BACKGROUND:Studies have shown that advanced liver fibrosis is strongly associated with cardiovascular risk factors (including age and smoking status). Nevertheless, the exact mechanism is not yet clear. Hence, this study aimed to investigate the relationship between coronary heart disease (CHD) and advanced liver fibrosis and to reveal the developmental processes. METHODS:In this study, we included 9254 participant data from the National Health and Nutrition Examination Surveydatabases in 2017-2018 to explore the association between risk factors and advanced liver fibrosis. First, the baseline characteristics of the participants were examined using Student's t -test and chi-squared test. Moreover, the association between CHD and advanced liver fibrosis was assessed using logistic regression analysis. Thereafter, the receiver operating characteristic curve was used to further evaluate the diagnostic performance of model 3 for advanced liver fibrosis. RESULTS:In total, 3624 participants were included in this study after removing samples with missing information. Baseline statistics showed that CHD, age, sex, BMI, alcohol consumption, smoking, diabetes, and physical activity were all remarkably discrepancies between nonadvanced and advanced liver fibrosis groups ( P  < 0.05). Of these, CHD was shown to have a strong association with advanced liver fibrosis (95% confidence interval (CI), 1.84-7.27, P  = 0.0063, odds ratio (OR) = 3.6587). Moreover, the effect of CHD on advanced liver fibrosis was not confounded by other confounders in model 3, in which confounders were corrected. Eventually, with an area under the curve greater than 0.7, the receiver operating characteristic curve confirmed the good diagnostic performance of Model 3 for advanced liver fibrosis. CONCLUSION:This study suggested that having CHD was a risk factor for patients with advanced liver fibrosis, which provides a basis for the study of advanced liver fibrosis.

Introduction Hepatic encephalopathy (HE) is a major complication of acute liver failure, cirrhosis and transjugular intrahepatic portosystemic shunt (TIPS) placement. Its clinical manifestations range from mild cognitive deficits to coma. Furthermore, HE is a financial burden to a patient’s family and significantly affects the patient’s quality of life. In clinical practice, proton pump inhibitors (PPIs) are widely used for the treatment of HE. The use of PPIs is associated with an increased risk of post-TIPS HE; however, findings on the risk relationship between PPIs and post-TIPS HE are inconsistent. Therefore, a systematic evaluation of the relationship is needed to further provide valid evidence for the rational use of PPIs in patients who undergo TIPS.Methods and analysis PubMed, Web of Science, Cochrane Library and Embase will be searched extensively for relevant information. Information from 1 July 2023 to 31 July 2023 in these databases will be included. Primary outcomes will be the use of PPIs and incidence of HE after TIPS; secondary outcomes will be survival, dose dependence and adverse events. This meta-analysis will be reported in accordance with the 50 Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. The risk of bias, heterogeneity and quality of evidence of the included studies will be evaluated prior to the data analysis. All data will be analysed using Review Manager (V.5.4.1) and Stata (V.17.0) statistical software.Ethics and dissemination Ethical approval will not be necessary for this review and meta-analysis. The results of the study will be published in a peer-reviewed journal.PROSPERO registration number CRD42022359208.

BACKGROUND AND AIM:Currently, hepatitis B virus-related acute liver failure (HBV-ALF) has limited treatment options. Studies have shown that histone lactylation plays a role in the progression of liver-related diseases. Therefore, it is essential to explore lactylation-related gene (LRGs) biomarkers in HBV-ALF to provide new information for the treatment of HBV-ALF. METHODS:Two HBV-ALF-related datasets (GSE38941 and GSE14668) and 65 LRGs were used. First, the differentially expressed genes (DEGs) were derived from differential expression analysis, the key module genes from weighted gene co-expression network analysis; and LRGs were used to intersect to obtain the candidate genes. Subsequently, the feature genes obtained from least absolute shrinkage and selection operator regression analysis and support vector machine analysis were intersected to obtain the candidate key genes. Among them, genes with consistent and significant expression trends in both GSE38941 and GSE14668 were used as biomarkers. Subsequently, biomarkers were analyzed for functional enrichment, immune infiltration, and sensitive drug prediction. RESULTS:In this study, five candidate genes (PIGM, PIGA, EGR1, PIGK, and PIGL) were identified by intersecting 6461 DEGs and 2496 key module genes with 65 LRGs. We then screened four candidate key genes from the machine learning algorithm, among which PIGM and PIGA were considered biomarkers in HBV-ALF. Moreover, the results of enrichment analysis showed that the significant enrichment signaling pathways for biomarkers included allograft rejection and valine, leucine, and isoleucine degradation. Thereafter, 11 immune cells differed significantly between groups, with resting memory CD4+ T cells having the strongest positive correlation with biomarkers. Methylphenidate hydrochloride is a potential therapeutic drug for PIGM. CONCLUSION:Two genes, PIGM and PIGA, were identified as biomarkers related to LRGs in HBV-ALF, providing a basis for understanding HBV-ALF pathogenesis.

通腑开窍法中药保留灌肠在肝性脑病中的应用疗效显著,本文通过归纳总结近20年通腑开窍法中药保留灌肠在肝性脑病中的应用及临床疗效,为通腑开窍法在肝性脑病中的研究与应用提供参考,从而提高肝性脑病的防治水平,改善生活质量并减轻经济负担.同时,本文涉及目前通腑开窍法中药保留灌肠存在的问题,规范肝性脑病通腑开窍法中药保留灌肠在临床的运用,以期让传统的中医中药发挥优势,从而解决临床问题.

基于肝-大肠-脑相通理论,探讨大黄煎剂治疗肝性脑病的机制,以及煎药剂量、时间、温度的选择,灌肠时间、方式、药物加减的选择,为临床工作提供参考.

INTRODUCTION:The prevalence of chronic kidney disease (CKD) rises with age and co-morbid diseases such as liver diseases.OBJECTIVES:The main aim of the current meta-analysis is to assess the relationship between Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease incidence in both diabetic and non-diabetic subjects compared with control.MATERIAL AND METHODS:A systematic literature search of papers published from January 1, 2005, till April 30, 2022, found 19 studies including 1,111,046 subjects; 310,804 were diagnosed with NAFLD, and 800,242 were non-NAFLD. The measured outcome was the incidence of CKD among NAFLD subjects compared to non-NAFLD subjects in diabetic and non-diabetic subjects. Dichotomous analysis methods were used within the random effects model to calculate the odds ratio (OR) with 95% confidence intervals (95% CIs).RESULTS:The incidence of CKD is highly significant in NAFLD subjects compared with controls (OR: 1.95; 95% CI: 1.65-2.31). The diabetic non-NAFLD subjects showed a significantly increased incidence of CKD compared to the non-diabetic subjects with NAFLD (OR: 1.79; 95% CI: 1.35-2.38).. In addition, the incidence of CKD was significantly higher in the NAFLD group compared with the non-NAFLD non-diabetic subjects (OR: 2.52; 95% CI: 1.91-3.32). Diabetes acts as an independent risk factor for CKD, as proven by a significant increase in incidence of diabetic subjects compared to non-diabetic NAFLD subjects (OR: 1.82; 95% CI: 1.15-2.88).CONCLUSION:Non-alcoholic fatty liver disease is significantly related to an increased incidence of CKD, which is significantly higher in diabetic subjects.

本文综述了非酒精性单纯性脂肪肝(Non-alcoholic simple fatty liver,NAFL)的发病机制及中医防治方面的研究进展.非酒精性单纯性脂肪肝(NAFL)——非酒精性脂肪肝(Non-alcoholic fatty liver diseases,NAFLD)初期阶段,主要特征为脂肪贮积及肝脏脂肪变性.NAFL患者一般无明显症状,在组织学上以肝细胞脂肪变性为主.目前我国对NAFL已有统一的西医诊断标准,但中医诊断标准尚未统一,中医辨证论治参考《非酒精性脂肪性肝病的中西医结合诊疗共识意见》NAFLD的辨证标准.由于NAFL的发病机制较为复杂,临床治疗尚无特效药,常用药物单一且疗效不佳.相比之下,中医药在NAFL的防治上有独特的见解与优势,不良反应少,疗效显著,值得推广.

Background: The Qingjiehuagong decoction (QJHGD), which has been used in clinical trials to treat acute pancreatitis (AP), has demonstrated encouraging results. Methods: In this particular investigation, we used both metabolomics and network pharmacology to investigate the fundamental processes and targets that QJHGFD employs to cure AP. Results: Using a cerulein-induced rat model of AP, we showed that QJHGD effectively improved pancreatic tissue damage and reduced serum levels of AMY, LPS, IL-1β, IL-6, IL-8 and TNF-α. In total, 28 blood entry compounds derived from QJHGD were identified by ultra-performance liquid chromatography-high resolution mass spectrometry technology. The intersecting target genes of 108 genes associated with identified compounds in QJHGD and AP disease genes were identified using a network pharmacology approach. The protein interaction network revealed AKT1, TNF-α, IL-6, VEGFA, and TP53 as important targets. Gene ontology analysis showed that response to stimulus, molecular function regulator and organelle part were the main functions, and Kyoto Encyclopedia of Genes and Genomes analysis showed that 20 pathways such as AGE-RAGE signaling pathway in diabetic complications and the IL-17 signaling pathway were the main pathways involved in the anti-AP effects of QJHGD. Thirty-two potential metabolic markers and 13 possible metabolic pathways were identified by metabolomics analysis. Combined network pharmacological analysis revealed that QJHGD affects four metabolic pathways (tryptophan metabolism; glycolysis and gluconeogenesis metabolism; valine, leucine and isoleucine degradation metabolism; the urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine), five metabolites (indole-3-acetate, pyruvate, methylmalonate, L-citrulline, N-acetyl-l-glutamate) and four related targets (AKT1, ALDH2, NOS2, NOS3) to combat inflammation. The strong affinity of QJHGD’s interactions with its primary targets was established by molecular docking and molecular dynamics simulations. Conclusion: This research investigate the critical targets and mechanisms of QJHGFD for treating AP. The results of this investigation provide novel tactics and complementary techniques for the clinical treatment of AP.

Objective To explore the mechanism of the acupuncture therapy at peri-jiaji acupoints on arterial blood flow velocity of upper limb in treating patients with post-stroke upper-limb spasticity. Methods A total of110 patients with post-stroke upper-limb spasticity were randomly divided into the observation group and the control group,with 55 cases in each group. The control group was treated with Bobath therapy and the observation group was treated with acupuncture therapy at peri-jiaji acupoints combined with Bobath therapy. Both groups of patients were treated for a period of 8 weeks. The pre-and post-treatment changes in the modified Ashworth spasticity classification,clinical spasticity index（CSI）scores,modified Barthel index（MBI）scores,upper limb arterial blood flow velocity and serum levels of nerve growth factor（NGF）and calcium binding protein S100β（S100β）in the two groups were observed. After treatment,the clinical efficacy of the two groups was evaluated.Results（1）After 8 weeks of treatment,the overall effective rate of the observation group was 96.36%（53/55）and that of the control group was 76.36%（42/55）, and the intergroup comparison showed that the efficacy of the observation group was significantly superior to that of the control group（P＜0.01）.（2）After treatment, the modified Ashworth spasticity classification of patients in both groups was significantly improved compared with that before treatment（P＜0.05）,and the improvement in the observation group was significantly superior to that in the control group（P＜0.01）.（3）The peak systolic velocity（PSV）values of blood flow of the radial and brachial arteries were significantly increased in the observation group after 2,4 and 8 weeks of treatment and in the control group after 4 and 8 weeks of treatment compared with those before treatment（P＜0.05）,and the increase of the PSV values of the radial and brachial arteries in the observation group was significantly superior to that in the control group after 2, 4 and 8 weeks of treatment（P＜0.01）.（4）The serum NGF and S100β levels in the observation group after 2,4 and 8 weeks of treatment and in the control group after 4 and 8 weeks of treatment were significantly decreased compared with those before treatment（P＜0.05）,and the decrease of serum NGF and S100β levels in the observation group after 2,4 and 8 weeks of treatment was significantly superior to that in the control group（P＜0.01）.（5）The CSI scores in the observation group after 2,4 and 8 weeks of treatment and in the control group after 4 and 8 weeks of treatment were significantly decreased（P＜0.05）and the MBI scores in both groups were significantly increased（P＜0.05）in comparison with those before treatment,and the degree of reduction in CSI scores and the degree of increase in MBI scores in the observation group after 2,4 and 8 weeks of treatment were significantly superior to those in the control group（P＜0.01）. Conclusion The acupuncture therapy at peri-jiaji acupoints can effectively improve the blood flow velocity of upper limb arteries as well as self-care ability and the degree of spasticity,and decrease the serum NGF and S100β levels in patients with post-stroke upper-limb spasticity.

目的 运用UHPLC-QTOF-MS和网络药理学探讨温阳化浊退黄方治疗慢加急性肝衰竭(Acute-on-chronic liver failure,ACLF)的作用机制,并通过实验验证筛选出的靶点.方法 利用UHPLC-QTOF-MS分析温阳化浊退黄方的活性成分,利用网络药理学方法 筛选温阳化浊退黄方活性成分对应的靶点和ACLF靶点,构建蛋白互作网络(PPI)筛选核心靶点,对靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路分析,利用Cytoscape构建活性成分-靶点-通路网络图,通过动物模型实验验证温阳化浊退黄方治疗ACLF的作用机制.结果 UHPLC-QTOF-MS共鉴定出123个化合物,经TCMSP筛选得到12种活性成分,TCMSP和Swiss target Prediction数据库取交集共获得181个温阳化浊退黄方预测靶点;得到ACLF靶点2019个;温阳化浊退黄方和ACLF共有靶点99个.KEGG通路分析筛选了147条相关信号通路,显示PI3K/Akt信号通路、VEGF信号通路、乙型肝炎、细胞凋亡、MAPK信号通路等可能在温阳化浊退黄方治疗ACLF的过程中起关键作用.动物实验结果 显示,温阳化浊退黄方能够缓解ACLF大鼠肝损伤,下调AKT1、MTOR和RAF1关键靶蛋白在ACLF大鼠肝脏中的表达,验证了网络药理学的预测结果 .结论 温阳化浊退黄方通过多成分、多靶点、多通路协同作用治疗ACLF,为后续研究提供参考依据.

目前肝病的发病率仍较高,严重威胁民众健康,寻找多途径治疗慢性肝病是临床的迫切需求.壮药是颇具民族特色的传统药物,在治疗肝病方面具有一定的优势.本文对壮医药治疗肝病的机制进行综述,以期为深入研究壮医药在治疗肝病中的作用提供参考.

慢性乙型病毒性肝炎(CHB)是一类传染性强、流传范围广的慢性传染病,其主要病因是感染乙肝病毒.目前单纯运用西医治疗该病存在疗程长,有耐药风险,临床症状未能妥善处理等阻碍,同时CHB疾病不及时治疗或治疗不当,发展成为相关性肝硬化、原发性肝癌、肝衰竭的风险将增加.通过查阅文献发现,辨证运用疏肝健脾法结合抗病毒疗法治疗肝郁脾虚型CHB能够明显改善患者临床症状、肝功能指标,延缓肝纤维化进程.文章从疏肝健脾法结合抗病毒治疗的理论依据、临床疗效等方面进行综述,以期为CHB的临床治疗提供帮助.

目的 系统评价中药多途径治疗急性胰腺炎并发腹间隔室综合征疗效。方法 检索中国知网、万方、维普、Sinomed、PubMed、Embase、Cochrane Library自建库至2020年12月1日收录的中医药治疗急性胰腺炎并发腹间隔室综合征的临床试验，RevMan5.3软件进行荟萃分析。结果 共纳入17项研究，共1 033例病人；荟萃分析显示，与西药基础治疗比较，中西药联用可显著降低腹内压[标准化均数差（SMD）95%CI：-0.63（-0.83,0.43）]；与西药基础治疗比较，联用中药组可显著降低急性生理学和慢性健康状况评价Ⅱ（APACHE Ⅱ）评分[SMD 95%CI：-0.65（-0.87,0.43）]；与西药基础治疗比较，联用中药组可有效缩短排便恢复时间[SMD 95%CI：-0.68（-1.14,0.22）]；此外，小样本的研究表明中西医结合相较于单纯西药治疗可降低病人死亡情况[比值比（OR）95%CI:1.04（-1.91，-0.16）]。结论 中药治疗急性胰腺炎并发腹间隔室综合征可降低腹内压、减少临床APACHE Ⅱ评分、缩短病人排便恢复时间。

目的 基于数据整合研究(处方挖掘、网络药理学、分子对接及动力学模拟)探讨陈国忠治疗慢性萎缩性胃炎(chronic atrophic gastritis,CAG)组方规律、作用靶点和潜在机制.方法 基于门诊电子病历系统建立"慢性萎缩性胃炎处方用药"数据库,以频数统计、关联分析、系统聚类探讨处方核心药团和聚类新方;网络药理学分析构建药物-成分-靶点网络图,对核心基因富集分析;分子对接及动力学模拟验证核心药靶结合的稳定性.结果 纳入129张处方,162味中药,用药寒温并用、辛开苦降,多入肺脾胃经;核心药团为黄芩、半夏、甘草,聚类为类小柴胡汤等5种新方.核心药团共98个活性成分,作用的54个主要靶点富集到脂多糖反应、PI3K-Akt等1904个生物过程与319条信号通路.核心药团主要成分槲皮素、黄芩素、豆甾醇与关键靶点PTGS2经分子对接及动力学分析显示均稳定结合.结论 陈国忠治疗慢性萎缩性胃炎用药辛苦、寒温并举,善用黄芩、半夏、甘草与柴胡等组成类小柴胡汤,治疗少阳阳明不利证;并拟三白汤诸方健脾温阳降逆、行气利湿除痞.核心药团主要成分与PTGS2等关键靶点稳定结合,多途径协同调控胃黏膜增殖、凋亡等相关通路发挥治疗作用.

肝衰竭是肝脏受损导致相应功能发生严重障碍或失代偿,是以凝血功能障碍、黄疸、肝肾综合征、肝性脑病、腹水等为主的一组复杂的临床综合征.目前单纯运用西医综合疗法治疗肝衰竭治疗难度高,预后较差,病死率高.因此寻求合理、有效且预后较为良好的治疗方案意义重大.研究通过查阅中外文献发现,辨证运用"扶阳培土"法结合西医综合疗法治疗肝衰竭阴阳黄治疗能够明显改善肝衰竭患者临床症状、肝功能、凝血功能、血浆内毒素及降低病死率.因此,从"扶阳培土"法结合西医综合疗法的理论依据、临床疗效等方面进行综述,以期为肝衰竭的临床治疗提供帮助.

Objective. Acute-on-chronic liver failure (ACLF) is a group of chronic liver diseases and caused by acute internal and external liver injury. Wenyang Huazhuo Tuihuang (WYHZTH) formula had a good clinical effect on promoting the resolution of jaundice. The aim of this study is to further investigate the mechanism of the WYHZTH formula in the ACLF rat model. Methods. The ACLF rat model was constructed by combining human serum albumin with LPS and D-gal. WYHZTH was used to intervene and treat. The cytokines IL-17, IL-23, IL-10, and TGF-β were detected by ELISA and fluorescence-quantitative PCR. Flow cytometry was used to detect the percentage of Th17 and Treg cells in the peripheral blood and liver tissues of each group of rats. The pathological changes in the liver tissue were detected by hematoxylin-eosin staining, immunohistochemistry, and electron microscopy. Results. Compared with the ACLF group, the WYHZTH formula and Thy significantly decreased the levels of ALT, AST, and CHE in the ACLF group. After drug intervention, apoptosis was significantly reduced. The PCNA expression decreased in the ACLF model group but increased in the WYHZTH or Thy group. Under transmission electron microscope, hepatocytes in the ACLF group showed obvious necrosis. After drug intervention, hepatocyte necrosis was reduced with most of the structure returning to normal. Conclusion. This present study demonstrated that WYHZTH formula may protect against acute-on-chronic liver failure, which may be related to the inhibition of Th17/Treg cell imbalance.

观察大黄、赤芍注射液介导JAK/STAT信号通路在急性肝衰竭大鼠中的作用及对肝再生的影响.选用60％肝切除术后+20 mg/100g D-GalN+1 μg/100 g LPS腹腔注射构建ALF大鼠模型,将造模成功的大鼠随机选取100只,按体质量随机均分为造模阳性对照组、促肝细胞生长素组、大黄、赤芍(低、中、高)剂量组.采用qPCR、Western Blot技术验证造模后24、48 h各组大鼠JAK2、JAK3、STAT3、STAT2表达.结果表明:大黄、赤芍注射液能够上调JAK2/JAK3、STAT2/STAT3蛋白表达,活化JAK/STAT信号通路,促进肝细胞再生,与对照组比较差异具有统计学意义P＜0.05;其中低剂量组的各项检测结果优于(中、高)剂量组,差异具有统计学意义,P＜0.05.大黄、赤芍注射液可改善急性肝衰竭大鼠肝功能,提高大鼠存活率,其机制可能与大黄、赤芍注射液降低炎症因子水平,活化JAK/STAT信号通路,诱导肝细胞再生有关.

外泌体作为细胞间通讯的关键介质,其携带可以转运到受体细胞的核酸、蛋白质和脂质.在肝病领域,外泌体正在成为肝脏疾病的发病机理中的关键角色,受损的肝细胞释放出大量的外泌体,促进炎症、纤维生成和血管生成的发生,这是肝脏疾病进展的关键病理生物学过程.近来相关研究表明,外泌体正在肝病领域发挥作用,特别是在分子诊断及靶向作用等方面的开发有着极大的应用前景;因此,本文着重介绍了外泌体分类、分离及相关修饰等情况,其植物源性外泌体在不涉及伦理情况下有着较大的挖掘可能性.同时探讨了外泌体在部分肝脏疾病中发挥作用的分子机制,为求应用于临床实践稍作铺垫.

目的 探讨尿液羧肽酶B激活肽(carboxypeptidase B activating peptide,CAPAP)作为急性重症胰腺炎(severe acute pancrea-titis,SAP)早期标志物的诊断价值.方法 检索PubMed、Embase、Web of Science、中国知网、万方以及维普数据库,时间为1995年1月至2021年3月.RevMan5.3制作QUADAS-2量表评估文献质量,Stata 16.0软件荟萃分析及绘制综合受试者工作特征(summary receiver operating characteristic,SROC)曲线,TSA 0.9.5.10 Beta软件试验序贯分析.结果 纳入9项研究,研究无阈值效应,CAPAP诊断SAP的灵敏度、特异度、阳性似然比(postive likelihood ratio,PLR)、阴性似然比(negative likelihood ratio,NLR)、诊断比值比(diagnostic oddsratio,DOR)分别为0.84、0.92、10、0.17、59;SROC曲线下面积为0.94;亚组分析提示,发表年份、研究区域和检测方法不是异质性来源;发表偏倚及敏感性分析提示文献存在发表偏倚;试验序贯分析提示需纳入更大的样本量验证CAPAP对SAP的诊断效能.结论 尿液CAPAP可以作为SAP诊断困难时的辅助指标,仍需多中心、大样本、前瞻性的研究予以验证.

目的:采用转录组高通量测序探讨清解化攻方抑制重症急性胰腺炎(SAP)炎症反应的可能机制.方法:雨蛙素联合脂多糖腹腔注射法复制SAP大鼠模型,观察空白组、模型组、中药组大鼠胰腺组织湿/干比重、血清淀粉酶、内毒素、IL-6、IL-8表达水平及病理组织改变情况;RNA-seq测序检测大鼠胰腺组织基因表达差异,筛选清解化攻方抑制炎症反应的核心基因、生物学功能及信号通路;Real-time PCR验证测序结果.结果:与模型组比较,中药组大鼠胰腺湿/干比重显著下降(P＜0.01);ELISA及胰腺病理结果表明中药组大鼠胰腺水肿、炎性因子释放以及胰腺炎症反应显著改善.测序表明中药组上调1 701个、下调1 602个胰腺差异基因,从而调节免疫炎症反应、趋化因子介导通路等生物过程,并下调TNF-α/NF-κB、MAPK、趋化因子等信号通路.中药组TNF-α、NF-κB p65、IKK β、p38MAPK、ERK1、IL-1 β较模型组表达显著下降,IκBα表达显著增加,与测序结果一致.结论:清解化攻方能有效抑制重症急性胰腺炎大鼠炎症反应,可能机制与调节TNF-α/NF-κB、MAPK等信号通路相关.