Pricing strategies for new product and remanufactured product considering emission sensitive demand.

With the rapidly increasing concern on environmental pollution and resource shortage, remanufactured products attract many attentions. In order to determine the optimal production and pricing strategy, we construct decision models for both single-product market and mixed-product market. Consumers' different preferences for new products and remanufactured products are considered. First, we construct pricing models for a single-product market, and achieve a judging condition to determine the optimal strategy. Second, we develop a pricing model for a multiple-product market and put forward a suppose to show that the multiple-product strategy is not always optimal. Finally, numerical illustrations are designed to examine the impacts of the two crucial factors and obtain the dominant regions for each strategy. By introducing an emission sensitive demand, we show the superiority of the remanufactured product when the extra demand attracted by the emission saving is large.

Polyphyllin I suppressed the apoptosis of intervertebral disc nucleus pulposus cells induced by IL-1ß by miR-503-5p/Bcl-2 axis.

BACKGROUND: There are no studies that have shown the role and underlying mechanism of Polyphyllin I (PPI)-mediated anti-apoptosis activity in nucleus pulposus cells (NPCs). The research aimed to evaluate the effects of PPI in interleukin (IL)-1ß-induced NPCs apoptosis in vitro. METHODS: Cell Counting Kit-8 (CCK-8) assay was used to detect cell viability, and cell apoptosis was evaluated by double-stained flow cytometry (FITC Annexin V/PI). The expression of miR-503-5p was quantified by real-time quantitative PCR (qRT-PCR), and the expression of Bcl-2, Bax, and cleaved caspase-3 was quantified by Western blot. Dual-luciferase reporter gene assay was used to detect the targeting relationship between miR-503-5p and Bcl-2. RESULTS: PPI at 40 µg·mL-1 markedly promoted the viability of NPCs (P < 0.01). Also, PPI inhibited apoptosis and reduction in proliferative activity induced by IL-1ß in the NPCs (P < 0.001, 0.01). PPI treatment significantly inhibited the expression of apoptosis-related protein Bax, cleaved caspase-3 (P < 0.05, 0.01), and enhanced the level of anti-apoptotic protein Bcl-2 (P < 0.01). The proliferative activity of NPCs was significantly decreased and the apoptosis rate of NPCs was increased under IL-1ß treatment (P < 0.01, 0.001). Moreover, miR-503-5p was highly expressed in IL-1ß-induced NPCs (P < 0.001). Furthermore, the effect of PPI on NPCs viability and apoptosis in IL-1ß treatment was dramatically reversed by the overexpression of miR-503-5p (P < 0.01, 0.01). The targeted binding of miR-503-5p to the 3'UTR of Bcl-2 mRNA was confirmed by dual-luciferase reporter gene assays (P < 0.05). In further experiments, compared with miR-503-5p mimics, the effects of PPI on IL-1ß-induced NPCs viability and apoptosis were greatly reversed by the co-overexpression of miR-503-5p and Bcl-2 (P < 0.05, 0.05). CONCLUSION: PPI suppressed the apoptosis of intervertebral disk (IVD) NPCs induced by IL-1ß via miR-503-5p/Bcl-2 molecular axis.

Risk Factors of Postoperative Cerebrospinal Fluid Leak After Craniovertebral Junction Anomalies Surgery: A Case-Control Study.

OBJECTIVE: To identify potential risk factors for cerebrospinal fluid (CSF) leakage after craniovertebral junction (CVJ) anomaly surgery and to provide a reference for clinical practice. METHODS: Sixty-six patients who underwent elective CVJ anomaly surgery during a 6-year period (April 2013 to September 2019) were retrospectively included. Research data were collected from the patients' medical records and imaging systems. Patients were divided into CSF leak and no CSF leak groups. Univariate tests were performed to identify potential risk factors. For statistically significant variables in the univariate tests, a logistic regression test was used to identify independent risk factors for CSF leakage. RESULTS: The overall prevalence of CSF leakage was 13.64%. Univariate tests showed that a basion-dental interval (BDI) > 10 mm and occipitalized atlas had significant intergroup differences (p < 0.05). Multivariate analysis indicated that a BDI > 10 mm was an independent risk factor for CSF leakage, and patients with CVJ anomalies with a BDI > 10 mm were more likely to have postoperative CSF leaks (odds ratio, 14.67; 95% confidence interval, 1.48-30.88; p = 0.004). CONCLUSION: It is necessary to maintain vigilance during CVJ anomaly surgery in patients with a preoperative BDI > 10 mm to avoid postoperative CSF leaks.

Accumulation of NCOA1 dependent on HERC3 deficiency transactivates matrix metallopeptidases and promotes extracellular matrix degradation in intervertebral disc degeneration.

BACKGROUND: Matrix metallopeptidases (MMPs) are critical matrix-degrading molecules and they are frequently overexpressed in degenerative discs. This study aimed to investigate the mechanism for MMP upregulation. METHODS: Immunoblot and RT-qPCR were used for detecting protein and gene expression levels. 4-month-old and 24-month-old C57BL/6 mice were used for evaluating intervertebral disc degeneration (IDD). An ubiquitination assay was used to determine protein modification. Immunoprecipitation and mass spectrometry were used for identifying protein complex members. RESULTS: We identified the elevation of 14 MMPs among 23 members in aged mice with IDD. Eleven of these 14 MMP gene promoters contained a Runx2 (runt-related transcription factor 2) binding site. Biochemical analyses revealed that Runx2 recruited a histone acetyltransferase p300 and a coactivator NCOA1 (nuclear receptor coactivator 1) to assemble a complex, transactivating MMP expression. The deficiency of an E3 ligase called HERC3 (HECT and RLD domain containing E3 ubiquitin-protein ligase 3) resulted in the accumulation of NCOA1 in the inflammatory microenvironment. High throughput screening of small molecules that specifically target the NCOA1-p300 interaction identified a compound SMTNP-191, which showed an inhibitory effect on suppressing MMP expression and attenuating the IDD process in aged mice. CONCLUSION: Our data support a model in which deficiency of HERC3 fails to ubiquitinate NCOA1, leading to the assembly of NCOA1-p300-Runx2 and causing the transactivation of MMPs. These findings offer new insight into inflammation-mediated MMP accumulation and also provide a new therapeutic strategy to retard the IDD process.

Retracted Article: Exosomes from bone marrow mesenchymal stem cells promoted osteogenic differentiation by delivering miR-196a that targeted Dickkopf-1 to activate Wnt/ß-catenin pathway.

Statement of RetractionWe, the Publisher of the journal Bioengineered, have retracted the following article:Zhi Peng et al - Exosomes from bone marrow mesenchymal stem cells promoted osteogenic differentiation by delivering miR-196a that targeted Dickkopf-1 to activate Wnt/ß-catenin pathway, Bioengineered (2021) (DOI: https://www.10.1080/21655979.2021.1996015)Since publication, significant concerns have been raised about the integrity of the data and reported results in the article. When approached for an explanation, the authors checked their data and confirmed there are fundamental errors present. Therefore, they have agreed to the retraction of this article. The authors apologise for this oversight.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as 'Retracted'.

Hsa_circ_0001020 accelerates the lower extremity deep vein thrombosis via sponging miR-29c-3p to promote MDM2 expression.

BACKGROUND: Deep vein thrombosis (DVT) is a serious venous thromboembolism and leads the morbidity and mortality worldwide. Circular RNAs (circRNAs) sever as the important function biomarkers in various diseases, including DVT. However, the regulatory mechanism of circRNAs in DVT remains unclear. Here, we aimed to explore the function and potential mechanism of circRNAs in lower extremity deep vein thrombosis formation in DVT. METHODS: QRT-PCR and western blot were performed to detect the expression of hsa_circ_0001020, miR-29c-3p, and MDM2 expression in human peripheral blood of DVT and endothelial progenitor cells (EPCs), respectively. Flow cytometry, RNA FISH and immunofluorescence detected the expression of distribution of circ_0001020 and CD31+ and CD34+ cells. RIP, RNA-pull down, and dual-luciferase reporter gene system were used to determine the binding relationship between hsa_circ_0001020, miR-29c-3p, and MDM2. Wound healing, transwell, and tube formation assays detected cell migration, invasion, and angiogenesis in vitro. DVT mice model was constructed to validate the function of hsa_circ_0001020, and H&E and Carstairs staining were performed to evaluate the pathology of inferior vena cava (IVC). RESULTS: Hsa_circ_0001020 and MDM2 upregulated, whereas miR-29c-3p downregulated in DVT patients and mouse model. Hsa_circ_0001020 sponged miR-29c-3p to promote MDM2 expression thus inhibited EPC migration, invasion and tube formation. And the function of hsa_circ_0001020 and regulatory mechanism was demonstrated by the lose-function of hsa_circ_0001020 and rescue experiment. In DVT mice, hsa_circ_0001020 knockdown suppressed thrombosis and promoted homing ability of EPCs into thrombi. CONCLUSION: Our finding demonstrated a novel signaling pathway involving hsa_circ_0001020, miR-29c-3p, MDM2, which might be a potential therapeutic target for DVT.

Microarray profile of circular RNAs identifies hsa_circ_000455 as a new circular RNA biomarker for deep vein thrombosis.

OBJECTS: Deep vein thrombosis is a type of severe venous thromboembolism that can result in high mortality and morbidity. The expression alternation of circular RNAs (circRNAs) has been found in various diseases. However, the function of circRNAs in deep vein thrombosis still remains unknown. METHOD: The blood samples of deep vein thrombosis patients and health control were selected, circRNA microarray was performed, and qPCR was used to verify the expression of circRNAs. Also, GO/KEGG analysis was performed, and hsa_circ_RNA_000455-targeted miRNA-mRNA network was predicted. RESULT: Here, we found that 303 circRNAs were differentially expressed in deep vein thrombosis using microarray, of which 83 circRNAs were upregulated and 220 circRNAs were downregulated. The expression of five circRNAs verified by quantitative real-time PCR was consistent with the result of microarray. GO analysis showed that the top 100 differentially expressed circRNAs in deep vein thrombosis patients were closely related to protein transport, cytoplasm, and Adenosine Triphosphate (ATP) binding. The most significantly enriched pathways by KEGG analysis included thyroid hormone-signaling pathway, endocytosis, proteoglycans in cancer, Fc gamma R-mediated phagocytosis, focal adhesion, insulin-signaling pathway, p53-signaling pathway, biosynthesis of antibiotics, bacterial invasion of epithelial cells, and AMP-activated protein kinase-signaling pathway. Then, hsa_circ_000455 was selected, and the function of hsa_circ_000455 in the pathogenesis of deep vein thrombosis was analyzed via circRNA-miRNA-mRNA network. We therefore hypothesized that hsa_circRNA_000455/hsa-miR-22-3p/NLRP3 may involve in the development of deep vein thrombosis. CONCLUSION: This study provided valuable information on circRNA profile in deep vein thrombosis for the first time and gave clues on the possible role and mechanism of hsa_circRNA_000455 in deep vein thrombosis.

Characterization and in vitro assessment of three-dimensional extrusion Mg-Sr codoped SiO2-complexed porous microhydroxyapatite whisker scaffolds for biomedical engineering.

BACKGROUND: Large bone defects have always been a great challenge for orthopedic surgeons. The use of a good bone substitute obtained by bone tissue engineering (BTE) may be an effective treatment method. Artificial hydroxyapatite, a commonly used bone defect filler, is the main inorganic component of bones. Because of its high brittleness, fragility, and lack of osteogenic active elements, its application is limited. Therefore, its fragility should be reduced, its osteogenic activity should be improved, and a more suitable scaffold should be constructed. METHODS: In this study, a microhydroxyapatite whisker (mHAw) was developed, which was doped with the essential trace active elements Mg2+ and Sr2+ through a low-temperature sintering technique. After being formulated into a slurry, a bionic porous scaffold was manufactured by extrusion molding and freeze drying, and then SiO2 was used to improve the mechanical properties of the scaffold. The hydrophilicity, pore size, surface morphology, surface roughness, mechanical properties, and release rate of the osteogenic elements of the prepared scaffold were detected and analyzed. In in vitro experiments, Sprague-Dawley (SD) rat bone marrow mesenchymal stem cells (rBMSCs) were cultured on the scaffold to evaluate cytotoxicity, cell proliferation, spreading, and osteogenic differentiation. RESULTS: Four types of scaffolds were obtained: mHAw-SiO2 (SHA), Mg-doped mHAw-SiO2 (SMHA), Sr-doped mHAw-SiO2 (SSHA), and Mg-Sr codoped mHAw-SiO2 (SMSHA). SHA was the most hydrophilic (WCA 5°), while SMHA was the least (WCA 8°); SMHA had the smallest pore size (247.40 ± 23.66 µm), while SSHA had the largest (286.20 ± 19.04 µm); SHA had the smallest Young's modulus (122.43 ± 28.79 MPa), while SSHA had the largest (188.44 ± 47.89 MPa); and SHA had the smallest compressive strength (1.72 ± 0.29 MPa), while SMHA had the largest (2.47 ± 0.25 MPa). The osteogenic active elements Si, Mg, and Sr were evenly distributed and could be sustainably released from the scaffolds. None of the scaffolds had cytotoxicity. SMSHA had the highest supporting cell proliferation and spreading rate, and its ability to promote osteogenic differentiation of rBMSCs was also the strongest. CONCLUSIONS: These composite porous scaffolds not only have acceptable physical and chemical properties suitable for BTE but also have higher osteogenic bioactivity and can possibly serve as potential bone repair materials.

LncRNA Sirt1-AS upregulates Sirt1 to attenuate aging related deep venous thrombosis.

Aging is associated with the increased incidence of deep venous thrombosis (DVT), resulting in significant morbidity and mortality in the elderly, but the underlying mechanism is elusive. Silent information regulator 1 (Sirt1) is linked to the senescence, inflammation, oxidative stress and platelet adhesion of endothelial cells. Here we showed that DVT was associated with the senescence of endothelium and lower expression of Sirt1. Furthermore, Sirt1 could inhibit endothelial senescence and reduce the occurrence of DVT. Interestingly, we found antisense long non-coding RNA (lncRNA Sirt1-AS) upregulated Sirt1, decreased the expression of senescence and DVT associated biomarkers in human vascular endothelial cells (HUVECs). In addition, lncRNA Sirt1-AS overexpression alleviated DVT through upregulating Sirt1 and thereby inducing Foxo3a degradation. In conclusion, our findings demonstrate that lncRNA Sirt1-AS may be a potential new biomarker for DVT.

LncRNA MALAT1 exhibits positive effects on nucleus pulposus cell biology in vivo and in vitro by sponging miR-503.

BACKGROUND: Intervertebral disc degeneration (IDD) is characterized by the loss of nucleus pulposus cells (NPCs) and phenotypic abnormalities. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) are involved in the pathogenesis of IDD. In this study, we aimed to investigate the functional effects of lncRNA MALAT1 on NPCs in IDD and the possible mechanism governing these effects. RESULTS: We validated the decreased expression of MALAT1 in the IDD tissues, which was associated with decreased Collagen II and Aggrecan expression. In vitro, overexpressed MALAT1 could attenuate the effect of IL-1ß on NPC proliferation, apoptosis, and Aggrecan degradation. In vivo, MALAT1 overexpression attenuated the severity of disc degeneration in IDD model rats. Our molecular study further demonstrated that MALAT1 could sponge miR-503, modulate the expression of miR-503, and activate downstream MAPK signaling pathways. The effects of MALAT1 on NPCs were partially reversed/aggregated by miR-503 mimics/inhibitor treatment. CONCLUSION: Our data suggested that the MALAT1-miR-503-MAPK pathway plays a critical role in NPCs, which may be a potential strategy for alleviating IDD.

The CtBP1-HDAC1/2-IRF1 transcriptional complex represses the expression of the long noncoding RNA GAS5 in human osteosarcoma cells.

Growth Arrest Specific 5 (GAS5), a long noncoding RNA (lncRNA), functions as a tumor suppressor in multiple cancers. However, its function, downstream targets and upstream regulatory mechanism are still obscure in osteosarcoma cells. Here, we discovered that GAS5 was downregulated in cancerous osteosarcoma tissues and cells. Using a microarray analysis, we identified that GAS5 can regulate the expression of TP53, Bax, Bim, DDB2, TGFB and ROS1 in osteosarcoma cells. Specifically, GAS5 overexpression in the U2OS osteosarcoma cell line induced TP53, Bax and Bim levels but inhibited DDB2, TGFB and ROS1 expression, resulting in the inhibition of cell proliferation, invasion, colony formation and in vivo tumor formation. By analyzing the GAS5 promoter region (-2000), we identified several potential transcription factor-binding sites including NF-ĸB, IK-1, AP-1, SP1 and IRF1. By individually knocking down these transcription factors, we found that only knockdown of IRF1 affected GAS5 expression. Using immunoprecipitation (IP), mass spectrometry assays, and co-IP assays, we identified that IRF1 formed a transcriptional complex with Histone Deacetylase 1 and 2 (HDAC1/2) and C-terminal binding protein 1 (CtBP1). Functional analyses indicated that the CtBP1-HDAC1/2-IRF1 complex specifically bound to the GAS5 promoter and regulated its expression and downstream events. Knockdown of CtBP1 or overexpression of IRF1 in osteosarcoma cells can significantly reverse their oncogenic phenotypes. Altogether, our results indicated that the CtBP1-HDAC1/2-IRF1 transcriptional complex inhibited GAS5-mediated signaling in osteosarcoma cells, and it might be a potential therapeutic target for osteosarcoma treatment.

Upregulation of the long noncoding RNA lncPolE contributes to intervertebral disc degeneration by negatively regulating DNA polymerase epsilon.

Long noncoding RNAs (lncRNAs) are critical regulators of gene transcription. Our previous results have demonstrated that iron deficiency accelerates intervertebral disc degeneration (IDD) by affecting the stability of the DNA polymerase epsilon (Polε) complex. Here, we discovered that the novel lncRNA lncPolE functions as a negative regulator of Polε. The expression of lncPolE in IDD tissues was upregulated compared to its expression in healthy control tissues, and this was in contrast to the PolE1 expression levels. The increased lncPolE level was significantly correlated with the severity of IDD. Ectopic expression of lncPolE in human nucleus pulposus cells (hNPCs) was able to decrease PolE1 levels and cause apoptosis, while the specific knockdown of lncPolE in primary NP cells (pNPCs) from IDD patients can restore PolE1 levels. Interestingly, iron depletion or supplementation can affect the expression of lncPolE. Further analyses indicated that the downregulation of DNA methylation in the promoter region of lncPolE caused its overexpression. Collectively, our results suggest that the aberrant expression of lncPolE contributes to the pathogenesis of IDD by negatively regulating PolE1 in iron deficient conditions, and this may provide a new avenue to alleviate IDD progression in clinical treatment.

miR-142-5p promotes the osteoclast differentiation of bone marrow-derived macrophages via PTEN/PI3K/AKT/FoxO1 pathway.

It is increasingly recognized that microRNAs (miRNAs) are a kind of important regulators, which are involved in the pathogenesis and development of various human diseases. However, the underlying effects and mechanism of miR-142-5p on the osteoclast differentiation of bone marrow-derived macrophages (BMMs) have not been elucidated. The aim of the present study is to explore the molecular mechanisms that regulate the osteoclastogenesis of BMMs for providing more efficient methods for treating bone-related diseases. In the present study, BMMs were isolated from rats and cultured. Moreover, receptor activators of NF-kB ligands were used to induce the osteoclast differentiation of BMMs. Furthermore, we analyzed the effects of miR-142-5p mimics/inhibitor on the osteoclastogenesis of BMMs. The results indicated that the downregulation of miR-142-5p inhibited the osteoclastogenesis of BMMs, whereas the overexpression enhanced this process. PTEN was testified to be a direct target of miR-142-5p, and its effects on the osteoclastogenesis were also described. Most importantly, treatment of LY29004 (an inhibitor of the PI3k/Akt pathway) can attenuate miR-142-5p osteoclastogenesis effects, while the inhibition effects of LY29004 on the osteoclastogenesis were abolished by knockdown of FoxO1. Taken together, our findings demonstrated that miR-142-5p promotes the osteoclastogenesis of BMMs through PI3k/Akt/FoxO1 pathway via targeting PTEN.

MicroRNA485-3p negatively regulates the transcriptional co-repressor CtBP1 to control the oncogenic process in osteosarcoma cells.

Carboxyl-terminal binding protein 1 (CtBP1), a well-known transcriptional co-repressor, is highly expressed in a number of cancer types. However, it is still absent in osteosarcoma cells. Here, we found that CtBP1, but not CtBP2, is overexpressed in invasive osteosarcoma tissues and cells. The overexpressed CtBP1 in turn represses its downstream targets, such as the pro-apoptotic regulators Bax, Bim and p53 upregulated modulator of apoptosis (PUMA), cell adhesion molecule E-cadherin, and the cell cycle regulators p16, p21 and phosphatase and tensin homolog (PTEN). To explore the molecular mechanism of CtBP1 overexpression, we subjected three independent clinical samples to miRNA microarray analysis and found that miR-485-3p could specifically bind to the 3'-untranslated region (3'-UTR) of CtBP1, thereby negatively controlling CtBP1 expression. The overexpression of miR-485-3p in osteosarcoma cells significantly repressed CtBP1 levels and inhibited cell proliferation, colony formation, cell migration and sphere formation. Further analysis indicated that DNA hypermethylation in the promoter region of miR-485-3p caused the downregulation of miR-485-3p. Treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine (AZA) resulted in the upregulation of miR-485-3p and the downregulation of CtBP1 as well as inhibited osteosarcoma cell growth. This study provides evidence that CtBP1 is also overexpressed in osteosarcoma cells and demonstrates the underlying mechanism regarding its overexpression. Thus, therapeutically targeting CtBP1 may represent an effective strategy for osteosarcoma therapy.

Resveratrol attenuates hydrogen peroxide­induced apoptosis, reactive oxygen species generation, and PSGL­1 and VWF activation in human umbilical vein endothelial cells, potentially via MAPK signalling pathways.

Reactive oxygen species (ROS) are implicated in the pathogenesis of thrombosis. Studies have reported that resveratrol exhibits antioxidative activities, however, the effect and underlying mechanisms of resveratrol on venous thrombosis remain largely unknown. To investigate the effect of resveratrol on venous thrombosis and the underlying mechanisms, the present study investigated the effects of resveratrol on cell viability, apoptosis, ROS generation and the expression of thrombosis­associated markers in human umbilical vein endothelial cells (HUVECs). HUVECs were pretreated with resveratrol for 2 h and incubated with hydrogen peroxide (H2O2) for 24 h prior to the evaluation of cell viability, ROS generation, apoptosis and thrombosis­associated marker expression by performing MTT assays, 2',7'­dichlorofluorescin diacetate reagent, flow cytometry, and reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and western blot analysis, respectively. Subsequently, to validate whether resve-ratrol functions via mitogen­activated protein kinase (MAPK) pathways, the expression of thrombosis­associated markers was detected by western blot analysis and RT­qPCR following treatment of cells with resveratrol and the MAPK pathway activators anisomycin and curcumin. The results demonstrated that cell viability was markedly reduced by H2O2, and resveratrol treatment reversed the reductions in cell viability in a dose­dependent manner. In addition, the levels of cell apoptosis and ROS generation were significantly increased by H2O2 alone, and resveratrol also reduced these effects in a dose­dependent manner. Furthermore, the mRNA and protein expression of caspase­3, P­selectin glycoprotein ligand­1 and von Willebrand factor was upregulated by H2O2 treatment in HUVECs. However, resveratrol decreased the protein expression these proteins in a dose­dependent manner. Resveratrol also significantly inhibited the induction of phosphorylated (p)­p38, P­c­Jun N­terminal kinase and P­extracellular signal­regulated kinase by H2O2, and these effects were attenuated by the MAPK pathway activators anisomycin and curcumin. In conclusion, these results indicate that resveratrol protected HUVECs against oxidative stress and apoptosis. Furthermore, to the best of our knowledge, the present study is the first to demonstrate that resveratrol attenuates the expression of thrombosis­associated markers induced by H2O2, which may occur through the suppression of the MAPK signalling pathways, indicating a potential novel therapeutic approach to prevent venous thrombosis.

Transpedicular Excision of a Thoracic Intraspinal Osteochondroma in a Patient with Hereditary Multiple Exostoses and Brown-Séquard Syndrome.

BACKGROUND: Spinal osteochondroma is a rare but recognized cause of myelopathy. Brown-Séquard syndrome is a form of severe myelopathy characterized by a clinical picture of hemisection of the spinal cord. Brown-Séquard syndrome caused by osteochondroma is extremely rare, calling for individualized surgical procedures. CASE DESCRIPTION: We report a 16-year-old girl with hereditary multiple exostoses and a rare case of thoracic osteochondroma causing partial Brown-Séquard syndrome. Customized surgical procedures were designed to avoid iatrogenic spinal cord injury. The patient underwent neural decompression and tumor excision through a transpedicular approach. The surgical procedure consisted of 4 consecutive steps: 1) laminectomy, 2) costotransversectomy and pediculectomy, 3) extracavitary removal of the mass, and 4) pedicular fixation with fusion. Total resection of the tumor was achieved macroscopically without intraoperative spinal cord injury. The postoperative recovery was uneventful, and the patient returned to a normal life without evidence of recurrence at 24-month follow-up. CONCLUSIONS: For patients with hereditary multiple exostosis and new onset of neurologic symptoms, the possibility of a spinal osteochondroma should be considered. In the situation of an intraspinal exostosis protruding from the lateral side, customized surgical procedures with a transpedicular approach may be a valid way to minimize intraoperative neural injury and achieve a satisfactory outcome.

Iron deficiency accelerates intervertebral disc degeneration through affecting the stability of DNA polymerase epsilon complex.

Iron serves as an important cofactor of iron-containing proteins that play critical roles in the maintenance of DNA stability and cell cycle progression. The disturbed iron homeostasis results in the pathogenesis of many diseases such as cancer and anemia. In this study, we found a clear correlation between iron deficiency and intervertebral disc degeneration (IDD). Through microarray experiments, we found that a large number of genes were differentially expressed in tissues with different degrees of degeneration. Among them, an iron-containing gene, PolE, the catalytic subunit of DNA polymerase epsilon (Polε), and the other two Polε subunits, including PolE2 and PolE3, were markedly downregulated, while some proteins involved in apoptosis such as Caspase-3 and -8 were significantly upregulated. By supplementation with an iron chelator deferoxamine (DFO) or knocking down either iron divalentmetal transporter 1 (DMT1) or transferrin receptor 1 (TfR1) in the nucleus pulposus (NP) cells, we found that the protein levels of PolE complex members were dramatically reduced, whereas the intrinsic apoptotic pathway was activated. Interestingly, overexpression of PolE in NP cells knocked down with either DMT1 or TfR could not reverse the stability of PolE complex and apoptosis status. In summary, our study suggests that iron deficiency is an important factor in the aggravation of IDD. Proper iron supplementation may be an effective strategy to alleviate the symptoms of patients with IDD.