Elbow Dislocation with Irretrievable Rotating-Rope Injury of the Forearm: Case Report and Literature Review.

BACKGROUND: Simultaneous dislocation of the elbow, radioulnar joint and proximal radius fracture with rotary noose injury to the medial ulna tubercle is extremely rare. An emergency surgery was performed to reduce it. The radial head with the backbone was reset after two hammers were fixed, then the radial capitulum safety was fixed with a locking plate. After the ulnar instability was examined, two Kirschner wires were drilled percutaneously to fix the elbow flexion at 100° under closed reduction, and two Kirschner wires were drilled percutaneously to fix the ulnar joint. Good follow-up results were achieved. To the best of our knowledge, this is the first report on this particular type of injury and on this approach to treating this type of injury. CASE PRESENTATION: We report the case of a 36-year-old male, who extended and landed on his left hand to protect his child in right arm before felling, resulting in severe pain and deformity of his left elbow and wrist and loss of movement in these joints. X-ray examination found proximal distal radioulnar joints, a proximal radial fracture and a dislocation bowstring in the ulna nodule. For a timely diagnosis in an emergency open reduction situation, accurate judgment of this injury is highly important. After 12 months of postoperative follow-up, the patient was symptom-free, and radiographs showed fracture healing. CONCLUSION: We performed emergency reduction and internal fixation of the elbow and successfully saved elbow function, no stability decrease and movement restriction. This case also provides a new reference for the treatment of this type of elbow fracture dislocation.

Rapamycin recruits SIRT2 for FKBP12 deacetylation during mTOR activity modulation in innate immunity.

The mammalian target of rapamycin (mTOR) is a serine-threonine kinase involved in cellular innate immunity, metabolism, and senescence. FK506-binding protein 12 (FKBP12) inhibits mTOR kinase activity via direct association. The FKBP12-mTOR association can be strengthened by the immunosuppressant rapamycin, but the underlying mechanism remains elusive. We show here that the FKBP12-mTOR association is tightly regulated by an acetylation-deacetylation cycle. FKBP12 is acetylated on the lysine cluster (K45/K48/K53) by CREB-binding protein (CBP) in mammalian cells in response to nutrient treatment. Acetyl-FKBP12 associates with CBP acetylated Rheb. Rapamycin recruits SIRT2 with a high affinity for FKBP12 association and deacetylation. SIRT2-deacetylated FKBP12 then switches its association from Rheb to mTOR. Nutrient-activated mTOR phosphorylates IRF3S386 for the antiviral response. In contrast, rapamycin strengthening FKBP12-mTOR association blocks mTOR antiviral activity by recruiting SIRT2 to deacetylate FKBP12. Hence, on/off mTOR activity in response to environmental nutrients relies on FKBP12 acetylation and deacetylation status in mammalian cells.

Elevated levels of interleukin-1ß, interleukin-6, tumor necrosis factor-α and vascular endothelial growth factor in patients with knee articular cartilage injury.

BACKGROUND: Inflammatory cytokines play a vital role in the occurrence of osteoarticular injury and inflammation. Whether inflammation-associated factors interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) are involved in the pathogenesis of keen articular cartilage injury remains poorly understood. AIM: To measure the levels of inflammatory factors [IL-1ß, IL-6, TNF-α and VEGF] in patients with knee articular cartilage injury. METHODS: Fifty-five patients with knee articular cartilage injury were selected as patient groups, who were divided into three grades [mild (n = 20), moderate (n = 19) and severe (n = 16)] according to disease severity and X-ray examinations. Meanwhile, 30 healthy individuals who underwent physical examination were selected as the control group. The levels of IL-1ß, IL-6, TNF-α and VEGF were measured by ELISA and immunohistochemical staining. RESULTS: Compared with the control group, patient groups displayed significantly higher levels of IL-1ß, IL-6, TNF-α and VEGF, and the extent of increase was directly proportional to the severity of injury (P < 0.05). In addition, the number of cells with positive staining of IL-1ß, IL-6, TNF-α and VEGF in the synovial membrane were significantly increased, along with increased disease severity (P < 0.05). After treatment, the scores of visual analogue scale and the Western Ontario and McMaster University of Orthopaedic Index in patient groups were 2.26 ± 1.13 and 15.56 ± 7.12 points, respectively, which were significantly lower than those before treatment (6.98 ± 1.32 and 49.48 ± 8.96). Correlation analysis suggested that IL-1ß and TNF-α were positively correlated with VEGF. CONCLUSION: IL-1ß, IL-6, TNF-α and VEGF levels are increased in patients with knee articular cartilage injury, and are associated with the disease severity, indicating they might play an important role in the occurrence and development of knee articular cartilage injury. Furthermore, therapeutically targeting them might be a novel approach for the treatment of keen articular cartilage injury.

Functional Role of Histidine in the Conserved His-x-Asp Motif in the Catalytic Core of Protein Kinases.

The His-x-Asp (HxD) motif is one of the most conserved structural components of the catalytic core of protein kinases; however, the functional role of the conserved histidine is unclear. Here we report that replacement of the HxD-histidine with Arginine or Phenylalanine in Aurora A abolishes both the catalytic activity and auto-phosphorylation, whereas the Histidine-to-tyrosine impairs the catalytic activity without affecting its auto-phosphorylation. Comparisons of the crystal structures of wild-type (WT) and mutant Aurora A demonstrate that the impairment of the kinase activity is accounted for by (1) disruption of the regulatory spine in the His-to-Arg mutant, and (2) change in the geometry of backbones of the Asp-Phe-Gly (DFG) motif and the DFG-1 residue in the His-to-Tyr mutant. In addition, bioinformatics analyses show that the HxD-histidine is a mutational hotspot in tumor tissues. Moreover, the H174R mutation of the HxD-histidine, in the tumor suppressor LKB1 abrogates the inhibition of anchorage-independent growth of A549 cells by WT LKB1. Based on these data, we propose that the HxD-histidine is involved in a conserved inflexible organization of the catalytic core that is required for the kinase activity. Mutation of the HxD-histidine may also be involved in the pathogenesis of some diseases including cancer.