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.

Objective To observe the correlations between left atrial myocardial strain and left ventricular function in children with Duchenne muscular dystrophy(DMD).Methods Fifty-one DMD children(DMD group)and 42 healthy one(control group)were prospectively enrolled.The parameters of routine ultrasound and three-dimensional speckle-tracking echocardiography(3D-STE)were compared between groups,and the correlations between left atrial strain parameters and left ventricular function parameters were analyzed.Results The mitral annular lateral wall velocity(e'),left ventricular ejection fraction(LVEF),left atrial ejection fraction(LAEF),left atrioventricular coupling index(LACI),left ventricular global longitudinal strain(LVGLS),left atrial strain during reservoir phase(LASr)and left atrial strain during conduit phase(LAScd)were all lower,while mitral early diastolic peak flow velocity/e'(E/e'),left atrial stiffness index(LASI)and left atrial filling index(LAFI)were higher in DMD group than those in control group(all P＜0.05).In DMD group,LAEF,LASr and LAScd were moderately positively correlated with LVGLS(r=0.409,0.437,0.440,all P＜0.05),LAFI and LASI were weakly negatively correlated with LVGLS(r=-0.207,-0.223,both P＜0.05),while LASr was moderately positively correlated with e'(r=0.419,P＜0.05).Conclusion The left atrial myocardial strain was correlated with left ventricular systolic and diastolic function in DMD children.

As orthodontic treatment improves malocclusion and enhances oral health quality,the number of orthodontic patients is steadily increasing.However,a lack of understanding of periodontal inflammation and the health of periodontal supporting tissues during orthodontic treatment can lead to alveolar bone destruction and resorption.This,in turn,results in periodontal hard tissue-related com-plications such as bone fenestration,bone dehiscence,abnormal interradicular distance,and tooth mobility or loss.Currently,these complications present a significant challenge in orthodontic practice.This paper provides a comprehensive overview of common perio-dontal hard tissue-related complications during orthodontic treatment,along with clinical prevention and management strategies.A typi-cal case of multidisciplinary periodontal treatment is also presented,addressing alveolar bone resorption and tooth mobility in the upper anterior teeth caused by improper orthodontic treatment.This report aims to offer valuable reference for clinicians.

The research on the mechanism of Chinese materia medica in the treatment of viral pneumonia (VP) is mainly based on the monomer components of Chinese materia medica and TCM compounds. Among them, the monomer components are mainly polyphenols, flavonoids and anthraquinones, which have anti-inflammatory, antiviral, immunomodulatory and antioxidant pharmacological effects. The efficacy of TCM compounds is mainly based on clearing heat, and it has the functions of removing phlegm, removing blood stasis, removing dampness, moistening lung and so on. The intervention of Chinese materia medica in VP mainly involves NF-κB, MAPK, JAK/STAT, PI3K/Akt and other signaling pathways. The mechanism includes regulating oxidative stress, apoptosis, regulating immune function, inhibiting inflammatory response, etc., which can reduce the pathological damage of inflammatory cell infiltration and edema in lung tissue, and achieve the protective effect on lung tissue. The current research models exhibit unclear patterns of syndrome differentiation, and the mechanisms of Chinese materia medica involving multiple targets and pathways are poorly understood. Future research should integrate disease-syndrome combination models to further explore the mechanisms by which TCM regulates multiple targets and pathways, thereby providing insights and methodologies for the treatment of viral pneumonia with Chinese materia medica.

Clinical management of atopic dermatitis (AD) is challenged by its susceptibility to recurrence, side effects, and high costs. We found that Portulaca oleracea L.-derived nanovesicles (PDNV) exert anti-inflammatory effects by modulating macrophage M1/M2 polarization. These effects were achieved through pathways including inhibition of nuclear factor-κB (NF-κB) and stimulator of interferon genes (STING) protein expression in diseased tissues, demonstrating their potential to ameliorate AD symptoms. To increase the transdermal permeation of PDNV, dissolvable microneedles composed primarily of hyaluronic acid (HA) were developed as an adjunctive means of delivery. Meanwhile, polysaccharides of Portulaca oleracea L., which were synergistic with PDNV, were used as microneedle constituent materials to enhance the mechanical properties and physical stability of HA. This new means of delivery significantly improves the treatment of AD and also provides new options for the efficient utilization of plant extracellular vesicles and the treatment of AD. In addition, transcriptomic analysis of PDNV showed that the mRNAs of Portulaca oleracea L. are closest to those of ferns, which may shed light on related evolutionary and plant species identification studies.

Liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist approved for diabetes and obesity, has shown significant potential in treating metabolic dysfunction-associated steatotic liver disease (MASLD). However, its systematic molecular regulation and mechanisms remain underexplored. In this study, a mouse model of MASLD was developed using a high-fat diet (HFD), followed by Lira administration. Proteomics and glycoproteomics were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS), while potential molecular target analysis was conducted via quantitative real-time polymerase chain reaction (qPCR) and Western blotting. Our results revealed that Lira treatment significantly reduced liver weight and serum markers, including alanine aminotransferase (ALT) and others, with glycosylation changes playing a more significant role than overall protein expression. The glycoproteome identified 255 independent glycosylation sites, emphasizing the impact of Lira on amino acid, carbohydrate metabolism, and ferroptosis. Simultaneously, proteomic analysis highlighted its effects on lipid metabolism and fibrosis pathways. 21 signature molecules, including 7 proteins and 14 N-glycosylation sites (N-glycosites), were identified as potential targets. A Lira hydrogel formulation (Lira@fibrin (Fib) Gel) was developed to extend drug dosing intervals, offering enhanced therapeutic efficacy in managing chronic metabolic diseases. Our study demonstrated the importance of glycosylation regulation in the therapeutic effects of Lira on MASLD, identifying potential molecular targets and advancing its clinical application for MASLD treatment.

Objective To explore the effect of exenatide on oxidative stress in the hypothalamus of diabetes mice and its potential mechanism.Methods After one week of adaptive feeding,C57BL/6J mice were randomly divided into the CON group(normal chaw diet),the T2DM group(high-fat diet,HFD),and the T2DM+Exe group(HFD+exenatide).After 8 weeks of HFD,mice in the T2DM+Exe group were intraperitoneally injected with exenatide[24 nmol/(kg·d)]for 8 weeks.The weight and glucose and lipid metabolism levels of the mice were measured,and the levels of inflammatory and adipokine factors in mice were detected using the ELISA method.Western Blot was used to detect the expression of melanocortin receptor-4(MC4R)and proopiomelanocor-tin(POMC)in the hypothalamus.Hypothalamic mitochondria were extracted,and the content of mitochondrial reactive oxygen species(ROS)was measured using a flow cytometer.The content of malondialdehyde(MDA)and the activities of superoxide dismutase(SOD)in the mitochondria were detected using assay kits.Changes in the ultrastructure of mitochondria were observed using a transmission electron microscope.In vitro experiments,pal-mitic acid(PA)and exenatide were used to treat hypothalamic GT1-7 cells,and short hairpin RNA(shRNA)was used to silence the melanocortin 4 receptor(MC4R),and observe the cellular oxidative stress and lipid deposition.Results Compared with the CON group,the T2DM group mice showed a significant increase in glucose and lipid metabolism indicators,pro-inflammatory factors,and adipose factor levels(P<0.05),the expression of MC4R and POMC proteins in the hypothalamus were decreased(P<0.05),and the mitochondrial ROS and MDA content in the hypothalamus significantly were increased(P<0.05),while SOD and CAT activities were decreased(P<0.05).Mitochondrial morphology was abnormal.After intervention with exenatide,the above indicators were signifi-cantly improved.After inhibiting MC4R expression in vitro experiments,compared with the intervention group with exenatide,the ROS and MDA content was significantly increased(P<0.05),SOD activity was decreased(P<0.05),and lipid deposition occurred in the cells.Conclusions Exenatide exhibits a protective effect on hypotha-lamic oxidative stress injury in diabetic mice,and this mechanism may be associated with the upregulation of MC4R expression.

Objective:To compare the effects of early orthodontic intervention and conventional sequential periodontal-orthodontic treatment to periodontal health in patients with stage Ⅳ periodontitis.Methods:A total of 30 patients with stage Ⅳ periodontitis, who underwent combined periodontal and orthodontic therapies at the Department of Periodontology, the Second Affiliated Hospital of Zhejiang University School of Medicine, from January 2018 to August 2024, were included. Patients who underwent early orthodontic intervention were initiated simultaneously or within one month after supragingival scaling and subgingival root planning ( n=15). While patients in control group accomplished supragingival scaling, subgingival root planning, and corresponding periodontal surgeries to achieve inflammation control before starting orthodontic treatment ( n=15). Periodontal parameters, including clinical attachment loss (CAL), probing depth (PD), and bleeding on probing (+) % [BOP (+) %], were measured at baseline, one year after orthodontic treatment, and at the end of combined periodontal-orthodontic therapy respectively. Improvements in periodontal parameters and differences in tooth loss between the two groups were compared. Results:After receiving combined periodontal-orthodontic treatment, the CAL of the early orthodontic intervention group significantly decreased from (4.39±0.90) mm before treatment to (2.41±0.35) mm at the end of treatment ( t=7.92, P<0.001). Similarly, the PD significantly reduced from (4.20±1.04) mm before treatment to (2.20±0.38) mm at the end of treatment ( t=7.01, P<0.001). The BOP(+)% also showed a significant improvement, decreasing from 89.29% (68.00%, 100.00%) before treatment to 13.04% (7.14%, 17.86%) at the end of treatment ( Z=-3.41, P<0.001). There were no statistically significant differences between the early orthodontic intervention group and control group in terms of baseline mean CAL, mean PD, and BOP(+)% ( t=1.30, P=0.205; t=1.28, P=0.212; Z=0.58, P=0.559). Furthermore, the improvements in CAL and PD between the two groups were not significantly different compared to baseline ( Z=-1.10, P=0.272; Z=-0.93, P=0.351). However, the number of missing teeth was significantly lower in the early orthodontic intervention group than in the control group (χ2=3.96, P=0.047). The duration of combined periodontal-orthodontic treatment in the early orthodontic intervention group was [33.13 (23.37, 36.20) months], which was significantly shorter than that in the control group [37.47 (32.33, 50.90) months] ( Z=2.07, P=0.037). Conclusions:Both early orthodontic intervention and conventional periodontal-orthodontic treatment significantly improved CAL, PD, and BOP(+)% in stage Ⅳ periodontitis patients. Early orthodontic intervention contributed to the preservation of natural teeth and shortened the treatment duration of stage Ⅳ periodontitis.

Multiple myeloma(MM)is a prevalent malignant tumor.Recent years,the efficacy of imaging diagnosis of MM progressively enhanced,and the application of radiomics had garnered increasing attention.The progresses of radiomics researches in multiple myeloma were reviewed in this article.