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.

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.

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.

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  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.

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.

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 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  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.

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.

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.