Objective:To investigate the clinical characteristics of infantile cholestasis caused by IFT122 gene variants and the molecular mechanism underlying its impact on primary cilia.Methods:The clinical data of an infant with cholestasis from the Children′s Hospital of Fudan University in September 2022 were retrospectively analyzed. The whole-exome sequencing was performed to identify candidate variants, which were validated by Sanger sequencing in the family. Immortalized cell lines were generated using lentiviral infection, followed by immunofluorescence staining to assess the impact of the variants on primary cilia. Intergroup comparisons were performed using the independent sample t-test and Mann-Whitney U test .Results:The proband was a 4-month-old male infant presenting with jaundice, distinctive facial features, and sagittal craniosynostosis. Blood biochemistry indicated elevated direct bilirubin, total bile acids, and transaminases, with markedly increased γ-glutamyltransferase (GGT). Liver pathology demonstrated giant cell hepatitis with cholestasis and bile duct dysplasia. Genetic analysis identified compound heterozygous variants in IFT122 (NM_052989.3) gene c.88G>C (p.Ala30Pro) and c.240G>C (p.Trp80Cys), which co-segregated with the disease in the family. Immunofluorescence analysis demonstrated that the IFT122 gene compound heterozygous missense variants not only significantly reduced the proportion of cilia-positive cells but also led to aberrant ciliary localization of ADP-ribosylation factor-like protein 13B (ARL13B).In addition, ciliary deposition with phosphatidylinositol polyphosphate 5-phosphatase type Ⅳ (INPP5E) was reduced. All differences were statistically significant (all P<0.05). Conclusion:The compound heterozygous missense variants in IFT122 gene not only impair ciliogenesis but also disrupt the ciliary localization of ARL13B and INPP5E, ultimately resulting in high-GGT infantile cholestasis.

Objective:To investigate the clinical characteristics of infantile cholestasis caused by IFT122 gene variants and the molecular mechanism underlying its impact on primary cilia.Methods:The clinical data of an infant with cholestasis from the Children′s Hospital of Fudan University in September 2022 were retrospectively analyzed. The whole-exome sequencing was performed to identify candidate variants, which were validated by Sanger sequencing in the family. Immortalized cell lines were generated using lentiviral infection, followed by immunofluorescence staining to assess the impact of the variants on primary cilia. Intergroup comparisons were performed using the independent sample t-test and Mann-Whitney U test .Results:The proband was a 4-month-old male infant presenting with jaundice, distinctive facial features, and sagittal craniosynostosis. Blood biochemistry indicated elevated direct bilirubin, total bile acids, and transaminases, with markedly increased γ-glutamyltransferase (GGT). Liver pathology demonstrated giant cell hepatitis with cholestasis and bile duct dysplasia. Genetic analysis identified compound heterozygous variants in IFT122 (NM_052989.3) gene c.88G>C (p.Ala30Pro) and c.240G>C (p.Trp80Cys), which co-segregated with the disease in the family. Immunofluorescence analysis demonstrated that the IFT122 gene compound heterozygous missense variants not only significantly reduced the proportion of cilia-positive cells but also led to aberrant ciliary localization of ADP-ribosylation factor-like protein 13B (ARL13B).In addition, ciliary deposition with phosphatidylinositol polyphosphate 5-phosphatase type Ⅳ (INPP5E) was reduced. All differences were statistically significant (all P<0.05). Conclusion:The compound heterozygous missense variants in IFT122 gene not only impair ciliogenesis but also disrupt the ciliary localization of ARL13B and INPP5E, ultimately resulting in high-GGT infantile cholestasis.

In April 2025,the European Association for the Study of the Liver(EASL)released an updated edition of clinical practice guidelines on Wilson's disease,and compared with the 2012 edition,the updated guidelines perform detailed elaboration and updates on clinical manifestations,diagnostic algorithms,treatment strategies,and monitoring protocols,emphasize the role of serum exchangeable copper in the diagnosis and monitoring of Wilson's disease,and provide the reference ranges for clinical application.The updated guidelines also recommend and summarize the drugs for symptomatic treatment of neuropsychiatric symptoms,add a dedicated section on transitioning pediatric patients to adult care,and discuss the optimal timing,multidisciplinary team composition,and implementation frameworks of the transition plan.These updates fully reflect the latest evidence and the development of clinical needs in the diagnosis and treatment of Wilson's disease.This article gives an excerpt of the recommendations in the guidelines.

In April 2025， the European Association for the Study of the Liver （EASL） released an updated edition of clinical practice guidelines on Wilson’s disease， and compared with the 2012 edition， the updated guidelines perform detailed elaboration and updates on clinical manifestations， diagnostic algorithms， treatment strategies， and monitoring protocols， emphasize the role of serum exchangeable copper in the diagnosis and monitoring of Wilson’s disease， and provide the reference ranges for clinical application. The updated guidelines also recommend and summarize the drugs for symptomatic treatment of neuropsychiatric symptoms， add a dedicated section on transitioning pediatric patients to adult care， and discuss the optimal timing， multidisciplinary team composition， and implementation frameworks of the transition plan. These updates fully reflect the latest evidence and the development of clinical needs in the diagnosis and treatment of Wilson’s disease. This article gives an excerpt of the recommendations in the guidelines.

BACKGROUND:Studies have shown that there is a close relationship between dendritic spine plasticity and Alzheimer's disease,and that resistance or aerobic exercise has some efficacy in improving cognitive dysfunction,but the mechanism of action is unclear.OBJECTIVE:To investigate the effect of aerobic exercise or resistance exercise on dendritic spine plasticity in the hippocampal CA1 region of APP/PS1 transgenic mice.METHODS:Thirty 3-month-old male APP/PS1 mice were selected and randomly divided into three groups:a model group,a resistance exercise group,and an aerobic exercise group.The same litter of 3-month-old C57BL/6J mice were selected as a blank group.Mice in the resistance exercise group were subjected to ladder-climbing exercise and those in the aerobic exercise group were subjected to treadmill exercise for 12 weeks.At the end of the exercise intervention,the water maze experiment and the new arm of the Y maze were used to assess behavioral changes in mice.Hematoxylin-eosin staining,Nissl staining,Golgi staining,and electron microscopy were performed to observe neuronal morphology,Nissl bodies,dendritic spines,and ultrastructural changes in the synapses of the hippocampal region of the mouse brain.The protein expression levels of hippocampal amyloid-beta1-42,Ras,and Drebrin were measured using Western blot analysis.RESULTS AND CONCLUSION:Mice in the model group exhibited a prolonged escape latency over 5 consecutive days(P＜0.05,P＜0.01)and significantly fewer entries into the new arm of the Y maze(P＜0.01).Dendritic spine density in the CA1 region of the hippocampus,as well as Ras and Drebrin expression in the hippocampal tissues of mice in the model group,were lower than those in the normal group(P＜0.01),and amyloid-beta1-42 expression in the hippocampal tissues was higher in the model group compared with the normal group(P＜0.01).Mice in the resistance exercise group and the aerobic exercise group displayed a shortened escape latency over the same 5-day period(P＜0.05,P＜0.01)and showed a significantly greater number of entries into the new arm of the Y maze compared with the normal group(P＜0.01).Dendritic spine density in the CA1 region of the hippocampus,as well as Ras and Drebrin expression in the hippocampal tissues,were higher in both the resistance exercise group and the aerobic exercise group compared with the model group(P＜0.01).Amyloid-beta1-42 expression in the hippocampal tissue was lower in both exercise groups than in the model group(P＜0.01).To conclude,long-term regular aerobic or resistance exercise interventions can increase dendritic spine density and synaptic plasticity in the CA1 region of the hippocampus,enhancing spatial learning and memory abilities in a mouse model of Alzheimer's disease.These effects may be associated with increased expression of Ras and Drebrin proteins in the hippocampus.

The accuracy of orthodontic bracket bonding directly affects the treatment effect,and intelligent orthodontics is gradually advancing clinical practice toward precision.Mixed reality(MR),a new digital holographic imaging simulation technology,enables interactive scenarios between 3D data and the real world,allowing precise identification and localization of dental roots and jaw ana-tomical structures.This study constructs an oral visualization model via multimodal image fusion,establishes a virtual-real registra-tion algorithm combining target detection and point cloud registration for high-dynamic scenarios,and develops an MR-based intelli-gent auxiliary and teaching system for orthodontic bracket bonding.The system achieves clinical training and intraoperative naviga-tion for bracket positioning and bonding,accurately identifies dental root and jaw information,and is of significant importance for improving the precision,intelligence,and digitization of orthodontic clinical practice.

Objective:To investigate the clinical manifestations, pathological features, and genetic variant characteristics of children with glycogen storage disease type Ⅸa (GSD Ⅸa).Methods:A retrospective case series analysis was conducted to collected and analyzed the medical history, biochemical markers, liver ultrasound results, liver histopathological findings, genotypes, treatment regimens, and follow-up data of 4 pediatric patients diagnosed with GSD IXa in the Department of Infectious Diseases at Xiamen Children′s Hospital from January 2018 to May 2024. All patients were confirmed by genetic testing.Results:All 4 pediatric patients diagnosed with GSD Ⅸa were male. The ages of onset were 8 months, 2 years, 3 years and 3 months, 1 year and 5 months, respectively, with initial presentations including chronic diarrhea (Case 1), incidentally detected transaminase elevation during routine examinations (Cases 2 and 3), and delayed motor development (Case 4). Diagnosis was confirmed at ages 10 months, 3 years, 3 years 4 months and 1 year 6 months, respectively.At diagnosis, anthropometric parameters and biochemical profiles revealed:Height: 68 cm (< P3), 96 cm ( P25-50), 94 cm ( P3-10), and 94 cm ( P3-10).Weight: 7 kg (< P3), 17 kg ( P90-97), 14.4 kg ( P25-50), and 10.5 kg ( P25-50).Alanine aminotransferase: 299, 500, 271, and 313 U/L (reference range 0-40 U/L).Aspartate aminotransferase: 285, 543, 337 and 357 U/L (reference range 0-40 U/L).Fasting glucose: 2.80, 3.67, 2.98, and 3.66 mmol/L (reference range 3.90-6.10 mmol/L).Lactate: 4.3, 2.1, 1.3, and 2.6 mmol/L (reference range 0.5-2.2 mmol/L).Triglycerides: 5.22, 1.38, 1.32, and 1.88 mmol/L (reference range 0.56-1.70 mmol/L).Case 1 exhibited poor adherence to uncooked cornstarch therapy during initial treatment, with no significant improvement in biochemical parameters. Follow-up imaging at age 4 revealed hepatic adenoma. Subsequent improvement in therapeutic compliance led to biochemical normalization, reduced hepatic adenoma size, and growth parameters of 113 cm ( P10-25) and 26 kg ( P90-97) at 6 years 2 months. Cases 2-4 demonstrated biochemical improvement with regular uncooked cornstarch therapy and no evidence of hepatic adenoma.Liver histopathology in Cases 1-3 confirmed glycogen accumulation consistent with GSD, without cirrhotic changes. Genetic analysis identified PHKA2 variations in all cases: 2 missense variants, 1 frameshift variant and 1 nonsense variant. The c.2839dup and c.3267G>A variants represent novel pathogenic mutations. Conclusions:GSD Ⅸa in pediatric patients is predominantly characterized by hepatomegaly, hepatic dysfunction, and hypoglycemia. While uncooked cornstarch therapy typically yields favorable prognoses, a subset of patients may develop hepatic adenomas. Notably, children with hepatic adenoma exhibited younger age of onset, significant growth retardation, and more severe metabolic disturbances, suggesting that hepatic adenoma development may be closely linked to the severity of metabolic dysregulation.

Objective:To analyze the clinical characteristics of mannose phosphate isomerase-congenital disorders of glycosylation (MPI-CDG) and evaluated the outcomes following D-mannose treatment.Methods:This case-series study analyzed clinical manifestations, laboratory findings, imaging results, genetic data, and outcomes after D-mannose therapy in 5 children with MPI-CDG diagnosed at the Children′s Hospital of Fudan University between December 2014 and December 2024.Results:The age of onset ranged from 0.3 to 0.4 years in all 5 children, who initially presented with diarrhea and hypoglycemia. Associated manifestations included short stature (3 cases), anemia (3 cases), splenomegaly (3 cases), hepatomegaly (4 cases), elevated transaminases (4 cases), and hypoalbuminemia (4 cases). Liver pathology revealed hepatic fibrosis in 3 cases. Genetic testing identified 8 variants in the MPI gene, including 2 novel variants. Following D-mannose treatment, diarrhea and hypoglycemia resolved within 1-2 weeks in all children, with concurrent improvement in anemia. Notably except for Patient 1, who developed progressive splenomegaly, worsening hepatic fibrosis, and portal hypertension despite persistently normal transaminase and albumin levels, the other 4 children showed improvement in transaminase levels, resolution of hypoalbuminemia and amelioration of imaging abnormalities.Conclusions:MPI-CDG typically manifests in infancy with diarrhea and hypoglycemia, often accompanied by multi-system involvement. D-mannose treatment significantly improves metabolic abnormalities and most organ damages. However, close surveillance of liver status is warranted due to the risk of hepatic fibrosis progression in some cases.

The accuracy of orthodontic bracket bonding directly affects the treatment effect,and intelligent orthodontics is gradually advancing clinical practice toward precision.Mixed reality(MR),a new digital holographic imaging simulation technology,enables interactive scenarios between 3D data and the real world,allowing precise identification and localization of dental roots and jaw ana-tomical structures.This study constructs an oral visualization model via multimodal image fusion,establishes a virtual-real registra-tion algorithm combining target detection and point cloud registration for high-dynamic scenarios,and develops an MR-based intelli-gent auxiliary and teaching system for orthodontic bracket bonding.The system achieves clinical training and intraoperative naviga-tion for bracket positioning and bonding,accurately identifies dental root and jaw information,and is of significant importance for improving the precision,intelligence,and digitization of orthodontic clinical practice.

BACKGROUND:Studies have shown that there is a close relationship between dendritic spine plasticity and Alzheimer's disease,and that resistance or aerobic exercise has some efficacy in improving cognitive dysfunction,but the mechanism of action is unclear.OBJECTIVE:To investigate the effect of aerobic exercise or resistance exercise on dendritic spine plasticity in the hippocampal CA1 region of APP/PS1 transgenic mice.METHODS:Thirty 3-month-old male APP/PS1 mice were selected and randomly divided into three groups:a model group,a resistance exercise group,and an aerobic exercise group.The same litter of 3-month-old C57BL/6J mice were selected as a blank group.Mice in the resistance exercise group were subjected to ladder-climbing exercise and those in the aerobic exercise group were subjected to treadmill exercise for 12 weeks.At the end of the exercise intervention,the water maze experiment and the new arm of the Y maze were used to assess behavioral changes in mice.Hematoxylin-eosin staining,Nissl staining,Golgi staining,and electron microscopy were performed to observe neuronal morphology,Nissl bodies,dendritic spines,and ultrastructural changes in the synapses of the hippocampal region of the mouse brain.The protein expression levels of hippocampal amyloid-beta1-42,Ras,and Drebrin were measured using Western blot analysis.RESULTS AND CONCLUSION:Mice in the model group exhibited a prolonged escape latency over 5 consecutive days(P＜0.05,P＜0.01)and significantly fewer entries into the new arm of the Y maze(P＜0.01).Dendritic spine density in the CA1 region of the hippocampus,as well as Ras and Drebrin expression in the hippocampal tissues of mice in the model group,were lower than those in the normal group(P＜0.01),and amyloid-beta1-42 expression in the hippocampal tissues was higher in the model group compared with the normal group(P＜0.01).Mice in the resistance exercise group and the aerobic exercise group displayed a shortened escape latency over the same 5-day period(P＜0.05,P＜0.01)and showed a significantly greater number of entries into the new arm of the Y maze compared with the normal group(P＜0.01).Dendritic spine density in the CA1 region of the hippocampus,as well as Ras and Drebrin expression in the hippocampal tissues,were higher in both the resistance exercise group and the aerobic exercise group compared with the model group(P＜0.01).Amyloid-beta1-42 expression in the hippocampal tissue was lower in both exercise groups than in the model group(P＜0.01).To conclude,long-term regular aerobic or resistance exercise interventions can increase dendritic spine density and synaptic plasticity in the CA1 region of the hippocampus,enhancing spatial learning and memory abilities in a mouse model of Alzheimer's disease.These effects may be associated with increased expression of Ras and Drebrin proteins in the hippocampus.