Background: Benzo[a]pyrene (BaP), a common food contaminant, is a recognized gastric carcinogen. This study aimed to identify therapeutic targets and repurposed drugs for gastric cancer (GC) using BaP as a network toxicology query. Methods: An integrated strategy combining network toxicology, multi-omics, machine learning (Random Forest, LASSO, SVM-RFE), and experimental validation was applied. Results: By intersecting GC-associated genes with BaP-related targets and machine learning, we identified three hub genes. The logistic regression model further revealed KCNE2 as a protective factor (OR = 0.515, 95% CI: 0.383–0.692), while SULF1 (OR = 2.940, 95% CI: 1.399–6.179) and TIMP1 (OR = 5.351, 95% CI: 2.020–16.743) were identified as potential risk factors. Survival analysis confirmed their prognostic significance. Single-cell transcriptomics descriptively showed TIMP1 and SULF1 enrichment in malignant/stromal cells and fibroblasts, respectively, whereas KCNE2 was restricted to normal epithelial cells and silenced in tumors. GSVA implicated epigenetic regulation, ECM remodeling, and TGF-β signaling. Molecular docking and dynamics simulations suggested that BaP can form stable complexes with DNMT1 and DNMT3A. Accordingly, drug enrichment analysis identified DNMT inhibitor 5-azacytidine as a top candidate. Cellular experiments confirmed that 5-azacytidine selectively inhibited GC cells and was associated with modulation of the DNMT3A–KCNE2 axis. Conclusions: Our findings provide a novel molecular target and a repurposed drug for GC from the perspective of a food contaminant.

Toll-like receptor 4 (TLR4) is a pivotal therapeutic target for inflammatory diseases and immune dysregulation. This study integrated artificial intelligence, molecular docking, dynamics simulations, and microscale thermophoresis (MST) to discover TLR4 inhibitors from medicinal food plants. A dataset of 890 TLR4 inhibitors from PubChem was utilized, with 445 molecular descriptors calculated using MOE 2022.02 software. Recursive feature elimination and four machine learning algorithms (linear discriminant analysis, support vector machines, logistic regression, and Lasso logistic regression) were employed for activity prediction. Furthermore, a model based on molecular fingerprints and graph fusion learning (FP&G) was developed for comparison. A chemical database of 6388 compounds was created enabling activity predictions. Traditional machine learning models demonstrated modest predictive accuracy of around 65 % with both sensitivity and specificity below 70 %, and Matthew's correlation coefficient (MCC) values under 0.5. In contrast, the FP&G learing model achieved predictive accuracies of 93.3 % on both the training and testing sets, respectively, with sensitivity and specificity of 94.0 % and 92.6 %, and a MCC value of 0.865. Our optimal model identified 283 compounds from 46 medicinal food plants as potential TLR4 inhibitors, with docking scores below -12.19 kcal/mol. Notably, goji berry contained the most number of TLR4 inhibitory components, which was consistent with its anti-inflammatory and antioxidant properties. Finally, molecular dynamics and MST revealed glyceryl trilinoleate stably binds TLR4's active site with strong affinity (Kd = 0.2 +/- 0.036 mu M) better than the classical TLR4 inhibitor C34's 33 +/- 11.7 mu M and high specificity. This comprehensive approach provided valuable tools and insights for future development of TLR4 inhibitors.

Background:Bile acids (BAs) play a crucial role in metabolic regulation, but their specific functions in metabolic syndrome (MS) remain unclear. Hyodeoxycholic acid (HDCA) has shown potential effects in non-alcoholic fatty liver disease (NAFLD), yet its role in MS is unexplored. Aim:This study aims to assess whether HDCA is a characteristic BA of MS and to investigate its intervention effects and potential mechanisms. Methods:We employed 16S rDNA sequencing and UHPLC-MS/MS to investigate the dynamics of the gut microbiota and BA profiles in rats and conducted a correlation study between indices, identifying HDCA as the potential characteristic BA. We then examined its interventional effects in MS rats comparing efficacy with the positive drug of MS (metformin). Subsequently, liver RNA sequencing (RNA-seq), gene set enrichment analysis (GSEA), and Wes Automated Simple Western assays were employed to investigate mechanisms of HDCA ameliorating MS. Results:HDCA was identified as a characteristic BA for MS, exhibiting a significant positive correlation with beneficial gut bacteria and a negative correlation with harmful bacteria, and highly inversely related to various abnormal MS indexes. HDCA treatment led to significant improvements in metabolic abnormalities in MS rats, with a central role in altering serum BA profiles and profoundly modifying the gut microbiome composition. The results of RNA-seq and GSEA indicated that HDCA influenced the expression of genes related to primary bile acid synthesis and fatty acid degradation (p<0.05). Wes assays validated that FXR, CYP7A1, CYP7B1, PPARα, CPT1, CPT2, FABP1, HMGCS1 and HMGCS2 proteins in MS rats exhibited significant changes after HDCA treatment (p<0.05), and this was more effective than metformin treatment. Conclusion:These study is the first to highlight HDCA as a therapeutic candidate for MS and provides new insights into the BA-MS axis, though further validation is needed.

OBJECTIVES:To investigate the therapeutic mechanism of Wendan Decoction for phlegm syndrome in rats with metabolic syndrome (MS). METHODS:Forty Wistar rats were randomly divided into normal control group (n=8) and 3 phlegm syndrome model groups (induced by high-fat, high-sugar, and high-salt feeding and a single-dose intraperitoneal STZ injection; n=24) treated with daily gavage of saline, Wendan Decoction (3.6 g/kg), or metformin (0.1 g/kg) for 4 weeks. General conditions and glucose and lipid metabolism parameters of the rats were monitored, and serum LPS, liver histopathology, hepatic expressions of FXR, CYP7A1 and FGFR4 and ileal expressions of FXR and FGF15 were examined. Gut microbiota structure was analyzed using 16S rDNA sequencing, and serum bile acids were quantified with UHPLC-MS/MS. RESULTS:The rat models of phlegm syndrome exhibited severe hepatic steatosis and necrosis, increased body weight, abdominal circumference, Lee's index, FBG, FINS, HOMA-IR, TG, TC, LDL and LPS, and decreased HDL level. The abundance of Bacteroidetes, Megamonas, and Bacteroides in gut microbiota increased while Firmicutes, Lachnospiraceae_NK4A136_group, isohyodeoxycholic acid, and glycohyodeoxycholic acid decreased significantly; hepatic FXR and FGFR4 expressions and ileal FXR and FGF15 expressions decreased while hepatic CYP7A1 expression increased significantly in the rat models. Treatment with Wendan Decoction effectively alleviated hepatic pathology, reduced body weight and abdominal circumference, improved glucose and lipid metabolic profiles and gut microbiota structure, and reversed the changes in hepatic and ileal protein expressions. Correlation analysis revealed that Firmicutes and Lachnospiraceae_NK4A136_group were positively correlated while Bacteroidetes, Megamonas and Bacteroides were negative correlated with the levels of isohyodeoxycholic acid and hyodeoxycholic acid. CONCLUSIONS:Wendan Decoction can significantly improve metabolic profiles in rats with phlegm syndrome of MS possibly by regulating the intestinal flora-bile acid axis to modulate the intestinal flora structure and maintain bile acid homeostasis via the FXR signaling pathway.

[This corrects the article DOI: 10.1371/journal.pone.0270593.].

Background: Ginseng-ophiopogon injection (GOI) is a clinically commonly used drug for Qi deficiency syndrome characterized by decreased physical function in China. This study aimed to clarify common pharmacological mechanisms of GOI in enhancing physical function. Methods: We performed an integrative strategy of weight-loaded swimming tests in cold water (5.5 °C), hepatic glycogen and superoxide dismutase (SOD) detections, GC-TOF/MS-based metabolomics, multivariate statistical techniques, network pharmacology of known targets and constituents, and KEGG pathway analysis of GOI. Results: Compared with the control group, GOI showed significant increases in the weightloaded swimming time, hepatic levels of glycogen and SOD. Additionally, 34 significantly differential serum metabolites referred to glycolysis, gluconeogenesis and arginine biosynthesis were affected by GOI. The target collection revealed 98 metabolic targets and 50 experimentreported drug targets of ingredients in GOI involved in enhancing physical function. Further, the PPI network analysis revealed that 8 ingredients of GOI, such as ginsenoside Re, ginsenoside Rf, ginsenoside Rg1, and notoginsenoside R1, were well-associated with 48 hub targets, which had good ability in enhancing physical function. Meanwhile, nine hub proteins, such as SOD, mechanistic target of Rapamycin (mTOR), and nitric oxide synthases, were confirmed to be affected by GOI. Finally, 98 enriched KEGG pathways (P<0.01 and FDR<0.001) of GOI were obtained from 48 hub targets of the PPI network. Among them, pathways in cancer, Chagas disease, lipid and atherosclerosis, and PI3K-Akt signaling pathway ranked top four. Conclusions: This study provided an integrative and efficient approach to understanding the molecular mechanism of GOI in enhancing physical function.

Thinking characteristics reflect the deep nature of human cultural phenomena. Traditional Chinese medicine（TCM） is an organic part of ancient Chinese traditional culture. As the core of TCM culture, TCM thinking is consistent with traditional Chinese thinking mode. Many thinking characteristics, such as emphasizing relationship and integrity, are reflected in the concept of TCM, clinical diagnosis and treatment, and academic research. The unique advantage of TCM comes from the comprehensive thinking mode based on holistic thinking. This paper explores the problems in the field of TCM syndrome research from its derived characteristics of ambiguity and complexity thinking, and proposes that the standardization of ’syndrome’ is the basis for improving the accuracy of syndrome differentiation, and the unification of syndrome differentiation method system and the formation of recognized syndrome differentiation standard are the necessary ways to solve the complexity of syndrome differentiation. The two researches of normalization and standardization should be strengthened to realize the development of syndrome differentiation research.

目的 探讨六君子汤治疗慢性萎缩性胃炎(CAG)大鼠的疗效和作用机制.方法 将22只SPF级Wistar大鼠根据体质量随机分为正常组5只和造模组17只.正常组不予造模,造模组予以0.1%氨水溶液及20 mmol/L脱氧胆酸钠溶液交替饮用联合饥饱失常法造模16周后,光镜下观察随机2只造模组大鼠胃黏膜组织形态改变以判定造模成功.造模组造模成功后根据体质量随机分为模型组、维酶素组、六君子汤组,每组各 5只.六君子汤组按体质量10 mL/(kg·d)灌胃0.405 g/mL六君子汤水煎液,维酶素组按体质量10 mL/(kg·d)灌胃24 mg/mL维酶素混悬液,正常组和模型组灌胃等剂量灭菌饮用水,连续干预4周.干预后观察4组大鼠一般情况和测量体质量,光镜下观察4组大鼠胃黏膜组织形态,ELISA法检测4组大鼠血清肿瘤坏死因子-α(TNF-α)含量,qPCR检测4组大鼠胃黏膜组织增殖细胞核抗原(PCNA)、血管内皮生长因子(VEGF)、嗜银蛋白(Ag-NOR)和促细胞凋亡基因(Bax)mRNA相对表达水平.结果 与正常组比较,模型组活动状况、毛发色泽、大便情况等均无改善,体质量较正常组降低(P＜0.01),胃黏膜腺体排列紊乱、萎缩,炎性细胞浸润,血清TNF-α含量及胃黏膜组织PCNA、VEGF、Ag-NOR、Bax mRNA相对表达水平均升高(P均＜0.05或0.01);与模型组比较,维酶素组及六君子汤组活动状况、毛发色泽、大便情况等均改善,体质量均升高(P均＜0.05),胃黏膜排列较紧密,腺体萎缩有所改善,炎症细胞浸润有所减少,血清TNF-α含量及胃黏膜组织PCNA、VEGF、Ag-NOR、Bax mRNA相对表达水平均降低(P均＜0.05或0.01).结论 六君子汤可以改善CAG大鼠胃黏膜病理形态,其机制可能与下调炎症因子TNF-α,抑制增殖因子PCNA、Ag-NOR、VEGF和促凋亡基因Bax的表达有关.

Background: Electroacupuncture is a common treatment for chronic atrophic gastritis (CAG) in China. We aimed to determine the effects of electroacupuncture at zusanli (ST36) on intestinal microbiota in CAG rats. Methods: In total, 42 SD rats were randomly divided into normal (NC, 10 rats) and model (MG, 32 rats) groups. Rats in the MG group were established as CAG disease models. After that, the rats in the MG group were randomly divided into CAG (10 rats), electroacupuncture (EA, 10 rats), and Vitacoenzyme (Vit, 10 rats) groups. Rats in the NC and CAG groups were subjected to a 30-min/d confinement for 4 weeks. Rats in the EA group were given electroacupuncture at zusanli for 30 min/d for 4 weeks. Rats in the Vit group were given Vitacoenzyme solution 10 ml/(kg d) for 4 weeks. Histopathological changes in the gastric mucosa were observed with hematoxylin and eosin staining, and the gene expression level of p53, Bcl-2, and c-myc was determined using the qPCR method. The 16S rDNA sequencing technique was used to determine structural changes and relative abundance expression of intestinal flora. Results: Compared with the NC group, gastric mucosal pathology in the CAG group revealed significant inflammatory infiltration, and the gastric mucosal lesions in the electroacupuncture group were improved remarkably; the expression of p53 and c-myc genes in the CAG group increased (p < 0.05), while the expression of Bcl-2 genes decreased (p < 0.05) in the EA group, that of p53 and c-myc genes decreased (p < 0.05), and that of Bcl-2 genes increased (p < 0.05). The abundance of bacteria such as Lactobacillus, Desulfobacterota, and Bacteroides pectinophilus group in the CAG group increased (p < 0.05), while that of bacteria such as Gastranaerophilales, Romboutsia, and Blautia decreased (p < 0.05). The relative abundance of Desulfobacterota and Helicobacter in the EA group decreased (p < 0.05), while that of probiotic bacteria such as Oscillospirales, Romboutsia, and Christensenellaceae increased (p < 0.05). Conclusion: Electroacupuncture at zusanli can promote the repair of pathological damage to the gastric mucosa in rats with CAG, and the mechanism might relate to the reduction in the relative abundance of harmful bacteria, increase in the relative abundance of intestinal probiotics, and regulation of the intestinal microbiota.

状态是中医健康认知的逻辑起点,它是对人在生命过程中特定阶段的健康状况及其发展趋势的描述,而整体动态个性化把握状态是维护健康的关键.根据Correa模式,在慢性萎缩性胃炎基础上伴发癌前病变,将明显增加发生胃癌的危险性,严重危害人民群众的健康.从中医健康管理的特点切入,根据慢性萎缩性胃炎患者的状态要素及病机演变规律,探讨慢性萎缩性胃炎患者的中医健康管理干预方式,以期经由中医健康管理调整状态,缓解慢性炎症的严重程度或缩短炎症持续时间,降低罹患胃癌的风险,为慢性胃炎的后续中医健康管理研究提供思路.

目的:探讨柴芍六君汤对肝郁脾虚型慢性萎缩性胃炎(CAG)大鼠刺猬(Hedgehog)信号通路的影响.方法:随机将Wistar大鼠分为正常组和造模组,造模组采用复合造模法进行构建肝郁脾虚型CAG大鼠模型,造模成功后,分为模型组,维酶素组,柴芍六君汤组,GDC-0449(阻滞剂)组,柴芍六君汤+GDC-0449组;正常组和模型组给予生理盐水灌胃,维酶素组和柴芍六君汤组分别给予240 mg·kg1·d-1,5.1 g·kg-1·d-1灌胃,GDC-0449组腹腔注射50 mg·kg-1·d.,柴芍六君汤+GDC-0449给予腹腔注射50 mg·kg-1·d-1和灌胃柴芍六君汤5.1g·kg-1·d-1,持续4周.苏木素-伊红(HE)染色观察大鼠胃黏膜病理形态,实时荧光定量聚合酶链式反应(Real-time PCR)和蛋白免疫印迹法(Westem blot)检测胃黏膜组织音猬因子(Shh),12次跨膜蛋白受体Patched1(Ptch1),胶质瘤相关肿瘤基因同源物1(Gli1)mRNA和蛋白表达,酶联免疫吸附测定法(ELISA)检测血清白细胞介素-1β(IL-1β),肿瘤坏死因子-α(TNF-α)含量.结果:与正常组比较,模型组大鼠腺细胞减少,腺体萎缩,腺腔体积增大,可见浆细胞浸润,伴有肠上皮化生,胃黏膜组织Shh,Ptch1,Gli1 mRNA和蛋白表达显著降低(P＜0.01),血清中IL-1β,TNF-α含量显著上升(P＜0.01).与模型组比较,维酶素组、柴芍六君汤组细胞排列较为整齐,腺体萎缩改善,未见明显炎性浸润,GDC-0499组和柴芍六君汤+GDC-0449组并无太多改善;维酶素组、柴芍六君汤组胃黏膜组织Shh,Ptch1,Gli1 mRNA和蛋白表达水平显著上升(P＜0.01),维酶素组血清中IL-1β含量差异无统计学意义,TNF-α含量显著降低(P＜0.01),柴芍六君汤组血清中IL-1β,TNF-α含量明显降低(P＜0.05,P＜0.01);GDC-0449组和柴芍六君汤+GDC-0449组,胃黏膜组织Shh,Ptch1,Gli1 mRNA和蛋白表达、血清中IL-1β,TNF-α含量差异无统计学意义.结论:柴芍六君汤能有效改善肝郁脾虚型大鼠胃黏膜病理学状态,其机制可能是通过激活Hedgehog信号通路,从而降低IL-1β,TNF-α含量有关.

目的:探究加味柴芍六君汤逆转慢性萎缩性胃炎(CAG)大鼠胃黏膜病理改变的炎症相关生物学机制.方法:将20只SD雄性大鼠随机分为正常组6只,造模组14只.采用化学诱导+饥饱失常的方法建立CAG大鼠模型,共16周,造模结束后随机取2只造模组大鼠进行模型评价.成模大鼠随机分为模型组和加味柴芍六君汤组,每组6只.正常组和模型组给予等体积(10 mL/kg)生理盐水灌胃,加味柴芍六君汤组给予0.69 g/mL加味柴芍六君汤灌胃,干预4周.观察胃黏膜病理形态变化,检测3组大鼠血清炎症因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)的含量及胃黏膜组织HIF-1αmR-NA表达水平.结果:正常组胃固有层腺体排列整齐,未见腺体萎缩、减少;模型组大鼠胃黏膜固有层腺体排列紊乱,局部腺体萎缩、减少,腺腔增大,炎性细胞浸润,可见多处散在出血点;加味柴芍六君汤组腺体排列较整齐,腺体萎缩改善,仍可见散在出血点.模型组大鼠血清IL-1β、IL-6含量显著升高(P<0.01),胃黏膜组织HIF-1αmRNA表达水平较正常组上升(P<0.05).加味柴芍六君汤组大鼠血清IL-1β、IL-6含量显著降低(P<0.01),HIF-1αmRNA表达水平较模型组显示出下降的变化趋势(P>0.05).结论:加味柴芍六君汤改善CAG胃黏膜组织病理的机制可能是通过降低血清IL-1β、IL-6含量,下调胃黏膜缺氧诱导因子-1α(HIF-1α)过表达,从而改善胃黏膜局部缺氧环境,减轻炎症反应.

目的 通过网络药理学的方法进行预测,再深一步进行动物实验验证来研究柴胡疏肝散治疗CAG的作用机制.方法 首先在TCMSP数据库中检索柴胡疏肝散的所有活性成分与药物靶点;通过收集PharmGkb、OMIM、GeneCards和DrugBank数据库中收录的慢性萎缩性胃炎的相关靶点.将药物靶点与疾病靶点进行映射筛选出交集靶点,将得到的交集靶点构建PPI网络与活性成分-共同靶点网络,并对其进行GO和KEGG富集分析.最后利用Vina软件进行分子对接实验验证,并通过免疫印迹法验证柴胡疏肝散对两种受体蛋白EGFR和STAT1的影响.结果 最终筛选得到柴胡疏肝散活性成分104个,潜在靶点238个,与慢性萎缩性胃炎的交集靶点52个;GO与KEGG富集分析分别得到2166条目和148条目,主要涉及到JAK-STAT信号通路、TNF信号通路、HIF-1信号通路等;分子对接结果显示EGFR、STAT1两个靶点能够与核心活性成分能够自发结合成较为稳定的构像;免疫印迹法实验证明柴胡疏肝散能够降低大鼠胃黏膜组织EGFR和STAT1蛋白表达.结论 通过网络药理学和实验验证,发现柴胡疏肝散可能通过调节EGFR和STAT1蛋白表达来共同调控胃黏膜细胞增殖与凋亡,进而发挥着治疗慢性萎缩性胃炎的效果,为深入进行柴胡疏肝散治疗慢性萎缩性胃炎的作用机制研究提供新思路和新方法.

目的 探讨柴芍六君汤对肝郁脾虚型慢性萎缩性胃炎(CAG)模型大鼠胃黏膜细胞增殖和凋亡因子的作用机制.方法 26只雌雄各半SD大鼠根据Excel随机生成数字分为正常组6只和造模组20只,造模组采用复合因素造模法建立肝郁脾虚型CAG大鼠模型并评价,成模后随机分为模型组、维酶素组、柴芍六君汤组,每组6只,正常组不予处理.干预过程中,柴芍六君汤组予柴芍六君汤5.1 g/(kg·d),维酶素组予维酶素混悬液240 mg/(kg·d),正常组和模型组予灭菌饮用水,分别灌胃4周.HE染色观察胃黏膜组织病理改变,qPCR法检测胃黏膜细胞凋亡基因c-myc和p53的表达,IHC法检测增殖因子PCNA和Ag-NOR含量,TUNEL法检测胃黏膜细胞凋亡指数.结果 与正常组比较,模型组大鼠活动度减少,病理显示胃黏膜固有腺体萎缩、炎性细胞浸润,胃黏膜c-myc、p53、PCNA、Ag-NOR表达以及凋亡指数均升高(P<0.05或P<0.01).与模型组比较,维酶素组和柴芍六君汤组大鼠活动度增加,胃黏膜病理萎缩均有一定程度改善、炎性细胞浸润减少;柴芍六君汤组大鼠胃黏膜c-myc、p53、PCNA、Ag-NOR表达以及凋亡指数均降低(P<0.05或P<0.01);维酶素组大鼠胃黏膜c-myc、p53表达均降低(P<0.05或P<0.01),PCNA、Ag-NOR蛋白表达及凋亡指数下降,差异均无统计学意义(P>0.05).与维酶素组比较,柴芍六君汤组大鼠一般情况及胃黏膜组织形态改善更明显,胃黏膜c-myc、p53 mRNA表达上升,PCNA、Ag-NOR蛋白表达及凋亡指数下降,差异均无统计学意义(P>0.05).结论 胃黏膜细胞增殖凋亡与CAG的发展演化关系密切,柴芍六君汤对肝郁脾虚型CAG大鼠胃黏膜具有良好的保护和修复作用,其作用机制可能与抑制c-myc、p53、PCNA以及Ag-NOR等表达,从而调节胃黏膜细胞过度增殖凋亡有关.

目的 利用网络药理学方法探讨加味柴芍六君汤治疗慢性萎缩性胃炎(CAG)的作用机制.方法 利用TCMSP数据库收集加味柴芍六君汤的有效活性成分和作用靶点,从GeneCards数据库中获取CAG作用靶点并将其与加味柴芍六君汤取交集,得到的加味柴芍六君汤治疗CAG靶点利用String数据库获取共同靶点的蛋白互作关系;随后利用Cytoscape 3.7.2软件绘制出中药有效活性成分-靶点-疾病网络图,再利用R软件对共同作用靶点进行GO生物学过程和KEGG信号通路富集分析.最后利用Vina1.1.2软件进行加味柴芍六君汤活性成分与核心靶点分子对接.结果 共获得加味柴芍六君汤有效活性成分195个,作用靶点265个,CAG作用靶点613个,药物-疾病共同靶点89个;GO生物学过程分析提示,加味柴芍六君汤参与磷酸酶结合、泛素样蛋白连接酶结合、细胞因子受体结合、受体配体活性、蛋白磷酸酶结合等生物学过程,KEGG信号通路和GO生物学过程富集分析筛选出加味柴芍六君汤参与HIF-1、PI3K-Akt、MAPK等152条信号通路.分子对接结果显示活性成分与核心靶点表现良好的亲和力,进一步证明研究结果的可靠性.结论 加味柴芍六君汤可能是通过抗炎,降低炎性因子IL-1β、IL-6的水平来减轻CAG黏膜细胞的缺氧状态,调节HIF-1α等细胞转录因子和蛋白的表达,或通过调控HIF-1、PI3K-Akt、MAPK等信号转导通路,从而改善胃黏膜瘀血,起到抗胃黏膜萎缩的作用.

目的 探讨切实可行的促进学生临床诊疗能力提升的课堂教学模式.方法 以我院中医学专业2017级本科生("5+3"一体化)共计121人为研究对象.对照组采用传统中医诊断模拟实训课的教学模式,实验组采取混合式翻转课堂教学模型.结果 实验组学生各项技能考试成绩和对教学的满意度均明显高于对照组(P<0.05).结论 构建以中医应诊能力和临床思辨能力培养为目标,应用性和实用性相结合的中医诊断临床模拟训练教学新模式,能深化教学改革,为中医人才分层次培养提供思路.

目的 采用网络药理学的方法探讨黄芪-白术治疗新型冠状病毒肺炎(新冠肺炎)的作用机制.方法 利用TCMSP数据库对黄芪-白术活性成分和作用靶点进行查找与筛选,获得黄芪-白术的有效活性成分和作用靶点,用Cytoscape 3.7.2软件绘制黄芪-白术的有效活性成分-作用靶点网络;利用GeneCards数据库获取新冠肺炎作用靶点,利用Venny 2.1.0在线工具,获得黄芪-白术与新冠肺炎共同作用靶点(即是黄芪-白术治疗新冠肺炎的作用靶点);利用String数据库构建和分析共同作用靶点互作网络;最后利用R软件对共同作用靶点进行GO和KEGG富集分析.结果 通过对黄芪-白术活性成分、作用靶点查找与筛选,获得黄芪-白术有槲皮素、山奈酚、蛇床子素、毛蕊异黄酮等19个有效活性成分,作用靶点189个,并绘制出黄芪-白术的有效活性成分-作用靶点网络图;用GeneCards数据库获取新冠肺炎作用靶点259个,经过Venny 2.1.0在线工具分析,获取41个黄芪-白术与新冠肺炎共同作用靶点;GO和KEGG富集分析提示:黄芪-白术参与细胞因子受体结合、细胞因子活性、受体配体活性、磷酸酶结合等生物学过程,可能通过调控IL-17、P53、HIF-1、B细胞、T细胞等信号通路而起到治疗新冠肺炎的作用.结论 黄芪-白术主要是通过抗炎、抗氧化及调节免疫而达到治疗新冠肺炎目的.

目的:采用网络药理学和分子对接探讨三棱-莪术治疗(CAG)的作用机制.方法:利用TCM-SP数据库收集三棱-莪术的活性成分和蛋白靶点,利用Uniprot数据库进行基因名转化,综合Gene-Cards、OMIM、PharmGKB和DrugBank数据库收集、筛选出CAG的相关靶点,与三棱-莪术作用靶点取交集,获取三棱-莪术与CAG的共同靶点;利用String数据库获取共同靶点的蛋白互作关系并且用Cytoscape软件进行可视化分析,随后利用Cytoscape软件绘制活性成分-共同靶点网络;最后利用R软件对共同靶点进行GO、KEGG富集分析和AutodockTool、Vina软件将核心活性成分和核心靶点进行分子对接.结果:获得三棱-莪术活性成分5个,蛋白靶点66个,疾病靶点377个,药物-疾病共同靶点9个,根据PPI与活性成分-共同靶点网络分析得到CASP3、PPARG、PTGS2、JUN、NOS2是核心靶点,且β-谷甾醇、芒柄花黄素是核心活性成分;GO和KEGG富集分析发现三棱-莪术可能通过对细菌源分子的反应、细胞对外界刺激的反应、死亡受体结合等发挥作用,其作用机制可能涉及IL-17信号通路、TNF信号通路、P53信号通路、HIF-1信号通路等,分子对接显示三棱-莪术主要活性成分与核心靶点有很好的结合能力.结论:该实验得出三棱-莪术可能是通过抗炎、调控细胞凋亡、抑制血管形成来达到治疗CAG的效果.

目的 从代谢组学角度探讨柴芍六君汤改善慢性萎缩性胃炎(CAG)肝郁脾虚证大鼠代谢紊乱的可能作用机制.方法 32只SD大鼠随机分为空白组10只、造模组22只.造模组采用化学诱导、饥饱失常和夹尾刺激法建立CAG肝郁脾虚证大鼠模型,造模10周后进行模型评价.将成模大鼠随机分为模型组和柴芍六君汤组,每组10只.柴芍六君汤组予浓度为0.51 g·mL-1柴芍六君汤10 mL·kg-1·天-1灌胃,空白组和模型组予等体积灭菌饮用水灌胃,共给药4周.一般行为学观察,苏木素-伊红(HE)染色观察胃黏膜组织病理形态,核磁共振氢谱技术(1H-NMR)识别胃黏膜组织代谢物表达变化,代谢通路分析.结果 造模组大鼠神态疲惫,行为抑郁,大便溏结不调,胃黏膜固有腺体明显萎缩、炎性细胞浸润,符合CAG肝郁脾虚证表现.经柴芍六君汤给药后,模型大鼠一般行为学和胃黏膜组织病理改善.1H-NMR代谢组学检测出15个与CAG肝郁脾虚证密切相关的胃黏膜组织代谢物,柴芍六君汤干预后回调泛酸、2-羟基丁酸、甲基丙二酸、甲硫醇、乳酸、N-甲基-α-氨基异丁酸、溶血磷脂酰胆碱、谷氨酸、N-乙酰基天冬氨酸、顺式5-四氢十六烷基肉碱、腺苷、脂质含量(P>0.05或P>0.01),共得到D-谷氨酰胺和D-谷氨酸代谢,丙氨酸、天冬氨酸和谷氨酸代谢,精氨酸生物合成代谢这3条关键代谢调节通路.结论 柴芍六君汤能够保护和修复CAG肝郁脾虚证模型大鼠胃黏膜,回调差异代谢物的紊乱,其主要治疗机制可能与D-谷氨酰胺和D-谷氨酸代谢、丙氨酸、天冬氨酸和谷氨酸代谢、精氨酸生物合成代谢通路调控有关.

目的 探讨柴芍六君汤治疗慢性萎缩性胃炎(CAG)肝郁脾虚证的可能作用机制.方法 42只SD大鼠随机分为空白组10只和造模组32只.造模组采用复合因素造模法建立CAG肝郁脾虚证大鼠模型.造模成功的30只大鼠随机分为模型组、维酶素组和柴芍六君汤组,每组10只.柴芍六君汤组予浓度为0.51 g/ml柴芍六君汤10ml/ (kg·d)灌胃,维酶素组予浓度为24 mg/ml维酶素混悬液10ml/ (kg·d)灌胃,空白组和模型组用等体积灭菌饮用水灌胃,干预4周.观察大鼠体质量、胃黏膜组织病理变化,检测胃黏膜组织核转录因子κB (NF-κB)、原癌基因(c-Myc) mRNA和转录活化蛋白1(STAT1)蛋白表达.结果 各组大鼠体质量增长情况比较,差异均无统计学意义(P＞0.05).模型组胃黏膜固有层腺体萎缩,排列稀疏紊乱,壁细胞和主细胞丢失,较多炎性浸润,NF-κB、c-Myc mRNA和STAT1蛋白表达较空白组显著上升(P＜0.01).柴芍六君汤组NF-κB mRNA和维酶素组c-Myc mRNA表达较模型组下降(P＜0.05),两组病变胃黏膜均有不同程度的改善,炎性浸润减轻,STAT1蛋白表达降低(P＜0.05或P＜0.01).柴芍六君汤组NF-κB mRNA表达较维酶素组下降(P＜0.05).结论 柴芍六君汤可以改善CAG肝郁脾虚证萎缩胃黏膜,其机制可能与抑制NF-κB/STAT1异常激活,下调胃黏膜组织NF-κB mRNA和STAT1蛋白过表达有关.