Objective To investigate the impact of anticentromere antibody(ACA)on the clinical features and prognosis of patients with primary biliary cholangitis(PBC)by comparing clinical classification,ursodeoxycholic acid(UDCA)response,GLOBE score,and UK-PBC score between ACA-positive PBC patients and ACA-negative PBC patients.Methods A total of 749 patients who were admitted to Beijing Ditan Hospital,Capital Medical University,from August 2013 to December 2022 and were diagnosed with PBC were enrolled and divided into ACA-positive group with 147 patients and ACA-negative group with 602 patients.According to their conditions on admission,the two groups were compared in terms of the distribution of clinical types,i.e.,chronic progression-type PBC,portal hypertension-type PBC,and standard jaundice/liver failure-type PBC.There were 261 patients with complete data after 1-year follow-up,among whom there were 53 patients with positive ACA and 208 with negative ACA.A statistical analysis was performed,and propensity score matching was performed based on sex and age at a ratio of 1∶2.The two groups were compared in terms of 1-year UDCA response rate,GLOBE score,and UK-PBC score before and after matching.The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.Results Compared with the ACA-negative group,the ACA-positive group had a significantly higher age(61.28±10.35 years vs 56.74±12.17 years,t=4.164,P<0.001),a significantly higher proportion of female patients(93.9%vs 77.6%,χ2=20.221,P<0.001),a significantly higher proportion of patients with portal hypertension(48.3%vs 27.6%,χ2=23.289,P<0.001),and a significantly lower proportion of patients with jaundice/liver failure(24.5%vs 38.5%,χ2=10.205,P<0.001).After 1-year follow-up,for the 261 PBC patients with complete data,there was no significant difference in UDCA response rate before propensity score matching between the ACA-positive group and the ACA-negative group(41.5%vs 41.8%,P>0.05),and there was a significant difference in the proportion of patients with a GLOBE score of>0.3 between the ACA-positive group and the ACA-negative group(92.5%vs 80.3%,χ2=3.935,P=0.047).There were 53 patients in the ACA-positive group and 106 patients in the ACA-negative group after propensity score matching,and there were no significant differences between the two groups in UDCA response rate,GLOBE score,and UK-PBC score(all P>0.05).Conclusion ACA-positive patients tend to have an older age,with a higher proportion of female patients or patients with portal hypertension,while there is a relatively low proportion of patients with jaundice/liver failure.Positive ACA has no significant impact on UDCA response rate,GLOBE score,and UK-PBC score.

BACKGROUND:Extracellular vesicles have received extensive attention in the field of bone defect regeneration and repair in recent years.However,natural extracellular vesicles have deficiencies in sustained controlled release,tissue targeting,and drug loading capacity.Therefore,the introduction of engineering strategies to modify extracellular vesicles to enhance their therapeutic efficacy has become a research hotspot.OBJECTIVE:To review the role and application progress of engineered extracellular vesicles in the regeneration and repair of bone defects.METHODS:PubMed,Web of Science,CNKI,and WanFang databases were searched for relevant articles published in the past fifteen years.The search terms were"engineering,extracellular vesicles,exosomes,bone defect,bone regeneration,bone repair"in Chinese and English.After removal of poorly related,outdated,and duplicate studies by screening,93 articles were finally included for review according to inclusion criteria.RESULTS AND CONCLUSION:(1)Extracellular vesicles are primarily isolated based on their density,size,immunoaffinity,and surface charge.After isolation,extracellular vesicles are characterized using imaging techniques,size-and counting-based techniques,and flow cytometry.(2)Extracellular vesicles stimulate bone regeneration by regulating immunity,angiogenesis,and proliferation and differentiation of target cells.(3)The engineering strategies of extracellular vesicles include surface modification and cargo loading.(4)The introduction of bone morphogenetic protein 2,mutant hypoxia-inducible factor-1α,vascular endothelial growth factor,miRNA and other bioactive factors into extracellular vesicles through engineering strategies can enhance their regenerative repair ability for bone defects.

Objective To develop the Children's Screen Interaction Quality Questionnaire(CSIQ)suit-able for measuring Chinese children aged 0 to 4 years,and to test its reliability and validity.Methods The purposive sampling method was used,and the guardians of 30 normal children aged 0 to 4 years undergoing physical examinations in the Department of Child Health Care of Guiyang Maternal and Child Health Care Hospital from February to April 2023 were selected as the interview objects.25 initial items were constructed through literature review,semi-structured interviews,and the Delphi expert consultation method.With the convenience sampling method,2 242 guardians of children aged 0 to 4 years old in the small and middle classes of 9 kindergartens in Guiyang City,Zunyi City,and Renhuai City were surveyed for item analysis,exploratory factor analysis,confirmatory factor analysis,and reliability and validity analysis.Results Exploratory factor a-nalysis extracted three factors,namely screen content interaction,reality interaction,and media interaction,with a total of 12 items.The cumulative variance explained rate of the 3-factor model was 69.829％.Confirma-tory factor analysis supported the three-factor model of CSIQ:x2/df=4.424,root mean square error of ap-proximation(RMSEA)=0.066,normed fit index(NFI)=0.955,comparative fit index(CFI)=0.965,incre-mental fit index(IFI)=0.965,Tucker-Lewis index(TLI)=0.955,goodness-of-fit index(GFI)=0.955,and the CSIQ had good convergent validity and discriminant validity.Conclusion The CSIQ has good reliability and validity.

Objective To systematically integrate the best evidence on pulmonary rehabilitation nursing for patients with tracheostomy after stroke(TAS),so as to provide evidence-based basis for clinical practice.Methods Following evidence-based medicine principles,we conducted a systematic search of literatures related to pulmonary rehabilitation nursing for patients with TAS in databases including UpToDate,BMJ Best Practice,PubMed,China National Knowledge Infrastructure(CNKI),Wanfang Database,VIP Database,and China Biology Medicine(CBM).Literature types included guidelines,expert consensus,systematic reviews,meta-analyses,evidence summaries,and original studies,with the search period spanning from the inception of the database to Jan.2025.Two researchers independently assessed the quality of the included literatures using standardized tools such as Appraisal of Guidelines for Research and Evaluation-Ⅱ and Joanna Briggs Institute tools,followed by grading and synthesizing evidences meeting the criteria.Results A total of 20 articles were included,including 6 guidelines,5 expert consensuses,4 meta-analyses,3 clinical decision-making papers,1 systematic review,and 1 randomized controlled trial.A total of 32 recommendations were formed,covering 6 dimensions:airway management(8 items),comprehensive pulmonary rehabilitation training(8 items),basic treatment(5 items),safety management(4 items),extubation nursing(3 items)and prevention of complications during the peri-extubation period(4 items).The evidence grades ranged from grade A(strong recommendation)to grade B(recommendation).Conclusion This study systematically synthesizes core elements of pulmonary rehabilitation nursing for patients with TAS through evidence-based methodology.The established multidimensional evidence framework provides scientific guidance for improving respiratory function,reducing complications,and optimizing extubation decisions.Clinicians are advised to adapt these recommendations to local contexts for practical implementation.

Objective To develop a nurse-led dynamic monitoring protocol for fluid responsiveness and to evaluate its effectiveness in preventing fluid accumulation syndrome in patients with septic shock.Methods A nurse-led dynamic monitoring protocol for fluid responsiveness was developed through literature review and expert panel discussion.Using convenience sampling,160 patients with septic shock admitted to the emergency department of a tertiary hospital in Hangzhou,Zhejiang Province,were enrolled.According to admission period,80 patients admitted from November 2023 to August 2024 were assigned to an intervention group,and 80 patients admitted from January 2023 to October 2023 were assigned to a control group.The intervention group received the nurse-led dynamic monitoring in addition to routine care,while the control group received routine care and conventional fluid responsiveness monitoring.The therapeutic outcomes and incidence of complications were compared between the 2 groups.Results All 80 patients in each group completed the study.The intervention group demonstrated higher lactate clearance rates at 6 and 24 hours after fluid resuscitation,lower incidences of acute pulmonary edema and fluid accumulation syndrome,and shortened durations of mechanical ventilation and ICU stay(all P＜0.05)compared to the control group.There was no statistically significant difference in 28-day mortality between the 2 groups(P=0.212).Conclusion The nurse-led dynamic monitoring protocol for fluid responsiveness in patients with septic shock is both scientific and practical.Its implementation can effectively improve lactate clearance,reduce the incidence of fluid accumulation syndrome and acute pulmonary edema,and shorten the duration of mechanical ventilation and ICU stay.

Objective:To reveal the global evolution, cooperation models and research hotspots of wounds with drug-resistant bacterial infections in the elderly, and provide information support for future research directions.Methods:All literatures on wounds with drug-resistant bacterial infections in the elderly were retrieved from the Web of Science Core Collection. Bibliometric analysis was performed using CiteSpace and VOSviewer to visualize contributions from countries/regions, institutions, authors and journals, and to analyze keyword co-occurrence and temporal evolution.Results:After strict screening, a total of 130 literatures were included. Global research achievements on wounds with drug-resistant bacterial infections in the elderly showed a continuous growth. The United States was the main contributor in terms of the number of literatures, followed by Spain, Germany and the United Kingdom. However, international cooperation was still limited, and the institutional network was sparse. The most significant burst keywords at present included " risk factors", " methicillin-resistant", " inpatients", " molecular epidemiology", " Staphylococcus aureus", " long-term care facilities", " nosocomial infections", " mortality", " pressure ulcers", " complex wounds" and " emerging drug-resistant bacteria" .Conclusions:In the future, priority must be given to in-depth research on the pathogenesis of wounds with drug-resistant bacterial infections in the elderly (epidemiological investigation of drug-resistant bacterial infections in elderly patients, interaction between single cells of aging wounds and drug-resistant microbiome); verification of the mode and effect of stratified precise treatment through multi-country trials; and establishment of a professional database through data collection and multi-modal information integration.

Objective:To explore the aperiodic components(1/f slopes)and their associations with cognitive impairment in patients with schizophrenia.Methods:Nineteen patients with schizophrenia according to the Interna-tional Statistical Classification of Diseases and Related Health Problem,Tenth Revision(ICD-10)and 21 normal controls were administrated the total Brief Assessment of Cognition in Schizophrenia(BACS)to measure the cogni-tive performance.The 5-minute eyes-closed and eyes-open resting EEG signals were collected and parameterized in-to aperiodic components(1/f slope).Finally,Pearson correlation was used to examine the relationships between the 1/f slope and cognition assessment scores.Results:The patients with schizophrenia had higher 1/f slope compared to HC on central location of scalp(P＜0.05).The vocal memory scores showed a significantly positive relation with 1/f slopes in patients with schizophrenia(anterior location:r=-0.68,P＜0.05;central location:r=-0.44,P＜0.05),but a significantly negative relation in normal controls(anterior location:r=0.57,P＜0.05;posterior lo-cation:r=0.54,P＜0.05).Conclusion:The 1/f slopes of EEG in schizophrenia were steeper than normal control,suggesting its strong cognitive functional significance and complex mechanisms in schizophrenia.

OBJECTIVES: The prevalence of overweight and obesity among children and adolescents continues to rise, becoming one of the most serious global public health issues of the 21st century. Given the differing growth and development environments between urban and rural children, associated risk factors also vary. This study aims to explore the distribution characteristics and influencing factors of overweight and obesity among urban and rural primary and secondary school students in Hunan Province, providing scientific evidence for targeted interventions. METHODS: A stratified, randomized cluster sampling method was used to select participants. A total of 197 084 students from primary and secondary schools across 14 prefectures in Hunan Province underwent physical examinations and questionnaire surveys. Population and spatial distribution characteristics of overweight and obesity were analyzed. Spatial distribution maps and spatial autocorrelation analyses were conducted using ArcGIS. Multivariate Logistic regression was used to identify influencing factors for overweight and obesity. RESULTS: The overall overweight and obesity rates among students in Hunan Province were 14.7% and 10.9%, respectively. Both rates were higher in urban areas than in rural counties (16.0% vs 13.9% for overweight; 12.1% vs 10.2% for obesity). Among both urban and rural students, boys had higher rates of overweight and obesity than girls. Higher-grade students had a higher overweight rate but a lower obesity rate than lower-grade students. In urban areas, the overweight and obesity rates of Han Chinese primary and secondary school students are lower than those of ethnic minority students (both P<0.05). In rural areas, the obesity rate of Han primary and secondary school students is lower than that of ethnic students (P<0.05). Across cities and prefectures, urban overweight and obesity rates ranged from 14.7% to 18.7% and 8.4% to 20.6% respectively, while rural rates ranged from 10.9% to 17.2% and 6.6% to 13.7% respectively. Spatial autocorrelation analysis revealed high-value clusters of overweight/obesity in urban areas of Changde and Zhangjiajie, and in rural areas of Loudi, Huaihua, and Shaoyang. Multivariate Logistic regression showed that gender, school stage, ethnicity, frequency of fresh vegetable intake, and sleep duration were associated with overweight and/or obesity in both urban and rural students. In urban students, frequency of fried food and fresh fruit intake, breakfast habits, physical activity on weekdays and holidays, and screen time on computers were also significant. In rural students, TV viewing time and sedentary duration were additional relevant factors. CONCLUSIONS The situation of overweight and obesity among primary and secondary school students in Hunan Province remains concerning. Greater attention should be paid to regions with high-value clusters of overweight/obesity, and targeted interventions should be developed based on urban-rural differences in influencing factors.
Humans ; China/epidemiology* ; Adolescent ; Male ; Female ; Rural Population/statistics & numerical data* ; Child ; Overweight/epidemiology* ; Students/statistics & numerical data* ; Urban Population/statistics & numerical data* ; Risk Factors ; Prevalence ; Obesity/epidemiology* ; Surveys and Questionnaires ; Pediatric Obesity/epidemiology* ; Schools

OBJECTIVES: Keloids are fibrotic skin disorders characterized by excessive collagen deposition and a high recurrence rate, closely associated with inflammatory mediators. However, existing epidemiological studies are limited by confounding factors and reverse causality, making it difficult to establish causation. This study aims to investigate the causal relationship between circulating cytokines and keloids using Mendelian randomization analysis. METHODS: Significant single nucleotide polymorphisms (SNPs) associated with circulating cytokines (exposures) and keloids (outcomes) were extracted from genome-wide association study (GWAS) summary datasets. Eligible SNPs were selected as instrumental variables (IVs). Exposure data were derived from a cytokine GWAS including 8 293 Finnish participants, and outcome data from a keloid GWAS based on the UK Biobank. The inverse-variance weighted (IVW) method served as the primary analytical approach to estimate causal effects, supplemented by weighted median (WME), MR-Egger regression, and other sensitivity analyses. Horizontal pleiotropy was assessed using MR-Egger regression and the MR pleiotropy residual sum and outlier (MR-PRESSO) test, while Cochran's Q test evaluated heterogeneity. Leave-one-out analysis was used to verify robustness and consistency. A reverse MR analysis was also conducted, with keloid as the exposure and cytokines as outcomes, to rule out reverse causation. RESULTS: IVW analysis identified significant positive causal associations between two cytokines and keloids-macrophage migration inhibitory factor (MIF) [odds ratio (OR)=2.081, 95% confidence interval (CI) 1.219 to 3.552, P=0.007] and monocyte chemoattractant protein-1 (MCP-1) (OR=1.673, 95% CI 1.036 to 2.701, P=0.035). Conversely, stem cell factor (SCF) showed a negative causal relationship with keloids (OR=0.518, 95% CI 0.269 to 0.998, P=0.049). Results from the MR-Egger and weighted median analyses were consistent with IVW findings. No evidence of horizontal pleiotropy was observed (P>0.05). Except for interleukin-6 (P=0.014), no heterogeneity was detected in other cytokines. Leave-one-out analysis further confirmed the robustness of the causal associations. In reverse MR analysis, keloids were causally related only to β-nerve growth factor (beta-NGF) (OR=1.048, 95% CI 1.002 to 1.095, P=0.039), with no heterogeneity or pleiotropy detected in most cytokines (P>0.05). CONCLUSIONS MIF and MCP-1 exhibit positive causal associations with keloid formation, while SCF shows a negative causal relationship. These findings provide new evidence for the causal involvement of inflammatory cytokines in keloid pathogenesis and offer potential molecular targets for developing novel keloid therapies.
Humans ; Keloid/blood* ; Mendelian Randomization Analysis ; Cytokines/genetics* ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; Chemokine CCL2/genetics* ; Interleukin-6/genetics* ; Macrophage Migration-Inhibitory Factors/genetics* ; Male ; Stem Cell Factor/blood* ; Female ; Intramolecular Oxidoreductases

Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.