Percutaneous reduction and cannulated screw fixation assisted by 3D printing technology of calcaneal fractures in children.

BACKGROUND: Percutaneous reduction and cannulated screw fixation (PR + CSF) for treatment of calcaneal fractures in pediatric patients has been proven to achieve satisfactory outcomes with few complications. But it is also a difficult technology due to the limited exposure and surgeons are unable to reduce articular surface under direct vision. The purpose of this study was to analyze the outcomes of applying 3D printing technology to preoperative preparation and Intraoperative operating for the treatment of calcaneal fractures in children. METHODS: Pediatric patients with calcaneal fractures from January 2010 to December 2018 were reviewed during study period. Preoperative radiographs and computed tomography scans were collected to classify the fractures, reconstruct 3D printed model and evaluate postoperative outcomes. The blood loss, operative time, number of fluoroscopies, surgeon and patient satisfaction were used to assess the effectiveness, feasibility and safety of 3D printing technology. Functional results were measured by American Orthopedic Foot and Ankle Society (AOFAS) hindfoot score. RESULT: 12 patients (10 boys and 2 girls) with 17 fractures were involved in our study. There were significant differences in the average Böhler angle before operation compared with that after operation and at last follow-up (P < 0.001). Similarly, the calcaneal height and length postoperatively and at the end of follow-up time were proved to have significant difference (P < 0.05) compared to preoperative. CT scan showed good reduction of the posterior facet according to Goldzak index. The average subjective AOFAS hindfoot score was 94.1. Both patients and surgeon made sense of the 3D printed model that can help them getting more information about the factures and making preoperative plans. No wound complication was found in this study. CONCLUSION: This study indicated that percutaneous reduction and cannulated screw fixation (PR + CSF) assisted by 3D printing technology in the treatment of calcaneal fractures in pediatric patients achieve good outcomes, with specific preoperative preparation, satisfactory functional recovery and fewer complications. LEVEL OF EVIDENCE: III.

Inhibition of Histone Deacetylase 6 by Tubastatin A Attenuates the Progress of Osteoarthritis via Improving Mitochondrial Function.

Because chondrocytes are the only resident cells in articular cartilage, the steady state of these cells is important for the maintenance of joint function. In various osteoarthritis diseases, chondrocytes undergo a series of pathophysiologic changes, leading to the loss of chondrocytes and the degradation of extracellular matrix (ECM). This study found that Cytoplasmic localized histone deacetylase 6 (HDAC6) is up-regulated on the articular surface in a destabilization of the medial meniscus-induced mouse osteoarthritis model. Because HDAC6 is highly related to the acetylation of tubulin and the function of the microtubule system is closely related to material transport and signal transduction, the relationship between the expression level or activity of HDAC6 and the fate of chondrocytes in vitro and in vivo were confirmed. Primary chondrocytes overexpressing DNA-HDAC6 with plasmid were constructed in vitro, and HDAC6 inhibitor Tubastatin A was selected to inhibit HDAC6 enzyme activity in vivo and in vitro. Subsequently, mitochondrial spatial arrangement, degradation of ECM, and pathological changes in joint were defined. The results indicate that overexpression of HDAC6 causes mitochondrial dysfunction and promotes reactive oxygen species production, leading to degradation of ECM. Tubastatin A treatment after osteoarthritis ameliorates the degradation of cartilage and improves the microenvironment and function of the joint. HDAC6 may be targeted to treat osteoarthritis.

Geraniol-mediated osteoarthritis improvement by down-regulating PI3K/Akt/NF-κB and MAPK signals: In vivo and in vitro studies.

Osteoarthritis (OA) is a degenerative disease that has received increasing attention among the elderly. Its clinical manifestation is primarily long-term joint pain. Evidence for the pharmacological effects of geraniol in various diseases is accumulating. However, whether geraniol has a therapeutic effect against OA remains to be determined. In this study, we discussed the anti-inflammatory effects of geraniol in IL-1ß-induced chondrocytes and the anti-cartilage degradation effects in a mouse model of destabilization of the medial meniscus (DMM). In cell experiments, we found that the treatment of geraniol inhibited the expression of IL-1ß-induced PGE2, NO, COX-2, iNOS, TNF-α and IL-6 by western blot, qRT-PCR and immunofluorescence staining. Besides, geraniol inhibited the expression of MMP-9 and ADAMTS-5, and reversed the degradation of aggrecan and type II collagen. Mechanistically, we revealed that geraniol suppressed IL-1ß-stimulated PI3K/Akt/NF-κB and MAPK activation. Importantly, we have found in animal experiments that oral treatment of geraniol was beneficial in protecting articular cartilage from degradation. Overall, these data indicated that geraniol may have the potential to be developed as an effective treatment for OA.

Salvianolic Acid A Has Anti-Osteoarthritis Effect In Vitro and In Vivo.

Osteoarthritis (OA) is a degenerative disease found in middle-aged and elderly people, which seriously affects their quality of life. The anti-inflammatory and anti-apoptosis pharmacological effects of salvianolic acid A (SAA) have been shown in many studies. In this study, we intended to explore the anti-inflammatory and anti-apoptotic effects of SAA in OA. We evaluated the expression of pro-inflammatory mediators and cartilage matrix catabolic enzymes in chondrocytes by ELISA, Griess reaction, immunofluorescence, and Western blot, which includes nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), MMPs (MMP-3, MMP-13), and ADAMTS-5. Bax, Bcl-2, and cleaved caspase-3 were also measured by Western blot methods. The results of this experiment in vitro showed that SAA not only inhibited the production of inflammatory mediators induced by IL-1ß and the loss of cartilage matrix but also reduced the apoptosis of mouse chondrocytes induced by IL-1ß. According to the results of immunofluorescence and Western blot, SAA inhibited the activation of the NF-κB pathway and MAPK pathway. The results of these in vitro experiments revealed for the first time that SAA down-regulated the production of inflammatory mediators and inhibited the apoptosis of mouse chondrocytes and the degradation of extracellular matrix (ECM), which may be attributed to the inhibition of the activation of NF-κB and MAPK signaling pathways. In the in vivo experiments, 45 mice were randomly divided among three groups (the sham group, OA group, and OA + SAA group). The results of animal experiments showed that SAA treatment for eight consecutive weeks inhibited further deterioration of OA. These results demonstrate that SAA plays an active therapeutic role in the development of OA.

Fibroblast Growth Factor 22 Inhibits ER Stress-Induced Apoptosis and Improves Recovery of Spinal Cord Injury.

Currently, inhibiting or reducing neuronal cell death is the main strategy to improve recovery of spinal cord injury (SCI). Therapies using nerve growth factors to treat SCI mainly focused on reducing the area damaged by postinjury degeneration to promote functional recovery. In this report, we investigated the mechanism of ER (endoplasmic reticulum) stress-induced apoptosis and the protective action of fibroblast growth factor 22 (FGF22) in vivo. Our results demonstrated that ER stress-induced apoptosis plays a significant role in injury of SCI model rats. FGF22 administration promoted recovery and increased neuron survival in the spinal cord lesions of model mice. The protective effect of FGF22 is related to decreased expression of CHOP (C/EBP-homologous protein), GRP78 (glucose-regulated protein 78), caspase-12, X-box binding protein 1 (XBP1), eukaryotic initiation factor 2α (Eif-2α) and Bad which are ER stress-induced apoptosis response proteins. Moreover, FGF22 administration also increased the number of neurons and the expression of growth-associated protein 43 (GAP43) which was related to axon regeneration. We also demonstrated that the protective effect of FGF22 effectively reduces neuronal apoptosis and promotes axonal regeneration. Our study first illustrated that the function of FGF22 is related to the inhibition of ER stress-induced cell death in SCI recovery via activation of downstream signals. This study also suggested a new tendency of FGF22 therapy development in central neural system injuries, which involved chronic ER stress-induced apoptosis.

3D printing-based Ganz approach for treatment of femoral head fractures: a prospective analysis.

BACKGROUND: Femoral head fractures are uncommon injuries. Open reduction and internal fixation (ORIF) of femoral head fracture is the preferred treatment for most patients. There are several surgical approaches and treatments for this difficult fracture. However, the optimal surgical approach for the treatment of femoral head fracture remains controversial. Meanwhile, the operation is difficult and the complications are numerous. We prospectively reviewed patients with femoral head fractures managed surgically through the 3D printing-based Ganz approach to define a better approach with the least morbidity. PATIENTS AND METHODS: Between 2012 and 2017, a total of 17 patients were included in this study. An exact 1:1 3D printing model of the injured hip side was fabricated for each patient and simulated surgery was finished preoperative. The surgical approach was performed as described by Ganz. Functional assessment was performed using the modified Merle d'Aubigne scores. The reduction of the fracture was evaluated according to Matta's criteria. The incidence of complications, such as heterotopic ossification (HO) and avascular necrosis (AVN), and the need for additional surgery were also documented. RESULTS: Twelve of 17 patients (four females and eight males) were available for 2 years follow-up. The mean follow-up was 35 months (25-48 months). Average age for the 12 patients was 39.9 ± 12.2 years. According to the Pipkin classification, four patients were type I fracture, three patients were type II fracture, and five patients were type IV fracture. The mean operative time was 124.2 ± 22.1 min, and the estimated blood loss was 437.5 ± 113.1 ml. According to Merle d' Aubigne scores, excellent results were achieved in six of the 12 patients; four good and two poor results occurred in the rest of the patients. On the radiograph evaluation, fracture reduction was defined as anatomical in eight patients, and imperfect in four. Most patients had good outcomes and satisfactory hip function at last follow-up. Almost all great trochanteric osteectomy healed uneventfully. One patient developed symptomatic AVN of the femoral head and underwent THA at 3 years. After THA, she regained a good hip function with the ability to return to work and almost no reduction in sports activities. Heterotopic ossification was found in four cases (type I-1, type II-2, and type III-1). CONCLUSIONS: The 3D printing-based Ganz approach provides a safe and reliable approach and satisfactory results of treatment in femoral head fractures. Using 3D printed model for the fracture of the femoral head, the fracture can be viewed in every direction to provide an accurate description of fracture characteristics, which contributes to make a reasonable surgical plan for patients. In addition, the 3D printing-based Ganz approach can obtain excellent surgical exposure and protection of the femoral head blood supply, reduce the operation time and intraoperative blood loss, make the precise osteotomy, anatomically fix the intra-articular fragments, and effectively reduce postoperative complications. TRIAL REGISTRATION: We register our research at http://www.researchregistry.com . The Unique Identifying Number (UIN) from the Research Registry of the study is researchregistry4847 .

Urolithin A targets the PI3K/Akt/NF-κB pathways and prevents IL-1ß-induced inflammatory response in human osteoarthritis: in vitro and in vivo studies.

Osteoarthritis (OA) is a degenerative joint disease, whose progression is closely related to the inflammatory environment. Urolithin A (UA), a natural metabolite of a class of compounds (ellagitannins and ellagic acid) found in pomegranates and other fruits and nuts, has been proved to exert anti-inflammatory effects in a variety of diseases. However, the exact role of UA in OA development is still unclear. In the present study, we examined the latent mechanism of UA and its protective role in the progression of OA by both in vitro and in vivo experiments. In vitro, UA inhibited the interleukin-1 beta (IL-1ß) induced over-production of nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in a concentration-dependent manner in human OA chondrocytes. Furthermore, by downregulating the expression of metalloproteinase 13 (MMP13) and thrombospondin motifs 5 (ADAMTS5), UA attenuated the degradation of the extracellular matrix (ECM) induced by IL-1ß. Mechanistically, UA was found to suppress the activation of PI3K/Akt/NF-κB pathways. In vivo, in a surgically induced mouse OA model, UA-induced protective effects in OA development could be detected. In summary, this research suggested that UA may be adopted as a new therapeutic agent for the treatment of OA.

Sinomenine contributes to the inhibition of the inflammatory response and the improvement of osteoarthritis in mouse-cartilage cells by acting on the Nrf2/HO-1 and NF-κB signaling pathways.

Pathological changes, such as articular cartilage degeneration, destruction, and hyperosteogeny, are regarded as the main features of osteoarthritis (OA). Sinomenine (SIN) is a monomeric component purified from the plant Sinomenium acutum which has been found to have anti-inflammatory effects, however, the mechanism of action of SIN on OA is not clear. In this study, we evaluated whether SIN could regulate the inflammatory response induced by interleukin (IL)-1ß and improve outcomes in the instability model of OA (medial meniscus mice (DMM)) by acting on the Nrf2/HO-1 and NF-κ B signaling pathways in chondrocytes. From our experiments, which include Griess reaction, ELISA, Western blot, and immunofluorescence, we found that SIN not only down-regulated the expression of pro-inflammatory factors induced by IL-1ß, including; inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nitricoxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), but also decreased the production of IL-1ß-induced cartilage matrix catabolic enzymes including; ADAMTS-5 and MMPs, in mouse chondrocytes. In addition, the degradation of aggrecan and type II collagen protein in the extracellular matrix (ECM) stimulated by IL-1ß was reversed. Most importantly, we have revealed for the first time that in OA, SIN inhibited the inflammatory response and ECM degradation by activating the Nrf2/HO-1 signaling pathways and inhibiting NF-κB activity in mouse-cartilage cells. In in vivo experiments, SIN treatment helped to improve the cartilage destruction in OA model mice. In conclusion, this study has demonstrated that SIN inhibits the IL-1ß-induced inflammatory response and cartilage destruction by activating the Nrf2/HO-1 signaling pathway and inhibiting the NF-κB signaling pathway in mouse chondrocytes, suggesting a new use for SIN in the treatment of OA.

Comparison of three fixation methods in treatment of tibial fracture in adolescents.

BACKGROUND: Tibial fractures are the most common musculoskeletal injury in adolescents. The optimal management of tibial fractures in adolescents is controversial. In this study, we compared the outcomes including complications of three fixation methods in tibial fractures of adolescents and explored the factors associated with the complications. METHODS: A retrospective cohort study about 83 diaphyseal tibial fractures in 79 children and adolescents, who were treated with plate fixation (PF), elastic stable intramedullary nail fixation (ESINF), or external fixation (EF), was conducted. After adjustment for age, weight, energy of the injury, polytrauma, fracture level and pattern, and extent of comminution, treatment outcomes were compared in accordance with the length of the hospital stay, time to union, and complication rates including many factors. RESULTS: The mean age of the patients was 13.4 years, and their mean weight was 44.2 kg. There was a loss of reduction in two of 33 fractures treated with ESINF and four of 13 treated with EF (P < 0.001). At the time of final follow-up, three patients (two treated with EF and one treated with ESINF) had ≥2.0 cm of shortening. Four of the 32 patients (33 fractures) treated with ESINF underwent a reoperation (two due to loss of reduction and one each because of delayed union and nonunion). Six patients treated with EF required a reoperation (four due to loss of reduction, one for malunion and one for replacement of a pin complicated by infection). Two fracture treated with PF required refixation attributing to nonunion and malunion. A multivariate analysis with adjustment for baseline differences showed that EF was associated with a 7.56-times (95% confidence interval 3.74-29.87) greater risk of loss of reduction and/or malunion than ESINF. CONCLUSIONS: All three treatments had satisfactory outcomes, and EF was correlated with the highest rate of complications in our series of adolescents treated with a tibial fracture. However, we cannot currently recommend that all fractures might be suitable for ESINF. The choice of fixation will remain influenced by surgeon preference in term of expertise and experience, patient and fracture characteristics, and patients and family preferences.

Effect of Hypoxia on Self-Renewal Capacity and Differentiation in Human Tendon-Derived Stem Cells.

BACKGROUND Hypoxic conditions play roles in functioning of human tendon-derived stem cells (hTSCs). The goal of this study was to investigate the effect of various hypoxic conditions in self-renewal capacity and differentiation of TSCs. MATERIAL AND METHODS hTSCs was obtain from supraspinatus tendon donors. Colony formation and cell proliferation assay were used to assess the self-renewal of hTSCs. qRT-PCT and Western blot analysis were used to examine stemness and multi-differentiation potential of hTSCs. RESULTS We found that culturing at 5% O2 is more beneficial for the self-renewal of hTSCs than the other 3 culture conditions, with larger colony size and numbers. The proliferation of hTSCs in 5%, 10%, and 20% O2 cultures increased after seeding. The number of cells in the 5% O2 condition was higher than that in other culture; however, self-renewal capacity of hTSCs in 0.5% O2 was inhibited. The expression levels of stem cell markers, including NS, Nanog, Oct-4, and SSEA-4, were highest in 0.5% O2 culture. Furthermore, hTSCs cultured in 20% O2 exhibited significantly higher expression of the 3 markers (PPAR-γ, Sox-9, and Runx-2). CONCLUSIONS Hypoxic condition of culture encouraged self-renewal capacity of hTSCs, but inhibited their multi-differentiation potential, compared to normoxic condition of culture. Moreover, excessively low oxygen concentration impaired the capacity of hTSCs.

Resveratrol inhibits phosphorylation within the signal transduction and activator of transcription 3 signaling pathway by activating sirtuin 1 in SW1353 chondrosarcoma cells.

The present study assessed the mechanism by which resveratrol (Res) inhibits the growth of SW1353 chondrosarcoma cells and examined whether sirtuin 1 (Sirt1) activation affects phosphorylation within the signal transduction and activator of transcription 3 (STAT3) signaling pathway. The present study used SW1353 chondrosarcoma cells in the logarithmic phase of growth (control and treatment groups). The latter group was treated with Res at 25 and 50 µmol/l for 24 h, and cell viability, proliferation and apoptosis were analyzed using the cell counting kit­8 assay, colony counting and Hoechst staining, respectively. The expression levels of caspase­3, cleaved caspase­3, B­cell lymphoma­2 (BCL­2), BCL-2 associated X protein (Bax), STAT3 and phosphorylated (p­)STAT3) were measured by Western blotting. SW1353 cells were transfected with small interfering (si)RNA targeting Sirt1 and the expression levels of Sirt1, STAT3 and p-STAT3 were assessed. Exposure of SW1353 cells to Res reduced cell viability in a dose­dependent manner (P<0.01). Additionally, cell proliferation was significantly inhibited and the cell nuclei exhibited apoptotic characteristics. Cleaved caspase­3, Sirt1 and Bax levels were upregulated. The expression levels of BCL­2 and p­STAT3 were downregulated. Additionally, the BCL­2/Bax ratio was reduced compared with the control group. The total STAT3 level was unaffected. Res treatment activated Sirt1, however, in cells transfected with Sirt1­siRNA, the ability of resveratrol to suppress p­STAT3 expression was compromised. Overall, it was revealed that Res treatment induced apoptosis, inhibited proliferation and affected phosphorylation within the STAT3 signaling pathway by activating Sirt1 in SW1353 chondrosarcoma cells.

Hypoxia enhances tenocyte differentiation of adipose-derived mesenchymal stem cells by inducing hypoxia-inducible factor-1α in a co-culture system.

OBJECTIVES: Tissue engineering is a promising approach for repair of tendon injuries. Adipose-derived mesenchymal stem cells (ADMSCs) have gained increasing research interest for their potential in improving healing and regeneration of injured tendons. The present study aimed to investigate effects of O2 tension and potential signalling pathways on AMDSC differentiation into tenocytes, in an indirect co-culture system. MATERIALS AND METHODS: Human ADMSCs were co-cultured under normoxia (20% O2 ) and also under hypoxia (2% O2 ). Tenocyte differentiation of AMDSCs and expression of hypoxia-inducible factor-1 (HIF-1α) were analysed by reverse transcription-PCR, Western blotting and immunohistochemistry. Furthermore, HIF-1α inhibitor and inducer (FG-4592) effects on differentiation of AMDSCs were studied using qPCR, immunofluorescence and Western blotting. RESULTS: Indirect co-culture with tenocytes increased differentiation of ADMSCs into tenocytes; furthermore, hypoxia further enhanced tenocyte differentiation of AMDSCs, accompanied by increased expression of HIF-1α. HIF-1α inhibitor attenuated effects of hypoxia on differentiation of ADMSCs; in contrast, FG-4592 increased differentiation of ADMSCs under both hypoxia and normoxia. CONCLUSIONS: Taken together, we found that growing ADMSCs under hypoxia, or activating expression of HIF-1α to be important in differentiation of ADMSCs, which provides a foundation for application of ADMSCs in vivo for tendon regeneration.

[Comparison of different diameter hollow screw for the treatment of femoral neck fractures].

OBJECTIVE: To evaluate and compare the outcome of two kinds of diameter hollow screws for the treatment of femoral neck fractures. METHODS: From June 2008 to June 2013, 117 patients with femoral neck fractures were treated by closed reduction and hollow screws fixation. Among them,48 patients were fixed by 6.5 mm screw including 30 males and 18 females with an average age of (45.61 ± 11.99) years old ranging from 19 to 60 years old, involving 17 cases in Garden I/II and 31 cases in Garden III/IV; 69 patients were fixed by 8.0 mm screw including 40 males and 29 females with an average age of (45.17 ± 9.95) years old ranging from 18 to 60 years old, involving 31 cases in Garden I/II and 38 cases in Garden III/IV. The general information, operative time, hospital stay time, reduction quality, diameter of femoral head and neck, fracture healing time, the rate of fracture healing, postoperative complications were recorded and evaluated. Harris scoring was used to evaluate the hip joint function. RESULTS: All patients were followed up for 19.6 months (18 to 24 months). The difference of operative time, duration of hospitalization, quality of reduction were not statistically significant (P > 0.05). There was no difference between two groups about the average diameter of the femoral head and neck, the fracture healing time, the rate of healing and the postoperative complications (P > 0.05). There were no difference between two groups about Harris scale. There were significant difference between Garden III/IV and I /II (P > 0.05). CONCLUSION: Closed reduction and internal fixation with hollow screw in treating the young adult patients with femoral neck fracture is the first choice, both different diameters hollow screws could meet the requirements of fixation of femoral neck fracture, and not affect on fracture healing time and postoperative complications.

Silibinin alleviates high glucose-suppressed osteogenic differentiation of human bone marrow stromal cells via antioxidant effect and PI3K/Akt signaling.

High glucose is one of the possible causes for osteoporosis and fracture in diabetes mellitus. Our previous study showed that silibinin can increase osteogenic effect by stimulating osteogenic genes expression in human bone marrow stem cells (hBMSCs). However, no study has yet investigated the effect of silibinin on osteogenic differentiation of hBMSCs cultured with high glucose. The aim of this study was to evaluate the influence of high glucose on osteogenic differentiation of hBMSCs and to determine if silibinin can alleviate those effects. In this study, the hBMSCs were cultured in an osteogenic medium with physiological (normal glucose, NG, 5.5mM) or diabetic (high glucose, HG, 30mM). The effects of silibinin on HG-induced osteogenic differentiation were evaluated by alkaline phosphatas (ALP) activity assay, Von Kossa staining and real time-polymerase chain reaction. HG-induced oxidative damage was also assessed. Western blot were performed to examine the role of PI3K/Akt pathway. We demonstrated that HG suppressed osteogenic differentiation of hBMSCs, manifested by a decrease in expression of osteogenic markers and an increase of oxidative damage markers including reactive oxygen species and lipid peroxide (MDA). Remarkably, all of the observed oxidative damage and osteogenic dysfunction induced by HG were inhibited by silibinin. Furthermore, the PI3K/Akt pathway was activated by silibinin. These results demonstrate that silibinin may attenuate HG-mediated hBMSCs dysfunction through antioxidant effect and modulation of PI3K/Akt pathway, suggesting that silibinin may be a superior drug candidate for the treatment of diabetes related bone diseases.

Comparison of reconstruction plate screw fixation and percutaneous cannulated screw fixation in treatment of Tile B1 type pubic symphysis diastasis: a finite element analysis and 10-year clinical experience.

OBJECTIVE: The objective of this study is to compare the biomechanical properties and clinical outcomes of Tile B1 type pubic symphysis diastasis (PSD) treated by percutaneous cannulated screw fixation (PCSF) and reconstruction plate screw fixation (RPSF). MATERIALS AND METHODS: Finite element analysis (FEA) was used to compare the biomechanical properties between PCSF and RPSF. CT scan data of one PSD patient were used for three-dimensional reconstructions. After a validated pelvic finite element model was established, both PCSF and RPSF were simulated, and a vertical downward load of 600 N was loaded. The distance of pubic symphysis and stress were tested. Then, 51 Tile type B1 PSD patients (24 in the PCSF group; 27 in the RPSF group) were reviewed. Intra-operative blood loss, operative time, and the length of the skin scar were recorded. The distance of pubic symphysis was measured, and complications of infection, implant failure, and revision surgery were recorded. The Majeed scoring system was also evaluated. RESULTS: The maximum displacement of the pubic symphysis was 0.408 and 0.643 mm in the RPSF and PCSF models, respectively. The maximum stress of the plate in RPSF was 1846 MPa and that of the cannulated screw in PCSF was 30.92 MPa. All 51 patients received follow-up at least 18 months post-surgery (range 18-54 months). Intra-operative blood loss, operative time, and the length of the skin scar in the PCSF group were significantly different than those in the RPSF group. No significant differences were found in wound infection, implant failure, rate of revision surgery, distance of pubic symphysis, and Majeed score. CONCLUSION: PCSF can provide comparable biomechanical properties to RPSF in the treatment of Tile B1 type PSD. Meanwhile, PCSF and RPSF have similar clinical and radiographic outcomes. Furthermore, PCSF also has the advantages of being minimally invasive, has less blood loss, and has shorter operative time and skin scar.

Anatomical measurement and finite element study on screw channel parameter in percutaneous fixation of canulated screw for symphyseolysis.

To provide anatomical basement for symphyseolysis treatment with percutaneous fixation of canulated screw, through anatomical measurement on pubic symphysis and the surrounding tissues, and conduct the finite element studies on screw channel parameters. 20 cases of normal pelvic specimens from embalmed adult cadavers were taken to measure the anatomical parameter of bony remark of pubic symphysis and the space between spermatic cord (round ligament of the uterus) and pubic tubercle. Anatomical measurement results showed that the narrowest diameter of the superior ramus of pubis was 9.127 ± 1.189 mm, distance between two pubic tubercles was 55.656 ± 3.780 mm, thickness of the upper pubic symphysis was 10.510 ± 0.814 mm, and distance between upper and lower pubic symphysis was 40.872 ± 1.211 mm; the distance between round ligament of the uterus and pubic tubercle was 4.408 ± 0.304 mm, and the distance between spermatic cord and pubic tubercle was 5.196 ± 0.251 mm. The angle between canulated screw guide pin and horizontal plane was 8.342 ± 2.152°, the one between guide pin and coronal plane was 5.236 ± 1.612°, and the distance from entry point to the outer edge of pubic tubercle was 10.023 ± 1.245 mm, which was measured by Mimics software. Percutaneous surgery at horizontal position was simulated on cadaver. And the screw was correctly placed in postoperative imaging examination. According to the anatomical data and finite element studies of screw channel parameter in percutaneous fixation of canulated screw for symphyseolysis, the method can improve the accuracy of screw placement and reduce complications.

SeMet mediates anti-inflammation in LPS-induced U937 cells targeting NF-κB signaling pathway.

In previous studies, selenium (Se) was reported to play critical roles in anti-inflammatory activities. Nevertheless, limited information could be obtained during inflammation about selenomethionine (SeMet) in U937 human macrophage cells. The purpose of this study was to investigate the effects of SeMet on the inflammatory responses to lipopolysaccharide (LPS)-induced U937 macrophage cells and the signaling pathways targeted. U937 cells were pretreated with SeMet (1 µM) and subsequently induced with LPS (1 µg/ml) for 24 h. In the cell counting kit-8 assay (CCK-8), SeMet significantly inhibits the proliferation of U937 cells. SeMet also inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) stimulated by LPS. In the Western blot assay and real-time polymerase chain reaction (RT-PCR), SeMet significantly reduced protein expression and production of inducible NO synthase (iNOS), tumor necrosis factor-alpha (TNF-α), and COX-2 in U937 cells. Furthermore, SeMet markedly suppressed the LPS-mediated activation of nuclear factor-kappa B (NF-κB) by blocking the degradation of inhibitor-κB proteins (IκBα) and lessening the translocations of P50 subunit content of NF-κB in the nucleus. These findings suggested the anti-inflammatory activity of SeMet in U937 cells; indicating that SeMet might be a potential treatment for inflammation therapy.

Myricetin enhances osteogenic differentiation through the activation of canonical Wnt/ß-catenin signaling in human bone marrow stromal cells.

Myricetina flavonoid compound, has been reported to possess antioxidative, antiproliferative and anti-inflammatory effects. However, no study has yet investigated the effect of myricetin on osteogenic differentiation of human bone marrow stem cells (hBMSCs). This study was designed to investigate the effects of myricetin on osteogenic differentiation of hBMSCs in vitro. Cell viability was analyzed by MTT and osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity assay, Alizarin red S dye, real time-polymerase chain reaction (RT-PCR) and Western blot analysis. We found that the ALP activity and the mineralization of hBMSCs were enhanced by treatment with myricetin. Myricetin increased the mRNA expressions of Osteocalcin (OCN), Collagen type I (COL-I), ALP and Runt-related transcription factor 2 (RUNX2). Additionally, we found that myricetin activated the Wnt/ß-catenin pathway and increased the expression of several downstream genes including T-cell factor-1(TCF-1) and lymphoid enhancer factor-1 (LEF-1). Depletion of ß-catenin almost completely blocked the positive role of myricetin on osteogenic differentiation. Taken together, our findings suggest that myricetin enhanced osteogenic differentiation of hBMSCs by activating the Wnt/ß-catenin signaling. The study may aid in the development of a therapeutic approach utilizing myricetin for the enhancement of bone health and prevention of osteoporosis.

[Comparison of three fixation methods for the treatment of tibial fractures in adolescents].

OBJECTIVE: To explore the fixation methods in treatment of tibial fracture in adolescents by comparing the results and complications of three fixation methods and to determine the factors related to those complications. METHODS: From January 2007 to January 2012, 83 diaphyseal tibial fractures in 79 adolescents were treated with elastic stable intramedullary nail fixation, plate fixation, or external fixation respectively. There were 55 males and 24 females with an average age of 13.9 years (ranging from 11 to 17.6 years). Outcomes were compared in terms of the hospital stay,time to union, complications, and reoperation rates. RESULTS: All patients were followed up for 15.8 months in average. The time to union was significant associated with the pattern of fixation, energy of the injury, multiple and open fracture. The time of bone union of external fixation group was longer than that of elastic stable intramedullary nail fixation and plate fixation groups. But complication rates of external fixation group were higher than that of elastic stable intramedullary nail fixation and plate fixation groups. Four patients were treated with elastic nail fixation underwent a reoperation (loss of reduction in 2 cases, delayed union and nonunion in each 1 case). Six patients were treated with external fixation required a reoperation (loss of reduction in 3 cases, malunion in 2 cases, and replacement of a pin canal infection in 1 case). Two fractures were treated with plate fixation required refixation following nonunion and malunion. A multivariate analysis with adjustment for baseline differences showed external fixation to be associated with a 7.56 times (95% confidence interval=3.74 to 29.87) greater risk of loss of reduction and (or) malunion than elastic stable intramedullary nail fixation. At the final follow-up,there were agreeable results among three groups and no significant differences among them in final therapeutic effect (P>0.05). CONCLUSION: External fixation for treatment of tibial fracture in adolescents has the highest rate of complications than the other two fixation methods. Elastic stable intramedullary nail fixation can achieve the same effect of other fixed system and avoid most of the complications. Operation method choice depends on the experience of doctors and patients' basic situation and the fracture types.

Cordycepin prevented IL-ß-induced expression of inflammatory mediators in human osteoarthritis chondrocytes.

PURPOSE: Cordycepin, a nucleoside derivative isolated from Cordyceps, has been reported to exert anti-inflammatory, antitumor, antidiabetic and renoprotective effects. Osteoarthritis (OA) is a degenerative joint disease with an inflammatory component that drives the degradation of cartilage extracellular matrix. This study aimed to assess the effects of cordycepin on human OA chondrocytes. METHODS: In this study, human OA chondrocytes were pretreated with cordycepin at 10, 50 or 100 µM and subsequently stimulated with interleukin-1ß (IL-1ß) (5 ng/ml) for 24 h. Production of prostaglandin E2 (PGE2) and nitric oxide (NO) were evaluated by the Griess reaction and an enzyme-linked immunosorbent assay (ELISA). Gene expression of matrix metalloproteinase (MMP)-13, IL-6, inducible nitric oxide synthase (iNOS) and cyclo-oxygenase (COX-2) was measured by real-time polymerase chain reaction (PCR). MMP-13 and IL-6 proteins in culture medium were determined using cytokine-specific ELISA. Western immunoblotting was used to analyse the iNOS and COX-2 protein production in culture medium. Nuclear factor kappa-B (NF-κB) activity regulation was explored using Western immunoblotting. RESULTS: Pretreatment with cordycepin significantly inhibited the production of PGE2 and NO induced by IL-1ß. Cordycepin also significantly decreased the IL-1ß-stimulated gene expression and production of MMP-13, IL-6, iNOS and COX-2 in OA chondrocytes. Pretreatment with cordycepin attenuated IL-1ß-induced activation of NF-κB by suppressing degradation of its inhibitory protein nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α) in the cytoplasm. CONCLUSIONS: We show for the first time the anti-inflammatory activity of cordycepin in human OA chondrocytes. Thus, with this unique profile of actions, cordycepin may prove to be a potentially attractive and new therapeutic/preventive agent for OA.