A hippocampus dependent neural circuit loop underlying the generation of auditory mismatch negativity.

Extracting relevant information and transforming it into appropriate behavior, is a fundamental brain function, and requires the coordination between the sensory and cognitive systems, however, the underlying mechanisms of interplay between sensory and cognition systems remain largely unknown. Here, we developed a mouse model for mimicking human auditory mismatch negativity (MMN), a well-characterized translational biomarker for schizophrenia, and an index of early auditory information processing. We found that a subanesthetic dose of ketamine decreased the amplitude of MMN in adult mice. Using pharmacological and chemogenetic approaches, we identified an auditory cortex-entorhinal cortex-hippocampus neural circuit loop that is required for the generation of MMN. In addition, we found that inhibition of dCA1→MEC circuit impaired the auditory related fear discrimination. Moreover, we found that ketamine induced MMN deficiency by inhibition of long-range GABAergic projection from the CA1 region of the dorsal hippocampus to the medial entorhinal cortex. These results provided circuit insights for ketamine effects and early auditory information processing. As the entorhinal cortex is the interface between the neocortex and hippocampus, and the hippocampus is critical for the formation, consolidation, and retrieval of episodic memories and other cognition, our results provide a neural mechanism for the interplay between the sensory and cognition systems.

IRAK-4 in macrophages contributes to inflammatory osteolysis of wear particles around loosened hip implants.

TLRs recognizing PAMPS play a role in local immunity and participate in implant-associated loosening. TLR-mediated signaling is primarily regulated by IL-1 receptor associated kinase-M (IRAK-M) negatively and IRAK-4 positively. Our previous studies have proved that wear particles promote endotoxin tolerance in macrophages by inducing IRAK-M. However, whether IRAK-4 is involved in inflammatory osteolysis of wear particles basically, and the specific mechanism of IRAK-4 around loosened hip implants, is still unclear. IRAK-4 was studied in the interface membranes from patients in vivo and in particle-stimulated macrophages to clarify its role. Also, IL-1ß and TNF-α levels were measured after particle and LPS stimulation in macrophages with or without IRAK-4 silenced by siRNA. Our results showed that the interface membranes around aseptic and septic loosened prosthesis expressed more IRAK-4 compared with membranes from osteoarthritic patients. IRAK-4 in macrophages increased upon particle and LPS stimulation. In the former, IL-1ß and TNF-α levels were lower compared with those of LPS stimulation, and IRAK-4 siRNA could suppress production of pro-inflammatory cytokines. These findings suggest that besides IRAK-M, IRAK-4 also plays an important role in the local inflammatory reaction and contributes to prosthesis loosening.

[Analysis of the clinical effects of the modified halo pelvic frame for the treatment of severe scoliosis with rigidity].

OBJECTIVE: To evaluate the clinical curative effect of the modified Halo pelvic frame and surgery for the treatment of severe scoliosis with rigidity. METHODS: From January 2004 to May 2010,50 patients with severe scoliosis patients with rigidity were treated in our hospital. Twenty-three patients were male and 27 patients were female, with a mean age of 10.8 years old, ranging from 4 to 16 years. Twenty-four patients were congenital scoliosis and 26 patiens were idiopathic scoliosis. The mean body height were (152.1 +/- 11.1) cm and the average Cobb angle of scoliosis and kyphosis were (91.8 +/- 14.5) degrees and (69.5 +/- 14.0) degrees respectively. All the patients were treated with three-stages modified Halo pelvic traction, the second stage anterior release and the third stage posterior correction. The amount of correction was determined by measuring the change of body height, the Cobb angles and correction rate of scoliosis as well as kyphosis before and after the operation. RESULTS: The mean body height were correct to (158.5 +/- 10.5) cm. The average Cobb angle of scoliosis were correct to (30.8 +/- 7.9) degrees. The average Cobb angle of kyphosis were correct to (31.6 +/- 10.1) degrees. After the first stage, the average Cobb angle of scoliosis and kyphosis were changed with the mean of (30.4 +/- 6.6)% correction and (22.3 +/- 5.2)% respectively; after the second stage, the average Cobb angle of scoliosis and kyphosis were changed with the mean (26.7 -/+ 5.1)% correction and (21.2 -/+ 6.0)% respectively; the third stage, above data were (33.7 -/+ 7.2)% and (27.1 +/- 5.3)%. Correction rate of scoliosis and kyphosis were (66.5 +/- 7.2)% and (55.1 +/- 6.4)% respectively by the modified Halo pelvic frame traction and surgery. Body height, the Cobb angles and correction rate of scoliosis and kyphosis on radiographs were different in all stages (P<0.05). CONCLUSION: Operative complications of severe scoliosis with rigidity can be reduced and better deformity correction and trunk balance achieved by the modified Halo pelvic frame traction and surgery.