Elevated level of circulating calprotectin correlates with severity and high mortality in patients with COVID-19.

BACKGROUND: Patients with coronavirus disease-2019 (COVID-19) are characterized by hyperinflammation. Calprotectin (S100A8/S100A9) is a calcium- and zinc-binding protein mainly secreted by neutrophilic granulocytes or macrophages and has been suggested to be correlated with the severity and prognosis of COVID-19. AIM: To thoroughly evaluate the diagnostic and prognostic utility of calprotectin in patients with COVID-19 by analyzing relevant studies. METHODS: PubMed, Web of Science, and Cochrane Library were comprehensively searched from inception to August 1, 2023 to retrieve studies about the application of calprotectin in COVID-19. Useful data such as the level of calprotectin in different groups and the diagnostic efficacy of this biomarker for severe COVID-19 were extracted and aggregated by using Stata 16.0 software. RESULTS: Fifteen studies were brought into this meta-analysis. First, the pooled standardized mean differences (SMDs) were used to estimate the differences in the levels of circulating calprotectin between patients with severe and non-severe COVID-19. The results showed an overall estimate of 1.84 (95% confidence interval [CI]: 1.09-2.60). Diagnostic information was extracted from 11 studies, and the pooled sensitivity and specificity of calprotectin for diagnosing severe COVID-19 were 0.75 (95% CI: 0.64-0.84) and 0.88 (95% CI: 0.79-0.94), respectively. The AUC was 0.89 and the pooled DOR was 18.44 (95% CI: 9.07-37.51). Furthermore, there was a strong correlation between elevated levels of circulating calprotectin and a higher risk of mortality outcomes in COVID-19 patients (odds ratio: 8.60, 95% CI: 2.17-34.12; p < 0.1). CONCLUSION: This meta-analysis showed that calprotectin was elevated in patients with severe COVID-19, and this atypical inflammatory cytokine might serve as a useful biomarker to distinguish the severity of COVID-19 and predict the prognosis.

Efficacy and safety of extracorporeal shockwave therapy in chronic low back pain: a systematic review and meta-analysis of 632 patients.

BACKGROUND: Extracorporeal shock wave therapy (ESWT) has been widely used for pain control in musculoskeletal disorders. Whether ESWT can relieve chronic low back pain (CLBP) and improve lumbar function is still unclear. Therefore, we conducted a meta-analysis of relevant studies to comprehensively analyse and determine the efficacy and safety of ESWT for chronic low back pain. METHODS: Four databases were systematically searched for randomized controlled trials (RCTs) on ESWT for CLBP. The quality of the included studies was evaluated according to Cochrane systematic review criteria, relevant data were extracted, and meta-analysis was performed using RevMan 5.4 software. The primary outcomes were pain intensity, disability status, and mental health. The data were expressed as standardized mean differences (SMD) or weighted mean difference (WMD) and 95% confidence intervals (CI). Heterogeneity was assessed using the I2 statistic. If I2 ≥ 50%, a random effects model was applied; otherwise, a fixed effects model was used. RESULTS: Twelve RCTs involving 632 patients were included in this meta-analysis. The ESWT group reported significantly more pain relief than the control group at 4 weeks (WMD = - 1.04; 95% CI = - 1.44 to - 0.65; P < 0.001) and 12 weeks (WMD = - 0.85; 95% CI = - 1.30 to - 0.41; P < 0.001). Regarding the dysfunction index, ESWT led to significant improvement in lumbar dysfunction compared with the control group at 4 weeks (WMD = - 4.22; 95% CI = - 7.55 to - 0.89; P < 0.001) and 12 weeks (WMD = - 4.51; 95% CI = - 8.58 to - 0.44; P = 0.03). For mental health, there was no significant difference between the ESWT group and the control group after 4 weeks of intervention (SMD = 1.17; 95% CI = - 0.10 to 2.45; P = 0.07). CONCLUSION: This systematic review and meta-analysis found that ESWT provided better pain relief and improved lumbar dysfunction compared with the other interventions included, and no serious adverse effects were found. There was no significant effect of ESWT on the mental health of patients, but we hope to obtain more RCTs for further analysis in the future. Based on the pooled results, we suggest that ESWT is effective and safe for treating chronic low back pain.

Non-coding RNAs in ossification of the posterior longitudinal ligament.

Ossification of the posterior longitudinal ligament (OPLL) is a kind of disease that involves a variety of factors leading to ectopic bone deposition of the spinal ligament. Although the detailed mechanism is not clear, genetic factors play important roles in the development of this disease. Noncoding RNA (ncRNA) refers to an RNA molecule that is not translated into a protein but participates in the regulation of gene expression. Functionally important types of ncRNA associated with OPLL include long noncoding RNA, microRNA, and circular RNA. We listed the differentially expressed ncRNAs in OPLL patients and normal controls to find the ncRNAs most relevant to the pathogenesis of the disease. The potential regulatory networks of ncRNA in OPLL cells were analyzed based on their most abundant signal transduction pathway data. The analysis of the highly connected ncRNAs in the regulatory network suggests that they play an important role in OPLL. These findings provide new directions for the study of OPLL pathogenesis and therapeutic targets. In this paper, we reviewed and analyzed the literature on ncRNAs in OPLL published in recent years, aiming to help doctors better understand and treat this disease.

The tumor suppressive role of TIMP3 in the human osteosarcoma cells.

BACKGROUND: Tissue inhibitor of metalloproteinase 3 (TIMP3) regulates a variety of cellular activities such as proliferation, viability, apoptosis, and motility. Functional loss of TIMP3 is reported in several human cancers. However, its role in osteosarcoma (OS) remains largely unclear. METHODS: In this study, we explored the mechanism underlying the modulation of TIMP3 in the growth and aggressiveness of U2OS and 143B human OS cells at both cellular and molecular levels. RESULTS: Our results show that overexpression of TIMP3 inhibits endogenous MMP activity and represses a series of oncogenic phenotypes of tumor cells independent of MMP inhibition, including reduced proliferation and survival, induced apoptosis, as well as improved sensitivity of tumor cells in response to cisplatin chemotherapy. TIMP3 overexpression also suppresses tumor cell invasion via its MMP inhibitory capacity. Importantly, TIMP3 modulates tumor cell oncogenesis via its induction of PTEN and subsequent inactivation of the PI3K/AKT pathway. CONCLUSION: Our results suggest that TIMP3 is an oncosuppressor in human OS cells. Reactivation of TIMP3 function may be considered as a potential therapy for the treatment of this bone cancer.

The NF-κB pathway is critically implicated in the oncogenic phenotype of human osteosarcoma cells.

NF-κB is activated in a variety of human cancers. However, its role in osteosarcoma (OS) remains unknown. Here, we have elucidated the implication of NF-κB in the oncogenic phenotype of OS tumor cells. We reported that activation of NF-κB was a common event in the human OS. Inhibition of NF-κB using inhibitor Bay 11-7085 repressed proliferation, survival, migration, and invasion but increased apoptosis in 143B and MG63 OS cells, indicating that NF-κB is critically implicated in the oncogenesis of OS. Notably, Bay 11-7085 not only inactivated NF-κB but also reduced the phosphorylation of AKT via its induction of PTEN, suggesting the existence of a novel NF-κB/PTEN/PI3K/AKT axis. In vivo, Bay 11-7085 suppressed tumor growth in the bone by targeting NF-κB and AKT. Interestingly, combined treatment with Bay 11-7085 and the PI3K inhibitor, LY294002, triggered an augmented antitumor effect. Our results demonstrate that NF-κB potentiates the growth and aggressiveness of OS. Pharmacological inhibition of NF-κB represents a promising therapy for the treatment of OS.

Critical implication of the PTEN/PI3K/AKT pathway during BMP2-induced heterotopic ossification.

Heterotopic ossification (HO) is characterized by extraskeletal ossification in soft tissue. Thus far, there is a lack of effective drug therapy against HO. Loss of PTEN in osteoblasts has been reported to accumulate bone mass in skeletal development and promote fracture healing in association with the activation of the PI3K/AKT pathway. However, the role of the PTEN/PI3K/AKT signaling in HO pathogenesis remains unknown. The present study investigated the implication of this pathway during BMP2­induced osteogenic differentiation and ectopic bone formation. It was shown that overexpression of PTEN inhibited proliferation but stimulated apoptosis in mesenchymal pluripotent C3H10T1/2 cells. PTEN also inhibited BMP2­induced osteoblast differentiation, whereas BMP2 repressed PTEN expression and subsequently activated PI3K/AKT. The PI3K inhibitor, LY294002, blocked BMP2­induced osteoblastogenesis, suggesting that the PI3K/AKT pathway is critically required for BMP2 to initiate osteoblastogenesis. In vivo, implantation of BMP2 in muscle induced ectopic endochondral ossification. Strikingly, this bone­forming capacity was notably suppressed by the PI3K inhibitor LY294002. Hence, the results of the present study demonstrated that the PI3K/AKT signaling activity is indispensable for BMP2 to induce ectopic new bone. Targeting the PI3K/AKT pathway using inhibitor(s) may represent a potential molecular therapy for the treatment against HO.

The yield of sonication fluid culture for presumed aseptic loosening of orthopedic devices: a meta-analysis.

BACKGROUND: Sonication fluid culture is routinely conducted in patients with suspected orthopedic devicerelated infection (ORI). However, its value in the assessment of orthopedic devices that have explanted because of presumed aseptic loosening is still debatable. A meta-analysis was conducted to estimate the yield of sonication fluid culture in detecting the presence of microorganisms in orthopedic devices with presumed aseptic loosening, and to summarize the clinical characteristics and outcomes of these patients. METHODS: A meta-analysis was performed of peer-reviewed publications detailing the characteristics of patients whose orthopedic devices were explanted for presumed aseptic loosening and who underwent subsequent sonication fluid culture. Diagnostic data were extracted and pooled to estimate the yield of sonication fluid culture for detecting the presence of microorganisms with 95% confidence intervals (CI). RESULTS: Eight studies involving 421 patients were included in the meta-analysis analysis. The pooled results showed that sonication fluid culture had a yield of approximately 30% (95% CI: 20-41%) for identifying the presence of microorganisms in presumed aseptic loosening of orthopedic devices; this yield was higher than that of intraoperative tissue culture (22%, 95% CI: 8-41%) and aspirated fluid culture (13%, 95% CI: 7-21%). Sonication and vortexing for ≤5 min had a detection rate of 49% (95% CI: 43-55%), which exceeded that of >5 min. Coagulase-negative Streptococcus accounted for 74% (95% CI: 51-92%) of the isolated microorganisms. However, patients with positive microbiological results of sonication fluid culture and those with negative results showed similar outcomes after revision surgery. CONCLUSIONS: Colonization of low-virulent microorganisms may exist in a considerable number of patients with clinically presumed aseptic loosening of orthopedic devices. When this occurs, sonication (1-5 min at 40 kHz) of fluid culture could act as a sensitive diagnostic tool. However, the question of whether sonication fluid culture should be integrated into the routine treatment of loosened orthopedic devices requires further investigation.

Dkk1 acts as a negative regulator in the osteogenic differentiation of the posterior longitudinal ligament cells.

Ossification of the posterior longitudinal ligament (OPLL) is a spinal disorder characterized by progressive ectopic bone formation in the PLL of the spine. Dickkopf-1 (Dkk1) is a secreted inhibitor of the Wnt pathway that negatively regulates bone formation during skeletal development. However, whether Dkk1 impacts the pathogenesis of OPLL has not been reported. This study is to investigate the role of Dkk1 in the development of OPLL. Our results show that the serum levels of Dkk1 are decreased in OPLL patients compared with non-OPLL controls. The expression of Dkk1 is also reduced in OPLL ligament cells. Downregulation of Dkk1 in ligament cells is associated with activation of the Wnt/ß-catenin signaling, as indicated by stabilized ß-catenin and increased T-cell factor-dependent transcriptional activity. Functionally, Dkk1 exerts a growth-inhibitory effect by repressing proliferation but promoting apoptosis of ligament cells. Dkk1 also suppresses bone morphogenetic protein 2-induced entire osteogenic differentiation of ligament cells, and this suppression is mediated via its inhibition of the Wnt pathway. Our results demonstrate for the first time that Dkk1 acts as an important negative regulator in the ossification of the PLL. Targeting the Wnt pathway using Dkk1 may represent a potential therapeutic strategy for the treatment of OPLL.

Circular RNA circ_0011269 sponges miR-122 to regulate RUNX2 expression and promotes osteoporosis progression.

Circular RNAs (circRNAs) are a novel class of noncoding RNAs that are widely expressed in human disease. However, circRNAs expression profile and potential mechanism in osteoporosis pathogenesis remain to be further studied. In the present study, a total of 69 circRNAs were identified to be abnormally expressed in osteoporosis patient samples by microarray and bioinformatics analyses. We found that circ_0011269 was notably downregulated in osteoporosis (fold change, 3.94). By means of miRanda algorithm, we constructed the interaction network of circ_0011269-miRNAs in osteoporosis based on target binding and miR-122 was enrolled in the network. Dual-luciferase reporter assay verified the target relationship of miR-122 and circ_0011269/RUNX2. The expression of circ_0011269 and RUNX2 were gradually increased during osteogenic differentiation while miR-122 exhibited a decreased expression. Moreover, overexpression of circ_0011269 could promote RUNX2 expression and inhibit osteoporosis. In summary, this study found that circ_0011269 sponges miR-122 to regulate RUNX2 expression and promotes osteoporosis progression.

The utility of 18F-FDG PET and PET/CT in the diagnosis and staging of chondrosarcoma: a meta-analysis.

OBJECTIVE: Chondrosarcoma is the second most common primary bone sarcoma; however, unlike other tumors, the biopsy cannot easily make a definite diagnosis or predict the histological grade. This meta-analysis was performed to evaluate the utility of 18F-FDG PET and PET/CT to differentiate chondrosarcoma from benign cartilaginous lesions and to predict the histopathological grade of chondrosarcoma. MATERIAL AND METHODS: A comprehensive search was performed in three electronic databases including Medline/PubMed, the Cochrane Library and Embase to retrieve diagnostic studies evaluating the role of 18F-FDG PET or PET/CT for appraising the status of chondrosarcoma. Reference lists of related articles were also scrutinized manually. Useful data were extracted to calculate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), the summary receiver operating characteristic curve (sROC), and the area under the curve (AUC) of 18F-FDG PET or PET/CT in diagnosing chondrosarcoma, and pooled weighted mean differences (WMD) of maximum standardized uptake value (SUVmax) between different entities of cartilaginous neoplasms by using Stata 19.0. RESULTS: A total of twelve studies provided sufficient data for the quantitative analysis. For the diagnosis of chondrosarcoma, the pooled sensitivity, specificity, and DOR of 18F-FDG PET were 0.84 (95% confidence interval [CI] 0.46 to 0.97), 0.82 (95% CI 0.55 to 0.94), and 24.244 (95% CI 1.985 to 96.148), respectively while those of 18F-FDG PET/CT were 0.94 (95% CI 0.86 to 0.97), 0.89 (95% CI 0.82 to 0.93), and 112.999 (95% CI 41.341 to 308.866), respectively. The pooled WMD of SUVmax were - 0.89 (95% CI -1.67 to -0.10) between benign cartilaginous lesions and grade 1 (G1) chondrosarcoma, -1.94 (95% CI -2.76 to -1.12) between G1 and grade 2 (G2) chondrosarcoma, and - 2.37 (95% CI -5.79 to 1.05) between G2 and grade 3 (G3) chondrosarcoma. CONCLUSIONS: In a word, 18F-FDG PET/CT revealed excellent accuracy in the diagnosis of chondrosarcoma and might assist in clinical decision-making. Meanwhile, although SUVmax alone showed restricted ability to differentiate benign cartilaginous lesions and G1 chondrosarcoma, as well as between G2 and G3 chondrosarcoma, it can identify intermediate/high-grade chondrosarcoma from low-grade ones. LEVEL OF EVIDENCE: Level I evidence, a summary of meta-analysis.

The PI3K/AKT pathway promotes fracture healing through its crosstalk with Wnt/ß-catenin.

PI3K/AKT is one of the key pathways that regulate cell behaviors including apoptosis, proliferation, and differentiation. Although previous studies have demonstrated that this pathway is a crucial regulator of osteoblasts, the role of PI3K/AKT in fracture healing remains unclear. It is well known that the Wnt/ß-catenin pathway plays an essential role in bone regeneration. However, whether there exists crosstalk between Wnt/ß-catenin and PI3K/AKT in regulating osteoblasts and bone repair has not been reported. To address these issues, we establish a stabilized fracture model in mice and show that PI3K inhibitor LY294002 substantially inhibits the bone healing process, suggesting that PI3K/AKT promotes fracture repair. More importantly, we report that PI3K/AKT increases phosphorylation of GSK-3ß at Ser9 and phosphorylation of ß-catenin at Ser552 in fracture callus and murine osteoblastic MC3T3-E1 cells, both of which lead to ß-catenin stabilization, nuclear translocation, as well as ß-catenin-mediated TCF-dependent transcription, suggesting that ß-catenin is activated downstream of PI3K/AKT. Furthermore, we show that ICG001, the inhibitor of ß-catenin transcriptional activity, attenuates PI3K/AKT-induced osteoblast proliferation, differentiation, and mineralization, indicating that the PI3K/AKT/ß-catenin axis is functional in regulating osteoblasts. Notably, the PI3K/AKT pathway is also activated by Wnt3a and is involved in Wnt3a-induced osteoblast proliferation and differentiation. Hence, our results reveal the existence of a Wnt/PI3K/AKT/ß-catenin signaling nexus in osteoblasts, highlighting complex crosstalk between PI3K/AKT and Wnt/ß-catenin pathways that are critically implicated in fracture healing.

Targeting the SH3 domain of human osteoclast-stimulating factor with rationally designed peptoid inhibitors.

Human osteoclast-stimulating factor (hOSF) is an intracellular protein produced by osteoclasts that induces osteoclast formation and bone resorption. The protein contains a modular Src homology 3 (SH3) domain that mediates the intermolecular recognition and interaction of hOSF with its biological partners. Here, we proposed targeting the hOSF SH3 domain to disrupt hOSF-partner interactions for bone disease therapy by using SH3 inhibitors. In the procedure, the primary sequences of three known hOSF-interacting proteins (c-Src, SMN and Sam68) were parsed, from which totally 31 octapeptide segments that contain the core SH3-binding motif PXXP were extracted, and their binding behavior to hOSF SH3 domain was investigated at structural level using a biomolecular modeling protocol. Several SH3-binding candidates were identified theoretically and then determined to have high or moderate affinity for the domain using fluorescence spectroscopy assays. One potent peptide (425) APPARPVK(432) (Kd = 3.2 µM), which corresponds to the residues 425-432 of Sam68 protein, was used as template to derive N substitution of peptides (peptoids). Considering that proline is the only endogenous N-substituted amino acid that plays a critical role in SH3-peptide binding, the substitution was addressed at the two key proline residues (Pro427 and Pro430) of the template peptide with nine N-substituted amino acid types. By systematically evaluating the structural and energetic effects of different N-substituted amino acids presenting at the two proline sites on peptide binding, we rationally designed five peptoid inhibitors and then determined in vitro their binding affinity to hOSF SH3 domain. Consequently, two designed peptoids APPAR(N-Clp)VK and APPAR(N-Ffa)VK with Pro430 replaced by N-Clp and N-Ffa were confirmed to have increased (Kd = 0.87 µM) and comparable (Kd = 2.9 µM) affinities relative to the template, respectively. In addition, we also found that the Pro427 residue plays an essential role in restricting peptide/peptoid conformations to polyproline II (PPII) helix as the basic requirement of SH3 binding so that the residue cannot be modified. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Evaluation of Degenerative Lumbar Scoliosis After Short Segment Decompression and Fusion.

The objective of this study was to investigate short segment decompression of degenerative lumbar scoliosis (DLS) and the efficiency of fusion treatment.After DLS surgery, the patients were retrospectively reviewed using the VAS (visual analog scale) and ODI (Oswestry Disability Index) to assess clinical outcomes. All patients underwent posterior lumbar decompressive laminectomy, pedicle screw internal fixation, and posterolateral bone graft fusion surgery. Radiographic measurements included the scoliotic Cobb angle, the fused Cobb angle, the anterior intervertebral angle (AIA), the sagittal intervertebral angle (SIA), and lumbar lordosis angle. The relationships between these parameters were examined by bivariate Pearson analysis and linear regression analysis.Preoperatively, the Cobb angle at the scoliotic segment was 15.4°, which decreased to 10.2° immediately following surgery (P < 0.05). The AIA significantly increased by the last follow-up (4.4 ± 3.4) compared with pre- and postoperative values (2.5 ± 2.8 and 2.2 ± 2.4, respectively; P < 0.05). However, the scoliotic Cobb angle and the AIA did not correlate with the VAS or ODI scores. At the final follow-up, no patients had pseudoarthrosis or internal instrumentation-related complications.Short fusion surgical treatment results in limited DLS correction, with correction loss over time. The AIA between the upper adjacent segment and proximal fused vertebra continues to increase postoperatively, which does not exacerbate clinical symptoms, as reflected by the low reoperation rates for repairing degeneration at adjacent levels.

Comparative Study of Modified Posterior Operation to Treat Kümmell's Disease.

The present study aimed at examining the curative effect of modified posterior operation on treatment of Kümmell's disease. About 30 patients of Kümmell's disease with complete image and clinical data treated during June 2004 to July 2013 were conducted with anterior and posterior approaches, respectively. Kyphotic Cobb angle, fractured vertebra wedge angle, and the anterior and posterior heights of fractured vertebra were all measured through x-ray before and after operation, and the pain visual analog scale (VAS) was determined for evaluating the effect of operations. The injury and restoration of neurological function were assessed using Frankel classification. Patients in group A were treated with anterior operation, whereas group B was posterior operation. Postoperatively, VAS score, kyphotic Cobb angle, anterior vertebra height, and pathologic vertebra wedge angle were all significantly improved in patients with Kümmell's disease receiving modified posterior operation (group B). Similar results were also observed in patients with anterior operation. The improvement of VAS and correction rate of kyphotic Cobb angle indicated equivalent effects of posterior and anterior operations. Meanwhile, alleviated neurological function damage was observed in 2 groups. Relevant factor analysis illustrated that there was no significant correlation of the severity and improvement rate of pain symptoms with age, medical history, anterior and posterior vertebra heights, kyphotic Cobb angle, and pathological vertebra wedge angle. Compared with traditional anterior approach, modified posterior operation, adopting transpedicular vertebral body grafting combined with vertebral pedicle screw fixation, could produce equivalent effects on kyphosis correction, pain relief, and improvement of neurological function in patients with Kümmell's disease.

Comparison of rhBMP-2 versus Autogenous Iliac Crest Bone Graft for 2-Level Anterior Cervical Discectomy and Fusion for Cervical Spondylotic Myelopathy.

BACKGROUND: Few studies have examined the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) in 2-level anterior cervical discectomy and fusion (ACDF). The purpose of this study was to compare the outcomes in a series of patients with CSM treated with 2-level ACDF with or without rhBMP-2. MATERIAL AND METHODS: The retrospective study included a total of 146 patients with CSM. The rhBMP-2 group consisted of 73 patients who underwent 2-level ACDF with rhBMP-2. A total of 73 patients who also received 2-level ACDF with autogenous ICBG alone were included in the matched-pair ICBG group with a ratio of 1:1, based on age, sex, and BMI. All data, including fusion rate and time, VAS, JOA score, operative date, and complications, were assessed. RESULTS: With respect to the length of hospital stay, operative times, and blood loss, there were no significant difference between the 2 groups. However, the rhBMP-2 group presented a shorter fusion time (P<0.013) and higher fusion rate (P<0.036) than the ICBG group. In the rhBMP-2 group, 22% required additional treatment for complications compared to 18% of patients in the ICBG group, which showed no significant difference (P=0.543). CONCLUSIONS: The application of rhBMP-2 in 2-level ACDF showed higher fusion rates, shorter fusion time, and similar function outcomes compared to those who received ACDF with ICBG alone.

Down-regulation of microRNA152 is associated with the diagnosis and prognosis of patients with osteosarcoma.

Potential values of microRNA152 (miR-152) as a serum diagnostic and prognostic biomarker have not been determined in human osteosarcoma. By detecting the expression of miR-152 among 80 osteosarcoma patients, 20 periostitis patients and 20 healthy individuals using qRT-PCR, we aimed to explore the clinical significance of miR-152 in osteosarcoma patients. The expression of miR-152 was significantly decreased in patients with osteosarcoma compared to patients with periostitis (P<0.01) and healthy controls (P<0.01). The relationship between clinicopathologic characteristics and miR-152 was analyzed by chi-square test. The outcome indicated that miR-152 might be linked with the development of osteosarcoma. Moreover, the receiver operating characteristic (ROC) curve was performed to estimate the diagnostic value of miR-152. The result demonstrated that miR-152 might be a promising diagnostic marker of osteosarcoma with an AUC of 0.956, combing with 92.5% specificity and 96.2% sensitivity. The relationship between miR-152 and overall survival of osteosarcoma patients was analyzed by Kaplan-Meier curve and log rank test. As a result, the survival time of patients with low miR-152 expression was significantly shorter than those with high miR-152 expression (P<0.001). Then Cox regression analysis was used to estimate the prognostic value of miR-152 in osteosarcoma. The outcomes showed that low miR-152 expression (P=0.004) might be a potential independent prognostic marker for osteosarcoma patients. These findings suggested that down-regulation of miR-152 could be considered as a predictor for diagnosis and prognosis of osteosarcoma patients.

Association between CTLA-4 gene polymorphism and ankylosing spondylitis: a case-control study.

AIMS: The aim of our study was to evaluate the association between CTLA-4 polymorphisms (+49A/G, -318C/T and CT60A/G) and ankylosing spondylitis (AS) susceptibility. METHODS: A total of 120 AS cases and healthy controls, matched on the age and gender, were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) were used to determine the gentypes of +49A/G, -318C/T and CT60A/G polymorphisms. Genotype distribution in control group was assessed by Hardy Weinberg Equilibrium (HWE) test. Odds ratio (OR) with 95% confidence interval (95% CI) were adopted to evaluate the relationship of CTLA-4 polymorphisms and AS susceptibility. RESULTS: In our study, genotype distribution of the three polymorphisms in control group was consistent with the HWE (P > 0.05). The genotype analysis showed that AA genotype of + 49A/G polymorphism could increase the risk for AS (OR=2.357, 95% CI=1.127-4.930). Moreover, the frequency of A allele was also presented as a risk factor for AS. Additionally, AA genotype and A allele of CT60A/G appeared to be related with AS susceptibility (OR=2.610, 95% CI=1.047-6.510; OR=1.751, 95% CI=1.160-2.641). However, the T allele of -318C/T appeared to be a protective factor for AS (OR=0.383, 95% CI=0.228-0.643). CONCLUSION: In summary, there existed significant association between CTLA-4 gene polymorphisms and increased or decreased risk for AS.

TNF-α and IL10 polymorphisms interaction increases the risk of ankylosing spondylitis in Chinese Han population.

AIMS: The target of this article was to reveal the role of tumor necrosis factors α (TNF-α) and Interleukin-10 (IL10) gene polymorphisms in ankylosing spondylitis (AS) development and explore the interaction between these two gene polymorphisms. METHODS: The genotyping of gene polymorphims was conducted using ABI Taqman assay method in 84 AS patients and 92 healthy people. Hardy-Weinberg equilibrium (HWE) was checked in the control group and the genotypes and alleles difference were compared with χ(2) test. Odds ratio (OR) with 95% confidence interval (CI) was calculated to identify the strength of association between gene polymorphism and disease. Meanwhile, multifactor dimensionality reduction (MDR) method was used to analysis the interaction between gene polymorphisms. RESULTS: The genotypes CG+CC of the minor allele in IL10 rs1878672 in cases was obviously higher frequency than the controls (P=0.03) and the minor allele C was also associated with the increased risk of AS, compared with G allele (OR=2.05, 95% CI=1.08-3.89). Rs3024490 in IL10 also showed a significant correlation to the onset risk of AS (GG vs. TT: OR=3.03, 95% CI=1.04-8.87; G vs. T: OR=1.70, 95% CI=1.08-2.68). What's more, there was the interaction between TNF-α rs3093662 and IL10 rs3021094, rs3024490 polymorphisms in AS. CONCLUSIONS: IL10 rs1878672 and rs3024490 polymorphisms obviously increase the susceptibility to AS, but not TNF-α rs3093662. Both IL10 and TNF-α polymorphisms may affect the onset of AS.

Genetic analysis of TNFST15 variants in ankylosing spondylitis.

AIMS: The purpose of this study was to explore the role of TNF-like ligand 1A (TL1A) gene (TNFST15) polymorphisms (rs3810936, rs7848647, and rs6478109) in the generation of ankylosing spondylitis (AS). METHODS: Polymerase chain reaction (PCR) and sequencing were used to conduct the genotyping of TNFSF15 polymorphisms in 113 AS patients and 120 healthy persons as the case and control groups. The frequencies comparison was performed by chi-square or t test between the two groups. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated to represent the correlation between TNFSF15 polymorphism and AS. Besides, genotypes distribution of the former in controls was checked by Hardy-Weinberg equilibrium (HWE). RESULTS: There was statistically significant difference in AS patients and controls based on family history. Among TNFSF15 polymorphisms, only TT genotype frequency of rs3810936 in cases was obviously high, compared with the controls (P=0.04), the results indicated that TT was a high-risk genotype (OR=2.31, 95% CI=1.03-5.20). However, both of rs6478109, rs7848647 polymorphisms didn't show any association with AS. CONCLUSION: Rs3810936 of TNFSF15 were related to the risk of AS and we should pay more attention to the role of TNFSF15 polymorphisms in the pathogenesis of AS in the future.

Runx2 induces bone osteolysis by transcriptional suppression of TSSC1.

Advanced breast cancers frequently metastasize to bone, resulting in osteolytic lesions, however, the underlying mechanisms are poorly understood. Runx2, a bone-specific transcriptional factor, is abnormally expressed in highly metastatic breast cancer cells. Here, we found that TSSC1 inhibits breast cancer cell invasion. Subsequently, TSSC1 is confirmed as a target of Runx2 and is negatively regulated by Runx2. Furthermore, overexpression of Runx2 induces bone osteolysis in a TSSC1-dependent manner. Our results may provide a strategy for the treatment of breast cancer and the prevention of skeletal metastasis.