Ulcerative colitis (UC) is a chronic and recurrent inflammatory intestinal disorder characterized by gut dysbiosis, but effective strategies are currently limited. Here, we demonstrated that Agrimoniae Herba Polysaccharides (AHP), the key active components of a herb widely used for intestinal inflammation in East Asia countries, significantly reversed colitis-related phenotypes in a gut microbiota dependent, as antibiotic treatment abolished its therapeutic effect, while gut microbes from AHP-treated mice reproduced the anti-inflammatory effect. Bacterial 16S rRNA sequencing analysis showed AHP greatly reshaped the overall structure of microbiota, especially boosting colonization of Faecalibaculum rodentium (F. rodentium), which led to a significant alleviation of intestinal inflammation, accompanied by the promotion of CD4+ T cell differentiation toward Treg. Additionally, we identified quinic acid as a key metabolite of F. rodentium enriched by AHP treatment, and found that it induced the differentiation of naïve CD4+T cells sorted from UC patients into Treg cells in vitro, which correlated with the enhancement of TAZ/Foxp3 acetylation axis. Collectively, our results show that AHP exerts the beneficial effects in the treatment of UC by acting as a prebiotic to enrich the commensal bacterium F. rodentium, and offer a novel microbiota-dependent strategy for inflammatory bowel disease.

Nonalcoholic fatty liver disease (NAFLD) is a growing health burden worldwide. The association between blood selenium (Se) and NAFLD in naturally menopausal women remains unclear. This study aimed to evaluate the association of blood Se levels with the prevalence of NAFLD, hepatic steatosis, and liver fibrosis in the US naturally menopausal women population. This study analyzed the dataset from the 2017 to 2018 National Health and Nutrition Examination Survey, including 595 naturally menopausal women. Weighted logistic regression models were used to evaluate the cross-sectional association between blood Se levels and the prevalence of NAFLD. Linear regression and ordinal logistic regression were used to evaluate the association between blood Se levels and liver steatosis and fibrosis. All analyses were conducted using the R survey package. There were no significant associations of blood Se levels with NAFLD in 3 adjusted models (odds ratio [OR] = 0.52, 95% confidence interval [CI], 0.04-7.11; OR = 0.66, 95% CI, 0.04-9.82; OR = 0.79, 95% CI, 0.08-8.08). However, in the fully adjusted model, blood Se levels showed a negative association with liver fibrosis (β = -2.32, 95% CI, -4.21, -0.43). Participants were divided into quartiles (Q1-Q4) based on the distribution of blood Se concentrations within the study cohort. The specific cutoff points were Q1 group (<173.67 μg/L), Q2 group (173.67 to <189.15 μg/L), Q3 group (189.15 to <204.35 μg/L), and Q4 group (≥204.35 μg/L). Compared with the reference group (Q1 group, <173.67 μg/L), significant inverse associations were also found for the higher Se groups (Q3 group: OR = 0.23, 95% CI, 0.1-0.53; Q4 group: OR = 0.28, 95% CI, 0.12-0.66). Our results showed that blood Se levels were not significantly associated with the prevalence of NAFLD in a US population of naturally menopausal women, but higher blood Se levels were negatively associated with liver fibrosis. Further research is needed to assess the causal relationship between exposure and disease risk.

Tissue-resident memory T (TRM) cells are a type of tissue-restricted memory T cells with terminal differentiation and a memory function. They exist in mucosal tissues for a long period. In the absence of disease, TRM cells promote essential inflammation, which reinforces the intestinal barrier and prevents bacterial translocation. However, in inflammatory or autoimmune environments, TRM cells are hyperactivated. This heightened activity causes the host to release excessive pro-inflammatory cytokines, resulting in local immune imbalances and damage to the barrier, ultimately leading to tissue lesions. Numbers of studies have shown that TRM cells play a crucial role in the development and progression of inflammatory bowel disease (IBD), suggesting that targeted regulation of TRM cells homeostasis may be an important strategy for treating IBD. Here, we compiled the existing understanding of the role of TRM cells in IBD, with particular emphasis on the associated mechanisms and approaches for targeting TRM cells in IBD treatment. This review will serve as a foundation for a better understanding of IBD development and enhancing the effectiveness of clinical treatments for IBD.

BACKGROUND:Non-alcoholic steatohepatitis (NASH) is an important clinical issue and a challenge in the field of global public health. However, there are very few clinically approved drugs that can effectively treat NASH. Rhein is a natural organic compound with anti-inflammatory and antioxidant properties, but the specific role and mechanism on NASH remain unexplored. PURPOSE:This study investigated the role and associated mechanism of rhein in NASH mice. METHODS:The effects of rhein on lipid accumulation were evaluated in NASH mice through systemic signs of obesity, biochemical parameters, and histological changes. Network pharmacology was employed to determine the main bioactive compounds and key targets of rhein for the NASH treatment. Additionally, antibiotics treatment and fecal microbiota transplantation (FMT) were performed to investigate the role of microbiota in the treatment of NASH with rhein. Bacterial 16S rRNA amplicon sequencing, LC-MS/MS analysis and flow cytometric were employed to investigate the mechanisms underlying rhein's regulatory effects on gut microbiota, BA metabolism and immune balance. Finally, in vitro cell experiments were conducted to explore the effects of metabolites on Th17 cell differentiation. RESULTS:Our results showed that mice treated with rhein showed a significant alleviating effect from high-fat diet (HFD)-induced liver lipid accumulation and pathological changes compared to those in HFD group. The protective effects of rhein are gut microbiota dependent, as demonstrated by fecal microbiome transplantation and antibiotics treatment. Microbiota transferred from rhein-treated mice displayed a similar role in attenuating hepatic lipid deposition as rhein on NASH in mice, and depletion of the gut microbiota through antibiotics treatments diminished the protective effects of rhein on NASH mice. Moreover, the results from bacterial 16S rRNA sequencing suggested that rhein partially attenuated HFD-induced gut dysbiosis in NASH mice. Network pharmacology analyses was implemented and showed that Th17 cell differentiation might be the potential target in the treatment of rhein against NASH, which was confirmed by flow cytometric analysis showing markedly decrease of the percentage of Th17 cells, corresponded with upregulated Treg cells in rhein-treated NASH mice. Furthermore, targeted bile acid metabolomics analysis showed that supplement with rhein greatly increased the levels of primary bile acids β-MCA and AlloLCA, positively correlated with the relative abundances of Bifidobacterium_choerinum, which may play the key role by which rhein-altered gut microbiota promoted the restoration of Th17/Treg balance in NASH mice. Subsequent in vitro experiments confirmed that AlloLCA directly inhibits Th17 cell differentiation, with suppression of glycolysis potentially serving as the underlying mechanism for the immunomodulatory effects of AlloLCA. CONCLUSIONS:Collectively, our results suggested that orally administrated rhein reduced hepatic lipid deposition through the modulation of dysregulated gut microbiota and bile acids metabolism, thus regulating Th17/Treg immune balance. This study uncovers a novel mechanistic axis in NASH pathogenesis and providing new research directions for microbiota-targeted clinical strategies.

The gut microbiota plays a critical role in the occurrence and development of IBS-D, however, IBS-D-associated tongue coating microbiome dysbiosis has not yet been clearly defined. To address this, we analyzed the structure and composition of the tongue coating microbiome in 23 IBS-D patients and 12 healthy controls using 16S rRNA high-throughput sequencing analysis. The 16S rRNA sequencing results revealed that the overall observed OTUs of tongue coating microbiome in IBS-D patients exhibited a significant decrease compared with the healthy controls. Alpha diversity analysis showed that the diversity and community richness were significantly reduced in IBS-D patients, and PCoA revealed a distinct clustering of tongue coating microbiome between the IBS-D patients and healthy controls. Microbial comparisons at the genus level showed that the abundance of Veillonella, Prevotella in IBS-D patients was higher than those in healthy controls, while Streptococcus, Haemophilus, Granulicatella, and Rothia were significantly reduced compared with the healthy volunteers. Functional analysis results showed significant differences in 88 functional metabolic pathways between the IBS-D patients and the healthy controls, including fatty acid biosynthesis. These findings identified the structure, composition, functionality of tongue coating microbiome in IBS-D patients, and hold promise the potential for therapeutic targets during IBS-D management.

Background:Irritable bowel syndrome (IBS), a gastrointestinal motility disorder affecting millions of patients worldwide, has a substantial impact on healthcare economics and patient quality of life. However, fully satisfactory therapeutic options remain lacking. The identification of pathogenic proteins supported by causal genetic evidence enables the exploration of potential therapeutic targets for IBS. Methods:A Mendelian randomization (MR) study was performed to discover potential treatment targets linked to IBS. Summary data for IBS (outcome) were acquired from the two largest independent cohorts: sample sizes of 486,601 (53,400 cases and 433,201 controls) and 101,884 (24,735 cases and 77,149 controls), respectively. Instrumental variables were derived from cis-expression quantitative trait loci (cis-eQTL) data of druggable genes, obtained through the eQTLGen Consortium database. Colocalization analysis was employed to assess whether IBS risk and gene expression were influenced by shared SNPs. An IBS mouse model was additionally utilized to confirm the therapeutic potential of drug targets. Results:Four drug targets (P2RY14, SLC5A6, ATRAID, and IL1RL1) displayed notable MR findings in two separate datasets. Purinergic receptor P2Y14 (P2RY14) and all-trans retinoic acid-induced differentiation factor (ATRAID) exhibited robust evidence of colocalization with IBS. We further showed an abnormal increase in expression of P2RY14 and a significant decrease in ATRAID level in the colon tissue of IBS mice. Conclusion:This study proposes two potential therapeutic targets for IBS: P2RY14 and ATRAID. Drugs aimed at targeting these two genes have a greater chance of success in clinical trials, potentially facilitating the prioritization of IBS drug development and lowering associated costs.

Nonalcoholic steatohepatitis (NASH), an inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), is characterized by liver steatosis, inflammation, hepatocellular injury and different degrees of fibrosis, and has been becoming the leading cause of liver-related morbidity and mortality worldwide. Unfortunately, the pathogenesis of NASH has not been completely clarified, and there are no approved therapeutic drugs. Recent accumulated evidences have revealed the involvement of macrophage in the regulation of host liver steatosis, inflammation and fibrosis, and different phenotypes of macrophages have different metabolic characteristics. Therefore, targeted regulation of macrophage immunometabolism may contribute to the treatment and prognosis of NASH. In this review, we summarized the current evidences of the role of macrophage immunometabolism in NASH, especially focused on the related function conversion, as well as the strategies to promote its polarization balance in the liver, and hold promise for macrophage immunometabolism-targeted therapies in the treatment of NASH.

目的:挖掘现有数据库中中药复方治疗肝郁脾虚证腹泻型肠易激综合征(IBS-D)的用药规律及特点.方法:检索现有文献数据库中所有中药复方加减治疗肝郁脾虚证IBS-D的临床随机对照试验,搜集具有明显疗效的中药复方,将数据进行规范化处理后建立数据库并导入古今医案云平台,通过数据挖掘板块中的统计分析、关联规则分析、复杂网络分析等方法对纳入的方剂进行用药频次统计、药物四气五味及归经分析,并且得出核心组方.结果:共纳入 122 篇文献,包含 122首中药复方,132 味中药.使用频次最多的前5 味中药分别为:防风、陈皮、茯苓、白芍、柴胡.所有中药中平性使用频率最高,其次为温性、微寒及微温.药味以甘味为主,辛味、苦味、酸味、淡味次之.药物归经以脾经为主,其次为肺经、肝经、胃经.结论:肝郁脾虚证IBS-D的治疗应当在疏肝健脾之品中酌加驱散风邪之药,重视寒热的兼证.

Objective: To observe the clinical efficacy of Chinese herb tea on intervention of non-alcoholic fatty liver disease（NAFLD） with damp-heat accumulation type. Methods: A total of 72 NAFLD with damp-heat accumulation type patients were randomly divided into control group and treatment group, with 36 patients in each group. The control group received diet and exercise intervention, and the treatment group added Chinese herb tea on the basis of the control group. The course of treatment of both groups was 12 weeks. The two groups were observed traditional Chinese medicine（TCM） symptom score, controlled attenuation parameter（CAP）, serum alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, total cholesterol（TC）,triglyceride（TG） and traditional Chinese medicine syndrome before and after treatment, and the adverse reactions of the two groups. Results: There was a significant difference in overall response rate between the treatment group and the control group 96.9%（31/32） vs 92.9%（26/28）（P＜0.05）. After treatment, both groups had significant reductions in TCM symptom score,CAP, ALT, AST, TC（P＜0.05） and the treatment group also had significant reductions in TG（P＜0.05）. Compared with the control group, the treatment group had significantly greater reductions in TCM symptom score, CAP（P＜0.05）. No adverse effects were seen in either group during the treatment period. Conclusion: Chinese herb tea can effectively improve the clinical symptoms and liver function of NAFLD with damp-heat accumulation type, reduce the hepatic fat content and blood lipid level,and have high safety.

Objectives:Conventional approaches for patients with nonerosive gastroesophageal reflux disease (NERD) were not satisfactory. This study aimed to evaluate the effectiveness and mechanisms of Chinese herbal medicine Hewei Jiangni Decoction (HWJND) as a novel and promising regimen for NERD.Methods:A total of 128 patients with NERD were randomly assigned to the Treatment group and Control group. The patients from the Treatment group were administered HWJND (81 g) plus dummy omeprazole (20 mg) daily for 8 weeks, and the others were given dummy HWJND granules (81 g) plus omeprazole (20 mg). The clinical efficacy was assessed using the gastroesophageal reflux disease questionnaire (GERD-Q) scale, patient reported outcomes (PRO) scale, and short form health survey 36 (SF-36) scale at week 4. Moreover, its pharmacological and molecular mechanisms were elucidated based on network pharmacology and molecular docking.Results:Due to case shedding and other reasons, 109 patients, including 56 in the Treatment group and 53 in the Control group completed this study. Our results showed that HWJND significantly improved heartburn, regurgitation, epigastric pain, nausea, and sleep disturbance, which led to a significant reduction of GERD-Q scores in NERD patients. In addition, PRO scores of NERD patients with HWJND administration were improved, and sufficient relief of physical role, body pain, general health, social function, and mental health on the SF-36 scale was also observed in patients after HWJND treatment. We further showed that the curative effect of HWJND was close to that of omeprazole, except for the better improvement of general health and social function. What's more, the main active ingredients of HWJND included quercetin, beta-sitosterol, naringenin, baicalein, and kaempferol were retrieved, and the protective effects of HWJND against NERD may be closely related to targets such as TNF, IL6, IL1B, MMP9, CXCL8, and EGFR, which were mainly enriched in IL-17 signaling pathway and TNF signaling pathway.Conclusion:Our findings demonstrate that HWJND is noninferior to oral omeprazole for the treatment of patients with NERD, plays a therapeutic role through multiple targets and diverse pathways, and holds promise for complementary and alternative therapy for the treatment of NERD. This trial is registered with http://www.chictr.org.cn, Chinese Clinical Trials Registry [ChiCTR2200055960].

受环境、生活方式、饮食习惯等因素影响,慢性胃炎已成为消化内科常见病,其中慢性非萎缩性胃炎发病率及复发率高,西医治疗往往难以奏效,且复发率高,药物不良反应大.中医治疗慢性非萎缩性胃炎具有个体化、标本兼治的优势,还可以改善患者体质,从而达到良好的远期治疗效果.谢春娥教授认为本病的发病主要是邪气郁滞中焦导致胃失和降所致,并以开解郁滞、疏通气机为基本治疗原则,随症状改变灵活加减用药,具有良好的临床疗效.文章总结谢春娥教授治疗慢性非萎缩性胃炎的临床经验,并附验案4则,以资佐证.

目的 基于肠-肝轴理论探讨茵陈苓桂剂对高脂饲料诱导的非酒精性脂肪性肝病(NAFLD)大鼠肠黏膜屏障的影响及机制.方法 从60只SD大鼠中随机取10只作为对照组,余大鼠采用高脂饲料建立NAFLD模型.造模成功后,将48只大鼠随机分为5组,茵陈苓桂剂高、中、低剂量组分别给予19.6 g/kg、9.8 g/kg、4.9 g/kg的茵陈苓桂剂灌胃,多烯磷脂酰胆碱组给予0.15 g/kg多烯磷脂酰胆碱灌胃,对照组和模型组给予等体积的蒸馏水灌胃.连续灌胃4周后,HE染色观察各组大鼠肝脏及回肠末端组织病理变化,检测血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、三酰甘油(TG)、总胆固醇(TC)、肿瘤坏死因子(TNF-α)、白细胞介素-6(IL-6)及血浆内毒素(LPS)水平,Western blot法检测回肠组织中TLR4及CD14蛋白表达情况,免疫组织化学法检测回肠组织中紧密连接蛋白ZO-1、Occludin表达情况.结果 与对照组比较,模型组大鼠肝脏和回肠组织可见明显病理损伤,血清ALT、AST、TC、TG、TNF-α、IL-6及血浆LPS水平和回肠组织中TLR4、CD14蛋白相对表达量均明显增高(P均<0.05),回肠组织中ZO-1、Occludin平均光密度值均明显降低(P均<0.05).与模型组比较,多烯磷脂酰胆碱组与茵陈苓桂剂高、中剂量组大鼠血清ALT、AST、TC、TG水平和茵陈苓桂剂低剂量组大鼠血清AST、TC水平均明显降低(P均<0.05);茵陈苓桂剂高剂量组血清AST水平明显低于中剂量组(P<0.05),血清ALT、TC、TG水平均明显低于低剂量组(P均<0.05).与模型组比较,茵陈苓桂剂高剂量组大鼠血清TNF-α、IL-6及血浆LPS水平和茵陈苓桂剂中剂量组血清IL-6水平均明显降低(P均<0.05),各给药组大鼠回肠组织中ZO-1、Occludin蛋白阳性表达均增多,TLR4、CD14蛋白相对表达量均明显降低(P均<0.05),茵陈苓桂剂高剂量组大鼠回肠组织中ZO-1、Occludin蛋白表达平均光密度值均明显升高(P均<0.05).结论 茵陈苓桂剂可改善NAFLD大鼠肝脏炎症,调节脂代谢,修复肠道紧密连接,靶向调控LPS/TLR4信号通路的转导,通过调节肠-肝轴、保护肠黏膜屏障功能达到治疗NAFLD的目的.

目的 探讨黄芩-黄连治疗溃疡性结肠炎的作用机制.方法 运用中药系统药理学数据库和分析平台(TCMSP)数据库获取黄芩-黄连药对有效成分及预测药物作用靶点;运用在线人类孟德尔遗传数据库(OMIM)数据库及人类基因数据库(GeneCards)获取溃疡性结肠炎疾病基因;得出交集靶标基因后运用STRING探讨其相关性,分析潜在作用机制.结果 共收集到黄芩-黄连药对活性成分41种,活性成分预测靶标基因179个,溃疡性结肠炎的靶标基因411个,药物-疾病交集靶标基因41个,基因本体(GO)功能富集分析表明主要涉及信号传导、细胞增殖等生物过程,京都基因和基因组百科全书(KEGG)富集分析表明黄芩-黄连药对治疗溃疡性结肠炎主要通过癌症通路、TNF通路、IL-17通路及Toll样受体信号通路等发挥作用.结论 黄芩-黄连治疗溃疡性结肠炎是通过多活性成分-多靶点-多通路的复杂过程,或可降低溃疡性结肠炎发展成为结直肠癌的风险.

目的 探讨茵陈苓桂剂对高脂饮食诱导的非酒精性脂肪肝模型大鼠脂代谢及氧化应激的影响.方法 将60只SD大鼠随机分为正常组10只,造模组50只,正常组给予普通饲养,造模组给予高脂饲料.第8周末,造模组随机抽取2只大鼠做肝组织病理切片提示造模成功,将其随机分为多烯磷脂酰胆碱组,以及茵陈苓桂剂高、中、低剂量组,每组10只,剩余为模型组.各给药组给予相应药物灌胃治疗,正常组、模型组给予等体积蒸馏水,干预4周后,HE染色观察肝组织病理并计算非酒精性脂肪肝病活动度积分(NAFLD activity score,NAS),生化法检测血清天门冬氨酸基转移酶(aspartate aminotransferase,AST)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC),ELISA测定血清及肝组织丙二醛(malondialdehyde,MDA)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-PX)、超氧化物歧化酶(super oxide dismutase,SOD)的水平.结果 (1)与正常组比较,模型组大鼠血清ALT、AST、TC、TG水平显著升高(P＜0.01),大鼠血清、肝组织MDA水平均显著升高(P＜0.05或P＜0.01),而SOD、GSH-PX水平降低(P＜0.05或P＜0.01).(2)与模型组比较,西药组与中药高、中剂量组大鼠血清ALT、AST、TC、TG水平均降低,中药低剂量组大鼠血清AST、TC显著降低(P＜0.05或P＜0.01).(3)与模型组比较,西药组与中药中、低剂量组血清、肝组织GSH-PX均升高(P＜0.01),西药组与中药低剂量组血清SOD升高(P＜0.05),而西药组肝组织SOD升高(P＜0.01),中药高剂量组血清、肝组织MDA降低(P＜0.05),GSH-PX及SOD水平升高(P＜0.05或P＜0.01).(4)与西药组比较,中药高剂量组血清、肝组织GSH-PX显著升高(P＜0.01).(5)肝组织病理结果发现:与模型组相比,各给药组肝组织脂肪变、炎细胞浸润、肝小叶结构均有所改善,NAS均降低(P＜0.05或P＜0.01).结论 茵陈苓桂剂可有效调节非酒精性脂肪肝病大鼠的血脂和肝酶,降低大鼠血清、肝组织MDA水平,提高SOD、GSH-PX活性,因此能保护肝功能,调节脂代谢,改善肝脏病理损伤,减少脂质过氧化物的产生,增强抗氧化能力,从而恢复氧化—抗氧化系统平衡,这可能是其防治非酒精性脂肪肝病的作用机制之一.