A Novel Stepwise Technique for Safe and Effective Transoral Release of Irreducible Atlantoaxial Dislocation: A Retrospective Study of 201 Cases.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To verify the clinical efficacy of a novel transoral stepwise release technique (TSRT) for the treatment of irreducible atlantoaxial dislocations (IAAD). SUMMARY OF BACKGROUND DATA: Anterior release for IAAD remains challenging, with a 3.2 times higher complication rate than posterior release. However, there are some patients who cannot achieve successful reduction from a posterior approach and require the higher-risk anterior release. Our work presents a novel anterior release technique that aims to minimize iatrogenic injury and associated complications from an anterior release. MATERIALS AND METHODS: IAAD cases who were treated with TSRT were retrospectively studied. Primary outcomes included fusion rate, complications, and neurological function over the course of a minimum 1-year follow-up. Radiographic differences between preoperative and postoperative imaging were also considered. A preoperative prediction model for the actual release grade was developed using multivariate logistic regression based on demographic factors and the craniovertebral abnormalities identified on preoperative images, evaluating the need for higher-grade TSRT release. RESULTS: We included 201 IAAD cases, with 42% (84/201) demonstrating degeneration of the atlantoaxial joint or anterior-hook-like dens. The reduction was achieved in all cases, with 80% (160/201) of cases only requiring relatively low-grade or grade I types TSRT release. Degeneration of the atlantoaxial joint was significantly associated with the need for higher-grade TSRT release (odds ratio:16.68, CI: 2.91-94.54, P = 0.002). The overall complication rate was 4.5% (9/201). Over the course of follow-up, the fusion rate reached 98.5%, and the American Spinal Injury Association and Japanese Orthopedic Association scores were significantly improved to 97.28 and 16.25 ( P < 0.01 and P < 0.01), respectively. CONCLUSION: This study demonstrated that our novel TSRT anterior release technique demonstrated complication rates similar to those published in the literature for posterior release. TSRT can be used as an alternative to posterior release techniques for refractory cases or when a posterior approach is not considered viable.

Incidence and management of surgical site infection in the cervical spine following a transoral approach.

PURPOSE: Transoral approach can accomplish ventral decompression directly. However, surgical site infection (SSI) cannot be ignored. This paper aims to review the prevalence of infection and conduct advice for the treatment of SSI in the cervical spine following the transoral approach. METHODS: A retrospective analysis of patients with SSI after transoral atlantoaxial reduction plate (TARP) surgery was performed. SSI was classified into three kinds according to the modified American CDC criteria. RESULTS: 2.9% (17/581) patients who underwent TARP surgery, experienced SSI, of which five had superficial SSI (SI), eight had deep SSI (DI), and four had organ/space SSI (O/SI). The patients with SI underwent intravenous antibiotic treatment and were ultimately cured. Among the remaining 12 patients with DI and O/SI, 11 underwent reoperation for TARP system removal and subsequently one-stage posterior occipitocervical fixation, and one patient experienced infection two months post-operatively and died without receiving treatment. Among patients who underwent revision surgery, three experienced intracranial infection due to intra-operative dural tears, and continuous lumbar cerebrospinal fluid drainage and intrathecal injection of antibiotics were used as effective and appropriate treatments, with outcomes of one recovery and two deaths. All patients with SSI were begun on intravenous antibiotics with conversion to oral antibiotics. CONCLUSIONS: The incidence of SSI was 2.9% (17/581). Adequate peri-operative preparation, early diagnosis, and appropriate treatment of SSI require further research.

Prevertebral soft tissue swelling after anterior cervical internal fixation at different segments: a retrospective study.

Atlantoaxial segments have not been discussed in existing studies on prevertebral soft tissue (PVST) swelling after cervical operations. This study aimed to investigate the characteristics of PVST swelling after anterior cervical internal fixation at different segments. This retrospective study included patients who underwent transoral atlantoaxial reduction plate (TARP) internal fixation (Group I, n=73), C3/C4 anterior decompression and vertebral fixation (Group II, n=77), or C5/C6 anterior decompression and vertebral fixation (Group III, n=75) at our Hospital. The PVST thickness at C2, C3, and C4 segments was measured before and 3 days after the operation. Time of extubation, number of patients with postoperative re-intubation and dysphagia were collected. Results show that all patients had significant postoperative PVST thickening (all P<0.01). PVST thickening at C2, C3, and C4 was significantly greater in Group I than in Groups II and III (all P<0.01). PVST thickening at C2, C3, and C4 in Group I was 1.87 (14.12mm/7.54mm), 1.82 (12.90mm/7.07mm) and 1.71 (12.09mm/7.07mm) times of that in Group II, respectively. PVST thickening at C2, C3, and C4 in Group I was 2.66 (14.12mm/5.31mm), 1.50 (12.90mm/8.62mm) and 1.32 (12.09mm/9.18mm) times of that in Group III, respectively. The patients in Group I had significantly later postoperative extubation (Both P<0.01) than the patients in Groups II and III. None of the patients had postoperative re-intubation or dysphagia. We conclude that PVST swelling was greater in patients who underwent TARP internal fixation than in patients who underwent anterior C3/C4 or C5/C6 internal fixation. Hence, after TARP internal fixation, patients should be given proper respiratory tract management and monitoring.

Anterior reduction and C1-ring osteosynthesis with Jefferson-fracture reduction plate (JeRP) via transoral approach for unstable atlas fractures.

BACKGROUND: To introduce a novel transoral instrumentation in the treatment of unstable fractures of the atlas. METHODS: From January 2008 to May 2018, 22 patients with unstable C1 fractures who received Jefferson-fracture reduction plate (JeRP) via transoral approach were retrospectively analyzed. The case history and the radiographs before and after surgery were noted. The type of fracture, the reduction of the fracture, and position of the internal fixation were assessed through preoperative and postoperative CT scans. RESULTS: All 22 patients successfully underwent anterior C1-ring osteosynthesis using the JeRP system, with a follow-up of 26.84 ± 9.23 months. Among them, 9 patients had transverse atlantal ligament (TAL) injury, including 3 in Dickman type I and 6 in type II. The preoperative lateral mass displacement (LMD) decreased from 7.13 ± 1.46 mm to 1.02 ± 0.65 mm after the operation. Bone union was achieved in all patients without implant failure or loss of reduction. There were no surgery-related complications, such as wound infection, neurological deficit, or vertebral artery injury. However, atlantoaxial dislocation occurred in 3 patients with Dickman type I TAL injury 3 months postoperatively without any neurological symptoms or neck pain. CONCLUSIONS: Transoral C1-ring osteosynthesis with JeRP is an effective surgical strategy to treat unstable atlas fractures with a safe, direct, and satisfactory reduction. The primary indication for the JeRP system is an unstable fracture (Gehweiler type I/III) or/ and TAL injury (Dickman type II).

[An observation on risk of infection in treatment of craniovertebral junction disorders by transoral approach operation].

OBJECTIVE: To study the changes of bacterial flora after a series of preoperative oral disinfection and the postoperative recovery of patients with craniovertebral junction disorders who were treated with transoral approach operations. And to provide a theoretical basis for the prevention of postoperative complications such as infection. METHODS: The clinical data of 20 cases with craniovertebral junction disorders and treated with transoral approach operations between October 2009 and May 2010 were analyzed. There were 8 males and 12 females, aged 2-66 years (median, 34.5 years). According to the classification of American Spinal Injury Association (ASIA)，there were 4 cases of grade B, 8 of grade C, 6 of grade D, and 2 of grade E. The Japanese Orthopedic Association (JOA) score was 10.3±3.0. The mucosa samples of the posterior pharyngeal wall were sent for bacteria culture. These samples were collected by sterile cotton swabs at four crucial points including 3 days before operation/before gargling (T1), 3 days after continuous gargling by chlorhexidine acetate/after anesthesia intubation on the day of operation (T2), after intraoperative cleaning and washing of the mouth (T3), and after intraoperative iodophor immersion for 5-10 minutes (T4). The microflora was stained by means of smear and further counted after an investigation by microscope. The ASIA classification and the JOA scores were applied to evaluate the postoperative nerve function of the patients. A regular reexamination of cervical vertebra with X-ray film, CT, and MRI was conducted after operation to evaluate the reduction of atlantoaxial dislocation, internal fixation position, bone graft fusion, inflammatory lesion, and tumor resection in the craniovertebral junction. RESULTS: After a series of oral disinfection, the mucosa of the posterior pharyngeal wall of all the patients was in a sterile state, which was considered as type Ⅰ incision. All these 20 patients were treated with successful operations, without any intraoperative injury in vertebral artery and spinal cord, or any postoperative complications such as plate loosening, incision infection, or intracranial infection. All the patients were followed up 3-23 months, with an average of 5.15 months. The symptoms such as neck pain, limb numbness and weakness, neural symptoms, etc. were improved to different degrees after operation. The JOA score was improved to 13.4±1.9 at 3 months after operation, showing significant difference when compared with preoperative score ( t=8.677, P=0.000); and the atlantoaxial joints had been fused. At last follow-up, the ASIA grades were improved when compared with those before operation. CONCLUSION: It is safe and effective to cut the posterior pharyngeal muscle layer and implant internal fixation by means of transoral approach in the treatment of craniovertebral junction disorders.

Mild microwave ablation combined with HSP90 and TGF­ß1 inhibitors enhances the therapeutic effect on osteosarcoma.

Osteosarcoma is the most common malignant bone tumour and the second leading cause of cancer­related death in children and adolescents. Microwave ablation has an excellent therapeutic effect on bone tumours by instantaneously increasing the temperature in the tumour; however, there is a risk of damaging the surrounding healthy tissues by exposure to a high temperature when the treatment power is too large. In the present study, two anti­tumour reagents, a heat shock protein 90 (HSP90) inhibitor (PF­04929113) and a transforming growth factor­ß1 (TGF­ß1) inhibitor (SB­525334) were employed to enhance the therapeutic effect of mild­power microwave ablation. It was revealed that microwaving to 48˚C combined with HSP90 and TGF­ß1 inhibitors significantly increased the apoptotic rate of VX2 cells. The same results were observed during in vivo experiments using New Zealand rabbits to model osteosarcoma. In addition, the results indicated that the expression of cytochrome c, caspase­3 and caspase­9 were upregulated in response to the treatment, which indicated that the mitochondrial apoptotic signalling pathway had been activated. These findings may provide a novel strategy for the development of microwave ablation in osteosarcoma treatment, which could effectively kill tumour cells without damaging the surrounding normal tissues.

Formononetin inhibits osteosarcoma cell proliferation and promotes apoptosis by regulating the miR-214-3p/phosphatase and tensin homolog pathway.

BACKGROUND: Phytoestrogens have a similar molecular structure to estrogens which can produce either estrogenic or anti-estrogenic effects. It is generally believed that phytoestrogens combine with the estrogen receptor of osteosarcoma cells, affecting a variety of signal transduction pathways and cell metabolism, resulting in altered cell proliferation, differentiation, apoptosis, invasion and migration ability. Formononetin (FN) is the active ingredient of traditional Chinese medicine astragalus, angelica, and Pueraria lobate. Our study aims to detect the role of FN on MG-63 cell viability and apoptosis through regulating phosphatase and tensin homolog (PTEN) expression via MicroRNA-214-3p (miR-214-3p). METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Caspase 3 assay evaluated cell viability and apoptosis, respectively. Real-time quantitative polymerase chain reaction (qRT-PCR) and western blot evaluated the mRNA and protein expressions, respectively. The binding site of miR-214-3p/PTEN was detected via dual luciferase assay. RESULTS: FN suppressed cell viability and induced apoptosis, and decreased miR-214-3p level and promoted PTEN expression. PTEN was then regarded as a target of miR-214-3p, and FN improved PTEN level via inhibiting miR-214-3p. Further analysis showed that overexpressed miR-214-3p improved cell viability and suppressed apoptosis of MG-63 cells by inhibiting PTEN expression. CONCLUSIONS: Finally, our results revealed that FN inhibited cell viability and induced apoptosis by regulating miR-214-3p. FN acted as a new treatment for MG-63 cells via increasing PTEN level by inhibiting the miR-214-3p level.

Treatment of trauma-induced femoral head necrosis with biodegradable pure Mg screw-fixed pedicle iliac bone flap.

INTRODUCTION: The avascular necrosis of the femoral head represents the death of bone tissue due to the lack of blood supply. The disease has a progressive evolution; it leads to femoral head collapse and severe arthritis when left untreated. The application of a pedicled bone flap graft is an effective treatment for femoral head necrosis. A pure Mg screw is a kind of degradable screw that can fix the grafted bone flap and prevent long-term stress occlusion and secondary dissection. CASE PRESENTATION: The report shows the results of the treatment of traumatic femoral head necrosis with a pedicled bone flap with pure Mg screw. A patient had avascular necrosis of the femoral head after 2 years of internal fixation of the femoral neck fracture. We removed the patient's internal fixation hollow nail, cleaned the necrotic bone tissue and took part of the same ipsilateral pedicle iliac bone graft in the femoral head defect with biodegradable pure Mg screw fixation. Within 2 years after the surgery, the patients had no significant progressive necrosis of the femoral head. Postoperative Harris scores showed that the patient's left hip function was significantly improved compared with his preoperative state. The pure Mg screw in the body had gradually degraded. After 2 years, the screw's diameter had been significantly reduced compared with 3 days after the surgery. The postoperative Harris score showed that the patient's left hip function was significantly improved compared with the second preoperative examination. DISCUSSION: The discussion includes the reasons for the choices of surgical approaches, the mode of pure Mg screw degradation and the postoperative functional assessment of the patient's left hip. CONCLUSION: Pure Mg screw fixation pedicled bone flap transplantation is an effective surgical treatment for femoral head necrosis in young patients. Pure Mg screw is a biodegradable internal fixation device with good biocompatibility, which has a good clinical application prospects. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Degradable pure Mg screw has the potential to preserve hip joint therapy for the treatment of femoral head necrosis.

lncRNA-NEF is downregulated in osteosarcoma and inhibits cancer cell migration and invasion by downregulating miRNA-21.

Long non-coding RNA (lncRNA)-NEF inhibits cancer metastasis in hepatocellular carcinoma; however, its role in other malignancies is unknown. The present study revealed that plasma lncRNA-NEF was downregulated, while miRNA-21 was upregulated in patients with osteosarcoma compared with healthy controls. Plasma lncRNA-NEF and miRNA-21 were negatively correlated in patients with osteosarcoma and healthy controls. Downregulation of lncRNA-NEF and upregulation of miRNA-21 distinguished patients with osteosarcoma from healthy controls. lncRNA-NEF overexpression mediated the inhibition of miRNA-21 expression in osteosarcoma cell lines, while miRNA-21 overexpression did not significantly affect the expression of lncRNA-NEF. lncRNA-NEF overexpression inhibited, while miRNA-21 overexpression promoted, migration and invasion of osteosarcoma cell lines in vitro. miRNA-21 overexpression partially compensated the inhibitory effects of lncRNA-NEF overexpression on osteosarcoma cell migration and invasion. Therefore, lncRNA-NEF may inhibit cancer cell migration and invasion in osteosarcoma by downregulating miRNA-21.

miR-363 acts as a tumor suppressor in osteosarcoma cells by inhibiting PDZD2.

PDZ domain containing 2 (PDZD2) is a multi-PDZ domain protein that promotes the proliferation of insulinoma cells, and is upregulated during prostate tumorigenesis. However, the function of PDZD2 in other cancers, including osteosarcoma (OS), remains unclear. Dysregulation of microRNAs (miRNAs) contributes to tumor initiation, proliferation and metastasis, via the regulation of their target genes. The present study investigated the functions of miR-363 and PDZD2 in MG-63 OS cells. The results revealed that MG-63 cells contained low levels of miR-363, and that overexpression of miR-363 in MG-63 cells significantly inhibited the vitality, proliferation, and colony formation ability of the cells, but promoted their apoptosis and G1/S arrest by regulating proliferating cell nuclear antigen (PCNA) and caspase-3 expression. Additionally, miR-363 impaired the migration and invasion of MG-63 cells by regulating the epithelial-mesenchymal transition (EMT) phenotype. Notably, a bioinformatics analysis and luciferase reporter assay indicated that PDZD2 was a direct target of miR-363. miR-363 overexpression reduced PDZD2 protein levels and knockdown of PDZD2 suppressed the colony formation, migration and invasion of MG-63 cells, but promoted their apoptosis by regulating expression of PCNA, caspase-3, and the EMT phenotype. In vivo studies further confirmed that miR-363 functioned as tumor suppressor, by inhibiting tumor growth, promoting cell apoptosis, and reducing PDZD2 and PCNA levels and the prevalence of the EMT phenotype in tumor tissues. The present data demonstrated that downregulation of the tumor suppressor miR-363 may be involved in the development of osteosarcoma via regulation of PDZD2.

Exploration of TiO2 nanoparticle mediated microdynamic therapy on cancer treatment.

Radical therapy takes advantage of the reactive oxygen species produced in greater quantities within tumor cells than in normal cells. Here, for the first time, we explore a TiO2 nanoparticle mediated microwave induced radical therapy (termed as Microdynamic Therapy) as a new cancer treatment method. The experiments in vitro and in vivo demonstrate that colloidal TiO2 nanoparticles could significantly suppress the growth of osteosarcomas, even under low power (5 W) microwave (MW) irradiation for 5 min. The high photocatalytic activity of TiO2 nanoparticles efficiently utilizes the microwave-induced plasmonic effect for the formation of reactive oxygen species (ROS). Furthermore, TiO2 nanoparticles exhibit a higher cytotoxicity on cancer cells (osteosarcoma UMR-106 cells) than on normal cells (mouse fibroblast L929 cells). The effectiveness of TiO2 nanoparticles for microwave induced radical therapy demonstrates that this is a new landmark approach to treating cancers.

miRNA-21 inhibition inhibits osteosarcoma cell proliferation by targeting PTEN and regulating the TGF-ß1 signaling pathway.

The present study aimed to investigate the role of microRNA (miRNA)-21 in the growth of osteosarcoma. A total of 46 patients with osteosarcoma and 20 healthy controls were included in the study. The expression of miRNA-21 was detected by reverse transcription-quantitative polymerase chain reaction in tumor tissues and adjacent healthy tissues from patients with osteosarcoma, as well as the serum of patients with osteosarcoma and the healthy controls was. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic values of serum miRNA-21 for osteosarcoma at different T stages. Survival curves plotted using the Kaplan-Meier method were used to evaluate the prognostic value. miRNA-21 knockdown osteosarcoma cell lines were established and their effects on cell proliferation were explored using a Cell Counting Kit-8 assay. The effect of miRNA-21 knockdown on the protein expression of phosphatase and tensin homolog (PTEN) and transforming growth factor (TGF)-ß1 was detected by western blot analysis. The expression levels of miRNA-21 in tumor tissues were significantly higher compared with the adjacent healthy tissues in the majority of patients with osteosarcoma. The serum miRNA-21 increased as the T-stage of osteosarcoma increased. Serum miRNA-21 may be used to effectively diagnose osteosarcoma and predict the prognosis of the disease. miRNA-21 knockdown inhibited the proliferation of osteosarcoma and promoted the expression of PTEN and TGF-ß1 proteins in the osteosarcoma cells. However, TGF-ß1 inhibitor treatment reduced the inhibitory effects of miRNA-21 knockdown on osteosarcoma cell proliferation. In conclusion, miRNA-21 inhibition may inhibit osteosarcoma cell proliferation by targeting PTEN and regulating the TGF-ß1 signaling pathway.

Zero-Dimensional Carbon Dots Enhance Bone Regeneration, Osteosarcoma Ablation, and Clinical Bacterial Eradication.

Zero-dimensional carbon dots (CD) and their effects on osteogenesis have been rarely studied in bone repair scaffolds. Here, we fabricate a novel CD doped chitosan/nanohydroxyapatite (CS/nHA/CD) scaffold with full potential to promote bone regeneration by a facile freeze-drying method. The CS/nHA/CD scaffolds enhanced cell adhesion and osteoinductivity in rat bone mesenchymal stem cells by up-regulating genes involved in focal adhesion and osteogenesis in vitro, which significantly improved the formation of vascularized new bone tissue at 4 weeks compared to pure CS/nHA scaffolds in vivo. Inspired by the excellent photothermal effect of CD, the scaffolds were applied in tumor photothermal therapy (PTT) under near-infrared (NIR) irradiation (808 nm, 1 W/cm2). The scaffolds significantly inhibited osteosarcoma cell proliferation in vitro and effectively suppressed tumor growth in vivo. Moreover, the CS/nHA/CD scaffolds possessed distinct antibacterial properties toward clinically collected S. aureus and E. coli, and their antibacterial activity was further enhanced under NIR irradiation. This work demonstrates that zero-dimensional CD can enhance the osteogenesis-inducing property of bone repair scaffolds and that CD doped scaffolds have potential for use in PTT for tumors and infections.

A New Treatment Modality for Rheumatoid Arthritis: Combined Photothermal and Photodynamic Therapy Using Cu7.2 S4 Nanoparticles.

Rheumatoid arthritis (RA) is a worldwide inflammatory disease that seriously threatens human health and needs more effective treatment approaches. Near infrared (NIR) light can efficiently penetrate inflamed joints affected by RA, so phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), may provide new opportunities. In this work, the unique Cu7.2 S4 nanoparticles (NPs) are prepared for RA treatment enlightened by the fact that copper (Cu)-based nanomaterials can simultaneously serve as PTT agents and photosensitizers (for PDT). Meanwhile, Cu can promote ostogenesis and chondrogenesis. The Cu7.2 S4 NPs combined with NIR (808 nm, 1 W cm-2 ) irradiation not only achieve better bone preservation, including higher bone mineral density (BMD) and bone volume/total volume, but also inhibit inflamed synovial invasion, cartilage erosion, and expression of proinflammatory cytokines in vivo. Moreover, the Cu7.2 S4 NPs can effectively kill clinical pathogenic Staphylococcus aureus and Escherichia coli to prevent bacterial infection during intra-articular injection. Therefore, the combined PTT and PDT using the multifunctional Cu7.2 S4 NPs could be a novel RA treatment modality with full potential.

Atlantoaxial Joint Distraction for the Treatment of Basilar Invagination: Clinical Outcomes and Radiographic Evaluation.

OBJECTIVE: To investigate the causes of partial remission in patients with basilar invagination (BI) and irreducible atlantoaxial dislocation (IAAD) treated with transoral atlantoaxial reduction plate (TARP) without odontoidectomy and quantify the distance of odontoid descent. METHODS: Between August 2010 and July 2012, 22 consecutive patients with BI with IAAD who underwent TARP surgery were reviewed. The preoperative and postoperative radiographic parameters were evaluated. Follow-up data and the symptom treatment interval (STI), defined as the interval between the onset of symptoms and surgical treatment, were assessed. Neurological function was evaluated as neurologic improvement, defined as ([Postoperative Japanese Orthopedic Association (JOA) score] - [Preoperative JOA score])/(17 - [Preoperative JOA score]). The patients were assigned to group A (<50%) or group B (≥50%) based on their level of neurologic improvement. RESULTS: All 22 patients improved clinically to varying degrees. The mean preoperative STI was 105.6 ± 67.6 months for group A and 45.3 ± 46.7 months for group B (P < 0.05). There were no significant between-group differences in follow-up (P > 0.05) or with respect to radiographic parameters (P > 0.05). Persistent brainstem compression was observed in 1 patient, whose symptoms were not adequately relieved after revision surgery (transoral odontoidectomy and posterior decompression and fusion). No fixation failure was observed. CONCLUSIONS: Descent of the odontoid process is useful for treating basilar invagination. TARP surgery without odontoidectomy may pull the dens caudally and ventrally to achieve sufficient decompression of the spinal cord. Neurologic improvement may be associated with STI.

Multifunctional Copper-Containing Carboxymethyl Chitosan/Alginate Scaffolds for Eradicating Clinical Bacterial Infection and Promoting Bone Formation.

Repairing infected bone defects relies on a scaffold that can not only fill the defects to promote bone formation but also kill clinically present bacterial pathogens such as Staphylococcus aureus (S. aureus). To meet this demand, here, we develop a new copper (Cu) containing natural polymeric scaffold with a full potential for repairing infected bone defects. Instead of directly adding antibacterial Cu2+ ions to the polymer mixtures, which caused uncontrolled polymer cross-linking, we added Cu nanoparticles to the mixture of anionic carboxymethyl chitosan (CMC) and alginate (Alg). Then, the Cu2+ ions released from the Cu nanoparticles gradually cross-linked the polymer mixtures, which was further turned into a scaffold (CMC/Alg/Cu) with an interconnected porous structure by freeze-drying. We found that the CMC/Alg/Cu scaffolds showed significantly improved capabilities of osteogenesis and killing clinical bacteria compared to CMC/Alg scaffolds fabricated by the same procedure but without adding Cu nanoparticles. Specifically, in vitro studies showed that the CMC/Alg/Cu scaffolds with excellent biocompatibility could enhance preosteoblastic cell adhesion by upregulating the expression level of adhesion-related genes (focal adhesion kinase (FAK), paxillin (PXN), and vinculin (VCL)), promoting osteogenic differentiation and mineralization by upregulating the osteogenesis-related gene expression and extracellular calcium deposition. In vivo studies further demonstrated that CMC/Alg/Cu scaffolds could induce the formation of vascularized new bone tissue in 4 weeks while avoiding clinical bacterial infection even when the implantation sites were challenged with the clinically collected S. aureus bacteria. This work represents a facile and innovative approach to the fabrication of Cu containing polymer scaffolds that can potentially be used to repair infected bone defects.

High-activity chitosan/nano hydroxyapatite/zoledronic acid scaffolds for simultaneous tumor inhibition, bone repair and infection eradication.

Implanted biomaterials combined tumor inhibition and bone repair property are urgently needed to address the huge bone destruction and the high local recurrence following primary surgery in bone tumor therapy. In this work, a high-activity chitosan/nano hydroxyapatite (CS/nHA) scaffold containing zoledronic acid (CS/nHA/Zol) was prepared with a facile method. The prepared CS/nHA/Zol scaffolds exhibited excellent tumor inhibition property towards giant cell tumor of bone (GCT) in vitro through inducing cells apoptosis by up-regulating pro-apoptosis genes expression and reducing the osteoclastic activity of tumor cells by down-regulating osteoclastic genes. Meanwhile, the prepared scaffolds possessed well biocompatibility and osteoinductivity as compared to pure CS/nHA scaffolds. Furthermore, the prepared scaffolds also presented outstanding antibacterial activity against clinical pathogenic S. aureus and E. coli. These overall findings successfully demonstrated the prepared CS/nHA/Zol scaffolds had a multifunction of tumor therapy, bone repair, and antibacterium, which provides a new approach possessed promising advantages in bone tumor therapy.

Multifunctional Cu39S28 Hollow Nanopeanuts for In Vivo Targeted Photothermal Chemotherapy.

Actively targeted hollow nanoparticles may play key roles in precise anti-cancer therapy. Here, unique Cu39S28 hollow nanopeanuts (HNPs) were synthesized via a facile one-step method and the formation mechanism was illustrated. The as-synthesized Cu39S28 HNPs exhibit outstanding photothermal conversion efficiency (41.1%) and drug storage capacity (DOX, 99.5 %). At the same time, the DOX drug loading nanocomposites have shown great sensitive response of release to either pH value or near infrared ray (NIR). In particular, the folic acid (FA) can easily conjugate with the synthesized Cu39S28 HNPs without further modification to get a targeted effect. The FA modified Cu39S28 HNPs showed an efficiently targeting effect in vitro and could considerably enhance the tumor-targeting effect more than 10 times in vivo. Moreover, the synthetical hyperthermia and drug release from Cu39S28 HNPs when under 808 nm laser could significantly improve the therapeutic efficacy compared with photothermal or chemotherapy alone both in vitro and in vivo. The histological studies in main organs also proved the well biocompatibility, while the tumor sites were in seriously destruction due to the accumulation of the nanocomposites and the combined photothermal chemo therapy effect. Therefore, the multi-functional nanocomposites is excellent antitumor agents due to their superb therapy effect in breast cancer.

Implantation of the anterior atlantoaxial lateral mass intervertebral cage using the transoral approach.

BACKGROUND: The purpose of this study was to evaluate the possibility of implanting the anterior atlantoaxial lateral mass intervertebral cage, a new type of fixation, by the transoral approach. METHOD: This study examined the possibility of implantation in vivo by the quantitative measurement on the dry atlantoaxial bone and implantation of the anterior atlantoaxial lateral mass intervertebral cage in specimens. Anterior atlantoaxial lateral mass intervertebral cages were implanted in 10 atlantoaxial joint specimens using the transoral approach. Eight anatomical parameters (width, the thickness, ordinates, abscissas, and declination angles of the mass) from each of the 30 dry atlas and axis bone specimens were measured. These parameters determined the size and the design of the cage and the way of implantation. RESULTS: The course of the vertebral artery forms the safe boundary for transoral surgery. The shape of the area of work exposure was an inverted trapezoid. In specimens, the anterior atlantoaxial lateral mass intervertebral cages could be successfully implanted using the transoral approach. The parameters of the human atlantoaxial lateral masses exposed anteriorly showed that there was enough space, for the safe anterior implantation of the cage. The surgery using the transoral atlantoaxial reduction and plate makes possible the implantation of the anterior cage. CONCLUSION: The implantation of anterior atlantoaxial lateral mass intervertebral cage through transoral approach is possible.

Cuff-leak test combined with interventional bronchoscopy benefits early extubation for patients who received tarp surgery.

PURPOSE: This study explored the performance characteristics of a cuff-leak test (CLT) combined with interventional fiberoptic bronchoscopy (FBS) for evaluating whether early nasoendotracheal extubation was possible for patients who had received transoral atlantoaxial reduction plate (TARP) internal fixation surgery. METHODS: 318 patients who underwent surgery were retrospectively analyzed (between January 2006 and December 2012). Extubation was performed by conventional approach (CA group, until December 2008) and improved approach (IA group, from January 2009) including CLT and an interventional FBS procedure. The extubation success within 1-3 days after surgery, incidence of postextubation stridor and tracheal reintubation were examined. RESULTS: More IA-treated patients experienced extubation during the first 2 days than those CA-treated, median extubation time was 3 (2, 3) days in the CA group and 2 (1, 2) days in the IA group (all P < 0.01). The incidence of stridor and reintubation was 5.69 and 0.57 % in IA and 11.98 and 4.93 % in CA, respectively (both P < 0.05). For the CLT-positive patients in the IA group that remained intubated until day 3-4, interventional FBS was applied for safe extubation and achieved 100 % success. CONCLUSION: Early extubation through IA is safe and interventional FBS assists successful extubation for CLT-positive patients who underwent TARP surgery.