Background Cholestatic liver disease (CLD) is a complex and multifactorial chronic disorder that requires a systematic and integrative management. Evodiamine (EVO), a natural alkaloid derived from Evodiae Fructus, has demonstrated significant therapeutic potential in ameliorating digestive diseases. However, the beneficial effects of EVO on CLD and the underlying mechanisms remain poorly understood. Objective This study aims to elucidate the mechanisms through which EVO modulates the progression of CLD, with a particular focus on the regulation of gut-liver axis homeostasis. Methods The therapeutic efficacy of EVO in bile duct ligation (BDL)- and α-naphthyl isothiocyanate (ANIT)-induced CLD rat models was systematically evaluated. An integrative approach combining network pharmacology with multi-omics analyses (transcriptomic, metagenomic sequencing, targeted bile acid metabolomics) was employed to identify significantly altered molecular networks. Fecal microbiota transplantation (FMT) was conducted to validate the functional role of gut microbiota in the hepato-intestinal protective effects. Direct molecular targets as well as the functional validation were confirmed through molecular docking, pull-down assays, surface plasmon resonance and cellular thermal shift assay. Results EVO achieved significant synchronous hepato-intestine protection in both CLD rats: it markedly ameliorated hepatic injury and hepatic fibrosis, downregulated pro-inflammatory cytokine levels, while preserving intestinal barrier integrity and alleviating intestinal inflammation. Mechanistically, EVO exerted these protective effects by directly targeting the tight junction protein ZO-1 and enhancing its expression and stability. Furthermore, EVO restored intestinal microbial homeostasis, corrected dysregulated BA metabolism-specifically normalizing deoxycholic acid (DCA) levels. FMT experiments demonstrated that the synchronous hepato-intestinal beneficial effects of EVO were partially mediated by gut microbiota. Conclusion EVO exerts a protective effect against CLD by directly targeting ZO-1 to strengthen intestinal barrier function, thereby restoring gut microbial balance and rebalancing BAs metabolism (especially DCA levels) in the gut-liver axis. This study uncovers a novel ZO-1-dependent mechanism of EVO in CLD, highlighting EVO as a promising candidate for the treatment of CLD and providing new insights into gut-liver axis-targeted therapies.

The skin and mucosal barriers serve as essential frontline defenses, protecting against pathogens, environmental insults, and excessive water loss while maintaining physiological homeostasis. Sea buckthorn (Hippophae rhamnoides), a plant long utilized in traditional medicine, has recently garnered scientific attention for its therapeutic potential in enhancing barrier integrity. Modern studies reveal that its bioactive compounds—including flavonoids, unsaturated fatty acids, vitamins, and carotenoids—exert multifaceted pharmacological effects, such as anti-inflammatory, antioxidant, and tissue-repair properties. These mechanisms not only reinforce barrier function but also mitigate inflammation and accelerate healing. This review synthesizes current evidence on sea buckthorn’s multi-target anti-inflammatory actions and its implications for skin and mucosal health through a unique lens of the inflammatory cascade. By elucidating its molecular and cellular effects across distinct stages of inflammation, we provide a foundation for translating these insights into novel dermatological and mucosal therapeutics. The findings underscore the untapped potential of natural products in barrier protection and regenerative medicine, paving the way for future clinical applications.

BACKGROUND:A growing body of clinical evidence points to an association between hypertension and anxiety, but the mechanisms by which the two occur are unclear. This article aims to explore possible common influences and associations between hypertension and anxiety. METHODS:We searched for publications on hypertension and anxiety from January 01, 2004 to December 31, 2022 in Web of Science and performed bibliometrics using CiteSpace, VOSviewer, Scimago Graphica and Gephi. RESULTS:A total of 3216 related articles were retrieved from the Web of Science database. After screening, 3051 articles were included. The number of published articles has increased over the past 19 years. The United States has more researches in this area and has strong collaborative relationships with other countries, which gives it some credibility and authority. The words that appear in the burst keywords are gender, age, obesity, depression, panic disorder, pregnancy induced hypertension, coronary heart disease, chronic kidney disease, and pituitary adrenal axi, which are co-related with hypertension and anxiety. CONCLUSION:There is a link between hypertension and anxiety, and the 2 influence each other, usually in a positive way. Common influences on hypertension and anxiety include age, gender, obesity, depression, panic attacks, pregnancy, coronary heart disease and chronic kidney disease. Recent research hotspots have focused on population aging and comorbidities. Future research hotspots are likely continue to focus on influencing factors, clinical research and prognosis.

Background The traditional Chinese medicine Phytolacca acinosa Roxb (PAR), known as Shanglu, possesses recognized therapeutic benefits against many diseases. PAR is also hepatotoxic, making it a major public health problem. However, the specific toxic substances and molecular mechanisms of PAR remain unclear. Therefore, appropriate animal models and methods are essential to confirm the toxic components and related mechanisms of PAR. Methods L-02 cells and zebrafish larvae at 4 days post-fertilization (4 dpf) were used as models and treated with various concentrations of phytolaccagenin (Phy), esculentoside A (EsA), and esculentoside H (EsH). The hepatotoxicity of three samples was assessed based on liver phenotype, pathological assessments, and biochemical index in zebrafish and proliferative activity, apoptosis level, and biochemical index in L02 cells. The transcriptomic technique was used to explore the related signaling pathways and potential mechanisms in vitro and in zebrafish , and the findings were validated by RT-PCR. Results The results of acute toxicity tests indicated that Phy exhibited substantially more severe hepatotoxicity than EsA, while EsH did not lead to any obvious toxic effects. Especially, under sublethal exposure (<LC10), both Phy and EsA induced similar liver damage in zebrafish and L-02 cells, increasing mortality, disrupting morphology, enhancing apoptosis, altering liver enzyme levels, and leading to significant structural changes in cells and zebrafish. Multiomics analysis of 605 genes in L-02 cells and 780 genes in zebrafish showed that exposure to Phy significantly altered gene expression in various biological processes. Further enrichment analysis demonstrated that Phy predominantly affects the P53\apoptosis\cell cycle arrest, ferroptosis, PPAR signaling, and arachidonic acid metabolism, leading to notable cellular damage. Conclusion This study identified Phy as a key hepatotoxic component of PAR. Furthermore, using transcriptomic techniques, we preliminarily investigated the hepatotoxic mechanisms of Phy in vitro and in vivo. The results of the present study showed that Phy affects several signaling pathways, including those involved in lipid metabolism, oxidative stress, and apoptosis, finally leading to hepatotoxicity. These findings provide invaluable insights into the safe use of PAR in clinical settings.

BACKGROUND:Venenum Bufonis (VB), a traditional Chinese medicine (TCM), is renowned for its therapeutic detoxification, pain relief, and cognitive enhancement effects. VB has been classified as a toxic TCM in medical literature, and its clinical usage is currently subject to several limitations. However, the toxicological characteristics of VB and underlying mechanisms remain unclear. METHODS:We conducted a comprehensive assessment to confirm the target organs affected by VB using the zebrafish model. Subsequently, network pharmacology, transcriptomic and proteomic analyses were performed to explore the associated mechanisms, with the aim of providing a basis for its clinical application. RESULTS:VB exhibited dose-dependent toxic effects on zebrafish, particularly causing gross morphological abnormalities in the liver along with aggravated hepatocyte apoptosis. Pericardial edema and an enlarged atrioventricular septum were also observed. The combined analyses revealed significant alterations induced by VB in gene expression enriched in multiple pathways and biological processes. Importantly, TLR4/RIPK2/NF-κB and Wnt signaling-mediated inflammation, fibrosis, and apoptosis were identified as the key functional signaling pathways underlying VB-mediated liver toxicity. CONCLUSION:Our results present robust and direct evidence of the hepatotoxic effects induced by VB in zebrafish, while also providing novel insights into the molecular pathways involved. These results establish a solid theoretical foundation for the appropriate clinical application of VB.

Atopic dermatitis (AD) is a chronic relapsing disease with complex pathogenesis. Among them, inflammation is one of the primary pathogenesis of AD. AD is characterized by infiltration of lymphocytes into the skin’s dermis, and the skin homing of lymphocytes plays an essential role in the recurrence of AD. Currently, there is more and more evidence to support this view. This article reviews the relevant role of T lymphocyte skin-homing-related molecules in the recurrence of AD to provide a reference for the cure of AD.

BackgroundThe nod-like receptor family pyrin domain-containing 3 (NLRP3) has been implicated in various skin diseases. However, its role in mediating 2, 4-dinitrofluorobenzene (DNFB)-induced chronic itch remains unclear.MethodsWidetype (WT) and Nlrp3 deletion (Nlrp3-/-)mice, the expression of transient receptor potential (TRP) ankyrin 1 (TRPA1) inhibitor or recombinant mice interleukin-18 (IL-18) were used to establish and evaluate the severity of DNFB-mediated chronic itch. Quantitative real-time PCR, western blotting, immunohistochemistry staining, immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA) was used to examine the expression of NLRP3 inflammasome, type 2 immunity and receptors in dorsal root ganglion (DRG) neurons related with chronic itch. Flow cytometry was performed to quantify the frequency of type 2 immune cells.ResultsThis study revealed that the NLRP3 inflammasome was activated in the skin of DNFB-induced chronic itch mice. Surprisingly, the absence of Nlrp3 exacerbated itch behavior. In Nlrp3-/- mice, IL-18 expression was downregulated, whereas markers of type 2 immunity, such as IL-4 and thymic stromal lymphopoietin (TSLP), were significantly upregulated in the skin. Furthermore, TRPA1 and its colocalization with the IL-4 receptor were increased in the DRG. Inhibition of TRPA1 or administration of recombinant IL-18 significantly reduced DNFB-induced itch behavior in Nlrp3-/- mice. Recombinant IL-18 also decreased the expression of TRPA1, IL-4, and TSLP.DiscussionThese findings suggested that the absence of Nlrp3 aggravated DNFB-induced chronic itch by exacerbating type 2 immunity in the skin and enhancing the IL-4/TSLP-TRPA1 axis, potentially driven by reduced IL-18 levels.

Primary cilia (PC) are essential signaling hubs for proper epithelial formation and the maintenance of skin homeostasis. Found on most cells in the human body, including skin cells, PC facilitate signal transduction that allows ciliated cells to interact with the immune system via multiple pathways, helping to maintain immune system homeostasis. PC can be altered by various microenvironmental stimuli to develop corresponding regulatory functions. Both PC and ciliary signaling pathways have been shown to be involved in the immune processes of various skin lesions. However, the mechanisms by which PC regulate cellular functions and maintain immune homeostasis in tissues are highly complex, and our understanding of them in the skin remains limited. In this paper, we discuss key ciliary signaling pathways and ciliated cells in the skin, with a focus on their immunomodulatory functions. We have compiled evidence from various cells, tissues and disease models to help explore the potential immunomodulatory effects of PC in the skin and their molecular mechanisms.

In recent years, spatial transcriptomics (ST) research has become a popular field of study and has shown great potential in medicine. However, there are few bibliometric analyses in this field. Thus, in this study, we aimed to find and analyze the frontiers and trends of this medical research field based on the available literature. A computerized search was applied to the WoSCC (Web of Science Core Collection) Database for literature published from 2006 to 2023. Complete records of all literature and cited references were extracted and screened. The bibliometric analysis and visualization were performed using CiteSpace, VOSviewer, Bibliometrix R Package software, and Scimago Graphica. A total of 1467 papers and reviews were included. The analysis revealed that the ST publication and citation results have shown a rapid upward trend over the last 3 years. Nature Communications and Nature were the most productive and most co-cited journals, respectively. In the comprehensive global collaborative network, the United States is the country with the most organizations and publications, followed closely by China and the United Kingdom. The author Joakim Lundeberg published the most cited paper, while Patrik L. Ståhl ranked first among co-cited authors. The hot topics in ST are tissue recognition, cancer, heterogeneity, immunotherapy, differentiation, and models. ST technologies have greatly contributed to in-depth research in medical fields such as oncology and neuroscience, opening up new possibilities for the diagnosis and treatment of diseases. Moreover, artificial intelligence and big data drive additional development in ST fields. Spatial transcriptomics (ST) technologies and application prospects. (1) Imaging-based approaches, including in situ sequencing (ISS)—where transcripts are amplified and sequenced in tissue—and ISH-based approaches—where imaging probes are sequentially hybridized in tissue. (2) NGS-based techniques, in which positional information is encoded onto transcripts prior to NGS sequencing.

Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting tens of millions of people globally. The causal relationship between metabolites and AD pathology has not yet been formally indicated, and the mediating mechanism by which metabolites affect AD has not yet been explored. This study aimed to determine the genetic relationship between metabolites and AD and to determine the pathways through which amino acid metabolites affect AD. Meta-analysis integrates the results of multiple GWAS analyses using METAL software. Using bidirectional two-sample Mendelian randomization (MR), we analyzed the causal relationships between metabolites and AD. The principal MR test of causal effects was conducted using inverse-variance weighted regression, and we used reverse MR analysis to exclude reverse causality. We also performed the MR-PRESSO test to detect and correct for possible pleiotropic effects, and used the Cochran Q test to assess heterogeneity. Two-step MR was utilized to analyze the mediating factors between amino acid metabolites and the onset of AD. The correlation between mediating factors (inflammatory protein S100A12) and immune cell infiltration was analyzed using the edgeR and GSVA software packages. Using single-cell sequencing data from skin tissues of patients with AD, we studied the regulatory role of the S100A12 gene in immune cells. Multiple drug databases and macromolecular docking were used to search for S100A12-targeting drugs. Bidirectional two-sample MR analyses indicated that twenty-two metabolites and one inflammatory protein (S100A12) were significantly associated with AD pathogenesis. S100A12 is a mediator of amino acid metabolites (N6-methyllysine; N2-acetyl,N6,N6-dimethyllysine and N6,N6-dimethyllysine) that are genetically associated with AD. S100A12 was positively correlated with the infiltration of multiple immune cell types in lesional AD skin. The amino acid metabolites N6-methyllysine; N2-acetyl,N6,N6-dimethyllysine and N6,N6-dimethyllysine influence AD pathogenesis by mediating S100A12 expression.

Ethnopharmacological relevance: Mahuang-Lianqiao-Chixiaodou decoction (MLCD) is a traditional Chinese medicinal (TCM) formula recorded in the Treatise on Febrile Diseases. It is commonly used for clinical treatment of atopic dermatitis (AD). However, the potential mechanisms of MLCD intervention in AD combined with mental disorders behaviors such as anxiety and depression remain elusive and deserves further investigation.Aim of the study: The study aims to observe the effect of MLCD on anxiety-and depression-like behaviors in AD mice and explore the possible neuroinflammatory mechanism of NOD-like receptor 3 (NLRP3) inflammasome.Materials and methods: The chemical components of MLCD extracts were identified using UHPLC-MS. The AD mice were induced by 2,4-dinitrofluorobenzene and treated with MLCD or mometasone furoate (MF, as a positive control) for 7 days. The pathological changes in their skin tissue and brain hippocampus were observed by hematoxylin-eosin staining. Elevated plus-maze test (EPM), open field test (OFT), and the suspended tail (TST) were used to measure the anxiety-and depressive-like behaviors in AD mice. Expression of NLRP3 inflammasome-related proteins in brain hippocampus were measured by the quantitative real-time polymerase chain reaction (qPCR) and western blotting (WB).Results: We found that MLCD contain many active ingredients, including ephedrine, Forsythoside A, phillyrin, glycyrrhizic acid, etc. Both MLCD and MF alleviated skin lesions and promoted positive histopathological changes in the hippocampus of AD mince to varying degrees. MLCD however, could further increase their proportion of open arm entry times (Oentries%) in EPM, residence time in the central area (Ctime) and the proportion of the number of times in the central area (Centries%) in OFT significantly. MLCD also reduces their immobility time in TST considerably. Mechanistically, MLCD downregulated the relative mRNA expression and protein level of NLRP3, Caspase-1, IL-1 beta, and IL-18 in hippocampal tissue compared to the model group.Conclusions: MLCD can alleviate anxiety-like and depression-like behaviors in AD mice by intervening in the gene and protein expression of NLRP3 inflammasome-related factors, thus treating AD.

Ethnopharmacological relevance: Shuyu decoction (SYD), an effective traditional Chinese medicine (TCM), has been widely used for treating deficiency-related diseases for thousands of years. Meanwhile, exercise-induced fatigue (EF), a common physiological phenomenon observed in physical training, has been treated as a deficient condition in TCM for decades. Currently, not many studies have been conducted on the effect of SYD on EF and little is known about its underlying pharmacological mechanism.Aim of the study: This current study was designed to assess the anti-fatigue roles of SYD and explore its effect on exercise-induced immune dysfunction.Materials and methods: Eighteen rats were randomly divided into three groups: normal control (NC) group, model (M) group, and SYD group (27.8 g/kg). The M and SYD group were given treadmill training for 6 weeks. From the fourth week, the SYD group was administered SYD intragastrically for 3 consecutive weeks. After three weeks of treatment, the rats were anesthetized, and the blood and spleen tissue samples were dissected. The blood sample was devoted to the blood biochemical-related indicators, which were used to evaluate the anti-fatigue of SYD. The expression of Interleukin (IL)-6, IL-18, tumor necrosis factor-alpha (TNF-alpha), IL -17, CD3(+), and CD4(+) were detected by ELISA and the level of CD8+ of blood was measured through Flow Cytometry (FC). The histopathological changes of spleen tissue samples were determined by Hematoxylin and eosin (H&E) staining and an estimation of CD3(+), CD4(+), and CD8(+) expression of spleen tissues were calculated through FC.Results: Compared with the M group, the SYD group observed an increase in tensile force and the ratio of cortisol to testosterone (TTE/COR), whereas a reduction in the levels of lactic acid (LAC), blood urea nitrogen (BUN), creatine kinase (CK), (P < 0.01 or P < 0.05). ELISA experiments showed that SYD reduced the expressions of IL-6, IL-18, and TNF-alpha, IL-17 and increased the expression of IL-10 (P < 0.01 or P < 0.05). In the HE test, SYD treatment transformed the structure of the spleen. FC experiments further showed that SYD increased the expressions of CD3(+), CD4(+), and CD8(+) in blood and spleen tissues (P < 0.01 or P < 0.05).Conclusion: Our findings indicate that SYD can alleviate EF by improving inflammation and immunity. However, the relationship between inflammatory factors and the related immune response remains to be further investigated.

Primary cilia (PC) are non-motile and microtube-based organelles protruding from the surface of almost all thyroid follicle cells. They maintain homeostasis in thyrocytes and loss of PC can result in diverse thyroid diseases. The dysfunction of structure and function of PC are found in many patients with common thyroid diseases. The alterations are associated with the cause, development, and recovery of the diseases and are regulated by PC-mediated signals. Restoring normal PC structure and function in thyrocytes is a promising therapeutic strategy to treat thyroid diseases. This review explores the function of PC in normal thyroid glands. It summarizes the pathology caused by PC alterations in thyroid cancer (TC), autoimmune thyroid diseases (AITD), hypothyroidism, and thyroid nodules (TN) to provide comprehensive references for further study.

Objective: To observe the effects of Danggui Shaoyao powder (DSP) on hepatic lipid metabolism and further explore its mechanism of action by peroxisome proliferator-activated receptor (PPARγ)-liver X receptor (LXRα)-adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) pathway regulation. Methods: Eight C57BL/6J male mice were selected as the control group, and 24 ApoE−/− male mice were randomly divided into the atherosclerosis model (AS) group, atorvastatin calcium (AC) group, and DSP group (n = 8 each group). To establish an AS model, ApoE−/− mice were fed a high-fat diet for 16 weeks. Pathologic changes in the aortic vasculature and liver were identified using Oil Red O staining. Triglyceride (TG), cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were determined in the livers using a single-reagent GPO-PAP method. Fluorescence quantitative polymerase chain reaction and western blot were used to observe and evaluate the mRNA and protein expression of the PPARγ-LXRα-ABCA1 intermediates in the liver. Results: After 16 weeks of a high-fat diet, ApoE−/− mice showed more Oil Red O staining in the aorta and liver compared to the CONT group. Compared to the AS group, the DSP and AC treatment reduced aortic plaque and hepatic lipid deposition to varying degrees. Furthermore, DSP significantly reduced the hepatic lipid area in ApoE−/− mice (P < .001) and decreased the levels of TG, TC, and LDL-C in liver (P < .001, P = .027, P < .001, respectively). DSP also significantly increased the levels of PPARγ, LXRα, ABCA1, and ABCG1 mRNA expression, as well as the PPARγ, LXRα, ABCA1, and ABCG1 protein expression in liver. Conclusion: DSP improved hepatic lipid metabolism via PPARγ-LXRα-ABCA1 pathway modulation for AS treatment.

Background: Sodium ferulate (SF), a derivative of ferulic acid, is one of the active constituents in medicinal plants thought to be useful in fighting cardiovascular diseases. However, there still lacks a systematic review of the efficacy and safety of SF in treating coronary heart disease (CHD). It is therefore the purpose of this study to comprehensively review all clinical randomized controlled trials (RCTs) of SF in CHD to assess its efficacy and safety. Methods: All analysis is based on 8 databases as of February 2023, which includes 35 outcomes of RCTs that investigate the effect of SF combination therapy in CHD. The present study evaluates the quality and bias of selected literature by the Jadad scale and Cochrane Collaboration's tools, and also the quality of evidence by GRADE Profiler. Furthermore, it applies sensitivity analysis to assess the high heterogeneity impact of outcomes and conducted subgroup analysis to estimate the influence factors in these studies. The study protocol was set documented, and published beforehand in PROSPERO (Registration No.CRD42022348841). Results: The meta-analysis of 36 studies (with 3207 patients) shows that SF combined with conventional drugs has improved clinical effectiveness for patients with CHD [RR: 1.21 (95% CI 1.17,1.26); p < 0.00001]. Statistically significant results of meta-analyses are also seen in electrocardiography (ECG) efficacy, frequency of angina attacks, endothelium-dependent flow-mediated vasodilation (FMD), nitric oxide (NO), endothelin (ET), whole Blood low shear rate (LS), platelet aggregation test (PAgT), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL6), triglyceride (TG). Adverse events are reported in 6 RCTs. By GRADE approaches, 2 outcomes (clinical efficacy, CRP) indicate a moderate quality of evidence, 17 outcomes indicate low quality of evidence, with the other 16 very low-quality. Conclusion: SF combination therapy has a better curative effect than conventional therapy. However, due to items with low-quality evidence demonstrated in the study, the presence of clinical heterogeneity, and imprecision in partial outcome measures, all these led to limitations in the evidence of this study. Thus, the conclusion needs to be further verified by more in-depth research.

To identify the active constituents, core targets, immunomodulatory functions and potential mechanisms of Dizhi pill (DZP) in the treatment of myopia. The active constituents and drug targets of DZP were searched in the TCMSP, Herb databases and correlational studies. The targets of myopia were searched in the TTD, Genecards, OMIM and Drugbank databases. Gene expression profile data of GSE136701 were downloaded from the GEO database and subjected to WGCNA and DEG analysis to screen for significant modules and targets of myopia. Intersectional targets of myopia and DZP and core targets of myopia were analyzed through the String database. The GO and KEGG enrichment analyses of the interested targets were conducted. Cibersort algorithm was used for immune infiltration analysis to investigate the immunomodulatory functions of DZP on myopia. Autodock was used to dock the important targets and active constituents. Eight targets (STAT3, PIK3CA, PIK3R1, MAPK1, MAPK3, HSP90AA1, MIP, and LGSN) and 5 active constituents (Quercetin, Beta-sitosterol, Diincarvilone A, Ferulic acid methyl ester, and Naringenin) were identified from DZP. In pathways identified by the GO and KEGG enrichment analyses, "ATP metabolic process" and "AGE-RAGE diabetes complication signaling" pathways were closely related to the mechanisms of DZP in the treatment of myopia. Molecular docking showed that both the intersectional targets and core targets of myopia could bind stably and spontaneously with the active constituents of DZP. This study suggested that the mechanisms of DZP in the treatment of myopia were related to active constituents: Quercetin, Beta-sitosterol, Diincarvilone A, Ferulic acid methyl ester and Naringenin, intersectional targets: STAT3, PIK3CA, PIK3R1, MAPK1, MAPK3, and HSP90AA1, core targets of myopia: MIP and LGSN, AGE-RAGE signaling pathway, positive regulation of ATP metabolic process pathway and immunomodulatory functions.

Objective: To explore the mechanism of Huatan Sanjie Fang（HTSJ） in regulating goiter in Graves’ disease（GD） mice by detecting key factors of the Hippo signaling pathway.Methods: A mouse model of GD was established by injecting Ad-TSHR289 adenovirus into the bilateral quadriceps femoris of female mice. Successful mouse models were then randomly divided into a model group, methimazole（MMI） group, and HTSJ group, and fed with deionized water, MMI（4.5 mg/kg per day）, and HTSJ（35.10 g/kg per day）, respectively, for 10 weeks. Histopathological changes of the thyroid gland were subsequently observed by hematoxylin-eosin staining. Radioimmunoassay was used to detect serum total thyroxine（T4） and thyrotrophin-receptor antibody（TRAb） levels. The relative expression of mRNA of Mst1, YAP, and TAZ were detected by quantitative real-time polymerase chain reaction, while the protein expression of Mst1, YAP, TAZ, pMst1, and pYAP were detected by western blot.Results: After 10 weeks of drug intervention, goiter and other pathological changes in the HTSJ group significantly improved compared with the model group, and the levels of serum T4 and TRAb significantly decreased（P =.002, P ＜.001, respectively）. Decreased mRNA expression of Mst1, YAP, and TAZ, the key factors of the Hippo signaling transduction pathway, was also observed（P =.002, P =.022, P ＜.001,respectively）. In contrast, protein expression of Mst1（P =.046）, pMst1（P =.026）, and p YAP（P =.004）increased, while protein expression of YAP and TAZ decreased（P =.041, P ＜.001, respectively）.Conclusion: HTSJ can effectively improve goiter in GD mice through the Hippo signaling pathway.

"阴阳毒"首见于《金匮要略》,历代医家对其争议不断.关于"阴阳",有寒热说、经脉说、隐著说、气血说等说法;关于"毒",有天行异毒、内生毒邪、虫毒等说法.结合《黄帝内经》"阴病发于骨,阳病发于血"理论,阴阳毒可解释为"阳毒在血,阴毒在髓",即阳毒归属血分,阴毒归属髓分.阳毒病机为血热妄行,兼有瘀滞;阴毒为伏毒化热所致.