Comparative Biomechanical Analysis of Anterior Process Locking Plate Alone versus Combined with Percutaneous Cannulated Screw Fixation for Sanders Type II Calcaneal Fractures: A Finite Element Study.

BACKGROUND Calcaneal fractures are the most common tarsal bone fractures, and account for 75% of intra-articular fractures. The purpose of this study was to compare the biomechanical stability of the anterior process locking plate combined with the percutaneous cannulated screw fixation (screw group) versus the anterior process locking plate fixation alone (plate group) for the treatment of Sanders type II calcaneal fractures using finite element analysis to provide a theoretical basis for clinical work. MATERIAL AND METHODS We established a 3D model of Sanders type II calcaneal fracture; assigned material properties to the internal fixation systems; applied loads; set up analysis criteria; analyzed the displacement of the fracture, relative displacement, stress state of bone tissue, and internal fixation; and compared mechanical stability. RESULTS For Sanders type II A, II B, and II C calcaneal fractures, the degree of displacement and relative displacement of the fracture in the screw group was less than that of the plate group. For all subtypes of Sanders type II calcaneal fractures, the screw group had better mechanical stability than the plate group. CONCLUSIONS Both fixation methods (screw and plate group) were within a reasonable range for restoring the levelling effect of the joint surface and maintaining the strength of fixation, and both had good mechanical stability. Finite element analysis is a relatively reliable method, and biomechanics and clinical studies must further verify the experimental results.

Directly targeting glutathione peroxidase 4 may be more effective than disrupting glutathione on ferroptosis-based cancer therapy.

BACKGROUND: Cancer is one of the major threats to human health and current cancer therapies have been unsuccessful in eradicating it. Ferroptosis is characterized by iron-dependence and lipid hydroperoxides accumulation, and its primary mechanism involves the suppression of system Xc--GSH (glutathione)-GPX4 (glutathione peroxidase 4) axis. Co-incidentally, cancer cells are also metabolically characterized by iron addiction and ROS tolerance, which makes them vulnerable to ferroptosis. This may provide a new tactic for cancer therapy. SCOPE OF REVIEW: The general features and mechanisms of ferroptosis, and the basis that makes cancer cells vulnerable to ferroptosis are described. Further, we emphatically discussed that disrupting GSH may not be ideal for triggering ferroptosis of cancer cells in vivo, but directly inhibiting GPX4 and its compensatory members could be more effective. Finally, the various approaches to directly inhibit GPX4 without disturbing GSH were described. MAJOR CONCLUSIONS: Targeting system Xc- or GSH may not effectively trigger cancer cells' ferroptosis in vivo the existence of other compensatory pathways. However, directly targeting GPX4 and its compensatory members without disrupting GSH may be more effective to induce ferroptosis in cancer cells in vivo, as GPX4 is essential in preventing ferroptosis. GENERAL SIGNIFICANCE: Cancer is a severe threat to human health. Ferroptosis-based cancer therapy strategies are promising, but how to effectively induce ferroptosis in cancer cells in vivo is still a question without clear answers. Thus, the viewpoints raised in this review may provide some references and different perspectives for researchers working on ferroptosis-based cancer therapy.

Safety of exposure to high static magnetic fields (2 T-12 T): a study on mice.

OBJECTIVES: We aimed to evaluate the biological effects of high static magnetic field (HiSMF, 2-12 Tesla [T]) exposure on mice in a stable and effective breeding environment in the chamber of a superconducting magnet. METHODS: C57BL/6 mice were bred in the geomagnetic field and HiSMF with different magnetic field strengths (2-4 T, 6-8 T, and 10-12 T) for 28 days. The body weight, blood indices, organ coefficients, and histomorphology of major organs were analyzed. RESULTS: The results showed that the HiSMF had no significant effect on the body weight, organ coefficients, or histomorphology of major organs in mice. The HiSMF had no effect on most routine blood and biochemical indices, but the value of the mean corpuscular hemoglobin (MCH) was increased in the 2-4 T group compared with that of the other groups, and the uric acid level (UA) was decreased in the three HiSMF groups compared with that of the control group. CONCLUSION: The C57BL/6 mice were not affected when they were exposed to different HiSMF environments for 28 days. KEY POINTS: • No physiological problems were observed in mice with long-term whole-body exposure to HiSMF.

Effectiveness of biceps tenodesis versus SLAP repair for surgical treatment of isolated SLAP lesions: A systemic review and meta-analysis.

BACKGROUND: Type II superior labrum anterior and posterior (SLAP) lesions could induce chronic shoulder pain and impaired movement. Current management of Type II SLAP lesions consists of two well-established surgical procedures: arthroscopic biceps tenodesis and SLAP repair. However, which technique is preferred over the other is still a controversy. METHODS: We performed a systematic electronic database search on Cochrane Central Register of Controlled Trials, MEDLINE and Embase to identify articles equating superior labral repair with biceps tenodesis, which were reported before August 2017 which included the phrase "superior labral anterior posterior" or "SLAP." The randomised controlled clinical trials that met our criteria were evaluated for quality of methodology. The results obtained were further analysed and correlated to present the benefits and drawbacks comparing the two SLAP repair surgical procedures. RESULT: Based on our inclusion and exclusion criteria, we identified five articles (204 patients) that were included in this meta-analysis. The results indicate that prevalence of patients return to preinjury sports level and the patients satisfaction were found to be significantly better in tenodesis group than in the SLAP repair group (p < 0.05). As for the patient age, VAS score, American Shoulder and Elbow Surgeons score, University of California at Los Angeles score, postoperative stiffness and reoperation rates, no significant differences were evident among the two groups, thus supporting the results reported in the current literatures (p > 0.05). CONCLUSIONS: Both the surgical treatments, SLAP repair and the biceps tenodesis, are efficacious in pain alleviation and recovery of shoulder function. But, compared with SLAP repair, biceps tenodesis showed higher rate of patient satisfaction and return to preinjury sports participation. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Impart better understanding regarding discrepancies in the outcomes between biceps tenodesis and SLAP repair in treating patients with isolated Type II SLAP lesions.

Tumor cell-targeted delivery of CRISPR/Cas9 by aptamer-functionalized lipopolymer for therapeutic genome editing of VEGFA in osteosarcoma.

Osteosarcoma (OS) is a highly aggressive pediatric cancer, characterized by frequent lung metastasis and pathologic bone destruction. Vascular endothelial growth factor A (VEGFA), highly expressed in OS, not only contributes to angiogenesis within the tumor microenvironment via paracrine stimulation of vascular endothelial cells, but also acts as an autocrine survival factor for tumor cell themselves, thus making it a promising therapeutic target for OS. CRISPR/Cas9 is a versatile genome editing technology and holds tremendous promise for cancer treatment. However, a major bottleneck to achieve the therapeutic potential of the CRISPR/Cas9 is the lack of in vivo tumor-targeted delivery systems. Here, we screened an OS cell-specific aptamer (LC09) and developed a LC09-functionalized PEG-PEI-Cholesterol (PPC) lipopolymer encapsulating CRISPR/Cas9 plasmids encoding VEGFA gRNA and Cas9. Our results demonstrated that LC09 facilitated selective distribution of CRISPR/Cas9 in both orthotopic OS and lung metastasis, leading to effective VEGFA genome editing in tumor, decreased VEGFA expression and secretion, inhibited orthotopic OS malignancy and lung metastasis, as well as reduced angiogenesis and bone lesion with no detectable toxicity. The delivery system simultaneously restrained autocrine and paracrine VEGFA signaling in tumor cells and could facilitate translating CRISPR-Cas9 into clinical cancer treatment.

Potential Diagnostic and Therapeutic Applications of Oligonucleotide Aptamers in Breast Cancer.

Breast cancer is one of the most common causes of cancer related deaths in women. Currently, with the development of early detection, increased social awareness and kinds of treatment options, survival rate has improved in nearly every type of breast cancer patients. However, about one third patients still have increased chances of recurrence within five years and the five-year relative survival rate in patients with metastasis is less than 30%. Breast cancer contains multiple subtypes. Each subtype could cause distinct clinical outcomes and systemic interventions. Thereby, new targeted therapies are of particular importance to solve this major clinical problem. Aptamers, often termed "chemical antibodies", are functionally similar to antibodies and have demonstrated their superiority of recognizing target with high selectivity, affinity and stability. With these intrinsic properties, aptamers have been widely studied in cancer biology and some are in clinical trials. In this review, we will firstly discuss about the global impacts and mechanisms of breast cancer, then briefly highlight applications of aptamers that have been developed for breast cancer and finally summarize various challenges in clinical translation of aptamers.

Osteoclastic miR-214 targets TRAF3 to contribute to osteolytic bone metastasis of breast cancer.

The role of osteoclastic miRNAs in regulating osteolytic bone metastasis (OBM) of breast cancer is still underexplored. Here, we examined the expression profiles of osteoclastogenic miRNAs in human bone specimens and identified that miR-214-3p was significantly upregulated in breast cancer patients with OBM. Consistently, we found increased miR-214-3p within osteoclasts, which was associated with the elevated bone resorption, during the development of OBM in human breast cancer xenografted nude mice (BCX). Furthermore, genetic ablation of osteoclastic miR-214-3p in nude mice prevent the development of OBM. Conditioned medium from MDA-MB-231 cells dramatically stimulated miR-214-3p expression to promote osteoclast differentiation. Mechanistically, a series of in vitro study showed that miR-214-3p directly targeted Traf3 to promote osteoclast activity and bone-resorbing activity. In addition, osteoclast-specific miR-214-3p knock-in mice showed remarkably increased bone resorption when compared to the littermate controls, which was attenuated after osteoclast-targeted treatment with Traf3 3'UTR-containing plasmid. In BCX nude mice, osteoclast-targeted antagomir-214-3p delivery could recover the TRAF3 protein expression and attenuate the development of OBM, respectively. Collectively, inhibition of osteoclastic miR-214-3p may be a potential therapeutic strategy for breast cancer patients with OBM. Meanwhile, the intraosseous TRAF3 could be a promising biomarker for evaluation of the treatment response of antagomir-214-3p.

Present Advances and Future Perspectives of Molecular Targeted Therapy for Osteosarcoma.

Osteosarcoma (OS) is a bone cancer mostly occurring in pediatric population. Current treatment regime of surgery and intensive chemotherapy could cure about 60%-75% patients with primary osteosarcoma, however only 15% to 30% can be cured when pulmonary metastasis or relapse has taken place. Hence, novel precise OS-targeting therapies are being developed with the hope of addressing this issue. This review summarizes the current development of molecular mechanisms and targets for osteosarcoma. Therapies that target these mechanisms with updated information on clinical trials are also reviewed. Meanwhile, we further discuss novel therapeutic targets and OS-targeting drug delivery systems. In conclusion, a full insight in OS pathogenesis and OS-targeting strategies would help us explore novel targeted therapies for metastatic osteosarcoma.

Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation.

Emerging evidence indicates that osteoclasts direct osteoblastic bone formation. MicroRNAs (miRNAs) have a crucial role in regulating osteoclast and osteoblast function. However, whether miRNAs mediate osteoclast-directed osteoblastic bone formation is mostly unknown. Here, we show that increased osteoclastic miR-214-3p associates with both elevated serum exosomal miR-214-3p and reduced bone formation in elderly women with fractures and in ovariectomized (OVX) mice. Osteoclast-specific miR-214-3p knock-in mice have elevated serum exosomal miR-214-3p and reduced bone formation that is rescued by osteoclast-targeted antagomir-214-3p treatment. We further demonstrate that osteoclast-derived exosomal miR-214-3p is transferred to osteoblasts to inhibit osteoblast activity in vitro and reduce bone formation in vivo. Moreover, osteoclast-targeted miR-214-3p inhibition promotes bone formation in ageing OVX mice. Collectively, our results suggest that osteoclast-derived exosomal miR-214-3p transfers to osteoblasts to inhibit bone formation. Inhibition of miR-214-3p in osteoclasts may be a strategy for treating skeletal disorders involving a reduction in bone formation.

[Effect of supplementing qi, blood-activating and kidney-nourishing therapy on postoperative recovery in patients with lumber disc herniation].

OBJECTIVE: To investigate the effect of supplementing qi, activating blood circulation and tonifying kidney therapy on the postoperative outcomes of patients undergoing lumber intervertebral disc herniation. METHODS: From January 2010 to May 2012, 120 patients with lumbar intervertebral disc herniation undergoing surgical treatment in Nanfang hospital were randomized into two equal groups to receive routine therapy (control group) and additional treatment with Yiqi Houxue Bushen Decoction (treatment group). The effect of the interventions was evaluated by assessing the Visual Analogue Scale(VAS), Japanese Orthopedic Association Scores (JOA), WHO Quality of Life-BREF (WHOQOL-BREF), length of hospital stay and adverse event. RESULTS: All the 120 patients were followed up and analyzed. Significant differences were found between the treatment and control groups in VAS, JOA Scores, and WHOQOL-BREF (P<0.01) at 2, 4, and 8 week and at 6 and 12 months after the surgery. At 6 and 12 months postoperatively, the JOA Scores (P<0.01), but not the VAS and WHOQOL-BREF, differed significantly between the two groups. CONCLUSION: Blood-activating and kidney-nourishing therapy is effective in promoting postoperative recovery and helps reduce the clinical symptoms and minimize the adverse events in patients undergoing surgery for lumber intervertebral disc herniation.