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.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

BACKGROUND:Mitophagy is closely associated with the development of idiopathic pulmonary fibrosis,but its mechanism remains unclear.OBJECTIVE:To investigate the biological mechanism of mitophagy in idiopathic pulmonary fibrosis and provide ideas for the risk prediction of idiopathic pulmonary fibrosis and subtype differentiation.METHODS:The mitophagy-related genes in idiopathic pulmonary fibrosis were obtained through GEO and Reactome Pathway databases.The mitophagy-related characteristic genes in idiopathic pulmonary fibrosis were screened based on intergroup differences and random forest model.GO functional enrichment analysis and KEGG,Reactome with WIKI pathway enrichment analyses were performed by g:Profiler database.Mitophagy subtypes in idiopathic pulmonary fibrosis were distinguished by consensus clustering method and immune infiltration analysis was performed.The mitophagy-related key gene was screened.Finally,the predictive value of mitophagy-related key gene for the risk of idiopathic pulmonary fibrosis was quantified by alignment diagram and the correlation between mitophagy-related key gene and clinical characteristics of idiopathic pulmonary fibrosis was explored.RESULTS AND CONCLUSION:(1)A total of 13 genes related to mitophagy in idiopathic pulmonary fibrosis were identified and 5 characteristic genes were screened,containing PINK1,RPS27A,SRC,HIF1A,and CDH6.(2)GO analysis was mainly involved in ubiquitin protein ligase binding,and cellular response to hypoxia.Pathway enrichment analysis was mainly involved in PINK1-PRKN mediated mitophagy,NOTCH signaling pathway,signaling by EGFR and angiogenesis.(3)HIF1A had significant expression differences between subtypes,which might serve as a key gene for the differentiation of mitophagy subtypes of idiopathic pulmonary fibrosis.(4)Immune infiltration analysis suggested that myeloid-derived suppressor cell,neutrophil and type 1 T helper cell might have infiltration differences between subtypes,while HIF1A was positively correlated with multiple immune cells.(5)Alignment diagram suggested that the risk of idiopathic pulmonary fibrosis might be predicted by the expression level of HIF1A.(6)Clinical characteristics analysis indicated patients with high expression of HIF1A might have poorer lung function and more severe fibrosis.It is concluded that PINK1,RPS27A,SRC,HIF1A,and CDH6 may influence the development of idiopathic pulmonary fibrosis through mitophagy,in which HIF1A may serve as a key gene for risk prediction with clinical subtype differentiation and HIF1A is strongly associated with the lung function of patients.

Objective To explore the pharmacokinetic(PK)characteristics of desloratadine tablets and reference drugs in healthy subjects,and evaluate their bioequivalence and safety.Methods The random,open,two-period,cross-over pharmacokinetic study method was adopted,each subject received a single oral dose of desloratadine tablets test drug(T)or reference drug(R)for 5 mg.The concentrations of desloratadine and 3-hydroxy desloratadine in plasma were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS);and the PK parameters were calculated by WinNonlin 8.1 software to evaluate the bioequivalence.Results The main PK parameters of T and R of desloratadine were as follows:the fasting condition Cmax were respectively(3 809.82±1 016.54)and(3 642.36±777.07)pg·mL-1;AUC0-120h were respectively(5.75 ×104±5.03 ×104)and(5.51 × 104±4.00 × 104)pg·h·mL-1;AUC0-∞ were respectively(6.85× 104±1.03× 104)and(6.37 × 104±7.92 × 104)pg·h·mL-1.The fed condition Cmax were respectively(4 398.98±1 191.22)and(4 744.4±1 511.97)pg·mL-1;AUC0-120h were respectively(5.25 × 104±1.82 × 104)and(5.55 × 104±1.98 × 104)pg·h·mL-1;AUC0-∞ were respectively(5.37 × 104±1.86 × 104)and(5.68 × 104±2.04 × 104)pg·h·mL-1.The 90％confidence interval of Cmax,AUC0-t and AUC0-∞ of desloratadine were all within 80.00％～125.00％.Conclusion There was no significant difference in the main PK parameters between T tablets and R under fasting or high-fat postprandial conditions,and desloratadine tablets were bioequivalent,safe and well tolerated.

Objective:To investigate the application of the conjugate gradient (CG) algorithm to treatment plan optimization for intensity-modulated brachytherapy (IMBT).Methods:The general Monte Carlo software TOPAS was utilized to simulate the 192Ir source of IMBT, and the unit dose contribution matrix was calculated. An objective function was established using the weighted least squares method and was solved using the CG algorithm to achieve optimized IMBT treatment plans. The optimization was validated using five clinical cervical cancer cases under modulation width 60°. The dose distributions of IMBT treatment plans under 45°, 60°, 90°, 120°, and 180° modulation widths were compared using the Wilcoxon test to determine the optimal IMBT treatment plan for cervical cancer treatment. Results:The CG algorithm successfully optimized IMBT treatment plans under modulation width 60° for five cases within 22.2 s on average. On the premise of sufficient target dose coverage, the average D2 cm 3 values of the bladder and rectum in IMBT treatment plans were 3.66 and 1.97 Gy, respectively, representing reductions of 0.54 and 0.69 Gy compared to traditional brachytherapy plans. For the five modulation widths, the D90% values of all IMBT treatment plans reached 6 Gy, without statistically significant differences ( P > 0.05). The average D2 cm 3 values of the bladder in IMBT treatment plans were significantly lower than those in the traditional brachytherapy plans( P<0.05), with modulation width 60° associated with the greatest reduction of 0.61 Gy. In contrast, the average D2 cm 3 values of the rectum under 45°, 60°, and 90° modulation widths decreased by 0.63, 0.54, and 0.45 Gy, respectively, compared to traditional plans, with statistically significant differences( P<0.05). Conclusions:The CG method enables rapid achievement of optimized IMBT treatment plans that meet clinical requirements, and modulation width 60° contributes to valid dosimetric optimization. This study can serve as a guide for the clinical implementation of IMBT.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.