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.

In recent years, China’s capacity for new drug research and development has been significantly strengthened, with major breakthroughs across multiple therapeutic areas, including cancer, autoimmune diseases, and metabolic disorders. An increasing number of domestically developed innovative drugs have been approved for marketing, gradually establishing a competitive position against imported drugs and expanding into global markets. This article systematically reviews the latest research progress of Class 1 innovative drugs in China from 2023 to 2024, categorizes representative approved drugs by therapeutic area, summarizes the clinical advantages and characteristics of representative drugs approved, analyzes in depth the current development trends of and challenges for China’s innovative pharmaceutical industry, and explores future directions, aiming to provide some reference for innovative drug research, industrial development, and policy-making in China.

ObjectiveTo investigate the quality markers of Xiaoqinglong granules（XQLG） for treating bronchial asthma using the analytic hierarchy process（AHP）-entropy weight method（EWM）， network pharmacology and high performance liquid chromatography（HPLC） content determination. MethodsEffectiveness， testability and peculiarity component data of XQLG in treating bronchial asthma were constructed through database retrieval， literature review， and network pharmacology. Subsequently， AHP-EWM was used to quantitatively identify and weight the control layer and element layer， the relevant compounds were selected as candidate quality markers based on comprehensive scores. Further comparison of reference substances and establishment of HPLC content determination method were used to determine the potential quality markers of XQLG， which were verified by molecular docking with disease targets. ResultsA total of 13 components， including glycyrrhizic acid， paeoniflorin， schisandrol A， isoliquiritigenin， 6-gingerol， ephedrine， liquiritin， albiflorin， liquiritigenin， 6-shogaol， pseudoephedrine， cinnamic acid and cinnamaldehyde， were identified as potential quality markers of XQLG by AHP-EWM. Quantitative analysis indicated that all aforementioned quality markers could be detected in 13 batches of XQLG， indicating that it had stable testability as a quality marker. Among these 13 batches of samples， ephedrine and paeoniflorin exhibited good consistency in content， while pseudoephedrine and cinnamaldehyde showed poor consistency. Molecular docking analysis revealed that the 13 compounds exhibited binding energies with the core targets -2.11 kcal·mol^-1， indicating that the 13 compounds could spontaneously bind to the disease targets， which may be the material basis for the treatment of bronchial asthma with XQLG. ConclusionIn this study， 13 compounds were screened by AHP-EWM combined with network pharmacology and HPLC as quality markers for the treatment of bronchial asthma by XQLG， laying the foundation for enhancing the quality standards of this preparation.

In this study, potential quality markers(Q-markers) of Schisandrae Chinensis Fructus for treating bronchial asthma were predicted based on analytic hierarchy process(AHP), entropy weight method(EWM), fingerprint, and network pharmacology. AHPEWM was employed to quantitatively identify the Q-markers of Schisandrae Chinensis Fructus. AHP was used to weight the primary indicators(effectiveness, measurability, and specificity), while EWM was employed to analyze the secondary indicators of each primer indicator. Further, through fingerprint combined with network pharmacology, a ″component-target-pathway″ network was constructed to screen the components of Schisandrae Chinensis Fructus for treating bronchial asthma. It was finally determined that schisandrol A,schisandrin A, and schisandrin B were potential Q-markers of Schisandrae Chinensis Fructus in the treatment of bronchial asthma. This study is the first to comprehensively use AHP-EWM, fingerprint, and network pharmacology to screen the key Q-markers of Schisandrae Chinensis Fructus in the treatment of bronchial asthma. This study provides a scientific basis for improving the quality standard of Schisandrae Chinensis Fructus and lays a foundation for studying its material basis in treating bronchial asthma.
Schisandra/chemistry* ; Asthma/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Network Pharmacology ; Humans ; Entropy ; Lignans/analysis* ; Fruit/chemistry* ; Quality Control ; Cyclooctanes ; Polycyclic Compounds/analysis*

To clarify the species, pathogenicity, and distribution of the pathogens causing the root rot of Atractylodes lancea in Hubei province, the tissue separation method was used to isolate the pathogens from root rot samples in the main planting areas of A. lancea in Hubei. Based on the preliminary identification of the Fusarium genus by the internal transcribed spacer(ITS) sequence, three housekeeping genes, EF1/EF2, Btu-F-FO1/Btu-F-RO1, and FF1/FR1, were amplified and sequenced. Subsequently, a phylogenetic tree was constructed based on these TEF gene sequences to classify the pathogens. The pathogenicity of these strains was determined using the root irrigation method. A total of 194 pathogen strains were isolated using the tissue separation method. Molecular identification using the three housekeeping genes identified the pathogens as F. solani, F. oxysporum, F. commune, F. equiseti, F. tricinctum, F. redolens, F. fujikuroi, F. avenaceum, F. acuminatum, and F. incarnatum. Among them, F. solani and F. oxysporum were the dominant strains, widely distributed in multiple regions, with F. solani accounting for approximately 54% of the total isolated strains and F. oxysporum accounting for approximately 34%. Other strains accounted for a relatively small proportion, totaling approximately 12%. The results of pathogenicity determination showed that there were certain differences in pathogenicity among strains. The analysis of the pathogenicity differentiation of the widely distributed F. solani and F. oxysporum strains revealed that these dominant strains in Hubei were mainly highly pathogenic. This study determined the species, pathogenicity, and distribution of the pathogens causing the root rot of A. lancea in Hubei province. The results provide a scientific basis for further understanding the root rot of A. lancea and its epidemic occurrence and scientifically preventing and controlling this disease.
Plant Diseases/microbiology* ; Atractylodes/microbiology* ; Phylogeny ; Plant Roots/microbiology* ; Fusarium/classification* ; China ; Virulence ; Fungal Proteins/genetics*

Ginkgo biloba, an ancient relict plant, holds a lengthy medicinal tradition in China. The leaves and seeds of this remarkable species contain flavonoids, a class of active compounds that offer a multitude of pharmacological advantages. The understanding of the synthesis process of these flavonoids can be deepened substantially by elucidating their biosynthetic pathway and metabolic regulation mechanisms. This can thereby provide a foundation for achieving precise regulation of flavonoid biosynthesis, which is of great significance for improving the production efficiency and quality of flavonoids in G. biloba. This review comprehensively summarizes research advancements in metabolomics, genomics, and transcriptomics of flavonoids in G. biloba, aiming to establish a thorough academic framework. It examines key enzymes in the biosynthetic pathway of flavonoids in G. biloba and their functions, highlighting their crucial roles in flavonoid production. Additionally, it outlines transcriptional regulation mechanisms associated with flavonoid in G. biloba biosynthesis, focusing on transcription factors responsive to environmental cues and their regulatory networks that modulate flavonoid gene expression. These insights offer a theoretical foundation for precise control of G. biloba flavonoid production. By amalgamating these diverse research findings, this review aims to establish a robust theoretical groundwork for future studies on biosynthesis and efficient utilization of flavonoids in G. biloba.
Ginkgo biloba/chemistry* ; Flavonoids/biosynthesis* ; Gene Expression Regulation, Plant ; Plant Proteins/genetics* ; Biosynthetic Pathways

Drug addiction, a disorder characterized by chronic relapse and compulsive drug use, poses a significant threat to public safety and human health. Addictive substances can be categorized as natural, semi-synthetic, or synthetic based on their origin. Additionally, they can be classified into three groups according to their pharmacological targets: opioids, hallucinogens, and cannabinoids that act on G-protein-coupled receptors (GPCRs); alcohols, nicotine, ketamine, barbiturates, and benzodiazepines (BDZs) that affect ligand-gated ion channel-type receptors; and psychostimulants that interact with monoamine transporters. Current treatments for drug addiction primarily include substitution therapy and non-pharmacological approaches. However, these methods have limitations, particularly in addressing the underlying causes of relapse. Several drugs in clinical trials have demonstrated potential therapeutic effects for addiction to opioids, heroin, cocaine, and other substances. This review examines the origins and pharmacological mechanisms of addiction to naturally-derived psychoactive substances (NPS) and provides an overview of recent advancements in pharmacotherapy for drug addiction.
Humans ; Substance-Related Disorders/drug therapy* ; Psychotropic Drugs/therapeutic use* ; Animals

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

OBJECTIVES: This study explores the differences in fluid flow within alveolar cancellous bone at various sites under orthodontic forces and elucidates the relationship between fluid shear stress and bone remodeling. These fin-dings lay the groundwork for understanding the biomechanical mechanisms of orthodontic tooth movement. METHODS: Stress relaxation tests were performed on human alveolar bone samples to determine material parameters by using the Prony series. An inverse model of alveolar bone was then developed for numerical simulations of fluid-structure interactions to calculate fluid flow within cancellous bone. Meanwhile, a rat model of tooth movement was established to investigate variations in bone remodeling speeds across different regions. RESULTS: The microstructural distribution of cancellous alveolar bone was similar in humans and rats. The bone volume fraction and trabecular thickness gradually decreased from root cervical region to root apical region, while the trabecular space gradually increased. Under the influence of orthodontic forces, fluid shear stress within cancellous bone showed spatial variability across different levels, with the highest shear stress occurring at the root apical region, ranging from 0 to 0.936 6 Pa. Additionally, the rat model of tooth movement indicated that bone remodeling occurred more rapidly at the root apical region. CONCLUSIONS Fluid stimulation has a remarkable effect on al-veolar bone remodeling, causing changes in the structure of alveolar bone and ultimately regulating the speed of structu-ral remodeling.
Bone Remodeling ; Animals ; Tooth Movement Techniques ; Rats ; Alveolar Process/physiology* ; Stress, Mechanical ; Humans ; Biomechanical Phenomena ; Cancellous Bone/physiology* ; Shear Strength