Effects of full-threaded headless cannulated compression screws and anatomical plates on the efficacy, safety, and prognosis of patients with triplane fractures of the distal tibia.

OBJECTIVE: To compare the clinical efficacy, safety, and prognosis of full-threaded headless cannulated compression screws (HCCSs) and anatomical plates (APs) in the treatment of triplane fractures of the distal tibia. METHODS: In this retrospective study, 74 patients with triplane fractures of the distal tibia treated in our hospital from April 2017 to March 2019 were selected as the research subjects. Among them, 38 patients receiving full-threaded HCCSs were assigned to the research group (RG), and the remaining 36 patients receiving APs were assigned to the control group (CG). The general indices, including operation, fracture healing, and ambulation times, efficacy, and complications were recorded and compared between the two groups. Visual analogue scale (VAS) was applied to assess pain, and a quality of life (QOL) survey was conducted at 6 months after surgery. RESULTS: Compared with the CG, the operation time, fracture healing time, and ambulation time of the RG were significantly shortened (P<0.05). The proportion of patients with excellent and good outcomes and Mazur Scores in the RG were higher than those in the CG (P<0.05). The frequency of complications in the RG was lower than that in the CG (P<0.05). The preoperative VAS score did not exhibit significant differences between the two groups (P<0.05), but the scores in the RG at T1 and T2 were significantly lower than those in the CG (P<0.001). The QOL score in the RG (76.17±8.57) was also significantly higher than in the CG (71.54±8.02) (P<0.05). CONCLUSION: Full-threaded HCCSs are more effective and safer than APs and can effectively improve the prognosis of patients with triplane fractures of the distal tibia.

Expression and anti-inflammatory role of activin receptor-interacting protein 2 in lipopolysaccharide-activated macrophages.

The bacterial endotoxin lipopolysaccharide (LPS), a key pathogenic stimulator, can induce the activation of macrophages. Activin receptor-interacting protein 2 (ARIP2), an intracellular signaling protein, has a wide histological distribution, however, whether ARIP2 is involved in regulation of activation of macrophages was not well characterized. Here, by immunocytochemical staining, we found that ARIP2 protein existed in monocyte-macrophage cell line RAW264.7 cells and peritoneal macrophages of mouse, and ARIP2 expression in RAW264.7 cells was up-regulated by LPS. Furthermore, the results revealed that ARIP2 overexpression in the LPS-activated RAW264.7 cells inhibited the productions of IL-1ß and TNFα, phagocytic activities and CD14 expression, whereas did not alter expressions of MyD88, TLR2 and TLR4. Additionally, in vivo ARIP2 overexpression also reduced the productions of IL-1ß and TNFα from the LPS-stimulated peritoneal macrophages of mouse. These data suggest that ARIP2 may play an anti-inflammatory role in macrophages via inhibiting CD14 expression.

The effects of activin A on the migration of human breast cancer cells and neutrophils and their migratory interaction.

Activin A belongs to the superfamily of transforming growth factor beta (TGFß) and is a critical regulatory cytokine in breast cancer and inflammation. However, the role of activin A in migration of breast cancer cells and immune cells was not well characterized. Here, a microfluidic device was used to examine the effect of activin A on the migration of human breast cancer cell line MDA-MB-231 cells and human blood neutrophils as well as their migratory interaction. We found that activin A promoted the basal migration but impaired epidermal growth factor (EGF)-induced migration of breast cancer cells. By contrast, activin A reduced neutrophil chemotaxis and transendothelial migration to N-Formyl-Met-Leu-Phe (fMLP). Finally, activin A promoted neutrophil chemotaxis to the supernatant from breast cancer cell culture. Collectively, our study revealed the different roles of activin A in regulating the migration of breast cancer cells and neutrophils and their migratory interaction. These findings suggested the potential of activin A as a therapeutic target for inflammation and breast cancers.

Molecular modeling and biological effects of peptidomimetic inhibitors of TACE activity.

We investigated the molecular basis of specificity for the interaction between tumor necrosis factor-alpha converting enzyme (TACE) and peptidomimetic inhibitors. Four novel peptidomimetic TACE inhibitors (8a-d) were designed and synthesized by introducing a substituted sulfur group and a hydrophobic group to a novel matrix metalloprotease (MMP) inhibitor. Inhibition was determined by in vitro lipopolysaccharide (LPS) cytotoxicity tests in HL-60 cell lines and by measuring the expression of mTNF-alpha using FCM techniques and immunohistochemistry in vivo. We simulated the interaction of the inhibitors with the 3D structure of the TACE active site in the Brookhaven Protein Database (PDB). The four inhibitors (8a-d) inhibited activity by 9.1%, 54.5%, 27.3%, and 54.5%, respectively. 8b and 8d showed significant in vitro inhibition in cytotoxicity tests, which corresponded to the molecular docking results. 8d also showed inhibitory activity in vivo. We explored the interface between enzyme and substrate by combining bioinformatics with experimental observations to further the development of specific TACE inhibitors to reduce inflammatory responses.

Comparison of properties of tumor necrosis factor-alpha converting enzyme (TACE) and some matrix metalloproteases (MMPs) in catalytic domains.

The crystal structural data of TACE, MMP-1, MMP-2, MMP-3 and MMP-9 were obtained from PDB database, and then their catalytic domains' properties including conformation, molecular surface hydrophobicity and electrostatic potential were analyzed and compared by using Insight II molecular modeling software. It was found that the conformation and molecular surface hydrophobicity of catalytic domains of TACE and MMPs were not obviously different, but the molecular surface electrostatic potential of catalytic domain of TACE and MMPs had obvious differences. The findings are helpful in the Rational Drug Design of TACE selective inhibitor.