Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Ferroptosis has received great attention as an iron-dependent programmed cell death for efficient cancer therapy. However, with the accumulation of iron in tumor cells, the antioxidant system is activated by reducing glutathione (GSH) with glutathione peroxidase 4 (GPX4), which critically limits the ferroptosis therapeutic effect. Herein, an iron and GPX4 silencing siRNA (siGPX4) co-encapsulated ferritin nanocage (HFn@Fe/siGPX4) was developed to enhance ferroptosis by disruption of redox homeostasis and inhibition of antioxidant enzyme synergistically. The siGPX4 were loaded into the nanocages by pre-incubated with iron, which could significantly improve the loading efficiency of the gene drugs when compared with the reported gene drug loading strategy by ferritin nanocages. And more iron was overloaded into the ferritin through the diffusion method. When HFn@Fe/siGPX4 was taken up by human breast cancer cell MCF-7 in a TfR1-mediated pathway, the excess iron ions in the drug delivery system could for one thing induce ferroptosis by the production of reactive oxygen species (ROS), for another promote siGPX4 escaping from the lysosome to exert gene silencing effect more effectively. Both the in vitro and in vivo results demonstrated that HFn@Fe/siGPX4 could significantly inhibit tumor growth by synergistical ferroptosis. Thus, the developed HFn@Fe/siGPX4 afforded a combined ferroptosis strategy for ferroptosis-based antitumor as well as a novel and efficient gene drug delivery system.

Objective To observe value of real-time functional MRI neurofeedback(rtfMRI-NF)for modulating brain activity changes in obese adults.Methods Twenty-two obese adults were prospectively recruited,3-week rtfMRI-NF training intervention was conducted.Barratt impulsivityness scale version 11(BIS-11),three-factor eating questionnaire(TFEQ)and food rating scales were scored before and after intervention,and whole-brain resting state fMRI(rs-fMRI)data were obtained.Clinical scale scores,rs-fMRI regional homogeneity(ReHo)values and amplitude of low frequency fluctuation(ALFF)values were compared before and after intervention.Then brain regions with differences of ReHo and ALFF values before and after intervention were explored,and correlations of values of rs-fMRI data differences and clinical scale score differences were analyzed.Results BIS-11 score,TFEQ emotional eating(TFEQ-EE)score and food rating scales scores decreased,while TFEQ cognitive restraint(TFEQ-CR)scores increased in obese adults after intervention(all P＜0.05).ReHo values in right inferior frontal gyrus,right anterior cingulate and left precuneus increased,while of left middle temporal gyrus decreased(all corrected P＜0.05).ALFF values of left precuneus increased,whereas of left middle occipital gyrus,right superior occipital gyrus,left calcarine fissure and surrounding cortex and left supramarginal and angular gyrus decreased(all corrected P＜0.05).ReHo difference in right anterior cingulate was negatively correlated with BIS-11 scores difference(r=-0.601,P＜0.05),and ALFF difference in left precuneus was negatively correlated with TFEQ-EE difference(r=-0.478,P＜0.05).Conclusion rtfMRI-NF intervention could correct disorder of cerebral functional areas in obese adults and change high-calorie food preference and poor dietary habits.

Objective To evaluate answers to typical clinical questions related to neuro-ophthalmology generated by Artificial Intelligence(AI)Large Language Models(LLM)and to explore the performance of neuro-ophthalmology-related questions on LLM in a multidimensional manner using objective and expert assessment.Methods Multicenter,random-ized,cross-sectional pilot study.Thirty typical questions related to neuro-ophthalmology were selected based on four per-spectives:definition,etiology,clinical manifestations and signs,and treatment and prognosis,and were analyzed quantita-tively using Deepseek,Wenxin Yiyin 4.0,Doubao,and Kimi 1.5,which are four open-source LLMs in China,and quantita-tively analyzed with objective assessment;and quantitatively rated by three ophthalmologists using expert assessment for 120 answer texts.Three ophthalmology experts quantitatively scored the 120 answer texts.Three ophthalmologists quantita-tively scored the 120 answer texts.Level 3,5,and 4 Likert scales were developed according to the completeness,accura-cy,professionalism,relevance,and criticality of the question texts,respectively.The best-performing LLM was selected,and its performance was observed across the four types of questions.Additionally,three other experts assessed whether the best-performing one could be evaluated as a substitute for real-world doctor-patient communication.Results In the objective Chinese text reading difficulty analysis,the differences in total word count among the four LLMs were statistically significant(all P＜0.001).Of the four LLMs,Kimi 1.5 performed the best,with frequencies of 61％,29％,and 41％for the highest scores in completeness(3),accuracy and professionalism(5),and relevance and usefulness(4),respective-ly.Kimi 1.5 performed more consistently on the questions on the four areas of neuro-ophthalmologic disorders:definition,etiology,clinical manifestations and signs,treatment,and prognosis,with no between-group differences(P＞0.05).Con-clusion Chinese language LLMs have great potential in the clinical application of neuro-ophthalmology.Kimi 1.5 outper-forms other LLMs in terms of completeness,accuracy,professionalism,relevance,and usefulness,but it still cannot re-place real-world doctor-patient communication.There is a need to explore new diagnostic and therapeutic model of AI+physician in the future.

Objective To evaluate answers to typical clinical questions related to neuro-ophthalmology generated by Artificial Intelligence(AI)Large Language Models(LLM)and to explore the performance of neuro-ophthalmology-related questions on LLM in a multidimensional manner using objective and expert assessment.Methods Multicenter,random-ized,cross-sectional pilot study.Thirty typical questions related to neuro-ophthalmology were selected based on four per-spectives:definition,etiology,clinical manifestations and signs,and treatment and prognosis,and were analyzed quantita-tively using Deepseek,Wenxin Yiyin 4.0,Doubao,and Kimi 1.5,which are four open-source LLMs in China,and quantita-tively analyzed with objective assessment;and quantitatively rated by three ophthalmologists using expert assessment for 120 answer texts.Three ophthalmology experts quantitatively scored the 120 answer texts.Three ophthalmologists quantita-tively scored the 120 answer texts.Level 3,5,and 4 Likert scales were developed according to the completeness,accura-cy,professionalism,relevance,and criticality of the question texts,respectively.The best-performing LLM was selected,and its performance was observed across the four types of questions.Additionally,three other experts assessed whether the best-performing one could be evaluated as a substitute for real-world doctor-patient communication.Results In the objective Chinese text reading difficulty analysis,the differences in total word count among the four LLMs were statistically significant(all P＜0.001).Of the four LLMs,Kimi 1.5 performed the best,with frequencies of 61％,29％,and 41％for the highest scores in completeness(3),accuracy and professionalism(5),and relevance and usefulness(4),respective-ly.Kimi 1.5 performed more consistently on the questions on the four areas of neuro-ophthalmologic disorders:definition,etiology,clinical manifestations and signs,treatment,and prognosis,with no between-group differences(P＞0.05).Con-clusion Chinese language LLMs have great potential in the clinical application of neuro-ophthalmology.Kimi 1.5 outper-forms other LLMs in terms of completeness,accuracy,professionalism,relevance,and usefulness,but it still cannot re-place real-world doctor-patient communication.There is a need to explore new diagnostic and therapeutic model of AI+physician in the future.

Objective To observe value of real-time functional MRI neurofeedback(rtfMRI-NF)for modulating brain activity changes in obese adults.Methods Twenty-two obese adults were prospectively recruited,3-week rtfMRI-NF training intervention was conducted.Barratt impulsivityness scale version 11(BIS-11),three-factor eating questionnaire(TFEQ)and food rating scales were scored before and after intervention,and whole-brain resting state fMRI(rs-fMRI)data were obtained.Clinical scale scores,rs-fMRI regional homogeneity(ReHo)values and amplitude of low frequency fluctuation(ALFF)values were compared before and after intervention.Then brain regions with differences of ReHo and ALFF values before and after intervention were explored,and correlations of values of rs-fMRI data differences and clinical scale score differences were analyzed.Results BIS-11 score,TFEQ emotional eating(TFEQ-EE)score and food rating scales scores decreased,while TFEQ cognitive restraint(TFEQ-CR)scores increased in obese adults after intervention(all P＜0.05).ReHo values in right inferior frontal gyrus,right anterior cingulate and left precuneus increased,while of left middle temporal gyrus decreased(all corrected P＜0.05).ALFF values of left precuneus increased,whereas of left middle occipital gyrus,right superior occipital gyrus,left calcarine fissure and surrounding cortex and left supramarginal and angular gyrus decreased(all corrected P＜0.05).ReHo difference in right anterior cingulate was negatively correlated with BIS-11 scores difference(r=-0.601,P＜0.05),and ALFF difference in left precuneus was negatively correlated with TFEQ-EE difference(r=-0.478,P＜0.05).Conclusion rtfMRI-NF intervention could correct disorder of cerebral functional areas in obese adults and change high-calorie food preference and poor dietary habits.

Objective:To summarize the clinical features of epilepsy and (or) developmental delay associated with KCNB1 gene variants in children.Methods:A case series study was conducted on 24 children with KCNB1 gene variants associated with epilepsy and (or) developmental delay who were treated at the Children′s Medical Center of Peking University First Hospital and the Department of Neurology of Shenzhen Children′s Hospital from July 2015 to June 2024. The manifestations of seizures, electroencephalogram (EEG) and genetic test results of those children were analyzed.Results:All the KCNB1 gene variants were de novo, involving 20 different variation, including 15 missense variations, 3 frameshift variations and 2 nonsense variations. There were 7 novel variations. Among the 24 developmental and epileptic encephalopathy children, there were 14 boys and 10 girls. The last follow-up age ranged from 9 months to 13 years and 9 months. Seizures were present in 21 children (88%), with onset ranging from 1 month to 7 years, and 76% (16/21) began before 2 years of age. The seizure types included focal seizures in 15 children (71%), epileptic spasms, myoclonic seizures, and generalized tonic-clonic seizures in 6 children respectively, atypical absence seizures in 4 children, and myoclonic atonic seizures in 1 child. Seventeen children (81%) had a cluster of seizures and 5 had a history of focal status epilepticus with impaired consciousness. All 24 children had varying degrees of developmental delay, with 3 presenting solely developmental delay. EEG abnormalities were present in all the 21 children with seizures, including focal or multifocal discharges in 20 children, generalized discharges in 10 children, hypsarrhythmia in 2 children, and electrical status epilepticus during sleep in 3 children. Magnetic resonance imaging abnormalities were found in 5 of the 24 children. Among the 21 children with seizures, 57% (12/21) achieved seizure control.Conclusions:KCNB1 gene variants are predominantly de novo missense variation. Most affected children present with epilepsy, though some may exhibit only developmental delay. Epilepsy often begins before 2 years of age, with focal seizures being the most common type. About 80% of patients experience clustered seizures. Although most patients achieve seizure control, they still exhibit varying degrees of developmental delay, consistent with developmental epileptic encephalopathy.

Objective:To analyze the clinical characteristics of ulcerative colitis (UC) in Han and Uyghur patients in Xinjiang Uygur Autonomous Region.Method:Data of UC patients hospitalized at the People′s Hospital of Xinjiang Uygur Autonomous Region from January 2015 to June 2023 were retrospectively collected, with a focus on the differences in basic information, extraintestinal manifestations and biochemical laboratory indicators between Han and Uyghur patients.Results:A total of 315 UC patients were included, with 172 Han cases (54.6%) and 143 Uyghur cases (45.4%) . Compared to the Han group, the Uyghur group had a higher proportion of females, a lower average age, and lower rates of smoking and alcohol consumption (all P<0.05) . The Uyghur group showed a higher prevalence of hepatobiliary diseases and joint injuries as extraintestinal manifestations, although the differences were not statistically significant ( P all>0.05) . The Han group had a statistically significant higher level of intraepithelial neoplasia (χ 2 = 5.075, P<0.05) . The Uyghur group exhibited significantly higher levels of white blood cell count, platelet count, neutrophils, lymphocyte count, globulin, C-reactive protein, erythrocyte sedimentation rate, highly sensitive C-reactive protein, anti-neutrophil cytoplasmic antibodies, and H.pylori antibodies compared to the Han group (all P<0.05) . Both Han and Uyghur UC patients achieved satisfactory clinical efficacy. Conclusion:Uyghur UC patients have distinct characteristics, including a younger age of onset and more severe disease course, yet appropriate treatment can lead to satisfactory clinical outcomes.