OBJECTIVE To assess the correlation between the steady-state minimal concentration （cmin） and 24 h area under the drug concentration-time curve （AUC24）/minimal inhibitory concentration （MIC） ratio （AUC24/MIC） of vancomycin in pediatric patients， and analyze independent risk factors for treatment failure. METHODS Data of hospitalized children treated with vancomycin and receiving therapeutic drug monitoring in our hospital from January 2021 to July 2024 were retrospectively collected and divided into success group and failure group according to whether the treatment was successful or not. Spearman correlation analysis was used to analyze the correlation between cmin and AUC24/MIC of vancomycin， and one-way and multifactorial Logistic regression analyses were used to screen the independent risk factors for vancomycin treatment failure. RESULTS A total of 59 children were included， with 41 in the success group and 18 in the failure group. Compared with the failure group， AUC24/MIC of vancomycin was significantly higher in the success group （P＝0.038）， but there was no statistically significant difference in the cmin of the two groups （P＞0.05）； cmin of vancomycin was significantly positively correlated with AUC24/MIC （r＝0.499， P＜0.001）， but it has a certain efficacy in predicting the achievement of the AUC24/MIC standard （≥400） （area under the receiver operator characteristic curve＝0.696）， with an optimal cutoff value of 6.05 mg/L determined by the Youden index. The efficacy of AUC24/ MIC in predicting treatment failure was superior to cmin （areas under the receiver operator characteristic curve were 0.671 vs. 0.523， P were 0.038 vs. 0.684）， with higher sensitivity （83.3% vs. 66.7%）. Hypoproteinemia and AUC24/MIC≤369.1 were independent risk factors for vancomycin treatment failure （P＜0.05）. The incidence of nephrotoxicity was 3.4%. CONCLUSIONS There is a significant positive correlation between cmin and AUC24/MIC of vancomycin in pediatric patients； hypoproteinemia and AUC24/MIC≤369.1 are independent risk factors for vancomycin treatment failure in children.

Objective: To analyze the epidemiological characteristics of leptospirosis in Jinhua City, Zhejiang Province, from 2007 to 2024, so as to provide a basis for improving the prevention and control strategies of leptospirosis. Methods: Data pertaining to leptospirosis cases in Jinhua City from 2007 to 2024 were collected through the Monitoring and Reporting Management System of the Chinese Disease Prevention and Control Information System. Descriptive epidemiological methods were used to analyze the distribution characteristics of leptospirosis in terms of time, region, population, interval from the onset of the disease to diagnosis and the outbreak of the epidemic. Results: A total of 81 cases of leptospirosis were reported in Jinhua City from 2007 to 2024, with an average annual reported incidence of 0.08/100 000. The peak incidence occurred from August to September, with 57 cases accounting for 70.37%. Leptospirosis cases were reported in 9 counties (cities, districts) in Jinhua City. Pan'an County reported the most cases, with 52 cases accounting for 64.20%. There were 54 male cases and 27 female cases, with a male-to-female ratio of 2∶1. The majority of cases were aged over 40 years, with 73 cases accounting for 90.12%. The average reported incidence of leptospirosis showed an upward trend with the increase of age (P<0.05), and the highest incidence of leptospirosis was at the 60-<80 age group (0.21/100 000). The majority of patients were farmers, with 77 cases accounting for 95.06%. The median interval from onset to diagnosis was 4.00 (interquartile range, 6.00) days. There were significant differences in the interval from onset to diagnosis among cases in Dongyang City compared with Pan'an County, Wuyi County, and Wucheng District, between Pan'an County and Jindong District, Wucheng District, and between Wuyi County and Wucheng District (all P<0.05). In 2007, one outbreak of leptospirosis was reported, which occurred in Jiuhe Township, Pan'an County, with 36 reported cases. Conclusions The reported incidence of leptospirosis in Jinhua City from 2007 to 2024 is generally low. The high-incidence period is from August to September, and Pan'an County is the high-incidence area. Males over 40 years and farmers are the key populations for prevention and control. It is recommended to strengthen epidemic surveillance and health education for high-risk populations.

Objective: To investigate the value of the Chinese visceral adiposity index (CVAI) in predicting hypertension risk, so as to provide a tool for the early assessment of hypertension risk. Methods: Health examination individuals aged ≥18 years were selected from four medical institutes in Jinhua City, Zhejiang Province in 2022. Data on basic information, lifestyle, disease history, body mass index, waist circumference, blood pressure, and blood biochemical indicators were collected through questionnaire surveys and physical examinations. CVAI was calculated to assess levels of visceral fat accumulation, divided by quartiles into Q1, Q2, Q3, and Q4 groups. The relationship between CVAI and hypertension was analyzed using a multivariable logistic regression model, and their dose-response relationship was examined using a restricted cubic spline model. The value of CVAI in predicting hypertension risk was evaluated using receiver operating characteristic (ROC) curve. Results: A total of 23 791 individuals were enrolled, with a median age of 68.00 (interquartile range, 14.00) years. Among them, 10 178 (42.78%) were males and 13 613 (57.22%) were females. The median CVAI was 111.40 (interquartile range, 48.23). Hypertension was identified in 15 563 cases, with a prevalence of 65.42%. After adjusting for lifestyle, disease history, and blood biochemical indicators, the multivariable logistic regression analysis revealed that hypertension risk in the CVAI Q2, Q3, and Q4 groups were 2.012 (95%CI: 1.865-2.170), 3.059 (95%CI: 2.826-3.311), and 5.099 (95%CI: 4.672-5.565) times that of the Q1 group, respectively. The restricted cubic spline model revealed a non-linear relationship between CVAI and hypertension risk (Pnon linearity<0.05). Hypertension risk increased more rapidly when the CVAI was ≥81.03. The area under the ROC curve for CVAI in predicting hypertension risk was 0.691, with an optimal cutoff value of 106.01, which falls within the Q2 group. Conclusions There was a nonlinear dose-response relationship between CVAI and hypertension. CVAI can predict the risk of hypertension, and 106.01 can serve as an early warning threshold for risk screening.

Indwelling urinary catheterization is one of the most widely used invasive procedures in clinical practice, playing a critical role in disease diagnosis, treatment, and monitoring. In 2024, the European Association of Urology Nurses (EAUN) released the Best Practice Guidelines for Indwelling Urinary Catheterization in Adults-Transurethral and Suprapubic Catheterization (hereinafter referred to as the Guideline), aiming to provide evidence-based clinical guidance and health education information for healthcare professionals. This article interprets the section on "Nursing Principles" within the Guideline, which spans the entire process of catheter management. Key aspects covered include pre-insertion preparation, catheter insertion procedure, catheter maintenance and securement, observation of urine color, prevention of constipation, and catheter removal. The aim is to help urology nurses and related healthcare personnel gain an in-depth understanding of the recommendations in the Guideline, promote its standardized application in clinical practice, improve the quality of indwelling catheter care, and ensure patient safety.

OBJECTIVES: To explore the therapeutic mechanism of compound Centella asiatica formula (CCA) for alleviating Schistosoma japonicum (Sj)-induced liver fibrosis in mice. METHODS: The active components and targets of CCA were identified using the TCMSP database with cross-analysis of Sj-related liver fibrosis targets. A "drug-component-target-pathway-disease" network was constructed using Cytoscape 3.9.1. Functional enrichment analysis (GO/KEGG) was performed using DAVID. Molecular docking study was carried out to validate interactions between the core targets and the key compounds. For experimental validation of the results, 36 mice were divided into control group, Sj-infected model group, and CCA-treated groups. In the latter two groups, liver fibrosis was induced via abdominal infection with Sj cercariae for 8 weeks, followed by 8 weeks of daily treatment with CCA decoction or saline. Hepatic pathology of the mice was assessedwith HE and Masson staining, and hepatic expressions of collagen-I and collagen-III were detected using immunohistochemistry; serum IL-6 and TNF-α levels were determined with ELISA. Hepatic expressions of TLR4 and MyD88 proteins were analyzed with Western blotting. RESULTS: We identified a total of 107 bioactive CCA components and 791 targets, including 37 intersection targets linked to Sj-induced fibrosis. The core targets included TNF, TP53, JUN, MMP9, and CXCL8, involving the IL-17 signaling, lipid metabolism, TLR4/MyD88 axis, and cancer pathways. Molecular docking study confirmed strong binding affinity between quercetin (a primary CCA component) and TNF/TP53/JUN/MMP9. In Sj-infected mouse models, CCA treatment significantly attenuated hepatic inflammatory cell infiltration, reduced collagen-I and collagen-III deposition, improved tissue architecture, reduced serum IL-6 and TNF-α levels, and downregulated TLR4 and MyD88 expressions in the liver. CONCLUSIONS CCA mitigates Sj-induced liver fibrosis by targeting TNF, TP53, JUN, and MMP9 to modulate the TLR4/MyD88 pathway, thereby suppressing pro-inflammatory cytokine release, inhibiting hepatic stellate cell activation, reducing collagen deposition, and preventing granuloma formation in the liver.
Animals ; Toll-Like Receptor 4/metabolism* ; Mice ; Myeloid Differentiation Factor 88/metabolism* ; Schistosoma japonicum ; Liver Cirrhosis/parasitology* ; Schistosomiasis japonica ; Signal Transduction ; Molecular Docking Simulation ; Inflammation ; Centella/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

OBJECTIVES: To assess the effectiveness of the comparison between pit and fissure sealants and fluoride varnishes, as well as various types of sealants, in preventing caries on the occlusal surface of children's first permanent molars (FPM). METHODS: Conduct a comprehensive search of literature published between January 1, 1988, and May 30, 2024, in the following databases: China National Knowledge Infrastructure, Web of Science, Cochrane Library, Embase, PubMed, China Science Periodical Database and China Biology Medicine database. Meta-analysis and subgroup analyses were performed on the literature that met the inclusion criteria. RESULTS: A total of 5 618 pieces of literature were retrieved, resulting in the inclusion of 14 in the study. Meta-analysis showed that there was no statistically significant difference in the efficacy between varies pit and fissure sealants compared to fluoride varnishes, and between varies types of sealants in preventing caries on the occlusal surface of children's first permanent molars within 24 months post-surgery (P>0.05). CONCLUSIONS Within 24 months, there was no significant difference in the effectiveness of using resin-based or glass iomomer pit and fissure sealants compared with fluoride varnishes in preventing occlusal caries in FPM in children; within 24 months, there was no significant difference in the effectiveness of using resin-based sealants compared with ART sealants in preventing occlusal caries in FPM in children. ART sealants are recommended over resin-based sealers for children who have no conditions for chair-side manipulation or who are poorly co-operative.
Humans ; Pit and Fissure Sealants/therapeutic use* ; Dental Caries/prevention & control* ; Molar ; Child ; Fluorides, Topical/therapeutic use* ; Dentition, Permanent

The treatment process of multiple fertilization failure and salvage fertilization in a male infertile patient was retrospectively analyzed. The patient underwent in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in another hospital for 3 cycles, all of which had fertilization abnormalities. The complex heterozygous mutation of PLCZ1 gene was detected by infertility gene paneland confirmed by Sanger sequencing in the Reproductive Medicine Center of Renmin Hospital, Hubei University of Medicine, and the gene mutation was derived from both parents. No abnormal mutations were found in the woman's genetic testing. The woman underwent progestin-primed ovarian stimulation, resulting in the retrieval of 9 oocytes. ICSI combined with 10 μmol/L ionomycin assisted oocyte activation (AOA) was applied to all mature eggs,resulting in 7 normal fertilized oocytes and 7 cleavage embryos, 2 high-quality cleavage embryos were frozen. Two months later, the woman underwent frozen-thawed embryo transfer to obtain biochemical pregnancy. Simultaneously, we reviewed the literature on PLCZ1 gene mutations and AOA related literature at home and abroad. From this case we can draw the following conclusions: 1) When no fertilization or polyspermia occurs in an IVF cycle and total fertilization fails in ICSI, genetic testing of both spouses is required to find genetic factors. 2) The mutation of PLCZ1 gene mainly leads to fertilization failure. ICSI combined with AOA is an effective method to rescue fertilization failure. Ionomycin has a significant effect on oocyte activation, and has no effect on embryo formation. However, we still need to accumulate case data to verify the safety of ionomycin AOA.

BACKGROUND:Cognitive impairment is the most common complication after stroke,and its severity is closely related to the patient's prognosis.The prognosis of patients can be significantly improved if the severity of their cognitive impairment is recognized and targeted early.OBJECTIVE:To initially explore potential biomarkers affecting the progression of post-stroke cognitive impairment,thereby providing a richer and unique reference for the study of their pathophysiological mechanisms.METHODS:Using ultra performance liquid chromatography-mass spectrometry,non-targeted metabolomics analysis was conducted on serum samples from patients with mild and moderate post-stroke cognitive impairment to identify differential metabolites between the two groups.To further validate the diagnostic efficacy of the differential metabolites,the receiver operating characteristic curve analysis was used to evaluate their accuracy and sensitivity in distinguishing disease severity.In addition,pathway analysis was conducted on the differential metabolites.RESULTS AND CONCLUSION:(1)There were significant differences in metabolic profiles between patients with mild and moderate post-stroke cognitive impairment,and 9 differential metabolites were screened by the receiver operating characteristic curve.(2)Differential metabolite pathway analysis revealed that the metabolic pathways affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment included tryptophan metabolism,D-amino acid metabolism,biotin metabolism,retinol metabolism,aminoacyl-tRNA biosynthesis,lysine degradation,protein digestion and uptake,pyrimidine metabolism,cysteine and methionine metabolism,ABC transporter proteins,amino acid biosynthesis,and 2-oxocarboxylic acid metabolism.To conclude,9 potential biomarkers affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment have been identified,involving 12 metabolic pathways including tryptophan metabolism,D-amino acid metabolism and retinol metabolism.

Objective To investigate the association between butyrate metabolism-related genes(BMRGs)and the prognosis of lung adenocarcinoma(LUAD),construct a prognostic model,and evaluate its predictive value.Methods Differentially expressed BMRGs(BMR-DEGs)were screened from the TCGA-LUAD dataset.Cox and LASSO regression analyses were employed to establish a risk scoring model,stratifying patients into low-and high-risk groups.The model's performance was assessed using Kaplan-Meier(K-M)and receiver operating characteristic(ROC)curves,with external validation conducted using the GSE68465 dataset.In vitro experiments included RT-PCR and Western blotting to measure insulin-like growth factor binding protein 1(IGFBP1)expression.IGFBP1 was knocked down using siRNA,and its effects on cell proliferation,migration,and invasion were evaluated via CCK-8,colony formation,Transwell,and wound healing assays.Gene Set Enrichment Analysis(GSEA)was performed to explore IGFBP1-related regulatory mechanisms.Results We identified a total of 51 BMR-DEGs,primarily involved in biological processes such as cell proliferation,migration,and invasion,and associated with the PI3K-Akt and MAPK signaling pathways.The constructed 5-gene risk scoring model demonstrated that high-risk patients had significantly worse overall survival(OS)than low-risk patients(P＜0.05).IGFBP1 was highly expressed in LUAD tissues and correlated with poor prognosis.Knockdown of IGFBP1 significantly suppressed cancer cell proliferation,migration,and invasion(P＜0.05).GSEA revealed that IGFBP1 was linked to lipid metabolism-related pathways.Conclusion BMRGs are associated with LUAD prognosis,and the established risk scoring model exhibits strong predictive performance.High IGFBP1 expression correlates with unfavorable outcomes,and its knockdown inhibits cancer cell proliferation,migration,and invasion.