Intestinal macrophages are the main participants of intestinal immune homeostasis and intestinal inflammation. Under different environmental stimuli, intestinal macrophages can be polarized into classical activated pro-inflammatory phenotype (M1) and alternative activated anti-inflammatory phenotype (M2). Its different polarization state is the “guide” to promoting the development and regression of inflammation. Under normal circumstances, intestinal macrophages can protect the intestine from inflammatory damage. However, under the influence of some genetic and environmental factors, the polarization imbalance of intestinal M1/M2 macrophages will lead to the imbalance in the regulation of intestinal inflammation and transform the physiological inflammatory response into pathological intestinal injury. In UC patients, the disorder of intestinal inflammation is closely related to the imbalance of intestinal M1/M2 macrophage polarization. Therefore, restoring the balance of M1/M2 macrophage polarization may be a potentially valuable therapeutic strategy for UC. Evidence has shown that traditional Chinese medicine (TCM) has positive therapeutic effects on UC by restoring the balance of M1/M2 macrophage polarization. This review summarizes the clinical evidence of TCM for UC, the vital role of macrophage polarization in the pathophysiology of UC, and the potential mechanism of TCM regulating macrophage polarization in the treatment of UC. We hope this review may provide some new enlightenment for the clinical treatment, fundamental research, and research and development of new Chinese medicine of UC.

/pdf/a-potential-therapeutic-target-in-traditional-chinese-3do5ra6r.pdf

A potential therapeutic target in traditional Chinese medicine for ulcerative colitis: Macrophage polarization

An animal model of DSS-induced UC has been widely used in basic research, and the dysbiosis of gut microbiome is one of the important pathogenetic mechanisms of DSS-induced UC, but its dynamic changes and correlation with inflammatory factors are not clear yet.Clinical signs and tissue damage degree of C57BL/6 ulcerative colitis mice model induced by different concentrations of DSS were compared with that of normal mice, and finally the optimal concentration of DSS was determined. Then we analyzed the sequencing results of gut microbiome and inflammatory factors to determine the dynamic patterns of gut microbiome and their correlation with the inflammatory factors.DSS at 2.5% and 3.0% concentration could cause intestinal injury and induce colitis. However, 3.0% DSS resulted in higher mortality. In addition, there were dynamic changes of gut microbiome in DSS-induced UC model: the relative abundance of intestinal flora increased first and then decreased in Bacteroides, Parabacteroides, Romboutsia, Clostridium_sensu_stricto_1, Lachnospiraceae_NK4A136_group, norank_f_norank_o_Clostridia_UCG-014, Parasutterella, and decreased first and then increased in Lactobacillus, Muribaculum, norank_f_Muribaculaceae, in addition, Bifidobacterium, Coriobacteriaceae_UCG-002 and Enterorhabdus did not change in the first 14 days but increased significantly on day 21. Moreover, inflammatory cytokines were closely associated with the imbalance of the intestinal microbiota in mice with UC: most pathogenic bacteria in the intestinal tract of the UC animal model were positively correlated with pro-inflammatory factors and negatively correlated with anti-inflammatory factors, while beneficial bacteria were the opposite.Intestinal microecology plays an important role in DSS-induced UC model, and the relative abundance of gut microbiome changes dynamically in the occurrence and development of ulcerative colitis. 

Dynamic Changes in Gut Microbiome of Ulcerative Colitis: Initial Study from Animal Model

Ulcerative colitis (UC), characterized by syndromes including abdominal pain, bloody stool, diarrhea, weight loss, and repeated relapse, is a non-specific inflammatory intestinal disease. In recent years, with the changing dietary habits in China, the incidence of UC has shown an upward trend. UC belongs to the category of recorded as “diarrhea,” “chronic dysentery,” and “hematochezia” in traditional Chinese medicine (TCM), and Shenling BaiZhu powder (SLBZP) is one of the most effective and commonly used prescriptions. In this review, we aim to systematically summarize the clinical application and pharmacological mechanism of SLBZP in the treatment of UC to provide a theoretical basis for its clinical use and experimental evaluation of SLBZP. Our results showed that both SLBZP and SLBZP in combination with chemical drugs, have a significant therapeutic effect against UC with few adverse reactions. Furthermore, combined therapy was better than western medicine. Further, pathophysiological studies indicated that SLBZP has anti-inflammatory, immunomodulatory, antioxidant effects, regulation relative cell signal transduction and regulation of gut microbiota. Although evidence suggests superior therapeutic efficacy of SLBZP for treating UC and the relative mechanism has been studied extensively, various shortcomings limit the existing research on the topic. There is a lack of UC animal models, especially UC with TCM syndromes, with no uniform standard and certain differences between the animal model and clinical syndrome. The dosage, dosage form, and therapeutic time of SLBZP are inconsistent and lack pharmacological verification, and clinical trial data are not detailed or sufficiently rigorous. In addition, SLSZP is composed of multiple Chinese drugs that contain massive numbers of ingredients and which or several components contribute to therapeutic effects. How they work synergistically together remains unknown. Therefore, on the one hand, large sample prospective cohort studies to clarify the clinical efficacy and safety of SLBZP in the treatment of UC are needed. In contrast, researchers should strengthen the study of the molecular biological mechanism of active ingredients and its synergistic actions, clarifying the mechanism of SLBZP in treating UC by multi-component, multi-target, and multi-pathway.

/pdf/traditional-chinese-medicine-prescription-shenling-baizhu-224zcqd0.pdf

Traditional Chinese medicine prescription Shenling BaiZhu powder to treat ulcerative colitis: Clinical evidence and potential mechanisms

The pharmacological validation of the Xiao-Jian-Zhong formula against ulcerative colitis by network pharmacology integrated with metabolomics.

Damage to the intestinal mucosal barrier play an important role in the pathogenesis of ulcerative colitis (UC). Discovering the key regulators and repairing the disturbed barrier are crucial for preventing and treating UC. Traditional Chinese medicine (TCM) has been proved to be effective on treating UC and has exhibited its role in repairing the intestinal mucosal barrier. We summarized the evidence of TCM against UC by protecting and repairing the physical barrier, chemical barrier, immune barrier, and biological barrier. Mechanisms of increasing intestinal epithelial cells, tight junction proteins, and mucins, promoting intestinal stem cell proliferation, restoring the abundance of the intestinal microbiota, and modulating the innate and adaptive immunity in gut, were all involved in. Some upstream proteins and signaling pathways have been elucidated. Based on the existing problems, we suggested future studies paying attention to patients’ samples and animal models of UC and TCM syndromes, conducting rescue experiments, exploring more upstream regulators, and adopting new technical methods. We hope this review can provide a theoretical basis and novel ideas for clarifying the mechanisms of TCM against UC via repairing the intestinal mucosal barrier.

Repairing the intestinal mucosal barrier of traditional Chinese medicine for ulcerative colitis: a review

Purpose Developed a preoperative prediction model based on multimodality imaging to evaluate the probability of inferior vena cava (IVC) vascular wall invasion due to tumor infiltration. Materials and methods We retrospectively analyzed the clinical data of 110 patients with renal cell carcinoma (RCC) with level I-IV tumor thrombus who underwent radical nephrectomy and IVC thrombectomy between January 2014 and April 2019. The patients were categorized into two groups: 86 patients were used to establish the imaging model, and the data validation was conducted in 24 patients. We measured the imaging parameters and used logistic regression to evaluate the uni- and multivariable associations of the clinical and radiographic features of IVC resection and established an image prediction model to assess the probability of IVC vascular wall invasion. Results In all of the patients, 46.5% (40/86) had IVC vascular wall invasion. The residual IVC blood flow (OR 0.170 [0.047-0.611]; P = 0.007), maximum coronal IVC diameter in mm (OR 1.203 [1.065-1.360]; P = 0.003), and presence of bland thrombus (OR 3.216 [0.870-11.887]; P = 0.080) were independent risk factors of IVC vascular wall invasion. We predicted vascular wall invasion if the probability was >42% as calculated by: {Ln [Pre/(1 - pre)] = 0.185 × maximum cornal IVC diameter + 1.168 × bland thrombus-1.770 × residual IVC blood flow-5.857}. To predict IVC vascular wall invasion, a rate of 76/86 (88.4%) was consistent with the actual treatment, and in the validation patients, 21/26 (80.8%) was consistent with the actual treatment. Conclusions Our model of multimodal imaging associated with IVC vascular wall invasion may be used for preoperative evaluation and prediction of the probability of partial or segmental IVC resection.

/pdf/a-predictive-model-for-tumor-invasion-of-the-inferior-vena-2nwrwe4693.pdf

A Predictive Model for Tumor Invasion of the Inferior Vena Cava Wall Using Multimodal Imaging in Patients with Renal Cell Carcinoma and Inferior Vena Cava Tumor Thrombus.

Pharmacological mechanism of Shenlingbaizhu formula against experimental colitis.

Molecular pathology assists the diagnosis of lymphoepithelial sialadenitis, Sjögren's syndrome and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue

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A Predictive Model for Tumor Invasion of the Inferior Vena Cava Wall Using Multimodal Imaging in Patients with Renal Cell Carcinoma and Inferior Vena Cava Tumor Thrombus.

Pharmacological mechanism of Shenlingbaizhu formula against experimental colitis.

Molecular pathology assists the diagnosis of lymphoepithelial sialadenitis, Sjögren's syndrome and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue