Current research status on immune-related adverse events / 中华胃肠外科杂志

Immune checkpoint inhibitors have progressed rapidly over the past decade and have become one of the most promising oncology treatments. However, immune checkpoint inhibitors reduce T-cell tolerance and lead to a unique spectrum of immune-related adverse events (IRAE). IRAE can involve multiple systems, including endocrine, gastrointestinal, respiratory and skin systems and there is no predictive marker with high specificity and sensitivity. Mild IRAE can be alleviated by discontinuing immune checkpoint inhibitors while severe IRAEs require active intervention. The first-line treatment is glucocorticoids, and immunosuppressants can be considered in refractory cases. However the optimal choice of immunosuppressants is currently controversial. This review provides an overview of the epidemiology and possible mechanisms of immune-related adverse events, outlines some promising predictive biomarkers, and describes several immunotherapy-related organ toxicity and management.

Aquaporin 9 in rat brain after severe traumatic brain injury / Aquaporina 9 em cérebro de rato após traumatismo cerebral grave

OBJECTIVE: To reveal the expression and possible roles of aquaporin 9 (AQP9) in rat brain, after severe traumatic brain injury (TBI). METHODS: Brain water content (BWC), tetrazolium chloride staining, Evans blue staining, immunohistochemistry (IHC), immunofluorescence (IF), western blot, and real-time polymerase chain reaction were used. RESULTS: The BWC reached the first and second (highest) peaks at 6 and 72 hours, and the blood brain barrier (BBB) was severely destroyed at six hours after the TBI. The worst brain ischemia occurred at 72 hours after TBI. Widespread AQP9-positive astrocytes and neurons in the hypothalamus were detected by means of IHC and IF after TBI. The abundance of AQP9 and its mRNA increased after TBI and reached two peaks at 6 and 72 hours, respectively, after TBI. CONCLUSIONS: Increased AQP9 might contribute to clearance of excess water and lactate in the early stage of TBI. Widespread AQP9-positive astrocytes might help lactate move into neurons and result in cellular brain edema in the later stage of TBI. AQP9-positive neurons suggest that AQP9 plays a role in energy balance after TBI.

OBJETIVO: Revelar a expressão e os possíveis papéis da aquaporina 9 (AQP9) no cérebro de ratos após lesão cerebral traumática (LCT) grave. MÉTODOS: Foram utilizados: determinação do conteúdo cerebral de água, corante cloreto de tetrazólio, corante azul de Evans, imunoistoquímica (IHQ), imunofluorescência (IF), western blot e PCR em tempo real. RESULTADOS: O conteúdo cerebral de água alcançou o primeiro e o segundo (o mais alto) picos após 6 e 72 horas. A função da barreira hematoencefálica se mostrou muito prejudicada após 6 horas da LCT. A pior isquemia cerebral ocorreu após 72 horas da LCT. Astrócitos AQP9 positivos e neurônios no hipotálamo foram detectados difusamente pela IHQ e IF após LCT. A abundância de AQP9 e de sua mRNA aumentou após LCT e alcançou dois picos após 6 e 72 horas, respectivamente, da LCT. CONCLUSÕES: AQP9 aumentada pode contribuir para a eliminação de água e lactato em excesso na fase precoce da LCT. Astrócitos difusamente localizados AQP9 positivos podem ajudar a entrada do lactato nos neurônios, promovendo edema cerebral celular na fase tardia da LCT. Neurônios AQP9 positivos sugerem que AQP9 tem um papel no equilíbrio energético após LCT.