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Objective: The aim of this work was to identify the consensus immune subtypes and predict the response to immune checkpoint inhibitor (ICIs) therapy for MDM4 gain/amplification luminal A type breast cancer (BC). Materials and Methods: Luminal A type BC expression data, copy number and corresponding clinical information were downloaded and pre-processed for subsequently analysis from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). Furthermore, gene set enrichment analysis (GSEA) was performed to identify transcripts functions between MDM4 gain/amplification and control samples. Subsequently, weighted gene co-expression network analysis (WGCNA) was applied to screen out gene modules related biomarkers for ICIs therapy response in luminal A type BC. We perform an unsupervised consensus clustering in MDM4 gain/amplification luminal A type BC from TCGA BC dataset based immune-related gene signatures (IRGs) and then used luminal A type BC from METABRIC BC as validation datasets. We performed the Tumor Immune Dysfunction and Exclusion (TIDE) analysis to predict ICIs response and explore significant relationship with immune subtype. Results: The results from GSEA indicated that luminal A type BC with MDM4 gain/amplification were significantly enriched in immunological signature gene sets. Significantly, we also identified three gene modules significantly association with immune checkpoint, DNA damage, and immune cell infiltering in luminal A type BC. Luminal A type BC could be categorized into two distinct immune subtypes based on the expression of IRGs. Luminal A type BC in one subtype showed high response to ICIs therapy, characterized by higher immune checkpoint genes score and CD8+ T-cell score compared to tumors in a second subtype. Conclusion: Our findings demonstrated that immune subtype for MDM4 gain/amplification luminal A type BC was beyond the current luminal A/B classification and a subset of luminal A type BC patients may benefit from ICIs therapy.

Background Clinical value of tumor necrosis factor (TNF) inhibitors in in vitro fertilization-embryo transfer (IVF-ET) in infertile women with polycystic ovary syndrome (PCOS) was investigated in this study. Methods A retrospective analysis was performed on the clinical data of 100 PCOS patients who received IVF-ET for the first time at Hebei Institute of reproductive health science and technology from January 2010 to June 2020. The patients were divided into Inhibitor group and Control group according to whether they were treated with or without TNF inhibitors. Next, the two groups were subject to comparison in terms of the days of gonadotropin (Gn) use, total dosage of Gn, trigger time, hormone level and endometrial condition on the day of human chorionic gonadotropin (HCG) injection, the effects of two different regimens on controlled ovarian hyperstimulation (COH) and pregnancy outcomes. Results There were no significant differences in baseline characteristics between the two groups, including age, duration of infertility, body mass index (BMI), ovarian volume, antral follicle count, and basal hormone levels. Compared with the Control group, the days of Gn use and trigger time of patients in the Inhibitor group were significantly shortened, and the total Gn dosage was notably reduced. In terms of sex hormone levels on the HCG injection, the Inhibitor group displayed much lower serum estradiol levels while higher serum luteinizing hormone and progesterone (P) levels than the Control group. Notably, the high-quality embryo rate was also significantly increased with the use of TNF inhibitors. However, significant differences were not observed in endometrial thickness (on the day of HCG injection), proportion of endometrial A, B and C morphology (on the day of HCG injection), cycle cancellation rate, number of oocytes retrieved, fertilization rate, and cleavage rate between the two groups. Importantly, the clinical pregnancy rate in the Inhibitor group was significantly higher than that in the Control group, but there was no significant difference in the biochemical pregnancy rate, early abortion rate, multiple birth rate, ectopic pregnancy rate and number of live births between the two groups. Conclusion Collectively, after application of TNF-α inhibitor regimen, superior overall treatment effect can be observed in infertile PCOS patients receiving IVF-ET. Therefore, TNF inhibitors have certain application value in IVF-ET in infertile women with PCOS.

The loss of N in farmland is an important cause of agricultural non-point source pollution, which seriously impacts the aquatic environment. A two-year (2017–2018) experiment was conducted to investigate the characteristics of runoff and N losses under different tillage practices. Taking downslope ridge planting and cross ridge planting as the experimental treatments, the characteristics of surface runoff, interflow, and N losses in sloping farmlands with yellow soil were studied throughout the maize growth period. As the rainfall increased, the surface runoff and interflow also increased. The surface runoff and N losses in the surface runoff of downslope ridge planting were significantly higher than those of cross ridge planting. The interflow volumes and N losses in the 0–20 and 20–40 cm soil layers of the cross ridge planting were significantly higher than those of the downslope ridge planting. The total N (TN) losses from surface runoff accounted for 54.95–81.25% of the N losses from all pathways. Therefore, we inferred that surface runoff is the main pathway of N losses. Dissolved total N (DTN) was the main form of N loss under different tillage measures, as it accounted for 55.82–94.41% of the TN losses, and dissolved organic N accounted for 52.81–87.06% of the DTN losses. Thus, we inferred that dissolved N is the main form of N loss. Future research must focus on the prevention and control of the N losses during the maize seedling stage to reduce the environmental pollution caused by ammonium N through runoff.

In the era of coronavirus disease 2019 (COVID-19) pandemic, imported COVID-19 cases pose great challenges to many countries. Chest CT examination is considered to be complementary to nucleic acid test for COVID-19 detection and diagnosis. We report the first community infected COVID-19 patient by an imported case in Beijing, which manifested as nodular lesions on chest CT imaging at the early stage. Deep Learning (DL)-based diagnostic systems quantitatively monitored the progress of pulmonary lesions in 6 days and timely made alert for suspected pneumonia, so that prompt medical isolation was taken. The patient was confirmed as COVID-19 case after nucleic acid test, for which the community transmission was prevented timely. The roles of DL-assisted diagnosis in helping radiologists screening suspected COVID cases were discussed.

Severe aplastic anemia (SAA) is a fatal bone marrow failure disease. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a matched sibling donor is the first-line treatment for older SAA patients. However, the number of CD34A 45-year-old male patient with SAA was treated with a sibling-matched allo-HSCT. Due to the low amount of donor CD34This study provides evidence that UCB-derived HSCs have a higher capacity for hematopoietic reconstitution, suggesting that UCB plus an HLA-matched sibling donor is a good alternative for older patients with SAA.

In this paper, a class of new extended shift-splitting (NESS) preconditioners containing t > 0 are proposed for saddle point problems, which contain the existing shift-splitting-based preconditioners as special cases. The convergence properties of the NESS iteration and the spectral distribution of the NESS preconditioned matrix are investigated. We give an estimated bound for the real eigenvalues of the NESS preconditioned matrix whose left end is positive and show that the non-real eigenvalues of the NESS preconditioned matrix are located in an intersection of two rings, particularly, these non-real eigenvalues are located in an intersection of two rings and one circle if t ≥ 1 2 . Moreover, we show that under appropriate conditions our proposed eigenvalue bounds are tighter than the corresponding bounds given in Ren et al. (2017). Using Fourier analysis, we derive an optimized parameter t ∗ independent of the viscosity ν for the continuous version of the NESS preconditioned GMRES method for the 2D Stokes equation. Moreover, we find that the NESS preconditioned GMRES method with a constant multiple of the optimized parameter t ∗ is effective and robust to solve 2D Stokes problems in practice. Numerical experiments are used to verify our theoretical results.

A stable and simple Yb:YAG rod amplifier based on chirped pulse amplification in a water cooling system has been demonstrated. The output power of 38 W at a 250 kHz repetition rate with a spectrum width of 4 nm centered at 1030 nm, which support Fourier-transform limited pulse duration of 389 fs has been generated. The compressed power of 23.9 W with pulse duration of 985 fs has been obtained with a chirped volume Bragg grating compressor. The power stability is measured to be 1.414% when the output power is 35 W. The system is worthwhile to popularize for its good performance and inexpensive cost.

Cotton, one of the most important crops in the world, produces natural fiber materials for the textile industry. WRKY transcription factors play important roles in plant development and stress responses. However, little is known about whether and how WRKY transcription factors regulate fiber development of cotton so far. In this study, we show that a fiber-preferential WRKY transcription factor, GhWRKY16, positively regulates fiber initiation and elongation. GhWRKY16-silenced transgenic cotton displayed a remarkably reduced number of fiber protrusions on the ovule and shorter fibers compared to the wild-type. During early fiber development, GhWRKY16 directly binds to the promoters of GhHOX3, GhMYB109, GhCesA6D-D11, and GhMYB25 to induce their expression, thereby promoting fiber initiation and elongation. Moreover, GhWRKY16 is phosphorylated by the mitogen-activated protein kinase GhMPK3-1 at residues T-130 and S-260. Phosphorylated GhWRKY16 directly activates the transcription of GhMYB25, GhHOX3, GhMYB109, and GhCesA6D-D11 for early fiber development. Thus, our data demonstrate that GhWRKY16 plays a crucial role in fiber initiation and elongation, and that GhWRKY16 phosphorylation by GhMPK3-1 is essential for the transcriptional activation on downstream genes during the fiber development of cotton.

Spatiotemporally regulated callose deposition is an essential, genetically programmed phenomenon that promotes pollen development and functionality. Severe male infertility is associated with deficient callose biosynthesis, highlighting the significance of intact callose deposition in male gametogenesis. The molecular mechanism that regulates the crucial role of callose in production of functional male gametophytes remains completely unexplored. Here, we provide evidence that the gradual upregulation of a previously uncharacterized cotton (Gossypium hirsutum) pollen-specific SKS-like protein (PSP231), specifically at the post pollen-mitosis stage, activates callose biosynthesis to promote pollen maturation. Aberrant PSP231 expression levels caused by either silencing or overexpression resulted in late pollen developmental abnormalities and male infertility phenotypes in a dose-dependent manner, highlighting the importance of fine-tuned PSP231 expression. Mechanistic analyses revealed that PSP231 plays a central role in triggering and fine-tuning the callose synthesis and deposition required for pollen development. Specifically, PSP231 protein sequesters the cellular pool of RNA-binding protein GhRBPL1 to destabilize GhWRKY15 mRNAs, turning off GhWRKY15-mediated transcriptional repression of GhCalS4/GhCalS8 and thus activating callose biosynthesis in pollen. This study showed that PSP231 is a key molecular switch that activates the molecular circuit controlling callose deposition toward pollen maturation and functionality and thereby safeguards agricultural crops against male infertility.

This study aimed to assess the overall diagnostic accuracy of magnetic beads-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MB-based MALDI-TOF MS) in identifying esophageal squamous cell carcinoma (ESCC). The PubMed/Medline, EMBASE, Cochrane Library, Science Direct, Google Scholar, China National Knowledge Infrastructure database and Wanfang Med Online were searched for potential studies up to 30 January 2018. Articles were screened manually on the basis of inclusion and exclusion criteria. Sensitivity, specificity, likelihood ratio or other indices reflecting the diagnostic accuracy of MB-based MALDI-TOF MS for ESCC were pooled and calculated. 16 studies involving 1 006 individuals were included. The values of pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were 0.95 (95% CI: 0.90–0.98), 0.94 (95% CI: 0.90–0.96), 15.45 (95% CI: 8.93–26.72), 0.05 (95% CI: 0.03–0.10), 295.04 (95% CI: 103.79–838.71), respectively. The area under the summary receiver operating characteristic (SROC) curve was 0.98. In conclusion, MB-based MALDI-TOF MS could be an effective technique with high diagnostic accuracy for ESCC. Keywords: Diagnostic value, ESCC, MALDI-TOF MS, Magnetic beads, Meta-analysis

BACKGROUND Papillary thyroid cancer (PTC) is currently the most commonly diagnosed endocrine malignancy. In addition, the sex- and age-adjusted incidence of PTC has exhibited a greater increase over the last 2 decades than in many other malignancies. Thus, discovering noninvasive specific serum biomarker to distinguish PTC from cancer-free controls in its early stages remains an important goal. MATERIAL AND METHODS Serum samples from 88 PTC patients and 80 cancer-free controls were randomly allocated into training or validation sets. Serum peptide profiling was performed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) after using weak cation exchange magnetic beads (WCX-MB), and the results were evaluated by use of ClinProTools™ Software. To distinguish PTC from cancer-free controls, quick classifier (QC), supervised neural network (SNN), and genetic algorithm (GA) models were established. The models were blindly validated to verify their diagnostic capabilities. The most discriminative peaks were subsequently identified with a nano-liquid chromatography-electrospray ionization-tandem mass spectrometry system. RESULTS Six peptide ions were identified as the most discriminative peaks between the PTC and cancer-free control samples. The QC model exhibited satisfactory sensitivity and specificity among the 3 models that were validated. Two peaks, at m/z 2671.17 and m/z 1464.68, were identified as fragments of the alpha chain of fibrinogen, while a peak at m/z 1738.92 was a fragment of complement component 4A/B. CONCLUSIONS MS combined with ClinProTools™ software was able to detect peptide biomarkers in PTC patients. In addition, the constructed classification models provided a serum peptidome pattern for distinguishing PTC from cancer-free controls. Both fibrinogen a and complement C4A/B were identified as potential markers for diagnosis of PTC.

Appropriate environmentally friendly agricultural technologies and practices must be implemented in China (and many other countries) to reduce farmland non-point source pollution and meet sustainability objectives. A major hindrance to their implementation is that Chinese farmers have very low willingness to accept such practices. Discrete choice experiments (DCEs) have known value for identifying goods or policies with attractive attributes, and thus exploring target groups’ choice behavior and addressing such problems. Sound questionnaire design is of paramount importance for robust results. This article describes the nature and theoretical foundations of DCEs and considers their use in diverse applications abroad, and their limited but growing applications in China. It then presents a case study, focused on the detailed design of DCEs intended to gauge paddy farmers’ willingness to accept several agriculturally friendly techniques and related compensation methods, problems encountered, and predictions for future studies.

TO THE EDITOR: In a subset of patients with acute promyelocytic leukemia (APL), t(15;17)(q22;q12) and PML - RARA fusion cannot be detected.[1][1][⇓][2]-[3][3] To date, many RARA fusions have been reported with at least 12 alternative partner genes in APL.[1][1],[4][4][⇓][5][⇓][6][⇓][7

Acute promyelocytic leukemia (APL) is a unique disease entity in acute myeloid leukemia (AML), characterized by the expansion of leukemic cell block at the promyelocytic stage. The vast majority of APL patients bear t(15;17)(q24;q21) involving the promyelocytic leukemia ( PML ) gene at chromosome

LIM domain proteins are cysteine-rich proteins, and are often considered as actin bundlers and transcription factors in plants. However, the roles of XLIM proteins in plants (especially in cotton) remain unexplored in detail so far. In this study, we identified a cotton XLIM protein (GhXLIM6) that is preferentially expressed in cotton fiber during whole elongation stage and early secondary cell wall (SCW) synthesis stage. The GhXLIM6-silenced transgenic cotton produces shorter fibers with thinner cell walls, compared with wild-type (WT). GhXLIM6 protein could directly bind F-actin and promote actin polymerization both in vitro and in vivo. It also acts as a transcription factor to suppress GhKNL1 expression through binding the PAL-box element of GhKNL1 promoter, and subsequently regulate the expression of CesA genes related to cellulose biosynthesis and deposition in SCWs of cotton fibers. The cellulose content in fibers of GhXLIM6RNAi cotton is lower than that in WT. Taken together, these data reveal the dual roles of GhXLIM6 in fiber development. On one hand, GhXLIM6 functions in fiber elongation through binding to F-actin to maintain the dynamic F-actin cytoskeleton. On the other hand, GhXLIM6 fine-tunes fiber SCW formation, probably through directly suppressing transcription of GhKNL1 to promote cellulose biosynthesis.

Polo-like kinase 1 (PLK1) is highly expressed in many cancers and therefore a biomarker of transformation and potential target for the development of cancer-specific small molecule drugs. RO3280 was recently identified as a novel PLK1 inhibitor, however its therapeutic effects in leukemia treatment are still unknown. We found that the PLK1 protein was highly expressed in leukemia cell lines as well as 73.3% (11/15) of pediatric acute myeloid leukemia (AML) samples. PLK1 mRNA expression was significantly higher in AML samples compared with control samples (82.95 ± 110.28 vs. 6.36 ± 6.35, p &lt, 0.001). Kaplan-Meier survival analysis revealed that shorter survival time correlated with high tumor PLK1 expression (p = 0.002). The 50% inhibitory concentration (IC50) of RO3280 for acute leukemia cells was between 74 and 797 nM. The IC50 of RO3280 in primary acute lymphocytic leukemia (ALL) and AML cells was between 35.49 and 110.76 nM and 52.80 and 147.50 nM, respectively. RO3280 induced apoptosis and cell cycle disorder in leukemia cells. RO3280 treatment regulated several apoptosis-associated genes. The regulation of DCC, CDKN1A, BTK, and SOCS2 was verified by western blot. These results provide insights into the potential use of RO3280 for AML therapy, however, the underlying mechanisms remain to be determined.

Background Overexpression of cyclin D1 dependent kinases 4 and 6 (CDK4/6) is a common feature of many human cancers including leukemia. LEE011 is a novel inhibitor of both CDK4 and 6. To date, the molecular function of LEE011 in leukemia remains unclear. Methods Leukemia cell growth and apoptosis following LEE011 treatment was assessed through CCK-8 and annexin V/propidium iodide staining assays. Cell senescence was assessed by β-galactosidase staining and p16INK4a expression analysis. Gene expression profiles of LEE011 treated HL-60 cells were investigated using an Arraystar Human LncRNA array. Gene ontology and KEGG pathway analysis were then used to analyze the differentially expressed genes from the cluster analysis. Results Our studies demonstrated that LEE011 inhibited proliferation of leukemia cells and could induce apoptosis. Hoechst 33,342 staining analysis showed DNA fragmentation and distortion of nuclear structures following LEE011 treatment. Cell cycle analysis showed LEE011 significantly induced cell cycle G1 arrest in seven of eight acute leukemia cells lines, the exception being THP-1 cells. β-Galactosidase staining analysis and p16INK4a expression analysis showed that LEE011 treatment can induce cell senescence of leukemia cells. LncRNA microarray analysis showed 2083 differentially expressed mRNAs and 3224 differentially expressed lncRNAs in LEE011-treated HL-60 cells compared with controls. Molecular function analysis showed that LEE011 induced senescence in leukemia cells partially through downregulation of the transcriptional expression of MYBL2. Conclusions We demonstrate for the first time that LEE011 treatment results in inhibition of cell proliferation and induction of G1 arrest and cellular senescence in leukemia cells. LncRNA microarray analysis showed differentially expressed mRNAs and lncRNAs in LEE011-treated HL-60 cells and we demonstrated that LEE011 induces cellular senescence partially through downregulation of the expression of MYBL2. These results may open new lines of investigation regarding the molecular mechanism of LEE011 induced cellular senescence. Electronic supplementary material The online version of this article (doi:10.1186/s12935-017-0405-y) contains supplementary material, which is available to authorized users.

It has been reported that suppression of selenium‑binding protein 1 (SBP1) occurs in many human malignancies which is considered to play an important role in cancer development and progression. Despite its importance in cancer, the function and factors that regulate its expression are not known. Using cell proliferation assays, immunochemical staining and immunoblotting and flow cytometry methods and in a xenograft model, we evaluated the role of SBP1 in proliferation, migration, senescence and chemoresistance of gastric cancer cells (SGC7901 and BGC823) to cisplatin. It was noted that diminished SBP1 expression increased gastric cancer cell proliferation and cell migration and decreased cisplatin-induced apoptosis while its overexpression produced the opposite effects. These results suggest that SBP1 plays a significant role in gastric cancer cell proliferation and modulates its response to anticancer drugs. These results suggest that SBP1 can serve as a potential target to suppress gastric cancer.

Purpose The aims of this study were to determine whether the changes in density and location of CD68-positive and CD206-positive macrophages contribute to progression of hepatocellular carcinoma (HCC) and to evaluate prognostic values of these cells in post-surgical patients. Methods A retrospective study involving 268 HCC patients was conducted. CD68-positive and CD206-positive macrophage infiltration in HCC tissues and adjacent tissues was examined by immunohistochemistry (IHC) and the relationship between clinicopathologic features and prognosis was analyzed. Receiver operating characteristics (ROC) curve was used to calculate diagnostic accuracy. Results There was an increase in CD68-positive and CD206-positive macrophage infiltrations in adjacent tumor tissues compared with tumor tissues. ROC curve identified their optimal diagnostic cutoff values. The survival analysis showed that increased CD68 expression in adjacent tissues conferred superior overall survival (OS) and disease-free survival (DFS), while increase of CD206 in tumor yielded inferior OS and DFS. Cox regression analysis suggested both CD68-positive macrophages in adjacent area and intratumor CD206-positive macrophages as independent prognostic biomarkers for post-surgical HCC patients. Finally, a combination of CD68/CD206 and HBV-positive further improved prognostic stratification, especially in DFS. These results provide the first evidence for region- and subset-dependent involvement of CD68 and CD206 cells in HCC progression. A combination of CD68/CD206 density and HBV-positivity improves further predictive value for post-operative recurrence of HCC. Conclusion Quantification of CD68/CD206 macrophages and their distribution can be exploited for better postsurgical management of HCC patients. These findings provide a basis for developing novel treatment strategies aimed at re-educating macrophages in tumor microenvironment.

Aims Although cognitive dysfunction is a common neurological complication in elderly patients with diabetes, the mechanisms underlying this relationship remain unclear, and effective preventive interventions have yet to be developed. Thus, this study investigated the preventive effects and mechanisms of action associated with granulocyte colony-stimulating factor (G-CSF) on cognitive dysfunction in elderly diabetic mice with cerebral small vessel disease. Methods This study included 40 male db/db diabetic and wild-type (WT) mice that were categorized into the following four groups at the age of 3 weeks: db/db group (DG), db/db+G-CSF group (DGG), WT group (WG), and WT+G-CSF group (WGG). The mice were fed normal diets for 4 months and then given G-CSF (75 μg/kg) via intraperitoneal injections for 1 month. At 7.5 months of age, the cognitive abilities of the mice were assessed with the Y-maze test and the Social Choice Test; body weight, blood pressure (BP), and blood glucose measurements were obtained throughout the study. Brain imaging and blood oxygen level-dependent (BOLD) contrast imaging analyses were performed with a small animal magnetic resonance imaging (MRI) system, autophagosome levels were detected with a transmission electron microscope (TEM), hippocampal neurons were assessed with hematoxylin and eosin (HE) staining, and protein expressions and distributions were evaluated using immunohistochemistry and Western blot analyses. Results (i) The body weight and blood glucose levels of the DG and DGG mice were significantly higher than those of the WG and WGG mice; (ii) social choice and spatial memory capabilities were significantly reduced in DG mice but were recovered by G-CSF in DGG mice; (iii) the MRI scans revealed multiple lacunar lesions and apparent hippocampal atrophy in the brains of DG mice, but G-CSF reduced the number of lacunar lesions and ameliorated hippocampal atrophy; (iv) the MRI-BOLD scans showed a downward trend in whole-brain activity and reductions in the connectivities of the hippocampus and amygdala with subcortical structures in DG mice, but G-CSF clearly improved the altered brain activity as well as the connectivity of the hippocampus in DGG mice; (v) HE staining revealed fewer neurons in the hippocampus in DG mice; (vi) TEM analyses revealed significantly fewer autophagosomes in the hippocampi of DG mice, but G-CSF did not increase these numbers; (vii) there were significant reductions in mechanistic target of rapamycin (mTOR) and LC3-phosphatidylethanolamine conjugate (LC3)-II/I levels in the hippocampi of DG mice, whereas p62 was upregulated, and G-CSF significantly enhanced the levels of Beclin1, mTOR, and LC-II/I in DGG mice; and (viii) G-CSF significantly reversed increases in nuclear factor κB (NF-κB) protein levels in DG but not in WG mice. Conclusions In this study, aged diabetic mice were prone to cognitive dysfunction and cerebral small vessel disease. However, administration of G-CSF significantly improved cognitive function in elderly db/db diabetic mice, and this change was likely related to the regulation of autophagy and NF-κB signaling pathways.

Multilingual abstracts in the six official working languages of the United Nations. (PDF 402Â kb)

Objective: To investigate the relationship between growth patterns and mandibular posterior tooth-alveolar bone complex morphology in a Chinese population with normal occlusion. Methods: Forty-five patients with normal occlusion (23 males, 22 females) were included in this study. Among these patients, 20 displayed the vertical growth pattern, and 20 had the horizontal growth pattern, while the remaining patients displayed the average growth pattern. All of the patients underwent dental cone beam computed tomography (CBCT), which included the region of the mandibular posterior teeth and the alveolar. A linear regression analysis and a correlation analysis between the facial height index (FHI) and the alveolar bone morphology were performed. Results: The inclination of the molars, the thickness of the cortical bone, and the height of the mandibular bone differed significantly between patients with the horizontal growth pattern and those with the vertical growth pattern (P

Background Acute myeloid leukemia (AML) is the second-most common form of leukemia in children. Aberrant DNA methylation patterns are a characteristic feature of AML. GATA4 has been suggested to be a tumor suppressor gene regulated by promoter hypermethylation in various types of human cancers although the expression and promoter methylation of GATA4 in pediatric AML is still unclear. Methods Transcriptional expression levels of GATA4 were evaluated by semi-quantitative and real-time PCR. Methylation status was investigated by methylation-specific PCR (MSP) and bisulfate genomic sequencing (BGS). The prognostic significance of GATA4 expression and promoter methylation was assessed in 105 cases of Chinese pediatric acute myeloid leukemia patients with clinical follow-up records. Results MSP and BGS analysis showed that the GATA4 gene promoter is hypermethylated in AML cells, such as the HL-60 and MV4-11 human myeloid leukemia cell lines. 5-Aza treatment significantly upregulated GATA4 expression in HL-60 and MV4-11 cells. Aberrant methylation of GATA4 was observed in 15.0 % (3/20) of the normal bone marrow control samples compared to 56.2 % (59/105) of the pediatric AML samples. GATA4 transcript levels were significantly decreased in AML patients (33.06 ± 70.94; P = 0.011) compared to normal bone marrow/idiopathic thrombocytopenic purpura controls (116.76 ± 105.39). GATA4 promoter methylation was correlated with patient leukocyte counts (WBC, white blood cells) (P = 0.035) and minimal residual disease MRD (P = 0.031). Kaplan-Meier survival analysis revealed significantly shorter overall survival time in patients with GATA4 promoter methylation (P = 0.014). Conclusions Epigenetic inactivation of GATA4 by promoter hypermethylation was observed in both AML cell lines and pediatric AML samples; our study implicates GATA4 as a putative tumor suppressor gene in pediatric AML. In addition, our findings imply that GATA4 promoter methylation is correlated with WBC and MRD. Kaplan-Meier survival analysis revealed significantly shorter overall survival in pediatric AML with GATA4 promoter methylation but multivariate analysis shows that it is not an independent factor. However, further research focusing on the mechanism of GATA4 in pediatric leukemia is required. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1760-5) contains supplementary material, which is available to authorized users.

Long non-coding RNA (lncRNA) plays a role in gene transcription, protein expression and epigenetic regulation; and altered expression results in cancer development. Acute myeloid leukemia (AML) is rare in children; and thus, this study profiled lncRNA expression in bone marrow samples from pediatric AML patients. Arraystar Human LncRNA Array V3.0 was used to profile differentially expressed lncRNAs in three bone marrow samples obtained from each pediatric AML patient and normal controls. Quantitative polymerase chain reaction (qRT-PCR) was performed to confirm dysregulated lncRNA expressions in 22 AML bone marrow samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to construct the lncRNA-mRNA co-expression network. A total of 372 dysregulated lncRNAs (difference ≥10-fold) were found in pediatric AML patients compared to normal controls. Fifty-one mRNA levels were significantly upregulated, while 85 mRNA levels were significantly downregulated by >10-fold in pediatric AML, compared to normal controls. GO terms and KEGG pathway annotation data revealed that cell cycle pathway-related genes were significantly associated with pediatric AML. As confirmed by qRT-PCR, expression of 24 of 97 lncRNA was altered in pediatric AML compared to normal controls. In pediatric AML, ENST00000435695 was the most upregulated lncRNA, while ENST00000415964 was the most downregulated lncRNA. Data from this study revealed dysregulated lncRNAs and mRNAs in pediatric AML versus normal controls that could form gene pathways to regulate cell cycle progression and immunoresponse. Further studies are required to determine whether these lncRNAs could serve as novel therapeutic targets and bbdiagnostic biomarkers in pediatric AML.

Background Wilms’ tumor (WT) is one of the most common malignant neoplasms of the urinary tract in children. Anaplastic histology (unfavorable histology) accounts for about 10% of whole WTs, and it is the single most important histologic predictor of treatment response and survival in patients with WT; however, until now the molecular basis of this phenotype is not very clearly. Methods A real-time polymerase chain reaction (PCR) array was designed and tested. Next, the gene expression profile of pediatric anaplastic histology WT and normal adjacent tissues were analyzed. These expression data were anlyzed with Multi Experiment View (MEV) cluster software further. Datasets representing genes with altered expression profiles derived from cluster analyses were imported into the Ingenuity Pathway Analysis Tool (IPA). Results 88 real-time PCR primer pairs for quantitative gene expression analysis of key genes involved in pediatric anaplastic histology WT were designed and tested. The gene expression profile of pediatric anaplastic histology WT is significantly different from adjacent normal controls; we identified 15 genes that are up-regulated and 16 genes that are down-regulated in the former. To investigate biological interactions of these differently regulated genes, datasets representing genes with altered expression profiles were imported into the IPA for further analysis, which revealed three significant networks: Cancer, Hematological Disease, and Gene Expression, which included 27 focus molecules and a significance score of 43. The IPA analysis also grouped the differentially expressed genes into biological mechanisms related to Cell Death and Survival 1.15E−12, Cellular Development 2.84E−11, Cellular Growth and Proliferation 2.84E-11, Gene Expression 4.43E−10, and DNA Replication, Recombination, and Repair 1.39E−07. The important upstream regulators of pediatric anaplastic histology WT were TP53 and TGFβ1 signaling (P = 1.15E−14 and 3.79E−13, respectively). Conclusions Our study demonstrates that the gene expression profile of pediatric anaplastic histology WT is significantly different from adjacent normal tissues with real-time PCR array. We identified some genes that are dysregulated in pediatric anaplastic histology WT for the first time, such as HDAC7, and IPA analysis showed the most important pathways for pediatric anaplastic histology WT are TP53 and TGFβ1 signaling. This work may provide new clues into the molecular mechanisms behind pediatric anaplastic histology WT. Electronic supplementary material The online version of this article (doi:10.1186/s12935-015-0197-x) contains supplementary material, which is available to authorized users.

Acute myeloid leukemia (AML) is the second-most common form of leukemia in children. Aberrant DNA methylation patterns are characteristic of AML. Zinc finger protein 382 (ZNF382) has been suggested to be a tumor suppressor gene possibly regulated by promoter hypermethylation in various types of human cancer. However, ZNF382 expression and methylation status in pediatric AML is unknown. In the present study, ZNF382 transcription levels were evaluated by quantitative reverse-transcription PCR. Methylation status was investigated by methylation-specific (MSP) PCR and bisulfate genomic sequencing (BGS). The prognostic significance of ZNF382 expression and promoter methylation was assessed in 105 cases of pediatric AML. The array data suggested that the ZNF382 promoter was hypermethylated in the AML cases examined. MSP PCR and BGS analysis revealed that ZNF382 was hypermethylated in leukemia cell lines. Furthermore, treatment with 5-aza-2'-deoxycytidine (5-Aza) upregulated ZNF382 expression in the selected leukemia cell lines. The aberrant methylation of ZNF382 was observed in 10% (2/20) of the control samples compared with 26.7% (28/105) of the AML samples. ZNF382 expression was significantly decreased in the 105 AML patients compared with the controls. Patients with ZNF382 methylation showed lower ZNF382 transcript levels compared with patients exhibiting no methylation. There were no significant differences in clinical characteristics or cytogenetic analysis between the patients with or without ZNF382 methylation. ZNF382 methylation correlated with minimal residual disease (MRD). Kaplan-Meier survival analysis revealed similar survival times in the samples with ZNF382 methylation, and multivariate analysis revealed that ZNF382 methylation was not an independent prognostic factor in pediatric AML. The epigenetic inactivation of ZNF382 by promoter hypermethylation can be observed in AML cell lines and pediatric AML samples. Therefore, our study suggests that ZNF382 may be considered a putative tumor suppressor gene in pediatric AML. However, further studies focusing on the mechanisms responsible for ZNF382 downregulation in pediatric leukemia are required.

Background: Acute myeloid leukemia (AML) is the second most common form of leukemia in children. Aberrant DNA methylation patterns are a characteristic feature in various tumors, including AML. Metallothionein III (MT3) is a tumor suppresser reported to show promoter hypermethylated in various cancers. However, the expression and molecular function of MT3 in pediatric AML is unclear. Methods: Eleven human leukemia cell lines and 41 pediatric AML samples and 20 NBM/ITP (Norma bone marrow/ Idiopathic thrombocytopenic purpura) control samples were analyzed. Transcription levels of MT3 were evaluated by semi-quantitative and real-time PCR. MT3 methylation status was determined by methylation specific PCR (MSP) and bisulfite genomic sequencing (BSG). The molecular mechanism of MT3 was investigated by apoptosis assays and PCR array analysis. Results: The MT3 promoter was hypermethylated in leukemia cell lines. More CpG’s methylated of MT3 was observed 39.0% pediatric AML samples compared to 10.0% NBM controls. Transcription of MT3 was also significantly decreased in AML samples compared to NBM/ITP controls (P< 0.001); patients with methylated MT3 exhibited lower levels of MT3 expression compared to those with unmethylated MT3 (P = 0.049). After transfection with MT3 lentivirus, proliferation was significantly inhibited in AML cells in a dose-dependent manner (P< 0.05). Annexin V assay showed that apoptosis was significantly upregulated MT3-overexpressing AML cells compared to controls. Real-time PCR array analysis revealed 34 dysregulated genes that may be implicated in MT3 overexpression and apoptosis in AML, including FOXO1. Conclusion: MT3 may be a putative tumor suppressor gene in pediatric AML. Epigenetic inactivation of MT3 via promoter hypermethylation was observed in both AML cell lines and pediatric AML samples. Overexpression of MT3 may inhibit proliferation and induce apoptosis in AML cells. FOXO1 was dysregulated in MT3-overexpressing cells, offering an insight into the mechanism of MT3-induced apoptosis. However, further research is required to determine the underlying molecular details.

Objectives To provide toxicokinetic and clinical evidence of the hydrolytic effect of paraoxonase-1 (PON1) on acute organophosphate poisoning in rats. Methods 40 male Wistar rats were randomised into four equal groups. Dichlorvos administration group (A group) underwent dichlorvos injection (dissolved in corn oil) using intraperitoneal (ip) dose of 10 mg/kg. PON1 pretreatment group (B group) was injected with PON1 in the tail vein (intravenous), dose 9600 U/kg, 30 min prior to dichlorvos administration. In the treatment group (C group), atropine 0.05 mg/kg and pyraloxime chloride (PAM-CI) 120 mg/kg were injected intravenously within 2 min after dichlorvos administration. Finally, in the co-treatment group (D group), PON1 was injected intravenously with a dose of 9000 U/kg 30 min prior to dichlorvos administration; atropine 0.05 mg/kg and PAM-CI 120 mg/kg were injected intravenously within 2 min after dichlorvos administration. Blood was collected after administration. Plasma dichlorvos concentration was detected by liquid chromatography-mass spectra (LC-MS) method and clinical signs were observed. Toxicokinetic parameters were calculated in a statistical moment model. Results AUC (0→∞) in group B was statistically different from that in groups A and C (p0.05); there was no statistical difference between group A and group C (p>0.05). The statistical results of Cmax were the same as those of AUC (0→∞). There were no differences of MRT between four groups (p>0.05). Clinical signs can be improved by PON1 and atropine + PAM-CI, and co-treatment can relieve signs more effectively. Conclusion PON1 can decrease the amount of dichlorvos that entered the blood, lowered the peak concentration and relieved clinical signs.

Mitogen-activated protein kinase (MAPK) cascades play pivotal roles in mediating biotic and abiotic stress responses. Cotton (Gossypium hirsutum) is the most important textile crop in the world, and often encounters abiotic stress during its growth seasons. In this study, a gene encoding a mitogen-activated protein kinase (MAPK) was isolated from cotton, and designated as GhMPK17. The open reading frame (ORF) of GhMPK17 gene is 1494 bp in length and encodes a protein with 497 amino acids. Quantitative RT-PCR analysis indicated that GhMPK17 expression was up-regulated in cotton under NaCl, mannitol and ABA treatments. The transgenic Arabidopsis plants expressing GhMPK17 gene showed higher seed germination, root elongation and cotyledon greening/expansion rates than those of the wild type on MS medium containing NaCl, mannitol and exogenous ABA, suggesting that overexpression of GhMPK17 in Arabidopsis increased plant ABA-insensitivity, and enhanced plant tolerance to salt and osmotic stresses. Furthermore, overexpression of GhMPK17 in Arabidopsis reduced H2O2 level and altered expression of ABA- and abiotic stress-related genes in the transgenic plants. Collectively, these data suggested that GhMPK17 gene may be involved in plant response to high salinity and osmotic stresses and ABA signaling.

BACKGROUND: Iodiated contrast‐induced nephropathy (CIN) is a serious complication of contrast‐enhanced imaging. The aim of this study was to evaluate the diagnostic sensitivities and specificities of serum cystatin C (sCys C) and serum creatinine (sCr) for CIN and to further investigate difference of the incidence, risk factors, and in‐hospital and 3‐month prognosis of CIN according to sCys C criteria and sCr criteria. METHODS: We prospectively evaluated 213 patients who underwent angiography. The sCr and sCys C concentrations were detected before and at 48 hours, 72 hours after the procedure. The incidence, risk factors, and in‐hospital and 3‐month prognosis of CIN were analyzed. Receiver operating characteristic curve (ROC) analysis was performed for sCr and sCys C 48 hours after procedure. RESULTS: The incidence of CIN was 24.4% (sCys C criteria) and 8% (sCr criteria). Diabetes mellitus, dehydration, and hypoalbuminemia were independent risk factors for CIN. Area under the ROC of sCys C 48 hours after procedure was not superior to sCr (0.715 vs 0.790, P=.178). The mortality of patients with CIN in sCr criteria increased significantly (P

Objective: The purpose of this study was to evaluate three-dimensional (3D) dehiscence of upper anterior alveolar bone during incisor retraction and intrusion in adult patients with maximum anchorage. Methods: Twenty adult patients with bimaxillary dentoalveolar protrusion had the four first premolars extracted. Miniscrews were placed to provide maximum anchorage for upper incisor retraction and intrusion. A computed tomography (CT) scan was performed after placement of the miniscrews and treatment. The 3D reconstructions of pre- and post-CT data were used to assess the dehiscence of upper anterior alveolar bone. Results: The amounts of upper incisor retraction at the edge and apex were (7.64±1.68) and (3.91±2.10) mm, respectively, and (1.34±0.74) mm of upper central incisor intrusion. Upper alveolar bone height losses at labial alveolar ridge crest (LAC) and palatal alveolar ridge crest (PAC) were 0.543 and 2.612 mm, respectively, and the percentages were (6.49±3.54)% and (27.42±9.77)%, respectively. The shape deformations of LAC-labial cortex bending point (LBP) and PAC-palatal cortex bending point (PBP) were (15.37±5.20)° and (6.43±3.27)°, respectively. Conclusions: Thus, for adult patients with bimaxillary protrusion, mechanobiological response of anterior alveolus should be taken into account during incisor retraction and intrusion. Pursuit of maximum anchorage might lead to upper anterior alveolar bone loss.

A filamentous actinomycete, designated strain CCNWNQ 0016T, was isolated from soil from a zinc and copper mine in Shaanxi province, north-western China. A polyphasic taxonomic study was carried out to establish the status of strain CCNWNQ 0016T. Chemical and morphological properties of the isolate were similar to those of species of the genus Streptomyces. Analysis of the almost complete 16S rRNA gene sequence placed strain CCNWNQ 0016T in the genus Streptomyces where it formed a distinct phyletic line with recognized species of this genus. The strain exhibited highest sequence similarities to Streptomyces niveoruber NBRC 15428T (98.8 %), Streptomyces griseoviridis NBRC 12874T (98.7 %) and Streptomyces aurantiogriseus NBRC 12842T (98.7 %). Furthermore, DNA–DNA hybridization studies between the novel isolate and these three strains showed relatedness values of 49.6±0.6, 47.2±0.9 and 46.9±1.1 %, respectively. A number of phenotypic properties also enabled the isolate to be differentiated from related species of the genus Streptomyces. Therefore, it is proposed that strain CCNWNQ 0016T (=K42T =ACCC 41871T =HAMBI 3107T) should be classified as the type strain of a novel species in the genus Streptomyces, Streptomyces zinciresistens sp. nov. The maximum level of resistance to Zn2+ for strain CCNWNQ 0016T is 35 mM.