1.Clinical risk factors and cerebral magnetic resonance imaging characteristics of Tibetan newborns with hypoxic-ischemic encephalopathy in Lhasa, Tibet
Hong WU ; Rong ZHAO ; Minna SHAN ; Kanglu ZHAI
Chinese Journal of Neonatology 2019;34(1):20-23
Objective To study the clinical risk factors and the characteristics of cerebral magnetic resonance imaging (MRI) of hypoxic-ischemia encephalopathy (HIE) in full-term infants in high-altitude area.Method From January 2014 to December,2016 full-term Tibetan infants with HIE and healthy full-term Tibetan infants admitted to our hospital were enrolled in the study.General conditions and perinatal status were retrospectively analyzed.Univariate analysis and multivariate analysis were used to determine the risk factors of the HIE.MRI characteristics,location of the brain injuries and the correlation between HIE clinical grading and MRI grading were analyzed.Result During the study period,5 172 full-term Tibetan neonates were born in our hospital,198 of them were diagnosed of HIE and the incidence was 3.8%.According to HIE clinical grading,31 were mild,110 were moderate and 57 were severe.MRI grading included 34 mild,131 moderate and 33 severe.The main manifestations of MRI included white matter injury,especially subcortical white matter injury of frontal,parietal and occipital lobes,gray matter injury and diffuse cerebral edema.Mild HIE had a certain correlation with MRI grading,however,severe HIE had poor correlation with MRI grading.Multivariate Logistic regression analysis showed that abnormal birth weight (<2 500 g or>4 000 g) and intrauterine distress were independent risk factors of HIE in full-term Tibetan neonates[OR (95% CI):3.663 (1.961~6.843) and 5.419 (2.487~11.807)].Conclusion Macrosomia at birth,low birth weight and intrauterine distress are independent risk factors of HIE in Tibetan full-term neonates in Lhasa.White matter injury is the main MRI manifestation of HIE.Clinical grading of Mild HIE has good consistency with the MRI grading,but MRI grading is milder than the clinical grading for those with moderate and severe HIE.
2.Acetylated STAT3-induced DIRAS2 deletion promotes the proliferation of triple-negative breast cancer cells
Lifen ZHANG ; Lu WANG ; Lin ZHAO ; Minna LUO ; Shan SHAO ; Shanzhi GU
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(5):741-747
【Objective】 To explore the regulation of DIRAS2 gene expression by acetylated STAT3 and its involvement in the proliferation of triple-negative breast cancer (TNBC) cells. 【Methods】 The expression levels of DIRAS2 and acetylated STAT3 in TNBC tissues and cells were analyzed by database query, Western blotting, and qRT-PCR. TNBC cell lines MDA-MB-231 and SUM159 were selected, and lentivirus or plasmid was used to construct DIRAS2 overexpression and STAT3 wild or Lys685 mutation cell lines. The CCK-8 assay was used to evaluate the effect of DIRAS2 and STAT3 acetylation on the proliferation of TNBC cells. Western blotting, pyrosequencing, ChIP and IP were employed to investigate the regulatory effect and mechanism of acetylated STAT3 on DIRAS2 expression. 【Results】 The expression of DIRAS2 was decreased in TNBC tissues and cells. Pyrosequencing analysis found that the methylation level of CpG islands in the DIRAS2 promoter was increased in TNBC cells compared with normal breast epithelial cells, which promoted the growth of cancer cells. Furthermore, TNBC cells showed an increase in STAT3 acetylation, which was accompanied by a shift in the methylation status of the DIRAS2 promoter. ChIP and IP experiments showed that acetylated STAT3 could bind to the DIRAS2 promoter, and the STAT3 Lys685 mutation disrupted the interaction between STAT3 and DNMT1. 【Conclusion】 Acetylated STAT3 induces DIRAS2 promoter methylation by recruiting DNMT1, leading to loss of DIRAS2 expression and cancer cell proliferation in TNBC.