Change of cardiovascular risk associated serologic biomarkers after gastric bypass: A comparison of diabetic and non-diabetic Asian patients

BackgroundWhile clinical findings demonstrate a superior benefit of cardiovascular (CV) risk reduction in obese patients with type 2 diabetes mellitus (T2D) receiving bariatric surgery over non-T2D patients, the mechanism is unclear. This study aimed to investigate the changes in the CV risk score and five CV-associated biomarkers after gastric bypass surgery.MethodWe enrolled 80 obese subjects who underwent gastric bypass (40 T2D and 40 non-T2D). CV risks were assessed using the United Kingdom Prospective Diabetes Study (UKPDS) engine before and after surgery. Levels of five biomarkers —fasting serum fibroblast growth factor (FGF)-19, FGF-21, corin, oxidized low-density lipoprotein (ox-LDL), and soluble receptor for advanced glycation end-products (sRAGE)—were measured before surgery and one year after surgery.ResultsThe T2D group was significantly older and had a higher CV risk score than the non-T2D group, but body mass index (BMI) was similar between the groups. Preoperative biomarker levels were similar in both the T2D and the non-T2D groups. One year after surgery, the percentage of total weight loss (%TWL) was similar between the two groups (32.2 ± 19.5% versus 34.1% ± 8.8%, p = 0.611). Complete T2D remission (hemoglobin A1c (HbA1c) < 6.0%) was achieved in 29 patients (72.5%). The 10-year CV risk scores by the UKPDS risk engine reduced significantly in both the T2D and the non-T2D groups, but more in the T2D group. Three of five biomarkers changed significantly after surgery: the FGF-19 increased from 195.6 ± 249.1 pg/mL to 283.2 ± 211.8 pg/mL, corin increased from 3.3 ± 2.3 ng/mL to 4.6 ± 3.7 ng/mL, and ox-LDL decreased from 148.5 ± 71.7–107.9 U/L; the P values were 0.002, 0.002 and < 0.001, respectively. The T2D group showed a significantly different change in FGF-19 increase and FGF-21 decrease compared to the non-T2D group. The changes in corin and ox-LDL levels were not different between the T2D and non-T2D groups.ConclusionGastric bypass surgery resulted in a higher UKPDS CV risk score reduction in obese T2D Asians than in those without. FGF-19 and FGF-21 may be associated with the underlying mechanism of this difference.     

Femoral neck narrowing after metal-on-metal hip resurfacing

We reviewed 40 Corin Cormet 2000 (Corin, Cirencester, UK) metal-on-metal resurfacing hips, in 36 patients, for the presence of femoral neck narrowing. A neck-to-prosthesis ratio was calculated by dividing the diameter of the femoral neck with that of the implant. This ratio was measured on plain anteroposterior pelvis radiographs taken immediately and 2 years postoperation. Subsequent radiographs were measured up to a maximum 7 years (mean, 5.3 years) postoperation. Femoral neck narrowing was observed in 90% of hips at 2 years, with the average neck narrowing ranging from a ratio of 0.865 to 0.811. Importantly, no further narrowing occurred beyond this point up to 7 years postoperation. We described a simple reproducible method of measuring neck narrowing on plain radiographs and discuss possible causal factors for neck narrowing after hip resurfacing.     

Long term results of the Corin C-Fit uncemented total hip arthroplasty in young patients

Introduction  We conducted a prospective study to evaluate the long-term results after Corin C-Fit uncemented total hip arthroplasty in young patients with hydroxyapatite or porous coated components. Materials and methods  We prospectively followed 36 patients (38 hips) who had Corin C-Fit uncemented total hip arthroplasties by eight experienced consultant surgeons at two centres. The acetabular and femoral components were hydroxyapatite or porous coated. Results  The overall 10-year survival rate for the Corin C-Fit arthroplasty was 43%. The 10-year survivorship for the femoral implant was 56% and for the acetabular component 59%. Conclusion  The evidence presented in this study suggests that the Corin C-Fit uncemented total hip arthroplasty has one of the highest mid- and long-term failure rates for both femoral and acetabular components in the literature. We believe this implant should not be used and patients who have had this form of total hip arthroplasty should be kept under regular review.     

蛋白酶Corin在高血压发病中的作用

丝氨酸蛋白酶Corin主要表达于心脏,可将无活性的心房利钠肽前体（pro-atrial natriuretic peptide,pro-ANP）和脑钠肽前体（pro-brain natriuretic peptide,pro-BNP）转化为有活性的心房利钠肽（ANP）和脑钠肽（BNP）,从而发挥排钠利尿、舒张血管、降低血压和改善心功能的作用。除心脏以外,Corin还表达于妊娠子宫、肾脏及骨骼等组织器官,参与机体的多种生理过程。近年来研究发现,Corin在高血压等心血管疾病的发生中起重要作用。本文主要阐述Corin的分子结构、生物学功能、以及Corin在高血压性疾病中的作用,为高血压病的早期预测及治疗提供新的理论依据。     

阿托伐他汀对体外心肌细胞肥大的抑制作用

目的探讨阿托伐他汀体外抑制心肌肥厚的药理作用。方法体外培养新生大鼠的心室肌细胞,用血管紧张素Ⅱ(AngⅡ)诱导心肌细胞肥厚模型,以不同浓度的阿托伐他汀作用于心肌细胞,用软件分析测量心肌细胞表面积,3H-亮氨酸参入法检测心肌细胞蛋白合成速率及使用RT-PCR半定量测定心钠素(ANP),脑钠素(BNP)和特异分布于心脏的丝氨酸蛋白酶(Corin)的表达变化。结果AngⅡ可成功诱导体外培养的新生大鼠心室肌细胞肥大,表现为心肌细胞面积和3H-亮氨酸的参入增加,ANP、BNP、Corin表达升高等特征性改变,从而分析阿托伐他汀对心肌肥厚的作用。阿托伐他汀可逆转上述变化并呈剂量依赖性,而作为溶剂的DM-SO对肥大的心肌细胞差异无显著性。结论阿托伐他汀抑制AngⅡ介导的体外心肌细胞肥大,预示其具有降脂以外的其他重要药理作用。     

丝氨酸蛋白酶-Corin与心血管疾病

丝氨酸蛋白酶参与体内多种重要的病理生理过程,在食物消化、血压调节、凝血、纤溶及组织器官的发育等生理过程起重要的生物学功能.当人体血压增高或血容量增加时,A型利钠肽(ANP)和B型利钠肽(BNP)从心脏释放入血,产生利尿、排钠及血管舒张的作用.Corin是新发现的Ⅱ型跨膜丝氨酸蛋白酶,特异性分布于心脏,可将ANP前体和B...     

Identification of transplantable dopamine neuron precursors at different stages of midbrain neurogenesis

Protocols used for generation of mesencephalic dopamine (mesDA) neurons from stem cells, or fetal brain tissue, invariably result in cell preparations that are highly mixed in composition, containing mesDA neuron precursors in various states of fate commitment and differentiation. For further optimisation and refinement of these procedures it is essential to determine the optimal stage of development and phenotypic characteristics of cells used for grafting. We have used fluorescence-activated cell sorting procedures to isolate mesDA precursors in defined stages of differentiation from mouse ventral mesencephalon (VM), at embryonic day 10.5 (E10.5), when the mesDA neuron domain consists of proliferative radial glia-like cells expressing the mesDA neuron determinant Lmx1a and the floorplate marker Corin, and at E12.5, when the VM has expanded to comprise a mixture of proliferative progenitors, neuroblasts and young neurons. The sorted cells were transplanted to the striatum of 6-hydroxydopamine-lesioned rats. Results show that the Lmx1a/Corin-expressing ventricular zone progenitors, which are the source of mesDA neurons in grafts from E10.5 VM, had lost this capacity at E12.5. At this later stage all transplantable mesDA precursors resided in the intermediate zone as postmitotic Nurr1-expressing neuroblasts. The more differentiated, TH-expressing cells survived sorting and transplantation poorly. We also provide evidence that, during early mesDA neurogenesis, the progenitors for nigral mesDA neurons segregate to lateral parts of the Lmx1a-expressing domain and can be selectively isolated based on their level of Corin expression. These results have implications for current efforts to develop well-characterized stem cell-derived mesDA progenitor cell preparations for cell therapy.     

心脏心房利尿钠肽转换酶在妊娠期高血压疾病发病机制中的作用研究

目的探讨心房利尿钠肽转换酶(Corin)在妊娠期高血压疾病(hypertension disorders in pregnancy,HDP)发病中的作用,为HDP防治寻找潜在的防治靶点。方法收集乌鲁木齐市自治区人民医院北院2014年1月至2016年2月住院的HDP患者94例(HDP组),其中妊娠期高血压15例、轻度子痫前期34例、重度子痫前期32例、子痫13例。选取同期产检的正常产妇40例作为正常对照组。Corin酶的测定使用ELISA法。66例子痫前期患者根据随机数字法分为常规治疗对照组和丹红治疗研究组,每组33例。比较治疗后两组Corin表达、分娩时孕周、新生儿体重、围产儿死亡率、孕产妇死亡率和剖宫产率。结果正常对照组Corin酶表达水平为(186.4±31.7)pg/m L,显著高于HDP组的(142.4±19.5)pg/m L(P0.05)。妊娠期高血压组、轻度子痫前期组、重度子痫前期组和子痫组中Corin表达水平分别为(167.2±25.3)pg/m L、(151.4±20.1)pg/m L、(132.3±18.2)pg/m L和(115.7±14.6)pg/m L,4组间差异有统计学意义(P0.05)。常规治疗对照组和丹红治疗研究组在丹红治疗前Corin酶和24 h尿蛋白各项指标差异无统计学意义(P0.05),经丹红治疗后丹红治疗研究组Corin酶的升高和24 h尿蛋白减低显著优于常规治疗对照组(P0.05)。丹红治疗研究组的分娩时孕周、新生儿体重[(33.8±2.6)周、(1 792.5±224.2)g]显著优于常规治疗对照组[(32.4±2.4)周、(1 650.4±217.3)g](P0.05)。丹红治疗研究组围产儿死亡率为0%,孕产妇死亡率为0%,剖宫产率为90.9%,与常规治疗对照组的3.0%、0%和93.9%比较差异无统计学意义(P0.05)。结论 HDP孕妇体内存在Corin酶的异常低表达,丹红注射液可以显著升高Corin酶的表达,延长HDP孕周,增加新生儿体重,降低孕妇尿蛋白。