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Xu Tian,1,* Fangrong Liu,2,* Feili Li,3 Yi Ren,4 Hongcai Shang5 1Chongqing Center for Evidence-Based Traditional Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400020, People’s Republic of China; 2Outpatient Department, Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China; 3Department of Nursing, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400020, People’s Republic of China; 4Department of Classic Traditional Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400020, People’s Republic of China; 5Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 101121, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi Ren, Department of Classic Traditional Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, No. 6 of 7th Branch of Panxi Road, Jiangbei District, Chongqing, People’s Republic of China, Tel/Fax +86 023 67776180, Email cqszyyrenyi@163.com Hongcai Shang, Dongzhimen Hospital, Beijing University of Chinese Medicine, No. 5 of Haiyuncang, Dongcheng District, Beijing, People’s Republic of China, Tel/Fax +86 010 84013276, Email yxtx880919@163.comPurpose: While the benefits of exercises for chronic obstructive pulmonary disease (COPD) are well-established, the relative effectiveness of different exercise types for stable COPD remains unclear. This network meta-analysis aims to investigate the comparative effects of aerobic exercise (AE), resistance training (RT), endurance training (ET), and high-intensity interval training (HIIT) in stable COPD.Methods: Electronic searches were performed in PubMed, Embase, and the Cochrane library to identify relevant randomized controlled trials (RCTs) investigating the effects of exercises on 6-minute walk test distance (6MWD), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC), and St. George’s Respiratory Questionnaire (SGRQ) score. Two authors screened the retrieved articles, extracted relevant data, and assessed the risk of bias. Network meta-analysis was conducted using Stata 14.0.Results: This study included a total of 19 studies involving 951 patients with stable COPD. HIIT emerged as the most favorable exercise type for enhancing 6MWD, with a probability of 82.9%. RT exhibited the greatest efficacy in reducing SGRQ scores, with probability of 49.8%. Notably, ET demonstrated superiority in improving FEV1 and FVC, with probabilities of being most effective at 78.1% and 42.0%, respectively.Conclusion: This study suggests that HIIT may be a viable intervention for improving exercise capacity in stable COPD patients, compared to AE, RR, and ET. RT may hold promise for improving quality of life, and ET may demonstrate superiority in improving pulmonary function. However, variation in response likely depends on patient characteristics, program parameters, and delivery context. Future research should explore the synergistic effects of combining RT with ET/HIIT, focusing on patient subgroups, optimal dosing, and settings, as current guidelines indicate this combination may offer the most significant benefits.Keywords: COPD, exercise, pulmonary function, quality of life, network meta-analysis

Kehua Jiang,1 Qing Wang,1 Xiao-Long Chen,1 Xiaodong Wang,1 Xiaoya Gu,1 Shuangshuang Feng,1 Jian Wu,2 Haojie Shang,2 Xiaozhuo Ba,2 Yanlong Zhang,1 Kun Tang2 1Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China; 2Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaCorrespondence: Yanlong Zhang, Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China, Email ylzhang3030@163.com Kun Tang, Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Qiaokou District, Wuhan, 430030, People’s Republic of China, Email tangsk1990@163.comAbstract: Tryptophan (Trp) metabolism plays a vital role in cancer immunity. Indoleamine 2.3-dioxygenase 1 (IDO1), is a crucial enzyme in the metabolic pathway by which Trp is degraded to kynurenine (Kyn). IDO1-mediated Trp metabolites can inhibit tumor immunity and facilitate immune evasion by cancer cells; thus, targeting IDO1 is a potential tumor immunotherapy strategy. Recently, numerous IDO1 inhibitors have been introduced into clinical trials as immunotherapeutic agents for cancer treatment. However, drawbacks such as low oral bioavailability, slow onset of action, and high toxicity are associated with these drugs. With the continuous development of nanotechnology, medicine is gradually entering an era of precision healthcare. Nanodrugs carried by inorganic, lipid, and polymer nanoparticles (NPs) have shown great potential for tumor therapy, providing new ways to overcome tumor diversity and improve therapeutic efficacy. Compared to traditional drugs, nanomedicines offer numerous significant advantages, including a prolonged half-life, low toxicity, targeted delivery, and responsive release. Moreover, based on the physicochemical properties of these nanomaterials (eg, photothermal, ultrasonic response, and chemocatalytic properties), various combination therapeutic strategies have been developed to synergize the effects of IDO1 inhibitors and enhance their anticancer efficacy. This review is an overview of the mechanism by which the Trp-IDO1-Kyn pathway acts in tumor immune escape. The classification of IDO1 inhibitors, their clinical applications, and barriers for translational development are discussed, the use of IDO1 inhibitor-based nanodrug delivery systems as combination therapy strategies is summarized, and the issues faced in their clinical application are elucidated. We expect that this review will provide guidance for the development of IDO1 inhibitor-based nanoparticle nanomedicines that can overcome the limitations of current treatments, improve the efficacy of cancer immunotherapy, and lead to new breakthroughs in the field of cancer immunotherapy.Keywords: indoleamine 2, 3-dioxygenase 1, IDO1, IDO1 inhibitors, nanodrugs, nanodelivery, cancer immunotherapy, combination therapy

Qiu Huang,* Yue Ge,* Yu He, Jian Wu, Yonghua Tong, Haojie Shang, Xiao Liu, Xiaozhuo Ba, Ding Xia, Ejun Peng, Zhiqiang Chen, Kun Tang Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiqiang Chen; Kun Tang, Email zhqchen8366@163.com; tangsk1990@163.comAbstract: Cancer-associated fibroblasts (CAF) are the most abundant stromal cells in the tumor microenvironment (TME), especially in solid tumors. It has been confirmed that it can not only interact with tumor cells to promote cancer progression and metastasis, but also affect the infiltration and function of immune cells to induce chemotherapy and immunotherapy resistance. So, targeting CAF has been considered an important method in cancer treatment. The rapid development of nanotechnology provides a good perspective to improve the efficiency of targeting CAF. At present, more and more researches have focused on the application of nanoparticles (NPs) in targeting CAF. These studies explored the effects of different types of NPs on CAF and the multifunctional nanomedicines that can eliminate CAF are able to enhance the EPR effect which facilitate the anti-tumor effect of themselves. There also exist amounts of studies focusing on using NPs to inhibit the activation and function of CAF to improve the therapeutic efficacy. The application of NPs targeting CAF needs to be based on an understanding of CAF biology. Therefore, in this review, we first summarized the latest progress of CAF biology, then discussed the types of CAF-targeting NPs and the main strategies in the current. The aim is to elucidate the application of NPs in targeting CAF and provide new insights for engineering nanomedicine to enhance immune response in cancer treatment.Keywords: nanoparticles, cancer therapy, cancer-associated fibroblasts, drug delivery, cancer, nanomedicine

Haotian Shang, Yanan Chen, Qiulu Wang, Yongliang Yang, Jingyu Zhang Department of Oncology, Clinical College of Second People’s Hospital of Lianyungang, Bengbu Medical College, Lianyungang, People’s Republic of ChinaCorrespondence: Jingyu Zhang, Department of Oncology, Clinical College of Second People’s Hospital of Lianyungang, Bengbu Medical College, No. 41, Hailian East Road, Haizhou District, Lianyungang City, Jiangsu Province, People’s Republic of China, Email zhangjingyu@njmu.edu.cnPurpose: This study aimed to investigate the relationship between peripheral blood indices and the efficacy and prognosis of advanced esophageal squamous cell carcinoma (ESCC) patients treated with camrelizumab.Patients and Methods: We retrospectively analyzed 64 patients who received camrelizumab for advanced ESCC at the Second People’s Hospital of Lianyungang City between July 2020 and June 2022. The study included examination of the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the systemic inflammation index (SII), the lymph-to-monocytes ratio (LMR), the absolute lymphocyte count (ALC), and lactate dehydrogenase (LDH). We used multivariate logistic regression analysis to explore the link existing between peripheral blood and the efficacy of treatment. Determination of potential prognostic factors for Progression-free survival (PFS) and Overall survival (OS) using Cox regression analysis. The nomogram model was developed based on the results of the Cox multivariate analysis. Patients were divided into three groups according to the reduction in LDH and LDL levels before treatment, and the Kaplan-Meier survival curves for the three groups were compared and ROC curves for LDH combined with PLR were plotted.Results: Lower LDH (OR=6.237, 95% CI: 1.625– 23.944) were independently associated with disease control rates(DCR). LDH was independently correlated with PFS (HR: 0.227 95% CI: 0.099– 0.517). LDH and PLR were independently linked to OS. The C index of the nomogram model is 0.819, indicating good predictive performance. Kaplan-Meier Survival Curve suggested better OS in patients with reduced pretreatment LDH and PLR. The area under the ROC curve showed that the LDH index combined with the PLR index predicts patient survival better than the index alone.Conclusion: LDH combined with PLR predicted prognosis in patients with ESCC treated with camrelizumab.Keywords: esophageal squamous cell carcinoma, camrelizumab, immunotherapy, peripheral blood, prognostic index

Xiang Li,1,* Lei Hu,1,* Abid Naeem,2,3,* Shanghua Xiao,2 Ming Yang,2 Hongming Shang,4 Jing Zhang1,2 1National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, 330004, People’s Republic of China; 3School of Life Science, Advanced Research Institute of Multidisciplinary Science, School of Medical Technology, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, People’s Republic of China; 4Department of Biochemistry & Chemical Biology, Vanderbilt University, Nashville, TN, USA*These authors contributed equally to this workCorrespondence: Jing Zhang, Tel/Fax +86 79187118658, Email jing.zhang@jxutcm.edu.cnAbstract: Neutrophil extracellular traps (NETs) are extracellular fibers composed of deoxyribonucleic acid (DNA) and decorated proteins produced by neutrophils. Recently, NETs have been associated with the development of many diseases, including tumors. Herein, we reviewed the correlation between NETs and tumors. In addition, we detailed active compounds from traditional herbal medicine formulations that inhibit NETs, related nanodrug delivery systems, and antibodies that serve as “guiding moieties” to ensure targeted delivery to NETs. Furthermore, we discussed the strategies used by pathogenic microorganisms to evade NETs.Keywords: neutrophil extracellular traps, cancer, traditional herbal medicine formulations, nano delivery systems

Huimin Tian, Haitao Shang, Yichi Chen, Bolin Wu, Chunyue Wang, Xiaodong Wang, Wen Cheng Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of ChinaCorrespondence: Wen Cheng, Department of Ultrasound, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang Province, 150081, People’s Republic of China, Tel +86 13313677182, Fax +86 451 85718392, Email hrbchengwen@163.comBackground: Apoptosis resistance of hepatocellular carcinoma (HCC) often leads to treatment failure. Nonetheless, overcoming the resistance of HCC to apoptosis by inducing necroptosis of tumor cells to bypass the apoptotic pathway may be a promising treatment strategy. Sonodynamic therapy (SDT) has broad prospects in disease treatment because of its noninvasive characteristic and spatiotemporal control. The combination of SDT and shikonin in the treatment of HCC is expected to be a new tumor treatment method that can overcome apoptosis resistance.Methods: In this study, the antitumor effect was evaluated using normal liver cell line WRL68, HCC cell line HepG2 and HepG2 xenograft mouse models. Indocyanine green (ICG) was loaded on nanobubbles (NBs) to construct ICG-loaded nanobubbles (ICG-NBs). Combined sonosensitizer nanoplatforms with ultrasound (US) to achieve efficient SDT, the combination of SDT and shikonin in treating HCC can activate shikonin-induced necroptosis. As a result, tumor cells that produced apoptosis resistance were destroyed by necroptosis.Results: The results indicated a successful preparation of ICG-NBs with a uniform particle size of 273.0 ± 118.9 nm spherical structures. ICG-NB-mediated SDT, in combination with shikonin treatment, inhibited the viability, invasion, and migration of tumor cells. SDT + shikonin treatment group caused a substantial increase in necroptotic cells. The increased degree of tumor necrosis and the upregulated expression of receptor-interacting protein 3 kinase were observed in vivo studies, which indicated that the antitumor effect was accompanied by enhanced necroptosis in the SDT + shikonin treatment group.Conclusion: ICG-NB-mediated SDT combined with shikonin inhibits the growth of HCC by increasing the necroptosis of tumor cells. Therefore, this combination therapy is a promising treatment strategy against the specific cancer.Keywords: sonodynamic therapy, hepatocellular carcinoma, necroptosis, shikonin, sonosensitizer

Yichi Chen,1– 3 Bolin Wu,1– 3 Haitao Shang,1– 3 Yucao Sun,1– 3 Huimin Tian,1– 3 Huajing Yang,1– 3 Chunyue Wang,1– 3 Xiaodong Wang,1– 3 Wen Cheng1– 3 1Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China; 2Department of Interventional Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China; 3Institute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin, 150081, People’s Republic of ChinaCorrespondence: Wen Cheng, Department of Ultrasound, Department of Interventional Ultrasound, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang Province, 150081, People’s Republic of China, Tel +86 13313677182, Fax +86 451 85718392, Email chengwen@hrbmu.edu.cnBackground: Despite the clinical efficacy of immunotherapy in treating malignant tumors, its effectiveness is often hampered by the immunosuppressive nature of the tumor microenvironment (TME). In this study, we propose the design of a nanoscale ultrasound contrast agent capable of triggering macrophage polarization and immunogenic cell death (ICD) for the treatment of hepatocellular carcinoma (HCC) through sonodynamic treatment (SDT) and immunotherapy.Methods: The re-educator (designated as ICG@C3F8-R848 NBs) is composed of the Toll-like receptor agonist resiquimod (R848) and the sonosensitizer Indocyanine green (ICG), utilizing nanobubbles (NBs) as carriers. The technique known as ultrasound-targeted nanobubble destruction (UTND) employs nanosized microbubbles and low-frequency ultrasound (LFUS) to ensure accurate drug delivery and enhance safety.Results: Following intravenous delivery, ICG@C3F8-R848 NBs have the potential to selectively target and treat primary tumors using SDT in conjunction with ultrasonography. Importantly, R848 can enhance antitumor immunity by inducing the polarization of macrophages from an M2 to an M1 phenotype.Conclusion: The SDT-initiated immunotherapy utilizing ICG@C3F8-R848 NBs demonstrates significant tumor suppression effects with minimal risk of systemic toxicity. The utilization of this self-delivery re-education technique would contribute to advancing the development of nanomedicine for the treatment of hepatocellular carcinoma.Keywords: hepatocellular carcinoma, synergistic sono-immunotherapy strategy, tumor-associated-macrophage

Xiang Li,1,* Shanghua Xiao,2,* Nina Filipczak,3 Satya Siva Kishan Yalamarty,3 Hongming Shang,4 Jing Zhang,2 Qin Zheng2 1National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China; 2Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China; 3Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, USA; 4Department of Biochemistry & Chemical Biology, Vanderbilt University, Nashville, TN, USA*These authors contributed equally to this workCorrespondence: Jing Zhang; Qin Zheng, Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, 330004, People’s Republic of China, Email jing.zhang@jxutcm.edu.cn; 20060903@jxutcm.edu.cnAbstract: Neutrophil extracellular traps (NETs) are large DNA reticular structures secreted by neutrophils and decorated with histones and antimicrobial proteins. As a key mechanism for neutrophils to resist microbial invasion, NETs play an important role in the killing of microorganisms (bacteria, fungi, and viruses). Although NETs are mostly known for mediating microbial killing, increasing evidence suggests that excessive NETs induced by stimulation of physical and chemical components, microorganisms, and pathological factors can exacerbate inflammation and organ damage. This review summarizes the induction and role of NETs in inflammation and focuses on the strategies of inhibiting NETosis and the mechanisms involved in pathogen evasion of NETs. Furthermore, herbal medicine inhibitors and nanodelivery strategies improve the efficiency of inhibition of excessive levels of NETs.Graphical Abstract: Keywords: neutrophil extracellular traps, inflammation, targeted inhibition, nanotherapy, herbal medicine

Haoshaqiang Zhang,1,* Hua Shang,1,2,* Zhigang Wang,1 Kun Li1 1Department of Orthopedics Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China; 2Department of Human Resources, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhigang Wang, Department of Orthopedics Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, No. 91, Tianchi Road, Tianshan District, Urumqi, 830001, People’s Republic of China, Tel +86-9918563146, Email guanjie2023yundong@163.comPurpose: To analyze the independent associations of miRNA-146a and miRNA-223 with rheumatoid arthritis (RA) and evaluate their predictive values for RA.Patients and Methods: A total of 68 RA patients were selected as cases, and meanwhile 68 patients with a traumatic knee condition were selected as controls by matching to the cases according to sex and age at the ratio of 1:1. The independent associations of miRNA-146a and miRNA-223 with RA were identified by binary logistic regression analysis. Receiver operating characteristic (ROC) curve was used to evaluate their predictive values for RA.Results: MiRNA-146a and miRNA-223 expression levels in both synovial tissues and serums were statistically higher in cases than in controls, and their expression levels in serums were not statistically different from those in synovial tissues in both cases and controls. The expression levels of miRNA-146a and miRNA-223 in synovial tissues were independently associated with RA, as well as the expression levels of miRNA-146a and miRNA-223 in serums. The area under curve (AUC) of combination of miRNA-146a and miRNA-223 in synovial tissues for the prediction of RA was 0.910 [95% confidence interval (CI): 0.863– 0.962], and the AUC of combination of miRNA-146a and miRNA-223 in serums was 0.904 (95% CI: 0.851– 0.957). Their difference was not statistically significant (P=0.873), but the AUC of combination prediction was statistically higher than those of individual predictions (synovial tissues: 0.910 vs 0.773, P=0.005, 0.910 vs 0.788, P=0.009; serums: 0.904 vs 0.766, P=0.005, 0.904 vs 0.784, P=0.011).Conclusion: MiRNA-146a and miRNA-223 in both synovial tissues and serums could be applied in predicting RA, and their combination could elevate the predictive value significantly.Keywords: rheumatoid arthritis, MiRNA-146a, MiRNA-223, synovial tissues, serums, predictive values

This paper analyses spectropolarimetric observations of the classical T Tauri star (CTTS) GM Aurigae collected with SPIRou, the near-infrared spectropolarimeter at the Canada–France–Hawaii Telescope, as part of the SLS and SPICE Large Programs. We report for the first time results on the large-scale magnetic field at the surface of GM Aur using Zeeman Doppler imaging. Its large-scale magnetic field energy is almost entirely stored in an axisymmetric poloidal field, which places GM Aur close to other CTTSs with similar internal structures. A dipole of about 730 G dominates the large-scale field topology, while higher order harmonics account for less than 30 per cent of the total magnetic energy. Overall, we find that the main difference between our three reconstructed maps (corresponding to sequential epochs) comes from the evolving tilt of the magnetic dipole, likely generated by non-stationary dynamo processes operating in this largely convective star rotating with a period of about 6 d. Finally, we report a |$5.5\sigma$| detection of a signal in the activity-filtered radial velocity data of semi-amplitude |$110\pm 20$|  m s |$^{-1}$|  at a period of |$8.745\pm 0.009$|  d. If attributed to a close-in planet in the inner accretion disc of GM Aur, it would imply that this planet candidate has a minimum mass of |$1.10 \pm 0.30\, M_\mathrm{Jup}$| and orbits at a distance of |$0.082 \pm 0.002$|  au. [ABSTRACT FROM AUTHOR]

Yun Shu,1,* Hui Li,2,* Hongjuan Shang,1 Jun Chen,1 Xiaoxing Su,2 Wei Le,1 Yan Lei,2 Liming Tao,1 Cailiang Zou,1 Wendy Wu2 1Department of Medical Oncology, Third People’s Hospital of Jiujiang City, Jiujiang 332000, People’s Republic of China; 2Berry Oncology Corporation, Fuzhou 350200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wendy Wu Email wujy3261@berryoncology.comYun Shu Email shuyun1972@163.comObjective: ROS1 fusions have been identified in 1– 2% of non-small-cell lung cancer (NSCLC) patients; they are validated as a driver of carcinogenesis and could be subjected to inhibition by crizotinib. However, previous studies suggested a variable progression-free survival (PFS) ranging from 9.1 to 20.0 months for crizotinib treatment in ROS1-rearranged NSCLC. Here, we reported a 45-year-old female diagnosed with stage IVB lung adenocarcinoma with multiple lymph nodes and bone metastasis carrying a novel MPRIP-ROS1 fusion, which was identified by RNA-based NGS (next-generation sequencing) and was sensitive to crizotinib treatment.Materials and Methods: A targeted NGS panel was used to analyze genomic DNA and total RNA isolated from formalin-fixed paraffin-embedded (FFPE) tissue block of the patient. An RNA fusion panel based on amplicon sequencing was designed for detection fusion variation. Fusion results were validated using reverse transcriptase polymerase chain reaction and Sanger sequencing.Results: We reported a novel MPRIP-ROS1 fusion identified in this advanced lung adenocarcinoma case. The rearrangement was generated by exons 1– 21 of MPRIP at chr17: p11.2 joined to exons 35– 43 of ROS1 at chr6: q22.1, which retained an intact kinase domain of ROS1. The primary tumor and metastatic lymph nodes were eliminated on computed tomographic (CT) scan imaging after 2 months’ crizotinib treatment, and the multiple bone metastatic lesions were significantly relieved according to bone scintigraphy images. To date, the treatment has lasted 16 months, and the patient is still in follow-up showing sustained response to crizotinib.Conclusion: The study identified a novel MPRIP-ROS1 fusion that was sensitive to crizotinib, which provided a new driver of lung adenocarcinoma and potential therapeutic target for crizotinib. It also expanded NSCLC treatment of ROS1 rearrangement and highlighted the importance of genetic testing for precise treatment decision-making.Keywords: MPRIP-ROS1 fusion, advanced lung adenocarcinoma, sensitive to crizotinib, next-generation sequencing

Shengnan Wang,1,2,* Jing Wu,1,* Congcong Guo,3 Hongxia Shang,4 Jinming Yao,4 Lin Liao,4,5 Jianjun Dong6 1Laboratory of Endocrinology, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 2Department of Occupational Disease, Yantai Shan Hospital, Yantai, People’s Republic of China; 3Department of Endocrinology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 4Department of Endocrinology and Metabolism, The First Affiliated Hospital of Shandong First Medical University, Jinan, People’s Republic of China; 5Department of Endocrinology and Metabology, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 6Department of Endocrinology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin LiaoDepartment of Endocrinology and Metabolism, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, People’s Republic of ChinaTel +86 151 6888 8260Fax +86 531 8296 3647Email liaolin@sdu.edu.cnJianjun DongDepartment of Endocrinology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, People’s Republic of ChinaTel +86 137 9112 2910Fax +86 531 8296 7544Email cwc_ll@sdu.edu.cnPurpose: The conventional interventions of anaplastic thyroid carcinoma (ATC) patients are mainly through surgery, chemotherapy, and radiotherapy; however, it is hardly to improve survival rate. We aimed to investigate the differential expressed genes (DEGs) between ATC and normal thyroid gland through bioinformatics analysis of the microarray datasets and find new potential therapeutic targets for ATC.Methods: Microarray datasets GSE9115, GSE29265, GSE33630, GSE53072, and GSE65144 were downloaded from Gene Expression Omnibus (GEO) database. Compared with the normal tissue, GEO2R was conducted to screen the DEGs in each chip under the condition of |log FC| > l, adjusted P‐values (adj. P) < 0.05. The Retrieval of Interacting Genes (STRING) database was used to calculate PPI networks of DEGs with a combined score > 0.4 as the cut-off criteria. The hub genes in the PPI network were visualized and selected according to screening conditions in Cytoscape software. In addition, the novel genes in ATC were screened for survival analysis using Kaplan–Meier plotter from those hub genes and validated by RT-qPCR.Results: A total of 284 overlapping DEGs were obtained, including 121 upregulated and 161 downregulated DEGs. A total of 232 DEGs were selected by STRING database. The 50 hub genes in the PPI network were chosen according to three screening conditions. In addition, the Kaplan–Meier plotter database confirmed that high expressions of ANLN, CENPF, KIF2C, TPX2, and NDC80 were negatively correlated with poor overall survival of ATC patients. Finally, RT-qPCR experiments showed that KIF2C and CENPF were significantly upregulated in ARO cells and CAL-62 cells when compared to Nthy-ori 3– 1 cells, TPX2 was upregulated only in CAL-62 cells, while ANLN and NDC80 were obviously decreased in ARO cells and CAL-62 cells.Conclusion: Our study suggested that CENPF, KIF2C, and TPX2 might play a significant role in the development of ATC, which could be further explored as potential biomarkers for the treatment of ATC.Keywords: anaplastic thyroid carcinoma, bioinformatics analysis, Gene Expression Omnibus database, differential expressed genes