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Objective: To explore the genetic basis for a child with optic atrophy and global developmental delay., Methods: A child who had presented at the Guangzhou Women and Children's Medical Center in January 2022 was selected as the study subject. Clinical data were collected. Whole exome sequencing (WES) was carried out for the child. Candidate variant was validated by Sanger sequencing and bioinformatic analysis., Results: The child, a nine-month-old female, had manifested dysopia and global developmental delay. Genetic testing revealed that she has harbored a de novo c.425G>C (p.Arg142Pro) variant of the NR2F1 gene, which has been associated with Bosch-Boonstra-Schaaf syndrome. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS2+PM1+PM2_Supporting+PM5+PP3+PP4)., Conclusion: The c.425G>C (p.Arg142Pro) variant of the NR2F1 gene probably underlay the pathogenesis in this child. Above finding has enriched the genotypic and phenotypic spectrum of the NR2F1 gene.

Objective: To explore the genetic basis for a child featuring global developmental disorder with epilepsy., Methods: A child who had presented at Guangzhou Women and Children's Medical Center in July 2022 was selected as the study subject. Clinical data was collected. Potential variant was detected by whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing and bioinformatic analysis., Results: The child, a three-year-old ethnic Zhuang Chinese girl, had presented with global developmental disorder and epilepsy, for which rehabilitation therapy was ineffective. Genetic testing revealed that she has harbored a homozygous c.821T>C (p.Leu274Pro) missense variant of the PIGW gene, for which both of her parents and sister were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as variant of uncertain significance., Conclusion: The homozygous c.821T>C (p.Leu274Pro) variant of the PIGW gene probably underlay the onset of disease in this child. Above finding has enriched the mutational spectrum of the PIGW gene.

Objective: Proteolytic enzymes possibly contribute to coronary artery ectasia (CAE). This study aimed to determine whether neutrophils, neutrophil serine proteases (NSPs), and their endogenous inhibitors participated in the pathological process of CAE., Methods: The study consisted of 30 patients with CAE, 30 patients with coronary artery disease (CAD), and 29 subjects with normal coronary arteries (Control). The following circulating items were measured: the main NSPs, including human neutrophil elastase (HNE), cathepsin G (CG), and proteinase 3 (PR3); soluble elastin (sElastin), which was a degradation product of elastin fibres; NSP inhibitors such as α1-protease inhibitor (α1-PI), α2-macroglobulin (α2-MG), secretory leucoprotease inhibitor (SLPI), and elafin; as well as two neutrophil activation markers (myeloperoxidase and lactoferrin) and three classic neutrophil activators [tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and bacterial endotoxin]., Results: The levels of HNE, CG, and sElastin were elevated in the CAE group. The levels of α1-PI and α2-MG were also significantly increased in the CAE group. The levels of myeloperoxidase and lactoferrin were higher in the CAE group. The levels of TNF-α, IL-8, and endotoxin were unchanged in the CAE group compared with those in the CAD group., Conclusion: Neutrophils may participate in the process of vessel extracellular matrix destruction and coronary ectasia by releasing NSPs in a non-classical manner.

Objective: To evaluation the prevalence of hypertension, diabetes, dyslipidemia in systemic lupus erythematosus (SLE) patients, and investigate the factors that affecting lipid levels in SLE patients., Methods: A total of 540 adult SLE patients hospitalized in Peking Union Medical College Hospital from March 2010 to March 2013 were retrospectively included (SLE group), and 1 080 gender and age matched (1: 2) healthy controls were selected from our medical examination center (control group). The prevalence rate of hypertension, diabetes, dyslipidemia and the levels of serum lipid were compared between the two groups, the factors affecting lipid levels in SLE patients were also analyzed., Results: The percentage of hypertension, diabetes, dyslipidemia, elevated total cholesterol (TC), elevated triglyceride (TG), decreased high density lipoprotein cholesterol (HDL-C) and elevated low density lipoprotein cholesterol (LDL-C) in SLE patients were significantly higher than those in healthy controls (all P < 0.01) . Compared with the control group, SLE patients had significantly higher TC, TG, LDL-C levels and significantly lower HDL-C levels (all P < 0.01) . Multifactor regression analysis showed that TC and LDL-C levels were positively correlated with lupus nephritis (β = 0.695,0.437), corticosteroids therapy (β = 1.195, 0.715), complement C4 levels (β = 4.817, 3.382) and 24 hours urine protein content (β = 0.112, 0.078) (all P < 0.01) , but negatively correlated with serum albumin (Alb) (β = -0.107, -0.077) and high sensitive C reactive protein (hsCRP) levels (β = -0.021, -0.014) (all P < 0.01). TG levels were positively correlated with lupus nephritis (β = 0.359) and 24 hours urine protein content (β = 0.045) (both P < 0.05), negatively correlated with male gender (β = -0.605), age (β = -0.014) and Alb levels (β = -0.053) (P < 0.01 or 0.05). HDL-C levels were positively correlated with age (β = 0.007), lupus nephritis (β = 0.188), corticosteroids therapy (β = 0.342), consecutive 30 days cumulative corticosteroids dose before serum lipid were measured (β<0.001), and complement C3 levels(β = 0.351) (all P < 0.01) , negatively correlated with hsCRP levels (β = -0.005, P < 0.01). Serum lipid levels did not correlate with disease duration, disease activity, corticosteroids therapy time, corticosteroids daily dose before serum lipid measurement, serum creatinine levels and erythrocyte sedimentation rate (ESR) (all P > 0.05)., Conclusion: The prevalence rate of hypertension, diabetes and dyslipidemia in SLE hospitalized patients are significantly higher compared to normal controls and lipid levels of SLE patients are related to various SLE disease factors.

Objective: To analyze the changes of gene expression profiles during the process that human bone marrow mesenchymal stem cells (hBMSCs) are induced to differentiate into cardiomyogenic cells with 5-azacytidine (5-aza)., Methods: hBMSCs were isolated from marrow of obsolete ribs and induced with 5-aza. Then immunocytochemical staining was used to detect the expressions of alpha-actin, cardiac troponin T (cTnT), and connexin 43, and the percentage of cTnT positive cells was tested with flow cytometry. In the process of differentiation, variation of gene expression was screened with Genechips Operating System of human gene expression profiles. And the differentially expressed genes were functionally analyzed and hierarchical clustered., Results: When BMSCs were induced in vitro with 5-aza, part of the cells turned into myogenic cells morphologically. Before induction, immunocytochemical staining for alpha-actin and cTnT showed slight positive and for connexin 43 showed negative. While after 3 weeks of induction, immunocytochemical staining for alpha-actin, cTnT, and connexin 43 showed all positive. With flow cytometry, the percentage of cTnT positive cells was 7.43% +/- 0.02% before induction, but it was 49.64% +/- 0.05% after induction. During differentiation, 1 814 differentially expressed genes were reported by gene chips. Of them, 647 genes were divided into 5 groups with hierarchical clustering. They had various biological functions, involving signal transduction, cell metabolism, proliferation, differentiation, development, and topogenesis., Conclusion: hBMSCs can differentiate into cardiomyogenic cells with the induction of 5-aza in vitro. Multiple genes related with signal transduction, transcription, and growth factors are involved during this process.