KCC2 overexpressed exosomes meditated spinal cord injury recovery in mice.

Exosomes show great potential in treating diseases of the central nervous system including spinal cord injury (SCI), still better engineered exosomes have more advantages. In this study, we purified exosomes from K+-Cl-co-transporter (KCC2) overexpressed bone marrow mesenchymal stem cells (ExoKCC2), to investigate the effect of ExoKCC2on neural differentiationin vitroand the repairing function of ExoKCC2in SCI micein vivo. Compared to bone marrow mesenchymal stem cells (BMSC)-derived exosomes (Exo), ExoKCC2could better promote neural stem cell differentiated into neurons, ameliorate the function recovery of SCI mice, and accelerate the neural regeneration at the lesion site. Altogether, engineered ExoKCC2may prove to be an advantageous strategy for SCI treatment.

Effect of the degree of displacement of the third fragment on healing of femoral shaft fracture treated by intramedullary nailing.

OBJECTIVE: To investigate the effect of the degree of displacement of a femoral shaft fracture with the third fragment on fracture healing after intramedullary nailing. METHODS: In total, 216 patients with closed comminuted femoral fracture admitted to Lianyungang Hospital affiliated to Xuzhou Medical University from February 2010 to February 2016 were analyzed retrospectively. Among these patients, 142 were males and 74 were females, the mean age was 38 years (range 17-64 years), and 95 cases were on the right, while 121 cases were on the left. All patients were treated with a femoral interlocking intramedullary nail. Referring to the femoral shaft diameter, the degree of displacement of the third fragment was classified into four grades: grade I (displacement was less than a third of the diameter of the shaft): 121 cases; grade II (greater than a third of the diameter and less than two thirds): 52 cases; grade III (greater than two thirds of the diameter): 28 cases; and grade IV (fracture fragment turnover): 15 cases. According to the modified Radiological Union Scale for Femur (mRUSF), the fracture union rate and the mean union time of the fracture, the effect of the degree of displacement of the third fragment on fracture healing was evaluated. RESULTS: In total, 216 patients with a mean follow-up of 15.9 months (range 6-31 months) met the inclusion criteria. The best fracture healing was the grade I displacement, with a union rate of 89.2% and a mean union time of 7.7 months. The poorest fracture healing was for the grade IV displacement, with a union rate of 13.3% and a mean union time of 16.5 months. The healing was moderate in the grade II and III displacements, with a union rate of 46.2% and 28.6%, respectively, and a mean union time of 8.6 months and 13.5 months, respectively (P < 0.05). CONCLUSIONS: The third fragment with grade I displacement requires no intervention, whereas fractures with grade IV displacement should be reduced to as near as possible to the diaphyseal bone defect to avoid nonunion. The third fragments with the grade II or III displacement should be treated with closed reduction whenever possible to achieve a displacement within the range of grade I to minimize the incidence of nonunion.

Hydroxysafflor Yellow A (HSYA) Protects Endplate Chondrocytes Against IL-1ß-Induced Injury Through Promoting Autophagy.

Background: Intervertebral disc degeneration (IDD) refers to intractable pain in patients' waist and legs, which is caused by internal structural disorder and degeneration of intervertebral. This disease severely affects the quality-of-life of people. It has been reported that hydroxysafflor yellow A (HSYA), the active ingredient in safflower extract, could inhibit IL-1ß-induced apoptosis of endplate chondrocytes. However, the mechanism by which HSYA regulates the occurrence and progression of IDD remains unclear. Methods: Rat endplate chondrocytes were isolated from the intervertebral disc. Next, toluidine blue staining and collagen II immunofluorescence staining were used to identify endplate chondrocytes. Then, MDC staining was used to detect the autophagy of endplate chondrocytes. In addition, Western blot was used to measure the expression of cleaved caspase 3, LC-3I/II and ATG7 in endplate chondrocytes. Results: IL-1ß obviously inhibited the viability and proliferation of endplate chondrocytes, while these phenomena were notably reversed by HSYA. Additionally, HSYA was able to inhibit IL-1ß-induced apoptosis of endplate chondrocytes. Moreover, HSYA protected endplate chondrocytes against IL-1ß-induced inflammation via inducing autophagy. Conclusion: HSYA protected rat endplate chondrocytes against IL-1ß-induced injury via promoting autophagy. Therefore, the present study might provide some theoretical basis for exploring novel and effective methods for patients with IDD.

Role of lncRNA PART1 in intervertebral disc degeneration and associated underlying mechanism.

Intervertebral disc degeneration (IDD) is a chronic skeletal muscle degeneration disease. Previous studies have demonstrated that long non-coding RNAs (lncRNAs) exert significant roles in serious illnesses. Prostate androgen-regulated transcript 1 (PART1) is an identified lncRNA that has been reported to be a regulator in a number of diseases. However, the potential effects of PART1 in IDD have yet to be fully elucidated. The present study aimed to investigate the roles of lncRNA PART1 in IDD and identify a possible underlying mechanism. Human nucleus pulposus (NP) cells were first exposed to lipopolysaccharide (LPS) to construct in vitro IDD models. Reverse transcription-quantitative PCR (RT-qPCR) was performed to measure lncRNA PART1 expression levels in 10 ng/ml LPS-stimulated NP cells and normal cells (untreated cells). Dual-luciferase reporter assays were conducted to verify the possible binding sites of microRNA (miR)-190a-3p on lncRNA PART1. In addition, NP cell viability and apoptosis were measured by performing MTT and flow cytometry, respectively. Expression and secretion of inflammatory factors (TNF-α, IL-1ß and IL-6) and extracellular matrix (ECM) degradation-related proteins (aggrecan and collagen type II) were measured using ELISA, RT-qPCR and western blotting. Expression levels of lncRNA PART1 in LPS-treated NP cells were found to be higher compared with those in the control groups. miR-190a-3p directly targeted lncRNA PART1. PART1 knockdown enhanced cell viability, reduced cell apoptosis, inhibited inflammatory factor secretion and promoted ECM degradation in LPS-stimulated NP cells. However, transfection with the miR-190a-3p inhibitor reversed the aforementioned PART1 knockdown-induced alterations in cell viability, apoptosis, inflammatory cytokine and ECM degradation. Collectively, these results suggest that PART1 accelerates the progression of IDD by directly targeting miR-190a-3p, which provides a novel target for IDD diagnosis and treatment.

MicroRNA-204-GSDMD interaction regulates pyroptosis of fibroblast-like synoviocytes in ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis (AS) is a disease characterized by inflammation of the sacroiliac joint and the attachment point of the spine. This study aimed to investigate the effect of microRNA (miR)-204-targeted GSDMD on fibroblast-like synoviocytes (FLSs) in AS. METHODS: miR-204, GSDMD, pyrolysis-related genes (Caspase-1, Caspase-11 and NLRP3) in synovial tissues from AS patients were tested by RT-qPCR. Online website prediction and dual luciferase reporter gene assay were conducted to verify the binding relationship between miR-204 and GSDMD. FLSs were isolated from AS patients and transfected with miR-204- or GSDMD-related oligonucleotides, siRNA and plasmids to explore their roles in pyroptosis of FLSs. Intracellular [Ca2+] was detected by laser scanning confocal microscopy, reactive oxygen species (ROS) by DCFH-DA and pyrolysis by AO/EB staining and flow cytometry. RESULTS: Decreased miR-204 and elevated GSDMD were found in synovial tissue of patients with AS. miR-204 could directly target GSDMD and inhibit GSDMD protein expression. FLSs treated with miR-204 mimic inhibited the pyroptosis rate and Caspase-1/PI double-positive cells and reduced [Ca2+], ROS, NLRP3, Caspase-1 and Caspase-11 levels in FLSs. Up-regulating GSDMD blocked the effect of miR-204 overexpression on FLSs. CONCLUSION: Altogether, up-regulated miR-204 suppresses pyroptosis of FLSs in AS via suppressing GSDMD, which may help us to understand the mechanism of AS deeply.

Effects of surgical approaches and morphological characteristics on the follow up outcomes of patients with posterolateral tibial plateau fractures.

This study aimed to study the effects of surgical approaches and identify the morphological characteristics associated with the 1-year follow-up outcome of patients with posterolateral tibial plateau fractures after successful surgery.We followed 200 postoperative patients for 1 year. The modified Hospital for Special Knee Surgery score (HSS score) was used to evaluate the functional recovery of the knee. We supposed 4 morphological characteristics in CT images acting as possible risk factors, including the anteroposterior diameters of posterolateral broken bone fragments (fragment-diameter), the damage to the posterolateral cortex of the tibial head (cortex-damage), the combinational fracture of the proximal fibula (fibula-fracture) or fracture of the medial tibial condyle (medial-condyle-fracture). Multivariate regression models were used to analyze the effect of these factors on the HSS score after adjusting the 2 surgical approaches and other confounders.The average HSS score was 85.1 ±â€Š5.8 for all the patients. We treated 155 patients with the anterolateral approach and 45 patients with the posterolateral approach. The surgical approach, fragment-diameter, fibula-fracture, and medial-condyle-fracture were correlated with the HSS scores (P < .05). After adjusting for the above factors, the Schatzker type, age and gender, compared with anterolateral approach, the posterolateral approach could improve the HSS scores by an average of 3.7 points. The fragment-diameter <20 mm and posterolateral approach interacted on the HSS scores. Comparing posterolateral and anterolateral approaches, we found that the HSS scores of patients with fragment-diameter <20 mm increased by 6.1 points (95% CI: 4.1-8.2) in the posterolateral approach, while those with fragment-diameter ≥20 mm did not significantly improve the HSS scores.The surgical approach, fragment-diameter, fibula-fracture, and medial-condyle-fracture were independent risk factors associated with the follow-up outcome of patients with posterolateral tibial plateau fractures after successful surgery. The posterolateral approach could significantly improve the HSS score in the studied hospital.

Intramedullary nail versus plate treatments for distal tibial fractures: a meta-analysis.

INTRODUCTION: Controversy remained on whether the optimal treatment for distal tibial fractures is intramedullary nail (IMN) or plate. METHODS: Databases including PubMed, Embase, Cochrane library, Wanfang and CNKI were retrieved up to May 31, 2014 for eligible studies. Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used to evaluate literature qualities. Q and I(2) test were applied to estimate heterogeneities. Moreover, subgroup analyses were performed and publication bias was detected. Mean difference (MD) and relative risk (RR), with their corresponding 95% confidence interval (CI) were used to calculate the pooled results. RESULTS: Sixteen studies were included involving 1140 participants (IMN: 599; plate: 541). There were no significant differences between IMN and plate treatments in operation time (OT), hospital time (HT), union time (UT), and incidence of deep infection (DI) and union complications (UC). However, IMN achieved a significant lower superficial infection (SI) incidence (RR, 0.41; 95% CI, 0.23 to 0.71; P = 0.001) and a significant higher malunion incidence (RR, 2.27; 95% CI, 1.56 to 3.31; P < 0.001). In subgroup analyses, IMN had significant shorter OT than plate in randomized controlled trials (RCTs) (MD, -19.04; 95% CI, -24.86 to -13.21; P < 0.0001), but comparable incidence of SI to plate in non-Asia countries. No obvious publication bias was indicated in UT and malunion. CONCLUSION: For distal tibial fractures treatment, IMN might be advantageous over plate with lower SI incidence, and comparable UT, OT and HT. Meanwhile, IMN was related to higher risk of malunion. However, more RCTs are warranted.