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Guan-Nan He, Na-Ren Bao, Shuang Wang, Man Xi, Tian-Hao Zhang, Feng-Shou Chen Department of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang, 110001, Liaoning, People’s Republic of ChinaCorrespondence: Feng-Shou ChenDepartment of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang, 110001, Liaoning, People’s Republic of ChinaEmail shouyongpang4540@163.comBackground: Liver cancer ranks the top four malignant cancer type worldwide, which needs effective and safe treatment. Ferroptosis is a novel form of regulated cell death driven by iron-dependent lipid peroxidation and has been regarded as a promising therapeutic target for cancers. In this work, we aimed to study the effects of anesthetic ketamine on proliferation and ferroptosis of liver cancer.Methods: Cell viability and proliferation were detected by cell counting kit 8 (CCK-8), colony formation, and 5-ethynyl-2′-deoxyuridine (EdU) assay. Ferroptosis was determined by levels of Fe2+, lipid reactive oxygen species (ROS), and malondialdehyde (MDA). RNA levels of lncPVT1, miR-214-3p, and glutathione peroxidase 4 (GPX4) were checked by real-time PCR assay. Clinical liver tumor samples were collected to detect the levels of long noncoding RNA lncPVT1, miR-214-3p, and GPX4, and their correlation was evaluated by Pearson comparison test. Luciferase reporter gene assay and RNA pulldown were conducted to determine the binding between lncPVT1, miR-214-3p, and GPX4 3ʹUTR.Results: Ketamine significantly suppressed viability and proliferation of liver cancer cells both in vitro and in vivo, as well as stimulated ferroptosis, along with decreased expression of lncPVT1 and GPX4. LncPVT1 directly interacted with miR-214-3p to impede its role as a sponge of GPX4. Depletion of lncPVT1 accelerated the ferroptosis of live cancer cells, whereas miR-214-3p inhibition and GPX4 overexpression reversed this effect. Ketamine-induced cell growth suppression and ferroptosis were also suppressed by miR-214-3p inhibition and GPX4 overexpression.Conclusion: In this work, we determined that ketamine suppressed viability of liver cancer cells and induced ferroptosis and identified the possible regulatory mechanism of lncPVT1/miR-214-3p/GPX4 axis.Keywords: liver cancer, ketamine, lncPVT1, miR-214-3p, GPX4

Jing Ren,1 Quanlei Li,2 Tianhua Zhang,3 Xiaomei Li,4 Shaoru Zhang,1,4 Jiaojiao Wright,2 Haini Liu,4 Zhongqiu Hua4 1School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, Shanxi, China; 2School of Nursing, Johns Hopkins University, Baltimore, MD, USA; 3Shaanxi Provincial Institute for Tuberculosis Control and Prevention, Xi’an, Shanxi, China; 4School of Nursing, Health Science Center, Xi’ an Jiaotong University, Xi’an, Shanxi, China Purpose: Adherence to treatment is cited as a key challenge in fighting tuberculosis (TB). Treatment of TB requires patients to actively engage in their care. The purpose of this study was to explore the perceptions of patients with TB regarding their engagement in health care.Patients and methods: The study was conducted in three medical wards in one hospital. Purposive sampling was used to recruit participants. Semi-structured, audiotaped interviews were conducted and analyzed using thematic analysis.Results: Twenty-three patients participated in the study. Four major themes emerged: 1) devaluing engagement; 2) interacting with health care providers (HCPs); 3) facing inability; and 4) seeking external support.Conclusion: The patients’ perceptions of their engagement in health care were generally negative. Paying attention to the preferences and needs of patients and making decisions accordingly are effective strategies for promoting patient engagement. Moreover, HCPs should be aware of their crucial role in helping patients make sense of what engagement is and how to engage. In the process of engagement, providers should establish effective interactions with patients and cooperate with family and peers. Keywords: tuberculosis, patient engagement, qualitative study, treatment adherence

TianHong Zhang,1 HuiJun Li,2,3 Kristen A Woodberry,3 Larry J Seidman,3 Annabelle Chow,4 ZePing Xiao,1 JiJun Wang1 1Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Psychology, Florida A&M University, Tallahassee, FL, USA; 3Department of Psychiatry, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA; 4Department of Psychological Medicine, Changi General Hospital, Singapore Abstract: Clinical high risk of psychosis is defined as the period in which the first signs of psychotic symptoms begin to appear. During this period, there is an increased probability of developing frank psychosis. It is crucial to investigate the interaction between psychotic symptoms and the individual’s personality and life experiences in order to effectively prevent, or delay the development of psychosis. This paper presents case reports of three Chinese female subjects with attenuated positive symptoms, attending their initial outpatient assessment in a mental health service, and their longitudinal clinical outcomes. Information regarding each subject’s symptoms and life stressors was collected at 2-month intervals over a 6-month period. The assessments indicated that these women were suffering from the recent onset of symptoms in different ways. However, all three hid their symptoms from others in their school or workplace, and experienced a decline in performance related to their social roles and in their daily functioning. They were often excluded from the social groups to which they had previously belonged. A decline in social activities may be a risk factor in the development of psychosis and a mediator of functional sequelae in psychosis. Effective treatment strategies may include those that teach individuals to gain insights related to their symptoms and a service that provides a context in which individuals can discuss their psychotic symptoms. Keywords: prodromal psychosis, ultra high risk, follow-up, functional sequelae, transition

Abstract Background Hyperactivation of the Ras signaling pathway is a driver of many cancers, and RAS pathway activation can predict response to targeted therapies. Therefore, optimal methods for measuring Ras pathway activation are critical. The main focus of our work was to develop a gene expression signature that is predictive of RAS pathway dependence. Methods We used the coherent expression of RAS pathway-related genes across multiple datasets to derive a RAS pathway gene expression signature and generate RAS pathway activation scores in pre-clinical cancer models and human tumors. We then related this signature to KRAS mutation status and drug response data in pre-clinical and clinical datasets. Results The RAS signature score is predictive of KRAS mutation status in lung tumors and cell lines with high (> 90%) sensitivity but relatively low (50%) specificity due to samples that have apparent RAS pathway activation in the absence of a KRAS mutation. In lung and breast cancer cell line panels, the RAS pathway signature score correlates with pMEK and pERK expression, and predicts resistance to AKT inhibition and sensitivity to MEK inhibition within both KRAS mutant and KRAS wild-type groups. The RAS pathway signature is upregulated in breast cancer cell lines that have acquired resistance to AKT inhibition, and is downregulated by inhibition of MEK. In lung cancer cell lines knockdown of KRAS using siRNA demonstrates that the RAS pathway signature is a better measure of dependence on RAS compared to KRAS mutation status. In human tumors, the RAS pathway signature is elevated in ER negative breast tumors and lung adenocarcinomas, and predicts resistance to cetuximab in metastatic colorectal cancer. Conclusions These data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical utility in lung and breast tumors.

Abstract Background Targeted transport of messenger RNA and local protein synthesis near the synapse are important for synaptic plasticity. In order to gain an overview of the composition of the dendritic mRNA pool, we dissected out stratum radiatum (dendritic lamina) from rat hippocampal CA1 region and compared its mRNA content with that of stratum pyramidale (cell body layer) using a set of cDNA microarrays. RNAs that have over-representation in the dendritic fraction were annotated and sorted into function groups. Results We have identified 154 dendritic mRNA candidates, which can be arranged into the categories of receptors and channels, signaling molecules, cytoskeleton and adhesion molecules, and factors that are involved in membrane trafficking, in protein synthesis, in posttranslational protein modification, and in protein degradation. Previously known dendritic mRNAs such as MAP2, calmodulin, and G protein gamma subunit were identified from our screening, as were mRNAs that encode proteins known to be important for synaptic plasticity and memory, such as spinophilin, Pumilio, eEF1A, and MHC class I molecules. Furthermore, mRNAs coding for ribosomal proteins were also found in dendrites. Conclusion Our results suggest that neurons transport a variety of mRNAs to dendrites, not only those directly involved in modulating synaptic plasticity, but also others that play more common roles in cellular metabolism.