Effect of ultrasonic surface impact on the microstructural characterization and mechanical properties of 316L austenitic stainless steel.

In the present study, effect of ultrasonic impact treatment (UIT) on the microstructural characterization and mechanical properties of 316L stainless steel (hereinafter referred to as 316L) was investigated experimentally. The fatigue fracture mechanism of 316L before and after UIT was revealed. The experimental results indicated that the martensitic grain size induced at the impact edge was about 2.00 Å. The surface modified 316L formed a gradient nanostructure and induced a martensitic phase transformation. The hardness of the surface layer of the modified 316L was twice the hardness of its matrix. The tensile strengths of 316L before and after UIT were 576 MPa and 703 MPa, respectively. The stretching stripes of 316L were more disordered after UIT. The fatigue strengths of 316L before and after UIT were 267 MPa and 327 MPa, respectively. The fatigue cracking of 316L started from the austenite grain boundaries. The fatigue fracture surface was relatively rough. The fatigue crack sources of the modified 316L came from internal inclusions. The inclusions were oxides dominated by SiO2. As the stress range increased, the crack initiation site migrated to the interior and the fatigue fracture surface became flatter.

Ruxolitinib improves the inflammatory microenvironment, restores glutamate homeostasis, and promotes functional recovery after spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202419110-00030/figure1/v/2024-03-08T184507Z/r/image-tiff The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury. Ruxolitinib, a JAK-STAT inhibitor, exhibits effectiveness in autoimmune diseases, arthritis, and managing inflammatory cytokine storms. Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma, the exact mechanism by which it enhances functional recovery after spinal cord injury, particularly its effect on astrocytes, remains unclear. To address this gap, we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury. Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury, restored EAAT2 expression, reduced glutamate levels, and alleviated excitatory toxicity. Furthermore, ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1ß, interleukin-6, and tumor necrosis factor-α. Additionally, in glutamate-induced excitotoxicity astrocytes, ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3, thereby reducing glutamate-induced neurotoxicity, calcium influx, oxidative stress, and cell apoptosis, and increasing the complexity of dendritic branching. Collectively, these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes, reduces neurotoxicity, and effectively alleviates inflammatory and immune responses after spinal cord injury, thereby promoting functional recovery after spinal cord injury.

Multiomics analysis of metabolic heterogeneity in cervical cancer cell lines with or without HPV.

Metabolomics analysis revealed the metabolic heterogeneity of cervical cancer (CC) cell lines C33A and CaSki, and their molecular mechanisms were explored. Using the modified Bligh-Dyer method, the endogenous metabolites of C33A and CaSki cells were divided into polar and nonpolar fractions. The metabolites were analysed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Then, the differential metabolites were screened by combining multivariate statistical analysis and volcano maps, and functional enrichment and pathway analysis of the differential metabolites were performed. Finally, association analysis was carried out in combination with transcriptomics, and the important differential metabolisms were experimentally verified by real-time PCR (RT-qPCR) and oil red staining. The results showed that between the C33A and CaSki cell lines, there were significant differences in amino acids, nucleotides and lipids, such as in threonine, arachidonic acid and hypoxanthine, in the metabolic pathways. These compounds could be used as markers of differences in cellular metabolism. The heterogeneity of lipid metabolism accounted for 87.8%, among which C33A cells exhibited higher contents of fatty acid polar derivatives, while CaSki cells showed higher contents of free fatty acids and glycerides. Based on correlation analysis of the above metabolic differences in HPV pathways as well as lipid metabolism-related genes, p53 and the genes involved in lipid metabolism pathways, such as Peroxisome Proliferator Activated Receptor Gamma(PPARG) and stearoyl-CoA desaturase (SCD), are relevant to the metabolic heterogeneity of the cells. The differential expression of some genes was validated by RT-qPCR. CaSki cells showed significantly higher glyceride levels than that of C33A cells, as verified by oil red O staining and glyceride assays. The above results showed that the metabolomic differences between C33A and CaSki cells were relatively obvious, especially in lipid metabolism, which might be related to the decreased expression of PPARG and p53 caused by HPV E6. Further studies on the molecular mechanism of lipid metabolism heterogeneity in cervical cancer cell lines with or without HPV could provide a new reference for the development of CC and individualized treatments of tumour patients.

Corrigendum: miR-766-3p targeting BCL9L suppressed tumorigenesis, epithelial-mesenchymal transition, and metastasis through the ß-catenin signaling pathway in osteosarcoma cells.

[This corrects the article DOI: 10.3389/fcell.2020.594135.].

Necroptosis-related LncRNAs in skin cutaneous melanoma: evaluating prognosis, predicting immunity, and guiding therapy.

BACKGROUND: An increasing amount of research has speculated that necroptosis could be a therapeutic strategy for treating cancer. However, understanding the prognostic value of the necroptosis-related long non-coding RNAs (NRLs) in skin cutaneous melanoma (SKCM, hereafter referred to as melanoma) remains poor and needs to be developed. Our research aims to construct a model based on NRLs for the prognosis of patients with melanoma. METHODS: We obtained the RNA-seq and clinical data from The Cancer Genome Atlas (TCGA) database and retrieved 86 necroptosis-related genes from the GeneCards database. The lncRNAs associated with necroptosis were identified via the Pearson correlation coefficient, and the prognostic model of melanoma was constructed using LASSO regression. Next, we employed multiple approaches to verify the accuracy of the model. Melanoma patients were categorized into two groups (high-risk and low-risk) according to the results of LASSO regression. The relationships between the risk score and survival status, clinicopathological correlation, functional enrichment, immune infiltration, somatic mutation, and drug sensitivity were further investigated. Finally, the functions of AL162457.2 on melanoma proliferation, invasion, and migration were validated by in vitro experiments. RESULTS: The prognostic model consists of seven NRLs (EBLN3P, AC093010.2, LINC01871, IRF2-DT, AL162457.2, AC242842.1, HLA-DQB1-AS1) and shows high diagnostic efficiency. Overall survival in the high-risk group was significantly lower than in the low-risk group, and risk scores could be used to predict melanoma survival outcomes independently. Significant differences were evident between risk groups regarding the expression of immune checkpoint genes, immune infiltration, immunotherapeutic response and drug sensitivity analysis. A series of functional cell assays indicated that silencing AL162457.2 significantly inhibited cell proliferation, invasion, and migration in A375 cells. CONCLUSION: Our prognostic model can independently predict the survival of melanoma patients while providing a basis for the subsequent investigation of necroptosis in melanoma and a new perspective on the clinical diagnosis and treatment of melanoma.

[Herniation of intervertebral disc into thoracolumbar fracture vertebral body leads to malunion of fracture and decrease of intervertebral space height].

OBJECTIVE: To analyze the clinical characteristics of intervertebral disc tissue injury and herniation into the vertebral body in thoracolumbar fracture on fracture healing, vertebral bone defect volume and intervertebral space height. METHODS: From April 2016 to April 2020, a total of 140 patients with thoracolumbar single vertebral fracture combined with upper intervertebral disc injury treated with pedicle screw rod system reduction and internal fixation in our hospital. There were 83 males and 57 females, aged from 19 to 58 years old, with an average age of (39.33±10.26) years old. All patients were followed up regularly 6 months, 12 months and 18 months after surgery. The patients with injured intervertebral disc tissue not herniated into the fractured vertebral body were the control group, and the patients with injured intervertebral disc and herniated into the fractured vertebral body were the observation group. By detecting the thoracolumbar AP and lateral X-ray films, CT and MRI of the thoracolumbar segment at different follow-up time, calculate the changes of the wedge angle of the fractured vertebral body, the sagittal kyphosis angle and the height of the superior adjacent intervertebral space, the changes of the fracture healing and bone defect volume after the reduction of the vertebral body, and the changes of the intervertebral disc degeneration grade. The prognosis was evaluated by visual analogue scale(VAS) and Oswestry disability index(ODI). Finally, the differences of the above results among different groups were comprehensively analyzed. RESULTS: All the patients had normal wound healing without complications. A total of 87 patients received complete follow-up data, at least 18 months after internal fixation. Thoracolumbar AP and lateral X-ray films showed that 18 months after the reduction and internal fixation operation, the vertebral wedge angle, sagittal kyphosis angle and the height of the upper adjacent intervertebral space in the observation group were greater than those in the control group(P<0.05). CT scanning showed that the deformity of the fracture healed 12 months after the vertebral body reduction in the observation group and formed a "cavity" of bone defect connected with the intervertebral space, and its volume was significantly increased compared with that before (P<0.05). MRI scanning showed that the degeneration rate of injured intervertebral discs in the observation group was more serious than that in the control group 12 months after operation(P<0.05). However, there was no significant difference in VAS and ODI score at each time. CONCLUSION: Herniation of injured intervertebral disc tissue hernias into the fractured vertebral body leads to increased bone resorption defect volume around the fracture and forms a malunion "cavity" connected with the intervertebral space. This may be the main reason for the change of vertebral wedge angle, the increase of sagittal kyphosis angle and the decrease of intervertebral space height after removal of internal fixation devices.

USP1/UAF1-Stabilized METTL3 Promotes Reactive Astrogliosis and Improves Functional Recovery after Spinal Cord Injury through m6A Modification of YAP1 mRNA.

RNA N6-methyladenosine (m6A) modification is involved in diverse biological processes. However, its role in spinal cord injury (SCI) is poorly understood. The m6A level increases in injured spinal cord, and METTL3, which is the core subunit of methyltransferase complex, is upregulated in reactive astrocytes and further stabilized by the USP1/UAF1 complex after SCI. The USP1/UAF1 complex specifically binds to and subsequently removes K48-linked ubiquitination of the METTL3 protein to maintain its stability after SCI. Moreover, conditional knockout of astrocytic METTL3 in both sexes of mice significantly suppressed reactive astrogliosis after SCI, thus resulting in widespread infiltration of inflammatory cells, aggravated neuronal loss, hampered axonal regeneration, and impaired functional recovery. Mechanistically, the YAP1 transcript was identified as a potential target of METTL3 in astrocytes. METTL3 could selectively methylate the 3'-UTR region of the YAP1 transcript, which subsequently maintains its stability in an IGF2BP2-dependent manner. In vivo, YAP1 overexpression by adeno-associated virus injection remarkably contributed to reactive astrogliosis and partly reversed the detrimental effects of METTL3 knockout on functional recovery after SCI. Furthermore, we found that the methyltransferase activity of METTL3 plays an essential role in reactive astrogliosis and motor repair, whereas METTL3 mutant without methyltransferase function failed to promote functional recovery after SCI. Our study reveals the previously unreported role of METTL3-mediated m6A modification in SCI and might provide a potential therapy for SCI.SIGNIFICANCE STATEMENT Spinal cord injury is a devastating trauma of the CNS involving motor and sensory impairments. However, epigenetic modification in spinal cord injury is still unclear. Here, we propose an m6A regulation effect of astrocytic METTL3 following spinal cord injury, and we further characterize its underlying mechanism, which might provide promising strategies for spinal cord injury treatment.

Comparison of a directional cement delivery device versus conventional device in unilateral percutaneous kyphoplasty for the therapy of osteoporotic thoracolumbar fracture in the elderly.

BACKGROUND: Percutaneous kyphoplasty (PKP) has been demonstrated to be effective in the treatment of osteoporotic vertebral compression fractures (OVCF). However, bilateral puncture techniques take more time to accept more X-ray radiation; some spinal surgeons apply unilateral puncture PKP, but the cement cannot be symmetrically distributed in the vertebral body, so we apply a directional bone cement delivery device that undergoes PKP through the unilateral pedicle puncture. This research aims to compare the clinical and radiological results of PKP via unilateral pedicle approach using a traditional bone cement delivery device and a directional bone cement delivery device and determine the value of a directional delivery device for the therapy of thoracolumbar compression fracture in the elderly. METHODS: We undertook a retrospective analysis of patients with single-level OVCF treated with unilateral pedicle puncture PKP from Jan 2018 to Jan 2020. Operation time, radiation exposure, bone cement injection volume, and the incidence of bone cement leakage were recorded for presentation, and the cement leakage and bone cement distribution were measured by X-ray and computed tomography scan. The patients were followed up postoperatively and were assessed mainly with regard to clinical and radiological outcomes. RESULTS: There was no significant difference in the operation time, radiation exposure time, and incidence of bone cement leakage between the two groups. A significant difference was observed in the volume of bone cement injection between the two groups. All patients in both groups had significantly less pain after the procedures, compared with their preoperative period pain. There were no significant differences in Visual Analogue Scale, the relative height of the vertebral body, Cobb angle, and Quality of Life Questionnaire of the European Foundation for Osteoporosis between the two groups at 1 week after PKP, significant difference was observed only 12 months after operation. CONCLUSION: Application of directional bone cement delivery device is safe and feasible, compared with the application of traditional bone cement delivery device, without prolonging the operative time, radiation exposure time, and the incidence of bone cement leakage. It has the advantages of good short- and medium-term effect, excellent bone cement distribution, and low incidence of kyphosis recurrence.

Development and Clinical Trial of a New Orthopedic Surgical Robot for Positioning and Navigation.

Robot-assisted orthopedic surgery has great application prospects, and the accuracy of the robot is the key to its overall performance. The aim of this study was to develop a new orthopedic surgical robot to assist in spinal surgeries and to compare its feasibility and accuracy with the existing orthopedic robot. A new type of high-precision orthopedic surgical robot (Tuoshou) was developed. A multicenter, randomized controlled trial was carried out to compare the Tuoshou with the TiRobot (TINAVI Medical Technologies Co., Ltd., Beijing) to evaluate the accuracy and safety of their navigation and positioning. A total of 112 patients were randomized, and 108 patients completed the study. The position deviation of the Kirschner wire placement in the Tuoshou group was smaller than that in the TiRobot group (p = 0.014). The Tuoshou group was better than the TiRobot group in terms of the pedicle screw insertion accuracy (p = 0.016) and entry point deviation (p < 0.001). No differences were observed in endpoint deviation (p = 0.170), axial deviation (p = 0.170), sagittal deviation (p = 0.324), and spatial deviation (p = 0.299). There was no difference in security indicators. The new orthopedic surgical robot was highly accurate and optimized for clinical practice, making it suitable for clinical application.

Decoding the spatial chromatin organization and dynamic epigenetic landscapes of macrophage cells during differentiation and immune activation.

Immunocytes dynamically reprogram their gene expression profiles during differentiation and immunoresponse. However, the underlying mechanism remains elusive. Here, we develop a single-cell Hi-C method and systematically delineate the 3D genome and dynamic epigenetic atlas of macrophages during these processes. We propose "degree of disorder" to measure genome organizational patterns inside topologically-associated domains, which is correlated with the chromatin epigenetic states, gene expression, and chromatin structure variability in individual cells. Furthermore, we identify that NF-κB initiates systematic chromatin conformation reorganization upon Mycobacterium tuberculosis infection. The integrated Hi-C, eQTL, and GWAS analysis depicts the atlas of the long-range target genes of mycobacterial disease susceptible loci. Among these, the SNP rs1873613 is located in the anchor of a dynamic chromatin loop with LRRK2, whose inhibitor AdoCbl could be an anti-tuberculosis drug candidate. Our study provides comprehensive resources for the 3D genome structure of immunocytes and sheds insights into the order of genome organization and the coordinated gene transcription during immunoresponse.

Oil Displacement by the Magnetic Fluid Inside a Cylindrical Sand-Filled Sample: Experiments and Numerical Simulations.

Magnetic fluid is a new type of smart material, which holds implications for highly enhancing the oil displacement efficiency. In the present study, we perform a comprehensive investigation to probe the influence of a magnetic fluid on the displacement efficiency in porous media under the action of magnetic force. First, the displacement efficiency is measured by a self-developed setup, where factors such as the magnet thicknesses, the volume of the fluid injected, the fluid injection speed, and the porosity of the sample are surveyed as controllable variables. Moreover, the experimental results are well verified by the scaling laws according to the principle of dimensional balance. Next, a numerical simulation is performed to explore the detailed displacement process. First, the magnetic force generated by the ring magnet is calculated. Then, the function curves of the displacement efficiency with respect to the controlling variables are validated by the numerical simulation. In addition, the numerical simulation also demonstrates the volume phase distribution, the pressure field, and the velocity field of the mixed fluid during the displacement process. The simulation results are in excellent agreement with the experimental data. These findings are beneficial for us to better understand the oil displacement with the aid of external fields, which also provide inspiration for the areas of microfluidics, diffusion of pollutants, microsensors, etc.

JEV Infection Induces M-MDSC Differentiation Into CD3+ Macrophages in the Brain.

Japanese encephalitis virus (JEV) is one of the most important members of the flavivirus family. It is a typical zoonotic pathogen that has caused substantial social and economic losses worldwide. The relation between JEV-induced immunosuppression and inflammatory responses has not been thoroughly investigated. In this study, cells infiltrating the brain tissue of JEV-infected mice were mainly identified as monocytic myeloid-derived suppressor cells (M-MDSCs), which subsequently differentiated into CD3+ macrophages. Co-culture with T cells showed that both splenic M-MDSCs and brain infiltrated M-MDSCs isolated from JEV-infected mice inhibited T cell proliferation through ARG1 and iNOS. The splenectomy model revealed that JEV-induced M-MDSCs were mainly derived from bone marrow and migrated to the spleen and central nervous system (CNS). The results of the transcriptome analysis and IRF7-deficient mice indicated that the ZBP1-IRF7 signaling pathway stimulated by JEV RNA played a central role in the induction of M-MDSCs. M-MDSCs migrated into the CNS through the chemokine CCL2/N-CCL2 derived from astrocytes and brain infiltrated M-MDSCs differentiated into CD3+ macrophages through a mechanism mediated by M-CSF, IL-6 and IFN-γ in the brain microenvironment. These findings provide evidence for the mechanism that JEV regulates the differentiation of M-MDSCs and thereby exacerbates pathogenicity, which represents a potential therapeutic target for Japanese encephalitis (JE).

Locomotor Exercise Enhances Supraspinal Control of Lower-Urinary-Tract Activity to Improve Micturition Function after Contusive Spinal-Cord Injury.

The recovery of lower-urinary-tract activity is a top priority for patients with spinal-cord injury. Historically, locomotor training improved micturition function in both patients with spinal cord injury and animal models. We explore whether training augments such as the supraspinal control of the external urethral sphincter results in enhanced coordination in detrusor-sphincter activity. We implemented a clinically relevant contusive spinal-cord injury at the 12th thoracic level in rats and administered forced wheel running exercise for 11 weeks. Awake rats then underwent bladder cystometrogram and sphincter electromyography recordings to examine the micturition reflex. Subsequently, pseudorabies-virus-encoding red fluorescent protein was injected into the sphincter to trans-synaptically trace the supraspinal innervation of Onuf's motoneurons. Training in the injury group reduced the occurrence of bladder nonvoiding contractions, decreased the voiding threshold and peak intravesical pressure, and shortened the latency of sphincter bursting during voiding, leading to enhanced voiding efficiency. Histological analysis demonstrated that the training increased the extent of spared spinal-cord tissue around the epicenter of lesions. Compared to the group of injury without exercise, training elicited denser 5-hydroxytryptamine-positive axon terminals in the vicinity of Onuf's motoneurons in the cord; more pseudorabies virus-labeled or c-fos expressing neurons were detected in the brainstem, suggesting the enhanced supraspinal control of sphincter activity. Thus, locomotor training promotes tissue sparing and axon innervation of spinal motoneurons to improve voiding function following contusive spinal-cord injury.

A comparison of robot-assisted and fluoroscopy-assisted kyphoplasty in the treatment of multi-segmental osteoporotic vertebral compression fractures.

Osteoporotic vertebral compression fracture (OVCF) has become a major public health issue that becomes more pressing with increasing global aging. Percutaneous kyphoplasty (PKP) is an effective treatment for OVCF. Robot-assisted PKP has been utilized in recent years to improve accuracy and reduce complications. However, the effectiveness of robot-assisted PKP in the treatment of multi-segmental OVCF has yet to be proved. This study was designed to compare the efficacy of robot-assisted and conventional fluoroscopy-assisted multi-segmental PKP. A total of 30 cases with multi-segmental OVCF between April 2019 and April 2021 were included in this study. Fifteen cases were assigned to the robot-assisted PKP group (robot group) and 15 cases to the conventional fluoroscopy-assisted PKP group (conventional fluoroscopy group). The number of fluoroscopic exposures, fluoroscopic dose, operation time, cement leakage rate, visual analog scale (VAS) score, vertebral kyphosis angle (VKA), and height of fractured vertebral body (HFV) were compared between the 2 groups. The number of fluoroscopic exposures, fluoroscopic doses, and cement leakage rates in the robot group were lower than in the conventional fluoroscopy group ( P<0.05) while the operative time in the robot group was longer than in the conventional fluoroscopy group ( P<0.05). VAS score and VKA were decreased and HFV was increased after surgery in both groups ( P<0.05). Therefore, robot-assisted PKP for the treatment of multi-segmental OVCF can reduce the number of fluoroscopic exposures, fluoroscopic doses, and cement leakage compared to conventional treatment. As such, robot-assisted PKP has good application prospects and is potentially more effective in the treatment of multi-segmental OVCF.

Ruxolitinib attenuates secondary injury after traumatic spinal cord injury.

Excessive inflammation post-traumatic spinal cord injury (SCI) induces microglial activation, which leads to prolonged neurological dysfunction. However, the mechanism underlying microglial activation-induced neuroinflammation remains poorly understood. Ruxolitinib (RUX), a selective inhibitor of JAK1/2, was recently reported to inhibit inflammatory storms caused by SARS-CoV-2 in the lung. However, its role in disrupting inflammation post-SCI has not been confirmed. In this study, microglia were treated with RUX for 24 hours and then activated with interferon-γ for 6 hours. The results showed that interferon-γ-induced phosphorylation of JAK and STAT in microglia was inhibited, and the mRNA expression levels of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-1ß, interleukin-6, and cell proliferation marker Ki67 were reduced. In further in vivo experiments, a mouse model of spinal cord injury was treated intragastrically with RUX for 3 successive days, and the findings suggest that RUX can inhibit microglial proliferation by inhibiting the interferon-γ/JAK/STAT pathway. Moreover, microglia treated with RUX centripetally migrated toward injured foci, remaining limited and compacted within the glial scar, which resulted in axon preservation and less demyelination. Moreover, the protein expression levels of tumor necrosis factor-α, interleukin-1ß, and interleukin-6 were reduced. The neuromotor function of SCI mice also recovered. These findings suggest that RUX can inhibit neuroinflammation through inhibiting the interferon-γ/JAK/STAT pathway, thereby reducing secondary injury after SCI and producing neuroprotective effects.

Rv3722c Promotes Mycobacterium tuberculosis Survival in Macrophages by Interacting With TRAF3.

Mycobacterium tuberculosis (M.tb) secretes numerous proteins to interfere with host immune response for its long-term survival. As one of the top abundant M.tb secreted proteins, Rv3722c was found to be essential for bacilli growth. However, it remains elusive how this protein interferes with the host immune response and regulates M.tb survival. Here, we confirmed that Rv3722c interacted with host TRAF3 to promote M.tb replication in macrophages. Knock-down of TRAF3 attenuated the effect of Rv3722c on the intracellular M.tb survival. The interaction between Rv3722c and TRAF3 hampered MAPK and NF-κB pathways, resulting in a significant increase of IFN-ß expression and decrease of IL-1ß, IL-6, IL-12p40, and TNF-α expression. Our study revealed that Rv3722c interacted with TRAF3 and interrupted its downstream pathways to promote M.tb survival in macrophages. These findings facilitate further understanding of the mechanism of M.tb secreted proteins in regulating the host cell immune response and promoting its intracellular survival.

A comparison of the bilateral decompression via unilateral approach versus conventional approach transforaminal lumbar interbody fusion for the treatment of lumbar degenerative disc disease in the elderly.

BACKGROUND: Bilateral decompression via unilateral approach (BDUA) is an effective surgical approach for treating lumbar degenerative diseases. However, no studies of prognosis, especially the recovery of the soft tissue, have reported using BDUA in an elderly population. The aims of these research were to investigate the early efficacy of the bilateral decompression via unilateral approach versus conventional approach transforaminal lumbar interbody fusion (TLIF) for the treatment of lumbar degenerative disc disease in the patients over 65 years of age, especially in the perioperative factors and the recovery of the soft tissue. METHODS: The clinical data from 61 aging patients with lumbar degenerative disease who received surgical treatment were retrospectively analyzed. 31 cases who received the lumbar interbody fusion surgery with bilateral decompression via unilateral approach (BDUA) were compared with 30 cases who received conventional approach transforaminal lumbar interbody fusion. The radiographic parameters were measured using X-ray including lumbar lordosis angle and fusion rate. Japanese Orthopedic Association (JOA), Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores were used to evaluate the clinical outcomes at different time points. Fatty degeneration ratio and area of muscle/vertebral body were used to detect recovery of soft tissue. RESULTS: The BDUA approach group was found to have significantly less intraoperative blood loss(p < 0.05) and postoperative drainage(p < 0.05) compared to conventional approach transforaminal lumbar interbody fusion group. Symptoms of spinal canal stenosis and nerve compression were significantly relieved postoperatively, as compared with the preoperative state. However, the opposite side had a lower rate of fatty degeneration (9.42 ± 3.17%) comparing to decompression side (11.68 ± 3.08%) (P < 0.05) six months after surgery in the BDUA group. While there were no significant differences (P > 0.05) in two sides of conventional transforaminal lumbar interbody fusion approach group six months after surgery. CONCLUSIONS: Bilateral decompression via unilateral approach (BDUA) is able to reduce the intraoperative and postoperative body fluid loss in the elderly. The opposite side of decompression in BDUA shows less fatty degeneration in 6 months, which indicates better recovery of the soft tissue of the aging patients.

MICAL2 regulates myofibroblasts differentiation in epidural fibrosis via SRF/MRTF-A signaling pathway.

AIM: To determine the role of MICAL2 in myofibroblasts differentiation and epidural fibrosis. BACKGROUND: Epidural fibrosis (EF) may develop following laminectomy and aberrant myofibroblasts differentiation and excessive extracellular matrix (ECM) accumulation play key roles in the formation of EF. Dense epidural fibrosis results to the poor surgical outcomes and failed back surgery syndrome (FBSS), and there is no effective treatment available. Molecule interacting with Casl2 (MICAL2) has been demonstrated to participate in multiple cellular processes by regulating actin cytoskeleton dynamics. However, its role in epidural fibrosis remains totally unverified. MATERIALS AND METHODS: The potential functions and mechanisms of MICAL2 were explored using western blotting, immunofluorescence and lentivirus infection. KEY FINDINGS: In our study, we determined that the MICAL2 expression was elevated in epidural fibrotic tissues and TGF-ß1-stimulated fibroblasts. Moreover, knockdown of MICAL2 using MICAL2-specific short hairpin RNA attenuated TGF-ß1-induced myofibroblasts differentiation and epidural fibrosis both in vitro and vivo, as indicated by decreased scar formation, reduced collagen production and down-regulated expression of α-SMA, collagen-1 and fibronectin. We also demonstrated that MICAL2 knockdown affected the migratory capability of fibroblasts in vitro. By further mechanistic research, we revealed that the MRTF-A nuclear translocation was inhibited in response to the knockdown of MICAL2 in fibroblasts and MICAL2 served as a pro-fibrotic factor in an SRF/MRTF-A-dependent manner. SIGNIFICANCE: In conclusion, our results indicated that MICAL2 mediated myofibroblasts differentiation and promoted epidural fibrogenesis via SRF/MRTF-A signaling pathway, suggesting manipulation of MICAL2 activity as a novel alternative strategy for the prevention of epidural fibrosis.

Effectiveness of Tirobot-assisted vertebroplasty in treating thoracolumbar osteoporotic compression fracture.

BACKGROUND: Percutaneous kyphoplasty is the main method in the treatment of thoracolumbar osteoporotic compression fractures. However, much radiation exposure during the operation harms the health of surgeons and patients. In addition, the accuracy of this surgery still needs to be improved. This study aimed to assess the radiation exposure and clinical efficacy of Tirobot-assisted vertebroplasty in treating thoracolumbar osteoporotic compression fracture. METHODS: Included in this retrospective cohort study were 60 patients (60-90 years) who had undergone unilateral vertebroplasty for thoracolumbar osteoporotic compression fracture at our hospital between June 2019 and June 2020. All showed no systemic diseases and were assigned to Tirobot group (treated with Tirobot-assisted approach) and control group (treated with traditional approach). Fluoroscopic frequency, operative duration, length of stay (LOS), post-operative complications (cement leakage, infection, and thrombosis), and pre-operative and pre-discharge indexes (VAS score, JOA score, and Cobb's angle) were compared. RESULTS: The fluoroscopic frequency (P < 0.001) and post-operative complications (P = 0.035) in Tirobot group were significantly lower than those in control group. The operative duration and LOS in the Tirobot group were shorter than those in the control group, but the differences were not statistically significant (P = 0.183). Pre-discharge VAS score and Cobb's angle decreased, and JOA increased after surgeries in both groups. These three indexes showed a significant difference after surgery in each group (P < 0.001), but not between groups (PVAS = 0.175, PCobb's = 0.585, PJOA = 0.448). CONCLUSION: The Tirobot-assisted vertebroplasty can reduce surgery-related trauma, post-operative complications, and patients' and operators' exposure to radiation. As a safe and effective strategy, this surgery can realize the quick recovery from thoracolumbar osteoporotic compression fracture.

Silencing COX-2 blocks PDK1/TRAF4-induced AKT activation to inhibit fibrogenesis during skeletal muscle atrophy.

Skeletal muscle atrophy with high prevalence can induce weakness and fatigability and place huge burden on both health and quality of life. During skeletal muscle degeneration, excessive fibroblasts and extracellular matrix (ECM) accumulated to replace and impair the resident muscle fiber and led to loss of muscle mass. Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in synthesis of prostaglandin, has been identified as a positive regulator in pathophysiological process like inflammation and oxidative stress. In our study, we found injured muscles of human subjects and mouse model overexpressed COX-2 compared to the non-damaged region and COX-2 was also upregulated in fibroblasts following TGF-ß stimulation. Then we detected the effect of selective COX-2 inhibitor celecoxib on fibrogenesis. Celecoxib mediated anti-fibrotic effect by inhibiting fibroblast differentiation, proliferation and migration as well as inactivating TGF-ß-dependent signaling pathway, non-canonical TGF-ß pathways and suppressing generation of reactive oxygen species (ROS) and oxidative stress. In vivo pharmacological inhibition of COX-2 by celecoxib decreased tissue fibrosis and increased skeletal muscle fiber preservation reflected by less ECM formation and myofibroblast accumulation with decreased p-ERK1/2, p-Smad2/3, TGF-ßR1, VEGF, NOX2 and NOX4 expression. Expression profiling further found that celecoxib could suppress PDK1 expression. The interaction between COX-2 and PDK1/AKT signaling remained unclear, here we found that COX-2 could bind to PDK1/AKT to form compound. Knockdown of COX-2 in fibroblasts by pharmacological inactivation or by siRNA restrained PDK1 expression and AKT phosphorylation induced by TGF-ß treatment. Besides, si-COX-2 prevented TGF-ß-induced K63-ubiquitination of AKT by blocking the interaction between AKT and E3 ubiquitin ligase TRAF4. In summary, we found blocking COX-2 inhibited fibrogenesis after muscle atrophy induced by injury and suppressed AKT signaling pathway by inhibiting upstream PDK1 expression and preventing the recruitment of TRAF4 to AKT, indicating that COX-2/PDK1/AKT signaling pathway promised to be target for treating muscle atrophy in the future.