Objective:To explore the phenotypic heterogeneity among patients harboring identical pathogenic variants in the dystrophin ( DMD) gene by analyzing clinical and imaging data from 7 pairs of male twins with dystrophinopathy. Methods:Clinical and laboratory data of 14 (7 pairs) male twins diagnosed with dystrophinopathy through genetic testing among 1 767 patients at Peking University First Hospital from January 2017 to October 2024 were collected. Eleven patients underwent thigh muscle magnetic resonance imaging (MRI), and muscle biopsies were performed in at least 1 case of each pair.Results:Among the 7 pairs of twin patients, 2 pairs had Duchenne muscular dystrophy, and 5 pairs had Becker muscular dystrophy. In terms of variant types, 4 pairs had in-frame deletions, while the remaining 3 pairs had duplication variants, frameshift variants, and nonsense variants, respectively. Clinically, 6 individuals had asymptomatic hypercreatine kinasemia, and 8 had varying degrees of limb weakness. Among the 5 pairs of symptomatic twins, there were differences in the degree of limb weakness. Four individuals showed no significant abnormalities in thigh muscle MRI, 7 showed fat infiltration mainly in the bilateral gluteus maximus and adductor magnus muscles, and 2 pairs of twins had obvious differences in the degree of fat infiltration in muscle MRI. Muscle biopsies revealed dystrophic or mild myopathic pathological changes, with 2 individuals showing severe loss of dystrophin, while the others had partial loss.Conclusions:Dystrophinopathy exhibits significant individual differences. Even among individuals with highly similar genetic background, clinical and imaging manifestations caused by the same pathogenic variant also vary.

Objective To investigate the effects of artesunate(Art)on the proliferation,apoptosis,and autophagy of nephroblastoma cell line(SK-NEP-1).Methods SK-NEP-1 cells were intervened with different concentrations of Art(0,10,20,40 and 80 μmol/L),and MTT method was applied to calculate the cell proliferation inhibition rate to screen the optimal intervention concentration;SK-NEP-1 cells were separated into control group,Art group,3-MA group(Art+autophagy inhibitor,3-methyladenine),and Rapa group(Art+autophagy activator rapamycin).EdU and flow cytometry were applied to detect cell proliferation and apoptosis,respectively;MDC staining was applied to detect autophagy in cells;the level of reactive oxygen species(ROS)in cells was detected by DCFH-DA fluorescent probe;the expression of proliferating cell nuclear antigen(PCNA),anti apoptotic factor B cell lym-phomatoma-2(Bcl-2),Bcl-2 associated X protein(Bax),microtubule junction protein 1 light chain 3 Ⅱ/3 Ⅰ(LC3 Ⅱ/LC3 Ⅰ),selective autophagy junction protein 1(p62),and benzyl chloride 1(Beclin-1)proteins in cells were detected by Western blot.Results Compared with 0 μmol/L Art,the proliferation inhibition rate of SK-NEP-1 cells was gradually increased after 10,20,40 and 80 μmol/L Art treatment(P＜0.05),and the IC50 value was 46.881 μmol/L,so 40 μmol/L Art was selected for follow-up experiments.Compared with the control group,the apoptosis rate,relative autophagy fluorescence intensity,ROS level,Bax,LC3 Ⅱ/LC3 Ⅰ,Beclin-1,PINK1,and Parkin protein expression levels of SK-NEP-1 cells in the Art group were obviously increased,the EdU positive cell rate,PCNA,Bcl-2,and P62 protein expression levels were obviously reduced(P＜0.05);The auto-phagy inhibitor 3-MA inhibited the promoting effect of Art on apoptosis and autophagy of nephroblastoma cells and inhibit proliferation(P＜0.05).Conclusions Art inhibits the proliferation of nephroblastoma cell line SK-NEP-1,and promotes autophagy and apoptosis.

Objective:To explore the phenotypic heterogeneity among patients harboring identical pathogenic variants in the dystrophin ( DMD) gene by analyzing clinical and imaging data from 7 pairs of male twins with dystrophinopathy. Methods:Clinical and laboratory data of 14 (7 pairs) male twins diagnosed with dystrophinopathy through genetic testing among 1 767 patients at Peking University First Hospital from January 2017 to October 2024 were collected. Eleven patients underwent thigh muscle magnetic resonance imaging (MRI), and muscle biopsies were performed in at least 1 case of each pair.Results:Among the 7 pairs of twin patients, 2 pairs had Duchenne muscular dystrophy, and 5 pairs had Becker muscular dystrophy. In terms of variant types, 4 pairs had in-frame deletions, while the remaining 3 pairs had duplication variants, frameshift variants, and nonsense variants, respectively. Clinically, 6 individuals had asymptomatic hypercreatine kinasemia, and 8 had varying degrees of limb weakness. Among the 5 pairs of symptomatic twins, there were differences in the degree of limb weakness. Four individuals showed no significant abnormalities in thigh muscle MRI, 7 showed fat infiltration mainly in the bilateral gluteus maximus and adductor magnus muscles, and 2 pairs of twins had obvious differences in the degree of fat infiltration in muscle MRI. Muscle biopsies revealed dystrophic or mild myopathic pathological changes, with 2 individuals showing severe loss of dystrophin, while the others had partial loss.Conclusions:Dystrophinopathy exhibits significant individual differences. Even among individuals with highly similar genetic background, clinical and imaging manifestations caused by the same pathogenic variant also vary.

Background::Thoracic aortic aneurysm (TAA) is a fatal cardiovascular disease, the pathogenesis of which has not yet been clarified. This study aimed to identify and validate the diagnostic markers of TAA to provide a strong theoretical basis for developing new methods to prevent and treat this disease.Methods::Gene expression profiles of the GSE9106, GSE26155, and GSE155468 datasets were acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the "limma" package in R. Least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), random forest, and binary logistic regression analyses were used to screen the diagnostic marker genes. Single-sample gene set enrichment analysis (ssGSEA) was used to estimate immune cell infiltration in TAA.Results::A total of 16 DEGs were identified. The enrichment and functional correlation analyses showed that DEGs were mainly associated with inflammatory response pathways and collagen-related diseases. Collagen type I alpha 1 chain ( COL1A1) and synaptotagmin like 2 ( SYTL2) were identified as diagnostic marker genes with a high diagnostic value for TAA. The expression of COL1A1 and SYTL2 was considerably higher in TAA vascular wall tissues than in the corresponding normal tissues, and there were significant differences in the infiltration of immune cells between TAA and normal vascular wall tissues. Additionally, COL1A1 and SYTL2 expression were associated with the infiltration of immune cells in the vascular wall tissue. Single-cell analysis showed that COL1A1 in TAA was mainly derived from fibroblasts and SYTL2 mainly from cluster of differentiation (CD)8 + T cells. In addition, single-cell analysis indicated that fibroblasts and CD8 + T cells in TAA were significantly higher than those in normal arterial wall tissue. Conclusions::COL1A1 and SYTL2 may serve as diagnostic marker genes for TAA. The upregulation of SYTL2 and COL1A1 may be involved in the inflammatory infiltration of the vessel wall and poor extracellular matrix remodeling, promoting the progression of TAA.

Objective:To explore the application value of preoperative serum vitamin A level in the prediction of benign or malignant pulmonary nodules.Methods:It was a retrospective cohort study. A total of 1 224 patients who underwent surgery for pulmonary nodules at the General Hospital of the People′s Liberation Army from January 2016 to December 2018 were consecutively included. The demographic information, postoperative pathological results, pulmonary CT findings and preoperative serum vitamin A test results were collected. The preoperative serum vitamin A levels of patients with lung cancer and benign pulmonary nodules were compared pairwise using the χ2 test. Logistic regression analysis was used to analyze the relevant factors for the occurrence of lung cancer and a stratified analysis was performed too. Prediction models for the benignity or malignancy of pulmonary nodules were constructed based on the results of multivariate logistic regression analysis. The efficacy of the models was evaluated, and the optimal preoperative prediction model was determined. The application value of preoperative serum vitamin A levels in predicting the benignity or malignancy of pulmonary nodules was then analyzed. Results:Of the 1 224 patients, postoperative pathology confirmed 1 044 cases with lung cancer and 180 cases with benign pulmonary nodules. The mean preoperative serum vitamin A level of patients with lung cancer was significantly lower than that in patients with benign pulmonary nodules (0.90 vs 1.06 μmol/L) ( Z=-3.493; P<0.001). Preoperative serum vitamin A level was a negative related factor for the occurrence of lung cancer ( OR=0.663, 95% CI: 0.484-0.914) ( P=0.011). In patients aged<60 years ( OR=0.623, 95% CI: 0.428-0.912), male ( OR=0.649, 95% CI: 0.438-0.976), with a body mass index≥24 kg/m 2 ( OR=0.634, 95% CI: 0.420-0.974), no family history of tumors ( OR=0.634, 95% CI: 0.440-0.923), no smoking history ( OR=0.619, 95% CI: 0.412-0.941), no drinking history ( OR=0.625, 95% CI: 0.424-0.933), with pulmonary nodules measuring 1-3 cm in diameter ( OR=0.643, 95% CI: 0.455-0.920), and with solid pulmonary nodules ( OR=0.681, 95% CI: 0.466-1.001), the preoperative serum vitamin A levels were significantly negatively correlated with the occurrence of lung cancer (all P<0.05). The prediction model incorporating preoperative serum vitamin A, CT characteristics of pulmonary nodules (nodule diameter, density), and clinical characteristics (age, gender) showed the best predictive efficacy for the benignity or malignancy of pulmonary nodules (the area under the curve was 0.792). Conclusions:Among patients receiving surgical treatment for pulmonary nodules, the preoperative serum vitamin A level of patients with lung cancer is lower than that of patients with benign pulmonary nodules. The preoperative serum vitamin A level is a negative associated factor for the occurrence of lung cancer. A combined model incorporating the preoperative serum vitamin A level provides a good prediction of benign or malignant pulmonary nodules.

Objective:To evaluate the clinical efficacy of metal braided stent deployed by fully protruding into the inferior vena cava for the treatment of iliac vein compression syndrome(IVCS).Methods:The clinical data of patients with IVCS treated with interwoven nitinol mesh stent protruding into the inferior vena cava and released from Jan 2018 to May 2021 in our center were retrospectively analyzed.Results:A total of 118 patients were included in this study. Among them, 7 cases were complicated with acute thrombosis, 3 cases were complicated with post thrombotic syndrome (PTS), and 108 cases were no more thrombotic iliac vein compression. The technical success rate was 100%, with an average of 2.03±0.77 stents implanted. Of the 23 ulcer patients, 18 ulcers healed after intervention, and the healing rate was 78.26%. The postoperative CEAP grade was significantly improved ( t=11.54, P<0.01), and the primary patency rate and second patency rate were 97.46% and 98.31% at 1 year after intervention. Conclusion:The fashion of fully protruding into inferior vena cava deployment in the treatment of iliac vein compressive disease has a high patency rate and satisfactory clinical efficacy.

Objective:To evaluate the application value of three-dimension digital subtraction angiography (3D-DSA) in the diagnosis and treatment of iliac vein compression syndrome (IVCS).Methods:A retrospective analysis was made on 171 patients with a tentative diagnosis of IVCS based on signs, symptoms, and finding of CTV or MRV, and iliac vein angiography. The diagnostic efficacy of MRV, 2D-DSA and 3D-DSA were analyzed. The imaging advantages of 3D-DSA in the diagnosis and treatment of IVCS were evaluated.Results:Ninty-three patients underwent MRV and 3D-DSA simultaneously, 101 patients had 2D-DSA and 3D-DSA simultaneously. 3D-DSA was taken as gold standard, the diagonotic sensitivity, specificity, Youden index of MRV was 75.61%, 72.73% and 0.48 respectively. The sensitivity, specificity, Youden index of 2D-DSA was 90.22%, 100% and 0.90 respectively. There are significant differences in the diagonotic sensitivity between MRV and 3D-DSA, 2D-DSA and 3D-DSA ( P<0.05). There is no significant difference in the diagonotic specificity between MRV and 3D-DSA, 2D-DSA and 3D-DSA ( P=1.000). In this study, we found that 3D-DSA has greater imaging evaluation advantages in preoperative evaluation, intraoperative guidance and immediate postoperative reexamination in the diagnosis and treatment of iliac vein disease. Conclusions:3D-DSA can improve the detection rate of IVCS, and has its advantage in imaging evaluation.

Otitis media is one of the common ear diseases, and its accurate diagnosis can prevent the deterioration of conductive hearing loss and avoid the overuse of antibiotics. At present, the diagnosis of otitis media mainly relies on the doctor's visual inspection based on the images fed back by the otoscope equipment. Due to the quality of otoscope equipment pictures and the doctor's diagnosis experience, this subjective examination has a relatively high rate of misdiagnosis. In response to this problem, this paper proposes the use of faster region convolutional neural networks to analyze clinically collected digital otoscope pictures. First, through image data enhancement and preprocessing, the number of samples in the clinical otoscope dataset was expanded. Then, according to the characteristics of the otoscope picture, the convolutional neural network was selected for feature extraction, and the feature pyramid network was added for multi-scale feature extraction to enhance the detection ability. Finally, a faster region convolutional neural network with anchor size optimization and hyperparameter adjustment was used for identification, and the effectiveness of the method was tested through a randomly selected test set. The results showed that the overall recognition accuracy of otoscope pictures in the test samples reached 91.43%. The above studies show that the proposed method effectively improves the accuracy of otoscope picture classification, and is expected to assist clinical diagnosis.
Computers ; Diagnosis, Computer-Assisted ; Humans ; Neural Networks, Computer ; Otitis Media/diagnosis*

Objective:To explore the clinical characteristics, treatment and prognosis of myeloid sarcoma(MS).Methods:From January 2010 to May 2019, clinical data were reviewed for 89 MS cases. Age, gender, site of onset, type, comorbid diseases, lymphatic characteristics and disease remission status were analyzed. And 1-year survival rates were explored for different treatments including whether or not chemotherapy, transplantation and using hypomethylated drugs(HMAs)for maintenance after transplantation.Results:Among them, 21 cases had the data of chromosome karyotypic analysis and next generation sequencing and 8 patients underwent allogeneic hematopoietic stem cell transplantation(allo-HSCT). The 1-year overall survival rates(OS)of primary MS, MS with intramedullary disease and MS relapse after leukemic remission were 16.0%, 37.5% and 36.9% respectively( P=0.013). The 1-year OS of local treatment(surgical resection, intrathecal injection and local radiotherapy), chemotherapy plus local treatment and chemotherapy plus allo-HSCT was 0, 28.1% and 72.9% respectively( P=0.003). After two courses of treatment, the 1-year OS of patients with complete and incomplete remissions were 34.9% and 10.0% respectively( P=0.008). Half(4/8)MS patients relapsed within 1 year after transplantation and had a short survival.Three patients received decitabine after HSCT and all of them survived for a long time. Conclusions:Chemotherapy plus HSCT is efficacious for MS. Decitabine maintenance treatment after transplantation may prolong recurrence-free survival. However, a larger sample size is required for further clinical verifications.

Objective To study the effect different concentrations of HDAC6 inhibitor tubacin on the proliferation,morphology and membrane surface ultrastructure of bone marrow mesenchymal stem cells(BMSCs).Methods Primary BMSCs were cultured.The P4 generation cells were taken for conducting the experiment.The different concentrations of tubacin were used to treat the cells fro 24 h.The cells survival rate was detected by MTT assay.The atomic force microscopy(AFM) was applied to observe the cellular morphology and surface ultramicrostructure and detect the mechanical property in different groups.Results The MTT results showed that low concentration of tubacin had the effect for promoting BMSC proliferation;the AFM results showed that compared with the control group,the height and width of BMSCs after treating by low concentration of tubacin,the membrane surface roughness was decreased and cellular hardness was increased.Conclusion Low concentration of tubacin can promote the BMSC proliferation,causes the changes of morphology and membrane surface ultramicrostructure,enhances the mechanical property and increases the cell implantation treatment efficiency.