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

This report presents a case of a 9-year-old child with a complicated crown-root fracture of the maxillary central incisor, accompanied with a root fracture. The treatment strategy was minimally invasive, focusing on vital pulp preservation, root fracture recovery, and crown restoration. The fractured crown was reattached using resin short posts to enhance retention, resulting in aesthetic and functional restoration of the anterior teeth. A 2-year follow-up revealed favorable clinical and radiographic outcomes.
Humans ; Child ; Tooth Fractures/therapy* ; Tooth Root/injuries* ; Incisor/injuries* ; Tooth Crown/injuries* ; Post and Core Technique ; Dental Restoration, Permanent/methods* ; Maxilla

OBJECTIVES: To compare the anti-inflammatory, antibacterial and analgesic effects of Yinqiao Powder (YQS) formulated granules and decoction. METHODS: We first evaluated the anti-inflammatory effects of the two dosage forms of YQS in a LPS-induced RAW 264.7 cell model using RT-qPCR and Western blotting. We further constructed zebrafish models of inflammation by copper sulfate exposure, caudal fin transection, or LPS and Poly (I:C) microinjection, and evaluated anti-inflammatory effects of YQS granules and decoction by examining neutrophil aggregation and HE staining findings. In a mouse model of acute lung injury (ALI) induced by intratracheal LPS instillation, the effects of YQS gavage at 10, 15, and 20 g/kg on lung pathologies were evaluated by calculating lung wet-dry weight ratio and using HE staining, ELISA and Western blotting. The microbroth dilution method was used to evaluate the antibacterial effect of YQS. Mouse pain models established by hot plate and intraperitoneal injection of glacial acetic acid were used to evaluate the analgesic effects of YQS at 10, 15, and 20 g/kg. RESULTS: Both YQS granules and decoction significantly reduced TNF-α, IL-6, and IL-1β expressions and p-STAT3 (Tyr 705) phosphorylation level in LPS-induced RAW 264.7 cells, and obviously inhibited neutrophil aggregation in the zebrafish models. In ALI mice, YQS granules and decoction effectively ameliorated lung injury, lowered lung wet-dry weight ratio, and reduced p-STAT3 (Tyr 705) expression and TNF-α and IL-6 levels. YQS produced obvious antibacterial effect at the doses of 15.63 and 31.25 mg/mL, and significantly reduced body torsion and increased pain threshold in the mouse pain models. CONCLUSIONS The two dosage forms of TQS have similar anti-inflammatory, antibacterial and analgesic effects with only differences in their inhibitory effect on TNF-α, IL-6 and IL-1β mRNA expressions in LPS-induced RAW 264.7 cells.
Animals ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Anti-Inflammatory Agents/pharmacology* ; Analgesics/pharmacology* ; RAW 264.7 Cells ; Zebrafish ; Anti-Bacterial Agents/pharmacology* ; Powders ; Tumor Necrosis Factor-alpha/metabolism* ; Acute Lung Injury/drug therapy* ; Interleukin-6/metabolism* ; Lipopolysaccharides

Chemotherapeutic drugs generally lack specificity, and so the development of a carrier that can actively target delivery of chemotherapy drugs without immunogenicity to organisms has attracted increasing attention. In this work, a multivalent aptamer (Multi-Apt) was constructed by hybridizing a long single-stranded DNA (ssDNA) with tandem repeated sequences synthesized by rolling circle amplification (RCA) with several ssDNA encoding aptamer AS1411 sequences. The double-helix structure was used to load the anti-tumor drug doxorubicin (Dox) for targeted treatment of B16 cells. The binding ratio of RCA product to ssDNA was optimized by agarose gel electrophoresis, and the loading and release of Dox were explored using a microplate reader. The targeting and growth inhibition of Multi-Apt-Dox on B16 cells were investigated by fluorescence microscopy, flow cytometry, microplate reader, CCK-8 assay and wound healing assay. The results showed that the optimal molar ratio of RCA product to ssDNA was 1:50. Fluorescence microscopic pictures, flow cytometry analysis and microplate reader experimental results showed that each Multi-Apt could load approximately 200 Dox molecules, and the affinity of Multi-Apt for B16 cells was 46-fold higher than that of free AS1411. Cell experimental results demonstrated that Multi-Apt induced selective cytotoxicity after intracellular degradation and drug release, thereby greatly reducing the adverse reactions of Dox to normal cells and providing a new strategy for targeted drug delivery in tumor treatment.

OBJECTIVE To study the pharmacokinetic characteristics of ciprofol in pregnant and fetal rats， and provide reference for the application of ciprofol in cesarean section. METHODS Eight pregnant rats were selected. A single dose of 2.4 mg/kg of ciprofol was administered via the tail vein. One fetal rat was selected at 2， 4， 8， 12， 16， 25， 35， 45， 60， and 90 minutes respectively after ciprofol administration. Subsequently， whole blood samples were collected simultaneously from both the pregnant rats and fetal rats. HPLC-MS/MS method was used to determine the concentration of ciprofol in the bodies of pregnant and fetal rats. The ratios of fetal-to-maternal blood concentrations （F/M ratios） at each time point were calculated， and the F/M-time curves were plotted. Subsequently， non-compartmental pharmacokinetic parameters were computed using DAS 2.0 software. RESULTS Compared with pregnant rats， cmax， AUC0-90 min and AUC0-∞ of ciprofol in fetal rats were decreased significantly， while MRT was increased significantly （P＜0.05）. The F/M curve of ciprofol initially increased and then decreased， and between 0.16- 0.84， reaching a maximum value of 0.84 at 45 minutes. CONCLUSIONS Ciprofol can penetrate the placental barrier， and there are significant differences in pharmacokinetic parameters between pregnant and fetal rats. Moreover， the exposure level of ciprofol in fetal rats is much lower than that in pregnant rats. Therefore， ciprofol shows promise as an ideal anesthetic agent for cesarean section delivery.

Objective To develop and validate an evaluation criteria for the clinical utilization of belimumab and to provide a reference for the rationally clinical use of belimumab.Methods Based on the drug instructions of belimumab,reference for rational clinical guidelines,and expert consensus,the drug utilization evaluation criteria for belimumab were established.A retrospective analysis was conducted to assess the rational use of belimumab in inpatients at a hospital in Yunnan Province from January 2021 to June 2024.Results A total of 1 809 medical records were included,involving 213 patients.The rationality rate of belimumab use was 72.5％,with 1 311 cases fully meeting the evaluation criteria.Non-compliance was primarily attributed to medication frequency(15.0％),dosage(9.8％),medication monitoring(4.3％),and efficacy evaluation(3.3％).Conclusions There is a need to enhance the management of dosage,medication monitoring,and efficacy evaluation to further standardize the rational use of belimumab in clinical practice.The drug utilization evaluation criteria established for belimumab are feasible and provide a reference for guiding its rational clinical application.

Objective To identify latent profiles of digital health technophobia among elderly patients with breast cancer and to examine differences in demand for on-line nursing care services.Methods Convenient sampling was used in this cross-sectional study.A total of 350 consecutive perioperative elderly patients with primary breast cancer were recruited from the Departments of General Surgery,affiliated to three Tier-IIIA hospitals in Shijiazhuang from June 2022 to June 2023.Data were collected with a general-information questionnaire,technophobia scale,and demand scale for online appointment nursing service.Results All 348 patients completed the survey.Digital health technophobia in elderly patients with primary breast cancer were categorised into four latent profiles:low technophobia(n=65,18.68%),high technophobia with moderate privacy-security concern(n=96,27.59%),moderate technophobia with high privacy security concern(n=85,24.43%),and high technophobia(n=102,29.31%).There was significant difference in demand for online nursing care services regarding the four latent profiles(F=446.149,P<0.05).Conclusion Elderly patients with breast cancer exhibit four profiles regarding digital health technophobia.It is found that each profile associates with specific demands of online nursing care services.Nursing staff should take tailored interventions to target specific digital health technophobia profiles to meet the demands of online nursing care services among the elderly patients with breast cancer.

Age-related macular degeneration (AMD) seriously endangers the visual health of the elderly, and its incidence rate is on the rise in recent years.As the aging of the population intensifies, the incidence rate of AMD will continue to rise.Therefore, it is crucial to explore its genetic pathogenic mechanism.Genome-wide association studies (GWAS) have identified a large number of single nucleotide polymorphisms associated with AMD.However, most of these polymorphisms are located in noncoding regions, and their functions are unclear.Therefore, revealing the regulatory effects of the genetic variations on gene expression, protein levels, and metabolite abundance serves as a powerful tool for deciphering the functions of noncoding variations discovered in GWAS.Furthermore, combining quantitative trait loci (QTLs) with GWAS can effectively explain GWAS data and increase the likelihood of discovering statistically significant genetic variation loci.This review summarizes research on the analysis and integration of GWAS combined with QTL data, aiming to better understand the impact of gene variations on the occurrence and development of AMD, thereby providing new ideas for searching for effective therapeutic targets for AMD.

Previous studies have reported elevated cardiac troponin T (cTnT) in patients with inclusion body myositis due to skeletal myopathy. Although the trends of cTnT have been reported in some cases, the onset of elevation has barely been reported. In this case, elevated cTnT in a patient diagnosed with inclusion body myositis is discussed. The routine laboratory tests of a 68-year-old male patient showed a positive cTnT test. Eight months later, he developed symptoms of myasthenia gravis. Subsequently, after a series of examinations, the patient was diagnosed with inclusion body myositis. Despite a transient decrease in cTnT levels following intravenous immunoglobulin treatment, the levels rapidly rebounded and continued to rise, suggesting continued progression of skeletal muscle damage in inclusion body myositis. It was concluded that the elevated cTnT was due to re-expression of cTnT in the damaged skeletal muscles of inclusion body myositis. This suggests that dynamic monitoring of cTnT levels in inclusion body myositis patients may predict the progression of myositis and promote timely treatment.

Objective:To investigate the efficacy and safety of ablation index-guided radiofrequency catheter ablation (RFCA) and second-generation cryoballoon ablation (CBA) in elderly patients with atrial fibrillation (AF).Methods:This retrospective cohort study included 1 986 patients undergoing pulmonary vein isolation for AF at General Hospital of Northern Theater Command from August 2016 to May 2020, comprising 760 RFCA cases and 1 226 CBA cases. Elderly patients were defined as those aged 60 years or older, while non-elderly patients were those under 60 years of age. All patients were followed up for 3 years after the procedure to assess AF recurrence rates. Kaplan-Meier survival curves were plotted and compared by log-rank test. Multivariate logistic regression was used to analyze the influencing factors of AF recurrence.Results:Among 1 986 AF patients (aged (58.7±10.2) years; 1 307 males, 65.81%; 987 elderly patients, 49.70%), the overall AF recurrence rate was 24.37% (484/1 986). Kaplan-Meier analysis demonstrated a higher AF recurrence rate in the elderly group compared to the non-elderly group (log-rank P=0.007). In the RFCA group, AF recurrence rate was 22.50% (171/760), with no significant difference between the elderly (24.44%, 88/360) and non-elderly (20.75%, 83/400) subgroups ( P=0.223). In the CBA group, recurrence rates were 25.53% (313/1 226), with significantly higher recurrence in elderly patients (28.55%, 179/627) than non-elderly (22.37%, 134/599) ( P=0.013). Multivariate logistic regression analysis revealed that advanced age was not an independent predictor of AF recurrence ( P=0.447). Longer AF duration and larger left atrial diameter were independent risk factors for recurrence, while male sex was a protective factor (all P<0.05). Conclusion:Pulmonary vein isolation with second-generation CBA and RFCA guided by ablation index are safe and effective in the treatment of AF in elderly patients.