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Purpose The mechanism underlying malignant transformation of vocal fold leukoplakia (VFL) and the precise role of the expression of pepsin in VFL remain unclear. This study aimed to investigate the effects of acidified pepsin on VFL epithelial cell growth and migration, and also identify pertinent molecular mechanisms. Methods Immunochemistry and Western blotting were performed to measure glucose transporter type 1 (GLUT1), monocarboxylate transporters 4 (MCT4), and Hexokinase-II (HK-II) expressions. Cell viability, cell cycle, apoptosis, and migration were investigated by CCK-8 assay, flow cytometry and Transwell chamber assay, respectively. Glycolysis-related contents were determined using the corresponding kits. Mitochondrial HK-II was photographed under a confocal microscope using Mito-Tracker Red. Results It was found: the expression of pepsin and proportion of pepsin+ cells in VFL increased with the increased dysplasia grade; acidified pepsin enhanced cell growth and migration capabilities of VFL epithelial cells, reduced mitochondrial respiratory chain complex I activity and oxidative phosphorylation, and enhanced aerobic glycolysis and GLUT1 expression in VFL epithelial cells; along with the transfection of GLUT1 overexpression plasmid, 18FFDG uptake, lactate secretion and growth and migration capabilities of VFL epithelial cell were increased; this effect was partially blocked by the glycolysis inhibitor 2-deoxy-glucose; acidified pepsin increased the expression of HK-II and enhanced its distribution in mitochondria of VFL epithelial cells. Conclusion It was concluded that acidified pepsin enhances VFL epithelial cell growth and migration abilities by reducing mitochondrial respiratory complex I activity and promoting metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis.

Cryoballoon ablation (CBA) is one of the most commonly used technologies designed for pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF), although the dosing of CBA remains controversial. We evaluated the long-term efficacy and safety of a novel individualized strategy of CBA compared to radiofrequency ablation (RFA) for patients with PAF.In this observational study, symptomatic patients with drug-refractory paroxysmal AF were prospectively consented and enrolled in four centers, being assigned either to the CBA or RFA arm for ablation. In the CBA group, we used a time to isolation (TTI) - based dosing protocol. The primary endpoint was the recurrence of atrial arrhythmia30 s following a 90-day blanking period. The secondary endpoint was procedure-related complications and procedure parameters.A total of 500 patients were recruited in either the CBA group (n = 247) or the RFA group (n = 253) between January 2017 and July 2018. After a median follow-up of 778 days, the atrial tachyarrhythmia-free survival was 71.7% in the CBA group and 67.0% in the RFA group. CBA and RFA displayed similar major or minor complication occurrence, while the former had a significantly shorter procedure duration (82.5 min vs. 141.1 min, p .001) and left atrial dwell time (60.1 min vs. 109.9 min, p .001) but longer fluoroscopy exposure (13.8 min vs. 8.1 min, p .001).Compared to RFA, our TTI-based CBA dosing protocol showed comparable efficacy and safety, with a significantly reduced procedure duration in patients with PAF.

Ceruloplasmin (CP), recognized as a member of multicopper oxidase family, is related to the progression of diverse cancers in human beings. This study is designed to clarify the expression characteristics, biological function and related mechanism of CP in nasopharyngeal carcinoma (NPC).CP expression in NPC tissues and cells was probed by quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) and Western blot. After gain-of-function and loss-of-function models were established, cell counting kit-8 (CCK-8), Transwell and BrdU assays were employed to measure cell viability, migration and invasion. The targeting relationship between microRNA-543 (miR-543) and CP was verified by dual-luciferase reporter gene assay.As against normal nasopharyngeal epithelial tissues, CP expression was significantly lower in NPC tissues, which was associated with higher clinical stage and the short overall survival time. Compared with the control group, CP overexpression markedly restrained the growth, migration and invasion of NPC cells; knocking down CP had the opposite effect. MiR-543 directly targeted CP and negatively modulated its expression.CP restrains the growth, migration and invasion of NPC cells and is negatively regulated by miR-543.

It is a new trend in healthcare informatization construction to build the smart healthcare system by using the Internet of Things (IoT) and cloud. This IoT-oriented and cloud-assisted healthcare system enables the doctor to monitor the patient’s health state to respond to the paroxysmal diseases in real time. Considering the sensitivity of the patient’s privacy, it is necessary to encrypt the cloud-stored health data to prevent the semi-trusted cloud and unauthorized users from accessing them. However, the encrypted health data stored in the cloud brings inconvenience to the retrieval for the data user. In addition, the expensive computational consumption also raises the challenge to the resource-constrained devices in the patient and doctor sides. To support efficient ciphertext retrieval and cope with the performance challenge, in this paper we propose a lightweight attribute-based searchable encryption (LABSE) scheme, which realizes fine-grained access control and keyword search, while reducing the computational overhead for the resource-constrained devices. We rigorously prove the semantic security of the proposed LABSE scheme, and analyze other security properties to response the security requirements under the healthcare scenario. Subsequently, we construct a concrete deployment model for LABSE under the healthcare system. We also compare LABSE with the state-of-art related schemes in terms of functionality and complexity. Finally, we demonstrate the practicality and performance advantages by the experiment.

Achieving simultaneous determination of antibiotic multiresidues in environmental waters by solid phase extraction (SPE) coupled with ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) with detection limits ≤ ng L-1 is still a huge challenge. Moreover, the offline SPE procedure was performed manually, costly, and time-consuming, while the online SPE required precision pretreatment instruments that require highly-skilled personnel. In this paper, a fully automated SPE coupled with UHPLC-MS/MS method was developed for analysis of antibiotics (sulfonamides, quinolones, and macrolides) in water matrices. Sample preparation optimization included SPE materials and configuration (HLB disks), sample volume (500-1000 mL), and pH (pH = 3) with a flow rate at 2~5 mL min-1, and an elution procedure with 2 × 6 mL methanol, and 2 × 6 mL acetone. Meanwhile, the parameters for UHPLC-MS/S detection of analytes were optimized, including LC retention time, and MS parameters. The instrumental limits of detection (LOD) and quantification (LOQ) of analytes ranged from 0.01-0.72 μg L-1 and 0.05-2.39 μg L-1, respectively, with satisfactory linear calibration (R2 > 0.995) and precision (< 9.9%). Recoveries in spike samples ranged between 77.5-104.9% in pure water, 59.4-97.8% in surface water (SW), and 58.2-108.6% in wastewater effluent (WWE) with relative standard deviations ≤ 12.8%. The matrix effects observed for most analytes were suppression (0-28.1%) except for five analytes having presented enhancement (0-14.6 %) in SW or WWE. This method can basically meet the needs of trace antibiotic residues detection in waters, with examples of concentrations of detected antibiotics being lower than LOQ (LLQ) -94.47 ng L-1 in WWEs and LLQ-15.47 ng L-1 in SW in the lower reaches of the Yangtze River Basin.

Damage to the sinus node (SN) has been described as a potential complication of superior vena cava (SVC) isolation. There have been reports of permanent SN injury requiring pacemaker implantation during isolation of the SVC.It is safe and effective to isolate SVC with the second-generation 28-mm cryoballoon by using a novel method.Forty-three patients (including six redo cases) with SVC-related atrial fibrillation (AF) from a consecutive series of 650 patients who underwent cryoballoon ablation were included. After pulmonary vein isolation was achieved, if the SVC trigger was identified, the SVC was electrically isolated using the cryoballoon. First, the cryoballoon was inflated in the right atrium (RA) and advanced towards the SVC-RA junction. After total occlusion was confirmed by dye injection with total retention of contrast in the SVC, the SVC-RA junction was determined. Next, the cryoballoon was deflated, advanced into SVC, then reinflated, and pulled back gently. The equatorial band of the cryoballoon was then set slightly (4.32 ± 0.71 mm) above the SVC-RA junction for isolation of the SVC.Real-time SVC potential was observed in all patients during ablation. The mean time to isolation was 24.5 ± 10.7 s. The SVC was successfully isolated in all patients. The mean number of freeze cycles was 2.5 ± 1.4 per patient, and the mean ablation time was 99.8 ± 22.7 s. A transient phrenic nerve (PN) injury occurred in one patient (2.33%). There were no SN injuries. Freedom from AF rates at 6 and 12 months was 97.7% and 93.0%, respectively.This novel method for SVC isolation using the cryoballoon is safe and feasible when the SVC driver during AF is determined and could avoid SN injury. PN function should still be carefully monitored during an SVC isolation procedure.

Attribute-based signature (ABS) can provide fine-grained and anonymous authentication for the Industrial Internet of Things (IIoT). However, key exposure and the computational performance bottleneck of resource-constrained devices raise a challenge to the IIoT-oriented ABS schemes. To confront the above challenge, this article proposes an intrusion-resilient server-aided ABS (IR-SA-ABS) scheme. This scheme designs to periodically update the signing key with the assistance of a helper device, and the signing key is refreshed for multiple rounds aperiodically within each time period under the supervision of the helper device. In this way, the system remains secure even if both the helper device and the signing device are compromised. During this process, we significantly reduce the computational overheads of resource-constrained devices by delegating all of the key update and refresh operations and most of the signature generation and verification operations to a powerful server. Subsequently, we present the rigorous security proof of IR-SA-ABS. The comparison and experiment demonstrate the efficiency and practicality of IR-SA-ABS in the IIoT scenario.

Emerin is an inner nuclear envelope protein encoded by the EMD gene, mutations in which cause Emery-Dreifuss muscular dystrophy type 1 (EDMD1). Cardiac involvement has become a major threat to patients with EDMD1; however, the cardiovascular phenotype spectrums of emerinopathy and the mechanisms by which emerin regulates cardiac pathophysiology remain unclear. Here, we identified a novel nonsense mutation (c.C57G, p.Y19X) in the EMD gene in a Han Chinese family through high-throughput sequencing. Two family members were found to have EDMD1 with muscle weakness and cardiac arrhythmia. Mechanistically, we first discovered that knockdown of emerin in HL-1 or H9C2 cardiomyocytes lead to impaired mitochondrial oxidative phosphorylation capacity with downregulation of electron transport chain complex I and IV and upregulation of complex III and V. Moreover, loss of emerin in HL-1 cells resulted in collapsed mitochondrial membrane potential, altered mitochondrial networks and downregulated multiple factors in RNA and protein level, such as PGC1α, DRP1, MFF, MFN2, which are involved in regulation of mitochondrial biogenesis, fission and fusion. Our findings suggest that targeting mitochondrial bioenergetics might be an effective strategy against cardiac disorders caused by EMD mutations.

Background Remote magnetic navigation (RMN)‐guided ablation has become an inspiring method of catheter ablation for tachyarrhythmias. Hypothesis Data from a large‐scale single center may provide further insight into the safety of and the learning curve for RMN‐guided ablation. Methods A total of 1003 catheter ablation procedures using RMN for conditions including supraventricular ventricular tachycardia, atrial tachyarrhythmias, and premature ventricular contraction/ventricular tachycardia (PVC/VT) were retrospectively analyzed from an ablation registry. Procedural outcomes, including procedure time, mapping time, X‐ray time, and RF time, were assessed. The complications were classified into two categories: major and minor. A subanalysis was used to illustrate the learning curve of RMN‐guided ablation by assessing procedure time and total X‐ray time of 502 atrial fibrillation (AF) ablation procedures. Results Among these procedures, 556 (55.4%) were AF and 290 (28.9%) were PVC/VT. Electrical pulmonary vein isolation was achieved in 99.0% of AF procedures, and acute success reached 90.3% in PVC/VT procedures. The overall complication rate was 0.5%. In the subanalysis of AF procedures, the overall procedure time and X‐ray time of procedures were short (125.9 ± 54.6 and 5.3 ± 3.9 minutes, respectively) and proceeded to decrease from the initial 30 procedures to about 300 procedures, where the learning curve reached plateau, demonstrating maximum procedure efficiency. Conclusions RMN‐guided ablation is safe, as verified by very low overall complication rate and reduced X‐ray time. In our study, even the first AF procedures had a relatively low procedure time and total X‐ray time, and procedure efficiency improved during the learning curve.

Background Data comparing dabigatran with rivaroxaban regarding the resolution of left atrial/left atrial appendage (LA/LAA) thrombus in patients with nonvalvular atrial fibrillation (AF) are scarce. This study aimed to compare the efficacy and safety of dabigatran vs rivaroxaban regarding the resolution of LA/LAA thrombus in patients with nonvalvular AF. Methods This retrospective study enrolled nonvalvular AF patients scheduled to undergo catheter ablation or cardioversion in Shanghai Ruijin Hospital between January 2014 and January 2019. Altogether, 34 patients with LA/LAA thrombus detected by transesophageal echocardiography (TEE) were enrolled. Among them, 12 patients were treated with dabigatran 150 mg bid and the other 22 with rivaroxaban 20 mg qd. Follow-up TEE was performed within greater than or equal to 3 weeks to less than 6 months of the initial TEE to evaluate the resolution of the LA/LAA thrombus. Results Baseline patient characteristics were similar in the two groups. Overall, 18 patients (81.8%) in the rivaroxaban group had complete thrombus resolution after 70.3 ± 22.1 treatment days, and 10 patients (83.3%) in the dabigatran group had complete thrombus resolution after 69.3 ± 47.9 treatment days. There was no significant difference between the groups (P = .6). TEE showed that the average length, width, and area of thrombus significantly decreased in both groups after treatment, although there was no significant difference in the amount of change in these parameters between the two groups after treatment (P = .6). Undissolved thrombus in two patients in the rivaroxaban group did dissolve after switching to dabigatran. Conclusions The results suggest that both dabigatran and rivaroxaban are potential options for treating LA/LAA thrombus in patients with nonvalvular AF. Dabigatran could be an alternative option for the resolution of LA/LAA thrombus resistant to rivaroxaban.

Existing server-aided attribute-based signature (SA-ABS) to secure industrial Internet of Things (IIoT)-oriented applications raise challenges such as achieving collusion attack resilience and realizing expressive linear secret-sharing scheme (LSSS) access structures. In this paper, we positively address these challenges by proposing a novel SA-ABS for IIoT. Distinct from the existing works in this field, our SA-ABS protocol not only allows to delegate the heavy calculation in both signature generation and verification to a third-party server, but also resists the collusion attack and realizes expressive LSSS access structures. The formal proof about the unforgeability of the proposed SA-ABS has been given on the basis of the standard model. Theoretical analysis as well as experimental simulation reveal the fact that the proposed SA-ABS is feasible and efficient.

The objective of this study was to assess the impact of steerable sheaths compared with fixed-curve sheaths on the procedural outcomes of atrial fibrillation (AF) ablation guided by robotic magnetic navigation (RMN).In this retrospective case-control study, 110 patients scheduled for AF catheter ablation were enrolled and divided into two groups. Fifty-five patients (paroxysmal, 70%) were treated with RMN-guided ablation utilizing a steerable sheath and another 55 patients (paroxysmal, 70%) were ablated with RMN using a fixed-curve sheath. Clinical characteristics were similar between the two groups. Compared with the fixed-curve sheath group, the steerable sheath group procedure time (111.9 ± 25.2 vs. 90.4 ± 20.7 min, p .001) and radiofrequency (RF) time (35.9 ± 9.0 vs. 30.5 ± 7.4 min, p .001) were significantly shortened. Additionally, the navigation index was significantly improved (0.41 ± 0.06 vs. 0.48 ± 0.08, p .001) in the steerable sheath group. By employing a large catheter loop for targeting the right pulmonary veins (PVs), the steerable sheath group significantly reduced the RF delivery time (15.0 ± 3.0 vs. 12.0 ± 2.1 min, p .001) during right-side PV isolation (PVI). However, total fluoroscopy time was similar between the two groups (5.6 ± 2.6 vs. 5.0 ± 2.0 min, p .05). Acute PVI success rates were similar between the two groups. No major or minor complications occurred in either group.Appropriate utilization of steerable sheath technology can improve the efficiency of AF ablation guided by RMN, primarily by reducing the total procedure and RF delivery times of right-side PVI without compromising safety.

For novice operators, mastering catheter ablation of left-sided accessory pathway (LSAP) in a short duration of time without compromising efficacy and safety remains a challenge. In this study an attempt to shorten the learning curve by using robotics via a remote magnetic navigation (RMN) system was performed.Novice physician fellows without prior catheter ablation experience initiated their process of learning LSAP ablation using the Niobe™ RMN system. Their procedure parameters were recorded and compared with experienced operators using RMN and manual catheter navigation (MCN).Novice operators quickly shortened the total procedure time after their first five procedures. In subsequent procedures, no significant difference in procedure time, fluoroscopy exposure or ablation time was observed between novice and experienced RMN operators. When compared to MCN operators, novice operators avoided excessive radiation exposure beginning with their first RMN procedure, while lower fluoroscopy doses were noted after five procedures. It was observed that procedure parameters did not differ significantly according to LSAP location.The RMN system is a practical and easy to use tool for novice electrophysiology operators to quickly master LSAP ablation, without compromising efficacy or safety. Additionally, when compared to MCN it also protects the operators and patients from excessive radiation exposure during the procedure.

The cloud-assisted medical Internet of Things (MIoT) has played a revolutionary role in promoting the quality of public medical services. However, the practical deployment of cloud-assisted MIoT in an open healthcare scenario raises the concern on data security and user's privacy. Despite endeavors by academic and industrial community to eliminate this concern by cryptographic methods, resource-constrained devices in MIoT may be subject to the heavy computational overheads of cryptographic computations. To address this issue, this paper proposes an efficient, revocable, privacy-preserving fine-grained data sharing with keyword search (ERPF-DS-KS) scheme, which realizes the efficient and fine-grained access control and ciphertext keyword search, and enables the flexible indirect revocation to malicious data users. A pseudo identity-based signature mechanism is designed to provide the data authenticity. We analyze the security properties of our proposed scheme, and via the theoretical comparison and experimental results we demonstrate that for the resource-constrained devices in the patient and doctor side of MIoT, in comparison with other related schemes, ERPF-DS-KS just consumes the lightweight and constant size communication/storage as well as computational time cost. For the keyword search, compared with related schemes, the cloud can quickly check whether a ciphertext contains the specified keyword with slight computations in the online phase. This further demonstrates that ERPF-DS-KS is efficient and practical in the cloud-assisted MIoT scenario.

The exponential increase in the number of genomes deposited in public databases can help us gain a more holistic understanding of the phylogeny and epidemiology of Klebsiella pneumoniae. However, inferring the evolutionary relationships of K. pneumoniae based on big genomic data is challenging for existing methods. In this study, core genes of K. pneumoniae were determined and analysed in terms of differences in GC content, mutation rate, size, and potential functions. We then developed a stable genes-based method for big data analysis and compared it with existing methods. Our new method achieved a higher resolution phylogenetic analysis of K. pneumoniae. Using this genes-based method, we explored global phylogenetic relationships based on a public database of nearly 953 genomes. The results provide useful information to facilitate the phylogenetic and epidemiological analysis of K. pneumoniae, and the findings are relevant for security applications.

A fully automated solid-phase extraction (SPE) coupled ultra-high-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed for analysis of antibiotics (sulfonamides, quinolones, and macrolide) in water matrices. Sample preparation optimization included the selection of the best SPE material and configuration (HLB disks), sample volume (500−1000 mL water sample (pH = 3)) with a flow rate at 1−2 mL min− 1, and an elution procedure with 2 ⋅ 6 mL methanol, 2 ⋅ 6 mL acetone-methanol (V/V = 1/1). Meanwhile, the parameters for UPLC-MS/S detection of each analyte was optimized, including LC retention time, and MS parameters. The instrumental limits of detection (LOD) and quantification (LOQ) of analytes ranged from 0.01−0.72 µg L− 1 and 0.05−2.39 µg L− 1, respectively, with good linear correlation (R2 > 0.995) and precision (− 1 in WWEs and BQL−15.47 ng L− 1 in SW in the lower reaches of the Yangtze River Basin.

Severe left atrial spontaneous echo contrast (SLASEC) is considered the prior stage to thrombosis and a high-risk factor for thrombotic events. Studies have suggested an effect of D-dimer blood concentration on exclusion of left atrial thrombus (LAT), but it remains unclear whether D-dimer concentrations differ between atrial fibrillation (AF) patients with SLASEC or LAT. Nonvalvular AF patients scheduled to undergo catheter ablation or cardioversion in Shanghai Ruijin Hospital between January 2017 and July 2020 were screened for this prospective study. All patients underwent transesophageal echocardiography (TEE) to detect SLASEC or LAT. D-dimer concentrations were measured at the time of TEE. Clinical data including CHA2DS2-VASc score were evaluated. Major complications with thromboembolism in the SLASEC group were followed up at least 6 months after therapy. Among 920 consecutively enrolled nonvalvular AF patients, 30 patients with SEC grade 0, 35 patients with SLASEC, and 22 patients with LAT were included. D-dimer concentration and CHA2DS2-VASc score were significantly lower in the SLASEC group compared with the LAT group (D-dimer, 0.26±0.13 vs. 0.86±0.9 mg/L, P

Background Idiopathic ventricular arrhythmias (IVAs) with right bundle branch block (RBBB) and superior axis commonly originate from posterior mitral annulus (PMA), the left ventricular (LV) posterior fascicle (LPF), and the LV posterior papillary muscles (PPM). Hypothesis Remote magnetic navigation (RMN)‐guided ablation might be safe and effective for these three origins of IVAs. Methods Thirty consecutive IVA patients with RBBB and superior axis (11 MPA‐IVAs, 11 LPF‐IVAs, and 8 PPM‐IVAs) were included in this study. Electrical mapping and ablation with RMN were performed in the LV through a trans‐septal approach. Navigation index, defined as the ratio of total radiofrequency (RF) time and the time from first burn to last burn, was used to determine the efficiency of RMN‐guided ablation. Results The overall acute success rate was achieved in 93% (PMA, 100%; LPF, 91%; PPM, 88%; p > 0.05). No complication occurred in this study. The procedure time of PPM‐IVAs group was 34 and 14 min longer when compared with MPA‐IVAs and LPF‐IVAs group, respectively, without an increase of X‐ray time. The mean navigation index was 0.45 ± 0.20. The PPM‐IVAs group had an underperforming navigation index value (0.29 ± 0.11) (p

Navitoclax, which is a type of senolytic drug, selectively eliminates senescent cells. This study aimed to evaluate the therapeutic potential of navitoclax in treatment of angiotensin II (Ang II)-induced heart failure in mice. Navitoclax or vehicle was administrated in mice with Ang II-induced heart failure. Cardiac function and electrophysiology were assessed before and after administration of navitoclax. Cardiac remodeling, including morphological changes, fibrosis, and inflammatory responses, was analyzed in myocardial tissue. Cellular effects of navitoclax were validated in isolated primary cardiomyocytes and cardiac fibroblasts in vitro. Echocardiography of mice showed that navitoclax improved cardiac dysfunction by improving the left ventricular ejection fraction (vehicle: 45.88 ± 2.19%; navitoclax: 54.70 ± 1.65%, P < 0.01). In cardiac electrophysiological testing, navitoclax increased conduction velocity (vehicle: 1.37 ± 0.05 mm/ms; navitoclax: 1.69 ± 0.08 mm/ms, P < 0.05) and decreased susceptibility to ventricular tachyarrhythmia induced by programmed electrical stimulation. Histopathological staining, immunofluorescence, and western blotting examinations showed that navitoclax ameliorated Ang II-induced cardiac fibrosis, hypertrophy, and the inflammatory response. Moreover, navitoclax eliminated senescent cells by inducing apoptosis. Therefore, navitoclax improved cardiac function and electrophysiological characteristics through decreasing cardiac fibrosis, hypertrophy, and inflammation in mice with heart failure. Pharmacological clearance of senescent cells may be a potential therapeutic approach in heart failure with reduced ejection fraction.

Insulator equipment is an important part of the transmission line of the power grid. It can play a good insulation role among the conductor, the crossbar and the tower. Whether the insulator can work normally directly affects the stable operation of the power grid. To this end, for the transmission line insulator images acquired by drones or robots, an online recognition and defect diagnosis model of transmission line insulators based on YOLOv3 network is proposed. By training YOLOv3 network, the characteristics of various insulators under complex backgrounds are learned and accurately recognized, and combined with particle filter algorithm for defect diagnosis of insulators in various states. The simulation results of the transmission line inspection image show that the proposed automatic insulator identification and defect diagnosis method can quickly and accurately identify the insulator from the transmission line inspection image, and diagnose whether the insulator is damaged and the position of the defect, which is beneficial to improve the transmission line Intelligent inspection level.

Introduction: Previous genome-wide studies have identified an association between the rs2106261 single-nucleotide polymorphism (SNP) in the zinc finger homeobox 3 (ZFHX3) gene and an increased risk of atrial fibrillation (AF). However, this association remains controversial, since conflicting results have been reported in previous studies. We aimed to investigate the association between the ZFHX3 rs2106261 polymorphism and susceptibility to AF. Methods: A comprehensive literature search, of articles written in either English or Chinese, was conducted on various databases, including PubMed, Embase, Web of Science, the Cochrane library, Wan Fang, and CNKI, for studies performed up to August 1, 2020. Data were abstracted and pooled using Stata 14.0 software. A meta-analysis was performed on all selected studies based on ZFHX3 rs2106261 polymorphism genotypes. Results: Nine studies, including 10,107 cases and 58,663 controls, were analyzed in the meta-analysis. In the overall population, a significant association was found between AF and the T-allelic ZFHX 3 rs2106261 SNP (odds ratio [OR] = 1.32, 95% confidence interval [CI] 1.19–1.46). In subgroup analysis, a significant association between the T-allele of rs7193343 and risk of AF in Caucasian (OR = 1.23, 95% CI 1.10–1.37) and Asian subgroups (OR = 1.58, 95% CI 1.32–1.89) was observed. However, no statistically significant association was found in African populations (OR = 1.06, 95% CI 0.95–1.19). Conclusion: The genetic variant rs2106261 SNP is associated with susceptibility to AF in Caucasian and Asian individuals, with Asian samples showing a stronger association. However, based on the current evidence, no association was found in African samples. Future studies, with larger sample sizes and multiple ethnicities, are still necessary.

The occurrence of 26 antibiotics from three groups of Sulfonamides, Quinolones and Macrolides were investigated in the surface water of Pudong New Area, Shanghai in March (dry season) and June (wet season). As a result, the detection rates of the three groups were 20%, 81% and 56% (n = 10) with the concentration range of not detected-9.73 ng L-1, 30-344 ng L-1, and 14-107 ng L-1, respectively. Comparably, during wet season, the detection rates were 20%, 56% and 25% with the range of ND-14 ng L-1, 32-92 ng L-1, and ND-22 ng L-1, respectively. This indicates higher concentrations in dry season than that in wet season, which was attributed to the water dilution and weaker self-purification of the river during dry season. In addition, significant correlations were observed between SMA and most of Quinolones during dry season, and Quinolones and Macrolides during wet season, due to the similar sources. Considering for the typical wastewater sources in the investigated area, Quinolones were identified to be the most significant group in the aquiculture water. Furthermore, pharmaceutical manufacturing factory (PMF) and sewage treatment plant (STP) should be the serious point source pollution as the concentration in their effluents could range from ng L-1 to mg L-1. The occurrence and fate of antibiotics in the aquatic system of Pudong New Area need to be paid more attention to prevent the potential risk for human beings in the future study.

Electron beam (EB) has proven to be an effective advanced oxidation reduction process (AORP) to degrade the psychiatric drug carbamazepine (CBZ); however, the degradation mechanism and the toxicity of the final reaction solutions to aquatic microorganisms needed further investigation. In this study, CBZ was eventually degraded and even mineralized by EB treatment, where the degradation of CBZ followed the pseudo-first-order kinetics with R2 > 0.98. Acidic conditions, presence of an additional oxidant (2.5 mmol L−1 H2O2), and O2/air-saturated conditions improved the degradation efficiency of CBZ, as well as the radiation chemical yield (G-value defined as the efficiency of the irradiation process). Concentrations of transient reactive species (TRS) caused by EB were quantified under different conditions at doses of 0.956 and 3.17 kGy, and the apparent quantum yield of CBZ degradation was in the order of OH > H > eaq−. However, the contribution of these species to CBZ degradation was in the order of OH > eaq− > H due to the generation of only a small amount of H. Findings regarding the changes of in CBZ degradation intermediates, short-chain fatty acids (SCFAs), and total organic carbon showed that CBZ can gradually be mineralized into CO2/CO32−, H2O, and NH3/NH4+ by the EB process. Additionally, an excellent rotifer survival rate after 5-day culturing in the reaction solutions resulting from 5-kGy treatment indicated that EB can be a safe AORP to mineralize CBZ in solution. These findings provide scientific proof for the EB being an effective AORP for removal of psychiatric drugs from aqueous solutions, laying the foundation for future remediation research.

Introduction Catheter ablation of frequent para-Hisian premature ventricular contractions (PH-PVCs) is considered to be challenging. The purpose of this study was to evaluate the strategy, potential technical advantages, and clinical outcomes of remote magnetic navigation (RMN) in the ablation of PH-PVCs. Methods Fifteen consecutive patients with PH-PVCs were included in this study. Electrical mapping was initially performed in the right ventricular septum by manipulating the RMN catheter with a "U-curve." In the case of no optimal ablation site or ablation failure, the ablation catheter was directed to the left ventricular (LV) septum through a transseptal approach for further mapping and ablation by manipulating the RMN catheter with a "reverse S-curve." Results Nine of 15 patients were submitted to ablation on the right side. However, ablation success was only achieved in only three (33%) cases. Of the other 12 patients, 11 underwent LV mapping and ablation. In this subset, 9 of 11 (82%) PH-PVCs were totally eliminated on the left side. Overall, RMN-guided mapping and ablation successfully eliminated 12 (80%) of 15 idiopathic PH-PVCs. During follow-up, the reoccurrence of PVCs was reported in 1 (8%) of 12 patients. No atrioventricular block was observed during or after the procedure. Conclusion RMN-guided catheter ablation for PH-PVCs is effective and safe in unselected patients. Due to the excellent reachability and contact with special morphologies of the RMN catheter on both sides of the ventricular septum, RMN can be considered an effective approach for frequent PH-PVCs.

The occurrence and fate of five endocrine disrupting chemicals (EDCs), including nonylphenol (NP), 4-tert-octylphenol (4-t-OP), 4-tert-butylphenol (4-t-BP), bisphenol A (BPA) and norethindrone (NET) was investigated in four wastewater treatment plants (WWTPs) and receiving river (Suzhou River and Yangtze River) of Shanghai. Selected EDCs in WWTPs influents ranged from 1.02 to 3560 ng L−1, which dominated by NP and BPA. Target compounds detected in effluents were from N.D. to 1136 ng L−1, with NP as most prevalent. The removal rates of target compounds varied from negative of NET to 99 % of BPA. Except of NET, efficiently removal rates (>70 %) were observed in WWTPs. Biological treatment was the major removal stage of selected EDCs in WWTPs. Furthermore, the selected EDCs were detected from N.D. to 424 ng L−1 in receiving river. The correlation analysis suggested EDCs pollution in receiving river might be mainly contributed by WWTPs effluents. The risk quotient of NP (RQ > 1) was higher than any other pollutants, indicating its relatively higher potential risk for the aquatic organism. These results will provide significant background data to future EDCs pollution control and management in Shanghai, China.

Laser balloon (LB) and cryoballoon (CB) ablation are two balloon-based catheter ablation technologies used for atrial fibrillation (AF) ablation in recent years. However, the efficacy and the safety of LB ablation in comparison to CB ablation remained indeterminate. We sought to compare these two technologies by conducting meta-analysis of previous studies using both the CB and LB ablation systems for AF ablation. We searched electronic scientific databases for studies of LB vs. CB ablation in AF patients. The procedural efficacy was assessed by the success of acute pulmonary vein isolation (PVI) and the 12-month recurrence of any atrial arrhythmia, and the safety was evaluated by the risk of procedure-related complications. A total of 595 participants (LB, n = 292 vs. CB, n = 303) from eight studies were included in this meta-analysis. Risk of acute PVI failure (risk ratio, RR 95% confidence interval [95% CI] = 2.55 [0.86–7.56], P = 0.09) and atrial arrhythmia recurrence in 12 months (RR [95% CI] = 0.91 [0.64–1.28], P = 0.59) were comparable between LB vs. CB ablation, and LB ablation tended to be more effective than CB ablation in paroxysmal AF patients (RR [95% CI] = 0.70 [0.47–1.03], P = 0.07). Risk of procedure-related complications was similar while LB ablation showed slightly higher risk without statistic significance (LB 13.9% vs. CB 9.3%, RR [95% CI] = 1.52 [0.88–2.64], P = 0.14). Compared with CB ablation, LB ablation led to longer procedure duration (weighted mean differences WMD [95% CI] =29.7 [15.8–43.7], P

Background— Mutations in SCN2B , encoding voltage-gated sodium channel β2-subunits, are associated with human cardiac arrhythmias, including atrial fibrillation and Brugada syndrome. Because of this, we propose that β2-subunits play critical roles in the establishment or maintenance of normal cardiac electric activity in vivo. Methods and Results— To understand the pathophysiological roles of β2 in the heart, we investigated the cardiac phenotype of Scn2b null mice. We observed reduced sodium and potassium current densities in ventricular myocytes, as well as conduction slowing in the right ventricular outflow tract region. Functional reentry, resulting from the interplay between slowed conduction, prolonged repolarization, and increased incidence of premature ventricular complexes, was found to underlie the mechanism of spontaneous polymorphic ventricular tachycardia. Scn5a transcript levels were similar in Scn2b null and wild-type ventricles, as were levels of Na v 1.5 protein, suggesting that similar to the previous work in neurons, the major function of β2-subunits in the ventricle is to chaperone voltage-gated sodium channel α-subunits to the plasma membrane. Interestingly, Scn2b deletion resulted in region-specific effects in the heart. Scn2b null atria had normal levels of sodium current density compared with wild type. Scn2b null hearts were more susceptible to atrial fibrillation, had increased levels of fibrosis, and higher repolarization dispersion than wild-type littermates. Conclusions— Genetic deletion of Scn2b in mice results in ventricular and atrial arrhythmias, consistent with reported SCN2B mutations in human patients.

Rationale: Compelling data indicate that excessive Ca2+ leak from the sarcoplasmic reticulum (SR) contribute to atrial fibrillation (AF) pathogenesis. However, the role of RyR2 phosphorylation in Ca2+ leak in particular and cardiac diseases in general remains controversial. Aim: To investigate the effect of genetic inhibition of two major RyR2 phosphorylation sites on the channel function and atrial arrhythmogenesis. Methods and Results: We performed programmed electrical stimulation in anesthetized wild type (WT) mice and in mice harboring two RyR2 mutations that prevent PKA and CaMKII phosphorylation (S2808A and S2814A, respectively). Surprisingly, the double knock-in (DKI) mice exhibited increased incidence of AF episodes (5.2±3% WT vs 45±5% DKI, p

In this study, 14 polybrominated diphenyl ethers (PBDEs) congeners were investigated in soil and outdoor dust taken from Jiading District, Shanghai City. The concentrations of Σ13PBDEs (BDE-17, BDE-28, BDE-47, BDE-66, BDE-71, BDE-85, BDE-99, BDE-100, BDE-138, BDE-153, BDE-154, BDE-183 and BDE-190) and BDE-209 ranged from 0.37 to 32.9ngg(-1) and 4.31 to 141.8ngg(-1) dry weight (dw) in soil. Concentrations in outdoor dust ranged from 1.03 to 112.5ngg(-1) and 6.71 to 342.1ngg(-1) (dw) for Σ13PBDEs and BDE-209. BDE-209 was the predominant congener both in soil and outdoor dust, but the BDE-209 contribution was much lower in dust compared with that in soil. A significant correlation between PBDEs congeners and specific land use type was observed, and principal component analysis (PCA) revealed that the major source of PBDE in samples was associated with prevalent use of technical Deca-BDE, which also suggested the contributions from Penta-BDE and Octa-BDE mixtures. Canonical correlation analysis suggested the two sets of PBDEs data (soil and outdoor dust) were uncorrelated, and Spearman correlation coefficient matrix implied that the degradation pathways of PBDEs were different between soil and outdoor dust.

Steady-state radiolysis experiments were performed to look into the decomposition and primary radiolytic degradation mechanism of electron beam (EB) -- irradiation nonylphenol (NP), which might be useful for the application of radiation for treating alkyl phenol-laden wastewaters. The study illustrated that the decomposition of NP in a methanol/water reduction system is higher than in an acetonitrile/water oxidation system and in an acetone/water system. This appears to be due to both •OH and eaq-playing a role in the NP degradation, although the latter is more effective. The degradation rate of NP enhanced with decreasing initial concentration at a constant absorbed dose in a methanol/water solution. Finally, a preliminary investigation of the reaction mechanism under reduction system suggested that the initial products of the reaction were ethyl benzene and icycle[4.2.0]octa-1, 3, 5-triene, which arise from eaq-attack at the position of the alkyl side chain of NP.

Scn1b-null mice have a severe neurological and cardiac phenotype. Human mutations inSCN1Bresult in epilepsy and cardiac arrhythmia.SCN1Bis expressed as two developmentally regulated splice variants, β1 and β1B, that are each expressed in brain and heart in rodents and humans. Here, we studied the structure and function of β1B and investigated a novel humanSCN1Bepilepsy-related mutation (p.G257R) unique to β1B. We show that wild-type β1B is not a transmembrane protein, but a soluble protein expressed predominantly during embryonic development that promotes neurite outgrowth. Association of β1B with voltage-gated Na+channels Nav1.1 or Nav1.3 is not detectable by immunoprecipitation and β1B does not affect Nav1.3 cell surface expression as measured by [3H]saxitoxin binding. However, β1B coexpression results in subtle alteration of Nav1.3 currents in transfected cells, suggesting that β1B may modulate Na+current in brain. Similar to the previously characterized p.R125C mutation, p.G257R results in intracellular retention of β1B, generating a functional null allele. In contrast, two otherSCN1Bmutations associated with epilepsy, p.C121W and p.R85H, are expressed at the cell surface. We propose that β1B p.G257R may contribute to epilepsy through a mechanism that includes intracellular retention resulting in aberrant neuronal pathfinding.