疟疾患者血浆IgG N-糖基化水平异常修饰的病例对照研究

目的 探索疟疾患者与健康人群血浆中免疫球蛋白G(IgG)N-聚糖表达水平的差异性。方法 选择山东省2022年10月-2023年6月确诊的输入性疟疾(排除合并细菌感染)患者27例,健康对照组采用倾向性评分1∶1匹配,最终纳入55例。抽取受检者静脉血,肝素抗凝,分离血浆,提取IgG,采用超高液相色谱法检测IgG N-糖基组。组间糖基结构比较采用两独立样本t检验或Mann-Whitney U秩和检验,P<0.05为差异有统计学意义。结果 55例受检者的年龄范围为27(56岁,平均年龄(41.64±8.64)岁。疟疾病例组患者血浆GP4、GP6、GP14、GP17和GP19的聚糖水平均显著高于对照组(P<0.05或P<0.01);GP5、GP8、GP9、GP11、GP13-GP18、GP20、GP21、GP23和GP14的聚糖水平均显著低于对照组(P<0.05或P<0.01)。IgG无半乳糖基化(G0)水平疟疾病例组为(28.42±7.07),健康对照组为22.34±5.54;IgG单半乳糖基化(G1)水平疟疾病例组为25.61±4.08,健康对照组,32.85±...     

HBV相关肝细胞癌患者血清N-糖组图谱改变与肝组织糖基转移酶表达变化的关系

目的本研究通过对HBV相关肝细胞癌(HCC)患者血清N-聚糖检测及肝癌组织与癌旁组织中糖基转移酶基因表达水平比较分析,探索HCC患者血清N-聚糖变化的可能机制。方法收集解放军总医院2018年—2019年HBV相关HCC手术患者(34例)的肝癌和癌旁组织及正常肝组织标本,同时采集血清标本。从34例HCC患者中随机选择8例HCC患者血清标本作为HCC试验组,20例健康成年人血清标本作为对照组。应用DSA-FACE法分析HCC试验组与对照组血清N-聚糖图谱。采用荧光定量PCR法检测34例HBV相关HCC患者癌组织和癌旁组织中8种糖基转移酶基因(FUT3、FUT4、FUT6、FUT7、FUT8、Gn-TⅢ、Gn-TⅣa和Gn-TⅤ) mRNA表达水平,并应用蛋白印迹法检测相应蛋白表达水平。计量资料两组间比较采用独立样本t检验。结果与对照相比,8例HCC患者血清中N-聚糖峰9 (peak9,NA3Fb)的丰度明显升高(t=-2.514,P 0.05)。糖基转移酶FUT8、Gn-TⅣa和Gn-TⅤ基因mRNA表达水平在癌组织和癌旁组织间有差异,其中癌组织中FUT8和Gn-TⅤ基因的mRNA与蛋白表达水平显著高于癌旁组织(mRNA:1.50±0.34 vs 0.65±0.11,t=-2.354,P=0.022; 3.57±0.64 vs 1.33±0.16,t=-3.384,P=0.001)(蛋白:0.70±0.11 vs 0.083±0.017,t=9.555,P=0.001; 1.33±0.19 vs 0.60±0.15,t=5.097,P=0.007);癌组织中GnTⅣa基因的mRNA表达水平显著高于癌旁组织(mRNA:2.90±0.47 vs 1.68±0.19,t=-2.403,P=0.019),蛋白表达水平与癌旁组织无显著差异(蛋白:0.52±0.24 vs 0.24±0.11,t=1.833,P=0.141)。癌组织中这些糖基转移酶表达改变与血清中N-聚糖丰度变化一致。结论 HBV相关HCC患者血清中一些N-聚糖水平变化可能与肝癌组织中糖基转移酶基因GnT-V、GnT-IVa和FUT8表达上调密切相关。     

黏蛋白型O-糖基化与结直肠癌基础和临床研究进展

O-糖基化为黏蛋白常见的翻译后修饰,普遍存在于正常细胞和肿瘤细胞中。结直肠癌（CRC）细胞内O-糖基化相关的糖基转移酶、分子伴侣和表面的Tn抗原、sTn抗原、T抗原出现不同程度的失调,且以其特有方式参与CRC的发生、发展,包括侵袭和转移、异常凋亡和增殖、免疫逃逸等,并作为新型肿瘤生物学标志物和潜在治疗靶点被广泛研究。本文就黏蛋白型O-糖基化与CRC的发生、发展及其临床应用的研究进展作一综述。     

糖尿病患者的N-糖组学研究进展

N-糖组学主要是研究机体内N-聚糖结构和功能的一门新兴学科, 近年来N-糖组改变与各种疾病相关性研究日益增多。糖尿病是世界范围内发病率较高的慢性疾病, 糖尿病患者体内普遍出现多种病理生理学变化及代谢紊乱, 以糖代谢紊乱最为突出。目前有较多研究报道, 糖尿病与N-糖组改变相关, 糖尿病患者血清中N-糖蛋白的数量、结构和免疫球蛋白G N-聚糖发生了改变, 并表明N-聚糖有可能作为糖尿病生物标志物。该文就目前糖尿病的N-糖组学相关研究进展作一简要综述。     

O连接N-乙酰氨基葡萄糖糖基化修饰与糖尿病肾病的关系

O连接N-乙酰氨基葡萄糖（O-GlcNAc）糖基化修饰是一种常见的蛋白质翻译后修饰,其在胰岛素抵抗及糖尿病并发症中发挥着重要作用。近年来相关研究证明O-GlcNAc糖基化修饰与糖尿病肾病密切相关,高糖状态下进入氨基己糖生物合成途径的葡萄糖通量增加,O-GlcNAc糖基化修饰水平增加,其通过修饰特定的蛋白,诱导基底膜损伤...     

Signaling pathway/molecular targets and new targeted agents under development in hepatocellular carcinoma

Advances in molecular cell biology over the last decade have clarified the mechanisms involved in cancer growth,invasion,and metastasis,and enabled the development of molecular-targeted agents.To date,sorafenib is the only molecular-targeted agent whose survival benefit has been demonstrated in two global phase Ⅲ randomized controlled trials,and has been approved worldwide.Phase Ⅲ clinical trials of other molecular targeted agents comparing them with sorafenib as first-line treatment agents are ongoing.Those agents target the vascular endothelial growth factor,platelet-derived growth factor receptors,as well as target the epidermal growth factor receptor,insulinlike growth factor receptor and mammalian target of rapamycin,in addition to other molecules targeting other components of the signal transduction pathways.In addition,the combination of sorafenib with standard treatment,such as resection,ablation,transarterial embolization,and hepatic arterial infusion chemotherapy are ongoing.This review outlines the main pathways involved in the development and progression of hepatocellular carcinoma and the new agents that target these pathways.Finally,the current statuses of clinical trials of new agents or combination therapy with sorafenib and standard treatment will also be discussed.     

Pleiotropic effects of statins in the diseases of the liver

Statins are a class of molecules that inhibit HMG Co A reductase. They are usually prescribed as a lipid lowering medication. However, there is accumulating evidence that statins have multiple secondary effects both related and unrelated to their lipid-lowering effect. This narrative review of the literature aims to provide the reader with information from clinical studies related to the effect of statin and statins' potential use in patients with liver diseases. In patients with advanced liver disease due to any etiology, statins exhibit an antifibrotic effect possibly through the prevention of hepatic sinusoidal microthrombosis. Two randomized controlled trials confirmed that statins decrease hepatic vein pressure gradient in patients with portal hypertension and improve the survival of patients after variceal bleeding. Lower rates of infections were observed in patients with cirrhosis who received statin treatment. Statins decrease the risk of hepatocellular carcinoma(HCC) in patients with advanced liver disease in general but particularly in patients with chronic hepatitis B and C. Statins in patients with chronic hepatitis C likely increase the virological response to the treatment with pegylated interferon and ribavirin and have the potential to decrease the rate of fibrosis. Finally, data from randomized controlled trials also confirmed that the addition of statin prolongs the survival of patients with advanced HCC even more than sorafenib. Statins are a very promising group of drugs especially in patients with liver disease, where therapeutic options can often be limited. Some indications, such as the prevention of re-bleeding from esophageal varices and the palliative treatment of HCC have been proven through randomized controlled trials, while additional indications still need to be confirmed through prospective studies.     

血清肝细胞生长因子在慢性肝病中的意义

目的 肝细胞生长因子(HGF)能促进上皮细胞增生、运动、变形，是肝再生的起始因子之一，近来发现其在肝硬化和肝肿瘤的发生发展中也有重要作用。现主要探讨血清HGF水平在慢性肝病中的意义。方法 检测197例个体血清HGF水平，包括肝细胞癌(HCC)80例，肝硬化(LC)57例，慢性肝炎(CH)22例，正常对照38例。ELISA法检测血清HGF水平，并描绘受试者工作曲线(ROC)，确定HCC和LC患者HGF水平的最佳临界点。运用Spearman相关分析HGF水平和ALT、AST、GGT、白蛋白、总胆红索、凝血时间、肝癌大小、病理分级的相关性。结果 HCC、LC、CH和正常对照组的血清HGF中位值分别是6．767、151．200、7．017和3．476pg／m1。其中HCC组(P＜0．05)和比组(P＜0．01)的血清HGF水平显著高于正常对照组。LC组根据Child分级分层发现，Child C级患者的HGF水平明显高于Child A、B级。肝硬化ROC曲线显示，14pg／m1为临界值时效率最高。血清HGF水平仅发现与凝血时间有相关性(r=0．45，P＜0．01)。在HCC组中，未发现血清HGF水平与肿瘤大小、病理分级有任何相关。结论 血清中HGF水平增高与LC程度有关。     

非酒精性脂肪性肝病与肝细胞癌发生

肝细胞癌的发病率在全球逐年升高。绝大多数肝细胞癌与肝炎病毒感染有关,然而非酒精性脂肪性肝病也是引起肝细胞癌的重要原因之一。近年来,随着饮食习惯及生活方式的改变,非酒精性脂肪性肝病发病率持续升高,其与肝细胞癌发生的关系也得到了更多的关注。本文主要从非酒精性脂肪性肝病相关肝细胞癌的发病进程、危险因素及发病机制等方面做一介绍。     

DNA methylation in liver diseases

Recently, growing evidences show that the combination of epigenetic and genetic abnormalities contribute together to the development of liver diseases. DNA methylation is a very important epigenetic mechanism in human beings. It refers to addition of the methyl groups to DNA and mainly occurs at cytosine adjacent to guanine. DNA methylation is prevalent across human genome and is essential for the normal human development, while its dysfunction is associated with many human diseases. A deep understanding of DNA methylation may provide us deep insight into the origination of liver diseases. Also, it may provide us new tools for diseases diagnosis and prognosis prediction. This review summarized recent progress of DNA methylation study and provided an overview of DNA methylation and liver diseases. Meanwhile, the association between DNA methylation and liver diseases including hepatocellular carcinoma, liver fibrosis, nonalcoholic steatohepatitis and liver failure were extensively discussed. Finally, we discussed the potential of DNA methylationtherapeutics for liver diseases and the value of DNA methylation as biomarkers for liver diseases diagnosis and prognosis prediction. This review aimed to provide the emerging DNA methylation information about liver diseases. It might provide essential information for managing and care of these patients.     

N-Glycan profiling in the study of human aging

Most secreted proteins produced by the human body are modified by glycosylation. It is well known that the oligosaccharides (glycans) of glycoproteins are important for initiation of various cellular recognition signals that are essential for the maintenance of the ordered social life of each cell within a multi-cellular organism. The sugar chains can be altered by the physiological or pathophysiological condition of the cell. We describe a detailed protocol for the analysis of N-linked glycans in blood via DNA sequencing equipment-Fluorophore Assisted Carbohydrate Electrophoresis (DSA-FACE). The key features of this technique are its robustness, high throughput, high sensitivity and reliable quantification. Based on DSA-FACE technology, we previously reported that N-glycan profiling of the human serum shows substantial changes with increasing age in three major N-glycan structures. We proposed that measurement of the N-glycan level changes could provide a surrogate marker for general health or for age-related disease progression, and for monitoring the improvement of health after therapy.     

Association study of genetic variations in microRNAs with the risk of hepatitis B-related liver diseases

Background and aims

MicroRNAs have been recently identified as important regulators that influence human carcinogenesis, cancer progression, and the interaction between the host and virus. This study investigates an association between microRNAs (miR-101-1, miR-101-2, and miR-338) and the risk of liver diseases through clearance of hepatitis B virus infection, development of liver cirrhosis, and hepatocellular carcinoma occurrence.

Methods

Genetic variations were genotyped using the TaqMan assay in 1439 Korean hepatitis B virus patients. To investigate the relationship between four polymorphisms in three microRNAs and the disease phenotypes, differences in frequency distribution of variations were analysed using logistic and multiple regression analyses after adjusting for age and gender as covariates.

Results

We find that the rs7536540 polymorphism in miR-101-1 is significantly associated with development of liver cirrhosis and hepatocellular carcinoma occurrence. In addition, rs12375841 and its unique haplotype (ht2) in miR-101-2 show significant association with clearance of hepatitis B virus infection.

Conclusions

To our knowledge, this is the first study to examine a relationship between the three microRNA genes and the risk of hepatitis B-related liver diseases. We expect that the findings in this study will be helpful to further genetic studies in the pathophysiology of hepatitis B virus-related liver diseases.     

磷脂酰肌醇蛋白聚糖3在肝穿刺活检标本中鉴别诊断的意义

目的:探讨磷脂酰肌醇蛋白聚糖3(GPC3)在肝细胞癌(HCC)等不同肝病组织中的表达情况及其对肝癌早期诊断的意义.方法:采用免疫组织化学方法检测126例肝穿刺活检标本(包括13例极早期HCC、44例早期HCC、16例不典型增生、29例肝硬化和24例肝炎)及57例中晚期HCC手术标本中GPC3和甲胎蛋白(AFP)的表达,...     

Value of serum C-reactive protein measurement in the detection of hepatocellular carcinoma superimposed on liver cirrhosis

We investigated whether, in Italian patients, C-reactive protein (CRP) determination could be considered a useful adjunct, complementary to ₁-fetoprotein, in the detection of liver cancer. CRP was determined by particle-enhanced nephelometry in 171 subjects (102 male, 69 female). Fifty-five patients had mild chronic liver disease (CLD), 45 cirrhosis (CIR), 38 hepatocellular carcinoma (HCC); 33 subjects were healthy controls. Patients with HCC and CIR had higher CRP levels (P<0.05) than those found in patients with CLD and controls. CRP higher than 5 mg/l was found in 30/38 (78.9%) patients with HCC, 28/45 (62.2%) patients with CIR, 16/55 (29.1%) patients with CLD (² 56.0,P<0.0001). Sensitivity, specificity and diagnostic accuracy of CRP in diagnosing HCC with respect to CLD+CIR were: 78.9%, 56.0% and 34.9%. However, when considered only in the subgroup of patients with ₁-fetoprotein below or equalling 30 ng/ml, they were 50.0%, 54.3% and 4.3% respectively. In conclusion, CRP concentration is frequently elevated in patients with HCC, however, it does not seem to improve the ability of ₁-fetoprotein to discriminate HCC from CIR.