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.

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.

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 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.

沈金鳌是清代著名医家,其代表作《杂病源流犀烛》设咳嗽专篇,汇诸家之言法古而创新.本文总结了沈金鳌对于咳嗽病因病机、临证辨治、选方用药的认识以及咳嗽病脉等.在病因病机上,外感咳嗽以风、寒、暑热、湿邪为主,强调湿邪,内伤咳嗽重视肺脾肾的联系.在治疗上,首以顺气消痰为要法,辛温散表,甘润养内.新咳实则泻之,久咳以虚为主从气血从论治,分别以补中益气汤及四物汤加减,以郁为主从火从痰论治,重视桔梗的使用.治疗五脏咳选用归经药,治疗六腑咳选引上引下药使得升降相应.协调肺脾肾,重视补水培土以养金.细分发病时间,选方多用二陈汤加减.同时重视脉诊,并创造性地使导引运功与药物治疗相辅相成.

溃疡性结肠炎(UC)的发病机制尚不明确,目前普遍考虑为遗传易感背景条件下环境因素、微生物及其代谢失调等引起的机体免疫紊乱所致.色氨酸作为哺乳动物必需的氨基酸,可通过不同的代谢途径对肠道屏障功能、黏膜免疫细胞、肠道微生物群等产生调控作用,从而参与UC的发生、发展.因此,调节色氨酸代谢途径或代谢产物可能成为未来治疗UC的新策略.本文将对溃疡性结肠炎中的色氨酸代谢及作用机制的研究进展进行综述,以期为其临床诊疗提供新的思路和方法.

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.

Abstract Background: Gastric hyperplastic polyp commonly arises in the abnormal background mucosa, including autoimmune gastritis, also known as type A gastritis. There are no obvious clinical symptoms in the early stages of the disease, which makes it easy to be misdiagnosed and missed, and has a potential risk of malignant transformation over time.Case presentation: In 2020, a 67-year-old woman was admitted for review 6 years after gastric adenoma resection. Upper endoscopy revealed multiple lobulated polyps in the gastric body, which was histologically diagnosed as gastric adenomatous polyp as before. Interestingly, we discovered that the patient had undergone multiple polypectomies at the same part, which was inconsistent with the pathogenesis of adenomatous polyp. Then we did histological examination and revealed that partial epithelial hyperplasia and dysplasia, and the neoplastic areas were interlaced with normal mucosa. We further found that the background diagnosis was autoimmune gastritis. These results supported the diagnosis of neoplastic transformation of gastric hyperplastic polyp, not gastric adenomatous polyp. With the doubt of possible be misdiagnosed, we reviewed the medical history. Retrospective analysis in 2014, 2015 and 2016 confirmed the presence of autoimmune gastritis. Unfortunately, serological tests were not performed and no special treatment was done. Fortunately, the correct diagnosis was eventually confirmed as neoplastic transformation of gastric hyperplastic polyp in a context of autoimmune gastritis in 2020, which enables patients to receive normal treatment and monitoring, and avoids further deterioration of the disease. Conclusions: The purpose of this case report is to increase clinical awareness of neoplastic transformation of gastric hyperplastic polyp in a context of autoimmune gastritis, and hope promise for early diagnosis and treatment.

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.

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).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.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.The correct diagnosis was eventually confirmed in 2020, which enables patients to receive normal treatment and monitoring, and avoids further deterioration of the disease.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.

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.

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.