Comparative analysis of the clinical features of nonvalvular atrial fibrillation among Tibetan, Han, and Hui patients in Qinghai Province, China.

BACKGROUND: Global nonvalvular AF rises, impacting health severely. In Qinghai, China's diverse setting, studying AF among varied ethnic groups is crucial OBJECTIVES: The purpose of this study was to compares cardiac features in AF among Tibetan, Han, and Hui patients to develop tailored prevention and treatment strategies for this region, the goal was to enhance the understanding of AF and provide an empirical basis for developing prevention and treatment strategies specific to this region METHODS: This study included a total of 3445 Tibetan, Han, and Hui patients diagnosed with nonvalvular atrial fibrillation and treated at the Qinghai Cardiovascular and Cerebrovascular Specialist Hospital, China, between January 2019 and January 2021. We analyzed the differences in cardiac structure, comorbidities, and other influencing factors among the different ethnic groups RESULTS: We found significant differences in gender, age, smoking history, lone atrial fibrillation, left heart failure, dilated cardiomyopathy, and diabetes between Tibetan, Han, and Hui patients (P < 0.05). Tibetan, Han, and Hui patients also differed with regard to left ventricular end-diastolic volume, left ventricular ejection fraction, fractional shortening, NT-proBNP, glycated hemoglobin, red blood cell distribution width, platelet count, platelet hematocrit, platelet distribution width, homocysteine (Hcy), C-reactive protein, and superoxide dismutase (SOD) (P < 0.05) CONCLUSION: Our study revealed variations in comorbidities, cardiac structure, and blood indexes among Tibetan, Han, and Hui AF patients, highlighting distinct patterns in complications and biomarker levels across ethnic groups.

The migration and differentiation of hUC-MSCs(CXCR4/GFP) encapsulated in BDNF/chitosan scaffolds for brain tissue engineering.

We previously developed a biomaterial scaffold that could effectively provide seed cells to a lesion cavity resulting from traumatic brain injury. However, we subsequently found that few transplanted human umbilical cord mesenchymal stem cells (hUC-MSCs) are able to migrate from the scaffold to the lesion boundary. Stromal derived-cell factor-1α and its receptor chemokine (C-X-C motif) receptor (CXCR)4 are chemotactic factors that control cell migration and stem cell recruitment to target areas. Given the low expression level of CXCR4 on the hUC-MSC membrane, lentiviral vectors were used to generate hUC-MSCs stably expressing CXCR4 fused to green fluorescent protein (GFP) (hUC-MSCs(CXCR4/GFP)). We constructed a scaffold in which recombinant human brain-derived neurotrophic factor (BDNF) was linked to chitosan scaffolds with the crosslinking agent genipin (CGB scaffold). The scaffold containing hUC-MSCs(CXCR4/GFP) was transplanted into the lesion cavity of a rat brain, providing exogenous hUC-MSCs to both lesion boundary and cavity. These results demonstrate a novel strategy for inducing tissue regeneration after traumatic brain injury.

Alu methylation serves as a biomarker for non-invasive diagnosis of glioma.

Current techniques for diagnosing glioma are invasive and do not accurately predict prognosis. We developed a novel, non-invasive liquid chip assay to diagnose glioma and predict prognosis. Using this method, we determined the methylation state of the Alu element in cell-free DNA extracted from the serum of 109 glioma patients. Controls included 56 patients with benign intracranial tumors and 50 healthy subjects. Matched tumor tissues were processed for 36 patients. The cfDNA from glioma patients showed lower levels of Alu methylation than the controls (P<0.01). Alu methylation was also lower in high-grade than low-grade gliomas (P<0.01), indicating that Alu methylation correlates negatively with disease severity. Moreover, Alu methylation correlated positively with survival (P<0.01). These findings suggest high-throughput liquid chip could serve as a non-invasive diagnostic assay for glioma.

An IDH1 mutation inhibits growth of glioma cells via GSH depletion and ROS generation.

The isocitrate dehydrogenase 1 (IDH1) gene mutation occurs frequently in glioma. While some studies have demonstrated that IDH1 mutations are associated with prolonged survival, the mechanism remains unclear. In this study, we found that growth was significantly inhibited in glioma cells overexpressing the mutated IDH1 gene. Furthermore, these cells were characterized by decreased intracellular NADPH levels accompanied by glutathione (GSH) depletion and reactive oxygen species (ROS) generation. Moreover, the increased apoptosis and the decreased proliferation were found in the glioma cells overexpressing the mutant IDH1 gene. Accordingly, our study demonstrates that using H2O2-regulated mutant IDH1 glioma cells could obviously increase the inhibition of cell growth; nevertheless, GSH had the opposite result. Our study provides direct evidence that mutation of IDH1 profoundly inhibits the growth of glioma cells, and we speculate that this is the major factor behind its association with prolonged survival in glioma. Finally, our study indicates that depletion of GSH and generation of ROS are the primary cellular events associated with this mutation.

PAX3 is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells.

Paired box 3 (PAX3) is overexpressed in glioma tissues compared to normal brain tissues, however, the pathogenic role of PAX3 in human glioma cells remains to be elucidated. In this study, we selected the human glioma cell lines U251, U87, SHG-44, and the normal human astrocytes, 1800, which have differential PAX3 expression depending upon the person. SiRNA targeting PAX3 and PAX3 overexpression vectors were transfected into U87 and SHG-44 glioma cell lines, and cell proliferation, invasion, apoptosis, and differentiation were examined by CCK-8 assays, transwell chamber assays, tunnel staining, Annexin V/PI analysis, and Western blotting, respectively. In addition, we used subcutaneous tumor models to study the effect of PAX3 on the growth of glioma cells in vivo. We found that PAX3 was upregulated in the three glioma cell lines. PAX3 knockdown inhibited cell proliferation and invasion, and induced apoptosis in the U87MG glioblastoma cell line, whereas PAX3 upregulation promoted proliferation, inhibited apoptosis, and increased invasion in the SHG-44 glioma cell line. Moreover, we found that targeting PAX3 expression in glioma cell lines together with chemotherapeutic treatment could increase glioma cell susceptibility to the drug. In subcutaneous tumor models in nude mice using glioma cell lines U-87MG and SHG-44, inhibition of PAX3 expression in glioblastoma U-87MG cells suppressed tumorigenicity, and upregulation of PAX3 expression in glioma SHG-44 cells promoted tumor formation in vivo. These results indicate that PAX3 in glioma is essential for gliomagenesis; thus, targeting PAX3 or its downstream targets may lead to novel therapies for this disease.

Detection of serum Alu element hypomethylation for the diagnosis and prognosis of glioma.

Global genomic hypomethylation is a hallmark of cancer in humans. In the present study, the feasibility of measuring hypomethylation of Alu elements (Alu) in serum and its clinical utility were investigated. Tumor tissues and matched serum specimens from 65 glioma patients and serum samples from 30 healthy controls were examined for Alu hypomethylation by bisulfite sequencing. The median serum Alu methylation level was 47.30 % in patients (interquartile range (IQR), 35.40-54.25 %) and 57.90 % in the controls (IQR, 55.25-61.45 %). The median Alu methylation level in tumor samples was 40.30 % (IQR, 36.80-54.20 %), which shows the correlation of Alu hypomethylation between tumor and serum samples (r = 0.882) in the study group. The methylation level was higher in the low-grade glioma group than in the high-grade group both in tumor and serum samples. A correlation between high methylation level and longer survival time was detected in tumor and serum samples. Receiver operating characteristic curve analysis showed that the area under the curve for diagnosis was 0.861 (95 % confidence interval, 0.789-0.933), suggesting that Alu hypomethylation in serum may be of diagnostic value. Our results indicate that the detection of Alu hypomethylation in serum may be clinically useful for the diagnosis and prognosis of glioma.