lncRNA CDK5RAP3 regulates the proliferation and invasion of gastric cancer cells via miR-223-3p / 国际外科学杂志

Objective:To explore the expression of long non-coding RNA (lncRNA) CDK5RAP3 in gastric cancer tissue and its regulatory effect on gastric cancer cell proliferation and invasion.Methods:The expression differences of CDK5RAP3 in gastric cancer tissues and adjacent tissues were analyzed by TCGA database. By transfecting the pcDNA3.1-CDK5RAP3 plasmid into Hs-746T cells, a gastric cancer cell line overexpressing CDK5RAP3 (CDK5RAP3 group) was constructed, and the pcDNA3.1 plasmid was transfected into Hs-746T cells as a control group. The changes of CDK5RAP3 expression in the two groups of cells were detected by real-time quantitative PCR (qRT-PCR). The effects of overexpression of CDK5RAP3 on the proliferation and invasion of Hs-746T cells were detected by CCK-8 assay and Transwell assay, respectively. The binding sites of CDK5RAP3 and miR-223-3p were predicted by the starBase v2.0 database. The direct binding of CDK5RAP3 and miR-223-3p was verified by dual-luciferase reporter gene experiment. The expression levels of miR-223-3p in Hs-746T cells in each group were detected by qRT-PCR. Western blot was used to detect the expression levels of proliferation proteins and invasion proteins in Hs-746T cells in each group. The experimental data were analyzed by SPSS 17.0 software, and the measurement data conforming to the normal distribution were expressed as Mean±SD. The t-test was used to compare between two groups, and the one-way analysis of variance was used to compare the means of multiple groups. Results:Compared with adjacent tissues, the expression level of CDK5RAP3 in gastric cancer tissues was significantly lower ( P<0.01). The expressions of CDK5RAP3 in Hs-746T cells in the control group and CDK5RAP3 group were (1.08±0.77) and (10.63±2.14), respectively, and the difference was statistically significant ( P<0.01). Up-regulation of CDK5RAP3 significantly decreased the proliferation activity of Hs-746T cells ( P<0.05). The number of invasive cells in the control group and CDK5RAP3 group were (137.80±28.72) and (57.76±24.95), respectively, and the difference was statistically significant ( P<0.01). CDK5RAP3 could directly bind miR-223-3p ( P<0.01). The expression of miR-223-3p in Hs-746T cells in control group and CDK5RAP3 group were (6.22±1.20) and (1.01±0.98), respectively, and the difference was statistically significant ( P<0.01). Compared with the control group, up-regulation of CDK5RAP3 significantly reduced the expression levels of proliferation and invasive proteins. Conclusion:The expression of CDK5RAP3 is low in gastric cancer tissue, and CDK5RAP3 inhibits the proliferation and invasion of gastric cancer Hs-746T cells by targeting miR-223-3p.

Proteomics Analysis of Mechanism of Shenxiong Glucose Injection in Antagonizing H2O2-Induced Oxidative Damage in H9c2 Cells / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Shenxiong glucose injection （SGI） in inhibiting hydrogen peroxide （H2O2）-induced oxidative damage in H9c2 cells by tandem mass tags （TMT）-labeled quantitative proteomics. MethodH9c2 cells cultured in vitro were exposed to H2O2 for inducing oxidative damage. The cell viability was measured by cell proliferation and cytotoxicity assay （MTS）， followed by peptide fractionation by high performance liquid chromatography （HPLC） and protein expression detection in H9c2 cells by ultrahigh performance liquid chromatography-mass spectrometry. MaxQuant （v1.5.2.8） was utilized for data retrieval， and the high-resolution mass spectrometry was conducted to screen out differentially expressed proteins， which were then subjected to gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis. The protein expression levels of perilipin 2 （Plin2） and tropomyosin 1 （Tpm1） in cells were measured by Western blot. ResultThe spectral analysis yielded 48 608 specific peptide fragments and 5 903 quantifiable proteins. Compared with the model group，the SGI group exhibited 82 differentially expressed proteins，of which 22 were up-regulated and 60 were down-regulated. GO analysis results showed that the differentially expressed proteins were mainly involved in biological processes such as programmed cell death regulation，regulation of cell proliferation，cardiovascular system development， and cell migration. As revealed by KEGG analysis， these proteins were mainly related to peroxisome proliferator-activated receptor （PPAR），focal adhesion，phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt），and Ras-related protein 1 （Rap1） pathways. Western blot results demonstrated that compared with the model group，SGI significantly increased the Plin2 protein expression and decreased the Tpm1 protein expression （P<0.01），consistent with the proteomics results. ConclusionSGI may inhibit cell apoptosis and antagonize H2O2-induced cell oxidative damage by regulating PPAR，focal adhesion，PI3K/Akt and Rap1 pathways，which should be further verified by subsequent experiments.

Mediação artística e saúde coletiva: uma análise psicossocial da experiência de jovens rappers brasileiros e franceses / Artistic mediation and public health: a psychosocial analysis of the experience of young Brazilian and French rappers

Resumo O presente artigo discute os resultados de uma pesquisa-intervenção fundamentada na abordagem psicossocial clínica realizada junto a jovens rappers brasileiros e franceses, entre 13 e 27 anos. Nosso objetivo é analisar a função do rap, como mediação artística, para os jovens moradores de espaços urbanos desfavorecidos. A pesquisa de campo foi realizada a partir de observação participante e entrevistas nos dois países, entre outubro de 2007 e junho de 2009. Nossas análises mostram que o rap é utilizado pelos jovens para pensar sobre o mundo que os rodeia e para agir sobre as representações e o imaginário social negativos aos quais são associados, buscando o reconhecimento de um lugar positivo na sociedade. Através desta expressão artística podem realizar novas experiências sociais e subjetivas na cena social. O rap é também um suporte para constituição de grupos de pares e para construção de laços sociais entre jovens moradores de diferentes periferias do globo. Buscamos, assim, contribuir para discussão em torno da dimensão coletiva e singular de práticas de saúde, constitutivas de uma clínica que não se limita à procedimentos técnicos padronizados ou aos conhecimentos científicos de base biológica.

Abstract This article discusses the results of research-intervention based on the clinical psychosocial approach conducted among young Brazilian and French rappers between 13 and 27 years of age. Our objective is to analyze the function of rap, as artistic mediation, for the young inhabitants of disadvantaged urban areas. The field research was performed on the basis of participant observation and interviews in both countries. Our analyses show that rap is used by youths to reflect upon the world around them and to react to the negative representations and social imagery with which they are associated, seeking recognition of a positive place in society. Through this artistic expression they become able to accomplish new social and subjective experiences on the social scene. Rap is also a support for the formation of peer groups and social bonds among young inhabitants of different suburbs of the world. In this way, this study seeks to contribute to the discussion surrounding the collective and singular dimension of health practices, thereby constituting a research clinic that does not limit itself to standard technical procedures or to biologically-based scientific knowledge.

Nas batidas do rap: uma reflexão winnicottiana sobre o amadurecimento juvenil / Through the beating of rap music: a winnicottian reflexion about the youth maturing

Resumo: O estudo busca articular os possíveis sentidos expressos em letras de rap do cenário paulistano e o processo de amadurecimento emocional juvenil, a partir da teoria psicanalítica de D. W. Winnicott. Os trechos musicais selecionados foram alocados em três categorias de análise: a) Rap e os processos integrativos; b) Rap e a socialização juvenil; e c) A criatividade no rap. Verificou-se que as letras retratam o rap como instrumento facilitador ao uso de recursos psíquicos, a fim de colocar as angústias sob domínio egoico, conduzindo o indivíduo a uma posição transformadora de si, contribuindo para o amadurecimento e saúde emocional.

Abstract: The article seeks to articulate the possible meanings expressed in rap of the São Paulo scenario and the process of emotional maturation of the young, based on D. Winnicott's psychoanalytic theory. The sections are seen in three categories of analysis: a) Rap and the integrative processes; b) Rap and youth socialization; and c) Creativity without rap. It was found that the lyrics portray rap as an instrument which facilitates the use of psychic resources, in order to place the behavior on the egoic, leading the individual into a transforming position of self, contributing to maturity and emotional health.

Expressões de resiliência oculta nas letras do grupo de rap Facção Central / Expressions of hidden resilience in the lyrics of rap music group call "facção central" / Expresiones de resistencia oculta en las letras del grupo de rap Facção Central

Este artigo tem como objetivo analisar o conceito de resiliência oculta expresso nas letras de músicas do gênero rap. O estudo se configura como de natureza qualitativa, exploratório-descritivo, a partir da pesquisa documental. A pesquisa utilizou a musicografia do grupo de rap "Facção Central". No total, foram analisadas 125 músicas, sendo que 12 delas faziam menção direta a aspectos relacionados à resiliência oculta. A partir do material analisado, foram elaboradas 3 categorias: 1) Recursos materiais obtidos no crime; 2) Identidade e sensação de poder; 3) Relacionamentos afetivo-sexual. Os resultados apontam que, mesmo com os possíveis danos, pessoais e sociais, as atividades ilícitas, em especial o tráfico de drogas, podem trazer sentidos pessoais positivos às pessoas, sobretudo adolescentes e jovens de camadas sociais desfavorecidas. Os achados deste estudo reiteram as hipóteses sobre o conceito de resiliência oculta e convida pesquisadores a investirem neste campo temático.

This article aims to analyze the concept of hidden resilience expressed in the lyrics of rap songs. The study is configured as qualitative, exploratory-descriptive, based on documentary research. The research used the musicography of the rap group "Facção Central". In total, 125 songs were analyzed, 12 of which made direct mention of aspects related to hidden resilience. From the analyzed material, 3 categories were elaborated: 1) Material resources obtained in the crime; 2) Identity and feeling of power; 3) Affective-sexual relationships. The results show that even with the possible personal and social damage, illicit activities especially drug trafficking can bring positive personal meanings to people mainly adolescents and young people from disadvantaged social strata. The findings of this study reiterate the hypotheses about the concept of hidden resilience and invite researchers to invest in this thematic field.

Este artículo tiene como objetivo analizar el concepto de resistencia oculta expresado en las letras de las canciones de rap. El estudio está configurado como cualitativo, exploratorio-descriptivo, basado en la investigación documental. La investigación utilizó la musicografía del grupo de rap "Facção Central". En total, se analizaron 125 canciones, 12 de las cuales mencionaron directamente aspectos relacionados con la resistencia oculta. A partir del material analizado, se elaboraron 3 categorías: 1) Recursos materiales obtenidos en el delito; 2) Identidad y sentimiento de poder; 3) Relaciones afectivo-sexuales. Los resultados muestran que, incluso con el posible daño, las actividades ilícitas personales y sociales, especialmente el tráfico de drogas, pueden traer significados personales positivos a las personas, especialmente a los adolescentes y jóvenes de estratos sociales desfavorecidos. Los resultados de este estudio reiteran las hipótesis sobre el concepto de resiliencia oculta e invitan a los investigadores a invertir en este campo temático.

Pathogenic role leukotriene B4 in lung injury induced by lung-protective mechanical ventilation in rabbits / 南方医科大学学报

OBJECTIVE@#To elucidate the pathogenic role of leukotriene B4 (LTB4) in pulmonary hyper-permeability and inflammation induced by lung-protective mechanical ventilation (LPMV) in rabbits.@*METHODS@#Thirty-two healthy Japanese white rabbits were randomized into 4 groups for treatment with vehicle or bestatin (a leukotriene A4 hydrolase inhibitor that inhibits LTB4 production) administered intragastrically at the daily dose of 8 mg/kg for 5 days, followed by sham operation (group S and group BS, respectively, in which the rabbits were anesthetized only) or LPMV (group PM and group BPM, respectively, in which the rabbits received ventilation with 50% oxygen at a tidal volume of 8 mL/kg for 5 h). The concentrations of LTB4 and cyclic adenosine monophosphate (cAMP) in the lung tissues were analyzed by ELISA. cAMP content, protein kinase A (PKA) protein expression and the Rap1-GTP protein to total Rap1 protein ratio were determined to assess the activities of cAMP/PKA and Rap1 signaling pathways. The lung injury was evaluated by assessing lung permeability index, lung wet/dry weight ratio, polymorphonuclear leukocyte (PMN) count in bronchoalveolar lavage fluid (BALF), pulmonary myeloperoxidase (MPO) activity and lung histological scores.@*RESULTS@#None of the examined parameters differed significantly between group S and group BS. All the parameters with the exception of lung histological score increased significantly in group PM and group BPM as compared to those in group S (@*CONCLUSIONS@#LPMV can induce LTB4 overproduction to down-regulate cAMP/PKA and Rap1 signaling pathways in the lungs of rabbits, which results in lung hyper-permeability and inflammation. Bestatin can inhibit LTB4 production in the lungs to protect against LPMV-induced lung hyper-permeability and inflammation.

Ginsenoside Rd inhibits IL-1ß-induced inflammation and degradation of intervertebral disc chondrocytes by increasing IL1RAP ubiquitination

Many compounds of ginsenosides show anti-inflammatory properties. However, their anti-inflammatory effects in intervertebral chondrocytes in the presence of inflammatory factors have never been shown. Increased levels of pro-inflammatory cytokines are generally associated with the degradation and death of chondrocytes; therefore, finding an effective and nontoxic substance that attenuates the inflammation is worthwhile. In this study, chondrocytes were isolated from the nucleus pulposus tissues, and the cells were treated with ginsenoside compounds and IL-1β, alone and in combination. Cell viability and death rate were assessed by CCK-8 and flow cytometry methods, respectively. PCR, western blot, and immunoprecipitation assays were performed to determine the mRNA and protein expression, and the interactions between proteins, respectively. Monomeric component of ginsenoside Rd had no toxicity at the tested range of concentrations. Furthermore, Rd suppressed the inflammatory response of chondrocytes to interleukin (IL)-1β by suppressing the increase in IL-1β, tumor necrosis factor (TNF)-α, IL-6, COX-2, and inducible nitric oxide synthase (iNOS) expression, and retarding IL-1β-induced degradation of chondrocytes by improving cell proliferation characteristics and expression of aggrecan and COL2A1. These protective effects of Rd were associated with ubiquitination of IL-1 receptor accessory protein (IL1RAP), blocking the stimulation of IL-1β to NF-κB. Bioinformatics analysis showed that NEDD4, CBL, CBLB, CBLC, and ITCH most likely target IL1RAP. Rd increased intracellular ITCH level and the amount of ITCH attaching to IL1RAP. Thus, IL1RAP ubiquitination promoted by Rd is likely to occur by up-regulation of ITCH. In summary, Rd inhibited IL-1β-induced inflammation and degradation of intervertebral disc chondrocytes by increasing IL1RAP ubiquitination.

Hedyotis diffusa Willd selectively promotes mesenchymal-epithelial transition of human renal cancer ACHN cells by inhibiting RAP1-JNK signaling pathway / 肿瘤

Objective: To investigate the effects of Hedyotis diffusa Willd (HDW) on the proliferation, cell cycle, apoptosis, migration and invasion of human renal carcinoma cells, and to explore the possible mechanisms. Methods: After human renal adenocarcinoma ACHN cells and human renal proximal tubule HK-2 cells were treated with HDW for 24 h, the cell proliferation was detected by CCK-8 assay, and the cell cycle and apoptosis were detected by FCM assay. The phenotypes of ACHN and HK-2 cells treated with HDW were observed by light microscopy and rhodamine staining. The expressions of mesenchymal-epithelial transition (MET)-related proteins were detected by immunofluorescence staining and Western blotting, respectively. The effects of HDW on the migration and invasion of ACHN and HK-2 cells were detected by wound-healing and Transwell chamber assay. RNAsequencing was used to detect the effect of HDW on the transcriptome in ACHN cells. The expression levels of RAP1 pathway-related genes [RAP1 GTPase activating protein (RAP1GAP), RAS guanyl releasing protein 2 (RASGRP2), RAP guanine nucleotide exchange factor 3 (RAPGEF3), membrane-associated guanylate kinase, WW and PDZ domain containing 1 (MAGI1) and G protein subunit alpha i1 (GNAI1)] were detected by real-time fluorescent quantitative PCR. The expression levels of mitogen-activate protein kinase (MAPK) pathway-related proteins [c-Jun N -terminal kinase (JNK), phospho-JNK (p-JNK), protein kinase B (PKB, Akt), phospho-Akt (p-Akt), extracellular signalregulated kinase (ERK) and phospho-ERK (p-ERK)] were detected by Western blotting. Results: HDW selectively inhibited the proliferation of ACHN cells (P < 0.01), blocked cell cycle at S-phase (P < 0.01), and induced apoptosis (P < 0.01). After treatment with HDW, the morphology of ACHN cells significantly changed. HDW promoted the expressions of MET-related proteins (E-cadherin 1 and β-catenin) in ACHN cells, and inhibited the expressions of epithelial-mesenchymal transition (EMT)-related proteins (Vimentin and Snail1) (all P < 0.01). HDW inhibited the migration and invasion of ACHN and HK-2 cells (all P < 0.01), and there was no significant difference between ACHN and HK-2 cells. HDW affected the expressions of cell cycle-related genes and transcription factor E2F and Myc target genes, and activated the p53 signaling pathway. HDW significantly downregulated the expression levels of RAP1GAP, RASGRP2, RAPGEF3, MAGI1 and GNAI1 (all P < 0.000 1) and the phosphorylation level of JNK in ACHN cells. Conclusion: HDW may selectively inhibit cell proliferation, and promote MET, cell cycle arrest and apoptosis of ACHN cells by inhibiting RAP1-JNK signaling pathway.

Telomere-dependent and telomere-independent roles of RAP1 in regulating human stem cell homeostasis

RAP1 is a well-known telomere-binding protein, but its functions in human stem cells have remained unclear. Here we generated RAP1-deficient human embryonic stem cells (hESCs) by using CRISPR/Cas9 technique and obtained RAP1-deficient human mesenchymal stem cells (hMSCs) and neural stem cells (hNSCs) via directed differentiation. In both hMSCs and hNSCs, RAP1 not only negatively regulated telomere length but also acted as a transcriptional regulator of RELN by tuning the methylation status of its gene promoter. RAP1 deficiency enhanced self-renewal and delayed senescence in hMSCs, but not in hNSCs, suggesting complicated lineage-specific effects of RAP1 in adult stem cells. Altogether, these results demonstrate for the first time that RAP1 plays both telomeric and nontelomeric roles in regulating human stem cell homeostasis.

Advances of role of Epac in fibrotic diseases / 中国药理学通报

Epac, an exchange protein directly activated by cAMP, is a newly discovered guanine nucleotide exchange factor. Epac is a key factor involved in a series of cAMP mediated signaling pathways. Fibrosis disease, a common disease in clinic, usually results from excessive deposition of extracellular matrix under the stimulation of normal physiology (such as aging) or different pathogenetic factors. Epac has been reported to play an important role in fibrotic diseases, so this paper reviews this role of Epac in order to promote the research and development of Epac related mechanisms and drugs.

A escuta psicanalítica de adolescentes em conflito com a lei: que ética pode sustentar esta intervenção? / The psychoanalytic listening of adolescents in conflict with the law: what kind of ethic can sustain this intervention? / Écoute psychanalytique des adolescents en conflit avec la loi: quelle éthique peut soutenir cette intervention?

O presente estudo partiu de uma pesquisa-extensão com jovens que se encontram em regime de Internação Provisória (IP), suspeitos de terem cometido atos considerados infracionais. Através do dispositivo que temos chamado de Rodas de R.A.P., oferecemos um espaço de fala e de escuta a esse grupo de adolescentes que aguardava, em uma Instituição Socioeducativa, a deliberação de uma sentença - uma medida socioeducativa de meio aberto, de restrição ou de privação de liberdade - ou mesmo de seu desligamento. Escolhemos a denominada IP por esta ser a porta de entrada da Instituição e por considerarmos esse momento inicial como um tempo de muita angústia, quando se faz necessária uma escuta mais atenta aos meninos que se envolvem em situações de conflito com a lei. Nessa experiência, ao debruçarmo-nos sobre o tema da ética passível de sustentar a intervenção do pesquisador-psicanalista na socioeducação, pretendemos problematizar a discussão metodológica acerca da construção de dispositivos de escuta no âmbito das Políticas Públicas infanto-juvenis, especialmente no que se refere às políticas de socioeducação.

The present study was based on a research-extension with adolescents who are in a Provisional Internment (IP) regime, suspected of having committed acts considered to be against the law. Trough the device we have named R.A.P. Circles, we offer a space for talking and listening to this group of adolescents who were waiting in a socioeducation institution for a sentence - socioeducational measure of open way, of restriction or deprivation of liberty - or even of its termination. We chose the so-called IP for this to be the institution's kind of input door and because we consider this initial moment as a time of great distress, when it becomes necessary to listen more attentively to the adolescents who are involved in situations of conflict with the law. In this experience, as we look at the ethical issue that can sustain the intervention of the psychoanalyst-researcher in the socioeducation system, we intend to problematize a methodological discussion about the construction of listening devices within the framework of the Public Policies for children and youth, especially with regard to socio-educational policies.

La présente étude a été basée sur un projet de recherche et extension avec des jeunes qui sont dans un régime d'internat provisoire (IP), soupçonnés d'avoir commis des actes considérés des infractions. À travers l'outil, que nous convenons d'appeler RAP, nous offrons un espace pour faire parler et faire écouter ce groupe d'adolescents qui attendent dans une institution socio-éducative une décision juridique - une mesure socio-éducative de moyens ouverts, de restriction ou de privation de liberté - ou même de son retrait. Nous avons choisi la condition IP parce qu'elle est la porte d'entrée de l'institution et parce que nous considérons ce moment initial une période de grande angoisse, moment où il faut faire écouter très attentivement les enfants impliqués dans des situations de conflit avec la loi. Dans cette expérience, lorsque nous examinons le choix de l'éthique qui peut soutenir l'intervention du psychanalyste-chercheur dans la socio-éducation, nous avons l'intention de problématiser la discussion méthodologique axée sur la construction d'appareils d'écoute dans le cadre des politiques publiques d'enfance et de jeunesse, notamment en ce qui concerne aux politiques socio-éducatives.

Periodontally Accelerated Osteogenic Orthodontics(Paoo): A Novel Rapid Approach

Wilckodontics, also known as Periodontally Accelerated Osteogenic Orthodontics (PAOO) is a relatively new treatment in the dental realm. It is a clinical procedure that combines selective alveolar corticotomy, particulate bone grafting and the application of orthodontic forces. Basically it is a combination of selective decortication facilitated orthodontic technique and alveolar augmentation. This procedure is theoretically based on the bone healing pattern known as the regional acceleratory phenomenon (RAP).2 Regional acceleratory phenomenon was developed by Frost and Jee in 19833,4. The decortication of bone results in an increased turnover of alveolar spongiosa with areas of alveolar demineralization. This results in osteopenia, where its mineral content temporarily decreased which enables teeth to be moved more rapidly and further through the collagenous soft tissue matrix of the bone . Following the completion of orthodontic treatment, remineralization takes place resulting in greater stability in the orthodontic treatment outcome. Dr. Thomas Wilcko (Periodontist) and William Wilcko (Orthodontist), of Erie, PA in 1995 further modified the corticotomy assisted orthodontic technique with the addition of alveolar augmentation and named the procedure as Periodontally Accelerated Osteogenic Orthodontics (PAOO) later patented as "Wilckodontics" based on the emerging concepts of Wilcko others. This procedure has been shown to be particularly effective in treating moderate to severe crowding, in Class II malocclusions requiring expansion or extractions, and mild Class III malocclusions. As long as healthy periodontium is present, PAOO can be done at any age (from 11 years to 77 years of age)

Expressions and clinical significance of GAS1, IL-1RAP and PRF1 in patients with ALK positive anaplastic large cell lymphoma / 中华血液学杂志

Objective@#To investigate the expressions of growth arrest-specific protein (GAS1), IL-1 receptor accessory protein (IL-1RAP) and perforin (PRF1) in patients with anaplastic lymphoma kinase positive, anaplastic large cell lymphoma (ALK+ ALCL) and their relationships with clinical significances and the prognoses of ALK+ ALCL.@*Methods@#Twenty-six formalin-fixed paraffin-embedded (FFPE) samples of ALK+ ALCL patients who were diagnosed from January 2011 to September 2016 were collected. Twelve FFPE samples of patients with ALK+ALCL, 13 FFPE samples of patients with peripheral T cell lymphoma (not otherwise specified) (PTCL-NOS) and 8 FFPE samples of patients with angioimmunoblastic T-cell lymphoma (AITL) were used as control groups. RQ-PCR and immunohisto-chemical staining were used to detect the mRNA and protein expressions of GAS1, IL-1RAP and PRF1. The clinical data were analyzed.@*Results@#①The expression levels of GAS1, IL-1RAP and PRF1 gene and protein in ALK+ ALCL group were higher than those of the control groups (P<0.05), but the expression levels had no statistically significant differences between the control groups (P>0.05). ②Patients with elevated lactate dehydrogenase (LDH) (0.77 vs 1.38, z=-3.292, P=0.001) or International prognostic index (IPI)≥3(0.62 vs 1.29, z=-2.495, P=0.013) had lower expression level of GAS1. Patients with stage Ⅲ/Ⅳ disease (0.89 vs 1.18, z=-2.212, P=0.027) or IPI≥3 (0.48 vs 1.13, z=-2.008, P=0.045) had lower expression level of PRF1. IL-1RAP expression level was not associated with clinical features. ③ALK+ ALCL patients in complete remission (CR) group had higher expression levels of GAS1 and PRF1 than patients in non-remission (NR) group (P values were 0.016 and 0.009). ④Kaplan-Meier survival analysis showed that patients with high expression levels of GAS1 and PRF1 had longer median overall survival and progression-free survival than patients with low expression levels of GAS1 and PRF1.@*Conclusion@#GAS1, IL-1RAP and PRF1 could be molecular markers for ALK+ ALCL patients. They have potential diagnostic value and can be used for differential diagnosis in some difficult cases. ALK+ ALCL patients with high expression levels of GAS1 or PRF1 have better curative effects and prognoses.

Expression of Rap1, guanosine triphosphate Rap1, vascular endothelial growth factor and β-catenin in experimental choroidal neovascularization / 中华眼底病杂志

Objective To observe the expression ofRapl,guanosine triphosphate-Rapl (GTP-Rapl),vascular endothelial growth factor (VEGF) and β-catenin in experimental choroidal neovascularization (CNV).Methods Forty-two brown Norwegian rats were randomly divided into a blank control group (7 rats) and a model group (35 rats).Both eyes were enrolled.The CNV model was established by holmium ion laser photocoagulation in the model group.At 3,7,14,21,and 28 days after photocoagulation,fluorescein fundus angiography (FFA) and choroidal vascular smear were performed to observe the degree of fluorescein leakage and CNV area in rats;Western blot and real-time quantitative polymerase chain reaction (RT-PCR) were used to detect the expression ofRap1,GTP-Rap1,VEGF,β-catenin and mRNA in CNV.Results The results of FFA examination showed that a large disc-shaped fluorescein leaked in the photo-condensation spot 14 days after photocoagulation.Laser confocal microscopy showed that compared with 7 days after photocoagulation,CNV area increased at 14,21,28 days after photocoagulation,and the difference were statistically significant (t=3.725,5.532,3.605;P＜0.05).Western blot showed that there was no significant difference in the relative expression of Rap1 protein in CNV at different time points after photocoagulation between the two groups (P=0.156).Compared with the blank control group,the relative expression of GTP-Rap1 protein was significantlydecreased,the relative expression of VEGF and β-catenin protein were significantly increased in the model group (P=0.000).The results of RT-PCR showed that there was no significant difference in the relative expression of Rap 1 mRNA at different time points after photocoagulation between the two groups (P=0.645),but there were significant difference in the relative expression of β-catenin mRNA (P=0.000).At 7,14,21 and 28 days after photocoagulation,there were significant difference in the relative expression of GTP-Rap 1 and VEGF mRNA between the two groups (P=0.000).Conclusions The expression of GTP-Rap1 in experimental CNV is significantly lower than that in normal rats.

Epac1/Rap1 signaling pathway is involved in the pathogenesis of myocardial ischemia/reperfusion injury in rats / 中国药理学与毒理学杂志

OBJECTIVE In this study we explored the role of Epac1-Rap1 pathway in the acute myocardial ischemia/reperfusion injury (MIRI) in vitro and in vivo. METHODS An acute myocardial ischemia/reperfusion injury model was established by the ligation of left anterior descending coronary. Myocardial architecture, fibers and apoptosis was evaluated by the Masson trichrome staining, Sirius red staining and TUNEL assay.H9c2 cells were subjected to hypoxia for 5 h followed by 1-h reoxygen-ation in vitro.Cell viability was measured by MTT assay and cellular injury was evaluated by measuring the release of lactate dehydrogenase (LDH). Western blot, real-time PCR and immunofluorescence were used to detect the expressions of Epac1 and relative downstream molecules.RESULTS Myocardial IR-induced cardiac apoptosis and accumulation of Epac1 and Rap1 in rat IR injury model.Direct Epac activation by 8-CPT(8-(4-chlorophenylthio)-2′-O-methyl-cAMP)exacerbated cardiomyocyte death and dysfunction following hypoxia-reoxygenation(H/R),selective activation of Epac in response to H/R was evident which enriched for cytosolic/membrane proteins and mRNA. Harmacological inhibitor of Epac (ESI-09)significantly ameliorated myocardial injury with the decline of Epac expression.Epac inhibitor and agonist studies also implicated the effect of Rap1, which is downstream of Epac in this pathway. The expression of Rap1 elevated when activated by Epac agonist and was blocked by Epac inhibitor. The same result was true for myocyte CaMK-II and intracellular calcium ions activation.Moreover,ESI-09 also increased ERK1/2 phosphorylation. CONCLUSION Our study reveal that Epac1/Rap1 signaling pathway is involved in the pathogenesis of myocardial I/R injury in rats,which provides evidence on the development of therapeutic strategies target this pathway for myocardial I/R injury.

Jovens "infratores", o RAP e o poetar: deslizamentos da "vida nua" à "vida loka" / Adolescents in conflict with the law, RAP and poetize: slips of "bare life" to "crazy life" / Jóvenes "infractores", el RAP y el poetar: deslizamientos de la "nuda vida" a la "vida loca" / Adolescents en conflit avec la loi, le RAP et la poésie: déplacements de la « vie nue¼ à la «vie folle¼

Este artigo apresenta o início de uma interlocução entre a Psicanálise e a socioeducação através da construção de uma Oficina de rap (Ritmos, Adolescência e Poesia) como dispositivo de pesquisaintervenção com adolescentes em conflito com a lei que se encontram em uma instituição de execução de medidas socioeducativas de privação de liberdade. Através do rap, buscamos extrair um pouco de "poesia" do cotidiano árido que compõe as vidas desses meninos. Ao escutar a dimensão do traumático da exclusão em suas narrativas, e contando com a potência da palavra e da música, buscamos um modo de evocar deslocamentos em algumas significações cristalizadas. O trabalho teve como sustentação teórico-metodológica a conjugação da psicanálise de Freud e Lacan articulada ao tema da experiência em Walter Benjamin. A partir da experiência nas Oficinas construímos algumas reflexões que ensejam o que temos proposto como diálogo da Psicanálise com a socioeducação. Nesse sentido, também ensaiamos uma reflexão acerca da posição desses sujeitos com o que Agamben conceitua sobre o "homo sacer" e a "vida nua". As letras de rap enunciam o sofrimento que esses jovens sentem pela dimensão de suas vidas como "mera vida". Como efeito do trabalho, entendemos o rap como um modo de poetar, que faz circular os significantes das vidas "ressacadas", com o que relativiza o peso do lugar da exclusão. Deste modo, o artigo mostra a potência de se considerar o rap como um dispositivo passível de oferecer a esses meninos condições para que possam deslizar da "vida nua", que lhes colocou na via do conflito com a lei, para tantas outras significações quanto a aventura com a polissemia da palavra e da música tenha condição de lhes propiciar.

This article presents the beginning of a dialogue between Psychoanalysis and socioeducation, through the construction of an RAP (Rhythm, Adolescence and Poetry) workshop as a listening-intervention device with adolescents in conflict with the law who are in a socio-educational institution. Through RAP, we seek to draw a little "poetry" of the arid everyday that characterizes the lives of these boys. Hearing the dimension of traumatic exclusion in their narratives, and with the power of words and music, we seek a way to evoke movements in chronicle meanings. The work has, as theoretical and methodological support, the combination of psychoanalysis of Freud and Lacan articulated the theme of experience in Walter Benjamin. From the experience in the workshops we built some reflections that show what we have proposed as a dialogue between psychoanalysis and socioeducation. We also rehearsed a reflection on the position of these subjects with what Agamben conceptualizes regarding the "homo sacer" and the "bare life". RAP's lyrics seem to enunciate the suffering they feel for the dimension of their lives as mere life. Therefore, RAP comes as a poetizing mode, circulating the signifiers of "ressacadas" lives and relativizing the weight of the position of exclusion. We believe that such developments may open the prospect that the bare life, which put them on the path of conflict with the law, slide to as many meanings as the adventure with the polysemy of words and music can provide them.

Este artículo presenta el inicio de una interlocución entre el Psicoanálisis y la socioeducación a través de la construcción de un taller de RAP (Ritmos, Adolescencia y Poesía) como un dispositivo de investigación-intervención con adolescentes en conflicto con la ley que se encuentran en una institución de aplicación de medidas socioeducativas de privación de libertad. A través del RAP, buscamos extraer un poco de "poesía" de la árida vida cotidiana que constituye la existencia de estos adolescentes. Al escuchar la dimensión del traumático de la exclusión en sus narrativas, y contando con el poder de la palabra y de la música, buscamos una manera de evocar desplazamientos en significaciones ya crónicas. El estudio tiene como soporte teórico-metodológco la combinación del psicoanálisis de Freud y Lacan articulado al tema de experiencia en Walter Benjamin. A partir de la experiencia en los Talleres construimos algunas reflexiones que enseñan lo que hemos propuesto como diálogo del psicoanálisis con la socioeducación. Además, ensayamos una reflexión sobre la posición de esos sujetos con lo que Agamben conceptualiza acerca del "homo sacer" y de la "nuda vida". Las letras del RAP parecen aseverar el dolor que sienten por la dimensión de sus vidas como "mera vida". Como efecto del trabajo, entendemos el RAP como un modo de poetar, que hace circular los significantes de las vidas "resacadas", con lo que relativiza el peso del lugar de la exclusión. De este modo, el artículo muestra la potencia de considerar el RAP como un dispositivo capaz de ofrecer a esos niños condiciones para que puedan deslizar de la "nuda vida", que les puso en la vía del conflicto con la ley, para tantas significaciones como la aventura con la polisemia de la palabra y de la música tenga la condición de propiciarlos.

Cet article présente le parcours de construction d'un atelier de RAP (Rythmes, Adolescence et Poésie) comme outil d'écoute-intervention auprès des adolescents en conflit avec la loi, lesquels sont dans un établissement d'application de mesures socio-éducatives de la privation de liberté. À travers le RAP, nous cherchons à obtenir un peu de «poésie¼ du quotidien aride qui fait partie de la vie de ces jeunes. En écoutant la dimension traumatique d'exclusion de leurs récits, et en se basant sur le pouvoir de la parole et de la musique, nous cherchons une façon d'évoquer quelques déplacements dans les significations chroniques. Le travail a comme approche théorique et méthodologique le carrefour de la psychanalyse chez Freud et Lacan articulée au thème de l'expérience chez Walter Benjamin. De l'expérience dans des ateliers construit quelques réflexions qui ensejam ce que nous avons proposé que le dialogue de la psychanalyse avec socioeducation. En ces sense, nous avons repéré une réflexion sur la position de ces sujets avec ce qu'Agamben conceptualise sur l' « homo sacer ¼ et la « vie nue ¼. Les paroles de RAP semblent énoncer la souffrance qu'ils ressentent à propos de la dimension de leur vie en tant que « simple vie ¼. L'effet du travail, nous comprenons le RAP comme mode de poétisation, en faisant circuler les signifiants de vies «ressacadas¼ ou déséchées et en apaisant le poids du lieu d'exclusion. Ainsi, l'article montre le pouvoir de considérer le RAP comme un dispositif capable d'offrir ces garçons conditions afin qu'ils puissent glisser la « vie nue ¼, ce qui les a mis sur la voie du conflit avec la loi, pour autant de significations que l'aventure avec la polysémie du mot et de la musique a la condition de leur fournir.

Freshwater mollusks and environmental assessment of Guandu River, Rio de Janeiro, Brazil / Moluscos de água doce e avaliação ambiental do rio Guandu, Rio de Janeiro, Brasil

Abstract The Guandu River Basin is extremely important to state of Rio de Janeiro, as a water supplier of several municipalities. However, the malacological knowledge and environmental status is not well known to this basin. The aim of this paper is to present an inventory of freshwater mollusks, as well as an environmental assessment through a Rapid Assessment Protocol, of ten sampling sites at Guandu River basin in six municipalities (Piraí, Paracambi, Japeri, Seropédica, Queimados and Nova Iguaçu). Thirteen species of molusks were found, eight native (Pomacea maculata, Biomphalaria tenagophila, Gundlachia ticaga, Gundlachia radiata, Omalonyx matheroni, Diplodon ellipticus, Anodontites trapesialis and Eupera bahiensis) and five exotics (Melanoides tuberculata, Ferrissia fragilis, Physa acuta, Corbicula fluminea and Corbicula largillierti). The environmental analysis ranked most sites as "modified". The expansion of exotic species with their associated negative effects, as well the gap in knowledge of native species calls attention to the need of future studies of biology and ecology of the species found.

Resumo A bacia do rio Guandu é de extrema importância para o estado do Rio de Janeiro, pois abastece grande parte da região metropolitana. Contudo, aspectos malacológicos e ambientais desta bacia são pouco conhecidos. O presente trabalho teve por objetivo realizar um inventário das espécies de moluscos de água doce ocorrentes na região, assim como uma avaliação ambiental através de um Protocolo de Avaliação Rápida, de dez estações de coleta na bacia do rio Guandu em seis municípios (Piraí, Paracambi, Japeri, Seropédica, Queimados e Nova Iguaçu). Foram encontradas 13 espécies, sendo oito nativas (Pomacea maculata, Biomphalaria tenagophila, Gundlachia ticaga, Gundlachia radiata, Omalonyx matheroni, Diplodon ellipticus, Anodontites trapesialis e Eupera bahiensis) e cinco exóticas (Melanoides tuberculata, Ferrissia fragilis, Physa acuta, Corbicula fluminea e Corbicula largillierti). A avaliação ambiental caracterizou a maior parte das estações de coleta como "modificado". A dispersão das espécies exóticas e os efeitos negativos a elas associados, além da nossa falta de conhecimento sobre as espécies nativas chama a atenção para a necessidade de futuros estudos biológicos e ecológicos das espécies encontradas.

Relationship between methylation status of Rap1 GTPase activating protein and colon cancer / 肿瘤研究与临床

Objective To explore the methylation status of Rap1 GTPase activating protein (Rap1GAP) promoter in colon cancer, and to provide the oretical basis and research direction for the early diagnosis, targeted therapy, anti-multidrug resistance of colon cancer and so on. Methods The paraffin embedded specimens of 33 patients with colonic adenocarcinoma diagnosed by pathology were analyzed from Department of Pathology of Xinzhou City People′s Hospital from January 2010 to September 2014, including 19 males and 14 females, and aged 41-72 years old. The paraffin embedded specimens of 16 patients with colonic adenoma were enrolled, including 9 males and 7 females, and aged 34-58 years old. 13 normal tissues from the tumor distal margin (from the tumor > 15 cm) were selected. Quantitative methylation specific PCR (q-MSP) was applied to detect methylation level of Rap1GAP gene promoter. The methylation level differences of Rap1GAP gene promoter region among 3 groups or between different clinicopathologic factor subgroups were compared. Results The methylation rates [median (interquartile range)] of Rap1GAP promoter were 65.43 % (50.35 %), 21.37 % (8.39 %) and 17.43 % (15.71 %) in colonic adenocarcinoma group, colonic adenoma group and adjacent normal tissue group, respectively. The methylation rate of colonic adenocarcinoma group was significantly higher than that of colon adenoma group or that of adjacent normal tissue group (P60yearsold:36.26%(62.62%)and26.23%(76.42 %);well-differentiated vs. moderately/poorly-differentiated: 21.98 % (40.32 %) vs. 42.74 % (74.20 %); TNM Ⅰ-Ⅱ vsⅢ-Ⅳ: 25.31 % (48.27 %) vs. 36.26 % (75.55 %); all P> 0.05]. Conclusion The methylation status of RAP1GAP promoter maybe associate with genesis and development of colon cancer, which might be used as a target for early diagnose of colon cancer.

The Introducion of Professor YE Jin's Experience in Treating Infantile Recurrent Abdominal Pain / 浙江中医药大学学报

[Objective]The paper was designed to introduce the Professor YE Jin's personal clinical experience which can provide an effective means for other pediatrician.[Method]By introducing the Professor YE Jin's personal clinical experience,we summarize the effective therapies about the infantile recurrent abdominal pain(RAP). [Result]According to the Professor YE Jin, the pathomechanism of RAP includes mainly cold stagnation, the indigestion, parasite and Qi stagnancy. RAP caused bycoldcan be treated from warming the middle-energizer and fending off the cold,RAP resulting from retention of food can be cured by removing the retention and invigorating the stomach, RAP incurred by ascaris can be cured by relieving ascariasis,expelling parasite and purgation simultaneously,and RAP resulting from Qi stagnation can be cured by soothing liver, regulating qi activity, rather than relieving pain merely. Based on the above-mentioned theory,she tends to use Liquorice and prefers Paeonia a lot in curing the disease, that is always effective in clinic as a result.The recurrence rate is also lower.One case was provided for verification.[Conclusion]Professor YE Jin thinks that warming the middle-energizer and fending off the cold, removing the retention and invigorating the stomach, the RAP can be improved the curative effect,and that can provide another idea for other clinicians.

Clinical and systemic effects of periodontally accelerated osteogenic orthodontics: a pilot study / Efectos clínicos y sistémicos de la ortodoncia osteogénica periodontalmente acelerada: un estudio piloto

The aim of this study was to describe periodontal effects and treatment time of Periodontally Accelerated Osteogenic Orthodontics (PAOO) and to determine if Deoxypyridinoline could be used as a biochemical marker of bone turnover in patients undergoing PAOO. We compared 5 patients undergoing PAOO (5 males, mean age: 29.6±9.8 years) with 5 control patients undergoing self-ligating orthodontics (5 males, mean age: 28.5±6.3 years). All patients were evaluated using panoramic and lateral x-rays and CBCT and randomly selected in experimental and control groups. Both groups underwent self-ligating orthodontics using Damon Q braces. Only the experimental group underwent PAOO. The patients were evaluated periodontally at T1 (before surgery and orthodontic movement) and T2 (after orthodontic treatment). The total treatment time for the experimental group was 8.2±3.3 months and for the control group was 13.4±7.3 months. There were no differences between T2-T1 periodontal variables in either of the groups. Gingival recession was 0.49±0.26 mm at T1 and 0.42±0.3 mm at T2 in the experimental group. Gingival recession was 0.55±0.31 mm at T1 and 1.19±0.24 mm at T2 in the control group. Deoxypyridinoline urine levels showed great variance between individuals and between groups. There is a reduction in treatment time for patients undergoing PAOO with DAMON Q braces. There is no difference in the periodontal condition between PAOO and conventional orthodontics.

El objetivo de este estudio fue describir los efectos periodontales y el tiempo de tratamiento de ortodoncia osteogénica periodontalmente acelerada (OOPA) y para determinar si desoxipiridinolina podría ser utilizado como un marcador bioquímico de recambio óseo en pacientes sometidos a OOPA. Se estudiaron 5 pacientes sometidos a OOPA (hombres, edad media de 29,6±9,8 años) y 5 pacientes control sometidos a ortodoncia de autoligado (hombres, edad media de 28,5±6,3 años). Todos los pacientes fueron evaluados utilizando radiografías panorámicas y laterales, tomografía computadorizada de haz cónico, y luego distribuidos aleatoriamente en grupos experimentales y de control. Ambos grupos fueron sometidos a la ortodoncia de autoligado utilizando dispositivos ortodónticos Damon Q. Sólo el grupo experimental fue sometido a OOPA. Los pacientes fueron evaluados periodontalmente en T1 (antes de la cirugía y el movimiento de ortodoncia) y T2 (después de un tratamiento de ortodoncia). El tiempo total de tratamiento para el grupo experimental fue de 8,2±3,3 meses y para el grupo control 13,4±7,3 meses. No hubo diferencias entre las variables periodontales T2-T1 en cualquiera de los grupos. La recesión gingival en el grupo experimental fue de 0,49±0,26 mm en T1 y 0,42±0,3 mm en T2. En el grupo control, la recesión gingival fue 0,55±0,31 mm en T1 y 1,19±0,24 mm en T2. Los niveles de desoxipiridinolina en orina mostraron gran variación entre individuos y entre grupos. Hubo una reducción en el tiempo de tratamiento para los pacientes sometidos OOPA con dispositivos ortodónticos Damon Q. No hubo diferencia en la condición periodontal entre pacientes sometidos a OOPA y ortodoncia convencional.