Factors affecting functional disability in patients with non-specific chronic low back pain: a cross-sectional study.

Background: Knowledge about factors affecting functional disability in patients with non-specific chronic low back pain (NSCLBP) is helpful in guiding treatment, but there has been little systematic research on this topic. This study aimed to identify independent factors contributing to functional disability in NSCLBP patients especially the impact of sagittal parameters and body postures in work, learning, and daily life. Methods: Sociodemographic data, sagittal parameters, Oswestry Disability Index (ODI), Numeric Rating Scale (NRS), and 36-item Short Form Health Survey (SF-36) of NSCLBP patients were collected. Patients were divided into a low-functional disability group (ODI ≤ 20) and a high-functional disability group (ODI > 20), and the ODI was converted to ranked ODI (RODI) accordingly. Sociodemographic data, sagittal parameters, NRS, and SF-36 were compared by univariate analysis between both groups. A correlation analysis of the aforementioned factors with the RODI was conducted. The sociodemographic data and sagittal parameters related to the RODI were analyzed by logistic regression to select potential RODI-associated factors. The level of significance was set at P < 0.05. Results: Age, educational background, daily main posture while working or learning (DMPWL), daily standing time while working or learning (DSTTWL), daily sitting time while resting (DSITR), sacral slope-pelvic tilt (SS-PT), spinosacral angle (SSA), NRS, and SF-36 (except mental health, MH) were different between the two groups (P < 0.05). Correlation analysis showed that they were related to the RODI (P < 0.05). The logistic regression analysis indicated that the regression coefficients of a college degree, postgraduate diploma, DSITR, and SSA were (B = -0.197; P = 0.003), (B = -0.211; P = 0.006), (B = -0.139; P = 0.039), and (B = -0.207; P = 0.001), respectively, and the odds ratio (OR) and 95% confidence interval (CI) were 0.489 (0.308; 0.778), 0.299 (0.125; 0.711), 0.875 (0.772; 0.993), and 0.953 (0.925; 0.981), respectively. Conclusion: Educational background, DSITR, and SSA are independent factors affecting functional disability in NSCLBP patients. NSCLBP patients with a lower educational background, shorter DSITR, or smaller SSA should be taken into account in clinical practice and therapeutic choices. Extending sitting time for rest and the avoidance of a forward-leaning standing position are beneficial for reducing functional disability in NSCLBP.

The effect of phosphorylation on the conformational dynamics and allostery of the association of death-associated protein kinase with calmodulin.

Protein phosphorylation plays an important role in the signal transduction and is capable of regulation of cell activity. The death-associated protein kinase 1 (DAPK1), as a Ser/Thr kinase, interacts with calmodulin (CaM) to regulate apoptotic and autophagic signaling. Autophosphorylation of DAPK1 at Ser308 located at the autoregulatory domain (ARD) blocks CaM binding and inhibits kinase catalytic activity. However, the mechanism underlying the influence of Ser308 phosphorylation (pS308) on the DAPK1 activity remains unclear. Here, we performed multiple, microsecond length molecular dynamics (MD) simulations, the molecular mechanics generalized Born/surface area (MM-GBSA) binding free energy calculations, principal component analysis, and dynamic cross-correlation analysis to unravel the conformational dynamics and allostery of the DAPK1 - CaM interaction triggered by the pS308 at the ARD. MD simulations showed that pS308 affected the conformational stability of the DAPK1 - CaM complex. Further energetic and structural exploration revealed that pS308 weakened the association of the phosphorylated DAPK1 to CaM, which lowered the susceptibility of DAPK1 to be activated by CaM. This result can provide mechanistic insights into the molecular underpinning through which the DAPK1 kinase activity is modulated by the auto-phosphorylation.Communicated by Ramaswamy H. Sarma.

One-stage posterior transpedicular debridement, hemi-interbody and unilateral-posterior bone grafting, and instrumentation for the treatment of thoracic spinal tuberculosis: a retrospective study.

PURPOSE: To investigate the clinical efficacy and feasibility of the surgical treatment of thoracic spinal tuberculosis using one-stage posterior instrumentation, transpedicular debridement, and hemi-interbody and unilateral posterior bone grafting. METHODS: Fifty-six patients with thoracic spinal tuberculosis who underwent surgery performed by a single surgeon between September 2009 and August 2020 were enrolled in this study. Based on data from the erythrocyte sedimentation rate (ESR), Visual Analog Scale (VAS), and Cobb angle before surgery, after surgery, and at the most recent follow-up, clinical effectiveness was assessed using statistical analysis. The variables investigated included operating time, blood loss, complications, neurological function, and hemi-interbody fusion. RESULTS: None of the patients experienced significant surgery-associated complications. At the last follow-up, 23 of the 25 patients (92%) with neurological impairment showed improvement. The thoracic kyphotic angle was significantly decreased from 24.1 ± 9.9° to 13.4 ± 8.6° after operation (P < 0.05), and the angle was 14.44 ± 8.8° at final follow-up (P < 0.05). The Visual Analog Scale significantly decreased from 6.7 ± 1.4 preoperatively to 2.3 ± 0.8 postoperatively (P < 0.05) and finally to 1.2 ± 0.7 at the last follow-up (P < 0.05). Bone fusion was confirmed in 56 patients at 3-6 months postoperatively. CONCLUSIONS: One-stage posterior transpedicular debridement, hemi-interbody and unilateral posterior bone grafting, and instrumentation are effective and feasible treatment methods for thoracic spinal tuberculosis.

Decoding the annulus fibrosus cell atlas by scRNA-seq to develop an inducible composite hydrogel: A novel strategy for disc reconstruction.

Low back pain is one of the most serious public health problems worldwide and the major clinical manifestation of intervertebral disc degeneration (IVDD). The key pathological change during IVDD is dysfunction of the annulus fibrosus (AF). However, due to the lack of an in-depth understanding of AF biology, the methods to reconstruct the AF are very limited. In this study, the mice AF cell atlas were decoded by single-cell RNA sequencing to provide a guide for AF reconstruction. The results first identify a new population of AF cells, fibrochondrocyte-like AF cells, which synthesize both collagen I and collagen II and are potential functional cells for AF reconstruction. According to the dual features of the AF extracellular matrix, a composite hydrogel based on the acylation of methacrylated silk fibroin with methacrylated hyaluronic acid was produced. To obtain the ability to stimulate differentiation, the composite hydrogels were combined with a fibrochondrocyte-inducing supplement. Finally, reconstruction of the AF defects, by the novel AF stem cell-loaded composite hydrogel, could be observed, its amount of chondroid matrices recovered to 31.7% of AF aera which is significantly higher than that in other control groups. In summary, this study decodes the AF cell atlas, based on which a novel strategy for AF reconstruction is proposed.

Magnetic Field Promotes Migration of Schwann Cells with Chondroitinase ABC (ChABC)-Loaded Superparamagnetic Nanoparticles Across Astrocyte Boundary in vitro.

PURPOSE: The clinical outcome of spinal cord injury is usually poor due to the lack of axonal regeneration and glia scar formation. As one of the most classical supporting cells in neural regeneration, Schwann cells (SCs) provide bioactive substrates for axonal migration and release molecules that regulate axonal growth. However, the effect of SC transplantation is limited by their poor migration capacity in the astrocyte-rich central nervous system. METHODS: In this study, we first magnetofected SCs with chondroitinase ABC-polyethylenimine functionalized superparamagnetic iron oxide nanoparticles (ChABC/PEI-SPIONs) to induce overexpression of ChABC for the removal of chondroitin sulfate proteoglycans. These are inhibitory factors and forming a dense scar that acts as a barrier to the regenerating axons. In vitro, we observed the migration of SCs in the region of astrocytes after the application of a stable external magnetic field. RESULTS: We found that magnetofection with ChABC/PEI-SPIONs significantly up-regulated the expression of ChABC in SCs. Under the driven effect of the directional magnetic field (MF), the migration of magnetofected SCs was enhanced in the direction of the magnetic force. The number of SCs with ChABC/PEI-SPIONs migrated and the distance of migration into the astrocyte region was significantly increased. The number of SCs with ChABC/PEI-SPIONs that migrated into the astrocyte region was 11.6- and 4.6-fold higher than those observed for the intact control and non-MF groups, respectively. Furthermore, it was found that SCs with ChABC/PEI-SPIONs were in close contact with astrocytes and no longer formed boundaries in the presence of MF. CONCLUSION: The mobility of the SCs with ChABC/PEI-SPIONs was enhanced along the axis of MF, holding the potential to promote nerve regeneration by providing a bioactive microenvironment and relieving glial obstruction to axonal regeneration in the treatment of spinal cord injury.

Preparation and Assessment of an Individualized Navigation Template for Lower Cervical Anterior Transpedicular Screw Insertion Using a Three-Dimensional Printing Technique.

STUDY DESIGN: Prospective trial. OBJECTIVE: To establish an individualized navigation template for safe and accurate insertion of lower cervical anterior transpedicular screw (ATPS) based on a three-dimensional (3D) printing technique. SUMMARY OF BACKGROUND DATA: Conventional screw insertion manually under fluoroscopy easily leading to deviation of ATPS screw channel, cervical instrumentation procedures demand the need for a precise technique for screw placement. METHODS: Twenty adult cervical spine specimens (10 men and 10 women, with a mean age of 50.29 ±â€Š6.98) were selected for computed tomography pre- and postoperatively. A 3D lower cervical spine model was reconstructed using Mimics software to measure the screw-related parameters and generate a reverse template with optimal screw channel as well as a prototype using 3D printing. Assisted by the navigation template, bilateral ATPS were inserted into the cadavers. RESULTS: The mean outer width and height of pedicle were 5.31 ±â€Š1.23 and 6.78 ±â€Š1.10 mm, respectively. The average length, sagittal, and axial angles of the optimal screw channel obtained through the optimal entry point were 36.34 ±â€Š4.39 mm, 40.67°â€Š±â€Š5.10°, and 93.7°â€Š±â€Š7.96°, respectively. The adjustable safe ranges of sagittal and axial angles were 3.89°â€Š±â€Š1.13° and 5.64°â€Š±â€Š0.97°, respectively. The axial and sagittal accuracies of the 200 screws were 99.5% and 97%, respectively. The average deviations of the actual entry point and the preset opening in the X, Y, and Z axes were 0.39 ±â€Š0.43, 0.21 ±â€Š0.41, and 0.29 ±â€Š0.14 mm, respectively (P > 0.05). CONCLUSION: An individualized ATPS navigation template was developed using Mimics software and 3D printing prototyping, based on computed tomography, for highly accurate screw insertion. LEVEL OF EVIDENCE: 4.

Effect of perfluorotributylamine-enriched alginate on nucleus pulposus cell: Implications for intervertebral disc regeneration.

Various scaffolds have been attempted for intervertebral disc regeneration, but their effectiveness was limited by loss of nutrients within the scaffolds. It has been suggested that the disc is not severely hypoxic and limited availability of oxygen results in disc degeneration. Therefore, a certain oxygen level might be beneficial for disc regeneration, which has not been given enough attention in previous studies. Here, we used perfluorotributylamine (PFTBA) for the first time as an oxygen regulator in alginate scaffold for disc regeneration in vitro and in vivo. We found that the characteristics of alginate were not affected by PFTBA and the oxygen level of the scaffold was regulated. Then, human nucleus pulposus (NP) cells were cultured in the PFTBA-enriched alginates. It was found that PFTBA could promote NP cell survival and proliferation. In addition, 2.5% PFTBA was capable of regulating extracellular matrix (ECM) to a disc-like tissue graft with little effect on the expression of NP cell markers. Finally, 2.5% PFTBA-enriched alginate was found to restore the disc height and the ECM in a mouse disc degeneration model, indicating its beneficial effect on alleviating disc degeneration. These findings highlight the promising application of PFTBA in further intervertebral disc regeneration.

Surgical Incision and Approach in Thoracolumbar Extreme Lateral Interbody Fusion Surgery: An Anatomic Study of the Diaphragmatic Attachments.

STUDY DESIGN: Cadaveric study. OBJECTIVE: To provide anatomical basis for deciding the surgical approach and skin incision in thoracolumbar extreme lateral interbody fusion (XLIF) by delineating the attachment points of diaphragm. SUMMARY OF BACKGROUND DATA: Although the general anatomy of the thoracic diaphragm is well described, the specific attachment points of diaphragm concerned with the XLIF approach is yet to be elaborated. METHODS: Dissections were performed on 21 cases of formalin fixed specimens (12 males, 9 females, a total of 42 sets of data). Special attention was paid to the attachment points of diaphragm on both sides at the midaxillary line (MAL point) and the vertebral level parallel to the MAL point (VL-MAL). The attachment points of diaphragm on the front and back edge of the spinal column (FES point and BES point) were also described. RESULTS: The MAL point of diaphragm muscle lied between the inferior edge of the 10th rib and the superior edge of the 12th rib (20 out of 21 on left, 21 out of 21 on right). VL-MAL lied between L1 and L2 vertebrae level (20 out of 21 on left, 18 out of 21 on right). The attachments on both sides of the vertebral column mainly located between the upper edge of T12 vertebrae and L1-L2 disc (38 out of 42). CONCLUSION: A transthoracic approach should be considered when the target level was above T12 vertebrae, whereas a retroperitoneal approach should be chosen when target level was below L1-L2 disc. If the target level is located between T12 and L1-L2 disc, whether via transthoracic, retropleural, or retroperitoneal approach should be determined according to the conditions of patients and the skill and experience of the surgeon. Incision should be made above the 10th rib for the transthoracic approach and below the 12th rib for the retroperitoneal approach. LEVEL OF EVIDENCE: 4.

Biomechanical study of unilateral pedicle screw combined with contralateral translaminar facet screw in transforaminal lumbar interbody fusion.

BACKGROUND: The biomechanical stability of unilateral pedicle screw (UPS) combined with contralateral translaminar facet screw (TLFS), especially long-term stability, still needs to be compared to traditional UPS or bilateral pedicle screws (BPSs) in details. METHODS: Twenty-four porcine spines (L2-L5) were tested for flexibility with pure moments of 5Nm under intact status and transforaminal lumbar interbody fusion status using UPS+TLFS, UPS or BPS at L3-L4. After short-term (3cycles) and long-term cyclic loading (18,000cycles), the range of motion was obtained and analyzed for single-level constructs in flexion/extension, lateral bending and axial rotation modes. In addition, the relative displacement of contralateral articular processes was recorded in a real time fashion. FINDINGS: The range of motion was significantly reduced in all instrumented constructs. In all movement directions, UPS+TLFS achieved similar range of motion to BPS after short and long-term loading, which were significantly lower than that in UPS. A significantly larger displacement of contralateral articular process was recorded in UPS than UPS+TLFS and BPS during extension/flexion, lateral bending and axial rotation, suggesting its compromised stability. INTERPRETATION: The hybrid construct of UPS+TLFS showed instant and long-term equivalent biomechanical ability to that of traditional BPS, making it an alternative option to BPS that could be less invasive while maintains a stable and effective instrumentation.

Basic study for ultrasound-based navigation for pedicle screw insertion using transmission and backscattered methods.

The purpose of this study was to understand the acoustic properties of human vertebral cancellous bone and to study the feasibility of ultrasound-based navigation for posterior pedicle screw fixation in spinal fusion surgery. Fourteen human vertebral specimens were disarticulated from seven un-embalmed cadavers (four males, three females, 73.14 ± 9.87 years, two specimens from each cadaver). Seven specimens were used to measure the transmission, including tests of attenuation and phase velocity, while the other seven specimens were used for backscattered measurements to inspect the depth of penetration and A-Mode signals. Five pairs of unfocused broadband ultrasonic transducers were used for the detection, with center frequencies of 0.5 MHz, 1 MHz, 1.5 MHz, 2.25 MHz, and 3.5 MHz. As a result, good and stable results were documented. With increased frequency, the attenuation increased (P<0.05), stability of the speed of sound improved (P<0.05), and penetration distance decreased (P>0.05). At about 0.6 cm away from the cortical bone, warning signals were easily observed from the backscattered measurements. In conclusion, the ultrasonic system proved to be an effective, moveable, and real-time imaging navigation system. However, how ultrasonic navigation will benefit pedicle screw insertion in spinal surgery needs to be determined. Therefore, ultrasound-guided pedicle screw implantation is theoretically effective and promising.

Activation of Schwann cells in vitro by magnetic nanocomposites via applied magnetic field.

Schwann cells (SCs) are attractive seed cells in neural tissue engineering, but their application is limited by attenuated biological activities and impaired functions with aging. Therefore, it is important to explore an approach to enhance the viability and biological properties of SCs. In the present study, a magnetic composite made of magnetically responsive magnetic nanoparticles (MNPs) and a biodegradable chitosan-glycerophosphate polymer were prepared and characterized. It was further explored whether such magnetic nanocomposites via applied magnetic fields would regulate SC biological activities. The magnetization of the magnetic nanocomposite was measured by a vibrating sample magnetometer. The compositional characterization of the magnetic nanocomposite was examined by Fourier-transform infrared and X-ray diffraction. The tolerance of SCs to the magnetic fields was tested by flow-cytometry assay. The proliferation of cells was examined by a 5-ethynyl-2-deoxyuridine-labeling assay, a PrestoBlue assay, and a Live/Dead assay. Messenger ribonucleic acid of BDNF, GDNF, NT-3, and VEGF in SCs was assayed by quantitative real-time polymerase chain reaction. The amount of BDNF, GDNF, NT-3, and VEGF secreted from SCs was determined by enzyme-linked immunosorbent assay. It was found that magnetic nanocomposites containing 10% MNPs showed a cross-section diameter of 32.33±1.81 µm, porosity of 80.41%±0.72%, and magnetization of 5.691 emu/g at 8 kOe. The 10% MNP magnetic nanocomposites were able to support cell adhesion and spreading and further promote proliferation of SCs under magnetic field exposure. Interestingly, a magnetic field applied through the 10% MNP magnetic scaffold significantly increased the gene expression and protein secretion of BDNF, GDNF, NT-3, and VEGF. This work is the first stage in our understanding of how to precisely regulate the viability and biological properties of SCs in tissue-engineering grafts, which combined with additional molecular factors may lead to the development of new nerve grafts.

Adipose-derived stromal cells protect intervertebral disc cells in compression: implications for stem cell regenerative disc therapy.

INTRODUCTION: Abnormal biomechanics plays a role in intervertebral disc degeneration. Adipose-derived stromal cells (ADSCs) have been implicated in disc integrity; however, their role in the setting of mechanical stimuli upon the disc's nucleus pulposus (NP) remains unknown. As such, the present study aimed to evaluate the influence of ADSCs upon NP cells in compressive load culture. METHODS: Human NP cells were cultured in compressive load at 3.0MPa for 48 hours with or without ADSCs co-culture (the ratio was 50:50). We used flow cytometry, live/dead staining and scanning electron microscopy (SEM) to evaluate cell death, and determined the expression of specific apoptotic pathways by characterizing the expression of activated caspases-3, -8 and -9. We further used real-time (RT-) PCR and immunostaining to determine the expression of the extracellular matrix (ECM), mediators of matrix degradation (e.g. MMPs, TIMPs and ADAMTSs), pro-inflammatory factors and NP cell phenotype markers. RESULTS: ADSCs inhibited human NP cell apoptosis via suppression of activated caspase-9 and caspase-3. Furthermore, ADSCs protected NP cells from the degradative effects of compressive load by significantly up-regulating the expression of ECM genes (SOX9, COL2A1 and ACAN), tissue inhibitors of metalloproteinases (TIMPs) genes (TIMP-1 and TIMP-2) and cytokeratin 8 (CK8) protein expression. Alternatively, ADSCs showed protective effect by inhibiting compressive load mediated increase of matrix metalloproteinases (MMPs; MMP-3 and MMP-13), disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs; ADAMTS-1 and 5), and pro-inflammatory factors (IL-1beta, IL-6, TGF-beta1 and TNF-alpha). CONCLUSIONS: Our study is the first in vitro study assessing the impact of ADSCs on NP cells in an un-physiological mechanical stimulation culture environment. Our study noted that ADSCs protect compressive load induced NP cell death and degradation by inhibition of activated caspase-9 and -3 activity; regulating ECM and modulator genes, suppressing pro-inflammatory factors and preserving CK8. Consequently, the protective impact of ADSCs found in this study provides an essential understanding and expands our knowledge as to the utility of ADSCs therapy for intervertebral disc regeneration.

Electrically induced brain-derived neurotrophic factor release from Schwann cells.

Regulating the production of brain-derived neurotrophic factor (BDNF) in Schwann cells (SCs) is critical for their application in traumatic nerve injury, neurodegenerative disorders, and demyelination disease in both central and peripheral nervous systems. The present study investigated the possibility of using electrical stimulation (ES) to activate SCs to release BDNF. We found that short-term ES was capable of promoting BDNF production from SCs, and the maximal BDNF release was achieved by ES at 6 V (3 Hz, 30 min). We further examined the involvement of intracellular calcium ions ([Ca2+]i) in the ES-induced BDNF production in SCs by pharmacological studies. We found that the ES-induced BDNF release required calcium influx through T-type voltage-gated calcium channel (VGCC) and calcium mobilization from internal calcium stores, including inositol triphosphate-sensitive stores and caffeine/ryanodine-sensitive stores. In addition, calcium-calmodulin dependent protein kinase IV (CaMK IV), mitogen-activated protein kinase (MAPK), and cAMP response element-binding protein (CREB) were found to play important roles in the ES-induced BDNF release from SCs. In conclusion, ES is capable of activating SCs to secrete BDNF, which requires the involvement of calcium influx through T-type VGCC and calcium mobilization from internal calcium stores. In addition, activation of CaMK IV, MAPK, and CREB were also involved in the ES-induced BDNF release. The findings indicate that ES can improve the neurotrophic ability in SCs and raise the possibility of developing electrically stimulated SCs as a source of cell therapy for nerve injury in both peripheral and central nervous systems.

Ephedrine hydrochloride inhibits PGN-induced inflammatory responses by promoting IL-10 production and decreasing proinflammatory cytokine secretion via the PI3K/Akt/GSK3ß pathway.

Approaches for controlling inflammatory responses and reducing the mortality rate of septic patients remain clinically ineffective; new drugs need to be identified that can induce anti-inflammatory responses. Ephedrine hydrochloride (EH) is a compound that is widely used in cardiovascular diseases, especially to treat hypotension caused by either anesthesia or overdose of antihypertensive drugs. In this study, we reported that EH also plays an important role in the control of the inflammatory response. EH increased IL-10 and decreased proinflammatory cytokine (IL-6, tumor-necrosis factor (TNF)-α, IL-12 and IL-1ß) expression in primary peritoneal macrophages and Raw264.7 cells treated with peptidoglycan (PGN), a Gram-positive cell wall component. The anti-inflammatory role of EH was also demonstrated in an experimental mouse model of peritonitis induced by intraperitoneal PGN injection. The phosphatidylinositol 3-kinase (PI3K)/Akt pathway was found to be responsible for the EH-mediated increase in IL-10 production and decrease in IL-6 expression. Therefore, our results illustrated that EH can help maintain immune equilibrium and diminish host damage by balancing the production of pro- and anti-inflammatory cytokines after PGN challenge. EH may be a new potential anti-inflammatory drug that can be useful for treating severe invasive Gram-positive bacterial infection.

Risk factors for postoperative recurrence of cardiac myxoma and the clinical managements: a report of 5 cases in one center and review of literature.

BACKGROUND: Recurrence or metastasis of myxomas is not rare and can lead to malignancy. We aimed to analyze the risk factors for postoperative cardiac myxoma recurrence and to summarize its clinical characteristics, treatments and classification. METHODS: The clinical data of 5 patients with recurrent cardiac myxoma were retrospectively analyzed and our clinical experience was summarized. Moreover, the relevant literatures were reviewed. RESULTS: All the five cases of primary myxomas were derived from atypical positions. One patient had early distant metastasis, one had family history, and two suffered malignant recurrence. The recurrence interval was (2.30 ± 2.16) years and the recurrent tumors were all found in different chambers from those of the corresponding primary tumors. Re-operation was performed after recurrence. One patient died of heart failure after malignant recurrence, and the other 4 cases had satisfactory therapeutic outcomes after re-operations. Our experience advocated a clinical classification of "typical" and "atypical" cardiac myxoma, the typical myxomas referred to the tumors locating at the left atria, with single pedicle, rooted at or around the fossa ovalis, involving no genetic causes, and the atypical myxomas included the familial tumors, tumors stemming from multiple chambers, rooted in abnormal positions of the left atrium, with evident genetic mutation, or with malignant tendency. CONCLUSIONS: Postoperative follow-up is of vital importance for patients with myxomas characterized by multi-chamber distribution, early distant metastasis, atypical origin, and family history. Once recurs, re-operation is necessary and should be performed immediately.