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Qian Cao,1,* Ruijie Zhou,2,* Songlin Guo,3 Kai Meng,4 Xiaojuan Yang,5 Miao Liu,1 Bin Ma,6 Chunxia Su,5 Xiangguo Duan2 1The First School of Clinical Medicine, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 2School of Inspection, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 3Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Yinchuan, 750004, People’s Republic of China; 4Traditional Chinese Medicine Hospital of Ningxia Medical University, Yinchuan, 750003, People’s Republic of China; 5School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 6Department of Oncology Surgery, the First People’s Hospital of Yinchuan, Yinchuan, 750004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunxia Su, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China, Email 1651085195@qq.com Xiangguo Duan, School of Inspection, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China, Email 2455281549@qq.comBackground: Tumor vaccines have achieved remarkable progress in treating patients with various tumors in clinical studies. Nevertheless, extensive research has also revealed that tumor vaccines are not up to expectations for the treatment of solid tumors due to their low immunogenicity. Therefore, there is an urgent need to design a tumor vaccine that can stimulate a broad anti-tumor immune response.Methods: In this work, we developed a nanovaccine (NP-TCL@APS), which includes nanoparticles loaded with colorectal cancer tumor cell lysates (TCL) and Astragalus polysaccharides (APS) into poly (lactic-co-glycolic acid) to induce a robust innate immune response. The NP-TCL@APS was identified by transmission electron microscopy and Malvern laser particle size analyzer. The killing and immune activation effects of NP-TCL@APS were evaluated in vitro. Finally, safety and anti-tumor efficacy were evaluated in the colorectal cancer tumor-bearing mouse model.Results: We found that NP-TCL@APS was preferentially uptaken by DC and further promoted the activation of DC in vitro. Additionally, nanoparticles codelivery of TCL and APS enhanced the antigen-specific CD8+ T cell response and suppressed the growth of tumors in mouse models with good biocompatibility.Conclusion: We successfully prepared a nanovaccine termed NP-TCL@APS, which can promote the maturation of DC and induce strong responses by T lymphocytes to exert anti-tumor effects. The strategy proposed here is promising for generating a tumor vaccine and can be extended to various types of cancers.Keywords: colorectal cancer, nanovaccine, PLGA, Astragalus polysaccharide, tumor cell lysates (TCL)

Bingjie Ma,1 Pengyi Hou,2 Ran Liu,3 Aijun Cang,1 Limei Zhao4 1Department of Pharmacy, People’s Hospital of Liaoning Province, Shenyang, 110010, People’s Republic of China; 2SCIEX Analytical Instrument Trading Co, Shanghai, 200000, People’s Republic of China; 3School of Food and Drug, Shenzhen Polytechnic, Shenzhen, 518000, People’s Republic of China; 4Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, 110010, People’s Republic of ChinaCorrespondence: Limei Zhao, Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, 110010, People’s Republic of China, Email lmzhao19@163.comBackground: Chemotherapy-induced myelosuppression (CIM) is a common adverse reaction with a high incidence rate that seriously affects human health. Shengyu Decoction (SYD) is often used to treat CIM. However, its pharmacodynamic basis and therapeutic mechanisms remain unclear.Purpose: This study aimed to clarify the active components and mechanisms of SYD in CIM.Methods: LC-QTOF/MS was used to identify the absorbable components of SYD. A series of network pharmacology methods have been applied to explore hub targets and potential mechanisms. Molecular docking was used to identify the binding ability of potential active ingredients and hub targets. Finally, in vitro experiments were performed to validate these findings.Results: In this study, 33 absorbable prototype components were identified using LC-QTOF/MS. A total of 62 possible targets of SYD in myelosuppression were identified. KEGG pathway enrichment analyses showed that some signaling pathways such as PI3K-Akt and HIF-1 may be the mechanisms by which it functions. Among them, we verified the PI3K-Akt pathway. 6 Hub proteins were screened by Protein–protein interaction (PPI) network analysis. Molecular docking results showed that four absorbable components in SYD showed good binding with six Hub targets. The effectiveness of the four predicted compounds and the mechanism were verified in vitro. It has also been shown that the active component could promote the proliferation of bone marrow stromal cells (BMSCs) and block apoptosis of BMSCs, which may be related to the PI3K-Akt pathway. This result is consistent with the network pharmacology approach and molecular docking predictions.Conclusion: Our results provided not only the candidate active component of SYD, but also a new insights into mechanism of SYD in the treatment of CIM. Keywords: Shengyu decoction, SYD, myelosuppression, network pharmacology, molecular docking, active components, mechanism

Lei K, Ma B, Shi P, et al. OncoTargets and Therapy. 2020;13:299–307. At the authors request, we, the Editor and Publisher of the journal OncoTargets and Therapy have retracted the published article. Following publication of the article, the authors raised concerns about the duplication of images from Figures 2, 3, 4 and 5 with images from unrelated articles. Specifically, Images from Figure 2A have been duplicated with images from Figure 2A from Li L, Liu J-D, Gao G-D, Zhang K, Song Y-W, Li H-B. Puerarin 6″-O-xyloside suppressed HCC via regulating proliferation, stemness, and apoptosis with inhibited PI3K/AKT/mTOR. Cancer Med. 2020;9:6399–6410. https://doi.org/10.1002/cam4.3285; Figure 3H from Hu X, Zou W, Liu D, Qin G, Jiang L. RETRACTED ARTICLE: The Down-Regulation of TrkB Alleviates the Malignant Biological Behavior and Cancer Stem-Like Property of Laryngeal Cancer. Cancer Manag Res. 2020;12:6865–6875. https://doi.org/10.2147/CMAR.S260693; Figure 1E from Wang W, Gou X, Xue H, Liu K. Ganoderan (GDN) Regulates The Growth, Motility And Apoptosis Of Non-Small Cell Lung Cancer Cells Through ERK Signaling Pathway In Vitro And In Vivo. Onco Targets Ther. 2019;12:8821–8832. https://doi.org/10.2147/OTT.S221161; Figure 4B from Chen X, Yang X, Mu J, Yue C. Ligustrazine inhibits the viability and motility of colon cancer cells. Transl Cancer Res. 2020;9(5):3203–3213. https://doi.org/10.21037/tcr-20-940; Figure 1B from Wang R, Zhu X, Wang Q, et al. The anti-tumor effect of taxifolin on lung cancer via suppressing stemness and epithelial-mesenchymal transition in vitro and oncogenesis in nude mice. Ann Transl Med. 2020;8(9):590. https://doi.org/10.21037/atm-20-3329; and Figure 1C from Zhou J, Jiang Y-Y, Chen H, Wu Y-C, Zhang L. Tanshinone I attenuates the malignant biological properties of ovarian cancer by inducing apoptosis and autophagy via the inactivation of PI3K/AKT/mTOR pathway. Cell Prolif. 2020; 53:e12739. https://doi.org/10.1111/cpr.12739. The image for Figure 3A, SCC-15, Control, has been duplicated with the image for Figure 6A, Control from Zhang K-q, Chu X-d. GANT61 plays antitumor effects by inducing oxidative stress through miRNA-1286/RAB31 axis in osteosarcoma. Cell Biol Int. 2021;45:61–73. https://doi.org/10.1002/cbin.11467. The image for Figure 4C, p65 fluorescence, SCC-15, ICA (5 µM), has been duplicated with the image for Figure 7J, Hep3B, sg-NC from Pu J, Huang Y, Fang Q, et al. Hypoxia-induced Fascin-1 upregulation is regulated by Akt/Rac1 axis and enhances malignant properties of liver cancer cells via mediating actin cytoskeleton rearrangement and Hippo/YAP activation. Cell Death Discov. 2021;7:385. https://doi.org/10.1038/s41420-021-00778-5. The image for Figure 5B, Ki67, Control, has been duplicated with the image for Figure 6D, CD44, Control for Li N, Cheng C, Wang T. MiR-181c-5p Mitigates Tumorigenesis in Cervical Squamous Cell Carcinoma via Targeting Glycogen Synthase Kinase 3β Interaction Protein (GSKIP). Onco Targets Ther. 2020;13:4495–4505. https://doi.org/10.2147/OTT.S245254. The authors were cooperative and responded to our queries but were unable to provide a satisfactory explanation for how the images came to be duplicated or provide satisfactory original data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the authors requested to retract the article and the Publisher and Editor agreed with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Bangzhen Ma,1,2 Yisheng Zhao,3 Xiaoli Liu,4 Mengping Huo,2 Jinghong Wang,2 Jiwei Ma,2 Yang Zhang,2 Chengkun Qin1,2 1Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China; 2Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 3School of Pharmaceutical Sciences, Key Laboratory for Natural Active Pharmaceutical Constituents Research in Universities of Shandong Province, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong, 250353, People’s Republic of China; 4Department of Hernia and Abdominal Wall Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, People’s Republic of ChinaCorrespondence: Chengkun Qin; Yang Zhang, Shandong Provincial Hospital, 324 Jingwu Road, Huaiyin District, Jinan City, Shandong Province, People’s Republic of China, Email qinchengkun_slyy@163.com; zhangyang@sdfmu.edu.cnBackground: Though nanomedicine-based photothermal therapy (PTT) has demonstrated promising prospect in tumor treatment due to its high therapeutic efficiency and controllable range, the overexpression of heat shock proteins (HSPs) during PTT can lead to intracellular thermal resistance and reduce its effectiveness. Reactive oxygen species (ROS), followed by the application of chemodynamic therapy (CDT) and photodynamic therapy (PDT), can eliminate HSPs and overcome thermal resistance. However, the tumor microenvironment, including hypoxia and glutathione (GSH) overexpression, impedes the production of ROS and therapeutic efficacy of CDT and PDT. Therefore, we proposed a multifunctional nanoplatform (HMPB@TCPP-Cu) driving PTT/ PDT/ CDT synergistic therapy for tumor treatment via modulating ROS and HSPs.Methods and Results: In this work, a novel nanoplatform (HMPB@TCPP-Cu) composed of O2/PTT supplier HMPB (hollow mesoporous Prussian blue) and the loaded PDT/CDT agent (TCPP-Cu2+) was prepared. HMPB acts as an photothermal converter, effectively raising the tumor temperature and inducing apoptosis. HMPB is also a potent catalase-like nanozyme, which can catalyze hydrogen peroxide into oxygen and reduce tumor hypoxia, thus elevating the efficiency of ROS production and the effectiveness of PDT with the wing of sonosensitizer-TCPP. The intracellular glutathione(GSH) was depleted by Cu2+ and •OH was generated along with the Cu2+/Cu+ converting and Cu+-mediated Fenton-like reaction. Subsequently, the increased levels of ROS effectively eliminate intratumoral thermal resistance. The HMPB@TCPP-Cu has achieved synergistic PTT/PDT/CDT for hepatoblastoma treatment and significant inhibition of tumor growth was detected both in vitro and in vivo.Conclusion: This study presents a multifunctional nanoplatform that combines photothermal/ chemodynamic/ photodynamic therapy for efficient hepatoblastoma treatment via modulating ROS and HSPs. Collectively, this study provides an appealing strategy in the cleavage of thermal resistance and a novel assistance and enhancement on thermal-related therapies.Keywords: photothermal therapy, heat shock protein, reactive oxygen species, photodynamic therapy, chemodynamic therapy

Ma B, Ma J, Yang Y, et al. Onco Targets Ther. 2020;13:3411–3423. At the author’s request, we, the Editors and Publisher of OncoTargets and Therapy, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figure 1. Specifically, The images shown in Figure 1D show duplicated and unexpected features which indicate the original images may have been altered. The authors responded to our queries but were unable to provide an explanation for the duplicated images or provide satisfactory data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the authors requested to retract the article and the Editor and Publisher agreed with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Yilin Li,1,* Tingting Wang,2,* Beibei Ma,2 Shangyue Yu,1 Hailuan Pei,1 Shiqiu Tian,1 Yingying Tian,1 Chuang Liu,1 Xinyue Zhao,1 Zeping Zuo,2 Zhibin Wang1,2 1School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Beijing Tongrentang Technology Co., LTD. Pharmaceutical Factory, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhibin Wang; Zeping Zuo, Beijing Tongrentang Technology Co., LTD. Pharmaceutical Factory, No. 20S 3rd Ring Road Middle, Beijing, 100071, People’s Republic of China, Email wangzhibin4804@126.com; zepingzuo@126.comPurpose: Xianglian Zhixie Tablet (XLZXT), a classical traditional Chinese medicine formulation, is commonly used to treat Ulcerative Colitis (UC) in China. However, the therapeutic mechanisms of XLZXT for UC have yet to be fully understood. This study aimed to investigate the curative benefits of XLZXT and its associated mechanisms for healing UC in mice.Methods: In the present study, the 1% dextran sulfate sodium (DSS) solution was used to establish the UC model in C57BL/6N mice. To investigate the therapeutic effects of XLZXT on DSS-induced UC mice, several parameters were measured, including DAI score, colon length, spleen index, pathological changes in colon tissue, and levels of inflammatory factors in plasma and colon tissue. By investigating the gut microbiota, assessing the levels of intestinal mucosal protein expression, and looking at the proteins involved in the TLR4/MyD88/NF-B p65 signaling pathway, the mechanisms of XLZXT impact on UC were investigated. Mouse feces were examined for patterns of gut microbiota expression using high-throughput sequencing of 16S rRNA.Results: XLZXT effectively alleviated UC symptoms and colon pathological damage in DSS-induced UC mice. It improved body weight loss, stool consistency, and hematochezia, while also repairing colon damage. Moreover, it down-regulated pro-inflammatory cytokines (such as TNF-α, IL-1β, and IL-6), and up-regulated anti-inflammatory cytokines (such as IL-10). XLZXT also increased the expression of MUC-2, Occludin and ZO-1, while decreasing the expression of NF-κB, MyD88 and TLR4. Additionally, it regulated gut microbiota disorder by increasing the abundance of beneficial bacteria and reducing the adhesion of intestinal harmful bacteria.Conclusion: XLZXT demonstrated therapeutic effects on DSS-induced UC mice. The mechanisms may be associated with repairing the intestinal mucosal barrier, regulating the TLR4/MyD88/NF-κB p65 signaling pathway, and restoring the balance of gut microbiota.Plain Language Summary: This is the first study to probe the therapeutic potential of XLZXT for UC. Our findings indicated that XLZXT could effectively alleviate the clinical symptoms of UC and in-depth apparently modify the levels of relevant cytokines in the organism to maintain the system homeostasis. Our results suggested that XLZXT might treat DSS-induced UC by repairing the intestinal mucosa barrier, regulating the TLR4/MyD88/NF-κB p65 signaling pathway, and restoring gut microbiota balance.Graphical Abstract: Keywords: ulcerative colitis, TCM, TLR4/MyD88/NF-кB p65 signaling pathway, gut microbiota

Jingjing Fan, Yunjian Tang, Kunming Wang, Shu Yang, Binlin Ma Department of Breast and Thyroid Surgery, Cancer Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of ChinaCorrespondence: Binlin Ma, Cancer Hospital Affiliated to Xinjiang Medical University, 789 Suzhou East Street, Xincheng District, Urumqi, Xinjiang, People’s Republic of China, Tel +86-991-7819082, Email mbldoctor@126.comObjective: The effect of chemotherapy in patients with breast cancer (BC) is uncertain. This study attempted to analyze serum microRNAs (miRNAs) in NAC resistant and sensitive BC patients and develop a miRNA-based nomogram model. To further help clinicians make treatment decisions for hormone receptor-positive patients.Methods: A total of 110 BC patients with NAC were recruited and assigned in sensitive and resistant group, and 4 sensitive patients and 3 resistant patients were subjected to high-throughput sequencing. The functions of their target genes were analyzed by GO and KEGG. Five BC-related reported miRNAs were selected for expression pattern measurement by RT-qPCR and multivariate logistic analysis. The nomogram model was developed using R 4.0.1, and its predictive efficacy, consistency and clinical application value in development and validation groups were evaluated using ROC, calibration and decision curves.Results: There were 44 differentially-expressed miRNAs in resistant BC patients. miR-3646, miR-4741, miR-6730-3p, miR-6831-5p and miR-8485 were candidate for resistance diagnosis in BC. Logistic multiple regression analysis showed that miR-4741 (or = 0.30, 95% CI = 0.08– 0.63, P = 0.02) and miR-6831-5p (or = 0.48, 95% CI = 0.24– 0.78, P = 0.01) were protective factors of BC resistance. The ROC curves showed a sensitivity of 0.884 and 0.750 for miR-4741 and miR-6831-5P as markers of resistance, suggesting that they can be used as independent risk factors for BC resistance. The other 3 miRNAs can be used as calibration factors to establish the risk prediction model of resistance in BC. In risk model, the prediction accuracy of resistance of BC is about 78%. 5-miRNA signature diagnostic models can help clinicians provide personalized treatment for NAC resistance BC patients to improve patient survival.Conclusion: MiR-4741 and miR-6831-5p are independent risk factors for breast cancer resistance. This study constructed a nomogram model of NAC resistance in BC based on 5 differentially-expressed serum miRNAs.Keywords: breast cancer, neoadjuvant chemotherapy, drug resistance, serum microRNAs, nomogram model, 5-miRNAs, GO and KEGG enrichment analyses

Jianwei Liu,1,* Minmin Sun,2,* Kunpeng Fang,3,* Jie Wang,1,* Bowen Ma,1 Li Song,1 Ting Liu,1 Ming Tang,4 Kui Wang,1 Yong Xia4 1Department of Hepatic Surgery II, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 2Department of Hepatic Surgery I, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 3Department of Special Treatment I, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 4Department of Hepatic Surgery IV, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong Xia, Department of Hepatic Surgery (IV), Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), #225 Changhai Road, Shanghai, 200438, People’s Republic of China, Tel +86-2181875005, Fax +86-2165562400, Email xia.yong@126.com Kui Wang, Department of Hepatic Surgery (II), Eastern Hepatobiliary Surgery Hospital, Navy Medical University, #225 Changhai Road, Shanghai, 200438, People’s Republic of China, Tel\Fax +86-2181875514, Email wangkuiykl@163.com

Wu P, Wang PL, Ma B, et al. Cancer Manag Res. 2018;10:4759–4771. The authors wish to advise that the published version of this article contains spelling errors. The text “randomixed control trail” in Figure 1 on page 4761, should read “randomized control trial”. The word “Beggar’s” used in the Publication bias section, line two, on page 4764 and for the caption of Figure 10, on Page 4767, should read “Begg’s”. The authors apologize for any confusion this may have caused. The journal wishes to advise readers that they have investigated the concerns for this article as indicated in the previously published Expression of Concern. The authors have now addressed these concerns and there are no further issues regarding the integrity of the article.

Jianwei Liu,1,* Minmin Sun,2,* Kunpeng Fang,3,* Jie Wang,1 Bowen Ma,1 Li Song,1 Ting Liu,1 Ming Tang,4 Kui Wang,1 Yong Xia4 1Department of Hepatic Surgery II, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 2Department of Hepatic Surgery I, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 3Department of Special Treatment I, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 4Department of Hepatic Surgery IV, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong Xia, Department of Hepatic Surgery (IV), Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), #225 Changhai Road, Shanghai, 200438, People’s Republic of China, Tel +86-2181875005, Fax +86-2165562400, Email xia.yong@126.com Kui Wang, Department of Hepatic Surgery (II), Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), #225 Changhai Road, Shanghai, 200438, People’s Republic of China, Email wangkuiykl@163.comPurpose: To investigate the effect of different liver resection modalities on the prognosis of left lateral lobe hepatocellular carcinoma (HCC) patients.Methods: 315 patients with HCC on left lateral lobe were divided into open left lateral lobectomy (LLL) group (n=249) and open left hepatectomy (LH) group (n=66). The differences in long-term prognosis between two groups were compared.Results: The results showed that narrow resection margin (Hazard Ratio (HR):1.457, 95% Confidential Interval (CI): 1.038– 2.047; HR:1.415, 95% CI: 1.061– 1.887), tumor diameter > 5 cm (1.645, 1.161– 2.330; 1.488, 1.123– 1.971), multiple tumors (2.021, 1.330– 3.073; 1.987, 1.380– 2.861), and microvascular invasion (MVI) (1.753, 1.253– 2.452; 1.438, 1.087– 1.902) are independent risk factors for overall survival (OS) and tumor recurrence (TR), while liver resection modality is not. After propensity score matching, liver resection modality is not an independent risk factor for OS and TR. Further analysis revealed that wide resection margins were achieved in all patients in the LH group but only 59.0% patients in the LLL group. The OS and TR rates were not significantly different between wide patients with resection margins in LLL group and LH group (P=0.766 and 0.919, respectively), but significantly different between patients with narrow resection margins in LLL group and LH group (P=0.012 and 0.017, respectively).Conclusion: Liver resection modality is not an independent risk factor for the prognosis of patients with HCC on the left lateral lobe as long as wide margins are obtained. Nevertheless, with narrow margins, patients who underwent LH rather than LLL did better.Keywords: hepatocellular carcinoma, left lateral hepatic lobe, left lateral lobectomy, left hepatectomy, prognosis

Yuhan Wang,1 Zhenyu Yin,1 Lei Gao,1 Bin Ma,1 Jianming Shi,1 Hao Chen2 1Lanzhou University Second Hospital, Lanzhou, 730030, People’s Republic of China; 2Department of Surgical Oncology, Key Laboratory of the Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu Province, People’s Republic of ChinaCorrespondence: Hao Chen, Tel +8615009467790, Fax +8609315109551, Email ery_chenh@lzu.edu.cnAbstract: Metastasis to the liver, as one of the most frequent metastatic patterns, was associated with poor prognosis. Major drawbacks of conventional therapies in liver metastasis were the lack of metastatic-targeting ability, predominant systemic toxicities and incapability of tumor microenvironment modulations. Lipid nanoparticles-based strategies like galactosylated, lyso-thermosensitive or active-targeting chemotherapeutics liposomes have been explored in liver metastasis management. This review aimed to summarize the state-of-art lipid nanoparticles-based therapies in liver metastasis management. Clinical and translational studies on the lipid nanoparticles in treating liver metastasis were searched up to April, 2023 from online databases. This review focused not only on the updates in drug-encapsulated lipid nanoparticles directly targeting metastatic cancer cells in treating liver metastasis, but more importantly on research frontiers in drug-loading lipid nanoparticles targeting nonparenchymal liver tumor microenvironment components in treating liver metastasis, which showed promise for future clinical oncological practice.Keywords: liver neoplasms, neoplasm metastasis, liposomes, tumor microenvironment

Qi Zhang,1,* Wenjuan Yan,1,* Yingjie Zhu,2,* Nan Jing,1 Shanmei Wang,1 Youhua Yuan,1 Bing Ma,1 Junhong Xu,1 Yafei Chu,1 Jiangfeng Zhang,1 Qiong Ma,1 Baoya Wang,1 Wenbo Xu,1 Liqiang Zhu,3 Ying Sun,2 Caiqin Shi,4 Juan Fang,5 Yi Li,1 Shengqun Liu6 1Department of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Zhengzhou, People’s Republic of China; 2Department of Clinical Microbiology, Henan No.3 Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 3Department of Clinical Microbiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 4Department of Microbiology Laboratory, KingMed Diagnostics Group Co., Ltd, Zhengzhou, People’s Republic of China; 5Department of Research and Development, Autobio Diagnostics Co., Ltd, Zhengzhou, People’s Republic of China; 6Department of Anesthesia and Perioperative Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Zhengzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi Li; Shengqun Liu, Department of Anesthesia and Perioperative Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Weiwu Road 7, Zhengzhou, Henan, 450003, People’s Republic of China, Tel +8613526882118, Fax +8637187160318, Email liyilabmed@henu.edu.cn; tim2002627@163.comPurpose: To evaluate the performance of five widespread commercial products for colistin and polymyxin B susceptibility testing in China for mcr-positive and -negative Escherichia coli and Klebsiella pneumoniae.Methods: A total of 132 E. coli and 83 K. pneumoniae strains (including 68 mcr-1-positive E. coli and 28 mcr-8-positive K. pneumoniae) were collected. We analysed the performance of colistin susceptibility (with Vitek 2 and Phoenix M50) and the performance of polymyxin B susceptibility (with DL-96II, MA120, and a Polymyxin B Susceptibility Test strip; POL E-strip). Broth microdilution was used as the gold standard. Categorical agreement (CA), essential agreement (EA), major error (ME), and very major error (VME) were calculated for comparisons.Results: For E. coli, the total CA, EA, ME, and VME to colistin were as follows: Vitek 2, 98.5%/98.5%/0%/2.9%; and Phoenix M50, 98.5%/97.7%/0%/2.9%. The total CA, EA, ME, and VME to polymyxin B were as follows: POL E-strip, 99.2%/63.6%/1.6%/0%; MA120, 70.0%/-/0%/58.8%; and DL-96II, 80.2%/-/1.6%/36.8%. Only Vitek 2 and Phoenix M50 presented satisfactory performances for mcr-1-positive E. coli. For K. pneumoniae, the total CA, EA, ME, and VME to colistin were as follows: Vitek 2, 73.2%/72.0%/0%/61.6%; and Phoenix M50, 74.7%/74.7%/0%/58.3%. The total CA, EA, ME, and VME to polymyxin B were as follows: POL E-strip, 91.6%/74.7%/2.1%/16.7%; MA120, 92.8%/-/2.1%/13.9%; and DL-96II, 92.2%/-/2.1%/8.3%. All systems were unsatisfactory for mcr-8-positive K. pneumoniae. When the susceptibility of mcr-negative strains was tested, all systems presented excellent performance.Conclusion: Vitek 2 and Phoenix M50 with colistin for E. coli showed acceptable performance regardless of mcr-1 expression, while DL-96II, MA120, and the POL E-strip performed worse for mcr-1-positive strains. Furthermore, mcr-8 greatly affected the performance of all systems with both colistin and polymyxin B for K. pneumoniae isolates.Keywords: polymyxin B, colistin, mobilised colistin resistance, broth microdilution, susceptibility testing, semi-automated systems

Miaomiao Han,1,2 Bo Ma,3 Ruifang She,4 Yan Xing,5 Xiaohong Li1 1Department of Neurology, Jinan Central Hospital, Shandong University, Jinan City, People’s Republic of China; 2Encephalopathy Department, Zibo Hospital of Integrated Traditional Chinese and Western Medicine, Zibo City, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of Bengbu Medical College, Bengbu City, People’s Republic of China; 4Department of Neurology, Tai’ an City Central Hospital, Tai’ an City, People’s Republic of China; 5Zibo Center for Disease Control and Prevention, Zibo City, People’s Republic of ChinaCorrespondence: Xiaohong Li, Department of Neurology, Jinan Central Hospital, Shandong University, No. 105, Jiefang Road, Jinan City, Shandong Province, 250013, People’s Republic of China, Tel + 86 13370582096, Email lxh5231@126.comPurpose: This retrospective observational study was conducted to determine the correlations between serum CXCL9/12 and the severity of acute ischemic stroke (AIS).Methods: Total 138 patients with AIS were enrolled in the study. These patients underwent Brain CT on admission and blood samples were collected. Serum CXCL9 and CXCL12 were detected by ELISA assay. The correlations of serum CXCL9/12 with AIS was analyzed based on Oxfordshire Community Stroke Project (OCSP) classification, Trial of Org 10,172 in acute stroke treatment (TOAST) classification, National Institutes of Health Stroke Score (NIHSS) score, infarct volume, and modified Rankin scale (mRS) score.Results: Compared with the controls, patients with AIS had higher levels of serum CXCL9 and CXCL12. Logistic regression analysis determined that CXCL9 and CXCL12 were independent risk factors for AIS. In addition, the increased serum CXCL9 and CXCL12 were associated with TOAST classification, NIHSS score, and infarct volume. However, serum CXCL9 and CXCL12 were not associated with functional outcomes (mRS score). CXCL9 and CXCL12 both exhibited a high diagnostic value in AIS.Conclusion: Serum CXCL9 and CXCL12 were elevated in patients with AIS, closely correlated with the severity of AIS.Keywords: acute ischemic stroke, CXCL9, CXCL12, stroke severity, NIHSS score

Chao Gao,1 Li Li,2 Xixin Jin,1 Xinyu Song,1 Huiling Li,1 Xiaoli Xu,1 Chao Dong,1 Binlin Ma1 1State Key Laboratory of Pathogenes, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Breast and Thyroid Surgery, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2State Key Laboratory of Pathogenes, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Gynecology and surgery, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, People’s Republic of ChinaCorrespondence: Chao Dong; Binlin Ma, State Key Laboratory of Pathogenes, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Breast and Thyroid Surgery, Affiliated Cancer Hospital of Xinjiang Medical University, No. 789 of East Suzhou Street, Urumqi, 830000, People’s Republic of China, Tel +860991-7968088, Fax +860991-7968111, Email dc_dongchao@outlook.com; mabinlinmbl@21cn.comAim: This study investigated the role and mechanism of insulin-like growth factor 2-IGF2BP2 in breast cancer.Methods: IGF2BP2 is overexpressed in MDA-MB-231 human breast cancer cells. Thus, RNA sequencing was used to analyze the differentially expressed genes, Cell Counting Kit-8 was used to detect cell proliferation, and a Transwell assay was used to assess cell invasion. Following on from the RNA sequencing results, Interferon-induced protein with tetratricopeptide repeats 2 (IFIT2), chemokine C-C motif ligand 20 (CCL20), chemokine C-C motif ligand 5 (CCL5), and chemokine C-X-C motif ligand 10 (CXCL10) regulated by IGF2BP2 were subjected to real-time reverse transcriptase-polymerase chain reaction verification.Results: After IGF2BP2 overexpression, 67 genes were up-regulated, and 87 genes were down-regulated. The gene with the most significant up-regulation was homeobox protein 1 (PROX1), and the gene with the most significant down-regulation was Acidic β-crystallin 4 (CRYBA4). The most enriched gene ontology (GO) terms of up-regulated differentially expressed genes are protein binding and cell membrane and of down-regulated differentially expressed genes they are ion binding, cytoplasm, and response to virus. Kyoto Encyclopedia of Genes and Genomes analysis showed that the up-regulated differential genes were mainly enriched in protein processing, the endoplasmic reticulum, and the regulation of actin cytoskeleton, while down-regulated differential genes were mainly enriched in rheumatoid arthritis, chemokine signaling pathways, toll-like receptor signaling pathways, tumor necrosis factor signaling pathways, cytokine-cytokine receptor interaction, and Notch signaling pathways. IGF2BP2 overexpression significantly promoted the proliferation and invasion of breast cancer cells (P < 0.01). Compared with the control group, the IGF2BP2 overexpression group had significantly increased expressions of IFIT2, CCL20, and CXCL10 (P < 0.05).Conclusion: IGF2BP2 may promote the invasion and proliferation of human breast cancer cells by up-regulating breast cancer-related genes, such as IFIT2, CCL20, and CXCL10.Keywords: breast cancer, RNA-binding protein, IGF2BP2, bioinformatics

Tingting Chen,1,2,&ast; Bingxiang Ma,1,2,&ast; Shi Lu,1,2 Lupeng Zeng,1,2 Huaying Wang,1,2 Wanhua Shi,1,2 Linying Zhou,3 Yaokun Xia,4 Xi Zhang,1 Jing Zhang,5 Jinghua Chen1 1School of Pharmacy, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China; 2Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China; 3Electron Microscopy Facility, Public Technology Service Center, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China; 4Key Laboratory of the Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China; 5Department of Chemical Biology, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, Fujian Province, 350002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinghua Chen, School of Pharmacy, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China, Tel +86 591-22862016, Fax +86 591-22862016, Email cjh_huaxue@126.com; xz@fjmu.edu.cnPurpose: In recent years, a variety of nanoparticles with excellent anticancer and delivery properties have emerged for cancer therapy. However, potential toxicity, high production cost and complex preparation procedures have been obstacles to their use in biomedicine. Here, we obtained cucumber-derived nanovesicles (CDNVs) at high yield and low cost by simple juicing and ultracentrifugation. The anticancer effects of CDNVs were evaluated in vitro and in vivo.Methods: Transmission electron microscope, nanoparticle tracking analysis and laser particle size analysis were used to characterize the morphology, diameter and zeta potential of CDNVs, respectively. The anticancer effects of CDNVs in vitro were evaluated by MTT and apoptosis assays. The mechanism was further explored by measuring the protein levels of signal transducer and activator of transcription 3 pathway, reactive oxygen species, cell cycle distribution and caspase activity. In-vivo anticancer efficacy was evaluated by measuring tumor volume and weight of mice in three different treatment groups (CDNVs, cucurbitacin B and PBS).Results: CDNVs inhibited proliferation of human non-small cell lung cancer cells by suppressing signal transducer and activator of transcription 3 activation, generating reactive oxygen species, promoting cell cycle arrest, and activating the caspase pathway. These CDNVs exhibited strong anticancer effects both in vitro and in vivo, and reduced the rate of tumor growth without obvious toxicity to mouse visceral organs. Compared with an equivalent dose of cucurbitacin B, CDNVs exerted stronger anticancer effects in vitro and in vivo.Conclusion: These results demonstrate that CDNVs suppress tumor growth. This study addresses the development of cancer therapeutic drugs using plant-derived nanovesicles that are cost-efficient, simple to produce in high yields, and provide an alternative approach to drug isolation that may help advance sustainability of medicinal plants.Keywords: ROS, STAT3, cucurbitacin B, anticancer

Can Hao &ast;, Bingjie Ma &ast;, Nan Gao, Tian Jin, Xiaoming Liu Pain Management Center, Shanghai Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 210092, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoming Liu, Pain Management Center, Shanghai Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665# Kongjiang Road, Shanghai, 210092, People’s Republic of China, Tel +86-17721213706, Fax +86-21-25078707, Email brightlxm@gmail.comPurpose: Recent studies showed promotion of astrocyte autophagy in the spinal cord would provide analgesic effects. Silent information regulator T1 (SIRT1) and α subunit of peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1α) are two master regulators of endogenous antioxidant defense and mitochondrial biogenesis. They play vital roles in both autophagy and neuropathic pain (NP). Our previous study showed that TSPO agonist Ro5-4864 elicited potent analgesic effects against NP, but the mechanisms remain unclear. This study aims to investigate the effects of TSPO agonist Ro5-4864 on autophagy and nuclear SIRT1/PGC-1α signaling in spinal dorsal horn.Methods: A rat model of L5 spinal nerve ligation (SNL) was adopted. Rats were randomly assigned to the Sham group, the SNL group, the Ro (TSPO agonist Ro5-4864) group and the Ro+3-MA group. The behavior assessments were conducted at baseline, on Day 1, 3, 7 and 14 after SNL. The autophagy-related proteins (ATG7, Beclin1, LC3, and P62) in spinal dorsal horn were assayed and the nuclear SIRT1/PGC-1α and downstream factors were analyzed.Results: Ro5-4864 alleviated the mechanical allodynia induced by SNL (P < 0.01 vs the SNL group), which could be totally abrogated by autophagy inhibitor 3-MA (P < 0.01 vs the Ro group). SNL induced elevated ATG7 (P < 0.01), Beclin1 (P < 0.01) and LC3-II/LC3-I (P < 0.01) contents and P62 accumulation (P < 0.01) on Day 7 and Day 14, which suggested an autophagy flux impairment. Ro5-4864 augmented ATG7 (P < 0.01), Beclin1 (P < 0.01) and LC3-II/LC3-I (P < 0.05) with decreased P62 (P < 0.01), which indicated a more fluent autophagic process. These effects were also totally abrogated by 3-MA (P < 0.01). Furthermore, Ro5-4864 activated the spinal nuclear SIRT1/PGC-1α signaling pathway.Conclusion: TSPO improved both autophagy impairment and mitochondrial biogenesis, which may provide a new strategy for the treatment of NP.Keywords: translocator protein, TSPO, neuropathic pain, autophagy, silent information regulator T1, SIRT1, α subunit of peroxisome proliferator-activated receptor-γ coactivator-1, PGC-1&#x03B1

Jiaxuan Yang,1,&ast; Bin Ma,2,&ast; Hao Zhong,1 Yue Zhang,1 Jiang Zhu,1 Yong Ni1 1Pain Department, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Medical College, Soochow University, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiang Zhu; Yong Ni, Tel +86 18013575733, Email zhujiangsz@126.com; niyong2148@163.comPurpose: This study was to assess the safety and effectiveness of ultrasound-guided percutaneous A1 pulley release by acupotomy on unembalmed cadavers.Materials and Methods: Sixty digits (from six cadavers, three male and three female) were split into two groups using stratified randomization. All procedures were completed by a single doctor with rich experience in ultrasound-guided treatment. In the acupotomy group, the A1 pulley was released under ultrasound-guided by a needle-knife; while in the needle group, the A1 pulley was released under ultrasound-guided by a 21-gauge needle. Two groups completed six thumbs and 24 fingers, respectively. Another anatomist, blinded to the two techniques, assessed the safety, including the minimum distance between the incision and the neurovascular; flexor tendon, neurovascular and A2 pulley injury or not. Completeness release of the A1 pulley was recorded as effectiveness.Results: No neurovascular or A2 pulley injuries were recorded. However, the incision of the thumb in both groups biased to the radial side (P < 0.05), while the incision of the finger biased to the ulnar side (P < 0.05). No significant flexor tendon injury was found, and only five cases (16.7%) had minor scratches in the acupotomy group; while in the needle group, 15 cases had minor scratches and lacerations occurred in three cases. The flexor tendon injury rate was 60%. Compared with the needle, ultrasound-guided acupotomy release is safer (P < 0.05). The ultrasound-guided acupotomy technique was significantly more likely to result in a complete A1 pulley release compared to the needle technique (28 of 30 [93.3%] versus 11 of 30 [36.7%]; P < 0.05).Conclusion: Ultrasound-guided percutaneous A1 pulley release by acupotomy is a safe and effective technique. When releasing the thumb by ultrasound-guided, be careful not to bias to the radial side to avoid neurovascular injury, while when releasing a finger, be careful not to bias to the ulnar side.Keywords: ultrasonography, acupotomy, trigger finger, anatomical study

Shushu Qian,1,&ast; Xuan Han,2,&ast; Xiaocao Sha,1,&ast; Fang Tian,1 Hong Huang,1 Pengjun Jiang,1 Guoshun Huang,1 Bangyun Ma,1 Hong Zhang,1 Yiye Zhu,1 Xuemei Sun1 1Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 2School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuemei Sun, Tel +86-25-86617141, Fax +86-25-86518690, Email 13913911666@qq.comPurpose: Cimicifuga dahurica (C. dahurica), which has been used in traditional oriental medicine for a long period, was reported to exert extensive antitumor activity, but the effect and molecular biological mechanism of C. dahurica on multiple myeloma (MM) has not been elaborated. Tumor-associated macrophages (TAMs) exhibit a sustained polarization between tumor killing M1 subtype and tumor supporting M2 subtype. And a lower ratio of M1/M2 is associated with tumor angiogenesis, proliferation and invasion. We explored the inhibitory effect of the aqueous extract of the root of C. dahurica (CRAE) on tumor growth by reprogramming macrophage polarization in the tumor microenvironment.Methods: Mice bearing SP2/0 multiple myeloma were treated with CRAE. Western blotting (WB), immunohistochemistry (IHC) and immunofluorescence staining were utilized to assess tumor growth and TAM populations. Macrophages were depleted by injection of clodronate liposomes to determine and measure the role of CRAE as an anti-tumor agent by targeting macrophages. To simulate tumor microenvironment, MM cells H929 and TAMs were co-cultured using the transwell co-culture system. By using CRAE as an immunoregulator in M2-like macrophages, we analyzed CRAE-treated macrophage-associated surface markers and cytokines by flow cytometry and WB.Results: The results indicated that CRAE treatment could reduce tumor burden of MM mice and a high degree of M1-like macrophages infiltration was detected in tumor tissues. In vitro co-culture system, CRAE significantly promoted the polarization of M2 to M1 phenotype, which led to the increase in apoptosis of myeloma cells. It was found that the M1 polarization induced by CRAE depended on the TLR4-MyD88-TAK1-NF-κB signal transduction.Conclusion: This study elucidated the anticancer mechanism of the aqueous extract of C. dahurica (CRAE) through reprogramming macrophage polarization and highlighted that CRAE could act as a potential novel option for cancer immunotherapy.Keywords: Cimicifuga dahurica, tumor-associated macrophages, macrophage polarization, multiple myeloma, tumor microenvironment

Wu P, Wang PL, Ma B, et al. Cancer Manag Res. 2018;10:4759–4771 The Editor and Publisher of Cancer Management and Research are issuing an Expression of Concern for the published article. Following publication concerns have been raised over the integrity of the articles content. As we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. The authors have been notified about this Expression of Concern.

Baoya Wang,1 Wenjuan Dong,2 Liyan Ma,3 Yonghui Dong,4 Shanmei Wang,1 Youhua Yuan,1 Qiong Ma,1 Junhong Xu,1 Wenjuan Yan,1 Jing Nan,1 Qi Zhang,1 Wenbo Xu,1 Bing Ma,1 Yafei Chu,1 Jiangfeng Zhang,1 Li Li,1 Yi Li1 1Department of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Zhengzhou, 450003, Henan, People’s Republic of China; 2Department of Clinical Microbiology, Xicheng District Pingan Hospital, Beijing, 100035, People’s Republic of China; 3Department of Clinical Microbiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 4Department of Osteology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Zhengzhou, 450003, Henan, People’s Republic of ChinaCorrespondence: Yi Li; Li LiDepartment of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Weiwu Road 5, Zhengzhou, 450003, Henan, People’s Republic of ChinaTel +8637165580484Fax +8637187160318Email liyilabmed@henu.edu.cn; hnykylili@126.comObjective: This study aimed to investigate the prevalence, genetic diversity and clinical characteristics of Clostridium perfringens isolates from hospitalized clinical diarrheal patients.Methods: A prospective study was conducted on 1108 patients with diarrhea during hospitalization. Stool samples were cultured for C. perfringens, and the toxin genes were detected by PCR. The available clinical data of 112 patients were analyzed to study the clinical features of various isolates. Multi-locus sequence typing (MLST) was performed to assess phylogenetic relationship between different isolates.Results: A total of 153 (13.8%) isolates were obtained from patients’ stools. C. perfringens type F (49.0%) was the major toxin type in the isolates, followed by type A (n = 59, 38.6%) and type C (n = 14, 9.2%). Patients older than 50 years and those with underlying diseases of cancer, hepatobiliary system, and ulcerative colitis (UC) were more predisposed to C. perfringens type F and type A infection than to type C. The patients infected with type C experienced more severe clinical symptoms compared to those with type A infection. There was a significant association between type FC and foodborne gastrointestinal (GI) diseases (p = 0.018), between type FP and antibiotic-associated diarrhea (AAD) (p < 0.001), and between type A and sporadic diarrhea (SD) (p < 0.001). Phylogenetic analysis indicated that type F isolates carrying a chromosomal cpe gene mainly belonged to ST77 (6/15 isolates). Type F isolates with cpe gene on a plasmid exhibited high genetic diversity.Conclusion: High prevalence and considerable genetic diversity of C. perfringens type F were found in clinical diarrheal patients. Elderly people and patients with cancer, hepatobiliary diseases or UC, or suspected of having food poisoning (FP) may be targeted for routine testing of C. perfringens toxin genes and may benefit from early detection of C. perfringens type C isolates that cause more severe clinical symptoms.Keywords: Clostridium perfringens, toxin type, clinical characteristics, prevalence, MLST

Baorui Ma,* Linnuo Pang,* Pingqing Huang, Jie Bai, Zhiqin Zhang, Huimin Wu, Mengru Cai, Jin Yang, Yuchen Xu, Xingbin Yin, Changhai Qu, Jian Ni School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changhai Qu; Jian NiSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Higher Education Zone, Fangshan District, Beijing, 102488, People’s Republic of ChinaEmail quchanghai@bucm.edu.cn; njtcm@263.netPurpose: To prepare the levocarnitine thermosensitive in situ gel (LCTG) and evaluate its effect on dry eye disease (DED).Methods: Draize eye irritation test and other examinations were used to evaluate the eye irritation after multiple administration of LCTG. The Schirmer test, fluorescein sodium staining, HE staining and TUNEL staining were used to detect the tear secretion, corneal injury, histopathological changes of the cornea and lacrimal gland, and the apoptosis rate of cornea epithelial cells after 3 days of the administration. The conjunctival goblet cell density was detected by PAS staining, and the expression levels of matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-9 (MMP-9) of corneal epithelial cells were detected by immunofluorescence staining after 7 days of the administration.Results: LCTG is non-irritating to rabbit eyes and has good biocompatibility. LCTG administration for 3 days can significantly increase the amount of tear secretion in mice with DED, promote corneal epithelial integrity and central corneal epithelium thickness recovery, and improve the pathological morphology and structure of corneal and lacrimal gland tissues, and reduce the apoptosis rate of the corneal epithelial cells. After 7 days of the administration, the preparation can promote the proliferation of conjunctival goblet cells and down-regulate the cornea expression levels of MMP-3 and MMP-9 in epithelial cells.Conclusion: The LCTG has a good curative effect on mice with DED, and the overall curative effect is better than that of levocarnitine solution.Keywords: levocarnitine, cornea, in situ gel, delivery, dry eye disease

Shishuai Wen,1,2,* Ning Qu,1,2,* Ben Ma,1,2,* Xiao Wang,1,2,* Yi Luo,1,2,* Weibo Xu,1,2 Hongyi Jiang,1,2 Yan Zhang,2,3 Yu Wang,1,2 Qinghai Ji1,2 1Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qinghai Ji; Yu WangDepartment of Head & Neck Surgery, Fudan University Shanghai Cancer Center, No. 270, Dong’an Road, Shanghai, 200032, People’s Republic of ChinaFax +021 6404 0207Email jq_hai@126.com; neck130@sina.comBackground and Objectives: Targeting cancer-associated fibroblast (CAF) is being explored as an approach to improve cancer therapies. The roles of CAF remain unclarified in malignant transformation of papillary thyroid cancer (PTC) into dedifferentiated thyroid cancer (DDTC). This study aimed to investigate correlations of CAF with dedifferentiation and clinicopathological characteristics of thyroid cancer.Materials and Methods: We applied three different mRNA-based CAF gene signatures to quantify CAF in our cohort, the Gene Expression Omnibus (GEO) cohort and The Cancer Genome Atlas (TCGA) cohort, and analyzed expression of α-SMA by immunohistochemistry in thyroid cancer. The CAF score was analyzed for its associations with clinicopathological characteristics, genetic mutations, tumor-associated signaling pathways and immune landscape.Results: The CAF score increased significantly in DDTCs compared with normal thyroid tissues and PTCs, and the α-SMA-positive CAFs were found enriched in DDTCs. The high CAF score showed a significant correlation with the anaplastic phenotype in DDTC and low thyroid differentiation score in PTC. Patients with a high CAF score remarkably increased the risk of aggressive outcomes in both DDTC and PTC. Furthermore, the CAF score was positively correlated with genetic mutations, oncogenic signaling pathways, the immune score and increased expression of tumor microenvironment (TME) target markers.Conclusion: Our findings suggest CAFs positively correlate with dedifferentiation and aggressive outcomes of thyroid cancer, and targeting CAFs as a therapeutic approach may benefit DDTC patients.Keywords: CAF, dedifferentiation, DDTC, PTC

Jing-Tao Zhou,1,* Jiang-Hao Liu,2,* Ting-Ting Song,2 Bo Ma,3 Nuermaimait Amidula,1 Chao Bai4 1General Surgery, The Seventh Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2General Surgery, Xinjiang Uygur Autonomous Region Eighth People’s Hospital, Urumqi, People’s Republic of China; 3General Surgery, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 4Department of Vascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chao BaiDepartment of Vascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, No. 137 South Liyushan Road, New District, Urumqi 830000, People’s Republic of ChinaTel +86 991-4364657Email baichao1981yww@163.comObjective: To investigate the anti-tumor effects of programmed cell death protein 1 (PD-1) scFv-secreting EGFR-chimeric antigen receptor-modified (CAR)-T cells against gastric cancer.Methods: Second-generation EGFR-CAR-T cells and fourth-generation PD-1 scFv-secreting EGFR-CAR-T cells were engineered. The anti-tumor activities of chimeric antigen receptor-modified (CAR)-T cells were analyzed in vitro by long-term co-culture with gastric cancer cells. The tumor scavenging capacity in vivo was evaluated in xenograft and PDX mouse models.Results: EGFR-CAR-T cells secreting PD-1 scFv showed enhanced long-term tumor cell killing capacity in vitro. These cells also showed significant anti-tumor effect in the subcutaneous xenograft model of gastric cancer as well as in the PDX model, and autocrine PD-1 antibody secretion significantly increased tumor infiltration of the CAR-T cells.Conclusion: EGFR-CAR-T cells secreting PD-1 scFv are highly effective against gastric cancer and offer new insights into anti-cancer immunotherapy.Keywords: EGLIF-CAR-T cells, PD-1 blocking antibodies, elimination, gastric cancer

Bingqiang Ma,* Jianxun Ma,* Yili Yang, Xueyuan He, Xinmin Pan, Zhan Wang, Yaowen Qian Department of General Surgery, Cancer Center, Key Laboratory for Diagnosis and Treatment of Gastrointestinal Cancer, Gansu Provincial Hospital, Lanzhou, Gansu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yaowen QianGeneral Surgery, Cancer Center, Key Laboratory for Diagnosis and Treatment of Gastrointestinal Cancer, Gansu Provincial Hospital, 204 Donggangxi Road, Chengguan District, Lanzhou, Gansu Province 730000, People’s Republic of ChinaTel +86 15293110056Email qyw2218@163.comBackground: miRNA, as a biological marker, had more and more attention in recent years due to the important role it plays in cancer. Currently, there are extensive studies on miRNAs, among which miR-330-3p is reported to be implicated in the pathophysiological processes of various cancers. However, little progress has been made in the mechanism of miR-330-3p in gastric cancer.Objective: To explore the expression and relevant mechanism of miR-330-3p and PRRX1 in gastric cancer (GC).Methods: Forty-five GC patients (study group), from whom paired GC and paracancerous tissues were collected, and another 45 healthy subjects (control group) who underwent physical examination during the same period were enrolled. In addition, GC cells and human gastric mucosa cells were purchased, and miR-330-3p-mimics, miR-330-3p-inhibitor, miR-NC, si-PRRX1, and sh-PRRX1 were transfected into MKN45, SGC7901 cell. QRT-PCR was employed to assess the miR-330-3p and PRRX1 expressions in the samples, and the cell expressions of PRRX1, GSK-3β, p-GSK-3β, β-catenin, p-β-catenin, cyclin D1, N-cadherin, E-cadherin and vimentin were evaluated by Western blot (WB). MTT, Transwell and wound-healing experiments were adopted to detect cell proliferation, invasion and migration.Results: MiR-330-3p was under-expressed, while PRRX1 was highly expressed in the serum of patients, both of which had an area under the curve (AUC) of more than 0.9. MiR-330-3p and PRRX1 were associated with tumor diameter, TNM staging, lymph node metastasis and differentiation of GC patients. Overexpression of miR-330-3p and inhibition of PRRX1 expression could suppress epithelial–mesenchymal transition (EMT), proliferation, invasion and apoptosis of cells. What is more, WB assay showed that overexpressed miR-330-3p and inhibited PRRX1 could inhibit the expression levels of p-GSK-3β, β-catenin, cyclin D1, N-cadherin and vimentin proteins, while elevating GSK-3β, p-β-catenin and E-cadherin protein expressions. Dual-luciferase reporter assay confirmed that there was a targeting relation between miR-330-3p and PRRX1. Furthermore, rescue experiments revealed that the cell proliferation, invasion, migration did not differ significantly between co-transfected miR-330-3p-mimics+sh-PRRX1, miR-330-3p-inhibitor+si-PRRX1 groups of MKN45 and SGC7901 and the miR-NC group (without transfected sequences).Conclusion: Overexpressed miR-330-3p can promote cell EMT, proliferation, invasion and apoptosis through inhibiting PRRX1-mediated Wnt/β-catenin signaling pathway, which is expected to be a potential therapeutic target for GC.Keywords: miR-330-3p, PRRX1, Wnt/β-catenin signaling pathway, biological function, GC

Chang-Shun Liu,1– 3 Li Chen,4 Yan-Nan Hu,1– 3 Jin-Lian Dai,4 Biao Ma,4 Qing-Fa Tang,1– 3 Xiao-Mei Tan1– 3 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, People’s Republic of China; 3Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology, Southern Medical University, Guangzhou 510515, People’s Republic of China; 4School of Pharmacy, Zunyi Medical University, Zunyi 563000, People’s Republic of ChinaCorrespondence: Li Chen; Xiao-Mei Tan Email zmu_cl@126.com; tanxm_smu@163.comPurpose: Ferulic acid (FA) is a natural compound which is used to treat insomnia. However, its use is limited because of its poor oral bioavailability caused by extremely rapid elimination. The current study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) to improve the oral delivery of FA and to enhance its hypnotic efficacy.Methods: FA-SMEDDS was prepared, and its morphology and storage stability were characterized. The formulation was also subjected to pharmacokinetic and tissue distribution studies in rats. The hypnotic efficacy of FA-SMEDDS was evaluated in p-chlorophenylalanine-induced insomnia mice.Results: FA-loaded SMEDDS exhibited a small droplet size (15.24 nm) and good stability. Oral administration of FA-SMEDDS yielded relative bioavailability of 185.96%. In the kidney, SMEDDS decreased the distribution percentage of FA from 76.1% to 59.4% and significantly reduced its metabolic conversion, indicating a reduction in renal elimination. Interestingly, FA-SMEDDS showed a higher distribution in the brain and enhanced serotonin levels in the brain, which extended the sleep time by 2-fold in insomnia mice.Conclusion: This is the first study to show that FA-loaded SMEDDS decreased renal elimination, enhanced oral bioavailability, increased brain distribution, and improved hypnotic efficacy. Thus, we have demonstrated that SMEDDS is a promising carrier which can be employed to improve the oral delivery of FA and facilitate product development for the therapy of insomnia.Keywords: insomnia, ferulic acid, oral administration, pharmacokinetics, SMEDDS

Ke Lei, 1 Bing Ma, 2 Ping Shi, 2 Che Jin, 3 Tan Ling, 1 Longjiang Li, 4 Xiangyi He, 5 Lunchang Wang 1 1Department of Stomatology, Central Hospital of Guangyuan, Guangyuan 628000, People’s Republic of China; 2Department of Respiratory, Central Hospital of Guangyuan, Guangyuan 628000, People’s Republic of China; 3Endodontics Department, Dental Hospital of Lanzhou, Lanzhou 730000, People’s Republic of China; 4State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, People’s Republic of China; 5Department of Prosthodontics, School of Stomatology, Lanzhou University, Lanzhou 730000, People’s Republic of ChinaCorrespondence: Ping ShiDepartment of Respiratory, Central Hospital of Guangyuan, Guangyuan 628000, People’s Republic of ChinaTel/Fax +86 839-3222256Email shi0036369692@163.comBackground: Oral squamous cell carcinoma (OSCC) is an aggressive malignancy worldwide. Icariin (ICA), an active ingredient of flavonoids, has been demonstrated to possess antitumor activity in diverse cancers. Whereas, the role of ICAin OSCC is still unclear.Methods: Herein, we investigated the anti-tumor effects of ICA in vitro and in vivo. CCK-8, colony formation and trans-well assay were used to examined viability, proliferation and invasion in SCC-9 and SCC-15 cell lines, respectively. Next, we tested the expression of toll-like receptor 4 (TLR4) and NF-κB P65 by western blot or immunofluorescence staining. Finally, we constructed a xenograft mice model to investigate the effect of ICA in vivo.Results: In vitro, ICA decreased the human oral squamous cells viability, proliferation and invasion in a concentration-dependent manner. Besides, ICA decreased the phosphorylation level of P65 and down-regulated TLR4 protein. In vivo, compared with control, ICA significantly suppressed the tumor size and weight. In addition, ICA downregulated the levels of Ki67 and VEGF markedly. Dramatically, ICA decreased the phosphorylation level of P65 in tumor tissues.Conclusion: Taken together, ICA could act as a anticancer drug against OSCC to mitigate the growth and invasion ability, the underlying mechanism may due to the down-regulation of TLR4/NF-κB signaling.Keywords: icariin, toll-like receptor 4, oral squamous cell carcinomas, NF-κB

Youhua Yuan, 1,* Junjie Wang, 2,* Zonghui Yao, 1,* Bing Ma, 1 Yi Li, 1 Wenjuan Yan, 1 Shanmei Wang, 1 Qiong Ma, 1 Jiangfeng Zhang, 1 Junhong Xu, 1 Li Li, 1 Yuming Wang, 1 Enguo Fan 1 1Department of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Zhengzhou, Henan 450003, People’s Republic of China; 2Clinical Laboratory, Luyi Zhenyuan Hospital, Zhoukou, Henan 477200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Enguo Fan; Yuming WangDepartment of Clinical Microbiology Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Weiwu Road 5, Zhengzhou, Henan 450003, People’s Republic of ChinaTel +8637165580484Fax +8637187160318Email enguofan@126.com; henanyuming@sina.comPurpose: The incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSIs) is increasing globally; however, little has been reported on the risk factors and outcomes of CRKP BSIs in central China. This study aimed to determine the clinical risk factors for CRKP BSIs and the outcomes of CRKP BSIs.Patients and Methods: We performed a case-control study of 239 patients with K. pneumoniae BSIs who were treated at Henan Provincial People’s Hospital between July 2017 and July 2018. The cases (n=98, 41%) had CRKP BSIs, and the controls (n=141, 59%) had non-carbapenem-resistant K. pneumoniae (non-CRKP) BSIs. Antimicrobial sensitivity was determined using automated broth microdilution and an agar disk diffusion method. Data were obtained from clinical and laboratory records. Multivariate logistic regression and Pearson chi-square tests were used to identify clinical factors and outcomes associated with carbapenem resistance.Results: Risk factors for carbapenem resistance included recent carbapenem use (odds ratio [OR]: 9.98, 95% confidence interval [CI]: 5.2– 17.1, P< 0.001), invasive procedures (OR: 11.1, 95% CI: 3.3– 37.7, P< 0.001), and pre-existing diseases of the digestive system (OR: 8.22, 95% CI: 1.73– 39.2, P=0.008). Treatment failure was more frequent in the cases (84.7%) than in the controls (32.6%).Conclusion: Exposure to antibiotics, especially carbapenems, and invasive procedures were the major risk factors for carbapenem resistance among patients with K. pneumoniae BSIs. Strict control measures should be implemented to prevent the emergence and spread of CRKP.Keywords: antimicrobial resistance, bacteremia, digestive system diseases, treatment failure

Hengli Yang,1,2,* Wenbin Cai,3,* Wei Lv,2 Ping Zhao,2 Yamei Shen,4 Longfang Zhang,1 Bin Ma,1 Lijun Yuan,2 Yunyou Duan,2 Kechun Yao11Department of Ultrasound Diagnosis, Air Force General Hospital, Beijing, People’s Republic of China; 2Department of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China; 3Special Diagnosis Department, General Hospital of Tibet Military Command, Lhasa, People’s Republic of China; 4Department of Ultrasound Diagnosis, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China *These authors contributed equally to this workCorrespondence: Yunyou DuanDepartment of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi’an 710038, People’s Republic of ChinaEmail duanyy@fmmu.edu.cnKechun YaoDepartment of Ultrasound Diagnosis, Air Force General Hospital, Beijing 100036, People’s Republic of ChinaEmail yaokc1959@hotmail.comBackground: Currently, effective detection and treatment of cutaneous malignant melanoma (CMM) still face severe challenges. Ultrasound molecular imaging as a noninvasive and easy-to-operate method is expected to bring improvements for tumor detection.Purpose: The aim of this research is to prepare novel phase-change ultrasound contrast agents, Nds-IR780, which can perform not only dual-mode molecule-targeted imaging but also targeted photothermal therapy for CMM.Methods: A double emulsion process was used to prepare the Nds-IR780. Then, the entrapment rate and drug loading of IR-780 iodide in Nds-IR780 were detected by high-performance liquid chromatography. The biocompatibility of Nds-IR780 was evaluated by a CCK-8 assay and the characteristics and stability of that were verified through the particle size analyzer, laser scanning confocal microscopy (LSCM) and transmission electron microscopy (TEM). The abilities of dual-mode molecule-targeted imaging and targeted photothermal therapy for Nds-IR780 were confirmed via the in vitro and in vivo experiments.Results: Nds-IR780 had good size distribution, polydispersity index, stability and biosafety. The in vitro and in vivo experiments confirmed that Nds-IR780 were capable of targeting CMM cells with high affinity (22.4±3.2%) and facilitating dual-mode imaging to detect the primary lesion and sentinel lymph nodes (SLNs) of CMM. Furthermore, the photothermal ablation of CMM mediated by Nds-IR780 was very effective in vivo.Conclusion: The newly prepared Nds-IR780 were observed to be effective targeted theranostic probe for the precise detection and targeted treatment of CMM.Keywords: CMM, dual-mode phase-change nanodroplets, targeted accurate diagnosis and treatment

Haifeng Song,1–3,* Ben Xu,1–3,* Cheng Luo,1–3 Zhenan Zhang,1–3 Binglei Ma,1–3 Jie Jin,1–3 Qian Zhang1–31Department of Urology, Peking University First Hospital, Beijing 100034, People’s Republic of China; 2Institute of Urology, Peking University, Beijing 100034, People’s Republic of China; 3National Research Center for Genitourinary Oncology, Beijing 100034, People’s Republic of China*These authors contributed equally to this workPurpose: This study aimed to investigate the significance of the controlling nutritional status (CONUT) score as a predictor for survival outcomes for non-metastatic renal cell carcinoma (RCC) patients.Methods: We retrospectively reviewed 325 patients who received surgical treatment for renal cell carcinoma between 2010 and 2012 at Peking University First Hospital. Patients were divided into two groups according to the optimal cut-off value of CONUT score. Kaplan–Meier method and log-rank test were used for survival analysis according to different CONUT groups. Cox proportional hazards regression models were performed to assess the prognostic value of clinicopathological parameters for overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) respectively.Results: The optimal cut-off value of CONUT score was 3. High CONUT score significantly correlated to higher tumor grade (P

Beibei Ma,1,* Jie Sheng,1,2,* Ping Wang,1 Zhongying Jiang,1,2 Entomack Borrathybay31College of Electronic and Information Engineering, Yili Normal University, Micro-nano Electric Sensing Technology and Bionic Devices Key Laboratory, Yining 835000, People’s Republic of China; 2Physics School of Nanjing University, Laboratory of Solid State Microstructures, Nanjing 210093, People’s Republic of China; 3College of Biology and Geography Sciences, Yili Normal University, Yining, Xinjiang, 835000, People’s Republic of China*These authors contributed equally to this work Background: Tumor metastasis is responsible for most cancer death worldwide, which lacks curative treatment.Purpose: The objective of this study was to eliminate tumor and control the development of tumor metastasis.Methods: Herein, we demonstrated a smart nano-enabled platform, in which 2-[2-[2-chloro-3-[(1,3-dihydro-3,3-dimethyl-1-propyl-2h-indol-2-ylidene)ethylidene]-1-cyclohexen-1-yl]ethenyl]-3,3-dimethyl-1-propylindolium iodide (IR780) and tirapazamine (TPZ) were co-loaded in poly(ϵ-caprolactone)-poly(ethylene glycol) (PEG-PCL) to form versatile nanoparticles (PEG-PCL-IR780-TPZ NPs).Results: The intelligence of the system was reflected in the triggered and controlled engineering. Specially, PEG-PCL not only prolonged the circulation time of IR780 and TPZ but also promoted tumor accumulation of nanodrugs through enhanced permeability and retention (EPR) effect. Moreover, reactive oxygen species (ROS) generated by IR780 armed by an 808 nm laser irradiation evoked a cargo release. Meanwhile, IR780, as a mitochondria-targeting phototherapy agent exacerbated tumor hypoxic microenvironment and activated TPZ for accomplishing hypoxia-activated chemotherapy. Most significantly, IR780 was capable of triggering immunogenic cell death (ICD) during the synergic treatment. ICD biomarkers as a “danger signal” accelerated dendritic cells (DCs) maturation, and subsequently activated toxic T lymphocytes.Conclusion: Eventually, antitumor immune responses stimulated by combinational phototherapy and hypoxia-activated chemotherapy revolutionized the current landscape of cancer treatment, strikingly inhibiting tumor metastasis and providing a promising prospect in the clinical application.Keywords: phototherapy, hypoxia-activated chemotherapy, IR780, tirapazamine, antitumor immune responsive, metastasis

Yigang Wang,1 Binrong Wang,1 Junnan Liang,2 Caixia Cui,3 Chang Ying,1 Fang Huang,4 Buyun Ma,1 Xiumei Zhou,1 Liang Chu21College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, People’s Republic of China; 2Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 3Department of Otorhinolaryngology, Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, People’s Republic of China; 4Department of Pathology, Zhejiang Provincal People’s Hospital, Hangzhou 310014, People’s Republic of ChinaBackground: Oncolytic virus can specifically replicate in and then lyse tumor cells, but seldom in normal cells. Further studies have shown the significant therapeutic effect of oncolytic virotherapy combining with other strategies, such as chemo-, radio-, and immunotherapy et al. In this study, we investigated the combinational effect of oncolytic virus ZD55-TRAIL and chemotherapy drug doxorubicin (DOX) on human laryngeal squamous cell carcinoma (LSCC).Methods: The effect of ZD55-TRAIL combined with DOX on cell growth was assessed in LSCC Hep2 cells and normal cells by MTT assay. Hochest 33342 staining was performed to observe cell morphological changes. Western blot was used to detect the expression of apoptotic activation proteins. The in vivo antitumor efficacy of combination treatment was estimated in laryngeal cancer xenograft models.Results: The combination of ZD55-TRAIL and DOX exhibited enhanced inhibitory effects on laryngocarcinoma cell growth, and had few side effects to normal cells in vitro. Chemotherapy drug increased the inducement of tumor cell apoptosis mediated by oncolytic virus. In vivo experiment confirmed that the combination treatment significantly inhibited Hep2 laryngocarcinoma xenografts growth in mice.Conclusion: The oncolytic viro-chemotherapy is a potent therapeutic approach for in vitro cytotoxicity evaluation of Hep2 cells and xenograft growth in vivo.Keywords: laryngocarcinoma, oncolytic virus, ZD55-TRAIL, doxorubicin

Xiaodong Wang,1 Jian Lu,1 Jisen Cao,2 Bozhao Ma,1 Chao Gao,1 Feng Qi1 1Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; 2Department of Hepatobiliary Surgery, Tianjin Third Center Hospital, Tianjin, China Background: Hepatocellular carcinoma (HCC) is known to feature several microRNA dysregulations. This study aimed to determine and investigate the prognostic value of microRNA (miRNA/miR)-18a and its role in regulating the progression of HCC.Methods: miR-18a expressions in human HCC tissues, pair-matched adjacent normal liver tissues as well as in HCC cell lines were determined by quantitative real-time PCR. The prognostic value of miR-18a was determined using Kaplan–Meier survival analysis and multivariable Cox regression assay. The ability of miR-18a in promoting HCC progression was verified in vitro.Results: miR-18a expressions in HCC tissues and cells were more than twice those of the normal control group (P

Pei Wu,1 Pengliang Wang,1 Bin Ma,2 Songcheng Yin,1 Yuen Tan,1 Wenbin Hou,1 Zhenning Wang,1 Huimian Xu,1 Zhi Zhu1 1Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang 110001, China; 2Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Dadong District, Shenyang 110042, Liaoning Province, China Background: Whether palliative gastrectomy combined with chemotherapy can improve the survival of patients with advanced gastric cancer remains controversial. We performed a meta-analysis to clarify whether palliative gastrectomy plus chemotherapy can benefit patients with incurable advanced gastric cancer and to explore the best candidates in this patient population. Methods: We searched the literature systematically using electronic databases including PubMed, EMBASE, and the Cochrane Library. And HRs and their 95% CIs were used to express the results for overall survival (OS) and progression-free survival (PFS). Results: One randomized controlled trial with 175 patients and 12 cohort studies with 2,193 patients were analyzed. The pooled HR for OS (HR=0.43, 95% CI=0.29–0.65, P

Jie Sheng,1,2 Beibei Ma,1 Qian Yang,1 Chao Zhang,2 Zhongying Jiang,1,2 Entomack Borrathybay3 1College of Electronic and Information Engineering, Yili Normal University, Micro-nano Electric Sensing Technology and Bionic Devices Key Laboratory, Yining 835000, China; 2Physics School of Nanjing University, Laboratory of Solid State Microstructures, Nanjing 210093, China; 3College of Biology and Geography Sciences, Yili Normal University, Yining 835000, Xinjiang, China Introduction: In recent years, near-infrared laser-induced photothermal therapy is being considered as a promising approach to kill tumors owing to its noninvasive nature and excellent antitumor efficiency. However, the lack of ideal photothermal agents hinders further development of this technology. Materials and methods: Aiming at solving this long-standing obstacle, we report here about the polyethylene glycol (PEG)-DA modified copper sulfide (CuS) nanoparticles (NPs) (PEG-DA-CuS NPs), a kind of semiconductor photothermal agents that show excellent photothermal stability and high heat conversion efficiency. Results and discussion: Owing to the surrounding PEG, the water solubility of CuS NPs was significantly improved when circulating in blood in the body. When the NPs reached the tumors and were irradiated by a 1,064 nm laser (1 W/cm2, 10 minutes), the local temperature increased above 90°C, triggering the retro Diels–Alder reaction. After the release of PEG chain, CuS NPs soon formed aggregates and enriched the tumor via the enhanced permeability and retention effect, promoting the efficacy of photothermal therapy. Conclusion: Therefore, we believe PEG-DA-CuS NPs are able to serve as a kind of cytotoxic and efficient photothermal agent to kill cancer. Keywords: CuS, PEG, retro Diels–Alder reaction, excellent photothermal stability, high heat conversion efficiency, aggregation in tumor

Yong Zhang,* Yalong Qi,* Axiang Wang, Baozhen Ma, Xiaomin Fu, Lingdi Zhao, Quanli Gao Department of Biotherapy, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China *These authors contributed equally to this work Abstract: Endometrial cancer is the most prevalent gynecological malignancy in the USA, and its treatment involves surgery, chemotherapy, and radiotherapy. Cytokine-induced killer (CIK) cell-based treatments have shown antitumor activity against several solid tumors. However, to the best of our knowledge, there are no reports yet of CIK immunotherapy in the treatment of endometrial cancer, and consequently, little is known about its efficacy and safety. Here, we report a case of an endometrial cancer patient receiving a combination treatment with CIK cells immunotherapy and chemotherapy. Assessment for clinical features was carried out after every two cycles of CIK immunotherapy and chemotherapy. No severe toxicity was observed after infusion of CIK cells. After 4 cycles of treatment, the patient achieved complete response and showed elevated Karnofsky Performance Status scores with an overall survival time of 13.6 months. The combination therapy improved the quality of life and prolonged patient survival time, which suggested that CIK cell therapy might be a potentially beneficial option for endometrial cancer. Keywords: cytokine-induced killer cells, endometrial cancer, immunotherapy, combination therapy

Barbara Ma,1 Chaitra Ujjani2 1Department of Medicine, 2Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, DC, USA Abstract: Impressive progress has been made in recent decades for advanced-stage follicular lymphoma with the availability of anti-CD20 monoclonal antibodies, initially rituximab and more recently obinutuzumab. Obinutuzumab is a unique, third-generation, fully humanized glycoengineered IgG1 type II anti-CD20 monoclonal antibody. It has been shown to have increased antitumor activity compared to rituximab in preclinical studies, including whole-blood B-cell depletion assays, xenograft models, and primate models. This has spurred on the development of obinutuzumab through Phase I/II trials as monotherapy and in combination with chemotherapeutic agents and other targeted therapies. Its efficacy compared to rituximab and in rituximab-refractory disease has led to its continued development and eventual approval for the treatment of follicular lymphoma. Here in this review, we highlight the design and development of obinutuzumab in the treatment of advanced stage grade 1–3A follicular lymphoma and its future directions. Keywords: follicular lymphoma, obinutuzumab, anti-CD20 monoclonal antibody