The glucose metabolism is crucial for sustained brain activity as it provides energy and is a carbon source for multiple biomacromolecules; glucose metabolism decreases dramatically in Alzheimer’s disease (AD) and may be a fundamental cause for its development. Recent studies reveal that the alternative splicing events of certain genes effectively regulate several processes in glucose metabolism including insulin receptor, insulin-degrading enzyme, pyruvate kinase M, receptor for advanced glycation endproducts, and others, thereby, influencing glucose uptake, glycolysis, and advanced glycation end-products-mediated signaling pathways. Indeed, the discovery of aberrant alternative splicing that changes the proteomic diversity and protein activity in glucose metabolism has been pivotal in our understanding of AD development. In this review, we summarize the alternative splicing events of the glucose metabolism-related genes in AD pathology and highlight the crucial regulatory roles of splicing factors in the alternative splicing process. We also discuss the emerging therapeutic approaches for targeting splicing factors for AD treatment.

Objective To evaluate the efficacy and safety of suctioning flexible ureteroscopy with automatic control of renal pelvic pressure in the treament of intrarenal and proximal ureteral stones.Methods From November 2014 to December 2016,a total of 372 patients,including 200 males and 172 females,with upper urinary tract calculi were studied.The average age of patients was 48.1 years old.The average size of stone was 5-35mm,mean 15.7mm.There were 272 cases of renal calculi,80 cases of ureteral calculi and 20 cases of renal calculi combined with ureteral calculi.There were 252 cases of single calculi and 127 cases of multiple calculi.There were 237 cases of urinary tract infection and 14 cases of bacteremia.All patients were treated by suctioning fiexible uretemscopy with automatic control of renal pelvic pressure by a patented intelligent system including an irrigation and suctioning platform and a ureteral access sheath with a pressuresensitive tip.Statistical analysis was performed regarding renal pelvic pressure,operative time,stone-free rates,and complications.Results Three hundred and thirty of 372 patients only accepted one surgery to remove the stone.There were 12 cases of upper ureteral calculi were converted to ureteroscope lithotripsy.Seventeen cases were converted to percutaneous nephrolithotomy due to significant ureteral stenosis.Seven cases who failed the first surgery due to difficulty in placing the ureteral access sheath but flexible ureteroscopy were successfully performed in these patients after indwelling a D-J stent for 2 weeks.No stone was found in 6 cases,and the soft endoscope of ureter was examined.In all patients,the renal pelvic pressure of the pelvis was controlled within 20 mmHg.The average operative time was 15-180 min(mean 58.9 min).The stone-free rates was 95.55％ (322/337),the incidence of postoperative fever was 2.97％ (10/337),the sepsis rate was 1.19％ (4/337),the incidence of urinary sepsis was 0.89％ (3/337),the incidence of lumbago caused by extravasation was 0.59％ (2/337),and no peripheral viscera injury or death case.There was no statistically significant difference between preoperative and postoperative white and red blood cells (P ＞ 0.05).Conclusions This new type of suctioning flexible ureteroscopy with intelligent pressure-control has the advantages of perfusion attraction,pressure feedback,intelligent control and visualization of intracavity pressure.It could be a new type of operation with high safety,low complication and high stone free rate.

Objective:To explore the modification effect of physical activity on the genetic effects of type 2 diabetes mellitus (T2DM).Methods:The univariate moderation model was fitted to calculate the modifying effect of physical activity on the genetic effects of T2DM based on the data of 12 107 pairs of same gender twins aged 30 years and older enrolled by the Chinese National Twin Registry in 11 provinces/cities in China.Results:After adjusting for age and gender, the heritability of T2DM was 0.56 (0.31-0.84). Qualified physical activity could attenuate the genetic effects of T2DM. The heritability of T2DM in twin pairs with qualified physical activity was 0.46 (0.06-0.88), which was lower than that in twin pairs without qualified physical activity during the same model [0.68(0.36-0.94)].Conclusion:T2DM is a moderate genetic disease, physical activity can modify the genetic effects of T2DM.

Objective:To explore the gene-body mass index (BMI) interaction on coronary heart disease (CHD) in the Chinese adult twins.Methods:A total of 20 340 same-sex twin pairs registered in the Chinese National Twin Registry (CNTR) were enrolled in this study. Classical twin structure equation model was used to estimate the gene-BMI interaction on CHD.Results:After adjusting for age, we found that genetic variance of CHD differed as the function of BMI in male twins, which indicated the presence of a gene-BMI interaction on CHD ( P=0.008).The genetic moderating effect ( βa) was -0.14 (95% CI: -0.22--0.04), indicating that for each logarithmic transformation value of BMI increase, genetic path parameters would decrease by 0.14, which would result in the decrease of genetic variance of CHD. And the heritability of CHD was 0.77 (95% CI: 0.65-0.86) among the male twins with lower BMI (<24.0 kg/m 2), but 0.56 (95% CI: 0.33-0.74) among the male twins with high BMI (≥24.0 kg/m 2). However, there was no evidence suggesting that BMI could moderate genetic variants of CHD in female. Conclusion:We found a significant gene-BMI interaction on CHD in the Chinese male adult twins in China, and the heritability of CHD was higher among the twins whose BMI was <24.0 kg/m 2.

Objective:To analyze the heritability of coronary heart disease (CHD) among the Chinese twin adults.Methods:A total of 20 477 same-sex twin pairs aged 25 years and older from the Chinese National Twin Registry were interviewed. Structure equation model was used to estimate the heritability of CHD.Results:After adjusting for age and gender, the overall heritability of CHD was 0.75(0.68-0.81). Stratified analyses showed that genetic factors play a more important role in CHD incidence in ≥40 years or female twins. While the development of CHD was mainly influenced by environmental factors in 25-39 years or male twins.Conclusion:CHD is influenced by both genetic and environmental factors and the heritability is high.

Objective:To examine the heritability of body mass index (BMI) and coronary heart disease (CHD), and to explore whether genetic factors can explain their correlation.Methods:Participants were from 11 provinces/municipalities reqistered in the Chinese National Twin Registry (CNTR) from 2010 to 2018. Participants data were collected from face-to-face questionnaire survey. Bivariate structure equation model was used to estimate the heritability and the genetic correlation of BMI and CHD.Results:A total of 20 340 pairs of same-sex twins aged ≥25 years were included in this study. After adjusting for age and gender, the heritability of BMI and CHD was 0.52 (95% CI: 0.49-0.55) and 0.76 (95% CI: 0.69-0.81), respectively. Further, a genetic correlation was identified between BMI and CHD ( rA=0.10, 95% CI:0.02-0.17). Conclusion:In Chinese adult twin population, BMI and CHD are affected by genetic factors, and their correlation can be attributed to the common genetic basis.

Objective:To examine the heritability of body mass index (BMI) and coronary heart disease (CHD), and to explore whether genetic factors can explain their correlation.Methods:Participants were from 11 provinces/municipalities reqistered in the Chinese National Twin Registry (CNTR) from 2010 to 2018. Participants data were collected from face-to-face questionnaire survey. Bivariate structure equation model was used to estimate the heritability and the genetic correlation of BMI and CHD.Results:A total of 20 340 pairs of same-sex twins aged ≥25 years were included in this study. After adjusting for age and gender, the heritability of BMI and CHD was 0.52 (95% CI: 0.49-0.55) and 0.76 (95% CI: 0.69-0.81), respectively. Further, a genetic correlation was identified between BMI and CHD ( rA=0.10, 95% CI:0.02-0.17). Conclusion:In Chinese adult twin population, BMI and CHD are affected by genetic factors, and their correlation can be attributed to the common genetic basis.