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.

The auxin/indole-3-acetic acid (Aux/IAA) gene family is an important regulator for plant growth hormone signaling, involved in plant growth, development, as well as response to environmental stresses. In the present study, we identified SmIAA7 which is potentially associated with Salvia miltiorrhiza leaf development through comparatively analyzed the transcriptome data from different pinnate leaves. SmIAA7 was successfully isolated from S. miltiorrhiza using the specific primers. Then subsequent bioinformatic analysis, prokaryotic expression and purification, subcellular localization, and induction expression analysis under auxin and abiotic stress were performed. The full-length of SmIAA7 contained an ORF of 684 bp encoding a protein of 227 amino acid with a molecular weight of 25.3 kD. Conserved domain analysis showed that SmIAA7 contains the conserved Aux_IAA domain (pfam02309). Sequence analysis and phylogenetic tree analysis results indicated SmIAA7 was phylogenetically close to IAA7 and IAA14 from other plants, suggesting SmIAA7 involved in plant growth and development as well as response to environmental stresses. The prokaryotic expression vector pET28a-SmIAA7 was constructed and SmIAA7 recombinant protein was successfully expressed in E. coli Rosetta (DE3) strain. Subcellular localization experiment demonstrated that SmIAA7 localized in the nucleus of plant cells. Real-time fluorescence quantitative PCR results showed that the expression level of SmIAA7 was upregulated in response to auxin. Drought, low temperature, and salt stress significantly increased the transcript level of SmIAA7 gene. This study lays a foundation for further elucidating the role of SmIAA7 in leaf development, signal transduction, and stress defense in S. miltiorrhiza.

Objective To explore the genes related to the pathogenesis of polycystic ovary syndrome(PCOS)through bioinformatics methods and verify them in ovarian granulosa cells,providing a reference for screening potential molecular markers of PCOS.Methods The GSE34526 and GSE137684 datasets were re-spectively used as the training set and validation set.The inflammation-related genes potentially associated with the onset of PCOS were explored through differential expression analysis and weighted gene co-expres-sion network analysis.Subsequently,their predictive value was verified through the receiver operating charac-teristic(ROC)curve.Thirty patients with PCOS(the PCOS group)and 27 patients without PCOS(the con-trol group)who were treated in Affiliated Hospital of Youjiang Medical University for Nationalities were se-lected as the research objects.RT-qPCR was applied to verify the expression level of core genes in granular cells.Spearman correlation and multiple linear regression were used to analyze the correlation between the ex-pression level of core genes and various clinical parameters,and the ROC curve was used to analyze the diag-nostic efficacy of the expression level of core genes for PCOS.Finally,the protein expression level of core genes was verified on animal models.Results A total of 1 888 differentially expressed genes,89 module-relat-ed genes and 366 inflammatory response-related genes were identified.The core gene phosphatidylinositol-4,5-diphosphate 3-kinase catalytic subunit γ(PIK3CG)was ultimately obtained by taking co-expressed genes and verifying with the ROC curve.RT-qPCR results showed that the expression level of PIK3CG in granulosa cells of the PCOS group was higher than that of the control group(P<0.05).Spearman correlation analysis showed that the expression level of PIK3CG was positively correlated with BMI,testosterone(T),fasting in-sulin(FINS),and insulin resistance index(HOMA-IR,P<0.05).Multivariate linear regression analysis showed that FINS,HOMA-IR and BMI were increased with the increasing of PIK3CG expression level(P<0.05).ROC curve analysis showed that the area under the curve for diagnosing PCOS patients with PIK3CG mRNA expression levels in granulosa cells was 0.659 3.The immunohistochemical results showed that the ex-pression of PIK3CG protein in the ovarian tissues of mice in the PCOS group was significantly increased.Con-clusion PIK3CG may be potentially associated with the pathogenesis of PCOS.

Objective To identify and delineate the developmental trajectories of depressive symptoms in the middle-aged and elderly population in China,and to explore the risk factors for depressive symptom trajectories in China's middle-aged and elderly population.Methods According to our inclusion and exclusion criteria,7 600 participants were subjected based on the data from the China Health and Aged Care Tracking Survey(CHARLS)published by Peking University.The data from 5 waves of the survey from 2011 to 2023 were collected and analyzed with latent growth curve model(LGCM),latent class growth model(LGCM)to identify the developmental trajectories of depressive symptoms in the participants.Multicategorical logistic regression analyses were conducted to analyze whether gender,marital status,educational level,urban/rural residence,annual income,self-rated health status,and childhood bullying experience were risk factors for different trajectories of depressive symptoms.Results Two developmental trajectories of depressive symptoms were identified and classified in this study,that is,low-level stable(n=5 545,72.96%)and high-level ascending(n=2 055,27.04%).With the low-level stable group as a reference,multicategorical logistic regression analysis revealed that female(OR=1.373,95CI%:1.191～1.584,P<0.001),residence of rural area(OR=1.634,95CI%:1.410～1.895,P<0.001),and poor self-rated health status(OR=2.059,95%CI:1.890～2.243,P<0.001),and experience of childhood bullying(OR=1.76,95%CI:1.489～2.080,P<0.001)were associated with an increased risk of high-level ascending trajectory of depression.Conclusion There are 2 different trajectories of depressive mood in Chinese middle-aged and elderly population.And poor self-rated health status,history of childhood bullying,being female,and residence of rural area are risk factors for a high-level ascending trajectory of depressive symptoms.

Objective To evaluate the application of shear wave elastography(SWE)in the diagnosis of peripheral neuropathy in patients with diabetes.Methods Totally 85 patients with type 2 diabetes(T2DM)were selected from the Chengdu Office Hospital of People's Government of Tibetan Autonomous Region,including 46 patients with peripheral neuropathy(DPN)and 39 patients without peripheral neuropathy(NDPN).Compared for clinical data(gender,age,disease duration),cross-sectional area of the median nerve measured by high-frequency ultra-sound(CSA)and shear wave elastography(SWE)parameters(mean Young's modulus value,Emean)and shear wave velocity(SWV)between two groups of patients.Multifactor Logistic regression analysis was carried out on the indicators between the above groups to screen independent predictors in the diagnosis of peripheral neuropathy in diabetes patients,and a combined model was constructed.The area under the operating characteristic curve(AUC),sensitivity and specificity of the subjects were used to evaluate the diagnostic efficacy of the single model and com?bined model of the quantitative parameters(CSA,Emean,SWV)measured by clinical data,high?frequency ultra?sound and SWE in the diagnosis of peripheral neuropathy in diabetes patients.Results Age,course of disease,Emean,SWV and CSA were statistically significant in the diagnosis of peripheral neuropathy in diabetes patients(all P<0.05).AUC was 0.658,0.754,0.839,0.822 and 0.736,respectively.The combination model based on disease course,CSA and SWV showed the highest diagnostic efficiency,with AUC,sensitivity,and specificity of 0.887(0.800-0.946),80.43％,and 84.62％,respectively.Conclusions The combined model based on the course of disease,CSA and SWV have a high diagnostic efficiency in peripheral neuropathy of diabetes patients,and has good clinical application value.

Depressive disorder is a kind of mental disorder characterized by persistent and significant depressed mood, with complex etiology and high recurrence rate. At present, more precise and effective diagnostic and therapeutic approaches are still required. Increasing evidence suggests that hypoxia inducible factor-1 (HIF-1) and related pathways are involved in regulating the development and recovery of depression. HIF-1 enhances neuroplasticity, mitigates neuroinflammatory responses, alleviates oxidative stress, and modulates brain energy metabolism by influencing specific molecules associated with depression. This paper reviews pertinent domestic and international studies, examine the potential mechanisms of HIF-1 in the pathogenesis and progression of depression, and explore antidepressant treatment strategies targeting the HIF-1 signaling pathway. This article provides novel insights into elucidating the pathogenesis of depression and developing innovative therapeutic approaches.

Objective To investigate the characteristics of changes in pain-anxiety-depression-fatigue symptom clusters and their possible associated factors in adolescents with acute lymphoblastic leukemia(ALL)during early chemotherapy.Methods A prospective longitudinal study was conducted from Nov 2019 to Oct 2021,enrolling newly diagnosed adolescent ALL patients from 5 tertiary or pediatric specialty hospitals in Shanghai,Zhejiang Province,Sichuan Province,Anhui Province and Guangdong Province.Patient-reported pain,anxiety,depression,and fatigue were collected at five time points within the first nine weeks of chemotherapy using the PROMIS Pediatric-25 instrument.Latent profile analysis(LPA)and latent transition analysis(LTA)were applied to explore the latent classes of symptom clusters,their transition probabilities over time,and possible risk or protective factors associated with class membership.Results A total of 134 ALL cases were enrolled,and symptom clusters at all the 5 time points(T1-T5)were consistently classified into three groups of mild,moderate and severe symptoms.The severe symptoms group accounted for the largest proportion at each time point(54.5%,59.7%,66.4%,49.3%,and 47.0%,respectively),while the mild and moderate symptoms groups showed an initial decline followed by an increase.Among participants,40.2%maintained the same symptom status,and 77.4%experienced at least one episode of severe symptom status during the trajectory.Religious affiliation(T5)and family monthly income>5 000 Yuan(T2,T4 and T5)served as protective factors against severe symptoms.Higher baseline fatigue(T1)was associated with membership in the severe symptoms group at subsequent time points.Conclusion Pain-anxiety-depression-fatigue symptoms in adolescents with ALL during early chemotherapy can be categorized into mild,moderate and severe symptoms with dynamic transitions over time.Higher baseline fatigue was associated with increased risk of severe symptoms,whereas higher family income and religious affiliation appeared protective effects.

With the trend of population aging, the number of patients with comorbidities is increasing, who are the main subjects of general practice service in general hospitals. Tongji Hospital created a new service model and opened a multidisciplinary outpatient clinic based on general practice department (MDT general practic clinic) for patients with comorbidities in December 2021, which has improved the clinical outcomes, and the medical experience and satisfaction of patients. This article elaborates on the organizational structure, team building, and operational process of the MDT general practice clinic for comorbidities; analyzes the characteristics of patients and the implementation effects, to provide a reference for comorbidity patient service in general hospitals.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

Major depressive disorder (MDD) is a common mental disorder characterized by long-term low mood, anhedonia, and may even lead to suicidal behavior. The development and progression of MDD involves a range of pathological alterations in the central nervous system, including dysfunction of synaptic transmission, hyper-activation of neuroinflammation, and diminished neurogenesis. The transient receptor potential vanilloid 1 (TRPV1) channel is highly expressed in brain regions associated with depression, and can regulate physiological activities such as neuroinflammation, neurogenesis, and synaptic transmission efficacy. Hence, the TRPV1 channel should be implicated in the pathogenesis of depression and be considered as a promising candidate for antidepressant treatment. This paper provides an overview of the structure and function of TRPV1 channel, with a focus on elucidating the potential mechanism of action of TRPV1 channel in depression, and explores its research trajectory and development prospects in the context of depression therapy.