Objective:To explore the genetic basis of a patient suspected for Loeys-Dietz syndrome (LDS).Methods:An adult male patient with aneurysmal dilation of the aortic root identified during the treatment for chronic myeloid leukemia at Anzhen Hospital of Capital Medical University in 2021 was enrolled as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and his family members and subjected to whole-exome sequencing (WES). Candidate variant was verified by bioinformatic analysis, with a focus on the genes associated with hereditary aortic aneurysms. Candidate variant was validated by Sanger sequencing. The online SpliceAI software was used for the prediction of protein function. The results, combined with information from public databases, were used to classify the pathogenicity of the candidate variant according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Ethics Committee of Beijing Anzhen Hospital (Ethics No. 2023163X).Results:Imaging analysis revealed that the patient had aneurysmal dilation of the aortic root. Based on his clinical features and past history, a provisional diagnosis of LDS was established. WES revealed that the patient had harbored a heterozygous splice site variant c. 206+ 2T>G in the SMAD3 gene (NM_005902). The variant was not reported in public databases and was predicted to be pathogenic by SpliceAI. Sanger sequencing showed that the variant was also present in the patients mother, sister, nephew, and daughter, but not in his father. Based on the guidelines from the ACMG, the variant was classified as likely pathogenic (PVS1+ PM2_Supporting). Conclusion:The heterozygous splice site variant c. 206+ 2T>G of the SMAD3 gene probably underlay the disease of this patient. The discovery has enriched the mutational spectrum of LDS, which may facilitate delineation of the genotype-phenotype correlation and provide a basis for further risk stratification and personalized treatment of LDS.

OBJECTIVE: To explore the genetic basis of a patient suspected for Loeys-Dietz syndrome (LDS). METHODS: A adult male patient with aneurysmal dilation of the aortic root identified during the treatment for chronic myeloid leukemia at Anzhen Hospital of Capital Medical University in 2021 was selected as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and his family members and subjected to whole-exome sequencing (WES). Candidate variant was verified by bioinformatic analysis, with a focus on the genes associated with hereditary aortic aneurysms. Candidate variant was validated by Sanger sequencing. The online SpliceAI software was used for the prediction of protein function. The results, combined with information from public databases, were used to classify the pathogenicity of the candidate variant according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Ethics Committee of Beijing Anzhen Hospital (Ethics No. 2023163X). RESULTS: Imaging analysis revealed that the patient had aneurysmal dilation of the aortic root. Based on his clinical features and past history, a provisional diagnosis of LDS was established. WES revealed that the patient had harbored a heterozygous splice site variant c.206+2T>G in the SMAD3 gene (NM_005902). The variant was not reported in public databases and was predicted to be pathogenic by SpliceAI. Sanger sequencing showed that the variant was also present in the proband's mother, sister, nephew, and daughter, but not in his father. Based on the guidelines from the ACMG, the variant was classified as likely pathogenic (PVS1+PM2_Supporting). CONCLUSION The heterozygous splice site variant c.206+2T>G of the SMAD3 gene probably underlay the disease in this patient. Above discovery has enriched the mutational spectrum of LDS, which may facilitate delineation of the genotype-phenotype correlation and provide a basis for further risk stratification and personalized treatment of LDS.
Adult ; Humans ; Male ; Exome Sequencing ; Loeys-Dietz Syndrome/genetics* ; Mutation ; Pedigree ; Smad3 Protein/genetics*

Objective:To explore the genetic basis of a patient suspected for Loeys-Dietz syndrome (LDS).Methods:An adult male patient with aneurysmal dilation of the aortic root identified during the treatment for chronic myeloid leukemia at Anzhen Hospital of Capital Medical University in 2021 was enrolled as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and his family members and subjected to whole-exome sequencing (WES). Candidate variant was verified by bioinformatic analysis, with a focus on the genes associated with hereditary aortic aneurysms. Candidate variant was validated by Sanger sequencing. The online SpliceAI software was used for the prediction of protein function. The results, combined with information from public databases, were used to classify the pathogenicity of the candidate variant according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Ethics Committee of Beijing Anzhen Hospital (Ethics No. 2023163X).Results:Imaging analysis revealed that the patient had aneurysmal dilation of the aortic root. Based on his clinical features and past history, a provisional diagnosis of LDS was established. WES revealed that the patient had harbored a heterozygous splice site variant c. 206+ 2T>G in the SMAD3 gene (NM_005902). The variant was not reported in public databases and was predicted to be pathogenic by SpliceAI. Sanger sequencing showed that the variant was also present in the patients mother, sister, nephew, and daughter, but not in his father. Based on the guidelines from the ACMG, the variant was classified as likely pathogenic (PVS1+ PM2_Supporting). Conclusion:The heterozygous splice site variant c. 206+ 2T>G of the SMAD3 gene probably underlay the disease of this patient. The discovery has enriched the mutational spectrum of LDS, which may facilitate delineation of the genotype-phenotype correlation and provide a basis for further risk stratification and personalized treatment of LDS.

Objective:To investigate the efficacy of the nomogram model based on multiparametric MRI combined with clinical features for differential diagnosis of benign and malignant breast imaging reporting and data system (BI-RADS) 4 lesions.Methods:This study was a cross-sectional study. Clinical and imaging data of 56 patients (66 lesions) with pathologically confirmed BI-RADS 4 breast lesions from January 2020 to June 2022 at Second Affiliated Hospital of Shantou University Medical College were retrospectively analyzed. The patients were all females aged 42 (17, 71) years old. All patients underwent the breast MRI, including T 1WI, T 2WI, diffusion-weighted imaging, diffusion kurtosis imaging (DKI), and dynamic-enhanced MRI (DCE-MRI), and the patient clinical characteristics, imaging characteristics as well as relevant MRI quantitative parameters were recorded. Comparisons of the indicators of benign and malignant BI-RADS 4 lesions were performed by sample t-test , Mann-Whitney U, or χ 2 test. The least absolute shrinkage and selection operator regression was utilized to further select indicators with statistically significant differences in univariate analyses, and finally, nomogram models were constructed and reclassified all the lesions. Results:Of the 66 lesions in 56 patients, 24 lesions were found in 24 malignant patients and 42 lesions in 32 benign patients. The differences in age, body mass index, and menopausal status between benign and malignant patients were statistically significant (all P<0.05); the differences in tumor longest diameter, type of lesion enhancement, time-single intensity curve type, mean diffusivity and mean kurtosis (MK) between benign and malignant lesions were statistically significant (all P<0.05). After feature selection, MK ( OR=27.952, 95% CI 1.301-600.348, P=0.033), age ( OR=1.140, 95%CI 1.040-1.249, P=0.005), and the type of lesion enhancement ( OR=0.045, 95%CI 0.006-0.316, P=0.005) were the independent influences in predicting BI-RADS 4 malignant lesions. Using this to construct a nomogram model, its area under the curve for predicting BI-RADS 4 malignant lesions was 0.946, and the accuracy of reclassifying 66 BI-RADS 4 lesions as benign versus malignant was 86.36% (57/66). Conclusion:The nomogram model constructed with MK from DKI parameters, the type of lesion enhancement from DCE-MRI, and age is valuable in diagnosing the benign and malignant nature of BI-RADS 4 lesions.

Objective:To investigate the value of multi-parameter MRI habitat imaging in differentiating human epidermal growth factor receptor 2 (HER2) expression in breast cancer.Methods:This study was cross-sectional. A retrospective analysis was conducted on the clinical and imaging data of 86 cases of primary invasive breast cancer confirmed by pathology at the Second Affiliated Hospital of Shantou University from August 2018 to July 2023. All patients were female, aged 33 to 74 (51±10) years. All patients underwent breast MRI examinations, including T 1WI, T 2WI, diffusion-weighted imaging and dynamic contrast-enhanced MRI. The fuzzy C-means clustering algorithm was applied to cluster analysis of the volume ratio of the extracellular extravascular space (V e), the rate constant (K ep), the volume transfer constant (K trans), and the apparent diffusion coefficient (ADC) for all lesions. Different habitat subregions were segmented based on breast cancer. Blood perfusion of the lesion was quantified through mean values of K trans and K ep, and cell proliferation was evaluated by the mean values of ADC and V e in each subregion. Additionally, the percentage of each subregion′s volume in relation to the total lesion volume was calculated. The Mann-Whitney U test was used to compare the differences in the volume percentages of various habitat subregions between different HER2 expression status. The diagnostic performance of statistically significant parameters in determining HER2 status was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Results:Among the 86 patients with invasive breast cancer, 27 were HER2 positive and 59 were HER2 negative. Among the HER2 negative patients, 37 had low and 22 had zero HER2 expression. The volume percentages of habitat subregions 1, 2, and 3 showed statistically significant differences between HER2 positive and HER2 negative patients ( Z=2.90, P=0.004; Z=-2.04, P=0.042; Z=-2.19, P=0.029), with AUC values of 0.696, 0.638, and 0.648, respectively, for predicting HER2 positive expression. The volume percentage of habitat subregion 2 showed a statistically significant difference between low and zero HER2 expression patients ( Z=2.85, P=0.004), with an AUC value of 0.724 for predicting low versus zero HER2 expression. Conclusions:The volume percentage of habitat subregion 1 effectively distinguishes HER2 status, and the volume percentage of habitat subregion 2 effectively distinguishes between low and zero HER2 expression patients. It has significant clinical implications for identifying potential candidates for HER2-targeted therapy.

Objective:To analyze the clinical efficacy and prognostic factors of comprehensive treatment for atypical teratoid / rhabdomyoma tumor (AT/RT).Methods:Clinical data of children diagnosed with AT/RT who underwent radiotherapy in Department of Oncology of Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine from November 2012 to September 2022 were retrospectively analyzed. Pearson Chi-square test or continuous-corrected Chi-square test or Fisher's exact probability method were used for inter-group comparison of categorical variables. Independent sample t-test or Wilcoxon rank-sum test were used for inter-group comparison of continuous variables. Kaplan-Meier method was used to calculate the 1-year and 2-year overall survival (OS) rate and progression free survival (PFS) rate. Univariate and multivariate Cox regression analyses were employed to determine relevant prognostic factors. Results:A total of 45 patients were included, with a male/female ratio of 1.65:1, including 27 children aged ≥3 years old. All patients received surgery and radiotherapy in which 39 patients received chemotherapy, 41 craniospinal irradiation (CSI), and 4 whole brain or focal radiation therapy. The median follow-up was 28 (13.5, 49) months. A total of 14 patients died after comprehensive treatment. The 1-year OS rate was 80.0% and the PFS rate was 71.1%. The 2-year OS rate was 75.5% and the PFS rate was 65.7%. Survival prognostic analysis showed negative imaging assessment after radiotherapy ( HR=0.087, 95% CI: 0.011-0.697, P=0.022) was a favorable factor for PFS. The primary tumor<4.8 cm ( HR=0.221, 95% CI: 0.052-0.935, P=0.040) and CSI ( HR=0.085, 95% CI: 0.011-0.651, P=0.018) were favorable factors for OS. In subgroup analysis, CSI also improved OS in children aged ≥3 years ( HR=0.014, 95% CI: 0-0.470, P=0.017), but there was no significant difference in PFS. In children without cerebrospinal fluid dissemination, negative radiographic results after radiotherapy ( HR=0.066, 95% CI: 0.009-0.481, P=0.007; HR=0.076, 95% CI: 0.008-0.695, P=0.024, respectively) and CSI (HR=0.105, 95% CI: 0.012-0.937, P=0.044; HR=0.054, 95% CI: 0.005-0.629, P=0.020, respectively) were favorable factors for PFS and OS in children, and the primary tumor<4.8 cm also suggested a longer OS ( HR=0.094, 95% CI: 0.013-0.690, P=0.020). Conclusions:Comprehensive treatment including radiotherapy improves clinical prognosis of children with AT/RT. Our study shows that negative imaging results after radiotherapy are associated with PFS improvement. The primary tumor<4.8 cm and CSI are favorable factors for OS. CSI is also a significantly positive prognostic factor in children aged ≥3 years and those without cerebrospinal fluid dissemination.

Objective:To explore whether anlotinib or bevacizumab has better efficacy in patients with recurrent glioblastoma.Methods:The clinical characteristics and treatment data of patients with recurrent glioblastoma admitted to Ren Ji Hospital,Shanghai Jiao Tong University School of Medicine,were collected retrospectively.All patients received maximal resection of the tumor combined with postoperative adjuvant radiotherapy and chemotherapy,and the recurrence was detected by head contrast-enhanced MRI.According to the choice of anti-vascular therapy,the patients were divided into anlotinib group and bevacizumab group.Survival curves were drawn to compare the overall survival time of the two groups of patients,and subgroup analysis was performed according to the basic information of the patients and whether they received temozolomide chemotherapy or radiotherapy after recurrence.Results:A total of 37 patients were enrolled in the study,19 in the anlotinib group and 18 in the bevacizumab group.The median overall survival time was 16.3 months,with 19.6 months in the anlotinib group and 12.8 months in the bevacizumab group.However,survival analysis showed that there was no significant difference in survival time between the anlotinib group and the bevacizumab group(P=0.88).Further subgroup analysis showed that there was no significant difference in survival time between the two groups in all subgroups.Conclusion:This study provided an initial indication of the efficacy of anlotinib in patients with recurrent glioblastoma and suggested that oral anlotinib may be a viable option for patients who were unable to tolerate bevacizumab or who had.

Objective:To explore whether anlotinib or bevacizumab has better efficacy in patients with recurrent glioblastoma.Methods:The clinical characteristics and treatment data of patients with recurrent glioblastoma admitted to Ren Ji Hospital,Shanghai Jiao Tong University School of Medicine,were collected retrospectively.All patients received maximal resection of the tumor combined with postoperative adjuvant radiotherapy and chemotherapy,and the recurrence was detected by head contrast-enhanced MRI.According to the choice of anti-vascular therapy,the patients were divided into anlotinib group and bevacizumab group.Survival curves were drawn to compare the overall survival time of the two groups of patients,and subgroup analysis was performed according to the basic information of the patients and whether they received temozolomide chemotherapy or radiotherapy after recurrence.Results:A total of 37 patients were enrolled in the study,19 in the anlotinib group and 18 in the bevacizumab group.The median overall survival time was 16.3 months,with 19.6 months in the anlotinib group and 12.8 months in the bevacizumab group.However,survival analysis showed that there was no significant difference in survival time between the anlotinib group and the bevacizumab group(P=0.88).Further subgroup analysis showed that there was no significant difference in survival time between the two groups in all subgroups.Conclusion:This study provided an initial indication of the efficacy of anlotinib in patients with recurrent glioblastoma and suggested that oral anlotinib may be a viable option for patients who were unable to tolerate bevacizumab or who had.

Objective:To investigate the clinic opathological features, treatment and prognosis of children newly diagnosed with ependymoma.Methods:Clinical data of 127 pediatric ependymoma (EPN) patients (0-16 years old) treated with tumor resection and postoperative radiotherapy at Xinhua Hospital Affiliated to Shanghai Jiao Tong University between 2001 and 2021 were retrospectively analyzed. Among them, 53 children were female and 74 were male. Local control (LR), event-free survival (EFS) and overall survival (OS) rates were analyzed by Kaplan-Meier method. The relationship between clinic opathological factors and clinical prognosis, and the effect of treatment on clinical prognosis of patients were analyzed by Cox proportional hazards model.Results:At a median follow-up time of 29 months (3-251 months), the 3-year OS and EFS rates were 89.5% and 71.5%, respectively. For patients undergoing incomplete resection followed by postoperative adjuvant radiotherapy, the 3-year LR, OS and EFS rates were 78.3%, 65.8% and 85.7%, respectively. A total of 43 children were aged <3 years old when diagnosed and 84 aged ≥3 years old. The interval time between surgery and radiotherapy in children aged <3 years old was 91 d, and 35.5 d in those aged ≥3 years old ( P<0.001). For patients <3 years old, the median EFS was 90 months when initiating radiotherapy within ≤70 d after surgery, compared to 43 months for those who initiated radiotherapy at >70 d after surgery ( P=0.053). According to fifth edition of the WHO classification of tumors of the central nervous system (WHO CNS5), 39 children were classified as posterior fossa ependymoma group A (PFA group). The OS and EFS rates in the PFA group were significantly less than those in other groups (3-year OS rate were 69.2% vs. 94.6%, P<0.001; 3-year EFS rate were 46.9% vs. 79.1%, P<0.001). In the PFA group, 12 patients received postoperative adjuvant chemotherapy, 14 did not receive chemotherapy, and whether chemotherapy was given was unknown in 13 cases. No significant differences were observed in OS and EFS between patients treated with and without chemotherapy ( P=0.260, P=0.730). Univariate Cox analysis showed that tumor location and WHO CNS5 molecular classification were significantly associated with EFS, and WHO CNS5 molecular classification was significantly correlated with OS. Multivariate Cox analysis showed that tumor location in the posterior fossa was an independent risk factor for EFS ( HR=2.72, 95% CI=1.1~6.71, P=0.03). Conclusions:Patients newly diagnosed with pediatric ependymoma can obtain favorable survival after surgery combined with postoperative adjuvant radiotherapy. Patients with residual tumors can achieve favorable LC and survival after postoperative adjuvant radiotherapy. Delaying of radiotherapy tends to lead to poor survival for patients aged <3 years old when diagnosed. Children in the PFA group obtain worse prognosis compared to their counterparts in other groups. The tumor location in the posterior fossa is an independent risk factor for pediatric ependymoma.

Humans ; Female ; Prevalence ; Breast Neoplasms ; Cancer Survivors ; Non-alcoholic Fatty Liver Disease ; Liver