ER stress and ASK1-JNK activation contribute to oridonin-induced apoptosis and growth inhibition in cultured human hepatoblastoma HuH-6 cells.

Oridonin, the main active component of Rabdosia rubescens, has antitumor activities in experimental and clinical settings. The aims of the current study were to explore the anticancer abilities of oridonin in hepatoblastoma (HB) HuH-6 cells and to investigate the underlying mechanisms. We found that oridonin inhibited HuH-6 cell in vitro growth in a dose- and time-dependent manner. Further, oridonin induced HuH-6 cell apoptosis and G2/M cell cycle arrest. Upon studying the mechanism, we found that oridonin treatment caused endoplasmic reticulum (ER) stress activation. Meanwhile, ER stress inhibitor salubrinal- or inositol-requiring enzyme 1 (IRE-1) shRNA silencing inhibited oridonin's anti-HuH-6 effects, while ER stress inducers thapsigargin (Tg) and tunicamycin (Tm) mimicked oridonin's actions on HuH-6 cells. Oridonin also activated apoptosis signal regulating kinase 1 (ASK1)-c-Jun N-terminal kinase 1 (JNK1) signaling in cultured HuH-6 cells, which was inhibited by IRE-1 silencing. Importantly, the JNK inhibitors suppressed oridonin-induced growth inhibition and apoptosis in HuH-6 cells. In conclusion, our results suggest that oridonin induces growth inhibition and apoptosis in cultured HuH-6 cells involving ER stress and ASK1/JNK signaling pathways, which enhances our understanding of the molecular mechanisms of oridonin in HB management.

Clinical experience in the treatment of children who swallowed multiple magnetic foreign bodies: A report of five cases.

BACKGROUND: Several clinical reports have been published on complications resulting from swallowing multiple magnetic foreign bodies. This study aimed to summarize the clinical experience of managing children who swallowed multiple magnetic foreign bodies. METHODS: We reviewed the clinical records of five children who swallowed multiple magnetic foreign bodies and were admitted to our hospital during June 2012 to June 2014. Details of the patients' presentation, imaging studies, complications and treatment were recorded. RESULTS: All five children suffered from gastrointestinal perforation and intestinal obstruction. The magnetic foreign bodies caused local bowel wall tissue ischemia necrosis and perforation as well as other complications associated with fistula formation. The magnets were finally removed by laparotomy surgery. CONCLUSION: If magnetic foreign bodies cannot be removed by endoscopy, an operation is suggested as soon as possible to avoid serious complications.

Preliminary identification of key miRNAs, signaling pathways, and genes associated with Hirschsprung's disease by analysis of tissue microRNA expression profiles.

BACKGROUND: Hirschsprung's disease (HSCR) is a congenital gut motility disorder of infants, and if left untreated, it is fatal to the affected infants. This study aimed to identify key microRNAs (miRNAs), signaling pathways and genes involved in the pathogenesis of HSCR. METHODS: The miRNA microarray dataset GSE77296 was downloaded. Nine colon tissue samples were available: six from HSCR patients and three matched control samples. Differentially expressed miRNAs (DEMs) were identified after data preprocessing. Target genes of the selected upregulated and downregulated DEMs were predicted. In addition, functional enrichment analyses for the selected DEMs and target genes were conducted. Finally, interaction networks between the DEMs and target genes were constructed. RESULTS: A total of 162 DEMs (73 upregulated and 89 downregulated) were obtained. A total of 2511 DEM-target gene pairs for the 40 selected DEMs were identified, including 1645 pairs for the upregulated DEMs and 866 pairs for the downregulated DEMs. The upregulated DEM miR-141-3p and down-regulated DEM miR-30a-3p were identified as key miRNAs by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and network analyses. Besides, KEGG pathway enrichment analysis revealed that pathways in cancer and the mitogen-activated protein kinase (MAPK) signaling pathway were key pathways. The key genes frizzled class receptor 3 (FZD3) and docking protein 6 (DOK6) were obtained through the DEM-target gene interaction networks. CONCLUSION: Two key miRNAs (miR-141-3p and miR-30a-3p), the MAPK signaling pathway and two key genes (FZD3 and DOK6) were implicated in the pathogenesis of HSCR.

[The relationship between postoperative complication and pathological features of 324 patients with neuronal intestinal malformations].

OBJECTIVE: To investigate the relationship between the morphological features of different types of neuronal intestinal malformations (NIM) and their postoperative complications. METHODS: The data of morphological and clinical features of 324 cases with NIM were analyzed retrospectively. RESULTS: In all 324 patients, 210 cases were Hirschsprung's disease (HD), 38 intestinal neuronal dysplasia (IND), 45 mixed HD/IND, 8 hypoganglionosis, 22 combined HD/hypoganglionosis and 1 immaturity of ganglion cells. The percentages of normal neuron in bowel of different NIM were 88.1%, 24.4%, 18.4%, 4/8, 27.7% and 0/1 in HD, HD/IND, IND, hypoganglionosis, HD/hypoganglionosis and immaturity of ganglion cells respectively. There were totally 46 cases complicated with recurrent postoperative enterocolitis (EC). Incidence of recurrent postoperative EC in HD patients was 6.7% while in IND/HD and IND patients was 35.6% and 28.9%, respectively. Incidences of EC in cases with the residual IND margins and with the normal margins were 38.2% and 8.7%, respectively. Incidence of EC in cases with transanal endorectal pull-through procedure and with transabdominal procedure was 18.0% and 8.3%, respectively. Nine cases underwent another procedure because of severe persistent constipation or EC after operation, including 4 cases HD/IND, 1 case IND, 3 cases HD and 1 case HD/hypoganglionosis. CONCLUSIONS: Neuron distribution is inconsistent with pathology of NIM. Postoperative EC are rare in the patients only with isolated HD. Furthermore, margins with residual IND and transanal endorectal pull-through procedure are risk factors to recurrent EC. However, the extension of excision about IND is uncertain and need further study.

[Comparison between laparoscopic pyloromyotomy and open pyloromyotomy for infants with congenital hypertrophic pyloric stenosis]

OBJECTIVE: To compare the efficacy of laparoscopic pyloromyotomy with open pyloromyotomy in treatment of congenital hypertrophic pyloric stenosis(CHPS). METHODS: Fifteen patients (age 20%ape;90 days, body weight 2.5 approximate, equals 5.0 kg) with CHPS underwent laparoscopic pyloromyotomy (Group I) and 10 patients (age 26 approximate, equals 90 days, body weight 2.8 approximate, equals 4.5 kg) with CHPS underwent open pyloromyotomy (Group II). Ambulatory 24 hr esophageal pH metry and gastroesophageal mamometry were studied in two groups before and after surgery. RESULTS: All patients presented gastroesophageal reflux (GER) before operation and all reflux parameters were significantly decreased after operation (P<0.01). There was no significant difference between two groups in reflux parameters after surgery. Intragastric pressure (GP) significantly reduced in two groups after operation(3.83+/-1.45)mmHg compared with (2.38+/-0.54)mmHg P<0.01 in Group I,(4.52+/-1.96)mmHg compared with (2.38+/-0.72)mmHg P<0.05 in Guoup II). There was no significant difference in lower esophageal sphincter pressure (LESP), lower esophageal sphincter length (LESL) before and after operation in two groups. The mean operative time for Group I was (32+/-19) mins, which was close to that of Group II after an initial trail. Oral feeding was started 6 h postoperatively in Group I, which was earlier than that in Group II. No technical failures and complications in Group I were encountered. One wound infection and dehiscense was seen in Group II. CLUSION: Laparoscopic pyloromyotomy for infantile hypertrophic pyloric stenosis is safe and feasible, which has lesser complication and similar effect of antireflux as open pyloromyotomy.

Congenital duodenal obstruction in neonates: a decade's experience from one center.

BACKGROUND: Congenital duodenal obstruction (CDO) is one of the most common anomalies in newborns, and accounting for nearly half of all cases of neonatal intestinal obstruction. This study aimed to review our single-center experience in managing congenital duodenal obstruction while evaluate the outcomes. METHODS: We conducted a retrospective analysis of the records of all neonates dianogsed with congenital duodenal obstruction admitted to our center between January 2003 and December 2012. We analyzed demographic criteria, clinical manifestations, associated anomalies, radiologic findings, surgical methods, postoperative complications, and final outcomes. RESULTS: The study comprised 287 newborns (193 boys and 94 girls). Birth weight ranged from 950 g to 4850 g. Fifty-three patients were born prematurely between 28 and 36 weeks' gestation. Malrotation was diagnosed in 174 patients, annular pancreas in 66, duodenal web in 55, duodenal atresia or stenosis in 9, preduodenal portal vein in 2, and congenital band compression in 1. Twenty patients had various combinations of these conditions. Presenting symptoms included bilious vomiting, dehydration, and weight loss. X-rays of the upper abdomen demonstrated the presence of a typical double-bubble sign or air-fluid levels in 68.64% of patients, and confirmatory upper and/or lower gastrointestinal contrast studies were obtained in 64.11%. Multiple associated abnormalities were observed in 50.52% of the patients. Various surgical approaches were used, including Ladd's procedure, duodenoplasty, duodenoduodenostomy, duodenojejunostomy, or a combination of these. Seventeen patients died postoperatively and 14 required re-operation. CONCLUSIONS: Congenital duodenal obstruction is a complex entity with various etiologies and often includes multiple concomitant disorders. Timely diagnosis and aggressive surgery are key to improving prognosis. Care should be taken to address all of the causes of duodenal obstruction and/or associated alimentary tract anomalies during surgery.

[Emergency use of extracorporeal membrane oxygenation in pediatric critically ill patients].

OBJECTIVE: The history of clinical application of extracorporeal membrane oxygenation (ECMO) has been more than 30 years. But in China, there were only a few ECMO centers with limited successful cases reported by the end of twentieth century. The high morbidities and mortalities in current pediatric ECMO practice are noted in China. Therefore, it is necessary to review the experience on rescue use of ECMO in critically ill pediatric patients. METHOD: A retrospective analysis was done for patients who had been receiving ECMO treatment to rescue refractory cardiorespiratory failure from different causes in a hospital between July 2007 and May 2011. RESULT: A total of 12 patients were treated with ECMO; 7 of them were male and 5 female, they aged 6 days to 11 years, weighed 2.8 - 35 (17.21 ± 11.64) kg. The underlying causes of cardiorespiratory failure were as follows: two cases with acute respiratory distress syndrome (ARDS) leading to respiratory failure, 4 with failure of weaning from cardiopulmonary bypass, 3 with fulminant myocarditis, 1 with right ventricular cardiomyopathy leading to repeated cardiac arrest, 1 with preoperative severe hypoxemia, and 1 with anaphylactic shock complicated with massive pulmonary hemorrhage and severe hypoxemia. Of the 12 cases, 3 were established ECMO (E-CPR) while underwent chest compression cardiopulmonary resuscitation (CPR). The mean ECMO support time was 151.75 (15 - 572) h. Seven patients (58.33%) were weaned from ECMO, 6 patients (50.00%) were successfully discharged. Six cases had bleeding from sutures, 2 cases with severe bleeding underwent thoracotomy hemostasis, 2 presented with acute renal failure. Infection was documented in 3 cases, hyperbilirubinemia in 2 cases, lower limb ischemia in 1 case, hyperglycemia in 3 cases, disseminated intravascular coagulation in 1 case, membrane lung leakage in 2 cases, systemic hemolysis in 3 cases, oxygenator failure in 2 cases and oxygenator thrombosis in one case. During the follow-up between 6 months and 4.5 years, 5 patients survived with good quality of life, without any documented central nervous system disorders. One case survived with the right lower extremity disorder from ischemic damage. His motor function has been improved following orthopedic operation at one year after discharge. CONCLUSION: ECMO is a justifiable alternative treatment for reversible severe cardiopulmonary failure in critically ill children.

Incidence of pediatric metachronous contralateral inguinal hernia in children aged ≥1 year.

BACKGROUND: The management of the contralateral asymptomatic side when a child with initial unilateral inguinal hernia undergoes herniorrhaphy continues to be controversial. Age less than 6 months at initial herniorrhaphy is considered as a high risk factor of the occurrence of metachronous contralateral inguinal hernia (MCIH). We performed herniorraphy for patients ≥1 year with initial unilateral hernia at one-day-set outpatient-surgery department without any intervention of contralateral groin. In this study, we reviewed the characteristics of development of MCIH in this condition and discuss the management strategies of MCIH. METHODS: The subjects of this study were children who were treated at our outpatient-surgery department from January 2006 to December 2006. A total of 2129 patients with initial unilateral hernia and aged ≥1 year underwent an ipsilateral herniorhhaphy only. Patients were followed up for the development of MCIH to 60 months. The Chi-square test was used for intergroup comparison, a level of P<0.05 was considered as statistically significant. RESULTS: Among these children 1341 (63.0%) were obtained 60 months follow-up data, 1146 (85.5%) were boys and 195 (14.5%) were girls. MCIH developed in 70 (5.2%) patients, 61 were boys and 9 were girls. In 570 patients aged 12-23 months, 43 developed MCIH (7.5%); in 564 patients aged 24-59 months, 21 developed MCIH (3.7%); and in 207 patients ≥60 months, 6 patients developed MCIH (2.9%), the difference between these groups was highly significant (P=0.004). In male patients, 30 right-sided MCIHs occurred after 423 initial left-sided herniorrhaphies (7.1%) and 31 left-sided MCIHs occurred after 723 initial right-sided herniorrhaphies (4.3%), difference between these two groups was significant (P=0.041). Seventy-seven percent of the MCIHs occurred within 1 year, 94% occurred within 2 years after initial herniorraphy. CONCLUSIONS: As the overall incidence of MCIH in patients aged ≥1 year was 5.2%, routine contralateral groin exploration is not suggested. Transinguinal laparoscopy could be considered as an alternative of conventional "wait and see" policy, especially in patients less than 2 years or left-sided initial unilateral inguinal hernia. If "wait and see" policy is adopted, patients should be closely followed up for 2 years.

Laparoscopic cholecystostomy and bile duct lavage for treatment of inspissated bile syndrome: a single-center experience.

BACKGROUND: We aim to describe our experience of laparoscopic cholecystostomy and bile duct lavage in the treatment of inspissated bile syndrome. METHODS: Between January 2005 and December 2009, 16 infants with inspissated bile syndrome underwent laparoscopic cholecystostomy and bile duct lavage in our department. They were 7 males and 9 females, aged 40 days to 3 months, with an average of 65±23.4 days. A laparoscopic aided cholecystostomy was done. Cholangiography and bile duct lavage were performed during the operation. One week after the operation, bile duct lavage with saline was repeated every 2 to 3 days. According to bilirubin levels and liver function, the tube was kept for 2-4 weeks. RESULTS: The level of bilirubin decreased and liver function was greatly improved after bile duct lavage. Direct bilirubin level, aspartate aminotransferase and γ-GT were significantly decreased 1-2 months after the operation compared with those before surgery (P<0.05). CONCLUSIONS: The treatment strategy for inspissated bile syndrome with laparoscopic cholecystostomy and biliary duct lavage is feasible and effective.

Pinacidil improves contractile function and intracellular calcium handling in isolated cardiac myocytes exposed to simulated cardioplegic arrest.

BACKGROUND: We examined the effects of pinacidil on contractile function and intracellular calcium in isolated rat cardiomyocytes exposed to cardioplegic solution. METHODS: Rat myocytes were incubated at 24 degrees C for 2 hours in cardioplegic solution with or without pinacidil (50 micromol/L), then they were perfused with Krebs-Henseleit solution with a gas phase of 95% O2/5% CO2 at the same temperature. Contraction and intracellular calcium transients were then measured by video tracking and spectrofluorometry. RESULTS: During 20 minutes of perfusion after 2 hours in cardioplegic solution with pinacidil, (1) the recovery of contractile function was significantly increased in terms of both amplitude of contraction (98.30% +/- 9.90% versus 81.00% +/- 11.25%; p < 0.05) and peak velocity of cell shortening (100.90% +/- 13.79% versus 76.89% +/- 18.14%; p < 0.01) when compared with myocytes in cardioplegic solution without pinacidil; (2) the amplitudes of the intracellular calcium transients evoked by electrical stimulation and caffeine (10 mmol/L) increased by 23.31% to approximately 40.72% and 61.73%, respectively, compared with those in cardioplegic solution without pinacidil; and (3) the decay time of the caffeine-induced intracellular calcium transient decreased by 36.64% +/- 15.10% relative to that measured in cardioplegic solution without pinacidil. The effects induced by supplementing the cardioplegic solution with pinacidil were diminished in the presence of glibenclamide (10 micromol/L). CONCLUSIONS: Addition of the adenosine triphosphate-sensitive potassium-channel opener, pinacidil, to a high potassium cardioplegic solution improves recovery of contractile properties and cytosolic calcium in isolated rat cardiac myocytes.