AMPK调节骨骼肌细胞GLUT4基因表达的机制研究

腺苷酸活化蛋白激酶(AMPK)能调节运动/肌肉收缩所引起的骨骼肌细胞葡萄糖转运蛋白4(GLUT4)基因的表达,但至今它的调节机制不清.研究显示在非运动刺激引起的细胞信号事件中由组蛋白去乙酰化酶(HDACs)以及组蛋白乙酰化酶(HATs)控制的组蛋白乙酰化状态是调节基因表达的重要机制,所以我们假设AMPK信号途径是通过征用HDACs中的HDAC5(在骨骼肌细胞内高表达)来实现对运动/肌肉收缩引起的GLUT4基因表达控制.细胞分为正常浓度葡萄糖对照组(NGLU组)、正常浓度AICAR组(NGLU AICAR组)、高浓度对照组(HGLU组)、高浓度AICAR组(HGLU AICAR组).用5 mmol/L和20 mmol/L葡萄糖浓度培养骨骼肌细胞后,NGLU AICAR组和HGLU AICAR组与肌肉收缩模拟信号刺激5-氨基-4-甲酰胺咪唑核糖核苷酸(AICAR)孵育.AICAR能激活NGLU组骨骼肌细胞AMPKα2、减少骨骼肌细胞核HDAC5蛋白、促使HDAC5与骨骼肌细胞加强因子(MEF2)蛋白分离和上调GLUT4基因的表达;相反,高浓度葡萄糖延迟由AICAR引起的AMPKα2磷酸化、AMPKα2向细胞核转入、HDAC5向细胞核转出和GLUT4基因的表达.实验结果说明在不同葡萄糖浓度下的骨骼肌细胞GLUT4基因表达变化都对应着上游AMPK蛋白和下游HDAC5蛋白的变化,AMPK可能是征用转录抑制子HDAC5来调节MEF2的活性而达到控制肌肉收缩所引起的GLUT4基因表达.     

Hyperuricemia as a risk factor of coronary heart disease: The Framingham Study

Uric acid values were obtained on subjects of the original Framingham cohort at their fourth and 13th biennial examinations. The mean uric acid value for men was 5.0 mg/dl at the fourth examination and 5.7 mg/dl at examination 13 and was 3.9 mg/dl and 4.7 mg/dl, respectively, for women. This secular trend was due to both "laboratory drift" and increasing use of diuretics. Serum uric acid values were consistently higher in subjects of both sexes who were taking antihypertensive drugs at both examinations. Serum uric acid values correlated with systolic and diastolic blood pressure in both sexes; the relationship was stronger in women than in men and for systolic than for diastolic pressure. Correlations were stronger at examination 4 than at examination 13 when more antihypertensive treatment was used. Examination 4 serum uric acid predicted the subsequent development of coronary heart disease, in general, and myocardial infarction, in particular, but not angina pectoris. The uric acid relationship with myocardial infarction was equally strong in both sexes, even correcting for antihypertensive treatment. However, in multivariate analysis, including age, systolic blood pressure, relative weight, cigarette smoking, and serum cholesterol, serum uric acid did not add independently to the prediction of coronary heart disease.     

Six-year follow-up afterHelicobacter pylori eradication in peptic ulcer disease

Background  

The longterm outlook afterHelicobacter pylori (H. pylori) eradication in peptic ulcer disease is unclear.     

A postdischarge venous thromboembolism risk calculator for inflammatory bowel disease surgery

BackgroundGuidelines recommend extended chemoprophylaxis for venous thromboembolism in high-risk patients having operations for inflammatory bowel disease. Quantifying patients' risk of venous thromboembolism, however, remains challenging. We sought (1) to identify factors associated with postdischarge venous thromboembolism in patients undergoing colorectal resection for inflammatory bowel disease and (2) to develop a postdischarge venous thromboembolism risk calculator to guide prescribing of extended chemoprophylaxis.MethodsPatients who underwent an operation for inflammatory bowel disease from 2012 to 2018 were identified from the American College of Surgeons National Surgical Quality Improvement Program for colectomy and proctectomy procedure targeted modules. Postdischarge venous thromboembolism included pulmonary embolism or deep vein thrombosis diagnosed after discharge from the index hospitalization. Multivariable logistic regression estimated the association of patient/operative factors with postdischarge venous thromboembolism. A postdischarge venous thromboembolism risk calculator was subsequently constructed.ResultsOf 18,990 patients, 199 (1.1%) developed a postdischarge venous thromboembolism within the first 30 postoperative days. Preoperative factors associated with postdischarge venous thromboembolism included body mass index (1.9% with body mass index ≥35 vs 0.8% with body mass index 18.5–24.9; odds ratio 2.34 [95% confidence interval 1.49–3.67]), steroid use (1.3% vs 0.7%; odds ratio 1.91 [95% confidence interval 1.37–2.66]), and ulcerative colitis (1.5% vs 0.8% with Crohn’s disease; odds ratio 1.76 [95% confidence interval 1.32–2.34]). Minimally invasive surgery was associated with postdischarge venous thromboembolism (1.2% vs 0.9% with open; odds ratio 1.42 [95% confidence interval 1.05–1.92]), as was anastomotic leak (2.8% vs 1.0%; odds ratio 2.24 [95% confidence interval 1.31–3.83]) and ileus (2.1% vs 0.9%; odds ratio 2.60 [95% confidence interval 1.91–3.54]). The predicted probability of postdischarge venous thromboembolism ranged from 0.2% to 14.3% based on individual risk factors.ConclusionPreoperative, intraoperative, and postoperative factors are associated with postdischarge venous thromboembolism after an operation for inflammatory bowel disease. A postdischarge venous thromboembolism risk calculator was developed which can be used to tailor extended venous thromboembolism chemoprophylaxis by individual risk.     

Relationship of pili to colonial morphology among pathogenic and nonpathogenic species of Neisseria.

Growth in colonies with type 1 morphology and the presence of pili are characteristics that have been associated with virulence of gonococci for humans. To determine whether the presence of pili per se might be responsible for colony type 1 morphology, the relationship of pili to colony type was examined in various species of Neisseria. Short pili (175 to 210 nm in length) were seen only on nonpathogenic neisseria, whereas long pili (up to 4,300 nm) were seen on organisms of both nonpathogenic and pathogenic species. Although long pili, similar to those found on organisms from high-domed, type 1 colonies of gonococci, were observed on organisms from high-domed, type 1 colonies of nonpathogenic Neisseria species, they were also observed on low-convex, type 4 colonies of meningococci and nonpathogenic neisseria. Among meningococci there was no difference in the morphology of colonies consisting of organisms with many long pili and colonies consisting of organisms that completely lacked pili. Thus, there was no consistent relationship of pili to colonial morphology. Unless the pili of N. gonorrhoeae are unique among Neisseria species in their influence on colonial morphology, it is likely that factors other than pili determine colony type 1 morphology of gonococci. Whether these same factors, either alone or in conjunction with pili, are also responsible for gonococcal virulence warrants further investigation.     

Prevalence of self-reported nutrition-related health problems in the Lower Mississippi Delta.

OBJECTIVES: The purpose of this study was to assess demographic and geographic differences in prevalence of self-reported nutrition-related health problems in Arkansas, Louisiana, and Mississippi. METHODS: The authors analyzed 1991 and 1993 Behavioral Risk Factor Surveillance System data for adults 18 years or older. RESULTS: Less educated African American women and women of other minority groups who were aged 35 to 64 years reported the highest prevalence of health problems. Geographic differences involved prevalence of hypertension, health status, and insurance status. CONCLUSIONS: Specific demographic subgroups and geographic areas with a high risk of health problems are in particular need of targeted interventions.     

Intra-anal intussusception: diagnosis by posteroanterior stress proctography

Intra-anal intussusception was diagnosed in eight of 39 patients on evacuation proctography. Posteroanterior views revealed prolapse of the infolded rectum into the anal canal on straining in seven of eight patients, associated with splaying open of the anal canal and sudden distal movement of the fold during prolapse. Similar changes were seen in four of 31 patients in whom intussusception had not been diagnosed on lateral evacuation proctography. The pattern of the collapsed rectum was assessed for fold length, thickness, and angulation in relation to the midline of the rectum. Infoldings that prolapsed were closer to the anorectal junction on stress (mean 14.6 42.4 mm, p < 0.0001) showed greater change in height between rest and strain (28.8 14.6 mm, p < 0.05) and became more acutely angled during straining (41.9 5.3°, p < 0.01). Intra-anal intussusception may be missed in 33% (four of 12 patients) on routine evacuation proctography. Posteroanterior stress proctography is a simple supplementary examination to validate intussusception.     

A twelve-year follow-up of preschool hyperactive children

Two percent (N = 21) of a large sample of preschool children were identified as "pervasively hyperactive." Compared with nonhyperactive preschoolers, these children more often came from families with high levels of adversity, and they showed poorer language skills. Over a 12-year follow-up period, the hyperactive preschoolers continued to show poorer cognitive skills, lower levels of reading ability, disruptive and inattentive behaviors at home and at school, and higher rates of DSM-III disorder in preadolescence and adolescence. By age 15, only one-quarter of this group were identified as having met "recovery" criteria. The findings point to the long-term adverse consequences of preschool hyperactivity and indicate the need for intervention with this type of disorder.