Association of Preoperative Plasma D-Dimer and Fibrinogen and Osteosarcoma Outcome.

Objective: We aimed to evaluate the utility of preoperative D-dimer and plasma fibrinogen (PF) levels as useful markers for predicting the clinical value of patients with osteosarcoma. Methods: 145 enrolled patients with osteosarcoma were studied retrospectively. We determined the critical values of D-dimer and PF by receiver operating characteristic curve analysis. Cox regression analysis was used to assess prognostic role of the D-dimer and PF levels among osteosarcoma patients. Results: The critical values of D-dimer and PF were calculated to be 0.46 µg/mL and 3.34 mg/mL, respectively. Upregulation of D-dimer and PF showed positive correlations with a higher clinical stage, tumour metastasis and recurrence. Survival curve results confirmed that osteosarcoma patients with higher levels of D-dimer and PF predicted worse overall survival (OS) and progression-free survival (PFS). Moreover, only a high D-dimer level was associated with a shorter OS (P = 0.013) and PFS (P = 0.042) in both the univariate and multivariate analysis. Conclusion: Elevated preoperative D-dimer levels are correlated with aggressive clinicopathological features and poor survival outcomes, which indicates that assessment of the D-dimer could be a useful prognostic marker in osteosarcoma.

Role of autophagy in drug resistance and regulation of osteosarcoma (Review).

Osteosarcoma (OS) is a malignant tumor originating from primitive mesenchymal tissue that occurs mostly in children and adolescents. It is the most common type of malignant tumor originating from bone. The combination of chemotherapy and surgery is an important treatment strategy for OS; however, multidrug resistance frequently leads to failure of chemotherapy for OS. Autophagy is considered an important mechanism through which bone tumor cells escape apoptosis; inhibition of autophagy may significantly increase the sensitivity of tumor cells to chemotherapeutic drugs. The present review discusses the relationship between chemotherapy resistance and autophagy-related genes, the regulation of autophagy in OS, as well as drugs that inhibit protective autophagy in tumors or cause autophagic death of OS cells or increase their sensitivity to chemotherapy drugs, thereby reducing chemotherapy resistance and increasing efficacy.

[Corrigendum] Silencing of RIPK4 inhibits epithelial­mesenchymal transition by inactivating the Wnt/ß­catenin signaling pathway in osteosarcoma.

Subsequently to the publication of the above article, the authors have realized that the same western blotting data shown for the vimentin bands for the U2OS cell line in Fig. 3B on p. 1159 had inadvertently been re­used for the ß­catenin bands for the U2OS cell line in Fig. 5A on p. 1161. The authors have re­examined their original data, and have realized that Fig. 5 was assembled incorrectly. The corrected version of Fig. 5, showing the correct ß­catenin bands for the U2OS cell line, is shown opposite. Note that this error did not quantitatively affect either the results or the overall conclusions reported in this paper. The authors are grateful to the Editor of Molecular Medicine Reports for allowing them this opportunity to publish a Corrigendum, and they apologize to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 21: 1154­1162, 2020; DOI: 10.3892/mmr.2020.10939].

[Case control study on T-plate combined with suture anchors for the treatment of Neer â ¡b clavicle fractures].

OBJECTIVE: To compare the clinical efficacy of distal radius T-plate combined with suture anchor and distal clavicle anatomical locking plate combined with suture anchor in the treatment of Neer Ⅱb distal clavicle fracture. METHODS: From June 2014 to June 2018, 42 patients with Neer Ⅱb distal clavicle fractures were retrospectively analyzed. According to different surgical methods, they were divided into the observation group (T-shaped plate combined with suture anchor) and the control group (anatomical locking plate combined with suture anchor). There were 22 patients in the observation group and 20 patients in the control group. In the observation group, there were 13 males and 9 females, aged from 22 to 70 (45.78± 14.44) years old, 12 cases on the left side and 10 cases on the right side, 8 cases of traffic accident injury and 14 cases of fall. In the control group, there were 12 males and 8 females, aged from 24 to 66 (44.17±15.58) years, 13 cases on the left side and 7 cases on the right side, 6 cases of traffic accident injuryand 14 cases of fall. The operation time, intraoperative blood loss and fracture healing time were compared between the two groups, and Constant Murley score was used to evaluate shoulder joint function. RESULTS: The patients in both groups were followed up for 18 to 24 (20.96±2.02) months. The incisions of both groups were healed at stageⅠ. The fracture ends of both groups were bony healed at the last follow up. There was no significant difference in operation time, intraoperative blood loss and fracture healing time between two groups (P>0.05);there was no significant difference in shoulder joint function between two groups at 3 months after operation (P>0.05). CONCLUSION: The two methods can obtain satisfactory results in the treatment of Neer Ⅱb distal clavicle fractures, especially suitable for patients with comminuted distal clavicle fractures or osteoporosis; the clinical effect of the treatment of NeerⅡb distal clavicle fractures with T type distal radius plate combined with suture anchor is satisfactory, which provides another feasible treatment scheme for clinic.

The prevalence and risk factors of acute kidney injury in patients undergoing hip fracture surgery: a meta-analysis.

Acute kidney injury (AKI) was a frequent complication following hip fracture surgery, but recent studies reported inconsistent findings. Our study was aimed at clarifying the prevalence and risk factors of AKI after hip fracture surgery. Pubmed, Embase, and Web of Science were systematically searched from the inception to March 2020 to identify observational studies investigating the prevalence and risk factors of AKI in patients undergoing hip fracture surgery. Pooled prevalence and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using a random-effects model. Publication bias was evaluated with a funnel plot and statistical test. All the statistical analyses were performed using Stata version 12.0. A total of 11 studies with 16,421 patients was included in the current meta-analysis. The pooled prevalence of AKI in patients undergoing hip fracture surgery was 17% (95%CI, 14%-21%) with substantial heterogeneity (I2 = 95%). Postoperative serum albumin (OR 1.80; 95%CI, 1.38-2.36) was a significant predictor for AKI. Age (OR 1.01; 95%CI, 0.95-1.07) and ACE inhibitors (OR 1.38; 95%CI, 0.92-2.07) were associated with increased the risk of AKI, but the results were not statistically significant. No significant publication bias was identified through statistical tests (Egger's test, p = 0.258 and Begg's test, p = 0.087). In conclusion, our findings indicated that the pooled AKI following hip fracture surgery was approximately 17%. Postoperative serum albumin was a potential significant risk factor for AKI.

Research progress regarding the role of long non-coding RNAs in osteosarcoma.

Osteosarcoma is a malignant tumor that occurs in children and adolescents. Although treatments for osteosarcoma have improved, the likelihood of survival remains low for most patients with metastasis and recurrence. Elucidating the mechanism underlying the development of osteosarcoma and chemotherapy resistance will be important to improve diagnosis and treatment. Long non-coding RNAs (lncRNAs), which are longer than 200 nucleotides in length and do not encode for proteins, have been shown to play a regulatory role in the occurrence and development of osteosarcoma, and are expected to serve as biomarkers and molecular targets. This review discusses the progress in the study of the role of lncRNAs in osteosarcoma, and highlights the recent developments in this field.

Silencing of RIPK4 inhibits epithelial­mesenchymal transition by inactivating the Wnt/ß­catenin signaling pathway in osteosarcoma.

Receptor interacting protein kinase 4 (RIPK4) is a serine/threonine kinase that plays an important role in the regulation of cell proliferation, invasion and metastasis in several malignancies; however, its clinical significance and biological function in osteosarcoma (OS) remains unknown. In the present study, the RIPK4 expression level was significantly upregulated in OS tissues and cell lines. High RIPK4 expression was positively associated with larger sized tumors, advanced Enneking stage and poor prognosis in patients with OS. Furthermore, the results revealed that RIPK4 knockdown in the OS cell lines MG­63 and U2OS reduced cell migration and invasion via the inhibition of epithelial­mesenchymal transition (EMT) process, whereby E­cadherin expression was increased and N­cadherin and vimentin expression decreased. Mechanistically, RIPK4 knockdown inhibited EMT by inactivating the Wnt/ß­catenin signaling pathway. These findings suggest that RIPK4 may be a novel potential therapeutic target for the treatment of metastases in patients with OS.

WNT5A promotes migration and invasion of human osteosarcoma cells via SRC/ERK/MMP-14 pathway.

WNT5A, a representative ligand of activating several non-canonical WNT signal pathways, plays significant roles in oncogenesis and tumor inhibition. It has been shown that the non-receptor tyrosine kinase SRC is required for WNT5A-induced invasion of osteosarcoma cells. However, the precise molecular mechanism underlying WNT5A/SRC-mediated osteosarcoma cells invasion remains poorly defined. The study was designed to explore the role of ERK1/2 in WNT5A/SRC-induced osteosarcoma cells invasion and the downstream target of the SRC/ERK1/2 signalings. We found that WNT5A (100 ng/mL) remarkably stimulated migration and invasion of human osteosarcoma MG-63 cells, whereas inhibiting either SRC kinase activity by siRNA-mediated SRC silence or ERK1/2 phosphorylation by PD98059 treatment suppressed these effects, which suggested that the activation of SRC and ERK1/2 is essential for WNT5A-induced MG-63 cells migration and invasion. Furthermore, ERK1/2 phosphorylation induced by WNT5A was dramatically blocked by SRC siRNA. Additionally, our study further demonstrated that MMP-14 was upregulated after exposure to WNT5A in MG-63 cells, and the increased expression was blocked by SRC siRNA or PD98059. Collectively, these results indicate that WNT5A activates SRC/ERK1/2 signal pathway, leading to the upregulation of MMP-14 expression and MG-63 cells migration and invasion.