Search

We generated a rat model of sciatic nerve crush injury and characterized the effects of curcumin on sciatic nerve recovery by using behavioral experiments, hematoxylin-eosin staining, toluidine blue staining, and immunohistochemical. Proteomic analysis using tandem mass tagging was performed to determine differentially expressed proteins (DEPs), and GO and KEGG pathway analyses of overlapping DEPs was conducted, following which, qPCR, western blotting, and immunofluorescence were further performed to validate the proteins of interest. Finally, a Schwann cell injury model was used to verify the effect of curcumin on potential targets. The rat model was successfully established and curcumin improved the sciatic nerve function index of rats with sciatic nerve injury (SNI) and increased the number and diameter of myelinated axons in the sciatic nerve. In the Sham group versus the Injured group and in the Injured group versus the Curcumin group, we identified a total of 4,175 proteins, of which 953 were DEPs, and 218 were known overlapping DEPs. Ten associated pathways, such as calcium signaling pathway, biosynthesis of antibiotics, and long-term potentiation, were identified. The 218 overlapping DEPs were primarily involved in negative regulation of apoptotic process, biological processes, cytoplasm cellular component, and protein binding molecular function based on GO annotation. Curcumin promoted increased expression of ApoD and inhibited the expression of Cyba in vivo and in vitro. These results indicated that curcumin promoted sciatic nerve repair through regulation of various proteins, targets, and pathways. Cyba and ApoD may be potential targets of curcumin in the treatment of SNI.

The present study was developed to explore whether microRNA (miR)-760 targets heparin-binding EGF-like growth factor (HBEGF) to control cartilage extracellular matrix degradation in osteoarthritis. Both miR-760 and HBEGF expression levels were analysed in human degenerative cartilage tissues and in interleukin (IL)-1β/tumour necrosis factor (TNF)-α-treated chondrocytes in vitro. A series of knockdown and overexpression assays were then used to gauge the functional importance of miR-760 and HBEGF in OA, with qPCR and western immunoblotting analyses. Bioinformatics assays were used to identify putative miR-760 target genes, with these predictions then being validated through RNA pulldown and luciferase reporter assays. A murine anterior cruciate ligament transection model of OA was then established to prove the in vivo relevance of these findings. These experiments revealed that human degenerative cartilage tissues exhibited significant increases in miR-760 expression with a concomitant drop in HBEGF levels. IL-1β/TNF-α-treated chondrocytes also exhibited significant increases in miR-760 expression with a concomitant drop in HBEGF expression. When chondrocytes were transfected with either miR-760 inhibitor or HBEGF overexpression constructs, this was sufficient to interfere with degradation of the extracellular matrix (ECM). Moreover, miR-760 was confirmed to control chondrocyte matrix homeostasis by targeting HBEGF, and the overexpression of HBEGF partially reversed the effects of miR-760 mimic treatment on the degradation of the cartilage ECM. When OA model mice were administered an intra-articular knee injection of an adenoviral vector encoding a miR-760 mimic construct, cartilage ECM degradation was aggravated. Conversely, the overexpression of HBEGF in OA model mice partially reversed the effects of miR-760 overexpression, restoring appropriate ECM homeostasis. In summary, these data indicated that the miR-760/HBEGF axis plays a central role in orchestrating the pathogenesis of OA, making it a candidate target for therapeutic efforts in OA.

In the present study, we aimed to investigate the clinical outcomes of arthroscopic discoid lateral meniscus (DLM) plasty and the adaptive changes in the patellofemoral joint after surgery. From September 2010 to March 2012, 25 patients with DLM injuries who underwent arthroscopic meniscus plasty were enrolled in the prospective study. All patients underwent clinical evaluation before the operation and at the last follow-up, and imaging evaluation was performed by upright magnetic resonance imaging before and 1 month after the operation as well as at the last follow-up. Clinical evaluation included Lysholm score, Kujala score, McMurray's sign, patellar mobility, patella grind test, and quadriceps atrophy. Imaging evaluation included bisect offset index, patella tilt angle (PTA), and cartilage damage. Lysholm score, Kujala score, McMurray's sign, and quadriceps atrophy at the last follow-up were significantly improved compared with the preoperative levels (P .05). At the last follow-up, there were no statistical differences in patella mobility and patella grind test compared with the preoperative levels. In addition, bisect offset index and PTA showed a dynamic trend of rising and then falling over time (P .05). At 1 month after the operation, bisect offset index and PTA were significantly increased compared with the preoperative levels or the values at the last follow-up (P .05), while there were no differences between the preoperation and the last follow-up. Cartilage damage became worse with time (P0.05), and the 2 were positively correlated (Spearman = 0.368). At the last follow-up, the degree of cartilage damage was significantly increased compared with the preoperative level (P .017), while there was no significant difference between the 1-month postoperative grade and the preoperational grade or the last follow-up grade. The effect of arthroscopic DLM plasty on the patellofemoral joint was dynamic, with the position of the patella deviating in the early stages and recovering in the mid-term, especially when the knee was in the biomechanical standing position. In addition, the patellofemoral joint cartilage might undergo accelerated degeneration after the operation, while the mid-term effect of the operation was positive, and the patellofemoral joint function was acceptable.

Surface-enhanced Raman spectroscopy (SERS) substrates based on metal/semiconductors have attracted much attention due to their excellent photocatalytic activity and SERS performance. However, they generally exhibit low light utilization and photocatalytic efficiencies. Herein, molybdenum disulfide coated titanium dioxide modified with gold nanoparticles (MoS

This study aimed to compare the outcomes at the clinical and functional levels of suprapatellar (SP) and infrapatellar (IP) approaches for intramedullary nailing in treating tibial shaft fracture. Patients who underwent tibial shaft fracture intramedullary nailing by the SP approach or IP approach in a trauma center were retrospectively reviewed. The demographics, intraoperative fluoroscopy time, operation time, blood loss, irrigation volume, postoperative X-ray alignment, and complications of patients were compared between the two groups under different approaches. Lysholm knee score, visual analog score (VAS), and incidence of anterior knee pain (AKP) were assessed 1 year after surgery. The study finally included well-documented 81 patients (38 SP versus 43 IP). The SP group exhibited significantly shorter intraoperative fluoroscopy time than that of the IP group (81.7 ± 14.5 s vs. 122.0 ± 24.3 s, P 0.05). The Lysholm knee score was higher in the SP group than that of the IP group (87 ± 8 vs. 80 ± 15, P 0.05). Compared with the IP approach, the application of intramedullary nailing through the SP approach in treating tibial shaft fractures can effectively shorten the intraoperative fluoroscopy time, correct coronal plane angulation and translation deformity, reduce the incidence of AKP and improve postoperative function.

Diabetic wounds increase morbidity and decrease quality of life in patients with type 2 diabetes. Serum miR-27-3p levels are reportedly elevated in type 2 diabetic patients. In the present study, we explored the role of miR-27-3p during wound healing. We found that miR-27-3p is overexpressed in cutaneous fibroblasts of diabetic patients and mice. miR-27-3p knockdown enhanced the proliferation and migration of fibroblasts, while suppressing the incidence of fibroblast apoptosis. Overexpressing miR-27-3p in fibroblasts had the opposite effects. We also identified neuro-oncological ventral antigen 1 (NOVA1) as a target of miR-27-3p in fibroblasts. Knocking down NOVA1 using targeted siRNA mimicked the effects of miR-27-3p overexpression in fibroblasts. Administration of miR-27-3p to the area around wounds inflicted in mice delayed healing of those wounds. This suggests that miR-27-3p suppresses fibroblast function by targeting NOVA1, which results in the slowing of wound healing. These findings may offer a new approach to the treatment of diabetic wound healing.

Growing evidence has indicated that microRNAs (miRNAs) are modulators of osteoarthritis (OA) development and progression. In this study, we first evaluated the anti-apoptosis and chondroprotective effects of microRNA-675-3p (miR-675-3p) on interleukin-1β (IL-1β)-stimulated human chondrocytes. The overexpression of miR-675-3p inhibited apoptosis and cartilage matrix degradation and promoted cell proliferation in human chondrocytes. Target gene prediction and luciferase reporter assays suggested that G-protein subunit γ 5 (GNG5) may be the target gene of miR-675-3p. The overexpression of miR-675-3p inhibited IL-1β-stimulated chondrocyte apoptosis, and this effect was reversed by the overexpression of GNG5. Finally, we used bioinformatic tools and biological methods to show that the long noncoding RNA X-inactive specific transcript (lncRNA XIST) could bind to miR-675-3p, which affects the expression of GNG5 mRNA. Our findings may substantiate miR-675-3p as a new treatment for OA.

For survival and quality of human life, the search for better ways to ensure food safety is constant. However, food contaminants still threaten human health throughout the food chain. In particular, food systems are often polluted with multiple contaminants simultaneously, which can cause synergistic effects and greatly increase food toxicity. Therefore, the establishment of multiple food contaminant detection methods is significant in food safety control. The surface-enhanced Raman scattering (SERS) technique has emerged as a potent candidate for the detection of multicomponents simultaneously. The current review focuses on the SERS-based strategies in multicomponent detection, including the combination of chromatography methods, chemometrics, and microfluidic engineering with the SERS technique. Furthermore, recent applications of SERS in the detection of multiple foodborne bacteria, pesticides, veterinary drugs, food adulterants, mycotoxins and polycyclic aromatic hydrocarbons are summarized. Finally, challenges and future prospects for the SERS-based detection of multiple food contaminants are discussed to provide research orientation for further.

Rheumatoid arthritis (RA) is a systemic autoimmune disease with clinical manifestations including joint cartilage, synovitis, and bone damage. Here we developed an injectable erythrocyte gel loaded with Bulleyaconitine A (BLA) for the treatment of RA and demonstrated its anti-inflammatory effects in vivo and in vitro. In vitro experiments showed that BLA could effectively down-regulate the expression of pro-inflammatory factor in activated macrophages through the nuclear factor-κB (NF-κB) pathway. In vivo experiments have shown that the injection of BLA@RBCs in the inflammatory joints of CIA mice increases the local concentration of BLA in a long time. Improved therapeutic outcomes and reduced toxicity of BLA are demonstrated in our work. Together, the developed BLA@RBCs drug delivery system provides an alternative strategy to treat RA joints and shows high potential in clinical RA treatment.

Purpose This article reports on FLVCR-AS1 effects on osteosarcoma (OS) growth. Methods Tumor tissue and adjacent normal tissue of 48 OS patients were collected. HOS and 143B cells were transfected. Gene expression was examined with qRT-PCR and Western blot. CCK8 assays and cell cloning was performed to measure cell proliferation. Cell cycle and apoptosis were assessed. Luciferase-reporter gene assays and RNA pull-down tests were used to detect targeting relationships between genes. Results Prominently higher FLVCR-AS1 expression was found in OS tissue and cells, and was associated with poor prognosis (P

BACKGROUND Hydrogels are ideal biological carriers in vivo and have been widely used in the treatment of wound healing through loading with or without bioactive substances. Platelet-rich plasma (PRP) is purified from autologous plasma and has known curative efficacy for wound healing. The combined efficacy of shorten poly-N-acetyl glucosamine (sNAG) hydrogels and PRP in the treatment of wound healing has not been previously assessed. MATERIAL AND METHODS The cytotoxic and proliferative effects of PRP on fibroblasts were detected using Cell Counting Kit-8 assays and flow cytometry. The levels of cyclin D1 and cyclin D3 were assessed to evaluate cell proliferation. Protein expression was assessed by western blot analysis. Adenosine levels were assessed by enzyme-linked immunosorbent assay. Cell apoptosis was assessed by flow cytometry and western blot analysis. Rat wound models were performed, and the effects of PRP, single hydrogels, and sNAG hydrogels loaded with PRP were respectively detected through the assessment of wound closure. Hematoxylin eosin staining was used to measure the depth and width of regenerative scars. RESULTS Our results demonstrated that PRP promotes fibroblast proliferation and inhibits apoptosis. PRP contains abundant levels of adenosine, which has a positive role on fibroblast function, whilst the inhibition of adenosine A2A receptors impairs the efficacy of PRP. sNAG hydrogels loaded with PRP showed curative efficacy during wound healing in mice. Mice treated with hydrogels loaded with PRP showed high levels of regeneration with scarless healing. CONCLUSIONS Our results indicate that sNAG hydrogels loaded with PRP promote wound healing. The pro-proliferative, and anti-apoptotic effects of the fibroblasts are mediated by the activating A2A receptor in response to elevated adenosine levels.

Dissolved biomethane in anaerobic effluents has long been a hurdle for energy harvesting through anaerobic wastewater treatment processes. Here, we present a novel membrane process for dissolved methane recovery through the normal range of domestic wastewater temperatures by utilizing an omniphobic (nonwetting) microporous membrane. In a process driven by a solubility gradient, dissolved methane is extracted from a methane-rich aqueous solution (feed), transported across the omniphobic membrane, and absorbed into a nonpolar organic solvent (draw) that has a high solubility for methane. We fabricated the omniphobic membrane by coating a microporous polymeric membrane with silica nanoparticles, followed by surface fluorination. Using the omniphobic membrane, we demonstrate that nearly ≥90% of dissolved methane is recovered from methane-saturated feedwater at 15, 25, and 35 °C, simulating anaerobic effluents produced in the psychrophilic to mesophilic temperature range, while negligible transport of water is...

Osteoarthritis (OA), the most common form of human joint disease, is characterized by progressive degeneration of the articular cartilage, synovitis and subchondral osteoporosis. Chondrocyte apoptosis is the primary pathogenic mechanism of OA and is considered to be a potential therapeutic target. Sulforaphane (SFN), a dietary isothiocyanate obtained from cruciferous vegetables, has been reported to exert an anti-apoptotic effect by activating sirtuin 1 (SIRT1). To the best of our knowledge, however, the effects of SFN on apoptotic responses in OA have not been reported. In the present study, SFN was shown to significantly inhibit chondrocyte apoptosis while enhancing expression levels of SIRT1 in a H2O2-induced OA mouse model. The anti-apoptotic effect of SFN was reversed by SIRT1 small interfering RNA, implying that SIRT1 exerted a protective role against the effect of SFN on chondrocytes. The expression levels of C/EBP homologous protein, 78-kDa glucose regulated protein, Bax, Bcl-2 and cleaved caspase 3 were found to be downregulated in SFN-treated mice. Furthermore, SFN ameliorated cartilage degradation in the OA mouse model. These findings indicate that SFN exerted an anti-apoptotic effect on chondrocytes and ameliorated OA in vivo by activating the SIRT1 signaling pathway.

Objective To evaluate the midterm outcomes and the capsular healing in patients who had interportal capsulotomy versus periportal capsulotomy of hip arthroscopy. Methods Retrospectively reviewed 33 patients with labral tear received hip arthroscopy, with an average age of 41 (27‐67) years, including 13 cases of Cam deformity and three cases of Pincer deformity. All patients had positive sign of flexion adduction internal rotation or flexion abduction external rotation. With MRI and radiographic (CT, X plain) imageological examination. MRI showed that all patients had labral tear. Radiographic finding (CT, X plain) showed the pathological changes of acetabular and femoral neck osteophyte. One group with 23 patients were treated with periportal capsulotomy. Another group with 10 patients were treated with interportal capsulotomy. All patients did not close the capsule. Clinical outcomes were measured with the Hip Outcome Score Activities of Daily Living (HOS‐ADL) and the modified Harris Hip Score (mHHS), patient satisfaction measured with visual analogue scale (VAS). The healing of the capsule was evaluated by MRI. MRI showed continuous capsular indicated healing, discontinuous capsular indicated unhealing. Postoperatively 6 months, mHHS and HOS‐ADL were obtained. Randomized controlled trials were used in this study for analysis. Results All patients were followed up with average time of 9.3 months(3‐29 months). The postoperative symptoms were obviously relieved, the VAS decreased from (4.9 ± 0.6) to (1.2 ± 0.2) after 3 months postoperative. Follow up 6 months post‐operation, patients in the interportal group, the mHHS and HOS‐ADL scores improvement were respectively 69.4 ± 9.3 & 70 ± 8.8 pre‐operation, and 92.5 ± 5.0 & 86.6 ± 5.4 post‐operation (P < 0.05); Patients in the periportal group, the mHHS and HOS‐ADL scores improvement were respectively 69.9 ± 15.8, 68.1 ± 15.0 pre‐operation, and 90.1 ± 9.3 & 86.7 ± 7.9 post‐operation (P < 0.05).The differences were statistically significant. Six months after operation, MRI showed that 23 patients with periportal capsulotomy, the capsule have healed, without other complications. Three of the ten patients with interportal capsulotomy were healed and seven were not. Conclusion Interportal and periportal capsulotomy had good outcomes. The technique of periportal capsulotomy had little damage to the joint capsule. Although the capsule did not close, the capsule healed well in postoperative follow‐up. The nonunion rate of the joint capsule was high in the interportal capsulotomy without close the capsule., We chose periportal capsulotomy to cut the joint capsule. Establish anterolateral portal and Mid‐anterior portal, and the capsule were not closed after operation; Six months after operation MRI showed that the joint capsule healed well.

Skeletal muscle injury is accompanied by inflammation, which is common in clinical practice. To data, there is no effective method to promote skeletal muscle regeneration. Here, we develop an ROS-scavenging hydrogels loaded with MSCs (Gel@MSCs), which offer a new strategy for modulating the local inflammatory microenvironment and improve the ability of skeletal muscle repair. The therapeutic scaffold consisting of ROS-degradable hydrogel could be injected into the injured site of skeletal muscle while MSCs contribute to new myofiber formation. We found that ROS-degradable hydrogel improved the survive and of MSCs ability of MSCs. Gel@MSCs inhibited the production of inflammatory factors by promoting polarization of M2 macrophages. In addition, it promoted the expression of genes and proteins related to myogenesis in MSCs. The ROS scavenged by hydrogels further reduced the inflammatory responses. We demonstrated that regeneration of damaged muscle tissue is achieved by local treatment of Gel@MSCs, due to the activated myogenic ability, increased M2 macrophages and reduced inflammatative environment.

Background: The optimal clinical treatment and the computed tomography (CT) morphological characteristics of posterior malleolar fractures (PMF) with talar subluxation remain inconclusive. Clinically, both plate screws and lag screws are widely used to fix posterior malleolar fragments using a direct or indirect approach. We sought to summarize the morphological characteristics and modified classification on the basis of CT and the intraoperative strategy for posterior talar subluxation in PMF. Methods: Retrospectively, 46 adult PMF patients with subluxations of the talus were recruited as the study cohort. According to its morphological features, PMF with subluxation of the talus can be divided mainly into two types using this modified classification: a complete fracture (the single-fragment type) and PMF with two-angled fracture fragments (the double-fragment type). The cohort’s demographic information, classifications, fracture morphology, fixation methods, pain levels, and functional scores were recorded for both fracture types. Results: The average values of the depths and heights of the posterior malleolar fragments were (29.1±7.3) mm for the single-fragment type and (17.9±4.2) mm for the double-fragment type. There was a significant difference in the mean values between the two types (P < 0.05). Posterior plate fixation was suitable for the single-fragment type, while antero-posterior and postero-anterior (AP-PA) lag screws fixations were made available for the double-fragment type. Both methods achieved good results. No significant differences were found in terms of sex, age, body mass index (BMI), side, Haraguchi classification, Bartoníček and Rammelt classification, Visual Analog Scale (VAS) scores, or American Orthopedic Foot & Ankle Society scores (AOFAS) when comparing the single-/double-fragment type groups after the mid-term follow-up (P > 0.05). Conclusion: According to the injury mechanism and the morphological characteristics of the fractures, the proposed improved classification system for PMF with subluxation of the talus based on the injury mechanism and the fracture morphology can provide guidance for surgical management strategies and achieve optimal outcomes.

Background and Objective: Different external skeletal fixators have been widely used in preoperative traction of high-energy tibial fractures prior to a definitive surgical treatment. However, early complications associated with this staged treatment for traction and soft tissue injury recovery have rarely been discussed. This study aimed to analyze the early complications associated with preoperative external traction fixation in the staged treatment of tibial fractures.Materials and Methods: A total of 402 patients with high-energy tibial fractures treated using preoperative external traction fixation at a level-1 trauma center from 2014 to 2018 were enrolled in this retrospective study. Data regarding the demographic information, Tscherne soft tissue injury, fracture site, entry point placement, and duration of traction were recorded. Procedure-related complications such as movement and sensation disorder, vessel injury, discharge, infection, loosening, and iatrogenic fracture were analyzed.Results: The mean patient age was 42.5 (18–71) years and the mean duration of traction was 7.5 (0–26) days. In total, 19 (4.7%) patients presented with procedure-related complications, including technique-associated complications in 6 patients and nursing-associated complications in 13. Differences in the incidence of complications with respect to sex, affected side, soft tissue injury classification, and fracture sites were not observed. However, the number of complications due to hammer insertions was significantly fewer than those due to drill insertions (2.9% vs. 7.4%).Conclusion: The application of preoperative external traction fixation had been proved to be an ideal alternative treatment for high energy tibial fractures. In this study, we found the incidence of early complications of the fixation is low, and it is not significantly associated with the severity of soft tissue injury and fracture site. Although relatively rough and more likely to cause pain, complications of hammer insertions were significantly fewer than drill insertions. The possible reason was higher probability of heat damage and loosening by drilling.

Background It is technically challenging to restore hip rotation center exactly in total hip arthroplasty (THA) for patients with end-stage osteoarthritis secondary to developmental dysplasia of the hip (DDH) due to the complicated acetabular morphology changes.In this study, we developed a new method to restore hip rotation center exactly and rapidly in THA with the assistance of three dimensional (3-D) printing technology. Methods Seventeen patients (21 hips) with end-stage osteoarthritis secondary to DDH who underwent THA were included in this study. Simulated operations were performed on 3-D printed hip models for preoperative planning. The Harris fossa and acetabular notches were recognized and restored to locate acetabular center. The agreement on the size of acetabular cup and bone defect between simulated operations and actual operations were analyzed.Clinical and radiographic outcomes were recorded and evaluated. Results The sizes of the acetabular cup of simulated operations on 3-D printing models showed a high rate of coincidence with the actual sizes in the operations(ICC value = 0.930) There was no significant difference statistically between the sizes of bone defect in simulated operations and the actual sizes of bone defect in THA( t value = 0.03,P value = 0.97). The average Harris score of the patients was improved from (38.33 ± 6.07) preoperatively to the last follow-up (88.61 ± 3.44) postoperatively.The mean vertical and horizontal distances of hip rotation center on the pelvic radiographs were restored to (15.12 ± 1.25)mm and ( 32.49 ± 2.83) mm respectively. No case presented dislocation or radiological signs of loosening until last follow-up. Conclusions The application of 3-D printing technology facilitates orthopedists to recognize the morphology of Harris fossa and acetabular notches, locate the acetabular center and restore the hip rotation center rapidly and accurately.

Purposes to study the effect of titanium particles on MLO-Y4 and the effects of osteocytes alterations on osteoblasts. Methods cultured MLO-Y4 osteocytes were exposed to different concentrations of titanium (Ti) particles, cell viability was measured using the Cell Counting Kit-8 (CCK-8) assay, apoptosis of MLO-Y4 cells was evaluated by flow cytometry, Real-time PCR quantification of mRNA expression of SOST, at the same time with Western Blot detection sclerosteosis protein expression levels.MC3T3-E1 cells culture with MLO-Y4 cells exposed to different concentrations of titanium (Ti) particles in vitro, in order to detection of osteoblast osteogenetic activity. Results Our results showed that Ti particles inhibited cell viability of MLO-Y4 osteocytes in a dose-dependent manner. Incubation with Ti particles caused apoptosis of MLO-Y4cells.Treatment with Ti particles significantly increased expression of the osteocytic marker SOST/sclerostin. Furthermore, treatment of MLO-Y4 cells with Ti particles produced a dose-dependent decrease in ALP activity and decreased mineralization of MC3T3-E1 cells through direct cell-cell contact. Conclusions Titanium particles damage osteocytes and inhibit osteoblast differentiation.

Background: It is technically challenging to restore hip rotation center exactly in total hip arthroplasty (THA) for patients with end-stage osteoarthritis secondary to developmental dysplasia of the hip (DDH) due to the complicated acetabular morphology changes.In this study, we developed a new method to restore hip rotation center exactly and rapidly in THA with the assistance of three dimensional (3-D) printing technology.Methods: Seventeen patients (21 hips) with end-stage osteoarthritis secondary to DDH who underwent THA were included in this study. Simulated operations were performed on 3-D printed hip models for preoperative planning. The Harris fossa and acetabular notches were recognized and restored to locate acetabular center. The agreement in the size of acetabular cup and bone defect between simulated operations and actual operations were analyzed.Clinical and radiographic outcomes were recorded and evaluated.Results: The sizes of the acetabular cup of simulated operations on 3-D printing models showed a high rate of coincidence with the actual sizes in the operations(ICC value=0.930) There was no significant difference statistically between the sizes of bone defect in simulated operations and the actual sizes of bone defect in THA( t value=0.03，P value=0.97). The average Harris score of the patients was improved from (38.33±6.07) preoperatively to the last follow-up (88.61±3.44) postoperatively.The mean vertical and horizontal distances of hip rotation center on the pelvic radiographs were restored to (15.12 ± 1.25）mm and ( 32.49±2.83) mm respectively. No case presented dislocation or radiological signs of loosening until last follow-up.Conclusions: The application of 3-D printing technology faciliate orthopedists to recognize the morphology of Harris fossa and acetabular notches , locate the acetabular center and restore the hip rotation center rapidly and acurately.

Kinase-targeted therapy is a new and promising approach to disease treatment. However, some kinase inhibitors have been observed to cause an off-target adverse risk for skeletal system by influencing the growth of osteoblasts. It is known that the proliferation and differentiation of osteoblasts are essentially regulated by MAPK signaling pathway, and many off-target events are considered to influence this pathway. Here, the unexpected MAPK-inhibitor interactions in mouse MC3T3-E1 osteoblastic cells were investigated in detail using an integrative protocol. With bioinformatics analysis we successfully profiled a systematic noncognate interaction spectrum for off-target kinase inhibitors against mouse MAPK kinases, from which 13 potential MAPK-inhibitor interactions were identified. The inhibitors Nilotinib, Dasatinib and Bosutinib were suggested as promising candidates; their cytotoxicity on MC3T3-E1 and inhibitory activity against MAPK kinase were tested at cellular and molecular levels, respectively. We also tested two known MAPK inhibitors SP600125 and SB203580 as positive controls. Consequently, the Dasatinib was found to have high off-target risk for unexpectedly targeting osteoblast MAPK signaling pathway.

The tripartite motif (TRIM) protein family are implicated in a wide array of cellular processes, including cell growth, differentiation, apoptosis and inflammation. This study aimed to investigate the specific function of TRIM59 in chondrocytes and its association with the pathophysiology of osteoarthritis (OA). We observed the downregulated TRIM59 expression in OA cartilage compared to normal tissues. Overexpression of TRIM59 suppressed interleukin 1 beta (IL-1β)-induced extracellular matrix (ECM) metabolic imbalance, proinflammatory cytokine production, apoptosis and decrease in cell viability. Mechanistic analyses further revealed that IL-1β-induced activation of the NF-κB and JAK2/STAT3 pathway is suppressed upon TRIM59 overexpression. TRIM59 expression was consistently decreased in a rat OA model in vivo, and its overexpression led to inhibition of matrix metallopeptidase-13 (MMP-13) production, proinflammatory cytokine levels and increased collagen type II (collagen II) and aggrecan synthesis. Our data collectively suggest that TRIM59 plays a critical in OA development through regulation of NF-κB and JAK2/STAT3 signaling pathway. Pharmacological upregulation of TRIM59 may therefore present an effective novel therapeutic approach for OA.

Die-punch fragments refer to articular cartilage and subchondral bone embedded in cancellous bone as part of an intra-articular fracture. Bartonicek type IV posterior malleolar fractures with associated die-punch fragments are rare, and the appropriate surgical approach remains unclear. We determined outcomes, and the effect of die-punch fragment size on outcomes, for 32 patients with Bartonicek type IV posterior malleolar fractures with die-punch fragments between January 2015 and December 2017. Mean follow-up for all patients was 23.8 (range 20.0-30.0) months. At the final follow-up visit, mean ankle dorsal extension was 24.6° and plantar flexion was 40.0°; American Orthopaedic Foot and Ankle Society ankle-hindfoot score was 88.6 ± 4.3; visual analog scale weightbearing pain score was 1.5 ± 0.6; and Bargon traumatic arthritis score was 0.8 ± 0.4. There were no severe complications. We divided patients into a small-fragment (≤3 mm) group (n = 12) and large-fragment (>3 mm) group (n = 20). The Bargon scores at final follow-up were 0.5 and 1, respectively (P=.02). There were no statistically significant differences between the 2 groups for the other outcome scores at various time intervals. The posterolateral approach with distal locking plate internal fixation for Bartonicek type IV posterior malleolar fractures with die-punch fragments can result in excellent anatomical reduction of the collapsed articular surface and the displaced fragment from the tibial plafond, recovery of articular surface congruity, and maintenance of joint stability. Die-punch fragment size may not impact clinical and functional outcomes but may contribute to post-traumatic arthritis.

Simultaneous silencing of multiple upregulated genes is an attractive and viable treatment strategy for many incurable diseases including cancer. Herein we used a dual gene-targeted siRNA conjugate composed of VEGF and Survivin siRNA sequences in the same backbone to inhibit proliferation and angiogenesis in two human osteosarcoma cell lines. We synthesized siRNA sequences targeting the VEGF and Survivin genes individually (VEGF siRNA and Survivin siRNA) or simultaneously (one-chain-double-target siRNA: dual siRNA). VEGF and Survivin mRNA and protein expression levels in human osteosarcoma MG-63 and Saos-2 cells were detected by qRT-PCR and western blot analysis. VEGF and Survivin protein location and expression were evaluated by immunohistochemistry and immunofluorescence staining. MG-63 and Saos-2 cell migration, proliferation, apoptosis, and angiogenesis were detected by scratch test, MTT assay, flow cytometry, and capillary tube assay respectively. The dual siRNA induced similar downregulation of VEGF and Survivin mRNA and protein levels, compared with VEGF siRNA or Survivin siRNA alone. The dual siRNA caused greater suppression of MG-63 and Saos-2 cell migration, proliferation and angiogenesis, and promoted more cell apoptosis than VEGF siRNA or Survivin siRNA alone, suggesting that the effects of the dual siRNA on inhibiting cell proliferation, migration, and angiogenesis and promoting apoptosis were superior to those of the single-target siRNAs. Simultaneous silencing of VEGF and Survivin using the dual siRNA may be an advantageous alternative for the development of therapeutic strategies against human osteosarcoma.

Fabrication of nanotheranostic agents attracted a growing interest in accurate diagnosis and therapy of cancer by the sustainable biomineralization strategy. Herein, it is reported that biominerali...

A transient study was conducted at pilot scale to assess the impact of Fe dosage on the dynamics of biological and membrane performance of an anaerobic membrane bioreactor (AnMBR) treating authentic municipal wastewater. A transient model of the AnMBR system was employed to assist with interpretation of the observed responses in the mixed liquor under different FeCl3 dosages. A high dosage (43 mg FeCl3/LSewage) resulted in a significant accumulation of fixed suspended solids and volatile suspended solids (VSS) and reduction of colloidal COD in the mixed liquor. The elevated dosages appeared to reduce the biodegradability of VSS that was present in the raw wastewater. Intermediate dosages of FeCl3 (21–12 mg/L) had less effect on these responses and did not appear to affect VSS biodegradation. Membrane performance was significantly affected by FeCl3 dosage as indicated by reversible resistance (RR) and physically irreversible resistance (IR). RR was closely related to the colloidal COD in the mixed liquor, thus responded quickly to Fe dosage. Physically, IR had a delayed response to changes in the colloidal COD concentrations in the mixed liquor and this was attributed to the effect of slow mass transfer of colloidal matter between the mixed liquor and the membrane.

Background The aim of this article is to introduce a novel technique of limited dynamic hip screw (LDHS) in the treatment of intertrochanteric fractures and to evaluate its biomechanical effects. Material/Methods Based on the principle of providing both dynamic and static pressure to stabilize the fracture, we improved the dynamic hip screw (DHS) and designed the LDHS. Six fresh cadavers were collected and intertrochanteric fracture models were established, including Evan’s type I fracture (n=3) and type II (n=3). We used the left-to-right comparison in this study. LDHS technique was performed on the left femoral head of each cadaver (LDHS group: n=6), while DHS was performed on the right side (DHS group: n=6). After fixation by either LDHS or DHS, compressive strength, rigidity, shear stress and strain, torsional properties, and ultimate loads were measured and compared in both groups. Results Under the 1200 N pressure, compressive strength, rigidity, shear stress and strain, and ultimate loads of LDHS were better than those of DHS in the 2 groups. All differences were statistically significant. Although LDHS enhanced the torsional properties, there was no significant difference. Conclusions Our study demonstrates that the biomechanical effects of LDHS are superior than those of DHS, and there was no screw failure after implantation. Armed with those better properties, LDHS, as a new internal fixation device, may be a good alternative option in the treatment of intertrochanteric fractures.

Background To investigate the expression of long non-coding RNA (lncRNA) Snorna hostgene16 (SNHG16) in sciatic nerve injury tissues and cells. The molecular mechanism of SNHG16 regulating signal activator of transcription 3 (STAT3) expression through "sponge" adsorption of miR-93-5p was also studied. Methods A rat model of sciatic nerve injury was established, and primary Schwann cells (SCs) were extracted. The expression of SNHG16 in animal tissues with sciatic nerve injury and SCs treated with ischemia and hypoxia was detected by qPCR, and CCK-8 assay, cell scratch assay, and Transwell chamber assay were used to detect cell proliferation, migration, and invasion. The targeted binding of SNHG16 to miR-93-5p was verified by double luciferase reporter gene assay and miRNA immunoprecipitation assay. MiR-93-5p mimic, SNHG16 overexpression vector, and sh-STAT3 plasmid were transfected into cells, respectively, and the mRNA expressions of SNHG16, miR-93-5p, and STAT3 in the cells were detected by qPCR. Results The expression of lncRNA SNHG16 was decreased after sciatic nerve injury, while overexpression of SNHG16 promoted the proliferation, migration, and invasion of SCs. The results of dual luciferase reporter gene assay and miRNA immunoprecipitation reaction showed miR-93-5p interacted with SNHG16, and the overexpression of miR-93-5p reversed the promoting effects of SNHG16 on the proliferation and invasion of SCs. At the same time, the knockdown of STAT3, which is the target gene of miR-93-5p, reversed the proliferation and invasion promotion effect of SNHG16 on SCs. SNHG16 affected the expression of its downstream target gene STAT3 by adsorbing miR-93-5p via endogenous competitive sponge. Conclusions SNHG16 can regulate STAT3 expression by sponge adsorption of miR-93-5p in SCs, and SNHG16 and miR-93-5p can be used as potential targets for the diagnosis and treatment of sciatic nerve injury.

Low-dose radiation has been used in clinical and experimental models for the prevention of scarring and for fracture healing. There is evidence that low-dose radiation improves the hormesis of various cell types but little is known about its effects on peripheral nerve tissue. In this study, we investigated the beneficial effects of low-dose radiation on the regeneration of transectional peripheral nerve injury in an experimental rat model. Seventy-two male Sprague-Dawley rats received transection injury to the left sciatic nerves, and the nerves were subsequently sutured by epineurium end-to-end anastomosis to restore continuity. Animals were randomly assigned to one of two treatment groups (n = 36/group): 1 Gy X-ray irradiation or control (sham irradiation). Gait analysis, electrophysiological examination and morphological investigations were performed. In addition, Western blot and qRT-PCR were performed to determine the level of vascular endothelial growth factor (VEGF) and growth-associated protein-43 (GAP-43). Content of VEGF and GAP-43 in the regenerated sciatic nerve of the irradiated group was higher than the control group. At 4 to 12 weeks after surgery, the irradiated animals exhibited a significantly improved functional recovery relative to controls. At 12 weeks after surgery, amplitude and conduction velocity of the irradiated group were higher than the control group (P < 0.05). The number of nerve fibers, diameter of axons and morphological structure of the myelin sheath in the irradiated group were superior to those of the control group. These results suggest that low-dose radiation contributed to regeneration and functional recovery after transverse peripheral nerve injury by inducing increased production of VEGF and GAP-43, which promote the axonal regeneration and myelination.

Peripheral nerve injury is a common disease in clinic practice. Low-dose radiation exposure can increase recovery from peripheral nerve injury, but the mechanism is unclear. The objective of this study was to explore the ways that microRNAs participate in the recovery from peripheral nerve injury in rats. To explore the function of miRNAs in this process, we performed Illumina deep sequencing to investigate miRNA expression in spinal cords after X-ray irradiation. Two miRNA libraries (0 GY and 1 GY) were constructed for Illumina sequencing. The sequencing results showed that a total of 53,342,744 raw reads for the control group −0 Gy and 48,453,367 raw reads for treated group −1 Gy were obtained. After a series of selections, a total of 804 miRNAs were identified. One hundred fifty miRNAs were differentially expressed between the treated group −1 Gy and control group −0 Gy. A total of 23,652 target genes and 48,157 target sites were predicted for the 150 differentially expressed miRNAs. GO and KEGG enrichment analyses revealed that the PI3K-Akt-signaling pathway, neuroactive ligand-receptor interaction, and the MAPK signaling pathway were enriched. We demonstrated that the novelmiRNAs-360,-301,-239, and −400 targeted Vegfa and regulated its expression after irradiation. Our study revealed that many novel miRNAs were induced by X-ray irradiation, and were involved in the recovery from peripheral nerve injuries. This study provides a framework for understanding the molecular mechanisms underlying the recovery from peripheral nerve injury following exposure to X-ray irradiation.

Introduction This study aimed to investigate the effectiveness and safety of the Chinese Aircraft-shaped Sleeve (CASS) system on the clinical outcomes of tibial intermedullary nailing using a suprapatellar approach for the treatment of tibial fractures in a cohort of adult Chinese patients over a minimum one-year follow-up. Methods After institutional review board approval, skeletally mature patients with Orthopaedic Trauma Association (OTA) type 42 tibial shaft fractures were randomized into either a SP approach using CASS group or a conventional SP approach group after informed consent was obtained. The operations were performed by a single senior orthopaedic surgeon according to group assignments. A group of 33 patients were treated using the CASS system and the other group of 34 patients were treated using a conventional SP approach. Both groups fully complied with research requirements and completed 12 months of follow-up. Magnetic resonance images (MRI) were obtained for the evaluation of the patellofemoral joint (PFJ) and residual debris preoperatively, as well as one week and 12 months postoperatively. Radiographs were used to assess alignment and union, visual analog scores (VAS) were used to assess anterior knee pain, and range of motion (ROM) and the Lysholm knee scoring scales were used for evaluating the operated knee at the 12-month follow-up. Results Differences in cartilage lesion changes observed by MRI between the two groups were statistically significant (P = 0.030 at 1 week postoperatively; P = 0.025 at 12 months postoperatively). No significant differences were evident with respect to debris residue, malalignments, nonunion, VAS, ROM and Lysholm knee scoring scale with the exception of stair climbing (P = 0.02). Conclusion Based on the data of this one-year clinical follow-up study, the SP approach using the CASS system offers the potential to benefit patients suffering from tibial shaft fractures, who will be treated with intramedullary nailing especially for smaller patients.

Recently, research into the biological effects of low dose X-ray irradiation (LDI) has been a focus of interest. Numerous studies have suggested that cells exhibit different responses and biological effects to LDI compared with high doses. Preliminary studies have demonstrated that LDI may promote osteoblast proliferation and differentiation in vitro, thereby accelerating fracture healing in mice. However, the exact mechanism of action by which LDI exerts its effects remains unclear. Previous studies using microarrays revealed that LDI promoted the expression of genes associated with the cytoskeleton. In the current study, the effect of X-ray irradiation (0.5 and 5 Gy) on the morphology of MC3T3-E1 cells and fiber actin organization was investigated. Osteoblasts were treated with 0, 0.5 and 5 Gy X- ray irradiation, following which changes in the actin cytoskeleton were observed. The levels of RhoA, ROCK, cofilin and phosphorylated-cofilin were measured by reverse transcription-quantitative PCR and western blotting. Subsequently, osteoblasts were pretreated with ROCK specific inhibitor Y27632 to observe the changes of actin skeleton after X-ray irradiation. The results demonstrated that the cellular morphological changes were closely associated with radiation dose and exposure time. Furthermore, the gene expression levels of small GTPase RhoA and its effectors were increased following LDI. These results indicated that the RhoA/Rho-associated kinase pathway may serve a significant role in regulating LDI-induced osteoblast cytoskeleton reorganization.

To determine reasonable treatment of intertrochanteric fractures with proximal femoral nail anti-rotation (PFNA) or hemi-arthroplasty (HA) in elderly patients. Between January 2009 and June 2013, a total of 367 patients were admitted to the Orthopedics Department of The Second Affiliated Hospital of Soochow University. Patient data were retrospectively analyzed and included 160 males and 207 females. The ages of the patients were between 60 and 97 years and the average age was 72 +/- 3.9 years. According to the Evans-Jensen classification scheme, the fracture types were type IA (n = 18), type IB (n =3 1), type II (n=154), and type III (n = 164). A comparison between the two surgical methods (PFNA and HA) included the duration of surgery, intra-operative blood loss, post-operative weight-bearing time, implant complications, and the Harris hip score. The data were analyzed after 14-50 months (average 24 months) of follow-up. The gender and age of the patients did not differ significantly between the two methods of treatment; however, the duration of surgery between the PFNA hemi-arthroplasty groups did differ (hemi-arthroplasty required less time), the intra-operative blood loss in the PFNA group was significantly less than the hemi-arthroplasty group, and the post-operative weight-bearing time was significantly shorter in the hemi-arthroplasty group than the PFNA group. A retrospective study was conducted in 367 patients during the 42-month study period (January 2009-June 2013) to observe the efficacy of PFNA and hemi-arthroplasty. Complete data were available for analysis. There are significant advantages and disadvantages with respect to the two surgical treatment modalities. For elderly patients with unstable fractures, severe osteoporosis, and pre-operative mobility, hemi-arthroplasty is preferred because hemi-arthroplasty has fewer disadvantages compared to PFNA, which is not suitable for full weight bearing and bone union. PFNA for the treatment of intertrochanteric fractures has been increasingly accepted and widely used; however the use of arthroplasty remains controversial (3). Conservative treatment for intertrochanteric fractures in elderly patients has become a main trend and often takes longer, gives rise to more complications, and has mortality rates higher than surgical treatment.

The mechanisms driving the development and progression of Rheumatoid arthritis (RA) are complex, novel targeted therapies are gaining traction as potential methods to prevent or slow the progression of RA. Nobiletin is a derivative of citrus fruit that has been shown to attenuate the development of osteoarthritis and inhibit the expression of proinflammatory cytokines. However, the exact mechanisms by which nobiletin exerts these chondroprotective effects remain poorly understood. In the present study, we investigated the impact of nobiletin in mediating the effects of interleukin-21 (IL-21) in MH7A fibroblast-like synoviocytes (FLS), the main cell type found in the articular synovium. Firstly, we demonstrate that nobiletin (25 μM and 50 μM) reduced the expression of the IL-21 receptor by 29% and 51%, respectively, in FLS. Additionally, our findings demonstrate that nobiletin potently ameliorated IL-21-induced increased production of reactive oxygen species and 4-hydroxynonenal, increased expression of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and high-mobility group box 1 (HMGB1), and decreased mitochondrial membrane potential. We also demonstrate the ability of nobiletin to attenuate IL-21-induced expression of matrix metalloproteinases 3 and 13 (MMP-3, MMP-13), key degradative enzymes involved in RA-associated cartilage destruction. Finally, we show that the effects of nobiletin are mediated through the JAK1/STAT3 pathway, as nobiletin significantly reduced the phosphorylation of both JAK1 and STAT3. Taken together, our findings indicate that nobiletin may offer a safe and effective treatment against the development and progression of RA induced by the expression of IL-21 and its receptor.

Background Inflammation and glial scar formation determine the recovery process after spinal cord injury. Hyperbaric oxygen is used as a rehabilitation therapy for various clinical diseases, including spinal cord injury. However, the relationship between hyperbaric oxygen therapy and inflammation or glial scar is not fully understood. Objective The aim of this study was to investigate the therapeutic effect and molecular mechanism of hyperbaric oxygen on spinal cord injury. Methods A total of 54 developing female Sprague-Dawley rats were randomly divided into sham group, spinal cord injury group, and hyperbaric oxygen group, with 18 rats in each group. The model of spinal cord injury was established using Allen's method. Hyperbaric oxygen therapy was administered once a day until the rats were killed. Results The results demonstrated inflammation and glial scar formation are involved in secondary spinal cord injury. After hyperbaric oxygen treatment, there was a notable improvement of the locomotor function in rats. Hyperbaric oxygen reduced the inflammatory reaction and glial scar formation by inhibiting inflammation-related factors iNOS and COX-2 and glial scar-related components GFAP and NG2. This process may be achieved by inhibiting AKT and NF-kB pathways. Conclusions Hyperbaric oxygen effectively promotes the recovery of spinal cord injury by inhibiting inflammation and glial scar formation.

Purpose This article reports on FLVCR-AS1 effects on osteosarcoma (OS) growth. Methods Tumor tissue and adjacent normal tissue of 48 OS patients were collected. HOS and 143B cells were transfected. Gene expression was examined with qRT-PCR and Western blot. CCK8 assays and cell cloning was performed to measure cell proliferation. Cell cycle and apoptosis were assessed. Luciferase-reporter gene assays and RNA pull-down tests were used to detect targeting relationships between genes. Results Prominently higher FLVCR-AS1 expression was found in OS tissue and cells, and was associated with poor prognosis (P

BACKGROUND: The objectives of this study was to explore the activation of the extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathway and osteogenesis-related factors in the subchondral bone of patients with knee osteoarthritis (OA). METHODS: Ten patients with primary OA who underwent total knee arthroplasty in the Department of Arthritis Surgery of our hospital were enrolled, and subchondral bone tissue samples were obtained during the operation. He staining and saffron staining were used to observe the arrangement of chondrocytes in the patient tissues. The protein expression levels of JNK, p-JNK, ERK, p-ERK, Runx2 and OMD in subchondral bone were detected by Western Blot. Knee osteoarthritis mice were established. He staining was used to observe the arrangement of subchondral bone cells in the knee joint of mice. Cellular mineralized nodules were determined by alizarin red staining. RESULTS: Firstly, in general and staining, it was observed that the subchondral bone lesions of knee OA participants were obvious. Compared with normal knee joints, the levels of phosphorylation-c-Jun N-terminal kinase (P-JNK) and phosphorylation-extracellular-signal-regulated kinase (P-ERK) in the subchondral bone of knee arthritis participants were significantly increased (P

BACKGROUND This study aimed to compare the surgical outcomes between open pedicle screw fixation (OPSF) and percutaneous pedicle screw fixation (PPSF) for the treatment of thoracolumbar fractures, which has received scant research attention to date. MATERIAL AND METHODS Eight-four patients with acute and subacute thoracolumbar fractures who were treated with SSPSF from January 2013 to June 2014 at the Changzhou Hospital of Traditional Chinese Medicine (Changzhou, China) were retrospectively reviewed. The patients were divided into 4 groups: the OPSF with 4 basic screws (OPSF-4) group, the OPSF with 4 basic and 2 additional screws (OPSF-6) group, the PPSF with 4 basic screws (PPSF-4) group, and the PPSF with 4 basic and 2 additional screws (PPSF-6) group. The intraoperative, immediate postoperative, and over 1-year follow-up outcomes were evaluated and compared among these groups. RESULTS Blood loss in the PPSF-4 group and the PPSF-6 group was significantly less than in the OPSF-4 group and the OPSF-6 group (P0.05). The OPSF-6 group exhibited significantly higher immediate postoperative correction percentage of anterior column height of fractured vertebra than the other 3 groups (P0.05), and higher correction of sagittal regional Cobb angle and kyphotic angle of injured vertebra than in the PPSF-4 and -6 groups (P0.05). In addition, there was no significant difference in the correction loss of percentage of anterior column height, and loss of sagittal Cobb angle and kyphotic angle of fractured vertebrae at final follow-up among the 4 groups (P0.05). CONCLUSIONS OPSF with 6 screws had an advantage in the correction of injured vertebral height and kyphosis, and PPSF reduced the intraoperative blood loss of patients.

MicroRNA-128 (miR-128), a brain-enriched microRNA, has been reported to participate in the regulation of cell differentiation, but its potential roles in adipogenic and osteogenic differentiation of human mesenchymal stem cells (hMSCs) have not been addressed.The study was conducted to investigate the effects and mechanism of miR-128 on adipogenic and osteogenic differentiation of hMSCs.Morphology of hMSCs, lipid droplets and calcium nodules were observed and photographed by LSM microscopy. Expression of CCAAT/enhancer binding protein-α (C/EBPα), peroxisome proliferator-activated receptor-γ (PPARγ), miR-128, vascular endothelial growth factor (VEGF), osteocalcin (OCN) and Runt-related transcription factor 2 (RUNX2) was determined by RNA preparation and reverse transcription polymerase chain reaction (RT-PCR), protein expression of VEGF was analyzed by Western blot.It was suggested that miR-128 expression showed a 4.56-fold induction by adipogenic treatment and a 58.8% reduction by osteogenic treatment. Over-expression of miR-128, promoted adipogenic differentiation while inhibited osteogenic differentiation. In contrast, adipocyte formation was inhibited and osteogenesis was enhanced in cells slicing miR-128. Furthermore, over-expression of miR-128 down-regulated VEGF expression in adipogenically and osteogenically differentiated cells. We further identified VEGF as a key regulator in miR-128-induced adipogenic and osteogenic differentiation. Following knockdown of VEGF, the effects of over-expression of miR-128 on adipogenic and osteogenic differentiation of hMSCs were limited.It was indicated that miR-128 could regulate adipogenic and osteogenic differentiation of hMSCs significantly through the suppression of VEGF pathway.

Human osteoclast-stimulating factor (hOSF) is an intracellular protein produced by osteoclasts that induces osteoclast formation and bone resorption in osteoporosis by recruiting multiple signaling complexes with its diverse biological partners through peptide-mediated interactions (PMIs). The protein contains a modular peptide-recognition domain of Src homology 3 (SH3), which can recognize and bind to the polyproline regions of its partner proteins, as well as two N-terminal polyproline segments, which can be recognized and bound by the SH3 domains of its partner proteins. Here, we attempted to elucidate the complicated PMIs between the different SH3 domains and different polyprolines of hOSF and its three known interacting partners, i.e. proto-oncogene tyrosine-protein kinase (c-Src), survival motor neuron (SMN) and Src-associated in mitosis, 68 kD (Sam68). A total of 29 peptide segments containing the SH3-binding motif PXXP were extracted from these partner proteins, which are potential binding sites of hOSF SH3 domain, while the c-Src kinase also possesses a SH3 domain that may recognize and bind the two polyproline peptides at hOSF N-terminus. Structural bioinformatics analysis identified a number of biologically functional PMI candidates between these SH3 domains and these polyproline peptides, which were then tested in vitro using fluorescence spectroscopy assays. Consequently, it is found that (i) hOSF SH3 domain exhibits strong binding potency to two Sam68 peptides 36RQPPLPHR43 (K d = 13.7 μM) and 425APPARPVK432 (K d = 3.2 μM) as well as moderate affinity to three SMN peptides 193FLPPPPPM200 (K d = 56.2 μM), 235PFPSGPPI242 (K d = 28.4 μM) and 246PPPICPDS253 (K d = 74.5 μM), but has only weak or no binding to c-Src peptides. Instead, a proline-rich region at hOSF N-terminal that contains two overlapping peptides (3KPPPKPVK10 and 6PKPVKPGQ13) can be bound tightly by c-Src SH3 domain with high and moderate affinity (K d = 5.8 and 39.6 μM, respectively).

The long term impact of SRT (100-40 days) and recovery cleaning on membrane performance of an AnMBR treating authentic municipal wastewater in a large pilot plant was assessed. Successful operation of the pilot plant at a flux of 17 LMH was maintained for a period of 536 days during which the longest period of operation without recovery cleaning or membrane replacement was 178 days. Lower SRT (40 days) reduced the fouling propensity of the mixed liquor in terms of TSS concentration and the dewaterability indicators including colloidal COD (cCOD) concentration and capillary suction time (CST). Critical fluxes ranged from 21 to 23 LMH to 25-27 LMH for SRTs of 70 and 40 days respectively and this was consistent with the reduced concentrations of TSS and improved dewaterability under the latter conditions. Recovery cleaning was found to result in substantial reduction of resistance as indicated by both pilot plant operation and clean water flux tests. The long-term fouling rate was observed to be higher with cleaned membranes as compared to virgin membranes. The lower membrane fouling with virgin membranes suggested that accumulation of foulants, which were resistant to cleaning, caused the higher fouling rates for the cleaned membranes.

This study investigated the impact of Solid Retention Time (SRT) (40 to 100 days) and Hydraulic Retention Time (HRT) (2.5 to 8.5 hours) on the treatment of municipal wastewater in pilot and bench scale AnMBRs. The results revealed good permeate quality with respect to concentrations of COD (

Abnormal destruction of the components of the articular extracellular matrix (ECM) such as type II collagen and aggrecan caused by advanced glycation end products (AGEs) has been considered as one of the pathological characteristics of osteoarthritis (OA). Receptor-interacting protein 1 (RIP1), an important serine/threonine kinase, possesses a variety of biological functions including cell proliferation, survival and death. The physiological roles of RIP1 in OA have not been reported before. Here, we found that AGEs increased the expression of RIP1 in human chondrosarcoma cell line SW1353 cells. Importantly, we found that antagonism of RIP1 using its specific inhibitor necrostatin-1 (Nec-1) ameliorated AGE-induced degradation of type II collagen and aggrecan in SW1353 cells. We also found that treatment with Nec-1 reduced the expression of MMP-3 and MMP-13 but restored the expression of Tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Also, our results indicate that Nec-1 inhibited AGE-induced expression of ADAMTS-4 and ADAMTS-5. Mechanistically, we found that Nec-1 treatment inhibited the activation of JNK and the transcriptional factor AP-1 by reducing the expressions of c-Fos and c-Jun, the two main components of AP-1. Additionally, we found that Nec-1 treatment abolished AGE-induced activation of the transcriptional factor NF-κB by suppressing the nuclear translocation of p65. These findings suggest that RIP1 might be an important therapeutic target of OA.

Objective To compare the clinical efficacy of anterior cruciate ligament (ACL) reconstruction with 4-strand hamstring tendon autograft (4SHG), allograft and the Ligament Advanced Reinforcement System (LARS) ligament, and to find the causes of cumulative failure or nonreturn to sport. Design Retrospective case series. Setting Department of Orthopedic Surgery, the second affiliated hospital of Soochow University, Suzhou, Jiangsu, China. Patients Three hundred six patients with isolated ACL deficiency were included. Two hundred twenty-nine patients met the inclusion/exclusion criteria, and finally, 185 of these patients participated in this study. Interventions Anterior cruciate ligament reconstruction using 4SHG, allograft, and LARS. Main outcome measures Objective knee function, subjective knee function, and information regarding return to sport, cumulative failure, and complications. Secondary: distribution of tunnel position and tunnel enlargement. Results There were no statistically significant differences between the 3 groups regarding all the clinical objective and subjective results, return to sport, complications, or cumulative failures (P > 0.05). One hundred twenty-eight patients (69.2%, 128/185) returned to sport. Preoperative (after injury) Tegner scores were inferior to postoperative Tegner scores, and postoperative Tegner scores were inferior to preinjury Tegner scores (P Conclusions There were no statistically significant differences among the 4SHG, allograft, and LARS ligament in terms of the clinical outcomes after ACL reconstruction (ACLR) at 5-years follow-up. Interestingly, ACLR could improve the functional and motorial level of the knee, but patients had great difficulty in regaining the level of preinjury movement. In addition, the malposition of the femoral tunnel was an important cause of cumulative failure.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.