基于计算机辅助药物设计的清肺排毒汤多靶点系统治疗新型冠状病毒肺炎(COVID-19)物质基础探究

目的通过对清肺排毒汤功效和新型冠状病毒肺炎(COVID-19)病机的分析,基于计算机辅助药物设计(CADD)从多靶点结构出发系统探索清肺排毒汤排毒、抑制炎症风暴、利水渗湿3个方面的物质基础和分子机制。方法 TCMSP下载清肺排毒汤成分,基于血管紧张素转化酶II(ACE2)、白细胞介素-6受体(IL-6R)和水通道蛋白(AQP)分别进行分子对接虚拟筛选并对其结合模式进行分析。对利水药白术、茯苓、猪苓、泽泻进行反向靶点预测和GO分析和KEGG通路富集分析,预测其作用机制。结果阻断病毒作用最突出的前3位中药为甘草、麻黄、枳实,抑制炎症作用最突出的前3位中药是甘草、柴胡、紫菀;清肺排毒汤4个子方中,小柴胡汤阻断病毒、抑制炎症风暴的潜在活性化合物数均排第1。槲皮素及其衍生物对ACE2和IL-6R2个靶点均具有较强结合能力,是潜在的双靶点活性化合物。ACE2的Lys353残基是化合物与ACE2结合的关键位点。白术、茯苓、猪苓、泽泻缺乏阻断病毒、抑制炎症风暴的化合物,分子对接结果显示,这4味药材中含有的东莨菪内酯、去氢齿孔酸、α-D-半乳糖、环氧泽泻烯具有与水通道蛋白4(AQP4)的潜在结合能力。结论清肺排毒汤可通过多种化合物分别与ACE2、IL-6R、AQP4结合,发挥排毒、抑制炎症风暴、利水渗湿的作用;各组成子医方配伍合理,通过多点协同、优势互补发挥防治作用;得到了中药阻断新型冠状病毒(SARS-Co V-2)成分关键的结合位点Lys353,为清肺排毒汤药效机制的多角度挖掘和单体成分的现代化开发提供线索。     

星点设计-效应面法优化pH值响应及线粒体靶向双功能金丝桃苷脂质体的处方及其体外评价

目的 优化线粒体靶向金丝桃苷脂质体（DLD/Hyp-Lip）制备的最佳处方，并研究研究其在胎牛血清中的稳定性及体外释放行为，考察其线粒体靶向性。方法 采用薄膜分散法制备DLD/Hyp-Lip，以包封率和载药量为考察指标进行单因素实验，考察磷脂总量与金丝桃苷（hyperoside，Hyp）用量比、二硬脂酰磷脂酰乙醇胺-聚乙二醇（DSPE-PEG）与DLD用量比等条件对DLD/Hyp-Lip的影响，结合星点设计-效应面法优化DLD/Hyp-Lip处方。使用透射电子显微镜和粒径仪观察测定脂质体粒子外观、平均粒径和Zeta电位，采用血清稳定性实验和体外释药、线粒体靶向性对该载药系统进行评价。结果 DLD/Hyp-Lip最佳处方为磷脂总量和金丝桃苷用量比为12.50：1，磷脂总量与胆固醇用量比为6.00：1，DSPE-PEG与DLD用量比为3：5；测得金丝桃苷包封率为（95.57±0.56）%，载药量为（8.55±0.57）%。所制备的DLD/Hyp-Lip外观良好，平均粒径为（124.9±3.4）nm，Zeta电位为（-6.2±1.9）mV；在胎牛血清中性状稳定，在体外释放介质中24 h累积释放量达到40%。线粒体靶向实验表明DLD/Hyp-Lip可以促进药物聚集在线粒体部位。结论 采用此方法能够精准有效的优化DLD/Hyp-Lip的制备工艺，该方法操作简单方便，可以用于DLD/Hyp-Lip制备与处方的优化，制备的DLD/Hyp-Lip包封率高，粒径小，分布均匀，且具有良好的缓释作用，为DLD/Hyp-Lip的进一步体内研究奠定了基础。载金丝桃苷的DLD/Hyp-Lip具有良好的肝癌细胞线粒体靶向性，是一种潜在高效的肝癌细胞线粒体靶向给药系统。     

Powered off-road wheelchair for the transportation of tetraplegics along mountain trails

Purpose: For off-road mobility, some manual or power assisted devices were conceived to be self-driven by paraplegics while for tetraplegics non power-assisted devices were conceived. These devices require one or more conductors who are subjected to a high physical demand thus potentially creating: precarious safety condition for the user an elevated physical demand of conductors could reduce the care and the attention to give to the user; the time of the outdoor adventure experience of the user could be limited.

Methods: To address these issues, an innovative user-centered power assisted off-road wheelchair for the transportation of tetraplegics along mountain trails was developed. The device, structured like a trike, is driven by two healthy conductors; the user is placed in the middle of the frame. A movable seat provides for the transfer from the standard to the off-road wheelchair. An electrical motor, powered by a battery pack, provides for the actuation. All the design and prototype aspects, the control system and experimental tests are detailed.

Results: The prototype satisfies mechanical, safety and duration requirements. No physical demand while using the device and for the transfer of the user to the device was identified. Fun and engaging tests were carried out and all the participants were involved.

• Implications for Rehabilitation

• The device has the potential to enhance the quality of life of tetraplegics in terms of new life experiences.

• The device revealed the real possibility of a full recreational experience, an enhanced participation and a better social integration of tetraplegics.

     

仙灵骨葆制剂上市后临床安全性真实世界多维度研究设计

药品上市后临床安全性研究应开展真实世界的多维度设计,充分考虑多种来源的数据、证据及证据的整合。论文以仙灵骨葆制剂的上市后临床安全性研究设计为例,报告了国家不良反应监测中心自发呈报系统数据、医院信息系统数据、文献数据的统计分析以及数据、分析结果和证据的整合,通过证据整合发现:仙灵骨葆制剂的一般ADR主要是胃肠系统损害,表现为恶心、呕吐、口干、便秘、腹泻等;严重ADR主要表现为肝胆系统损害,表现为肝功能异常、肝酶升高、肝细胞损害等;过敏反应有时候表现为一般ADR,有时候表现为严重ADR;肝功能异常具有性别差异,女性比例偏高;肝功能异常出现3~7 d和15 d及以2个发病高峰,提示可能存在不同的发病机制;恶心、呕吐和胃功能紊乱是仙灵骨葆制剂的ADR预警信号。论文进一步讨论了回顾性数据对于前瞻性研究设计的支撑,初步明确了安全性真实世界多维度研究设计中主要数据源的优势和不足,从安全性证据的角度分析了数据之间的互补性和相应研究的时序性。     

Changes in Health Literacy during the first year following a kidney transplantation: Using the Health Literacy Questionnaire

ObjectivesThe study aimed to identify changes in health literacy (HL) and associated variables during the first year following a kidney transplantation.MethodsA total of 196 transplant recipients were included in a prospective follow-up study. The patients answered the Health Literacy Questionnaire (HLQ) at 5 days, 8 weeks, 6 and 12 months following the kidney transplantation. Mixed linear models were used to analyze changes in HL and backward elimination was used to identify variables associated with HL.ResultsTwo main patterns of change were identified: a) HL increased during the first 8 weeks of close follow-up and b) in several domains, the positive increase from 5 days to 8 weeks flattened out from 5 days to 6 and 12 months. Self-efficacy, transplant-related knowledge, and general health were core variables associated with HL.ConclusionsOverall, HL increased during the 8 weeks of close follow-up following the kidney transplantation, while 6 months seem to be a more vulnerable phase. Furthermore, low self-efficacy, less knowledge, and low self-perceived health may represent vulnerable characteristics in patients.Practical implicationsFuture kidney transplant care should take into account patients’ access to and appraisal of health information and social support, and draw attention to potentially vulnerable groups.     

甲状腺癌术后复发再手术中甲状旁腺和神经保护

甲状腺癌是一种十分常见的恶性肿瘤，其病理类型大多数为分化型甲状腺癌，经规范化治疗，预后较好，但仍有部分病人复发，且长期随访，可有高达30%以上的复发或转移率。因此，再次手术是甲状腺外科医师不可避免的问题，甚至在未来一段时间会成为一个临床常见情况。再次手术，尤其是Ⅵ区淋巴结复发的再次手术，往往有较高的手术难度和风险，需要谨慎地选择手术时机和入路，术中应用神经监测与传统显露技术相结合以保护喉返神经，运用传统识别和保护手法，选择性应用纳米炭、甲状旁腺素试纸、近红外自体荧光显像等技术以保护甲状旁腺功能。     

数字化口腔种植外科导板的精确度研究

目的本研究通过分析种植体术前设计和术后的三维位置,来评估数字化口腔种植导板的精确度。方法根据修复体的生物学功能和美学要求,使用3D种植软件对种植体位置进行设计。将设计的种植导板转化为手术用种植导板,指导47颗种植体植入合适位置。通过重叠术前和术后的CT扫描图像,分析植体肩部和根部的线性误差以及植体长轴的角度误差,比较植体设计和实际植入的3D位置。结果通过比较47颗种植体发现,种植体肩部的平均误差为(0.58±0.23)mm,种植体根部的平均误差为(0.66±0.30)mm,而角度平均误差为(2.40±1.02)°。结论与传统种植手术相比,数字化无翻瓣种植技术为临床医生提供方便;然而,为确保可预测的治疗结果,精确的术前设计是必须的,如此才不会导致可能出现的术中和术后并发症。     

BOPPPS教学模式在医科院校医用化学教学中的应用与思考

医用化学是医学院校一门重要的基础必修课程,内容多为知识理解型,这导致了学生兴趣薄弱,学习效果欠佳。因此,需要通过改革传统"灌输式"课堂授课方式,让学生真正参与到教学活动中。BOPPPS教学模式分为导言、学习目标、前测、参与式学习、后测和总结六个环节。突出"以学生为中心"的教学理念,遵循教学活动的客观规律。在医用化学课程的教学过程中引入BOPPPS教学,能够有效提高学生的课堂参与度,增强学生的学习动力,培养学生独立思考、自主学习的能力。