Comprehension of Ditransitive Constructions in Mandarin-Speaking Children with Developmental Language Disorder and Children with Autism Spectrum Disorder Plus Language Impairment.

This study examined and compared the comprehension of Mandarin ditransitive constructions in children with developmental language disorder (DLD) and children with autism spectrum disorder plus language impairment (ALI). Eighteen children with DLD, 17 children with ALI, and 27 age-matched typically developing (TDA) children, participated in a sentence-picture matching task on four patterns of Mandarin ditransitive constructions. Both children with DLD and children with ALI received significantly lower accuracy than TDA children in general and their most common errors were thematic role reversals. However, while children with ALI evinced a generalized deficit in all four patterns, only the comprehension of S1 (Subj. + Vgei + IO + DO) and S3 (Subj. + gei + IO + V + DO) was affected in children with DLD, with that of S2 (Subj. + V + DO + gei + IO) and S4 (Subj. + V + IO + DO) preserved in this population. Additionally, thematic role reversal errors were more dominant in children with DLD than in children with ALI who also committed a relatively higher proportion of Wrong Theme and No Recipient errors. It is concluded that the primary deficit of children with DLD lies in representing dependent relationships between the arguments and the verb as involved in thematic role assignment, but this is less critical in children with ALI, with their performance on the comprehension task possibly also related to other factors associated with the condition. To enhance the development of ditransitive constructions, intervention efforts for children with DLD and children with ALI could focus on strengthening the connection between each argument and its thematic role.

Clinicopathological and predictive significance of SIRT1 and peroxisome proliferator-activated receptor gamma in esophageal squamous cell carcinoma: The correlation with EGFR and Survivin.

SIRT1 (silent mating type information regulation 2 homolog 1) is an enzyme that deacetylates proteins that contributes to cell survival and angiogenesis. Peroxisome proliferator-activated receptor Ƴ (PPAR Ƴ) is a member of the nuclear steroid hormone receptor superfamily and regulates cell apoptosis and proliferation. The functional roles of SIRT1 and PPAR Ƴ in tumor progression remain controversy. This study aims to investigate the roles of SIRT1 and PPAR Ƴ in esophageal squamous cell carcinoma (ESCC), as well as correlation with expression of EGFR and Survivin. Here, we analyzed the protein expression of SIRT1 and PPAR Ƴ in tumor microarray with ESCC and its associations with clinicopathological parameters and overall survival. Both SIRT1 and PPAR Ƴ were highly expressed in tumor tissues comparing with non-cancerous epithelium. High expression of SIRT1 was positively correlated with advanced TNM stage and poor outcome, while high expression of PPAR Ƴ was positively related with tumor grading, not with patients' prognosis. In addition, the high expression of SIRT1 was positively correlated with overexpression of EGFR, not related with PPAR Ƴ or Survivin expression status. These data suggests SIRT1 may serve as a predictor of poor prognosis in ESCC, and its mediated tumor-promoting role might be associated with the overexpression of EGFR protein in ESCC.

The expression and clinical relevance of PD-1, PD-L1, and TP63 in patients with diffuse large B-cell lymphoma.

Latest study showed that a novel translocation between programmed cell death ligand 1 (PD-L1) (cluster of differentiation 274) and TP63 (tumor protein 63) can be found in diffuse large B-cell lymphoma (DLBCL), resulting in their conjunct overexpression in tumor cells at RNA level. However, the expressed pattern of these 2 genes at protein level in DLBCL remains largely unknown, and the clinical relevance of PD-L1 and TP63 expression in DLBCL are also unclear.Tumor tissues from 76 Chinese DLBCL patients were immunostained for programmed cell death 1 (PD-1), PD-L1, and TP63 using the EnVision system. Clinical relevance of PD-1, PD-L1, and TP63 in 74 DLBCL were analyzed by chi-square test, the Kaplan-Meier curves with log rank test, and Cox's proportional hazards regression model.PD-1 was mainly expressed in tumor-infiltrating lymphocytes (TILs) of 39.5% patients. PD-L1 was expressed in tumor cells of 26.3% patients, and TP63 was immunostained in nucleoli of tumor cells of 31.6% cases. PD-1 expression was significantly associated with the patients' gender and B symptoms (P = 0.032, P = 0.026). DLBCL with PD-L1 or TP63 expression in tumor cells showed low International Prognostic Index (IPI) score (P = 0.007, P = 0.009). PD-1 TILs was related to prolonged overall survival rate (OS) of DLBCL patients (P = 0.02), whereas PD-L1 expression was associated with worse clinical outcome of patients (P = 0.049). Immunoreactivity of TP63 was not correlated with patients' survival time. Besides, PD-1 expression, patients' age, Ann Arbor stage, and IPI score were significant prognostic markers for OS, but PD-L1 and TP63 had no prognostic significance.PD-1, PD-L1, and TP63 are frequently expressed in DLBCL. PD-1/PD-L1/TP63 blockade may be a potential therapeutic strategy for some patients.

Lower expression of platelet derived growth factor is associated with better overall survival rate of patients with idiopathic nonspecific interstitial pneumonia.

BACKGROUND: Idiopathic nonspecific interstitial pneumonia (INSIP) presents with varying degrees of interstitial inflammation and fibrosis exhibiting a uniform appearance. Lack of knowledge on the underlying mechanisms of INSIP has contributed to few effective treatment strategies. Our study is designed to explore aberrantly expressed cytokines involvement in INSIP development. METHODS: Oligo GEArray was employed to detect the expression of cytokines in INSIP patients, and idiopathic pulmonary fibrosis (IPF) was setup as isotype control. Real-time PCR and immunohistochemistry analysis were used to further confirm the expression of abnormally expressed cytokines. The correlationship between cytokines expression and overall survival rate of patients with IPF and INSIP were analyzed. RESULTS: From microarray detection, transforming growth factor-beta-1 (TGF-ß1), fibroblast growth factor 10 (FGF10), and platelet derived growth factor (PDGF) were predominantly up-regulated in patients with INSIP. Real-time PCR and immunohistochemistry also showed these cytokines was abnormally expressed in INSIP. In addition to, the clinical relevance analysis demonstrated relatively lower expression of PDGF patients had longer overall survival rate than those with higher expression of PDGF. CONCLUSIONS: Our study suggests that TGF-ß1, FGF10, and PDGF are required for the pathogenesis of INSIP, and may therefore be ideal targets in INSIP treatment. Moreover, INSIP patients with lower expression of PDGF had better survival rate.

TRAF6 promotes the invasion and metastasis and predicts a poor prognosis in gastric cancer.

PURPOSE: This study investigated the relationships of TRAF6 expression with clinical pathologic parameters and the prognosis of patients with gastric cancer. This study also explored the roles of TRAF6 in cell apoptosis and invasiveness, as well as underlying molecular mechanism of gastric cancer cell line in vitro. METHODS: A total of 90 cases of tissue microarrays were immunohistochemically analyzed for TRAF6 expression. Cell proliferation was measured by MTT assay. Flow cytometry was used for analyzing cell apoptosis and cell invasion ability was detected by a Transwell invasion assay. Protein expression was assessed by Western blotting. RESULTS: TRAF6 was expressed in 53 of 90 (58.9%) cases of gastric cancer. TRAF6 expression was significantly positively correlated with advanced N stage, pathological stage and a poor prognosis, but not an independent predictor of a poor prognosis in gastric cancer (p=0.083). The knockdown of TRAF6 increased cell apoptosis and reduced invasive ability of BGC-823 cell. Moreover, TRAF6 down-regulation decreased protein levels of phosphor-Akt, Bcl-2 and MMP9 and up-regulation of Bax in BGC-823 cell. Inversely, overexpression of TRAF6 in SGC-7901 cells increased protein levels of phosphor-Akt, Bcl-2 and MMP9 and down-regulation of Bax. CONCLUSIONS: The expression of TRAF6 was positively correlated with an advanced N stage and acted as a predictor of a poor prognosis in patients with gastric cancer. Moreover, TRAF6 regulating cell apoptosis and invasive ability of gastric cancer cells might be associated with Akt activation and alterations of protein expression of Bcl2, Bax and MMP9.

[The expressions and meanings of BMP-7 and TGF-ß in idiopathic pulmonary fibrosis and idiopathic nonspecific interstitial pneumonia].

OBJECTIVE: To investigate the expressions of cytokines in idiopathic pulmonary fibrosis (IPF) and in idiopathic nonspecific interstitial pneumonia (INSIP); To discuss expressions and meanings of bone morphogenetic protein 7 (BMP-7) and transforming growth factor beta (TGF-ß) in IPF and IPF. METHODS: Selected 47 cases of idiopathic interstitial pneumonia (IIP), which were diagnosed by clinical-radiologic-pathologic (CRP), and classified into two groups which were group IPF (25 IPF) and group INSIP (22 INSIP, including 6 cellular pattern and 16 fibrosing pattern). The normal lung tissues were collected as the control group: The fresh tissues were made to detect more than 114 kinds of cytokines' expressions via Oligo GEArray gene microarray technology. Made a tissue microarray which applied EnVision immunohistochemistry technology to detect the expressions of BMP-7 and TGF-ß in both kinds of IIPs. The two groups of patients were followed-up visited around 5 to 8 years and the survival curves were evaluated by Kaplan-Meier method. RESULTS: According to gene microarray results, these two groups were up-expression in TGF family,IL family and TNF family. Most of BMP members were down-expression, in comparison with the control group, except BMP-5,BMP-8B and BMP-15. As the tissue microarray results demonstrated, compared with normal lung tissues,BMP-7 expressed decreasingly in IPF and INSIP groups (t1 = 27.618, P < 0.001; t2 = -12.404, P < 0.001). The expression of IPF were lower than INSIP (t = 5.387, P < 0.05); In INSIP group, patients of cellular pattern expressed BMP-7 more than fibrosing pattern's (t = -5.341, P < 0.001). There were dramatically increasing expressions of TGF-ß in IPF and INSIP, when compared with the control group (t1 = 23.393, P < 0.001; t2 = -13.445, P < 0.001) and it presented negative correlation with BMP-7(group IPF: r = -0.771, P < 0.001; group INSIP: r = -0.729, P < 0.001). (3) Clinical follow-up data showed, the stability(improvement), deterioration and death rates of the group IPF and the group INSIP were, respectively, 0(0%), 2 (8%), 23 (92%) and 15 (68.1%), 3 (13.6%), 4 (18.2%). The results were statistically significant (all P < 0.05). The median survival time of the part with higher BMP-7 expression and the part with relatively lower BMP-7 expression, in the group IPF, were 110.8 and 66.4 months (t = -2.686, P < 0.05); In the group INSIP, were 146.4 and 74.9 months (t = -3.037, P < 0.05). CONCLUSIONS: Cellular cytokines presented different expression profiles in IPF and INSIP patients. Differently with highly activated TGF-ß, BMP-7 was inhibited in IIP patients, which would remind the degree of fibrosis and prognosis of IIP. BMP-7 would be expected to be a novel target for IIP pathogenesis and prognostic research.

Protein-protein interaction analysis of distinct molecular pathways in two subtypes of colorectal carcinoma.

The aim of this study was to identify the molecular events that distinguish serrated colorectal carcinoma (SCRC) from conventional colorectal carcinoma (CCRC) through differential gene expression, pathway and protein-protein interaction (PPI) network analysis. The GSE4045 and GSE8671 microarray datasets were downloaded from the Gene Expression Omnibus database. We identified the genes that are differentially expressed between SCRC and normal colon tissues, CCRC and healthy tissues, and between SCRC and CCRC using Student's t-tests and Benjamini­Hochberg (BH) multiple testing corrections. The differentially expressed genes (DEGs) were then mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and their enrichment for specific pathways was investigated using the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool with a significance threshold of 0.1. Analysis of the potential interactions between the protein products of 220 DEGs (between CCRC and SCRC) was performed by constructing a PPI network using data from the high performance RDF database (P<0.1). The interaction between pathways was also analyzed in CCRC based on the PPI network. Our study identified thousands of genes differentially expressed in SCRC and CCRC compared to healthy tissues. The DEGs in SCRC and CCRC were enriched in cell cycle, DNA replication, and base excision repair pathways. The proteasome pathway was significantly enriched in SCRC but not in CCRC after BH adjustment. The PPI network showed that tumour necrosis factor receptor-associated factor 6 (TRAF6) and atrophin 1 (ATN1) were the most central genes in the network, with respective degrees of node predicted at 90 and 88. In conclusion, the preoteasome pathway was shown to be specifically enriched in SCRC. Furthermore, TRAF6 and ATN1 may be promising biomarkers for the distinction between serrated and conventional CRC.

[Effects of 1, 25 (OH)2D3 on bleomycin-induced pulmonary fibrosis in mice].

OBJECTIVE: To observe the effects of 1, 25(OH)2D3 on bleomycin-induced pulmonary fibrosis in mice and to explore its mechanisms. METHODS: Ninety male C57BL/6 mice, 6 to 8 weeks old, were randomly divided into 3 groups according to the table of random numbers: a control group, a model group and a treatment group(n = 30 each). Bleomycin was injected to the mice in the latter 2 groups by single intratracheal injection to duplicate the pulmonary fibrosis model, while the control group was injected with saline. From the next day, the mice in the treatment group received 1, 25 (OH) 2D3 (0.5 µg·kg(-1)·d(-1)) diluted in olive oil by gavage daily, while the other groups were treated with equivalent olive oil. Ten mice in each group were killed randomly on day 14, 21 and 28 after surgery respectively. Pulmonary alveolitis and fibrosis were evaluated by using hematoxylin-eosin and Masson stain method. The content of hydroxyproline was measured by acid hydrolysis method. The mRNA levels of collagen1α1, α-SMA, Wnt3a, Wnt4, and Wnt7a in the lung tissues were measured by real-time RT-PCR, while the protein expression of α-SMA and ß-catenin were assessed by immunohistochemistry. RESULTS: Pulmonary alveolitis at day 14, 21 and fibrosis at day14, 21, 28 in the treatment group were remarkably reduced compared to the model group (all P < 0.05). Compared with the model group, the treatment group showed decreased content of hydroxyproline, decreased mRNA levels of collagen1α1, α-SMA, Wnt3a, Wnt4 and decreased protein expression of α-SMA and ß-catenin at the 3 time points (all P < 0.05). The content of hydroxyproline and the mRNA levels of collagen1α1, α-SMA, Wnt3a, Wnt4, Wnt7a in the treatment group at 28 d were 0.67 ± 0.14, 1.66 ± 0.34, 1.37 ± 0.41, 1.43 ± 0.27, 1.29 ± 0.19, 1.18 ± 0.20, respectively, all of which were significantly lower than those in the model group (1.10 ± 0.16, 3.50 ± 0.74, 2.68 ± 0.61, 2.60 ± 0.58, 2.23 ± 0.45, 1.93 ± 0.36, respectively). Protein expression of α-SMA and ß-catenin in the treatment group were 0.44 ± 0.13 and 0.25 ± 0.05, respectively, which were also significantly lower than those of the model group(0.98 ± 0.20, 0.58 ± 0.06, respectively). CONCLUSION: 1, 25 (OH) 2D3 was shown to reduce pulmonary fibrosis induced by bleomycin in mice, and its mechanisms might be associated with Wnt signaling suppression.