软肝方与介入疗法治疗根治术后小肝癌的长期疗效比较及影响因素分析
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摘要
目的：比较软肝方(原名软坚护肝片)与介入疗法治疗根治术后小肝癌的长期疗效差异,验证“根治术后小肝癌患者使用中医药预防其复发的效果会比介入疗法更好”的假说。
方法：在导师治疗肝癌遣方用药经验总结和我研究中心前期临床研究的基础上建立“根治术后小肝癌患者使用中医药预防其复发的效果会比介入疗法更好”的假说。通过病案信息科计算机数据库,使用国际疾病分类(ICD)编码查询1987.1-2008.12期间在广西医科大学第一附属医院肝胆外科和微创肿瘤外科病房行手术切除的所有原发性肝癌患者,手术标本均经病理检查证实为肝细胞癌,最终将399例根治术后小肝癌患者纳入验证假说的队列,其中346例为男性患者,53例为女性患者。按照根治术后小肝癌患者接受TCM治疗的暴露程度不同分为四组：(1)TCMO组(2)TCM与介入治疗术联合组(TCM-IT)(3)介入治疗组(ITO)(4)单纯手术组(SO)。生存率评估采用Kaplan-Meier生存分析法,组间生存率的差异比较采用Log-rank检验,寿命表法估算逐年复发率。预后多因素分析采用Cox比例风险模型回归分析,通过最终长期生存率结果比较,验证假说的成立。
结果：对住院行根治术的399例小肝癌患者进行回顾性队列研究,随访至2009-02-28。对所有患者的基线资料进行分析,仅在肿瘤位置上四组差异有统计学意义(P=0.036)。
TCMO组与ITO组1,2,3,5、10、15年总生存率(OS)分别为94.76%vs91.85%、91.69% vs74.42%、89.27% vs55.74%、83.94% vs45.50%、71.22%vs33.34%、55.58% vs9.26%(p=0.000,HR=0.210,95%CI:0.126-0.348),两组1,2,3,5、10、15的无病生存率分别(DFS)为85.30% vs81.60%、81.40% vs73.10%、76.10% vs57.10%. 69.80% vs45.00%、54.00% vs30.80%、44.50% vs0%(p=0.001,HR=0.518,95%CI: 0.341-0.788);
TCMOvsTCM-IT组1,2,3,5、10、15年总生存(OS)率分别为94.76%vs98.53%,91.69% vs93.38%,89.27% vs87.54%,83.94% vs74.16%,71.22% vs57.10%,55.58% vs0%(Log Rank检验x2=2.365,p=0.124)；两组1,2,3,5、10、15年无病生存(DFS)率85.30% vs92.50%,81.40% vs83.30%,76.10% vs83.30%,69.80% vs76.20%, 54.00% vs62.20%,44.50% vs0%, (Log Rank检验x2=0.710,p=0.399)。两组(OS)率和(DFS)率比较差异无统计学意义；
TCM-IT组总生存率和无病生存期率均高于ITO组,差异有统计学意义(P<0.05);
TCMO组总生存率、无病生存率均高于SO组,差异有统计学意义(P<0.05)；
ITO组总生存率高于SO组,差异有统计学意义(P<0.05)；ITO组vs SO组生存率无病生存率统计数据显示无明显差异(P>0.05)。
总的中位生存时间分别是151.20月(TCM-IT组)、43.87月(ITO组)、20.77月(SO),而TCMO组由于各时间段对应的生存率均大于50%。
中位无病生存时间分别是152.900月(TCMO组),51.733月(ITO组),76.667月(SO组)(P<0.0001),而TCM-IT组由于各时间段对应的无病生存率均大于50%; TCMO组vs ITO组1,2,3,5年逐年复发率为15% vs19%、5% vs100%、4% vs12%、5%vs4%(P=0.002),两组差异有统计学意义。
单因素分析显示与总生存期(OS)相关的预后因素分析是：家族史、球蛋白、肿瘤个数、血管侵犯、肿瘤位置、child分级、TNM分期、治疗方式(P<0.05)。Cox多因素分析结果显示治疗方式、肿瘤大小、就医方式、TNM分期、家族史、性别6个变量为影响根治术后小肝癌患者生存期(OS)的独立风险因素；Cox多因素分析显示就医方式、性别、以及group 1 (TCMO group versus ITO group) (HR=0.210,95%CL 0.126-0.348)、group3 (TCM-IT group vs ITO group) (HR=0.294,95%CL 0.174-0.496)的回归系数均<0是保护因素,其中ITO组的死亡风险均高于TCMO组、TCM-IT组,分别是TCMO组,TCM-IT组的4.76倍、3.40倍。而group2 (SO group versus ITO group) (HR=2.613,95%CL 1.663-4.106)、肿瘤大小、TNM分期、家族史的回归系数>0是危险因素,其中SO组死亡风险是ITO组的2.613倍。
单因素显示与无病生存期(DFS)相关的预后因素具体为：年龄、AFP、肿瘤包膜、TNM分期、治疗方式(P＜0.05); Cox多因素分析结果显示治疗方式和TNM分期2个变量为影响肝癌无病生存期的独立风险因素,其中group1 (TCMO versus ITO group)属保护性因素(P=0.002,HR=0.518,95%CL0.341-0.788),显示介入治疗组复发风险是TCMO组1.93倍；group2(SO group versus ITO group) (HR=1.107,95%CL0.609-2.011)是危险因素,显示单纯手术组复发风险是介入治疗组的1.107倍；：group3 (TCM-IT group vs ITO group)属保护性因素(P=0.001,HR=0.401,95%CL0.233-0.690),介入治疗组复发风险是联合治疗组的2.49倍。
结论：长期口服软肝方能够明显延长根治术后小肝癌患者的无病生存时间和总生存时间、降低复发率,其结果有待于进一步前瞻性随机对照研究验证。
Objectives:
To compare long-term effectiveness of ruanganfang (RGF), originally named ruanjianhugan (RJH) tablets,a form of traditional Chinese medicine (TCM), with interventional therapy (IT) after resection of small hepatocellular carcinoma (HCC), and provid a reliable proof for the hypothesis that TCM would be more effective than interventional therapy in preventing HCC recurrence and prolonging survival after curative resections for small HCC.
Methods:
On the basis of Professor Ling Changquan's experience in treating primary liver cancer and previous research in Department of Traditional Chinese Medicine, Changhai Hospital,a hypothesis that TCM would be more effective than intervcntional therapy in prolonging survival after curative resections for small HCC was built up.
From January 1987 to December 2008, all the consecutive patients with HCC underwent curative resection from the Department of Medical Records according to the International Classification of Diseases, tenth Revision, Clinical Modification (ICD-10) diagnosis Codes for HCC were included, the patients came from the Department of Hepatobiliary Surgery and Center of Minimally Invasive Surgery of the First Affiliated Hospital of Guangxi Medical University, Nanning,399 patients with small HCC were analyzed by a retrospective cohort study (346 men and 53 women). Subjects were separated into four groups based on different therapy modes:a TCM-only (TCMO) group, a TCM combined with interventional therapy (TCM-IT) group, an interventional therapy-only(ITO)group, and a simple operation (SO) group. Prognostic factors were correlated with disease-free survival (DFS) and overall survival (OS); DFS and OS rates were calculated with the Kaplan-Meier method, and multivariate analyses for factors affecting survival were evaluated by the Cox proportional hazard model. The accuracy of the former theories hypothesis was verified.
Results:The retrospective cohort study of 399 patients with small HCC was stopped on February 28,2009. about the base-line information of the patients, Only tumor location was considered significant (P=0.036).
Overall survival rates at1,2,3,5,10,and15 years of the TCMO patients and the ITO patients were 94.76% and 91.85%,91.69% and 74.42%,89.27% and 55.74%,83.94% and 45.50%,71.22% and 33.34%,55.58% and 9.26% respectively (risk ratio 0.210,95% confidence interval 0.126-0.348, P=0.000). There was a significant difference in DFS rates between the TCMO and ITO groups at 1,2,3,5,10, and 15 years (85.30% vs 81.60%,81.40%vs73.10%,76.10%vs57.10%,69.80%vs45.00%,54.00%vs30.80%, 44.50%vs0%, respectively; risk ratio 0.518,95% confidence interval 0.341-0.788, P= 0.001);
1,2,3,5,10,15-year OS rates in patients with TCMO group and in TCM-IT group were 94.76% vs98.53%,91.69% vs93.38%,89.27% vs87.54%,83.94% vs74.16%, 71.22% vs57.10%,55.58% vs 0%, respectively (log-rank test,χ2=2.365; P=0.124), while 1,2,3,5,10,15-year DFS rates in patients with TCMO group and TCM-IT group were 85.30% vs92.50%,81.40% vs83.30%,76.10% vs83.30%,69.80% vs76.20%, 54.00% vs62.20%,44.50% vs0%, respectively (log-rank test,χ2=0.710, P=0.399), there was no significant difference between the two groups;
The OS and DFS rates in TCM-IT patients were higher compared with ITO patients, and the difference was significant (P＜0.05)
The OS rates in TCMO patients were higher compared with SO patients, and the difference was significant (P＜0.05),While the difference between the TCMO and SO patients was not significant (P>0.05)
The overall median survival time was 151.20 months (TCM-IT),43.87 months (ITO), and 20.77 months (SO). While the survival rates of TCMO group were higher than 50%, the median survival time of the TCMO group can not be calculated.
The median DFS times were 152.900 months (TCMO),51.733 months (ITO), and 76.667 months (SO), respectively.The median DFS times of the SO and TCMO groups were both longer than the median DFS times of the ITO, the median survival time of the TCM-IT group can not be calculated.
The 1-,2-,3-, and 5-year recurrence rates in patients with TCMO group and the ITO groupwere 15% and 19%,5% and 10%,4% and 12%, and 5% and 4%, respectively; the difference was significant (P=0.002).
Univariate analysis for OS were calculated for patient showed the significant prognostic factors were family history, globulin, tumor number, vascular invasion, tumor location, Child-Pugh classification, TNM staging, and therapy mode (P< 0.05).Multivariate survival analysis by Cox proportional hazard model, the six independent factors were as follows:therapy mode, tumor size, seeking behavior, TNM staging, family history, sex. Results of the multivariate survival analysis also showed group 2 (so group versus ITO group), tumor size, TNM staging, and family history were major risk factors of recurrence for small HCC tumors (P< 0.05, regression coefficient>0, relative risk 2.613,1.210,1.365,2.104), while seeking behavior, sex, the group 1(TCMO group versus ITO group) and group 3 (TCM-IT group vs ITO group) using different therapy mode were protective factors (P<0.05, regression coefficient<0, relative risk 0.659,0.431, 0.210,0.294).The results showed that the risk of death from HCC in ITO was 4.76 times and 3.40 times higer than the TCMO and TCMO-ITgroup.
Univariate analysis for DFS were performed on the patients with different group,and results showed the significant prognostic factors (P<0.05)including age, AFP,Tumor capsule,TNM staging, therapy mode.Multivariate survival analysis showed the two independent factors were therapy mode and TNM staging. Results of the multivariate survival analysis also showed group 1(TCMO versus ITO group) was major protective factor of recurrence for small HCC tumors (P=0.002,HR=0.518,95%CL0.341-0.788), The results of the multivariate survival analysis showed that the risk of recurrence in ITO patients was 1.93 times than in TCMO patients. While group 2 (SO group versus ITO group)was major risk factor, the risk of recurrence in SO patients was 1.107 times than in ITO. While Group3 (TCM-IT group vs ITO group) was the protective factor (P=0.001,HR= 0.401,95%CL0.233-0.690), showed that the risk of recurrence of IT group was 2.49 than TCM-IT group.
Conclusions:
Long-term oral use of ruanganfang (RGF) (originally named ruanjianhugan tablets) can improve significantly DFS and OS for small-HCC after resection compared with interventional therapy. Randomized, controlled trials are needed to confirm the findings of this study.
方法：在导师治疗肝癌遣方用药经验总结和我研究中心前期临床研究的基础上建立“根治术后小肝癌患者使用中医药预防其复发的效果会比介入疗法更好”的假说。通过病案信息科计算机数据库,使用国际疾病分类(ICD)编码查询1987.1-2008.12期间在广西医科大学第一附属医院肝胆外科和微创肿瘤外科病房行手术切除的所有原发性肝癌患者,手术标本均经病理检查证实为肝细胞癌,最终将399例根治术后小肝癌患者纳入验证假说的队列,其中346例为男性患者,53例为女性患者。按照根治术后小肝癌患者接受TCM治疗的暴露程度不同分为四组：(1)TCMO组(2)TCM与介入治疗术联合组(TCM-IT)(3)介入治疗组(ITO)(4)单纯手术组(SO)。生存率评估采用Kaplan-Meier生存分析法,组间生存率的差异比较采用Log-rank检验,寿命表法估算逐年复发率。预后多因素分析采用Cox比例风险模型回归分析,通过最终长期生存率结果比较,验证假说的成立。
结果：对住院行根治术的399例小肝癌患者进行回顾性队列研究,随访至2009-02-28。对所有患者的基线资料进行分析,仅在肿瘤位置上四组差异有统计学意义(P=0.036)。
TCMO组与ITO组1,2,3,5、10、15年总生存率(OS)分别为94.76%vs91.85%、91.69% vs74.42%、89.27% vs55.74%、83.94% vs45.50%、71.22%vs33.34%、55.58% vs9.26%(p=0.000,HR=0.210,95%CI:0.126-0.348),两组1,2,3,5、10、15的无病生存率分别(DFS)为85.30% vs81.60%、81.40% vs73.10%、76.10% vs57.10%. 69.80% vs45.00%、54.00% vs30.80%、44.50% vs0%(p=0.001,HR=0.518,95%CI: 0.341-0.788);
TCMOvsTCM-IT组1,2,3,5、10、15年总生存(OS)率分别为94.76%vs98.53%,91.69% vs93.38%,89.27% vs87.54%,83.94% vs74.16%,71.22% vs57.10%,55.58% vs0%(Log Rank检验x2=2.365,p=0.124)；两组1,2,3,5、10、15年无病生存(DFS)率85.30% vs92.50%,81.40% vs83.30%,76.10% vs83.30%,69.80% vs76.20%, 54.00% vs62.20%,44.50% vs0%, (Log Rank检验x2=0.710,p=0.399)。两组(OS)率和(DFS)率比较差异无统计学意义；
TCM-IT组总生存率和无病生存期率均高于ITO组,差异有统计学意义(P<0.05);
TCMO组总生存率、无病生存率均高于SO组,差异有统计学意义(P<0.05)；
ITO组总生存率高于SO组,差异有统计学意义(P<0.05)；ITO组vs SO组生存率无病生存率统计数据显示无明显差异(P>0.05)。
总的中位生存时间分别是151.20月(TCM-IT组)、43.87月(ITO组)、20.77月(SO),而TCMO组由于各时间段对应的生存率均大于50%。
中位无病生存时间分别是152.900月(TCMO组),51.733月(ITO组),76.667月(SO组)(P<0.0001),而TCM-IT组由于各时间段对应的无病生存率均大于50%; TCMO组vs ITO组1,2,3,5年逐年复发率为15% vs19%、5% vs100%、4% vs12%、5%vs4%(P=0.002),两组差异有统计学意义。
单因素分析显示与总生存期(OS)相关的预后因素分析是：家族史、球蛋白、肿瘤个数、血管侵犯、肿瘤位置、child分级、TNM分期、治疗方式(P<0.05)。Cox多因素分析结果显示治疗方式、肿瘤大小、就医方式、TNM分期、家族史、性别6个变量为影响根治术后小肝癌患者生存期(OS)的独立风险因素；Cox多因素分析显示就医方式、性别、以及group 1 (TCMO group versus ITO group) (HR=0.210,95%CL 0.126-0.348)、group3 (TCM-IT group vs ITO group) (HR=0.294,95%CL 0.174-0.496)的回归系数均<0是保护因素,其中ITO组的死亡风险均高于TCMO组、TCM-IT组,分别是TCMO组,TCM-IT组的4.76倍、3.40倍。而group2 (SO group versus ITO group) (HR=2.613,95%CL 1.663-4.106)、肿瘤大小、TNM分期、家族史的回归系数>0是危险因素,其中SO组死亡风险是ITO组的2.613倍。
单因素显示与无病生存期(DFS)相关的预后因素具体为：年龄、AFP、肿瘤包膜、TNM分期、治疗方式(P＜0.05); Cox多因素分析结果显示治疗方式和TNM分期2个变量为影响肝癌无病生存期的独立风险因素,其中group1 (TCMO versus ITO group)属保护性因素(P=0.002,HR=0.518,95%CL0.341-0.788),显示介入治疗组复发风险是TCMO组1.93倍；group2(SO group versus ITO group) (HR=1.107,95%CL0.609-2.011)是危险因素,显示单纯手术组复发风险是介入治疗组的1.107倍；：group3 (TCM-IT group vs ITO group)属保护性因素(P=0.001,HR=0.401,95%CL0.233-0.690),介入治疗组复发风险是联合治疗组的2.49倍。
结论：长期口服软肝方能够明显延长根治术后小肝癌患者的无病生存时间和总生存时间、降低复发率,其结果有待于进一步前瞻性随机对照研究验证。
Objectives:
To compare long-term effectiveness of ruanganfang (RGF), originally named ruanjianhugan (RJH) tablets,a form of traditional Chinese medicine (TCM), with interventional therapy (IT) after resection of small hepatocellular carcinoma (HCC), and provid a reliable proof for the hypothesis that TCM would be more effective than interventional therapy in preventing HCC recurrence and prolonging survival after curative resections for small HCC.
Methods:
On the basis of Professor Ling Changquan's experience in treating primary liver cancer and previous research in Department of Traditional Chinese Medicine, Changhai Hospital,a hypothesis that TCM would be more effective than intervcntional therapy in prolonging survival after curative resections for small HCC was built up.
From January 1987 to December 2008, all the consecutive patients with HCC underwent curative resection from the Department of Medical Records according to the International Classification of Diseases, tenth Revision, Clinical Modification (ICD-10) diagnosis Codes for HCC were included, the patients came from the Department of Hepatobiliary Surgery and Center of Minimally Invasive Surgery of the First Affiliated Hospital of Guangxi Medical University, Nanning,399 patients with small HCC were analyzed by a retrospective cohort study (346 men and 53 women). Subjects were separated into four groups based on different therapy modes:a TCM-only (TCMO) group, a TCM combined with interventional therapy (TCM-IT) group, an interventional therapy-only(ITO)group, and a simple operation (SO) group. Prognostic factors were correlated with disease-free survival (DFS) and overall survival (OS); DFS and OS rates were calculated with the Kaplan-Meier method, and multivariate analyses for factors affecting survival were evaluated by the Cox proportional hazard model. The accuracy of the former theories hypothesis was verified.
Results:The retrospective cohort study of 399 patients with small HCC was stopped on February 28,2009. about the base-line information of the patients, Only tumor location was considered significant (P=0.036).
Overall survival rates at1,2,3,5,10,and15 years of the TCMO patients and the ITO patients were 94.76% and 91.85%,91.69% and 74.42%,89.27% and 55.74%,83.94% and 45.50%,71.22% and 33.34%,55.58% and 9.26% respectively (risk ratio 0.210,95% confidence interval 0.126-0.348, P=0.000). There was a significant difference in DFS rates between the TCMO and ITO groups at 1,2,3,5,10, and 15 years (85.30% vs 81.60%,81.40%vs73.10%,76.10%vs57.10%,69.80%vs45.00%,54.00%vs30.80%, 44.50%vs0%, respectively; risk ratio 0.518,95% confidence interval 0.341-0.788, P= 0.001);
1,2,3,5,10,15-year OS rates in patients with TCMO group and in TCM-IT group were 94.76% vs98.53%,91.69% vs93.38%,89.27% vs87.54%,83.94% vs74.16%, 71.22% vs57.10%,55.58% vs 0%, respectively (log-rank test,χ2=2.365; P=0.124), while 1,2,3,5,10,15-year DFS rates in patients with TCMO group and TCM-IT group were 85.30% vs92.50%,81.40% vs83.30%,76.10% vs83.30%,69.80% vs76.20%, 54.00% vs62.20%,44.50% vs0%, respectively (log-rank test,χ2=0.710, P=0.399), there was no significant difference between the two groups;
The OS and DFS rates in TCM-IT patients were higher compared with ITO patients, and the difference was significant (P＜0.05)
The OS rates in TCMO patients were higher compared with SO patients, and the difference was significant (P＜0.05),While the difference between the TCMO and SO patients was not significant (P>0.05)
The overall median survival time was 151.20 months (TCM-IT),43.87 months (ITO), and 20.77 months (SO). While the survival rates of TCMO group were higher than 50%, the median survival time of the TCMO group can not be calculated.
The median DFS times were 152.900 months (TCMO),51.733 months (ITO), and 76.667 months (SO), respectively.The median DFS times of the SO and TCMO groups were both longer than the median DFS times of the ITO, the median survival time of the TCM-IT group can not be calculated.
The 1-,2-,3-, and 5-year recurrence rates in patients with TCMO group and the ITO groupwere 15% and 19%,5% and 10%,4% and 12%, and 5% and 4%, respectively; the difference was significant (P=0.002).
Univariate analysis for OS were calculated for patient showed the significant prognostic factors were family history, globulin, tumor number, vascular invasion, tumor location, Child-Pugh classification, TNM staging, and therapy mode (P< 0.05).Multivariate survival analysis by Cox proportional hazard model, the six independent factors were as follows:therapy mode, tumor size, seeking behavior, TNM staging, family history, sex. Results of the multivariate survival analysis also showed group 2 (so group versus ITO group), tumor size, TNM staging, and family history were major risk factors of recurrence for small HCC tumors (P< 0.05, regression coefficient>0, relative risk 2.613,1.210,1.365,2.104), while seeking behavior, sex, the group 1(TCMO group versus ITO group) and group 3 (TCM-IT group vs ITO group) using different therapy mode were protective factors (P<0.05, regression coefficient<0, relative risk 0.659,0.431, 0.210,0.294).The results showed that the risk of death from HCC in ITO was 4.76 times and 3.40 times higer than the TCMO and TCMO-ITgroup.
Univariate analysis for DFS were performed on the patients with different group,and results showed the significant prognostic factors (P<0.05)including age, AFP,Tumor capsule,TNM staging, therapy mode.Multivariate survival analysis showed the two independent factors were therapy mode and TNM staging. Results of the multivariate survival analysis also showed group 1(TCMO versus ITO group) was major protective factor of recurrence for small HCC tumors (P=0.002,HR=0.518,95%CL0.341-0.788), The results of the multivariate survival analysis showed that the risk of recurrence in ITO patients was 1.93 times than in TCMO patients. While group 2 (SO group versus ITO group)was major risk factor, the risk of recurrence in SO patients was 1.107 times than in ITO. While Group3 (TCM-IT group vs ITO group) was the protective factor (P=0.001,HR= 0.401,95%CL0.233-0.690), showed that the risk of recurrence of IT group was 2.49 than TCM-IT group.
Conclusions:
Long-term oral use of ruanganfang (RGF) (originally named ruanjianhugan tablets) can improve significantly DFS and OS for small-HCC after resection compared with interventional therapy. Randomized, controlled trials are needed to confirm the findings of this study.
引文
[1]、中国抗癌协会肝癌专业委员会.原发性肝癌的临床诊断与分期标准[J].中华肝脏病杂志,2001,9(6):324.
[2]、李佩文.肿瘤学.中国中医药出版社.1996,740.
[3]、陈湘君,金实,周亚滨.中医内科学.上海科学技术出版社.2004:241.
[4]、肖开银.原发性肝癌流行病学研究进展[J].中国普外基础与临床杂志.2000,7(4):272.
[5]、汤钊猷.现代肿瘤学.复旦大学出版社.2003,738-741.
[6]、管冬元,方肇勤.上海中医药大学学报.健脾理气法防治肝癌的研究进展.2005,19(2):60-63.
[7]、金实.李春婷.疑难病中医治疗研究.人民卫生出版社.2006,203.
[8]、刘庆,岳小强,候风刚,顾伟等.血瘀证与肝癌关系浅析.山东中医药大学学报.2003,27(2):92-94.
[9]、凌昌全.“癌毒”是恶性肿瘤之本.中西医结合学报,2008,6(2):111-114.
[10]、梁水庭,陆云飞,黎乐群,林进令,巫山,廖清华,李艳宁,卢月华.肝癌二级预防与早期发现和预后评价的研究.广西医科大学学报.1997,14(4):2.
[11]、梁水庭,巫山,林进令,黎乐群,陆云飞,廖清华,苏翼联.软坚护肝片的护肝及抗乙肝病毒作用的实验研究.中医药研究.1997,13(3):50.
[12]、梁水庭,覃晓,黎乐群,等.软坚护肝片及甘草甜素片对肝癌术后复发的干预性研究[J].临床肝胆病杂志.2004,20(5):293-294.
[13]、郭庆渠,梁水庭,梁雪婧,等.软坚护肝片预防肝纤维化形成的实验研究[J].广西医科大学学报.2007,24(2)：261-263.
[14]、翁维良,房书亭.临床中药学.河南科学技术出版社.2001.431.
[15]、杜士明,周本宏,杨光义.山豆根水提物抗炎作用研究.中国药房.2008年19(18):1371-1372.
[16]、丁风荣,卢炜,邱世翠,等.山豆根体外抑菌作用研究[J].时珍国医国药,2002,13(6):335-336.
[17]、赵培荣,田爱琴,马湘玲,等.山豆根对人食管癌细胞株(Eca.109)杀伤、抑制及脱氢酶类影响[J].河南肿瘤学杂志,1998,11(2):87-89.
[18]、肖正明,宋景贵,徐朝晖,等.山豆根水提物对体外培养人肝癌细胞增殖及代射的影响[J].山东中医药大学学报,2000,24(1):62-64.
[19]、姚仲青,朱虹,王光凤.山豆根总生物碱抗肿瘤作用的初步研究[J].南京中医药大学学报,2005,21(4):253-254.
[20]、张良,张万峰,王日芝,等.复方山豆根注射液对茶瘤小鼠B-(16)、lewis抑瘤作用的实验研究[J].中医药信息,2001,18(6):53.
[21]、崔爱玲,范天利,张娴.高精度胸腺肽与山豆根治疗慢性乙肝疗效观察[J].临床肝胆病杂志,1997,13(4):221.
[22]、王放银,段林东,赵良忠.夏枯草抗菌成分的提取及其抗菌效果的研究[J].西南农业大学学报(自然科学版),2004,26(6):773-775.
[23]、中国药科大学.中药辞海：第2卷[Z].北京：中同医药科技出版社,1995.2022-2025.
[24]、Kagevama S.Kurokawa M,Shiraki K.Extract of Prunella vulgaris spikes inhibits HIV replicationat reversetran scription in vitro and can be absorbedfrom intestine in
vivo[J].Antivi-CHem-Chemother,2000,11 (2):157.
[25]、Xu HX,Lee SH,Lee SF.et al,Isolation and charac-terization of an anti HSV polysaccharide from Prunella vulgaris[J].Antiviral Res,1999,44(1):43.
[26]、周新颖.夏枯草粗提物抑制乳腺癌细胞增殖和逆转耐药的作用与机制初探.中国医科大学硕士学位论文,沈阳：中国医科大学,2006:7-18.
[27]、王琨,董惠芳,章晓鹰,等.夏枯草对SGC-7901细胞的影响.上海医学检验杂志,2000,15(5):305-307.
[28]、马丽萍,赵培荣,田爱琴,等.夏枯草对Eca109细胞的影响.肿瘤基础与临床,2006,119(13)：199--200.
[29]、董杰德.四种中草药抗柯萨奇及埃柯病毒的实验研究[J].山东中医学院学报,1993,17(4):46.
[30]、王卫华.虎杖提取液抗柯萨奇病毒B3的实验研究[J].湖北中医杂志,2001,23(9):47-48.
[31]、中国中医研究院中药研究所病毒组.中草药对呼吸道病毒致细胞病变作用的影响[J].新医药学杂志,1973,(1):26.
[32]、王志洁.虎杖中蒽醌化合物部分分离品抗Ⅰ型人疱疹病毒的实验研究[J].山东中医药大学学报,1998,22(6):458.
[33]、唐望先,虞涤霞,但自力,等.肝炎平对急性肝损害时脂质过氧化作用的实验研究[J].同济医科大学学报.1998,27(1):56.
[34]、Bhat KP,Pezzuto JM.Cancer chemopreventive activity of resveratrol[J].Ann NY Acad Sci,2002,957(3):210
[35]、Niles RM.McFardand M,Weimer MB.Et al.Resveratroisa potent inducer of apoptosis in human melanoma cells[J].Cancer Lett,2003,190(2):157.
[36]、赵铁华,高巍,杨鹤松等.黄芩茎叶总黄酮抗炎作用的实验研究[J].中国中医药科技.2001,8(3)：174.
[37]、杨得坡,胡海燕,黄世亮.黄芩甙元和黄苓甙对皮肤真菌与细菌抑制作用的研究[J].中药材.2000,25(5):272--274.
[38]、蒋锡源,杨珍珠,胡志军,等.50种治疗肝炎中草药与制剂体外抑制活性的比较[J].现代应用药学,1992,9(5):208--211.
[39].Okita K,Li Q,Murakamio T,et al.Anti-growth effects with components of Sho-saiko-to(TJ-9)on cultured human hepatoma cells[J].Eur J Cancer Prev,1993,2(2):169.
[40]、侯华新,黎丹戎,秦箐,等.黄芩黄酮A对人肝癌细胞7402的抑制能力及体外增效作用[J].中国临床药学杂志,2000,9(3)：166-168.
[41]、翟学敏,和水祥,任牡丹,等.丹参酮ⅡA对人肝癌SMMC-7721细胞EGF及其受体表达的影响[J].浙江大学学报：医学版.2009,38(2)：163-169.
[42]、符寒,和水祥,徐俊丽,丹参酮ⅡA对肝癌细胞血管内皮生长因子表达的影响[J].西安交通大学学报：医学版.2009,30(1)：115-118.
[43]、陈小桃,古辉,陈叙波,黄锦华.丹参对肝硬化上消化道大出血患者肝功能保护作用的临床研究.[J]中国医师杂志.2007,9(7):989-990.
[44]、郭俊.张雷.曾柱,等.复方丹参滴丸对高脂血症狗血液流变学影响的研究.中国血液流变学杂志.2004.14(1)：1.[45]、刘川,王淳,刘平,等.三七三醇皂苷治疗脑梗塞116例疗效分析[J].成都中医药大学学报,2007,30(1):6-7.
[46]、余万桂,张恒文,晏年春,等.三七总皂苷对肝纤维化小鼠血清酶学及NO的影响[J].中药药理与临床,2005,21(5)22-24.
[47]、木孝夫.生三七对四氯二苯二氧化物所致损害的抑制作用[J].国外医学中医中药分册,1997,19(1):29-31.
[48]、秦红霖,高月.女贞子化学成分及药理研究进展[J].2007,18(1):84-85.
[49]、蔡立明.女贞子药理作用及其临床应用[J].时珍国医国药,2000,11(5)：474.
[50]、张子臻.女贞子能降血糖、改善心肌供血[J].中医杂志,1998,39(9)：518.
[51].Takata R, Yamamoto R,Yanai T,et al. Immuno-stimulatory effects of a polysaccharide-rich substance with antitumor activity isolatedfrom black currant[J]. B iosci B iotechnol B iochem, 2005,69(11):2042-50.
[52]、JiY B, JiC F, Zou X,et al.Study on the effects of two kinds of cactus polysaccharide on erythrocyte membrane p rotein and fluidity of the lip id in S180 mice [J].China J Chin Mat Med,2004,29(10):967-70.
[53]、JiY B, JiC F, Zou X,et al.Study on the effects of two kinds of cactus polysaccharide on erythrocyte membrane p rotein and fluidity of the lip id in S180 mice [J]. China J Chin Mat Med,2004,29(10):967-70.
[54]、Feng G,Luo L Q, Kong Q Z, et al. Study of the cell apoptosis and mechanism of plant polysaccharide in cellular signalling pathway[J]. Cancer Res Prevent Treat,2005,32(9):557-9.
[55]、张小梅.黄芪多糖的免疫调节作用及抗肿瘤作用研究进展[J].大连学报,2003,24(6)101-3.
[56]、时维静,李立顺,乐其新,等.黄芪三种活性成分的提取与分离[J].中兽医医药杂志.2007,(5):37-39.
[57]、黄宏思,黄卫彤,韦鹏涯.黄芪多糖协同抗癌药物对肿瘤细胞的杀伤作用[J].中国现代临床医学杂志,2007,6(4)：1-2.
[58]、许杜娟,陈敏珠.黄芪多糖的抑瘤作用及其机制[J].中国医院药学杂志,2005,25(10):923-925.
[59]、朱金照,等115味中药促胃肠动力作用的筛选研究[J].第三军医大学学报,2000,22(5):436;8.
[60]、朱金照,等.砂仁对大鼠胃肠运动及神经递质的影响.中国中西医结合消化杂志,2001,9(4)：205).
[61]、邱赛红,等.芳香化湿药开胃作用机理的实验研究[J].中药药理与临床,1995,11(4):24.
[62]、王红武,等.砂仁对消化系统药理作用的实验研究[J].中国中医药科技,1997,4(5):284.
[63]、张明发,等.辛温(热)合归脾胃经中药药性研究(1)利胆作用[J].中国中医基础医学杂志,1998,4(8)：16.
[64]日本东洋医学会杂志,1953,3(2)：57.
[65]、吴师竹.砂仁对血小板聚集功能的影响[J].中药药理与临床,1990,6(5):32.
[66]、昌喜涛,马金荣,尹尔丽.山楂叶总黄酮对大鼠脑缺血再灌注损伤的保护作用[J].中外健康文摘临床医药版,2007,4(10):5-6.
[67]、崔太昌.山楂提取物对环磷酰胺致小鼠精子畸变的抑制作用[J].中国公共卫生,2002:266-2661.
[68]、权迎春,关丽萍.山楂叶提取物的抗炎与镇痛作用研究[J].时珍国医国药,2006,17(4):556-557.
[69]、林玲.山楂液杀灭微生物作用及其影响因素的试验观察[J].中国消毒学杂志,2000,17(2):85-87.
[70]、沈映君.中药药理学[M].北京：人民卫生出版社,2000:574-578.
[71]、彭芝配.山楂醇提液的实验研究[J].中医药信息,1983,(3):32-32.
[72]、汤钊猷.现代肿瘤学.复旦大学出版社.2003.738-741.
[73]、唐友庆,李国材,朱少立.性别与原发性肝癌预后的关系.广东医学,1990,11(6):4-6.
[74]、杨秉辉,夏景林,黄力文,等.我国肝癌“临床相”30年的变迁-原发性肝癌3250例的对比研究.中华医学杂志.2003;83(12)：1053-1057..
[75]、Lam CM, Yong JL, Chan AO, et al. Better survival in female patients with hepatocellular carcinoma:oral contraceptive pills related[J]. J Clin Gastroenterol,2005,39(6):533-539.
[76]、褚光平,蔡敬铭,刘强,肖亿.青年人原发性肝癌的治疗与预后分析[J].中国肿瘤临床.2005,32(22)：1299.
[77]、肖开银,黎乐群,彭民浩.家族聚集性肝癌101例家族史和临床分析[J].医科大学学报.2005,22(2):224-226.
[78]、梁水庭,陆云飞,黎乐群,林进令,巫山,廖清华,李艳宁,卢月华.肝癌二级预防与早期发现和预后评价的研究.广西医科大学学报[J].1997,14(4):28.
[79]、Nouso K,Kobayashi Y,Nakamura S,Kobayashi S.et al. Evolution of prognostic factors in hepatocellular carcinoma in Japan. Aliment Pharmacol Ther.2010,31(3):407-414.
[80]、Vora SR,Zheng H,Stadler ZK,Fuchs CS,Zhu AX. Serum alpha-fetoprotein response as a surrogate for clinical outcome in patients receiving systemic therapy for advanced hepatocellular carcinoma. Oncologist.2009,14(7):717-725.
[81].Kondo K,Chijiiwa K,Kai M,Otani K,et al. Surgical strategy for hepatocellular carcinoma patients with portal vein tumor thrombus based on prognostic factors. J Gastrointest Surg. 2009,13(6):1078-1083..
[82]、李凌,饶荣生,牛佳木,陈丽,万会平.原发性肝癌预后的相关因素分析.肿瘤防治杂志[J]).2003,10(12)：1320-1321.
[83]、Wan Yee Lau,Eric C.H.Lai. Hepatocellular carcinoma:current management and recent advances. Hepatobiliary Pancreat Dis Int,7(3):237.
[84]、周信达,汤钊猷,余业勤,杨秉辉,张博恒.影响肝癌预后的有关因素分析[J].中华内科杂志.1996,35(8):527.
[85]、周信达,汤钊猷,杨秉辉,林芷英等.1000例小肝癌手术切除经验[J].中国实用外科杂志.2001,21(1)：41.
[86]、汤钊猷.现代肿瘤学.复旦大学出版社:2003,751.
[87]、张百红,贺佳,朱德增,陈哲,等.一个新的肝癌分期系统的构建[J].第三军医大学学报.2006,28(3):253.
[88]、乔雁翔,曾麟,曾文铤,梁建新.分期系统在中、晚期肝癌生存关系的评价.临床医学工程.2009,16(8):62-63.
[89]、汤钊猷.小肝癌研究展望[J].医学临床研究2003,20(9):643.
[90]、Fan J.Lin ZY.Ma ZC, et al.Experience of 1000 patients who underwent hepatectomy for small hepatocellular carcinoma.Cancer.2001;91 (8):1479-86.
[91]、Chen SJ. Chen Z. Liang Y,etal.Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia. Proceedings of the National Academy of Sciences of the United States ofAmerica.2008;105(12):4826-31.
[92]、Efferth T.Kaina B.Konkimalla VS,et al. From traditional Chinese medicine to rational cancer therapy. Trends in molecular medicine.2007;13(8):353-61.
[93]、Hui EK.Hui KK. Johnston MF.The potential of a person-centered approach in caring for patients with cancer:a perspective from the UCLA center for East-West medicine. Integrative cancer therapies.2006;5(1):56-62.
[94]、Zhe Chen, Bai Li, Xiaoqiang Yue,etal,. The Journal of Alternative and Complementary Medicine. December 2006,12(10):941-942.
[95]、Lau WY. Primary hepatocellular carcinoma. In:Blumgart LH & Fong Y (2nd eds). Surgery of The Liver and BiliaryTract Volume Ⅱ, W. B. Saunders London; 2000:1423-1450.
[96]、Lau WY. Primary liver tumors. Semin Surg Oncol 2000;19:135-144.
[97]、Lau WY. Management of hepatocellular carcinoma. J R CollSurg Edinb 2002;47:389-399.
[98]、Lai EC, Lau WY. The continuing challenge of hepatic cancerin Asia. Surgeon 2005;3:210-215.
[99]、Shi M, Zhang CQ, Zhang YQ, Liang XM, Li JQ.Micrometastases of solitary hepatocellular carcinoma and appropriate resection margin. World J Surg 2004;28:376-381.
[100]、Wong IH, Yeo W, Leung T, Lau WY, Johnson PJ.Circulating tumor cell mRNAs in peripheral blood from hepatocellular carcinoma patients under radiotherapy,surgical resection or chemotherapy:a quantitative evaluation. Cancer Lett 2001; 167:183-191.
[101]、Wong IH, Lau WY, Leung T, Yeo W, Johnson PJ.Hematogenous dissemination of hepatocytes and tumor cells after surgical resection of hepatocellular carcinoma:aquantitative analysis. Clin Cancer Res 1999;5:4021-4027.
[102]、中国抗癌协会肝癌专业委员会,中国抗癌协会临床肿瘤学协作专业委员会,中华医学会肝病学分会肝癌学组.原发性肝癌规范化诊治的专家共识[J].肿瘤.2009,29(4):299-300
[103]、Wu CC, Ho YZ, Ho WL, et al. Preoperative transcatheter arterial chemoembolization for resectable large hepatocellular carcinoma:a reappraisal. Br J Surg.1995;82:122-126..
[104]、Llovet JM, Bruix J. Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol 2008; 48:S20-37.
[105]、褚光平,蔡敬铭,刘强,肖亿.青年人原发性肝癌的治疗与预后分析[J].中国肿瘤临床.2005,32(22)：1299.
[106]、吴育连,苏昆仑,董鑫等.肝癌切除术后早／晚期复发的危险因素与治疗[J].中华肝胆外科杂志,2006,,12(6):370.
[107]、Peng SY,Chen WJ,Lai PL,et al.High a-fetoprotein level correlates with high stage,early recurrence and poor progn osis ofhepatocellular carcinoma:sign ificance of hepatitis virus infection,age,p53 and catenin mutations.Int J Cancer,2004,112:44-50.
[108]、Tanaka T,Yamanaka N,Oriyama T,et al.Factors regulating tumor pressure in hepatocelluar carcinoma and implications for tumor spread.Hepatology,1997,26:283.
[109]、Tanaka K,Shimada H,Matsuo K,et al. Clinical features of hepatocellular carcinoma developing extrahepatic recurrences after curative resection. World J Surg.2008,32(8):1738-1747.
[110]、Sasaki Y,Yamada T,Tanaka H,et al. Risk of recurrence in a long-term follow-up after surgery in 417 patients with hepatitis B-or hepatitis C-related hepatocellular carcinoma. Ann Surg. 2006,244(5):771-780.
[1]Parkin DM, Bray F,Ferlay J, Pisani P. Global cancer statistics 2002.CA Cancer J Clin.2005;55:74-108.
[2]钦伦秀,孙惠川,汤钊猷.原发性肝癌研究进展-2006沪港国际肝病大会纪要[J].中华外科杂志2006,44(15):1070.
[3]周阿高,张勇,蒉纲,等.不同治法中药复方对H22肝癌小鼠瘤质量和体质量及免疫功能的影响[J].中西医结合学报,2008,6(1):77.
[4]王昌俊,刘友章,许鑫梅.健脾化瘀复方药物血清对人肝癌细胞BEL7402增殖的影响[J].中医药通报,2006,5(3):54-56.
[5]谭宇蕙,吴映雅,王慧峰,等.纯中药复方消癌根含药血清对小鼠肝癌细胞H22的作用研究.医疗保健器具.2005,6:69.
[6]张建武,杨旭波,唐建平,等。复方斑蝥注射液对人肝癌细胞SMMC-7721的生长抑制作用.中国民族民间医药.2009:8-9.
[7]王玉琴,张伟,李锋,顾锦华.复方龙葵胶囊对2-乙酰氨基芴诱导大鼠肝癌的影响.中国交通医学杂志.2006,20(2)：131-132.
[8]鲁玉辉,符林春.叶下珠复方对人肝癌HePG2细胞体外增殖抑制及诱导凋亡作用.中药新药与临床药理,2007,18(3)：183-184.
[9]陈志奎,林礼务,王艳,等.超声介入复方中药"99-克星”活性组分诱导肝癌细胞凋亡及机制[J].中国医学影像技术.2006,22(12):1792.
[10]曹永艳,王猛,黄开顺,等.复方斑蝥胶囊血清诱导人肝癌SMMC-7721细胞蛋白质组差异表达分析[J].中国中药杂志.2007,32(9):831-833.
[11]杨军,丁敏,张太君,等.复方斑蝥胶囊抑制人肝癌细胞SMMC-7721的增殖和诱导凋亡的实验
[30]郭庆渠,梁水庭,梁雪婧,等.软坚护肝片预防肝纤维化形成的实验研究[J].广西医科大学学报.2007,24(2)：261-263.
[31]叶健,徐锡坤,周建伟,等.复方半枝莲防治二乙基亚硝胺诱发大鼠肝癌的研究.中国中西医结合消化杂志.2002,10(2):67.
[32]袁冬生,王新华,李常青,肖会泉.复方肝癌宁抗乙型肝炎病毒的体外实验研究.世界华人消化杂志.2004,12(6):1292-1294.
[33]龙爱华,聂广.抑癌复方对大鼠肝癌前病变的抑制作用.中国癌症杂志.1999,9(5)：463.
[34]李应树,李军.“复方抗癌散”治疗中晚期肝癌的体会.中国民族民间医药杂志.1999,40:254.
[35]田义洲,李虹,黄立萍,张凌燕,石惠燕.艾迪注射液联合中药复方治疗晚期原发性肝癌30例.肿瘤学杂志,2009,15(1):86-86.
[36]吴洪斌,程琳,孟志强.复方党参白术颗粒对原发性肝癌治疗的疗效观察.中国医院用药评价与分析.2009,9(3):218-220.
[37]Yu Y,Lang QB,Chen Z, et al. The efficacy for unresectable Hepatocellular Carcinoma maybe improved by transcatheter arterial chemoembolization in combination with a traditional Chinese herbal medicine formula. Cancer.2009;115:5132-38.
[38]滕红丽,李硅,钟鸣,余胜民.复方红豆杉胶囊治疗肝癌60例临床研究.中医杂志,2006,47(4):277.
[39]任中海,张成辉,刘玉芝,韩东景FUdR,复方丹参联合苦参碱类治疗晚期原发性肝癌.中国肿瘤临床与康复.2002,9(6)：113.
[40]曲震,史彦芬,王义善.HLF方案合并复方斑蝥胶囊治疗原发性肝癌30例近期疗效观察.中国中医药科技.2002,9(6):336.
[41]徐虎.复方斑蝥胶囊对晚期原发性肝癌生存率的影响.湖北中医杂志.2009,31(4):23
[42]李秋,陈红,张孟瑜.复方斑蟊胶囊联合肝动脉化疗栓塞治疗中晚期肝癌.中国中西医结合外科杂志.2005,11(2)：130-131.
[43]梁启廉,陈小东,李小英,等.复方丹参滴丸加化疗治疗肝癌的临床疗效评价.中医药学刊.2006,24(1)：185-187.
[44]姜德清,立全晰,丁汇清.复方丹参经脐静脉置管门静脉灌注防治肝癌复发的临床研究.实用癌症杂志.2007,22(4):365.
[45]黄智芬,韦劲松,谭志强,等.复方丹参注射液加多巴胺速尿治疗肝癌腹水临床观察.中西医结合肝病杂志.2001,11(1):3-4.
[46]施华平,周玲玲.复方莪术油微球肝动脉栓塞对大鼠移植性肝癌的治疗作用.上海中医药大学学报.23(5):58-60.
[47]邹玺,刘宝瑞,钱晓萍.中医药治疗肿瘤的疗效评价标准的探讨.南京中医药大学学报,2005,21(4):270-271.
[48]Chen SJ. Chen Z. Liang Y,etal.Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia. Proceedings of the National Academy of Sciences of the United States of America.2008; 105(12):4826-31.
[2]、李佩文.肿瘤学.中国中医药出版社.1996,740.
[3]、陈湘君,金实,周亚滨.中医内科学.上海科学技术出版社.2004:241.
[4]、肖开银.原发性肝癌流行病学研究进展[J].中国普外基础与临床杂志.2000,7(4):272.
[5]、汤钊猷.现代肿瘤学.复旦大学出版社.2003,738-741.
[6]、管冬元,方肇勤.上海中医药大学学报.健脾理气法防治肝癌的研究进展.2005,19(2):60-63.
[7]、金实.李春婷.疑难病中医治疗研究.人民卫生出版社.2006,203.
[8]、刘庆,岳小强,候风刚,顾伟等.血瘀证与肝癌关系浅析.山东中医药大学学报.2003,27(2):92-94.
[9]、凌昌全.“癌毒”是恶性肿瘤之本.中西医结合学报,2008,6(2):111-114.
[10]、梁水庭,陆云飞,黎乐群,林进令,巫山,廖清华,李艳宁,卢月华.肝癌二级预防与早期发现和预后评价的研究.广西医科大学学报.1997,14(4):2.
[11]、梁水庭,巫山,林进令,黎乐群,陆云飞,廖清华,苏翼联.软坚护肝片的护肝及抗乙肝病毒作用的实验研究.中医药研究.1997,13(3):50.
[12]、梁水庭,覃晓,黎乐群,等.软坚护肝片及甘草甜素片对肝癌术后复发的干预性研究[J].临床肝胆病杂志.2004,20(5):293-294.
[13]、郭庆渠,梁水庭,梁雪婧,等.软坚护肝片预防肝纤维化形成的实验研究[J].广西医科大学学报.2007,24(2)：261-263.
[14]、翁维良,房书亭.临床中药学.河南科学技术出版社.2001.431.
[15]、杜士明,周本宏,杨光义.山豆根水提物抗炎作用研究.中国药房.2008年19(18):1371-1372.
[16]、丁风荣,卢炜,邱世翠,等.山豆根体外抑菌作用研究[J].时珍国医国药,2002,13(6):335-336.
[17]、赵培荣,田爱琴,马湘玲,等.山豆根对人食管癌细胞株(Eca.109)杀伤、抑制及脱氢酶类影响[J].河南肿瘤学杂志,1998,11(2):87-89.
[18]、肖正明,宋景贵,徐朝晖,等.山豆根水提物对体外培养人肝癌细胞增殖及代射的影响[J].山东中医药大学学报,2000,24(1):62-64.
[19]、姚仲青,朱虹,王光凤.山豆根总生物碱抗肿瘤作用的初步研究[J].南京中医药大学学报,2005,21(4):253-254.
[20]、张良,张万峰,王日芝,等.复方山豆根注射液对茶瘤小鼠B-(16)、lewis抑瘤作用的实验研究[J].中医药信息,2001,18(6):53.
[21]、崔爱玲,范天利,张娴.高精度胸腺肽与山豆根治疗慢性乙肝疗效观察[J].临床肝胆病杂志,1997,13(4):221.
[22]、王放银,段林东,赵良忠.夏枯草抗菌成分的提取及其抗菌效果的研究[J].西南农业大学学报(自然科学版),2004,26(6):773-775.
[23]、中国药科大学.中药辞海：第2卷[Z].北京：中同医药科技出版社,1995.2022-2025.
[24]、Kagevama S.Kurokawa M,Shiraki K.Extract of Prunella vulgaris spikes inhibits HIV replicationat reversetran scription in vitro and can be absorbedfrom intestine in
vivo[J].Antivi-CHem-Chemother,2000,11 (2):157.
[25]、Xu HX,Lee SH,Lee SF.et al,Isolation and charac-terization of an anti HSV polysaccharide from Prunella vulgaris[J].Antiviral Res,1999,44(1):43.
[26]、周新颖.夏枯草粗提物抑制乳腺癌细胞增殖和逆转耐药的作用与机制初探.中国医科大学硕士学位论文,沈阳：中国医科大学,2006:7-18.
[27]、王琨,董惠芳,章晓鹰,等.夏枯草对SGC-7901细胞的影响.上海医学检验杂志,2000,15(5):305-307.
[28]、马丽萍,赵培荣,田爱琴,等.夏枯草对Eca109细胞的影响.肿瘤基础与临床,2006,119(13)：199--200.
[29]、董杰德.四种中草药抗柯萨奇及埃柯病毒的实验研究[J].山东中医学院学报,1993,17(4):46.
[30]、王卫华.虎杖提取液抗柯萨奇病毒B3的实验研究[J].湖北中医杂志,2001,23(9):47-48.
[31]、中国中医研究院中药研究所病毒组.中草药对呼吸道病毒致细胞病变作用的影响[J].新医药学杂志,1973,(1):26.
[32]、王志洁.虎杖中蒽醌化合物部分分离品抗Ⅰ型人疱疹病毒的实验研究[J].山东中医药大学学报,1998,22(6):458.
[33]、唐望先,虞涤霞,但自力,等.肝炎平对急性肝损害时脂质过氧化作用的实验研究[J].同济医科大学学报.1998,27(1):56.
[34]、Bhat KP,Pezzuto JM.Cancer chemopreventive activity of resveratrol[J].Ann NY Acad Sci,2002,957(3):210
[35]、Niles RM.McFardand M,Weimer MB.Et al.Resveratroisa potent inducer of apoptosis in human melanoma cells[J].Cancer Lett,2003,190(2):157.
[36]、赵铁华,高巍,杨鹤松等.黄芩茎叶总黄酮抗炎作用的实验研究[J].中国中医药科技.2001,8(3)：174.
[37]、杨得坡,胡海燕,黄世亮.黄芩甙元和黄苓甙对皮肤真菌与细菌抑制作用的研究[J].中药材.2000,25(5):272--274.
[38]、蒋锡源,杨珍珠,胡志军,等.50种治疗肝炎中草药与制剂体外抑制活性的比较[J].现代应用药学,1992,9(5):208--211.
[39].Okita K,Li Q,Murakamio T,et al.Anti-growth effects with components of Sho-saiko-to(TJ-9)on cultured human hepatoma cells[J].Eur J Cancer Prev,1993,2(2):169.
[40]、侯华新,黎丹戎,秦箐,等.黄芩黄酮A对人肝癌细胞7402的抑制能力及体外增效作用[J].中国临床药学杂志,2000,9(3)：166-168.
[41]、翟学敏,和水祥,任牡丹,等.丹参酮ⅡA对人肝癌SMMC-7721细胞EGF及其受体表达的影响[J].浙江大学学报：医学版.2009,38(2)：163-169.
[42]、符寒,和水祥,徐俊丽,丹参酮ⅡA对肝癌细胞血管内皮生长因子表达的影响[J].西安交通大学学报：医学版.2009,30(1)：115-118.
[43]、陈小桃,古辉,陈叙波,黄锦华.丹参对肝硬化上消化道大出血患者肝功能保护作用的临床研究.[J]中国医师杂志.2007,9(7):989-990.
[44]、郭俊.张雷.曾柱,等.复方丹参滴丸对高脂血症狗血液流变学影响的研究.中国血液流变学杂志.2004.14(1)：1.[45]、刘川,王淳,刘平,等.三七三醇皂苷治疗脑梗塞116例疗效分析[J].成都中医药大学学报,2007,30(1):6-7.
[46]、余万桂,张恒文,晏年春,等.三七总皂苷对肝纤维化小鼠血清酶学及NO的影响[J].中药药理与临床,2005,21(5)22-24.
[47]、木孝夫.生三七对四氯二苯二氧化物所致损害的抑制作用[J].国外医学中医中药分册,1997,19(1):29-31.
[48]、秦红霖,高月.女贞子化学成分及药理研究进展[J].2007,18(1):84-85.
[49]、蔡立明.女贞子药理作用及其临床应用[J].时珍国医国药,2000,11(5)：474.
[50]、张子臻.女贞子能降血糖、改善心肌供血[J].中医杂志,1998,39(9)：518.
[51].Takata R, Yamamoto R,Yanai T,et al. Immuno-stimulatory effects of a polysaccharide-rich substance with antitumor activity isolatedfrom black currant[J]. B iosci B iotechnol B iochem, 2005,69(11):2042-50.
[52]、JiY B, JiC F, Zou X,et al.Study on the effects of two kinds of cactus polysaccharide on erythrocyte membrane p rotein and fluidity of the lip id in S180 mice [J].China J Chin Mat Med,2004,29(10):967-70.
[53]、JiY B, JiC F, Zou X,et al.Study on the effects of two kinds of cactus polysaccharide on erythrocyte membrane p rotein and fluidity of the lip id in S180 mice [J]. China J Chin Mat Med,2004,29(10):967-70.
[54]、Feng G,Luo L Q, Kong Q Z, et al. Study of the cell apoptosis and mechanism of plant polysaccharide in cellular signalling pathway[J]. Cancer Res Prevent Treat,2005,32(9):557-9.
[55]、张小梅.黄芪多糖的免疫调节作用及抗肿瘤作用研究进展[J].大连学报,2003,24(6)101-3.
[56]、时维静,李立顺,乐其新,等.黄芪三种活性成分的提取与分离[J].中兽医医药杂志.2007,(5):37-39.
[57]、黄宏思,黄卫彤,韦鹏涯.黄芪多糖协同抗癌药物对肿瘤细胞的杀伤作用[J].中国现代临床医学杂志,2007,6(4)：1-2.
[58]、许杜娟,陈敏珠.黄芪多糖的抑瘤作用及其机制[J].中国医院药学杂志,2005,25(10):923-925.
[59]、朱金照,等115味中药促胃肠动力作用的筛选研究[J].第三军医大学学报,2000,22(5):436;8.
[60]、朱金照,等.砂仁对大鼠胃肠运动及神经递质的影响.中国中西医结合消化杂志,2001,9(4)：205).
[61]、邱赛红,等.芳香化湿药开胃作用机理的实验研究[J].中药药理与临床,1995,11(4):24.
[62]、王红武,等.砂仁对消化系统药理作用的实验研究[J].中国中医药科技,1997,4(5):284.
[63]、张明发,等.辛温(热)合归脾胃经中药药性研究(1)利胆作用[J].中国中医基础医学杂志,1998,4(8)：16.
[64]日本东洋医学会杂志,1953,3(2)：57.
[65]、吴师竹.砂仁对血小板聚集功能的影响[J].中药药理与临床,1990,6(5):32.
[66]、昌喜涛,马金荣,尹尔丽.山楂叶总黄酮对大鼠脑缺血再灌注损伤的保护作用[J].中外健康文摘临床医药版,2007,4(10):5-6.
[67]、崔太昌.山楂提取物对环磷酰胺致小鼠精子畸变的抑制作用[J].中国公共卫生,2002:266-2661.
[68]、权迎春,关丽萍.山楂叶提取物的抗炎与镇痛作用研究[J].时珍国医国药,2006,17(4):556-557.
[69]、林玲.山楂液杀灭微生物作用及其影响因素的试验观察[J].中国消毒学杂志,2000,17(2):85-87.
[70]、沈映君.中药药理学[M].北京：人民卫生出版社,2000:574-578.
[71]、彭芝配.山楂醇提液的实验研究[J].中医药信息,1983,(3):32-32.
[72]、汤钊猷.现代肿瘤学.复旦大学出版社.2003.738-741.
[73]、唐友庆,李国材,朱少立.性别与原发性肝癌预后的关系.广东医学,1990,11(6):4-6.
[74]、杨秉辉,夏景林,黄力文,等.我国肝癌“临床相”30年的变迁-原发性肝癌3250例的对比研究.中华医学杂志.2003;83(12)：1053-1057..
[75]、Lam CM, Yong JL, Chan AO, et al. Better survival in female patients with hepatocellular carcinoma:oral contraceptive pills related[J]. J Clin Gastroenterol,2005,39(6):533-539.
[76]、褚光平,蔡敬铭,刘强,肖亿.青年人原发性肝癌的治疗与预后分析[J].中国肿瘤临床.2005,32(22)：1299.
[77]、肖开银,黎乐群,彭民浩.家族聚集性肝癌101例家族史和临床分析[J].医科大学学报.2005,22(2):224-226.
[78]、梁水庭,陆云飞,黎乐群,林进令,巫山,廖清华,李艳宁,卢月华.肝癌二级预防与早期发现和预后评价的研究.广西医科大学学报[J].1997,14(4):28.
[79]、Nouso K,Kobayashi Y,Nakamura S,Kobayashi S.et al. Evolution of prognostic factors in hepatocellular carcinoma in Japan. Aliment Pharmacol Ther.2010,31(3):407-414.
[80]、Vora SR,Zheng H,Stadler ZK,Fuchs CS,Zhu AX. Serum alpha-fetoprotein response as a surrogate for clinical outcome in patients receiving systemic therapy for advanced hepatocellular carcinoma. Oncologist.2009,14(7):717-725.
[81].Kondo K,Chijiiwa K,Kai M,Otani K,et al. Surgical strategy for hepatocellular carcinoma patients with portal vein tumor thrombus based on prognostic factors. J Gastrointest Surg. 2009,13(6):1078-1083..
[82]、李凌,饶荣生,牛佳木,陈丽,万会平.原发性肝癌预后的相关因素分析.肿瘤防治杂志[J]).2003,10(12)：1320-1321.
[83]、Wan Yee Lau,Eric C.H.Lai. Hepatocellular carcinoma:current management and recent advances. Hepatobiliary Pancreat Dis Int,7(3):237.
[84]、周信达,汤钊猷,余业勤,杨秉辉,张博恒.影响肝癌预后的有关因素分析[J].中华内科杂志.1996,35(8):527.
[85]、周信达,汤钊猷,杨秉辉,林芷英等.1000例小肝癌手术切除经验[J].中国实用外科杂志.2001,21(1)：41.
[86]、汤钊猷.现代肿瘤学.复旦大学出版社:2003,751.
[87]、张百红,贺佳,朱德增,陈哲,等.一个新的肝癌分期系统的构建[J].第三军医大学学报.2006,28(3):253.
[88]、乔雁翔,曾麟,曾文铤,梁建新.分期系统在中、晚期肝癌生存关系的评价.临床医学工程.2009,16(8):62-63.
[89]、汤钊猷.小肝癌研究展望[J].医学临床研究2003,20(9):643.
[90]、Fan J.Lin ZY.Ma ZC, et al.Experience of 1000 patients who underwent hepatectomy for small hepatocellular carcinoma.Cancer.2001;91 (8):1479-86.
[91]、Chen SJ. Chen Z. Liang Y,etal.Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia. Proceedings of the National Academy of Sciences of the United States ofAmerica.2008;105(12):4826-31.
[92]、Efferth T.Kaina B.Konkimalla VS,et al. From traditional Chinese medicine to rational cancer therapy. Trends in molecular medicine.2007;13(8):353-61.
[93]、Hui EK.Hui KK. Johnston MF.The potential of a person-centered approach in caring for patients with cancer:a perspective from the UCLA center for East-West medicine. Integrative cancer therapies.2006;5(1):56-62.
[94]、Zhe Chen, Bai Li, Xiaoqiang Yue,etal,. The Journal of Alternative and Complementary Medicine. December 2006,12(10):941-942.
[95]、Lau WY. Primary hepatocellular carcinoma. In:Blumgart LH & Fong Y (2nd eds). Surgery of The Liver and BiliaryTract Volume Ⅱ, W. B. Saunders London; 2000:1423-1450.
[96]、Lau WY. Primary liver tumors. Semin Surg Oncol 2000;19:135-144.
[97]、Lau WY. Management of hepatocellular carcinoma. J R CollSurg Edinb 2002;47:389-399.
[98]、Lai EC, Lau WY. The continuing challenge of hepatic cancerin Asia. Surgeon 2005;3:210-215.
[99]、Shi M, Zhang CQ, Zhang YQ, Liang XM, Li JQ.Micrometastases of solitary hepatocellular carcinoma and appropriate resection margin. World J Surg 2004;28:376-381.
[100]、Wong IH, Yeo W, Leung T, Lau WY, Johnson PJ.Circulating tumor cell mRNAs in peripheral blood from hepatocellular carcinoma patients under radiotherapy,surgical resection or chemotherapy:a quantitative evaluation. Cancer Lett 2001; 167:183-191.
[101]、Wong IH, Lau WY, Leung T, Yeo W, Johnson PJ.Hematogenous dissemination of hepatocytes and tumor cells after surgical resection of hepatocellular carcinoma:aquantitative analysis. Clin Cancer Res 1999;5:4021-4027.
[102]、中国抗癌协会肝癌专业委员会,中国抗癌协会临床肿瘤学协作专业委员会,中华医学会肝病学分会肝癌学组.原发性肝癌规范化诊治的专家共识[J].肿瘤.2009,29(4):299-300
[103]、Wu CC, Ho YZ, Ho WL, et al. Preoperative transcatheter arterial chemoembolization for resectable large hepatocellular carcinoma:a reappraisal. Br J Surg.1995;82:122-126..
[104]、Llovet JM, Bruix J. Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol 2008; 48:S20-37.
[105]、褚光平,蔡敬铭,刘强,肖亿.青年人原发性肝癌的治疗与预后分析[J].中国肿瘤临床.2005,32(22)：1299.
[106]、吴育连,苏昆仑,董鑫等.肝癌切除术后早／晚期复发的危险因素与治疗[J].中华肝胆外科杂志,2006,,12(6):370.
[107]、Peng SY,Chen WJ,Lai PL,et al.High a-fetoprotein level correlates with high stage,early recurrence and poor progn osis ofhepatocellular carcinoma:sign ificance of hepatitis virus infection,age,p53 and catenin mutations.Int J Cancer,2004,112:44-50.
[108]、Tanaka T,Yamanaka N,Oriyama T,et al.Factors regulating tumor pressure in hepatocelluar carcinoma and implications for tumor spread.Hepatology,1997,26:283.
[109]、Tanaka K,Shimada H,Matsuo K,et al. Clinical features of hepatocellular carcinoma developing extrahepatic recurrences after curative resection. World J Surg.2008,32(8):1738-1747.
[110]、Sasaki Y,Yamada T,Tanaka H,et al. Risk of recurrence in a long-term follow-up after surgery in 417 patients with hepatitis B-or hepatitis C-related hepatocellular carcinoma. Ann Surg. 2006,244(5):771-780.
[1]Parkin DM, Bray F,Ferlay J, Pisani P. Global cancer statistics 2002.CA Cancer J Clin.2005;55:74-108.
[2]钦伦秀,孙惠川,汤钊猷.原发性肝癌研究进展-2006沪港国际肝病大会纪要[J].中华外科杂志2006,44(15):1070.
[3]周阿高,张勇,蒉纲,等.不同治法中药复方对H22肝癌小鼠瘤质量和体质量及免疫功能的影响[J].中西医结合学报,2008,6(1):77.
[4]王昌俊,刘友章,许鑫梅.健脾化瘀复方药物血清对人肝癌细胞BEL7402增殖的影响[J].中医药通报,2006,5(3):54-56.
[5]谭宇蕙,吴映雅,王慧峰,等.纯中药复方消癌根含药血清对小鼠肝癌细胞H22的作用研究.医疗保健器具.2005,6:69.
[6]张建武,杨旭波,唐建平,等。复方斑蝥注射液对人肝癌细胞SMMC-7721的生长抑制作用.中国民族民间医药.2009:8-9.
[7]王玉琴,张伟,李锋,顾锦华.复方龙葵胶囊对2-乙酰氨基芴诱导大鼠肝癌的影响.中国交通医学杂志.2006,20(2)：131-132.
[8]鲁玉辉,符林春.叶下珠复方对人肝癌HePG2细胞体外增殖抑制及诱导凋亡作用.中药新药与临床药理,2007,18(3)：183-184.
[9]陈志奎,林礼务,王艳,等.超声介入复方中药"99-克星”活性组分诱导肝癌细胞凋亡及机制[J].中国医学影像技术.2006,22(12):1792.
[10]曹永艳,王猛,黄开顺,等.复方斑蝥胶囊血清诱导人肝癌SMMC-7721细胞蛋白质组差异表达分析[J].中国中药杂志.2007,32(9):831-833.
[11]杨军,丁敏,张太君,等.复方斑蝥胶囊抑制人肝癌细胞SMMC-7721的增殖和诱导凋亡的实验
[30]郭庆渠,梁水庭,梁雪婧,等.软坚护肝片预防肝纤维化形成的实验研究[J].广西医科大学学报.2007,24(2)：261-263.
[31]叶健,徐锡坤,周建伟,等.复方半枝莲防治二乙基亚硝胺诱发大鼠肝癌的研究.中国中西医结合消化杂志.2002,10(2):67.
[32]袁冬生,王新华,李常青,肖会泉.复方肝癌宁抗乙型肝炎病毒的体外实验研究.世界华人消化杂志.2004,12(6):1292-1294.
[33]龙爱华,聂广.抑癌复方对大鼠肝癌前病变的抑制作用.中国癌症杂志.1999,9(5)：463.
[34]李应树,李军.“复方抗癌散”治疗中晚期肝癌的体会.中国民族民间医药杂志.1999,40:254.
[35]田义洲,李虹,黄立萍,张凌燕,石惠燕.艾迪注射液联合中药复方治疗晚期原发性肝癌30例.肿瘤学杂志,2009,15(1):86-86.
[36]吴洪斌,程琳,孟志强.复方党参白术颗粒对原发性肝癌治疗的疗效观察.中国医院用药评价与分析.2009,9(3):218-220.
[37]Yu Y,Lang QB,Chen Z, et al. The efficacy for unresectable Hepatocellular Carcinoma maybe improved by transcatheter arterial chemoembolization in combination with a traditional Chinese herbal medicine formula. Cancer.2009;115:5132-38.
[38]滕红丽,李硅,钟鸣,余胜民.复方红豆杉胶囊治疗肝癌60例临床研究.中医杂志,2006,47(4):277.
[39]任中海,张成辉,刘玉芝,韩东景FUdR,复方丹参联合苦参碱类治疗晚期原发性肝癌.中国肿瘤临床与康复.2002,9(6)：113.
[40]曲震,史彦芬,王义善.HLF方案合并复方斑蝥胶囊治疗原发性肝癌30例近期疗效观察.中国中医药科技.2002,9(6):336.
[41]徐虎.复方斑蝥胶囊对晚期原发性肝癌生存率的影响.湖北中医杂志.2009,31(4):23
[42]李秋,陈红,张孟瑜.复方斑蟊胶囊联合肝动脉化疗栓塞治疗中晚期肝癌.中国中西医结合外科杂志.2005,11(2)：130-131.
[43]梁启廉,陈小东,李小英,等.复方丹参滴丸加化疗治疗肝癌的临床疗效评价.中医药学刊.2006,24(1)：185-187.
[44]姜德清,立全晰,丁汇清.复方丹参经脐静脉置管门静脉灌注防治肝癌复发的临床研究.实用癌症杂志.2007,22(4):365.
[45]黄智芬,韦劲松,谭志强,等.复方丹参注射液加多巴胺速尿治疗肝癌腹水临床观察.中西医结合肝病杂志.2001,11(1):3-4.
[46]施华平,周玲玲.复方莪术油微球肝动脉栓塞对大鼠移植性肝癌的治疗作用.上海中医药大学学报.23(5):58-60.
[47]邹玺,刘宝瑞,钱晓萍.中医药治疗肿瘤的疗效评价标准的探讨.南京中医药大学学报,2005,21(4):270-271.
[48]Chen SJ. Chen Z. Liang Y,etal.Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia. Proceedings of the National Academy of Sciences of the United States of America.2008; 105(12):4826-31.