Fingolimod protects against experimental necrotizing enterocolitis by regulating intestinal T cell differentiation.

Background: Necrotizing enterocolitis (NEC)-the leading cause of neonatal death-has been shown to be associated with an excessive inflammatory response of the intestines. Fingolimod has shown efficacy in treating many inflammatory diseases. In this study, we aimed to explore the protective effects of fingolimod on a mouse model of NEC. Methods: Experimental NEC was induced in 5-day-old C57BL/6 neonatal mice. Many methods include Hematoxylin and eosin (H&E), immunofluorescence staining, polymerase chain reaction (PCR) and western blot were used to evaluate the degreed of inflammation of NEC. A model of T-cell co-culture system in vitro was used to explain the way Fingolimod acted on T cell. We also detected the NEC associated brain injury by immunofluorescence staining. Results: Fingolimod treatment ameliorated NEC-induced intestinal injury, reduced inflammatory T cell infiltration, and regulated the balance between T helper 17 (Th17) and regulatory T cells in intestinal tissues. In addition, fingolimod treatment was found to blunt the pro-inflammatory phenotype of activated macrophages and decrease interleukin-17 (IL-17) secretion. Fingolimod treatment also ameliorated NEC-induced neuroinflammation. Conclusions: Fingolimod can protect neonatal mice from NEC-related death by ameliorating intestinal injury and attenuating excessive inflammatory responses. These effects may be mediated through an improved Th17/Treg balance, which may result from direct and indirect effects of fingolimod on T cell infiltration and macrophage differentiation.

Perianorectal abscesses and fistula due to ingested jujube pit in infant: Two case reports.

BACKGROUND: About 90% of perianal infection is caused by cryptoglandular infection. Only a few cases of peritonitis or intra-abdominal abscesses secondary to perforation of the digestive tract by an ingested foreign body have been reported. The most common sites of impaction and perforation include the appendix, cecum and the terminal ileum. The rectum is an unusual site of foreign body impaction. This report intends to highlight that ingested foreign body impacted in the rectum is an extremely rare cause of perianal abscess and subsequent fistula in infants. CASE SUMMARY: Two cases of perianal abscess and fistula due to ingested jujube pit impacted in the rectum are reported. Both cases are infants with free previous medical history suffered from recurrent perianal infection. The caregivers of the two patients denied ingestion of a foreign body or any history of trauma. Physical examination combined with ultrasound or computed tomography scan established the diagnosis. Both of the patients underwent operation under general anesthesia. In case 1, a jujube pit with sharp ends was discovered embedded within a subcutaneous fistula. The jujube pit was then removed intact along with fistula resection. The wound was successfully laid open to allow healing by secondary intention. In case 2, a jujube pit was found with its sharp end puncturing the rectum, surrounded by pus and necrotic tissue. Subsequent incision and adequate drainage were performed. The whole jujube pit was then removed from the abscess cavity at the same time. Both patients received colonoscopy to rule out inflammatory bowel disease or other potential damages by the ingested jujube pit. The postoperative period was uneventful. At 1.5 year follow-up, no recurrent abscess or fistula were found in either patient. CONCLUSION: An impacted foreign body must not be overlooked as an unusual cause of perianal abscess and fistula, especially in young children.

Exome sequencing identifies predisposing and fusion gene in ganglioneuroma, ganglioneuroblastoma and neuroblastoma.

This study intended to gain new insight into the genetic basis underlying ganglioneuroma (GN), ganglioneuroblastoma (GNB), and neuroblastoma (NB). Three fresh-frozen surgically resected tumor tissues (GN1, GNB1, and NB1) and matched blood samples (GN2, GNB2, and NB2) were respectively obtained from three pediatric patients with GN, GNB, and NB. After exome sequencing, we predicted the somatic single nucleotide variants (SNV) and insertion and deletion (InDel), and screened the predisposing genes. Finally, we detected and filtered the fusion gene using Fusionmap. Exome sequencing identified 815, 985, and 884 somatic SNV, and 56, 43, and 34 InDel for GN, NB, and GNB respectively. Total 29, 19 and 37 predisposing genes were identified from GN, GNB and NB samples, such as PIK3CA (GN), MUC4 (GN), PML (NB), TFR2 (GNB), and MAX (GNB). Additionally, four common fusion genes, such as HOXD11-AGAP3 and SAMD1-CDC42EP5, were identified from three tumor samples. Moreover, SAMD1-CDC42EP5 was also a common fusion position in three blood samples. These previously unrecognized predisposing genes, such as PIK3CA, MUC4, PML, TFR2 and MAX, and fusion genes, like HOXD11-AGAP3, and SAMD1-CDC42EP5 may have the potential to impact the progression and development of neuroblastic tumors.

A single center clinical analysis of children with neuroblastoma.

In the present study, the cases of 59 children diagnosed with neuroblastoma (NB) were retrospectively analyzed to assess the association between the short-term efficacy of treatment and prognostic factors. In total, 59 patients with NB that were diagnosed between July 1, 2008 and June 30, 2013 at Shanghai Children's Hospital were enrolled in the present study. The follow-up was performed until December 31, 2013, and the data revealed that 43 patients (72.9%) achieved complete remission (CR) or partial remission (PR). The 3-year overall survival (OS) rate of patients with stage I, II, III, IV and IVs disease was 100, 100, 65.6, 34.8 and 85.7%, respectively (P=0.02). The 3-year OS and event-free survival rates were evidently increased in patients with favorable histology compared with the rates in the patients with unfavorable histology (P=0.046 and 0.030, respectively). Univariate statistical analysis revealed that the factors significantly associated with prognosis were patient age, tumor stage and risk group (P=0.004, 0.02 and 0.001, respectively). The present study identified that tumor stage, risk group and patient age are important prognostic factors for NB. An age of 18 months was also hypothesized to be the cut-off for the prognosis of patients.