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Necrotizing enterocolitis (NEC) is a multifactorial gastrointestinal disease with high morbidity and mortality among premature infants. This study aimed to identify novel methylation-regulated biomarkers in NEC intestinal tissue through multiomics analysis. We analyzed DNA methylation and transcriptome datasets from ileum and colon tissues of patients with NEC. We identify methylation-related differential genes (MrDEGs) based on the rule that the degree of methylation in the promoter region is inversely proportional to RNA transcription. These MrDEGs included ADAP1, GUCA2A, BCL2L14, FUT3, MISP, USH1C, ITGA3, UNC93A and IL22RA1. Single-cell data revealed that MrDEGs were mainly located in the intestinal epithelial part of intestinal tissue. These MrDEGs were verified through Target gene bisulfite sequencing and RT-qPCR. We successfully identified and verified the ADAP1, GUCA2A, IL22RA1 and MISP, primarily expressed in intestinal epithelial villus cells through single-cell data. Through single-gene gene set enrichment analysis, we found that these genes participate mainly in the pathological process of T-cell differentiation and the suppression of intestinal inflammation in NEC. This study enhances our understanding of the pathogenesis of NEC and may promote the development of new precision medicine methods for NEC prediction and diagnosis. [ABSTRACT FROM AUTHOR]

Ferroptosis is a novel form of programmed cell death characterized by iron accumulation, lipid peroxidation, and a decline in antioxidant capacity, all of which are regulated by gene expression. The onset of numerous diseases is closely associated with ferroptosis. Common diseases affect a large population, reduce the quality of life, and impose an increased burden on the healthcare system. The role of ferroptosis in common diseases, its therapeutic potential, and even its translation into clinical drug treatments are currently significant research topics worldwide. This study preliminarily explores the theoretical basis of ferroptosis, its mechanism and treatment prospect in common diseases including ischaemia-reperfusion injury, inflammatory bowel diseases, liver fibrosis, acute kidney injury, diabetic kidney disease, stroke, Alzheimer's disease, cardiovascular disease, immune and cancer. This review provides a theoretical foundation for the further study and development of ferroptosis, as well as for the prevention and treatment of common diseases. [ABSTRACT FROM AUTHOR]

Objective: The identification of risk factors is crucial for the clinical prevention and diagnosis of necrotizing enterocolitis (NEC). Monochorionic twins (MCT), due to the high genetic homogeneity, provided a valuable model for investigating the risk factors of various diseases. This study aimed to explore the risk factors for NEC using MCT. Methods: A retrospective review was conducted on the medical records of monochorionic twins (MCT) treated at Guangzhou Women and Children's Medical Center from January 2012 to March 2023. We compared perinatal condition, feeding and preceding condition between MCT pairs with NEC (NEC MCT) and without NEC(No NEC MCT).Logistic regression analysis was utilized to identify independent risk factors. Result: In 85 pairs of monochorionic twins (MCT), NEC occurred in one twin in 78.8% of cases, whereas both twins were affected in 21.2% of cases. In the final cohort of 60 pairs of MCT, several parameters were found to differ significantly between NEC MCT group and No NEC MCT group. Compared to No NEC MCT group, the incidence of umbilical cord abnormalities was significantly higher in the NEC MCT group (25% vs. 8.3%, P = 0.014). Meanwhile, NEC MCT group showed higher prevalence of SGA infants (48.3% vs. 21.7%, P = 0.002) and sFGR (38.3% vs. 6.7%, P = 0.000). Furthermore, TTTs (13.3% vs. 3.3%, P = 0.027) and septicemia (25% vs. 5%, P = 0.002) were more common in NEC MCT group. In a multivariable logistic regression model, sFGR (OR 6.81,95%CI 2.1–21.9, p = 0.001) was eventually output as an independent risk factor. Conclusion: Non-genetic factors play a predominant role in the pathogenesis of NEC. Umbilical cord abnormalities, SGA, sFGR, TTTs and septicemia significantly increase the risk of NEC. sFGR is an independent risk factor of NEC. [ABSTRACT FROM AUTHOR]

Titanosilicate with H2O2 stands out as a highly consequential oxidized catalytic system, prized for its user‐friendly operation, mild conditions, and eco‐friendly attributes. However, a synthesis strategy for large surface area titanosilicalites approaching the theoretical lowest Si/Ti ratio without extra‐framework Ti species remains an ongoing challenge. In this study, we successfully synthesized single‐crystalline Ti‐rich nanosized aggregated TS‐1 by shielding effect with a Si/Ti polymer. This polymer demonstrated effectiveness in restraining TiO2 species by regulating the proximity of Si/Ti species in Ti‐Diol‐Si polymers. The polymer not only facilitated the synthesis of single‐crystalline Ti‐rich TS‐1 but also exploited the chain length of PEG, functioning as a shielding cage by hydrogen bonds, to synthesize nanosized aggregated TS‐1 (TS‐1‐PEG400). This TS‐1‐PEG400 exhibited superior conversion (~60%), selectivity (~90%), and stability in 1‐hexene epoxidation. This study not only establishes a synthesis pathway for Ti‐rich TS‐1 but also holds the potential to enhance related industrial oxidation reactions involving titanosilicates and H2O2. [ABSTRACT FROM AUTHOR]

Objectives: To develop a mediastinal shift angle (MSA) measurement method applicable to right-sided congenital diaphragmatic hernia (RCDH) in fetal MRI and to validate the predictive value of MSA in RCDH. Methods: Twenty-seven fetuses with isolated RCDH and 53 controls were included in our study. MSA was measured on MRI axial image at the level of four-chamber view of the fetal heart. The angle between the sagittal midline landmark line and the left boundary landmark line touching tangentially the lateral wall of the left ventricle was used to quantify MSA for RCDH. Appropriate statistical analyses were performed to determine whether MSA can be regarded as a valid predictive tool for postnatal outcomes. Furthermore, predictive performance of MSA was compared with that of lung area to head circumference ratio (LHR), observed/expected LHR (O/E LHR), total fetal lung volume (TFLV), and observed/expected TFLV (O/E TFLV). Results: MSA was significantly higher in the RCDH group than in the control group. MSA, LHR, O/E LHR, TFLV, and O/E TFLV were all correlated with postnatal survival, pulmonary hypertension (PH), and extracorporeal membrane oxygenation (ECMO) therapy (p < 0.05). Value of the AUC demonstrated good predictive performance of MSA for postnatal survival (0.901, 95%CI: (0.781–1.000)), PH (0.828, 95%CI: (0.661–0.994)), and ECMO therapy (0.813, 95%CI: (0.645–0.980)), which was similar to O/E TFLV but slightly better than TFLV, O/E LHR, and LHR. Conclusions: We developed a measurement method of MSA for RCDH for the first time and demonstrated that MSA could be used to predict postnatal survival, PH, and ECMO therapy in RCDH. Clinical relevance statement: Newly developed MRI assessment method of fetal MSA in RCDH offers a simple and effective risk stratification tool for patients with RCDH. Key Points: • We developed a measurement method of mediastinal shift angle for right-sided congenital diaphragmatic hernia for the first time and demonstrated its feasibility and reproducibility. • Mediastinal shift angle can predict more prognostic information other than survival in right-sided congenital diaphragmatic hernia with good performance. • Mediastinal shift angle can be used as a simple and effective risk stratification tool in right-sided congenital diaphragmatic hernia to improve planning of postnatal management. [ABSTRACT FROM AUTHOR]

Background: It has been demonstrated that circularRNA (circRNAs) plays a critical role in various cancers. While the potential molecular mechanism of circRNAs in the progression of colorectal cancer (CRC) remains uncertain. Methods: Differentially expressed circRNAs were identified by RNA sequencing. RT-qPCR detected the expression of circ_0009092, miR-665, and NLK in CRC tissues and cells. Functions of circ_0009092 on tumor cell proliferation, migration, and invasion were investigated by a series of in vitro assays. The underlying mechanism of circ_0009092 was explored by bioinformatics analysis, RNA immunoprecipitation (RIP) and luciferase assays. A co-culture assay in vitro was performed to detect the affection of circ_0009092 on macrophage recruitment in the tumor microenvironment (TME). A xenograft mouse model was used to explore the effect of circ_0009092 on tumor growth. Results: Circ_0009092 was downregulated in CRCand predicted a good prognosis. Overexpression of circ_0009092 reduced tumor cell EMT, proliferation, migration, and invasion in vitro and in vivo. Mechanistically, circ_0009092 elevated the NLK expression via sponging miR-665 and suppressed the Wnt/β-catenin signaling pathway. EIF4EA3 induced circ_0009092 expression in CRC cells. In addition, NLK regulates phosphorylation and O-GlcNAcylation of STAT3 by binding to STAT3, thereby inhibiting CCL2 expression, in which it inhibits macrophage recruitment in the tumor microenvironment (TME). Conclusion: EIF4A3 suppressed circ_0009092 biogenesis, whichinhibits CRC progression by sponging miR-665 to downregulate NLK. Circ_0009092/miR-665/NLK suppressed tumor EMT, proliferation, migration, and invasion by acting on the Wnt/β-catenin signaling pathway. NLK directly interacted with STAT3 and decreased the CCL2 expression, inhibiting the recruitment of tumor-associated macrophages (TAMs) in the TME. Our study provided novel insights into the roles of circ_0009092 as a novel promising prognostic and therapeutic target in CRC. [ABSTRACT FROM AUTHOR]

Introduction: Hirschsprung's disease (HSCR) is a developmental defect of the enteric nervous system (ENS), which is caused by abnormal development of enteric neural crest cells. Its occurrence is caused by genetic factors and environmental factors. It has been reported that single nucleotide polymorphisms (SNPs) of proprotein convertase subtilisin/kexin type 2 (PCSK2) gene are associated with HSCR. However, the correlation of HSCR in southern Chinese population is still unclear. Methods: We assessed the association of rs16998727 with HSCR susceptibility in southern Chinese children using TaqMan SNP genotyping analysis of 2943 samples, including 1470 HSCR patients and 1473 controls. The association test between rs16998727 and phenotypes was performed using multivariable logistic regression analysis. Results: We got an unexpected result, PCSK2 SNP rs16998727 was not significantly different from HSCR and its HSCR subtypes: S-HSCR (OR = 1.08, 95% IC: 0.93~1.27, P_adj = 0.3208), L-HSCR (OR = 1.07, 95% IC: 0.84~1.36, P_adj = 0.5958) and TCA (OR = 0.94, 95% IC: 0.61~1.47, P_adj = 0.8001). Conclusion: In summary, we report that rs16998727 (PCSK2 and OTOR) is not associated with the risk of HSCR in southern Chinese population. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the predictive value of mediastinal shift angle (MSA) in congenital diaphragmatic hernia (CDH). Methods: A retrospective analysis was performed on 87 fetuses with prenatally diagnosed left-sided CDH (LCDH) and 88 controls. MSA was measured on magnetic resonance imaging (MRI). Lung area to head circumference ratio (LHR), ratio of the observed/expected LHR (O/E LHR), total fetal lung volume (TFLV), and observed/expected total fetal lung volume (O/E TFLV) were also measured. Correlation of MSA with pulmonary hypertension (PH), extracorporeal membrane oxygenation (ECMO) use, duration of hospitalization and survival in neonates with CDH was analyzed. Performance of MSA in prediction of postnatal outcomes was compared with LHR, O/E LHR, TFLV, and O/E TFLV. Results: There were significant differences in MSA values not only between the CDH group and the control group but also in CDH patients with different survival outcomes. MSA was inversely correlated with O/E LHR, O/E TFLV, and TFLV. MSA, LHR, O/E LHR, TFLV, and O/E TFLV could all be used to predict survival of CDH patients. In addition, the receiver operating characteristic (ROC) curve showed that the test performance of MSA was similar to that of TFLV, O/E TFLV, and O/E LHR, but superior to that of LHR. MSA was also correlated with PH, need for ECMO support, and duration of hospitalization. Conclusion: MRI measurement of MSA can provide various prognostic information for prenatally diagnosed LCDH, in addition to postnatal survival. The test performance of MSA is similar to TFLV, O/E TFLV, and O/E LHR. Key Points: • Mediastinal shift angle (MSA) can be measured quickly and reproducibly on MRI images. • MSA could provide more prognostic information other than postnatal survival for LCDH with good test performance. • MSA should be incorporated into prenatal risk stratification for LCDH to improve planning of postnatal management. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer (BCa) is one of the most prevalent malignancies globally. Previous study has reported the inhibitory effect of methyltransferase-like 14 (METTL14) on BCa tumorigenesis, but its role in the cell migration, invasion and epithelial–mesenchymal transition (EMT) in BCa remains unknown. Materials and methods: Quantitative real-time PCR (RT-qPCR) and western blot were applied to measure RNA and protein expression respectively. Cell migration, invasion and EMT were evaluated by wound healing, Transwell, and immunofluorescence (IF) assays as well as western blot of EMT-related proteins. In vivo experiments were performed to analyze metastasis of BCa. Mechanism investigation was also conducted to study METTL14-mediated regulation of BCa progression. Results: METTL14 overexpression prohibits BCa cell migration, invasion in vitro and tumor metastasis in vivo. METTL14 stabilizes USP38 mRNA by inducing N6-methyladenosine (m6A) modification and enhances USP38 mRNA stability in YTHDF2-dependent manner. METTL14 represses BCa cell migration, invasion and EMT via USP38. Additionally, miR-3165 inhibits METTL14 expression to promote BCa progression. Conclusions: Our study demonstrated that METTL14 suppresses BCa progression and forms a feedback loop with USP38. In addition, miR-3165 down-regulates METTL14 expression to promote BCa progression. The findings may provide novel insight into the underlying mechanism of METTL14 in BCa progression. Author summary: Bladder cancer (BCa) is a common type of cancer that begins in the cells of the bladder and poses a significant threat to human health worldwide. In order to improve the diagnosis and treatment of BCa, molecular mechanisms associated with BCa tumorigenesis and tumor progression needs to be clarified. Currently, long non-coding RNAs (lncRNAs) have been suggested to act as regulators of cancer progression. Here, we identified lncRNA methyltransferase-like 14 (METTL14) as a tumor-suppressor gene in BCa, acting to inhibit cell migration, invasion and epithelial–mesenchymal transition (EMT) as well as tumor metastasis. We also found that METTL14 forms a feedback loop with ubiquitin specific peptidase 38 (USP38) in BCa. In addition, microRNA-3165 (miR-3165) was verified as an upstream regulator of METTL14 and was elucidated to downregulate METTL14 expression, contributing to the malignancy of BCa. Given that the therapeutic potential of some miRNAs have been identified in a number of diseases, targeting miR-3165 may be a potential therapeutic strategy in BCa treatment. Our study provides new insights into the understanding of molecular mechanism by which METTL14 regulates BCa progression and offer novel and potential targets for BCa treatment. [ABSTRACT FROM AUTHOR]

Background: Tumor budding (TB) is emerging as a prognostic factor in multiple cancers. Likewise, the stemness of cancer cells also plays a vital role in cancer progression. However, nearly no research has focused on the interaction of TB and tumor stemness in cancer. Methods: Tissue microarrays including 229 cases of invasive breast cancer (BC) were established and subjected to pan-cytokeratin immunohistochemical staining to evaluate molecular expression. Univariate and multivariate analyses were applied to identify prognostic factors of BC, and the Chi-square test was used for comparison of categorical variables. Results: High-grade TB was significantly associated with T stage, lymph node metastasis, tumor node metastasis (TNM) stage, epithelial-mesenchymal transition, and poor disease-free survival (DFS) of BC patients. We also found that the prognostic value of TB varied widely among different subtypes and subgroups. Cox regression analysis then showed that TB grade was an independent prognostic factor. Moreover, cancer stem cell (CSC) markers CD44 and ALDH1A1 were significantly higher in high-grade TB tumors. Consequently, patients were classified into high CSC score subgroup and low CSC score subgroups. Further research found that CSC scores correlated with clinicopathological features and DFS of BC patients. Based on TB grade and CSC scores, we classified BC patients into TBlow-CSCslow (type I), TBlow-CSCshigh (type II), TBhigh-CSCslow (type III), and TBhigh-CSCshigh (type IV) subgroups. Survival analysis showed that patients in the type I subgroup had the best DFS, whereas those in the type IV subgroup had the worst DFS. Finally, a TB-CSC-based nomogram for use in BC was established. The nomogram was well calibrated to predict the probability of 5-year DFS, and the C-index was 0.837. Finally, the area under the curve value for the nomogram (0.892) was higher than that of the TNM staging system (0.713). Conclusion: The combination of TB grade with CSC score improves the prognostic evaluation of BC patients. A novel nomogram containing TB grade and CSC score provides doctors with a candidate tool to guide the individualized treatment of cancer patients. [ABSTRACT FROM AUTHOR]

Endoscopy for revealing the orifice of congenital H‐type tracheoesophageal fistula (cTEF) is important for diagnostics and therapeutics. To facilitate the identification and catheterization of cTEF, we developed a new modified flexible endoscopy technique using a laryngeal mask with intermittent airflow. A retrospective case series study was conducted from April 2016 to July 2019 at a national regional children's medical center. Twelve infants with cTEF underwent this flexible endoscopy technique. The intermittent positive pressure airflow through laryngeal mask was able to reveal the orifice of cTEF easily in tracheal lumen. Under the visual flexible endoscope, cannulation with a 3‐Fr ureteral catheter in fistula was successfully used in all cases. There were no immediate or delayed complications. This case series shows that the flexible endoscopy technique is a safe, easy, and technically efficient approach for diagnosis and cannulation of cTEF. [ABSTRACT FROM AUTHOR]

Collecting duct carcinoma (CDC) is a rare and highly aggressive subtype of kidney cancer that is associated with a poor prognosis. At present, there is no effective treatment for CDC. Herein, we report a case of metastatic CDC treated with a combination of a tyrosine kinase inhibitor and an immune checkpoint inhibitor. A 67-year-old male was diagnosed with CDC with lung and bone metastasis. Pazopanib and camrelizumab were administered after cytoreductive nephrectomy. The patient achieved a partial response after one cycle of treatment; however, he then experienced serious drug-induced hepatic injury. Therefore, we discontinued camrelizumab and administered monotherapy with pazopanib. Three months later, the cancer had progressed and axitinib and sintilimab were administered. The patient achieved a partial response, accompanied by the complete disappearance of the metastatic lesion in the lung. The patient had an excellent physical status after 11 months. This is the first reported case of metastatic CDC successfully treated with a combination of a tyrosine kinase inhibitor and an immune checkpoint inhibitor. This form of combination treatment may be an effective option for treating metastatic CDC. [ABSTRACT FROM AUTHOR]

Aim: To explore the association between miR-938rs2505901 T>C polymorphism and Hirschsprung disease (HSCR) risk in Chinese children. Materials & Methods: We conducted a case–control study in a Chinese population with 1381 cases and 1457 controls. The associated correlation strengths were assessed by adjusted odds ratios (AORs) and 95% CIs. Results: The results revealed that the rs2505901 TC and rs2505901 TC/CC genotype were related to an increased HSCR risk compared to the risk contributed by the rs2505901 TT genotype. A stratification analysis showed that the rs2505901 TC/CC genotype promoted the progression of HSCR more significantly in patients with the short-segment HSCR subtype. Conclusion: Our study indicated that miR-938rs2505901 T>C polymorphism is significantly associated with HSCR risk in Chinese children. This result needs to be confirmed with well-designed studies. Hirschsprung disease (HSCR) is the most common intestinal disorder in infants. Genetic defects play important roles in the occurrence and development of HSCR. This case–control study was performed by collecting data from 1381 cases and 1457 controls to evaluate the association between the miR-938rs2505901 T>C genetic defect and HSCR risk. The results showed that allele rs2505901 C may be a risk factor. The rs2505901 TC or rs2505901 TC/CC genotype was related to an increased HSCR risk compared to the risk contributed by the rs2505901 TT genotype. An expression quantitative trait locus (eQTL) analysis indicated that allele rs2505901 C is linked with high levels of miR-938. Our study may provide a target and a valuable reference for the clinical treatment, classification and prognosis of HSCR. [ABSTRACT FROM AUTHOR]

Introduction: Hirschsprung disease (HSCR), characterized by the defective migration of enteric neural crest cells, is a severe congenital tract disease in infants. Its etiology is not clear at present, although a genetic component plays an important role in its etiology. Many studies focused on the polymorphisms of microRNA (miRNA) in several disease progressions have been reported, including HSCR. However, the findings remain inconclusive. The present study aimed to explore the association of genetic variants in miRNAs and HSCR susceptibility in Southern Chinese children. Methods: Five single nucleotide polymorphisms (SNPs) (miR‐146A rs2910164, miR‐4318 rs8096901, miR‐3142 rs2431697, miR‐3142 rs2431097 and miR‐3142 rs5705329) were included to be genotyped in the stratified analysis through the Mass ARRAY iPLEX Gold system (Sequenom, San Diego, CA, USA) conducted on all the samples, comprising 1470 cases and 1473 controls. After quality control, the minor allele frequency was compared in cases and controls to analyze the association between SNPs and HSCR using PLINK 1.9 (https://www.cog‐genomics.org/plink) and multiple heritability models were tested (additive, recessive and dominant models). Results: Our results indicated that miR‐4318 rs8096901 polymorphisms were associated with HSCR susceptibility in Southern Chinese children, especially in short‐segment HSCR (S‐HSCR) patients after stratified analysis. Conclusions: In summary, we report that miR‐4318 rs8096901 was associated with HSCR, especially in SHSCR patients. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study is to assess the value of saline-aided ultrasound (US) in diagnosing congenital duodenal obstruction (CDO). Methods: The neonates with CDO were enrolled in this study, including the neonates confirmed with annular pancreas (AP) by operation, the neonates confirmed with duodenal atresia, the neonates confirmed with duodenum web, and the neonates confirmed with malrotation. Pertinent data were recorded, including the US features, intraoperative findings, and surgical procedures. The methodology of this study is a diagnostic test study which means the US feature is the test and the intraoperative finding is the gold standard. Results: A total of 95 neonates were enrolled, including 33 neonates with AP, 6 neonates with duodenal atresia, 29 neonates with duodenum web, and 27 neonates with malrotation. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the hyperechogenic band for the detection of AP were 78.8% (26/33), 90.3% (56/62), 81.2% (26/32), 88.8% (56/63), and 86.3% (82/95), respectively. The sensitivity, specificity, NPV, and accuracy for the detection of duodenal atresia were 0% (0/6), 100% (89/89), 93.6% (89/95), and 93.6% (89/95), respectively. The sensitivity, specificity, PPV, NPV, and accuracy for the detection of duodenum web were 100% (29/29), 100% (66/66), 100% (29/29), 100% (66/66), and 100% (95/95), respectively. The sensitivity, specificity, PPV, NPV, and accuracy for the detection of malrotation were 100% (27/27), 100% (68/68), 100% (27/27), 100% (68/68), and 100% (95/95), respectively. Conclusion: Saline-aided US is a feasible tool to diagnose CDO. [ABSTRACT FROM AUTHOR]

Background: Hirschsprung disease (HSCR) is a rare congenital gastrointestinal disease characterized by the absence of intestinal submucosal and myometrial ganglion cells. Recently, researches indicated that miR-100 regulated the growth, differentiation and apoptosis of neurons, and affected the functions of HSCR-associated pathways. While miR-100 rs1834306 A>G polymorphism was shown to modify the susceptibility to tumors, the association between this polymorphism and HSCR susceptibility is still unknown. Methods: This was a case–control study consisting of 1470 HSCR cases and 1473 controls from southern China. DNA was genotyped by TaqMan real-time PCR. Odds ratios (ORs) and 95% confidence intervals (CIs) were used as statistical indicators. Results: We found that miR-100 rs1834306 G allele and GG genotype significantly increased HSCR susceptibility (GG vs AA: adjusted OR=1.31, 95% CI=1.04– 1.64, P=0.020; G vs A: adjusted OR=1.12, 95% CI=1.01– 1.25, P=0.041; GG vs AA/AG: adjusted OR=1.30, 95% CI=1.07– 1.59, P=0.010). In the stratified analysis, miR-100 rs1834306 GG genotype carriers had higher risk to develop HSCR in all clinical subtypes when compared with those with AA/AG genotypes, and OR was rising with HSCR aggravation (SHSCR: adjusted OR=1.28, 95% CI=1.03– 1.59, P=0.029; LHSCR: adjusted OR=1.48, 95% CI=1.06– 2.07, P=0.020; TCA: adjusted OR=2.12, 95% CI=1.22– 3.69, P=0.008). Conclusion: Our findings suggested that miR-100 rs1834306 A>G polymorphism was associated with increased HSCR susceptibility in southern Chinese children. Furthermore, miR-100 rs1834306 GG genotype had a greater genetic pathopoiesis in severe HSCR. [ABSTRACT FROM AUTHOR]

Background: Hirschsprung disease (HSCR) is a congenital disease that arises from defective intestinal neural system. LncRNA HOTTIP is a critical gene in various diseases, including HSCR. No epidemiological studies have explored the correlation between lncRNA HOTTIP single nucleotide polymorphisms (SNPs) and HSCR risk. We here lead as a pioneer to explore whether SNPs in lncRNA HOTTIP impact the risk of HSCR and HSCR subtypes in an unrelated Chinese population. Methods: We used the TaqMan method to genotype rs3807598 C>G of the lncRNA HOTTIP gene using 1470 HSCR cases and 1473 healthy controls. Of them, 1441 cases and 1434 controls were successfully genotyped. We adopted odds ratios (ORs) and 95% confidence intervals (CIs) to quantify the relationship. Results: We got an unexpected outcome that lncRNA HOTTIP SNP rs3807598 C>G could not modify the risk of HSCR (CG vs. CC: adjusted OR=0.89, 95% CI=0.74– 1.07; GG vs. CC: adjusted OR=1.10, 95% CI=0.89– 1.37; GG/CG vs CC: adjusted OR=0.95, 95% CI=0.80– 1.13; and GG vs. CC/CG: adjusted OR=1.19, 95% CI=0.99– 1.43). What's more, risk effect of lncRNA HOTTIP rs3807598 C>G is still not obvious in stratification analysis by HSCR subtype. Conclusion: Our studies did not provide statistical evidence of a correlation between lncRNA HOTTIP SNP rs3807598 C>G and susceptibility of HSCR in the Chinese population that is being studied. Further validation study with a larger sample size covering multi-ethnic groups is warranted. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the ability of upper gastrointestinal (GI) saline-contrast ultrasound (US) to detect neonatal annular pancreas.Methods: Sixty-two neonates, who presented duodenal obstruction and were examined by upper GI saline-contrast US before treatment, were retrospectively analyzed and categorized into four groups according to their final diagnosis: group A, annular pancreas (n = 28); group B, duodenal atresia (n = 2); group C, descending duodenal septum (n = 25); and group D, normal (n = 7). The ultrasonic characteristics were analyzed that especially focused on whether the angle between the prestenotic and poststenotic descending duodenum (at or below a derived cutoff) could identify neonatal annular pancreas.Results: To detect annular pancreas using the concave contour of the distal prestenotic duodenum, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined at 71.4%, 100%, 100%, and 80.9%, respectively. When using the hyperechogenic band around the constricted duodenum, the sensitivity, specificity, PPV, and NPV were determined at 82.1%, 94.1%, 92%, and 86.5%, respectively. For using the 40.7° acute angle cutoff between prestenotic and poststenotic descending duodenum, the values of sensitivity, specificity, PPV, and NPV were determined at 100%, 97.1%, 96.6%, and 100%, respectively, of which the area under the receiver operating characteristic curve was 0.979.Conclusions: Upper GI saline-contrast US has a lower possibility for misdiagnosis of neonatal annular pancreas when considering the acute angle between the prestenotic and poststenotic descending duodenum.Key Points: • This study includes the largest series of neonates with annular pancreas of which the characteristics were analyzed using the upper GI saline-contrast US. • Neonatal annular pancreas may be diagnosed by the characteristics-concave contour of the distal prestenotic duodenum; acute angle cutoff of 40.7° between the prestenotic and poststenotic duodenum; the "S" shape formed by the pylorus, the duodenal bulb, and the prestenotic and poststenotic descending duodenum. • The acute angle with the highest diagnostic value can be used to quantitatively diagnose neonatal annular pancreas and avoid potential misdiagnosis caused by sonographers' subjectivity. [ABSTRACT FROM AUTHOR]

There is an important relationship between gradient of pressure and the bootstrap current. Due to the α (a gradient scale of pressure) is the essential condition to trap discrete Alfvén eigenmodes (α-induced Alfvén eigenmodes, namely αTAEs), here, we focus on the relationship between αTAEs and bootstrap current with a magnetohydrodynamic (MHD) simulation code and a gyrokinetic-MHD hybrid simulation code in two typical scenarios in ITER, and compare these typical scenarios with two ordinary scenarios about physical characteristics of discrete Alfvén eigenmodes. These discrete Alfvén eigenmodes are always lying in the region of high bootstrap current. However, they are not corresponding absolutely in pure radio frequency scenario (one of typical scenarios) because of large-α. Moreover, we illustrate the multiple branches of discrete Alfvén eigenmodes in those typical scenarios, and find high-order modes trapped by the lower potential well. Discrete Alfvén eigenmodes exist widely in ITER scenarios with bootstrap current. However, discrete Alfvén eigenmodes are quasi-marginally stable in MHD description and could be readily destabilized by energetic particles in hybrid simulation via wave-particle resonances. [ABSTRACT FROM AUTHOR]

Background: Platelet-derived growth factor receptor alpha (PDGFRα) is a cell-surface receptor tyrosine kinase for platelet-derived growth factors. Correct timing and level of Pdgfra expression is crucial for embryo development, and deletion of Pdgfra caused developmental defects of multiple endoderm and mesoderm derived structures, resulting in a complex phenotypes including orofacial cleft, spina bifida, rib deformities, and omphalocele in mice. However, it is not clear if deletion of Pdgfra at different embryonic stages differentially affects these structures. Purpose: To address the temporal requirement of Pdgfra in embryonic development. Methods: We have deleted the Pdgfra in Pdgfra-expressing tissues at different embryonic stages in mice, examined and quantified the developmental anomalies. Results: Current study showed that (i) conditional deletion of Pdgfra at different embryonic days (between E7.5 and E10.5) resulted in orofacial cleft, spina bifida, rib cage deformities, and omphalocele, and (ii) the day of Pdgfra deletion influenced the combinations, incidence and severities of these anomalies. Deletion of Pdgfra caused apoptosis of Pdgfra-expressing tissues, and developmental defects of their derivatives. Conclusion: Orofacial cleft, spina bifida and omphalocele are among the commonest skeletal and abdominal wall defects of newborns, but their genetic etiologies are largely unknown. The remarkable resemblance of our conditional Pdgfra knockout embryos to theses human congenital anomalies, suggesting that dysregulated PDGFRA expression could cause these anomalies in human. Future work should aim at defining (a) the regulatory elements for the expression of the human PDGFRA during embryonic development, and (b) if mutations / sequence variations of these regulatory elements cause these anomalies. [ABSTRACT FROM AUTHOR]

Purpose: The prognostic value of serum cystatin-C (Cys-C) in renal cell carcinoma (RCC) remains unknown. The purpose of this study is to explore the prognostic value of Cys-C for RCC patients. Patients and methods: The levels of preoperative Cys-C, creatinine (CRE) and estimated glomerular filtration rate (e-GFR) were retrospectively collected in 325 RCC patients undergoing surgery. The cutoff values of Cys-C, CRE and e-GFR were determined by the standardized Cutoff Finder algorithm. The receiver operating characteristic (ROC) curve and pairwise comparison were performed to compare the three variables. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic value of serum Cys-C in RCC. Results: Based on the analysis of Cutoff Finder algorithm, ROC curve and pairwise comparison, the preoperative Cys-C was superior to CRE and e-GFR as a predictive factor in RCC. Multivariate Cox regression analyses showed that high preoperative Cys-C (>1.09 mg/L) was significantly associated with shorter overall survival (OS) in all RCC patients (hazard ratio [HR], 1.59; P = 0.012), patients at pT1-2 (P<0.001), pN0 (P<0.001) and pM0 stages (P<0.001). Moreover, Multivariate Cox regression analyses also showed that in the 306 patients without metastasis, high preoperative Cys-C was also associated with shorter disease-free survival (DFS) (HR, 3.50; P = 0.013). Conclusions: An elevated preoperative Cys-C level was demonstrated to be related with worse survival in patients with RCC. Measuring preoperative serum Cys-C might be a simple way for finding poor prognostic patients and patients with elevated preoperative Cys-C level should be more closely followed up. [ABSTRACT FROM AUTHOR]

IFN-γ is generally believed to be important in the autoimmune pathogenesis of type 1 diabetes ( T1 D). However, the development of spontaneous β-cell autoimmunity is unaffected in NOD mice lacking expression of IFN-γ or the IFN-γ receptor ( IFNγ R), bringing into question the role IFN-γ has in T1 D. In the current study, an adoptive transfer model was employed to define the contribution of IFN-γ in CD4+ versus CD8+ T cell-mediated β-cell autoimmunity. NOD. scid mice lacking expression of the IFNγ R β chain ( NOD. scid. IFNγ RBnull) developed diabetes following transfer of β cell-specific CD8+ T cells alone. In contrast, β cell-specific CD4+ T cells alone failed to induce diabetes despite significant infiltration of the islets in NOD. scid. IFNγ RBnull recipients. The lack of pathogenicity of CD4+ T-cell effectors was due to the resistance of IFNγ R-deficient β cells to inflammatory cytokine-induced cell death. On the other hand, CD4+ T cells indirectly promoted β-cell destruction by providing help to CD8+ T cells in NOD. scid. IFNγ RBnull recipients. These results demonstrate that IFN-γ R may play a key role in CD4+ T cell-mediated β-cell destruction. [ABSTRACT FROM AUTHOR]

Background: Hirschsprung disease (HSCR, aganglionic megacolon) is the most frequent genetic cause of congenital intestinal obstruction. DSCAM was identified as associated to HSCR with Down Syndrome (DS-HSCR) in European population,but failed to replicate in the non-syndromic HSCR patients. We aim to further investigate the relationship of DSCAM with non-sydromic HSCR in a South Chinese cohort, the largest case-control study so far. Method: We analyzed 1394 HSCR patients and 973 healthy controls. Two polymorphisms (rs2837770 A > G, rs8134673 A > G) on DSCAM were genotyped using Sequenom Massarray platform. Results: Both SNPs were confirmed as associated with non-syndromic HSCR in the South Chinese population ( P = 1.69E-03, OR = 1.29 for SNP rs2837770 and P = 3.00E-03, OR = 1.27 for SNP rs8134637). Of note, we demonstrated the associated SNPs were more likely to affect a subgroup of patients with short-segment aganglionosis (S-HSCR) ( P = 3.06E-03,OR = 1.21 for SNP rs2837770 and P = 3.33E-03,OR = 1.21 for SNP rs8134637). Conclusion: There is an association between DSCAM polymorphisms and non-syndromic HSCR in South Chinese population. [ABSTRACT FROM AUTHOR]