Saturation compensation for visible light communication with off-the-shelf detectors.

A photodetector may get saturated if the incident optical power approaches the detector saturation threshold. In such a case, a visible light communication (VLC) system fails to recover the useful transmitted signals. We introduce a saw waveform based response characterization technique when an off-the-shelf avalanche photo-diode (APD) is deployed. Subsequently, we present two saturation compensation methods, namely the optical attenuation and gain reduction. We analytically conclude that the latter outperforms the former in terms of signal to noise ratio. Experimental results demonstrate the effectiveness of the proposed methods in improving the bit error rate (BER) and error vector magnitude (EVM) performances in the presence of strong ambient radiation and detector noise. In addition, optimization of the APD internal gain and joint employment of the two compensation methods are discussed.

Graph-based multi-user scheduling for indoor cooperative visible light transmission.

Recent progress in the indoor visible light communication (VLC) has shown promising signs of alleviating an increasing strain on the radio frequency spectrum and enhancing transmission capacity. Nevertheless, the indoor VLC usually suffers from inter-channel interference (ICI) due to the dense light-emitting diode (LED) deployment. The ICI is considered as a key factor affecting signal to interference and noise ratio (SINR) and spectral efficiency. To address this challenge, an efficient multi-user scheduling framework that employs interference coordination and cooperative transmission is investigated based on the graph theory. To effectively mitigate ICI and maximize benefit of the cooperative transmission, the cell-centric (CC) and user-centric (UC) clustering are introduced for cooperative transmission. For the CC clustering, the multi-user scheduling problem under the proportional fairness criterion is formulated to maximize spectral efficiency while ensuring user fairness. Such a problem is solved by linear programming and greedy algorithms after transforming it into a maximum weighted independent set problem with the aid of a modified interference graph. For the UC clustering, the multi-user scheduling problem under the max-min criterion is formulated and solved by a proposed heuristic approach based on the bipartite graph theory. Numerical results show that the proposed graph-based scheduling is capable of providing up to 7.7 dB gain in SINR over the non-cooperative transmission. The bipartite graph scheduling offers high spectral efficiency and service fairness index. In the worst case with an occlusion probability of 1, a small SINR penalty of up to 1 dB is observed with the greedy algorithm. It is shown that the graph-based scheduling is robust to receiver rotation and occlusion in terms of spectral efficiency, SINR, and user fairness.

Comparison of interpolation-based sampling frequency offset compensation schemes for practical OFDM-VLC systems.

Sampling frequency offset (SFO) is an important issue in the orthogonal frequency-division multiplexing (OFDM)-based visible light communication (VLC) systems with low-cost analog-to-digital or digital-to-analog converters (ADCs/DACs). A digital interpolation or resampling filter can be used to effectively compensate the SFO. In such case, oversampling at the receiver ADC is required to mitigate the aliasing effect due to imperfect DACs and nonlinearity of visible light sources that cause extra frequency components inside/outside the OFDM signal spectrum. The oversampling factor (rate) is mainly determined by the order of the digital interpolation filter and nonlinear VLC links. The design of the OFDM-VLC receiver incorporating the digital interpolation filter is vital as it affects not only the transmission performance but also the complexity of digital signal processing (DSP). To evaluate the feasibility of the digital interpolation-based SFO compensation schemes for cost-sensitive VLC applications, in this paper, a real-time OFDM-VLC receiver incorporating the 2nd/3rd/4th order interpolation filters is experimentally demonstrated. An OFDM frame structure is designed for the synchronization including SFO estimation and compensation, in which the precision and latency of DSP are considered. On the basis of the real-time OFDM-VLC receiver, the comparison in the VLC transmission performance and DSP complexity between different interpolation-based SFO compensation schemes is discussed.

BMP2 Is Related to Hirschsprung's Disease and Required for Enteric Nervous System Development.

The enteric nervous system (ENS) is derived from neural crest cells (NCCs). Defects in ENS NCCs colonizing in the intestines lead to an absence of enteric ganglia in the colon and results in Hirschsprung's disease (HSCR). Bone morphogenetic proteins (BMPs) play diverse roles in the proliferation, migration and survival of ENS NCCs; however, whether BMPs are involved in HSCR and the underlying mechanism remains largely unknown. In this study, we found that BMP2 expression is significantly decreased in HSCR patients. Further experiments demonstrated that BMP2 is involved in the regulation of NCC proliferation, migration and differentiation. In a detailed analysis of the role of BMP2 in HSCR development in vivo, we demonstrated that BMP2b regulates the proliferation, migration and differentiation of vagal NCCs in zebrafish and that BMP2b is required for intestinal smooth muscle development. In addition, we showed that BMP2b is involved in regulating the expression of glial cell line-derived neurotrophic factor (GDNF) in the intestine, which mediates the regulation of ENS development by BMP2b in zebrafish. These results highlight a central role of the BMP-GDNF cascade in intestinal patterning and ENS development. Our results further demonstrate the key role of BMP2 in the etiology of HSCR in vitro and in vivo.

Real-time investigation of CAP transceivers with hybrid digital equalization for visible light communication.

In a practical light emitted diodes (LEDs)-based visible light communication (VLC) system, high-speed transmission is generally limited by the LED bandwidth. To address the bandwidth limitation, a hybrid digital linear and decision-feedback equalization (DFE) is investigated to improve the transmission performance (or spectral efficiency) in the carrier-less amplitude phase modulation (CAP)-based VLC systems. A real-time CAP-VLC transceiver with the hybrid digital equalization is designed, based on which 200 Mb/s transmission is successfully demonstrated over a 15 m VLC link with the commercial red LEDs (bandwidth: 6.5 MHz). In the real-time CAP-VLC system, the baseline wander (BLW) is observed, due to the removal of the low-frequency components with a direct current (DC) block. The BLW effect can be mitigated by increasing the roll-off factor. However, this roll-off factor affects the equalization performance, due to an increased loss in the signal spectrum beyond the system bandwidth. Optimization of the roll-off factor and filter length is required. Experimental results show that, with the optimized real-time transceiver design, the hybrid Wiener/recursive least squares (RLS) and DFE significantly improves the error vector magnitude (EVM) performance compared with the DFE. In addition, the digital signal processing (DSP) complexity is discussed.

Behavioural disorders in children with pectus excavatum in China: a retrospective cohort study with propensity score matching and risk prediction model.

OBJECTIVES: Surgical repair of pectus excavatum is typically carried out immediately prior to puberty. However, at the time of surgery, some psychosocial issues, such as behavioural disorders may already have developed and the likelihood of these psychosocial disorders resolving after surgery is unclear. For this reason, some surgeons choose to perform surgical repair at an earlier age in some children. The study retrospectively compares the rate of behavioural disorders in children undergoing the Nuss procedure at 4 vs. 10 years of age. We also attempted to develop a model to predict the risk of behavioural disorders in 10 year-old patients. METHODS: The current study included children receiving Nuss procedure for pectus excavatum at either 4 or 10 years of age. The presence/absence of behavioural disorder was assessed preoperatively, and in the third year, after removal of the bar. A propensity score matching (PSM) analysis was conducted to reduce the potential for confounding by baseline factors. Multivariable logistic regression was conducted to establish a model to predict the risk of behavioural disorders in the third year after the removal of the bar. The model was accessed by discrimination and calibration. A formula and a nomogram were developed based on the results. RESULTS: The number of patients in each group was 45 after PSM. The rate of behavioural disorders at the baseline was significantly higher in the children undergoing Nuss procedure at 10 years of age [36% vs 20%, odds ratio (OR) 2.21, 95% confidence interval (CI) 0.85-5.72; P = 0.157]. The rate of behavioural disorders in the third year after the removal of the bar was 36% and 18% in children undergoing surgery at 10 and 4 years of age, respectively (OR 2.55, 95% CI 0.96-6.79; P = 0.094). The rate of persistent behavioural disorders, defined as continuing to have behavioural disorders in the third year after the removal of the bar in those with behavioural disorders at the baseline, was 88% vs 56% (OR 3.47, 95% CI 0.56-21.36; P = 0.204). Two patients (4%) relapsed in each group. A risk prediction model by variables of gender, Haller index, pulmonary function and score of Child Behaviour Checklist at the baseline was provided. CONCLUSIONS: The rate of behavioural disorders was considerably lower in children who underwent the Nuss procedure at 4 years of age than at 10 years of age. Behavioural disorders may not readily resolve after surgery. Performing surgery at an early age rather than just before puberty may be better for psychosocial development. Psychosocial aid is necessary in addition to surgery to address behavioural disorders.

Potential association of long noncoding RNA HA117 with tetralogy of Fallot.

Tetralogy of Fallot (TOF) is a congenital heart disease characterized by abnormal cardiomyocyte differentiation in the right ventricular outflow tract (RVOT), and HA117 is a novel long noncoding RNA (lncRNA) with anti-differentiation roles. To investigate the potential association of HA117 with TOF, we collected 84 RVOT tissues from patients with TOF. We determined the expression of HA117 in RVOT samples from TOF patients and collected clinical data to conduct a cross-sectional and short-term follow-up study. McGoon ratio, Nakata index, and left ventricular end-diastolic volume index (LVEDVI) were negatively correlated with the expression of HA117 based on subgroup analysis, correlation analysis and logistic regression analysis. Additionally, cardiopulmonary bypass (CPB) time and ICU stay were longer in patients with higher expression of HA117 than in patients with lower expression of HA117. Furthermore, percentage improvement in SPO2 was significantly reduced in patients with increased HA117 expression at 6 months after surgery. Our results suggested that the increased expression of the novel lncRNA HA117 is a risk factor for unfavorable McGoon ratio, Nakata index and LVEDVI in TOF patients. Additionally, an increased expression of HA117 might lead to adverse short-term outcomes in TOF patients.

Changes in resting pulmonary function testing over time after the Nuss procedure: A systematic review and meta-analysis.

BACKGROUND: Pectus excavatum, the most common congenital chest wall deformity in pediatric patients, leads to pulmonary dysfunction. There is no consensus regarding the effectiveness of the Nuss procedure for recovering pulmonary function. In this meta- analysis, we focused on the changes that occur in pulmonary function after the Nuss procedure. METHODS: We performed a literature search in the MEDLINE, Embase, Cochrane library and PubMed databases. The included studies were required to contain pulmonary function tests with results adjusted to predicted values both before and after the Nuss procedure. The key outcomes of interest in this analysis were pulmonary function measured as forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC). Subgroup analyses were performed based on time since surgery and the mean ages of the patients when they underwent surgery by forest plots and meta-regressions. RESULTS: Thirteen studies involving 465 participants were included in this review. The standard mean difference (SMD) observed in FEV1 and FVC after surgery were 0.17 (95% CI, 0.01-0.33, p=0.04) and -0.18 (95% CI, -0.41-0.06, p=0.14), respectively. The overall meta-regression SMD of FEV1 and FVC by time since surgery were 1.21 (95% CI, 1.04-1.41, p=0.020) and 1.38 (95% CI, 1.05-1.83, p=0.027), respectively. We found evidence of a temporal relationship between time at which pulmonary function tests were performed after surgery and predicted FEV1 and FVC values. The SMD of FEV1 (0.26, p=0.012) was slightly higher in group evaluated more than 2year after initial surgery. CONCLUSIONS: Abnormal resting pulmonary functions tests performed prior to surgery showed an initial depression after surgery. The FEV1 of patients slightly increased at 2year post surgery compared with the baseline. Further studies with longer term follow-up are still needed to determine if pulmonary function could improve to normal after surgery. LEVELS OF EVIDENCE: Level of evidence: 4 (based on lowest level of article analyzed in meta-analysis/systematic review).

BMP4 knockdown of NCSCs leads to aganglionosis in the middle embryonic stage.

Transplacental bone morphogenetic protein (BMP)4 RNA interference (RNAi) is a technique used to knockdown genes in embryos. BMP4 are essential for the development of nervous system in the differentiation of neural crest stem cells (NCSCs). The failure of differentiation and migration of NCSCs may lead to aganglionosis. In the present study, pregnant mice were divided into three groups: Ringer's group, pSES group and RNAi­BMP4 group. In order to silence the BMP4 gene in the first generation (F1), 11.5 day pregnant mice were injected with the small interfering RNA BMP4 plasmid, pSES or Ringer's solution via the tail vein. Semi­quantitative reverse transcriptase­polymerase chain reaction (RT­PCR)and western blotting were employed to ensure the downregulation of BMP4. Finally, X­rays were performed following a barium enema. Aganglionosis was diagnosed by general anatomy and immunohistochemistry. Compared with the control group, transplacental RNAi was able to downregulate the BMP4­Smad4 of 11.5 day embryos, as determined by semi­quantitative RT­PCR and western blotting. The megacolons of the mice were demonstrated by X­ray and confirmed by general anatomy. Aganglionosis of colonic mucosa and submucosa were diagnosed by pathology, and immunohistochemistry. Knockdown of BMP4 in pregnant mice at the middle embryonic stage led to aganglionosis. It was therefore demonstrated that BMP­Smad was essential to the NCSCs of middle stage embryos. BMP­Smad served important roles in the generation of aganglionosis. This technique of knockdown BMP4 gene may be used to establish an aganglionosis mouse model.

Artesunate inhibits proliferation and invasion of mouse hemangioendothelioma cells in vitro and of tumor growth in vivo.

Artesunate has been demonstrated to be a novel potential antitumor agent in numerous studies. However, its efficacy in infantile hemangioma is unknown. The aim of the present study was to investigate the role of artesunate in the control of vascular tumor biological behavior and molecular mechanism using mouse hemangioendothelioma endothelial (EOMA) cells and a nude mouse model. Cell viability, apoptosis and invasion were determined by an MTT assay, flow cytometric analysis and Transwell invasion assay, respectively. Reverse transcription-quantitative polymerase chain reaction and western blotting were utilized to examine the expression of genes and proteins. Inoculated EOMA cells were injected into the subcutaneous tissues of nude mice to observe the effect of artesunate therapy on the vascular tumor, an effect that was similar to that of pingyangmycin (PYM). It was identified that artesunate treatment (0-600 µg/ml) inhibited cell growth in a time- and dose-dependent manner. Artesunate at 300 µg/ml significantly reduced the proliferation and invasion of EOMA cells, and significantly decreased the expression of vascular endothelial growth factor (VEGF)-A, VEGFR-1, VEGFR-2 and hypoxia inducible factor-1α over time; caspase-3 was simultaneously upregulated in vitro. Artesunate significantly inhibited tumor growth, and the curative effect was similar to that observed with PYM in vivo. It was concluded that artesunate could effectively inhibit the growth of vascular tumors, and thus could be a novel drug candidate for the treatment of infantile hemangioma.

All-optical mode-group multiplexed transmission over a graded-index ring-core fiber with single radial mode.

We present a design of graded-index ring-core fiber (GI-RCF) supporting 3 linearly polarized (LP) mode-groups (i.e. LP01, LP11 and LP21) with a single radial index of one for mode-division multiplexed (MDM) transmission. Reconfigurable spatial light modulator (SLM) based spatial (mode) (de)multiplexers are used to systematically characterize spatial/temporal modal properties of the GI-RCF. We also demonstrate all-optical mode-group multiplexed transmissions over a 360m fabricated GI-RCF without using multiple-input multiple-output digital signal processing (MIMO DSP).

HA117 endows HL60 cells with a stem-like signature by inhibiting the degradation of DNMT1 via its ability to down-regulate expression of the GGL domain of RGS6.

All-trans retinoic acid (ATRA) induces complete remission in almost all patients with acute promyelocytic leukemia (APL) via its ability to induce the in vivo differentiation of APL blasts. However, prolonged ATRA treatment can result in drug resistance. In previous studies, we generated a multi-drug-resistant HL60/ATRA cell line and found it to contain a new drug resistance-related gene segment, HA117. In this study, we demonstrate that ATRA induces multi-drug-resistant subpopulations of HL60 cells with a putative stem-like signature by up-regulating the expression of the new gene segment HA117. Western blot analysis and quantitative real-time PCR demonstrated that HA117 causes alternative splicing of regulator of G-protein signaling 6 (RGS6) and down-regulation of the expression of the GGL domain of RGS6, which plays an important role in DNA methyltransferase 1 (DNMT1) degradation. Moreover, DNMT1 expression was increased in multi-drug resistance HL60/ATRA cells. Knockdown of HA117 restored expression of the GGL domain and blocked DNMT1 expression. Moreover, resistant cells displayed a putative stem-like signature with increased expression of cancer steam cell markers CD133 and CD123. The stem cell marker, Nanog, was significantly up-regulated. In conclusion, our study shows that HA117 potentially promotes the stem-like signature of the HL60/ATRA cell line by inhibiting by the ubiquitination and degradation of DNMT1 and by down-regulating the expression of the GGL domain of RGS6. These results throw light on the cellular events associated with the ATRA-induced multi-drug resistance phenotype in acute leukemia.

miRNA Profiling Reveals Dysregulation of RET and RET-Regulating Pathways in Hirschsprung's Disease.

Hirschsprung's disease (HSCR), the most common congenital malformation of the gut, is regulated by multiple signal transduction pathways. Several components of these pathways are important targets for microRNAs (miRNAs). Multiple miRNAs have been associated with the pathophysiology of HSCR, and serum miRNAs profiles of HSCR patients have been reported, but miRNA expression in HSCR colon tissue is almost completely unexplored. Using microarray technology, we screened colon tissue to detect miRNAs whose expression profiles were altered in HSCR and identify targets of differentially expressed miRNAs. Following filtering of low-intensity signals, data normalization, and volcano plot filtering, we identified 168 differentially expressed miRNAs (104 up-regulated and 64 down-regulated). Fifty of these mRNAs represent major targets of dysegulated miRNAs and may thus important roles in the pathophysiology of HSCR. Pathway analysis revealed that 7 of the miRNA targets encode proteins involved in regulation of cell proliferation and migration via RET and related signaling pathways (MAPK and PI3K/AKT). Our results identify miRNAs that play key roles in the pathophysiology of the complex multi-factorial disease HSCR.

Evaluation of postoperative anal functions using endoanal ultrasonography and anorectal manometry in children with congenital anorectal malformations.

PURPOSE: The aim of this study was to assess the postoperative anorectal anatomy and function in children with congenital anorectal malformations (ARM) using endoanal ultrasonography (EUS) and anorectal manometry. METHODS: This study included 47 children who had undergone posterior sagittal anorectoplasty (PSARP) or transperineal anorectoplasty for the repair of an ARM. Children were grouped according to symptoms of defecation disorder, including normal defecation, fecal soiling, fecal incontinence, and constipation. Ten children with no history of anal or rectal diseases served as healthy controls. A well-established scoring system was used for the evaluation of anal function and defecation disorder. RESULTS: EUS showed significant differences in the thickness of the interior sphincter between the ARM patients and the healthy controls (P<0.05). However, no significant difference was found in the thickness of the interior sphincters between the PSARP group and transperineal anorectoplasty group (P>0.05). Anorectal manometry showed that the balloon volumes were significantly different between the surgical group and the control group (P<0.01), and between the low defect group and the intermediate-high defect group (P=0.022). Balloon volume was significantly correlated with anal function scores (r=-0.30, P<0.05). CONCLUSIONS: EUS and anorectal manometry can provide objective assessment of postoperative anorectal anatomy and function in children with ARM.

Detection and preliminary screening of the human gene expression profile for Hirschsprung's disease.

The present study investigated a genome microarray of colorectal lesions (spasm segments) in children with Hirschsprung's disease (HSCR), and analyzed the results. In addition, the present study screened for differentially expressed genes in children with HSCR. Microarray technology was used to examine the human gene expression profiles of the colorectal lesions (spasm segments) of six children with HSCR, and three normal colon tissue samples. The data were analyzed be determining P­values of significance and absolute fold changes. Preliminary screening was performed to identify genes exhibiting significant differential expression in children with HSCR, and these target genes were analyzed in subsequent verification and analytical investigations. Of >20,000 detected human genes, the preliminary screenings demonstrated that 3,850 genes were differentially expressed and upregulated, with P<0.05 and >2­fold absolute changes in expression. In addition, 645 differentially expressed genes with P<0.05 and >2­fold absolute changes were downregulated. Of the upregulated genes, 118 were involved in classic signaling pathways, compared with 11 of the downregulated genes (P<0.001; absolute fold change >2­fold). HSCR etiology is complex and often involves multiple gene changes. Microarray technology can produce large quantities of gene expression data simultaneously, and analyzing this data using various techniques may provide a fast and efficient method for identifying novel gene targets and for investigating the mechanisms underlying HSCR pathogenesis.

Differential expression of FOXA1, DUSP6, and HA117 in colon segments of Hirschsprung's disease.

OBJECTIVE: To describe the expression profiles of FOXA1, DUSP6, and HA117 in different portions of the colon of patients diagnosed with Hirschsprung's disease (HSCR). METHODS: Colon specimens were collected from 34 HSCR patients and grouped into 3 segments: proximal anastomosis, dilated segment and stenotic segment. Levels of FOXA1, DUSP6, and HA117 RNA were evaluated by real-time PCR. Levels of FOXA1 and DUSP6 protein were analyzed by immunohistochemistry and Western blotting. RESULTS: The levels of FOXA1 and DUSP6 RNA were significantly lower in the stenotic segment compared to proximal anastomosis (P < 0.05). The level of HA117 RNA was significantly higher in the stenotic segment compared to proximal anastomosis (P < 0.05). In proximal anastomosis, FOXA1 and DUSP6 were both expressed at the protein level in ganglion cells and nerve fibers between the circular and longitudinal muscles. In the stenotic segments, positive staining for FOXA1 and DUSP6 was diminished. The levels of FOXA1 and DUSP6 protein were significantly lower in the stenotic segment compared to proximal anastomosis (P < 0.05). CONCLUSION: Suppression of the FOXA1/DUSP6 signaling pathway may contribute to the development of HSCR. LncRNA HA117 may have an anti-differentiation function, and play a pivotal role in the progression of HSCR.

Expression profiles of HA117 and its neighboring gene DPF3 in different colon segments of Hirschsprung's disease.

Hirschsprung's disease (HSCR) is characterized by the absence of enteric ganglion cells along variable regions of the colon. Established theory demonstrates that HSCR is the consequence caused by the abnormal arrest of the migration and differentiation of neural crest-derived stem cells (NCSCs). And retinoid signaling was considered to be involved. We speculated that, HA117, a retinoid-related transcript of a long noncoding RNA (LncRNA), may be involved in the genesis of HSCR. In current research, colon specimens were collected from 25 HSCR patients and grouped into 3 segments: proximal anastomosis, dilated segment and stenotic segment. Real-Time PCR was used to analyze the expression profiles of HA117 and its neighboring gene DPF3 in different colon segments. Fluorescence in situ hybridization (FISH) was employed to detect the distribution of HA117 in the gut wall. Immunohistochemistry was performed to analyze the protein expression of DPF3 in different colon segments. HA117 expression in stenotic segment was higher compared to proximal anastomosis and dilated segment (p < 0.05). Whereas DPF3b mRNA was lower in stenotic segment than that in two other segments (p < 0.05). FISH detected HA117 was distributed in mucosa and muscle layer, mainly present in stenotic segment. Immunohistochemical staining showed that intensive DPF3 staining occurred in proximal anastomosis and the positive staining was hardly observed in stenotic segment. The results suggested that HA117 may be a factor exerting an anti-differentiation or or anti-maturation role in the genesis of HSCR. This gave us a novel cue for better understanding the etiology of HSCR.

Thirty-five consecutive pediatric living donor liver transplantation: experiences and lessons learned from a single center.

BACKGROUND/AIMS: In the last 10 years, the early patient outcome of liver transplantation in children have significantly improved. Now the overall outcomes of pediatric LT are promising. METHODOLOGY: In this study, we review the outcome of all pediatric liver transplants performed at our center and analyze our experiences with pediatric liver transplant. Of the 34 liver transplant recipients, 26 were highly urgent (19.7%). RESULTS: Actuarial patient survival rates at 6, 12, and 36 months was 82.9%, 79.8% and 72.2%, respectively. Indications for liver transplant were biliary atresia (n = 22), Wilson's disease (n = 4), glycogen storage disease (n = 3), portal vein cavernous transformation (PVCT) (n = 3), fulminant liver failure (n = 1), and cryptogenic cirrhosis (n = 1). The main complications were surgical complications (including biliary complications, portal vein or arterial complications, intestinal perforation, postoperative bleeding, of which 20% required reoperation) and infections. Cyclosporine was the primary immunosuppressive agent used in 70.6% of patients, with a 26.5% incidence of acute allograft rejection within the first six months. One children underwent re-transplant as a result of hepatic artery thrombosis. Nine children died during followup. They were related to portal vein thrombosis (one), chronic rejection (one), sepsis (one), post-transplant lymphoproliferative disease (one) and so on. CONCLUSIONS: The overall outcomes of pediatric liver transplantation at our center are promising. Advances in post-transplant care and monitoring of the recipients, technical refinements enable these results.

Colorectal polyp model established by transplacental BMP4 RNAi.

Previous studies have shown that disruption of the bone morphogenetic protein (BMP) signaling pathway is an important cause of intestinal cancer in human and animal models. Thus, the purpose of this study was to construct a Balb/C model of colorectal polyps. Pregnant mice at 9.5 days gestation were injected via the tail vein with the pSES-Si BMP4 plasmid bearing a fluorochrome (DsRed) reporter, in order to silence the BMP4 gene in the first generation (F1); this group of mice was named the pSES-BMP4 group Intestinal fluorescence was detected at 1-, 4- and 8-week­old F1 mice, and reverse transcription-polymerase chain reaction (RT-PCR) and western-blotting assays were used to determine changes in the expression of BMP4. A dissecting microscope and hematoxylin and eosin (H&E) staining were used to observe the cell morphology and appearance of the polyps. DsRed fluorescence was observed in the intestines of 1-week-old F1 mice of the pSES-BMP4 group. BMP4 expression at the mRNA and protein level was reduced in 1-, 4- and 8-week-old F1 mice (P<0.05). However, the level of Smad4 mRNA was only reduced in 8-week-old F1 mice (P<0.05). Multiple hyperplasic polyps emerged in the colon and rectum of the intestines of 4-week-old F1 mice in the pSES-BMP4 group. The size of colorectal polyps increased at 8 weeks, when vessels and polyp pedicles became apparent. In conclusion, silencing of the BMP4 gene using transplacental RNAi injection can induce formation of colorectal polyps in mice.

Vandetanib-induced inhibition of neuroblastoma cell migration and invasion is associated with downregulation of the SDF-1/CXCR4 axis and matrix metalloproteinase 14.

Rearranged during transfection (RET) is widely expressed in neuroblastoma (NB) and partly contributes to high metastatic potential and survival of NB. The aim of the present study was to investigate whether vandetanib (a RET inhibitor) inhibits proliferation, migration and invasion of NB cells in vitro. The effects of vandetanib on the proliferation, apoptosis and cell cycle and on RET phosphorylation of SK-N-SH and SH-SY5Y cells were evaluated in vitro. The migration and invasion potential of vandetanib-treated NB cells were analyzed using Transwell cell migration and invasion assays, respectively. qPCR, western blotting and immunofluorescence were used to detect mRNA and protein levels in NB cells treated with vandetanib. Our data demonstrated that vandetanib inhibits the proliferation of SK-N-SH and SH-SY5Y cells and that this inhibition is mediated by the induction of G1 phase cell cycle arrest at lower concentrations and by apoptosis at higher concentrations. In the presence of vandetanib, the migration and invasion of two NB cell lines were markedly decreased compared with the control group (p<0.01). In addition, our data showed that the levels of C-X-C chemokine receptor type 4 (CXCR4) and matrix metalloproteinase 14 (MMP14) mRNA expression in NB cell lines treated with vandetanib were significantly lower than those in the cells that were treated with vehicle (p<0.01) and similar results were obtained for protein levels as determined by western blotting and immunofluorescence analysis. Vandetanib may inhibit the proliferation, migration and invasion of NB cells in vitro. The potential mechanisms for the inhibition of NB migration and invasion by vandetanib may partly be attributed to the ability of vandetanib to suppress the expression of CXCR4 and MMP14 in human NB cells.