Combined spectroscopy methods and molecular simulations for the binding properties of trametinib to human serum albumin

Trametinib is a novel anticancer drug for treating metastatic cutaneous melanoma. The present study probed into the binding of trametinib to human serum albumin (HSA) through spectroscopy methods and molecular simulations. Trametinib could quench the fluorescence of HSA through static quenching which could be probed via fluorescence spectroscopy and time-resolved fluorescence. Thermodynamic parameters and docking results indicated that hydrogen bonds and van der Waals forces play crucial roles in this binding process, which exerts almost no effect on the HSA conformation under synchronous fluorescence, three-dimensional fluorescence, circular dichroism spectra, and molecular dynamics simulations. Site marker displacement experiments and molecular docking reveal that trametinib primarily binds to Sudlow site I of HSA. In addition, the trametinib–HSA interaction was hardly influenced by varying amino acid (glutamine, alanine, glycine, and valine) concentrations. This study can provide useful information for the pharmacokinetic properties of trametinib.

Probing the binding properties of trametinib to human serum albumin.     

EGCG对去势雌性大鼠骨量丢失的预防作用

目的:研究表没食子儿茶素没食子酸酯[(-)-epigallocatechin-3-gallate,EGCG]早期预防雌性去势大鼠骨量丢失的作用?方法:12周龄雌性Sprague-Dawley大鼠分为3组:A组,双侧卵巢切除去势术后第3天开始连续12周以10 mg/(kg?d) EGCG腹腔内注射;B组,仅接受双侧卵巢切除去势术,不接受EGCG干预;C组,假手术组,不接受EGCG干预?在实验终点时刻(24周龄)制作大鼠胫骨和股骨的离体标本用于micro-CT扫描,测量骨密度(BMD)和相关骨形态学参数:松质骨骨组织总量(total bone volume,TV)?骨量(bone volume,BV)?骨体积分数?平均骨小梁厚度?平均骨小梁数量和骨小梁分离度?皮质骨厚度和皮质骨骨体积分数;并对大鼠股骨远端骨组织进行HE染色?结果:根据micro-CT分析,A组大鼠的BMD和骨体积分数显著高于B组(P < 0.05)?A组松质骨分离度显著低于B组(P < 0.05)?其余骨形态学参数3组之间无统计学差异(P > 0.05)?骨组织学研究显示C组松质骨密度较A组和B组更加致密,A组松质骨密度则介于B组和C组之间?结论:EGCG在延缓雌性大鼠骨量丢失方面有积极作用,但是在年轻的雌性大鼠卵巢切除去势后以10 mg/(kg?d)的剂量预防性腹腔注射EGCG并不能完全恢复丢失的骨量?     

融水小型猪的实验动物化系列研究概述

融水小型猪的种源来自广西融水县,2012年被引到广东繁育并测定了基础数据,包括种质特性、繁殖性能、生长曲线、血液学指标、血生化指标、脏器系数、染色体分析。参照国家和地方有关实验动物标准,初步建立了融水小型猪微生物与寄生虫、环境与设施、饲料、病理学、遗传学等质量控制标准。融水小型猪能适应当地气候,繁殖良好,自然受孕率为88.3%,妊娠期平均112 d,初产平均胎产仔6.1头,经产平均产仔7.9头。融水小型猪体型小,雌雄成年体重(6月龄)分别为17.21±5.20 kg和16.35±5.23 kg,性情温顺,线粒体DNA分析表明融水小型猪比兰屿猪更为古老。通过标准化的饲养管理与质量控制,具有培育成实验用小型猪的基本条件。     

Validating the Psychometric Characteristics of the Perinatal Posttraumatic Stress Disorder Questionnaire (PPQ) in a Chinese Context

Background

Perinatal posttraumatic stress disorder (PPTSD) is a common stress-induced mental disorder worldwide. The Perinatal Posttraumatic Stress Disorder Questionnaire (PPQ) is an excellent questionnaire that measures the symptoms of PPTSD, but has not been translated into Chinese yet.

DFT prediction of a novel molybdenum tetraboride superhard material

Although transition metal borides (TMBs) are promising superhard materials, the research and development of new TMB superhard materials is still a great challenge. Naturally, the Vickers hardness of TMBs is related to the 3D-network chemical bonding, in addition to the valence electron density and covalent bonds. In this paper, we apply ab initio calculations to explore the structural stability, Vickers hardness and hardening mechanism of MoB₄ tetraboride. Four possible tetraborides are predicted based on the phonon dispersion model. We find that MoB₄ with monoclinic structure (C2/m) and orthorhombic structure (Immm) are dynamically stable at the ground state. The calculated Vickers hardness of MoB₄ with monoclinic and orthorhombic structures is 41.3 GPa and 40.0 GPa, respectively. We suggest that the high hardness is derived from the 3D-network B–B covalent bond owing to bond synergistic effects. On the other hand, the Vickers hardness of MoB₄ decreases gradually with increasing pressure. The calculated results show that the hardness of MoB₄ is attributed to the B/G ratio and c/a ratio. Finally, we predict that MoB₄ is a new superhard material.

In this work, we predict that MoB₄ with monoclinic structure (C2/m) and orthorhombic structure (Immm) are potential superhard materials because of the 3D-network B–B covalent bonds. In addition, the hardness of MoB₄ is attributed to the B/G ratio and c/a ratio.     

Insulin sensitivity predicts glycemia after a protein load

Protein ingestion results in small but distinct changes in plasma glucose and insulin. We hypothesized that the glycemic and/or insulin response to protein might be related to the degree of insulin sensitivity. Our aim was to determine the relationships between insulin sensitivity (assessed by euglycemic-hyperinsulinemic clamp) and postprandial glucose, insulin, C-peptide, and glucagon responses to a 75-g protein meal and a 75-g glucose load. Sixteen lean healthy Caucasian subjects (mean +/- SD age, 25 +/- 6 years; body mass index [BMI], 23.1 +/- 1.7 kg/m2) participated in the study. After the protein meal, the mean plasma glucose declined gradually below fasting levels to a nadir of -0.36 +/- 0.46 mmol/L from 60 to 120 minutes, showing wide intraindividual variation. Insulin sensitivity (M value) was 1.1 to 3.9 mmol/L/m2 min in the subjects and correlated inversely with the plasma glucose response to the protein meal (r = -.58, P = .03), ie, the most insulin-sensitive subjects showed the greatest decline in plasma glucose. In contrast, there was no correlation between insulin sensitivity and the insulin or glucagon response to the protein load, or between the M value and the metabolic responses (glucose, insulin, C-peptide, and glucagon) to the glucose load. Our study suggests that the net effect of insulin and glucagon secretion on postprandial glucose levels after a protein meal might depend on the individual's degree of insulin sensitivity. Gluconeogenesis in the liver may be less susceptible to inhibition by insulin in the more highly resistant subjects, thereby counteracting a decline in plasma glucose.     

肝动脉化疗栓塞联合卡瑞利珠单抗治疗中晚期肝细胞癌的疗效分析

【摘要】 目的 评估肝动脉化疗栓塞（TACE）联合卡瑞利珠单抗治疗中晚期肝细胞癌（HCC）患者的疗效。方法 回顾性分析2019年6月至2021年9月106例中晚期HCC患者的临床资料。患者中接受TACE联合卡瑞利珠单抗治疗71例（联合组）,接受单药卡瑞利珠单抗治疗35例（对照组）。按1∶1比例应用倾向性得分匹配（PSM）分析2组患者疗效。主要研究终点为总生存期（OS）,次要研究终点为无进展生存期（PFS）。结果 成功匹配32对患者。PSM前,TACE联合卡瑞利珠单抗组的OS和PFS均高于单独卡瑞利珠单抗组（20.2个月比10.7个月,P=0.001;8.2个月比5.2个月,P=0.002）。PSM后,联合治疗组OS和PFS仍优于对照组（19.6个月比10.7个月,P=0.043;7.7个月比5.2个月,P=0.013）。PSM前多因素分析显示,单药卡瑞利珠单抗（P=0.006）和Child B级（P=0.027）是患者预后较差的影响因素,而PSM后的多因素分析并未发现影响患者OS的独立预后因素。此外,2组患者的治疗相关不良反应的发生率相似,差异无统计学意义（均P＞0.05）。结论 TACE联合卡瑞利珠单抗治疗中晚期肝癌比单药卡瑞利珠单抗具有更好的生存获益,并且安全可控。     

骨代谢指标测定在骨质疏松诊治中的应用价值

目的 比较妇女绝经前后骨代谢指标的变化，研究各指标在骨质疏松症治疗后的变化率，对各指标在骨质疏松症诊治中的应用作出初步评价。方法 48例绝经前妇女、48例绝经后妇女测定10项骨代谢指标．45例绝经后骨质疏松症患者．治疗前、治疗6个月后分别测定10项骨代谢指标，观察其变化率。12名绝经后妇女，每两个月测定10项骨代谢指标。共观察一年。结果 绝经后妇女骨代谢指标明显升高，绝经后骨质疏松症患者经抗吸收治疗后．大部分骨代谢指标明显降低，血清骨形成指标比尿骨吸收指标长期个体内的变异要小。结论 绝经后骨质疏松症患者骨转换加快，部分血清骨代谢指标优于尿骨代谢指标，尤以血清骨形成指标N—mid骨钙素和血清骨吸收指标CTX为优。     

HLA—DR2,DRB1＊0301,DQA1＊0501基因频率与肌炎及其临床表现的 …

目的：观察人类白细胞相关抗原ＨＬＡ－ＤＲ２，ＤＲＢ１＊０３０１，ＤＱＡ１＊０５０１基因频率为多发性肌炎／皮肌炎（ＰＭ／ＤＭ）发病及其临床表现的关系，方法：特异性引物聚合酶链式反应（ＰＣＲ－ＳＳＰ）方法分别测定了３１例ＰＭ／ＤＭ患者及５０例正常人的ＨＬＡ－ＤＲ２，ＤＲＢ１＊０３０１及ＨＬＡ－ＤＡＱ１＊０５０１的基因频率，结果：三种基因型在３１例肌炎患得中基频率分别为：６．４５％，９．６８％和７７．４     

Hepatic arterial infusion chemotherapy and embolization in the treatment of primary hepatic carcinoma

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