Application of Kirschner wire placement guided technology in paediatric supracondylar humerus fractures.

BACKGROUND: To analyze the clinical efficacy of K-wire placement guided technology in paediatric supracondylar humerus fractures. METHODS: A retrospective study was conducted in 105 patients who underwent closed reduction and percutaneous pinning surgeries in our hospital from June 2019 to August 2022. 54 patients treated with a assisted reduction fixation device to assist in closed reduction and percutaneous K-wire cross-fixation were allocated into the Non-guided group, and 51 patients with K-wire placement guided technology to guide K-wire placement were assigned into the Guided group. The operation duration, number of disposable K-wire placement, intraoperative fluoroscopy frequency, Baumann angle, carrying angle, fracture healing time and Flynn score of elbow joint function at the final follow-up were compared between two groups. The postoperative complications of two groups were recorded. RESULTS: There were significant differences between two groups in terms of operation duration, intraoperative fluoroscopy frequency, and disposable K-wire placement rate (p < 0. 05), while no significant differences of Baumann angle, carrying angle and the fracture healing time between two groups were observed (p > 0. 05). In the control group, ulnar nerve injury in 2 case, pin site infection in 4 cases, mild cubitus varus in 2 cases and loss of reduction in 4 cases were detected. In the study group, ulnar nerve injury in 1 case, pin site infection in 2 cases and loss of reduction in 1 case was observed. There was no significant difference in Flynn scores between two groups. CONCLUSION: K-wire placement guided technology is simple and convenient. The application of K-wire placement guided technology could relatively improved disposable K-wire placement rate, shorten the intraoperative fluoroscopy frequencies and reduce complication rates.

miR-107 inhibition upregulates CAB39 and activates AMPK-Nrf2 signaling to protect osteoblasts from dexamethasone-induced oxidative injury and cytotoxicity.

To human osteoblasts dexamethasone (DEX) treatment induces significant oxidative injury and cytotoxicity. Inhibition of CAB39 (calcium binding protein 39)-targeting microRNA can induce CAB39 upregulation, activating AMP-activated protein kinase (AMPK) signaling and offering osteoblast cytoprotection. Here we identified a novel CAB39-targeting miRNA: the microRNA-107 (miR-107). RNA-Pull down assay results demonstrated that the biotinylated-miR-107 directly binds to CAB39 mRNA in OB-6 human osteoblastic cells. Forced overexpression of miR-107, by infection of pre-miR-107 lentivirus or transfection of wild-type miR-107 mimic, largely inhibited CAB39 expression in OB-6 cells and primary human osteoblasts. Contrarily, miR-107 inhibition, by antagomiR-107, increased its expression, resulting in AMPK cascade activation. AntagomiR-107 largely attenuated DEX-induced cell death and apoptosis in OB-6 cells and human osteoblasts. Importantly, osteoblast cytoprotection by antagomiR-107 was abolished with AMPK in-activation by AMPKα1 dominant negative mutation, silencing or knockout. Further studies demonstrated that antagomiR-107 activated AMPK downstream Nrf2 cascade to inhibit DEX-induced oxidative injury. Conversely, Nrf2 knockout almost abolished antagomiR-107-induced osteoblast cytoprotection against DEX. Collectively, miR-107 inhibition induced CAB39 upregulation and activated AMPK-Nrf2 signaling to protect osteoblasts from DEX-induced oxidative injury and cytotoxicity.

microRNA-19a protects osteoblasts from dexamethasone via targeting TSC1.

Activation of mTOR complex 1 (mTORC1) could protect human osteoblasts from dexamethasone. Tuberous sclerosis complex 1 (TSC1) is mTORC1 upstream inhibitory protein. We demonstrate here that microRNA-19a ("miR-19a", -3p) targets the 3' untranslated regions of TSC1 mRNA. Expression of miR-19a downregulated TSC1 in OB-6 osteoblastic cells and primary human osteoblasts. miR-19a activated mTORC1 and protected human osteoblasts from dexamethasone. mTORC1 inhibition, by RAD001 or Raptor shRNA, almost completely abolished miR-19a-induced osteoblast cytoprotection against dexamethasone. Knockdown of TSC1 by targeted shRNA similarly induced mTORC1 activation and protected osteoblasts. Moreover, miR-19a activated mTORC1-dependent NF-E2-related factor 2 (Nrf2) signaling and inhibited dexamethasone-induced reactive oxygen species production in osteoblasts. Together, miR-19a protects human osteoblasts from dexamethasone possibly via targeting TSC1-mTORC1 signaling.

Activation of AMP-activated protein kinase by compound 991 protects osteoblasts from dexamethasone.

Dexamethasone (Dex) induces direct cytotoxicity to cultured osteoblasts. The benzimidazole derivative compound 991 ("C991") is a novel and highly-efficient AMP-activated protein kinase (AMPK) activator. Here, in both MC3T3-E1 osteoblastic cells and primary murine osteoblasts, treatment with C991 activated AMPK signaling, and significantly attenuated Dex-induced apoptotic and non-apoptotic cell death. AMPKα1 knockdown (by shRNA), complete knockout (by CRISPR/Cas9 method) or dominant negative mutation (T172A) not only blocked C991-mediated AMPK activation, but also abolished its pro-survival effect against Dex in osteoblasts. Further studies showed that C991 boosted nicotinamide adenine dinucleotide phosphate (NADPH) activity and induced mRNA expression of NF-E2-related factor 2 (Nrf2)-regulated genes (heme oxygenase-1 and NADPH quinone oxidoreductase 1). Additionally, C991 alleviated Dex-induced reactive oxygen species (ROS) production in osteoblasts. Notably, genetic AMPK inhibition reversed the anti-oxidant actions by C991 in Dex-treated osteoblasts. Together, we conclude that C991 activates AMPK signaling to protect osteoblasts from Dex.

MicroRNA-200a activates Nrf2 signaling to protect osteoblasts from dexamethasone.

Treatment with dexamethasone in human osteoblasts leads to oxidative stress and cell injures. NF-E2-related factor 2 (Nrf2) is a key anti-oxidant signaling. We want to induce Nrf2 activation via microRNA-mediated silencing its suppressor Keap1. Our results show that microRNA-200a ("miR-200a") expression depleted Keap1, causing Nrf2 protein stabilization in OB-6 osteoblastic cells. Reversely, the miR-200a anti-sense led to Keap1 upregulation and Nrf2 degradation. miR-200a expression activated Nrf2 signaling, which inhibited dexamethasone-induced reactive oxygen species production and OB-6 cell death/apoptosis. Keap1 shRNA also activated Nrf2 and protected OB-6 cells from dexamethasone. Importantly, miR-200a was in-effective in Keap1-silenced (by shRNA) OB-6 cells. In the primary human osteoblasts, Keap1 silence by targeted-shRNA or miR-200a protected cells from dexamethasone. Significantly, miR-200a level was decreased in necrotic femoral head tissues, which was correlated with Keap1 mRNA upregulation. Together, miR-200a expression activates Nrf2 signaling and protects human osteoblasts from dexamethasone.

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

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.

Assessment of GSK1904529A as a promising anti-osteosarcoma agent.

The insulin growth factor-I receptor (IGF1R) signaling is a key mechanism for osteosarcoma (OS) cell proliferation. GSK1904529A is a novel small molecule IGF1R kinase inhibitor. Its activity against OS cells was tested. In both established OS cell lines (Saos-2 and MG-63) and primary human OS cells, treatment with GSK1904529A (at nM concentrations) significantly inhibited cell proliferation. At the molecular level, GSK1904529A almost completely blocked IGF1R activation in OS cells, and inhibited downstream AKT-ERK activation. IGF1R silence by targeted shRNA also inhibited AKT-ERK activation and Saos-2 cell proliferation. Significantly, GSK1904529A was unable to further inhibit proliferation of IGF1R-silenced Saos-2 cells. In vivo, GSK1904529A administration orally inhibited Saos-2 tumor growth in nude mice. Together, these results suggest that targeting IGF1R by GSK1904529A inhibits OS cell growth in vitro and in vivo.

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

Excessive glucocorticoid (GC) usage may lead to non-traumatic femoral head osteonecrosis. Dexamethasone (Dex) exerts cytotoxic effect to cultured osteoblasts. Here, we investigated the potential activity of Compound 13 (C13), a novel α1 selective AMP-activated protein kinase (AMPK) activator, against the process. Our data revealed that C13 pretreatment significantly attenuated Dex-induced apoptosis and necrosis in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. AMPK activation mediated C13' cytoprotective effect in osteoblasts. The AMPK inhibitor Compound C, shRNA-mediated knockdown of AMPKα1, or dominant negative mutation of AMPKα1 (T172A) almost abolished C13-induced AMPK activation and its pro-survival effect in osteoblasts. On the other hand, forced AMPK activation by adding AMPK activator A-769662 or exogenous expression a constitutively-active (ca) AMPKα1 (T172D) mimicked C13's actions and inhibited Dex-induced osteoblast cell death. Meanwhile, A-769662 or ca-AMPKα1 almost nullified C13's activity in osteoblast. Further studies showed that C13 activated AMPK-dependent nicotinamide adenine dinucleotide phosphate (NADPH) pathway to inhibit Dex-induced reactive oxygen species (ROS) production in MC3T3-E1 cells and primary murine osteoblasts. Such effects by C13 were almost reversed by Compound C or AMPKα1 depletion/mutation. Together, these results suggest that C13 alleviates Dex-induced osteoblast cell death via activating AMPK signaling pathway.

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.

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

BACKGROUND: Few studies compared radiographic and clinical outcomes between posterior dynamic stabilization (PDS) and posterior lumbar intervertebral fusion (PLIF) in treating degenerative disc disease (DDD). METHODS: A 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. RESULTS: The 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$12826.8 versus US$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. CONCLUSIONS: Compared 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.

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.

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

BACKGROUND: Relatively 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. METHODS: A 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. RESULTS: Among 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 individual's likelihood of surgical complications. CONCLUSIONS: The 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.

[Selection of suitable procedure in the treatment of degenerative lumbar scoliosis based upon imaging studies].

OBJECTIVE: To compare the clinical efficacies of two different procedures in the treatment of degenerative lumbar scoliosis. METHODS: From August 2008 to August 2011, 28 patients of lumbar degenerative scoliosis were divided into one group (n = 14) undergoing modified transforaminal lumbar interbody fusion (TLIF) instrumented surgery and another group (n = 14) undergoing posterolateral fusion (PLF) instrumented surgery. There were 12 males and 16 females with a mean age of 66.2 years (range: 54-79). The operative durations and bleeding volumes of two groups were recorded. The post-operative efficacy was evaluated with VAS (visual analogue scale) for low back pain, ODI (Oswestry disability index), Cobb' angle and lumbar lordosis angle on plain film. RESULTS: The mean follow-up period was 25.9 months. The operative duration was 192.0 ± 44.7 min in modified TLIF group versus 163.0 ± 39.0 min in PLF group. The bleeding volume was 718.0 ± 197.2 ml in modified TLIF group versus 546.0 ± 226.6 ml in PLF group. All operated lumbar intervertebral achieved bony fusion in modified TLIF group by the last follow-up. Two cases had no bony fusion and there was one case of pseudarthrosis in PLF group. Significant differences existed between two groups in pre-operative and post-operative values of VAS, ODI, Cobb' s angle and lumbar lordosis angle (P < 0.05). There were significant differences between two groups in the values of pre-operative and post-operative VAS and lumbar lordosis angle (P < 0.05) but not in the values of pre-operative and post-operative ODI and Cobb' s angle (P > 0.05). CONCLUSION: As an alternative, safe and effective procedure, modified TLIF instrumented is superior to PLF instrumented in the treatment of lumbar degenerative scoliosis.

[Combination of bone marrow concentrate and PGA scaffolds enhancing bone marrow stimulation in the repair of rabbit articular cartilage].

OBJECTIVE: To observe the effects of bone marrow concentrate (BMC)-PGA scaffolds for bone marrow stimulation enhancement and repairing rabbit articular cartilage. METHODS: A rabbit model of articular cartilage defect was established for BMC-PGA stent implantation. After 8 weeks, the experimental animals were sacrificed. And the methods of hematoxylin and eosin stain, toluidine blue stain and immunohistochemistry were used to evaluate the effects of bone marrow stimulation enhancement and rabbit cartilage defect repairing. RESULTS: Visible new cartilage formation was evident after implantation. As compared with other groups, the repairing effect was better. CONCLUSION: The implantation of BMC-PGA scaffolds is both simple and effective in the repair of articular cartilage.

[Treatment of combination atlantoaxial fractures with posterior fusion plus atlantoaxial pedicle screw].

OBJECTIVE: To explore the clinical feasibility, approach, efficacy and indications of posterior fusion plus pedicle screw fixation in the treatment of combination atlantoaxial fractures. METHODS: A retrospective analysis was conducted for 26 cases of Jefferson and dens fracture treated with atlantoaxial pedicle screw from June 2008 to May 2010. RESULTS: The postoperative radiographs verified an excellent position of all screws with a satisfactory atlantoaxial reduction. Operative time was (126 ± 26) min, and blood loss was (350 ± 107) ml. During an average follow-up period of 14 months (range: 6 - 28), it showed no spine cord and vertebral artery injury or interfixation failure. Atlantoaxial alignment and stability were restored without any instrumentation-related complication. CONCLUSION: Posterior atlantoaxial pedicle screw and rod fixation may provide immediate three-dimensional rigid fixation of atlantoaxial joint. This technique is more effective than other previously reported approaches.

[Treatment of degenerative lumbar scoliosis via posterior decompression and fusion with internal fixation].

OBJECTIVE: To explore the pathogenic mechanism, operative techniques and therapeutic efficacy of lumbar degenerative scoliosis. METHODS: A retrospective analysis was performed for 32 patients (14 males and 18 females with a mean age of 67.4 years old) with degenerative lumbar scoliosis undergoing posterior decompression and fusion with pedicle screw system from January 2007 to March 2010. The post-operative outcomes were radiologically evaluated with Oswestry disability index (ODI), Cobb' angle and lumbar lordosis angle. RESULTS: All patients received a mean follow-up of 28.5 months (range: 12 - 50). All lumbar joints achieved bony fusion at Month 6 post-operation. No complications occurred due to instrumentation. There was no pseudoarthrosis. The significant differences of ODI existed between pre-operation and post-operation [(60 ± 11)% vs (21 ± 6)%, P < 0.01], Cobb' angle [(28 ± 9)° vs (13 ± 5)°, P < 0.01] and lumbar lordosis angle [(41 ± 12)° vs (20 ± 10)°, P < 0.01]. CONCLUSION: Individualized operations should be performed for degenerative lumbar scoliosis patients. Proper lumbar decompression and the reconstruction of coronal and sagittal balances may relieve symptoms and improve the quality of life.

[Pedicle screw implanting in the treatment of multi-level lumbar spine fractures].

OBJECTIVE: To review the clinical data of a group of patients with multi-level lumbar spine fractures treated with TSRH-3D pedicle screw system and to investigate the effect and post-operative efficacy of this technique. METHODS: Eighteen patients diagnosed as multi-level lumbar spine fracture were treated with TSRH-3D pedicle screw system. The operations were performed at 4 hours to 2 days after injury and the follow-up period was 15-32 months (mean: 23 months). The X-ray and CT scan were taken both preoperatively and postoperatively. RESULTS: (1) Twelve patients became injured from height falling (67%), 5 from traffic accident (28%) and 1 from crush (5%). (2) The improvement rate of spine motion, back pain and lower extremity pain was 67%, 94% and 78% respectively. (3) Compared with preoperative status, the height of anterior border of vertebra improved by 59.2%, lost by an average of 5.2% (P < 0.01) and the Cobb angle was corrected by 19.5 degrees , lost an average of 5.4 degrees . CONCLUSION: It is feasible to treat the multi-level lumbar spine fractures with TSRH-3D pedicle screw system. And the outcome of reduction and fixation is satisfactory. This technique is excellent at improving the height of injury vertebra, physiological curvature and neural function. It also can relieve lumbocrural pain with a definite postoperative efficacy.