Comparison of proprioception recovery following anterior cruciate ligament reconstruction using an artificial graft versus an autograft.

BACKGROUND: To compare proprioception recovery after anterior cruciate ligament reconstruction (ACLR) with a hamstring tendon autograft versus the artificial Ligament Advanced Reinforcement System (LARS). MATERIAL AND METHODS: Forty patients (9 females, 31 males) with anterior cruciate ligament (ACL) rupture were enrolled in this prospective study. Patients were randomized to two groups, 1) ACLR using a hamstring tendon autograft (n = 20) or 2) ACLR using artificial LARS (n = 20). Proprioception was assessed with knee joint position sense (JPS) passive-passive test at 45° and 75° flexions, with the contralateral healthy knee as a control baseline to calculate the JPS error. Knee JPS absolute error was used as the main outcome variable and defined as the absolute difference between the reproduction and target angles. RESULTS: JPS error in both groups at 3 months after ACLR was significantly higher than that at 12 months. However, no significant difference in JPS error was detected between the LARS and autograft groups at either 3 or 12 months after ACLR. Analyzing JPS data by grouping patients according to whether ACLR was performed more or less than 1 year following injury regardless of graft type showed a statistically significant difference between the groups at 3 months, but not at 12 months, after ACLR. Patients receiving the graft within 1 year of injury had a lower JPS error than those receiving the graft more than 1 year after injury at 3 months. No complications were associated with either ACLR method. CONCLUSION: ACLR with a hamstring tendon autograft or LARS artificial graft is similarly safe and effective for recovering knee proprioception.

Orthopedic therapeutic surgery for bone metastasis of liver cancer: Clinical efficacy and prognostic factors.

Objectives: In this study, the objectives were to investigate the clinical efficacy of orthopedic therapeutic surgery (OTS) in patients with bone metastasis of liver cancer and explore the prognostic factors. Methods: The electronic medical records of patients with bone metastasis of liver cancer in the Third Affiliated Hospital of Naval Medical University from September 2016 to August 2021 were retrospectively collected. A total of 53 patients were included. Patients were assigned to the OTS (n = 35) or the control group (n = 18) based on receiving orthopedic therapeutic surgery or conservative treatment. The pre/posttreatment Karnofsky Performance Status scale (KPS) and numeric rating scale (NRS) scores were compared. Univariate and multivariate Cox regression analyses were used to explore the prognostic factors affecting survival after bone metastasis. Logistic regression analyses were adopted to discover potential factors that contributed to greater KPS score improvement. Results: The axial bone accounted for 69.8% of all bone metastases. The proportion of multiple bone metastases was 52.8%. After surgery, the median KPS score of the OTS group increased from 60 to 80 (p < 0.001), and the median increase in the OTS group was higher than that of the control group (p = 0.033). The median NRS score of the OTS group declined from 6 to 2 after surgery (p < 0.001), and the median decline in the OTS group was higher (p = 0.001). The median survival was 10 months in the OTS group vs. 6 months in the control group (p < 0.001). Higher pretreatment KPS scores, undergoing liver primary lesion surgery, and undergoing orthopedic therapeutic surgery were protective factors of survival. Undergoing orthopedic therapeutic surgery greatly improved the KPS score. Conclusions: Orthopedic therapeutic surgery for bone metastasis of liver cancer provides benefits to the quality of life. Patients who have their primary liver lesions removed, undergo orthopedic therapeutic surgery, and have a better physical condition before treatment tend to have longer survival.

3D-printed hemipelvic prosthesis combined with a dual mobility bearing in patients with primary malignant neoplasm involving the acetabulum: clinical outcomes and finite element analysis.

BACKGROUND: Limb salvage reconstruction for pelvic tumors, especially periacetabular tumors, is challenging. We combined the use of dual mobility bearing and 3D-printed hemipelvic prosthesis to improve function and reduce the probability of complications after hemi-pelvic resection in patients with primary acetabular malignancy. The purpose of this study was to evaluate the efficacy and safety of this combination. METHODS: Between October 2011 and May 2021, 11 patients with malignancies involving the acetabulum received hemipelvic replacement with a 3D-printed prosthesis and dual mobility bearing. Follow-up of postoperative survival, complications, and Musculoskeletal Tumor Society 93 (MSTS-93) lower limb functional scores were carried out. A finite element model of the postoperative pelvis was developed and input into the finite element analysis software. The Von Mises equivalent stress formula was used to analyze the stress distribution of each part of the pelvis under one gait cycle and the stress distribution at different angles of the hip joint. RESULTS: By the last follow-up, 9 of the 11 patients (81.8%) were still alive, and 2 patients had local tumor recurrence. The complications including 1 deep infection and 1 dislocation of the artificial joint. Excluding 1 amputation patient, the average score of the remaining 8 patients at the last follow-up was 21.4/30 (71.3%) on the MSTS-93. In the reconstructed pelvis, stress distributions were concentrated on the junction between hemipelvic prosthesis and screw and iliac bone on the resected side, and between femoral prosthesis stem and femoral bulb, while the stress of polyethylene lining was small. Before impact, the polyethylene lining will rotate at a small angle, about 3°. The inner stress of polyethylene liner is greater than the outer stress in all conditions. The polyethylene liner has no tendency to slide out. CONCLUSION: Pelvic tumor resection and reconstruction using 3D-printed hemipelvic prosthesis combined with dual mobility bearing was an effective treatment for pelvic tumors. Our patients achieved good early postoperative efficacy and functional recovery. The dual mobility bearing is beneficial to prevent dislocation, and the mechanical distribution and wear of the prosthesis are acceptable.

Bone Marrow Mesenchymal Stem Cell Exosome Attenuates Inflammasome-Related Pyroptosis via Delivering circ_003564 to Improve the Recovery of Spinal Cord Injury.

Bone marrow mesenchymal stem cell (BMSC) is previously reported to present a certain effect on treating spinal cord injury (SCI), while the underlying mechanism is largely uncovered. Therefore, the current study aimed to investigate the involvement of exosome-delivered circRNA profile in the BMSC's effect on pyroptosis for SCI treatment. H2O2 treated rat primary neurons were cultured with normal medium, BMSC, BMSC plus GW4869, and BMSC-derived exosome, respectively, then inflammasome-related pyroptosis markers, and circRNA profiles were detected. Subsequently, circ_003564-knockdown BMSC exosome was transfected into H2O2 treated rat primary neurons and NGF-stimulated PC-12 cells. Furthermore, in vivo validation was conducted. BMSC and BMSC-derived exosome both decreased inflammasome-related pyroptosis markers including cleaved caspase-1, GSDMD, NLRP3, IL-1ß, and IL-18 in H2O2-treated neurons, while exosome-free BMSC (BMSC plus GW4869) did not obviously reduce these factors. Microarray assay revealed that BMSC (vs. exosome-free BMSC) and BMSC-derived exosome (vs. normal medium) greatly regulated circRNA profiles, which were enriched in neuroinflammation pathways (such as neurotrophin, apoptosis, and TNF). Among three functional candidate circRNAs (circ_015525, circ_008876, and circ_003564), circ_003564 was most effective to regulate inflammasome-related pyroptosis. Interestingly, circ_003564-knockdown BMSC exosome showed higher expression of inflammasome-related pyroptosis markers compared to negative-control-knockdown BMSC exosome in H2O2 treated primary neurons/NGF-stimulated PC-12 cells. In vivo, BMSC exosome improved the function recovery and decreased tissue injury and inflammasome-related pyroptosis in SCI rats, whose effect was attenuated by circ_003564 knockdown transfection. BMSC exosome attenuates inflammasome-related pyroptosis via delivering circ_003564, contributing to its treatment efficacy for SCI.

Novel Nomograms as Aids for Predicting Recurrence and Survival in Chordoma Patients: A Retrospective Multicenter Study in mainland China.

STUDY DESIGN: A retrospective data analysis was performed. OBJECTIVE: The aim of this study is to explore the significant prognostic factors and propose new nomograms to facilitate clinical decision-making. SUMMARY OF BACKGROUND DATA: Chordoma is a rare bone tumor. The clinical features and optimal therapeutic strategies are still uncertain. METHODS: Chordoma patients treated in four medical centers of mainland China before January 2015 were included. The predictors for local relapse-free survival (LRFS) and overall survival (OS) were identified by the Lasso regression and Cox proportional hazards regression model. Then the nomograms were developed. Their discrimination, calibration, and accuracy were evaluated by the C-index, calibration curve, and receiver operating characteristic curve (ROC), respectively. RESULTS: A total of 341 patients were identified and full prognostic variable data were available for 276 patients. A total of 179 patients (64.9%) experienced recurrence and 122 patients (44.2%) died of all causes with a median follow-up time of 57.5 (range, 1-325) months. We identified recurrence-relevant factors of tumor size, tumor location, histology subtype and resection method, and death-relevant factors of tumor size, tumor location, resection method, complication, and postoperative recurrence. The constructed LRFS and OS nomograms showed good calibration and discriminative ability (C index 0.79 and 0.76, respectively). The ROCs suggested decent prediction ability with the 5-year area under curve (AUC) value of 0.868 and 0.786, respectively. CONCLUSION: Based on the multicenter case series of chordoma with a relative long follow-up, we proposed two nomograms to predict the prognosis on the basis of recurrence- and death-relevant factors. These findings could be referenced in the clinical decision-making process and provide additional prognostic information for risk stratification. LEVEL OF EVIDENCE: 4.

Long intergenic non-coding RNA 511 correlates with improved prognosis, and hinders osteosarcoma progression both in vitro and in vivo.

BACKGROUND: This study aimed to investigate the correlation of long intergenic non-coding RNA 511 (LINC00511) with clinicopathological characteristics and overall survival (OS) in osteosarcoma patients and to explore its function in osteosarcoma in vitro and in vivo. METHODS: Tumor tissues and adjacent tissues from 45 osteosarcoma patients were acquired, and LINC00511 expression was detected. In vitro, LINC00511 expression was detected in osteosarcoma cell lines and osteoblast cell line. LINC00511 overexpression-treated (OE-LINC00511) and nonsense overexpression-treated (OE-control) MG-63 and Saos-2 cells were cultured, followed by the assessment of cell proliferation, apoptosis, migration, and invasion. In vivo, tumor weight and volume were measured in OE-LINC00511 and OE-control xenografted mice. RESULTS: LINC00511 expression was decreased in tumor tissues compared with adjacent tissues (P < .001), and its high expression correlated with increased tumor cell necrosis rate to neoadjuvant chemotherapy (P = .025) and prolonged OS (P = .010). In vitro, LINC00511 expression was decreased in osteosarcoma cell lines (including MG-63, U-2OS, Saos-2, and HOS) compared with osteoblast cell line (All P < .001). Cell proliferation was decreased at 48 hours (Both P < .01) and 72 hours (Both P < .001) (in MG-63 and Saos-2 cells); cell apoptosis was increased (P < .05) (in Saos-2 cells); cell migration and invasion were decreased (All P < .01) (in MG-63 cells and Saos-2 cells) in OE-LINC00511 compared with OE-control. In vivo, tumor volume was reduced at week 4 (P < .001), week 5 (P < .001), week 6 (P < .001) in OE-LINC00511 compared with OE-control. Tumor weight was declined in OE-LINC00511 than OE-control (P < .001). CONCLUSIONS: LINC00511 acts as a potential biomarker and therapeutic option for osteosarcoma.

Application of assisted portal under anterior horn of lateral meniscus for the treatment of discoid meniscus injury.

PURPOSE: The assisted inferior anterolateral portal under anterior horn of the lateral meniscus (UAHLM portal) was applied to treat the lateral discoid meniscus injury conveniently and the clinical outcomes were evaluated. METHODS: A retrospective review was conducted on 60 patients who underwent arthroscopic surgery with a symptomatic discoid lateral meniscus. Normal anterolateral/anteromedial portals assisted with UAHLM portal (1-2 cm inferior to the anterolateral portal) were used. All patients were followed up for 24-48 months (median, 33 months) and evaluated by MRI images and clinical outcomes including clinical findings, Lysholm scores and IKDC scores. RESULTS: After meniscus plasty with or without repair, most of the upper layer of lateral meniscuses was retained. A total of 54 patients (16 males and 38 females, 42 ±â€¯17.8 years old) showed satisfactory clinical results without requiring reoperation after a median follow-up time of 33 months. At final follow-up, a full range of motion was achieved in all patients. MRI indicated the thickness of anterior horn of lateral meniscus was (5.38 ±â€¯1.09 mm) before the operation and (4.04 ±â€¯0.71 mm) after the operation at the 2-year follow-up; clinical outcomes were improved significantly than the baseline: positive McMurray test (50 vs. 2, P< 0.001), Lysholm score (64.9 ±â€¯9.0 vs. 94.7 ±â€¯4.9, P< 0.001), and IKDC score (54.4 ±â€¯7.7 vs. 92.6 ±â€¯4.3, P< 0.001). No significant complication was observed during the follow-up. CONCLUSION: Thus, this technique with assisted UAHLM portal was convenient for arthroscopic discoid meniscus plasty and meniscus repair and served as an effective method in patients with a symptomatic discoid lateral.

Sodium hydrosulfide mitigates dexamethasone-induced osteoblast dysfunction by interfering with mitochondrial function.

Osteoporosis is one of the clinical complications of long-term treatment with glucocorticoids (GCs), characterized by systemic damage of bone mass and osteoblast dysfunction. Hydrogen sulfide was found to be involved in GCs-induced osteoblast dysfunction. Osteoblastic MC3T3-E1 cell and mitochondrial function were determined by cell viability, M-CSF level, and ALP activity and superoxide production, membrane potential, and ATP level, respectively. The purpose of this research was to explore the impact of NaHS on osteoblastic MC3T3-E1 cell function as well as on Sirt1 and PGC1α expression in dexamethasone (DEX)-treated osteoblast cells. DEX-treated MC3T3-E1 cells exhibited decreased cell viability and ALP activity, as well as increased M-CSF level; all these changes were dramatically attenuated by NaHS. DEX-treated cells also displayed mitochondrial dysfunction, namely decreased mitochondrial membrane potential and ATP generation and increased superoxide generation, which were partly reversed by NaHS. We confirmed decreased Sirt1 and PGC1α protein expression in DEX-treated MC3T3-E1 cells by Western blot, which was also partly reversed by NaHS. Silencing of Sirt1 abrogated the protective effect of NaHS against DEX-induced cell damage and mitochondrial dysfunction. NaHS alleviates DEX-induced osteoblastic MC3T3-E1 cell injury by improving mitochondrial function.

Up-regulated expression of CD147 gene in malignant bone tumor and the possible induction mechanism during osteoclast formation.

It is increasingly evident that the microenvironment of bone can influence cancer phenotype in many ways that favor growth in bone. CD147, a transmembrane protein of the immunoglobulin (Ig) superfamily, was identified independently in different species and has many designations across different species. However, expression levels of CD147 mRNA in bone cancer have not been described. In this study, we have used real-time fluorescence quantification (RT-PCR) to demonstrate CD147 expression in malignant bone cancer and benign bone tumor tissues. The results suggested that the expression of CD147 gene was significantly up-regulated in malignant bone cancer. Moreover, we found that over-expressed RANKL progressively enhanced osteoclast formation up to 48 h, which suggested that RANKL could promote the formation of osteoclast, indicating that both CD147 and RANKL play important roles in the formation of osteoclasts. Furthermore, the expressions of four osteoclast specific expression genes, including TRACP, MMP-2, MMP-9 and c-Src, were analyzed using RT-PCR. The results indicated that four osteoclast-specific expression genes were detectable in all osteoclast with different treatments. However, the highest expression level of these four osteoclast-specific expression genes appears in the CD147+ RANKL group and the lowest expression level of these four osteoclast-specific expression genes appears with si-RANKL treatment. Characterization of the role of CD147 in the development of tumors should lead to a better understanding of the changes occurring at the molecular level during the development and progression of primary human bone cancer.

Up-regulated expression of CD147 gene in malignant bone tumor and the possible induction mechanism during osteoclast formation

It is increasingly evident that the microenvironment of bone can influence cancer phenotype in many ways that favor growth in bone. CD147, a transmembrane protein of the immunoglobulin (Ig) superfamily, was identified independently in different species and has many designations across different species. However, expression levels of CD147 mRNA in bone cancer have not been described. In this study, we have used real-time fluorescence quantification (RT-PCR) to demonstrate CD147 expression in malignant bone cancer and benign bone tumor tissues. The results suggested that the expression of CD147 gene was significantly up-regulated in malignant bone cancer. Moreover, we found that over-expressed RANKL progressively enhanced osteoclast formation up to 48 h, which suggested that RANKL could promote the formation of osteoclast, indicating that both CD147 and RANKL play important roles in the formation of osteoclasts. Furthermore, the expressions of four osteoclast specific expression genes, including TRACP, MMP-2, MMP-9 and c-Src, were analyzed using RT-PCR. The results indicated that four osteoclast-specific expression genes were detectable in all osteoclast with different treatments. However, the highest expression level of these four osteoclast-specific expression genes appears in the CD147+ RANKL group and the lowest expression level of these four osteoclast-specific expression genes appears with si-RANKL treatment. Characterization of the role of CD147 in the development of tumors should lead to a better understanding of the changes occurring at the molecular level during the development and progression of primary human bone cancer.

MicroRNA-150 upregulation reduces osteosarcoma cell invasion and metastasis by downregulating Ezrin.

The present study aimed to investigate the effect of microRNA-150 (miRNA/miR-150) in osteosarcoma (OS) cell invasion and metastasis by the regulation of Ezrin. To compare the differences in the expression of miR-150 and Ezrin, cell models of OS metastasis were established by exogenous transfection of miR-150 on the basis of different expression levels of miR-150. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to estimate these expression levels. Ezrin expression was detected by western blot assay. Methylthiazolyldiphenyl-tetrazolium bromide assay was performed to determine cells proliferation. Cell invasion and migration were measured in vitro by Transwell migration assays. Detection of apoptosis adopted flow cytometry. The results of RT-qPCR showed that the miR-150 expression in OS F5M2 cells was significantly increased following exogenous transfection of miR-150 mimics, and the expression of miR-150 was positively correlated with the concentration of the miR-150 mimics. Western blot assay indicated that the Ezrin expression in the F5M2 cells was decreased with the exogenous overexpression of miR-150. Additionally, Transwell assays revealed that the overexpression of miR-150 significantly suppressed the invasion and metastasis ability of the F5M2 cells. miR-150 upregulation may reduce OS cell invasion and metastasis by downregulating the expression of Ezrin.

Effects of Wharton's jelly cells of the human umbilical cord on acute spinal cord injury in rats, and expression of interleukin-1ß and nerve growth factor in spinal cord tissues.

To study the effects of Wharton's jelly cells (WJCs) on acute spinal cord injury (SCI), 81 rats were divided into a sham surgery group, a model group, and a WJC transplantation group (n = 27). Motor functions of the model and WJC transplantation groups were partially recovered, and the recovery was better in the latter group. The WJC transplantation group had integral spinal cord tissues. Compared with the model group, the WJC transplantation group expressed significantly less interleukin-1ß (IL-1ß) and more nerve growth factor (NGF) (P < 0.05). WJC transplantation changed the microenvironment of the SCI site, inhibited IL-1ß expression, increased NGF expression, promoted the recovery of neurological function, and relieved secondary SCI.

Melatonin lowers edema after spinal cord injury.

Melatonin has been shown to diminish edema in rats. Melatonin can be used to treat spinal cord injury. This study presumed that melatonin could relieve spinal cord edema and examined how it might act. Our experiments found that melatonin (100 mg/kg, i.p.) could reduce the water content of the spinal cord, and suppress the expression of aquaporin-4 and glial fibrillary acidic protein after spinal cord injury. This suggests that the mechanism by which melatonin alleviates the damage to the spinal cord by edema might be related to the expression of aquaporin-4 and glial fibrillary acidic protein.