ABSTRACT Aims/Introduction The optimal therapy for latent autoimmune diabetes in adults (LADA) remains undefined. Increasing evidence has shown that sitagliptin and insulin treatment can benefit patients with LADA, but the efficacy still lacks systematic evaluation. We carried out this systematic review and meta‐analysis to summarize the current data on the efficacy and safety of sitagliptin combined with insulin on LADA, providing a reliable reference for the effective therapeutic treatment of LADA patients. Materials and Methods We retrieved the literature in PubMed, Cochrane Library, Embase, Web of Science and CNKI from inception to August 2021. Randomized controlled trials comparing the effects of sitagliptin plus insulin with insulin alone in LADA patients were identified. The outcome measures included parameters of glycemic control, β‐cell function, body mass index and adverse events. The Review Manager 5.2 and Stata 14.0 were utilized for data analysis. Results Eight randomized controlled trials involving 295 participants were identified. Sitagliptin and insulin treatment lowered hemoglobin A1c (weighted mean difference −0.36, 95% confidence interval −0.61 to −0.10, I2 = 91.6%), increased fasting C‐peptide (weighted mean difference 0.08, 95% confidence interval −0.02 to 0.17, I2 = 88.8%) and had fewer adverse events compared with insulin alone. The inter‐study heterogeneity, potential publication bias and other factors might interpret asymmetrical presentation of funnel plots. There was no significant association between sitagliptin plus insulin treatment and levels of hemoglobin A1c or fasting C‐peptide, regardless of the duration of intervention and sample size. Conclusions Sitagliptin combined with insulin can achieve better glycemic control and improve islet β‐cell function with lower incidence of hypoglycemia compared with insulin alone, which provides an effective and tolerated therapeutic regimen for LADA patients. However, further well‐designed and rigorous randomized controlled trials are required to validate this benefit due to the limited methodology quality of included trials.

目的:比较我国岭南和华北地区名老中医辨治非酒精性脂肪性肝病(NAFLD)的用药规律异同.方法:从数据库和书籍搜集岭南、华北地区名老中医治疗NAFLD的处方,从用药频次、类别、性味归经与配伍规律的角度分析两地医家治疗NAFLD用药习惯的异同.结果:两地有16味共同的高频药物;主要药物类别均为补益药、利水渗湿药与活血化瘀药等;共同的核心药物配伍为泽泻、山楂、郁金、丹参和柴胡.差异在于岭南地区使用归脾经药物更多(P<0.05),多用白芍、决明子、茯苓、甘草、荷叶、莱菔子与三七(P<0.05);华北地区则多用赤芍、黄芪、当归与延胡索.结论:两地名老中医均以健脾祛湿、活血理气消滞为NAFLD的基本治则,各自特色在于,岭南更侧重健脾祛湿、益气养阴、理气化痰,且用药较平和;华北更侧重疏肝活血和养肝清热.

目的:系统评价化滞柔肝颗粒治疗非酒精性脂肪性肝病(Non-alcoholic Fatty Liver Disease,NAFLD)的疗效和安全性.方法:计算机检索中国知识资源总库(CNKI)、中文科技期刊数据库(维普网)、中国学术期刊数据库(万方数据)、中国生物医学文献数据库(CBM)、Cochrane Library、PubMed、Web of Science、Embase和Scopus,并手工检索.检索范围为建库至2020年11月.收集基础治疗结合化滞柔肝颗粒治疗NAFLD(试验组),对比基础治疗结合其他药物治疗的临床随机对照试验(Randomized Controlled Trials,RCTs),提取资料并运用Cochrane协作网偏倚风险评估工具进行质量评价,采用RevMan5.4进行Meta分析.结果:共纳入13个RCTs,涉及患者1651例.Meta分析结果显示,与对照组相比,试验组总有效率[比值比(Odds Ratiio,OR)=3.40,95％置信区间(Confidence Interval,CI)[2.51,4.61],P<0.00001)]、谷丙转氨酶(Alanine Transaminase,ALT)[均属差(Mean Difference,MD)=-16.15,95％CI[-26.01,-6.29],P=0.001)]、谷草转氨酶(Aspartate Transaminase,AST)(MD=-14.03,95％CI[-21.05,-7.02],P<0.001)、总胆固醇(Total Cholestorel,TC)(MD=-0.74,95％CI[-1.00～-0.47],P<0.00001)、甘油三酯(Triglyceride,TG)(MD=-0.32,95％CI[-0.51,-0.13],P=0.0008)、BMI(MD=-1.81,95％CI[-2.82～-0.80],P=0.0004)差异具有统计学意义;而γ-谷氨酰转移酶(γ-glutamyl Transpeptidase,γ-GGT)(MD=-3.61,95％CI[-7.44,0.21],P=0.06)、不良反应(RR=0.84,95％CI[0.48,1.47],P=0.54)差异不具有统计学意义.结论:化滞柔肝颗粒治疗非酒精性脂肪性肝病的疗效优于对照组,且具有一定的安全性,但需更多高质量RCT进行验证.

目的:探究现代岭南医家治疗原发性肝癌(PHC)的中药组方规律及用药经验.方法:以中国期刊全文数据库(CNKI)、万方数据库中的现代文献为数据来源,使用中医传承辅助平台(V2.5)进行分析,探究现代岭南医家运用中药治疗肝癌的组方规律.结果:从CNKI、万方数据库中搜索、整理出292首治疗肝癌的方剂,共使用278种中药,20对中药常用组合,挖掘出20个核心组合,演化出10个新处方.通过分析,发现现代岭南医家治疗肝癌多以疏肝健脾、利水渗湿、祛瘀解毒为治疗大法,采用道地药材,因地制宜,具有岭南中医特色.结论:用数据挖掘方法客观地呈现出现代岭南医家运用中医药治疗肝癌的用药规律,为岭南地区肝癌的新药研发提供思路.

单纯性肥胖是高血压、糖尿病、心脑血管疾病等滋生的土壤,影响人类的身体健康.中医药治疗单纯性肥胖具有良好的临床疗效,现从病因病机、辨证治疗及中医外治法等方面,将近年来中医药治疗单纯性肥胖的研究进展作一述评.单纯性肥胖多辨证为脾虚湿阻、胃肠实热、脾肾阳虚、痰瘀互结等,主要治法有健脾祛湿、温补脾肾、清热解毒、化痰祛瘀等.单味中药、中药复方辨证论治、中医外治法均在治疗单纯性肥胖方面发挥着重要作用.目前临床研究的规范化有待提高,作用机制探讨有待深入,为单纯性肥胖的进一步临床与科研工作提供参考.

BACKGROUND:Acupuncture has been widely used to treat diabetic peripheral neuropathy (DPN) in China as a complementary and alternative therapy. This study aims to summarize the characteristics and evaluate the methodology quality of the systematic reviews (SRs) regarding acupuncture for DPN.METHODS:A comprehensive literature search was performed from inception to February 2020. We assessed the methodological quality of the included SRs with the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool, adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist to evaluate the reporting characteristics of included SRs, and utilized the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to evaluate the quality of evidence for outcomes including total effective rate, sensory nerve conduction velocity, motor nerve conduction velocity and adverse events. One-way analysis of variance and multiple linear regression were conducted to evaluate the associations between characteristics and two index scores (PRISMA and AMSTAR 2).RESULTS:Eighteen SRs were included in this overview. The methodology quality of the included SRs ranged from very low to high. Only protocol registration and funding source reported were associated with the AMSTAR 2 index scores, while no variable showed significant difference in the PRISMA scores. The overall quality of evidence in included SRs ranged from "very low" to "moderate".CONCLUSION:This overview suggested beneficial effects of acupuncture on DPN, whereas the results should be interpreted with cautious owing to methodology flaws, providing reference for further improvement of the study design.

Background: The prognosis of patients with advanced hepatocellular carcinoma (HCC) is still poor, effective therapeutic targets are needed. ZW10 interacting kinetochore protein (Zwint) is an essential component of the mitotic spindle checkpoint and is upregulated in cancers. Disappointing, the role of ZWINT in HCC has not been fully illuminated. Methods: Multiple tools, including TIMER2.0, Oncomine, GEPIA2, UALCAN, LinkedOmics, Kaplan-Meier Plotter, cBioPortal, and MethSurv, etc. were applied to comprehensively analyze the expression, genetic alternations, clinicopathological relevance, prognostic value, and DNA methylation of ZWINT, along with its correlations with immune infiltration in HCC. Besides, gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) analysis were performed for the correlated genes of ZWINT, closely interconnected clusters and hub proteins in the PPI network were discovered to learn the underlying biological mechanisms. Results: We found ZWINT was significantly upregulated in diverse cancers including HCC, compared with the corresponding normal controls. ZWINT upregulation was significantly associated with unfavorable clinicopathological features and survivals of HCC patients. Genetic alternations of ZWINT frequently occurred, which were linked to worse outcomes of HCC patients. The results of GSEA displayed ZWINT and its correlated genes might be components of condensed chromosomes and spindles, which participated in biological processes and signaling pathways involving DNA replication, cytokinesis, and cell cycle checkpoint, etc. Three highly interconnected clusters and 10 hub proteins were identified from the PPI network constructed with the correlated genes of ZWINT. Moreover, ZWINT expression was found positively correlated with infiltration levels of various immune cells, especially myeloid-derived suppressor cells. Conclusion: This study demonstrated ZWINT might be a promising unfavorable prognostic biomarker and a therapeutic target of HCC, which could regulate HCC progression through cell division and immunosuppression.

Background: High mobility group box (HMGB) proteins are DNA chaperones involved in transcription, DNA repair, and genome stability. Extracellular HMGBs also act as cytokines to promote inflammatory and immune responses. Accumulating evidence has suggested that HMGBs are implicated in cancer pathogenesis; however, their prognostic and immunological values in pan-cancer are not completely clear. Methods: Multiple tools were applied to analyze the expression, genetic alternations, and prognostic and clinicopathological relevance of HMGB in pan-cancer. Correlations between HMGB expression and tumor immune-infiltrating cells (TIICs), immune checkpoint (ICP) expression, microsatellite instability (MSI), and tumor mutational burden (TMB) in pan-cancer were investigated to uncover their interactions with the tumor immune microenvironment (TIME). Gene set enrichment analysis (GSEA) was conducted for correlated genes of HMGBs to expound potential mechanisms. Results: HMGB expression was significantly elevated in various cancers. Both prognostic and clinicopathological significance was observed for HMGB1 in ACC; HMGB2 in ACC, LGG, LIHC, and SKCM; and HMGB3 in ESCA. Prognostic values were also found for HMGB2 in KIRP and MESO and HMGB3 in BRCA, SARC, SKCM, OV, and LAML. The global alternation of HMGBs showed prognostic significance in ACC, KIRC, and UCEC. Furthermore, HMGBs were significantly correlated with TIIC infiltration, ICP expression, MSI, and TMB in various cancers, indicating their regulations on the TIME. Lastly, results of GSEA-illuminated genes positively correlated with HMGBs which were similarly chromosome components participating in DNA activity-associated events. Conclusion: This study demonstrated that HMGBs might be promising predictive biomarkers for the prognosis and immunotherapeutic response, also immunotherapy targets of multiple cancers.

Nonalcoholic fatty liver disease (NAFLD) is a rising global public health concern due to its prevalence. Danning Tablets (DNt), a composite prescription of Chinese herbal medicine, shows significant curative effects on NAFLD in clinical application. This study aimed to decipher the bioactive substances and potential mechanisms of action of DNt in the treatment of NAFLD, applying an integrated network pharmacology approach. First, the bioactive compounds of DNt were screened based on their pharmacokinetic properties, and the corresponding drug targets were predicted. Then, the NAFLD-related targets were collected. The overlapping targets between the putative targets of DNt and NAFLD-related targets were identified as the potential therapeutic targets of DNt against NAFLD. Subsequently, the networks were constructed and analyzed, and the key bioactive compounds and targets were screened out depending on their importance in the networks. Functional enrichment analysis was carried out to elucidate the potential mechanisms of DNt acting on NAFLD. Finally, a molecular docking simulation was implemented to assess the potential binding affinity between the key targets and the bioactive compounds. As a result, 43 bioactive compounds of DNt and 69 putative targets were identified. Based on the network analysis, we found seven key bioactive compounds (quercetin, ß-sitosterol, luteolin, kaempferol, supraene, curcumenolactone C, and stigmasterol) of DNt might treat NAFLD via intervening IL6, MAPK8, VEGFA, CASP3, ALB, APP, MYC, PPARG, and RELA. The functional enrichment analysis revealed that DNt might affect NAFLD by modulating the signaling pathways involved in lipid metabolism, inflammation, oxidation, insulin resistance (IR), atherosclerosis, and apoptosis. Furthermore, most key bioactive compounds might bind firmly with the key targets. This study predicted the multicomponent, multitarget, and multipathway mechanisms of DNt in the treatment of NAFLD from a holistic perspective. DNt could be a promising agent for NAFLD, but further experimental verifications are still needed.

The prognosis of patients with gastric cancer (GC) is still unsatisfying. Numerous markers of gastric cancer stem cells (GCSCs) have been identified and were thought to be related to cancer aggressiveness. However, the roles of GCSC markers in GC patients’ prognosis and immune infiltration remain unknown. Expression of GCSC markers was analyzed using Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA). Their associations with clinicopathological parameters were analyzed using UALCAN and LinkedOmics. Alternations and protein expression of GCSC markers were analyzed by cBioPortal and the Human Protein Atlas databases, respectively. The prognostic significance of GCSC markers was evaluated using Kaplan-Meier plotter. Correlations between the expression of GCSC markers and immune infiltration along with biomarkers of tumor-infiltrating immune cells (TIICs) were assessed combined Tumor Immune Estimation Resource and GEPIA. GeneMANIA was used to discover the interactive genes of GCSC markers, and enrichment analysis was performed using Database for Annotation, Visualization, and Integrated Discovery server. We identified six GCSC markers significantly up-expressed in GC, compared with normal stomach tissues. Among them, the overexpression of ICAM1, THY1, and CXCR4 significantly indicated adverse, while EPCAM indicated beneficial clinicopathological features of GC patients. The up-regulation of CXCR4 showed unfavorable prognostic significance, whereas EPCAM and TFRC showed the opposite. The six GCSC markers were all correlated with the infiltration and activation of distinct TIICs. Especially, ICAM1, THY1, and CXCR4 showed strongly positive correlations with tumor-associated macrophages. Besides, chemokine, Toll-like receptor, NF-kappa B, and HIF-1 signaling pathways might be involved in the regulation of GCSC markers on cancer development. This study proposed that GCSC markers might be promising targets of GC treatment to weaken cancer stem-like properties and strengthen anticancer immunity.

The occurrence of portal vein tumor thrombus (PVTT) is strongly correlated to the staging and poor prognosis of hepatocellular carcinoma (HCC) patients. However, the mechanisms of PVTT formation remain unclear. This study aimed to investigate differentially expressed genes (DEGs) between primary tumor (PT) and PVTT tissues and comprehensively explored the underlying mechanisms of PVTT formation. The DEGs between PT and paired PVTT tissues were analyzed using transcriptional data from the Gene Expression Omnibus (GEO) database. The expression, clinical relevance, prognostic significance, genetic alternations, DNA methylation, correlations with immune infiltration, co-expression correlations, and functional enrichment analysis of the DEGs were explored using multiple databases. As result, 12 DEGs were commonly down-expressed in PVTT compared with PT tissues among three datasets. The expression of DCN, CCL21, IGJ, CXCL14, FCN3, LAMA2, and NPY1R was progressively decreased from normal liver, PT, to PVTT tissues, whose up-expression associated with favorable survivals of HCC patients. The genetic alternations and DNA methylation of the DEGs frequently occurred, and several methylated CpG sites of the DEGs significantly correlated with outcomes of HCC patients. The immune infiltration in the tumor microenvironment of HCC was correlated with the expression level of the DEGs. Besides, the DEGs and their co-expressive genes participated in the biological processes of extracellular matrix (ECM) organization and focal adhesion. In summary, this study indicated the dysregulation of ECM and focal adhesion might contribute to the formation of PVTT. And the above seven genes might serve as potential biomarkers of PVTT occurrence and prognosis of HCC patients.

BACKGROUND:The prognosis of patients with advanced hepatocellular carcinoma (HCC) remains poor. Lipid remodeling modulators are considered promising therapeutic targets of cancers, owing to their functions of facilitating cancer cells' adaption to the limited environment. Lysophosphatidylcholine acyltransferases (LPCATs) are enzymes regulating bio-membrane remodeling, whose roles in HCC have not been fully illuminated.METHODS:Multiple bioinformatic tools were applied to comprehensively evaluate the expression, genetic alterations, clinical relevance, prognostic values, DNA methylation, biological functions, and correlations with immune infiltration of LPCATs in HCC.RESULTS:We found LPCAT1 was significantly overexpressed and the most frequently altered in HCC. The high-expression of LPCAT1/4 indicated clinicopathological advancements and poor prognoses of HCC patients. Even though the global DNA methylation of LPCATs in HCC showed no significant difference with that in normal liver, the hypermethylation of numerous CpG sites of them implied worse survivals of HCC patients. Thirty LPCATs' interactive genes were identified, which were generally membrane components and partook in phospholipid metabolism pathways. Finally, we found the expression of LPCATs was extensively positively correlated with the infiltration of various stimulatory and suppressive tumor-infiltrating immune cells (TIICs) in the tumor microenvironment.CONCLUSION:This study addressed LPCAT1/4 were potential prognostic and immunotherapeutic biomarkers of HCC targeting bio-membrane lipid remodeling.

Background: C-x-C motif chemokine ligands (CXCLs) are critical regulators of cancer immunity and angiogenesis, which affect disease progression and treatment responses. The character of each CXCL in the prognosis and immune infiltration of hepatocellular carcinoma (HCC) patients is unclear yet. Methods: Differentially expressed CXCLs between HCC and normal control were screened by Oncomine and GEPIA2. Genetic alternations of CXCLs in HCC were analyzed by cBioPortal. Clinicopathological relevance of CXCLs in HCC patients was analyzed using UALCAN. The prognostic value of CXCLs was evaluated using univariate and multivariate analyses. Correlations of CXCLs' expression with immune infiltration, chemokines and their receptors were assessed integrating TIMER, TISIDB, and GEPIA2. The co-expressed genes of CXCLs were discovered, and functional enrichment analysis was performed for them. Results: CXCL9/10 was significantly higher expressed while CXCL2/12/14 was lower expressed in HCC than normal tissues, but they didn't show significant clinicopathological relevance in HCC patients. High-expression of CXCL2/10/12/14 indicated favorable outcomes of HCC patients. The expression of CXCL9/10/12/14 was significantly positively correlated with not only the infiltration and biomarkers' expression of various tumor-infiltrating immune cells but also the abundance of chemokines and their receptors. The co-expressed genes of the five CXCLs were extracellular components and regulated immune or inflammatory responses and signaling pathways of chemokine, Toll-like receptor and tumor necrosis factor might be involved. Conclusion: The present study proposed CXCL2/10/12/14 might predict outcomes of HCC patients and were extensively related with the immune microenvironment in HCC. It would be a prospective therapeutic strategy for HCC to enhance effective immunity surveillance through intervening in these CXCLs.

Background. Aidi injection (ADI) is an effective Traditional Chinese medicine preparation widely used for lung cancer. However, the pharmacological mechanisms of ADI on lung cancer remain to be elucidated. Methods. A network pharmacology (NP)-based approach and the molecular docking validation were conducted to explore underlying mechanisms of ADI on lung cancer. The compounds and target genes were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (Batman-TCM) database. The STRING database was utilized for protein interaction network construction. The R package clusterProfiler was used for bioinformatics annotation of hub target genes. The gene expression analysis and survival analysis were performed based on The Cancer Genome Atlas (TCGA) database. The Autodock Vina was used for molecular docking validation. Results. A total of five key compounds with 324 putative target genes were screened out, and 14 hub target genes were identified for treating lung cancer. Six hub genes could influence the survival of non-small cell lung cancer (NSCLC) patients. Of these hub genes, the expression pattern of EGFR, MYC, PIK3CA, and SMAD3 were significantly higher in the LUSC, while PIK3CA and RELA expressed lower in the LUAD group and LUSC group, respectively. These six hub genes had good docking affinity with the key compounds of ADI. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that ADI may exert therapeutic effects on lung cancer by regulating critical pathways including the thyroid hormone signaling pathway, MAPK signaling pathway, and PI3K-Akt signaling pathway. Conclusions. The present study explored the potential pharmacological mechanisms of ADI on lung cancer, promoting the clinical application of ADI in treating lung cancer, and providing references for advanced researches.

目的 分析首诊乙型肝炎病毒相关肝细胞癌(HBV-HCC)患者发生门静脉癌栓(PVTT)和肝外转移(EHM)的独立危险因素,构建并评价风险预测列线图.方法 选取200例首诊HBV-HCC患者,采用单因素和多因素Logistic回归分析其发生PVTT和EHM的独立危险因素.用R软件构建风险评分列线图,绘制受试者工作特征(ROC)曲线、校准曲线及决策曲线评估列线图的预测效果及临床效用.结果 200例首诊HBV-HCC的患者中,77例发生PVTT,31例发生EHM,21例同时存在PVTT和EHM.多因素Logistic回归分析结果显示,肿瘤大体病理分型为块状型或弥漫型、多发肿瘤、总胆红素水平≥17.1μmol/L、血小板与淋巴细胞比值(PLR)≥128.8均为首诊HBV-HCC患者发生PVTT的独立危险因素(P﹤0.05);肿瘤大体病理分型为块状型或弥漫型、多发肿瘤、中性粒细胞计数≥6.3×109/L均是首诊HBV-HCC患者发生EHM的独立危险因素(P﹤0.05).PVTT和EHM预测列线图的ROC曲线下面积分别为0.857和0.862,有良好的预测能力和临床效益.结论 本研究构建的列线图用于首诊HBV-HCC患者发生PVTT和EHM的个体化预测价值较好,具有临床应用前景.

Background. The heat shock protein 90 (HSP90s) family is composed of molecular chaperones composed of four isoforms in humans, which has been widely reported as unregulated in various kinds of cancers. Nevertheless, the role of each HSP90s isoform in prognosis and immune infiltration in distinct subtypes of breast cancer (BRAC) remains unclear. Methods. Public online databases including the Oncomine, UALCAN, Kaplan-Meier Plotter, Tumor IMmune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), GeneMANIA, and Database for Annotation, Visualization, and Integrated Discovery (DAVID) were integrated to perform bioinformatic analyses and to explore the possible associations among HSP90s gene expression, prognosis, and immune infiltration in BRAC. Results. The mRNA expression of all HSP90s members was elevated in distinct clinical stages and subtypes of BRAC, compared with the normal breast tissue (P<0.05). Overexpressed HSP90AA1 was associated with poor prognosis, particularly, both short overall survival (OS) and release-free survival (RFS) in Basal-like BRAC patients; overexpressed HSP90AB1 and HSP90B1 were both associated with poor RFS in Luminal A BRAC patients, while overexpressed TRAP1 was associated with favorable RFS in Luminal A BRAC patients. Moreover, HSP90s gene expression in BRAC showed correlations with the infiltration of CD8+ T cells, neutrophils, macrophages, and dendritic cells (DCs), as well as the activation of tumor-associated macrophages (TAMs), DCs, and CD4+ helper T (Th) cells. The underlying mechanisms of HSP90s modulating tumor-infiltrating immune cells (TIICs) might be related with their functions in antigen processing and presentation, major histocompatibility complex (MHC) binding, and assisting client proteins. Conclusion. This study demonstrated that HSP90s family genes were overexpressed and might be serve as prognostic biomarkers in subtypes of BRAC. It might be a novel breakthrough point of BRAC treatment to regulate immune infiltration in BRAC microenvironment for more effective anticancer immunity through pharmacological intervention of HSP90s.

Colorectal cancer (CRC) is now the second most deadly cancer globally. Chinese herbal medicine (CHM) plays an indispensable role in CRC treatment in China. However, the core herbs (the CHs) in the treatment of CRC and their underlying therapeutic mechanisms remain unclear. This study aims to uncovering the CHs and their mechanisms of action of CRC treatment, applying data mining and network pharmacology approach. First, CHM prescriptions treating CRC were collected from clinical studies from the Chinese National Knowledge Infrastructure (CNKI) and MEDLINE databases, and the CHs were identified through data mining. Then, the bioactive compounds and the corresponding putative targets of the CHs were obtained from three traditional Chinese medicine (TCM) databases. CRC related targets were acquired from three disease databases; the overlapping targets between the CHs and CRC were identified as the therapeutic targets. Subsequently, functional enrichment analysis was performed to elucidate the mechanisms of the CHs on CRC. Moreover, networks were constructed to screen the major bioactive compounds and therapeutic targets. Finally, prognostic values of the major target genes were evaluated by survival analysis, and molecular docking simulation was performed to assess the binding affinity of key targets and major bioactive compounds. It came out that 10 the CHs from 113 prescriptions and 190 bioactive compounds with 118 therapeutic targets were identified. The therapeutic targets were mainly enriched in the biological progress of transcription, apoptosis, and response to cytokine. Various cancer-associated signaling pathways, including microRNAs, TNF, apoptosis, PI3K-Akt, and p53, were involved. Furthermore, 15 major bioactive compounds and five key target genes (VEGFA, CASP3, MYC, CYP1Y1, and NFKB1) with prognostic significance were identified. Additionally, most major bioactive compounds might bind firmly to the key target proteins. This study provided an overview of the anti-CRC mechanisms of the CHs, which might refer to the regulation of apoptosis, transcription, and inflammation.

目的:探讨参苓白术散治疗新型冠状病毒肺炎(COVID-19)恢复期肺脾气虚证的潜在作用机制及可行性.方法:使用中药数据库筛选参苓白术散的活性成分并预测靶点;运用Cytoscape构建和分析网络;通过靶点间蛋白质相互作用网络提取重要靶点;对重要靶点行生物功能及通路进行富集分析;用iGEMDOCK进行分子对接实验.结果:纳入127种参苓白术散所含活性成分,预测到193个靶点,核心成分为二氢槲皮素、山柰酚和木犀草素等.26个重要靶点富集在免疫炎症反应(白细胞介素17、B细胞及肿瘤坏死因子等通路)、血管紧张素对循环系统的调节和肾上腺素能等神经-内分泌相关功能.5个核心成分具有与COVID-19靶点结合的潜能.结论:参苓白术散可能通过作用于免疫炎症反应、循环及神经-内分泌相关信号通路,结合调理肠道菌群,从而治疗COVID-19恢复期肺脾气虚证.

目的:运用网络药理学方法预测中药肿节风的药效物质基础与潜在机制.方法:选用TCMSP等数据库搜集肿节风的化学成分,并筛选活性成分;预测活性成分潜在的靶点;应用CTD匹配靶点对应的疾病;采用Cytoscape构建和分析网络;采用STRING进行靶点蛋白质相互作用(PPI)分析;应用GlueGO行基因本体(GO)及京都基因组百科全书(KEGG)通路富集分析;采用iGEMDOCK进行分子对接.结果:筛选出22个肿节风活性成分,可作用于116个靶点治疗18类疾病.淫羊藿素、苯二甲酸等8种活性成分为肿节风的主要药效物质基础;ALB、EGFR、CASP3及MAPK8等为其关键靶点;分子对接验证了大部分关键活性成分能与关键靶点紧密结合;肿瘤、心血管及消化系统疾病是其主要针对的疾病.靶点富集到92个GO条目和43个KEGG通路上,功能涉及激素相关通路、VEGF信号通路和血小板功能等.结论:本研究运用网络药理学方法探究了肿节风的药效物质基础及其多维药理作用机制,为推广其临床应用和进一步的研究提供了思路.