创伤性脑损伤患者脑脊液中嗜中性白细胞碱性磷酸酶-1的表达及意义

目的探讨炎性体蛋白嗜中性白细胞碱性磷酸酶-1(NALP-1)在创伤性脑损伤患者脑脊液中表达水平及其与预后相关性。方法选取2017年2月至2018年9月来自首都医科大学附属北京同仁医院的120例创伤性脑损伤患者,选取同期健康体检者30例作为对照组,采用免疫印迹化学发光法检测研究对象脑脊液中炎性体蛋白NALP-1表达水平,根据格拉斯哥预后评分(GOS)将创伤性脑损伤患者分为预后良好组(GOS>3分)和预后不良组(GOS≤3分)。χ^(2)检验和t检验分析预后良好组和预后不良组NALP-1和临床资料差异,采用多因素Logistic回归模型分析创伤性脑损伤后患者预后影响因素。结果创伤性脑损伤患者脑脊液中NALP-1表达(1.64±0.52)高于对照组(0.94±0.28,t=7.108,P<0.05),差异有统计学意义。NALP-1高表达组急性生理与慢性健康状况评分Ⅱ(APACHEⅡ)得分(26.4±5.4)分、脑挫伤比例(76.62%)、蛛网膜下腔出血比例(77.27%)高于低表达组[(22.3±4.5)分、23.38%、22.73%],差异有统计学意义(χ^(2)/t=4.135、9.586、7.424,P<0.05)。年龄[比值比(OR):2.175,95%可信区间(CI):1.167~8.767,P<0.05]、蛛网膜下腔出血(OR:1.241,95%CI:1.101~3.794,P<0.05)、NALP-1(OR:2.841,95%CI:1.675~10.717,P<0.05)、纤维蛋白原水平(OR:1.215,95%CI:1.056~3.627,P<0.05)、APACHEⅡ得分(OR:1.615,95%CI:1.314~5.485,P<0.05)是预后不良独立影响因素,差异均有统计学意义。结论创伤性脑损伤脑脊液中NALP-1表达增加,且表达量升高与预后不良相关。

Oxymatrine liposome attenuates hepatic fibrosis via targeting hepatic stellate cells

AIM： To investigate the potential mechanism of Arg- Gly-Asp （RGD） peptide-labeled liposome loading oxy- matrine （OM） therapy in CCI4-induced hepatic fibrosis in rats. METHODS： We constructed a rat model of CCh- induced hepatic fibrosis and treated the rats with dif- ferent formulations of OM. To evaluate the antifibrotic effect of OM, we detected levels of alkaline phospha- tase, hepatic histopathology （hematoxylin and eosin stain and Masson staining） and fibrosis-related gene expression of matrix metallopeptidase （MMP）-2, tis- sue inhibitor of metalloproteinase （TIMP）-I as well as type I procollagen via quantitative real-time poly- merase chain reaction. To detect cell viability and apop- tosis of hepatic stellate cells （HSCs）, we performed 3-（4,5）-dimethylthiahiazo（-z-yl）-3,5-diphenytetrazoli- umromide assay and flow cytometry. To reinforce the combination of oxymatrine with HSCs, we constructed fluorescein-isothiocyanate-conjugated Arg-Gly-Asp peptide-labeled liposomes loading OM, and its targeting of HSCs was examined by fluorescent microscopy. RESULTS： OM attenuated CCh-induced hepatic fibro- sis, as defined by reducing serum alkaline phosphatase （344.47± 27.52 U/L vs 550.69 ± 43.78 U/L, P 〈 0.05）, attenuating liver injury and improving collagen deposits （2.36% ± 0.09% vs 7.70% ±0.60%, P 〈 0.05） and downregulating fibrosis-related gene expression, that is, MMP-2, TIMP-1 and type I procollagen （P 〈 0.05）. OM inhibited cell viability and induced apoptosis of HSCs in vitro. RGD promoted OM targeting of HSCs and en- hanced the therapeutic effect of OM in terms of serum alkaline phosphatase （272.51 ± 19.55 U/L vs 344.47 ± 27.52 U/L, P 〈 0.05）, liver injury, collagen deposits （0.26%± 0.09% vs 2.36% ± 0.09%, P 〈 0.05） and downregulating fibrosis-related gene expression, that is, MMP-2, TIMP-1 and type I procollagen （P 〈 0.05）. Moreover, in vitro assay demonstrated that RGD en- hanced the effect of OM on HSC viability and apoptosis. CONCLUSION： OM attenuated hepatic fibrosis by in- hibiting viability and inducing apoptosis of HSCs. The RGD-labeled formulation enhanced the targeting effi- ciency for HSCs and the therapeutic effect.

血浆长链非编码RNA H19在原发性肝癌诊断中的价值

目的探讨血浆长链非编码RNA印迹母系表达转录体(H19)在原发性肝癌(primary hepatic carcinoma,PHC)中的临床诊断意义。方法收集并检测180例PHC患者和211例非肝癌患者血浆中H19、甲胎蛋白(AFP)、γ-谷氨酰基转氨酶2(γ-GT2)、异常凝血酶原(AP)、α-L-岩藻糖苷酶(AFU)和碱性磷酸酶-1(ALP-1)的表达水平,Logistic回归和受试者工作(ROC)曲线分析其特异性、灵敏度等指标。结果 H19在PHC患者血浆中的表达水平明显升高,差异有统计学意义(P<0.01);H19的AUC值为0.868,约登指数为0.702,H19相对表达水平临界阈值设定为0.073时,诊断灵敏度为77.78%,特异度为92.42%;H19+AFP的AUC为0.949,灵敏度为86.11%,特异度为92.42%,约登指数为0.753,其约登指数最高;H19+AFP+γ-GT2联合检测时,AUC可达0.961,灵敏度为91.67%,特异度为91.00%,约登指数为0.827。结论 H19在PHC患者中表达水平明显升高并可作为PHC临床诊断的独立标志物;H19+AFP+γ-GT2联合检测具有较好的诊断效能。