BACKGROUND AND PURPOSE:Haizao Yuhu Decoction (HYD) is a classic Traditional Chinese Medicine for goiter, but its mechanism related to the "gut-thyroid axis" remains unknown. This study investigates whether HYD treats goiter via this axis and elucidates the underlying mechanisms. METHODS:A rat goiter model was induced with propylthiouracil (PTU), followed by two weeks of HYD treatment. Gut microbiota was analyzed by metagenomic sequencing; fecal and serum short-chain fatty acids (SCFAs) were quantified by targeted LC-MS/MS analysis. Thyroid function was assessed via iodine content and hormone levels. Key proteins in hormone synthesis and apoptosis were evaluated by Western blot and immunohistochemistry. Fecal microbiota transplantation (FMT) supported microbiota causality. RESULTS:HYD alleviated goiter and hypothyroidism. It restored gut microbiota diversity and enriched SCFA-producing bacteria (e.g., Bifidobacterium pseudolongum), coincident with increased SCFAs including butyrate. These SCFA changes correlated with reduced HDAC1/2/3/8 in thyroid tissue, consistent with enhanced histone acetylation, and were accompanied by upregulation of NIS, TG, TPO, and DUOX2. Concurrently, elevated SCFAs were associated with AKT/Mdm2 pathway inhibition, p53 stabilization, downstream activation of P21 and Caspase-3, and suppression of Bcl-2, supporting a model of promoted thyroid cell apoptosis. FMT supported that HYD-modulated microbiota alone reproduced these effects. CONCLUSION:HYD alleviates PTU-induced goiter in rats in a manner associated with gut microbiota remodeling and increased SCFA production, which correlate with enhanced thyroid hormone synthesis and restored apoptosis-a relationship supported by FMT experiments. However, direct interactions between HYD and PTU cannot be fully excluded. These findings are consistent with a model in which HYD acts through the gut-thyroid axis, providing mechanistic insights into its therapeutic effects.

Haizao Yuhu Decoction (HYD), a classic Traditional Chinese Medicine (TCM) formula, is used to treat Yingbing, which corresponds to goiter in modern medicine. Although HYD has been extensively studied for goiter, its specific active components and the underlying mechanisms of action remain to be fully elucidated. This study investigated the effects and mechanisms of HYD in goiter using untargeted LC-MS metabolomics (comparing HYD decoction and HYD-containing serum), network pharmacology for target prediction, and in vitro validation with a TSHR human monoclonal antibody M22 (TSHR hMAb M22)-induced thyroid cell proliferation model, followed by Western blotting to verify key pathway proteins. The comparison of metabolomic profiles between HYD decoction and HYD-containing serum revealed that 2091 metabolites (90.05%) were downregulated, while 231 were upregulated in medicated serum. Network pharmacology predicted targets including AKT1, PIK3CA, ESR2, ESR1, and TP53. HYD-containing serum exhibited pro-apoptotic effects on the cell proliferation model. The underlying mechanism may primarily involve the upregulation of the p53/PUMA/p21 pathway, which subsequently affects caspase-3 activity. Furthermore, the action of HYD may involve non-p53 multiple signaling pathways. HYD may exert its effects by modulating multiple signaling pathways, including p53/PUMA/p21, leading to apoptosis in thyroid cells.

The combination of Euphorbia kansui Liou ex S.B.Ho (kansui) and Glycyrrhiza uralensis Fisch (liquorice) is contraindicated in Chinese medicine, but whether it can be used in clinical practice remains controversial. The classic formula, Gansui Banxia decoction (GBD), contains kansui and liquorice, which is effective in treating an abnormal accumulation of body fluids, such as malignant ascites (MA); however, the contraindications of kansui and liquorice have limited its clinical application. This study aims to provide a theoretical basis for the rational application of kansui-liquorice by investigating its role and mechanism in GBD. LC-MS/MS was used to detect the metabolic differences of - glycyrrhetinic acid, glycyrrhizic acid, glycyrrhizin, glycyrrhizin, glycyrrhizin terpinolipid A, and paeoniflorin - in the liquid of MA rats before and after taking GBD. Network pharmacology was employed to predict the potential targets and mechanisms of GBD in the treatment of MA. The experimental validation was still using MA rats as a model. Flow cytometry was used to assess the expression of immune cells in blood and ascites, and the proliferation and development of T cells in bone marrow and thymus. Elisa was used to detect the content of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in blood. Western blot and qRT-PCR were used to detect the expression of NPs/NPR-A/cGMP/PKG II pathway-related gene and proteins in kidney. The MA model was established by intraperitoneal injection of walker-256 cells at a concentration of 2 × 106/mL and an injection volume of 1 mL. The model was successfully established when the abdominal cavity was obviously distend and touched with a water-shaking sound, and ascites could be seen after opening the abdominal cavity. We confirmed that GBD containing kansui-liquorice could promote the metabolism of liquorice and reduce the precipitation of toxic substances (kansuinine A). It may also target cellular immunity to exert a drug effect. Further experimental verification found that GBD containing kansui-liquorice could promote the activation of the NPs/NPRs/cGMP/PKGⅡ pathway and exert a diuretic effect in MA rats. Besides that, it could increase the proportion of CD8CD28 T cells, reduce the proportion of immune-suppressing cells, and maintain the stability of the developmental environment of the T cells. We believe that kansui and liquorice are important components of GBD, and their combination could promote GBD to promote the clinical remission of MA through direct (activation of the NPs/NPRs/cGMP/PKGⅡ pathway) and indirect (regulating T-cell immunity) water-expelling effects.

Ethnopharmacological relevance: Xiao'er Feike Granules (XFG), containing eighteen incompatibilities, is an approved and widely used classical Chinese medicine prescription for the treatment of pediatric respiratory diseases. Extensive clinical studies have reported that XFG demonstrates high efficacy and minimal adverse reactions in treating acute bronchitis (AB). However, there is an urgent need for a more cohesive evaluation of the evidence regarding the safe clinical use of XFG for AB. A clearer and more systematic summary of relevant randomized controlled trials (RCTs) is necessary to assess the overall efficacy and safety of XFG. Aim of the study: To assess the efficacy and safety of XFG for oral administration in treating AB. Materials and methods: RCTs comparing XFG (experimental group) with traditional Western medicine (TWM, control group) for the treatment of AB were collected by searching three English databases and four Chinese databases up to December 31, 2023. A meta-analysis was conducted by using RevMan 5.4 software, and potential publication bias was assessed by using Stata 12.0. A Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence profile was constructed to evaluate the certainty of the evidence. Results: A total of 2482 children were enrolled in 20 RCTs. The results of the meta-analysis indicated that XFG in combation with TWM is more effective than TWM alone in reducing the disappearance time of cough [MD = -1.92 days, 95% CI (-2.36, -1.47), I-2 = 97%, P < 0.00001, very low certainty], fever [MD = -1.68 days, 95% CI (-2.21, -1.14), I-2 = 99%, P < 0.00001, low certainty], wheezing [MD = -1.82 days, 95% CI (-2.01, -1.63), I-2 = 0%, P < 0.00001, low certainty], lung rales [MD = -1.68 days, 95% CI (-2.04, -1.31), I-2 = 94%, P < 0.00001, very low certainty], expectoration [MD = -1.45 days, 95% CI (-2.27, -0.63), I-2 = 98%, P = 0.0005 < 0.001, very low certainty], and phlegm sounds [MD = -0.92 days, 95% CI (-1.10, -0.74), I-2 = 38%, P < 0.00001, low certainty]. Additionally, shorter cure time [MD = -2.71 days, 95% CI (-3.32, -2.11), I-2 = 84%, P < 0.00001, very low certainty] and the time of antibiotics use [MD = -2.81 days, 95% CI (-3.09, -2.53), I-2 = 37%, P < 0.00001, low certainty], lower levels of inflammatory factors such as TNF-alpha [SMD = -3.53, 95% CI (-5.05, -2.01), I-2 = 97%, P < 0.00001, very low certainty], CRP [SMD = -4.95, 95% CI (-6.56, -3.34), I-2 = 97%, P < 0.00001, very low certainty], IL-6 [SMD = -2.95, 95% CI (-3.49, -2.40), I-2 = 67%, P < 0.00001, very low certainty], and PCT [MD = -1.26 mu g/L, 95% CI (-1.28, -1.24), I-2 = 98%, P < 0.00001, very low certainty], as well as improved FEV1 [MD = 0.53 L, 95% CI (0.25, 0.80), I-2 = 96%, P = 0.0002, very low certainty] after treatment. There was no statistically significant difference between the groups in levels of the IL-8, FEV1/FVC, FVC, CD4(+), CD8(+), and CD4+/CD8+ ratio. Additionally, no significant differences were observed in the incidences of overall adverse reactions, nausea and vomiting, diarrhea, rash, and dizziness (P > 0.05). Conclusion: XFG provides benefits to children with AB regarding its effectiveness and does not increase the safety risks associated with TWM treatment. However, well-designed clinical trials are still essential.

Background:While gut microbiota dysbiosis has been associated with thyroid disorders, its causal role in goiter pathogenesis remains unclear. We aimed to investigate whether specific gut microbial taxa causally influence goiter risk through the short-chain fatty acid (SCFA)-iodine-thyroid axis. Methods:We performed Mendelian randomization (MR) analysis using gut microbiota genome-wide association study (GWAS) data (MiBioGen consortium, n = 18,340) and goiter GWAS data (FinnGen R10, 10,312 cases/401,869 controls). Experimental validation included: (1) establishing a propylthiouracil (PTU)-induced goiter rat model with 16S rRNA sequencing of fecal samples, (2) targeted SCFAs quantification, (3) thyroid/serum iodine measurement, (4) thyroid hormone assays, and (5) sodium-iodide symporter (NIS) protein expression analysis. Results:MR analysis identified 10 gut microbial taxa causally associated with goiter risk (all p < 0.05), with Bifidobacterium bifidum showing protective effects (OR = 0.861, 95% CI: 0.764-0.971, p = 0.014). In goiter rats, 16S rRNA sequencing revealed eight differentially abundant microbial taxa including significantly reduced B. bifidum, accompanied by: (1) impairment of two butyrate synthesis pathways, (2) decreased levels of six SCFAs (including butyrate), (3) impaired thyroid iodine uptake, (4) downregulated NIS expression, and (5) thyroid dysfunction [reduced triiodothyronine (T3), thyroxine (T4), free T3 (FT3), free T4 (FT4) with elevated thyroid-stimulating hormone (TSH)] - all measurements showing statistical significance (p < 0.05). Conclusion:This study provides causal evidence that Bifidobacterium depletion may contribute to goiter development through SCFA-mediated impairment of NIS-dependent iodine uptake and thyroid hormone synthesis, highlighting the association of the "gut-thyroid axis" and laying the foundation for early prevention and therapeutic intervention of goiter.

Background: "Gansui Banxia decoction" (GBD) is a classical traditional Chinese medicine formula for treating abnormal accumulation of fluid, such as malignant ascites (MA). Although GBD has shown definite waterexpelling effects, its exact underlying mechanism has not been elucidated. Purpose: This study aimed to investigate the drug effects of GBD on MA rats and its underlying mechanisms. Methods: The main chemical composition was determined by ultra-high performance liquid chromatography. The drug effects of GBD was evaluated in the established cancer cell-induced MA rat model. The symptoms were analyzed, and biological samples were collected for detecting immune and inflammation-related indicators by enzyme-linked immunosorbent assays, western blot, and flow cytometry. Results: GBD increased urine discharge, decreased ascites production, and alleviated cachexia. After GBD treatment, the expression of TLR4, MyD88, and NF-kB and the release of pro-inflammatory cytokines such as interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were reduced. In addition, GBD increased G1 phase arrest and inhibit excessive proliferation of cells in bone marrow while alleviating G1 phase arrest and increasing proliferation of cells in the thymus. Correspondingly, the development and maturation of T cells also changed. GBD increased the proportion of mature T-cells (CD4+CD8- and CD4-CD8+ single-positive (SP) T-cells), and decrease the proportion of immature cells (CD4+CD8+ double-positive (DP) T-cells and CD4-CD8- doublenegative (DN) T-cells) in the blood or tumor microenvironment (TME, the ascites microenvironment). Finally, we further analysis of immune cell subsets, GBD decreased the proportion of immunosuppressive T-cells in the blood (CD4+CD25+Foxp3+ T-cells) and TME (CD8+CD25+Foxp3+ T-cells), and increased the proportion of antitumor immune cells (CD8+CD28+ T-cells and NK cells) in the TME. Conclusion: These findings indicated that the drug effects of GBD were attributed to regulating the immuneinflammatory homeostasis, thereby mitigating the destruction of cancer cells and reducing the generation of ascites, which provided theoretical support for the clinical rational application and extended the scientific connotation of "water-expelling" of GBD.

ETHNOPHARMACOLOGICAL RELEVANCE:Haizao Yuhu decoction (HYD) is a classic Chinese herbal formula described in the surgical monographs of the Ming Dynasty "Waikezhengzong." It has been widely used to treat goiter for approximately 500 years and found to be particularly effective. HYD contains glycyrrhiza and sargassum. This pair of herbs belongs to "18 incompatible medicaments" of traditional Chinese medicine theory. Although these two herbs are opposite, our preliminary study proved that they have superior effect when added into HYD at 2 times the dose of Chinese Pharmacopoeia. However, the species of glycyrrhiza in HYD that are the most effective have not been recorded in ancient Chinese medical texts. According to the Chinese Pharmacopoeia, glycyrrhiza is divided into the following three species: Glycyrrhiza uralensis Fish., G. glabra L., and G. inflata Bat. The effect of HYD containing different species of glycyrrhiza and their mechanisms remain to be further explored.AIM OF THE STUDY:To investigate the effect of HYD containing three species of glycyrrhiza on goiter, and to elucidate the molecular mechanism using network pharmacology combined with RNA sequencing (RNA-seq).MATERIALS AND METHODS:A rat model of goiter was established by 14 days of intragastric gavage of propylthiouracil (PTU), and the rats were treated for 4 weeks with HYD containing three different species of glycyrrhiza. The body weight and rectal temperature of rats were tested weekly. At the end of the experiment, the serum and thyroid tissues of rats were collected. The effect of the three HYDs was assessed based on general observations (including body weight, rectal temperature, and living status of rats), absolute/relative thyroid weight, thyroid function (including triiodothyronine, thyroxine, free triiodothyronine, free thyroxine, and thyroid-stimulating hormone levels), and thyroid tissue pathology. Next, we explored their pharmacological mechanisms using network pharmacology combined with RNA-seq and validated key targets using real-time quantitative reverse-transcription polymerase chain reaction (RT-qPCR), western blotting (WB), and immunofluorescence (IF) assays.RESULTS:The three HYDs reduced the absolute/relative weights of thyroid tissues and improved the pathological structure, thyroid function, and general findings of rats with goiter. Overall, the effect of HYD-G. uralensis Fish. (HYD-U) was better. Results from network pharmacology and RNA-seq jointly suggested that both the pathogenesis of goiter and the mechanism of action of HYD for goiter were related to the phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway. We validated the key targets in the pathway, namely, vascular endothelial growth factor (VEGF) A, VEGF receptor 2, phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) and its encoded protein PI3K (p85), AKT serine/threonine kinase 1 (AKT1), phospho-AKT and cyclin D1 using RT-qPCR, WB, and IF assays. The PI3K-Akt pathway was hyperactivated in rats with PTU-induced goiter, whereas the three HYDs could inhibit the pathway.CONCLUSION:This study confirmed the definite effect of the three HYDs in the treatment of goiter, and HYD-U was found to be more effective. The three HYDs inhibited angiogenesis and cell proliferation in goiter tissue by inhibiting the PI3K-Akt signaling pathway.

Whether“eighteen incompatible medicaments”（a term in Chinese medicine， also called “eighteen clashes”） can be used together has been debated endlessly in past dynasties， and no unified conclusion has been formed. A systematic and long-term experimental research performed by the group led by the author ， on two classical prescriptions， including Haizao Yuhu Decoction and Banxia Gansui Decoction. It was found that different proportions， dosages， processing variations， modes of administration， times of administration， and species of the compatibility between liquorice root and seeweed， and between gansui root and liquorice root， were the factors affecting the "anti" and "non-anti，" and in each condition， there were suitable applications. Specifically， in each condition， there were conditions that were suitable for application and deemed appropriate， and conditions that were not suitable for application and deemed contraindicated. This showed that "the eighteen incompatible medicaments" is not an absolute contraindication. The eighteen incompatible medicaments" is not an absolute. The results of experimental studies have also shown that there are conditions for contraindications， and under certain conditions， reduced effectiveness can also occur. It can be concluded that "the eighteen incompatible medicaments" is a conditional "anti，" but it is not an absolute contraindication， and there are certain conditions and certain scopes for the combination of anti-drugs to be used together.

中药归经理论是中药药性理论体系的重要组成部分,归经表征了中药的作用部位,对中医药疗效发挥的机理阐释具有重要意义.文章主要梳理了中药归经理论的历史沿革、对相关的现代文献研究和实验研究进展进行归纳和总结,并进行了相关思考,提出了相应的问题和建议.梳理发现,归经理论经历了萌芽、奠基起源、形成、发展和完善时期,中药归经的文献研究主要集中在归经理论的梳理考证以及创新理论的形成和阐释,实验研究主要集中在利用多种现代科技手段或借助先进学说探讨归经.建议在今后的研究中加强归经理论文献研究的系统性、重脏腑经络功能、基于临床实践探讨归经、在中医药理论指导下进行中药归经的实验研究、重视方剂的归经研究,并应加强多学科与多种先进技术联合探讨归经.

目的：观察葛花、枳椇子及其配伍对急性酒精性肝病的改善作用，为临床用药提供科学依据，并为开展其他酒精性相关疾病的研究提供思路和借鉴方法：采用一次性灌胃给予56%（V/V）红星二锅头酒(0.012 mL·g -1 )建立小鼠急性酒精性肝损伤模型，120只雄性ICR小鼠按体重随机分成空白组、模型组、水飞蓟宾组、葛花组、枳椇子组、葛花枳椇子配伍Ⅰ（配伍比例为1:1）组、葛花枳椇子配伍Ⅱ（配伍比例为1:2）组、葛花枳椇子配伍Ⅲ（配伍比例为2:1）组，每组15只。各给药组按0.01 mL· g -1 预防性灌胃相应药物3 d，除空白组外，其余各组小鼠按0.012 mL·g -1 分别灌胃给予二锅头酒，于酒后12 h处死小鼠，并观察药物对小鼠肝功能、抗氧化应激能力的影响；苏木素-伊红（HE）染色观察肝脏病理变化；蛋白免疫印迹法（Western blot）检测各组小鼠Kelch样ECH相关蛋白1（Keap1）-核转录因子E2相关因子2（Nrf2）-抗氧化响应元件（ARE）信号通路相关蛋白表达；实时荧光定量聚合酶链式反应（Real-time PCR）检测相关基因表达。结果：与正常组比较，模型组小鼠血清中丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、碱性磷酸酶（ALP）水平，肝组织中丙二醛（MDA）、活性氧（ROS）含量显著升高（P＜0.01）；谷胱甘肽（GSH）、超氧化物歧化酶（SOD）活性显著性降低（P＜0.01）。与模型组比较，葛花-枳椇子（2:1）组小鼠ALT、AST和ALP水平显著减低（P＜0.01），肝脏组织中MDA、ROS水平均显著减低（P＜0.01），GSH、SOD水平均显著升高（P＜0.01）；肝脏脂肪变损伤均减轻，显著上调Nrf2 mRNA及蛋白表达（P＜0.01），显著下调Keap1 mRNA及蛋白表达（P＜0.01）。结论：葛花、枳椇子及其配伍组合对小鼠急性酒精性肝损伤有一定的预防作用，其机制可能与调控肝脏内Keap1/Nrf2/ARE信号通路，恢复并上调由乙醇所破坏的肝脏氧化平衡有关，从而有效遏制酒精性肝病的发展。

Objective: To explore the effect of modified Haizao-Gancao anti-drug combination of Haizao Yuhu Decoction（HYD） on the expression of genes related to PI3K/Akt pathway in goiter rats under the condition that the dosage of Haizao and Gancao is twice the high limit dosage prescribed in the Pharmacopoeia of the Pharmacopoeia of the People’s Republic of China 2015 Edition. Methods: A total of 84 rats were randomly divided into: blank group, model group, positive drug euthyrox group,HYD group, HYD without Haizao group, HYD without Gancao group and HYD without Haizao and Gancao group, 12 rats in each group. The propylthiouracil（PTU） was used to establish the model of goitre, then, each group were given the corresponding oral liquid. Apoptosis was detected by TUNEL method, apoptosis index was calculated, and expression of PI3K, Akt, Cyclin D1and Bcl-2 mRNA were detected by real-time quantitative PCR, the protein expression of Akt, p-Akt were detected by Western Blot. Results: Compared with the model group, the apoptosis index of the HYD group was distinctly rised（P＜0.05）, the mRNA expression level of PI3K, Cyclin D1 and Bcl-2 showed varying degrees of decline in the groups which were given interventional medicine（P＜0.01, P＜0.05）, the expression of AKT mRNA was significantly decreased in the HYD group and HYD without Haizao and Gancao group（P＜0.05）, the expression of p-Akt, p-Akt/Akt protein was significantly decreased in the groups which were given interventional medicine（P＜0.01, P＜0.05）. Conclusion: Anti-drug combination of Haizao Yuhu Decoction modified Haizao or Gancao on propylthiouracil induced goiter rats have a significant therapeutic effect, decreasing the expression of PI3K and Akt genes, thus affecting the expression of Cyclin D1 and Bcl-2, inhibiting cell proliferation and promoting cell apoptosis, so it acts as an anti-goiter.

Objective: To explore the improvement effect of Flos Puerariae, Hoveniae Semen, and their compatibility on acute alcoholic gastric mucosal injury, and lay a foundation for further development of Flos Puerariae, Hoveniae Semen, and their compatibility in the prevention and treatment of alcohol-induced multiple organ injury. Method: The acute alcohol-induced gastric mucosal injury model of mice was established by multiple intragastric administration of 56% Hongxing Erguotou liquor(15 mL·kg -1 ). A total of 120 male ICR mice were randomly divided into 8 groups, namely, the blank group, model group, omeprazole group(0.026 g·kg -1 ), Flos Puerariae-Hoveniae Semen（compatibility） high, medium, and low-dose groups(29.2,14.6, 7.3 g·kg -1 ), Flos Puerariae group(19.5 g·kg -1 ), and Hoveniae Semen group(19.5 g·kg -1 ), with 15 mice in each group. After one week of adaptive feeding, the animals were pre-administrated with the corresponding drug at the rate of 10 mL·kg -1 for 3 d. From the 4th day, after 1 h of administration, Erguotou liquid was administrated at the rate of 15 mL·kg -1 and the blank group was administrated with the same volume of deionized water to record the drunkenness and sober up time. The administration was lasted for 3 d. One hour after the last administration, the eyeballs were removed and the mice were sacrificed. The concentration of ethanol in serum was determined by gas chromatograph, and the activity of ethanol dehydrogenase（ADH） in gastric mucosa was determined by ultraviolet-vis spectrophotometer. Hematoxylin-eosin（HE） staining was used to observe the pathological changes in gastric mucosa. Serum inflammatory factors were determined by enzyme-linked immunosorbent assay（ELISA）. The mRNA expression of nuclear transcription factor-κB（NF-κB） p65 and NF-κB inhibitory protein α（IκBα） were detected by real-time polymerase chain reaction（Real-time PCR）.Result: As compared with the normal group, the content of interleukin-6（IL-6）, interleukin-1β（IL-1β）, and tumor necrosis factor-α（TNF-α） in serum of mice in the model group was increased（P＜0.05）, the mRNA expression of NF-κB p65 in gastric mucosa tissues was increased（P＜0.01）, and the mRNA expression of IκBαwas decreased（P＜0.01）. As compared with the model group, the drunkenness time of the omeprazole group, high and medium-dose compatibility groups, and Flos Puerariae group was prolonged（P＜0.05）, the sober up time of the high and medium-dose compatibility groups was shortened（P＜0.05）, the ethanol concentration in the serum of the high-dose compatibility group was decreased（P＜0.05）, the ADH activity in the gastric mucosa of the omeprazole group and high and medium-dose compatibility groups was increased（P＜0.05）, the macroscopic injury score of the high, medium, and low-dose compatibility groups and Flos Puerariae group was decreased（P＜0.05）, the score of pathological injury in the omeprazole group, high, medium, and low-dose compatibility groups, and Flos Puerariae group was decreased（P＜0.01）, the expression of IL-6 in serum of all drug groups was decreased（P＜0.05）, the expression of IL-1β in serum of the omeprazole group, high, medium, and low-dose Flos Puerariae groups, and Hoveniae Semen group was decreased（P＜0.05）, the expression of TNF-α in serum of high and medium-dose groups was decreased（P＜0.05）, the mRNA expression of NF-κB p65 in gastric mucosa tissues of all drug groups was decreased（P＜0.05）, and the mRNA expression of IκBα in gastric mucosa tissues of the omeprazole group and high, medium, and low-dose compatibility groups was increased（P＜0.05）. As compared with the high-dose compatibility group, the drunkenness time in the low-dose compatibility group and Hoveniae Semen group was shortened（P＜0.01）, the sober up time in the Flos Puerariae and Hoveniae Semen groups was prolonged（P＜0.01）, the concentration of ethanol in the serum of the medium and low-dose compatibility groups, Flos Puerariae group, and Hoveniae Semen group increased（P＜0.05）, the macroscopic injury score of the medium and low-dose compatibility groups and Hoveniae Semen group was increased（P＜0.05）, the pathological injury score of the medium and low-dose compatibility groups, Flos Puerariae group, and Hoveniae Semen group was increased（P＜0.01）, the content of IL-1β in serum of lowdose compatibility group, Flos Puerariae group, and Hoveniae Semen group was increased（P＜0.01）, and the mRNA expression of IκBα in gastric mucosa of the Flos Puerariae group and Hoveniae Semen group was decreased（P＜0.05）. As compared with the medium-dose compatibility group, the drunkenness time in the Hoveniae Semen group was shortened（P＜0.05）, the sober up time in the Flos Puerariae group was prolonged（P＜0.05）, the pathological injury score in the Flos Puerariae group and Hoveniae Semen group was increased（P＜0.01）, and the content of IL-1β in serum of the low-dose compatibility group, the Flos Puerariae group, and Hoveniae Semen group was increased（P＜0.05）. As compared with the low-dose compatibility group, the pathological injury score of the Hoveniae Semen group was increased（P＜0.05）. Conclusion: Flos Puerariae, Hoveniae Semen, and their compatibility play a role in preventing and treating acute alcoholic gastric mucosal injury in mice, which may be related to the inhibition of the expression of NF-κB signal pathway in gastric mucosa, and the high-dose compatibility group has the optimal effect.

心脑血管病变如冠心病心绞痛、脑卒中等的发生率逐年升高且有年轻化趋势,对人类生命健康产生重要影响.其发病因素主要包括气虚、气滞、痰浊、阴虚、血瘀等.本文以"气血理论、经络学说、心脑相通、异病同治"等理论为指导,阐释了气血-脉络-心脑的关系网络,并进一步从药物组成的功效及其现代药理作用两个层面分析了脉络通胶囊/颗粒的组方原理,以期为心脑血管疾病的防治作出有益探索.

ETHNOPHARMACOLOGICAL RELEVANCE:Glycyrrhiza and sargassum are among the 18 incompatible medicaments according to traditional Chinese medicine (TCM) theory. Although it contains glycyrrhiza and sargassum, Haizao Yuhu decoction (HYD) is a classic prescription widely used as TCM to treat goiter. According to the Chinese Pharmacopoeia, glycyrrhiza is divided into three varieties: Glycyrrhiza uralensis Fish., Glycyrrhiza glabra L., and Glycyrrhiza inflata Bat. Whether the three varieties of glycyrrhiza have different efficacy or toxicity when applied in the HYD is unknown.AIM OF THE STUDY:To explore whether the HYDs comprising three varieties of glycyrrhiza have different efficacy or toxicity when used to treat goiter in rats and the underlying mechanisms of these HYDs.MATERIALS AND METHODS:For two weeks, the goiter model was replicated by intragastric propylthiouracil (PTU) administration. Samples were divided into the control group, model group, euthyrox group, HYD with glycyrrhiza uralensis (HYD-U) group, HYD with glycyrrhiza glabra (HYD-G) group, and HYD with glycyrrhiza inflata (HYD-I) group. After four weeks of treatment, body weight, rectal temperature, thyroid/liver/kidney coefficient, thyroid/liver/kidney function, thyroid/liver/kidney histomorphology, and thyroid ultrastructure were evaluated. Then, real-time quantitative reverse-transcription polymerase chain reaction (RTqPCR), Western blot, and immunofluorescence analyses were performed to detect genes and proteins affecting autophagy and apoptosis in thyroid cells in the AMP-activated Protein Kinases (AMPK)/Mammalian target of rapamycin (mTOR) pathway.RESULTS:All three HYDs increased thyroid hormones (THs) levels, relieved thyroid pathological tissue and ultrastructure, and activated vital proteins and genes in the AMPK/mTOR pathway. Comparisons among the efficacy of the three HYDs indicated that HYD-U restored the THs most effectively; however, no difference in the anti-goiter effect was observed. Moreover, the three HYDs resulted in no toxicity and promoted the recovery of impaired liver and kidney function caused by PTU. Comparisons among the recovery effects of the three HYDs on the liver and kidney were the same.CONCLUSION:Our experiments demonstrated that the three HYDs had outstanding anti-goiter effects and protected liver and kidney function. Their anti-goiter effects were attributed to AMPK/mTOR pathway-induced autophagy and apoptosis. HYD-U resulted in the best THs recovery. It was further indicated that in our present study, glycyrrhiza and sargassum were compatible in the three HYDs, thereby suggesting their safety of compounding in HYD and providing a basis for the research of the 18 incompatible medicaments.

对北京中医药大学民族医学博士研究生培养现状进行分析,发现招生制度、导师队伍、培养机制及培养目标等方面仍存在不足.针对上述问题,提出优化招生制度、加强师资队伍建设等措施,为我国民族医学高等人才的招收和培养建言献策.

目的 通过研究海藻甘草反药组合在海藻玉壶汤中的加减应用对甲状腺肿大模型大鼠甲状腺功能及哺乳动物雷帕霉素靶蛋白(mTOR)表达的影响,为海藻甘草反药组合配伍应用提供实验依据.方法 选取雄性Wistar大鼠84只,随机分为空白组、模型组、优甲乐组(20.00μg/kg)、海藻玉壶汤组(10.08 g/kg)、海藻玉壶汤减海藻组(9.00 g/kg)、海藻玉壶汤减甘草组(9.18 g/kg)和海藻玉壶汤减海藻甘草组(8.10 g/kg),除空白组其余各组给予丙硫氧嘧啶复制甲状腺肿大病理模型,以优甲乐作为阳性对照药,其余各组给予相应药液.采用放射免疫法检测各组大鼠血清三碘甲状腺原氨酸(T3)、甲状腺素(T4)、促甲状腺激素(TSH)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)水平,免疫组化法检测甲状腺组织Ki67蛋白表达情况,Western blot检测甲状腺组织磷酸化哺乳动物雷帕霉素靶蛋白(p-mTOR)、mTOR蛋白表达情况.结果 与模型组比较,优甲乐组大鼠血清T3、T4、FT3、FT4水平升高,TSH水平降低(P<0.01);海藻玉壶汤组及各拆方组大鼠血清T3、T4、FT3、FT4水平升高(P<0.05,P<0.01),TSH水平降低(P<0.05,P<0.01).与模型组比较,海藻玉壶汤组、海藻玉壶汤减海藻组大鼠甲状腺组织Ki67蛋白阳性表达率降低(P<0.01),海藻玉壶汤减甘草组、海藻玉壶汤减海藻甘草组大鼠甲状腺组织Ki67蛋白阳性表达率降低(P<0.05).与模型组比较,优甲乐组、海藻玉壶汤减海藻组、海藻玉壶汤减甘草组p-mTOR蛋白表达水平降低(P<0.05),海藻玉壶汤组p-mTOR蛋白表达水平降低(P<0.01).mTOR蛋白表达水平各组之间比较差异无统计学意义.海藻玉壶汤减海藻组和海藻玉壶汤减甘草组p-mTOR/mTOR降低(P<0.05).结论 海藻玉壶汤对甲状腺肿大模型大鼠甲状腺激素水平具有明显的回调作用,且可能通过抑制mTOR信号通路的激活进而抑制细胞增殖,起到纠正甲状腺肿大的作用.

Bencao Tujing ( Illustrated Classic of Materia Medica ) is a brilliant and monumental compendium of materia medica by Su Song, which was published in 1061 and gathered ancestral knowledge from the Song dynasty as a legacy for posterity. The compendium emphasized the clinical applications of medicinal materials collected nationwide, which used illustrated atlases as references. The descriptions for each medicinal material subsumed the prescriptions containing it and were supplemented with relevant medical cases. Medical prescriptions predating the Song dynasty were included, which enhanced the clinical usefulness of the pharmacopoeia. The ancestral knowledge of materia medica was extensively merged with natural history throughout the compendium, which also made extensive reference to more than 200 Chinese classics, local gazetteers, and published works from the social and natural sciences. The inclusion of natural history and literature works changed the convention used in earlier pharmacopoeias to present medicines based solely on pharmacological analyses. The compendium also pioneered the inclusion of natural history in pharmacopoeia. Bencao Tujing helped establish China's leading position in the field of materia medica. Su Song's meticulous nature, truth-seeking attitude, and adherence to scientific thinking are truly worthy of emulation and promotion.

目的:从细胞色素(CY)P450酶的角度,以甘遂半夏汤复方为载体,探究腹水病理模型下甘遂甘草配伍"反"与"不反".方法:150只Wistar大鼠随机分为正常组、模型组、甘遂半夏汤全方组(5.68 g·kg-1·d-1)、甘遂半夏汤全方去甘遂组(5.57 g·kg-1·d-1)、甘遂半夏汤全方去甘草组(4.01 g·kg-1·d-1)、甘遂半夏汤全方去甘草甘遂组(3.90 g·kg-1·d-1),其中甘遂1.1 g、法半夏9 g、白芍15 g、炙甘草16.7 g、蜂蜜15 g,每组25只,除正常组外,其余各组大鼠腹腔注射Walker-256细胞复制大鼠癌性腹水模型,正常组、模型组灌胃蒸馏水,其余给药组灌胃相应药液,连续给药7 d;用高效液相色谱法(HPLC)检测探针药物浓度,通过计算代谢率来测定CYP450酶活性;用实时荧光定量聚合酶链式反应(Real-time PCR)测定CYP450酶基因表达;用蛋白免疫印迹法(Western blot)测定CYP450酶蛋白表达.结果:与正常组比较,模型组CYP1 A2、CYP2C9活性升高,CYP2E1、CYP2C19、CYP3A4 活性降低,CYP2E1、CYP2C19、CYP2C9、CYP3A4 mRNA 表达及 CYP2E1、CYP3A4 蛋白表达均降低(P＜0.05).与模型组比较,甘遂半夏汤全方组CYP2C9活性降低,CYP3A4 mRNA表达升高(P＜0.01);去遂组CYP1A2活性降低、CYP2E1、CYP3A4活性升高,CYP1A2、CYP2E1、CYP2C19、CYP3A4 mRNA表达及CYP2E1、CYP3A4蛋白表达升高(P＜0.05);去草组CYP2C9活性降低、CYP3A4活性升高,CYP2E1、CYP2C 19 mRNA表达升高(P＜0.05);双去组CYP2C9活性降低、CYP3A4活性升高、CYP3A4 mRNA表达升高(P＜0.01).与全方组比较,去遂组CYP2E1、CYP2C9、CYP3A4活性升高,CYP1A2、CYP2C19、CYP3A4 mRNA表达及 CYP3A4蛋白表达升高(P＜0.05);去草组 CYP2C9、CYP3A4活性升高、CYP2C19 mRNA表达升高,CYP3A4 mRNA表达降低(P＜0.05);双去组CYP2C9、CYP3A4活性升高(P＜0.01).结论:4个给药组在CYP450酶的角度均表现出一定的药效,其中全方去甘遂组效果最佳,优于全方组.甘遂甘草反药组合在甘遂半夏汤全方中未表现出"相反",但是有一定的减效作用,该实验条件下甘遂甘草配伍更接近于七情配伍中"相恶"的配伍关系.

目的 采用网络药理学方法分析"葛花-枳椇子"药对治疗酒精性肝病的药物成分、作用靶点、主要通路及生物过程,探讨其药效物质基础和配伍机制.方法 依托中药系统药理学分析平台(TCMSP)、中医药整合药理学研究平台v2.0(TCMIP)及Drugbank数据库检索葛花、枳椇子相关的化学成分和作用靶点,在UniProt蛋白数据库检索对应的人类蛋白基因,通过NCBI获取与酒精性肝病相关的疾病基因靶点信息,运用STRING平台构建PPI网络,并在Cytoscape中利用BINGO插件对靶点基因进行GO生物过程富集分析,利用DAVID生物学信息数据库对靶点进行KEGG信号通路分析,并绘制分子机制图.结果 本研究共获得21种化合物成分,这些成分靶点与酒精性肝病共有6个基因靶点、14条主要信号通路.参与的基因有ALDH2、IL6、TNF、HMOX1、HSPA5和MTTP;"葛花-枳椇子"药对治疗酒精性肝病主要参与Toll样受体信号(TLR)通路和NOD样受体信号(NLR)通路.结论 本研究初步验证了"葛花-枳椇子"药对治疗酒精性肝病的基本药理作用及相关机制,为进一步研究其作用机制奠定了基础.

甘草为多年生草本植物,为我国传统常用中药材.《中国药典》2020年版中收载甘草为乌拉尔甘草Glycyrrhiza uralensis、光果甘草G.glabra、胀果甘草G.inflata3个品种.不同品种甘草在某些化学成分上不仅存在含量上的差异,也存在种属特异性,药理活性也不尽相同.对不同品种甘草化学成分、药理作用的研究进展进行综述,并对其质量标志物(quality marker,Q-Marker)进行预测分析,建议将黄酮类化合物甘草苷、异甘草苷、甘草素、异甘草素和三萜类化合物甘草酸、甘草次酸作为3种甘草的Q-Marker.另外考虑到不同品种之间成分的特有性和各自的优势生物活性,建议可以将光甘草定作为光果甘草的Q-Marker,将查耳酮A作为胀果甘草的Q-Marker,以期为明确不同品种甘草Q-Marker及不同品种甘草药材质量标准建立及合理开发利用提供理论依据.