Boosting selective Cs+ uptake through the modulation of stacking modes in layered niobate-based perovskites.

Selective separation of 137Cs is significant for the sustainable development of nuclear energy and environmental protection, due to its strong radioactivity and long half-life. However, selective capture of 137Cs+ from radioactive liquid waste is challenging due to strong coulomb interactions between the adsorbents and high-valency metal ions. Herein, we propose a strategy to resolve this issue and achieve specific Cs+ ion recognition and separation by modulating the stacking modes of layered perovskites. We demonstrate that among niobate-based perovskites, ALaNb2O7 (A = Cs, H, K, and Li), HLaNb2O7 shows an outstanding selectivity for Cs+ even in the presence of a large amount of competing Mn+ ions (Mn+ = K+, Ca2+, Mg2+, Sr2+, Eu3+, and Zr4+) owing to its suitable void fraction and space shape, brought by the stacking mode of layers. The Cs+ capture mechanism is directly elucidated at molecular level by single-crystal structural analyses and density functional theory calculations. This work not only provides key insights in the design and property optimization of perovskite-type materials for radiocesium separation, but also paves the way for the development of efficient inorganic materials for radionuclides remediation.

Cardiac macrophages in maintaining heart homeostasis and regulating ventricular remodeling of heart diseases.

Macrophages are most important immune cell population in the heart. Cardiac macrophages have broad-spectrum and heterogeneity, with two extreme polarization phenotypes: M1 pro-inflammatory macrophages (CCR2-ly6Chi) and M2 anti-inflammatory macrophages (CCR2-ly6Clo). Cardiac macrophages can reshape their polarization states or phenotypes to adapt to their surrounding microenvironment by altering metabolic reprogramming. The phenotypes and polarization states of cardiac macrophages can be defined by specific signature markers on the cell surface, including tumor necrosis factor α, interleukin (IL)-1ß, inducible nitric oxide synthase (iNOS), C-C chemokine receptor type (CCR)2, IL-4 and arginase (Arg)1, among them, CCR2+/- is one of most important markers which is used to distinguish between resident and non-resident cardiac macrophage as well as macrophage polarization states. Dedicated balance between M1 and M2 cardiac macrophages are crucial for maintaining heart development and cardiac functional and electric homeostasis, and imbalance between macrophage phenotypes may result in heart ventricular remodeling and various heart diseases. The therapy aiming at specific target on macrophage phenotype is a promising strategy for treatment of heart diseases. In this article, we comprehensively review cardiac macrophage phenotype, metabolic reprogramming, and their role in maintaining heart health and mediating ventricular remodeling and potential therapeutic strategy in heart diseases.

Efficacy of respiratory support therapies during pulmonary rehabilitation exercise training in chronic obstructive pulmonary disease patients: a systematic review and network meta-analysis.

BACKGROUND: Exercise training is fundamental in pulmonary rehabilitation (PR), but patients with chronic obstructive pulmonary disease (COPD) often struggle with exercise intolerance. Respiratory support during exercise in COPD patients may be a beneficial adjunct therapy. In this study, the effect of different respiratory support therapy during pulmonary rehabilitation exercise training in COPD patients was assessed through a network meta-analysis. METHODS: Five databases were searched to obtain randomized controlled trials involving different respiratory support therapies during PR exercise training in COPD patients. The Cochrane Handbook tool was employed to assess the risk bias of included studies. Network meta-analysis was performed using the STATA software. The study protocol was registered at PROSPERO (CRD42023491139). RESULTS: A total of 35 studies involving 1321 patients and 6 different interventions were included. Network meta-analysis showed that noninvasive positive pressure ventilation (NPPV) is superior in improving exercise capacity (6-Minute Walk Test distance, peak work rate, endurance time), dyspnea, and physiological change (peak VO2, tidal volume, minute ventilation and lactate level) in stable COPD patients who were at GOLD stage III or IV during PR exercise training. The final surface under the cumulative ranking curve value indicated that NPPV therapy achieved the best assistive rehabilitation effect. CONCLUSIONS: The obtained results indicate that NPPV is most powerful in assisting exercise in severe COPD patients under stable condition. Researchers should focus more on the safety, feasibility, and personalization of interventions. Furthermore, there is a need for additional high-quality trials to assess the consistency of evidence across various respiratory support approaches. TRIAL REGISTRATION: The study was registered at PROSPERO (CRD42023491139).

Reliability and validity of the Chinese version of the Benefit Finding Questionnaire for people with mental disorders.

BACKGROUND: Benefit finding (BF) is correlated with mental health and recovery, and its presence will contribute to the recovery of patients with mental disorders. Most of the current tools for assessing BF in patients with somatic disorders are not adequate for patients with mental disorders. The present study proposes to introduce the Benefit Finding Questionnaire for People with Mental Disorders and to validate its psychometric properties. METHODS: The Beaton translation model was used to translate and cross-culturally adjust the Japanese version of the Benefit Finding Questionnaire for People with Mental Disorders. A survey of 514 people with mental disorders was conducted from January 2022 to October 2022 using a general information questionnaire and a translated Chinese version of the Benefit Finding Questionnaire for People with Mental Disorders (BFQ-C) using a convenience sampling method. The quality of the questionnaire was examined in terms of item analysis, reliability, and validity. RESULTS: The results of the item analysis showed that all items met the requirements. The interrater agreement of the BFQ-C was good, with an interrater agreement = 0.714; the values of the item-level content validity index ranged from 0.75 to 1.00; and the average of all item-level content validity index on the scale = 0.958. Exploratory factor analysis extracted three main factors "change in relationship with others," "change in spirituality," and "change in values and thinking styles"-and the cumulative variance contribution rate was 57.70%. The results of the confirmatory factor analysis were χ2/df of 2.194, Root Mean Square Error of Approximation of 0.075, and comparative fit index of 0.919, indicating that the model fitted well. The questionnaire had a Cronbach' alpha of 0.936, a split reliability of 0.956, and a retest reliability of 0.939. CONCLUSION: The BFQ-C demonstrated good reliability and validity, and can be used to assess the BF level of people with mental disorders (e.g., anxiety disorders, depressive disorders, schizophrenia, and bipolar disorders) in China.

Simplified Chinese Trauma Advanced Practice Nurses' Core Competency Scale: A development and psychometric validation study.

BACKGROUND: The core competency of trauma advanced practice nurses (APNs) is directly related to the quality of trauma nursing work. OBJECTIVES: To develop an instrument to measure trauma APNs' core competency and examine its psychometric properties. DESIGN: A cross-sectional psychometric validation study. PARTICIPANTS: A total of 762 trauma nurses recruited from several tertiary hospitals in 14 different provinces of China between June 2023 and May 2024 provided valid data for analysis. METHODS: The Simplified Chinese Trauma Advanced Practice Nurses' Core Competency Scale (TAPNCCS-SC) was developed through five steps. Step 1) Creation of the operational definition: Based on the onion model, an operational definition of core competencies for trauma nurses is proposed. Step 2) Item generation: Based on the theoretical model, literature review, semi-structured interviews, and Delphi consultation, a preliminary scale was developed. Step 3) Item content validation: 6 experts reviewed items for content validity; Step 4) Pilot study: 21 nurses were selected to test the readability of the preliminary scale; and Step 5) Psychometric evaluation: Item analysis, content validity, exploratory and confirmatory factor analyses, convergent validity, internal consistency reliability, and half-reliability were conducted. RESULTS: The TAPNCCS-SC consists of 34 items and three dimensions (knowledge and skills, professional competencies, and occupational qualities). The explained variance of the 3-factor was 81.86 %. The CFA showed an acceptable-fitting 3-factor model (χ2/df = 3.653, RMSEA = 0.088, SRMR = 0.402, CFI = 0.920, IFI = 0.920, and TLI = 0.914). For convergent validity, AVE was 0.784-0.804 and CR was 0.974-0.980. The internal consistency and split-half reliability for the total scale were 0.991 and 0.945, respectively. The I-CVI ranged from 0.83 to 1. CONCLUSIONS: The proposed scale exhibits high reliability and validity and is suitable for assessing the core competency of trauma APNs, which can help nursing managers plan relevant training and enhance trauma care competency.

CIB2 mediates acquired gefitinib resistance by inducing ZEB1 expression and epithelial-mesenchymal transition.

EGFR-TKIs have been used as frontline treatment in patients with advanced non-small cell lung cancer (NSCLC) suffering from the EGFR mutation. Gefitinib, the first-generation EGFR-TKI, has greatly improved survival rates in lung cancer patients, whereas acquired gefitinib resistance is still a critical issue that needs to be overcome. In our research, high expression levels of CIB2 were found in gefitinib-resistant lung cancer cells. CIB2 knockout rendered gefitinib-resistant cells more sensitive to gefitinib, and overexpression of CIB2 in parental cells was sufficient to induce more resistance to gefitinib. Inhibition of CIB2 in gefitinib-resistant lung cancer cells significantly induced cell apoptosis. To clarify the major molecular mechanism by which CIB2 increases gefitinib resistance, we demonstrated that raised CIB2 in lung cancer cells promoted epithelial-to-mesenchymal transition (EMT) through upregulation of ZEB1. Moreover, FOSL1 transcriptionally regulated CIB2 expression. Finally, CIB2 rendered tumors resistant to gefitinib treatment in vivo. Our results explored a new mechanism: upregulated CIB2 promoted EMT through ZEB1 to regulate gefitinib resistance, which could be a candidate therapeutic target for overcoming acquired resistance to EGFR-TKIs in NSCLC patients.

Efficacy and Safety of Pioglitazone/Metformin Fixed-Dose Combination Versus Uptitrated Metformin in Patients with Type 2 Diabetes without Adequate Glycemic Control: A Randomized Clinical Trial.

INTRODUCTION: We aim to evaluate the efficacy and safety of pioglitazone/metformin fixed-dose combination (FDC) versus uptitrated metformin in patients with type 2 diabetes mellitus (T2DM) without adequate glycemic control. METHODS: A total of 304 patients were recruited from 15 hospitals in China and randomly assigned (1:1) to the test group (pioglitazone/metformin FDC, 15/500 mg) or the control group (uptitrated metformin, 2000-2500 mg/day). The primary endpoint was the proportion of patients with glycated hemoglobin A1c (HbA1c) ≤ 6.5% and ≤ 7.0% at week 16. The secondary outcomes included the change from baseline in glucose, serum lipids, and liver function. Full analysis set (FAS) and per-protocol set (PPS) were used for analyses. RESULTS: In the test group, 103 (69.59%) patients reached HbA1c ≤ 7.0% (FAS, P = 0.009), with 68 (45.95%) patients achieved HbA1c ≤ 6.5 (FAS, P = 0.043). More reduction in HbA1c, homeostatic model assessment for insulin resistance, and diastolic pressure was found. Bodyweight, body mass index, and high-density lipoprotein cholesterol increased markedly. The changes of triglycerides, alanine transaminase, aspartate aminotransferase, and high-sensitivity C-reactive protein decreased noticeably. There were no significant differences in rates of adverse events between the two groups. CONCLUSIONS: Pioglitazone/metformin FDC was superior to uptitrated metformin among patients with T2DM without adequate glycemic control. TRIAL REGISTRATION NUMBER: This trial is registered with the Chinese Clinical Trial Registry (ChiCTR1900028606).

Prognosis and immunotherapeutic implications of molecular classification of cervical cancer based on immunophenoscore-related genes.

The immunophenoscore (IPS) is an important indicator for evaluating immunotherapy response. This work was designed to establish a prognostic model based on IPS-related genes in cervical cancer. Weighted correlation network analysis (WGCNA) was utilized to identify key modules related to IPS in cervical cancer data from The Cancer Genome Atlas (TCGA). The results show that the yellow module (158 genes) had a high correlation with both IPS_CTLA4_blocker and IPS_CTLA4_and PC1/PDL1/PDL2 blocker. Univariate cox regression analysis and LASSO regression analysis were performed based on 158 genes, and 9 characteristic genes were finally identified to construct the model. According to the differentially expressed genes, cervical cancer samples were divided into high-risk and low-risk groups and cluster 1.2.3. Higher risk scores associated with poorer prognosis. cluster2 and cluster3 were identified as cervical cancer subtypes with significant survival differences. cluster2 had higher immune cell infiltration levels and better prognosis, with greater sensitivity to Cyclopamine, Imatinib, MG-13, Paclitaxel, PHA-665752, Rapamycin, Sorafenib, Sunitinib, and VX-680. In contrast, cluster3 had higher TTN and PIK3CA mutations and greater sensitivity to AZ628, Dasatinib, Doxorubicin, HG-6-64-1, JQ12, Midostaurin, PF-562271, TAE684, and WH-4-023. In conclusion, we developed a feasible risk score model based on IPS-related genes for cervical cancer prognosis and identified potential drugs for different cervical cancer subtypes.

Single-cell mapping of peripheral blood mononuclear cells reveals key transcriptomic changes favoring coronary artery lesion in IVIG-resistant Kawasaki disease.

Background: Intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) poses a considerable challenge to patients and their families due to its severe complications. Previous researches have highlighted the critical role of immune disorders in its pathogenesis. However, fragmented studies based on isolated cases hinder a comprehensive understanding of this deadly illness. This study aimed to explore the overall landscape of peripheral blood mononuclear cells (PBMCs) in IVIG-resistant KD patients using single-cell RNA sequencing (scRNA-seq). Methods: The scRNA-seq was used to characterize the transcriptomic profiles of IVIG-resistant KD patients, IVIG-responsive KD patients, and healthy controls. Data quality control (QC) and subsequent analysis were conducted using various R packages. These included DoubletFinder and Harmony for QC, Seurat and SingleR for identifying and annotating major cell types, ggpubr for calculating and visualizing the percentages of each cell type, Seurat for characterizing differentially expressed genes (DEGs) between groups, pheatmap for visualizing the DEGs, clusterProfiler for performing Gene Ontology (GO) enrichment analysis of DEGs, scRepertoire for TCR and BCR data analysis, Monocle for assessing cell differentiation trajectories, and CellChat for intercellular interaction evaluation. Results: High-quality single-cell transcriptome data from 12 participants were analyzed, including five with IVIG-resistant KD, four with IVIG-responsive KD, and three healthy controls. We identified 10 major cell types and observed that the differentiation of CD8+ effector T cells was impeded in IVIG-resistant KD patients with coronary artery lesion (CAL) according to cell differentiation trajectory analysis. Subsequent cell communication analysis demonstrated that myeloid cluster with high expression of LCN2, S100P, and LTF played a key role, potentially signaling through MIF-CD74/CXCR4 and MIF-CD74/CD44 ligand-receptor pairs. Conclusion: Complex immunopathological changes occur during the development of CAL in IVIG-resistant KD. Stunted differentiation of CD8+ effector T cells is noted in KD-CAL. Interactions between myeloid cells and T cells activates multiple inflammatory signaling pathways, with ligand-receptor pairs, including MIF-CD74/CXCR4 and MIF-CD74/CD44, potentially playing crucial roles.

Influence of Financial Toxicity on the Quality of Life in Lung Cancer Patients Undergoing Immunotherapy: The Mediating Effect of Self-Perceived Burden.

Purpose: The purpose of this study is to understand the level of quality of life (QOL) of lung cancer patients receiving immunotherapy and to clarify the potential mediating role of self-perceived burden (SPB) in the relationship between financial toxicity (FT) and QOL. Patients and Methods: A convenience sample of 342 lung cancer patients receiving immunotherapy was recruited from a cancer hospital from October 2022 to April 2023 for this cross-sectional study. The participants were requested to complete the following structured questionnaires: a sociodemographic and clinical questionnaire, the Functional Assessment of Cancer Therapy-Lung (FACT-L), the Self-Perceived Burden Scale (SPBS) and the COmprehensive Score for Financial Toxicity (COST). The data were subjected to Pearson correlation analysis and bootstrapping analysis in structural equation modelling. Results: The total FACT-L score was 79.90±15.84 points in 322 lung cancer patients receiving immunotherapy. FT (ß = 0.37, P < 0.01) and SPB (ß = -0.27, P < 0.01) had a direct effect on QOL. In addition, SPB partly mediated the association between FT and QOL, and the standardized indirect effect was 0.19, accounting for 33.9% of the total effect. Conclusion: The present study revealed that there is still much room for improvement in the QOL of lung cancer patients during immunotherapy. A greater financial burden resulted in a greater self-perceived burden and was thus associated with inferior QOL. It is imperative for oncology nurses to routinely assess QOL, FT or risk and SPB for lung cancer patients undergoing immunotherapy as well as to assist those patients in understanding the potential financial risk of each choice and help them take more active roles in their routine clinical care.

Transcriptomics Reveals the Mechanism of Platycodin D Targeting TGFß for Anti-Lung Cancer Activity.

Lung cancer is the most prevalent and lethal malignant tumor in China, primarily categorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for more than 80% of all lung cancer cases, with current treatments primarily consisting of surgery, chemotherapy, and targeted therapy. However, these treatments often come with various adverse effects and drug resistance issues, highlighting the urgent need for new NSCLC therapies. Traditional Chinese medicine serves as a natural treasury of medicinal compounds and an important avenue for discovering novel active compounds. Platycodin D (PD) is a triterpenoid saponin isolated from the roots of Platycodon, possessing various pharmacological properties. Nevertheless, the exact mechanism of PD's anti-lung cancer activity remains unclear. In this study, 3 lung cancer cell models, A549, NCI-H1299, and PC-9, were employed. After intervention with Platycodin-D, tumor cell proliferation and migration were assessed. Cell migration ability was assessed through transwell assays, while transcriptomics was employed to explore the mechanism of PD's anticancer activity. Bioinformatic analysis revealed significant enrichment of apoptosis and the TGFß pathway following PD intervention, as shown in gene expression heatmaps, where genes associated with cancer were significantly downregulated by PD intervention. Subsequently, we used immunofluorescent labeling of KI-67 to evaluate cell proliferation, flow cytometry to assess apoptosis, and Western blot to detect protein expression of TGFß and P-SMAD3. Immunofluorescence was also employed to investigate E-cadherin, vimentin, and N-cadherin. Finally, molecular docking and dynamic simulations were utilized to study the interaction between PD and TGFß proteins. The results of this study indicate that PD exhibits robust anti-lung cancer pharmacological activity, with its primary target being TGFß. PD may serve as a potential TGFß inhibitor and a candidate drug for NSCLC treatment.

Proof of Concept of an All-in-One System for Measuring Hepatic Influx, Egress, and Metabolic Clearance Based on the Extended Clearance Concept.

Hepatic clearance (CLH ) prediction is a critical parameter to estimate human dose. However, CLH underpredictions are common, especially for slowly metabolized drugs, and may be attributable to drug properties that pose challenges for conventional in vitro absorption, distribution, metabolism, and elimination (ADME) assays, resulting in nonvalid data, which prevents in vitro to in vivo extrapolation and CLH predictions. Other processes, including hepatocyte and biliary distribution via transporters, can also play significant roles in CLH Recent advances in understanding the interplay of metabolism and drug transport for clearance processes have aided in developing the extended clearance model. In this study, we demonstrate proof of concept of a novel two-step assay enabling the measurement of multiple kinetic parameters from a single experiment in plated human primary hepatocytes with and without transporter and cytochrome P450 inhibitors-the hepatocyte uptake and loss assay (HUpLA). HUpLA accurately predicted the CLH of eight of the nine drugs (within twofold of the observed CLH ). Distribution clearances were within threefold of observed literature values in standard uptake and efflux assays. In comparison, the conventional suspension hepatocyte stability assay poorly predicted the CLH The CLH of only two drugs was predicted within twofold of the observed CLH Therefore, HUpLA is advantageous by enabling the measurement of enzymatic and transport processes concurrently within the same system, alleviating the need for applying scaling factors independently. The use of primary human hepatocytes enables physiologically relevant exploration of transporter-enzyme interplay. Most importantly, HUpLA shows promise as a sensitive measure for low-turnover drugs. Further evaluation across different drug characteristics is needed to demonstrate method robustness. SIGNIFICANCE STATEMENT: The hepatocyte uptake and loss assay involves measuring four commonly derived in vitro hepatic clearance endpoints. Since endpoints are generated within a single test system, it blunts experimental error originating from assays otherwise conducted independently. A key advantage is the concept of removing drug-containing media following intracellular drug loading, enabling the measurement of drug reappearance rate in media as well as the measurement of loss of total drug in the test system unencumbered by background quantities of drug in media otherwise present in a conventional assay.

Furin, ADAM, and γ-secretase: Core regulatory targets in the Notch pathway and the therapeutic potential for breast cancer.

The activation of the Notch pathway promotes the occurrence and progression of breast cancer. The Notch signal plays different roles in different molecular subtypes of breast cancer. In estrogen receptor-positive (ER+) breast cancer, the Notch pathway regulates the activity of estrogen receptors. In human epidermal growth factor receptor 2-positive (HER2+) breast cancer, crosstalk between Notch and HER2 enhances HER2 signal expression. In triple-negative breast cancer (TNBC), Notch pathway activation is closely linked to tumor invasion and drug resistance. This article offers a comprehensive review of the structural domains, biological functions, and key targets of Notch with a specific focus on the roles of Furin protease, ADAM metalloprotease, and γ-secretase in breast cancer and their potential as therapeutic targets. We discuss the functions and mutual regulatory mechanisms of these proteinases in the Notch pathway as well as other potential targets in the Notch pathway, such as the glycosylation process and key transcription factors. This article also introduces new approaches in the treatment of breast cancer, with a special focus on the molecular characteristics and treatment response differences of different subtypes. We propose that the core regulatory molecules of the Notch pathway may become key targets for development of personalized treatment, which may significantly improve treatment outcomes and prognosis for patients with breast cancer.

Evidence of being cured for nasopharyngeal carcinoma: results of a multicenter patient-based study in China.

Background: The survival rates of patients with nasopharyngeal carcinoma (NPC) have improved significantly, but there is no consensus on whether they can be considered cured. We aimed to determine whether a statistical cure could be achieved for patients with NPC in the contemporary therapeutic landscape. Methods: This retrospective multicenter study enrolled 6315 patients with nonmetastatic NPC from nonendemic and endemic regions of China from 2007 to 2020. We applied mixture and nonmixture cure models to estimate the cure probabilities and cure times by incorporating background mortality for the general population, matching by gender, age, and diagnosed year. Findings: With death as the uncured event, the probability of patients with NPC achieving a life expectancy at par with the general population was 78.1%. Considering progression as the uncured event, the likelihood of patients attaining a life expectancy without progression equivalent to that of the general population was 72.4%. For individuals, the probabilities of achieving cure were conditional and time-dependent, requiring approximately 7.1 and 4.7 years with 95% certainty, respectively. The corresponding cure times for uncured patients were 8.9 and 6.8 years, respectively. The cure probability was correlated with age, Eastern Cooperative Oncology Group score, TNM staging, Epstein-Barr virus DNA copies, and lactate dehydrogenase. The correlation was excellent between 5-year overall survival/progression-free survival and cure fractions. Interpretation: Statistical cure is potentially achievable among patients with NPC undergoing contemporary treatment modalities. The results hold significant potential implications for both clinical practice and patient perspectives. Funding: National High Level Hospital Clinical Research Funding; Beijing Xisike Clinical Oncology Research Foundation; Beijing hope run fund.

Trends in research on nanomedicine in urologic cancer: a bibliometric and visualized analysis.

Increasing research efforts are focused on studying the synthesis and mechanisms of nanomedicine in urologic cancer. We performed a bibliometric study of the literature on nanomedicine in urologic cancer over the last 23 years, focusing on aspects such as researchers, institutions, nations, and keywords. We searched for papers in the Web of Science Core Collection from January 1, 2001, to December 29, 2023. Only reviews and original articles written in English were considered. A total of 2386 papers satisfied the given criteria for inclusion. The publications included in the study originated from 90 nations. The United States had the largest number of published papers, accounting for more than 31.01% of the total. The leading institution in this field is the Chinese Academy of Sciences, with a publishing output of 2.35%. Farokhzad, Omid C., is the most prolific author, with 21 articles, and has garnered the most citations, totaling 6271. The latest phrase to enter the top ten most common lists was "gold nanoparticles." We searched for papers in the Web of Science Core Collection from January 1, 2000, to November 28, 2023. Only reviews and original articles written in English were considered. This is the first bibliometric study of nanomedicine in urologic cancer. This article provides a comprehensive analysis of the current state of research on nanomedicine in urologic cancer over the last 23 years. On the basis of this study, future researchers can identify noteworthy publications, journals, and potential collaborators and explore cutting-edge research directions.

High-Throughput SFC-MS/MS Method to Measure EPSA and Predict Human Permeability.

Permeability is a key factor driving the absorption of orally administered drugs. In early discovery, the efficient evaluation of permeability, particularly for compounds violating Lipinski's Rule of 5, remains challenging. Addressing this, we established a high-throughput method to measure the experimental polar surface area (HT-EPSA) as an in vitro surrogate to measure permeability. Compared to earlier methods, HT-EPSA significantly reduces data acquisition time with enhanced sensitivity, selectivity, and data quality. In the effort of translating EPSA to human in vitro and in vivo passive permeability, we demonstrated the application of EPSA for predicting Caco-2 cell and human intestinal permeability, showing improvements over topological polar surface area and the parallel artificial membrane permeability assay for rank-ordering permeability in a proteolysis targeting chimera case study. The HT-EPSA method is expected to be highly beneficial in guiding early stage compound rank-ordering, faster decision-making, and in predicting in vitro and/or in vivo human intestinal permeability.

Hyponatremia Is Associated with Mortality in Acute Pancreatitis Patients.

BACKGROUND: Disorders of serum sodium are common among general patients and are associated with poor outcomes. The prognostic value of serum sodium disorders in patients with acute pancreatitis (AP) has not been studied. We conducted this retrospective study to explore the association between serum sodium levels and the outcomes of patients with AP. MATERIALS AND METHODS: Patients with AP from the Medical Information Mart for Intensive Care III (MIMIC-III) were screened for this study. The laboratory variables, including serum sodium levels, were obtained by analyzing the first blood sample on the first day after admission. Univariate logistic regression was performed to discover potential factors for mortality of AP. The unadjusted and adjusted association between serum sodium level and mortality of AP was shown by the restricted cubic spline (RCS). The categorical cutoff for the detrimental effect of serum sodium level on the prognosis of AP was also confirmed by stepwise logistic regression after adjusting for con-founding effects of significant factors in the univariate logistic regression. RESULTS: A total of 869 patients with AP in the MIMIC-III were included with a mortality of 13.1%. Unadjusted logistic regression showed that age (p < 0.001), simplified acute physiological score (SAPS) (p < 0.001), systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), hemoglobin (p = 0.040), serum creatinine (p = 0.046), and serum phosphorus (p < 0.001) were significantly associated with the mortality of AP. The RCS showed that the serum sodium level was negatively and linearly associated with mortality of AP after adjusting for confounding effects of significant factors in the univariate logistic regression. Serum sodium < 133 mmol/L, which indicated hyponatremia, was significantly correlated with a higher mortality risk than serum sodium ≥ 133 mmol/L (p = 0.013). CONCLUSIONS: Hyponatremia is widely developed among patients with AP and correlates with a higher mortality risk of AP. Physicians should pay more attention to managing patients with AP with hyponatremia.

Risk of Cancer in Patients with Congenital Heart Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: There has been remarkable progress in both diagnosis and treatment of patients with congenital heart disease (CHD), with an increasing number of survivors. Whether patients with CHD are more likely to develop cancer is still a controversial issue. This study aimed to quantitatively estimate the association between patients with CHD and the risk of developing cancer through meta-analysis. METHODS: Web of Science, PubMed, and Embase databases were searched from inception to September 2023 to identify potentially relevant case-control studies and cohort studies that reported risk estimates and confidence intervals (CIs). RevMan software was used to analyze the pooled effect size and test for heterogeneity. The random effect and fixed effect models were applied to the study period. Egger's test was performed to examine publication bias. RESULTS: We analyzed six studies, consisting of 2 case-control studies and 4 cohort studies comprising 276,124 participants. The overall pooled hazard risk for cancer in patients with CHD was 1.71 (95% CI: 1.28-2.28; p < 0.01), with significant heterogeneity (I2 = 97%, p < 0.01). The quantitative analysis of studies indicates that patients with CHD have an increased risk of developing cancer, even after adjusting for chromosomal disorders. CONCLUSION: Our study highlights the importance of controlling modifiable factors in cancer prevention and emphasizes the need for health education for patients with CHD in primary care. Given the limited number of studies included in this analysis, further research is needed to accurately quantify the cancer risk of exposed versus unexposed CHD.

A 23-year bibliometric analysis of the development of global research on hereditary renal carcinoma.

Objectives: Medical research continues to be extensively devoted to investigating the pathogenesis and treatment approaches of hereditary renal cancer. By aspect including researchers, institutions, countries, journals, and keywords, we conduct a bibliometric analysis of the literature pertaining to hereditary renal cancer over the last 23 years. Methods: From the Web of Science Core Collection, we conducted a search for publications published between January 1, 2000 and November 28, 2023. Reviews and original articles were included. Results: A cumulative count of 2,194 publications met the specified criteria for inclusion. The studies of the included articles involved a collective of 2,402 institutions representing 80 countries. Notably, the United States exhibited the highest number of published documents, constituting approximately 45.49% of the total. The preeminent institution in this discipline is the National Cancer Institute (NCI), which maintains a publication volume of 8.98%. In addition to being the most prolific author (125 publications), Linehan WM's works received the highest number of citations (11,985). In a comprehensive count, 803 journals have published related articles. In the top 10 most recent occurrences were the terms "hereditary leiomyomatosis" and "fumarate hydratase." Conclusion: This is the first bibliometric analysis of the literature on hereditary renal cancer. This article offers a thorough examination of the present status of investigations concerning hereditary renal cancer during the previous 23 years.