OBJECTIVE: To investigate the genetic etiology of six adult patients with Dilated cardiomyopathy (DCM), and analyze the structure of the identified variants, for providing reference for the diagnosis of DCM. METHODS: Six adult patients with DCM (patients 1-6) admitted to the Department of Cardiology of Zhumadian Central Hospital from January 2023 to December 2023 were recruited. Clinical data of the patients were retrospectively collected. And 5 mL of peripheral blood was collected from each patient. Pathogenic variants of the patients were detected by whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. The possible functional significance of the identified missense variants was evaluated using software including SIFT, PolyPhen-2 and Mutation Taster. Specific regions of the MYBPC protein encoded by the MYBPC3 gene from different species were aligned using Mutation Taster. The wild-type and mutant MYBPC proteins were constructed using homologous modeling software MODELLER v10.4 and three-dimensional structures were visualized using PyMOL software. The molecular interaction between MYBPC-C5 domain and myosin with or without the mutation was further analyzed using ZDOCK module in Discovery Studio 2019 software. Pathogenicity ratings for the detected variant sites were performed in accordance with the Standards and Guidelines for the Interpretation of Sequence variants by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG Guidelines). This study was reviewed and approved by the Ethics Committee of Zhumadian Central Hospital (Approval No. 2022092007). RESULTS: The six DCM patients had typical symptoms of heart failure, and echocardiography showed whole-heart dilation and decreased ventricular wall motion, left ventricular end-diastolic dimension (LVEDD) was 59-74 mm, left ventricular ejection fraction (LVEF) was 35%-43%, and left ventricular fractional shortening (LVFS) was 17%-28%. Variations of the DCM related genes, including a c.98473A>T (p.Lys32825*) variation of the TTN gene and a c.1976T>C (p.Ile659Thr) variation of the MYBPC3 gene, were identified in two patients. Multiple software predicted that both mutations were deleterious. MYBPC3-Ile659Thr mutation affected the highly conserved residue within the C5 domain of MYBPC. Three-dimensional structural analysis of homologous modeling revealed the alterations in amino acid properties and interactions with surrounding amino acids caused by the MYBPC3-Ile659Thr mutation. Further molecular docking analysis showed that the Ile659Thr mutation altered both the hydrogen bond and salt-bridge interactions between the MYBPC-C5 domain and the ligand myosin. CONCLUSION Two mutations associated with DCM were identified in this study. The abnormal conformation of the mutant protein further affected its interaction with the ligand myosin, resulting in the phenotype of DCM.
Humans ; Cardiomyopathy, Dilated/genetics* ; Male ; Adult ; Female ; Carrier Proteins/chemistry* ; Middle Aged ; Mutation ; Exome Sequencing ; Mutation, Missense ; Retrospective Studies ; Myosin Binding Protein C

Objective:To investigate the clinical outcome of extended Carlson approach to plate fixation of tibial plateau fracture with combined posterolateral and anterolateral fragments.Methods:A retrospective case series study was made on 16 patients with tibial plateau fracture with combined posterolateral and anterolateral fragments admitted to First Affiliated Hospital of Fujian Medical University from January 2015 to September 2019. There were 10 males and 6 females, with age of (35.2±4.3)years (range, 22-59 years). According to the Schatzker fracture classification, type II was found in 10 patients, type III in 4, type V in 1 and type VI in 1. Two-column fractures were found in 14 patients and three-column fracture in 2 patients. All patients were treated by plate fixation through the extended Carlson approach. The anterior-posterior X-ray and 3D reconstruction CT scan test were taken at every 3 months after operation to assess fracture healing and posterior tilt angle of lateral tibial plateau. The Rasmussen knee function score was performed 12 months after operation. Complications were detected as well.Results:All patients were followed up for 13-38 months [(18.3±4.6)months]. All patients showed bone healing. At postoperative 12 months, the posterior tilt angle of lateral tibial plateau was reduced to (11.5±4.7)°, compared to preoperative (28.9±3.2)° ( P<0.05). At postoperative 12 months, the Rasmussen score was (25.8±1.1)points compared with preoperative (13.1±3.8)points ( P<0.05), and the results were excellent in 9 patients (56%), good in 6 (37%), and fair in 1 (6%), with the excellent-good rate of 94%. No complications were observed, such as skin necrosis, surgical site infection, internal fixator exposure or osteomyelitis. Conclusion:For tibial plateau fracture with combined posterolateral and anterolateral fragments, plate fixation via the extended Carlson approach is effective to reduce and fix the fracture, decrease the posterior tilt angle of lateral tibial plateau and improve the recovery of postoperative knee function, with no neurovascular injury complications.

Objective:To develop an air particulate protective mask filter test device that can simulate the dynamics process of human breathing.Methods:The new device used two air pumps working alternately to simulate the dynamics process of human breathing. On March 4th to 17th, 2017, the new device and the traditional one-way airflow mask filtration test device were used to measure the internal and external particle levels of 39 masks of 13 models of 6 brands, and then the filtration efficiency of the mask was calculated and the test results were compared.Results:For the mask without breathing valve, there was no statistically significant difference between the filter efficiency test results of the new device and the traditional unidirectional airflow filter performance test device ( P>0.05) . For masks with breathing valves, the new device detected that three of them had lower filtration efficiency (99.50% vs 98.63%, P<0.01) . After sealing the mask breathing valve with glue, the filtering efficiency of the mask with a breathing valve detected by the new device significantly improved (98.63% vs 99.50%, P<0.01) . Conclusion:This new device can simulate the dynamic process of human exhalation and inhalation, and measure the filtration efficiency of the mask. For masks with breathing valves, the new device makes it easier to detect the decrease in the filtering efficiency of the mask caused by the breathing valve.

Objective:To develop an air particulate protective mask filter test device that can simulate the dynamics process of human breathing.Methods:The new device used two air pumps working alternately to simulate the dynamics process of human breathing. On March 4th to 17th, 2017, the new device and the traditional one-way airflow mask filtration test device were used to measure the internal and external particle levels of 39 masks of 13 models of 6 brands, and then the filtration efficiency of the mask was calculated and the test results were compared.Results:For the mask without breathing valve, there was no statistically significant difference between the filter efficiency test results of the new device and the traditional unidirectional airflow filter performance test device ( P>0.05) . For masks with breathing valves, the new device detected that three of them had lower filtration efficiency (99.50% vs 98.63%, P<0.01) . After sealing the mask breathing valve with glue, the filtering efficiency of the mask with a breathing valve detected by the new device significantly improved (98.63% vs 99.50%, P<0.01) . Conclusion:This new device can simulate the dynamic process of human exhalation and inhalation, and measure the filtration efficiency of the mask. For masks with breathing valves, the new device makes it easier to detect the decrease in the filtering efficiency of the mask caused by the breathing valve.