Identification of the CCL2 PI3K/Akt axis involved in autophagy and apoptosis after spinal cord injury.

Spinal cord injury (SCI) is a devastating neurological disease with no cure that usually results in irreversible loss of sensory and voluntary motor functions below the injury site. We conducted an in-depth bioinformatics analysis combining the gene expression omnibus spinal cord injury database and the autophagy database and found that the expression of the autophagy gene CCL2 was significantly upregulated and the PI3K/Akt/mTOR signaling pathway was activated after SCI. The results of the bioinformatics analysis were verified by constructing animal and cellular models of SCI. We then used small interfering RNA to inhibit the expression of CCL2 and PI3K to inhibit and activate the PI3K/Akt/mTOR signaling pathway; western blot, immunofluorescence, monodansylcadaverine, and cell flow techniques were used to detect the expression of key proteins involved in downstream autophagy and apoptosis. We found that when PI3K inhibitors were activated, apoptosis decreased, the levels of autophagy-positive proteins LC3-I/LC3-II and Bcl-1 increased, the levels of autophagy-negative protein P62 decreased, the levels of pro-apoptotic proteins Bax and caspase-3 decreased, the levels of the apoptosis-inhibiting protein Bcl-2 increased. In contrast, when a PI3K activator was used, autophagy was inhibited, and apoptosis was increased. This study revealed the effect of CCL2 on autophagy and apoptosis after SCI through the PI3K/Akt/mTOR signaling pathway. By blocking the expression of the autophagy-related gene CCL2, the autophagic protective response can be activated, and apoptosis can be inhibited, which may be a promising strategy for the treatment of SCI.

Serum levels of immunoglobulins in an adult population and their relationship with nonalcoholic fatty liver disease.

OBJECTIVES: Few studies have reported the association between nonalcoholic fatty liver disease (NAFLD) and immunoglobulins. In this study, we aimed to investigate the relationship between serum immunoglobulin levels and NAFLD in a Chinese adult population. METHODS: We performed a cross-sectional study including 11 261 Chinese adults. NAFLD was diagnosed based on the Chinese Guidelines for the diagnosis and treatment of fatty liver diseases and an alcohol intake of <70 g/week in women and <140 g/week in men, and serum immunoglobulin (Ig) levels were determined using immune nephelometry. Multiple logistic regression analysis was done to assess relationships between concentrations of serum immunoglobulins and NAFLD. RESULTS: Of the 11 261 adults recruited from January 2010 to December 2015, the prevalence of NAFLD was 40.8% (n = 4598). The geometric mean levels of IgG, IgM, IgE and IgA were 1177.49 mg/dL (95% confidence interval [CI] 1173.07-1181.93), 93.56 mg/dL (95% CI 92.70-94.42), 30.70 IU/mL (95% CI 29.92-31.49) and 216.64 mg/dL (95% CI 214.95-218.34), respectively. Compared with the lowest quintile, the multivariable adjusted odds ratio (95% CI) of NAFLD for the highest quintile of IgG, IgM, IgE, and IgA were 0.78 (0.66-0.92), 0.71 (0.60-0.84), 0.98 (0.84-1.15) and 1.41 (1.21-1.66), respectively. CONCLUSION: Increased IgA and decreased IgG and IgM levels are independently associated with NAFLD prevalence. Further research is needed to explore the causal association between serum immunoglobulins and NAFLD.

[Clinical effects of internal fixation with Herbert screws for the treatment of Pipkin femoral head fractures].

OBJECTIVE: To explore the therapeutic effects of internal fixation with Herbert screws for the treatment of Pipkin type I and type II femoral head fractures. METHODS: From January 2008 to December 2012, 23 patients with Pipkin type I and type II femoral head fractures were treated with open reduction and internal fixation by Herbert screws through Kocher-Langenbeck approach. Twenty-three patients (aged 18 to 52 years with a mean of 35.5 years, including 18 males and 5 females patients, 8 left hips and 15 right hips) with femoral head fractures and posterior hip dislocation. The fracture was classified according to Pipkin classification based on the radiographic findings, 5 patients had type I and 18 had type II fractures. The duration time from admission to the operation ranged from 6 to 72 h (averaged 32 h). The clinical and radiographic outcomes of the patients were measured using Thompson-Epstein scoring scale. The Harris hip score(HHS) was used to evaluate and compare hip functions at the latest follow-up between affected and healthy sides. RESULTS: All the patients were followed up, and the duration ranged from 20 to 48 months (averaged 30 months). According to Thompson-Epstein system, 12 patients got an excellent result, 6 good, 4 fair and 1 poor. The average HHS at the finial follow-up was 87.80 ± 8.46 (ranged from 66 to 95), which is similar to that in the healthy side 90.10 ± 6.35 (ranged from 72 to 98) (t = 1.044, P = 0.302). The complications such as deep infection, and deep vein thrombosis were not found. At the 3rd year during follow-up,4 patients had avascular necrosis of femoral head. At the 1st year of follow-up, 1 patient had hip pain after walking,screws loosening and shift after trauma,and serious complications of traumatic arthritis. All the 5 patients were treated with total hip arthroplasties. CONCLUSION: The treatment of internal fixation with Herbert screws through the Kocher-Langenbeck approach is effective for Pipkin type I and type II femoral head fracture. The method is reliable and valuable for recommendation. However, such fracture may have avascular necrosis of femoral head and complication of traumatic arthritis, which should be observed carefully in clinic with preparation of the prevention and treatment measures.

[Treatment of fracture of fifth metatarsal base and degree III lateral ligament injury of ankle with compressed cannulated screw and suture anchors].

OBJECTIVE: To investigate the clinical outcomes of surgical treatment of fracture of the fifth metatarsal base combined with degree III lateral ligament injury of ankle. METHODS: From January 2008 to December 2011, 32 patients with fracture of the fifth metatarsal base combined with degree III lateral ligament injury of ankle were treated with surgery. Fractures were fixed with compressed canulated screw and ligaments were repaired with suture anchors. After operation, ankle joints were fixed in neutral position and slightly valgus position by plaster slab. Taking out stitch was performed at 2 weeks after operation and non-weight loading walking by double crutches support started; after the 6 weeks, remove the gypsum and part-weight loading walking by brace protection; at the 8 weeks after operation, completely weight loading walking was permitted. American Orthopaedic Foot and Ankle Society (AOFAS) was used to evaluate the clinical effect. RESULTS: Thirty-two patients were followed up from 8 to 18 months with an average of 12 months. All fractures obtained healing with an average time of 12.5 weeks (ranged, 8 to 24 weeks). According to the standard of AOFAS, 18 cases got excellent results and 14 good. CONCLUSION: The method that fracture fixation with compressed canulated screw and ligament repair with suture anchors can obtain satisfactory effects in treating fracture of the fifth metatarsal base and degree III lateral ligament injury of ankle.