Nurses' Working Experiences of Their Provision of Cross-Cultural Services to Tibetan Patients With Kashin-Beck Disease: A Qualitative Study.

INTRODUCTION: Limited qualitative studies exist on nurses' experience in terms of communicating with and caring for patients with endemic diseases. The purpose of this study was to describe the working experiences of nurses caring for Tibetan patients with Kashin-Beck disease in China. METHOD: A qualitative design was used in this study. Sixteen nurses who worked in the orthopedics department of a large tertiary general hospital in Wuhan, China, constituting a purposive sample, were interviewed face-to-face using semi-structured guided questions. RESULTS: Three major themes and nine subthemes were identified. Major themes included the challenge in cross-cultural nursing, stress adjustment in cross-cultural nursing, and reshaping competencies in cross-cultural nursing. DISCUSSION: This study revealed that nurses encountered multifaceted challenges when caring for Tibetan patients with Kashin-Beck disease. In a multiethnic society, communication and language skills, cultural competency and cultural sensitivity, and diverse training methods to improve cross-cultural knowledge could increase ethnic minority patient satisfaction with cross-cultural care.

Reprogrammed mesenchymal stem cells derived from iPSCs promote bone repair in steroid-associated osteonecrosis of the femoral head.

BACKGROUND: Cellular therapy based on mesenchymal stem cells (MSCs) is a promising novel therapeutic strategy for the osteonecrosis of the femoral head (ONFH), which is gradually becoming popular, particularly for early-stage ONFH. Nonetheless, the MSC-based therapy is challenging due to certain limitations, such as limited self-renewal capability of cells, availability of donor MSCs, and the costs involved in donor screening. As an alternative approach, MSCs derived from induced pluripotent stem cells (iPSCs), which may lead to further standardized-cell preparations. METHODS: In the present study, the bone marrow samples of patients with ONFH (n = 16) and patients with the fracture of the femoral neck (n = 12) were obtained during operation. The bone marrow-derived MSCs (BMSCs) were isolated by density gradient centrifugation. BMSCs of ONFH patients (ONFH-BMSCs) were reprogrammed to iPSCs, following which the iPSCs were differentiated into MSCs (iPSC-MSCs). Forty adult male rats were randomly divided into following groups (n = 10 per group): (a) normal control group, (b) methylprednisolone (MPS) group, (c) MPS + BMSCs treated group, and (d) MPS + iPSC-MSC-treated group. Eight weeks after the establishment of the ONFH model, rats in BMSC-treated group and iPSC-MSC-treated group were implanted with BMSCs and iPSC-MSCs through intrabone marrow injection. Bone repair of the femoral head necrosis area was analyzed after MSC transplantation. RESULTS: The morphology, immunophenotype, in vitro differentiation potential, and DNA methylation patterns of iPSC-MSCs were similar to those of normal BMSCs, while the proliferation of iPSC-MSCs was higher and no tumorigenic ability was exhibited. Furthermore, comparing the effectiveness of iPSC-MSCs and the normal BMSCs in an ONFH rat model revealed that the iPSC-MSCs was equivalent to normal BMSCs in preventing bone loss and promoting bone repair in the necrosis region of the femoral head. CONCLUSION: Reprogramming can reverse the abnormal proliferation, differentiation, and DNA methylation patterns of ONFH-BMSCs. Transplantation of iPSC-MSCs could effectively promote bone repair and angiogenesis in the necrosis area of the femoral head.

Icariin promotes wound healing by enhancing the migration and proliferation of keratinocytes via the AKT and ERK signaling pathway.

Icariin is a traditional Chinese drug that has long been used to treat various diseases. In the present study, the effect of icariin was investigated on cutaneous wound healing. Using in vitro experiments, it was demonstrated that icariin significantly promoted the migration and proliferation of keratinocytes via the activation of AKT serine/threonine kinase 1 (AKT) and extracellular signal­regulated kinase (ERK). Inhibition of AKT or ERK reversed the effects of icariin on the proliferation and migration of keratinocytes. In addition, icariin inhibited the production of interleukin (IL)­6 and tumor necrosis factor (TNF)­α and induced the production of IL­10. Finally, animal experiments demonstrated that icariin treatment accelerated the wound closure rate. The present findings revealed that icariin may be a promising drug to promote the migration and proliferation of keratinocytes, and to accelerate the healing of skin wounds, through its role in the upregulation of AKT and ERK signaling.

Primary total knee arthroplasty using constrained condylar knee design for severe deformity and stiffness of knee secondary to post-traumatic arthritis.

BACKGROUND: Key to a successful outcome of total knee arthroplasty (TKA) is to attain optimum alignment, adequate balance, and deformity correction. In primary TKA, this can be achieved efficiently by posterior stabilized (PS) design with or without the sub-periosteal release. However, certain circumstances such as post-traumatic arthritis are often associated with severe deformities with a significant bone defect, stiffness, and instability. Such deformities are extremely difficult to balance with soft tissue release only and require additionally constrained prostheses even in primary TKA. In such situation, constrained condylar knee (CCK) design is the ultimate choice. This study primarily aimed to report on clinical outcome, regain of function, and complication of patients who underwent primary CCK-TKA for severe deformity of the knee secondary to post-traumatic arthritis. The secondary aim was to find out the mid-term prostheses survival. METHODS: Between February 2007 and November 2013, 38 consecutive patients with post-traumatic arthritis of the knee received cemented primary CCK-TKA. Thirty-four patients (21 men and 13 women) who had a minimum of 3 years follow-up were included in this retrospective study. We used Knee Society Score (KSS), Hospital for Special Surgery (HSS) score, and roentgenographic evaluation form to assess the patients. Prostheses survival was assessed using Kaplan-Meier's survival analysis. RESULTS: Patients were followed up for an average duration of 6.47 years. KSS knee score improved from 44 points (23-68) pre-operatively to 91 points (76-100) post-operatively [P < 0.001]. The average KSS functional score improved from 49 points (20-75) pre-operatively to 91 points (65-100) post-operatively [P < 0.001]. The average HSS score improved from 51 points (27-83) pre-operatively to 91 points (75-100) post-operatively [P < 0.001]. Similarly, the average ROM improved from 68.09° ± 35.99° (0°-120°) to 113.68° ± 8.90° (100°-130°) post-operatively [P < 0.001]. The average hip-knee-ankle (HKA) angle was 176.88° ± 14.48° (135°-199°) pre-operatively and 180.24° ± 1.77° (175°-184°) post-operatively. Radiolucencies were evident in 13 knees, mostly on the tibial side. Prostheses survival was 94.7% at a mean follow-up of 6.47 years. CONCLUSION: Despite severe deformity, instability, and stiffness at a relatively young age, mid-term follow-up of primary CCK-TKA in post-traumatic arthritis provides satisfactory clinical and functional outcomes with 94.7% prostheses survival. However, it is not without complication.

Treatment of chronic ulcer in diabetic rats with self assembling nanofiber gel encapsulated-polydeoxyribonucleotide.

OBJECTIVE: This study aims to explore the treatment effects of chronic ulcer in diabetic rats with self assembling nanofiber gel encapsulated-polydeoxyribonucleotide. METHODS: Diabetic skin ulcer mouse model was established in this study. They were divided into control group, common wound group and infectious wound group. Human embryonic fibroblast cells and vascular endothelial cells were treated with short poly-N-acetyl glucosamine nanofibers and polydeoxyribonucleotide. Their effects on cell proliferation, revascularization and inhibiting infection were detected by RT-PCR, western-blotting, HE staining and immunohistochemical methods respectively. RESULTS: The expression levels of cytokines and angiogenic factors increased in the treatment groups especially in sNAG encapsulated-PDRN group. HE staining results indicated that PDRN, sNAG and sNAG encapsulated-PDRN could improve the wound healing, immunohistochemical results showed that PDRN, sNAG and sNAG encapsulated-PDRN promoted cell proliferation and new vessel formation especially sNAG encapsulated-PDRN. CONCLUSIONS: sNAG encapsulated-PDRN may have a potential application in the treatment of diabetic ulcers and chronic wound healing.

Mid-term outcomes of primary constrained condylar knee arthroplasty for severe knee deformity.

This study aimed to examine the clinical and radiographic outcomes of primary total knee arthroplasy (TKA) with use of NexGen® Legacy® Constrained Condylar Knee (CCK) prosthesis for severe knee deformity. Clinical data of 46 patients (48 knees in total, aged 61 years on average) with severe knee deformity who underwent TKA with NexGen® Legacy® CCK prosthesis between December 2007 and February 2012 were retrospectively analyzed. There were 34 knees with severe valgus with incompetent medial collateral ligament, 11 knees with severe flexion contracture with inability to achieve knee balancing in flexion and extension by posterior soft tissue release, 2 knees with Charcot arthritis with severe varus and bone loss, and 1 with traumatic osteoarthritis with severe varus and ligamentous instability. The mean duration of follow-up was 71 months (range 40-90 months). The New Knee Society scoring (NKSS) system and the Hospital for Special Surgery (HSS) score were used to evaluate the functional and clinical outcomes. Visual Analogue Scale (VAS) was used for pain measurement and Knee Society criteria for evaluation of radiological images. The results showed that, in the total 48 knees, 1 case of loosening due to short-stem tibial component at 3 months post-operatively underwent revision. The 6-year prosthesis survival rate in this cohort was 97.9%. There was no component infection occurring within 6 years. Significant post-operative improvements were found in NKSS and HSS scores. Patient satisfaction was significantly increased. Pain score was decreased significantly. Total functional score was improved from 31.46±11.43 to 86.42±8.87, range of motion (ROM) from 42.42°±23.57° to 95.31°±23.45° and the flexion contracture from 5.31°±7.87° to 0.92°±1.80°. Preoperative radiographic study showed excessive valgus (≥7°) in 37 knees, and varus deformity in 3 knees. Post-operative femorotibial alignment was valgus 3.88°±1.76° in 48 knees. Antero/posterior (A/P) view of X-ray films showed 4 radiolucent lines (RLL) in 48 tibial components. It was concluded that TKA with CCK is effective for the treatment of the severe unstable knee that cannot be balanced by soft tissue.

Preparation of a novel composite nanofiber gel-encapsulated human placental extract through layer-by-layer self-assembly.

Aqueous human placenta extract (HPE) has been previously used to treat chronic soft tissue ulcer; however, the optimal dosage of HPE has yet to be elucidated. The present study investigated a novel nanofiber gel composed through layer-by-layer (LbL) self-assembly, in which HPE was encapsulated. IKVAV, RGD, RAD16 and FGL-PA were screened and combined to produce an optimal vehicle nanofiber gel through LbL assembly. Subsequently, the aqueous HPE was encapsulated into this nanofiber at the appropriate concentration, and the morphology, particle size, drug loading efficacy, encapsulation rate, release efficiency and structure validation were detected. The encapsulation efficiency of all three HPE samples was >90%, the nanofiber gel exhibited a slow releasing profile, and the structure of HPE encapsulated in the nanofiber gel was unvaried. In conclusion, this type of novel composite nanocapsules may offer a promising delivery system for HPE.

MiR-708 promotes steroid-induced osteonecrosis of femoral head, suppresses osteogenic differentiation by targeting SMAD3.

Steroid-induced osteonecrosis of femoral head (ONFH) is a serious complication of glucocorticoid (GC) use. We investigated the differential expression of miRs in the mesenchymal stem cells (MSCs) of patients with ONFH, and aimed to explain the relationship between GC use and the development of MSC dysfunction in ONFH. Cells were collected from bone marrow of patients with ONFH. Samples were assigned to either GCs Group or Control Group at 1:1 matched with control. We then used miRNA microarray analysis and real-time PCR to identify the differentially expressed miRs. We also induced normal MSCs with GCs to verify the differential expression above. Subsequently, we selected some of the miRs for further studies, including miRNA target and pathway prediction, and functional analysis. We discovered that miR-708 was upregulated in ONFH patients and GC-treated MSCs. SMAD3 was identified as a direct target gene of miR-708, and functional analysis demonstrated that miR-708 could markedly suppress osteogenic differentiation and adipogenesis differentiation of MSCs. Inhibition of miR-708 rescued the suppressive effect of GC on osteonecrosis. Therefore, we determined that GC use resulted in overexpression of miR-708 in MSCs, and thus, targeting miR-708 may serve as a novel therapeutic biomarker for the prevention and treatment of ONFH.

Outcomes observed during a 1-year clinical and radiographic follow-up of patients treated for 1- or 2-level cervical degenerative disease using a biodegradable anterior cervical plate.

OBJECTIVE The purpose of this study was to present an initial surgical experience in the management of 1- or 2-level degenerative disc disease of the cervical spine using biodegradable anterior cervical plates (bACPs) in anterior cervical discectomy and fusion (ACDF). The authors also aimed to provide insight into this critical and controversial clinical issue by clarifying outcomes for patients receiving bACPs and by comparing their outcomes with those achieved using a traditional metallic anterior cervical plate (mACP) implant. METHODS A retrospective review was conducted for 2 series of patients who had undergone ACDF using either bACP (31 patients, 38 segments) or mACP (47 patients, 57 segments) instrumentation. The patients were followed up for a mean 13.5 ± 0.9 months (range 12-18 months) in the bACP group and 14.8 ± 1.5 months (range 14-22 months) in the mACP group. Clinical outcomes were determined according to scores on the visual analog scale (VAS), the modified Japanese Orthopaedic Association (mJOA) scoring system, and Odom's criteria. Radiological images were used to assess fusion rates, intervertebral height, Cobb's angle, and the width of prevertebral soft tissue. RESULTS Both VAS and mJOA scores were significantly improved at each follow-up in both groups. Excellent or good results according to Odom's criteria were achieved in 93.5% (29/31) of patients in the bACP group and 93.6% (44/47) of patients in the mACP group. At 6 months postoperatively, the fusion rate was 94.7% (36/38) in the bACP group and 96.5% (55/57) in the mACP group, but subsidence of the intervertebral space at the surgical level was more evident in the bACP group. Angulation, as measured by Cobb's angle, demonstrated obvious healing in both groups, while better maintenance was observed in the mACP group. The local inflammatory reaction was uneventful during follow-up. Dysphonia and dysphagia were observed in both groups during the follow-up. CONCLUSIONS The relatively comparable early clinical and radiographic outcomes and the overall acceptable complication rates for bACP and mACP use suggest that bACPs could be used as alternative instruments in ACDF. Mild graft resorption was noted without evidence of symptoms. However, the prospective efficacy of biodegradable instrumentation can only be elucidated with longer-term observation.

Low-intensity treadmill exercise promotes rat dorsal wound healing.

In order to investigate the promoting effect of low-intensity treadmill exercise on rat dorsal wound healing and the mechanism, 20 Sprague-Dawley rats were randomly divided into two groups: exercise group (Ex) and non-exercise group (non-ex). The rats in Ex group were given treadmill exercise for one month, and those in non-ex group raised on the same conditions without treadmill exercise. Both groups received dorsal wound operation with free access to food and water. By two-week continuous observation and recording of the wound area, the healing rate was analyzed. The blood sample was collected at day 14 post-operation via cardiac puncture for determination of the number of endothelial progenitor cells (EPCs) by flow cytometry, and the concentrations of relevant cytokines such as basic fibroblast growth factor (bFGF), endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) were measured by ELISA. The skin tissue around the wound was dissected to observe the vascular density under the microscope after HE staining, to detect the mRNA level of VEGFR2 and angiopoietin-1 (Ang-1) receptor using RT-qPCR, and protein expression of a-smooth muscle actin (αSMA) and type III collagen (ColIII) using Western blotting. It was found that the wound area in Ex group was smaller at the same time point than in non-ex group. The number of circulating EPCs was greater and the concentrations of vasoactive factors such as VEGF, eNOS and bFGF were higher in Ex group than in non-ex group. HE staining displayed a higher vessel density in Ex group than in non-ex group. Moreover, the mRNA expression of VEGFR2 and Ang-1 detected in the wound tissue in Ex group was higher than in non-ex group. Meanwhile, the protein expression of αSMA and ColIII was more abundant in Ex group than in non-ex group. Conclusively, the above results demonstrate Ex rats had a higher wound healing rate, suggesting low-intensity treadmill exercise accelerates wound healing. The present work may provide some hint for future study of treating refractory wound.

NVP-TAE684 reverses multidrug resistance (MDR) in human osteosarcoma by inhibiting P-glycoprotein (PGP1) function.

BACKGROUND AND PURPOSE: Increased expression of P-glycoprotein (PGP1) is one of the major causes of multidrug resistance (MDR) in cancer, including in osteosarcoma, which eventually leads to the failure of cancer chemotherapy. Thus, there is an urgent need to develop effective therapeutic strategies to override the expression and function of PGP1 to counter MDR in cancer patients. EXPERIMENTAL APPROACH: In an effort to search for new chemical entities targeting PGP1-associated MDR in osteosarcoma, we screened a 500+ compound library of known kinase inhibitors with established kinase selectivity profiles. We aimed to discover potential drug synergistic effects among kinase inhibitors and general chemotherapeutics by combining inhibitors with chemotherapy drugs such as doxorubicin and paclitaxel. The human osteosarcoma MDR cell lines U2OSR2 and KHOSR2 were used for the initial screen and secondary mechanistic studies. KEY RESULTS: After screening 500+ kinase inhibitors, we identified NVP-TAE684 as the most effective MDR reversing agent. NVP-TAE684 significantly reversed chemoresistance when used in combination with doxorubicin, paclitaxel, docetaxel, vincristine, ET-743 or mitoxantrone. NVP-TAE684 itself is not a PGP1 substrate competitive inhibitor, but it can increase the intracellular accumulation of PGP1 substrates in PGP1-overexpressing cell lines. NVP-TAE684 was found to inhibit the function of PGP1 by stimulating PGP1 ATPase activity, a phenomenon reported for other PGP1 inhibitors. CONCLUSIONS AND IMPLICATIONS: The application of NVP-TAE684 to restore sensitivity of osteosarcoma MDR cells to the cytotoxic effects of chemotherapeutics will be useful for further study of PGP1-mediated MDR in human cancer and may ultimately benefit cancer patients.

p53 overexpression increases chemosensitivity in multidrug-resistant osteosarcoma cell lines.

PURPOSE: Multidrug resistance (MDR) is a major obstacle to the successful treatment of osteosarcoma with chemotherapy. Effectiveness of cancer therapy correlates with the ability to induce a p53-dependent apoptotic response. p53 is a tumor suppressor gene that is mutated in 22 % of osteosarcomas. While impaired p53 has been implicated in the oncogenesis of osteosarcoma, it is unclear whether overexpression of wild-type p53 can increase chemosensitivity in MDR osteosarcoma cells. METHODS: We transfected a plasmid encoding the wild-type p53 gene to MDR osteosarcoma cell lines, which have different p53 statuses, U-2OSR2 with wild-type p53 (Wt-p53) and KHOSR2 with mutant p53 (Mt-p53), and determined the effect of p53 overexpression on chemosensitivities. RESULTS: Both of the U-2OSR2 and KHOSR2 cell lines displayed similar trends in p53-induced drug sensitivities. However, it seems that the impact of p53 overexpression is different based on the differential intrinsic p53 status in these cell lines. In the KHOSR2 cell line (Mt-p53), overexpression of p53 up-regulates the expression of pro-apoptotic protein p21 and Bax, while in the U-2OSR2 cell line (Wt-p53), overexpression of p53 down-regulates IGF-1r expression significantly. CONCLUSIONS: These results demonstrated that transfection of wild-type p53 increases chemosensitivity either through inhibiting IGF-1r or through increasing the expression of pro-apoptotic proteins p21 and Bax in human MDR osteosarcoma cell lines.

Elevated expression of microRNA-30b in osteoarthritis and its role in ERG regulation of chondrocyte.

ERG (ETS-related gene) belongs to the ETS family of transcription factors, and has been recently reported to contribute to homeostatic balance in skeleton cell plasticity. MicroRNA-30 (miR-30) family is also demonstrated to play a role in controlling chondrocyte differentiation. The current study investigated the miR-30b and ERG expression in articular cartilage of osteoarthritis (OA) patients. A total of 20 subjects, with 10 OA patients and 10 healthy participants, were included in this study. Human chondrosarcoma cell line SW1353 was used to explore the relationship of miR-30b and ERG in vitro. In OA patients, a significant increase of miR-30b and a decrease of ERG were observed in articular cartilage compared with Normal ones. MiR-30b mimic down-regulated the ERG mRNA and protein expression levels, while miR-30b inhibitor up-regulated ERG expression. In addition, miR-30b mimic also decreased the mRNA expression of COL2a and aggrecan, while miR-30b inhibitor had the opposite effect. Luciferase reporter assay confirmed that miR-30b targeted ERG. In conclusion, miR-30b was involved in the process of OA, and it probably functioned through its target gene ERG.

MicroRNA-16-5p Controls Development of Osteoarthritis by Targeting SMAD3 in Chondrocytes.

MicroRNAs (miRNA), small noncoding RNA molecules, are endogenous regulators of gene expression that have been implicated in the pathogenesis of various diseases such as cancer and arthritis. The aim of this study was to explore the biological function of microRNA-16-5p (miR-16-5p) and the molecular mechanism in osteoarthritis (OA). MiRNA targets were identified using bioinformatics. Using real-time PCR, the expression of miR-16-5p and SMAD3 in cartilage specimens was determined in 10 patients with knee OA and in 10 traumatic amputees (control). Functional analysis of miR-16-5p in chondrocytes was performed at both mRNA and protein levels after miRNA transfection. A luciferase reporter assay was used to verify interaction between miRNA and target mRNA. Expression of miR-16-5p was significantly higher in OA cartilages than in healthy cartilages. The data from the reporter assay and western blots indicated that miR-16- 5p regulated SMAD3 expression. Functional analysis showed that miR-16-5p could reduce expression of type IIcollagen and aggrecan while inducing expression of matrix metalloproteinases and ADAMTS; however, miR-16-5p inhibition could reverse these effects. Our results indicate that miR-16-5p is an important regulator of SMAD3 expression in human chondrocytes and may contribute to the development of OA.

Restrictive Fluid Resuscitation Leads to Better Oxygenation than Non-Restrictive Fluid Resuscitation in Piglets with Pulmonary or Extrapulmonary Acute Respiratory Distress Syndrome.

BACKGROUND: Early goal-directed therapy (EGDT) is used to reduce mortality from septic shock and could be used in early fluid resuscitation of acute respiratory distress syndrome (ARDS). The aim of the present study was to assess the effects of restrictive (RFR) and nonrestrictive fluid resuscitation (NRFR) on hemodynamics, oxygenation, pulmonary function, tissue perfusion, and inflammation in piglets with pulmonary or extrapulmonary ARDS (ARDSp and ARDSexp). MATERIAL AND METHODS: Chinese miniature piglets (6-8 weeks; 15 ± 1 kg) were randomly divided into 2 groups (n=12/group) for establishing ARDSp and ARDSexp models, and were further divided into 2 subgroups (n=6/subgroup) for performing RFR and NRFR. Piglets were anesthetized and hemodynamic, pulmonary, and oxygenation indicators were collected at different time points for 6 hours. The goal of EGDT was set for PiCCO parameters (mean arterial pressure (MAP), urine output and cardiac index (CI), and central venous oxygen saturation (ScvO2). RESULTS: Piglets under RFR had lower urine output compared with NRFR, as well as lower total fluid volume (P<0.05). EVLW was decreased in ARDSp+RFR and NRFR, as well as in ARDSexp+RFR, but EVLW increased in ARDSexp+NRFR (P<0.05). PaO2/FiO2 decreased in ARDSp using both methods, but was higher with RFR (P<0.05), and was increased in ARDSexp+RFR. Other pulmonary indicators were comparable. The anti-inflammatory cytokines IL-10 and LXA4 were increased in ARDSexp after RFR (P<0.05), but not in the other groups. CONCLUSIONS: RFR led to better oxygenation in ARDSp and ARDSexp compared with NRFR, but fluid restriction improved oxygenation in ARDSexp only.

Total hip arthroplasty with subtrochanteric femoral shortening osteotomy for high hip dislocation.

OBJECTIVE: To evaluate the outcomes of total hip arthroplasty (THA) with subtrochanteric femoral shortening osteotomy for high hip dislocation. METHODS: In this retrospective study, the results of 24 primary THAs with acetabular reconstruction and subtrochanteric femoral shortening osteotomy in 21 patients with high hip dislocation were evaluated. The acetabula were reconstructed with cemented or uncemented cups and bone grafting. Transverse subtrochanteric femoral shortening osteotomies were applied and the osteotomy sites treated by bone grafting and cable fixation. Assessment was by Hip Harris scores and radiographic evaluation. RESULTS: The mean follow-up time was 42 months (18-108 months), three cases being lost to follow-up 18-27 months postoperatively. The HHS improved from 47.5 ± 8.7 to 88.5 ± 3.1. The mean length of femoral segments removed was 2.5 ± 0.8 cm (range, 1.0-4.5 cm) and mean acetabular inclination 43° ± 5° (range, 31°-54°). Caudalization of the femoral head center was 3.2 ± 3.0 mm (range, -3 to 12 mm) and lateralization 4.0 ± 4.0 mm (range, -9 to 11 mm). Mean greater trochanter height relative to theoretical hip center was 5.2 ± 1.0 cm (range, 3.5-7.1 cm) preoperatively and 0.2 ± 0.6 cm (range, -0.9 to 1.2 cm) postoperatively. Intraoperative trochanteric fractures occurred in three cases and sciatic nerve palsy in one. CONCLUSION: THA with subtrochanteric femoral shortening osteotomy is an effective technique for treating high hip dislocation. Its advantages include improvement in limb imbalance and decreased risk of sciatic nerve injury.

A-770041 reverses paclitaxel and doxorubicin resistance in osteosarcoma cells.

BACKGROUND: Reversing multidrug resistance (MDR) has been an important goal for clinical and investigational oncologists. In the last few decades, significant effort has been made to search for inhibitors to reverse MDR by targeting ATP-binding cassette (ABC) transporters (Pgp, MRP) directly, but these efforts have achieved little clinical success. Protein kinases play important roles in many aspects of tumor cell growth and survival. Combinations of kinase inhibitors and chemotherapeutics have been observed to overcome cancer drug resistance in certain circumstances. METHODS: We screened a kinase specific inhibitor compound library in human osteosarcoma MDR cell lines to identify inhibitors that were capable of reversing chemoresistance to doxorubicin and paclitaxel. RESULTS: We identified 18 small molecules that significantly increase chemotherapy drug-induced cell death in human osteosarcoma MDR cell lines U-2OSMR and KHOSR2. We identified A-770041 as one of the most effective MDR reversing agents when combined with doxorubicin or paclitaxel. A-770041 is a potent Src family kinase (Lck and Src) inhibitor. Western blot analysis revealed A-770041 inhibits both Src and Lck activation and expression. Inhibition of Src expression in U-2OSMR and KHOSR2 cell lines using lentiviral shRNA also resulted in increased doxorubicin and paclitaxel drug sensitivity. A-770041 increases the intracellular drug accumulation as demonstrated by calcein AM assay. CONCLUSIONS: These results indicate that small molecule inhibitor A-770041 may function to reverse ABCB1/Pgp-mediated chemotherapy drug resistance. Combination of Src family kinase inhibitor with regular chemotherapy drug could be clinically effective in MDR osteosarcoma.

MicroRNA-21 controls the development of osteoarthritis by targeting GDF-5 in chondrocytes.

Osteoarthritis is a common cause of functional deterioration in older adults and is an immense burden on the aging population. Altered chondrogenesis is the most important pathophysiological process involved in the development of osteoarthritis. However, the molecular mechanism underlying the regulation of chondrogenesis in patients with osteoarthritis requires further elucidation, particularly with respect to the role of microRNAs. MiR-21 expression in cartilage specimens was examined in 10 patients with knee osteoarthritis and 10 traumatic amputees. The effect of miR-21 on chondrogenesis was also investigated in a chondrocyte cell line. The effect of miR-21 on the expression of growth differentiation factor 5 (GDF-5) was further assessed by luciferase reporter assay and western blot. We found that endogenous miR-21 is upregulated in osteoarthritis patients, and overexpression of miR-21 could attenuate the process of chondrogenesis. Furthermore, we identified GDF-5 as the direct target of miR-21 during the regulation of chondrogenesis. Our data suggest that miR-21 has an important role in the pathogenesis of osteoarthritis and is a potential therapeutic target.

Cyclin-dependent kinase 11 (CDK11) is crucial in the growth of liposarcoma cells.

Liposarcoma is the second most common soft tissue sarcoma in adults, but treatment options have been quite limited thus far. In this study, we investigated the functional and therapeutic relevance of cyclin-dependent kinase 11 (CDK11) as a putative target in liposarcoma. CDK11 knockdown by synthetic siRNA or lentiviral shRNA decreased cell proliferation, and induced apoptosis in liposarcoma cells. Moreover, CDK11 knockdown enhances the cytotoxic effect of doxorubicin to inhibit cell growth in liposarcoma cells. These findings suggest that CDK11 is critical for the growth and proliferation of liposarcoma cells. CDK11 may be a promising therapeutic target for the treatment of liposarcoma patients.

Tissue microarray immunohistochemical detection of brachyury is not a prognostic indicator in chordoma.

Brachyury is a marker for notochord-derived tissues and neoplasms, such as chordoma. However, the prognostic relevance of brachyury expression in chordoma is still unknown. The improvement of tissue microarray technology has provided the opportunity to perform analyses of tumor tissues on a large scale in a uniform and consistent manner. This study was designed with the use of tissue microarray to determine the expression of brachyury. Brachyury expression in chordoma tissues from 78 chordoma patients was analyzed by immunohistochemical staining of tissue microarray. The clinicopathologic parameters, including gender, age, location of tumor and metastatic status were evaluated. Fifty-nine of 78 (75.64%) tumors showed nuclear staining for brachyury, and among them, 29 tumors (49.15%) showed 1+ (<30% positive cells) staining, 15 tumors (25.42%) had 2+ (31% to 60% positive cells) staining, and 15 tumors (25.42%) demonstrated 3+ (61% to 100% positive cells) staining. Brachyury nuclear staining was detected more frequently in sacral chordomas than in chordomas of the mobile spine. However, there was no significant relationship between brachyury expression and other clinical variables. By Kaplan-Meier analysis, brachyury expression failed to produce any significant relationship with the overall survival rate. In conclusion, brachyury expression is not a prognostic indicator in chordoma.