Epigallocatechin Gallate Derivative Y6 Reverses Oxaliplatin Resistance in Hepatocellular Carcinoma via Targeting the MiR-338-3p/HIF-1α/TWIST Axis to Inhibit EMT.

BACKGROUND: The emergence of drug resistance to oxaliplatin (OXA) is one of the critical obstacles in the therapy of advanced Hepatocellular Carcinoma (HCC). As an ethyl derivative of the natural compound epigallocatechin gallate (epigallocatechin-3-gallate, EGCG), Y6 was found to be able to enhance the sensitivity of HCC cells to doxorubicin. This study aimed to investigate the effect of Y6 on oxaliplatin resistance in HCC. METHODS: MTT was used to determine the reversal effect of Y6 on OXA resistance. To further explore the reversal mechanism, we treated OXA alone or in combination with Y6 or EGCG in drugresistant cells and observed the morphological changes of the cells. At the same time, transwell assay was used to detect the invasion and migration ability of cells. Moreover, Real-time PCR and Western blot analysis were performed to determine the expression levels of the miR-338-3p gene, HIF-1α/Twist proteins, and EMT-related proteins. RESULTS: We found that Y6 could inhibit the proliferation of HCC cells and effectively reverse the drug resistance of oxaliplatin-resistant human liver cancer cells (SMMC-7721/OXA) to OXA, and the reversal effect was more significant than that of its lead drug EGCG. Most of the cells in the control group and OXA group showed typical mesenchymal-like cell morphology, while most of the cells in co-administration groups showed typical epithelioid cell morphology, and the ability of the cells to invade and migrate decreased dramatically, particularly in Y6 plus OXA group. At the same time, Y6 could up-regulate the EMT epithelial marker protein E-cadherin and down-regulate the interstitial marker protein Vimentin. In addition, in co-administration groups, the expression of miR-338-3p was up-regulated, while the expression of HIF-1α and Twist was down-regulated. CONCLUSION: Y6 significantly enhanced the susceptibility of drug-resistant cells to OXA, and the process may be related to the regulation of miR-338-3p/HIF-1α / TWIST pathway to inhibit EMT. Therefore, Y6 could be considered an effective medication resistance reversal agent, which could improve the therapeutic effect for hepatocellular cancer patients.

PI3K/AKT confers intrinsic and acquired resistance to pirtobrutinib in chronic lymphocytic leukemia.

PURPOSE: Pirtobrutinib, a non-covalent Bruton's tyrosine kinase (BTK) inhibitor, has been approved as the first agent to overcome resistance to covalent BTK inhibitors (such as ibrutinib, acalabrutinib, and zanubrutinib). However, the mechanisms of pirtobrutinib resistance in chronic lymphocytic leukemia (CLL) remain poorly understood. METHODS: To investigate pirtobrutinib resistance, we established resistant cell models using BTK knock-out via CRISPR-Cas9 or chronic exposure to pirtobrutinib in MEC-1 cells. These models mimicked intrinsic or acquired resistance, respectively. We then analyzed differential protein expression between wild-type (WT) and resistant MEC-1 cells using Revers Phase Protein microArray (RPPA) and confirmed the findings through Western Blot. Additionally, we evaluated potential drugs to overcome pirtobrutinib resistance by conducting cell proliferation assays, apoptosis studies, and animal experiments using both sensitive and resistant cells. RESULTS: MEC-1 cells developed resistance to pirtobrutinib either through BTK knock-out or prolonged drug exposure over three months. RPPA analysis revealed significant activation of proteins related to the PI3K/AKT pathway, including AKT and S6, in the resistant cells. Western Blot confirmed increased phosphorylation of AKT and S6 in pirtobrutinib-resistant MEC-1 cells. Notably, both the PI3K inhibitor (CAL101) and the AKT inhibitor (MK2206) effectively reduced cell proliferation and induced apoptosis in the resistant cells. The anti-tumor efficacy of these drugs was mediated by inhibiting the PI3K/AKT pathway. In vivo animal studies further supported the potential of targeting PI3K/AKT to overcome both intrinsic and acquired resistance to pirtobrutinib. CONCLUSION: The PI3K/AKT pathway plays a crucial role in both intrinsic and acquired resistance to pirtobrutinib in CLL. Therapeutically targeting this pathway may offer a promising strategy to overcome pirtobrutinib resistance.

Multicenter registry of multisystem inflammatory syndrome in children (MIS-C) and Paired comparison with Kawasaki disease.

OBJECTIVES: This study aimed to identify clinical characteristics to differentiate multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) in Taiwan, an island with a delayed cluster of MIS-C and a high incidence of KD. Additionally, we studied risk factors for developing severe complications in patients with MIS-C. METHODS: We conducted a retrospective, multicenter, cohort, and observational study that linked data on patients with MIS-C between May and December 2022 and patients with KD between 2019 and 2021 from 12 medical centers. Hemodynamic compromise, defined as the need for inotropic support or fluid challenge, was recorded in patients with MIS-C. We also evaluated maximal coronary Z-scores before treatment and one month after disease onset. RESULTS: A total of 83 patients with MIS-C and 466 patients with KD were recruited. A 1:1 age and gender-matched comparison of 68 MIS-C and KD pairs showed that MIS-C patients had a lower percentage of positive BCG red halos, lower leukocyte/platelet counts, more gastrointestinal symptoms, and a higher risk of hemodynamic compromise. In Taiwan, 38.6% of MIS-C patients experienced hemodynamic compromise, with presence of conjunctivitis and elevated levels of procalcitonin (>1.62 ng/mL) identified as independent risk factors. CONCLUSIONS: We identified two independent risk factors associated with hemodynamic compromise in MIS-C patients. The comparison between matched MIS-C and KD patients highlighted significant differences in clinical presentations, like BCG red halos, which may aid in the differential diagnosis of the two disease entities, especially in regions with a high incidence rate of KD.

Risk factors for AKI or mortality and long-term follow-up in COVID-19 infected patients in the era nefore vaccination.

BACKGROUND: Acute kidney injury (AKI) is a severe complication of coronavirus disease 2019 (COVID-19) and is associated with a higher risk of mortality. Understanding the risk factors contributing to COVID-19-related AKI and mortality before vaccination is important for the initiation of preventative measures and early treatment strategies. METHODS: This study included patients aged ≥18 years diagnosed with COVID-19 through polymerase chain reaction from May 2020 to July 2021, admitted in three local hospitals in Taiwan, with an extended follow-up until June 30, 2022. A median follow-up period of 250 days was used to assess AKI development and mortality. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. Multivariate Cox regression analysis of AKI and mortality-related risk factors was performed. RESULTS: Of the 720 hospitalized patients with COVID-19, 90 (22%) developed AKI. Moreover, 80%, 10.1%, and 8.9% of the patients had stage 1, 2, and 3 AKI, respectively. Patients with stage 1-3 AKI had significantly lower survival rates than those without AKI (p = 0.0012). The mean duration of post-admission AKI occurrence was 9.50 ± 11.32 days. Older age, hypoalbuminemia, and higher D-dimer and ferritin levels were associated with COVID-19 mortality. In COVID-19 AKI, in addition to older age and high D-dimer and ferritin levels, chronic kidney disease emerged as an independent risk factor. CONCLUSION: COVID-19-related AKI develops early, exhibits a temporal association with respiratory failure, and is linked to an unfavorable prognosis. The mortality rate increased according to the AKI stage (p = 0.0012). Age; albumin, D-dimer, and ferritin levels; and the underlying chronic kidney disease status upon admission are crucial factors for predicting AKI development, which increases the mortality risk. Monitoring the renal function not only within 10 days of COVID-19 onset, but also within one month after the disease onset.

Atrial flutter/fibrillation in adult congenital heart disease: Insights from a large Asian cohort.

BACKGROUND: The incidence of atrial fibrillation/atrial flutter (AF/AFL) in general population is lower in Asia compared to Western countries. It is unclear whether a similar trend exists among adults with congenital heart disease (ACHD). We determine the profile, risk factors, and impact of AF/AFL in an Asian ACHD cohort. METHODS: We included all ACHD patients diagnosed in an Asia tertiary care center between 2007 and 2018, analyzing AF (sustained and paroxysmal AF) and AFL, collectively./Purpose. RESULTS: The study encompassed 4391 patients (55.9% women), with 81% having simple, 16.3% moderate and 2.8% severe CHD. AF/AFL was observed in 6.7% of the patients, with 54.6% having paroxysmal AF, 27.3% sustained AF, and 18.1% AFL. Incidence of AF/AFL increased with age and was higher in patients with pulmonary hypertension (PH), severe CHD, and metabolic syndrome. We found a progressive trend in the onset age of arrhythmia: AFL at a younger age, followed by paroxysmal and sustained AF. Risk factors for AF/AFL included severe and moderate CHD, PH, previous interventions, and male sex (odds ratio 11.2 and 3.15, 2.03, 1.75, and 1.71, respectively). When stratifying by CHD severity, PH and male sex were significant risk factors in simple CHD, while only PH in severe CHD. Patients with AF/AFL had a significantly lower major adverse cardiovascular events-free survival rate. CONCLUSIONS: This large ACHD cohort from Asia exhibited a high incidence of AF/AFL, similar to Western reports. The risk of AF/AFL was primarily associated with hemodynamic factors such as PH and CHD severity.

[Two new pinophol derivatives from endophytic fungus Penicillium herquei JX4 hosted in Ceriops tagal].

An OSMAC strategy was used to study secondary metabolites and anti-inflammatory activities of the endophytic fungus Penicillium herquei JX4 hosted in Ceriops tagal. The PDB ferment of fungus P. herquei JX4 was isolated, purified, and identified by using silica gel column chromatography, gel column chromatography, octadecylsilyl(ODS) column chromatography, and semi-preparative high-performance liquid chromatography. Two new pinophol derivatives, pinophol H(1) and pinophol I(2) were isolated and identified, and they were evaluated in terms of the inhibitory activities against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse macrophage RAW264.7 cells. The results showed that compound 1 had significant inhibitory activity on NO production, with an IC_(50) value of 8.12 µmol·L~(-1).

Mechanism of Lian Hua Qing Wen capsules regulates the inflammatory response caused by M1 macrophage based on cellular experiments and computer simulations.

PURPOSE: The polarization of macrophages with the resulting inflammatory response play a crucial part in tissue and organ damage due to inflammatory. Study has proved Lian Hua Qing Wen capsules (LHQW) can reduce activation of inflammatory response and damage of tissue derived from the inflammatory reactions. However, the mechanism of LHQW regulates the macrophage-induced inflammatory response is unclear. Therefore, we investigated the mechanism of LHQW regulated the inflammatory response of M1 macrophages by cellular experiments and computer simulations. METHODS: This study has analysed the targets and mechanisms of macrophage regulating inflammatory response at gene and protein levels through bioinformatics. The monomeric components of LHQW were analyzed by High Performance Liquid Chromatography (HPLC). We established the in vitro cell model by M1 macrophages (Induction of THP-1 cells into M1 macrophages). RT-qPCR and immunofluorescence were used to detect changes in gene and protein levels of key targets after LHQW treatment. Computer simulations were utilized to verify the binding stability of monomeric components and protein targets. RESULTS: Macrophages had 140,690 gene targets, inflammatory response had 12,192 gene targets, intersection gene targets were 11,772. Key monomeric components (including: Pinocembrin, Fargesone-A, Nodakenin and Bowdichione) of LHQW were screened by HPLC. The results of cellular experiments indicated that LHQW could significantly reduce the mRNA expression of CCR5, CSF2, IFNG and TNF, thereby alleviating the inflammatory response caused by M1 macrophage. The computer simulations further validated the binding stability and conformation of key monomeric components and key protein targets, and IFNG/Nodakenin was able to form the most stable binding conformation for its action. CONCLUSION: In this study, the mechanism of LHQW inhibits the polarization of macrophages and the resulting inflammatory response was investigated by computer simulations and cellular experiments. We found that LHQW may not only reduce cell damage and death by acting on TNF and CCR5, but also inhibit the immune recognition process and inflammatory response by regulating CSF2 and IFNG to prevent polarization of macrophages. Therefore, these results suggested that LHQW may act through multiple targets to inhibit the polarization of macrophages and the resulting inflammatory response.

Quercetin protects against hypertensive renal injury by attenuating apoptosis: an integrated approach using network pharmacology and RNA-Seq.

Quercetin is kown for its antihypertensive effects. However, its role on hypertensive renal injury has not been fully eucidated. In this study, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining, and Annexin V staining were used to assess the pathological changes and cells apoptosis in the renal tissues of Ang II-infused mice and Ang II- stimulated renal tubular epithelial cell line (NRK-52E). A variety of technologies, including network pharmacology, RNA-sequencing, immunohistochemistry, and Western blotting were performed to investigate its underlying mechanisms. Network pharmacology analysis identified multiple potential candidate targets (including TP53, Bcl-2 and Bax) and enriched signaling pathways (including apoptosis and p53 signaling pathway). Quercetin treatment significantly alleviated the pathological changes in renal tissues of Ang II-infused mice and reversed 464 differentially expressed transcripts (DETs), as well as enriched several signaling pathways, including those related apoptosis and p53 pathway. Furthermore, quercetin treatment significantly inhibited the cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Additionally, quercetin treatment inhibited the upregulation of p53, Bax, cleaved-caspase-9, and cleaved-caspase-3 protein expression and the downregulation of Bcl-2 protein expression in both renal tissue of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Moreover, the molecular docking results indicated a potential binding interaction between quercetin and TP53. Quercetin treatment significantly attenuated hypertensive renal injury and cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells, and by targeting p53 may be one of the potential underlying mechanisms.

Comparison of Complication Rates Between Midline Catheters and Peripherally Inserted Central Catheters: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Midline catheters (MCs) and peripherally inserted central catheters (PICCs) are essential for reliable vascular access in patients. Despite their prevalent use, comparative risk assessments of these catheters, particularly from randomized controlled trials (RCTs), remain scarce. This meta-analysis primarily focuses on RCTs to evaluate and compare the incidence of complications associated with MCs and PICCs. METHODS: We conducted a comprehensive search of databases including the Cochrane Library, PubMed, Embase, Web of Science, ScienceDirect, Scopus, and ProQuest, up to April 2024. The primary outcomes analyzed were total complications and catheter-related bloodstream infections (CRBSIs), while secondary outcomes included catheter dwell time and thrombosis incidence. Meta-analyses were performed using a random-effects model. RESULTS: From 831 initially identified articles, 5 trials involving 608 patients met the inclusion criteria. MCs exhibited a significantly higher rate of total complications compared to PICCs (relative risk = 1.95, 95% confidence interval = 1.23-3.08, p = 0.005, I2= 0%). MCs also had shorter dwell times and a higher incidence of premature removal. However, no significant differences were observed in the rates of CRBSIs or thrombosis between MCs and PICCs. CONCLUSIONS: PICCs are associated with fewer total complications and longer dwell times compared to MCs, which tend to be more often removed prematurely. Thrombosis rates were similar between the two catheter types, underscoring the need for careful catheter selection based on specific patient conditions and treatment duration. Further research, particularly additional randomized controlled trials, is necessary to confirm these findings and guide optimal catheter selection in clinical practice.

Exploring Relationships of Heart Rate Variability, Neurological Function, and Clinical Factors with Mortality and Behavioral Functional Outcome in Patients with Ischemic Stroke.

Ischemic stroke is a leading cause of mortality and disability. The relationships of heart rate variability (HRV) and stroke-related factors with mortality and functional outcome are complex and not fully understood. Understanding these relationships is crucial for providing better insights regarding ischemic stroke prognosis. The objective of this study is to examine the relationship between HRV, neurological function, and clinical factors with mortality and 3-month behavioral functional outcome in ischemic stroke. We prospectively collected the HRV data and monitored the behavioral functional outcome of patients with ischemic stroke. The behavioral functional outcome was represented by a modified Rankin Scale (mRS) score. This study population consisted of 58 ischemic stroke patients (56.9% male; mean age 70) with favorable (mRS score ≤ 2) and unfavorable (mRS score ≥ 3) outcome. The analysis indicated that the median of the mean RR interval (RR mean) showed no statistical difference between mortality groups. Conversely, the median of the RR mean had significant association with unfavorable outcome (OR = 0.989, p = 0.007). Lower hemoglobin levels had significant association with unfavorable outcome (OR = 0.411, p = 0.010). Higher National Institute of Health Stroke Scale (NIHSS) score at admission had significant association with unfavorable outcome (OR = 1.396, p = 0.002). In contrast, age, stroke history, NIHSS score at admission, and hemoglobin showed no significant association with mortality in ischemic stroke. These results imply that HRV, as indicated by the median of RR mean, alongside specific clinical factors and neurological function at admission (measured by NIHSS score), may serve as potential prognostic indicators for 3-month behavioral functional outcome in ischemic stroke.

Liver fibrosis detected by diffusion-weighted magnetic resonance imaging and its functional correlates in Fontan patients.

OBJECTIVES: The evaluation of Fontan-associated liver disease is often challenging. Diffusion-weighted magnetic resonance imaging can detect hepatic fibrosis from capillary perfusion and diffusion abnormalities from extracellular matrix accumulation. This study investigated its role in the evaluation of liver disease in Fontan patients and explored possible diagnostic methods for early detection of advanced liver fibrosis. METHODS: Stable adult Fontan patients who could safely be examined with magnetic resonance imaging were enrolled, and blood biomarkers, transient elastography were also examined. RESULTS: Forty-six patients received diffusion-weighted imaging; and 58.7% were diagnosed with advanced liver fibrosis (severe liver fibrosis, 37.0%, and cirrhosis 21.7%). Two parameters of hepatic dysfunction, platelet counts (Spearman's ρ: -0.456, P = 0.001) and cholesterol levels (Spearman's ρ: -0.383, P = 0.009), decreased with increasing severity of fibrosis. Using transient elastography, a cut-off value of 14.2 kPa predicted the presence of advanced liver fibrosis, but with a low positive predictive value. When we included platelet count, cholesterol, post-Fontan years and transient elastography values as a composite, the capability of predicting advanced liver fibrosis was the most satisfactory (C statistic 0.817 ± 0.071, P < 0.001). A cut-off value of 5.0 revealed a sensitivity of 78% and a specificity of 82%. CONCLUSIONS: In Fontan patients, diffusion-weighted imaging was helpful in detecting liver fibrosis that was correlated with hepatic dysfunction. A simple score was proposed for long-term surveillance and early detection of advanced liver disease in adult Fontan patients. For adult Fontan patients with a calculated score > 5.0, we may consider timely diffusion-weight imaging and early management for liver complications.

Mitochondrial calcium uniporter knockdown in hippocampal neurons alleviates anxious and depressive behavior in the 3XTG Alzheimer's disease mouse model.

Alzheimer's disease (AD) is a progressive and degenerative disorder accompanied by emotional disturbance, especially anxiety and depression. More and more evidence shows that the imbalance of mitochondrial Ca2+ (mCa2+) homeostasis has a close connection with the pathogenesis of anxiety and depression. The Mitochondrial Calcium Uniporter (MCU), a key channel of mCa2+ uptake, induces the imbalance of mCa2+ homeostasis and may be a therapeutic target for anxiety and depression of AD. In the present study, we revealed for the first time that MCU knockdown in hippocampal neurons alleviated anxious and depressive behaviors of APP/PS1/tau mice through elevated plus-maze (EPM), elevated zero maze (EZM), sucrose preference test (SPT) and tail suspension test (TST). Western blot analysis results demonstrated that MCU knockdown in hippocampal neurons increased levels of glutamate decarboxylase 67 (GAD67), vesicular GABA transporter (vGAT) and GABAA receptor α1 (GABRA1) and activated the PKA-CREB-BDNF signaling pathway. This study indicates that MCU inhibition has the potential to be developed as a novel therapy for anxiety and depression in AD.

Phytochemical Research and Anti-inflammatory Activities of the Ethanol Extract from Anoectochilus roxburghii (Wall.) Lindl.

Anoectochilus roxburghii is a well-known and valuable traditional Chinese herb due to various medicinal and functional benefits. In-depth investigation is necessary to discover active ingredients and expand its application. In this study, four new compounds (1-4) along with ten known compounds (5-14) were isolated from the ethanol extract ofA.roxburghii. Their structures were elucidated by spectroscopic data interpretation. The isolates were screened for their inhibitory activities on the production of NO in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Among them, compounds 5, 6, 9, 10, 12, 13 and 14exhibited significant anti-inflammatory activity through inhibiting the release of NO.

Secular trend of Kawasaki disease and its correlation with viral activity in Taiwan: a nationwide population-based study.

BACKGROUND: Kawasaki disease (KD) is the most important acquired heart disease in children. This study investigated annual incidence, seasonality, secular trend and the correlation of KD incidence with viral activity in Taiwan. METHODS: Through the national health insurance database, we identified KD during 2001-2020. The viral activity was obtained from nationwide surveillance database. We analyzed KD age-specific annual incidence, secular trends, seasonality and the correlation between KD incidence and common enteric or respiratory viral activity. RESULTS: The KD incidence of subjects younger than 18 years significantly increased from 2001 to 2020 (11.78 and 22.40 per 100,000 person-years, respectively), and substantially decreased with age. Infants younger than 1 year presented the highest KD annual incidence at 105.82 to 164.34 per 100,000 person-years from 2001 to 2020. For all KD patients, the most frequently occurring season was summer followed by autumn. The KD incidence of infants younger than 1 year had significantly positive correlation with enteric (r = 0.14) and respiratory (r = 0.18) viral activity. CONCLUSIONS: This study demonstrates the increasing trend of KD annual incidence and seasonality (more in summer and autumn) in Taiwan. The activity of common respiratory and enteric viruses was significantly correlated with KD incidence in infants.

Green Synthesis of Carbon Quantum Dots and Carbon Quantum Dot-Gold Nanoparticles for Applications in Bacterial Imaging and Catalytic Reduction of Aromatic Nitro Compounds.

This study delves into the green synthesis and multifaceted applications of three types of carbon quantum dots (CQDs), namely, CQDs-1, CQDs-2, and CQDs-3. These CQDs were innovatively produced through a gentle pyrolysis process from distinct plant-based precursors: genipin with glucose for CQDs-1, genipin with extracted gardenia seeds for CQDs-2, and genipin with whole gardenia seeds for CQDs-3. Advanced analytical techniques, including X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FT-IR), were employed to detail the CQDs' structural and surface characteristics, revealing their unique functional groups and surface chemistries. The study further explores the CQDs' bioimaging potential, where confocal fluorescence microscopy evidenced their swift uptake by Escherichia coli bacteria, indicating their suitability for bacterial imaging. These CQDs were also applied in the synthesis of gold nanoparticles (AuNPs), acting as reducing agents and stabilizers. Among these, CQD3-AuNPs were distinguished by their remarkable stability and catalytic efficiency, achieving a 99.7% reduction of 4-nitrophenol to 4-aminophenol in just 10 min and maintaining near-complete reduction efficiency (99.6%) after 60 days. This performance notably surpasses that of AuNPs synthesized using sodium citrate, underscoring the exceptional capabilities of CQD3-AuNPs. These insights pave the way for leveraging CQDs and CQD-stabilized AuNPs in bacterial imaging and catalysis, presenting valuable directions for future scientific inquiry and practical applications.

A qualitative study of geriatric specialist nurses' experiences to navigate delirium in the elderly.

BACKGROUND: The experiences and perceptions of geriatric specialist nurses are pivotal to understanding the complexities of managing delirium and to developing effective nursing interventions. This qualitative study aims to explore these experiences and perceptions to inform the enhancement of clinical geriatric nursing and care practices. METHODS: Utilizing a qualitative exploratory design, this research engaged a convenience sample of geriatric specialist nurses at a tertiary hospital in Shanghai, China through focus groups and semi-structured interviews. Data were rigorously analyzed using Colaizzi's phenomenological method, which facilitated the identification of themes that emerged from the narratives of the geriatric specialist nurses. RESULTS: The thematic analysis yielded three major themes that encapsulate the nurses' experiences and perceptions. Theme 1: Understanding of Delirium, highlighted the nurses' awareness of the condition's significance, yet it was often deprioritized due to the pressing demands of managing more acute and immediately life-threatening conditions. Theme 2: Barriers in Application, brought to light the multifaceted challenges faced by nurses, including language barriers, the frequency and consistency of delirium assessments, the social determinants of health, and the nurses' own competencies in assessment. Theme 3: Evolution of Nursing Approaches, detailed the adaptive strategies employed by nurses, such as managing nursing adverse events, improving communication with patients' families, and adopting a proactive stance towards long-term patient outcomes. CONCLUSIONS: The findings suggest that while geriatric specialist nurses recognize the importance of delirium assessment, there are several barriers to effective application. The study underscores the imperative for the advancement of more refined delirium assessment and care protocols, tailored to address the unique requirements of geriatric nursing care.

Tracing the vertical migration of exogenous cadmium in soil by seasonal freeze-thaw event using rare earth elements.

Environmental behaviors of heavy metal in soil are strongly influenced by seasonal freeze-thaw events at the mid-high altitudes. However, the potential impact mechanisms of freeze-thaw cycles on the vertical migration of heavy metal are still poor understood. This study aimed to explore how exogenous cadmium (Cd) migrated and remained in soil during the in-situ seasonal freeze-thaw action using rare earth elements (REEs) as tracers. As a comparison, soil which was incubated in the controlled laboratory (25 °C) was employed. Although there was no statistically significant difference in the Cd levels of different soil depths under different treatments, the original aggregate sources of Cd in the 5-10 cm and 10-15 cm soil layers differed. From the distributions of REEs in soil profile, it can be known that Cd in the subsurface of field incubated soil was mainly from the breakdown of >0.50 mm aggregates, while it was mainly from the <0.106 mm aggregates for the laboratory incubated soil. Furthermore, the dissolved and colloidal Cd concentrations were 0.47 µg L-1 and 0.62 µg L-1 in the leachates from field incubated soil than those from control soil (0.21 µg L-1 and 0.43 µg L-1). Additionally, the colloid-associated Cd in the leachate under field condition was mainly from the breakdown of >0.25 mm aggregates and the direct migration of <0.106 mm aggregates, while it was the breakdown of >0.50 mm and the direct migration of <0.106 mm aggregates for the soil under laboratory condition. Our results for the first time provided insights into the fate of exogenous contaminants in seasonal frozen regions using the rare earth element tracing method.

Progress of Clinical Studies Targeting Claudin18.2 for the Treatment of Gastric Cancer.

Claudin18.2 is a tight junction protein, highly selective, generally expressed only in normal gastric mucosal epithelial cells, which can effectively maintain the polarity of epithelial and endothelial cells, thus effectively regulating the permeability and conductance of the paracellular pathway. Abnormal expression of Claudin18.2 can occur in various primary malignant tumors, especially gastrointestinal tumors, and even in metastatic foci. It regulates its expression by activating the aPKC/MAPK/AP-1 pathway, and therefore, the Claudin18.2 protein is a pan-cancer target expressed in primary and metastatic lesions in human cancer types. Zolbetuximab (IMAB362), an antibody specific for Claudin18.2, has been successfully tested in a phase III clinical trial, and the results of the study showed that combining Zolbetuximab with chemotherapy notably extends patients' survival and is expected to be a potential first-line treatment for patients with Claudin18.2(+)/HER-2(-) gastric cancer. Here, we systematically describe the biological properties and oncogenic effects of Claudin18.2, centering on its clinical-pathological aspects and the progress of drug studies in gastric cancer, which can help to further explore its clinical value.