Based on the implementation of GMP, comprehensive improvement of quality control measures, and consideration of the 3Rs principle for experimental animals, Several years ago, WHO, the European Pharmacopoeia and the FDA gradually abolished the testing for abnormal toxicity of biological products, and the Chinese Pharmacopoeia 2025 Edition(Volume Ⅲ)also revised the testing for abnormal toxicity of biological products. In order to help users of the Chinese Pharmacopoeia(Volume Ⅲ) better understand and implement this pharmacopoeia, this article provides a detailed review of the changes in regulatory concepts for abnormal toxicity test in various countries and the process of gradually phasing out abnormal toxicity test, as well as the actual situation of China’s pharmaceutical industry. It also interprets the ideas and considerations for revising the Chinese Pharmacopoeia 2025 Edition(Volume Ⅲ) on abnormal toxicity test for biological products.

Background As a pillar industry in China, the manufacturing sector has a high incidence of non-fatal occupational injuries. The factors influencing non-fatal occupational injuries in this industry are closely related at various levels, including individual, equipment, environment, and management, making the analysis of these influencing factors complex. Objective To identify influencing factors of non-fatal occupational injuries among manufacturing workers, providing a basis for targeted interventions and surveillance. Methods A total of 2243 frontline workers from cable and shipbuilding enterprises were selected as study subjects to investigate the incidence of non-fatal occupational injuries and collect information at four levels: individual, equipment, management, and environment in past 12 months. Data balancing was performed using resampling, and LASSO regression was used to select factors of non-fatal occupational injuries. The influence degree and type of variables were judged based on the magnitude of the estimated coefficients of each variable, where variables with estimated coefficients > 0 are risk factors, and those <0 are protective factors. The area under the receiver operating characteristic (ROC)curve (AUC) was used to test the performance of the model, with an AUC value > 0.7 indicating good model performance. Results Among the 2243 frontline workers, males accounted for 77.7% (1742 out of 2243), with the main age range being 40-49 years old, representing 29.5% (661 out of 2243), 82.7% of the workers (1854 out of 2243) were married, and 55.6% (1248 out of 2243) had a junior middle school education level. The average monthly income for 51.0% (1144 out of 2243) of the workers was between 5000 and 6999 Chinese Yuan. The incidence of non-fatal occupational injuries among the manufacturing workers was 8.4% (189/2243) in the past 12 months. Among the 22 factors associated with the occurrence of non-fatal occupational injuries (P<0.05), 10 were individual-level factors, including gender, smoking, alcohol consumption, colleague relationships, average exercise duration, job burnout, work fatigue, musculoskeletal disorders, cardiovascular diseases, and neurological and sensory organ diseases; 3 were equipment-level factors, including equipment operability, hazardous workpieces, and safety hazards; 5 were environmental-level factors, including low temperatures, special operations, noise, workspace size, and dirty and disorderly environment; and 4 were management-level factors, including daily working hours, weekly working days, overtime, and pre-job technical training. The AUC value of the LASSO regression model was 0.704 and the final model retained a total of 10 variables. Among them, there were 7 risk factors for non-fatal occupational injuries (coefficient > 0), including safety hazards, musculoskeletal disorders, dangerous workpieces, job burnout, dirty and disorderly environment, smoking, and male gender; and 3 protective factors (coefficient < 0), including pre-job technical training, good colleague relationship, and long working days per week. Conclusion Manufacturing enterprises need to focus on the incidence of non-fatal occupational injuries and conduct targeted interventions for non-fatal occupational injuries by controlling potential safety hazards, providing pre-job technical training, reducing dangerous workpieces, rectifying working environment, and reasonably arranging working hours.

Chimeric antigen receptor T (CAR-T) cells have reshaped the treatment landscape of hematological malignancies, offering a potentially curative option for patients. Despite these major milestones in the field of immuno-oncology, growing experience with CAR-T cells has also highlighted several limitations of this strategy. The production process of CAR-T cells is complex, time-consuming, and costly, thus leading to poor drug accessibility. The potential carcinogenic risk of viral transfection systems remains a matter of controversy. Treatment-related side effects, such as cytokine release syndrome, can be life-threatening. And the biggest challenge is the inadequate efficacy related to poor infiltration and retention of CAR-T cells in tumor tissues and impaired T cell activation caused by the immunosuppressive tumor microenvironment (TME). Innovative strategies are urgently needed to address these problems, and nanomedicine offers good solutions to these challenges. In this review, we provide a comprehensive summary of recent advancements in the application of nanomaterials to enhance CAR-T cell therapy. We examine the role of innovative nanoparticle-based delivery systems in the production of CAR-T cells, with a particular focus on polymeric delivery systems and lipid nanoparticles (LNPs). Furthermore, we explore various strategies for delivering immune stimulators, which significantly enhance the efficacy of CAR-T cells by modulating T cell viability and functionality or by reprogramming the immunosuppressive TME. In addition, we discuss several novel therapeutic approaches aimed at mitigating the adverse effects associated with CAR-T therapies. Finally, we offer an integrated perspective on the future challenges and opportunities facing CAR-T therapies.
Humans ; Nanomedicine/methods* ; Receptors, Chimeric Antigen/metabolism* ; Immunotherapy, Adoptive/methods* ; T-Lymphocytes/immunology* ; Nanoparticles/chemistry* ; Animals

Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, overshadowing its influence on the biological effects of formulations. In this study, we reevaluated the delivery effect of CH using widely applied lipid microspheres (LM) as a model DDS. We conducted comprehensive investigations into the impact of CH on the distribution, cell uptake, and protein corona (PC) of LM at sites of cardiovascular inflammatory injury. The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage. Then, the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy. Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in vascular endothelial cells and estrogen receptor alpha (ERα) protein levels in myocardial cells, thereby enhancing LM uptake at cardiovascular inflammation sites. Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V (Apoa5); this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites. It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations. The findings enhance the conceptualization of CH and LM delivery, providing novel strategies for investigating prescription factors' bioactivity.

Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular disease.Despite the current treatments,mortality and disability still remain high.Sonodynamic therapy(SDT),a non-invasive and localized methodology,has been developed as a promising new treatment for inhibiting atherosclerotic progression and sta-bilizing plaques.Promising progress has been made through cell and animal assays,as well as clinical trials.For example,the effect of SDT on apoptosis and autophagy of cells in AS,especially macrophages,and the concept of non-lethal SDT has also been proposed.In this review,we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS;we elaborate on SDTs therapeutic effects and mechanisms in terms of macrophages,T lymphocytes,neovascularization,smooth muscle cells,lipid,extracellular matrix and efferocytosis within plaques;additionally,we discuss the safety of SDT.A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.

Objective To explore the application value of an improved volume rendering algorithm based on Cuda in CT vascular imaging three-dimensional reconstruction.Methods Five cases of head and neck vascular computed tomography angiography(CTA)examinations and five cases of coronary CTA examinations were selected.The traditional Bounding-Box algorithm and the Cuda-based volume rendering reconstruction method were used for vascular three-dimensional reconstruction.The reconstruction speed and quality of the two algorithms were compared.Results Running the traditional algorithm on an RTX2060 graphics card took 50-60 ms per frame,while running the algorithm described in this study took 25-35 ms per frame,resulting in approximately a 1x speed improvement.On an RTX3060,the algorithm described in this study took 18-23 ms per frame,resulting in approximately a 1x speed improvement.The reconstruction results from all ten cases demonstrated that the algorithm described in this study provided clearer visualization of small blood vessels in the head and neck region and the distal coronary arteries.Conclusion The Cuda-based development framework achieves faster rendering speed and better image quality compared to the traditional Bounding-Box algorithm.

Objective:To construct an objective and scientific core competence training system for intensive care unit (ICU) specialized nurses in Yunnan Province, and to provide references for formulating a homogeneous and standardized ICU specialized nurse training strategy and assessment.Methods:Based on the theoretical basis of the nurse-patient safety competency framework, the relevant literature of nursing job competence was consulted, the core competency training system of ICU specialized nurses in Yunnan Province was constructed, and the expert letter questionnaire was designed through theoretical analysis. From January to May 2020, 15 experts of critical care medicine from Yunnan Province were consulted by Delphi method to establish a core competency training system for ICU specialized nurses in Yunnan Province. SPSS 21.0 was used to input and analyze the data.Results:A total of 2 rounds of Delphi expert consultation were carried out. The final core competency indicators for ICU specialized nurses included effective communication, teamwork, safety risk management, nursing quality improvement and professionalism, including 5 first-level indicators, 14 second-level indicators and 59 third-level indicators. The effective recovery rates of the two rounds of Delphi expert consultation questionnaires were 100.00% (15/15) and 86.67% (13/15), the expert authority coefficient values were 0.863 and 0.881 respectively, the Kendall harmony coefficients of the first-level index, the second-level index and the third-level index were 0.381, 0.299 and 0.250, and χ2 value was 22.86, 58.22 and 217.30, with statistically significant differences ( P<0.001). The 5 first-level indicators were safety risk management (0.360), professionalism (0.280), teamwork (0.200), nursing quality improvement (0.120), and effective communication (0.040) in descending order. Conclusions:The established core competence training system for ICU specialized nurses in Yunnan Province based on patient safety is reliable and scientific, which can provide objective basis for the on-the-job training, evaluation and development of patient safety education courses for ICU specialized nurses in Yunnan Province.

OBJECTIVE To identify and classify the chemical components and components absorbed into blood of Sishen Pills u-sing ultra-high performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry.METHODS SD rats were divided into blank group and drug administration group.The rats in drug administration group were given water extract of Sishen Pills formula intragastrically,and blank and drug-containing plasma were collected respectively.A Hypersil GOLD VANQUISH column(2.1 mm×100 mm,1.9 μm)was used,with 0.1%formic acid water acetonitrile as the mobile phase,gradient elution,volume flow rate of 0.3 mL·min-1,and column temperature of 35℃.Electrospray ion source(ESI)with positive and negative ion scanning mode was used for chromatographic separation and mass spectrometry data acquisition.The chemical components of Sishen Pills were identi-fied by comparing the exact molecular mass,fragment ion information and relative retention time with the map of reference substance,matching with the self-established database and combining with literature reports.On this basis,the components absorbed into blood of Sishen Pills were analyzed by comparing the blank plasma and drug-containing plasma.RESULTS A total of 181 chemical compo-nents were identified from Sishen Pills,mainly including flavonoids,alkaloids,lignans and other components.A total of 49 prototype blood components were identified from the plasma samples,mainly including flavonoids,alkaloids and other components.CONCLU-SION A variety of chemical components in Sishen Pills and drug-containing plasma are comprehensively,accurately and quickly i-dentified,and all of them are assigned to the various medicinal materials in the prescription.This study provides reference for the qual-ity control,basic research on medicinal effect materials and clinical application of Sishen Pills.

Objective:To analyze the risk factors of biliary infection after endoscopic retrograde cholangiopancreatography (ERCP) in patients with malignant biliary obstruction.Methods:Clinical data of 160 patients with malignant biliary obstruction admitted to the Affiliated People's Hospital of Ningbo Univer-sity from June 2017 to June 2022 were retrospectively analyzed, including 89 males and 71 females, aged (65.1±8.0) (range, 41-78) years old. Patients were divided into two groups according to the occurrence of biliary infection within 30 days after ERCP: infected group ( n=30) and uninfected group ( n=130). Multivariate logistic regression was used to identify the risk factors of postoperative biliary infection. Results:The incidence of biliary infection after ERCP was 18.8% (30/160) in the patients with malignant biliary obstruction. A total of 43 strains of pathogenic bacteria were detected, including 34 Gram-negative strains and nine Gram-positive strains. The most common pathogenic bacterium was Escherichia coli. Multivariate analysis showed patients with diabetes mellitus ( OR=2.356, 95% CI: 1.587-5.441, P=0.001), sphincter dysfunction ( OR=2.651, 95% CI: 1.854-6.225, P=0.005), preoperative albumin <35 g/L ( OR=3.225, 95% CI: 2.041-5.689, P=0.002), preoperative hemoglobin <110 g/L ( OR=3.424, 95% CI: 2.115-6.333, P=0.003) suffered a higher risk of biliary infection after ERCP. Conclusion:Diabetes mellitus, sphincter dysfunction, lower levels of preoperative albumin and hemoglobin are independent risk factors for biliary infection after ERCP in patients with malignant biliary obstruction.