The pathogenesis and treatment of colorectal cancer (CRC) continue to be areas of ongoing research, especially the benefits of traditional Chinese medicine (TCM) in slowing the progression of CRC. This study was conducted to investigate the effectiveness and mechanism of action of modified Lichong decoction (MLCD) in inhibiting CRC progression. We established CRC animal models using azoxymethane/dextran sodium sulfate (AOM/DSS) and administered high, medium, or low doses of MLCD or mesalazine (MS) for 9 weeks to observe MLCD alleviation of CRC. The optimal MLCD dose group was then subjected to metagenomic and RNA sequencing (RNA-seq) to explore the differentially abundant flora and genes in the control, model and MLCD groups. Finally, the mechanism of action was verified using WB, qRT‒PCR, immunohistochemistry and TUNEL staining. MLCD inhibited the progression of CRC, and the optimal effect was observed at high doses. MLCD regulated the structure and function of the intestinal flora by decreasing the abundance of harmful bacteria and increasing that of beneficial bacteria. The differentially expressed genes were mainly associated with the Wnt/β-catenin pathway and the cell cycle. Molecular biology analysis indicated that MLCD suppressed the Wnt/β-catenin pathway and the epithelial–mesenchymal transition (EMT), inhibited abnormal cell proliferation and promoted intestinal epithelial cell apoptosis. MLCD mitigated the abnormal growth of intestinal epithelial cells and promoted apoptosis, thereby inhibiting the progression of CRC. This inhibition was accomplished by modifying the intestinal microbiota and disrupting the Wnt/β-catenin pathway and the EMT. Therefore, MLCD could serve as a potential component of TCM prescriptions for CRC treatment.

Colon polyps are closely related to the occurrence of colon cancer. With the change of living environment,the incidence rate of the disease increases year by year. At present, endoscopic resection is the main treatment of colonic polyps in western medicine, but there is a certain probability of recurrence. The author followed professor LI Dian-gui, a master of traditional Chinese medicine, to analyze and summarize professor LI Dian-gui’s ideas on the treatment of colon polyps. Professor LI Dian-gui believes that the key pathogenesis of colonic polyps is the accumulation of turbid toxin. In the clinical treatment, the treatment method is to remove turbid toxin. According to the patient’s symptoms, signs and pathological results of enteroscopy,combined with the treatment methods of strengthening the spleen, regulating qi, eliminating phlegm and dispersing blood stasis,it has achieved good clinical efficacy. And the case demonstrates professor LI Dian-gui’s clinical thinking and medication characteristics of treating colonic polyps based on turbid toxin theory.

Ulcerative colitis (UC) is a chronic and immune-mediated inflammatory disorder characterized by abdominal pain, diarrhoea, and haematochezia. The goal of clinical therapy for UC is mucosal healing, accomplished by regenerating and repairing the intestinal epithelium. Paeoniflorin (PF) is a natural ingredient extracted from Paeonia lactiflora that has significant anti-inflammatory and immunoregulatory efficacy. In this study, we investigated how PF could regulate the renewal and differentiation of intestinal stem cells (ISCs) to improve the regeneration and repair of the intestinal epithelium in UC. Our experimental results showed that PF significantly alleviated colitis induced by dextran sulfate sodium (DSS) and ameliorated intestinal mucosal injury by regulating the renewal and differentiation of ISCs. The mechanism by which PF regulates ISCs was confirmed to be through PI3K-AKT-mTOR signalling. In vitro, we found that PF not only improved the growth of TNF-α-induced colon organoids but also increased the expression of genes and proteins related to the differentiation and regeneration of ISCs. Furthermore, PF promoted the repair ability of lipopolysaccharide (LPS)-induced IEC-6 cells. The mechanism by which PF regulates ISCs was further confirmed and was consistent with the in vivo results. Overall, these findings demonstrate that PF accelerates epithelial regeneration and repair by promoting the renewal and differentiation of ISCs, suggesting that PF treatment may be beneficial to mucosal healing in UC patients.

目的 基于网络药理学预测泄浊解毒方治疗溃疡性结肠炎(UC)的活性成分、作用靶点及信号通路,通过动物实验验证其可能的作用机制,为泄浊解毒方的临床应用提供科学依据.方法 基于网络药理学预测得到泄浊解毒方治疗UC的可能作用靶点和通路.随机选取10只SD大鼠设为空白组(Con),其余通过三硝基苯磺酸(TNBS)/乙醇复合灌肠法建立UC大鼠模型,将造模成功的大鼠分为模型组、美沙拉秦组、泄浊解毒方低、中、高剂量组,药物干预组给予相应的药物灌胃,空白组和模型组给予生理盐水灌胃,连续14 d.给药结束后处死大鼠,苏木素-伊红(HE)法观察各组大鼠结肠黏膜组织形态学变化;酶联免疫吸附法(ELISA)检测大鼠血清中细胞因子白细胞介素-6(IL-6)、白细胞介素-10(IL-10)和白细胞介素-17(IL-17)的含量.蛋白免疫印迹法(WB)检测结肠组织磷脂酰肌醇3-激酶(PI3K)、磷酸化的磷脂酰肌醇3-激酶(p-PI3K)、蛋白激酶B(AKT)、磷酸化的蛋白激酶B(p-AKT)的表达.结果 最终获得泄浊解毒方潜在活性成分94个,核心治疗靶点9个.泄浊解毒方可影响炎症反应调节、活性氧代谢过程,氧化应激反应和白细胞黏附等多个生物过程,KEGG富集分析结果显示泄浊解毒方治疗UC主要涉及PI3K/AKT信号通路、核转录因子-κB(NF-κB)信号通路、肿瘤坏死因子(TNF)信号通路、缺氧诱导因子-1(HIF-1)信号通路、辅助性T细胞17(Th17)细胞分化等多个信号通路.动物实验显示,泄浊解毒方可改善UC大鼠结肠黏膜的炎症反应,降低UC大鼠血清中促炎细胞因子IL-6、IL-17的含量,升高抑炎细胞因子IL-10的含量.泄浊解毒方可降低UC大鼠结肠组织p-PI33K、p-AKT蛋白的表达.结论 泄浊解毒方可通过参与炎症反应调节、活性氧代谢过程,氧化应激反应和白细胞黏附等多个生物过程,调节炎性细胞因子,抑制PI3K/AKT信号通路,进而改善UC大鼠的炎症反应.

Aim To predict the targets of Modified Danggui Shaoyao San（MDSS） in the treatment of chronic atrophic gastritis（CAG） based on network pharmacology and vertify the results based on experimention. Methods TCMSP,SWISS TARGETS,GENE CARDS and OMIM databases were used to screen the therapeutic targets of MDSS for CAG. STRING database and Cytoscape software were used to construct the protein interaction network and screen the core targets. Metascape database was used for GO analysis and KEGG enrichment pathways. And molecular docking was used for target validation. CAG rat model was prepared by N-methyl-N′-nitroso-N-nitroguanidine free drink combined with sodium salicylate gastric lavage. The pathology of rat gastric mucosa was observed by hematoxylin-eosin staining, and the ultrastructure of epithelial cells was observed by transmission electron microscopy. The serum IL-6 and IL-10 content was detected by enzyme-linked immunosorbent assay, and the expression of JAK2,STAT3,p-STAT3,c-MYC mRNA and protein in rats was detected by qPCR and Western blot. Results MDSS acted on 189 targets, mainly involved in response to oxidative stress and apoptotic signaling pathway. KEGG analysis related to pathways in cancer and JAK-STAT signaling pathway. The experimental results showed that the MDSS could improve the degree of atrophy of gastric mucosa in CAG rats and improve the status of epithelial cells, down-regulate the serum IL-6 content of CAG rats, up-regulate the IL-10 content, and reduce the expression of JAK2,STAT3,p-STAT3,c-MYC mRNA and protein in gastric mucosa with statistical significance. Conclusions MDSS treats CAG through multiple active ingredients, targets, and pathways, the mechanism of which may be related to the inhibition of the JAK2/STAT3 signaling pathway.

总结李佃贵基于浊毒理论从脾胃防治结直肠腺瘤进展为结直肠癌的经验.李佃贵认为脾胃失和、功能异常,痰、湿、瘀、滞、虚等相继产生,损伤肠络,导致腺瘤发生.各种病理产物胶着日久,化为浊毒之邪.浊毒伏匿是促进腺瘤进展为腺癌的关键.治疗当以调脾胃、化浊毒为大法,分别予行气畅中除浊毒、活血理脾消浊毒、化痰运脾涤浊毒、扶正益中散浊毒等治法阻断腺瘤进展,以降低其癌变率,临床疗效显著.附医案2则以佐证.

张锡纯认为胃气以降为顺,胃气不降导致胃痞发生,而胃气不降之关键在于五脏功能失常,即心肺阳虚、肝脾失调、肾虚冲逆皆可引起胃气不降而致胃痞.据此,张锡纯认为应从五脏论治胃痞,提出通降胃气、宣通心肺、行气利湿、升肝扶脾、纳肾降冲等治法,并自拟理饮汤、升降汤、理痰汤等方,灵活运用生赭石、厚朴、清半夏、桂枝、茵陈、生麦芽、白术等药物,值得学习借鉴.

目的:基于文献分析中药自拟方治疗痰瘀互结型非酒精性脂肪性肝病(Non-alcoholic Fatty Liver Disease,NAFLD)的用药规律,为临床治疗痰瘀互结型NAFLD提供参考.方法:在中国知网数据库、万方数据库、维普数据库中分别以“非酒精性脂肪肝痰瘀互结”“非酒精性脂肪肝痰瘀”为主题词,共检索出文献914篇,严格按照纳入排除标准筛选,得出符合条件的文献39篇.结果:共纳入符合标准的文献39篇,治疗痰瘀互结型NAFLD的方剂39首,涉及87味中药,共使用416次.其中使用频率位于前10位的药物依次为:山楂、丹参、泽泻、柴胡、茯苓、决明子、甘草、郁金、白术、半夏.以活血化瘀药、补虚药、利水渗湿药、清热药和理气药为主,药味多为苦、甘、辛,药性多为寒、温,药物归经主要为肝经和脾经.结论:该研究通过数据统计分析结果表明,自拟方治疗NAFLD的用药规律体现了以疏肝、健脾、化痰、活血为主的治法.聚类分析能更好地分析药对组合和组方规律.