Bowel function and features of bowel dysfunction in preschool children with anorectal malformation type rectoperineal and rectovestibular fistula.

Anorectal malformations (ARMs) of the rectoperineal and rectovestibular fistula type (RPF/RVF) generally have a good prognosis but may be accompanied by bowel dysfunction, especially constipation. Bowel dysfunction in preschoolers may persist into adolescence and adulthood, exerting a negative effect on their quality of life. This study was designed to evaluate bowel function and identify the features of bowel dysfunction in preschoolers with RPF/RVF across type and sex differences. A total of 159 preschoolers with RPF/RVF (male RPF group, n = 95; female RPF group, n = 26; RVF, n = 38) and 128 normal control preschoolers (control group, n = 128; female control group, n = 35), according to the bowel function score (BFS) obtained through a questionnaire survey, the BFS items in the questionnaire, and the clinical characteristics of patients were compared among groups. The rates of bowel dysfunction (BFS < 17) were 27.2% and 50.0% in the RPF and RVF groups, respectively. Normal rates of BFS items, namely, ability to hold back defecation, feels/reports of the urge to defecate, frequency of defecation, and constipation, in the RPF and RVF groups were significantly lower than those in the control and female control groups (all p < 0.05). After subgroup analysis among the male RPF, female RPF, and RVF groups, higher rates of normal bowel function and ability to hold back defecation were found in the male RPF group than in the female RPF and RVF groups (p < 0.05). Normal rates of feels/reports of the urge to defecate were higher in the male and female RPF groups than in the RVF group (all p < 0.05). The rate of never soiling in the male RPF group was significantly higher than that in the RVF group (p < 0.05).  Conclusions: In patients with RPF/RVF, bowel dysfunction is still prevalent, characterized by inadequate ability to hold back defecation, inability to feel/report the urge to defecate, soil, less frequent defecation, and constipation. However, male RPF patients had better overall bowel function than female RPF or RVF patients, including more adequate ability to hold back defecation and feels/reports of the urge to defecate and slighter soiling, which may be linked to early age at surgery, low occurrences of low sacral ratio, and tethered cord in male RPF.  Trial registration: This study was retrospectively registered in ClinicalTrials.gov on 09/01/2023 (NCT05716230). What is Known: • Rectoperineal and rectovestibular fistula (RPF/RVF) of the anorectal malformation (ARM) type has a good prognosis but may cause bowel dysfunction, especially constipation. • Bowel dysfunction at preschool age may lead to social and psychological disorders that undermine the quality of life in adolescence and adulthood. What is New: • Bowel function in preschoolers with RPF/RVF was deeply evaluated in a relatively large number of patients and normal control children. • Features of bowel dysfunction in RPF/RVF preschoolers across type and gender differences were identified in this study.

A convenient nomogram for predicting early death or liver transplantation after the Kasai procedure in patients with biliary atresia.

PURPOSE: Many patients with biliary atresia (BA) after the Kasai procedure (KP) progress to death or require liver transplantation to achieve long-term survival; however, most cases of death/liver transplantation (D/LT) occur in the early period after KP (usually within 1 year). This study was designed to construct a convenient nomogram for predicting early D/LT in patients with BA after KP. METHODS: A BA cohort was established in May 2017, and up to May 2023, 112 patients with 1-5 years of follow-up were enrolled in the study and randomly (ratio, 3:1) divided into a training cohort for constructing a nomogram (n = 84) and a validation cohort (n = 28) for externally validating the discrimination and calibration. The training cohort was divided into two groups: the early D/LT group (patients who died or had undergone LT within 1 year after KP [n = 35]) and the control group (patients who survived through the native liver more than 1 year after KP [n = 49]). Multivariate logistic regression and stepwise regression were applied to detect variables with the best predictive ability for the construction of the nomogram. The discrimination and calibration of the nomogram were internally and externally validated. RESULTS: The Kaplan-Meier (K-M) curve showed an actual 1-year native liver transplantation (NLS) rate of 57.1% and an estimated 2-year NLS rate of 55.2%. By multivariate regression and stepwise regression, age at KP, jaundice clearance (JC) speed 1 month after KP, early-onset PC (initial time < 36.5 days) after KP, sex, aspartate aminotransferase-to-platelet ratio index (APRI), and weight at KP were identified as the independent variables with the best ability to predict early D/LT and were used to construct a nomogram. The developed nomogram based on these independent variables showed relatively good discrimination and calibration according to internal and external validation. CONCLUSION: Most D/LTs were early D/LTs that occurred within 1 year after KP. The established nomogram based on predictors, including sex, weight at the KP, the APRI, age at the KP, JC speed 1 month after the KP, and early PC, may be useful for predicting early D/LT and may be helpful for counseling BA patients about patient prognosis after KP. This study was retrospectively registered at ClinicalTrials.gov (NCT05909033) in June 2023.

Correlation between congenital pelvic floor muscle development assessed by magnetic resonance imaging and postoperative defecation.

OBJECTIVE: Children with congenital anorectal malformation (CAM) experience challenges with defecation. This study aims to assess defecation in preschool-age children with CAM and to evaluate the correlation between pelvic floor muscle developed assessed by magnetic resonance imaging (MRI) and postoperative defecation. METHODS: We collected clinical data and MRI results from 89 male children with CAM. The bowel function scores for children with Perineal (cutaneous) fistula, Rectourethral fistula(Prostatic or Bulbar), and Rectovesical fistula were computed. MRI scans were subjected to image analysis of the striated muscle complex (SMC). The association between pelvic floor muscle score and bowel function score was examined using the Cochran-Armitage Trend Test. RESULTS: We observed that 77.4% of the SMC scores by MRI for Perineal fistula were good. The Rectourethral fistula SMC score was 40.6% for moderate and 59.4% for poor. The SMC score for Rectovesical fistula was 100% for moderate. Furthermore, 77.4% of patients with Perineal fistula had bowel function scores (BFS) ≥ 17 points. Among those with Rectourethral fistula and Rectovesical fistula, 12.5% and 0 had BFS ≥ 17 points, respectively. An analysis of muscle development and bowel function in patients with Rectovesical fistula, Rectourethral fistula, and Perineal fistula revealed a correlation between SMC development and BFS. Subgroup analysis showed that the Perineal fistula had statistical significance; however, the Rectourethral fistula and Rectovesical fistula were not statistically significant. CONCLUSION: A correlation exists between pelvic floor muscle development and postoperative defecation in children with Perineal fistula.

Bowel function at preschool and early childhood age in children with long-segment Hirschsprung disease.

Bowel dysfunction has been proven to be the most typical complication of long-segment Hirschsprung disease (LSHD). Additionally, bowel dysfunction in preschool and early childhood should be properly assessed, because it may result in persistent bowel dysfunction, social issues, and depression in adolescence and adulthood. This study evaluated bowel function during preschool and early childhood in patients with LSHD. A cross-sectional bowel function score (BFS) questionnaire survey was conducted on 270 infants with short-segment Hirschsprung disease (SSHD) and LSHD who underwent pull-through (PT) between January 2014 and December 2019 at the Children's Hospital of Nanjing Medical University. One hundred ninety patients who consented to the survey were asked to complete the questionnaire and were divided into two groups: the LSHD group (n = 42) and the SSHD group (n = 148). Bowel function outcomes were assessed by using a questionnaire. The total BFS score in the LSHD group was significantly lower than that in the SSHD group (15.0 [14.0, 17.0] vs. 18.0 [16.0, 19.0], p < 0.05) and did not improve with age (p > 0.05). Independent BFS items with lower scores were discovered in LSHD than in SSHD, including the capacity to hold back defecation, feeling/reporting the urge to defecate, frequency, soiling, and accidents (all p < 0.05). After subgroup analysis of follow-up age (3-5 years, 5 ~ 7 years, and > 7 years), there was no difference between the score of ability to hold back defecation over 7 years old and feeling/reporting the urge to defecate over 5 years old (all p > 0.05). The frequency and soiling scores were lower in the LSHD group than in the SSHD group over 5 years of age (all p < 0.05). Fortunately, there was no difference in constipation scores and social problems between the LSHD and SSHD groups in every sub-follow-up group (all p > 0.05).  Conclusion: Overall, bowel function at preschool and early childhood age was poorer in LSHD than in SSHD and did not improve with age. However, the ability to hold back defecation and feeling/reporting the urge to defecate with age in LSHD may be similar to those in SSHD. Simultaneously, the frequency, soiling, and number of accidents were consistently worse in the LSHD group.  Trial registration: This study was retrospectively registered in the ClinicalTrials database.gov (NCT05461924) in August 2022. What is Known: • Bowel function in SSHD is satisfactory or near-normal, and the general consensus is that the longer the aganglionic segment, the worse the bowel function after surgery. • Bowel functional outcomes of LSHD were not defined, and the limited reports of bowel functional outcomes compared with SSHD were extensively varied. Bowel dysfunction at preschool and early childhood may lead to persistent bowel dysfunction, social problems, and depression in adolescence or adulthood. What is New: • Bowel function in preschool and early childhood in patients with LSHD has not been defined and should be thoroughly assessed in a larger group of patients with precise definitions of incontinence or soiling. • The present study was primarily designed to evaluate bowel function at preschool and early childhood age in LSHD compared with SSHD in a relatively large number of HD cases using BFS.

Fecal calprotectin as a non-invasive marker for the prediction of post-necrotizing enterocolitis stricture.

PURPOSE: This study aimed to evaluate the clinical utility of fecal calprotectin (FC) levels during the necrotizing enterocolitis (NEC) episode to predict the onset of post-NEC intestinal stricture. METHODS: The medical records of patients with NEC treated from April 2020 to April 2022 were recorded for this study. FC was quantified at the acute phase of NEC. FC levels were compared in patients with or without intestinal stricture. Receiver operating characteristics (ROC) analysis was constructed to determine optimal cut-offs of FC for post-NEC intestinal stricture. RESULTS: A total of 50 infants with NEC were enrolled in this study and 14 (28%) of them eventually developed intestinal stricture. All children with intestinal stricture underwent one-stage surgery and all made it through the follow-up period alive. The median FC level was 1237.55 (741.25, 1378.80) ug/g in patients with intestinal stricture and it was significantly higher than that in the non-stricture group [158.30 (76.23, 349.13) ug/g, P < 0.001]. FC had good diagnostic accuracy for predicting intestinal stricture, according to ROC curve analysis, with an AUC area of 0.911. At an optimal cut-off value of 664.2 ug/g, sensitivity and specificity were 85.71% and 91.67%, respectively. CONCLUSION: As a non-invasive parameter, FC has excellent efficacy and accuracy in predicting post-NEC intestinal stricture. Increased FC levels at the acute phase of NEC were associated with the development of intestinal stricture.

Initial surgical treatment of necrotizing enterocolitis: a meta-analysis of peritoneal drainage versus laparotomy.

Necrotizing enterocolitis (NEC) in premature infants is associated with high morbidity and mortality, and the optimal intervention remains uncertain. To compare the mortality of primary peritoneal drainage versus primary peritoneal laparotomy as initial surgical intervention for NEC. All data were extracted from PubMed, Embase, and the Cochrane Library. Studies published up to December 2021. Patients with NEC. Studies centered on primary peritoneal drainage and primary peritoneal laparotomy as the initial surgical treatment. Mortality outcomes were available for both interventions. Randomized controlled trials, retrospective cohort studies, and case series in peer-reviewed journals. Language limited to English. Odds ratio (OR) with 95% confidence intervals (CIs) was used to evaluate mortality outcome. Subgroup analyses and linear regression were performed to ascertain the association between mortality pre-specified factors. Data of 1062 patients received peritoneal drainage and 2185 patients received peritoneal laparotomy from five case series, five retrospective cohort studies, and three randomized controlled trials. Peritoneal drainage caused similar mortality (OR 1.49, 95% CI 0.99-2.26) compared with peritoneal laparotomy as initial surgical management for NEC infants. The subgroup analysis of study design, sample size, birth weight, and sex showed similar findings, but inconsistent results were found for country (USA: 1.47, 95% CI 0.90-2.41; Canada: 2.53, 95% CI 0.30-21.48; Australia: 10.29, 95% CI 1.03-102.75; Turkey: 0.09, 95% CI 0.01-0.63) and gestational age (age mean difference < 3: 1.23, 95% CI 0.72-2.11; age mean difference ≥ 3: 2.29, 95% CI 1.04-5.05). No statistically significance was found for the linear regression between mortality and sample size (P = 0.842), gestational age (P = 0.287), birth weight (P = 0.257), sex (P = 0.6). Small sample size, high heterogeneity, NEC, and spontaneous intestinal perforation (SIP) had to be analyzed together, lack of selection criteria for the future selection of an intervention, and no clear, standardized procedures.   Conclusion: There was no significant difference in mortality between peritoneal drainage and laparotomy as initial surgical intervention. The results suggest that either intervention could be used in selected patients. What is Known: • Necrotizing enterocolitis (NEC) in premature infants is associated with high morbidity and mortality, and the optimal intervention remains uncertain. What is New: • No significant difference of mortality between peritoneal drainage and laparotomy as initial surgical intervention.

Risk factors for the occurrence and recurrence of acute cerebellar ataxia: a retrospective observational study.

OBJECTIVE: There is little evidence to support a correlation between abdominal surgery and acute cerebellar ataxia (ACA). We reviewed the records of children with ACA treated at our institution to analyze risk factors for ACA. METHODS: Clinical data of 442 children with ACA treated at Children's Hospital of Nanjing Medical University between November 2015 and June 2019 were retrospectively analyzed. Univariate and multivariate analyses were performed to determine risk factors for the occurrence and recurrence of ACA. RESULTS: In total, 442 children with ACA were included in this study. Multivariate logistic regression analysis showed age (p = 0.009), infection (p < 0.001), vaccination (p < 0.001), head trauma (p < 0.001), intussusception surgery (IS) (p < 0.001), operation for indirect inguinal hernia (p < 0.001), and operation for congenital gastrointestinal malformation (p < 0.001) were independent risk factors for ACA occurrence. Univariate analysis showed that only IS (p < 0.001) was associated with ACA recurrence. CONCLUSIONS: Surgeons should be aware that age, infection, vaccination, head trauma, and history of abdominal surgery are associated with ACA, while IS is a risk factor for ACA recurrence.

The difference of gut microbiome in different biliary diseases in infant before operation and the changes after operation.

BACKGROUND: Evidence supports an association between cholestatic liver disease and changes in microbiome composition. Nevertheless, the identification of this special type of biliary atresia from non-biliary atresia cholestasis is still a major clinical difficulty. The purpose of this study is to compare the differences in the composition of gut microbiome between infants with biliary atresia and infant with non-biliary atrestic cholestasis, to find new ways to identify and diagnose these two diseases early, to understand the influence of the presence or absence of bile on the composition of the gut microbiome in infants with cholestasis. METHODS: Using 16S rDNA gene sequencing technology to analyze the intestinal flora of the participants. RESULTS: In terms of diversity, there is an obvious structural separation in the intestinal microbiota of the BA group and the CD group, and this structural separation also exists in the comparison between the two groups before surgery. Taxonomic analysis demonstrated that the two groups showed an increase in Proteobacteria and Firmicutes before surgery, and the relative abundance of potential pathogens such as Shigella, Streptococcus, Klebsiella, etc. increased, potential probiotics such as Bifidobacteria and Lactobacillus decreased, but the relative abundance of each genus was different between groups. It was found that Enterococcus, Ralstonia, Nitriliruptoraceae, etc. were differentially enriched in the BA group, the CD group are mainly enriched in Veillonella, Clostridium_sensu_stricto_1 and Lactobacillus. Functional analysis of the groups showed that the BA group mainly focused on the processes of energy release processes, and the CD group mainly focused on the biosynthesis of amino-acids to consume energy. CONCLUSIONS: The composition of intestinal flora is different between biliary atresia and non-biliary atretic cholestasis. Enterococcus, Ralstonia, etc. may become biomarkers for the identification and diagnosis of both.

Baseline assessment of enhanced recovery after pediatric surgery in mainland China.

BACKGROUND: Enhanced recovery after surgery (ERAS) is a clinical pathway that optimizes perioperative management based on evidence-based medicine. ERAS has been gradually introduced to pediatric surgery in recent years. However, there are limited reports on its overall implementation. We aimed to determine the implementation of ERAS in patients who received pediatric surgery in mainland China. METHODS: We designed a questionnaire involving 17 key ERAS elements and sent the questionnaire to 66 chiefs of pediatric surgery distributed throughout 31 provinces in mainland China to obtain a baseline assessment of the assimilation of ERAS protocols in the care of congenital biliary dilatation (CBD). RESULTS: A total of 66 questionnaires were collected. The range of elements implemented at participating centers was 4-16, with a mean of 10.23. The least commonly practiced elements were administration of non-opioid preoperative analgesia (6 centers, 9.09%), prevention of postoperative nausea and vomiting [PONV] (9 centers, 13.64%), and postoperative pain management (26 centers, 39.39%). CONCLUSIONS: The implementation of elements differed from center to center. Measures relying primarily on anesthesiologists had lower execution. The adherence to ERAS elements was often inhibited by a lack of institutional support, poor knowledge of ERAS protocols, and difficulties in coordinating multidisciplinary care, as well intransigence in changing surgical practices out of fear of liability for poor outcomes.

Intrauterine exposure to oxidative stress induces caspase-1-dependent enteric nerve cell pyroptosis.

PURPOSE: This study determined whether oxidative stress causes the developmental abnormalities of the enteric nervous system during the embryonic period. METHODS: Using the test results of tissue specimens of children with Hirschsprung disease (HSCR), we established a pregnant rat model of oxidative stress and a cellular oxidative stress model to conduct related molecular, cellular, and histopathological experiments for exploration and validation. RESULTS: The results of the quantitative real-time polymerase chain reaction assay indicated overexpression of pyroptosis markers (NLRP3, ASC, and caspase-1) in HSCR lesions and newborn pups in the oxidative stress group (treated with D-galactose). The expression of cathepsin D was significantly decreased in intestinal tissues of newborn pups in the oxidative stress group compared to the control group. Reactive oxygen species scavengers (N-acetyl-cysteine, NAC), the caspase-1 inhibitor (VX-765), and the NLRP3 siRNA could reverse the release of LDH, decrease the number of propidium iodide stained cells, and reduce the percentage of TUNEL/caspase-3 double-positive cells in the H2O2-treated group. CONCLUSION: Oxidative stress can induce the death of enteric nerve cells by activating caspase-1-dependent pyroptosis through NLRP3 inflammasomes, which may contribute to abnormal enteric nervous system development.

Peptide Derived from AHNAK Inhibits Cell Migration and Proliferation in Hirschsprung's Disease by Targeting the ERK1/2 Pathway.

Hirschsprung's disease (HSCR) is characterized by the lack of ganglion cells in the distal part of the digestive tract. It occurs due to migration disorders of enteric neural crest cells (ENCCs) from 5 to 12 weeks of embryonic development. More and more studies show that HSCR is a result of the interaction of multiple genes and the microenvironments, but its specific pathogenesis has not been fully elucidated. Studies have confirmed that many substances in the intestinal microenvironment, such as laminin and ß1-integrin, play a vital regulatory role in cell growth and disease progression. In addition to these high-molecular-weight proteins, research on endogenous polypeptides derived from these proteins has been increasing in recent years. However, it is unclear whether these endogenous peptides have effects on the migration of ENCCs and thus participate in the occurrence of HSCR. Previously, our research group found that compared with the normal intestinal tissue, the expression of AHNAK protein in the stenosed intestinal tissue of HSCR patients was significantly upregulated, and overexpression of AHNAK could inhibit cell migration and proliferation. In this study, endogenous peptides were extracted from the normal control intestinal tissue and the stenosed HSCR intestinal tissue. The endogenous polypeptide expression profile was analyzed by liquid chromatography-mass spectrometry, and multiple peptides derived from AHNAK protein were found. We selected one of them, "EGPEVDVNLPK", for research. Because there is no uniform naming system, this peptide is temporarily named PDAHNAK (peptide derived from AHNAK). This project aims to clarify the potential role of PDAHNAK in the development of HSCR and to further understand its relationship with its precursor protein AHNAK and how they contribute to the development of HSCR.

Gastrointestinal failure score in children with traumatic brain injury.

BACKGROUND: To review the value of the gastrointestinal failure (GIF) score in children with different degrees of traumatic brain injury (TBI) by analyzing the correlation between outcome and gastrointestinal function. METHODS: A total of 165 children with TBI who were diagnosed and treated in the surgical intensive care unit (SICU) for longer than 72 h between August 2017 and September 2019 were analyzed. Admission parameters included sex, age, Glasgow Coma Scale (GCS) score, body mass index (BMI), leukocyte count, C-reactive protein (CRP), hemoglobin (Hb), hematocrit (Hct), blood glucose, lactic acid, procalcitonin (PCT), albumin, plasma osmotic pressure, prothrombin time (PT) and activated partial thromboplastin time (APTT). To predict outcomes, the Pediatric Sequential Organ Failure Assessment (SOFA) score, Pediatric Clinical Illness Score (PCIS), and mean GIF score for the first three days were combined. RESULTS: The percentage of patients with gastrointestinal dysfunction on the first day was 78.8 %. Food intolerance (FI) and intra-abdominal hypertension (IAH) developed in 36.4 and 21.8 % of the patients, respectively. The GIF score and mean GIF score for the first three days were significantly different between children with different degrees of TBI (P < 0.05); these scores were also significantly different between patients who died and those who survived (P < 0.05). The mean GIF score for the first three days was identified as an independent risk factor for mortality (odds ratio > 1, 95 % confidence interval = 1.457 to 16.016, P < 0.01), as was the PCIS. Receiver operating characteristic (ROC) curve analysis suggested that the mean GIF score for the first three days had the same calibrating power as the PCIS in discriminating the risk of death of children. CONCLUSIONS: The incidence of gastrointestinal dysfunction in children with TBI is high. The GIF score has the ability to reflect the status of the gastrointestinal system. The mean GIF score for the first three days has high prognostic value for ICU mortality in the SICU.

Biliary atresia in twins'population: a retrospective multicenter study in mainland China.

AIM: We evaluated the demographic of biliary atresia (BA) children from twins family and aimed to investigated what it can add to the twins' literature and our understanding of the disease. METHODS: This study contains 11 medical centers in mainland China and the medical record of twins with BA was retrospectively analyzed from January 2012 to December 2018. Follow-up was carried out by out-patient review and questionnaire. RESULTS: The study included 19 twin pairs in whom there was discordance for BA. Sixteen (84.2%) affected twin underwent Kasai Procedure (KP); median age at KP was 78 (49-168) days. There were ten affected twins that became jaundice-free at 3 months post-KP, and eight occurred with different degrees of cholangitis post-KP. Six affected twins received Liver Transplantation (LT) successfully. The 2 year native liver survival rate and the 2 year overall survival rate of affected twins were 61.1 and 94.4%, respectively. There were three affected monozygotic (MZ) twins and one healthy co-twin with BA-associated congenital malformations, all of which were cardiac malformations. The number of virus infection of affected MZ twins was significantly more (p = 0.04) than affected dizygotic (DZ) twin. CONCLUSIONS: Discordance for BA in 19 pairs of twins supported that BA may be related to genetic phenotype or penetrance. The difference in genetic background between MZ and DZ affects the susceptibility of the host to virus infection. High acceptance of KP (84.2%) in our study implied a high motivation for treatment for twins with BA. Delays of KP (78 days) in affected twin may be related to the postnatal gradual onset and the late diagnosis.

Circular RNA CCDC66 targets DCX to regulate cell proliferation and migration by sponging miR-488-3p in Hirschsprung's disease.

It has been suggested that circular RNAs play critical roles in natural growth and disease development. Nevertheless, whether the circular RNAs were related in Hirschsprung's disease (HSCR) remains unknown. Thus, we discovered the cir-CCDC66 was downregulated in HSCR compared with the normal gut tissues. The cir-CCDC66 reduction might inhibit cells' proliferation and migration in vitro. Then, we found that DCX transcript was putative cir-CCDC66 competing endogenous RNA. Furthermore, the function of cir-CCDC66 as a sponge for miR-488-3p to regulate DCX RNA expression was demonstrated by immunoprecipitation and luciferase reporter assays. In conclusion, this is the first report revealing that cir-CCDC66 modulates DCX expression through sponging miR-488-3p and thus participates in the onset of HSCR.

Feasibility and efficacy of home rectal irrigation in neonates and early infancy with Hirschsprung disease.

PURPOSE: A single-stage pull-through (SSPT) is the most commonly performed procedure for Hirschsprung disease (HSCR) and has been shown to be better than multi-stage procedures. However, performing a SSPT in the neonatal period or early in infancy is a risk factor for an inaccurate diagnosis, post-operative enterocolitis, and a protracted post-operative recovery. The present study was primarily designed to evaluate the feasibility and efficacy of home rectal irrigation in the neonatal period and early in infancy, followed by a delayed and planned SSPT in a prospective cohort with HSCR. METHODS: Between January 2014 and December 2016, a total of 147 neonates diagnosed with HSCR were enrolled in the study. Six patients were excluded as a result of ganglion cells found in second rectal biopsies after the neonatal period. One hundred twenty-two patients successfully underwent 2-4 months of home rectal irrigation during the neonatal period, followed by a SSPT procedure after the neonatal period (group A, n = 122). Nineteen patients were not candidates for home rectal irrigation, and thus, colostomies were performed during the neonatal period followed by multi-stage procedures after the neonatal period (group B, n = 19). One hundred twenty-two healthy children, age- and gender-matched to group A were enrolled as the healthy control group for assessment of nutrition status (group C, n = 122). The birth weight, gender ratio, aganglionic segment, age, and Hirschsprung-associated enterocolitis (HAEC) score at the time of HSCR diagnosis were measured to evaluate the feasibility of home rectal irrigation in neonates and early in infancy. The nutritional indices, including weight, body length, serum albumin, serum prealbumin, serum retinol-binding protein, and incidence of HAEC after 2-4 successful home rectal irrigation, were used to assess the efficacy of home rectal irrigation. Anastomotic strictures or leakage, perianal excoriation, frequency of defecation, and morbidity of post-operative HAEC were recorded to evaluate the beneficial effects to pull through (PT), which were facilitated by home rectal irrigation. RESULTS: Higher HAEC scores and older age at the time of diagnosis of HSCR were associated with group B, compared to group A (4.34 ± 1.25 vs. 11.0 ± 2.56 [t = 18.20, p < 0.05] and 2.8 ± 1.46 days vs. 12.1 ± 5.3 days [t = 16.10, p < 0.05], respectively). The ratio of rectosigmoid HSCR to non-rectosigmoid HSCR was higher in group A than group B (104/18 vs. 4/15 [χ2 = 34.29, p < 0.05]). There were no differences in birth weight, weight at the time of diagnosis of HSCR, and gender ratio between groups A and B. There were no differences in birth weight, birth length, post-home rectal irrigation age, post-home rectal irrigation weight, post-home rectal irrigation length, and post-home rectal irrigation serum albumin between groups A and C (3.47 ± 0.42 kg vs. 3.48 ± 0.40 kg [t = 0.10, p > 0.05], 50.02 ± 0.49 cm vs. 50.05 ± 0.46 cm [t = 0.61, p > 0.05], 98.59 ± 13.34 days vs. 97.83 ± 13.58 days [t = 0.44, p > 0.05], 6.77 ± 0.66 kg vs. 6.97 ± 0.87 kg [t = 1.95, p > 0.05], 61.55 ± 2.14 cm vs. 61.70 ± 2.07 cm [t = 0.59, p > 0.05], and 41.78 ± 2.42 g/L vs. 41.85 ± 2.37 g/L [t = 0.22, p > 0.05], respectively). The rate of HAEC in the period of home rectal irrigation in group A was low; however, the post-home rectal irrigation serum prealbumin level and retinol-binding protein were significantly lower in group A than group C (0.15 ± 0.04 g/L vs. 0.17 ± 0.05 g/L [t = 3.50, p < 0.05] and 22.51 ± 7.53 g/L vs. 30.57 ± 9.26 g/L [t = 7.46, p < 0.05], respectively). There were no anastomotic strictures or leakage after definitive PT performed in group A. The frequency of defecation ranged from 2-6 times per day, 10 patients had perianal excoriation 3 months after PT, and 11 patients had post-operative HAEC during 6 months of follow-up after PT. CONCLUSION: Home rectal irrigation in neonates and early in infancy, followed by a delayed and planned SSPT is feasible and effective in patients with HSCR, and could be beneficial to definitive PT. However, for patients with an extended aganglionic segment, older age, or high HAEC score at the time of diagnosis of HSCR, rectal irrigation maybe not suitable. TRIAL REGISTRATION: This was a prospective comparative study designed to evaluate the effects of home rectal irrigation for facilitating and enhancing recovery after PT, and was registered at Clinical Trials.gov as NCT02776176.

The effects of two mixed intravenous lipid emulsions on clinical outcomes in infants after gastrointestinal surgery: a prospective, randomized study.

BACKGROUND: There are many advantages of a SMOF emulsion (SMOF-lipid), such as liver-protective properties and anti-inflammatory effects. The objective of this study was to compare the clinical outcomes of SMOF-lipid with medium-chain triglycerides (MCT) /long-chain triglycerides (LCT) in infants after intestinal surgery. METHODS: This was a prospective, randomized study. Neonates receiving intravenous nutrient solution, including lipid emulsion after gastrointestinal surgery, were included in this study. The patients were randomly assigned to the SMOF-lipid or MCT/LCT groups. Infants who received intravenous lipid emulsion continuously for > 2 weeks were considered to have completed the study. Differences in weight gain, nutrition indices, alanine transaminase (ALT), aspartate transaminase (AST), and direct bilirubin (DB), and inflammation cytokine markers (interleukin [IL]-6 and tumor necrosis factor [TNF]-α) were measured. RESULTS: The final sample included 160 infants. One hundred fourteen infants received intravenous SMOF-lipid (74) or MCT/LCT (86) > 2 weeks and 46 infants received intravenous SMOF-lipid (22) or MCT/LCT (24) > 4 weeks. There were no significant differences in weight gain, nutrition indices, inflammation cytokine markers, and sepsis between the groups at the end of 2 and 4 weeks; however, in the SMOF group, the ALT, AST, and DB levels were significantly lower than the MCT/LCT group at the end of 4 weeks. CONCLUSION: The mixture and balanced emulsion of SMOF-lipid was well-tolerated in infants who have undergone gastrointestinal surgery, and liver-protective properties were demonstrated following long-term venous nutrition, especially > 4 weeks.

IGF2-derived miR-483-3p associated with Hirschsprung's disease by targeting FHL1.

HSCR (Hirschsprung's disease) is a serious congenital defect, and the aetiology of it remains unclear. Many studies have highlighted the significant roles of intronic miRNAs and their host genes in various disease, few was mentioned in HSCR although. In this study, miR-483-3p along with its host gene IGF2 (Insulin-like growth factor 2) was found down-regulated in 60 HSCR aganglionic colon tissues compared with 60 normal controls. FHL1 (Four and a half LIM domains 1) was determined as a target gene of miR-483-3p via dual-luciferase reporter assay, and its expression was at a higher level in HSCR tissues. Here, we study cell migration and proliferation in human 293T and SH-SY5Y cell lines by performing Transwell and CCK8 assays. In conclusion, the knockdown of miR-483-3p and IGF2 both suppressed cell migration and proliferation, while the loss of FHL1 leads to opposite outcome. Furthermore, miR-483-3p mimics could rescue the negative effects on cell proliferation and migration caused by silencing IGF2, while the FHL1 siRNA may inverse the function of miR-483-3p inhibitor. This study revealed that miR-483-3p derived from IGF2 was associated with Hirschsprung's disease by targeting FHL1 and may provide a new pathway to understand the aetiology of HSCR.

Lipopolysaccharide enhances ADAR2 which drives Hirschsprung's disease by impairing miR-142-3p biogenesis.

Researches over the past decade suggest that lipopolysaccharide is a dominant driver of gastrointestinal motility and could damage the enteric neuron of rat or porcine. However, it remains poorly defined whether LPS participates in Hirschsprung's disease (HSCR). Here, we discovered that LPS increased in HSCR tissues. Furthermore, LPS treatment suppressed the proliferation and differentiation of neural precursor cells (NPCs) or proliferation and migration of human 293T cells. ADAR2 (adenosine deaminase acting on RNA2)-mediated post-transcriptional adenosine-to-inosine RNA editing promotes cancer progression. We show that increased LPS activates ADAR2 and subsequently regulates the A-to-I RNA editing which suppresses the miR-142 expression. RNA sequencing combined with qRT-PCR suggested that ADAR2 restrain cell migration and proliferation via pri-miR-142 editing and STAU1 up-regulation. In conclusion, the findings illustrate that LPS participates in HSCR through the LPS-ADAR2-miR-142-STAU1 axis.

Aberrant expression of LncRNA-MIR31HG regulates cell migration and proliferation by affecting miR-31 and miR-31* in Hirschsprung's disease.

Hirschsprung's disease (HSCR) is a birth defect that causes a failure of the enteric nervous system to cover the distal gut during early embryonic development. Evidence shows that long non-coding RNAs (lncRNA) play important roles in HSCR. The MIR31 host gene (MIR31HG), also known as Loc554202, is a long non-coding RNA (lncRNA), which acts as the host gene of (microRNA) miR-31 and miR-31*. There have been no studies regarding its function in early developmental defects during pregnancy, and its downstream genetic receptors. We report that downregulation of MIR31HG inhibited migration and proliferation in 293T and SH-SY5Y cell lines, by suppressing miR-31 and miR-31*. Moreover, the downregulation of miR-31 and miR-31* enhanced inter-α-trypsin inhibitor heavy chain 5 (ITIH5) and the phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic gamma subunit (PIK3CG), respectively with reductions of cell migration and proliferation in 293T and SH-SY5Y cell lines. In addition, synergistic actions were observed between miR-31 and miR-31* in cell migration and proliferation. Our results demonstrated that the MIR31HG-miR-31/31*-ITIH5/PIK3CG pathway plays a role in the pathogenesis of HSCR.