ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

ObjectiveCerebrospinal fluid (CSF) plays a crucial role in maintaining the homeostasis of the central nervous system (CNS). CSF rapidly exchanges with interstitial fluid (ISF) via the glymphatic system within the brain parenchyma. CSF-ISF circulation and its associated mechanisms are often referred to as the brain lymphatic system. This system is connected directly to meningeal lymphatic vessels (mLVs), jointly performing the function of clearing metabolic waste from the CNS. Emerging evidence indicates that this system is closely associated with the onset and progression of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD). Importantly, abnormal CSF circulation is not only a downstream consequence of AD pathology, but also a risk factor. In AD, the dynamics of CSF flow within the CNS are diminished, immune dysregulation occurs, and this may increase the risk of AD by exacerbating the burden of amyloid β-protein (Aβ). In the mouse model of AD, impaired CSF flow compromises this clearance function, leading to cognitive deficits. Clinically, acupuncture at cognition-related acupoints is commonly used for the prevention and treatment of AD. However, whether its therapeutic effects are mediated through the modulation of CSF dynamics remains unclear. This study aimed to evaluate the impact of acupuncture on CSF flow and investigate its acupoint specificity. MethodsMice were randomly assigned to experimental groups for the different electroacupuncture groups with the following acupoints: Baihui point (GV 20), Ear point, Neiguan point (PC 6), and Tianshu point (ST 25). Wild-type mice on a C57BL/6J background were used as controls. Fluorescent tracer was injected into the cisterna magna to label CSF flow. Fluorescence imaging was employed to assess the distribution of CSF within the brain before and after acupuncture stimulation. ResultsFollowing tracer injection into the cisterna magna, fluorescence signals rapidly reached the cerebellum and medulla—the regions closest to the injection site. Fluorescence intensity was higher in ventral brain regions compared to dorsal regions, likely due to greater vascular density in ventral areas facilitating CSF-ISF exchange. Electroacupuncture at the GV 20 produced the most pronounced enhancement of CSF across the whole brain, while stimulation at the ST 25 primarily augmented flow within subcortical regions. In contrast, electroacupuncture at the Ear point or the PC 6 had no observable effect on CSF in mice. ConclusionElectroacupuncture promotes CSF flow into the brain parenchyma in an acupoint-specific manner, with GV 20 exhibiting the most pronounced enhancement of CSF dynamics. These findings suggest that acupuncture-mediated facilitation of CSF flow may represent a potential therapeutic strategy for preventing or delaying age-related cognitive decline.

ObjectiveCerebrospinal fluid (CSF) plays a crucial role in maintaining the homeostasis of the central nervous system (CNS). CSF rapidly exchanges with interstitial fluid (ISF) via the glymphatic system within the brain parenchyma. CSF-ISF circulation and its associated mechanisms are often referred to as the brain lymphatic system. This system is connected directly to meningeal lymphatic vessels (mLVs), jointly performing the function of clearing metabolic waste from the CNS. Emerging evidence indicates that this system is closely associated with the onset and progression of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD). Importantly, abnormal CSF circulation is not only a downstream consequence of AD pathology, but also a risk factor. In AD, the dynamics of CSF flow within the CNS are diminished, immune dysregulation occurs, and this may increase the risk of AD by exacerbating the burden of amyloid β-protein (Aβ). In the mouse model of AD, impaired CSF flow compromises this clearance function, leading to cognitive deficits. Clinically, acupuncture at cognition-related acupoints is commonly used for the prevention and treatment of AD. However, whether its therapeutic effects are mediated through the modulation of CSF dynamics remains unclear. This study aimed to evaluate the impact of acupuncture on CSF flow and investigate its acupoint specificity. MethodsMice were randomly assigned to experimental groups for the different electroacupuncture groups with the following acupoints: Baihui point (GV 20), Ear point, Neiguan point (PC 6), and Tianshu point (ST 25). Wild-type mice on a C57BL/6J background were used as controls. Fluorescent tracer was injected into the cisterna magna to label CSF flow. Fluorescence imaging was employed to assess the distribution of CSF within the brain before and after acupuncture stimulation. ResultsFollowing tracer injection into the cisterna magna, fluorescence signals rapidly reached the cerebellum and medulla—the regions closest to the injection site. Fluorescence intensity was higher in ventral brain regions compared to dorsal regions, likely due to greater vascular density in ventral areas facilitating CSF-ISF exchange. Electroacupuncture at the GV 20 produced the most pronounced enhancement of CSF across the whole brain, while stimulation at the ST 25 primarily augmented flow within subcortical regions. In contrast, electroacupuncture at the Ear point or the PC 6 had no observable effect on CSF in mice. ConclusionElectroacupuncture promotes CSF flow into the brain parenchyma in an acupoint-specific manner, with GV 20 exhibiting the most pronounced enhancement of CSF dynamics. These findings suggest that acupuncture-mediated facilitation of CSF flow may represent a potential therapeutic strategy for preventing or delaying age-related cognitive decline.

Aim Mouse model of myocardial hypertro-phy was established via intraperitoneal injection of iso-proterenol(ISO)in mice.This approach allows for an in-depth investigation into the pharmacological effects and mechanisms of action of emodin,offering novel in-sights and directions for the improvement of myocardial hypertrophy.Methods The mice were randomly di-vided into the following groups:control group(CON),emodin group(EMO),MAPK activator control group(EMO+Ani),model group(ISO),treatment group(ISO+EMO),and activator intervention group(ISO+EMO+Ani).After treatment with emodin and inter-vention with MAPK activator,the heart weight ratio and cardiac size of each group were observed.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in cardiac tissue,and kits were utilized to measure the levels of GSH,LDH,and MDA in the serum.Western blot was employed to detect the protein expression levels of inflammatory and oxidative factors,as well as p-p38,p-ERK,p38,and ERK in cardiac tis-sue.Results Emodin can significantly inhibit the production of myocardial inflammatory and oxidative factors induced by ISO,thereby effectively alleviating the degree of myocardial hypertrophy and fibrosis.Af-ter the p38/ERK signaling pathway was specifically ac-tivated by farnesol,the improvement effect of emodin on myocardial hypertrophy was weakened.Further comparison revealed that,compared with the myocardi-al hypertrophy pathological model group,the pathologi-cal protein expression levels in the farnesol-treated group showed no significant difference,and were even higher in some indicators.Conclusion Emodin can effectively inhibit the release of inflammatory factors and improve the state of oxidative stress by modulating the p38/ERK signaling pathway,thereby exerting an ameliorative effect on myocardial hypertrophy.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Objective:To investigate the value of habitat radiomic features based on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI in establishing a predictive model for cytokeratin 19 (CK19) expression in hepatocellular carcinoma (HCC) and to evaluate its role in prognostic risk stratification.Methods:This multicenter case-control study retrospectively enrolled 489 patients with pathologically confirmed HCC who underwent Gd-EOB-DTPA-enhanced MRI between June 2016 and June 2024. Among them, 346 patients from the First Affiliated Hospital of Soochow University were divided into a training cohort ( n=245) and an internal test cohort ( n=101) via stratified sampling at a 7∶3 ratio. And 143 patients from Nantong Third Hospital Affiliated to Nantong University served as an external validation cohort. The training cohort included 53 CK19-positive and 192 CK19-negative patients. The internal test cohort included 21 CK19-positive and 80 CK19-negative patients. The external validation cohort included 30 CK19-positive and 113 CK19-negative patients. Univariate logistic regression analysis was performed to identify potential factors associated with CK19 expression, and a clinical-radiologic model was constructed. The k-means clustering algorithm was applied to segment target HCC lesions into 3 subregions. Radiomic features were extracted and selected from these habitat subregions. Habitat radiomics models were constructed for the arterial phase (AP), portal venous phase, hepatobiliary phase (HBP), and combined phases (CP). Multivariate logistic regression analysis identified independent clinical and radiologic predictors of CK19 expression, and the optimal habitat model score was integrated to build a clinical-radiologic-habitat combined model. The area under the receiver operating characteristic curve (AUC) was used to evaluate model predictive performance. Recurrence-free survival (RFS) was analyzed using the Kaplan-Meier method and the differences in survival curves were compared with the log-rank test. Results:Univariate logistic regression analysis revealed that alpha-fetoprotein (AFP) ( OR=2.629, 95% CI 1.412-4.896, P=0.002), AP enhancement ( OR=3.636, 95% CI 1.642-8.052, P=0.001), AP peritumoral enhancement ( OR=2.219, 95% CI 1.084-4.542, P=0.029), and HBP peritumoral hypointensity ( OR=2.010, 95% CI 1.004-4.021, P=0.049) were potential factors associated with CK19 expression, which were incorporated into the clinical-radiologic model. In the internal and external validation cohorts, the AUC of the clinical-radiologic model was 0.690 (95% CI 0.590-0.778) and 0.650 (95% CI 0.565-0.727), respectively. The habitat radiomics model based on CP images demonstrated the highest performance. It achieved AUC of 0.729 (95% CI 0.622-0.836) and 0.725 (95% CI 0.607-0.842) in the internal and external validation cohorts, respectively. Multivariate analysis identified AFP ( OR=2.494, 95% CI 1.163-5.348, P=0.019), AP enhancement ( OR=5.230, 95% CI 1.868-14.643, P=0.002) and habitat radiomics model score ( OR=4.105, 95% CI 2.643-6.368, P<0.001) as independent predictors of CK19 positivity. Based on these factors, a combined clinical-radiologic-habitat combined model was established. The clinical-radiologic-habitat combined model achieved AUCs of 0.767 (95% CI 0.671-0.846) and 0.730 (95% CI 0.649-0.801) in the internal and external validation cohorts, respectively. Significant differences in RFS were observed between the CK19-positive group (25.1 month) and CK19-negative group (51.0 month) as predicted by the clinical-radiologic-habitat model ( χ2=4.17, P=0.041). Conclusion:The clinical-radiologic-habitat combined model based on Gd-EOB-DTPA-enhanced MRI habitat radiomics demonstrates good predictive performance for CK19 expression in HCC and offers valuable prognostic stratification for clinical practice.

Objective:To explore the value of the deep learning model based on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI in preoperatively predicting vessels completely encapsulating tumor clusters (VETC) in hepatocellular carcinoma (HCC).Methods:This study adopted a case-control design to retrospectively analyze 420 patients with HCC confirmed by postoperative pathology who underwent Gd-EOB-DTPA enhanced MRI between June 2016 and March 2023. A total of 420 patients were divided into a training set ( n=305) from the First Affiliated Hospital of Soochow University and an external validation set ( n=115) from Affiliated Nantong Hospital 3 of Nantong University. Based on postoperative pathological findings, patients were stratified into VETC-positive and VETC-negative groups. The training set comprised 161 VETC-positive cases and 144 VETC-negative cases, while the external validation set included 55 VETC-positive cases and 60 VETC-negative cases. Tumor regions of interest in arterial, portal venous, and hepatobiliary phases were manually delineated using ITK-SNAP software. Pre-trained Vgg19, Densenet121, and Vision Transformer (ViT) models were employed for transfer learning, extracting deep learning features from each image. Feature data were processed using FAE software, and 12 logistic regression models (arterial phase, portal venous phase, hepatobiliary phase, and combined three-phase models) were constructed to select the optimal deep learning model. Independent predictors in clinical characteristics were identified through univariate and multivariate logistic analyses to establish a clinical model for predicting VETC pattern. Subsequently, a clinical-deep learning fusion model was developed by integrating these clinical predictors with the optimal deep learning features. Model performance in predicting VETC-positive HCC was evaluated using receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). Results:In the external validation set, the area under the curve (AUC) of the Vgg19 model in the arterial phase, portal venous phase, hepatobiliary phase, and combined three-phase, respectively were 0.799,0.756,0.789,0.821, which were higher than those of Densenet121 (AUC: 0.544,0.581,0.544,0.583) and ViT (AUC: 0.740,0.752,0.785,0.767) model. The three-phase combined Vgg19 model achieved the highest AUC of 0.821 (95% CI 0.746-0.897). Multivariate logistic regression identified alpha-fetoprotein level ( OR=1.826,95% CI 1.069-3.120, P=0.028) and tumor diameter ( OR=1.329,95% CI 1.206-1.466, P<0.001) as independent predictors of VETC-positive HCC, forming the clinical model with an AUC of 0.789 (95% CI 0.703-0.859). The clinical-deep learning fusion model further achieved the AUC of 0.825 (95% CI 0.749-0.900). Calibration curves confirmed high concordance between predicted and actual probabilities for the three-phase Vgg19 model, while DCA revealed greater net clinical benefit for the combined Vgg19 and fusion models compared with the clinical model alone. Conclusions:The deep learning model based on Gd-EOB-DTPA enhanced MRI can be used to predict VETC of HCC preoperatively, among which the three-phase combined Vgg19 model and the clinical-deep learning model provide high predictive value.

Objective To analyze the association between lifestyle and the risk of type 2 diabetes(T2D)among adult residents.Methods The data was sourced from the Shanghai Suburban Adult Cohort and Biobank.A total of 42 096 adult residents who had not developed T2D were recruited from four districts of Shanghai(Songjiang,Jiading,Minhang,and Xuhui)between 2016 and 2019.The follow-up ended on Feb 28,2023.A structured questionnaire was used to collect information on six lifestyle-related items,including smoking,alcohol consumption,BMI,waist circumference(WC),physical activity,and diet.The unhealthy lifestyle scores(UHLS)were calculated by counting the number of all the unhealthy lifestyle items,with a range of 0-6.New-onset T2D events diagnosed by physicians were obtained through the medical information system.Cox proportional hazards regression model and restricted cubic spline model were utilized to evaluate the association between unhealthy lifestyles and the risk of T2D incidence.Results About 28.1%of the participants led 4-6 unhealthy lifestyles.A total of 1 752 new T2D cases were identified during 218 513.4 person-years of follow-up.Analysis of single unhealthy lifestyle showed that abnormal WC(HR=1.5,95%CI:1.4-1.7)and abnormal BMI(HR=1.3,95%CI:1.2-1.5)were associated with an increased risk of T2D.Compared with individuals with a UHLS of 0-1,those with a UHLS of 3 and 4-6 had 30%(95%CI:1.1-1.6)and 50%(95%CI:1.2-1.8)higher risks of T2D,respectively.Each additional unhealthy lifestyle was associated with a 10%increase in T2D incidence risk(HR=1.1,95%CI:1.1-1.2).Conclusion The risk of T2D in adult residents increases with the cumulative number of unhealthy lifestyles.Adult residents with abnormal WC or BMI,or have three or more unhealthy lifestyles accumulated,will increase the risk of new-onset T2D.

Acute respiratory distress syndrome(ARDS)is a common respiratory emergency,but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures.Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS,but the application of hydrogen has flammable and explosive safety concerns.Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance,thus improving ARDS in patients and animal models.Coral calcium hydrogenation(CCH)is a new solid molecular hydrogen carrier prepared from coral calcium(CC).Whether and how CCH affects acute lung injury in ARDS re-mains unstudied.In this study,we observed the therapeutic effect of CCH on lipopolysaccharide(LPS)induced acute lung injury in ARDS mice.The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable,demonstrating a significant improvement compared to the untreated ARDS model group.CCH treatment significantly reduced pulmonary hemorrhage and edema,and improved pulmonary function and local microcirculation in ARDS mice.CCH promoted mitochon-drial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2(Trx2),improved lung mitochondrial dysfunction induced by LPS,and reduced oxidative stress damage.The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

Objective:To investigate the value of habitat radiomic features based on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI in establishing a predictive model for cytokeratin 19 (CK19) expression in hepatocellular carcinoma (HCC) and to evaluate its role in prognostic risk stratification.Methods:This multicenter case-control study retrospectively enrolled 489 patients with pathologically confirmed HCC who underwent Gd-EOB-DTPA-enhanced MRI between June 2016 and June 2024. Among them, 346 patients from the First Affiliated Hospital of Soochow University were divided into a training cohort ( n=245) and an internal test cohort ( n=101) via stratified sampling at a 7∶3 ratio. And 143 patients from Nantong Third Hospital Affiliated to Nantong University served as an external validation cohort. The training cohort included 53 CK19-positive and 192 CK19-negative patients. The internal test cohort included 21 CK19-positive and 80 CK19-negative patients. The external validation cohort included 30 CK19-positive and 113 CK19-negative patients. Univariate logistic regression analysis was performed to identify potential factors associated with CK19 expression, and a clinical-radiologic model was constructed. The k-means clustering algorithm was applied to segment target HCC lesions into 3 subregions. Radiomic features were extracted and selected from these habitat subregions. Habitat radiomics models were constructed for the arterial phase (AP), portal venous phase, hepatobiliary phase (HBP), and combined phases (CP). Multivariate logistic regression analysis identified independent clinical and radiologic predictors of CK19 expression, and the optimal habitat model score was integrated to build a clinical-radiologic-habitat combined model. The area under the receiver operating characteristic curve (AUC) was used to evaluate model predictive performance. Recurrence-free survival (RFS) was analyzed using the Kaplan-Meier method and the differences in survival curves were compared with the log-rank test. Results:Univariate logistic regression analysis revealed that alpha-fetoprotein (AFP) ( OR=2.629, 95% CI 1.412-4.896, P=0.002), AP enhancement ( OR=3.636, 95% CI 1.642-8.052, P=0.001), AP peritumoral enhancement ( OR=2.219, 95% CI 1.084-4.542, P=0.029), and HBP peritumoral hypointensity ( OR=2.010, 95% CI 1.004-4.021, P=0.049) were potential factors associated with CK19 expression, which were incorporated into the clinical-radiologic model. In the internal and external validation cohorts, the AUC of the clinical-radiologic model was 0.690 (95% CI 0.590-0.778) and 0.650 (95% CI 0.565-0.727), respectively. The habitat radiomics model based on CP images demonstrated the highest performance. It achieved AUC of 0.729 (95% CI 0.622-0.836) and 0.725 (95% CI 0.607-0.842) in the internal and external validation cohorts, respectively. Multivariate analysis identified AFP ( OR=2.494, 95% CI 1.163-5.348, P=0.019), AP enhancement ( OR=5.230, 95% CI 1.868-14.643, P=0.002) and habitat radiomics model score ( OR=4.105, 95% CI 2.643-6.368, P<0.001) as independent predictors of CK19 positivity. Based on these factors, a combined clinical-radiologic-habitat combined model was established. The clinical-radiologic-habitat combined model achieved AUCs of 0.767 (95% CI 0.671-0.846) and 0.730 (95% CI 0.649-0.801) in the internal and external validation cohorts, respectively. Significant differences in RFS were observed between the CK19-positive group (25.1 month) and CK19-negative group (51.0 month) as predicted by the clinical-radiologic-habitat model ( χ2=4.17, P=0.041). Conclusion:The clinical-radiologic-habitat combined model based on Gd-EOB-DTPA-enhanced MRI habitat radiomics demonstrates good predictive performance for CK19 expression in HCC and offers valuable prognostic stratification for clinical practice.