放射治疗记录与验证系统质量控制指南

放疗记录与验证系统(RVS)是一套用于防止医用电子加速器等放疗设备治疗参数设置错误,并且记录所有放疗阶段执行参数的医用计算机软件控制系统。为确保患者的治疗安全,必须对记录与验证系统采取必要的质量控制措施。本指南内容涉及:RVS安装和参数设定过程中的质量控制;RVS的验收测试;RVS在临床使用过程中的持续质量控制;使用RVS过程中的典型错误类型;执行RVS验收测试的具体测试例。     

Comparative study of mucoadhesive and mucus-penetrative nanoparticles based on phospholipid complex to overcome the mucus barrier for inhaled delivery of baicalein

Efficient mucosal delivery remains a major challenge for the reason of the respiratory tract mucus act as a formidable barrier to nanocarriers by trapping and clearing foreign particulates. The surface property of nanoparticles determines their retention and penetration ability within the respiratory tract mucus. However, the interaction between nanoparticles and mucus, and how these interactions impact distribution has not been extensively investigated. In this study, polymeric nanoparticles loaded with a baicalein–phospholipid complex were modified with two kinds of polymers, mucoadhesive and mucus-penetrative polymer. Systematic investigations on the physicochemical property, mucus penetration, transepithelial transport, and tissue distribution were performed to evaluate the interaction of nanoparticles with the respiratory tract. Both nanoparticles had a similar particle size and good biocompatibility, exhibited a sustained-release profile, but showed a considerable difference in zeta potential. Interestingly, mucus-penetrative nanoparticles exhibited a higher diffusion rate in mucus, deeper penetration across the mucus layer, enhanced in vitro cellular uptake, increased drug distribution in airways, and superior local distribution and bioavailability as compared to mucoadhesive nanoparticles. These results indicate the potential of mucus-penetrative nanoparticles in design of a rational delivery system to improve the efficiency of inhaled therapy by promoting mucus penetration and increasing local distribution and bioavailability.     

基于核心能力的临床医学专业研究生课程体系建设研究

临床医学专业研究生课程体系是培养研究生过程中极为重要的环节，课程是实现教育教学目标的关键载体和平台。目前，我国对于临床医学教育提出了创新改革课程体系的具体要求。2019年我国教育部发布了《教育部卫生部关于加强医学教育工作提高医学教育质量的若干意见》，表示各大医学高校要“积极全面开展课程体系革新，使得医学知识与自然科学和人文科学知识的融合”。突出学生的教学主体性，创建学生为中心的专业教学模式，大力促进教学方法的创新和实践，强化学生综合知识能力、创新意识以及批判性思维的培养和锻炼。本文对基于核心能力的临床医学专业研究生课程体系建设进行研究，并提出具体的建设策略，以期为我国临床医学专业研究生培养提供有价值的参考建议。     

穴位贴敷联合风咳汤治疗感染后咳嗽的临床研究

目的:探究风咳汤联合穴位贴敷治疗感染后咳嗽的临床疗效,以期丰富治疗方法,为治疗感染后咳嗽提供科学依据。方法:选取2017年1月至2018年1月南京市中西医结合医院收治的感染后咳嗽患者88例作为研究对象,按照随机数字表法随机分为对照组和观察组,每组44例。对照组予常规治疗,观察组在对照组基础上加用风咳汤联合穴位贴敷治疗,均治疗2周。观察比较2组患者采用不同方法治疗前、后中医证候积分、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)、诱导痰上清液中P物质(SP)含量水平变化情况。治疗过程中收集不良反应资料,结束治疗后比较2组疗效。结果:1)2组患者完成治疗方案后,中医症候积分较治疗前均显著下降,观察组显著优于对照组,差异有统计学意义(P<0.05);2)治疗后2组患者IL-8、TNF-α、SP含量均较治疗前显著下降,且观察组优于对照组,差异有统计学意义(P<0.05);3)观察组患者临床控制率、总有效率明显高于对照组,差异有统计学意义(P<0.05)。4)2组患者ALT、AST、CCr、BUN水平和不良反应发生率比较,差异无统计学意义(P>0.05)。结论:风咳汤联合穴位贴敷治疗感染后咳嗽能提高疗效,降低炎性反应水平,改善症状和生命质量。     

Basic fibroblast growth factor promotes doxorubicin resistance in chondrosarcoma cells by affecting XRCC5 expression

Chondrosarcoma is the second most common form of bone cancer and is characterized by its ability to produce an extracellular matrix of the cartilage. High-grade chondrosarcoma is highly aggressive and can metastasize to other parts of the body. Chondrosarcoma is resistant to both conventional chemotherapy and radiotherapy; hence, the current main treatment is still surgical resection. Doxorubicin (Dox) has been shown to significantly improve patient survival compared with untreated chondrosarcoma. However, for patients with metastasis, surgical resection alone can hardly treat them. In addition, drug resistance is one of the leading causes of death in patients with chondrosarcoma. Secreted proteins can mediate cell-cell interactions in the cancer microenvironment, which may be associated with the development of drug resistance. In the present study, chondrosarcoma cells were treated with Dox, the conditioned medium was then collected and changes in secreted proteins were analyzed using the antibody array. Results showed that the Dox-treated group had the highest secretion of basic fibroblast growth factor (bFGF), indicating the effect of bFGF on Dox sensitivity in chondrosarcoma. Furthermore, lentiviral-mediated knockdown and treatment of exogenous recombinant protein were employed to further investigate the effect of bFGF on Dox resistance. Results demonstrated that bFGF can promote the expression of X-ray repair cross-complementing protein 5 (XRCC5), leading to Dox resistance. Secreted bFGF is likely to be detected in serum, in addition to being a biomarker for predicting Dox resistance, the combination of Dox and bFGF/XRCC5 blockers may be a new therapeutic strategy to improve the efficacy of Dox in future.     

单抗N糖分析系统适用性对照品的建立

目的建立单抗N糖分析方法的系统适用性对照品,并设定相应的系统适用性要求。方法利用液质联用(LC-MS)仪对N糖系统适用性对照品进行N糖型的表征鉴别,并对对照品进行稳定性评价。结合方法特点和验证数据,对系统适用性要求进行设定。结果建立的系统适用性对照品具有良好的稳定性,其糖型涵盖了单抗主要的N糖型种类。针对3种药典拟收录的单抗N糖分析方法,设定了以下系统适用性要求,包括:图谱与典型图谱相似、G1F(1,6)和G1F(1,3)的分离度应满足具体要求、G0F%应在规定的范围内、G0F保留时间的RSD应≤4%。结论建立了单抗N糖系统适用性对照品,可配合3种2020年版《中国药典》拟收录的N糖分析方法使用。     

Reflection of neuroblastoma intratumor heterogeneity in the new OHC-NB1 disease model

Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC-NB1, from a bone marrow metastasis from a patient diagnosed with MYCN-amplified neuroblastoma and performed whole-exome sequencing on the source metastasis and the different models and passages during model development (monolayer cell line, 3D spheroid culture and subcutaneous xenograft tumors propagated in mice). OHC-NB1 harbors a MYCN amplification in double minutes, 1p deletion, 17q gain and diploid karyotype, which persisted in all models. A total of 80–540 single-nucleotide variants (SNVs) was detected in each sample, and comparisons between the source metastasis and models identified 34 of 80 somatic SNVs to be propagated in the models. Clonal reconstruction using the combined copy number and SNV data revealed marked clonal heterogeneity in the originating metastasis, with four clones being reflected in the model systems. The set of OHC-NB1 models represents 43% of somatic SNVs and 23% of the cellularity in the originating metastasis with varying clonal compositions, indicating that heterogeneity is partially preserved in our model system.     

Immunotherapy in Hodgkin and non-Hodgkin lymphoma: Innate,adaptive and targeted immunological strategies

Since the clinical introduction of anti-CD20 monoclonal antibodies into lymphoma treatment, immunologic approaches in lymphoma have made substantial progress. Advances in our understanding of tumor immunology have led to the development of strategies to overcome immunologic barriers responsible for an ineffective immune response. Specifically, therapeutic agents have been developed and tested against molecules that are responsible for T-cell exhaustion. The use of monoclonal antibodies against immune checkpoints in the adaptive immune system, such as programmed cell death-1 and cytotoxic T-lymphocyte-associated protein 4, has changed the landscape of cancer therapy including the treatment of lymphoma. This achievement has recently been accompanied by the development of novel immune checkpoint inhibitors targeting the innate immune system, including the CD47-SIRPα signaling pathway, and this approach has yielded promising results. To overcome impaired antigen presentation, antibody-based cytotoxic strategies, namely antibody-drug conjugates (polatuzumab vedotin and brentuximab vedotin) and bispecific T-cell or NK-cell engagers (blinatumomab, REGN1979, RG6206, and AFM13), have rapidly evolved with promising clinical activity. As additional tools become available for lymphoma treatment, formulation of safe, rational combination strategies to combine them with standard therapy will be of paramount importance. A successful approach to the treatment of lymphoma may require both an optimized anti-tumor immune response as well as effective depletion of malignant lymphoid cells.