Quantitative late gadolinium enhancement cardiac magnetic resonance analysis of the relationship between ablation parameter and left atrial tissue lesion following pulmonary vein isolation.

Background: The impact of ablation parameters on acute tissue lesion formation after pulmonary vein isolation (PVI) has not been sufficiently evaluated in patients with atrial fibrillation. Radiofrequency ablation lesion can be visualized by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). We sought to quantitatively analyze the relationship between ablation parameter and tissue lesion following PVI at different segments of pulmonary vein (PV) using LGE-CMR. Methods: Twenty-one patients with atrial fibrillation who underwent PVI procedure were retrospectively enrolled. All patients underwent LGE-CMR examination within 3 days after radiofrequency ablation. Ablation parameters during PVI were documented, including lesion size index (LSI), force-time integral (FTI), power, contact force, temperature, and time of duration. The ablation point was projected onto 3-dimensional (3D) left atrial shell constructed base on LGE-CMR and corresponding image intensity ratio (IIR) was calculated on the same shell. A tissue lesion point was defined when the LGE-CMR IIR was > 1.2. Results: In total, 1,759 ablation points were analyzed. The ablation parameters and IIRs for each PV segment were significantly different (P < 0.0001). IIRs corresponding to ablation points at posterior of PV tended to be higher than those at non-posterior of PV when similar ablation parameters were applied during ablation. LSI was a better predictor of tissue lesion existence following PVI than FTI, contact force, power, temperature, and duration time at non-posterior wall of PV. The IIR showed positive correlation with LSI at non-posterior wall of PV (non-posterior of right PV, r = 0.13, P = 0.001, non-posterior of left PV, r = 0.26, P < 0.0001). Conclusion: When similar ablation parameters were applied during PVI, the posterior wall of PV had more severe tissue lesion than non-posterior wall of PV. Therefore, it was reasonable to decrease ablation energy at posterior wall of PV. Moreover, LSI was a better index to reflect tissue lesion quality following PVI at non-posterior of PV.

Shikonin suppresses colon cancer cell growth and exerts synergistic effects by regulating ADAM17 and the IL­6/STAT3 signaling pathway.

Signal transducer and activator of transcription 3 (STAT3) activation is associated with drug resistance induced by anti­epidermal growth factor receptor (anti­EGFR) therapy in the treatment of colon cancer. Thus, the combined inhibition of EGFR and STAT3 may prove beneficial for this type of cancer. STAT3 has been proven to play a critical role in colon cancer initiation and progression, and is considered the primary downstream effector driven by interleukin­6 (IL­6). A disintegrin and metalloproteinase 17 (ADAM17), documented as an oncogene, catalyzes the cleavage of both EGF and IL­6R, inducing EGFR signaling and enabling IL­6 trans­signaling to activate STAT3 in a wide range of cell types to promote inflammation and cancer development. As a natural product, shikonin (SKN) has been found to function as an antitumor agent; however, its role in the regulation of ADAM17 and IL­6/STAT3 signaling in colon cancer cells remains unknown. In the present study, it was found that SKN inhibited colon cancer cell growth, suppressed both constitutive and IL­6­induced STAT3 phosphorylation, and downregulated the expression of ADAM17. ADAM17 expression was not altered in response to STAT3 knockdown, while IL­6­induced STAT3 activation did not induce ADAM17 transcripts. Furthermore, it was demonstrated that SKN did not affect the expression of key proteins involved in the maturation and degradation of ADAM17. SKN decreased ADAM17 expression possibly through reactive oxygen species (ROS)­mediated translational inhibition, as evidenced by the increased ADAM17 mRNA and phosphorylation levels of eukaryotic initiation factor 2α (eIF2α). The expression of ADAM17 and p­eIF2α was reversed by N­acetylcysteine (NAC, a ROS scavenger). Taken together, these results indicate that the concurrent inhibition of ADAM17 and IL­6/STAT3 signaling by SKN may synergistically contribute to the suppression of colon cancer cell growth.

A splicing LMNA mutation causing laminopathies accompanied by aortic valve malformation.

BACKGROUND: Laminopathies caused by LMNA gene mutations are characterized by different clinical manifestations. Among them, cardiac involvement is one of the most severe phenotypes. CASE PRESENTATION: A 30-year-old man visited the hospital because of palpitations, shortness of breath, and fatigue. He also had muscular dystrophy, joint contractures, scoliosis, and mild dysphagia. A novel de novo heterozygous LMNA splice variant (c.810+1G>T) with dilated cardiomyopathy, Emery-Dreifuss muscular dystrophy, and progressive cardiac conduction defect was identified by genetic analysis. The patient also presented with congenital aortic valve malformation, which has never been reported in laminopathies. CONCLUSIONS: The LMNA mutation (c.810+1G>T) was identified for the first time, enriching the mutation spectrum of the LMNA gene. The correlation between an LMNA mutation and congenital aortic valve malformation deserves further study.