ObjectiveTo construct a machine learning model combining two-dimensional shear wave elastography （2D-SWE） and serological markers， and to investigate its clinical value in differentiating primary biliary cholangitis （PBC） from overlap syndrome （OS）. MethodsA total of 199 patients with pathologically confirmed PBC or OS in Nantong Third People’s Hospital from January 2021 to December 2025 were retrospectively enrolled， with 125 patients in the PBC group and 74 in the OS group. The patients were randomly divided into a training set with 139 patients and a test set with 60 patients at a ratio of 7∶3. Related data were collected， including serological markers， conventional two-dimensional ultrasound parameters， and 2D-SWE parameters （including velocity of shear wave ［VS］ and liver fibrosis index ［LFI］）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The univariate and multivariate Logistic regression analyses were used to identify independent predictive factors， which were then incorporated into six machine learning models， and 5-fold cross-validation was used for optimization of parameters. The indicators including the area under the receiver operating characteristic curve （AUC） were compared in the test set to determine the best model， and the SHapley additive exPlanations （SHAP） analysis was used for model interpretation. ResultsFemale patients accounted for 87.8% in the OS group and 79.2% in the PBC group. Compared with the PBC group， the OS group had significantly higher age， VS， LFI， splenic area， aspartate aminotransferase， total bilirubin， prothrombin time， immunoglobulin G （IgG）， and immunoglobulin M （Z=-2.883， -6.524， -4.000， -3.061， -2.194， -2.372， -4.079， -6.964， and -2.709， all P<0.05） and a significantly lower platelet count （Z=4.098， P<0.001）， and there were also significant differences between the two groups in the proportion of patients with positive anti-nuclear antibody， fibrosis stage， and inflammation grade （χ²=3.458， 63.198， and 101.038， all P<0.05）. Variables without multicollinearity were included in the regression analysis， and the multivariate Logistic regression analysis showed that VS （odds ratio ［OR］=4.503， 95% confidence interval ［CI］： 1.698 — 11.943， P=0.003）， LFI （OR=1.813， 95%CI： 1.050 — 3.132， P=0.033）， and IgG （OR=1.121， 95%CI： 1.026 — 1.226， P=0.012） were independent predictive factors for differentiating PBC from OS. Six machine learning models were constructed based on these variables， among which the logistic regression model showed the best predictive performance in the test set， with an AUC of 0.881 （95%CI： 0.788 — 0.974）， a sensitivity of 0.731， and a specificity of 0.794. The SHAP analysis showed that IgG contributed the most to model prediction. ConclusionThe noninvasive multimodal machine learning model combining 2D-SWE parameters （VS， LFI） and serum IgG can effectively differentiate PBC from OS， providing a reference for clinical decision-making regarding the need for liver biopsy.

Objective:To investigate the targets and mechanisms of cycloastragenol in ameliorating azithromycin-induced drug-induced liver injury(DILI)based on network pharmacology and in vitro experiment validation.Methods:Potential targets of cycloastragenol and DILI were predicted using databases.The common and key targets were screened and subjected to GO and KEGG enrichment analyses,as well as molecular docking validation.Primary hepatocytes from C57BL/6 mice were isolated.The optimal concentration and time for azithromycin-induced DILI in mouse primary hepatocytes were determined using CCK8 and ROS assays.The expression of genes and proteins such as NF-κB p65,p-NF-κB p65,AMPKα,and p-AMPKα was assessed using RT-qPCR and Western blot to evaluate the intervention effect of cycloastragenol(10-50 μmol/L).Results:Network pharmacology analysis identified 10 key genes related to cycloastragenol's improvement of DILI,including heat shock protein 90AA1(HSP90AA1),matrix metalloproteinase 2(MMP2),etc.GO enrichment analysis suggested that cycloastragenol primarily regulates biological processes such as membrane potential and chemical synaptic transmission,and affects cellular components such as neuronal cell bodies and distal axons,and related kinase activities.KEGG enrichment analysis showed that it mainly exerts intervention effects through neuro-signaling pathways and IL-17 signaling pathways.Molecular docking demonstrated strong binding of cycloastragenol to HSP90AA1,MMP2,NF-κB p65,AMPKα,nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase 1(HO-1),and NAD(P)H:quinone oxidoreductase 1(NQO1),with a binding energy≤-5.0 kcal/mol for Nrf2.In vitro experiments showed that azithromycin(50 μmol/L,12 h)significantly reduced hepatocyte viability and increased ROS levels(P＜0.01).Different concentrations of cycloastragenol significantly improved the activity of mouse primary hepatocytes,reduced the generation of intracellular ROS,downregulated the phosphorylation level of NF-κB p65,and upregulated the mRNA and protein levels of AMPKα,Nrf2,HO-1,NQO1(P＜0.05).Conclusions:Cycloastragenol may alleviate azithromycin-induced hepatocyte oxidative stress and inflammation by inhibiting NF-κB phosphorylation and activating the AMPK/Nrf2/HO-1/NQO1 pathway,with its mechanism likely closely linked to targeting Nrf2.However,the complex mechanisms of DILI may involve additional unverified pathways.Therefore,further studies are necessary to validate the efficacy and safety of cycloastragenol in animal models.

Objective To investigate the expression of leukocyte cell-derived chemotaxin 2(LECT2)and complement C3 in the serum of patients with autoimmune hepatitis(AIH),and their correlation with liver function grading and prognosis.Methods A total of 109 AIH patients admitted to our hospital from January 2022 to February 2024 were included as the observation group.According to the disease activity upon admission,they were grouped into the active group(59 cases)and the remission group(50 cases).According to the Child-Pugh grading,they were assigned into the grade A group(47 cases),the grade B group(40 cases),and the grade C group(22 cases).According to the prognosis,they were assigned into a poor prognosis group(35 cases)and a good prognosis group(74 cases),with 110 healthy volunteers who underwent physical checkup in our hospital as the control group.Enzyme linked immunosorbent assay(ELISA)was applied to measure serum LECT2 level.Immunoturbidimetry was applied to detect serum complement C3 level.The correlation between LECT2,complement C3 and clinical indexes was analyzed by Pearson correlation analysis.Spearman correlation analysis was applied to analyze the relationship between serum LECT2,complement C3,and Child-Pugh grading.Receiver operating characteristic(ROC)curves were established to evaluate the predictive value of LECT2 and complement C3 levels for poor prognosis in AIH patients.Results The serum level of LECT2 in the observation group was higher than that in the control group,and the level of complement C3 was lower than that in the control group(P＜0.05).The expression level of ELECT2 in the grade C group was prominently higher than that in the grade B group and grade A group,while the expression level of complement C3 was prominently lower than that in the grade B group and grade A group(P＜0.05).The level of serum LECT2 in poor prognosis group was higher than that in good prognosis group,and the level of serum complement C3 was lower than that in good prognosis group(P＜0.05).Pearson correlation analysis showed that LECT2 was positively correlated with IgG,IL-6,TNF-α and Th17/Treg,and negatively correlated with TGF-β,while complement C3 was negatively correlated(all P＜0.05);Spearman correlation analysis showed that LECT2 level was positively correlated with Child-Pugh grading,while complement C3 level was negatively correlated with Child-Pugh grading(rs=0.803,-0.875,both P＜0.05).ROC curve reveled that the AUC of serum LECT2 and complement C3 levels in predicting poor prognosis of AIH patients was 0.802 and 0.805,respectively,the AUC of their combined detection was 0.905,which was higher than that of single indicator detection(P＜0.05).Conclusion Serum LECT2 level is elevated and complement C3 level is reduced in AIH patients,and they are correlated with liver function grading and disease severity.The combined detection of the two can serve as serological indicators for evaluating liver function and predicting prognosis.

Objective To investigate the expression of leukocyte cell-derived chemotaxin 2(LECT2)and complement C3 in the serum of patients with autoimmune hepatitis(AIH),and their correlation with liver function grading and prognosis.Methods A total of 109 AIH patients admitted to our hospital from January 2022 to February 2024 were included as the observation group.According to the disease activity upon admission,they were grouped into the active group(59 cases)and the remission group(50 cases).According to the Child-Pugh grading,they were assigned into the grade A group(47 cases),the grade B group(40 cases),and the grade C group(22 cases).According to the prognosis,they were assigned into a poor prognosis group(35 cases)and a good prognosis group(74 cases),with 110 healthy volunteers who underwent physical checkup in our hospital as the control group.Enzyme linked immunosorbent assay(ELISA)was applied to measure serum LECT2 level.Immunoturbidimetry was applied to detect serum complement C3 level.The correlation between LECT2,complement C3 and clinical indexes was analyzed by Pearson correlation analysis.Spearman correlation analysis was applied to analyze the relationship between serum LECT2,complement C3,and Child-Pugh grading.Receiver operating characteristic(ROC)curves were established to evaluate the predictive value of LECT2 and complement C3 levels for poor prognosis in AIH patients.Results The serum level of LECT2 in the observation group was higher than that in the control group,and the level of complement C3 was lower than that in the control group(P＜0.05).The expression level of ELECT2 in the grade C group was prominently higher than that in the grade B group and grade A group,while the expression level of complement C3 was prominently lower than that in the grade B group and grade A group(P＜0.05).The level of serum LECT2 in poor prognosis group was higher than that in good prognosis group,and the level of serum complement C3 was lower than that in good prognosis group(P＜0.05).Pearson correlation analysis showed that LECT2 was positively correlated with IgG,IL-6,TNF-α and Th17/Treg,and negatively correlated with TGF-β,while complement C3 was negatively correlated(all P＜0.05);Spearman correlation analysis showed that LECT2 level was positively correlated with Child-Pugh grading,while complement C3 level was negatively correlated with Child-Pugh grading(rs=0.803,-0.875,both P＜0.05).ROC curve reveled that the AUC of serum LECT2 and complement C3 levels in predicting poor prognosis of AIH patients was 0.802 and 0.805,respectively,the AUC of their combined detection was 0.905,which was higher than that of single indicator detection(P＜0.05).Conclusion Serum LECT2 level is elevated and complement C3 level is reduced in AIH patients,and they are correlated with liver function grading and disease severity.The combined detection of the two can serve as serological indicators for evaluating liver function and predicting prognosis.

Objective:To investigate the targets and mechanisms of cycloastragenol in ameliorating azithromycin-induced drug-induced liver injury(DILI)based on network pharmacology and in vitro experiment validation.Methods:Potential targets of cycloastragenol and DILI were predicted using databases.The common and key targets were screened and subjected to GO and KEGG enrichment analyses,as well as molecular docking validation.Primary hepatocytes from C57BL/6 mice were isolated.The optimal concentration and time for azithromycin-induced DILI in mouse primary hepatocytes were determined using CCK8 and ROS assays.The expression of genes and proteins such as NF-κB p65,p-NF-κB p65,AMPKα,and p-AMPKα was assessed using RT-qPCR and Western blot to evaluate the intervention effect of cycloastragenol(10-50 μmol/L).Results:Network pharmacology analysis identified 10 key genes related to cycloastragenol's improvement of DILI,including heat shock protein 90AA1(HSP90AA1),matrix metalloproteinase 2(MMP2),etc.GO enrichment analysis suggested that cycloastragenol primarily regulates biological processes such as membrane potential and chemical synaptic transmission,and affects cellular components such as neuronal cell bodies and distal axons,and related kinase activities.KEGG enrichment analysis showed that it mainly exerts intervention effects through neuro-signaling pathways and IL-17 signaling pathways.Molecular docking demonstrated strong binding of cycloastragenol to HSP90AA1,MMP2,NF-κB p65,AMPKα,nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase 1(HO-1),and NAD(P)H:quinone oxidoreductase 1(NQO1),with a binding energy≤-5.0 kcal/mol for Nrf2.In vitro experiments showed that azithromycin(50 μmol/L,12 h)significantly reduced hepatocyte viability and increased ROS levels(P＜0.01).Different concentrations of cycloastragenol significantly improved the activity of mouse primary hepatocytes,reduced the generation of intracellular ROS,downregulated the phosphorylation level of NF-κB p65,and upregulated the mRNA and protein levels of AMPKα,Nrf2,HO-1,NQO1(P＜0.05).Conclusions:Cycloastragenol may alleviate azithromycin-induced hepatocyte oxidative stress and inflammation by inhibiting NF-κB phosphorylation and activating the AMPK/Nrf2/HO-1/NQO1 pathway,with its mechanism likely closely linked to targeting Nrf2.However,the complex mechanisms of DILI may involve additional unverified pathways.Therefore,further studies are necessary to validate the efficacy and safety of cycloastragenol in animal models.

Background/Aims: The shortage of donor liver hinders the development of liver transplantation. This study aimed to clarify the poor outcomes of functionally marginal liver grafts (FMLs) and provide evidence for the improvement of ischemia-free liver transplantation (IFLT) after FML transplantation. Methods: Propensity score matching was used to control for confounding factors. The outcomes of the control group and FML group were compared to demonstrate the negative impact of FMLs on liver transplantation patients. We compared the clinical improvements of the different surgical types. To elucidate the underlying mechanism, we conducted bioinformatic analysis based on transcriptome and single-cell profiles. Results: FMLs had a significantly greater hazard ratio (HR: 1.969, P=0.018) than did other marginal livers. A worse 90-day survival (Mortality: 12.3% vs. 5.0%, P=0.007) was observed in patients who underwent FML transplantation. Patients who received FMLs had a significant improvement in overall survival after IFLT (Mortality: 10.4% vs 31.3%, P=0.006). Pyroptosis and inflammation were inhibited in patients who underwent IFLT. The infiltration of natural killer cells was lower in liver grafts from these patients. Bulk transcriptome profiles revealed a positive relationship between IL-32 and Caspase 1 (R=0.73, P=0.01) and between IL-32 and Gasdermin D (R=0.84, P=0.0012). Conclusions FML is a more important negative prognostic parameter than other marginal liver parameters. IFLT might ameliorate liver injury in FMLs by inhibiting the infiltration of NK cells, consequently leading to the abortion of IL-32, which drives pyroptosis in monocytes and macrophages.

Objective: To explore the effect of reducing complication in branched spongiosum repair for hypospadias Duckett surgery. Methods: Retrospective analysis was performed for the clinical data of 140 surgical infants with hypospadias Duckett surgery from January 2016 to April 2018. According to different covering materials on newly formed urethra, the experimental group (68 cases) cut dysplasia, branched spongiosum and lateral Buck′s fascia from tunica albuginea to coronary groove and then sutured over newly formed urethra, and the control group (72 cases) used Dartos fascia or subcutaneous fascia. The operative age, penile curvature, length of urethral defect, operation time, added value of coronary groove before and after operation, maximum urinary flow rate and complication rate of postoperative follow-up were compared between the two groups, and the therapeutic effect was analyzed. Results: There was no statistically significant difference between two groups in operating time[(135±49)min vs.(135±45)min, P=0.580] and the value added of coronary sulcus[(0.1±0.2)cm vs.(0.1±0.1)cm, P=0.167]. In experimental group, there were 8 cases of urethra percutaneous fistula (11.8%) (coronary groove fistula in 3 cases, 4.4%)and 6 cases of urethral stenosis (8.8%) without urethral dehiscence. In control group, there were 18 cases of urethra percutaneous fistula (25.0%)(coronary groove fistula in 11 cases, 15.3%), 10 cases of urethral stenosis (13.9%), and 2 cases of urethral dehiscence (2.8%). The incidence of postoperative urinary fistula and total complications in experimental group was lower than that in the control group, and the difference was statistically significant (P<0.05), while the incidence of urethral stenosis was not statistically different between two groups (P>0.05). The maximum urine flow rate of experimental group at 6 months after surgery was significantly higher than control group[(9.5±3.8)ml/s vs.(6.8±2.8)ml/s], and the difference was statistically significant (P<0.001). Conclusions Urethral cavernosum reconstruction can significantly reduce the incidence of postoperative coronary groove fistula of hypospadias Duckett surgery and improve the postoperative urine flow rate.

The drug-target protein interaction prediction can be used for the discovery of new drug effects. Recent studies often focus on the prediction of an independent matrix filling algorithm, which apply a single algorithm to predict the drug-target protein interaction. The single-model matrix-filling algorithms have low accuracy, so it is difficult to obtain satisfactory results in the prediction of drug-target protein interaction. AdaBoost algorithm is a strong multiple classifier combination framework, which is proved by the past researches in classification applications. The drug-target interaction prediction is a matrix filling problem. Therefore, we need to adjust the matrix filling problem to a classification problem before predicting the interaction among drug-target protein. We make full use of the AdaBoost algorithm framework to integrate several weak classifiers to improve performance and make accurate prediction of drug-target protein interaction. Experimental results based on the metric datasets show that our algorithm outperforms the other state-of-the-art approaches and classical methods in accuracy. Our algorithm can overcome the limitations of the single algorithm based on machine learning method, exploit the hidden factors better and improve the accuracy of prediction effectively.

Objective To evaluate the short-term outcome of the Kelly procedure for bladder exstrophy-epispadias complex.Methods Kelly procedure was performed in 5 cases from December 2015 in our institute. Retrospective analysis was done including the surgery and follow up.Results Two bladder exstrophy boys had histories of primary bladder closure without bladder neck reconstruction during the neonatal period. Another three epispadias boys had sever urethral defects with full incontinence. All cases undertook Kelly procedure and were followed up for 7.8 months (2-12 months). No severe complications such as glanular necrosis, urethral stricture and urethrocutaneous fistula was observed. Four cases were fully continent and one epispadias case had stress incontinence.Conclusions Kelly procedure produced satisfactory urinary continence and phallic cosmetics in bladder exstrophy-epispadias complex in children. Proper identification of the pudendal neurovascular bundle and repair of the external sphincter by levatorplasty help improve the outcome.