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 understand the individual dose monitoring of occupational external exposure for radiation workers in Wuhan City and analyze the dose change trend, and to provide a scientific basis for radiation protection management of radiation workers. Methods The data on the monitoring results of occupational external exposure of radiation workers in Wuhan City from 2017 to 2021 were collected through the National Personal Dose Registration System, and the individual dose levels of different years, different occupational categories, and different levels of hospitals were analyzed. Results A total of 9 134 radiation workers were investigated, with an average annual effective dose per capita of 0.20 mSv/a. The overall personal annual effective dose from 2017 to 2021 showed a decreasing trend (P<0.001). The per capita annual effective dose in medical applications was higher than that in industrial applications (0.22 mSv vs 0.14 mSv; P<0.001). Among medical applications, diagnostic radiologists had the highest average annual effective dose (0.27 mSv), and among industrial applications, industrial irradiators had the highest average annual effective dose (0.29 mSv). The proportion of personnel with personal annual effective doses exceeding 1 mSv was higher in interventional radiology and industrial nondestructive testing (4.90% and 1.90%). The annual effective dose per capita in Class I and unrated hospitals was higher (0.35 mSv). Conclusion The average annual effective dose of radiation workers in Wuhan City has decreased year by year and has not exceeded the national standard limit (20 mSv). Radiation protection management still needs to focus on personnel with personal annual effective doses exceeding 1mSv in interventional radiology and industrial nondestructive testing, and supervision over primary healthcare institutions and industrial radiation should be strengthened.

Objective:To investigate the influence of cytochrome P450 2A6 (CYP2A6) gene polymorphisms on liver function injury in patients with hyperthyroidism treated with methimazole.Methods:The study selected 90 patients with hyperthyroidism who were treated with methimazole in the Department of Thyroid Surgery at the First Affiliated Hospital of Zhengzhou University from Sept. 2023 to Aug. 2024 as the research subjects. Based on the occurrence of liver injury, they were divided into a liver injury group ( n=36) and a non-liver injury group (n=54). Peripheral blood DNA was extracted from the patients, and the CYP2A6 gene genotypes (rs8192725, rs8192720, and rs28399433) were detected using the polymerase chain reaction (PCR) amplification method. The association between CYP2A6 gene polymorphisms and liver injury induced by methimazole treatment in hyperthyroidism was analyzed. Results:The comparison of genotype distribution frequencies at the rs8192725 locus between the liver injury group and the non-liver injury group showed a statistically significant difference ( P<0.05). The AG and GG genotypes at the rs8192725 locus were protective factors against liver injury in patients with hyperthyroidism (AG vs. AA, OR: 0.21; 95% CI: 0.08-0.57; P<0.05; GG vs. AA, OR: 0.24; 95% CI: 0.06-0.89; P<0.05; AG+GG vs. AA, OR: 0.22; 95% CI: 0.09-0.54; P<0.05). The frequency of the G allele of rs8192725 in the liver injury group was significantly lower than that in the non-liver injury group (G vs. A, OR: 0.36; 95% CI: 0.19-0.70; P<0.05), indicating that it is a protective factor for liver injury in hyperthyroid patients receiving methimazole treatment. Conclusions:The CYP2A6 gene polymorphism at the rs8192725 locus is associated with the occurrence of liver injury in patients with hyperthyroidism treated with methimazole. The G allele may be a protective factor against liver injury in patients with hyperthyroidism, suggesting that individualized treatment plans can be developed based on the patient's genotype.

Objective To establish an animal model of hand,foot,and mouth disease(HFMD)in Syrian hamsters coinfected with coxsackievirus A6(CVA6)and coxsackievirus B1(CVB1).Methods 42 Syrian hamsters were divided into a CVA6 infection group,CVB1 infection group,CVA6 and CVB1 coinfection group and control group.A HFMD model was established by nasal instillation of virus solution and phosphate-buffered saline.Clinical and physiological indicators and detoxification status were monitored and recorded for 15 d,and animals were selected on day 7(D7)after infection for histopathology and viral antigen and nucleic acid testing.Results Hamsters in the single-infection and coinfection groups showed clinical symptoms similar to human HFMD.White blood cell,neutrophil,and lymphocyte result were characteristic of viral infection.Both viral nucleic acids were detected in throat swabs,feces,blood,and tissues and both viruses were isolated from fecal samples.Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues.Conclusions Nasal instillation of a CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters,replicate herpes infection similar to human HFMD,and cause pathological viral myocarditis and encephalitis damage.The result showed that the coinfection group was more seriously affected than the single-infection group,with worse clinical symptoms,increased viral replication,and obvious tissue pathological damage.This study provides a reference for further basic and clinical research into human enterovirus coinfection.

Objective To analyze the expression levels of matrix metalloproteinase-10(MMP-10)and Toll-like receptor 2(TLR2)in serum of patients underwent decompression surgery(DC)for severe traumatic brain injury(sTBI),and to explore their relationship with disease outcome.Methods From April 2021 to April 2024,sTBI patients(n=94)who received DC treatment in a single center were collected as the observation group.Another 90 healthy volunteers who underwent physical examinations at our hospital were selected as the control group.Six months after surgery,sTBI patients were assigned into the good group(n=53)and the adverse group(n=41)according to the Glasgow Outcome Scale(GOS).Data was collected from each group and their differences were compared.Enzyme linked immunosorbent assay(ELISA)was used to measure serum levels of MMP-10 and TLR2.Spearman method was used to analyze the correlation between MMP-10,TLR2 levels and disease outcomes.Logistic regression model used to analyze influencing factors of disease outcomes in sTBI patients after DC.The receiver operating characteristic(ROC)curve was applied to evaluate the predictive value of serum MMP-10 and TLR2 levels for disease outcome in sTBI patients after DC.Results Compared with the control group,the expression levels of serum MMP-10 and TLR2 were prominently higher in the observation group(P＜0.05).Compared with the good group,the proportions of sTBI patients with cerebral herniation,multiple brain contusions and lacerations,and serum levels of MMP-10 and TLR2 were significantly higher in the adverse group,while Glasgow Coma Scale(GCS)score was significantly lower(P＜0.05).Serum levels of MMP-10 and TLR2 in sTBI patients were positively correlated with poor prognosis after DC(P＜0.05).Elevated levels of serum MMP-10 and TLR2,and the increased proportions of patients with cerebral herniation and multiple brain contusions were risk factors affecting the disease outcome after DC in sTBI patients,while elevated GCS score was a protective factor(P＜0.05).The area under the curve(AUC)for predicting disease outcome in sTBI patients after DC using serum MMP-10 and TLR2 alone and in combination was 0.839(95％CI:0.749-0.907),0.847(95％CI:0.758-0.913)and 0.925(95％CI:0.852-0.969),respectively.The combined detection was superior to the individual detections(Zcombination-MMP-10=2.199,Zcombination-TLR2=2.377,both P＜0.05).Conclusion The expression levels of serum MMP-10 and TLR2 in sTBI patients are significantly elevated,and both are prominently correlated with disease outcome after DC.

Objective:To investigate the influence of cytochrome P450 2A6 (CYP2A6) gene polymorphisms on liver function injury in patients with hyperthyroidism treated with methimazole.Methods:The study selected 90 patients with hyperthyroidism who were treated with methimazole in the Department of Thyroid Surgery at the First Affiliated Hospital of Zhengzhou University from Sept. 2023 to Aug. 2024 as the research subjects. Based on the occurrence of liver injury, they were divided into a liver injury group ( n=36) and a non-liver injury group (n=54). Peripheral blood DNA was extracted from the patients, and the CYP2A6 gene genotypes (rs8192725, rs8192720, and rs28399433) were detected using the polymerase chain reaction (PCR) amplification method. The association between CYP2A6 gene polymorphisms and liver injury induced by methimazole treatment in hyperthyroidism was analyzed. Results:The comparison of genotype distribution frequencies at the rs8192725 locus between the liver injury group and the non-liver injury group showed a statistically significant difference ( P<0.05). The AG and GG genotypes at the rs8192725 locus were protective factors against liver injury in patients with hyperthyroidism (AG vs. AA, OR: 0.21; 95% CI: 0.08-0.57; P<0.05; GG vs. AA, OR: 0.24; 95% CI: 0.06-0.89; P<0.05; AG+GG vs. AA, OR: 0.22; 95% CI: 0.09-0.54; P<0.05). The frequency of the G allele of rs8192725 in the liver injury group was significantly lower than that in the non-liver injury group (G vs. A, OR: 0.36; 95% CI: 0.19-0.70; P<0.05), indicating that it is a protective factor for liver injury in hyperthyroid patients receiving methimazole treatment. Conclusions:The CYP2A6 gene polymorphism at the rs8192725 locus is associated with the occurrence of liver injury in patients with hyperthyroidism treated with methimazole. The G allele may be a protective factor against liver injury in patients with hyperthyroidism, suggesting that individualized treatment plans can be developed based on the patient's genotype.

Objective To analyze the expression levels of matrix metalloproteinase-10(MMP-10)and Toll-like receptor 2(TLR2)in serum of patients underwent decompression surgery(DC)for severe traumatic brain injury(sTBI),and to explore their relationship with disease outcome.Methods From April 2021 to April 2024,sTBI patients(n=94)who received DC treatment in a single center were collected as the observation group.Another 90 healthy volunteers who underwent physical examinations at our hospital were selected as the control group.Six months after surgery,sTBI patients were assigned into the good group(n=53)and the adverse group(n=41)according to the Glasgow Outcome Scale(GOS).Data was collected from each group and their differences were compared.Enzyme linked immunosorbent assay(ELISA)was used to measure serum levels of MMP-10 and TLR2.Spearman method was used to analyze the correlation between MMP-10,TLR2 levels and disease outcomes.Logistic regression model used to analyze influencing factors of disease outcomes in sTBI patients after DC.The receiver operating characteristic(ROC)curve was applied to evaluate the predictive value of serum MMP-10 and TLR2 levels for disease outcome in sTBI patients after DC.Results Compared with the control group,the expression levels of serum MMP-10 and TLR2 were prominently higher in the observation group(P＜0.05).Compared with the good group,the proportions of sTBI patients with cerebral herniation,multiple brain contusions and lacerations,and serum levels of MMP-10 and TLR2 were significantly higher in the adverse group,while Glasgow Coma Scale(GCS)score was significantly lower(P＜0.05).Serum levels of MMP-10 and TLR2 in sTBI patients were positively correlated with poor prognosis after DC(P＜0.05).Elevated levels of serum MMP-10 and TLR2,and the increased proportions of patients with cerebral herniation and multiple brain contusions were risk factors affecting the disease outcome after DC in sTBI patients,while elevated GCS score was a protective factor(P＜0.05).The area under the curve(AUC)for predicting disease outcome in sTBI patients after DC using serum MMP-10 and TLR2 alone and in combination was 0.839(95％CI:0.749-0.907),0.847(95％CI:0.758-0.913)and 0.925(95％CI:0.852-0.969),respectively.The combined detection was superior to the individual detections(Zcombination-MMP-10=2.199,Zcombination-TLR2=2.377,both P＜0.05).Conclusion The expression levels of serum MMP-10 and TLR2 in sTBI patients are significantly elevated,and both are prominently correlated with disease outcome after DC.

Objective:To establish the quality standard of the standard decoction of wine-processed Coptidis Rhizoma by studying the extraction rate, fingerprint and component quantitative analysis.Methods:ccording to the Technical Requirements for Quality Control and Standard Formulation of Chinese Medicine Formula Granules, 15 batches of the standard decoction of wine-processed Coptidis Rhizoma were prepared, and the paste rate was determined; HPLC fingerprints of 15 batches of standard decoction of wine-processed Coptidis Rhizoma were established, and evaluated by combining similarity evaluation, clustering analysis, principal component analysis and orthogonal partial least squares discriminant analysis; the contents of berberine, epiberberine, pamadine, and safranine in the samples of the 15 batches were determined and analyzed their transfer rates.Results:A total of 15 batches of standard decoction samples were calibrated with 11 common peaks, referring to the recognition of 8 components. The similarity between the samples and the control product was greater than 0.900; the clustering analysis could cluster the 15 batches of samples into 2 classes; the results of the principal component analysis showed that the cumulative variance contribution rate of the 3 principal component factors was 89.388%; the OPLS-DA screened out the 3 components of the quality difference; the 15 batches of samples out of the paste rate was 15.7% -20.8%, and the mass fractions of berberine, epiberberine, safranine, and palmatine were 18.47%-24.38%, 2.82%-3.49%, 5.08%-6.69%, and 4.84%-6.68%, respectively, with transfer rates of 41.7%-61.7%, 46.9%-68.7%, 39.8%-61.5%, and 43.8%-65.2%.Conclusion:The fingerprint and content determination method established in this study is accurate, stable, simple, and can be used for the quality control and evaluation of the standard decoction of wine-processed Coptidis Rhizoma.

Objective To establish an animal model of hand,foot,and mouth disease(HFMD)in Syrian hamsters coinfected with coxsackievirus A6(CVA6)and coxsackievirus B1(CVB1).Methods 42 Syrian hamsters were divided into a CVA6 infection group,CVB1 infection group,CVA6 and CVB1 coinfection group and control group.A HFMD model was established by nasal instillation of virus solution and phosphate-buffered saline.Clinical and physiological indicators and detoxification status were monitored and recorded for 15 d,and animals were selected on day 7(D7)after infection for histopathology and viral antigen and nucleic acid testing.Results Hamsters in the single-infection and coinfection groups showed clinical symptoms similar to human HFMD.White blood cell,neutrophil,and lymphocyte result were characteristic of viral infection.Both viral nucleic acids were detected in throat swabs,feces,blood,and tissues and both viruses were isolated from fecal samples.Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues.Conclusions Nasal instillation of a CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters,replicate herpes infection similar to human HFMD,and cause pathological viral myocarditis and encephalitis damage.The result showed that the coinfection group was more seriously affected than the single-infection group,with worse clinical symptoms,increased viral replication,and obvious tissue pathological damage.This study provides a reference for further basic and clinical research into human enterovirus coinfection.

Objective:To investigate the effects of oleuropein (OLE) on the migration, invasion, and chemotherapy sensitivity of cervical cancer cells by regulating the phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT) signaling pathway.Methods:SiHa cells were treated with 0-80 μ mol/L OLEs to detect cell survival rate and screen for the optimal drug concentration. SiHa cells were randomly separated into SiHa group, OLE low concentration (OLE-L) group, OLE medium concentration (OLE-M) group, OLE high concentration (OLE-H) group, and OLE-H+PI3K activator 740Y-P (OLE-H+740Y-P) group. CCK-8 method was applied to detect the proliferation activity of cells in each group. Transwell experiment was applied to detect the migration and invasion abilities of cells in each group. Flow cytometry was applied to detect the apoptosis rate of cells in each group. Western blot was used to detect the expression levels of PI3K-AKT signaling pathway related proteins, epithelial mesenchymal transition (EMT), and resistance related proteins such as epithelial cadherin, vimentin, N-cadherin, and P-glycoprotein (P-gp) of cells in each group.Results:OLEs with concentrations of 5, 10, and 20 μmol/L were selected for subsequent experiments. Compared with the SiHa group, the survival rate, numbers of clone formation, migration and invasion of cells, and the expression levels of p-PI3K/PI3K, p-AKT/AKT, Vimentin, N-cadherin and P-gp in the OLE-L, OLE-M, and OLE-H groups gradually decreased ( P<0.05), while the apoptosis rate and E-cadherin expression level increased ( P<0.05). Compared to that before cisplatin treatment, the apoptosis rate of SiHa cells increased after cisplatin treatment ( P<0.05). The addition of PI3K activator 740Y-P on the basis of high concentration OLE reversed the trend of changes in the above indicators ( P<0.05) . Conclusions:OLE can inhibit the migration and invasion of cervical cancer cells, and improve their chemotherapy sensitivity. Its mechanism of action may be related to the inhibition of the PI3K-AKT signaling pathway.