Automatic Extraction of Medical Latent Variables from ECG Signals Utilizing a Mutual Information-Based Technique and Capsular Neural Networks for Arrhythmia Detection

From a medical perspective,the 12 leads of the heart in an electrocardiogram(ECG)signal have functional dependencies with each other.Therefore,all these leads report different aspects of an arrhythmia.Their differences lie in the level of highlighting and displaying information about that arrhythmia.For example,although all leads show traces of atrial excitation,this function is more evident in lead II than in any other lead.In this article,a new model was proposed using ECG functional and structural dependencies between heart leads.In the prescreening stage,the ECG signals are segmented from the QRS point so that further analyzes can be performed on these segments in a more detailed manner.The mutual information indices were used to assess the relationship between leads.In order to calculate mutual information,the correlation between the 12 ECG leads has been calculated.The output of this step is a matrix containing all mutual information.Furthermore,to calculate the structural information of ECG signals,a capsule neural network was implemented to aid physicians in the automatic classification of cardiac arrhythmias.The architecture of this capsule neural network has been modified to perform the classification task.In the experimental results section,the proposed model was used to classify arrhythmias in ECG signals from the Chapman dataset.Numerical evaluations showed that this model has a precision of 97.02%,recall of 96.13%,F1-score of 96.57%and accuracy of 97.38%,indicating acceptable performance compared to other state-of-the-art methods.The proposed method shows an average accuracy of 2%superiority over similar works.

Automatic modulation recognition of radiation source signals based on two-dimensional data matrix and improved residual neural network

Automatic modulation recognition(AMR)of radiation source signals is a research focus in the field of cognitive radio.However,the AMR of radiation source signals at low SNRs still faces a great challenge.Therefore,the AMR method of radiation source signals based on two-dimensional data matrix and improved residual neural network is proposed in this paper.First,the time series of the radiation source signals are reconstructed into two-dimensional data matrix,which greatly simplifies the signal preprocessing process.Second,the depthwise convolution and large-size convolutional kernels based residual neural network(DLRNet)is proposed to improve the feature extraction capability of the AMR model.Finally,the model performs feature extraction and classification on the two-dimensional data matrix to obtain the recognition vector that represents the signal modulation type.Theoretical analysis and simulation results show that the AMR method based on two-dimensional data matrix and improved residual network can significantly improve the accuracy of the AMR method.The recognition accuracy of the proposed method maintains a high level greater than 90% even at -14 dB SNR.

For LEO Satellite Networks: Intelligent Interference Sensing and Signal Reconstruction Based on Blind Separation Technology

In LEO satellite communication networks,the number of satellites has increased sharply, the relative velocity of satellites is very fast, then electronic signal aliasing occurs from time to time. Those aliasing signals make the receiving ability of the signal receiver worse, the signal processing ability weaker,and the anti-interference ability of the communication system lower. Aiming at the above problems, to save communication resources and improve communication efficiency, and considering the irregularity of interference signals, the underdetermined blind separation technology can effectively deal with the problem of interference sensing and signal reconstruction in this scenario. In order to improve the stability of source signal separation and the security of information transmission, a greedy optimization algorithm can be executed. At the same time, to improve network information transmission efficiency and prevent algorithms from getting trapped in local optima, delete low-energy points during each iteration process. Ultimately, simulation experiments validate that the algorithm presented in this paper enhances both the transmission efficiency of the network transmission system and the security of the communication system, achieving the process of interference sensing and signal reconstruction in the LEO satellite communication system.

HQNN-SFOP:Hybrid Quantum Neural Networks with Signal Feature Overlay Projection for Drone Detection Using Radar Return Signals-A Simulation

With the wide application of drone technology,there is an increasing demand for the detection of radar return signals from drones.Existing detection methods mainly rely on time-frequency domain feature extraction and classical machine learning algorithms for image recognition.This method suffers from the problem of large dimensionality of image features,which leads to large input data size and noise affecting learning.Therefore,this paper proposes to extract signal time-domain statistical features for radar return signals from drones and reduce the feature dimension from 512×4 to 16 dimensions.However,the downscaled feature data makes the accuracy of traditional machine learning algorithms decrease,so we propose a new hybrid quantum neural network with signal feature overlay projection(HQNN-SFOP),which reduces the dimensionality of the signal by extracting the statistical features in the time domain of the signal,introduces the signal feature overlay projection to enhance the expression ability of quantum computation on the signal features,and introduces the quantum circuits to improve the neural network’s ability to obtain the inline relationship of features,thus improving the accuracy and migration generalization ability of drone detection.In order to validate the effectiveness of the proposed method,we experimented with the method using the MM model that combines the real parameters of five commercial drones and random drones parameters to generate data to simulate a realistic environment.The results show that the method based on statistical features in the time domain of the signal is able to extract features at smaller scales and obtain higher accuracy on a dataset with an SNR of 10 dB.On the time-domain feature data set,HQNNSFOP obtains the highest accuracy compared to other conventional methods.In addition,HQNN-SFOP has good migration generalization ability on five commercial drones and random drones data at different SNR conditions.Our method verifies the feasibility and effectiveness of signal detection methods based on quantum computation and experimentally demonstrates that the advantages of quantum computation for information processing are still valid in the field of signal processing,it provides a highly efficient method for the drone detection using radar return signals.

Comparative study of anti-inflammatory effects of different processed products through the COX-2/PGE2 signaling pathway: based on network pharmacology and molecular docking

Background:Radix Aconiti Lateralis Preparata(Fu-zi)is a traditional Chinese medicinal herb,which has been widely used in the clinic and has potent anti-inflammatory activities.we aimed to explore the mechanisms of extract containing alkaloids from different Fu-zi Processed Products(FPP)in treating inflammation,especially rheumatoid arthritis(RA).Methods:Firstly,using network pharmacology technology,the ingredients,and targets of Fu-zi were obtained by searching and screening,the targets involving RA were acquired,the intersection targets were constructed a"component-target-pathway"network.A comprehensive investigation was conducted on the anti-rheumatoid arthritis mechanisms of 5 FPPs in lipopolysaccharide(LPS)induced RAW264.7 cells,which serve as a model for RA.The production of NO and inflammatory cytokines were measured by ELISA kit.Quantitative Real-time PCR(qRT-PCR)was utilized to measure the mRNA levels.COX-2/PGE2 signaling pathway-associated proteins were determined by western blot.Results:According to a network pharmacological study,16 chemical components and 43 common targets were found in Fu-zi and 6 key targets including PTGS2 were closely related to the mechanism of Fu-zi in treating RA.The in vitro study revealed that the levels of NO,TNF-α,and IL-1βwere substantially decreased by the 5 FPPs.The 5 FPPs significantly suppressed the expression of proteins COX-2,iNOS,and NF-κB,with particularly notable effects observed for PFZ and XFZ.Conclusion:Altogether,these results demonstrated that the 5 PPS containing alkaloids have a good anti-RA-related inflammatory effect,and the mechanism may be related to COX-2/PGE2 signaling pathway,particularly,Fu-zi prepared utilizing a traditional Chinese technique.

Zuo Gui Wan Promotes Osteogenesis via PI3K/AKT Signaling Pathway:Network Pharmacology Analysis and Experimental Validation

Objective Osteogenesis is vitally important for bone defect repair,and Zuo Gui Wan(ZGW)is a classic prescription in traditional Chinese medicine(TCM)for strengthening bones.However,the specific mechanism by which ZGW regulates osteogenesis is still unclear.The current study is based on a network pharmacology analysis to explore the potential mechanism of ZGW in promoting osteogenesis.Methods A network pharmacology analysis followed by experimental validation was applied to explore the potential mechanisms of ZGW in promoting the osteogenesis of bone marrow mesenchymal stem cells(BMSCs).Results In total,487 no-repeat targets corresponding to the bioactive components of ZGW were screened,and 175 target genes in the intersection of ZGW and osteogenesis were obtained.And 28 core target genes were then obtained from a PPI network analysis.A GO functional enrichment analysis showed that the relevant biological processes mainly involve the cellular response to chemical stress,metal ions,and lipopolysaccharide.Additionally,KEGG pathway enrichment analysis revealed that multiple signaling pathways,including the phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)signaling pathway,were associated with ZGW-promoted osteogensis.Further experimental validation showed that ZGW could increase alkaline phosphatase(ALP)activity as well as the mRNA and protein levels of ALP,osteocalcin(OCN),and runt related transcription factor 2(Runx 2).What’s more,Western blot analysis results showed that ZGW significantly increased the protein levels of p-PI3K and p-AKT,and the increases of these protein levels significantly receded after the addition of the PI3K inhibitor LY294002.Finally,the upregulated osteogenic-related indicators were also suppressed by the addition of LY294002.Conclusion ZGW promotes the osteogenesis of BMSCs via PI3K/AKT signaling pathway.

Detection of healthy and pathological heartbeat dynamics in ECG signals using multivariate recurrence networks with multiple scale factors

The electrocardiogram(ECG)is one of the physiological signals applied in medical clinics to determine health status.The physiological complexity of the cardiac system is related to age,disease,etc.For the investigation of the effects of age and cardiovascular disease on the cardiac system,we then construct multivariate recurrence networks with multiple scale factors from multivariate time series.We propose a new concept of cross-clustering coefficient entropy to construct a weighted network,and calculate the average weighted path length and the graph energy of the weighted network to quantitatively probe the topological properties.The obtained results suggest that these two network measures show distinct changes between different subjects.This is because,with aging or cardiovascular disease,a reduction in the conductivity or structural changes in the myocardium of the heart contributes to a reduction in the complexity of the cardiac system.Consequently,the complexity of the cardiac system is reduced.After that,the support vector machine(SVM)classifier is adopted to evaluate the performance of the proposed approach.Accuracy of 94.1%and 95.58%between healthy and myocardial infarction is achieved on two datasets.Therefore,this method can be adopted for the development of a noninvasive and low-cost clinical prognostic system to identify heart-related diseases and detect hidden state changes in the cardiac system.

A Distributed Newton Method for Processing Signals Defined on the Large-Scale Networks

In the graph signal processing(GSP)framework,distributed algorithms are highly desirable in processing signals defined on large-scale networks.However,in most existing distributed algorithms,all nodes homogeneously perform the local computation,which calls for heavy computational and communication costs.Moreover,in many real-world networks,such as those with straggling nodes,the homogeneous manner may result in serious delay or even failure.To this end,we propose active network decomposition algorithms to select non-straggling nodes(normal nodes)that perform the main computation and communication across the network.To accommodate the decomposition in different kinds of networks,two different approaches are developed,one is centralized decomposition that leverages the adjacency of the network and the other is distributed decomposition that employs the indicator message transmission between neighboring nodes,which constitutes the main contribution of this paper.By incorporating the active decomposition scheme,a distributed Newton method is employed to solve the least squares problem in GSP,where the Hessian inverse is approximately evaluated by patching a series of inverses of local Hessian matrices each of which is governed by one normal node.The proposed algorithm inherits the fast convergence of the second-order algorithms while maintains low computational and communication cost.Numerical examples demonstrate the effectiveness of the proposed algorithm.

Classification of Electrocardiogram Signals for Arrhythmia Detection Using Convolutional Neural Network

With the help of computer-aided diagnostic systems,cardiovascular diseases can be identified timely manner to minimize the mortality rate of patients suffering from cardiac disease.However,the early diagnosis of cardiac arrhythmia is one of the most challenging tasks.The manual analysis of electrocardiogram(ECG)data with the help of the Holter monitor is challenging.Currently,the Convolutional Neural Network(CNN)is receiving considerable attention from researchers for automatically identifying ECG signals.This paper proposes a 9-layer-based CNN model to classify the ECG signals into five primary categories according to the American National Standards Institute(ANSI)standards and the Association for the Advancement of Medical Instruments(AAMI).The Massachusetts Institute of Technology-Beth Israel Hospital(MIT-BIH)arrhythmia dataset is used for the experiment.The proposed model outperformed the previous model in terms of accuracy and achieved a sensitivity of 99.0%and a positivity predictively 99.2%in the detection of a Ventricular Ectopic Beat(VEB).Moreover,it also gained a sensitivity of 99.0%and positivity predictively of 99.2%for the detection of a supraventricular ectopic beat(SVEB).The overall accuracy of the proposed model is 99.68%.

Intelligent Modulation Recognition of Communication Signal for Next-Generation 6G Networks

In recent years,the need for a fast,efficient and a reliable wireless network has increased dramatically.Numerous 5G networks have already been tested while a few are in the early stages of deployment.In noncooperative communication scenarios,the recognition of digital signal modulations assists people in identifying the communication targets and ensures an effective management over them.The recent advancements in both Machine Learning(ML)and Deep Learning(DL)models demand the development of effective modulation recognition models with self-learning capability.In this background,the current research article designs aDeep Learning enabled Intelligent Modulation Recognition of Communication Signal(DLIMR-CS)technique for next-generation networks.The aim of the proposed DLIMR-CS technique is to classify different kinds of digitally-modulated signals.In addition,the fractal feature extraction process is appliedwith the help of the Sevcik Fractal Dimension(SFD)approach.Then,the extracted features are fed into the Deep Variational Autoencoder(DVAE)model for the classification of the modulated signals.In order to improve the classification performance of the DVAE model,the Tunicate Swarm Algorithm(TSA)is used to finetune the hyperparameters involved in DVAE model.A wide range of simulations was conducted to establish the enhanced performance of the proposed DLIMR-CS model.The experimental outcomes confirmed the superior recognition rate of the DLIMR-CS model over recent state-of-the-art methods under different evaluation parameters.

A Novel Radial Basis Function Neural Network Approach for ECG Signal Classification

ions in the ECG signal.The cardiologist and medical specialistfind numerous difficulties in the process of traditional approaches.The specified restrictions are eliminated in the proposed classifier.The fundamental aim of this work is tofind the R-R interval.To analyze the blockage,different approaches are implemented,which make the computation as facile with high accuracy.The information are recovered from the MIT-BIH dataset.The retrieved data contain normal and pathological ECG signals.To obtain a noiseless signal,Gaborfilter is employed and to compute the amplitude of the signal,DCT-DOST(Discrete cosine based Discrete orthogonal stock well transform)is implemented.The amplitude is computed to detect the cardiac abnormality.The R peak of the underlying ECG signal is noted and the segment length of the ECG cycle is identified.The Genetic algorithm(GA)retrieves the primary highlights and the classifier integrates the data with the chosen attributes to optimize the identification.In addition,the GA helps in performing hereditary calculations to reduce the problem of multi-target enhancement.Finally,the RBFNN(Radial basis function neural network)is applied,which diminishes the local minima present in the signal.It shows enhancement in characterizing the ordinary and anomalous ECG signals.

Simiao Wan alleviates obesity-associated insulin resistance via PKCε/IRS-1/PI3K/Akt signaling pathway based on network pharmacology analysis and experimental validation

Background:The purpose of the study was to investigatethe active ingredients and potential biochemicalmechanisms of Simiao Wan(SMW)in obesity-associated insulin resistance.Methods:An integrated network pharmacology method to screen the active compoundsand candidate targets,construct the protein-protein-interaction network,and ingredients-targets-pathways network was constructed for topological analysis to identify core targets and main ingredients.To find the possible signaling pathways,enrichment analysis was performed.Further,a model of insulin resistance in HL-7702 cells was established to verify the impact of SMW and the regulatory processes.Results:An overall of 63 active components and 151 candidate targets were obtained,in which flavonoids were the main ingredients.Enrichment analysis indicated that the PI3K-Akt signaling pathway was the potential pathway regulated by SMW in obesity-associated insulin resistance treatment.The result showed that SMW could significantly ameliorate insulin sensitivity,increase glucose synthesis and glucose utilization and reduce intracellular lipids accumulation in hepatocytes.Also,SMW inhibited diacylglycerols accumulation-induced PKCεactivity and decreased its translocation to the membrane.Conclusion:SMW ameliorated obesity-associated insulin resistance through PKCε/IRS-1/PI3K/Akt signaling axis in hepatocytes,providing a new strategy for metabolic disease treatment.

基于CNN-Swin Transformer Network的LPI雷达信号识别

针对在低信噪比(SNR)条件下,低截获概率雷达信号调制方式识别准确率低的问题,提出一种基于Transformer和卷积神经网络(CNN)的雷达信号识别方法。首先,引入Swin Transformer模型并在模型前端设计CNN特征提取层构建了CNN+Swin Transformer网络(CSTN),然后利用时频分析获取雷达信号的时频特征,对图像进行预处理后输入CSTN模型进行训练,由网络的底部到顶部不断提取图像更丰富的语义信息,最后通过Softmax分类器对六类不同调制方式信号进行分类识别。仿真实验表明:在SNR为-18 dB时,该方法对六类典型雷达信号的平均识别率达到了94.26%,证明了所提方法的可行性。

Attention-Based Residual Dense Shrinkage Network for ECG Denoising

Electrocardiogram(ECG)signal is one of the noninvasive physiological measurement techniques commonly usedin cardiac diagnosis.However,in real scenarios,the ECGsignal is susceptible to various noise erosion,which affectsthe subsequent pathological analysis.Therefore,the effective removal of the noise from ECG signals has becomea top priority in cardiac diagnostic research.Aiming at the problem of incomplete signal shape retention andlow signal-to-noise ratio(SNR)after denoising,a novel ECG denoising network,named attention-based residualdense shrinkage network(ARDSN),is proposed in this paper.Firstly,the shallow ECG characteristics are extractedby a shallow feature extraction network(SFEN).Then,the residual dense shrinkage attention block(RDSAB)isused for adaptive noise suppression.Finally,feature fusion representation(FFR)is performed on the hierarchicalfeatures extracted by a series of RDSABs to reconstruct the de-noised ECG signal.Experiments on the MIT-BIHarrhythmia database and MIT-BIH noise stress test database indicate that the proposed scheme can effectively resistthe interference of different sources of noise on the ECG signal.

Damage Diagnosis of Bleacher Based on an Enhanced Convolutional Neural Network with Training Interference

Bleachers play a crucial role in practical engineering applications, and any damage incurred during their operationposes a significant threat to the safety of both life and property. Consequently, it becomes imperative to conductdamage diagnosis and health monitoring of bleachers. The intricate structure of bleachers, the varied types ofpotential damage, and the presence of similar vibration data in adjacent locations make it challenging to achievesatisfactory diagnosis accuracy through traditional time-frequency analysis methods. Furthermore, field environmentalnoise can adversely impact the accuracy of bleacher damage diagnosis. To enhance the accuracy and antinoisecapabilities of bleacher damage diagnosis, this paper proposes improvements to the existing ConvolutionalNeural Network with Training Interference (TICNN). The result is an advanced Convolutional Neural Networkmodel with superior accuracy and robust anti-noise capabilities, referred to as Enhanced TICNN (ETICNN).ETICNN autonomously extracts optimal damage-sensitive features from the original vibration data. To validatethe superiority of the proposed ETICNN, experiments are conducted using the bleacher model from Qatar Universityas the subject. Comparative studies under identical experimental conditions involve TICNN, Deep ConvolutionalNeural Networks with wide first-layer kernels (WDCNN), and One-Dimensional ConvolutionalNeural Network (1DCNN). The experimental findings demonstrate that the ETICNN model achieves the highestaccuracy, approximately 99%, and exhibits robust classification abilities in both Phases I and II of the damagediagnosis experiments. Simultaneously, the ETICNN model demonstrates strong anti-noise capabilities, outperformingTICNN by 3% to 4% and surpassing other models in performance.

Comprehensive Analysis of Gender Classification Accuracy across Varied Geographic Regions through the Application of Deep Learning Algorithms to Speech Signals

This article presents an exhaustive comparative investigation into the accuracy of gender identification across diverse geographical regions,employing a deep learning classification algorithm for speech signal analysis.In this study,speech samples are categorized for both training and testing purposes based on their geographical origin.Category 1 comprises speech samples from speakers outside of India,whereas Category 2 comprises live-recorded speech samples from Indian speakers.Testing speech samples are likewise classified into four distinct sets,taking into consideration both geographical origin and the language spoken by the speakers.Significantly,the results indicate a noticeable difference in gender identification accuracy among speakers from different geographical areas.Indian speakers,utilizing 52 Hindi and 26 English phonemes in their speech,demonstrate a notably higher gender identification accuracy of 85.75%compared to those speakers who predominantly use 26 English phonemes in their conversations when the system is trained using speech samples from Indian speakers.The gender identification accuracy of the proposed model reaches 83.20%when the system is trained using speech samples from speakers outside of India.In the analysis of speech signals,Mel Frequency Cepstral Coefficients(MFCCs)serve as relevant features for the speech data.The deep learning classification algorithm utilized in this research is based on a Bidirectional Long Short-Term Memory(BiLSTM)architecture within a Recurrent Neural Network(RNN)model.

A COMPACT PLANAR ULTRA-BROADBAND SUM-AND-DIFFERENCE NETWORK

In this paper, the design of a planar ultra-broadband sum-and-difference network is presented. This network employs a novel power divider and anti-phase balun as a building block. An equivalent 180° coupler with a bandwidth of 6.2 - 14GHz is achieved by back-connecting the power divider and balun together. Four such couplers are connected to form an ultra-broadband sum-and-difference network which has a bandwidth of 91%. This network, with insertion loss less than 1.8dB in sum port and nulls less than -20dB in all delta ports, is verified to be excellent, resulting in the advantages of being compact, easy manufacturing and low cost.

Action Mechanism of Components from Gardenia jasminoides on Eye Skin Based on Network Pharmacology

[Objectives]To explore the pharmacological effects of Gardenia jasminoides and its potential benefits on eye skin.[Methods]TCMSP and SymMap databases were used to screen the active components and corresponding targets of G.jasminoides.Human eye skin-related targets were screened,and the active component-target network and protein-protein interaction(PPI)network were established.Gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed.[Results]Twenty-six active compounds were screened out from G.jasminoides,and 277 targets were obtained.From the Gencards database,26652 disease targets were retrieved and 205 related gene targets were screened.The active component-action target network of G.jasminoides constructed by Cytoscape software revealed the potential of G.jasminoides to play a role in multiple biological pathways.In addition,PPI-network analysis,GO function analysis and KEGG pathway enrichment analysis revealed that the active components of G.jasminoides mainly regulate the biological processes such as inflammatory response,oxidative stress and apoptosis,involving MAPK,NF-κB and other important signaling pathways.[Conclusions]This study provides a theoretical basis for the eye skin protection of G.jasminoides and an important clue for future drug development.

Integration of network pharmacology and bone marrow mesenchymal stem cells experimental research to reveal the molecular mechanisms for Hai Honghua medicinal liquor against osteoporosis

Background:Hai Honghua medicinal liquor(HHML)formula has been used in clinical practice for a long time,mainly for the treatment of freshly closed fractures,to promote osteogenesis,to increase bone mass,and thus to promote fracture healing.However,the underlying mechanisms of HHML in the treatment of osteoporosis(OP)are still unclear.Methods:Firstly,Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform and The Encyclopedia of Traditional Chinese Medicine were used to screen the targets of the active compounds of HHML.At the same time,OP targets were identified through GeneCards,Online Mendelian Inheritance in Man,DisGeNET,Therapeutic Target Database,Comparative Toxicogenomics Database and Human Phenotype Ontology databases.Next,protein-protein interaction and pathway networks were constructed for compound-disease common targets,and core targets and compounds were screened for molecular docking.Furthermore,rat bone marrow mesenchymal stem cells were extracted as model cells,and the osteogenic effects of HHML were verified via in vitro experiments.Results:Total of 343 common targets of HHML-OP and the top 10 target proteins in the protein-protein interaction network are TP53,AKT1,STAT3,HSP90AA1,ESR1,TNF,IL6,MAPK1,MAPK3 and MAPK8.Enrichment analysis yielded that the key molecular pathway was the PI3K/Akt signaling pathway.Molecular docking analysis showed that baicalein,erysodienone and naringenin docked with the target proteins AKT1,STAT3 and TP53,respectively,with low binding energy and high affinity.In addition,In vitro experiments demonstrated that HHML promoted the proliferation of bone marrow mesenchymal stem cells;compared with the control group,HHML-treated cells showed enhanced alkaline phosphatase staining,promoted the expression of OCN,RUNX2,BSP,and COL1 mRNAs as well as the expression of PI3K and AKT phosphorylated proteins.Secondly,the expression of target proteins revealed that HHML promoted the phosphorylation of STAT3 protein and inhibited the expression of P53.Conclusions:Our study investigated that HHML treatment with OP promotes bone formation possibly through activation of the PI3K/Akt signaling pathway and may involve STAT3 and TP53 target interactions.

Network pharmacology and molecular docking analysis reveal insights into the molecular mechanism of Gualou Qumai Wan in clear cell renal cell carcinoma

Background:To initially clarify the potential therapeutic targets and pharmacological mechanism regarding Gualou Qumai Wan(GQW),a kind of traditional Chinese medicine(TCM),in clear cell renal cell carcinoma(ccRCC)by virtue of the network pharmacology analysis and molecular docking analysis.Methods:The screening of bioactive components and targets of GQW was based on the Traditional Chinese Medicine System Pharmacology(TCMSP)and the UniProt platform served for standardizing their targets.Online Mendelian Inheritance in Man(OMIM),PharmGkb,TTD,DrugBank and GeneCards databases were searched to collect the disease targets of ccRCC.Cytoscape assisted in constructing herb-compound-target(H-C-T)networks.The STRING database was searched for constructing the target protein-protein interaction(PPI)networks,while the R programming language served for analyzing GO functional terms and the KEGG pathways related to potential targets.Analyses of core genes related to survival and tumor microenvironment(TME)were conducted respectively based on the GEPIA2 database and TIMER 2.0 database.Human Protein Atlas(HPA)and The Cancer Genome Atlas(TCGA)helped to obtain core genes’protein expression as well as transcriptome expression level.Autodock Vina software validated the molecular docking regarding GQW components and pivotal targets.Results:The constructed H-C-T networks mainly had 33 compounds and 65 targets.A topological analysis of the PPI network identified that ESR1,AKT1,HIF1A,PTGS2,TP53 and VEGFA serve as core targets in the way GQW affects ccRCC.According to the GO and KEGG pathway enrichment analyses,the effects of GQW are mediated by genes related to hypoxia and oxidative stress as well as the Chemical carcinogenesis-receptor activation and PI3K-Akt signaling pathways.AKT1 shows a close relation to the recruitment of various immune cells and can remarkably affect disease prognosis according to reports.Molecular docking and molecular dynamics simulations showed that diosgenin has higher affinity with core targets.Conclusion:The study makes a comprehensive explanation of the biological activity,potential targets,as well as molecular mechanism regarding GQW against ccRCC,which promisingly assists in revealing the action mechanism of TCM formulae in disease treatment and the respective and scientific basis.