Colorectal cancer (CRC), as a high-incidence malignancy, continues to present significant challenges in prevention, screening, and treatment. Curcumin (Cur) exhibits notable anti-inflammatory and anticancer properties. Despite its poor solubility in water and low bioavailability, high concentrations of Cur are detected in the gastrointestinal tract after oral administration, suggesting that it may directly interact with the gut microbiota and exert regulatory effects. This study aims to explore the mechanisms by which Cur improves CRC by modulating gut microbiota. Firstly, we evaluated the effect of Cur on CRC cell viability in vitro using the MTT assay, and the results showed a significant inhibitory effect on CRC cell growth. The IC50 values for Cur in CT26 and RKO cells were 23.52 μM, 16.11 μM, and 13.62 μM at 24, 48, and 72 hours, respectively, and 26.3 μM, 16.52 μM, and 14.22 μM at 24, 48, and 72 hours, respectively. Cur induced apoptosis and caused G2 phase cell cycle arrest in tumor cells. Subsequently, we established a CRC mouse model. Oral administration of Cur at 15 mg kg-1 and 30 mg kg-1 inhibited CRC progression, as evidenced by reduced tumor volume, histological analysis, immunohistochemistry, and an increased number of CD8+ T cells infiltrating the tumors. Ferroptosis in tumor cells was also observed. Cur partially restored the gut microbiota of CRC mice, altering the abundance and diversity of the gut microbiota and affecting serum metabolite distribution, with significant increases in the abundance of SCFA-producing microbes such as Lactobacillus and Kineothrix. To verify causality, we designed a fecal microbiota transplantation (FMT) experiment. Compared with CRC mice, the fecal microbiota from Cur-treated mice significantly alleviated CRC symptoms, including slowed tumor growth, enhanced CD8+ T cell tumor infiltration, and induced ferroptosis in tumor cells. Additionally, when gut microbiota was depleted with antibiotics, Cur's antitumor effects disappeared, suggesting that Cur mitigates CRC in a gut microbiota-dependent manner. These findings provide new insights into the mechanisms underlying CRC and propose novel therapeutic interventions, emphasizing the interaction between gut microbiota and immune responses within the tumor immune microenvironment (TIME).

目的:从肠道菌群探讨化铁丸抗结肠癌的效果及作用机制,为临床应用化铁丸提供理论依据.方法:体外培养结肠癌HCT116 细胞,采用皮下接种的方法构建裸小鼠HCT116 细胞移植瘤模型,选取造模成功的 32 只SPF级雄性BALB/c裸小鼠,分为对照组和化铁丸低、中、高剂量组,每组 8 只.化铁丸低、中、高剂量组分别予 1.82 g/(kg·d)、3.64 g/(kg·d)、14.56 g/(kg·d)化铁丸药液灌胃,对照组予等体积生理盐水灌胃,连续21 d,观察各组裸小鼠一般情况及移植瘤体积变化,通过 16SrDNA基因测序检测各组裸小鼠粪便菌群的差异.结果:实验期间,化铁丸各剂量组裸小鼠精神状况良好,遇刺激反应灵敏,饮食饮水量与对照组无明显差异.对照组裸小鼠体质量变化幅度小,化铁丸低、中、高剂量组裸小鼠体质量升幅高于对照组,但差异均无统计学意义(P＞0.05).随时间推移各组瘤体积呈增长趋势,自第 13 天起,化铁丸各剂量组与对照组比较,移植瘤体积生长较慢,差异有统计学意义(P＜0.05,P＜0.01);第 21 天时,化铁丸中剂量组肿瘤体积最小,对照组肿瘤体积最大,差异有统计学意义(P＜0.01).化铁丸中剂量组抑瘤率最高,为 44.0%,化铁丸低剂量组和高剂量组抑瘤率分别为 36.0%、32.1%.化铁丸中剂量组裸小鼠肠道菌群丰度及多样性提高,梭菌目Clostridiales、梭菌纲Clostridia、毛螺菌科Lachnospiraceae_FCS020_group、瘤胃球菌属Ruminococcaceae_NK4A214_group、Ruminiclostridium_5、Lachnoclostridium、Parasutterella的丰度增加,条件致病菌属Enterobacter丰度降低.结论:化铁丸能够抑制结肠癌发展,且中剂量效果最好;其机制可能为提高裸小鼠肠道菌群丰度及多样性,增加Clostridiales丰度,降低条件致病菌Enterobacter的丰度,抑制结肠癌瘤体生长.

肠道微生态与结直肠癌(CRC)发生发展的关系目前已成为研究的热点.肠道微生态的改变参与了结直肠黏膜缓慢发展成腺瘤和息肉,最终演变成CRC的整个过程,CRC患者存在肠道微生态紊乱的现象,CRC是宿主肠道免疫稳态失衡和表观遗传变异的积累.现全面回顾性分析最近的相关研究,探讨肠道微生态对肠道免疫稳态和表观遗传修饰的影响及与CRC发生发展的关系,重点从肠道微生物和肠道微生物源代谢调节物2个方面进行总结,以更有效地对CRC进行预防、诊断、治疗和管理.

阐述中医在防控新型冠状病毒肺炎(Corona Virus Disease 2019,COVID-19)(简称新冠肺炎)的必要性和优势,并就普通民众运用中医预防疫情给出建议,旨在更好地发挥中医防控新冠肺炎的作用.

恶性肿瘤是临床常见病和多发病,患者经手术、化疗、放疗后,易损伤人体阳气,治疗常用温阳扶正之法.附子为温阳扶正要药,该文结合临床病案探讨附子在恶性肿瘤中的应用.

"正气为本、顺势疗疾"是中医防治各类疾病最重要的特色和优势,面对新型冠状病毒肺炎如此严峻的疫情,我们要努力发挥中医"正气为本、顺势疗疾"的特色和优势.本文首先论述了中医"正气为本、顺势疗疾"思想溯源及核心内涵和新型冠状病毒肺炎的临床特点,探讨如何将中医扶正祛邪经典方剂人参败毒散和小柴胡加石膏汤应用于该传染病中,以期更好发挥中医特色和优势,中西医携手更好抗击新型冠状病毒肺炎,降低该病的发病率和病死率.

新型冠状病毒肺炎(corona virus disease 2019,COVID-19,简称新冠肺炎)病因为感受“戾气”,发热贯穿疾病发展的全过程.发热是外感热病阳证的特有表现,根据张仲景的六经辨证,阳证可分为三阳证,即太阳证、少阳证、阳明证.太阳证为表证,阳明证为里证,少阳证为半表半里之证.新冠肺炎发病急骤,进展迅速,患者就诊时,可能处于太阳证期,表现为恶寒发热;也可能病邪直中阳明,表现为高热神昏;也可能太阳、少阳、阳明合病,表现为三阳证同时出现.临床治疗时,需针对性地进行治疗.三阳合病虽然为三阳同时发病,但治疗需各有侧重.当戾气偏重于某经时,虽然合并有他经症状,治疗时仍以受邪较重之经为主,兼顾他经.也可先解一经之邪,若他经邪气未解,再根据病势依次治疗.若患者病情较重,三阳并病,亦可三经兼顾,三阳合治.

新型冠状病毒肺炎(corona virus disease 2019,COVID-19)的病原体为新型冠状病毒,人群普遍易感,部分患者病情传变迅速.中医“治未病”思想的核心内涵为:“未病先防、既病防变、瘥后防复”,适用于传染病防治的各个阶段.周明军老先生依据国家中医药管理局预防传染性非典型肺炎参考中药处方五,微调几味中药的剂量,用于新型冠状病毒肺炎的预防.微调后药物组成:生黄芪7 g,白术12 g,防风9 g,苍术9 g,藿香10 g,沙参7 g,金银花15 g,贯众10 g.该方包括玉屏风散原方,既益气固表,又祛风散邪,适用于易感人群.外用方剂为周老先生用于预防流行性感冒的方药,药物组成:八角茴香40 g,肉桂20 g,甘草20 g,白芷20 g,苍术20 g,藿香20 g,制为香囊,于枕边、胸前各放一个.该方具藿香正气散之方义,有治疗山岚瘴疟之功效,孕妇不建议使用.

中医药防治肿瘤有数千年历史,且疗效确切.中医药防治肿瘤,以中医理论为指导,采用辨证论治,通过中药复方,在干预癌前病变、提高肿瘤患者生活质量、预防转移复发、抗肿瘤多药耐药、减毒增效、带瘤生存等方面发挥重要作用,充分体现了整体调节的优势和特色.本文结合中医药防治肿瘤的优势与特色,提出中医药防治肿瘤面临新的发展契机;基于本学科特点和学术研究方向,界定中医肿瘤学科的内涵与外延,提出以"融合、创新"为中医肿瘤学科发展的切入点,加强中医理论研究和临床应用研究为中医肿瘤学科发展和复兴的前提.

网络药理学是融合系统生物学、网络生物学、计算生物学、多向药理学、分子药理学、分子动力学等多学科技术和内容,构建和整合“疾病-表型-基因-药物”多层次网络,分析药物在网络中与特定节点的相互作用关系,从系统、整体角度探索药物与机体相互作用的一门新学科.该学科为中药复方多靶点、多成分、整体性、系统性作用机制研究提供了强力的技术支撑,有助于揭示中药复方科学内涵、发现药物靶标、指导中药新药研发、传承和发展中医药理论.

肠道菌群是由细菌、古细菌、真菌、原生动物和所有哺乳动物肠道内的病毒组成的一个多样化的联合体.正常情况下肠道菌群保持稳态,体内外环境的改变可能会造成肠道菌群失调,结肠癌的发生发展与肠道菌群失调关系密切.国医大师周仲瑛教授根据其六十余年临床实践,于20世纪90年代率先提出“癌毒”病机理论,认为癌毒是肿瘤发生发展的关键病机,在癌毒病机理论指导下,结合临床实践,创制了抗肿瘤有效中药复方消癌解毒方.文章就近年来国内外关于肠道菌群失调与结肠癌发生、发展研究的有关热点问题及治疗进行概述,提出肠道菌群失调与癌毒理论的相关性,并指出从肠道菌群失调角度进一步研究癌毒病机理论生物学基础的可行性.

Objective:To study the effect of Xiaoai Jiedu formula on the proliferation of human hepatocarcinoma SMMC-7721 cells and expression profiles of microRNA (miR)-25-3p,miR-29a-5p,miR-122-3p,miR-124-3p and miR-182-5p.Method:Twelve male white rabbits were randomly divided into four groups.They were respectively given high-dose,middle-dose and low-dose Xiaoai Jiedu formula or normal saline for four days.Serum was taken from their carotid blood and then made into culture medium.Cytotoxicity of Xiaoai Jiedu formula against SMMC-7721 cells was measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-Htetrazolium bromide (MTT) assay.Expression profiles of miR-25-3p,miR-29a-Sp,miR-122-3p,miR-124-3p and miR-182-5p of SMMC-7721 cells were analyzed by a miRNA array and Real-time polymerase chain reaction (Realtime PCR).Result:High-dose,middle-dose and low-dose Xiaoai Jiedu formula could all inhibit the proliferation of SMMC-7721 cells after 12,24,48 h.Xiaoai Jiedu formula gradually increased the proliferation inhibition rate of SMMC-7721 cells in a dose-dependent manner,with the increase of drug concentration.The absorbancy of the high-dose group showed statistical differences after 12 h and 48 h compared with blank control group at the same time points (P ＜ 0.05).The absorbancy of the high-dose group showed statistically significant differences after 24 h compared with the blank control group at the same time point (P ＜ 0.01).The absorbancy of the high dose group after intervention for 24 h was significantly lower than that of blank control group (P ＜ 0.01),the group's inhibition rate was 42.86％.Moreover,Real-time PCR verified the down-regulation of miR-25-3p,miR-182-Sp and the up-regulation of miR-29a-5p,miR-122-3p,miR-124-3p induced by Xiaoai Jiedu formula.The regulatory effect of the high-dose group was more significant than that of the blank control group (P ＜ 0.01).Conclusion:Xiaoai Jiedu formula may inhibit the proliferation of SMMC-721 by inducing the change in microRNA (miRNA) expression.However,the concrete mechanism remains to be further studied.

Objective:To study the expression of miR-34a in A549 cell of non-small cell lung cancer,relationship between miR-34a and Met signaling pathway,and reveal the possible anticancer mechanism of OPB.Methods:On the base of A549 cells,MRC-5 cells and A549 + OPB cells,the expressions of miR-34a in these cell lines were detected by qRT-PCR method.MTT method was used for deteting the proliferation inhibition.The downstream targets of miR-34a were predicted by bioinformatics software.The impact of miR-34a and OPB on Met was verified by Western Blot technique on the protein level.Results:The qRT -PCR results showed that the expression quantity of miR-34a in MRC-5 cells was significantly higher than that in A549 cells and A549 + OPB cells.Proliferation of A549 cells were inhibited after transfected miR-34a.TargetScan bioinformatics software indicated Met is one of downstream targets of miR-34a,and confirmed the results of the experimental results from fluorescein report.The expression of miR-34a was increased and the expression of Met was decreased in the transfected A549 cell and A549+ OPB cell compared to the un-transfected A549 cell.Conclusion:In non-small cell lung cancer,OPB may up-regulate the expression of miR-34a,thereby inhibiting target gene Met to play a role of anti-cancer.

ObjectiveTo investigate the effects of gallic acid on the invasion of gastric cancer cell line MGC-803 and to explore the underlying mechanism.MethodsMGC-803 cells were cultured with different concentrations of gallic acid in vitro,and MTT assay was used to evaluate the survival rate of cells.Cell invasion capabilities were evaluated by means of transwell matrix penetration assays.Expression levels of PI3K/AKT signaling pathway-related factors (PI3K,p-PI3K,AKT,p-AKT)and invasion-related proteins of matrix-metallopeptidase-2(MMP2)and MMP9 were analyzed by Western blotting method.ResultsGallic acid at 6.250-50.000μmol·L-1 caused concentration- dependent inhibition of the proliferation of MGC-803 cells(P<0.05).MGC-803 cells treated with gallic acid showed significantly decreased invasion capabilities(P<0.05).Western blotting results demonstrated that gallic acid inhibited the protein expression levels of p-PI3K,p-AKT,MMP2 and MMP9 in MGC-803 cells.Moreover,PI3K inhibitors can inhibit the activation of PI3K/AKT signaling pathway and the expression of MMP2 and MMP9.ConclusionGallic acid plays a role in inhibiting the invasion activity of gastric cancer cell line MGC-803,and the mechanism is probably related to suppressing the expression of MMP2 and MMP9 through regulating PI3K/AKT signaling pathway.

目的:本研究主要观察不同方式处理后的非小细胞肺癌(NSCLC)A549细胞中miRNA-34b表达水平,探讨miRNA-34b对MET信号通路的调控机制,以及麦冬皂苷B(OPB)抑癌效应的分子机理,探寻治疗NSCLC的新靶点.方法:采用非小细胞肺癌A549细胞、胚肺成纤维细胞MRC-5、A549+OPB细胞、感染过表达慢病毒LV-hsa-mir-34b的A549细胞、以及感染阴性对照CON181B病毒的A549细胞作为研究对象,分别设为CON组、MRC-5组、CON+OPB组、Micro-up组、NC组.采用qRT-PCR方法检测miR-34b在CON组、MRC-5组、A549+OPB组A549细胞中的表达情况.使用生物信息学软件预测miRNA-34b可能的下游功能靶基因.使用qRT-PCR的方法定量分析OPB对MET基因表达的影响,用Western blot检测miRNA-34b和OPB对靶MET蛋白表达的影响.结果:与MRC-5组相比,A549细胞中miRNA-34b的表达明显减少,加入OPB后miR-34b的表达增加.生物信息学预测显示MET基因是miR-34b可能的关键下游靶基因.加入OPB后,MET基因水平和蛋白水平的表达均降低.结论:OPB可能通过上调A549细胞miRNA-34b表达,抑制下游靶基因MET进而发挥抗癌作用.

微小核糖核酸(miRNA)是一类广泛存在的非编码蛋白的小分子单链RNA,通过转录后水平调节基因的表达,进而调节细胞的代谢、增殖、分化和凋亡等基本生理过程.miRNA是表观遗传主要研究领域之一,是近几年来生命科学新的研究热点之一.miRNA表达及调控失衡在肿瘤的发生、发展中发挥重要作用.在中医药抗肿瘤研究中,miRNA表达及调控为诠释中医基本理论、阐明中医药抗肿瘤作用机制提供了新的研究思路.miRNA成为中医药防治恶性肿瘤新的靶标.

目的 观察消癌解毒方对大鼠W256癌肉瘤抑制作用及其生存改善作用.方法 W256癌肉瘤大鼠随机分为空白组、模型组、顺铂治疗组和消癌解毒方高、中、低剂量治疗组,观察大鼠生存期、体质量、摄食量、计算抑瘤率,采用酶联免疫分析法测定大鼠血清中TNF-α、TGF-β的含量.结果 消癌解毒方能抑制瘤体生长(P＜0.05～0.01),延长荷瘤大鼠生存时间(P＜0.05～0.01),改善恶液质状态并以高剂量中药组疗效最优.此外消癌解毒方还能显著降低荷瘤大鼠血清中TNF-α、TGF-β的含量(P＜0.05～0.01).结论 消癌解毒方能抑制肿瘤生长,延长大鼠生存期的作用,其疗效可能与其免疫调节作用有关.

目的:采用代谢组学方法检测W256移植瘤大鼠血浆内源性代谢物异常变化及消癌解毒方对移植瘤大鼠代谢紊乱的调节作用,寻找移植瘤生长可能的生物标志物,探索消癌解毒方代谢性作用机制.方法:采用Wistar大鼠腹腔接种Walker-256瘤株制作腹水瘤模型,移植至大鼠腋下,成移植瘤模型;大鼠分为消癌解毒方低、中、高剂量组和模型组、空白组,收集给药后的第1,6,11天的血浆,采用GC-MS联用仪对血浆中内源性分子进行测定,采用偏最小二乘法判别分析对多变量数据进行分析并建立模型,结合数据库进行代谢物鉴定,进行t检验组间比较,并分析关联代谢通路变化.结果:与空白组相比,模型组大鼠在第11天时,有30个化合物发生了显著变化,给予消癌解毒方后,有10种内源性物质得到了不同程度的转归.结论:血浆中有30种内源性物质与W256肉瘤的生长密切相关,消癌解毒方可使造模后大鼠血浆中异常变化的化合物水平有不同程度的恢复,这10种化合物可能是该复方作用靶点,其发挥药效作用可能与调节相关代谢途径有关.

目的 研究没食子酸(gallic acid,GA)体外诱导人肝癌SMMC-7721细胞凋亡及其作用机制.方法 体外培养人肝癌SMMC-7721细胞,噻唑蓝(MTF)法观察细胞增殖;Hoechst-33258、AnnexinⅤ-FITC/PI检测细胞凋亡情况;逆转录聚合酶链式反应(RT-PCR)法研究凋亡抑制基因Survivin mRNA的变化.结果 6.25 ～ 50 μmol· L-1 GA可抑制SMMC-7721细胞的生长,并呈剂量依赖性;不同剂量的GA作用48 h后,SMMC-7721细胞出现明显的凋亡形态,细胞凋亡率有显著的剂量依赖性.RT-PCR法检测结果显示,GA能明显抑制肝癌细胞中Survivin mRNA的表达.结论 GA可抑制人肝癌SMMC-7721细胞的增殖,这可能与下调凋亡抑制基因Survivin有关.

Aim To investigate the proliferative effect and the apoptosis of human hepatoma SMMC-7721 cells induced by gallic acid ( GA ) , and its underlying mechanism. Methods SMMC-7721 cells were cul-tured in vitro. MTT assay was used to observe the pro-liferation of SMMC-7721 cells induced on GA 24 , 48 , 72 h. The morphological and ultra structural changes of the SMMC-7721 cells were observed by inverted micro-scope and transmission electron microscope respective-ly. Annexin V-FITC/PI staining was used to quantify the percentages of apoptosis in the total cell popula-tion. The expression of p53 mRNA was investigated by RT-PCR. Western blot was used to determine the pro-tein expression of p53. Results GA(6. 25~50 μmol ·L-1 ) markedly inhibited the activity of proliferation and induced apoptosis of SMMC-7721 cells after 48 h in a dose-dependent manner. GA significantly induced cell nuclear condensation and fragmentation. RT-PCR and Western blot results showed that GA could improve the expression of p53 mRNA and protein. Conclusion GA can inhibit the proliferation of human hepatoma SMMC-7721 cells and induce cells apoptosis. The mechanism may be associated with improving tumor suppressor gene p53 expression.