基于雨课堂的临床流行病学教学改革与实践

目的探讨雨课堂在临床流行病学教学中的作用和效果。方法采用随机对照法在本科阶段无流行病学学习经历的临床专业硕士研究生中,使用雨课堂线上课前预习及课后随堂练习的功能,用于评价雨课堂线上功能的辅助教学效果。结果应用雨课堂线上功能干预组与对照组在基线、阶段小测和末考卷面成绩均无统计学差异;但对于主动学习,雨课堂参与度较高的学生成绩提高明显。结论雨课堂有利于理论性较强课程的学习,但是仍不能忽略课堂教学师生互动过程。     

Estimation of phase signal change in neuronal current MRI for evoke response of tactile detection with realistic somatosensory laminar network model

Magnetic field generated by neuronal activity could alter magnetic resonance imaging (MRI) signals but detection of such signal is under debate. Previous researches proposed that magnitude signal change is below current detectable level, but phase signal change (PSC) may be measurable with current MRI systems. Optimal imaging parameters like echo time, voxel size and external field direction, could increase the probability of detection of this small signal change. We simulate a voxel of cortical column to determine effect of such parameters on PSC signal. We extended a laminar network model for somatosensory cortex to find neuronal current in each segment of pyramidal neurons (PN). 60,000 PNs of simulated network were positioned randomly in a voxel. Biot–savart law applied to calculate neuronal magnetic field and additional phase. The procedure repeated for eleven neuronal arrangements in the voxel. PSC signal variation with the echo time and voxel size was assessed. The simulated results show that PSC signal increases with echo time, especially 100/80 ms after stimulus for gradient echo/spin echo sequence. It can be up to 0.1 mrad for echo time = 175 ms and voxel size = 1.48 × 1.48 × 2.18 mm³. With echo time less than 25 ms after stimulus, it was just acquired effects of physiological noise on PSC signal. The absolute value of the signal increased with decrease of voxel size, but its components had complex variation. External field orthogonal to local surface of cortex maximizes the signal. Expected PSC signal for tactile detection in the somatosensory cortex increase with echo time and have no oscillation.     

Binding mode of conformations and structure-based pharmacophore development for farnesyltransferase inhibitors

Farnesyltransferase (FTase) is one of the prenyltransferase family enzymes that catalyse the transfer of 15-membered isoprenoid (farnesyl) moiety to the cysteine of CAAX motif-containing proteins including Rho and Ras family of G proteins. Inhibitors of FTase act as drugs for cancer, malaria, progeria and other diseases. In the present investigation, we have developed two structure-based pharmacophore models from protein–ligand complex (3E33 and 3E37) obtained from the protein data bank. Molecular dynamics (MD) simulations were performed on the complexes, and different conformers of the same complex were generated. These conformers were undergone protein–ligand interaction fingerprint (PLIF) analysis, and the fingerprint bits have been used for structure-based pharmacophore model development. The PLIF results showed that Lys164, Tyr166, TrpB106 and TyrB361 are the major interacting residues in both the complexes. The RMSD and RMSF analyses on the MD-simulated systems showed that the absence of FPP in the complex 3E37 has significant effect in the conformational changes of the ligands. During this conformational change, some interactions between the protein and the ligands are lost, but regained after some simulations (after 2 ns). The structure-based pharmacophore models showed that the hydrophobic and acceptor contours are predominantly present in the models. The pharmacophore models were validated using reference compounds, which significantly identified as HITs with smaller RMSD values. The developed structure-based pharmacophore models are significant, and the methodology used in this study is novel from the existing methods (the original X-ray crystallographic coordination of the ligands is used for the model building). In our study, along with the original coordination of the ligand, different conformers of the same complex (protein–ligand) are used. It concluded that the developed methodology is significant for the virtual screening of novel molecules on different targets.     

Dying is the Most Grown-Up Thing We Ever Do: But Do Health Care Professionals Prevent Us from Taking It Seriously?

This paper takes a somewhat slant perspective on flourishing and care in the context of suffering, death and dying, arguing that care in this context consists principally of ‘acts of work and courage that enable flourishing’. Starting with the perception that individuals, society and health care professionals have become dulled to death and the process of dying in Western advanced health systems, it suggests that for flourishing to occur, both of these aspects of life need to be faced more directly. The last days of life need to be ‘undulled’. Reflections upon the experiences of the author as carer and daughter in the face of her mother’s experience of death are used as basis for making suggestions about how care systems and professionals might better assist people in dealing with ‘the most grown up thing’ humans ever do, which is to die.     

蒜氨酸抗菌机制研究

目的 检测蒜氨酸最低抑菌浓度（MIC）与最低杀菌浓度（MBC），探讨蒜氨酸体内外抗菌机制。方法 体外微量稀释法检测蒜氨酸MIC和MBC，荧光显微镜观察菌体表面蒜氨酸，探讨蒜氨酸抗菌机制。体内蒜氨酸和青霉素分别治疗金葡菌感染家兔脓肿，检测脓汁标本中细菌存活情况，探讨体内蒜氨酸抗菌作用。结果 蒜氨酸对大肠杆菌、伤寒杆菌、金黄色葡萄球菌、白色葡萄球菌的MIC分别为3.047 μg·mL^-1、6.094 μg·mL^-1、0.386 μg·mL^-1、0.386 μg·mL^-1，蒜氨酸体外无杀菌活性。浓汁标本：死菌率蒜氨酸治疗组显著高于阴性对照组（P < 0.01），与青霉素治疗组无明显差异（P > 0.05）；活菌率蒜氨酸治疗组显著低于阴性对照组（P < 0.01），与青霉素治疗组无明显差异（P > 0.05）。结论 蒜氨酸与菌体蛋白、细菌酶蛋白结合阻断细菌与环境物质交换，抑制细菌生命活动，具有较强的抑菌作用，无杀菌活性；蒜氨酸体内代谢成大蒜素，具有较强杀菌作用。     

Nanomedicines: From Bench to Bedside and Beyond

Advancing nanomedicines from concept to clinic requires integration of new science with traditional pharmaceutical development. The medical and commercial success of nanomedicines is greatly facilitated when those charged with developing nanomedicines are cognizant of the unique opportunities and technical challenges that these products present. These individuals must also be knowledgeable about the processes of clinical and product development, including regulatory considerations, to maximize the odds for successful product registration. This article outlines these topics with a goal to accelerate the combination of academic innovation with collaborative industrial scientists who understand pharmaceutical development and regulatory approval requirements—only together can they realize the full potential of nanomedicines for patients.     

25-羟维生素D_3治疗2型糖尿病患者早期肾损害的临床观察

目的观察25-羟维生素D3(Vit D3)对2型糖尿病(T2DM)患者早期肾损害的临床疗效。方法纳入T2DM早期肾损伤患者80例,采用随机数字表法等分为治疗组与对照组,对照组继续原有降糖方案,治疗组在既往用药基础上,肌肉注射Vit D3注射液,疗程均为10个月,治疗结束后进行疗效评价。结果 1与治疗前相比,治疗组糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)水平上调,微量白蛋白(MA)、β2-微球蛋白(β2-M)及肾脏损伤分子-1(KIM-1)水平下调,治疗组低于对照组差异有统计学意义(P<0.05)。2与治疗前相比,治疗组治疗后Vit D3水平上调,治疗组高于对照组差异有统计学意义(P<0.01)。3T2DM患者Vit D3水平与MA(r=-0.432),β2-M(r=-0.615),及KIM-1(r=-0.763)水平均呈负相关(P<0.05)。结论 Vit D3可有效减轻T2DM患者的早期肾损害,对肾脏具有保护作用。