The hepatic steatosis index (HSI) is a practical indicator for screening fatty liver disease. This research aimed to evaluate the relationship between HSI and gallstones. This cross-sectional population-based investigation utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 2017 to 2020. Gallstones were defined as a self-reported history of physician-diagnosed gallstones. We systematically examined the relationship between HSI and gallstones using multivariable logistic regression models that accounted for survey weighting, with stratified analyses conducted to test the consistency of the link across diverse demographic groups. This study comprised 6368 participants above 20 years old, 680 of whom had gallstones. A positive association was observed between HSI and gallstones. Following comprehensive adjustment for potential confounding variables, each unit increase in HSI was linked to a 5% rise in prevalence of gallstones (odds ratio = 1.05, 95% confidence interval = 1.04-1.07). Categorizing HSIs into quartiles, it was observed that participants in the top HSI quartile exhibited a significantly higher prevalence of gallstones relative to those in the bottom quartile (odds ratio = 3.78, 95% confidence interval = 2.60-5.50). Stratified analyses further confirmed that this association stayed statistically significant across most subgroups. In this cross-sectional study, higher HSI levels were associated with a higher prevalence of gallstones. However, longitudinal studies are needed to confirm these findings and clarify the underlying mechanisms.

BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by intrahepatic accumulation and is closely associated with metabolic problems. Some studies have indicated that Chaihu-Shugan-San (CSS) may have a positive effect on NAFLD, but robust evidence-based research to substantiate the application of CSS is scarce. A meta-analysis was conducted to assess the clinical efficacy and safety of CSS in the treatment for NAFLD. METHODS:The literature reporting CSS in NAFLD was searched from inception to October 2023 in in 7 Chinese or English databases. Studies were screened and incorporated based on predefined criteria. Data were extracted and quality was assessed independently by 2 researchers according to the Cochrane risk of bias tools. The changes in outcomes were analyzed using the mean difference (MD) and 95% confidence intervals (CIs) with a random- or fixed-effects model to examine the effect of CSS. RevMan5.4 software was used to perform meta-analyses, and the meta package of R 4.0.0 software was used for publication bias analysis. RESULTS:A total 17 studies involving 1576 participants were screened for meta-analysis. There was high heterogeneity among studies for all continuous outcomes. Compared with common treatments, CSS could decrease aspartate-aminotransferase (MD = -12.02, 95% CI [-15.97, -8.07]), alanine-aminotransferase (MD = -10.89, 95% CI [-16.35, -5.43]), triglyceride and total cholesterol levels. In addition, CSS may increase the high-density lipoprotein cholesterol levels. And, CSS was associated with a lower incidence of adverse events (RR = 0.79, 95% CI [0.33, 1.91]). CONCLUSION:Current evidence shows that single or combined use of CSS is effective for NAFLD liver enzymes and blood lipids. Nevertheless, it is challenging to reach a conclusive determination owing to significant heterogeneity and ambiguous risk of bias in some trials. Therefore, more high-quality evidence is required for the clinical implementation of CSS.

Abstract Background The most common progressive form of non-alcoholic fatty liver disease (NAFLD) is non-alcoholic steatohepatitis (NASH), which is characterized by the development of cirrhosis, and requires liver transplantation. We screened for the differentially expressed necroptosis-related genes in NASH in this study, and analyzed immune infiltration through microarray and bioinformatics analysis to identify potential biomarkers, and explore the molecular mechanisms involved in NASH. Methods The GSE24807 microarray dataset of NASH patients and healthy controls was downloaded, and we identified the differentially expressed genes (DEGs). Necroptosis-related differential genes (NRDEGs) were extracted from these DEGs, and functionally annotated by enrichment analyses. The core genes were obtained by constructing gene co-expression networks using weighted gene co-expression network analysis (WGCNA). Finally, the transcription factor (TF) regulatory network and the mRNA-miRNA network were constructed, and the infiltrating immune cell populations were analyzed with CIBERSORT. Results We identified six necroptosis-related genes (CASP1, GLUL, PYCARD, IL33, SHARPIN, and IRF9), and they are potential diagnostic biomarkers for NASH. In particular, PYCARD is a potential biomarker for NAFLD progression. Analyses of immune infiltration showed that M2 macrophages, γδ T cells, and T follicular helper cells were associated with the immune microenvironment of NASH, which is possibly regulated by CASP1, IL33, and IRF9. Conclusions We identified six necroptosis-related genes in NASH, which are also potential diagnostic biomarkers. Our study provides new insights into the molecular mechanisms and immune microenvironment of NASH.

"治肝实脾"是根据中医五行理论确定的治疗肝病的重要治法,是五脏一体观的重要体现."治肝实脾"即通过"实脾"以治疗肝病,从而达到脾胃健、肝病愈的最佳治疗效果,在肝病的治疗中应用广泛,成为治疗肝病的重要法则.酒精性肝纤维化(ALF)归属于中医"酒癖"范畴,中医认为本病病位主要在肝、脾,湿热酒毒为致病之因,脾胃虚弱为发病之本,且贯穿于疾病始终,病机的关键为脾胃受损、肝脾不和.中医历来重视整体观,本文基于"治肝实脾"理论浅谈"实脾"在酒癖治疗过程中的重要作用,以期为酒癖的治疗提供新的思路,提高临床疗效.

现代社会,随着生活水平的提高以及社会压力的增大,酒精消耗量日益增多,酒精性肝纤维化(ALF)的发病率呈上升趋势.ALF是酒精性肝病发展过程中的关键阶段,具有可逆性,延缓甚至逆转ALF进程是治疗酒精性肝病的重点.西医学治疗方案有限,疗效不甚满意.近年来中医对本病病因病机、理法方药研究不断深入,中医药论治ALF的体系日益完善,其治疗具有多层次、多环节、多靶点的特点.基于ALF病因病机特点,探讨临床选方用药思路及特点,以期提高中医药治疗本病的临床疗效.

Immune-related genes (IRGs) have attracted attention in recent years as therapeutic targets in various tumors. However, the role of IRGs in gastric cancer (GC) has not been clearly elucidated. This study presents a comprehensive analysis exploring the clinical, molecular, immune, and drug response features characterizing the IRGs in GC. Data were acquired from the TCGA and GEO databases. The Cox regression analyses were performed to develop a prognostic risk signature. The genetic variants, immune infiltration, and drug responses associated with the risk signature were explored using bioinformatics methods. Lastly, the expression of the IRS was verified by qRT-PCR in cell lines. In this manner, an immune-related signature (IRS) was established based on 8 IRGs. According to the IRS, patients were divided into the low-risk group (LRG) and high-risk group (HRG). Compared with the HRG, the LRG was characterized by a better prognosis, high genomic instability, more CD8+ T cell infiltration, greater sensitivity to chemotherapeutic drugs, and greater likelihood of benefiting from the immunotherapy. Moreover, the expression result showed good consistency between the qRT-PCR and TCGA cohort. Our findings provide insights into the specific clinical and immune features underlying the IRS, which may be important for patient treatment.

细胞焦亡是近年来新发现的一种有别于细胞坏死、凋亡、自噬的细胞程序性死亡的新形式.酒精性肝病(ALD)是长期饮酒过量导致慢性酒精中毒的主要表现之一.目前研究证实细胞焦亡涉及ALD的发病机制为酒精诱导的肝细胞炎症小体通路激活促进肝细胞的焦亡.此机制与中医"痰瘀毒"导致ALD的发病机制有其相似之处.因此,从"痰瘀毒"病机探讨细胞焦亡在ALD中的发病分子机制,有望为ALD的治疗提供新的临床指导原则.

Alcoholic liver disease (ALD) often leads to hepatitis, hepatic cirrhosis, and even hepatocellular carcinoma. Fisetin has been shown to confer protection against liver injury. Herein, we investigated whether fisetin could prevent ethanol-induced hepatotoxicity. Mice were fed on 5% (v/v) Lieber-DeCarli ethanol diet. Human primary hepatic stellate cells (HSCs) co-cultured with ethanol were used to verify the therapeutic effect of fisetin. The results of alanine/aspartate aminotransferase (ALT/AST), Triglyceride (TG), total cholesterol (TC) in serum, Oil O Red and Masson staining revealed that fisetin (80[Formula: see text]mg/kg) ameliorated ethanol-induced mice liver injury and fibrosis. Besides, immunofluorescence results of [Formula: see text]-SMA revealed that fisetin suppressed HSCs activation. The suppression was dose-dependent. Furthermore, fisetin promoted SIRT1-mediated autophagy and inhibited Sphk1-mediated endoplasmic reticulum stress (ER stress) both in vitro and in vivo. Molecular docking results indicated potential interaction of fisetin with SIRT1 and SphK1. The inhibitory effect of fisetin on HSCs activation was reversed on co-culturing with EX-527, a specific inhibitor against STIR1 overexpression. Thus, fisetin has the potential to ameliorate alcohol-induced liver injury through suppression of HSCs activation, SIRT1-mediated autophagy and Sphk1-mediated ER stress.

胃食管反流病是消化系统常见的慢性、复发性疾病,部分患者经规范治疗后症状不能缓解,或长期反复发作,影响生活质量.本文尝试以圆运动理论为基础,再探胃食管反流病的病机特点与辨治,认为中轴运转正常,四维升降有序,人既安和,若轴不旋转,或四维升降失常,中轴运转停滞,胃气上逆,上犯食管而发为本病,治疗以"运轴以复轮"或"轴轮并运"为法,使中轴运转正常,四维升降复旧,人身气机运动之圆恢复,则疾病向愈,以期为胃食管反流病的临床治疗提供新的思路.

基于气血津液对便秘进行辨证,首辨气血津液,次辨虚实,结合临床不同群体的体质特点,根据兼证辨别所涉及脏腑及病理因素,全面把握,准确辨证,辅以润肠通便药,以取得满意疗效.

酒精性肝纤维化是长期过量饮酒,肝细胞受乙醇及其代谢产物持续性损伤出现变性坏死或损伤后修复过程中的代偿反应,细胞外基质大量沉积于肝脏为其主要病理特征[1,2 ].据统计,中国酒精性肝病(ALD)人数正以惊人的速度上升,非病毒性肝炎肝硬化患者中ALD所占比例最高,已成为我国最主要的慢性肝病之一[3,4].酒精性肝纤维化是进展为肝硬化、肝癌的必然阶段,临床与实验研究发现,其具有可逆转性,早期干预对阻断病情发展及延缓病程有十分重要的意义[5,6].

[目的]从多角度总结胆腑和肾脏的内在联系,以期为临床胆病治肾、肾病治胆提供理论依据.[方法]通过查阅中医经典书籍及相关文献,从经络、五行、生理病理、现代研究探讨等方面详细阐述胆和肾的内在联系.[结果]经络相关方面,带脉、三焦经、京门穴、风池穴、悬颅穴为胆肾联系的枢纽;五行相关方面,胆肾五行属母子关系;生理功能方面,胆肾共同主骨、共司相火、布散真精、藏泄互用、共调水液、共调阴阳、共调情志;病理方面,胆肾相互影响.中医临床研究证实胆病治肾、肾病治胆的可行性;现代研究也发现胆和肾在病理生理方面的内在联系.[结论]胆腑和肾脏生理上相互配合、病理上相互影响具有扎实的中医古代理论基础,明晰二者的内在联系为胆病治肾、肾病治胆提供方向、扩展思路,可有效提高临床疗效,值得临床借鉴.

泄泻是指大便次数增多,粪质稀薄,甚至泻出如水样为主要症状的疾病.本文从风、湿、气、虚四个环节论述泄泻病机,治疗上注重调肝理肺,以期通过调节气机升降,使脾胃功能正常运行.基于圆运动理论,使人身之气从病态循行恢复到常态运行,以达到轮运复轴的作用.从而为临床治疗泄泻提供新的治疗思路.

目的:通过网络药理学的方法,探讨茵陈蒿汤治疗肝纤维化可能的药理作用机制.方法:通过TCMSP数据库获取茵陈蒿汤主要活性成分,通过SwissTargetPrediction平台进行成分靶标预测;经Gene-Cards、OMIM和DisGeNET数据库获取肝纤维化相关靶点,与中药成分靶点取交集,获得茵陈蒿汤治疗肝纤维化的潜在作用靶点;应用Cytoscape软件构建中药-活性成分-交集靶点网络图,使用String数据库进行蛋白质相互作用(PPI)网络分析,依据度中心 性大小筛选关键靶点;通过DAVID平台对关键靶点进行GO和KEGG富集分析,以探究茵陈蒿汤治疗肝纤维化的药理作用机制.结果:筛选出茵陈蒿汤活性成分44个,包括槲皮素、β谷甾醇、异鼠李素等核心成分;茵陈蒿治疗肝纤维化的潜在作用靶点174个;对交集靶点进行蛋白质互相作用网络分析获取关键靶点63个,包括MAPK1、PIK3CA、SRC、PIK3R1、MAPK3、AKT1等核心靶点;关键靶点基因的GO及KEGG富集分析显示:关键靶标主要在细胞核、细胞质、胞浆、质膜及核质等位置发挥作用,通过信号传导、凋亡过程负调节、细胞增殖正调节及RNA聚合酶Ⅱ启动子转录的正调控等生物过程,发挥与蛋白质结合、ATP结合、蛋白激酶活性及蛋白酪氨酸激酶活性等功能.关键靶点主要通过参与PI3K-Akt信号通路、Ras信号通路、VEGF信号通路等对肝纤维化进行调控.结论:茵陈蒿汤中槲皮素、β谷甾醇、异鼠李素等核心成分,可能通过参与PI3K-Akt、Ras、VEGF等信号通路,作用于MAPK1、PIK3CA、SRC等基因靶点,发挥抗纤维化作用.

近年来我国酒精性肝病(ALD)的发病率正以惊人的速度上升,已经成为国内外学者研究的焦点问题之一.不少研究表明习惯性长期饮酒会引起肠道菌群失调,已经证实肠道菌群失调在肝脏疾病发生、发展中的核心作用.以改善肠道微生态失衡为切入点的治疗有望成为ALD新的治疗契机.“调肝理脾”法治疗ALD在长期临床实践及前期研究中被证实可有效解除酒精对肝脏的损伤,保护肝细胞,减轻肝纤维化程度,但作用机制尚未被完全阐明.因此,本文从肠道微生态角度系统阐述了“调肝理脾”法治疗ALD的现代理论学基础,并在前期研究基础上,探索“调肝理脾”法治疗ALD的效应机制,以期找到治疗ALD新的思路和研究方向.

目的:利用食管癌的可变剪切数据,构建食管癌预后风险模型并建立列线图.方法:分别从癌症基因图谱(The Cancer Genome Atlas.TCGA)SpliceSeq数据库和TCGA数据库下载食管癌的可变剪切数据和食管癌患者的临床资料,将2个数据集合并,得到食管癌可变剪切的生存数据.采用单因素COX回归分析筛选与预后相关的可变剪切,为避免模型过度拟合,采用最小绝对值收敛和选择算子(least absolute shrinkage and selection operator,LASSO)回归分析筛选变量;随后将筛选得到的可变剪切纳入多因素COZ回归分析构建食管癌的预后风险模型.基于该模型计算每位患者的风险评分并根据风险评分的中位数将患者分为高风险组和低风险组,采用Kaplan-Meie进行生存分析和受试者接受特征(receiver operating characteristic,ROC)曲线对模型效能进行评价.最终将风险模型与临床病理特征合并,采用CO义回归分析探究食管癌的独立预后因素并建立列线图.采用一致性指数(concordance index,C-index),校准图和决策曲线来评价列线图的预测准确度.结果:从TCGA SpliceSeq和TCGA数据库下载得到185例食管癌患者的可变剪切数据和临床资料.采用单因素COX回归分析筛选得到2 389个与食管癌预后相关的可变剪切,随后采用Lasso回归分析筛选得到17个可变剪切,使用多因素COX回归分析建立了基于10个基因CCHRDL2、ERBB2、IAH1,C16orf13、C19orf82、 RNF150、PNKP、ZNF467、TMWRSS4和HPS1)的可变剪切的食管癌预后风险模型.基于模型风险评分,将样本分为高风险组和低风险组;Kaplan-Meier生存分析显示,高风险组的总生存(overall survival,OS)率较低风险组差(P<0.05),ROC分析结果提示,该食管癌预后风险模型预测性良好[曲线下面积(area under curve,AUC)= 0.865％ COX回归分析结果显示,病理分期和风险评分是食管癌的独立预后因子.结合这些预后因子构建的列线图显示出较好的区分度(C-index为0.79;95％可信区间为0.752?0.843),校准曲线及决策曲线提示该列线图具有较好的预测食管癌患者OS期的能力.结论:基于可变剪切的预后风险模型能够明显区分高风险和低风险组食管癌患者的生存率.基于模型风险评分及病理分期构建的列线图能够有效地预测食管癌患者的OS率.

基于“因虚致郁”理论探讨功能性消化不良的中医诊治思路.认为功能性消化不良以脾胃虚弱为发病之本,“因虚致部”为病机之要,气郁导致痰湿阻络为病机变化的转折点,痰气郁阻、瘀血阻络终致疾病迁延不愈.临证时紧扣“因虚致郁”,重发病之源,遣方用药时以平补脾胃为先,清化湿浊、通降行气、缓消瘀积为用;晓治病之则,扶正以祛邪,祛邪而不伤正.

非酒精性脂肪肝(NAFLD)是一种代谢综合征在肝脏的表现,其发病机制复杂.近年来相关的研究发现肠道菌群参与NAFLD的疾病过程.肠道菌群紊乱和肠道通透性增加导致肠道内细菌和内毒素通过门静脉系统进入肝脏,加剧了NAFLD的发展.目前,传统中医药治疗NAFLD的疗效受到认可.中药在胃肠道中与肠道菌群相互作用,通过影响菌群的生理功能、免疫调节、菌群代谢等对肠道菌群进行调节,使肠道微生态趋于平衡,减少细菌易位和内毒素的增加,从而减轻NAFLD的程度,这可能是中药防治NAFLD新的作用机制.

BACKGROUND:Alcoholic liver disease (ALD) is one of the major cause of morbidity and mortality of clinical liver disease worldwide. Until today, although many general therapies are carried out and several molecular targets have been proposed to act as the potential therapeutic targets, more accurate molecular targets and more effective therapeutic methods remain needed.MATERIAL AND METHODS:In the study, we analyze the differential expression genes (DEGs) between the patients with ALD and healthy controls. Gene Ontology enrichment and KEGG signaling pathway analysis are performed to identify the function of DEGs. Some significant molecules are proposed to act as the potential therapeutic targets for ALD. RNA data of 15 ALD tissues and 7 normal tissues for RNA expression analysis were obtained. DEGs in ALD samples compared with normal tissues identified through the limma R package and subjected to network analysis.RESULTS:As a result, we obtained a total of 274 DEGs that mainly involved in biological processes related to the angiogenesis, stress reaction, synthesis, and metabolism of organic acids. Network analysis obtained several genes with high network degree and fold change. Some significant molecules are proposed to act as the potential therapeutic targets for ALD.CONCLUSIONS:Our research identified some new progression-related genes of alcohol liver diseases, which could be regarded as the new targets for the early diagnosis and therapeutic management in ALD.