Liver cancers, majority of which are primary hepatocellular carcinoma (HCC), continue to be on the rise in the world. Furthermore, due to the lack of effective treatments, liver cancer ranks the 4 th most common cause of male cancer deaths. Novel therapies are urgently needed. Over last few years, immunotherapies, especially the checkpoint blockades and adoptive cell therapies of engineered T cells, have demonstrated a great potential for treating malignant tumors including HCC. In this review, we summarize the current ongoing research of antigen-specific immunotherapies including cancer vaccines and adoptive cell therapies for HCC. We briefly discuss the HCC cancer vaccine and then focus on the antigen-specific T cells genetically engineered with the T cell receptor genes (TCRTs) and the chimeric antigen receptor genes (CARTs). We first review the current options of TCRTs and CARTs immunotherapies for HCC, and then analyze the factors and parameters that may help to improve the design of TCRTs and CARTs to enhance their antitumor efficacy and safety. Our goals are to render readers a panoramic view of the current stand of HCC immunotherapies and provide some strategies to design better TCRTs and CARTs to achieve more effective and durable antitumor effects.

ObjectiveTo explore the relationships between dispositional mindfulness (DM) and their post-traumatic stress symptoms (PTSS) of emergency nurses, and the mediating effects of coping styles and emotional exhaustion (EE).MethodsA cross-sectional survey study was conducted to collect data on DM, coping styles, EE, and PTSS among 571 emergency nurses from 20 hospitals in Chongqing, China. Correlation and structural equation models (SEMs) were used to evaluate the relationship among variables.ResultsEmergency nurses with lower dispositional mindfulness, higher emotional exhaustion and preference for negative coping (NC) revealed more PTSS. The effect of NC on PTSS was partially mediated by emotional exhaustion. Negative coping and emotional exhaustion played concurrent and sequential mediating roles between dispositional mindfulness and PTSS.ConclusionThis study has made a significant contribution to existing literature. It was suggested to develop interventions aimed at enhancing mindfulness, reducing negative coping strategies, and alleviating emotional exhaustion, which may be effective at reducing or alleviating post-traumatic stress symptoms of emergency nurses.

To explore the effect of Joanna Briggs Institute (JBI) physical restraint standards in improving physical restraint in critical and emergency department patients. Enrolled 300 critical patients admitted in our hospital's emergency department from January to December 2019: 150 patients admitted January to June 2019 as control group and 150 patients admitted July to December 2019 as observation group. Routine restraints were applied in control group. Emergency department nurses in the observation group received thematic and practical JBI standardized training. This included pre-restraint assessment, principles of physical restraint, informed consent, using a restraint decision-making wheel, and alternatives to physical restraint. The incidence of restraint-associated adverse events (e.g., skin bruising, swelling) and restraint utilization rate were examined between 2 groups. The incidence of adverse events and the restraint utilization rate were significantly lower in the observation group ( P < .05). The application of JBI physical restraint standards for emergency department patients can effectively reduce the incidence of adverse events and the restraint utilization rate.

MicroRNAs (miRNAs) are highly conserved, noncoding small RNAs that regulate gene expression, and consequently several important functions including early embryo development, cell cycle, programmed cell death, cell differentiation, and metabolism. While there are no effective treatments available against hepatocellular carcinoma (HCC), some Chinese herbal medicines have been shown to regulate growth, differentiation, invasion, and metastasis of HCC. Many studies have shown that Chinese herbal medicines regulate the expression of miRNAs and this may be associated with their ability to control the development of HCC. In this article, the effects of Chinese herbal medicines on the expression of miRNAs and their functions in the regulation of HCC have been reviewed and discussed. miRNAs such as miRNA-221 and miRNA-222 mediated by Chinese herbal medicines may be good biomarkers and therapeutic targets for HCC.

Background and Aim: Several glypican 3 (hGPC3)-specific chimeric-antigen-receptor modified T cells (CARTs) are in trials for hepatocellular carcinoma (HCC), but most are constructed from one monoclonal antibody (mAb). It is unknown how targeting different hGPC3 epitopes will affect CART’s efficacy. The aim of this study is to develop novel effective CARTs by targeting different regions of hGPC3. Methods: BalB/C mice were immunized with hGPC3 protein to generate novel mAbs that targeted different regions of hGPC3. CARTs were then built from mAbs and their antitumor effect was studied. Results: Twenty-two mAbs were identified by ELISA. Fourteen of them bound HepG2 cells. Five mAbs were further characterized by immunohistochemical staining. Three of them (6G11, 8F8, and 12D7) were found to specifically stain HCC tumors but not adjacent normal tissues. The mAbs’ affinity was in the nanomolar range. 6G11 and 8F8 bound to hGPC3 N-(AA25-39) and C-(AA463-496) epitopes, respectively. 12D7 recognized a conformational epitope in the hGPC3 N-fragment (AA25-358). All CARTs built from the mAbs underwent expansion after GPC3+ cell stimulation. However, their effector function was significantly different. 8F8 CARTs possessed the strongest effector function. 6G11 CARTs experienced the greatest expansion, but with slightly weaker function. In contrast, 12D7 CARTs showed minimal effector function. Soluble hGPC3 did not activate CARTs or block CART activation by tumor cells. Adoptive transfer of 8F8 and 6G11, but not 12D7, CARTs generated complete regression of HCC xenografts in NSG mice. Conclusion: The three novel CARTs that target a membrane-distal N-epitope, a membrane-proximal C-epitope, or a conformational epitope of hGPC3 possessed different effector function and antitumor effects. CARTs targeting the hGPC3 N- or C specific epitope generated potent antitumor effects, while CARTs targeting an hGPC3-N conformational epitope showed minimal effector function. Citation Format: Xiaotao Jiang, Leidy D. Caraballo G., Huajun Zhang, Xiangyang Chi, Yibing Peng, Aiwu R. He, Yanxia Shao, Lun Cai, Yukai He. Development of novel chimeric antigen receptor T cells for immunotherapy of hepatocellular carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr B62.