Deep learning based retinal vessel segmentation and hypertensive retinopathy quantification using heterogeneous features cross-attention neural network.

Retinal vessels play a pivotal role as biomarkers in the detection of retinal diseases, including hypertensive retinopathy. The manual identification of these retinal vessels is both resource-intensive and time-consuming. The fidelity of vessel segmentation in automated methods directly depends on the fundus images' quality. In instances of sub-optimal image quality, applying deep learning-based methodologies emerges as a more effective approach for precise segmentation. We propose a heterogeneous neural network combining the benefit of local semantic information extraction of convolutional neural network and long-range spatial features mining of transformer network structures. Such cross-attention network structure boosts the model's ability to tackle vessel structures in the retinal images. Experiments on four publicly available datasets demonstrate our model's superior performance on vessel segmentation and the big potential of hypertensive retinopathy quantification.

Eosinophil peroxidase promotes bronchial epithelial cells to secrete asthma-related factors and induces the early stage of airway remodeling.

Asthma is a heterogeneous disease characterized by chronic airway inflammation, reversible airflow limitation, and airway remodeling. Eosinophil peroxidase (EPX) is the most abundant secondary granule protein unique to activated eosinophils. In this study, we aimed to illustrate the effect of EPX on the epithelial-mesenchymal transition (EMT) in BEAS-2B cells. Our research found that both EPX and ADAM33 were negatively correlated with FEV1/FVC and FEV1%pred, and positively correlated with IL-5 levels. Asthma patients had relatively higher levels of ADAM33 and EPX compared to the healthy control group. The expression of TSLP, TGF-ß1 and ADAM33 in the EPX intervention group was significantly higher. Moreover, EPX could promote the proliferation, migration and EMT of BEAS-2B cells, and the effect of EPX on various factors was significantly improved by the PI3K inhibitor LY294002. The findings from this study could potentially offer a novel therapeutic target for addressing airway remodeling in bronchial asthma, particularly focusing on EMT.

Predictive value of serum lncRNA MALAT1 for the recurrence of persistent atrial fibrillation after radiofrequency ablation.

Objective: The authors investigated the predictive value of MALAT1 for persistent atrial fibrillation (PAF) recurrence after radiofrequency ablation. Methods: Serum MALAT1 level was determined. The correlation between MALAT1 and high-sensitivity C-reactive protein/left atrial diameter (LAD) was analyzed. The predictive value of MALAT1 was evaluated. The postoperative recurrence rate in patients with high/low MALAT1 was compared. Independent risk factors for postoperative recurrence were analyzed. Results: MALAT1 was elevated in PAF patients and positively correlated with high-sensitivity C-reactive protein/LAD. MALAT1/high-sensitivity C-reactive protein/LAD were enhanced in patients with recurrent PAF. Patients with high MALAT1 had a higher recurrence rate. Upregulated MALAT1 was an independent risk factor for postoperative PAF recurrence. Conclusion: Serum MALAT1 level >2.03 predicts postoperative recurrence of PAF, and PAF patients with high MALAT1 have a higher risk of postoperative recurrence.

Atrial fibrillation (AF) is a common cardiac arrhythmia (abnormal heartbeat), which usually manifests as an irregular and rapid rhythm. In severe cases, AF can lead to cardiovascular diseases such as thromboembolism (narrowing and blockage of blood vessels) and heart failure (impaired pumping function of the heart). Cardiac radiofrequency ablation is a common method used to treat AF. However, patients with PAF still have a high rate of late recurrence after the operation, so there is an urgent need to identify suitable biochemical markers for predicting the postoperative recurrence of PAF. lncRNAs are a type of noncoding nucleic acid; they do not encode proteins, have various biological functions and are widely distributed in living organisms. The lncRNA MALAT1 has been considered a potential therapeutic target and biomarker in several cardiovascular diseases. This study demonstrated that the serum level of MALAT1 in PAF patients was significantly higher than that in normal subjects and MALAT1 level was elevated in patients with recurrent PAF compared with patients without recurrence. The authors also found that serum MALAT1 could predict whether PAF will recur after operation, with a high accuracy. In addition, PAF patients with high expression of serum MALAT1 had a higher risk of postoperative recurrence. In summary, serum level of lncRNA MALAT1 can help predict postoperative recurrence of PAF and a high level of MALAT1 is indicative of a higher risk of postoperative recurrence. Analysis of serum lncRNA MALAT1 level in PAF patients before surgery can predict postoperative recurrence, and intervention programs that lower the MALAT1 level can be implemented to reduce the risk of postoperative recurrence of PAF and increase the success rate of the operation. This study has important implications for reducing the recurrence rate after radiofrequency ablation in PAF patients.

Relationship between left atrial appendage peak flow velocity and nonvalvular atrial fibrillation recurrence after cryoablation.

Background: Previous studies revealed the connection between left atrial appendage peak flow velocity (LAA-PEV) and postoperative persistent atrial fibrillation (AF) recurrence. Yet, this association is not necessarily generalizable to persistent AF patients undergoing initial cryoballoon ablation due to current gaps in the literature. Methods: We prospectively studied 74 consecutive individuals with persistent atrial fibrillation undergoing a cryoballoon ablation for the first time between January 2018 and January 2020. Before ablation, LAA-PEV was documented by transesophageal echocardiography (TEE). Subsequently, demographic information and other clinical characteristics of these participants were collected. A 96-h continuous cardiac monitor was reviewed regularly for recurrence of atrial fibrillation. Cox proportional hazards regression was used to investigate LAA-PEV as well as other clinical characteristics as a predictor of AF recurrence. Results: Our study found that AF recurrences had lower LAA-PEV than those without AF recurrence. A nonlinear relationship between the LAA-PEV and AF recurrence was observed in this study, which had an inflection point of 34.9. Subgroup analysis of female participants showed that LAA-PEV had a positive correlation with AF recurrence [ß = 0.8, 95% CI (0.7, 0.9), p < 0.05]. Conclusion: A low LAA-PEV is related to recurrence of atrial fibrillation and may predict AF recurrence after initial cryoballoon ablation for persistent atrial fibrillation. This finding may help improve treatment and care strategies for patients with persistent atrial fibrillation.

Single-cell analysis of peripheral blood from high-altitude pulmonary hypertension patients identifies a distinct monocyte phenotype.

Immune and inflammatory responses have an important function in the pathophysiology of pulmonary hypertension (PH). However, little is known about the immune landscape in peripheral circulation in patients with high-altitude pulmonary hypertension (HAPH). We apply single-cell transcriptomics to characterize the monocytes that are significantly enriched in the peripheral blood mononuclear cells (PBMC) of HAPH patients. We discover an increase in C1 (non-classical) and C2 (intermediate) monocytes in PBMCs and a decrease in hypoxia-inducible transcription factor-1α (HIF-1α) in all monocyte subsets associated with HAPH. In addition, we demonstrate that similar immune adaptations may exist in HAPH and PH. Overall, we characterize an immune cell atlas of the peripheral blood in HAPH patients. Our data provide evidence that specific monocyte subsets and HIF-1α downregulation might be implicated in the pathogenesis of HAPH.

Protective activity of Malus doumeri leaf extract on H2O2-induced oxidative injury in H9C2 rat cardiomyocytes.

In this study, Malus doumeri leaf extract (MDLE) was used to test its anti-oxidation capacity in vitro, it has been preliminarily analyzed for H2O2-induced oxidative damage in H9C2 cells and its main active components. The antioxidant capacity through DPPH (1, 1-Diphenyl-2-Picrylhydrazyl), ABTS+• [2,2,2'-azino-BIS-(3-ethylbenzo-thiazoline-6-sulfonic acid)] radical ion, •OH (hydroxyl radical), and • O 2 - (superoxide anion) were determined in vitro. The proliferation of H9C2 cells was examined by MTT [3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-Tetrazolium bromide]. MDA (malondialdehyde), SOD (superoxide dismutase), CAT (catalase), GSH (glutathione), and GSH-Px (glutathione peroxidase) were determined by colorimetry. Apoptosis induced by oxidative damage was detected by flow cytometry. The mRNA expression of antioxidant related genes of SOD, CAT, GSH, and GSH-Px were checked by qRT-PCR (quantitative real-time polymerase chain reaction). The MDLE main active components were analyzed by HPLC (high-performance liquid chromatography). MDLE had significant scavenging effects on DPPH, ABTS+•, •OH, and superoxide anion radicals in a concentration-dependent manner. H2O2 treatment could significantly lead to oxidative stress injury of H9C2 cells, and MDLE treatment significantly improved the degree of H9C2 cell damage, and showed a positive correlation with concentration. MDLE can also reduce apoptosis caused by oxidative damage. MDLE treatment could significantly reduce MDA content and increase CAT, SOD, GSH, and GSH-Px contents and expression. In addition, by HPLC analysis, the following six bioactive components were detected from MDLE: chlorogenic acid, isoquercitrin, quercetin, baicalin, and phloretin. Therefore, MDLE has a good protective effect on myocardial cells.

Estrogen inhibits vascular calcification in rats via hypoxia-induced factor-1α signaling.

OBJECTIVE: Calcification serves as a surrogate for atherosclerosis-associated vascular diseases, and coronary artery calcification is mediated by multiple pathogenic factors. Estrogen is a known factor that protects the arterial wall against atherosclerosis, but its role in the coronary artery calcification development remains largely unclear. This study tested the hypothesis that estrogen inhibits coronary artery calcification via the hypoxia-induced factor-1α pathway. METHODS: Eight-week-old healthy female Sprague-Dawley rats were castrated, and vitamin D3 was administered orally to establish. Hypoxia-induced factor-1 inhibitor was administered to test its effect on vascular calcification and expression of bone morphogenetic protein 2 and runt-related transcription factor-2. Vascular smooth muscle cell calcification was induced with CaCl2 in rat aortic smooth muscle cells in the presence or absence of E2(17ß-estradiol) and bone morphogenetic protein 2 siRNA intervention. RESULTS: The estrogen levels in ovariectomized rats were significantly decreased, as determined by ELISA. Expression of hypoxia-induced factor-1α mRNA and protein was significantly increased in vascular cells with calcification as compared to those without calcification (p < 0.01). E2 treatment decreased the calcium concentration in vascular cell calcification and cell calcium nodules in vitro (p < 0.05). E2 also lowered the levels of hypoxia-induced factor-1α mRNA and protein (p < 0.01). Oral administration of the hypoxia-induced factor-1α inhibitor dimethyloxetane in castrated rats alleviated vascular calcification and expression of osteogenesis-related transcription factors, bone morphogenetic protein 2 and RUNX2 (p < 0.01). Finally, bone morphogenetic protein 2 siRNA treatment decreased the levels of p-Smad1/5/8 in A7r5 calcification cells (p < 0.01). CONCLUSION: Estrogen deficiency enhances vascular calcification. Treatment with estrogen reduces the expression of hypoxia-induced factor-1α as well as vascular calcification in rats. The estrogen effects occur in a fashion dependent on hypoxia-induced factor-1α regulation of bone morphogenetic protein-2 and downstream Smad1/5/8.

Association of GWAS-supported noncoding area loci rs404860, rs3117098, and rs7775228 with asthma in Chinese Zhuang population.

BACKGROUND: Asthma is a complicated and polygenic inheritance disease, and its prevalence increases worldwide. Recent genome-wide association studies (GWASs) identified a significant association of single nucleotide polymorphism with asthma in the Japanese population. This study aimed to examine the association of GWAS-supported noncoding area loci, namely rs404860, rs3117098, and rs7775228, with asthma in Chinese Zhuang population. METHODS: A case-control study involving 223 individuals, comprising 123 patients with asthma and 100 healthy controls, was conducted. Genotypes were determined by polymerase chain reaction (PCR)/ligase detection reaction assay. The association between gene polymorphisms and asthma risk was calculated by logistic regression analysis using different genetic models through comparisons of alleles (A vs a), homozygote genotypes (AA vs aa), heterozygote genotypes (Aa vs aa), dominant models (AA+Aa vs aa), and recessive models (AA vs. Aa+aa). RESULTS: The distribution of the genotype frequency of rs3117098 was statistically different between the case and control groups. For rs3117098, significant associations were observed through comparisons of alleles (OR: 1.832, 95% CI: 1.048-3.204, P = .034) and dominant models (OR: 2.065, 95% CI: 1.001-4.260, P = .050). The statistical analysis showed no significant difference for loci rs404860 and rs7775228 between patients with asthma and controls. CONCLUSION: rs3117098 may be the risk factor for asthma in Chinese Zhuang population.

Association of IL1RL1 rs3771180 and TSLP rs1837253 variants with asthma in the Guangxi Zhuang population in China.

OBJECTIVE: IL-1 receptor-like 1 (IL1RL1) and thymic stromal lymphopoietin (TSLP) play important roles in asthma in various ways. IL1RL1 rs3771180 and TSLP rs1837253 single nucleotide polymorphisms (SNPs) are associated with asthma in some European nationals but not in Zhuang people. Accordingly, this study aimed to determine the associations of IL1RL1 rs3771180 and TSLP rs1837253 with asthma in Zhuang people. METHODS: We performed a case-control study to observe the association between the two polymorphisms and asthma in a Guangxi Zhuang cohort consisting of 123 asthmatic patients and 100 healthy controls. These individuals were recruited from the Department of Respiration of the First Affiliated Hospital of Guangxi Medical University. Multiplex PCR assay was used to identify the genotype of rs3771180 and rs1837253. Data were analyzed with SPSS 22.0 and SHEsis. RESULTS: rs1837253 showed significant differences between asthmatic and control groups in allele comparison (OR = 2.15; 95% CI = 1.27-3.63; P = 0.004), as well as in the homozygote (OR = 4.83; 95% CI = 1.47-16.47; P = 0.012), heterozygote (OR = 2.69; 95% CI = 1.20-6.00; P = 0.016), and dominant (OR = 3.01; 95% CI = 1.39-6.52; P = 0.005) genetic models. However, the genotype frequencies of rs3771180 did not obviously differ. CONCLUSION: rs1837253 is associated with asthma susceptibility and may increase the risk of asthma in Zhuang people in Guangxi.

Pulse pressure correlates with coronary artery calcification and risk for coronary heart disease: a study of elderly individuals in the rural region of Southwest China.

AIM: This study aimed to define the relationship between pulse pressure (PP) and coronary artery calcification (CAC), a proven surrogate marker for coronary heart disease. PATIENTS AND METHODS: A total of 170 participants 50-70 years of age from 11 villages of Yunnan Province of China were enrolled randomly into this study. They were examined routinely for diastolic and systolic blood pressure, PP, and CAC. RESULTS: The average PP in the CAC-positive group was significantly higher than that in the CAC-negative group. In the positive CAC group, there were significantly positive correlations between PP and CAC score, volume, mass, as well as density. The area under the receiver operating characteristic curve analysis showed that PP performed well in predicting CAC. CONCLUSION: In conclusion, among the rural people of southwest of China, PP correlates positively with the coronary calcium Agatston score, volume, mass, and density. PP predicted CAC as well as Framingham Risk Score. The measurement of PP widening may serve as an alternative and convenient method for assessing CAC risk in rural populations with poor accessibility and economic disadvantage over coronary computed tomography scanning.

Impact of proteasome inhibitor MG-132 on expression of NF-κB, IL-1ß and histological remodeling after myocardial infarction.

The aim of the present study was to investigate the impact of carbobenzoxy-Leu-Leu-leucinal (MG-132) on myocardial remodeling in rats with myocardial infarction (MI) and investigate the possible underlying mechanisms. The rat model of MI was established, followed by administration of MG-132 (MG group), pyrrolidine dithiocarbamic acid (PDTC group) or normal saline (MI group) for 28 days. The expression of nuclear factor-κB (NF-κB) p65, interleukin 1ß (IL-1ß) and matrix metalloproteinase 2 (MMP-2), as well as the total volume of collagen and the ratio of type I/III collagen were then detected. Total collagen, including type I and III collagen, and the ratio of type I/III collagen were significantly increased in MI rats compared with those in the sham group (P<0.01), while it was significantly decreased in the PDTC and MG groups compared with that in the MI group (P<0.01). A similar trend was identified for the expression of NF-κB, IL-1ß and MMP-2, which was significantly increased in the MI group compared with that in the sham group (P<0.01), while it was significantly decreased in the MG and PDTC groups compared with that in the MI group (P<0.01). In conclusion, MG-132 was demonstrated to improve post-MI tissue remodeling, and the mechanism may be associated with the inhibition of NF-κB activation and the downregulation of inflammatory cytokines, such as IL-1ß.

Beta-2 adrenergic receptor (ADRB2) gene polymorphisms and the risk of asthma: a meta-analysis of case-control studies.

BACKGROUND AND OBJECTIVE: A number of studies have assessed the relationship between beta-2 adrenergic receptor (ADRB2) gene polymorphisms and asthma risk. However, the results are inconsistent. A meta-analysis that focused on the association between asthma and all ADRB2 polymorphisms with at least three case-control studies was thus performed. METHODS: A literature search of the PubMed, Embase, Web of Science, CNKI, and Wangfang databases was conducted. Odds ratios with 95% confidence intervals were used to assess the strength of associations. RESULTS: Arg16Gly, Gln27Glu, Thr164Ile, and Arg19Cys single nucleotide polymorphisms (SNPs) were identified in 46 case-control studies. The results showed that not all of the SNPs were associated with asthma in the overall population. Significant associations were found for the Arg16Gly polymorphism in the South American population via dominant model comparison (OR = 1.754, 95% CI = 1.179-2.609, I2 = 16.9%, studies  = 2, case  = 314, control  = 237) in an analysis stratified by ethnicity. For the Gln27Glu polymorphism, a protective association was found in children via recessive model comparison (OR = 0.566, 95% CI = 0.417-0.769, I2 = 0.0%, studies  = 11, case  = 1693, control  =  502) and homozygote genotype comparison (OR = 0.610, 95% CI = 0.434-0.856, I2 = 0.0%, studies  = 11, case  = 1693, control  = 1502), and in adults via dominant model comparison (OR = 0.864, 95% CI = 0.768-0.971, I2 = 46.9%, n = 18, case  = 3160, control  = 3433). CONCLUSIONS: None of the ADRB2 gene polymorphisms were reproducibly associated with a risk of asthma across ethnic groups in the general population.

Significant association between asthma risk and the GSTM1 and GSTT1 deletion polymorphisms: an updated meta-analysis of case-control studies.

Polymorphisms in GSTM1 and GSTT1 may be associated with asthma risk, yet several studies and meta-analyses have reported inconclusive results. Therefore, an updated meta-analysis was conducted. Literature searches were performed using the Pubmed, Embase and Web of Science databases until October 2012. Variant 'null' genotype was compared with wild-type 'present' in the pooled data. All statistical analyses were performed using STATA 11.0. A total of 26 case-control studies were suitable for inclusion in the meta-analysis. In the overall population, a significant association was found for both the GSTM1 (odds ratio (OR) = 1.452; 95% confidence interval (CI): 1.192-1.770) and GSTT1 polymorphism (OR = 1.792; 95% CI:1.293-2.483). For subgroup analysis by age, GSTM1 significantly increased risk for both children (OR = 1.368; 95% CI: 1.051-1.781) and adults (OR = 1.859; 95% CI: 1.183-2.921). For GSTT1, a significant association was only found in the adult population (OR = 2.312; 95%CI: 1.204-4.439). Based on subgroup analysis by ethnicity, a significant association for GSTM1 was found in Europe (OR = 1.303; 95% CI: 1.018-1.667), Africa (OR = 2.175; 95%CI: 1.560-3.031) and Latin America (OR = 2.265; 95%CI: 1.375-3.729). For GSTT1, significantly increased risk was found only for Asian (OR = 2.105; 95% CI: 1.101-4.025) and Russian (OR = 2.747; 95% CI: 1.071-7.046) populations. This meta-analysis provides evidence that GSTM1 and GSTT1 polymorphisms may be risk factors for asthma.

A disintegrin and metalloprotease 33 (ADAM33) gene polymorphisms and the risk of asthma: a meta-analysis.

Polymorphisms in the ADAM33 gene have been associated with asthma, but the data are controversial. Therefore, we reviewed the related studies and quantitatively summarized the associations between ADAM33 polymorphisms and asthma risk using meta-analysis. A dominant model (AA+Aa vs. aa), recessive model (AA vs. Aa+aa), additive model (AA vs. aa) and allelic model (A vs. a) were used to estimate the association between ADAM33 polymorphism and asthma risk. A total of 29 case-control studies referring to 14 SNPs were identified: rs2280091(T1), rs2787094(V4), rs528557(S2), rs2280090(T2), rs511898(F+1), rs44707(ST+4), rs3918396(S1), rs543749(V-1), rs574174(ST+7), rs597980(ST+5), rs2853209(S+1), rs2280089(T+1), rs612709(Q-1), and rs3746631(V5). The results indicated that S1, V-1, V5, S+1, S2, ST+4, ST+7, ST+5, and Q-1 were not associated with asthma. Significant associations were found with the T1, V4, F+1 and T+1 polymorphisms in the overall population. In the subgroup analysis by ethnicity, a positive result was only found for the T1, V4, F+1 and T2 polymorphisms in Asia but not in Europe or Latin America. This meta-analysis provides evidence that the T1, V4, F+1, T2, and T+1 polymorphisms in the ADAM33 gene are risk factors for asthma, especially in the Asian population.

Role of soil-derived dissolved substances in arsenic transport and transformation in laboratory experiments.

Dissolved substances derived from soil may interact with both soil surfaces and with arsenic and subsequently influence arsenic mobility and species transformation. The purpose of this study was to investigate arsenic transport and transformation in porous media with a specific focus on the impact of soil-derived dissolved substances, mainly consisting of inorganic colloids and dissolved organic matter (DOM), on these processes. Arsenic transport and transformation through columns, which were packed with uncoated sand (UC) or naturally coated sand (NC) and fed with arsenate (AsV) or monomethylarsonic acid (MMA) spiked influents, were investigated in the presence or absence of soil-derived dissolved substances. The presence of soil-derived inorganic colloids and/or DOM clearly enhanced As transport through the column, with the fraction of As leached out of column (referring to the total amount added) being increased from 23 to 46% (UC) and 21 to 50% (NC) in AsV experiments while 46 to 64% (UC) and 28 to 63% (NC) in MMA experiments. The association of arsenic with DOM and the competitive adsorption between arsenic and DOM could account for, at least partly, the enhanced As movement. Distinct species transformation of As during transport through soil columns was observed. When AsV was the initial species spiked in the influent solutions, only arsenite (AsIII) was detected in the effluents for UC columns; while both AsIII (dominant) and AsV were present for NC columns, with AsIII being the dominant species. When MMA was initially spiked in the influent solutions, all method detectable As species, AsIII, AsV, MMA, and dimethylarsenic acid (DMA) were present in the effluents for both soil columns. These results indicate that risk assessment associated with As contamination, particularly due to previous organoarsenical pesticide applications, should take into account the role of soil-derived dissolved substances in promoting As transport and As species transformation.

Interactions of arsenic and the dissolved substances derived from turf soils.

Monosodium methanearsonate (MSMA) is frequently used as an herbicide for the control of weeds in turf grasses at golf courses in Florida. There are concerns about arsenic (As) contamination of local shallow groundwater from the application of MSMA. The distinction between "free" As and colloid-bound/complexed As in soil solution is important for understanding the mobility and bioavailability of As in the environment. In this study, the equilibrium membrane (500 and 3500 Da) dialysis method was employed to determine the "free" and "bound" As in water extracts of five types of golf-course soils containing coated and uncoated sands in various proportions with peat. All samples were evaluated for arsenic species (arsenite, AsIII and arsenate, AsV), dissolved organic matter, and additional constituents (iron, aluminum, and calcium). The impacts of microbial growth were evaluated by conducting experiments with and without the addition of sodium azide for one particular soil type. Results indicate that (1) the presence of peat in the soils plays a significant role in the distribution of As in the dissolved phase of soil solutions; (2) the majority of As present in the soil extracts from soils containing peat was associated with substances of molecular weight (MW) between 500 and 3500 Da; (3) the association of As and dissolved organic matter (DOM) in the soil solution strongly affected As bioavailability, thus determining As transformations via microorganism-mediated processes; and (4) the presence of peat greatly enhanced the release of iron, aluminum, and calcium from soil. Amendment of sand with peat is a common practice at Florida golf courses. However, the addition of peat will alter the properties of the soils, which in turn could affect As transport and transformation. The results of this study are useful for understanding the factors controlling As trapping and transport within porous soil media and in developing comprehensive plans for managing and remediating As contaminated environments, such as golf courses.