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Objectives: The transtibial pull‐out repair (TP) is a relatively new method for treating meniscal root tear; however, the clinical evaluation of its healing effect remains controversial. Due to ethical constraints and limitations of imaging techniques in humans, here we dynamically observe the healing effects of TP and TP with platelet‐rich plasma gel (PRG) at the histological level using an animal model. Methods: Platelet‐rich plasma (PRP) and PRG of rabbits were prepared. Platelet‐derived growth factor (PDGF) and transforming growth factor‐β1 (TGF‐β1) levels in PRP and PRG were determined using an enzyme‐linked immunosorbent assay. A rabbit model of anterior horn tear of the medial meniscus and TP surgery were created. PRG was injected between the anterior horn of the medial meniscus and the tibial tunnel. Rabbits were divided into three groups: the anterior horn tear group (Tear group), the anterior horn tear + TP group (TP group), and the anterior horn tear + TP + PRG group (TP + PRG group). The healing effect was observed dynamically using histopathological studies and biomechanical experiments. Results: The platelet content in PRP significantly increased to approximately 4.57 times that of whole blood. PDGF and TGF‐β1 concentrations in PRG increased to 2.46 and 4.15 times those in PRP, respectively. Hematoxylin and eosin (H&E) and Masson staining showed that the number of inflammatory cells in healing tissue decreased and the collagen fibers significantly increased in TP and TP + PRG groups at 4, 8, and 12 weeks postoperatively compared to those in Tear group. Neatly arranged, interlaced, and dense collagen fibers were found between the anterior horn and bone at 12 weeks. H&E and toluidine blue staining showed that the injury to the femoral condyle cartilage was alleviated. The healing performance in TP + PRG group was better and faster than that in TP group. The maximum tensile fracture strength of the meniscus progressively increased at 8 and 12 weeks postoperatively. Conclusions: Anterior horn injury of the medial meniscus in rabbits can be repaired using the TP technique, and the addition of autologous PRG to the bone tunnel promotes early healing of the meniscus and bone postoperatively. Meanwhile, both treatments can reduce the secondary damage to the cartilage due to osteoarthritis. [ABSTRACT FROM AUTHOR]

1. Rhein, an active ingredient in the root of rhubarb, is used for its beneficial effects in a variety of clinical applications including the treatment of osteoarthritis and diabetic nephropathy. However, its hepatotoxicity has been reported in recent years. Rhein belongs to the conjugate structure which could be activated to reactive metabolites (RMs) inducing side-effects. This study is to explore the relationship between RMs and hepatotoxicity. 2. Based on the early detection of RMs, we have established a series of key technologies to research rhein hepatotoxicity mechanism: IC50 shift experiments and reduced glutathione (GSH) trapping experiment are adopted to identify RMs. The model of low activity of CYP450 enzymes (CYPs) in primary rat hepatocyte is constructed to analyze the relationship between the primary metabolic enzyme and hepatotoxicity of rhein better. 3. The IC50 shift value for CYP2C19 is 1.989, it suggests that CYP2C19 could activate rhein to RM. The structure of RM is epoxide intermediate. Besides, it is found that CYP2C19 is a primary metabolic enzyme for rhein. In the cytotoxicity assay, it is reported that rhein could cause mitochondrial dysfunction. Furthermore, mitochondrial membrane potential (Δ ψm) and AST levels could be restored by adding inhibitor of CYP2C19 together with rhein, which further shows that CYP2C19 could mediate the hepatotoxicity of rhein. 4. We put forward the possible mechanism that reactive metabolite activation by CYP2C19 mediated rhein hepatotoxicity, it provides important information on predicting in vivo drug-induced liver injury (DILI). [ABSTRACT FROM AUTHOR]

For the first time, it has been demonstrated that a protein product can be oxidized readily by certain sanitizing agents through vapor transfer not only in a closed system but also in an open environment. The effect of several sanitizing agents on the oxidation of a model protein, IL-2 mutein, was investigated under different processing conditions. Reversed phase-high performance liquid chromatography (RP-HPLC) was used to separate and quantitate both intact and oxidized IL-2 mutein. It was found that peracetic acid or NaOCl oxidizes IL-2 mutein instantaneously, while H2O2-induced oxidation of IL-2 mutein is much slower in solution. The amount of protein oxidation product is proportional to the duration of sample exposure and the type and concentration of the sanitizing agent. In addition, sanitizing agents can accelerate protein oxidation during lyophilization, and the residual amount can promote oxidation of the lyophilized product during storage. These results strongly suggest that the sanitization process needs to be properly controlled and closely monitored during manufacturing of drug products that are sensitive to oxidation.