Identification of potential therapeutic targets for plaque vulnerability based on an integrated analysis.

BACKGROUND AND AIMS: This study aimed to explore potential hub genes and pathways of plaque vulnerability and to investigate possible therapeutic targets for acute coronary syndrome (ACS). METHODS AND RESULTS: Four microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs), weighted gene coexpression networks (WGCNA) and immune cell infiltration analysis (IIA) were used to identify the genes for plaque vulnerability. Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Disease Ontology, Gene Ontology annotation and protein-protein interaction (PPI) network analyses were performed to explore the hub genes. Random forest and artificial neural networks were constructed for validation. Furthermore, the CMap and Herb databases were employed to explore possible therapeutic targets. A total of 168 DEGs with an adjusted P < 0.05 and approximately 1974 IIA genes were identified in GSE62646. Three modules were detected and associated with CAD-Class, including 891 genes that can be found in GSE90074. After removing duplicates, 114 hub genes were used for functional analysis. GO functions identified 157 items, and 6 pathways were enriched for the KEGG pathway at adjusted P < 0.05 (false discovery rate, FDR set at < 0.05). Random forest and artificial neural network models were built based on the GSE48060 and GSE34822 datasets, respectively, to validate the previous hub genes. Five genes (GZMA, GZMB, KLRB1, KLRD1 and TRPM6) were selected, and only two of them (GZMA and GZMB) were screened as therapeutic targets in the CMap and Herb databases. CONCLUSION: We performed a comprehensive analysis and validated GZMA and GZMB as a target for plaque vulnerability, which provides a therapeutic strategy for the prevention of ACS. However, whether it can be used as a predictor in blood samples requires further experimental verification.

Transcriptome and Hormonal Analysis of Agaricus bisporus Basidiome Response to Hypomyces perniciosus Infection.

Agaricus bisporus (Lange) Imbach is the most widely cultivated mushroom in the world. A. bisporus wet bubble disease is one of the most severe diseases of white button mushrooms and is caused by the fungal pathogen Hypomyces perniciosus. The pathogen causes a drastic reduction in mushroom yield because of malformation and deterioration of the basidiomes. However, the mechanism of the button mushroom's malformation development after infection with H. perniciosus remains obscure. Therefore, to reveal the mechanism of A. bisporus malformation caused by H. perniciosus, the interaction between the pathogen and host was investigated in this study using histopathological, physiological, and transcriptomic analyses. Results showed that irrespective of the growth stages of A. bisporus basidiomes infected with H. perniciosus, the host's malformed basidiomes and enlarged mycelia and basidia indicated that the earlier the infection with H. perniciosus, the more the malformation of the basidiomes. Analyzing physiological and transcriptomic results in tandem, we concluded that H. perniciosus causes malformation development of A. bisporus mainly by affecting the metabolism level of phytohormones (N6-isopentenyladenosine, cis-zeatin, and N6-[delta 2-isopentenyl]-adenine) of the host's fruiting bodies rather than using toxins. Our findings revealed the mechanism of the button mushroom's malformation development after infection with H. perniciosus, providing a reference for developing realistic approaches to control mushroom diseases. Our results further clarified the interaction between A. bisporus and H. perniciosus and identified the candidate genes for A. bisporus wet bubble disease resistance breeding. Additionally, our work provides a valuable theoretical basis and technical support for studying the interaction between other pathogenic fungi and their fungal hosts.

Identification of MYH6 as the potential gene for human ischaemic cardiomyopathy.

The present study aimed to explore the potential hub genes and pathways of ischaemic cardiomyopathy (ICM) and to investigate the possible associated mechanisms. Two microarray data sets (GSE5406 and GSE57338) were downloaded from the Gene Expression Omnibus (GEO) database. The limma package was used to analyse the differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Disease Ontology (DO) and Gene Ontology (GO) annotation analyses were performed. A protein-protein interaction (PPI) network was set up using Cytoscape software. Significant modules and hub genes were identified by the Molecular Complex Detection (MCODE) app. Then, further functional validation of hub genes in other microarrays and survival analysis were performed to judge the prognosis. A total of 1065 genes were matched, with an adjusted p < 0.05, and 17 were upregulated and 25 were downregulated with|log2 (fold change)|≥1.2. After removing the lengthy entries, GO identified 12 items, and 8 pathways were enriched at adjusted p < 0.05 (false discovery rate, FDR set at <0.05). Three modules with a score >8 after MCODE analysis and MYH6 were ultimately identified. When validated in GSE23561, MYH6 expression was lower in patients with CAD than in healthy controls (p < 0.05). GSE60993 data suggested that MYH6 expression was also lower in AMI patients (p < 0.05). In the GSE59867 data set, MYH6 expression was lower in CAD patients than in AMI patients and lower in heart failure (HF) patients than in non-HF patients. However, there was no difference at different periods within half a year, and HF was increased when MYH6 expression was low (p < 0.05-0.01). We performed an integrated analysis and validation and found that MYH6 expression was closely related to ICM and HF. However, whether this marker can be used as a predictor in blood samples needs further experimental verification.

BTB and CNC homology 1 inhibition ameliorates fibrosis and inflammation via blocking ERK pathway in pulmonary fibrosis.

OBJECTIVE: Patients with idiopathic pulmonary fibrosis (IPF) are still suffering from unfavorable survival. BTB and CNC homology1 (Bach1) is a regulator of oxidative stress and participates in the pathogenesis of multiple lung diseases. Thus, this study aimed to determine the effect of Bach1 knockdown on fibrosis and inflammation in pulmonary fibrosis (PF) mice and cell models. METHODS: Bleomycin induced PF mice were constructed and treated with Bach1 siRNA adenovirus (BLM + Bach1 siRNA group), control siRNA adenovirus (BLM + Control siRNA group) or normal saline (BLM group), then lung tissues were collected for Bach1 expression detection, H&E staining and Masson's trichrome staining. Afterwards, collagen type I alpha 1 chain (COL1A1) and interleukin-6 (IL-6) expressions in serum and bronchoalveolar lavage fluid (BALF) were examined. Subsequently, mouse lung fibroblasts (MLFs) were collected from PF mice and treated with TGF-ß1 to construct PF cell model, which was treated with Bach1 siRNA adenovirus (TGF-ß1 + Bach1 siRNA group) and MAP kinase (ERK) inhibitor U0126 alone (TGF-ß1 + U0126 group) or in combination (TGF-ß1 + U0126 + Bach1 siRNA group), then alpha-smooth muscle actin (α-SMA), fibronectin 1 (Fn1), COL1A1, IL-6 expressions and cell viability were detected. RESULTS: Lung tissue Bach1 mRNA and protein expressions were upregulated in PF mice compared to control mice. Bach1 knockdown reduced lung fibrosis (displayed by Masson's trichrome staining) and inflammation (displayed by H&E staining), then downregulated serum and BALF expressions of COL1A1 and IL-6 in PF mice. Subsequently, in PF cell model, Bach1 knockdown blocked ERK pathway, but did not affect Smads, c-Jun N-terminal kinase (JNK) or thymoma viral proto-oncogene 1 (Akt) pathways. Further experiments revealed that Bach1 knockdown repressed cell viability, α-SMA, Fn1, IL-6 and COL1A1 expressions in PF cell model, then ERK inhibition by U0126 enhanced these effects. CONCLUSIONS: Bach1 is involved in the PF pathogenesis via modulating ERK signaling pathway.

Causal effect between total cholesterol and HDL cholesterol as risk factors for chronic kidney disease: a mendelian randomization study.

BACKGROUND: While observational studies show an association between serum lipid levels and cardiovascular disease (CVD), intervention studies that examine the preventive effects of serum lipid levels on the development of CKD are lacking. METHODS: To estimate the role of serum lipid levels in the etiology of CKD, we conducted a two-sample mendelian randomization (MR) study on serum lipid levels. Single nucleotide polymorphisms (SNPs), which were significantly associated genome-wide with serum lipid levels from the GLGC and CKDGen consortium genome-wide association study (GWAS), including total cholesterol (TC, n = 187,365), triglyceride (TG, n = 177,861), HDL cholesterol (HDL-C, n = 187,167), LDL cholesterol (LDL-C, n = 173,082), apolipoprotein A1 (ApoA1, n = 20,687), apolipoprotein B (ApoB, n = 20,690) and CKD (n = 117,165), were used as instrumental variables. None of the lipid-related SNPs was associated with CKD (all P > 0.05). RESULTS: MR analysis genetically predicted the causal effect between TC/HDL-C and CKD. The odds ratio (OR) and 95% confidence interval (CI) of TC within CKD was 0.756 (0.579 to 0.933) (P = 0.002), and HDL-C was 0.85 (0.687 to 1.012) (P = 0.049). No causal effects between TG, LDL-C- ApoA1, ApoB and CKD were observed. Sensitivity analyses confirmed that TC and HDL-C were significantly associated with CKD. CONCLUSIONS: The findings from this MR study indicate causal effects between TC, HDL-C and CKD. Decreased TC and elevated HDL-C may reduce the incidence of CKD but need to be further confirmed by using a genetic and environmental approach.

A Hierarchical Feature Extraction Network for Fast Scene Segmentation.

Semantic segmentation is one of the most active research topics in computer vision with the goal to assign dense semantic labels for all pixels in a given image. In this paper, we introduce HFEN (Hierarchical Feature Extraction Network), a lightweight network to reach a balance between inference speed and segmentation accuracy. Our architecture is based on an encoder-decoder framework. The input images are down-sampled through an efficient encoder to extract multi-layer features. Then the extracted features are fused via a decoder, where the global contextual information and spatial information are aggregated for final segmentations with real-time performance. Extensive experiments have been conducted on two standard benchmarks, Cityscapes and Camvid, where our network achieved superior performance on NVIDIA 2080Ti.

Comparative Functional Analysis in vitro of 2 COL4A5 Splicing Mutations at the Same Site in 2 Unrelated Alport Syndrome Chinese Families.

X-linked Alport syndrome (XLAS) is a common hereditary nephropathy caused by COL4A5 gene mutations. To date, many splice site mutations have been described but few have been functionally analyzed to verify the exact splicing effects that contribute to disease pathogenesis. Here, we accidentally discovered 2 COL4A5 gene splicing mutations affecting the same residue (c.2917+1G>A and c.2917+1G>C) in 2 unrelated Chinese families. In vitro minigene assays showed that the 2 mutations produced 3 transcripts in H293T cells: one with a 96-bp deletion in exon 33, one with exon 33 skipping, and one with exon 33-34 skipping. However, fragment analysis results showed that the main splicing effects of the 2 mutations were different, the c.2917+1G>A mutation mainly activated a cryptic donor splice site in exon 33 and resulted in the deletion of 96 bp in exon 33, while the c.2917+1G>C mutation mainly caused exon 33 skipping. Our findings indicate that different nucleotide substitutions at the same residue can cause different splicing effects, which may contribute to the variable phenotype of Alport syndrome.

Association between the LIPG polymorphisms and serum lipid levels in the Maonan and Han populations.

INTRODUCTION: The Maonan population is a relatively isolated minority in China. Little is known about endothelial lipase gene (LIPG) single nucleotide polymorphisms (SNPs) and serum lipid levels in the Chinese populations. The present study aimed to detect the association of several LIPG SNPs and environmental factors with serum lipid levels in the Chinese Maonan and Han populations. METHODS: In total, 773 subjects of Maonan ethnicity and 710 participants of Han ethnicity were randomly selected from our previous stratified randomized samples. Genotypes of the LIPG rs2156552, rs4939883 and rs7241918 SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism, and then confirmed by direct sequencing. RESULTS: The allelic (rs2156552, rs4939883 and rs7241918) and genotypic (rs2156552 and rs4939883) frequencies were different between the two ethnic groups (p < 0.05-0.01). The minor allele carriers had lower apolipoprotein (Apo)A1/ApoB ratio (rs2156552 and rs7241918), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo)A1 (rs2156552) levels and higher ApoB levels (rs4939883) in the Han population, and lower HDL-C (rs2156552, rs4939883 and rs7241918) levels in the Maonan minority than the minor allele non-carriers (p < 0.0167 after Bonferroni correction). Subgroup analyses according to sex showed that the minor allele carriers had a lower ApoA1/ApoB ratio (rs2156552 and rs7241918) and higher ApoB levels (rs7241918) in Han males, and lower ApoA1 and HDL-C levels in Maonan females than the minor allele non-carriers (p < 0.0167-0.001). CONCLUSIONS: The present study demonstrates the association between the LIPG polymorphsims and serum lipid levels in the two ethnic groups. These associations might have an ethnic- and or/sex-specificity.

Circulating miR-3659 may be a potential biomarker of dyslipidemia in patients with obesity.

BACKGROUND: The present study attempted to identify potential key genes and miRNAs of dyslipidemia in obese, and to investigate the possible mechanisms associated with them. METHODS: The microarray data of GSE66676 were downloaded, including 67 obese samples from the Gene Expression Omnibus (GEO) database. The weighted gene co-expression network (WGCNA) analysis was performed using WGCNA package and grey60 module was considered as the highest correlation. Gene Ontology annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for this module were performed by clusterProfiler and DOSE package. A protein-protein interaction (PPI) network was established using Cytoscape software, and significant modules were analyzed using molecular complex detection. RESULTS: Collagen type I alpha 1 chain gene (COL1A1) had the best significant meaning. After bioinformatic analysis, we identified four miRNAs (hsa-miR-3659, hsa-miR-4658, hsa-miR151a-5p and hsa-miR-151b) which can bind SNPs in 3'UTR in COL1A1. After validation with RT-qPCR, only two miRNAs (hsa-miR-3659 and hsa-miR151a-5p) had statistical significance. CONCLUSIONS: The area of 0.806 for miR-3659 and 0.769 for miR-151a-5p under the ROC curve (AUC) may have good diagnostic value for dyslipidemia. Circulating miR-3659 may be a potential biomarker of dyslipidemia in patients with obesity.

Use of Memorial Sloan Kettering Cancer Center nomogram to guide intraoperative sentinel lymph node frozen sections in patients with early breast cancer.

BACKGROUND: We implemented selective use of frozen section (FS) to optimize accuracy and cost control in the intraoperative diagnosis of sentinel lymph node (SLN) in patients with breast cancer, guided by the Memorial Sloan Kettering Cancer Center (MSKCC) nodal metastasis risk prediction nomogram. METHODS: Surgical pathology records were reviewed, examining 2582 consecutive biopsies from 2552 patients with breast cancer to compare intraoperative FS diagnoses with postoperative final reports. We calculated sensitivity, specificity, and false-negative rates (FNRs) for various MSKCC risk levels, also analyzing axillary reoperation rates, with and without FS, and the number needed to treat (NNT) to avoid separate axillary lymph node dissection. RESULTS: The sensitivity, specificity, and FNR of FS were 84.7%, 99.9%, and 15.3%, respectively. FNR and MSKCC risk level negatively correlated (r = -0.86; P = .002). Axillary reoperation rate significantly declined if FS was done (FS: 4.0%; no FS: 36.4%; P = .002). In grouping patients by quartile of MSKCC risk, axillary reoperation rates were 16.7%, 25.1%, 38.7%, and 58.7% without FS, compared with 4.3%, 3.2%, 5.6%, 3.3% with FS and NNT correspondingly fell from 8.1 to 4.6, 3.0, and 1.8. CONCLUSIONS: A stratified decision-making algorithm based on the MSKCC risk prediction model improved the effectiveness of FS during SLN biopsy to avoid axillary reoperation.

Integrated analysis of gene expression changes associated with coronary artery disease.

BACKGROUND: This study investigated the pathways and genes involved in coronary artery disease (CAD) and the associated mechanisms. METHODS: Two array data sets of GSE19339 and GSE56885 were downloaded. The limma package was used to analyze the differentially expressed genes (DEGs) in normal and CAD specimens. Examination of DEGs through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology annotation was achieved by Database for Annotation, Visualization and Integrated Discovery (DAVID). The Cytoscape software facilitated the establishment of the protein-protein interaction (PPI) network and Molecular Complex Detection (MCODE) was performed for the significant modules. RESULTS: We identified 413 DEGs (291 up-regulated and 122 down-regulated). Approximately 256 biological processes, only 1 cellular component, and 21 molecular functions were identified by GO analysis and 10 pathways were enriched by KEGG. Moreover, 264 protein pairs and 64 nodes were visualized by the PPI network. After the MCODE analysis, the top 4 high degree genes, including interleukin 1 beta (IL1B, degree = 29), intercellular adhesion molecule 1 (ICAM1, degree = 25), Jun proto-oncogene (JUN, degree = 23) and C-C motif chemokine ligand 2 (CCL2, degree = 20) had been identified to validate in RT-PCR and Cox proportional hazards regression between CAD and normals. CONCLUSIONS: The relative expression of IL1B, ICAM1 and CCL2 was higher in CAD than in normal controls (P < 0.05-0.001), but only IL1B and CCL2 genes were confirmed after testing the gene expression in blood and/or analyzing in Cox proportional hazards regression (P < 0.05-0.001), and the proper mechanism may involve in the AGE-RAGE signaling pathway, fluid shear stress, the tumor necrosis factor (TNF) and cytokine-cytokine receptor interaction.

LIPG SNPs, their haplotypes and gene-environment interactions on serum lipid levels.

BACKGROUND: Maonan nationality is a relatively conservative and isolated minority in the Southwest of China. Little is known about the association of endothelial lipase gene (LIPG) single nucleotide polymorphisms (SNPs) and serum lipid levels in the Chinese populations. METHODS: A total of 1280 subjects of Maonan nationality and 1218 participants of Han nationality were randomly selected from our previous stratified randomized samples. Genotypes of the four LIPG SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism, and then confirmed by direct sequencing. RESULTS: Several SNPs were associated with high-density lipoprotein cholesterol (rs3813082, rs2000813 and rs2097055) in the both ethnic groups; total cholesterol and apolipoprotein (Apo) A1 (rs2000813) in Han nationality; and low-density lipoprotein cholesterol, ApoB, triglyceride (rs2097055) and ApoA1 (rs3819166) in Maonan minority (P < 0.0125 for all after Bonferroni correction). The commonest haplotype was rs3813082T-rs2000813C-rs2097055T-rs3819166A (Han, 44.2% and Maonan, 48.7%). The frequencies of the T-C-T-A, T-C-T-G, T-T-C-G and G-T-C-G haplotypes were different between the Maonan and Han populations (P < 0.05-0.001). The associations between haplotypes and dyslipidemia were also different in the Han and/or Maonan populations (P < 0.05-0.001). CONCLUSIONS: The differences in serum lipid profiles between the two ethnic groups might partly be attributed to these LIPG SNPs, their haplotypes and gene-environmental interactions. TRIAL REGISTRATION: Retrospectively registered.

LncRNA SNHG8 is identified as a key regulator of acute myocardial infarction by RNA-seq analysis.

BACKGROUND: Long noncoding RNAs (lncRNAs) are involved in numerous physiological functions. However, their mechanisms in acute myocardial infarction (AMI) are not well understood. METHODS: We performed an RNA-seq analysis to explore the molecular mechanism of AMI by constructing a lncRNA-miRNA-mRNA axis based on the ceRNA hypothesis. The target microRNA data were used to design a global AMI triple network. Thereafter, a functional enrichment analysis and clustering topological analyses were conducted by using the triple network. The expression of lncRNA SNHG8, SOCS3 and ICAM1 was measured by qRT-PCR. The prognostic values of lncRNA SNHG8, SOCS3 and ICAM1 were evaluated using a receiver operating characteristic (ROC) curve. RESULTS: An AMI lncRNA-miRNA-mRNA network was constructed that included two mRNAs, one miRNA and one lncRNA. After RT-PCR validation of lncRNA SNHG8, SOCS3 and ICAM1 between the AMI and normal samples, only lncRNA SNHG8 had significant diagnostic value for further analysis. The ROC curve showed that SNHG8 presented an AUC of 0.850, while the AUC of SOCS3 was 0.633 and that of ICAM1 was 0.594. After a pairwise comparison, we found that SNHG8 was statistically significant (P SNHG8-ICAM1 = 0.002; P SNHG8-SOCS3 = 0.031). The results of a functional enrichment analysis of the interacting genes and microRNAs showed that the shared lncRNA SNHG8 may be a new factor in AMI. CONCLUSIONS: Our investigation of the lncRNA-miRNA-mRNA regulatory networks in AMI revealed a novel lncRNA, lncRNA SNHG8, as a risk factor for AMI and expanded our understanding of the mechanisms involved in the pathogenesis of AMI.

Weighted Gene Co-Expression Network Analysis Identifies Specific Modules and Hub Genes Related to Hyperlipidemia.

BACKGROUND/AIMS: The present study attempted to identify the potential key genes and pathways of hyperlipidemia, and to investigate the possible mechanisms associated with them. METHODS: The array data of GSE3059 were downloaded, including thirteen samples of hyperlipidemia from the Gene Expression Omnibus (GEO) database. The weighted gene co-expression network analysis (WGCNA) was performed with WGCNA package, and the salmon and midnight blue modules were found as the highest correlation. Gene Ontology annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for these two modules were performed by cluster Profiler and DOSE package. A protein-protein interaction (PPI) network was established using Cytoscape software, and significant modules were analyzed using Molecular Complex Detection. RESULTS: Five genes (histone deacetylase 4, HDAC4; F2R like trypsin receptor 1, F2RL1; abhydrolase domain containing 2, ABHD2; transmembrane 4 L six family member 1, TM4SF1; and family with sequence similarity 13-member A, FAM13A) were found with a significant meaning. When their expression levels were validated with RT-qPCR, the relative expression levels were lower (HDAC4) and higher (F2RL1, ABHD2, TM4SF1 and FAM13A) in hyperlipidemia than in normal controls (P < 0.05-0.01). Subgroup analysis showed that the relative expression levels of HDAC4 were lower, whereas those of F2RL1 and ABHD2 were higher in Maonan than in Han ethnic groups (P < 0.05). CONCLUSION: Except for genetic factors and environmental exposures, epigenetic influence was another mechanism of hyperlipidemia in our study populations, which needed to further confirm.

Association between single nucleotide polymorphism rs9534275 and the risk of coronary artery disease and ischemic stroke.

BACKGROUND: The present study was to detect the association of single nucleotide polymorphism (SNP) in the breast susceptibility gene 2 (BRCA2) and the risk of coronary artery disease (CAD) and ischemic stroke (IS). METHODS: Genotypes of the BRCA2 rs9534275 in 1822 unrelated subjects (CAD, 606; IS, 569; and healthy controls, 647) were determined by the polymerase chain reaction and restriction fragment length polymorphism and then confirmed by direct sequencing. RESULTS: The genotypic and allelic frequencies of rs9534275 were significantly different between the CAD, IS patients and controls (P = 0.033 and P = 0.027; respectively). The GG, GT/GG genotypes and G allele were associated with an increased risk of CAD and IS (CAD: P = 0.005 for GG vs. TT, P = 0.004 for GT/GG vs. TT, P = 0.005 for G vs. T; IS: P = 0.003 for GG vs. TT, P = 0.005 for GT/GG vs. TT; P = 0.002 for G vs. T). The GG, GT and GT/GG genotypes in the CAD, but not in healthy controls and IS patients, were associated with an increased serum total cholesterol (TC) and apolipoprotein B (ApoB) concentration. CONCLUSIONS: The present study shows that the G allele carriers of BRCA2 rs9534275 were associated with increased serum TC and ApoB levels in the CAD patients and increased risk of CAD and IS. TRIAL REGISTRATION: Retrospectively registered.

[Evaluation of 99mTc-ECD SPECT/CT brain imaging with scenium analysis in patients with generalized anxiety disorder].

OBJECTIVE: To assess the perfusion changes in brains of patients with varying levels of generalized anxiety disorder (GAD). METHODS: A total of 38 GAD outpatients of Department of Psychiatry at our hospital from February to August, 2014 and 10 healthy controls received a 99mTC-ECD SPECT/CT scan with scenium analysis. Differences between brain perfusion and anxiety levels were analyzed by SPSS 16. 0 with one-way ANOVA, Pearson's Chi-square, t test and Spearman's correlation. RESULTS: They were grouped according to the levels of anxiety severity, i. e. mild (n = 11) , moderate (n = 16) and severe (n = 11). They had significantly lower blood flow in right superior frontal medial gyrus, right precuneus, right putamen, bilateral paracentral lobule and bilateral supplementary motor area (t = -2.19, -2.14, -2.22, -2.34, -2.08, -3.26, -2.72, P < 0.05). Individuals had significantly greater blood flow in mild group than those of control group in right olfactory (t = 2.09 P = 0.05). Individuals of moderate group had significantly lower blood flow than those of control group in left superior frontal gyrus medial orbital, right superior frontal gyrus medial orbital and left supplementary motor area, but greater in right olfactory (t = -2.16, -2.24, -2.49, 2.17, P = 0.04, 0.04, 0.02, 0.04). Individuals had lower blood flow in severe group than those of control group in left frontal lobe, right putamen, left paracentral lobule, right paracentral lobule, left precuneus, right precuneus, left parietal lobe, left precentral, right precentral, right postcentral, left rolandic operculum, left supplementary motor area, right supplementary motor area and left central region (t = -2.32, -2.11, -3.16, -2.61, -2.39, -2.18, -2.32, -2.67, -2.14, -2.11, -2.25, -4.38, -3.54, -2.38, P = 0.03, 0.05, 0.01, 0.02, 0.03, 0.04, 0.03, 0.02, 0.05, 0.05, 0.04, 0.00, 0.00, 0.03). Statistical differences existed in right middle frontal gyms orbital part (mild: 0.96 ± 0.07, moderate: 1.03 ± 0.06, severe: 0.98 ± 0.08, P = 0.04) and left paracentral (mild: 0.91 ± 0.07, moderate: 093 ± 004 severe: 0.87 ± 0.07, P = 0.02). There was a tendency of negative correlation between perfusion in right middle cingulate and paracingulate gyri, left precuneus, right precuneus and left thalamus and anxiety scores by Spearman's correlation analysis (r = -0.28, -0.28, -0.27, -0.29, P = 0.09, 0.09, 0.10, 0.07). CONCLUSION: Scenium software provides quantitative measurements for diagnosis of GAD in different anxiety levels. Also larger samples are required for confirming the results in further studies.

Associations of body roundness index with cardiovascular and all-cause mortality: NHANES 2001-2018.

Body roundness index (BRI) was associated with cardiovascular diseases. But the relationship between BRI with cardiovascular disease (CVD) mortality and all-cause mortality remains largely unknown in hypertensive patients. This prospective cohort study included patients with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 2001 through 2018, and aimed to evaluate the association between BRI with CVD mortality and all-cause mortality. A total of 15570 patients were included. Over a median follow-up of 8.0 years (interquartile range, 4.3-12.6 years), 3445 individuals died, including 1166 CVD deaths. Weighted restricted cubic spline regression results showed a nonlinear association between BRI and CVD mortality and all-cause mortality (both P for nonlinear trend <0.001). The weighted multivariate Cox proportional hazards regression showed the hazard ratio (HRs) for CVD mortality were 0.93 (95% CI: 0.84-1.03, P = 0.160) in the low levels of BRI (≤5.9) and 1.11 (95% CI: 1.05-1.19, P < 0.001) in the high levels of BRI (>5.9). Similar associations were observed for all-cause mortality, the HRs were 0.91 (95% CI: 0.87-0.96, P < 0.001) in the low levels of BRI (≤6.3) and 1.09 (95% CI: 1.05-1.13, P < 0.001) in the high levels of BRI (>6.3). This cohort study supported that BRI was nonlinearly associated with CVD mortality and all-cause mortality among patients with hypertension. The thresholds of 5.9 and 6.3 for CVD mortality and all-cause mortality, respectively, may represent intervention targets for lowering the risk of premature death, but this needs to be confirmed in large clinical trials.

Osteoarthritis and hypertension: observational and Mendelian randomization analyses.

BACKGROUND: The association between osteoarthritis (OA) and hypertension is a subject of ongoing debate in observational research, and the underlying causal relationship between them remains elusive. METHODS: This study retrospectively included 24,871 participants in the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2020. Weighted logistic regression was performed to investigate the connection between OA and hypertension. Additionally, Mendelian randomization (MR) analysis was conducted to explore the potential causal relationship between OA and hypertension. RESULTS: In the NHANES data, after adjusting for multiple confounding factors, there was no significant relationship between OA and hypertension (OR 1.30, 95% CI, 0.97-1.73, P = 0.089). However, among males, OA appeared to be associated with a higher risk of hypertension (OR 2.25, 95% CI, 1.17-4.32, P = 0.019). Furthermore, MR results indicate no relationship between multiple OA phenotypes and hypertension: knee OA (IVW, OR 1.024, 95% CI: 0.931-1.126, P = 0.626), hip OA (IVW, OR 0.990, 95% CI: 0.941-1.042, P = 0.704), knee or hip OA (IVW, OR 1.005, 95% CI: 0.915-1.105, P = 0.911), and OA from UK Biobank (IVW, OR 0.796, 95% CI: 0.233-2.714, P = 0.715). Importantly, these findings remained consistent across different genders and in reverse MR. CONCLUSIONS: Our study found that OA patients had a higher risk of hypertension only among males in the observational study. However, MR analysis did not uncover any causal relationship between OA and hypertension.

Mechanism of salidroside against coronary artery disease by network pharmacology analysis.

BACKGROUND: Rosenroot (Rhodiola rosea) is a traditional Chinese herbal medicine. It has been used to treat patients with coronary artery disease (CAD). Salidroside is the main active constituent of rosenroot. This study was designed to explore the mechanism of salidroside in treating CAD and its role in angiogenesis in CAD systematically. METHODS: In this study, potential targets related to salidroside and CAD were obtained from public databases. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO) and CellMarker enrichment analyses were performed. The binding of salidroside to angiogenesis-related targets was assessed by PyMOL and Ligplot. Furthermore, the effects of salidroside on collateral circulation were evaluated by correlation analysis of these angiogenesis-related targets with the coronary flow index (CFI), and the influence of salidroside on human umbilical vein endothelial cell (HUVEC) proliferation and migration was assessed. RESULTS: Eighty-three targets intersected between targets of salidroside and CAD. GO and KEGG analyses indicated that salidroside mainly treated CAD through angiogenesis and anti-inflammatory action. There were 12 angiogenesis-related targets of salidroside in coronary heart disease, among which FGF1 (r = 0.237, P = 2.597E-3), KDR (r = 0.172, P = 3.007E-2) and HIF1A (r = -0.211, P = 7.437E-3) were correlated with the coronary flow index (CFI), and salidroside docked well with them. Finally, cell experiments confirmed that salidroside promoted the proliferation and migration of HUVECs. CONCLUSIONS: This study revealed the potential molecular mechanism of salidroside on angiogenesis in CAD and provided new ideas for the clinical application of salidroside in the treatment of CAD.