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??Abstract?? Objective To identify the clinical features and the prognosis of anti-NMDAR encephalitis in children??so as to improve the pediatrician’s awareness about this disease. Methods The clinical features??therapeutic regimen and prognosis of 17 children with anti-NMDAR encephalitis were summarized by a retrospective and follow-up study. Results Among the 17 patients with anti-NMDAR encephalitis??12 were males and 5 were females.Their age varied from 2 to 12 years??and the average age was 5 years 8 months.The most common initial symptoms were convulsions ??7 cases?? and psychiatric symptoms ??7 cases??.The common symptoms in the course of the disease were psychiatric symptoms??17 cases????sleep disorders ??16 cases????extrapyramidal symptoms ??14 cases????and convulsion ??11 cases??.Only 4 patients had autonomic symptoms.The anti-NMDAR antibody were found in all the patients’CSF.The EEG test of 16 patients showed diffused slow background.Tumors were not found in any patient. Fourteen cases were treated with IVIg and methylprednisolone??2 cases only received IVIg therapy and 1 case gave up.Rituximab ??2 cases?? and cyclophosphamide ??1 cases?? were administrated in 3 cases with no improvement after the above treatment.The patients had been followed up for 3 to 15 months.Twelve of them recovered completely??2 cases died??2 cases had epilepsy??and 1 case had speech disorder. Conclusion Psychiatric symptoms??sleep disorders??extrapyramidal symptoms and convulsion are the common symptoms of anti-NMDAR encephalitis in children.Tumors and autonomic nervous system dysfunction rarely happen. Immunotherapy is effective in the majority of the patients.The prognosis of anti-NMDAR encephalitis in children is optimistic.     

Induction of apoptosis by TPA and VP—16 is through translocation of TR3

AIM：To investigate the role of TR3 in induction of apoptosis in gastric cancer cells.METHODS:Human gastric cancer cell line,MGC80-3,was used .Expression of TR3 mRNA and its protein was detected by Northern blot and Western blot Localization of TR3 protein was showed by imunofluorescence analysis under laser-scanning confocal microscope.Apoptotic morthology was observed by DAPL fluorescence staining,and apoptotic index was couted manong 10000 cells randomly Stable transfection assay was carried out by Lipofectamine.RESULTS:Treatment of MGC80-3 cells with TPA and VP-16 resulted in apoptosis,accompanied by the repression of Bcl-2 protein in atime-dependent manner,At the same time,TPA and VP-16 also up-regulated expression level of TR3 mRNA in MGC80-3 cells that expressed TR3 mRNA When antisense-TR3 expression vector was transfected into the cells,expression of TR3 protein was repressed.In this case,TPA and VP-16 did not induce apoptosis.In addition,TPA and VP-16-induced apotosis involved in translocation of TR3,IN MGC80-3 cells,TR3 localized concentrative in nucleus,after treatment of cells with TPA and Vp-16,TR3 translocated from nuclesu to cytosol obviously,However,When this nuclear translocaion was blocked by LMB apoptosis was not occurred in MGC80-3 cells even in the presence of TPA and VP-16.CONCLUSION:Induction of apoptosis by TPA and VP-16 is through induction of TR3 expression and translocation of TR3 from nucleus to cytosol,Which may be a novel signal pathway for TR3,and represent the new biological function of TR3 to exert its effect on apoptosis in gastric cancer cells.     

不同体位干预对第三脑室肿瘤手术病人的影响

第三脑室的肿瘤手术一般需要采用枕部小脑幕入路，由于手术时间长．操作空间狭小，对手术体位的摆放要求甚高。既要充分暴露视野便于医生的手术操作．又要保护病人的神经、呼吸、循环等系统的重要生理功能，还要有利于麻醉师观察病人，避免病人神经、血管及各部位肌肉的损伤。     

Doxycycline attenuated pulmonary fibrosis induced by bleomycin in mice

The administration of doxycycline prior to bleomycin in mice attenuated pulmonary fibrosis. Bronchoalveolar neutrophil influx and gelatinase activity, but not caseinolytic activity, were attenuated by doxycycline. Established fibrosis was not affected by doxycycline. Thus, doxycycline might be useful for slowing down pulmonary fibrosis by biological activity other than antibacterial activity.     

Evaluation of the relationship between T663A polymorphism in the alpha-epithelial sodium channel gene and essential hypertension

Objectives:

To evaluate the relationship between alpha epithelial sodium channel (alpha-ENaC) T663A polymorphism and the risk of essential hypertension.

Methods:

This meta-analysis was conducted between November 2014 and February 2015 in Shanghai Medical Instrumentation College, Shanghai, China. We collected all published available case-control data (N=12) identified through PubMed, Web of Science, Scopus, and Chinese National Knowledge Infrastructure (CNKI) up to December 2014. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using the fixed- or random-effect model.

Results:

Although subgroup analysis showed that alpha-ENaC T663A polymorphism was associated with essential hypertension in North American individuals (OR=1.55, 95% CI=1.22-1.98, p=0.0003), our meta-analysis results did not confirm such association overall (OR=1.03, 95% CI=0.92-1.15, p=0.62). The lack of association was further confirmed by the non-superiority test (p<0.0001).

Conclusion:

Alpha-ENaC T663A polymorphism might not be a risk factor for essential hypertension.Hypertension is one of the most important risk factor for cardiovascular disease.1-3 However, its etiology in the vast majority of cases (~90%) is unknown, and thus the essential hypertension term is employed to describe such situations.4 Nowadays, essential hypertension is considered as a multifactorial disease resulting from the interplay of many genetic, environmental, and behavioral factors.5 Among them, sodium has long been deemed as one of the pivotal environmental factors due to its direct regulatory effect on blood pressure.5,6 The amiloride-sensitive epithelial sodium channel (ENaC) lies in the collecting duct of the kidney, and regulates sodium reabsorption. This channel is composed of 3 homologous subunits: alpha, beta, and gamma. Several studies have reported that mutations in beta-ENaC or gamma-ENaC can result in constitutive sodium reabsorption, thus leading to the development of an autosomal-dominant Mendelian hypertensive disorder, Liddle syndrome.7-11 Therefore, some “milder” mutations or functional polymorphisms were assumed to play some etiological roles in essential hypertension. Following this hypothesis, recent studies have reported some potential associated variants.12 Among them, T663A polymorphism in the alpha-ENaC gene has attracted some attention due to its reported ability to influence the channel activity.13,14 The A allele of T663A polymorphism could reduce the surface expression of ENaC, and the T allele of T663A polymorphism could increase ENaC activity.13,14 Accordingly, Ambrosius et al15 observed that the A allele of T663A polymorphism was associated with being normotensive in Blacks and Caucasians. However, a similar study performed in a Japanese population indicated that the A allele of T663A polymorphism was enriched in essential hypertensive patients,16 and Wang et al17 found that there was a lack of association between the T663A polymorphism and essential hypertension in 2 ethnic groups in China. Therefore, there is still a controversy over the association between T663A polymorphism in the alpha-ENaC gene and essential hypertension. Therefore, we performed a meta-analysis to investigate the relationship between alpha-ENaC T663A polymorphism and essential hypertension.     

Proteomic analysis of exosomes derived from human lymphoma cells

Background

Exosomes secreted by tumor cells contain specific antigens that may have immunotherapeutic purposes. The aim of this study was to characterize the proteomic content of lymphoma cell-derived exosomes (LCEXs).

Methods

In this study, exosomes derived from Raji cells (EXO_Raji) were purified and proteins of EXO_Raji were separated by one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Protein bands were identified by mass spectrometry. The protein components of EXO_Raji were analyzed using shotgun technology, and the function proteins of EXO_Raji were defined and described using the Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.

Results

A total of 197 proteins were identified in EXO_Raji; 139 proteins were also identified in Raji cells, showing an overlap of 70.56% of the total proteins in EXO_Raji. Interestingly, the remaining 58 proteins were unique to EXO_Raji. The GO database and KEGG were used to define and describe the function of proteins. The data showed that some important proteins involved in antigen procession and presentation as well as cell migration and adhesion were also identified in EXO_Raji, such as MHC-I and II, HSC70, HSP90, and ICMA-1.

Conclusions

LCEXs express a discrete set of proteins involved in antigen presentation and cell migration and adhesion, suggesting that LCEXs play an important role in the regulation of immunity and interaction between lymphoma cells and their microenvironment. LCEXs harbor most of the proteins of lymphoma cells and could be one of the sources of lymphoma-associated antigens for immunotherapeutic purposes.     

Coronal Diffusion-weighted Magnetic Resonance Imaging of the Kidney: Agreement with Axial Diffusion-weighted Magnetic Imaging in Terms of Apparent Diffusion Coefficient Values

Background:

Coronal diffusion-weighted magnetic resonance imaging (DW-MRI) and apparent diffusion coefficient (ADC) values have gradually become applied (following conventional axial DW-MRI) in the renal analysis. To explore whether data obtained using coronal DW-MRI are comparable with those derived using axial DW-MRI, this preliminary study sought to assess the agreement in renal ADC values between coronal DW-MRI and axial DW-MRI.

Methods:

Thirty-four healthy volunteers were enrolled in the study; written consents were obtained. All subjects underwent respiratory-triggered axial and coronal DW-MRI using a 1.5-MR system with b values of 0 and 800 s/mm². The signal-to-noise ratios (SNRs) of the two DW-MRI sequences were measured and statistically compared using the paired t-test. The extent of agreement of ADC values of the upper pole, mid-pole, and lower pole of the kidney; the mean ADC values of the left kidney and right kidney; and the mean ADC values of the bilateral kidneys were evaluated via calculation of intraclass correlation coefficients (ICCs) or Bland–Altman method between the two DW-MRI sequences.

Results:

The SNR of coronal DW-MR images was statistically inferior to that of axial DW-MR images (P < 0.001). The ICCs of the ADC values of each region of interest, and the mean ADC values of bilateral kidneys, between the two sequences, were greater than 0.5, and the mean ADCs of the bilateral kidneys demonstrated the highest ICC (0.869; 95% confidence interval: 0.739–0.935). In addition, 94.1% (32/34), 94.1% (32/34), and 97.1% (31/34) of the ADC bias was inside the limits of agreement in terms of the mean ADC values of the left kidneys, right kidneys, and bilateral kidneys when coronal and axial DWI-MRI were compared.

Conclusions:

ADC values derived using coronal DW-MRI exhibited moderate-to-good agreement to those of axial DW-MRI, rendering the former an additional useful DW-MRI method, and causing the ADC values derived using the two types of DW-MRI to be comparable.     

Structure-Based Design of GNE-495, a Potent and Selective MAP4K4 Inhibitor with Efficacy in Retinal Angiogenesis

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Anti-inflammatory effects of hinokitiol on human corneal epithelial cells: an in vitro study

Purpose

This study assessed the anti-inflammatory effect and mechanism of action of hinokitiol in human corneal epithelial (HCE) cells.

Methods

HCE cells were incubated with different concentrations of hinokitiol or dimethylsulfoxide (DMSO), which served as a vehicle control. Cell viability was evaluated using Cell Counting Kit-8 (CCK-8) assay. After polyriboinosinic:polyribocytidylic acid (poly(I:C)) stimulus, cells with or without hinokitiol were evaluated for the mRNA and protein levels of interleukin-8 (IL-8), interleukin-6 (IL-6), and interleukin-1β (IL-1β) using real-time PCR analysis and an enzyme-linked immunosorbent assay (ELISA), respectively. Nuclear and cytoplasmic levels of nuclear factor kappa B (NF-κB) p65 protein and an inhibitor of NF-κB α (IκBα) were evaluated using western blotting.

Results

There were no significant differences among the treatment concentrations of hinokitiol compared with cells incubated in medium only. Incubating with 100 μM hinokitiol significantly decreased the mRNA levels of IL-8 to 58.77±10.41% (P<0.01), IL-6 to 64.64±12.71% (P<0.01), and IL-1β to 54.19±8.10% (P<0.01) compared with cells stimulated with poly(I:C) alone. The protein levels of IL-8, IL-6, and IL-1β had similar trend. Further analysis revealed that hinokitiol maintained the levels of IκBα and significantly reduced NF-κB p65 subunit translocation to the nucleus which significantly inhibiting the activation of the NF-κB signal pathway.

Conclusion

Hinokitiol showed a significant protective effect against ocular surface inflammation through inhibiting the NF-κB pathway, which may indicate the possibility to relieve the ocular surface inflammation of dry eye syndrome (DES).