Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

ObjectiveTo evaluate the therapeutic effect of Shenji Guben prescription （SJGB） on chronic obstructive pulmonary disease （COPD） in mice and to explore its potential therapeutic mechanism via transcriptomics. MethodsA mouse model of COPD was established by combined exposure to lipopolysaccharide （LPS） and cigarette smoke. C57BL/6J mice were randomly allocated into a control group， a model group， an acetylcysteine （78 mg·kg^-1·d^-1） group， and low- （7.5 g·kg^-1·d^-1）， medium- （15 g·kg^-1·d^-1）， and high-dose （30 g·kg^-1·d^-1） SJGB groups. After 13 weeks of modeling， oral administration was initiated and continued for 28 days. The therapeutic effects of SJGB were assessed based on body weight， lung function， lung tissue pathology， and inflammatory factors in bronchoalveolar lavage fluid （BALF）. Ultra-high performance liquid chromatography-tandem mass spectrometry （UHPLC-MS/MS） was employed to identify the active ingredients in SJGB. Transcriptomic profiling of lung tissue was performed by RNA-seq to identify differentially expressed genes （DEGs）， followed by gene ontology （GO） enrichment analysis， Kyotoencyclopedia of Genes and Genomes （KEGG） enrichment analysis， Gene Set Enrichment Analysis （GSEA）， and protein-protein interaction （PPI） network construction. Key genes were further validated by Western blot and Real‑time polymerase chain reaction （Real-time PCR）. ResultsAfter drug intervention， the final body weights of mice in medium- and high-dose SJGB groups were higher than those in the model group （P<0.05）. Compared with the model group， SJGB groups demonstrated a significant decrease in expiratory time （Te）， along with increases in peak expiratory flow （PEF）， 50% expiratory flow （EF50）， tidal volume （TV）， and expiratory volume （EV） （P<0.05）. High-dose SJGB ameliorated pathological changes in the lung tissue， reduced peribronchial inflammation scores， and decreased mean linear intercept （MLI） （P<0.01）. Compared with the model group， medium- and high-dose SJGB groups showed reductions in interleukin-6 （IL-6） and interleukin-1β （IL-1β） levels （P<0.01）. UHPLC-MS/MS revealed that the five most abundant components in SJGB were （S）-actinidine， ephedrine， pyroglutamic acid， methylephedrine， and coumarin. Transcriptomic analysis revealed 219 DEGs regulated by SJGB， suggesting that the anti-COPD effects of SJGB may be mediated through key genes such as cluster of differentiation 68 （CD68）， integrin subunit alpha X （ITGAX）， and cathepsin S （CTSS）， primarily involved in the lysosomal pathway. Western blot and Real-time PCR results confirmed that SJGB inhibited the expression of CD68， ITGAX， and CTSS compared with the model group （P<0.05）. ConclusionSJGB effectively improved the lung function and attenuated lung tissue inflammation in the mouse model of COPD by modulating the lysosomal pathway and related genes including CD68， ITGAX， and CTSS.

Objective: To analyze the factors affecting direct-acting antiviral (DAA) therapy among cases with hepatitis C virus (HCV) infection in Zhejiang Province, so as to provide evidence for optimizing local HCV prevention and treatment strategies and improving DAA treatment coverage. Methods: Eight counties (cities, districts) in Zhejiang Province were selected as survey sites. Consecutive sampling was used to enroll HCV cases reported from November 2022 to June 2024. Demographic information, diagnosis and treatment status, DAA therapy, and awareness of relevant medical insurance policies were collected through questionnaire surveys. Factors affecting DAA therapy among cases with HCV infection were analyzed using a multivariable logistic regression model. Results: A total of 412 questionnaires were distributed, and 404 valid questionnaires were collected, with an effective rate of 98.06%. There were 291 males (72.03%) and 113 females (27.97%). The median age was 49.00 (interquartile range, 11.00) years. A total of 303 cases received DAA therapy, with a proportion of 75.00%. Multivariable logistic regression analysis showed that HCV cases aged 40-<50 years (OR=3.469, 95%CI: 1.228-9.345) and with per capita monthly household income >3 000 yuan (>3 000-5 000 yuan, OR=3.198, 95%CI: 1.597-6.403; >5 000 yuan, OR=5.391, 95%CI: 2.230-13.033) had higher likelihood of receiving DAA therapy. HCV cases diagnosed in non-infectious disease departments (OR=0.334, 95%CI: 0.173-0.643), concerned about economic burden of DAA therapy (OR=0.309, 95%CI: 0.160-0.599), and unaware of HCV payment policy by disease type (OR=0.262, 95%CI: 0.111-0.622) had lower likelihood of receiving DAA therapy. Conclusions The proportion of DAA therapy among cases with HCV infection in Zhejiang Province is relatively high. Age, per capita monthly household income, department of diagnosis, concerns about DAA therapy, and medical insurance/payment policies are factors influencing DAA therapy among cases with HCV infection.

To introduce the general thinking, guidelines, work objectives and elaboration process of the general technical requirements adopted by volume Ⅳ of the Chinese Pharmacopoeia 2025 Edition, and to summarize and figure out the main characteristics on dosage forms, physico-chemical testing, microbial and biological testing, reference standards and guidelines The newly revised general chapters of pharmacopoeia give full play to the normative and guiding role of the Chinese Pharmacopoeia standard, track the frontier dynamics of international drug regulatory science and the elaboration of monographs, expand the application of state-of-the-art technologies, and steadily promote the harmonization and unification with the ICH guidelines； further enhance the overall capacity of TCM quality control, actively implement the 3 R principles on animal experiments, and practice the concept of environmental-friendly； replace and/or reduce the use of toxic and hazardous reagents, strengthen the requirements of drug safety control This paper aims to provide a full-view perspective for the comprehensive, correct understanding and accurate implementation of general technical requirements included in the Chinese Pharmacopoeia 2025 Edition.

Objective: To provide reference for the correct understanding and accurate implementation of the general chapters of physical and chemical analysis in the Chinese Pharmacopoeia 2025 Edition Volume Ⅳ.
Methods: Introduce the main characteristics and content of the additions and revisions of the general chapters of physical and chemical analysis in the Chinese Pharmacopoeia 2025 Edition Volume Ⅳ.
Results: The general chapters of physical and chemical analysis in the Chinese Pharmacopoeia 2025 Edition are more harmonized with the relevant guidelines of the ICH Q series, and the inclusion of advanced and mature instrument analysis technology standards and analysis method standards related to drug safety, efficacy, and quality controllability is further increased.
Conclusion: The general chapters of physical and chemical analysis in the Chinese Pharmacopoeia 2025 Edition have provided a more convenient new bridge for China’s drugs to go international, standardized testing technology support for achieving full process quality control, and better meet the needs of drug research and development, production, quality control, and supervision in China.

To introduce the general thinking,guidelines,work objectives and elaboration process of the general technical requirements adopted by volume Ⅳ of the Chinese Pharmacopoeia 2025 Edition,and to summarize and figure out the main characteristics on dosage forms,physico-chemical testing,microbial and biological testing,ref-erence standards and guidelines.The newly revised general chapters of pharmacopoeia give full play to the norma-tive and guiding role of the Chinese Pharmacopoeia standard,track the frontier dynamics of international drug regu-latory science and the elaboration of monographs,expand the application of state-of-the-art technologies,and stead-ily promote the harmonization and unification with the ICH guidelines;further enhance the overall capacity of TCM quality control,actively implement the 3 R principles on animal experiments,and practice the concept of environ-mental-friendly;replace and/orreduce the use of toxic and hazardousreagents,strengthen the requirementsofdrug safety control.This paper aims to provide a full-view perspective for the comprehensive,correct understanding and accurate implementation of general technical requirements included in the Chinese Pharmacopoeia 2025 Edition.

Objective:To provide reference for the correct understanding and accurate implementation of the general chapters of physical and chemical analysis in the Chinese Pharmacopoeia 2025 Edition Volume Ⅳ.Methods:Intro-duce the main characteristics and content of the additions and revisions of the general chapters of physical and chemical analysis in the Chinese Pharmacopoeia 2025 Edition Volume Ⅳ.Results:The general chapters of physi-cal and chemical analysis in the Chinese Pharmacopoeia 2025 Edition are more harmonized with the relevant guide-lines of the ICH Q series,and the inclusion of advanced and mature instrument analysis technology standards and analysis method standards related to drug safety,efficacy,and quality controllability is further increased.Conclusion:The general chapters of physical and chemical analysis in the Chinese Pharmacopoeia 2025 Edition have provided a more convenient new bridge for China's drugs to go international,standardized testing technology support for achieving full process quality control,and better meet the needs of drug research and development,production,quality control,and supervision in China.

Numerous c-mesenchymal-epithelial transition(c-MET)inhibitors have been reported as potential anticancer agents.However,most fail to enter clinical trials owing to poor efficacy or drug resistance.To date,the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed.In this study,we constructed the largest c-MET dataset,which included 2,278 molecules with different struc-tures,by inhibiting the half maximal inhibitory concentration(IC50)of kinase activity.No significant differences in drug-like properties were observed between active molecules(1,228)and inactive mol-ecules(1,050),including chemical space coverage,physicochemical properties,and absorption,distri-bution,metabolism,excretion,and toxicity(ADMET)profiles.The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding(t-SNE)high-dimensional data.Further clustering and chemical space networks(CSNs)analyses revealed commonly used scaffolds for c-MET inhibitors,such as M5,M7,and M8.Activity cliffs and structural alerts were used to reveal"dead ends"and"safe bets"for c-MET,as well as dominant structural fragments consisting of pyr-idazinones,triazoles,and pyrazines.Finally,the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules,including at least three aromatic het-erocycles,five aromatic nitrogen atoms,and eight nitrogen-oxygen atoms.Overall,our analyses revealed potential structure-activity relationship(SAR)patterns for c-MET inhibitors,which can inform the screening of new compounds and guide future optimization efforts.