Methylation status and expression of TWEAK gene promoter region in peripheral blood of patients with rheumatoid arthritis / 北京大学学报(医学版)

OBJECTIVE@#To explore the relationship between tumor necrosis factor like weak inducer of apoptosis (TWEAK) gene and the pathogenesis of rheumatoid arthritis (RA) by detecting the DNA methylation level, mRNA expression level and serum protein concentration of TWEAK gene in peripheral blood.@*METHODS@#The MassARRAY method was used to detect the DNA methylation level of the TWEAK gene in the peripheral blood of 112 RA patients and 86 matched healthy volunteers. The real-time quantitative polymerase chain reaction method was used to detect the mRNA expression level of the TWEAK gene in the peripheral blood of the subjects. The enzyme-linked immunosorbent assay method was used to detect the serum TWEAK protein concentration of the subjects. The TWEAK gene DNA methylation level, mRNA expression level and serum protein concentration between the RA group and the healthy control group were compared, and the relationship between it and the degree of disease activity analyzed.@*RESULTS@#The overall DNA methylation level of TWEAK gene and the DNA methylation levels of CpG_11, CpG_17.18.19.20, CpG_40.41.42 site in the RA group were higher than those in the healthy control group (P=0.002, P=0.01, P=0.006, P=0.002, respectively). The DNA methylation level of CpG_55.56 site in the high disease activity group was higher than that in the medium and low disease activity group (P=0.041). The expression level of TWEAK gene mRNA in the peripheral blood of the RA group was lower than that of the healthy control group (P=0.023). The expression level of TWEAK gene mRNA in the high disease activity group was lower than that in the medium and low disease activity group (P=0.035). The serum TWEAK protein concentration of the RA group was not significantly different from that of the healthy control group (P=0.508), but it was positively correlated with the mRNA expression level (r=0.482, P < 0.001).@*CONCLUSION@#The TWEAK gene is closely related to the onset and progression of RA, and its hypermethylation state may be one of the epigenetic mechanisms regulating its low mRNA expression, and it can be used as one of the important indicators for clinical monitoring and evaluation of RA.

Observation and prevention of toxicity of super high dose of cyclophosphamide chemotherapy scheme for treating children with high risk neuroblastoma / 中华实用儿科临床杂志

Objective To observe a variety of the toxicity,and the incidence of super-high-dose cyclophosphamide as a main chemotherapy scheme for treating children with high risk neuroblastoma,and to summarize the prevention and cure of the disease.Methods The high risk neuroblastoma patients who were diagnosed in Hematologic Tumor of Beijing Children's Hospital Affiliated to Capital Medical University were selected.And they were received super high dose of cyclophosphamide mainly chemotherapy scheme-CAV (cyclophosphamide,adriamycin and vincristine) more than 2 courses according to BCH-NB-HR(Beijing Children's Hospital-Neuroblastoma-High Risk) scheme.Their clinical symptoms,signs,blood routine and blood biochemistry in 1-2-course of treatment were retrospectively analyzed and summarized.According to WHO anti-cancer drugs in acute and subacute toxicity reaction grading standards,the data were analyzed.Results There were 33 children consistent with the criterion of research,who received 66 times of super-high-dose cyclophosphamide as a main chemotherapy scheme.All of the patients had bone marrow suppression,granulocyte generated Ⅳ grade toxicity 56 (84.8％),white blood cell (＜ 1.0 × 109/L) Ⅳ grade toxicity was 56 (84.8％),and blood platelet(＜25 x 109/L) Ⅳ grade toxicity was 19(28.8％).Hemoglobin(＜65 g/L) Ⅳ grade toxicity was 4 (6.06％).The digestive system toxicity including nausea and vomiting toxicity (100.0％).Urogenital system toxicity:Hemorrhagic cystitis only was 1 (1.52％) ;Cardiac Ⅰ-Ⅲ grade toxicity was 3(4.55％).But skin and nervous system toxicity was not observed.No patients died from chemotherapy.Conclusions There is a high incidence of toxicity with super-high-dose of cyclophosphamide as a main chemotherapy scheme,and the highest incidence ineludes bone marrow suppression,digestive tract response and secondary infection.But side effects like hemorrhagic cys-titis,liver,kidney and cardiac toxicity are not significant.Super-high-dose cyclophosphamide chemotherapy scheme is clinically safe under the perfect supportive treatment and rigorous monitoring.