Acquired treatment resistance is an important cause of death in prostate cancer, and this study aimed to explore the mechanisms of chemotherapy resistance in prostate cancer. We employed castration-resistant prostate cancer (CRPC), neuroendocrine prostate cancer (NEPC), and chemotherapy-resistant prostate cancer datasets to screen for potential target genes. The Cancer Genome Atlas (TCGA) was used to detect the correlation between the target genes and prognosis and clinical characteristics. Nei endonuclease VIII-like 3 (NEIL3) knockdown cell lines were constructed with RNA interference. Prostate cancer cells were treated with enzalutamide for the androgen deprivation therapy (ADT) model, and with docetaxel and cisplatin for the chemotherapy model. Apoptosis and the cell cycle were examined using flow cytometry. RNA sequencing and western blotting were performed in the knockdown Duke University 145 (DU145) cell line to explore the possible mechanisms. The TCGA dataset demonstrated that high NEIL3 was associated with a high T stage and Gleason score, and indicated a possibility of lymph node metastasis, but a good prognosis. The cell therapy models showed that the loss of NEIL3 could promote the chemotherapy resistance (but not ADT resistance) of prostate cancer (PCa). Flow cytometry revealed that the loss of NEIL3 in PCa could inhibit cell apoptosis and cell cycle arrest under cisplatin treatment. RNA sequencing showed that the knockdown of NEIL3 changes the expression of neuroendocrine-related genes. Further western blotting revealed that the loss of NEIL3 could significantly promote the phosphorylation of ATR serine/threonine kinase (ATR) and ATM serine/threonine kinase (ATM) under chemotherapy, thus initiating downstream pathways related to DNA repair. In summary, the loss of NEIL3 promotes chemotherapy resistance in prostate cancer, and NEIL3 may serve as a diagnostic marker for chemotherapy-resistant patients.

Aims and objectives:To investigate the relationship between illness uncertainty, selfperceived burden and quality of life and explore the mediating role of self-perceived burden between illness uncertainty and quality of life in patients with chronic myeloid leukaemia.Background: Patients with chronic myeloid leukaemia need long-term, potentially lifelong therapy to control the disease, which affects their quality of life. There is a need for exploring potentially changeable factors to develop interventions. Little is known about the effects of illness uncertainty and self-perceived burden on quality of life in this population. Design:A cross-sectional study. Methods: A convenience sample of 248 patients with chronic myeloid leukaemia was recruited from four university hospitals from February to August 2020. Participants were assessed with the Mishel Uncertainty in Illness Scale, Self-Perceived Burden Scale, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. The STROBE checklist was used to report the results.Results: Illness uncertainty and self-perceived burden were negatively associated with quality of life in patients with chronic myeloid leukaemia. Self-perceived burden partially mediated the relationship between illness uncertainty and quality of life. The indirect effect was −0.101, accounting for 22.9% of the total effect. Conclusion:The findings revealed the relationship between illness uncertainty, selfperceived burden and quality of life in patients with chronic myeloid leukaemia. Selfperceived burden exerted a mediating role between illness uncertainty and quality of life in this population. Relevance to clinical practice:This study alerts healthcare providers to pay attention to patients' illness uncertainty and self-perceived burden, which can contribute to develop effective interventions to improve the quality of life among patients with chronic myeloid leukaemia in the clinical practice.

Forsythiaside A, a phenylethanoid glycoside monomer extracted from Forsythia suspensa, shows anti-inflammatory, anti-infective, anti-oxidative, and antiviral pharmacological effects. The precise mechanism underlying the antiviral action of forsythiaside A is not completely clear. Therefore, in this study, we aimed to determine whether the anti-influenza action of forsythiaside A occurs via the retinoic acid-inducible gene-I–like receptors (RLRs) signaling pathway in the lung immune cells. Forsythiaside A was used to treat C57BL/6J mice and MAVS−/− mice infected with mouse-adapted influenza A virus FM1 (H1N1, A/FM1/1/47 strain), and the physical parameters (body weight and lung index) and the expression of key factors in the RLRs/NF-κB signaling pathway were evaluated. At the same time, the level of virus replication and the ratio of Th1/Th2 and Th17/Treg of T cell subsets were measured. Compared with the untreated group, the weight loss in the forsythiaside A group in the C57BL/6J mice decreased, and the histopathological sections showed less inflammatory damage after the infection with the influenza A virus FM1 strain. The gene and protein expression of retinoic acid-inducible gene-I (RIG-I), MAVS, and NF-κB were significantly decreased in the forsythiaside A group. Flow cytometry showed that Th1/Th2 and Th17/Treg differentiated into Th2 cells and Treg cells, respectively, after treatment with forsythiaside A. In conclusion, forsythiaside A reduces the inflammatory response caused by influenza A virus FM1 strain in mouse lungs by affecting the RLRs signaling pathway in the mouse lung immune cells.

Background: Previous studies indicated that the (neo)adjuvant chemotherapy for breast cancer can cause significant dyslipidemia in patients, but how long this abnormality can persist is unclear so far. The purpose of this study is to investigate whether (neo)adjuvant chemotherapy has a long-term effect on blood lipids in breast cancer patients. Methods: A total of 159 newly diagnosed female breast cancer patients receiving the (neo) adjuvant chemotherapy subsequently and 159 female healthy controls were enrolled into the observational study. All participants' blood lipid profiles which included TC, TG, HDL-C, and LDL-C before and at the end of the 1st and 12th month after chemotherapy were retrieved from the electronic medical record system. The blood lipid profiles and the percentage of dyslipidemia before and after chemotherapy in breast cancer patients and controls were compared. Results: Compared with the baseline before chemotherapy, TC, LDL-C, and TG increased significantly at the end of the 1st month after chemotherapy, but only the abnormal increase in TG (2.98±0.71 mmol/L vs 2.82±0.63 mmol/L, P<0.05) and LDL-C (1.82±0.42 mmol/L vs 1.59±0.42 mmol/L, P<0.05) continued until the 12th month after chemotherapy. Levels of HDL-C in breast cancer patients and all the blood lipid parameters in controls remained stable during the observation period. The percentage of dyslipidemia in breast cancer patients rose from 41.5% at baseline to 54.1% at the 12th month after chemotherapy. Subgroup analysis demonstrated that the increase in dyslipidemia percentage was more pronounced in patients with low body mass index and aged over 50 years. Conclusion: The (neo)adjuvant chemotherapy used for treating breast cancers can cause significant abnormalities in blood lipid profiles, and the abnormal increase in LDL-C and TG can last at least 12 months after chemotherapy, which indicates long-term management of blood lipid is necessary for those patients.

Introduction: LncRNA mortal obligate RNA transcript (MORT) is downregulated in different types of cancer, indicating its involvement in cancer biology. Methods: In this study, MORT and miRNA-16 were both downregulated in plasma of mantle cell lymphoma (MCL) patients than that in the controls. The low levels of MORT and miRNA-16 were correlated with poor survival of MCL patients. The expression of MORT and miRNA-16 was positively correlated only in MCL patients. Results: Overexpression of MORT and miRNA-16 suppressed cell proliferation but promoted cancer cell apoptosis, while miRNA-16 inhibitor reduced the effects of MORT overexpression. Overexpression of MORT led to upregulated expression of miRNA-16, while overexpression of miRNA-16 had no effect on the expression of MORT. Conclusion: Therefore, MORT may inhibit cancer cell proliferation and promote apoptosis in mantle cell lymphoma by upregulating miRNA-16.