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.

Depression is a common mental disorder that falls under the category of "stagnation syndrome" in traditional Chinese medicine （TCM）. Its complex pathogenesis poses challenges for the development of novel therapeutic agents. Currently， clinically used antidepressants are often accompanied by significant side effects， and statistics show that about one-third of patients do not respond to these medications. TCM demonstrates advantages in the treatment of depression through multi-target， multi-pathway and multi-mechanistic approaches. Pinelliae Rhizoma， a phlegm-resolving herb， exhibits effects such as drying dampness and resolving phlegm， as well as eliminating stuffiness and reducing masses. The characteristics of harmonizing Yin and Yang and resolving stagnation in the middle energizer align precisely with the pathogenesis of depression syndrome， demonstrating therapeutic efficacy in affected patients. Literature studies have found that the active ingredients of Pinelliae Rhizoma， such as cavidine， baicalein， β-sitosterol， as well as Pinelliae Rhizoma herb pairs， such as Pinelliae Rhizoma-Magnoliae Officinalis Cortex， Pinelliae Rhizoma-husked sorghum， Pinelliae Rhizoma-Prunellae Spica， exhibit significant antidepressant effects. Furthermore， TCM formulas containing Pinelliae Rhizoma as the principal therapeutic agent， such as Banxia Xiexin Tang， Banxia Houpo Tang， and Wendan Tang， as well as formulas incorporating Pinelliae Rhizoma like compound Xiaochaihu Tang， Chaihu Jia Longgu Muli Tang， and Erchen Tang， have also demonstrated favorable antidepressant efficacy. The antidepressant mechanism of these agents may involve modulation of 5-hydroxytryptamine （5-HT） and dopamine （DA） levels， up-regulation of brain-derived neurotrophic factor （BDNF） expression， regulation of the hypothalamus-pituitary-adrenal （HPA） axis， reduction of oxidative stress， modulation of nuclear transcription factor-κB （NF-κB） signaling pathway， and inhibition of microglia-mediated inflammatory responses. This review summarized the antidepressant mechanisms and clinical applications of the active components， herb pairs， and TCM formulas containing Pinelliae Rhizoma， aiming to provide a reference for modern research on the use of Pinelliae Rhizoma in antidepressant therapy.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Aim To explore the compatibility and po-tential mechanism of effective components of Biejia-Ezhu against triple negative breast cancer(TNBC)and verify it by experiments.Methods Effective compo-nents and targets of Biejia-Ezhu were obtained by TC-MSP and Swiss Target Prediction.Disease targets of TNBC were obtained from OMMI and GeneCards data-bases.The PPI network was constructed using STRING database.GO and KEGG path enrichment analysis was performed using DAVID database.Cytoscape3.9.1 software was used to construct the"drug-component-target-disease"network,screen key targets and compo-nents for molecular docking,and further verify the com-patibility of key components and targets in vitro.Re-sults ① A total of 71 effective components were iden-tified in the Biejia-Ezhu drug pair.There were 146 drug targets associated with the disease.A total of 113 signaling pathways were identified by KEGG analysis.The 71 potential active components of Biejia-Ezhu mainly acted on key targets such as mTORC1,ULK1,TNF,EGFR,ESR1,STAT3,HIF1A,and PTGS2.Mo-lecular docking results showed that glycine and curcu-min were the key active components of Biejia-Ezhu,and both had strong docking activity against key target proteins mTORC1 and ULK1.②The results of in vitro experiment showed that glycine combined with curcu-min significantly inhibited the proliferation and clonal formation ability of TNBC cells(P＜0.05),up-regula-ted the expression of autophagy marker LC3 Ⅱ/Ⅰ,down-regulated the expression of EGFR,down-regula-ted the expression of pathway protein mTORC1,p-mTOR,p-ULK1,and promoted the expression of path-way protein ULK1(P＜0.05).Conclusion The key component of Biejia-Ezhu against triple-negative breast cancer is glycine-curcumin,the mechanism of which may be related to the regulation of the mTORC1/ULK1 signaling pathway to promote autophagy.

Aim To explore the compatibility and po-tential mechanism of effective components of Biejia-Ezhu against triple negative breast cancer(TNBC)and verify it by experiments.Methods Effective compo-nents and targets of Biejia-Ezhu were obtained by TC-MSP and Swiss Target Prediction.Disease targets of TNBC were obtained from OMMI and GeneCards data-bases.The PPI network was constructed using STRING database.GO and KEGG path enrichment analysis was performed using DAVID database.Cytoscape3.9.1 software was used to construct the"drug-component-target-disease"network,screen key targets and compo-nents for molecular docking,and further verify the com-patibility of key components and targets in vitro.Re-sults ① A total of 71 effective components were iden-tified in the Biejia-Ezhu drug pair.There were 146 drug targets associated with the disease.A total of 113 signaling pathways were identified by KEGG analysis.The 71 potential active components of Biejia-Ezhu mainly acted on key targets such as mTORC1,ULK1,TNF,EGFR,ESR1,STAT3,HIF1A,and PTGS2.Mo-lecular docking results showed that glycine and curcu-min were the key active components of Biejia-Ezhu,and both had strong docking activity against key target proteins mTORC1 and ULK1.②The results of in vitro experiment showed that glycine combined with curcu-min significantly inhibited the proliferation and clonal formation ability of TNBC cells(P＜0.05),up-regula-ted the expression of autophagy marker LC3 Ⅱ/Ⅰ,down-regulated the expression of EGFR,down-regula-ted the expression of pathway protein mTORC1,p-mTOR,p-ULK1,and promoted the expression of path-way protein ULK1(P＜0.05).Conclusion The key component of Biejia-Ezhu against triple-negative breast cancer is glycine-curcumin,the mechanism of which may be related to the regulation of the mTORC1/ULK1 signaling pathway to promote autophagy.

OBJECTIVE To analyze a strain of multidrug-resistant Pseudomonas fulva by whole genome sequencing,investigate the genomic characteristics and analyze the significance in phyletic evolution.METHODS A strain of P.fulva,NY4814,was isolated from the Chinese PLA General Hospital in 2014.The genome sequence data of the strain were obtained after the purification,preservation and whole genome sequencing.The specie of the strain was identified by comparing with average nucleotide identity(ANI);the minimum inhibitory concentra-tions(MIC)of the strains were determined by VITEK2 system.All of the data regarding to the genomic se-quences of P.fulva were downloaded from RefSeq database of National Center of Biotechnology Information(NCBI)to construct the phylogenetic tree.RESULTS The P.fulva NY4814 was resistant to carbapenems and quinolones.The chromosome carried a newly discovered Tn7675 unit transposon,which mediated resistance to aminoglycosides and chloramphenicol.Simultaneously,the plasmid pNY4814-IMP drove the wide dissemination of the blaIMP resistance gene across Pseudomonas species via a highly conserved conjugative and transfer mechanism,and the Tn6485i unit transposon carried by the chromosome mediated the resistance to β-lactams.CONCLUSIONS As one of the potential carriers for the transmission of carbapenems resistance genes and other types of drug re-sistance genes,the P.fulva leads to the infection as a seldom opportunistic pathogen.The genetic structure of NY4814 and its association with genetic evolution of the species are observed in the study,which intensify the un-derstanding of the species and provide theoretical bases for prevention and monitoring of bacterial infections.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Objective To explore the feasibility and precautions of small incision bile duct stone removal in primary hospitals in extremely high-altitude areas.Methods The experience of small incision biliary exploration and cholecystectomy under general anesthesia at primary hospitals during the author's medical aid to Xizang in the high-altitude areas of northern Xizang was summarized(from June 2022 to December 2022).Results A total of 11 cases of small incision common bile duct stone removal were completed.Abdominal drainage was performed in all patients,including 6 cases with T-shaped tubes and 5 cases with primary closure of the common bile duct.The patients recovered well after surgery and was discharged.Conclusion In extreme high-altitude areas,under the guidance of medical aid doctors,it is completely feasible for primary hospitals to carry out small incision bile duct stone removal by selecting appropriate cases,training surgical skills,and performing detailed preoperative preparation.

Objective To investigate the diarrhea after minilaparotomy cholecystectomy among Tibetan residents in extremely high-altitude areas.Methods A retrospective analysis was conducted on the clinical data of 71 patients who underwent small incision cholecystectomy at the County People's Hospital during the period of medical aid(from June 2022 to December 2022).There were 38 patients(53.52%)with postoperative diarrhea and 33 patients(46.48%)without diarrhea.Results The duration of diarrhea was less than 1 week in 8 patients,ranged from 1 week to 3 months in 21 patients,and lasted for more than 3 months in 9 patients.There were significant differences between the two groups in terms of age(P<0.000 1),body mass index(P<0.000 1),proportions of patients with liver cirrhosis(P=0.012 9),history of acute cholecystitis(P=0.002 1),history of coronary heart disease(P=0.040 7),and presence of tenderness in the right upper abdomen during admission(P<0.000 1),white blood cell count(P=0.007 0),alanine aminotransferase(P=0.047 3),gallbladder diameter(P=0.003 4),gallbladder wall thickness(P=0.000 4),surgical duration(P=0.004 7),postoperative antibiotic use(P=0.000 6),postoperative hospital stay(P=0.000 2),and immediate resumption of butter tea(P<0.000 1).Age and immediate resumption of butter tea after surgery were independent risk factors for diarrhea after minilaparotomy cholecystectomy.Conclusion There is a higher incidence of diarrhea following small incision cholecystectomy in the residents of extremely high-altitude areas,which is associated with various factors such as the environment and lifestyle of the region.It is essential to enhance health education on gallstone and cultivate good personal health habits.Clinicians should conduct a detailed preoperative assessment.Patients should avoid drinking butter tea during perioperative period to avoid postoperative diarrhea.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.