编者按

      生物安全二级实验室（BSL-2/ABSL-2 实验室）是开展第三类病原微生物实验活动以及第二类病原微生物的样本检测和未经培养的感染材料操作所必需的生物安全实验室。

      2023 年 6 月 29 日，《生物安全二级实验室运行管理通用要求》团体标准在中国医药生物技术协会批准立项。中国医药生物技术协会生物安全专业委员会于 2023 年 10 月 8 日成立标准编制组，正式启动团体标准编制工作。

      按照《中华人民共和国生物安全法》和国务院 424 号令《病原微生物实验室管理条例》的要求，病原微生物实验室的设立单位负责实验室的生物安全管理，制订科学、严格的管理制度，定期对有关生物安全规定的落实情况进行检查。《生物安全二级实验室运行管理通用要求》对指导实验室设立单位或机构对生物安全二级实验室的日常运行管理工作制订一套完整的管理程序和措施，更好地保障生物安全二级实验室的标准化运行和管理是非常必要的。

      标准编制组通过搜集整理国内外相关行业规范、文献和相关标准，开展系列研究工作，分析相关信息，形成了《生物安全二级实验室运行管理通用要求》的编写内容；标准编制组结合我国国情，确定了以病原微生物安全二级实验室为编制对象，以运行要求为技术导向，以实验室运行管理为编制原则和技术框架。标准编制过程中共收到 12 家单位 60 条修改意见和建议，编制组经过汇总、梳理，采纳意见 55 条，部分采纳 4 条，不采纳意见 1 条。编制组对征求的意见进行了研讨和分析，对《生物安全二级实验室运行管理通用要求》进行修改和补充完善。经过协会标准工作委员会审定、公示等程序，《生物安全二级实验室运行管理通用要求》于 2024 年 7 月 3 日发布并实施。

      《生物安全二级实验室运行管理通用要求》是现行有效的法律法规和技术标准与病原微生物实验室活动和管理具体实践的结合，有助于规范生物安全二级实验室运行管理文件的编制和信息统一，提升生物安全二级实验室运行管理的标准化。需要说明的是，本标准是针对人间传染的病原微生物为对象的生物安全二级实验室运行管理的指南。

      来自病原微生物、实验动物、流行病学、检验检疫、医院临床检验、实验室建设和管理等领域的二十多位专家学者，以及中国医药生物技术协会和中国医药生物技术协会生物安全专业委员会的数十家从事病原微生物研究、检验检测和生物制品研发生产等会员单位参加了本标准的编制工作，在此一并致谢。

Traditional Chinese Medicine (TCM) hospital preparations, as clinical formulas that address unmet clinical needs not met by marketed drugs, hold significant research and development value and potential. This article aims to explore how to leverage the unique advantages of hospital preparations to accelerate their transformation into new TCM drugs. The article provides a thorough analysis of the current management requirements and characteristics of hospital preparations and, based on this analysis, identifies directions for improvement in new drug research and development transformation. In conjunction with the active support of national policies, this article proposes a set of strategies that fully utilize the human experience of hospital preparations to shorten the research and development process and investment, with the goal of promoting the rapid transformation of TCM hospital preparations into new drugs for market launch and further advancing the inheritance and development of TCM.

目的  建立自然杀伤细胞（NK 细胞）体外杀伤活性检测方法并进行验证。

方法  以慢性髓源白血病细胞 K562 为靶细胞，使用 5(6)-羧基二乙酸荧光素琥珀酰亚胺酯（CFDA SE）标记后，将携带 CFSE 荧光的靶细胞按照不同的效靶比与 NK 细胞共培养。使用死细胞染料碘化丙啶（PI）与早期凋亡染料 Annexin V 对共培养的细胞进行染色后，采用流式细胞仪对 CFSE 荧光筛对靶细胞圈门，同步圈门 PI 检测其死亡率与 Annexin V 检测早期凋亡率，计算杀伤率。对活细胞染料 CFDA SE 与死细胞染料 PI 及早期凋亡染料 Annexin V 使用量、检测限与定量限、准确度、重复性、再现性进行验证。

结果  经过活细胞染料 CFDA SE 用量验证后，2 × 10⁶ 个K562 靶细胞的 CFDA SE 最佳使用量为 0.2 μL。PI 与 Annexin V 的最佳使用量均为 1 μL/Test。靶细胞死亡与早期凋亡检出限为 0.1%，定量限为 0.5%。准确度、重复性、再现性验证结果均能满足 YY/T 0588《流式细胞仪》中表面标志物检测的重复性 a) 阳性百分比 ≥ 30% 时，CV 值应 ≤ 8%；或 b) 阳性百分比 < 30% 时，CV 值应 ≤ 15% 的要求。t 值与理论值符合 95% 置信水平中的统计学要求。

结论  建立的 NK 细胞体外杀伤活性检测方法符合标准化评价体系，为 NK 细胞功能检测与质量评价提供了参考依据。

Synthetic biology is an emerging interdisciplinary discipline that combines engineering and science. Synthetic biology, which can modify or create living organisms, is making a huge difference in many fields and helping to address challenges in medicine, agriculture, manufacturing, and the environment for the great benefit of humankind. However, as a dual-use discipline, synthetic biology is also characterized by potential biosafety and biosecurity risks due to its complexity and uncertainty, making it difficult to biosafety management. The article describes the rapid development of synthetic biology and the urgent biosafety issues it raises, explains the importance of risk assessment in the biosafety management of synthetic biology R&D activities, and then proposes for the first time the idea of categorizing and hierarchical management of the biological risks of synthetic biology R&D activities and related targeted recommendations.

When evaluating the operational activities of high-grade biosafety laboratories, common issues often arise regarding the management of highly pathogenic microorganisms (viruses) and specimens. With the support of the National Health Committee, the Biosafety Professional Committee of the China Medical Biotechnology Association organized an expert seminar inBeijingto address these issues. The seminar focused on two common problems: "dual-person dual-lock" and "life-cycle information management". Experts thoroughly discussed the implementation of the "dual-person dual-lock" system and the management of life-cycle information, considering technical feasibility and specific content in the era of innovative technology. Consensus was reached among experts on the implementation of specific technologies and management modes to address expert consensus.

Drug target is a key in drug discovery. Although cells have over 30000 proteins, for particular cellular function only few of the proteins are critical. The biological role of the critical proteins could be described as “head goose effect”, and these molecules could be called “head goose molecules (HGMs)”. We assume that under the support from intra- or extra-cellular circumstances the HGMs could be regulated by drugs, then release instructive signals (for instance, protein modification) to other proteins. Through proper cooperation of the HGMs with other protein molecules the disease cell could be reprogrammed, yielding safe and therapeutic effects. Therefore, HGMs might be the best drug targets. Here, we show good HGM examples in energy metabolism, and drugs that target the metabolic HGMs are quite successful in clinic. We hope the thought interest for those working on drug target discovery.

In recent years, cell therapy, including stem cell therapy and immune cell therapy, has emerged as an innovative treatment technology that has attracted significant attention. It provides new hope for patients with cancer, degenerative diseases, and other serious illnesses. With the rapid advancement of cell therapy technology, the industrialization of cell products has become a key focus for both current and future development. This paper gives an overview of regulatory policies, the structure of the industrial chain, the current status of industrialization efforts in the field of cell therapy, and identifies challenges faced during industrial development along with potential solutions. Additionally, it highlights the importance of enhancing product accessibility through universal off-the-shelf products and improving quality uniformity through automation and large-scale production to facilitate the industrialization process, with the support of cell biology, artificial intelligence, and Internet of Things technology. Finally, this paper offers a forward-looking perspective on the future direction of industrial development in cell therapy.

From fat transplantation, bone disease, cartilage disease to skin repair, the clinical trails of stromal vascular fraction (SVF) involve many fields and have achieved beneficial results. Since fat SVF is a multi-cell heterogeneous group of cells, it can play a vital role in the field of regenerative medicine with effects on tissue repair, immune regulation, and angiogenesis promotion. Compared to traditional stem cell therapy, it can comprehensively and systematically repair damaged tissues. Fat SVF has shown beneficial results in cartilage repair and assisted transplantation, and has become one choice in the treatment of osteoarthritis and osteonecrosis of the femoral head. Compared with other cell therapies, fat SVF follows the principle of minimum operation in vitro and is safer. Currently, the main type of SVF used in clinical treatment is obtained by enzymatic digestion. The SVF obtained by this method consists of pure cell components, enhancing the performance of cells in their respective functions and conducive to quality control and supervision. This article reviews recent clinical cases involving fat SVF and discusses the route of administration, dosage, therapeutic effects, and etc. However, the problems such as relatively few cases available, the short observation period for safety assessment, and the lack of thorough research on its treatment mechanisms, need to be addressed before introducing SVF into clinical treatment.

Objective  To establish an analytical ultracentrifugation method for measuring the size variants of monoclonal antibodies (mAb).

Methods  By optimizing key indicators such as rotational speed, temperature, and data analysis parameters, a method for measuring the size variants of mAbs was developed. The specificity, repeatability, precision, and linearity of this method were validated.

Results  The optimized experimental conditions were as follows: rotational speed at 50 000 r/min, temperature at20℃, analysis parameter resolution at 150, and s max at 20. Method validation results showed that the relative standard deviation (RSD) of six repeatability experiments was 0.91%, overall precision RSD was 0.78%, and the method demonstrated good linearity in the concentration range of 0.2 - 0.8 mg/mL.

Conclusion  The analytical ultracentrifugation method demonstrated good specificity, repeatability, precision, and linearity, making it suitable for determining the size variants of monoclonal antibodies.

Cancer has become one of the main causes of global human mortality, posing a significant threat to the lives and health of many patients. While radiotherapy and chemotherapy are the primary treatment modalities for most patients, they are often associated with limitations and serious side effects, highlighting the need for new strategies in cancer treatment. Antibody-based proteins have emerged as an important class of biological therapies, primarily due to the stability, specificity, and adaptability of the antibody framework. Antibodies possess inherent binding capabilities to antigens and endogenous immune receptors, leading to the development of various monoclonal antibody (mAb) derivatives such as bispecific antibodies, antibody-drug conjugates, and antibody fragments, which have shown efficacy in treating human diseases, particularly in oncology. Based on the structure and function of antibodies, this review focuses on the research and treatment status of monoclonal antibodies, antibody-drug conjugate and bispecific antibodies.

Objective  To identify potential small-molecule lead compounds with anti-atherosclerotic activity by establishing a high-throughput screening model, targeting the transcriptional level of human perilipin-2 (PLIN2).

Methods  A recombinant plasmid pGL4-PLIN2p containing the human PLIN2 gene promoter region was constructed and transfected into HepG2 cells. A stable transfected cell line, PLIN2p-Luc HepG2, was obtained through G418 resistance selection. The stable cell model was then optimized and evaluated, followed by large-scale screening to identify active compounds. The effects of these compounds on Plin2 mRNA and protein expression, as well as lipid droplet formation in foam cells, were further assessed using qRT-PCR, Western blot, and oil red O staining.

Results  A stable cell line, PLIN2p-Luc HepG2, containing the human PLIN2 promoter sequence was successfully established, satisfying the requirements for high-throughput screening. Over 8000 compounds were screened using the PLIN2p-Luc HepG2 cell line, and after initial and secondary screenings, six active compounds were identified and showed apparent dose-response relationships. Among them, compound MK8722 dose-dependently inhibited the Plin2 mRNA and protein expression in foam cells and significantly reduced intracellular lipid droplet formation.

Conclusion  A stable cell line, PLIN2p-Luc HepG2, suitable for high-throughput screening of inhibitors, is established, and the active compound MK8722 is identified. This study provides new insights and research methods for discovering anti-atherosclerosis drugs based on lipid droplets.

The article highlights the continuous improvement of China's legislative and regulatory framework for biosecurity amidst the rapid development of biological products, particularly following the enforcement of the "Biosafety Law of the People's Republic of China," which has bolstered biosafety management. It explores the establishment of a biosecurity defense line in the regulation of biological products inChina, examining the requirements for biosafety management, challenges faced, and strategies for preventive control. Utilizing regulatory analysis and literature research, the article identifies risk factors in biosafety management of biological products and suggests corresponding management strategies. It emphasizes the importance of defining the primary responsibilities of relevant entities in biological product development, strengthening management of crucial research and production stages, and establishing collaborative regulatory mechanisms between oversight agencies to enhance biosafety management. The article concludes with recommendations to enhance legislation and regulations, improve education and training, and bolster regulatory capacities to advance biosafety management inChina's biological products, ensuring product quality and safety, as well as safeguarding public health.

Objective  To establish a reverse transcriptase activity assay for the detection of replication-competent lentivirus (RCL) and to validate the methodology.

Methods  The RNA of bacteriophage MS2 served as a template for reverse transcription, with specific amplification signals detected via TaqMan-based quantitative Real-time PCR (qPCR). Moloney murine leukemia virus reverse transcriptase (M-MLVRT) was used as a standard for quantitative assay by plotting a standard curve. Methodological parameters, including specificity, dynamic range, precision, repeatability, intermediate precision, limit of quantification, limit of detection, robustness and applicability were validated.

Results  Through the optimization of primers, probe concentration, and reaction conditions, a stable and sensitive assay for reverse transcriptase activity was established, demonstrating high specificity and non-specific amplification across four types of cell supernatant samples. The assay exhibited a wide linear range from 10⁴ to 10⁹ pU/μL, with r² value higher than 0.99, and the amplification efficiency ranged from 93% to 97%. The accuracy (rate of recovery) fell between 86% and 102%, with repeatability (relative standard deviation, RSD) less than or equal to 6%. Intermediate precision and robustness RSD were less than or equal to 4% and 8%, respectively, and robustness recovery ranged from 89% to 105%. The limit of quantification (LOQ) and limit of detection (LOD) were determined as 8000 pU/μL and 100 pU/test, respectively. Reverse transcriptase activity was successfully detected in the terminal stage samples of three cell culture assay types - CAR-T cells, end of production cell (EOPC), and unprocessed bulk (UPB) - as well as their virus-infected samples. Notably, no activity was detected in the three sample types without virus infection, while the virus-infected spiked samples were successfully detected.

Conclusions  The reverse transcriptase activity-based RCL assay was successfully established, with all validation results meeting detection requirements. It is suitable for detecting terminal stage samples in cell culture assays, providing technical support for the safe application of gene therapy products.

Vaccines are one of the most important tools for combating infectious diseases. A variety of novel vaccines have been developed to enhance the immunogenicity and safety of vaccines. Viral vectors, as an important gene manipulation tool in biological research, are a good platform for vaccine delivery. They mimic viral structures and physiological features, stimulating cellular and humoral immunity while also activating innate and mucosal immune responses, ultimately improving vaccine immunogenicity. Genetic modifications further enhance the safety of viral vectors. This article discusses the main properties of viral vectors currently used in vaccine development and reviews vaccines designed using these platforms, with the aim of providing references and insights for the development of viral vector vaccines.

编者按

临床研究中心（CRU）是医疗卫生机构成立的，为院内研究者开展临床研究提供专业技术支持、实施规范化管理和统筹协调研究资源的专门部门。CRU 的建设是完善临床研究管理体系和管理机制、提高我国临床研究能力的重要基础。

2021 年，《临床研究中心建设与管理规范》团体标准在中国医药生物技术协会批准立项。中国医药生物技术协会临床研究专业委员会于 2021年 4 月成立标准编制组，正式启动团体标准编制工作。

当前，我国临床研究体系建设仍面临诸多挑战，在管理体系、组织架构、人才储备和基础设施等方面存在明显短板，这些问题已成为制约临床研究高质量发展的重要瓶颈。究其根本，主要表现在以下几个方面：其一，国家层面尚缺乏统一的 CRU 建设标准规范，导致研究设计、过程监管和成果转化等关键环节缺乏系统性指导；其二，研究者发起研究与企业发起研究之间协同不足，医疗机构内部 CRU 的建设缺乏科学合理的顶层规划；其三，研究人员准入标准参差不齐，专业技术人才储备不足，加之部分研究者对 GCP 规范理解不深，临床试验设计水平和质量控制能力亟待提升；其四，支撑临床研究的软硬件基础设施尚未形成标准化体系。这些深层次问题直接影响了我国临床研究的整体质量，表现为高质量临床研究产出不足、研究成果转化效率低下，以及在国际学术界缺乏具有影响力的“中国方案”和“中国证据”。《临床研究中心建设与管理规范》对临床研究中心的建设与管理制订一套完整的管理程序和措施，更好地保障了临床研究中心的标准化运行和管理。

标准编制组通过搜集整理国内外相关行业规范、文献和相关标准，开展系列研究工作，分析相关信息，形成了《临床研究中心建设与管理规范》的编写内容；标准编制组结合我国国情，确定了 CRU 的范围、规范性引用文本、术语和定义、功能、组织架构、人员配置、基础设施、管理制度、评估和附录等 10 部分内容。标准编制过程中共收到 16 家单位 73 条修改意见和建议，编制组经过汇总、梳理，采纳意见 18 条，部分采纳 22 条，不采纳意见 33 条。编制组对征求的意见进行了研讨和分析，对《临床研究中心建设与管理规范》进行修改和补充完善。经过协会标准工作委员会审定、公示等程序，《临床研究中心建设与管理规范》于 2024 年5 月6 日发布并实施。

《临床研究中心建设与管理规范》的制订与实施具有重要的现实意义。该规范着眼于构建标准化的临床研究管理体系，通过明确临床研究中心实体机构的建设标准，建立健全覆盖项目全流程的管理制度，严格遵循国家法律法规和伦理准则，系统性地完善临床研究的组织架构和运行机制。相信该规范的出台，将为提升我国临床研究质量、增强国际学术竞争力提供有力的制度保障，对推动我国临床研究事业高质量发展具有重要意义

来自临床研究方法学、临床研究管理、医学伦理等领域的二十多位专家学者，以及中国医药生物技术协会和中国医药生物技术协会临床研究专业委员会的数十家从事临床研究管理以及临床研究方法学研究的会员单位参加了本标准的编制工作，在此一并致谢。

Objective  To investigate the anti-tumor effects of Erigeron breviscapus injection (EBI) on hepatocellular carcinoma (HCC) both in vitro and in vivo, and to elucidate the underlying mechanisms related to the mitochondrial apoptosis pathway.

Methods  Human HCC cell lines HCCLM3, Huh7, and HepG2 were cultured and treated with various concentrations of EBI. Cell viability was assessed using the CCK-8 assay, while cell death was evaluated through Calcein AM/PI live/dead staining. The migration ability of the cells was determined using the Transwell migration assay. Western blot analysis was performed to detect the expression levels of mitochondrial apoptosis-related proteins, including Bcl-2, Bax, and caspase-3. An in vivo high-metastatic HCCLM3 subcutaneous xenograft model was established to compare tumor growth and liver metastasis between EBI-treated and control groups.

Results  The data from CCK-8 assays demonstrated that EBI inhibited the proliferation of HCCLM3, Huh7, and HepG2 cells in a dose-dependent manner, with IC₅₀ values of 81.41, 177.90, and 209.70 μg/mL, respectively. Live/dead staining results indicated that EBI promoted cell death in HCCLM3 cells in a concentration-dependent manner. EBI also significantly reduced the migration ability of HCC cells in a dose-dependent manner through Transwell migration assays. The results from Western blot analysis showed that EBI decreased the expression of the anti-apoptotic protein Bcl-2, increased the expression of the pro-apoptotic protein Bax, and reduced the expression of the precursor of cleaved caspase-3, suggesting the activation of the mitochondrial apoptosis pathway. Furthermore, EBI significantly inhibited the growth of HCCLM3 xenografts and reduced liver metastasis.

Conclusion  EBI exhibits significant anti-tumor effects on hepatocellular carcinoma both in vitro and in vivo. The underlying mechanism is likely through the activation of the mitochondrial apoptosis pathway. These findings support the potential of EBI as a novel therapeutic agent for HCC and provide a foundation for future clinical applications.

Objective  To explore the therapeutic effect and possible regulatory mechanisms of umbilical cord mesenchymal stem cell transplantation in treating lung injury in newborn rats induced by high oxygen levels.

Methods  Mesenchymal stem cells were isolated from human umbilical cord and cultured in vitro. The cell phenotype was identified by flow cytometry. 36 newborn rats were randomly divided into three groups: control group, model group, and model + MSC treatment group. Except for the control group, the remaining two groups of rats were raised in a high-pressure oxygen chamber to establish a lung injury model. The control group was raised in indoor air. After 4 days of modeling, the model + MSC treatment group received cell injection, while the control group and model group received saline injection. 2 weeks later, the newborn rats were euthanized, and the wet/dry weight ratio of lung tissue in each group was measured. The pathological changes, vascular muscular changes, and microvascular density of lung tissue in each group were observed by tissue sectioning staining. The levels of ROS and MPO activity, MDA, IL-6, IL-1β, and TNF-α expression in the tissues of each group were also measured.

Results  Compared with the control group of newborn rats, the wet/dry weight ratio of lung tissues, ROS activity, MPO activity, MDA content, and expression levels of inflammatory factors IL-6, IL-1β, and TNF-α were all increased in the model group of neoborn rats, indicating successful modeling. Compared with the model group, the wet/dry weight ratio of lung tissues, ROS activity, MPO activity, MDA content, and expression levels of inflammatory factors IL-6, IL-1β, and TNF-α were all decreased in the model+MSC treatment group. Lung tissue edema and inflammatory cells infiltration were significantly better than those in the model group, and the degree of vascular muscularization was significantly reduced with a significant increase in microvascular density.

Conclusion  UC-MSC can significantly improve lung injury in newborn rats induced by high oxygen levels and have a certain reparative effect.

Objective  To study the biodistribution of human umbilical cord mesenchymal stem cells in normal C57BL/6J mice and experimental autoimmune encephalomyelitis mice, a model of multiple sclerosis.

Methods  Human umbilical cord mesenchymal stem cells were labelled using the DiR near-infrared fluorescent dye labeling technique and infused back into normal C57BL/6J mice and experimental autoimmune encephalomyelitis mice. Live imaging was performed to trace the stem cells at 2 h, 3 h, 1 d, 3 d, 5 d, 7 d, 10 d, and 14 d after administration of the stem cells. Mice were sacrificed after 14 d and tissue imaging of heart, liver, spleen, lung, brain, and spine (including spinal cord) was performed.

Results  After DiR-labelled human umbilical cord mesenchymal stem cells were given to mice by intravenous, the mesenchymal stem cells showed a tendency of increasing and then decreasing in vivo, reaching a peak at day2 innormal C57BL/6J mice and day1 indisease model mice. Fluorescent signals were undetectable at day10 innormal C57BL/6J mice, and still detectable at day10 indisease model mice, and undetectable at day 14. In the normal animals, the cells were not detected for day 10, and were still detectable for day14 inmodel mice. The results from tissue imaging studies showed that after a single tail vein administration of stem cells to normal C57BL/6J and disease model mice, the cells survived for at least 14 days in vivo, and concentrated in the lung, liver and spleen.

Conclusions  Human umbilical cord mesenchymal stem cells survive for at least 14 days in normal C57BL/6J mice and experimental autoimmune encephalomyelitis mice after intravenous administration, mainly homing to the lungs, liver and spleen, etc. Human umbilical cord mesenchymal stem cells may survive longer in experimental autoimmune encephalomyelitis disease mice, a model of multiple sclerosis, than in normal C57BL/6J animals. And human umbilical cord mesenchymal stem cells have a more pronounced splenic homing effect experimental autoimmune encephalomyelitis disease mice.

目的  量化评价我国人类遗传资源管理政策，探究政策发展规律和现存问题，为后续政策的制定和完善提供参考。

方法  对我国现有的 4 个人类遗传资源管理政策进行文本挖掘，使用词云图展示高频词汇，用社会网络描述高频词间的关联，再结合国外人类遗传资源管理政策构建 PMC 指数模型，包含 10 个一级变量和 49 个二级变量。使用该模型对政策进行量化分析。

结果  我国人类遗传资源管理政策取得了长足进步，最新政策的 PMC 评分已达国际先进水平，总体规划较为合理，但还有需要完善的地方。

结论  我国人类遗传资源管理政策发展迅速，可以满足当前形势下人类遗传政策管理需求。但仍存在部分定义模糊，缺少配套文件，缺少人才培养规范等问题，需要进一步完善政策以充分保护、利用我国人类遗传资源，推动我国和世界卫生健康事业发展。

While high-level biosafety laboratories are rapidly developing into large scale and diversified businesses, archives and records management needs to keep pace with the development of the laboratory, and it becomes urgent and important to explore an archive management model suitable for the current and future development needs. Based on comprehensively analyzing the management models of high-level biosafety laboratories and practical management experiences, the article summarizes a set of diversified and accurate lifecycle management models suitable for the management of archives and records of the laboratories. The models cover the construction of archives, the summary and analysis of the entire lifecycle of archives and records, including compilation, collection, identification, cataloging, storage, research, and utilization, and formulate a modern and diversified accurate management strategies for each stage, taking into account the requirements of accuracy, authenticity, integrity and accessibility of archives and records. From the three aspects of hierarchical, graded, and decentralized management, we ensure the standardization, uniformity, and precision of the management process, thereby enhancing the smooth development of scientific research integrity, supervision and inspection, qualification authentication, and activity review.

Objective  The goal of this study was to create dasatinib-loaded biomimetic exosomes and assess their properties and effectiveness in treating lung cancer.

Methods  Dasatinib-loaded biomimetic exosomes were prepared by merging exosomes derived from human lung cancer H460 cells with drug-loaded liposomes through membrane fusion and self-assembly. The particle size and zeta potential were measured using dynamic light scattering (DLS). The successful fusion of exosomes and liposomes was verified via Western blot and fluorescence resonance energy transfer (FRET) assay. Cellular uptake was quantitatively analyzed using fluorescent probe-based imaging. The

in vitro cytotoxicity was assessed by MTS assay, while in vivo tumor targeting, anti-tumor efficacy, and safety were evaluated in subcutaneous tumor-bearing mice through fluorescent imaging and pharmacological studies.

Results  The dasatinib-loaded biomimetic exosomes exhibited a particle size of (111.3 ± 0.1) nm and a zeta potential of (–30.1 ±

0.3) mV. Western blot confirmed the expression of exosomal markers (CD9, CD81, OXER1) on the biomimetic exosomes. The FRET assay revealed a membrane fusion index of 2.171 ± 0.044, indicating efficient fusion between exosomes and drug-loaded liposomes. Fluorescent imaging demonstrated significantly higher uptake of biomimetic exosomes by homologous lung cancer cells compared to liposomes (P < 0.05), with no significant difference observed in heterologous pancreatic cancer cells. The biomimetic exosomes exhibited markedly enhanced cytotoxicity in vitro compared to free dasatinib and liposomal formulations. In vivo studies demonstrated superior tumor accumulation (homing ability), a tumor inhibition rate of 75.0%, and no significant weight loss in mice during treatment.

Conclusion  Dasatinib-loaded biomimetic exosomes display potent anti-lung cancer activity with favorable safety profiles, suggesting their potential as a therapeutic option for non-small cell lung cancer.

The rapid development of the biopharmaceutical industry has led to the introduction of numerous new technologies and products, posing challenges to the assessment of their viral safety. To address the viral safety control strategy and validation of viral clearance for biologics in this new situation, this paper reviews studies on viral vector-based products, continuous manufacturing process and the utilization of prior knowledge and platform validation in accordance with the updated viral safety guideline for biologics. It compares the viral safety control strategies of viral vector-based products with traditional recombinant products, as well as the differences between continuous manufacturing processes and traditional batch production. Furthermore, it discusses the application of prior knowledge and platform validation strategy versus the traditional viral clearance validation strategy. Recommendations are made for viral safety control strategies and the implementation of virus clearance validation in the new environment, offering guidance for researchers, manufacturing companies, and regulatory bodies.

Objective  To study the properties of hydrogels loaded with extracellular vesicles derived from human adipose mesenchymal stem cells and its role in healing of diabetic ulcer.

Methods  Poloxamer 407 and hydroxypropyl methylcellulose were used as excipients to prepare controlled-release, temperature-sensitive hydrogels loaded with extracellular vesicles (EVs) derived from human adipose mesenchymal stem cell (haMSC). The properties of the hydrogel were studied, and the wound area of db/db diabetic mice was smeared locally with hydrogels to explore the applicability and therapeutic effect on diabetic wounds.

Results  The extracellular vesicles were isolated from human allogenic adipose mesenchymal stem cell conditioned medium, and the final concentration of Poloxamer 407 and hydroxypropyl methylcellulose was 20% and 0.5%, respectively. Hydrogels showed good thermosensitive properties, the gelling temperature was about26.0 ℃, and the gelling time was about 1 minute and 30 seconds. In addition, hydrogels showed proper strength and adhesion for clinical use. The results from in vitro release test showed that the cumulative amount of extracellular vesicles from hydrogels had a good linear relationship with time, and the gel showed good protective and controlled release effects of extracellular vesicles in uptake experiment. At the same time, the data from in vivo experiments showed that extracellular vesicle hydrogels significantly promoted the re-epithelialization of diabetic wound in db/db mice, alleviated the infiltration of dermal and subcutaneous inflammatory cells, improved the arrangement of collagen fibers, thereby promoted the healing of diabetic wound.

Conclusion  The thermosensitive hydrogels prepared by Poloxamer 407 and hydroxypropyl methylcellulose has a good protective and controlled release effect on haMSC-EVs, and can promote wound healing in diabetic mice.

目的  研究不同试验体系中组氨酸含量对鼠伤寒沙门氏菌回复突变菌落数背景值的影响。

方法  选择药品和食品安全性评价中常用的鼠伤寒沙门氏菌 TA97a、TA98、TA100、TA1535 和 TA1537，分别在非代谢活化和代谢活化条件下开展基于 6 孔板（mini-Ames 试验，组氨酸浓度范围为 0.03 ~ 1 mg/mL）和标准平皿 Ames 试验（组氨酸浓度范围为 0.01 ~ 0.5 mg/mL）。

结果  Mini-Ames 试验中组氨酸浓度在 0.2 ~ 0.3 mg/mL 范围内时，TA98、TA100 和 TA1535 在无或有 S9 条件下的回复菌落数与溶媒对照组相比增加 2 倍或 3 倍以上，呈阳性结果。标准平皿 Ames 试验中无或有 S9 条件下所有菌株结果均为阴性。此外，无或有 S9 时，组氨酸浓度在 0.5 mg/mL 及以上时菌株菌落数减少且使背景菌苔增厚。

结论  与标准平皿 Ames 试验相比，mini-Ames 试验易于出现阳性结果。组氨酸浓度范围在 0.2 ~ 0.3 mg/mL 时可影响细菌回复突变试验背景值，且高浓度组氨酸对菌株存在明显细菌毒性。因此有必要测定受试物中组氨酸含量或增加适宜的对照组，保证研究结果准确性。

Nitric oxide (NO) is a key gaseous signaling molecule involved in various human diseases, and real-time monitoring of its levels is crucial for understanding disease mechanisms. Fluorescent probes have become invaluable tools for detecting NO due to their high sensitivity, selectivity, temporal-spatial resolution, non-invasive nature, and convenience of operation. However, there are still many challenges in developing fluorescent probes that can be used for real-time quantification of NO with high selectivity, high sensitivity, low fluorescence background, and minimal cytotoxicity. This review provides a comprehensive overview of research progress of NO-responsive fluorescent probes in the past five years, classifying them by disease type, focusing on design strategies, NO response mechanisms, biological imaging applications, and real-time disease surveillance.

Objective  An inductively coupled plasma mass spectrometry (ICP-MS) method was developed for calculating the content of tetrofosmin and stannous chloride by simultaneously determining P and Sn content in tetrofosmin and stannous chloride for injection.

Methods  The elementals were determined by ICP-MS using simple pre-treatment processes such as 2% nitric acid dissolution and ultrasonic centrifugation. The acquisition mode of ICP-MS was selected as kinetic energy discrimination (KED) mode, and vanadium was used as internal standard for phosphorus determination, and antimony was used as internal standard for Sn determination, and the sampling was repeated three times to take the average value.

Results  Methodological verification indicated that the calibration curves showed good linearity between the concentrations of 0 ~ 10 μg/mL and their corresponding counting values for both P and Sn, with the correlation coefficients (r) of 1.000 and 0.9999, respectively. The limits of quantitation and detection of P were 3.073 × 10^-2 μg/mL and 1.014 × 10^-2 μg/mL, respectively. The limits of quantitation and detection of Sn were 9.850 × 10^-4 μg/mL and 3.251 × 10^-4 μg/mL, respectively. The recoveries of P and Sn were 101.0% and 100.3%, respectively, and the RSD were 5.35% (n = 9) and 4.68% (n = 9), respectively.

Conclusions  The ICP-MS method is simple and rapid. It can better meet the requirements for the determination of stannous chloride and the tetrofosmin in tetrofosmin and stannous chloride for injection.

干细胞供者知情同意书作为保护供者权益、确保干细胞研究和应用符合伦理规范的重要程序，理应受到研发和医疗机构的重视。2022 年中国医药生物技术协会颁布了《干细胞供者知情同意规范》团体标准，本文以该标准为主要依据，对国内相关机构向协会提供的 75 份干细胞供者知情同意书进行了分析。明确了标准发布前知情同意书在背景介绍、目的与用途、采集方法与采集后处置、风险防范、受益与隐私保护、费用和补（赔）偿等环节存在的问题。建议加强团体标准的培训和宣贯，完善干细胞供者知情同意，推动我国干细胞事业高水平规范化发展。

Objective  Streptomyces thermotolerans is a producer of Carbomycin, which is commonly utilized in the industry for biotransforming Tylosin into acetylisovaleryltylosin. However, the whole genome sequence information of this strain has not been reported. Herein, the whole genome of S. thermotolerans ATCC 11416 was sequenced and analyzed by bioinformatics software to predict the putative biosynthetic gene cluster (BGC) of secondary metabolites, as well as comparative genomics research.

Methods  The mycelium of S. thermotolerans ATCC 11416 was cropped, the qualified genomic DNA was extracted, and the whole genome of S. thermotolerans ATCC 11416 was sequenced using sequencing platform Illumina combined with PacBio. The resultant genomic sequence was analyzed by anti-SMASH software to find the BGC of secondary metabolites and the deduced compounds produced by these BGC, and the transcription level of these BGC was identified by qPCR. The whole genome of ATCC 11416 comparisons with other streptomyces were analyzed by TBtools software.

Results  The genome of S. thermotolerans ATCC 11416 consisted of a linear chromosome with a genome size of 8 279 432 bp and was presumed to contain 7356 genes with a GC content of 71.65%. It contained 66 tRNA and 18 rRNA sequences, and multiple repeats sequences had been identified. The BGCs of 26 secondary metabolites were identified from the genome, of which Cluster 8 was responsible for carbomycin biosynthesis. Using qPCR detection and comparison with key genes in Cluster 8, it was found that the functional genes in Clusters 1, 7, 13, 14, 15, 19 and 21 exhibited higher expression activity, while those in Clusters 5, 6, 9, 11, 12, 16, 18 and 24 showed lower expression activity. The functional genes in Clusters 2, 3, 4, 10, 17, 20, 22, 23 and 25 were almost not expressed, indicating putative silencing gene clusters. Among the silent gene clusters, Clusters 4, 10, 17, 20, 23, and 26 were low homologous with the known gene clusters and might be responsible for synthesizing new compounds. Genomic comparative analysis showed that S. thermotolerans ATCC 11416 and S. ambofaciens ATCC 23877 exhibited higher homology, and both produced 16-membered macrolide antibiotics. Genomic rearrangement phenomena such as multiple flips and translocations were found in genomic comparison.

Conclusion  The thermotolerant actinomycete Streptomyces thermotolerans ATCC 11416 harbors a medium-sized genome containing 26 BGCs, including a number of silent gene clusters with low homology. This lays the foundation for the subsequent activation of these silent gene clusters through molecular biological approaches to obtain new compounds.