疏肝运脾汤治疗肠癌癌因性疲乏患者的临床观察

Clinical Observation on Shugan Yunpi Decoction on Colorectal Cancer Related Fa⁃tigue

目的探讨疏肝运脾汤治疗肠癌癌因性疲乏(Cancer related fatigue,CRF)的临床疗效及作用机制。方法选取2020年3月—2022年3月期间南通市第三人民医院收治的住院或门诊肠癌患者110例作为研究对象,按随机数字表法分为对照组和治疗组,每组各55例。两组患者均给予抗肿瘤治疗如手术、放化疗、介入、分子靶向、免疫等的基础上增加CRF相关干预措施。对照组进行非药物干预,治疗组在对照组基础上加用自拟疏肝运脾汤加减。治疗6个月后,观察比较两组患者临床疗效、不良反应情况,治疗前后中医临床症状等级评分、卡氏评分(Keypunch Performance System,KPS)、Piper疲乏评分、医院焦虑抑郁情绪测量表(Hospital Anxiety and Depression Scale,HAD)评分变化,血清指标[内分泌激素促肾上腺皮质激素(Adrenocorticotropic hormone,ACTH)、皮质醇(Cortisol,CORT)及T细胞亚群]水平。结果治疗后两组患者中医证候积分均较治疗前明显降低,差异有统计学意义(P<0.05);且治疗组明显低于对照组,差异有统计学意义(P<0.05)。治疗后对照组各维度的Piper疲乏评分及总分与治疗前比较,差异无统计学意义(P>0.05);治疗组各维度的Piper疲乏评分及总分均较治疗前明显降低,差异有统计学意义(P<0.05);且治疗组各维度(行为维度、情感维度、感觉维度和认知维度)的Piper疲乏评分及总分均低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者KPS评分较治疗前升高,HAD焦虑、HAD抑郁评分较治疗前降低,差异有统计学意义(P<0.05);且治疗组KPS评分高于对照组,HAD焦虑及HAD抑郁评分低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者血清ACTH、NF-κB p65、TNF-α、sTNF-R1水平较治疗前明显降低,血清CORT水平较治疗前明显升高,差异有统计学意义(P<0.05);且治疗组血清ACTH、NF-κB p65、TNF-α、sTNF-R1水平明显低于对照组,血清CORT水平明显高于对照组,差异有统计学意义(P<0.05)。治疗后两组患者CD8+水平降低,CD3+、CD4+及CD4+/CD8+水平升高,差异有统计学意义(P<0.05);且治疗组CD8+水平低于对照组,CD3+、CD4+及CD4+/CD8+水平均高于对照组,差异有统计学意义(P<0.05)。治疗后治疗组总有效率96.36%(53/55)明显高于对照组80.00%(44/55),差异有统计学意义(P<0.05)。治疗过程中,两组患者均未出现明显不良反应,用药前后的血尿常规、心电图及肝肾功能检查结果均未见异常。结论从基因层面探讨疏肝运脾汤治疗肠癌CRF的分子机制,找到抑制CRF的新靶点———细胞核因子NF-κB的中医组方,改善肿瘤微环境的免疫抑制和炎症状态,提高肠癌临床疗效,提升患者的生活质量,延长其生存时间。

Objective To investigate the clinical effect and mechanism of Shugan Yunpi Decoction in the treat⁃ment of colorectal cancer related fatigue(CRF).Methods A total of 110 inpatients or outpatients with colorectal cancer received by Nantong Third People′s Hospital from March 2020 to March 2022 were selected as the study objects.They were divided into a control group and a treatment group according to random number table method,55 cases in each group.The CRF-related interventions were added in the two groups based on the anti-tumor therapies such as surgery,chemoradio⁃therapy,intervention,molecular targeting,and immunization,etc.Non drug intervention was given in the control group,and the self-designed modified Shugan Yunpi Decoction was applied in the treatment group.After 6 months of treatment,the clinical effect and adverse reactions of the two groups were observed;the changes of Traditional Chinese Medicine(TCM)clinical symptom grade score,Keypunch Performance System(KPS),Piper fatigue score and Hospital Anxiety and Depres⁃sion Scale(HAD)score,the serum indicators[endocrine hormone adrenocorticotropic hormone(ACTH),cortisol(CORT)and T cell subsets]before and after treatment were observed in the two groups.Results After treatment,the TCM syn⁃drome scores in the two groups were significantly lower than those before treatment,and the difference was statistically sig⁃nificant(P<0.05);the TCM syndrome score in the treatment group was significantly lower than that in the control group,and the difference was statistically significant(P<0.05).After treatment,the Piper fatigue scores of all dimensions and the total score in the control group were not significantly changed compared with those before treatment(P>0.05);the Piper fatigue scores of all dimensions and the total score in the treatment group were significantly lower than those before treatment(P<0.05);the Piper fatigue scores of all dimensions(behavioral dimension,emotional dimension,sensory di⁃mension and cognitive dimension)and the total score in the treatment group were significantly lower than those in the con⁃trol group,with statistical significance(P<0.05).After treatment,the KPS scores in the two groups were higher than those before treatment,and the HAD anxiety and HAD depression scores were lower than those before treatment,with statistical significance(P<0.05).The KPS scores in the treatment group were higher than those in the control group,and the HAD anxiety and HAD depression scores in the treatment group were lower than those in the control group,with statistical signif⁃icance(P<0.05).After treatment,the levels of serum ACTH,NF-κB p65,TNF-αand sTNF-R1 in the two groups were significantly lower than those before treatment,and the level of serum CORT was significantly higher than that before treatment,with statistical significance(P<0.05);the levels of serum ACTH,NF-κB p65,TNF-αand sTNF-R1 in the treatment group were significantly lower than those in the control group,and the level of serum CORT was significantly higher than that in the control group,with statistical significance(P<0.05).After treatment,the levels of CD8+in the two groups decreased,and the levels of CD3+,CD4+and CD4+/CD8+increased,with statistical significance(P<0.05).The level of CD8+in the treatment group was lower than that in the control group,and the levels of CD3+,CD4+and CD4+/CD8+in the treatment group were higher than those in the control group,with statistical significance(P<0.05).After treatment,the total effective rate in the treatment group was 96.36%(53/55),which was higher than 80.00%(44/55)in the control group,and the difference was statistically significant(P<0.05).In the course of treatment,no obvious adverse reactions occurred in the two groups,and no abnormal results were found in routine hematuria,electrocardiogram and liver and kidney function test before and after medication.Conclusion To explore the molecular mechanism of Shugan Yunpi Decoction in the treatment of colorectal CRF from the genetic level,and find a new target for CRF inhibition-nuclear fac⁃tor NF-κB,improve the immunosuppression and inflammation of tumor microenvironment,improve the clinical effect of colorectal cancer,improve the quality of life of patients,and prolong their survival time.