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 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.

OBJECTIVES: To investigate the regulatory mechanism of aurora kinase B (AURKB) for promoting malignant phenotype of osteosarcoma cells. METHODS: HA-Vector or HA-AURKB was transfected in 293T cells to identify the molecules interacting with AURKB using immunoprecipitation combined with liquid chromatography-tandem mass spectrometry followed by verification with co-immunoprecipitation and Western blotting. In cultured osteosarcoma cells with lentivirus-mediated RNA interference of AURKB or DHX9 or their overexpression, the changes in cell proliferation, migration, and invasion activities were observed with EDU and Transwell assays. Mechanistic analysis was performed using Co-IP and in vivo ubiquitination experiments to detect the interaction between AURKB and DHX9 and the phosphorylation and ubiquitination levels of DHX9. Western blotting was used to detect the effect of AURKB and DHX9 on activation of nuclear factor-κB (NF-κB) signaling. RESULTS: AURKB was highly expressed in osteosarcoma cell lines, and in osteosarcoma 143B cells, AURKB silencing significantly reduced cell proliferation, migration and invasion abilities. Interactions between AURKB and DHX9 were detected, and they were both highly expressed in osteosarcoma tissues; silencing AURKB reduced the protein expression of DHX9, and AURKB overexpression increased DHX9 phosphorylation. Silencing AURKB did not significantly affect the transcription and translation of DHX9 but accelerated its degradation and ubiquitination. Overexpression of DHX9 effectively reversed the effects of AURKB silencing on IKBα protein and phosphorylated p65, promoted nuclear translocation of p65 to activate the NF-κB signaling pathway, and enhanced the proliferation, migration, and invasion abilities of cultured osteosarcoma cells. CONCLUSIONS AURKB overexpression promotes the malignant phenotype of osteosarcoma cells by activating the NF-κB signaling pathway via regulating DHX9.
Humans ; Osteosarcoma/genetics* ; Cell Proliferation ; NF-kappa B/metabolism* ; Signal Transduction ; Cell Line, Tumor ; Cell Movement ; DEAD-box RNA Helicases/genetics* ; Aurora Kinase B/genetics* ; Phenotype ; Bone Neoplasms/genetics* ; Neoplasm Invasiveness ; Phosphorylation ; Neoplasm Proteins

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.

Currently, the treatment strategy for iliac venous thromboembolic disease has evolved from early approaches such as simple anticoagulation therapy, surgical thrombectomy, and venous return improvement to encompass multiple minimally invasive modalities including pharmacologic thrombolysis, catheter-directed thrombolysis (CDT), and mechanical thrombectomy. These advancements have demonstrated enhanced therapeutic efficacy and safety profiles. With the diversification of treatment modalities, the therapeutic concepts for venous thromboembolism (VTE) continue to be updated, establishing higher standards for treatment outcomes and safety. This article explored recent progress in the management of iliac venous thromboembolic disease, aiming to clarify the roles and efficacy of various treatment approaches in clinical practice while providing evidence-based treatment recommendation for clinicians. We anticipated further standardization of diagnostic and therapeutic protocols, along with increased emphasis on preventive measures, to safeguard vascular health in the general population.

Objective:To investigate the application value of serum fibroblast growth factor 21 (FGF21) levels in assessing disease status in patients with liver cancer.Methods:A cross-sectional study was conducted involving 157 hospitalized patients who received treatment at the Department of Infectious Disease, The First Hospital of Jiaxing between July 2020 and August 2021 (54 patients with liver cancer and 103 patients with chronic liver disease). General patient data were collected, and serum FGF21 levels were measured using the enzyme-linked immunosorbent assay. Pearson correlation analysis was performed to investigate the correlation between FGF21 levels and various indicators. Logistic regression analysis was performed to identify risk factors associated with the severity of liver cancer. Receiver operating characteristic curve analysis was conducted to evaluate the predictive value of FGF21 levels for liver cancer.Results:Serum FGF21 levels differed significantly between the liver cancer and chronic liver disease groups [399.91 (293.05, 572.65) ng/L vs. 174.16 (105.39, 255.16) ng/L, Z = 7.32, P < 0.001). Pearson correlation analysis indicated that FGF21 levels were positively correlated with sex, age, smoking, alcohol consumption, fasting blood glucose, total bilirubin, and prothrombin time (all P < 0.05). Logistic regression analysis revealed that FGF21 is an independent risk factor for liver cancer ( OR = 1.102, P < 0.001). According to the receiver operating characteristic curve, the area under the curve for FGF21 levels was 0.856, with an optimal cutoff value of 274.99 ng/L. This cutoff value demonstrated a sensitivity of 0.833 and a specificity of 0.796 for predicting liver cancer. Conclusion:In patients with liver cancer, elevated levels of FGF21 can be observed even when fasting blood glucose is normal, indicating its potential as a predictor for the occurrence of liver cancer. Furthermore, increased FGF21 levels are an independent risk factor for the development of liver cancer.

Objective:To investigate the application value of serum fibroblast growth factor 21 (FGF21) levels in assessing disease status in patients with liver cancer.Methods:A cross-sectional study was conducted involving 157 hospitalized patients who received treatment at the Department of Infectious Disease, The First Hospital of Jiaxing between July 2020 and August 2021 (54 patients with liver cancer and 103 patients with chronic liver disease). General patient data were collected, and serum FGF21 levels were measured using the enzyme-linked immunosorbent assay. Pearson correlation analysis was performed to investigate the correlation between FGF21 levels and various indicators. Logistic regression analysis was performed to identify risk factors associated with the severity of liver cancer. Receiver operating characteristic curve analysis was conducted to evaluate the predictive value of FGF21 levels for liver cancer.Results:Serum FGF21 levels differed significantly between the liver cancer and chronic liver disease groups [399.91 (293.05, 572.65) ng/L vs. 174.16 (105.39, 255.16) ng/L, Z = 7.32, P < 0.001). Pearson correlation analysis indicated that FGF21 levels were positively correlated with sex, age, smoking, alcohol consumption, fasting blood glucose, total bilirubin, and prothrombin time (all P < 0.05). Logistic regression analysis revealed that FGF21 is an independent risk factor for liver cancer ( OR = 1.102, P < 0.001). According to the receiver operating characteristic curve, the area under the curve for FGF21 levels was 0.856, with an optimal cutoff value of 274.99 ng/L. This cutoff value demonstrated a sensitivity of 0.833 and a specificity of 0.796 for predicting liver cancer. Conclusion:In patients with liver cancer, elevated levels of FGF21 can be observed even when fasting blood glucose is normal, indicating its potential as a predictor for the occurrence of liver cancer. Furthermore, increased FGF21 levels are an independent risk factor for the development of liver cancer.

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 investigate the efficacy and influencing factors of allo-HSCT in the treatment of MDS patients with ASXL1+.Methods The second-generation sequencing technique was used to detect 22 gene mutations in 247 newly diagnosed MDS patients in our hospital.The patients were divided into chemotherapy group and transplant group according to treatment style.The differences of OS and PFS between the two groups were compared,and the influencing factors of prognosis of transplant patients were analyzed.Results ASXL1+ was detected in 75 patients(30.36%),with a median mutation ratio of 42.93(18.10,58.39)%,10 received supportive treatment,43 received demethylation therapy or demethylation combined with pre-excitation therapy,and 22 received allo-HSCT.2-year PFS rate and OS rate of transplantation group were significantly higher than that of chemotherapy group(P<0.05).The 2-year OS rate in the low ASXL1 mutation load group(VAF≤42.93%)was significantly higher than that in the high ASXL1 mutation load group(VAF>42.93%)(P<0.05).In the context of allo-HSCT in patients with ASXL1+,2-year OS and PFS rates were significantly reduced in patients with RUNX1+ or ASXL1+(P<0.05);Multivariate analysis showed that high mutation load of ASXL1 or U2AF1+ were independent risk factors for OS in transplant patient(P<0.05).U2AF1+ were the risk factors for PFS(P<0.05).Conclusion allo-HSCT significantly improved the prognosis of patients with ASXL1+ MDS.High ASXL1 mutation load or U2AF1+ were independent risk factors affecting the outcome of allo-HSCT.

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.