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BackgroundThe electromechanical dyssynchrony associated with right ventricular pacing (RVP) has been found to have adverse impact on clinical outcomes. Several studies have shown that left bundle branch area pacing (LBBAP) has superior pacing parameters compared with RVP. We aimed to assess the difference in ventricular electromechanical synchrony and investigate the risk of atrial high-rate episodes (AHREs) in patients with LBBAP and RVP.MethodsWe consecutively identified 40 patients with atrioventricular block and no prior atrial fibrillation. They were divided according to the ventricular pacing sites: the LBBAP group and the RVP group (including the right ventricular apical pacing (RVA) group and the right side ventricular septal pacing (RVS) group). Evaluation of ventricular electromechanical synchrony was implemented using electrocardiogram and two-dimensional speckle tracking echocardiography (2D-STE). AHRE was defined as event with an atrial frequency of ≥176 bpm lasting for ≥6 min recorded by pacemakers during follow-up.ResultsThe paced QRS duration of the LBBAP group was significantly shorter than that of the other two groups: LBBAP 113.56 ± 9.66 ms vs. RVA 164.73 ± 14.49 ms, p

Background: Sirolimus is increasingly utilized in treating diseases associated with mTOR pathway overactivation. Despite its potential, the lack of evidence regarding its long-term safety across all age groups, particularly in pediatric patients, has limited its further application. This study aims to assess the long-term safety of sirolimus, with a specific focus on its impact on growth patterns in pediatric patients. Methods: This pooled analysis inlcudes two prospective cohort studies spanning 10 years, including 1,738 participants (aged 5 days to 69 years) diagnosed with tuberous sclerosis and/or lymphangioleiomyomatosis. All participants were mTOR inhibitor-naive and received 1 mg/m²/day of sirolimus, with dose adjustments during a two-week titration period to maintain trough blood concentrations between 5 and 10 ng/ml (maximum dose 2 mg). Indicators of physical growth, hematopoietic, liver, renal function, and blood lipid levels were all primary outcomes and were analyzed. The adverse events and related management were also recorded. Results: Sirolimus administration did not lead to deviations from normal growth ranges, but higher doses exhibited a positive association with Z-scores exceeding 2 SD in height, weight, and BMI. Transient elevations in red blood cell and white blood cell counts, along with hyperlipidemia, were primarily observed within the first year of treatment. Other measured parameters remained largely unchanged, displaying only weak correlations with drug use. Stomatitis is the most common adverse event (920/1738, 52.9%). In adult females, menstrual disorders were observed in 48.5% (112/217). Conclusions: Sirolimus's long-term administration is not associated with adverse effects on children's physical growth pattern, nor significant alterations in hematopoietic, liver, renal function, or lipid levels. A potential dose-dependent influence on growth merits further exploration. Trial registration: Pediatric patients: Chinese clinical trial registry, No. ChiCTR-OOB-15,006,535. Adult patients: ClinicalTrials, No. NCT03193892. [ABSTRACT FROM AUTHOR]

Background: Addison's disease and X-linked adrenoleukodystrophy (X-ALD) (Addison's-only) are two diseases that need to be identified. Addison's disease is easy to diagnose clinically when only skin and mucosal pigmentation symptoms are present. However, X-ALD (Addison's-only) caused by ABCD1 gene variation is ignored, thus losing the opportunity for early treatment. This study described two patients with initial clinical diagnosis of Addison's disease. However, they rapidly developed neurological symptoms triggered by infection. After further genetic testing, the two patients were diagnosed with X-ALD. Methods: We retrospectively analyzed X-ALD patients admitted to our hospital. Clinical features, laboratory test results, and imaging data were collected. Whole-exome sequencing was used in molecular genetics. Results: Two patients were included in this study. Both of them had significantly increased adrenocorticotropic hormone level and skin and mucosal pigmentation. They were initially clinically diagnosed with Addison's disease and received hydrocortisone treatment. However, both patients developed progressive neurological symptoms following infectious disease. Further brain magnetic resonance imaging was completed, and the results suggested demyelinating lesions. Molecular genetics suggested variations in the ABCD1 gene, which were c.109_110insGCCA (p.C39Pfs*156), c.1394–2 A > C (NM_000033), respectively. Therefore, the two patients were finally diagnosed with X-ALD, whose classification had progressed from X-ALD (Addison's-only) to childhood cerebral adrenoleukodystrophy (CCALD). Moreover, the infection exacerbates the demyelinating lesions and accelerates the onset of neurological symptoms. Neither the two variation sites in this study had been previously reported, which extends the ABCD1 variation spectrum. Conclusions: Patients with only symptoms of adrenal insufficiency cannot be simply clinically diagnosed with Addison's disease. Being alert to the possibility of ABCD1 variation is necessary, and complete genetic testing is needed as soon as possible to identify X-ALD (Addison's-only) early to achieve regular monitoring of the disease and receive treatment early. In addition, infection, as a hit factor, may aggravate demyelinating lesions of CCALD. Thus, patients should be protected from external environmental factors to delay the progression of cerebral adrenoleukodystrophy. [ABSTRACT FROM AUTHOR]

Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully established to determine the anti-obesity properties of t10c12-CLA in male mice that could produce endogenous t10c12-CLA. To test whether there is a different impact of t10c12-CLA on lipid metabolism in both sexes, this study investigated the adiposity and metabolic profiles of female Pai mice that exhibited a dose-dependent expression of foreign Pai gene and a shift of t10c12-CLA content in tested tissues. Compared to their gender-match wild-type littermates, Pai mice had no fat reduction but exhibited enhanced lipolysis and thermogenesis by phosphorylated hormone-sensitive lipase and up-regulating uncoupling proteins in brown adipose tissue. Simultaneously, Pai mice showed hepatic steatosis and hypertriglyceridemia by decreasing gene expression involved in lipid and glucose metabolism. Further investigations revealed that t10c10-CLA induced excessive prostaglandin E2, adrenaline, corticosterone, glucagon and inflammatory factors in a dose-dependent manner, resulting in less heat release and oxygen consumption in Pai mice. Moreover, fibroblast growth factor 21 overproduction only in monoallelic Pai/wt mice indicates that it was sensitive to low doses of t10c12-CLA. These results suggest that chronic t10c12-CLA has system-wide effects on female health via synergistic actions of various hormones. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the relationship between psychological resilience, thriving at work, and work performance among nurses, as well as analyse the mediating role of thriving at work in the relationship between psychological resilience and the work performance of nurses. The findings are intended to serve as a reference for nursing managers to design tailored work performance intervention programs. Method: Using convenience sampling, 308 clinical nurses were selected from a tertiary hospital in Changsha City, Hunan Province, China, from February to April 2023. The Connor–Davidson Resilience Scale (CD-RISC), the Thriving at Work Scale, and the Work Performance Scale were employed for the questionnaire survey. Pearson correlation analysis was used to explore the relationship between psychological resilience, thriving at work and work performance. The SPSS 26.0 software's 'Process' plugin was utilised for mediation effect analysis. Results: Significantly positive correlations were found between psychological resilience and thriving at work (r = 0.806, P < 0.01), thriving at work and work performance (r = 0.571, P < 0.01) as well as psychological resilience and work performance (r = 0.572, P < 0.01). Psychological resilience significantly predicted work performance positively (β = 0.558, t = 11.165, P < 0.01), and this prediction remained significant when thriving at work (the mediating variable), was introduced (β = 0.371, t = 4.772, P < 0.01). Psychological resilience significantly predicted thriving at work positively (β = 0.731, t = 20.779, P < 0.01), and thriving at work significantly predicted work performance positively (β = 0.256, t = 3.105, P < 0.05). The mediating effect size of thriving at work between psychological resilience and work performance was 33.49% (P < 0.05). Conclusion: Thriving at work plays a partial mediating role between psychological resilience and work performance. The level of work performance among clinical nurses was relatively high. Nursing managers can enhance thriving at work by fostering psychological resilience among clinical nurses, thereby further improving their work performance to ensure high-quality and efficient nursing care. [ABSTRACT FROM AUTHOR]

Background: Protein ubiquitination is a common post-translational modification involved in protein degradation and various life processes in cells. NEDL1 is a ubiquitin ligase that is highly expressed primarily in the brain. However, the functions of NEDL1 in social approach/novelty preference, anxiety, learning and memory remain poorly understood., Methods: Nedl1 knockout mice (Nedl1 -/- ) and wild-type mice (Nedl1 +/+ ) were tested using three-chamber test, elevated plus maze, and Barnes maze. Then, brain tissue was stained, and blood was collected for metabolic analysis., Results: Compared with Nedl1 +/+ mice, Nedl1 -/- mice showed no differences in social approach/novelty preference and anxiety behavior. Nedl1 -/- mice displayed impaired learning and memory. Nedl1 knockout did not affect the number of neurons and oligodendrocytes in the hippocampus. Astrocytes proliferated in the hippocampus of Nedl1 -/- mice. The amino acid metabolism of Nedl1 +/+ and Nedl1 -/- mice is different, especially the increase in proline and tryptophan., Conclusion: This study showed that Nedl1 knockout impaired learning and memory, which may be related to astrocyte proliferation and amino acid metabolism change. Nedl1 knockout did not affect social style/novelty preference and anxiety behavior in mice. The preliminary study of NEDL1 in neurobehavioral function could help understand the role of NEDL1 in the nervous system., Competing Interests: Declaration of competing interests The authors have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Postoperative ileus (POI) is a common complication after abdominal surgery with high morbidity, which hinders patient recovery, prolongs hospitalization, and increases healthcare costs. Therefore, POI has become a global public health challenge. POI triggering is multifactorial. Autonomic and hormonal mechanisms are generally involved in POI pathogenesis. Recent studies have shown that beta adrenergic signaling of enteric glia is a POI trigger. Currently, the status quo, trends, and frontiers of global research on POI remain unclear., Aim: To explore the current status, trends, and frontiers of POI research from 2011 to the present based on bibliometric analysis., Methods: Publications published on POI research from 2011 to 2023 were retrieved on June 1, 2023, from the Web of Science Core Collection. CiteSpace 6.2.R2 and VOSviewer were used to conduct bibliometric visualization., Results: In total, 778 POI records published from 2011 to 2023 were retrieved. Over the past few decades, the annual cumulative number of related articles has linearly increased, with China and the United States of America contributing prominently. All publications were from 59 countries and territories. China and the University of Bonn were the top contributing country and institution, respectively. Neurogastroenterology & Motility was the most prolific journal. The Journal of Gastrointestinal Surgery had the highest number of citations. Wehner Sven was the most productive author. Burst keywords ( e.g. , colon, prolonged ileus, acupuncture, paralytic ileus, pathophysiology, rectal cancer, gastrointestinal function, risk) and a series of reference citation bursts provided evidence for the research frontiers in recent years., Conclusion: This study demonstrates trends in the published literature on POI and provides new insights for researchers. It emphasizes the importance of multidisciplinary cooperation in the development of this field., Competing Interests: Conflict-of-interest statement: All authors have no conflicts of interest to report., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

To explore the stabilization effect of livestock manure biochar on Cd-contaminated soil and its impact on the soil environment, a pot experiment was conducted to investigate the stabilization efficiency of cattle manure-biochar （BC） and thiol-modified biochar （SBC） on Cd in soil and their effect on the soil properties and microbial community. The structural equation model （SEM） was used to analyze the effect pathways of BC and SBC on the soil microbial community. The results showed that BC and SBC increased soil pH, available potassium, available phosphorus, and organic matter content but decreased soil available nitrogen content compared with those in CK. The stabilization efficiency of BC for Cd in soil was 14.97%, which was much lower than that of SBC （85.71%）. Moreover, SBC increased the abundance of dominant bacterial phyla in soil, with Proteobacteria, Bacteroidota, and Cyanobacteria increasing most significantly. SBC decreased the diversity of soil microorganisms, but the decrease was insignificant （ P ≥0.05） compared with that in CK and BC. SEM analysis indicated that the available phosphorus, available potassium, organic matter, and soil pH were the key factors influencing Cd availability in soil, whereas organic matter and Cd availability were the key factors affecting the soil microbial community. Overall, SBC could stabilize Cd effectively and increase the abundance of dominant bacteria and has great potential in the remediation of Cd-contaminated soil.

Objectives: This study aimed to analyze active compounds and signaling pathways of CH applying network pharmacology methods, and to additionally verify the molecular mechanism of CH in treating AP., Materials and Methods: Network pharmacology and molecular docking were firstly used to identify the active components of CH and its potential targets in the treatment of AP. The pancreaticobiliary duct was retrogradely injected with sodium taurocholate (3.5%) to create an acute pancreatitis (AP) model in rats. Histological examination, enzyme-linked immunosorbent assay, Western blot and TUNEL staining were used to determine the pathway and mechanism of action of CH in AP., Results: Network pharmacological analysis identified 168 active compounds and 276 target proteins. In addition, there were 2060 targets associated with AP, and CH had 177 targets in common with AP. These shared targets, including STAT3, IL6, MYC, CDKN1A, AKT1, MAPK1, MAPK3, MAPK14, HSP90AA1, HIF1A, ESR1, TP53, FOS, and RELA, were recognized as core targets. Furthermore, we filtered out 5252 entries from the Gene Ontology(GO) and 186 signaling pathways from the Kyoto Encyclopedia of Genes and Genomes(KEGG). Enrichment and network analyses of protein-protein interactions predicted that CH significantly affected the PI3K/AKT signaling pathway, which played a critical role in programmed cell death. The core components and key targets showed strong binding activity based on molecular docking results. Subsequently, experimental validation demonstrated that CH inhibited the phosphorylation of PI3K and AKT in pancreatic tissues, promoted the apoptosis of pancreatic acinar cells, and further alleviated inflammation and histopathological damage to the pancreas in AP rats., Conclusion: Apoptosis of pancreatic acinar cells can be enhanced and the inflammatory response can be reduced through the modulation of the PI3K/AKT signaling pathway, resulting in the amelioration of pancreatic disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Jiang, Zhou, Yao, Wang, Liu, Zhang, Tang and Li.)

Background: Oxidative stress is a crucial factor contributing to the occurrence and development of secondary damage in spinal cord injuries (SCI), ultimately impacting the recovery process. α-lipoic acid (ALA) exhibits potent antioxidant properties, effectively reducing secondary damage and providing neuroprotective benefits. However, the precise mechanism by which ALA plays its antioxidant role remains unknown., Methods: We established a model of moderate spinal cord contusion in rats. Experimental rats were randomly divided into 3 distinct groups: the sham group, the model control group (SCI&#95;Veh), and the ALA treatment group (SCI&#95;ALA). The sham group rats were exposed only to the SC without contusion injury. Rats belonging to SCI&#95;Veh group were not administered any treatment after SCI. Rats of SCI&#95;ALA group were intraperitoneally injected with the corresponding volume of ALA according to body weight for three consecutive days after the surgery. Subsequently, three days after SCI, spinal cord samples were obtained from three groups of rats: the sham group, model control group, and administration group. Thereafter, total RNA was extracted from the samples and the expression of three sets of differential genes was analyzed by transcriptome sequencing technology. Real-time PCR was used to verify the sequencing results. The impact of ALA on oxidative stress in rats following SCI was assessed by measuring their total antioxidant capacity and hydrogen peroxide (H 2 O 2 ) content. The effects of ALA on rat recovery following SCI was investigated through Beattie and Bresnahan (BBB) score and footprint analysis., Results: The findings from the transcriptome sequencing analysis revealed that the model control group had 2975 genes with altered expression levels when compared to the ALA treatment group. Among these genes, 1583 were found to be upregulated while 1392 were down-regulated. Gene ontology (GO) displayed significant enrichment in terms of functionality, specifically in oxidative phosphorylation, oxidoreductase activity, and signaling receptor activity. The Kyoto encyclopedia of genes and genomes (KEGG) pathway was enriched in oxidative phosphorylation, glutathione metabolism and cell cycle. ALA was found to have multiple benefits for rats after SCI, including increasing their antioxidant capacity and reducing H 2 O 2 levels. Additionally, it was effective in improving motor function (such as 7 days after SCI, the BBB score for SCI&#95;ALA was 8.400 ± 0.937 compared to 7.050 ± 1.141 for SCI&#95;Veh) and promoting histological recovery after SCI (The results of HE demonstrated that the percentage of damage area in was 44.002 ± 6.680 in the SCI&#95;ALA and 57.215 ± 3.964 in the SCI&#95;Veh at the center of injury.). The sequence data from this study has been deposited into Sequence Read Archive (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE242507)., Conclusion: Overall, the findings of this study confirmed the beneficial effects of ALA on recovery in SCI rats through transcriptome sequencing, behavioral, as well histology analyses.

Globally, alcohol-associated liver disease (ALD) has become an increased burden for society. Disulfirams, Benzodiazepines (BZDs), and corticosteroids are commonly used to treat ALD. However, the occurrence of side effects such as hepatotoxicity and dependence, impedes the achievement of desirable and optimal therapeutic efficacy. Therefore, there is an urgent need for more effective and safer treatments. Hovenia dulcis is an herbal medicine promoting alcohol removal clearance, lipid-lowering, anti-inflammatory, and hepatoprotective properties. Hovenia dulcis has a variety of chemical components such as dihydromyricetin, quercetin and beta-sitosterol, which can affect ALD through multiple pathways, including ethanol metabolism, immune response, hepatic fibrosis, oxidative stress, autophagy, lipid metabolism, and intestinal barrier, suggesting its promising role in the treatment of ALD. Thus, this work aims to comprehensively review the chemical composition of Hovenia dulcis and the molecular mechanisms involved in the process of ALD treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Liu, Wang, Wu, Wei, Xue, Zou, Zhou, Chen and Li.)