Transcriptomic analysis and experiments revealed that remimazolam promotes proliferation and G1/S transition in HCT8 cells.

Background: Remimazolam is a new ultrashort-acting benzodiazepine for sedation and anesthesia. The effects of remimazolam and the mechanism by which it functions in cancer cells have not been determined. This research aimed to explore the mechanism of remimazolam action in colon cancer treatment, using bioinformatics analysis and in vitro experiments. Methods: Cell cycle progression, colony formation, self-renewal capacity, and apoptosis detection were performed in HCT8 cells treated with or without remimazolam. Transcriptome sequencing, Gene Ontology, Kyoto Encyclopedia of Genes and Genome, Protein-Protein Interaction, Gene Set Enrichment Analysis, Western blotting, and qPCR were performed to investigate the mechanism of action of remimazolam in HCT8 colon cancer cells. Results: Remimazolam promoted proliferation and cell-cycle progression of HCT8 cells. After remimazolam treatment, a total of 1,096 differentially expressed genes (DEGs) were identified: 673 genes were downregulated, and 423 genes were upregulated. The DEGs were enriched mainly in "DNA replication", "cell cycle", and "G1/S transition" related pathways. There were 15 DEGs verified by qPCR, and representative biomarkers were detected by Western Bloting. The remimazolam-mediated promotion of cell proliferation and cell cycle was reversed by G1T28, a CDK4/6 inhibitor. Conclusion: Remimazolam promoted cell-cycle progression and proliferation in HCT8 colon cancer cells, indicating that the long-term use of remimazolam has potential adverse effects in the anesthesia of patients with colon cancer.

Establishment and Validation of a Transdermal Drug Delivery System for the Anti-Depressant Drug Citalopram Hydrobromide.

To enhance the bioavailability and antihypertensive effect of the anti-depressant drug citalopram hydrobromide (CTH) we developed a sustained-release transdermal delivery system containing CTH. A transdermal diffusion meter was first used to determine the optimal formulation of the CTH transdermal drug delivery system (TDDS). Then, based on the determined formulation, a sustained-release patch was prepared; its physical characteristics, including quality, stickiness, and appearance, were evaluated, and its pharmacokinetics and irritation to the skin were evaluated by applying it to rabbits and rats. The optimal formulation of the CTH TDDS was 49.2% hydroxypropyl methyl cellulose K100M, 32.8% polyvinylpyrrolidone K30, 16% oleic acid-azone, and 2% polyacrylic acid resin II. The system continuously released an effective dose of CTH for 24 h and significantly enhanced its bioavailability, with a higher area under the curve, good stability, and no skin irritation. The developed CTH TDDS possessed a sustained-release effect and good characteristics and pharmacokinetics; therefore, it has the potential for clinical application as an antidepressant.

Propofol inhibits colon cancer cell stemness and epithelial-mesenchymal transition by regulating SIRT1, Wnt/ß-catenin and PI3K/AKT/mTOR signaling pathways.

BACKGROUND: Propofol is a common sedative-hypnotic drug used for general anesthesia. Recent studies have drawn attention to the antitumor effects of propofol, but the potential mechanism by which propofol suppresses colon cancer stemness and epithelial-mesenchymal transition (EMT) has not been fully elucidated. METHODS: For the in vitro experiments, we used propofol to treat LOVO and SW480 cells and Cell Counting Kit-8 (CCK-8) to detect proliferation. Self-renewal capacity, cell invasion and migration, flow cytometry analysis, qPCR and Western blotting were performed to detect the suppression of propofol to colon cancer cells and the underlying mechanism. Tumorigenicity and immunohistochemistry experiments were performed to confirm the role of propofol in vivo. RESULT: We observed that propofol could suppressed stem cell-like characteristics and EMT-related behaviors, including self-renewal capacity, cell invasion and migration in colon cancer cells, and even suppressed tumorigenicity in vivo. Furthermore, investigations of the underlying mechanism revealed that propofol treatment downregulated SIRT1. SIRT1 overexpression or knockdown affected the stemness and EMT of colon cancer cells. Additionally, propofol reversed stemness and EMT in cells with overexpressing SIRT1 and subsequently inhibited the Wnt/ß-catenin and PI3K/AKT/mTOR signaling pathways. Wnt/ß-catenin pathway inhibitor and PI3K/AKT/mTOR pathway inhibitor blocked the propofol-induced reduction of sphere-formation and cell invasion-migration. CONCLUSION: Propofol inhibits LOVO and SW480 cell stemness and EMT by regulating SIRT1 and the Wnt/ß-catenin and PI3K/AKT/mTOR signaling pathways. Our findings indicate that propofol inhibits SIRT1 in cancer and is advantageous in colon cancer surgical treatment of patients with high SIRT1 expression.

Towards a global partnership model in interprofessional education for cross-sector problem-solving.

OBJECTIVES: A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. METHODS: This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students' data. RESULTS: We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest-posttest differences in students' readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students' social interaction anxiety after the IPE simulation. CONCLUSIONS: The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education.

Sevoflurane upregulates neuron death process-related Ddit4 expression by NMDAR in the hippocampus.

Postoperative cognitive dysfunction (POCD) is a serious and common complication induced by anesthesia and surgery. Neuronal apoptosis induced by general anesthetic neurotoxicity is a high-risk factor. However, a comprehensive analysis of general anesthesia-regulated gene expression patterns and further research on molecular mechanisms are lacking. Here, we performed bioinformatics analysis of gene expression in the hippocampus of aged rats that received sevoflurane anesthesia in GSE139220 from the GEO database, found a total of 226 differentially expressed genes (DEGs) and investigated hub genes according to the number of biological processes in which the genes were enriched and performed screening by 12 algorithms with cytoHubba in Cytoscape. Among the screened hub genes, Agt, Cdkn1a, Ddit4, and Rhob are related to the neuronal death process. We further confirmed that these genes, especially Ddit4, were upregulated in the hippocampus of aged mice that received sevoflurane anesthesia. NMDAR, the core target receptor of sevoflurane, rather than GABAAR, mediates the sevoflurane regulation of DDIT4 expression. Our study screened sevoflurane-regulated DEGs and focused on the neuronal death process to reveal DDIT4 as a potential target mediated by NMDAR, which may provide a new target for the treatment of sevoflurane neurotoxicity.

Students' interaction anxiety and social phobia in interprofessional education in Hong Kong: mapping a new research direction.

BACKGROUND: Interprofessional education (IPE) has been promoted as a breakthrough in healthcare because of the impact when professionals work as a team. However, despite its inception dating back to the 1960s, its science has taken a long time to advance. There is a need to theorize IPE to cultivate creative insights for a nuanced understanding of IPE. This study aims to propose a research agenda on social interaction by understanding the measurement scales used and guiding researchers to contribute to the discussion of social processes in IPE. METHOD: This quantitative research was undertaken in a cross-institutional IPE involving 925 healthcare students (Medicine, Nursing, Social Work, Chinese Medicine, Pharmacy, Speech Language Pathology, Clinical Psychology, Food and Nutritional Science and Physiotherapy) from two institutions in Hong Kong. Participants completed the Social Interaction Anxiety Scale (SIAS-6) and Social Phobia Scale (SPS-6). We applied a construct validation approach: within-network and between-network validation. We performed confirmatory factors analysis, t-test, analysis of variance and regression analysis. RESULTS: CFA results indicated that current data fit the a priori model providing support to within-network validity [RMSEA=.08, NFI=.959, CFI=.965, IFI=.965, TLI=.955]. The criteria for acceptable fit were met. The scales were invariant between genders, across year levels and disciplines. Results indicated that social interaction anxiety and social phobia negatively predicted behavioural engagement (F = 25.093, p<.001, R2=.065) and positively predicted behavioural disaffection (F = 22.169, p<.001, R2=.057) to IPE, suggesting between-network validity. CONCLUSIONS: Our data provided support for the validity of the scales when used among healthcare students in Hong Kong. SIAS-6 and SPS-6 have sound psychometric properties based on students' data in Hong Kong. We identified quantitative, qualitative and mixed methods research designs to guide researchers in getting involved in the discussion of students' social interactions in IPE.Key MessagesThe Social Anxiety Scale (SIAS-6) and Social Phobia Scale (SPS-6) scales have sound psychometric properties based on the large-scale healthcare students' data in IPE in Hong Kong.Social interaction anxiety and social phobia negatively predicted students' behavioural engagement with IPE and positively predicted behavioural disaffection. The scales are invariant in terms of gender, year level and discipline.Quantitative, qualitative and mixed methods studies are proposed to aid researchers to contribute in healthcare education literature using the SIAS-6 and SPS-6.

Autonomous motivation predicts students' engagement and disaffection in interprofessional education: Scale adaptation and application.

OBJECTIVES: Despite the popularity of interprofessional education, the empirical and theoretical development of its scholarship and science is just emerging. This may be caused in part by the non-availability of measures that can be used by researchers in this field. This study aimed to contribute to the psychological theorizing of interprofessional education by uncovering the psychometric properties of Perceived Locus of Causality adapted to Interprofessional Education (PLOC-IPE) in healthcare education and provide a comprehensive guide on how this can be used to advance the IPE research agenda. METHODS: Confirmatory factor analysis (quantitative design) was used to examine the acceptability of psychometric properties of PLOC-IPE. Data were collected through questionnaires administered at two different time points. The participants consisted of 345 students from Chinese Medicine, Clinical Psychology, Medicine, Nursing, Pharmacy, and Social Work from a university in Hong Kong. RESULTS: Based on confirmatory factor analysis, results of within-network construct validity showed good psychometric properties of PLOC-IPE while between-network validity indicated that the scale can predict IPE-related outcomes. Students' intrinsic motivation in IPE positively predicted emotional engagement and negatively predicted emotional disaffection, demonstrating the applicability of the newly validated PLOC-IPE. Amotivation was a negative predictor of emotional engagement and a positive predictor of emotional disaffection. CONCLUSIONS: Findings support the acceptability of PLOC when adapted to IPE. PLOC-IPE obtained acceptable psychometric properties as a measure of students' academic motivation in IPE. It is an adapted scale that can be used to understand self-determined motivation in the context of IPE in health and social care education. A guide on how PLOC-IPE can be a means by which researchers can contribute to the advancement of scholarship of IPE was provided.

Preoperative smoking history is associated with decreased risk of early postoperative cognitive dysfunction in patients of advanced age after noncardiac surgery: a prospective observational cohort study.

OBJECTIVE: Prevention of postoperative cognitive dysfunction (POCD) in patients of advanced age remains unclear. Studies have shown that the cholinergic anti-inflammatory pathway contributes to a decreased risk of POCD and that nicotine stimulates the cholinergic anti-inflammatory pathway. We investigated whether patients of advanced age with a preoperative smoking history have a decreased risk of POCD. METHODS: In total, 382 patients (190 smokers, 192 nonsmokers) aged ≥60 years who underwent major noncardiac surgery were enrolled. Cognitive function was assessed, and multivariate logistic regression analyses were performed to identify risk factors. RESULTS: On postoperative days 5 and 7, 111 (29.05%) and 90 (23.56%) patients exhibited POCD, respectively. A preoperative smoking history was significantly correlated with a decreased risk of POCD. A high serum tumor necrosis factor-α (TNF-α) level on the operative day was significantly associated with an increased risk of POCD. Early POCD was significantly associated with the sufentanil dosage, age, and education level. The hospital stay in patients with and without POCD was 10.54 ± 2.03 and 8.33 ± 1.58 days, respectively. CONCLUSION: A preoperative smoking history was associated with a decreased risk of early POCD, and a high serum TNF-α level was significantly associated with an increased risk of POCD.