ObjectiveTo investigate the uric acid-lowering effects and mechanisms of acacetin on hyperuricemia （HUA） in mice. MethodsOteracil potassium and adenine were used to establish the mouse model of HUA. Male Kunming mice （n=48） were randomized into six groups： control， model， low-dose （12.5 mg·kg^-1） acacetin， medium-dose （25 mg·kg^-1） acacetin， high-dose （50 mg·kg^-1） acacetin， and allopurinol （10 mg·kg^-1）. Each group received continuous gavage administration for 21 days. An automatic biochemical analyzer was used to measure the levels of uric acid （UA）， creatinine （Cr）， urea nitrogen （BUN）， alanine aminotransferase （ALT） and aspartate aminotransferase （AST）. Additionally， the activity of xanthine oxidase （XOD） in the liver and the levels of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and IL-18 in the serum were measured by enzyme-linked immunosorbent assay （ELISA）. Pathological changes in the renal tissue were observed by hematoxylin-eosin （HE） staining. Western blot was employed to determine the levels of glucose transporter 9 （GLUT9）， urate transporter 1 （URAT1）， phospho-NF-κB p65 （p-NF-κB p65）， and nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 （NLRP3） in the renal tissue. ResultsCompared with the control group， the model group showed elevated levels of UA， Cr， BUN， ALT， and AST， increased activity of XOD in the liver（P<0.01）， raised levels of TNF-α， IL-1β and IL-18 in the serum（P<0.01）， and significantly up-regulated expression of GLUT9， URAT1， p-NF-κB p65， and NLRP3 in the renal tissue（P<0.01）. Compared with the model group， acacetin reduced the UA level in a dose-dependent manner， significantly improved liver and kidney functions， decreased the XOD activity in the liver， ameliorated the pathological changes in the renal tissue， down-regulated the expression of GLUT9， URAT1， p-NF-κB p65 and NLRP3 in the renal tissue（P<0.01）， and lowered the levels of TNF-α， IL-1β， and IL-18 in the serum（P<0.01）. ConclusionAcacetin can ameliorate HUA by decreasing uric acid production， increasing uric acid excretion， and inhibiting the NF-κB/NLRP3 signaling pathway. Therefore， acacetin may be a potential drug for the treatment of HUA.

Objective To explore the mechanism of Jiawei Jisheng Shenqi Decoction in improving the hypoxic microenvironment and antagonizing liver cirrhosis.Methods In vivo experiments were conducted using a rat model of carbon tetrachloride(CCL4)-induced liver cirrhosis.Rats were divided into normal,model,colchicine,JWJSSQ low-dose,JWJSSQ medium-dose,and JWJSSQ high-dose group.Pathological changes in liver tissues in each group were examined by hematoxylin and eosin(HE)and Masson staining,changes in serum liver function were detected using test kits,levels of hyaluronic acid(HA),laminin(LN),procollagen Ⅲ(PC Ⅲ),and collagen typeⅣ(COL4)were detected by enzyme-linked immunosorbent assay(ELISA),and protein expression levels of hypoxia-inducible factor-1α(HIF-1α),Notch1,Jagged1,and α-smooth muscle actin(α-SMA)were detected by Western blot.In vitro experiments were conducted in HSC-T6 cells,and the optimal concentration of CoCl2(100 μ mol/L,200μmol/L,400 μmol/L,600 μmol/L and 800 μmol/L)in the cultured cells and the optimal concentration of drug-containing serum(5％,10％,15％,20％)were determined by Cell Counting Kit-8(CCK-8)assay.The migration ability of cells in each group was detected by scratch testing,and changes in the apoptosis rates were determined by flow cytometry.Protein expression levels of HIF-1α,Notch1,Jagged1,α-SMA,matrix metallopeptidase 9(MMP9),and tissue inhibitor of metalloproteinases 1(TIMP-1)were detected by Western blot.Results In the in vivo experiments,liver swelling,inflammatory cell infiltration,collagen deposition,and the appearance of pseudolobules were significantly increased in the model group compared with those in the normal group.Serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),HA,LN,PCⅢ,and COL4 were significantly increased and albumin(ALB)was significantly decreased in the model group,while liver levels of HIF-1α,Notch1,Jagged1,and α-SMA proteins were significantly increased(P＜0.01).Liver swelling,inflammatory cell infiltration,and collagen deposition were significantly reduced in each treatment group compared with those in the model group,and the degree of fibrosis was reduced.Serum ALT,AST,HA,LN,PCⅢ,and COL4 were significantly decreased and ALB was significantly increased,while liver levels of HIF-1α,Notch1,Jagged1,and α-SMA proteins were also significantly decreased to varying degrees(P＜0.05).In the in vitro experiments,hypoxia promoted HSC-T6 migration and reduced apoptosis,increased the protein expression levels of HIF-1α,Notch1,Jagged1,α-SMA,and TIMP-1,and reduced the expression levels of MMP9(P＜0.01).Serum containing Jiawei Jisheng Shenqi Decoction inhibited HSC-T6 migration,promoted HSC-T6 apoptosis,lowered the expression of HIF-1α,Notch1,Jagged1,α-SMA,and TIMP-1 proteins,and enhanced the expression of MMP9 protein(P＜0.01).The inhibitory effect of Jiawei Jisheng Shenqi on HSC-T6 cell activation was reversed by the HIF-1α agonist dimethyloxalylglycine.Conclusions Jiawei Jisheng Shenqi Decoction can improve the hypoxic microenvironment via the HIF-1α/Notch pathway,thereby exerting an anti-liver cirrhosis effect.

Objective To explore time-related changes in renal function,renal injury biomarkers,and renal pathology in rats entering a low-pressure and low-oxygen(LPLO)environment simulating moving from the plains to a plateau.Methods Thirty male Sprague-Dawley rats were divided randomly into five groups(n=6 rats per group).Rats in the Control group were placed outside the chamber under normal pressure and oxygen conditions.Rats in the experimental groups were placed in an LPLO chamber to simulate a plateau environment at 5000 m above sea level,and were maintained in the chamber for 3,7,14,and 28 days,respectively.Serum levels of creatinine(CRE),cystatin C(CysC),neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),and interleukin-18(IL-18)were measured as biomarkers of renal injury.Pathological changes in the kidney were observed by hematoxylin and eosin and periodic acid-Schiff staining,with quantitative assessment of the following parameters:average glomerular diameter,peritubular capillary(PTC)density per tubule,tubular injury score,and outer medulla(OM)congestion score.Results NGAL,KIM-1,CysC,and CRE were significantly increased in the experimental compared with the Control group(all P＜0.05).The average glomerulus diameter was significantly reduced in the LPLO 3 d group and significantly increased in the LPLO 14 d group(both P＜0.05).The peritubular capillary(PTC)/tubule ratio was significantly decreased.The renal tubular injury and OM congestion scores were significantly increased(both P＜0.05).Regression analysis showed that PTC/tubule was linearly negatively correlated with the LPLO duration,while CRE,CysC,and pathological indicators(mean glomerular diameter,OM congestion score,renal tubular injury score)were curvilinearly correlated with the duration of LPLO(all P＜0.05).Variables with a curvilinear correlation were analyzed using restricted cubic splines(RCS).Each curve exhibited an inverted-L shape,with inflection points on day 7,indicating that the rate of increase of all indicators was highest within the first 7 days of LPLO,and the rate of increase then slowed from 7 days to 28 days.Conclusions A simulated move from a plains to a plateau environment was associated with significant structural and functional renal damage,but the kidneys then showed a self-adaptive adjustment process towards the plateau environment.

Objective To explore the application effect of the"Hospital-wide Centralized Bed Management"model in VIP wards,aiming to enhance medical service efficiency and patient experience through systematic resource integration and process optimization.Methods A VIP ward in a tertiary hospital in Southwest China was selected as the pilot site.From August 2024 to January 2025,a management model reform was implemented.Measures included the unified allocation of inpatient beds,construction of an information platform,establishment of interdisciplinary collaboration mechanisms,and optimization of medical staff responsibilities.Data on bed usage,service process indicators,and patient satisfaction were collected for three months before and after implementation.Statistical analysis was conducted using SPSS 26.0.Results After implementation,the bed utilization rate increased significantly from 20.0% to 55.0% (t=10.07,P＜0.001).The waiting time for admission was reduced from(48.0±12.5)hours to(23.5±6.8)hours(a 51.0% reduction,t=9.84,P＜0.001),and the bed transfer time decreased from(3.0±1.2)hours to(1.0±0.5)hours(a 66.7% reduction,t=7.62,P＜0.001).Patient satisfaction scores regarding bed arrangement,medical staff collaboration,and overall service significantly improved(all P＜0.001).After controlling for disease complexity,a strong positive correlation was found between bed utilization rate and overall satisfaction(r=0.68,P＜0.01).Conclusion By overcoming inter-departmental resource barriers,this model achieves efficient resource allocation and precise service process optimization in VIP wards,offering a replicable innovative approach for managing high-end medical serv-ices.

Objective:To explore the direct effect of safety organization on work engagement of Operating Room nurses, as well as the mediating effect of psychological capital between safety organization and work engagement, so as to provide theoretical basis for developing intervention programs to enhance work engagement of Operating Room nurses.Methods:From October to December 2024, convenience sampling was used to select 260 Operating Room nurses from three ClassⅢ Grade A hospitals as research subjects. Psychological Capital Questionnaire, Safety Organizing Scale, and Work Engagement Scale were used to survey Operating Room nurses. AMOS 26.0 software was used to analyze the mediating effect of Operating Room nurses' psychological capital between safety organization and work engagement.Results:A total of 260 questionnaires were distributed and 241 valid questionnaires were recovered, with a valid recovery rate of 92.69%. Among 241 Operating Room nurses, the total scores of Work Engagement Scale, Psychological Capital Questionnaire, and Safety Organizing Scale were (37.35±7.30), (90.10±11.62), and (41.58±10.82), respectively. The total score and scores of each dimension of the Work Engagement Scale were positively correlated with the total score and scores of each dimension of the Psychological Capital Questionnaire and the total score of the Safe Organizing Scale ( P<0.05). The total score and scores of each dimension of the Psychological Capital Questionnaire were positively correlated with the total score of the Safe Organizing Scale ( P<0.05). Mediating effect analysis showed that the direct effect of safety organization on work engagement of Operating Room nurses was established, with an effect value of 0.266 ( P<0.05). Psychological capital played a partially mediating effect between safety organization and work engagement of, with an effect value of 0.275, and the mediating effect accounted for 50.83% of the total effect. Conclusions:Safety organization has a positive impact on work engagement of Operating Room nurses, and psychological capital partially mediates the effect between safety organization and work engagement of Operating Room nurses. Hospital nursing administrators should be aware of the importance of building a safety organization and pay attention to building the psychological capital of Operating Room nurses so as to improve work engagement.

Objective:To develop a prehabilitation program for patients undergoing cervical spondylosis surgery, optimize preoperative management, and provide guidance for specialized clinical nursing.Methods:In March 2024, a prehabilitation team was established to extract the best available evidence on preoperative rehabilitation for cervical spondylosis through a literature review. After group discussions, an initial draft of the prehabilitation program was developed. Between April and May 2024, 20 experts were selected for a two-round Delphi consultation to finalize the program content. Expert engagement was measured by questionnaire response rates, while expert authority was evaluated using an authority coefficient. The degree of consensus among experts was assessed using Kendall's coefficient of concordance and the coefficient of variation.Results:The response rate for both rounds of expert consultation was 100.00% (20/20), with an authority coefficient of 0.93. In the first round, the coefficient of variation ranged from 0.06 to 0.20, and Kendall's coefficient of concordance was 0.121 ( P<0.01). In the second round, the coefficient of variation ranged from 0 to 0.16, and Kendall's coefficient of concordance was 0.108 ( P<0.01). The final prehabilitation program consisted of five primary categories (exercise intervention, nutrition support, psychological intervention, pain management, and thrombosis prevention), 15 secondary categories, and 31 tertiary categories. Conclusions:The prehabilitation program developed in this study demonstrates strong scientific validity and feasibility. It provides a theoretical framework and practical guidance for implementing preoperative prehabilitation for patients undergoing cervical spondylosis surgery.

Objective:To investigate the influencing factors on the acceptance of intermittent oro-esophageal tube feeding (IOE) in patients with dysphagia after stroke (DAS) .Methods:A convenience sampling method was used to select 260 DAS patients hospitalized in the Second Affiliated Hospital of Wenzhou Medical University from February 2022 to March 2024. The Visual Analog Scale (VAS) was applied to evaluate patients' acceptance of IOE. Additionally, the General Information Questionnaire, IOE Knowledge Questionnaire, Health Information Literacy Self-assessment Scale, Nurse-patient Relationship Trust Scale, and Family APGAR Index (APGAR) were used for investigation. Multiple linear regression was performed to analyze the influencing factors of IOE acceptance in DAS patients.Results:A total of 260 questionnaires were distributed, and 246 valid questionnaires were recovered, with a valid recovery rate of 94.62% (246/260). The results of multiple linear regression analysis showed that the Water Swallowing Test grade, IOE Knowledge Questionnaire score, Health Information Literacy Self-assessment Scale score, Nurse-patient Relationship Trust Scale score, and APGAR score were influencing factors for IOE acceptance in DAS patients ( P<0.05) . Conclusions:The influencing factors of IOE acceptance in DAS patients include the severity of dysphagia, IOE knowledge, health information literacy, nurse-patient relationship trust, and family care. Targeted interventions can be implemented based on these factors to promote the popularization of IOE.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.