Young and early-onset dilated cardiomyopathy with malignant ventricular arrhythmia and sudden cardiac death induced by the heterozygous LDB3, MYH6, and SYNE1 missense mutations.

BACKGROUND: The whole exome sequencing (WES) with targeted gene analysis is an effective diagnostic tool for cardiomyopathy. The early-onset sudden cardiac death (SCD) was commonly associated with dilated cardiomyopathy (DCM) induced by pathogenic genetic mutations. METHODS: In a Chinese Han family, the patient of 24 years old occurred with early-onset and DCM and died of SCD associated with ICD storms induced by repetitive ventricular tachycardia/fibrillation (VT/F). Genomic DNA samples of peripheral blood were conducted for WES and Sanger sequence. Then, we performed bioinformatics analysis for 200 genes susceptible to cardiomyopathies and arrhythmias. Further, we analyzed how the potential pathogenic mutations affecting the secondary structure, hydrophobicity, and phosphorylation of amino acids, protein properties, and their joint pathogenicity by ProtParam, SOPMA, and ORVAL algorisms. The protein-protein interaction was analyzed by STRING algorism. RESULTS: The mutations of LDB3 p.M456R, MYH6 p.S180Y, and SYNE1 p.S4607F were identified as "Damaging/Deleterious." The SYNE1 (p.S4607F) increased one of alpha helix and decreased one of beta sheet. The LDB3 (p.M456R) reduced one of beta sheet and increased one of beta turn. The MYH6 (p.S180Y) decreased two of beta sheets and four of beta turns, but significantly increased twelve coils. The hydrophobicity of amino acid residues and their adjacent sequences were decreased by LDB3 (p.M456R) and MYH6 (p.S180Y), and significantly increased by SYNE1 (p.S4607F). The mutations of LDB3 (p.M456R), SYNE1 (p.S4607F), and MYH6 (p.S180Y) resulted in the phosphorylation changes of the corresponding amino acid sites or the nearby amino acid sites. The pairwise combinations of LDB3, MYH6, and SYNE1 mutations have the high probability of causing disease, especially the highest probability for SYNE1 and LDB3 mutations. There was obviously indirect interaction of the proteins encoded by SYNE1, LDB3, and MYH6. CONCLUSIONS: The multiple heterozygous mutations of SYNE1, LDB3, and MYH6 may be associated with young and early-onset of DCM and SCD.

Predictive Factors of Hemorrhage After Thrombolysis in Patients With Acute Ischemic Stroke.

Background: Ischemic stroke has a poor prognosis and brings a ponderous burden on families and society. Hemorrhagic transformation (HT) after intravenous thrombolysis can increase the mortality of patients with ischemic stroke. Thus, finding new HT biomarkers to be applicable in clinical practice is of great importance. Methods: The related risk factors were recruited for analysis, including smoking, drinking, hyperlipidemia, diabetes, anamnesis, and pathological indicators. Moreover, the relationship between serum levels of caveolin-1, caveolin-2, and HT after rt-PA treatment were also studied. Results: We studied 306 patients with acute ischemic stroke treated with recombinant tissue type plasminogen activator (rt-PA) within 4.5 h of symptom onset. The results showed that Age ≥68 years, smoking, Atrial fibrillation, NIHSS score before thrombolysis ≥17, and systolic pressure 2 h after thrombolysis (mmHg) ≥149 increased the risks of HT after rt-PA administration. Remarkably, the concentration of caveolin-1 (ng/mL) ≤ 0.12 and caveolin-2 (ng/mL) ≤ 0.43 in serum increased the risks of HT after rt-PA administration. Conclusion: Knowledge on the risk factors associated with HT after rt-PA treatment may help develop treatment strategies and reduce the risk of HT. Caveolin-1 and caveolin-2 can be predictors of HT after rt-PA administration. These findings provide evidence for future further investigations aimed to validate these biomarkers.

An exploratory study of CT-guided percutaneous radiofrequency ablation for stage I thymoma.

BACKGROUND: Thymoma is a rare tumor that originates from thymic epithelial cells and is usually associated with myasthenia gravis. Radiofrequency ablation (RFA) is a minimally invasive and curative treatment for other tumors, but RFA has not been used for the early treatment of thymoma. METHODS: The current study included 13 patients with stage I thymoma who were not candidates for surgical resection or video-assisted thoracoscopic surgery (VATS). All patients underwent first-line CT-guided percutaneous RFA. The feasibility and therapeutic effects of the intervention were thoroughly documented. RESULTS: All tumors were completely ablated (13 / 13, 100%). During follow-up (median 80.5 months, range, 64.6-116.9 months), only 1 of the 13 patients had recurrence of thymoma (1 / 13, 7.7%) at 35.5 months after the initial ablation. There were no surgery-related deaths after RFA treatment. The most common complications were fever (13 / 13, 100%) and pain (13 / 13, 100%). There was only one patient who occurred severe puncture-related bleeding during the procedure that needed blood transfusion and intravascular embolization of the punctured-injured vessel. CONCLUSION: CT-guided percutaneous RFA for treatment of stage I thymoma is associated with minor trauma, few complications and good treatment outcomes.

Dynamic imaging and pathological changes in pig liver after MR-guided microwave ablation.

BACKGROUND: Magnetic resonance (MR)-guided microwave ablation is a well-developed technique for the treatment of tumors, especially hepatic carcinomas. However, there are no detailed reports on the changes in the MR images and histology observed after the ablation. This study aimed to dynamically map the pathological changes after ablation and the changes occurring on MR images. METHODS: We performed MR-guided microwave ablation in 10 Wuzhishan pigs and obtained an MR scan immediately after ablation (0 weeks) and at 1, 2, 3, and 4 weeks after ablation. We compared the ablation assessed on MR images to tissue specimens obtained during follow-up. RESULTS: We found no significant difference in the ablation size between MR images and tissue specimens; the mean length and width of the ablated zone were 4.27 cm and 2.42 cm, respectively, on MR images and 4.26 cm and 2.45 cm, respectively, on specimens (P > 0.05). Immediately after ablation, carbonization and cavities were observed in the center of the ablation zone. Surrounding layer cells were necrotic but maintained their original shapes. The outermost layer was inflamed, but gradually showed fibrotic characteristics. The MR images accurately reflected the exact histological tissue changes after the ablation procedure. CONCLUSION: The dynamic imaging and pathological features of liver ablation outlined in this study will provide a useful reference for patient follow-up after MR-guided microwave ablation.

Gene expression profiling: identification of gene expression in human MSC chondrogenic differentiation.

Understanding the mechanisms that govern cell fate will lead to the development of techniques for the induction of human mesenchymal stem cell differentiation into desired cell outcomes and the production of an autologous source of tissue for regenerative medicine. Here, we demonstrate that stem cells derived from adult bone marrow grown with 3D pellets take on characteristics similar to human cartilage. The NFAT signaling pathway is primarily linked to cell differentiation and influences chondrogenic differentiation. Based on our previous results that alterations in the expression of the NFATc1 gene affect chondrogenesis, we screened a microarray and identified 29 genes with altered expression, including 13 up-regulated (fold change ≥ 2) and 16 down-regulated (fold change ≤ 2) genes, compared with the control group. We then used RT-PCR to validate the chip data. Gene ontology and pathway analyses were performed on these altered genes. We found that these altered genes function in the complement and coagulation cascades, metabolism, biosynthesis, transcriptional regulation, proteolysis, and intracellular signaling pathways, such as the cytoplasmic calcineurin-dependent signaling pathway, the cyclin-dependent kinase inhibitor 2C signaling pathway, the MAPK signaling pathway, and the insulin signaling pathway. Our study suggests that these pathways may play important roles in chondrogenesis, which could be useful in the design of biomaterials.

Role of Nox2 and p22phox in Persistent Postoperative Hypertension in Aldosterone-Producing Adenoma Patients after Adrenalectomy.

Adrenal aldosterone-producing adenoma (APA), producing the salt-retaining hormone aldosterone, commonly causes secondary hypertension, which often persists after unilateral adrenalectomy. Although persistent hypertension was correlated with residual hormone aldosterone, the in vivo mechanism remains unclear. NADPH oxidase is the critical cause of aldosterone synthesis in vitro. Nox2 and p22phox comprise the NADPH oxidase catalytic core, serving to initiate a reactive oxygen species (ROS) cascade that may participate in the pathology. mRNAs of seven NADPH oxidase isoforms in APA were evaluated by RT-PCR and Q-PCR and their proteins by immunohistochemistry and Western blotting. NADPH oxidase activity was also detected. Nox2 and p22phox were especially abundant in APA. Particularly higher Nox2 and p22phox gene and protein levels were seen in APA than controls. Significant correlations between Nox2 mRNA and aldosterone synthase (CYP11B2) mRNA (R = 0.66, P < 0.01) and Nox2 protein and baseline plasma aldosterone concentration (PAC) (R = 0.503, P < 0.01) were detected in APA; however, none were found between p22phox mRNA, CYP11B2 mRNA, p22phox protein, and baseline PAC. Importantly, we found that Nox2 localized specifically in hyperplastic zona glomerulosa cells. In conclusion, our results highlight that Nox2 and p22phox may be directly involved in pathological aldosterone production and zona glomerulosa cell proliferation after APA resection.