Harnessing the Power of Sugar-Based Nanoparticles: A Drug-Free Approach to Enhance Immune Checkpoint Inhibition against Glioblastoma and Pancreatic Cancer.

Cancer cells have a high demand for sugars and express diverse carbohydrate receptors, offering opportunities to improve delivery with multivalent glycopolymer materials. However, effectively delivering glycopolymers to tumors while inhibiting cancer cell activity, altering cellular metabolism, and reversing tumor-associated macrophage (TAM) polarization to overcome immunosuppression remains a challenging area of research due to the lack of reagents capable of simultaneously achieving these objectives. Here, the glycopolymer-like condensed nanoparticle (∼60 nm) was developed by a one-pot carbonization reaction with a single precursor, promoting multivalent interactions for the galactose-related receptors of the M2 macrophage (TAM) and thereby regulating the STAT3/NF-κB pathways. The subsequently induced M2-to-M1 transition was increased with the condensed level of glycopolymer-like nanoparticles. We found that the activation of the glycopolymer-like condensed galactose (CG) nanoparticles influenced monocarboxylate transporter 4 (MCT-4) function, which caused inhibited lactate efflux (similar to inhibitor effects) from cancer cells. Upon internalization via galactose-related endocytosis, CG NPs induced cellular reactive oxygen species (ROS), leading to dual functionalities of cancer cell death and M2-to-M1 macrophage polarization, thereby reducing the tumor's acidic microenvironment and immunosuppression. Blocking the nanoparticle-MCT-4 interaction with antibodies reduced their toxicity in glioblastoma (GBM) and affected macrophage polarization. In orthotopic GBM and pancreatic cancer models, the nanoparticles remodeled the tumor microenvironment from "cold" to "hot", enhancing the efficacy of anti-PD-L1/anti-PD-1 therapy by promoting macrophage polarization and activating cytotoxic T lymphocytes (CTLs) and dendritic cells (DCs). These findings suggest that glycopolymer-like nanoparticles hold promise as a galactose-elicited adjuvant for precise immunotherapy, particularly in targeting hard-to-treat cancers.

Registered Nurses' Attitudes Towards ChatGPT and Self-Directed Learning: A Cross-Sectional Study.

BACKGROUND: Self-directed, lifelong learning is essential for nurses' competence in complex healthcare environments, which are characterised by rapid advancements in medicine and technology and nursing shortages. Previous studies have demonstrated that ChatGPT technology fosters self-directed learning by motivating users to engage with it. OBJECTIVES: To explore the relationships amongst socio-demographic data, attitudes towards ChatGPT use, and self-directed learning amongst registered nurses in Taiwan. METHODS: A cross-sectional study design with an online survey was adopted. Registered nurses from various healthcare settings were recruited through Facebook and LINE, a widely used messaging application in East Asia, reaching over 1000 nurses across five distinct online groups. An online survey was used to collect data, including socio-demographic characteristics, attitudes towards ChatGPT use, and a self-directed learning scale. Data were analysed using descriptive statistical methods, t-tests, Pearson's correlation, one-way analysis of variance, and multiple linear regression analysis. RESULTS: Amongst the 330 participants, 50.6% worked in hospitals, 51.8% had more than 15 years of work experience, and 78.2% did not hold supervisory positions. Of the participants, 46.7% had used ChatGPT. For all nurses, work experience and awareness of ChatGPT statistically significantly predicted self-directed learning, explaining 32.0% of the variance. For those familiar with ChatGPT, work experience in nursing and the technological/social influence of ChatGPT statistically significantly predicted self-directed learning, explaining 35.3% of the variance. CONCLUSIONS: Work experience in nursing provides critical opportunities for professional development and training. Therefore, ChatGPT-supported self-directed learning should be customised for degrees of experience to optimise continuous education. IMPLICATIONS FOR NURSING MANAGEMENT AND HEALTH POLICY: This study explores nurses' diverse use of and attitudes towards ChatGPT for self-directed learning. It suggests that administrators customise support and training when incorporating ChatGPT into professional development, accounting for nurses' varied experiences to enhance learning outcomes. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. REPORTING METHOD: This study adhered to the relevant cross-sectional STROBE guidelines.

Effects of dexamethasone on the EC50 of remifentanil combined with dexmedetomidine achieving analgesia during pancreatic extracorporeal shockwave lithotripsy: a prospective, randomized and controlled study.

BACKGROUND: In addition to their classic genomic effects, glucocorticoids also manifest rapid non genomic effects. We speculate that dexamethasone has the potential prompt onset of analgesic effects. The objective of this study is to investigate the influence of a single preoperative dose of dexamethasone on the half maximal effective concentration (EC50) of remifentanil when combined with dexmedetomidine for pain relief during pancreatic extracorporeal shockwave lithotripsy (P-ESWL). METHODS: A total of 60 patients undergoing P-ESWL were enrolled and randomized at 1:1 ratio into the dexamethasone (DXM) group and the placebo group. Before anesthesia induction, patients in DXM group received an intravenous injection of 8 mg dexamethasone, while subjects in placebo group received an equal dose of physiological saline. Monitored anesthesia care (MAC) was performed based on remifentanil in combination with dexmedetomidine. Remifentanil was administered by TCI with an initial target concentration of 2.5 µg/mL for both groups. A positive response was defined as that VAS score > 3 by the patient at any time during the procedure. Subsequent target concentrations were adjusted by Dixon up-down sequential method, where dose modifications were performed by 0.3 ng/mL intervals, based on the response of the previous patient. The EC50 of remifentanil for pain relief during P-ESWL treatment was calculated using Dixon's up-and-down method. Hemodynamic variables, oxygen saturation and adverse events were also recorded. RESULTS: Dixon up-and-down method revealed that the EC50 of remifentanil was significantly higher in placebo group (2.65 ± 0.28 ng/mL) than in DXM group (2.02 ± 0.23 ng/ml) (P < 0.001). Hemodynamic parameter exhibited a significant decrease in mean arterial pressure (MAP) and heart rate (HR) before and after induction in placebo group; however, data of the two groups were comparable (P>0.05). Less adverse events occurred in DXM group, including the incidence of postoperative nausea and vomiting (PONV) and analgesia requirement with in the first 24 h following the procedure at ward. CONCLUSION: Dexamethasone exerted analgesic effects with a rapid onset, and patients received dexamethasone 8 mg preoperative had a lower required EC50 of remifentanil during P-ESWL. It is also associated with reduced PONV in addition to reduced postoperative analgesic consumption in the first postoperative 24 h. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry (ChiCTR2300078171) on 30/11/2023.

Identification of a lactylation-related gene signature to characterize subtypes of hepatocellular carcinoma using bulk sequencing data.

Background: Prior studies indicate that lactylation regulates various biological mechanisms within cancer. However, lactylation-related genes (LRGs) have been found to have limited value in predicting the prognosis of hepatocellular carcinoma (HCC). The aim of this study was to review HCC LRGs using data from The Cancer Genome Atlas (TCGA). Methods: The RNA sequencing data and related clinical information of patients with HCC patients were collected from the TCGA database. A total of 20 LRGs were selected and bioinformatics analysis was performed. A consistency cluster analysis was conducted to classify the HCC tumors. Using a lactylation-related model of HCC, prognosis, immune cell infiltration, and immunotherapy was evaluated. Results: A total of 4,378 genes were associated with prognosis. Twenty LRGs (i.e., ACIN1, RAN, PPP1CB, ALDOB, SUMO2, THOC2, HDAC1, SF3A1, SF3B1, HNRNPM, PPP1CC, SRRM1, PRPF6, HDAC2, H2AFV, ALYREF, H2AFZ, H2AFX, HNRNPK, and MAGOH) were identified. The 20 LRGs were used to divide TCGA-HCC patients into low-risk (G1) and high-risk (G2) categories. The upregulated genes in the G1 group primarily participate in the p53 signaling pathway, focal adhesion, extracellular matrix (ECM)-receptor interaction, and cell cycle, while the downregulated genes primarily participate in the glycolysis/gluconeogenesis, carbon metabolism, and biosynthesis of amino acids. The box plots showed a significant difference in the immune cell populations, with a higher abundance of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and myeloid dendritic cells in the G1 than the G2 HCC samples. Further, the box plots showed higher expression levels of seven of the eight immune checkpoint inhibitor (ICI)-related genes in the G1 HCC samples than the G2 samples. There was a significant disparity in the cancer stem cell (CSC) scores between the G1 and G2 TCGA-HCC patients. Additionally, the G1 TCGA-HCC patients had higher tumor immune dysfunction and exclusion (TIDE) scores than the G2 TCGA-HCC patients. The prognosis of the HCC patients was also predicted using a six-LRG model, comprising HDAC2, SRRM1, SF3B1, HDAC1, THOC2, and PPP1CB. Conclusions: Strong correlation between LRGs and tumor classification as well as immunity in patients with HCC was identified. LRG signatures serve as reliable prognostic markers for HCC.

Performance of red blood cell indices for the detection of reticulocytosis in anemic and non-anemic dogs in Taiwan.

Reticulocyte counts (RETIC) are considered the gold standard in detecting an erythroid bone marrow response (BMR) in anemic and non-anemic dogs. Reticulocytosis without anemia (RWA) is a potential indicator of disease. The prevalence of anemia or RWA, as well as the effectiveness of red blood cell (RBC) indices in identifying a BMR, may vary based on geographical locations and breed differences. The purpose of the study was to determine the prevalence of regenerative and nonregenerative anemia, and RWA in pet dogs of Taiwan, and to assess the sensitivity and specificity of combined increased mean cell volume and decreased mean cell hemoglobin concentration (iMCV+dMCHC) to detect reticulocytosis in this population. The final population analysis consisted of 149,076 dogs. A cross sectional, retrospective analysis of complete blood count (CBC) samples from a field of automated hematology analyzers in Taiwan from December 1, 2018 through December 31, 2020 was performed. Among 149,076 dogs, 11.8 % (n=17,600) had reticulocytosis (RETIC > 110K/µl) and 21.8 % (n=32,474) had anemia (HCT < 37.3 %). Of 32,474 anemic dogs, 17.8 % (n=5,789) had reticulocytosis. Of 116,602 dogs without anemia, 10.1 % (n=11,776) had reticulocytosis. Across all dogs, sensitivity/specificity of iMCV+dMCHC to detect BMR was 4.3 % and 99.4 %, respectively compared to RETIC. Among anemic dogs, sensitivity/specificity of iMCV+dMCHC to detect BMR was 9.8 % and 99.2 %, respectively. Among non-anemic dogs, sensitivity/specificity of iMCV+dMCHC to detect BMR was 1.6 % and 99.5 %, respectively. Therefore, most regenerative anemias and cases of RWA did not have a combined iMCV+dMCHC. To avoid overlooking potential illness, RETIC should be evaluated regardless of whether patients have anemia or not.

Evaluation of the quality and readability of ChatGPT responses to frequently asked questions about myopia in traditional Chinese language.

Introduction: ChatGPT can serve as an adjunct informational tool for ophthalmologists and their patients. However, the reliability and readability of its responses to myopia-related queries in the Chinese language remain underexplored. Purpose: This study aimed to evaluate the ability of ChatGPT to address frequently asked questions (FAQs) about myopia by parents and caregivers. Method: Myopia-related FAQs were input three times into fresh ChatGPT sessions, and the responses were evaluated by 10 ophthalmologists using a Likert scale for appropriateness, usability, and clarity. The Chinese Readability Index Explorer (CRIE) was used to evaluate the readability of each response. Inter-rater reliability among the reviewers was examined using Cohen's kappa coefficient, and Spearman's rank correlation analysis and one-way analysis of variance were used to investigate the relationship between CRIE scores and each criterion. Results: Forty-five percent of the responses of ChatGPT in Chinese language were appropriate and usable and only 35% met all the set criteria. The CRIE scores for 20 ChatGPT responses ranged from 7.29 to 12.09, indicating that the readability level was equivalent to a middle-to-high school level. Responses about the treatment efficacy and side effects were deficient for all three criteria. Conclusions: The performance of ChatGPT in addressing pediatric myopia-related questions is currently suboptimal. As parents increasingly utilize digital resources to obtain health information, it has become crucial for eye care professionals to familiarize themselves with artificial intelligence-driven information on pediatric myopia.

miRNA-105-5p regulates the histone deacetylase HDAC2 through FOXG1 to affect the malignant biological behavior of triple-negative breast cancer cells.

BACKGROUND: Triple-negative breast cancer (TNBC) is a specific subtype of breast cancer (BC). Some potential molecular targets have been identified, and miR-105-5p was found to be abnormally expressed in TNBC tissues. OBJECTIVE: The objective of this study was to probe the effect of miR-105-5p on TNBC via FOXG1/HDAC2-mediated acetylation. METHODS: An animal model of TNBC was established by injecting BC cells into the axillary area of nude mice. The levels of miR-105-5p, FOXG1, HDAC2, Bcl-2, Bax, and Ki67 were detected via RT‒qPCR, Western blotting and immunohistochemistry. Flow cytometry, CCK-8, Transwell and colony formation assays were used to measure apoptosis, proliferation and migration, respectively. Total histone acetylation levels were measured by ELISA. The binding of FOXG1 to HDAC2 was detected by co-immunoprecipitation. The binding relationship between miR-105-5p and FOXG1 was verified using a dual-luciferase reporter gene assay. RESULTS: In this study, miR-105-5p and HDAC2 were highly expressed in the MDA-MB-231 and BT-549 BC cell lines, whereas FOXG1 was expressed at low levels. The inhibition of miR-105-5p inhibited the proliferation and migration of MDA-MB-231 and BT-549 cells and promoted their apoptosis. Bioinformatics analysis revealed that miR-105-5p and FOXG1 had a negative targeting regulatory relationship. FOXG1 overexpression had a similar effect on cancer cells as the inhibition of miR-105-5p. Moreover, experiments revealed that FOXG1 and HDAC2 could bind to each other and that HDAC2 overexpression or treatment with the histone acetyltransferase inhibitor Garcinol weakened the effect of FOXG1 overexpression. In addition, FOXG1 knockdown inhibited the effect of the miR-105-5p inhibitor, while Garcinol treatment further enhanced the effect of FOXG1 knockdown, inhibited histone acetylation, promoted the proliferation and migration of cancer cells, and inhibited apoptosis. Moreover, the in vivo results confirmed the in vitro results. CONCLUSION: miR-105-5p promotes HDAC2 expression by reducing FOXG1, inhibits histone acetylation, and aggravates the malignant biological behavior of TNBC cells.

Efficacy of intravenous iron supplementation in reducing transfusion risk following cardiac surgery: an updated meta-analysis of randomised controlled trials.

BACKGROUND: Previous meta-analyses of intravenous iron supplementation for reducing red blood cell (RBC) transfusion risk after cardiac surgery were inconclusive because of limited data. This updated meta-analysis incorporates recent evidence. METHODS: Major databases were searched on May 2, 2024 for randomised controlled trials comparing the incidence of RBC transfusion between adult patients receiving intravenous iron supplementation and those receiving controls (i.e. oral iron or placebo) after cardiac surgery. The secondary outcomes included the number of RBC units transfused, postoperative haemoglobin levels, iron status, complications, and length of hospital stay. Trial sequential analysis was conducted to examine the robustness of evidence. RESULTS: Fourteen randomised controlled trials including 2043 subjects were identified. Intravenous iron supplementation was found to reduce the RBC transfusion risk compared with controls (relative risk 0.77, 95% confidence interval [CI] 0.65-0.91, P=0.002, n=1955, I2=61%, certainty of evidence: moderate). The trial sequential analysis supported the robustness of the evidence. Furthermore, haemoglobin levels were higher in the intravenous iron supplementation group on postoperative days 4-10 (mean difference 0.17 g dl-1, 95% CI 0.06-0.29, n=1989) and >21 days (mean difference 0.66 g/dl-1, 95% CI 0.36-0.95, n=1008). Postoperative iron status also improved with Intravenous iron supplementation, particularly on postoperative days 4-10. There were no significant differences in other outcomes, including mortality. CONCLUSIONS: Intravenous iron supplementation can reduce RBC transfusion risk and improve postoperative haemoglobin level and iron status after cardiac surgery, supporting the implementation of Intravenous iron supplementation in perioperative blood management strategies. SYSTEMATIC REVIEW PROTOCOL: CRD42024542206 (PROSPERO).

Precision matters: the value of PET/CT and PET/MRI in the clinical management of cervical cancer.

The incidence of cervical cancer has been increasing recently, becoming an essential factor threatening patients' health. Positron emission computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI) are multimodal molecular imaging methods that combine functional imaging (PET) and anatomical imaging (CT) with MRI fusion technology. They play an important role in the clinical management of patients with cervical cancer. Precision radiotherapy refers to the use of advanced intensive modulated radiotherapy (IMRT) to give different doses of radiation to different treatment areas to achieve the purpose of killing tumors and protecting normal tissues to the greatest extent. At present, pelvic target delineation is mostly based on CT and MRI, but these mostly provide anatomical morphological information, which is difficult to show the internal metabolism of tumors. PET/CT and PET/MRI combine information on biological function, metabolism and anatomical structure, thereby more accurately distinguishing the boundaries between tumor and non-tumor tissues and playing a positive guiding role in improving radiotherapy planning (RTP) for cervical cancer and evaluating treatment effect.

Predictive value of polygenic risk score for prostate cancer incidence and prognosis in the Han Chinese.

Although prostate cancer is a common occurrence among males, the relationship between existing risk prediction models remains unclear. The objective of this hospital-based retrospective study is to investigate the impact of polygenic risk scores (PRSs) on the incidence and prognosis of prostate cancer in the Han Chinese population. A total of 24,778 male participants including 903 patients with prostate cancer at Taichung Veterans General Hospital were enrolled in the study. PRS was calculated using 269 single nucleotide polymorphisms and their corresponding effect sizes from the polygenic score catalog. The association between PRS and the risk prostate cancer was evaluated using Cox proportional hazards regression model. Among the 24,778 participants, 903 were diagnosed with prostate cancer. The risk of prostate cancer was significantly higher in the highest quartile of PRS distribution compared to the lowest (hazard ratio = 4.770, 95% CI = 3.999-5.689, p < 0.0001), with statistical significance across all age groups. Patients in the highest quartile were diagnosed with prostate cancer at a younger age (66.8 ± 8.3 vs. 69.5 ± 8.8, p = 0.002). Subgroup analysis of patients with localized or stage 4 prostate cancer showed no significant differences in biochemical failure or overall survival. This hospital-based cohort study observed that a higher PRS was associated with increased susceptibility to prostate cancer and younger age of diagnosis. However, PRS was not found to be a significant predictor of disease stage and prognosis. These findings suggest that PRS could serve as a useful tool in prostate cancer risk assessment.

Impact of Time Period and Birth Cohort on the Trend of Advanced Neoplasm Prevalence in the 40-49 Average-Risk Screening Population.

BACKGROUND AND AIMS: Early-onset colorectal cancer (CRC) is increasing globally. While the United States have lowered the age of initiation of screening to 45 years, other countries still start screening at 50 years of age. In Taiwan, the incidence of CRC has declined in 55- to 74-year-olds after the initiation of screening, but still increased in those 50-54 years of age, potentially due to rising precancerous lesion incidence in 40- to 49-year-olds. This study aimed to explore the chronological trend of the prevalence of colorectal advanced neoplasms (AN) in the screening population 40-54 years of age. METHODS: We retrospectively analyzed a screening colonoscopy cohort for prevalence of AN in average-risk subjects 40-54 years of age from 2003 to 2019. Logistic regression was used to distinguish cohort effect from time-period effect on the prevalence of AN. RESULTS: In total, 27,805 subjects (52.1% male) men were enrolled. There were notable increases in prevalence of AN in all 3 age groups during the 17-year span, but these were more rapid in those 40-44 years of age (0.99% to 3.22%) and 45-49 years of age (2.50% to 4.19%). Those 50-54 years of age had a higher risk of AN (adjusted odds ratio [aOR], 1.62; 95% confidence interval [CI], 1.19-2.19) in 2003-2008 but not in later periods (2009-2014: aOR, 1.08; 95% CI, 0.83-1.41; 2015-2019: aOR, 0.76; 95% CI, 0.56-1.03) when compared with those 45-49 years of age. CONCLUSION: The prevalence of AN in those 40-54 years of age increased in the Taiwanese population, with a later birth cohort having a higher prevalence of AN. However, the prevalence of AN in those 45-49 years of age increased more remarkably and approximated that in those 50-54 years of age, which may justify earlier initiation of CRC screening in those 45 years of age.

The Effect of Novel AI-based Cecum Recognition System on Adenoma Detection Metrics at Screening Colonoscopy Setting.

BACKGROUND AND AIMS: Cecal intubation of colonoscopy relies on self-reporting. We developed an artificial intelligence-based cecum recognition system (AI-CRS) for post hoc verification of cecal intubation and explored its impact on adenoma metrics. METHODS: Quality metrics, including cecal intubation rate (CIR), adenoma detection rate (ADR), and other ADR-related metrics were compared both before (2015-2018) and after (2019-2022) the implementation of AI-CRS. RESULTS: While CIR did not change significantly after the implementation of AI-CRS, ADR and AADR significantly increased. While ADR significantly increased in all segments, the most significant increase in AADR was observed in the proximal colon. Implementation of AI-CRS was associated with a higher likelihood of detecting adenoma (aOR=1.35, 95%CI=1.26-1.45) and advanced adenoma (aOR=1.23, 95%CI=1.07-1.41), respectively. CONCLUSIONS: Implementation of a post hoc verification of cecal intubation using an AI-CRS significantly improved various adenoma metrics in screening colonoscopy.

Outbreak preparedness and response strategies in ASEAN member states: a scoping review.

Objectives: The 21st century has witnessed significant disease outbreaks with severe impact in Association of Southeast Asian Nations (ASEAN) countries, including SARS, H1N1, H5N1, and COVID-19. This review aimed to compile and analyze outbreak preparedness and response strategies, highlighting the success of coordinated multi-sectoral approaches and policy responses within the ASEAN region. Methods: The protocol for this review was registered on the Open Science Framework and PROSPERO. A systematic analysis of publications from the 2002-2022 period was conducted following PRISMA guidelines on 4522 records retrieved from PubMed, CINAHL, Web of Science, and Scopus. The titles and abstracts were screened, and 229 articles were selected for full-text screening. Finally, 34 articles were included in this review. Results: Four preparedness pillars were identified: governance and stewardship, disease detection, disease prevention, and health care management. The pillars were crucial in preparing for and responding to the COVID-19 pandemic. Coordinated responses among the ASEAN countries and local and international stakeholders were reported. Conclusions: The findings emphasize that understanding the transmission dynamics of infectious diseases is paramount for effective disease prevention, surveillance, and timely response efforts to prevent the next pandemic. A well-coordinated multi-country and multi-agency policy response and understanding the different disease management models are crucial in addressing future outbreaks in the region. Future post-pandemic publications will shed more light on lessons learned and preparedness and response plans for future pandemics.

Impact of intravenous steroids on subjective recovery quality after surgery: A meta-analysis of randomized clinical trials.

STUDY OBJECTIVE: Quality of postoperative recovery is a crucial aspect of perioperative care. This meta-analysis aimed to evaluate the efficacy of intravenous steroids in improving the quality of recovery (QoR) after surgery, as measured by validated QoR scales. DESIGN: Meta-analysis of randomized controlled trials (RCTs). SETTING: Operating room. INTERVENTION: The use of a single dose of intravenous steroids as a supplement to general anesthesia. PATIENTS: Adult patients undergoing surgery. MEASUREMENTS: A literature search was conducted using electronic databases (e.g., MEDLINE and Embase) from their inception to June 2024. Randomized controlled trials (RCTs) comparing intravenous steroids with placebo or no treatment in adult patients undergoing surgery under general anesthesia were included. The primary outcome was the QoR scores on postoperative days (POD) 1 and 2-3, as assessed by validated QoR scales (QoR-15 and QoR-40). Secondary outcomes included QoR dimensions, analgesic rescue, pain scores, and postoperative nausea and vomiting (PONV). MAIN RESULTS: Eleven RCTs involving 951 patients were included in this study. The steroid group showed significant improvements in global QoR scores on POD 1 (standardized mean difference [SMD]: 0.52; 95 % confidence interval[CI]: 0.22 to 0.82; P = 0.0007) and POD 2-3 (SMD: 0.50; 95 % CI: 0.19 to 0.81; P = 0.001) compared to the control group. Significant improvements were also observed in all QoR dimensions on POD 1, with the effect sizes ranging from small to moderate. Intravenous steroids also significantly reduced the analgesic rescue requirements (RR: 0.77; 95 % CI: 0.67 to 0.88; P = 0.0003), postoperative pain scores (SMD: -0.41; 95 % CI: -0.68 to -0.14; P = 0.003), and PONV incidence (RR: 0.73; 95 % CI: 0.56 to 0.95; P = 0.02). CONCLUSIONS: Intravenous administration of steroids significantly improved QoR after surgery. The benefits of steroids extend to all dimensions of QoR and important clinical outcomes such as analgesic requirements, pain scores, and PONV. These findings support the use of steroids as an effective strategy to enhance the postoperative recovery quality.

Prognostic Significance of VAV3 Gene Variants and Expression in Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is characterized by high mortality and morbidity rates. Vav guanine nucleotide exchange factors (VAVs), crucial for signal transduction between cell membrane receptors and intracellular mediators, have been implicated in carcinogenesis. However, their potential prognostic value in RCC remains unclear. The impact of 150 common VAV polymorphisms on RCC risk and survival was investigated in a cohort of 630 individuals. Publicly available gene expression datasets were utilized to analyze VAV gene expression in relation to patient outcomes. The VAV3 rs17019888 polymorphism was significantly associated with RCC risk and overall survival after adjusting for false discovery rates. Expression quantitative trait loci analysis revealed that the risk allele of rs17019888 is linked to reduced VAV3 expression. Analysis of 19 kidney cancer gene expression datasets revealed lower VAV3 expression in RCC tissues compared to normal tissues, with higher expression correlating with better prognosis. Gene set enrichment analysis demonstrated that VAV3 negatively regulates the ubiquitin-proteasome system, extracellular matrix and membrane receptors, inflammatory responses, matrix metalloproteinases, and cell cycle pathways. Furthermore, elevated VAV3 expression was associated with increased infiltration of B cells, macrophages, and neutrophils into the RCC tumor microenvironment. Our findings suggest that VAV3 gene variants influence RCC risk and survival, contributing to a favorable prognosis in RCC.

A systematic review on Nipah virus: global molecular epidemiology and medical countermeasures development.

Nipah virus (NiV) is an emerging pathogen that causes encephalitis and a high mortality rate in infected subjects. This systematic review aimed to comprehensively analyze the global epidemiology and research advancements of NiV to identify the key knowledge gaps in the literature. Articles searched using literature databases, namely PubMed, Scopus, Web of Science, and Science Direct yielded 5,596 articles. After article screening, 97 articles were included in this systematic review, comprising 41 epidemiological studies and 56 research developments on NiV. The majority of the NiV epidemiological studies were conducted in Bangladesh, reflecting the country's significant burden of NiV outbreaks. The initial NiV outbreak was identified in Malaysia in 1998, with subsequent outbreaks reported in Bangladesh, India, and the Philippines. Transmission routes vary by country, primarily through pigs in Malaysia, consumption of date palm juice in Bangladesh, and human-to-human in India. However, the availability of NiV genome sequences remains limited, particularly from Malaysia and India. Mortality rates also vary according to the country, exceeding 70% in Bangladesh, India, and the Philippines, and less than 40% in Malaysia. Understanding these differences in mortality rate among countries is crucial for informing NiV epidemiology and enhancing outbreak prevention and management strategies. In terms of research developments, the majority of studies focused on vaccine development, followed by phylogenetic analysis and antiviral research. While many vaccines and antivirals have demonstrated complete protection in animal models, only two vaccines have progressed to clinical trials. Phylogenetic analyses have revealed distinct clades between NiV Malaysia, NiV Bangladesh, and NiV India, with proposals to classify NiV India as a separate strain from NiV Bangladesh. Taken together, comprehensive OneHealth approaches integrating disease surveillance and research are imperative for future NiV studies. Expanding the dataset of NiV genome sequences, particularly from Malaysia, Bangladesh, and India will be pivotal. These research efforts are essential for advancing our understanding of NiV pathogenicity and for developing robust diagnostic assays, vaccines and therapeutics necessary for effective preparedness and response to future NiV outbreaks.

Synergistic ROS Generation via Core-Shell Nanostructures with Increased Lattice Microstrain Combined with Single-Atom Catalysis for Enhanced Tumor Suppression.

This study emphasizes the innovative application of FePt and Cu core-shell nanostructures with increased lattice microstrain, coupled with Au single-atom catalysis, in significantly enhancing •OH generation for catalytic tumor therapy. The combination of core-shell with increased lattice microstrain and single-atom structures introduces an unexpected boost in hydroxyl radical (•OH) production, representing a pivotal advancement in strategies for enhancing reactive oxygen species. The creation of a core-shell structure, FePt@Cu, showcases a synergistic effect in •OH generation that surpasses the combined effects of FePt and Cu individually. Incorporating atomic Au with FePt@Cu/Au further enhances •OH production. Both FePt@Cu and FePt@Cu/Au structures boost the O2 → H2O2 → •OH reaction pathway and catalyze Fenton-like reactions. This enhancement is underpinned by DFT theoretical calculations revealing a reduced O2 adsorption energy and energy barrier, facilitated by lattice mismatch and the unique catalytic activity of single-atom Au. Notably, the FePt@Cu/Au structure demonstrates remarkable efficacy in tumor suppression and exhibits biodegradable properties, allowing for rapid excretion from the body. This dual attribute underscores its potential as a highly effective and safe cancer therapeutic agent.

Improving the Purity of Extracellular Vesicles by Removal of Lipoproteins from Size Exclusion Chromatography- and Ultracentrifugation-Processed Samples Using Glycosaminoglycan-Functionalized Magnetic Beads.

Extracellular vesicles (EVs) are present in blood at much lower concentrations (5-6 orders of magnitude) compared to lipoprotein particles (LP). Because LP and EV overlap in size and density, isolating high-purity EVs is a significant challenge. While the current two-step sequential EV isolation process using size-expression chromatography (SEC) followed by a density gradient (DG) achieves high purity, the time-consuming ultracentrifugation (UC) step in DG hinders workflow efficiency. This paper introduces an optimized magnetic bead reagent, LipoMin, functionalized with glycosaminoglycans (GAGs), as a rapid alternative for LP removal during the second-step process in about 10 minutes. We evaluated LipoMin's efficacy on two sample types: (a) EV fractions isolated by size exclusion chromatography (SEC + LipoMin) and (b) the pellet obtained from ultracentrifugation (UC + LipoMin). The workflow is remarkably simple, involving a 10 min incubation with LipoMin followed by magnetic separation of the LP-depleted EV-containing supernatant. Results from enzyme-linked immunosorbent assay (ELISA) revealed that LipoMin removes 98.2% ApoB from SEC EV fractions, comparable to the LP removal ability of DG in the SEC + DG two-step process. Importantly, the EV yield (CD81 ELISA) remained at 93.0% and Western blot analysis confirmed that key EV markers, flotillin and CD81, were not compromised. Recombinant EV (rEV), an EV reference standard, was spiked into SEC EV fractions and recovered 89% of CD81 protein. For UC + LipoMin, ApoA1 decreased by 76.5% while retaining 90.7% of CD81. Notably, both colorectal cancer (CRC) and Alzheimer's disease (AD) samples processed by SEC + LipoMin and UC + LipoMin displayed clear expression of relevant EV and clinical markers. With a 10 min workflow (resulting in a 96% time saving compared to the traditional method), the LipoMin reagent offers a rapid and efficient alternative to DG for LP depletion, paving the way for a streamlined SEC + LipoMin two-step EV isolation process.