To investigate the risk factors for acute kidney injury (AKI) following the use of amphotericin B deoxycholate and to develop a predictive model to guide clinical monitoring and intervention.

Although cancer immunotherapy has made great strides in the clinic, it is still hindered by the tumor immunosuppressive microenvironment (TIME). The stimulator of interferon genes (STING) pathway which can modulate TIME effectively has emerged as a promising therapeutic recently. However, the delivery of most STING agonists, specifically cyclic dinucleotides (CDNs), is performed intratumorally due to their insufficient pharmacological properties, such as weak permeability across cell membranes and vulnerability to nuclease degradation. To expand the clinical applicability of CDNs, a novel pH-sensitive polycationic polymer-modified lipid nanoparticle (LNP-B) system was developed for intravenous delivery of CDNs. LNP-B significantly extended the circulation of CDNs and enhanced the accumulation of CDNs within the tumor, spleen, and tumor-draining lymph nodes compared with free CDNs thereby triggering the STING pathway of dendritic cells and repolarizing pro-tumor macrophages. These events subsequently gave rise to potent anti-tumor immune reactions and substantial inhibition of tumors in CT26 colon cancer-bearing mouse models. In addition, due to the acid-sensitive property of the polycationic polymer, the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP (LNP-D). These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy.

Cold tumors have a poor response to tumor immunotherapy due to low immune cell infiltration and the ability to evade immune attacks. Converting cold tumors into hot tumors can enhance the clinical effectiveness of anti-tumor immunotherapy. High-intensity focused ultrasound (HIFU) as a non-invasive treatment can damage tumors through mechanical effects, but there is a lack of research on its cytotoxic mechanisms at the cellular level and its role in inducing anti-immune responses. In this study, the role of HIFU in triggering tumor ferroptosis by disrupting the GSH/GSSG balance through mechanochemical action and the associated anti-tumor immune priming effect were investigated. The use of a nano-enhancer loaded with PFOB combined with HIFU could enhance ferroptosis in triple-negative breast cancer at a specific stage of tumor growth (UTGR = 0) while promoting the conversion of a cold tumor into a hot tumor, thereby improving the immune response. Overall, this provides valuable guidance for the clinical application of HIFU in tumor immunotherapy.

Objective:To construct an evidence-based practice program for dietary management of patients with non-dialysis chronic kidney disease (CKD) based on best evidence and to evaluate the effectiveness of its application.Methods:The best evidence for dietary management of non-dialysis CKD patients was summarized. From September to October 2022, following the evidence clinical transformation model of the Fudan University Centre for Evidence-based Nursing, the best evidence was screened and evidence-based practice program were developed, taking into account patients' wishes, expert opinions, and clinical contexts. From November 2022 through March 2023, baseline reviews, analysis of barriers and facilitators were implemented. Between April 2023 and April 2024, evidence-based practice was carried out in the Department of Nephrology of the Second Affiliated Hospital of Guangzhou Medical University to compare the implementation rate of review indicators at the system, practitioner, and patient levels, and practitioners' knowledge before and after the application of evidence.Results:A total of 14 review indicators were developed. The implementation rate of the 12 review indicators and the practitioners' knowledge of the CKD diet were elevated after the evidence-based practice ( P<0.05) . Conclusions:Evidence-based practice program for dietary management of patients with non-dialysis CKD has a positive effect on improving practitioners' knowledge of non-dialysis CKD diets, implementation rate of dietary management behaviors, and patients' dietary behaviors.

Objective To determine the effect of non-high-density lipoprotein cholesterol(non-HDL-C)on all-cause and cause-specific mortality in an ≥60-year-old elderly population.Methods A total of 16 642 older adults(≥60 years)were subjected from the National Health and Nutrition Examination Survey between 1999 and 2018.According to the tertile of non-HDL-C level,the par-ticipants were divided into tertile 1(＜3.15 mmol/L,n=5499),tertile 2(3.15-4.06 mmol/L,n=5499),and tertile 3 groups(＞4.06 mmol/L,n=5644).The occurrences of all-cause,cardiovascu-lar,and non-cardiovascular death were identified as the study endpoint.Cox proportional hazards regression,Kaplan-Meier survival and restricted cubic spline curve analyses were applied for sta-tistical study.Results An obvious L-shaped associations were observed in non-HDL-C level with risks for all-cause,cardiovascular,and non-cardiovascular death.After adjusting multivariable,the tertile 1 group had significantly higher risks for all-cause,cardiovascular,and non-cardiovascular death than the tertile 2 group(HR=1.123,95％CI:1.054-1.200,P=0.000;HR=1.142,95％CI:1.024-1.292,P=0.027;HR=1.113,95％CI:1.033-1.210,P=0.011).Kaplan-Meier survival analysis showed that the tertile 1 group had notably lower survival rate than the tertile 2 group and the tertile 3 group(P＜0.01).Threshold effect analysis revealed that when non-HDL-C level was lower than 3.36,3.18 and 3.59 mmol/L,respectively,the risk of all-cause,cardiovascular,and noncardiovascular mortality was increased.Conclusion In the elderly ≥60-year-old population,non-HDL-C level exhibited a L-shaped association with all-cause and cause-specific mortality,and＞3.18 mmol/L is regarded as a rational range.

Rescue vehicles and nursing unit drug stock are important in the clinical rescue process.Strengthening the management of rescue vehicles and nursing unit drug stock is conducive to ensuring the safety of clinical medication and impro-ving the quality of medical services.Based on scientificity,universality,guidance,and operability principles,the standard prepa-ration team revealed relevant national policy documents,domestic and foreign standards specifications,and literature.It sorted the key contents of rescue vehicles and base drug management.After several rounds of opinion collection and expert argumentation,the social organization standard Pharmacy administration and pharmacy practice in healthcare institutions—Part 3-7-3:Pharma-ceutical supply services—Key drugs management—Rescue vehicle and nursing unit drug stock management was proved.The main content of the standard includes 10 elements from 3 key parts:basic requirements,management processes,and quality manage-ment and evaluation improvement,to provide guidance in allocating,storing,and managing rescue vehicles and nursing unit drug stock.

Objective:To analyze the clinical features of pachydermoperiostosis (PDP) and improve its diagnostic level.Methods:A retrospective analysis was conducted on the clinical data of four patients with PDP treated at Sun Yat-sen Memorial Hospital, Sun Yat-sen University from 2015 to 2023, including clinical manifestations, laboratory tests, imaging examinations, and genetic testing results.Results:All four patients were male with an average onset age of 15 years old (ranging from 9 to 18 years old). One patient′s uncle had PDP, and another patient′s parents were consanguineous, though neither parent showed signs of PDP. All four patients exhibited clubbing, skin thickening, and acne; three had frontal bossing and deepened nasolabial folds; two showed scalp sulci changes on head MRI, and all had periosteal thickening of the phalanges visible on X-ray. One patient accompanied with hypokalemic nephropathy, and another had gastric ulcer. One patient underwent whole exome sequencing test which revealed a homozygous mutation, SLCO2A1 gene c.1406C>T, leading to a protein change p.Pro469Leu. Computational tools REVEL, SIFT, and Polyphen2 predicted this variant as deleterious.Conclusion:In addition to skin thickening, frontal bossing, scalp sulci changes, clubbing, and periosteal proliferation, patients with PDP may also present with hypokalemic nephropathy and gastric ulcer. The SLCO2A1 gene c.1406C>T mutation may be pathogenic.

T cell response plays an important role in anti-viral infection and anti-tumor immunity,and antigen-specific T cell detection is essential for study of T cell response.This article reviews progress of antigen-specific T cell detection technology,including enzyme-linked immunospot(ELISPOT)assay,intracellular cytokine staining(ICS)assay and activation-induced labeling(AIM)assay,which based on detection of cytokine secretion or activation phenotypes of specific T cells after stimulation and reactivation with antigen in vitro.Another class of methods include Tetramer technology based on known epitopes-human leukocyte antigen(HLA)restriction and recently developed single-cell transcriptomes and T-cell antigen receptor(TCR)sequencing technology.Application of the above methods has advanced our understanding of antigen specific T cell response:Strength and duration of the response,subpop-ulation information,epitopes and their associated HLA-restriction,TCR cloning information and transcriptome characteristic.

BACKGROUND: Renal osteodystrophy (ROD) is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder (CKD-MBD) that is characterized by aberrant bone mineralization and remodeling. ROD increases the risk of fracture and mortality in CKD patients. The underlying mechanisms of ROD remain elusive, partially due to the absence of an appropriate animal model. To address this gap, we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing (RNA-seq). METHODS: Eight-week-old male C57BL/6J mice were randomly allocated into three groups: control group ( n = 5), adenine and high-phosphate (HP) diet group ( n = 20), and the optimized adenine-containing diet group ( n = 20) for 12 weeks. We assessed the skeletal characteristics of model mice through blood biochemistry, microcomputed tomography (micro-CT), and bone histomorphometry. RNA-seq was utilized to profile gene expression changes of ROD. We elucidated the functions of differentially expressed genes (DEGs) using gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). DEGs were validated via quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: By the fifth week, adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group, precluding further model development. Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels, accompanied by pronounced hyperparathyroidism and hyperphosphatemia. The femur bone mineral density (BMD) of the model mice was lower than that of control mice, with substantial bone loss and cortical porosity. ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers. Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice. Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway. The significant upregulation of alkaline ceramidase 1 ( Acer1 ), alkaline ceramidase 2 ( Acer2 ), prosaposin-like 1 ( Psapl1 ), adenosine A1 receptor ( Adora1 ), and sphingosine-1-phosphate receptor 5 ( S1pr5 ) were successfully validated in mouse femurs by qRT-PCR. CONCLUSIONS Optimized adenine diet mouse model may be a valuable proxy for studying ROD. RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis, thereby providing new avenues for therapeutic intervention.
Animals ; Mice ; Chronic Kidney Disease-Mineral and Bone Disorder/genetics* ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Sphingolipids/metabolism* ; Transcriptome/genetics* ; Signal Transduction/genetics* ; X-Ray Microtomography ; Adenine