RESUMEN
BACKGROUND Sepsis has emerged as a leading cause of death in the intensive care unit. A growing number of studies have shown that genetic variants, especially single nucleotide polymorphisms, are key determinants of inter-individual variation in sepsis response. Therefore, early prediction of the onset and progression of sepsis, along with early intervention in high-risk patients, should be performed to effectively reduce the morbidity and mortality of the disease. MATERIAL AND METHODS A total of 581 Chinese patients were enrolled in this study, including 271 patients with sepsis and 310 patients without. We measured gene polymorphisms of MBL2 and serum levels of MBL2, tumor necrosis factor (TNF-alpha), interleukin (IL)-6, IL-4, and IL-10 in all patients. The effects of site mutations on the binding of MBL2 to mannose-associated serine protease 1 (MASP1) and MASP2 were also analyzed. RESULTS Of 3 site mutations in the MBL2 gene (rs5030737, rs1800450, and rs1800451), only rs1800450 had a mutant (G/A) genotype. The frequency of the GA genotype and A allele in the sepsis group was higher than that in the non-sepsis group. Furthermore, rs1800450G/A was associated with decreased serum MBL2 and IL-10 levels and decreased MBL2-MASP1 and MBL2-MASP2 interactions. Bioinformatics analysis showed that rs1800450G/A reduced the structural stability of the MBL2 protein and affected its function. CONCLUSIONS MBL2 rs1800450G/A was associated with a higher risk of sepsis, which possibly involved a decreased level of serum MBL2 that broke the balance of inflammation and weakened the binding of MBL2 to MASP1 and MASP2.
Asunto(s)
Lectina de Unión a Manosa , Sepsis , China , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Interleucina-10/genética , Lectina de Unión a Manosa/genética , Serina Proteasas Asociadas a la Proteína de Unión a la Manosa/genética , Polimorfismo de Nucleótido Simple/genética , Sepsis/genéticaRESUMEN
BACKGROUND: Neonates with moderate to severe encephalopathy benefit significantly from therapeutic hypothermia, with reduced risk of death or disability. However, the need for therapeutic hypothermia for mild neonatal encephalopathy (NE) remains unclear. Therefore, we conducted a protocol for systematic review and meta-analysis to provide evidence supporting therapeutic hypothermia for term or near term neonates with mild NE, including findings of recent long-term outcome studies, as well as novel adjunctive therapies to augment neurodevelopmental outcomes for neonates with NE who receive therapeutic hypothermia. METHODS: Two independent researchers performed a systematic literature search in different electronic databases including PubMed, the Cochrane Center Controlled Trials Register, EMBASE, Medline, Ovid, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wanfang Database without any restrictions of languages and date. Two reviewers will screen the records and include quality studies according to inclusion criteria independently. Two reviewers will assess the risk of bias of the included studies by the "Risk of Bias Assessment Tool" of the Cochrane Handbook for randomized controlled trials. Statistical analysis will be performed with Review Manager software 5.3. RESULTS: A synthesis of current evidence of therapeutic hypothermia for treating mild NE will be provided in this protocol. CONCLUSION: The results of this study will provide a theoretical basis for the clinical use of therapeutic hypothermia in mild NE.