OBJECTIVE To investigate adverse event signals associated with ofatumumab and rituximab in the treatment of multiple sclerosis(MS), provide more evidences for the clinical safe medication based on the U.S. food and drug administration's adverse event reporting system(FAERS) data. METHODS Postmarking adverse event reports of ofatumumab and rituximab were extracted to form an analysis dataset. Disproportionality analysis combined with bayesian confidence propagation neural nework (BCPNN) was conducted for adverse event signal monitoring. Adverse events meeting threshold conditions were selected and summarized for analysis. RESULTS The ofatumumab group collected a total of 72 310 adverse event reports, of which 325 showed positive signals, covering 24 system organ classes (SOCs), involving “infections and infestations” “nervous system disorders” and “musculoskeletal and connective tissue disorders”. The rituximab group collected 23 203 adverse event reports, with 311 showing positive signals, covering 25 SOC, involving “injury, poisoning and procedural complications” “infections and infestations” and “nervous system disorders”. Except for “gastrointestinal disorders” and “eye disorders”, both drugs exhibited significant differences in each SOC. CONCLUSION There are substantial differences in the risk of adverse events between ofatumumab and rituximab in the treatment of MS. Therefore, medication monitoring is required during the treatment. Due to the limitations of real-world studies for quantitative analysis, the above conclusions need to be validated through large-scale cohort studies.

OBJECTIVE To prepare tetrahydropalmatine gel emulsion with Bletilla striata polysaccharide, and investigate its stability and dissolution characteristics in vitro. METHODS The nascent soap method combined with high pressure homogenization method were used to prepare tetrahydropalmatine gel emulsion. Using the particle size and polydispersity index (PDI) as evaluation indexes, the single factor response surface method was used to screen the optimal prescription, and the biological properties of tetrahydropalmatine gel emulsion were investigated. RESULTS The optimum formula was m(Bletilla striata polysaccharide)-m(konjac gum)=50∶1, triethanolamine mass fraction of 0.8%, stearic acid mass fraction of 2.0%. The gel emulsion of tetrahydropalmatine was milky white, fine, uniform and glossy, and had good moisturizing, coating and stability properties. The average particle size and PDI value were about (1.56±0.04) μm, (0.434±0.03), and the cumulative transmittance of the gel emulsion for 24 h was (915.23±85.55) μg·cm^-2. CONCLUSION The tetrahydropalmatine gel emulsion prepared in this experiment has good appearance, moisture retention, coating and stability, and good transdermal absorption rate. The research results can provide reference for the further development and utilization of tetrahydropalmatine.

OBJECTIVE To discuss the rationality of the current methods for examining viable bacterial count and contaminating bacteria in the standard of Bacillus cereus tablets, and optimize the two methods. METHODS The factors that affect the method for viable bacterial count were compared and analyzed, such as medium, diluent, dilution ratio, and pre-treatment, then the optimal experimental conditions were selected. The microbial limit test in the current standard was replaced with the contaminating bacteria test under the general chapter for probiotic in Chinese Pharmacopoeia part III, and its suitability was studied. RESULTS The optimized method for determination of viable bacterial count could more effectively recover Bacillus cereus in the sample, and the results were significantly higher than the current standard method. The use of a new method for detecting non-pathogenic bacteria can discover potential risks in the sample, and its suitability investigation results basically met the requirements of the Chinese Pharmacopoeia. CONCLUSION The new methods are suitable for the determination of viable bacterial count and detection of contaminating bacteria in Bacillus cereus tablets. The current standards for the determination of viable bacterial count and microbial limit testing cannot effectively monitor product quality risks. It is recommended to revise the methods. This can not only more effectively regulate products, but also better assist manufacturers in improving product quality.

OBJECTIVE To systematically study the micro-characteristics and microscopic characteristics of 9 commercially available Epimedium leaves, summarize more exclusive and practical features and provide reference for effective identification of Epimedii Folium on market. METHODS Using the character identification, micro-character identification, microscopic identification and combining with the technique of depth synthesis, high definition feature images of 9 species of Epimedium leaves were obtained. Some of the feature maps were extracted digitally and analyzed by SPSS 26.0 software. RESULTS The micro-characteristics of petiole hair, leaf margin spines, nipple and hairs on lower surface, parenchyma number on the base of leaf main vein transverse section, cuticle on the surface of leaf, as well as the microscopical characters of upper epidermal cell wave depth, non-glandular hair and nipple surface morphology, all of that can be regarded as specific features of 9 species of Epimedium leaves in classification and identification. There was statistically significant difference in the angle of thorns at the edge of leaves, the proportion of wave depth in upper epidermal cells and the density of nipple among all samples (P<0.05). CONCLUSION Nine kinds of Epimedium leaves could be distinguished through the micro-characteristics and micro-identification methods. The quantitative analysis and statistical analysis of micro-property will make up for the deficiency of traditional experience identification by subjective factors. The results of this study will provide a reference for the circulation, inspection, clinical medication and standard drafting and so on.

OBJECTIVE To ensure the scientificalness and rationality of proficiency testing and measurement audit projects in the field of authenticity identification of Chinese material medica and decoction pieces, and to provide new ideas for high quality development in this field. METHODS The key technical points were analyzed in the proficiency testing and measurement audit projects of authenticity identification of Chinese material medica and decoction pieces. RESULTS Proficiency testing and measurement audit projects of authenticity identification of Chinese material medica and decoction pieces are insufficient, which cannot meet the needs of market supervision. CONCLUSION Proficiency testing providers should seriously summarize and think about the key technical points in the proficiency testing and measurement audit projects of authenticity identification of Chinese material medica and decoction pieces. By improving capabilities and service, actively organizing proficiency testing projects, and establishing measurement audit sample bank, proficiency testing providers can constantly improve the quality of the proficiency testing and measurement audit projects in the field of authenticity identification of Chinese material medica and decoction pieces, and the shortcomings of external quality control in this field will be complemented which can promote the high quality development of traditional Chinese medicine(TCM) and TCM industry.

OBJECTIVE To research and evaluate risk of 18 polycyclic aromatic hydrocarbons(PAHs) in seed-fruit herbs based on a SPE-isotope dilution GC-MS/MS method for the determination of the residues. METHODS Using isotope as internal standard, the sample was extracted by n-hexane and purified by molecular imprinting solid phase extraction. GC-MS /MS method was used for the assay. The chromatographic column was DB-17ms(0.25 mm×30 m, 0.25 μm) with temperature programming and MRM detection. The preliminary risk assessment of polycyclic aromatic hydrocarbons (PAHs) in seeds and fruits of traditional Chinese medicine (TCM) was carried out by using toxicity equivalent factor method. RESULTS The calibration curves for the 18 kinds of typical PAHs were linear in the range of 2-50 ng·mL^-1. The average recovery rate was in the range of 77.25%-112.32%, with RSD 2.74%-15.89% (n=3). The LOQs were 0.2-1 μg·kg^-1 According to the risk assessment results, some varieties may have potential cancer risk. CONCLUSION This method is specific, sensitive, and can be used for residue detection of 18 typical kinds of PAHs in seed-fruit herbs. The residual amount of PAHs in some seeds and fruits of traditional Chinese medicine may have a potential cancer risk, which need attention.

OBJECTIVE To observe the inhibitory effect of ritonavir on human T-cell leukemia virus type-1 (HTLV-1) transmission and malignant proliferation of adult T-cell leukemia (ATL) cells, and explore its molecular mechanism. METHODS The proliferation and vitality of ritonavir on various leukemic cells were evaluated by CCK-8 and colony formation assay. The effects of ritonavir on HTLV-1 virus transmission were detected by flow cytometry, dual luciferase reporter gene technique, qPCR and Western blot. The effects of ritonavir on the cell cycle and apoptosis of ATL cells were examined through flow cytometry. RESULTS Ritonavir could inhibit the proliferation of four ATL cell lines and the clonal proliferation of HTLV-1 positive cell lines. The former exhibited a significant dose-effect relationship and had a more pronounced inhibitory effect on HTLV-1 positive cell lines (P<0.05). Additionally, the administration of ritonavir immediately after co-culture of HTLV-1 positive cell lines with JETWT35 cells resulted in a significant down-regulation of red fluorescent protein expression in JETWT35 and inhibited the transmission of HTLV-1 virus into recipient cells (P<0.01). Upon immediate addition of ritonavir to the co-culture system of HTLV-1 positive cell lines and Jurkat cells, there was a notable inhibition of HTLV-1-related gene Tax and other genes mRNA in recipient cells (P<0.01); however, no significant effect was observed when ritonavir was added 12 h after virus transmission. Morever, ritonavir demonstrated a does-dependent inhibition of gp46 expression on the cell membrane of the HTLV-1 positive cell line ATL-T, thereby suppressing the production of HTLV-1 virus (P<0.01). Ritonavir impeded cell progression into G₁ phase and facilitated apoptosis, with the apoptosis rate of HTLV-1 positive cell lines being significantly greater than that of HTLV-1 negative cell lines (P<0.05 or P<0.01). CONCLUSION Ritonavir exerts inhibitory effects on the production and transmission of HTLV-1 virus by diminishing the activity of WT-Luc virus promoter, suppressing the expression of HTLV-1-related virus genes (Tax, HBZ, Gag, Pol, and Env). Additionally, it inhibits the expression of the HTLV-1-positive membrane surface envelope protein subunit gp46. Futhermore, ritonavir induces apoptosis in ATL cells by arresting cell cycle in the G₁ phase, thereby effectively suppressing cell proliferation.

OBJECTIVE To provide suggestions for the compliance construction of complex formulation development processes, and promote the rationality and standardization of complex formulation development processes. METHODS Sorted out the characteristics and difficulties of the complex formulation development process, combined with the GMP technical requirements and verification focus, analyzed the common non-compliance situations in the complex formulation development process, and proposed compliance suggestions. RESULTS The development of complex formulations is often limited to excipients, instruments, pharmaceutical equipment, etc., with high requirements for personnel quality. Innovative production processes are often adopted or new technologies are introduced into conventional production processes, and the preparation process is complex with multiple quality control parameters, often requiring commissioned production or inspection. Some holders of complex formulations are emerging high-tech enterprises that lack experience in full lifecycle quality management. Enterprises often experience deficiencies in key personnel training, auxiliary material use and changes, equipment validation, process changes, technology transfer, deviation management, commissioned research, and data reliability. CONCLUSION Based on the characteristics of the complex formulation product development process and the key points of registration verification, the applicant needs to strengthen quality management, ensure the scientific, reasonable, and standardized development process of complex formulations, and ensure the safety and quality controllability of complex formulations.

OBJECTIVE To investigate the protective effect and possible mechanism of Chaihu Shugan Granules on acute liver injury in mice. METHODS Chaihu Shugan Granules was administered to mice at low, medium and high dosages (crude drug dose: 11.4, 22.8, 45.6 g·kg^-1) continuously for 7 d. Two hours after the last administration, the animal model was made with 0.2% tetrachloromethane (CCl₄) solution except the control group. The serum and liver tissues were collected after 12 h. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and superoxide dismutase (SOD), malondialdehyde (MDA), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and reactive oxygen species (ROS) in liver tissues were measured by ELISA. HE staining was conducted to reveal the histopathological changes in liver. Transcriptomics was used to obtain differentially expressed mRNA in liver tissues and enrich differentially expressed pathways, while metabolomics was used to obtain changes in liver endogenous metabolites and enriches pathways of differential metabolites using KEGG database. The expression and location of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38 MARK), kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in liver tissues were measured by immunohistochemistry and Western blot. RESULTS Compared with the model group, the serum levels of ALT, AST and MDA, IL-6, TNF-α and ROS in liver tissues of mice in each group of Chaihu Shugan Granules decreased significantly (P<0.05 or P<0.01), while the level of SOD in liver tissues increased significantly (P<0.01). The degree of necrosis and inflammatory infiltration in liver cells decreased significantly. Nqo1 gene and NAD(P)H: quinone oxidoreductase 1 (NQO1) expression were up-regulated while Ccl2 gene and monocyte chemotactic protein 1 (MCP-1) expression were down-regulated. Organic acids were significantly down-regulated and carbohydrate was significantly up-regulated, the expressions of JNK, p38 MARK and Keap1 in liver tissues were significantly decreased (P<0.05 or P<0.01), while the expressions of Nrf2 and HO-1 were significantly increased (P<0.01). CONCLUSION Chaihu Shugan Granules might have protective effect on CCl₄-induced acute liver injury in mice by activating the Keap1-Nrf2/HO-1 signal pathway.

OBJECTIVE To screen and study the effects of small activating RNA (saRNA) enhancing the expression of ABCG2 gene on renal and intestinal cell excretion of uric acid (UA) to explore a new type of therapeutic mechanism drugs to promote UA excretion. METHODS saRNAs targeting mice and human ABCG2 genes were designed and screened by real-time quantitative reverse transcription PCR(RT-qPCR) and Western blot in mice TCMK-1 and human HK-2 cells. The effect of the selected saRNA on the excretion of UA was examined in TCMK-1 and HK-2 cells. The mice saRNA was injected into the tail vein of hyperuricemia (HUA) model mice. The levels of serum uric acid (SUA), urinary uric acid (UUA), intestinal uric acid, blood urea nitrogen (BUN) and serum creatinine (SCr), and the activity of liver xanthine oxidase (XOD) in the mice were detected to verify the ability of selected saRNA to promote UA excretion. The pathological changes of kidney and small intestine were analyzed through H&E. The expression of ABCG2 in kidney and small intestine was analyzed by RT-qPCR, Western blot and immunohistochemistry. RESULTS Four saRNAs targeting ABCG2 were selected, 2 for mice and 2 for human, named saRNA-1/2 and hsaRNA-1/2 respectively, which increased the expression of ABCG2 in TCMK-1 and HK-2 cells (P<0.05), and promoted the extracellular excretion of UA (P<0.05). In HUA model mice, saRNA-1/2 increased the levels of UUA and intestinal UA (P<0.05), reduced the levels of SUA, BUN, and SCr (P<0.05), decreased the damage of HUA to kidney and small intestine, and enhanced the expression of ABCG2 in kidney and small intestine, but did not show significant effect on the activity of liver XOD (P>0.05). CONCLUSION The selected saRNAs could enhance the expression of ABCG2 and promote the excretion of UA in cells and mice, reducing SUA level.