Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

Objective To establish an animal model of osteoporosis combined with liver cirrhosis and conduct preliminary investigation into the effect of liver cirrhosis on bone loss in mice and the underlying mechanisms.Methods The experimental animals were 25 6-week-old female C57BL/6 mice with a body weight of approximately 20-22 g.A comorbidity model of liver cirrhosis and osteoporosis was established in the mice by ovariectomy combined with carbon tetrachloride(CCl4)induction.The mice were randomly assigned to 4 groups(n=5 in each group),including a control group,a liver cirrhosis group,an osteoporosis group,and a cirrhosis and osteoporosis comorbidity group.Pathological changes in the liver were observed via HE staining,Sirius Red staining,and serum liver function indicators.Bone mass and morphological changes were assessed using micro-CT and HE staining.ELISA,Western blot,and immunohistochemistry were performed to assess the expression of insulin-like growth factor-1(IGF-1)in serum and liver tissues.An additional IGF-1 intervention group was established to investigate the potential role of IGF-1 in the comorbidity of liver cirrhosis and osteoporosis,and changes in bone mass and morphology were analyzed via micro-CT and HE staining.Results Compared with the control and osteoporosis groups,the liver cirrhosis and cirrhosis-osteoporosis comorbidity groups exhibited significant inflammatory cell infiltration and collagen fiber deposition in liver tissues,along with markedly increased serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBIL)(P＜0.05).According to the Micro-CT and HE staining results,the cirrhosis-osteoporosis comorbidity group showed reduced bone mass and decreased trabecular numbers in the distal femur compared to those in the osteoporosis group,with the differences being statistically significant(P＜0.05).ELISA,Western blot,and immunohistochemistry demonstrated significantly reduced expression of IGF-1 in the liver and serum of the cirrhosis-osteoporosis comorbidity group(P＜0.05).Notably,exogenous IGF-1 treatment restored bone mass in mice with liver cirrhosis combined with osteoporosis(P＜0.05).Conclusion Through ovariectomy combined with CCl4 induction,a mouse model of liver cirrhosis combined with osteoporosis was successfully established.IGF-1 may serve as a potential molecular mechanism and therapeutic target mediating the liver cirrhosis-osteoporosis comorbidity.

Objective:To investigate the value of coronary CTA (CCTA)-based traditional features and radiomics of plaque in the identification of culprit lesions that caused acute myocardial infarction (AMI).Methods:This was a retrospective multicenter study. From July 2016 to November 2023, a total of 344 patients from the Affiliated Hospital of Qingdao University (training cohort, n=184), Shandong Provincial Hospital Affiliated to Shandong First Medical University (validation cohort, n=88) and Qilu Hospital of Shandong University (test cohort, n=72) who received percutaneous coronary intervention (PCI) due to AMI and underwent CCTA within 48 hours of AMI were enrolled. The culprit plaques and non-culprit plaques were identified using a combination of electrocardiogram, CCTA, and angiographic findings. The vessel, plaque location, plaque type, Coronary Artery Disease-Reporting and Data System (CAD-RADS) score, high-risk plaque characteristics, plaque length, plaque volume, and burden were analyzed, and 1 904 radiomics features were extracted for each plaque. The traditional imaging model, the radiomics model, and the combined model were established by using multivariate Logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each model in identifying culprit lesions. The DeLong test was used for the comparison of AUC between every two models. The net reclassification index (NRI) was used to evaluate the incremental value of the combined model to the traditional imaging model and the radiomics model. The decision curve analysis (DCA) was used to assess the clinical net benefit of these models. A correlation heatmap was used to evaluate the correlation between the radiomics score and traditional CCTA factors. The interpretable analysis of the decision process of the combined model was performed by the Shapley Additive exPlanations (SHAP). Results:In the validation cohort and the test cohort, the AUC of the traditional imaging model developed by the vessel, plaque type, positive remodeling and CAD-RADS score was 0.898 (95% CI 0.869-0.922) and 0.881 (95% CI 0.848-0.910), respectively. The radiomics model developed by six radiomics features was 0.863 (95% CI 0.831-0.891) and 0.863 (95% CI 0.827-0.864), respectively. The AUC of the combined model was 0.930 (95% CI 0.905-0.950)and 0.919 (95% CI 0.889-0.942), respectively. In the validation cohort and the test cohort, the AUC of the combined model was higher than that of the traditional imaging model ( Z=4.013, 4.272, P<0.001) and that of the radiomics model ( Z=4.819, 3.784, P<0.001), respectively. In the validation cohort, the combined model yielded an NRI of 20.43% (95% CI 10.43%-30.44%, P<0.001) and 20.21% (95% CI 9.62%-30.80%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. In the test cohort, the combined model yielded an NRI of 28.05% (95% CI 16.72%-39.38%, P<0.001) and 23.57% (95% CI 13.58%-33.56%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. DCA showed the combined model had the highest clinical net benefit. The correlation heatmap showed the radiomics score was not correlated or only weakly correlated with traditional CCTA factors. SHAP indicated the radiomics and CAD-RADS score contributed significantly to the model. Conclusion:The CCTA-based traditional features and radiomics of plaque have favorable performance for the identification of culprit plaques in patients with AMI.

Objective·To quantify brain iron content in Parkinson's disease(PD)patients by using quantitative susceptibility mapping(QSM)based on phase linearity fitting.Combined with texture analysis methods,the magnetic susceptibility distribution characteristics of gray matter nuclei in PD patients were quantitatively analyzed with multiple parameters and dimensions,and the sensitivity of texture features was evaluated with clinical scoring.Methods·Quantitative susceptibility images from 20 PD patients and 20 healthy controls(HC)were analyzed retrospectively.Regions of interest in basal ganglia were manually segmented,followed by three-dimensional texture analysis by using gray-level run-length matrix(GLRLM).One-way analysis of variance(ANOVA)was performed to compare differences between the two groups,and the bilateral Pearson linear correlation coefficient(r)was calculated to evaluate the correlation between texture parameters and UPDRS-Ⅲ clinical scores.Results·The analysis of texture feature parameters showed that there were significant differences between the PD and HC groups in the gray matter nuclei.Among all the texture feature parameters of GLRLM,LngREnch showed significant differences between the PD group and the HC group in the five gray matter nuclei measured.The average magnetic susceptibility of gray matter nuclei and GLRLM texture parameters were sensitive in distinguishing PD from HC(AUC＞0.5).The AUC values of RLNonUni,LngREnch,ShrtREmp,and Fraction were higher than that of the average magnetization susceptibiliyt.The correlation analysis showed that RLNonUni and GLevNonU in the caudate nucleus(CN),as well as GLevNonU in the red nucleus(RN),were significantly correlated with UPDRS-Ⅲ scores,while no significant clinical correlations were found for the remaining parameters.Conclusion·Compared to the mean magnetic susceptibility values,GLRLM texture parameters provide better differentiation between the PD and HC groups.Multiparameter texture analysis offers a novel approach to QSM-based quantitative assessment of brain iron content,which can provide additional multidimensional quantitative information for the non-invasive diagnosis of PD.

Objective To compare the efficacy and safety of defocus incorporated soft contact lenses(DISC)and orthokeratology(Ortho-K)for myopia control in children aged 8～15 years,and to further investigate the influence of dif-ferent baseline age and spherical equivalent(SE)on the treatment effect.Methods A retrospective cohort study was conducted,involving 197 myopic children(197 eyes)aged 8～15 years who were fitted with contact lenses at the Depart-ment of Ophthalmology,Xi'an People's Hospital(Xi'an Fourth Hospital)from May to September 2023.They were divid-ed into the DISC group(97 cases)and the Ortho-K group(100 cases).After 12 months of continuous follow-up,the chan-ges in axial length(AL)at 3,6,and 12 months after lens wear were compared between the two groups.Subgroup analysis was then performed:participants were divided into a younger subgroup(8～10 years)and an older subgroup(11～15 years)based on pre-wear age,and into a low myopia subgroup(-1.00～-3.00 D)and a moderate myopia subgroup(-3.25～-6.00 D)based on pre-wear SE.The AL changes at 3,6,and 12 months after wearing DISC or Ortho-K were com-pared between groups within these subgroups.Meanwhile,the incidence of conjunctivitis,incidence of corneal staining,corneal endothelial cell density,and corneal thickness were compared between the two groups at 12 months after lens wear.Results Inter-group comparisons showed:The change in AL in the DISC group at 3 months after lens wear was significantly lower than that in the Ortho-K group,and the difference was statistically significant(P＜0.05);at 6 and 12 months after lens wear,the differences in AL change between the two groups were not statistically significant(both P＞0.05).Subgroup analysis by age and SE showed:In the younger subgroup and the low myopia subgroup,the AL change in the DISC group at 3 months after lens wear was significantly lower than that in the Ortho-K group,and the differences were statistically significant(both P＜0.05),but these differences disappeared at 6 and 12 months after lens wear(all P＞0.05);in the older subgroup and the moderate myopia subgroup,the differences in AL change between the two groups at 3,6,and 12 months after lens wear were not statistically significant(all P＞0.05).At 12 months after lens wear,there were no statistically significant differences in the incidence of conjunctivitis,incidence of corneal staining,corneal endothe-lial cell density,or corneal thickness between the DISC and Ortho-K groups(all P＞0.05).Conclusion DISC demon-strates superior myopia control efficacy in the short term(3 months)for younger children and those with low myopia,but its medium-term(6 months)and long-term(12 months)efficacy converges with that of Ortho-K.Furthermore,the long-term safety of DISC is not significantly different from that of Ortho-K.

Objective:To explore the level of positive psychological capital and its trends in traumatic lower limb amputation patients during the 15 months after surgery, and to identify the time period when the patients' level of positive psychological capital is weak, so as to provide a basis for interventions.Methods:This study was a prospective longitudinal study. Convenience sampling was used to select 143 patients with traumatic lower limb amputation admitted to the Department of Emergency Medicine of the First Affiliated Hospital of Zhengzhou University from January 2021 to November 2022 for the study. General information questionnaire, Positive Psychological-Capital Questionnaire (PPQ) were used on the third postoperative day (T1) , on the day of discharge (T2) , 1 month (T3) , 2 months (T4) , 3 months (T5) , 6 months (T6) , 9 months (T7) , 12 months (T8) , and 15 months (T9) after discharge for a total of nine time points to administer the questionnaire to the patients. One-way repeated-measures ANOVA and plotting of results were performed on the nine time-point data using Graph Pad prism 9.5 software and SPSS 21.0 software, and the data were compared two-by-two using the Bonferroni multiple comparison test.Results:There were 143, 139, 132, 129, 122, 120, 119, 118, and 116 patients who participated in the survey from T1 to T9 time points, with a loss to follow-up rate of 18.88% (27/143) . PPQ scores of 116 traumatic lower limb amputation patients at nine time points were (103.25±9.03) , (108.53±9.32) , (104.38±9.60) , (99.71±9.61) , (95.82±9.55) , (91.49±9.41) , (93.34±9.29) , (93.53±9.14) , (93.62±9.05) , and the mean PPQ scores were lower than the theoretical mean (104) at all time points except T2 and T3 time points. One-way repeated-measures ANOVA showed that the difference in the change in the level of positive psychological capital of patients after traumatic lower limb amputation from postoperative day 3 to 15 months after discharge was statistically significant ( F=990.144, P<0.01) . Bonferroni's multiple comparison test showed that there was no statistically significant difference in two-by-two comparisons between T7, T8, and T9 time points with each other ( P>0.05) , and the rest of the two-by-two comparisons were statistically significant ( P<0.05) . Changes in the total PPQ score and the curves of the self-efficacy dimension, resilience dimension, hope dimension, and optimism dimension scores all showed a trend of a brief increase, followed by a continuous decrease, and then a slow increase to a plateau. Conclusions:Traumatic lower limb amputation patients show a wide range of changes in positive psychological capital levels from postoperative day 3 to 15 months after discharge, with a trend of a brief increase at discharge, followed by a steady decline, and then a slow increase to a plateau. Healthcare professionals should pay dynamic attention to the psychological state and psychological strength of patients after traumatic lower limb amputation and provide targeted interventions at different stages after discharge.

Objective To compare the efficacy and safety of defocus incorporated soft contact lenses(DISC)and orthokeratology(Ortho-K)for myopia control in children aged 8～15 years,and to further investigate the influence of dif-ferent baseline age and spherical equivalent(SE)on the treatment effect.Methods A retrospective cohort study was conducted,involving 197 myopic children(197 eyes)aged 8～15 years who were fitted with contact lenses at the Depart-ment of Ophthalmology,Xi'an People's Hospital(Xi'an Fourth Hospital)from May to September 2023.They were divid-ed into the DISC group(97 cases)and the Ortho-K group(100 cases).After 12 months of continuous follow-up,the chan-ges in axial length(AL)at 3,6,and 12 months after lens wear were compared between the two groups.Subgroup analysis was then performed:participants were divided into a younger subgroup(8～10 years)and an older subgroup(11～15 years)based on pre-wear age,and into a low myopia subgroup(-1.00～-3.00 D)and a moderate myopia subgroup(-3.25～-6.00 D)based on pre-wear SE.The AL changes at 3,6,and 12 months after wearing DISC or Ortho-K were com-pared between groups within these subgroups.Meanwhile,the incidence of conjunctivitis,incidence of corneal staining,corneal endothelial cell density,and corneal thickness were compared between the two groups at 12 months after lens wear.Results Inter-group comparisons showed:The change in AL in the DISC group at 3 months after lens wear was significantly lower than that in the Ortho-K group,and the difference was statistically significant(P＜0.05);at 6 and 12 months after lens wear,the differences in AL change between the two groups were not statistically significant(both P＞0.05).Subgroup analysis by age and SE showed:In the younger subgroup and the low myopia subgroup,the AL change in the DISC group at 3 months after lens wear was significantly lower than that in the Ortho-K group,and the differences were statistically significant(both P＜0.05),but these differences disappeared at 6 and 12 months after lens wear(all P＞0.05);in the older subgroup and the moderate myopia subgroup,the differences in AL change between the two groups at 3,6,and 12 months after lens wear were not statistically significant(all P＞0.05).At 12 months after lens wear,there were no statistically significant differences in the incidence of conjunctivitis,incidence of corneal staining,corneal endothe-lial cell density,or corneal thickness between the DISC and Ortho-K groups(all P＞0.05).Conclusion DISC demon-strates superior myopia control efficacy in the short term(3 months)for younger children and those with low myopia,but its medium-term(6 months)and long-term(12 months)efficacy converges with that of Ortho-K.Furthermore,the long-term safety of DISC is not significantly different from that of Ortho-K.

Objective·To quantify brain iron content in Parkinson's disease(PD)patients by using quantitative susceptibility mapping(QSM)based on phase linearity fitting.Combined with texture analysis methods,the magnetic susceptibility distribution characteristics of gray matter nuclei in PD patients were quantitatively analyzed with multiple parameters and dimensions,and the sensitivity of texture features was evaluated with clinical scoring.Methods·Quantitative susceptibility images from 20 PD patients and 20 healthy controls(HC)were analyzed retrospectively.Regions of interest in basal ganglia were manually segmented,followed by three-dimensional texture analysis by using gray-level run-length matrix(GLRLM).One-way analysis of variance(ANOVA)was performed to compare differences between the two groups,and the bilateral Pearson linear correlation coefficient(r)was calculated to evaluate the correlation between texture parameters and UPDRS-Ⅲ clinical scores.Results·The analysis of texture feature parameters showed that there were significant differences between the PD and HC groups in the gray matter nuclei.Among all the texture feature parameters of GLRLM,LngREnch showed significant differences between the PD group and the HC group in the five gray matter nuclei measured.The average magnetic susceptibility of gray matter nuclei and GLRLM texture parameters were sensitive in distinguishing PD from HC(AUC＞0.5).The AUC values of RLNonUni,LngREnch,ShrtREmp,and Fraction were higher than that of the average magnetization susceptibiliyt.The correlation analysis showed that RLNonUni and GLevNonU in the caudate nucleus(CN),as well as GLevNonU in the red nucleus(RN),were significantly correlated with UPDRS-Ⅲ scores,while no significant clinical correlations were found for the remaining parameters.Conclusion·Compared to the mean magnetic susceptibility values,GLRLM texture parameters provide better differentiation between the PD and HC groups.Multiparameter texture analysis offers a novel approach to QSM-based quantitative assessment of brain iron content,which can provide additional multidimensional quantitative information for the non-invasive diagnosis of PD.

Objective:To investigate the value of coronary CTA (CCTA)-based traditional features and radiomics of plaque in the identification of culprit lesions that caused acute myocardial infarction (AMI).Methods:This was a retrospective multicenter study. From July 2016 to November 2023, a total of 344 patients from the Affiliated Hospital of Qingdao University (training cohort, n=184), Shandong Provincial Hospital Affiliated to Shandong First Medical University (validation cohort, n=88) and Qilu Hospital of Shandong University (test cohort, n=72) who received percutaneous coronary intervention (PCI) due to AMI and underwent CCTA within 48 hours of AMI were enrolled. The culprit plaques and non-culprit plaques were identified using a combination of electrocardiogram, CCTA, and angiographic findings. The vessel, plaque location, plaque type, Coronary Artery Disease-Reporting and Data System (CAD-RADS) score, high-risk plaque characteristics, plaque length, plaque volume, and burden were analyzed, and 1 904 radiomics features were extracted for each plaque. The traditional imaging model, the radiomics model, and the combined model were established by using multivariate Logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each model in identifying culprit lesions. The DeLong test was used for the comparison of AUC between every two models. The net reclassification index (NRI) was used to evaluate the incremental value of the combined model to the traditional imaging model and the radiomics model. The decision curve analysis (DCA) was used to assess the clinical net benefit of these models. A correlation heatmap was used to evaluate the correlation between the radiomics score and traditional CCTA factors. The interpretable analysis of the decision process of the combined model was performed by the Shapley Additive exPlanations (SHAP). Results:In the validation cohort and the test cohort, the AUC of the traditional imaging model developed by the vessel, plaque type, positive remodeling and CAD-RADS score was 0.898 (95% CI 0.869-0.922) and 0.881 (95% CI 0.848-0.910), respectively. The radiomics model developed by six radiomics features was 0.863 (95% CI 0.831-0.891) and 0.863 (95% CI 0.827-0.864), respectively. The AUC of the combined model was 0.930 (95% CI 0.905-0.950)and 0.919 (95% CI 0.889-0.942), respectively. In the validation cohort and the test cohort, the AUC of the combined model was higher than that of the traditional imaging model ( Z=4.013, 4.272, P<0.001) and that of the radiomics model ( Z=4.819, 3.784, P<0.001), respectively. In the validation cohort, the combined model yielded an NRI of 20.43% (95% CI 10.43%-30.44%, P<0.001) and 20.21% (95% CI 9.62%-30.80%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. In the test cohort, the combined model yielded an NRI of 28.05% (95% CI 16.72%-39.38%, P<0.001) and 23.57% (95% CI 13.58%-33.56%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. DCA showed the combined model had the highest clinical net benefit. The correlation heatmap showed the radiomics score was not correlated or only weakly correlated with traditional CCTA factors. SHAP indicated the radiomics and CAD-RADS score contributed significantly to the model. Conclusion:The CCTA-based traditional features and radiomics of plaque have favorable performance for the identification of culprit plaques in patients with AMI.

Objective:To explore the level of positive psychological capital and its trends in traumatic lower limb amputation patients during the 15 months after surgery, and to identify the time period when the patients' level of positive psychological capital is weak, so as to provide a basis for interventions.Methods:This study was a prospective longitudinal study. Convenience sampling was used to select 143 patients with traumatic lower limb amputation admitted to the Department of Emergency Medicine of the First Affiliated Hospital of Zhengzhou University from January 2021 to November 2022 for the study. General information questionnaire, Positive Psychological-Capital Questionnaire (PPQ) were used on the third postoperative day (T1) , on the day of discharge (T2) , 1 month (T3) , 2 months (T4) , 3 months (T5) , 6 months (T6) , 9 months (T7) , 12 months (T8) , and 15 months (T9) after discharge for a total of nine time points to administer the questionnaire to the patients. One-way repeated-measures ANOVA and plotting of results were performed on the nine time-point data using Graph Pad prism 9.5 software and SPSS 21.0 software, and the data were compared two-by-two using the Bonferroni multiple comparison test.Results:There were 143, 139, 132, 129, 122, 120, 119, 118, and 116 patients who participated in the survey from T1 to T9 time points, with a loss to follow-up rate of 18.88% (27/143) . PPQ scores of 116 traumatic lower limb amputation patients at nine time points were (103.25±9.03) , (108.53±9.32) , (104.38±9.60) , (99.71±9.61) , (95.82±9.55) , (91.49±9.41) , (93.34±9.29) , (93.53±9.14) , (93.62±9.05) , and the mean PPQ scores were lower than the theoretical mean (104) at all time points except T2 and T3 time points. One-way repeated-measures ANOVA showed that the difference in the change in the level of positive psychological capital of patients after traumatic lower limb amputation from postoperative day 3 to 15 months after discharge was statistically significant ( F=990.144, P<0.01) . Bonferroni's multiple comparison test showed that there was no statistically significant difference in two-by-two comparisons between T7, T8, and T9 time points with each other ( P>0.05) , and the rest of the two-by-two comparisons were statistically significant ( P<0.05) . Changes in the total PPQ score and the curves of the self-efficacy dimension, resilience dimension, hope dimension, and optimism dimension scores all showed a trend of a brief increase, followed by a continuous decrease, and then a slow increase to a plateau. Conclusions:Traumatic lower limb amputation patients show a wide range of changes in positive psychological capital levels from postoperative day 3 to 15 months after discharge, with a trend of a brief increase at discharge, followed by a steady decline, and then a slow increase to a plateau. Healthcare professionals should pay dynamic attention to the psychological state and psychological strength of patients after traumatic lower limb amputation and provide targeted interventions at different stages after discharge.