全身振动训练联合正弦交变电磁场对去卵巢骨质疏松大鼠骨密度、骨代谢指标的影响研究

目的探讨全身振动训练联合正弦交变电磁场对去卵巢骨质疏松大鼠骨密度、骨代谢、骨生物力学性能的影响。方法将100只大鼠随机分为切除卵巢组和对照组,分别进行卵巢切除术和假手术,大鼠进行6周恢复,恢复后将造模成功的切除卵巢大鼠随机分为模型组(MO组)、全身振动训练组(W组)、正弦交变电磁场组(S组)、全身振动训练+正弦交变电磁场组(WS组),对照组列为假手术组(SO组),进行为期16周干预,干预结束后对大鼠进行骨密度、骨代谢、骨生物力学性质的检测。结果16周干预完成后,MO组、S组大鼠体质量显著高于SO组、W组、WS组大鼠(P0. 05); W组、WS组、SO组大鼠骨密度指标、血清雌二醇浓度指标明显高于大鼠MO组(P0. 05); SO组大鼠血清雌二醇浓度指标明显高于S组、W组、WS组(P0. 05); M组大鼠血清OC、ALP浓度明显高于SO组、W组、S组、WS组大鼠(P0. 05);尿液DPD/Cre、Ca/Cre、P/Cre浓度方面,M组大鼠明显高于SO组、W组、S组、WS组大鼠(P0. 05)。SO组、W组、S组、WS组大鼠股骨最大载荷和弹性模型明显高于MO组大鼠(P0. 05)。SO组、W组、S组、WS组大鼠股骨断裂载荷组间无明显差异(P0. 05); SO组、W组、S组、WS组大鼠股骨弹性模量明显高于MO组大鼠(P0. 05)。SO组大鼠股骨弹性模量明显高于S组大鼠(P0. 05),但与W组、WS组大鼠没有明显差异(P0. 05)。L4椎体压缩试验,SO组、W组、S组、WS组大鼠股骨最大载荷和弹性模型明显高于MO组大鼠(P0. 05)。SO组大鼠高于S组、W组,差异有统计学意义(P0. 05),但与WS组大鼠没有明显差异(P0. 05)。结论全身振动训练、正弦交变电磁场、全身振动训练联合正弦交变电磁场3种干预方式施用于去卵巢骨质疏松大鼠均能提升骨密度、抑制骨吸收、平衡骨代谢、改善骨骼结构力学和材料力学性能。而全身振动训练联合正弦交变电磁场能的治疗效果优于单纯使用全身振动训练或正弦交变电磁场,在临床应用中有一定推广价值。     

Predicting healthcare expenditure by multimorbidity groups

Objectives

This article has two main purposes. Firstly, to model the integrated healthcare expenditure for the entire population of a health district in Spain, according to multimorbidity, using Clinical Risk Groups (CRG). Secondly, to show how the predictive model is applied to the allocation of health budgets.

腰椎间盘突出症动物模型的研究进展

近年来,腰椎间盘突出症发病率逐渐增高,由于动物模型对于阐明疾病发病机制及评估新的治疗方法具有重要作用,越来越多的学者开始研究如何建立合适的、能够更好地模拟人类腰椎间盘突出的动物模型。近期的研究多选用包括大鼠、兔、羊、猪等动物作为实验对象,通过物理或化学方式直接损伤其椎间盘或神经根,或通过限制实验动物的行为动作、改变其饲养环境以及性别年龄导致的生理因素等方式诱导其出现椎间盘退变。各种造模方法均有其特点及局限性,适用于不同情况,有必要继续完善。     

Utility of food pellets containing 1-aminobenzotriazole for longer term in vivo inhibition of cytochrome P450 in mice

1. The utility of 1-aminobenzotriazole (ABT), incorporated in food, has been investigated as an approach for longer term inhibition of cytochrome P450 (P450) enzymes in mice.

2. In rats, ABT inhibits gastric emptying, to investigate this potential limitation in mice we examined the effect of ABT administration on the oral absorption of NVS-CRF38. Two hour prior oral treatment with 100?mg/kg ABT inhibited the oral absorption of NVS-CRF38, T_max was 4?hours for ABT-treated mice compared to 0.5?hours in the control group.

3. A marked inhibition of hepatic P450 activity was observed in mice fed with ABT containing food pellets for 1?month. P450 activity, as measured by the oral clearance of antipyrine, was inhibited on day 3 (88% of control), week 2 (83% of control) and week 4 (80% of control).

4. T_max values for antipyrine were comparable between ABT-treated mice and the control group, alleviating concerns about impaired gastric function.

5. Inclusion of ABT in food provides a minimally invasive and convenient approach to achieve longer term inhibition of P450 activity in mice. This model has the potential to enable pharmacological proof-of-concept studies for research compounds which are extensively metabolised by P450 enzymes.     

三种智慧放疗计划预测模型的性能评价

目的比较三种智慧放疗计划预测模型的精度与泛化鲁棒性,为模型选择提供依据。方法收集45例前列腺癌和25例鼻咽癌临床放疗计划,运用Z、L、S模型预测前列腺癌中膀胱和直肠、鼻咽癌中左右腮腺的剂量体积直方图(DVH)。应用预测DVH与临床DVH曲线下面积的差别(|DVH预测-DVH临床|)评价预测误差,误差越小则预测精度越高。在单个危及器官(OAR)上比较3种预测模型的精度,并在不同OAR中计算各模型预测精度的标准差以评价和比较模型的泛化鲁棒性。结果对于膀胱和直肠,L模型的预测误差(0.114和0.163)显著大于Z和S模型(≤0.071,P<0.05);对于左腮腺,S模型的预测误差(0.033)与Z和L模型相近(≤0.025,P>0.05);对于右腮腺,S模型的预测误差(0.033)显著大于Z和L模型(≤0.028,P<0.05)。在不同OAR上,S模型的预测精度标准差比Z、L模型小(分别为0.016、0.018和0.060)。结论在前列腺癌膀胱和直肠的DVH预测中Z和S模型的精度较高,而在鼻咽癌左右腮腺中Z和L模型较高,在不同OAR上S模型的泛化鲁棒性相对较好。     

基于BGP、TGF-β1的表达探究蛇床子素对去卵巢致骨质疏松大鼠的作用

目的观察蛇床子素对去卵巢致骨质疏松大鼠的影响。方法选取3月龄雌性SD大鼠30只,随机分为蛇床子素组(A组)、模型对照组(B组)、假手术组(C组),各10只。A、B 2组摘除卵巢构建去势大鼠骨质疏松模型,C组仅进行手术、不摘除卵巢。造模成功后,分别给予相应药物灌胃,连续给药12周,处死。然后测量骨密度,检测治疗后血清BGP、TGF-β1、钙指标。结果B组大鼠股骨骨密度较C组明显降低(P<0.05);经12周治疗,A组股骨骨密度较B组明显升高(P<0.05)。与C组比较,B组大鼠血清中BGP含量升高、TGF-β1降低(P<0.05);与B组比较,A组大鼠血清中BGP降低、TGF-β1含量升高(P<0.05)。与C组比较,B组大鼠血清Ca水平明显降低(P<0.05);与B组比较,A组大鼠血清Ca水平明显升高(P<0.05)。差异均有统计学意义。结论蛇床子素能够有效通过调节大鼠体内激素分泌改善去卵巢大鼠的骨代谢异常,提高骨密度,对骨质疏松症起到一定的防治作用。     

Towards human ex vivo organ perfusion models to elucidate drug pharmacokinetics in health and disease

Abstract

To predict the absorption, distribution, metabolism and excretion (ADME) profile of candidate drugs a variety of preclinical models can be applied. The ADME and toxicological behavior of newly developed drugs are often investigated prior to assessment in humans, which is associated with long time-lines and high costs. Therefore, good predictions of ADME profiles earlier in the drug development process are very valuable. Good prediction of intestinal absorption and renal and biliary excretion remain especially difficult, as there is an interplay of active transport and metabolism involved. To study these processes, including enterohepatic circulation, ex vivo tissue models are highly relevant and can be regarded as the bridge between in vitro and in vivo models. In this review the current in vitro, in vivo and in more detail ex vivo models for studying pharmacokinetics in health and disease are discussed. Additionally, we propose novel models, i.e., perfused whole-organs, which we envision will generate valuable pharmacokinetic information in the future due to improved translation to the in vivo situation. These machine-perfused organ models will be particularly interesting in combination with biomarkers for assessing the functionality of transporter and CYP450 proteins.