A novel case of endometrial dedifferentiated adenocarcinoma associated with MLH1 promotor hypermethylation and microsatellite instability

Endometrial dedifferentiated carcinoma is a rare, malignant tumor whose molecular alterations have not been clarified yet. We report a novel case of a 61-year old woman who presented with irregular vaginal bleeding after menopause and a 3?cm uterus mass. Histology revealed endometrial dedifferentiated adenocarcinoma, a rare subtype comprised of undifferentiated adenocarcinoma. The patient still survived 1?year after surgery without chemotherapy and radiotherapy. Immunohistochemistry revealed loss of MLH1/PMS2 expression and retained MSH2/MSH6 expression. Consistently, microsatellite instability was detected indicative of high microsatellite instability (MSI-H). No BRAF V600E, KRAS and POLE mutations were identified. Remarkably, the promoter regions of mutL homolog 1(MLH1) were methylated. Furthermore, several tumor cells were PD-L1 positive in this case with a concentration at the infiltrating tumor edge indicating MSI-H in endometrial dedifferentiated adenocarcinoma is a potential predictive factor for response to immunotherapy targeting the PD-1 or its ligand PD-L1.     

Twins with hereditary sensory and autonomic neuropathy type IV with preserved periodontal sensation

Turkish twin brothers affected with hereditary sensory and autonomic neuropathy type IV (HSAN IV) are reported. Their clinical findings were generally typical for HSAN IV. Interestingly they both had preserved periodontal sensation. Mutation analysis of the NTRK1 gene showed a homozygous c.2001C>T substitution in exon 15 in both twins. This base substitution is predicted to change a polar, positively charged amino acid arginine to the highly active amino acid cystein at position 654 (p.Arg654Cys). The parents were heterozygous for the mutation. This mutation has been reported previously in one Japanese and one Arab patients. The preserved periodontal sensation has not previously been reported in patients affected with HSAN IV. This preserved sensation in our patients might have been through Ruffini endings, the periodontal mechanoreceptors which have been reported to be present in TrkA knockout mice. Here we report the first twins affected with HSAN IV and the observation that periodontal sensation is not affected by mutation in NTRK1.     

性学人物研究王效道

王效道，1928年生，1952年毕业于北京辅仁大学教育系，曾任北京大学医学部医学心理学教研室负责人、中国高等医学教育学会医学心理学教育分会副会长、中国性学会秘书长、《中国性学》杂志主编等。在60年的职业生涯中，王效道为我国的心理卫生事业和性健康教育事业的建设和发展，以及中国性学会和《中国性学》杂志的创办和发展，都做出了重大的贡献。     

Pharmacokinetics of Peptide–Fc Fusion Proteins

Peptide–Fc fusion proteins (or peptibodies) are chimeric proteins generated by fusing a biologically active peptide with the Fc-domain of immunoglobulin G. In this review, we describe recent studies that have evaluated the absorption, distribution, metabolism, and excretion characteristics of peptibodies. Key features of the pharmacokinetics of peptibodies include their extended half-life due to recycling by the neonatal Fc receptor (FcRn), a substantial contribution by renal excretion to total clearance and, for certain peptibodies, target-mediated drug disposition. The prolonged half-life of peptibodies permits less-frequent dose administration compared with small therapeutic peptides, thereby supporting patient convenience and compliance. Hence, a considerable number of peptibodies are currently in preclinical and clinical development. Investigation of the metabolism (biotransformation) of biologics is an evolving area of research: ligand-binding mass spectrometry techniques have been employed for the characterization of the peptibody romiplostim, providing a new approach to evaluation of the degradation products of biologics. Pharmacokinetic/pharmacodynamic modeling and simulation techniques have been used to predict the pharmacokinetics of peptibodies which can inform clinical decision-making, particularly selection of dosing regimens. This integrated review highlights the distinct pharmacokinetic characteristics of peptibodies and their influence on the drug development process for this emerging family of therapeutics. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:53–64, 2014     

圆锥角膜基质环植入术的研究进展

角膜基质环植入术(ICRS)是一种用于治疗轻中度圆锥角膜的手术方法。ICRS是通过植入基质环,使中央角膜扁平化,弧长缩短,角膜曲率半径增大,屈光力降低,从而改善角膜前突导致的轴性近视眼与不规则散光。ICRS具有微创性、安全性、有效性、可逆性且并发症少等优点,其中长期疗效较佳。本文中笔者就ICRS的发展史、适应症、手术方法、手术疗效的影响因素、术后处理及疗效的评估等方面进行阐述。     

Sustained Release of Metformin via Red Blood Cell Accumulated Sulfenamide Prodrug

Metformin is a first-line antidiabetic drug to treat type 2 diabetes. It is rapidly eliminated from plasma but also accumulated into red blood cells (RBCs) from which it is slowly released back into plasma. The aim of the study was to evaluate whether the amount of metformin in the RBCs could be increased by a sulfenamide prodrug approach, which could provide longer duration of metformin in systemic circulation. Pharmacokinetic properties of metformin and its cyclohexyl sulfenamide prodrug were evaluated in plasma and in whole blood after intravenous and oral administration in rats. Once the sulfenamide prodrug reached the bloodstream, it was rapidly and efficiently accumulated into the RBCs, where it was converted to metformin by free thiols. The RBC–whole blood ratio of metformin was increased approximately from 42% to 96% when metformin was administered intravenously as its sulfenamide prodrug, and the proportion of metformin in the RBCs was found to be concentration and time independent. Because metformin was slowly liberated into plasma, the prodrug showed a sustained-release pharmacokinetic profile and longer plasma half-life for metformin after oral administration. Therefore, this sulfenamide prodrug has great potential to improve metformin therapy as the daily doses could be reduced.     

无肌松喉罩静脉麻醉在支气管镜检查中的应用

目的评价不应用肌松药的喉罩静脉麻醉用于患者支气管镜检查的可行性和安全性。方法行支气管镜检查患者60例,随机均分为无肌松喉罩静脉麻醉组(Ⅰ组)和使用肌松药麻醉组(Ⅱ组)。记录检查及喉罩操作过程中的生命体征,记录麻醉效果评级、检查中不良反应及患者满意度等。结果与镜检前比较,Ⅰ组各时点患者收缩压(SBP)、舒张压(DBP)、心率(HR)明显下降,脉搏血氧饱和度(Sp O2)明显升高(P0.05),Ⅱ组拔除喉罩时患者SBP、DBP与镜检前比较无差异(P0.05),HR明显增快、Sp O2明显升高(P0.05)。I组患者在拔除喉罩时SBP、DBP、HR较Ⅱ组低(P0.05)。两组不良反应发生率及患者满意度差异无统计学意义。结论无肌松喉罩静脉麻醉用于患者支气管镜检查安全可行,是一项值得推广的技术。     

Correlation between antiplatelet resistance and recurrent cardiac ischemic events of patients with acute myocardial infarction

<正>Objective To evaluate the predictive value of anti-platelet resistance assessed by whole blood electronic impedance aggregometry(EIA) for the risk of recurrent cardiac ischemic events in patients with acute myocardial infarction(AMI) who underwent coronary stenting. Methods We enrolled