Elastic Registration Algorithm Based on Three-dimensional Pulmonary MRI in Quantitative Assessment of Severity of Idiopathic Pulmonary Fibrosis.

PURPOSE: To quantitatively analyze lung elasticity in idiopathic pulmonary fibrosis (IPF) using elastic registration based on 3-dimensional pulmonary magnetic resonance imaging (3D-PMRI) and to assess its' correlations with the severity of IPF patients. MATERIAL AND METHODS: Thirty male patients with IPF (mean age: 62±6 y) and 30 age-matched male healthy controls (mean age: 62±6 y) were prospectively enrolled. 3D-PMRI was acquired with a 3-dimensional ultrashort echo time sequence in end-inspiration and end-expiration. MR images were registered from end-inspiration to end-expiration with the elastic registration algorithm. Jacobian determinants were calculated from deformation fields on color maps. The log means of the Jacobian determinants (Jac-mean) and Dice similarity coefficient were used to describe lung elasticity between 2 groups. Then, the correlation of lung elasticity with dyspnea Medical Research Council (MRC) score, exercise tolerance, health-related quality of life, lung function, and the extent of pulmonary fibrosis on chest computed tomography were analyzed. RESULTS: The Jac-mean of IPF patients (-0.19, [IQR: -0.22, -0.15]) decreased (absolute value), compared with healthy controls (-0.28, [IQR: -0.31, -0.24], P<0.001). The lung elasticity in IPF patients with dyspnea MRC≥3 (Jac-mean: -0.15; Dice: 0.06) was significantly lower than MRC 1 (Jac-mean: -0.22, P=0.001; Dice: 0.10, P=0.001) and MRC 2 (Jac-mean: -0.21, P=0.007; Dice: 0.09, P<0.001). In addition, the Jac-mean negatively correlated with forced vital capacity % (r=-0.487, P<0.001), forced expiratory volume 1% (r=-0.413, P=0.004), TLC% (r=-0.488, P<0.001), diffusing capacity of the lungs for carbon monoxide % predicted (r=-0.555, P<0.001), 6-minute walk distance (r=-0.441, P=0.030) and positively correlated with respiratory symptoms (r=0.430, P=0.042). Meanwhile, the Dice similarity coefficient positively correlated with forced vital capacity % (r=0.577, P=0.004), forced expiratory volume 1% (r=0.526, P=0.012), diffusing capacity of the lungs for carbon monoxide % predicted (r=0.435, P=0.048), 6-minute walk distance (r=0.473, P=0.016), final peripheral oxygen saturation (r=0.534, P=0.004), the extent of fibrosis on chest computed tomography (r=-0.421, P=0.021) and negatively correlated with activity (r=-0.431, P=0.048). CONCLUSION: Lung elasticity decreased in IPF patients and correlated with dyspnea, exercise tolerance, health-related quality of life, lung function, and the extent of pulmonary fibrosis. The lung elasticity based on elastic registration of 3D-PMRI may be a new nonradiation imaging biomarker for quantitative evaluation of the severity of IPF.

Copy number variation analysis of m6 A regulators identified METTL3 as a prognostic and immune-related biomarker in bladder cancer.

PURPOSE: Growing evidence has demonstrated an indispensable role for N6 -methyladenosine (m6 A) in human diseases, but the copy number variations (CNVs) of m6 A regulatory genes in bladder cancer (BLCA) remains largely unknown. METHODS: We investigated the CNVs on all known m6 A regulatory genes using the Cancer Genome Atlas (TCGA) database. The association between CNV events and clinicopathological as well as molecular characteristics of BLCA patients were explored. Gene set enrichment analysis (GSEA) was implemented to reveal relative cellular processes. Association between m6 A regulatory genes and immune infiltrates was analyzed by The Tumor Immune Estimation Resource (TIMER) database. RESULTS: CNV events of m6 A regulatory genes were frequently observed in BLCA. CNVs of METTL3, METTL14, and METTL16 correlated with molecular characteristics of BLCA patients including TP53 mutation. CNVs of METTL3 associated with the overall survival (OS) of BLCA patients. METTL3 was also associated with several cancer-related cellular processes, including mitotic spindle assembly, G2/M checkpoint, and E2F targets signaling pathway. Besides, the CNVs of m6 A regulatory genes were correlated with specific kinds of immune infiltrates. CONCLUSIONS: There are significant correlations between m6 A regulatory genes with CNVs and clinicopathological characteristics. METTL3 with CNVs were associated with the immune infiltrates and performed as a prognostic marker in BLCA.

Multi-omics analysis of copy number variations of RNA regulatory genes in soft tissue sarcoma.

AIMS: RNA regulatory genes were closely associated with tumorigenesis and prognosis in multiple tumors. Copy number variation (CNV) is a frequent characteristic in soft tissue sarcomas (STS). However, little is known regarding their possible roles in STS. MAIN METHODS: RNA sequence profiles and CNV data of 255 STS patients were downloaded from the Cancer Genome Atlas (TCGA). The correlation analysis involved CNVs of RNA regulatory genes, patient survival, immune infiltration, and DNA methylation. Drug sensitivity (IC50) was analyzed and validated by MTT assays in STS cell lines. KEY FINDINGS: CNV events were frequently observed in all kinds (m6A, m5C, ac4C, m1A, m3C, m6Am, m7G, and Ψ) of RNA regulatory genes. Diploid copy number (CN) of METTL4 was associated with better overall survival (OS) in STS and the subtypes (leiomyosarcoma, LMS; dedifferentiated liposarcoma, DDLPS). In STS and LMS, diploid CN of METTL4 was significantly associated with higher infiltration fraction of resting mast cells. In STS and DDLPS, diploid CN of METTL4 possessed lower methylation level in CpG site of cg12105018, which represented better OS. Besides, sensitive drugs for STS cell lines were analyzed according to lower IC50 for the loss CN of METTL4. Temozolomide and Olaparib were identified. Further validation by MTT assays demonstrated that GCT was the most sensitive cell line to both Temozolomide and Olaparib. SIGNIFICANCE: CNV of METTL4 could be a prognostic biomarker for STS by potentially influencing mast cell infiltration and DNA methylation. Besides, STS with loss CN of METTL4 would be sensitive to Temozolomide and Olaparib.

Bioinformatics analysis integrating metabolomics of m6A RNA microarray in intervertebral disc degeneration.

Aim: To explore the potential functions and mechanism of N6.methyladenosine (m6A) abnormality of RNAs in nucleus pulposus from the intervertebral disc degeneration (IDD). Materials & methods: We performed rat model, m6A epitranscriptomic microarray, bioinformatics analysis and metabolomics. Results: In IDD, most of the differentially methylated RNAs showed a significant demethylation situation. The competing endogenous RNA network LOC102555094/miR-431/GSK-3ß combining downstream Wnt pathway were identified in bioinformatics analysis. For metabolomics, activation of Wnt pathway led to reprogramming of glucose metabolism and enzyme activation of PKM2. Finally, quantitative real-time PCR and methylated RNA immunoprecipitation coupled with quantitative real-time PCR revealed the positive correlation between demethylation of LOC102555094 and expression of both FTO and ZFP217. Conclusion:LOC102555094 might be demethylated by ZFP217, activating FTO and LOC102555094/miR-431/GSK-3ß/Wnt played a crucial role in IDD.

Anatomical variations of the aortic arch branches in a sample of Chinese cadavers: embryological basis and literature review.

OBJECTIVES: The aim of this study is to determine the incidence and explore the types of aortic arch branch variations found in our cadavers. METHODS: The types and incidence of aortic branch variations in 120 cadavers were analysed after careful dissection. RESULTS: One hundred and six of 120 cadavers had normal aortic arch branches and gave rise to usual branches, namely the brachiocephalic trunk, the left common carotid artery and the left subclavian artery. The remaining 14 cadavers had 2 basic types of branch variations, thus accounting for an incidence of 11.67%. A total of 9 aortic arches emitted 4 branches; the brachiocephalic trunk, the left common carotid artery, the left vertebral artery and the left subclavian artery (incidence 7.5%). The second subgroup of 5 cadavers also emitted 4 aortic branches: the right common carotid artery, the left common carotid artery, the left subclavian artery and the right subclavian artery (incidence 4.16%). In this group, the right subclavian artery sprung as a distal branch of the aortic arch (descending), thus making a vascular ring that takes a superoposterior course round the back of the trachea and the oesophagus to reach the right side. There was a single cadaver, different from the other 4 aortic branches of the second group which had a common origin for the common carotid arteries, while the left subclavian artery and distally placed right subclavian artery were present. We did not observe any Kommerell's aortic diverticula. CONCLUSIONS: The variations of aortic arch branching are complex and diverse due to varied possible alterations in the embryological processes. There is an imperative need for further research on these variations to elucidate the possible relationships with clinical diagnostic or surgical events.