Application of a circular-shaped pulsed field ablation catheter with magnetic sensors for pulmonary vein isolation: a multi-centre clinical study report.

AIMS: A few studies have reported the effect and safety of pulsed field ablation (PFA) catheters for ablating atrial fibrillation (AF), which were mainly based on basket-shaped or flower-shaped designs. However, the clinical application of a circular-shaped multi-electrode catheter with magnetic sensors is very limited. To study the efficacy and safety of a PFA system in patients with paroxysmal AF using a circular-shaped multi-electrode catheter equipped with magnetic sensors for pulmonary vein isolation (PVI). METHODS AND RESULTS: A novel proprietary bipolar PFA system was used for PVI, which utilized a circular-shaped multi-electrode catheter with magnetic sensors and allowed for three-dimensional model reconstruction, mapping, and ablation in one map. To evaluate the efficacy, efficiency, and safety of this PFA system, a prospective, multi-centre, single-armed, pre-market clinical study was performed. From July 2021 to December 2022, 151 patients with paroxysmal AF were included and underwent PVI. The study examined procedure time, immediate success rate, procedural success rate at 12 months, and relevant complications. In all 151 patients, all the pulmonary veins were acutely isolated using the studied system. Pulsed field ablation delivery was 78.4 ± 41.8 times and 31.3 ± 16.7 ms per patient. Skin-to-skin procedure time was 74.2 ± 29.8 min, and fluoroscopy time was 13.1 ± 7.6 min. The initial 11 (7.2%) cases underwent procedures with deep sedation anaesthesia, and the following cases underwent local anaesthesia. In the initial 11 cases, 4 cases (36.4%) presented transient vagal responses, and the rest were all successfully preventatively treated with atropine injection and rapid fluid infusion. No severe complications were found during or after the procedure. During follow-up, 3 cases experienced atrial flutter, and 11 cases had AF recurrence. The estimated 12-month Kaplan-Meier of freedom from arrhythmia was 88.4%. CONCLUSION: The PFA system, comprised of a circular PFA catheter with magnetic sensors, could rapidly achieve PVI under three-dimensional guidance and demonstrated excellent safety with comparable effects.

Changes of ubiquitylated proteins in atrial fibrillation associated with heart valve disease: proteomics in human left atrial appendage tissue.

Background: Correlations between posttranslational modifications and atrial fibrillation (AF) have been demonstrated in recent studies. However, it is still unclear whether and how ubiquitylated proteins relate to AF in the left atrial appendage of patients with AF and valvular heart disease. Methods: Through LC-MS/MS analyses, we performed a study on tissues from eighteen subjects (9 with sinus rhythm and 9 with AF) who underwent cardiac valvular surgery. Specifically, we explored the ubiquitination profiles of left atrial appendage samples. Results: In summary, after the quantification ratios for the upregulated and downregulated ubiquitination cutoff values were set at >1.5 and <1:1.5, respectively, a total of 271 sites in 162 proteins exhibiting upregulated ubiquitination and 467 sites in 156 proteins exhibiting downregulated ubiquitination were identified. The ubiquitylated proteins in the AF samples were enriched in proteins associated with ribosomes, hypertrophic cardiomyopathy (HCM), glycolysis, and endocytosis. Conclusions: Our findings can be used to clarify differences in the ubiquitination levels of ribosome-related and HCM-related proteins, especially titin (TTN) and myosin heavy chain 6 (MYH6), in patients with AF, and therefore, regulating ubiquitination may be a feasible strategy for AF.

Non-fasting changes of Hs-CRP level in Chinese patients with coronary heart disease after a daily meal.

High-sensitivity C-reactive protein (hs-CRP) is a key inflammatory factor in atherosclerotic cardiovascular diseases. In Chinese patients with coronary heart disease (CHD), the changes in hs-CRP levels after a daily meal and the effect of statins on those were never explored. A total of 300 inpatients with CHD were included in this study. Hs-CRP levels were measured in the fasting and non-fasting states at 2 h and 4 h after a daily breakfast. All inpatients were divided into two groups according to fasting hs-CRP ≤ 3 mg/L or not. Group with fasting hs-CRP ≤ 3 mg/L had a significantly higher percentage of patients with statins using ≥ 1 month (m) before admission than that with fasting hs-CRP > 3 mg/L (51.4% vs. 23.9%, P < 0.05). Hs-CRP levels increased significantly in the non-fasting state in two groups (P < 0.05). About 32% of patients with non-fasting hs-CRP > 3 mg/L came from those with fasting hs-CRP ≤ 3 mg/L. In conclusion, hs-CRP levels increased significantly in CHD patients after a daily meal. It suggested that the non-fasting hs-CRP level could be a better parameter to evaluate the inflammation state of CHD patients rather than fasting hs-CRP level.

Simple Synthesis of Red Iridium(III) Complexes with Sulfur-Contained Four-Membered Ancillary Ligands for OLEDs.

Phosphorescent iridium(III) complexes have been widely researched for the fabrication of efficient organic light-emitting diodes (OLEDs). In this work, three red Ir(III) complexes named Ir-1, Ir-2, and Ir-3, with Ir-S-C-S four-membered framework rings, were synthesized efficiently at room temperature within 5 min using sulfur-containing ancillary ligands with electron-donating groups of 9,10-dihydro-9,9-dimethylacridine, phenoxazine, and phenothiazine, respectively. Due to the same main ligand of 4-(4-(trifluoromethyl)phenyl)quinazoline, all Ir(III) complexes showed similar photoluminescence emissions at 622, 619, and 622 nm with phosphorescence quantum yields of 35.4%, 50.4%, and 52.8%, respectively. OLEDs employing these complexes as emitters with the structure of ITO (indium tin oxide)/HAT-CN (dipyra-zino[2,3-f,2',3'-h]quinoxaline-2,3,6,7,10,11-hexacarbonitrile, 5 nm)/TAPC (4,4'-cyclohexylidenebis[N,N-bis-(4-methylphenyl)aniline], 40 nm)/TCTA (4,4″,4″-tris(carbazol-9-yl)triphenylamine, 10 nm)/Ir(III) complex (10 wt%): 2,6DCzPPy (2,6-bis-(3-(carbazol-9-yl)phenyl)pyridine, 10 nm)/TmPyPB (1,3,5-tri(mpyrid-3-yl-phenyl)benzene, 50 nm)/LiF (1 nm)/Al (100 nm) achieved good performance. In particular, the device based on complex Ir-3 with the phenothiazine unit showed the best performance with a maximum brightness of 22,480 cd m-2, a maximum current efficiency of 23.71 cd A-1, and a maximum external quantum efficiency of 18.1%. The research results suggest the Ir(III) complexes with a four-membered ring Ir-S-C-S backbone provide ideas for the rapid preparation of Ir(III) complexes for OLEDs.

Ladder-Type Dye with Large Transition Dipole Moment for Solvatochromism and Microphase Visualization.

A large transition dipole moment is usually pursued by strategies of twisted intramolecular charge transfer (TICT) or planar intramolecular charge transfer (PICT) to obtain obvious Stokes shifts and dramatic color changes with tuning of polarities. However, both strategies have their drawbacks and suffer from fluorescence quenching in solid states. Herein, a ladder-type molecule ISOAA-H with an intramolecular hydrogen bond is designed, which undergoes intramolecular charge transfer and proton shift to harvest a large transition dipole moment under light irradiation. Thanks to its out-of-plane side chains, the intermolecular π-π stacking of backbones is prohibited and solid emission is generated. ISOAA-H exhibits outstanding solvatochromic behavior with polarity changes of solvents or polymer matrixes and is successfully used to detect the microphase separation of polymer blends. These results indicate that a strategy combining the advantages of TICT and PICT is established for environment-sensitive dyes used in both solution and solid state.

[Microplastic Pollution of the Beaches in Xiamen Bay, China].

Microplastics are tiny ubiquitous plastic particles smaller than five millimeters (5 mm) in size. Coastal and bay areas are constantly under continuous and increasing pressure from the activities of humans. Microplastic pollution is now recognized as a great threat to these areas. This study was designed to understand the microplastic pollution of the beaches in Xiamen Bay. The results showed that microplastic abundance was from (28.1±9.4) to (312.7±35.2) n·kg-1. Four main types of microplastics were identified in Xiamen Bay, including fragments, foams, thin films, and fibers. Of the particles analyzed, over 80% were predominantly microplastic fragments and foam, while the films and fiber microplastics accounted for less than 20% of the particles. Studies on the particle size of microplastics also indicated that the microplastics with particle size less than 1 mm accounted for over 60% of the total microparticles, and the abundance of microplastics trend to decrease with increase in the particle size. Fourier transform infrared spectroscopy analysis demonstrated that the major component of the fragments and fibers was identified as polyethylene, and that of foams and films was identified as polystyrene. The scanning electron microscope studies showed that the microplastics presented obvious signs of cracks. In general, Xiamen Bay beach microplastic pollution is at a lower middle level, and land source pollution is the main source of the microplastic pollution.

MicroRNA-363 inhibits angiogenesis, proliferation, invasion, and migration of renal cell carcinoma via inactivation of the Janus tyrosine kinases 2-signal transducers and activators of transcription 3 axis by suppressing growth hormone receptor gene.

Renal cell carcinoma (RCC) is the most common malignancy involving the kidneys and a major cause of cancer mortality. The involvement of microRNA (miRNA) expression in the tumorigenesis and progression of RCC has been previously highlighted. Therefore, we conducted this study to investigate whether microRNA-363 (miR-363) affects the development of RCC via the Janus tyrosine kinases (JAK2)-signal transducers and activators of transcription (STAT) axis by targeting the growth hormone receptor (GHR), by observing the changes that occurred in the RCC and the normal adjacent tissues of patients with RCC. RCC cells were transfected with a series of miR-363 mimic, miR-363 inhibitor, or small interfering RNA against GHR to determine the influence of miR-363 on the expression of GHR and JAK2-STAT3 axis-related genes with the use of reverse transcription quantitative polymerase chain reaction and Western blot analysis. The angiogenesis, viability, invasion, and migration of cells were evaluated by means of in vitro angiogenesis, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), wound-healing, and Transwell assays. The results revealed reduced miR-363 expression and elevated GHR expression in RCC. It was also found that miR-363 altered the activation of the JAK2-STAT3 axis through the inhibition of GHR. Cells treated with the miR-363 inhibitor presented with increased capillary vessels, cell viability, invasion, and migration, whereas it was on the contrary in the RCC cells with overexpressed miR-363. These results implicated that the overexpression of miR-363 could specifically bind to GHR to downregulate the expression of GHR, which, in turn, inactivates the JAK2-STAT3 axis, thereby influencing the angiogenesis, cell invasion, and migration abilities in RCC.

The association between metabolic syndrome and bladder cancer susceptibility and prognosis: an updated comprehensive evidence synthesis of 95 observational studies involving 97,795,299 subjects.

BACKGROUND: The association between metabolic syndrome (MS) and bladder cancer (BC) was not fully investigated, and most primary studies and pooled analyses were only focused on certain specific components. OBJECTIVE: To further investigate this issue and obtain more precise findings, we conducted this updated evidence synthesis of published studies, which involved not only MS components but also the MS in its entirety. MATERIALS AND METHODS: We searched the PubMed, EMBASE, and Web of Science databases for observational studies on the association between BC susceptibility and/or mortality, and MS and its components. We extracted data from included studies, evaluated heterogeneity, and performed meta-analytic quantitative syntheses. RESULTS: A total of 95 studies with 97,795,299 subjects were included in the present study. According to the results, MS significantly increased the risk of BC (risk ratio [RR]=1.11, 95% CI=1.00-1.23); diabetes significantly increased the risk of BC (RR=1.29, 95% CI=1.19-1.39) and associated with poor survival (RR=1.24, 95% CI=1.08-1.43). Excessive body weight was associated with increased susceptibility (RR=1.07, 95% CI=1.02-1.12), recurrence (RR=1.46, 95% CI=1.18-1.81), and mortality (RR=1.17, 95% CI=1.00-1.37). As indicated by cumulative meta-analysis, sample size was inadequate for the association between BC susceptibility and MS, the association between BC recurrence and excessive body weight, and the association between BC survival and diabetes. The sample size of the meta-analysis was enough to reach a stable pooled effect for other associations. CONCLUSION: Diabetes and excessive body weight as components of MS are associated with increased susceptibility and poor prognosis of BC. Uncertainty remains concerning the impact of overall MS, hypertension, and dyslipidemia on BC susceptibility and prognosis, for which further investigations are needed.

Protective effects of hydrogen sulfide against angiotensin II-induced endoplasmic reticulum stress in HUVECs.

The inhibitory effects of hydrogen sulfide (H2S) on angiotensin II (AngII)-stimulated human umbilical vein endothelial cell (HUVEC) dysfunction remain to be elucidated. Endoplasmic reticulum (ER) stress has been detected in endothelial dysfunction (ED). The present study aimed to determine whether H2S may exert an inhibitory effect on AngII­induced ER stress. Using HUVECs as a model system, the present study used western blotting to detect protein expression, intracellular reactive oxygen species (ROS) levels were determined by oxidative conversion of cell permeable DCFH­DA to fluorescent dichlorofluorescein, CCK­8 assay was used to investigate the cell viability, methylene blue was used to investigate the CSE activity, TUNEL was used to investigate the cells apoptosis. The present study demonstrated that AngII not only upregulated the expression levels of inducible nitric oxide synthase (iNOS), stimulated ROS production and increased cell apoptosis, but also downregulated the expression levels of phosphorylated­endothelial nitric oxide synthase, decreased the expression and activity of cystathionine­c­lyase (CSE) and decreased cell viability. Furthermore, hydrogen peroxide (H2O2; an exogenous ROS) downregulated the expression and activity of CSE, and had similar effects as AngII, whereas the inhibitory effects of AngII were completely suppressed by N-acetyl-L-cysteine (a ROS scavenger). In addition, AngII induced the expression of glucose­regulated protein 78 (GRPP78) and C/EBP homologous protein (CHOP), which are markers of ER stress. Conversely, the stimulatory effects of AngII were completely inhibited by sodium hydrosulfide (NaHS; a H2S donor). Treatment with NaHS attenuated ROS production, inhibited CHOP and GRP78 expression, and decreased cell apoptosis. The present study indicated that AngII induced ED via the activation of ER stress in HUVECs. In addition, the effects of AngII on ER stress could be suppressed by H2S.

Hydrogen sulfide suppresses angiotensin II-stimulated endothelin-1 generation and subsequent cytotoxicity-induced endoplasmic reticulum stress in endothelial cells via NF-κB.

The effects of hydrogen sulfide (H2S) and the nuclear factor κB (NF-κB) signaling pathway in angiotensin II (AngII)-induced endothelin-1 (ET-1) expression and subsequent cytotoxicity remain unclear. The present study aimed to investigate the hypothesis that H2S protects human umbilical vein endothelial cells (HUVECs) against AngII­stimulated ET­1 generation and subsequent cytotoxicity­induced endoplasmic reticulum stress via the NF­κB signaling pathway. The results of the present study demonstrated that AngII significantly upregulated the expression levels of ET­1, glucose­regulated protein 78, CCAAT­enhancer­binding protein homologous protein, phosphorylated (p)­p65 and inducible nitric oxide synthase; stimulated nitric oxide production; suppressed the expression and activity of cystathionine-γ-lyase (CSE), a H2S synthetase; and decreased cell viability. Conversely, BQ788 (an ET­1 receptor antagonist) exhibited an inhibitory effect on the AngII­mediated suppression of CSE expression and activity in HUVECs. The effects of AngII were abrogated by sodium hydrosulfide (NaHS, an H2S donor), BQ788 or pyrrolidinedithiocarbamic acid (PDTC, an inhibitor of NF­κB). Furthermore, pretreatment with NaHS or PDTC attenuated AngII­induced apoptosis and cleaved caspase-12 generation. The pretreatment of HUVECs with BQ788 prior to AngII exposure mimicked the inhibitory effect of NaHS on the expression of p­p65 induced by AngII. In conclusion, the present study provides evidence that exogenous H-2S attenuates AngII­induced inflammation and cytotoxicity via inhibition of the ET­1/NF­κB signaling pathway in HUVECs.

[Regulation framework of watershed landscape pattern for non-point source pollution control based on 'source-sink' theory: A case study in the watershed of Maluan Bay, Xiamen City, China]. / 基于"源-汇"ç†è®ºçš„æµåŸŸéžç‚¹æºæ±¡æŸ“æŽ§åˆ¶æ™¯è§‚æ ¼å±€è°ƒæŽ§æ¡†æž¶­­ä»¥åŽ¦é—¨å¸‚马銮湾流域为例.

Watershed landscape pattern regulation and optimization based on 'source-sink' theory for non-point source pollution control is a cost-effective measure and still in the exploratory stage. Taking whole watershed as the research object, on the basis of landscape ecology, related theories and existing research results, a regulation framework of watershed landscape pattern for non-point source pollution control was developed at two levels based on 'source-sink' theory in this study: 1) at watershed level: reasonable basic combination and spatial pattern of 'source-sink' landscape was analyzed, and then holistic regulation and optimization method of landscape pattern was constructed; 2) at landscape patch level: key 'source' landscape was taken as the focus of regulation and optimization. Firstly, four identification criteria of key 'source' landscape including landscape pollutant loading per unit area, landscape slope, long and narrow transfer 'source' landscape, pollutant loading per unit length of 'source' landscape along the riverbank were developed. Secondly, nine types of regulation and optimization methods for different key 'source' landscape in rural and urban areas were established, according to three regulation and optimization rules including 'sink' landscape inlay, banding 'sink' landscape supplement, pollutants capacity of original 'sink' landscape enhancement. Finally, the regulation framework was applied for the watershed of Maluan Bay in Xiamen City. Holistic regulation and optimization mode of watershed landscape pattern of Maluan Bay and key 'source' landscape regulation and optimization measures for the three zones were made, based on GIS technology, remote sensing images and DEM model.

Gene transfection mediated by polyethyleneimine-polyethylene glycol nanocarrier prevents cisplatin-induced spiral ganglion cell damage.

Polyethyleneimine-polyethylene glycol (PEI-PEG), a novel nanocarrier, has been used for transfection and gene therapy in a variety of cells. In our previous study, we successfully carried out PEI-PEG-mediated gene transfer in spiral ganglion cells. It remains unclear whether PEI-PEG could be used for gene therapy with X-linked inhibitor of apoptosis protein (XIAP) in the inner ear. In the present study, we performed PEI-PEG-mediated XIAP gene transfection in the cochlea of Sprague-Dawley rats, via scala tympani fenestration, before daily cisplatin injections. Auditory brainstem reflex tests demonstrated the protective effects of XIAP gene therapy on auditory function. Immunohistochemical staining revealed XIAP protein expression in the cytoplasm of cells in the spiral ganglion, the organ of Corti and the stria vascularis. Reverse transcription-PCR detected high levels of XIAP mRNA expression in the cochlea. The present findings suggest that PEI-PEG nanocarrier-mediated XIAP gene transfection results in XIAP expression in the cochlea, prevents damage to cochlear spiral ganglion cells, and protects hearing.

Neuroendocrine mechanisms of left ventricular dysfunction stimulated by anger stress in rats with atherosclerosis--a putative role of natriuretic peptide.

OBJECTIVE: To investigate the role of natriuretic peptide in the process of left ventricular dysfunction caused by emotional stress. METHODS: Adult male SD rats (n=30) and Wistar rats (n=60) were selected in this study. Atherosclerosis models were induced with high-fat diet and excess VD3 injection (eight consecutive weeks), and anger stress models were prepared by resident-intruder stress experiment (two consecutive weeks). Furthermore, left ventricular functions were examined by high-resolution echocardiograph, after which left ventricular myocardium and coronary arteries were prepared for pathological section and observed with electron microscope. At the same time, the hypothalamus, medulla oblongata and left ventricular myocardium were also prepared for pathological sections to detect the localization and expression of ANP, BNP and NPR-A with immunofluorescence and western blot. RESULTS: We found that left ventricular functions of atherosclerosis or emotional stress modeled rats were both inferior to the healthy ones and superior to the combined (atherosclerosis and emotional stress) modeled ones (P<0.05). We also found that atherosclerosis and emotional stress could both cause morphological changes of left ventricular cells and capillary which contribute to apoptosis and hyperblastosis. Further more, there was NPR-A distributed in hypothalamus, medulla oblongata, as well as left ventricular tissues with the same express trend between groups, with atherosclerosis modeled rats the highest and the healthy rats the lowest. CONCLUSIONS: The results of our study suggest that anger stress could cause an excess consumption of ANP, BNP and NPR-A in nervous and cardiovascular system which inhibit the compensatory self-repair function of atherosclerosis rats, leading to a promotion of fibrosis and lipid peroxidation, offering insight into the neuroendocrine mechanisms of left heart function obstacle.

Overexpression of MicroRNA-1 improves the efficacy of mesenchymal stem cell transplantation after myocardial infarction.

BACKGROUND: The aim of this research was to study whether transplantation of mesenchymal stem cells (MSCs) overexpressing microRNA-1 into mouse infarcted myocardium can enhance cardiac myocyte differentiation and improve cardiac function efficiently. METHODS: Eight-week-old female C57BL/6 mice underwent ligation of the left coronary artery to produce models of myocardial infarction. The ligated animals were randomly divided into 4 groups (20 in each). One week later, they were intramyocardially injected at the heart infarcted zone with microRNA-1-transduced MSCs (MSC(miR-1) group), mock-vector-transduced MSCs (MSC(null) group), MSCs (MSC group) or medium (PBS group). At 4 weeks post-transplantation, transthoracic echocardiographic assessment, histological evaluation and Western blot were performed. RESULTS: The transplanted MSCs were able to differentiate into cardiomyocytes in the infarcted zone. Cardiac function in the MSC, MSC(null) and MSC(miR-1) groups was significantly improved compared to the PBS group (p < 0.01 or p < 0.001). However, treatment of MSCs expressing microRNA-1 was more effective for cardiac repair and improved cardiac function more efficiently by enhancing cell survival and cardiac myocyte differentiation compared to the MSC group or the MSC(null) groups (p < 0.05 or p < 0.01, respectively). CONCLUSIONS: Transplantation of microRNA-1-transfected MSCs was more conducive to repair of infarct injury and improved heart function by enhancing transplanted cells survival and cardiomyogenic differentiation.

[Changes of AFP and beta-hCG in testicular tumors analyzed by a function method].

OBJECTIVE: To establish a new function method for the analysis of a-fetoprotein (AFP) and beta-hCG in testicular tumors. METHODS: We reexamined the serum levels of AFP and beta-hCG after radical orchiectomy, and calculated the measured coordinate, with the abscissa representing the number of the half-lives of tumor markers, and the ordinate representing the measured value of tumor markers. Referring to the measured value of tumor markers before surgery as a, the number of half-lives as x, and their theoretical value over a period of x elimination half-lives as y (logarithm to the base 2 of y), we calculated the predicted coordinate according to the formula y = log2(a/2x) ==> x + y = log2a (function 1). Then we assessed tumor residue and metastasis by analyzing the relationship between the measured and predicted coordinates. RESULTS: The pathological examination of case 1 revealed a germ cell tumor of a mixed histological pattern of syncytiotrophoblast and yolk sac tumor. The measured coordinates of AFP and beta-hCG were (2.22, 6.21) and (10, 8.38), and the predicted coordinates (2.22, 6.34) and (10, 4.41) , indicating the elimination of the yolk sac tumor and metastasis of the syncytiotrophoblast tumor. Case 2 demonstrated the mixed pathological nature of teratocarcinoma and yolk sac tumor. The measured coordinates of AFP and beta-hCG were (2.67, -1.03) and (12, -3.32), and the predicted coordinates (2.67, 1.41) and (12, -5.80). But the review times of AFP and beta-hCG were out of the effective range of half-lives, with the measured values below the normal, which suggested no tumor residue or metastasis. Case 3 was found to be embryonal carcinoma. The measured coordinate of AFP was (0.22, 9.25) , and the predicted coordinate (0.22, 9.55) , indicating the elimination of tumor. CONCLUSION: The change of the tumor markers predicted by the function method coincided with the natural course of disease in the three cases. The coincidence of the measured with the predicted coordinate after radical orchiectomy indicates no metastasis, while their disagreement suggests possible residue and metastasis of the tumor.