Evaluation of the modified MRI vertebral bone quality score for bone quality in lumbar degenerative disorders.

OBJECTIVE: The traditional VBQ scoring method may lead to overestimation due to the concentration of intravertebral fat and vascular structures in the posterior half of vertebral bodies, potentially resulting in false-positive outcomes. This study aims to modify the measurement method of VBQ score (Modified-VBQ) and evaluate its effectiveness in evaluating bone quality of lumbar degenerative diseases. METHODS: Retrospective analysis was conducted on clinical data from patients undergoing lumbar surgery for degenerative diseases between September 2022 and September 2023. Preoperative lumbar t1-weighted Magnetic resonance imaging was used for both modified and traditional VBQ scoring. Computed tomography (CT) images and dual-energy X-ray absorptiometry (DEXA) data were collected through the picture archiving and communication system. The effectiveness of the modified VBQ score was evaluated, considering P < 0.05 as statistically significant. RESULTS: The study included 212 patients, revealing a significant difference between the modified VBQ and VBQ scores (P < 0.0001). Notably, patients with a history of hyperlipidemia exhibited a significant difference between the two scores (P = 0.0037). The area under the ROC curve (AUC) for the modified VBQ was 0.86, surpassing the VBQ score (AUC = 0.74). Linear regression analysis demonstrated a moderate to strong correlation between the modified VBQ and DEXA T-score (r = - 0.49, P < 0.0001) and a high correlation with CT Hounsfield units (HU) values (r = - 0.60, P < 0.0001). CONCLUSION: The modified VBQ score provides a simple, effective, and relatively accurate means of assessing bone quality in lumbar degenerative diseases. Preoperative implementation of the modified VBQ score facilitates rapid screening for patients with abnormal bone quality.

Baicalin Antagonizes Prostate Cancer Stemness via Inhibiting Notch1/NF-κB Signaling Pathway.

OBJECTIVE: To investigate the molecular mechanisms underlying the effect of baicalin on prostate cancer (PCa) progression both in vivo and in vitro. METHODS: The in situ PCa stem cells (PCSCs)-injected xenograft tumor models were established in BALB/c nude mice. Tumor volume and weight were respectively checked after baicalin (100 mg/kg) treatment. Hematoxylin-eosin (HE) staining was used to observe the growth arrest and cell necrosis. mRNA expression levels of acetaldehyde dehydrogenase 1 (ALDH1), CD44, CD133 and Notch1 were determined by reverse transcription-polymerase chain reaction. Protein expression levels of ALDH1, CD44, CD133, Notch1, nuclear factor κB (NF-κB) P65 and NF-κB p-P65 were detected by Western blot. Expression and subcellular location of ALDH1, CD44, CD133, Notch1 and NF-κB p65 were detected by immunofluorescence analysis. In vitro, cell cycle distribution and cell apoptosis of PC3 PCSCs was assessed by flow cytometry after baicalin (125 µmol/L) treatment. The migration and invasion abilities of PCSCs were assessed using Transwell assays. Transmission electron microscopy scanning was utilized to observe the structure and autophagosome formation of baicalin-treated PCSCs. In addition, PCSCs were infected with lentiviruses expressing human Notch1. RESULTS: Compared with the control group, the tumor volume and weight were notably reduced in mice treated with 100 mg/kg baicalin (P<0.05 or P<0.01). Histopathological analysis showed that baicalin treatment significantly inhibited cell proliferation and promoted cell apoptosis. Furthermore, baicalin treatment reduced mRNA and protein expression levels of CD44, CD133, ALDH1, and Notch1 as well as the protein expression of NF-κB p-P65 in the xenograft tumor (P<0.01). In vitro, the cell proliferation of PCSCs was significantly attenuated after treatment with 125 µmol/L baicalin for 72 h (P<0.01). The cell migration and invasion rates were decreased following treatment with baicalin for 48 and 72 h (P<0.01). Baicalin notably induced cell apoptosis and seriously damaged the structure of PCSCs. The mRNA and protein expressions of CD133, CD44, ALDH1 and Notch1 in PCSCs were significantly downregulated following baicalin treatment (P<0.01). Importantly, the inhibitory effects of baicalin on PCa progression and stemness were reversed by Notch1 overexpression (P<0.05 or P<0.01). CONCLUSION: Mechanistically, baicalin exhibited a potential therapeutic effect on PCa via inhibiting the Notch1/NF-κB signaling pathway and its mediated cancer stemness.

Dihydroorotate dehydrogenase regulates ferroptosis in neurons after spinal cord injury via the P53-ALOX15 signaling pathway.

BACKGROUND: Spinal cord injury (SCI) is a highly disabling condition in spinal surgery that leads to neuronal damage and secondary inflammation. Ferroptosis is a non-apoptotic type of cell death that has only recently been identified, which is marked primarily by iron-dependent and lipid-derived reactive oxygen species accumulation, and accompanied by morphological modifications such as mitochondrial atrophy and increase in membrane density. Dihydroorotate dehydrogenase (DHODH) is a powerful inhibitor of ferroptosis and has been demonstrated to inhibit cellular ferroptosis in tumor cells, but whether it can inhibit neuronal injury following spinal cord injury remains ambiguous. METHODS: In this study, the effect of DHODH on neuronal ferroptosis was observed in vivo and in vitro using a rat spinal cord injury model and erastin-induced PC12 cells, respectively. A combination of molecular and histological approaches was performed to assess ferroptosis and explore the possible mechanisms in vivo and in vitro. RESULTS: First, we confirmed the existence of neuronal ferroptosis after spinal cord injury and that DHODH attenuates neuronal damage after spinal cord injury. Second, we showed molecular evidence that DHODH inhibits the activation of ferroptosis-related molecules and reduces lipid peroxide production and mitochondrial damage, thereby reducing neuronal ferroptosis. Further analysis suggests that P53/ALOX15 may be one of the mechanisms regulated by DHODH. Importantly, we determined that DHODH inhibits ALOX15 expression by inhibiting P53. CONCLUSIONS: Our findings reveal a novel function for DHODH in neuronal ferroptosis after spinal cord injury, suggesting a unique therapeutic target to alleviate the disease process of spinal cord injury.

Low lumbar multifidus muscle status and bone mineral density are important risk factors for adjacent segment disease after lumbar fusion: a case-control study.

BACKGROUND: The quantity and quality of the paraspinal muscles are important factors that lead to spinal diseases. However, the role of paraspinal muscles in the pathogenesis of adjacent segment disease (ASD) after lumbar fusion surgery is rarely studied. The purpose of the research is to investigate the relationship between paraspinal muscles and ASD. METHODS: Thirty-three patients with ASD were included, and 33 controls without ASD were matched according to the basic demographic information. Cross-sectional images of the paraspinal muscles at each intervertebral disk level (L1-S1) before the first operation were analyzed, and the cross-sectional area (CSA) and degree of fat infiltration (FI) of the multifidus (MF) muscle and the erector spinae muscle were compared. RESULTS: There was no significant difference in demographic characteristics (P > 0.05) except for the bone mineral density (BMD) (P = 0.037) between the two groups. There were significant differences in the CSA and FI of the lower lumbar multifidus (P < 0.05). The CSA of the MF muscle at L3-L4, FI of the MF muscle at L4-L5 and L5-S1 and BMD were important risk factors for ASD. Among patients who received two-segment fusion for the first time, significant difference was observed in the degree of FI of the MF muscle in the lower lumbar segment (P < 0.05). CONCLUSIONS: The CSA, FI and BMD of the lower lumbar MF muscle were closely related to the occurrence of ASD. The CSA of the MF muscle at L3-L4, the degree of FI of the MF muscle at L4-L5 and L5-S1 and BMD were important risk factors for ASD. The number of fusion segments in the first operation has a certain impact on the above-mentioned conclusions.

Biomechanical effects of interbody cage height on adjacent segments in patients with lumbar degeneration: a 3D finite element study.

OBJECTIVE: To investigate the biomechanical effects of interbody cage height on adjacent segments in patients with lumbar degeneration undergoing transforaminal lumbar interbody fusion (TLIF) surgery, so as to provide references for selection of interbody cage. METHODS: The finite element model of normal lower lumbar spine (L3-S1) was built and validated, then constructed three different degenerative segments in L3-L4, and the cages with different height (8, 10, 12, 14 mm) were implanted into L4-L5 disc. All the twelve models were loaded with pure moment of 7.5 N m to produce flexion, extension, lateral bending and axial rotation motions on lumbar spine, and the effects of cage height on range of motion (RoM) and intervertebral pressure in lumbar spine were investigated. RESULTS: The RoM of adjacent segments and the maximum stress of intervertebral discs increased with the increase in cage height, but this trend was not obvious in mild and moderate degeneration groups. After implantation of four different height cages (8, 10, 12, 14 mm), the RoM of L3/L4 segment reached the maximum during extension. The RoM of mild degeneration group was 2.07°, 2.45°, 2.48°, 2.54°, that of moderate degeneration group was 1.79°, 1.97°, 2.05°, 2.05°, and that of severe degeneration group was 1.43°, 1.66°, 1.74°, 1.74°. The stress of L3-L4 intervertebral disc reached the maximum during flexion. The maximum stress of L3-L4 intervertebral disc was 20.16 MPa, 20.28 MPa, 20.31 MPa and 20.33 MPa in the mild group, 20.58 MPa, 20.66 MPa, 20.71 MPa and 20.75 MPa in the moderate group, and 21.27 MPa, 21.40 MPa, 21.50 MPa and 21.60 MPa in the severe group. CONCLUSION: For patients with mild-to-moderate lumbar degenerative disease who need to undergo TLIF surgery, it is recommended that the height of fusion cage should not exceed the original intervertebral space height by 2 mm, while for patients with severe degeneration, a fusion cage close to the original intervertebral height should be selected as far as possible, and the intervertebral space should not be overstretched.

A study of screw placement to obtain the optimal pull-out resistance of lumbar pedicle screws-analysis of Hounsfield units measurements based on computed tomography.

OBJECTIVE: The screw path of lumbar pedicle screws in the vertebral body has certain variability. It is not clear whether the screw paths in different directions can obtain the same pull-out resistance. This study intends to use CT (Computed Tomography) to measure the Hounsfield unit (HU value) around the screw paths in different parts of the lumbar vertebral body to obtain the bone mineral density value of the corresponding parts which will provide some reference for the direction of lumbar pedicle screw placement. METHODS: This retrospective study included 200 patients with lumbar degenerative diseases selected randomly from the case base and the patient's basic information was recorded. L1-L5 vertebral body was divided equally into the upper, middle and lower 1/3, which was consistent with the three sagittal entry directions of the pedicle screw head tilt, parallel endplate and caudal tilt, and the HU values were measured by CT cross-sectional scanning to indirectly reflect the local bone density values. The paired t-test (randomized block experiment) was used to compare the HU values of the upper, middle and lower 1 / 3 parts, with P < 0.05 being considered statistically significant. RESULTS: Comparison of HU values in different parts of each vertebral body revealed that HU values in the middle 1/3 of the L1,L2 (163.88 ± 58.44 and 152.94 ± 59.45) and in the lower 1/3 of the L4 (149.86 ± 60.18) were higher than in the other two parts of the vertebral body of the same segment(P < 0.0001,P = 0.0069 and P = 0.0024, respectively); According to the results of each stratification, patients with younger age and better bone condition had higher HU values in the middle 1/3 of L1 and L2, and higher HU values in the lower 1/3 of L3, L4 and L5; With the increase of age, the decrease of bone condition and the difference of HU value in each vertebral body gradually decreased. CONCLUSION: Although further follow-up studies are needed, based on the analysis of the statistical results, we speculate that from the perspective of obtaining the best pull-out resistance of the lumbar pedicle screws, the placement direction of L1 and L2 in the sagittal position may be as parallel to the endplate as possible; L3, L4, and L5 may be as appropriate as possible to the tail tilt theoretically.

Iron-Chelating Agent Can Maintain Bone Homeostasis Disrupted by Iron Overload by Upregulating Wnt/Beta-Catenin Signaling.

BACKGROUND: The incidence of osteoporotic fractures is increasing. In this study, we explored the activities of Wnt/ß-catenin signaling in bone tissues with iron accumulation. METHODS: We established rat bipedal walking models (RBWM), and a portion of our RBWM rats were intraperitoneally injected with ferric ammonium citrate, normal saline, and deferoxamine. Bone mineral density was measured with a small animal in vivo imaging system. The protein levels of ferritin, TRAP-5B, RANKL, and OPG in serum were measured by the enzyme-linked immunosorbent assay (ELISA). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to quantify the RNA and protein expression levels of certain regulators involved in Wnt/ß-catenin signaling in bone tissues. RESULTS: In the present study, we established a rat bipedal walking model containing 32 bipedal rats, which were randomly classified into four groups, termed as NS, FAC, FAC+NS, and FAC+DFO. Those three experimental groups with FAC injection had significantly lower bone mineral density (BMD) than the control group NS (P < 0.05). The disruption of bone homeostasis and downregulation of Wnt/ß-catenin signaling were also observed in the three groups with FAC injection. Moreover, after the injection of deferoxamine, those aberrations in samples with FAC injection seemed repaired as test results returning or getting close to normal ranges. CONCLUSION: The osteoporosis could be caused by iron overload, which reduced the bone mineral density by disrupting the homeostasis of bone formation and absorption and attenuating the Wnt/ß-catenin signaling in bone tissues. The deferoxamine had the potential to improve the bone health by reducing the accumulation of iron and increasing the bone mass, which might be a promising therapeutic solution for osteoporosis.

An analysis of clinical risk factors for adolescent scoliosis caused by spinal cord abnormalities in China: proposal for a selective whole-spine MRI examination scheme.

BACKGROUND: Approximately 80% of adolescent scoliosis cases are idiopathic, and some non-idiopathic scoliosis cases caused by spinal cord abnormalities are misdiagnosed as idiopathic scoliosis. This study examined the risk factors for non-idiopathic scoliosis with intramedullary abnormalities, explored the feasibility of whole-spine MRI, and provided a theoretical basis for the routine diagnosis and treatment of adolescent idiopathic scoliosis. METHOD: The clinical data of adolescent scoliosis patients who were admitted to Shanghai Tongren Hospital and Shanghai Changhai Hospital between July 1, 2013, and December 31, 2018, were reviewed. According to the whole-spine MRI results, the patients were divided into either the idiopathic group or the intramedullary abnormality group. Sex, age, main curvature angle, main curvature direction, kyphosis angle, scoliosis type, coronal plane balance, sagittal plane balance, abdominal wall reflex, sensory abnormality, ankle clonus and tendon reflexes were compared between the two groups. Student's t test was used to evaluate the differences in the continuous variables, and the chi-square test was used to evaluate the differences in the categorical variables. Fisher's exact test was applied to detect the difference in the rate of intraspinal anomalies between the groups. Logistic regression was used to evaluate the correlation between the multivariate risk factors and intramedullary abnormalities. RESULT: A total of 714 adolescent scoliosis patients with a mean age of 13.5 (10-18 years) were included in the study, and intramedullary abnormalities were found in 68 (9.5%) patients. There were statistically significant differences in the incidence rates of intramedullary abnormalities between males and females, left and right thoracic curvatures, angular scoliosis and smooth scoliosis, and abnormal abdominal wall reflex and ankle clonus (P < 0.01). Logistic regression showed that the ratios for sex, scoliosis direction, scoliosis type, abdominal wall reflex and ankle clonus were 2.987, 3.493, 4.823, 3.94 and 8.083, respectively. The ROC curve showed a sensitivity of 66.18% and a specificity of 89.01%, and the Youden index corresponding to the optimal critical point was 0.5519. CONCLUSION: Risk factors associated with adolescent scoliosis caused by abnormal intramedullary abnormalities included male sex, thoracic scoliosis on the left side, sharp curvature of the spine, abnormal abdominal wall reflex and ankle clonus. In adolescent scoliosis patients, the incidence of scoliosis caused by intramedullary abnormalities was approximately 9.5%. These clinical indicators suggest that there is a high-risk adolescent scoliosis population who should undergo whole-spinal MRI preoperatively to rule out intramedullary abnormalities.

Robust Drivable Road Region Detection for Fixed-Route Autonomous Vehicles Using Map-Fusion Images.

Environment perception is one of the major issues in autonomous driving systems. In particular, effective and robust drivable road region detection still remains a challenge to be addressed for autonomous vehicles in multi-lane roads, intersections and unstructured road environments. In this paper, a computer vision and neural networks-based drivable road region detection approach is proposed for fixed-route autonomous vehicles (e.g., shuttles, buses and other vehicles operating on fixed routes), using a vehicle-mounted camera, route map and real-time vehicle location. The key idea of the proposed approach is to fuse an image with its corresponding local route map to obtain the map-fusion image (MFI) where the information of the image and route map act as complementary to each other. The information of the image can be utilized in road regions with rich features, while local route map acts as critical heuristics that enable robust drivable road region detection in areas without clear lane marking or borders. A neural network model constructed upon the Convolutional Neural Networks (CNNs), namely FCN-VGG16, is utilized to extract the drivable road region from the fused MFI. The proposed approach is validated using real-world driving scenario videos captured by an industrial camera mounted on a testing vehicle. Experiments demonstrate that the proposed approach outperforms the conventional approach which uses non-fused images in terms of detection accuracy and robustness, and it achieves desirable robustness against undesirable illumination conditions and pavement appearance, as well as projection and map-fusion errors.

Sampling-based real-time motion planning under state uncertainty for autonomous micro-aerial vehicles in GPS-denied environments.

This paper presents a real-time motion planning approach for autonomous vehicles with complex dynamics and state uncertainty. The approach is motivated by the motion planning problem for autonomous vehicles navigating in GPS-denied dynamic environments, which involves non-linear and/or non-holonomic vehicle dynamics, incomplete state estimates, and constraints imposed by uncertain and cluttered environments. To address the above motion planning problem, we propose an extension of the closed-loop rapid belief trees, the closed-loop random belief trees (CL-RBT), which incorporates predictions of the position estimation uncertainty, using a factored form of the covariance provided by the Kalman filter-based estimator. The proposed motion planner operates by incrementally constructing a tree of dynamically feasible trajectories using the closed-loop prediction, while selecting candidate paths with low uncertainty using efficient covariance update and propagation. The algorithm can operate in real-time, continuously providing the controller with feasible paths for execution, enabling the vehicle to account for dynamic and uncertain environments. Simulation results demonstrate that the proposed approach can generate feasible trajectories that reduce the state estimation uncertainty, while handling complex vehicle dynamics and environment constraints.

Downregulation of Notch1 inhibits the invasion of human hepatocellular carcinoma HepG2 and MHCC97H cells through the regulation of PTEN and FAK.

Tumor invasion and metastasis are the main causes of mortality in patients with hepatocellular carcinoma (HCC). Thus, the effective inhibition of these tumorigenic processes is critical in order for HCC therapy to be effective. Previous studies have demonstrated that Notch1 is associated with metastasis in several human malignancies. However, the exact molecular mechanisms underlying the Notch1-mediated induction of the invasion of HCC cells remain poorly understood. In the present study, we demonstrate that, compared to the normal liver cell line, L02, Notch1 is highly expressed in the human HCC cell lines, HepG2 and MHCC97H. Using small interfering RNA (siRNA), we knocked down the expression of Notch1 in the cell lines. Notch1 expression in the HCC cell lines was also measured following transfection with siRNA using RT-PCR and western blot analysis. In addition, a migration and invasion assay was performed to determine the effects of Notch1 knockdown on cell migration and invasion. Our results demonstrated that the downregulation of Notch1 by small interfering RNA (siRNA) significantly inhibited the migration and invasion of both HCC cell lines. Additionally, we demonstrated that the knockdown of Notch1 in both HCC cell lines increased both the total expression of phosphatase and tensin homolog (PTEN) and its phosphorylated form. By contrast, focal adhesion kinase (FAK) and phospho-FAK expression was decreased following Notch1 depletion. Taken together, our data suggest that targeting Notch1 may be a useful therapeutic approach to inhibiting the metastasis of HCC cells.