Although therapies against neuroblastoma (NBM) have advanced, the patients still suffer from poor prognoses due to distal metastasis or the occurrence of multidrug resistance. Accumulating evidence has proved that chemicals derived from natural products possess potent anti-NBM properties or can be used as adjuvants for chemotherapy. In the present study, we demonstrated that 6 ′ -O-galloylpaeoniflorin (GPF), a galloylated derivative of paeoniflorin isolated from the roots of Paeonia lactiflora Pall, exerted significant inhibitory effects on proliferation and invasion of SH-SY5Y cells (an NBM cell line) and enhanced the sensitivity of SH-SY5Y cells to cisplatin in vitro. Further studies showed that GPF treatment upregulated miR-489 in NBM cells via activating AMP-activated protein kinase (AMPK). We also demonstrated that similar to GPF treatment, miR-489 exhibited a significant anti-NBM capacity. Further studies showed that miR-489 directly targeted the X-linked inhibitor of apoptosis protein (XIAP). Overall, our results indicated that GPF possessed an evident anti-NBM capacity dependent on AMPK/miR-489/XIAP pathway, providing an emerging strategy for clinical treatment of NBM.

Background: The incidence of Hirschsprung disease (HSCR) is nearly 1/5000 and patients with HSCR are usually treated through surgical intervention. Hirschsprung disease-associated enterocolitis (HAEC) is a complication of HSCR with the highest morbidity and mortality in patients. The evidence on the risk factors for HAEC remains inconclusive to date. Methods: Four English databases and four Chinese databases were searched for relevant studies published until May 2022. The search retrieved 53 relevant studies. The retrieved studies were scored on the Newcastle–Ottawa Scale by three researchers. Revman 5.4 software was employed for data synthesis and analysis. Stata 16 software was employed for sensitivity analysis and bias analysis. Results: A total of 53 articles were retrieved from the database search, which included 10 012 cases of HSCR and 2310 cases of HAEC. The systematic analysis revealed anastomotic stenosis or fistula [I 2=66%, risk ratio (RR)=1.90, 95% CI 1.34–2.68, P<0.001], preoperative enterocolitis (I 2=55%, RR=2.07, 95% CI 1.71–2.51, P<0.001), preoperative malnutrition (I 2=0%, RR=1.96, 95% CI 1.52–2.53, P<0.001), preoperative respiratory infection or pneumonia (I 2=0%, RR=2.37, 95% CI 1.91–2.93, P<0.001), postoperative ileus (I 2=17%, RR=2.41, 95% CI 2.02–2.87, P<0.001), length of ganglionless segment greater than 30 cm (I 2=0%, RR=3.64, 95% CI 2.43–5.48, P<0.001), preoperative hypoproteinemia (I 2=0%, RR=1.91, 95% CI 1.44–2.54, P<0.001), and Down syndrome (I 2=29%, RR=1.65, 95% CI 1.32–2.07, P<0.001) as the risk factors for postoperative HAEC. Short-segment HSCR (I 2=46%, RR=0.62, 95% CI 0.54–0.71, P<0.001) and transanal operation (I 2=78%, RR=0.56, 95% CI 0.33–0.96, P=0.03) were revealed as the protective factors against postoperative HAEC. Preoperative malnutrition (I 2=35 % , RR=5.33, 95% CI 2.68–10.60, P<0.001), preoperative hypoproteinemia (I 2=20%, RR=4.17, 95% CI 1.91–9.12, P<0.001), preoperative enterocolitis (I 2=45%, RR=3.51, 95% CI 2.54–4.84, P<0.001), and preoperative respiratory infection or pneumonia (I 2=0%, RR=7.20, 95% CI 4.00–12.94, P<0.001) were revealed as the risk factors for recurrent HAEC, while short-segment HSCR (I 2=0%, RR=0.40, 95% CI 0.21–0.76, P=0.005) was revealed as a protective factor against recurrent HAEC. Conclusion: The present review delineated the multiple risk factors for HAEC, which could assist in preventing the development of HAEC.