Correlation between fasting plasma glucose, HbA1c and DNA methylation in adult twins / 北京大学学报(医学版)

OBJECTIVE@#To explore the cytidine-phosphate-guanosine (CPG) sites associated with fas-ting plasma glucose (FPG) and glycated haemoglobin (HbA1c) in twins.@*METHODS@#In the study, 169 pairs of monozygotic twins were recruited in Qingdao, Zhejiang, Jiangsu, Sichuan and Heilongjiang in June to December of 2013 and June 2017 to October 2018. The methylation was detected by Illumina Infinium HumanMethylation450 BeadChip and Illumina Infinium MethylationEPIC BeadChip. According to the Linear Mixed Effect model (LME model), fasting plasma glucose and HbA1c were taken as the main effects, the methylation level (β value) was taken as the dependent variable, continuous variables, such as age, body mass index (BMI), blood pressure, components of blood cells, surrogate variables generated by SVA, and categorical variables, such as gender, smoking and drinking status, hypoglycemic drugs taking, were included in the fixed effect model as covariates, and the identity numbers (ID) of the twins was included in the random effect model. The intercept was set as a random. Regression analysis was carried out to find out the CpG sites related to fasting blood glucose or HbA1c, respectively.@*RESULTS@#In this study, 338 monozygotic twins (169 pairs) were included, with 412 459 CpG loci. Among them, 114 pairs were male, and 55 pairs were female, with an average age of (48.2±11.9) years. After adjustment of age, gender, BMI, blood pressure, smoking, drinking, blood cell composition, and other covariates, and multiple comparison test, 7 CpG sites (cg19693031, cg01538969, cg08501915, cg04816311, ch.8.1820050F, cg06721411, cg26608667) were found related to fasting blood glucose, 3 of which (cg08501915, ch.8.1820050f, cg26608667) were the newly found sites in this study; whereas 10 CpG sites (cg19693031, cg04816311, cg01538969, cg01339781, cg01676795, cg24667115, cg09029192, cg20697417, ch.4.1528651F, cg16097041) were found related to HbA1c, and 4 of which(cg01339781, cg24667115, cg20697417, and ch.4.1528651f) were new. We found that cg19693031 in TXNIP gene was the lowest P-value site in the association analysis between DNA methylation and fas-ting plasma glucose and HbA1c (PFPG=2.42×10-19, FDRFPG<0.001; PHbA1c=1.72×10-19, FDRHbA1c<0.001).@*CONCLUSION@#In this twin study, we found new CpG sites related to fasting blood glucose and HbA1c, and provided some clues that partly revealed the potential mechanism of blood glucose metabolism in terms of DNA methylation, but it needed further verification in external larger samples.

Clinical observation on muscle regions of meridians needling method in improving upper limb function for children with cerebral palsy of spastic hemiplegia type / 针灸推拿医学（英文版）

Objective: To observe the improving effect of muscle regions of meridians needling method on the upper limb function in children with cerebral palsy of spastic hemiplegic type. Methods: A total of 100 children with cerebral palsy of spastic hemiplegia type were divided into a treatment group and a control group according to the visiting sequence, with 50 cases in each group. The control group was treated with conventional rehabilitation plus conventional acupuncture treatment. The treatment group was treated with conventional rehabilitation plus muscle regions of meridians needling method. The electromyography (EMG) signal values of triceps brachii and pronator teres were detected before treatment, and 3 months and 6 months after treatment. The clinical efficacy was evaluated by Peabody developmental motor scale-fine motor (PDMS-FM) and fine motor function measure (FMFM). Results: Three and six months after treatment, the EMG signal values of triceps brachii and pronator teres, grasping scores and visual-motor integrated scores of PDMS-FM and the FMFM scores in both groups increased to varying degrees compared with the same group before treatment, and the intra-group differences were all statistically significant (all P<0.05). Six months after treatment, the results of the above three items in the treatment group were all better than those in the control group, and the differences between the groups were statistically significant (all P<0.05). Conclusion: Muscle regions of meridians needling method added on the basis of conventional rehabilitation can effectively reduce the muscle tone of upper limb and enhance the muscle strength, and improve the upper limb function in children with cerebral palsy of spastic hemiplegia type. The efficacy is superior to that of the conventional rehabilitation plus conventional acupuncture treatment.

Analysis of the incidence and mortality trend of breast cancer in Chinese women from 2005 to 2013 / 中华疾病控制杂志

@# Objective To Analyze the change trend of the incidence and mortality of breast cancer in Chinese women from 2005 to 2013 in the Chinese Cancer Registry Annual Report in order to provide references for the implement of the prophylaxis and treatment of breast cancer. Methods Extracted all the records of the incidence and mortality of breast cancer in Chinese women from 2005 to 2013, applied the Joinpoint regression model to analyze the change trend of the incidence and mortality of breast cancer in Chinese women. Results The incidence levels of breast cancer among urban women in China was higher than that in rural from 2005 to 2013, the change trend of urban incidence was stable(t=-0.2, P=0.828), the rural incidence showed an increasing trend(t=7.8, P<0.001). The peaks of urban and rural incidence were in the age group of 50- and the age group of 45- respectively.The mortality of breast cancer among urban women in China was higher than that in rural from 2005 to 2013, the change trend of urban mortality was stable(t=0.8, P=0.458), and the rising trend of rural mortality was obvious(t=3.3, P=0.014). The mortality of urban women began to rise after the age of 30, accelerating to rise after the age of 75, the mortality of rural women began to rise after the age of 30, the change tended to be stable at the age of 55-69, and began to rise after the age of 70 again. Conclusions The incidence and mortality of breast cancer among urban women in China were all higher than that in rural from 2005 to 2013, the rising trend of the incidence and mortality of breast cancer among rural women was obvious, so the prophylaxis and treatment measures of breast cancer should be actively formulated and perfected.

Correlation between blood pressure and DNA methylation in adult twins / 北京大学学报(医学版)

OBJECTIVE@#To explore the DNA methylation sites correlated with blood pressure (systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse pressure) in adult twin population.@*METHODS@#A total of 476 twins from the Chinese National Twin Registry were selected as the research population. Questionnaires were used to collect demographic characteristics, lifestyle, disease status and other information, and blood pressure, height, weight and other anthropometric indicators were measured. The genome-wide DNA methylation of whole blood samples was detected by using Infinium HumanMethylation450 BeadChip. The DNA methylation sites correlated with blood pressure were analyzed by constructing mixed effect model with adjusting potential confounding factors, and the significant level was false discovery rate <0.05.@*RESULTS@#After data quality control, 465 twins (122 pairs of monozygotic twins, 104 pairs of dizygotic twins, 13 individuals from 13 pairs of twins) aged (44.8±13.2) years were finally enrolled. There were more males and more monozygotic twins, and the current smokers and current regular drinkers both accounted for more than 30%. No significant CpG site was found after multiple testing in the correlation study between genome-wide DNA methylation and blood pressure by using the collected twins. However, the cg07761116 located on chromosome 10 had low P value in the correlation analysis of 3 blood pressure indices (systolic blood pressure, diastolic blood pressure, mean arterial pressure), suggesting that this site might be correlated with blood pressure. The other 7 sites had low P value in the correlation analysis of the two blood pressure indices, respectively, which pointed to genes involved in neurological development, protein homeostasis, inflammatory reaction and other pathways.@*CONCLUSION@#There is no sufficient evidence to support any DNA methylation site correlated with blood pressure, which may be caused by insufficient sample size and other reasons. This study could provide a reference for subsequent similar twin studies, and subsequent studies can focus on the cg07761116 located on chromosome 10 and other sites with low P values.

Stroke following off-pump coronary artery bypass grafting in patients with prior stroke / 中华胸心血管外科杂志

Objective To analyze the risk factors and clinical features of stroke following off-pump coronary artery bypass grafting in patients with prior stroke. Methods From January 2006 to July 2009, the clinical information of 437 patients undergoing OPCABC in Anzhen Hospital was collected. The patients were divided into stroke group and non-stroke group according to whether stroke occurred after operation. Preoperative and operative variants were evaluated by univariate and multivariate logistic stepwise regression analysis. Results 32 of 437 patients (7.3% ) suffered from stroke after OPCABG, 32 cases were cerebral infarction and no case was cerebral hemorrhage. There were more patients whose left ventricular ejection fraction ≤0. 50 in stroke group than that in non-stroke group (12 of 32, 37.5% versus 69 of 405, 17.0% , P = 0. 004), more patients had atrial fibrillation after operation in stroke group than that in non-stroke group (9 of 32, 28. 1% versus 27 of 405,6.7% , P ＜ 0.001), more patients had hypotension after operation in stroke group than that in non-stroke group (13 of 32,40.6% versus 42 of 405, 10. 4% ; P ＜ 0. 001), more patients had ventilatory time and ICU time after operation in stroke group than that in non-stroke group(9 of 32, 28.1% versus 49 of 405, 12.1% , P =0.021; 14of 32,43.8% versus 97 of 405, 24.0% , P = 0.013), and patients in stroke group took longer to stay in hospital than that in non-stroke group (29.0 ±15. 8 versus 22. 9 ± 10. 4, P = 0. 002 ). Logistic stepwise regression analysis showed that left ventricular ejection fraction SS0.50(OR=2.837, 95%CI: 1.238-6.498), atrial fibrillation after operation( OR =3. 065, 95% CI: 1.157-8.118) and hypotension after operation (OR =4.209, 95%CI: 1.805 -9. 813) were independent risk factors of stroke following offpump coronary artery bypass grafting in patients with prior stroke. Conclusion This data suggest that left ventricular ejection fraction ≤0. 50, atrial fibrillation and hypotension after operation are risk factors for stroke following off-pump coronary artery bypass grafting in patients with prior stroke. These patients with stroke after operation took longer to extubate and stay in ICU and hospital.

The changes in the mRNA levels of calcium regulatory proteins in ischemia/reperfusion rat ventricles / 中国应用生理学杂志

<p><b>AIM</b>To investigate the changes in the expression of four kinds of calcium regulatory proteins mRNA on the isolated ischemia/ reperfusion (IR) hearts.</p><p><b>METHODS</b>The rat hearts were divided into two groups: control group and IR group which received 45 min exposure to Krebs-Henseleit solution after 15 min zero-flow global ischemia. The indexes of left ventricular function, such as LVDP, +dp/dt(max), -dp/dt(max), and an arrhythmia scoring system were compared between the two groups. The messenger ribonucleic acid (mRNA) amount of sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA), phospholamban (PLB), inositol 1,4,5-trisphosphate receptor2 (IP3R2) and ryanodine receptor2 (RyR2) was measured by reverse transcription-polymerase chain reaction (RT-PCR) and normalized to the mRNA levels of beta-actin.</p><p><b>RESULTS</b>In the IR group, LVDP, +dp/dt(max) and -dp/dt(min) of the isolated hearts were depressed and the high rate of arrhythmias occurred during reperfusion. The levels of SERCA, IP3R2, RyR2 mRNA were lower in the IR isolated hearts group than those in the control group, while there was no difference in the level of phospholamban.</p><p><b>CONCLUSION</b>These data suggest that myocardial ischemia/reperfusion can induce the depression of cardiac performance and an increased risk of arrhythmias, concomitant with the decrease in SERCA, IP3R2, RyR2 mRNA steady state levels.</p>

Relaxant effect of Astragalus membranaceus on smooth muscle cells of rat thoracic aorta / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of Astragalus membranaceus(AM) on vascular circles and the underlying mechanisms.</p><p><b>METHODS</b>The study was performed with the model of isolate rat thoracic aorta rings in organ bath. When the endothelium of rat thoracic aorta was removed,the effect of accumulated AM on aorta rings in resting tension, or pre-constricted with KCl, or pre-constricted with phenylephrine (PE) was observed. And to explove the mechanism, the aorta rings were incubated with Ca(2+)-free medium alone, or Ca(2+)-free medium plus heparin, or propranolol alone before pre-contraction with PE.</p><p><b>RESULTS</b>AM had no significant effects on aorta rings in resting tension or pre-constricted with KCl. When the concentration of AM was cumulated to 10(-1), 3 x 10(-1),10(0), 3 x 10(0) g/L, it caused concentration-dependent relaxation while aorta rings were pre-constricted with PE(3 x 10(-7)mol/L), compared with the control [(90.4 +/-4.2)% compared with (94.7 +/-2.4)%,(86.1 +/-5.0)% compared with (92.6 +/-3.2)%, (82.3 +/-5.9)% compared with (90.4 +/-3.6) %, (78.3 +/-6.0)% compared with (88.1 +/-4.0)%]. This effect was not inhibited by Ca(2+)-free medium or propranolol alone. However, the effect was attenuated by the co-incubation with heparin and Ca(2+)-free medium [without heparin:(76.2+/-4.3)% compared with (92.3 +/-5.9)%, with heparin: (95.3+/-0.5)% compared with (95.1+/-0.6)%].</p><p><b>CONCLUSION</b>The results indicate that AM can relax the rat thoracic aorta rings without endothelium. The mechanism may include the inhibition of intracellular calcium ions release by the 1,4,5-triphosphate inositol-receptor-dependent pathway in vascular smooth muscle cells.</p>