Sirt1 expression, down-regulation of ROS and suppression of fibrotic factors in granulosa cells. Moreover, p66Shc overexpression markedly increased the expression of fibrotic factors. Additionally, silencing Sirt1 induced a dramatic increase in p66Shc and enhanced activation of fibrotic factors. CONCLUSIONS: p66Shc may be a direct target of Sirt1 for inducing ROS and thus promoting fibrosis. Further exploration of the mechanisms of p66Shc in both fibrosis and OS may provide novel therapeutic strategies that will facilitate the improvement in PCOS symptoms and reproductive functions.

Highly Graphitized Porous Carbon-FeNi3 Fabricated from Oleic Acid for Advanced Lithium-Sulfur Batteries.

Improving the electrical conductivity of sulfur, suppressing shuttle/dissolution of polysulfide, and enhancing reaction kinetics in Li-S batteries are essential for practical applications. Here, for the first time, we have used inexpensive oleic acid as a single carbon source, and have added commercial SiO2 as a template to form a porous structure, whereas introducing Fe(NO3 )3 and Ni(NO3 )2 as catalysts to increase the degree of graphitization. Moreover, the dual metal salts Fe(NO3 )3 and Ni(NO3 )2 can also form FeNi3 alloy, and our results show that FeNi3 nanoparticles accelerate the kinetic conversion reactions of polysulfide. By virtue of the well-developed porous structure and high degree of graphitization, the highly graphitized porous carbon-FeNi3 (GPC-FeNi3 ) has high conductivity to ensure fast charge transfer, and the hierarchically porous structure facilitates ion diffusion and traps polysulfide. Thus, a GPC-FeNi3 /S cathode displays excellent electrochemical performance. At current rates of 0.2 and 1 C, a cathode of the GPC-FeNi3 /S composite with a sulfur content of 70 % delivers high initial discharge capacities of 1108 and 880 mA h g-1 , respectively, and retains reversible specific capacities of 850 mA h g-1 after 200 cycles at 0.2 C and 625 mA h g-1 after 400 cycles at 1 C.

Long non-coding RNA MEG3 knockdown attenuates endoplasmic reticulum stress-mediated apoptosis by targeting p53 following myocardial infarction.

Mounting evidence has indicated that long non-coding RNA maternally expressed gene 3 (lncRNA MEG3) regulates cell apoptosis, and is involved in a variety of diseases. However, its exact role in myocardial infarction (MI) has not been fully elucidated. In the present study, we firstly observed that the expression levels of the lncRNA MEG3 in infarct hearts and hypoxic neonatal mice ventricular myocytes (NMVMs) were up-regulated by quantitative real-time PCR (qRT-PCR). Then, we knocked down lncRNA MEG3 by lentiviral delivery in the myocardial border region following multipoint injection. Following 28 days of MI, the lncRNA MEG3 knockdown mice indicated better cardiac function, and less cardiac remodelling by ultrasonic cardiogram and histological analysis. In addition, we indicated that lncRNA MEG3 knockdown reduced myocyte apoptosis and reactive oxygen species production in MI mice model and hypoxic NMVMs. Furthermore, we revealed that knockdown of lncRNA MEG3 protected against endoplasmic reticulum stress (ERS)-mediated myocardial apoptosis including the induction of PERK-eIF2α and caspase 12 pathways. At last, we provided evidence that p53 was identified as a protein target of lncRNA MEG3 to regulate NF-κB- and ERS-associated apoptosis. Taken collectively, our findings demonstrated that lncRNA MEG3 knockdown exerted cardioprotection by reducing ERS-mediated apoptosis through targeting p53 post-MI.

Residual flow may increase the risk of adverse events in patients received combined catheter ablation and transcatheter left atrial appendage closure for nonvalvular atrial fibrillation: a meta-analysis.

BACKGROUND: Catheter ablation (CA) and left atrial appendage closure (LAAC) have been combined into a novel one-stop procedure for patients with atrial fibrillation (AF). However, postoperative complications are relatively common in patients undergoing LAAC; the complications, including residual flow, increase in the risk of bleeding, or other adverse events, are unknown in patients receiving one-stop therapy. Therefore, we tried to evaluate the adverse events of CA and LAAC hybrid therapy in patients with nonvalvular AF. METHODS: We performed a meta-analysis and computer-based literature search to identify publications listed in the PubMed, Embase, and Cochrane library databases. Studies were included if patients received CA and LAAC hybrid therapy and reported adverse events. RESULTS: Overall 13 studies involving 952 patients were eligible based on the inclusion criteria. In the periprocedural period, the pooled incidence of pericardial effusion was 3.15%. The rates of bleeding events and residual flow were 5.02 and 9.11%, respectively. During follow-up, the rates of all-cause mortality, embolism events, bleeding events, AF recurrence, and residual flow were 2.15, 5.24, 6.95, 32.89, and 15.35%, respectively. The maximum occurrence probability of residual flow events was 21.87%. Bleeding events were more common in patients with a higher procedural residual flow event rate (P = 0.03). A higher AF recurrence rate indicated higher rates of embolism events (P = 0.04) and residual flow (P = 0.03) during follow-up. CONCLUSIONS: Bleeding events were more common in patients with a higher procedural residual flow event rate. However, combined CA and LAAC therapy is reasonably safe and efficacious in patients with nonvalvular AF. Further studies on the safety and efficacy of CA or LAAC alone are necessary in future.

Synthesis, Self-Assembly and Characterization of Tandem Triblock BPOSS-PDI-X Shape Amphiphiles.

In this article, we report the facile synthesis, self-assembly, and characterization of shape amphiphiles (BPOSS-PDI-X) based on isobutyl-functionalized polyhedral oligomeric silsesquioxane (BPOSS), perylene tetracarboxylic diimide (PDI), and (60)fullerene (C60) moieties. Firstly, an asymmetrically functionalized diblock shape amphiphile precursor (BPOSS-PDI-OH) was obtained through the one-pot reaction between perylene-3,4,9,10-tetracarboxylic dianhydride and two different amines, namely BPOSS-NH2 and 3-amino-1-propanol. It was further conjugated with C60-COOH to give a tri-block shape amphiphile (BPOSS-PDI-C60). Their chemical structures were thoroughly characterized by NMR, IR and MALDI-TOF MS spectrometry. In order to gain insights on the structure-property relationship, their self-assembly in gas phase, in solution, and in solid state were characterized using traveling wave ion mobility mass spectrometry (TWIM-MS), UV/Vis absorption, fluorescence emission spectrophotometer, and transmission electron microscopy, respectively. It was found that BPOSS-PDI-OH formed more complicated dimers than BPOSS-PDI-C60. Both samples showed unique aggregation behaviors in solution with increasing concentration, which could be attributed neither to H- nor to J-type and might be related to the discrete dimers. While BPOSS-PDI-C60 could hardly crystalize into ordered structures, BPOSS-PDI-OH could form nanobelt-shaped single crystals, which may hold potential applications in microelectronics.

Percutaneous closure versus medical therapy for stroke with patent foramen Ovale: a systematic review and meta-analysis.

BACKGROUND: Patent foramen ovale (PFO) closure has emerged as a secondary prevention option in patients with PFO and cryptogenic stroke. However, the comparative efficacy and safety of percutaneous closure and medical therapy in patients with cryptogenic stroke and PFO remain unclear. METHODS: Randomized controlled trials (RCTs) and comparative observational studies that compared PFO closure against medical therapy, each with a minimal of 20 patients in the closure arm and 1-year follow-up were included. RESULTS: We analyzed 6961 patients from 20 studies (5 RCTs and 15 observational studies) with a median follow-up of 3.1 years. Moderate-quality evidence showed that PFO closure was associated with a significantly lower incidence of the composite outcome of ischemic stroke, transient ischemic attack (TIA), or all-cause death (odds ratio [OR]: 0.57; 95% confidence interval [CI]: 0.38 to 0.85; P = 0.006), mainly driven by lower incidence of stroke (OR: 0.39; 95% CI: 0.24 to 0.63; P < 0.001). The numbers needed to treat were 43 and 39 for the composite outcome and recurrent ischemic stroke respectively. PFO closure increased the risks for atrial fibrillation or atrial flutter (OR: 5.74; 95% CI: 3.08 to 10.70; P < 0.001; high-quality evidence) and pulmonary embolism (OR: 3.03; 95% CI: 1.06 to 8.63; P = 0.038; moderate-quality evidence), with the numbers needed to harm being 30 and 143 respectively. The risks for TIA, all-cause death, and major bleeding were not statistically different. Analyses limited to RCTs showed similar findings, as did a series of other subgroup analyses. CONCLUSION: In conclusion, PFO closure reduced the incidences of stroke and the composite outcome of ischemic stroke, TIA, or all-cause death, but increased risks for atrial fibrillation or atrial flutter and pulmonary embolism compared with medical therapy.

Joint sparse reconstruction of multi-contrast MRI images with graph based redundant wavelet transform.

BACKGROUND: Multi-contrast images in magnetic resonance imaging (MRI) provide abundant contrast information reflecting the characteristics of the internal tissues of human bodies, and thus have been widely utilized in clinical diagnosis. However, long acquisition time limits the application of multi-contrast MRI. One efficient way to accelerate data acquisition is to under-sample the k-space data and then reconstruct images with sparsity constraint. However, images are compromised at high acceleration factor if images are reconstructed individually. We aim to improve the images with a jointly sparse reconstruction and Graph-based redundant wavelet transform (GBRWT). METHODS: First, a sparsifying transform, GBRWT, is trained to reflect the similarity of tissue structures in multi-contrast images. Second, joint multi-contrast image reconstruction is formulated as a ℓ2, 1 norm optimization problem under GBRWT representations. Third, the optimization problem is numerically solved using a derived alternating direction method. RESULTS: Experimental results in synthetic and in vivo MRI data demonstrate that the proposed joint reconstruction method can achieve lower reconstruction errors and better preserve image structures than the compared joint reconstruction methods. Besides, the proposed method outperforms single image reconstruction with joint sparsity constraint of multi-contrast images. CONCLUSIONS: The proposed method explores the joint sparsity of multi-contrast MRI images under graph-based redundant wavelet transform and realizes joint sparse reconstruction of multi-contrast images. Experiment demonstrate that the proposed method outperforms the compared joint reconstruction methods as well as individual reconstructions. With this high quality image reconstruction method, it is possible to achieve the high acceleration factors by exploring the complementary information provided by multi-contrast MRI.

IDO and TDO as a potential therapeutic target in different types of depression.

Depression is highly prevalent worldwide and a leading cause of disabilty. However, the medications currently available to treat depression fail to adequately relieve depressive symptoms for a large number of patients. Research into the aberrant overactivation of the kynurenine pathway and the production of various active metabolites has brought new insight into the progression of depression. IDO and TDO are the first and rate-limiting enzymes in the kynurenine pathway and regulate the production of active metabolites. There is substantial evidence that TDO and IDO enzyme are activated during depression, and therefore, IDO and TDO inhibitors have been identified as ideal therapeutic targets for depressive disorder. Hence, this review will focus on the kynurenine branch of tryptophan metabolism and describe the role of IDO and TDO in the pathology of depression. In addition, this review will compare the relative imbalance between KYNA and neurotoxic kynurenine metabolites in different psychiatric disorders. Finally, this review is also directed toward assessing whether IDO and TDO are potential therapeutic target in depression associated with other diseases such as diabetes and/or cancer, as well as the development of potent IDO and TDO inhibitors.

Mid- and Long-Term Outcome Comparisons of Everolimus-Eluting Bioresorbable Scaffolds Versus Everolimus-Eluting Metallic Stents: A Systematic Review and Meta-analysis.

BACKGROUND: Percutaneous coronary interventions to implant bioresorbable vascular scaffolds (BVSs) were designed to reduce the late thrombotic events that occur with metallic stents. PURPOSE: To estimate the incidence of scaffold thrombosis after BVS implantation and compare everolimus-eluting BVSs with everolimus-eluting metallic stents (EESs) in terms of safety and efficacy at mid- and long-term follow-up in adults who had a percutaneous coronary intervention. DATA SOURCES: PubMed, EMBASE, the Cochrane Library, conference proceedings, and relevant Web sites from inception until 20 May 2017, without language restriction. STUDY SELECTION: 7 randomized trials and 38 observational studies (each with a minimum of 6 months and 100 patient-years of follow-up) in adults with coronary artery disease who had a BVS or an EES and reported scaffold or stent thrombosis (main outcome) or other secondary outcomes (such as death, myocardial infarction, or revascularization). DATA EXTRACTION: 2 reviewers independently extracted study data, rated study quality, and assessed strength of evidence. DATA SYNTHESIS: The pooled incidence of definite or probable scaffold thrombosis after BVS implantation was 1.8% (95% CI, 1.5% to 2.2%) at a median follow-up of 1 year (41 studies, 21 884 patients) and 0.8% (CI, 0.5% to 1.3%) beyond 1 year (14 studies, 4688 patients). Seven trials involving 5578 patients that directly compared BVSs with EESs showed an increased risk for definite or probable scaffold thrombosis (odds ratio [OR], 3.40 [CI, 2.01 to 5.76]) with BVSs at a median follow-up of 25 months. Increased risks were present at early (prominently subacute), late, and very late stages, and odds beyond 1 year were almost double those seen within 1 year. Bioresorbably vascular scaffolds increased risks for myocardial infarction (OR, 1.63 [CI, 1.26 to 2.10]), target lesion revascularization (OR, 1.31 [CI, 1.03 to 1.67]), and target lesion failure (OR, 1.37 [CI, 1.12 to 1.66]); the odds for these 3 end points also increased over time. The incidences of all-cause, cardiac, and noncardiac death and of target vessel and any revascularization did not differ. LIMITATION: Quality of observational studies was unclear, and some data were unpublished. CONCLUSION: Compared with EESs, BVSs increased the risks for scaffold thrombosis and other thrombotic events at mid- and long-term follow-up, and risks increased over time. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China.

Effects of aprepitant on the pharmacokinetics of imatinib and its main metabolite in rats.

Aprepitant (APT), an antiemetic drug belonging to the class of substance P antagonists is efficiently used in both acute and delayed chemotherapy-induced nausea and vomiting. Nausea and vomiting induced by imatinib (IMA) as a chemotherapeutic drug could be reduced by APT. This study investigated the effect of APT on the pharmacokinetics of IMA and its major metabolite N-desmethyl imatinib (N-D IMA) in rats and the mechanism of this drug-drug interaction. The results indicated that after 3 days of pretreatment with APT (10 mg/kg), the blood concentration of IMA was decreased in both of oral and intravenous routes of IMA administration compared to vehicle treated rats, whereas the blood concentration of N-D IMA was not significantly changed. The total clearance (CL/F) of oral and intravenous given IMA was increased by 1.41 and 1.32-fold, and the bioavailability was greatly decreased about 30.43% and 24.40% respectively. At this time, the P-gp and the hepatic CYP3A1 were increased at both the mRNA and protein levels. These results demonstrated that ingestion of APT will decrease the bioavailability of IMA to a significant extent in rats and the drug-drug interaction between APT and IMA appears to be due to modulation of P-gp and CYP3A1.

Percutaneous intervention versus coronary artery bypass graft surgery in left main coronary artery stenosis: a systematic review and meta-analysis.

BACKGROUND: The optimal revascularization technique in patients with left main coronary artery disease (CAD) remains controversial. We aimed to compare the long-term performance of percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) surgery in treatment of left main CAD. METHODS: PubMed, EMBASE, and the Cochrane Library were searched until November 16, 2016. RESULTS: Six randomized controlled trials and 22 matched observational studies including 22,487 patients and 90,167 patient-years of follow-up were included. PCI was associated with an overall higher risk for the major adverse cardiac and cerebrovascular events (hazard ratio (HR), 1.42; 95% confidence interval (CI), 1.14-1.77), mainly driven by higher rates of myocardial infarction (HR, 1.69; 95% CI, 1.22-2.34) and revascularization (HR, 2.80; 95% CI, 1.86-4.22). The overall risks for all-cause death (HR, 1.05; 95% CI, 0.93-1.20), cardiac death (HR, 1.05; 95% CI, 0.69-1.59), stroke (HR, 0.64; 95% CI, 0.33-1.24), and the composite safety endpoint of death, myocardial infarction, or stroke (HR, 1.06; 95% CI, 0.97-1.16) were similar between PCI and CABG. Stratified analysis based on stent types showed that the increased risk for myocardial infarction associated with PCI was only evident in patients with bare-metal stents or early-generation drug-eluting stents (DES), but not newer-generation DES. Stratified analyses based on study designs showed largely similar findings with the overall analyses, except for a significantly higher incidence of myocardial infarction in adjusted studies (HR, 2.01; 95% CI, 1.64-2.45) but a trend toward higher incidence in randomized trials (HR, 1.39; 95% CI, 0.85-2.27) associated with PCI. CONCLUSIONS: Compared with CABG, PCI with newer-generation DES might be a safe alternative revascularization strategy for treatment of left main CAD, but is associated with more repeat revascularization.

Discovery of hierarchical superstructures in block copolymers by integrating different liquid crystalline interactions.

Hierarchically assembled superstructures of block copolymers are discovered by introduction of the competition of anisotropy attributed from liquid crystalline ordering and nano-phase separation. When the two prototypical fields of liquid crystals (LCs), smectics (S) and nematics (N), are adjoined within the framework of diblock copolymers (S-N) in a variety of precisely tuned compositions, a novel class of superlattices with an interdigitated array of smectic layers between the nearest lamellae or cylinders are observed. This generates unconventional nano-phase separated orthorhombic (Lo) and pseudo-hexagonal (Ho) structures, where the stretched N tethers, projected regularly from the S layers, could transfer the local organization and guide the correlated assembly. This type of superstructure is highly frustrated in reversed cylindrical morphology and absent in S-coil diblock copolymers. The collective interplay of the S and N interactions with nano-phase separation induces the formation of the final complex yet equilibrium structures, providing unprecedented opportunities towards exquisite structural diversity.

Comparative Efficacy and Safety of Everolimus-Eluting Bioresorbable Scaffold Versus Everolimus-Eluting Metallic Stents: A Systematic Review and Meta-analysis.

BACKGROUND: Theoretically, the everolimus-eluting bioresorbable vascular scaffold (BVS) could eliminate stent thrombosis and improve outcomes in patients having percutaneous coronary intervention. PURPOSE: To estimate the incidence of stent thrombosis after BVS implantation and to compare the efficacy and safety of BVSs versus everolimus-eluting metallic stents (EESs) in adults having percutaneous coronary intervention. DATA SOURCES: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, conference proceedings, and relevant Web sites from inception through 20 January 2016. STUDY SELECTION: 6 randomized, controlled trials and 38 observational studies, each involving at least 40 patients with BVS implantation. DATA EXTRACTION: Two reviewers independently extracted study data and evaluated study risk of bias. DATA SYNTHESIS: The pooled incidence of definite or probable stent thrombosis after BVS implantation was 1.5 events per 100 patient-years (PYs) (95% CI, 1.2 to 2.0 events per 100 PYs) (126 events during 8508 PYs). Six randomized trials that directly compared BVSs with EESs showed a non-statistically significant increased risk for stent thrombosis (odds ratio [OR], 2.05 [CI, 0.95 to 4.43]; P = 0.067) and myocardial infarction (OR, 1.38 [CI, 0.98 to 1.95]; P = 0.064) with BVSs. The 6 observational studies that compared BVSs with EESs showed increased risk for stent thrombosis (OR, 2.32 [CI, 1.06 to 5.07]; P = 0.035) and myocardial infarction (OR, 2.09 [CI, 1.23 to 3.55]; P = 0.007) with BVSs. The relative rates of all-cause and cardiac death, revascularization, and target lesion failure were similar for BVSs and EESs. LIMITATION: Scarce comparative data, no published data from large trials with long-term follow-up, and limited quality and incomplete reporting of observational studies. CONCLUSION: Compared with EESs, BVSs do not eliminate and might increase risks for stent thrombosis and myocardial infarction in adults having percutaneous coronary intervention. Results of large trials with long-term follow-up are critically needed to establish the safety or at least the noninferiority of BVSs compared with EESs. PRIMARY FUNDING SOURCE: None.