Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life ...Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.展开更多
目的以24 h尿钠排泄水平(24 h UNa)作为钠摄入量评估指标,评估不同钠盐的摄入水平与血清炎症因子对2型糖尿病(T2DM)患者尿白蛋白(UA)发生风险的影响。方法纳入T2DM患者130例,依据尿白蛋白/肌酐比值(UACR)水平分为UA阳性组60例和UA阴性...目的以24 h尿钠排泄水平(24 h UNa)作为钠摄入量评估指标,评估不同钠盐的摄入水平与血清炎症因子对2型糖尿病(T2DM)患者尿白蛋白(UA)发生风险的影响。方法纳入T2DM患者130例,依据尿白蛋白/肌酐比值(UACR)水平分为UA阳性组60例和UA阴性组70例。收集患者的临床资料,检测炎性因子及24 h尿液相关指标。采用Spearman相关分析T2DM患者临床指标与UACR的相关性;二元Logistic回归分析T2DM患者临床指标对UA的影响;二分类回归法分析24 h UNa和IL-18关联对UA的影响。结果24 h UNa水平(OR=1.019,95%CI 1.003~1.035,P=0.017)与IL-18(OR=1.204,95%CI 1.060~1.368,P=0.004)是T2DM患者UA阳性的独立危险因素。联合分析提示,与低钠低IL-18组比较,高钠高IL-18组UA阳性风险显著增加(OR=10.774,95%CI 2.105~55.155,P=0.004)。结论24 h UNa、IL-18水平升高是T2DM患者UA发生的危险因素。展开更多
基金supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG)the Key Talent Project for Strengthening Health during the 13^(th)Five-Year Plan Period,No.ZDRCA2016069(to XG)+1 种基金the National Key R&D Program of China,No.2018YFC2001901(to XG)Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。
文摘Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.
文摘目的以24 h尿钠排泄水平(24 h UNa)作为钠摄入量评估指标,评估不同钠盐的摄入水平与血清炎症因子对2型糖尿病(T2DM)患者尿白蛋白(UA)发生风险的影响。方法纳入T2DM患者130例,依据尿白蛋白/肌酐比值(UACR)水平分为UA阳性组60例和UA阴性组70例。收集患者的临床资料,检测炎性因子及24 h尿液相关指标。采用Spearman相关分析T2DM患者临床指标与UACR的相关性;二元Logistic回归分析T2DM患者临床指标对UA的影响;二分类回归法分析24 h UNa和IL-18关联对UA的影响。结果24 h UNa水平(OR=1.019,95%CI 1.003~1.035,P=0.017)与IL-18(OR=1.204,95%CI 1.060~1.368,P=0.004)是T2DM患者UA阳性的独立危险因素。联合分析提示,与低钠低IL-18组比较,高钠高IL-18组UA阳性风险显著增加(OR=10.774,95%CI 2.105~55.155,P=0.004)。结论24 h UNa、IL-18水平升高是T2DM患者UA发生的危险因素。
