Objective To explore the clinical, radiological features and gene mutation of GALC gene in one child with globoid cell leukodystrophy (Krabbe disease). Methods The clinical and radiological data of a patient diagnosed with Krabbe disease through next-generation sequencing were retrospectively analyzed. Sanger sequencing was used to confirm the results. Results The patient was late infantile form with main manifestations of progressive psychomotor regression and convulsion. Brain MRI showed symmetric long T1 and long T2 signal changes in the white matter next to lateral ventricle angle, posterior limb of internal capsule, and the ministry of corpus callosum. The patient was found to have compound heterozygous mutations of c.1832T>C in exon 15 and c.979T>G in exon 9, which resulted in amino acid changes of p.L611S and p.F327V, respectively. Sanger sequencing results showed that the two heterozygous mutations were correspondingly inherited from his mother and father. Conclusions Next-generation sequencing technology is a useful tool for the detection of GALC gene mutation, which is valuable for definite diagnosis and differential diagnosis of Krabbe disease in clinical practice.

0.05).TNF-? mRNA in the intervenient group was significantly decreased to that of the control group(P

Objective: To evaluate the diagnostic value of a histologic scoring system in congenital biliary atresia and its prognostic relevance. Methods: From January 2017 to June 2018 at Children′s Hospital of Fudan University, 172 wedge liver biopsy specimens were obtained from infants with neonatal cholestasis [119 patients with congenital biliary atresia (CBA) and 53 patients with non-obstructive cholestasis as control]. A pathologist, single-blinded to the final diagnosis, made the histological diagnosis individually based on an 8-feature (portal ductal proliferation, bile duct reaction, bile plugs in portal ductules, liver fibrosis, edema in portal region, cholestasis, inflammatory cells infiltration in portal region, and ductal plate malformation), 21-point scoring system. Results: The main pathologic changes of biliary atresia were hepatocyte cholestasis, hyperplasia of bile ducts, fibrosis and infiltration of inflammatory cells in the portal area. There were significant difference in the degree of portal edema, bile duct hyperplasia and fibrosis between two groups (P<0.01). In addition, there were characteristic bile duct thrombosis in 97.5%(116/119) of the cases and abnormal development of bile duct plate in 9.2%(11/119) of the cases. Compared with non-CBA infant cholestasis group, the difference was statistically significant (P<0.05). The scoring system has high sensitivity, specificity (both 94.1%) and accuracy (94.3%) in the diagnosis of CBA. A score equal to or more than 11 points supported a diagnosis of CBA; whereas a score less than 11 points might suggest cholestasis. The degree of hepatic fibrosis and ductal plate malformation were related to prognosis. Conclusions The liver pathology scoring system (8-feature, 21-point) is more accurate in diagnosing CBA than previous methods, which may guide the clinicopathological diagnosis. This histological scoring system also helps to assess the prognosis of CBA.

Objective: To analyze the clinicopathologic characteristics of poorly-differentiated chordoma with INI1 loss in children and to discuss the differential diagnosis. Methods: The clinical, radiological, histopathological profiles and molecular pathologic characteristics of two pediatric poorly differentiated chordoma cases with INI1 loss were reviewed. Results: The patients were a girl and a boy. Both lesions involved the slope. Both patients were presented with progressive muscle weakness or neck pain. Radiological examination showed clivus bone destruction and compression of the brain stem and cervical spinal cord. Histologically, the tumor cells lacked typical organization and were associated with inflammatory cells infiltration. On high power field, the tumor cells were ovoid or fusiform with prominent atypia, vacuolated nuclei and prominent nucleoli. By immunohistochemistry, the tumor cells expressed cytokeratin, epithelial membrane antigen, brachyury and were negative for INI1. In both cases, INI1 gene deletion was detected by FISH. Conclusions Poorly-differentiated chordoma with INI1 loss mainly occurs in children. The morphology is different from classical chordoma.INI1 gene deletion is detectable by FISH. It can be distinguished from atypical teratoid/rhabdoid tumors and other neoplasms by the identification of nuclear brachyury expression. The loss of INI1 expression in poorly-differentiated chordoma might be associated with a poorly-differentiated morphology and an adverse prognosis.

Objective:To verify the protective effect of terazosin on cognitive function of rats after whole-brain irradiation (WBI) and to investigate its mechanism.Methods:A total of 64 1-month-old male SD rats were randomly divided into the untreated control group, terazosin group, irradiation group and irradiation plus terazosin group (combination group). WBI was administered at a single dose of 20 Gy in the irradiation and combination groups. The open field test and the Morris water maze (MWM) test were used to evaluate the effect of terazosin on cognitive function after WBI.Starting from the three aspects of juvenile neuron apoptosis, neurogenesis disorderand microglia activation, the possible cellular mechanism wasassayed by double-label immunofluorescence staining for BrdU (bromodeoxyuridine) / NeuN, DCX(Doublecortin) / Caspase-3 and single-label immunofluorescence staining for Iba-1 (ionized calcium binding adaptor molecule-1).Results:Terazosin intervention improved the short-term memory retention of irradiated rats ( P=0.032). After terazosin treatment, the number of DCX + cells in the combination groupwas increased by approximately 35% compared with that in the irradiation group ( P=0.038). The number of BrdU +/NeuN + cells in the combination group was increased by approximately 15% than that in the irradiation group ( P>0.05). The number of Iba-1 + cells in the irradiation plus terazosin group was decreased by 49% compared with that in the irradiation group ( P=0.036). Conclusion:Terazosin may reduce the hippocampal juvenile neuron loss and inhibit neuroinflammation via microglia activation, which can alleviate WBI-induced cognitive dysfunction to a certain extent.

Objective To investigate the clinicopathological features, diagnosis, differential diagnosis, treatment and prognosis of pediatric alveolar rhabdomyosarcoma (ARMS). Methods The clinical and pathological data of 25 pediatric ARMS from 2008 to 2018 in Children′s Hospital of Fudan University were collected. This histomorphology was assessed, and FOXO1 gene rearrangement was detected with FISH. The treatment details and outcome were analyzed. Results There were 13 males and 12 females, with ages range from 19 days to 14 years (median 6 years, mean 6.2 years). The ARMS were located in the limbs (13 cases), head and neck (4 cases), trunk (3 cases), abdominal cavity (3 cases), scrotum (1 case) and perianal region (1 case). The ARMS were classified histologically as classic group (18 cases), solid group (5 cases) and embryonic?alveolar mixed group (2 cases). The typical pathological characteristics were small dark round cells arranged in solid, glandular and papillary patterns. The tumor cells expressed ALK (D5F3) (21/25, 84.0%), muscle origin DES (23/25, 92.0%), myogenin (22/25, 88.0%), MYOD1 (19/25, 76.0%), and in some cases they also expressed neurogenic marker Syn (6/25, 24.0%). FOXO1 gene rearrangement was detected by FISH in 24/25 cases (96.0%). Conclusion Pediatric ARMS is rare and has unique clinicopathological characteristics, and needs to be differentiated from other common small round cell malignancies in children. ALK, DES, myogenin, MYOD1 immunohistochemistry and FOXO1 gene rearrangement are valuable aid in the diagnosis of ARMS.

Objective To evaluate the diagnostic value of a histologic scoring system in congenital biliary atresia and its prognostic relevance. Methods From January 2017 to June 2018 at Children′s Hospital of Fudan University, 172 wedge liver biopsy specimens were obtained from infants with neonatal cholestasis [119 patients with congenital biliary atresia (CBA) and 53 patients with non?obstructive cholestasis as control]. A pathologist, single?blinded to the final diagnosis, made the histological diagnosis individually based on an 8?feature (portal ductal proliferation, bile duct reaction, bile plugs in portal ductules, liver fibrosis, edema in portal region, cholestasis, inflammatory cells infiltration in portal region, and ductal plate malformation), 21?point scoring system. Results The main pathologic changes of biliary atresia were hepatocyte cholestasis, hyperplasia of bile ducts, fibrosis and infiltration of inflammatory cells in the portal area. There were significant difference in the degree of portal edema, bile duct hyperplasia and fibrosis between two groups (P<0.01). In addition, there were characteristic bile duct thrombosis in 97.5%(116/119) of the cases and abnormal development of bile duct plate in 9.2%(11/119) of the cases. Compared with non?CBA infant cholestasis group, the difference was statistically significant (P<0.05). The scoring system has high sensitivity, specificity(both 94.1%) and accuracy(94.3%) in the diagnosis of CBA. A score equal to or more than 11 points supported a diagnosis of CBA; whereas a score less than 11 points might suggest cholestasis. The degree of hepatic fibrosis and ductal plate malformation were related to prognosis. Conclusions The liver pathology scoring system (8?feature, 21?point) is more accurate in diagnosing CBA than previous methods, which may guide the clinicopathological diagnosis. This histological scoring system also helps to assess the prognosis of CBA.

Objective:To evaluate the effects of different imaging frequencies and matching strategies of cone-beam computed tomography (CBCT) on dose-volume parameters in target and organs at risk (OAR) during image-guided radiotherapy for prostate cancer.Methods:A total of 561 sets of CBCT images from 21 patients treated with radical prostate radiotherapy who were admitted to Peking University First Hospital from June 2022 to May 2023 were retrospectively analyzed. All patients received volumetric intensity modulated arc therapy (VMAT) at a prescribed dose of 70 Gy divided into 25 times, 2.8 Gy per time. Clinical target volume (CTV) and OAR were delineated by the same oncologist on each CBCT image. The planned CT (pCT) was rigorously registered to CBCT after calibration of positioning errors according to different image guidance modes and frequencies, and CT values and structures were propagated to CBCT through deformable image registration (DIR). The daily dose was mapped to pCT according to the deformation vector field (DVF) for dose accumulation. The actual cumulative dose of daily online CBCT validation was compared with the weekly CBCT validation regimen (days 1, 2, 3, 6, 11, 16 and 21 online imaging). The dosimetric comparison was also made between bone-based matching and soft tissue-based matching (after automatic bone-based matching, manual prostate-based matching was performed and fine-tuning was made regarding the anterior wall of rectum). Wilcoxon signed rank-sum test was utilized to analyze dose-volume parameters between planned and cumulative doses that exhibited non-normal distribution, while paired t-test was employed for assessing shift values and average dose parameters that demonstrated normal distribution. Results:Compared with daily CBCT image guidance, the CTV_D 98% in weekly CBCT was significantly reduced [(69.08±1.58) vs. (65.24±3.64) Gy, P<0.001]. The CTV_D 98% of bone-based matching was (69.27±2.14) Gy, but the high-dose volume of the rectum were significantly increased: V 60 Gy was 3.18%±3.10%, V 65 Gy was 0.77%±1.23%. The target area coverage using soft tissue-based matching is sufficient, with a CTV_D 98% of (69.08±1.58) Gy. And the percentage volume of high-dose volume of the rectum was significantly reduced, with V 60 Gy being 2.02%±2.42% and V 65 Gy being 0.34%±0.68%. Conclusions:In prostate cancer patients undergoing moderately-fractionated radiotherapy, daily CBCT image guidance demonstrates superior target coverage compared to a weekly scheme. Soft tissue-based matching, which is automatic bone-based matching followed by manual soft tissue-based matching and fine-tuning according to the anterior rectal wall, offers better rectal protection while maintaining target coverage.

Objective:To compare the efficacy and safety of standard treatment with or without adjuvant chemotherapy in patients with highly malignant non-metastatic prostate cancer.Methods:In this prospective non-randomized controlled study, consecutive non-metastatic prostate cancer patients with pathologically proven Gleason score of 9-10 or Gleason score of 5 admitted to Peking University First Hospital were enrolled. Four to six cycles of chemotherapy using docetaxel ± carboplatin regimen were added or not after standard radical therapy. The primary end point was 5-year event-free survival (EFS), and the secondary end points were distant metastasis-free survival (MFS), overall survival (OS), and treatment-related adverse events. The survival curve was drawn by Kaplan-Meier method. The differences between two groups were analyzed by log-rank test.Results:A total of 176 patients were consecutively enrolled from November 2019 to January 2022 of which 138 patients received only standard radical therapy (control group), and 38 patients received adjuvant chemotherapy after standard radical therapy (chemotherapy group). The median follow-up time was 13.4 (2.0-34.0) months. All patients survived. The 30-month EFS rates in the chemotherapy and control groups were 100% and 85.6%, respectively ( P=0.064). There were no events in the chemotherapy group, while there were 12 cases of events in the control group, including 6 cases of biochemical recurrence and 6 cases of imaging progression. The 30-month MFS rates in two groups were 100% and 91.9%, respectively ( P=0.205). After the 1 vs. 2 propensity score matching, the EFS and MFS rates in two groups were 100% vs. 85.7% ( P=0.056), and 100% vs. 92.2% ( P=0.209), respectively. The incidence rates of grade 2 and above urinary toxicity in the chemotherapy and control groups were 2.6% and 7.2% ( P=0.354), respectively. The incidence rates of grade 2 and above rectal toxicity were 5.3% and 5.1% ( P=0.711), respectively. Grade 3 and above chemotherapy-related toxicity in the chemotherapy group were leukopenia (31.6%), thrombocytopenia (2.6%) and alopecia (13.2%). Conclusion:The addition of adjuvant chemotherapy after standard radical therapy tends to improve the overall EFS of patients with highly malignant prostate cancer, and the adverse effects are tolerable, which should be confirmed by long-term follow-up results.

Objective To screen the epithelial mesenchymal transformation(EMT)-related genes in lung adenocarcinoma,perform functional enrichment analysis and construct protein interaction network(PPI).Ac-cording to the competitive endogenous RNA(ceRNA)hypothesis and the effect of gene expression on the prognosis of patients,the ceRNA network was constructed.Methods The differentially expressed genes be-tween lung adenocarcinoma tissues and normal tissues were screened by gene expression map and tumor ge-nome map database,and the genes were imported into GenClip3 to obtain EMT-related genes.Metascape was used to perform gene ontology and Kyoto encyclopedia of gene and genome enrichment analysis,and STRING database was used to construct PPI and obtain EMT key genes.The relationship between key genes and prog-nosis was analyzed by Kaplan-Meier analysis.Analysis tools such as miRTarbase,miRNet database,and EN-CORI were used to construct ceRNA networks.Results In this study,156 lung adenocarcinoma EMT-related genes and their key genes cadherin 1,interleukin-6,matrix metalloproteinase-9,platelet endothelial cell adhe-sion molecule,cyclin-dependent kinase inhibitor 2A,α1-Ⅰcollagen gene,secreted phosphoprotein 1,TIMP in-hibitor of matrix metalloproteinase-1,caveolin-1 and Zeste homologue enhance core 2(EZH2)-1 were identi-fied.The PPI of key genes was predicted,and the therapeutic drugs targeting these key genes including salvia miltiorrhiza,ginseng lu,ginseng leaf and ginseng flower were also predicted.The prognostic ceRNA regulatory network of EZH2/hsa-miR-101-3p/GSEC was constructed.Conclusion This study describes using bioinfor-matics methods system in the process of EMT gene interactions,according to the lung adenocarcinoma pa-tients clinical data to construct the prognosis of the EMT process related ceRNA network,for the treatment and prognosis of lung adenocarcinoma judgment provides a new way of thinking.