In current clinical practice, various dermal templates and skin substitutes are used to enhance wound healing. However, the role of wound commensal microbiome in regulating scaffold performance and the healing process remains unclear. In this study, we investigated the influence of both natural and synthetic scaffolds on the wound commensal microbiome and wound repair in three distinct models including diabetic wounds, burn injuries, and germ-free (GF) wounds. Remarkably, synthetic electrospun polycaprolactone (PCL) scaffolds were observed to positively promote microbiome diversity, leading to enhanced diabetic wound healing compared to the natural scaffolds Integra® (INT) and MatriDerm® (MAD). In contrast, both natural and synthetic scaffolds exhibited comparable effects on the diversity of the microbiome and the healing of burn injuries. In GF wounds with no detectable microorganisms, a reversed healing rate was noted showing natural scaffold (MAD) accelerated wound repair compared to the open or the synthetic scaffold (PCL) treatment. Furthermore, the response of the wound commensal microbiome to PCL scaffolds appears pivotal in promoting anti-inflammatory factors during diabetic wound healing. Our results emphasize that the wound commensal microbiome, mediated by different scaffolds plays an important role in the wound healing process.

OBJECTIVES: To explore the mechanism by which histone deacetylase 1 (HDAC1) regulates steroid-induced apoptosis of mouse osteocyte-like MLO-Y4 cells. METHODS: MLY-O4 cells were treated with 400 nmol/L trichostatin A (TSA) or 1 mmol/L dexamethasone for 24 h or transfected with a HDAC1-overexpressing vector prior to TSA or dexamethasone treatment. The changes in the expressions of HDAC1, SP1, cleaved caspase-3 and Bax, SP1 acetylation level, cell proliferation, and cell apoptosis were examined. The interaction between HDAC1 and SP1 was determined with immunoprecipitation assay and Western blotting. RESULTS: Treatment with dexamethasone significantly increased cell apoptosis, enhanced the expressions of cleaved caspase-3 and Bax, reduced HDAC1 expression, and suppressed proliferation of MLO-Y4 cells. Both TSA and dexamethasone obviously increased SP1 acetylation level and the expression of SP1 in MLO-Y4 cells. HDAC1 overexpression in the cells significantly attenuated the effect of TSA and dexamethasone, promoted cell proliferation, lowered the expressions of SP1, cleaved caspase-3 and Bax, and inhibited dexamethasone-induced cell apoptosis. Immunoprecipitation assay and Western blotting demonstrated the interaction between HDAC1 and SP1 in the cells. CONCLUSIONS HDAC1 inhibits dexamethasone-induced apoptosis and promotes proliferation of cultured mouse osteocytes by suppressing SP1 expression via promoting its deacetylation.
Animals ; Apoptosis/drug effects* ; Mice ; Histone Deacetylase 1/genetics* ; Osteocytes/drug effects* ; Sp1 Transcription Factor/metabolism* ; Acetylation ; Dexamethasone/pharmacology* ; Cell Proliferation/drug effects* ; Caspase 3/metabolism* ; Cell Line ; Hydroxamic Acids/pharmacology* ; bcl-2-Associated X Protein/metabolism*

Objective:To validate the effectiveness of the leaf position data of multi-leaf collimator (MLC) recorded in the Infinity medical linear accelerator log file (LF).Methods:In this study, the establishment of the film dose calibration curve involved two steps. Initially, the pixel values obtained from scanning the film were converted into net optical density values. Subsequently, a sixth-order polynomial fit was performed on the net optical density and dose data. The picket fence (PF) tests were performed on the electronic portal imaging device (EPID) and film, and the corresponding acquired PF test images were analyzed using the relative leaf travel distance, relative leaf position, relative leaf pair full-width half -maximum (FWHM), and relative leaf pair neighbor region width analysis index, and compared with the relevant results in LF. In addition, to investigate the effect of gravity on the recorded leaf position data by the Infinity medical linear accelerator LF, the above PF tests were executed at 0°, 90°, 180°, and 270° gantry angles, respectively. Intergroup differences were assessed with the Wilcoxon rank-sum test.Results:The film dose calibration curve demonstrated high goodness-of-fit, with a correlation coefficient ( R2) of 0.9994. Across all gantry angles, the dispersion of overall leaf position data for EBT3 film, EPID, and LF followed a consistent pattern based on four analysis metrics: EBT3 film > EPID > LF. Moreover, for each analysis metric, inter-tool differences in standard deviations of results were consistently below 0.1 mm, and this pattern was invariant to gantry angle. Conclusions:The leaf position data recorded in the Infinity medical linear accelerator LF have a high degree of accuracy, and can be used as reference for the actual position of the MLC leaf. Furthermore, gravitational forces exhibit negligible impact on leaf position data acquired via LF.

Purpose To evaluate the diagnostic accuracy of low-iodine contrast subtraction CT pulmonary angiography(CTPA)combined with iodine maps for acute pulmonary embolism(APE),with a focus on detecting subsegmental emboli.Materials and Methods A retrospective analysis included 48 patients with suspected APE who underwent both pulmonary ventilation/perfusion SPECT/CT and low-iodine subtraction CTPA within one week in Beijing Hospital from September 1,2021 to September 1,2024.Using SPECT/CT as the reference standard,the diagnostic performance of subtraction CTPA with iodine maps was assessed.A retrospective review was performed to identify potential causes of false-positive and false-negative results.Results Subtraction CTPA with iodine maps demonstrated high diagnostic accuracy at the segmental and subsegmental pulmonary artery levels,with a sensitivity of 0.917 and specificity of 0.991.At the segmental level,the detection rate was 100%,while at the subsegmental level,it was 66.7%.The method showed consistently high diagnostic performance(83.3%-100%)across different clinical risk stratifications of APE.Retrospective review identified explicable causes for 85.7%(6/7)of false-positive and 33.3%(2/6)of false-negative cases.Conclusion Low-iodine subtraction CTPA combined with iodine maps exhibits robust diagnostic efficacy for APE.Accurate recognition of characteristic perfusion defects on iodine maps may further enhance diagnostic precision.

Mitophagy,a critical regulator of knee joint homeostasis,its dysfunction can lead to pathological changes such as reactive oxygen species overproduction,calcium ion overload,and extracellular matrix degradation,inducing cartilage degeneration and serving as a key pathological mechanism of knee osteoarthritis(KOA)."Deficient qi stagnation"represents the core pathogenesis of KOA.Mitochondria,analogous in function to qi and serving as its microscopic manifestation,exhibit a high degree of congruence between mitophagy and the defensive functions of qi.Based on the pathogenic characteristics of"deficient qi stagnation"of KOA,and integrating modern medical explanations of mitophagy,this article believed that the deficiency of liver,spleen and kidney qi is the fundamental reason for the imbalance of mitochondrial autophagy in KOA,and the retention of pathogenic toxins is the key factor in the imbalance of mitochondrial autophagy.The basic treatment method of tonifying qi and strengthening the body,promoting blood circulation and promoting stagnation can provide clinical formula ideas for the TCM prevention and treatment of KOA.

Breast cancer is the most common malignant tumor in women worldwide,and its incidence rate is increasing annually.Early dia-gnosis is essential for improving patient prognosis.In recent years,artificial intelligence(AI)technology has emerged as a transformative tool,providing new directions for accurate diagnostic and prognostic assessments.This article systematically reviews research progress in the ap-plication of AI to breast cancer screening,multimodal imaging techniques for diagnosis,pathological diagnosis,treatment,and prognostic modeling.Through machine learning and deep learning algorithms,AI has demonstrated significant advantages in the enhancement of dia-gnostic accuracy,efficiency,and accessibility,including improvement of the detection rate of small lesions,reduction in the radiologists'workload,and optimization of treatment decisions.Despite challenges,including the integration of explainable technology in clinical trans-formation,lack of data standardization,complexity of multimodal data,and risk of model generalization,AI is expected to play a more prom-inent role in the precise diagnosis and intelligent therapy for breast cancer,thereby contributing to the full realization of the goal of preci-sion medicine.

Objective:To investigate the effects of low tube voltage, automatic tube current modulation technology combined with noise index(NI), and forward projected model-based iterative reconstruction solution(FIRST)on radiation dose and image quality in low iodine contrast agent CT pulmonary angiography(CTPA)among elderly patients.Methods:This retrospective study continuously collected imaging and clinical data from elderly patients suspected of having acute pulmonary embolism (APE)who underwent low-iodine contrast CTPA at the emergency department and inpatient department of Beijing Hospital from February 2022 to July 2023.A total of 80 patients were included in the study.Based on the reconstruction algorithm utilized during the CTPA examination, the patients were divided into two groups: the adaptive iterative dose reduction using three-dimensional processing(AIDR 3D)group and the FIRST group, with 40 cases in each group.We measured the average CT value and noise value of the pulmonary artery at various positions in both groups on axial images, calculated the signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR), and recorded the average tube current and effective radiation dose for both patient groups.Two observers independently performed subjective scoring on the display of the pulmonary artery in each group using a blind method.Results:There were no statistically significant differences in age, body mass index (BMI), gender, and the extent of pulmonary embolism between the AIDR 3D group and the FIRST group (all P>0.05).In comparison to the AIDR 3D group, the FIRST group exhibited a significantly lower tube current[(220.2±84.5) mA vs.(264.1±81.2) mA, t=0.463, P=0.020], resulting in an effective radiation dose reduction of 15.7%[(1.39±0.49) mSv vs.(1.65±0.41) mSv, t=0.072, P=0.043].No statistically significant differences were observed in the mean CT values, noise values, and SNR values of the main pulmonary artery, left and right pulmonary trunks, and lobar and segmental pulmonary arteries between the AIDR 3D group and the FIRST group (all P>0.05).The CNR of the AIDR 3D group was lower than that of the FIRST group in both the left and right segmental pulmonary arteries( Z=-2.473, -1.973; P=0.013, 0.049), while no significant differences were found in the other pulmonary arteries(all P>0.05).In patients with normal BMI, the FIRST group demonstrated higher CNR values in both the left and right segmental pulmonary arteries compared to the AIDR 3D group( Z=-2.008, -2.662, P=0.046, 0.007), whereas the improvement in CNR was not significant in overweight and obese patients(all P>0.05).The two radiologists provided consistent subjective evaluations in scoring(Kappa=0.744, P<0.001), and there was no statistically significant difference in subjective scores between the AIDR 3D group and the FIRST group ( χ2=0.346, P=0.770). Conclusions:The imaging technique that integrates automatic tube current modulation technology with NI, the FIRST reconstruction algorithm, and a low tube voltage of 100 kVp effectively ensures image quality by providing clear visualization of pulmonary arteries at all levels.Moreover, it reduces radiation dose during low-iodine contrast agent CTPA examinations in elderly patients with APE.

Objective:To evaluate the prevalence, potential risk factors, and correlation between coronary and peripheral microvascular dysfunction in heart failure with non-reduced ejection fraction (nHFrEF) patients.Methods:This was a prospective registry study. nHFrEF patients admitted to Zhongshan Hospital affiliated with Fudan University from December 2021 to December 2023 were enrolled. According to coronary flow reserve (CFR) or reactive congestion index (RHI), enrolled patients were divided into coronary microvascular endothelial dysfunction (CMD) group (CFR<2.5) and no CMD group (CFR≥2.5) or peripheral microvascular endothelial dysfunction (MED) group (RHI<1.67) and no MED group (RHI≥1.67). Patients′ general information, laboratory and auxiliary examination data were collected. Univariate and multivariate logistic regression were used to analyze the influencing factors of CMD and MED in nHFrEF patients, and Spearman correlation analysis was used to evaluate the correlation between MED and CMD.Results:A total of 142 nHFrEF patients were enrolled, aged 69.0 (59.0, 74.0) years, with a male proportion of 66.9% (95/142). The grouping results were as follows: (1) According to CFR, there were 73 cases in the CMD group and 69 cases in the no CMD group; (2) According to RHI, there were 57 cases in the MED group and 85 cases in the no MED group. The prevalence of CMD and MED in this study was 51.4% (73/142) and 40.1% (57/142), respectively. Univariate logistic regression analysis showed that increased heart rate, chronic kidney disease, atrial fibrillation, elevated N-terminal pro-B type natriuretic peptide levels, and increased urinary albumin/creatinine ratio were risk factors for CMD, while increased RHI was a protective factor for CMD; Atrial fibrillation is a risk factor for MED, while increased CFR is a protective factor for MED. Incorporating clinically significant variables from univariate analysis into multivariate analysis, the results showed that increased heart rate and elevated RHI remained risk and protective factors for CMD, respectively; increased CFR remains a protective factor for MED. Spearman correlation analysis showed that CFR was negatively correlated with lg urinary albumin/creatinine ratio, lg cardiac troponin T, lg N-terminal pro-B type natriuretic peptide, and heart rate; RHI is positively correlated with CFR.Conclusions:The prevalence of CMD and MED in nHFrEF patients is high, and the two have a certain positive correlation. Increased heart rate and RHI are risk and protective factors for CMD, respectively, while increased CFR is a protective factor for MED. MED may be a potential therapeutic target for nHFrEF patients.

Objective:To investigate the sleep characteristics and executive function development in children aged 6-12 years with attention deficit hyperactivity disorder(ADHD),and to examine the relationship between them.Methods:A total of 112 children diagnosed with ADHD according to the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ),and 45 age-and gender-matched typically developing children were recruited.Sleep characteristics were assessed with the Chinese version of Children's Sleep Habits Questionnaire(CSHQ)and ActiGraph GT9X Link Three-axis acceleration body dynamometert.Core ADHD symptoms and multi-ple dimensions of executive function were evaluated withthe Swanson,Nolan,and Pelham scale,Fourth Edition(SNAP-Ⅳ)assessment scale,Stroop Color-Word Test(SCWT),Rey-Osterrieth Complex Figure Test(ROCFT),and Trail Making Test(TMT).Results:Compared with controls,children with ADHD showed significantly higher total CSHQ scores,sleep resistance,sleep anxiety,and sleep maintenance time(P＜0.05),and had significantly lower sleep efficiencies measured by ActiGraph GT9X Link(P＜0.05).In the SCWT,children with ADHD re-quired more time in the word interference and color interference tests(P＜0.05).In the ROCFT,the scores of im-mediate details,delayed details,immediate structure,and delayed structure were lower in the children with ADHD(P＜0.05).In the TMT,the number of errors in the digit connection and the time and number of errors in the digit-letter connection were higher in the children with ADHD(P＜0.05).The total CSHQ scores of ADHD children were negatively correlated with the working memory scores and positively correlated with the core symptom scores.Conclusion:Children with ADHD exhibit notable sleep disturbance and underdeveloped executive func-tion.the sleep problems,as measured by CSHQ are associated significantly with deficits in executive function.

ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.