The Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines （hereinafter referred to as the Guidelines） is first specialized in the field of drug safety for oral Chinese patent medicines （OCPMs） in China. Rooted in China's healthcare context， the Guidelines address the unique usage patterns and risk characteristics of OCPMs， filling a regulatory gap in the pharmacovigilance framework specific to this category. To facilitate accurate understanding and effective implementation of the Guidelines， and to promote the standardized development of pharmacovigilance practices for OCPMs， this study offered a systematic interpretation based on its three core components. In the domain of risk monitoring and reporting， the paper analyzed the rationale for multi-source information integration and clarified the criteria for identifying key products and target populations for intensive monitoring. Regarding risk assessment， the Guidelines were examined from three dimensions of formulation components， medication behaviors， and population to address complex safety issues arising from medicinal constituents， irrational use， and individual susceptibility. In the area of risk control， the analysis focused on context-based interventions and dynamic closed-loop management strategies， exploring practical pathways to shift from passive response to proactive risk mitigation. Furthermore， this paper evaluated the applied value of the Guidelines and identified implementation challenges， such as insufficient capacity at the primary-care level and limited digital infrastructure. In response， the study proposed optimization strategies including establishing a dynamic updating mechanism， strengthening training at the grassroots level， and incorporating artificial intelligence to enhance pharmacovigilance capacity. This interpretation aims to provide actionable insights for marketing authorization holders （including manufacturers）， pharmaceutical distributors， healthcare institutions， and research organizations， ultimately supporting the establishment and refinement of a full lifecycle pharmacovigilance system for OCPMs.

[摘 要] 目的：探讨烯醇化酶1（ENO1）对胃癌细胞增殖、迁移及侵袭的影响及其分子机制。方法：通过WB法检测ENO1在人胃癌细胞HGC27、MKN-45、N-87、MGC803、BGC-823及人胃黏膜上皮细胞GES-1中的表达水平，利用CRISPR、过表达等基因编辑工具分别构建ENO1敲低及敲低—恢复表达细胞株，将MKN-45和BGC-823细胞分别分组为Ctrl组、ENO1 KD组、ENO1 KD-OE组。通过克隆形成实验、EdU染色、划痕实验、Transwell实验、流式细胞术检测敲低或敲低—恢复表达ENO1对胃癌细胞增殖、迁移、侵袭及凋亡的影响。构建胃癌细胞裸鼠移植瘤模型，通过小动物活体成像技术及肿瘤组织块测量观察ENO1对肿瘤生长的影响。在MKN-45细胞中通过RNA干扰技术沉默ENO1，利用RNA免疫共沉淀-转录组测序（RIP-Seq）结合生物信息学分析技术鉴定ENO1下游的靶基因，分析ENO1调控胃癌细胞增殖、迁移及侵袭的分子机制。结果：ENO1在胃癌细胞中表达水平均显著升高（P < 0.01或P < 0.001）。在MKN-45和BGC-823细胞中敲低ENO1可显著降低胃癌细胞的增殖、迁移、侵袭能力并促进细胞凋亡（P < 0.001或P < 0.000 1）；回复实验结果显示，恢复ENO1的表达后，胃癌细胞的增殖、迁移、侵袭能力均显著提高并减少细胞凋亡（P < 0.05或P < 0.01或P < 0.001或P < 0.000 1）。裸鼠荷瘤实验结果表明，敲低ENO1的表达可以显著抑制裸鼠移植瘤的生长（P < 0.000 1）。与ENO1蛋白具有相互作用的差异基因主要富集于RNA剪切相关通路，且ENO1蛋白与PKM基因具有相互作用，胃癌组织中ENO1与PKM2基因表达事呈正相关（r = 0.886）。结论：ENO1在胃癌细胞中呈高表达，其通过与PKM的前体mRNA相互作用影响PKM的RNA剪接过程，进而调控PKM2的表达水平并促进胃癌的进展。

ObjectiveTo monitor the real-time changes in ammonia concentration in the laboratory animal facility environment before, during, and after the air conditioning system stops supplying air, so as to provide a basis and reference for developing emergency plans for the shutdown of the air conditioning system. MethodsThe laboratory animal facilities of the Wuhan Institute of Biological Products were used as the research object. Ammonia concentration detectors were used to monitor ammonia concentration continuously in the environment of conventional rabbit production facility, SPF hamster production facility, and SPF guinea pig experimental facility before and after the passive shutdown due to repairs and active maintenance shutdown of the air conditioning system, as well as the time for the ammonia concentration to return to daily levels after resuming air supply. ResultsUnder both shutdown modes of the air conditioning system, the trend of ammonia concentration changes in different laboratory animal facilities was consistent, showing a rapid increase after shutdown and a rapid decrease after resuming air supply. Under active maintenance shutdown, the maximum ammonia concentrations in the conventional rabbit production facilities, SPF hamster production facilities, and SPF guinea pig experimental facilities were 9.81 mg/m³, 14.27 mg/m³, and 6.98 mg/m³, respectively. Within 12 minutes after resuming air supply, ammonia concentration could return to normal daily levels. Under passive long-term shutdown, ammonia concentration value was positively correlated with the duration of air supply suspension. As the shutdown duration increased, ammonia concentration continued to increase. The maximum ammonia concentration values in the three facilities occurred at 88 minutes (38.06 mg/m³), 40 minutes (18.43 mg/m³), and 34 minutes (15.61 mg/m³) after air supply suspension, respectively.Within 11 minutes after resuming air supply, ammonia concentration could return to normal daily levels. ConclusionShutdown of the air conditioning system causes a rapid increase in ammonia concentration in laboratory animal facilities, and the rise in ammonia concentration is positively correlated with the duration of air supply suspension. Therefore, when an emergency shutdown of the air-conditioning system is required due to maintenance or other reasons, backup fans should be provided in accordance with the requirements of GB 50447-2008 "Architectural and Technical Code for Laboratory Animal Facilities". Older facilities should make adequate preparations and develop a scientifically sound emergency plan.

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Bufalin(BF)has a significant anti-tumor effect, but its clinical application is severely restricted by its high toxicity and poor water solubility. In this study, Scrophularia ningpoensis polysaccharide(SNP)and ursodeoxycholic acid(UDCA) were synthesized into an SNP-UDCA conjugate. BF was encapsulated to prepare BF/SNP-UDCA nanoparticles(NPs). The amphiphilic compound SNP-UDCA was synthesized via the one-step method, and its structure was characterized by Fourier-transform infrared spectroscopy(FT-IR)and proton nuclear magnetic resonance(~1H-NMR). The preparation process of BF/SNP-UDCA NPs was optimized through single-factor investigations. The encapsulation efficiency and drug-loading capacity of BF/SNP-UDCA NPs were determined by high-performance liquid chromatography(HPLC). The molecular form of BF/SNP-UDCA NPs was characterized by using a transmission electron microscope, X-ray diffraction(XRD), and differential scanning calorimeter(DSC). Additionally, the stability of BF/SNP-UDCA NPs was evaluated. The release behavior of BF/SNP-UDCA NPs at different pH values was determined by dialysis. The in vitro anti-tumor effect of BF/SNP-UDCA NPs was evaluated by MTT cytotoxicity assay, flow cytometry for apoptosis, and cellular uptake. The in vitro liver targeting was evaluated by measuring cellular uptake by laser confocal microscopy. The results demonstrated that the SNP-UDCA conjugate was successfully synthesized through an esterification reaction between SNP and UDCA. The preparation process of BF/SNP-UDCA NPs was as follows: the feed ratio of SNP-UDCA to BF was 2∶1, the ultrasonic time was 30 minutes, and the stirring time was two hours. The prepared BF/SNP-UDCA NPs were spherical in shape, with a particle size of(252.74±6.05)nm, an encapsulation efficiency of 65.00%±2.51%, and a drug-loading capacity of 6.80%±0.44%. The XRD and DSC results indicated that BF was encapsulated within the NPs and existed in a molecular or amorphous state. The short-term stability of BF/SNP-UDCA NPs and stability in DMEM medium are good, and their in vitro release behavior followed the first-order equation and was pH-dependent according to the in vitro experiment. Compared with BF, BF/SNP-UDCA NPs at the same concentration showed significantly stronger cytotoxicity and apoptotic effects on HepG2 cells(P<0.05, P<0.01). The uptake of coumarin 6(C6)/SNP-UDCA NPs in HepG2 cells was time-dependent and higher than that in HeLa cells at the same concentration of C6/SNP-UDCA NPs. Moreover, after treatment with SNP, the uptake of C6/SNP-UDCA NPs in HepG2 cells decreased. In conclusion, the preparation process of BF/SNP-UDCA NPs was simple and feasible. BF/SNP-UDCA NPs could enhance the targeting ability and inhibitory effect of BF on liver cancer cells. This study will provide a foundation for liver-targeting nanoformulations of BF.
Bufanolides/pharmacology* ; Nanoparticles/chemistry* ; Humans ; Drug Carriers/chemistry* ; Ursodeoxycholic Acid/chemistry* ; Antineoplastic Agents/pharmacology* ; Polysaccharides/chemistry* ; Scrophularia/chemistry* ; Liver Neoplasms/physiopathology* ; Hep G2 Cells

This study aims to explore the specific mechanism by which puerarin inhibits ferroptosis and improves the myocardial contractile function in myocardial hypertrophy through the nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE)/heme oxygenase-1(HO-1) signaling pathway. The hypertrophic cardiomyocyte model was established using phenylephrine, and H9c2 cells were divided into control group, model group, puerarin group, and puerarin+ML385 group. Cell viability and surface area were detected by cell counting kit-8(CCK-8) and immunofluorescence experiments. The mitochondrial membrane potential and Ca~(2+) concentration were measured. The ferroptosis-related indicators were detected by biochemical and fluorescence staining methods. The expression of proteins related to ferroptosis and the Nrf2/ARE/HO-1 signaling pathway was detected by Western blot. A myocardial hypertrophy model was established, and 40 rats were randomly divided into sham group, model group, puerarin group, and puerarin+Nrf2 inhibitor(ML385) group, with 10 rats in each group. Echocardiogram, hemodynamic parameters, and myocardial hypertrophy parameters were measured. Histopathological changes of myocardial tissues were observed by hematoxylin and eosin(HE) staining and Masson staining. Biochemical methods, enzyme-linked immunosorbent assay(ELISA), and fluorescence staining were used to detect inflammatory factors and ferroptosis-related indicators. Immunohistochemistry was used to detect the expression of proteins related to ferroptosis and the Nrf2/ARE/HO-1 signaling pathway. Cell experiments showed that puerarin intervention significantly enhanced the viability of hypertrophic cardiomyocytes, reduced their surface area, and restored mitochondrial membrane potential and Ca~(2+) homeostasis. Mechanism studies revealed that puerarin promoted Nrf2 nuclear translocation, upregulated the expression of HO-1, solute carrier family 7 member 11(SLC7A11), and glutathione peroxidase 4(GPX4), and decreased malondialdehyde(MDA), reactive oxygen species(ROS), and iron levels. These protective effects were reversed by ML385. In animal experiments, puerarin improved cardiac function in rats with myocardial hypertrophy, alleviated myocardial hypertrophy and fibrosis, inhibited inflammatory responses and ferroptosis, and promoted nuclear Nrf2 translocation and HO-1 expression. However, combined intervention with ML385 led to deterioration of hemodynamics and a rebound in ferroptosis marker levels. In conclusion, puerarin may inhibit cardiomyocyte ferroptosis through the Nrf2/ARE/HO-1 signaling pathway, thereby improving myocardial contractile function in myocardial hypertrophy.
Animals ; NF-E2-Related Factor 2/genetics* ; Rats ; Ferroptosis/drug effects* ; Signal Transduction/drug effects* ; Isoflavones/pharmacology* ; Male ; Rats, Sprague-Dawley ; Cardiomegaly/genetics* ; Myocytes, Cardiac/metabolism* ; Antioxidant Response Elements/drug effects* ; Myocardial Contraction/drug effects* ; Heme Oxygenase-1/genetics* ; Cell Line

ObjectiveTo analyze the evolutionary characteristics and genetic variations of the HA (hemagglutinin) and NA (neuraminidase) genes of influenza A(H1N1) viruses in Shanghai during 2024, to investigate their transmission patterns, and to evaluate their potential impact on vaccine effectiveness. MethodsFrom January to October 2024, throat swab specimens were collected from influenza like illness (ILI) patients at 4 hospitals in Shanghai. Real-time fluorescence ploymerase chain reaction (RT-PCR) was used for virus detection and isolation of H1N1 influenza viruses. Forty influenza A(H1N1) virus strains were sequenced using Illumina NovaSeq 6000 platform, followed by phylogenetic analyses, genetic distance analysis, and amino acid variation analyses of HA and NA genes. ResultsPhylogenetic tree of the HA and NA genes revealed that the 40 influenza A(H1N1) virus strains circulating in Shanghai in 2024 exhibited no significant geographic clustering, with a broad origin of strains and complex transmission chains. Genetic distance analyses demonstrated that the average intra-group genetic distances of HA and NA genes among the Shanghai strains were 0.005 1±0.000 6 and 0.004 6±0.000 6, respectively, which were comparable to or higher than those observed in global surveillance strains. Both HA and NA genes displayed frequent mutations. Compared to the 2023‒2024 and 2024‒2025 Northern Hemisphere A(H1N1) vaccine strains (WHO-recommended), the HA proteins of 40 Shanghai strains exhibited amino acid substitutions at positions 120, 137, 142, 169, 216, 223, 260, 277, 356 and 451, with critical mutations at positions 137 and 142 located within the Ca2 antigenic determinant. Furthermore, mutations in the NA protein were observed at positions 13, 50, 200, 257, 264, 339 and 382. ConclusionThe genetic background of the 2024 Shanghai influenza A(H1N1) virus strains is complex and diverse, and antigenic variation may affect vaccine effectiveness. Therefore, it is recommended to enhance genomic surveillance of influenza viruses, evaluate vaccine suitability, and implement more targeted prevention and control strategies against imported influenza viruses.

Objective:To investigate the important clinical features and prognosis of febrile infection-related epilepsy syndrome(FIRES).Methods:A retrospective analysis was performed for the data of 15 children with FIRES who were hospitalized and treated in Peking University First Hospital from March 2022 to June 2024,including clinical features,treatment regimens,and prognosis,and follow-up was performed by telephone.Results:The median duration of status epilepticus was 15 days for all children.Of all 15 children,14(93.3%)were comorbid with disturbance of consciousness,8(53.3%)were comorbid with respiratory failure and underwent endotra-cheal incubation,and 13(86.7%)had been admitted to the intensive care unit.In the acute stage,7 children underwent the examination of various inflammatory factors in blood and cerebrospinal fluid,including interleukin(IL)-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,and tumor necrosis factor-α,and all 7 children had significant increases in the levels of inflammatory factors in cerebrospinal fluid,which were significantly higher than the levels of inflammatory factors in serum.Of all 15 children,12(80%)had diffuse slow wave changes on electroencephalography,and migrating focal seizures were detected in 7 children(46.7%).Cranial magnetic resonance im-aging(MRI)manifestations in the acute stage included temporal and insular cortical edema(60%),abnormal white matter signal(33.3%),and claustrum sign(13.3%),and MRI features in the chronic stage included the deepening of cerebral sulci(75%)and ventricular dilatation(33.3%).The treatment in the acute stage in-cluded intravenous drip of gamma-globulin and high-dose methyl-prednisolone in 15 children(effective in 2 children),ketogenic diet in 4 children(effective in 1 child),tocilizumab in 5 children(effective in 3 children),and anakinra in 2 children(effective in 1 child).As of the last follow-up,the median duration of disease was 14.0 months(4-65 months)for all patients,and only 2 children achieved complete seizure control,while the remaining 13 children had refractory epilepsy.Cognitive impairment was observed in 93.3%of the children.Conclusion:FIRES often has acute and severe conditions,and first-line immunotherapies often have a poor therapeutic ef-fect.Tocilizumab and anakinra may be effective in some patients with seizures in the acute stage.

Objective To explore the effectiveness of a nutritional intervention in rescuers who screened positive for depression. Methods A randomized controlled trial design was employed.From June to August,2022,4,460 rescuers were screened using the Self-Rating Depression Scale(SDS),and 1,615 positive cases were identified.Thirty-one volunteers were recruited and randomly divided into a nutritional intervention group and a control group.The intervention group received health education and nutritional intervention(a compound paste therapy primarily composed of red roses and Seville orange flowers),while the control group received psychological education.SDS scores were assessed before and after the intervention. Results There was a statistically significant decline in SDS scores in the nutritional intervention group after the intervention(P<0.05).Furthermore,the SDS scores of the intervention group were significantly lower than those of the control group,both before and after the intervention(P<0.05).No severe adverse reactions were observed during safety evaluation. Conclusion The nutritional intervention effectively reduced the depression scores in rescuers.Early nutritional intervention is recommended for rescuers who initially screen positive for depression.

Objective To explore the value of energy spectrum CT based material imaging for quantitatively and qualitatively evaluating lumbar intervertebral disc degeneration.Methods Lumbar energy spectrum CT and MRI were collected from 82 patients with back and leg pain,and 74 keV CT,water(chondroitin sulfate[CS])and CS(water)material images were obtained.Intervertebral discs Pfirrmann grading(PG)was performed based on MRI.CT values,water(CS)and CS(water)concentration of nucleus pulposus(NP)and annulus fibrosus(AF)in lumbar intervertebral disc with different PG grades were compared,and the relations with PG grades were analyzed.Visual classification of lumbar intervertebral disc was performed based on water(CS)and CS(water)falsecolor map,while PG distribution of different visual classification were compared,and the relations with PG grades were observed.Results Totally 250 lumbar intervertebral discs were enrolled,including 22 of PG Ⅰ,49 of PG Ⅱ,83 of PG Ⅲ and 96 of PG Ⅳ.CT values,water(CS)and CS(water)concentration of anterior AF,NP and posterior AF of intervertebral disc with different PG grades were significantly different(all P＜0.001),and CT values were negatively correlated with PG grades(rs=-0.504,-0.399,-0.258,all P＜0.001),while water(CS)concentration was positively correlated(rs=0.476,0.753,0.324,all P＜0.001)but CS(water)concentration was negatively correlated with PG grades(rs=-0.486,-0.760,-0.329,all P＜0.001).Significant differences of PG grades were found among different water(CS)and CS(water)falsecolor images visual classification(all P＜0.001),while water(CS)and CS(water)falsecolor images visual classification were all positively correlated with PG grades(all rs≥0.700,all P＜0.001).Conclusion Energy spectrum CT based material imaging could be used for quantitatively and qualitatively evaluating lumbar intervertebral disc degeneration.