Oxidative stress induced necroptosis activation is involved in the pathogenesis of hyperoxic acute lung injury.

Necroptosis has been found to be involved in the pathogenesis of some lung diseases, but its role in hyperoxic acute lung injury (HALI) is still unclear. This study aimed to investigate contribution of necroptosis to the pathogenesis of HALI induced by hyperbaric hyperoxia exposure in a rat model. Rats were divided into control group, HALI group, Nec-1 (necroptosis inhibitor) group and edaravone group. Rats were exposed to pure oxygen at 250 kPa for 6 h to induce HALI. At 30 min before hyperoxia exposure, rats were intraperitoneally injected with Nec-1 or edaravone, and sacrificed at 24 h after hyperoxia exposure. Lung injury was evaluated by histology, lung water to dry ratio (W/D) and bronchoalveolar lavage fluid (BALF) biochemistry; the serum and plasma oxidative stress, expression of RIP1, RIP3 and MLKL, and interaction between RIP1 and RIP3 were determined. Results showed hyperoxia exposure significantly caused damage to lung and increased necroptotic cells and the expression of RIP1, RIP3 and MLKL. Edaravone pre-treatment not only inhibited the oxidative stress in HALI, but also reduced necroptotic cells, decreased the expression of RIP1, RIP3 and MLKL and improved lung pathology. Nec-1 pretreatment inhibited necroptosis and improved lung pathology, but had little influence on oxidative stress. This study suggests hyperoxia exposure induces oxidative stress may activate necroptosis, involving in the pathology of HALI, and strategies targeting necroptosis may become promising treatments for HALI.

Case Report Serious pulmonary infection in a splenectomized patient with adult type 1 Gaucher disease.

A 49-year-old man with a history of Gaucher disease type 1, resulting in serious splenomegaly and eating disorder, was referred to our department and underwent a splenectomy under general anesthesia. Gaucher disease is very rare, and its first signs are unexplained splenomegaly and hypersplenism. On preoperative examination, the patient's platelet count was slightly low, and his other test results were normal. Surprisingly, on the first postoperative day, the patient developed a lung infection. This gradually progressed to acute respiratory distress syndrome with respiratory failure, requiring intubation and mechanical ventilation. The patient eventually recovered, and he was discharged after receiving antibiotics and other treatments to enhance immunity. However, his postoperative lung infection led to a significantly prolonged and expensive hospital stay. This case suggests that we must pay close attention to the immune dysfunction of patients with Gaucher disease type 1. Anesthesia and surgery with accompanying post-traumatic stress can weaken patients' immunity and cause susceptibility to severe lung infections. Pulmonary signs and functions should be monitored closely during the perioperative period, and, if necessary, gamma globulin and thymosin should be administered early in the preoperative or postoperative period to enhance immunity.

Gene expression profiling in human insulinoma tissue: genes involved in the insulin secretion pathway and cloning of novel full-length cDNAs.

Insulinoma is a clinically common cause of organic hypoglycemia. The prominent characteristic of insulinoma is endogenous hyperinsulinism. Until now, the molecular biology of human insulinoma has been little understood. In this study, gene expression profiling of human insulinoma was established by expressed sequence tag (EST) sequencing and cDNA array. A total of 2063 clones were obtained, of these, 1589 clones were derived from EST sequencing, 975 clones were derived from cDNA array and 501 clones were shared by the two methods. G protein alpha-stimulating activity polypeptide (Gsalpha) and carboxypeptidase E (CPE) were the most highly expressed genes in human insulinoma, as derived by EST sequencing and cDNA array respectively. The genes involved in the protein/insulin secretion pathway were strongly expressed in human insulinoma tissue. Meanwhile, eight full-length cDNAs of novel genes were cloned and sequenced. The results demonstrated the molecular biology of human insulinoma tissue at the level of transcript abundance and validated the efficacy of EST sequencing combined with cDNA array in the construction of gene expression profiling. In conclusion, the predominance of the genes participating in the secretory pathway suggested that regulation of secretion might be a major mechanism by which insulin release is abnormally increased in patients with insulinomas. It was also concluded that overexpression of the Gsalpha gene played an important role in the pathogenesis of insulinoma.