Yue Xie

Risk factors for postoperative complication after spinal fusion and instrumentation in degenerative lumbar scoliosis patients

BackgroundRelatively few studies have focused on the major medical complications that are more common in older adults. Furthermore, these studies have generally not reported how accurately a risk factor, or combination of risk factors, can distinguish between those who will have a complication and those who will not.MethodsA total of 236 consecutive patients who had undergone surgical treatment for degenerative lumbar scoliosis between June 2008 and June 2012 were included retrospectively in this study. The demographic distribution, medical history, and clinical data were collected to investigate the predictive factors of postoperative complications by logistic regression.ResultsAmong 236 eligible patients, major medical complications occurred in 7.2% of cases and wound complications occurred in 1.7% of cases. Ninety-day mortality rate was 0.4%. Postoperative complications were strongly associated with history of severe chronic obstructive pulmonary disease (COPD) (P = 0.031), dyspnea with minimal exertion (P = 0.041), being at least partially dependent (P = 0.041), smoking within the past year (P = 0.044), American Society of Anesthesiologists (ASA) class of more than 2 (P = 0.000), diabetes treated with insulin (P = 0.003), and steroid use for chronic condition (P = 0.003). In logistic regressions, operation time (odds ratio 2.45, 95% confidence interval 1.11–4.78), ASA class (class 3 or 4 vs. class 1 or 2: odds ratio 2.21, 95% confidence interval 1.22–3.45), insulin-dependent diabetes (odds ratio 1.72, 95% confidence interval 1.18–2.43), and steroid use for chronic condition (odds ratio 1.55, 95% confidence interval 1.06–2.32) may be reasonable predictors for an individuals likelihood of surgical complications.ConclusionsThe occurrence of postoperative complications is most likely multifactorial and is related to operation time, ASA class, insulin-dependent diabetes and steroid use for chronic condition.

K6PC-5, a novel sphingosine kinase 1 (SphK1) activator, alleviates dexamethasone-induced damages to osteoblasts through activating SphK1-Akt signaling

Long-term glucocorticoid usage is a common cause of non-traumatic femoral head osteonecrosis. Glucocorticoids (i.e. dexamethasone (Dex)) could directly induce damages to osteoblasts. In the current study, we investigated the potential activity of K6PC-5 [N-(1,3-dihydroxyisopropyl)-2-hexyl-3-oxo-decanamide], a novel sphingosine kinase 1 (SphK1) activator, against this process. Our data revealed that both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts were responsible to K6PC-5. K6PC-5 activated SphK1, increased sphingosine-1-phosphate (S1P) production and induced Akt phosphorylation in cultured osteoblasts. Functionally, K6PC-5 protected osteoblasts from Dex-induced apoptosis and necrosis. Such signaling and functional effects by K6PC-5 were prevented by the SphK1 inhibitor N,N-dimethylsphingosine (DMS), and by SphK1-siRNAs. On the other hand, exogenously-added S1P activated Akt and reduced Dex-induced osteoblast damages. LY294002 and MK-2206, two established Akt inhibitors, alleviated K6PC-5- or S1P-mediated osteoblast protection against Dex. Together, our results suggest that K6PC-5 alleviates Dex-induced osteoblast injuries through activating SphK1-Akt signaling. K6PC-5 might be further investigated in animal or clinical studies for its anti-glucocorticoids-associated osteonecrosis potential.

α-Melanocyte stimulating hormone attenuates dexamethasone-induced osteoblast damages through activating melanocortin receptor 4-SphK1 signaling

Long-term glucocorticoid (GC) usage may cause non-traumatic femoral head osteonecrosis. Dexamethasone (Dex) is shown to exert potent cytotoxic effect to osteoblasts. Here, we investigated the potential activity of α-melanocyte stimulating hormone (α-MSH) against the process. Our data revealed that pretreatment of α-MSH significantly inhibited Dex-induced apoptosis and necrosis in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. Melanocortin receptor 4 (MC4R) acts as the receptor of α-MSH in mediating its actions in osteoblasts. The MC4R antagonist SHU9119, or shRNA-mediated knockdown of MC4R, almost abolished α-MSH-induced activation of downstream signalings (Akt and Erk1/2) and its pro-survival effect in osteoblasts. Further studies showed that α-MSH activated MC4R downstream sphingosine kinase 1 (SphK1) and increased cellular sphingosine-1-phosphate (S1P) content in MC3T3-E1 cells and primary murine osteoblasts, which were blocked by SHU9119 or MC4R shRNAs. SphK1 inhibition by the its inhibitor N,N-dimethylsphingosine (DMS), or SphK1 knockdown by targeted-shRNAs, largely attenuated α-MSH-mediated osteoblast protection against Dex. Together, these results suggest that α-MSH alleviates Dex-induced damages to cultured osteoblasts through activating MC4R-SphK1 signaling.

MHY1485 activates mTOR and protects osteoblasts from dexamethasone.

Dexamethasone (Dex) exerts cytotoxic effects to cultured osteoblasts. The potential effect of MHY1485, a small-molecular mammalian target of rapamycin (mTOR) activator, against the process was studied here. In both osteoblastic MC3T3-E1 cells and primary murine osteoblasts, treatment with MHY1485 significantly ameliorated Dex-induced cell death and apoptosis. mTOR inhibition, through mTOR kinase inhibitor OSI-027 or mTOR shRNAs, abolished MHY1485-mediated osteoblast cytoprotection against Dex. Intriguingly, activation of mTOR complex (mTORC1), but not mTORC2, is required for MHY1485s anti-Dex activity. mTORC1 inhibitors (rapamycin and RAD001) or Raptor knockdown almost reversed MHY1485-induced osteoblast cytoprotection. mTORC2 inhibition, via shRNA knockdown of Rictor, failed to affect MHY1485s activity in MC3T3-E1 cells. Further studies showed that MHY1485 treatment in MC3T3-E1 cells and primary murine osteoblasts significantly inhibited Dex-induced mitochondrial death pathway activation, the latter was tested by mitochondrial depolarization, cyclophilin D-ANT-1 association and cytochrome C cytosol release. Together, these results suggest that MHY1485 activates mTORC1 signaling to protect osteoblasts from Dex.

Icariside II activates EGFR-Akt-Nrf2 signaling and protects osteoblasts from dexamethasone

The potential effect of icariside II on dexamethasone-induced osteoblast cell damages was evaluated here. In MC3T3-E1 osteoblastic cells and the primary murine osteoblasts, co-treatment with icariside II dramatically attenuated dexamethasone- induced cell death and apoptosis. Icariside II activated Akt signaling, which is required for its actions in osteoblasts. Akt inhibitors (LY294002, perifosine and MK-2206) almost abolished icariside II-induced osteoblast cytoprotection against dexamethasone. Further studies showed that icariside II activated Nrf2 signaling, downstream of Akt, to inhibit dexamethasone-induced reactive oxygen species (ROS) production in MC3T3-E1 cells and primary osteoblasts. On the other hand, Nrf2 shRNA knockdown inhibited icariside II-induced anti-dexamethasone cytoprotection in MC3T3-E1 cells. Finally, we showed that icariside II induced heparin-binding EGF (HB-EGF) production and EGFR trans-activation in MC3T3-E1 cells. EGFR inhibition, via anti-HB-EGF antibody, EGFR inhibitor AG1478 or EGFR shRNA knockdown, almost blocked icariside II-induced Akt-Nrf2 activation in MC3T3-E1 cells. Collectively, we conclude that icariside II activates EGFR-Akt-Nrf2 signaling and protects osteoblasts from dexamethasone. Icariside II might have translational value for the treatment of dexamethasone-associated osteoporosis/osteonecrosis.

Comparison between posterior dynamic stabilization and posterior lumbar interbody fusion in the treatment of degenerative disc disease: a prospective cohort study

BackgroundFew studies compared radiographic and clinical outcomes between posterior dynamic stabilization (PDS) and posterior lumbar intervertebral fusion (PLIF) in treating degenerative disc disease (DDD).MethodsA total of 176 consecutive patients who underwent posterior instrumented spinal surgery for degenerative disc disease between January 2007 and January 2009 were prospectively divided into two groups—PDS and PLIF. All patients included in the analysis were followed up for 3 years. Demographic distribution, perioperative complications, and radiographic and clinical outcomes were compared between the two groups.ResultsThe amount of intraoperative blood loss and drained volume was significantly greater in the PLIF group compared with the PDS group (881.1 ml versus 737.4 ml, p = 0.004). The length of stay of patients who had PLIF surgery (20.9 days) was significantly longer (p = 0.033) than that of patients who underwent PDS surgery (18.9 days). Patients with PLIF surgery had higher total costs than those with PDS surgery (US

RBEL1 is required for osteosarcoma cell proliferation via inhibiting retinoblastoma 1

12826.8 versus US

Activation of Nrf2 by MIND4-17 protects osteoblasts from hydrogen peroxide-induced oxidative stress

11654.5, p = 0.002). No statistically significant differences existed in back visual analogue scale (VAS), leg VAS, or Oswestry disability index (ODI) scores between the PDS and PLIF groups of patients at each time point.ConclusionsCompared with PLIF, PDS have advantages on blood loss, length of stay in hospital, total charges, and radiographic outcomes, but no advantages on leg and back VAS or ODI scores. High-quality randomized controlled trials are still required in the future.

Activating AMP-activated protein kinase by an α1 selective activator compound 13 attenuates dexamethasone-induced osteoblast cell death.

Osteosarcoma is the most common type of primary malignant tumor of the bone. However, mechanisms underlying osteosarcoma cell proliferation are poorly understood. The present study shows that RBEL1, a newly identified Rab-like GTPase, may be a key regulator of osteosarcoma cell proliferation. Knockdown of RBEL1 in osteosarcoma cells resulted in impaired colony formation and cell proliferation. Cell cycle analysis suggested that RBEL1 depletion induced G1-S arrest in osteosarcoma cells. Furthermore, it was demonstrated that retinoblastoma 1 (Rb) was upregulated and activated following RBEL1 knockdown. In addition, Rb inhibitory downstream targets, such as cyclin A2, cyclin D1, c-Myc and cyclin-dependent kinase 2, were downregulated. Rb knockdown reversed RBEL1 depletion-induced tumor suppressive effects. In conclusion, the present results suggest that RBEL1 modulates cell proliferation and G1‑S transition by inhibiting Rb in osteosarcoma. These results suggest a potential therapeutic target in osteosarcoma.

Intrinsic and extrinsic risk factors for nonunion after nonoperative treatment of midshaft clavicle fractures.

MIND4-17 is a recently developed NF-E2-related factor 2 (Nrf2) activator, which uniquely causes Nrf2 disassociation from Keap1. Here, we showed that pretreatment with MIND4-17 significantly inhibited hydrogen peroxide (H2O2)-induced viability reduction of primary osteoblasts and OB-6 osteoblastic cells. Meanwhile, MIND4-17 inhibited both apoptotic and non-apoptotic osteoblast cell death by H2O2. MIND4-17 treatment induced Keap1-Nrf2 disassociation, causing Nrf2 stabilization, accumulation and nuclear translocation in osteoblasts, leading to transcription of several Nrf2-dependent genes, including heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), γ-glutamylcysteine synthetase modifier subunit (GCLM) and catalytic subunit (GCLC). Additionally, MIND4-17 largely attenuated H2O2-reactive oxygen species (ROS) production, lipid peroxidation and DNA damages. Nrf2 knockdown by targeted short hairpin RNA (shRNA) exacerbated H2O2-induced cytotoxicity in OB-6 osteoblastic cells, and nullified MIND4-17-mediated cytoprotection against H2O2. Meanwhile, Keap1 shRNA took over MIND4-17′s actions and protected OB-6 cells from H2O2. Together, MIND4-17 activates Nrf2 signaling and protects osteoblasts from H2O2.