Osteosarcoma is an aggressive bone tumor with high resistance to radiotherapy. Pleckstrin homology-like domain family A member 2 (PHLDA2) displays low expression in human osteosarcoma as a proapoptosis factor. miRNAs have been shown to be important in modulating translation and therapeutic responsiveness in solid tumors. Herein, we used luciferase assay to show that miR-214 downregulates the PHLDA2 expression by targeting its 3′-untranslated region (UTR). A high level of miR-214 was identified in tumor tissues from 30 osteosarcoma patients via qPCR analysis, associated positively with lung metastasis. Ectopic expression miR-214 enhanced radioresistance in osteosarcoma cells, with decreased IR-induced apoptosis. Moreover, the depletion of miR-214 enhanced radiosensitivity in both osteosarcoma cells and mouse xenograft models. Importantly, we showed that miR-214 regulated the activation of phosphatidylinositol-3-kinase/Akt signaling pathway by inhibiting PHLDA2. Finally, the introduction of PHLDA2 cDNA lacking the 3′-UTR or treatment with Akt inhibitor LY294002 partially abrogated miR-214-induced radioresistance. In summary, our results reveal that the upregulation of miR-214 as a frequent event in osteosarcoma contributes to radioresistance by regulating the PHLDA2/Akt pathway. The miR-214/PHLDA2/Akt axis provides a new avenue toward understanding the mechanism of radiosensitivity and may be a potential target for osteosarcoma intervention.
Background: Ulnar impaction syndrome caused by positive ulnar variance often requires ulnar shortening osteotomy (USO) to unload the ulnocarpal joint. The therapeutic effect of USO in treatment of ulnar impaction syndrome is limited due to complications such as hardware irritation, non-union rotation and angulation. Despite various devices have been introduced to overcome these limitations, more accurate and simple devices are still needed. The purpose of this study was to introduce a novel method of the ortho-bridge fixation system combined with 3D-printed guide plate to achieve precise ulnar shortening osteotomy with less complications simply. Methods: This was a retrospective study comprising nine patients with ulnar impaction syndrome who underwent ulnar shortening osteotomy by this method. The CT scan data of patients were retrieved for printing the osteotomy guide plate. The ortho-bridge system served as ulnar shortening and internal fixation. The outcome measurements included the time to union, complications, range of motion, grip strength and wrist pain. Results: The ulna was shortened successfully in all of the nine cases without rotation and angulation. Non-union was not observed in any of the cases during follow-up between 12 months after surgery. The range of motion, grip strength and wrist pain also improved following surgery (p<0.05). Conclusion: The ortho-bridge internal fixation system combined with 3D-printed osteotomy guide effectively simplified the procedure, and restored ulnar variance without rotation, angulation and non-union. It is a reliable method for treating ulnocarpal impaction syndrome through ulnar shortening osteotomy.
Background: The size and versatility of anterolateral thigh (ALT) flap enables a bi-paddle flap to cover complex and extensive defects optimally. However, it is characterized by variations in the sources of blood vessels and in the number of perforators, which increases the chances of failure of harvesting a bi-paddle flap. We present our method to overcome such failure. This is the first study exploring the optimal salvaging algorithm to overcome harvesting failure with the bi-paddle ALT flap.Methods: From January 2014 to December 2020, in 9 patients to be treated with bi-paddle ALT flap for soft-tissue defects (range, 48-288 cm 2 ), there was failure of flap harvest because of perforator variations. We redesigned and converted the flaps to other forms for harvest intraoperatively, based on the characteristics of the defect, and the number and sources of perforators.Results: Salvage of flap harvest was successfully performed in all 9 cases. In 4 cases the flap with a single perforator was converted to widened-single-perforator flaps; in 2 cases, a single perforator was converted to a de-epithelialized flap; in 2 cases of 2 perforators from different main branches, conversion was to sequential chimeric flaps; in the remaining case of 2 perforators from the descending branch and transverse branch, conversion was to a combined transverse-and-descending branches flap. Venous compromise occurred in only 1 case, and the patient survived after revised surgery. Local infection in the receiving area occurred in 3 cases, and was cured by wound dressing. All flaps survived (follow-up 5-24 months).Conclusions: Despite preoperative preparation, anatomic variations resulted in failure of bi-paddle ALT flap harvesting. As shown by our results, it is feasible to redesign and convert the bi-paddle flap to other forms based on the defect characteristics, and the number and sources of perforators.
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