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Despite growing evidence that Long noncoding RNAs (lncRNAs) can regulate gene expression and widely take part in autoimmune and inflammatory diseases, our knowledge of systemic lupus erythematosus (SLE)-related lincRNAs remains limited. In this study, we aimed to explore the contribution of the lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) to the pathogenesis of SLE. PBMCs were obtained from SLE patients and healthy donors. The expression levels of MALAT-1 were measured by quantitative PCR. Small interfering RNA (siRNA) was then used to knock down the expression of MALAT1 in order to determine the role of MALAT1 in the expression levels of IL-21 and SIRT1 signaling pathway in primary monocytes of SLE patients. Here, we found MALAT-1 expression was abnormally increased in SLE patients and predominantly expressed in human monocytes. Additionally, silencing MALAT-1 significantly reduced the expression of IL-21 in primary monocytes of SLE patients. Furthermore, MALAT-1 exerts its detrimental effects by regulating SIRT1 signaling. Our results demonstrate that MALAT-1 is the key regulatory factor in the pathogenesis of SLE and provides potentially novel target for therapeutic intervention.

Purpose:This study examined the mechanisms of osteoclast-mediated bone invasion in a model of oral squamous cell carcinoma (OSCC). C3H/HeN mice were inoculated with SCC VII cells into the masseter region to establish an animal model of mandibular invasion by OSCC. Experimental Design:The mice were divided into three groups: a control group, given daily s.c. injections of saline; group 1, given 2 Ag per mouse per day of the bisphosphonate YM529; and group 2, given 10 Ag per mouse per day of YM529. After 3 weeks of treatment, the lesions were studied by micro-computed tomography. After tartrate-resistant acid phosphatase (TRAP) staining, the osteoclasts were easily identified, and the percentages of the area occupied by osteoclasts were calculated by computer for each sample. The tumors were analyzed by RT-PCR to determine the mRNA expression of interleukin-6 (IL-6), parathyroid hormone^related protein (PTHrP), tumor necrosis factor-a (TNF-a), receptor activator of nuclear factor-nB (RANK), RANK ligand (RANKL), and osteoprotegerin. Results: SCC VII cells rapidly multiplied in the masseter muscle of the mice. Bone invasion was evident only in the control group on micro-computed tomography. On TRAP-stained slices, the percentages of osteoclasts in groups 1 and 2 were significantly lower than that in the control group. The mRNA expressions of IL-6, PTHrP,THF-a, and RANK decreased as the concentration of YM529 increased. Conclusions: We conclude that various cancer-derived cytokines play important roles in the invasion of bone by OSCC. YM529, a third-generation bisphosphonate, can suppress osteoclastmediated bone invasion by OSCC. The mechanism of this effect might involve inhibition of cytokines such as IL-6, PTHrP,TNF-a, and RANK byYM529.

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Background Deep vein thrombosis (DVT) is one of the life-threatening complications of total joint arthroplasty (TJA) postoperatively, and its risk factors are still controversial. The aim of this study was to identify the risk factors of DVT after TJA. Study design and methods A nested case-control study based on a large dataset of 15,326 patients undergoing TJA was performed. Potential risk factors of DVT and demographic information were extracted from the electronic health record. Patients with DVT (73 patients) were treated as study group while non-DVT patients who were matched 1:4 according to the anticoagulant type, were considered as control group (292 patients). These variables of potential risk factors for DVT including age, sex, body mass index (BMI), American Society of Anesthesiologists class, comorbidity, preoperative hemoglobin (HB) level and analgesic use, surgical site (knee or hip) and type, the start time of drug anticoagulation, ambulation time, transfusion, and whether to use tranexamic acid (TXA), drain, human serum albumin, and measures of physical thromboprophylaxis after operation were collected and evaluated by survival analysis and presented as P value and odds ratio with 95% confidence interval. Results There were 15,326 patients underwent TJA and 73 (0.48%) patients had DVT among them, and the occurrence rates were 0.71% for the patients underwent total knee arthroplasty (TKA) while 0.24% for total hip arthroplasty. The risk factors associated with DVT included TKA (compared with THA), advanced age (> 70 years), drain use, and delayed ambulation (≥ 72 h) postoperatively. Conclusion The present results suggest that the occurrence rate of DVT on the patients underwent TJA was low (0.48%) relatively. And the risk factors associated with increased risk of DVT included TKA (compared with THA), advanced age, drain use, and delayed ambulation postoperatively. Individualized and more efficient risk stratification protocols of anticoagulation after TJA for Chinese may need to be developed in the future.