Effect of ticagrelor and clopidogrel dual antiplatelet therapy on MPVLR, MAADP, and AA inhibition rate in acute coronary syndrome patients after percutaneous coronary intervention.

OBJECTIVE: To explore the effects of ticagrelor and clopidogrel dual antiplatelet therapy on the mean platelet volume-to-lymphocyte ratio (MPVLR), maximum amplitude of adenosine diphosphate-induced platelet-fibrin clots (MAADP), and arachidonic acid (AA) inhibition rates in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). METHODS: A total of 120 patients with ACS undergoing elective PCI in our hospital between March 2020 and November 2021 were recruited. Patients were divided into 2 groups using the random number table method, with 60 patients in each group. The control group received clopidogrel + aspirin dual antiplatelet therapy, while the study group received ticagrelor + aspirin dual antiplatelet therapy. MPVLR, MAADP, and AA inhibition rates were compared between the 2 groups. Platelet activation indices, platelet micro PNA-223, and platelet gelsolin levels were measured before and 4 weeks after PCI. Changes in cardiac function indices, bleeding rates, and major adverse cardiovascular events (MACE) were compared between groups. RESULTS: The MAADP score of the study group was lower than that of the control group 3 days after surgery (P < .05). Compared with before surgery, CD62p, CD63, miR-223, PAC-1, platelet membrane glycoprotein IIb/IIIa complex, and gelsolin levels markedly decreased in both groups 4 weeks after surgery (P < .05). The platelet activation index and platelet miR-223 and gelsolin levels were significantly lower in the study group than in the control group 4 weeks after surgery (P < .05). The overall platelet inhibition effect was significantly better in the study group than in the control group (P < .05). Compared with before surgery, the left ventricular ejection fraction and stroke volume were significantly increased, and the left ventricular end-diastolic volume and left ventricular end-diastolic diameter significantly decreased in both groups 4 weeks after surgery (P < .05). No significant differences were found between the 2 groups in terms of the incidence of bleeding events or MACE (P > .05). CONCLUSION: Ticagrelor is more effective than clopidogrel for platelet inhibition after PCI in patients with ACS and is worthy of clinical recommendation.

The efficacies and biomarker investigations of antiangiogenic agents and PD-1 inhibitors for metastatic soft tissue sarcoma: A multicenter retrospective study.

Objective: To investigate the efficacy and safety of antiangiogenesis-immunotherapy in patients with advanced STS in China, and to explore the potential factors of prognosis. Patients and Methods: This retrospective study was conducted at three hospitals in China, and the patients with metastatic STS who were ineligible for or declined anthracycline-based chemotherapy received antiangiogenic agents (anlotinib or apatinib) plus programmed death-1 (PD-1) inhibitors (camrelizumab or sintilimab) between June 2019 and May 2022. The primary endpoint was progression-free survival rate at 6 months (6-month PFSR), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) and toxicity. Biomarkers that might affect the prognosis were explored. Results: Thirty-nine patients were included: five patients with alveolar soft tissue sarcoma (ASPS) and 34 with non-ASPS. With a median follow-up of 18.2 months, the 6-month PFSR was 51.3%, with the ORR of 20.5% and DCR of 76.9%. The median PFS and OS were 7.0 months and 17.2 months. The 6-month PFSR for patients with ASPS and non-ASPS was 80.0% and 47.1%, respectively. The most common adverse events were hypothyroidism (56.4%), followed by fatigue (46.2%), and hypertriglyceridemia (43.6%). No treatment-related deaths were observed. Patients with low baseline NLR (NLR < 4) had better 6-month PFSR than those with high NLR (NLR ≥ 4) (82.4% vs. 31.6%). Conclusion: Antiangiogenic agents plus PD-1 inhibitors showed acceptable toxicity and promising efficacy in patients with advanced STS, especially patients with ASPS, and a low NLR might serve as a reliable biomarker for 6-month PFSR, PFS, and OS. It provides a reference for randomized controlled trials.

Long-term survival of hybrid total hip replacement for prior failed proximal femoral nail antirotation: a retrospective study with a median 10-year follow-up.

BACKGROUND: Hybrid total hip replacement (THR) is commonly used in the management of proximal femur fractures in elderly individuals. However, in the context of the revision, the literature on hybrid THR is limited, and differences in the long-term survival outcomes reported in the literature are obvious. This retrospective study aimed to evaluate the long-term survival of hybrid THR for failed proximal femoral nail antirotation (PFNA) in elderly individuals aged ≥ 75 years. METHODS: An observational cohort of 227 consecutive individuals aged ≥ 75 years who experienced hybrid THRs following prior primary PFNAs was retrospectively identified from the Joint Surgery Centre, the First Affiliated Hospital, Sun Yat-sen University. Implant survival was estimated using the Kaplan-Meier method. The primary end point was the implant survivorship calculated using the Kaplan-Meier method with revision for any reason as the end point; secondary end points were the function score measured using the modified Harris Hip Score (mHHS) and the incidence of main orthopaedic complications. RESULTS: In total, 118 individuals (118 THRs) were assessed as available. The median follow-up was 10 (3-11) years. The 10-year survivorship with revision for any reason as the endpoint was 0.914 (95% confidence interval [CI], 0.843-0.960). The most common indication for revision was aseptic loosening (70.0%), followed by periprosthetic fracture (30.0%). At the final follow-up, the median functional score was 83.6 (79.0-94.0). Among the 118 patients included in this study, 16 experienced 26 implant-related complications. The overall incidence of key orthopaedic complications was 13.5% (16/118). CONCLUSION: For patients aged ≥ 75 years old with prior failed PFNAs, hybrid THR may yield satisfactory long-term survival, with good functional outcomes and a low rate of key orthopaedic complications.

Efficacy and safety of anlotinib in patients with unresectable or metastatic bone sarcoma: A retrospective multiple institution study.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) such as cabozantinib, regorafenib have demonstrated encouraging activity in prolonging progression-free survival (PFS) in several bone sarcoma entities in prospective clinical trials. This retrospective study aims to analyze the safety and efficacy of anlotinib, a novel multi-target TKI, in patients with locally unresectable or metastatic bone sarcoma at three institutions. METHODS: Patients with advanced bone sarcoma administered anlotinib 12 mg once daily, 2 weeks on/1 week off, from June 2018 to June 2020, until disease progression or intolerance of treatment. The primary endpoints were objective response rate (ORR) and PFS. RESULTS: Forty-eight patients were analyzed: 27 have osteosarcoma, 9 have chondrosarcoma, 8 have Ewing's sarcoma, and 3 have chordoma. The median age was 24 years (range, 16-68 years), and the median number of prior regimens was 1 (range, 0-4). Until the final follow-up, five patients obtained a partial response and while 24 achieved stable disease. The ORR in all patients was 10.4%, and the median PFS was 4.6 months, with a progression-free rate (PFR) at 3 months and 6 months of 72.9% and 35.4%, respectively. The ORR and median PFS varied much among tumor subtypes. The most frequent grade 3-4 adverse events (AEs) were pneumothorax, hand-foot syndrome, cholesterol elevation, hypertriglyceridemia, and fatigue. No patients died from anlotinib-related AEs during the study period. CONCLUSIONS: Anlotinib may show promising antitumor activity in unresectable or metastatic bone sarcoma. The ORR and median PFS of anlotnib are similar to those of other targeted drugs in different subtypes of sarcomas. The AEs were generally mild and tolerated well. Further studies of anlotinib in selected subtypes of bone sarcoma are needed.

Efficacy and safety of toripalimab combined with doxorubicin as first-line treatment for metastatic soft tissue sarcomas: an observational study.

Programmed cell death protein 1 (PD-1) inhibitors have demonstrated promising activity among patients with advanced soft tissue sarcomas (STS) in phase II trials. The purpose of this study was to assess the efficacy and safety of toripalimab (a novel PD-1 inhibitor) combined with doxorubicin as first-line treatment in patients with metastatic STS between December 2018 and September 2019. A total of 30 patients with metastatic STS were included and followed up retrospectively. One patient had complete response (CR), 10 patients obtained partial response, and 13 patients achieved stable disease. The objective response rate was 36.7% and the disease control rate was 80%. The median progression-free survival (PFS) was 8 months (95% CI: 6.30-10.64). The most frequent any grade adverse events were nausea (66.7%), fatigue (60%), and vomiting (40%). Neutropenia (20%) was the most common grade 3/4 adverse events, followed by leucopenia (13.3%) and febrile neutropenia (6.7%). No death related to treatment was observed during the drugs administration. Toripalimab combined with doxorubicin is effective in patients with metastatic STS as first-line treatment with manageable adverse events.

Efficacy and safety of Shexiang Baoxin Pill combined with Western medicine in the treatment of acute myocardial infarction: A single-center, double-blind, randomized controlled trial.

BACKGROUND: The morbidity and mortality of acute myocardial infarction are on the rise, and the efficacy of conventional treatment is limited. Shexiang Baoxin Pill is a kind of proprietary Chinese medicine, which has been widely used in the treatment of acute myocardial infarction in China, and has certain advantages. At present, there is a lack of strict randomized controlled trials to verify the efficacy and safety of Shexiang Baoxin Pill combined with Western medicine in the treatment of acute myocardial infarction. Therefore, the purpose of this randomized controlled trial is to evaluate the clinical efficacy of Shexiang Baoxin Pill combined with Western medicine in the treatment of acute myocardial infarction. METHODS: This is a prospective randomized controlled trial to study the efficacy and safety of Shexiang Baoxin Pill combined with Western medicine in the treatment of acute myocardial infarction. It is approved by the Clinical Research Society of our hospital. According to 1:1, the patients will be randomly divided into observation group (Shexiang Baoxin Pill combined with Western medicine group) and control group (routine Western medicine group). The patients in the 2 groups will be treated continuously for 4 weeks and followed up for 3 months. Pay attention to its curative effect index and safety index. The observation indexes included total effective rate of improvement of cardiac function, left ventricular ejection fraction (LVEF), endothelin (ET), nitric oxide (NO) level, interleukin-6 (IL--6), adverse reactions, and so on. We will analyze the structure by SPSS version 19.0. DISCUSSION: This study will evaluate the efficacy and safety of Shexiang Baoxin Pill combined with Western medicine in the treatment of acute myocardial infarction. The results of this experiment will provide clinical basis for Shexiang Baoxin Pill combined with Western medicine in the treatment of acute myocardial infarction. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/PYJTK.

Diagnostic value of copeptin combined with hypersensitive cardiac troponin T detection in early acute myocardial infarction: A protocol of randomized double-blind diagnostic trial.

BACKGROUND: The sensitivity and specificity of the routine detection of acute myocardial infarction (AMI) in early diagnosis are not high, which can not meet the clinical needs. Copeptin combined with hypersensitive cardiac troponin T (hs-cTnT) is a new detection scheme, and its value in the early diagnosis of acute myocardial infarction is still unclear. Accordingly, the aim of this study is to evaluate the diagnostic value of copeptin combined with hypersensitive troponin T detection in early acute myocardial infarction. METHODS: This is a prospective, randomized; double-blind diagnostic trial to investigate the diagnostic value of copeptin combined with hypersensitive troponin T detection in early acute myocardial infarction. Approved by the clinical research ethics of our hospital. Patients were randomly divided into one of 2 test protocols: (A) copeptin combined with hs-cTnT group and (B) cardiac troponin I (cTnI) group. Patients, doctors, nurses, inspectors, and data-gathering assistants were blinded to group allocation. We will focus on the sensitivity comparison of the 2 detection methods at different time periods and the sensitivity and specificity comparison of the two detection methods. Data were analyzed using the statistical software package SPSS version 25.0 (Chicago, IL). DISCUSSION: The purpose of this study is to evaluate the diagnostic value of copeptin combined with hypersensitive cardiac troponin T detection in early acute myocardial infarction. The results of this study will establish clinical evidence for the detection of high sensitivity cardiac troponin T in the early diagnosis of acute myocardial infarction. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval was not required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/6TE5Z.

Safety and efficacy of combination therapy with apatinib and doxorubicin in metastatic soft tissue sarcomas: an observational study from multiple institutions.

Purpose: Apatinib has shown effectiveness in treating sarcoma. This study aimed to assess the safety and efficacy of apatinib and doxorubicin combination therapy in metastatic soft tissue sarcomas (STS) and to compare the therapeutic effects of two treatments (apatinib after doxorubicin vs apatinib plus doxorubicin) on STS. Patients and methods: A total of 76 patients with metastatic STS who received apatinib and doxorubicin between May 2016 and June 2017 were retrospectively reviewed. Patients were divided into either the apatinib after doxorubicin group (in which apatinib was used after six cycles of doxorubicin chemotherapy) or the apatinib plus doxorubicin group (in which apatinib was used in combination with doxorubicin chemotherapy). Results: There were 55 patients in the apatinib after doxorubicin group and 21 patients in the apatinib plus doxorubicin group. There were significant differences between the apatinib plus doxorubicin group and the apatinib after doxorubicin group in the objective response rate (57.14% vs 25.45%, respectively, p=0.016) and average change from baseline in the target lesion size (-41.71±43.75% vs -1.89±51.61%, respectively, p=0.03). There were no significant differences in disease control rate (85.71% vs 63.64%, p=0.093) and median progression-free survival (8.8 months vs 10.3 months, p=1). Grade 3-4 adverse events were more common with apatinib plus doxorubicin than with apatinib after doxorubicin, and these included leukopenia (5.45% vs 38.1%, respectively, p=0.001), anemia (7.27% vs 28.57%, respectively, p=0.023), oral mucositis (3.64% vs 19.05%, respectively, p=0.046), transaminase increases (0% vs 14.29%, respectively, p=0.011). Conclusion: Our results do not support the use of apatinib plus doxorubicin for metastatic STS unless the specific objective is tumor shrinkage.

Upregulation of ALDH1B1 promotes tumor progression in osteosarcoma.

Osteosarcoma (OS) is the most common primary malignant bone tumor in childhood and adolescence with poor prognosis. The mechanism underlying tumorigenesis and development of OS is largely unknown. ALDH1B1 has been reported to involve in many kinds of human cancers and functions as an oncogene, but the role of ALDH1B1 in OS has not been investigated comprehensively. In the present study, we aimed to examine clinical value and biological function of ALDH1B1 in OS. Firstly, we investigated the roles of ALDH1B1 on an OS tissue microarray (TMA) as well as two OS cohorts from GEO database. We found that ALDH1B1 was significantly up-regulated in OS tissues and was independently associated with poor prognosis. Moreover, ALDH1B1 silencing could suppress the proliferation, migration, invasion in vitro and inhibit the growth of xenograft tumor and of OS cells in vivo. Additional, ALDH1B1 knockdown increased the apoptosis rate and lead to cell cycle arrest in G1 stage of OS cell in vitro. More importantly, the inhibition of ALDH1B1 expression could increase the sensitivity of OS cells to chemotherapy, which suggested that ALDH1B1 might be served as a therapeutic target to reverse drug resistance in chemotherapy in OS patients. Taken together, our founding suggested that ALDH1B1 contributes to OS tumor progression and drug resistance, which may represent a novel prognostic marker and potential therapeutic target for OS patients.

Treatment of osteosarcoma around the knee in skeletally immature patients.

Limb sparing surgery in growing young patients with malignant tumors is difficult as invasion of the physis by the tumor or surgical resection through the metaphysis may cause significant limb discrepancy following surgery. At present, hinged tumor prosthesis or biological reconstructions are the main methods following tumor resection in these patients. The aim of the present study was to assess different procedures for the treatment of osteosarcoma around knee joints in immature patients. A retrospective study of 56 patients (<15 years old, open physis) who had been treated for osteosarcoma around the knee joint between January 2007 and December 2015 was performed. Clinical data collected included patient demographics (age at diagnosis, sex and date of diagnosis), tumor characteristics [location, Enneking stage and subtype on magnetic resonance imaging (MRI)], treatment (response to neoadjuvant chemotherapy and type of primary surgery) and clinical outcomes (limb function, discrepancy and overall survival). The median age at the time of diagnosis was 12.14 years (range, 3-15 years). There were 32 male patients (57.1%). A total of 41 (82%) tumors were located at the distal femur, and 15 (18%) at the proximal tibia. A total of 49 (87.5%) patients were diagnosed with stage IIB tumors, and 7 (12.5%) had stage III, according to the Enneking stage classification. Different surgical methods, including amputation, rotation-plasty, endoprosthesis and biological instructions (e.g., allograft) were performed according to MRI type classification. During follow-up, 21 patients (37.5%) succumbed to disease. The Musculoskeletal Tumor Society score ranged from excellent to fair functional result. Recurrence (2 cases, 16.67%) and infection (2, cases, 16.67%) were the main complications following endoprosthesis replacement, while delayed union (12 cases, 57.14%) and fracture (3 cases, 14.29%) were the main causes for biological reconstructions. Limb-length discrepancy ranged from 0-10 cm in limb-saving surgery. The overall survival rate was 57.66% with different cohorts in Enneking stages IIB and III, with or without involvement of the physis and different cycles of chemotherapy. Results of the present study indicated that different limb saving surgeries, including epiphysis/physis preservation with biological construction in patients with MRI types I to III and endoprosthetic/osteoarticular reconstruction in patients with MRI types IV and V, are useful in the management of osteosarcoma in growing young patients with proper surgery indications, and knee joint function was maintained with acceptable complications including limb discrepancy, delayed union, infection, recurrence and fracture.

Three-dimensional (3D) culture in sarcoma research and the clinical significance.

Sarcomas are rare malignant tumors that arise from transformed cells of mesenchymal origin. Despite the progress in diagnosis and treatment, sarcomas have a high mortality rate due to local recurrence, metastasis, and the development of drug resistance to chemotherapy. New models for sarcoma research are required to further understand the disease and to develop new therapies. In vitro sarcoma modeling is challenging because of significant genetic heterogeneities, diverse pathological, and overlapping clinical characteristics. Studies on the mechanisms of recurrence, metastasis, and drug resistance in sarcoma have resulted in the generation of novel three-dimensional (3D) culture models for sarcoma research. 3D culture models aim to recapitulate the tumor microenvironment that plays a critical role in the pathogenesis of sarcoma using biomaterial scaffolds of natural biological materials and artificial polymers. An ideal 3D culture model can properly mimic not only the microenvironment, oncogenesis, and maintenance of sarcoma cell growth, but also imitate the interactions between cells and to the extracellular matrix. More recently, 3D cell culture has been used to research the biological behavior and mechanism of chemotherapy and radiotherapy resistance in different sarcoma models. Ultimately, findings using 3D models that more accurately reflect human sarcoma biology are likely to translate into improved clinical outcomes. In this review, we discuss the most recent advances of 3D culture technologies in sarcoma research and emerging clinical applications.

Correlations Between Hector Battifora Mesothelial-1 (HBME-1) Expression and Clinical Pathological Characteristics and Prognosis of Osteosarcoma Patients.

BACKGROUND The aim of this study was to investigate the correlation between Hector Battifora mesothelial-1 (HBME-1) expression and the clinical pathological characteristics and prognosis of osteosarcoma (OS). MATERIAL AND METHODS HBME-1 expression was assessed using immunohistochemistry in OS tissues (n=152), osteochondroma tissues (n=91), and normal bone tissues (n=74). We carried out a follow-up lasting 8-60 months to investigate HBME-1 expression and its correlations with the clinical pathological characteristics and prognosis of OS. RESULTS HBME-1 was highly expressed in OS tissues compared with osteochondroma tissues and normal bone tissues, and was highly expressed in osteochondroma tissues compared with normal bone tissues (all P<0.05). HBME-1 expression was correlated with clinical stages, postoperative recurrence, metastasis, and 5-year survival (all P<0.05). The area under the receiver operating characteristics curve of HBME-1 expression was 0.864, with sensitivity of 80.92%, specificity of 91.89%, and accuracy of 84.51%. The survival rate was lower in the HBME-1 positive expression group than the HBME-1 negative expression group (P<0.05). Clinical stages, metastasis, and HBME-1 expression were independent risk factors for the survival of patients with OS (all P<0.05). CONCLUSIONS HBME-1 expression was correlated with the occurrence and development of OS. HBME-1 positive expression was a risk factor for the prognosis of OS.

Effect of stromal cell-derived factor-1 on myocardial apoptosis and cardiac function recovery in rats with acute myocardial infarction.

The aim of the study was to investigate the effect of stromal cell-derived factor-1 (SDF-1) on myocardial apoptosis and cardiac function recovery in rats with acute myocardial infarction (AMI) and the mechanism of the Toll-like receptor (TLR)-4/nuclear factor-κB (NF-κB) signaling pathway. A total of 64 healthy male F344 rats were randomly divided into the sham operation, model, SDF-1 intervention and SDF-1 antibody groups, with 16 rats in each group. The method of Olivette was used to establish the AMI model by ligation of the left anterior descending artery. Day 1 after establishing the animal model, the rats in the SDF-1 intervention group were injected with 10 µl recombinant SDF-1 (400 ng/ml) in five regions including the myocardial infarction area and the four surrounding areas. The rats in the model group were injected with 10 µl normal saline including the myocardial infarction area and the four surrounding areas, and those in the SDF-1 antibody group were injected with 1 ml SDF-1 antibody (2 µg/ml). Four rats were sacrificed after 1, 3, 7 and 14 days after the intervention, and the analysis was carried out. TUNEL in situ labeled apoptotic cells were used for cell counting, and immunohistochemical staining was performed to measure vascular density. The animal echocardiographic measurement was for the left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVESd), left ventricular fractional shortening (FS) and ejection fraction (EF) values. The results showed that the number of apoptotic cells in the SDF-1 treatment group was significantly lower than those in the other groups at each time-point. The vessel densities in the 3-14 days were significantly greater than those in other groups. At each time-point, the LVEDd and LVESd values were smaller compared with the model group, but greater than the sham operation group and decreased over time. FS and EF values were higher than those in the model group at each time-point, but less than those of the sham operation group and increased over time. The expression levels of TLR-4 and NF-κB at each time-point were significantly higher than those of the remaining groups (p<0.05). In conclusion, SDF-1 is capable of decreasing the apoptosis of cardiac muscle cells in AMI, promoting angiogenesis and improving cardiac function, which may be associated with the activation of the TLR-4/NF-κB signaling pathway.

Different methods for inducing adipose-derived stem cells to differentiate into Schwann-like cells.

INTRODUCTION: The aim of the study was to explore an effective method to induce adipose-derived stem cells (ADSCs) to differentiate into Schwann-like cells in vitro. MATERIAL AND METHODS: Reagents were applied in two different ways (Dezawa inducing method and modified inducing method) in which inducers including ß-mercaptoethanol (ß-ME), all-trans-retinoic acid (ATRA), type I collagenase, forskolin, heregulin, basic fibroblast growth factor (BFGF) and brain-derived neurotrophic factor (BDNF) were used in different ways to induce ADSCs of rats to differentiate into Schwann-like cells. After induction, the cell morphologic characteristics and the cellular immunohistochemical staining positive rate of anti-S100 and anti-GFAP (glial fibrillary acidic protein) antibodies and the gray value of immunocytochemical dye with anti-S100 and anti-GFAP antibodies and cell activity measured by the MTT method were compared with each other to evaluate the induction effects. RESULTS: Both methods can induce differentiation of ADSCs of rats into Schwann-like cells, but the cellular morphology of the modified method was more similar to Schwann cells than that of the Dezawa inducing method, there was a higher cellular immunohistochemical staining positive rate and staining grey value in immunocytochemical dye with anti-S100 and anti-GFAP antibodies, and less damage in the cell activity of the modified inducing method than that of the Dezawa inducing method. CONCLUSIONS: The effect of the modified method to induce ADSCs to differentiate into Schwann-like cells in vitro is superior to that of the Dezawa inducing method.

Knockdown of TRAF4 expression suppresses osteosarcoma cell growth in vitro and in vivo.

Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) is an adapter molecule that is overexpressed in certain cancers. TRAF4 is overexpressed in osteosarcoma tissues and osteosarcoma cells. Using the technique of RNA interference, the expression of TRAF4 in the human osteosarcoma Saos-2 cell line was shown to be downregulated. The proliferation, cell cycle arrest and apoptosis ability of Saos­2 cells were examined, as was tumor development in a xenograft mouse model. The results showed that the TRAF4 knockdown exerts inhibitory effects on the proliferation ability of Saos-2 cells and tumor development in a xenograft mouse model. Simultaneously, it was found that TRAF4 knockdown led to cell cycle arrest in the G1 phase and promoted Saos-2 cell apoptosis. Following TNF-α treatment, the expression of nuclear factor κB was significantly reduced in the TRAF4­small interfering RNA group. These results indicate that TRAF4 regulated osteosarcoma cell growth in vitro and in vivo, and offers a candidate molecular target for osteosarcoma prevention and therapy.

Preliminary clinical research on epiphyseal distraction in osteosarcoma in children.

BACKGROUND: The feasibility of distal femur epiphysis preservation through epiphyseal distraction by external fixator in childhood osteosarcoma was explored. METHODS: Between July 2007 and May 2011, 10 children who were suffering from distal femur osteosarcoma received epiphyseal distraction by external fixator, combined with tumor resection and repair with massive allograft bone to preserve the epiphysis of the distal femur and knee function. There were six male and four female patients, 9- to 14-years old (average 10.5 years old). The tumors were staged clinically according to the Enneking staging method: six cases were classified as stage in IIA and four cases as stage in IIB. All patients were diagnosed by biopsy, then received chemotherapy before and after surgery. All patients received tumor bone resection and the defects of the bone were repaired with massive allograft bone that was fixed by intramedullary nails; the distracted epiphysis and allograft bone were fixed with cancellous screws. RESULTS: All cases received follow-up from 15 to 56 months (average 38.5 months). There were no local recurrences. One case died of lung metastasis and one case had poor incision healing for rejection of allograft bone. According to the functional evaluation criteria of the International Society of Limb Salvage (ISOLS) after operation, five cases were rated excellent, four cases good and one case fair. The ratio of excellent or good was 90.0%. There was no statistically significant difference in length between the operated and the normal lower limbs during the last review. CONCLUSIONS: Epiphyseal distraction by external fixator can result in satisfactory limb length and joint function for children with a malignant bone tumor.

Combination of acellular nerve graft and schwann cells-like cells for rat sciatic nerve regeneration.

OBJECTIVE: To investigate the effect of tissue engineering nerve on repair of rat sciatic nerve defect. METHODS: Forty-five rats with defective sciatic nerve were randomly divided into three groups. Rats in group A were repaired by acellular nerve grafts only. Rats in group B were repaired by tissue engineering nerve. In group C, rats were repaired by autogenous nerve grafts. After six and twelve weeks, sciatic nerve functional index (SFI), neural electrophysiology (NEP), histological and transmission electron microscope observation, recovery ratio of wet weight of gastrocnemius muscle, regenerated myelinated nerve fibers number, nerve fiber diameter, and thickness of the myelin sheath were measured to assess the effect. RESULTS: After six and twelve weeks, the recovery ratio of SFI and wet weight of gastrocnemius muscle, NEP, and the result of regenerated myelinated nerve fibers in groups B and C were superior to that of group A (P < 0.05), and the difference between groups B and C was not statistically significant (P > 0.05). CONCLUSION: The tissue engineering nerve composed of acellular allogenic nerve scaffold and Schwann cells-like cells can effectively repair the nerve defect in rats and its effect was similar to that of the autogenous nerve grafts.

Effects of metaphyseal bone tumor removal with preservation of the epiphysis and knee arthroplasty.

In this study, the effects of surgical removal of malignant metaphyseal bone tumors with epiphysis preservation and knee arthroplasty were analyzed. A total of 15 patients with malignant metaphyseal bone tumors were investigated. Six of these patients underwent epiphyseal preservation surgery with preoperative physeal distraction, termed the physeal distraction (PD) group. Nine patients underwent resection of the knee joint, combined with metal prosthesis transfer, termed the knee arthroplasty (KA) group. Tumor control, limb length discrepancy, range of movement (ROM) of the knee and functional outcome of lower limb [Musculoskeletal Tumor Society (MSTS) score and the Toronto extremity salvage score (TESS)] were assessed for these two groups. All 15 patients were followed-up after the surgery. One patient in the PD group was found to have lung tumor metastasis; however, no local tumor recurrence was found. In the KA group, local tumor recurrence was found in one patient, and lung metastases were observed in two cases postoperatively. The limb length discrepancy in patients of the PD group was 2.58±0.27 cm, which was significantly less compared with that in patients in the KA group (4.01±0.13 cm; P<0.05). In addition, the lower limb knee ROM in patients in the PD group was 127.70±14.63°, which was increased compared to that in patients in the KA group (105.70±15.48°; P<0.05). The mean MSTS score was 86.67% with a mean TESS of 82.33% in patients from the PD group, which showed no significant difference compared with the respective scores for patients in the KA group (P>0.05). Therefore, epiphyseal sparing limb-saving surgeries should be considered for the treatment of malignant metaphyseal bone tumors in children, when certain indications are satisfied.

Comparison of morphology and biocompatibility of acellular nerve scaffolds processed by different chemical methods.

To investigate the morphological differences among acellular rat nerve scaffolds processed by different chemical methods and compare the biocompatibility between rat nerve grafts processed by different chemical methods and rat adipose-derived stem cells in vitro. Acellular rat sciatic nerve scaffolds processed by two different chemical methods (the Sondell method and the optimized method) and normal rat sciatic nerves were used as control. The structure and components of nerve scaffold were observed under microscopy, the degrees of decellularization and demyelination of nerve scaffold and integrity of nerve fiber tubes were assessed. The rat adipose-derived stem cells growth and adherence on scaffold were studied by scanning electron microscopy, the activity and adhesive ratio of rat adipose-derived stem cells in the nerve scaffold were compared. The basal lamina tubes and the extracellular matrix in the epineurium and perineurium in the nerve graft of optimized method were better preserved than the nerve graft of the Sondell method. After co-cultured with scaffolds, the difference of cell activity between three groups (two cell-scaffold combinations and control group) at the same observation time were not statistically significant (P > 0.05),the adhesive ratio of rat adipose-derived stem cells in the scaffold of the optimized method was better than that of the Sondell method. The scaffold of the optimized method is more effective than the scaffold of the Sondell method for peripheral nerve tissue engineering.

TRAF4 enhances osteosarcoma cell proliferation and invasion by Akt signaling pathway.

TRAF4, or tumor necrosis factor receptor-associated factor 4, is overexpressed in several cancers, suggesting a specific role in cancer progression. However, its functions in osteosarcoma are unclear. This study aimed to explore the expression of TRAF4 in osteosarcoma tissues and cells, the correlation of TRAF4 to clinical pathology of osteosarcoma, as well as the role and mechanism of TRAF4 in osteosarcoma metastasis. The protein expression levels of TRAF4 in osteosarcoma tissues and three osteosarcoma cell lines, MG-63, HOS, and U2OS, were assessed. Constructed TRAF4 overexpression vectors and established TRAF4 overexpression of the U2OS cell line. Cell proliferation, cell invasion, protein levels, and TRAF4 phosphorylations were assessed following TRAF4 transfection, as well as the effects of TRAF4 siRNA on cell proliferation and invasion. The results show that TRAF4 protein levels in osteosarcoma tissues were significantly higher than that in normal bone tissues. Importantly, an obvious upregulation of TRAF4 was found in carcinoma tissues from patients with lung metastasis compared with patients without lung metastasis. Consistently, a similar increase in TRAF4 mRNA and protein was also demonstrated in the osteosarcoma cell lines MG-63, HOS, and U2OS compared to normal bone cells, hFOB1.19. When TRAF4 was overexpressed in U2OS cells, cell proliferation was significantly enhanced, accompanied by an increase in Ki67 expression and colony formation. Compared with the control and vector-treated groups, TRAF4 transfection increased the invasion potential of U2OS cells (p < 0.05). Interestingly, TRAF4 transfection significantly enhanced the phosphorylation of Akt. After blocking Akt with its specific siRNA, TRAF4-induced cell proliferation and invasion were dramatically attenuated. In summary, our findings demonstrated that TRAF4 enhances osteosarcoma cell proliferation and invasion partially by the Akt pathway. This work suggests that TRAF4 might be an important target in osteosarcoma.