[Transcription factors analysis of subchondral bone in early experimental osteoarthritis based on gene expression profiles].

OBJECTIVE: To identify the master transcription factors (TF) that might be responsible for the gene expression alteration of OA. METHODS: Raw expression data for rat OA model(GSE30322) was downloaded from NCBI GEO database. Microarray data analysis for rat and human was carried out separately using functions from limma packagein R, gene expression was considered as significantly changed between conditions if adjusted P-value<0.05 and the absolute value of fold change>=2. iRegulon was applied to differentially up-regulated and down-regulated genes in OA separately. RESULTS: (1)15 TFs, including FOXN4, NANOS1, E2F6, RAD21, MECOM, ETS1, MEF2A, POU2F3, BRCA1, GATA3, ZNF706, ZBTB33, SUZ12, DBP and SETDB1, were identified as the potential master TFs of up-regulated DEGs with statistical significance. (2)12 TFs, including ARID3A, YY1, RDBP, ATF1, CRX, TAF1, XBP1, SOX3, E2F4, PGR, TIMM8A and HOXA2, were identified as the potential master TFs of down-regulated DEGs with statistical significance. CONCLUSIONS: The newly identified TFs maybe play important roles in pathogenesis of early experimental osteoarthritis, and our study provides new diagnostic markers or therapeutic targets for OA.

The impact of laparoscopic converted to open colectomy on short-term and oncologic outcomes for colon cancer.

PURPOSE: This study was designed to evaluate the impact of laparoscopic converted to open colectomy on short-term and oncologic outcomes and to identify risk factors for long-term survival in patients undergoing colectomy for non-metastatic colon cancer. METHODS: A prospective database of consecutive operations for non-metastatic colon cancer was reviewed. Patients were grouped as conversion (CONV) group, completed laparoscopic resection (LAP) group, or open resection (OPEN) group. The clinical and perioperative parameters, pathologic features, and oncologic outcomes were collected. Univariate analysis was performed for comparing these data. Patients without evidence of recurrence at last follow-up or still alive at the end of study period were censored. Kaplan-Meier curves were utilized to analyze survival. A multivariate analysis was performed to identify predictors of poor disease-free survival (DFS) and overall survival (OS). RESULTS: The conversion rate was 15.2 %. The most common reason for conversion was locally advanced cancer (45.5 %). Converted patients were associated with a longer operative time (188 ± 29.1 min, P < 0.001), greater blood loss (147 ± 14 mL, P < 0.001), and a higher rate of intra-operative complications (15.2 %, P = 0.042) compared to the completely laparoscopic or open patients. Days to flatus, early ambulation, and length of hospitalization were significantly shorter in completed laparoscopic resection (LAP) group (P < 0.001); however, the outcomes were comparable between conversion (CONV) and open resection (OPEN) groups. The incidence of wound infection was significantly higher in the OPEN group than in the LAP group (P = 0.005), whereas there were no significant differences observed between the CONV group and the OPEN group (P = 1.000) or between the LAP group and the CONV group (P = 0.073). The 5-year DFS in CONV patients (46.5 %) was comparable to LAP patients (55.5 %, P = 0.138) and OPEN patients (59.1 %, P = 0.113). Moreover, there were no significant differences noted in terms of the 5-year OS in the CONV group (56.7 %) compared to the LAP group (67.3 %, P = 0.317) or the OPEN group (66.3 %, P = 0.420). The multivariate analysis showed that pT3-4 cancer (P < 0.001) and poor differentiation (P < 0.001) were independent predictors of both lower OS and lower DFS, whereas leakage (P = 0.008) and lack of adjuvant chemotherapy (P = 0.023) were independent risk factors only of lower DFS. CONCLUSION: Conversion to open colectomy from an initial laparoscopic approach does not worsen the long-term survival in patients with non-metastatic colon cancer.

[Expression of lipoprotein related genes in subchondral bone of early experimental osteoarthritis].

OBJECTIVE: To study the expression of lipoprotein related genes in subchondral bone of early experimental os-teoarthritis, which may play an important role in the pathogenesis of osteoarthritis. METHODS: Animals are equally divided into two groups: experimental group and control group, both of which contain fifteen rats of similar weight. The right knee joints of experimental group underwent surgery,which involved in both medial collateral ligament(MCL) transaction and medial meniscectomy, while the control group was only carried out with a sham operation. Rats were killed at 1, 2 and 4 weeks postsurgery to obtain the right knee joints. Total RNA of the subchondral bone was extracted,and then hybridized to Agilent Whole Rat Genome Microarray. Differentially expressed genes analysis was used to study the chemokine signaling pathway. RESULTS: Apoa5 expression was down-regulated at 1, 2 weeks post-surgery, Apoc2 expression was up-regulated at 1 week after surgery, Apol3 expression was up-regulated at 1 and down-regulated at 4 weeks post-surgery, Lrp1 expression was down-regulated at 1, 2 weeks after surgery. Lrp5 was down-regulated at 2 weeks after surgery. Gpihbp1, Lpl, Tfpi and Vldlr were up-regulated at 1 weeks after surgery. Lrpap1 and RGD1309808 were down-regulated at 4 weeks after surgery. CONCLUSION: Dysregulation of lipoprotein related genes plays an important role in pathogenesis of early experimental osteoarthritis.

Effects of sevoflurane pretreatment on renal Src and FAK expression in diabetic rats after renal ischemia/reperfusion injury.

The diabetic kidney is sensitive to ischemia-reperfusion (I/R) injury due to microvascular complications, such as cellular apoptosis and necrosis. The aim of this study was to determine if sevoflurane pretreatment could help preserve renal function in rats with diabetes mellitus (DM) by altering non-receptor tyrosine kinases steroid receptor coactivator (Src) and focal adhesion kinase (FAK) expression (Src and FAK are mediators of cellular apoptosis and necrosis). Male rats (N = 40) were randomly assigned to one of five groups: Group A, sham operation; Group B, renal I/R injury; Group C, DM + sham operation; Group D, DM + renal I/R injury; and Group E, DM + sevoflurane pretreatment + renal I/R injury. Sevoflurane pretreatment comprised exposure to 2.5 % sevoflurane for 30 min, followed by exposure to air for 10 min. After 24 h, serum creatinine (Cr) and blood urea nitrogen (BUN) levels, and renal Src and FAK expression (immunohistochemistry) were assessed. Compared with rats in C, rats in D had significantly higher Cr and BUN levels, but significantly lower renal Src and FAK expression. Rats in E had significantly lower serum Cr and BUN levels and significantly higher renal Src and FAK expression levels than rats in D. Our findings suggest that sevoflurane pretreatment in rats with DM protects the kidneys from ischemia/reperfusion injury in part due to increased renal Src and FAK expression.