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.

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.

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.

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.

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.

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.

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.

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.

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.

Effect of tumor-associated macrophages on lncRNA PURPL/miR-363/PDZD2 axis in osteosarcoma cells.

Tumor-associated macrophages (TAMs) are known to participate in osteosarcoma (OS) progression. As demonstrated in our previous research, miR-363 played a tumor inhibitory effect in OS cells via lowering the PDZ domain containing 2 (PDZD2) expression. The regulatory roles of TAMs on miR-363/PDZD2 and the internal mechanism relating to long noncoding RNA p53 upregulated regulator of P53 levels (lncRNA PURPL) are examined in this study. TAM-like macrophages were formed by inducing CD14+ peripheral blood mononuclear cells (PBMCs). The TAMs migration was detected after MG-63 cells transfected with miR-363 mimics or inhibitors. We then analyzed the regulatory activity of PURPL on miR-363 expression. We also tested the influences of PURPL overexpression/knockdown on MG-63 cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), as well as TAMs migration. Silence in PDZD2 expression was used to confirm the effects of PURPL on MG-63 cells. We successfully induced TAM-like macrophages. MG-63 cells transfecting miR-363 mimics suppressed TAMs migration while transfecting a converse effect was seen in miR-363 inhibitor. TAMs raised PURPL expression in MG-63 cells, which was an upstream regulator of miR-363. Along with TAMs migration, PURPL overexpression promoted MG-63 cell proliferation, migration, invasion, and EMT. An opposite influence was seen due to the PURPL knockdown. The silence of PDZD2 weakened the influences of PURPL overexpression on MG-63 cells and TAMs migration. On modulating the PURPL/miR-363/PDZD2 axis, TAMs-promoted OS development might be achieved.

Peptide 11R­VIVIT promotes fracture healing in osteoporotic rats.

Osteoporotic fracture healing is a complex clinical issue. The present study was conducted to investigate the repair properties of 11R­VIVIT on osteoporotic fractures and to examine the potential effects of 11R­VIVIT on osteoporotic bone marrow­derived mesenchymal stem cells (BMSCs), A rat model of osteoporotic femoral fracture was established, and the effects of the daily local injection of 11R­VIVIT or saline on fracture repairing were evaluated by micro­CT scans and H&E staining. Moreover, BMSCs from osteoporotic rats were treated with 11R­VIVIT, and the osteogenic and adipogenic differentiation of BMSCs was evaluated. The results revealed that 11R­VIVIT promoted bone formation and increased fracture healing. In addition, 11R­VIVIT promoted the differentiation of osteoporotic BMSCs into osteoblasts rather than adipocytes. Furthermore, mechanistic analysis revealed that 11R­VIVIT promoted autophagy by blocking the protein kinase B (AKT)/nuclear factor of activated T­cells (NFATc1) signaling pathway. Consistently, the activation and inhibition of autophagy using rapamycin and LY294002 confirmed the regulatory effects of 11R­VIVIT on autophagy. On the whole, the findings of the present study demonstrate that 11R­VIVIT promotes fracture healing in osteoporotic rats and enhances the osteogenic differentiation of osteoporotic BMSCs by dysregulating the AKT/NFATc1 signaling pathway.

A case report of multi-ligaments injury of the ACL-MCL-PT combined with an occult fracture of the posterolateral tibial plateau.

The anterior cruciate ligament and medial collateral ligament are important static stabilizers of the knee. The patellar tendon is part of the knee extensor mechanism. The injury simultaneously involving these three structures is very rare. This paper reports a case with simultaneous ipsilateral rupture of the anterior cruciate ligament, medial collateral ligament, patellar tendon, and an occult compression fracture of the posterolateral tibial plateau. This injury pattern has not been reported in literature yet. The injury mechanism was hypothesized as a sudden anterior translation and valgus of the proximal tibia when the knee was in high flexion, followed by an eccentric quadriceps' contracture. In the followed management, ruptured medial collateral ligament and patellar tendon were sutured with augment, while the torn anterior cruciate ligament and fracture were treated conservatively. The outcome of the treatment was satisfactory, and no complication was observed. To this combined injury, a comprehensive consideration, including physical examination, multiple imaging examinations, and analysis of injury mechanism, is essential for a full diagnosis and treatment decision. Especially, computed tomography may help to identify an occult or non-displaced fracture, which would be easily misdiagnosed when nothing unusual was found in routine X-rays. In the treatment, it is suggested to perform a selective or step-by-step repair to the damaged structures, rather than an immediate total repair after injury.

Arthroscopic Anterior Cruciate Ligament Injury in Clinical Treatment of Joint Complications and CT Observation.

Arthroscopy is the gold standard for diagnosing ACL injuries. It is a dual clinical technique for examination and treatment, which can effectively target the injury site for repair and treatment and can also accurately identify the lesion site and determine the degree of ligament injury through visual and three-dimensional observation of ligament injuries that are difficult to detect on imaging. However, this technique is invasive, so the clinic still needs to improve the related auxiliary imaging examination. In this paper, we performed MPR and VRT on patients with ACL injury and postprocessed the data. The diagnostic compliance rate of dual-source CT was 91.67% (33/36), the true positive rate was 93.33% (28/30), the missed rate was 6.67% (2/30), the true negative rate was 83.33% (5/6), and the misdiagnosis rate was 83.33% (5/6). The rate of true negative was 83.33% (5/6), and the rate of false diagnosis was 16.67% (1/6). Kappa analysis of the consistency between dual-source CT and arthroscopy showed a Kappa value of 0.719, indicating a high degree of consistency between the two examinations. In conclusion, MPR and VRT images are of clinical value for the diagnosis of ACL injury. In addition, dual-source CT can measure the CT value of the ACL and the thickness of each segment by MPR and VRT postprocessing techniques to diagnose the ligament injury in an objective, quantitative, and noninvasive way and can use dual-energy staining techniques to predict the ligament injury in a more intuitive way, which is not available in some arthroscopes.

Novel Rim Plating Technique for Treatment of the Inferior Pole Fracture of the Patella.

To aim of the present paper was to introduce a novel fixation technique for the treatment of inferior pole fracture of the patella. We performed a prospective observational study of consecutive cases of inferior pole fracture of the patella that were treated at our institution between January 2018 and June 2019. The patients include three men and one woman, with an average age of 47 years (range: 42-59 years). All patients were treated with the novel rim plating fixation technique for preserving the inferior pole of the patella. During the surgery, a 2.4 mm straight locking compression plate was contoured to adapt to the arc of the lower half of the patella as the rim plate. After reduction of the fracture, the rim plate was fixed to the proximal fragment of the patella through multiple locking screws, against the continuous pull of the patellar tendon. The rim plate encircles and constricts the inferior pole fragments, functioning as a compression and blocking construct. If necessary, an additional anterior tension band or mini locking plate can be used to further prevent anterior displacement of the inferior pole fragments. Under this rigid fixation, motion of the knee and full weight-bearing were encouraged postoperatively. The patients were followed up monthly until 12 months after surgery. The time to achieve 90°pain-free, full range of motion of the knee, and fracture healing, were recorded. Related complications were monitored, including infection, loss of reduction, fixation failure, anterior knee pain, and soft-tissue irritation. The modified Cincinnati knee rating system was used for knee function assessment. The average operative time was 58.8 min (range: 52-63 min). The average blood loss was 59.8 mL (range: 45-71 mL). For all patients, pain-free 90° range of motion was restored in 2-4 weeks, and the full range of motion was restored in 8-11 weeks. All patients achieved bone union in 6-9 weeks with no displacement of the fragments or breakage of the implant. No patient complained of anterior knee pain or soft-tissue irritation. The modified Cincinnati score at 12-month follow up demonstrated excellent outcomes in all four patients. The rim plating technique may be a feasible option for the treatment of the inferior pole fracture of the patella.

Neuropilin and tolloid-like 2 regulates the progression of osteosarcoma.

Neuropilin and tolloid-like 2 (NETO2) is aberrantly expressed in various malignancies. However, its role in osteosarcoma (OS) remains to be elucidated. This study aimed to identify the function of NETO2 in OS cells. The expression of NETO2 in sarcoma tissues was determined using the GEPIA database, and the mRNA and protein expression of NETO2 in OS cells and OS tissue was also assessed. The biological effects of NETO2 on OS cells were determined by overexpressing and downregulating NETO2. Cell proliferation, invasion, migration, colony formation, and epithelial-mesenchymal transition in OS cells were evaluated. Consistent with the GEPIA database, expression of NETO2 was upregulated in human OS samples and cell lines. NETO2 overexpression not only promoted the proliferation, colony formation, invasion, and epithelial-mesenchymal transition of OS cells, but also activated the PI3K/AKT signaling. NETO2 downregulation resulted in opposite effects. Furthermore, after using an AKT inhibitor, the effects of NETO2 on OS cells were attenuated. In conclusion, this study showed that NETO2 functions as an oncogene of osteosarcomas by activating the PI3K/AKT pathway.

Radiosensitizing effects of c­myc gene knockdown­induced G2/M phase arrest by intrinsic stimuli via the mitochondrial signaling pathway.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents and its long­term survival rate has stagnated in the past decades. Previous studies have shown that tumors in the G2/M phase are more sensitive to radiotherapy. The proto­oncogene c­myc is a transformed member of the myc family and c­myc­interacting zinc finger protein­1 (Miz­1) is a poly­Cys2His2 zinc finger (ZF) activator of cell cycle regulator genes, such as the cyclin­dependent kinase inhibitor p21. C­myc can repress the expression of p21 by binding to Miz­1 and abolishing the interaction between Miz­1 and its co­activators, which induces G2/M phase arrest. Therefore, the present study investigated the radiosensitizing effects of the c­myc gene and the sensitizing apoptosis pathway, aiming to identify a more effective combination radiotherapy treatment for osteosarcoma. The present study demonstrated that the c­myc gene was overexpressed in osteosarcoma cells compared to osteoblasts. Following inhibition of c­myc gene expression in osteosarcoma cells, tumor proliferation was significantly hindered after inducing G2/M phase arrest via regulating G2/M phase­associated proteins. Additionally, it was revealed that inhibiting c­myc gene expression combined with radiotherapy could significantly increase the apoptosis rate of osteosarcoma cells via the mitochondrial signaling pathway. In summary, the present study verified the radiosensitizing effects of c­myc gene knockdown­induced G2/M phase arrest, which was achieved by intrinsic stimuli through the mitochondrial signaling pathway.

Loss of Reduction after Cephalomedullary Nail Fixation of Intertrochanteric Femoral Fracture: A Brief Report.

OBJECTIVE: At present, cephalomedullary nail is the most frequently used implant in the management of intertrochanteric fractures around the world. The implant design and fixation techniques of the cephalomedullary nail have been continuously improved to ensure uncomplicated bone union during the past decade. However, a degree of reduction loss during bone healing is still not rare in clinical work. Many attributed this complication to misoperation during the surgery and hold that a series of techniques and tips could help to avoid the loss of reduction. However, until now there has been no research to explore whether the reduction loss after the operation can be fully prevented in the best cases. The purposes of the study are as follows: (i) to evaluate the efficiency of the current established CMN techniques; (ii) to quantify the loss of reduction under an appropriately implanted CMN to anatomically realigned intertrochanteric fractures; and (iii) to explore the possible underlying causes for the inevitable loss of reduction. METHODS: In the retrospective study, 163 consecutive cases with the intertrochanteric fractures fixed with standard cephalomedullary nail technique were reviewed. The anatomical reduction and optimal positioning of the nail were confirmed by postoperative imaging. The fracture types ranged from 31-A1.1-2.3 according to the OTA/AO fracture classification. One hundred and fifteen cases with stable fracture types (31A1.1-2.1) were allocated to Group A, and 48 cases with unstable 31A2.2-2.3 fracture types were allocated to Group B. The radiological measurements included femoral neck shortening, loss of the neck-shaft angle, cutout, and cut-through of the blade. The outcomes between postoperative and 1 year after the operation were evaluated and compared. RESULTS: The patients consisted of 66 males and 97 females with an average age of 69.4 (range: 46-78, SD: 14.6) years. At the 1-year follow-up, no fixation failure or nonunion was observed in each group. The mean femoral neck shortening and loss of the neck-shaft angle were 4.47 mm (range: 0.43-17.68, SD: 3.71) and 5.4° (range: 0.51-19.10, SD: 3.58) separately. The mean cutout and cut-through were 1.84 mm (range: 0.24-11.30, SD: 2.33) and 1.25 mm (range: 0.51-10.29, SD: 1.74). The average femoral neck shortening and loss of the neck-shaft angle were higher in Group B than Group A. Among the 23 cases with the femoral neck shortening more than 10 mm, 19 cases (16.5%) were from Group A and four cases (8.3%) were from Group B. There were nine (7.8%) cases with the loss of the neck-shaft angle more than 10° in Group A and six (12.5%) cases in Group B. CONCLUSIONS: Current established CMN techniques are efficient in treating intertrochanteric femoral fracture. However, even with currently consensual techniques of cephalomedullary nail, the process of fracture healing still risks the loss of reduction, although the migration of the blade could be minimized. This situation may associate with the intrinsic design of the CMN and further improvement is still needed.

Giant Cell Tumor of Tendon Sheath with Tarsal Bones and Intertarsal Joint Invasion: A Case Report.

The giant cell tumor of tendon sheath (GCTTS) is a benign lesion most commonly attached to the tendons and bones of the fingers, hands, and wrists. The involvement of GCTTS to the foot is uncommon. The GCTTS invading tarsal bones and intertarsal joints is not described yet, and the appropriate diagnosis and treatment remain unclear. We report a case of GCTTS with the involvement of tarsal bones and intertarsal joint. Computed tomography scan and magnetic resonance imaging were used to further diagnose and evaluate the quality and range of tumor. The patient was treated with surgical excision of the tumor without application of bone graft. After adequate clearance of the tumor, the patient returned to an asymptomatic walk in 3 months. No malfunction, fracture, or tumor recurrence was found in 2-years follow-up. This report includes clinical, radiologic, histologic diagnostic, and surgical challenges in an unexpected lesion and a review of the literature.