OTULIN of exosomes derived from Schwann cells promotes peripheral nerve injury repair by regulating macrophage polarization via deubiquitination of ERBB2.

A significant public health burden is peripheral nerve damage (PNI), which is frequently brought on by trauma. Macrophages were essential to the effective regeneration of nerves and restoration of function. It is still not entirely understood how macrophages and Schwann cells interact after damage during remyelination. Here, we established an inflammatory model in bone marrow-derived macrophages (BMDMs) and a rat sciatic nerve damage model to investigate the possible relationship between lipopolysaccharides (LPS)-induced exosomes derived from Schwann cells (LPS SCs-Exos) and peripheral nerve repair. The pro-inflammatory macrophage was changed into a pro-regeneration macrophage by LPS SC-Exos. Notably, it was discovered that SC-Exos had a substantial enrichment of OTULIN. OTULIN was a key mediator in the regulatory effects of LPS SC-Exos by deubiquitinating ERBB2 and preventing its degradation. The local injection of SC-Exos into the nerve damage site led in a faster functional recovery, axon regeneration and remyelination, and an increased M2 macrophage polarization, whereas OTULIN knockdown reversed these effects in vivo. Our results indicate that LPS SC-Exos may offer a therapeutic avenue for peripheral nerve regeneration by promoting macrophage polarization toward an M2 phenotype through the shuttling of OTULIN and deubiquitination of ERBB2. SIGNIFICANCE STATEMENT: OTULIN protein from SC-Exos mediated the macrophages polarization and axonal growth in BMDMs through promoting ubiquitination of ERBB2 and triggering the degradation of ERBB2. The findings offered prospective therapeutic hints for PNI therapy approaches that target axonal regrowth.

Case Report: Rheumatoid meningitis with positive NMDAR antibody: A case treated with intravenous immunoglobulin.

As a rare complication of rheumatoid arthritis (RA) in the central nervous system (CNS), rheumatoid meningitis (RM) mainly affects the meninges and has various clinical symptoms. The diagnostic and treatment approaches currently used are not practical. RM cases with positive NMDAR antibodies (Abs) have never been reported. In the present study, a 66-year-old man with a 1-year history of RA presented recurrent left lower limb weakness during activities for 1 month. The results showed that rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) were positive in the serum, and NMDAR Abs were present in cerebrospinal fluid (CSF). Hyperintensity was observed in the leptomeninges of the right frontal and parietal lobes, and subtle hyperintensity was observed in the left frontal and parietal lobes, as indicated by brain MRI. A meningeal biopsy revealed non-specific inflammation with the absence of rheumatoid nodules. The patient was given IVIg on day 7 after admission. The clinical symptoms were relieved, the lesions were alleviated, and abnormal biochemical indicators were gradually recovered 1 week after initiation of the treatment, while NMDAR Abs were present in CSF even after treatment. After 5 months of follow-up, the patient's serum and CSF ACPA and IL-6 levels were still high. The findings showed that brain MRI was adequate for the diagnosis of RM. ACPA and IL-6 might be the specific biomarkers for disease activity in RM. IVIg was effective as induction therapy for RM. Further studies should explore whether the presence of NMDAR Abs is associated with RM.

Design of Optimization Algorithm for Configuration of Amateur Sports Training Equipment in Smart City Community.

Community amateur sports training equipment is necessary to ensure the development of national fitness activities. It is found that the design concept of community public sports space in China is not perfect, the structural layout is not reasonable, the stock space is not optimized, and the resource allocation is not balanced. In particular, there is a lack of indoor fitness facilities and sports venues in the community, and the people's "fitness where to go" is still a difficult problem. In the smart city construction, the resource integration and optimization of community amateur sports training facilities have also been further developed. Considering various influencing factors, this paper establishes a location model of community amateur sports training facilities with the least total cost and convenience. Aiming at the practical optimization problem with high complexity, an improved adaptive weight multiobjective particle swarm optimization (PSO) model is proposed. These parameters in the algorithm were adjusted dynamically, which balanced the overall search ability and partial improvement ability of the PSO algorithm and completed the optimal scheduling of community amateur sports training equipment configuration while ensuring the optimal global solution. Experimental results show that the algorithm's efficiency and searching ability have been further promoted. It also has an excellent performance in solving the complex location problem of community amateur sports training facilities.

Therapeutic hypothermia (different depths, durations, and rewarming speeds) for acute ischemic stroke: a meta-analysis.

OBJECTIVES: Whether therapeutic hypothermia benefits patients with acute ischemic stroke (AIS) remains controversial. The aim of this study was to evaluate the efficacy and safety of the different depths, durations, and rewarming speeds of therapeutic hypothermia for AIS. METHODS: The MEDLINE (OVID), EMBASE, and Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) of therapeutic hypothermia for AIS from the inception of the databases to October 2013. After data extraction and quality assessment, a meta-analysis was performed using RevMan 5.1. RESULTS: A total of 6 RCTs involving 252 AIS patients were eligible for the meta-analysis. Subanalyses stratified by depth, duration, and rewarming speed of therapeutic hypothermia were also performed. Our results showed that therapeutic hypothermia was associated with an increased risk of pneumonia (risk ratio = 3.30, 95% CI 1.48-7.34; P = .003, P for heterogeneity = .91, I(2) = 0%). No significant difference was observed between the 2 groups in terms of neurologic outcomes, mortality, and other complications including symptomatic or fatal intracranial hemorrhage, deep vein thrombosis, and atrial fibrillation. CONCLUSIONS: These limited data suggest that therapeutic hypothermia does not significantly improve stroke outcomes and may lead to higher rates of pneumonia. Multicenter RCTs with larger samples are needed to confirm the current findings.