Association between premature vascular smooth muscle cells senescence and vascular inflammation in Takayasu's arteritis.

OBJECTIVES: Arterial wall inflammation and remodelling are the characteristic features of Takayasu's arteritis (TAK). It has been proposed that vascular smooth muscle cells (VSMCs) are the main targeted cells of inflammatory damage and participate in arterial remodelling in TAK. Whether VSMCs are actively involved in arterial wall inflammation has not been elucidated. Studies have shown that cellular senescence in tissue is closely related to local inflammation persistence. We aimed to investigate whether VSMCs senescence contributes to vascular inflammation and the prosenescent factors in TAK. METHODS: VSMCs senescence and senescence-associated secretory phenotype were detected by histological examination, bulk RNA-Seq and single-cell RNA-seq conducted on vascular surgery samples of TAK patients. The key prosenescent factors and the downstream signalling pathway were investigated in a series of in vitro and ex vivo experiments. RESULTS: Histological findings, primary cell culture and transcriptomic analyses demonstrated that VSMCs of TAK patients had the features of premature senescence and contributed substantially to vascular inflammation by upregulating the expression of senescence-associated inflammatory cytokines. IL-6 was found to be the critical cytokine that drove VSMCs senescence and senescence-associated mitochondrial dysfunction in TAK. Mechanistically, IL-6-induced non-canonical mitochondrial localisation of phosphorylated STAT3 (Tyr705) prevented mitofusin 2 (MFN2) from proteasomal degradation, and subsequently promoted senescence-associated mitochondrial dysfunction and VSMCs senescence. Mitochondrial STAT3 or MFN2 inhibition ameliorated VSMCs senescence in ex vivo cultured arteries of TAK patients. CONCLUSIONS: VSMCs present features of cellular senescence and are actively involved in vascular inflammation in TAK. Vascular IL-6-mitochondrial STAT3-MFN2 signalling is an important driver of VSMCs senescence.

The challenges and benefits of public health in smart cities from a 4 M perspective.

Introduction: With the acceleration of urbanization, public health issues have become increasingly prominent in smart city construction, especially in the face of sudden public health crises. A deep research method for public health management based on a 4M perspective (human, machine, materials, methods) is proposed to effectively address these challenges. Methods: The method involves studying the impact of human factors such as population age, gender, and occupation on public health from a human perspective. It incorporates a machine perspective by constructing a public health prediction model using deep neural networks. Additionally, it analyzes resource allocation and process optimization in public health management from the materials and methods perspectives. Results: The experiments demonstrate that the public health prediction model based on deep neural networks achieved a prediction accuracy of 98.6% and a recall rate of 97.5% on the test dataset. In terms of resource allocation and process optimization, reasonable adjustments and optimizations increased the coverage of public health services by 20% and decreased the response time to public health events by 30%. Discussion: This research method has significant benefits for addressing the challenges of public health in smart cities. It can improve the efficiency and effectiveness of public health services, helping smart cities respond more quickly and accurately to potential large-scale public health events in the future. This approach holds important theoretical and practical significance.

High expression of CASP1 induces atherosclerosis.

Atherosclerosis is a chronic, progressive vascular disease. The relationship between CASP1 gene expression and atherosclerosis remains unclear. The atherosclerosis dataset GSE132651 and GSE202625 profiles were downloaded from gene expression omnibus. Differentially expressed genes (DEGs) were screened. The construction and analysis of protein-protein interaction network, functional enrichment analysis, gene set enrichment analysis, and Comparative Toxicogenomics Database analysis were performed. Gene expression heatmap was drawn. TargetScan was used to screen miRNAs that regulate central DEG. 47 DEGs were identified. According to gene ontology analysis, they were mainly enriched in the regulation of stimulus response, response to organic matter, extracellular region, extracellular region, and the same protein binding. Kyoto Encyclopedia of Gene and Genome analysis results showed that the target cells were mainly enriched in the PI3K-Akt signaling pathway, Ras signaling pathway, and PPAR signaling pathway. In the enrichment project of Metascape, vascular development, regulation of body fluid levels, and positive regulation of cell motility can be seen in the gene ontology enrichment project. Eleven core genes (CASP1, NLRP3, MRC1, IRS1, PPARG, APOE, IL13, FGF2, CCR2, ICAM1, HIF1A) were obtained. IRS1, PPARG, APOE, FGF2, CCR2, and HIF1A genes are identified as core genes. Gene expression heatmap showed that CASP1 was highly expressed in atherosclerosis samples and low expressed in normal samples. NLRP3, MRC1, IRS1, PPARG, APOE, IL13, FGF2, CCR2, ICAM1, HIF1A were low expressed in atherosclerosis samples. CTD analysis showed that 5 genes (CASP1, NLRP3, CCR2, ICAM1, HIF1A) were found to be associated with pneumonia, inflammation, cardiac enlargement, and tumor invasiveness. CASP1 gene is highly expressed in atherosclerosis. The higher the CASP1 gene, the worse the prognosis.

Appraising the value of CircRNAs for the diagnosis and prognosis of esophageal squamous cell cancer: An updated meta-analysis.

OBJECTIVE: The purpose of this study was to thoroughly assess the relevance of circular RNAs (circRNAs) in the diagnosis and prognosis of esophageal squamous cell carcinoma (ESCC)， and design a systematic review and meta-analysis. METHODS: Using Stata 14.0 software, a meta-analysis was carried out by looking for pertinent studies up to February 20, 2023, in the online databases PubMed, Embase, Web of Science, and CNKI. The clinicopathologic and prognostic data were evaluated using the combined advantage ratio (OR) and combined hazard ratio (HR), respectively. The threshold effects and publication bias were quantified using Spearman's correlation and the Deeks funnel plot asymmetry tests, respectively. RESULTS: A total of 36 pertinent studies with a literature quality score of 7 or above were included in this study. Of them, 22 papers dealt with clinicopathological characterization, 15 dealt with prognostic analysis, and 13 dealt with diagnostic analysis. The findings demonstrated that high expression of upregulated circRNAs was associated with worse clinicopathological features (tumor size: OR=3.61, 95% CI:1.45-5.78; TNM stage: OR=2.12, 95% CI:1.41-2.83; lymph node metastasis: OR=2.87, 95% CI:1.67-4.07) and worse OS (HR=1.49, 95% CI:1.26-1.77). High downregulated circRNAs expression was linked to improved clinicopathologic characteristics (TNM staging: OR=0.35, 95% CI:0.13- 0.95) and longer survival (HR=0.48, 95% CI:0.27-0.84); combined sensitivity was 0.77 (95% CI: 0.71-0.82), specificity was 0.80 (95% CI:0.74-0.86), and area under the subject operating characteristic curve (AUC) was 0.86 (95% CI:0.82- 0.88). CONCLUSION: CircRNAs are useful for ESCC patient diagnosis and prognosis, and they are anticipated to be unique potential biomarkers for ESCC clinical diagnosis.

Comparing extracellular volume fraction with apparent diffusion coefficient for the characterization of breast tumors.

PURPOSE: To investigate the feasibility of dual-energy CT (DECT)-derived extracellular volume (ECV) fraction for characterization of breast tumors, compared to apparent diffusion coefficient (ADC) and validated against histopathological findings. MATERIAL AND METHODS: The ECV fraction and ADC were prospectively assessed in patients with breast tumors using chest DECT and breast MRI. The diagnostic performance of ECV fraction and ADC was accessed in predicting breast histopathological subtypes and pathological complete response (pCR) status. Histopathological sections were analyzed by digital image analysis. Pearson's correlation analysis was used to correlate between DECT and histopathological ECV fractions. RESULTS: This study included 271 patients, with 314 breast lesions (61 benign and 253 malignant). The ECV fraction and ADC showed comparable area under the curve (AUC) for distinguishing benign from malignant lesions (p = 0.123) and invasive carcinoma from ductal carcinoma in situ (p = 0.115). There were significant differences in ECV fraction between different hormone receptors and Ki67 states (p = 0.001 âˆ¼ 0.014), while ADC values only differed among various Ki67 states (p < 0.001). The ECV fraction was lower (p = 0.007), ADC was higher (p = 0.013) in pCR than in non-pCR group, with an AUC of 0.748 and 0.730 (p = 0.887), respectively. There was a positive correlation between DECT and histopathological ECV fractions (r = 0.615, p < 0.01). CONCLUSIONS: Routine chest DECT-derived ECV fraction is a viable quantitative imaging biomarker for predicting histopathological subtypes and pCR in patient with breast tumors, and correlated well with histopathology finding.