髓系来源的抑制细胞在肝病发病中的作用研究进展*

髓系来源的抑制细胞来源于骨髓祖细胞和未成熟的髓系细胞。近年来的研究表明,该细胞参与调节多种肝脏疾病的病理变化。本文系统地归纳了髓系来源的抑制细胞的历史、分群、作用机制和当前该细胞在各种肝病发病中的免疫调控作用及其与疾病进展的关系。     

Phylogenetic analysis of hepatitis delta virus isolated from HBsAg positive patients in Shahrekord,Iran

ObjectiveTo find out the phylogenetic background of hepatitis delta virus (HDV) samples isolated in Shahrekord, Iran.MethodsA total of 350 hepatitis B surface antigen (HBsAg) positive sera samples were found from blood donors and HBsAg positive patients in blood transfusion center and clinical laboratory in Shahrekord, Iran. HDV RNA was extracted using RNXPlus (CinnaGen, Iran). A total of 421 bp corresponding to hepatitis delta antigen have been isolated from HDV in Shahrekord, then were amplified in polymerase chain reaction system, sequenced for determining nucleotide sequence and compared with identified nucleotide sequences of these genes in other countries.ResutlsAmong 350 HBsAg positive samples, we could detect HCV RNA in only two samples. After sequencing, the nucleotide sequences had a variability of 1/7-3/0 for HD Ag gene. The greatest sequence similarity existed between Iranian HD Ag sequence and JF694493-Iran, U25667-China with a sequence similarity of 99.7% and the least relationship between Iranian HD Ag sequence and AF008420-USA with a similarity of 92.9%.ConclusionsIt is suggested that precise genotype of HDV circulating in the region can be determined by more expansive sampling from different parts of Chahar mahal and Bakhtiari province and neigh bouring provinces (Esfehan and Khoozestan).     

谷胱甘肽S转移酶的研究进展及其与肿瘤的相关性

药物代谢是细胞解毒机制的重要组成部分之一,其中主要涉及两种酶:Ⅰ和Ⅱ相药物代谢酶。谷胱甘肽S转移酶(GST)是一种重要的Ⅱ相药物代谢酶,可与Ⅰ相药物代谢酶一起催化药物形成高水溶性终产物。所以,GST能够抵御内源性和外源性亲电子物质的损害,并在抗肿瘤过程中发挥重要作用。编码GST的基因至少分布在7条染色体上,构成了一个超基因家族,编码具有GST活性的蛋白。GST有许多功能,传统观点认为,细胞中的GST可发挥防御内、外源性毒性化合物损害的作用。另外,GST在肿瘤细胞中高表达,可介导谷胱甘肽结合至大量抗癌药物底物上,导致肿瘤耐药的发生。     

乙型肝炎慢加急性肝衰竭前期的临床特征及预后评分模型的建立

目的探讨乙型肝炎相关慢加急性肝衰竭(HBV-ACLF)前期患者的临床特征,并建立相应的预后评分模型。方法利用HBV-ACLF中国诊断标准研究(COSSH-ACLF)队列,回顾性分析725例乙型肝炎相关慢加急性肝功能障碍(HBV-ACHD)患者的临床特征,采用多因素COX回归分析90 d预后的相关独立危险因素并建立预后评分模型,并利用内部500例和外部390例HBV-ACHD患者进行验证。结果在725例HBV-ACHD患者中,男性为主(76.8%),96.8%患者有肝硬化基础,并发症以腹水(66.5%)多见,器官衰竭以凝血功能衰竭(4.1%)为主,90 d病死率为9.2%。多因素COX回归分析得出,总胆红素(TBil)、白细胞计数(WBC)、碱性磷酸酶(ALP)是HBV-ACHD患者90 d病死率的最佳预测指标,并建立评分模型COSSH-ACHDs=0.75×ln(WBC)+0.57×ln(TBil)-0.94×ln(ALP)+10,其受试者工作特征曲线下面积(auROC)显著高于终末期肝病模型(MELD)、MELD-Na、CTP及CLIF-C ADs(P<0.05),500例内部随机选择组和390例外部验证组均验证了类似结果。结论HBV-ACHD患者是一组以肝硬化失代偿为主、合并少量器官衰竭的人群,其90 d病死率为9.2%,COSSH-ACHDs具有更高的预测HBV-ACHD患者90 d预后的效能,为临床早期诊治提供循证医学依据。     

Historical Comparison of Overall Survival after Hepatic Resection for Patients With Large and/or Multinodular Hepatocellular Carcinoma

The present study compared the efficacy of hepatic resection (HR) in patients with large hepatocellular carcinoma (HCC) and those with multinodular tumor and examined how that efficacy has changed over time in a large medical center.The intermediate stage of HCC comprises a highly heterogeneous patient population. Moreover, official guidelines have different views on the suitability of HR to treat such patients.A consecutive sample of 927 patients with preserved liver function and large and/or multinodular HCC who were treated by initial HR were divided into 3 groups: those with a single tumor ≥5 cm in diameter (n = 588), 2 to 3 tumors with a maximum diameter >3 cm (n = 225), or >3 tumors of any diameter (n = 114). Hospital mortality and overall survival (OS) in each group were compared for the years 2000 to 2007 and 2008 to 2013.Patients with >3 tumors showed the highest incidence of hospital mortality of all groups (P < 0.05). Kaplan–Meier survival analysis showed that OS varied across the 3 groups as follows: single tumor > 2 to 3 tumors > 3+ tumors (all P < 0.05). OS at 5 years ranged from 24% to 41% in all 3 groups for the period 2000 to 2007, and from 35% to 46% for the period 2008 to 2013. OS was significantly higher during the more recent 6-year period in the entire patient population, those with single tumor, and those with 3+ tumors (all P < 0.05). However, in patients with 2 to 3 tumors, OS was only slightly higher during the more recent 6-year period (P = 0.084).Prognosis can vary substantially for these 3 types of HCC. Patients with >3 tumors show the highest hospital mortality and lowest OS after HR. OS has been improving for all 3 types of HCC at our medical center as a consequence of improvements in surgical technique and perioperative management.     

2012年欧洲肝病学会及2010年美国肝病学会关于酒精性肝病指南的解读

<正>酒精性肝病(alcoholic liver disease,ALD)是世界范围内导致慢性肝病的主要原因。据美国国立卫生院酒精滥用与成瘾研究所(NIAAA)的报告显示,在美国肝硬化已成为导致死亡的第12大原因。近年来,在我国成人群体中ALD的发病率、占同期肝病住院患者的比例及酒精性肝硬化在肝硬化中的病因构成比不断上升,由此可见酒精所致的肝损伤已成为不可忽视的问题。2010年我国修订的ALD诊疗指南比较精炼,因此     

Type 1 diabetes is associated with significant changes of ACE and ACE2 expression in peripheral blood mononuclear cells

Background and aimsThe renin-angiotensin system (RAS), which is a key mediator of cardiovascular homeostasis, has two main axes. The classic one, including angiotensin-converting enzyme (ACE) and Angiotensin (Ang) II, promoting vasoconstriction, and the “alternative” one, including ACE2 and Ang1-7, with opposed actions to AngII. ACE2 has been identified as the main receptor of SARS-CoV2, whereby it enters the cells, leading to the downregulation of surface ACE2 and RAS tissue unbalance. Given that diabetes is associated with an increase in COVID-19 severity and death, we aimed at evaluating RAS expression in patients with type 1 diabetes (T1D).Methods and resultsThis is a case–control study comparing 39 T1D patients to 33 controls, with a median age of 29 and 32 years, and no comorbidities. ACE and ACE2 gene expression was assessed in peripheral blood mononuclear cells. T1D patients had higher ACE expression and circulating AngII, which were related to glucose levels. T1D patients had lower ACE2 expression. However, ACE2 expression was also related to the sex of participants, being higher in the female group. T1D women did not show the same increase of ACE2 expression that was seen in control women.ConclusionT1D promotes the increase of ACE, AngII, and ACE/ACE2, which might contribute to the higher cardiovascular risk, as well as to severe tissue injury induced by SARS-CoV2 in these patients. The ratio ACE/ACE2 does not differ between men and women with T1D, which might explain why CVD or COVID-19 do not show substantial gender differences in these patients.     

Advanced glycation end products,leukocyte telomere length,and mitochondrial DNA copy number in patients with coronary artery disease and alterations of glucose homeostasis: From the GENOCOR study

Background and aimAlterations of glucose homeostasis can increase advanced glycation end products (AGEs) that exacerbate vascular inflammatory disease and may increase vascular senescence and aging. This study examined the relationships between carboxymethyl-lysine (CML) and soluble receptor for AGEs (sRAGE) with leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn), as cell aging biomarkers, in patients with established coronary artery disease (CAD).Methods and resultsWe studied 459 patients with CAD further categorized as having normal glucose homeostasis (NG, n = 253), pre-diabetes (preT2D, n = 85), or diabetes (T2D, n = 121). All patients were followed up for the occurrence of major adverse cardiovascular events (MACEs). Plasma concentrations of sRAGE and CML were measured by ELISA. mtDNAcn and LTL were measured by qRT-PCR. CML levels were significantly higher in patients with preT2D (p < 0.007) or T2D (p < 0.003) compared with those with NG. mtDNAcn resulted lower in T2D vs preT2D (p = 0.04). At multivariate Cox proportional hazard analysis, short LTL (HR: 2.89; 95% CI: 1.11–10.1; p = 0.04) and high levels of sRAGE (HR: 2.20; 95% CI: 1.01–5.14; p = 0.04) were associated with an increased risk for MACEs in patients with preT2D and T2D, respectively. T2D patients with both short LTL and high sRAGE levels had the highest risk of MACEs (HR: 3.11; 95% CI: 1.11–9.92; p = 0.04).ConclusionsHigh levels of sRAGE and short LTL were associated with an increased risk of MACEs, especially in patients with diabetes, supporting the usefulness of both biomarkers of glycemic impairment and aging in predicting cardiovascular outcomes in patients with CAD.