A molecular approach to triple-negative breast cancer: targeting the Notch signaling pathway

ABSTRACT Introduction Triple-negative breast cancer is an aggressive subtype of breast cancer characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. This phenotype renders triple-negative breast cancer cells refractory to conventional therapies, resulting in poor clinical outcomes and an urgent need for novel therapeutic approaches. Recent studies have implicated dysregulation of the Notch receptor signaling pathway in the development and progression of triple-negative breast cancer. Objective This study aimed to conduct a comprehensive literature review to identify potential therapeutic targets of the Notch pathway. Our analysis focused on the upstream and downstream components of this pathway to identify potential therapeutic targets. Results Modulating the Notch signaling pathway may represent a promising therapeutic strategy to treat triple-negative breast cancer. Several potential therapeutic targets within this pathway are in the early stages of development, including upstream (such as Notch ligands) and downstream (including specific molecules involved in triple-negative breast cancer growth). These targets represent potential avenues for therapeutic intervention in triple-negative breast cancer. Comments Additional research specifically addressing issues related to toxicity and improving drug delivery methods is critical for the successful translation of these potential therapeutic targets into effective treatments for patients with triple-negative breast cancer.

Progress of BRAF Gene Alteration in Non-small Cell Lung Cancer / 中国肺癌杂志

V-Raf murine sarcoma viral oncogene homolog B (BRAF) alteration is one of the most essential driver genes of non-small cell lung cancer (NSCLC). BRAF encodes serine/threonine protein kinases, and its mutations typically lead to protein compositional activation, thereby activating the mitogen-activated protein kinase kinase (MEK) signaling pathway. A promising new approach for the treatment of mutated BRAF and/or downstream MEK may provide customized treatment opportunities for BRAF driven NSCLC patients. However, combination therapy is necessary to overcome the difficulties such as short duration of benefit, poor therapeutic effect of non-V600 BRAF mutations and susceptibility to drug resistance. This article reviewed the progress in structural characteristics, related signaling pathways, mutation types of BRAF gene, and the clinical pathological relationship between BRAF mutations and NSCLC, as well as the therapy, in order to provide more evidences for clinical doctors to make treatment decisions.
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Research Progress of Granulocytic Myeloid-derived Suppressor Cells in Non-small Cell Lung Cancer / 中国肺癌杂志

Granulocytic myeloid-derived suppressor cells (G-MDSCs) are one of the main subgroups of MDSCs, which are widely enriched in most cancers. It can inhibit the killing function of T-lymphocyte through the expression of arginase-1 (Arg-1) and reactive oxygen species (ROS), reshape the tumor immune microenvironment, and promote the occurrence and development of tumors. In recent years, more and more studies have found that G-MDSCs are significantly correlated with the prognosis and immunotherapy efficacy of patients with non-small cell lung cancer, and the use of drugs specifically targeting the recruitment, differentiation and function of G-MDSCs can effectively inhibit tumor progression. This article reviews the immunosuppressive effect of G-MDSCs in non-small cell lung cancer and the progress of related pathway targeting drugs.
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Drug-free targeted thrombolytic strategy based on gold nanoparticles-loaded human serum albumin fusion protein delivery system / 药学学报

Thrombus is a major factor leading to cardiovascular diseases such as myocardial infarction and stroke. Although fibrinolytic anti-thrombotic drugs have been widely used in clinical practice, they are still limited by narrow therapeutic windows, short half-lives, susceptibility to inactivation, and abnormal bleeding caused by non-targeting. Therefore, it is crucial to effectively deliver thrombolytic agents to the site of thrombus with minimal adverse effects. Based on the long blood circulation and excellent drug-loading properties of human serum albumin (HSA), we employed genetic engineering techniques to insert a functional peptide (P-selectin binding peptide, PBP) which can target the thrombus site to the N-terminus of HSA. The fusion protein was expressed using Pichia pastoris and purified by Ni-chelating affinity chromatography. After being loaded with gold nanoparticles (Au NPs), the fusion protein formed homogeneous and stable nanoparticles (named as PBP-HSA@Au) with a diameter of 17.7 ± 1.0 nm and a zeta potential of -11.3 ± 0.2 mV. Cytotoxicity and hemolysis tests demonstrated the superb biocompatibility of PBP-HSA@Au. Platelet-targeting experiments confirmed the thrombus-targeting ability conferred by the introduction of PBP into PBP-HSA@Au. Upon near-infrared ray (NIR) irradiation, PBP-HSA@Au rapidly converted light energy into heat, thereby disrupting fibrinogen and exhibiting outstanding thrombolytic efficacy. The designed HSA fusion protein delivery system provides a precise, rapid, and drug-free treatment strategy for thrombus therapy. This system is characterized by its simple design, high biocompatibility, and strong clinical applicability. All animal experiments involved in this study were carried out under the protocols approved by the Animal Experiment Ethics Committee of Jiangnan University [JN. No20230915S0301015(423)].

The role of glucose metabolism reprogramming and its targeted therapeutic agents in inflammation-related diseases / 药学学报

Cells undergo glucose metabolism reprogramming under the influence of the inflammatory microenvironment, changing their primary mode of energy supply from oxidative phosphorylation to aerobic glycolysis. This process is involved in all stages of inflammation-related diseases development. Glucose metabolism reprogramming not only changes the metabolic pattern of individual cells, but also disrupts the metabolic homeostasis of the body microenvironment, which further promotes aerobic glycolysis and provides favourable conditions for the malignant progression of inflammation-related diseases. The metabolic enzymes, transporter proteins, and metabolites of aerobic glycolysis are all key signalling molecules, and drugs can inhibit aerobic glycolysis by targeting these specific key molecules to exert therapeutic effects. This paper reviews the impact of glucose metabolism reprogramming on the development of inflammation-related diseases such as inflammation-related tumours, rheumatoid arthritis and Alzheimer's disease, and the therapeutic effects of drugs targeting glucose metabolism reprogramming on these diseases.

Research progress in micro/nanobubbles for ultrasound diagnosis or treatment / 药学学报

In the past few decades, microbubbles were widely used as ultrasound contrast agents in the field of tumor imaging. With the development of research, ultrasound targeted microbubble destruction technology combined with drug-loaded microbubbles can achieve precise drug release and play a therapeutic role. As a micron-scale carrier, microbubbles are difficult to penetrate the endothelial cell space of tumors, and nano-scale drug delivery system—nanobubbles came into being. The structure of the two is similar, but the difference in size highlights the unique advantages of nanobubbles in drug delivery. Based on the classification principle of shell materials, this review summarized micro/nanobubbles used for ultrasound diagnosis or treatment and discussed the possible development directions, providing references for the subsequent development.

Research progress of biological agents in thyroid-associated ophthalmopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Thyroid-associated ophthalmopathy(TAO)is a rare organ-specific autoimmune disease with an unclear pathogenesis. At present, the treatment still relies mainly on glucocorticoids and traditional immunosuppressants. However, some patients respond poorly to these drugs and experience treatment-related adverse reactions, highlighting the urgent need for novel drugs for TAO treatment. In recent years, with the deepening of research on the pathogenesis of TAO, a multitude of biologics targeting specific targets have emerged. Among them, teprotumumab, which targets the insulin-like growth factor-I receptor(IGF-IR), has been approved by the Food and Drug Administration for the treatment of TAO, and several other biologics are currently in clinical trials. This review provides the latest reference for the clinical prevention, treatment, and research of TAO by summarizing the current clinical research status of biologics targeting IGF-IR, neonatal Fc receptor(FcRn), thyroid-stimulating hormone receptor(TSHR), B cells, cytokines, and other biological agents in TAO and analyzing their impact on clinical treatment and future research trends.

Effects of hypoxia-inducible factors on tumor mesenchymal cells: a review / 预防医学

@#Hypoxia is the most common tumor microenvironment caused by rapid proliferation of tumor cells, and hypoxia-inducible factor (HIF) is the main transcription factor for tumor cells to adapt to hypoxia. Current research has found that HIF can interact with a variety of mesenchymal cells such as fibroblasts, endothelial cells and immune cells in the tumor microenvironment, leading to the transcription and expression of target genes in response to hypoxia, which ultimately promotes tumor angiogenesis, and induces physiological changes such as migration, invasion, and immune escape of tumor cells. However, the signaling pathways involved in the HIF regulatory mechanism are complex, and the mechanism of HIF in the tumor microenvironment need to be further investigated, also most HIF inhibitors are still in the preclinical research stage. This paper reviews the research progress on the effects of HIF on tumor mesenchymal stromal cells to provide a theoretical basis for the diagnosis, prevention and treatment of tumors targeting HIF.

Analysis of Differences in Secondary Metabolites from Dendrobium nobile Stems Cultivated on Epiphytic Rocks in Different Growth Years Based on Metabolomics / 中国实验方剂学杂志

ObjectiveTo study the changing characteristics of secondary metabolic compounds accumulated in Dendrobium nobile stems at different growth years， a simulated wild stone plant， in order to provide a theoretical basis for rational planning of the harvesting period of D. nobile. MethodUltra-high performance liquid chromatography-mass spectrometry（UPLC-MS/MS） was used to detect and analyze the secondary metabolites in the stems of 1-year-old， 2-year-old， and 3-year-old D. nobile. The mass spectrometry data were processed using Analyst 1.6.3 software， and all samples were subjected to principal component analysis（PCA）， cluster heat map analysis， partial least squares-discriminant analysis（PLS-DA）， and differential secondary metabolites were screened based on variable importance in projection（VIP） values>1， fold change（FC）≥2 and FC≤0.5. Then differential secondary metabolites were identified based on relative molecular weight， fragmentation ions and mass spectrometry database， and enriched pathways were identified based on the Kyoto Encyclopedia of Genes and Genomes（KEGG） database. ResultA total of 1 317 secondary metabolites were identified in the stems of D. nobile at three growth stages， with flavonoids， phenolic acids， alkaloids and terpenoids accounting for 76.55% of the total. Compared with the 1-year-old stems of D. nobile， 289 differential secondary metabolites were identified in the 2-year-old stems， of which 255 were up-regulated and 34 were down-regulated， 682 differential secondary metabolites were identified in the 3-year-old stems， of which 502 were up-regulated and 180 were down-regulated. Compared to the 2-year-old stems， the 3-year-old stems had 602 differential secondary metabolites， with 405 up-regulated and 197 down-regulated. As the growth stage of D. nobile increased， the top 10 up-regulated differential metabolites mainly included flavonoids， phenolic acids， phenylpropanoids and terpenoids， such as kaempferol derivatives， asperulosidic acid， apigenin derivatives， chrysoeriol derivatives， isorhamnetin derivatives， taxifolin derivatives， quercetin derivatives. KEGG enrichment analysis showed significant enrichment of secondary metabolites in the flavonoid biosynthesis， flavone， and flavonol biosynthesis， secondary metabolite biosynthesis， and phenylpropanoid biosynthesis pathways with the increase of growth years. ConclusionWith the increase of the growth years， the levels of secondary metabolites such as flavonoids， phenolic acids， phenylpropanoids and terpenoids in the wild-grown D. nobile have been significantly enhanced. In practical production， grading based on different growth years can be carried out to improve the medicinal and economic values of D. nobile.

Research progress of biomarkers for non-small cell lung cancer / 中国胸心血管外科临床杂志

@#Lung cancer is the leading cause of cancer-related deaths worldwide. Despite growing efforts for its early detection by screening populations at risk, the majority of lung cancer patients are still diagnosed in an advanced stage. In the last decade, the treatment of non-small cell lung cancer (NSCLC) has been improved significantly. Emerging options of targeted therapies and immunotherapies have shifted the management of lung cancer to a more personalized treatment approach, significantly influencing the clinical course and outcome of the disease. At present, molecular biomarkers are becoming a powerful tool for diagnosing cancer, predicting treatment response outcomes, and assessing prognosis. In this review, we summarized the biomarkers relevant to the diagnosis, prediction, and prognosis of NSCLC as well as promising novel predictive biomarkers in the future.

Targeted biotherapy for chronic obstructive pulmonary disease / 中国临床药理学与治疗学

Chronic obstructive pulmonary disease (COPD) is the most common chronic airway disease. The current status of treatment based mainly on bronchodilators and ICS is not sufficient for all of COPD patients. Various studies have attempted to use biologics targeting specific cytokines and their receptors in COPD patients to alleviate respiratory symptoms or reduce the risk of acute exacerbations. However, they failed to bring significant clinical benefits. More studies are needed to further determine the efficacy of targeted biotherapy for COPD.

Research progress and potential medical applications of anaplastic lymphoma kinase in treatment of non-small cell lung cancer / 中国药理学通报

During the treatment of non-small cell lung cancer ( NSCLC) , many patients have developed drug resistance due to the use of targeted EGFR inhibitors. The main reasons for drug resistance are EGFR site mutations and bypass activation. Activation of ALK pathway is one of the major types of bypass activation. A recent authoritative study indicates that ALK is closely related to immunotherapy. This article reviews the treatment of ALK in tumors from three aspects: the structure and physiological function of ALK, the small molecule inhibitor of ALK, the biological function of ALK and its related treatment methods for NSCLC, and prospects future directions for better application of ALK in the treatment of NSCLC.

Role of complement protein regulatory targets in diabetic retinopathy and its clinical research progress / 国际眼科杂志(Guoji Yanke Zazhi)

The complement system is a protein response system with a precise regulatory mechanism, which has the functions of mediating inflammation, regulating immune response, dissolving cells and clearing immune complexes. Diabetic retinopathy(DR)is a common and severe ocular complication of diabetes and one of the common irreversible blinding eye diseases in ophthalmology, and its pathogenesis is complex, including hypoxia, oxidative stress, inflammation and abnormal polyol metabolism pathway. In recent years, there has been more and more evidence that dysregulation and inflammation of immune system are important factors in the pathogenesis of DR, and a variety of complement proteins play an important role in key processes such as inflammation regulation and angiogenesis. Therefore, the central purpose of this review is to discuss the role of the complement system and related regulatory proteins in DR, with the aim of elucidating the close relationship between the complement proteins and the occurrence and development of DR, and providing important references and new ideas for the prevention and treatment of DR. At the same time, the clinical research of complement system-targeted drugs is further elaborated.

Research progress of chemotherapy-related diarrhea induced by molecularly targeted anti-tumor drugs / 中国药房

Diarrhea caused by chemotherapy is called chemotherapy-related diarrhea （CRD）. CRD can lead to reduced treatment effectiveness and compliance， affect the long-term outcome of tumor patients， and can be life-threatening in severe cases. In addition to conventional chemotherapy drugs， many molecularly targeted drugs are also associated with CRD， including small molecule epidermal growth factor receptor （EGFR） inhibitors， anti-EGFR monoclonal antibodies， phosphoinositide 3-kinase inhibitors， small molecule inhibitors of vascular endothelial growth factor receptor， BCR-ABL1 and KIT inhibitors， human epidermal growth factor receptor 2 target inhibitors， cyclin-dependent protein kinase inhibitors， antibody-drug conjugates and other molecularly targeted drugs. The occurrence mechanism may be related to the intestinal mucosal injury or enteritis caused by molecularly targeted drugs. The clinical manifestations are increased stool frequency and/or loose imposition， and patients are often associated with excess hyperproduction and/or colic. The incidence of CRD varies with different drugs. Great importance should be attached to collecting medical history and differential diagnosis， actively intervening and conducting dynamic evaluation， strengthening patient education， and timely detecting and preventing the occurrence of intestinal toxicity.

Immunostimulatory gene therapy combined with checkpoint blockade reshapes tumor microenvironment and enhances ovarian cancer immunotherapy

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

Advances in molecular-targeted therapy for unresectable pancreatic cancer / 临床肝胆病杂志

Pancreatic cancer is one of the most prevalent malignant tumors of the digestive system， and its incidence and mortality rates are increasing year by year. Most patients with pancreatic cancer are unable to receive surgery due to the advanced stage. Although chemotherapy regimens based on gemcitabine and fluorouracil have prolonged the survival time of patients to some extent， some patients cannot tolerate chemotherapy and hence lose the opportunity for treatment. With the advent of the era of precision medicine， molecular-targeted therapy has exhibited an excellent therapeutic efficacy and has thus become one of the most important treatment techniques for tumors； however， due to the high heterogeneity of pancreatic cancer and its complicated tumor microenvironment， molecular-targeted therapy for pancreatic cancer has not achieved notable results. Therefore， it is imperative to seek new therapeutic targets and medications to overcome this issue. This article reviews the latest advances in the research on molecular-targeted therapy for unresectable pancreatic cancer based on common molecular targets and tumor immunity-related therapeutic targets， in order to provide new treatment strategies for patients with pancreatic cancer.

Fanconi Anemia: Exploration of DNA Repair Pathways from Genetic Diseases to Cancer and Prospects for Treatment / 肿瘤防治研究

Fanconi anemia (FA) is an inheritable disorder that presents with bone marrow failure, developmental anomalies, and an increased susceptibility to cancer. The etiology of this condition stems from a genetic mutation that disrupts the proper repair of interstrand DNA cross-links (ICLs). The resultant dysregulation of the DNA damage response mechanism can induce genomic instability, thereby elevating the mutation rates and the likelihood of developing cancer. The FA pathway assumes a pivotal role in safeguarding genome stability through its involvement in the repair of DNA cross-links and the maintenance of overall genomic integrity. A mutation in the germ line of any of the genes responsible for encoding the FA protein results in the development of FA. The prevalence of aberrant FA gene expression in somatic cancer, coupled with the identification of a connection between FA pathway activation and resistance to chemotherapy, has solidified the correlation between the FA pathway and cancer. Consequently, targeted therapies that exploit FA pathway gene abnormalities are being progressively developed and implemented. This review critically examines the involvement of the FA protein in the repair of ICLs, the regulation of the FA signaling network, and its implications in cancer pathogenesis and prognosis. Additionally, it explores the potential utility of small-molecule inhibitors that target the FA pathway.

Application of Magnetic Resonance Imaging and Transrectal Ultrasound Image Fusion Targeted Transperineal Biopsy Technique Using Electromagnetic Needle Tracking Under Local Anaesthesia / 肿瘤防治研究

Objective To explore the effect and safety of magnetic resonance imaging and transrectal ultrasound (mpMRI-TRUS) image fusion targeted transperineal biopsy technique using electromagnetic needle tracking under local anesthesia. Methods We retrospectively analyzed the clinical and pathological data of 81 patients with mpMRI-TRUS image fusion targeted transperineal prostate biopsy using electromagnetic needle tracking under local anesthesia. Visual analog scale (VAS) and visual numeric scale (VNS) were used to evaluate the pain level and satisfaction of patients during prostate biopsy (VAS-1 and VNS-1), one hour after puncture (VAS-2 and VNS-2), and one day after surgery (VAS-3 and VNS-3). The perioperative clinical data and tumor positive rate of postoperative biopsy were recorded. Results The average prostate volume of 81 patients was 53.39±29.46 cm3. The PSA values of patients with PI-RADS scores of 2, 3, 4, and 5 were 9.14±2.31, 9.95±4.10, 14.77±6.36, and 32.17±24.39 ng/ml, respectively. The scores of VAS-1, VAS-2, and VAS-3 were 1.70±0.73, 1.16±0.58, and 0.53±0.55, respectively; the scores of VNS-1, VNS-2, and VNS-3 were 2.74±0.44, 3.69±0.46, and 3.84±0.37, respectively. The average surgical time was 17.47±3.44 minutes. Postoperative pathological results showed that the tumor positive rate of targeted prostate biopsy was 64.20%. According to the PI-RADS score for subgroup analysis, the tumor positive rates of patients with PI-RADS scores of 2, 3, 4, and 5 were 21.43%, 44.44%, 61.11%, and 96.77%, respectively. After transperineal prostate biopsy, gross hematuria occurred in 19.75% patients, and urinary retention occurred in 3.70%. The latter were relieved after symptomatic treatment. All patients did not experience complications, such as perineal puncture area hematoma, urinary tract infection, hematospermia, hematoma in perineal puncture area, urinary tract infection, hematospermia, vagus nerve reaction, or septic shock. Conclusion For suspected prostate cancer patients, mpMRI-TRUS image fusion targeted transperineal biopsy technique using electromagnetic needle tracking under local anesthesia is a feasible and easily tolerated surgical procedure. It has good safety and high tumor positive-detection rate, indicating that this technique is worthy of further clinical promotion and application.

Advances in Salmonella-mediated targeted tumor therapy / 药学学报

italic>Salmonella has emerged as a promising tumor-targeting strategy in recent years due to its good tumor targeting ability and certain safety. In order to further optimize its therapeutic effect, scientists have tried to modify Salmonella, including its attenuation and drug loading. This paper summarizes the mechanism and research progress of Salmonella-mediated targeted tumor therapy, and introduces the strategies and related progress of its modification and optimization. At the same time, the advantages, current challenges and future development directions of Salmonella-mediated tumor therapy are summarized.

The Development of Chinese Herbal Formulae for Non-severe COVID-19 Based on Artificial Intelligence Technology and Investigation of Its Action Mechanisms / 中医杂志

ObjectiveTo develop traditional Chinese medicine （TCM） formulae for the treatment of nonsevere coronavirus disease 2019 （COVID-19） and to explore its anti-inflammatory mechanism. MethodsThe dysregulated signaling pathways were determined in macrophages from bronchoalveolar lavage fluid of COVID-19 patients and in lung epithelial cells infected with SARS-CoV-2 in vitro based on transcriptome analysis. A total of 102 TCM formulae for the clinical treatment of nonsevere COVID-19 were collected through literature. The pathway-reversing rates of these formulae in macrophages and lung epithelial cells were evaluated based on signature signaling pathways， and the basic formula was determined in conjunction with TCM theory. The commonly used Chinese materia medica for nonsevere COVID-19 were summarized from the 102 TCM formulae as abovementioned. And together with the screening results from the Pharmacopoeia of the People's Republic of China， a “Chinese materia medica pool” was esta-blished for the development of TCM formulae for COVID-19. The regulatory effects of each herb on signaling pathways were obtained based on targeted transcriptome analysis. Oriented at reversing dysregulated signaling pathways of COVID-19， the calculation was carried out， and the artificial intelligent methods for compositing formulae， that are exhaustive method and parallel computing， were used to obtain candidate compound formulas. Finally， with reference to professional experience， an innovative formula for the treatment of nonsevere COVID-19 was developed. The ethanol extract of the formula was evaluated for its anti-inflammatory effects by detecting the mRNA expression of interleukin 1b （Il1b）， C-X-C motif chemokine ligand 2 （Cxcl2）， C-X-C motif chemokine ligand 10 （Cxcl10）， C-C motif chemokine ligand 2 （Ccl2）， nitric oxide synthase 2 （Nos2）， and prostaglandin-endoperoxide synthase 2 （Ptgs2） using reverse transcription-quantitative polymerase chain reaction （RT-qPCR） in RAW264.7 cells treated with lipopolysaccharide （LPS）. ResultsIn macrophages and lung epithelial cells， 34 dysregulated signaling pathways associated with COVID-19 were identified respectively. The effects of the 102 formulae for clinical treatment of nonsevere COVID-19 were evaluated based on the dysregulated signaling pathways and targeted transcriptome， and the result showed that Yinqiao Powder and Pingwei Powder （银翘散合平胃散， YQPWP） ranked first， reversing 91.18% of the dysregulated signaling pathways in macrophages and 100% of the dysregulated signaling pathways in lung epithelial cells. Additionally， YQPWP had the function of scattering wind and clearing heat， resolving toxins and removing dampness in accordance with the pathogenesis of wind-heat with dampness in COVID-19. It was selected as the basic formula， and was further modified and optimized to develop an innovative fomula Qiaobang Zhupi Yin （翘蒡术皮饮， QBZPY） based on expert experience and artificial intelligence in composing formulae. QBZPY can reverse all the dysregulated signaling pathways associated with COVID-19 in macrophages and lung epithelial cells， with the reversing rates of 100%. The chief medicinal of QBZPY， including Lianqiao （Fructus Forsythiae）， Xixiancao （Herba Siegesbeckiae） and Niubangzi （Fructus Arctii）， can down-regulate multiple signaling pathways related with virus infection， immune response， and epithelial damage. RT-qPCR results indicated that compared with the model group， the QBZPY group down-regulated the mRNA expression of Il1b， tumor necrosis factor （Tnf）， Cxcl2， Cxcl10， Ccl2， Nos2 and Ptgs2 induced by LPS in RAW264.7 cells （P＜0.05 or P＜0.01）. ConclusionBased on targeted transcriptome analysis， expert experience in TCM and artificial intelligence， QBZPY has been developed for the treatment of nonsevere COVID-19. The ethanol extract of QBZPY has been found to inhibit mRNA expression of several pro-inflammatory genes in a cellular inflammation model.