[Effectiveness analysis of surgical treatment of Schatzker type â £ tibial plateau fractures].

Objective: To introduce a surgical protocol based on the location and orientation of the apex of the medial condylar fracture line for the treatment of Schatzker type Ⅳ tibial plateau fractures and report the preliminary effectiveness. Methods: The clinical data of 18 patients with Schatzker type Ⅳ tibial plateau fractures underwent open reduction and internal fixation between March 2012 and April 2016 were retrospectively analysed. There were 6 males and 12 females, aged 36-74 years (mean, 45 years). The causes of injury included traffic accident in 2 cases, falling in 14 cases, bruise injury in 1 case, and crush injury of heavy object in 1 case. All cases were fresh closed fractures, without injury of nerves and blood vessels. According to sub type of Wahlquist tibial plateau type Ⅳ fracture classification, there were 1 case of type A, 5 cases of type B, and 12 cases of type C. The interval of injury and operation was 6-16 days (mean, 9.5 days). The location of the apex of the medial condylar fracture line was determined the surgical approach. After operation, reduction of tibial plateau fractures was evaluated by the DeCoster score evaluation criteria. The knee joint function was assessed by short Musculoskeletal Function Assessment (SMFA) score and Hospital for Special Surgery (HSS) score. Results: The incisions all healed by first intension after operation without surgery related complications. All the patients obtained satisfactory exposure and reduction during operation. According to DeCoster score evaluation criteria, the results were excellent in 13 cases and fair in 5 cases. All the patients were followed up 12-30 months (mean, 18 months). X-ray films showed that all fractures healed at 10-16 weeks (mean, 12 weeks) after operation. There was no plate displacement, screw loosening, and other complications occurred during follow-up. At last follow-up, the SMFA score was 15-48 (mean, 28.5). The HSS score was 52-94 (mean, 81.1), and the results were excellent in 10 cases, good in 5 cases, fair in 2 cases, and poor in 1 case with an excellent and good rate of 83.3%; the main clinical manifestation was severe traumatic osteoarthritis symptom in 1 case with the fair result. Conclusion: The surgical program should be developed based on the location and orientation of the apex of the medial condylar fracture line. Open reduction and internal fixation for treating Schatzker type Ⅳ fractures can achieve satisfactory effectiveness.

Poly(lactic-co-glycolic acid) nanoparticles conjugated with CD133 aptamers for targeted salinomycin delivery to CD133+ osteosarcoma cancer stem cells.

BACKGROUND: Cancer stem cells (CSCs) possess the characteristics associated with normal stem cells and are responsible for cancer initiation, recurrence, and metastasis. CD133 is regarded as a CSCs marker of osteosarcoma, which is the most common primary bone malignancy in childhood and adolescence. Salinomycin, a polyether ionophore antibiotic, has been shown to kill various CSCs, including osteosarcoma CSCs. However, salinomycin displayed poor aqueous solubility that hinders its clinical application. The objective of this study was to develop salinomycin-loaded nanoparticles to eliminate CD133(+) osteosarcoma CSCs. METHODS: The salinomycin-loaded PEGylated poly(lactic-co-glycolic acid) nanoparticles (SAL-NP) conjugated with CD133 aptamers (Ap-SAL-NP) were developed by an emulsion/solvent evaporation method, and the targeting and cytotoxicity of Ap-SAL-NP to CD133(+) osteosarcoma CSCs were evaluated. RESULTS: The nanoparticles are of desired particle size (~150 nm), drug encapsulation efficiency (~50%), and drug release profile. After 48 hours treatment of the Saos-2 CD133(+) osteosarcoma cells with drugs formulated in Ap-SAL-NP, SAL-NP, and salinomycin, the concentrations needed to kill 50% of the incubated cells were found to be 2.18, 10.72, and 5.07 µg/mL, respectively, suggesting that Ap-SAL-NP could be 4.92 or 2.33 fold more effective than SAL-NP or salinomycin, respectively. In contrast, Ap-SAL-NP was as effective as SAL-NP, and less effective than salinomycin in Saos-2 CD133(-) cells, suggesting that Ap-SAL-NP possess specific cytotoxicity toward Saos-2 CD133(+) cells. Ap-SAL-NP showed the best therapeutic effect in Saos-2 osteosarcoma xenograft mice, compared with SAL-NP or salinomycin. Significantly, Ap-SAL-NP could selectively kill CD133(+) osteosarcoma CSCs both in vitro and in vivo, as reflected by the tumorsphere formation and proportion of Saos-2 CD133(+) cells. CONCLUSION: Our results suggest that CD133 is a potential target for drug delivery to osteosarcoma CSCs and that it is possible to significantly inhibit the osteosarcoma growth by killing CD133(+) osteosarcoma CSCs. We demonstrated that Ap-SAL-NP have the potential to target and kill CD133(+) osteosarcoma CSCs.

Wogonin protects rat dorsal root ganglion neurons against tunicamycin-induced ER stress through the PERK-eIF2α-ATF4 signaling pathway.

Endoplasmic reticulum (ER) stress has been demonstrated to contribute to neurodegeneration in multiple nervous system diseases. Wogonin is a flavonoid isolated from Scutellaria baicalensis root and has multiple pharmacological effects, including anti-inflammatory, antioxidant, and anticancer effects. It has a protective role in nervous system diseases; however, the pharmacological function of wogonin in the spinal cord is still with limited acquaintance. In the present study, rat dorsal root ganglion (DRG) neurons were pretreated with different concentrations of wogonin (0-100 µM) before inducing ER stress using tunicamycin (TUN) (0.75 µg/ml). Wogonin pretreatment at 75 and 100 µM had a cytoprotective effect on cells against TUN-induced toxicity. Wogonin also decreased the number of the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive DRG neurons and increased expression of superoxide dismutase (SOD), which was accompanied by decreased malondialdehyde (MDA) level. The induction of apoptosis was prevented with reduction in expression level of Bax and concomitant increase in B cell lymphoma 2 (Bcl-2) level. Furthermore, wogonin downregulated expression level of ER stress genes coding for glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), active caspase 12, transcription factor 4 (ATF4), and phosphorylation of pancreatic ER stress kinase (PERK) and eukaryotic initiation factor 2 alpha (eIF2α). The current study indicated that wogonin modulated stress-responsive genes, helping DRG neurons prevent TUN-induced ER stress through the PERK-eIF2α-ATF4 signaling pathway.