Downregulation of microRNA-217 and microRNA-646 acts as potential predictor biomarkers in progression, metastasis, and unfavorable prognosis of human osteosarcoma.

Despite the progress in therapeutic targets, it remains dissatisfactory for most osteosarcoma patients with metastasis or recurrence osteosarcoma. Therefore, it is required to determine the involved mechanisms of osteosarcoma. The aim of this study was to investigate the expression level of MiR-217 and miR-646 and also their association with clinicopathological features in patients with osteosarcoma. Total RNA was purified from patients with osteosarcoma and noncancerous bone tissues, and then quantitative real-time PCR was applied to evaluate the expression level of microRNAs. Our result suggested that miR-217 expression was remarkably deceased in osteosarcoma bone tissue when compared with noncancerous bone tissues (mean ± SD 5.32 ± 1.231, 2.01 ± 0.78; P = 0.024) and miR-646 expression decreased in osteosarcoma bone tissue in comparison with normal tissues (mean ± SD 4.56 ± 1.45, 1.76 ± 1.24; P = 0.041). Our findings indicated that decreased expression of MiR-217 and miR-646 was strongly correlated with high tumor, node, and metastasis (TNM) stage (P = 0.015, P = 0.002) and large cancer diameter (P = 0.041, P = 0.053). Kaplan-Meier survival and log-rank analysis indicated that shorter overall survival was strongly linked to decreased expression of miR-217 and miR-646 (log-rank test P = 0.034, P = 0.026). In terms of miR-217, multivariate Cox proportional hazards model analysis has showed that reduction of miR-217 expression (P = 0.001), TNM stage (P = 0.046), and lymph node metastasis (P = 0.006) were independently linked to a short-time survival of patients. In terms of miR-646, low expression of miR-646 (P = 0.021), TNM stage (P = 0.052), and tumor size (P = 0.043) were independently associated with poor survival of patients as prognostic factors. Our findings suggested that downregulation of MiR-217 and miR-646 was associated with progression of osteosarcoma. MiR-217 and miR-646 may play a key role in suppression of tumor in osteosarcoma and would be applied as a novel therapeutic agent.

Tissue expression levels of miR-29b and miR-422a in children, adolescents, and young adults' age groups and their association with prediction of poor prognosis in human osteosarcoma.

Osteosarcoma is the most common type of bone cancer in children and adolescents. MicroRNAs (miRNAs) play important roles in the development, differentiation, and function of different cell types and in the pathogenesis of various human diseases. miRNAs are differentially expressed in normal and cancer cells. The investigation of miRNA expression between healthy subjects and patients with osteosarcoma is crucial for future clinical trials. In this study, the expression levels of miRNAs were detected by qRT-PCR. Correlation between expression levels of tow miRNAs and different clinicopathological characteristics were analyzed using the χ (2) test. Survival rate was detected using the log-rank test and Kaplan-Meier method. qRT-PCR was shown that expression levels of miR-29b and miR-422a were strongly decreased in osteosarcoma bone tissue compared with noncancerous bone tissues. Our result indicated that the low expression levels of miR-29b and miR-422a showed strong correlation with large tumor size (P = 0.20; 0.029), advanced TNM stage (P = 0.001; 0.012), distant metastasis (P = 0.008; 0.019), and grade of tumor (P = 0.009; 0.016). Kaplan-Meier survival analysis showed that the low expressions of miR-29b/miR-422a were correlated with shorter time overall survival (log-rank test, P = 0.009; P = 0.013). Moreover, multivariate Cox proportional hazards model indicated that miR-29b and miR-422a (P = 0.024; P = 0.016) were independent prognostic markers of overall survival of patients. Our result indicated that downregulation of miR-29b and miR-422a may be linked to the prediction of poor prognosis, indicating that miR-29b and miR-422a may be a valuable prognostic marker for osteosarcoma patients.

The Relation Between Reflex Sympathetic Dystrophy Syndrome and Trauma Severity in Patients With Distal Tibia Fracture.

BACKGROUND: Reflex sympathetic dystrophy (RSD) syndrome is a multifactorial disorder with clinical features of neurogenic inflammation that causes hypersensitivity to pain or severe allodynia as well as blood flow problems, swelling, skin discoloration and maladaptive neuroplasticity due to vasomotor disorders. Patients with major trauma are prone to homeostasis leading to inflammatory response syndrome and multiple organ distress syndrome. Several studies have investigated the etiology of this condition, but the cause remains unknown. The role of associated factors such as the limb immobilization technique and genetics has been reported in the development of this complication, but, so far, there is no information regarding the effect of trauma severity on the risk of RSD occurrence. OBJECTIVES: Given the importance of diagnosing and treating this condition, we aimed to study the effect of trauma severity on the prevalence of RSD. PATIENTS AND METHODS: In this cross-sectional study, we examined patients with distal tibial fracture who visited Rasht Poursina hospital from 2010 to 2013. Exclusion criteria included associated fractures, underlying musculoskeletal diseases and mental and cognitive problems. To assess the severity of the initial injury in patients, the Hannover Fracture Scale 98 (HFS98) scoring checklist was used. The diagnosis of RSD was made on the basis of the IASP criterion. Demographic data, HFS98 scores, and information regarding RSD prevalence were analyzed using SPSS version 20. The Mann Whitney U nonparametric test was used for variables that were not normally distributed; the chi-square test was used to compare the qualitative variables. RESULTS: Among the 488 patients, 292 (59.83%) were male. The mean age of the study population was 44 ± 9.82 years. During the 6-month follow-up, RSD occurred in 45 patients, of whom 28 (62.22%) were female and 17 (37.77%) were male; there was thus a significant difference in the prevalence of RSD in terms of gender (P = 0.00; chi square test). The mean HFS98 score in patients without and with RSD was 3.081 ± 4.083 and 4.080 ± 4.622, respectively, and the difference was not statistically significant (P = 0.363; Mann Whitney U test). Analyses of the eight items of HFS98 shows that local circulation in patients with RSD is significantly better than that in patients without RDS (0.683 ± 0.822 vs. 0.528 ± 0.629, respectively). Statistical analysis showed that the odds ratio for RSD for patients with HFS95 score > 0 was 1.079 (confidence interval [CI]: 0.898 - 1.333). Moreover, the odds ratio for RSD was 1.100 (CI: 795 - 1.531) in patients with an injury severity score higher than the calculated mean score in patients without RSD (> 4.083). CONCLUSIONS: The results suggest no significant relationship between the severity of injury and risk of RSD occurrence, although the mean injury severity score was higher in patients with RSD than in those without RSD in this study population. The lower score of local circulation in patients with RSD than in those without RSD is a statistically significant finding and can be attributed to changes in the antioxidant levels at the injury site, which is one of the main mechanisms for the onset of RSD. Wound contamination was also justifiably higher in patients with RSD, although the difference was not statistically significant. In summary, the severity of injury alone cannot be a determining factor for predicting the probability of RSD.

The Effects of Nitroglycerine on Pain Control During the Propofol Injection; a Controlled, Double-Blinded, Randomized Clinical Trial.

BACKGROUND: The use of Propofol often results in pain upon injection, which is sometimes very distressing for patients. Many patients report some degree of pain or discomfort on injection with propofol. Injection-induced pain during induction of anesthesia can result in patient's discomfort. OBJECTIVES: This study was performed to evaluate the effects of nitroglycerine on pain severity in patients undergoing propofol injection. PATIENTS AND METHODS: In this double-blind randomized clinical trial, 100 patients with ASA class I and II undergoing anesthesia with propofol injection were selected for the study from 2012 to 2013 in Imam Reza training hospital. Patients were randomly assigned to case and control groups and received either 20 µg of nitroglycerine or normal saline as placebo. The severity of injection pain was assessed using a four-point scale. An anesthesiologist observed hemodynamic and local adverse effects. RESULTS: The pain severity in nitroglycerine group was significantly lower compared with the placebo group (P < 0.0001). Moreover, the local adverse reactions were observed only in three patients in the placebo group while no patient in the drug group experienced adverse effects (P = 0.242). The systolic blood pressure showed no significant difference between two groups before and after the induction of anesthesia but the diastolic blood pressure and the heart rate was significantly different between study groups. CONCLUSIONS: Nitroglycerine may be a safe and effective adjuvant therapeutic for pain reduction in patients under propofol injection. Hence, its use for reduction of propofol injection-induced pain is recommended.

Down-regulation of microRNA-26a and up-regulation of microRNA-27a contributes to aggressive progression of human osteosarcoma.

BACKGROUND: Osteosarcoma is the most common primary bone malignancy with high local aggressiveness and rapid metastasizing potential, resulting in poor survival. Increasing reports suggest that deregulated microRNAs (miRNAs) might provide novel therapeutic targets for cancers. However, the expression of miR-26a and miR-27a in osteosarcoma need further investigation in clinical samples. In our study, we evaluate the expression of these miRNAs in osteosarcoma tissues and compared with paired adjacent non-tumor bone tissues using RT-qPCR. METHODS: Total RNA was purified from patients with osteosarcoma and noncancerous bone tissues. Real-time PCR was applied to quantify the expression level of miR-26a and miR-27a. Moreover, the correlation of these markers with clinicopathological characteristics was also evaluated in osteosarcoma patients. A cox proportional hazards model was performed to assess multivariate analyses of prognostic values. RESULTS: Our result suggested that miR-26aexpression level in osteosarcoma bone tissue was significantly lower than that in the paired noncancerous bone tissues. MiR-27a expression was higher in osteosarcoma bone tissue in comparison with paired noncancerous bone tissues. The results indicated that low expression level of miR-26a and high expression of miR-27a were associated with high TNM stage (P = 0.001; P = 0.012), tumor grade (P = 0.007; P = 0.016), and distant metastasis (P = 0.004; P = 0.001). Kaplan-Meier analysis and log-rank test indicated that patients with low expression of miR-26a and high expression of miR-27a had shorter overall survival (log-rank test: P < 0.001). Multivariate Cox proportional hazards model analysis showed that low expression of miR-26a and high expression of miR-27a (P = 0.021; P = 0.011), high TNM stage (P = 0.001; P = 0.003), tumor grade (P = 0.005; P = 0.01), and distant metastasis.(P = 0.002; P = 0.005) were independent prognostic factors for overall survival patients with osteosarcoma cancer. CONCLUSIONS: In conclusion, our findings suggested that expression level of miR-26a and miR-27a contributes to aggressive progression of this malignancy. Therefore, may have clinical potentials as a non-invasive diagnostic/prognostic biomarker for osteosarcoma patients.