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Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for spinal cord injury, but immunological rejection and possible tumor formation limit its application. The therapeutic effects of MSCs mainly depend on their release of soluble paracrine factors. Exosomes are essential for the secretion of these paracrine effectors. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-EXOs) can be substituted for BMSCs in cell transplantation. However, the underlying mechanisms remain unclear. In this study, a rat model of T10 spinal cord injury was established using the impact method. Then, 30 minutes and 1 day after spinal cord injury, the rats were administered 200 μL exosomes via the tail vein (200 μg/mL; approximately 1 × 106 BMSCs). Treatment with BMSC-EXOs greatly reduced neuronal cell death, improved myelin arrangement and reduced myelin loss, increased pericyte/endothelial cell coverage on the vascular wall, decreased blood-spinal cord barrier leakage, reduced caspase 1 expression, inhibited interleukin-1β release, and accelerated locomotor functional recovery in rats with spinal cord injury. In the cell culture experiment, pericytes were treated with interferon-γ and tumor necrosis factor-α. Then, Lipofectamine 3000 was used to deliver lipopolysaccharide into the cells, and the cells were co-incubated with adenosine triphosphate to simulate injury in vitro. Pre-treatment with BMSC-EXOs for 8 hours greatly reduced pericyte pyroptosis and increased pericyte survival rate. These findings suggest that BMSC-EXOs may protect pericytes by inhibiting pyroptosis and by improving blood-spinal cord barrier integrity, thereby promoting the survival of neurons and the extension of nerve fibers, and ultimately improving motor function in rats with spinal cord injury. All protocols were conducted with the approval of the Animal Ethics Committee of Zhengzhou University on March 16, 2019.

Background: Alcohol dependence, a global public health problem, leads to structural and functional damage in the brain. Alcohol dependence patients present complex and varied clinical manifestations and live with general complaints existing in contemporary society, making most people with alcohol dependence hard to identify. Therefore, it is important to find potential biomarkers for the diagnosis and evaluation of alcohol dependence. In the study, we explored potential biomarkers for the diagnosis and monitoring of diseases and evaluated brain structural changes in alcohol dependence patients.Methods: Enzyme-linked immunosorbent assay (ELSA) was employed to detect the expression of serum nucleotide-binding oligomerization domain containing 3 (NLRP3) and single-molecule array (Simoa) assay was used to detect the expression of serum neurofilament light (NfL) in 50 alcohol dependence patients and 50 controls with no drinking history. Alcohol consumption was measured by standard drinks. Neuropsychological assessments, including the Montreal cognitive assessment (MoCA), Pittsburgh sleep quality index (PSQI), generalized anxiety disorder (GAD-7), and patient health questionnaire-9 (PHQ-9), were conducted to evaluate cognitive function and psychological state. The degree of white matter lesions (WMLs) was rated using the Fazekas scale based on magnetic resonance imaging analysis. White matter structure was quantified using the voxel-based morphometry method. The correlations between NLRP3 levels, NfL levels, neuropsychological dysfunction, the degree of WMLs, and white matter volume (WMV) were analyzed in alcohol dependence patients.Results: Serum NLRP3 and NfL levels were higher in the alcohol dependence group. NLRP3 levels were irrelevant to monthly alcohol assumption as well as to the MoCA, PSQI, GAD-7, PHQ-9, and Fazekas scale scores and WMV. NfL levels were positively correlated with the PSQI and PHQ-9 scores as well as the degree of WMLs and negatively correlated with the MoCA scores and WMV. No associations were evident between NfL and monthly alcohol assumption and GAD-7 scores in the alcohol dependence group.Conclusion: This study supports the potential value of serum NfL as a non-invasive biomarker in alcohol dependence. The association with neuropsychological dysfunction and degree of WMLs has implications to use NfL as a promising biomarker to assess the severity of brain damage as well as the progression and prognosis of alcohol dependence.

In this paper, the mechanical properties and corrosion behavior of steel/Al electromagnetic self-pieced riveting, adhesive and hybrid riveted and adhesive joints in the salt-spray environment were compared. These joints were firstly placed in the neutral salt spray environment, and then surface observation, weighting, mechanical properties tests and fractographic analysis were conducted. Results showed that with the increase of ageing time, the peak load of the single riveted joints firstly increased and then decreased, while the peak loads of the other two joints continued to decline. This was because the corrosion products formed in the sheet clearance of the single riveted joint, increasing the frictional resistance during the shear process after a short ageing time (before 20 days). For adhesive and hybrid joints, adhesives prevented the formation of corrosion products in the clearance, but it was vulnerable to damage by chloride ions, which would result in the continuous strength degradation of the joints. Specifically, after ageing for a long time (25 days), the peak load of the riveting, adhesive and hybrid joints, respectively, decreased by 11.2%, 26.3% and 14.4% comparing with the uncorroded joint, which showed the adhesive joint had the worst corrosion resistance. This indicated that the adhesive joint was more affected by environmental factors than the riveted and hybrid joint.

Neuromyelitis optica spectrum disorders (NMOSDs) are inflammatory diseases with a high risk of recurrence and progressive disability, and it is crucial to find sensitive and reliable biomarkers for prognosis and the early prediction of relapse. Highly active NMOSD is defined as two or more clinical relapses within a 12-month period. In this study, we analyzed independent risk factors among patients with aquaporin-4 (AQP4)-IgG positive highly active NMOSD. In this retrospective study, we analyzed the data of 94 AQP4-IgG positive patients with highly active NMOSD and 105 AQP4-IgG positive controls with non-highly active NMOSD. In order to rule out possible effects of previous treatments (such as glucocorticoids, immunoglobulin, and immunosuppressants), we focused on the first-attack NMOSD patients admitted to our hospital. Clinical data, including the age of onset, gender, comorbidities, and serum analysis and cerebrospinal fluid (CSF) analysis results, were collected, after which logistic regression models were used to determine the associations between the clinical factors and relapse outcomes. The prevalence of connective tissue disease and the proportion of antinuclear antibody (ANA)-positivity were higher in the highly active NMOSD group than in the control group. The leukocyte counts, homocysteine (Hcy) levels, CSF leukocyte counts, protein concentrations, IgG indexes, and 24h IgG synthesis rates were also higher in the highly active NMOSD group. The results of multivariate analysis indicated that connective tissue disease comorbidity (OR = 5.953, 95% CI: 1.221–29.034, P = 0.027), Hcy levels (OR = 1.063, 95% CI: 1.003–1.126, P = 0.04), and 24h IgG synthesis rate (OR = 1.038, 95% CI: 1.003–1.075, P = 0.034) may be independent risk factors for AQP4-IgG positive highly active NMOSD relapse after adjusting for various variables. Comorbidity of connective tissue disease, Hcy levels, and 24h IgG synthesis rate may be independent risk factors for AQP4-IgG positive highly active NMOSD.

Background The aim of this study was to investigate the feasibility of using a combination of apatinib in the treatment of non-small cell lung cancer. Apatinib is a tyrosine kinase inhibitor which selectivelyacts on vascular endothelial growth factor receptor 2 (VEGFR-2) and has shown good efficacy in a variety of malignancies, but the drug resistance is fast in single drug therapy. Methods The inhibitory effect of apatinib and other drugs on lung cancer cells was determined by CCK-8 test in vitro, and the IC50 value was determined. To establish a nude mouse xenograft model, observe the inhibitory effect of apatinib combined with other drugs on lung cancer xenografts in nude mice; immunohistochemical staining of tumor microvessel density and Ki67 expression in transplanted tumor tissues; Western blot analysis of related signaling pathways expression; immunohistochemistry was used to detect tumor microvessel density in other organs and to observe its safety. Results In this study, we found apatinib combined with pemetrexed, the first and third generation of epidermal growth factor receptor tyrosine kinase inhibitor, could synergistically inhibit the proliferation of non-small cell lung cancer cell (NSCLC) lines, reduce the microvessel density and Ki67 protein levels of three non-small cell lung cancer xenografts, and enhance anti-tumor activity by synergistically inhibiting the MAPK-ERK and PI3K-AKT-mTOR signaling pathway. Furthermore, there were no pathological abnormalities in the heart, brain, liver and kidney of each group. Conclusions The efficacy of apatinib combination is better than that of monotherapy, and there is no significant difference in toxicity of important organs, which suggests the feasibility of a combination of apatinib in the treatment of non-small cell lung cancer.

Ischemic stroke is one of the main central nervous system diseases and is associated with high disability and mortality rates. Recombinant tissue plasminogen activator (rt-PA) and mechanical thrombectomy are the optimal therapies available currently to restore blood flow in patients with stroke; however, their limitations are well recognized. Therefore, new treatments are urgently required to overcome these shortcomings. Recently, stem cell transplantation technology, involving the transplantation of induced pluripotent stem cells (iPSCs), has drawn the interest of neuroscientists and is considered to be a promising alternative for ischemic stroke treatment. iPSCs are a class of cells produced by introducing specific transcription factors into somatic cells, and are similar to embryonic stem cells in biological function. Here, we have reviewed the current applications of stem cells with a focus on iPSC therapy in ischemic stroke, including the neuroprotective mechanisms, development constraints, major challenges to overcome, and clinical prospects. Based on the current state of research, we believe that stem cells, especially iPSCs, will pave the way for future stroke treatment.

BackgroundIt is difficult to predict lymph node metastasis in patients with early lung cancer. Pure ground glass opacity (GGO) on computed tomography indicates an early-stage adenocarcinoma that can be removed by limited resection or lobectomy without the need for mediastinal lymph node dissection or sampling, and lung adenocarcinoma with GGO therefore has a good prognosis. We examined the incidence and risk factors of lymph node metastasis in patients with clinical stage IA lung adenocarcinoma.MethodsWe retrospectively analyzed clinical data for 327 patients with stage IA peripheral lung cancer treated in our hospital from March 2014 to December 2018. The patients were divided into four groups according to computed tomography signs. Lobectomy and systematic lymph node dissection were performed in all patients. Correlations between lymph node metastasis and clinical pathological factors were analyzed by logistic regression.ResultsAmong the 327 patients, 26 (7.95%) had lymph node metastasis. No patients with pure GGO or GGO-dominant types had lymph node metastasis. Logistic regression identified tumor diameter, solid content, plasma carcinoembryonic antigen (CEA) level, pathological type, lymphovascular invasion, and pleural invasion as factors related to the presence of lymph node metastasis.ConclusionsTumor diameter, solid component ratio, plasma CEA level, pathological type, vascular tumor thrombus, and pleural invasion are possible independent risk factors for lymph node metastasis in patients with stage IA lung adenocarcinoma. In contrast, lymph node metastasis is rare in patients with pure GGO or GGO-dominant lung adenocarcinoma.

Antibiotics have been widely used in the past decades and caused global public health concerns due to the growing problems of antimicrobial resistance. The peri-urban rivers are always receiving massive wastes containing antibiotics and appear to be a reservoir of antibiotics and antibiotic resistance genes in the environment. To prevent and control the pollution of antibiotics, it is essential to correctly identify the potential sources of antibiotics in peri-urban rivers. Currently, systematic knowledge on risk characteristics and source apportionment of antibiotics in peri-urban rivers is still lacking. In the study, we addressed this problem and focused on exploring the ecotoxicological risk and potential sources of antibiotics in a peri-urban river in Beijing (Chaobai River). To this end, the waters and sediments were collected from the river, as well as the potential source types including domestic sewage, WWTP effluent, chicken manure, pig manure and cattle manure. The occurrence and concentration levels of 16 antibiotics in the waters and sediments of the river were comprehensively characterized, as well as the correlation of antibiotics with environmental factors. Then, risk quotients and mixture risk quotients were used to assess the ecotoxicological risk of single compound and the mixture toxicity of antibiotics, respectively. The synergistic effects of antibiotic mixtures were also analyzed. Further, positive matrix factorization was employed to apportion the potential sources of antibiotics based on the multilinear engine (ME-2) algorithm. The target antibiotics were widely detected in the peri-urban river and several antibiotics posed moderate ecotoxicological risks on aquatic organisms. Apportionment analysis identified four potential sources of antibiotics in the waters of Chaobai River, including domestic sewage (31.5%), chicken waste (26.4%), WWTP effluent (22.2%) and a mix source (20.0%). Additionally, WWTP effluent (~58%) and sewage effluent (41%) were apportioned as the main contributors of antibiotics in the sediments.

As a result of the widespread use of antibiotics, a large amount of excretion from human and animals containing antibiotic residues was discharged into the environment with wastewaters and manures, leading to potential adverse effects on ecosystem health. To understand the environmental fate of antibiotics, a dynamic level IV fugacity model was established here by introducing the novel process of nondiffusive wastewater irrigation from water to soil, and applied to a large-scale water-scarce region, the megacity Beijing. Furthermore, a Monte-Carlo based risk assessment approach was employed to evaluate the potential risks posed by antibiotics in water, sediment and soil, combined with the soil-water equilibrium partitioning method. Model validation, sensitivity and uncertainty analysis suggests that the fugacity model can successfully simulate the reported concentration data within an average difference of 0.2 logarithmic units. Results showed that more than one hundred tonnes of antibiotics were estimated to be discharged into the environment of Beijing in 2013, and, resulted in high antibiotics levels and posed high potential risks on the aquatic environment. On the other hand, although wastewater irrigation increased the antibiotics concentrations in soil and even dominated the total transfer fluxes, the overall risk levels of antibiotics in the soil were acceptable.

Background B-cell subset in the peripheral blood is widely recognized as a monitoring indicator of repeated rituximab (RTX) infusion timing in clinical studies of Neuromyelitis Optica Spectrum Disorder (NMOSD). However, its threshold is undetermined and may vary individually. Case presentation We report two cases of NMOSD treated with low-dose RTX with long-term follow-up. In the two cases, the patients kept relapse-free status in most of the time points with pre-specified repeated RTX infusions, no matter the percentage of total B cell (CD19+) was above 1%, or memory B-cell (CD19+CD27+) was above 0.05% in the initial two years and 0.1% thereafter, as previously proposed in most of studies. Conclusions The two cases raise the question whether the level of B-cell is an indicator for repeated RTX infusion. Re-defining optimal indicators for repeated RTX infusion in NMOSD will be meaningful for reducing potential long-term adverse reactions of this treatment, as well as gaining a more cost-effective result.

Aims Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by widespread inflammation. LncRNA taurine-up-regulated gene 1 (TUG1) has been reported to be involved in multiple biological processes and human diseases. The aim of this study was to investigate the role of lncRNA TUG1 in MS and the underlying mechanism. Main methods Experimental autoimmune encephalomyelitis (EAE) was induced in mice by immunization with myelin oligodendrocyte glycoprotein peptide 35–55 (MOG35–55). Lentiviral vectors encoding sh-TUG1 was constructed to silence TUG1 in MOG-EAE mice by intracerebroventricular (ICV) injection. The effect of TUG1 on inflammation in MS was evaluated by real-time PCR, Western blot, ELISA and Hematoxylin-eosin staining. To further study the mechanism of TUG1 in MS, TUG1 knockdown and miR-9-5p overexpression were performed in LPS-induced BV2 cells. Key findings Down-regulation of TUG1 improved mice behavior, reduced granulocyte-macrophage colony stimulating factor (GM-CSF) level, decreased the levels of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-6 and IL-17, and increased IL-10 in EAE mice. Notably, TUG1 expression was negatively correlated with miR-9-5p expression, while positively correlated with NF-κB1/p50. Knockdown of TUG1 or enforced expression of miR-9-5p inhibited LPS-induced inflammation in BV2 cells, while these effects were abolished by inhibition of miR-9-5p. We further verified that TUG1 negatively regulated miR-9-5p expression and NF-κB1/p50 is a direct target of miR-9-5p. Significance Down-regulation of TUG1 attenuates MS through inhibition of inflammation by sponging miR-9-5p via targeting NF-κB1/p50, suggesting that TUG1 is a potential therapeutic target for MS treatment.

In the tumor vascular system, the vascular structure is disordered, the morphology is abnormal, and the structure of the blood vessel walls is incomplete, leading to leakage of the blood vessel wall, elevated interstitial fluid pressure, and elevated blood flow resistance. These alterations lead to local microenvironmental changes, which mainly manifest as a lack of oxygen and acidosis, further affecting the efficacy of chemotherapy drugs. Antiangiogenic drugs can normalize the abnormalities caused by tumor angiogenesis, thereby transferring oxygen and drugs to tumor cells more efficiently through normalized blood vessels and enhancing the efficacy of chemotherapy drugs. Apatinib is a specific VEGFR‐2 inhibitor that blocks the transmission of the VEGF/VEGFR‐2 signaling pathway. In this study, we constructed a nude mouse xenograft model of lung cancer and administered apatinib at different doses and times to detect the normalization of reactive blood vessels through VEGF, α‐SMA, college‐IV, HIF‐1α, and MMP. The ultrastructure of tumor blood vessels was observed by electron microscopy, and the dose and timing of apatinib‐induced normalization of lung cancer in nude mice were confirmed. Then, we observed the inhibitory effect of apatinib combined with pemetrexed on transplanted tumors of lung cancer cells in nude mice at different time points and observed whether combination pemetrexed chemotherapy showed more significant effects in the time window of vascular normalization induced by apatinib. The inhibition of the growth of transplanted tumors was examined. Then 20 patients with advanced non–small cell lung cancer were enrolled, and apatinib sequential chemotherapy drugs were applied as a third‐line chemotherapy regimen to observe its clinical efficacy., In this work, we confirmed that low doses of apatinib can induce tumor vascular normalization within a certain period of time, and combined chemotherapy can improve the therapeutic effect during this period of time.

Background N-acetylcysteine is a classic mucolytic agent. This study aimed to investigate the efficacy of N-acetylcysteine on reducing the risk of exacerbations in bronchiectasis patients. Methods A prospective, randomized, controlled trial was conducted between April 1, 2014 and December 31, 2016 in five general hospitals in Shandong Province, China. Adult bronchiectasis patients with at least two exacerbations in the past year were potentially eligible. Patients were randomly assigned to receive oral N-acetylcysteine (600 mg, twice daily, 12 months) or on-demand treatment. Results A total of 161 patients were eligible for randomization (81 to the N-acetylcysteine group and 80 to the control group). During the 12-month follow-up, the incidence of exacerbations in the N-acetylcysteine group was significantly lower than that in the control group (1.31 vs. 1.98 exacerbations per patient-year; risk ratio, 0.41; 95% CI, 0.17–0.66; P = 0.0011). The median number of exacerbations in the N-acetylcysteine group was 1 (0.5–2), compared with 2 (1–2) in the control group (U = − 2.95, P = 0.003). A total of 24.7% of the N-acetylcysteine group patients and 11.3% of the control group patients remained exacerbation-free throughout the 12-month follow-up (χ 2 = 4.924, P = 0.026). Compared with the control group, the volume of 24-h sputum in the N-acetylcysteine group was significantly reduced (t = − 3.091, P = 0.002). Additionally, the N-acetylcysteine group showed a significant improvement in the quality of life. No severe adverse events were reported in the intervention group. Conclusion The long-term use of N-acetylcysteine is able to reduce the risk of exacerbations for bronchiectasis patients in Shandong Province, China. The results of this study should be verified in a larger randomized controlled trial. Trial registration ClinicalTrials.gov (NCT02088216) (Registered date: March 5, 2014).

Lung adenocarcinoma (LUAD) is one of the most lethal malignancies, posing a threat to human health. However, the molecular mechanisms underlying LUAD development remain largely unknown. In this study, we found that miR-1-3p was significantly downregulated in human LUAD tissues and cell lines and played an inhibitory role in LUAD cell tumorigenesis, as evidenced by the significantly reduced viability, migration, and invasion of LUAD cells in response to miR-1-3p overexpression. Mechanistically, microRNA (miR)-1-3p physically interacted with the 3'-untranslated region (UTR) of protein regulator of cytokinesis 1 (PRC1) mRNA, leading to downregulation of PRC1. Overexpression of PRC1 reversed the inhibitory effects of miR-1-3p on LUAD cell tumorigenesis, suggesting that the miR-1-3p/PRC1 axis is majorly involved in suppressing LUAD development and progression. Consistently, PRC1 was dramatically induced in LUAD tissues and cell lines as well as associated with a poor prognosis in LUAD patients. Taken together, our study identified the miR-1-3p/PRC1 axis as an important regulatory mechanism contributing to LUAD inhibition and provided valuable clues for the future development of therapeutic strategies against LUAD.

Eighty-eight ischemic stroke patients with massive cerebral infarction (MCI) who met our selection criteria were included in this study. MCI was assessed using the Glasgow Coma Scale (GCS) at hospital admission and at 2 weeks. The sera of all patients and controls were sampled at 48 h after the patients' attacks, and the sera of patients with MCI who had no severe cardiopulmonary complications, including those with hemorrhagic transformation (HT), were sampled again at 2 weeks. The relative expression of let-7 miRNA in the serum was determined by real-time qRT-PCR, and the blood levels of lipids, glucose, high-sensitivity C-reactive protein (hs-CRP), homocysteine and blood pressure were measured at admission. Interleukin-6 (IL-6) levels were detected by ELISA, and a luciferase assay was performed to confirm that IL-6 was a gene target of let-7. The relative expression of let-7f was significantly down-regulated in MCI without HT patients compared with controls (P

Antibiotics and antibiotic resistance genes in the river system have received growing attention in recent years due to their potential threat to aquatic ecosystems and public health. Recognizing the occurrence and distribution of antibiotics in river environment and assessing their ecological risks are of important precondition for proposing effective strategies to protect basin safety. In this study, a comprehensive investigation was conducted to identify the contamination and risk characteristics of antibiotics in the aquatic environment of Hai River system (HRS) which is the largest water system in northern China. To attain this objective, several tools and methods were considered on the data set of water and sediment samples collected in the past ten years. The occurrence pattern, concentration levels and spatiotemporal distribution of antibiotics in the HRS were characterized utilizing statistical and comparative analysis. Risk quotients were employed to assess the adverse ecology effects caused by single antibiotic or their mixtures. Screening tool with priority factor and accumulation growth factor was used auxiliarily to prioritize antibiotics that should be of highly concern. Results indicated that the occurrence frequencies and concentration levels of 16 representative antibiotics in HRS were generally higher than those reported in global waters. Most antibiotics showed significant seasonal and spatial variations. Comparatively speaking, sulfamethoxazole, norfloxacin, erythromycin and roxithromycin posed higher risks to aquatic organisms in the HRS individually, and the combination of tetracycline and enrofloxacin indicated synergistical actions. Overall, due to their potential risks, considerable levels or quick increasing trends, 13 antibiotics were identified as priority contaminants in the HRS and should be paid special attention to be strictly regulated in the future.

microRNAs are a class of non-coding RNAs including approximately 22 nucleotides in length and play a pivotal role in post-transcriptional gene regulation. Currently, the role of miRNAs in the pathophysiology of ischemic stroke has been the subject of recent investigations. In particular, antagomirs to microRNA (miRNA) let-7f have been found to be neuroprotective in vivo, although the detailed function of let-7f during cerebral ischemia has not been fully illustrated. NDRG3 is an N-myc downstream-regulated gene (NDRG) family member that has been observed in the nuclei in most brain cells. Recently, a NDRG3-mediated lactate signaling, in which stabilized NDRG3 protein can promote angiogenesis and cell growth by activating the Raf-ERK pathway in hypoxia was discovered. In this study, we preliminarily explored the change in the expression of the NDRG3 protein which indicated that NDRG3 protein is an oxygen-regulated protein in neurons in rat cerebral ischemia in vivo and in vitro. We further identified let-7f as an upstream regulator of NDRG3 by the lentiviral transfection of rat cortical neurons and the dual luciferase analysis of human genes. In addition, a dual-color fluorescence in situ hybridization assay showed that when the expression of let-7f was elevated, the expression of NDRG3 mRNA was accordingly reduced in rat cerebral ischemia. Taken together, our results identify a new regulatory mechanism of let-7f on NDRG3 expression in the hypoxic response of cerebral ischemia and raise the possibility that the let-7f/NDRG3 pathway may serve as a potential target for the treatment of ischemic stroke.

Down syndrome cell adhesion molecule (DSCAM) plays important roles in the regulation of synaptogenesis, neurite outgrowth, axon guidance and synapse formation. Overexpression of DSCAM in Down syndrome (DS) may be involved in the pathogenesis of mental retardation through an inhibitory action on synaptogenesis/neurite outgrowth, and in the precocious dementia associated with an amyloid precursor protein (APP) dosage effect with enhanced plaque formation. In this report we examined the expression of DSCAM in the cerebral cortex of APP transgenic mice versus age-matched wild-type mice. We found that the level of DSCAM expression increased with increasing age in both groups of mice, up to a maximum at 3 months old. The level of DSCAM expression in APP transgenic mice was significantly higher than in the age-matched wild types. We propose that overexpression of DSCAM in the cerebral cortex might play an important role in the learning and memory defects of APP transgenic mice.

Few studies have examined the relationship between mircroRNAs and moyamoya disease (MMD). We performed a study of the significance of let-7c expression in the serum of MMD patients.The experimental group includes 49 MMD patients, and the control group consists of 30 normal people, 20 cerebral hemorrhage patients, 20 massive cerebral infarction patients, 20 nonmassive cerebral infarction patients, and 20 neurological autoimmune disease patients. Let-7 family levels were determined by polymerase chain reaction. A dual luciferase assay was used to test whether let-7c recognized the 3'UTR of RNF213.The expression level of let-7c in MMD patients is higher than that observed in the control groups (P.001). The luciferase assay results indicated that hsa-let-7c could diminish luciferase activity from a reporter vector containing the 3'-UTR of RNF213 (P.05). The suppression of luciferase activity is not found in mutRNF213 (P.05).Increased expression of let-7c in MMD patients may contribute to MMD pathogenesis by targeting RNF213. Thus, let-7c may be a potential biomarker for the diagnosis of MMD.

Anti- N-methyl-d-aspartate (NMDA) receptor encephalitis is a new category of autoimmune encephalitis associated with anti-NMDA receptor antibodies. The disease was first described in 2007, and it predominantly affects young women with or without ovarian teratomas. Most patients typically present with seizures, a decreased consciousness level, dyskinesia, autonomic dysfunction, and psychiatric symptoms. The presence of anti-thyroid antibodies in non-tumor-associated anti-NMDA receptor encephalitis was first described in 2010. Additionally, anti-thyroid antibodies were found in teratoma-associated anti-NMDA receptor encephalitis. We report the cases of 3 Chinese girls with non-tumor-associated anti-NMDA receptor encephalitis with positive anti-thyroid antibodies. We followed up the details of their titers and suggest that anti-thyroid antibodies were an indicator of autoimmune predisposition in the development of non-tumor-associated anti-NMDA receptor encephalitis.