MiR-34a Enhances Chondrocyte Apoptosis, Senescence and Facilitates Development of Osteoarthritis by Targeting DLL1 and Regulating PI3K/AKT Pathway

Background/Aims: Osteoarthritis (OA) is the prevalent degenerative disease caused by various factors. MicroRNAs are important regulators in the inflammation and immune response. The aim of this study was to investigate the effect of microRNA-34a (MiR-34a) on the death of chondrocytes, senescence, as well as its role in OA progression. Methods: A series of experiments involving CCK-8, flow cytometry, β-galactosidase staining and wound healing assays were conducted to determine the cellular capabilities of proliferation, cell apoptosis, senescence and the ability of cells to recover from injury, respectively. Binding sites between miR-34a and delta-like protein 1 (DLL1) were identified using a luciferase reporter system, whereas mRNA and protein expression of target genes was determined by RT-PCR and immunoblot, respectively. OA model was generated via surgery. Results: We found that miR-34a expression was increased in the cartilage of OA patients. In rat chondrocytes and chondrosarcoma cells, miR-34a transfections noticeably inhibited the expression of DLL1, triggered cell death and senescence, suppressed proliferation, and prevented scratch assay wound closure. However, transfection of a miR-34a inhibitor displayed adverse effects. Additionally, secretion and expression of factors associated with cartilage degeneration were altered via miR-34a. Moreover, miR-34a directly inhibits DLL1 mRNA. Furthermore, concentrations of DLL1, total PI3K, and p-AKT declined in chondrocytes that overexpress miR-34a. DLL1 overexpression elevated PI3K and p-AKT levels, and eliminated cell death triggered by a miR-34a mimic. In vivo, miR-34a remarkably inhibited miR-34a up-regulation, while enhanced the level of DLL1 expression. In the knee joints of surgery-induced OA rats, articular chondrocyte death and loss of cartilage were attenuated via miR-34a antagomir injection. Conclusions: These findings indicate that miR-34a contributes to chondrocyte death, causing OA progression through DLL1 and modulation of the PI3K/AKT pathway

Analysis of sales strategy for the air conditioning industry - from the perspective of industry lifecycle

台灣位處於亞熱帶氣候，空調已成為家家戶戶必備使用的產品，而空調產品主要可以區分為三大市場，包含：家用市場、商用市場及大型中央空調市場。本研究主要從中央空調產業生命週期中探討該產業之領先者與追隨者在該市場上之銷售策略之分析，其探討議題如下： (一) 探討追隨者與領先者對該產業之生命週期看法 (二) 探討追隨者企業在該領域上如何與領先者競爭 本研究經由選擇台灣中央空調產業的兩家公司進行深度訪談，並就議題進行探討得到以下結論。領先者若無法有效的進行防禦以維持現有的市場占有率，其仍會受到其他競爭者的競爭而受影響，特別是當其他競爭者透過併購策略、上下游的垂直整合、產品線的水平整合等方式，讓本身內部資源與能力上的提升時，將會影響領先者在市場上地位。Taiwan is in a subtropical climate where air conditioning has become essential for every household product, and can be divided into three major markets, including: residential, commercial and central air conditioning market. This study focuses on the central air-conditioning industry life cycle in Taiwan to further explores the leaders and followers of the industry by the market sales strategy analysis. The discussion topics are as follows: (A) To explore the followers and leaders of the industry from life cycle’s perspective; (B) Explore how followers can compete with leaders in the industry. The study selected two companies in Taiwan's central air-conditioning industry to conduct in-depth interviews and discussed the issues to get the following conclusions. Leaders who are unable to effectively defend themselves to maintain their existing market share, will be affected by competition from other competitors, especially when other competitors go through the mergers and acquisitions, vertical integration of upstream and downstream, product line level integration and so on so that their own internal resources and ability to enhance, will affect the leader in the market position

Improve the Efficiency of Surgery for Femoral Shaft Fractures with A Novel Instrument: A Randomized Controlled Trial

<div><p>Objective</p><p>To improve the efficacy of closed reduction and wire guiding during intramedullary nail internal fixation in femoral shaft fractures.</p><p>Methods</p><p>A novel instrument was designed and manufactured. Sixty-eight patients were enrolled from February 2011 to December 2013. The instrument designed was used during the operation in the experimental group, but not in the control group.</p><p>Results</p><p>All patients exhibited fracture union, excluding 1 patient in the experimental group and 2 in the control group who had non-union; all of whom achieved fracture union with reoperation. There were no statistically significant differences in operative blood loss or duration of hospital stay between the groups (P > 0.05). The operative time, frequency of wire drilling, and number of open reduction cases, were significantly smaller in the experimental group than in the control group (P < 0.05).</p><p>Conclusion</p><p>Femoral shaft fractures are difficult to reduce using general methods; the novel instrument showed high clinical value and proved effective and safe in assisting with closed reduction and intramedullary nail fixation for femoral shaft fractures.</p><p>Trial Registration</p><p>ChiCTR <a href="http://www.chictr.org.cn/showprojen.aspx?proj=12335" target="_blank">ChiCTR-ICR-15007335</a></p></div

Radiographs showing application of the instrument in an operation for a femoral shaft fracture.

<p>(a, b) preoperative condition of the fracture (c, d) completed closed reduction with fracture reduction device (e, f) drilling into the proximal femoral medullary cavity using a Kirschner wire (1.5 mm) through the short sleeve (g, h) drilling into the distal femoral medullary cavity using a Kirschner wire.</p

Details of all patients, in both groups, with femoral shaft fracture.

<p>Details of all patients, in both groups, with femoral shaft fracture.</p

Comparison of the operative time, operative blood loss, frequency of drilling, number of open reduction cases, and hospitalization time between groups.

<p>Comparison of the operative time, operative blood loss, frequency of drilling, number of open reduction cases, and hospitalization time between groups.</p

Picture of the instrument developed.

<p>(a) bone forceps, bar, and connectors of the fracture reduction device; (b) column, calibrated bar, and slider of the guidewire-aiming device; (c, d) assembled fracture reduction device on a model of the femur; (e, f) assembled fracture reduction device and guidewire-aiming device on a model of the femur.</p