MiR-497-5p ameliorates the oxyhemoglobin-induced subarachnoid hemorrhage injury in vitro by targeting orthodenticle homeobox protein 1 (Otx1) to activate the Nrf2/HO-1 pathway.

Subarachnoid hemorrhage (SAH) is a neurological disorder that severely damages the brain and causes cognitive impairment. MicroRNAs are critical regulators in a variety of neurological diseases. MiR-497-5p has been found to be downregulated in the aneurysm vessel walls obtained from patients with aneurysmal subarachnoid hemorrhage, but its functions and mechanisms in SAH have not been reported. Therefore, this study was designed to investigate the effect of miR-497-5p and its related mechanisms in SAH. We established an in vitro SAH model by exposing PC12 cells to oxyhemoglobin (oxyHb). We found that miR-497-5p was downregulated in SAH serum and oxyHb-treated PC12 cells, and its overexpression inhibited the oxyHb-induced apoptosis, inflammatory response and oxidative stress via activation of the Nrf2 pathway. Mechanistically, the targeting relationship between miR-497-5p and Otx1 was verified by luciferase reporter assays. Moreover, Otx1 upregulation abolished the protective effects of miR-497-5p upregulation against oxyHb-induced apoptosis, inflammation and oxidative stress in PC12 cells. Collectively, our findings indicate that miR-497-5p could inhibit the oxyHb-induced SAH damage by targeting Otx1 to activate the Nrf2/HO-1 pathway, which provides a potential therapeutic target for SAH treatment.

Effects of rehabilitation therapy based on exercise prescription on motor function and complications after hip fracture surgery in elderly patients.

BACKGROUND: Exercise rehabilitation training is an important measure for improving the prognosis of patients with hip fractures. However, the particular program that works effectively and the efficiency of exercise therapy are still controversial. OBJECTIVE: To compare the effects of usual postoperative care combined with rehabilitation based on exercise prescription on motor function and complications in elderly patients who underwent surgery for hip fracture. METHODS: This was an observational study. A total of 71 elderly patients with hip fractures who were treated with hip arthroplasty and internal fixation of the proximal femur with an intramedullary nail at Suzhou Municipal Hospital from October 2020 to December 2021 were included; 11 cases were excluded (eight cases were excluded due to loss of follow-up, two due to deaths from other causes, and one due to other reasons). Finally, 60 patients (18 males and 42 females) were included. Patients were randomly assigned to the control (n = 30) and experimental (n = 30) groups using a random number generator. Patients in the control group received usual postoperative care, whereas those in the experimental group received usual postoperative care combined with rehabilitation training based on the principles of exercise prescription. We recorded the motor function (Harris hip score), daily living ability (Barthel Index), and complications at discharge and 1, 3, and 6 months postoperatively for statistical analysis. RESULTS: The Harris hip score and Barthel Index score were significantly higher at 1, 3, and 6 months postoperatively than at discharge in both groups (p < 0.05). The Harris hip score and Barthel Index score at discharge and 1, 3, and 6 months postoperatively were significantly higher in the experimental group than in the control group (p < 0.05). The incidence of complications at 6 months postoperatively was significantly lower in the experimental group than in the control group (13% vs. 37%). CONCLUSIONS: Rehabilitation therapy based on exercise prescription helps improve hip function and the ability to perform activities of daily living and related postoperative complications after hip fracture surgery in elderly patients. The findings of our study will guide decision-making in clinical practice and improve the clinical management of hip fractures in elderly patients postoperatively.

ACE2 Rescues Impaired Autophagic Flux Through the PI3K/AKT Pathway After Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is one of the life-threatening neurosurgical diseases in central nervous system. Autophagy has been previously demonstrated to exert vital roles in SAH development. Angiotensin I converting enzyme 2 (ACE2) has been revealed as a regulator of autophagy in neurosurgical diseases. However, effect of ACE2 on autophagy in SAH progression has not been clarified. First, we explored the relationship between autophagy and SAH progression by establishing a mouse model of SAH under the administration of 3-MA (the autophagy inhibitor). Next, we examined ACE2 expression in the cerebral cortex of SAH mice ex vivo with RT-qPCR. Subsequently, we assessed the biological function of ACE2 on brain injury, the autophagic flux pathway and the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling ex vivo via neurological scoring, TUNEL assay, western blot analysis and immunofluorescence staining assay. Finally, we carried out rescue assays under chloroquine (CQ, the autophagic flux inhibitor) and LY294002 (the PI3K/AKT signaling inhibitor) administration. 3-MA mitigated brain injury after SAH, and ACE2 was downregulated in cerebral cortex of SAH mice. Moreover, ACE2 elevation alleviated cell apoptosis, cerebral edema, and neurological deficits, ameliorated the autophagic flux pathway and activated the PI3K/AKT signaling in SAH mice. Furthermore, CQ and LY294002 neutralized the effects of overexpressed ACE2 on neuronal apoptosis, cerebral edema, and neurological deficits in SAH mice. Overall, ACE2 lessened neuronal injury via the autophagic flux and PI3K/AKT pathways. This research might provide a potential novel direction for clinical treatment of SAH.

Regenerating and repairing degenerative intervertebral discs by regulating the micro/nano environment of degenerative bony endplates based on low-tension mechanics.

BACKGROUND: Conservative treatment is the recommended first-line treatment for degenerative disc diseases. Traction therapy has historically been one of the most common clinical methods to address this, but the clinical effect remains controversial. METHODS: Forty-two six-month-old male Sprague-Dawley rats were randomly divided into six groups: the model group (Group A, four coccyx vertebrae (Co7-Co10) were fixed with customized external fixators, and the vertebral disc degeneration model was constructed by axial compression of the target segment Co8 - Co9 for 4 weeks), the experimental control group (Group B, after successful modeling, the external fixation device was removed and self-rehabilitation was performed) and four intervention groups (Groups C to F): Groups C and E: Co8 - Co9 vertebrae compressed for 4 weeks followed by two or 4 weeks of high tension traction (HTT), respectively, and Groups D and F: vertebrae compressed for 4 weeks followed by two or 4 weeks of low-tension traction (LTT), respectively. Imaging tests (X-ray and MRI) were performed to assess disc height and T2 signal intensity at each time point. After the experiment, the animals were euthanized, and the caudal vertebrae were collected for analysis of intervertebral disc histopathology, proteoglycan content, and micronanostructure of the annulus fibrosus, nucleus pulposus and bony endplate. RESULTS: Signs of tissue regeneration were apparent in all four intervention groups. After two to 4 weeks of intervention (HTT and LTT), the morphology of pores in the bony endplate, their number, and diameter had recovered significantly compared with those in Group A. The LTT group was superior to the HTT group, and the 4w in situ group was significantly superior to the 2w group. Meanwhile, the histological scores of discs, the mean fibril diameter and modulus of annulus fibrosus were significantly improved compared with the control groups, and the LTT group was superior to HTT group. CONCLUSIONS: Low-tension traction better promotes active reconstruction of bony endplates and improves the elastic modulus and micro/nanostructure of the disc. Thus, it further promotes the regeneration and repair of intervertebral discs.

Characteristics, treatments, and prognosis of a critical illness polyneuromyopathy patient with positive anti-GM1 after severe traumatic brain injury: A case report.

To investigate the clinical features, treatment and prognosis of critical illness polyneuromyopathy (CIPNM) in patients with severe traumatic brain injury (sTBI) who had positive anti-ganglioside GM1 (anti-GM1) antibody IgG. A case of CIPNM with positive anti-GM1 antibody IgG was retrospectively analysed and followed-up for 30 months. After 1 week of treatment with large dose of short-term glucocorticoid and human immunoglobulin, the muscle strength of both lower extremities was restored to grade 1. Three months later, the muscle strength and muscle tension of the patient's limbs returned to normal except for grade 3 of bilateral dorsal extensor muscle strength. In addition, the patient can walk alone with a waddling gait. After 30 months, there was no recurrence. The application of large dose of short-term glucocorticoid and human immunoglobulin to CIPNM that are positive for anti-GM1 antibodies may be an effective treatment.

Structure and mechanical properties of high-weight-bearing and low-weight-bearing areas of hip cartilage at the micro- and nano-levels.

BACKGROUND: Articular cartilage has a high-weight-bearing area and a low-weight-bearing area, the macroscopic elastic moduli of the two regions are different. Chondrocytes are affected by the applied force at the microscopic level. Currently, the modulus of the two areas at the micro and nano levels is unknown, and studies on the relationship between macro-, micro- and nano-scale elastic moduli are limited. Such information may be important for further understanding of cartilage mechanics. Moreover, the surface morphology, proteoglycan content, and micro and nano structure of the two areas, which influences the mechanical properties of cartilage should be discussed. METHODS: Safranin-O/Fast Green staining was used to evaluate the surface morphology and semi-quantify proteoglycan content of porcine femoral head cartilage between the two weight-bearing areas. The unconfined compression test was used to determine the macro elastic modulus. Atomic force microscope was used to measure the micro and nano compressive elastic modulus as well as the nano structure. Scanning electron microscope was employed to evaluate the micro structure. RESULTS: No significant differences in the fibrillation index were observed between two areas (P = 0.5512). The Safranin-O index of the high-weight-bearing area was significantly higher than that of the low-weight-bearing area (P = 0.0387). The compressive elastic modulus of the high-weight-bearing area at the macro and micro level was significantly higher than that of the low-weight-bearing area (P = 0.0411 for macro-scale, and P = 0.0001 for micro-scale), while no statistically significant differences were observed in the elastic modulus of collagen fibrils at the nano level (P = 0.8544). The density of the collagen fibers was significantly lower in the high-weight-bearing area (P = 0.0177). No significant differences were observed in the structure and diameter of the collagen fibers between the two areas (P = 0.7361). CONCLUSIONS: A higher proteoglycan content correlated with a higher compressive elastic modulus of the high-weight-bearing area at the micro level than that of the low-weight-bearing area, which was consistent with the trend observed from the macroscopic compressive elastic modulus. The weight-bearing level was not associated with the elastic modulus of individual collagen fibers and the diameter at the nano level. The micro structure of cartilage may influence the macro- and micro-scale elastic modulus.

Knockdown of long non-coding RNA NEAT1 inhibits glioma cell migration and invasion via modulation of SOX2 targeted by miR-132.

BACKGROUND: A better understanding of the molecular mechanism involving lncRNA-miRNA-mRNA network underlying glioma genesis is beneficial to the treatment of glioma. This study was designed to investigate the role of lncRNA NEAT1, miR-132 and SOX2 interaction in glioma. METHODS: Microarray analysis was conducted to identify the differentially expressed lncRNAs in glioma tissues. The expression levels of NEAT1, miR-132 and SOX2 were determined by qRT-PCR and western blot. Proliferation of glioma cells was detected by MTT assay, while migration and invasion were determined by transwell assay. The target relationships were predicted by miRcode algorithm, and confirmed by dual luciferase reporter gene assay. RESULTS: NEAT1 was up-regulated in glioma. Knockdown of NEAT1 inhibited glioma cells' viability, migration and invasion. MiR-132 was down-regulated while SOX2 was up-regulated in glioma cells. NEAT1 negatively regulated the expression of miR-132 in glioma while miR-132 targeted SOX2 to down-regulate its expression. CONCLUSION: NEAT1 promoted glioma development by promoting SOX2 expression through suppressing miR-132.

Intervertebral disc degeneration induced by long-segment in-situ immobilization: a macro, micro, and nanoscale analysis.

BACKGROUND: Cervical spine fixation or immobilization has become a routine treatment for spinal fracture, dislocation, subluxation injuries, or spondylosis. The effects of immobilization of intervertebral discs of the cervical spine is unclear. The goal of this study was to evaluate the effects of long-segment in-situ immobilization of intervertebral discs of the caudal vertebra, thereby simulating human cervical spine immobilization. METHODS: Thirty-five fully grown, male Sprague-Dawley rats were used. Rats were randomly assigned to one of five groups: Group A, which served as controls, and Groups B, C, D, and E, in which the caudal vertebrae were in-situ immobilized using a custom-made external device that fixed four caudal vertebrae (Co7-Co10). After 2 weeks, 4 weeks, 6 weeks, and 8 weeks of in-situ immobilization, the caudal vertebrae were harvested, and the disc height, the T2 signal intensity of the discs, disc morphology, the gene expression of discs, and the structure and the elastic modulus of discs was measured. RESULTS: The intervertebral disc height progressively decreased, starting at the 6th week. At week 6 and week 8, disc degeneration was classified as grade III, according to the modified Pfirrmann grading system criteria. Long-segment immobilization altered the gene expression of discs. The nucleus pulposus showed a typical cell cluster phenomenon over time. The annulus fibrosus inner layer began to appear disordered with fissure formation. The elastic modulus of collagen fibrils within the nucleus pulposus was significantly decreased in rats in group E compared to rats in group A (p < 0.05). On the contrary, the elastic modulus within the annulus was significantly increased in rats in group E compared to rats in group A (p < 0.05). CONCLUSION: Long-segment in-situ immobilization caused target disc degeneration, and positively correlated with fixation time. The degeneration was not only associated with changes at the macroscale and microscale, but also indicated changes in collagen fibrils at the nanoscale. Long-segment immobilization of the spine (cervical spine) does not seem to be an innocuous strategy for the treatment of spine-related diseases and may be a predisposing factor in the development of the symptomatic spine.

Effects of hemoglobin level on the early postsurgical cerebral metabolism in patients with severe traumatic brain injury.

OBJECTIVE: The study aims to explore the effects of different levels of haemoglobin (Hb) on early cerebral metabolism in patients with postoperative severe traumatic brain injury (TBI) . METHOD: Fifty-nine patients were randomly divided into catheter oxygen group and ventilator-assisted respiratory group. Each group was subsequently divided into three subgroups basing on different Hb level: Hb ≤ 70 g/L subgroup, 71 g/L ≤ Hb≤90 g/L subgroup and Hb ≥ 91 g/L subgroup. The blood samples from the femoral artery and the affected side internal jugular vein were, respectively, taken at the same time from the patient after postoperative 3 days. RESULTS: The incidence of anaemia after severe TBI operation was 88.14%. The VADL and cerebral glucose uptake (CMRglu) in both Hb ≤ 70 g/L and 71 g/L ≤ Hb≤90 g/L patients of oxygen catheter group were less than that in Hb ≥ 91 g/L patients. In the ventilator-assisted breathing group, the VADL and CMRglu of 71 g/L ≤ Hb≤90 g/L patients and Hb ≥ 91 g/L patients were lower than those in Hb ≤ 70 g/L patients. The result from comparing the two 71 g/L ≤ Hb ≤ 90 g/L subgroups showed that the brain metabolic indexs in the ventilator-assisted breathing group were better than those in the catheter oxygen group. CONCLUSIONS: In severe TBI postoperative patients, Hb≤90 g/L induced decrease in aerobic oxidation in brain tissue. Moreover, for the same Hb level of 71 g/L ≤ Hb≤90 g/L, ventilator-assisted breathing significantly improved cerebral metabolism.

Preparation and application of collagen scaffold-encapsulated silver nanoparticles and bone morphogenetic protein 2 for enhancing the repair of infected bone.

The healing of contaminated/infected bone defects is a significant clinical challenge. Here, a novel collagen scaffold composite encapsulating silver nanoparticles (AgNP) and bone morphogenetic protein 2 (BMP-2) was prepared to enhance the healing of infected bone defects. Collagen scaffolds conjugated with AgNP possessed strong antibacterial properties that were dependent on the release rate of Ag(+). After introducing BMP-2, the BMP-2/AgNP/collagen scaffold composites did not adversely affect the adherence or proliferation of bone marrow-derived mesenchymal stromal cells (BMSCs). Differentiation of BMSCs toward osteoblasts was induced by the upregulation of RUNX2, osteopontin and osteonectin expression. BMP-2/AgNP/collagen scaffold composites, therefore, possess the antibacterial activity of AgNP and the osteoinductivity of BMP-2, making these composites an ideal pharmaceutical for the regeneration of bone in infected wounds.

Insights into the mechanical microenvironment within the cartilaginous endplate: An emerging role in maintaining disc homeostasis and normal function.

Biomechanical factors are strongly linked with the emergence and development of intervertebral disc degeneration (IVDD). The intervertebral disc (IVD), as a unique enclosed biomechanical structure, exhibits distinct mechanical properties within its substructures. Damage to the mechanical performance of any substructure can disrupt the overall mechanical function of the IVD. Endplate degeneration serves as a significant precursor to IVDD. The endplate (EP) structure, especially the cartilaginous endplate (CEP), serves as a conduit for nutrient and metabolite transport in the IVD. It is inevitably influenced by its nutritional environment, mechanical loading, cytokines and extracellular components. Currently, reports on strategies targeting the CEP for the prevention and treatment of IVDD are scarce. This is due to two primary reasons: first, limited knowledge of the biomechanical microenvironment surrounding the degenerated CEP cells; and second, innovative biological treatment strategies, such as implanting active cells (disc or mesenchymal stem cells) or modulating natural cell activity through the addition of therapeutic factors or genes to treat IVDD often overlook a critical aspect-the restoration of the nutrient supply function and mechanical microenvironment of the endplate. Therefore, restoring the healthy structure of the CEP and maintaining a stable mechanical microenvironment within the EP are crucial for the prevention of IVDD and the repair of degenerated IVDs. We present a comprehensive literature review on the mechanical microenvironment characteristics of cartilage endplates and their associated mechanical signaling pathways. Our aim is to provide valuable insights into the development and implementation of strategies to prevent IVDD by delaying or reversing CEP degeneration.

Global, regional, national trends of femur fracture and machine learning prediction: Comprehensive findings and questions from global burden of disease 1990-2019.

Background: Femur fracture is a type of fracture with high disability and mortality. There is no comprehensive analysis and prediction of the global distribution of femur fractures, so we conducted this study. Methods: Age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), and years living with disability (YLDs) of femur fractures (excluding femoral neck) were downloaded from the Global burden of disease database. Trend analysis was performed, and 6 time-series machine learning algorithms were applied to predict the global ASIR, ASPR, and YLDs. Results: ASPR for femur fracture had been increasing in most countries worldwide from 1990 to 2019, with the highest in East Asia (AAPC = 1.25 95%Confidence Interval (1.2, 1.3)) and lowest in Central Latin America (AAPC = -0.74 95%CI (-0.81, -0.67)). However, ASIR showed a significant downward trend worldwide, with East Saharan Africa decreasing the most (AAPC = -4.04 95%CI (-5.56, -2.47)), and East Asia elevating the most (AAPC = 1.11 95%CI (0.87, 1.42)). YLDs were increasing over the world, with East Asia still elevating the most AAPC= (3.9 95%CI (3.85, 3.95)), with the only region of decrease being Eastern Europe (AAPC = -0.28 95%CI (-0.3, -0.26)). Both ASPR and ASIR were higher in women than in men in the >75 year group, whereas YLDs was lower in women than in men in the >60 year group. Globally, the ARIMA model was optimal in the prediction of ASPR, the PROPHET model effected in the prediction of ASIR, and the PROPHET WITH XGBOOST model was the best in the prediction of YLDs. The projections showed increase in both ASPR and YLDs, except for ASIR decreasing by 2030. Conclusions: Our study found a rise in femur fracture ASPR and ASIR from 1990 to 2019 in war conflict areas and East Asia, meanwhile, the YLDs of femur fracture increased in populous countries. In both 1990 and 2019, both ASPR and ASIR were higher in women over 75 years than that in men, but YLDs was higher in men over 60 years than that in women. In 2020-2030, while global femur fracture ASIR might decline, both ASPR and YLDs might rise. The Translational Potential of this article: Femur fracture is a high-energy injury due to direct violence, and in war, conflicting and underdeveloped regions such as East Asia. Accidental injuries may occur due to the rapid development of industry and the frequent traffic accidents. This study suggests that we should focus on elderly women (≥75 years) in the above regions in the future. For older men (>60 years old), more attention should be paid to post-fracture functional rehabilitation and early reintegration into society to reduce the disability rate and lower the socio-economic burden.

Suppression of MALAT1 alleviates neurocyte apoptosis and reactive oxygen species production through the miR-499-5p/SOX6 axis in subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH), a common devastating cerebrovascular accident, is a great threat to human health and life. Exploration of the potential therapeutic target of SAH is urgently needed. Previous studies showed that long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) promotes cell apoptosis in various diseases, while its role in SAH remains unclear. In our study, we established a mouse model of SAH and used the oxyhemoglobin (OxyHb) to induce neuronal injury in vitro. Interestingly, MALAT1 was found upregulated in brain tissues of SAH mice and OxyHb-stimulated neurons. In addition, knockdown of MALAT1 attenuated apoptosis and decreased reactive oxygen species (ROS) production in OxyHb-stimulated neurons. Mechanistically, we demonstrated that MALAT1 bound with miR-499-5p. Furthermore, our findings indicated that miR-499-5p bound to SOX6 3' untranslated region (UTR) and negatively regulated SOX6 mRNA and protein levels. Rescue assays suggested that SOX6 overexpression counteracted the effects of MALAT1 knockdown on neurocyte apoptosis, and ROS production in OxyHb-stimulated neurons. The in vivo assays indicated that knockdown of MALAT1 improved brain injury of SAH mice. Our study demonstrates that silencing of MALAT1 alleviates neurocyte apoptosis and reduces ROS production through the miR-499-5p/SOX6 axis after SAH injury.

[Related factors of early post-operative prognosis of meningiomas: an analysis of 953 surgical cases].

OBJECTIVE: To study the related factors of early post-operative prognosis of meningiomas. METHODS: The clinical data of 953 patients with meningiomas were recorded and statistically analyzed with χ(2) test of single factor and logistic regression model of multivariate factors. Patient age; tumor size; tumor location; pre-operative complication of patients such as hypertension, diabetes, heart disease and cerebral infarction; the extent of tumor resection; hemorrhagic shock; blood loss or hemorrhagic shock and brain swelling intra-operatively were taken as variables. The prognosis was evaluated by postoperative Karnofsky performance scale. RESULTS: The prognosis was significantly correlated with the patient age, tumor size, tumor location, preoperative cerebral infarction, the extent of tumor resection, blood loss and hemorrhagic shock intra-operatively (P < 0.05). Such factors as tumor size, preoperative cerebral infarction, the extent of tumor resection (Simpson's scale) and intra-operative hemorrhagic shock were independent risk factors of prognosis for meningiomas. Other factors, such as hypertension, diabetes and heart disease, were unrelated with the prognosis of meningiomas (P > 0.05). CONCLUSION: Patient age, tumor location and pre-operative complications of patients maybe affect the early postoperative prognosis of meningiomas. But such factors as tumor size, preoperative cerebral infarction, the extent of tumor resection and intra-operative hemorrhagic shock are independent risk factors for the post-operative prognosis of meningiomas.

Baicalin suppresses autophagy-dependent ferroptosis in early brain injury after subarachnoid hemorrhage.

Early brain injury, characterized by massive cell apoptosis or death, is identified as a critical pathophysiological process during subarachnoid hemorrhage (SAH). Ferroptosis, a class of autophagy-dependent cell death discovered in 2012, is induced by iron-dependent lipid peroxidation accumulation. The present study was designed to study the role of baicalin in autophagy-dependent ferroptosis in early brain injury after SAH. Neurological scores and brain water content were measured to evaluate brain injury. Measurement of iron ion, malondialdehyde (MDA), lipid reactive oxygen species was conducted for ferroptosis evaluation. Immunofluorescence staining, western blotting, and flow cytometry analysis were used to evaluate autophagy and apoptosis. First, we observed that, compared with sham rats, SAH rats had lower neurobehavioral scores. Next, baicalin was proven to decrease the Fe2+, malondialdehyde, and ROS levels in the brain tissues of rats. Also, baicalin was confirmed to suppress the beclin1, LC3-II, and LC3-I protein levels in rat brain tissues. Moreover, we found that baicalin inhibited neuronal apoptosis. Finally, the effects of baicalin on brain injury in the SAH rats were verified. Overall, our results demonstrated that baicalin suppressed autophagy-dependent ferroptosis in EBI after SAH.

Low energy extracorporeal shock wave therapy combined with low tension traction can better reshape the microenvironment in degenerated intervertebral disc regeneration and repair.

BACKGROUND: Low-tension traction is more effective than high-tension traction in restoring the height and rehydration of a degenerated disc and to some extent the bony endplate. This might better reshape the microenvironment for disc regeneration and repair. However, the repair of the combination of endplate sclerosis, osteophyte formation, and even collapse leading to partial or nearly complete occlusion of the nutrient channel is greatly limited. PURPOSE: To evaluate the effectiveness of low-intensity extracorporeal shock wave therapy (ESWT) combined with low tension traction for regeneration and repair of moderately and severely degenerated discs; to explore the possible mechanism of action. STUDY DESIGN: Animal study of a rat model of degenerated discs. METHODS: A total of thirty-five 6-month old male Sprague-Dawley rats were randomly assigned to one of five groups (n=7, each group). In Group A (model group), caudal vertebrae were immobilized using a custom-made external device to fix four caudal vertebrae (Co7-Co10) whereas Co8-Co9 underwent 4 weeks of compression to induce moderate disc degeneration. In Group B (experimental control group), as in Group A, disc degeneration was successfully induced after which the fixed device was removed for 8 weeks of self-recovery. The remaining three groups of rats represented the intervention Groups (C-E): after successful generation of disc degeneration in Group C (com - 4w/tra - 4w) and Group D (com - 4w/ESWT), as described for group A, low-tension traction (in-situ traction) or low-energy ESWT was administered for 4 weeks (ESWT parameters: intensity: 0.15 Mpa; frequency: 1 Hz; impact: 1,000 each time; once/week, 4 times in total); Group E (com - 4w/tra - 4w/ESWT): disc degeneration as described for group A, low-tension traction combined with low-energy ESWT was conducted (ESWT parameters as Group D). After experimentation, caudal vertebrae were harvested and disc height, T2 signal intensity, disc morphology, total glycosaminoglycan (GAG) content, gene expression, structure of the Co8-Co9 bony endplates and elastic moduli of the discs were measured. RESULTS: After continuous low-tension traction, low energy ESWT intervention or combined intervention, the degenerated discs effectively recovered their height and became rehydrated. However, the response in Group D was weaker than in the other intervention groups in terms of restoration of intervertebral disc (IVD) height, whereas Group E was superior in disc rehydration. Tissue regeneration was evident in Groups C to E using different interventions. No apparent tissue regeneration was observed in the experimental control group (Group B). The histological scores of the three intervention groups (Groups C-E) were lower than those of Groups A or B (p<.0001), and the scores of Groups C and E were significantly lower than those of Group D (p<.05), but not Group C versus Group E (p>.05). Compared with the intervention groups (Groups C-E), total GAG content of the nucleus pulposus (NP) in Group B did not increase significantly (p>.05). There was also no significant difference in the total GAG content between Groups A and B (p>.05). Of the three intervention groups, the recovery of NP GAG content was greatest in Group E. The expression of collagen I and II, and aggrecan in the annulus fibrosus (AF) was up-regulated (p<.05), whereas the expression of MMP-3, MMP-13, and ADAMTS-4 was down-regulated (p<.05). Of the groups, Group E displayed the greatest degree of regulation. The trend in regulation of gene expression in the NP was essentially consistent with that of the AF, of which Group E was the greatest. In the intervention groups (Groups C-E), compared with Group A, the pore structure of the bony endplate displayed clear changes. The number of pores in the endplate in Groups C to E was significantly higher than in Group A (p<.0001), among which Group C versus Group D (p=.9724), and Group C versus Group E (p=.0116). There was no significant difference between Groups A and B (p=.5261). In addition, the pore diameter also increased, the trend essentially the same as that of pore density. There was no significant difference between the three intervention groups (p=.7213). It is worth noting that, compared with Groups A and B, peripheral pore density and size in Groups D and E of the three intervention groups recovered significantly. The elastic modulus and diameter of collagen fibers in the AF and NP varied with the type of intervention. Low tension traction combined with ESWT resulted in the greatest impact on the diameter and modulus of collagen fibers. CONCLUSIONS: Low energy ESWT combined with low tension traction provided a more stable intervertebral environment for the regeneration and repair of moderate and severe degenerative discs. Low energy ESWT promoted the regeneration of disc matrix by reducing MMP-3, MMP-13, and ADAMTS-4 resulting in inhibition of collagen degradation. Although axial traction promoted the recovery of height and rehydration of the IVD, combined with low energy ESWT, the micro-nano structure of the bony endplate underwent positive reconstruction, tension in the annulus of the AF and nuclear stress of the NP declined, and the biomechanical microenvironment required for IVD regeneration and repair was reshaped.

Microanatomy of the lumbar vertebral bony endplate of rats using scanning electron microscopy.

INTRODUCTION: The bony endplate of a vertebra is a porous structure containing a large number of capillaries. To date, not very much is known regarding the appearance of the bony endplate microstructure, or the distribution of foramina in the bony endplate. HYPOTHESIS: The purpose of this study was to provide information on this microstructure based on scanning electron microscopy (SEM) images. MATERIALS AND METHODS: The bony endplates of rats was observed by SEM scanning. The resulting SEM images were used to evaluate the structural characteristics of the bony endplates, such as the shape and the foramen distribution. Quantitative data were analyzed using SPSS software. RESULTS: A bony endplate resembled a concave lens and had a unique three-dimensional structure with a large number of surface and interior foramina. The anterior side of the bony endplate had a large number of heterogeneous foramina. The majority of the foramina were seen concentrated toward the center of the bony endplate, as the density decreased further away from the center with few foramina at the margins. The posterior side of the bony endplate had numerous, larger, and more evenly distributed foramina. The integral structure resembled a sponge, and most of the foramina contained capillary structures. DISCUSSION: The spongy structure of the bony endplate is the structural basis of nutrient transport. Depending on the location of the bony endplate, capillaries can penetrate it and contact to the cartilage endplate, thus supporting nutritional transport. The findings provide a theoretical basis for future studies on intervertebral disc degeneration.

Stable mechanical environments created by a low-tension traction device is beneficial for the regeneration and repair of degenerated intervertebral discs.

BACKGROUND: By blocking the cascade of reactions leading to intervertebral disc degeneration through immobilization-traction, a delay in intervertebral disc degeneration and its regeneration, to some extent, has been observed. However, the precise balance of regulation of the microenvironment of intervertebral disc biomechanics and coordination of the complex spatiotemporal reconstruction of the extracellular matrix have not yet been solved, and clinical results are far from successful. PURPOSE: In the present study, a mechanical degeneration model was constructed to evaluate the possibility and effectiveness of disc regeneration or repair through low-tension traction of degenerated discs so as to provide basic biomechanical information for clinical optimization of the traction device and to establish traction parameters for prevention and treatment of disc degeneration. STUDY DESIGN: A macro-, micro-, and nano-level structural analysis of degenerative discs of rat tail before and after controlled traction. METHODS: Six-month-old male Sprague-Dawley rats were randomly divided into seven groups: Group A: control group (instrumented with Kirschner [K]-wires only); Group B: Model group (caudal vertebrae immobilized using a custom-made external device to fix four caudal vertebrae [Co7-Co10], while Co8-Co9 vertebrae underwent 4 weeks of compression to induce disc degeneration); Group C: experimental control group (devices removed after the 4 week compression described in Group B, and recovered by themselves for 4 weeks). The remaining four groups represented intervention groups (Groups D and F: Co8-Co9 vertebrae compressed for 4 weeks followed by 2 or 4 weeks of in situ traction, respectively; Groups E and G: vertebrae compressed for 4 weeks followed by 2 or 4 weeks of excessive traction, respectively). X-ray and magnetic resonance imaging were performed at each time point to measure disc height and T2 signal intensity. At the end of the experiment, the animals were euthanized and tail vertebrae harvested for analysis of intervertebral disc histopathology, proteoglycan content, elastic modulus of fibers of the annulus fibrosus (AF) and nucleus pulposus (NP), and microstructure of the bony end plate. RESULTS: After 2 to 4 weeks of continuous traction (in situ and excessive traction), the Co8-Co9 intervertebral disc space of rats in Groups D to G increased significantly compared with Groups B and C (p < .05). In addition, signs of tissue regeneration were apparent in all four intervention groups (D-G). In addition, histologic scores of the intervention groups (D-G) were significantly lower than those in the model and experimental control groups (Groups B and C, respectively), although no significant difference was found between those four groups. Compared with the model group (Group B), total proteoglycan content of the NP in the intervention groups (D-G) increased significantly (p < .05). After 2 to 4 weeks of intervention (in situ and excessive traction), the morphology of pores in the bony end plate, their number, and the diameter had recovered significantly compared with those in Group B. The in situ traction group was superior to the excessive traction group, and 4 weeks in situ group significantly superior to the 2 weeks group. In all intervention groups, in both the inner and outer AF, mean fibril diameter decreased significantly (p < .05), although they remained larger in the excessive traction group than that in the in situ traction group. Consistent with trend in collagen fiber diameter, the outer AF was stiffer than the inner, and the modulus of the AF in each intervention group not significantly different from that of the control group (Group A) except Group C. However, within the NP, the variation in trend in diameter and modulus of collagen fibers was essentially inconsistent with that of the AF. CONCLUSIONS: Degenerated discs exhibit greater reconstruction after low tension traction. It is clear that the intervertebral disc mechanical microenvironment depends to a greater extent on low-tension traction than high-tension traction.

Early degeneration of the meniscus revealed by microbiomechanical alteration in a rabbit anterior cruciate ligament transection model.

BACKGROUND: The microbiomechanical properties of the meniscus influence the cell response to the surrounding biomechanical environment â€‹and are beneficial to understand meniscus repairing and healing. To date, however, this information remains ambiguous. This study aims to characterise the microbiomechanical properties of the meniscus after degeneration in a rabbit anterior cruciate ligament transection (ACLT) model and to analyse the corresponding histology at the macroscale and chemical composition. METHODS: Twenty New Zealand white rabbits were used. Menisci were collected from the knee joints 4 and 8 weeks after the ACLT and from those of the corresponding control groups. The central portions of both medial and lateral menisci were investigated using atomic force microscopy, histological study, and an energy-dispersive spectrometer. The evaluation was conducted regionally within the inner, middle, and outer sites from the top layer (facing the femoral surface) to the bottom layer (facing the tibial surface) in both the lateral and medial menisci to obtain the site-dependent properties. RESULTS: At 4 weeks after surgery, the dynamic elastic modulus at the microlevel increased significantly at both the top and bottom layers compared with the intact meniscus (P â€‹= â€‹0.021). At 8 weeks after surgery, the stiffening occurred in all regions (P â€‹= â€‹0.030). The medial meniscus showed greater change than the lateral meniscus. All these microbiomechanical alterations occurred before the histological findings at the macroscale. CONCLUSION: The microbiomechanical properties in the meniscus changed significantly after ACLT and were site dependent. Their alterations occurred before the histological changes of degeneration were observed. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The results of our study indicated that degeneration promoted meniscus stiffening. Thus, they provide a better understanding of the disease process affecting the meniscus. Our results might be beneficial to understand how mechanical forces distribute throughout the healthy and pathologic joint. They indicate the possibility of early diagnosis using a minimally invasive arthroscopic tool, as well as they might guide treatment to the healthy and pathologic meniscus and joint.

Treatment of a giant complicated distal posterior inferior cerebellar artery aneurysm: A case report and literature review.

Giant intracranial aneurysms, especially giant aneurysms of the distal posterior inferior cerebellar artery (PICA), remain the most difficult and challenging cerebrovascular lesions for neurosurgeons to treat. The morbidity and mortality rates of microsurgical clipping are relatively high, and endovascular embolization is also associated with many complications. In the present report, the case of a 46-year-old female patient who presented with headache and dizziness for 3 years, which was aggravated and combined with limb weakness for 1 day, is presented. A CT scan showed a lesion occupying the fourth ventricle, with slight bleeding. A MR scan also revealed a lesion occupying the fourth ventricle and compressing the brainstem, and there was distortion of the cisterns around the brainstem. CT angiography examination showed a giant irregular aneurysm located in the PICA. After evaluation, the PICA aneurysm was removed, and the PICA was clipped via a microsurgical technique without ischemia or neurological sequelae. Long-term follow-up demonstrated that the symptoms of headache and dizziness disappeared without relapse. Based on a review of the literature, this method may represent an alternative strategy for the treatment of giant PICA aneurysms, especially for aneurysms not suitable for direct clipping or endovascular embolization.