A case of atrial tachycardia originating from the left atrial roof successfully ablated via the pulmonary artery approach.

A 60-year-old male patient suffered from frequent episodes of atrial tachycardia (AT), after the index procedure of catheter ablation for paroxysmal atrial fibrillation. During the repeat procedure, the activation map showed that the earliest activation site was located at the roof of left atrium. Multiple ablations at the earliest activation site on the roof failed to terminate the AT; however, ablation within the pulmonary artery at an adjacent anatomical site successfully eliminated the AT, even without recording distinct near-field potential.

Regulation of the biosynthesis of endogenous nitric oxide and abscisic acid in stored peaches by exogenous nitric oxide and abscisic acid.

BACKGROUND: Nitric oxide (NO) and abscisic acid (ABA) are important regulators of plant response to cold stress, and they interact in response to cold signals. The primary goal of this study was to determine the roles of exogenous NO and ABA on the synthesis of endogenous NO and ABA in cold-stored peach fruit. RESULTS: Exogenous NO and ABA maintained a relatively high content of NO, increased nitrate reductase (NR) activity, and inhibited the activity of NO synthase (NOS)-like and the levels of polyamine biosynthesis in peaches during cold storage. Treatments of potassium 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), NO, N-nitro-l-Arg-methyl ester (L -NAME), and sodium tungstate did not influence ABA content. Exogenous ABA increased the content of carotenoids and the activities of aldehyde oxidase (AO), 9-cis-epoxycarotenoid dioxygenase (NCED), and zeaxanthin epoxidase (ZEP) of ABA synthesis in peaches during cold storage, and upregulated the gene expression of PpAO1, PpNCED1, PpNCED2, and PpZEP. The production of endogenous NO was differentially inhibited by NO scavengers, ABA inhibitors, and NR inhibitors, but not affected by NOS-like inhibitors during cold storage. CONCLUSION: Exogenous NO and ABA can induce endogenous NO synthesis in cold-stored peaches by the nitrate reductase pathway, and ABA can mediate endogenous ABA synthesis by the autocatalytic reaction. NO does not regulate ABA synthesis. © 2019 Society of Chemical Industry.

Interactive effects of abscisic acid and nitric oxide on chilling resistance and active oxygen metabolism in peach fruit during cold storage.

BACKGROUND: Cold conditions can accelerate the production of reactive oxygen species (ROS), and excessive ROS may attack biological macromolecules, disrupt related signal pathways, induce oxidative stress and influence plant metabolism. The cross-talk between nitric oxide (NO) and abscisic acid (ABA) and the inhibitions by NO or ABA on oxidative damage have been reported in fruits. However, there are few reports about the roles of NO-ABA interactions in chilling stress and antioxidant defense in fruits during cold storage. This study was conducted to investigate the roles of NO, ABA and interactions between NO and ABA in response to chilling stress on peach fruit (Prunus persica (L.) Batsch, cv. 'Xintaihong'). RESULTS: Treatments with 15 µmol L-1 NO, 100 µmol L-1 ABA and 15 µmol L-1 NO + 5 mmol L-1 sodium tungstate solution could reduce ROS content, alleviate lipid peroxidation and enhance antioxidant enzyme activities and antioxidant capacities. However, treatments with 5 µmol L-1 potassium 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), 5 mmol L-1 sodium tungstate and 100 µmol L-1 ABA + 5 µmol L-1 c-PTIO differentially blocked these protective effects and significantly increased ROS content and lipid peroxidation of peaches under low-temperature conditions. CONCLUSIONS: Application of exogenous ABA could increase the resistance to cold-induced oxidative stress by enhancing the efficiency of enzymatic and non-enzymatic systems, which were partially mediated by NO. © 2018 Society of Chemical Industry.

Expression of ILK in renal stroma is essential for multiple aspects of renal development.

Kidney development involves reciprocal and inductive interactions between the ureteric bud (UB) and surrounding metanephric mesenchyme. Signals from renal stromal lineages are essential for differentiation and patterning of renal epithelial and mesenchymal cell types and renal vasculogenesis; however, underlying mechanisms remain not fully understood. Integrin-linked kinase (ILK), a key component of integrin signaling pathway, plays an important role in kidney development. However, the role of ILK in renal stroma remains unknown. Here, we ablated ILK in renal stromal lineages using a platelet-derived growth factor receptor B ( Pdgfrb) -Cre mouse line, and the resulting Ilk mutant mice presented postnatal growth retardation and died within 3 wk of age with severe renal developmental defects. Pdgfrb-Cre;Ilk mutant kidneys exhibited a significant decrease in UB branching and disrupted collecting duct formation. From E16.5 onward, renal interstitium was disorganized, forming medullary interstitial pseudocysts. Pdgfrb-Cre;Ilk mutants exhibited renal vasculature mispatterning and impaired glomerular vascular differentiation. Impaired glial cell-derived neurotrophic factor/Ret and bone morphogenetic protein 7 signaling pathways were observed in Pdgfrb-Cre;Ilk mutant kidneys. Furthermore, phosphoproteomic and Western blot analyses revealed a significant dysregulation of a number of key signaling pathways required for kidney morphogenesis, including PI3K/AKT and MAPK/ERK in Pdgfrb-Cre;Ilk mutants. Our results revealed a critical requirement for ILK in renal-stromal and vascular development, as well as a noncell autonomous role of ILK in UB branching morphogenesis.

Discrete potentials guided radiofrequency ablation for idiopathic outflow tract ventricular arrhythmias.

AIMS: Discrete potentials (DPs) have been recorded and targeted as the site of ablation of the outflow tract arrhythmias. The aim of the present study was to investigate the significance of DPs with respect to mapping and ablation for idiopathic outflow tract premature ventricular contractions (PVCs) or ventricular tachycardias (VTs). METHODS AND RESULTS: Seventeen consecutive patients with idiopathic right or left ventricular outflow tract PVCs/VTs who underwent radiofrequency catheter ablation were included. Intracardiac electrograms during the mapping and ablation were analysed. During sinus rhythm, sharp high-frequency DPs that displayed double or multiple components were recorded following or buried in the local ventricular electrograms in all of the 17 patients, peak amplitude 0.51 ± 0.21 mV. The same potential was recorded prior to the local ventricular potential of the PVCs/VTs. Spontaneous reversal of the relationship of the DPs to the local ventricular electrogram during the arrhythmias was noted. The DPs were related to a region of low voltage showed by intracardiac high-density contact mapping. At the sites with DPs, lower unipolar and bipolar ventricular voltage of sinus beats were noted compared with the adjacent regions without DPs (unipolar: 6.1 ± 1.8 vs. 8.3 ± 2.3 mV, P < 0.05; bipolar: 0.62 ± 0.45 vs. 1.03 ± 0.60 mV, P < 0.05). The targeted DPs were still present in 12 patients after successful elimination of the ectopies. Discrete potentials were not present in seven controls. CONCLUSION: Discrete potentials and related low-voltage regions were common in idiopathic outflow tract ventricular arrhythmias. Discrete potential- and substrate-guided ablation strategy will help to reduce the recurrence of idiopathic outflow tract arrhythmias.

Research hotspots and trends of complementary and alternative therapy for neuropathic pain: A bibliometric analysis.

BACKGROUND: Neuropathic pain (NP) is a common type of pain in clinic. Due to the limited effect of drug treatment, many patients with NP are still troubled by this disease. In recent years, complementary and alternative therapy (CAT) has shown good efficacy in the treatment of NP. As the interest in CAT for NP continues to grow, we conducted a bibliometric study of publications on CAT treatment for NP. The aim of this study is to analyze the development overview, research hotspots and future trends in the field of CAT and NP through bibliometric methodology, so as to provide a reference for subsequent researchers. METHODS: Publications on CAT in the treatment of NP from 2002 to 2022 were retrieved from the Web of Science Core Collection. Relevant countries, institutions, authors, journals, keywords, and references were analyzed bibliometrically using Microsoft Excel 2021, bibliometric platform, VOSviewer, and CiteSpace. RESULTS: A total of 898 articles from 46 countries were published in 324 journals, and they were contributed by 4455 authors from 1102 institutions. The most influential country and institution are China (n = 445) and Kyung Hee University (n = 63), respectively. Fang JQ (n = 27) and Evidence-Based Complementary and Alternative Medicine (n = 63) are the author and journal with the most publications in this field. The clinical efficacy, molecular biological mechanisms and safety of CAT for NP are currently hot directions. Low back pain, postherpetic neuralgia, acupuncture, and herbal are the hot topics in CAT and NP in recent years. CONCLUSION: This study reveals the current status and hotspots of CAT for NP. The study also indicates that the effectiveness and effect mechanism of acupuncture or herbs for treating emotional problems caused by low back pain or postherpetic neuralgia may be a trend for future research.

Examining the U-shaped relationship of sleep duration and systolic blood pressure with risk of cardiovascular events using a novel recursive gradient scanning model.

Background: Observational studies have suggested U-shaped relationships between sleep duration and systolic blood pressure (SBP) with risks of many cardiovascular diseases (CVDs), but the cut-points that separate high-risk and low-risk groups have not been confirmed. We aimed to examine the U-shaped relationships between sleep duration, SBP, and risks of CVDs and confirm the optimal cut-points for sleep duration and SBP. Methods: A retrospective analysis was conducted on NHANES 2007-2016 data, which included a nationally representative sample of participants. The maximum equal-odds ratio (OR) method was implemented to obtain optimal cut-points for each continuous independent variable. Then, a novel "recursive gradient scanning method" was introduced for discretizing multiple non-monotonic U-shaped independent variables. Finally, a multivariable logistic regression model was constructed to predict critical risk factors associated with CVDs after adjusting for potential confounders. Results: A total of 26,691 participants (48.66% were male) were eligible for the current study with an average age of 49.43 ± 17.69 years. After adjusting for covariates, compared with an intermediate range of sleep duration (6.5-8.0 h per day) and SBP (95-120 mmHg), upper or lower values were associated with a higher risk of CVDs [adjusted OR (95% confidence interval) was 1.20 (1.04-1.40) for sleep duration and 1.17 (1.01-1.36) for SBP]. Conclusions: This study indicates U-shaped relationships between SBP, sleep duration, and risks of CVDs. Both short and long duration of sleep/higher and lower BP are predictors of cardiovascular outcomes. Estimated total sleep duration of 6.5-8.0 h per day/SBP of 95-120 mmHg is associated with lower risk of CVDs.

Complete Atrioventricular Block Caused by Retrograde Transaortic Approach.

A 61-year-old female was referred for catheter ablation of symptomatic and frequent premature ventricular complexes presented with right bundle branch block and a prominent inferior frontal plane QRS axis. A retrograde transaortic approach was routinely performed. A sustained complete atrioventricular block was repeatedly encountered while the ablation catheter was attempting to cross the aortic valve with different curves and manipulations. The procedure was abandoned. The mechanical atrioventricular block could only have been caused by the retrograde transaortic approach. We should be cautious when performing a retrograde transaortic catheter manipulation in some patients.

Efficient Interfacial Charge Transfer Based on 2D/2D Heterojunctions of Fe-C3N4/Ti3C2 for Improving the Photocatalytic Degradation of Antibiotics.

Graphitic carbon nitride (g-C3N4) has shown to be a promising photocatalyst that, however, suffers from strong charge recombination and poor conductivity, while MXenes have shown to be perfect cocatalysts for the photocatalytic process but show poor stability. In this study, we successfully constructed 2D/2D heterojunctions of Fe-C3N4/Ti3C2 for the photocatalytic degradation of antibiotics. In this study, multilayer Ti3C2 was obtained by etching Ti3AlC2, and then Fe-C3N4/Ti3C2 photocatalyst was prepared by the one-pot microwave method and high-temperature calcination method. The synthesized samples were characterized by XRD, SEM, TEM, XPS, TGA, BET, DRS, PL, and other means. The photocatalytic degradation of tetracycline hydrochloride by Fe-C3N4/Ti3C2 was in accordance with the first-order reaction kinetics model, and the apparent rate constant k was 2.83, 2.06, and 1.77 times that of g-C3N4, Fe-C3N4, and g-C3N4/Ti3C2, respectively. Through the mechanism study, it was shown that the most active species in the reaction system was • O2 -, while h+ and •OH had a relatively lower effect on the degradation system.

Clinical efficacy of "ICE-FIRE" ablation for non-paroxysmal atrial fibrillation.

PURPOSE: Catheter ablation is less successful for non-paroxysmal atrial fibrillation (NPAF) according to numerous follow-up studies. The choice of ablation strategy for patients with NPAF remains controversial. The objective of the study was to explore the clinical efficacy of the "ICE-FIRE" ablation. METHODS: Ninety NPAF patients were enrolled. Patients were randomly divided into RF (treated with circumferential pulmonary vein isolation (CPVI) and additional substrate modification by radiofrequency ablation) group and I-F (treated with CPVI by cryoablation and additional substrate modification by radiofrequency ablation) group. After CPVI and cardioversion to sinus rhythm, high-density mapping was performed. Eight-one of 90 participants restored to sinus rhythm. Seventy-four of 81 NPAF patients showed low-voltage zone. Substrates with low-voltage zone were targeted for further modification. Participants were followed at baseline, 3, 6, 9, and 12 months after the initial ablation. RESULTS: The I-F group shared more X-ray exposure (I-F, 264.4 ± 97.4 mGy; RF, 224.9 ± 62.0 mGy; P = 0.039) and less duration of the procedure (I-F, 150.3 ± 27.5 min; RF, 174.2 ± 38.5 min; P = 0.003) compared to RF group. The freedom from atrial arrhythmia recurrence at 12 months post-ablation was similar between the RF and I-F groups (RF, 57.1%; I-F, 71.8%; P = 0.197). However, I-F group experienced lower rehospitalization rate of AF recurrence (RF, 42.9%; I-F, 20.5%; P = 0.038). CONCLUSIONS: In NPAF patients requiring substrate mapping and modification, the "ICE-FIRE" ablation demonstrated non-inferior clinical efficacy and lower rehospitalization rate of AF recurrence when compared with pure radiofrequency ablation strategy.

Evaluation of local aggressive lung therapy versus systemic therapy in oligometastatic non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Previous studies have shown the feasibility and effectiveness of local aggressive thoracic therapy (surgery and radiotherapy) for oligometastatic non-small cell lung cancer compared with systemic therapy, but with small sample. This study aims to perform a pooled analysis to explore whether LT could improve outcomes of oligometastatic patients with non-small cell lung cancer. METHODS: Protocol of present study was registered on PROSPERO as number: CRD42021233095. PubMed, Embase and Web of knowledge were searched, and eligible studies investigating local therapy for non-small cell lung cancer with 1-5 metastases regardless of organs were included. Linear regression between survival and clinical characteristics were conducted. Hazard ratios of survival and adverse effects were merged. Pooled survival curves were carried out. RESULTS: Three randomized controlled trials and 5 cohort studies enrolling 499 patients were included. There was a trend that median overall survival declined with the increasing proportion of N2-3 positive patients in local therapy group, but with no statistical difference (P=0.09, R2=0.98). Undergoing local therapy for oligometastatic non-small cell lung cancer achieved reduction of 47% and 60% in the risk of death and cancer progression (P<0.001), respectively. In subgroup analysis, patients receiving local therapy including surgery showed hazard ratio of 0.33 on progression-free survival and 0.55 of these excluding surgery. Patients receiving consolidative local therapy (local therapy after systemic therapy) obtained hazard ratios 0.33 and 0.45 on progression-free and overall survival vs. systemic therapy, respectively. Hazard ratios of those receiving upfront local therapy (local therapy first) were 0.62 and 0.68 on progression-free and overall survival vs. systemic therapy. Pooled survival analysis showed median overall and progression-free survival of local therapy (21.6 and 14 months) group were both longer than systemic one (14.3 and 6.5 months). Odds ratio of adverse effects were no difference between 2 groups (P=0.16). CONCLUSIONS: Local aggressive thoracic therapy could prolong 7 months overall and progression-free survival compared with systemic therapy in patients with oligometastatic non-small cell lung cancer. Consolidative local therapy might be a more favorable choice of local therapy. Benefits of local therapy for N2-3 positive patients should explored further.

Collaborative ISL1/GATA3 interaction in controlling neuroblastoma oncogenic pathways overlapping with but distinct from MYCN.

Background: Transcription factor ISL1 plays a critical role in sympathetic neurogenesis. Expression of ISL1 has been associated with neuroblastoma, a pediatric tumor derived from sympatho-adrenal progenitors, however the role of ISL1 in neuroblastoma remains unexplored. Method: Here, we knocked down ISL1 (KD) in SH-SY5Y neuroblastoma cells and performed RNA-seq and ISL1 ChIP-seq analyses. Results: Analyses of these data revealed that ISL1 acts upstream of multiple oncogenic genes and pathways essential for neuroblastoma proliferation and differentiation, including LMO1 and LIN28B. ISL1 promotes expression of a number of cell cycle associated genes, but represses differentiation associated genes including RA receptors and the downstream target genes EPAS1 and CDKN1A. Consequently, Knockdown of ISL1 inhibits neuroblastoma cell proliferation and migration in vitro and impedes tumor growth in vivo, and enhances neuronal differentiation by RA treatment. Furthermore, genome-wide mapping revealed a substantial co-occupancy of binding regions by ISL1 and GATA3, and ISL1 physically interacts with GATA3, and together they synergistically regulate the aforementioned oncogenic pathways. In addition, analyses of the roles of ISL1 and MYCN in MYCN-amplified and MYCN non-amplified neuroblastoma cells revealed an epistatic relationship between ISL1 and MYCN. ISL1 and MYCN function in parallel to regulate common yet distinct oncogenic pathways in neuroblastoma. Conclusion: Our study has demonstrated that ISL1 plays an essential role in neuroblastoma regulatory networks and may serve as a potential therapeutic target in neuroblastoma.

Reactive oxygen species mediated oxidative stress links diabetes and atrial fibrillation.

Diabetes is an independent risk factor for atrial fibrillation (AF); however, the underlying mechanism linking diabetes and AF remains to be clarified. The present study aimed to explore the molecular mechanism of increased reactive oxygen species (ROS) production in AF and the ROS­mediated downstream events in diabetes. Firstly, the atrial fibroblasts were isolated from the left atrium of rabbits using enzyme digestion and differential adhesion. Then, the isolated cells were identified by morphology analysis under a microscope, collagen distribution using Masson trichrome staining and vimentin by immunofluorescence. Following this, the collected atrial fibroblasts were randomly divided into 7 groups and administered with high glucose (25 mM glucose), H2O2 stimulation (100 nmol/l), glucose + apocynin (100 µg/ml), H2O2 + apocynin, glucose + H2O2, and a combination of glucose, apocynin and H2O2, as well as the negative control (NC). An MTS assay was performed to investigate cell proliferation following the different treatments, and western blotting was conducted to explore the expression of several proteins including NAD(P)H oxidative (NOX) subunits, key factors involved in mitogen­activated protein kinase (MAPK) signaling pathways and matrix metalloproteinases (MMPs). The atrial fibroblasts were spindle­shaped with one or more protuberances. Vimentin was positively expressed in collected cells under confocal laser scanning microscopy. This result indicated that the atrial fibroblasts were successfully prepared. High glucose and H2O2 stimulation significantly increased the proliferation of atrial fibroblasts and apocynin markedly attenuated the promoting effects on cell proliferation induced by high glucose and H2O2 treatment (P<0.05). Additionally, high glucose and H2O2 stimulation increased the expression of Rac1, phospho(p)­c­Jun N­terminal kinase 1, p38, p­p38 and MMP9, which was markedly decreased by the addition of apocynin (P<0.05). The mechanism associated with diabetes and AF may be attributed to oxidative stress (ROS production) derived from NOX activity, and then induced activation of the MAPK signaling pathways and MMP9 expression.

Temporal requirements for ISL1 in sympathetic neuron proliferation, differentiation, and diversification.

Malformations of the sympathetic nervous system have been associated with cardiovascular instability, gastrointestinal dysfunction, and neuroblastoma. A better understanding of the factors regulating sympathetic nervous system development is critical to the development of potential therapies. Here, we have uncovered a temporal requirement for the LIM homeodomain transcription factor ISL1 during sympathetic nervous system development by the analysis of two mutant mouse lines: an Isl1 hypomorphic line and mice with Isl1 ablated in neural crest lineages. During early development, ISL1 is required for sympathetic neuronal fate determination, differentiation, and repression of glial differentiation, although it is dispensable for initial noradrenergic differentiation. ISL1 also plays an essential role in sympathetic neuron proliferation by controlling cell cycle gene expression. During later development, ISL1 is required for axon growth and sympathetic neuron diversification by maintaining noradrenergic differentiation, but repressing cholinergic differentiation. RNA-seq analyses of sympathetic ganglia from Isl1 mutant and control embryos, together with ISL1 ChIP-seq analysis on sympathetic ganglia, demonstrated that ISL1 regulates directly or indirectly several distinct signaling pathways that orchestrate sympathetic neurogenesis. A number of genes implicated in neuroblastoma pathogenesis are direct downstream targets of ISL1. Our study revealed a temporal requirement for ISL1 in multiple aspects of sympathetic neuron development, and suggested Isl1 as a candidate gene for neuroblastoma.

Diabetes mellitus and atrial remodeling: mechanisms and potential upstream therapies.

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, and its prevalence has increasing substantially over the last decades. Recent data suggest that there is an increased risk of AF among the patients with diabetes mellitus (DM). However, the potential molecular mechanisms regarding DM-related AF and diabetic atrial remodeling are not fully understood. In this comprehensive review, we would like to summarize the potential relationship between diabetes and atrial remodeling, including structural, electrical, and autonomic remodeling. Also, some upstream therapies, such as thiazolidinediones, probucol, ACEI/ARBs, may play an important role in the prevention and treatment of AF. Therefore, large prospective randomized, controlled trials and further experimental studies should be challengingly continued.