Meta-Analysis of the Association of HLA-DRB1 with Anti-Citrullinated Protein Antibody-Positive and Anti-Citrullinated Protein Antibody-Negative Rheumatoid Arthritis

Because of genetic complex and variations of auto antibodies of rheumatoid arthritis (RA) in different populations, the data on the association of HLA-DRB1 alleles in anti-citrullinated protein antibody of (ACPA) RA were inconsistent. The purpose of the study is to systematically summarize results of published data through performing a meta-analysis using data in which HLA-DRB1 alleles are associated with ACPApositive RA and ACPA-negative RA. In this study, we collected data from 12 studies with 13,861 cases and 12,896 controls. Information in these studies included HLADRB1 typing and ACPA status from different countries. Odds ratios (ORs) and corresponding 95% confidence intervals (CI) were used to analyze the association of different HLA-DRB1 alleles with ACPA-positive RA or ACPA-negative RA. To correct skewing data, the analysis of ACPA-status was stratified by patient distribution. Our analyses indicate that in ACPA-positive RA, all patients with RA had significantly higher frequencies of HLA-DRB1*01, *04, *0401, *0405, *07, *11, *13 and *14 than controls. One of the HLA-DRB1*07, *11, *13 and *14 showed protective association with RA. In addition, HLA-DRB1*03, *10 and *12 had more influence than control to RA in European populations;the HLA-DRB1*03 and *12 alleles were associated with the protection. In ACPA-negative RA, only DRB1*07 was associated with the protection (OR 0.53 [95% CI 0.36 - 0.76]) among all HLA-DRB1 alleles in European populations. In ACPA-positive RA, currently available results indicate that *01, *04, *0401 and *0405 are susceptible, while HLA-DRB1*07, *11, *13 and *14 are protective in all populations. While the HLA-DRB1*10 is susceptible, HLA-DRB1*03 and *12 show protective association with RA in European populations. Additionally, regardless of the positive or negative ACPA, the DRB1*07 is always associated with protection in European populations.

Leptin promotes proliferation and invasion of osteosarcoma cells by upregulating the expression of SIRT1

Osteosarcoma(OS)is a primary high-grade malignant bone neoplasm,and the prognosis ofOS remains poor due to early metastasis.Leptin plays an essential role in tumorigenesis,but the role of leptin in the development of OS is still not fully understood.In this study,we used a human osteosarcomaMG-63 cell line as an experimentalmodel.MG-63 cells were treated with leptin,and cell proliferation,apoptosis,adhesion,invasion,and gene expression,were evaluated.The results showed that leptin promoted proliferation,decreased adhesion,suppressed apoptosis,and promoted invasion,of MG-63 cells.Moreover,the expression of SIRT1 was upregulated in MG-63 cells exposed to leptin.Furthermore,MMP-2,8,and 9 were significantly upregulated by SIRT1,while SIRT1 knockdown inhibited the proliferation and invasion of MG-63 cells.In conclusion,our results suggest that leptin promotes OS cell proliferation and invasion by inducing the expression of SIRT1.

Efficiency and Advantages of Percutaneous Femoroplasty versus Proximal Femoral Replacement for Proximal Femur Metastases

Background: The proximal femur is the most common site of bone metastasis, and metastasis at this site can cause chronic, intolerable pain and even result in pathologic fractures, thereby negatively affecting patients’ quality of life. Selecting an appropriate method for resecting metastasis within the proximal femur requires thorough consideration of various factors, including the biological behavior of the primary tumor, the extent of the femur lesion, the current general systemic condition of the patient, and perioperative risks. Objective: To compare the perioperative safety of and early functional recovery following percutaneous femoroplasty (PFP) and proximal femoral replacement (PFR) in treating patients with metastasis of the proximal femur. Methods: We retrospectively analyzed the cases of 53 patients with proximal femur metastases who received surgical treatment by either PFP (n = 28) or PFR (n = 25). Perioperative blood loss, surgical time, and perioperative complications were compared between groups. Pain intensity according to the visual analogue scale (VAS) and early postoperative function according to the Karnofsky Performance Scale (KPS) were evaluated at 3, 7, and 30 days as well as 6 months after surgical treatment. Results: In the PFP group, the VAS scores were lower soon after operation than preoperation (P 0.05). PFP significantly and immediately improved patients’ quality of life as measured by the KPS in the early period after surgery (preoperative vs 3 days postoperative, P < 0.01), but the patients who underwent PFR suffered a short-term decrease in quality of life (preoperative vs 3 days postoperative, P < 0.01). Blood loss (P < 0.01) and operating time (P < 0.01) were significantly less than PFP. The complication rate was higher in the PFR group (28%) than in the PFP group (3.6%). The results also showed no difference in survival time between the two groups. Conclusion: PFP is an attractive minimally invasive therapeutic option for proximal femur metastasis that can significantly improve the patient’s quality of life in the short term.

Tumor-associated macrophages in osteosarcoma

Osteosarcoma(OS)is the most common primary bone tumor in children and adolescents.It is an aggressive tumor with a tendency to spread to the lung,which is the most common site of metastasis.Patients with advanced OS with metastases have poor prognoses despite the application of chemotherapy,thus highlighting the need for novel therapeutic targets.The tumor microenvironment(TME)of OS is confirmed to be essential for and supportive of tumor growth and dissemination.The immune component of the OS microenvironment is mainly composed of tumor-associated macrophages(TAMs).In OS,TAMs promote tumor growth and angiogenesis and upregulate the cancer stem cell-like phenotype.However,TAMs inhibit the metastasis of OS.Therefore,much attention has been paid to investigating the mechanism of TAMs in OS development and the progression of immunotherapy for OS.In this article,we aim to summarize the roles of TAMs in OS and the major findings on the application of TAMs in OS treatment.