To explore the inhibitory effect of ginkgolide B (GB) on MH7A human fibroblast-like synoviocytes (FLS) and its potential mechanism. Firstly, 20 μg/L tumor necrosis factor-α (TNF-α) was pretreated with MH7A to establish a cell model of arthritis. After incubation of MH7A cells with various concentrations of GB, CCK-8 assay, Transwell assay, and flow cytometry (FCM) were separately used to detect cell viability, cell invasion, and cell apoptosis rate and cell cycle; Real-time quantitative PCR and Western blot assay were performed to detect the apoptosis- and cycle-related gene transcriptions and protein expressions, respectively. The results showed that compared with the control group, GB dose- and time-dependently suppressed cell viability to a greater extent; GB significantly reduced cell invasive ability and increased cell apoptosis rate and proportion of G0/G1 phase in MH7A cells, along with increased transcription levels of Bcl-2-associated X protein (Bax) and p21 mRNA and decreased transcription levels of Bcl-2, myeloid cell leukemia 1(Mcl-1), protein kinase B (PKB; AKT), IP3K, Cyclin D1 and cyclin-dependent kinase 4 (CDK4) mRNA; GB remarkably increased expression levels of Bax, p21, and cleaved-Caspase 3 protein and decreased expression levels of Bcl-2, Mcl-1, p-AKT, p-PI3K, Cyclin D1, and CDK4 protein, with decreased ratios of p-PI3K/PI3K, p-AKT/AKT, and Bcl-2/Bax. In conclusion, GB blocks the G1-to-S cell cycle transition, suppresses cell viability and cell invasion and induces cell apoptosis of MH7A human RA-FLS via suppressing the PI3K/AKT signaling pathway.

Cationic carriers have demonstrated broad application prospects in drug delivery due to their excellent drug-loading capacity and delivery performance. However, their high-density positive surface charge often leads to systemic toxicity and nonspecific uptake, posing significant barriers to clinical translation. In recent years, the emergence of charge shielding and stimuli-responsive strategies has provided effective avenues for modulating biocompatibility and targeting specificity. This review systematically summarizes the applications of chemical modification, natural polymer coating, and biomimetic membrane strategies in charge shielding. Furthermore, it explores the roles of endogenous stimuli such as pH, enzymes, and reactive oxygen species, as well as exogenous triggers like light and ultrasound, in achieving precise activation and controlled release. With the integration of multi-functional modules and the development of intelligent delivery platforms, cationic carriers are progressively advancing from laboratory research toward clinical translation. This review also discusses the translational potential and critical technical bottlenecks of related delivery systems, aiming to provide a theoretical framework and some reference for the design of next-generation smart delivery systems.

Over the past few decades, tumor immunotherapy has revolutionized the landscape of cancer clinical treatment. There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immunotherapy. However, instead of a straightforward combination of multiple therapeutics, it is more preferable to pursue a synergistic effect by designing rational combinations as well as administration strategies, which are based on a comprehensive understanding of the physiological and pathological features. In this case, the timing and spatial distribution of the combination drugs become essential factors in achieving improved therapeutic outcomes. Therefore, the concept of Sequential Drug Delivery System (SDDS) is proposed to define the spatiotemporally programmed drug delivery/release through triggers of internal conditions and/or external interventions, thus complying with the dynamic disease evolution and the human immunity. This review summarizes the recent advancements in biomaterial-based SDDSs used for spatiotemporally-tuned combination tumor immunotherapy. Furthermore, the rationales behind various engineering strategies are discussed. Finally, an overview of potential synergistic mechanisms as well as their prospects for combination immunotherapy is presented.

OBJECTIVES: To explore the relationship between the Observer's Assessment of Alertness/Sedation (OAAS) score and the bispectral index (BIS) during propofol titration for general anesthesia induction and analyze the impact of BIS monitoring delay on anesthetic depth assessment. METHODS: This study was conducted among 90 patients (ASA class I-II) undergoing elective surgery under general anesthesia. For anesthesia induction, the patients received propofol titration at the rate of 0.5 mg·kg^-1·min^-1 till OAAS scores of 4, 3, 2, and 1 were reached. After achieving an OAAS score of 1, remifentanil (2 μg·kg⁻¹) and rocuronium (0.6 mg·kg⁻¹) were administered, and tracheal intubation was performed 2 min later. BIS values, mean arterial pressure (MAP), heart rate (HR), and propofol dosage at each OAAS score were recorded, and the correlation between OAAS scores and BIS values was analyzed. The diagnostic performance of BIS values for determining when the OAAS score reaches 1 was analyzed using ROC curve. RESULTS: All the patients successfully completed tracheal intubation. BIS values of the patients at each of the OAAS scores differed significantly (P<0.01), and the mean BIS value decreased by 4.08, 8.32, 5.43 and 5.24 as the OAAS score decreased from 5 to 4, from 4 to 3, from 3 to 2, and from 2 to 1, respectively. There was a significant correlation between the OAAS score and BIS values (ρ=0.775, P<0.001). The median BIS value for an OAAS score of 1 was 76, at which point 83.33% of the patients had BIS values exceeding 60. ROC curve analysis showed that for determining an OAAS score of 1, BIS value, at the optimal cutoff value of 84, had a sensitivity of 88.9%, a specificity of 73.3%, and an area under the curve of 0.842 (0.803-0.881). CONCLUSIONS OAAS score during induction of general anesthesia is strongly correlated with BIS value and is a highly sensitive and timely indicator to compensate for the delay in BIS monitoring.
Humans ; Propofol/administration & dosage* ; Male ; Female ; Middle Aged ; Anesthesia, General/methods* ; Adult ; Consciousness Monitors ; Aged ; Young Adult ; Monitoring, Intraoperative/methods* ; Electroencephalography

To better promote the development of film-coated formulations and membrane agents, the present study was carried out to investigate the critical material attributes (CMAs) of different sources and models of HPMC in terms of film-coating performance and the correlation between each of the CMAs and the film-coating-related properties, using 2910 HPMC as the research target. Firstly, various analytical techniques were used to characterize the CMAs and film coating-related properties of HPMC. Secondly, the CMAs and film coating-related properties of HPMC were systematically evaluated by principal component analysis (PCA) and orthogonal partial least-squares discrimination analysis (OPLS-DA). The CMAs and film-coating-related properties of HPMC were systematically evaluated to elucidate the intrinsic relationship between the CMAs and film-coating-related properties of HPMC. The results showed that there were significant differences in viscosity, weight-average molecular weight, film tensile strength, elongation, elastic modulus, dissolution time, and flexibility of HPMCs from different manufacturers. The results of PCA and OPLS-DA analyses indicated that these 11 variables showed some correlations with each other. Both mathematical models showed better differentiation and classification of HPMC samples, and the OPLS-DA model had a better classification effect than the PCA model. Therefore, in this study, the physicochemical properties and the film-forming characteristic of HPMC were comprehensively evaluated, and the correlation between them was further established using PCA and OPLS-DA. The impact degree of different CMAs on the film coating performance of HPMC was clarified, which can be used as an important reference for the selection of excipient quality control programs in excipient production and formulation research and development.

Objective:To develop and validate gas chromatographic methods for the determination of residual benzene in carbomer copolymer,carbomer homopolymer and carbomer interpolymer,to address the issues of the current method in the Chinese Pharmacopoeia in the actual detection process,such as low sensitivity and poor repeatability of benzene detection in the mixed reference solution,and to optimize and improve the current stand-ards for series of carbomer pharmaceutical excipients.Methods:Samples were separated on a column DB-624(30 m ×0.530 mm,3.00 μm)with temperature programming,the inlet temperature of 140 ℃,the detector tem-perature of 250 ℃,and the split ratio of 5∶1.The external standard method was adopted for the quantitative deter-mination of residual benzene.Results:The linearity was great across the range of 0.04-1.00 μg·mL-1(r=0.996 8),the injection precision of benzene was 6.8％(n=6),and the average recovery rate was 96.89％(RSD=8.1％,n=9).Conclusion:The gas chromatographic method established in this research is more specif-ic,with higher accuracy and precision compared to the current method in the Chinese Pharmacopoeia.This optimized method is more suitable for the determination of residual benzene content in carbomer copolymer,car-bomer homopolymer and carbomer interpolymer,providing reference and guidance for the quality management and the control of carbomer.

Objective:A gas chromatography analysis system for fatty acid compositions of hydrogenated palm glycerides was established to provide a reference for quality standards of hydrogenated palm glycerides.Methods:In this test,a DB-WAX(30 m ×0.53 mm,1.0 μm)strong polarity gas chromatographic column was employed with an injection volume of 1 μL and a split ratio of 120∶1.The initial column temperature was 70℃,sustained for 2 min,ramped up to 230 ℃ at a rate of 5 ℃ per minute,and maintained for 10 min,with the inlet temperature of 250 ℃ and the detector temperature of 250 ℃.Results:In this experiment,the gas chromatograph-ic method was established successfully to determine fatty acid compositions of hydrogenated palm glycerides.The validated results indicated that the method exhibited well-suited system applicability,specificity and precision,and the RSD(％)fulfilled the requirements.The limit of detection(LOD)and limit of quantification(LOQ)values of nine fatty acid methyl esters were defined,and fatty acid compositions of seven batches of samples were checked successfully.Conclusion:The GC methodology developed in this study is suitable for the analysis and determina-tion of fatty acid compositions in hydrogenated palm glycerides,which can serve as a reference for the quality control of this pharmaceutical excipient and the establishment of quality standards.

Pharmaceutical excipients of animal origin, an important part in pharmaceutical excipients, are widely used in pharmaceutical preparations.However, compared with the pharmaceutical excipients of other origins, pharmaceutical excipients of animal origin have more special requirements in many aspects, such as raw materials, production, quality control, storage, supervision, etc.Chinese Pharmacopoeia 2020 first included the Guideline for Pharmaceutical Excipients of Animal Origin, which introduces the basic ideas and technical requirements for the life cycle quality control of pharmaceutical excipients of animal origin based on the risk management concept.This article illustrates the specificity of the pharmaceutical excipients of animal origin, and interprets the main contents of this guideline in conjunction with relevant domestic and foreign regulations and technical documents, thereby providing comprehensive reference for the implementation of the guideline.

Taking plastic packaging materials as an example, this paper mainly summarizes the general principles of pharmacopoeias and guiding principles of relevant government departments related to the compatibility studies of drugs and packaging materials at home and abroad, with much reference to relevant monographs and literature. The purpose and specific methods of extraction and interaction studies are summarized and discussed. The existing problems and solutions in compatibility research are also proposed in this review to provide some refe-rence for researchers in relevant fields.

As one of the most important biological drugs, protein and peptide drugs have been increasingly used in the prevention, diagnosis and treatment of diseases in recent years. However, most of them need to be injected and lack of long-acting formulations, which brings many troubles to patients suffering from chronic diseases. In this review, we summarized the strategies for engineering long-acting formulations for proteins and peptides via preparation means, including extended-release injection, implant, oral preparations and transdermal drug delivery systems, and analyzed their release mechanisms, research advances, advantages and shortcomings, thereby providing potential approaches for promoting the formulation improvement of these drugs.