Effectiveness of WeChat-group-based parental health education in preventing unintentional injuries among children aged 0-3: randomized controlled trial in Shanghai.

BACKGROUND: Unintentional injuries to children are a major public health problem. The online social media is a potential way to implement health education for caregivers in online communities. Using WeChat, a free and popular social media service in China, this study evaluated the effectiveness of social online community-based parental health education in preventing unintentional injuries in children aged 0-3. METHODS: We recruited 365 parents from two community health centers in Shanghai and allocated them into intervention and control groups randomly. Follow-up lasted for one year. The intervention group received and followed their WeChat group and a WeChat official account for dissemination of reliable medical information. The control group received only the WeChat group. RESULTS: Between the intervention and control groups, changes in unintentional injuries (OR = 1.71, 95% CI: 1.02-2.87, P = .04), preventability (ß = 0.344, 95% CI: 0.152-0.537, P < .001), daily supervision behavior (ß = 0.503, 95% CI: 0.036-0.970, P = .04), and behaviors for preventing specific injuries (ß = 2.198, 95% CI: 1.530-2.865, P < .001) were significantly different, and change in first-aid skills for treating a tracheal foreign body were nearly significant (P = .06). CONCLUSIONS: The WeChat-group-based parental health education can reduce the occurrence of unintentional child injuries by improving parents' skills, beliefs, and behaviors. Online social communities promote health education and reduce unintentional injuries among children. TRIAL REGISTRATION: ChiCTR1900020753. Registered on January 17, 2019.

Epidemiology of unintentional injury in children admitted to ICU in China mainland: a multi-center cross-sectional study.

Background: To investigate the epidemiology of unintentional injury in children admitted to Intensive Care Unit (ICU) in China mainland. Methods: A total of 39 hospitals in 19 provinces contributed to the 1-day point prevalence study of serious unintentional injury in children aged 0-16 years admitted to ICU. Results: A total of 1,017 patients from the 39 participating ICUs on the study day were included. Among them, 56 pediatric patients were identified to be suffered from unintentional injury from 18 participating ICUs, accounting for 5.5% (56/1,017) of all the ICU patients. The percentage of boys was more than twice the percentage of girls. Most patients had an age of less than 6 years old (n=42, 75%). The leading cause of unintentional injury was fall (n=17, 30.4%). The patterns of unintentional injury in children were age-related. There were no urban-rural differences in our cohort. The injury happened on 12:00-18:00 PM in 27 cases (48.2%), and 28 patients (50%) had injuries happened at working day. 35 patients (62.5%) received primary treatment at local hospitals. Thirty-five patients (62.5%) needed resuscitation in the emergency department, 15 patients (26.8%) still needed resuscitation in ICU. These 56 children suffered from a total of 106 lesions corresponding to 1.89 lesions per patient. Respiratory failure was most commonly seen (n=18, 32.1%). There was no death in our cohort during the study. After effective treatment during their ICU stay, 45 (80.4%) patients showed improvement, with Glasgow Coma Scale (GCS), Pediatric Trauma Score (PTS) and Pediatric Risk of Mortality III (PRISM III) score significantly better than those before treatment (P<0.05). Conclusions: Higher injury rates among children under 6 years old of age illustrate the need for preventive measures, especially programs and public policies targeting this high-risk group.

Expression Profiles of Exosomal MicroRNAs Derived from Cerebrospinal Fluid in Patients with Congenital Hydrocephalus Determined by MicroRNA Sequencing.

Purpose: Congenital hydrocephalus is one of the most common birth defects worldwide. Exosomal microRNAs (miRNAs) in body fluids have been implicated in many diseases. However, their involvement in cerebrospinal fluid from congenital hydrocephalus is not well understood. This study is aimed at investigating the role of dysregulated exosomal miRNAs in congenital hydrocephalus. Methods: We collected cerebrospinal fluid samples from 15 congenital hydrocephalus patients and 21 control subjects. We used miRNA sequencing to generate exosomal miRNA expression profiles in three pairs of samples. We identified 31 differentially expressed exosomal miRNAs in congenital hydrocephalus and predicted their target mRNAs. Results: Three microRNAs (hsa-miR-130b-3p, hsa-miR-501-5p, and hsa-miR-2113) were selected according to their fold changes and the function of their target mRNAs, and only hsa-miR-130b-3p and hsa-miR-501-5p were confirmed their expression levels in all samples. Moreover, upregulated hsa-miR-130b-3p might mediate the downregulation of the phosphatase and tensin homolog gene (PTEN), which has been associated with hydrocephalus, via binding to its 3'-untranslated region by dual-luciferase reporter assay. Conclusion: This study implicates that abnormally expressed exosomal miRNAs in cerebrospinal fluid may be involved in the pathomechanism of congenital hydrocephalus.

PHOX2B as a Reliable Marker for Neuroblastoma in Tissue and Cytology Specimens.

To investigate the diagnostic utility of immunohistochemistry for paired-like homeobox 2B (PHOX2B) expression in neuroblastomas (NBs) and tumors that mimic them, tissue samples (n = 229) from 157 cases of NB, 210 central nervous system tumors, and 170 extracranial non-NB solid tumors (n = 170) were immunostained for PHOX2B. Additionally, PHOX2B expression in 67 body fluid cytology specimens was analyzed. In tissue specimens, PHOX2B expression was positive in NBs, pheochromocytomas, and paragangliomas but negative in all of the other tumors evaluated. PHOX2B was detected by immunohistochemistry in 5 NB cytology specimens; all of the others were negative. These results suggest that PHOX2B may be a sensitive and specific immunohistochemical marker for the pathological diagnosis and differential diagnosis of NB in both tissue and cytology specimens.

Parents' attitudes as mediators between knowledge and behaviours in unintentional injuries at home of children aged 0-3 in Shanghai, Eastern China: a cross-sectional study.

OBJECTIVE: Parental behaviours are important in preventing unintentional injury at home among young children. Previous research showed an inconsistent relationship between knowledge and behaviours, indicating that the mechanisms may vary for different behaviours. This study aimed to examine the mediating roles of different attitudes in the mechanism of knowledge acting on different behaviours. DESIGN: Cross-sectional study. SETTING: Eastern China. PARTICIPANTS: Participants were recruited using stratified community-based sampling. A total of 488 parents of children aged 0-3 years participated in the study and 476 (97.5%) valid questionnaires were recovered. PRIMARY OUTCOME MEASURES: Parents' knowledge, attitudes (including injury attribution, preventability and responsibility) and behaviours (including supervision behaviours, risky behaviours and providing a safe home environment). RESULTS: The results of mediation analysis showed that the mediator variables were different for different behaviours and that all associations were positive. Parents' knowledge (ß 0.19, 95% CI 0.13 to 0.24) and attitude of injury attribution (ß 0.37, 95% CI 0.21 to 0.46) were directly associated with risky behaviours. Attitude of preventability was directly associated with parents' supervision behaviour (ß 0.27, 95% CI 0.14 to 0.40). Parents' attitude of preventability mediated the positive association between knowledge, attitudes of injury attribution and responsibility, and supervision behaviours, as well as providing a safe home environment. In addition, the occurrence of child injuries at home was directly associated with home environment (ß -0.41, 95% CI -0.82 to -0.01). CONCLUSIONS: The current findings confirm that attitudes play varying mediating roles between knowledge and different behaviours. An important recommendation is that parents' attitudes, especially towards preventability and responsibility, need to be considered when health providers develop health education programmes targeted at improving parental supervision behaviours and providing a safe home environment.

Causes and Characteristics of Children Unintentional Injuries in Emergency Department and Its Implications for Prevention.

Background: Child unintentional injuries have become a hot topic worldwide, and substantial regional disparities existed in causes and characteristics. To date, limited data are available to investigate the causes and characteristics of child unintentional injuries from hospitals for children in China. Methods: A cross-sectional study was conducted between January 2017 and December 2018 in Shanghai, China. Patients aged <18 years with an unintentional injury presented to the emergency department were enrolled. Demographic information, Pediatric Risk for Mortality III score, and outcome variables were retrieved from electronic health records (EHRs). Frequencies and proportions of categorical variables and means and SDs of continuous variables are presented. Chi-square test and Student's t-test were used for the comparison between groups, as appropriate. Logistic regression analysis was used to estimate potential risk factors for admission to the hospital. Results: A total of 29,597 cases with unintentional injuries were identified between January 2017 and December 2018, with boys vs. girls ratio of 1.75. Preschool children account for approximately two-thirds of unintentional injuries in the emergency department. A distinctive pattern of mechanisms of unintentional injuries between gender was documented, and sports injury was significantly higher in boys than in girls (10.2 vs. 7.8%). Compared with Canadian Emergency Department Triage and Acuity Scale (CTAS) Grade 3 patients, Grade 2 [odds ratio (OR) = 2.99, 95% CI = 1.93-4.63, P < 0.001] and Grade 1 (OR = 74.85, 95% CI = 12.93-433.14, P < 0.001) patients had higher risk of inhospital admission. For causes of injuries, compared with falling, foreign body and poison had a lower risk of inhospital admission, while transport injury (OR = 1.31, 95% CI = 1.07-1.59, P = 0.008) and high fall injury (OR = 2.58. 95% CI =1.48-4.49, P < 0.001) had a significantly higher risk of admission. Conclusions: There was a significant relationship between age-groups and unintentional injuries between gender, with decreased injuries among girls growing up older. Preventive measures should be taken to reduce transport injury and high fall injury, which had a significantly higher risk of admission.

Predictor of a permanent shunt after treatment of external ventricular draining in pediatric postinfective hydrocephalus-a retrospective cohort study.

PURPOSE: To assess the therapeutic efficacy of external ventricular draining (EVD) and to predict the need for permanent shunts in infants with postinfective hydrocephalus (PIHC). METHODS: This is a retrospective study of infants diagnosed with PIHC and treated by EVD between January 2013 and December 2017 at the Children's Hospital of Fudan University. Clinical, laboratory, and imaging data were collected and analyzed to identify independent risk factors by logistic regression analyses. The predictor was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curves. RESULTS: In total, 48 patients were identified, and 31 cases (64.5%) had a permanent shunt. EVD was effective in accelerating cerebrospinal fluid purification. In the permanent shunt group, the duration of EVD was significantly longer (28.5 ± 5.2 vs 14.9 ± 3.0 P < 0.05) and the frontal and occipital horn ratio (FOHR) at 7-10 days after EVD was significantly higher (0.57 ± 0.01 vs 0.48 ± 0.01 P < 0.001). The FOHR at 7-10 days after EVD predicts the need for a permanent shunt with an area under the ROC curve of 0.818. CONCLUSION: EVD was effective for purification of CSF, whereas a permanent shunt was needed for more than half of the patients. The FOHR at 7-10 days after EVD may be a strong predictor for a permanent shunt.

RBM5 Acts as Tumor Suppressor in Medulloblastoma through Regulating Wnt/ß-Catenin Signaling.

INTRODUCTION: RBM5 acts as a tumor suppressor gene in lung and breast cancers; however, its role in the pathogenesis of medulloblastoma (MB) remains unclear. We previously identified 4 RBM5 mutations in whole exome sequencing analysis of 40 MB patients. This study examined the role of RBM5 in MB progression. METHODS: The expression patterns of RBM5 in tissues of 40 MB patients were analyzed using immunohistochemistry. Associations between RBM5 expression and overall survival (OS) were evaluated using Kaplan-Meier analysis. The RBM5 role in Daoy cells' proliferation, migration, and Wnt/ß-catenin signaling was analyzed after RBM5 knockdown and overexpression. RESULTS: The expression level of RBM5 mRNA and protein was significantly lower in MB than that in adjacent normal control tissues, and low RBM5 expression was significantly associated with reduced OS (p = 0.034). RBM5 knockdown induced Daoy and ONS-76 cells proliferation, while RBM5 overexpression repressed cell proliferation and migration in vitro (all p < 0.05). ß-Catenin, LEF1, and cyclin D1 mRNA levels were upregulated, while DKK1 expression was downregulated in Daoy cells following RBM5 knockdown. CONCLUSION: RBM5 may function as a tumor suppressor in MB by regulating Wnt/ß-catenin signaling, and its reduced expression is associated with lower OS.

Neuroblastomas in Eastern China: a retrospective series study of 275 cases in a regional center.

PURPOSE: Most studies on neuroblastoma (NB) have been conducted in Western countries or Japan. The objective of our study was to analyze clinical and pathological features, MYCN status, surgical methods, and prognosis in Chinese NB patients. METHODS: A retrospective, single-center case series study of 275 NBs was implemented. Clinical manifestations, pathological features, MYCN status, and surgical treatment were analyzed. Log-rank test and Cox hazards models were used to assess overall survivals (OSs). RESULTS: The cohort consisted of 105 females and 170 males, with an age range of five days to 15 years. MYCN amplification was detected in 21.5% of all cases. The median OS was 15.0 months for MYCN amplified group. The five-year OS rates were 70.8% and 18.3% for MYCN unamplified and amplified groups, respectively, and the comparison of Kaplan-Meier curves for these two groups showed statistical significance (P < .001 by log-rank test). Gross total resection (GTR, n = 111) and subtotal resection (STR, n = 58) were administered in 169 patients at stages 3 and 4 who received chemotherapy and the comparison of Kaplan-Meier curves for different groups in these patients had statistical significance (STR vs. GTR, P = .009; MYCN unamplified vs. amplified, P < .001 by log-rank test, respectively).The multivariate survival analyses showed statistical significance (STR vs. GTR, P = .047; MYCN unamplified vs. amplified, P = .001 by Cox regression model). CONCLUSIONS: MYCN amplification is an independently adverse prognostic factor in Chinese NB patients at stages 3 and 4 and GTR is associated with improved OS compared with STR in these patients.

Ectopic nephrogenic rests in children: A series of 13 cases in a single institution.

PURPOSE: Ectopic nephrogenic rests (ENR) are extremely rare, and their diagnosis and treatment have not yet been standardized. Our study aimed to analyze the clinical and pathological features of ENR in children and explore the optimal methods for diagnosis and treatment. METHODS: A retrospective, single-center, case series study of 13 children with ENR was performed. Clinical manifestations, work-up, pathological features, and treatment methods were analyzed, and the postoperative status was evaluated at follow-up. RESULTS: The study cohort included seven males and six females aged 1/4-19 months, who were divided into two subgroups: group 1 (pure ENR, cases 1-3) and group 2 (ENR associated with teratoma, cases 4-13). The patients commonly presented with a painless mass or an incidental finding in surgery. The ENR were detected in the lumbosacral and sacrococcygeal region (five cases), retroperitoneal area (five cases), testis (one case), gubernaculum testis (one case), and stomach (one case). Radiological findings showed a mixed-density mass or a mixed-signal-intensity lesion in group 2. All the patients underwent surgical resection, and all except two were event-free in a follow-up period of 2-154 months. Case 8 showed recurrence, and extended surgery was performed. Case 7 developed metastases and received chemotherapy. CONCLUSIONS: ENR are rare among children and have no specific clinical manifestations, lab tests, and radiological features. Different treatment strategies may be adopted based on the diagnosis. Complete resection can generally be achieved, and the prognosis is excellent in most cases. However, relapse or metastasis may occur in a small subset of patients. Close follow-up is mandatory to detect recurrence and metastasis early.

Melanotic neuroectodermal tumor of infancy in the soft tissue of the forearm: report of a case.

Melanotic neuroectodermal tumor of infancy is rare. Only 3 cases have been reported in the soft tissue of the extremities up to date. It has a typically biphasic feature in morphology. Epithelial and melanotic markers are positive in the epitheliod cells and neuron-specific enolase or synaptophysin is positive in the small blue round cells in immunohistochemistry. Radical resection and close follow-up is the treatment strategy in general situation. Here we report one case of MNTI in the upper extremity with review of the literature. This is the first case of MNTI in the forearm.

SOX2 promotes tumorigenicity and inhibits the differentiation of I-type neuroblastoma cells.

SOX2 is a transcription factor associated with the pluripotency, proliferative potential, and self-renewing properties observed with embryonic stem cells and germ cells. SOX2 expression has been reported in several cancers and is implicated in tumorigenesis. We previously found that SOX2 expression was correlated to the clinical stage of neuroblastoma. Recently, we found that SOX2 overexpression occurs in I-type neuroblastoma cells (BE(2)-C cells). To elucidate the tumorigenic function of SOX2, we established a SOX2 overexpressed BE(2)-C cell line. SOX2 overexpressed cells showed higher tumorigenicity than control cells and exhibited decreased expression levels of marker proteins of N- or S-type cells after agent-induced differetiation. By contrast, in cells where SOX2 mRNA expression was knocked down by gene-specific siRNA, tumorigenicty was significantly decreased and the expression levels of marker proteins of N- or S-type cells were upregulated. In conclusion, our findings indicate an important function for SOX2 in promoting tumorigenicity of I-type neuroblastoma cells and in inhibiting their differentiation, suggesting that SOX2 might be a potential therapeutic target in neuroblastoma.

Image-guided prediction of pseudocyst formation in pediatric pancreatic trauma.

BACKGROUND: To determine if there is an effective alternative to the current standard of computed tomography (CT) grading of pediatric pancreatic injuries. We hypothesized that the Wong grading scale, which is based on the depth and location of the pancreatic laceration, is more predictive of pseudocyst formation than the American Association for the Surgery of Trauma (AAST) scale after nonoperative management of traumatic pancreatic injury in children. MATERIALS AND METHODS: A retrospective review of children admitted for pancreatic trauma to two level 1 pediatric trauma centers between 2000 and 2012 was conducted. Patients who underwent primary operation were excluded. Initial CT scans were reviewed by two radiologists blinded to clinical outcomes, and injury grades from both scales were assigned. The primary outcome was pseudocyst formation. RESULTS: Fifty-three patients (ages 7 mo-17 y) were included. As per the Wong scale, pseudocysts occurred in 0/20 patients with grade A injuries, 2/17 (12%) with BI/CI injuries, and 9/15 (60%) with BII/CII injuries. Using the AAST scale, pseudocysts developed in 2/27 (7%) patients with grade I/II injuries, 7/20 (35%) patients with III/IV/V injuries, and 1/6 (17%) patients with a scan that was indeterminate between grades II and III. Positive Predictive value, negative predictive value, sensitivity, and specificity for pseudocyst formation were all higher using the Wong scale (AAST/Wong: Positive Predictive value 42%/50%, negative predictive value 91%/94%, sensitivity 80%/82%, and specificity 65%/77%). CONCLUSIONS: The Wong CT grading scale may be superior to the AAST scale for early risk stratification for pseudocyst development after nonoperative management of pediatric pancreatic trauma; however, a larger study is needed for verification of these findings.

Gastroblastoma in a 12-year-old Chinese boy.

Gastrablastoma is a rare epitheliomesenchymal biphasic tumor of stomach in children and young adults first reported by Miettinen et al in 2009. Five cases have been reported up to date including only one case with the nodal metastasis and distant metastases. With little atypism gastroblastoma is suggested to be a low-grade malignancy. Here we report one case of gastroblastoma in a 12-year-old boy with review of the literature. This is the first case of gastroblastoma in Chinese to our knowledge.

Endoscopic-assisted surgery for pyriform sinus fistula in children: experience of 165 cases from a single institution.

BACKGROUND: Congenital pyriform sinus fistula (PSF) is relatively rare, but often presents diagnostic and therapeutic challenges. Herein, we report our experience of endoscopic-assisted surgery of PSF in children. METHODS: Since 1999, 165 children (100 males, 65 females) with PSF had been enrolled. Their clinical manifestations were recurrent lateral neck infection, cervical mass and respiratory distress. Preoperative investigations included barium swallow, ultrasound, computed tomography, and thyroid scan. After resolution of the infection, the fistulas were identified by the endoscopic-assisted technique at operation. The fistula tract was completely excised just at the apex of the pyriform sinus. More recently, the anatomic point where the fistula tract penetrated into the pharynx was specified and recorded. RESULTS: Of the 165 cases, the male to female ratio was 1.54:1, the median age of onset was 3.2 years (range, 1 day to 13.8 years), and median age at operation was 5.0 years (range, 17 days to 15.0 years). One hundred fifty-six (94.6%) fistulas located on the left side, 7 right, and 2 bilateral. Twelve neonates and young infants (younger than 3 months) presented with a large cervical cyst. The fistulas were completely excised in all but 2 (98.8%) with intraoperative gastroscopy successfully conducted in 160 cases (97.0%). In 77 cases the points where fistulas penetrated into the pharynx were specified intraoperatively, which were classified into 3 types according to their anatomic relationship with the inferior cornu of the thyroid cartilage (ICTC): type I (anterior to ICTC), 22 cases (28.5%); type II (inferior to ICTC), 18 cases (23.4%); and type III (posterior to ICTC), 37 cases (48.1%). Postoperatively, 160 cases recovered well without complications. PSF recurred in 5 cases, 2 of whom were cured by fistula re-excision and 3 remained asymptomatic. Esophageal perforation was found and repaired uneventfully in 1 neonate and 1 young infant. Transient postoperative hoarseness happened in 1 neonate. All the latter 3 cases had cervical cysts. CONCLUSIONS: To our knowledge, this series is the largest report of PSF in children. Our results suggested that PSF is more common in males. With the help of endoscopy and a better understanding of the anatomic relationship between ICTC and the points where the fistulas penetrated into the pharynx, PSF excision can be done successfully with minimized complications. For neonates and young infants with a cervical cyst, however, the management of PSF continues to be a challenge.

Sacrococcygeal teratoma with nephroblastic elements: a case report and review of literature.

Sacrococcygeal teratoma with nephroblastic elements is very rare. Only 8 cases have been reported up to date. 3 cases were misdiagnosed as extrarenal nephroblastomas and were administered excessive treatments such as chemotherapy and radiation therapy. It has a great significance to distinguish sacrococcygeal teratoma with nephroblastic elements from extrarenal nephroblastoma for their different biological behaviors, therapies and prognoses. Here we report one case of sacrococcygeal teratoma with nephroblastic elements in a newborn with review of the literature. This is the first case of sacrococcygeal teratoma with nephroblastic elements in Chinese to our knowledge.

Antiangiogenic effect of propranolol on the growth of the neuroblastoma xenografts in nude mice.

BACKGROUND: Propranolol has been reported to display an antiangiogenic effect on infantile hemangiomas and also some adult cancers. Little is known, however, about whether propranolol has such effect on pediatric malignancies. METHODS: Nude mice bearing BE(2) C neuroblastoma xenografts were injected intraperitoneally with propranolol and divided into groups of PROP-2 (n=11), -5 (n=11), and -10 (n=10) according to the treating dosages of 2, 5, and 10 mg kg(-1) day(-1), respectively. The tumor volume and body weight were recorded every other day. All mice were sacrificed on day 9, and the levels of angiogenic factors were measured in harvested xenografts by immunohistochemistry and western blotting. RESULTS: The tumor volume and weight of PROP-2 (0.72±0.28 cm(3), 0.59±0.21 g) and PROP-5 (0.81±0.35 cm(3), 0.61±0.25 g) were significantly decreased when compared with those of CTL (1.22±0.58 cm(3), 0.93±0.15 g; P<0.01). The tumor microvessel density (MVD) scores that PROP-2, -5, and -10 groups had (49.28±17.53, 52.45±17.11, and 51.09±13.18 pixels per picture, respectively) were lower than those from the control group (65.29±17.33 pixels per picture, P<0.01). Furthermore, vascular endothelial growth factor (VEGF), metalloproteinase-2 (MMP-2), and metalloproteinase-9 (MMP-9) levels were significantly lower in the groups with propranolol treated dosage of 5 and 10 mg kg(-1)day(-1) than in the control group. CONCLUSIONS: Propranolol can exhibit an inhibitory effect on the tumor growth and angiogenic factors expression in neuroblastoma xenografts, which may provide some knowledge to the role of ß-blockers in the management of NB.

Genistein inhibits estradiol- and environmental endocrine disruptor-induced growth effects on neuroblastoma cells in vitro.

The aim of this study was to examine the effect of genistein on human neuroblastoma cell proliferation induced by two common environmental endocrine disruptors, bisphenol A (BPA) and Di-2-ethylhexyl phthalate (DEHP), and to investigate its underlying mechanism. SK-N-SH human neuroblastoma cells were treated with E2 (1 ng/ml), BPA (2 µg/ml) or DEHP (100 µM), with or without genistein (12.5 µM) in vitro. The number of viable cells was detected with an absorbance reader after 0, 24, 48 or 72 h treatment. The percentage of cells in different phases, and expression of Akt and its phosphorylation levels were also assessed by flow cytometry and western blot analysis at 72 h, respectively. The BPA and DEHP groups had a 30% higher number of viable cells compared to the non-treated group at 48 h (P<0.001). However, the cell numbers did not increase significantly in the groups with additional treatment with genistein (P>0.05 vs. control) and the same trend was observed at 72 h. The expression of phospho-Akt protein was increased in the groups treated with BPA or DEHP compared to the control group at 72 h (P<0.05), while no significant elevation in the expression of phospho-Akt was observed (P>0.05) in genistein-treated groups. Cells were arrested at the G2/M phase by genistein. Similar effects were observed in the E2 group with or without genistein treatment. Akt protein expression had no significant change among all the groups (P>0.05). In conclusion, estradiol- or environmental endocrine disruptor-induced proliferation of human neuroblastoma cells is effectively abolished by genistein, likely in a cell cycle- and Akt pathway-dependent manner.

Downregulation of OCT4 promotes differentiation and inhibits growth of BE (2)-C human neuroblastoma I-type cells.

In in vitro continuous culture, N (neuroblastic)-, S (substrate adherent)- and I (intermediate)-type cells were identified in human neuroblastoma (NB), where I-type is recognized as a stem cell type. Octamer-binding protein 4 (OCT4) is a cell marker used to identify the stemness of cells, whose roles in regulating I-type NB cells have yet to be fully elucidated. In the present study, we assessed the differentiation regulation role of OCT4 in BE (2)-C of I-type cells. We demonstrated that downregulation of OCT4 expression in BE (2)-C was associated with reduced cell proliferation and loss of colony formation ability on soft agar, and prompted BE (2)-C cells to differentiate to S-type cells. By contrast, overexpression of OCT4 increased cell proliferation and colony formation ratio, but no obvious differentiation promotion was observed. Furthermore, induced differentiation of BE (2)-C cells to S-type by 5-bromo-2'-deoxyuridine (BrdUrd) was accompanied by reduced expression of OCT4.