Magnetic resonance imaging ancillary features used in Liver Imaging Reporting and Data System:An illustrative review

Hepatocellular carcinoma (HCC) usually develops in the setting of chronic liver disease. In the adequate clinical context, both multiphasic contrast-enhanced CT and magnetic resonance imaging are non-invasive modalities that allow accurate diagnosis and staging of HCC, although the latter demonstrates greater sensitivity and specificity. Imaging criteria for HCC diagnosis rely on hemodynamic features such as hyperenhancement in the arterial phase and washout in the portal or equilibrium phase. However, imaging performance drops considerably for small (< 20 mm) nodules because their tendency to exhibit atypical enhancement patterns. In order to improve accuracy in the diagnosis and staging of HCC, particularly in cases of atypical nodules, ancillary features, i.e., imaging characteristics that modify the likelihood of HCC, have been described and incorporated into clinical reports, especially in Liver Imaging Reporting and Data System. In this paper, ancillary imaging features will be reviewed and illustrated.

Contrast-enhanced ultrasound Liver Imaging Reporting and Data System:Lights and shadows in hepatocellular carcinoma and cholangiocellular carcinoma diagnosis

BACKGROUND Contrast-enhanced ultrasound(CEUS)is considered a secondary examination compared to computed tomography(CT)and magnetic resonance imaging(MRI)in the diagnosis of hepatocellular carcinoma(HCC),due to the risk of misdiagnosing intrahepatic cholangiocarcinoma(ICC).The introduction of CEUS Liver Imaging Reporting and Data System(CEUS LI-RADS)might overcome this limitation.Even though data from the literature seems promising,its reliability in real-life context has not been well-established yet.AIM To test the accuracy of CEUS LI-RADS for correctly diagnosing HCC and ICC in cirrhosis.METHODS CEUS LI-RADS class was retrospectively assigned to 511 nodules identified in 269 patients suffering from liver cirrhosis.The diagnostic standard for all nodules was either biopsy(102 nodules)or CT/MRI(409 nodules).Common diagnostic accuracy indexes such as sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)were assessed for the following associations:CEUS LR-5 and HCC;CEUS LR-4 and 5 merged class and HCC;CEUS LR-M and ICC;and CEUS LR-3 and malignancy.The frequency of malignant lesions in CEUS LR-3 subgroups with different CEUS patterns was also determined.Inter-rater agreement for CEUS LI-RADS class assignment and for major CEUS pattern identification was evaluated.RESULTS CEUS LR-5 predicted HCC with a 67.6%sensitivity,97.7%specificity,and 99.3%PPV(P<0.001).The merging of LR-4 and 5 offered an improved 93.9%sensitivity in HCC diagnosis with a 94.3%specificity and 98.8%PPV(P<0.001).CEUS LR-M predicted ICC with a 91.3%sensitivity,96.7%specificity,and 99.6%NPV(P<0.001).CEUS LR-3 predominantly included benign lesions(only 28.8%of malignancies).In this class,the hypo-hypo pattern showed a much higher rate of malignant lesions(73.3%)than the iso-iso pattern(2.6%).Inter-rater agreement between internal raters for CEUS-LR class assignment was almost perfect(n=511,k=0.94,P<0.001),while the agreement among raters from separate centres was substantial(n=50,k=0.67,P<0.001).Agreement was stronger for arterial phase hyperenhancement(internal k=0.86,P<2.7×10-214;external k=0.8,P<0.001)than washout(internal k=0.79,P<1.6×10-202;external k=0.71,P<0.001).CONCLUSION CEUS LI-RADS is effective but can be improved by merging LR-4 and 5 to diagnose HCC and by splitting LR-3 into two subgroups to differentiate iso-iso nodules from other patterns.

Interobserver agreement for contrast-enhanced ultrasound of liver imaging reporting and data system:A systematic review and metaanalysis

BACKGROUND Hepatocellular carcinoma is the most common primary liver malignancy.From the results of previous studies,Liver Imaging Reporting and Data System(LIRADS)on contrast-enhanced ultrasound(CEUS)has shown satisfactory diagnostic value.However,a unified conclusion on the interobserver stability of this innovative ultrasound imaging has not been determined.The present metaanalysis examined the interobserver agreement of CEUS LI-RADS to provide some reference for subsequent related research.AIM To evaluate the interobserver agreement of LI-RADS on CEUS and analyze the sources of heterogeneity between studies.METHODS Relevant papers on the subject of interobserver agreement on CEUS LI-RADS published before March 1,2020 in China and other countries were analyzed.The studies were filtered,and the diagnostic criteria were evaluated.The selected references were analyzed using the“meta”and“metafor”packages of R software version 3.6.2.RESULTS Eight studies were ultimately included in the present analysis.Meta-analysis results revealed that the summary Kappa value of included studies was 0.76[95%confidence interval,0.67-0.83],which shows substantial agreement.Higgins I2 statistics also confirmed the substantial heterogeneity(I2=91.30%,95%confidence interval,85.3%-94.9%,P<0.01).Meta-regression identified the variables,including the method of patient enrollment,method of consistency testing,and patient race,which explained the substantial study heterogeneity.CONCLUSION CEUS LI-RADS demonstrated overall substantial interobserver agreement,but heterogeneous results between studies were also obvious.Further clinical investigations should consider a modified recommendation about the experimental design.

Hepatocellular carcinoma Liver Imaging Reporting and Data Systems treatment response assessment: Lessons learned and future directions

Hepatocellular carcinoma(HCC)is a leading cause of morbidity and mortality worldwide,with rising clinical and economic burden as incidence increases.There are a multitude of evolving treatment options,including locoregional therapies which can be used alone,in combination with each other,or in combination with systemic therapy.These treatment options have shown to be effective in achieving remission,controlling tumor progression,improving disease free and overall survival in patients who cannot undergo resection and providing a bridge to transplant by debulking tumor burden to downstage patients.Following locoregional therapy(LRT),it is crucial to provide treatment response assessment to guide management and liver transplant candidacy.Therefore,Liver Imaging Reporting and Data Systems(LI-RADS)Treatment Response Algorithm(TRA)was created to provide a standardized assessment of HCC following LRT.LIRADS TRA provides a step by step approach to evaluate each lesion independently for accurate tumor assessment.In this review,we provide an overview of different locoregional therapies for HCC,describe the expected post treatment imaging appearance following treatment,and review the LI-RADS TRA with guidance for its application in clinical practice.Unique to other publications,we will also review emerging literature supporting the use of LI-RADS for assessment of HCC treatment response after LRT.

Liver Imaging Reporting and Data System criteria for the diagnosis of hepatocellular carcinoma in clinical practice: A pictorial minireview

Hepatocellular carcinoma(HCC)is the sixth most common cancer.The main risk factors associated with HCC development include hepatitis B virus,hepatitis C virus,alcohol consumption,aflatoxin B1,and nonalcoholic fatty liver disease.However,hepatocarcinogenesis is a complex multistep process.Various factors lead to hepatocyte malignant transformation and HCC development.Diagnosis and surveillance of HCC can be made with the use of liver ultrasound(US)every 6 mo.However,the sensitivity of this imaging method to detect HCC in a cirrhotic liver is limited,due to the abnormal liver parenchyma.Computed tomography(CT)and magnetic resonance imaging(MRI)are considered to be most useful tools for at-risk patients or patients with inadequate US.Liver biopsy is still used for diagnosis and prognosis of HCC in specific nodules that cannot be definitely characterized as HCC by imaging.Recently the American College of Radiology designed the Liver Imaging Reporting and Data System(LI-RADS),which is a comprehensive system for standardized interpretation of CT and MRI liver examinations that was first proposed in 2011.In 2018,it was integrated into the American Association for the Study of Liver Diseases guidance statement for HCC.LI-RADS is designed to ensure high sensitivity,precise categorization,and high positive predictive value for the diagnosis of HCC and is applied to“highrisk populations”according to specific criteria.Most importantly LI-RADS criteria achieved international collaboration and consensus among liver experts around the world on the best practices for caring for patients with or at risk for HCC.

Modeling Liver Cancer and Leukemia Data Using Arcsine-Gaussian Distribution

The main objective of this paper is to discuss a general family of distributions generated from the symmetrical arcsine distribution.The considered family includes various asymmetrical and symmetrical probability distributions as special cases.A particular case of a symmetrical probability distribution from this family is the Arcsine–Gaussian distribution.Key statistical properties of this distribution including quantile,mean residual life,order statistics and moments are derived.The Arcsine–Gaussian parameters are estimated using two classical estimation methods called moments and maximum likelihood methods.A simulation study which provides asymptotic distribution of all considered point estimators,90%and 95%asymptotic confidence intervals are performed to examine the estimation efficiency of the considered methods numerically.The simulation results show that both biases and variances of the estimators tend to zero as the sample size increases,i.e.,the estimators are asymptotically consistent.Also,when the sample size increases the coverage probabilities of the confidence intervals increase to the nominal levels,while the corresponding length decrease and approach zero.Two real data sets from the medicine filed are used to illustrate the flexibility of the Arcsine–Gaussian distribution as compared with the normal,logistic,and Cauchy models.The proposed distribution is very versatile to fit real applications and can be used as a good alternative to the traditional gaussian distribution.

Survivals after liver transplantation for hepatocellular carcinoma:Granular data for a better allocation process?

To the Editor:A large international study has been recently published focusing on the combination of morphological aspects and alpha-fetoprotein(AFP)as predictors of survival in patients with hepatocellular cancer(HCC)treated with liver transplantation(LT)[1].As a matter of fact,morphology and biology represent the two sides of the same

“Astragali Radix−Salviae Miltiorrhizae Radix Et Rhizoma”herb pair in the treatment of liver cirrhosis and its pharmacological mechanisms

Objective:Liver cirrhosis is a disease that seriously damages human health.Traditional Chinese Medicine(TCM)formulae have a good therapeutic effect on cirrhosis,and the herb pair is the smallest unit in formula compatibility,which is important for improving the therapeutic effect.Therefore,identifying core herb pairs among TCM formulae is key.Methods:We mined the data of TCM formulae for the treatment of cirrhosis in the China National Intellectual Property Administration for the first time and analyzed their herb characteristics and association rules.We screened 405 patented TCM formulae,including 953 herbs.Based on frequency statistics and association rules,we determined“Astragali Radix-Salviae Miltiorrhizae Radix Et Rhizoma”as the core herb pair.Results:Six active compounds,Isorhamnetin,Formononetin,Calycosin,Cryptotanshinone,Dihydrotanshinone I,and Tanshinone II A,were screened out based on previous studies and network pharmacology.We found that SRC,TP53,HSP90AA1,MAPK3,MAPK1,and STAT3 played pivotal roles in treating cirrhosis.Interestingly,molecular docking indicated that MAPK3 might be a potential pharmacological target for cirrhosis.Conclusion:We preliminarily predicted and verified the pharmacological and molecular mechanism of“Astragali Radix-Salviae Miltiorrhizae Radix Et Rhizoma”in treating cirrhosis.This can expand the scope of TCM in the treatment of cirrhosis,guide people to use clinical formulae,and provide valuable insights for further drug discovery studies.

基于中医传承辅助平台对布鲁氏菌病肝肾亏虚证用药规律的分析

目的:分析中医治疗布鲁氏菌病肝肾亏虚证的用药规律,挖掘有效的药物组合及新处方。方法:检索相关数据库并查阅资料,收集关于布鲁氏菌病肝肾亏虚证的文献和医案,筛选治疗该病证的方剂。基于中医传承辅助平台(V2.5)建立方药特征数据库,并通过关联规则分析法、熵层次聚类等方法,对处方用药进行数据分析,包括对用药频次统计、组方规律进行挖掘等。结果:肝肾亏虚的症状出现54条,症状频次总共224次,其中频率在5以上的18条,总共出现147次,占总数的65.6%。筛选出关于布鲁氏菌病肝肾亏虚证的组方17首,中药38味,使用频次最高的5味中药为牛膝、枸杞子、当归、续断、桑寄生,并取得核心药物组合14条,药物规则主要为牛膝、党参、续断、当归、桑寄生、枸杞子、黄精之间的组合,核心组合4条、得出2个新的处方。结论:中医治疗布鲁氏菌病肝肾亏虚证用药以补肝肾、强筋骨、祛风湿、养气血之品为主,新方组成体现了祛邪扶正、标本兼顾,可使肝肾强、风湿除而血气足、痹痛愈。

增强MRI采用LI-RADS v2018对肝细胞癌的诊断效能

目的:探讨增强MRI采用2018版肝脏影像报告和数据系统(LI-RADS)在高危人群中对肝细胞癌(HCC)的诊断效能。方法:回顾性分析本院2017年至2022年经病理证实的69例HCC患者,并且行MRI增强检查。基于LI-RADS v2018,对每个病灶MRI图像的主要/辅助征象进行评价及LI-RADS分类。以病理结果为金标准,评价增强MRI采用LI-RADS v2018对HCC的诊断效能。采用组内相关系数(ICC)评价阅片者的一致性。结果:3位阅片者间LI-RADS分类的ICC值为0.782(95%可信区间0.713~0.841)。基于LI-RADS v2018,以LR-5为诊断标准,MRI阅片者1诊断HCC的敏感度、特异度和准确率分别为83.9%、70.4%和79.8%;阅片者2分别为80.6%、74.1%和78.7%;阅片者3分别为80.6%、77.8%和79.8%。以LR-4联合LR-5为诊断标准,阅片者1诊断HCC的敏感度、特异度和准确率分别为93.5%、63.0%和84.3%,阅片者2分别为90.3%、66.7%和83.1%,阅片者3分别为91.9%、66.7%和84.3%。结论:基于LI-RADS v2018,增强MRI在高危人群中诊断HCC具有较高的诊断价值。

MRI特征评分模型预测增殖型肝细胞癌

目的观察MRI特征评分模型预测增殖型肝细胞癌(HCC)的价值。方法回顾性分析241例经病理证实HCC患者,包括90例增殖型HCC、151例非增殖型HCC;采用单因素及多因素logistic回归分析比较组间临床及基于2018版肝脏影像报告和数据系统评估的MRI表现,筛选增殖型HCC的独立预测因素,根据其权重赋分并构建评分模型。绘制受试者工作特征(ROC)曲线,计算曲线下面积(AUC),评估模型预测效能;根据评分最佳截断值将患者分为高、低增殖风险亚组,比较组间及亚组间无复发生存(RFS)率和早期RFS率。结果MRI显示肿瘤晕状强化、动脉期环形高强化、瘤内血管、大量病灶实质低强化及边缘不规则均为增殖型HCC的独立预测因素(OR=3.287、2.362、4.542、2.997、2.379,P均<0.05),分别赋分7、5、9、7、5分,总分0~33分;以之建立的评分模型预测增殖型HCC的AUC为0.818。以9分为最佳截断值进行判断,高、低增殖风险分别为97例及144例。组间、亚组间RFS率及早期RFS率差异均有统计学意义(P均<0.05)。结论MRI特征评分模型可有效预测增殖型HCC。

基于复杂网络分析吴力群治疗抽动障碍用药规律

目的探究吴力群教授治疗小儿抽动障碍的用药规律。方法收集吴力群教授2016年9月-2022年10月诊治抽动障碍患儿病案,建立数据库,使用SPSS Statistics 23进行频数统计,使用Liquorice软件进行多尺度骨干网络分析及多层核心网络分析,总结用药规律。结果共纳入病案709则,涉及处方834首,中药203味。药物类别多为补虚药、清热药、平肝熄风药,药性以温、寒、平性为主,归经多归肺经、肝经、脾经。复杂网络分析显示核心处方由当归、白芍、川芎、党参、等20味中药组成,得到30组常用药对,以及不同症状及共患病常用药物。结论吴力群教授治疗小儿抽动障碍重在从“肝风”论治,疏散外风截断病程,平肝潜阳以熄内风,并重视调达肝气,滋阴柔肝,养血熄风。

CT LI-RADS v2018专项培训提高医师对肝脏局灶病变诊断效能的研究

目的:探讨肝脏影像报告和数据系统(LI-RADS)v2018专项培训对提升医师对肝细胞癌(HCC)高危人群肝脏局灶性病变的征象评估及分类的准确性的价值。方法:回顾性收集首都医科大学附属友谊医院行肝脏增强CT扫描的HCC高危患者,最终共纳入63例患者的70个病灶,其中有27个HCC病变,15个非HCC恶性病变和28个良性病变。18位不同年资的影像诊断医师参加CT LI-RADS v2018专项培训。受试医师在参加培训前后分别独立判读入组病灶图像并记录结果,包括对入组病灶的LI-RADS主要征象及支持HCC的辅助征象识别和LI-RADS分类。将病变分类为LR-5即可诊断HCC,计算受试医师在LI-RADS培训前后评估LI-RADS主要征象及支持HCC的辅助征象和诊断HCC的敏感度、特异度、阳性预测值、阴性预测值、阳性似然比、阴性似然比及准确率并计算受试者操作特征(ROC)曲线下面积(AUC)。采用非参数检验比较培训前后对LI-RADS主要征象和支持HCC的辅助征象评估效能及HCC的诊断效能。结果:培训后受试医师对LI-RADS的主要征象及支持HCC的辅助征象的识别效能均较培训前有提升(P值均<0.05),其中对非边缘性廓清、强化包膜以及辅助征象中的无强化包膜识别效能提升较为显著。培训前后受试医师对HCC诊断的敏感度、特异度、阳性预测值、阴性预测值和准确率分别为45.9%、80.9%、60.1%、70.4%、67.4%和55.8%、91.0%、79.5%、76.6%、77.4%(P值均<0.05)。结论:CT LI-RADS专项培训能提升医师对HCC高危人群肝局灶病变的征象评估及诊断能力,其专项培训具有确切的推广意义和价值。

基于数据挖掘的急性肝损伤动物模型应用分析

目的探究各类急性肝损伤动物模型的造模要素,为急性肝损伤动物模型的建立和评价提供参考和建议。方法在中国知网(CNKI)、万方(WanFang)、重庆维普(VIP)、中华医学期刊全文数据(Yiigle)、PubMed等数据库检索2002~2022年急性肝损伤动物实验文献,归纳总结文献中涉及到的急性肝损伤动物模型的动物种类、阳性对照药、造模方法、造模药及给药剂量、给药时间和检测指标,应用Excel、SPSS Modeler18.0、Cytoscape3.8.2对结果进行分析。结果数据库共纳入896篇文献,急性肝损伤动物模型中应用最多的是雄性KM小鼠;造模方法以化学性肝损伤、酒精性肝损伤、药物性肝损伤和免疫性肝损伤四大类为主,分别对应的主要造模方式为:①实验前24 h腹腔注射10.0 mL/kg 0.1%CCl_(4)植物油;②实验前16 h灌胃12.0 mL/kg 50.0%~56.0%乙醇;③实验前24 h腹腔注射APAP 300 mg/kg;④实验前8 h尾静脉注射Con A 20 mg/kg。模型的评价以肝病理指标为金标准,结合生化指标血清ALT、AST,肝组织匀浆SOD、MDA含量及活性为直接指标。结论临床上急性肝损伤发病原因各异,在制备急性肝损伤动物模型时应根据特定的研究内容、研究特点选择对应的造模方法。

基于临床资料、超声造影LI-RADS联合异常凝血酶原的肝癌微血管侵犯列线图模型的构建及验证

目的基于临床资料、超声造影肝脏影像报告和数据系统(LI-RADS)联合异常凝血酶原前体蛋白(PIVKA-Ⅱ)的肝癌微血管侵犯(MVI)列线图模型的构建,并对所构建的列线图模型进行验证。方法选取2019年1月至2023年12月该院收治的312例肝癌患者作为研究对象,按照2∶1分为建模集组(208例)和验证集组(104例)。以单因素和多因素Logistic回归分析肝癌MVI的影响因素,采用R3.6.1软件绘制肝癌MVI预测列线图模型;以预测风险能力指数(C-index)、校准曲线、受试者工作特征(ROC)曲线评价列线图模型的预测能力,以决策曲线评价列线图模型的临床效用。结果建模集组与验证集组MVI发生率分别为32.21%(67/208)、27.88%(29/104),建模集组与验证集组年龄、性别、体质量指数等基线资料及MVI发生情况比较,差异均无统计学意义(P>0.05)。单因素分析结果显示,建模集组中MVI组中国肝癌分期为Ⅱ~Ⅲ期患者占比及甲胎蛋白水平均高于无MVI组,差异均有统计学意义(P<0.05);建模集组中MVI组肿瘤最大径大于无MVI组,LI-RADS分级为5级患者占比及PIVKA-Ⅱ水平均高于无MVI组,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,甲胎蛋白水平升高、肿瘤最大径增大、LI-RADS分级为5级患者占比较高、PIVKA-Ⅱ水平升高均为肝癌MVI的独立危险因素(P<0.05)。预测肝癌MVI的列线图模型的C-index为0.936(95%CI:0.894~0.965),区分度良好。Bootstrap内部验证和外部验证结果显示,列线图模型在建模集和验证集中的一致性指数分别为0.859、0.840。ROC曲线分析结果显示,列线图模型预测肝癌MVI的AUC为0.936,高于单独的甲胎蛋白(0.839)、肿瘤最大径(0.792)、LI-RADS分级(0.705)、PIVKA-Ⅱ(0.813)。决策曲线分析结果显示,当建模集高风险阈值为0.00~0.93、验证集高风险阈值为0.00~0.78时该列线图模型具有较好的临床净收益。结论甲胎蛋白、肿瘤最大径、LI-RADS分级和PIVKA-Ⅱ与肝癌MVI均有关,均可作为肝癌MVI的联合预测因子,可提高术前诊断肝癌MVI的效能,为临床肝癌的诊断和治疗提供客观准确的决策支持。

基于LI-RADS v2018及MRI特征对肝细胞癌CK19表达的风险预测及预后评估

目的 探讨2018版肝脏影像报告和数据系统(Liver Imaging Reporting and Data System version 2018,LI-RADS v2018)对肝细胞癌(hepatocellular carcinoma,HCC)细胞角蛋白19(cytokeratin 19,CK19)表达的术前预测及预后评估的价值。材料与方法 回顾性分析220例术前接受MRI检查并经病理证实为HCC患者的临床、病理及影像资料,包括CK19阳性组59例,CK19阴性组161例。将患者按7∶3比例分为训练集和验证集。通过单因素与多因素logistic回归分析确定CK19阳性表达HCC的独立预测因素并构建列线图评分模型。采用受试者工作特征(receiver operating characteristic,ROC)曲线分析模型诊断效能,绘制校准曲线、决策曲线评价模型的校准性能和临床适用性。计算患者的列线图得分并进行高低风险分组,采用Kaplan-Meier生存曲线分析比较不同亚组患者的总体、早期及晚期无复发生存率。结果 晕状强化(OR=3.432,P=0.045)、环形动脉期高强化(OR=32.073,P=0.017)、靶样扩散受限(OR=12.941,P=0.006)、不光滑肿瘤边缘(OR=4.590,P=0.014)及肝胆期肿瘤-肝实质相对增强比(the relative enhancement ratio,RER)(OR=0.014,P=0.023)是CK19阳性表达HCC的独立预测因素。预测模型在训练集和验证集的曲线下面积(area under the curve,AUC)分别为0.884(95%CI:0.823~0.930)、0.748(95%CI:0.625~0.846),校准曲线、决策曲线显示模型的校准性能和临床适用性较好。CK19阳性与阴性组的总体无复发生存率、高与低风险组的总体、早期及晚期无复发生存率之间均存在显著差异(P<0.05)。结论 晕状强化、环形动脉期高强化、靶样扩散受限结合不光滑肿瘤边缘、肝胆期增强定量参数可对HCC的CK19表达进行术前风险预测,并有助于评估HCC术后复发。

基于堆叠降噪自编码器的肝癌亚型分类

肝癌是威胁人类健康的常见恶性肿瘤之一。通过对基因数据使用深度学习方法进行整合来系统地获取对肝癌的认知,使用多组学的疾病分析方法来探究各组学之间的相互关系,有助于更准确的临床决策。然而,由于多组学数据具有高维稀疏性,存在大量的冗余特征和较少的可用临床标签样本。堆叠降噪编码器(SDAE)是能够从海量数据中获取有效特征的高效模型,因此基于SDAE模型提出一种层次式堆叠降噪编码器,来学习肝癌的RNA表达、miRNA表达和DNA甲基化数据的特征并进行整合和识别。实验结果表明:Hi-SDAE方法提高了对肝癌亚型分类的准确度,为肝癌针对性治疗提供了更有价值的参考依据。

基于数据挖掘及网络药理学探讨肝郁脾虚型肝癌用药规律及作用机制

目的:挖掘目前中医治疗肝郁脾虚型肝癌的组方用药规律,分析处方相关的药物靶点及疾病通路,探索核心处方的潜在作用机制。方法:检索纳入CNKI、维普、万方中关于肝癌的中医临床文献,运用Microsoft Excel 2021进行中药频数和性味归经统计,通过SPSS Modeler 18.0软件Apriori算法进行关联规则分析,运用SPSS 25.0软件分析组方用药规律;运用TCMSP平台检索核心药物的有效成分及靶点,在人类基因GeneCards数据库得到肝癌靶基因,将核心药对及肝癌靶基因同时导入Venny 2.1.0平台得到药物-疾病交集靶点。采用Cytoscape3.9.0构建药物-疾病-靶基因网络图,利用metascape平台进行基因本体(GO)功能和KEGG通路富集分析。结果:共筛选出45篇文献,83首处方,高频药物前5位分别为:柴胡、白术、茯苓、甘草、白芍。药性以温、寒为主,药味以辛、甘、苦味为主,归经以肝、脾、肺和胃经为主。共获得20组关联药物,核心药物聚类处方4首。获得核心药物有效成分112种、药物靶点209个、疾病靶点16458个,疾病-药物交集靶点204个。GO功能富集分析获得生物过程1840个、细胞组分113个、分子功能215个,KEGG通路富集分析获得209条信号通路。结论:治疗肝郁脾虚型肝癌的中药主要通过调控Akt1、白细胞介素-6、白细胞介素-1B重组蛋白等关键靶点发挥作用。

基于数据挖掘探析钱英治疗原发性肝癌用药规律

目的通过数据挖掘技术分析钱英教授治疗原发性肝癌的用药规律,为临床辨治原发性肝癌提供思路。方法收集2008年11月-2020年8月钱英教授治疗原发性肝癌的门诊中药处方,整理后建立数据资料表,通过Excel2019对药物频次及性味归经进行分析;通过名医传承辅助平台医案分析模块对筛选出的中药处方进行核心药物分析,药对之间的共生性分析,药症关联分析及药物聚类分析。结果共纳入处方108首,涉及中药188味,药物总频次为1322。高频用药包括白花蛇舌草、黄芪、槲寄生、郁金、丹参等。药性以寒、平、温为主,药味以苦、甘、辛为主,归经以肝经、脾经、肾经、胃经为主。药物关联中高频药物组合有郁金-水红花子、槲寄生-莪术等9对。药症关联分析中关联度较高的有“胃痛-丹参”“癥瘕-赤芍、陈皮”“耳鸣-南沙参、枸杞子、槲寄生”“舌下络脉延长-莪术、水红花子、丹参”等。药物聚类分为3类潜在的药物群。结论钱英教授治疗原发性肝癌多用清热药、补虚药、行气活血药,以槲芪散为主方随证加减,以清热解毒、疏肝解郁、逐瘀通络治其标,补气健脾、和血调肝、滋补肝肾治其本,可为临床治疗原发性肝癌提供一定参考。

从痰湿论治非酒精性脂肪性肝病的用药规律及作用机制分析

目的:挖掘从痰湿论治非酒精性脂肪性肝病(NAFLD)的处方用药规律,分析核心处方药物发挥作用的潜在机制。方法:搜集从痰湿论治NAFLD的临床研究文献,对处方药物的性味、归经进行系统聚类与关联规则分析。得出从痰湿论治NAFLD的核心处方后,检索数据库获取药物有效成分作用靶点及疾病靶点,二者取交集后在STRING数据库构建蛋白质-蛋白质相互作用关系网络,并在Cytoscape中对所有交集靶点进行评分以获取核心靶点。对关键靶点进行基因本体功能富集分析、京都基因和基因组百科全书通路富集分析,并将分析结果导入Cytoscape软件构建中药活性成分-靶点-疾病通路网络图。结果:筛选后共得到119首方药,涉及153味药物,多为甘味、温性,以归肝、脾经多见。关联规则分析结果显示,山楂、茯苓、泽泻、白术、丹参、半夏和陈皮是治疗NAFLD的核心药物。聚类分析得到核心处方组合“山楂、决明子、泽泻、丹参、柴胡、郁金”,网络药理学分析结果显示,核心处方与NAFLD交集靶点有248个,信号转导及转录激活因子3和细胞外基质致癌基因是从痰湿论治NAFLD最核心的靶点。叉头框O、肿瘤坏死因子和磷脂酰肌醇3激酶-蛋白激酶B信号通路等是从痰湿论治NAFLD的主要信号通路。甲基庚烯酮、槲皮素及山柰酚等是核心处方发挥作用的主要有效成分。结论:从痰湿论治NAFLD以甘味、温性药物为主,离不开对肝、脾的调理,山楂、茯苓、泽泻、白术、丹参、半夏和陈皮是从痰湿论治NAFLD的常用药物;从痰湿论治NAFLD的核心处方主要通过参与调节脂质代谢、炎症反应和氧化应激等生物学过程,发挥对NAFLD的治疗作用。