Potential Role of Bmal1 in Lipopolysaccharide-Induced Depression-Like Behavior and its Associated "Inflammatory Storm".

Inflammation plays an important role in the pathogenesis of depression; however, the underlying mechanisms remain unclear. Apart from the disordered circadian rhythm in animal models and patients with depression, dysfunction of clock genes has been reported to be involved with the progress of inflammation. This study aimed to investigate the role of circadian clock genes, especially brain and muscle ARNT-like 1 (Bmal1), in the linkage between inflammation and depression. Lipopolysaccharide (LPS)-challenged rats and BV2 cells were used in the present study. Four intraperitoneal LPS injections of 0.5 mg/kg were administered once every other day to the rats, and BV2 cells were challenged with LPS for 24 h at the working concentration of 1 mg/L, with or without the suppression of Bmal1 via small interfering RNA. The results showed that LPS could successfully induce depression-like behaviors and an "inflammatory storm" in rats, as indicated by the increased immobility time in the forced swimming test and the decreased saccharin preference index in the saccharin preference test, together with hyperactivity of the hypothalamic-pituitary-adrenal axis, hyperactivation of astrocyte and microglia, and increased peripheral and central abundance of tumor necrosis factor-α, interleukin 6, and C-reactive protein. Moreover, the protein expression levels of brain-derived neurotrophic factor, triggering receptor expressed on myeloid cells 1, Copine6, and Synaptotagmin1 (Syt-1) decreased in the hippocampus and hypothalamus, whereas the expression of triggering receptor expressed on myeloid cells 2 increased. Interestingly, the fluctuation of temperature and serum concentration of melatonin and corticosterone was significantly different between the groups. Furthermore, protein expression levels of the circadian locomotor output cycles kaput, cryptochrome 2, and period 2 was significantly reduced in the hippocampus of LPS-challenged rats, whereas Bmal1 expression was significantly increased in the hippocampus but decreased in the hypothalamus, where it was co-located with neurons, microglia, and astrocytes. Consistently, apart from the reduced cell viability and increased phagocytic ability, LPS-challenged BV2 cells presented a similar trend with the changed protein expression in the hippocampus of the LPS model rats. However, the pathological changes in BV2 cells induced by LPS were reversed after the suppression of Bmal1. These results indicated that LPS could induce depression-like pathological changes, and the underlying mechanism might be partly associated with the imbalanced expression of Bmal1 and its regulated dysfunction of the circadian rhythm.

Modified classification and single-stage microsurgical repair of posttraumatic infected massive bone defects in lower extremities.

Posttraumatic infected massive bone defects in lower extremities are difficult to repair because they frequently exhibit massive bone and/or soft tissue defects, serious bone infection, and excessive scar proliferation. This study aimed to determine whether these defects could be classified and repaired at a single stage. A total of 51 cases of posttraumatic infected massive bone defect in lower extremity were included in this study. They were classified into four types on the basis of the conditions of the bone defects, soft tissue defects, and injured limb length, including Type A (without soft tissue defects), Type B (with soft tissue defects of 10 × 20 cm or less), Type C (with soft tissue defects of 10 × 20 cm or more), and Type D (with the limb shortening of 3 cm or more). Four types of single-stage microsurgical repair protocols were planned accordingly and implemented respectively. These protocols included the following: Protocol A, where vascularized fibular graft was implemented for Type A; Protocol B, where vascularized fibular osteoseptocutaneous graft was implemented for Type B; Protocol C, where vascularized fibular graft and anterior lateral thigh flap were used for Type C; and Protocol D, where limb lengthening and Protocols A, B, or C were used for Type D. There were 12, 33, 4, and 2 cases of Types A, B, C, and D, respectively, according to this classification. During the surgery, three cases of planned Protocol B had to be shifted into Protocol C; however, all microsurgical repairs were completed. With reference to Johner-Wruhs evaluation method, the total percentage of excellent and good results was 82.35% after 6 to 41 months of follow-up. It was concluded that posttraumatic massive bone defects could be accurately classified into four types on the basis of the conditions of bone defects, soft tissue coverage, and injured limb length, and successfully repaired with the single-stage repair protocols after thorough debridement.

Effects of gene­activated matrix on autograft healing of anterior cruciate ligament.

The aim of the present study was to observe the effects of gene­activated matrix (GAM) on autograft healing of the anterior cruciate ligament. Forty­eight rabbits were randomly divided into groups A and B. Rabbits were used to construct models of anterior cruciate ligament reconstruction. In group A, transforming growth factor (TGF)­ß1 was locally injected into the bone tunnel, while in group B, empty vector was administered. Tendons were removed to observe histology and ultrastructure and to evaluate biomechanics at postoperative months 1, 3 and 6. Optical microscopy revealed increased numbers of fibroblasts and collagen fibers in group A at each time­point compared with B. Electron microscopy identified increased mitosis and abundance of fibroblasts, endoplasmic reticulum and mitochondria in group A at each time­point compared with B. No significant difference was identified in the biomechanical parameters between the 2 groups at postoperative month 1. At postoperative months 3 and 6, maximum force and elastic modulus were greater in group A compared with group B (P<0.0.5). No significant differences in other biochemical parameters were observed at these time­points. The healing ligament graft transfected with TGF­ß1 by GAM was observed to have improved tissue structure and biomechanical characteristics. The results of the current study may provide a theoretical basis for GAM application in ligament repair.

[Treatment of displaced humeral supracondylar fractures in children with external fixation using plaster or splint].

OBJECTIVE: To investigate the therapeutic effects of closed reduction and external fixation (plaster or splint) for the treatment of displaced humeral supracondylar fractures in children. METHODS: From March 2007 to September 2009,33 children (15 female and 18 male) with humeral supracondylar fractures treated in our hospital, ranging from 3 to 12 years old with an average of 6.4 years old. All the fractures were extension-type injuries, the flexion injures were excluded in our study. The humeral supracondylar fractures were classified according to Gartland classification. There were 21 Type H and 12 type III. In the initial treatment, all the patients were treated with closed reduction and external immobilization. The blood supply of the damaged upper extremity was evaluated before and after treatment. Clinical assessment was obtained at final follow-up using Flynn criteria, and radiologic assessment was obtained using Baumann and lateral humerocapitellar angles. RESULTS: All the children were treated successfully with closed reduction in the initial time; 24 children maintained limb alignment by external immobilization. Nine patients lost position due to the swelling around the elbow which affected unstable external fixation during the follow-up, 5 of which were treated with a repeated closed reduction and internal fixation with Kirschner wires, 4 of which were treated with traction. Thirty-one patients had a satisfactory outcome and 2 patients had an unsatisfactory outcome according to the Flynn criteria at the latest follows-up. CONCLUSION: Closed reduction and external stabilization is an important method for the treatment of displaced humeral supracondylar fractures in children. Making regular follow-up visits after closed reduction and casting is important for patients to maintain acceptable alignment, avoid complications and diagnose any loss of reduction.

The applications of arthroscopy on malleolus fractures.

It was well known that in 1918 Takagi performed the first arthroscopic inspection of a cadaver's knee in Japan.(1) His interest in this area laid the foundation for arthroscopy and facilitated the development of arthroscope. In 1931, Burman reported an experimental study on the arthroscopic exploration of cadaveric joints, but he believed that the ankle joint was unsuitable for such techniques because it was too narrow to pass through the posterior puncture.(2) Unexpectedly, several years later Takagi described a routine method for arthroscopic examination of the ankle.(1) Since 1970's, ankle arthroscopy had made some significant progress after almost four decades of silence. In 1972, Watanabe reported 28 cases adopting his newly-developed fiberoptic arthroscope and described the anteromedial, anterolateral and posterior approaches.(3) Then, in 1976, Chen reviewed his experience with ankle arthroscopy on 67 patients and 17 cadavers. He elaborately analyzed the various compartments within the ankle and described their anatomy in detail.(4) Subsequently, many authors reported their experiences and techniques in this field.(5-9) In 2000, Hintermann addressed his experience of the arthroscopic application in acute fractures of the ankle.(10) Meanwhile, with rich knowledge about the anatomic portals, some advanced technologies, including video camera, fiberoptic light transmission, joint distraction by invasive or non-invasive means and instruments for small joints, make it possible to perform diagnostic and operative arthroscopy in the ankle.