Vascular anomalies of the limb and trunk in children: a retrospective comparative study of endoscopic surgery and open surgery.

BACKGROUND: Endoscopic resection has been reported for vascular anomalies (VA) previously. However, there is no study comparing endoscopic resection surgery (ERS) with open resection surgery (ORS) in children. We aimed to compare clinical and cosmetic outcomes between two approaches in pediatric VA. METHODS: Between June 2018 and June 2023, 138 pediatric VA patients undergoing ERS or ORS were retrospectively reviewed. Propensity score matching (PSM) was performed to minimize selection bias. The Scar Cosmesis Assessment and Rating (SCAR) Scale and numerical rating scale (NRS) based on patient satisfaction were used for cosmetic assessment. RESULTS: After PSM for age, depth of lesion, size of lesion, and site of surgery, 72 patients (ERS = 24, ORS = 48) were analyzed. Patients undergoing ERS had longer operative time (164.25 ± 18.46 vs. 112.85 ± 14.26 min; P < 0.001), less estimated blood loss (5.42 ± 2.15 vs. 18.04 ± 1.62 ml; P < 0.001), and shorter median hospital stay (4.50 [3.00-5.00] vs. 6.00 [5.00-6.00] days; P < 0.001). The follow-up time was 8.04 ± 1.23 month for ERS group and 8.56 ± 1.57 month for ORS group. For aesthetic results, the median overall SCAR score in ERS was lower than that in ORS (2 [1-3] vs. 5 [4-5]; P < 0.001), and the subscales of "scar spread," "dyspigmentation," "track marks or suture marks," and "overall impression" were better. The median NRS score was higher (8 [7-8] vs. 6 [5-6]; P < 0.001) and length of scars was shorter (2.18 ± 0.30 vs. 8.75 ± 1.98 cm; P < 0.001) in ERS group than those in ORS group. The incidences of total complications and recurrence showed no significant difference between two groups. CONCLUSIONS: Endoscopic surgery can be a safe and effective option for pediatric VA in the limbs and trunk. It offers the advantages of improving aesthetic outcomes and reducing postoperative wound healing time.

Robot-assisted anorectal pull-through for anorectal malformations with rectourethral and rectovesical fistula: feasibility and short-term outcome.

BACKGROUND: Multiple structures in the anorectal area are closely related to defecation, voiding and sexual function. Although laparoscopic-assisted anorectal pull-through is widely accepted as a minimally invasive surgical technique, controversy still exists for ARMs with rectourethral fistulas. Intraoperative injuries more or less involve the perirectal sphincters and neurovascular tissue. METHODS: Seventeen selected infants with ARMs underwent robot-assisted anorectal pull-through (RAARP) between October 2016 and January 2018. The application of nerve- and sphincter-sparing technique in RAARP was detailed. The feasibility and early outcomes were evaluated. RESULTS: All procedures were completed without conversion. The robotic system facilitated clear dissections between different anatomical layers. Under direct vision, the fistula was easier to repair, and the rectal pouch was precisely placed in the center of the striated muscle complex. During the follow-up of 11.6 months, 13 patients resumed normal defecation. The other four children experienced mild constipation or fecal incontinence. Their continence and defecation functions showed favorable evolution. CONCLUSION: RAARP is a safe and effective alternative for the treatment of ARMs, which provides an advantage in further minimizing the injury to perirectal nerves and sphincters.

Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 cooperates with enhancer of zeste homolog 2 to promote hepatocellular carcinoma development by modulating the microRNA-22/Snail family transcriptional repressor 1 axis.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is an oncogenic long noncoding RNA that has been found to promote carcinogenesis and metastasis in many tumors. However, the underlying role of MALAT1 in the progression and metastasis of hepatocellular carcinoma (HCC) remains unclear. In this study, aberrantly elevated levels of MALAT1 were detected in both HCC specimens and cell lines. We found that knockdown of MALAT1 caused retardation in proliferation, migration, and invasion both in vivo and in vitro. Mechanistic investigations showed that Snail family transcriptional repressor 1 (SNAI1) is a direct target of microRNA (miR)-22 and that MALAT1 modulates SNAI1 expression by acting as a competing endogenous RNA for miR-22. Inhibition of miR-22 restored SNAI1 expression suppressed by MALAT1 knockdown. Furthermore, MALAT1 facilitated the enrichment of enhancer of zeste homolog 2 (EZH2) at the promoter region of miR-22 and E-cadherin, which was repressed by MALAT1 knockdown. Cooperating with EZH2, MALAT1 positively regulated SNAI1 by repressing miR-22 and inhibiting E-cadherin expression, playing a vital role in epithelial to mesenchymal transition. In conclusion, our results reveal a mechanism by which MALAT1 promotes HCC progression and provides a potential target for HCC therapy.

miRNA-558 promotes tumorigenesis and aggressiveness of neuroblastoma cells through activating the transcription of heparanase.

Heparanase (HPSE) is the endogenous endoglycosidase that degrades heparan sulfate proteoglycans and promotes the tumor growth, invasion, metastasis and angiogenesis. Our previous studies have shown that HPSE is highly expressed in neuroblastoma (NB), the most common extracranial solid tumor in childhood. However, the underlying regulatory mechanisms remain largely unknown. In this study, we identified one binding site of microRNA-558 (miR-558) within the HPSE promoter. In NB tissues and cell lines, miR-558 was up-regulated and positively correlated with HPSE expression. Gain- and loss-of-function studies demonstrated that miR-558 facilitated the transcript and protein levels of HPSE and its downstream gene, vascular endothelial growth factor, in NB cell lines. In addition, miR-558 enhanced the promoter activities of HPSE, and these effects were abolished by the mutation of the miR-558-binding site. Mechanistically, miR-558 induced the enrichment of the active epigenetic marker and RNA polymerase II on the HPSE promoter in NB cells in an Argonaute 1-dependent manner, which was abolished by repressing the miR-558-promoter interaction. Knockdown of endogenous miR-558 decreased the growth, invasion, metastasis and angiogenesis of NB cells in vitro and in vivo. In contrast, over-expression of miR-558 promoted the growth, invasion, metastasis and angiogenesis of SH-SY5Y and SK-N-SH cells. Restoration of HPSE expression prevented the NB cells from changes in these biological features induced by knockdown or over-expression of miR-558. These data indicate that miR-558 induces the transcriptional activation of HPSE via the binding site within promoter, thus facilitating the tumorigenesis and aggressiveness of NB.

miRNA-584-5p exerts tumor suppressive functions in human neuroblastoma through repressing transcription of matrix metalloproteinase 14.

Matrix metalloproteinase 14 (MMP-14) is a membrane-anchored MMP crucial for tumorigenesis and aggressiveness, and is highly expressed in neuroblastoma (NB), the most common extracranial solid tumor in childhood. Recent evidence shows the emerging roles of endogenous promoter-targeting microRNAs (miRNAs) in regulating gene transcription. However, the roles of miRNAs in the transcription of MMP-14 still remain largely unknown. In this study, through mining computational algorithm program and Argonaute-chromosome interaction dataset, we identified one binding site of miRNA-584-5p (miR-584-5p) within the MMP-14 promoter. In NB tissues, miR-584-5p was under-expressed and inversely correlated with MMP-14 expression, and was an independent prognostic factor for favorable outcome of patients. miR-584-5p precursor attenuated the expression of MMP-14 in a Dicer-dependent manner, resulting in decreased levels of vascular endothelial growth factor, in cultured NB cell lines. In addition, miR-584-5p suppressed the promoter activity of MMP-14, and mutation of miR-584-5p binding site abolished these effects. Mechanistically, miR-584-5p recruited Argonaute 2 to facilitate the enrichment of enhancer of zeste homolog 2, histone H3 lysine 27 trimethylation, and histone H3 lysine 9 dimethylation on MMP-14 promoter in NB cells, which was abolished by repressing the miR-584-5p-promoter interaction. Gain- and loss-of-function studies demonstrated that miR-584-5p suppressed the growth, invasion, metastasis, and angiogenesis of NB cells in vitro and in vivo. Moreover, restoration of MMP-14 expression rescued the NB cells from changes in these biological features. Taken together, these results indicate that promoter-targeting miR-584-5p exerts tumor suppressive functions in NB through repressing the transcription of MMP-14.

Intelectin 1 suppresses the growth, invasion and metastasis of neuroblastoma cells through up-regulation of N-myc downstream regulated gene 2.

BACKGROUND: Recent studies have revealed the potential roles of intelectin 1 (ITLN1) in tumorigenesis. However, its functions and underlying mechanisms in neuroblastoma (NB), the most common extracranial solid tumor in childhood, still remain largely unknown. METHODS: Human neuroblastoma cell lines were treated with recombinant ITLN1 protein or stably transfected with ITLN1 expression and short hairpin RNA vectors. Gene expression and signaling pathway were detected by western blot and real-time quantitative RT-PCR. Gene promoter activity and transcription factor binding were detected by luciferase reporter and chromatin immunoprecipitation assays. Growth and aggressiveness of tumor cells were measured by MTT colorimetry, colony formation, scratch assay, matrigel invasion assay, and nude mice model. RESULTS: Mining of public microarray databases revealed that N-myc downstream regulated gene 2 (NDRG2) was significantly correlated with ITLN1 in NB. Gain- and loss-of-function studies indicated that secretory ITLN1 facilitated the NDRG2 expression, resulting in down-regulation of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9), in NB cell lines SH-SY5Y, SK-N-BE(2), and SK-N-SH. Krüppel-like factor 4 (KLF4), a transcription factor crucial for NDRG2 expression, was up-regulated by ITLN1 in NB cells via inactivation of phosphoinositide 3-kinase (PI3K)/AKT signaling. Ectopic expression of ITLN1 suppressed the growth, invasion and metastasis of NB cells in vitro and in vivo. Conversely, knockdown of ITLN1 promoted the growth, invasion, and metastasis of NB cells. In addition, rescue experiments in ITLN1 over-expressed or silenced NB cells showed that restoration of NDRG2 expression prevented the tumor cells from ITLN1-mediated changes in these biological features. In clinical NB tissues, ITLN1 was down-regulated and positively correlated with NDRG2 expression. Patients with high ITLN1 or NDRG2 expression had greater survival probability. CONCLUSIONS: These findings indicate that ITLN1 functions as a tumor suppressor that affects the growth, invasion and metastasis of NB through up-regulation of NDRG2.

Association of Ureaplasma urealyticum colonization with development of bronchopulmonary dysplasia: a systemic review and meta-analysis.

There is controversy regarding the roles of Ureaplasma urealyticum (U. urealyticum) colonization in the development of bronchopulmonary dysplasia (BPD). This study explored the association between U. urealyticum and bronchopulmonary dysplasia at 36 weeks post-menstrual age (BPD36). Studies published before December 31, 2013 were searched from Medline, Embase, Ovid, Web of Science, and Cochrane databases, with the terms "Ureaplasma urealyticum", "chronic lung disease", or "BPD36" used, and English language as a limit. The association between U. urealyticum colonization and BPD36 was analyzed with RevMan 4.2.10 software, using the odds ratio (OR) and relative risk (RR) for dichotomous variables. Out of the enrolled 81 studies, 11 investigated the BPD36 in total 1193 infants. Pooled studies showed no association between U. urealyticum colonization and subsequent development of BPD36, with the OR and RR being 1.03 (95% CI=0.78-1.37; P=0.84) and 1.01 (95% CI= 0.88-1.16, P=0.84), respectively. These findings indicated no association between U. urealyticum colonization and the development of BPD36.

Over-expression of testis-specific expressed gene 1 attenuates the proliferation and induces apoptosis of GC-1spg cells.

The effects of over-expression of testis-specific expressed gene 1 (TSEG-1) on the viability and apoptosis of cultured spermatogonial GC-1spg cells were investigated, and the immortal spermatogonial cell line GC-1spg (CRL-2053™) was obtained as the cell model in order to explore the function of TSEG-1. We transfected the eukaryotic vector of TSEG-1, named as pEGFP-TSEG-1 into cultured spermatogonial GC-1spg cells. Over-expression of TSEG-1 inhibited the proliferation of GC-1spg cells, and arrested cell cycle slightly at G0/G1 phase. Transfection of TSEG-1 attenuated the transcript levels of Ki-67, PCNA and cyclin D1. In addition, over-expression of TSEG-1 induced early and late apoptosis, and reduced the mitochondrial membrane potential of GC-1spg cells. Moreover, transfection of TSEG-1 significantly enhanced the ratio of Bax/Bcl-2 and transcript levels of caspase 9, and decreased the expression of Fas and caspase 8 in GC-1spg cells. These results indicated over-expression of TSEG-1 suppresses the proliferation and induces the apoptosis of GC-1spg cells, which establishes a basis for further study on the function of TSEG-1.

Current trends and prospects of surgical techniques for hepatoblastoma.

Hepatoblastoma, a common extracranial malignant solid tumor in childhood, is often detected at an advanced stage and is difficult to treat surgically. Despite the availability of multiple comprehensive treatments that can be combined with surgery, hepatoblastoma treatment outcomes remain poor. Surgery is the main treatment strategy for hepatoblastoma, but it faces many challenges, including tumor attachment to surrounding tissues, tumor wrapping or invading of vital organs and tissues, the presence of giant or multiple tumors, distant metastasis, the formation of a tumor thrombus, and significant surgical trauma. In this review, we discuss recent research advances and propose potential strategies for overcoming these challenges. Such strategies may improve the rate of hepatoblastoma resection and local control in children, as well as reduce complications and trauma.

Preparation and characterization of fennel (Foeniculum vulgare miller) essential oil/hydroxypropyl-ß-cyclodextrin inclusion complex and its application for chilled pork preservation.

Fennel essential oil (FEO) a natural spice that has versatile biological activities. However, the direct use of FEO is limited due to its water insolubility and poor stability. Chilled pork is prone to spoilage during storage. To solve these problems, this study aimed to prepare an inclusion complex (IC) of FEO with hydroxypropyl-ß-cyclodextrin via co-precipitation and apply it to the preservation of chilled pork. Results indicated that the optimal parameters were encapsulating temperature 37 °C, wall-core ratio 14:1 g/mL, stirring speed 600 r/min, and encapsulating time 240 min, obtaining an encapsulation efficiency of 83.75%. The results of scanning electron microscopy, Fourier transform infra-red spectroscopy, and nuclear magnetic resonance demonstrated the successful preparation of IC. The release of FEO from IC was controllable through adjusting the different temperatures and relative humidities. Furthermore, IC effectively delayed the spoilage of chilled pork and extended its shelf life by 6 days at 4 °C.

Methyl jasmonate abolishes the migration, invasion and angiogenesis of gastric cancer cells through down-regulation of matrix metalloproteinase 14.

BACKGROUND: Recent evidence indicates that methyl jasmonate (MJ), a plant stress hormone, exhibits anti-cancer activity on human cancer cells. The aim of this study is to determine whether sub-cytotoxic MJ can abolish the migration, invasion and angiogenesis gastric cancer cells. METHODS: Human gastric cancer cell lines SGC-7901 and MKN-45 were treated with diverse concentrations of MJ. Cell viability, proliferation, migration, invasion and angiogenesis capabilities of cancer cells were measured by MTT colorimetry, EdU incorporation, scratch assay, matrigel invasion assay, and tube formation assay. Gene expression was detected by western blot and real-time quantitative RT-PCR. Binding of transcription factor on gene promoter was detected by chromatin immunoprecipitation. RESULTS: Sub-cytotoxic (0.05 to 0.2 mM) MJ attenuated the migration, invasion and angiogenesis, but not the cell viability or proliferation, of gastric cancer cells in a time- and dose-dependent manner, with down-regulation of matrix metalloproteinase 14 (MMP-14) and its downstream gene vascular endothelial growth factor. Restoration of MMP-14 expression rescued the SGC-7901 and MKN-45 cells from sub-cytotoxic MJ-inhibited migration, invasion and angiogenesis. In addition, sub-cytotoxic MJ decreased the specificity protein 1 (Sp1) expression and binding on MMP-14 promoter, while restoration of Sp1 expression rescued the cancer cells from sub-cytotoxic MJ-mediated defects in MMP-14 expression, migration, invasion and angiogenesis. CONCLUSIONS: Sub-cytotoxic MJ attenuates the MMP-14 expression via decreasing the Sp1 expression and binding on MMP-14 promoter, thus inhibiting the migration, invasion and angiogenesis of gastric cancer cells.

Robotic resection of paediatric solid tumours at a single institution.

BACKGROUND: To explore the clinical application of robotic-assisted surgery in paediatric solid tumours and to explore its feasibility. METHODS: From 2015 to 2022, 53 children with solid tumours underwent robotic-assisted surgery in our centre were retrospectively analysed. RESULTS: The mean weight of the patients was 27.7 kg, and the mean age was 6.7 years. The average tumour volume was 5.5*4.6*3.7 cm. Two procedures (3.8%) were converted. The mean total operative time was 198.5 min. The mean estimated blood loss was 27.1 ml, and no intraoperative complications occurred. Two (3.8%) patients had postoperative complications. At a median follow-up of 21.2 months, one (1.9%) patient with malignant tumours stopped treatment, and two (3.8%) patients developed tumour recurrence. CONCLUSIONS: Robotic-assisted tumour resection is feasible in highly selected cases of young age, light weight, huge tumour or malignant tumour.

TSEG-1, a novel member of histone H2A variants, participates in spermatogenesis via promoting apoptosis of spermatogenic cells.

A novel variant of histone H2A, named as testis specific expressed gene 1 (TSEG-1, approved symbol: H2afb1), was identified from adult mouse testis. The TSEG-1 gene is 610-bp in length and consists of one exon. TSEG-1 transcript was robustly and exclusively expressed in adult mouse testis, mainly in spermatocytes. In developmental testis, the TSEG-1 transcript was robustly expressed since postnatal day (P) 21, peaked at P30, and gradually decreased in the testis of aging mouse. The surgical cryptorchidism mouse model showed an increase in the TSEG-1 expression, accompanied by enhanced apoptosis of spermatogenic cells. The EGFP-tagged TSEG-1 protein is located in the nuclei of cultured spermatocytes (GC-2spd cells). Transfection of TSEG-1 into GC-2spd cells resulted in suppressed cell viabilities, increased apoptosis, and decreased mitochondrial membrane potential. Intratesticular injection of TSEG-1 resulted in increased apoptosis of spermatogenic cells in vivo. These results suggest that TSEG-1 may participate in the spermatogenesis via regulating the apoptosis of spermatogenic cells.

Laparoscopic versus open orchiopexy for non-palpable undescended testes in children: a systemic review and meta-analysis.

BACKGROUND: Laparoscopic orchidopexy (LO) has been widespread used in the management of non-palpable testis (NPT) in children. However, the real advantages of LO over traditional open orchidopexy (OO) still remain exclusive. METHODS: Published studies until August 31, 2010 were searched from Medline, Embase, Ovid, Web of Science, and Cochrane databases. Randomized controlled trials (RCTs) and observational clinical studies (OCSs) with a comparison of LO and OO were included for a systemic review and meta-analysis. RESULTS: Out of 226 studies, 2 RCTs and 5 OCSs were eligible for inclusion criteria, comprising 176 cases of LO and 263 cases of OO. The hospital stay of LO was significantly shorter than that of OO (WMD = -0.66; 95% confidence interval [CI] = -0.95 to -0.37; P < 0.00001). However, no significant difference was observed between LO and OO in operative time (WMD = 4.02; 95% CI = -9.89 to 17.93; P = 0.57), time to resume feeding (WMD = -2.29; 95% CI = -6.78 to 2.20; P = 0.32) or full activity (WMD = -9.71; 95% CI = -27.84 to 8.42; P = 0.29), recurrence (OR = 0.60; 95% CI = 0.13 to 2.72; P = 0.51), viable testis rate (OR = 1.61; 95% CI = 0.30 to 8.52; P = 0.58), success rate (OR = 1.41; 95% CI = 0.44 to 4.46; P = 0.56), and testicular atrophy (OR = 1.70; 95% CI = 0.49 to 5.98; P = 0.40). CONCLUSION: Although shorter hospital stay is noted in LO, it does not provide significant advantage over open surgery for treating NPT. However, due to the publishing bias, a series of RCTs are necessary to explore the efficiencies of LO in the management of NPT in children.

Small RNA interference-mediated gene silencing of heparanase abolishes the invasion, metastasis and angiogenesis of gastric cancer cells.

BACKGROUND: Heparanase facilitates the invasion and metastasis of cancer cells, and is over-expressed in many kinds of malignancies. Our studies indicated that heparanase was frequently expressed in advanced gastric cancers. The aim of this study is to determine whether silencing of heparanase expression can abolish the malignant characteristics of gastric cancer cells. METHODS: Three heparanase-specific small interfering RNA (siRNAs) were designed, synthesized, and transfected into cultured gastric cancer cell line SGC-7901. Heparanase expression was measured by RT-PCR, real-time quantitative PCR and Western blot. Cell proliferation was detected by MTT colorimetry and colony formation assay. The in vitro invasion and metastasis of cancer cells were measured by cell adhesion assay, scratch assay and matrigel invasion assay. The angiogenesis capabilities of cancer cells were measured by tube formation of endothelial cells. RESULTS: Transfection of siRNA against 1496-1514 bp of encoding regions resulted in reduced expression of heparanase, which started at 24 hrs and lasted for 120 hrs post-transfection. The siRNA-mediated silencing of heparanase suppressed the cellular proliferation of SGC-7901 cells. In addition, the in vitro invasion and metastasis of cancer cells were attenuated after knock-down of heparanase. Moreover, transfection of heparanase-specific siRNA attenuated the in vitro angiogenesis of cancer cells in a dose-dependent manner. CONCLUSIONS: These results demonstrated that gene silencing of heparanase can efficiently abolish the proliferation, invasion, metastasis and angiogenesis of human gastric cancer cells in vitro, suggesting that heparanase-specific siRNA is of potential values as a novel therapeutic agent for human gastric cancer.

Abnormal expression of early growth response 1 in gastric cancer: association with tumor invasion, metastasis and heparanase transcription.

Given that previous studies indicated that early growth response 1 (EGR1) exerts pro-tumorigenic effects through regulating heparanase (HPA) transcription, it was hypothesized that EGR1 may correlate with the progression of gastric cancer. One hundred and fifteen patients with gastric cancer were evaluated for the protein and transcript expression of EGR1 and HPA on immunohistochemistry and real-time quantitative polymerase chain reaction (PCR). In normal gastric mucosa, EGR1 protein expression was absent or weak, whereas gastric cancer was positive for EGR1. Seventy gastric cancer patients (60.9%) were positive for cytoplasmic EGR1 expression, and 26 (22.6%) had nuclear expression of EGR1. In the gastric cancer examined, the transcripts of EGR1 were enhanced compared to that of normal gastric mucosa, and positively correlated with EGR1 protein expression. The cytoplasmic or nuclear expression of EGR1 and its transcripts in gastric cancer was positively correlated with tumor infiltration (P < 0.05), lymph node and distant metastasis (P < 0.05), tumor node metastasis (TNM) stages (P < 0.05), but not with age, gender, tumor location and size, histological types or differentiation. Moreover, the protein and transcript expression of EGR1 was correlated with that of HPA in gastric cancer. These results indicate that aberrant expression of EGR1 in gastric cancer is associated with tumor invasion and metastasis, and HPA transcription.

Runt-related transcription factor 1 promotes apoptosis and inhibits neuroblastoma progression in vitro and in vivo.

BACKGROUND: Runt-related transcription factor 1 (RUNX1) is a heterodimeric transcription factor that binds to the core element of many enhancers and promoters and can accelerate apoptosis in various tumors. However, the regulatory mechanisms underlying RUNX1 expression in neuroblastoma (NB), a highly malignant tumor in childhood, remain largely unclear. In this study, we aimed to assess the role of RUNX1 in NB and to reveal the underlying mechanisms that may contribute to finding a potential therapeutics strategy against NB. METHODS: Growth, invasion, metastasis and angiogenesis were assessed using Cell Counting Kit-8 (CCK-8) immunocytochemistry, and studies involving soft agar, cell invasion, tube formation and whole animals. The levels of expression were measured using real-time quantitative PCR for RNA, Western blot and immunostaining analyses for proteins. Luciferase reporter and chromatin immunoprecipitation assays indicated that RUNX1 directly binds within the BIRC5, CSF2RB and NFKBIA promoter regions to facilitate transcription. The level of apoptosis was assessed by determining mitochondrial membrane potential and flow cytometry. RESULTS: RUNX1 was highly expressed in ganglioneuroma (GN) and well-differentiated (WD) tissues relative to the poorly differentiated (PD) and undifferentiated (UD) ones. Moreover, RUNX1 effectively reduced cell viability, invasion, metastasis, angiogenesis, and promoted apoptosis in vitro and in vivo. RUNX1 reduced BIRC5 transcription and increased CSF2RB and NFKBIA transcription by directly binding BIRC5, CSF2RB and NFKBIA promoters. In addition, cytotoxic drugs, especially cisplatin, significantly increased RUNX1 expression in NB cells and promoted apoptosis. CONCLUSIONS: These data show that RUNX1 is an independent surrogate marker for the progression of NB and it can be used for monitoring NB prognosis during therapy.

Enhanced expression of resistin-like molecule beta in human colon cancer and its clinical significance.

Previous studies have indicated that resistin-like molecule beta (RELM beta), an intestinal goblet cell-specific protein, is markedly increased in the intestinal tumors of min mice and over-expressed in a human colon cancer cell line. We hypothesized that RELM beta might be enhanced in human colon cancer. The aim of this study was to examine the clinical importance of RELM beta expression in colon cancer patients and to correlate its expression with various clinicopathological parameters, upstream regulatory molecule expression, tumor proliferative capacity, and patients' survival. Of the 80 colon cancer patients studied, 65 (81.25%) tested positive for RELM beta, mainly in the cytoplasm of colon mucosa. Contrasting sharply with the strongly RELM beta-positive tumors, normal colon mucous membrane was negative or weakly positive. RELM beta positivity in colon cancer was correlated with histological grade of differentiation and lymph node metastasis, but not with age, gender, tumor location and size, tumor infiltration, Dukes' stage, liver metastasis, and venous invasion. RELM beta expression was significantly correlated with the expression of transcription factor CDX-2 (P < 0.01) but not with that of proliferative index Ki-67 (P > 0.05). The mean postoperative survival time (2.76 years) of RELM beta-positive patients was significantly longer than that (1.26 years) of RELM beta-negative patients (P = 0.032). These findings support evidence of the enhanced RELM beta expression in colon cancer patients and suggest that further investigation is warranted to explore the role of RELM beta in colon cancer.

Two-Staged Versus Three-Staged Laparoscopic Anorectoplasty for Patients with Rectoprostatic and Bladder Neck Fistulas: A Comparative Study.

Purpose: To compare the results of two- versus three-staged laparoscopic anorectoplasty (LARP) in children with rectoprostatic and bladder neck fistulas. Materials and Methods: The present study was retrospectively initiated among 32 consecutive patients who underwent two-staged LARP from October 2010 to December 2012. The associated defects, age at the operation, operative time, complications, length of the postoperative hospital stay, total hospitalization cost, and functional results (according to the Krickenbeck scoring system) were evaluated. The results were compared with those of 19 cases who underwent three-staged LARP from October 2008 to September 2010. Results: The average age at the second operation was 4.5 ± 1.2 months in the two-staged group, and 4.2 ± 1.3 months in the three-staged group. In the two-staged group, there were statistically shorter overall operative time and postoperative hospital stay duration. Also, a significantly lower total hospitalization cost was achieved. There was no anastomotic leak in either group. The rates of perineal wound infection, recurrent fistula, and rectal prolapse were 3.85% versus 0% (P = 1.000), 0% versus 5.3% (P = .422), and 11.5% versus 15.8% (P = .686), respectively (two-staged versus three-staged group). The median follow-up time was 67 (range, 54-80) months and 88 (range, 81-104) months, respectively. No significant difference in functional outcome was observed. Conclusions: Two-staged LARP is feasible, safe, and more cost-effective, with comparable incidences of complications and functional outcomes with respect to a three-staged procedure.

EZH2 promotes hepatocellular carcinoma progression through modulating miR-22/galectin-9 axis.

BACKGROUND: Recent studies have shown that interferon-γ (IFN-γ)-induced galectin-9 expression in Kupffer cells plays an essential role in modulatingthe microenvironment of hepatitis-associated hepatocellular carcinoma (HCC). However, whether or not IFN-γ induces galectin-9 expression in HCC cells, its biological role and regulatory mechanism in HCC development and progression are poorly defined. METHODS: Quantitative PCR and western blotting analysis were used to detect galectin-9 and EZH2 levels in HCC cell lines stimulated with IFN-γ. Bioinformatics analysis and luciferase reporter assay were utilized to confirmthe binding ofmiR-22 to the 3' untranslated region (3'-UTR) of galectin-9. The methylation status of miR-22 promoter was analyzed by MSP (Methylation specific PCR) and BSP (bisulfite sequencing PCR), while chromatin immunoprecipitation (ChIP) assay identify the occupation status of EZH2 and H3K27me3 at the promoter. Furthermore, the effect of ectopic expression of galectin-9 and miR-22 on cell proliferation, migration, invasion and cell apoptosis was assessed by using CCK-8, transwell assays and flow cytometric analysis, respectively. RESULTS: IFN-γ induces up-regulation of galectin-9 and EZH2 in HCC cell lines. Galectin-9 is a target of miR-22 and EZH2 facilitates galectin-9 expression by tri-methylation of H3K27 on miR-22 promoter but not hyper-methylation status of DNA. MiR-22 overexpression suppressed HCC cell growth, invasion, and metastasis both in vitro and in vivo. Interestingly, galectin-9 also exhibited antitumor effects, and restoring galectin-9 expression in miR-22 overexpressing cells strengthened its antitumor effects. CONCLUSIONS: These findings indicated that EZH2 facilitates galectin-9 expression by epigenetically repressing miR-22 and that galectin-9, which is known as an immunosuppressant, also functions as a tumor suppressor in HCC.