Hua-Qing Zhang

Background Intervertebral disc (IVD) degeneration (IDD) is a leading cause of low back pain, with limited treatment options. The degenerative disc’s harsh microenvironment promotes nucleus pulposus-derived mesenchymal stem cells (NP-MSCs) death and hinders self repair. Mesencephalic astrocyte-derived neurotrophic factor (MANF), an atypical neurotrophic factor, has protective effects in degenerative diseases. However, its role in IDD is unclear. Methods Assessment of MANF expression was conducted in both human nucleus pulposus tissues and a rat IVD puncture model. An in vitro model of degeneration was established by acid treatment of NP-MSCs, and the functional role of MANF was explored through its knockdown and overexpression. RNA sequencing was employed to identify downstream targets. The therapeutic potential of MANF-overexpressing NP-MSCs was evaluated in a rat puncture model. Results MANF expression was markedly downregulated in degenerated IVD tissues from both human patients and rat models. Correspondingly, in vitro experiments demonstrated that MANF knockdown exacerbated, while its overexpression mitigated, acid-induced apoptosis of NP-MSCs. Mechanistically, MANF attenuated mitochondrial dysfunction and ER stress of NP-MSCs under acidic conditions by maintaining MAM integrity, as demonstrated by the complete abolition of this protection upon treatment with the MAM uncoupler FATE1. Transcriptomic analysis and subsequent validation identified receptor expression-enhancing protein 1 (REEP1) as a critical downstream effector through which MANF safeguards MAM integrity. We further elucidated that MANF upregulates REEP1 expression by directly inhibiting miR-33b-5p. In vivo, transplantation of MANF-overexpressing NP-MSCs effectively attenuated IDD in a rat model. Conclusion MANF protected NP-MSCs from acidosis by sustaining MAM integrity via the MiR-33b-5p/REEP1 axis. These findings reveal MANF’s mechanism and therapeutic potential for IDD.

Objective This study compared single-segment and multi-segment lumbar vertebral bone quality (VBQ) score measurements in assessing bone mineral density (BMD), diagnosing osteoporosis, and predicting thoracolumbar fragility fractures to determine the more accurate and practical method. Methods A retrospective analysis was conducted on patients who underwent lumbar spine MRI and dual-energy X-ray absorptiometry (DEXA) at the First Affiliated Hospital of Anhui Medical University between August 2019 and August 2023. After applying inclusion and exclusion criteria, 210 patients were enrolled(86 with fractures, 124 without). On sagittal T1-weighted MRI images, regions of interest (ROI) were placed within the trabecular bone from L1 to S1 and adjacent cerebrospinal fluid (CSF). VBQ was calculated as the ratio of vertebral trabecular bone signal intensity (SI) to CSF SI. Both single-segment (VBQ_L1, VBQ_L2, VBQ_L3, VBQ_L4, VBQ_L5, VBQ_S1) and multi-segment (VBQ_L1~L4, VBQ_L1~L5, VBQ_L1~S1) VBQ scores were evaluated. Correlations between VBQ and DEXA-derived BMD (BMD_DEXA/T-score) were analyzed. Diagnostic accuracy for osteoporosis and fragility fractures was assessed using receiver operating characteristic (ROC) curves. Results All VBQ scores significantly correlated with BMD_DEXA/T-score. Among single segments, VBQ_L2 showed the strongest correlation with T-score (r = −0.345) and best AUC for osteoporosis and low BMD prediction. Among multi-segment scores, VBQ_L1~L4 had the strongest correlation (r = −0.319) and best overall diagnostic performance (low BMD AUC = 0.696; fracture AUC = 0.580). Conclusion VBQ scores demonstrated weak-to-moderate correlations with BMD_DEXA and limited diagnostic utility (all AUC < 0.70). Among single segments, L2 performed slightly better, whereas the L1 ~ L4 average was marginally superior among multi-segment approaches. VBQ should therefore serve as a supplementary screening adjunct to DEXA or CT, rather than a stand-alone diagnostic tool, especially for patients who have undergone lumbar MRI but cannot access DEXA/CT.

Purpose This study aims to design novel cortical bone trajectories for the lower thoracic vertebrae that traverse the anterior, middle, and posterior columns. We seek to establish novel theoretical guidelines and placement strategies to optimize the trajectory of CBT screws in osteoporotic patients. Methods Five different diameters of CBT screws, ranging from 3.5 mm to 5.5 mm, were designed. The tip of the simulated screw was aimed at the anterior half of the vertebral body, with appropriate cephalad and lateral angles. Screw placement was simulated using Mimics software, and key parameters—maximum screw length, cephalad angle, lateral angle, and bone density along the screw path—were measured. We then compared screw placement parameters across different spinal segments and screw specifications, analyzing factors influencing the success of three-column CBT screw placement. Results Successful simulation of three-column CBT screw placement in the lower thoracic spine (T9-12) was achieved with a high success rate. As screw diameter increased, the maximum screw length decreased, while cephalad and lateral angles increased. The HU values along the trajectories of the three-column CBT screws were significantly higher than those of traditional thoracic pedicle screw trajectories (p < 0.05). Key factors affecting the success of three-column CBT screw placement were pedicle width and screw diameter. Conclusion By adjusting the entry point and modifying the cephalad and lateral angles, the concept of three-column CBT screw fixation can be effectively applied to the lower thoracic vertebrae.

Loss of nucleus pulposus (NP) cells is as one of the primary factors initiating intervertebral disc (IVD) degeneration (IVDD); however, the intrinsic physiological mechanisms of endogenous NP-derived stem cell (NPSC)-based therapy in IVDD remain poorly understood. Disturbed iron homeostasis is commonly observed in degenerative diseases, and an acidic microenvironment has been considered a crucial factor in IVDD. The molecular mechanism of ferroptosis in acidic microenvironments during IVDD has not been reported. Herein, we intended to investigate whether acidic conditions can induce ferroptosis in NPSCs and explore the mechanism of IVDD progression through NCOA4-mediated ferritinophagy, which is a type of selective autophagy mediating ferroptosis. The role of ring-box 1 (RBX1) in NCOA4-mediated ferritinophagy in NPSC ferroptosis and IVDD pathogenesis was also explored. First, clinical epidemiology research revealed that a reduction in serum ferritin level was an independent risk factor for IVDD. We then demonstrated that ferroptosis progressively increased in human NP tissues as IVDD advanced and the acidic conditions induced ferroptosis-associated decline in cell viability, reactive oxygen species accumulation, and extracellular matrix degradation in human NPSCs. In an acidic microenvironment, ferroptosis is promoted due to enhanced NCOA4-mediated ferritinophagy in NPSCs. A mechanistic study demonstrated that RBX1-mediated ubiquitination modulated NCOA4 expression and the inhibition of RBX1 promoted ferroptosis through NCOA4-mediated ferritinophagy in the human NPSCs. Our in vivo study further illustrated that RBX1 overexpression ameliorated ferroptotic effects on IVDD progression by suppressing NCOA4-mediated ferritinophagy. Results demonstrated the modulating role of RBX1 in NCOA4-mediated ferritinophagy and NPSC ferroptosis, providing valuable insights into the potential application of endogenous stem cell–based IVD self-repair and self-regeneration for IVDD treatment.

Objective: This study assessed biomechanical properties of pedicle screws enhanced or revised with 3 materials. We aimed to compare the efficacy of these materials in pedicle augmentation and revision.Methods: One hundred twenty human cadaveric vertebrae were utilized for in vitro testing. Vertebrae bone density was evaluated. Allograft bone particles (ABP), calcium phosphate cement (CPC), and demineralized bone matrix (DBM) were used to augment or revise pedicle screw. Post the implantation of pedicle screws, parameters such as insertional torque, pullout strength, cycles to failure and failure load were measured using specialized instruments.Results: ABP, CPC, and DBM significantly enhanced biomechanical properties of the screws. CPC augmentation showed superior properties compared to ABP or DBM. ABP-augmented screws had higher cycles to failure and failure loads than DBM-augmented screws, with no difference in pullout strength. CPC-revised screws exhibited similar strength to the original screws, while ABP-revised screws showed comparable cycles to failure and failure loads but lower pullout strength. DBM-revised screws did not match the original screws’ strength.Conclusion: ABP, CPC, and DBM effectively improve pedicle screw stability for pedicle augmentation. CPC demonstrated the highest efficacy, followed by ABP, while DBM was less effective. For pedicle revision, CPC is recommended as the primary choice, with ABP as an alternative. However, using DBM for pedicle revision is not recommended.

Objective: Hounsfield units (HU), vertebral bone quality (VBQ), and bone mineral density (BMD) can all serve as predictive indicators for thoracolumbar fragility fractures. This study aims to explore which indicator provides better risk prediction for thoracolumbar fragility fractures.Methods: Patients who have received medical attention from The First Affiliated Hospital of Anhui Medical University for thoracolumbar fragility fractures were selected. A total of 78 patients with thoracolumbar fragility fractures were included in the study. To establish a control group, 78 patients with degenerative spinal diseases were matched to the fracture group on the basis of gender, age, and body mass index. The lumbar vertebral HU, the VBQ, and the BMD were obtained for all the 156 patients through computed tomography, magnetic resonance imaging, and dual-energy x-ray absorptiometry (DEXA). The correlations among these parameters were analyzed. The area under curve (AUC) analysis was employed to assess the predictive efficacy and thresholds of lumbar vertebral HU, VBQ, and BMD in relation to the risk of thoracolumbar fragility fractures.Results: Among the cohort of 156 patients, lumbar vertebral HU exhibited a positive correlation with BMD (p < 0.01). Conversely, VBQ showed a negative correlation with HU, BMD (p < 0.05). HU and BMD displayed a favorable predictive efficacy for thoracolumbar fragility fractures (p < 0.01), with HU (AUC = 0.863) showcasing the highest predictive efficacy, followed by the DEXA-measured BMD (AUC = 0.813). VBQ (AUC = 0.602) ranked lowest among the 3 indicators. The thresholds for predicting thoracolumbar fragility fractures were as follows: HU (88),VBQ (3.37), and BMD (0.81).Conclusion: All 3 of these indicators, HU, VBQ, and BMD, can predict thoracolumbar fragility fractures. Notably, lumbar vertebral HU exhibits the highest predictive efficacy, followed by the BMD obtained through DEXA scanning, with VBQ demonstrating the lowest predictive efficacy.

Background C1 transpedicular screw (C1TS) placement provided satisfactory pullout resistance and 3D stability, but its application might be limited in patients with basilar invagination (BI) due to the high incidences of the atlas anomaly and vertebral artery (VA) variation. However, no study has explored the classifications of C1 posterior arch variations and investigated their indications and ideal insertion trajectories for C1TS in BI. Purpose To investigate the bony and surrounding arterial characteristics of the atlas, classify posterior arch variations, identify indications for C1TS, evaluate ideal insertion trajectories for C1TS in BI patients without atlas occipitalization (AO), and compare them with those without BI and AO as control. Methods A total of 130 non-AO patients with and without BI (52 patients and 78 patients, respectively) from two medical centers were included at a 1:1.5 ratio. The posterior arch variations were assessed using a modified C1 morphological classification. Comparisons regarding the bony and surrounding arterial characteristics, morphological classification distributions, and ideal insertion trajectories between BI and control groups were performed. The subgroup analyses based on different morphological classifications were also conducted. In addition, the factors possibly affecting the insertion parameters were investigated using multiple linear regression analyses. Results The BI group was associated with significantly smaller lateral mass height and width, sagittal length of posterior arch, pedicle height, vertical height of posterior arch, and distance between VA and VA groove (VAG) than control group. Four types of posterior arch variations with indications for different screw placement techniques were classified; Classifications I and II were suitable for C1TS. The BI cohort showed a significantly lower rate of Classification I than the control cohort. In the BI group, the subgroup of Classification I had significantly larger distance between the insertion point (IP) and inferior aspect of the posterior arch. In addition, it had the narrowest width along ideal screw trajectory, but a significantly more lateral ideal mediolateral angle than the subgroup of Classification II. Multiple linear regression indicated that the cephalad angle was significantly associated with the diagnosis of BI (B = 3.708, P < 0.001) and sagittal diameter of C1 (B = 3.417, P = 0.027); the ideal mediolateral angle was significantly associated with BMI (B = 0.264, P = 0.031), sagittal diameter of C1 (B = − 4.559, P = 0.002), and pedicle height (B = − 2.317, P < 0.001); the distance between the IP and inferior aspects of posterior arch was significantly associated with age (B = − 0.002, P = 0.035), BMI (B = − 0.007, P = 0.028), sagittal length of posterior arch (B = − 0.187, P = 0.032), pedicle height (B = − 0.392, P < 0.001), and middle and lower parts of posterior arch (B = 0.862, P < 0.001). Conclusion The incidence of posterior arch variation in BI patients without AO was remarkably higher than that in control patients. The insertion parameters of posterior screws were different between the morphological classification types in BI and control groups. The distance between VA V3 segments and VAG in BI cohort was substantially smaller than that in control cohort. Preoperative individual 3D computed tomography (CT), CT angiography and intraoperative navigation are recommended for BI patients receiving posterior screw placement.

Objective: Patients with basilar invagination (BI) had high incidences of vertebral variations and high-riding vertebral artery (HRVA) that might restrict the use of pedicle or pars screw and increase the use of translaminar screw on axis. Here, we conducted a radiographic study to investigate the feasibility of translaminar screws and the bone quality of C2 laminae in patients with BI, which were compared with those without BI as control to provide guidelines for safe placement.Methods: In this study, a total of 410 patients (205 consecutive patients with BI and 205 matched patients without BI) and 820 unilateral laminae of the axis were included at a 1:1 ratio. Comparisons with regard to insertion parameters (laminar length, thickness, angle, and height) for C2 translaminar screw placement and Hounsfield unit (HU) values for the assessment of the appropriate bone mineral density of C2 laminae between BI and control groups were performed. Besides, the subgroup analyses based on the Goel A and B classification of BI, HRVA, atlas occipitalization, and C2/3 assimilation were also carried out. Furthermore, the factors that might affect the insertion parameters and HU values were explored through multiple linear regression analyses.Results: The BI group showed a significantly smaller laminar length, thickness, height, and HU value than the control group, whereas no significant difference was observed regarding the laminar angle. By contrast, the control group showed significantly higher rates of acceptability for unilateral and bilateral translaminar screw fixations than the BI group. Subgroup analyses showed that the classification of Goel A and B, HRVA, atlas occipitalization, and C2/3 assimilation affected the insertion parameters except the HU values. Multiple linear regression indicated that the laminar length was significantly associated with the male gender (B = 0.190, p < 0.001), diagnoses of HRVA (B = -0.109, p < 0.001), Goel A (B = -0.167, p < 0.001), and C2/3 assimilation (B = -0.079, p = 0.029); the laminar thickness was significantly associated with the male gender (B = 0.353, p < 0.001), diagnoses of HRVA (B = -0.430, p < 0.001), Goel B (B = -0.249, p = 0.026), and distance from the top of odontoid to the Chamberlain line (B = -0.025, p = 0.003); laminar HU values were significantly associated with age (B = -2.517, p < 0.001), Goel A (B = -44.205, p < 0.001), Goel B (B = -25.704, p = 0.014), and laminar thickness (B = -11.706, p = 0.001).Conclusion: Patients with BI had narrower and smaller laminae with lower HU values and lower unilateral and bilateral acceptability for translaminar screws than patients without BI. Preoperative 3-dimensional computed tomography (CT) and CT angiography were needed for BI patients.