Faculty Bibliography

Purpose: This research aimed to perform an overview on adjuvant vaginal brachytherapy (VBT) in stage I to II endometrial carcinoma (EC) according to ESMO-ESGO-ESTRO risk group consensus in China from multi-institutional analysis.Materials and Methods: We retrospectively analyze patients with stage I to II EC at 13 institutions in China treated between 2003 and 2015. All patients underwent adjuvant radiotherapy and were divided into low-risk (LR), intermediate-risk (IR), high-intermediate risk (HIR) and high-risk (HR) groups according to ESMO-ESGO-ESTRO risk group consensus. XXResult(s): A total of 1048 cases were included. Stage I disease accounted for 85.9% of the cohort. Proportion of HR disease was 27.6%, HIR 17.7%, IR 27.7% and LR 27.1%. Patients received adjuvant VBT alone (n = 474), pelvic external beam radiotherapy (EBRT) alone (n = 116) or combined EBRT with VBT (n = 458). An increasing trend was found toward referrals for VBT alone. Historical data demonstrate that the clinical practice of adjuvant VBT alone increased significantly in the LR to HIR groups over the past 13 years. However, in the HR group, the proportion of VBT alone or as a boost after EBRT stayed stable in the corresponding period.All institutions commonly use High-dose-rate VBT prescribed to 0.5-cm depth from the vaginal surface with 14 and 17 different dose-fractionation schedules for VBT alone and VBT boost, respectively. The most common fractionation for VBT alone is 5 Gy in six fraction (407/474) and the most common fractionation for VBT as a boost after EBRT is 5 Gy in two fractions (178/458). Proximal 2-3 cm vagina was the most often irradiated vaginal target (61.3%). The most commonly used applicators were the multichannel vaginal cylinder (79.6%). The median follow-up time was 56 months. For LR to HIR patients, VBT alone achieved comparable survival to EBRT. Compared to EBRT, patients receiving VBT had significantly decreased incidence of grade 1-2 early and late gastrointestinal and urinary reactions, and the rate of grade 3-4 acute hematological toxicity. XXConclusion(s): There is remarkable heterogeneity among VBT dose-fractionation schedules. An increasing trend was found toward referrals for VBT alone. The clinical practice of adjuvant VBT alone increased significantly in LR to HIR groups over the past 13 years. In LR to HIR group, VBT alone achieved comparable survival to EBRT.XXCopyright

Objective: To examine genetic variants of familial hematuria (FH) associated genes in 3 families with hematuria with probands initially diagnosed with IgA nephropathy (IgAN). Methods: A retrospective analysis was performed on the clinical data, laboratory tests and genetic test results of three children with hematuria and the probands in three families with hematuria. The families were ascertained at the Department of Pediatrics, Fuzhou General Hospital of Nanjing Military Command from August 2014 to May 2018. Results: The proband of Family One, an 8-year-old boy, manifested gross hematuria. His renal biopsy pathology revealed IgAN. His father also manifested hematuria. Genetic testing showed that the proband and his father carried a heterozygous variant of the CFHR5 gene,533A>G (Asn178Ser). The child of Family Two, a 4-year-old girl, manifested hematuria. Her father, the proband of the family, was 36 years old, and manifested hematuria, proteinuria, high-frequency sensorineural deafness and renal insufficiency. He was diagnosed as IgAN according to clinical manifestations, renal pathology and routine immunohistochemistry without renal biopsy electron microscopy, renal tissue type Ⅳ collagen α3, α4, α5 chains immunofluorescence and skin type Ⅳ collagen α5 chain immunofluorescence. Genetic testing showed that the girl carried a heterozygous variant of the COL4A5 gene,566G>T (Gly189Val), and her father carried the hemizygous variant. The child of Family Three, a 7-year-old girl, manifested hematuria and proteinuria. Her mother, the proband of the family, was 34 years old, and manifested hematuria and proteinuria as well. The proband was diagnosed as IgAN by the same method used for Family Two. The girl's grandfather died of uremia at the age of 44. Genetic testing showed that the girl and her mother carried a heterozygous variant 539G>A (Gly180Glu)in COL4A5 gene. Conclusions: The variant of the CFHR5 gene identified in Family One is of uncertain signifance, and the two variants of the COL4A5 gene identified in Families Two and Three are pathogenic. The probands of Families Two and Three are diagnosed as Alport syndrome. The study suggests that clinicians should examine genetic variants of FH associated genes in families with hematuria when the probands were diagnosed as IgAN by their clinical manifestations, renal pathology and routine immunohistochemistry.

A brain-enriched protein tyrosine phosphatase termed STEP46 (striatal enriched phosphatase) was previously isolated and characterized. Immunological studies with a STEP monoclonal antibody recognized several STEP-immunoreactive proteins, and suggested that additional STEP-related polypeptides existed. This study reports the isolation of two alternatively spliced transcripts of the STEP gene. One of these, STEP20 (with a predicted molecular mass of 20 kDa) was further characterized and found to lack the conserved tyrosine phosphatase domain. Northern analysis detected a 2.8 kb STEP20 message in mouse brain. The second alternatively spliced transcript, STEP61, has a 5'-extended open reading frame that encodes a protein with a predicted molecular mass of 61 kDa and contains a single tyrosine phosphatase domain. The exon-intron organization responsible for the novel STEP20 and STEP61 sequences was determined in the mouse STEP genomic DNA. We propose that the original STEP46, along with STEP20 and STEP61, are members of a brain-enriched subfamily of protein tyrosine phosphatases, and that STEP isoforms may have distinct functions within the central nervous system.