Long-term follow-up of camouflage effects following resin infiltration of post orthodontic white-spot lesions in vivo

Objectives:To reassess the long-term camouflage effects of resin infiltration (Icon, DMG, Hamburg, Germany) of white spot lesions (WSL) and sound adjacent enamel (SAE) achieved in a previous trial. The null hypothesis was tested that there were no significantly different CIE-L*a*b*-ΔE-values between WSL and SAE areas of assessment after at least 24 months (T24) compared to those at baseline (T0).Materials and Methods:Of twenty subjects who received previous resin infiltration treatment of n_teeth = 111 nonrestored, noncavitated postorthodontic WSL after multibracket treatment during a randomized controlled trial and were contacted 20 months after baseline, eight subjects (trial teeth n_teeth = 40; m/f ratio 1/7; age range (mean; SD) 12–17 [15.25; 2.12] years); response rate: 40%) were available for follow-up after at least 24 months (T24). CIE-L*a*b* differences between summarized color and lightness values (ΔE_WSL/SAE) of WSL and SAE were assessed using a spectrophotometer and compared to baseline data assessed prior to infiltration (T0), and those after 6 (T6), and 12 (T12) months using paired t tests at a significance level of α = 5%.Results:T24 assessments were performed after a mean 33.86 (SD: 8.64; Min: 24; Max: 45) months following T0. Mean (SD) ΔE_WSL/SAE units of available teeth were 8.76 (5.33) at baseline; 5.5 (2.75) at T6; 5.2 (2.41) at T12; and 5.57 (2.6) at T24. Comparisons of T6, T12, and T24 with T0 yielded highly significant differences, whereas T6–T24 and T12–T24 differences were found to be not significant.Conclusions:Assimilation of infiltrated WSL to the color of adjacent enamel by resin infiltration is considered to be suitable for the long-term improvement in the esthetic appearance of postorthodontic WSL.     

CYP2C19*3基因多态性对癫痫患者奥卡西平活性代谢产物MHD浓度的影响

目的：分析CYP2C19*3基因多态性与癫痫患者奥卡西平（oxcarbazepine，OXC）活性代谢产物10，11-二氢-10-羟基卡马西平（monohydroxycarbazepine，MHD）血药浓度的相关性。方法：纳入120例OXC单药治疗1个月以上且症状控制良好的癫痫患者，采集清晨服药前空腹血，采用高效液相色谱法测定MHD稳态谷浓度。通过PCR和sanger测序判定患者CYP2C19*3基因型。结果：120例癫痫患者快代谢患者64例，MHD血浆浓度为（18.17±7.34）μg·mL^-1；中代谢型患者36例，MHD血浆浓度为（19.31±9.17）μg·mL^-1；慢代谢型患者20例，MHD血浆浓度为（25.79±7.51）μg·mL^-1，3种基因型的MHD浓度有显著性差异（F=7.077，P=0.0013）。多因素分析显示，日剂量作为影响血药浓度的重要指标呈现出显著相关性（P<0.05）。结论：CYP2C19*3基因多态性影响MHD血药浓度，并且日剂量越高，MHD血药浓度越大，两者成显著正相关，临床应进行血药浓度监测。     

Minor contribution of CYP3A5 to the metabolism of hepatitis C protease inhibitor paritaprevir in vitro

1. Paritaprevir (PTV) is a non-structural protein 3/4A protease inhibitor developed for the treatment of hepatitis C disease as a fixed dose combination of ombitasvir (OBV) and ritonavir (RTV) with or without dasabuvir.

2. The aim of this study was to evaluate the effects of cytochrome P450 (CYP) 3A5 on in vitro PTV metabolism using human recombinant CYP3A4, CYP3A5 (rCYP3A4, rCYP3A5) and human liver microsomes (HLMs) genotyped as either CYP3A5*1/*1, CYP3A5*1/*3 or CYP3A5*3/*3.

3. The intrinsic clearance (CL_int, V_max/K_m) for the production of a metabolite from PTV in rCYP3A4 was 1.5 times higher than that in rCYP3A5. The PTV metabolism in CYP3A5*1/*1 and CYP3A5*1/*3 HLMs expressing CYP3A5 was comparable to that in CYP3A5*3/*3 HLMs, which lack CYP3A5.

4. CYP3A4 expression level was significantly correlated with PTV disappearance rate and metabolite formation. In contrast, there was no such correlation found for CYP3A5 expression level.

5. This study represents that the major CYP isoform involved in PTV metabolism is CYP3A4, with CYP3A5 having a minor role in PTV metabolism. The findings of the present study may provide foundational information on PTV metabolism, and may further support dosing practices in HCV-infected patients prescribed PTV-based therapy.

     

汉族人拉莫三嗪相关过敏反应与HLA-B*1502的相关性

目的研究在汉族人中拉莫三嗪相关过敏反应是否与HLA-B*1502有相关性。方法对在郑州人民医院诊断为癫痫的患者在服用拉莫三嗪前进行HLA-B*1502测定,将服用拉莫三嗪12周后出现过敏反应者作为实验组,未出现过敏反应者作为对照组1,服用其他非芳香族抗癫痫药物出现过敏反应者为对照组2,检测对照组2的HLA-B*1502阳性率,对3组间HLA-B*1502的阳性率进行比较。结果实验组HLA-B*1502的阳性率为41.86%,对照组1为14.02%,对照组2为13.33%.实验组阳性率高于对照组1(χ2=13.86,P<0.05)及对照组2(χ2=6.83,P=0.009),对照组1与对照组2比较差异无统计学意义(χ2=0.009,P=0.924)。结论HLA-B*1502可能与汉族人拉莫三嗪相关过敏反应相关。     

医学期刊编辑胜任特征研究及其提升途径

【目的】 了解我国医学期刊编辑能力素质现状,并探讨其提升途径。【方法】 以胜任特征研究为基础,探讨我国医学期刊编辑的关键胜任特征,并从素质、技能、知识3个维度了解我国医学期刊编辑能力素质现状,分析我国医学期刊编辑所需及待提高的能力素质。【结果】 通过我国医学期刊编辑胜任特征重要程度及符合情况调查,成功建立我国医学期刊编辑胜任特征模型。我国医学期刊编辑总体能力素质情况良好,但需在判断能力、系统思考能力以及医学知识3个方面加以提升。【结论】 我国医学期刊编辑能力素质的提升是一个系统工程,它既要医学期刊编辑自身努力、主动学习、勇于实践,也离不开各级有关部门的组织、规划、重视与领导。医学期刊单位可将胜任特征模型应用于编辑招聘、人才发展、职业规划与绩效管理中,使理论模型转化成可为实际工作所用的工具。广大医学期刊编辑应努力成为高素质复合型人才,与时俱进,才能出色完成编辑工作,将医学期刊办好、办精。     

Hemorrhage promotes chronic adverse remodeling in acute myocardial infarction: a T1, T2 and BOLD study

Hemorrhage is recognized as a new independent predictor of adverse outcomes following acute myocardial infarction. However, the mechanisms of its effects are less understood. The aim of our study was to probe the downstream impact of hemorrhage towards chronic remodeling, including inflammation, vasodilator function and matrix alterations in an experimental model of hemorrhage. Myocardial hemorrhage was induced in the porcine heart by intracoronary injection of collagenase. Animals (N = 18) were subjected to coronary occlusion followed by reperfusion in three groups (six/group): 8 min ischemia with hemorrhage (+HEM), 45 min infarction with no hemorrhage (I ? HEM) and 45 min infarction with hemorrhage (I + HEM). MRI was performed up to 4 weeks after intervention. Cardiac function, edema (T₂, T₁), hemorrhage (T₂*), vasodilator function (T₂ BOLD), infarction and microvascular obstruction (MVO) and partition coefficient (pre‐ and post‐contrast T₁) were computed. Hemorrhage was induced only in the +HEM and I + HEM groups on Day 1 (low T₂* values). Infarct size was the greatest in the I + HEM group, while the +HEM group showed no observable infarct. MVO was seen only in the I + HEM group, with a 40% occurrence rate. Function was compromised and ventricular volume was enlarged only in the hemorrhage groups and not in the ischemia‐alone group. In the infarct zone, edema and matrix expansion were the greatest in the I + HEM group. In the remote myocardium, T₂ elevation and matrix expansion associated with a transient vasodilator dysfunction were observed in the hemorrhage groups but not in the ischemia‐alone group. Our study demonstrates that the introduction of myocardial hemorrhage at reperfusion results in greater myocardial damage, upregulated inflammation, chronic adverse remodeling and remote myocardial alterations beyond the effects of the initial ischemic insult. A systematic understanding of the consequences of hemorrhage will potentially aid in the identification of novel therapeutics for high‐risk patients progressing towards heart failure.     

Ultrashort echo time imaging with bicomponent analysis

Biological tissues frequently contain different water compartments, and these often have distinct transverse relaxation times. Quantification of these may be problematic on clinical scanners because spin echo sequences usually have initial echo times that are too long to accurately quantify shorter relaxation time components. In this study, an ultrashort echo time pulse sequence was used together with bicomponent analysis to quantify both the short and long T(2) components in tissues of the musculoskeletal system. Feasibility studies were performed using numerical simulation, and on phantoms and in vitro tissues including bovine cortical bone, ligaments, menisci, tendons, and articular cartilage. The simulation and phantom studies demonstrated that this technique can quantify T(2) * and fractions of the short and long T(2) components. The tissues studies showed two distinct components with short T(2) *s ranging from 0.3 ms for bovine cortical bone to 2.1 ms for menisci, and long T(2) *s ranging from 2.9 ms for bovine cortical bone to 35.0 ms for articular cartilage. The short T(2) * fraction ranged from 18.5% for patella cartilage to 80.9% for ligaments. The results show that ultrashort echo time imaging with bicomponent analysis can quantify the short and long T(2) water components in vitro in musculoskeletal tissues.