Orthographic Processing of Developmental Dyslexic Children in China: Evidence from an Event-Related Potential Study.

OBJECTIVE: This study aimed to explore the orthographic processing of simplified Chinese characters in developmental dyslexic children in Kashgar, Xinjiang, China, and provide a theoretical basis for intervention strategies for developmental dyslexia in Chinese. METHODS: Using event-related potential (ERP) measures, 18 developmental dyslexic children and 23 typically developing children performed a character decision task with three types of stimuli: real characters (RCs), pseudocharacters (PCs), and noncharacters (NCs). RESULTS: Behavioral results showed that the control children displayed a faster and higher accurate performance than the dyslexic children across PCs and NCs. ERP data revealed that the RCs and PCs elicited a stronger P200 than the NCs. Compared with the RCs and NCs, children in the control group showed more N400 negatives for PCs. It is worth mentioning that dyslexic children did not show any difference on N400, which reflected the insufficient orthographic processing of dyslexic children in China. CONCLUSION: These results show that Chinese dyslexic children had orthographic processing defects.

Non-coding RNA Identification in Osteonecrosis of the Femoral Head Using Competitive Endogenous RNA Network Analysis.

OBJECTIVE: To investigate the regulatory network of long non-coding RNA (lncRNA) as competing endogenous RNAs (ceRNAs) in osteonecrosis of the femoral head (ONFH). METHODS: The gene expression profile GSE74089 of ONFH and microRNA (miRNA) expression profile of GSE89587 were obtained from the Gene Expression Omnibus (GEO) database. The GSE74089 contained four ONFH samples and four controls. The GSE89587 included 10 ONFH samples and 10 control samples. The differentially expressed lncRNAs (DE-lncRNAs) and DE-mRNAs between ONFH group and control group were identified from GSE74089 using the limma package based on criteria of adjusted P value <0.05 and |log fold change (FC)| ≥2. The DEmiRNAs between ONFH group and control group were screened from GSE89587 on the basis of adjusted P value <0.05. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway for DE-mRNAs were analyzed using DAVID 6.7 and GSEA 3.0, respectively. Coexpressed lncRNA-mRNA pairs were identified by corr.test method in R based on the criteria of adjusted P value <0.01 and |r| ≥ 0.9. A ceRNA network was constructed and visualized using cytoscape 3.7.0 by integrating the DE-lncRNA, DE-miRNA, and DEmRNA data. The key mRNAs and lncRNAs in the ceRNA network were further validated in an independent dataset of GSE123568. RESULTS: Based on our analysis, a total of 28 DE-lncRNAs, 1403 DE-mRNAs, and 134 DE-miRNAs were identified, respectively. The DE-mRNAs were significantly enriched in the function of "skeletal system development," "collagen fibril organization," "blood vessel development," and "regulation of nervous system development." Besides, 72 KEGG pathways, including eight active pathways and 64 suppressed pathways were identified, including which immune pathway was the most significantly activated one and which ribosome-related function was the most suppressed. A co-expression network including 161 DE-mRNAs and 16 DE-lncRNAs was built. Highly connected nodes were identified among lncRNAs such as H19, C20orf203, LINC00355, SFTA3, CRNDE, CASC2, LINC00494, C9orf163, C10orf91, and LINC00301. The ceRNA network indicated that lncRNA H19 functioned as a ceRNA of hsa-miR-519b-3p and hsa-miR-296-5p in ANKH and ECHDC1 regulation; lncRNA C9orf163 functioned as a ceRNA of hsa-miR-424-5p in CCNT1 regulation. The expression trends of ANKH, CCNT1, and C9orf163 were successfully validated in independent dataset of GSE123568. CONCLUSION: The ceRNAs of lncRNA H19- hsa-miR-519b-3p/hsa-miR-296-5p-ANKH and lncRNA c9orf163- hsa-miR-424-5p-CCNT1 might play important roles in ONFH development. Our research provided an understanding of the important role of lncRNA-related ceRNAs in ONFH.

Baicalin inhibits C2C12 myoblast apoptosis and prevents against skeletal muscle injury.

Anti­apoptotic and anti­inflammatory treatments are imperative for skeletal muscle regeneration following injury. Baicalin is well known and has previously been investigated for its role in the treatment of injury and inflammatory diseases. Therefore, the present study aimed to investigate the effects of baicalin in inhibiting apoptosis of C2C12 myoblasts and preventing skeletal muscle injury. A cell counting kit­8 (CCK­8) assay and Annexin V/PI staining were initially performed to measure cell viability and apoptosis under conditions of H2O2 exposure with or without baicalin. Subsequently, oxidative activity, mitochondrial function, mitochondrial apoptogenic factors and caspase proteins were analyzed to examine the mechanism underlying the effect of baicalin on inhibiting apoptosis in C2C12 myoblasts. Furthermore, BALB/C mice with skeletal muscle injuries were established, and the potential application of baicalin for anti­apoptotic and anti­inflammatory effects was examined via small animal ß­2­[18F]­fluoro­2­deoxy­D­glucose (18F­FDG) positron emission tomography (PET) imaging and pathological examination. The CCK­8 assay and Annexin V/PI staining revealed cell death in the C2C12 myoblasts induced by H2O2, which was apoptotic, and this was effectively reversed by treatment with baicalin. H2O2 increased the reactive oxygen species and malondialdehyde levels in C2C12 myoblasts, which was caused by mitochondrial dysfunction, decreased expression of cytochrome c and apoptosis­inducing factor from cytosolic and mitochondrial fractions, and activated expression of caspase­3 and caspase­9; however, treatment with baicalin reversed these effects. In addition, small animal PET imaging revealed that treatment with baicalin decreased the accumulation of FDG by ~65.9% in the injured skeletal muscle induced by H2O2. These pathological results also confirmed the protective effect of baicalin on injured skeletal muscle. Taken together, the results of the present study indicated that baicalin effectively inhibited the apoptosis of C2C12 myoblasts and protected skeletal muscle from injury, which may have potential therapeutic benefits for patients in a clinical setting.

Baicalin prevents the apoptosis of endplate chondrocytes by inhibiting the oxidative stress induced by H2O2.

Osteoarthritis (OA) is a degenerative disease of articular cartilage. The pathogenesis of OA remains to be fully elucidated, and several studies have found that oxidative stress is important in its pathogenesis. Baicalin is well known and has already been investigated for its role of inhibiting the oxidative stress pathway. Thus, the present study aimed to investigate the role of baicalin on the inhibition of oxidative stress in endplate chondrocytes induced by hydrogen peroxide (H2O2). Following treatment of endplate chondrocytes with different doses of H2O2 with or without baicalin for different incubation durations, a CCK­8 assay and Annexin V/PI staining were used to measure the cell proliferation and apoptotic rates to identify the optimal experimental conditions. Subsequently, for examining the effects and underlying mechanism of baicalin on oxidative stress, the protein expression levels of cleaved­poly (ADP­ribose) polymerase (PARP), B­cell lymphoma­2­associated X protein (Bax) and pro­caspase­3 were analyzed using western blot analysis, intracellular anti­oxidant activities, including those of malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO), were quantified, and the levels of endothelial nitric oxide synthase (eNOS) were examined using reverse transcription­polymerase chain reaction analysis. The results revealed that the oxidative stress of endplate chondrocytes induced by 0.5 mM H2O2 for 4 h were the most appropriate conditions for experiments, and pretreatment with 100 µmol/l baicalin for 1 h effectively reversed the effect of H2O2 on the endplate chondrocytes. In addition, Annexin V/PI staining demonstrated that the cell death induced by H2O2 was apoptotic, and baicalin reversed the apoptosis induced by oxidative stress. H2O2 activated PARP cleavage, and the expression of Bax and pro­caspase­3; however, baicalin inhibited the expression of these apoptotic signaling indicators. Baicalin also reduced the levels of MDA, and increased the levels of SOD and NO. Baicalin also significantly elevated the mRNA levels of eNOS in endplate chondrocytes. Therefore, the results of the present study showed that baicalin significantly inhibited the oxidative stress in endplate chondrocytes induced by H2O2, and decreased cell apoptosis.

Inhibition of ERK1/2 Signaling Pathway is Involved in Melatonin's Antiproliferative Effect on Human MG-63 Osteosarcoma Cells.

BACKGROUND: In a previous study, we found that melatonin inhibits MG-63 osteosarcoma cell proliferation; however, the underlying mechanisms remain elusive. Mitogen-activated protein kinase (MAPK) and Akt signaling pathways play key roles in the anticancer effects of melatonin. AIMS: The present study investigated whether MAPK and Akt signaling pathways are involved in melatonin's antiproliferative actions on the human MG-63 osteosarcoma cells. METHODS/RESULTS: Western blot analysis confirmed that melatonin significantly inhibited phosphorylation of ERK1/2 but not p38, JNK, or Akt. The expression of ERK1/2, p38, JNK, and Akt was not altered by melatonin. PD98059 and melatonin alone, and especially in combination, significantly inhibited cell proliferation. The changes included G1 and G2/M phase arrest of the cell cycle, and a downregulation of the expression at both the protein and mRNA levels of cyclin D1 and CDK4 (related to the G1 phase) and of cyclin B1 and CDK1 (related to the G2/M phase) as measured by flow cytometry after propidium iodide staining, and both western blot and real-time PCR, respectively. Furthermore, the combination of PD98059 and melatonin synergistically and markedly augmented the action of either agent alone. Co-immunoprecipitation further confirmed that there was an interaction between p-ERK1/2 and cyclin D1, CDK4, cyclin B1, or CDK1, which was blunted in the presence of melatonin or PD98059. CONCLUSION: These findings suggest that melatonin's antiproliferative action is mediated by inhibition of the ERK1/2 signaling pathway rather than the p38, JNK, or Akt pathways.

P-glycoprotein overexpression in bone marrow-derived multipotent stromal cells decreases the risk of steroid-induced osteonecrosis in the femoral head.

P-glycoprotein (P-gp) plays a role in steroid-induced osteonecrosis of the femoral head (ONFH), but the underlying mechanism remains unknown. We hypothesized that P-gp overexpression can prevent ONFH by regulating bone marrow-derived multipotent stromal cell (BMSC) adipogenesis and osteogenesis. BMSCs from Sprague-Dawley rats were transfected with green fluorescent protein (GFP) or the multidrug resistance gene 1 (MDR1) encoding GFP and P-gp. Dexamethasone was used to induce BMSC differentiation. Adipogenesis was determined by measuring peroxisome proliferator-activated receptor (PPAR-γ) expression and the triglyceride level. Osteogenesis was determined by measuring runt-related transcription factor 2 (Runx2) expression and alkaline phosphatase activity. For in vivo experiments, rats were injected with saline, BMSCs expressing GFP (GFP-BMSCs) or BMSCs expressing GFP-P-gp (MDR1-GFP-BMSCs). After dexamethasone induction, adipogenesis was determined by measuring PPAR-γ expression and fatty marrow, whereas osteogenesis was detected by measuring Runx2 expression, trabecular parameters and the mineral apposition rate, followed by evaluation of the incidence of ONFH. Overexpression of P-gp in BMSCs resulted in markedly decreased expression of adipogenic markers and increased expression of osteogenic markers. Compared with rats injected with saline, rats injected with GFP-BMSCs showed reduced ONFH, and the injected GFP-positive BMSCs attached to trabecular surfaces and exhibited an osteoblast-like morphology. Compared with the rats injected with BMSCs expressing GFP alone, rats injected with BMSCs overexpressing GFP and P-gp showed lower adipocytic variables, higher osteogenic variables and lower incidence of ONFH. Overexpression of P-gp inhibited BMSC adipogenesis and promoted osteogenesis, which reduced the incidence of steroid-induced ONFH.

Regulatory mechanisms underlying sepsis progression in patients with tumor necrosis factor-α genetic variations.

The present study aimed to investigate the regulatory mechanisms underlying sepsis progression in patients with tumor necrosis factor (TNF)-α genetic variations. The GSE5760 expression profile data, which was downloaded from the Gene Expression Omnibus database, contained 30 wild-type (WT) and 28 mutation (MUT) samples. Differentially expressed genes (DEGs) between the two types of samples were identified using the Student's t-test, and the corresponding microRNAs (miRNAs) were screened using WebGestalt software. An integrated miRNA-DEG network was constructed using the Cytoscape software, based on the interactions between the DEGs, as identified using the Search Tool for the Retrieval of Interacting Genes/Proteins database, and the correlation between miRNAs and their target genes. Furthermore, Gene Ontology and pathway enrichment analyses were conducted for the DEGs using the Database for Annotation, Visualization and Integrated Discovery and the KEGG Orthology Based Annotation System, respectively. A total of 390 DEGS between the WT and MUT samples, along with 11 -associated miRNAs, were identified. The integrated miRNA-DEG network consisted of 38 DEGs and 11 miRNAs. Within this network, COPS2 was found to be associated with transcriptional functions, while FUS was found to be involved in mRNA metabolic processes. Other DEGs, including FBXW7 and CUL3, were enriched in the ubiquitin-mediated proteolysis pathway. In addition, miR-15 was predicted to target COPS2 and CUL3. The results of the present study suggested that COPS2, FUS, FBXW7 and CUL3 may be associated with sepsis in patients with TNF-α genetic variations. In the progression of sepsis, FBXW7 and CUL3 may participate in the ubiquitin-mediated proteolysis pathway, whereas COPS2 may regulate the phosphorylation and ubiquitination of the FUS protein. Furthermore, COPS2 and CUL3 may be novel targets of miR-15.

Time course analysis based on gene expression profile and identification of target molecules for colorectal cancer.

BACKGROUND: The study aimed to investigate the expression changes of genes in colorectal cancer (CRC) and screen the potential molecular targets. METHODS: The GSE37178 of mRNA expression profile including the CRC samples extracted by surgical resection and the paired normal samples was downloaded from Gene Expression Omnibus database. The genes whose expressions were changed at four different time points were screened and clustered using Mfuzz package. Then DAVID was used to perform the functional and pathway enrichment analysis for genes in different clusters. The protein-protein interaction (PPI) networks were constructed for genes in the clusters according to the STRING database. Furthermore, the related-transcription factors (TFs) and microRNAs (miRNAs) were obtained based on the resources in databases and then were combined with the PPI networks in each cluster to construct the integrated network containing genes, TFs and miRNAs. RESULTS: As a result, 314 genes were clustered into four groups. Genes in cluster 1 and cluster 2 showed a decreasing trend, while genes in cluster 3 and cluster 4 presented an increasing trend. Then 18 TFs (e.g., TCF4, MEF2C and FOS) and 18 miRNAs (e.g., miR-382, miR-217, miR-1184, miR-326 and miR-330-5p) were identified and three integrated networks for cluster 1, 3, and 4 were constructed. CONCLUSIONS: The results implied that expression of PITX2, VSNL1, TCF4, MEF2C and FOS are time-related and associated with CRC development, accompanied by several miRNAs including miR-382, miR-217, miR-21, miR-1184, miR-326 and miR-330-5p. All of them might be used as potential diagnostic or therapeutic target molecules for CRC.

Bioinformatics Analysis of microRNA Time-Course Expression in Brown Rat (Rattus norvegicus): Spinal Cord Injury Self-Repair.

STUDY DESIGN: This is a bioinformatic study designed to investigate the time-course expression changes of microRNAs (miRNAs) after spinal cord injury (SCI). OBJECTIVE: To investigate the mechanism of SCI self-repair at miRNAs level and target genes level. SUMMARY OF BACKGROUND DATA: SCI results in loss of sensory and locomotor function, and SCI self-repair might provide clinical therapies; however, the mechanism of SCI self-repair remains unclear. METHODS: The miRNA expression profile (GSE19890) of adult female Wistar brown rats (Rattus norvegicus) in SCI (laminectony and contusion), sham (laminectony but no contusion), and control (untreated) groups was downloaded from Gene Expression Omnibus. Totally, 35 chips were available, including five controls, five SCI-1-day, five SCI-3-day, five SCI-7-day, five sham-1-day, five sham-3-day, and five sham-7-day. Betr and limma package were used to screen time-course differentially expressed miRNAs (DEmiRNAs), followed by Bayesian hierarchical clustering (BHC), synergetic and functional enrichment analysis through BHC and cluster Profiler packages, respectively. Furthermore, STRING database and Cytoscape software were used to construct interaction networks between time-course DEmiRNAs, and GenCLip2.0 software was applied to pathway enrichment for key genes associated with nervous system. RESULTS: Totally, 68 time-course DEmiRNAs were identified and divided into 15 BHC clusters. Then, 100 time-course DEmiRNA pairs with synergetic function were identified, and time-course DEmiRNAs and target genes interaction networks were constructed, in which 10 genes (AKT1, VEGFA, CTNNB1, IGF1, APP, PTEN, CDC42, BDNF, SOD2, and IFNG) with highest degrees were found. Furthermore, key genes were significantly enriched in neurotrophin signaling pathway. CONCLUSION: After SCI, miRNAs might collectively regulate target genes, facilitating or inhibiting self-repair. Modulation of these miRNAs might provide novel therapies for SCI treatment. LEVEL OF EVIDENCE: N/A.

GSK3ß expression and phosphorylation during neuronal maturation in the rat dorsal root ganglion.

Glycogen synthase kinase 3ß (GSK-3ß) protein is a key regulator of neurogenesis, neuronal differentiation and polarisation during neurodevelopment. Sensory neurons in dorsal root ganglion (DRG) undergo a series of development stages during its maturation. In this study, we investigated the dynamic changes in GSK-3ß expression and phosphorylation of its N-terminal serine-9 residue (p-GSK-3ß (S9)) during DRG development. Sprague-Dawley (SD) rats were divided according to the following ages: Embryonic 13(th) (E13), E15, E19, Postnatal 1(st) (P1), P3, P7, P14, P21 and P60 days. GSK-3ß was detected by immunohistochemistry and double immunofluorescence on DRGs. Western blotting was used to determine the quantity of GSK-3ß and p-GSK-3ß (S9) expression. It was found that GSK-3ß immunopositive cells in the DRG appeared as early as E13 development phase, and gradually increased to a peak level at P3, at which almost all neurons were GSK-3ß positive, and then stayed at a high level to the experiment day 60. GSK3ß expression was cell-type-specific during DRG maturation and exhibited cytoplasmic staining in the neuronal cell body and the axon. Glial cells consistently remained negative in DRGs at all stages. Western blot analysis revealed that GSK3ß expression stayed the same during DRG maturation. In contrast, p-GSK-3ß (S9) expression was stage-specific and decreased from E13 to P60 (P < 0.01). Taken together, these results suggest that GSK-3ß expression is stage-specific and cell-type-specific during DRG maturation.

Prediction of feature genes in trauma patients with the TNF rs1800629 A allele using support vector machine.

BACKGROUND: Tumor necrosis factor (TNF)-α variant is closely linked to sepsis syndrome and mortality after severe trauma. We aimed to identify feature genes associated with the TNF rs1800629 A allele in trauma patients and help to direct them toward alternative successful treatment. METHODS: In this study, we used 58 sets of gene expression data from Gene Expression Omnibus to predict the feature genes associated with the TNF rs1800629 A allele in trauma patients. We applied support vector machine (SVM) classifier model for classification prediction combining with leave-one-out cross validation method. Functional annotation of feature genes was carried out to study the biological function using database for annotation, visualization, and integrated discovery (DAVID). RESULTS: A total of 133 feature genes were screened out and was well differentiated in the training set (14 patients with variant, 15 with wild type). Moreover, SVM classifier peaked in predictive accuracy with 100% correct rate in training set and 86.2% in testing set. Interestingly, functional annotation showed that feature genes, such as HMOX1 (heme oxygenase (decycling) 1) and RPS7 (ribosomal protein S7) were mainly enriched in terms of cell proliferation and ribosome. CONCLUSION: HMOX1 and RPS7 may be key feature genes associated with the TNF rs1800629 A allele and may play a crucial role in the inflammatory response in trauma patients. Moreover, the cell proliferation and ribosome pathway may contribute to the progression of severe trauma.

Decreased expression of microRNA-130a correlates with TNF-α in the development of osteoarthritis.

OBJECTIVE: Increased expression of tumor necrosis factor a (TNF-α) has emerged as an important inflammatory factor in osteoarthritis (OA) and other joint diseases. The study was performed to investigate whether the expression of TNF-α in human chondrocytes was regulated by miRNAs. METHODS: MiRNA-130a and TNF-α expression in cartilage specimens was examined in patients with knee osteoarthritis, chondrocytes and osteoarthritis rat model. Chondrocytes were transfected with siRNAs as a gene silencing methods. Expression of genes and proteins were analyzed by real-time PCR and western blotting respectively. RESULTS: Increased TNF-α and decreased miRNA-130a were observed in tissues from osteoarthritis patients. Moreover, we found a highly negitive correlation between miRNA-130a and TNF-α. Next, miRNA-130a loss-of-function increased the expression of TNF-α and promoted inflammation in chondrocytes. It was reasonable that miRNA-130a regulated a distinct underlying molecular and pathogenic mechanism of OA by forming a negative feedback loop with TNF-α. Furthermore, there were the abnormalities of bone metabolism in OA rat, which showed the miRNA-130a and TNF-α dysfunction that was one of important factors for the occurrence and development of OA. CONCLUSIONS: Our results indicated that miR-130a played an important role in regulating the expression of TNF-α in human chondrocytes and identified miR-130a as a novel therapeutic target in OA.

Identification of key genes associated with colorectal cancer based on the transcriptional network.

Colorectal cancer (CRC) is among the most lethal human cancers, but the mechanism of the cancer is still unclear enough. We aimed to explore the key genes in CRC progression. The gene expression profile (GSE4183) of CRC was obtained from Gene Expression Omnibus database which included 8 normal samples, 15 adenoma samples, 15 CRC samples and 15 inflammatory bowel disease (IBD) samples. Thereinto, 8 normal, 15 adenoma, and 15 CRC samples were chosen for our research. The differentially expressed genes (DEGs) in normal vs. adenoma, normal vs. CRC, and adenoma vs. CRC, were identified using the Wilcoxon test method in R respectively. The interactive network of DEGs was constructed to select the significant modules using the Pearson's correlation. Meanwhile, transcriptional network of DEGs was also constructed using the g: Profiler. Totally, 2,741 DEGs in normal vs. adenoma, 1,484 DEGs in normal vs. CRC, and 396 DEGs in adenoma vs. CRC were identified. Moreover, function analysis of DEGs in each group showed FcR-mediated phagocytosis pathway in module 1, cardiac muscle contraction pathway in module 6, and Jak-STAT signaling pathway in module 19 were also enriched. Furthermore, MZF1 and AP2 were the transcription factor in module 6, with the target SP1, while SP1 was also a transcription in module 20. DEGs like NCF1, AKT, SP1, AP2, MZF1, and TPM might be used as specific biomarkers in CRC development. Therapy targeting on the functions of these key genes might provide novel perspective for CRC treatment.

Comparison of Clinical Outcomes of Phalangeal Fracture Treated with Dorsolateral Approach or Post-middle Approach Using AO Mini Titanium Plate.

The aim of this study is to investigate the clinical outcomes of various fixation methods for proximal phalangeal fractures with Arbeitsgemeinschaft für Osteosynthesefragen (AO) mini titanium plate by dorsolateral approach or post-middle approach. Clinical results of 62 fingers of 53 patients with proximal phalangeal fracture were evaluated. For dorsolateral approach, the lateral bundle of the extensor tendon was drawn away to expose the fracture part of the bone. After reduction, the plate was located at the dorsolateral side of the bone. For post-middle approach, the extensor tendon was split to expose the fracture part of the bone. After reduction, the plate was fixed to the proximal phalangeal side of the bone, and the extensor tendon was repaired with 3-0 nonabsorbable silk sutures. We found low overall complication rates in both groups. The mean total active motion (TAM) for the dorsolateral group and post-middle group was 234.60° ± 22.63° and 221.08° ± 25.69°, respectively. There was a statistical significance between the two groups (P = 0.037 < 0.05), indicating that TAM was notably affected by various fixation methods. With AO mini titanium plate, movement in dorsolateral approach group was significantly higher than in post-middle approach group. Dorsolateral approach is an acceptable technique of incision for proximal phalangeal fractures.

Analysis of differentially expressed genes between rheumatoid arthritis and osteoarthritis based on the gene co-expression network.

The aim of the current study was to investigate disease-associated genes and related molecular mechanisms of osteoarthritis (OA) and rheumatoid arthritis (RA). Using GSE7669 datasets downloaded from Gene Expression Omnibus databases, the differentially expressed genes (DEGs) between RA and OA synovial fibroblasts (SFBs) (n=6 each) were screened. DEG-associated co-expression and topological properties were analyzed to determine the rank of disease-associated genes. Specifically, the fold change of differentially expressed genes, the clustering coefficient and the degree of differential gene co-expression were integrated to determine the disease-associated gene ranking. The underlying molecular mechanisms of these crucial disease-associated genes were investigated by gene ontology (GO) enrichment analysis. A total of 1313 DEGs, including 1068 upregulated genes and 245 downregulated genes were observed. The top 20 disease-associated genes were identified, including proteoglycan 4, inhibin ß B, carboxypeptidase M, alcohol dehydrogenase 1C and integrin ß2. The major GO biological processes of these top 20 disease-associated genes were highly involved in the immune system, such as responses to stimuli, immune responses and inflammatory responses. This large-scale gene expression study observed disease-associated genes and their associated GO function in RA and OA, which may provide opportunities for biomarker development and novel insights into the molecular mechanisms of these two diseases.

A retrospective analysis of reversed femoral Less Invasive Stable System (LISS) for treatment of subtrochanteric femoral fracture.

PURPOSE: This retrospective study aimed at investigating the indications, the surgical techniques and clinical results of treatment for unstable subtrochanteric fractures with reverse Less Invasive Stable System-distal femur (LISS-DF). METHODS: A total of twenty-six unstable subtrochanteric fracture patients were fixed with reverse LISS-DF from April 2005 to April 2008, including 17 (65%) males and 9 (35%) females with an average age of 43 years (ranged 35-56 years). Among them, 15 (57.7%) patients suffered road traffic accidents, and the remaining 11 (42.3%) patients had fall-related injuries. There were 16 patients with 32-A3.3 type, 4 with 32-A3.1 type and six with 32-A2.3 type fractures according to the AO classification. RESULTS: All patients were followed up after surgery for 28 months (ranged 24-35 months). All of the incisions healed primarily, and no postoperative complications were found, such as coax vara and femoral head perforation of screws. The average recovery time of all patients was 4 months (ranged 2-7 months), and the average Harris score was 85 points (ranged 71-98 points). CONCLUSIONS: Reverse LISS-DF is an effective operation for treatment of unstable subtrochanteric femoral fracture (AO classification, 32-A3.3, 32-A3.1 and 32-A2.3). Its advantages are minimal blood loss and reliable fixation.

Perforated sarcomatoid carcinoma of the jejunum: Case report.

Sarcomatoid carcinomas exhibit features that are common to epithelial and mesenchymal tumors. These carcinomas are rare, particularly in the small intestine. In the current case report, we describe a case of an intestinal sarcomatoid carcinoma in a 70-year-old Chinese female. Sarcomatoid carcinoma was confirmed based on light microscopy and immunohistochemical observations. The patient presented with symptoms of acute abdomen, which was due to an intestinal perforation caused by sarcomatoid carcinoma of the small bowel. Patients with sarcomatoid carcinoma are usually associated with a poor prognosis. However, this patient experienced a relatively favorable prognosis, which may be attributed to low positivity for Ki67 in the tumor.

C2ORF40 suppresses breast cancer cell proliferation and invasion through modulating expression of M phase cell cycle genes.

Recently, it has been suggested that C2ORF40 is a candidate tumor suppressor gene in breast cancer. However, the mechanism for reduced expression of C2ORF40 and its functional role in breast cancers remain unclear. Here we show that C2ORF40 is frequently silenced in human primary breast cancers and cell lines through promoter hypermethylation. C2ORF40 mRNA level is significantly associated with patient disease-free survival and distant cancer metastasis. Overexpression of C2ORF4 0 inhibits breast cancer cell proliferation, migration and invasion. By contrast, silencing C2ORF40 expression promotes these biological phenotypes. Bioinformatics and FACS analysis reveal C2ORF40 functions at G2/M phase by downregulation of mitotic genes expression, including UBE2C. Our results suggest that C2ORF40 acts as a tumor suppressor gene in breast cancer pathogenesis and progression and is a candidate prognostic marker for this disease.

Modulation of MAPK and Akt signaling pathways in proximal segment of injured sciatic nerves.

Mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3-kinase (PI3K)/Akt-mediated signaling pathways play critical roles in peripheral nerve injury. However, the mechanism by which activate these signaling is unclear. We examined the activation of MAPK and Akt pathways in the proximal segments of crushed rat sciatic nerve after 1-30 days injury. We found that the phosphorylation level of Erk was attenuated in protein level. Phosphorylation of JNK and p38 increased from day 1 to day 15 following injury. In addition, activation of Akt was up-regulated predominantly in the ipsilateral proximal nerves and located in Schwann cells. Furthermore, phosphorylated GSK3ß (Ser9) and GSK3ß (Tyr216) were highly augmented from the third day to the 30th day and from 3 to 7 days after injury, respectively. Moreover, mTOR/p70S6 were activated within 7 days injury. Taken together, our studies suggest that the PI3K/Akt signaling is required for the regulation of axon regeneration in Schwann cells in the proximal nerve segments after injury. Furthermore, the contralateral nerves have some compensable response to the injury, at least, including the changes of signaling molecules.