BACKGROUND Long noncoding RNAs (lncRNAs) are closely associated with the initiation, progression, metastasis, and recurrence of hepatocellular carcinoma (HCC). They could therefore serve as markers for the early diagnosis and for the prognosis of HCC patients. METHODS This was an observational prospective cohort study. A total of 101 participants were included, comprising patients with HCC (n = 61), liver cirrhosis (LC) (n = 20), or healthy controls (HC) (n = 20). The baseline characteristics of participants in each group were compared. Serum levels of the lncRNAs HOTAIR, BRM and ICR were determined in each group by reverse transcription and quantitative real-time polymerase chain reaction (qRT-PCR). Correlations between the serum levels of the three lncRNAs and multiple clinical parameters were analysed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic potential for HCC of each lncRNA individually, or in combination with AFP. Multivariate Cox regression analysis was used to evaluate the accuracy of these lncRNAs for predicting the outcome and survival of HCC patients. RESULTS The serum levels of HOTAIR, BRM and ICR were significantly higher in HCC patients compared to LC patients and healthy subjects. The HOTAIR level was positively correlated to tumour-node metastasis (TNM), Barcelona Clinic Liver Cancer (BCLC) stage, extrahepatic metastasis, vascular invasion, portal vein tumour thrombus (PVTT), and tumour size. The BRM level was positively associated with TNM stage, BCLC stage, vascular invasion, PVTT, and tumour size, while the ICR level was positively correlated with PVTT. A combination of the three lncRNAs and AFP showed the highest diagnostic accuracy for HCC, with an AUC of 0.998, sensitivity of 98.4%, and specificity of 100.0%. This combination showed a better diagnostic accuracy than the individual lncRNAs or AFP alone. Serum levels of the HOTAIR and ICR lncRNAs decreased significantly following surgery. CONCLUSIONS Serum levels of the HOTAIR, BRM and ICR lncRNAs are potential prognostic markers for HCC. Upregulation of HOTAIR, BRM and ICR may facilitate early diagnosis and indicate poor prognosis for HCC. These lncRNAs could potentially serve as therapeutic targets for HCC. Combination of the three lncRNAs with AFP may increase the diagnostic accuracy for HCC. Further studies in larger cohorts of patients are needed to validate these findings.
BACKGROUNDLiver fibrosis is the early pathological manifestation of various chronic liver diseases (including schistosomiasis, alcoholic, viral, nonalcoholic, fatty liver, etc.), which can progress to cirrhosis and even liver cancer. Out of the 7.7 billion world population, approximately 2 billion individuals have evidence of hepatitis B virus (HBV) infection; of these, 350 to 400 million suffer from chronic HBV infection, accounting for about 5% of the global population. The global prevalence of hepatitis C is 3%. These figures indicate that liver fibrosis is quite common.METHODS98 patients with liver fibrosis were included in this study. The serum chitinase-3 Like Protein-1 (CHI3L1) level was measured by the double antibody Sandwich ELISA method.RESULTSSerum levels of CHI3L1 were significantly different between no-fibrosis and fibrosis groups (P < 0.01). There was a strong correlation between the levels of CHI3L1, elastometry, hyaluronan, CIV (P < 0.01) and age and sex, TBIL, DBIL, ALB, AST, ALT, GGT, ALP, PLT, LN, PIINP, FIB-4, and APRI (P < 0.05). The expression of CHI3L1 was different from fibrosis grades S1, S3, and S4 (P < 0.05, P < 0.001). The expression of CHI3L1 was significantly different between F1 and F4 (P < 0.05). Serum CHI3L1 expression level can be a valuable metric for diagnosing liver fibrosis, with an AUC value of 0.812. Out of the 98 patients who had undergone liver puncture, 79 patients (30.38%) had ALT ≤ 2ULN.CONCLUSIONSThe expression level of serum CHI3L1 was significantly higher in patients with liver fibrosis than that in patients without liver fibrosis. The expression levels of serum CHI3L1 were different in different grades of liver fibrosis and increased with the severity of liver fibrosis. Serum CHI3L1 can distinguish early stage (S1) of liver fibrosis from late stage (S3-4) of liver fibrosis. Serum CHI3L1 combined with HA is even more effective in the diagnosis of S2-4 hepatic fibrosis. The diagnostic efficacy of serum CHI3L1 in patients with ALT ≤ 2ULN was better than that of the other non-invasive diagnostic models.
目的:探讨lncRNA HOTAIR在肝癌患者血清中的表达及其临床诊断意义.方法:采用qRT-PCR法检测61例原发性肝癌(PLC)患者、20例肝硬化患者及20例健康体检者的血清lncRNA HOTAIR表达水平,并分析其与患者临床病理特征关系及肝癌诊断价值.结果:PLC患者血清lncRNA HOTAIR表达量高于肝硬化组和健康对照组(P<0.05).PLC患者血清lncRNA HOTAIR表达量与TNM分期、Child-Pugh肝功能分级标准、肝外转移、血管侵犯、癌栓形成、肿瘤大小有关(P<0.05).ROC分析结果显示血清lncRNA HOTAIR表达量诊断肝癌的AUC、敏感度和特异性分别为0.991、95.7%、95.0%;预测TNM分期的AUC、敏感度和特异性分别为0.708、78.3%、60.5%(P<0.001).结论:PLC患者血清lncRNA HOTAIR明显高于肝硬化组与健康组,lncRNA HOTAIR高表达PLC患者恶性程度高、肿瘤直径大、肝功能差,且lncRNA HOTAIR高表达与PLC的肝外转移、血管侵犯、癌栓形成有关,可能参与了肝癌的发生发展.血清lncRNA HOTAIR诊断PLC灵敏度、特异度、准确度高,对PLC临床诊断有一定价值.
新型冠状病毒肺炎(COVID-19)是由新型冠状病毒感染所致,以发热、乏力、干咳为主要临床表现,传染性强,病因为感受疫疠之气,属于中医"疫病"的范畴,病位在肺脾,发病多与"寒、湿、热、毒、瘀"等多因素有关,但疾病不同时期的侧重点不同,故需分期而论,分证而治.本文将探讨中医药对杭州市新型冠状病毒肺炎患者的分期辨证治疗,充分挖掘中医药对新型冠状病毒肺炎的治疗潜力.
目的:探讨益气化瘀法调控Nrf2-Keap1-Are抗氧化应激通路对气虚血瘀型肝纤维化大鼠作用机制.方法:将30只SD大鼠,根据随机数字表法分正常组、模型组、治疗组,每组10只,除正常组外其余两组大鼠以CCl4和游泳试验行气虚血瘀型肝纤维化造模.从实验第7周开始,模型组和正常组大鼠以2 ml生理盐水灌胃,1次/d;治疗组大鼠以0.5g/kg剂量的扶正化瘀胶囊生理盐水溶液灌胃,1次/d.均连续灌胃4周.之后处死大鼠分别测定肝重、肝湿重;采用RT-PCR法检测α-SMA、Nrf2、Keap1、β-actinmRNA表达水平,用Western blot法检测α-SMA、LC3Ⅱ、P62、Nrf2、Nqo1、GAPDH蛋白表达量.结果:模型组大鼠肝纤维化Ishak评分高于正常组和治疗组(P<0.01);模型组大鼠α-SMA mRNA表达最高,治疗组大鼠其表达量显著下降(P<0.05);模型组大鼠Nrf2、KeaP1 mRNA表达最低,治疗组大鼠其表达量显著升高(P<0.05);α-SMA、LC3Ⅱ蛋白表达在模型组最高,在治疗组则显著下降(P<0.05);而P62、Nrf2、Nqo1蛋白表达在模型组最低,在治疗组则显著升高(P<0.05).结论:气虚血瘀型肝纤维化大鼠LC3Ⅱ蛋白可下调P62蛋白表达,进而抑制Nrf2-Keap1-Are抗氧化应激通路的激活,加重肝纤维化进展,通过具有益气扶正、活血化瘀作用的扶正化瘀胶囊治疗,可逆转上述过程.