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 
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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
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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。
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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。
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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。
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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。
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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。
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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。
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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。
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