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Purpose: One of the current challenges facing cancer gene therapy is the tumour-specific targeting of therapeutic genes. Effective targeting in gene therapy requires accurate spatial and temporal control of gene expression. To develop a sufficient and accurate tumour-targeting method for cancer gene therapy, we have investigated the use of hyperthermia to control the expression of a transgene under the control of the human telomerase reverse transcriptase (hTERT) promoter and eight heat shock elements (8HSEs).Materials and methods: Luciferase reporters were constructed by inserting eight HSEs and the hTERT promoter (8HSEs-hTERTp) upstream of the pGL4.20 vector luciferase gene. The luciferase activity of the hTERT promoter and 8HSEs-hTERT promoter were then compared in the presence and absence of heat. The differences in luciferase activity were analysed using dual luciferase assays in SW480 (high hTERT expression), MKN28 and MRC-5 cells (low hTERT expression). The luciferase activity of the Hsp70B promoter was also compared to the 8HSEs-hTERT promoter in the above listed cell lines. Lentiviral vector and heat-induced expression of EGFP expression under the control of the 8HSEs-hTERT promoter in cultured cells and mouse tumour xenografts was measured by reverse transcription polymerase (RT-PCR), Western blot and immunofluorescence assays.Results: hTERT promoter activity was higher in SW480 cells than in MKN28 or MRC-5 cells. At 43 °C, the luciferase activity of the 8HSEs-hTERT promoter was significantly increased in SW480 cells, but not in MKN28 or MRC-5 cells. Importantly, the differences in luciferase activity were much more obvious in both high (SW480) and low (MKN28 and MRC-5) hTERT expressing cells when the activity of the 8HSEs-hTERT promoter was compared to the Hsp70B promoter. Moreover, under the control of 8HSEs-hTERT promoterin vitroandin vivo, EGFP expression was obviously increased by heat treatment in SW480 cells but not in MKN28 or MRC-5 cells, nor was expression increased under normal temperature conditions.Conclusions: The hTERT promoter is a potentially powerful tumour-specific promoter and gene therapy tool for cancer treatment. Incorporating heat-inducible therapeutic elements (8HSEs) into the hTERT promoter may enhance the efficiency and specificity of cancer targeting gene therapy under hyperthermic clinical conditions. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a common malignant tumor, posing a great threat to human's health and life. Previous studies have suggested aberrant expression of long non-coding RNAs (lncRNAs) in GC. This study elucidated the effects of lncRNA ACTA2-AS1 on the biological characteristics of GC. Gene expression in stomach adenocarcinoma (STAD) samples compared with normal tissues and the correlation between gene expression and prognosis of STAD patients were analyzed using bioinformatic tools. Gene expression at protein and mRNA levels in GC and normal cells was tested by western blotting and RT-qPCR. The subcellular localization of ACTA2-AS1 in AGS and HGC27 cells was identified by nuclear-cytoplasmic fractionation and FISH assay. EdU, CCK-8, flow cytometry analysis, TUNEL staining assays were conducted to evaluate the role of ACTA2-AS1 and ESRRB on GC cellular behaviors. The binding relationship among ACTA2-AS1, miR-6720-5p and ESRRB was verified by RNA pulldown, luciferase reporter assay and RIP assay. LncRNA ACTA2-AS1 was underexpressed in GC tissues and cell lines. ACTA2-AS1 elevation suppressed GC cell proliferation and induced apoptosis. Mechanistically, ACTA2-AS1 directly bound to miR-6720-5p and subsequently promoted the expression of target gene ESRRB in GC cells. Furthermore, ESRRB knockdown reversed the influence of ACTA2-AS1 overexpression on GC proliferation and apoptosis. ACTA2-AS1 plays an antioncogenic role in GC via binding with miR-6720-5p to regulate ESRRB expression. [ABSTRACT FROM AUTHOR]

Objective: Fangcang shelter hospital is a form of large temporary hospital developed in China to tackle public health events. Through the case study and analysis of managing a nursing unit in a huge Fangcang shelter hospital transformed from the National Exhibition and Convention Center during the Omicron wave in Shanghai, China between April 9, 2022 and May 24, 2022, this paper aimed to highlight critical implications of public health nurses in health emergencies. Design: A case study was conducted using data collected from a nursing unit with 570 beds. The five characteristics of management were organized as follows: human resource management, establishment and optimization of the core workflow, safety management of high‐risk patients, the grid cooperation mechanism with patient volunteers, as well as humanistic nursing. Results: Analysis of the data of the nursing unit indicated close team cooperation, efficient and orderly process scheduling, good outcomes of patients, and the indispensable role of volunteers. Conclusion: Practice indicated that nursing unit management in a large Fangcang shelter hospital is important to ensure medical order and efficiency. This practical experience can provide valuable reference and data to support for the nursing management of large‐scale public health events, such as infectious disease epidemics. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) and mood disorders share pathophysiological commonalities in the central nervous system. The purpose of this study was to investigate the alterations in amygdala-based emotional processing circuits in T2DM patients with depressive mood using resting-state functional magnetic resonance imaging (rs-fMRI).Methods: T2DM patients with depressive mood (n = 25), T2DM patients without depressive mood (n = 28) and matched healthy controls (n = 25) underwent neuropsychological testing and rs-fMRI scanning. A seed-based correlation analysis was conducted to reveal the altered functional connectivity (FC) of the amygdala. The bilateral amygdala FC was compared among the three groups. Pearson correlation analyses were performed in a voxel-wise manner to investigate the relationship between amygdala FC and the clinical characteristics.Results: The depressed T2DM patients exhibited the worst performance on the neuropsychological tests among the three groups. Compared to the non-depressed T2DM patients, the depressed T2DM patients showed decreased amygdala FC in the cingulate cortex, inferior frontal gyrus, fusiform gyrus, and precentral gyrus. Moreover, the amygdala FC in the cingulate cortex was associated with the Self-Rating Depression Scale (SDS) score in the T2DM patients.Limitations: Cross-sectional design.Conclusions: The current study revealed the cognitive changes and alterations in the amygdala-cingulate functional disconnections in T2DM patients with depressive mood, which will advance the understanding of the neural mechanisms underlying depression in T2DM patients. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to investigate the effect of adding exenatide to continuous subcutaneous insulin infusion (CSII) therapy on the precise insulin doses required by type 2 diabetic patients to maintain glycemic control. Methods: This was a single-center, randomized, controlled, open-label trial. Uncontrolled T2D patients were recruited between March 2010 and November 2011 at Nanjing First Hospital, China. Subjects were randomly assigned (1:1) to either an exenatide add-on to CSII group or a CSII therapy only (i.e., control) group ( n = 18, respectively) for 5 weeks. Patients were subjected to 3 days of continuous glucose monitoring (CGM) during the screening period and after therapy. The precise insulin doses, the times taken by the patients to achieve euglycemic control, and the mean amplitude of glycemic excursion (MAGE) at the endpoint were compared between the two groups. The primary endpoint was precise insulin dose differences between groups from baseline to the endpoint. Results: A total of 36 subjects were admitted as inpatients. Patients in the exenatide add-on therapy group needed less insulin titration time to achieve glycemic control (3.67 ± 1.33 vs. 4.78 ± 1.00 days, P = 0.028) and significantly lower bolus insulin doses than the control group at the endpoint (total bolus, 0.13 ± 0.03 vs. 0.17 ± 0.04 U/kg, P = 0.02, breakfast bolus, 0.05 ± 0.01 vs. 0.06 ± 0.01 U/kg, P = 0.01, lunch bolus, 0.04 ± 0.01 vs. 0.06 ± 0.01 U/kg, P = 0.01, dinner bolus, 0.04 ± 0.01 vs. 0.05 ± 0.01 U/kg, P = 0.01, respectively). Moreover, the CGM data showed that patients in the exenatide add-on therapy group exhibited a significant reduction in MAGE as compared to the control group (2.96 ± 1.14 vs. 4.21 ± 1.39 mmol/L, P = 0.012). Conclusion: Our data suggest that adding exenatide therapy to CSII therapy leads to an improvement in glycemic excursions and the use of smaller bolus insulin doses. Trial Registration: Chinese Clinical Trial Registry identifier, ChiCTR-PPR-15007045. [ABSTRACT FROM AUTHOR]