Correlation of DNA load, genotyping, and clinical phenotype of Mycoplasma pneumoniae infection in children.

Introduction: This study aimed to investigate the correlation between Mycoplasma pneumoniae (MP)-DNA load in the bronchoalveolar lavage fluid (BALF) of children with MP pneumonia (MPP) and its subtypes, relevant laboratory data, imaging, extrapulmonary complications in infected children, and its clinical significance in evaluating the disease. Methods: Children hospitalized with MPP at Tianjin Children's Hospital between December 2017 and December 2020 were selected for the study, excluding those with mixed viral, bacterial, and fungal infections. Children were divided into low- and high-load groups according to the MP DNA load in BALF using real-time quantitative fluorescence polymerase chain reaction (PCR). After a successful MP culture, positive specimens were subjected to PCR-Restriction fragment length polymorphism and Multiple-locus variable number tandem repeat analysis typing. Basic data, clinical information, laboratory data, and radiological results were collected from all children included in the study. Results: The PI-I type dominated the different load groups. Children in the low-load group had more wheezing and shortness of breath; however, children in the high-load group had a higher length of hospitalization, maximum fever temperature, higher chills/chilliness, incidence of abdominal pain, and higher C-reactive protein (CRP), procalcitonin (PCT) and aspartate aminotransferase (AST) levels. Children in the high-load group were more likely to have imaging changes such as pleural effusion, and the incidence of respiratory infections and extrapulmonary complications was higher than that of those in the low-load group. We applied Spearman's correlation analysis to clarify the relationship between MP DNA load and the clinical severity of MPP. We found that MP DNA load was positively correlated with length of hospitalization, maximum fever temperature, CRP, PCT, Interleukin-6 (IL-6), and AST levels, and negatively correlated with fever and cough durations, white blood cell count (WBC), and proportion of monocytes (MONO). The degree of correlation was as follows: length of hospitalization > IL-6 > cough duration > AST > fever duration > PCT > WBC > proportion of MONO > maximum fever temperature > CRP levels. Conclusions: MP DNA load was not correlated with MP typing but was significantly correlated with the children's clinical phenotype. Therefore, the MP DNA load helps in the early diagnosis of infection and can better predict disease regression.

Genistein prevents the production of hypospadias induced by Di-(2-ethylhexyl) phthalate through androgen signaling and antioxidant response in rats.

Environmental estrogen exposure has increased dramatically over the past 50 years. In particular, prenatal exposure to estrogen causes many congenital diseases, among which reproductive system development disorders are extremely serious. In this study, the molecular mechanism of hypospadias and the therapeutic effect of genistein (GEN) were investigated through in vivo models prepared by Di-(2-ethylhexyl) phthalate (DEHP) exposure between 12 and 19 days of gestation. With increased DEHP concentrations, the incidence of hypospadias increased gradually. DEHP inhibited the key enzymes involved in steroid synthesis, resulting in decreasing testosterone synthesis. At the same time, DEHP increased reactive oxygen species (ROS) and produced inflammatory factors via NADPH oxidase-1 (NOX1) and NADPH oxidase-4 (NOX4) pathways. It also inhibited Steroid 5 α Reductase 2 (Srd5α2) and decreased dihydrotestosterone (DHT) synthesis. Additionally, DEHP inhibited the androgen receptor (AR), resulting in reduced DHT binding to the AR that ultimately retarded the development of the external reproductive system. GEN, a phytoestrogen, competes with DEHP for binding to estrogen receptor ß (ERß). This competition, along with GEN's antiestrogen and antioxidant properties, could potentially reverse impairments. The findings of this study provide valuable insights into the role of phytoestrogens in alleviating environmental estrogen-induced congenital diseases.

Identification and Validation of CXCL2 as a Key Gene for Childhood Obesity.

This study aims to identify the key genes and their regulatory networks by bioinformatics, increasing understanding of childhood obesity. The data comes from the GEO and Immport database. The immune microenvironment was explored in GSE104815. Key genes were identified by intersection of DEGs with the immune gene set. Enrichment analysis revealed gene-related functions and correlation analysis explored the relationship. Regulatory networks were constructed based on miRcode, TarBase and TargetScan databases. GSE29718 was used to validate our findings. Intercellular communication and cell differentiation trends were further explored using single-cell data from GSE153643. Based on our research, the immune microenvironment in the obese group showed higher immune infiltration. We found 962 DEGs and CXCL2 was identified as the key gene. The co-regulatory network of lncRNA-miRNA-mRNA suggested that obtaining TM4SF19-AS1, GUSBP11, AC105020.1, LINC00189, COL4A2-AS2, VIPR1-AS1 and LINC00242 may regulate CXCL2 (r > 0.9 and P < 0.01). Differential expression of CXCL2 was validated in GSE29718 (P < 0.05) and CXCL2 was identified as a biomarker for childhood obesity (AUC = 0.885). GSVA enrichment analysis revealed many pathways of high group obtaining the TNF-α signaling via NF-κB pathway and interferon γ response pathway. In GSE153643, 11 cell types were identified and CXCL2 was highly expressed in monocyte, macrophage, endothelial cell and pericyte. In CXCL2 high expressing macrophages, there was a tendency for cells to polarize toward M1 macrophages (P < 0.05). In summary, we identified CXCL2 as a potential biomarker of childhood obesity. The development of childhood obesity may be associated with the activation of immune infiltration of macrophage M1 polarization by CXCL2 expression.

Smoking and alcohol consumption with the risk of 11 common otolaryngological diseases: a bidirectional Mendelian randomization.

PURPOSE: In this study, a bidirectional mendelian randomization was applied to evaluate the association of smoking and alcohol consumption with 11 otolaryngological diseases. METHODS: A total of 85,22,34 and 7 single nucleotide polymorphisms were used as instrumental variables for smoking initiation, cigarettes per day, alcoholic drinks per week and alcohol consumption, respectively. Genetic associations with 11 common otolaryngological diseases were obtained from the UK Biobank and FinnGen dataset. IVW, weighted median, MR-Egger, MR-PRESSO and leave-one-out method were used in this analysis. RESULTS: Smoking initiation increased the risk of vocal cord and larynx diseases (OR 1.002; 95% CI 1.001-1.004; P = 4 × 10-4), head and neck cancer (OR 1.001; 95% CI 0.999-1.003; P = 0.027), thyroid cancer (OR 1.538; 95% CI 1.006-2.351; P = 0.047) and sleep apnoea (OR 1.286; 95% CI 1.099-1.506; P = 0.002). Cigarettes per day was associated with chronic sinusitis (OR 1.152; 95% CI 1.002-1.324; P = 0.046), chronic rhinitis and pharyngitis (OR 1.200; 95% CI 1.033-1.393; P = 0.017), vocal cord and larynx diseases (OR 1.001; 95% CI 0.999-1.002; P = 0.021) and head and neck cancer (OR 1.001; 95% CI 0.999-1.003; P = 0.017). Alcoholic drinks per week only was significantly associated with the risk of head and neck cancer (OR 1.003; 95% CI 1.001-1.006; P = 0.014). However, there was no evidence to support that genetically predicted alcohol consumption increased the risk of otolaryngological diseases. Reverse MR also did not find outcomes effect on exposures. CONCLUSION: This study shows that smoking and heavy alcohol consumption promote the occurrence of some otolaryngological diseases indicating that lifestyle modification might be beneficial in preventing otolaryngological diseases.

The potential effects and mechanism of echinacoside powder in the treatment of Hirschsprung's Disease.

Possible complications, such as intestinal obstruction and inflammation of the intestinal tract, can have a detrimental effect on the prognosis after surgery for Hirschsprung disease. The aim of this study was to investigate the potential targets and mechanisms of action of echinacoside to improve the prognosis of Hirschsprung disease. Genes related to the disease were obtained through analysis of the GSE96854 dataset and four databases: OMIM, DisGeNET, Genecard and NCBI. The targets of echinacoside were obtained from three databases: PharmMapper, Drugbank and TargetNet. The intersection of disease genes and drug targets was validated by molecular docking. The valid docked targets were further explored for their expression by using immunohistochemistry. In this study, enrichment analysis was used to explore the mechanistic pathways involved in the genes. Finally, we identified CA1, CA2, CA9, CA12, DNMT1, RIMS2, RPGRIP1L and ZEB2 as the core targets. Except for ZEB2, which is predominantly expressed in brain tissue, the remaining seven genes show tissue specificity and high expression in the gastrointestinal tract. RIMS2 possesses a high mutation phenomenon in pan-cancer, while a validated ceRNA network of eight genes was constructed. The core genes are involved in several signaling pathways, including the one-carbon metabolic process, carbonate dehydratase activity and others. This study may help us to further understand the pharmacological mechanisms of echinacoside and provide new guidance and ideas to guide the treatment of Hirschsprung disease.

Identification of the molecular subtypes and construction of risk models in neuroblastoma.

The heterogeneity of neuroblastoma directly affects the prognosis of patients. Individualization of patient treatment to improve prognosis is a clinical challenge at this stage and the aim of this study is to characterize different patient populations. To achieve this, immune-related cell cycle genes, identified in the GSE45547 dataset using WGCNA, were used to classify cases from multiple datasets (GSE45547, GSE49710, GSE73517, GES120559, E-MTAB-8248, and TARGET) into subgroups by consensus clustering. ESTIMATES, CIBERSORT and ssGSEA were used to assess the immune status of the patients. And a 7-gene risk model was constructed based on differentially expressed genes between subtypes using randomForestSRC and LASSO. Enrichment analysis was used to demonstrate the biological characteristics between different groups. Key genes were screened using randomForest to construct neural network and validated. Finally, drug sensitivity was assessed in the GSCA and CellMiner databases. We classified the 1811 patients into two subtypes based on immune-related cell cycle genes. The two subtypes (Cluster1 and Cluster2) exhibited distinct clinical features, immune levels, chromosomal instability and prognosis. The same significant differences were demonstrated between the high-risk and low-risk groups. Through our analysis, we identified neuroblastoma subtypes with unique characteristics and established risk models which will improve our understanding of neuroblastoma heterogeneity.

The Gut Microbiota and Inflammatory Factors in Pediatric Appendicitis.

Background: The study analyzed gut microflora's composition and investigated the associations between the associations between gut dysbiosis and inflammatory indicators in pediatric patients with acute appendicitis. Methods: High-throughput sequencing and bioinformatics analysis were used to investigate the composition and diversity of gut microflora in 20 pediatric patients with acute appendicitis and 11 healthy children. Endpoints measured were operational taxonomic units (OTU) of gut microflora. The OTU and its abundance analysis, sample diversity analysis, principal component analysis of samples, differential analysis, and analysis of biomarkers were performed. Results: Overall fecal microbial richness and diversity were similar in patients and controls. Yet richness within the group of Bilophila, Eggerthella, Clostridium, Parvimonas, Megasphaera, Atopobium, Phascolarctobacterium, Adlercreutzia, Barnesiella, Klebsiella, Enterococcus, and Prevotella genera was higher in patients. Adlercreutzia was significantly positively correlated with IL-10, while the three other genera, comprising Klebsiella, Adlercreutzia, and Prevotella, were positively correlated with B cells level. Conclusion: Gut microbiome components are significantly different in pediatric patients with acute appendicitis and healthy children. The differential abundance of some genera is correlated with the production of inflammatory markers in appendicitis.

[Diagnosis and treatment of orbital complications of acute sinusitis in 51 children].

Objective:To analyze the clinical features, diagnosis and treatment of acute sinusitis related orbital cellulitis in children. Methods:The data of 51 cases with acute sinusitis comorbid with orbital cellulitis in Tianjin Children's Hospital from April 2016 to March 2021 were retrospectively analyzed. According to the extent of infection, the patients were divided into two groups:pre-septal orbital cellulitis（7 cases） and post-septal orbital cellulitis（44 cases）. The general clinical characteristics, clinical manifestations, laboratory examination and treatment were compared between the two groups. Among them, 23 cases（6 in pre-septal orbital cellulitis group and 17 in post-septal orbital cellulitis group） were cured by medicine treatment; 28 cases were cured by surgical treatment after failure of medicine treatment. Results:There was no significant difference in age, gender and medical history between the two groups. Redness, swelling, heat and pain in eyelid was the most common clinical manifestations of orbital cellulitis in children, followed by fever, headache, runny nose, eye fixation, and vision loss. WBC count and neutrophils percentage were significantly higher in post-septal orbital cellulitis group. All children were followed up for 3 months to 3 years， 1 case was lost to follow-up， 50 cases had no recurrence and recovered well. Conclusion:Orbital cellulitis is a common and rapid developing complication of sinusitis in children. Early diagnosis and effective anti-infection treatment are very important for prognosis. Orbital CT plays an important role in the determination and evaluation of this complication. When conservative treatment is ineffective, surgical drainage in time can reduce the occurrence of serious ocular sequelae.

Risk factors of postoperative adhesive bowel obstruction in children with complicated appendicitis.

PURPOSE: Postoperative adhesive bowel obstruction (ABO) is a common complication especially in complicated appendicitis. This study aimed to analyze the risk factors for ABO following appendectomy in children with complicated appendicitis, and establish a scoring model for predicting postoperative ABO and treatment option to relieve the obstruction. METHODS: From December 2014 to January 2020, all files of consecutive patients with complicated appendicitis underwent appendectomy were reviewed. Univariate and multivariate analyses were used to screen out the risk factors of postoperative ABO, and establish a scoring model for predicting postoperative ABO and surgical relief to relieve the obstruction. RESULTS: Of the 780 patients, 87 (11.2%) had ABO following appendectomy, including 27 who underwent surgical relief. Age ≤ 6 years, overweight and obesity, duration of symptoms ≥ 36 h, C-reactive protein ≥ 99 mg/L, duration of operation ≥ 60 min, intraoperative peritoneal lavage, and postoperative flatus time ≥ 20 h were independent risk factors for postoperative ABO. The final scoring model for postoperative ABO included factors above, and exhibited a high degree of discrimination (area under the curve [AUC]: 0.937; 95% confidence interval [CI] 0.913-0.960) corresponding to an optimal cut-off value of 6: 82.8% sensitivity, 92.6% specificity. Furthermore, the scoring model showed a sensitivity of 74.1% and a specificity of 91.7% for patients wo underwent surgical relief to relieve obstruction with the optimal cut-off value of 9. CONCLUSION: Risk factors for postoperative ABO should be taken seriously in children with complicated appendicitis. The scoring model is a novel but promising method to predict postoperative ABO and provide reference for clinical decision-making to relieve the obstruction.

A clinical prediction model for complicated appendicitis in children younger than five years of age.

BACKGROUND: No reliably specific method for complicated appendicitis has been identified in children younger than five years of age. This study aimed to analyze the independent factors for complicated appendicitis in children younger than five years of age, develop and validate a prediction model for the differentiation of simple and complicated appendicitis. METHODS: A retrospective study of 382 children younger than five years of age with acute appendicitis from January 2007 to December 2016 was conducted with assessments of demographic data, clinical symptoms and signs, and pre-operative laboratory results. According to intraoperative findings and postoperative pathological results, acute appendicitis was divided into simple and complicated appendicitis. Univariate and multivariate analyses were used to screen out the independent factors of complicated appendicitis, and develop a prediction model for complicated appendicitis. Then 156 such patients from January 2017 to December 2019 were collected as validation sample to validate the prediction model. Test performance of the prediction model was compared with the ALVARADO score and Pediatric Appendicitis Score (PAS). RESULTS: Of the 382 patients, 244 (63.9%) had complicated appendicitis. Age, white blood cell count, and duration of symptoms were the independent factors for complicated appendicitis in children younger than five years of age. The final predication model for complicated appendicitis included factors above. In validation sample, the prediction model exhibited a high degree of discrimination (area under the curve [AUC]: 0.830; 95% confidence interval [CI]: 0.762-0.885) corresponding to a optimal cutoff value of 0.62, and outperformed the PAS (AUC: 0.735; 95% CI: 0.658-0.802), ALVARADO score (AUC: 0.733; 95% CI: 0.657-0.801). CONCLUSION: Age, white blood cell count, and duration of symptoms could be used to predict complicated appendicitis in children younger than five years of age with acute appendicitis. The prediction model is a novel but promising method that aids in the differentiation of acute simple and complicated appendicitis.

Peritoneal irrigation vs suction alone during pediatric appendectomy for perforated appendicitis: A meta-analysis.

BACKGROUND: There currently exists no substantial evidence reporting the efficacy of peritoneal irrigation in reducing the incidence of postoperative intra-abdominal abscess in pediatric patients. The purpose of our study was to perform a meta-analysis to compare rates of intra-abdominal abscess after appendectomy between irrigation and suction alone groups. METHODS: We identified studies by a systematic search in EMBASE, PubMed, Web of Science, and the Cochrane Library to recognize randomized controlled trials and case control studies from the 1950 to May 2019. We limited the English language studies. We checked the reference list of studies to recognize other potentially qualified trials. We analyzed the merged data with use of the Review Manager 5.3. RESULTS: We identified 6 eligible papers enrolling a total of 1633 participants. We found no significant difference in the incidence of postoperative intraabdominal abscess, wound infection, and the length of hospitalization between 2 group, but duration of surgery is longer in irrigation group (MD = 6.76, 95% CI = 4.64 to 8.87, P < .001; heterogeneity, I = 25%, P = .26). CONCLUSION: Our meta-analysis did not provide strong evidence allowing definite conclusions to be drawn, but suggested that peritoneal irrigation during appendectomy did not decrease the incidence of postoperative IAA. This meta-analysis also indicated the need for more high-quality trials to identify methods to decrease the incidence of postoperative IAA in pediatric perforated appendicitis patients.Trial registration number Standardization of endoscopic treatment of acute abdomen in children: 14RCGFSY00150.

Which is the best probiotic treatment strategy to prevent the necrotizing enterocolitis in premature infants: A network meta-analysis revealing the efficacy and safety.

BACKGROUND: Previous studies have neglected to report the specific action of different probiotic genera in preterm infants. To evaluate the efficacy and safety of specific probiotic genera, we performed a network meta-analysis (NMA) to identify the best prevention strategy for necrotizing enterocolitis in preterm infants. METHODS: MEDLINE, PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials had been searched for randomized control trials reporting the probiotics strategy for premature infants. RESULTS: We identified 34 eligible studies of 9161 participants. The intervention in the observation group was to add probiotics for feeding: Lactobacilli in 6 studies; Bifidobacterium in 8 studies; Bacillus in 1 study; Saccharomyces in 4 studies and probiotic mixture in 15 studies. This NMA showed a significant advantage of probiotic mixture and Bifidobacterium to prevent the incidence of necrotizing enterocolitis in preterm infants. A probiotic mixture showed effectiveness in reducing mortality in preterm infants. CONCLUSION: The recent literature has reported a total of 5 probiotic strategies, including Bacillus, Bifidobacterium, Lactobacillus, Saccharomyces, and probiotic mixture. Our thorough review and NMA provided a piece of available evidence to choose optimal probiotics prophylactic strategy for premature infants. The results indicated that probiotic mixture and Bifidobacterium showed a stronger advantage to use in preterm infants; the other probiotic genera failed to show an obvious effect to reduce the incidence of NEC, sepsis and all-cause death. More trials need to be performed to determine the optimal probiotic treatment strategy to prevent preterm related complications.

Transanal endorectal pull-through procedure versus transabdominal surgery for Hirschsprung disease: A systematic review and meta-analysis.

OBJECTIVE: To analyze the clinical results of transanal endorectal pull-through (TERPT) and transabdominal approach (TAB) in the treatment of Hirschsprung disease. METHODS: We searched all publications in the PubMed, MEDLINE, EMBASE, and Cochrane library databases between January 2003 and November 2018. The study included randomized controlled trials (RCTs) and observational clinical studies (OCSs), to compare the surgery duration, length of postoperative hospital stay, incidence of postoperative incontinence/soiling, constipation, and enterocolitis between the TERPT and TAB groups. Mantel-Haenszel method was used for continuous variables, the combined odds ratios (ORs) and 95% confidence intervals (CIs) for dichotomous variables were used. RESULTS: In the 87 studies, we include 1 case of RCTs and 9 cases of OCSs. Including 392 cases of TERPT and 332 cases of TAB groups. TERPT has a short postoperative hospitalization [mean difference (MD) = -6.74 day; 95% CIs; -13.26 to -0.23; P = .04], and a low incidence of postoperative incontinence (ORs = 0.54; 95% CIs, 0.35-0.83; P = .006) and constipation (ORs = 0.50; 95% CIs, 0.28-0.90; P = .02). There was no difference in duration of surgery (MD = -30.59 min; 95% CIs, -98.01-36.83; P = .37) and incidence of postoperative enterocolitis (ORs = 0.78; 95% CIs, 0.53-1.17; P = .23). CONCLUSION: TERPT is superior to TAB in terms of hospitalization time, postoperative incontinence, and constipation. However, there are still a large number of RCTs to verify, and more trials are expected to be testified in the future.

Probiotic strategies to prevent necrotizing enterocolitis in preterm infants: a meta-analysis.

PURPOSE: We aimed to compare probiotics with placebo for necrotizing enterocolitis in preterm infants and to evaluate the safety and effect and strict effect of specific probiotic genera. METHODS: Data recorded until January 2019 were searched, and relevant academic articles from PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were selected by two independent reviewers. Two reviewers independently included randomized controlled trials that compared probiotics and placebo in preterm infants. The outcomes included more than one of the following outcomes: incidence of necrotizing enterocolitis, necrotizing enterocolitis-related mortality, incidence of sepsis, and all-cause mortality. Two reviewers independently extracted data and assessed the risk of bias and quality of evidence. RESULTS: We identified 34 eligible studies of 9161 participants. This meta-analysis showed an overall advantage of probiotics to prevent the incidence of necrotizing enterocolitis (3.54%) and gut-associated sepsis (15.59%), and decrease mortality (5.23%) in preterm infants. A probiotic mixture showed a huge advantage and vitality in preventing necrotizing enterocolitis (2.48%) and gut-associated sepsis (18.39%), and in reducing mortality (5.57%) in preterm infants. CONCLUSION: The probiotic mixture showed advantages over the single strains to decrease the incidences of necrotizing enterocolitis and gut-associated sepsis, and mortality in preterm infants.

Comparison of conservative treatment with appendectomy for acute uncomplicated pediatric appendicitis: a meta-analysis.

Aim: We aimed to compare conservative treatment with surgery for uncomplicated pediatric appendicitis to estimate effectiveness and safety. Methods: Data recorded until September 2018 were searched, and relevant academic articles from PubMed, EMBASE, the Cochrane Library and other libraries were selected. STATA version 13.0 (Stata Corporation, TX, USA) was used for statistical analysis. Results: We identified nine eligible papers. The study reported a significant difference in the success rate of treatment in 1 month and in 1 year, and no difference in the incidence of complications. The patients with fecaliths showed low treatment efficacy in conservative treatment group (p < 0.05). Conclusion: Standardized conservative treatment as inpatients for pediatric appendicitis is safe and feasible. Appendectomy was the better choice for patients with fecaliths.

Association of neural tube defects with maternal alterations and genetic polymorphisms in one-carbon metabolic pathway.

BACKGROUND: Neural tube defects (NTDs) are birth defects of the brain, spine, or spinal cord invoked by the insufficient intake of folic acid in the early stages of pregnancy and have a complex etiology involving both genetic and environmental factors. So the study aimed to explore the association between alterations in maternal one-carbon metabolism and NTDs in the offspring. METHODS: We conducted a case-control study to get a deeper insight into this association, as well as into the role of genetic polymorphisms. Plasma concentrations of folate, homocysteine (Hcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and genotypes and alleles distributions of 52 SNPs in 8 genes were compared for 61 women with NTDs-affected offspring and 61 women with healthy ones. RESULTS: There were significant differences between groups with regard to plasma folate, SAM, SAH and SAM/SAH levels. Logistic regression results revealed a significant association between maternal plasma folate level and risk of NTDs in the offspring. For MTHFD1 rs2236225 polymorphism, mothers having GA genotype and A allele exhibited an increased risk of NTDs in the offspring (OR = 2.600, 95%CI: 1.227-5.529; OR = 1.847, 95%CI: 1.047-3.259). For MTHFR rs1801133 polymorphism, mothers having TT and CT genotypes were more likely to affect NTDs in the offspring (OR = 4.105, 95%CI: 1.271-13.258; OR = 3.333, 95%CI: 1.068-10.400). Moreover, mothers carrying T allele had a higher risk of NTDs in the offspring (OR = 1.798, 95%CI: 1.070-3.021). For MTRR rs1801394 polymorphism, the frequency of G allele was significantly higher in cases than in controls (OR = 1.763, 95%CI: 1.023-3.036). Mothers with NTDs-affected children had higher AG genotype in RFC1 rs1051226 polymorphism than controls, manifesting an increased risk for NTDs (OR = 3.923, 95%CI: 1.361-11.308). CONCLUSION: Folic acid deficiency, MTHFD1 rs2236225, MTHFR rs1801133, MTRR rs1801349 and RFC1 rs1051226 polymorphisms may be maternal risk factors of NTDs.

Association of neural tube defects with gene polymorphisms in one-carbon metabolic pathway.

PURPOSE: Neural tube defects (NTDs) are common congenital malformations. In this study, we aimed to explore the association between single nucleotide polymorphisms (SNPs) related to one-carbon metabolism (OCM) and NTDs in Han population of Northern China. METHODS: A case-control study was conducted in 152 children with NTDs and 169 controls. Twenty-nine SNPs in five genes were genotyped by Sequenom MassARRAY technology, and haplotype analysis was done by Haploview4.2 software. RESULTS: The allele frequency of rs3733890 in betaine-homocysteine methyltransferase (BHMT) gene was statistically different between NTDs and control groups (P = 0.041), and the children with A allele had higher risk for NTDs than G allele (OR = 1.408, 95%CI 1.013-1.956). In addition, there was a statistical difference in the allele and genotype frequencies of rs1051266 in reduced folate carrier1 (RFC1) gene between cases and controls (P = 0.013, 0.034), and the risk for NTDs was also higher in children with G allele and GG genotype, compared with A allele and AA genotype, respectively (OR = 1.492, 95%CI 1.089-2.044; OR = 2.020, 95%CI 1.081-3.780). The statistical significant difference was also found in allele frequency of rs1805087 in methionine synthetase (MTR) gene between cases and controls (P = 0.031), and the children with G allele were associated with an increased NTDs risk, compared with A allele (OR = 1.664, 95%CI 1.045-2.647). Meanwhile, haplotype analysis showed C-A-A-A haplotype of BHMT, and G-G-G-T haplotype of RFC1 was correlated with an increased risk of NTDs, but C-G-A-A haplotype of BHMT and G-G-C-A haplotype of MTR might decrease the risk of NTDs. CONCLUSIONS: The BHMT gene rs3733890, RFC1 gene rs1051266 and MTR gene rs1805087 were associated with the occurrence of NTDs in Han population of Northern China. It was confirmed that the gene variation related to OCM was one of the susceptibility factors for NTDs.

LY294002 induces differentiation and inhibits invasion of glioblastoma cells by targeting GSK-3beta and MMP.

Glioblastomas are the most common and devastating primary tumors of the central nervous system, with high proliferative capacity, aggressive invasion, and resistance to conventional therapies. Differentiation therapy has emerged as a promising candidate modality. Here we show that the traditional phosphatidylinositol 3 kinase (PI3K) inhibitor LY294002 is capable of inducing differentiation of C6 glioblastoma cells characterized by morphological changes to astrocytic phenotype, increase in differentiation marker protein glial fibrillary acidic protein and inhibition of proliferation. Small interfering RNA against glycogen synthase kinase-3ß (GSK-3ß) suppresses the induced-differentiation and invasiveness in C6 cells. LY294002 also inhibits MMP-9 expression and invasion of C6 cells, assembling the role of metalloprotease (MMP) inhibitor AG3340. Taken together, these findings suggest differentiation-inducing and invasion-inhibitory effectiveness of LY294002 in glioblastomas, most likely involving inhibition of GSK-3ß and MMP respectively.