Objective To characterize neurological alterations associated with structural bowel damage in patients with Crohn's disease(CD)through radiomics-assisted neurophenotyping,utilizing multiparametric brain MRI.Methods This prospective study enrolled patients with CD who underwent brain MRI,MR enterography,and ileocolonoscopy within one week.The Lémann Index was used to quantitatively assess cumulative structural bowel damage.CD patients were stratified into two groups based on a cutoff value of 4.8:those with bowel damage(LI>4.8)and those without bowel damage(LI≤4.8).A neurophenotype model was developed to characterize the neural changes associated with bowel damage in CD.Key features were selected from first-order features extracted from multiparametric brain MRI in the training cohort and validated in an independent test cohort.Results The final study population comprised 109 patients,including 51 individuals with bowel damage and 58 without bowel damage.The neurophenotype model scores were 0.785(95%CI:0.506～0.945)in the bowel damage group and 0.155(95%CI:0.093～0.394)in the non-bowel damage group,showing a statistically significant difference between the two groups(P<0.001).The developed model exhibited strong discriminative performance,with area under the receiver operating characteristic curve(AUC)values ranging from 0.824 to 0.918 across the training,vali-dation,and test cohorts(all P<0.05).Conclusion Our radiomics-assisted neurophenotype analysis reveals neural alterations in CD patients with bowel damage,which may indicate extraintestinal manifestations associated with cumulative intestinal injury.

Objective:To analyze the clinical features and diagnostic process of ring chromosome syndrome.Methods:Clinical data of 9 children with ring chromosome syndrome who were treated at the Children′s Medical Center of Peking University First Hospital from September 2009 to May 2025, were summarized and analyzed in a case series study. The data included clinical manifestations, types of epileptic seizures, genetic testing, treatment outcomes, and follow-up results, et al.Results:Among the 9 children with ring chromosome syndrome, there were 6 girls and 3 boys, including 4 children with ring chromosome 20 syndrome, 3 children with ring chromosome 14 syndrome, and 1 child each with ring chromosome 13 and 17 syndrome. All 9 children had de novo chromosomal variations. Among them, 3 children of ring chromosome 20 syndrome were mosaic, and the remaining 6 children were non-mosaic. All 9 children exhibited diverse clinical features, especially those with ring chromosome 20 syndrome, which presented with specific manifestations. The 4 children with ring chromosome 20 syndrome all had acute epileptic seizures as the initial symptom, with onset ages of 67, 39, 17, and 96 months, and all had focal seizures. One child with ring chromosome 20 syndrome had non-convulsive status epilepticus. Development of all 4 children with ring chromosome 20 syndrome was normal before seizure onset, but 3 children showed regression after onset. No physical deformities were observed in 4 children with ring chromosome 20 syndrome, and 2 children were misdiagnosed, 3 children underwent whole exome sequencing and copy number variation analysis in their families, with no abnormalities detected. All 4 children with ring chromosome 20 syndrome were diagnosed through chromosomal karyotype analysis, the intervals between onset and diagnosis were 2, 81, 19 and 13 months, respectively. Follow-up showed that epileptic seizures were not controlled in all 4 children with ring chromosome 20 syndrome. The other 5 children were characterized by developmental delay as the initial symptom, followed by epileptic seizures between 3 and 24 months of age. Developmental regression of the other 5 children did not occur after onset, 2 of them had microcephaly, and 3 had wide-set eyes. No misdiagnoses were reported in these 5 children, and the intervals between onset and diagnosis were 7, 3, 55, 3, and 106 months, respectively. Follow-up showed that epileptic seizures were controlled in these 5 children. Conclusions:Ring chromosome 20 syndrome typically manifest with epilepsy as the initial symptom and are refractory to drug treatment, their early development is entirely normal. Ring chromosome 13, 14, and 17 syndrome are characterized by developmental delay from an early age, followed by the onset of epileptic seizures, which are easily controlled. Conventional whole exome sequencing and copy number variation analysis in families rarely detect ring chromosome abnormalities. Early chromosomal karyotype analysis is essential for the diagnosis of ring chromosome syndrome.

AIM:This study aims to investigate the molecular mechanism by which tubeimoside I(TBMS1)inhibits Snail expression in pancreatic cancer cells(PANC-1).METHODS:Human pancreatic cancer PANC-1 cells were cultured in vitro.The inhibitory effect of TBMS1 on PANC-1 cells was assessed using the MTT assay,and the data were analyzed based on the IC50 value of TBMS1.The impact of TBMS1 on the clonal formation ability of PANC-1 cells was evaluated through colony formation assays.The Transwell assay was employed to assess the effect of TBMS1 on the migrato-ry capability of PANC-1 cells.Apoptosis and cell cycle alterations in PANC-1 cells were analyzed using acridine orange staining and flow cytometry.The expression of Snail protein in pancreatic cancer and its relationship with survival of the patients were analyzed using the GEPIA database and Kaplan-Meier Plotter data.Immunofluorescence staining was con-ducted to investigate the effect of TBMS1 on Snail expression,while Western blot was used to evaluate the expression of poly(ADP-ribose)polymerase(PARP),E-cadherin and Snail in the cells.The ubiquitination of Snail protein was mea-sured using immunoprecipitation techniques.RESULTS:As the concentration of TBMS1 increased,the survival rate and number of clones formed by PANC-1 cells progressively decreased,leading to apoptosis,cleavage of PARP,and cell cycle arrest in the G1 phase.There was also a reduction in the proportion of cells in the S phase and a decrease in cell migration ability.The expression of Snail protein,a critical factor in cell migration,was inhibited,while E-cadherin protein levels were increased.Treatment with the proteasome inhibitor MG132 was able to reverse the suppression of Snail protein ex-pression caused by TBMS1.Immunoprecipitation results indicated that TBMS1 enhances the ubiquitination and subse-quent degradation of Snail protein.CONCLUSION:TBMS1 effectively inhibits the malignant progression of pancreatic cancer cells by promoting the ubiquitination and degradation of Snail protein in PANC-1 cells.

Objective To characterize neurological alterations associated with structural bowel damage in patients with Crohn's disease(CD)through radiomics-assisted neurophenotyping,utilizing multiparametric brain MRI.Methods This prospective study enrolled patients with CD who underwent brain MRI,MR enterography,and ileocolonoscopy within one week.The Lémann Index was used to quantitatively assess cumulative structural bowel damage.CD patients were stratified into two groups based on a cutoff value of 4.8:those with bowel damage(LI>4.8)and those without bowel damage(LI≤4.8).A neurophenotype model was developed to characterize the neural changes associated with bowel damage in CD.Key features were selected from first-order features extracted from multiparametric brain MRI in the training cohort and validated in an independent test cohort.Results The final study population comprised 109 patients,including 51 individuals with bowel damage and 58 without bowel damage.The neurophenotype model scores were 0.785(95%CI:0.506～0.945)in the bowel damage group and 0.155(95%CI:0.093～0.394)in the non-bowel damage group,showing a statistically significant difference between the two groups(P<0.001).The developed model exhibited strong discriminative performance,with area under the receiver operating characteristic curve(AUC)values ranging from 0.824 to 0.918 across the training,vali-dation,and test cohorts(all P<0.05).Conclusion Our radiomics-assisted neurophenotype analysis reveals neural alterations in CD patients with bowel damage,which may indicate extraintestinal manifestations associated with cumulative intestinal injury.

AIM:This study aims to investigate the molecular mechanism by which tubeimoside I(TBMS1)inhibits Snail expression in pancreatic cancer cells(PANC-1).METHODS:Human pancreatic cancer PANC-1 cells were cultured in vitro.The inhibitory effect of TBMS1 on PANC-1 cells was assessed using the MTT assay,and the data were analyzed based on the IC50 value of TBMS1.The impact of TBMS1 on the clonal formation ability of PANC-1 cells was evaluated through colony formation assays.The Transwell assay was employed to assess the effect of TBMS1 on the migrato-ry capability of PANC-1 cells.Apoptosis and cell cycle alterations in PANC-1 cells were analyzed using acridine orange staining and flow cytometry.The expression of Snail protein in pancreatic cancer and its relationship with survival of the patients were analyzed using the GEPIA database and Kaplan-Meier Plotter data.Immunofluorescence staining was con-ducted to investigate the effect of TBMS1 on Snail expression,while Western blot was used to evaluate the expression of poly(ADP-ribose)polymerase(PARP),E-cadherin and Snail in the cells.The ubiquitination of Snail protein was mea-sured using immunoprecipitation techniques.RESULTS:As the concentration of TBMS1 increased,the survival rate and number of clones formed by PANC-1 cells progressively decreased,leading to apoptosis,cleavage of PARP,and cell cycle arrest in the G1 phase.There was also a reduction in the proportion of cells in the S phase and a decrease in cell migration ability.The expression of Snail protein,a critical factor in cell migration,was inhibited,while E-cadherin protein levels were increased.Treatment with the proteasome inhibitor MG132 was able to reverse the suppression of Snail protein ex-pression caused by TBMS1.Immunoprecipitation results indicated that TBMS1 enhances the ubiquitination and subse-quent degradation of Snail protein.CONCLUSION:TBMS1 effectively inhibits the malignant progression of pancreatic cancer cells by promoting the ubiquitination and degradation of Snail protein in PANC-1 cells.

Objective:To analyze the clinical features and diagnostic process of ring chromosome syndrome.Methods:Clinical data of 9 children with ring chromosome syndrome who were treated at the Children′s Medical Center of Peking University First Hospital from September 2009 to May 2025, were summarized and analyzed in a case series study. The data included clinical manifestations, types of epileptic seizures, genetic testing, treatment outcomes, and follow-up results, et al.Results:Among the 9 children with ring chromosome syndrome, there were 6 girls and 3 boys, including 4 children with ring chromosome 20 syndrome, 3 children with ring chromosome 14 syndrome, and 1 child each with ring chromosome 13 and 17 syndrome. All 9 children had de novo chromosomal variations. Among them, 3 children of ring chromosome 20 syndrome were mosaic, and the remaining 6 children were non-mosaic. All 9 children exhibited diverse clinical features, especially those with ring chromosome 20 syndrome, which presented with specific manifestations. The 4 children with ring chromosome 20 syndrome all had acute epileptic seizures as the initial symptom, with onset ages of 67, 39, 17, and 96 months, and all had focal seizures. One child with ring chromosome 20 syndrome had non-convulsive status epilepticus. Development of all 4 children with ring chromosome 20 syndrome was normal before seizure onset, but 3 children showed regression after onset. No physical deformities were observed in 4 children with ring chromosome 20 syndrome, and 2 children were misdiagnosed, 3 children underwent whole exome sequencing and copy number variation analysis in their families, with no abnormalities detected. All 4 children with ring chromosome 20 syndrome were diagnosed through chromosomal karyotype analysis, the intervals between onset and diagnosis were 2, 81, 19 and 13 months, respectively. Follow-up showed that epileptic seizures were not controlled in all 4 children with ring chromosome 20 syndrome. The other 5 children were characterized by developmental delay as the initial symptom, followed by epileptic seizures between 3 and 24 months of age. Developmental regression of the other 5 children did not occur after onset, 2 of them had microcephaly, and 3 had wide-set eyes. No misdiagnoses were reported in these 5 children, and the intervals between onset and diagnosis were 7, 3, 55, 3, and 106 months, respectively. Follow-up showed that epileptic seizures were controlled in these 5 children. Conclusions:Ring chromosome 20 syndrome typically manifest with epilepsy as the initial symptom and are refractory to drug treatment, their early development is entirely normal. Ring chromosome 13, 14, and 17 syndrome are characterized by developmental delay from an early age, followed by the onset of epileptic seizures, which are easily controlled. Conventional whole exome sequencing and copy number variation analysis in families rarely detect ring chromosome abnormalities. Early chromosomal karyotype analysis is essential for the diagnosis of ring chromosome syndrome.

AIM:To investigate the molecular mechanism underlying ferroptosis induced by celastrol(Cel)in huamn pancreatic cancer cell line PANC-1.METHODS:The viability of PANC-1 cells was analyzed by MTT assay,and the effects of Cel on cell proliferation were analyzed using EdU and colony formation assays.Flow cytometry and fluores-cence microscopy were used to assess and observe changes in lipid reactive oxygen species(ROS)levels,respectively,while the levels of malondialdehyde(MDA),glutathione(GSH)and Fe2+were measured using specific kits.The protein expression of glutathione peroxidase 4(GPX4)was evaluated by Western blot,and GPX4 ubiquitination was measured by immunoprecipitation.RESULTS:It was found that the viability,proliferation and colony formation in PANC-1 cells de-creased gradually as the concentration of Cel increased.Addition of Cel alone to the cells reduced both cell rounding and viability,while treatment with ferrostatin-1(Fer-1)alone or in combination with Cel had no effect on either cell morpholo-gy or viability.Fluorescence staining of lipid ROS with BODIPYTM 581/591 C11 followed by flow cytometry analysis showed significantly increased levels of green fluorescence indicative of oxidized lipid ROS,which were further increased after treatment of the cells with Cel.Treatment of the cells with both Cel and Fer-1 reduced the green fluorescence and lip-id ROS levels.Treatment with Cel also increased the levels of MDA and Fe2+,relative to the controls,which reducing the levels of GSH,while addition of both Cel and Fer-1 to the cells restored the levels of MDA,Fe2+,and GSH to those of the control group.CONCLUSION:Treatment with Cel reduces the proliferation of pancreatic cancer cells by inducing fer-roptosis through promoting the ubiquitination and degradation of GPX4.

AIM:This study aimed to explore the induction of ferroptosis in non-small-cell lung cancer(NSCLC)cells by tubeimoside II(TBMS II)and to elucidate the underlying molecular mechanisms.METHODS:H460 NSCLC cells were cultured in vitro.Cell survival rates were assessed by using MTT assays,and doses of TBMS II resulting in below 50%survival were selected for further experimentation.Cell migration was evaluated using Transwell assays and the effects of TBMS II on H460 cell proliferation were assessed by colony formation assays.Flow cytometry and fluores-cence microscopy were used to assess changes in lipid peroxidation(lipid ROS),and the levels of GSH,T-AOC,MDA,and Fe2+were measured using commercial kits.Protein levels of GPX4,SLC7A11,FTH1,NCOA4,P62,and LC3 were examined using Western blot.Changes in mitochondrial structure were detected by transmission electron microscopy,and immunofluorescence was used to assess LC3 co-localization of FTH1 and NCOA4,as well as co-localization of LC3 and NCOA4 with lysosomes.RESULTS:Compared with the control group,TBMS II dose-dependently reduced H460 cell via-bility,migration,and clone formation,accompanied by the appearance of vacuoles within the cells.TBMS II treatment al-so led to decreased GSH and T-AOC levels,while increasing the cellular contents of MDA,indicating oxidative stress.Ad-ditionally,there was a decrease in the expression of the antioxidant proteins SLC7A11 and GPX4 in the cells,while lipid ROS and Fe2+levels were increased in proportion to the TBMS II concentration.The ferroptosis inhibitor ferrostatin-1 re-versed cell death caused by TBMS II,suggesting ferroptosis induction.Furthermore,increasing the TBMS II concentra-tion resulted in an upregulation of the autophagy marker proteins LC3 II/LC3 I and P62,indicative of increased autopha-gy.TBMS II also affected mitochondrial morphology in the cells,as seen in reduced mitochondrial fluorescence intensity.Protein expression of NCOA4 increased with higher TBMS II concentrations,while that of FTH1 decreased.Co-localiza-tion of LC3 II with FTH1 and NCOA4,as well as the lysosomal association of LC3 II and FTH1,also increased in a dose-dependent manner.CONCLUSION:TBMS II induces ferritinophagy in H460 cells,leading to decreased cell viability and increased ferroptosis.