磁共振波谱在5-氟尿嘧啶热化疗治疗兔肝VX2移植瘤效果评价中的应用

目的 比较兔肝VX2移植瘤经介入性热化疗（ITC）治疗前后1H-MRS主要代谢物的变化,并与细胞凋亡指数（AI）进行相关性分析.方法 选取新西兰大白兔20只,采用组织块种植的方法成功制成兔VX2肝癌模型,10d后,待肿瘤直径≥10 mm时,分别于治疗前1天、治疗后第14天行常规磁共振成像（MRI）及磁共振波谱（MRS）扫描.使用Philips 1.5T MR成像仪,选取病灶不同感兴趣区（ROI）,分别测量治疗前、后不同ROI的观察肿瘤治疗前后的胆碱（Cho）峰值与脂质（Lip）峰值及两者比值的变化,免疫组织化学法及HE染色检测肿瘤细胞AI,并与MRS结果进行对照,分析不同ROI的主要代谢物变化规律.结果 在成功获得的1H-MRS波谱图中多数可见到6个主要的代谢物波峰,治疗前Cho峰、Lip峰均升高;治疗后Cho峰值较治疗前下降、Lip峰值则进一步升高,Cho/Lip比值降低,两两比较差异均有统计学意义（P＜0.05）;治疗后Cho/Lip峰值比与AI值呈负相关（r=-0.56,P=0.02）.结论 兔肝VX2移植瘤不同ROI的1H-MRS主要代谢物的变化情况与肿瘤细胞AI表达程度及范围一致;1H-MRS能反映VX2移植瘤ITC治疗前后肿瘤细胞凋亡和能量代谢变化情况.     

肝细胞癌经导管动脉化疗栓塞前后磁共振波谱研究

背景与目的:肝脏活体氢质子磁共振波谱(1H proton magnetic resonance spectroscopy,1HMRS)尚处于实验阶段,用1HMRS观察肝癌经导管动脉化疗栓塞(transcatheter arterial chemoembolization,TACE)疗效报道少。本研究旨在用1HMRS评价肝细胞癌TACE术前后代谢物的改变。方法:对25例肝细胞癌患者,应用GESignaHorizonLX、1.5T磁共振扫描仪,分别在TACE术前后进行MRS检查,所得的数据经机器自带的分析软件FuncTool2.5.36处理,得出术前术后Cho/Lip比值、Glu/Lip比值、Glx/Lip比值,并进行统计学分析。结果:成功实施MRS有21例,Cho/Lip比值TACE术前为0.21±0.08,术后为0.10±0.08;Glu/Lip比值TACE术前为0.11±0.05,术后为0.07±0.07;Glx/Lip比值术前为0.28±0.10,术后为0.18±0.12。术前术后比较,均P<0.05。结论:MRS可观查到肝癌TACE术前后的代谢物改变。     

脑胶质瘤氢质子磁共振波谱代谢物与Ki-67抗原的相关性及其应用价值

摘 要：［目的］ 探讨胶质瘤氢质子磁共振波谱（1-H magnetic resonance spectroscopy,1H-MRS）所示代谢物值与Ki-67抗原的相关性及其应用价值。［方法］ 回顾性分析83例术前行1H-MRS检查、术后病理学结果为脑胶质瘤的患者资料,对比分析胶质瘤实质部位主要代谢物N-乙酰天门冬氨酸（NAA）、胆碱（Cho）、肌酸（Cr）及其比值（Cho/Cr、Cho/NAA、NAA/Cr）与Ki-67表达的相关性。［结果］ Cho/Cr、Cho/NAA比值与Ki-67表达呈正相关(r=0.257,P=0.019;r=0.329,P=0.002),NAA/Cr比值与Ki-67表达呈负相关(r=-0.206,P=0.049);Lip出现率与Ki-67表达呈正相关（r=0.304,P=0.005）。［结论］ 1H-MRS检查的各代谢物值与Ki-67表达关系密切,可有效反应脑胶质瘤的增殖活性,其中Cho/NAA比值的诊断价值最高。     

氢质子磁共振波谱（^1H-MRS）分析对放射性脑坏死与脑肿瘤复发的鉴别作用

目的：探讨氢质子磁共振波谱分析（^1H-MRS）对放射性脑坏死和脑肿瘤复发的鉴别作用。方法：选择35例经放射治疗后,在常规MRI图像上发现原肿瘤部位或周边有新的异常强化灶的脑恶性胶质瘤、脑转移瘤患者,其中3—4级胶质瘤18例,脑转移瘤17例。多体素^1H-MRS采用PRESS序列。研究指标包括N-乙酰门冬氨酸（NAA）、胆碱（Cho）及肌酐（Cr）。结果：NAA、Cho及Cr下降或消失,NAAVCr比值与Cho／Cr比值均下降;脑肿瘤复发Cho上升,NAA明显下降。脑肿瘤复发和放射性脑坏死之间,Cho／Cr、Cho／NAA有统计学差异（P〈0．05）,NAAVCr无统计学差异（P〉0．05）。结论：^1H-MRS对脑肿瘤放射治疗后的脑坏死及脑肿瘤复发的评估和鉴别诊断有重要临床应用价值。     

1HMRS对脑转移瘤的诊断价值

目的：探讨氢质子磁共振波谱（proton magnetic resonance spectroscopy,1 H MRS）对脑转移瘤的诊断价值。方法：收集术后病理或临床证实脑转移瘤32例。所有患者MRS前均行MR平扫及增强扫描。3．0T MR多体素波谱（TE 144ms）扫描,分别于肿瘤实质、瘤周水肿及正常脑实质取感兴趣区（VOI）,测量代谢物浓度,计算Cho／Cr、NAA／Cr、Cho／NAA值,比较肿瘤实质与正常脑实质、瘤周水肿与正常脑实质代谢物比值的差异,采用配对t检验。观察肿瘤实质是否出现1．3ppm脂峰（Lip）及可流动脂质。结果：肿瘤实质与正常脑实质代谢物比较,Cho／Cr增高、NAA／Cr降低、Cho／NAA增高,差异有统计学意义（P均＜0．05）。瘤周水肿与正常脑实质代谢物比较,Cho／Cr略有增高,NAA／Cr 略有降低,差异无统计学意义（P均＞0．05）;Cho／NAA 增高,差异有统计学意义（P＜0．05）。32例中24例出现Lip,出现率75％,15例出现可流动脂质,出现率46．9％。结论：脑转移瘤的MRS具有一定特征,脂峰及可流动脂质的出现有助于脑转移瘤的诊断。     

磁共振波谱分析中胆碱对四肢软组织肿瘤的诊断价值

目的：探讨磁共振波谱（1H-MRS）分析中胆碱对四肢软组织肿瘤的诊断价值。方法： 回顾性分析82例经病理证实,四肢软组织实性病变的肿瘤患者资料,其中良性肿瘤39例,恶性肿瘤43例,病理诊断前均行常规磁共振（MRI）及1H-MRS检查,分别记录肿瘤区域代谢产物胆碱（Cho）、肌酸（Cr）的峰值积分,并计算出Cho与Cr的峰值积分比值（Cho/Cr）。结果：恶性肿瘤Cho、Cr及Cho/Cr平均值分别为20.52±8.42、6.33±3.26、3.25±1.45,良性肿瘤Cho、Cr及Cho/Cr平均值分别为9.36±4.63、6.25±3.03、1.50±0.31,恶性肿瘤较良性肿瘤Cho、Cho/Cr明显增高,具有统计学差异（P<0.05）,两者的Cr值无明显统计学差异（P>0.05）。结论：1H-MRS分析Cho及Cho/Cr对四肢软组织肿瘤良恶性的定性具有重要价值。     

颅内疾病诊断中质子MRI波谱脂质峰升高的意义

目的探讨颅内疾病诊断中质子MRI波谱脂质(Lip)峰升高的意义。方法统计分析2012年1月至2014年1月收治的100例颅内肿瘤及非肿瘤性病变患者的临床资料。结果各种不同疾病类型Lip峰阳性率之间的差异均有统计学意义(均P<0.05)。高度恶性脑肿瘤组患者的胆碱/肌酸(Cho/Cr)、胆碱/N-乙酰天门冬氨酸(Cho/NAA)比值均明显良性病变组和低度恶性脑肿瘤组,差异有统计学意义(P<0.05),但良性病变组和低度恶性脑肿瘤组患者的Cho/Cr、Cho/NAA值差异无统计学意义(P>0.05)。结论质子MRI波谱Lip峰升高能够将不同病理变化有效反映出来,Lip峰联合Cho峰及常规MRI在颅内疾病诊断中发挥重要作用。     

1HMRS在鉴别脑内单发环形强化病变中的应用

目的：分析3.0T氢质子磁共振波谱成像（1HMRS）在鉴别脑内单发环形强化病变中的应用。方法应用PHILIPS 3.0T磁共振扫描仪对65例在MRI增强扫描时表现为脑内单发环形强化病变的患者治疗前行1HMRS扫描,经病理证实或临床确诊为30例高级别胶质瘤、23例单发脑转移瘤和12例脑脓肿。分别测量病灶中心及周围水肿区的NAA、Cho及Cr峰的峰下面积,计算NAA/Cr、Cho/Cr、NAA/Cho比值,并记录病灶中心Lac和Lip峰是否出现。对各参数值进行统计学分析,明确其对鉴别三种疾病的诊断价值。结果病灶中心的Cho值胶质瘤﹥转移瘤﹥脑脓肿;Cho/Cr值胶质瘤﹥脑脓肿（P﹤0.05）;NAA/Cho值脑脓肿﹥转移瘤﹥高级别胶质瘤;NAA及NAA/Cr在三组之间差异均无统计学意义。周围水肿区的NAA/Cr转移瘤组﹥脑脓肿组;Cho/Cr比值差异有显著统计学意义（P﹤0.001）,胶质瘤组﹥脑脓肿组﹥转移瘤组,高级别胶质瘤组明显高于单发脑转移瘤组（P=0.000）且Cho/Cr临界值为1.5650时诊断为高级别胶质瘤的敏感度为73.3%,特异度为94.4%,ROC曲线下面积为0.921。周围水肿区NAA/Cho差异有显著统计学意义（P﹤0.001）,转移瘤组高于胶质瘤组和脑脓肿组。高级别胶质瘤Lip峰出现率低于转移瘤和脑脓肿,转移瘤和脑脓肿组间比较差异无统计学意义。结论1HMRS可用于鉴别脑内单发环形强化病变,病灶中心的NAA/Cho和周围水肿区的Cho/Cr比值对高级别胶质瘤、单发脑转移瘤和脑脓肿的鉴别诊断具有重要意义。     

多体素1H磁共振波谱在脑胶质瘤诊断及分级中的应用研究

 目的　探讨多体素1H磁共振波谱在脑胶质瘤诊断及分级中的价值。方法　选取经手术病理或临床确诊的36例脑胶质瘤患者。采用美国GE公司Signa EXCITE HD 3.0T 超导型磁共振（MR）扫描仪对所有患者行颅脑常规核磁共振（MRI）扫描和二维多体素144 ms序列扫描。采用Functool软件包后处理,分别测定病变实质、病变周围及健侧相应区域的胆碱（Cho）／肌酸（Cr）、Cho／N-乙酰天门冬氨酸（NAA）、NAA／Cr比值及肌醇（MI）值的变化,并对结果进行统计学分析。结果　全组数据采用SAS8.2软件处理,结果显示：低级别胶质瘤和高级别胶质瘤瘤体区Cho／Cr、Cho／NAA、NAA／Cr比值及MI值分别比较差异有统计学意义（P＜0.05）;瘤周水肿区Cho／Cr、NAA／Cr比值分别比较差异有统计学意义（P＜0.05）,MI值比较差异无统计学意义（P＞0.05）。结论　1H-MRS在鉴别诊断脑胶质瘤中有重要价值,结合MR其他成像方法可对其做出较为准确的分级。     

常规MRI与1H-MRS结合鉴别高级别脑胶质瘤与单发性脑转移瘤

目的 探讨常规磁共振成像（MRI）与氢质子磁共振波谱（1H-MRS）相结合在高级别脑胶质瘤与单发性脑转移瘤中诊断及鉴别诊断的价值。方法 选取我院收治经手术病理组织学证实的高级别脑胶质瘤患者27例与单发性脑转移瘤患者21例,进行常规MRI及1H-MRS检查。分析比较常规MRI的影像表现特征及1H-MRS代谢产物［N-乙酰天门冬氨酸（NAA）、胆碱（Cho）和肌酸（Cr）］变化情况。结果 常规MRI显示仅病变部位和水肿程度在两者间存在差异（P＜0.05）。1H-MRS高级别脑胶质瘤与单发性脑转移瘤瘤体区Cho／NAA值比较差异有统计学意义（P＜0.05）,而NAA／Cr、Cho／Cr值比较差异无统计学意义（P＞0.05）;两者瘤周区Cho／Cr、Cho／NAA值比较差异均有统计学意义（P＜0.05）,而NAA／Cr值比较差异无统计学意义（P＞0.05）。结论 常规MRI与1H-MRS相结合使高级别脑胶质瘤与单发性脑转移瘤诊断及鉴别诊断的准确性得到进一步提高,具有较高的临床应用价值。     

诱导小鼠肝硬化对结肠癌肝转移的抵抗作用

目的:研究诱导小鼠肝硬化对结肠癌肝转移的抵抗作用及其可能的机制。方法:诱导小鼠肝硬化及结肠癌肝转移模型,比较正常肝与肝硬化小鼠肝转移率;免疫组化法测定层粘连蛋白(laminin,LN)、纤维连接蛋白(fibronectin,FN)及E-选择素(E-selectin)在小鼠肝脏的表达。结果:①肝硬化小鼠肝转移率(4/16,25%)低于正常肝小鼠(14/16,87.5%)(P=0.001);②肝硬化后移植瘤小鼠LN、FN表达高于正常肝移植瘤小鼠,E-selectin表达低于正常肝移植瘤小鼠。结论:动物实验证实肝硬化对结肠癌肝转移有抵抗作用;LN、FN及E-selectin在此过程中可能起一定作用。     

肝细胞癌乙型肝炎病毒感染与人胎盘型谷胱甘肽S-转移酶的表达

背景与目的：许多肿瘤癌变过程中人胎盘型谷胱甘肽S－转移酶（glutathione S-transferases,GST-π）的表达会异常升高,其变化早于细胞的形态改变。探讨肝细胞癌乙型肝炎病毒（hepatitis B virus,HBV)感染与GST－π表达的关系。方法：对肝细胞癌和相关慢性肝病及正常肝组织共86例用免疫组化染色方法检测乙型肝炎表面抗原（hepatitis B surface antigen,HBsAg）、乙型肝炎核心抗原（hepatitis B core antigen,HBcAg）和GST－π,用原位分子杂交方法检测乙型肝炎病毒DNA（hepatitis B virus DNA,HBVDNA)。结果：HBsAg,HBcAg和HBVDNA的阳性率在慢性肝炎分别为61．9％（13／21）;42．9％（9／21）和75．0％（12／16）;在肝硬化分别为64．0％（16／25）,36．0％（9／25）和83．3％（15／18）;在癌旁肝硬化分别为72．7％（16／22）,61．1％（11／18）和85．7％（12／14）;在肝细胞癌分别为45．2％（14／31）,50．0％（14／28)和64．3％（9／14）。其中以癌旁肝硬化组阳性率最高。慢性肝炎、肝硬化和癌旁肝硬化HBVDNA阳性信号较肝细胞癌多而强。GST－π在慢性肝炎（25．0％,4／16）、肝硬化（17．6％,3／17）、癌旁肝硬化（53．3％,8／15）和肝细胞癌（60．0％,9／15）均有表达,但癌旁肝硬化组和肝细胞癌组阳性率明显增高,癌旁肝硬化（53．3％,8／15）和肝细胞癌（60．0％,9／15）均有表达,但癌旁肝硬化组和肝细胞癌组阳性率明显增高,癌旁肝硬化组与不伴肝癌的肝硬化组差异有显著性（P＜0．05）,与肝细胞癌组差异无显著性（P＞0．05）。结论：大多数肝细胞癌与HBV感染所致的慢性肝炎和肝硬化密切相关,HBV感染可能导致GST－π的表达升高。癌旁的肝硬化比不伴癌的肝硬化更具癌前病变的特点。     

Risk of liver cancer among US male veterans with cirrhosis, 1969-1996

Background:

Liver cancer incidence rates in the United States have increased for several decades for reasons that are not entirely clear. Regardless of aetiology, cirrhosis is a strong risk factor for liver cancer. As mortality from cirrhosis has been declining in recent decades, it is possible that the risk of liver cancer among persons with cirrhosis has been affected.

Methods:

Data from the US Veterans Affairs medical records database were analysed after adjustment for attained age, race, number of hospital visits, obesity, diabetes, and chronic obstructive pulmonary disease. Hazard ratio (HR) and 95% confidence interval (95% CI) were calculated using Cox proportional hazards modelling. Survival analyses were conducted using age as the time metric and incidence of cirrhosis as a time-dependent covariate.

Results:

Among 103 257 men with incident cirrhosis, 788 liver cancers developed. The HR of liver cancer was highest among men with viral-related cirrhosis (HR=37.59, 95% CI: 22.57–62.61), lowest among men with alcohol-related cirrhosis (HR=8.20, 95% CI: 7.55–8.91) and intermediate among men with idiopathic cirrhosis (HR=10.45, 95% CI: 8.52–12.81), when compared with those without cirrhosis. Regardless of cirrhosis type, white men had higher HRs than black men. The HR of developing liver cancer increased from 6.40 (95% CI: 4.40–9.33) in 1969–1973 to 34.71 (95% CI: 23.10–52.16) in 1992–1996 for those with cirrhosis compared with those without.

Conclusion:

In conclusion, the significantly increased HR of developing liver cancer among men with cirrhosis compared with men without cirrhosis in the United States may be contributing to the increasing incidence of liver cancer.     

乙肝肝硬化患者抗病毒治疗后肝癌发生的危险因素分析

目的:探讨乙肝肝硬化患者抗病毒治疗后仍然进展为肝细胞肝癌的危险因素。方法:纳入2014年7月至2017年7月我院收治的72例乙肝肝硬化患者的临床资料。根据乙肝肝硬化患者抗病毒治疗满1年后是否进展为肝细胞肝癌分为肝癌组(21例)和肝硬化组(51例)。收集两组患者临床资料，采用统计软件SPSS 21.0进行数据分析，将两组间差异有统计学意义的指标作为自变量，对自变量行Logistic单因素和多因素回归分析，探究乙肝肝硬化患者进展为肝细胞肝癌的独立危险因素。结果:对比两组患者的临床资料，发现性别、年龄、家族史、糖尿病史、谷草转氨酶(AST)及抗病毒治疗12周病毒学应答指标有差异，且差异具有统计学意义(P＜0.05)；对自变量行Logistic单因素和多因素回归分析，结果发现男性、年龄≥48岁和抗病毒治疗前AST≥40 U/L是乙肝肝硬化患者经抗病毒治疗后进展为肝细胞肝癌的独立危险因素(P＜0.05)。结论:男性、年龄大(≥48岁)和抗病毒治疗前AST≥40 U/L是乙肝肝硬化患者经抗病毒治疗后进展为肝细胞肝癌的独立危险因素。     

TGF-Β1 & PNPLA3 Genetic Variants and the Risk of Hepatic Fibrosis and HCC in Egyptian Patients with HCV-Related Liver Cirrhosis

Objective: The clinical outcomes of hepatitis C virus (HCV) infection and its sequelae including liver cirrhosis and hepatocellular carcinoma (HCC) are greatly affected by host genetic factors; however, the possible mechanisms are still largely unclear. This work aimed to assess transforming growth factor-β1 (TGF-β1), and patatin-like phospholipase domain containing-protein 3 (PNPLA3) genetic variants as risk factors for hepatic fibrosis and hepatocellular carcinoma (HCC) in Egyptian patients with HCV-related liver cirrhosis. Methods: Seventy HCV-related liver cirrhosis patients (Total cirrhosis) who were divided into two groups; 34 patients with HCC (HCC group), and 36 patients without HCC (LC group) and 20 healthy volunteers (control group) were included. Routine laboratory investigations and imaging studies were determined. TGF-β1 (Arg25Pro; 915G>C) and PNPLA3 (I148M; C>G) variants were evaluated using real-time polymerase chain reaction (real-time PCR). Results: HCC group showed a significantly higher GG genotype distribution of TGF-β1 (Arg25Pro) than the LC group (P= 0.008, OR: 7.083, CI 95%: 1.422 – 35.282). The distributions of GG genotype (P= 0.047) and G allele (P= 0.002, OR: 4.395, CI 95%: 1.622 – 11.911) of PNPLA3 (I148M) were significantly higher in total cirrhosis patients than controls. Conclusion: TGF-β1 (Arg25Pro) GG variant may be associated with HCC risk in HCV-related liver cirrhosis patients, while PNPLA3 (I148M) GG variant may be associated with cirrhosis development but not HCC risk in HCV-related liver cirrhosis patients.     

Clinicomorphological manifestations of primary liver carcinoma (PLC) in liver cirrhosis

Among 200 deaths from liver cirrhosis the clinical and autopsy records of 30 histologically confirmed cases of primary liver carcinoma (PLC) were reviewed. Male to female ratio was 5:1. Biopsy-proven liver lesions reflected chronic liver disease, mainly cirrhosis. Autopsy-PLC detected was classified as hepatocellular carcinoma (21 cases) with trabecular and pseudoglandular histological pattern, cholangiocarcinoma (two cases), and hemangiosarcoma. This retrospective analysis pointed to the relationship between PLC and liver cirrhosis, the latter being the primary risk factor for the incidence of PLC in Slovenia (Yugoslavia).     

Potential of Apolipoprotein A1 (ApoA1) for Detecting Liver Cirrhosis and Hepatocellular Carcinoma

Objective: Liver cirrhosis and hepatocellular carcinoma (HCC) are chronic liver diseases that can cause serious health problems. Meanwhile, the methods used to detect liver cirrhosis and HCC are limited. Apolipoprotein A1 (ApoA1) is a protein that makes up high-density lipoprotein (HDL), which plays a role in liver cirrhosis and HCC, and can be used as a biomarker. This study aims to determine the ability of ApoA1 to detect and differentiate liver cirrhosis and hepatocellular carcinoma. Methods: This cross-sectional study was conducted on 47 patients with liver cirrhosis and HCC at Margono Soekarjo Regional General Hospital, Purwokerto, Indonesia. This study also involved 33 healthy participants from blood donors at the Blood Transfusion Unit, Indonesian Red Cross, Banyumas. Serum ApoA1 levels were analyzed by ELISA method. Receiver Operating Characteristics (ROC) were used to evaluate the diagnostic power of ApoA1 and differentiate between cirrhotic, HCC, and healthy patients. Multivariate binary logistic regression test to determine the most influential variables on the incidence of cirrhosis, HCC, and health. Results: ApoA1 was able to differentiate cirrhosis from HCC, cirrhosis from healthy and HCC from healthy, with sensitivity 56.7%, 86.7%, 70.6%, specificity 70.6%, 93.9%, 84.9%, respectively, and AUC 68.5%, 92.6%, 75.0%. AFP (p = 0.002, OR 1.004) and bilirubin (p = 0.021, OR 1.259) were variables that contributed to cirrhosis - HCC. Age (p = 0.011, OR 0.766) and AST (p = 0.003, OR 0.834) are variables that play a role in health - cirrhosis. ALT (p = 0.024, OR 0.965) and PT (p = 0.004, OR 0.253) are variables that play a role in healthy - HCC. Conclusion: ApoA1 was best for detecting healthy from cirrhosis, followed by healthy from HCC and cirrhosis from HCC. ApoA1 is not the primary variable determining the incidence of cirrhosis - HCC, healthy - HCC, and healthy – HCC.     

大肠癌并肝硬化与大肠癌不并肝硬化发生肝转移癌对照研究

目的 探讨大肠癌并肝硬化患者发生肝转移癌的规律。方法 回顾性分析我院1990年1月～2001年1月10年间诊治的大肠癌856例,均有病理组织学检查确诊。其中大肠癌并肝硬化患者(肝硬化组)74例,伴肝转移癌者2例;其余为不并肝硬化患者(非肝硬化组)782例,伴肝转移癌者168例。结果 肝硬化组肝转移癌发生率为2.7％(2/74);非肝硬化组肝转移癌发生率为21.5％(168/782,P<0.001)。结论 大肠癌不并肝硬化患者的肝转移癌发生率同大肠癌并肝硬化患者的肝转移癌发生率比较,前者肝转移癌发生率明显地高,后者很少发生肝转移癌。     

人类肝癌发生过程中cyclinD1和CDK4及p16蛋白的表达

目的研究肝细胞癌(HCC)发生过程中细胞周期调控因子cyclinD1、CDK4和p16蛋白表达及其意义。方法应用免疫组织化学SP染色法检测正常肝组织、慢性肝炎、肝硬化、癌周肝硬化和肝癌组织中cyclinD1、CDK4和p16蛋白表达。对免疫组化结果进行计算机图象定量分析。结果cyclinD1、CDK4和p16蛋白的阳性单位(positive unit,PU)和面数密度(area number density,NA)从慢性肝炎(PU分别为39.4、41.0和33.3;NA分别为236.7、272.7和237.4)、肝硬化(PU分别为40.8、45.2和43.6;NA分别为313.8、354.6和322.9)、癌周肝硬化(PU分别为55.5、59.4和54.4;NA分别为481.9、488.9和432.6)到肝癌(PU分别为59.6、63.7和58.1;NA分别为549.2、587.7和451.3)表达逐渐增强。癌周肝硬化和肝癌组织中cyclinD1、CDK4、p16的表达明显高于慢性肝炎和肝硬化(P值分别为0.034、0.020、0.030、0.007、0.003和0.005),但癌周肝硬化和肝癌组织之间差异无统计学意义,P值分别为0.433、0.535和0.447。慢性肝炎和肝硬化中cy-clinD1、CDK4、p16阳性信号主要定位于胞核,而癌周肝硬化和HCC中主要定位于胞质。p16与HCC的分化程度有关,但未发现cyclinD1、CDK4与肿瘤分化程度之间有相关性。结论cyclin-细胞周期蛋白依赖性激酶(CDKs)-细胞周期蛋白依赖性激酶抑制因子(CKIs)调控网络中,相关调控因子的异常可能参与了HCC的发生、发展。cyclinD1、CDK4的过度表达可能是肝癌发生过程中的早期事件。在HCC的发生过程中p16高表达可能是细胞周期正反馈调控的结果,在HCC的发生中可能属于早期事件,而p16表达下降或缺失可能是肝癌发生过程中的晚期事件。