Multi-compartmental modelling and experimental design for glucose transport studies in insulin-resistant rats

Many pathologies are associated with abnormalities of glucose metabolism or with perturbations of its transport (type 2 diabetes or insulin-resistance). The pre-diabetic state is characterised by a state of insulin-resistance, in others words a defect of glucose transport in insulin-sensible tissues, such as muscles and adipose tissues. The mathematical modelling of experimental data can be an excellent method to explore the mechanisms implied in the studied biological phenomenon. Thus, starting from a symbolic formulation like the compartmental modelling, it can be possible to develop a theoretical basis for the observation and to consider the best-adapted experiments for the study. We showed with mathematical models that [123I]-6-deoxy-6-iodo-D-glucose (6-DIG), shown as a tracer of glucose transport in vitro, could point out this transport abnormality. To quantify the insulin resistance, we estimated the fractional transfer coefficients of 6-DIG from the blood to the organs. We realised many studies to lead to a satisfying model; special attention has been paid to the precision of the parameter to select the best model. The results showed that by associating experimental data obtained with 6-DIG activities and an adapted mathematical model, discriminating parameters (in and out fractional transfer coefficients) between the two groups (control and insulin-resistant rats) could be pointed out.     

Genetic mapping of ossification of the posterior longitudinal ligament of the spine.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is recognized as a common disorder among Japanese and throughout Asia. Estimates of its prevalence are in the range of 1. 9%-4.3%. Although its etiology is thought to involve a multiplicity of factors, epidemiological and family studies strongly implicate genetic susceptibility in the pathogenesis of OPLL. In this study we report an identification of a predisposing locus for OPLL, on chromosome 6p, close to the HLA complex. The evidence for this localization is provided by a genetic-linkage study of 91 affected sib pairs from 53 Japanese families. In this sib-pair study, D6S276, a marker lying close to the HLA complex, gives evidence for strongly significant linkage (P = .000006) to the OPLL locus. A candidate gene in the region, that for collagen 11A2, was analyzed for the presence of molecular variants in affected probands. Of 19 distinct variants identified, 4 showed strong statistical associations with OPLL (highest P = .0004). These observations of linkage and association, taken together, show that a genetic locus for OPLL lies close to the HLA region, on chromosome 6p.     

Protein fold recognition without Boltzmann statistics or explicit physical basis.

We present a fast method for finding optimal parameters for a low-resolution (threading) force field intended to distinguish correct from incorrect folds for a given protein sequence. In contrast to other methods, the parameterization uses information from >10(7) misfolded structures as well as a set of native sequence-structure pairs. In addition to testing the resulting force field's performance on the protein sequence threading problem, results are shown that characterize the number of parameters necessary for effective structure recognition.     

参数仪器变量估计近似分布方差的一种算法

本文对更一般的结构模型给出了参数的一种常用的仪器变量估计近似分布方差的一种算法．并且给出了未知真值x服从指数分布的例子．此算法对生物科学中统计规律的探讨有一定的应用价值．     

火炬松胚性细胞悬浮培养物的生长参数变化

以火炬松（PinustaedaL.）成熟合子胚来源的胚性愈伤组织为材料建立了胚性细胞悬浮系,测定了其培养物的鲜重、干重、细胞体积和胚数及培养液中的pH值、电导率和蔗糖浓度等生长参数在培养过程中的变化动态。结果表明,在培养周期内,培养液中的pH值、电导率和蔗糖浓度的逐步降低与培养物的鲜重、干重、细胞体积和胚胎数的逐步增加保持一致性。在培养至18—21d,pH值、电导率和蔗糖浓度均接近或降到最低点,而胚数及细胞体积的增长都达到最高点。     

Resampling in Multiple‐Dose Factorial Designs

Multiple‐dose factorial designs may provide confirmatory evidence that (fixed) combination drugs are superior to either component drug alone. Moreover, a useful and safe range of dose combinations may be identified. In our study, we focus on (A) adjustments of the overall significance level made necessary by multiple testing, (B) improvement of conventional statistical methods with respect to power, distributional assumptions and dimensionality, and (C) construction of corresponding simultaneous confidence intervals. We propose novel resampling algorithms, which in a simple way take the correlation of multiple test statistics into account, thus improving power. Moreover, these algorithms can easily be extended to combinations of more than two component drugs and binary outcome data. Published data summaries from a blood pressure reduction trial are analysed and presented as a worked example. An implementation of the proposed methods is available online as an R package.     

选择性冠状静脉动脉化搭桥术中不同移植物的应用疗效比较

目的:对比选择性冠状静脉动脉化(SCVBG)搭桥治疗弥漫性右冠状动脉狭窄病变中选择乳内动脉和大隐静脉作为桥血管的治疗效果。方法:选择2008年10月到2014年10月在我院行SCVBG搭桥的84例患者资料,其中选择大隐静脉作为桥血管进行冠状静脉动脉化搭桥患者46例(大隐静脉桥组),选择乳内动脉作为桥血管进行冠状静脉动脉化搭桥患者38例(乳内动脉桥组)。随访记录两组患者的生存情况、近期复查超声心动图、冠状动脉CTA及心绞痛复发率。结果:乳内动脉桥组患者总生存率(100%)明显高于大隐静脉桥组(82.6%)(P0.05)。乳内动脉桥组患者桥血管和心中静脉通畅率(100%)明显大于大隐静脉桥组(54.35%)(P0.05)。两组患者左心室射血分数(LVEF)较治疗前明显增加,左心室舒张期末内径(LVEDD)较治疗前明显减小(P0.05)。治疗后,乳内动脉桥组患者心绞痛复发率明显小于大隐静脉桥组(P0.05)。结论:SCVBG搭桥治疗弥漫性右冠状动脉狭窄病变中,选择乳内动脉桥效果优于大隐静脉桥,能明显提高桥血管和心中静脉通畅率,降低心绞痛复发率。     

检测pT_(1-4a)N_(1-3)M_0期胃癌淋巴结微转移检测的临床意义

目的:探讨胃癌淋巴结微转移及临床病理因素对p T1-4aN1-3M0期胃癌患者术后5年无瘤生存率的影响。方法:选取我院2009年1月至12月期间胃肠外科单一手术组行D2胃癌根治术p T1-4aN1-3M0期患者63例1427枚HE染色阴性淋巴结,应用免疫组化法检测这些淋巴结中CK19表达,观察微转移的情况并分析发生微转移的胃癌患者临床病理特征及对患者5年无瘤生存率的影响。结果:临床病理分期p T1-4aN1-3M0胃癌患者中,经免疫组化染色,1427枚HE常规染色阴性淋巴结中CK19阳性表达率为15.49%(221/1427);63例胃癌患者中CK19表达阳性率39.68%(25/63);术后随访时间5.6~68.5月(平均时间43.88月),淋巴结中CK19阴性表达、阳性表达患者的总5年生存率分别为52.63%、28.00%;两者无瘤生存率差异有统计学意义(x2=8.677,P=0.003)。淋巴结CK19阳性表达与胃癌患者的肿瘤直径(P0.05)、浸润胃壁深度(P0.05)有关。COX生存回归分析显示淋巴结微转移为独立预后因素。25例患者发现淋巴结微转移并推荐再分期,再分期率39.68%(25/63)。结论:p T1-4aN1-3M0期胃癌病人,CK-19免疫组化法染色能检出常规HE染色阴性淋巴结中的微转移,有助于细化分期、判断预后及指导治疗。     

序贯旁路移植同期行内膜剥脱治疗严重弥漫性冠状动脉病变的临床研究

目的:探讨严重弥漫性冠状动脉病变患者在非体外循环下行序贯旁路移植手术联合内膜剥脱的临床效果及安全性。方法:按照随机数字表法将2011年3月~2013年3月我院收治的110例严重弥漫性冠状动脉病变患者分为治疗组54例和对照组56例。治疗组在非体外循环下行序贯旁路移植结合内膜剥脱治疗,对照组在非体外循环下行冠状动脉旁路移植结合内膜剥脱治疗,比较两组的临床效果及围手术期并发症。结果:治疗组围手术期死亡2例(3.70%),对照组死亡4例(7.14%),两组死亡率比较差异无统计学意义(x2=0.631,P=0.427)。围手术期内治疗组心肌梗死、严重心脑血管不良事件以及新发房颤的发生率低于对照组,差异有统计学意义(P0.05)。治疗组术后1年吻合口通畅程度和桥血管通畅程度均优于对照组,差异均有统计学意义(Z=-2.416,-2.456;P=0.016,0.014)。结论:在非体外循环下序贯旁路移植同期行内膜剥脱治疗严重弥漫冠状动脉病变具有并发症少、安全性高且疗效好的特点,值得临床推广使用。