目的:系统评价植物性药物治疗胃癌(GC)所致癌因性疲乏(CRF)的疗效和安全性,并采用网络分析确定其潜在的药理机制。方法:中国国家知识基础设施(CNKI)等数据库,SinoMed,万方,Pubmed,Embase,科克伦图书馆,和WebofScience从开始至2022年4月18日的随机对照试验(RCT)进行了检索.方法学质量评估使用协作工具Cochrane,采用RevMan5.4和STATA16软件进行数据分析。选择纳入研究中使用频率最高的植物性药物。化学成分,行动目标,疾病目标,并基于网络分析筛选了这些植物性药物的共享靶点,以探索胃癌(GC)患者治疗CRF的潜在机制。结果:共有13项研究纳入986例胃CRF患者,符合纳入标准。结果表明,植物药能提高胃CRF的CRF评分,包括CRF二分数据的总分[赔率比(OR)=4.22;95%置信区间(CI)1.67-10.68;p=0.002],CRF连续数据的总分[标准化平均差(SMD)=-0.98;95%CI-1.36至-0.60;p<0.00001],Piper疲劳量表(PFS)评分的情感分量表[加权平均差(MD)=-0.79;95CI-0.92至-0.65;p<0.00001],PFS评分的感觉分量表(MD=-0.57;95CI-0.77至-0.37;p<0.00001),PFS得分的行为分量表(MD=-1.05;95%CI-1.29至-0.82;p<0.00001),生活质量问卷核心30(QLQ-C30)(MD=10.53,95%CI8.26至12.80;p<0.00001),和Karnofsky绩效状态量表(KPS)(MD=5.18,95%CI2.60至7.76;p<0.0001)。植物药组的不良反应较对照组轻。从在线数据库共获得44种化学成分和241种潜在靶标,121种药物靶标与GC患者的CRF疾病靶标重叠。此外,五种关键活性成分,也就是槲皮素,豆甾醇,木犀草素,山奈酚,和异鼠李素,以及五个关键靶标,包括AKT1,TP53,TNF,VEGFA,和CASS3进行了筛选。此外,五个关键的信号通路,包括癌症,乙型肝炎,前列腺癌,丙型肝炎,和胰腺癌通路,通过富集分析获得。结论:研究结果表明,植物药对GC患者的CRF具有积极作用。然而,更精心设计,多中心,需要大样本随机对照试验来评估植物药对GC患者CRF的有效性。
Objective: To systematically review the efficacy and safety of botanical drugs in the treatment of cancer-related fatigue (CRF) caused by gastric cancer (GC) and to determine the underlying pharmacological mechanisms using a network analysis. Methods: Databases such as
China National Knowledge Infrastructure (CNKI), SinoMed, Wanfang, Pubmed, Embase, Cochrane Library, and Web of Science were searched for randomized controlled trials (RCTs) from inception to 18 April 2022. Methodological quality assessment was performed using the collaborative tool Cochrane, and data analysis were carried out using RevMan 5.4 and STATA 16 software. The botanical drugs with the highest frequency of use in the included studies was selected. The chemical composition, targets of action, disease targets, and shared targets of these botanical drugs were screened based on network analysis to explore the potential mechanisms of treating CRF in patients with gastric cancer (GC). Results: A total of 13 studies that included 986 patients with gastric CRF met the inclusion criteria. The results showed that botanical drugs could improve the CRF scores of gastric CRF, including the total scores of CRF dichotomous data [Odds Ratio (OR) = 4.22; 95% confidence interval (CI) 1.67-10.68; p = 0.002], the total scores of CRF continuous data [Standardized Mean Difference (SMD) = -0.98; 95% CI -1.36 to -0.60; p < 0.00001], the affective subscales of Piper Fatigue Scale (PFS) scores [Weighted Mean Difference (MD) = -0.79; 95%CI -0.92 to -0.65; p < 0.00001], the sensory subscales of PFS scores (MD = -0.57; 95%CI -0.77 to -0.37; p < 0.00001), the behavioral subscales of PFS scores (MD = -1.05; 95% CI -1.29 to -0.82; p < 0.00001), Quality of Life Questionnaire Core 30 (QLQ-C30) (MD = 10.53, 95% CI 8.26 to12.80; p < 0.00001), and the Karnofsky Performance Status scale (KPS) (MD = 5.18, 95% CI 2.60 to 7.76; p < 0.0001). The botanical drugs group had milder adverse effects than the control group. A total of 44 chemical components and 241 potential targets were obtained from the online database and 121 drug targets overlapped with the disease targets of CRF in patients with GC. Moreover, five key active ingredients, namely quercetin, Stigmasterol, luteolin, kaempferol, and isorhamnetin, as well as five key targets including AKT1, TP53, TNF, VEGFA, and CASP3, were screened. In addition, five key signaling pathways, including cancer, Hepatitis B, Prostate cancer, Hepatitis C, and Pancreatic cancer pathways, were obtained through enrichment analysis. Conclusion: The results of the study showed that botanical drugs have positive effects on CRF in patients with GC. However, more well-designed, multicenter, and large sample-sized Randomized Controlled Trials are required to evaluate the effectiveness of botanical drugs on CRF in patients with GC.