BACKGROUND:Dysregulated microbiota is a hallmark of end-stage liver disease (ESLD). This study aimed to elucidate the intrahepatic microbiome in hepatitis B virus (HBV)-related ESLD. METHODS:We collected liver tissue samples from patients undergoing liver transplantation due to decompensated cirrhosis (DC) (n = 20) or acute-on-chronic liver failure (ACLF) (n = 24), as well as 18 samples from donors. Metatranscriptomic sequencing was performed to profile liver microbiome and transcriptome. RESULTS:2208 bacterial species were detected across 13 phyla and 165 genera. Metatranscriptomic profiling revealed that Proteobacteria and Actinobacteria dominated the intrahepatic microbiome, with Escherichia coli and Pseudomonas most prevalent across groups. Principal coordinate analysis showed distinct microbial community structures among donors, DC, and ACLF patients. Compared with donors, both groups exhibited increased abundance of Bacteroides heparinolyticus, Moraxella osloensis, and Gardnerella vaginalis, while ACLF patients were further enriched with Alcaligenes faecalis and Burkholderia insecticola, and DC patients had higher B. heparinolyticus. Most taxa originated from the gut, with additional oral- and respiratory-derived species. Despite similar abundance between groups, E. coli in ESLD displayed marked functional activation, including nutrient acquisition systems and virulence factors linked to adhesion, invasion, and toxin production. Integrated host - microbiome analysis revealed taxa-specific associations with impaired hepatic metabolic, immune, and structural integrity. CONCLUSION:This study delineates the compositional and functional reprogramming of the intrahepatic microbiome in patients with ESLD and its coupling with liver metabolic, immune, and structural pathways. These findings suggest the intrahepatic microbiome as a promising therapeutic target for ESLD.

BACKGROUND:Metabolic-associated fatty liver disease (MAFLD) is a prevalent chronic liver condition globally, characterized by suboptimal treatment outcomes. Traditional therapies often fail to address the multifaceted pathogenesis of MAFLD, which involves lipid metabolism, inflammation, and gut-liver axis dysregulation. JiGuCao Capsule formula (JCF), a patented Chinese medicine, has demonstrated clinical efficacy in liver disease treatment, indicating its potential as a new therapeutic option for MAFLD. PURPOSE:This study aimed to investigate the therapeutic effects and underlying mechanisms of JCF in treating MAFLD, particularly focusing on its impact on liver pathology, intestinal health, and gut microbiota composition. METHODS:A MAFLD mouse model was developed by administering a high-fat diet and 5% fructose water for 16 weeks. At week 8, mice exhibited significant steatosis, inflammation, and insulin resistance. Fifty mice were allocated into two groups: the normal diet (ND) group with 19 mice and the high-fat feed diet (HFD) group with 31 mice. Seven mice from each group were sacrificed at week 8 for serological and histopathological assessments. The remaining mice were allocated into ND (n = 6), HFD (n = 6), HFD + JCFL (human equivalent dose,780 mg/kg, n = 6), HFD + JCFH (threefold the human equivalent dose, 2340 mg/kg, n = 6), HFD + Polyene Phosphatidylcholine (PPC) (human equivalent dose,177.84 mg/kg, n = 6) and ND+ JCF (human equivalent dose,780 mg/kg, n = 6) groups. Daily gavage started at week 9. At week 16, after fasting, body weight and liver condition were recorded, and mice were euthanized with pentobarbital sodium. Mouse tissues and feces were collected for histopathological, molecular biological, and multi-omics analyses. RESULTS:JCF effectively slowed MAFLD progression in mice by decreasing hepatic lipid accumulation and inflammation. Treatment with JCF significantly reduced hepatic triglycerides and inflammatory markers, including TNF-α and IL-6. JCF enhanced lipid metabolism, repaired the intestinal barrier, and lowered inflammatory cytokines in the intestines, as indicated by reduced serum LPS and restored tight junction proteins expression, such as claudin-1 and occludin. Fecal microbiota analysis indicated that JCF treatment elevated Lactobacillus levels and reduced Colidextribacter levels, correlating with enhanced metabolic profiles. The primary bioactive compounds identified in JCF responsible for these therapeutic effects were betulinic acid, cholic acid, deoxycholic acid, oleanolic acid, and pectolinarigenin. Transcriptomic analysis showed that JCF regulated key pathways involved in lipid metabolism, including the pparγ-cd36 axis and modulation of ox-LDL levels. The results indicate that JCF effectively mitigates MAFLD by influencing the gut-liver axis and lipid metabolism. CONCLUSION:JCF alleviates MAFLD by modulating the gut-liver axis and lipid metabolism. Its effects involve improving gut barrier function, regulating microbiota, and targeting the pparγ-cd36 axis. Active compounds like betulinic acid support its therapeutic potential. JCF shows promise as a novel treatment for MAFLD, with further clinical studies needed.

ABSTRACT Aims The TiaoGanXiaoZhi formula (TGXZ), a traditional Chinese medicine, has been shown to alleviate the progression of metabolic‐associated fatty liver disease (MAFLD) clinically. However, its underlying mechanism remains unclear. This study aimed to investigate the effects and mechanisms of TGXZ in treating MAFLD in mouse models. Methods The MAFLD mouse model was established using a high‐fat diet and 5% fructose water over 16 weeks. At Week 8, mice exhibited significant steatosis, inflammation, and insulin resistance. A total of 42 mice were divided into the normal feed diet (NFD) group (n = 18) and the high‐fat feed diet (HFD) group (n = 24). Six mice from each group were killed at Week 8 for serological and histopathological assessments. The remaining mice were allocated into NFD (n = 6), HFD (n = 6), HFD + TGXZ (n = 6), NFD + TGXZ (n = 6), and HFD + Placebo (n = 6) groups. TGXZ (or placebo) was administered at a clinical equivalent dose of 7.699 g/(kg·d) to the respective groups, while NFD and HFD groups received distilled water. Daily gavage started in Week 9. At Week 16, after fasting, body weight and liver condition were recorded, and mice were euthanized with pentobarbital sodium. Liver tissue was collected for further analysis, and the remaining tissue and feces were stored at −80°C. Data were graphed using GraphPad Prism 8.0.0 and analyzed with SPSS Statistics 25.0. Results are expressed as mean ± standard deviation. Statistical comparisons were made using Student's t‐test for two groups and one‐way ANOVA for more than two groups, with significance set at p < 0.05. Results Compared to the MAFLD mouse model group, TGXZ treatment significantly downregulated the weight of white adipose tissue (1.61 ± 0.66 vs. 3.06 ± 0.34 g, p < 0.0010), liver weight (1.22 ± 0.16 vs. 1.98 ± 0.39 g, p = 0.0031), and the levels of alanine aminotransferase (20.6 ± 3.4 vs. 46.1 ± 12.3 U/L, p < 0.0010), aspartate aminotransferase (99.9 ± 19.1 vs. 168.4 ± 34.3 U/L, p = 0.0014), cholesterol (2.95 ± 0.56 vs. 4.38 ± 0.34 mmol/L, p = 0.0053), triglycerides (2.25 ± 0.41 vs. 4.18 ± 0.67 mmol/L, p < 0.0010), low‐density lipoprotein (0.66 ± 0.11 vs. 1.41 ± 0.52 mmol/L, p = 0.0073), and total bile acid (0.71 ± 0.41 vs. 2.18 ± 0.61 mmol/L, p = 0.0017), except for high‐density lipoprotein (2.41 ± 0.81 vs. 2.55 ± 0.31 mmol/L, p = 0.5655). The liver transcriptome, fecal microbiota sequencing, and fecal lipidomics analysis demonstrated that TGXZ treatment improved the expression of genes related to lipid metabolism, alleviated intestinal microbiota disorders, and mitigated lipid disturbances caused by MAFLD. Conclusions Our study demonstrated that TGXZ treatment effectively alleviated the progression of MAFLD. The inhibitory effects of TGXZ on MAFLD may be attributed to its regulation of gut microbiota, lipid metabolism, and hepatic inflammation.

•Traditional Chinese medicine KXYA formula exerted an anti-HCC effect in vivo and in vitro.•Omics detection and experimental verification showed that KXYA inhibited HCC by reducing glutathione and inducing ferroptosis.•The key targets of KXYA treatment on HCC were UGDH, AKR1B10, and SLC7A11, which could be the therapeutic targets for HCC.

The JiGuCao capsule formula (JCF) has demonstrated promising curative effects in treating chronic hepatitis B (CHB) in clinical trials. Here, we aimed to investigate JCF's function and mechanism in diseases related to the hepatitis B virus (HBV). We used mass spectrometry (MS) to identify the active metabolites of JCF and established the HBV replication mouse model by hydrodynamically injecting HBV replication plasmids into the mice's tail vein. Liposomes were used to transfect the plasmids into the cells. The CCK-8 kit identified cell viability. We detected the levels of HBV s antigen (HBsAg) and HBV e antigen (HBeAg) by the quantitative determination kits. qRT-PCR and Western blot were used to detect the genes' expression. The key pathways and key genes related to JCF on CHB treatment were obtained by network pharmacological analysis. Our results showed that JCF accelerated the elimination of HBsAg in mice. JCF and its medicated serum inhibited HBV replication and proliferation of HBV-replicating hepatoma cells in vitro. And the key targets of JCF in treating CHB were CASP3, CXCL8, EGFR, HSPA8, IL6, MDM2, MMP9, NR3C1, PTGS2, and VEGFA. Furthermore, these key targets were related to pathways in cancer, hepatitis B, microRNAs in cancer, PI3K-Akt signaling, and proteoglycans in cancer pathways. Finally, Cholic Acid, Deoxycholic Acid, and 3', 4', 7-Trihydroxyflavone were the main active metabolites of JCF that we obtained. JCF employed its active metabolites to perform an anti-HBV effect and prevent the development of HBV-related diseases.

目的:基于临床试验注册资料,分析中国慢性乙型肝炎(CHB)的临床研究现状.方法:检索建库起至2020年12月31日在中国临床试验注册中心()注册的有关CHB临床研究,并进行挖掘分析.结果:共检索临床研究1282项,符合纳入标准的研究165项,包括干预性研究78项、观察性研究64项、病因学/相关因素研究16项、基础科学研究4项、预后研究1项、流行病学研究1项、诊断试验1项.结论:近年来中国慢性乙型肝炎的临床研究逐渐增多,研究以干预性研究为主.研究中干预措施可以分为针对"病毒因素为主"的抗病毒疗法和针对"宿主因素为主"的干扰素治疗、免疫疗法、粪菌移植治疗、中西医结合治疗等.临床研究致力于抗病毒方案的优化及治疗方案的多元化,中医药在其中发挥着越来越重要的作用.

外泌体是由细胞内多囊泡体形成,携带脂质、蛋白质、编码和非编码RNA以及线粒体DNA等多种生物大分子,在体内可由包括肝细胞、肝星状细胞和免疫细胞在内的不同细胞类型释放,起着细胞间通讯的作用.越来越多研究表明,外泌体参与了HBV感染导致的慢性乙型肝炎(CHB)及肝细胞癌(HCC)的发生、发展及转归,有望成为HBV感染相关性HCC的早期诊断及预后评估的潜在生物学标志物.本文综述了外泌体在HBV感染宿主过程中的作用及其在CHB和HCC的发生、发展及预后中的重要性,以期为该领域的基础和临床研究提供新思路.

目的 探讨荜铃胃痛颗粒治疗大学生功能性消化不良(Functional dyspepsia,FD)上腹痛综合征(Ep-igastric pain syndrome,EPS)的临床疗效.方法 选取2018年3月—2019年10月期间就诊于北京中医药大学东方医院、中国中医科学院西苑医院、山东省中医院、河北省中医院、天津中医药大学第一附属医院、天津中医药大学第二附属医院的符合中医气滞血瘀证的EPS大学生患者78例.采用随机数字表法随机分为安慰组和治疗组,每组各39例.治疗组给予荜铃胃痛颗粒口服,安慰组给予安慰剂口服.治疗6周后,观察两组患者视觉模拟评分量表(Visual Analogue Score,VAS)评分情况,上腹痛症状发作频率、缓解率、消失率及临床有效率,功能性消化不良生存质量量表(FDDQL)评分、铝碳酸镁片使用及不良反应情况.结果 治疗组治疗第2、3、4、5、6周后VAS评分均较治疗前降低,安慰组治疗第6周后VAS评分较治疗前降低,差异有统计学意义(P<0.05);且治疗组治疗第2、3、4、5、6周后VAS评分均较安慰组明显降低,差异有统计学意义(P<0.05).治疗组治疗第2、3、4、5、6周后上腹痛症状发作频率均较治疗前降低,安慰组治疗第5、6周后上腹痛症状发作频率较治疗前降低,差异有统计学意义(P<0.05);且治疗组治疗第3、4、5、6周后上腹痛症状发作频率均较安慰组明显降低,差异有统计学意义(P<0.05).两组患者治疗后治疗组上腹痛症状缓解率87.18％高于安慰组17.95％,两组比较,差异有统计学意义(P<0.05).治疗组治疗后上腹痛症状消失率为79.49％(31/39);安慰组上腹痛症状消失率为17.95％(7/39).治疗组上腹痛症状消失率明显高于安慰组,两组比较,差异有统计学意义(P<0.05).治疗后治疗组总有效率为100％(39/39)明显高于安慰组30.77％(12/39),两组比较,差异有统计学意义(P<0.05).治疗6周后两组患者FDDQL评分均较治疗前升高,差异有统计学意义(P<0.05);治疗组FDDQL评分较安慰组明显升高,差异有统计学意义(P<0.05).两组患者铝碳酸镁片使用率、使用量比较,差异无统计学意义(P>0.05).治疗期间,两组患者不良反应比较,差异无统计学意义(P>0.05).结论 荜铃胃痛颗粒不仅可以有效缓解不适症状、改善中医证候,还可以提高患者生存质量,且无严重不良反应,在治疗大学生EPS气滞血瘀证具有明显优势.

The Chinese traditional medicine KangXianYiAi formula (KXYA) is used to treat hepatic disease in the clinic. Here we aim to confirm the therapeutic effects and explore the pharmacological mechanisms of KXYA on hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). We first collected and analyzed clinical data of 40 chronic hepatitis B (CHB) patients with precancerous liver lesions under KXYA treatment. Then, the cell viability, migration, cell cycle, and apoptosis of HepAD38 cells with KXYA treatment were examined. Next, we performed network pharmacological analysis based on database mining to obtain the key target pathways and genes of KXYA treatment on HBV-related HCC. We finally analyzed the expression of the key genes between normal and HBV-related HCC tissues in databases and measured the mRNA expression of the key genes in HepAD38 cells after KXYA treatment. The KXYA treatment could reduce the liver nodule size of CHB patients, suppress the proliferation and migration capabilities, and promote apoptosis of HepAD38 cells. The key pathways of KXYA on HBV-related HCC were Cancer, Hepatitis B, Viral carcinogenesis, Focal adhesion, and PI3K-Akt signaling, and KXYA treatment could regulate the expression of the key genes including HNF4A, MAPK8, NR3C1, PTEN, EGFR, and HDAC1. The KXYA exhibited a curative effect via inhibiting proliferation, migration, and promoting apoptosis of HBV-related HCC and the pharmacological mechanism was related to the regulation of the expression of HNF4A, MAPK8, NR3C1, PTEN, EGFR, and HDAC1.

Background: Xiaoxianxiong decoction is a classic formula in traditional Chinese medicine used to treat type 2 diabetes mellitus and proven to be effective. But the material basis and underlying mechanisms remain unclear. The aim of the present study was to elucidate the potential effective material basis of Xiaoxianxiong decoction and molecular mechanism treating type 2 diabetes mellitus. Methods: The absorbed bioactive components were identified based on serum pharmacochemistry. Network analysis were performed to obtain effect targets for docking verification with the absorbed prototypes to determine the potential effective material basis. On the above basis, network pharmacology was conducted to explore the molecular mechanism. Results: 76 compounds were identified of Xiaoxianxiong decoction and 61 absorbed bioactive compounds were investigated. Serine/threonine kinase 1 and ALB were key targets acquired by network analysis for molecular docking. Subsequently, 5 compounds were considered as the potential effective material basis, namely berberine, berberrubine, lariciresinol and gingerenone A, jatrorrhizine. Further, the mechanism mainly lies in the insulin signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, AGE-RAGE signaling pathway in diabetic complications, phospholipase D signaling pathway to regulate blood glucose levels on target tissues as well as organs and exhibit anti-inflammatory, promote cell differentiation and cell growth, maintain oxygen homeostasis and affect the enzymes along with key metabolites. Conclusion:This integrated research strategy to investigate the treatment of Xiaoxianxiong decoction on type 2 diabetes mellitus provides valuable insights for further study and clinical practice of Xiaoxianxiong decoction.

Background and Aims: Chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) levels are at risk of disease progression. Currently, liver biopsy is suggested to identify this population. We aimed to establish a non-invasive diagnostic model to identify patients with significant liver inflammation. Method: A total of 504 CHB patients who had undergone liver biopsy with normal ALT levels were randomized into a training set ( n = 310) and a validation set ( n = 194). Independent variables were analyzed by stepwise logistic regression analysis. After the predictive model for diagnosing significant inflammation (Scheuer's system, G ≥ 2) was established, a nomogram was generated. Discrimination and calibration aspects of the model were measured using the area under the receiver operating characteristic curve (AUC) and assessment of a calibration curve. Clinical significance was evaluated by decision curve analysis (DCA). Result: The model was composed of 4 variables: aspartate aminotransferase (AST) levels, γ-glutamyl transpeptidase (GGT) levels, hepatitis B surface antigen (HBsAg) levels, and platelet (PLT) counts. Good discrimination and calibration of the model were observed in the training and validation sets (AUC = 0.87 and 0.86, respectively). The best cutoff point for the model was 0.12, where the specificity was 83.43%, the sensitivity was 77.42%, and the positive likelihood and negative likelihood ratios were 4.67 and 0.27, respectively. The model's predictive capability was superior to that of each single indicator. Conclusion: This study provides a non-invasive approach for predicting significant liver inflammation in CHB patients with normal ALT. Nomograms may help to identify target patients to allow timely initiation of antiviral treatment.

目的 探讨健脾疏肝方对非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)大鼠肝细胞的超微结构和肝功能的影响.方法 选取SPF级SD大鼠随机分为正常组、模型组、健脾疏肝方组(15.75 g/kg)、易善复组(137.3 mg/kg),采用高脂饮食法建立NASH模型,高脂饲料饲养8周同时给药.取血清检测谷丙转氨酶、谷草转氨酶和血脂水平;取大鼠肝组织制作病理切片、电镜标本,光镜下进行病理学观察,透射电镜下观察肝细胞的超微结构并对线粒体数量进行计数.结果 与模型组相比,健脾疏肝方组与易善复组血清肝酶及血脂水平均明显改善(P<0.05);电镜结果显示,与模型组相比,健脾疏肝方组线粒体数量较模型组增多(P>0.05),大部分线粒体结构较完整,内质网数量增多,结构清晰;易善复组线粒体数目较模型组明显增多(P<0.01),脂滴沉积较模型组与健脾疏肝方组减少,大部分线粒体形态恢复正常.结论 健脾疏肝方可能通过改善NASH大鼠肝功能,降低血脂水平,修复线粒体形态和功能,恢复内质网数量和形态,拮抗脂质过氧化诱导的氧化应激反应所导致的线粒体损伤、凋亡和内质网应激,进而改善NASH.

[目的]运用红外热成像技术探讨寒热错杂型非糜烂性胃食管反流病(NERD)之经穴红外热图特征及病证本质.[方法]收集2017年11月～2018年12月就诊于北京市宣武中医医院消化科、北京中医药大学东方医院消化科、解放军总医院第八医学中心中医科的30例NERD寒热错杂证患者与33例相对健康者,填写反流性疾病问卷(reflux diagnostic questionnaire,RDQ),对量表得分进行相关分析,并用红外热成像系统采集不同穴位/部位皮温,对2组温度进行统计分析.[结果]①观察组双侧肝俞穴、脾俞穴、胃俞穴相对温度均值显著低于对照组,差异有统计学意义(P＜0.05);②观察组左侧肝俞穴、脾俞穴、胃俞穴相对温度均值低于右侧的对应穴位,差异无统计意义(P＞0.05);③观察组整体温度较对照组低,尤其以左右肝俞穴、胃俞穴、脾俞穴温度差异最明显,差异有统计学意义(P＜0.05),从均值上看,观察组左右期门、左右天枢、左右足三里、肝、胃相对温度较对照组低,观察组左右巨髎、脾相对温度较对照组高.[结论]NERD寒热错杂证病机与肝、脾、胃三脏腑阳气不足有关,因阳气不足,内生郁滞,久而化热,形成上热下寒、外热内寒之寒热错杂、虚实交错之象,使疾病迁延不愈.

目的 探索溃疡性结肠炎中医学证型分类及分布规律.方法 病例来源于2016年11月～2019年1月北京中医药大学东方医院脾胃肝胆科门诊及住院患者.根据统计学中调查质量控制要求,编制了《溃疡性结肠炎的中医证候问卷》,严格按照临床设计方案收集患者四项诊断资料,运用因子分析及聚类分析方法对120例患者的四诊信息进行研究,以获得溃疡性结肠炎主要中医证型分类的及分布规律.结果 通过对溃疡性结肠炎患者的证候信息进行因子分析与聚类分析,得出3个主要证型:大肠湿热兼脾虚湿蕴证(54例,45％)、寒热错杂兼肝郁脾虚证(34例,28％)、肝郁脾虚兼脾阳虚证(32例,27％).结论 通过因子分析与聚类分析能够较客观地分析出溃疡性结肠炎的中医证型分类及分布规律,发现溃疡性结肠炎中医证候学特点.

国医大师柴嵩岩教授提出,高泌乳素血症病机为热毒浸淫、冲任失调.临证需辨溢乳、月经、大便、头窍之症状.治法以清热解毒、益肾调经.用药以清热解毒、消肿散结之品为主,配伍滋阴、疏肝、通便之品.

中医对“脑”的认识十分超前,早在殷商时期就对脑的功能有了初步判断.随着历史的推进,中医对“脑”范畴的理解也不断发展.自《黄帝内经》成书后,中医“脑”范畴基本确立,之后有关“脑”的内容逐渐丰富.本文从历史角度入手,探讨唐以前各阶段社会背景对“脑”范畴的影响,以及唐以前中医“脑”范畴的流变过程.