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Fenfen Guo,1 Hong Li,1 Jingjing Wang,1 Jiangfeng Wang,1 Jinling Zhang,1 Fanfang Kong,1 Zemin Zhang,2 Jinbao Zong1 1Departments of Clinical Laboratory, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao, People’s Republic of China; 2Departments of Infectious Disease, Qingdao Women and Children’s Hospital, Qingdao, People’s Republic of ChinaCorrespondence: Jinbao Zong, Email sdjinbaozong@163.comAbstract: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Tumor immune microenvironment (TIME), angiogenesis, epithelial-mesenchymal transformation (EMT), invasion, metastasis, metabolism, and drug resistance are the main factors affecting the development and treatment of tumors. MiRNAs play crucial roles in almost all major cellular biological processes. Studies have been carried out on miRNAs as biomarkers and therapeutic targets. Their dysregulation contributes to the progression and prognosis of HCC. This review aims to explore the molecular cascades and corresponding phenotypic changes caused by aberrant miRNA expression and their regulatory mechanisms, summarize and analyze novel biomarkers from somatic fluids (plasma/serum/urine), and highlight the latent capacity of miRNAs as therapeutic targets.Keywords: hepatocellular carcinoma, microRNAs, regulatory mechanisms, biomarker, targeted therapy

Shiyu Zhang, Fanting Kong, Lei Zheng, Xiaowei Li, Lining Jia, Lixian Yang Department of Breast Surgery, Xingtai People’s Hospital, Xingtai, Hebei, 054000, People’s Republic of ChinaCorrespondence: Lixian Yang, Department of Breast Surgery, Xingtai People’s Hospital, No. 818 Xiangdu District, Xingtai, Hebei, 054000, People’s Republic of China, Email yanglixian@hebmu.edu.cnBackground: The role of Semaphorin 7a (SEMA7A) in the initiation and progression of different types of cancerous lesions has been extensively studied. However, the prognostic significance of SEMA7A, specifically in breast cancer (BC), lacks clarity.Methods: We conducted an evaluation on the relationship between SEMA7A and the prognosis, immune invasion and tumor mutation burden in different types of cancer by analyzing data from The Cancer Genome Atlas database. The present study focused on investigating the expression level, mutation, immune correlation and coexpression of SEMA7A in BC, utilizing various databases such as the University of Alabama at Birmingham Cancer data analysis portal, cBioPortal and tumor immune estimation resource. Survival analysis was carried out using the Kaplan-Meier Plotter. Furthermore, we employed the R software package to generate receiver operating characteristic (ROC) curves and nomograms. Notably, P< 0.05 was considered to indicate statistical significance.Results: Using pancancer analysis, it has been observed that the expression of SEMA7A is elevated in various types of cancer and is strongly correlated with the prognosis of different cancer types. SEMA7A also exhibits a significant association with the tumor mutation burden of diverse types of cancer. Moreover, SEMA7A displays a notable increase in BC cases, and was indicated to have a substantial association with the abundance of immune infiltration. In-depth survival analysis demonstrated that elevated levels of SEMA7A expression are notably linked to shorter overall survival and distant metastasis-free survival among patients with BC. The efficiency of SEMA7A as a reliable prognostic biomarker for BC has been substantiated by the validation of ROC curves and nomograms.Conclusion: SEMA7A has the potential to function as a prognostic indicator for BC, and its correlation with immune infiltration in BC is significant.Keywords: SEMA7A, breast cancer, biomarker, prognosis, methylation, immune infiltration, nomogram, bioinformatics

Attack detection and recovery are fundamental elements for the operation of safe and resilient cyber-physical systems. Most of the literature focuses on attack-detection, while leaving attack-recovery as an open problem. In this paper, we propose novel attack-recovery control for securing cyber-physical systems. Our recovery control consists of new concepts required for a safe response to attacks, which includes the removal of poisoned data, the estimation of the current state, a prediction of the reachable states, and the online design of a new controller to recover the system. The synthesis of such recovery controllers for cyber-physical systems has barely investigated so far. To fill this void, we present a formal method-based approach to online compute a recovery control sequence that steers a system under an ongoing sensor attack from the current state to a target state such that no unsafe state is reachable on the way. The method solves a reach-avoid problem on a Linear Time-Invariant (LTI) model with the consideration of an error bound ? = 0. The obtained recovery control is guaranteed to work on the original system if the behavioral difference between the LTI model and the system's plant dynamics is not larger than ?. Since a recovery control should be obtained and applied at the runtime of the system, in order to keep its computational time cost as low as possible, our approach firstly builds a linear programming restriction with the accordingly constrained safety and target specifications for the given reach-avoid problem, and then uses a linear programming solver to find a solution. To demonstrate the effectiveness of our method, we provide (a) the comparison to the previous work over 5 system models under 3 sensor attack scenarios: modification, delay, and reply; (b) a scalability analysis based on a scalable model to evaluate the performance of our method on large-scale systems.

Xiangyu Su,1,2 Guoqing Wang,3 Shiya Zheng,2 Chang Ge,4 Fei Kong,4 Cailian Wang1,2 1School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 2Department of Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 3Department of Pathology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 4Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of ChinaCorrespondence: Cailian Wang, Email wangcailian@seu.edu.cnBackground: Chemokines have been reported to play an important role in cancer immunotherapy. This study aimed to explore the chemokines involved in lung cancer immunotherapy.Methods: All the public data were downloaded from The Cancer Genome Atlas Program database. Quantitative real time-PCR was used to detect the mRNA level of specific molecules and Western blot was used for the protein level. Other experiments used include luciferase reporter experiments, flow cytometric analysis, Chromatin immunoprecipitation assay, ELISA and co-cultured system.Results: We found that the CCL7, CCL11, CCL14, CCL24, CCL25, CCL26, CCL28 had a higher level, while the CCL17, CCL23 had a lower level in immunotherapy non-responders. Also, we found that immunotherapy non-responders had a higher level of CD56dim NK cells, NK cells, Th1 cells, Th2 cells and Treg, yet a lower level of iDC and Th17 cells. Biological enrichment analysis indicated that in the patients with high Treg infiltration, the pathways of pancreas beta cells, KRAS signaling, coagulation, WNT BETA catenin signaling, bile acid metabolism, interferon alpha response, hedgehog signaling, PI3K/AKT/mTOR signaling, apical surface, myogenesis were significantly enriched in. CCL7, CCL11, CCL26 and CCL28 were selected for further analysis. Compared with the patients with high CCL7, CCL11, CCL26 and CCL28 expression, the patients with low CCL7, CCL11, CCL26 and CCL28 expression had a better performance of immunotherapy response and this effect might partly be due to Treg cells. Furthermore, biological exploration and clinical correlation of CCL7, CCL11, CCL26 and CCL28 were conducted, Finally, CCL28 was selected for validation. Experiments showed that under the hypoxia condition, HIF-1α was upregulated, which can directly bind to the promoter region of CCL28 and lead to its higher level. Also, CCL28 secreted by lung cancer cells could induce Tregs infiltration.Conclusion: Our study provides a novel insight focused on the chemokines in lung cancer immunotherapy. Also, CCL28 was identified as an underlying biomarker for lung cancer immunotherapy.Keywords: chemokines, lung adenocarcinoma, immunotherapy, Tregs, HIF-1&#x03B1

Yongchao Yu,1– 3,&ast; Jin Wang,1– 3,&ast; Dongying Liao,1– 3 Dou Zhang,1– 3 Xiaojiang Li,1,2 Yingjie Jia,1,2 Fanming Kong1– 3 1Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, People’s Republic of China; 3Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fanming Kong, Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China, Tel +862227986525, Email kongfanming08@163.comAbstract: Although targeted drugs improved the therapeutic effect of HER2-positive breast cancer, the long-term prognosis was still poor. In this regard, the research and development of antibody-drug conjugates (ADCs) came into being and made a lot of progress. ADCs had the characteristics of both chemotherapeutic agents and targeted agents by combining chemotherapeutic agents and targeted agents through a linker. It not only had a strong anti-tumor effect on HER2-positive breast cancer, but also had certain anti-tumor effects on HER2-low and even HER2-negative patients. In addition, the clinical researches of ADCs combined with immune checkpoint inhibitors (ICIs) therapy had also made a great breakthrough. This review aimed to summarize the clinical progress of ADCs, in particular the two drugs approved by the US Food and Drug Administration (FDA) for HER2-positive metastatic breast cancer as well as to summarize the current status of ADCs in combination with ICIs.Keywords: breast cancer, HER2-positive, antibody-drug conjugates, immunotherapy, advances

Kunpeng Wang,1 Xiongying Miao,2 Fanhua Kong,2 Siqi Huang,3 Jinggang Mo,1 Chong Jin,1 Yanwen Zheng2 1Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, 318000, Zhejiang, People’s Republic of China; 2Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China; 3Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of ChinaCorrespondence: Yanwen ZhengDepartment of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of ChinaEmail zyw.1018@csu.edu.cnBackground and Aim: Pancreatic cancer is one of the most malignant tumors worldwide. Zuojin pills (ZJP), a traditional Chinese medicine (TCM) formula, which can treat a variety of cancers. However, the active compounds present in ZJP and the potential mechanisms through which ZJP acts against pancreatic cancer have not been thoroughly investigated.Methods: Data on pancreatic cancer-related genes, bioactive compounds, and potential targets of ZJP were downloaded from public databases. Bioinformatics analysis, including protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, was conducted to identify important components, potential targets, and signaling pathways through which ZJP affects pancreatic cancer. The results of this analysis were verified by in vitro experiments.Results: The network pharmacology analysis results showed that 41 compounds and 130 putative target genes of ZJP were associated with anti-pancreatic cancer effects. ZJP may exert its inhibitory effects against pancreatic cancer by acting on key targets such as JUN, TP53, and MAPK1. Moreover, KEGG analysis indicated that the anti-pancreatic cancer effect of ZJP was mediated by multiple pathways, such as the PI3K-AKT, IL-17, TNF, HIF-1, and P53 signaling pathways. Among these, the PI3K-AKT signaling pathway, which included the highest number of enriched genes, may play a more important role in treating pancreatic cancer. The in vitro results showed that ZJP significantly inhibits the cell cycle and cell proliferation through the PI3K/AKT/caspase pathway and that it can induce apoptosis of pancreatic cancer cells, consistent with the results predicted by network pharmacological methods.Conclusion: This study preliminarily investigated the pharmacological effects of ZJP, which appear to be mediated by multiple compounds, targets and pathways, and its potential therapeutic effect on pancreatic cancer. Importantly, our work provides a promising approach for the identification of compounds in TCM and the characterization of therapeutic mechanisms.Keywords: pancreatic cancer, Zuojin pill, network pharmacology, traditional Chinese medicine, proliferation, apoptosis

Despite full immunoprophylaxis, mother-to-child transmission (MTCT) of Hepatitis B Virus still occurs in approximately 2-5% of HBsAg positive mothers. Little is known about the bottleneck of HBV transmission and the evolution of viral quasispecies in the context of MTCT. Here we adopted a newly developed tag linkage deep sequencing method and analyzed the quasispecies of four MTCT pairs that broke through immunoprophylaxis. By assigning unique tags to individual viral sequences, we accurately reconstructed HBV haplotypes in a region of 836 bp, which contains the major immune epitopes and drug resistance mutations. The detection limit of minor viral haplotypes reached 0.1% for individual patient sample. Dominance of "a determinant" polymorphisms were observed in two children, which pre-existed as minor quasispecies in maternal samples. In all four pairs of MTCT samples, we consistently observed a significant overlap of viral haplotypes shared between mother and child. We also demonstrate that the data can be potentially useful to estimate the bottleneck effect during HBV MTCT, which provides information to optimize treatment for reducing the frequency of MTCT.

Tianshu Jia,1 Rui Zhang,1 Fanfei Kong,2 Qianjiao Zhang,3 Zhuo Xi1 1Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 3Pain Department, The People’s Hospital of Liaoning Province, Shenyang, People’s Republic of ChinaCorrespondence: Zhuo XiDepartment of Neurosurgery, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Shenyang, People’s Republic of ChinaTel +86 189 4025 8425Email neurosurgeon-xz@hotmail.comPurpose: World Health Organization (WHO) Grades II and III gliomas [also known as low grade gliomas (LGGs)] displayed different malignant behaviors and survival outcomes compared to Grade IV gliomas. This study aimed to identify the prognostic predictive value of a novel cumulative prognostic score [combined with fibrinogen and albumin levels (FA score)], establish and validate a point-based nomogram in LGG patients.Patients and Methods: A total of 91 patients who underwent total glioma resection at Shengjing Hospital of China Medical University between 2011 and 2013 were enrolled to establish a prognostic nomogram. All patients were histologically diagnosed as grades II/III, and never received radiotherapy or chemotherapy before surgery. Data collection included patient characteristics, clinicopathological factors, and preoperative hematology results. The performance of the nomogram was subsequently validated by the concordance index (c-index), calibration curve, and receiver operating characteristic (ROC) curve.Results: The FA score was negatively associated with the overall survival (OS) of LGG patients (p < 0.001). The results of multivariate analysis showed that FA score [p = 0.006, HR = 1.92, 95% confidence interval (CI): 1.21– 3.05], age (p = 0.002, HR = 3.014, 95% CI:1.52– 5.97), and white blood count (p < 0.001, HR = 4.24, 95% CI: 2.08– 8.67) were independent prognostic factors for overall survival (OS). The study established a nomogram to predict OS with a c-index of 0.783 (95% CI, 0.72– 0.84).Conclusion: FA score might be a potential prognostic biomarker for LGG patients, and a reliable point-based nomogram will help clinicians to decide on the best treatment plans.Keywords: prognostics, fibrinogen, albumin, low-grade gliomas, nomogram

A Ni/C-MoS2 coating was electrospark deposited by using an electrode made of sinered Ni-C-MoS2 composite on a CrNi3MoVA steel substrate, and its nano-mechanical properties and tribological properties were obtained by utilizing nano-indenter and friction-abrasion testing machine. The results showed that the phase constitution of the as-deposited Ni/C-MoS2 coating mainly includes graphite, MoS2, γ-Ni, MoO2, NixS and MoC. Compared with the CrNi3MoVA steel and Ni/MoS2 coating, the Ni/C-MoS2 coating exhibits better tribological properties due to the matrix strengthened by MoO2 and MoC, and the synergistic lubrication effect of graphite and MoS2 in the Ni/C-MoS2 coating. [ABSTRACT FROM AUTHOR]

Huzi Li,1– 3 Zhendong Duan,2 Cheng Zhao,2 Wenyan Fang,2 Yingjie Jia,2 Xiaojiang Li,2 Fanming Kong,2 Lujun Zhao1 1Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, and Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 2Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 3Graduate School of Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Lujun ZhaoDepartment of Radiology, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin, People’s Republic of China, Email tjdoctorzhao@163.comBackground: A proportion of patients with synchronous oligometastatic non-small cell lung cancer (NSCLC) have poor survival, and currently no standard treatment is available, which poses a great challenge to physicians. This study aimed to assess and compare the efficacy and safety of the combination of brachytherapy with iodine-125 seeds and systemic chemotherapy versus systemic chemotherapy alone for synchronous extracranial oligometastatic NSCLC.Materials and Methods: After a systematic retrospective review of the case database between 1st Mar 2014 and 30th Mar 2018, data were obtained on 69 NSCLC patients with extracranial oligometastatic NSCLC. Among them, 32 patients received brachytherapy with iodine-125 seeds combined with systemic chemotherapy (group A), and the remaining 37 patients received chemotherapy alone (group B). The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and complications.Results: The demographic and clinical characteristics were not significantly different between the groups (all p> 0.05). The overall 3-month ORR was significantly higher in group A (65.6% vs 37.8%, p=0.030) than in group B. With a median follow-up time of 23 months, the PFS and OS were 11.6 (95% CI: 7.0– 16.2) months vs 6.3 (95% CI: 3.4– 9.2) months (p=0.036) and 17.6 (95% CI: 13.9– 21.3) months vs 11.2 (95% CI: 7.7– 14.7) months (p=0.042) in groups A and B, respectively. Furthermore, in Cox regression analysis, local brachytherapy was an independent prognostic factor for both PFS (HR=0.416, 95% CI: 0.246– 0.702, p=0.001) and OS (HR=0.375, 95% CI: 0.216– 0.653, p=0.001). Severe complications were not observed in either of the groups.Conclusion: The combination of brachytherapy with iodine-125 seeds and systemic chemotherapy is superior to chemotherapy alone for synchronous extracranial oligometastatic NSCLC.Keywords: brachytherapy, iodine-125 seeds, NSCLC, oligometastatic, chemotherapy

Yang Yan,1,* Yiping Wang,1,* Yuxia Liu,2 Tao Chen,3 Yaoli Zhu,4 Huiqing Li,5 Fangen Kong1 1Department of Neurosurgery, The Fifth Affiliated Hospital Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 2Department of Gastrointestinal Surgery, The Fifth Affiliated Hospital Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 3Department of Spine Surgery, The Fifth Affiliated Hospital Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 4Department of Critical Care Medicine, The Fifth Affiliated Hospital Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 5Department of Neurology, The Fifth Affiliated Hospital Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fangen Kong Email uyangleyanwlpty@163.comPurpose: Long non-coding RNAs (lncRNAs) have been reported to be involved in a variety of cancers, including glioma. However, the exact role and underlying mechanism of lncRNA AGAP2 antisense RNA 1 (AGAP2-AS1) in glioma have not yet been fully elucidated.Methods: The expression levels of AGAP2-AS1, microRNA-628-5p (miR-628-5p) and pleiotrophin (PTN) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration and invasion were detected by Cell Counting Kit-8 (CCK-8) assay, flow cytometry, transwell assay, respectively. Western blot assay was used to detect the protein level of PTN. The interaction between miR-628-5p and AGAP2-AS1 or PTN was predicted by bioinformatics software and confirmed by the dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Murine xenograft model was established to confirm the role of AGAP2-AS1 in glioma progression in vivo.Results: AGAP2-AS1 expression was upregulated in glioma tissues and cells. Knockdown of AGAP2-AS1 inhibited the proliferation, migration and invasion, but facilitated apoptosis in glioma cells. Moreover, AGAP2-AS1 could directly bind to miR-628-5p and its overexpression reversed the anti-tumor effect of miR-628-5p restoration on the progression of glioma cells. In addition, miR-628-5p directly targeted PTN and its inhibition abolished the inhibitory effect of PTN knockdown on the progression of glioma cells. Furthermore, AGAP2-AS1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-628-5p to modulate PTN expression. Besides, AGAP2-AS1 depletion reduced tumor growth by upregulating miR-628-5p and downregulating PTN.Conclusion: AGAP2-AS1 knockdown suppressed cell proliferation, migration and invasion but promoted cell apoptosis in glioma cells by regulating miR-628-5p/PTN axis, providing novel avenues for treatment of glioma.Keywords: glioma, AGAP2-AS1, miR-628-5p, PTN, cell progression

Siqi Huang,1 Zheyu Zhang,1 Wenqun Li,2 Fanhua Kong,3 Pengji Yi,1 Jianhua Huang,4 Dan Mao,1 Weijun Peng,1 Sifang Zhang1 1Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 2Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 3Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 4Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410013, People’s Republic of ChinaCorrespondence: Sifang Zhang; Weijun PengDepartment of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of ChinaTel +86-73185292111Email sifangzhang2005@csu.edu.cn; pengweijun87@csu.edu.cnBackground: Zuojinwan (ZJW), a famous Chinese medicine formula, has been widely used to treat colorectal cancer (CRC). However, its bioactive compounds, potential targets, and molecular mechanism remain largely elusive.Aim: A network pharmacology-based strategy combined with molecular docking studies and in vitro validation were employed to investigate bioactive compounds, potential targets, and molecular mechanism of ZJW against CRC.Materials and Methods: Bioactive compounds and potential targets of ZJW, as well as related genes of CRC, were acquired from public databases. Important ingredients, potential targets, and signaling pathways were determined through bioinformatics analysis, including protein–protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking and cell experiments were performed to further verify the findings.Results: A total of 36 bioactive ingredients of ZJW and 163 gene targets of ZJW were identified. The network analysis revealed that quercetin, baicalein, wogonin, beta-sitosterol, and isorhamnetin may be candidate agents. The AKT1, JUN, CDKN1A, BCL2L1, and NCOA1 could become potential drug targets. The KEGG indicated that PI3K-AKT signaling pathway may play an important role in the effect of ZJW against CRC. Molecular docking suggested that quercetin, baicalein, and wogonin combined well with AKT1 and JUN. The in vitro experiment showed that quercetin, the most important ingredient of ZJW, could induce apoptosis of HCT116 cells through PI3K-Akt signaling pathway. This finding was congruent with the prediction obtained through the network pharmacology approach.Conclusion: This study comprehensively illuminated the active ingredients, potential targets, and molecular mechanism of ZJW against CRC. It also provided a promising approach to uncover the scientific basis and therapeutic mechanism of traditional Chinese medicine (TCM) formula treating for disease.Keywords: Zuojinwan, colorectal cancer, network pharmacology, PI3K/AKT signal pathway