Daidzein alleviates osteoporosis by promoting osteogenesis and angiogenesis coupling.

Background: Postmenopausal osteoporosis and osteoporosis-related fractures are world-wide serious public health problem. Recent studies demonstrated that inhibiting caveolin-1 leads to osteoclastogenesis suppression and protection against OVX-induced osteoporosis. This study aimed to explore the mechanism of caveolin-1 mediating bone loss and the potential therapeutic target. Methods: Thirty C57BL/6 female mice were allocated randomly into three groups: sham or bilateral ovariectomy (OVX) surgeries were performed for mice and subsequently daidzein or vehicle was administrated to animals (control, OVX + vehicle and OVX + daidzein). After 8-week administration, femurs were harvested for Micro-CT scan, histological staining including H&E, immunohistochemistry, immunofluorescence, TRAP. Bone marrow endothelial cells (BMECs) were cultured and treated with inhibitors of caveolin-1 (daidzein) or EGFR (erlotinib) and then scratch wound healing and ki67 assays were performed. In addition, cells were harvested for western blot and PCR analysis. Results: Micro-CT showed inhibiting caveolin-1with daidzein alleviated OVX-induced osteoporosis and osteogenesis suppression. Further investigations revealed H-type vessels in cancellous bone were decreased in OVX-induced mice, which can be alleviated by daidzein. It was subsequently proved that daidzein improved migration and proliferation of BMECs hence improved H-type vessels formation through inhibiting caveolin-1, which suppressed EGFR/AKT/PI3K signaling in BMECs. Conclusions: This study demonstrated that daidzein alleviates OVX-induced osteoporosis by promoting H-type vessels formation in cancellous bone, which then promotes bone formation. Activating EGFR/AKT/PI3K signaling could be the critical reason.

CCL2 is a critical mechano-responsive mediator in crosstalk between osteoblasts and bone mesenchymal stromal cells.

It has been known that moderate mechanical loading, like that caused by exercise, promotes bone formation. However, its underlying mechanisms remain elusive. Here we showed that moderate running dramatically improved trabecular bone in mice tibias with an increase in bone volume fraction and trabecular number and a decrease in trabecular pattern factor. Results of immunohistochemical and histochemical staining revealed that moderate running mainly increased the number of osteoblasts but had no effect on osteoclasts. In addition, we observed a dramatic increase in the number of colony forming unit-fibroblast in endosteal bone marrow and the percentage of CD45- Leptin receptor+ (CD45- LepR+ ) endosteal mesenchymal progenitors. Bioinformatics analysis of the transcriptional data from gene expression omnibus (GEO) database identified chemokine c-c-motif ligands (CCL2) as a critical candidate induced by mechanical loading. Interestingly, we found that CCL2 was up-regulated mainly in osteoblastic cells in the tibia of mice after moderate running. Further, we found that mechanical loading up-regulated the expression of CCL2 by activating ERK1/2 pathway, thereby stimulating migration of endosteal progenitors. Finally, neutralizing CCL2 abolished the recruitment of endosteal progenitors and the increased bone formation in mice after 4 weeks running. These results therefore uncover an unknown connection between osteoblasts and endosteal progenitors recruited in the increased bone formation induced by mechanical loading.

EGFR/FAK and c-Src signalling pathways mediate the internalisation of Staphylococcus aureus by osteoblasts.

Internalisation of Staphylococcus aureus in osteoblasts plays a critical role in the persistence and recurrence of osteomyelitis, the mechanisms involved in this process remain largely unknown. In the present study, evidence of internalised S. aureus in osteoblasts was found in long bone of haematogenous osteomyelitis in mice after 2 weeks of infection. Meanwhile, eliminating extracellular S. aureus by gentamicin can partially rescue bone loss, whereas the remaining intracellular S. aureus in osteoblasts may be associated with continuous bone destruction. In osteoblastic MC3T3 cells, intracellular S. aureus was detectable as early as 15 min after infection, and the internalisation rates increased with the extension of infection time. Additionally, S. aureus invasion stimulated the expression of phosphor-focal adhesion kinase (FAK), phosphor-epidermal growth factor receptor (EGFR) and phosphor-c-Src in a time-dependent way, and blocking EGFR/FAK or c-Src signalling significantly reduced the internalisation rate of S. aureus in osteoblasts. Our findings provide new insights into the mechanism of S. aureus internalisation in osteoblast and raise the potential of targeting EGFR/FAK and c-Src as adjunctive therapeutics for treating chronic S. aureus osteomyelitis.

Strontium-substituted calcium sulfate hemihydrate/hydroxyapatite scaffold enhances bone regeneration by recruiting bone mesenchymal stromal cells.

Fabrication of osteoconductive scaffold with osteoinductive capability and appropriate resorption rate is of great significance for treating bone defects. To achieve this aim, strontium-substituted calcium sulfate hemihydrate (Sr-CSH) and hydroxyapatite (HA) were mixed to develop a novel composite. Sr-CSH containing 5% and 10% strontium was mixed with HA at the weight ratio of 6:4, respectively. Female Sprague-Dawley rats underwent bone defect surgery in left tibia were randomly assigned to three different treatment groups filled with CSH/HA, 5% and 10% Sr-CSH/HA. Micro-CT analysis showed increased new bone formation in 10% Sr-CSH/HA group compared to CSH/HA group. In addition, histological analysis showed large amounts of chondrocytes and osteoblasts within the pores of Sr-CSH/HA composites as a result of the CSH resorption. Further, CFU-F assay demonstrated the increased amount of bone marrow mesenchymal stromal cells (BMSCs) colonies in 10% Sr-CSH/HA group. In primary BMSCs, extraction from Sr-CSH/HA composite significantly increased the migration of cells, up-regulated the expression of osteoblastic marker genes, and increased the area of mineralized nodules. Together, Sr-CSH/HA may promote bone formation by recruiting and stimulating osteogenic differentiation of BMSCs. Therefore, this composite may be proposed as an ideal substitute to repair bone defects.

High cholesterol induces apoptosis and autophagy through the ROS-activated AKT/FOXO1 pathway in tendon-derived stem cells.

BACKGROUND: Hypercholesterolemia increases the risk of tendon pain and tendon rupture. Tendon-derived stem cells (TDSCs) play a vital role in the development of tendinopathy. Our previous research found that high cholesterol inhibits tendon-related gene expression in TDSCs. Whether high cholesterol has other biological effects on TDSCs remains unknown. METHODS: TDSCs isolated from female SD rats were exposed to 10 mg/dL cholesterol for 24 h. Then, cell apoptosis was assessed using flow cytometry and fluorescence microscope. RFP-GFP-LC3 adenovirus transfection was used for measuring autophagy. Signaling transduction was measured by immunofluorescence and immunoblotting. In addition, Achilles tendons from ApoE -/- mice fed with a high-fat diet were histologically assessed using HE staining and immunohistochemistry. RESULTS: In this work, we verified that 10 mg/dL cholesterol suppressed cell proliferation and migration and induced G0/G1 phase arrest. Additionally, cholesterol induced apoptosis and autophagy simultaneously in TDSCs. Apoptosis induction was related to increased expression of cleaved caspase-3 and BAX and decreased expression of Bcl-xL. The occurrence of autophagic flux and accumulation of LC3-II demonstrated the induction of autophagy by cholesterol. Compared with the effects of cholesterol treatment alone, the autophagy inhibitor 3-methyladenine (3-MA) enhanced apoptosis, while the apoptosis inhibitor Z-VAD-FMK diminished cholesterol-induced autophagy. Moreover, cholesterol triggered reactive oxygen species (ROS) generation and activated the AKT/FOXO1 pathway, while the ROS scavenger NAC blocked cholesterol-induced activation of the AKT/FOXO1 pathway. NAC and the FOXO1 inhibitor AS1842856 rescued the apoptosis and autophagy induced by cholesterol. Finally, high cholesterol elevated the expression of cleaved caspase-3, Bax, LC3-II, and FOXO1 in vivo. CONCLUSION: The present study indicated that high cholesterol induced apoptosis and autophagy through ROS-activated AKT/FOXO1 signaling in TDSCs, providing new insights into the mechanism of hypercholesterolemia-induced tendinopathy. High cholesterol induces apoptosis and autophagy through the ROS-activated AKT/FOXO1 pathway in tendon-derived stem cells.

[Analysis of Clinical Characteristics of Acute B Lymphoblastic Leukemia with EP300-ZNF384 Fusion Gene Positive].

OBJECTIVE: To investigate the clinical manifestations and laboratory features of B-ALL patients with EP300-ZNF384 fusion gene positive, so as to improve the understanding of this subtype disease. METHODS: The clinical data of 3 B-ALL patients with EP300-ZNF384 fusion gene positive admitted in Department of Hematology, the first medical center of Chinese PLA general hospital from February 2017 to February 2018 were collected and analyzed retrospectively. The clinical and laboratory characteristics as well as the therapentic outcome in B-ALL patients with EP300-ZNF384 fusion gene positive were analyzed. RESULTS: The fusion gene of EP300-ZNF384 was detected in 8.1%(3/37) of B-ALL patients. All cases showed the normal karyotype and aberrant CD13 and/or CD33 expression for immunophenotype. 3 patients were sensitive to traditional chemotherapy. CONCLUSION: The B-ALL with EEP300-ZNF384 fusion gene positive may be a subgroup of B-ALL with a uniqe clinical characteristis and laboatorial features. EP300-ZNF384 positive patients show a good response to conventional chemotherapy, suggesting a favorable prognosis.

Aucubin Protects Chondrocytes Against IL-1ß-Induced Apoptosis In Vitro And Inhibits Osteoarthritis In Mice Model.

OBJECTIVE: Chondrocyte apoptosis has also been strongly correlated with the severity of cartilage damage and matrix depletion in an osteoarthritis (OA) joint. Therefore, pharmacological inhibitors of apoptosis may provide a novel treatment option for patients with OA. Aucubin, a natural compound isolated from Eucommia ulmoides, has been proved to possess antioxidative and anti-apoptotic properties. However, anti-osteoarthritis effect of aucubin in animal model and anti-apoptotic response of aucubin in OA chondrocytes remain unclear. This study aimed to determine whether aucubin could slow progression of OA in a mouse model and inhibit the IL-1ß-induced chondrocyte apoptosis. METHODS: OA severity and articular cartilage degradation were evaluated by Safranin-O staining, Hematoxylin-eosin (H&E) staining, and Osteoarthritis Research Society International (OARSI) standards. Chondrocyte viability was observed by Cell Counting Kit-8 (CCK8) and live/dead cells assay; the apoptotic rate of chondrocytes was evaluated by flow cytometry (FCM) with Annexin V-FITC/PI kit. Mediators of apoptosis were tested by Western blot of Bax, caspase-3, caspase-9, and Bcl-2 expression. The intracellular levels of Reactive oxygen species (ROS) were assessed by the probe of 2,7-Dichlorofluorescin diacetate (DCFH-DA). RESULTS: The articular cartilage in the limb with destabilization of the medial meniscus (DMM) exhibited early OA-like manifestations characterized by proteoglycan loss, cartilage fibrillation, and erosion, with lower OARSI score. Oral administration of aucubin remarkably attenuated the loss of proteoglycan and the articular cartilage erosion and decreased the OARSI scores underwent DMM surgery. Aucubin treatment significantly reverses IL-1ß-induced cytotoxicity and attenuated the IL-1ß-induced chondrocyte apoptosis. In addition, aucubin can significantly inhibit mediators of apoptosis in rat primary chondrocytes. Furthermore, aucubin remarkably attenuated the IL-1ß-induced intracellular ROS production. CONCLUSION: Our findings suggest that aucubin has a protective effect on articular cartilage and slowing progression of OA in a mouse model. This protective effect may result from inhibiting chondrocyte apoptosis and excessive ROS production.

[Clinical Retrospective Analysis of Chronic Myeloid Leukemia in Myeloid Blast Crisis].

OBJECTIVE: To retrospectively analyze the clinical manifestation, laboratorial test features and prognosis of patients with CML in myeloid blast crisis. METHODS: The clinical data of 10 patients with CML in myeloid blast crisis admitted in Chinese PLA General Hospital from June 2011 to May 2018 were collected, and their clinical features, laboratorial data and long-term survival were analyzed. RESULTS: The median age of these 10 cases was 32.5 (23-73) years old. Nine cases had chronic phase history. The median chronic phase was 17(4-84) months. All the 10 cases had splenomegaly; B-ultrasonography showed that the median spleen size was 5.2 (4-7.8) cm in thickness, and 14.6 (11.4-19.8) in length. When chronic myeloid leukemia was in blast crisis, the median WBC count was 41.705（11.9-344.41）×109 /L and the median platelet count was 159 (13-2326) ×109 /L. The Ph+ chromosome and BCR-ABL1 fusion gene coulld be detected in all the cases. The chromosome karyotyping showed that additional chromosome abnormalities were found in 5 cases. One case was of low diploid, and two cases were with complex karyotype. ABL1 mutation was detected in 6 out of these 10 cases. ABL1 T315I mutation was detected in 2 of them and one was with deletion of combined P53 in genetic tests. The median follow-up time was 10.5(0.2-78) months. There were 5 cases treated sequentially by chemotheraphy with or without TKI and allo-HSCT. Three cases reached CP2 before transplantation. Among them, two cases still survived without progression for 67 months and 69 months after the transplantation respectively. One case died of transplantation-related mortality (suffered from cerebral hemorrhage 7 months after the transplantation). Two cases were NR before the transplantation, and both died of disease relapse or progression at the time points of one or three months after the transplantation. Five cases treated by TKI ± chemotheraphy and without HSCT succumbed to disease progression. The median time was 6(0.2-22) months. CONCLUSION: CML patients in myeloid blast crisis treated by chemotheraphy combined with TKI gain CP2, the survival time of patients treated by sequential allo-HSCT is prolonged.

Reduced PDGF-AA in subchondral bone leads to articular cartilage degeneration after strenuous running.

To identify the effects of running on articular cartilage and subchondral bone remodeling, C57BL/6 mice were randomly divided into three groups: control, moderate-, and strenuous running. Magnetic resonance imaging showed bone marrow lesions in the knee subchondral bone in the strenuous-running group in contrast with the other two groups. The microcomputed tomography analysis showed promoted bone formation in the subchondral bone in mice subjected to strenuous running. Histological and immunohistochemistry results indicated that terminal differentiation of chondrocytes and degeneration of articular cartilage were enhanced but, synthesis of platelet-derived growth factor-AA (PDGF-AA) in the subchondral bone was suppressed after strenuous running. In vitro, excessive mechanical treatments suppressed the expression of PDGF-AA in osteoblasts, and the condition medium from mechanical-treated osteoblasts stimulated maturation and terminal differentiation of chondrocytes. These results indicate that strenuous running suppresses the synthesis of PDGF-AA in subchondral bone, leading to downregulated PDGF/Akt signal in articular cartilage and thus cartilage degeneration.

Clinical characteristics and treatment of clavicular osteomyelitis: a systematic review with pooled analysis of 294 reported cases.

BACKGROUND: It is usually difficult to diagnose clavicular osteomyelitis (OM), and treatment is delayed because of its rarity. This study aimed to summarize clinical characteristics and treatment of this disease. METHODS: We searched the PubMed and Embase databases to identify English studies that reported on clavicular OM from January 1980 through December 2016. Effective data were pooled for analysis. RESULTS: In total, 111 studies comprising 294 cases (bacterial OM, 146; nonbacterial OM, 148) were included, with a sex ratio of 1.89:1 indicating female predilection. Overall, the median age at diagnosis was 16 years. The acute to chronic phase ratio was 0.30, with a median symptom duration of 4 months. The most frequently reported symptom was pain (192 cases), followed by swelling (151 cases) and fever (52 cases). Altogether, 86.94% cases of single-site involvement were reported, with the medial side being the most common site (69.95%). The erythrocyte sedimentation rate achieved the highest positive rate (74.44%) before treatment. The total positive rate of culture for bacterial OM was 81.82%, with Staphylococcus aureus being the most frequently detected pathogen (44.70%). The average cure rate was 83.52%, with no significant difference between surgical (89.70%) and nonsurgical (79.63%) cases (P = .079). CONCLUSIONS: Clavicular OM, predominant in female patients and young people, usually occurred at a chronic stage. Pain was the most frequent symptom, with the medial side being the most involved site. The erythrocyte sedimentation rate may be a helpful indicator for diagnosis. Regardless of surgery or nonsurgery, most patients achieved a favorable prognosis.

Screening of TNF-α gene polymorphisms in patients with extremity chronic osteomyelitis in China.

AIM: This study aims to investigate the link between TNF-α gene SNPs and patients with extremity chronic osteomyelitis in China. METHODOLOGY: Our study included 433 subjects, composed of 233 extremity chronic osteomyelitis patients and 200 controls. Six single-nucleotide polymorphisms (rs1799964, rs1800630, rs1799724, rs1800750, rs1800629 and rs361525) in TNF-α gene were detected by the SNaPshot genotyping method. RESULTS: Significant genotype distribution of rs1799964 was identified between patients and healthy controls (p = 0.045). In addition, statistical difference was found between rs1799964 SNP and the susceptibility to extremity chronic osteomyelitis (p = 0.044). CONCLUSION: We reported for the first time that TNF-α gene SNP rs1799964 contributes to the elevated venture of extremity chronic osteomyelitis in China.

Lateral Subcutaneous Locking Compression Plate and Small Incision Reduction for Distal-third Diaphyseal Humerus Fractures.

OBJECTIVE: Iatrogenic radial nerve injury is a great challenge for orthopaedic surgeons who deal with distal-third diaphyseal humerus fractures. Conventional open reduction and internal fixation (ORIF) remains the gold standard, but complications such as nonunion and iatrogenic radial nerve injury still occur. We fixed the fractures with a lateral locking compression plate (LCP) subcutaneously after small incision reduction to protect the radial nerve. This study reports the clinical and radiographic outcomes of our modified method. METHODS: Thirty-eight patients with distal-third diaphyseal humerus fractures were treated with lateral subcutaneous LCP and small incision reduction at our department between September 2013 and August 2016. There were 33 males and 5 females, with an average age of 30.3 years (range, 17 to 49 years). All the cases were types A or B (AO/OTA classification, type A, 24 cases; type B, 14 cases). Among them, 6 cases were combined with preoperative radial nerve palsy. All patients were diagnosed with closed humeral fractures after X-ray examination, and had typical upper limb pain, swelling, and movement disorders. The operations were performed by a single surgeons' team. Union time, range of motion (ROM), University of California, Los Angeles (UCLA) shoulder rating scale, and Mayo Elbow Performance Index (MEPI) scores were assessed to evaluate the postoperative results. RESULTS: All patients were followed up for an average of 11.4 months (range, 3 to 36 months). The average operation time was 75.5 min (range, 60 to 150 min) and average intraoperative radiation exposure was 10.5 s (range, 8 to 18 s). Bony union was achieved in all cases after an average of 16.2 weeks (range, 12 to 25 weeks). No complications such as infection or screw and plate fracture occurred, and no iatrogenic radial nerve injury was observed. According to the UCLA shoulder rating scale, the average score was 33.7 (range, 31 to 35), with 33 excellent (86.8%) and 5 good cases (13.2%). They were all excellent according to their MEPI scores (ranging, 94 to 100, with an average of 97.4). The average operation time for secondary removal of the plate was 15.2 min (range, 10 to 20 min), and no complications such as infection or secondary radial nerve injury occurred. CONCLUSIONS: Lateral subcutaneous LCP and small incision reduction may reduce the risk of iatrogenic radial nerve injury significantly in the treatment of distal-third diaphyseal humerus fractures. It also leads to solid fixation, good postoperative function, and convenient removal of the plate without injuring the radial nerve.

Differentially Expressed Genes in Osteomyelitis Induced by Staphylococcus aureus Infection.

Osteomyelitis (OM) is a complicated and serious disease and its underlying molecular signatures of disease initiation and progression remain unclear. Staphylococcus aureus (S. aureus) is the most common causative agent of OM. Previous study of Banchereau et al. has established a link between whole blood transcription profiles and clinical manifestations in patients infected with S. aureus. However, the differentially expressed genes (DEGs) in OM induced by S. aureus infection have not been intensively investigated. In this study, we downloaded the gene expression profile dataset GSE30119 from Gene Expression Omnibus, and performed bioinformatic analysis to identify DEGs in S. aureus infection induced OM from the transcriptional level. The study consisted of 143 whole blood samples, including 44 healthy controls, 42 OM-free, and 57 OM infection patients. A total of 209 S. aureus infection-related genes (SARGs) and 377 OM-related genes (OMRGs) were identified. The SARGs were primarily involved in the immune response by GO functional and pathway enrichment analysis. Several proteins adhere to neutrophil extracellular traps may be critical for the immune response to the process of S. aureus infection. By contrast, the OMRGs differ from the SARGs. The OMRGs were enriched in transmembrane signaling receptor and calcium channel activity, cilium morphogenesis, chromatin silencing, even multicellular organism development. Several key proteins, including PHLPP2 and EGF, were hub nodes in protein-protein interaction network of the OMRGs. In addition, alcoholism, systemic lupus erythematosus and proteoglycans in cancer were the top pathways influenced by the OMRGs associated with OM. Thus, this study has further explored the DEGs and their biological functions associated with S. aureus infection and OM, comparing with the previous study, and may light the further insight into the underlying molecular mechanisms and the potential critical biomarkers in OM development.

[Safety and Effectiveness of High Dose Tigecycline for Treating Patients with Acute Leukemia after Ineffctiveness of Carbapenems Chemotherapy Combinating with Febrile Neutropenia: Retrospective study].

OBJECTIVE: To investigate the safety and efficacy of high dose tigecycline for treatment of fibric neutrope-nia in acute leukemia patients after ineffectiveness of carbapenems chemotherapy of acute leukemia. METHODS: The clinical data of 41 acute leukemia patients with febrile ncutropenia received high dose tigecycline (100 mg q12h), who showed ineffectiveness of treatment with carbapenems, from 20151.30-2017.1. 29 in our hospital were collected and analyzed retrospectively. The temperature, inflammatory indicators as well as hepatic and renal function before and after treatment with tigecycline were compared. RESULTS: Among 41 patients treated with tigecycline due to ineffectiveness of treatment with carbapenems, the infection had been controled in 34 cases, 7 patients died due to ineffectiveness of anti-infective treatment, these patients all were patients with relapse/refractory leukemia. 41 patients were examined etialogically, as a result, 22 patients showed possitive, among them the gram-negative bacill was found in 11(11/22) cases. The average deferves counce time of tigecycline was 28.2±12.0 hours. The temperature of patients treated with tigecycline for 48 hours decreased significantly (P<0.05). There were no significant differences in calcitonin and C-reactive protein levels after treatment with tigecycline (P>0.05), but cacitonin level displayed decrease tread. There was no hepatic and renal impairment after treatment with tigecycline, but levels of as partate aminotransferase, total bilirubin and blood area nitrogen in blood significantly increased as compared with levels before treatment with tigecycline (P<0.05). CONCLUSION: The application of high dose tigecycline for treatment of febrile neutropenia is safety and effective. The high dose tigecycline can decrease the temperature, calcitonin and C-reactive protein levels, and can control infection without the hepatic and renal impairment, but it needs to be confimed by more prospective studies.

Decitabine-based chemotherapy followed by haploidentical lymphocyte infusion improves the effectiveness in elderly patients with acute myeloid leukemia.

In this study, we first initiated a multicenter, single-arm, phase-II clinical trial using decitabine (DAC) (20mg/m2 for five days) based chemotherapy, followed by haploidentical lymphocyte infusion (HLI) that was applied as induction therapy for elderly patients with AML. Furthermore, the role of HLI infusion was explored in a mouse model. The clinical trial included 29 elderly patients (median age: 64, range 57-77) with AML. Sixteen cases achieved complete remission (CR) and 9 cases achieved partial remission (PR) after the first treatment cycle. Of the patients with PR, 5 subjects achieved remission after the second induction, which brings the overall CR rate to 72.4%. The 2-year overall survival (OS) and disease-free survival (DFS) was 59.6% and 36.9% respectively. The treatment regimen was well tolerated with only one patient died of severe pneumonia one month after the first treatment. In the mouse experiment, we found that DAC/HLI significantly enhanced the survival of leukemic mice. These results suggested that DAC-based chemotherapy combined with HLI is an alternative first line induction therapy for elderly patients with AML. This trial is registered at ClinicalTrials.gov (NCT01690507).

[Retrospective Study of Ph+/BCR-ABL+ Acute Myelogenous Leukemia].

OBJECTIVE: To investigate the clinical manifestation, features of laboratorial examination results and prognosis of patients with Ph+/BCR-ABL+ acute myelogenous leukemia(AML). METHODS: The clinical data of 5 AML patients with Ph+/BCR-ABL+ admitted in Department of Hematology of Chinese PLA general hospital from July 2007 to May 2015 were collected and their clinical characteristics, laboatorial examination results and long-term survival were analyzed. RESULTS: The median age of 5 cases was 39 years old, and 2 cases with splenomegaly. All the cases were assayed for BCR-ABL fusion gene, and 2 of them were accompanied with other molecular abnormalities. In 4 cases, Ph chromosome was not found in one case, and one was with complex karyotype. 3 cases still are live till now and are treated by traditional chemotherapy combined with TKI, and consolidated by allo-HSCT. One case treated by traditional chemotherapy survived for 6 months. And one case treated by traditional chemotherapy combined with TKI survives till to now. CONCLUSION: The survival time of Ph+/BCR-ABL+ acute myelogenous leukemia is improved by the traditional chemotherapy combined with TKI and the consolidation with allo-HSCT.

Assessment of fracture risk in proximal tibia with tumorous bone defects by a finite element method.

There has not been a satisfying method to predict the fracture risk in tumorous bone lesions. To tackle this challenge, we used a finite element method to assess the fracture risk in the proximal tibia (pT) when the size and location of the tumorous defects are varied in bone. Towards this end, the circular cortical defects, mimicking the tumorous lesions by forming cortical window defects, with a diameter (Ф) of 20, 30, 40, or 50 mm, are structured on the anteromedial, lateral, posterior wall of pT, which is located 5, 15, and 25 mm below articular margin, respectively. We found that under walking conditions, the Von Mises Stress of each defective tibia model was larger than that of the intact tibia model and also showed a positive linear correlation with the sizes of the defects. A notable fracture risk was not observed until the defect was Ф30 mm or larger. When the defect emerged, the anteromedial wall resisted fracture risk more than the rest of wall. Our results show that the size and location of the bone tumors are important factors affecting the fracture risk of pT. Our findings will be beneficial to clinicians when deciding what treatment to use for pT lesions.

Correlation Between Isocitrate Dehydrogenase Gene Aberrations and Prognosis of Patients with Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis.

Purpose: Whether isocitrate dehydrogenase (IDH) gene aberrations affected prognosis of patients with acute myeloid leukemia (AML) was controversial. Here, we conducted a meta-analysis to evaluate their prognostic value.Experimental Design: PubMed, Embase, Cochrane, and Chinese databases were searched to identify studies exploring how IDH gene aberrations affected AML outcome. Pooled HRs and relative risks (RR) were calculated, along with 95% confidence intervals (CI).Results: Thirty-three reports were included. IDH mutations seemed not to affect overall survival (OS: HR, 1.05; 95% CI, 0.89-1.23) and event-free survival (EFS: HR, 0.97; 95% CI, 0.80-1.18) when considered as a single factor, but improved accumulative incidence of relapse (CIR: HR, 1.44; 95% CI, 1.18-1.76) in patients with intermediate-risk karyotypes (IR-AML). However, IDH1 mutation conferred worse OS (HR, 1.17; 95% CI, 1.05-1.31) and EFS (HR, 1.29; 95% CI, 1.07-1.56), especially in patients with normal cytogenetics (OS: HR, 1.21; 95% CI, 1.01-1.46; EFS: HR, 1.56; 95% CI, 1.23-1.98). Prognosis of the IDH1 single-nucleotide polymorphism rs11554137 was also poor (OS: HR, 1.34; 95% CI, 1.03-1.75). IDH2 mutation improved OS (HR, 0.78; 95% CI, 0.66-0.93), particularly in IR-AML patients (OS: HR, 0.65; 95% CI, 0.49-0.86). The IDH2 (R140) mutation was associated with better OS among younger cases (HR, 0.64; 95% CI, 0.49-0.82). Treatment outcome was poor [RR for complete remission rates in IDH1 mutation: 1.21; 95% CI, 1.02-1.44; IDH2 (R172) mutation: 2.14; 95% CI, 1.61-2.85].Conclusions: Various subtypes of IDH mutations might contribute to different prognosis and be allowed to stratify IR-AML further. Clin Cancer Res; 23(15); 4511-22. ©2017 AACR.

Clinical Significance of a Novel Knee Joint Stability Assessment System for Evaluating Anterior Cruciate Ligament Deficient Knees.

OBJECTIVE: To investigate the six degrees of freedom (6DOF) kinematics of anterior cruciate ligament (ACL) deficient knees during gait and to explore the clinical significance of a novel knee joint stability assessment system (Opti_Knee, Innomotion, Shanghai, China) in comparison with imaging and arthroscopic examination. METHODS: Three subjects diagnosed with ACL deficient knees on the basis of preoperative MRI and CT findings were subjected to treadmill gait analysis. Motion of both knees in 6DOF was measured and analyzed with an optical joint kinematics measurement system. Arthroscopic examination, the gold standard, was performed to confirm the final diagnosis and the clinical diagnosis of ACL deficiency by imaging and motion marker techniques compared with this gold standard. RESULTS: Only two of the three subjects diagnosed with ACL deficiency by imaging techniques were later confirmed to have this condition by arthroscopic examination; the third was found to have an intact ACL. When the kinematics of their injured and contralateral knees were compared, abnormalities were found in the two subjects confirmed by arthroscopy to be ACL deficient However, no kinematic difference between the two knees was found in the ACL intact subject. CONCLUSIONS: Opti_Knee (Innomotion) can detect abnormal kinematics in ACL deficient knees and thus provides an effective way of assisting the diagnosis of this condition and has potential for clinical application.

Clinical examination of anterior cruciate ligament rupture: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this study was to evaluate the sensitivity and specificity of 3 tests for assessing anterior cruciate ligament (ACL) ruptures. METHODS: MEDLINE, EMBASE, Cochrane Library, and CBM (Chinese Biomedical Literature Database) searches were performed. Studies selected for data extraction were those that addressed the accuracy of at least 1 physical diagnostic test for ACL rupture in comparison with a clinical reference standard such as arthroscopy, arthrotomy, or magnetic resonance imaging (MRI). The references of the included studies were also reviewed. Searches were limited to English and Chinese languages. RESULTS: Sixteen studies that assessed the accuracy of the 3 tests for diagnosing ACL ruptures met the inclusion criteria. Study results were, however, heterogeneous. The Lachman test is the most sensitive test to determine ACL tears, showing a pooled sensitivity of 87.1% (95% confidence interval [CI] 0.84-0.90). The pivot shift test is the most specific test, showing a pooled specificity of 97.5% (95% CI 0.95-0.99); additionally, it has the highest positive likelihood ratios (LR+) of 16.00 (95% CI 7.34-34.87). The Lachman test has the lowest negative likelihood ratios (LR-) of 0.17 (95% CI 0.11-0.25). CONCLUSION: In cases of suspected ACL injury, it is recommended to perform the pivot shift test, as it is highly specific and has greater likelihood and discrimination of accurately diagnosing ACL rupture. The Lachman test has great efficacy in ruling out a diagnosis of ACL rupture because of the lowest negative likelihood ratios.