VEGF121 como Mediador de Efeitos Cardioprotetores Pós-Hipóxia via CaSR e via da Protease Dependente de Mitocôndria / VEGF121 Mediates Post-Hypoxia Cardioprotective Effects Via CaSR and Mitochondria-Dependent Protease Pathway

Resumo Fundamento: A doença cardiovascular é a principal causa de morte em todo o mundo. A apoptose mediada por hipóxia em cardiomiócitos é uma das principais causas de distúrbios cardiovasculares. O tratamento com a proteína do fator de crescimento endotelial vascular (VEGF, do inglês vascular endothelial growth factor) foi testado, mas as dificuldades operacionais limitaram seu uso. Entretanto, com os avanços da terapia gênica, aumentou o interesse na terapia gênica baseada no VEGF em doenças cardiovasculares. No entanto, o mecanismo preciso pelo qual a reposição de VEGF resgata os danos pós-hipóxia em cardiomiócitos não é conhecido. Objetivos: Investigar o efeito da expressão de VEGF121 pós-hipóxia utilizando cardiomiócitos de ratos neonatos. Métodos: Cardiomiócitos isolados de ratos neonatos foram utilizados para estabelecer um modelo in vitro de lesão cardíaca induzida por hipóxia. O efeito da superexpressão de VEGF, isolado ou em conjunto com inibidores de moléculas pequenas que têm como alvo os canais de cálcio, receptores sensíveis ao cálcio (CaSR, do inglês calcium-sensitive receptors) e calpaína, no crescimento e proliferação celular em lesão de cardiomiócitos induzidos por hipóxia, foram determinados com ensaio de MTT, coloração TUNEL, coloração com Anexina V/PI, lactato desidrogenase e atividade da caspase. Para análise estatística, um valor de p<0,05 foi considerado significativo. Resultados: Verificou-se que o efeito do VEGF121 foi mediado por CaSR e calpaína, mas não foi dependente dos canais de cálcio. Conclusões: Nossos resultados, mesmo em um ambiente in vitro, estabelecem as bases para uma validação futura e testes pré-clínicos da terapia gênica baseada em VEGF em doenças cardiovasculares.

Abstract Background: Cardiovascular disease is the major cause of death worldwide. Hypoxia-mediated apoptosis in cardiomyocytes is a major cause of cardiovascular disorders. Treatment with vascular endothelial growth factor (VEGF) protein has been tested but operational difficulties have limited its use. However, with the advancements of gene therapy, interest has risen in VEGF-based gene therapy in cardiovascular disorders. However, the precise mechanism by which VEGF replenishment rescues post-hypoxia damage in cardiomyocytes is not known. Objectives: To investigate the effect of post-hypoxia VEGF121 expression using neonatal rat cardiomyocytes. Methods: Cardiomyocytes isolated from neonatal rats were used to establish an in vitro model of hypoxia-induced cardiac injury. The effect of VEGF overexpression, alone or in combination with small-molecule inhibitors targeting calcium channel, calcium sensitive receptors (CaSR), and calpain on cell growth and proliferation on hypoxia-induced cardiomyocyte injury were determined using an MTT assay, TUNEL staining, Annexin V/PI staining, lactate dehydrogenase and caspase activity. For statistical analysis, a value of P<0.05 was considered to be significant. Results: The effect of VEGF121 was found to be mediated by CaSR and calpain but was not dependent on calcium channels. Conclusions: Our findings, even though using an in vitro setting, lay the foundation for future validation and pre-clinical testing of VEGF-based gene therapy in cardiovascular diseases.

Risk perception, emergency preparedness and emergency literacy among medical students under COVID-19 epidemic / 中国学校卫生

Objective@#To investigate risk perception, emergency preparedness and emergency literacy among medical students under COVID-19 epidemic.@*Methods@#An online survey was conducted by using the self designed COVID-19 questionnaire on risk perception, emergency preparedness and emergency literacy from March 27 to March 30, 2020. The convenience sampling method was used to investigate 4 864 medical students from 2 colleges and technical secondary schools in Sichuan Province.@*Results@#The scores of risk perception, emergency preparedness and emergency literacy associated with COVID-19 were(35.18±4.33)(28.30±4.16) and(25.23±2.97) respectively. Risk perception of medical students was positively correlated with emergency preparedness and emergency literacy(r=0.35, 0.40), emergency preparedness was positively correlated with emergency literacy(r=0.51)(P<0.05).@*Conclusion@#Considering interrelationships among risk perception, emergency preparedness and emergency literacy associated with COVID-19, medical students should be given targeted prevention and control training.

Ultrasound guidance improves the success rate of axillary plexus block: a meta-analysis / Orientação por ultrassom melhora a taxa de sucesso do bloqueio do plexo axilar: uma metanálise

ABSTRACT OBJECTIVE: To evaluate the value of real-time ultrasound (US) guidance for axillary brachial plexus block (AXB) through the success rate and the onset time. METHODS: The meta-analysis was carried out in the Anesthesiology Department of the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China. A literature search of Medline, EMBASE, Cochrane database from the years 2004 to 2014 was performed. The literature searches were carried out using medical subject headings and free-text word: "axilla", "axillary", "brachial plexus", "ultrasonography", "ultrasound", "ultrasonics". Two different reviewers carried out the search and evaluated studies independently. RESULTS: Seven randomized controlled trials, one cohort study and three retrospective studies were included. A total of 2042 patients were identified. 1157 patients underwent AXB using US guidance (US group) and the controlled group included 885 patients (246 patients using traditional approach (TRAD) and 639 patients using nerve stimulation (NS)). Our analysis showed that the success rate was higher in the US group compared to the controlled group (90.64% vs. 82.21%, p < 0.00001). The average time to perform the block and the onset of sensory time were shorter in the US group than the controlled group. CONCLUSION: The present study demonstrated that the real-time ultrasound guidance for axillary brachial plexus block improves the success rate and reduce the mean time to onset of anesthesia and the time of block performance.

RESUMO OBJETIVO: Avaliar o valor da orientação por ultrassonografia (US) em tempo real para bloqueio do plexo braquial por via axilar (BPBA) pela taxa de sucesso e tempo de latência. MÉTODOS: Uma metanálise foi feita no Departamento de Anestesiologia do Segundo Hospital Afiliado da Universidade de Soochow, Suzhou, província de Jiangsu, China. Fizemos uma pesquisa bibliográfica nas bases de dados Medline, Embasa e Cochrane de 2004 a 2014. A pesquisa foi feita com títulos de assuntos médicos e palavras de texto livre: axilla, axillary, brachial plexus, ultrasonography, ultrasound, ultrasonics. Dois revisores fizeram a pesquisa e avaliaram os estudos de forma independente. RESULTADOS: Sete estudos clínicos randômicos, um estudo de coorte e três estudos retrospectivos foram incluídos. Foram identificados 2.042 pacientes, dos quais 1.157 foram submetidos ao BPBA guiado por ultrassom (grupo US); o grupo controle incluiu 885 pacientes, dos quais 246 foram submetidos à abordagem tradicional (TRAD) e 639 à estimulação do nervo (EN). Nossa análise mostrou que a taxa de sucesso foi maior no grupo US em comparação com o grupo controle (90,64% vs. 82,21%, p< 0,00001). As médias do tempo necessário para fazer o bloqueio e do tempo de latência foram mais curtas no grupo US do que no grupo controle. CONCLUSÃO: O presente estudo demonstrou que a orientação por ultrassom em tempo real para o bloqueio do plexo braquial por via axilar melhora a taxa de sucesso e reduz a média do tempo de início da anestesia e do tempo de execução do bloqueio.

Endoplasmic reticulum stress and renal lesion in mice with combination of high-fat diet and streptozotocin-induced diabetes

ABSTRACT PURPOSE : To investigate in the kidney the pathologic changes and expression of GRP78 and CHOP in the Kunming (KM) mice with combination of high-fat diet and streptozotocin-induced diabetes. METHODS : Sixty two male KM mice were randomly divided into a normal control (NC) group (n=20) and a high-fat diet (HFD) group (n=42). After a four-week dietary manipulation, the KM mice in the HFD group were injected intraperitoneally with streptozotocin to induce diabetes. After diabetic models were successfully established, the kidneys were excised and conserved for further test. RESULTS : No significant difference in the body weight was observed after the dietary manipulation (p=0.554). After the streptozotocin was injected, fasting blood glucose levels in the diabetes group (DM) were significantly higher than that in the NC group (p＜0.0001). Glomerular atrophy observed under light microscope in the DM group was more serious compared with the NC group. The expression of GRP78 and CHOP in the kidneys of the mice in the DM group were higher compared with the NC group. CONCLUSION : Renal lesion occurs in the diabetic Kunming mice induced by combination of high-fat diet and low-dose streptozotocin, and endoplasmic reticulum stress and CHOP may contribute to the injury process.