Efficient optimization of an accelerator neutron source for neutron capture therapy using genetic algorithms.

BACKGROUND: In recent years, genetic algorithms have been applied in the field of nuclear technology design, producing superior optimization results compared to traditional methods. They can be employed in the design and optimization of beam shaping assemblies (BSA) BSA to obtain the desired neutron beams. But it should be noted that the direct combination of Monte Carlo methods with genetic algorithms requires a significant amount of computational resources and time. PURPOSE: Design and optimize BSA more efficiently to achieve neutron beams that meet specified recommendations. METHODS: We propose an approach of NSGA II with crucial variables which are identified by multivariate statistical techniques. This approach significantly reduces the problem sizes, thus reducing the time required for optimization. We illustrate this methodology using the example of BSA design for AB-BNCT. RESULTS: The computational efficiency has tripled with crucial variables. By using NSGA II, we obtained optimized models conforming to both the new and old version IAEA BNCT guidelines through a single optimization process and subjected them to phantom analysis. The results demonstrate that models obtained through this method can meet the IAEA recommendations with deep advantage depth (AD) and high absorbed ratio (AR). CONCLUSION: The genetic algorithm with crucial variables displays tremendous potential in addressing BSA optimization challenges.

Twice-daily rivaroxaban after percutaneous left atrial appendage closure for atrial fibrillation.

Background and aim: Rivaroxaban is an emerging oral anticoagulant for postoperative anticoagulation after percutaneous left atrial appendage closure (LAAC). Because a once-daily dosing regimen of rivaroxaban causes fluctuations in the drug plasma concentration, we studied the feasibility and safety of twice-daily rivaroxaban as a postoperative anticoagulation regimen for patients with atrial fibrillation (AF) undergoing LAAC. Methods: This study involved patients with AF who underwent LAAC and took rivaroxaban postoperatively. A total of 326 patients who received a standard total dose (15 or 20 mg) of rivaroxaban based on their creatinine clearance rate were divided into the twice-daily (BID) rivaroxaban group (n = 208) and once-daily (QD) rivaroxaban group (n = 118) according to their anticoagulation strategy. Transesophageal echocardiography was recommended at 3-6 months postoperatively to check for device-related thrombosis (DRT). Clinical outcomes were evaluated during postoperative anticoagulation. Results: The median CHA2DS2-VASc score (4 [3, 5] vs. 4 [3, 5], p = 0.28) and HAS-BLED score (2 [2, 3] vs. 2 [2, 3], p = 0.48) were not significantly different between the groups. During the anticoagulation period (4.1 ± 0.7 vs. 4.1 ± 0.9 months, p = 0.58), 148 (71.2%) patients in the BID group and 75 (63.6%) in the QD group underwent follow-up transesophageal echocardiography. There were no statistically significant differences between the two groups in terms of DRT (1.4% vs. 2.7%, p = 0.60), minor bleeding (8.2% vs. 11.0%, p = 0.39), thromboembolic events (1.0% vs. 0.8%, p = 1.00), major bleeding (0.5% vs. 0.8%, p = 1.00), or death. Conclusion: A short course of twice-daily rivaroxaban following LAAC is a feasible alternative regimen with a low rate of major bleeding events, DRT, and thromboembolic events for patients with AF.

Comparing safety and efficacy: MemoLefort versus watchman for left atrial appendage closure.

BACKGROUND: The MemoLefort is a new plug occluder for left atrial appendage closure (LAAC) in patients with atrial fibrillation (AF). This study compares the safety and efficacy of MemoLefort and the well-established Watchman occluder for LAAC. METHODS: Between January 2021 and September 2022, a cohort of 189 consecutive patients who underwent LAAC with MemoLefort or Watchman at The Second Affiliated Hospital of Wenzhou Medical University were included. Patients with MemoLefort or Watchman devices were compared in terms of the primary safety endpoints encompassing major periprocedural complications and major bleeding events at follow-up, the primary efficacy endpoint of all-cause stroke, systemic embolism and cardiovascular/unexplained death, and the combined hazard endpoint, a composite of all the above-mentioned hazards. RESULTS: Of the MemoLefort group (n = 83) and Watchman group (n = 106), the mean age, CHA2DS2-VASc score, and HAS-BLED score were 67.6 ± 9.2 vs. 69.0 ± 10.6 years, 3.9 ± 1.9 vs. 3.8 ± 1.9, and 1.6 ± 1.0 vs. 1.7 ± 1.2, respectively. After a median follow-up duration of 198 (99-329) vs. 334 (171-497) days, the primary endpoints of efficacy [2/49, 4.1% (MemoLefort) vs. 2/97, 2.1% (Watchman); hazard ratio (HR), 1.50; 95% confidence interval (CI), 0.20-11.08; P = 0.68] and safety (1/49, 2.0% vs. 5/97, 5.2%; HR, 0.26; 95% CI, 0.05-1.31; P = 0.19), as well as the combined hazard endpoint (3/49, 61% vs. 6/97, 6.2%; HR, 0.70; 95% CI, 0.18-2.58; P = 0.59) were similar between groups. CONCLUSIONS: In the short term, LAAC with MemoLefort provided similar efficacy, safety, and net clinical benefit in comparison to Watchman devices.

CTRP13 alleviates palmitic acid-induced inflammation, oxidative stress, apoptosis and endothelial cell dysfunction in HUVECs.

C1q/tumor necrosis factor-related protein 13 (CTRP13) has been reported to participate in cardiovascular diseases. However, the role and molecular mechanism of CTRP13 in obesity-induced endothelial cell damage is still unclear. In palmitic acid (PA)-induced human umbilical vein endothelial cells (HUVECs), qRT-PCR and western blot were used to examine CTRP13 expression. CCK-8 and TUNEL assays were adopted to assess cell viability and apoptosis, respectively. ROS level and MDA content were evaluated by their commercial kits and inflammatory cytokines were measured using ELISA. Endothelial cell dysfunction was evaluated by detecting NO production and eNOS expression, and tube formation assay was performed to assess angiogenesis. AMPK pathway-related proteins were detected by western blot. The results showed that CTRP13 was downregulated in PA-induced HUVECs. CTRP13 overexpression reduced PA-induced cell viability loss and oxidative stress in HUVECs. Moreover, CTRP13 overexpression suppressed PA-induced inflammation and apoptosis, improved angiogenesis ability, and alleviated endothelial cell dysfunction in HUVECs. In addition, CTRP13 overexpression activated AMPK pathway and regulated the expressions of downstream NOX1/p38 and KLF2. Furthermore, compound C countervailed the impacts of CTRP13 overexpression on cell viability, oxidative stress, inflammation, apoptosis and endothelial function in PA-induced HUVECs. To sum up, CTRP13 overexpression may alleviate PA-induced endothelial cell damage.

A Molecular Integrative Study on the Inhibitory Effects of WRR and ERW on Amyloid ß Peptide (1-42) Polymerization and Cell Toxicity.

Alzheimer's disease (AD) is a neurodegenerative disease and the main pathological characteristic of AD is the deposition of Aß42 in the brain. Inhibition of Aß42 polymerization is one of the important research directions. Due to the pathological complexity of Alzheimer's disease, studies on Aß42 polymerization inhibitors have not made significant progress worldwide. Using an independently constructed structure database of oligopeptides, in this study, molecular docking, umbrella sampling analysis of free energy, ThT fluorescence detection of Aß42 polymerization, transmission electron microscopy, and flow cytometry detection of reactive oxygen species (ROS) and apoptosis were performed to screen tripeptides and pentapeptides that inhibit polymerization. It was found that two tripeptides, i.e., WRR and ERW, bind stably to the core of Aß42 polymerization in the molecular dynamics analysis, and they significantly inhibited the aggregation of Aß42 and reduced their cell toxicity in vitro.

Correction: Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities.

[This corrects the article DOI: 10.3762/bjoc.19.59.].

Secondhand smoke exposure and ocular health: A systematic review.

The toxicology of secondhand smoke (SHS), along with the harm of its exposure to human health, has been generally acknowledged; however, specific evidence is lacking on the association between SHS exposure and ocular health. In this systematic review (PROSPERO registration number: CRD42022247992), we included 55 original articles published by 12 May 2023, which dealt with SHS exposure and ocular disorders, such as eye irritation, conjunctivitis, dry eye diseases, uveitis, myopia, astigmatism, contact lens discomfort, age-related macular degeneration, glaucoma, and thyroid eye disease that addressed the ocular neurovascular structures of the macular, retinal nerve fiber layer, choroid, and corneal biomechanical parameters. We found compelling correlational evidence for eye irritation, conjunctivitis, and dry eye symptoms-supporting that SHS exposure was positively associated with inflammatory and allergic changes in the eyes. Yet, evidence about the associations between SHS exposure and other ocular disorders, structures, and parameters is still limited or controversial. Given the limitations of existing literature, more investigations with high quality and rigorous design are warranted to elucidate the potentially harmful effects of SHS exposure on ocular health.

A multibiomarker approach to assess the ecotoxicological effects of diclofenac on Asian clam Corbicula fluminea (O. F. Müller, 1774).

Diclofenac (DCF), one of the most current and widely used nonsteroidal anti-inflammatory drugs (NSAIDs), has been frequently detected in aquatic environments worldwide. However, the ecotoxicological effects of DCF on freshwater invertebrates remain largely unknown. In the present study, Corbicula fluminea were exposed to environmentally relevant concentrations of DCF (0, 2, 20, and 200 µg/L) for 28 days, and the potential adverse effects of DCF on siphoning behavior, antioxidant responses, and apoptosis were investigated. Our results showed that the siphon efficiencies of clams were significantly suppressed under DCF stress. DCF exerted neurotoxicity via reducing the activity of acetylcholinesterase (AChE) in gills and digestive gland of C. fluminea. Exposure to DCF induced antioxidant stress and increased malondialdehyde (MDA) levels in both gills and digestive gland of C. fluminea. Transcriptional alterations of apoptosis-related genes indicated that DCF might induce apoptosis by triggering mitochondrial apoptotic pathway. These findings can improve our understanding of the ecological risk of DCF in freshwater ecosystems.

Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities.

Six new compounds, including a tetralone 1, two xanthones 2 and 3, a flavan derivative 4, and two nor-diterpenoids 7 and 8, accompanied by two known flavan derivatives 5 and 6 and a known olefine acid (9) were isolated from whole bodies of Kronopolites svenhedini (Verhoeff). The structures of the new compounds were determined by 1D and 2D nuclear magnetic resonance (NMR) and other spectroscopic methods, as well as computational methods. Selected compounds were evaluated for their biological properties against a mouse pancreatic cancer cell line and inhibitory effects on iNOS and COX-2 in RAW264.7 cells.

qTPI: A quasi-toxicity probability interval design for phase I trials with multiple-grade toxicities.

The common terminology criteria for adverse events by the National Cancer Institute has greatly facilitated the revolution of drug development and an increasing number of Phase I trials have started to collect multiple-grade toxicity endpoints. Appropriate and yet transparent Phase I statistical designs for multiple-grade toxicities are therefore in great needs. In this article, we propose a quasi-toxicity probability interval (qTPI) design that incorporates a quasi-continuous measure of the toxicity probability (qTP) into the Bayesian theoretic framework of the interval based designs. Multiple-grade toxicity outcomes of each patient are mapped to qTP according to a severity weight matrix. Dose-toxicity curve underlying the dosing decisions in the qTPI design is continuously updated using accumulating trial data. Numerical simulations investigating the operating characteristics of qTPI show that qTPI achieved better safety, accuracy and reliability compared to designs that rely on binary toxicity data. Furthermore, parameter elicitation in qTPI is simple and does not involve multiple hypothetical cohorts specification. Finally, a hypothetical soft tissue sarcoma trial with six toxicity types and grade 0 to grade 4 severity grades is illustrated with patient-by-patient dose allocation under the qTPI design.

Sputtered anti-reflection layer on transparent polyimide - substrate improves adhesion strength to - copper layer: effects of layer thickness and sputtering power.

In order to shield the electronic circuits on a transparent polyimide (PI) substrate, an anti-reflection (AR) layer was deposited on a PI film via DC reactive magnetron sputtering. The effects of sputtering power and thickness of AR layer on the optical property and adhesion strength of the PI were investigated. The composition of the AR layer influences the bonding between layers. Sufficient thickness of the AR layer is essential to strengthen the adhesion between the PI and copper (Cu) layers. The sputtered AR layer on the PI also improves the barrier property for water vapor. The AR layer-sputtered PI substrates remain transparent and exhibit high peel strength to the Cu layer, suggesting their potential applications as reliable transparent substrates for modern electronic devices.

Analysis of Secondhand Smoke Exposure and Myopia Among Children Aged 6 to 8 Years in Hong Kong.

Importance: Secondhand smoke (SHS) exposure potentially threatens ocular health; however, its association with myopia is unknown. Objective: To examine the association between SHS exposure and childhood myopia. Design, Setting, and Participants: Cross-sectional data from the population-based Hong Kong Children Eye Study were used. Data were collected from March 5, 2015, to September 12, 2021, at The Chinese University of Hong Kong Eye Center. Participants included children aged 6 to 8 years. Secondhand smoke exposure was evaluated using a validated questionnaire. All participants underwent comprehensive ophthalmic and physical examinations. Exposure: Secondhand smoke exposure. Main Outcomes and Measures: Generalized estimating equations were constructed to examine the association of SHS exposure with spherical equivalent and axial length; logistic regression models, with myopia rate; and linear regression models, with myopia onset. Results: A total of 12 630 children (mean [SD] age, 7.37 [0.88] years; 53.2% boys) were included in the analysis. Among the participants, 4092 (32.4%) had SHS exposure. After adjusting for age, sex, parental myopia, body mass index, near-work time, outdoor time, and family income, SHS exposure was associated with greater myopic refraction (ß = -0.09 [95% CI, -0.14 to -0.03]) and longer axial length (ß = 0.05 [95% CI, 0.02-0.08]). Children with SHS exposure were more likely to develop moderate (odds ratio [OR], 1.30 [95% CI, 1.06-1.59]) and high myopia (OR, 2.64 [95% CI, 1.48-4.69]). The association of SHS exposure with spherical equivalence and axial length was magnified in younger children. For each younger year of a child's exposure to SHS, SHS exposure was associated with a 0.07-D decrease in spherical equivalence (ß = 0.07 [95% CI, 0.01-0.13]) and a 0.05-mm increase in axial length (ß = -0.05 [95% CI, -0.08 to -0.01]). Exposure to SHS was associated with an earlier mean (SD) age at onset of myopia (72.8 [0.9] vs 74.6 [0.6] months; P = .01). Every increase in SHS exposure in units of 10 cigarettes per day was associated with greater myopic refraction (ß = -0.07 [95% CI, -0.11 to -0.02]), axial length (ß = 0.04 [95% CI, 0.01-0.06]), and likelihood of developing moderate (OR, 1.23 [95% CI, 1.05-1.44]) and high myopia (OR, 1.75 [95% CI, 1.20-2.56]), and earlier myopia onset (ß = -1.30 [95% CI, -2.32 to -0.27]). Conclusions and Relevance: The findings of this cross-sectional study suggest that SHS exposure was associated with greater myopic refraction, longer axial length, greater likelihood of developing moderate and high myopia, and earlier myopia onset. The larger the quantity of SHS exposure and the younger the child, the more advanced myopia development and progression with which SHS exposure is associated.

Molecular Integrative Analysis of the Inhibitory Effects of Dipeptides on Amyloid ß Peptide 1-42 Polymerization.

The major pathological feature of Alzheimer's disease (AD) is the aggregation of amyloid ß peptide (Aß) in the brain. Inhibition of Aß42 aggregation may prevent the advancement of AD. This study employed molecular dynamics, molecular docking, electron microscopy, circular dichroism, staining of aggregated Aß with ThT, cell viability, and flow cytometry for the detection of reactive oxygen species (ROS) and apoptosis. Aß42 polymerizes into fibrils due to hydrophobic interactions to minimize free energy, adopting a ß-strand structure and forming three hydrophobic areas. Eight dipeptides were screened by molecular docking from a structural database of 20 L-α-amino acids, and the docking was validated by molecular dynamics (MD) analysis of binding stability and interaction potential energy. Among the dipeptides, arginine dipeptide (RR) inhibited Aß42 aggregation the most. The ThT assay and EM revealed that RR reduced Aß42 aggregation, whereas the circular dichroism spectroscopy analysis showed a 62.8% decrease in ß-sheet conformation and a 39.3% increase in random coiling of Aß42 in the presence of RR. RR also significantly reduced the toxicity of Aß42 secreted by SH-SY5Y cells, including cell death, ROS production, and apoptosis. The formation of three hydrophobic regions and polymerization of Aß42 reduced the Gibbs free energy, and RR was the most effective dipeptide at interfering with polymerization.

Isolation and Characterization of trans-p-Hydroxycinnamoyl Meroterpenoids from Ganoderma sinensis.

Zizhines V, W, Y, Z, (±)-zizhines X, and Z1-Z3, and (±)-ganosinensol L, thirteen new compounds including four pairs of enantiomers and a known compound (-)-ganosinensol L, were isolated from the fruiting bodies of Ganoderma sinensis. Their structures were identified by spectroscopic, computational methods, and CD (circular dichroism spectroscopy) comparisons. Zizhines V-Z and Z1-Z3 are meroterpenoids consisting of the phenolic and the terpenoidal parts. All the compounds except zizhine Z3 bear a common trans-p-hydroxycinnamoyl group. Biological evaluation shows that (-)-zizhine Z1 inhibits cell migration in the MDA-MB-231 cell lines. The present study discloses the chemical profiling of G. sinensis and paves the way for its development as functional products to benefit chronic disorders.

Anti-reflection Layer-Sputtered Transparent Polyimide Substrate with Reliable Adhesion Strength to the Copper Layer.

Parameters of DC-reactive magnetron sputtering are optimized to deposit anti-reflection (AR) layers on transparent polyimide (PI) substrates, followed by the deposition of the conductive copper layer, to fabricate practically reliable composite films as advanced flexible circuits. When the deposition thickness is controlled and the gas composition during sputtering is adjusted, the resultant AR layer-coated PI film exhibits low reflectance and reveals improved adhesion strength to the copper layer. The adhesion reliability tests confirm that the peel strength between the PI film and the deposited layers could be further improved after thermal processing due to the formation of a worm-like morphology for better mechanical interlocking with layers. The facile sputtering process successfully fabricates a reliable substrate material with low reflectance and sufficient adhesion strength to copper for application as flexible printed circuits.

Association of SIX1-SIX6 polymorphisms with peripapillary retinal nerve fibre layer thickness in children.

PURPOSE: Association of SIX1-SIX6 variants with peripapillary retinal nerve fibre layer (p-RNFL) thickness had been reported in adults. This study aimed to investigate these associations in children, with further explorations by spatial, age and sex stratifications. METHODS: 2878 school children aged between 6 and 9 years were enrolled from the Hong Kong Children Eye Study. Three single-nucleotide polymorphisms (SNPs) at the SIX1-SIX6 locus were genotyped. The association of each SNP with p-RNFL thickness (including global and sectoral thickness) were evaluated using multiple linear regression. RESULTS: SNPs rs33912345 (p=7.7×10-4) and rs10483727 (p=0.0013) showed significant associations with temporal-inferior p-RNFL thickness. The C allele of rs33912345 was associated with a thinner temporal-inferior p-RNFL by an average of 2.44 µm, while rs10483727-T was associated with a thinner temporal-inferior p-RNFL by 2.32 µm. The association with temporal-inferior p-RNFL was the strongest in the 8-9 year-old group for rs33912345 (p=5.2×10-4) and rs10483727 (p=3.3×10-4). Both SNPs were significantly associated with temporal-inferior p-RNFL thickness in boys (p<0.0017), but not in girls (p>0.05). In contrast, rs12436579-C (ß=1.66; p=0.0059), but not rs33912345-C (ß=1.31; p=0.052) or rs10483727-T (ß=1.19; p=0.078), was nominally associated with a thicker nasal-inferior p-RNFL. CONCLUSIONS: Both rs33912345 and rs10483727 at SIX1-SIX6 were associated with p-RNFL thickness in children, especially at the temporal-inferior sector, with age-dependent and sex-specific effects. SNP rs12436579 was associated with nasal-inferior p-RNFL thickness. Our findings suggested a role of SIX1-SIX6 in RNFL variation during neural retina development in childhood.

The protective effect of LCZ696 in coxsackievirus B3-induced acute viral myocarditis mice.

AIMS: Acute viral myocarditis (AVMC) is the aetiology of heart failure (HF) with few specific treatments. The improvement of left ventricular ejection fraction (LVEF) is a critical predictor for the prognosis of AVMC. LCZ696 is a drug used in HF to improve LVEF, with a few research on AVMC. In this research, we evaluated the effects and mechanism of LCZ696 in improving LVEF in AVMC. METHODS: Eighty 4-week-old male BALB/c mice were randomly divided into four groups of 20: Sham; Sham + LCZ696 (60 mg/kg/d); AVMC; AVMC + LCZ696. The above experiments were repeated by CVB3-infected HL-1 and Mdivi-1 to down-regulated dynamin-related protein 1(Drp1). Adeno-associated virus 9 (AAV9) with enhanced green fluorescent proteins (GFP) was injected to produce Drp1-overexpression mice and set up four groups: AVMC group, AVMC + AAV group, AVMC + LCZ696 group, and AVMC + LCZ696 + AAV group (n = 20 in each group). LVEF was evaluated by echocardiography at a similar heart rate (HR) at d7, Drp1 (p-Drp1), inflammation and apoptosis by histology and Western blot (WB), and mitochondrial by electron microscopy. RESULTS: Cardiac function were injured in AVMC that LCZ696 reversed (LVEF, %: Sham: 68.99 ± 9.67; Sham + LCZ696: 71.96 ± 6.20; AVMC: 30.95 ± 6.40*; AVMC + LCZ696: 68.99 ± 9.67*#, *P < 0.05 vs. Sham, #P < 0.05 vs. AVMC). LCZ696 attenuated p-Drp1 expression, inflammation, apoptosis, and mitochondrial fission (p-Drp1/Drp1: Sham: 1; Sham + LCZ696: 1.37 ± 0.22; AVMC: 2.29 ± 0.36*; AVMC+LCZ696: 1.43 ± 0.08*#, *P < 0.05 vs. Sham, #P < 0.05 vs. AVMC). Some of the above results were repeated in CVB3-infected HL-1 cells and Mdivi-1. AAV increased Drp1 expression and mitochondrial fission, inflammatory, and apoptosis. Compared with the AVMC + AAV group, the LVEF increased from 24.44 ± 0.03% to 32.33 ± 0.05% in the AVMC + LCZ696 + AAV group(P < 0.05), p-Drp1/Drp1 decreased from 0.54 ± 0.12 to 0.42 ± 0.09*, and IL-6, c-IL-1ß, and c-caspase-3/caspase-3 decreased from 1.07 ± 0.22 to 0.72 ± 0.08*, from 1.03 ± 0.14 to 0.79 ± 0.09*, and from 4.69 ± 0.29 to 0.92 ± 0.13*, respectively (*P < 0.05). CONCLUSIONS: LCZ696 has a protective effect on AVMC by improving LVEF and reducing inflammation and apoptosis, which may be due to the inhibition of Drp1-mediated mitochondrial fission.

Percutaneous left atrial appendage closure using the LAmbre device in patients with atrial fibrillation and left atrial appendage thrombus.

Background: Left atrial appendage closure (LAAC) is considered a valid alternative for the prevention of thromboembolic stroke in patients with persistent left atrial appendage thrombus (LAAT) despite adequate anticoagulation. However, the data on LAAC using the LAmbre device for patients with LAAT is limited. This study was performed to explore efficacy and safety as well as to share the experience of the modified LAAC procedure with the LAmbre device. Materials and methods: A total of 7 patients with persistent LAAT despite adequate anticoagulation underwent modified LAAC with the LAmbre device between November 2019 and April 2022. Transesophageal echocardiography was performed 3 months postoperatively to detect device-related thrombosis and peridevice leak. The patients' clinical events were evaluated during the perioperative and follow-up periods. Results: The median age, CHA2DS2-VASc score, and HAS-BLED score of all patients were 71 [53-73], 3 [2-4], and 2 [2-3], respectively. In the procedure, a cerebral protection system was used in two patients. LAAC with the LAmbre device was successfully performed in all patients without perioperative events. During the median follow-up of 383 [325-865] days, postoperative transesophageal echocardiography was performed in six (85.7%) patients. Device-related thrombosis was detected in one (16.7%) patient, and no significant peridevice leak was observed. No thromboembolic event or bleeding event occurred in any patients. Conclusion: LAAC with the LAmbre device is effective and safe when performed by experienced operators in highly selected patients with LAAT after adequate anticoagulation.

Combined atrial fibrillation ablation and left atrial appendage closure: Watchman vs. LAmbre devices.

Background: Left atrial appendage closure (LAAC) combined with radiofrequency catheter ablation is an emerging one-stop hybrid procedure for non-valvular atrial fibrillation (AF). This study was performed to compare the efficacy and safety of the Watchman device vs. the LAmbre device for this combined procedure. Methods: Two hundred and thirty two patients with AF who underwent the combined procedure were enrolled and divided into two subgroups depending on the device choice: the Watchman-combined group (n = 118) and the LAmbre-combined group (n = 114). The periprocedural and follow-up adverse events in both groups were documented. Results: The mean CHA2DS2-VASc score and HAS-BLED score in the Watchman-combined group and LAmbre-combined group were 3.7 ± 1.5 vs. 3.8 ± 1.5 and 2.5 ± 1.1 vs. 2.3 ± 1.1, respectively (all P > 0.05). Successful LAAC was achieved in all patients. The rate of major periprocedural complications and AF recurrence at 6 months post-procedure were similar between the Watchman-combined group and LAmbre-combined group (0.8 vs. 0.9%, P = 1.00; 22.0 vs. 15.8%, P = 0.23). During 2.6 ±0 .7 vs.1.6 ± 1.6 years follow-up, the rate of major clinical adverse events, including stroke and major bleeding, were comparable between the Watchman-combined group and the LAmbre-combined group (2.6 vs. 1.1% per 100 patient-years, P = 0.33). The intraprocedural peri-device leakage (PDL) rate was similar between the Watchman-combined group and the LAmbre-combined group (5.1 vs. 6.1%, P = 0.73), but the PDL rate was significantly higher at 3-6 months transesophageal echocardiography (TEE) follow-up than the intraprocedural PDL rate in both groups (21.6 vs. 5.1%; 36.6 vs. 6.1%, respectively), with a more obvious increase in minimal PDL rate in the LAmbre-combined group than the Watchman-combined group (36.6 vs. 21.6%, P < 0.05). Conclusion: The Watchman and LAmbre devices were comparable in efficacy and safety for the combined procedure. The minimal PDL rate at short-term TEE follow-up was higher in the LAmbre-combined group than the Watchman-combined group.

Electroacupuncture Improves Intestinal Motility through Exosomal miR-34c-5p Targeting SCF/c-Kit Signaling Pathway in Slow Transit Constipation Model Rats.

Background: The pathogenesis of slow transit constipation (STC) is associated with exosomal miR-34c-5p. Electroacupuncture (EA) improves gastrointestinal motility in gastrointestinal disorders, especially STC. Our study aimed to explore the mechanism by which EA improves intestinal motility by modulating the release of exosomes and the transmission of exosomal miR-34c-5p. Methods: Fifty rats were randomly divided into five groups. STC model rats were induced, and GW4869, the exosome release inhibitor, was used to inhibit the release of exosome. The serum exosomes were authenticated under a transmission electron microscope and nanoparticle tracking analysis. RT-qPCR detected the expression of miR-34c-5p in serum exosomes and colonic tissues. The fecal number in 24 hours, Bristol scores, and intestinal transit rates were used to assess intestinal motility. Subsequently, hematoxylin and eosin (H&E) staining was used to examine the colonic mucosal histology. Finally, the expression of stem cell factor (SCF) and receptor tyrosine kinase (c-Kit) protein was measured using immunohistochemistry staining. Results: We found that EA upregulated exosomal miR-34c-5p in serum and downregulated miR-34c-5p in colonic tissues (P < 0.01). EA improved fecal numbers in 24 hours, Bristol scores, and intestinal transit rates in STC rats (P < 0.01). EA recovered the colonic histological structure and enhanced the expression of SCF and c-Kit protein (P < 0.01). The therapeutic effect of EA was attenuated after inhibiting the release of the exosome. Conclusion: Our results indicated that EA improves intestinal motility in STC rats by transporting of exosomal miR-34c-5p targeting the SCF/c-Kit signaling pathway.