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.

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.

OBJECTIVE:To explore if Hewei Jiangni granule (, HWJNG) could regulate esophageal hypersensitivity via stromal interaction molecule 1 (STIM1)/transient receptor potential vanilloid subfamily member 1 (TRPV1) pathway. METHODS:Qualitative analysis of HWJNG was analysis by high performance of liquid and gas chromatography. In vivo, animal model of non-erosive reflux disease (NERD) was established by fructose intake and restraint stress. HWJNG and Omeprazole were administered by gavage to the drug intervention group. Reflux and visceral hypersensitivity were analyzed by pathological changes, PH value test, mechanical paw withdrawal threshold, thermal withdrawal latency and mast cells (MCs) degranulation. In vitro, substance P (SP)-induced P815 cells and dorsal root ganglion (DRG) cells were co-cultured. Expression in both mice and cells of STIM1, TRPV1, and esophageal visceral hypersensitivity-related gastrointestinal neurochemicals were validated by enzyme linked immunosorbent assays, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Moreover, overexpression and small interfering RNA against STIM1 were utilized to verify of the role of HWJNG in DRG cells. RESULTS:HWJNG significantly suppressed intercellular space widening, injury of mitochondrial, MCs degranulation, mechanical allodynia and heat neuropathic sensory and increased pH value of esophageal mucosa in NERD mice. HWJNG inhibited expression of visceral hypersensitivity-related gastrointestinal neurochemicals in esophageal mucosa and activated P815 cells, and expression of the STIM1, TRPV1 and related neurotransmitters in DRG and DRG cells. STIM1 siRNA and HWJNG both reduced P815 cells adhesion to DRGs cells and Ca2+ flow into the cytoplasmic space of DRG cells. Furthermore, HWJNG could reversed STIM1 overexpression induced upregulation of TRPV1. CONCLUSION:HWJNG suppressed intercellular space widening in NERD mice, stabilized MCs and restored neuronal hyperexcitability by regulating visceral hypersensitivity viaSTIM1/TRPV1 pathway.

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.

OBJECTIVE:To evaluate the safety and efficacy of Hewei Jiangni recipe (, HWJNR) for treating nonerosive gastroesophageal reflux (NERD) with cold-heat complex syndrome and to clarify its mechanism based on correlation analyses of intestinal flora and metabolites. METHODS:Seventy-two patients with NERD and the Traditional Chinese Medicine (TCM) syndrome of intermingled heat and cold were randomly assigned to either the TCM group or the Western Medicine group, each receiving 8 weeks of treatment. The primary outcome was the score of the gastroesophageal reflux disease questionnaire (GERD-Q). Additionally, 10 healthy individuals were recruited. Mechanistic outcomes included correlation analyses of intestinal flora and metabolites in healthy individuals and NERD participants before and after treatment. RESULTS:After 8 weeks, the effectiveness rate was 90% in the TCM group and 86.67% in the Western Medicine group (P >0.05). Compared with omeprazole, the TCM group significantly improved quality of life and alleviated symptoms such as loss of appetite, fatigue, bowel sounds, and coldness in the hands and feet (P < 0.05). Dysregulation of intestinal flora and metabolic pathways in NERD patients was restored to balance after TCM treatment, which appeared related to the TCM regulation of "cold and heat disorders." CONCLUSION:HWJNR was clinically as effective as omeprazole and demonstrated advantages in improving quality of life.

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.

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.

腹泻型肠易激综合征(Diarrhea-predominant IBS,IBS-D)是一种功能性肠病,其发病机制尚未完全阐明,目前亦缺乏确切有效的治愈方法.近年来大量研究显示,胆汁酸代谢失常可激活G蛋白偶联胆汁酸受体5(G-protein-coupled bile acid receptor 5,TGR5)信号通路的活性,诱导肠嗜铬细胞、肠L细胞、肠巨噬细胞等异常分泌5-羟色胺、降钙素基因相关肽、胰高血糖素样肽-1及炎症因子等,从而导致肠道动力异常、内脏敏感性增加以及肠黏膜低级别炎症等,最终引发IBS-D,因此,胆汁酸代谢-TGR5轴在IBS-D的发生发展中起着重要的调节作用.本文从胆汁酸代谢-TGR5轴入手,总结近年来国内外文献,旨在阐明其调控IBS-D的作用及其机制,并与中医药论治相结合,为IBS-D的治疗提供新的思路.

BackgroundHepatocellular carcinoma (HCC) is a highly invasive disease with a high mortality rate. Our previous study found that Chenodeoxycholic acid (CDCA) as an endogenous metabolite can enhance the anti-tumor effect. Sorafenib has limited overall efficacy as a first-line agent in HCC, and combined with CDCA may improve its efficacy. MethodsHepG2 cells and Balb/c nude mice were used respectively for in vitro and in vivo experiments. Flow cytometry, Western blotting, HE and immunohistochemical staining and immunofluorescence were used to study the effects of CDCA combined with sorafenib on HepG2 cell growth and apoptosis-related proteins. Magnetic bead coupling, protein profiling and magnetic bead immunoprecipitation were used to find the targets of CDCA action. The effect of CDCA on EGFR/Stat3 signaling pathway was further verified by knocking down Stat3 and EGFR. Finally, fluorescence confocal, and molecular docking were used to study the binding site of CDCA to EGFR. ResultsIn this study, we found that CDCA enhanced the effect of sorafenib in inhibiting the proliferation, migration and invasion of HepG2 cells. Magnetic bead immunoprecipitation and protein profiling revealed that CDCA may enhance the effect of sorafenib by affecting the EGFR/Stat3 signaling pathway. Further results from in vitro and in vivo gene knockdown experiments, confocal experiments and molecular docking showed that CDCA enhances the efficacy of sorafenib by binding to the extracellular structural domain of EGFR. ConclusionThis study reveals the mechanism that CDCA enhances the inhibitory effect of sorafenib on HepG2 cell growth in vitro and in vivo, providing a potential new combination strategy for the treatment of HCC.

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].

Purpose: Proton pump inhibitors, as the first-line drugs for treating gastroesophageal reflux disease (GERD), are unable to completely relieve patients??? symptoms and patients are prone to recurrence after prolonged drug withdrawal. Thus, it is crucial to find herbal medicines as a complementary and alternative treatment. Hewei Jiangni granule (HWJNG) is a classical Chinese medicinal formula with clinical therapeutic effects on GERD, but its pharmacological mechanism of action remains unclear. This study aimed to explore and then verify the pharmacological mechanisms of HWJNG in GERD therapy. Methods: A network pharmacology approach was applied to explore and then verify the pharmacological mechanisms of HWJNG in GERD therapy. The active ingredients of HWJNG, as well as therapeutic targets of GERD were acquired from specialized databases. The ???herb-ingredient-gene-target??? network for HWJNG in GERD treatment was built. The protein???protein interaction (PPI) network was constructed to screen the core coincident targets. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. The core targets and signaling pathways associated with the anti-neurogenic inflammatory effect were partially verified via experiments in vivo at molecular level. Results: In total, 179 chemical ingredients in HWJNG and 298 intersection targets between GERD and HWJNG were selected from databases. A large proportion of core targets and top signaling pathways were involved in neurogenic inflammation. HWJNG significantly alleviated pathological injuries of esophagus and reversed dilated intracellular spaces. Additionally, HWJNG markedly inhibited the excessive release of inflammatory cytokines such as interleukin (IL)-1??, IL-6, tumor necrosis factor receptor (TNF-a), as well as regulated stimulation sensors including transient receptor potential vanilloid type 1 (TRPV1) and its related neuroinflammatory mediators in GERD mice. Conclusion: HWJNG is a promising therapeutic strategy for GERD treatment via regulation of multiple targets and pathways, its effects in alleviating neurogenic inflammation are especially acknowledged.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disease characterized by visceral hypersensitivity-related abdominal pain, in which diarrhea-predominant IBS (IBS-D) is the main subtype and has a high clinical incidence. Tongxie Anchang Decoction (TXACD) has been proved to significantly improve abdominal pain in patients with IBS-D, but its underlying therapeutic mechanism still remains unclear. In the present study, IBS-D model rats were induced by neonatal maternal separation (NMS) combined with restraint stress (RS). The therapeutic effect of TXACD was evaluated by fecal characteristics and abdominal withdrawal reflex (AWR) scores. After 14 days of intragastric administration, the colonic tissues of rats were collected to detect the protein and gene level of the NGF, TrkA, and TRPV1 using Western blotting and real-time polymerase chain reaction, respectively, and detect mast cells infiltration using toluidine blue staining. The abdominal aorta blood centrifuged was collected for detecting serum levels of SP, 5-HT, and CGRP with ELISA. The results revealed that TXACD could significantly improve visceral hypersensitivity in IBS-D rats, reflected in the decrease of AWR score and the serum levels of SP, 5-HT, and CGRP. In addition, TXACD treatment could alleviate mast cells infiltration. Moreover, the expression levels of the NGF, TrkA, and TRPV1 were repressed by TXACD. The findings of the present study indicated that the therapeutic effect of TXACD on visceral hypersensitivity might be closely related to the downregulation of the NGF/TrkA signaling pathway, the reversal of TRPV1 expression and mast cells infiltration, and the decreased release of neuroendocrine factors SP, 5-HT, and CGRP.

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.

功能性消化不良(FD)是消化科常见的功能性胃病,其虽无明显器质性病变,但在我国发病率较高,现代医学对其发病机制尚未完全阐明,且临床疗效差.中医药对FD的治疗显示出了明显优势,谢春娥教授认为FD病位在脾胃,与肝密切相关,中焦斡旋失司为其基本病机.在治疗方面善于调升降助纳运以复斡旋,用药强调避滋补,并将消积法贯穿治疗始末,以药力助机体恢复正常的功能,药物结合积极适当的沟通以改善患者的肝郁症状,缩短病程.