ETHNOPHARMACOLOGICAL RELEVANCE:Microbial fermentation is an indispensable processing technology in traditional Chinese medicine (TCM). This technology uses functional microorganisms to transform bioactive components, addressing limitations of TCMs including low solubility of active ingredients, poor bioavailability and potential toxicity. Microbial fermentation preserves TCM's traditional therapeutic effects, integrates modern advantages, and thus bridges traditional TCM knowledge with current healthcare needs. However, inconsistent fermentation outcomes due to strain specificity, potential microbial contamination during scaling, and uncharacterized long-term safety of novel fermented metabolites remain non-negligible risks that require targeted mitigation. AIM OF THE REVIEW:Despite the increasing attention on microbial fermentation in TCM, existing reviews primarily focus on phenomenological descriptions (e.g., component content changes, basic fermentation effects) and lack systematic integration of molecular mechanisms, emerging fermentation strategies, and industrial application guidance, and differentiation of evidence types (in-vitro, in-vivo, human). Notably, the interaction mechanisms between microorganisms and TCM components, as well as standardized processes for fermentation scalability, remain underexplored. To address these gaps, this review updates the latest progress in microbial application in TCM, with a focus on enzyme-mediated component transformation mechanisms, structure-activity relationships of key bioactive substances (polysaccharides, flavonoids, alkaloids), optimization of fermentation processes (strains, methods, parameters), and practical applications in health food, animal husbandry, and medicine. It aims to synthesize scattered research evidence into a cohesive theoretical framework, clarify current technical bottlenecks, and provide targeted references for subsequent mechanistic exploration and industrial translation of fermented TCM. MATERIALS AND METHODS:Information relevant to the Application of Microorganisms in Fermented TCM was collected by searching the scientific databases (Google Scholar, PubMed and International Plant name Index). Botanical plant names were validated using the Plant List (www.theplantlist.org). To ensure the rigor and objectivity of this review, we established explicit inclusion and exclusion criteria for literature screening. INCLUSION CRITERIA:(1) Original research or reviews published in peer-reviewed journals; (2) Studies focusing on microbial fermentation of TCM (including single herbs, compound formulas, and TCM-derived resources); (3) Research involving clear fermentation strains, process parameters, or component-efficacy relationships; (4) Studies providing quantitative data on component changes or pharmacological effects. EXCLUSION CRITERIA:(1) Conference abstracts, unpublished dissertations, or non-peer-reviewed literature; (2) Studies with unclear experimental design or incomplete data; (3) Duplicate publications or secondary analyses of existing datasets; (4) Research unrelated to microbial fermentation (e.g., chemical synthesis or physical processing of TCM). Literature screening was performed by two independent researchers, and eligible studies were cross-validated to ensure reliability. RESULTS:Functional microorganisms drive transformations of TCM components during fermentation. They decompose macromolecules into absorbable small molecules, convert toxic components into low-toxic derivatives, and generate new bioactive compounds. In-vitro studies confirm these component transformations; in-vivo animal models validate enhanced efficacy and reduced toxicity; and preliminary human evidence supports potential clinical applications. These changes enhance TCM efficacy and improve safety. Fermented TCM shows broad application value in health food and medicine. However, microbe-TCM interaction mechanisms remain unclear, standardization is insufficient and microbial resources are underexplored. CONCLUSIONS:Microbial fermentation optimizes TCM quality by enhancing efficacy, reducing toxicity and expanding applications, with a clear link between component changes and improved pharmacology. Future research should use multi-omics to clarify interactions, establish standardized processes and explore novel microbial resources.

Microfluidics enables precise manipulation of scarce Traditional Chinese Medicine (TCM) samples while accelerating analysis and enhancing sensitivity. Device-level structures explain these gains: staggered herringbone and serpentine mixers overcome low-Reynolds-number constraints to shorten diffusion distances and reduce incubation time; flow-focusing or T-junction droplet generators create one-droplet–one-reaction compartments that suppress cross-talk and support high-throughput screening; “Christmas-tree” gradient generators deliver quantitative dosing landscapes for mechanism-aware assays; micropillar/weir arrays and nanostructured capture surfaces raise surface-to-volume ratios and probe density, improving capture efficiency and limits of detection; porous-membrane, perfused organ-on-a-chip architectures recreate apical–basolateral transport and physiological shear, enabling metabolism-aware pharmacology and predictive toxicology; wax-patterned paper microfluidics (µPADs) use capillary networks for instrument-free metering in field settings; and lab-on-a-disc radial channels/valves exploit centrifugal pumping for parallelised workflows. Framed by key performance indicators—sensitivity (LOD/LOQ), reliability/reproducibility, time-to-result, throughput, sample volume, and sustainability/cost—this review synthesises how such structures translate into value across TCM quality/safety control, toxicology, pharmacology, screening, and delivery. Emphasis on structure–function relationships clarifies where microfluidics most effectively closes gaps between chemical fingerprints and biological potency and indicates practical routes for standardisation and deployment.

Inflammatory bowel disease (IBD) is a chronic recurrent IBD, whose cause involves the interaction between genetic and environmental factors. Although there is a recognized link between immune response and IBD, the causal relationship between circulating immune cell counts and IBD remains controversial. This study aimed to elucidate the causal relationship between genetically predicted circulating immune cell counts and IBD. We conducted a bidirectional 2-sample Mendelian randomization (MR) study using aggregated statistics from genome-wide association studies. The causal relationship between 5 circulating leukocytes cells (monocytes, lymphocytes, eosinophils, basophils and neutrophils) counts and IBD, including ulcerative colitis (UC) and Crohn disease (CD) was analyzed. Horizontal pleiotropy test and heterogeneity test were used to ensure the stability of the results. Our findings indicated that monocytes, lymphocytes, eosinophils, and basophils count were not significantly associated with IBD, however, elevated circulating neutrophils count was significantly associated with higher risk of IBD [odds ratio (OR) = 1.0017; 95% confidence interval (CI) = 1.0004–1.003; P = .009] and UC [OR = 2.465; 95% CI = 1.236–4.916; P = .01]. In addition, we also found that IBD [OR: 12.07; 95% CI = 1.909–76.316; P = .008] and CD [OR = 1.014; 95% CI = 1.004–1.023; P = .005] were significantly associated with higher circulating neutrophils count in reverse MR. This MR study provides genetic evidence for the causal relationship between the genetically predicted increase in circulating neutrophils count and the risk of IBD (UC and CD). This finding stresses the need for further exploring physiological functions of neutrophils in order to develop effective strategies against IBD.

Background:Mesalazine preparations serve as first-line therapy for active mild-to-moderate ulcerative colitis(UC),however,not all patients respond to mesalazine.Patients with mesalazine-refractory UC often switch to corticosteroids,immunological therapy,and biological agents,but their use is limited owing to their well-characterised side effects(e.g.osteoporosis and cushingoid feature).Therefore,there is an unmet medical need for novel treatments with a manageable safety profile for patients with mesalazine-refractory UC.New Wumei Pill is a novel and effective herbal prescription for the treatment of UC,and our preliminary study suggested that New Wumei Pill has a significant effect on patients with mesalazine-refractory UC.However,its effectiveness and safety has not been evaluated convincingly. Objectives:This trail aims to evaluate efficacy,safety and mechanisms of New Wumei Pill in the treatment of patients with mesalazine-refractory UC. Methods:This is a prospective,randomized,double-blind control trial,in which 72 patients with mesalazine-refractory mild-to-moderate UC will be randomized in a 1:1 ratio in the treatment and control group.Patients will be screened for eligibility at the outpatient and ward of the Department of Gastroenterology in Dongfang Hospital,Beijing University of Chinese Medicine.72 participants will undergo strict screening to meet the diagnostic criteria of mildly to moderately active UC,with modified Mayo score of 3-10 points.All patients will be administered by mesalazine enteric-coated tablets for 8 weeks,at the same time,the patients in treatment group will receive New Wumei Pill,while patients from control group will be administered by dummy New Wumei Pill. Results:The primary outcomes are clinical efficacy rate and clinical remission rate according to the modified Mayo score.The secondary outcomes are individual symptom score,TCM syndrome score,endoscopic response rate,mucosal healing rate,and quality of life scale score.Finally,biological samples from participants will be preserved to reveal the mechanisms of New Wumei Pill on UC. Conclusions:We hypothesize that the patients with mesalazine-refractory mild-to-moderate UC will benefit from New Wumei Pill.If successful,this trial will provide evidence of traditional Chinese medicine in the treatment of UC,and hold promises for novel options UC patients and policymakers.

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:Diarrhea-predominant irritable bowel syndrome (IBS-D) is characterized by recurrent abdominal pain and chronic diarrhea. T lymphocytes, which play a crucial role in gut inflammation and immune responses, may significantly contribute to the pathophysiology of IBS-D. However, the exact mechanisms by which T lymphocytes affect IBS-D remain unclear. The precise pathways and interactions involved in IBS-D are still to be determined. METHODS:We conducted single-cell RNA sequencing on blood samples from 4 IBS-D patients and 4 healthy controls. Following data preprocessing, we conducted subsequence bioinformatics analysis. Additionally, serum and colon tissue samples from IBS-D rat models were analyzed using ELISA and three-parameter fluorescence to further elucidate the T lymphocytes landscape associated with IBS-D. RESULTS:A total of 45,649 cells were classified into four distinct cell types. Among them, T lymphocytes were further subdivided into 20 unique clusters. Novel markers that were highly expressed in T lymphocytes were identified. Dysregulation of HIF-1α pathway, NF-kappa B pathway, and IL-17 signaling pathway, were observed through trajectory analysis. Additionally, single-cell regulatory network inference and clustering analysis revealed the FOS signaling pathway as a potential therapeutic target for IBS-D. Furthermore, we detected abnormally elevated levels of PLK3 and NFKBIZ in the serum and colon tissues of the IBS-D rat model. Our study mapped the communication atlas of T lymphocytes that may influence the pathophysiology of IBS-D. CONCLUSIONS:This study uncovers novel molecular features and identifies potential therapeutic targets of T lymphocytes in IBS-D, thereby advancing our understanding of the disease and expanding treatment options.

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.

This study explored the effect of plant-derived indigo supplementation on intestinal inflammation using in vivo, in vitro, and clinical sample analyses. Our results showed that indigo decreased mucosal inflammation by regulating CD4+ T cell differentiation in a gut microbiota-dependent manner. Microbes transferred from indigo-treated mice, indigo-induced enrichment of Roseburia intestinalis, and its metabolite butyrate played a role in Th17/Treg immunity similar to that of indigo in intestinal inflammation, which was involved in mTORC1/HIF-1α signal-mediated reprogrammed glucose metabolism. We further showed that patients with ulcerative colitis exhibited significant gut dysbiosis and CD4+ T cell differentiation abnormalities. Our findings provide new insights into the gut-immune axis in ulcerative colitis, offering a novel microbial-based immunotherapy for the treatment of inflammatory bowel disease.

>To the Editors: We read with great interest the study recently published by Sun et al 1 entitled “Electroacupuncture at Tianshu(ST25) and Zusanli(ST36) alleviates stress-induced irritable bowel syndrome in mice by modulating gut microbiota and corticotropin-releasing factor” in which the microbial details of electroacupuncture(EA)-induced protection in irritable bowel syndrome(IBS) were investigated.

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.

Background:Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease that lacks effective treatments. Qingchang Wenzhong Decoction (QCWZD) is a clinically effective herbal prescription that has been proven to attenuate intestinal inflammation in IBD. However, its molecular mechanism of action has not been clearly elucidated. Purpose:We aimed to probe the mechanism of QCWZD for the treatment of IBD. Methods:The dextran sulfate sodium (DSS)-induced mouse model of IBD was used to identify the molecular targets involved in the mechanism of action of QCWZD. Metagenomics sequencing was utilized to analyze the differences in gut microbiota and the functional consequences of these changes. Network pharmacology combined with RNA sequencing (RNA-seq) were employed to predict the molecular targets and mechanism of action of QCWZD, and were validated through in vivo experiments. Results:Our results demonstrated that QCWZD treatment alleviated intestinal inflammation and accelerated intestinal mucosal healing that involved restoration of microbial homeostasis. This hypothesis was supported by the results of bacterial metagenomics sequencing that showed attenuation of gut dysbiosis by QCWZD treatment, especially the depletion of the pathogenic bacterial genus Bacteroides, while increasing the beneficial microorganism Akkermansia muciniphila that led to altered bacterial gene functions, such as metabolic regulation. Network pharmacology and RNA-seq analyses showed that Th17 cell differentiation plays an important role in QCWZD-based treatment of IBD. This was confirmed by in vivo experiments showing a marked decrease in the percentage of CD3+CD4+IL-17+ (Th17) cells. Furthermore, our results also showed that the key factors associated with Th17 cell differentiation (IL-17, NF-κB, TNF-α and IL-6) in the colon were significantly reduced in QCWZD-treated colitis mice. Conclusion:QCWZD exerted beneficial effects in the treatment of IBD by modulating microbial homeostasis while inhibiting Th17 cell differentiation and its associated pathways, providing a novel and promising therapeutic strategy for the treatment of IBD.

Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, is a chronic relapsing gastrointestinal inflammatory disease mediated by dysregulated immune responses to resident intestinal microbiota. Current conventional approaches including aminosalicylates, corticosteroids, immunosuppressive agents, and biological therapies are focused on reducing intestinal inflammation besides inducing and maintaining disease remission, and managing complications. However, these therapies are not curative and are associated with various limitations, such as drug resistance, low responsiveness and adverse events. Recent accumulated evidence has revealed the involvement of mucin-degrading bacterium Akkermansia muciniphila (A. muciniphila) in the regulation of host barrier function and immune response. Although the role of commensal A. muciniphila in IBD is controversial and needs further investigations, most clinical and experimental results still support the protective effect of A. muciniphila in the process and development of intestinal inflammation. Therefore, A. muciniphila-targeted and -based therapies is now considered a valuable therapeutic approach to treat IBD patients. However, how to selectively enrich the growth and colonization of A. muciniphila in the host intestine with direct or indirect interventions have not been clarified. This review reveals an interesting phenomenon that not only viable A. muciniphila, but pasteurised A. muciniphila, and its ingredients such as AmEVs, Amuc_1100 and P9 also can alleviate intestinal inflammation, suggesting a therapeutic potential of A. muciniphila in the treatment of IBD. More importantly, because of the natural characteristics individual strains grow, we believe that it is more promising weapon for the treatment of IBD to improve the intestinal microenvironment of A. muciniphila than to simply increase the number of individual bacteria itself. Therefore, it has become a research hotspot in recent years to improve intestinal microenvironment and indirectly promote the colonization of A. muciniphila through the supplementation of other probiotic or prebiotics, natural diets, drugs, and herbs, and achieved good progress, holds promise for A. muciniphila-targeted and -based therapies in the treatment of IBD.

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.

Inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, is a chronic relapsing gastrointestinal inflammatory disease mediated by dysregulated immune responses to resident intestinal microbiota. Current conventional approaches including aminosalicylates, corticosteroids, immunosuppressive agents, and biological therapies are focused on reducing intestinal inflammation besides inducing and maintaining disease remission, and managing complications. However, these therapies are not curative and are associated with various limitations, such as drug resistance, low responsiveness and adverse events. Recent accumulated evidence has revealed the involvement of mucin-degrading bacterium Akkermansia muciniphila ( A. muciniphila ) in the regulation of host barrier function and immune response, and how reduced intestinal colonisation of probiotic A. muciniphila can contribute to the process and development of inflammatory bowel diseases, suggesting that it may be a potential target and promising strategy for the therapy of inflammatory bowel disease. In this review, we summarise the current knowledge of the role of A. muciniphila in IBD, especially focusing on the related mechanisms, as well as the strategies based on supplementation with A. muciniphila , probiotics and prebiotics, natural diets, drugs, and herbs to promote its colonisation in the gut, and holds promise for A. muciniphila -targeted and -based therapies in the treatment of inflammatory bowel disease.

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.

Objective To explore the effect of rhein on M1/M2 macrophage balance in mice with nonalcoholic steatohepatitis(NASH),providing a theoretical basis for traditional Chinese medicine treatment of NASH.Methods Healthy SPF male C57BL/6 mice were randomly divided into control group,model group,low dose rhein group and high dose rhein group.The model group,the low dose rhein group and the high dose rhein group consumed a high-fat diet ad libitum for 10 weeks to establish the NASH model,and the control group received regular feed.After successful modeling,the low dose rhein group and the high dose rhein group were given the corresponding concentration of drugs by gavage for 4 weeks,while the control group and the model group were given equal amounts of distilled water by gavage.The body weight of mice,morphological and pathological changes in the liver tissue in each group were compared.The levels of M1/M2 macrophages in spleens were determined by flow cytometry.The expression of tumor necrosis factor-α(TNF-α)mRNA and interleukin-10(IL-10)mRNA in liver tissues were determined by quantitative reverse transcription PCR.Results Mice in the model group had significantly higher body weight compared with the control group(P＜0.01).After 4 weeks of drug treatment,weight was decreased in the low dose rhein group compared with the model group(P＜0.05)and was significantly decreased in the high dose rhein group(P＜0.01).The liver of the model group was large and soft,showing a yellow color,with vacuolar degeneration,adipose degeneration,and inflammatory cell infiltration in the liver tissue.The liver morphological and pathological changes in each dose group of rhein were alleviated.In terms of mechanism,compared with the control group,the model group showed a significant increase in the level of F4/80+CD16/32+ macrophages(M1)and their cytokine TNF-α mRNA(P＜0.01),while the level of F4/80+CD206+ macrophages(M2)and their cytokine IL-10 mRNA were slightly increased without statistical difference.After drug intervention,the level of M1 and TNF-α mRNA in each dose group were significantly reduced(P＜0.05),while the level of M2 and IL-10 mRNA were sig-nificantly increased(P＜0.01,P＜0.05).Conclusion Rhein can significantly ameliorate hepatocyte steatosis and inflammatory cell infiltration in NASH mice,and the mechanism of action was related to the restoration of M1/M2 type macrophage balance.

Rationale:Gastric hyperplastic polyp (GHP) commonly arises in the abnormal background mucosa, which makes it easy to be misdiagnosed and missed, and has a potential risk of malignant transformation over time. Here, we present a case of neoplastic transformation of GHP in a context of autoimmune gastritis (AIG). Patient concerns:In 2020, a 67-year-old woman was admitted for endoscopic review 6 years after gastric polyp resection, the histological diagnosis of gastric polyp was neoplastic transformation of GHP as before. The patient had undergone multiple polypectomies at the same part. Then histological examination revealed that partial epithelial hyperplasia and dysplasia, and the neoplastic areas were interlaced with normal mucosa. Diagnoses and interventions:We further found that the background diagnosis was AIG. These results supported the diagnosis of neoplastic transformation of GHP in a context of AIG. With the doubt of missed diagnose, we retrospectively analyzed the medical history in 2014, 2015 and 2016, confirmed the presence of AIG. Unfortunately, serological tests and special treatment were not performed. Outcomes:The correct diagnosis was eventually confirmed in 2020, which enables patients to receive normal treatment and monitoring, and avoids further deterioration of the disease. Lessons:The purpose of this case report is to increase clinical awareness of neoplastic transformation of GHP in a context of AIG, and hope promise for early diagnosis and treatment.