Ductular reaction （DR） refers to the adaptive pathological changes that occur after hepatobiliary injury， and it is essentially a repair response involving the proliferation， fibrosis， and inflammation of biliary epithelial cell （BEC）. With the understanding of the biological function of BEC， the potential value of DR in disease prognosis and treatment has gradually become a research hotspot. This article systematically reviews the molecular mechanism of DR， its potential as a therapeutic target， and future development directions， as well as novel therapies suggested by targeting these molecular mechanisms， in order to provide a new direction for overcoming current bottlenecks in the treatment of bile duct diseases.

OBJECTIVE To explore the ameliorative effect of Tiaozhi Xiaoban Mixture on atherosclerosis and the potential role of long non-coding RNA(Linc RNA)in anti-atherosclerosis.METHODS A model of atherosclerosis was established in SD rats subjec-ted to a high-fat diet.At 4 weeks post-modeling,thoracic aortic tissues from atherosclerotic rats were collected for hematoxylin-eosin(HE)staining to systematically evaluate the anti-atherosclerotic effects of Tiaozhi Xiaoban Mixture at different doses.Biochemical kits were utilized to assess relevant indices related to blood lipid levels as well as liver and kidney function,thereby evaluating the impact of Tiaozhi Xiaoban Mixture on these parameters.Enzyme-linked immunosorbent assay(ELISA)was employed to measure serum inflam-mation markers influenced by Tiaozhi Xiaoban Mixture.Additionally,TUNEL staining and Western blot analysis were conducted to ex-amine the apoptotic effects of Tiaozhi Xiaoban Mixture on thoracic aorta tissue.Finally,qPCR was used to detect the expression levels of Line-HC,MALAT1,etc.,in order to evaluate how Tiaozhi Xiaoban Mixture affecting these specific RNA molecules.RESULTS Following treatment with Tiaozhi Xiaoban Mixture,the blood lipid profiles indicated that total cholesterol(TC),triglycerides(TG),and low-density lipoprotein cholesterol(LDL-C)were significantly down-regulated(P＜0.05,P＜0.01),while high-density lipopro-tein cholesterol(HDL-C)levels were up-regulated in the atherosclerotic rats.Moreover,serum levels of liver and kidney function markers such as aspartate aminotransferase(AST),alanine aminotransferase(ALT),blood urea nitrogen(BUN),and creatinine(Cr)exhibited down-regulation(P＜0.05,P＜0.01).Additionally,pro-inflammatory factors including interleukin-6(IL-6),interleukin-1 beta(IL-1β),tumor necrosis factor-alpha(TNF-α),high-sensitivity C-reactive protein(hs-CRP),and matrix metallopeptidase 9(MMP-9)were also reduced(P＜0.01),whereas the anti-inflammatory factor interleukin-10(IL-10)was found to be elevated(P＜0.01).Furthermore,after oral administration of Tiaozhi Xiaoban Mixture,expression levels of apoptosis-related factors NLRP3,ASC,Cleaved Caspase-1,Cleaved IL-1 β,Puma,Bax,Noxa,and MDM2 in thoracic aorta tissues from the atherosclerotic rats showed sig-nificant down-regulation(P＜0.05,P＜0.01).Notably,following treatment with Tiaozhi Xiaoban Mixture,mRNA levels of Linc-HC decreased while mRNA expression of MALAT1 increased(P＜0.05,P＜0.01).CONCLUSION Tiaozhi Xiaoban Mixture may inhibit the expression of Linc-HC and up-regulate the expression of MALAT1 to reduce the formation of atherosclerotic plaque,improve ab-normal blood lipids and liver and kidney function,alleviate inflammation and inhibit apoptosis.

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.

ObjectiveThe significance of adverse childhood experiences (ACEs) among men who have sex with men (MSM) should not be overlooked. This study aims to assess the reliability and validity of the Chinese version of the Adverse Childhood Experiences-International Questionnaire (ACE-IQ) among the MSM population in China to evaluate its applicability in this group. MethodsA cross-sectional survey was conducted in three Chinese cities(Shanghai, Shenyang and Kunming) using snowball sampling, with a total of 1 130 MSM participants included. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to assess the structural validity of the scale. Internal consistency reliability was evaluated using Cronbach’s α coefficient, and split-half reliability was assessed with the Spearman-Brown coefficient. ResultsAccording to the EFA results, after removing item ACE10 (“parental death”), the 23-item ACE-IQ demonstrated a six-factor structure, including victimization or witnessing emotional/physical abuse, sexual abuse, physical neglect, family dysfunction, emotional neglect, and peer violence. CFA results indicated a good model fit for the six-factor model, supporting the EFA findings. The scale demonstrated good reliability, with a Cronbach's α coefficient of 0.852 and a Spearman-Brown coefficient of 0.899, indicating high internal consistency and split-half reliability within the studied population. ConclusionThe Chinese version of the ACE-IQ demonstrates satisfactory reliability and validity among MSM population, supporting its suitability for assessing ACEs in this group. The findings provide an empirical basis for subsequent mental health interventions.

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

Objective:To investigate the influence of 17β-estradiol(17β-E2)in the proliferation and differentiation capabilities of primary cultured hippocampal neural stem cells(NSCs),and to clarify its potential mechanism.Methods:The NSCs were isolated from the hippocampal tissue of SD rats within 24 h of birth,and divided into control group and 17β-E2 group.Immunofluorescence method was used to detect the expressions of Nestin and 5-ethynyl-2'-deoxyuridine(EdU)in NSCs in two groups,and the proliferation rates of NSCs were calculated.Western blotting method was used to detect the expression level of Nestin protein.Flow cytometry was used to analyze the percentages of NSCs at different cell cycles.Immunofluorescence method was used to identify the expressions of markers for neurons β Ⅲ-tubulin and astrocyte marker glial fibrillary acidic protein(GFAP)in the NSCs after differentiation,and the relative ratio of neurons to astrocytes was calculated.Western blotting method was used to detect the expression levels of β Ⅲ-tubulin and GFAP proteins as well as phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt),phosphorylated Akt(p-Akt),glycogen synthase kinase-3 beta(GSK-3β),phosphorylated GSK-3β(p-GSK-3β),and beta-catenin(β-catenin)proteins related to PI3K/Akt/GSK-3β pathway.Results:Immunofluorescence assay revealed positive Nestin expression in NSCs in two groups;compared with control group,the proliferation rate of NSCs in 17β-E2 group was increased(P＜0.01).Compared with control group,the expression level of Nestin protein in the NSCs in 17β-E2 group was increased(P＜0.05),and the percentage of NSCs in S phase was increased(P＜0.01).Compared with control group,the relative ratio of neurons to astrocytes in 17β-E2 group was significantly increased(P＜0.05).After differentiation,compared with control group,the expression level of β Ⅲ-tubulin protein in the NSCs in 17β-E2 group was increased(P＜0.05),and the expression level of GFAP protein was decreased(P＜0.01),while the expression levels of Akt,p-Akt,β-catenin,and p-GSK-3β proteins were increased(P＜0.05 or P＜0.01),and the expression level of GSK-3β protein was decreased(P＜0.05).Conclusion:17β-E2 can promote the proliferation of NSCs and facilitate their differentiation towards neurons,and its mechanism may be related to the PI3K/Akt/GSK-3β signaling pathway.

OBJECTIVE To establish a population pharmacokinetic(PopPK)model to predict the PK characteristics of GLS-010 in humans.METHODS Fifty-eight cynomolgus monkeys were used,18 of which were randomly divided into three groups and received a single intravenous infusion of GLS-010 at doses of 2,6,and 18 mg·kg-1,respectively.The rest were randomly assigned to four groups and received multiple intravenous infusions of GLS-010 at doses of 0,5,25,and 100 mg·kg-1,respectively,once a week(quaque week,qw)for five consecutive weeks.Blood samples were collected before and after administration.The concentrations of GLS-010 in the monkey serum were measured using a validated enzyme-linked immunosorbent assay,while those of anti-drug antibodies(ADA)in the cynomolgus monkey serum were determined by ultra-sensitive electrochemiluminescence immunoassay.The PK data on GLS-010 in cynomolgus monkeys was obtained,and the drug-time curves were plotted.A PopPK model was constructed using non-compartmental analysis and evaluated by goodness-of-fit plots and visual predictive checks.The constructed PopPK model was used to predict the PK characteristics in humans,which were finally compared with actual Phase Ⅰ clinical study results for validation.RESULTS The predictive results of the PopPK model were highly consistent with the actual Phase Ⅰ clinical study results.The model was able to predict the human PK characteristics under various dosing regimens,including 1 mg·kg-1 quaque 2 weeks(q2w),4 mg·kg-1(q2w),240 mg(q2w),240 mg(q3w),and 10 mg·kg-1(q2w).The predicted maximum plasma concentrations(Cmax)were 24.8,99.1,85.0,85.0,and 247.8 mg·L-1,respectively,and the AUC0-336h was 4 902.0,20 060.0,17 147.7,22 145.7(AUC0-504h),and 50 817.6 mg·h·L-1,respectively.The safety risks for the corresponding dosing regimens were 47.3,11.6,13.5,10.5,and 4.6,respectively.The predicted receptor occupancy at steady state(ROss)at Cmax,average plasma concentration(Cavg),and minimum plasma concentration(Cmin)were 38.8％,72.7％,69.4％,64.1％and 87.2％,29.1％,63.8％,60.0％,49.8％and 82.1％,21.9％,55.5％,51.3％,36.3％and 76.7％,respectively.CONCLUSION The PopPK model can effectively predict the human PK characteristics under different dosing regimens with high consistency with actual Phase Ⅰ clinical study results,which can serve as an important reference for selection of safe and effective doses for first-in-human research.

This study investigated the drug resistance and genetic relationships among strains co-existing in animals,the environ-ment,and the living quarters of employees at large-scale pig farms in certain regions of Shandong Province,to provide a scientific ba-sis for elucidating the transmission mechanisms of drug-resistant bacteria through bacterial traceability analysis.Samples were col-lected from two pig farms,and bacteria were isolated and purified.The species of the isolated strains were identified via 16S rRNA gene sequencing.Antimicrobial susceptibility testing was conducted with a VITEK-2 Compact system and the disk diffusion method for strains present in pigs,the environment,and living areas.Furthermore,whole-genome sequencing was performed on the Illumina Miniseq platform to annotate drug resistance genes,and multilocus sequence typing(MLST)and core genome single nucleotide poly-morphism(cgSNP)analyses were used to trace the resistant strains.Three species—Staphylococcus aureus,Pseudomonas aeruginosa,and Bacillus cereus—were isolated and cultured from animals,the environment,and employee living areas,and their distributions were analyzed.These strains exhibited diverse drug resistance spectra and genetic diversity.Additionally,the strains displayed highly consistent resistance profiles,resistance genes,ST types,and SNP loci in pig urine,soil both inside and outside the facility,human drinking water,and the cafeteria and dormitories.Our findings indicated a potential risk of transmission of opportunistic pathogens be-tween the pig farming area and the living quarters.Particular attention should be paid to the environmental transmission of methicillin-resistant Staphylococcus aureus.