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Hongyu Duan,1,&ast; Yifan Zhou,2,&ast; Baikai Ma,1,&ast; Rongjun Liu,3 Tingting Yang,4 Hongling Chu,5 Zejun Huo,6 Hong Qi1 1Department of Ophthalmology, Peking University Third Hospital, Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Beijing, People’s Republic of China; 2Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 3Department of Ophthalmology, Peking University First Hospital, Beijing, People’s Republic of China; 4Department of Ophthalmology, Guangdong Provincial People’s Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 5Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, People’s Republic of China; 6Department of Traditional Chinese Medicine, Peking University Third Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Qi, Department of Ophthalmology, Peking University Third Hospital, Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, 49 North Garden Road, Haidian District, Beijing, 100191, People’s Republic of China, Email doctorqihong@163.com Zejun Huo, Department of Traditional Chinese Medicine, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, People’s Republic of China, Email huozejun@163.comBackground: Ocular pain is a prevalent symptom of dry eye disease (DED), which often accompanies potential psychological issues. The study aimed to explore whether acupuncture could improve ocular pain, mental state, and dry eye parameters in patients with DED.Methods: The non-randomized pilot study included 48 patients divided into two groups: the acupuncture group (n=27) and the 0.3% sodium hyaluronate (SH) group (n=21). Participants in the acupuncture group underwent treatments on six bilateral acupuncture points (BL1, BL2, ST1, LI 20, SI1 and SI3) 3 times per week for 4 weeks. Patients in the SH group received 0.3% SH 4 times per day for 4 weeks. Ocular pain was assessed using the numerical rating scale (NRS), and mental state was evaluated through the self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Ocular surface parameters, concentrations of inflammatory cytokines, and corneal nerve morphological indicators were measured at baseline, the first week, and the fourth week. Randomization procedures were not used in this study, and outcome assessors and statistical analysts were blinded.Results: Compared with baseline, both NRS scores (from 5.91 ± 1.52 to 1.94 ± 1.57) and ocular surface discomfort index (OSDI) scores (from 49.75 ± 14.92 to 29.64 ± 18.79) were decreased after 1 and 4 weeks of treatment in both groups (all p < 0.05). At 4 weeks, the acupuncture group showed significant improvements, including increased tear break-up time (TBUT) and corneal perception, decreased SAS and SDS scores, and reduced concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α concentration in tears (all p < 0.05). These changes were not observed in the SH group (all p > 0.05).Conclusion: Acupuncture treatment could improve ocular surface characteristics in patients with DED, and more importantly, it alleviates their ocular pain and depressive state. The anti-inflammatory effect of acupuncture may be involved in this process. Future research with larger, randomized controlled trials (RCTs) is necessary to confirm these findings and clarify the mechanisms involved.Keywords: acupuncture, dry eye disease, ocular pain, depression, inflammatory cytokines

Qian Cao,1,&ast; Ruijie Zhou,2,&ast; 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&ast;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

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

Yilin Li,1,&ast; Tingting Wang,2,&ast; 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&ast;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-&kcy;B p65 signaling pathway, gut microbiota

Wildfire plays an important role in restructuring bacterial and protist taxonomic and functional communities in forest ecosystems. Yet, the recovery of bacterial and protist communities following wildfire has not been rigorously investigated across long-term wildfire chronosequences. We compared changes in bacterial and protist alpha diversity, community composition, co-occurrence networks and determinant edaphic factors between burnt and unburnt (reference) soils at 11 different sites representing a 76-year wildfire chronosequence in Canadian boreal forests. The fire increased bacterial and protist alpha diversity and altered community composition (beta diversity) as compared to the site-specific controls during the early recovery stage (30 years) recovery stages. Bacterial and protist communities showed similar patterns of change across the wildfire chronosequence. The post-fire recovery of bacterial communities was associated with changes in soil chemical properties (e.g., nutrient status and pH) and vegetation succession. The protist community assembly was co-influenced by changes in bacterial communities and vegetation succession/soil properties. The concurrent recovery of bacterial and protist communities, and their influencing factors of vegetation and soil properties, imply the above- and belowground living communities are strongly linked in wildfire-perturbed forest ecosystems.

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,&ast; Minmin Sun,2,&ast; Kunpeng Fang,3,&ast; 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&ast;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), &num;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), &num;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

Jianwei Liu,1,&ast; Minmin Sun,2,&ast; Kunpeng Fang,3,&ast; Jie Wang,1,&ast; 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&ast;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), &num;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, &num;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.

Qi Zhang,1,&ast; Wenjuan Yan,1,&ast; Yingjie Zhu,2,&ast; 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&ast;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

Purpose(1) To identify bone-shape changes from baseline to 3-years after anterior cruciate ligament reconstruction (ACLR). (2) to assess association between changes in bone-shape from baseline to 6-months and changes in cartilage matrix and patient functions and symptoms from baseline to 3-years after ACLR.MethodsBilateral knees of 30 patients with unilateral ACL injuries were scanned at baseline, 6-months, 1-, 2-, and 3-years after ACLR. Bilateral knees of 13 controls were scanned at baseline, 1- and 3-years. Mean T1ρ and T2 values of each cartilage compartment were computed. Bone shape was quantified using statistical shape modeling (SSM) and 3D-MRI. Patient functions and symptoms were evaluated using Knee Injury and Osteoarthritis Outcome Score (KOOS).ResultsStatistically significant changes were observed in Femur 2 (medial femoral condyle [MF] shape), Femur 6 (intercondylar notch width), Tibia 1 (tibia plateau area), and Tibia 7 (medial tibia slope) over 3-years after ACLR. Statistically significant differences were observed between injured and control knees in several modes. Statistically significant correlations were found between changes in bone shape (ΔFemur 6, ΔFemur 8 [trochlea inclination and MF height], ΔTibia 1) from baseline to 6-months and that of cartilage T1ρ and T2 and KOOS from baseline to 3-years after ACLR.ConclusionBone shape remodeling occurs after ACLR, and early bone shape changes (within 6 months) correlated with cartilage matrix and patient outcomes at 3-years after ACLR. Bone shape can be a promising imaging biomarker that stratifies patients at high risk for post-traumatic osteoarthritis (PTOA).

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

1. This study evaluated the effects and mechanisms of action of the peptide gADP3 on hepatic inflammatory injury induced by lipopolysaccharide (LPS).2. Hepatic inflammatory injury was induced in geese by intraperitoneal injection of LPS and gADP3, and the adiponectin receptor agonist AdipoRon (positive control) was used for potential amelioration. Serum inflammatory factor levels, liver function-related biochemical indicators and oxidative stress-related biochemical parameters in the liver tissues were determined. The expression levels of adiponectin and its receptors, inflammation and oxidative stress-related genes and key signalling molecules involved in adiponectin, inflammation and oxidative stress signalling pathways in liver tissues were detected.3. The peptide gADP3 alleviated inflammatory cell infiltration and hepatic inflammatory changes, reversed the decrease in serum albumin (ALB), total protein (TP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) content or activity induced by LPS and increased the activity of the antioxidant enzymes CAT (catalase), SOD (superoxide dismutase) and GSH-Px (glutathione peroxidase).4. The peptide gADP3 upregulated the expression of antioxidant enzyme-related genes GCLC, HO-1 and NQO1 in liver tissues, decreased the levels of inflammatory factors like TNF-α, IL-1β, IL-6, IFN-γ and TGF-β and reduced mRNA expression levels of inflammatory-related genes TNF-α, IL-1β, iNOS and TGF-β. Additionally, it increased the mRNA and protein expression levels of adiponectin and its receptors, as well as key molecules in the adiponectin signalling pathway like AMPK and PPARα. In addition, gADP3 reversed the changes in mRNA or protein expression of inflammatory and oxidative stress signalling pathway-related genes P38MAPK, NF-κBP65, TLR4 and Nrf2 in liver tissues caused by LPS treatment.5. In conclusion, goose-derived adiponectin peptide gADP3, similar to the adiponectin receptor agonist AdipoRon, attenuated LPS-induced hepatic inflammatory injury in geese. [ABSTRACT FROM AUTHOR]

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