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Complications, such as fecal soiling, incontinence, and constipation, are major health issues for patients with anorectal malformations (ARMs) after surgery. Dysplasia of the caudal spinal cord is an increasingly pivotal area in the field of postoperative complications for patients with ARMs. However, the existing research has not fully defined the mechanism underlying ARMs development. The neurogenic locus notch homolog (Notch) signaling pathway comprises several highly conserved proteins that are involved in spinal cord developmental processes. In the present study, the emerging role of Notch1 in fetal lumbosacral spinal cords was investigated in a rat model of ARMs using ethylene thiourea. Immunohistochemical staining, western blot and quantitative reverse transcription real-time polymerase chain reaction were utilized to analyze spatiotemporal expression of Notch1 on embryonic days (E) 16, E17, E19, and E21. The expression levels of the neuronal marker neurofilament and recombination signal-binding protein-J protein were evaluated for temporal correlations to Notch1 expression. The results implied that Notch1 expression was reduced in lumbosacral spinal cord neurons of ARMs embryos compared to control embryos. These results showed that, in ARMs embryos decreased Notch1 expression is related to the dysplasia of the caudal spinal cord during embryogenesis, indicating that Notch signaling may participate pathogenic embryonic lumbosacral spinal development and may be associated with postoperative complications of ARMs.

Hypoxia-inducible factor-1-alpha (HIF-1α) activates the transcription of many genes that code for proteins involved in angiogenesis, glucose metabolism, cell proliferation/survival, and invasion/metastasis. However, the mechanisms between HIF-1 and its downstream target genes are still poorly understood. Our experimental results had shown that nuclear HIF-1α proteins were significantly induced after HepG2 cells treatment with 1% O 2 for 6 h and reached the peak expression level in 24 h. Meanwhile, the results of RT-qPCR and Western-blotting showed that HIF-1α and cathepsin B (CTSB) expressions increased with a similar pattern in response to hypoxia in the HepG2 cells. Additionally, based on bioinformatics analysis, we identified a hypoxia response element in the CTSB promoter, indicating a possible association between HIF-1α and CTSB. Moreover, luciferase assay was performed to reflect the transcriptional activity mediated through the HIF-1α binding HRE within the CTSB promoter. Furthermore, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (CHIP) revealed a specific HIF-1α binding activity to the CTSB gene promoter. For the first time, we demonstrated that CTSB is a new HIF-1α-target gene. We believe these findings will contribute to the research and development of neoplasm-targeted therapies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to design an individualized biofeedback program based on the underlying dysfunctions and to assess the short-term and long-term clinical and quality-of-life outcomes for patients with imperforate anus., Methods: Thirty-one patients were treated using an individualized biofeedback program according to their different dysfunctions after having completed the assessment of the anorectal function. Many special biofeedback training methods that consist of strengthening the perianal muscles biofeedback, sensory discrimination biofeedback, synchronizing external sphincter contraction biofeedback, and improving defecation dynamic biofeedback were selected to make up the individualized biofeedback training program. The clinical scores and quality-of-life scores were assessed in the short-term and long-term follow-up., Results: The clinical scores and quality-of-life scores of patients before training, after biofeedback training, at short-term follow-up, and at long-term follow-up were 3.2 +/- 1.1 and 8.7 +/- 1.1, 5.2 +/- 0.6 and 11.0 +/- 0.8, 5.1 +/- 0.6 and 10.8 +/- 0.9, and 4.6 +/- 0.7 and 10.1 +/- 0.7, respectively. After biofeedback training, the strength of the perianal muscles were increased significantly, the abnormal rectal threshold sensation and defecation dynamic reverted to normal in all patients, and 82% patients who have no external anal sphincter reflex acquired the new reflex. In the short-term follow-up, 12 (57%) patients maintained the clinical outcome, and only 9 (43%) patients have regressions slightly. At long-term follow-up, 7 (33%) patients maintained the clinical outcome very well, and 14 (67%) patients had regressed. Although the clinical and quality-of-life scores have decreased slightly at follow-up, they were still significantly increased compared with those before biofeedback training., Conclusions: The individualized biofeedback is more suitable for improvement of the clinical outcome and the quality of life, and maintained a good clinical outcome and quality of life on the short-term and long-term follow-ups.