Objective: To investigate the association between uric acid level and elevated blood pressure among children and adolescents in Guangzhou, so as to provide a scientific basis for prevention and control of hypertension in the pediatric population. Methods: From March to December 2019, using stratified cluster random sampling, 3 626 children and adolescents aged 6-17 years without elevated blood pressure at baseline were recruited from 6 primary and secondary schools in Guangzhou. Serum uric acid levels were measured at baseline, and divided into four groups ( Q1-Q 4) based on age and sex specific quartiles for analyses. Two waves of follow up were carried out from October 2020 to May 2021 and from October 2021 to May 2022, respectively. Multilevel robust Poisson regression was used to evaluate the association between uric acid level and elevated blood pressure among children and adolescents. The additive interaction between high uric acid level and sugar sweetened beverage (SSB) intake on elevated blood pressure was assessed by stratification analysis and calculation of the relative excess risk due to interaction (RERI). Results: A total of 1 131 new cases of elevated blood pressure were identified during the two follow ups, with an incidence density of 130.5 cases 1 000 person years. Multilevel robust Poisson regression analysis showed that after adjusting for confounders such as gender, age and annual family income, compared with those in the uric acid Q 1 level, the risk of elevated blood pressure in individuals in the Q 4 level increased by 25% ( RR=1.25, 95%CI =1.08-1.44), and the risk of elevated systolic blood pressure increased by 20% ( RR=1.20, 95%CI =1.05-1.36) (both P <0.05); no statistical association was observed between uric acid and elevated diastolic blood pressure (all P >0.05). In the stratified analysis, the statistical associations of uric acid Q 4 level with elevated blood pressure ( RR=1.34, 95%CI =1.13-1.58) and elevated systolic blood pressure ( RR=1.33, 95%CI =1.14-1.55) were only observed in the group with SSB intake ≥ 250 mL/week (both P <0.05). The RERI values for the effect of uric acid Q 4 and Q 3 levels with SSB intake ≥ 250 mL/week on elevated systolic and diastolic blood pressure were 0.29 and 0.44 (both P <0.05). Conclusions High uric acid level is a risk factor for elevated blood pressure among children and adolescents, with a predominant effect on systolic blood pressure. High uric acid level and SSB intake synergistically promote the increase of blood pressure of children and adolescents.

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.

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.

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

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.

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

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

Objective To investigate the association between cystatin C level and 6-month mortali-ty as well as re-hospitalization in elderly patients with heart failure(HF).Methods The clinical data in this study were from a retrospective cohort study,Zigong Heart Failure Study.A total of 1786 elderly HF patients admitted in Zigong Fourth People's Hospital from December 2016 to June 2019 were selected.According to the tertiles of cystatin C level,the subjected patients were divided into three groups,with the cystatin C level of 1.10±0.17(587 cases),1.60±0.17(599 ca-ses),and 2.91±0.90 mg/L(600 cases),respectively.The primary endpoint was a composite end-point of death at 6 months after discharge and readmission due to HF.Multivariate Cox propor-tional hazards regression analysis was employed to analyze the relationship of the cystatin C level with the composite endpoint of 6-month mortality and readmission due to HF.Restricted cubic spline was used to model the relationship between the cystatin C level and the composite end-point,Kaplan-Meier survival curve was plotted to analyze the differences in 6-month event free survival rates among the three groups,and ROC curve was drawn to analyze the predictive value of cystatin C level for the composite endpoint.Results Multivariate Cox proportional hazards re-gression analysis showed that the middle and upper tertiles of cystatin C level were risk factors for the composite endpoint of 6-month mortality and readmission due to HF(HR=1.170,95％CI:0.970-1.390,P=0.111;HR=1.452,95％CI:1.190-1.756,P=0.000).When taking cystatin C level as a continuous variable,the results remained consistent:for every one standard deviation increase in cystatin C level,HR=1.141,95％CI:1.060-1.226 in Model 3;For every 1 mg/L in-crease,HR=1.152,95％CI:1.057-1.250 in Model 3.Restricted cubic spline displayed a non-linear inverse J-shaped relationship between cystatin C level and the composite endpoint of 6-month mortality and readmission due to HF,with a risk inflection point of cystatin C level at 2.13 mg/L.ROC curve analysis showed that the AUC value of cystatin C level in predicting the composite endpoint,6-month death and re-admission due to HF was 0.572,0.667 and 0.554,respectively.Conclusion Elevated cystatin C level is independently associated with an increased risk of the composite endpoint of 6-month death and re-admission in elderly HF patients.

Objective To investigate the effects of scribble planar cell polarity protein(SCRIB)on proliferation,apoptosis,and autophagy of glioblastoma(GBM)and elucidate its potential underlying mechanisms.Methods The expression level of SCRIB in GBM tissue was queried through the Biomarker Exploration of Solid Tumors(BEST)database.Lentivirus-mediated shRNA interference was employed to downregulate SCRIB expression in human glioblastoma cell lines U87 and U251,which were divided into negative control group(mock)and SCRIB shRNA interference groups(kd1 and kd2).SCRIB expression levels were detected using Western blotting(WB)and quantitative polymerase chain reaction(qPCR).EdU incorporation and cell apoptosis rates were detected by flow cytometry(FCM).CCK-8 assay was used to detect the proliferation vitality of U87 and U251 cells,and WB was used to detect the expression of proliferation-related proteins.Immunofluorescence(IF)staining was conducted to detect the expression of autophagy-related proteins LC3 and p62,followed by quantitative analysis across multiple fields.WB was also used to detect the expression levels of LC3,p62,and proteins in the JAK-STAT3 signaling pathway.Results Compared with that of normal tissues,SCRIB mRNA expression level was significantly upregulated in GBM tissues(P＜0.05).FCM results showed that EdU incorporation rates were significantly reduced(P＜0.001)while cell apoptosis rates were markedly increased(P＜0.001)in U87 and U251 cells with SCRIB knockdown.CCK-8 results indicated that compared with the mock group,the proliferation vitality of U87 and U251 cells in the SCRIB knockdown group was significantly downregulated(P＜0.001).IF staining showed that LC3 fluorescence aggregation was significantly enhanced(P＜0.001),while p62 fluorescence aggregation was significantly reduced(P＜0.001)in the SCRIB knockdown group.WB results showed that compared with the mock group,the protein expression levels of p27,LC3,p-JAK2 and p-STAT3 were upregulated,while C-Myc,Cyclin D1,MCM,PCNA and p62 were downregulated,with statistically significant differences(P＜0.05).Conclusion Downregulation of SCRIB may induce autophagy and apoptosis in glioblastoma cells by inhibiting the JAK-STAT3 signaling pathway,thereby suppressing cell proliferation.

Objective To investigate the association of neutrophil-to-lymphocyte ratio(NLR)with all-cause and cause-specific mortality in elderly hypertensive patients.Methods In this cohort study,9939 elderly hypertensive patients were enrolled from the National Health and Nutrition Examination Survey between 1999 and 2018.According to the quartile of NLR,the participants were divided into Q1(n=2461),Q2(n=2460),Q3(n=2522)and Q4(n=2496)groups.Their survival status was determined based on National Death Index records.Cox proportional risk regression model,restricted cubic spline curve,Kaplan-Meier survival analysis and ROC analysis were performed.Results After adjusting for confounding factors,Cox proportional risk regression analysis showed a progressive increase in all-cause and cause-specific mortality across quartiles of NLR in elderly hypertensive patients.Compared with the Q1 group,the Q4 group had higher risks for all-cause mortality(HR=1.52,95％CI:1.32-1.74,P=0.000),cardiovascular mortality(HR=2.04,95％CI:1.63-2.56,P=0.000),and non-cardiovascular mortality(HR=1.30,95％CI:1.11-1.53,P=0.000)after adjustment.Restricted cubic spline curve analysis indicated that NLR was positively correlated with all-cause mortality,cardiovacular mortality and non-cardio-vascular mortality.More pronounced association between NLR and cardiovascular death was observed in patients not taking statins(P=0.035).ROC analysis revealed that the AUC value of NLR in predicting all-cause mortality,cardiovascular mortality and non-cardiovascular mortality was 0.612,0.597 and 0.581,respectively,showing better performance than high-sensitivity C-reac-tive protein and neutrophils.Conclusion Elevated NLR level is independently associated with increased risks of all-cause and cause-specific mortality in elderly hypertensive patients.In the patients not taking statins,a stronger association is observed between NLR and cardiovascular mortality.