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 construct prostate cancer(PCa)prediction models based on machine learning algorithms, so as to improve the accuracy of early diagnosis of PCa. Methods A retrospective analysis was performed on the clinical data of 504 patients who underwent prostate biopsy at our hospital during Jan. 2020 and Nov. 2024. Patients' age, body mass index(BMI), history of hypertension, diabetes and smoking, total prostate-specific antigen(tPSA), free prostate-specific antigen(fPSA), f/tPSA, prostate volume(PV), neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio(NLR), Prostate Imaging Reporting and Data System(PI-RADS)score, digital rectal examination(DRE)results, and pathological findings were collected. The patients were divided into the training and testing sets at a ratio of 7:3. Ten early diagnosis prediction models of PCa were constructed using 10 supervised machine learning algorithms. Model performance was evaluated and validated using metrics including area under the receiver operating characteristic curve(AUC), accuracy, sensitivity, specificity, calibration curves, and decision curve analysis(DCA). SHAP analysis was used to interpret the models, and to clarify the importance of each feature and the basis for model decisions. Results All models showed good predictive value, with the gradient boosting machine(GBM)model performing the best(AUC=0.905, accuracy=84.1%, sensitivity=90.2%, specificity=80.0%). Calibration curves indicated good calibration and fitting of the GBM model, while DCA demonstrated favorable clinical net benefits. SHAP analysis identified the most significant features affecting PCa occurrence in descending order:tPSA, f/tPSA, PIRADS score, PV, age, and DRE. Conclusion The GBM model exhibits the optimal performance among the 10 models. The importance of features for predicting the occurrence of PCa, from the highest to the lowest, is as follows:tPSA, f/tPSA, PIRADS score, PV, age, and DRE.

BACKGROUND:Previous studies have demonstrated that acupuncture at the governor meridian has precise efficacy in the treatment of ischemic stroke and can improve cerebral ischemia-reperfusion injury by attenuating pyroptosis,but the upstream regulatory mechanisms are not yet fully clarified.OBJECTIVE:To observe the neuroprotective effect of electroacupuncture in model rats of cerebral ischemia-reperfusion injury.METHODS:Twenty-seven Sprague-Dawley rats were randomly divided into sham surgery,model,and electroacupuncture groups,with nine rats in each group.Modified suture method was used to establish cerebral ischemia-reperfusion model rats in the model and electroacupuncture groups.The electroacupuncture group was subjected to electroacupuncture at"Baihui,""Fengfu,"and"Dazhui"acupoints,20 minutes each,once a day,for 7 consecutive days.After treatment,neurological deficit scoring and pole test were performed to assess behavioral changes.Tri-phenyl tetrazolium chloride staining was used to assess cerebral infarction size in rats.Hematoxylin-eosin staining was performed to observe morphological changes in cerebral cortex tissue on the infarcted side of rats.Immunofluorescence analysis was used to determine Iba-1 and reactive oxygen species levels in cerebral cortex tissue on the infarcted side of rats,ELISA method was used for measuring interleukin-1β,interleukin-6 and tumor necrosis factor α levels in cerebral cortex tissue on the infarcted side of rats.Real-time fluorescence quantitative PCR and western blot were used to detect mRNA and protein expression levels of thioredoxin interaction protein,nod-like receptor associated protein 3(NLRP3),Caspase-1 and interleukin-1β in cerebral cortex tissue on the infarcted side of rats respectively,and the interaction between thioredoxin interaction protein and NLRP3 was analyzed by immunoprecipitation.RESULTS AND CONCLUSION:(1)Compared with the sham surgery group,rats in the model group showed an increase in neurological deficit score,pole test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining in the model group showed neuronal degeneration and necrosis,with fragmented and dissolved nuclei and cellular vacuoles.(2)Compared with the model group,rats in the electroacupuncture group showed a reduction in neurological deficit score,pole climbing test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining showed that the pathological damage of neurons in cerebral cortex tissue on the infarcted side of rats in the electroacupuncture group was significantly attenuated,with significantly reduced cell necrosis and vacuolation.(3)Immunoprecipitation assay showed an interaction between thioredoxin interaction proteins and NLRP3 in the cerebral cortical tissues on the infarcted side of rats in the model group.To conclude,electroacupuncture has a significant therapeutic effect against cerebral ischemia-reperfusion injury,possibly by inhibiting the reactive oxygen species/thioredoxin interaction protein/NLRP3 cell pyroptosis signaling pathway and activation of microglia to reduce the release of inflammatory factors.

Objective:To explore the independent factors influencing extraprostatic extension (EPE) after radical prostatectomy(RP) in patients with clinically localized prostate cancer by utilizing the Surveillance, Epidemiology, and End Results (SEER) database. A nomogram model was developed and externally validated.Methods:Clinical and pathological data of 20 916 clinically localized prostate cancer patients (T 1-2N 0M 0) who underwent RP between 2010 and 2021 were extracted from the SEER database. The mean age was (61.71±7.09) years old, and a total of 17 835 patients (85.3%) were married.There were 2 243 patients (10.7%) with prostate-specific antigen (PSA) <4 ng/ml, 14 831 patients (70.9%) with ≥4 and <10 ng/ml, and 2 965 patients (14.2%) with ≥10 and <20 ng/ml. There were 14 870 patients (71.1%) with clinical staging of stage T 1, and 6 046 patients (28.9%) with T 2. There were 48 patients (0.2%) with pathological staging of stage T 1, 15 794 (75.5%) with T 2, 5 001(23.9%) with T 3, and 73 (0.3%) with T 4 stage after radical surgery.The patients of SEER database were divided into training and internal validation groups in a 7∶3 ratio by using stratified sampling. Additionally, data were collected for 75 clinically localized prostate cancer patients who underwent RP at the Second Affiliated Hospital of Zhengzhou University from September 2019 to September 2024, serving as the external validation group.The mean age was(65.39±7.45) years old. Among them, 73 (97.3%) were married. There were 2 patients (2.7%) with PSA <4 ng/ml, 17 patients (22.7%) with ≥4 and <10 ng/ml, and 34 patients (45.3%) with ≥10 and <20 ng/ml. There were 47 patients (62.7%) with clinical staging of stage T 1, and 28 patients (37.3%) with T 2. There were 7 patients (9.3%) with pathological staging of stage T 1, 48 patients (64.0%)with T 2, 18 patients (24.0%) with T 3, and 2 patients (2.7%) with T 4 stage after radical surgery. All patients were categorized into organ-confined (OC) and EPE groups based on post-surgical pathology. Univariate and multivariate logistic regression analyses, with a stepwise backward selection, were performed on the training group to identify independent risk factors of EPE, which were used to construct a nomogram model. Model performance was assessed using receiver operating characteristic (ROC) curve area under the curve (AUC), calibration curves, and decision curve analysis (DCA) for the training group, internal validation group, and external validation group. Results:EPE was observed in 3 585 cases (24.5%), 1 489 cases (23.8%), and 20 cases (26.7%) in the training, internal validation, and external validation groups, respectively. Logistic regression analyses identified preoperative age ( OR=1.026, P<0.001), PSA levels (≥10 and <20 ng/ml: OR=1.790, P<0.001; ≥20 ng/ml: OR=2.683, P<0.001), tumor maximum diameter (10-20 mm: OR=2.051, P<0.001; >20 mm: OR=3.937, P<0.001), biopsy Gleason score (score 7: OR=1.911, P<0.001; score 8: OR=2.906, P<0.001; score 9: OR = 5.278, P<0.001; score 10: OR=4.421, P=0.003), number of positive biopsy cores (≥4 cores: OR=1.260, P<0.001), and their proportion of total cores ( OR=1.012, P<0.001) as independent predictors of EPE. The nomogram model demonstrated good predictive performance, with AUC of 0.741, 0.748, and 0.724 in the training, internal validation, and external validation groups, respectively. Calibration and DCA curves confirmed the model’s excellent stability and generalizability. Conclusions:Age, PSA levels, maximum tumor diameter, biopsy Gleason score, number of positive biopsy cores, and their proportion of total cores are independent predictors of EPE after RP in clinically localized prostate cancer. The constructed model effectively predicts the risk of EPE occurrence.

BACKGROUND:Previous studies have demonstrated that acupuncture at the governor meridian has precise efficacy in the treatment of ischemic stroke and can improve cerebral ischemia-reperfusion injury by attenuating pyroptosis,but the upstream regulatory mechanisms are not yet fully clarified.OBJECTIVE:To observe the neuroprotective effect of electroacupuncture in model rats of cerebral ischemia-reperfusion injury.METHODS:Twenty-seven Sprague-Dawley rats were randomly divided into sham surgery,model,and electroacupuncture groups,with nine rats in each group.Modified suture method was used to establish cerebral ischemia-reperfusion model rats in the model and electroacupuncture groups.The electroacupuncture group was subjected to electroacupuncture at"Baihui,""Fengfu,"and"Dazhui"acupoints,20 minutes each,once a day,for 7 consecutive days.After treatment,neurological deficit scoring and pole test were performed to assess behavioral changes.Tri-phenyl tetrazolium chloride staining was used to assess cerebral infarction size in rats.Hematoxylin-eosin staining was performed to observe morphological changes in cerebral cortex tissue on the infarcted side of rats.Immunofluorescence analysis was used to determine Iba-1 and reactive oxygen species levels in cerebral cortex tissue on the infarcted side of rats,ELISA method was used for measuring interleukin-1β,interleukin-6 and tumor necrosis factor α levels in cerebral cortex tissue on the infarcted side of rats.Real-time fluorescence quantitative PCR and western blot were used to detect mRNA and protein expression levels of thioredoxin interaction protein,nod-like receptor associated protein 3(NLRP3),Caspase-1 and interleukin-1β in cerebral cortex tissue on the infarcted side of rats respectively,and the interaction between thioredoxin interaction protein and NLRP3 was analyzed by immunoprecipitation.RESULTS AND CONCLUSION:(1)Compared with the sham surgery group,rats in the model group showed an increase in neurological deficit score,pole test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining in the model group showed neuronal degeneration and necrosis,with fragmented and dissolved nuclei and cellular vacuoles.(2)Compared with the model group,rats in the electroacupuncture group showed a reduction in neurological deficit score,pole climbing test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining showed that the pathological damage of neurons in cerebral cortex tissue on the infarcted side of rats in the electroacupuncture group was significantly attenuated,with significantly reduced cell necrosis and vacuolation.(3)Immunoprecipitation assay showed an interaction between thioredoxin interaction proteins and NLRP3 in the cerebral cortical tissues on the infarcted side of rats in the model group.To conclude,electroacupuncture has a significant therapeutic effect against cerebral ischemia-reperfusion injury,possibly by inhibiting the reactive oxygen species/thioredoxin interaction protein/NLRP3 cell pyroptosis signaling pathway and activation of microglia to reduce the release of inflammatory factors.

Objective To explore the impact of different moving patterns during the dip-coating process on thickness distributions of polymer heart valves.Methods Based on the volume of fluid(VOF)multiphase flow model,the Eulerian wall-film(EWF)model,and dynamic mesh technology,the dip-coating manufacturing process of polymer heart valves were numerically simulated.The effects of vertical,horizontal,and circular moving patterns on flow characteristics of the surface impregnation liquid and liquid film distributions under self-rotation conditions of the models were mainly studied.Subsequently,seven identical test points were set on each valve leaflet to collect thickness data,and the coefficient of variation(CV)was calculated to evaluate the uniformity of the liquid film thickness.Given that the vertical and horizontal patterns had fewer moving planes,limiting the optimization space,the circular pattern(45°)with richer moving planes was selected as the basis for optimization,and comparative analysis of numerical simulation was conducted.Results In the vertical pattern,the peak CV was 0.461 3;in the horizontal pattern,the CV was 0.060 8;and in the circular pattern,the CV at 30°,45° and 60° were 0.457 5,0.272 8,and 0.255 6,respectively.After optimization,the CV for the circular pattern(45°)decreased to 0.052 5,representing an 80.7％reduction compared to the pre-optimization value.Conclusions The moving patterns significantly affect the uniformity of dip-coating thickness distributions.The horizontal pattern demonstrates the best uniformity,while the vertical pattern shows the poorest uniformity.The CV for the circular pattern decreases as the angle increases,with its uniformity between that of the vertical and horizontal patterns.Optimization of moving pattern parameters based on simulation results has improved the uniformity of thickness distributions.

Objective To explore the impact of different moving patterns during the dip-coating process on thickness distributions of polymer heart valves.Methods Based on the volume of fluid(VOF)multiphase flow model,the Eulerian wall-film(EWF)model,and dynamic mesh technology,the dip-coating manufacturing process of polymer heart valves were numerically simulated.The effects of vertical,horizontal,and circular moving patterns on flow characteristics of the surface impregnation liquid and liquid film distributions under self-rotation conditions of the models were mainly studied.Subsequently,seven identical test points were set on each valve leaflet to collect thickness data,and the coefficient of variation(CV)was calculated to evaluate the uniformity of the liquid film thickness.Given that the vertical and horizontal patterns had fewer moving planes,limiting the optimization space,the circular pattern(45°)with richer moving planes was selected as the basis for optimization,and comparative analysis of numerical simulation was conducted.Results In the vertical pattern,the peak CV was 0.461 3;in the horizontal pattern,the CV was 0.060 8;and in the circular pattern,the CV at 30°,45° and 60° were 0.457 5,0.272 8,and 0.255 6,respectively.After optimization,the CV for the circular pattern(45°)decreased to 0.052 5,representing an 80.7％reduction compared to the pre-optimization value.Conclusions The moving patterns significantly affect the uniformity of dip-coating thickness distributions.The horizontal pattern demonstrates the best uniformity,while the vertical pattern shows the poorest uniformity.The CV for the circular pattern decreases as the angle increases,with its uniformity between that of the vertical and horizontal patterns.Optimization of moving pattern parameters based on simulation results has improved the uniformity of thickness distributions.

Objective To investigate the impact of eccentric placement for various types of artificial aortic valves on downstream flow dynamics.Methods A physiological pulsatile circulation simulation system was employed and particle image velocimetry(PIV)was utilized to analyze the downstream flow field variations for bioprosthetic and mechanical valves under two placement conditions:centralized placement(0 mm)and eccentric placement(1 mm).Hemodynamic parameters such as velocity,vorticity,and viscous shear stress were assessed to evaluate the flow field characteristics.Results By analyzing the flow field variations at four characteristic time points,namely,early systole,acceleration phase,peak systole,and deceleration phase,a significant difference in flow field distribution between bioprosthetic and mechanical valves was observed.The bioprosthetic valve exhibited a centrally symmetric jet with a higher flow velocity,whereas the mechanical valve displayed a three-jet structure with a lower central flow velocity.Under eccentric placement,the blood flow in the aortic sinus region was sluggish,with a reduction in average velocity,hindering the formation and maintenance of vortices.During the peak systolic phase,the maximum viscous shear stresses in the sinus region for the bioprosthetic and mechanical valves were 0.45 and 0.67 Pa,respectively,approaching the threshold for endothelial cell damage.Conclusions Eccentric placement of both mechanical and bioprosthetic valves resulted in reduced sinus blood flow velocity and diminished viscous shear stress,creating favorable conditions for thrombus formation.In clinical practice,careful attention should be given to the placement of valve replacement to prevent eccentric placement.

BACKGROUND:Facet joint osteoarthritis is acknowledged as a significant contributor to lower back pain in the geriatric population.The advent of an innovative spinal facet joint fusion device presents a therapeutic option for intervening during the initial stages of facet joint osteoarthritis,and significantly reduces the incidence of a series of complications caused by poor early conservative treatment and late surgical treatment.However,its effect on the biomechanics of the lumbar spine is unknown.OBJECTIVE:To investigate the biomechanical disparities between the novel lumbar zygapophyseal joint fusion device and traditional fusion devices.METHODS:A comprehensive three-dimensional finite element model of the L3-S1 lumbar spine was established and validated.Based on this intact model,three groups of surgical models were constructed:a bilateral pedicle screw fixation model,a bilateral novel facet joint fusion fixation model,and a bilateral facet screw fixation model,with the surgical segment designated as L4-5.Under a load of 500 N,a torque of 7.5 Nm was applied to all lumbar models to calculate the range of motion,displacement values,and intervertebral disc stress values at the L4-5 segment;stress values at the L3-4 and L5-S1 segments were also measured.RESULTS AND CONCLUSION:(1)Compared with the intact model,the range of motion at the L4-5 segment was reduced in all surgical models.(2)The novel device exhibited the smallest range of motion at the L4-5 segment under left and right rotational conditions;the greatest range of motion at the L4-5 segment under extension conditions;and a greater range of motion under other conditions than the bilateral pedicle screw fixation model.(3)The novel device demonstrated the smallest displacement values at the L4-5 segment under left and right rotational conditions;under other conditions,the displacement values at the L4-5 segment were greater than those in the bilateral pedicle screw fixation model.(4)In terms of stress distribution at the L4-5 segment,the novel device consistently exhibited the smallest values across all conditions.(5)For the L3-4 segment,the novel device showed the greatest stress values under extension and left and right rotational conditions,while under other conditions,the values were lower than those in the bilateral pedicle screw fixation model.(6)Compared with pedicle screw fixation,the novel device produced smaller stress values at the L5-S1 segment.(7)This study indicates that,compared with pedicle screw fixation,the novel device impacts the biomechanics of the lumbar spine by fusing the facet joints.It provides stability while preserving the range of motion at the surgical segment and reduces stress on the intervertebral discs of the surgical and adjacent segments,thereby potentially delaying disc degeneration.This suggests that the novel device can achieve biomechanical effects similar to those of pedicle screw fixation in theory.

Objective:To explore the independent factors influencing extraprostatic extension (EPE) after radical prostatectomy(RP) in patients with clinically localized prostate cancer by utilizing the Surveillance, Epidemiology, and End Results (SEER) database. A nomogram model was developed and externally validated.Methods:Clinical and pathological data of 20 916 clinically localized prostate cancer patients (T 1-2N 0M 0) who underwent RP between 2010 and 2021 were extracted from the SEER database. The mean age was (61.71±7.09) years old, and a total of 17 835 patients (85.3%) were married.There were 2 243 patients (10.7%) with prostate-specific antigen (PSA) <4 ng/ml, 14 831 patients (70.9%) with ≥4 and <10 ng/ml, and 2 965 patients (14.2%) with ≥10 and <20 ng/ml. There were 14 870 patients (71.1%) with clinical staging of stage T 1, and 6 046 patients (28.9%) with T 2. There were 48 patients (0.2%) with pathological staging of stage T 1, 15 794 (75.5%) with T 2, 5 001(23.9%) with T 3, and 73 (0.3%) with T 4 stage after radical surgery.The patients of SEER database were divided into training and internal validation groups in a 7∶3 ratio by using stratified sampling. Additionally, data were collected for 75 clinically localized prostate cancer patients who underwent RP at the Second Affiliated Hospital of Zhengzhou University from September 2019 to September 2024, serving as the external validation group.The mean age was(65.39±7.45) years old. Among them, 73 (97.3%) were married. There were 2 patients (2.7%) with PSA <4 ng/ml, 17 patients (22.7%) with ≥4 and <10 ng/ml, and 34 patients (45.3%) with ≥10 and <20 ng/ml. There were 47 patients (62.7%) with clinical staging of stage T 1, and 28 patients (37.3%) with T 2. There were 7 patients (9.3%) with pathological staging of stage T 1, 48 patients (64.0%)with T 2, 18 patients (24.0%) with T 3, and 2 patients (2.7%) with T 4 stage after radical surgery. All patients were categorized into organ-confined (OC) and EPE groups based on post-surgical pathology. Univariate and multivariate logistic regression analyses, with a stepwise backward selection, were performed on the training group to identify independent risk factors of EPE, which were used to construct a nomogram model. Model performance was assessed using receiver operating characteristic (ROC) curve area under the curve (AUC), calibration curves, and decision curve analysis (DCA) for the training group, internal validation group, and external validation group. Results:EPE was observed in 3 585 cases (24.5%), 1 489 cases (23.8%), and 20 cases (26.7%) in the training, internal validation, and external validation groups, respectively. Logistic regression analyses identified preoperative age ( OR=1.026, P<0.001), PSA levels (≥10 and <20 ng/ml: OR=1.790, P<0.001; ≥20 ng/ml: OR=2.683, P<0.001), tumor maximum diameter (10-20 mm: OR=2.051, P<0.001; >20 mm: OR=3.937, P<0.001), biopsy Gleason score (score 7: OR=1.911, P<0.001; score 8: OR=2.906, P<0.001; score 9: OR = 5.278, P<0.001; score 10: OR=4.421, P=0.003), number of positive biopsy cores (≥4 cores: OR=1.260, P<0.001), and their proportion of total cores ( OR=1.012, P<0.001) as independent predictors of EPE. The nomogram model demonstrated good predictive performance, with AUC of 0.741, 0.748, and 0.724 in the training, internal validation, and external validation groups, respectively. Calibration and DCA curves confirmed the model’s excellent stability and generalizability. Conclusions:Age, PSA levels, maximum tumor diameter, biopsy Gleason score, number of positive biopsy cores, and their proportion of total cores are independent predictors of EPE after RP in clinically localized prostate cancer. The constructed model effectively predicts the risk of EPE occurrence.