肝癌患者因食欲降低、进食减少导致不同程度的营养不良,引发厌食症,甚至恶病质,严重影响患者生存质量。食欲评估是降低营养风险的基础,医护人员可通过食欲症状的评估调整患者饮食及营养指导措施,以改善患者营养状态,提高生存质量。该文对食欲的评估工具、方法及干预在肝癌营养不良患者中的应用现状进行阐述,为肝癌患者的食欲干预提供科学依据。

Hepatocellular carcinoma patients suffer from different degrees of malnutrition due to decreased appetite and eating,which triggers anorexia and even cachexia,seriously affecting the quality of patient survival．Appetite assessment is the basis for reducing nutritional risk,and healthcare professionals can adjust patients’ diet and nutritional guidance measures through the assessment of appetite symptoms in order to improve patients’ nutritional status and survival quality．In this paper,the current status of the assessment tools,methods and interventions of appetite in malnutrition patients with hepatocellular carcinoma are described to provide a scientific basis for appetite interventions．

目的 探究长链非编码RNA SNHG12在乙肝病毒X蛋白(HBx)诱导肝癌发生过程中的作用。方法 把课题组构建的肝前体细胞14-19、EGFP-14-19、HBx-EGFP-14-19通过小鼠肝门静脉注射到体内;采用 qRT-PCR、Western blot 方法检测30 d,90 d,180 d,360 d小鼠肝脏组织及细胞模型中HBx、SNHG12以及下游调节基因的mRNA和蛋白表达情况;使用si-SNHG12干扰其表达,并通过CCK-8、划痕实验、transwell实验、流式细胞术观察其对体外表型影响;检测SNHG12及下游的 mRNA 和蛋白表达;HE染色观察小鼠肝组织切片。结果 qRT-PCR结果表明SNHG12、Notch1、Hes1在HBx-EGFP-14-19细胞及各时间段的小鼠肝组织中均上调(F=48.808,P<0.000 1;F=13.322,P<0.000 1);Western blot结果显示在HBx过表达细胞及动物模型中,受HBx诱导SNHG12表达升高后Notch1信号通路被激活,促凋亡因子Bax下调,抗凋亡因子Bcl-2上调,细胞周期因子CDK2和Cyclin E上调;抑制SNHG12表达后,qRT-PCR、Western blot实验结果显示SNHG12(t=22.746,P<0.000 1)及其上述基因表达均扭转,CCK-8实验显示细胞增殖受到明显抑制,流式细胞术检测显示细胞凋亡增多,划痕及transwell实验表明细胞迁移及侵袭减弱。结论 HBx通过上调SNHG12诱导Notch1表达,导致细胞增殖、周期和凋亡异常,从而促进肝癌的发生。

Objective In order to explore the role of long non-coding RNA SNHG12 in hepatitis B virus X protein (HBx) induced hepatocarcinogenesis. Methods The liver precursor cells 14-19, EGFP-14-19 and HBx-EGFP-14-19 constructed by the research group was injected into the body through the hepatic portal vein of KM mice; qRT-PCR and Western blot were used to detect the mRNA and protein expression of HBx, SNHG12 and downstream regulatory genes in liver tissues of 30 d, 90 d, 180 d and 360 d mice and cell models. Si-SNHG12 was used to interfere with SNHG12 expression in vitro, the mRNA and protein expression of SNHG12 and downstream genes were detected, and its effect on phenotype in vitro was observed by CCK-8, flow cytometry, scratch test and transwell test. HE staining was used to observe the liver sections of mice. Results qRT-PCR showed that SNHG12, Notch1 and Hes1 were up-regulated in HBx overexpression cells and mouse liver tissue at each time point (F=48.808,P<0.000 1;F=13.322,P<0.000 1); the results of Western blot showed that in HBx over-expressing cells and animal models, the expression of SNHG12 was increased induced by HBx, resulting in the activation of Notch1 signal pathway, the down regulation of pro-apoptotic factor Bax, anti-apoptotic factor Bcl-2, and the up-regulation of cell cycle factors CDK2, cyclin E. After inhibiting the expression of SNHG12, the results of qRT-PCR and Western blot showed that SNHG12 (t=22.746,P<0.000 1) and the above genes were inhibited; CCK-8 experiment showed that cell proliferation was significantly inhibited, flow cytometry showed that cell apoptosis increased, scratch experiment and transwell experiment showed that cell migration and invasion decreased. Conclusions HBx induced Notch1 expression by up regulating SNHG12, resulting in abnormal cell proliferation, cycle and apoptosis, so as to promote the occurrence of liver cancer.

目的 分析CT+MRI在原发性肝癌诊断与介入治疗预后评估中的临床意义。方法 选定本院2019年1月—2021年1月住院治疗的150例原发性肝癌患者,入院后均接受介入治疗,分别予以CT、MRI检查,将手术病理检查结果作为本次研究的金标准,比较CT、MRI、CT+MRI诊断效能,Kappa检验CT、MRI、CT+MRI与金标准的一致性,比较CT、MRI、CT+MRI介入术后病灶检出率。结果 CT+MRI诊断准确率(98.67%)、特异度(75.00%)、灵敏度(99.32%)均高于CT(86.00%、25.00%、87.67%)、MRI(90.67%、91.78%、50.00%),P＜0.05(差异均有统计学意义),CT+MRI与金标准的一致性较好(Kappa值为0.779),CT、MRI与金标准的一致性一般(Kappa值为0.527、0.596)。CT+MRI介入术后病灶总检出率(12.00%)高于CT(2.00%)、MRI(4.00%),P＜0.05(差异有统计学意义)。结论 CT+MRI可提高原发性肝癌患者介入术后病灶检出率,弥补了单一CT、MRI检查的不足。

Objective To evaluate the clinical significance of CT + MRI scans in diagnosis of primary liver cancer and prognosis evaluation after interventional therapy. Methods A total of 150 cases of patients with primary liver cancer admitted to our hospital from January 2019 to January 2021 were selected. They all received interventional treatment, and were examined by CT and MRI. The results of pathological examination were taken as the gold standard in this study to compare the diagnostic efficacy of CT, MRI and CT+MRI.Kappa value was used to compare the consistency of CT, MRI, CT+MRI scans with gold standard, and compared the detection rate of lesions after CT, MRI and CT+MRI interventional surgery. Results The diagnostic accuracy (98.67%), specificity (75.00%) and sensitivity (99.32%) of CT + MRI scans were higher than those of CT (86.00%, 25.00%, 87.67%) and MRI scans (90.67%, 91.78%, 50.00%),P<0.05 (which differences were statistically significant). The consistency of CT + MRI scans with gold standard was good (kappa value was 0.779), but the consistency of CT/MRI scans with gold standard were not satisfying (kappa value were 0.527, 0.596). The total detection rate of lesions after CT + MRI interventional surgery (12.00%) was higher than that of CT (2.00%) and MRI (4.00%, which P<0.05). Conclusion CT + MRI scans can improve the detection rate of lesions in patients with primary liver cancer after interventional therapy, and make up for the deficiency of only CT or MRI scans.

目的 探讨组蛋白去乙酰化酶抑制剂曲古霉素对肝癌细胞增殖凋亡是否存在影响,及该抑制作用是否与自噬相关。方法 采用MTT法检测不同浓度曲古霉素作用于肝癌HepG2细胞24 h、48 h、72 h以后肝癌细胞的增殖能力;使用流式细胞术检测不同浓度曲古霉素对HepG2肝癌细胞周期及凋亡的影响;蛋白印迹法(Western blot, WB)检测不同浓度曲古霉素对肝癌HepG2细胞中Beclin1和Bcl-2蛋白的表达;实时荧光定量 PCR(Real-time PCR, RT-PCR)检测不同浓度曲古霉素对肝癌HepG2细胞中Beclin1和Bcl-2 mRNA的表达。结果 曲古霉素对肝癌HepG2细胞具有增殖抑制作用,与对照组相比较,其差异有统计学意义(P＜0.05);通过流式细胞术检测结果显示,曲古霉素作用于肝癌HepG2细胞后,随着浓度的增加,细胞凋亡率显著上升,与对照组相比,差异有统计学意义(P＜0.05);RT-PCR及WB实验观察到,Beclin1蛋白和mMRA的表达随着曲古霉素浓度的增加而逐渐升高,Bcl-2蛋白和mMRA的表达随着曲古霉素作用浓度的增加而逐渐降低,且与对照组相比,其差异均有统计学意义(P＜0.05)。结论 曲古霉素能抑制肝癌细胞的增殖,而且这种作用机制与诱导肝癌细胞凋亡和自噬作用有相关性。

Objective To investigate whether histone deacetylase inhibitor hachimycin has an effect on the proliferation and apoptosis of hepatocellular carcinoma cells and whether the inhibition is related to autophagy. Methods MTT assay was used to detect the proliferation ability of HepG2 cells treated with hachimycin of different concentrations for 24 h, 48 h and 72 h.Flow cytometry was used to detect the effects of different concentrations of hachimycin on HepG2 hepatoma cell cycle and apoptosis.Western blot (WB) assay was used to detect Beclin1 and Bcl-2 expressions in hepatocellular carcinoma HepG2 cells under different hachimycin concentrations.Beclin1 and Bcl-2 mRNA expressions under different hachimycin concentrations in hepatocellular carcinoma HepG2 cells were detected by RT-PCR. Results Hachimycin inhibited the proliferation of HepG2 cells, compared with the control group, the difference was statistically significant (P<0.05). Flow cytometry results showed that the apoptosis rate of hepatocellular carcinoma HepG2 cells was significantly increased with the increase of hachimycin concentration, compared with the control group, the difference was statistically significant (P<0.05). RT-PCR and WB results showed that Beclin1 protein and mMRA expression gradually increased with the increase of hachimycin concentration, while Bcl-2 protein and mMRA expression gradually decreased, compared with the control group, the differences were statistically significant (P<0.05). Conclusion Hachimycin could inhibit the proliferation of hepatocellular carcinoma cells, and its mechanism was related to the induction of apoptosis and autophagy.

目的 检测外周血循环肿瘤细胞(circulating tumor cell, CTC)在原发性肝癌患者中的表达情况,并探讨CTC动态变化及其相对于甲胎蛋白(Alpha fetoprotein AFP)对原发性癌患者术后复发转移的预测作用。方法 收集原发性肝癌患者134例,肝脏良性病变患者72例,检测外周血 CTC 数目,同时检测AFP的表达水平,分析 CTC 与 AFP 的相关性。然后在134名原发性肝癌患者中筛选出成功行肝癌根治术的患者,共86例,检测这86名患者术前、术后外周血CTC和AFP,分析CTC和AFP对原发性肝癌术后复发转移的评估价值。结果 原发性肝癌患者外周血CTC阳性率高于肝脏良性病变患者,差异有统计学意义(P＜0.05);原发性肝癌患者CTC水平与AFP水平、淋巴结转移、肿瘤结节多少有关,与年龄、性别、肿瘤直径、分化程度、肝硬化有无、TNM分期无关;原发性肝癌患者CTC和AFP生存分析显示,原发性肝癌根治术后早期复发转移与CTC和AFP密切相关;CTC较阳性对术后复发转移具有更好的诊断价值,二者联合对复发转移预测价值最高。结论 CTC可以做为一个比传统肿瘤标志物更好的对原发性肝癌术后复发转移进行监测的指标,与肿瘤标志物联合检测预测价值更高。

Objective To detect the expression of peripheral blood circulating tumor cells CTC in patients with primary liver cancer and to explore the dynamic changes of CTC and its predictive effect on postoperative recurrence and metastasis of primary cancer. Methods The number of CTC in peripheral blood was measured in 134 patients with primary liver cancer and 72 patients with benign liver disease, the expression of AFP was detected, and the correlation between CTC and AFP was analyzed. Then 86 patients with primary liver cancer were selected from 134 patients with primary liver cancer who underwent radical hepatectomy. The values of CTC and AFP in evaluating recurrence and metastasis of primary liver cancer before and after operation were analyzed by CTC and AFP, in peripheral blood of these 86 patients. Results The positive rates of CTC in peripheral blood of patients with primary liver cancer were higher than that of patients with benign liver disease(P< 0.05). The levels of CTC in patients with primary liver cancer were related to AFP level, lymph node metastasis and the number of tumor nodules, but not to age, sex, tumor diameter, differentiation degree, liver cirrhosis and TNM stage. The survival analysis of CTC and AFP in patients with primary liver cancer showed that the early recurrence and metastasis of primary liver cancer after radical resection were closely related to the positive rate of CTC and AFP, and the positive rate of CTC was more effective than that of AFP positive in the diagnosis of recurrence and metastasis after operation, and the combination of the two had the highest predictive value for recurrence and metastasis. Conclusion CTC may be used as a better index to monitor postoperative recurrence and metastasis of primary liver cancer than traditional tumor markers. The combined detection prediction value of tumor markers is higher.

目的 评价贝伐单抗联合肝动脉化疗栓塞治疗原发性肝癌的疗效及不良反应。方法 2名评价员通过独立地检索中英文数据库,纳入随机对照研究,其中治疗组为肝动脉灌注贝伐单抗联合肝动脉化疗栓塞组、对照组为单独肝动脉化疗栓塞组,并通过Jadad量表对纳入文献质量进行评分,最后采用Review Manager 5.2软件进行Meta分析。结果 纳入6篇文献,466例病例。结果显示:在疗效方面,治疗组的3、6个月疾病有效率及疾病控制率,12个月的生存率均高于对照组且差异有统计学意义(P<0.05);在安全性方面,两组间关于发热、转氨酶升高、恶心、黑便的发生率之间的比较无统计学意义(P＞0.05)。结论 肝动脉灌注贝伐单抗联合肝动脉化疗栓塞治疗原发性肝癌与单独肝动脉化疗栓塞比较,能有效提高肝癌患者近期及远期疗效,且并不增加不良反应发生率。

Objective To evaluate the efficacy and side effects of bevacizumab combined with thanscatheter artierial chemoembolzation in the treatment of primary liver cancer. Methods Two reviewers collected data about clinical trials that the combination of bevacizumab and thanscatheter artierial chemoembolzation for treatment of primary liver cancer from data bases. Jadad Score and Review Manager 5.2 software were respectively used to assess the quality of included studies and analyze the obtained data. Results Six randomized controlled trials involving 466 patients were included in this paper. The results of the meta-analysis showed that compared with thanscatheter artierial chemoembolzation group alone, bevacizumab combined with thanscatheter artierial chemoembolzation improved the response rate and disease control rate, prolonged 12 month survival rate (P<0.05). As for side effects, there were no statistically different of those about fever, level of transaminase, nausea and melena between two groups(P>0.05). Conclusion Compared with simple thanscatheter artierial chemoembolzation group, and Bevacizumab combined with thanscatheter artierial chemoembolzation group, the later may improve short-term and long-term effects, and side effects were under control.

目的 探讨超声引导下射频消融术治疗肝癌的资料,评价其术后局部复发的影响因素,为临床应用提供参考依据。方法 回顾性分析2010年7月—2012年7月我院进行超声引导下射频消融治疗肝癌80例患者的临床资料,通过统计学软件,明确射频消融术的疗效,通过单因素分析中的χ²检验和logistic线性回归分析等方法分析射频消融治疗肝癌局部复发的主要危险因素。结果 80例肝癌患者行超声引导下射频消融术治疗的次数共为94次,12例肝癌患者接受RFA治疗的次数≥2次,94次肝癌射频消融术处理病灶共为101个,完全消融共为68例(85.0%),不完全消融12例(15.0%);所研究病例瘤体个数按≤3 cm、3～5 cm、>5 cm分组总数分别为55、34、12,其完全消融率分别为89.09%、79.41%、66.67%;运用多因素统计分析,结果显示肝硬化、肝炎史以及血管癌栓形成是影响肝癌患者射频消融术后局部复发的独立因素。结论 RFA治疗肝癌是一种疗效满意的局部微创治疗手段,肝硬化、肝炎史、血管癌栓形成是影响肝癌患者术后局部复发的独立高危因素。

Objective To provide reference for clinical application, we investigated the data of ultrasound-guided radiofrequency ablation RFA in the treatment of hepatocellular carcinoma and evaluated the influencing factors of local recurrence after operation. Methods The clinical data of 80 patients with hepatocellular carcinoma treated with ultrasound-guided radiofrequency ablation from July 2010 to July 2012 in our hospital were analyzed retrospectively. The efficacy of radiofrequency ablation was determined by statistical software analysis. We analyzed the main risk factors of local recurrence of hepatocellular carcinoma treated with radiofrequency ablation by χ² test and logistic linear regression analysis in univariate analysis. Results The frequency of ultrasound-guided radiofrequency ablation in 80 patients with hepatocellular carcinoma was 94 times and a total of 101 lesions were treated. Among them, 12 patients with hepatocellular carcinoma were treated with RFA more than 2 times. In 80 patients with hepatocellular carcinoma treated with RFA, 68 cases (85.0%)underwent complete ablation and 12 cases (15.0%)underwent incomplete ablation. The treated lesions were divided into 55, 34 and 12 lesions respectively, according to the size of≤ 3cm, 3 ≤ 5cm,>5cm. And the complete ablation rates were 89.09%, 79.41% and 66.67% respectively. Multivariate statistical analysis showed that liver cirrhosis, hepatitis history and vascular tumor thrombus formation were independent factors for the local recurrence of patients with hepatocellular carcinoma after radiofrequency ablation. Conclusion RFA treatment of hepatocellular carcinoma is a local minimally invasive treatment with satisfactory efficacy. Cirrhosis, hepatitis history and vascular tumor thrombosis are independent high risk factors for the local recurrence of patients with hepatocellular carcinoma.

目的 分析促红细胞生成素（EPO）及促红细胞生成素受体（EPOR）在肝细胞癌（NCC）以及正常组织中的表达规律,以及它们和肝细胞癌微血管密度（MVD）之间的关系。方法 选取我院手术切除的肝细胞肝癌的标本30例,取肿瘤边缘2.0 cm的肝组织作为对照,同时取正常肝脏组织10例做为阴性对照。利用酶联免疫吸附实验（ELISA）检测各组织中EPO及EPOR表达水平,利用免疫组织化学方法染色检测微血管密度（MVD）。对比癌组织和癌旁组织EPO、EPOR及MVD差异,分析NCC中EPO、EPOR、MVD与肿瘤病理特征的关系,分析EPO、EPOR表达水平与MVD之间的关系。结果 HCC组织中,EPR、EPOR、MVD均高于癌旁组织和正常组织,差异有统计学意义（P<0.001）,EPR、EPOR、MVD在癌旁组织和正常组织中,差异无统计学意义（P>0.05）。肿瘤大小>5 cm、存在包膜侵犯、存在远处转移以及高中分化的HCC中,EPR、EPOR、MVD水平高于肿瘤大小≤5 cm、无包膜侵犯、无远处转移以及低分化的水平,差异有统计学意义（P<0.05）。Person相关分析结果显示,EPO表达水平与MVD的相关系数r=0.651（P<0.001）,EPOR表达水平与MVD的相关系数r=0.620（P<0.001）。结论 EPO、EPOR、MVD在HCC中呈现高水平,且与肿瘤大小、局部侵犯、远处转移及分化程度有关,其机制可能与EPO、EPOR增加MVD有关。

Objective To analyze the expression of erythropoietin （EPO） and erythropoietin receptor （EPOR） in hepatocellular carcinoma （NCC） and normal tissues,and their relationship with hepatocyte microvessel density （MVD）. Methods Thirty specimens of hepatocellular carcinoma hepatectomy were selected from our hospital. The liver tissue at the edge of the tumor was taken as a control,and 10 cases of normal liver tissue were used as a negative control. The expression levels of EPO and EPOR in each tissues were detected by enzyme-linked immunosorbent assay （ELISA）,and microvessel density （MVD） was detected by immunohistochemistry. The differences of EPO,EPOR and MVD between each tissues were compared. The relationship between EPO,EPOR,MVD and tumor pathological features in NCC was analyzed. The relationship between EPO and EPOR expression levels and MVD was analyzed. Results In HCC tissues,EPR,EPOR and MVD were higher than those in adjacent tissues and normal tissues. The difference was statistical difference （P<0.001）. EPR,EPOR and MVD were not statistically significant in adjacent tissues and normal tissues. P>0.05）. The levels of EPR,EPOR,and MVD in tumors with tumor size >5 cm,invasion of the capsule,distant metastasis,and high-differentiation were higher than those of tumor size ≤ 5 cm,no capsule invasion,no distant metastasis,and poor differentiation. The difference was statistical difference （P < 0.05）. Person correlation analysis showed that the correlation coefficient between EPO expression level and MVD was r=0.651 （P<0.001）,and the correlation coefficient between EPOR expression level and MVD was r=0.620 （P<0.001）. Conclusion EPO,EPOR and MVD are highly expressed in HCC,and are related to tumor size,local invasion,distant metastasis and differentiation. The mechanism may be related to EPO and EPOR increasing MVD.

目的 观察小剂量阿帕替尼联合经肝动脉化疗栓塞术(TACE)对晚期肝癌的疗效。方法 选择2016年1月1日—2017年12月31日在我院住院治疗的晚期肝癌患者38例,将其随机分为对照组和观察组,每组19例,对照组给予TACE治疗,观察组在TACE治疗的基础上联合口服阿帕替尼(250 mg/d)。随访两组患者的存活状态,Kaplan-Meier 法计算中位生存期,并绘制生存曲线,采用log-rank法比较两组患者生存曲线的差异。结果 对照组和观察组中位生存期分别为4.3月、5.8月,两组生存曲线比较有差异(χ²=4.691,P=0.043)。结论 相比于单纯TACE治疗,小剂量阿帕替尼联合TACE方案可以延长晚期肝癌患者的生存期。

肝细胞肝癌(HCC)是世界上最常见的肿瘤之一,其病因及确切的分子机制尚不完全清楚,目前认为其发病是多因素、多步骤的复杂过程,且预后较差。miRNAs在调控细胞的周期变化中起到重要的作用,它具有较高的组织特异性,在肿瘤发生中起到关键作用,从而有潜力作为肝癌的诊断和分类的新生物标志物,以及预测患者预后的工具。本文就近年来miRNAs在肝细胞肝癌方面的研究进展做一综述。