Objective To establish a stable and reliable sepsis model of rat after liver transplantation (LT) for clinical translational research and analyze its characteristics. Methods The "two-sleeve method" was used to establish the in situ LT model of SD rats, and the sepsis model was constructed through cecal ligation and puncture (CLP) at 3 d after the operation. SD rats were randomly divided into 3 groups: sham operation group (Sham group), LT group, and LT + CLP group, with 6 rats in each group. The changes in body weight, rectal temperature and survival rate were compared, and the sepsis score was used for evaluation. The levels of blood biochemical indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (Urea), creatinine (Cr), creatine kinase (CK), lactate dehydrogenase (LDH)] and inflammatory factors [interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α] in each group were detected, and the pathological changes and cell apoptosis in different organs were observed. Results Compared with the Sham group, the body weight of the LT group and LT + CLP group decreased (all P<0.05). The rectal temperature of the LT + CLP group showed a continuous downward trend after the operation, the sepsis score increased sharply after the operation, and the survival rate dropped to 16.7%, and the differences between the Sham group, LT group and LT + CLP group were statistically significant (all P<0.05). The levels of ALT, AST, Urea, Cr, CK, LDH, and serum IL-1β, IL-6, IL-10 and TNF-α in the LT + CLP group were higher than those in the Sham group and LT group rats within 72 hours after the operation(all P<0.05). The pathological examination of the LT + CLP group showed severe tissue structure destruction, necrosis and infiltration of inflammatory cells in multiple organs, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining showed an increased level of cell apoptosis in multiple organs. Conclusions Using liver transplantation combined with CLP, a stable animal model of liver transplantation infection is successfully established, which exhibits a high mortality rate, significant multi-organ damage and intense inflammatory response, providing an ideal animal model for transplantation infection research.

The Proctor's reporting guideline for implementation strategies represents a landmark framework in the field of implementation science, aiming to address the issue of inconsistent reporting in implementation research by standardizing the naming, definition, and operationalization of implementation strategies, thereby enhancing the credibility and utility of research findings. This paper provides an in-depth interpretation of the core connotations of this reporting guideline and illustrates its application in developing interview outlines and specifying implementation strategies, using a brief smoking cessation intervention project as a case study. Through this reporting guideline, abstract recommendations for implementation are systematically transformed into clear, multidimensional operational guides, significantly improving the transparency of strategy connotations and the replicability of actual execution. Meanwhile, the case study highlights the flexibility of the guideline, which allows researchers to adapt the content and format of strategies based on local resources and cultural contexts, thus enhancing practical adaptability while maintaining scientific rigor. However, the application of Proctor's reporting guideline still faces challenges, primarily manifested in the potential confusion surrounding the constructs of temporality and dose in practice, as well as the challenges that the inherent flexibility of the guideline may pose to the assessment of fidelity and effectiveness. Despite these limitations, the reporting guideline remains a vital tool for implementation research; future efforts should focus on optimizing its application—through refining operational guidelines, standardizing flexible adaptations, and involving stakeholders—to better guide implementation studies and continuously promote high-quality development in the field.

Objective Titanium ions were implanted into Bio-HPP materials using plasma immersion ion implantation(PIII)technology,and the biocompatibility against human gingival fibroblasts(HGFs)and antimicrobial activity against porphyromonas gingivalis(P.g)to the materials were preliminarily evaluated.Methods The cell experiments and antibacterial experiments in vitro were conducted,and the specimens were randomly divided into the modified group and the control group,and the modified specimens were placed in an ion implantation device and implanted with titanium ions by PIII technology.The morphology of the nanostructures on the surface of the materials was observed by scanning electron microscopy.The cytocompatibility of Bio-HPP materials was evaluated by proliferation detection,immunofluorescence staining and cell cycle distribution detection of HGFs.The antibacterial activity of the materials was evaluated by the detection of antibacterial rate of P.g and the expression analysis of pathogenic gene,and the antibacterial mechanism was preliminarily analyzed.Results The surface of Bio-HPP in the control group was relatively flat,and the modified group formed nanopores with diameters of 100 to 300 nm,with smaller nanoparticles distributed in the nanostructures.The cell proliferation rates of HGFs after cultured for 3,5 and 7 days in the modified group were higher than those in the control group(P<0.05).After 4 hours of incubation,the cells spread well on the surface of the both groups,and the cytoskeleton extended further outward,while the spreading area on the surface of the control group was slightly smaller than that of the modified group.After 24 hours of incubation,the cells on the surface of materials in the both groups showed elongated spindle or shuttle shape,with good growth.There was no significant difference in the proportions of cells at stages G1 and G2 between the control group and the modified group(P>0.05).The proportion of cells at stage S in the modified group was higher than that in the control group(P<0.05).After 24 hours of incubation,the number of colonies in the modified group was significantly reduced compared with the control group;the antibacterial rate of the modified group was significantly higher than that of the control group(P<0.05).The relative expression of pathogenic genes fimA on the surface in the modified group was significantly lower than that in the control group(P<0.05).Conclusion Bio-HPP materials modified by titanium plasma implantation promotes the adhesion and proliferation of HGFs,which was conducive to the adhesion of soft tissues around the gingiva,with good antibacterial activity.

Objective:To investigate the effects of 10° head up tilt bed rest (HUT) on human cardiac function via 3D speckle tracking echocardiography (3D-STE), and to study the difference in cardiac function under the submaximal exercise load between the horizontal position and 10° HUBR.Methods:Thirty young healthy volunteers were recruited as the subjects, who were randomly divided into an 10° HUT exercise group and horizontal exercise group with 15 subjects in each. Subjects in both groups were asked to ride the bicycle ergometer in the 10° HUBR position and supine position respectively. The load started with 50 W and was increased by 25 W every 3 min until it reached the maximum of 125 W. Before the exercise (resting state), 1 min after the load was increased each time, and 3 min after exercise (recovery period), the following indices were collected: ①basic cardiac function indices: heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), ②conventional cardiac ultrasound indices: left ventricular ejection fraction (LVEF), stroke volume (SV) and cardiac output (CO), ③left ventricular strain indices: global longitudinal strain (GLS), global circumferential strain (GCS), and global area strain (GAS) measured by 3D-SET. The changes of these indices in the 2 groups of subjects under different exercise loads were observed.Results:The differences in the major effect of the basic heart indices (HR, SBP and DBP), conventional cardiac ultrasound indices (LVEF, SV and CO) and left ventricular strain indices (GLS, GCS and GAS) in response to the exercise load were statistically significant ( F=194.90, 113.66, 17.19, P=0.017, 0.018, 0.001). With the increase of the exercise load, the basic heart indices and conventional cardiac ultrasound indices kept rising, the left ventricular strain indices reached the minimum under a moderate exercise load (75 W), HR, SBP and CO were higher than those of the resting state ( P<0.05 or 0.01). Both LVEF under exercise loads of 75, 100, 125 W and during recovery, and SV under exercise loads of 100, 125 W and during recovery were significantly higher than those of the resting state ( P<0.05 or 0.01), while GLS and GCS under exercise loads of 50, 75, 125 W ( P<0.05 or 0.01), and GAS under exercise loads of 50, 75 W ( P<0.01) were significantly lower. There were statistically significant differences not only in GCS across the groups ( F=4.60, P=0.026) but also in DBP due to the interactions between the grouping and exercise loads ( F=3.13, P=0.031). DBP was higher than that of the resting state when the exercise load was 125 W in both groups. Conclusions:During submaximal exercise, myocardial contractility shows sustained enhancement with the increase of the exercise load. The results of GLS, GCS and GAS indicate that myocardial strain reaches its lowest value under a moderate exercise load, suggesting that moderate exercise can be used to evaluate cardiac function via 3D-SET. Under a simulated lunar gravity of 10° HUT, there is less deformation in the short axis direction of the myocardium, indicating that GCS can be used as a sensitive indicator to detect changes in cardiac function under different gravities.

Objective:To describe the distribution characteristics of alcohol consumption in adult twins in the Chinese National Twin Registry (CNTR), and further explore the influence of genetic factors on alcohol consumption in adult twins.Methods:The subjects of the study were twins registered by CNTR in 11 project areas across China from 2010 to 2018. A total of 56 966 twins (28 483 pairs) aged 18 years and above who answered questions about drinking behavior were included, and the random effect model was used to describe the population and regional distribution characteristics of alcohol consumption. Intra-pair analysis was performed to calculate the concordance rate and heritability of their alcohol consumption.Results:The age of all subjects was (36.6±12.0) years, and current drinkers accounted for 16.6% (9 461/56 966) of all subjects. In men, those aged 50-59 years, those in northern China, those living in rural area, those with low education level and those with high BMI, the proportions of current drinkers were higher. After excluding 468 pairs of twins who had stopped alcohol use and 21 764 pairs of twins who had no drink or had small amount drink, an intra-pair analysis was conducted in 4 929 pairs of same-sex twins, and found that the concordance rate of alcohol consumption was 64.0% (2 059/3 215) in monozygotic twins, and 52.6% (902/1 714) in dizygotic twins, the difference was significant ( P<0.001), and the heritability of alcohol consumption was 24.1% (95% CI: 18.9%- 29.3%). The further stratified analysis found that in southern men, the heritability was highest in those aged 40-49 years (36.1%, 95% CI: 21.6%-50.7%), while in northern men, the heritability was highest in those aged 50-59 years (34.2%, 95% CI: 18.1%-50.3%). Conclusions:In adult twins in China, there were population and regional differences in the distribution of alcohol consumption behavior, and alcohol consumption was influenced by genetic factors, and gender, age and region had potential modifying effects.

This study was aimed at understanding the relationships among the drug resistance and genome characteristics of group A Streptococcus in Jiangsu Province.A total of 149 group A Streptococcus strains were collected from hospitals between 2016 and 2023.Thirteen antimicrobial minimal inhibitory concentrations were detected with the micro-dilution broth method.The GAS strains were typed with emm genotyping analysis and whole genome sequencing,to determine the carriage rates of drug resistance genes and the evolutionary relationships among strains.The resistance rates of 149 GAS strains to erythromy-cin,tetracycline,and clindamycin exceeded 90％,whereas the strains showed sensitivity to 8 different antibiotics,including penicillin.Notably,the resistance rates to erythromycin,tetracycline,and clindamycin consistently increased over time.All strains were classified into 9 emm types,among which emm12 accounted for the highest proportion(77/149;51.68％).Signifi-cant statistical differences were observed among emm types,in terms of the drug resistance rate,number of resistant species,and prevalence of drug resistance genes.Furthermore,SNP evolutionary tree analysis revealed 3 distinct clusters within the GAS strains:emm12,emm1,and other emm types.emm 12 and emm1 were the dominant GAS strains in Jiangsu Province.Most isolates were resistant to erythromycin,tetracycline,and clindamycin.Differences in phenotypes and genomic characteris-tics were observed among emm types.

Objective:To investigate the feasibility and optimal expansion width of replacing the left anterior descending coronary artery (LADCA) with the region of heart sparing (RHS) to reduce cardiac radiation dose during breast cancer radiotherapy.Methods:Retrospective analysis was conducted on data from 88 patients with left-sided breast cancer who underwent radiotherapy at 2 centers: Nanfang Hospital of Southern Medical University (50 cases for the training set, 15 cases for the internal test set) and Ganzhou Hospital of Nanfang Hospital (23 cases for the external test set) from March 2022 to January 2024. All patients had left-sided invasive ductal carcinoma with axillary lymph node metastasis, and had undergone modified radical mastectomy and chemotherapy. Based on simulation CT images, 2 radiation oncologists delineated the LADCA and 8 RHSs. The RHSs were delineated by expanding the LADCA contour by 0.5 cm increments, totaling 8 expansions. The RHS widths were defined as 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4.0 cm. The nnU-Net model was trained for 3D automatic segmentation of the LADCA and RHSs. Model performance was evaluated using the Dice similarity coefficient (DSC), relative volume error (RVE), sensitivity, specificity, and 95% Hausdorff distance (HD95). Additionally, the minimum, maximum, and average relative dose variations (RDV) as well as V5% and V20% indicators were calculated for the LADCA and each RHS. Correlation analysis was performed using the least squares regression, with the slope and coefficient of determination ( R2) employed to evaluate the accuracy of the model fitting, the relationship between the LADCA and RHS, and the degree of their correlation, thereby assessing the substitutive effect of the RHS for the LADCA. Results:The DSC for the LADCA was 0.415, while the DSCs for RHS widths of 0.5 cm and 4.0 cm were 0.718 and 0.835, respectively. Overall, the automatic segmentation performance improved with increasing RHS width. The DSC, RVE, sensitivity, specificity, and HD95 for the external test set were largely consistent with those of the internal test set, demonstrating the model's good robustness across different datasets. All RDVmin values were negative, while RDVmax and RDVmean showed a positive correlation with RHS width. RDVmean increased from 39.01% to 75.89% as the RHS width increased. In the correlation analysis, the slopes for RHS widths of 1.5 cm and 2.0 cm were 0.95 and 1.05, respectively, with R2 values and coefficients of variation of 0.79 and 0.73, and 21.11% and 24.03%, respectively. Conclusions:The automatic segmentation model trained on nnU-Net can accurately segment RHSs. Based on geometric and dosimetric indicators, a 1.5 cm-wide RHS is the most suitable substitute for the LADCA, effectively limiting the radiation dose to the LADCA without compromising target dose coverage.

Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.

Background and aims:Environmental pollutants,particularly organochlorine insecticides like endosulfan(ENDO),are increasingly linked to liver toxicity and related diseases.Despite its widespread historical use,the mechanisms underlying ENDO-induced liver damage remain poorly understood.This study aims to elucidate the cellular and molecular mechanisms of ENDO-induced hepatotoxicity.Methods:C57BL/6 mice were exposed to ENDO for two weeks.Single-cell RNA sequencing(scRNA-seq)was subsequently performed on mouse livers to explore ENDO-induced hepatotoxicity at the single-cell level.Differentially expressed genes(DEGs)across cell types and treatments were identified and then subjected to pathway enrichment to uncover key biological processes affected by ENDO.Transcription factor(TF)regulatory network,pseudotime trajectory,and cellular communication analysis were used to explore the molecular and cellular changes after ENDO exposure.Results:ENDO not only caused direct hepatocyte injury but also activated hepatic stellate cells and lymphocytes,triggering inflammatory responses with upregulation of multiple key chemokines and cytotoxic genes.Additionally,ENDO exposure led to the recruitment and activation of myeloid cells,contributing to the inflammatory milieu.An increase in intercellular communication and changes to the hepatic microenvironment,especially the interaction between activated hepatic stellate cells and CD8+T cells were observed,further implicating these processes in ENDO-induced liver damage.Conclusions:This study provides new insights into the cellular and molecular mechanisms underlying liver injury induced by organochlorine insecticides like ENDO.Key genes and pathways involved in ENDO-associated liver toxicity have been identified at a single-cell resolution.These findings suggest that altered cellular communications and inflammatory responses may play pivotal roles in the pathogenesis of ENDO-induced liver injury.

Pheochromocytoma is a neuroendocrine tumor that produces catecholamines, leading to elevated blood pressure and metabolic changes in patients. It can result in serious complications affecting the heart, brain, kidneys, and blood vessels, potentially becoming a primary cause of death. Most pheochromocytoma patients present with atypical symptoms, making misdiagnosis or missed diagnosis common. This article reports a case of pheochromocytoma crisis misdiagnosed as severe viral myocarditis and includes a review of the relevant literature.