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Background This study evaluates the health-related quality of life (HRQoL) of persons with diffuse large B-cell lymphoma (DLBCL) by using EQ-5D-5L and SF-6Dv2 and compares the measurement properties of the two instruments. Method DLBCL patients were identified via a patient group and were surveyed using web-based questionnaires. Demographic information, socioeconomic status (SES), clinical characteristics, and EQ-5D-5L and SF-6Dv2 responses were collected and statistically described. The association between the EQ-5D-5L and SF-6Dv2 dimensions were analyzed using the Spearman's correlation coefficient, whereas the correlation of the utility scores was evaluated using Pearson's correlation coefficient. The agreement between the responses of the two instruments were examined using a Bland–Altman (B-A) plot. A one-way analysis of variance (ANOVA) was performed to compare the utility scores across subgroups in different clinical states (a t-test was used if there were two subgroups). In addition, the graded response model (GRM) was used to describe the discrimination ability and difficulty characteristics of the dimensions in the two instruments. Results In total, 582 valid responses were collected, among which 477 respondents were associated with initial-treatment and 105 respondents were relapsed/refractory (RR) patients. The mean (standard deviation [SD]) EQ-5D-5L and SF-6Dv2 utility scores of the DLBCL patients were 0.828 (0.222) and 0.641 (0.220), respectively. The correlation between the EQ-5D-5L and SF-6Dv2 dimensions ranged from 0.299 to 0.680, and the correlation between their utility scores was 0.787. The B-A plot demonstrated an acceptable but not strong agreement between EQ-5D-5L and SF-6Dv2 utility scores. The GRM model results indicated that all dimensions of each instrument were highly discriminating overall, but EQ-5D-5L had suboptimal discriminative power among patients with good health. Conclusion Both the EQ-5D-5L and SF-6Dv2 showed valid properties to assess the HRQoL of DLBCL patients. However, utility scores derived from the two instruments had substantial difference, thereby prohibiting the interchangeable use of utilities from the two instruments.

One of the pathogenic causes of thoracic aortic aneurysm (TAA), a dangerous vascular condition that can cause aortic rupture, is autoimmune disorders. Currently, immune cell clustering is becoming more and more refined, and the specific immune cell phenotypes involved are yet unknown. Here, we want to clarify the causal link between TAA risk and 731 immune cell traits. There was a Mendelian randomization analysis (MR). We discovered that the presence of TAA led to an increase in CD45 on CD33 − HLA-DR − myeloid cells, an increase in CD45 on natural killer cells, and a decrease in FSC-A on granulocytes after applying FDR correction. Our research also revealed a strong correlation between the incidence of TAA and an increase in immune cells with CD3 on CD39 + CD4 + , and CD25 on IgD − CD27 − phenotypes. Through genetic techniques, our research has shown the intimate relationship between immune cells and TAA, offering direction for future clinical investigations.

To investigate the mechanism of curcumin (CUR) on vascular calcification (VC), we screen for common targets of CUR and atherosclerosis and verify the targets genes in vivo and in vitro experiments. The common targets of CUR and AS were screened and obtained using different databases. These target genes were analyzed by GO and KEGG pathway enrichment analysis. PPI network analysis was performed and to analyze the key targets. A rat VC model was constructed and CUR was fed for three weeks. The changes of vascular structure and calcium salt deposition were observed in H&E and Von Kossa staining. Further, the expression of these target proteins was detected in the primary VSMCs of VC. The 31 common targets were obtained. GO functional enrichment analysis obtained 1284 terms and KEGG pathway enriched 66 pathways. The key genes were identified in the cytoHubba plugin. The molecular docking analysis showed that CUR bound strongly to EGFR, STAT3 and BCL2. The animal experiments showed the deposition calcium salt reduced by the CUR administration. These proteins BMP2, RUNX2, EGFR, STAT3 and BAX expression were upregulated in VC group and CUR attenuated the upregulated expression. The signal protein Akt and p65 expression increased in VC group and decreased in CUR group. We identified some common target genes of CUR and AS and identified these key genes. The anti-VC effect of CUR was associated with the inhibition of upregulation of EGFR, STAT3 and RUNX2 expression in VSMCs.

Objective. We investigated the effects of resveratrol (Res) and MCC950 on the pyroptosis of vascular smooth muscle cells (VSMCs) and the potential pathway. Methods and Results. Compared with the control (Con) group, the atherosclerosis (AS) group showed calcified nodules, which suggested that the calcification medium induced the calcification of VSMCs. VSMCs showed proliferative activity and significantly attenuated calcification under treatment with 10 μmol/L Res. The calcium salt was detected by alizarin red S staining. Res and MCC950 downregulated the calcification, inflammatory, pyroptosis, and transcription factor-related indicators all decreased by RT-qPCR with Western blot and immunofluorescence. The results showed that Res and MCC950 refrained the calcification of VSMCs and that Res has a better effect than MCC950. Plaques and calcium salt deposits were present in the carotid region in the control group. More calcium salt deposits were evident in the plaques of the Par group by HE staining and alizarin red S staining. The calcification indexes BMP2, Runx2, and related indexes declined by immunofluorescence, which showed parthenolide-inhibited AS. The related protein expressions were consistent with the expression of the cell experiments. Conclusion. Our data demonstrated that inflammatory response and pyroptosis exacerbate AS and unravel the link between VSMCs and the progression of AS lesions. Res and MCC950 inhibited the calcification of VSMCs by regulating NF-κB/NLRP3/IL-1β signaling axis. P53 can exacerbate the AS lesions by acting on NLRP3 inflammasome and pyroptosis. Our findings supported the clinical applications of Res and MCC950 in VSMCs individuals to counteract pyroptosis and AS, and P53 inhibitors also can be a potential treatment for AS.

Background Atherosclerosis (AS) is a chronic inflammatory disease that might induce severe cardiovascular events, such as myocardial infarction and cerebral infarction. These risk factors in the pathogenesis of AS remain uncertain and further research is needed. This study aims to explore the potential molecular mechanisms of AS by bioinformatics analyses. Methods GSE100927 gene expression profiles, including 69 AS samples and 35 healthy controls, were downloaded from Gene Expression Omnibus database and indenfied for key genes and pathways in AS. Results A total of 443 differentially expressed genes (DEGs) between control and AS were identified, including 323 down-regulated genes and 120 up-regulated genes. The Gene ontology terms enriched by the up-regulated DEGs were associated with the regulation of leukocyte activation, endocytic vesicle, and cytokine binding, while the down-regulated DEGs were associated with negative regulation of cell growth, extracellular matrix, and G protein-coupled receptor binding. KEGG pathway analysis showed that the up-regulated DEGs were enriched in Osteoclast differentiation and Phagosome, while the down-regulated DEGs were enriched in vascular smooth muscle contraction and cGMP-PKG signaling pathway. Using the modular analysis of Cytoscape, we identified 3 modules mainly involved in Leishmaniasis and Osteoclast differentiation. The GSEA analysis showed the up-regulated gene sets were enriched in the ribosome, ascorbated metabolism, and propanoate metabolism. The LASSO Cox regression analysis showed the top 3 genes were TNF, CX3CR1, and COL1R1. Finally, we found these immune cells were conferred significantly higher infiltrating density in the AS group. Conclusions Our data showed the pathway of Osteoclast differentiation and Leishmaniasis was involved in the AS process and we developed a three-gene model base on the prognosis of AS. These findings clarified the gene regulatory network of AS and may provide a novel target for AS therapy.

Thoracic aortic aneurysm (TAA) refers to the abnormal dilation of the thoracic aorta above the diaphragm, and dyslipidemia has been implicated in increasing the risk of its development. The emergence of lipidomics technology has deepened our understanding of this disease. In this study, we utilized Mendelian randomization analysis (MR) to elucidate the causal relationship between TAA and plasma lipidome. We found a strong correlation between increased levels of phosphatidylethanolamine (18:0_18:2) in the blood and occurrence of TAA. Our research also revealed that TAA may lead to a decrease in levels of phosphatidylcholine (16:0_18:3), phosphatidylcholine (18:2_20:4), and phosphatidylcholine (O − 17:0_17:1) in the plasma. Through genetic techniques, our study has shed light on the close relationship between TAA and plasma lipidome, providing direction for future clinical research.

The blockade of renin–angiotensin II system has been shown to reduce morbidity and mortality in hypertension, atherosclerosis, diabetes and chronic kidney disease. Since vascular calcification (VC) is commonly found in these diseases, the aim of this study was to examine whether or not losartan, a widely used angiotensin II receptor blockers, inhibits VC in rats in vivo. A rat model of VC was generated by treating rats with a combination of warfarin and vitamin K1. Two weeks after the treatments, the rats were treated with vehicle or without losartan (100 ng/kg/day) for 2 weeks. At the end of the experiments, aortic arteries were isolated for the examination of calcification morphology, mRNA and protein expression of BMP2 and Runx2, and osteoblast differentiation. Warfarin and vitamin K instigated vascular remodeling with calcified plaques in the aortic arteries in rats. Losartan significantly attenuated warfarin- and vitamin K-induced vascular injury and calcification. Consistently, losartan suppressed the levels of mRNA and protein expression of BMP2 and Runx2, two key factors for VC. Further, vascular calcified lesion areas expressed angiotensin II 1 receptor (AT1R). Finally, losartan treatment significantly inhibited apoptosis in vascular smooth muscle cell (VSMC) in rat arteries. We conclude that losartan suppresses VC by lowering the expression of AT1R, Runx2 and BMP2, and by inhibiting the apoptosis of VSMC in rat aortic arteries.

Recent findings suggest that in response to repair-to-injury bone marrow mesenchymal stem cells (BMSCs) participate in the process of angiogenesis. It is unclear what role BMSCs play in the structure of the vessel wall. In present study, we aimed to determine whether BMSCs had the capacity of endothelial cells (ECs). BMSCs were separated and cultured. FACS and RT-PCR analysis confirmed the gene expression phenotype. The capacity of migration and adhesion and the ultrastructure of BMSCs were examined. The effect of BMSCs transplantation on the vascular repair was investigated in a murine carotid artery-injured model. BMSCs could express some markers and form the tube-like structure. The migration and adhesion capacity of BMSCs increased significantly after stimulated. In addition, BMSCs had the intact cell junction. In vivo the local transfer of BMSCs differentiated into neo-endothelial cells in the injury model for carotid artery and contributed to the vascular remodeling. These results showed that BMSCs could contribute to neointimal formation for vascular lesion and might be associated with the differentiation into ECs, which indicated the important therapeutic implications for vascular diseases.

Vascular calcification, characterized by the active deposition of calcium phosphate in the vascular walls, is commonly observed in aging, diabetes mellitus and chronic kidney disease. This process is mediated by different cell types, including vascular stem/progenitor cells. The anti-aging protein klotho may act as an inhibitor of vascular calcification through direct effects on vascular stem/progenitor cells with osteogenic differentiation potential. A better understanding of the possible effects of klotho on vascular stem/progenitor cells may provide novel insight into the cellular and molecular mechanisms of klotho deficiency-related vascular calcification and disease. The klotho protein may be considered as a promising therapeutic agent for treating vascular calcification and disease and calcification-related vascular diseases.

This study evaluates the health-related quality of life (HRQoL) of persons with diffuse large B-cell lymphoma (DLBCL) by using EQ-5D-5L and SF-6Dv2 and compares the measurement properties of the two instruments. DLBCL patients were identified via a patient group and were surveyed using web-based questionnaires. Demographic information, socioeconomic status (SES), clinical characteristics, and EQ-5D-5L and SF-6Dv2 responses were collected and statistically described. The association between the EQ-5D-5L and SF-6Dv2 dimensions were analyzed using the Spearman's correlation coefficient, whereas the correlation of the utility scores was evaluated using Pearson's correlation coefficient. The agreement between the responses of the two instruments were examined using a Bland-Altman (B-A) plot. A one-way analysis of variance (ANOVA) was performed to compare the utility scores across subgroups in different clinical states (a t-test was used if there were two subgroups). In addition, the graded response model (GRM) was used to describe the discrimination ability and difficulty characteristics of the dimensions in the two instruments. In total, 582 valid responses were collected, among which 477 respondents were associated with initial-treatment and 105 respondents were relapsed/refractory (RR) patients. The mean (standard deviation [SD]) EQ-5D-5L and SF-6Dv2 utility scores of the DLBCL patients were 0.828 (0.222) and 0.641 (0.220), respectively. The correlation between the EQ-5D-5L and SF-6Dv2 dimensions ranged from 0.299 to 0.680, and the correlation between their utility scores was 0.787. The B-A plot demonstrated an acceptable but not strong agreement between EQ-5D-5L and SF-6Dv2 utility scores. The GRM model results indicated that all dimensions of each instrument were highly discriminating overall, but EQ-5D-5L had suboptimal discriminative power among patients with good health. Both the EQ-5D-5L and SF-6Dv2 showed valid properties to assess the HRQoL of DLBCL patients. However, utility scores derived from the two instruments had substantial difference, thereby prohibiting the interchangeable use of utilities from the two instruments.