Clinical Study on the Treatment of Advanced Liver Cancer of Qi Deficiency and Toxic Stasis Type by Jiawei Yupingfeng San
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摘要:
目的 观察加味玉屏风散治疗气虚毒瘀型晚期肝癌的临床疗效及对患者血清胸腺基质淋巴细胞生成素(TSLP)水平的影响。 方法 采用随机双盲法将120例气虚毒瘀型晚期肝癌患者分为加味玉屏风散组、玉屏风散组和安慰剂组各40例, 3组患者均给予放疗、化疗、介入或靶向治疗等常规治疗,加味玉屏风散组加服加味玉屏风散颗粒, 玉屏风散组加服玉屏风散颗粒, 安慰剂组加服安慰剂, 疗程均为2个月。治疗前后观察3组患者Karnofsky功能状态评分(KPS评分)、中医证候积分、瘤体大小及血清TSLP水平变化情况, 并将肿瘤大小变化与TSLP变化进行相关性分析。 结果 治疗后,玉屏风散组及加味玉屏风散KPS评分均显著提高(P < 0.05,P < 0.01),中医证候总积分显著降低(P < 0.01), 同时明显延缓肿瘤的生长(P < 0.05,P < 0.01),显著降低血清中TSLP水平(P < 0.05,P < 0.01)。此外, 肿瘤大小变化与TSLP变化呈轻度正相关(P < 0.05)。在改善瘤体大小方面, 加味玉屏风散组疗效优于玉屏风散组(P < 0.05)。治疗期间,3组患者均未见明显不良反应。 结论 加味玉屏风散联合常规治疗可显著延缓气虚毒瘀型晚期肝癌患者的肿瘤生长, 改善患者中医症状同时显著提高患者生存质量, 其疗效机制可能为通过降低患者血清TSLP表达, 改善机体免疫状态有关。 Abstract:OBJECTIVE To observe the clinical efficacy and effect on serum thymic stromal lymphopoietin (TSLP) levels of patients with advanced liver cancer of qi deficiency and toxic stasis type by Jiawei Yupingfeng San. METHODS Using random double blind method, 120 patients with advanced liver cancer of qi deficiency and toxic stasis type were randomly divided into 3 groups: Jiawei Yupingfeng San group, Yupingfeng San group, and placebo group, each consisting of 40 cases. All patients in the 3 groups were given conventional treatment such as radiotherapy, chemotherapy, interventional or targeted therapy; Jiawei Yupingfeng San group was given Jiawei Yupingfeng San granules, Yupingfeng San group was given Yupingfeng San granules, and placebo group was given placebo. The course of treatment was 2 months. The changes of Karnofsky functional status score (KPS score), TCM syndrome score, tumor size and serum TSLP level in the 3 groups were observed before and after treatment, and the correlation between the changes of tumor size and TSLP was analyzed. RESULTS After treatment, the KPS scores of Yupingfeng San group and Jiawei Yupingfeng San group were significantly increased (P < 0.05, P < 0.01), TCM syndrome score were decreased (P < 0.01), tumor growth (P < 0.05, P < 0.01) was delayed, and serum TSLP levels (P < 0.05, P < 0.01) were decreased. Furthermore, there was a slight positive correlation between changes in tumor size and changes in TSLP (P < 0.05). In terms of improving tumor size, the curative effect of Jiawei Yupingfeng San group was better than that of Yupingfeng San group (P < 0.05). During the treatment period, no obvious adverse reactions were observed in the 3 groups of patients. CONCLUSION Combined with conventional treatment, Jiawei Yupingfeng San can significantly delay tumor growth in patients with advanced liver cancer of qi deficiency and toxic stasis type and improve patients' TCM syndromes and their quality of survival. The therapeutic mechanism is related to reducing the expression of serum TSLP and improving the immune status of patients, thereby delaying the growth of tumors. -
表 1 3组患者基线资料比较(x±s)
Table 1. Comparison of baseline data of patients in the 3 groups (x±s)
组别 性别 年龄/岁 病程/月 肿瘤大小/cm2 男 女 加味玉屏风散组 19 15 66.8±8.3 6.8±6.2 11.96±12.55 玉屏风散组 22 14 68.1±8.0 6.4±7.2 12.46±11.50 安慰剂组 23 12 65.5±11.1 7.0±6.9 11.97±13.10 表 2 KPS评分细则
Table 2. KPS scoring rules
生活质量 评分 正常, 无症状和体征 100 能进行正常活动, 有轻微症状和体征 90 勉强进行正常活动, 有一些症状或体征 80 生活能自理, 但不能维持正常生活和工作 70 生活能大部分自理, 但偶尔需要别人帮助 60 常需要他人照料 50 生活不能自理, 需要特别照顾和帮助 40 生活严重不能自理 30 病情较重, 需要住院和积极的支持治疗 20 病情危重, 临近死亡 10 死亡 0 表 3 3组患者治疗前后KPS评分变化情况比较(x±s)
Table 3. Comparison of changes in KPS scores of 3 groups of patients before and after treatment(x±s)
组别 例数 治疗前 治疗后 加味玉屏风散组 34 75.88±5.57 82.94±6.29**## 玉屏风散组 36 76.11±5.49 80.28±7.36*## 安慰剂组 35 76.29±4.90 73.71±6.46 注: 与治疗前比较, **P < 0.01;与安慰剂组比较,##P < 0.01。 表 4 3组患者治疗前后KPS评分改善率比较
Table 4. Comparison of improvement rate of KPS scores in 3 groups of patients before and after treatment
组别 例数 提高 稳定 下降 改善率/% 加味玉屏风散组 34 21 10 3 91.18## 玉屏风散组 36 14 14 8 77.78# 安慰剂组 35 5 12 18 48.57 注: 与安慰剂组比较, χ加味玉屏风散组2=14.79, χ玉屏风散组2=6.52, #P < 0.05, ##P < 0.01。 表 5 3组患者治疗前后中医证候积分变化情况比较(x±s)
Table 5. Comparison of TCM syndrome scores between 3 groups of patients before and after treatment (x±s)
组别 时间 胁痛 脘腹胀闷 食少纳呆 少气懒言 加味玉屏风散组 治疗前 0.85±0.56 1.65±0.60 1.71±0.72 1.59±0.66 (n=34) 治疗后 0.56±0.50**## 0.91±0.45**## 0.91±0.57**## 0.91±0.57**## 玉屏风散组 治疗前 0.86±0.64 1.61±0.69 1.69±0.71 1.58±0.73 (n=36) 治疗后 0.78±0.68 1.08±0.50**## 0.97±0.56**## 1.00±0.63**## 安慰剂组 治疗前 0.83±0.57 1.66±0.59 1.69±0.63 1.63±0.73 (n=35) 治疗后 0.89±0.47 1.46±0.51** 1.51±0.56 1.46±0.51 组别 时间 自汗 肌肤甲错 神疲乏力 总积分 加味玉屏风散组 治疗前 1.38±0.70 1.06±0.55 1.76±0.43 9.91±2.25 (n=34) 治疗后 0.82±0.58**## 0.71±0.46** 1.09±0.45**# 5.91±1.86**## 玉屏风散组 治疗前 1.42±0.60 1.00±0.41 1.72±0.66 9.89±2.46 (n=36) 治疗后 1.03±0.56** 0.92±0.50 1.00±0.63**# 6.78±1.88**## 安慰剂组 治疗前 1.37±0.65 0.97±0.45 1.74±0.78 9.89±1.92 (n=35) 治疗后 1.26±0.61 0.91±0.51 1.37±0.65** 8.86±1.54** 注: 与治疗前比较,**P < 0.01;与安慰剂组比较,#P < 0.05,##P < 0.01。 表 6 3组患者治疗前后肿瘤大小比较(x±s, cm2)
Table 6. Comparison of tumor size before and after treatment in 3 groups of patients (x±s, cm2)
组别 时间 肿瘤大小 加味玉屏风散组 治疗前 11.96±12.55 (n=34) 治疗后 9.90±11.94*# 玉屏风散组 治疗前 12.46±11.50 (n=36) 治疗后 12.28±12.36 安慰剂组 治疗前 11.97±13.10 (n=35) 治疗后 16.14±15.87** 注: 与治疗前比较, *P < 0.05,**P < 0.01;与安慰剂组比较, #P < 0.05。 表 7 3组患者治疗前后肿瘤大小变化比较
Table 7. Comparison of changes in tumor size between 3 groups of patients before and after treatment
组别 例数 CR PR SD PD 缓解率/% 控制率/% 加味玉屏风散组 34 0 5 22 7 14.71 79.41##△ 玉屏风散组 36 0 2 18 16 5.56 55.56# 安慰剂组 35 0 0 11 24 0 31.43 注: 与安慰剂组比较,#P < 0.05, ##P < 0.01;与玉屏风散组比较, △P < 0.05。 表 8 3组患者治疗前后血清TSLP水平比较(x±s, pg·mL-1)
Table 8. Comparison of serum TSLP before and after treatment in 3 groups of patients (x±s, pg·mL-1)
组别 时间 TSLP 加味玉屏风散组 治疗前 8.51±3.55 (n=34) 治疗后 7.25±4.12*# 玉屏风散组 治疗前 8.70±5.31 (n=36) 治疗后 7.42±4.16*# 安慰剂组 治疗前 8.43±4.45 (n=35) 治疗后 9.52±4.98 注: 与治疗前比较, *P < 0.05;与安慰剂组比较, #P < 0.05。 表 9 肿瘤大小变化与血清TSLP变化趋势相关性分析(n=105)
Table 9. Correlation analysis between tumor size changes and serum TSLP change trends (n=105)
项目 缓解 稳定 进展 肿瘤变化 7 51 47 TSLP变化 19 68 18 注: r=0.320,P < 0.01。 -
[1] VOGEL A, MEYER T, SAPISOCHIN G, et al. Hepatocellular carcinoma[J]. Lancet, 2022, 400(10360): 1345-1362. doi: 10.1016/S0140-6736(22)01200-4 [2] ZHOU M G, WANG H D, ZENG X Y, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017[J]. Lancet, 2019, 394(10204): 1145-1158. doi: 10.1016/S0140-6736(19)30427-1 [3] 陈楚钦, 施练迅, 汤子明, 等. 索拉菲尼对不同肝功能 Child-Pugh 分级晚期肝癌患者的疗效和安全性比较[J]. 广东医学, 2017, 38(18): 2865-2867. doi: 10.3969/j.issn.1001-9448.2017.18.035CHEN C Q, SHI L X, TANG Z M, et al. Comparison of efficacy and safety of sorafenib in patients with advanced liver cancer with different Child-Pugh grades of liver function[J]. Guangdong Med J, 2017, 38(18): 2865-2867. doi: 10.3969/j.issn.1001-9448.2017.18.035 [4] HE W, LIAO L E, HU D D, et al. Apatinib versus sorafenib in patients with advanced hepatocellular carcinoma: A preliminary study[J]. Ann Transl Med, 2020, 8(16): 1000. doi: 10.21037/atm-20-5298 [5] LIU X L, LI M G, WANG X H, et al. Effects of adjuvant traditional Chinese medicine therapy on long-term survival in patients with hepatocellular carcinoma[J]. Phytomedicine, 2019, 62: 152930. [6] 刘展华, 庄振杰, 黄慈辉, 等. 肝癌炎性微环境与中医药干预疗法概述[J]. 广州中医药大学学报, 2018, 35(5): 937-942. https://www.cnki.com.cn/Article/CJFDTOTAL-REST201805038.htmLIU Z H, ZHUANG Z J, HUANG C H, et al. Overview of inflammatory micro-environment of hepatocellular carcinoma and related Chinese medicine intervention therapies[J]. J Guangzhou Univ Tradit Chin Med, 2018, 35(5): 937-942. https://www.cnki.com.cn/Article/CJFDTOTAL-REST201805038.htm [7] VARRICCHI G, PECORARO A, MARONE G, et al. Thymic stromal lymphopoietin isoforms, inflammatory disorders, and cancer[J]. Front Immunol, 2018, 9: 1595. doi: 10.3389/fimmu.2018.01595 [8] 曹志新, 陈孝平, 吴在德. 肝癌合并肝硬化患者脾脏Th1/Th2细胞因子免疫状态的研究[J]. 中华实验外科杂志, 2001, 18(6): 518-519. doi: 10.3760/j.issn:1001-9030.2001.06.016CAO Z X, CHEN X P, WU Z D. A study on the spleen Th1/Th2 cytokines immunological condition in the patients with primary hepatocellular carcinoma combined with liver cirrhosis[J]. Chin J Exp Surg, 2001, 18(6): 518-519. doi: 10.3760/j.issn:1001-9030.2001.06.016 [9] 程海波, 吴勉华. 周仲瑛教授"癌毒" 学术思想探析[J]. 中华中医药杂志, 2010, 25(6): 866-869. https://www.cnki.com.cn/Article/CJFDTOTAL-BXYY201006022.htmCHENG H B, WU M H. Discussion on academic thought of Professor ZHOU Zhong-ying about cancerous toxin[J]. China J Tradit Chin Med Pharm, 2010, 25(6): 866-869. https://www.cnki.com.cn/Article/CJFDTOTAL-BXYY201006022.htm [10] 赵素霞, 刘会丽, 樊峥, 等. 玉屏风散辅助治疗原发性肝癌的疗效及对抗肿瘤免疫的影响[J]. 肿瘤药学, 2017, 7(6): 713-717. doi: 10.3969/j.issn.2095-1264.2017.06.15ZHAO S X, LIU H L, FAN Z, et al. Influence of Yupingfeng Powder adjuvant therapy on treatment effect and anti-tumor immunity of patients with primary liver cancer[J]. Anti Tumor Pharm, 2017, 7(6): 713-717. doi: 10.3969/j.issn.2095-1264.2017.06.15 [11] 袁琴, 姚霏, 张露蓉. 玉屏风散通过胸腺基质淋巴细胞生成素改变Th1/Th2的平衡发挥抗肝癌效应的研究[J]. 南通大学学报(医学版), 2016, 36(6): 509-513. https://www.cnki.com.cn/Article/CJFDTOTAL-NTYX201606001.htmYUAN Q, YAO F, ZHANG L R. Research on inhibition effects of Yupingfeng Powder through TSLP change the balance of Th1/Th2 in hepatocellular carcinoma[J]. J Nantong Univ Med Sci, 2016, 36(6): 509-513. https://www.cnki.com.cn/Article/CJFDTOTAL-NTYX201606001.htm [12] 刘敏, 王明武. 解毒破瘀法抑制三阴性乳腺癌复发与转移的临床研究[J]. 南京中医药大学学报, 2016, 32(2): 111-113. http://xb.njucm.edu.cn/article/id/zr20160204LIU M, WANG M W. Clinical research on the inhibition of recurrence and metastasis of triple negative breast cancer with the method of detoxification and blood stasis dissipating[J]. J Nanjing Univ Tradit Chin Med, 2016, 32(2): 111-113. http://xb.njucm.edu.cn/article/id/zr20160204 [13] 张琳, 高勇. 复方红豆杉胶囊对Walker-256移植性肝癌大鼠HIF-1α、VEGF及PCNA表达的影响[J]. 陕西中医, 2019, 40(2): 148-151, 155. doi: 10.3969/j.issn.1000-7369.2019.02.003ZHANG L, GAO Y. The effects of Fufang Hongdoushan capsule in the expression of HIF-1α, VEGF and PCNA in Walker-256 transplanted liver cancer rats[J]. Shaanxi J Tradit Chin Med, 2019, 40(2): 148-151, 155. doi: 10.3969/j.issn.1000-7369.2019.02.003 [14] 刘同祥, 张艳平, 徐羽, 等. 紫杉醇联合三尖杉宁碱诱导人肝癌HepG2细胞凋亡[J]. 中国实验方剂学杂志, 2010, 16(9): 115-118, 122. doi: 10.3969/j.issn.1005-9903.2010.09.035LIU T X, ZHANG Y P, XU Y, et al. Effect of taxol combining with cephalomannine on apoptosis of liver cancer cell HepG2[J]. Chin J Exp Tradit Med Formulae, 2010, 16(9): 115-118, 122. doi: 10.3969/j.issn.1005-9903.2010.09.035 [15] 王海永, 张晨月, 李佳, 等. 蟾毒灵抑制肝癌干细胞lncRNAs分子筛选研究[J]. 中国中医药信息杂志, 2021, 28(12): 41-44. https://www.cnki.com.cn/Article/CJFDTOTAL-XXYY202112008.htmWANG H Y, ZHANG C Y, LI J, et al. Study on screening of lncRNAs involved in the inhibitory effect of bufalin on hepatocellular carcinoma stem cells[J]. Chin J Inf Tradit Chin Med, 2021, 28(12): 41-44. https://www.cnki.com.cn/Article/CJFDTOTAL-XXYY202112008.htm [16] 袁贤达, 王骏, 金明吉, 等. 华蟾素油剂对肝癌细胞的体内外抑制活性及肿瘤微环境中对免疫细胞的影响[J]. 世界中西医结合杂志, 2019, 14(12): 1629-1637. https://www.cnki.com.cn/Article/CJFDTOTAL-SJZX201912002.htmYUAN X D, WANG J, JIN M J, et al. Inhibitory activity of Huachansu corn oil solvent on liver cancer cells in vitro and in vivo and effects on immune cells in tumor microenvironment[J]. World J Integr Tradit West Med, 2019, 14(12): 1629-1637. https://www.cnki.com.cn/Article/CJFDTOTAL-SJZX201912002.htm [17] 周星言, 戴国瑶. 雷公藤甲素通过调节沉默信息调节因子1/p53途径抑制肝癌HepG2细胞的增殖和迁移[J]. 胃肠病学和肝病学杂志, 2022, 31(10): 1178-1182. doi: 10.3969/j.issn.1006-5709.2022.10.020ZHOU X Y, DAI G Y. Triptolide inhibits proliferation and migration of liver cancer HepG2 cells by regulating the silent information regulator 1/p53 pathway[J]. Chin J Gastroenterol Hepatol, 2022, 31(10): 1178-1182. doi: 10.3969/j.issn.1006-5709.2022.10.020 [18] 顾军花, 刘嘉湘. 刘嘉湘教授"扶正治癌" 理论核心及运用方法[J]. 中国中西医结合杂志, 2017, 37(4): 495-499. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZXJ201704028.htmGU J H, LIU J X. Core of professor Liu Jiaxiang's theory of "strengthening the body resistance and treating cancer" and its application method[J]. Chin J Integr Tradit West Med, 2017, 37(4): 495-499. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZXJ201704028.htm [19] 《原发性肝癌诊疗规范(2017年版)》编写专家委员会. 原发性肝癌诊疗规范(2017年版)[J]. 消化肿瘤杂志(电子版), 2017, 9(4): 213-228. https://www.cnki.com.cn/Article/CJFDTOTAL-ZPWZ201907004.htmExpert Committee for the Compilation of Diagnosis and Treatment Standards for Primary Liver Cancer (2017 Edition). Diagnosis and treatment standards for primary liver cancer (2017 edition)[J]. J Dig Oncol Electron Version, 2017, 9(4): 213-228. https://www.cnki.com.cn/Article/CJFDTOTAL-ZPWZ201907004.htm [20] 中药新药临床研究指导原则: 试行[M]. 北京: 中国医药科技出版社, 2002.Guiding principles for clinical research of new Chinese medicine: Trial implementation[M]. Beijing: China Medical Science and Technology Press, 2002. [21] 中国癌症基金会. 基层医生肿瘤诊治手册[M]. 北京: 北京大学医学出版社, 2008.China Cancer Foundation. Handbook for cancer diagnosis and treatment for primary doctors[M]. Beijing: Peking University Medical Press, 2008. [22] EISENHAUER E A, THERASSE P, BOGAERTS J, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)[J]. Eur J Cancer, 2009, 45(2): 228-247. doi: 10.1016/j.ejca.2008.10.026 [23] PROTTI M P, DE MONTE L. Thymic stromal lymphopoietin and cancer: Th2-dependent and-independent mechanisms[J]. Front Immunol, 2020, 11: 2088. doi: 10.3389/fimmu.2020.02088
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