A Novel Method for Pathway Identification Based on Attractor and Crosstalk in Polyarticular Juvenile Idiopathic Arthritis.

BACKGROUND Juvenile idiopathic arthritis (JIA) is one of the most common inflammatory disorders of unknown etiology. We introduced a novel method to identify dysregulated pathways associated with polyarticular JIA (pJIA). MATERIAL AND METHODS Gene expression profiling of 61 children with pJIA and 59 healthy controls were collected from E-GEOD-13849; 300 pathways were obtained from Kyoto Encyclopedia of Genes and Genomes (KEGG) database and 787,896 protein-protein interaction sets were gathered from the Retrieval of Interacting Genes. Attractor and crosstalk were designed to complement each other to increase the integrity of pathways assessment. Then, impact factor was used to assess the interactions inter-pathways, and RP-value was used to evaluate the comprehensive influential ability of attractors. RESULTS There were seven attractors with p<0.01 and 14 pathways with RP<0.01. Finally, two significantly dysfunctional pathways were found, which were related to pJIA progression: p53 signaling pathway (KEGG ID: 04115) and non-alcoholic fatty liver disease (NAFLD) (KEGG ID: 04932). CONCLUSIONS A novel approach that identified the dysregulated pathways in pJIA was constructed based on attractor and crosstalk. The new process is expected to be efficient in the upcoming era of medicine.

[Clinical efficiency and activity range of stiff knee by total knee arthroplasty].

OBJECTIVE: To observe clinical effect and influencing factor of total knee arthroplasty (TKA) for the treatment of stiff knee. METHODS: From January 2010 to October 2014, 20 patients(25 knees) with stiff knee were treated with TKA. Among them, including 2 males(3 knees) and 18 females(22 knees), aged from 55 to 78 years old with an average of(64.5± 4.9) years old, the courses of disease ranged from 5 to 21 years with an average 8.3 years. Preoperative and postoperative HSS (hospital for special surgery knee score) score, activity range and complications were observed and compared. RESULTS: All patients were followed up from 12 to 69 months with an average of 35.3 months. Ten patients occurred complications after operation. HSS score was improved from 32.36±12.31 preoperatively to 80.70±18.52 postoperatively, and had statistical difference between two groups;7 knees obtained excellent results, 15 knees good and 3 knees moderate. Activity range was improved from(39.4±5.3)°preoperatively to (92.5±11.2)° at the latest follow up. CONCLUSIONS: Total knee arthroplasty for stiffness knees is feasible and could obtain satisfied activity range and function.

Pathway analysis based on Monte Carlo Cross-Validation in polyarticular juvenile idiopathic arthritis.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is a common chronic disease with onset before the 16 years old in a child. Polyarticular JIA has been reported as the main form of JIA in several locations. Until now, understanding of the genetic basis of JIA is incomplete. The purpose of this study was to identify pathway pairs of great potential functional relevance in the progression of polyarticular JIA. MATERIALS AND METHODS: Microarray data of 59 peripheral blood samples from healthy children and 61 samples from polyarticular JIA were transformed to gene expression data. Differential expressed genes (DEG) between patients and normal controls were identified using Linear Models for Microarray Analysis. After performed enrichment of DEG, differential pathways were identified with Fisher's test and false discovery rate. Differential pathway pairs were constructed with random two differential pathways, and were evaluated by Random Forest classification. Monte Carlo Cross-Validation was introduced to screen the best pathway pair. RESULTS: 42 DEG with P-values<0.01 were identified. 19 differential pathways with P-values<0.01 were identified. Area under the curve (AUC) of pathway pairs was generated with RF classification. After 50 bootstraps of Monte Carlo Cross-Validation, the best pathway pair with the highest AUC value was identified, and it was the pair of tumoricidal function of hepatic natural killer cells pathway and erythropoietin signaling pathway. CONCLUSION: These identified pathway pairs may play pivotal roles in the progress of polyarticular JIA and can be applied for diagnosis. Particular attention can be focused on them for further research.