MiR-383 sensitizes osteosarcoma cells to bortezomib treatment via down-regulating PSMB5.

BACKGROUND: Proteasome inhibition is a promising strategy for cancer therapy. Bortezomib, which primarily targets the chymotrypsin-like activity of PSMB5, has demonstrated efficacy in various tumors. However, there is variable sensitivity to bortezomib, which could be attributed, in part, to variations in the expression of proteasome subunits. METHODS AND RESULTS: In this study, we investigated whether miR-383 affects the expression of proteasome subunits in osteosarcoma (OS) cells, and if so, whether OS cells display differential sensitivity to bortezomib concerning miR-383 expression. We detected a decreased miR-383 expression in OS cells and tissues. Then we found a negative correlation between the cytotoxicity of bortezomib and the expression level of the proteasome 20S core particle subunit ß5 (PSMB5). Intriguingly, we identified PSMB5 as a direct target of miR-383. Increased expression of miR-383 resulted in decreased PSMB5 expression and increased sensitivity to bortezomib in OS cells. CONCLUSIONS: In summary, our findings present the initial comprehensive analysis of the function of miR-383 in OS. The outcomes indicate that miR-383 may augment the anticancer effect of bortezomib through PSMB5 repression, offering a novel therapeutic approach in OS and a fresh pathway for proteasome regulation.

SIX4 upregulates IDH1 and metabolic reprogramming to promote osteosarcoma progression.

Metabolism reprogramming plays an important role in tumorigenesis and osteosarcoma metastasis. Sine oculis homeobox 4 (SIX4) is reported to be a key transcription factor that is involved in glycolysis reprogramming of cancer cells. However, the role of SIX4 in osteosarcoma progression remains unknown. The expression profile of SIX4 in OS was evaluated in surgery samples of osteosarcoma patients. Functional studies were performed in vitro and in vivo. We found that SIX4 is significantly overexpressed in osteosarcoma and related to the undesirable prognosis of osteosarcoma patients. SIX4 promotes progression of osteosarcoma via upregulating isocitrate dehydrogenase 1 (IDH1), which provides novel prognostic biomarkers and promising therapeutic targets for osteosarcoma patients.

Nuclear receptor coactivator 3 transactivates proinflammatory cytokines in collagen-induced arthritis.

Rheumatoid arthritis (RA) is an autoimmune disorder in which the immune system mistakenly attacks joints. The molecular mechanisms underlying RA pathology are still under investigation. In this study, we discovered overexpression of nuclear receptor coactivator 3 (NCOA3) in the joint tissues of type II collagen-induced arthritis (CIA) mice, an important autoimmune model of human RA. Administration of two NCOA3 inhibitors, gossypol (GSP) and SI-2 hydrochloride (SHC), significantly alleviated inflammation and improved the outcomes of CIA mice. In vivo and in vitro experiments revealed that NCOA3 assembled a transcriptional complex with a histone acetyltransferase p300 and two subunits of nuclear factor kappa B (NF-κB). This complex specifically controlled the expression of proinflammatory cytokine genes by binding to their promoters. Knockdown of NCOA3 or in vitro treatments with GSP and SHC impaired the assembly of NCOA3-p300-NF-κB complex and decreased the expression of proinflammatory cytokine genes. Taken together, our results demonstrated that NCOA3 acts as a mediator of proinflammatory cytokine genes in CIA mice and that inhibition of the NCOA3-p300-NF-κB complex may represent a new avenue for improving RA outcomes.

Prevalence and Risk Factors of Osteoporosis in a Chinese Population: A Cross-Sectional Study in Xi'an, Shaanxi Province, China.

BACKGROUND Osteoporosis is a systemic chronic disease characterized by bone mineral density (BMD) reduction. This study aimed to assess the prevalence of osteoporosis and fracture risks in northwestern China and investigate the related anthropometric risk factors. MATERIAL AND METHODS Between July 2022 and August 2022, 1429 participants (1295 females, 134 males) with measured BMD were recruited to participate in this cross-sectional study. Data on height, weight, and T score were collected. Spearman's correlation and multiple linear regression analysis were used to investigate the relationships between various demographic factors and BMD and the 10-year risk of major osteoporotic fracture (MO) and hip fracture (HP). RESULTS The overall prevalence of osteoporosis in northwest China was 42.34%, with 44.56% in females and 20.90% in males. Age negatively affects females' T scores (r=-0.304, P<0.05), and height positively influences both sexes' T scores (r=0.059 P<0.05). Age (r=0.148, P<0.05) and height were positive predictors of MO (r=0.027, P<0.05), while weight was a negative predictor (r=-0.035, P<0.05). The conclusion for HP was consistent with that of MO, except for the T score, which was a positive predictor of HP (r=0.014, P<0.05). CONCLUSIONS The prevalence of osteoporosis in northeast China is high. The association between anthropometric parameters and osteoporosis in adults in northwest China is different between sexes.

S100A10 regulates tumor necrosis factor alpha-induced apoptosis in chondrocytes via the reactive oxygen species/nuclear factor-kappa B pathway.

Aberrant chondrocyte apoptosis and inflammation are the most critical causes of osteoarthritis (OA) development. This study was designed to demonstrate the relationship between S100A10 and OA. In this study, S100A10 was overexpressed or silenced in rat chondrocytes. Cell viability, apoptosis, reactive oxidative species (ROS), and calcium ion detection were assessed using Cell Counting Kit-8 assay and flow cytometry. The levels of key oxidation-related enzymes and tumor necrosis factor-alpha (TNF-α) were quantified using enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, and Western blotting. S100A10 was highly expressed in patients with OA and positively correlated with TNF-α level. Knockdown of S100A10 effectively counteracted TNF-α-induced ROS level, apoptosis, and calcium level and associated with decreased inflammation-related metalloproteinase 1 (MMP1), MMP13, and nuclear necrosis factor-kappa B (NF-κB)-p65 and increased survivin and cytoplasmic NF-κB-p65. Overexpression of S100A10 had an effect similar to TNF-α, which was significantly counteracted by pyrrolidine dithiocarbamate, an NF-κB inhibitor, or verapamil, a calcium-channel blocker. S100A10 contributed to chondrocyte apoptosis through the ROS/NF-κB pathway. This study has established the relationship between S100A10 and the NF-κB pathway, thus providing novel perspectives for exploring S100A10 functions.

Tranexamic acid is beneficial for blood management of high tibial osteotomy: a randomized controlled study.

INTRODUCTION: The purpose of this study was to investigate whether TXA can effectively reduce blood loss after HTO and related complications and to evaluate its safety. MATERIALS AND METHODS: From March 2016 to March 2018, 100 patients who underwent medial opening wedge HTO in the Department of Orthopedics, the second affiliated hospital of xi'an jiaotong university, with an average age of 52.8 ± 3.2 years, were randomly divided into the TXA group (using intravenous TXA) and the control group (using the same amount of normal saline), with 50 patients in each group. The postoperative wound drainage volume, decrease in hemoglobin and hematocrit value, total blood loss, wound healing, blood transfusion, deep venous thrombosis (DVT) and pulmonary embolism (PE) were compared between the two groups. RESULTS: The drainage volume on the first postoperative day and the total drainage volume of the TXA group were significantly lower compared with those of the control group (145.7 vs 264.5 ml, 282.3 vs 413.2 ml, P < 0.05). The decreases in the hemoglobin and hematocrit values on the postoperative first, second and fifth days were lower in the TXA group than those in the control group (1.4 VS 3.5, 2.6 vs 3.3, 1.9 vs 2.9 g, P < 0.05; 3.3 vs 5.5, 5.0 vs 9.1, 3.8 vs 7.2%, P < 0.05), and the mean total blood loss was also lower in the TXA group than that in the control group (477.9 vs 834.6 ml, P < 0.05). In the control group, 1 patient had wound hematoma requiring additional paracentesis and pressure dressing, 1 patient had superficial wound infection requiring additional debridement, and 1 patient had postoperative blood transfusion compared to none in the TXA group (P > 0.05). There was no symptomatic DVT or PE in either of the groups. CONCLUSION: Intravenous TXA can effectively and safely reduce blood loss and bleeding-related complications after HTO and was beneficial for the blood management of HTO.

The Relationship Between Body Mass Index and Bone Mineral Density: A Mendelian Randomization Study.

Body mass index (BMI) is closely associated with bone mineral density (BMD) in both men and women. However, the relationship between BMI and BMD varies according to different studies. Using SNPs strongly associated with BMI in 336,107 individuals, we conducted a two-sample Mendelian randomization study to identify whether and to what extent BMD at different skeletal sites was affected by BMI. A power calculation was also performed. We found that BMI may causally increase lumbar BMD (ß 0.087; 95% CI 0.025 to 0.149; P = 0.006) and heel calcaneus BMD (ß 0.120; 95% CI 0.082 to 0.157; P = 1 × 10-7). The associations of BMI with forearm and femoral neck BMD were not statistically significant. Our study suggested that higher BMI plays a causal role in increasing BMD and the effects are similar across the skeleton. BMI was causally and positively associated with lumbar and heel calcaneus BMD. However, no statistically significant effects were observed for BMI on femoral neck or forearm BMD.

Fluid shear stress induces Runx-2 expression via upregulation of PIEZO1 in MC3T3-E1 cells.

Mechanically induced biological responses in bone cells involve a complex biophysical process. Although various mechanosensors have been identified, the precise mechanotransduction pathway remains poorly understood. PIEZO1 is a newly discovered mechanically activated ion channel in bone cells. This study aimed to explore the involvement of PIEZO1 in mechanical loading (fluid shear stress)-induced signaling cascades that control osteogenesis. The results showed that fluid shear stress increased PIEZO1 expression in MC3T3-E1 cells. The fluid shear stress elicited the key osteoblastic gene Runx-2 expression; however, PIEZO1 silencing using small interference RNA blocked these effects. The AKT/GSK-3ß/ß-catenin pathway was activated in this process. PIEZO1 silencing impaired mechanically induced activation of the AKT/GSK-3ß/ß-catenin pathway. Therefore, the results demonstrated that MC3T3-E1 osteoblasts required PIEZO1 to adapt to the external mechanical fluid shear stress, thereby inducing osteoblastic Runx-2 gene expression, partly through the AKT/GSK-3ß/ß-catenin pathway.

Neuroprotection of melatonin on spinal cord injury by activating autophagy and inhibiting apoptosis via SIRT1/AMPK signaling pathway.

The effect of melatonin (MT) on spinal cord injury (SCI) has attracted increasing research attention. However, the specific role and molecular mechanism of MT on SCI have not been elucidated. An experiment was performed to investigate the effect and molecular mechanism of MT on the neuronal autophagy after SCI and its effect on the recovery of nerve function. The rats were randomly divided into four treatment groups: the SCI+MT+EX527 (SIRT1 inhibitor), SCI+MT, SCI, and sham operation groups. On the 14th day after SCI, MT significantly promoted the recovery of motor function in the hind limbs according to the results of Basso, Beattie, and Bresnahan scores. At the same time, MT treatment resulted in reduced activation of cleaved-caspase-3, cleaved-caspase-9, and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive neurons and increased the survival of motoneurons in the anterior horn of the spinal cord on the 14th day after SCI, which exerted its neuroprotection. Furthermore, western blot and immunofluorescence double staining were performed to verify the molecular mechanism of effect of MT on SCI, and results showed the significantly upregulated expressions of Beclin-1, light chain-3B, SIRT1, p-AMPK proteins in the spinal cord tissue of MT-treated rats on the 14th day after SCI, however, the effect of MT on autophagy was reversed by EX527 (SIRT1 inhibitor), which implied that MT activated autophagy via SIRT1/AMPK signaling pathway after SCI. Similarly, the neuroprotective effects of MT on SCI were also inhibited after the SIRT1/AMPK signaling pathway was suppressed by EX527. Taken together, these results suggest that MT inhibits the apoptosis and activates autophagy of nerve cells after SCI and ultimately exerts the neuroprotective effect by SIRT1/AMPK signaling pathway.

The modified cross-suture technique for unilateral pulled-out anchor during all-inside meniscal repair.

BACKGROUND: Meniscal repair has received increasing attention, but for inexperienced doctors, unilateral suture anchor pulling out may occur during all-inside meniscal repair, and the treatment outcome may be affected. When the errors happened intraoperatively, how to minimize the loss under guaranteeing of treatment effectiveness is a topic worth studying. PURPOSE: To explore the practicability and effectiveness of the modified cross-suture method for arthroscopic remediation of unilateral suture anchor pulling out of an all-inside meniscal repair system. METHODS: From May 2014 to May 2017, 28 patients diagnosed with injuries of the meniscus and anterior cruciate ligaments (ACL) from the First Department of Orthopaedics of the Second Affiliated Hospital of Xi'an Jiaotong University were enrolled in the study as the observation group, including 18 males and 10 females with an average age of 25.5 ± 2.3 years (range 18-42 years). All patients underwent ACL reconstruction concurrently. All meniscus injuries were repaired with an all-inside meniscal repair technique, and 1-3 needles of unilateral suture anchor pulling out occurred intraoperatively. The modified cross-suture method was used to remedy the error of anchor pulling out and to eventually complete an effective repair. Another 30 patients who underwent ACL reconstruction and all-inside meniscal concurrently without unilateral suture anchor pulling out, including 20 males and 10 females with an average age of 26.3 ± 1.9 years (range 19-45 years), were enrolled as the control group. During postoperative follow-up, range of motion, Lachman test and pivot shift test were performed during the physical examination. The clinical healing of the meniscus was evaluated according to the Barrett standard. The meniscus healing status was also confirmed with magnetic resonance imaging (MRI). The function of the knee joint was evaluated according to the IKDC, Lysholm and Tegner scores. RESULTS: Twenty-five patients in the observation group and 28 patients in the control group completed the follow-up, with an average follow-up of 18.4 ± 5.2 months. All operations were performed by the same surgeon. At the follow-up 1 year after the operation, the average knee ROM of the two groups was 125.2 ± 4.3 degrees and 124.7 ± 3.8 degrees, the clinical healing rate of the meniscus of the two groups was 92.0% (23/25) and 92.9% (26/28), the MRI healing rate of the menniscus of the two groups was 72.0% (18/25) and 71.4% (20/28), and the IKDC, Lysholm and Tegner scores of the two groups were 90.52 ± 2.8, 89.17 ± 3.1, and 6.81 ± 1.7 and 91.42 ± 1.9, 90.32 ± 3.4, and 7.02 ± 1.4, respectively. The differences were not statistically significant (P > 0.05). CONCLUSIONS: The modified cross-suture method is practicable and effective for arthroscopic remediation of unilateral suture anchor pulling out in an all-inside meniscal repair system.

Effects of delayed hip replacement on postoperative hip function and quality of life in elderly patients with femoral neck fracture.

BACKGROUND: For various reasons, some elderly patients with femoral neck fracture undergo delayed surgical treatment. There is little information about the effect of delayed treatment on postoperative hip function and quality of life. The aim of this study was to investigate the effect of delayed hip arthroplasty on hip function, quality of life, and satisfaction in patients with femoral neck fractures. METHODS: Forty-seven patients with femoral neck fracture and hip replacement delayed over 21 days served as the delayed group (D group). Patients with femoral neck fracture, matched 1:1 for age and sex, and hip replacement within 7 days served as the control group (C group). The Harris hip score (HHS) and health-related quality of life (HRQoL) were assessed before surgery and 3 months, 6 months and 1 year postoperatively. The satisfaction questionnaires were completed by the patients themselves at the last follow-up. RESULTS: The HHS in the C group was lower than that in the D group (32.64 ± 9.11 vs. 46.32 ± 9.88, P < 0.05) before surgery but recovered faster after surgery. The HHS in the D group was lower than that in the C group 1 year postoperatively (85.2 ± 3.80 vs. 89.8 ± 3.33, P < 0.05). The patients' quality of life changed similarly to their HHS. The HHS 1 year after surgery was related to the preoperative HHS in group D (rs = 0.521, P < 0.01). Patients in the D group showed significantly higher satisfaction scores than those in the C group (P < 0.05). CONCLUSIONS: Hip function in patients with femoral neck fracture surgery delayed over 21 days recovered more slowly than that in those who underwent surgery within 7 days. However, they were more satisfied with the surgery. Moderate hip movement to ameliorate the lower limb muscle atrophy was recommended for patients facing a temporary inability to undergo surgery.

Arthroscopic tri-pulley Technology reduction and internal fixation of pediatric Tibial Eminence fracture: a retrospective analysis.

BACKGROUND: Fixing a tibial eminence fracture with a tri-pulley is a new technique. The purpose of this study was to present the early clinical outcome of arthroscopic tri-pulley suture fixation for tibial eminence fractures in children. METHODS: Twenty-one pediatric patients with type II or type III anterior tibial eminence fractures were included in this retrospective study. All Patients underwent surgical fixation by tri-pulley technology and were followed up for at least 24 months. They were evaluated preoperatively and postoperatively by physical, X-ray, and computed tomography (CT) examination and subjectively with the International Knee Documentation Committee (IKDC), and Lysholm questionnaires. RESULTS: The patients included 12 males and 9 females; mean age, 12.5 years (range, 8 ~ 16 years). They were followed-up for a median of 27 months (range, 24 ~ 39 months). We did not find post-operative instability in any of the patients by physical examination. The KT-2000 difference of both knees decreased from 9.3 ± 1.2 mm preoperatively to 2.6 ± 0.8 mm 24 months postoperatively (P < 0.001); the IKDC subjective knee evaluation score improved from 43.1 ± 13.2 preoperatively to 83.8 ± 6.3 postoperatively (P < 0.001); and Lysholm improved from 48.3 ± 6.21 to 87.1 ± 9.8 (P < 0.001). No unhealed fractures or epiphyseal damage were reported in the postoperative X-ray and CT. CONCLUSIONS: Arthroscopic tri-pulley fixation technology may provide a suitable technique for repair of tibial eminence fractures in skeletally immature patients. LEVEL OF EVIDENCE: Case series; Level of evidence IV.

A Method of Accurate Bone Tunnel Placement for Anterior Cruciate Ligament Reconstruction Based on 3-Dimensional Printing Technology: A Cadaveric Study.

PURPOSE: To explore a method of bone tunnel placement for anterior cruciate ligament (ACL) reconstruction based on 3-dimensional (3D) printing technology and to assess its accuracy. METHODS: Twenty human cadaveric knees were scanned by thin-layer computed tomography (CT). To obtain data on bones used to establish a knee joint model by computer software, customized bone anchors were installed before CT. The reference point was determined at the femoral and tibial footprint areas of the ACL. The site and direction of the bone tunnels of the femur and tibia were designed and calibrated on the knee joint model according to the reference point. The resin template was designed and printed by 3D printing. Placement of the bone tunnels was accomplished by use of templates, and the cadaveric knees were scanned again to compare the concordance of the internal opening of the bone tunnels and reference points. RESULTS: The twenty 3D printing templates were designed and printed successfully. CT data analysis between the planned and actual drilled tunnel positions showed mean deviations of 0.57 mm (range, 0-1.5 mm; standard deviation, 0.42 mm) at the femur and 0.58 mm (range, 0-1.5 mm; standard deviation, 0.47 mm) at the tibia. CONCLUSIONS: The accuracy of bone tunnel placement for ACL reconstruction in cadaveric adult knees based on 3D printing technology is high. CLINICAL RELEVANCE: This method can improve the accuracy of bone tunnel placement for ACL reconstruction in clinical sports medicine.

HSYA alleviates secondary neuronal death through attenuating oxidative stress, inflammatory response, and neural apoptosis in SD rat spinal cord compression injury.

BACKGROUND: Hydroxysafflor yellow A (HSYA) is a major active component of yellow pigment extracted from safflowers; this compound possesses potent neuroprotective effects both in vitro and in vivo. However, underlying mechanism of HSYA is not fully elucidated. The present study investigated the protective effects of HSYA in rat spinal cord compression injury model and related mechanisms involved. METHODS: Sprague-Dawley rats were divided as Sham, Control, and HSYA groups (n = 30 per group). Spinal cord injury (SCI) model was induced by application of vascular clips (force of 50 g, 1 min) to the dura at T9-T10 level of vertebra. Injured animals were administered with either HSYA (8 mg/kg at 1 and 6 h after injury, then 14 mg/kg, for a total of 7 days at 24-h time intervals) or equal volume of saline by intraperitoneal injection. RESULTS: From this experiment, we discovered that SCI in rats resulted in severe trauma, which is characterized by tissue damage, lipid peroxidation, neutrophil infiltration, inflammation mediator release, and neuronal apoptosis. However, HSYA treatment significantly reduced the following: (1) degree of tissue injury (histological score) and edema; (2) neutrophil infiltration (myeloperoxidase activity); (3) oxidative stress (superoxide dismutase, malondialdehyde, and nitric oxide); (4) pro-inflammatory cytokine expression (tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2); (5) nuclear factor-κB activation; (6) apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling staining and cysteine-aspartic protease-3 activity). Moreover, in a separate set of experiments, we clearly demonstrated that HSYA treatment significantly ameliorated recovery of limb function (as evaluated by Basso, Beattie, and Bresnahan behavioral recovery scores). CONCLUSIONS: Treatment with HSYA restrains development of oxidative stress, inflammation response, and apoptotic events associated with SCI of rats, demonstrating that HSYA is a potential neuroprotectant for human SCI therapy.

Melatonin Inhibits Neural Cell Apoptosis and Promotes Locomotor Recovery via Activation of the Wnt/ß-Catenin Signaling Pathway After Spinal Cord Injury.

The spinal cord is highly sensitive to spinal cord injury (SCI) by external mechanical damage, resulting in irreversible neurological damage. Activation of the Wnt/ß-catenin signaling pathway can effectively reduce apoptosis and protect against SCI. Melatonin, an indoleamine originally isolated from bovine pineal tissue, exerts neuroprotective effects after SCI through activation of the Wnt/ß-catenin signaling pathway. In this study, we demonstrated that melatonin exhibited neuroprotective effects on neuronal apoptosis and supported functional recovery in a rat SCI model by activating the Wnt/ß-catenin signaling pathway. We found that melatonin administration after SCI significantly upregulated the expression of low-density lipoprotein receptor related protein 6 phosphorylation (p-LRP-6), lymphoid enhancer factor-1 (LEF-1) and ß-catenin protein in the spinal cord. Melatonin enhanced motor neuronal survival in the spinal cord ventral horn and improved the locomotor functions of rats after SCI. Melatonin administration after SCI also reduced the expression levels of Bax and cleaved caspase-3 in the spinal cord and the proportion of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) positive cells, but increased the expression level of Bcl-2. These results suggest that melatonin attenuated SCI by activating the Wnt/ß-catenin signaling pathway.

Albumin's Influence on Carprofen Enantiomers-Hymecromone Interaction.

Hymecromone is an important coumarin drug, and carprofen is one of the most important nonsteroidal antiinflammatory drugs (NSAIDs). The present study aims to determine the influence of bovine serum albumin (BSA) on the carprofen-hymecromone interaction. The inhibition of carprofen enantiomers on the UDP-glucuronosyltransferase (UGT) 2B7-catalyzed glucuronidation of hymecromone was investigated in the UGTs incubation system with and without BSA. The inhibition capability of increased by 20% (P < 0.001) of (R)-carprofen after the addition of 0.5% BSA in the incubation mixture. In contrast, no significant difference was observed for the inhibition of (S)-carprofen on UGT2B7 activity in the absence or presence of 0.5% BSA in the incubation system. The Lineweaver-Burk plot showed that the intersection point was located in the vertical axis, indicating the competitive inhibition of (R)-carprofen on UGT2B7 in the incubation system with BSA, which is consistent with the inhibition kinetic type of (R)-carprofen on UGT2B7 in the incubation system without BSA. Furthermore, the second plot using the slopes from the Lineweaver-Burk versus the concentrations of (R)-carprofen showed that the fitting equation was y=39.997x+50. Using this equation, the inhibition kinetic parameter was calculated to be 1.3 µM. For (S)-carprofen, the intersection point was located in the horizontal axis in the Lineweaver-Burk plot for the incubation system with BSA, indicating the noncompetitive inhibition of (S)-carprofen on the activity of UGT2B7. The fitting plot of the second plot was y=24.6x+180, and the inhibition kinetic parameter was 7.3 µM. In conclusion, the present study gives a short summary of BSA's influence on the carprofen enantiomers-hymecromone interaction, which will guide the clinical application of carprofen and hymecromone.

Factors relating to curve progression in female patients with adolescent idiopathic scoliosis treated with a brace.

PURPOSE: One single factor cannot by itself predict curve progression accurately. The aim of this study is to determine multiple related factors in predicting the progression of scoliosis in girls with adolescent idiopathic scoliosis (AIS) treated with bracing. METHODS: Eighty-nine female patients with AIS treated with a brace were reviewed. A series of parameters were consecutively measured and documented during the period of follow-up. Curve behavior between the first visit and final follow-up was analyzed. Several different parameters which may contribute to progression of curve were selected by a logistic regression analysis. RESULTS: Mean age of patients at the first visit was 13.6 (10-16) years. The patients were followed for 12-72 months (mean 24.8 months). At the last visit, 21 patients (23.60 %) had curve progression more than 5°. After performing a logistic regression analysis, Risser sign less than two, the magnitude of the major curve at pre-brace greater than 35°, apical vertebral rotation beyond grade III, and the spinal length increasing larger than 20 mm in 1 year were found to be factors which predict the progression of more than 5°. CONCLUSIONS: This study suggests that Risser sign, the magnitude of the major curve at pre-brace, apical vertebral rotation, and the spinal length increasing velocity are important factors to predict progression in the girls with AIS. Risser sign cannot predict the progression of scoliosis accurately unless combined with other related parameters.

Apoptosis associated with Wnt/ß-catenin pathway leads to steroid-induced avascular necrosis of femoral head.

BACKGROUND: The objective of the current study was to establish a rat model to investigate apoptosis in steroid-induced femoral head osteonecrosis occurring via the Wnt/ß-catenin pathway. METHODS: Male Sprague-Dawley (SD) rats were randomly divided into a control group (group A), model group (group B) and sFRP1 group (group C), each consisting of 24 rats, and the rats were intravenously injected with LPS (10 µg/kg body weight). After 24 h, three injections of MPS (20 mg/kg body weight) were administered intramuscularly at 24-h intervals. The rats in group C were injected intramuscularly with 1 µg/kg sFRP1 protein per day for 30 days, beginning at the time of the first MPS administration. The group A rats were fed and housed under identical conditions but received saline injection. All animals were sacrificed at weeks 2, 4 and 8 from the first MPS injection. Histopathological staining was preformed to evaluated osteonecrosis. Apoptosis was detected via quantitative terminal deoxynucleotidyl transferase (TdT) deoxyuridine triphosphate nick-end labelling (TUNEL) staining, caspase-3 activity assay, and detection of Bcl-2 and Bax protein expression by immunohistochemistry and Western blotting. Wnt/ß-catenin pathway signalling molecules, including activated ß-catenin and c-Myc, were detected by immunohistochemistry and Western blotting. RESULTS: Typical osteonecrosis was observed in groups B and C. Apoptosis gradually increased with increasing time in both groups B and C. More severe osteonecrosis and apoptosis were observed in group C compared with group B. The expression levels of caspase-3 and Bax were higher while that of Bcl-2 was lower in group C compared with group B. The expression levels of activated ß-catenin and c-Myc gradually decreased with increasing time in both groups B and C, and they were lower in group C compared with group B. CONCLUSIONS: The Wnt/ß-catenin pathway is involved in the pathogenesis of early stage SANFH, as we have demonstrated in an SANFH rat model, and it may act through the regulation of c-Myc, which affects the cell cycle and cell apoptosis.

Comparative study of serum proteomes in Legg-Calve-Perthes disease.

BACKGROUND: Legg-Calve-Perthes Disease (LCPD) is an idiopathic osteonecrosis of the developing femoral head complicated by pain and disability of the hip joint. To date, the pathological mechanisms of LCPD are not well-known. This study screened the changes in serum protein expression in patients with LCPD. METHODS: Age- and sex-matched serum samples from 10 control subjects and 10 patients with LCPD were compared using the isobaric tags for relative and absolute quantification (iTRAQ) technique. Gene ontology analyses, KEGG pathway and functional network analyses were performed. Proteins of interest with large differences in expression, S100-A8, alpha-1-acid glycoprotein 1, haptoglobin and apolipoprotein E, were compared by western blotting. RESULTS: The disease/control ratios showed 26 proteins were significantly differentially expressed (all p < 0.05). Including higher abundances of complement factor H (1.44), complement C4-B (1.45), isocitrate dehydrogenase [NAD] subunit alpha (2.7) alpha-1-acid glycoprotein 1 (1.87), heptoglobin (1.53) and Ig lambda-2 chain C regions (1.46), and lower levels of apolipoprotein E (0.50), apolipoprotein F (0.60), apolipoprotein C-III (0.69), S100-A8 (0.73), S100-A9 (0.75) and prothrombin (0.77) in LCPD than in controls. The alpha-1-acid glycoprotein 1 and haptoglobin increases, and apolipoprotein E and S100-A8 decreases were confirmed by western blot. KEGG pathway analysis revealed these proteins were related to the complement and coagulation cascades, Staphylococcus aureus infection, PPAR signaling, fat digestion and absorption, and vitamin digestion and absorption. Functional network analysis suggested that the proteins were involved in lipid regulation. CONCLUSIONS: The complement and coagulation cascades, and abnormal lipid metabolism may be involved in the pathogenesis of LCPD.

Sciatic nerve course in adult patients with unilateral developmental dysplasia of the hip: implications for hip surgery.

BACKGROUND: Sciatic nerve injury is a disastrous adverse complication of surgery and can cause debilitating pain, functional impairment and poor quality of life. Patients with developmental dysplasia of the hip (DDH) have a high incidence of sciatic nerve injury after total hip arthroplasty (THA). A better understanding of the course of the sciatic nerve in patients with DDH may help minimise the risk of sciatic nerve injury after THA. METHODS: A total of 35 adult patients with unilateral DDH were enrolled in this retrospective study. We reviewed the patients' computed tomography (CT) scans, which included the area from the iliac crest to below the lesser trochanter. The distance between the sciatic nerve and regional anatomic landmarks in four different sections on CT scans was measured to identify the course of the sciatic nerve. RESULTS: The distance from the sciatic nerve to the spine's midline was shorter on the affected side than on the healthy side (p < 0.05); the same difference was also detected in the distance to the ilium/ischium outside the true pelvis (p < 0.05). The distance to the greater trochanter was longer on the affected side (p < 0.05). However, the two sides showed no significant difference in the distance from the sciatic nerve to the lesser trochanter (p > 0.05). CONCLUSIONS: For patients with unilateral DDH, the sciatic nerve was located near the ischium and ilium but relatively far from the femur of the affected hip joint, compared to its location on the healthy side. These findings reveal that sciatic nerve becomes shorter in the affected low-limb and is relatively unlikely to be directly injuried using the posterolateral approach in patients with unilateral DDH.