Identifying pyroptosis- and inflammation-related genes in intracranial aneurysms based on bioinformatics analysis.

BACKGROUND: Intracranial aneurysm (IA) is the most common cerebrovascular disease, and subarachnoid hemorrhage caused by its rupture can seriously impede nerve function. Pyroptosis is an inflammatory mode of cell death whose underlying mechanisms involving the occurrence and rupture of IAs remain unclear. In this study, using bioinformatics analysis, we identified the potential pyroptosis-related genes (PRGs) and performed their inflammatory response mechanisms in IAs. METHODS: The mRNA expression matrix of the IA tissue was obtained from the Gene Expression Omnibus database, and 51 PRGs were obtained from previous articles collected from PubMed. The differentially expressed PRGs (DEPRGs) were performed using R software. Subsequently, we performed enrichment analysis, constructed a protein-protein interaction network, performed weighted gene coexpression network analysis (WGCNA) and external validation using another dataset, and identified a correlation between hub genes and immune cell infiltration. Finally, the expression and tissue distribution of these hub genes in IA tissues were detected using Western blotting and immunohistochemical (IHC) staining. RESULTS: In total, 12 DEPRGs associated with IA were identified in our analysis, which included 11 up-regulated and one down-regulated genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the DEPRGs were mostly enriched in the NOD-like receptor signaling pathway, interleukin-1 beta production, and the inflammasome complex. Three hub genes, NLRP3, IL1B and IL18, were identified using Cytoscape software and the WGCNA correlation module, and external validation revealed statistically significant differences between the expression of these hub genes in the ruptured and unruptured aneurysm groups (p < 0.05). Furthermore, all AUC values were > 0.75. Immune cell infiltration analysis suggested that the hub genes are related to CD8 T cell, macrophages and mast cells. Finally, IHC staining revealed that the protein levels of these hub genes were higher in ruptured and unruptured IA tissues than in normal tissues (p < 0.05). CONCLUSION: The results of bioinformatics analysis showed that pyroptosis is closely related to the formation and rupture of IA, and identified three potential hub genes involved in the pyroptosis and infiltration ofcells. Our findings may improve the understanding of the mechanisms underlying pyroptosis in IA.

Compassion fatigue among haemodialysis nurses in public and private hospitals in China.

AIM: This study was conducted to identify and compare the levels of compassion fatigue and job satisfaction among haemodialysis nurses in public and private hospitals in China and explore explanatory factors based on sociodemographic and occupational characteristics. METHODS: A descriptive study was conducted using a self-designed demographic questionnaire, the Professional Quality of Life Scale and the Minnesota Satisfaction Questionnaire, with responses from 283 haemodialysis nurses working at six public and private hospitals in China between June and November 2018. RESULTS: The compassion fatigue score of public hospital nurses was significantly higher than that of private hospital nurses. Univariate analysis showed that there were significant differences in compassion fatigue among nurses based on the number of years worked, nature of employment, and education level. Correlational analysis showed a negative correlation between overall job satisfaction and compassion fatigue in both public and private hospitals. Multiple regression analysis showed that compassion fatigue among haemodialysis nurses in public hospitals was associated with years worked, type of employment, and intrinsic and extrinsic satisfaction, whereas in private hospitals, education level, years worked, and intrinsic and extrinsic satisfaction were significant. CONCLUSION: Haemodialysis nurses in public hospitals are more likely to develop compassion fatigue than those in private hospitals.

Polyurethanes Based on Unmodified and Refined Technical Lignins: Correlation between Molecular Structure and Material Properties.

The structural complexity and robust intermolecular interactions have challenged the incorporation of technical lignin into value-added polymeric materials for decades. To study the correlation between lignin molecular structure and material properties of lignin-based polyurethanes, we applied co-solvent enhanced lignocellulosic fractionation pretreatment followed by sequential precipitation to produce three distinct lignin preparations with narrowly distributed (molecular weight dispersity <2) and comparatively low molecular weight (<1500 g/mol) from poplar biomass. Structural characterization indicated that these lignin preparations differed in average molecular chain length and stiffness as well as hydroxyl group distribution. Secondary hydroxyl group providers such as aliphatic diols and polyethers were incorporated as building blocks into the lignin-based polyurethanes to provide additional hydrogen capacity to improve the dispersion of lignin in the polyurethane network. The selected aliphatic diols and polyethers interacted with lignin molecules at different levels of strength depending on their molecular structure, and their impacts were ultimately reflected in the mechanical and thermal properties of the resulting lignin-based polyurethanes. The copolymerization of technical lignin with tailored structure and secondary hydroxyl providers could provide new strategies in formulating lignin-based/containing polyurethanes for various functional applications.

Lignin-Only Polymeric Materials Based on Unmethylated Unfractionated Kraft and Ball-Milled Lignins Surpass Polyethylene and Polystyrene in Tensile Strength.

Functional polymeric materials composed solely of lignin preparations appeared only very recently. A gradual paradigm shift spanning 56 years has revealed how lignin-lignin blends can upgrade the performance of 100 wt% lignin-based plastics. The view, first espoused in 1960, that lignin macromolecules are crosslinked reduces the plausibility of creating functional polymeric materials that are composed only of lignin preparations. Lignin-based materials would be much weaker mechanically if interstices remain in significant numbers between adjoining macromolecular structures that consist of rigid crosslinked chains. In 1982, random-coil features in the hydrodynamic character of kraft lignin (KL) components were evident from ultracentrifugal sedimentation equilibrium studies of their SEC behavior. In 1997, it was recognized that the macromolecular species in plastics with 85 wt% levels of KL are associated complexes rather than individual components. Finally, in 2016, the first polymeric material composed entirely of ball-milled softwood lignin (BML) was found to support a tensile strength above polyethylene. Except in its molecular weight, the BML was similar in structure to the native biopolymer. It was composed of associated lignin complexes, each with aromatic rings arranged in two domains. The inner domain maintains structural integrity largely through noncovalent interactions between cofacially-offset aromatic rings; the peripheral domain contains a higher proportion of edge-on aromatic-ring arrangements. Interdigitation between peripheral domains in adjoining complexes creates material continuity during casting. By interacting at low concentrations with the peripheral domains, non-lignin blend components can improve the tensile strengths of BML-based plastics to values well beyond those seen in polystyrene. The KL-based plastics are weaker because the peripheral domains of adjoining complexes are less capable of interdigitation than those of BML. Blending with 5 wt% 1,8-dinitroanthraquinone results in a tensile strength above that of polyethylene. Analogous effects can be achieved with 10 wt% maple γ-valerolactone (GVL) lignin which, with a structure close to the native biopolymer, imparts some native character to the peripheral domains of the KL complexes. Comparable enhancements in the behavior of BML complexes upon blending with 10 wt% ball-milled corn-stover lignin (BMCSL) result in lignin-only polymeric materials with tensile strengths well beyond polystyrene.

Blend configuration in functional polymeric materials with a high lignin content.

Lignins upgrade the lignocellulosic cell-wall domains in all vascular plants; they embody 20-30% of terrestrial organic carbon. For 50 years, mistaken assumptions about the configuration of lignin have hindered the development of useful polymeric materials with a lignin content above 40 wt%. Now, polymeric materials composed only of methylated softwood lignin derivatives can exhibit better tensile behavior than polystyrene. Marked improvements may be achieved with small quantities (5-10 wt%) of miscible blend components as simple as poly(ethylene glycol). These observations contradict commonly held views about crosslinking or hyper-branching in lignin chains. The hydrodynamic compactness of the macromolecular lignin species arises from powerful noncovalent interactions between the lignin substructures. Individual lignin components undergo association to form macromolecular complexes that are preserved in plastics with a very high lignin content. Material continuity results from interpenetration between the peripheral components in adjoining lignin complexes. Through interactions with the peripheral domains, miscible blend components modulate the strength and ductility of these utterly original lignin-based plastics.

Comparison of the efficacy and safety of URSL, RPLU, and MPCNL for treatment of large upper impacted ureteral stones: a randomized controlled trial.

BACKGROUND: There are three minimally invasive methods for the management of large upper impacted ureteral stones: mini-percutaneous nephrolithotomy (MPCNL), transurethral ureteroscope lithotripsy (URSL), and retroperitoneal laparoscopic ureterolithotomy (RPLU). This study aimed to compare MPCNL, URSL, and RPLU, and to evaluate which one is the best choice for large upper impacted ureteral stones. METHODS: Between January 2012 and December 2015, at the Department of Urology, Huai'an First People's Hospital, 150 consecutively enrolled patients with a large upper impacted ureteral stone (>15 mm) were included. The patients were randomly divided (1:1:1) into the MPCNL, URSL, and RPLU groups. The primary endpoint was success of stone removal measured 1 month postoperatively and the secondary endpoints were intraoperative and postoperative parameters and complications. RESULTS: Fifteen patients needed auxiliary ESWL after URSL, and 3 patients after MPCNL, but none after RPLU. The stone clearance rate was 96% (48/50) in the MPCNL group and 72% (33/46) in the URSL group. In the RPLU group the stones were completely removed and the stone clearance rate was 100% (48/48) (P = 0.021 vs. URSL; P = 0.083 vs. MPCNL). Operation-related complications were similar among the three groups (all P > 0.05). Hospital stay was shorter in the URSL group compared with MPCNL (P = 0.003). Operation time was the shortest with URSL and the longest with MPCNL (all P < 0.05). CONCLUSIONS: MPCNL and RPUL are more suitable for upper ureteral impacted stones of >15 mm. URSL could be considered if the patient is not suitable for general anesthesia, or the patient requests transurethral uretroscopic surgery. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR-INR-17011507 ; Registration date: 2017-5-22).

LINC00312 inhibits the migration and invasion of bladder cancer cells by targeting miR-197-3p.

To investigate the influence of the long non-coding RNA LINC00312 on bladder cancer (BC) cell invasion and metastasis by targeting miR-197-3p. BC and corresponding adjacent tissues were collected. LINC00312 and miR-197-3p were measured, and their correlation was detected through quantitative real-time PCR (qRT-PCR). BC cell line T24 was transfected and grouped (five groups) according to different transfection conditions. A scratch test was applied to analyze cell migration, and a Transwell assay was used to test cell invasion ability. Western blotting was to measure matrix metalloproteinase (MMP)-2, MMP-9, and the tissue inhibitor of metalloproteinase 2 (TIMP2) protein levels. qRT-PCR indicated that LINC00312 expression was lower but miR-197-3p expression was higher in BC tissues compared with adjacent tissues; LINC00312 was negatively correlated with miR-197-3p. The migration test revealed that the downregulation of miR-197-3p and overexpression of LINC00312 inhibited cell migration and invasion abilities, while the overexpression of miR-197-3p and the upregulation of LINC00312 promoted cell migration and invasion. BC cells with downregulated miR-197-3p or upregulated LINC00312 had low MMP-2 and MMP-9 levels but high TIMP2. LINC00312 inhibited BC cell invasion and metastasis through mediating miR-197-3p.

Upregulation of microRNA-96 and its oncogenic functions by targeting CDKN1A in bladder cancer.

BACKGROUND: Genome-wide miRNA expression profile has identified microRNA (miR)-96 as one of upregulated miRNAs in clinical bladder cancer (BC) tissues compared to normal bladder tissues. The aim of this study was to confirm the expression pattern of miR-96 in BC tissues and to investigate its involvement in carcinogenesis. METHODS: Quantitative real-time PCR was performed to detect the expression levels of miR-96 in 60 BC and 40 normal control tissues. Bioinformatics prediction combined with luciferase reporter assay were used to verify whether the cyclin-dependent kinase inhibitor CDKN1A was a potential target gene of miR-96. Cell counting kit-8 and apoptosis assays were further performed to evaluate the effects of miR-96-CDKN1A axis on cell proliferation and apoptosis of BC cell lines. RESULTS: We validated that miR-96 was significantly increased in both human BC tissues and cell lines. According to the data of miRTarBase, CDKN1A might be a candidate target gene of miR-96. In addition, luciferase reporter and Western blot assays respectively demonstrated that miR-96 could bind to the putative seed region in CDKN1A mRNA 3'UTR, and significantly reduce the expression level of CDKN1A protein. Moreover, we found that the inhibition of miR-96 expression remarkably decreased cell proliferation and promoted cell apoptosis of BC cell lines, which was consistent with the findings observed following the introduction of CDKN1A cDNA without 3'UTR restored miR-96. CONCLUSIONS: Our data reveal that miR-96 may function as an onco-miRNA in BC. Upregulation of miR-96 may contribute to aggressive malignancy partly through suppressing CDKN1A protein expression in BC cells.

Neural representation of probabilities for Bayesian inference.

Bayesian models are often successful in describing perception and behavior, but the neural representation of probabilities remains in question. There are several distinct proposals for the neural representation of probabilities, but they have not been directly compared in an example system. Here we consider three models: a non-uniform population code where the stimulus-driven activity and distribution of preferred stimuli in the population represent a likelihood function and a prior, respectively; the sampling hypothesis which proposes that the stimulus-driven activity over time represents a posterior probability and that the spontaneous activity represents a prior; and the class of models which propose that a population of neurons represents a posterior probability in a distributed code. It has been shown that the non-uniform population code model matches the representation of auditory space generated in the owl's external nucleus of the inferior colliculus (ICx). However, the alternative models have not been tested, nor have the three models been directly compared in any system. Here we tested the three models in the owl's ICx. We found that spontaneous firing rate and the average stimulus-driven response of these neurons were not consistent with predictions of the sampling hypothesis. We also found that neural activity in ICx under varying levels of sensory noise did not reflect a posterior probability. On the other hand, the responses of ICx neurons were consistent with the non-uniform population code model. We further show that Bayesian inference can be implemented in the non-uniform population code model using one spike per neuron when the population is large and is thus able to support the rapid inference that is necessary for sound localization.

Direction selectivity mediated by adaptation in the owl's inferior colliculus.

Motion direction is a crucial cue for predicting future states in natural scenes. In the auditory system, the mechanisms that confer direction selectivity to neurons are not well understood. Neither is it known whether sound motion is encoded independently of stationary sound location. Here we investigated these questions in neurons of the owl's external nucleus of the inferior colliculus, where auditory space is represented in a map. Using a high-density speaker array, we show that the preferred direction and the degree of direction selectivity can be predicted by response adaptation to sounds moving over asymmetric spatial receptive fields. At the population level, we found that preference for sounds moving toward frontal space increased with eccentricity in spatial tuning. This distribution was consistent with larger receptive-field asymmetry in neurons tuned to more peripheral auditory space. A model of suppression based on spatiotemporal summation predicted the observations. Thus, response adaptation and receptive-field shape can explain direction selectivity to acoustic motion and an orderly distribution of preferred direction.

The application of micro-vacuo-certo-contacting ophthalmophanto in X-ray radiosurgery for tumors in an eyeball.

The large errors of routine localization for eyeball tumors restricted X-ray radiosurgery application, just for the eyeball to turn around. To localize the accuracy site, the micro-vacuo-certo-contacting ophthalmophanto (MVCCOP) method was used. Also, the outcome of patients with tumors in the eyeball was evaluated. In this study, computed tomography (CT) localization accuracy was measured by repeating CT scan using MVCCOP to fix the eyeball in radiosurgery. This study evaluated the outcome of the tumors and the survival of the patients by follow-up. The results indicated that the accuracy of CT localization of Brown-Roberts-Wells (BRW) head ring was 0.65 mm and maximum error was 1.09 mm. The accuracy of target localization of tumors in the eyeball using MVCCOP was 0.87 mm averagely, and the maximum error was 1.19 mm. The errors of fixation of the eyeball were 0.84 mm averagely and 1.17 mm maximally. The total accuracy was 1.34 mm, and 95% confidence accuracy was 2.09 mm. The clinical application of this method in 14 tumor patients showed satisfactory results, and all of the tumors showed the clear rims. The site of ten retinoblastomas was decreased significantly. The local control interval of tumors were 6 ∼ 24 months, median of 10.5 months. The survival of ten patients was 7 ∼ 30 months, median of 16.5 months. Also, the tumors were kept stable or shrank in the other four patients with angioma and melanoma. In conclusion, the MVCCOP is suitable and dependable for X-ray radiosurgery for eyeball tumors. The tumor control and survival of patients are satisfactory, and this method can effectively postpone or avoid extirpation of eyeball.

MiR-7-5p is frequently downregulated in glioblastoma microvasculature and inhibits vascular endothelial cell proliferation by targeting RAF1.

The aberrant expression of microRNAs (miRNAs) is always associated with tumor development and progression. Microvascular proliferation is one of the unique pathologic features of glioblastoma (GBM) . In this study, the microvasculature from GBM or normal brain tissue derived from neurosurgeries was purified and total RNA was isolated from purified microvasculature. The difference of miRNA expression profiles between glioblastoma microvasculature and normal brain capillaries was investigated. It was found that miR-7-5p in GBM microvessels was significantly reduced compared with that in normal brain capillaries. In the in vitro experiments, overexpression of miR-7-5p significantly inhibited human umbilical vein endothelial cell proliferation. Forced expression of miR-7-5p in human umbilical vein endothelial cells in vitro significantly reduced the protein level of RAF1 and repressed the activity of the luciferase, a reporter vector carrying the 3'-untranslated region of RAF1. These findings indicate that RAF1 is one of the miR-7-5p target genes. Furthermore, a significant inverse correlation between miR-7-5p expression and RAF1 protein level in GBM microvasculature was found. These data suggest that miR-7-5p functions as a tumor suppressor gene to regulate GBM microvascular endothelial cell proliferation potentially by targeting the RAF1 oncogene, implicating an important role for miR-7-5p in the pathogenesis of GBM. It may serve as a guide for the antitumor angiogenesis drug development.

Supratentorial cortical ependymoma: case series and review of the literature.

Supratentorial cortical ependymoma (CE), a rare type of ependymoma, is located in the superficial cortex. We reported 11 patients (six female and five male) with CE. The age of the patients ranged from 2 to 63 years old with a median age of 47 years at the time of diagnosis. On MRI, enhancement was noted in all cases with solid appearance in six cases, and solid and cystic appearance in five cases. The frontal and parietal regions were the most common locations for CE. On histology, two were low-grade (WHO grade II) and nine were WHO grade III anaplastic ependymomas. Some tumors exhibited clear cell, spindle (tanycytic) and giant cell morphologies, as well as the classic ependymoma morphology. Dura-based tumor nodules and even tumor dissemination along the dura can be seen in CEs. Low grade CEs have a higher likelihood to present with seizures, a lower likelihood to cause brain edema, tumor recurrence and lower mortality than anaplastic ependymomas. While difficult, anaplastic CEs may be distinguished from glioblastoma by a clear interface between tumor and adjacent brain tissue, relative uniformity of tumor cell nuclei and immunopositivity for epithelial membrane antigen and/or CD99. As is the case for ependymomas in general, gross total resection is still the treatment of choice for CEs.

Analysis of factors affecting intraoperative hemorrhage during percutaneous nephrolithotomy and establishment of nomogram model.

Intraoperative hemorrhage is an important factor affecting intraoperative safety and postoperative patient recovery in percutaneous nephrolithotomy (PCNL). This study aimed to identify the factors that influence intraoperative hemorrhage during PCNL and develop a predictive nomogram model based on these factors.A total of 118 patients who underwent PCNL at the Department of Urology, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University from January 2021 to September 2023 was included in this study. The patients were divided into a hemorrhage group (58 cases) and a control group (60 cases) based on the decrease in hemoglobin levels after surgery. The clinical data of all patients were collected, and both univariate analysis and multivariate logistic regression analysis were conducted to identify the independent risk factors for intraoperative hemorrhage during PCNL. The independent risk factors were used to construct a nomogram model using R software. Additionally, receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA) were utilized to evaluate the model.Multivariate logistic regression analysis revealed that diabetes, long operation time and low psoas muscle mass index (PMI) were independent risk factors for intraoperative hemorrhage during PCNL (P < 0.05). A nomogram model was developed incorporating these factors, and the areas under the ROC curve (AUCs) in the training set and validation set were 0.740 (95% CI: 0.637-0.843) and 0.742 (95% CI: 0.554-0.931), respectively. The calibration curve and Hosmer-Lemeshow test (P = 0.719) of the model proved that the model was well fitted and calibrated. The results of the DCA showed that the model had high value for clinical application.Diabetes, long operation time and low PMI were found to be independent risk factors for intraoperative hemorrhage during PCNL. The nomogram model based on these factors can be used to predict the risk of intraoperative hemorrhage, which is beneficial for perioperative intervention in high-risk groups to improve the safety of surgery and reduce the incidence of postoperative complications.

Identification and validation of the biomarkers related to ferroptosis in calcium oxalate nephrolithiasis.

Ferroptosis is a specific type of programmed cell death characterized by iron-dependent lipid peroxidation. Understanding the involvement of ferroptosis in calcium oxalate (CaOx) stone formation may reveal potential targets for this condition. The publicly available dataset GSE73680 was used to identify 61 differentially expressed ferroptosis-related genes (DEFERGs) between normal kidney tissues and Randall's plaques (RPs) from patients with nephrolithiasis through employing weighted gene co-expression network analysis (WGCNA). The findings were validated through in vitro and in vivo experiments using CaOx nephrolithiasis rat models induced by 1% ethylene glycol administration and HK-2 cell models treated with 1 mM oxalate. Through WGCNA and the machine learning algorithm, we identified LAMP2 and MDM4 as the hub DEFERGs. Subsequently, nephrolithiasis samples were classified into cluster 1 and cluster 2 based on the expression of the hub DEFERGs. Validation experiments demonstrated decreased expression of LAMP2 and MDM4 in CaOx nephrolithiasis animal models and cells. Treatment with ferrostatin-1 (Fer-1), a ferroptosis inhibitor, partially reversed oxidative stress and lipid peroxidation in CaOx nephrolithiasis models. Moreover, Fer-1 also reversed the expression changes of LAMP2 and MDM4 in CaOx nephrolithiasis models. Our findings suggest that ferroptosis may be involved in the formation of CaOx kidney stones through the regulation of LAMP2 and MDM4.

Characterization of the microplastic photoaging under the action of typical salt ions of biological nitrogen removal processes.

Microplastics (MPs) are one of the most prevalent and diverse contaminants, and wastewater treatment plants are significant MP aggregators. Controlling the pollution caused by microplastics requires an understanding of how they age. The properties of the MPs photoaging process under the influence of salt ions typical of biological nitrogen elimination processes were disclosed in this work. The aging process of polyvinyl chloride microplastics (PVC-MPs) was greatly slowed down by greater HCO3- and NO2- concentrations, according to a comparison of the carbonyl index changes that occurred during photoaging. The carbonyl index had a negative correlation with the thermal stability of the photo-aged PVC-MPs, and aging accelerated the elimination of chlorine from the water. The samples were aged by UV radiation after 36 h at 40 °C, and the amount of chlorine eliminated was 10.13 times greater than that of the original MPs samples. It was discovered that the leachate concentration of aged MPs dramatically increased with decreasing particle size and was positively connected with the level of aging by comparing the concentration of leachate for two particle sizes (1 mm and 100 m). Photoaging caused MPs to become rougher, which in turn improved the NO3--N, NH4+-N, and NO2--N adsorption by PVC-MPs.

ZCHSound: Open-Source ZJU Paediatric Heart Sound Database With Congenital Heart Disease.

BACKGROUND: Congenital heart disease (CHD) is a common birth defect in children. Intelligent auscultation algorithms have been proven to reduce the subjectivity of diagnoses and alleviate the workload of doctors. However, the development of this algorithm has been limited by the lack of reliable, standardized, and publicly available pediatric heart sound databases. Therefore, the objective of this research is to develop a large-scale, high-standard, high-quality, and accurately labeled pediatric congenital heart disease (CHD) heart sound database, and perform classification tasks to evaluate its performance, filling this important research gap. METHOD: From 2020 to 2022, we collaborated with experienced cardiac surgeons from Zhejiang University Children's Hospital to collect heart sound signals from 1259 participants using electronic stethoscopes. To ensure accurate disease diagnosis, the cardiac ultrasound images for each participant were acquired by an experienced ultrasonographer, and the final diagnosis was confirmed through the consensus of two cardiac experts or cardiac surgeons. To establish the benchmark of ZCHSound, we extracted 84 time-frequency features from the heart sounds and evaluated the performance of the classification task using machine learning models. Additionally, we evaluated the importance scores of the 84 features in distinguishing between normal and pathological heart sounds in children using SHapley Additive exPlanations (SHAP) values. RESULTS: The ZCHSound database contains heart sound data from 1259 participants, with all data divided into two datasets: one is a high-quality, filtered clean heart sound dataset, and the other is a low-quality, noisy heart sound dataset. In the evaluation of the high-quality dataset, our random forest ensemble model achieved an F1 score of 90.3% in the classification task of normal and pathological heart sounds. Moreover, the SHAP analysis results demonstrate that frequency-domain features have a more significant impact on the model output compared to time-domain features. Features related to the cardiac diastolic period have a greater influence on the model's classification results compared to those related to the systolic period. CONCLUSION: This study has successfully established a large-scale, high-quality, rigorously standardized pediatric CHD sound database with precise disease diagnosis. This database not only provides important learning resources for clinical doctors in auscultation knowledge but also offers valuable data support for algorithm engineers in developing intelligent auscultation algorithms. Our data can be accessed and downloaded by the public at http://zchsound.ncrcch.org.cn/.

Single-Cell Transcriptome Analysis Identified Core Genes and Transcription Factors in Mesenchymal Cell Differentiation during Liver Cirrhosis.

BACKGROUND: Mesenchymal cells, including hepatic stellate cells (HSCs), fibroblasts (FBs), myofibroblasts (MFBs), and vascular smooth muscle cells (VSMCs), are the main cells that affect liver fibrosis and play crucial roles in maintaining tissue homeostasis. The dynamic evolution of mesenchymal cells is very important but remains to be explored for researching the reversible mechanism of hepatic fibrosis and its evolution mechanism of hepatic fibrosis to cirrhosis. METHODS: Here, we analysed the transcriptomes of more than 50,000 human single cells from three cirrhotic and three healthy liver tissue samples and the mouse hepatic mesenchymal cells of two healthy and two fibrotic livers to reconstruct the evolutionary trajectory of hepatic mesenchymal cells from a healthy to a cirrhotic state, and a subsequent integrative analysis of bulk RNA sequencing (RNA-seq) data of HSCs from quiescent to active (using transforming growth factor ß1 (TGF-ß1) to stimulate LX-2) to inactive states. RESULTS: We identified core genes and transcription factors (TFs) involved in mesenchymal cell differentiation. In healthy human and mouse livers, the expression of NR1H4 and members of the ZEB families (ZEB1 and ZEB2) changed significantly with the differentiation of FB into HSC and VSMC. In cirrhotic human livers, VSMCs transformed into HSCs with downregulation of MYH11, ACTA2, and JUNB and upregulation of PDGFRB, RGS5, IGFBP5, CD36, A2M, SOX5, and MEF2C. Following HSCs differentiation into MFBs with the upregulation of COL1A1, TIMP1, and NR1H4, a small number of MFBs reverted to inactivated HSCs (iHSCs). The differentiation trajectory of mouse hepatic mesenchymal cells was similar to that in humans; however, the evolution trajectory and proportion of cell subpopulations that reverted from MFBs to iHSCs suggest that the mouse model may not accurately reflect disease progression and outcome in humans. CONCLUSIONS: Our analysis elucidates primary genes and TFs involved in mesenchymal cell differentiation during liver fibrosis using scRNA-seq data, and demonstrated the core genes and TFs in process of HSC activation to MFB and MFB reversal to iHSC using bulk RNA-seq data of human fibrosis induced by TGF-ß1. Furthermore, our findings suggest promising targets for the treatment of liver fibrosis and provide valuable insights into the molecular mechanisms underlying its onset and progression.

Pipeline Embolization Device for intracranial aneurysms presenting with mass effect: a large Chinese cohort.

BACKGROUND: Unruptured intracranial aneurysm treatment aims to reduce the risk of aneurysm rupture and bleeding, relieves symptoms and improve the quality of life for patients. This study aimed to assess the safety and efficacy of Pipeline Embolization Device (PED, Covidien/Medtronic, Irvine, CA) treatment for intracranial aneurysms presenting with mass effect in real-world settings. METHODS: We selected patients from the PED in China Post-Market Multi-Center Registry Study with mass effect presentation. The study endpoints included postoperative mass effect deterioration and mass effect relief at follow-up (3-36 months). We conducted multivariate analysis to identify factors associated with mass effect relief. Subgroup analyses by aneurysm location, size and form were also performed. RESULTS: This study included 218 patients with a mean age of 54.3±11.8 years and a female predominance of 74.0% (162/218). The postoperative mass effect deterioration rate was 9.6% (21/218). During a median follow-up period of 8.4 months, the mass effect relief rate was 71.6% (156/218). Notably, immediate aneurysm occlusion following treatment was significantly associated with mass effect relief (OR 0.392, 95% CI, 0.170 to 0.907, p=0.029). Subgroup analysis demonstrated that adjunctive coiling contributed to mass effect relief in cavernous aneurysms, while dense embolism impeded symptom relief in aneurysms<10 mm and saccular aneurysms. CONCLUSIONS: Our data confirmed the efficacy of PED in relieving mass effect. The findings of this study provide support for endovascular treatment to alleviate mass effect in unruptured intracranial aneurysms. TRIAL REGISTRATION NUMBER: NCT03831672.

Population-wide bias of surround suppression in auditory spatial receptive fields of the owl's midbrain.

The physical arrangement of receptive fields (RFs) within neural structures is important for local computations. Nonuniform distribution of tuning within populations of neurons can influence emergent tuning properties, causing bias in local processing. This issue was studied in the auditory system of barn owls. The owl's external nucleus of the inferior colliculus (ICx) contains a map of auditory space in which the frontal region is overrepresented. We measured spatiotemporal RFs of ICx neurons using spatial white noise. We found a population-wide bias in surround suppression such that suppression from frontal space was stronger. This asymmetry increased with laterality in spatial tuning. The bias could be explained by a model of lateral inhibition based on the overrepresentation of frontal space observed in ICx. The model predicted trends in surround suppression across ICx that matched the data. Thus, the uneven distribution of spatial tuning within the map could explain the topography of time-dependent tuning properties. This mechanism may have significant implications for the analysis of natural scenes by sensory systems.