Breeding of high-tolerance yeast by adaptive evolution and high-gravity brewing of mutant.

BACKGROUND: Ethanol and osmotic stresses are the major limiting factors for brewing strong beer with high-gravity wort. Breeding of yeast strains with high osmotic and ethanol tolerance and studying very-high-gravity (VHG) brewing technology is of great significance for brewing strong beer. RESULTS: This study used an optimized microbial microdroplet culture (MMC) system for adaptive laboratory evolution (ALE) of Saccharomyces cerevisiae YN81 to improve its tolerance to osmotic and ethanol stress. Meanwhile, we investigated the VHG and VHG with added ethanol (VHGAE) brewing processes for the evolved mutants in brewing strong beer. The results showed that three evolved mutants were obtained; among them, the growth performance of YN81mc-8.3 under 300, 340, 380, 420 and 460 g L-1 sucrose stresses was greater than that of the other strains. The ethanol tolerance of YN81mc-8.3 was 12%, which was 20% higher than that of YN81. During strong-beer brewing in a 100 L cylindrical cone-bottom tank, the sugar utilization and ethanol yield of YN81mc-8.3 outperformed those of YN81 in both the VHG and VHGAE brewing processes. Measurement of the diacetyl concentration showed that YN81mc-8.3 had a stronger diacetyl reduction ability; in particular, the real degree of fermentation of beers brewed by YN81mc-8.3 in VHG and VHGAE brewing processes was 75.35% and 66.71%, respectively - higher than those of the two samples brewed by YN81. Meanwhile, the visual, olfactive and gustative properties of the strong beer produced by YN81mc-8.3 were better than those of the other beers. CONCLUSION: In this study, the mutant YN81mc-8.3 and the VHGAE brewing process were optimal and represented a better alternative strong-beer brewing process. © 2023 Society of Chemical Industry.

Functional polymorphisms of the TET1 gene increase the risk of neuroblastoma in Chinese children.

Common genetic mutations are absent in neuroblastoma, one of the most common childhood tumours. As a demethylase of 5-methylcytosine (m5C) modification, TET1 plays an important role in tumourigenesis and differentiation. However, the association between TET1 gene polymorphisms and susceptibility to neuroblastoma has not been reported. Three TET1 gene polymorphisms (rs16925541 A > G, rs3998860 G > A and rs12781492 A > C) in 402 Chinese patients with neuroblastoma and 473 cancer-free controls were assessed using TaqMan. Multivariate logistic regression analysis was used to evaluate the association between TET1 gene polymorphisms and susceptibility to neuroblastoma. The GTEx database was used to analyse the impact of these polymorphisms on peripheral gene expression. The relationship between gene expression and prognosis was analysed using Kaplan-Meier analysis with the R2 platform. We found that both rs3998860 G > A and rs12781492 A > C were significantly associated with increased neuroblastoma risk. Stratified analysis further showed that rs3998860 G > A and rs12781492 A > C significantly increased neuroblastoma risk in certain subgroups. In the combined risk genotype model, 1-3 risk genotypes significantly increased risk of neuroblastoma compared with the 0 risk genotype. rs3998860 G > A and rs12781492 A > C were significantly associated with increased STOX1 mRNA expression in adrenal and whole blood, and high expression of STOX1 mRNA in adrenal and whole blood was significantly associated with worse prognosis. In summary, TET1 gene polymorphisms are significantly associated with increased neuroblastoma risk; further research is required for the potential mechanism and therapeutic prospects in neuroblastoma.

Production of surfactant-stable keratinase from Bacillus cereus YQ15 and its application as detergent additive.

BACKGROUND: With the growing concern for the environment, there are trends that bio-utilization of keratinous waste by keratinases could ease the heavy burden of keratinous waste from the poultry processing and leather industry. Especially surfactant-stable keratinases are beneficial for the detergent industry. Therefore, the production of keratinase by Bacillus cereus YQ15 was improved; the characterization and use of keratinase in detergent were also studied. RESULTS: A novel alkaline keratinase-producing bacterium YQ15 was isolated from feather keratin-rich soil and was identified as Bacillus cereus. Based on the improvement of medium components and culture conditions, the maximum keratinase activity (925 U/mL) was obtained after 36 h of cultivation under conditions of 35 °C and 160 rpm. Moreover, it was observed that the optimal reacting temperature and pH of the keratinase are 60 °C and 10.0, respectively; the activity was severely inhibited by PMSF and EDTA. On the contrary, the keratinase showed remarkable stability in the existence of the various surfactants, including SDS, Tween 20, Tween 60, Tween 80, and Triton X-100. Especially, 5% of Tween 20 and Tween 60 increased the activity by 100% and 60%, respectively. Furtherly, the keratinase revealed high efficiency in removing blood stains. CONCLUSION: The excellent compatibility with commercial detergents and the high washing efficiency of removing blood stains suggested its suitability for potential application as a bio-detergent additive.

Gene cloning and molecular characterization of a thermostable chitosanase from Bacillus cereus TY24.

BACKGROUND: An important conceptual advance in health and the environment has been recognized that enzymes play a key role in the green processing industries. Of particular interest, chitosanase is beneficial for recycling the chitosan resource and producing chitosan oligosaccharides. Also, chitosan gene expression and molecular characterization will promote understanding of the biological function of bacterial chitosanase as well as explore chitosanase for utilizing chitosan resources. RESULTS: A chitosanase-producing bacterium TY24 was isolated and identified as Bacillus cereus. Moreover, the chitosanase gene was cloned and expressed in Escherichia coli. Sequence analysis reveals that the recombinant chitosanase (CHOE) belongs to the glycoside hydrolases 8 family. The purified CHOE has a molecular weight of about 48 kDa and the specific activity of 1150 U/mg. The optimal pH and temperature of CHOE were 5.5 and 65 °C, respectively. The enzyme was observed stable at the pH range of 4.5-7.5 and the temperature range of 30-65 °C. Especially, the half-life of CHOE at 65 °C was 161 min. Additionally, the activity of CHOE was remarkably enhanced in the presence of Mn2+, Cu2+, Mg2+ and K+, beside Ca2+ at 5 mM. Especially, the activity of CHOE was enhanced to more than 120% in the presence of 1% of various surfactants. CHOE exhibited the highest substrate specificity toward colloid chitosan. CONCLUSION: A bacterial chitosanase was cloned from B. cereus and successfully expressed in E. coli (BL21) DE3. The recombinant enzyme displayed good stability under acid pH and high-temperature conditions.

Novel processing strategies to enhance the bioaccessibility and bioavailability of functional components in wheat bran.

Dietary fiber, polysaccharides and phenols are the representative functional components in wheat bran, which have important nutritional properties and pharmacological effects. However, the most functional components in wheat bran exist in bound form with low bioaccessibility. This paper reviews these functional components, analyzes modification methods, and focuses on novel solid-state fermentation (SSF) strategies in the release of functional components. Mining efficient microbial resources from traditional fermented foods, exploring the law of material exchange between cell populations, and building a stable self-regulation co-culture system are expected to strengthen the SSF process. In addition, emerging biotechnology such as synthetic biology and genome editing are used to transform the mixed fermentation system. Furthermore, combined with the emerging physical-field pretreatment coupled with SSF strategies applied to the modification of wheat bran, which provides a theoretical basis for the high-value utilization of wheat bran and the development of related functional foods and drugs.

Association between lncRNA-H19 polymorphisms and hepatoblastoma risk in an ethic Chinese population.

H19 polymorphisms are associated with increased susceptibility to several cancers; however, their role in hepatoblastoma remains unclear. In this study, we investigated the association between three H19 polymorphisms (rs2839698 G>A, rs3024270 C>G, rs217727 G>A) and hepatoblastoma susceptibility in 213 hepatoblastoma patients. The rs2839698 and rs3024270 polymorphisms were associated with significantly increased hepatoblastoma risk, with the GG genotype associated with a higher risk of hepatoblastoma than the CC genotype at the rs3024270 locus. The rs217727 polymorphism was associated with significantly decreased hepatoblastoma risk, with the AG genotype associated with a lower risk of hepatoblastoma than the GG genotype. These findings were confirmed by combined analysis, and stratification analysis revealed that age, gender and clinical stage were associated with increased hepatoblastoma susceptibility. The GGG and AGG haplotypes were significantly associated with increased hepatoblastoma risk compared with the GCA reference (rs2839698, rs3024270, rs217727). The rs2839698 and rs3024270 polymorphisms correlated with decreased MRPL23-AS1 expression, whereas the rs217727 polymorphism was associated with increased MRPL23-AS1 expression. Overall, the H19 rs2839698, rs3024270 and rs217727 polymorphisms were associated with hepatoblastoma susceptibility in a Chinese Han population.

Association of MYC gene polymorphisms with neuroblastoma risk in Chinese children: A four-center case-control study.

BACKGROUND: Neuroblastoma is one of the most common malignant tumors in childhood. Polymorphisms in proto-oncogene MYC are implicated in many cancers, although their role in neuroblastoma remains unclear. In the present study, we attempted to investigate the association between MYC gene polymorphisms and neuroblastoma susceptibility in Chinese children. METHODS: We included two MYC polymorphisms (rs4645943 and rs2070583) and assessed their effects on neuroblastoma risk in 505 cases and 1070 controls via the Taqman method. RESULTS: In single and combined locus analysis, no significant association was found between the two selected polymorphisms and neuroblastoma susceptibility. In stratification analysis, the rs4645943 CT/TT genotypes were significantly associated with a decreased neuroblastoma risk in subjects with tumors originating from other sites [adjusted odds ratio (OR) = 0.42, 95% confidence interval (CI) = 0.21-0.84, p = 0.013]. Meanwhile, the presence of one or two protective genotypes was significantly associated with a decreased neuroblastoma risk in subjects with tumors arising from other sites (adjusted OR = 0.50, 95% CI = 0.26-0.96, p = 0.036). CONCLUSIONS: The present study indicates that MYC gene polymorphisms may have a weak effect on the neuroblastoma risk, which neeeds to be verified further.

Analysis of Clinical Characteristics, Pathological Changes and Changes of Interleukin-6 (IL-6) and C-Reactive Protein (CRP) in Children with Castleman's Disease.

BACKGROUND The aim of this study was to analyze the pathological changes, clinical characteristics and changes in immunity, interleukin-6 (IL-6) and C-reactive protein (CRP) in children with Castleman's disease (CD). MATERIAL AND METHODS A total of 15 CD child patients were enrolled as observation group, while 20 normal children receiving healthy examination were enrolled as healthy control group. The pathological changes, clinical characteristics and changes in immunity and serum IL-6 and CRP expressions were retrospectively analyzed in observation group. RESULTS The clinical manifestation of unicentric CD (UCD) was mainly enlargement of cervical lymph nodes without liver-spleen enlargement and fever, and the major pathological type was the hyaline-vascular type. Multicentric CD (MCD) child patients all had anemia, fever and other systemic symptoms, and the major pathological type was the plasma-cell type. There were expressions of the immune indexes, including cluster of differentiation 3 (CD3), CD4, CD8, CD20, and CD79, in a certain degree, while CD138 and VS38C expressions displayed the polyclonal proliferation of plasma cells, rather than neoplastic proliferation. The Epstein-Barr virus and human herpes virus-8 detection results were negative, and CD21 in follicular dendritic cells in abnormal germinal center was positive. The expression levels of serum IL-6 and CRP in observation group were higher than those in control group (P.

Outcomes of children with hepatoblastoma who underwent liver resection at a tertiary hospital in China: a retrospective analysis.

BACKGROUND: To report the outcomes of hepatoblastoma resected in our institution. METHODS: We diagnosed 135 children with hepatoblastoma at our institution between January 2010 and December 2017. Patients who underwent liver resection were included for analysis. However, patients who abandoned treatment after diagnosis were excluded from analysis, but their clinical characteristics were provided in the supplementary material. RESULTS: Forty-two patients abandoned treatment, whereas 93 patients underwent liver resection and were included for statistical analysis. Thirty-six, 23, 3, and 31 patients had PRETEXT stages II, III, IV, and unspecified tumours, respectively. Seven patients had ruptured tumour; 9 had lung metastasis (one patient had portal vein thrombosis concurrently). Sixteen patients underwent primary liver resection; 22, 25, and 30 patients received cisplatin-based neoadjuvant chemotherapy and delayed surgery, preoperative transarterial chemoembolization (TACE) and delayed surgery, and a combination of cisplatin-based neoadjuvant chemotherapy, TACE, and delayed surgery, respectively. Forty patients had both PRETEXT and POST-TEXT information available for analysis. Twelve patients were down-staged after preoperative treatment, including 2, 8, and 2 patients from stages IV to III, III to II, and II to I, respectively. Ten patients with unspecified PRETEXT stage were confirmed to have POST-TEXT stages II (n = 8) and I (n = 2) tumours. Seven tumours were associated with positive surgical margins, and 12 patients had microvascular involvement. During a median follow-up period of 30.5 months, 84 patients survived without relapse, 9 experienced tumour recurrence, and 4 died. The 2-year event-free survival (EFS) and overall survival (OS) rates were 89.4 ± 3.4%, and 95.2 ± 2.4%, respectively; they were significantly better among patients without metastasis (no metastasis vs metastasis: EFS, 93.5 ± 3.7% vs 46.7 ± 19.0%, adjusted p = 0.002. OS, 97.6 ± 2.4% vs 61.0 ± 18.1%, adjusted p = 0.005), and similar among patients treated with different preoperative strategies (chemotherapy only vs TACE only vs Both: EFS, 94.7 ± 5.1% vs 91.7 ± 5.6% vs 85.6 ± 6.7%, p = 0.542. OS, 94.1 ± 5.7% vs 95.7 ± 4.3% vs 96.7 ± 3.3%, p = 0.845). CONCLUSION: The OS for patients with hepatoblastoma who underwent liver resection was satisfactory. Neoadjuvant chemotherapy and TACE seemed to have a similar effect on OS. However, the abandonment of treatment by patients with hepatoblastoma was common, and may have biased our results.

Liver biopsy for hepatoblastoma: a single institution's experience.

BACKGROUND/PURPOSE: Hepatoblastoma diagnoses require liver biopsies. We aimed to investigate factors affecting the success of liver biopsy for hepatoblastoma diagnoses. METHODS: Data from patients with hepatoblastoma, including their demographic and clinical data, biopsy procedure information, pathologic diagnoses and subclassification, and surgical complications, were retrospectively reviewed. RESULTS: Of 153 patients who underwent liver biopsy, 28, 93, and 31 underwent computed tomography-guided, digital subtraction angiography-guided, and ultrasound-guided percutaneous biopsies, respectively, and one underwent a laparoscopic liver biopsy. One patient developed postoperative bleeding requiring a blood transfusion. The median number of specimens collected was 3. One-hundred and forty-four (94.1%) patients' HB diagnoses were confirmed through biopsies, and 96 (62.7%) patients' HB diagnoses were subclassified. Seven surgeons and eight interventional radiologists performed the biopsies. The diagnostic success rate did not correlate with the biopsy technique or the specialist who performed the biopsy. Significantly more specimens were biopsied from the patients whose diagnoses were subclassified (3.34 ± 1.08) than from those whose diagnoses were not subclassified (2.81 ± 0.79). Surgeons tended to collect more specimens than the interventional radiologists. CONCLUSION: Percutaneous liver biopsy is safe and effective for diagnosing hepatoblastoma, and its complication rate is very low. Collecting >3 pieces of tissue is preferred. LEVEL OF EVIDENCE: III.

Targeting ß3-adrenergic receptor signaling inhibits neuroblastoma cell growth via suppressing the mTOR pathway.

Neuroblastoma (NB), the most common extracranial solid tumor in childhood, always leads to an unfavorable prognosis. ß3-adrenergic receptor (ß3-AR) signaling plays an important role in lipid metabolism. Although previous studies have focused mainly on the role of ß2-AR in tumor cells; there are few studies about the cancer-related function of ß3-AR. Herein, we showed that ß3-AR expression was significantly increased in clinical NB tissue compared with that in the less malignant ganglioneuroma (GN) and ganglioneuroblastoma (GNB) tissues. Further cellular assays demonstrated that treatment of NB cells with SR59230A (a specific ß3-AR antagonist) suppressed NB cells growth and colony formation, and siRNA knockdown of ß3-AR expression also inhibited NB cell proliferation. The mechanistic study revealed that ß3-AR knockdown and SR59230A inhibited the phosphorylation and thereby the activation of the mTOR/p70S6K pathway. Activation of the mTOR pathway with the activator MHY1485 reversed the inhibitory effect of SR59230A on NB cell growth. Above all, our study clarifies a novel regulatory role of ß3-AR in NB cell growth and provides a potent therapeutic strategy for this disease by specific targeting of the ß3-AR pathway.

Impact of 3D printing technology on the comprehension of surgical liver anatomy.

BACKGROUND AND AIMS: Surgical planning in liver resection depends on the precise understanding of the three-dimensional (3D) relation of tumors to the intrahepatic vascular trees. This study aimed to investigate the impact of 3D printing (3DP) technology on the understanding of surgical liver anatomy. METHODS: We selected four hepatic tumors that were previously resected. For each tumor, a virtual 3D reconstruction (VIR) model was created from multi-detector computed tomography (MDCT) and was prototyped using a 3D printer. Forty-five surgical residents were evenly assigned to each group (3DP, VIR, and MDCT groups). After evaluation of the MDCT scans, VIR model, or 3DP model of each tumor, surgical residents were asked to assign hepatic tumor locations and state surgical resection proposals. The time used to specify the tumor location was recorded. The correct responses and time spent were compared between the three groups. RESULTS: The assignment of tumor location improved steadily from MDCT, to VIR, and to 3DP, with a mean score of 34.50, 55.25, and 80.92, respectively. These scores were out of 100 points. The 3DP group had significantly higher scores compared with other groups (p < 0.001). Furthermore, 3DP significantly improved the accuracy of surgical resection proposal (p < 0.001). The mean accuracy of the surgical resection proposal for 3DP, VIR, and MDCT was 57, 25, and 25%, respectively. The 3DP group took significantly less time, compared with other groups (p < 0.005). The mean time spent on assessing the tumor location for 3DP, VIR, and MDCT groups was 93, 223, and 286 s, respectively. CONCLUSIONS: 3D printing improves the understanding of surgical liver anatomy for surgical residents. The improved comprehension of liver anatomy may facilitate laparoscopy or open liver resection.

The rs2147578 C > G polymorphism in the Inc-LAMC2-1:1 gene is associated with increased neuroblastoma risk in the Henan children.

BACKGROUND: The rs2147578 C > G polymorphism in the long non-coding RNA gene Lnc-LAMC2-1:1 is associated with increased susceptibility to a few types of cancers. However, its role in neuroblastoma has not been evaluated yet. METHODS: We investigated the association between the lnc-LAMC2-1:1 rs2147578 C > G polymorphism and neuroblastoma susceptibility in Chinese Han populations. A total of 393 neuroblastoma cases and 812 healthy individuals from the Henan and Guangdong provinces were enrolled and subjected to genotyping. Odds ratio (OR) and 95% confidence interval (CI) were used to determine the strength of the association of interest. RESULTS: Combined analysis revealed that the lnc-LAMC2-1:1 rs2147578 C > G polymorphism was associated with increased neuroblastoma susceptibility (CG vs. CC: adjusted OR = 1.33, 95% CI = 1.01-1.75, P = 0.045; CG/GG vs. CC: adjusted OR = 1.34, 95% CI = 1.03-1.74, P = 0.028). In stratification analysis, children under 18 months with rs2147578 CG/GG genotypes had an increased neuroblastoma risk (adjusted OR = 1.70, 95% CI = 1.08-2.67, P = 0.022). Females with rs2147578 CG/GG genotypes also had increased neuroblastoma susceptibility (adjusted OR = 2.08, 95% CI = 1.37-3.18, P = 0.0007). In addition, children with lnc-LAMC2-1:1 rs2147578 CG/GG genotypes were prone to develop earlier stages of neuroblastoma (adjusted OR = 1.46, 95% CI = 1.01-2.12, P = 0.046). CONCLUSIONS: The Lnc-LAMC2-1:1 rs2147578 C > G polymorphism may contribute to increased neuroblastoma susceptibility in children of Henan province.

Impact of 3D Printing Technology on Comprehension of Surgical Anatomy of Retroperitoneal Tumor.

OBJECTIVES: To investigate the impact of 3D printed model on understanding of surgical anatomy of retroperitoneal tumor. MATERIALS AND METHODS: Three-dimensional model was printed, based on multi-detectors computed tomography (MDCT) of a retroperitoneal tumor. Participants (10 students, 10 residents and 10 surgeons) were asked to identify vasculatures which were important in resection of the tumor, after viewing MDCT images, 3D visualization model and 3D printed model, respectively. Regarding this tumor, left renal vein (LRV), right renal pedicles (RRP) and inferior vena cava (IVC) were chosen as indicators to assess participants' performances. Identification of vasculatures was evaluated and a score was given (1 point = success; 0 point = failure). The total number and percentage of correct identification were used to measure how these three types of anatomic presentation were able to transfer in terms of anatomical recognition. Recorded data were analyzed both pooling together data from three groups of participants and separately for each group. RESULTS: In analysis of overall comparison among 3D printing, 3D visualization and MDCT, recognition of all three vasculatures simultaneously was 83.33, 73.33 and 46.67%, respectively (P = 0.007); recognition of LRV was 90, 80 and 63.33% (P = 0.043), respectively; recognition of RRP was 96.67, 83.33 and 73.33% (P = 0.035), respectively; recognition of IVC was 93.33, 90 and 80% (P = 0.366), respectively. In subgroup analysis of performances of three groups of participants, no significant differences regarding anatomic recognition were observed among MDCT, 3D visualization and 3D printed model for each group of participants. CONCLUSION: Three-dimensional printed model improved the understanding of surgical anatomy of retroperitoneal tumor.

Neonatal Gastric Perforation: Case Series and Literature Review.

PURPOSE: We reported clinical findings of neonatal gastric perforation in a tertiary children's hospital. PATIENTS AND METHODS: Retrospective chart reviews were conducted for neonatal gastric perforation between 1980 and 2016. Factors including sex, gestational age, birth weight, age, main symptoms and signs, white blood cell count (WBC), surgical intervention time (time between development of main symptom and surgical intervention), surgical findings, pathologic results, clinical outcomes, and causes of death were collected. RESULTS: Sixty-eight patients were identified. In total, 76.5% were male infants, the median age was 4 days, median birth weight was 2500 g, and 42.6% were premature. Abdominal distention and vomiting were the most common symptoms, and pneumoperitoneum was the most common radiographic finding. The median surgical intervention time was 51 h (range 8-312). In total, 73.5% of perforations occurred in the great curvature, 17.6% in the lesser curvature, and 8.9% unspecified. The median perforation size was 4 cm (range 0.2-16). Associated gastrointestinal anomalies were found in 20.6% of patients, and the most common anomaly was intestinal malrotation. Of the 51 patients with pathologic results, 11 showed the presence of musculature in the perforated gastric wall, while 40 showed the absence of musculature. Of the 66 patients with known clinical outcomes, 26 (39.4%) died, 23 of who died of infection. Among those aforementioned factors, WBC has a significant impact on survival. The mortality for four arbitrary divided year groups (1980-1989, 1990-1999, 2000-2009, and 2010-2016) was 100, 50, 31.6, and 16.7%, respectively. CONCLUSIONS: The mortality of neonatal gastric perforation is constantly decreasing. Associated gastrointestinal anomalies and the presence of musculature are found in a minority of this condition.

Surgical management and outcomes of ganglioneuroma and ganglioneuroblastoma-intermixed.

PURPOSE: Clinical researches about the management and outcomes of ganglioneuroma and ganglioneuroblastoma-intermixed are limited. We report the surgical outcomes of ganglioneuroma and ganglioneuroblastoma-intermixed in a single institution. METHODS: Ganglioneuroma and ganglioneuroblastoma-intermixed diagnosed and resected between May 2009 and May 2015 in a tertiary children's hospital were retrospectively reviewed. Patients' demographic data, INSS stage, surgical complications, residual tumor size and outcomes were collected. RESULTS: Thirty-four patients were included in the current study. All had localized tumors and were surgically managed. The overall acute complications rates were 8.8% (3/34) and none were fatal. Thirty-three of 34 patients had at least macroscopic tumor resection. Six patients had radiographically detected residual tumor after surgery, 25 none and 3 undocumented. Thirty-three (97.1%) patients were alive during a median follow-up of 36 months (range 1-82). In subgroup analysis, no significant difference regarding surgical complications and survival was found between ganglioneuroma and ganglioneuroblastoma-intermixed. Increased complete resection rates were observed in thoracic tumor compared with abdominal ones (p = 0.03). However, no significant difference (p = 0.089) regarding overall survival was found between patients with residual tumors and those without. Of the six patients with residual tumors, three showed complete resolution, two were unchanged and one died 3 years after initial surgery (the only death in this study). CONCLUSION: Ganglioneuroma and ganglioneuroblastoma-intermixed can be safely and effectively resected, the residual tumor seems not to influence overall survival.

Potentially functional polymorphisms in the LIN28B gene contribute to neuroblastoma susceptibility in Chinese children.

UNLABELLED: Neuroblastoma is the most commonly diagnosed solid tumour outside the central nervous system in children. However, genetic factors underlying neuroblastoma remain largely unclear. Previous genome-wide association study indicated that lin-28 homolog B (LIN28B) might play an important role in the development of neuroblastoma and also contributed to its poor overall survival. With the purpose to evaluate the association between LIN28B gene polymorphisms and neuroblastoma susceptibility in Southern Chinese population, we conducted this study with 256 neuroblastoma cases and 531 cancer-free controls. Four potentially functional polymorphisms (rs221634 A>T, rs221635 T>C, rs314276 C>A and rs9404590 T>G) were genotyped using Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the associations between the selected single nucleotide polymorphisms (SNPs) and neuroblastoma susceptibility. We also performed genotype-phenotype association analysis to explore the effects of the selected SNPs on LIN28B gene transcripts. Our results indicated that the rs221634 TT genotype was associated with an increased neuroblastoma risk (TT versus AA/AT: adjusted OR = 1.50, 95% CI = 1.04-2.17). The association was more pronounced in males, patients with tumour of mediastinum origin, as well as patients in early clinical stages. Moreover, overall analysis and stratified analysis also showed an increased risk of neuroblastoma for carrier of the 2-4 risk genotypes. In summary, these results indicated that the LIN28B rs221634 A>T polymorphism was associated with an increased neuroblastoma risk in Southern Chinese children. These findings need further validation in large studies with different ethnicities involved.

Association of potentially functional variants in the XPG gene with neuroblastoma risk in a Chinese population.

XPG gene plays a critical role in the nucleotide excision repair pathway. However, the association between XPG gene polymorphisms and neuroblastoma risk has not been investigated. In this study with 256 neuroblastoma cases and 531 cancer-free controls, we investigated the effects of five potentially functional polymorphisms (rs2094258 C>T, rs751402 C>T, rs2296147 T>C, rs1047768 T>C and rs873601G>A) on neuroblastoma risk. We calculated odds ratio (OR) and 95% confidence interval (CI) to evaluate the association between the five selected polymorphisms and neuroblastoma risk. False-positive report probability (FPRP) was utilized to determine whether significant findings were noteworthy or because of a chance. We also performed genotype-phenotype association analysis to explore the biological plausibility of our findings. We found that the rs2094258 T allele was significantly associated with decreased neuroblastoma risk (CT versus CC: adjusted OR = 0.65, 95% CI = 0.47-0.90, P = 0.010; and CT/TT versus CC: adjusted OR = 0.71, 95% CI = 0.53-0.97, P = 0.030) after adjusting for age and gender. The association was more prominent for subjects with retroperitoneal tumour or early-stage tumour. We also found that carriers of the 2-3 risk genotypes had a significantly increased neuroblastoma risk when compared to carriers of the 0-1 risk genotypes. The association with risk genotypes was more predominant in older children, females and subjects with retroperitoneal tumour or early stage. Our results were further supported by FPRP analysis and genotype-phenotype association analysis. In conclusion, our study verified that the XPG gene rs2094258 C>T polymorphism may contribute to neuroblastoma susceptibility. Our findings require further validation by studies with larger sample size and concerning different ethnicities.

Evaluation of GWAS-identified SNPs at 6p22 with neuroblastoma susceptibility in a Chinese population.

Previous genome-wide association studies (GWASs) have reported that three single nucleotide polymorphisms (SNPs) (rs6939340 A>G, rs4712653 T>C, and rs9295536 C>A) located at 6p22 locus were associated with neuroblastoma susceptibility for Caucasian descent. We conducted this hospital-based case-control study with 201 neuroblastoma patients and 531 controls to investigate the association between these three SNPs in the FLJ22536 gene with neuroblastoma susceptibility in the Chinese Han population. The odds ratio (OR) and 95 % confidence interval (CI) were calculated to estimate the strength of the association using unconditional logistic regression model. We found that the rs6939340 A allele carriers were associated with significantly decreased neuroblastoma susceptibility (AG vs. GG: adjusted OR = 0.54, 95 % CI = 0.38-0.77; AA vs. GG: adjusted OR = 0.49, 95 % CI = 0.25-0.93; and AA/AG vs. GG: adjusted OR = 0.53, 95 % CI = 0.38-0.74) after adjustment for age and gender. The protective association between variant allele and neuroblastoma susceptibility was also observed for the rs4712653 and rs9295536 polymorphisms. Moreover, we found that subjects carrying one or more protective genotypes had a much lower neuroblastoma susceptibility than non-carriers (adjusted OR = 0.60, 95 % CI = 0.43-0.83). Our study verified that the associations between all of the three SNPs in the 6p22 locus are associated with neuroblastoma susceptibility in the Chinese subjects. Further prospective multicenter studies with different ethnicities and larger sample size are needed to validate our findings.

The Association between GWAS-identified BARD1 Gene SNPs and Neuroblastoma Susceptibility in a Southern Chinese Population.

A previous genome-wide association study (GWAS) has found that some common variations in the BARD1 gene were associated with neuroblastoma susceptibility especially for high-risk subjects, and the associations have been validated in Caucasians and African-Americans. However, the associations between BARD1 gene polymorphisms and neuroblastoma susceptibility have not been studied among Asians, not to mention Chinese subjects. In the present study, we investigated the association of three BARD1 polymorphisms (rs7585356 G>A, rs6435862 T>G and rs3768716 A>G) with neuroblastoma susceptibility in 201 neuroblastoma patients and 531 controls using TaqMan methodology. Overall, none of these polymorphisms was significantly associated with neuroblastoma susceptibility. However, stratified analysis showed a more profound association between neuroblastoma risk and rs6435862 TG/GG variant genotypes among older children (adjusted OR=1.55, 95% CI=1.04-2.31), and children with adrenal gland-originated disease (adjusted OR=2.94, 95% CI=1.40-6.18), or with ISSN clinical stages III+IV disease (adjusted OR=1.75, 95% CI=1.09-2.84). Similar results were observed for the variant genotypes of rs3768716 A>G polymorphism among these three subgroups. Our results suggest that the BARD1 rs6435862 T>G and rs3768716 A>G polymorphisms may contribute to increased susceptibility to neuroblastoma, especially for the subjects at age ≥12 months, with adrenal gland-originated or with late clinical stage neuroblastoma. These findings need further validation by prospective studies with larger sample size with subjects enrolled from multicenter, involving different ethnicities.