To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

Objective A new occipital bone removal technology was applied to improve the success rate of brain removal.Methods The skull was sawed based on the traditional brain removal technology,and part of the occipital bone was removed downward centered in external occipital protuberance to the foramen magnum,then exposed the telencephalon,cerebellum and posterior medulla oblongata.After that,removed the tentorium cerebelli and cut down the medulla oblongata and the related cranial nerves at the skull base,then removed the brain tissues.Results The removed brain tissues had structurally intact telencephalon,cerebellum and brain stem,clear vessels in the cerebral sulci,and relatively intact optic chiasm,olfactory tracts and vertebro-basilar arteries.Conclusion Brain removal through a fenestration on the external occipital protuberance can effectively preserve the integrity of brain specimens,and improve the success rate of brain removal,which is of great significance for central nervous system teaching and improvement of human brain tissue repositories.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

Objective A new occipital bone removal technology was applied to improve the success rate of brain removal.Methods The skull was sawed based on the traditional brain removal technology,and part of the occipital bone was removed downward centered in external occipital protuberance to the foramen magnum,then exposed the telencephalon,cerebellum and posterior medulla oblongata.After that,removed the tentorium cerebelli and cut down the medulla oblongata and the related cranial nerves at the skull base,then removed the brain tissues.Results The removed brain tissues had structurally intact telencephalon,cerebellum and brain stem,clear vessels in the cerebral sulci,and relatively intact optic chiasm,olfactory tracts and vertebro-basilar arteries.Conclusion Brain removal through a fenestration on the external occipital protuberance can effectively preserve the integrity of brain specimens,and improve the success rate of brain removal,which is of great significance for central nervous system teaching and improvement of human brain tissue repositories.

Objective:To evaluate the gene mutation profile and prognostic significance of adult cytogenetically normal acute myeloid leukemia (CN-AML) with CEBPA-bZIP mutation. Methods:Targeted sequencing was implemented on the diagnostic bone marrow DNA samples of 141 adult CN-AML subjects with CEBPA-bZIP mutation. The nomogram model for leukemia-free survival (LFS) rate was generated by combining genetic abnormalities and clinical data. Risk stratification was conducted based on prognostic variables and the effect of risk-adjusted consolidation therapy was investigated by Kaplan-Meier method. Results:Four variables were finally included in our nomogram model after multivariate Cox analysis,and an equation for risk score calculation was obtained,risk score=1.3002×white blood cell (WBC) (≥18.77×109/L)+1.4065×CSF3R mutation positive+2.6489×KMT2A mutation positive+1.0128×DNA methylation-related genes mutation positive. According to the nomogram model,patients were further divided into low-risk group (score=0,n=46) and high-risk group (score>0,n=95). Prognostic analysis showed that the 5-year LFS rate,5-year overall survival (OS) rate,and 5-year cumulative incidence of relapse (CIR) of patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the high-risk group were 93.5％,97.1％,and 3.5％,while those in patients who received maintenance chemotherapy were 32.9％,70.5％,and 63.4％,respectively. The differences were statistically significant (all P<0.05). Allo-HSCT could significantly improve the prognosis of patients in high-risk group. However,no corresponding benefit was observed in the low-risk group. Conclusion:Adult CN-AML with CEBPA-bZIP mutation has a complex co-mutation pattern. The nomogram model based on mutations of CFS3R,KMT2A and DNA methylation-related genes together with WBC count can further divide this subset of patients into a relatively low-risk group and a relatively high-risk group. For individuals in the high-risk group,allo-HSCT is proposed as post-remission therapy. The above data will benefit the prognosis estimation and treatment decision for adult CN-AML with CEBPA-bZIP mutation.

Objective To investigate the relationship of miRNA gene polymorphisms with blood pressure(BP)responses to the sodium and potassium diet intervention.Methods In 2004,we recruited 514 participants from 124 families in seven villages of Baoji,Shaanxi Province,China.All subjects were given a three-day normal diet,followed by a seven-day low-salt diet,a seven-day high-salt diet,and finally a seven-day high-salt and potassium supplementation.A total of 19 miRNA single nucleotide polymorphisms(SNPs)were selected for analysis.Results Throughout the sodium-potassium dietary intervention,the BP of the subjects fluctuated across all phases,showing a decrease during the low-salt period and an increase during the high-salt period,followed by a reduction in BP subsequent to potassium supplementation during the high-salt diet.MiR-210-3p SNP rs 12364149 was significantly associated with systolic BP(SBP),diastolic BP(DBP)and mean arterial pressure(MAP)responses to low-salt diet.MiR-4638-3p SNP rs6601178 was significantly associated with SBP while miR-26b-3p SNP rs115254818 was significantly associated with MAP responses to low-salt intervention.In addition,miR-26b-3p SNP rs115254818 was significantly correlated with SBP,DBP and MAP responses to high-salt intervention.MiR-1307-5p SNPs rs1 1191676 and rs2292807 were associated with SBP and MAP responses to high-salt diet.MiR-4638-3p SNP rs6601178,miR-210-3p SNP rs12364149,miR-382-5p SNP rs4906032 and rs4143957 were significantly associated with SBP response to high-salt diet.In addition,miR-26b-3p SNP rs115254818 was significantly associated with SBP,DBP and MAP responses to potassium supplementation.MiR-1307-5p SNPs rs11191676,rs2292807,and miR-19a-3p SNP rs4284505 were significantly associated with SBP responses to high-salt and potassium supplementation.Conclusion miRNA gene polymorphisms are associated with BP response to sodium and potassium,suggesting that miRNA genes may be involved in the pathophysiological process of salt sensitivity and potassium sensitivity.

Objective:To investigate the association of serum levels of tumor necrosis factor receptor-related factor 6(TRAF6)and histone deacetylase 3(HDAC3)with severity of coronary artery disease and prognosis in patients with acute myocardial infarction(AMI).Methods:A total of 122 AMI patients admitted Macheng Traditional Chinese Medicine Hospital between July 2019 and December 2020 were selected,divided into low score group(n=73,＜20 points)and high score group(n=49,≥20 points)according to Gensini score.Association of serum levels of TRAF6 and HDAC3 with Gensini score was analyzed by Pearson method.According to survival condition during hospitalization within 28d,they were divided into survival group(n=85)and death group(n=37).Cox regression model was used to analyze the influencing factors for death within 28d in AMI patients;receiver operating charac-teristic(ROC)curve was used to analyze the predictive efficacy of TRAF6 and HDAC3 for death within 28d in AMI patients.Results:Patients in high score group had significant higher serum levels of TRAF6[(6.01±2.39)μg/ml vs.(5.06±1.74)μg/ml,P=0.012]and HDAC3[(4.14±1.94)ng/ml vs.(2.87±1.37)ng/ml,P＜0.001]compared with low score group.Pearson correlation analysis indicated that serum levels of TRAF6 and HDAC3 were positively correlated with Gensini score(r=0.879,0.837,P＜0.001 all).Patients in death group had significant higher serum levels of TRAF6[(6.89±1.67)μg/ml vs.(4.81±1.24)μg/ml,P＜0.001]and HDAC3[(5.37±1.77)ng/ml vs.(2.52±0.76)ng/ml,P＜0.001]compared with those in survival group.Cox regression analysis indicated that Gensini score[HR=1.857,95％CI 1.259～2.737,P=0.001],TRAF6[HR=1.659,95％CI 1.083～2.543,P=0.022],HDAC3[HR=1.779,95％CI 1.192～2.653,P=0.004]were independent risk factors for death within 28d in AMI patients.ROC curve analysis indicated that AUC of TRAF6,HDAC3 and their combina-tion predicting death within 28d in AMI patients was 0.862,0.859 and 0.971 respectively,and AUC of combination was significantly higher than those of TRAF6 and HDAC3 alone(Z=2.535,2.032,P=0.011,0.042).Conclu-sion:Serum levels of TRAF6 and HDAC3 are closely related to severity of coronary artery disease and prognosis in AMI patients,and dual combination possesses good predictive value for prognosis in AMI patients.

Hepatitis E virus(HEV)infection is an infectious disease that can lead to acute or chronic hepatitis E and poten-tially liver failure.HEV can invade multiple organ systems outside the liver,thus leading to pathological damage and diverse clinical manifestations.Neurological disorders are the most common extrahepatic diseases associated with HEV infection.The rare associated extrahepatic diseases include renal disorders,hematological disorders,acute pancreatitis,endocrine system dis-eases,and male infertility.Hence,HEV infection should be considered as a systemic disease rather than solely a liver disease.Many reports have described nervous system diseases caused by HEV infection.This article reviews the rare extrahepatic disea-ses and pathogenic mechanisms of hepatitis E,to enhance comprehensive,in-depth understanding of HEV infection,and to provide a reference for early identification and intervention.

This study primarily investigated the mechanism of Astragalus polysaccharides(APS), a Chinese medicinal material, in regulating the Nrf2/SLC7A11/GPX4 signaling pathway to induce ferroptosis in ovarian cancer cells(Caov-3 and SKOV3 cells). Caov-3 and SKOV3 cells were divided into control(Vehicle) group, APS group, glutathione peroxidase 4 inhibitor(RSL3) group, and APS+RSL3 group. After 48 h of intervention, the activity and morphology of the cells in each group were observed. The cell counting kit-8(CCK-8) method was used to determine the half-maximal inhibitory concentration(IC_(50)), while colony formation and EdU assays were conducted to assess cell proliferation. Biochemical reagents were used to detect lipid reactive oxygen species(L-ROS), malondialdehyde(MDA), divalent iron ions(Fe~(2+)), and glutathione(GSH) in Caov-3 cells. Transmission electron microscopy was employed to observe the morphological changes of mitochondria in Caov-3 cells. Bioinformatics analysis were used to screen potential target genes of APS in ovarian cancer cells. Western blot and RT-PCR were applied to measure the protein and mRNA expression of Nrf2, SLC7A11, and GPX4. The results revealed that APS effectively inhibited the activity and proliferation of ovarian cancer cells, significantly increased the expression levels of L-ROS, MDA, and Fe~(2+)(P<0.001), and significantly reduced the expression level of GSH(P<0.001). Under electron microscopy, the mitochondria of Caov-3 cells appeared significantly smaller, with a marked increase in the density of the bilayer membrane, disappearance of mitochondrial cristae, and rupture of the outer mitochondrial membrane. These effects were more pronounced when APS was combined with RSL3. Bioinformatics screening identified Nrf2, SLC7A11, and GPX4 as potential target genes for APS in ovarian cancer cells. APS was shown to reduce the protein and mRNA expression of Nrf2, SLC7A11, and GPX4(P<0.01), with the APS+RSL3 showing even more significant effects(P<0.001). In conclusion, APS can induce ferroptosis in ovarian cancer cells, and its mechanism may be related to the regulation of the Nrf2/SLC7A11/GPX4 signaling pathway, providing an experimental basis for the use of APS injections in the treatment of ovarian cancer.
Humans ; Ferroptosis/drug effects* ; Female ; NF-E2-Related Factor 2/genetics* ; Ovarian Neoplasms/physiopathology* ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Signal Transduction/drug effects* ; Cell Line, Tumor ; Amino Acid Transport System y+/genetics* ; Polysaccharides/pharmacology* ; Astragalus Plant/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Adenocarcinoma/physiopathology* ; Cell Proliferation/drug effects* ; Glutathione Peroxidase/genetics* ; Reactive Oxygen Species/metabolism*

A precursor ion selection (PIS) based ultra high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-Q-TOF-MS) analytical method was used to screen the chemical components in Jiawei Dingzhi pills (JWDZP) comprehensively and rapidly. To compile the components of the compound medicine, a total of 1 921 components were found utilizing online databases and literature. After verifying the sources, unifying the component names, merging the multi-flavor attributed components, and removing the weak polar molecules, 450 components were successfully retained. The Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 μm) was used, with a 0.1% formic acid water (A)-acetonitrile (B) as the mobile phase. The flow rate was 0.35 mL·min^-1, the column temperature was 35 ℃, and an electrospray ion source was used. Data was collected with the PIS strategy in both positive and negative ion modes. Compounds were screened through matching accurate molecular weight of the database, and identified according to MS/MS data (characteristic fragment ions and neutral loss), with comparison of reference. Some compounds were confirmed using standard products. A total of 176 compounds were screened out in the extract of JWDZP, among which 26 compounds were confirmed by standard products. These compounds include 96 components from the sovereign drug, and 34 coefflux components with low ion intensity. The PIS-UHPLC-Q-TOF-MS/MS method established in this study can quickly and comprehensively screen the chemical components of JWDZP, which enhanced the screening rate of components with co-elution compounds of low ion intensities and provided a basis for the study of the material foundation of JWDZP.