健脾补肾序贯方减轻结肠癌辅助化疗所致骨髓抑制疗效观察及机制探讨

目的 探究健脾补肾序贯方对结肠癌患者辅助化疗所致骨髓抑制的改善作用及其可能机制。方法 将北京大学肿瘤医院收治的120例结肠癌患者随机分为试验组(n=61)和对照组(n=59),试验组采用CapeOX化疗方案联合健脾补肾序贯方治疗,对照组使用CapeOX化学方案联合健脾补肾序贯方安慰剂治疗。比较2组患者骨髓抑制发生情况、血细胞计数变化情况及治疗前后血清IL-3、SCF、GM-CSF水平。结果 试验组白细胞减少发生率35.09%、中性粒细胞减少发生率36.84%,低于对照组(53.85%、57.69%),差异有统计学意义(P<0.05)。试验组血小板下降发生率50.88%、贫血发生率26.32%,低于对照组(57.69%、34.62%),差异无统计学意义(P>0.05)。治疗后,2组各治疗时点白细胞、中性粒细胞、血小板计数比较,差异均无统计学意义(P>0.05)。治疗后,试验组血清IL-3、SCF和GM-CSF水平均上升,对照组IL-3和GM-CSF水平下降,SCF水平稍上升。治疗后试验组SCF水平高于对照组,差异有统计学意义(P<0.05)。结论 健脾补肾序贯方可减轻结肠癌化疗所引起的白细胞及中性粒细胞减少,其机制可能与促进造血生长因子分泌,从而改善骨髓抑制有关。

祛邪胶囊对晚期结直肠癌患者血清代谢组学及肠道菌群分布影响的随机对照研究

目的观察中药复方祛邪胶囊对晚期结直肠癌患者血清代谢组学及肠道菌群多样性分布的影响。方法采用临床随机双盲安慰剂对照研究方法,对入组患者给予祛邪胶囊或安慰剂干预1个月,收集患者治疗前后外周血及粪便样本,通过液质联用(LC-MS)非靶向代谢组学分析以及16SrRNA肠道菌群多样性分析方法进行检验,并通过生物分析云平台进行组间差异性比较以及关联分析。结果研究共入组40例晚期结直肠癌患者,最终34例患者完成访视并纳入分析,结果显示祛邪胶囊组治疗后天竺葵色素-3-槐糖苷、3-羟基-2-萘甲酸、色氨酸-甜菜碱均显著高于治疗前,而烟酰胺下降,安慰剂组干预后烟酰胺上升,与患者肠道菌群多样性进行联合分析,祛邪胶囊组血清天竺葵色素-3-槐糖苷丰度与患者肠道菌群中副沙门氏菌、黏胶球形菌分布正相关,与链球菌分布负相关。结论祛邪胶囊可能通过调节晚期结直肠癌患者烟酸和烟酰胺代谢、花青素代谢以及色氨酸代谢发挥抗癌作用,可能与提高肠道有益菌、降低有害菌分布比例有关。

基于单中心回顾性真实世界研究的晚期结直肠癌三线中西医结合治疗现状及疗效分析

目的探讨中西医结合方案在晚期结直肠癌三线治疗中的实际临床应用情况与疗效分析。方法本研究采用基于单中心真实世界数据的回顾性分析研究方法,筛选自2018年7月至2021年7月在中国中医科学院西苑医院住院接受中西医结合治疗的全部经历过晚期一线、二线、三线治疗过程的结直肠癌患者。通过住院病历系统中的医疗记录采集患者相关疾病信息、治疗用药方案、各线治疗开始和失败时间、中医证型等资料,并采用描述性统计学方法进行分析。采用Kaplan Meier分析不同疾病信息及治疗方案患者的三线无进展生存时间(Progression Free Survival,PFS),在此基础上采用多因素Cox回归分析判断影响因素。结果研究共筛选纳入55例晚期结直肠癌患者,中西医结合三线治疗中位PFS为(5.0±0.6)月,常用三线西医治疗方案为含呋喹替尼、瑞格非尼、阿帕替尼靶向治疗的方案(应用频率合计33%)、含伊立替康双药或单药联合靶向治疗(31%);左半结肠癌、基因检测全野生型、微卫星稳定的患者具有相对更长的三线PFS,但差异无统计学意义。所纳入病例中常见中医证型为脾肾亏虚型(61.8%)和肝郁脾虚型(18.2%),多因素Cox回归分析显示肝郁脾虚证型是三线PFS时间的独立危险因素(风险比2.57,P=0.044)。结论中西医结合三线治疗晚期结直肠癌可能有助于患者生存获益,且与基因检测状态、中医证型等因素相关。

基于中医脾虚量表的结直肠癌患者临床特征、肠道菌群及免疫功能相关性研究

目的:基于中医脾虚量表分析结直肠癌脾气虚与非脾气虚患者在临床特征、肠道菌群及TB淋巴细胞亚群的差异性及相关性。方法:采用前瞻性临床观察研究方法对2018年3月至2020年12月期间在中国中医科学院西苑医院、北京大学肿瘤医院门诊及病房就诊的96例结直肠癌患者进行临床信息、肠道菌群及TB淋巴细胞亚群的相关分析。结果:脾气虚组与非脾气虚组在自然杀伤性T细胞绝对值的比较中差异有统计学意义(45.5,IQR 50.8 vs.28 IQR 52,U=208,P=0.049);肠道菌群物种组成差异分析结果显示,非脾气虚组中双歧杆菌属丰度显著低于脾气虚组且差异有统计学意义(P<0.05)。结论:结直肠癌脾气虚与非脾气虚患者在肠道菌群组成及TB淋巴细胞亚群分布方面存在差异,可为探索结直肠癌脾气虚证的生物学特征提供客观依据。

基于网络药理学探讨六君安胃方减少结肠癌化疗期间消化道不良反应的作用机制研究

目的通过网络药理学方法探讨六君安胃方减少结肠癌化疗期间消化道不良反应的作用机制。方法通过检索中药系统药理学分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)对六君安胃方中六味中药的化学成分、作用靶点进行筛选,并在GeneCards、在线人类孟德尔遗传数据库(Online Mendelian Inheritance in Man,OMIM)等相关数据库中筛选出"chemotherapy-induced nausea and vomiting(CINV)"、"chemotherapy-induced diarrhea(CID)"相关靶点。利用STRING和Cytoscape3.6.0构建PPI网络图并通过网络拓扑分析获得关键蛋白靶点;利用R软件ClusterProfiler进行GO及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路功能富集分析;利用AutoTools1.5.6进行有效化学成分与关键蛋白靶点的分子对接。结果六君安胃方中的中药有效化学成分共103个,潜在作用靶点406个,CINV、CID疾病相关作用靶点851个,通过PPI网络拓扑分析得到关键蛋白靶点,前5个分别为AKT1、MAPK3、MAPK1、MAPK8、JUN;GO富集结果显示,氧化应激反应、凋亡信号通路调节、膜筏、膜微区域、泛素样蛋白连接酶结合、蛋白质丝氨酸/苏氨酸激活酶活性等排名靠前;KEGG富集通路结果显示,PI3K-AKt信号通路、MAPK信号通路、TNF信号通路等信号通路为主要作用通路;分子对接显示党参中的木犀草素与AKT1结合性最好。结论六君安胃方可能通过调节AKT1、MAPK3、MAPK1等关键蛋白,干预PI3K-AKt等相关炎症信号通路来减少化疗期间消化道不良反应。

Chinese Medicine Combined with Adjuvant Chemotherapy for Improving Myelosuppression in Colorectal Cancer Patients:A Systematic Review and Network Meta-Analysis

Objective To assess the effectiveness of Chinese herbal medicine(CHM)combined with adjuvant chemotherapy on myelosuppression for colorectal cancer(CRC)patients using network meta-analysis(NMA).Methods Literature searches in both international(PubMed,Embase,Web of Science,and Cochrane Library)and Chinese(China Science and Technology Journal Database,Wanfang Data,China National Knowledge Infrastructure)databases for relevant randomized controlled trials(RCTs)were conducted from inception until October 10,2022.We included RCTs of patients who received CHM combined with chemotherapy,including FOLFOX,XELOX,FOLFIRI,and other relevant regimens in the CHM treatment group.The outcomes included the incidence of myelosuppression,leukopenia,hemoglobin reduction,and thrombocytopenia.Two reviewers independently screened the databases,extracted the data,and assessed the risk of bias and credibility of evidence.RevMan 5.4.1 software and STATA 14.0 were used to perform the NMA.Results A total of 31 RCTs were included,published from 2008 to 2021 in Chinese.Among these,2,314 participants comparing the following 9 CHMs were identified:Shengbai Recipe(SBR),Bazhen Decoction(BZD),Jianpi Jiedu Recipe(JJR),Jianpi Recipe(JR),Compound Cantharis Capsule(CCC),Zaofan Pill(ZFP),Guilu Erxian Gel(GL),Buzhong Tiaogan Decoction(BZ),and Qiamagu Capsule(QM).The results of NMA found an indirect comparison.Based on the surface under the cumulative ranking curve(SUCRA),the ZFP+chemotherapy group had the lowest incidence of myelosuppression,with an odds ratio(OR)of 0.08[95%confidence interval(CI):0.01,0.76],whereas the GL+chemotherapy group had the lowest incidence of leukopenia,hemoglobin reduction,and thrombocytopenia,with an OR of 5.25(95%CI:2.41,11.43),4.66(95%CI:2.23,9.72),and 0.27(95%CI:0.13,0.54),respectively.Moreover,BZD+chemotherapy could alleviate leukopenia,hemoglobin reduction,and thrombocytopenia(P<0.01).Pairwise comparison showed that there was no difference in the efficacy among the 8 CHMs+chemotherapy group.The comparison and adjustment funnel plot indicated that small-study effect had no impact on these outcomes.Conclusions This NMA provided evidence to support that patients with CRC benefit from receiving different combination of CHM chemotherapies.Among these,GL plus chemotherapy and BZD plus chemotherapy were the more effective for myelosuppression in patients;however,as the qualtiy of evidence is insufficient,further research is needed.(PROSPERO, No. CRD42022369025.

结肠癌辅助化疗期中医症状量表信度效度检验与临床实践应用分析

目的评价《中医症状量表》的信度效度,观察健脾补肾序贯方对结肠癌辅助化疗期患者中医症状严重程度的改善情况。方法纳入中国中医科学院西苑医院111例结肠癌根治术后患者用于量表的信度、效度评价,计算量表的克朗巴赫α系数(Cronbach’sα)以评估量表一致性,应用因子分析评价量表的结构效度。本研究是一项随机、对照、双盲安慰剂、多中心临床研究的二次分析,在2018年12月—2021年12月期间,对纳入的400例结肠癌根治术后的患者进行1:1的随机分配为试验组和安慰剂组。试验组口服健脾补肾序贯方,安慰剂组口服健脾补肾序贯方模拟剂,在接受XELOX方案辅助化疗期间加载服用。二次分析主要比较两组患者中医症状改善情况、中医症状随时间变化情况,评价健脾补肾序贯方对症状改善的疗效。结果结肠癌辅助化疗期《中医症状量表》共包括11个症状条目。量表Cronbach’sα系数为0.698,重测信度为0.730,共筛选出4个公因子,总方差累计贡献率60.753%,因子载荷均大于最小可接受值。临床研究部分统计结果分析显示,试验组与安慰剂组在呕吐评分中差异有统计学意义(Z=2.069,P=0.039)。重复测量结果显示,在服用健脾补肾序贯方后呕吐(P=0.003)、麻木(P<0.001)、腹泻(P=0.023)、便秘(P=0.007)、怕冷(P=0.024)、夜尿(P=0.001)、自汗(P=0.017)、口腔溃疡(P=0.002)差异有统计学意义。结论《中医症状量表》具有良好的信度、效度,可应用于临床评价结肠癌辅助化疗期间中医症状的改善情况。健脾补肾序贯方能够有效改善结肠癌患者辅助化疗期间呕吐严重程度。

Effect of Jianpi Bushen Sequential Formula on Adjuvant Chemotherapy of Colon Cancer:Study Protocol for a Randomized Controlled Trial

Background The side effects of chemotherapy-induced nausea and vomiting(CINV)and myelosuppression reduce the cancer patients’adherence to chemotherapy.Many Chinese patients choose Chinese medicine(CM)during chemotherapy to reduce side effects;however,the evidence is lacking.The efficacy of a CM herbal treatment protocol,Jianpi Bushen Sequential Formula(健脾补肾续贯方,JBSF)will be evaluated on chemotherapy completion rate among patients with colon cancer.Methods A multi-center double-blind randomized controlled trial(RCT)will be conducted on 400 patients with colon cancer who will receive 8 cycles of adjuvant chemotherapy with oxaliplatin and capecitabine(CAPEOX).Patients will be randomized 1:1 to receive the JBSF or placebo formula.The primary outcome is the overall chemotherapy completion rate.The secondary outcomes include individual chemotherapy completion rate,4-cycle completion rate of chemotherapy,time to treatment failure,relative dose intensity and treatment toxicity.Follow-up visits will be scheduled before every and after last chemotherapy.Discussion This study will provide evidence on whether JBSF can improve the chemotherapy completion rate and reduce side effects among patients with colon cancer.(Trial registration:Clinical Trials.gov,No.NCT03716518)。