胃癌新辅助化疗耐药机制及治疗策略研究

目的 利用生物信息学筛选影响胃癌化疗耐药的特征基因,深入探讨化疗耐药的分子机制,为胃癌的化疗提供新策略。方法 在GEO数据库筛选胃癌DCS方案（多西他赛+顺铂+替吉奥）耐药表达谱芯片,利用GEO2R工具筛选胃癌耐药组织特征基因;构建差异基因的蛋白质-蛋白质相互作用（protein-protein interaction,PPI）网络;并分析PPI网络的关键节点和稳定模块,进而对差异基因和关键节点及模块基因进行功能富集及注释;再对差异基因进行化合物靶点模拟,筛选出潜在药物。结果 筛得胃癌化疗耐药差异基因共609个,构建PPI网络的关键节点为ACLY和AKT1。差异基因GO功能富集与KEGG通路富集结果显示,主要集中在免疫及肿瘤生长相关通路。C-MAP分析结果提示7个候选化合物吻合度评分>0.9。结论 本研究利用生物信息学筛选了影响胃癌化疗耐药的特征基因,深入探讨化疗耐药的分子机制,为胃癌的化疗提供了新策略。     

Characteristics of children and adolescents first prescribed proton pump inhibitors or histamine-2-receptor antagonists: an observational cohort study

Objective: To describe the characteristics of pediatric patients prescribed proton pump inhibitors (PPIs) vs those of pediatric patients prescribed histamine-2-receptor antagonists (H₂RAs).

Methods: Observational studies were conducted using The Health Improvement Network (THIN) and the PHARMO Database Network. Patients aged 0–18 years who were first prescribed a PPI or H₂RA between October 1, 2009 and September 30, 2012 (THIN) or between September 1, 2008 and August 31, 2011 (PHARMO) were included. Patient characteristics were identified and compared between the PPI and H₂RA cohorts using odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age and sex.

Results: The mean age (years) was higher in the PPI than in the H₂RA cohorts (THIN 12.3 [n?=?8204] vs 5.4 [n?=?7937], PHARMO 11.0 [n?=?15 362] vs 7.1 [n?=?6168]). Previous respiratory disease was more common in the PPI than in the H₂RA cohort in THIN (OR?=?1.19, 95% CI?=?1.08–1.30), as were asthma and respiratory medication use in PHARMO (OR?=?1.27, 95% CI?=?1.12–1.45 and OR?=?1.23, 95% CI?=?1.10–1.38, respectively) and oral corticosteroid use in both databases (OR?=?1.45, 95% CI?=?1.10–1.92 [THIN]; OR?=?2.80, 95% CI?=?2.11–3.71 [PHARMO]). Non-steroidal anti-inflammatory drugs, antibiotics, and oral contraceptives were also more common in PPI than in H₂RA cohorts in both databases.

Conclusions: Pediatric patients receiving PPIs and those receiving H₂RAs may represent different patient populations. PPIs may be more commonly prescribed than H₂RAs among patients with respiratory diseases.     

基于生物信息学分析阿尔茨海默病相关多脑区免疫机制及治疗中药预测

目的 利用生物信息学技术筛选阿尔茨海默病（AD）不同脑区差异表达基因,探讨各脑区的免疫机制,以预测潜在的治疗中药。方法 从 GEO数据库获得 AD的样本数据,进行差异表达基因（DEGs）分析及加权基因共表达网络分析（WGCNA）,对各脑区最相关的模块进行蛋白质-蛋白质相互作用（PPI）网络分析获得核心基因,并使用受试者工作特征曲线（ROC）曲线评估其诊断价值。对差异基因进行免疫通路富集分析,并使用 CIBERSORT算法分析免疫细胞浸润模式,通过 Coremine Medical筛选治疗 AD的潜在中药。结果 大脑的内嗅皮层（EC）区有 3 280个差异基因、海马体（HIP）区有 1 591个差异基因、内侧颞回（MTG）区有 3 995个差异基因、后扣带（PC）区有 2 056个差异基因、额上回（SFG）区有907个差异基因、初级视觉皮层（VCX）区有1 480个差异基。其中EC与VCX区与blue模块相关性高、HIP与PC区与turquoise模块相关性高、MTG、SFG别与绿色和黄色模块相关性高。PPI网络显示 EC区有 4个 Hub基因,HIP区有 13个Hub基因,MTG区有 4个 Hub基因,PC区有 9个 Hub基因,SFG区有 17个 Hub基因,VCX区有 13个 Hub基因。不同脑区富集有不同免疫通路的模块。通过基因映射到姜黄为治疗 AD的潜在中药,其映射到 EP300、PPARG、CCND1、GSK3B、BCL2、EGFR、KDR、MYC和IL1B等基因上。结论 AD患者在不同脑区表现出多样化的免疫途径,这种差异与AD发病机制紧密相连。姜黄有望作为治疗AD的潜在中药。     

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Introduction: Proton Pump inhibitors (PPIs) are commonly used for a variety of acid related disorders. Despite the overall effectiveness and safety profile of PPIs, some patients do not respond adequately or develop treatment related adverse events. This variable response among patients is in part due to genotype variability of CYP2C19, the gene encoding the CYP450 (CYP2C19) isoenzyme responsible for PPIs metabolism.

Areas covered: This article provides an overview of the pharmacokinetics and mechanism of action of the currently available PPIs, including the magnitude of CYPC19 contribution to their metabolism. Additionally, the role of CYP2C19 genetic variability in the therapeutic effectiveness or outcomes of PPI therapy is highlighted in details, to provide supporting evidence for the potential value of CYP2C19 genotype-guided approaches to PPI drug therapy.

Expert opinion: There is a large body of evidence describing the impact of CYP2C19 variability on PPIs and its potential role in individualizing PPI therapy, yet, CYP2C19 pharmacogenetics has not been widely implemented into clinical practice. More data are needed but CYP2C19 genotype-guided dosing of PPIs is likely to become increasingly common and is expected to improve clinical outcomes, and minimize side effects related to PPIs.     

The protective effect of Hypericum connatum on stress-induced escape deficit in rat is related to its flavonoid content

Context Hypericum perforatum L. (Hypericaceae), used in moderate depression treatment, is active in experimental tests for antidepressant activity. For H. connatum Lam., a South American species lacking hyperforin, antidepressant effects have not been demonstrated.

Objective This study evaluates the antidepressant-like effect of H. connatum in rats and identifies the components involved in this activity.

Materials and methods First, the effects of acute and 14-d oral administrations of an extract derived from H. connatum aerial parts were studied using the Escape Deficit (ED) test. Next, methanol-extracted flavonoid-enriched fractions B and C and fraction-purified flavonoids (quercetin, rutin and isoquercitrin) were evaluated in the ED test after acute administration. To rule out possible confounding effects of the flavonoids, we examined nociceptive threshold using the tail-flick test and anxious behaviour using the elevated plus maze (EPM) test.

Results Hypericum connatum increased reactivity of unavoidable stress-exposed rats after acute (0.5 and 1?g/kg: ED?=?18.6/30 and 19.8/30, respectively) and repeated administration (0.5?g/kg twice daily: ED?=?17.8/30). Protective effects were observed for fractions B and C (250?mg/kg: ED?=?18.1/30 and 18.8/30, respectively), quercetin (2.5, 5 and 10?mg/kg: ED?=?15.3/30, 18.3/30 and 21.6/30, respectively), rutin (5 and 10?mg/kg: ED?=?15.4/30 and 13.0/30, respectively) and isoquercitrin (2.5?mg/kg: ED?=?19.2/30). The flavonoids did not modify nociceptive threshold or performance in the EPM test.

Discussion and conclusion Hypericum connatum showed protective activity in the ED test, a correlate of potential antidepressant-like effects that appeared to be related to the flavonoid components of this species.     

Prognostic importance of the albumin to globulin ratio in metastatic gastric cancer patients

Aim: The aim of this study was to evaluate the prognostic importance of the albumin to globulin ratio (AGR) in terms of overall survival (OS) and progression free survival (PFS) in metastatic gastric cancer patients.

Methods: The patients diagnosed with metastatic gastric cancer between 2009 and April 2016 at the hospital have been studied retrospectively. The clinicopathological characteristics, laboratory, and treatment parameters have been assessed. AGR value has been calculated using the following formula (AGR?=?serum albumin/total protein???serum albumin).

Results: In total, 251 patients were included in the study population. The median value of AGR was 1.206 (range?=?0.460–3.130), and the cut-off value was set as 1.20. Based on the cut-off value, 126 patients were categorized in the low AGR group, while the remaining 125 patients were categorized in the high AGR group. ECOG (Eastern Cooperative Oncology Group) performance scores, CEA levels, CA19-9 levels, hemoglobin levels, lactate dehydrogenase levels, and liver metastasis ratios varied significantly between the low and high AGR groups (p?<?.05). The Kaplan-Meier curve has shown that, compared to the low AGR group, the high AGR group has better OS (12.2 vs 9.3 months, p?=?.002) and better PFS (8.0 vs 5.7 months, p?<?.001) rates. The univariate and multivariate analyses also proved that low AGR is an independent bad risk factor in metastatic gastric cancer patients, both in terms of OS (p?=?.019, Hazard Ratio (HR)?=?1.380, 95% Confidence Interval (CI)?=?1.055–1.805) and PFS (p?=?.002, HR?=?1.514, 95% CI?=?1.164–1.968).

Conclusion: In metastatic gastric cancer patients, AGR is an independent prognostic factor for OS and PFS. Thus, in this patient group, the low cost albumin and globulin which can be measured with routine clinical practice may be used as an appropriate prognostic tool.     

Indications and safety of proton pump inhibitor drug use in patients with cancer

Introduction: Although the exact prevalence of proton pump inhibitor (PPI) use in cancer patients is not known, it is generally perceived to be widespread. PPIs are generally well tolerated and carry an excellent safety profile. However, increasing and longer term PPI use has raised concerns about the risk of pneumonia, bone fractures and enteric infections, and a possible interaction with clopidogrel that could increase the risk of cardiovascular events.

Areas covered: We conducted a PubMed search of English language articles addressing the safety and adverse events associated with PPI use with particular emphasis in cancer patients.

Expert opinion: PPIs, frequently used in cancer patients, are generally well tolerated and carry an excellent safety profile. PPI-induced acid suppression may increase the risk of Clostridium difficile or other enteric infections, nutritional deficiencies and community acquired pneumonia, all particularly important in cancer patients. The indications for PPI use in cancer patients should be carefully reviewed prior to use.     

Utilization and safety of proton-pump inhibitors and histamine-2 receptor antagonists in children and adolescents: an observational cohort study

Background: Little is known about the use of acid-suppressing treatments and related safety events in children.

Objective: This study compared patient characteristics and safety outcomes among children prescribed acid-suppressing drugs for the first time.

Methods: The Health Improvement Network was used to determine the characteristics of children prescribed a proton pump inhibitor (PPI; esomeprazole or another PPI) or a histamine-2 receptor antagonist (H₂RA) by UK primary care physicians between October 2009 and September 2012. Pre-defined safety outcomes were compared among the treatment groups in up to 18 months of follow-up.

Results: The cohorts comprised 8,172 patients on PPIs (including 24 patients on esomeprazole) and 7,905 on H₂RAs. The baseline characteristics were similar between cohorts, although the children in the PPI cohorts tended to be older. No safety outcomes occurred in the esomeprazole cohort. In the other-PPIs cohort, 92 safety outcomes occurred, most commonly gastroenteritis (n?=?36; 39.1%). In the H₂RAs cohort, 193 safety outcomes occurred, most commonly gastroenteritis (n?=?62; 32.1%). The incidence of most safety outcomes was higher in the H₂RAs cohort than in the other-PPIs cohort, including failure to thrive (3.11 [95% confidence interval (CI)?=?2.25–4.28] vs 0.49 per 1,000 person-years [95% CI?=?0.22–1.07]) and gastroenteritis (5.27 [95% CI?=?4.11–6.75] vs 3.04 per 1,000 person-years [95% CI?=?2.20–4.20]).

Conclusion: Esomeprazole is rarely prescribed to children when they first require acid-suppressing medication, compared with other PPIs/H₂RAs. Overall, more safety outcomes occurred in the H₂RAs cohort than in the PPI cohorts.     

Quercetin nanoparticles alter pharmacokinetics of bromocriptine,reflecting its enhanced inhibitory action on liver and intestinal CYP 3A enzymes in rats

1.?Quercetin is a dietary flavonoid has extremely low water solubility and found to possess CYP3A inhibitory activity. The purpose of the present study was to evaluate the effect of quercetin and quercetin nanoparticles (NQC) on the pharmacokinetics of bromocriptine (BRO) in rats.

2.?NQC prepared by antisolvent precipitation method and characterized by SEM and dissolution test. The following methods were used in this study i.e. in vitro liver and intestinal CYP3A microsomal activity and in vitro non-everted sac method. To confirm these findings, an in vivo pharmacokinetic study was also performed.

3.?The results indicate that quercetin significantly (p?P_app of BRO were significantly increased in NQC and quercetin groups. Furthermore, in vivo study revealed that the increased levels of C_max and AUC were comparatively high in NQC pretreated group than quercetin group. In addition, pretreatment with quercetin and NQC significantly (p?4.?NQC pretreatment might be result in higher plasma levels of quercetin that could inhibit the CYP3A enzyme and enhanced the bioavailability of BRO.     

Efficacy and safety of ultrasound-guided percutaneous polidocanol sclerotherapy in benign predominantly cystic thyroid nodules: a prospective study

Objective: To evaluate the efficacy and safety of percutaneous polidocanol injection (PPI) in treatment of predominantly cystic thyroid nodules.

Materials and methods: This prospective study included 111 patients with 122 benign predominantly cystic thyroid nodules inducing pressure symptoms or cosmetic problems. The nodules were randomized to a single aspiration with (n?=?61) or without (n?=?61) subsequent PPI and followed up after 1, 3, 6, and 12 months. Ten patients (12 nodules) declined to follow up after aspiration in group 2. Nodule volumes, symptoms scores, and cosmetic scores were evaluated before and after treatment. The therapeutic success rate and safety of PPI for treatment of predominantly cystic thyroid nodules were also evaluated.

Results: In the PPI group, the nodule volumes were reduced from 13.67?±?9.90 to 2.60?±?2.66 (p?50%) was obtained in 57 of 61 (93.44%) nodules in the PPI group, compared to seven of 49 (14.29%) in the aspiration group (p?p?p?p?Conclusions: US-guided PPI of benign recurrent predominantly cystic thyroid nodules is effective and safe. PPI is an important alternative to benign recurrent predominantly cystic thyroid nodules.     

Identification of the collagen family as prognostic biomarkers and immune-associated targets in gastric cancer

BackgroundGastric cancer has extremely high morbidity and mortality. Currently, it is lack of effective biomarkers and therapeutic targets for guiding clinical treatment. In this study, we aimed to identify novel biomarkers and therapeutic targets for gastric cancer.MethodsDifferentially expressed genes (DEGs) between gastric cancer and normal tissues were obtained from Gene Expression Omnibus (GEO). Core genes were identified by constructing protein-protein interaction network of DEGs. The expression of core genes was verified in Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN and clinical samples. Further, the mutation, DNA methylation, prognostic value, and immune infiltration of core genes were validated by cBioPortal, MethSurv, Kaplan-Meier plotter, and Tumor Immune Estimation Resource (TIMER) databases. Additionally, drug response analysis was performed by Cancer Therapy Response Portal (CTRP).ResultsA total of seven collagen family members were identified as core genes among upregulated genes. And copy number amplification may be involved in the upregulation of COL1A1 and COL1A2. Importantly, the collagen family was associated with the poor prognosis of patients with metastasis. Among them, COL1A1 had a higher hazard ratio (HR) for overall survival than other members (HR = 2.33). The correlation between DNA methylation levels at CpG sites of collagen family members and the prognosis was verified in gastric cancer. Besides, collagen family expression was positively correlated with macrophages infiltration and the expression of M2 macrophages markers. Further, collagen expression was related to the sensitivity and resistance of gastric cancer cell lines to certain drugs.ConclusionsThe collagen family, especially COL1A1, COL1A2, and COL12A1, may act as potential prognostic biomarkers and immune-associated therapeutic targets in gastric cancer.     

基于网络药理学和实验验证探讨胃复方对胃癌的效应及作用机制★

目的 基于网络药理学探究胃复方治疗胃癌的作用机制。方法 应用中药系统药理学数据库及分析平台、DrugBank、GeneCards等数据库检索胃复方所含12味中药的有效化学成分及治疗胃癌的潜在靶点，将潜在靶点导入DAVID数据库进行基因本体论（GO）及京都基因与基因组百科全书（KEGG）分析，筛选出潜在的生物过程和涉及的信号通路。采用CCK-8及Western blotting对KEGG分析富集程度最大的信号通路进行验证。结果 胃复方治疗胃癌可能涉及以槲皮素、木樨草素为代表的88种有效活性成分，可能作用于以TP53、STAT3、Akt为代表的194个靶点。GO分析涉及148个生物过程，KEGG分析筛选出PI3K/Akt、TNF、HIF-1等信号通路。体外实验证实胃复方提取物可抑制人胃癌细胞HGC-27增殖，降低其p-PI3K、PI3K、p-Akt、Akt蛋白表达水平；而对于人正常胃黏膜上皮细胞GES-1，胃复方提取物可促进其增殖，上调其p-PI3K、PI3K、p-Akt、Akt蛋白表达。结论 本研究初步预测了胃复方治疗胃癌“中药-多成分-多靶点-多通路”的调控网络，并验证了胃复方提取物可能通过抑制PI3K/Akt信号通路相关蛋白的表达发挥抑制胃癌细胞增殖的作用，证明了网络药理学技术挖掘胃复方具有一定的可信度，但同时兼有不全面性，为进一步探索胃复方的作用机制奠定了基础。     

Genetic association of aromatic hydrocarbon receptor (AHR) and cytochrome P450, family 1, subfamily A,polypeptide 1 (CYP1A1) polymorphisms with dioxin blood concentrations among pregnant Japanese women

Dioxins are metabolized by cytochrome P450, family 1 (CYP1) via the aromatic hydrocarbon receptor (AHR). We determined whether different blood dioxin concentrations are associated with polymorphisms in AHR (dbSNP ID: rs2066853), AHR repressor (AHRR; rs2292596), CYP1 subfamily A polypeptide 1 (CYP1A1; rs4646903 and rs1048963), CYP1 subfamily A polypeptide 2 (CYP1A2; rs762551), and CYP1 subfamily B polypeptide 1 (CYP1B1; rs1056836) in pregnant Japanese women. These six polymorphisms were detected in 421 healthy pregnant Japanese women. Differences in dioxin exposure concentrations in maternal blood among the genotypes were investigated. Comparisons among the GG, GA, and AA genotypes of AHR showed a significant difference (genotype model: P = 0.016 for the mono-ortho polychlorinated biphenyl concentrations and toxicity equivalence quantities [TEQs]). Second, we found a significant association with the dominant genotype model ([TT + TC] vs. CC: P = 0.048 for the polychlorinated dibenzo-p-dioxin TEQs; P = 0.035 for polychlorinated dibenzofuran TEQs) of CYP1A1 (rs4646903). No significant differences were found among blood dioxin concentrations and polymorphisms in AHRR, CYP1A1 (rs1048963), CYP1A2, and CYP1B1. Thus, polymorphisms in AHR and CYP1A1 (rs4646903) were associated with maternal dioxin concentrations. However, differences in blood dioxin concentrations were relatively low.     

Effect of 24 cytochrome P450 2D6 variants found in the Chinese population on the N-demethylation of amitriptyline in vitro

Context: Amitriptyline (AT), one of the tricyclic antidepressants, is still widely used for the treatment of the depression and control of anxiety states and panic disorders in the developing countries.

Objective: This study evaluates the catalytic activities of CYP2D6*1, CYP2D6*2, CYP2D6*10 and 22 novel alleles in Han Chinese population and their effects on the N-demethylation of AT in vitro.

Materials and methods: CYP2D6*1 and 24 CYP2D6 allelic variants were highly expressed in insect cells, and all variants were characterized using AT as a substrate. Reactions were performed at 37?°C with 10–1000?μM substrate for 30?min. We established a HPLC method to quantify the levels of nortriptyline (NT). The kinetic parameters K_m, V_max and intrinsic clearance (V_max/K_m) of NT were calculated.

Results: Among the 24 CYP2D6 variants, all variants exhibited decreased intrinsic clearance values compared with wild-type CYP2D6.1. Kinetic parameters of two CYP2D6 variants (CYP2D6*92, *96) could not be determined because of absent enzyme activities.

Conclusions: The comprehensive in vitro assessment of CYP2D6 variants provides significant insight into allele-specific activity towards AT in vivo.     

基于网络药理学的人参治疗非酒精性脂肪肝病靶点研究

目的 基于网络药理学研究人参对非酒精性脂肪肝病（NAFLD）的治疗靶点。方法 利用网络药理学分析平台BATMAN-TCM获取人参活性成分及其对应靶点,使用Cytoscape软件对功能组-靶点基因-人参药物成分网络进行构建。对靶基因通过STRING平台构建出靶点群蛋白互作网络（protein protein interaction network,PPI）,通过在线工具metascape对靶基因进行通路富集分析。从高通量基因表达数据库（Gene Expression Omnibus,GEO）下载人NAFLD转录组表达数据GSE89632,表达量进行标准化处理,使用双侧非配对t检验来检测表达差异的显著性。结果 人参药物成分对脂肪代谢有显著影响,特别是脂肪酸降解。通过蛋白相互作用分析和通路富集分析,发现了31个人参药物成分的关键靶基因（ACADM、SCD、ACACA、ACSL1、NR1H3、LEP、PPARA、ADIPOQ、NR1H4、CEBPA、HMGCR、SREBF1、TNF、SREBF2、ESR1、ABCA1、INS、AKT1、AVP、RXRA、HSD17B6、SRD5A2、UGT1A1、CYP19A1、PTGS2、CYP2E1、HTR2A、HSD17B1、EDN1、CCL5、AGTR1）和NAFLD发病过程紧密相关。其中胰岛素（insulin,INS）的节点数量远高于其他靶基因,INS的mRNA表达量在NAFLD组织中显著上调（P<0.000 1）。结论 INS可能是人参治疗NAFLD的关键核心靶点之一。     

Recent advances in protein–protein interaction prediction: experimental and computational methods

Introduction: Proteins within the cell act as part of complex networks, which allow pathways and processes to function. Therefore, understanding how proteins interact is a significant area of current research.

Areas covered: This review aims to present an overview of key experimental techniques (yeast two-hybrid, tandem affinity purification and protein microarrays) used to discover protein–protein interactions (PPIs), as well as to briefly discuss certain computational methods for predicting protein interactions based on gene localization, phylogenetic information, 3D structural modeling or primary protein sequence data. Due to the large-scale applicability of primary sequence-based methods, the authors have chosen to focus on this strategy for our review. There is an emphasis on a recent algorithm called Protein Interaction Prediction Engine (PIPE) that can predict global PPIs. The readers will discover recent advances both in the practical determination of protein interaction and the strategies that are available to attempt to anticipate interactions without the time and costs of experimental work.

Expert opinion: Global PPI maps can help understand the biology of complex diseases and facilitate the identification of novel drug target sites. This study describes different techniques used for PPI prediction that we believe will significantly impact the development of the field in a new future. We expect to see a growing number of similar techniques capable of large-scale PPI predictions.     

基于网络药理学和分子对接技术的热毒宁注射液抗SARS、MERS和COVID-19的潜在共性作用机制与活性成分研究

目的 采用网络药理学与分子对接技术探讨热毒宁注射液抗严重急性呼吸综合征（SARS）、中东呼吸综合征（MERS）和新型冠状病毒肺炎（COVID-19）的潜在共性作用机制与活性成分。方法 利用中药系统药理学数据库和分析平台（TCMSP）数据库检索热毒宁注射液中青蒿、金银花、栀子的主要化学成分及其作用靶点。运用UniProt数据库查询相关靶点对应的基因，通过Cytoscape 3.8.2构建中药材-化合物-靶点（基因）网络；在GeneCards数据库中搜集“COVID-19”“SARS”和“MERS”相关靶点，通过Venny 2.1.0数据库映射筛选出3种冠状病毒感染疾病的共有靶点；将SARS、MERS和COVID-19的共有靶点与热毒宁注射液化合物靶点进行交集筛选出共同靶点作为研究靶点；将共同靶点导入STRING数据库获取数据后，使用Cytoscape 3.8.2软件构建蛋白质-蛋白质相互作用（PPI）的网络图；利用R语言进行基因本体论（GO）生物学功能富集分析及京都基因和基因组百科全书（KEGG）信号通路富集分析，绘制柱状图及气泡图进行可视化分析，并构建成分-靶点-通路网络图；选取成分-靶点-通路网络中关键化合物与重要靶点蛋白及新型冠状病毒（SARS-CoV-2）3CL水解酶、血管紧张素转化酶II（ACE2）进行分子对接。结果 热毒宁注射液筛选得到31个活性化合物中，207个相应作用靶点；SARS相关靶点2 453个，MERS相关靶点805个，COVID-19相关靶点2 571个，3种疾病共有靶点786个，与热毒宁注射液的共同靶点11个，分别为HSPA5、CRP、MAPK1、HMOX1、TGFB1、HSP90AA1、TP53、DPP4、CXCL10、PLAT、PRKACA。GO功能富集分析得到生物进程（BP） 995个，分子功能（MF） 71种，细胞组分（CC）31种。KEGG通路富集分析筛选得到99条信号通路（P＜0.05），主要涉及前列腺癌、流体剪切应力和动脉粥样硬化、肝细胞癌、癌症中的蛋白多糖、脂质与动脉粥样硬化、人类T细胞白血病病毒1型感染、MAPK信号通路等。分子对接结果显示热毒宁注射液中槲皮素、木犀草素、山柰酚3种核心活性黄酮类化合物与关键靶点MAPK1、PRKACA、HSP90AA1具有很好的亲和力，并且3种活性化合物与SARS-CoV-2 3CL水解酶及ACE2结合能较推荐化学药小。结论 热毒宁注射液对SARS、MERS和COVID-19 3种疾病具有潜在共性作用，该作用可能与活性化合物槲皮素、木犀草素、山柰酚等作用于MAPK1、PRKACA、HSP90AA1等靶点，调节多种信号通路发挥抑制炎症风暴、调节免疫功能、抗病毒等作用有关。