血清miR-122-5p水平联合MSCT对肝癌的诊断价值

目的探讨血清miR-122-5p水平联合多层螺旋电子计算机断层扫描(MSCT)对肝癌的诊断价值。方法选取2016年1月至2019年1月我院80例肝癌患者纳入观察组,收集同期进行肝癌筛查的健康人群100例作为正常对照组,均进行MSCT检查,并检测血清miR-122-5p水平,绘制受试者工作特征曲线(ROC)分析血清miR-122-5p水平联合MSCT对肝癌的诊断价值。结果80例肝癌患者进行MSCT多期扫描共发现107个病灶,病灶大小为5~10mm;单个癌结节58例,2个癌结节17例,3个癌结节5例;病灶位于肝右叶50例,左叶27例,左、右叶3例;92个强化病灶中68个病灶呈明显或轻度较均匀强化,24个病灶呈不均匀强化,表现为肿瘤边缘环形强化、部分性强化、中心点状强化;MSCT检出率分别为动脉期88.79%(95/107)、门静脉期71.96%(77/107)、平衡期77.57%(83/107)、延迟期83.18%(89/107),综合多时相薄层扫描检出率为93.46%(100/107);肝癌患者血清中miR-122-5p水平低于正常对照组(P<0.05);ROC曲线分析显示,血清miR-122-5p、MSCT联合检查与肝癌诊断相关的AUC为0.884,高于miR-122-5p、MSCT单独检测的0.766、0.795(P<0.05)。结论血清miR-122-5p水平联合MSCT可有效提高肝癌的诊断价值。     

Phase I,multicenter, dose‐escalation study of avadomide in adult Japanese patients with advanced malignancies

Non‐Hodgkin lymphoma (NHL) treated with chemoimmunotherapy has limited efficacy in some patients, resulting in relapsed or refractory disease. Avadomide (CC‐122) is a novel cereblon‐binding agent that exhibits antilymphoma and immune‐modulation activities with a biological profile distinct from similar agents, such as lenalidomide. This phase I multicenter study evaluated avadomide in Japanese patients with advanced solid tumors or NHL. Fourteen patients with NHL and one with a solid tumor (esophageal carcinoma), were enrolled in four dose‐escalation cohorts using a 3 + 3 design. Primary endpoints included safety, dose‐limiting toxicities (DLT), maximum‐tolerated dose and/or recommended phase II dose (RP2D), and pharmacokinetics. Secondary endpoints included overall response rate (ORR) and duration of response. One patient with NHL experienced DLT, which included face edema, pharyngeal edema, and tumor flare (all grade 1) that led to a dose reduction. Eleven patients had grade ≥3 treatment‐emergent adverse events, most frequently decreased neutrophil count (33%) and decreased lymphocyte count (20%). The ORR in patients with NHL (n = 13) was 54%, including four complete and three partial responses. The best response for the solid tumor patient was progressive disease. Avadomide dose intensity was consistent across cohorts, and the 3‐mg dose given five consecutive days/week was established as the RP2D. This phase I study identified a tolerable dose of avadomide, with an acceptable toxicity profile and clinically meaningful efficacy in Japanese patients with previously treated NHL.     

Predicting risk in patients with acetaminophen overdose

Acetaminophen (APAP) overdose is a very common cause of drug overdose and acute liver failure in the US and Europe. Mechanism-based biomarkers of APAP toxicity have the potential to improve the clinical management of patients with large-dose ingestions of APAP. The current approach to the management of APAP toxicity is limited by imprecise and time-constrained risk assessments and late-stage markers of liver injury. A recent study of ‘low-risk’ APAP overdose patients who all received treatment with N-acetylcysteine found that cell death biomarkers were more sensitive than alanine aminotransferase (ALT) and APAP concentrations in predicting the development of acute liver injury. The data suggest a potential role for new biomarkers to identify ‘low-risk’ patients following APAP overdose. However, a practical and ethical consideration that complicates predictive biomarker research in this area is the clinical need to deliver antidote treatment within 10 h of APAP overdose. The treatment effect and time-dependent nature of N-acetylcysteine treatment must be considered in future ‘predictive’ toxicology studies of APAP-induced liver injury.     

Adipocytes-derived exosomal miR-122 promotes non-alcoholic fat liver disease progression via targeting Sirt1

AimsNonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that affects adipose function. This study aimed to explore the function of adipocytes-derived exosomal (ADEs) miR-122 in NAFLD.MethodsA high-fat and high-fructose diet-induced rat model and a palmitic acid (PA)-induced in vitro model were established. The RNA level of miR-122 and Sirt1 was measured using qRT-PCR. The protein levels of exosome biomarkers, and lipogenesis, inflammation and fibrosis biomarkers were determined by western blotting. Cell viability and apoptosis were assessed using cell counting kit-8 and flow cytometry, respectively. Serum alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride levels were measured. Liver tissue damage was assessed using haematoxylin and eosin staining. The interaction between miR-122 and Sirt1 3′UTR was assessed using a luciferase reporter gene assay.ResultsADEs exhibited abundant level of miR-122 and promoted lipogenesis, impaired hepatocyte survival, enhanced liver damage and increased serum lipid levels in vivo and in vitro. Inhibition of miR-122 in ADEs alleviated NAFLD progression, lipid and glucose metabolism, liver inflammation and fibrosis both in vivo and in vitro. miR-122 binds directly to the 3′UTR of Sirt1 to suppress its expression. Moreover, Sirt1 overexpression reversed the increase in cell apoptosis, glucose and lipid metabolism, liver inflammation and fibrosis induced by ADEs in vivo and in vitro.ConclusionsThe ADEs miR-122 promotes the progression of NAFLD via modulating Sirt1 signalling in vivo and in vitro. The ADEs miR-122 may be a promising diagnostic biomarker and therapeutic target for NAFLD.     

miR-103a-2、miR-122和vaspin在非酒精性脂肪性肝病合并HBV感染中的表达及意义

目的探讨微小RNA（miR）-103a-2、miR-122和丝氨酸蛋白酶抑制剂（vaspin）在非酒精性脂肪肝病（NAFLD）合并乙型肝炎病毒（HBV）感染中的表达及意义。 方法选择东营市胜利油田中心医院于2019年5月至2021年5月收治的NAFLD合并HBV感染患者97例作为观察组;选择同期收治的单纯NAFLD患者82例作为NAFLD组;另选择健康体检者80例作为正常组。所有研究对象均以实时荧光定量法（qRT-PCR）法检测miR-103a-2和miR-122相对表达量;采用酶联免疫吸附法（ELISA）测定血清vaspin水平;采用全自动生化分析仪测定肝功能［总胆红素（TBIL）、天门冬氨酸氨基转移酶（AST）和丙氨酸氨基转移酶（ALT）］水平。比较各组miR-103a-2和miR-122相对表达量,TBIL、AST和ALT水平变化。采用Spearson分析miR-103a-2、miR-122和vaspin与肝功能相关性;采用多因素Logistic回归分析NAFLD合并HBV感染影响因素。 结果观察组miR-103a-2和miR-122相对表达量及vaspin水平高于NAFLD组和正常组（P＜0.05）;NAFLD组miR-103a-2和miR-122相对表达量及vaspin水平高于正常组（P＜0.05）。观察组血清TBIL、AST和ALT水平高于NAFLD组和正常组（P＜0.05）;NAFLD组血清TBIL、AST和ALT水平高于正常组（P＜0.05）。采用Spearson相关性分析显示,miR-103a-2、miR-122和vaspin与呈TBIL、AST和ALT呈正相关（P＜0.05）。采用多因素Logistic回归分析显示,miR-103a-2、miR-122和vaspin为影响NAFLD合并HBV感染独立危险因素。 结论miR-103a-2、miR-122和vaspin在NAFLD合并HBV感染患者中高表达,且为影响NAFLD合并HBV感染独立危险因素。     

胆石症患者血清微小RNA -122、高迁移率族蛋白1和角蛋白-18水平及其临床意义*

目的 探讨胆石症患者血清微小RNA -122（miR-122）、高迁移率族蛋白1（HMGB 1）和半胱氨酸天冬氨酸蛋白酶裂解角蛋白-18（CCK-18）水平变化及其临床意义。方法 2015年1月~2018年2月我院收治的201例胆石症患者和健康体检者103例,比较两组人群血清miR-122、HMGB 1和CCK-18水平差异。采用Logistic回归分析影响单纯性胆石症进展为复杂性胆石症的相关因素。采用受试者工作特征曲线（ROC）下面积（AUC）分析血清指标诊断复杂性胆石症的效能。结果 胆石症患者血清miR-122、HMGB 1和CCK-18水平分别为4.7（0.9,14.3）、（2.5±0.7） ng/mL和（126.8±20.5）U/L,显著高于健康人【0.9（0.4,3.1）、（2.1±0.4） ng/mL和（101.4±18.7） U/L,均P<0.05】;97例单纯性胆石症组血清miR-122、HMGB 1和CCK-18分别为3.5（0.7,8.5）、（2.2±0.5）ng/mL和（112.4±19.4）U/L,显著低于104例复杂性胆石症组【分别为5.8（0.9,16.2）、（2.8±0.8） ng/mL和（140.2±23.5） U/L,均P<0.05】;单因素和多因素Logistic回归分析显示,肝硬化、腹腔积液、血清miR-122、HMGB 1和CCK-18为单纯性胆石症进展为复杂性胆石症的危险因素;血清miR-122、HMGB 1和CCK-18水平三者联合检测诊断复杂性胆石症的AUC为0.819（0.758~0.962）,显著高于miR-122【0.724（0.657~0.815）】、HMGB 1【0.701（0.633~0.804）或CCK-18【0.767（0.702~0.873）】单指标检测。结论 对血清miR-122、HMGB 1和CCK-18水平升高的胆石症患者,应想到复杂性胆石症的可能,而给予更仔细的检查和特别处理。     

hsa-mir-520真核表达载体的构建及对E-钙粘蛋白表达的影响

目的 构建hsa-mir-520真核表达载体,并转染大肠癌细胞SW-480细胞,检测细胞中E-钙粘蛋白表达情况.方法 依据miRBase数据库中hsa-mir-520序列,设计并合成寡核苷酸片段,构建hsa-mir-520表达载体和对照载体.采用脂质体转染方法分别将mir-520表达载体、及对照质粒转染大肠癌细胞SW-480细胞株.采用酶切、测序检测载体构建;Western blot检测E-钙粘蛋白的表达.结果 酶切和测序表明hsa-mir-520真核表达载体构建成功.Western blot结果显示与转染对照质粒和未转染的细胞相比,转染了hsa-mir-520重组质粒的细胞中E-cadherin蛋白的表达明显增加(P<0.01),密度扫描半定量分析显示E-cadherin蛋白的表达增加了大约40%.结论 成功构建了hsa-mir-520和对照的真核表达载体,hsa-mir-520质粒转染大肠癌细胞SW-480后可增加E-钙粘蛋白的表达.