Heart failure (HF) is a disease with high morbidity and mortality. In patients with HF, decreased cardiac output and blood redistribution results in decreased intestinal perfusion and destruction of intestinal barrier. Microorganisms and endotoxins can migrate into the blood circulation, aggravating systemic inflammation and HF. Trimethylamine N-oxide (TMAO) is highly closed to the occurrence of HF. However, the exact mechanism between TMAO and HF remains unclear. To investigate the role of TMAO in transverse-tubule (T-tubule) in the cultured cardiomyocytes. T-tubule imaging and analysis detected T-tubule network in cardiomyocytes. Ca 2+ handling dysfunction was identified by confocal Ca 2+ imaging. Tubulin densification and polymerization were assessed by western blot and immunofluorescent staining of cardiomyocytes. TMAO induced T-tubule network damage in cardiomyocytes and Ca 2+ handling dysfunction in cardiomyocytes under the TMAO stress via promoting tubulin densification and polymerization and therefore Junctophilin-2 (JPH2) redistribution. Mice treated with TMAO represented cardiac dysfunction and T-tubule network disorganization. TMAO impairs cardiac function via the promotion of tubulin polymerization, subsequent translocation of JPH2, and T-tubule remodeling, which provides a novel mechanism for the relationship between HF and elevated TMAO.
Background: There have been few reports of mutations in the beta-myosin heavy chain (MYH7) gene in hypertrophic cardiomyopathy (HCM), which is associated with sudden cardiac death caused by HCM. This study aimed to screen the mutation sites in the sarcomeric gene MYH7 in Chinese patients with HCM. We also planned to analyze the pathogenicity of the mutation site as well as its significance in clinical and forensic medicine. Methods: From January 2006 to June 2017, autopsy cases were collected from the Department of Pathology, the Affiliated Hospital of Qingdao University. The experiment was to detect MYH7 gene status in formalin-fixed paraffin-embedded tissues from 18 independent autopsy cases who suffered HCM related sudden death (fatal HCM) and 20 cases without cardiomyopathy. Common mutation exon fragments of MYH7 gene were amplified by polymerase chain reaction. The end-of-deoxygenation method and gene cloning method were further performed to analyze the mutation sites. Homologous comparison among mutant sites was conducted using BLAST online database. Results: The 1336th nucleotide of MYH7 gene at exon 14 was converted from T to G in one HCM case, resulting in the conversion of threonine (Thr) at position 446 to proline (Pro). In another case, the 1402th nucleotide at exon 14 was converted from T to C, resulting in the conversion of phenylalanine (Phe) at position 468 to leucine (Leu). Homologous comparison results showed that the two amino acid residues of Thr446 and Phe468 are highly conserved among different species. Conclusions: Our results showed fatal HCM harbored mutations of Thr446Pro and Phe468Leu in the MYH7 gene. It is significant for clinical and forensic medicine to further explore the functions and detailed mechanisms of these mutations.
Background To compare the efficacy and safety of focused ultrasound cycloplasty (UCP) and transscleral cyclophotocoagulation (TSCP) in the treatment of refractory glaucoma in a Chinese population. Methods We retrospectively compared twenty-eight eligible patients with refractory glaucoma, who were divided into the UCP group and TSCP group. Patients in these two groups underwent a corresponding procedure from June 2018 to February 2019. The intraocular pressure (IOP), visual acuity, the number of anti-glaucoma agents used and complications were reviewed and compared between groups. Proper statistical methods were selected according to comparison models under IBM SPSS 25 software. Results After the 12-months follow-up, postoperative IOP and number of anti-glaucoma agents used in the two groups were both reduced than the baseline level, and the differences were statistically significant (P < 0.05). There were no significant differences in IOP, number of anti-glaucoma agents and the best-corrected visual acuity between the two groups at each follow-up time point (P>0.05). In terms of complications, the pain at 1 day after surgery in the UCP group was significantly milder than that in the TSCP group (P < 0.05). And there were no significant differences in other complications between the two groups (P > 0.05). Conclusions Both UCP and TSCP are safe and effective methods for the treatment of refractory glaucoma. Nevertheless, pain is less severe after UCP.
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