The association between ambient air pollution exposure and connective tissue sarcoma risk: a nested case-control study using a nationwide population-based database.

A nationwide population-based database was utilized in a nested case-control study to explore the association between ambient air pollution exposure and the likelihood of developing connective tissue sarcoma. The study examined 280 cases of connective tissue sarcoma diagnosed between 2000 and 2012. A random sample of 1120 control subjects was selected from a subpopulation of claim records without a connective tissue sarcoma diagnosis in a 1:4 ratio. The control subjects were selected based on similar characteristics as the connective tissue sarcoma patients, including gender, birth year, and the year of diagnosis of the case group with medical records. Risk factors for connective tissue sarcoma were collected for analysis. Our data on exposure to air pollutants was collected from Taiwan's Air Quality Monitoring Network, which has been gathering air quality data from a growing network of sampling stations (now 76) throughout the country since 1997. It was discovered that the risk of connective tissue sarcoma was significantly increased by the Charlson comorbidity index (CCI), elevated levels of specific air pollution indices (e.g., total hydrocarbons (THC), fine particulate matter (PM2.5), and O3_8 (the annual mean of the daily maximum 8-h average concentration of O3), the High Pollutant Standards Index (hPSI) (the percentage of days in a given year in Taiwan where the PSI exceeds 100), and an insurable monthly wage over US$1100. Further investigation is needed to explore the involvement of these air pollutants in the formation of connective tissue sarcoma.

Anti-tumor effects of deubiquitinating enzyme inhibitor PR-619 in human chondrosarcoma through reduced cell proliferation and endoplasmic reticulum stress-related apoptosis.

Chondrosarcoma, a treatment-resistant cancer with limited therapeutic options, lacks significant advancements in treatment methods. However, PR-619, a novel inhibitor of deubiquitinating enzymes, has demonstrated anti-tumor effects in various malignancies. This study aimed to investigate the impact of PR-619 on chondrosarcoma both in vitro and in vivo. Two human chondrosarcoma cell lines, SW11353 and JJ012, were utilized. Cell viability was assessed using an MTT assay, while flow cytometry enabled the detection of apoptosis and cell cycle progression. Western blotting analyses were conducted to evaluate apoptosis, cell stress, and endoplasmic reticulum (ER) stress. Furthermore, the in vivo anti-tumor effects of PR-619 were examined using a xenograft mouse model. The results revealed that PR-619 induced cytotoxicity, apoptosis, and cell cycle arrest at the G0/G1 stage by activating caspases, PARP cleavage, and p21. Moreover, PR-619 increased the accumulation of polyubiquitinated proteins and ER stress by activating IRE1, GRP78, caspase-4, CHOP, and other cellular stress responses, including JNK activation. In vivo analysis demonstrated that PR-619 effectively inhibited tumor growth with minimal toxicity in the xenograft mouse model. These findings provide evidence of the anti-tumor effects and induction of cellular and ER stress by PR-619 in human chondrosarcoma, suggesting its potential as a novel therapeutic strategy for in human chondrosarcoma.

Manipulation of osteogenic and adipogenic differentiation of human degenerative disc and ligamentum flavum derived progenitor cells using IL-1ß, IL-19, and IL-20.

PURPOSE: To elucidate whether pro-inflammatory cytokines might influence the commitment of intervertebral disc (IVD)- and ligamentum flavum (LF)-derived progenitor cells toward either osteogenesis or adipogenesis, specifically Interleukin-1ß (IL-1ß), IL-19, and IL-20. METHODS: Sixty patients with degenerative spondylolisthesis and lumbar or lumbosacral spinal stenosis were included in the study. Injuries to the spine, infections, and benign or malignant tumors were excluded. From nine patient samples, IVD- and LF-derived cells were isolated after primary culture, and two clinical samples were excluded due to mycoplasma infection. The effects of IL-1ß, IL-19, as well as IL-20 in regulating osteogenic and adipogenic differentiation in vitro were investigated. RESULTS: Primary IVD- and LF-derived cells were found to have a similar cell morphology and profile of surface markers (CD44, CD90, and CD105) as placenta-derived mesenchymal stem cells (MSCs). Primary IVD/LF cells have a high capacity to differentiate into osteocytes and adipocytes. IL-19 had a tendency to promote adipogenesis. IL-20 inhibited osteogenesis and promoted adipogenesis; IL-1ß promoted osteogenesis but inhibited adipogenesis. CONCLUSION: IL-1ß, IL-19, and IL-20 impact the adipogenic and osteogenic differentiation of IVD-derived and LF-derived cells. Modulating the expression of IL-1ß, IL-19, and IL-20 provides a potential avenue for controlling cell differentiation of IVD- and LF-derived cells, which might have beneficial effect for degenerative spondylolisthesis and spinal stenosis.

A methodology to evaluate different histological preparations of soft tissues: Intervertebral disc tissues study.

A tissue preparation method will inevitably alter the tissue content. This study aims to evaluate how different common sample preparation methods will affect the tissue morphology, biomechanical properties, and chemical composition of samples. The study focuses on intervertebral disc (IVD) tissue; however, it can be applied to other soft tissues. Raman spectroscopy synchronized with nanoindentation instrumentation was employed to investigate the compositional changes of IVD, specifically, nucleus pulposus (NP) and annulus fibrosus (AF), together with their biomechanical properties of IVD. These properties were examined through the following histological specimen types: fresh cryosection (control), fixed cryosection, and paraffin-embedded. The IVD tissue could be located using an optical microscope under three different preparation methods. Paraffin-embedded samples showed the most explicit details where the lamellae structure of AF could be identified. In terms of biomechanical properties, there was no significant difference between the fresh and fixed cryosection (p > 0.05). In contrast, the fresh cryosection and paraffin-embedded samples showed a significant difference (p < 0.05). It was also found that the tissue preparations affected the chemical content of the tissues and structure of the tissue, which are expected to contribute to biomechanical properties changes. Fresh cryosection and fixed cryosection samples are more promising to work with for biomechanical assessment in histological tissues. The findings fill essential gaps in the literature by providing valuable insight into the characteristics of IVD at the microscale. This study can also become a reference for a better approach to assessing the mechanical properties and chemical content of soft tissues at the microscale.

Correlation of the degenerative stage of a disc with magnetic resonance imaging, chemical content, and biomechanical properties of the nucleus pulposus.

Intervertebral disc degeneration (IDD) is closely related to changes in the intervertebral disc (IVD) composition and the resulting viscoelastic properties. IDD is a severe condition because it decreases the disc's ability to resist mechanical loads. Our research aims to understand IDD at the cellular level, specifically the changes in the viscoelastic properties of the nucleus pulposus (NP), which are poorly understood. This study employed a system integrating nanoindentation with Raman spectrometry to correlate biomechanics with subtle changes in the biochemical makeup of the NP. The characterization was, in turn, correlated with the degenerative severity of IVD as assessed using magnetic resonance imaging (MRI) of different patients with spinal stenosis, degenerative spondylolisthesis, and degenerative scoliosis. It is shown that there is an increase in the crosslinking ratio in collagen, a reduction in proteoglycan, and a build-up of minerals upon the rise in the severity level of the disc damage in the NP. Assessment of mechanical characteristics reveals that the increasing disc degeneration makes the NP lose its elasticity, becoming more viscous. This shows that the tissue undergoes abnormalities in weight-bearing ability, which contributes to spinal instability. The correlation of the individual discs shows that grades III and IV have similarities in the changes of Amide I and III toward the storage modulus. In contrast, grades IV and V correlate with mineralization toward the storage modulus. Reduction of proteoglycan has the highest impact on the changes of the storage modulus in all grades of IDD. Connecting compositional alterations to IVD micromechanics at various degrees of degeneration expands our understanding of tissue behavior and provides critical insight into clinical diagnostics, treatment, and tissue engineering.

Optimization of Spinal Reconstructions for Thoracolumbar Burst Fractures to Prevent Proximal Junctional Complications: A Finite Element Study.

The management strategies of thoracolumbar (TL) burst fractures include posterior, anterior, and combined approaches. However, the rigid constructs pose a risk of proximal junctional failure. In this study, we aim to systemically evaluate the biomechanical performance of different TL reconstruction constructs using finite element analysis. Furthermore, we investigate the motion and the stress on the proximal junctional level adjacent to the constructs. We used a T10-L3 finite element model and simulated L1 burst fracture. Reconstruction with posterior instrumentation (PI) alone (U2L2 and U1L1+(intermediate screw) and three-column spinal reconstruction (TCSR) constructs (U1L1+PMMA and U1L1+Cage) were compared. Long-segment PI resulted in greater global motion reduction compared to constructs with short-segment PI. TCSR constructs provided better stabilization in L1 compared to PI alone. Decreased intradiscal and intravertebral pressure in the proximal level were observed in U1L1+IS, U1L1+PMMA, and U1L1+Cage compared to U2L2. The stress and strain energy of the pedicle screws decreased when anterior reconstruction was performed in addition to PI. We showed that TCSR with anterior reconstruction and SSPI provided sufficient immobilization while offering additional advantages in the preservation of physiological motion, the decreased burden on the proximal junctional level, and lower risk of implant failure.

Mechanical Stretch Induced Osteogenesis on Human Annulus Fibrosus Cells through Upregulation of BMP-2/6 Heterodimer and Activation of P38 and SMAD1/5/8 Signaling Pathways.

Degenerative disc disease (DDD) is an important cause of low back pain. Repetitive tensile stress from the daily motion of the spine predisposes it to injury of the annulus fibrosus (AF) which causes IVD degeneration. This study aims to determine the causal relationship between mechanical stretch and osteogenesis in the AF cells of IVD as affected by bone morphogenic proteins (BMPs), specifically BMP-2/6 heterodimers. Our results found that 15% tensile stress (high cyclic stretching, HCS) may induce the expression of osteogenesis-related markers (Runx2, osterix) by upregulating BMP-2/6 heterodimeric ligands and their receptors on the human AF cell line. HCS also induced transient phosphorylation of p38 mitogen-activated protein (MAP) kinase and SMAD1/5/8. Neutralizing antibodies to the BMP-2/6 receptor (ALK3) blocked the expression of Runx2 and osterix, as well as the phosphorylation of p38 and SMAD1/5/8. In addition, treatment with a p38 MAPK inhibitor (SB203580) or siRNA to neutralize the effects of SMAD1/5/8 suppressed tensile stress-induced Runx2 and osterix expression. Mechanical stretching induces activation of p38 MAP kinase and SMAD1/5/8 signaling pathways, followed by the upregulation of BMP-2/6 heterodimer expression, thereby stimulating osteogenic Runx2 and osterix expression on AF cells. HCS may accelerate the progression of IVD degeneration by promoting an osteogenic response.

Mechanical Stretch-Induced NLRP3 Inflammasome Expression on Human Annulus Fibrosus Cells Modulated by Endoplasmic Reticulum Stress.

Excessive mechanical loading is a major cause of spinal degeneration, typically originating from a tear in the annulus fibrosus (AF). Endoplasmic reticulum (ER) stress and NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome have been implicated in the pathogenesis of intervertebral disc (IVD) degeneration. However, the causal relationship between the mechanical stretching of AF cells and the NLRP3 inflammasome response associated with ER stress remains scarce. To elucidate the pathogenesis and regulatory mechanisms of mechanical stretch-induced IVD degeneration, human AF cell lines were subjected to different degrees of cyclic stretching to simulate daily spinal movements. Our results indicated that 15% high cyclic stretch (HCS) induced the expression of NLRP3 and interleukin-1 beta (IL-1ß) and was also responsible for the increased expression of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 2 (NOX2) and reactive oxygen species (ROS) in human AF cells. In addition, HCS increased the expression of glucose-regulated protein 78 (GRP78), an ER stress chaperone, which was neutralized with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor. In addition, HCS was found to induce thioredoxin-interacting protein (TXNIP) expression and NLRP3 inflammasome activation, which can be suppressed by si-NOX2 or the NOX2 inhibitor GSK2795039. Consequently, HCS upregulated ER stress and ROS production, leading to increased NLRP3 and IL-1ß expression in human AF cells, and may further accelerate IVD degeneration.

Development of Astaxanthin-Loaded Nanosized Liposomal Formulation to Improve Bone Health.

Astaxanthin is a xanthophyll carotenoid commonly found in marine organisms. Due to its super antioxidative ability, astaxanthin has been widely applied as a human nutraceutical supplement for health benefits. In order to enhance the bioavailability of astaxanthin, we used soybean phosphatidylcholine to encapsulate astaxanthin for liposomal formation. The physical properties of astaxanthin (asta)-loaded liposomes were determined by particle size, encapsulation efficiency and polydispersity index. The results revealed that the particle sizes of asta-loaded liposomes with various concentrations exhibited mean diameters in the range of 109 to 134 nm and had a narrow PDI value. As expected, the entrapment efficiency of liposomes loaded with a low concentration of astaxanthin (0.05 µg/mL) was 89%, and that was reduced to 29% for 1.02 µg/mL asta loading. Alizarin red staining and calcium content measurement showed that there was a significant reduction in calcium deposition for 7F2 osteoblasts treated with asta-loaded liposomes (0.25-1.02 µg/mL) in comparison with the cells treated with drug-free liposomes and mineralization medium (MM). Although liposomal formulation can reduce the cytotoxicity of astaxanthin and possess antioxidant, anti-inflammatory and anti-osteoclastogenic activities in RAW264.7 macrophages, asta-loaded liposomes with high concentrations may suppress ALP activity and mineralization level in 7F2 osteoblasts. Therefore, astaxanthin extract may be able to protect bones against oxidative stress and inflammation through liposomal formulation.

Biomechanical feasibility of semi-rigid stabilization and semi-rigid lumbar interbody fusion: a finite element study.

BACKGROUND: Semi-rigid lumbar fusion offers a compromise between pedicle screw-based rigid fixation and non-instrumented lumbar fusion. However, the use of semi-rigid interspinous stabilization (SIS) with interspinous spacer and ligamentoplasty and semi-rigid posterior instrumentation (SPI) to assist interbody cage as fusion constructs remained controversial. The purpose of this study is to investigate the biomechanical properties of semi-rigidly stabilized lumbar fusion using SIS or SPI and their effect on adjacent levels using finite element (FE) method. METHOD: Eight FE models were constructed to simulate the lumbosacral spine. In the non-fusion constructs, semi-rigid stabilization with (i) semi-rigid interspinous spacer and artificial ligaments (PD-SIS), and (ii) PI with semi-rigid rods were simulated (PD + SPI). For fusion constructs, the spinal models were implanted with (iii) PEEK cage only (Cage), (iv) PEEK cage and SIS (Cage+SIS), (v) PEEK cage and SPI (Cage+SPI), (vi) PEEK cage and rigid PI (Cage+PI). RESULT: The comparison of flexion-extension range of motion (ROM) in the operated level showed the difference between Cage+SIS, Cage+SPI, and Cage+PI was less than 0.05 degree. In axial rotation, ROM of Cage+SIS were greater than Cage+PI by 0.81 degree. In the infrajacent level, while Cage+PI increased the ROM by 24.1, 27,7, 25.9, and 10.3% and Cage+SPI increased the ROM by 26.1, 30.0, 27.1, and 10.8% in flexion, extension, lateral bending and axial rotation respectively, Cage+SIS only increased the ROM by 3.6, 2.8, and 11.2% in flexion, extension, and lateral bending and reduced the ROM by 1.5% in axial rotation. The comparison of the von Mises stress showed that SIS reduced the adjacent IVD stress by 9.0%. The simulation of the strain energy showed a difference between constructs less than 7.9%, but all constructs increased the strain energy in the infradjacent level. CONCLUSION: FE simulation showed semi-rigid fusion constructs including Cage+SIS and Cage+SPI can provide sufficient stabilization and flexion-extension ROM reduction at the fusion level. In addition, SIS-assisted fusion resulted in less hypermobility and less von Mises stress in the adjacent levels. However, SIS-assisted fusion had a disadvantage of less ROM reduction in lateral bending and axial rotation. Further clinical studies are warranted to investigate the clinical efficacy and safety of semi-rigid fusions.

Sitting Posture during Prolonged Computer Typing with and without a Wearable Biofeedback Sensor.

Prolonged sitting combined with an awkward posture might contribute to the increased risks of developing spinal pain. Maintaining an upright sitting posture is thus often suggested, especially nowadays when people spend longer periods in the sitting posture for occupational or leisure activities. Many types of assistive devices are commercially available to help computer users maintain an upright sitting posture. As the technology advances, wearable sensors that use microelectromechanical technology are designed to provide real-time biofeedback and promote adjusting posture actively. However, whether such wearable biofeedback sensors could assist adjusting sitting posture in computer users during prolonged typing remains unknown. This study aimed to investigate the effects of a wearable biofeedback sensor on maintaining an upright sitting posture. Twenty-one healthy young adults were recruited and performed a 1-h computer typing task twice, with and without using the active biofeedback device. The sagittal spinal posture during computer typing was measured using a three-dimensional motion analysis system. Using the wearable biofeedback sensor significantly decreased the neck flexion (p < 0.001), thoracic kyphotic (p = 0.033), and pelvic plane (p = 0.021) angles compared with not using the sensor. Computer users and sedentary workers may benefit from using wearable biofeedback sensors to actively maintain an upright sitting posture during prolonged deskwork.

Comparison of Posterior Fixation Strategies for Thoracolumbar Burst Fracture: A Finite Element Study.

The management of thoracolumbar (TL) burst fractures remained challenging. Due to the complex nature of the fractured vertebrae and the lack of clinical and biomechanical evidence, currently, there was still no guideline to select the optimal posterior fixation strategy for TL burst fracture. We utilized a T10-L3 TL finite element model to simulate L1 burst fracture and four surgical constructs with one- or two-level suprajacent and infrajacent instrumentation (U1L1, U1L2, U2L1, and U2L2). This study was aimed to compare the biomechanical properties and find an optimal fixation strategy for TL burst fracture in order to minimize motion in the fractured level without exerting significant burden in the construct. Our result showed that two-level infrajacent fixation (U1L2 and U2L2) resulted in greater global motion reduction ranging from 66.0 to 87.3% compared to 32.0 to 47.3% in one-level infrajacent fixation (U1L1 and U2L1). Flexion produced the largest pathological motion in the fractured level but the differences between the constructs were small, all within 0.26 deg. Comparisons in implant stress showed that U2L1 and U2L2 had an average 25.3 and 24.8% less von Mises stress in the pedicle screws compared to U1L1 and U1L2, respectively. The construct of U2L1 had better preservation of the physiological spinal motion while providing sufficient range of motion reduction at the fractured level. We suggested that U2L1 is a good alternative to the standard long-segment fixation with better preservation of physiological motion and without an increased risk of implant failure.

Optimization of Three-Level Cervical Hybrid Surgery to Prevent Adjacent Segment Disease: A Finite Element Study.

Hybrid surgery (HS) allows surgeons to tailor fusion and arthroplasty in the treatment of multiple-level cervical disc degeneration. However, the decision making of selecting either ACDF or ADR for each level in three-level HS remains controversial and has not been fully investigated. This study was aimed to optimize three-level cervical hybrid constructs by systematically investigating their biomechanical properties and their effect on adjacent levels. A finite element model of cervical spine (C2-C7) was developed, and eight C3-C6 surgical models including six HS were constructed. The range of motion (ROM) in flexion, extension, lateral bending, and axial rotation under 2.0 Nm moments with 30 N follower load were simulated. The von Mises stress, strain energy at the adjacent intervertebral disc (IVD) and force at the adjacent facet were calculated. The ROM of the hybrid constructs and adjacent levels was close to that of the intact spine. HS with arthroplasty performed at C5-6 had better performance in terms of ROM reduction at the inferior adjacent level (C6-7). Moreover, C-D-D and 3ADR had best performance in reducing the von Mises stress and strain energy at C6-7. All HS reduced the facet burden at both C2-3 and C6-7 levels. However, the major drawback of HS revealed here is that the effect of C6-7 protection is at the cost of increased C2-3 IVD burden. In conclusion, we recommend C-D-D and 3ADR for patient with C3-C6 disc degeneration without predisposing C2-3 condition. C-C-D could be a good alternative with a lower medical cost. This analysis guides the decision making in three-level cervical HS before future cadaver studies or human clinical trials.

Effects of IL-1ß, IL-20, and BMP-2 on Intervertebral Disc Inflammation under Hypoxia.

Intervertebral disc (IVD) is an avascular tissue under hypoxic condition after adulthood. Our previous data showed that inflammatory cytokines (interleukin (IL)-1ß), IL-20, and bone morphogenetic protein-2 (BMP-2) play important roles in the healing process after disc injury. In the current study, we investigated whether IL-1ß, IL-20, or BMP-2 modulate the expression of pro-inflammatory cytokines, chemotaxis factor, and angiogenesis factor on IVD cells under hypoxia. IVD cells were isolated from patients with intervertebral disc herniation (HIVD) at the levels of L4-5 and L5-S1. We found that the expression of IL-1ß, IL-20, BMP-2, hypoxia-inducible factor (HIF)-1α, IL-6, IL-8, angiogenetic factor (vascular endothelial growth factor (VEGF)), chemotactic factor (monocyte chemoattractant protein 1 (MCP-1)), and matrix metalloproteinase-3 (MMP-3) was upregulated in IVD cells under hypoxia conditions. In addition, IL-1ß upregulated the expression of pro-inflammatory cytokines (IL-6 and IL-8), VEGF, MCP-1, and disc degradation factor (MMP-3) in IVD cells under hypoxia conditions. IL-20 upregulated MCP-1 and VEGF expression. BMP-2 also upregulated the expression of MCP-1, VEGF, and IL-8 in IVD cells under hypoxia conditions. Treatment with antibody against IL-1ß decreased VEGF and MMP-3 expression, while treatment with IL-20 or BMP-2 antibodies decreased MCP-1, VEGF, and MMP-3 expression. Moreover, IL-1ß modulated both the expression of IL-20 and BMP-2, but IL-20 only modulated BMP-2 either under a hypoxic or normoxic condition. Therefore, we concluded that the inflammation, chemotaxis, matrix degradation, and angiogenesis after disc herniation are influenced by the hypoxic condition and controlled by IL-1ß, IL-20, and BMP-2.

Immediate effects of real-time postural biofeedback on spinal posture, muscle activity, and perceived pain severity in adults with neck pain.

BACKGROUND: Previous studies have investigated various types of postural biofeedback devices on different body regions to improve posture; however, they focused only on healthy adults without a history of chronic musculoskeletal disorders. In addition, those postural biofeedback devices used in previous studies are often designed for experimental research. The designs are usually bulky with many wires, which is not practical for everyday use. RESEARCH QUESTION: The aim of this study was to determine the immediate effect of a commercially available real-time postural biofeedback device on spinal posture, muscle activity, and perceived pain severity in adults with neck pain. METHODS: 21 adults who had chronic or recurrent nonspecific neck pain for more than 3 months and whose pain was induced or aggravated by prolonged computer work were enrolled in this study. Spinal posture (head tilt, neck flexion, cervical and thoracic angles), muscle activity (cervical erector spinae, upper trapezius, and thoracic erector spinae), and self-reported neck and shoulder pain were measured during computer typing tasks, with and without biofeedback. RESULTS: Compared with the non-biofeedback condition, the biofeedback condition significantly decreased neck flexion, upper cervical, and lower thoracic angles and lowered the activity of the cervical erector spinae. Self-reported neck pain was not influenced by the application of biofeedback, but significantly increased over the 1-hour typing task. SIGNIFICANCE: The application of a commercially available wearable real-time biofeedback device improves sitting posture and reduces muscular activity in adults with nonspecific neck pain during computer work. Future studies should examine the long-term effects of wearable real-time postural biofeedback devices for prevention and management of neck pain.

Long Term Survival of Pathological Thoracolumbar Fractures Treated with Vertebroplasty: Analysis Using a Nationwide Insurance Claim Database.

BACKGROUND: There are still debates on the long-term outcome of treating pathological thoracolumbar fractures, including osteoporosis and oncologic problems, using vertebroplasty. METHODS: We collected 8625 patients with pathological thoracolumbar fractures (ICD-9-CM codes 733.13 combined with 805.2 or 805.4) between the years of 2003 to 2013, from the two million random samples from the National Health Insurance Research Database in Taiwan. Survival analysis was conducted to estimate the mortality risks of different treatments, including vertebroplasty (n = 1389), conventional open surgery (n = 1219), or conservative treatment (n = 6017). A multivariable Cox proportional hazard model was constructed for adjustment of age, gender, comorbidities and complications. RESULTS: Crude incidence rate of patients with pathological thoracolumbar fractures in Taiwan gradually increased year by year. Compared with conservative treatment, conventional open surgery and vertebroplasty seemed to improve long-term survival with adjusted hazard ratios (aHR) of 0.80 (95% confidence interval (CI) 0.70-0.93), and 0.87 (95% CI 0.77-0.99), respectively. The survival advantage of vertebroplasty appeared more evident for those aged over 75. However, we were unable to rule out confounding by indication. CONCLUSION: Although conventional open surgery would usually be the best choice for the treatment of patients with pathological thoracolumbar fractures, database information from current real-world practice appears to support vertebroplasty as a viable choice for elderly people over 75 years of age.

MLN4924, a Protein Neddylation Inhibitor, Suppresses the Growth of Human Chondrosarcoma through Inhibiting Cell Proliferation and Inducing Endoplasmic Reticulum Stress-Related Apoptosis.

Chondrosarcoma, a heterogeneous malignant bone tumor, commonly produces cartilage matrix, which generally has no response to conventional therapies. Studies have reported that MLN4924, a NEDD8-activating enzyme inhibitor, achieves antitumor effects against numerous malignancies. In this study, the suppressive effects of MLN4924 on human chondrosarcoma cell lines were investigated using in vitro and in vivo assays, which involved measuring cell viability, cytotoxicity, apoptosis, proliferation, cell cycles, molecule-associated cell cycles, apoptosis, endoplasmic reticulum (ER) stress, and tumor growth in a xenograft mouse model. Our results demonstrated that MLN4924 significantly suppressed cell viability, exhibited cytotoxicity, and stimulated apoptosis through the activation of caspase-3 and caspase-7 in chondrosarcoma cell lines. Furthermore, MLN4924 significantly inhibited cell proliferation by diminishing the phosphorylation of histone H3 to cause G2/M cell cycle arrest. In addition, MLN4924 activated ER stress⁻related apoptosis by upregulating the phosphorylation of c-Jun N-terminal kinase (JNK), enhancing the expression of GRP78 and CCAAT-enhancer-binding protein homologous protein (CHOP, an inducer of endoplasmic ER stress⁻related apoptosis) and activating the cleavage of caspase-4. Moreover, MLN4924 considerably inhibited the growth of chondrosarcoma tumors in a xenograft mouse model. Finally, MLN4924-mediated antichondrosarcoma properties can be accompanied by the stimulation of ER stress⁻related apoptosis, implying that targeting neddylation by MLN4924 is a novel therapeutic strategy for treating chondrosarcoma.

The roles of IL-19 and IL-20 in the inflammation of degenerative lumbar spondylolisthesis.

BACKGROUND: Degenerative lumbar spondylolisthesis (DLS) is a major cause of spinal canal stenosis and is often related to lower back pain. IL-20 is emerging as a potent angiogenic, chemotactic, and proinflammatory cytokine related to several chronic inflammatory bone disorders likes intervertebral disc herniation, rheumatoid arthritis (RA), osteoporosis, and bone fracture. IL-19 also acts as a proinflammatory cytokine in RA. The aim of the present study was to investigate whether IL-19 and IL-20 are involved in DLS and compare three different tissues including disc, facet joint, and ligamentum flavum of patients with DLS to verify which tissue is affected more by inflammation. METHODS: Disc, facet joint and ligamentum flavum from 13 patients with DLS was retrieved, and the expression pattern of IL-19, IL-20, IL-20R1, IL-20R2, TNF-α, IL-1ß, and MCP-1 was evaluated using immunohistochemical staining with specific antibodies. The disc cells were isolated and incubated with IL-19 and IL-20 under CoCl2-mimicked hypoxic conditions to analyze the proinflammatory cytokine expression pattern using real-time quantitative PCR with specific primers. RESULTS: IL-19 and IL-20 were positively stained and accompanied by abundant expression of TNF-α, IL-1ß, and MCP-1 in facet joints of DLS patients. IL-19 and IL-20's receptors (IL-20R1 and IL-20R2) were expressed on chondrocytes and fibrocytes/fibroblasts in facet joint and ligamentum flavum tissues from patients with DLS. There was a significant correlation between the expression of IL-20 and IL-1ß in facet joint. In vitro assay, IL-19 and IL-20 upregulated the expression of IL-1ß, IL-6, TNF-α, IL-8, VEGF, and MCP-1 in primary cultured DLS disc cells under CoCl2-mimicked hypoxic conditions. CONCLUSIONS: IL-19, IL-20, and their receptors as well as proinflammatory cytokines (TNF-α, IL-1ß, and MCP-1) were expressed more in facet joints than the other tissues in patients with DLS; therefore, the etiology of inflammation might be more facet-centric. IL-19 and IL-20 induced proinflammatory cytokine expression in disc cells and might play a role in the pathogenesis of DLS.

Short-segment decompression and fixation for thoracolumbar osteoporotic fractures with neurological deficits.

Objective We assessed our results of short-segment decompression and fixation for osteoporotic thoracolumbar fractures with neurological deficits. Methods We evaluated 20 elderly patients (age, 60-89 years; mean, 73.2 years) with osteoporotic thoracolumbar fractures and neurological deficits. They underwent short-segment decompression and fixation and followed up for 40.6 (range, 24-68) months. A visual analog scale (VAS) and the Oswestry Disability Index (ODI) were used to measure back pain and disability. We also analyzed patients' radiologic findings and neurological status. Perioperative and postoperative complications were recorded. Results At the latest follow-up, the average VAS score for back pain and ODI scores had significantly improved. The radiologic assessment showed significant improvements in local kyphosis, anterior vertebral height, and the vertebral wedge angle compared with the original measures. Neurological function also improved in 18 of 20 patients. No major complications occurred perioperatively. Our techniques included preservation of the posterior ligament complex, decortication of facet joints for fusion, no tapping to increase the screw insertional torque, pre-contouring of the rods according to the "adaptive" curve obtained from postural reduction, and postoperative spinal bracing. Conclusions Posterior short-segment decompression and fixation could be an effective surgical option for osteoporotic thoracolumbar burst fractures with neurological deficits.

Rare occurrence of inflammatory bowel disease in a cohort of Han Chinese ankylosing spondylitis patients- a single institute study.

Despite a high prevalence of ankylosing spondylitis (AS) in Han Chinese, the clinical experience remains very limited in the extra-articular presentation of inflammatory bowel disease (IBD). A monocentric retrospective study was performed for the AS-associated IBD manifestation. This study analyzed AS patients fulfilling the 1984 revised New York diagnostic criteria, excluding those who had the onset of IBD before or concurrently with the diagnosis of AS, for their demographic, clinical, laboratory, radiological, pathological and medication data, particularly in the usage of anti-TNF monoclonal antibody. Among 988 AS patients with 19.8% female, 4 (0.4%) had the overt IBD presentation, one female and 3 male aged 28 to 47 years (38.8 ± 4.6), all ulcerative colitis with the characteristic histopathological findings. At the onset of colitis, all had a long-term disease duration of 10 to 25 years (17.5 ± 6.5) and high BASDAI 7.5 to 8.8 (8.2 ± 0.5) with the hip joint involvement. There were recurrent flares of colitis despite the treatment with corticosteroids and messalazopyrin/salazopyrin, and no relapses of IBD were observed for 6.0 ± 1.1 years after the adalimumab (ADA) therapy. In this retrospective cohort, we demonstrate the rarity of AS-associated IBD manifestation in Han Chinese with a beneficent effect from the ADA therapy.