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Abstract Mutations in the nuclear envelope (NE) protein lamin A/C (encoded by LMNA), cause a severe form of dilated cardiomyopathy (DCM) with early-onset life-threatening arrhythmias. However, molecular mechanisms underlying increased arrhythmogenesis in LMNA-related DCM (LMNA-DCM) remain largely unknown. Here we show that a frameshift mutation in LMNA causes abnormal Ca2+ handling, arrhythmias and disformed NE in LMNA-DCM patient-specific iPSC-derived cardiomyocytes (iPSC-CMs). Mechanistically, lamin A interacts with sirtuin 1 (SIRT1) where mutant lamin A/C accelerates degradation of SIRT1, leading to mitochondrial dysfunction and oxidative stress. Elevated reactive oxygen species (ROS) then activates the Ca2+/calmodulin-dependent protein kinase II (CaMKII)-ryanodine receptor 2 (RYR2) pathway and aggravates the accumulation of SUN1 in mutant iPSC-CMs, contributing to arrhythmias and NE deformation, respectively. Taken together, the lamin A/C deficiency-mediated ROS disorder is revealed as central to LMNA-DCM development. Manipulation of impaired SIRT1 activity and excessive oxidative stress is a potential future therapeutic strategy for LMNA-DCM.

Brugada syndrome (BrS) is a hereditary arrhythmia syndrome characterized by right bundle branch block on an electrocardiogram and persistent ST-segment elevation in the right precordial leads. In this study, we describe the establishment of an induced pluripotent stem cell (iPSC) line derived from a BrS patient carrying the novel heterogeneous missense mutation (c.3118G>C; p.G1040R) in the sodium channel protein type 5 subunit alpha (SCN5A) gene. Skin fibroblasts underwent reprogramming using a non-integrated Sendai viral method. Generated iPSC line exhibited embryonic stem cell-like morphology, maintained a normal karyotype, expressed pluripotency markers, and demonstrated the capacity to differentiate into three germ layers.

The fire plume behavior of over-ventilated compartment fire is believed to be related with the façade fire. When the fire plume is reattached to the façade wall, the combustible materials over building wall are potential to be ignited soon. To investigate the window spill fire plume trajectory of over-ventilated intermediate-scale compartment fires, a modeling of fire plume trajectory is set up by using the energy conservation equation and spread theory. The temperature history of over-ventilated compartment fire is conducted by using a 1.35 m (L) × 1.35 m (H) × 1.35 m (W) compartment with window opening aspect varied from 1.12 to 4.44 and HRR differed from 200 kW to 1000 kW. The temperature of fire plume is recorded by the thermocouple mesh and the IR camera. It shows that the modelling theory could be used to predict the shape of fire plume. It agrees well with experimental result. The heat release rate of compartment fire is found to impact little influence on the shape of fire plume regarding a fixed opening dimension. It could provide a reasonable method for fire plume trajectory prediction of the intermediate-scale enclosure fire under an over-ventilated condition.

The fire plume spilled from a window is believed to be one of the main fire sources with respect to a building façade fire, which happened previously in China. To have a deep understanding of vertical temperature distribution at window opening is of significance. In the current contribution, a series of compartment fire tests under over-ventilation were conducted with a 1.35 m × 1.35 m × 1.35 m compartment to clarify the critical discontinuity position (HD) by varying window opening sizes, opening aspect and heat release rate (HRR). Temperature history at the window openings were recorded by a thermocouple net. A theoretical calculation method of HD is detailed according to the compartment configuration. It is found that the critical discontinuity area is observed apparently along the window opening height, which has a big temperature difference. By the comparison of experimental and theoretical results, the constant comprehensive coefficient of 1.68, 1.92 and 3.85 of 300 kW, 600 kW and 900 kW are got for an engineered empirical prediction model are proposed, respectively. It provides an insight for the understanding of critical temperature discontinuity and reference for engineering calculations.

Abstract Background Distant metastasis is the major cause of lung adenocarcinoma (LUAD)-associated mortality. However, molecular mechanisms involved in LUAD metastasis remain to be fully understood. While the role of long non-coding RNAs (lncRNAs) in cancer development, progression, and treatment resistance is being increasingly appreciated, the list of dysregulated lncRNAs that contribute to LUAD pathogenesis is also rapidly expanding. Methods Bioinformatics analysis was conducted to interrogate publicly available LUAD datasets. In situ hybridization and qRT-PCR assays were used to test lncRNA expression in human LUAD tissues and cell lines, respectively. Wound healing as well as transwell migration and invasion assays were employed to examine LUAD cell migration and invasion in vitro. LUAD metastasis was examined using mouse models in vivo. RNA pulldown and RNA immunoprecipitation were carried out to test RNA–protein associations. Cycloheximide-chase assays were performed to monitor protein turnover rates and Western blotting was employed to test protein expression. Results The expression of the lncRNA LINC01559 was commonly upregulated in LUADs, in particular, in those with distant metastasis. High LINC01559 expression was associated with poor outcome of LUAD patients and was potentially an independent prognostic factor. Knockdown of LINC01559 diminished the potential of LUAD cell migration and invasion in vitro and reduced the formation of LUAD metastatic lesions in vivo. Mechanistically, LINC01559 binds to vimentin and prevents its ubiquitination and proteasomal degradation, leading to promotion of LUAD cell migration, invasion, and metastasis. Conclusion LINC01559 plays an important role in LUAD metastasis through stabilizing vimentin. The expression of LINC01559 is potentially an independent prognostic factor of LUAD patients, and LINC01559 targeting may represent a novel avenue for the treatment of late-stage LUAD.

Hypertrophic cardiomyopathy (HCM), characterized by left ventricular hypertrophy and preserved or increased left ventricular ejection fraction, is the most common autosomal dominant inherited cardiovascular disease. We generated a human induced pluripotent stem cell (hiPSC) line derived from a HCM patient who carried a heterozygous missense mutation in the myosin heavy chain 6 (MYH6) gene. With a non-integrated Sendai viral method, the patient-specific hiPSCs were generated from skin fibroblasts. We confirmed the stemness of the hiPSCs and its capability of differentiating into three germ layers. Meanwhile, the generated hiPSCs showed human embryonic stem cell-like morphology and normal karyotype.

Since its initial report in 2015, CD47 has garnered significant attention as an innate immune checkpoint, raising expectations to become the next “PD-1.” The optimistic early stages of clinical development spurred a flurry of licensing deals for CD47-targeted molecules and company mergers or acquisitions for related assets. However, a series of setbacks unfolded recently, starting with the July 2023 announcement of discontinuing the phase 3 ENHANCE study on Magrolimab plus Azacitidine for higher-risk myelodysplastic syndromes (MDS). Subsequently, in August 2023, the termination of the ASPEN-02 program, assessing Evorpacept in combination with Azacitidine in MDS patients, was disclosed due to insufficient improvement compared to Azacitidine alone. These setbacks have cast doubt on the feasibility of targeting CD47 in the industry. In this review, we delve into the challenges of developing CD47-SIRPα-targeted drugs, analyze factors contributing to the mentioned setbacks, discuss future perspectives, and explore potential solutions for enhancing CD47-SIRPα-targeted drug development.

IntroductionCultivation of Chinese fir (Cunninghamia lanceolata) have alleviated timber shortages and mixed stands with Chinese fir and indigenous species represent a sustainable forestry model. Studying system nutrient balance and tree nutrient homeostasis can provide insights into the ecological advantages of Chinese fir mixed stands and guide the management of plantations.MethodsMixed Chinese fir plantations with two native broadleaf species (Michelia macclurei and Mytilaria laosensis) and pure Chinese fir stands were examined for our study. The responses in carbon (C), nitrogen (N), and phosphorus (P) distribution and their stoichiometric characterization in the tree–litter–soil system to stand changes were evaluated. In addition, the ecological stoichiometric homeostasis of leaves, branches, trunks, bark and roots was used to measure the trees’ adaptive capacity to stand changes.ResultsThe results showed that the mixed stands of Michelia macclurei and Chinese fir significantly increased soil OC, TN, and TP, and improved the carbon sequestration and nutrient storage functions of the plantations. The mixed stands improved the litter mass and C:N and C:P to different degrees. The soil N and P imbalance reduced the leaf N:P, resulting in N limitation of different trees, while the principal component analysis showed that the improvement of soil TN in the mixed plantation alleviated the N limitation. In addition, mixed stands reduced N, P, and N:P homeostasis in branch, trunk, and bark of some Chinese fir trees, whereas mixed species showed flexibility in leaf N:P homeostasis.DiscussionTherefore, the selection of mixed species for mixed forests is a critical factor to consider when creating mixed plantations. These results contribute to our understanding of the ecological stoichiometry of fir plantations and are of considerable importance for the sustainable development of plantations as well as for the response to global climate change.

Abstract Polarized neutron scattering is an indispensable tool for exploring a vast range of scientific phenomena. With its dynamic scientific community and significant governmental support as well as the rapid economic growth, the Asia–Pacific region has become a key player in the worldwide neutron scattering arena. From traditional research reactors to cutting-edge spallation neutron sources, this region is home to a myriad of advanced instruments offering a wide range of polarized neutron capabilities. This review aims to provide a comprehensive overview of the development and current status of polarized neutron instruments and techniques in the Asia–Pacific region, emphasizing the important role of the Asia–Pacific region in shaping the landscape of global polarized neutron scattering development.

Abstract Background Mutations in the cardiac sodium channel gene SCN5A cause Brugada syndrome (BrS), an arrhythmic disorder that is a leading cause of sudden death and lacks effective treatment. An association between SCN5A and Wnt/β-catenin signaling has been recently established. However, the role of Wnt/β-catenin signaling in BrS and underlying mechanisms remains unknown. Methods Three healthy control subjects and one BrS patient carrying a novel frameshift mutation (T1788fs) in the SCN5A gene were recruited in this study. Control and BrS patient-specific induced pluripotent stem cells (iPSCs) were generated from skin fibroblasts using nonintegrated Sendai virus. All iPSCs were differentiated into cardiomyocytes using monolayer-based differentiation protocol. Action potentials and sodium currents were recorded from control and BrS iPSC-derived cardiomyocytes (iPSC-CMs) by single-cell patch clamp. Results BrS iPSC-CMs exhibited increased burden of arrhythmias and abnormal action potential profile featured by slower depolarization, decreased action potential amplitude, and increased beating interval variation. Moreover, BrS iPSC-CMs showed cardiac sodium channel (Nav1.5) loss-of-function as compared to control iPSC-CMs. Interestingly, the electrophysiological abnormalities and Nav1.5 loss-of-function observed in BrS iPSC-CMs were accompanied by aberrant activation of Wnt/β-catenin signaling. Notably, inhibition of Wnt/β-catenin significantly rescued Nav1.5 defects and arrhythmic phenotype in BrS iPSC-CMs. Mechanistically, SCN5A-encoded Nav1.5 interacts with β-catenin, and reduced expression of Nav1.5 leads to re-localization of β-catenin in BrS iPSC-CMs, which aberrantly activates Wnt/β-catenin signaling to suppress SCN5A transcription. Conclusions Our findings suggest that aberrant activation of Wnt/β-catenin signaling contributes to the pathogenesis of SCN5A-related BrS and point to Wnt/β-catenin as a potential therapeutic target.

The impacts of the successive planting of Eucalyptus on soil microbial communities and their underlying mechanisms remain unknown, limiting our understanding of its long-term effects on soil ecosystems. This study examined the 0–20 cm and 20–40 cm soil layers, investigating changes in soil bacterial and fungal communities after multiple plantings of Eucalyptus grandis × urophylla using high-throughput sequencing. Furthermore, we used the structural equation model (SEM) to analyze the relationships among soil active organic carbon (SAOC), enzyme activity, and microbial diversity. The study showed that the multigeneration successive planting of Eucalyptus significantly increased the soil bulk density and decreased the soil physicochemical properties and soil enzyme activities (p < 0.05). The soil’s dominant microbial compositions were unchanged in the two soil horizons, but the relative abundances of some dominant phyla (e.g., Crenarchaeota, Basidiomycota and Actinobacteriota) were affected by successive planting. The variability in the microbial community structure was influenced primarily by the soil water content (SWC) and organic carbon (p < 0.05). The microbial community diversity in the 20–40 cm horizon was significantly affected by multigeneration succession (p < 0.05). SWC was the core factor driving microbial community diversity. SEM results showed that multigeneration successive planting obviously limits SAOC fractions and enzyme activities, negatively affecting soil microbial diversity. Our study highlights the impact of the multigeneration successive planting of Eucalyptus on soil microbial community structure and suggests adjustments in forestry practices to mitigate soil degradation.

AbstractObjective: Given the psychosocial and ethical burden, patients with hypertrophic cardiomyopathy (HCMs) could benefit from the establishment of genetic probability prior to the test. This study aimed to develop a simple tool to provide genotype prediction for HCMs.Methods: A convolutional neural network (CNN) was built with the 12-lead electrocardiogram (ECG) of 124 HCMs who underwent genetic testing (GT), externally tested by predicting the genotype on another HCMs cohort (n = 54), and compared with the conventional methods (the Mayo and Toronto score). Using a third cohort of HCMs (n = 76), the role of the network in risk stratification was explored by calculating the sudden cardiac death (SCD) risk scorers (HCM risk-SCD) across the predicted genotypes. Score-CAM was employed to provide a visual explanation of the network.Results: Overall, 80 of 178 HCMs (45%) were genotype-positive. Using the 12-lead ECG as input, the network showed an area under the curve (AUC) of 0.89 (95% CI, 0.83–0.96) on the test set, outperforming the Mayo score (0.69 [95% CI, 0.65–0.78], p

IntroductionThe production of Eucalyptus, a principal economic tree genus in China, is faced with challenges related to soil phosphorus (P) limitations. In this study, we explore variations in phosphorus content, storage, and transformation in Eucalyptus forests. We hypothesize that mixed forests augment soil aggregate stability and P content and that microaggregates are pivotal in determining P differences between mixed and pure forests. Additionally, we posit that mixed forests foster P transformation, enhancing its efficacy in the soil. Current research on the distribution and transformation of soil total P (TP) and P fractions at the soil aggregate level is limited.MethodsIn this study, we selected soil from a Eucalyptus-Mytilaria laosensis Lecomte mixed forest, Eucalyptus-Erythrophleum fordii Oliv mixed forest, and pure Eucalyptus forest in Chongzuo County, Guangxi, China, as the research objects. Using a dry-sieving method, we divided the soil collected in situ from the 0–40 cm layer into aggregates of >2, 1–2, 0.25–1, and

Assessing the limitations of microbial metabolic resources is crucial for understanding plantation soil quality and enhancing fertility management. However, the variation of microbial resource limitations at the aggregate level in response to changes in stands remains unclear. This research explores carbon (C), nitrogen (N), and phosphorus (P) limitations affecting microbial metabolism in bulk soils and aggregates in two mixed and one pure Chinese fir stands in subtropical China, analyzing resource limitations concerning soil carbon, nutrients, and microbial indicators. The results revealed that microbes in all aggregates of the pure stands and in the micro aggregates (2 mm) and small aggregates (2–0.25 mm) in the mixed stands. Additionally, in the mixed stands the proportion of soil macroaggregates increased, and that of micro aggregates decreased, resulting in a shift from C and P limitation to N limitation for bulk soil microbial metabolism. Redundancy analysis identified soil aggregate organic carbon and nutrient content as the main factors affecting microbial resource limitation, rather than their stoichiometric ratios. Pathway analysis further confirmed that soil nutrients and their stoichiometric ratios indirectly influenced soil microbe resource limitation by regulating microbial biomass, microbial respiration, and extracellular enzyme activities. Thus, the impact of mixed plantations on soil nutrients and microbial activity at the aggregate level may be crucial for maintaining land fertility and achieving sustainability.

Mixed cultivation with legumes may alleviate the nitrogen (N) limitation of monoculture Eucalyptus. However, how leaf functional traits respond to N in mixed cultivation with legumes and how they affect tree growth are unclear. Thus, this study investigated the response of leaf functional traits of Eucalyptus urophylla × Eucalyptus grandis (E. urophylla × E. grandis) and Dalbergia odorifera (D. odorifera) to mixed culture and N application, as well as the regulatory pathways of key traits on seedling growth. In this study, a pot-controlled experiment was set up, and seedling growth indicators, leaf physiology, morphological parameters, and N content were collected and analyzed after 180 days of N application treatment. The results indicated that mixed culture improved the N absorption and photosynthetic rate of E. urophylla × E. grandis, further promoting seedling growth but inhibiting the photosynthetic process of D. odorifera, reducing its growth and biomass. Redundancy analysis and path analysis revealed that leaf nitrogen content, pigment content, and photosynthesis-related physiological indicators were the traits most directly related to seedling growth and biomass accumulation, with the net photosynthetic rate explaining 50.9% and 55.8% of the variation in growth indicators for E. urophylla × E. grandis and D. odorifera, respectively. Additionally, leaf morphological traits are related to the trade-off strategy exhibited by E. urophylla × E. grandis and D. odorifera based on N competition. This study demonstrated that physiological traits related to photosynthesis are reliable predictors of N nutrition and tree growth in mixed stands, while leaf morphological traits reflect the resource trade-off strategies of different tree species.

Summary: Background: Brugada syndrome (BrS) is a cardiac channelopathy that can result in sudden cardiac death (SCD). SCN5A is the most frequent gene linked to BrS, but the genotype–phenotype correlations are not completely matched. Clinical phenotypes of a particular SCN5A variant may range from asymptomatic to SCD. Here, we used comparison of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) derived from a SCN5A mutation-positive (D356Y) BrS family with severely affected proband, asymptomatic mutation carriers (AMCs) and healthy controls to investigate this variation. Methods: 26 iPSC lines were generated from skin fibroblasts using nonintegrated Sendai virus. The generated iPSCs were differentiated into cardiomyocytes using a monolayer-based differentiation protocol. Findings: D356Y iPSC-CMs exhibited increased beat interval variability, slower depolarization, cardiac arrhythmias, defects of Na+ channel function and irregular Ca2+ signaling, when compared to controls. Importantly, the phenotype severity observed in AMC iPSC-CMs was milder than that of proband iPSC-CMs, an observation exacerbated by flecainide. Interestingly, the iPSC-CMs of the proband exhibited markedly decreased Ca2+ currents in comparison with control and AMC iPSC-CMs. CRISPR/Cas9-mediated genome editing to correct D356Y in proband iPSC-CMs effectively rescued the arrhythmic phenotype and restored Na+ and Ca2+ currents. Moreover, drug screening using established BrS iPSC-CM models demonstrated that quinidine and sotalol possessed antiarrhythmic effects in an individual-dependent manner. Clinically, venous and oral administration of calcium partially reduced the malignant arrhythmic events of the proband in mid-term follow-up. Interpretation: Patient-specific and genome-edited iPSC-CMs can recapitulate the varying phenotypic severity of BrS. Our findings suggest that preservation of the Ca2+ currents might be a compensatory mechanism to resist arrhythmogenesis in BrS AMCs. Funding: National Key R&D Program of China (2017YFA0103700), National Natural Science Foundation of China (81922006, 81870175), Natural Science Foundation of Zhejiang Province (LD21H020001, LR15H020001), National Natural Science Foundation of China (81970269), Key Research and Development Program of Zhejiang Province (2019C03022) and Natural Science Foundation of Zhejiang Province (LY16H020002).

Transformers, being the largest oil-bearing equipment, are susceptible to high-temperature hot oil fires and large-area flowing fires that can be challenging to extinguish. To investigate the effectiveness of compressed air foams (CAFs) agents in extinguishing fires in ultra-high voltage (UHV) converter transformers, this work examines the fire suppression capabilities of three typical CAFs agents. A test model of a hot oil fire in a transformer with a burning area of 1 m2 was constructed for this purpose. The fire test was conducted by heating the transformer oil using an electric heating system, and the test process was monitored using an unmanned aerial vehicle. The results indicate that three CAFs agents used in the tests are capable of extinguishing a 1 m2 transformer hot oil fire without causing boiling over phenomenon. 1% MJBP CAFs is the fastest with a fire extinguishing time of 168 s, and is even more efficient when the gas to liquid ratio is 9:1. CAFs have the advantage of uniformity and stability, making it suitable for extinguishing hot oil fires in extra high voltage transformers as it does not cause boiling fires during firefighting.

Docetaxel is one of the most commonly used drugs in prostate cancer (PCa) chemotherapy, but its therapeutic effect in PCa is usually limited due to its drug resistance. APOBEC3B is a DNA cytosine deaminase that can alter biological processes, including chemoresistance. APOBEC3B is upregulated in various cancers. However, the biological function and underlying regulation of APOBEC3B in PCa remain unclear. In this study, we explored the role of APOBEC3B in PCa chemoresistance and the molecular mechanism of its dysregulated expression. Our results revealed that APOBEC3B was upregulated in PCa docetaxel-resistant cells, while its knockdown significantly repressed cell proliferation and docetaxel resistance of PCa cells. Bioinformatics and luciferase report analysis showed that miR-138–5p targeted APOBEC3B. In addition, miR-138–5p overexpression impeded cell proliferation and docetaxel resistance in PCa, while miR-138–5p inhibitors reversed this process. Further studies showed that upregulation of APOBEC3B expression in docetaxel-resistant cells overexpressing miR-138–5p could desensitize PCa cells to docetaxel treatment. Taken together, miR-138–5p regulates PCa cell proliferation and chemoresistance by targeting the 3′-UTR of APOBEC3B, which may provide novel insights and therapeutic targets for the treatment of PCa.

Abstract Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice. Inflammation plays an important role in the initiation and perpetuation of AF. The present study was conducted to characterize immune clusters in nonparoxysmal AF and to distinguish immune subtypes of nonparoxysmal AF. Immune-related algorithms (CIBERSORT, ESTIMATE, and ssGSEA) were used to evaluate the immune cluster characterization and cell abundance, and multivariable logistics analysis was performed to determine the most relevant immune cells. We identified differentially expressed genes (DEGs) and used consensus clustering analysis to identify nonparoxysmal AF subtypes. Weighted gene coexpression network analysis (WGCNA) was used for finding highly correlated gene sets and attach to external sample traits. And it was conducted twice to identify the immune- and subtype- related modules. Finally, Metascape was used to compare the biological functions of the two nonparoxysmal AF subtypes we obtained. CytoHubba was used to identify the hub genes of these two subtypes. Based on the results of bioinformatics analysis, regulatory T cells, resting NK cells, active mast cells and neutrophils were considered to be closely related to nonparoxysmal AF. The brown module was identified as the most relevant module to the above immune cells by WGCNA. We identified two major nonparoxysmal AF subtypes by consensus clustering analysis and their enriched biological functions by Metascape. The hub genes are TYROBP, PTPRC, ITGB2, SPI1, PLEK, and CSF1R in permanent AF and JAM3, S100P, ARPC5, TRIM34, and GREB1L in persistent AF. This study revealed two major nonparoxysmal AF subtypes and eleven hub genes, which provide potential therapeutic targets for anti-inflammatory treatments of nonparoxysmal AF.

Abstract. Background:. The Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score was developed in 2013 to predict survival in heart failure (HF) patients. However, it has yet to be validated in a Chinese population. Our study aimed to investigate the ability of the score to predict 1-year mortality in a Chinese population. Methods:. Consecutive patients with HF were retrospectively selected from the inpatient electronic medical records of the cardiology department in a regional hospital in China. A total integer score was calculated for each enrolled patient based on the value of each risk factor in the MAGGIC scoring system. Each enrolled patient was followed for at least 1 year. The observational endpoint of this study was all-cause mortality. The predictive ability of the MAGGIC score was assessed by comparing observed and predicted mortality within 1 year. Results:. Between January 2018 and December 2020, a total of 635 patients were included in the study: 57 (9.0%) of whom died within 1 year after discharge. The average age of all patients was 74.6 ± 11.2 years, 264 of them (41.6%) were male, and the average left ventricular ejection fraction was 50.7% ± 13.2%. The area under the receiver operating characteristic curve was 0.840 (95% confidence interval: 0.779, 0.901), which indicated a fair discriminatory ability of the score. The Hosmer–Lemeshow test result (χ2 = 12.902, degree of freedom = 8, P = 0.115) indicated that the MAGGIC score had good calibration. The decision curve analysis showed that the MAGGIC score yielded a good clinical net benefit and net reduction in interventions. Conclusions:. This validation of the MAGGIC score showed that it has a good ability to predict 1-year mortality in Chinese patients with HF after discharge. Due to regional and inter-hospital differences, external validation studies need to be further confirmed in other centers.

Background Toll-like receptors (TLRs) are important components of the innate and adaptive immune systems, and abnormal TLR expression has been linked to a variety of cancers. However, there was a lack of clarity on the association of TLR stimulation with the carcinogenesis of cancer. The study's goal was to analyse the clinical importance of TLRs expression at the mRNA level in pan-cancer datasets, as well as the link between TLR expression and carcinogenesis, progression, and clinical prognosis.Methods The expression profile of TLRs derived from UCSC pan-cancer data was analysed in multiple dimensions, including clinical analysis, immunological subtype analysis, tumour microenvironment (TME) analysis, tumour stem cell correlation analysis, and drug sensitivity analysis. Additionally, we analyse protein-protein interactions, functional enrichment, and chromatin accessibility, as well as TLR expression in single-cell sequencing data.Results Our multi-omics analysis results imply that TLRs may operate as a biological marker for carcinogenesis and progression, a potential target for anti-tumour therapy, and a prognostic biomarker, laying the theoretical groundwork for future translational medicine research.Conclusion TLRs are involved in the formation of malignancies and can be explored in further detail as potential prognostic indicators. Key MessagesToll-like receptors (TLRs) are key factors in the process of the innate and adaptive immune response, and their aberrant expression of TLRs have been widely reported in various cancer. However, the association between TLRs stimulation and tumorigenesis of cancer has not been well clarified.In this study, in the pan-cancer data, integrated TLR family gene expression analysis, clinical correlation analysis, immune subtype correlation analysis, tumour microenvironment correlation analysis, tumour stem cell correlation analysis, and drug sensitivity correlation analysis were performed.TLRs play an important role in the development of tumours and can be studied in depth as potential prognostic markers.

Research on the variations in soil aggregate stability and ecological stoichiometry at aggregate scales by stand type is of great significance in investigating the distribution, limitation, balance, and cycling of organic carbon, nitrogen, and phosphorus (C-N-P). However, the effect of pure and mixed Chinese fir plantations on soil aggregate stability, organic carbon (OC), total nitrogen (TN), and total phosphorus (TP) stoichiometry characteristics at aggregate scales is still unclear. In this research, we explored the variations in soil aggregate mean weight diameter (MWD) and geometric mean diameter (GMD); soil OC, TN, and TP contents and stocks and the C:N:P ratios as affected by different stand types (mixed stands of Chinese fir and Mytilaria laosensis, mixed stands of Chinese fir and Michelia macclurei, and pure stand of Chinese fir); and aggregate size (2 mm) at 0–20 and 20–40 cm depths in subtropical China. The soil OC and TN contents, as well as C:N:P ratios declined as aggregate size increased, whereas the C-N-P stocks showed the opposite tendencies, which were more distributed in >2 mm aggregates. Mixed stands of Chinese fir and M. laosensis with Chinese fir and M. macclurei displayed significantly higher soil aggregate stability, aggregate-associated TP content, OC and TN contents and stocks, and C:N and C:P ratios than did pure stands of Chinese fir. Soil aggregate stability was significantly positively correlated with the C-N-P contents and stocks as well as the C:N and C:P ratios, especially the C:N ratio and TN content. Overall, this work offers further information for scientific management and sustainable development of Chinese fir plantations, soil OC and nutrient cycling with ecological stoichiometry in the global terrestrial ecosystem.

Background: Calcific aortic valve stenosis (CAVS) is a crucial cardiovascular disease facing aging societies. Our research attempts to identify immune-related genes through bioinformatics and machine learning analysis. Two machine learning strategies include Least Absolute Shrinkage Selection Operator (LASSO) and Support Vector Machine Recursive Feature Elimination (SVM-RFE). In addition, we deeply explore the role of immune cell infiltration in CAVS, aiming to study the potential therapeutic targets of CAVS and explore possible drugs. Methods: Download three data sets related to CAVS from the Gene Expression Omnibus. Gene set variation analysis (GSVA) looks for potential mechanisms, determines differentially expressed immune-related genes (DEIRGs) by combining the ImmPort database with CAVS differential genes, and explores the functions and pathways of enrichment. Two machine learning methods, LASSO and SVM-RFE, screen key immune signals and validate them in external data sets. Single-sample GSEA (ssGSEA) and CIBERSORT analyze the subtypes of immune infiltrating cells and integrate the analysis with DEIRGs and key immune signals. Finally, the possible targeted drugs are analyzed through the Connectivity Map (CMap). Results: GSVA analysis of the gene set suggests that it is highly correlated with multiple immune pathways. 266 differential genes (DEGs) integrate with immune genes to obtain 71 DEIRGs. Enrichment analysis found that DEIRGs are related to oxidative stress, synaptic membrane components, receptor activity, and a variety of cardiovascular diseases and immune pathways. Angiotensin II Receptor Type 1(AGTR1), Phospholipid Transfer Protein (PLTP), Secretogranin II (SCG2) are identified as key immune signals of CAVS by machine learning. Immune infiltration found that B cells naï ve and Macrophages M2 are less in CAVS, while Macrophages M0 is more in CAVS. Simultaneously, AGTR1, PLTP, SCG2 are highly correlated with a variety of immune cell subtypes. CMap analysis found that isoliquiritigenin, parthenolide, and pyrrolidine-dithiocarbamate are the top three targeted drugs related to CAVS immunity. Conclusion: The key immune signals, immune infiltration and potential drugs obtained from the research play a vital role in the pathophysiological progress of CAVS.

Background: Previous studies have reported inconsistent results on the causal association between habitual tea consumption and the risk of cardiovascular disease (CVD). This study is aim to determine the association between habitual tea intake and CVD using two-sample Mendelian randomization (MR) analysis.Methods: The genetically predicted causation between tea consumption and 7 common cardiovascular diseases (atrial fibrillation, hypertension, acute myocardial infarction, coronary atherosclerosis, peripheral vascular disease, angina, and heart failure) was evaluated using MR analysis model. We performed a total of 9 MR analysis methods to analyze the final results. The IVW methods was used as the primary outcome. The other MR analysis method (simple mode, weighted mode, simple median, weighted median, penalized weighted median, MR Egger, and MR-Egger (bootstrap)) were performed as the complement to IVW. Also, the robustness of the MR analysis results was assessed using a leave-one-out analysis.Results: The IVW analysis methods indicated that there is no causal association between tea consumption and risk of CVD (AF: OR, 0.997, 95% CI, 0.992–1.0001, p = 0.142; hypertension: OR, 0.976, 95% CI, 0.937–1.017, p = 0.242; AMI: OR, 0.996, 95% CI, 0.991–1.000, p = 0.077; CA: OR, 1.001, 95% CI, 0.993–1.009, p = 0.854; PVD: OR, 1.002, 95% CI, 1.000–1.005, p = 0.096; angina: OR, 0.999, 95% CI, 0.993–1.006, p = 0.818; HF: OR, 0.999, 95% CI, 0.996–1.002, p = 0.338). The other MR analysis method and further leave-one-out sensitivity analysis suggested the results were robust.Conclusion: This MR study indicated that there was no genetically predicted causal association between habitual tea intake and risk of CVD.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited cardiovascular disease characterized by left ventricular hypertrophy and cardiomyocyte disarray. In this study, a skin biopsy was obtained from a HCM patient, who carried a missense mutation (c.4384G > A; p.E1462K) in the myosin heavy chain 7 (MYH7) gene. The skin fibroblasts were subsequently reprogrammed with a non-integrated Sendai viral method to generate a patient-specific induced pluripotent stem cell (iPSC) line. The generated iPSC line showed typical morphology and normal karyotype, expressed pluripotency markers, and was capable to differentiate into three germ layers.

BackgroundCardiac sympathetic nerve system (SNS) might play an important role in arrhythmogenesis of arrhythmogenic cardiomyopathy (ACM). This study aims to assess the activity of cardiac SNS in ACM patients by heart rate variability (HRV), and to investigate its predictive value for sustained ventricular tachycardia (sVT).MethodsA total of 88 ACM patients and 65 sex- and age- matched healthy participants were enrolled. The time domain measures were used to evaluate the activity of cardiac SNS. An independent cohort with 48 ACM patients was as the validation cohort.ResultsACM patients had lower levels of standard deviation of all NN intervals (SDNN) [118.0 (90.3, 136.8) vs. 152.0 (132.5, 174.5) ms, p < 0.001] compared with healthy participants. Further analysis showed ACM patients with sVT had lower levels of SDNN than those without sVT (105.0 ± 28.1 vs. 131.8 ± 33.1 ms, p < 0.001). Multivariate logistic regression analysis showed SDNN was independently associated with sVT in ACM patients [odds ratio (OR) 0.59, 95% confidence interval (CI) (0.45–0.78), p < 0.001]. Receiver operating characteristics curve demonstrated SDNN had clinical values in predicting sVT in ACM patients [area under the curve (AUC) = 0.73, 95% CI (0.63–0.84), p < 0.001], which was verified in the validation cohort.ConclusionThe present study suggests that HRV is impaired in patients with ACM, and the SDNN level has a moderate value in risk stratification for sVT in ACM patients. In addition, the finding might provide new target for the further management of ACM with integrated traditional Chinese and western medicine.

Hypertrophic cardiomyopathy (HCM) is an inherited cardiovascular disease characterized by left ventricular hypertrophy and a high risk of sudden death. In this study, a skin biopsy was obtained from a HCM patient harboring a heterozygous missense mutation (c.3764C>A; p.A1225D) in the myosin binding protein C3 (MYBPC3) gene. The isolated fibroblasts were reprogrammed using non-integrated Sendai viral method to establish the patient-specific induced pluripotent stem cell (iPSC) line. The established iPSC line displayed normal morphology and karyotype, expressed pluripotency markers, and can differentiate into three germ layers in vivo.

Catheter ablation (CA) is considered as one of the most effective methods technique for eradicating persistent and abnormal cardiac arrhythmias. Nevertheless, in some cases, these arrhythmias are not treated properly, resulting in their recurrences. If left untreated, they may result in complications such as strokes, heart failure, or death. Until recently, the primary techniques for diagnosing recurrent arrhythmias following CA were the findings predisposing to the changes caused by the arrhythmias on cardiac imaging and electrocardiograms during follow-up visits, or if patients reported having palpitations or chest discomfort after the ablation. However, these follow-ups may be time-consuming and costly, and they may not always determine the root cause of the recurrences. With the introduction of artificial intelligence (AI), these follow-up visits can be effectively shortened, and improved methods for predicting the likelihood of recurring arrhythmias after their ablation procedures can be developed. AI can be divided into two categories: machine learning (ML) and deep learning (DL), the latter of which is a subset of ML. ML and DL models have been used in several studies to demonstrate their ability to predict and identify cardiac arrhythmias using clinical variables, electrophysiological characteristics, and trends extracted from imaging data. AI has proven to be a valuable aid for cardiologists due to its ability to compute massive amounts of data and detect subtle changes in electric signals and cardiac images, which may potentially increase the risk of recurrent arrhythmias after CA. Despite the fact that these studies involving AI have generated promising outcomes comparable to or superior to human intervention, they have primarily focused on atrial fibrillation while atrial flutter (AFL) and atrial tachycardia (AT) were the subjects of relatively few AI studies. Therefore, the aim of this review is to investigate the interaction of AI algorithms, electrophysiological characteristics, imaging data, risk score calculators, and clinical variables in predicting cardiac arrhythmias following an ablation procedure. This review will also discuss the implementation of these algorithms to enable the detection and prediction of AFL and AT recurrences following CA.

Objective: Symptom-driven electrocardiogram (ECG) recording plays a significant role in the detection of post-ablation atrial fibrillation recurrence (AFR). However, making timely medical contact whenever symptoms occur may not be practical. Herein, a deep learning (DL)-based handheld device was deployed to facilitate symptom-driven monitoring. Methods: A cohort of patients with paroxysmal atrial fibrillation (AF) was trained to use a DL-based handheld device to record ECG signals whenever symptoms presented after the ablation. Additionally, 24-hour Holter monitoring and 12-lead ECG were scheduled at 3, 6, 9, and 12 months post-ablation. The detection of AFR by the different modalities was explored. Results: A total of 22 of 67 patients experienced AFR. The handheld device and 24-hour Holter monitor detected 19 and 8 AFR events, respectively, five of which were identified by both modalities. A larger portion of ECG tracings was recorded for patients with than without AFR [362(330) vs. 132(133), P=0.01)], and substantial numbers of AFR events were recorded from 18:00 to 24:00. Compared to Holter, more AFR events were detected by the handheld device in earlier stages (HR=1.6, 95% CI 1.2–2.2, P

Long QT syndrome (LQT) is an inherited primary arrhythmic disorder characterized by prolonged QT interval on the surface electrocardiogram and life-threatening arrhythmia. In this study, a skin biopsy was obtained from an LQT type 2 (LQT2) patient, who carried a nonsense mutation (c.1956C > A; p.Y652X) in the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene. The skin fibroblasts were reprogrammed by non-integrated Sendai viral method to generate a patient-specific induced pluripotent stem cell (iPSC) line. The generated iPSC line showed typical embryonic stem cell-like morphology, exhibited normal karyotype, expressed pluripotency markers, and was capable to differentiate into three germ layers.

AimsWe sought to investigate the relationship of left atrial appendage (LAA) mechanical dispersion (MD) with LAA dense spontaneous echo contrast (SEC) or thrombus, and to compare its usefulness in the identification of thrombogenesis with left atrial (LA) MD or LA/LAA strain parameters in patients with atrial fibrillation (AF).MethodsWe conducted a cross-sectional study of 493 consecutive patients with AF [65(58.5–71.0) years, male 66.9%] who underwent echocardiography prior to catheter ablation. We measured the LAA and LA global longitudinal strain (GLS) using speckle-tracking echocardiography (STE). LAA MD and LA MD was defined as the standard deviation (SD) of time to peak positive strain corrected by the R-R interval.ResultsPatients with LAA dense SEC/thrombus (n = 70) had significantly higher LAA MD than controls (n = 423) [median 14.2(11.6–16.8)% vs 9.4(6.2–12.1)%, p < 0.01]. Multivariable analysis showed that LAA MD was independently associated with LAA dense SEC/thrombus in four different models (Odds ratio, 1.23–1.24; p < 0.01), and provided additional diagnostic value over clinical and standard echocardiographic parameters. Whereas, LA MD was not independently associated with LAA dense SEC/thrombus and had no incremental value over other LA/LAA mechanical parameters.ConclusionLAA mechanical dispersion was an independent determinant of LAA dense SEC/thrombus in AF patients, incremental to conventional risk factors and superior to LA mechanical dispersion.

Osteoarthritis (OA) is the most common joint disease, usually occurring in middle-aged and elderly people. However, current treatment for OA in its early stages is ineffective, and drug therapy is often ineffective in slowing the progression of the disease. In fact, a deeper understanding of the underlying molecular mechanisms of OA could help us to better develop effective therapeutic measures. N6-methyladenosine (m6A) is a methylation that occurs at the adenosine N6-position, which is the most common internal modification on eukaryotic mRNAs. The role and mechanisms of m6A in mammalian gene regulation have been extensively studied. The “Writer”, “eraser”, and “reader” proteins are key proteins involved in the dynamic regulation of m6A modifications. Recent studies on post-transcriptional regulation alone have shown that m6a modification has an important role in the development of OA. This paper summarizes the specific regulatory processes of M6A in disease and reviews the role of m6A in OA, describing its pathophysiological role and molecular mechanisms, as well as its future research trends and potential clinical applications in OA.

Abstract Objective Recent studies demonstrated cutaneous phosphorylated α synuclein (p‐syn) deposition in idiopathic and some monogenetic Parkinson disease (PD) patients, suggesting synucleinopathy identical to that in the brain. Although the LRRK2 Gly2385Arg (G2385R) variant is a common PD risk factor in the Chinese population, the pathogenesis of PD with G2385R variant has not been reported. We investigated whether synucleinopathy and small fiber neuropathy (SFN) are associated with the G2385R variant. Methods We performed genotyping in 59 PD patients and 30 healthy controls from the skin biopsy database. The scale of SFN was assessed, as well as bright‐field immunohistochemistry against antiprotein gene product 9.5 (PGP9.5) and double‐labeling immunofluorescence with anti‐PGP9.5 and anti‐p‐syn. Results (1) p‐syn deposited in the skin nerve fibers of G2385R carrier PD patients, which was a different pattern from noncarriers, without no difference observed between proximal and distal regions; (2) decreased distal intraepidermal nerve fiber density was found in both the G2385R carrier and the noncarrier PD group, and was negatively correlated with composite autonomic symptom score‐31 item (COMPASS‐31) scores; (3) PD patients with the G2385R variant showed a more peculiar clinical profile than noncarriers with a higher nonmotor symptoms scale, COMPASS‐31 score, and levodopa equivalent dose, in addition to an increased prevalence of certain autonomic symptoms or rapid eye movement sleep behavior disorders. Interpretation Synucleinopathy is related to the LRRK2 G2385R genotype and implies a different pathogenesis in G2385R variant carriers and noncarriers. This study also extended the clinical profiles of PD patients with the G2385R variant.

Nitrogen plays a crucial role in limiting plant growth and determining net primary productivity in forest ecosystems. However, variations and influencing factors of soil nitrogen distribution on the aggregate scale in pure and mixed Chinese fir (Cunninghamia lanceolata (Lamb.) Hook) plantations remain unclear. This study aimed to explore how soil aggregate composition, geometric mean diameter (GMD), mean weight diameter (MWD), total nitrogen (TN), total acidolyzable nitrogen (TAN), available nitrogen (AN), nonacidolyzable nitrogen (AIN), amino acid nitrogen (AAN), nitrate nitrogen (NO3−-N), cidolyzable ammonia nitrogen (AMN), unknown-acidolyzable nitrogen (HUN), amino sugar nitrogen (ASN), and ammonium nitrogen (NH4+-N) contents and stocks varied with aggregate size (>2, 1–2, 0.25–1, and Michelia macclurei Dandy (CF + MM), Chinese fir mixed with Mytilaria laosensis Lecomte (CF + ML) and pure stands of Chinese fir (CF)] in 0–20 and 20–40 cm soil depth. Soil N content in different stand types of Chinese fir plantations decreased as the aggregate size increased, whereas the soil N stock exhibited the opposite trend. In contrast to CF soil, CF + MM and CF + ML soil displayed a significant increase in MWD, GMD, and aggregate-associated TN, AN, NO3−-N, NH4+-N, AIN, AAN, ASN, and AMN contents and stocks, especially CF + MM soil. Organic N was more sensitive to the response of aggregate size and stand type than mineral N. Redundancy analysis and Pearson’s correlation analysis indicated that the 0.25–1 mm aggregate proportion was the main controlling factor for the variations in soil N content and storage. Overall, this study contributed significantly to the promotion of the sustainable use of soil resources and reference information for the scientific management and sustainable development of Chinese fir forests.

Abstract Background Left atrial (LA) and left atrial appendage (LAA) dysfunction has been demonstrated to contribute to atrial fibrillation (AF)-related stroke. However, usefulness of LA and LAA mechanics has not been fully compared. We sought to investigate the association of LA and LAA mechanics with stroke and to compare their diagnostic values in the risk stratification of stroke in patients with nonvalvular AF. Methods A total of 208 consecutive patients with AF (63.58 ± 10.37 years, 63.9% male,57.7% persistent AF) who underwent echocardiography before catheter ablation were prospectively enrolled. Speckle-tracking was used to measure LA and LAA global longitudinal strain (GLS). LA and LAA mechanical dispersions (MD) were defined as the standard deviation (SD) of time to peak positive strain corrected by the R-R interval. Results Patients with prior stroke/ transient ischemic attack (TIA) (n = 31) had significantly higher LA and LAA MD than those without (n = 177) (11.56 ± 4.38% vs. 8.43 ± 3.44%, 15.15 ± 5.46% vs. 10.94 ± 4.40%, both P

Abstract Background Postoperative atrial fibrillation (POAF) is one of the most common complications of esophagectomy, which may extend the inpatient hospital stay. Minimally invasive esophagectomy (MIE) has been increasingly used in clinical practice; however, its POAF risk and short-term mortality remain unclear. This study aimed to examine the POAF risk and in-hospital mortality rate between patients receiving MIE and open esophagectomy (OE). Methods Esophageal cancer patients who underwent MIE or OE from a retrospective cohort study were evaluated. A multivariate logistic regression model was built to assess the associations between esophagectomy (MIE vs. OE) and various outcomes (POAF, in-hospital mortality). Covariates included age, sex, body mass index, neoadjuvant therapy, tumor stage, surgery incision type, comorbidities, cardia conditions, peri-operative medication, and complications. Results Of the 484 patients with esophageal cancer, 63 received MIE. A total of 53 patients developed POAF. Compared to patients receiving OE, MIE patients had 81% reduced odds of POAF (adjusted odds ratio [aOR] 0.185, 95% CI 0.039–0.887, P = 0.035). No statistically significant association was found for in-hospital mortality (aOR 0.709, 95% CI 0.114–4.409, P = 0.712). Conclusions MIE is associated with a lower risk of POAF, compared to traditional surgery. No significant short-term survival benefit was found for MIE.

Abstract Left bundle branch pacing was associated with narrower QRS in patients with pacemaker indications. LBBP guided by ICE improves the accuracy of LBBP, facilitates the lead localization, minimizes complications, and above all reduces radiation exposure time.

The remodeling of the left atrial morphology and function caused by atrial fibrillation (AF) can exacerbate thrombosis in the left atrium (LA) even spike up the risk of stroke within AF patients. This study explored the effect of the AF on hemodynamic and thrombosis in LA. We reconstructed the patient-specific anatomical shape of the LA and considered the non-Newtonian property of the blood. The thrombus model was applied in the LA models to simulate thrombosis. Our results indicate that AF can aggravate thrombosis which mainly occurs in the left atrial appendage (LAA). Thrombosis first forms on the LAA wall then expands toward the internal LAA. The proposed computational model also shows the potential application of numerical analyses to help assess the risk of thrombosis in AF patients.

Objective. This study is aimed at integrating bioinformatics and machine learning to determine novel diagnostic gene signals in the progression of heart failure disease. Methods. The heart failure microarray datasets and RNA-seq datasets have been downloaded from the public database. Differentially expressed genes (DE genes) are screened out, and then, we analyze their biological functions and pathways. Integrating three machine learning methods, the least absolute shrinkage and selection operator (LASSO) algorithm, random forest (RF) algorithm, and support vector machine recursive feature elimination (SVM-RFE) are used to determine candidate diagnostic gene signals. Then, external independent RNA-seq datasets evaluate the diagnostic value of gene signals. Finally, the convolution tool CIBERSORT estimated the composition pattern of immune cell subtypes in heart failure and carried out a correlation analysis combined with gene signals. Results. Under the set threshold, we obtained 47 DE genes with the most significant differences. Enrichment analysis shows that most of them are related to hypertrophy, matrix structural constituent, protein binding, inflammatory immune pathway, cardiovascular disease, and inflammatory disease. Three machine learning methods assisted in determining the potential characteristic signals Fras1-related extracellular matrix 1 (FREM1) and meiosis-specific nuclear structural 1 (MNS1). Validation of external datasets confirms that FREM1 is a diagnostic gene signal for heart failure. Immune cell subtypes of tissue specimens found T cell CD8, mast cell resting, T cell CD4 memory resting, T cell regulation (Tregs), monocytes, macrophages M2, T cell CD4 naive, macrophages M0, and neutrophils are associated with HF. Conclusion. The gene signal FREM1 may be a potential molecular target in the development of HF and is related to the difference in immune infiltration of HF tissue.

Introduction: Septal mass reduction is beneficial for hypertrophic obstructive cardiomyopathy (HOCM) patients with severe left ventricular outflow (LVOT) gradient and symptoms, with surgical myectomy or alcohol septal ablation (ASA) currently recommended in selected patients. Radiofrequency (RF) ablation of hypertrophied septum has been published as a novel method to alleviate LVOT obstruction in small populations. This study aims to investigate factors influencing clinical outcomes of radiofrequency septum ablation.Methods and Results: In this study, 20 patients with HOCM who underwent endocardial ablation were included. Echocardiography and cardiac MRI (CMR) data was collected and analyzed pre- and (or) post- procedure. Nineteen patients underwent ablation successfully, while ablation was aborted in one patient with prior RBBB due to transient complete atrioventricular block (AVB). After 6 months of follow-up, NYHA heart functional class improved from III (2 - 3) to II (1 - 2) (p < 0.001), and resting LVOT gradient was significantly reduced (87.6 ± 29.5 mmHg vs. 48.1 ± 29.7, p < 0.001). LVOT gradient reduction was significantly higher in patients with limited basal septal hypertrophy (60.9 ± 8.3 vs. 27.9 ± 7.1, p = 0.01), shorter anterior mitral leaflet (56.1 ± 6.4 vs. 20.4 ± 5.0, p < 0.01), and normally positioned papillary muscle (36.9 ± 7.1 vs. 75.0 ± 6.3, p < 0.05).Conclusions: Endocardial septal ablation appears to be a safe and effective procedure for alleviating LVOT gradient in patients with HOCM, especially in those with limited basal septal hypertrophy, shorter anterior mitral leaflet, and normal positioned papillary muscle.

Background: Ventricular arrhythmias are associated with sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). Previous studies have found the late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) was independently associated with ventricular arrhythmia (VA) in HCM. The risk stratification of VA remains complex and LGE is present in the majority of HCM patients. This study was conducted to determine whether the scar heterogeneity from LGE-derived entropy is associated with the VAs in HCM patients.Materials and Methods: Sixty-eight HCM patients with scarring were retrospectively enrolled and divided into VA (31 patients) and non-VA (37 patients) groups. The left ventricular ejection fraction (LVEF) and percentage of the LGE (% LGE) were evaluated. The scar heterogeneity was quantified by the entropy within the scar and left ventricular (LV) myocardium.Results: Multivariate analyses showed that a higher scar [hazard ratio (HR) 2.682; 95% CI: 1.022–7.037; p = 0.039] was independently associated with VA, after the adjustment for the LVEF, %LGE, LV maximal wall thickness (MWT), and left atrium (LA) diameter.Conclusion: Scar entropy and %LGE are both independent risk indicators of VA. A high scar entropy may indicate an arrhythmogenic scar, an identification of which may have value for the clinical status assessment of VAs in HCM patients.

Background: The substrate for ventricular tachycardia (VT) in patients with structural heart disease is usually complex and often requires extensive ablation. As a result, the incidence of major procedure-related complications has been reported to be higher when compared to patients without structural heart disease. In this study, we present a rare complication after extensive substrate modification of scar-related VT.Case: A 65-year-old man with ischemic cardiomyopathy was referred to the electrophysiology laboratory for radiofrequency ablation of VT following repetitive implantable cardioverter defibrillator shocks within a short period. As with hemodynamic intolerance of induced VT, an approach involving extensive endocardial substrate modification to reduce the arrhythmogenicity of the scars was adopted. After the procedure, the heart function of the patient deteriorated significantly. The postprocedural ECG showed a bizarre, extremely wide surface QRS complex (360 ms), termed as homologous ventricular separation. The pronounced dyssynchrony of the ventricle was corrected by an upgrade to cardiac resynchronization therapy with defibrillation (CRT-D). As a result, the symptoms of the patient improved significantly. The width of the intrinsic QRS complex was not recovered during an 18-month follow-up.Conclusion: Homologous ventricular separation is a rare arrhythmia, manifested as two separated QRS waves. This case report demonstrates, for the first time, that homologous ventricular separation may occur after extensive substrate modification of scar-related VT. CRT-D can correct the dyssynchronous ventricle caused by homologous ventricular separation.

Both specific and innate immune responses play important roles in autoimmune encephalitis (AE). We aimed to explore the predictive value of the systemic inflammation index (SII) at admission as a peripheral biomarker of treatment response of AE. A total of 146 patients diagnosed with AE in the First Affiliated Hospital of Zhengzhou University from January 1, 2018 to September 22, 2020 were retrospectively and consecutively analyzed as per the inclusion criteria and divided into two groups according to their response to immunotherapy after 30 days. The predictive value of the SII as a peripheral biomarker for AE treatment response was calculated using the receiver operating characteristic curve analysis, which showed that the best SII cut-off value for predicting poor response to AE treatment was 863.3; the area under the curve was 0.75, with 83.0% sensitivity and 72.0% specificity. The risk factors for poor response to AE treatment were analyzed; univariable analysis showed that the rate of decreased level of consciousness, rate of cognitive or mental behavior abnormality, cerebrospinal fluid pressure, blood neutrophils, platelets, time until treatment initiation, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and SII were significantly higher in patients with poor response to AE immunotherapy after 30 days than in patients with good response. Meanwhile, the blood lymphocyte counts and Glasgow Coma Scale (GCS) scores in patients with poor response were significantly lower than those in patients with good response (all p < 0.05), and multivariable binary logistic regression with backward stepwise method showed that decreased levels of consciousness, time until treatment initiation and SII were associated with poor response to immunotherapy. Moreover, the SII ≤ 863.3 group had lower rates of decreased consciousness levels, admission to the intensive care unit, and mechanical ventilation; lower cerebrospinal fluid pressure, blood neutrophil count, and platelet count; and higher blood lymphocyte count and GCS scores. The SII was associated with worsened disease severity and poor response to treatment after 30 days of the initially diagnosed AE, and patients with an SII > 863.3 were more likely to have poor response to immunotherapy.

Background: A non-invasive predictive model has not been established to identify the severity of coronary lesions in young adults with acute coronary syndrome (ACS). Methods: In this retrospective study, 1088 young adults (≤45 years of age) first diagnosed with ACS who underwent coronary angiography were enrolled and randomized 7:3 into training or testing datasets. To build the nomogram, we determined optimal predictors of coronary lesion severity with the Least Absolute Shrinkage and Selection Operator and Random Forest algorithm. The predictive accuracy of the nomogram was assessed with calibration plots, and performance was assessed with the receiver operating characteristic curve, decision curve analysis and the clinical impact curve. Results: Seven predictors were identified and integrated into the nomogram: age, hypertension, diabetes, body mass index, low-density lipoprotein cholesterol, mean platelet volume and C-reactive protein. Receiver operating characteristic analyses demonstrated the nomogram’s good discriminatory performance in predicting severe coronary artery disease in young patients with ACS in the training (area under the curve 0.683, 95% confidence interval [0.645–0.721]) and testing (area under the curve 0.670, 95% confidence interval [0.611–0.729]) datasets. The nomogram was also well-calibrated in both the training (P=0.961) and testing (P=0.302) datasets. Decision curve analysis and the clinical impact curve indicated the model’s good clinical utility. Conclusion: A simple and practical nomogram for predicting coronary artery disease severity in young adults≤45 years of age with ACS was established and validated.

Background: Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC), and Crohn's disease (CD), has been reported to be associated with an increased risk of atrial fibrillation (AF). However, the causal role of the chronic intestinal inflammation (CII) in the development of AF remains controversial. We use Mendelian randomization (MR) analysis to explore the causal inference of CII on AF.Methods: A two-sample MR analysis was performed to estimate the potential causal effect of CII on AF. Statistical summaries for the associations between single nucleotide polymorphisms (SNPs) and phenotypes of CII were obtained from genome-wide association studies (GWAS) with cohorts of CD (n = 51,874), UC (n = 47,745), and IBD (n = 65,642) of European descent. The GWAS of 1,030,836 people of European ancestry, including 60,620 AF cases and 970,216 controls was collected to identify genetic variants underlying AF. The causal inference was estimated using the multiplicative random effects inverse-variance weighted method (IVW). The methods of MR-Egger, simple median, and weighted median were also employed to avoid the bias of pleiotropy effects.Results: Using three sets of SNPs (75 SNPs of CD, 60 SNPs of UC, and 95 SNPs of IBD), multiplicative random-effect IVW model estimated a universal null effect of CII on AF (CD: OR = 1.0059, 95% CI: 0.9900, 1.0220, p = 0.47; UC: OR = 1.0087, 95% CI: 0.9896, 1.0281, p = 0.38; IBD: OR = 1.0080, 95% CI: 0.9908, 1.0255, p = 0.37). Similar results were observed using the MR-Egger, simple median, weighted median methods.Conclusion: As opposing to the traditional observational studies, our two-sample MR analysis did not find enough evidence to support a causal role of either CD or UC in the development of AF.

Objective: This study aimed to evaluate the potential association between uric acid (UA) lowering and cardiovascular risk reduction among UA-lowering therapies in adults.Methods: A systematic search for randomized controlled trials (RCTs) was conducted according to the protocol pre-registered in PROSPERO (No. CRD42020199259). We search for RCTs in PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov up to July 1, 2020. A meta-analysis was performed using a fixed- or random-effects model.Results: In total, 30 studies involving 18,585 hyperuricaemic patients were included. Xanthine oxidase inhibitor (XOI) therapy produced a 6.0% reduction in relative risk (RR) for major adverse cardiovascular events (MACEs). The use of febuxostat was associated with a higher risk of cardiovascular events (CVEs) (RR: 1.09, 95% CI 0.998–1.19, I2 = 0.0%), but the difference was not statistically significant. Allopurinol treatment was associated with a lower CVE risk (RR: 0.61, 95% CI 0.46–0.80, I2 = 21.0%). Among the UA-lowering therapies, the drug treatments were associated with all-cause mortality (RR: 1.20, 95% CI 1.02–1.41, I2 = 0.0%). The subgroup with a UA endpoint

Aims: Postoperative Atrial fibrillation (POAF) after esophagectomy may prolong stay in intensive care and increase risk of perioperative complications. A minimally invasive approach is becoming the preferred option for esophagectomy, yet its implications for POAF risk remains unclear. The association between POAF and minimally invasive esophagectomy (MIE) was examined in this study. Methods: We used a dataset of 575 patients who underwent esophagectomy. Multivariate logistic regression analysis was performed to examine the association between MIE and POAF. A cox proportional hazards model was applied to assess the long-term mortality (MIE vs open esophagectomy, OE). Results: Of the 575 patients with esophageal cancer, 62 developed POAF. MIE was negatively associated with the occurrence of POAF (Odds ratio: 0.163, 95%CI: 0.033-0.801). No significant difference was observed in long-term mortality (Odds ratio: 2.144, 95%CI: 0.963-4.775). Conclusions: MIE may reduced the incidence of POAF without compromising the survival of patients with esophageal cancer. Moreover, the specific mechanism of MIE providing this possible advantage needs to be determined by larger prospective cohort studies with specific biomarker information from laboratory tests.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease in which the right ventricular myocardium is replaced by progressive fibrous adipose tissue. ARVC is clinically characterized by right ventricular enlargement, ventricular arrhythmia, and sudden cardiac death. It eventually leads to heart failure, and thus has a significant impact on the patient's health. In this study, human dermal fibroblasts were obtained from a patient with ARVC, which were subsequently reprogrammed with a non-integrated Sendai virus to generate a patient-specific induced pluripotent stem cell (iPSC) line. The iPSC line exhibited normal karyotype and morphology, expressed pluripotency markers, and was capable of differentiating into three germ layers.