Modulation of epithelial-mesenchymal transition by gemcitabine: Targeting ionizing radiation-induced cellular senescence in lung cancer cell.

Ionizing radiation, a standard therapeutic approach for lung cancer, often leads to cellular senescence and the induction of epithelial-mesenchymal transition (EMT), posing significant challenges in treatment efficacy and cancer progression. Overcoming these obstacles is crucial for enhancing therapeutic outcomes in lung cancer management. This study investigates the effects of ionizing radiation and gemcitabine on lung cancer cells, with a focus on induced senescence, EMT, and apoptosis. Human-derived A549, PC-9, and mouse-derived Lewis lung carcinoma cells exposed to 10 Gy X-ray irradiation exhibited senescence, as indicated by morphological changes, ß-galactosidase staining, and cell cycle arrest through the p53-p21 pathway. Ionizing radiation also promoted EMT via TGFß/SMAD signaling, evidenced by increased TGFß1 levels, altered EMT marker expressions, and enhanced cell migration. Gemcitabine, a first-line lung cancer treatment, was shown to enhance apoptosis in senescent cells caused by radiation. It inhibited cell proliferation, induced mitochondrial damage, and triggered caspase-mediated apoptosis, thus mitigating EMT in vitro. Furthermore, in vivo studies using a lung cancer mouse model revealed that gemcitabine, combined with radiation, significantly reduced tumor volume and weight, extended survival, and suppressed malignancy indices in irradiated tumors. Collectively, these findings demonstrate that gemcitabine enhances the therapeutic efficacy against radiation-resistant lung cancer cells, both by inducing apoptosis in senescent cells and inhibiting EMT, offering potential improvements in lung cancer treatment strategies.

Efficacy of Intravitreal Injections Anti-Vascular Endothelial Growth Factor Treatment for Radiation Retinopathy: A Systematic Review and Meta-analysis.

PURPOSE: This study aims to appraise the therapeutic effectiveness of intravitreal injections anti-vascular endothelial growth factor (anti-VEGF) vs alternative therapies in managing radiation retinopathy (RR). DESIGN: Systematic review and meta-analysis. METHODS: We obtained comprehensive data retrieval using PubMed, Embase, Web of Science, Scopus, and the Cochrane Library from their inception until December 15, 2023. This review included randomized controlled trials (RCTs) and nonrandomized studies (NRSs) reporting on best-corrected visual acuity (BCVA) among RR patients treated with intravitreal anti-VEGF. Study selection and data extraction were meticulously performed by 2 independent reviewers. The Cochrane Risk of Bias Tool 2.0 (RoB 2.0) and Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) scales were utilized for bias risk assessment. Quantification of heterogeneity was executed using Q, H, and I2 statistics. The primary endpoint was the BCVA at the final observation point of each study. Secondary endpoints included central retinal thickness (CRT), foveal avascular zone (FAZ) area, and capillary density (CD) at the level of superficial capillary plexus. Subgroup analyses were undertaken to explore potential heterogeneity sources possibly due to treatment duration and study design. Sensitivity analyses were conducted to ascertain result stability. RESULTS: This analysis incorporated 7 studies (including 3 RCTs) encompassing 922 patients afflicted with RR. Relative to other treatment modalities, intravitreal anti-VEGF therapy was associated with a statistically significant mean decrease in BCVA of -0.34 logMAR (95% CI, -0.39 to -0.30 logMAR; I2 = 87.70%; P < .001), and a substantial reduction in CRT of -34.65 µm (95% CI, -50.70 to -18.60 µm; I2 = 30.40%; P < .001). Additionally, a reduction in the FAZ area by -0.69 mm² (95% CI, -0.91 to -0.46 mm², I2 = 0%; P < .001) was observed. A positive tendency was noted in CD at the superficial capillary plexus between anti-VEGF and other therapeutic interventions. CONCLUSIONS: Intravitreal anti-VEGF injections, in comparison to other treatments, demonstrate superior efficacy in enhancing BCVA and reducing CRT, thereby underscoring the potential of anti-VEGF in ameliorating radiation retinopathy outcomes. However, the conclusions are constrained by the incorporation of data from some NRSs and the small sample sizes.

Distributed finite-time bearing-based formation control for underactuated surface vessels with Levant differentiator.

In this paper, a distributed bearing-based formation control scheme with finite-time convergency is proposed for multiple underactuated surface vessels (USVs). By virtue of the guide point-based model transformation method, the dimension of underactuated tracking error dynamics can be reduced from three to two. This allows us to convert the actuator model to a fully form that matches dimension-reduced tracking error dynamics. Further, to reduce the computation complexity, a finite-time recruited filter is designed according to first-order Levant differentiator. At meanwhile, auxiliary error compensation signals are introduced to address unknowns stemming from filter process and system dynamics. Since merely relative-distances and inner bearings are utilized in the proposed bearing-based formation approaches, the proposed control scheme provides a feasible solution to achieve formation control under body-fixed frame. Finally, theoretical analysis and numerical simulations are presented to demonstrate the efficacy.

Clinical Pathway for Enhanced Recovery in the Management of Non-Variceal Upper Gastrointestinal Bleeding: A Randomized Controlled Trial.

Purpose: To explore the effects of the clinical pathway on the outcomes of patients with non-variceal upper gastrointestinal bleeding. Materials and Methods: Randomized controlled trial. The study was conducted in two medical centers in China from 1 June 2022 to 31 December 2022. Patients with a diagnosis of non-variceal upper gastrointestinal bleeding who provided written informed consent were consecutively assigned to the intervention group. The patients in the intervention group were treated using the clinical pathway, while the control group received routine care and follow-up. Time, cost, complications, and prognostic indicators were analyzed. Intentional-to-treat analysis and per-protocol analysis were used for data analysis. Results: A total of 114 eligible patients with non-variceal upper gastrointestinal bleeding were randomly divided into two groups and included in the intention-to-treat analysis. In addition, 106 patients were included in the per-protocol analysis. The median age of the 106 patients was 57 years (range, 18-92 years) and 83.0% were male. There were no significant differences between groups regarding the baseline characteristics. The intervention group demonstrated a statistically significantly shorter length of stay, lower hospital cost (ie, cost during hospitalization, cost in the emergency room, and cost in the ward), significantly fewer cases of complications, and a higher level of patient satisfaction when compared with the control group. There was no significant difference between the two groups in the rates of transfusion, repeat endoscopy, rebleeding readmission, and mortality. Conclusion: The implementation of the clinical pathway for patients with non-variceal upper gastrointestinal bleeding may help improve patient outcomes and satisfaction. Trial Registration Number: ChiCTR2200060316. Registration Link: https://www.chictr.org.cn/.

Retracted: Effects of Different Ratio of n-6/n-3 Polyunsaturated Fatty Acids on the PI3K/Akt Pathway in Rats With Reflux Esophagitis.

This publication has been retracted by the Editor due to non-original content and deficiencies in the conduct of the study. Reference: Jia-Yuan Zhuang, Zhi-Yao Chen, Tao Zhang, Du-Peng Tang, Xiao-Yin Jiang, Ze-Hao Zhuang. Effects of Different Ratio of n-6/n-3 Polyunsaturated Fatty Acids on the PI3K/Akt Pathway in Rats with Reflux Esophagitis. Med Sci Monit, 2017; 23: 542-547. DOI: 10.12659/MSM.898131.

The incidence of elder abuse under East Asian cultural background: A systematic review and meta-analysis.

OBJECTIVE: Elder abuse (EA) is a critical social, health, and economic issue worldwide. To date, there is limited information on EA in certain similar culture-specific subpopulations, especially in East Asia. This study aims to summarize EA incidence in East Asia through a systematic review and meta-analysis and identify its variations and heterogeneity in the incidence estimates. METHODS/DESIGN: The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses protocol. Systematic review registration number PROSPERO CRD42020197131. A systematic literature search was performed to identify relevant articles published before July 5th, 2020, from six electronic databases. Two reviewers screened for relevance of the studies against eligible criteria and assessed the bias of the included studies independently. A random-effect model was adopted to estimate the incidence of EA, followed by subgroup analyses and multi meta-regression. Sensitivity and publication bias tests were performed to verify the robustness of the meta-analysis by Stata version 15.1. RESULTS: Twelve eligible studies were included in the meta-analysis, which involved 79,395 subjects from 3 East Asian countries (China, Japan, and South Korea) ranging from 2004 to 2020. The overall incidence of EA was 78.33 per 1000 person-year (95% CI: 39.12-156.87) with high between-study variability (χ2  = 15,568, d.f. = 11, p<0.001; I2  = 99.9%). The sampling method, sample size, scope, instrument, data collection method, income classification, types of participants, and urbanity are all the sources of heterogeneity, which can explain nearly 100% of the variance between studies. CONCLUSIONS: The incidence of EA in this study is not as high as the global level. It may be furtherly underestimated in East Asia due to cultural norms. It is imperative to develop a culture-tailored EA assessment instrument to evaluate potential victims. Future studies should also identify more effective educational programs to raise the public's awareness and promote recognition ability.

Effects of blended versus offline case-centred learning on the academic performance and critical thinking ability of undergraduate nursing students: A cluster randomised controlled trial.

OBJECTIVE: This study aimed to compare the effect of blended and offline case-centred learning on medical nursing education for undergraduate nursing students. BACKGROUND: Technological advancements are rapidly changing nursing education in higher educational settings. Educational reform, especially regarding methods of teaching, has been the focus of nursing educators in recent years. DESIGN: The research was conducted between September 2018 and July 2019 in China. METHODS: Second-year undergraduate nursing students in two classes were enrolled for this study by cluster sampling. The study outcomes were academic performance and critical thinking ability, measured using the Critical Thinking Disposition Inventory-Chinese Version. RESULTS: Students in the experimental class showed significantly higher improvements in academic performance than those in the control class. Compared with the control class, the pre-post difference in competency in critical thinking self-confidence in the experimental class was significantly greater (p = 0.037). In the experimental class, there was a significant improvement over the baseline in the dimension of critical thinking self-confidence (p = 0.022). In the control class, there was a significant improvement over the baseline in the total score (p = 0.029) and two of the seven dimensions: truth-seeking (p = 0.016) and systematicity (p = 0.005). CONCLUSIONS: The use of blended case-centred learning showed promising results in improving students' academic performance. Both blended and offline case-centred learning were indicated to be effective educational approaches to improve the critical thinking ability of undergraduate nursing students and could be implemented for other nursing subjects in the future.

Reflections on Nursing Educational Advancement Within Diverse and Evolving National Cultural Contexts.

As the development of nursing education becomes increasingly internationalized, it is tempting to focus on universal aspects of the discipline rather than explicitly emphasizing the distinct national cultures and contexts within which our profession and its educational styles and approaches have evolved. Capitalizing on an opportunity for comparative critical reflection on the relevant political, economic and social histories that have underpinned the development of nursing education in China, Brazil and Canada - three countries united by shared values about equity and access to health services - we sought to deconstruct the manner in which these forces have shaped the national differences in the way we conceptualize and deliver nursing education. On this basis, we examined the implications for the advancement of nursing education within each national context, recognizing the fundamental relevance of indepth critical reflection for optimizing nursing's advocacy capacity within each of our national health care and policy systems.

Dexmedetomidine Mitigates Microglia-Mediated Neuroinflammation through Upregulation of Programmed Cell Death Protein 1 in a Rat Spinal Cord Injury Model.

Excessive neuroinflammation aggravates neurological damage after spinal cord injury (SCI). Controlling neuroinflammation might favor neuroregeneration and tissue repair. Dexmedetomidine is reported to inhibit post-SCI neuroinflammation in previous research. In the current study, to determine the mechanisms by which dexmedetomidine inhibits neuroinflammation, we tested the effect of dexmedetomidine hydrochloride on microglia in vitro and in a rat SCI model. We found that dexmedetomidine hydrochloride up-regulated programmed cell death protein 1 (PD-1), an immunoregulatory molecule, in activated microglia but not in resting microglia. In the presence of programmed death-ligand 1 (PD-L1), this enhanced PD-1 expression downregulated pro-inflammatory cytokine expression and upregulated anti-inflammatory cytokine expression in activated microglia. PD-L1/PD-1 engagement also induced microglia polarization toward the immunoregulatory M2 type. Moreover, dexmedetomidine hydrochloride promoted 5' adenosine monophosphate-activated protein kinase (AMPK) signaling in activated microglia. AMPK signaling was responsible for the above-mentioned changes of cytokine expression and M2 microglia polarization. Consistently, intraperitoneal injection of dexmedetomidine hydrochloride had a similar effect on microglia in the rat SCI model. Taken together, our study disclosed a novel mechanism underlying the anti-neuroinflammatory effect of dexmedetomidine: dexmedetomidine promotes AMPK signaling in activated microglia via upregulation of microglial PD-1 expression, and subsequently drives microglia polarization toward M2 type.

Effects of Different Ratio of n-6/n-3 Polyunsaturated Fatty Acids on the PI3K/Akt Pathway in Rats with Reflux Esophagitis.

BACKGROUND We designed this study to investigate the influence of different ratios of n-6/n-3 polyunsaturated fatty acid in the diet of reflux esophagitis (RE) rats' and the effect on the PI3K/Akt pathway. MATERIAL AND METHODS RE rats were randomly divided into a sham group and modeling groups of different concentrations of n-6/n-3 polyunsaturated fatty acid (PUFA): 12:1 group, 10:1 group, 5:1 group, and 1:1 group. RT-PCR and Western-blot were used to detect the expression of PI3K, Akt, p-Akt, NF-κBp50, and NF-κBp65 proteins in esophageal tissue. RESULTS In the n-6/n-3 PUFAs groups the expression of PI3K, Akt, p-Akt, nf-κbp50, and NF-κBp65 mRNA decreased with the decrease in n-6/n-3 ratios in the diet. The lowest expression of each indicator occurred in the 1:1 n-6/n-3 group compared with other n-6/n-3 groups, the difference was statistically significant (p<0.05). CONCLUSIONS The inhibition of n-3 PUFAs in the development of esophageal inflammation in rats with RE was attributed to the function of PI3K/Akt-NF-κB signaling pathway.

Methylene Blue Mitigates Acute Neuroinflammation after Spinal Cord Injury through Inhibiting NLRP3 Inflammasome Activation in Microglia.

The spinal cord injury (SCI) is a detrimental neurological disease involving the primary mechanical injury and secondary inflammatory damage. Curtailing the detrimental neuroinflammation would be beneficial for spinal cord function recovery. Microglia reside in the spinal cord and actively participate in the onset, progression and perhaps resolution of post-SCI neuroinflammation. In the current study, we tested the effects of methylene blue on microglia both in vitro and in a rat SCI model. We found that methylene blue inhibited the protein levels of IL-1ß and IL-18 rather than their mRNA levels in activated microglia. Further investigation indicated that methylene blue deceased the activation of NLRP3 inflammasome and NLRC4 inflammasome in microglia in vitro. Moreover, in the rat SCI model, the similar effect of methylene blue on post-SCI microglia was also observed, except that the activation of NLRC4 inflammasome was not seen. The inhibition of microglia NLRP3 inflammasome was associated with down-regulation of intracellular reactive oxygen species (ROS). The administration of methylene blue mitigated the overall post-SCI neuroinflammation, demonstrated by decreased pro-inflammatory cytokine production and leukocyte infiltrates. Consequently, the neuronal apoptosis was partially inhibited and the hind limb locomotor function was ameliorated by methylene blue treatment. Our research highlights the role of methylene blue in inhibiting post-SCI neuroinflammation, and suggests that methylene blue might be used for SCI therapy.

The 5-HT4 receptor agonist mosapride attenuates inflammation of reflux esophagitis.

BACKGROUND/AIMS: Chronic inflammatory processes and gastric contents related esophageal mucosal injury are two major characteristics of reflux esophagitis RE). This study was aimed to establish a rat model fitting RE major characteristics and to investigate the effects of mosapride, one of the 5-hydroxy tryptamine (5-HT)4 receptor agonists, on mucosal inflammation in RE. METHODOLOGY: Rat RE model was established by pyloric clip and section ligation-induced chronic acid reflux esophagitis. Animal body weight and survival was monitored. Animals were treated with 0.1 mg/kg/d, 0.5 mg/kg/d, or 2.5 mg/kg/d mosapride by gavage. Gastric emptying was examined. After two weeks, pathological changes of the esophagus were determined and endothelin-1 (ED-1) expression in esophageal tissues was evaluated by immunohistochemistry. RESULTS: No significant differences were observed in the gastric emptying of RE rats after different doses of mosapride treatment (P > 0.05). Gross examination and pathological evaluation revealed that either 0.5 mg/kg/d or 2.5 mg/kg/d mosapride treatment attenuated the mucosal inflammation of RE, but a lower mosapride dose (0.1 mg/kg/d) had limited esophagoprotective effects (P > 0.05). Mosapride treatment greatly decreased the number of ED-1 positive monocytes in the esophagus compared with sham-operated controls (P < 0.05). 5-HT4 receptor and acetylcholine (Ach) receptor antagonists effectively reversed the protective effects of mosapride (P < 0.05). CONCLUSIONS: Our results demonstrated that mosapride attenuated the mucosal inflammation of RE, suggesting that mosapride might provide esophagoprotective effects in addition to its well-known prokinetic actions.