目的分析总结青少年起病的成人型糖尿病2型(maturity-onset diabetes of the young type 2,MODY2)患儿的临床表现及遗传学特点,提高临床工作中对MODY2的识别能力。方法回顾性分析2017年8月—2023年7月在华中科技大学同济医学院附属同济...目的分析总结青少年起病的成人型糖尿病2型(maturity-onset diabetes of the young type 2,MODY2)患儿的临床表现及遗传学特点,提高临床工作中对MODY2的识别能力。方法回顾性分析2017年8月—2023年7月在华中科技大学同济医学院附属同济医院儿科确诊的13例MODY2患儿的临床资料。结果13例MODY2患儿(编号P1~13)均有糖尿病家族史,均为健康体检或因感染性疾病偶然发现的轻度空腹高血糖[(6.4±0.5)mmol/L)]。其中2例空腹血糖达到糖尿病诊断标准,其他病例均为空腹血糖受损或糖耐量受损;1 h血糖(one-hour post-glucose,1-hPG)波动在8.31~13.06 mmol/L,已到达国际糖尿病联盟推荐的糖尿病诊断标准。13例MODY2患儿均为葡萄糖激酶(glucokinase,GCK)基因杂合变异,其中P6为GCK c.1047C>A(p.Y349X)、P11为GCK c.1146_1147insGCAGAGCGTGTCTACGCGCGCTGCGCACATGTGC(p.S383Alafs*87)和P13为GCK c.784_785insC(p.D262Alafs*13),均为尚未报道过的变异。结论该研究丰富了MODY2的基因变异谱;临床对于有糖尿病家族史、偶然发现的轻度空腹血糖增高、糖尿病相关抗体阴性的患儿,需警惕MODY2可能。展开更多
Objective To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.Methods Twenty male SD rats were ra...Objective To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.Methods Twenty male SD rats were randomized equally into control group and heat stress group.After exposure to 32℃for 2 weeks in the latter group,the rats were examined for histopathological changes and Bmal1 expression in the thoracic aorta using HE staining and immunohistochemistry.In the cell experiments,cultured rat thoracic aortic endothelial cells(RTAECs)were incubated at 40℃for 12 h with or without prior transfection with a Bmal1-specific small interfering RNA(si-Bmal1)or a negative sequence.In both rat thoracic aorta and RTAECs,the expressions of Bmal1,the cell cycle proteins CDK1,CDK4,CDK6,and cyclin B1,and apoptosis-related proteins Bax and Bcl-2 were detected using Western blotting.TUNEL staining was used to detect cell apoptosis in rat thoracic aorta,and the changes in cell cycle distribution and apoptosis in RTAECs were analyzed with flow cytometry.Results Compared with the control rats,the rats exposed to heat stress showed significantly increased blood pressures and lowered heart rate with elastic fiber disruption and increased expressions of Bmal1,cyclin B1 and CDK1 in the thoracic aorta(P<0.05).In cultured RTAECs,heat stress caused significant increase of Bmal1,cyclin B1 and CDK1 protein expression levels,which were obviously lowered in cells with prior si-Bmal1 transfection.Bmal1 knockdown also inhibited heat stress-induced increase of apoptosis in RTAECs as evidenced by decreased expression of Bax and increased expression of Bcl-2.Conclusion Heat stress upregulates Bmal1 expression and causes alterations in expressions of cyclins to trigger apoptosis of rat thoracic aorta endothelial cells,which can be partly alleviated by suppressing Bmal1 expression.展开更多
文摘目的分析总结青少年起病的成人型糖尿病2型(maturity-onset diabetes of the young type 2,MODY2)患儿的临床表现及遗传学特点,提高临床工作中对MODY2的识别能力。方法回顾性分析2017年8月—2023年7月在华中科技大学同济医学院附属同济医院儿科确诊的13例MODY2患儿的临床资料。结果13例MODY2患儿(编号P1~13)均有糖尿病家族史,均为健康体检或因感染性疾病偶然发现的轻度空腹高血糖[(6.4±0.5)mmol/L)]。其中2例空腹血糖达到糖尿病诊断标准,其他病例均为空腹血糖受损或糖耐量受损;1 h血糖(one-hour post-glucose,1-hPG)波动在8.31~13.06 mmol/L,已到达国际糖尿病联盟推荐的糖尿病诊断标准。13例MODY2患儿均为葡萄糖激酶(glucokinase,GCK)基因杂合变异,其中P6为GCK c.1047C>A(p.Y349X)、P11为GCK c.1146_1147insGCAGAGCGTGTCTACGCGCGCTGCGCACATGTGC(p.S383Alafs*87)和P13为GCK c.784_785insC(p.D262Alafs*13),均为尚未报道过的变异。结论该研究丰富了MODY2的基因变异谱;临床对于有糖尿病家族史、偶然发现的轻度空腹血糖增高、糖尿病相关抗体阴性的患儿,需警惕MODY2可能。
文摘Objective To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.Methods Twenty male SD rats were randomized equally into control group and heat stress group.After exposure to 32℃for 2 weeks in the latter group,the rats were examined for histopathological changes and Bmal1 expression in the thoracic aorta using HE staining and immunohistochemistry.In the cell experiments,cultured rat thoracic aortic endothelial cells(RTAECs)were incubated at 40℃for 12 h with or without prior transfection with a Bmal1-specific small interfering RNA(si-Bmal1)or a negative sequence.In both rat thoracic aorta and RTAECs,the expressions of Bmal1,the cell cycle proteins CDK1,CDK4,CDK6,and cyclin B1,and apoptosis-related proteins Bax and Bcl-2 were detected using Western blotting.TUNEL staining was used to detect cell apoptosis in rat thoracic aorta,and the changes in cell cycle distribution and apoptosis in RTAECs were analyzed with flow cytometry.Results Compared with the control rats,the rats exposed to heat stress showed significantly increased blood pressures and lowered heart rate with elastic fiber disruption and increased expressions of Bmal1,cyclin B1 and CDK1 in the thoracic aorta(P<0.05).In cultured RTAECs,heat stress caused significant increase of Bmal1,cyclin B1 and CDK1 protein expression levels,which were obviously lowered in cells with prior si-Bmal1 transfection.Bmal1 knockdown also inhibited heat stress-induced increase of apoptosis in RTAECs as evidenced by decreased expression of Bax and increased expression of Bcl-2.Conclusion Heat stress upregulates Bmal1 expression and causes alterations in expressions of cyclins to trigger apoptosis of rat thoracic aorta endothelial cells,which can be partly alleviated by suppressing Bmal1 expression.
