The impact of apparent temperature on the emergency visits for traumatic fractures in Hangzhou, China.

BACKGROUND: Traumatic fractures occur frequently worldwide. However, research remains limited on the association between short-term exposure to temperature and traumatic fractures. This study aims to explore the impact of apparent temperature (AT) on emergency visits (EVs) due to traumatic fractures. METHODS: Based on EVs data for traumatic fractures and the contemporary meteorological data, a generalized Poisson regression model along with a distributed lag nonlinear model (DLNM) were undertaken to determine the impact of AT on traumatic fracture EVs. Subgroup analysis by gender and age and sensitivity analysis were also performed. RESULTS: A total of 25,094 EVs for traumatic fractures were included in the study. We observed a wide "J"-shaped relationship between AT and risk of traumatic fractures, with AT above 9.5 °C positively associated with EVs due to traumatic fractures. The heat effects became significant at cumulative lag 0-11 days, and the relative risk (RR) for moderate heat (95th percentile, 35.7 °C) and extreme heat (99.5th percentile, 38.8 °C) effect was 1.311 (95% CI: 1.132-1.518) and 1.418 (95% CI: 1.191-1.688) at cumulative lag 0-14 days, respectively. The cold effects were consistently non-significant on single or cumulative lag days across 0-14 days. The heat effects were higher among male and those aged 18-65 years old. The sensitivity analysis results remained robust. CONCLUSION: Higher AT is associated with cumulative and delayed higher traumatic fracture EVs. The male and those aged 18-65 years are more susceptible to higher AT.

Targeting macrophagic PIM-1 alleviates osteoarthritis by inhibiting NLRP3 inflammasome activation via suppressing mitochondrial ROS/Cl- efflux signaling pathway.

BACKGROUND: Osteoarthritis (OA), in which macrophage-driven synovitis is considered closely related to cartilage destruction and could occur at any stage, is an inflammatory arthritis. However, there are no effective targets to cure the progression of OA. The NOD-, LRR-,and pyrin domain-containing protein 3 (NLRP3) inflammasome in synovial macrophages participates in the pathological inflammatory process and treatment strategies targeting it are considered to be an effective approach for OA. PIM-1 kinase, as a downstream effector of many cytokine signaling pathways, plays a pro-inflammatory role in inflammatory disease. METHODS: In this study, we evaluated the expression of the PIM-1 and the infiltration of synovial macrophages in the human OA synovium. The effects and mechanism of PIM-1 were investigated in mice and human macrophages stimulated by lipopolysaccharide (LPS) and different agonists such as nigericin, ATP, Monosodium urate (MSU), and Aluminum salt (Alum). The protective effects on chondrocytes were assessed by a modified co-culture system induced by macrophage condition medium (CM). The therapeutic effect in vivo was confirmed by the medial meniscus (DMM)-induced OA in mice. RESULTS: The expression of PIM-1 was increased in the human OA synovium which was accompanied by the infiltration of synovial macrophages. In vitro experiments, suppression of PIM-1 by SMI-4a, a specific inhibitor, rapidly inhibited the NLRP3 inflammasome activation in mice and human macrophages and gasdermin-D (GSDME)-mediated pyroptosis. Furthermore, PIM-1 inhibition specifically blocked the apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization in the assembly stage. Mechanistically, PIM-1 inhibition alleviated the mitochondrial reactive oxygen species (ROS)/chloride intracellular channel proteins (CLICs)-dependent Cl- efflux signaling pathway, which eventually resulted in the blockade of the ASC oligomerization and NLRP3 inflammasome activation. Furthermore, PIM-1 suppression showed chondroprotective effects in the modified co-culture system. Finally, SMI-4a significantly suppressed the expression of PIM-1 in the synovium and reduced the synovitis scores and the Osteoarthritis Research Society International (OARSI) score in the DMM-induced OA model. CONCLUSIONS: Therefore, PIM-1 represented a new class of promising targets as a treatment of OA to target these mechanisms in macrophages and widened the road to therapeutic strategies for OA.

Percutaneous transforaminal endoscopic discectomy for the treatment of lateral recess stenosis secondary occurred the discal fungus infection.

BACKGROUND: This is a case of lateral recess stenosis secondary occurred the discal fungus infection treated with percutaneous transforaminal endoscopic discectomy (PTED). There has been no relevant reports before. CASE PRESENTATION: A 49-year-old patient who had taken itraconazole for 13 months for lateral recess stenosis secondary occurred the discal fungus infection complained of gradually worsening radiating pain and numbness in the back and inguinal and inner thigh region of right side. In order to relieve the radiating neuralgia and reduce the damage to spinal stability, the minimally invasive PTED was performed.The patient's prognosis was assessed using Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS). During the follow-up, the patient's ODI and VAS scores were decreased significantly. The radiating pain in the inguinal and inner thigh region of right side were significantly alleviated and the discomfort caused by lower back instability was improved by plaster vest. DISCUSSION AND CONCLUSION: PTED not only avoids further damage to the stability of the lumbar spine, but also effectively relieves the symptoms of leg neuroradialgia caused by lateral recess stenosis secondary occurred the discal fungus infection.

Inhibition of NLRP3 inflammasome attenuates spinal cord injury-induced lung injury in mice.

Spinal cord injury (SCI) is one kind of severe traumatic injury, resulting in systemic inflammatory response syndrome and secondary lung injury, which is an important pathological basis of respiratory complications. The nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome is an important cytosolic protein complex in many inflammatory diseases. Hence, it is inescapable to explore the effect of inhibition of NLRP3 inflammasome by inhibitors in a mouse SCI model, which was conducted by using the method of 30-G closing force aneurysm clipping at T6-T7 spinal segment for 1 min, followed by assessment of edema, histology, alveolar type II cell apoptosis, mitochondrial dysfunction, and neutrophil infiltration. In brief, our results showed that, NLRP3 inflammasome inhibitor BAY 11-7082 or A438079 inhibited activation of NLRP3 inflammasome, alleviated mitochondrial dysfunction, the number of macrophage and neutrophil, thereby attenuating alveolar type II cell apoptosis, lung edema, and histological injury. Taken together, our data reveal that NLRP3 inflammasome inhibitor BAY 11-7082 or A438079 attenuates the inflammatory response, reverses mitochondrial dysfunction, and subsequently alleviates secondary lung injury following SCI.

Effect of CXCR4 on Apoptosis in Osteosarcoma Cells via the PI3K/Akt/NF-κß Signaling Pathway.

BACKGROUND/AIMS: Osteosarcoma, the most common primary bone malignancy, arises from primitive transformed cells of mesenchymal origin with the worldwide increasing morbidity and mortality. Previous studies found apoptosis of osteosarcoma cells was essential for an effective manner to improve the progress of osteosarcoma, and CXCR4 has been demonstrated to be relevant with various tumor progress and metastasis. METHODS: The proliferation of cells transfected with CXCR4 shRNA and control shRNA were measured by BrdU assay. Apoptosis was detected by flow cytometry. Apoptotic protein expression levels were detected by Western blot. Caspase activity was detected by Colorimetric Assay Kits using microplate reader. Activation of NF-κß signaling after CXCR4 down-regulation in osteosarcoma cells was examined by constructing NF-κß promoter luciferase reporter plasmid. The expression and activation of NF-κß Signaling relevant protein were analyzed to investigate the relationship between Akt and NF-κß signaling after the down-regulation of CXCR4 in osteosarcoma cells. RESULTS: Down-regulation of CXCR4 significantly reduced the cell proliferation, while remarkably increased the cell apoptosis and apoptotic protein expression levels in osteosarcoma cells. Furthermore, down-regulation of CXCR4 induced cell apoptosis was caspase dependent in osteosarcoma cells. This study also showed CXCR4 down-regulation induced apoptosis through inhibiting PI3K/Akt/NF-κß signaling pathway. In addition, endoplasmic reticulum stress (ERS) activation was involved in cell apoptosis induced down-regulation of CXCR4. Knockdown of partial ERS relevant proteins followed down-regulation of CXCR4 significantly inhibited cell apoptosis and the apoptotic protein expression levels. CONCLUSIONS: Taken together, the results demonstrated that down-regulation of CXCR4 could induce apoptosis of human osteosarcoma cells through inhibiting PI3K/Akt/NF-κß signaling pathway, indicating that CXCR4 could be vital for the clinical therapy of osteosarcoma.

Mitochondria Targeted Peptide Attenuates Mitochondrial Dysfunction, Controls Inflammation and Protects Against Spinal Cord Injury-Induced Lung Injury.

BACKGROUND/AIMS: Spinal cord injury (SCI) is a common and devastating disease, which results in systemic inflammatory response syndrome and secondary lung injury. Mitochondrial dysfunction and inflammation are closely related to lung injury in diverse disease models. No studies have demonstrated the effects of mitochondrial targeted peptide SS-31 in a mouse model of SCI-induced lung injury. METHODS: Immediately after injury, mice in the treatment groups received a daily, single-dose intraperitoneal injection of SS-31 and for the next 2 days. The sham and SCI groups also received a daily single dose of vehicle (DMSO and 0.9% NaCl, 1: 3). The lung tissue of mice was examined after SCI, and tissue damage, apoptosis, inflammation, and mitochondrial dysfunction were recorded. RESULTS: SS-31 treatment attenuated lung edema and tissue damage. Furthermore, SS-31 treatment reduced apoptosis of alveolar type II cells, the number of total macrophages and M1 macrophages, and neutrophil infiltration. Moreover, SS-31 treatment attenuated reactive oxygen species levels, reversed mitochondrial dysfunction and inhibited NLRP3 inflammasome activation. CONCLUSIONS: Collectively, our results demonstrate that SS-31 attenuates mitochondrial dysfunction, controls inflammatory responses, and alleviates the severity of lung damage in a mouse model of SCI-induced lung injury.

Targeting the NLRP3 inflammasome to attenuate spinal cord injury in mice.

BACKGROUND: Spinal cord injury (SCI) is a devastating disease, which results in tissue loss and neurologic dysfunction. NLRP3 inflammasome plays an important role in the mechanism of diverse diseases. However, no studies have demonstrated the role of NLRP3 inflammasome and the effects of NLRP3 inflammasome inhibitors in a mouse model of SCI. We investigated whether inhibition of NLRP3 inflammasome activation by the pharmacologic inhibitor BAY 11-7082 or A438079 could exert neuroprotective effects in a mouse model of SCI. METHODS: SCI was performed using an aneurysm clip with a closing force of 30 g at the level of the T6-T7 vertebra for 1 min. Motor recovery was evaluated by an open-field test. Neuronal death was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling and Nissl staining. Mitochondrial dysfunction was determined by quantitative real-time polymerase chain reaction (qPCR), western blot, and detection of mitochondrial membrane potential level. Microglia/macrophage activation and astrocytic response were evaluated by immunofluorescence labeling. RESULTS: Inhibition of NLRP3 inflammasome activation by pharmacologic inhibitor BAY 11-7082 or A438079 reduced neuronal death, attenuated spinal cord anatomic damage, and promoted motor recovery. Furthermore, BAY 11-7082 or A438079 directly attenuated the levels of NLRP3 inflammasome and proinflammatory cytokines. Moreover, BAY 11-7082 or A438079 alleviated microglia/macrophage activation, neutrophils infiltration, and reactive gliosis, as well as mitochondrial dysfunction. CONCLUSIONS: Collectively, our results demonstrate that pharmacologic suppression of NLRP3 inflammasome activation controls neuroinflammation, attenuates mitochondrial dysfunction, alleviates the severity of spinal cord damage, and improves neurological recovery after SCI. These data strongly indicate that the NLRP3 inflammasome is a vital contributor to the secondary damage of SCI in mice.

Triptolide inhibits the growth of osteosarcoma by regulating microRNA-181a via targeting PTEN gene in vivo and vitro.

We aimed to study the anti-tumor effects of triptolide on osteosarcoma and the related molecular mechanisms. The cell viability, apoptosis portion, tumor size, tumor weight, and invasion of osteosarcoma cells were determined. The relative level of microRNA-181 in osteosarcoma tissues and the adjacent tissues was determined by quantitative real-time reverse transcription polymerase chain reaction. The target gene of microRNA-181a was determined and verified by luciferase report assay. At last, osteosarcoma cells were treated with triptolide and triptolide + microRNA-181a mimics to verify the relationship between triptolide and microRNA-181a. Triptolide inhibited the cell viability, promoted the apoptosis, decreased the tumor size and weight, and reduced the invasion of osteosarcoma cells. The level of microRNA-181a in osteosarcoma cells decreased significantly after treating with triptolide, and the relative level of microRNA-181a in osteosarcoma tissues was markedly higher than that in the adjacent tissues. PTEN was reported and verified the direct target gene of microRNA-181a. The overexpression of microRNA-181a decreased the inhibition of triptolide on osteosarcoma proliferation and promotion on osteosarcoma apoptosis. In conclusion, triptolide inhibited cell growth and invasion of osteosarcoma by regulating microRNA-181a via targeting PTEN gene in vivo and vitro.

11R-VIVIT Peptide Inhibits Calvaria Osteolysis Induced by Experimental Design.

Wear particles released from prosthetic implants can cause periprosthetic osteolysis, a major cause of implant loosening. The aim of this study was to investigate the effects of the 11R-VIVIT peptide on osteolysis induced by titanium (Ti) particles in vivo. Twenty-four C57BL/J6 mice were divided into 3 groups: sham operation, Ti group, and Ti/VIVIT group. A calvarial osteolysis model was established by implanting Ti particles into mouse calvaria of the Ti and Ti/VIVIT groups. After 2 weeks, 11R-VIVIT peptide (10 mg/kg/day) was intraperitoneally injected into the mice of the Ti/VIVIT group for 14 days. The other 2 groups received saline injection. The calvarial specimens were removed and stained with van Geison staining. The calvarial sagittal suture area was measured to observe bone resorption. The calvarial new bone area was measured to observe bone formation. Compared with the sham group, the area of calvarial new bone and calvarial sagittal suture were higher in the Ti group (P < 0.01). Compared with the Ti group, the area of calvarial new bone was higher and the area of calvarial sagittal suture was lower in the Ti/VIVIT group (P < 0.01). In conclusion, the 11R-VIVIT peptide inhibited bone resorption and enhanced bone formation. This may have contributed to lower wear particle-induced osteolysis. This method could eventually be used to prevent prosthesis loosening after joint replacement and to prolong the life of the prosthesis.

POU Class 2 Homeobox Associating Factor 1, as a Hub Candidate Gene in OP, Relieves Osteoblast Apoptosis.

Increasing evidence suggests that osteoblast apoptosis contributes to the pathogenesis of postmenopausal osteoporosis (PMOP). This study aimed to identify a hub gene associated with osteoporosis (OP) progression and its functions. We utilized the GSE68303 expression dataset from GEO database and conducted weighted gene co-expression network analysis (WGCNA) to investigate changes in co-expressed genes between sham and ovariectomy (OVX) groups. Differentially expressed genes (DEGs) were identified using the "limma" R package on GSE68303 dataset. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database. A protein-protein interaction (PPI) network was constructed using the STRING database, which was visualized by Cytoscape software. The top ten hub genes were screened using the Cytohubba plugin, among which POU class 2 homeobox associating factor 1 (POU2AF1), an OP-related hub gene, showed a significant increase in OVX-induced mouse model based on immunohistochemical staining. Inhibition of POU2AF1 suppressed cell viability, induced cell cycle arrest at the G1 phase, and promoted osteoblast apoptosis as demonstrated by CCK-8 assay, flow cytometry analysis, and TUNEL assay. Moreover, overexpression of POU2AF1 decreased cleaved caspase-3/-8/-9 expression while increasing cyclinD1 and Ki67 expression in MC3T3-E1 and hFOB1.19 cells. Therefore, POU2AF1 may serve as a potential diagnostic biomarker for slowing down the progression of OP.

Degrasyn alleviates osteoarthritis by blocking macrophagic pyroptosis via suppressing NLRP3/GSDMD signaling pathway and protecting chondrocytes.

Synovitis and cartilage destruction are crucial characteristics of osteoarthritis (OA). Inflammatory cytokines, such as IL-1ß, are secreted by synovial macrophages, leading to cartilage destruction. Pyroptosis is a lytic form of programmed cell death, which could be triggered by the NLRP3 inflammasome of macrophages. Pyroptosis promotes the secretion of IL-1ß and is supposed as a potential biomarker for OA. However, the function of Pyroptosis and NLRP3 inflammasome and its regulatory mechanism for activation is unclear in OA. In this study, we found that Degrasyn could alleviate the GSDMD-mediated pyroptosis of macrophages and the release of IL-1ß, caspase-1, and LDH. Furthermore, it selectively impedes the form of ASC oligomer and speckle to effectively suppress the NLRP3 inflammasome during its assembly phase. Notably, Degrasyn exhibited potential chondroprotective effects in a co-culture system. Additionally, these results also indicate that Degrasyn mitigates synovitis and cartilage damage in a murine model of destabilization of the medial meniscus (DMM)-induced OA. In summary, Degrasyn emerges as a promising pharmaceutical agent for synovitis, paving the way for innovative therapeutic approaches to OA. Our findings underscore the potential of Degrasyn as a viable candidate for OA therapeutics, demonstrating its ability to regulate pyroptosis and NLRP3 inflammasome activation.

Morphometric Analysis of the Ureter with Respect to Lateral Lumbar Interbody Fusion Using Contrast-Enhanced Computed Tomography.

OBJECTIVE: To analyze the anatomical location of the ureter in relation to lateral lumbar interbody fusion and evaluate the potential risk of ureteral injury. METHODS: One hundred eight patients who performed contrast-enhanced computed tomographic scans were enrolled in this study. The location of the ureter from L2-L3 to L4-L5 was evaluated. The distances between the ureter and psoas muscle, intervertebral disc, and retroperitoneal vessels were also recorded bilaterally. RESULTS: Over 30% of the ureters were close to the working corridor of extreme lumbar interbody fusion at L2-L3. Most of the ureters were close to working corridor of oblique lumbar interbody fusion, especially at L4-L5. The distance from the ureter to the great vessels on the left side was significantly narrowing from L2-L3 to L4-L5 (28.8±9.5 mm, 22.0±8.0 mm, 15.5±8.4 mm), and it was significantly larger than that on the right side (12.3±6.1 mm, 7.4±5.7 mm, 5.4±4.4 mm). CONCLUSION: Our findings indicate that the location of the ureter varies widely among individuals. To avoid unexpected damage to the ureter, it is imperative to directly visualize it and verify the ureter is not in the surgical pathway during lateral lumbar interbody fusion.

METTL14 upregulates TCF1 through m6A mRNA methylation to stimulate osteogenic activity in osteoporosis.

Alteration of N6-methyladenosine (m6A) is closely linked to spanning biological processes including osteoporosis (OP) development. This research focuses on the function of methyltransferase like 14 (METTL14) in bone turnover and its interaction with T cell factor 1 (TCF1). A mouse model of OP was established by ovariectomy (OVX). The bone mass parameters were evaluated by micro-CT analysis. Mouse MC3T3-E1 cells and mouse bone marrow macrophages (BMMs) were induced for osteogenic or osteoclastic differentiation, respectively, for in vitro experiments. The osteogenesis or osteoclasis activity was analyzed by measuring the biomarkers such as OPG, ALP, NFATC1, CTSK, RANKL, and TRAP. RT-qPCR and IHC assays identified reduced METTL14 expression in bone tissues of osteoporotic patients and ovariectomized mice. Artificial METTL14 overexpression increased bone mass of mice and promoted osteogenesis whereas suppressed osteoclasis both in vivo and in vitro. METTL14 promoted TCF1 expression through m6A mRNA methylation, and TCF1 increased the osteogenic activity by elevating the protein level of RUNX2, a key molecule linked to bone formation. In rescue experiments, TCF1 restored the RUNX2 level and osteogenic activity of cells suppressed by METTL14 silencing. In summary, this research demonstrates that METTL14 plays a protective role against OP by promoting the TCF1/RUNX2 axis.

Transforaminal Endoscopic Discectomy for Thoracolumbar Disc Herniation: A Retrospective Study and Technical Note.

BACKGROUND: Thoracolumbar disc herniation (TLDH) is a rare disorder with unique characteristics that can result in undesirable surgical outcomes after traditional discectomy. In view of the widespread use of transforaminal endoscopic discectomy for lower lumbar disc herniation, we investigated treatment of TLDH by this procedure. The purpose of this study was to evaluate the clinical efficacy of transforaminal endoscopic discectomy for treating TLDH and share our technical experience. METHODS: We retrospectively evaluated the clinical data of 19 patients who had undergone transforaminal endoscopic discectomy for TLDH in our institution between April 2018 and July 2021. Operation time, follow-up time, blood loss, postoperative hospital stay, visual analog scale scores for low-back and leg pain, and Japanese Orthopedic Association (JOA) scores were evaluated. RESULTS: The differences between preoperative and postoperative JOA and visual analog scale scores were significant (P < 0.05). According to the JOA scores, 14 of the 19 patients had excellent improvement, 3 had good improvement, and 2 had fair improvement; thus, the rate of satisfactory improvement was 89.5%. CONCLUSIONS: Operation time, blood loss, postoperative hospital stay, and surgical outcomes were favorable. Transforaminal endoscopic discectomy is an ideal surgical procedure for treating TLDH.

Extracellular vesicles from bone marrow mesenchymal stem cells alleviate osteoporosis in mice through USP7-mediated YAP1 protein stability and the Wnt/ß-catenin pathway.

Mesenchymal stem cells (MSCs) and their derived extracellular vesicles (EVs) have emerged as promising tools for promoting bone regeneration. This study investigates the functions of EVs derived from bone marrow-derived MSCs (BMSCs) in osteoporosis (OP) and the molecular mechanism. EVs were isolated from primary BMSCs in mice. A mouse model with OP was induced by ovariectomy. Treatment with EVs restored bone mass and strength, attenuated trabecular bone loss and cartilage damage, and increased osteogenesis while suppressing osteoclastogenesis in ovariectomized mice. In vitro, the EVs treatment improved the osteogenic differentiation of MC-3T3 while inhibiting osteoclastic differentiation of RAW264.7 cells. Microarray analysis revealed a significant upregulation of ubiquitin specific peptidase 7 (USP7) expression in mouse bone tissues following EV treatment. USP7 was found to interact with Yes1 associated transcriptional regulator (YAP1) and stabilize YAP1 protein through deubiquitination modification. YAP1-related genes were enriched in the Wnt/ß-catenin signaling, and overexpression of YAP1 promoted the nuclear translocation of ß-catenin. Functional experiments underscored the critical role of maintaining USP7, YAP1, and ß-catenin levels in the pro-osteogenic and anti-osteoclastogenic properties of the BMSC-EVs. In conclusion, this study demonstrates that USP7, delivered by BMSC-derived EVs, stabilizes YAP1 protein, thereby ameliorating bone formation in OP through the Wnt/ß-catenin activation.

Comparison of minimally invasive transforaminal lumbar interbody fusion and endoscopic lumbar interbody fusion for lumbar degenerative diseases: a retrospective observational study.

BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and endoscopic lumbar interbody fusion (Endo-LIF) are both minimally invasive interbody fusion procedures for lumbar degenerative diseases. In this study, we attempted to compare the clinical efficacy and postoperative outcomes of MIS-TLIF and Endo-LIF for lumbar degenerative diseases. METHODS: The study cohort comprised 99 patients with lumbar degenerative diseases treated by MIS-TLIF or Endo-LIF from January 2019 to July 2021. The clinical outcomes (visual analogue scale (VAS), Oswestry disability index (ODI), and MacNab criteria) preoperatively, 1 month postoperatively, 3 months postoperatively, and 1 year postoperatively were compared between the two groups. RESULTS: There were no significant differences between the two groups in sex, age, disease duration, affected spine segment, and complications (P > 0.05). The operation time was significantly longer in the Endo-LIF group than the MIS-TLIF group (155.25 ± 12.57 vs. 123.14 ± 14.50 min; P < 0.05). However, the Endo-LIF group had a significantly smaller blood loss volume (61.79 ± 10.09 vs. 259.97 ± 14.63 ml) and shorter hospital stay (5.46 ± 1.11 vs. 7.06 ± 1.42 days) than the MIS-TLIF group. In both groups, the ODI and VAS scores for lower back pain and leg pain were significantly lower at each postoperative timepoint than preoperatively (P < 0.05). Although there were no significant differences between the two groups in the ODI and VAS scores for lower back pain and leg pain (P > 0.05), the VAS for lower back pain was lower in the Endo-LIF group than the MIS-TLIF group at each postoperative timepoint. The MacNab criteria showed that the improvement rate was 92.2% in the MIS-TLIF group and 91.7% in the Endo-LIF group, with no significant difference between the two groups (P > 0.05). CONCLUSIONS: There were no significant differences in short-term surgical outcomes between the MIS-TLIF and Endo-LIF groups. Compared with the MIS-TLIF group, the Endo-LIF group incurred less damage to surrounding tissues, experienced less intraoperative blood loss, and had less lower back pain, which is more conducive to recovery.

Intermittent Hydrostatic Pressure Promotes Cartilage Repair in an Inflammatory Environment through Hippo-YAP Signaling In Vitro and In Vivo.

The study of chondrogenic progenitor cells (CPCs) as seed cells has become a new focus of cartilage regeneration. The inflammatory environment of osteoarthritis (OA) inhibits the repair ability of CPCs. But the OA patients' CPCs showed an excellent regeneration ability with intermittent hydrostatic pressure (IHP). However, the mechanism is unclear. We compared the expression of the Hippo signaling effect factor YAP between OA and normal cartilages. Then, the relationship between the Kellgren-Lawrence (K-L) score of OA and the rate of YAP-positive cells was analyzed. The changes of CPCs after IHP and IL-1ß applications were observed. The OA model was established by cutting the anterior cruciate ligament of rats. The knee joint of the OA rats was distracted by hinged external fixator to create suitable IHP, named as the IHP group. The IHP group plus intra-articular injection of Verteporfin (VP) was named as the IHP+VP group, and the untreated rat group was named as the CON group. Four and 8 weeks after the operation, the reparative effect was evaluated by MASSON staining and immunohistochemical staining. Lower levels of YAP1 and higher expressions of p-YAP1 were found in the OA group as compared to the normal group. IHP inhibited the Hippo signaling in an inflammatory environment and promoted the proliferation of CPCs. The cartilage deterioration in the CON group progressed more significantly than that in the IHP+VP group. The best reparative effect was observed in the IHP group with increased expression of YAP1 and decreased p-YAP1. These results hint that mechanical stress can activate CPCs and promote cartilage repair in an inflammatory environment through inhibiting Hippo signaling.

Radiosensitizing Effect of Celastrol by Inhibiting G2/M Phase Arrest Induced by the c-myc Gene of Human SW1353 Chondrosarcoma Cells: Network and Experimental Analyses.

OBJECTIVE: Studies have unveiled that the components of Tripterygium wilfordii Hook F (TWHF) such as celastrol could attenuate apoptosis and proliferation of various tumor cells. This study is focused on the radiosensitization effect and apoptotic pathways of celastrol via the inhibition of the c-myc gene and the influence of which combined with radiotherapy on the proliferation, apoptosis, invasion, and metastasis of chondrosarcoma cells. METHODS: A variety of bioinformatic tools were applied to explore the expression level and prognosis of the c-myc gene in different tumor cells and chondrosarcoma cells. We used pharmacology network to analyze the components, pathways, targets, molecular functions of TWHF and explore the relevant effective components over the MYC gene. Clone formation assay, CCK-8 assay, flow cytometry, and transwell migration assay were applied to detect the effects of celastrol on the expression of c-myc gene, cell apoptosis, and cell cycle. Radiation therapy was used to observe the radiosensitization effect of celastrol on chondrosarcoma. RESULTS: This study shows that the c-myc gene is overexpressed in various tumor cells and bone tumor cells to varying degrees. Celastrol can significantly inhibit the expression of the c-myc gene, induce G2/M phase arrest through regulation of G2/M phase-related proteins, and promote SW1353 cell apoptosis through the mitochondrial signaling pathway. In addition, we also found that the use of triptorubin to inhibit c-myc gene expression in combination with radiotherapy can increase the osteosarcoma cells' apoptosis rate through the mitochondrial signaling pathway significantly. CONCLUSIONS: Our study validated the radiosensitization effect of celastrol through knocking down the expression of the c-myc gene to induce G2/M phase arrest and provides a new idea for the treatment of refractory or recurrent chondrosarcoma that is not sensitive to radiotherapy.

[Application of enriched bone marrow compound with fibrin glue in repairing old radial bone defect in rabbits].

OBJECTIVE: To explore the feasibility of using enriched bone marrow (BM) compound with fibrin glue (FG) in repairing old radial bone defect. METHODS: Totally 36 New Zealand rabbits were equally randomized into three groups: simple FG group, BM+FG group, and enriched BM+FG group. A 1.5-cm segmental bone defect was made at the left radial in each animal. After one month, the defect was implanted with the engineered bone. Before implantation, a compound of enriched BM with FG underwent electron microscopy, long-term culture, and bacteriological culture. Four, 8, and 12 weeks after operations, the osteogenetic effect was evaluated using X-ray observation, HE staining, or Van Gieson staining, and a semi-quantitative analysis was performed. RESULTS: Electron microscopy showed enriched BM were compatible well with FG. No bacterial contamination or oncogenicity was observed after long-term culture. X-ray showed the repair effectiveness was significantly higher in BM+FG group and enriched BM+FG group than in simple FG group. Eight and 12 weeks after surgery, the Yang scores were significantly higher in enriched BM+FG group than in BM+FG group [(9.348±0.364évs.(7.984±0.229éìF=40.167ìP=0.001; (12.664±0.388)vs. (10.584±0.836é, F=20.3647ìP=0.004]. In addition, the Yang's scores at bone defects in BM+FG group and enriched BM+FG group were higher at the 12(th) week than in the 8(th) week. (F=36.004ìP=0.001; F=155.141ìP=0.000; respectively)The bone defects were repaired at varied degrees were histologically observed in BM+FG group and enriched BM+FG group during the observations. CONCLUSION: Implantation of BM+FG or enriched BM+FG are effective in repairing old radial bone defects, while simple FG shows not such effect.