Interleukin-27 is a pleiotropic cytokine that is involved in tissue responses to infection,cell stress,neuronal disease,and tumors.Recent studies in various tissues indicate that interleukin-27 has complex activating ...Interleukin-27 is a pleiotropic cytokine that is involved in tissue responses to infection,cell stress,neuronal disease,and tumors.Recent studies in various tissues indicate that interleukin-27 has complex activating and inhibitory properties in innate and acquired immunity.The availability of recombinant interleukin-27 protein and mice with genetic deletions of interleukin-27,its receptors and signaling mediators have helped define the role of interleukin-27 in neurodegenerative diseases.Interleukin-27 has been well-characterized as an important regulator of T cell activation and differentiation that enhances or suppresses T cell responses in autoimmune conditions in the central nervous system.Evidence is also accumulating that interleukin-27 has neuroprotective activities in the retina and brain.Interleukin-27 is secreted from and binds to infiltrating microglia,macrophage,astrocytes,and even neurons and it promotes neuronal survival by regulating pro-and anti-inflammatory cytokines,neuroinflammatory pathways,oxidative stress,apoptosis,autophagy,and epigenetic modifications.However,interleukin-27 can have the opposite effect and induce inflammation and cell death in certain situations.In this review,we describe the current understanding of regulatory activities of interleukin-27 on cell survival and inflammation and discuss its mechanisms of action in the brain,spinal cord,and retina.We also review evidence for and against the therapeutic potential of interleukin-27 for dampening harmful neuroinflammatory responses in central nervous system diseases.展开更多
目的描绘弥漫型胃癌组织中组蛋白H3第27位赖氨酸的三甲基化(H3K27me3)修饰的全基因组分布图谱,通过鉴定H3K27me3所调控的关键靶基因,初步探究H3K27me3修饰重编程可能调控弥漫型胃癌细胞发生发展的作用机制。方法样本来源于2021-2023年...目的描绘弥漫型胃癌组织中组蛋白H3第27位赖氨酸的三甲基化(H3K27me3)修饰的全基因组分布图谱,通过鉴定H3K27me3所调控的关键靶基因,初步探究H3K27me3修饰重编程可能调控弥漫型胃癌细胞发生发展的作用机制。方法样本来源于2021-2023年在陆军特色医学中心消化内科内镜中心及手术室胃肠外科组接受检查或治疗的患者。共收集到正常组患者14例,其中男性6例,女性8例,平均年龄46岁;胃癌组患者14例,其中男性8例,女性6例,平均年龄63岁。采用染色质靶向剪切及转座酶技术(cleavage under target and tagmentation,CUT&Tag)捕获基因组H3K27me3修饰区域,分析H3K27me3修饰重编程特征。整合转录组(RNA‐Seq)测序数据、高通量染色体构象捕获技术(high‐throughput chromosome conformation capture,Hi‐C)及已发表的公共单细胞数据,分析H3K27me3修饰重编程在弥漫型胃癌细胞中所调控靶基因。结果CUT&Tag和RNA测序数据质量符合下游分析标准,正常胃黏膜组织和弥漫型胃癌组织的组蛋白H3K27me3修饰均主要分布于远端基因间区和内含子区。相较于正常组织,胃癌组织的H3K27me3修饰存在显著的重编程特征,表现为H3K27me3总体信号强度明显降低。其中缺失的2912个H3K27me3信号峰可能导致822个肿瘤相关基因的表达上调,这些基因中上调最显著(信号值强度的差异倍数≥2,P<0.05)的56个基因主要富集于哺乳动物雷帕霉素靶蛋白复合体1(mammalian target of rapamycin complex 1,mTORC1)信号通路,其中甲硫氨酸转运体SLC7A5和胱氨酸转运体SLC7A11在胃癌组织中的表达最高。单细胞数据提示,弥漫型胃癌组织中SLC7A11的异常高表达主要存在于肿瘤上皮细胞。利用公共数据和免疫组织化学实验进一步验证SLC7A11在弥漫型胃癌中高表达,且与胃癌患者的不良预后相关。结论组蛋白H3K27me3修饰重编程是弥漫型胃癌的重要表观遗传学特征;组蛋白H3K27me3修饰缺失可能上调肿瘤细胞SLC7A11表达,进而促进肿瘤进展。展开更多
目的:比较25G和27G玻璃体切割系统治疗累及黄斑区孔源性视网膜脱离的疗效、安全性及并发症。方法:回顾性分析2021-01/2023-12于我院首次诊断为孔源性视网膜脱离(脱离范围累及黄斑区)并且接受25G或27G玻璃体切割联合视网膜复位的患者60...目的:比较25G和27G玻璃体切割系统治疗累及黄斑区孔源性视网膜脱离的疗效、安全性及并发症。方法:回顾性分析2021-01/2023-12于我院首次诊断为孔源性视网膜脱离(脱离范围累及黄斑区)并且接受25G或27G玻璃体切割联合视网膜复位的患者60例60眼,根据术中使用玻璃体切割系统不同分为25G组30例30眼术中使用25G玻璃体切割系统进行手术操作;27G组30例30眼术中使用27G玻璃体切割系统进行手术操作。术后随访6 mo,比较两组患者手术前后最佳矫正视力(BCVA)、眼压、手术操作时间、视网膜复位情况、并发症。结果:27G组患者平均手术时间略长于25G组(40.20±7.52 vs 36.97±7.47 min),25G组术中出现切口渗漏7眼(23%)高于27G组1眼(3%),但两组间无差异(P>0.05)。术后6 mo,27G组和25G组患者BVCA(LogMAR)(0.37±0.19 vs 0.40±0.17)均较术前(0.98±0.32 vs 0.84±0.33)改善(均P<0.05),两组间术后BCVA无差异(P>0.05)。术后1 d时25G组平均眼压(12.29±2.86 mmHg)低于27G组(15.87±3.70 mmHg,P<0.001),术后1 wk,1 mo时两组间平均眼压比较均无差异(均P>0.05)。两组患者术后不同时间视网膜复位情况,术中与术后并发症比较均无差异(均P>0.05)。结论:25G和27G玻璃体切割术是一种安全有效的治疗孔源性视网膜脱离方法。但27G玻璃体切割系统具有切口小、自闭性好、眼压稳定等优势。展开更多
基金support for this work for ASH was from National Eye Institute R01 EY026546an NEI Center Core Grant EY014801.
文摘Interleukin-27 is a pleiotropic cytokine that is involved in tissue responses to infection,cell stress,neuronal disease,and tumors.Recent studies in various tissues indicate that interleukin-27 has complex activating and inhibitory properties in innate and acquired immunity.The availability of recombinant interleukin-27 protein and mice with genetic deletions of interleukin-27,its receptors and signaling mediators have helped define the role of interleukin-27 in neurodegenerative diseases.Interleukin-27 has been well-characterized as an important regulator of T cell activation and differentiation that enhances or suppresses T cell responses in autoimmune conditions in the central nervous system.Evidence is also accumulating that interleukin-27 has neuroprotective activities in the retina and brain.Interleukin-27 is secreted from and binds to infiltrating microglia,macrophage,astrocytes,and even neurons and it promotes neuronal survival by regulating pro-and anti-inflammatory cytokines,neuroinflammatory pathways,oxidative stress,apoptosis,autophagy,and epigenetic modifications.However,interleukin-27 can have the opposite effect and induce inflammation and cell death in certain situations.In this review,we describe the current understanding of regulatory activities of interleukin-27 on cell survival and inflammation and discuss its mechanisms of action in the brain,spinal cord,and retina.We also review evidence for and against the therapeutic potential of interleukin-27 for dampening harmful neuroinflammatory responses in central nervous system diseases.
文摘目的描绘弥漫型胃癌组织中组蛋白H3第27位赖氨酸的三甲基化(H3K27me3)修饰的全基因组分布图谱,通过鉴定H3K27me3所调控的关键靶基因,初步探究H3K27me3修饰重编程可能调控弥漫型胃癌细胞发生发展的作用机制。方法样本来源于2021-2023年在陆军特色医学中心消化内科内镜中心及手术室胃肠外科组接受检查或治疗的患者。共收集到正常组患者14例,其中男性6例,女性8例,平均年龄46岁;胃癌组患者14例,其中男性8例,女性6例,平均年龄63岁。采用染色质靶向剪切及转座酶技术(cleavage under target and tagmentation,CUT&Tag)捕获基因组H3K27me3修饰区域,分析H3K27me3修饰重编程特征。整合转录组(RNA‐Seq)测序数据、高通量染色体构象捕获技术(high‐throughput chromosome conformation capture,Hi‐C)及已发表的公共单细胞数据,分析H3K27me3修饰重编程在弥漫型胃癌细胞中所调控靶基因。结果CUT&Tag和RNA测序数据质量符合下游分析标准,正常胃黏膜组织和弥漫型胃癌组织的组蛋白H3K27me3修饰均主要分布于远端基因间区和内含子区。相较于正常组织,胃癌组织的H3K27me3修饰存在显著的重编程特征,表现为H3K27me3总体信号强度明显降低。其中缺失的2912个H3K27me3信号峰可能导致822个肿瘤相关基因的表达上调,这些基因中上调最显著(信号值强度的差异倍数≥2,P<0.05)的56个基因主要富集于哺乳动物雷帕霉素靶蛋白复合体1(mammalian target of rapamycin complex 1,mTORC1)信号通路,其中甲硫氨酸转运体SLC7A5和胱氨酸转运体SLC7A11在胃癌组织中的表达最高。单细胞数据提示,弥漫型胃癌组织中SLC7A11的异常高表达主要存在于肿瘤上皮细胞。利用公共数据和免疫组织化学实验进一步验证SLC7A11在弥漫型胃癌中高表达,且与胃癌患者的不良预后相关。结论组蛋白H3K27me3修饰重编程是弥漫型胃癌的重要表观遗传学特征;组蛋白H3K27me3修饰缺失可能上调肿瘤细胞SLC7A11表达,进而促进肿瘤进展。
文摘目的探究急性ST段抬高型心肌梗死(ST-segment elevation myocardial infarction,STEMI)患者外周血微小核糖核酸(microRNA,miRNA)-145-5p、miR-27b-3p浓度对经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗后并发心力衰竭(heart failure,HF)的预测价值。方法选择于2021年1月至2023年2月于成都市第五人民医院就诊的STEMI患者176例(均行PCI治疗)作为观察对象,观察STEMI患者PCI治疗后HF的发生情况,分为发生组和未发生组。实时定量聚合酶链反应(quantitative real time polymerase chain reaction,qRT-PCR)法检测外周血miR-145-5p、miR-27b-3p浓度。Pearson法、Spearman法分析血清miR-145-5p、miR-27b-3p及二者与一般资料的相关性。STEMI患者发生HF的影响因素采用多因素Logistic回归分析。绘制受试者工作特征曲线(receiver operating characteristic curve,ROC)分析血清miR-145-5p、miR-27b-3p对STEMI患者PCI治疗后发生HF的预测价值。结果两组患者的病变支数、血清同型半胱氨酸(homocysteine,Hcy)、超敏C反应蛋白(hypersensitive C-reactive protein,hs-CRP)浓度比较,差异有统计学意义(P<0.05)。发生组患者的血清miR-145-5p、miR-27b-3p浓度高于未发生组,差异有统计学意义(P<0.05)。根据Spearman相关性分析得知,血清miR-145-5p、miR-27b-3p浓度与病变支数呈正相关(P<0.05)。根据Pearson相关性分析得知,血清miR-145-5p浓度与miR-27b-3p浓度呈正相关(P<0.05);血清miR-145-5p、miR-27b-3p浓度与Hcy、hs-CRP浓度呈正相关(P<0.05)。多因素Logistic回归分析显示多支病变、Hcy、hs-CRP、miR-145-5p、miR-27b-3p为影响STEMI患者PCI治疗后发生HF的危险因素(P<0.05)。血清miR-145-5p预测STEMI患者PCI治疗后发生HF的曲线下面积(area under the curve,AUC)为0.896,血清miR-27b-3p预测STEMI患者PCI治疗后发生HF的AUC为0.883,二者联合预测STEMI患者发生HF的AUC为0.962,二者联合优于各自单独预测(P<0.05)。结论miR-145-5p、miR-27b-3p浓度升高与STEMI患者PCI治疗后发生HF相关,两者联合对STEMI患者PCI治疗后发生HF具有较高的预测价值。
文摘目的:比较25G和27G玻璃体切割系统治疗累及黄斑区孔源性视网膜脱离的疗效、安全性及并发症。方法:回顾性分析2021-01/2023-12于我院首次诊断为孔源性视网膜脱离(脱离范围累及黄斑区)并且接受25G或27G玻璃体切割联合视网膜复位的患者60例60眼,根据术中使用玻璃体切割系统不同分为25G组30例30眼术中使用25G玻璃体切割系统进行手术操作;27G组30例30眼术中使用27G玻璃体切割系统进行手术操作。术后随访6 mo,比较两组患者手术前后最佳矫正视力(BCVA)、眼压、手术操作时间、视网膜复位情况、并发症。结果:27G组患者平均手术时间略长于25G组(40.20±7.52 vs 36.97±7.47 min),25G组术中出现切口渗漏7眼(23%)高于27G组1眼(3%),但两组间无差异(P>0.05)。术后6 mo,27G组和25G组患者BVCA(LogMAR)(0.37±0.19 vs 0.40±0.17)均较术前(0.98±0.32 vs 0.84±0.33)改善(均P<0.05),两组间术后BCVA无差异(P>0.05)。术后1 d时25G组平均眼压(12.29±2.86 mmHg)低于27G组(15.87±3.70 mmHg,P<0.001),术后1 wk,1 mo时两组间平均眼压比较均无差异(均P>0.05)。两组患者术后不同时间视网膜复位情况,术中与术后并发症比较均无差异(均P>0.05)。结论:25G和27G玻璃体切割术是一种安全有效的治疗孔源性视网膜脱离方法。但27G玻璃体切割系统具有切口小、自闭性好、眼压稳定等优势。
