To assess the implantation effectiveness of porous scaffolds, it is essential to consider not only their mechanical properties but also their biological performance. Given the high cost, long duration and low reproducibility of biological experiments, simulation studies as a virtual alternative, have become a widely adopted and efficient evaluation method. In this study, based on the secondary development environment of finite element analysis software, the strain energy density growth criterion for bone tissue was introduced to simulate and analyze the cell proliferation-promoting effects of four different lattice porous scaffolds under cyclic compressive loading. The biological performance of these scaffolds was evaluated accordingly. The computational results indicated that in the early stages of bone growth, the differences in bone tissue formation among the scaffold groups were not significant. However, as bone growth progressed, the scaffold with a porosity of 70% and a pore size of 900 μm demonstrated markedly superior bone formation compared to other porosity groups and pore size groups. These results suggested that the scaffold with a porosity of 70% and a pore size of 900 μm was most conducive to bone tissue growth and could be regarded as the optimal structural parameter for bone repair scaffold. In conclusion, this study used a visualized simulation approach to pre-evaluate the osteogenic potential of porous scaffolds, aiming to provide reliable data support for the optimized design and clinical application of implantable scaffolds.
Tissue Scaffolds/chemistry* ; Porosity ; Finite Element Analysis ; Tissue Engineering/methods* ; Computer Simulation ; Bone Development ; Osteogenesis ; Humans ; Cell Proliferation

Objective:To explore the value of contrast-enhaoced echocardiography for measuring pulmonary transit time（PTT）in assessing heart failure after percutaneous coronary intervention（PCI）in acute ST-segment elevation myocardial infarction（STEMI）patients.Methods:From September 2023 to September 2024，120 patients with STEMI undergoing PCI at Hunan Provincial People's Hospital were prospectively selected and divided into a heart failure group（ n=42）and a non-heart failure group（ n=78）according to the guidelines. The differences in general clinical data，laboratory parameters，and echocardiographic parameters between the two groups were compared. The diagnostic efficacies of PTT，normalized PTT（nPTT），and N-terminal pro-B-type natriuretic peptide（NT-proBNP）were analyzed. Consistency between them and New York Heart Association（NYHA）heart function classification was tested. Results:Compared to the non-heart failure group，the NT-proBNP，PTT，and nPTT values in the heart failure group were significantly increased（all P<0.05）. The area under the curve（AUC）of nPTT was 0.944，better than that of PTT and NT-proBNP（AUC=0.871，0.887）. After K-means clustering reclassified patients into four levels based on nPTT values，nPTT classification showed moderate consistency with NYHA classification（Kappa=0.580， P<0.001），and nPTT differed significantly across NYHA classifications（ P<0.05）. Conclusions:PTT，as an echocardiographic index for assessing cardiac function，has similar diagnostic efficacy to NT-proBNP，the nPTT is even better. It shows moderate consistency with the NYHA classification and holds potential for differentiating overlapping NYHA grades. Importantly，it offers a fresh objective way to evaluate cardiac dysfunction after PCI in STEMI patients.

OBJECTIVE To explore the risk factors for postoperative infectious endophthalmitis,distribution of pathogens and peripheral blood interleukin-17(IL-17),matrix metalloproteinase-2(MMP-2)and insulin-like growth factor-1(IGF-1)in the patients with cataract and analyze the significance.METHODS A total of 60,000 patients with cataract who received surgical procedures in Daqing Eye Hospital from Jan.2018 to Jun.2024 were recruited as the research subjects.The aqueous humor and vitreous humor were collected from the patients with postoperative infectious endophthalmitis,and the isolated pathogens were identified.The baseline data were com-pared,the risk factors for the infectious endophthalmitis were analyzed.The levels of serum IL-17,MMP-2 and IGF-1 were compared,and the efficiencies of the indexes in prediction of infectious endophthalmitis were analyzed.RESULTS Totally 65,600 eyes involving 60,000 patients were enrolled in the study,21 of which(21 patients)were diagnosed with infectious endophthalmitis,with the incidence rate 0.032％.All of the 21 eyes were cultured positive for pathogens,among which gram-positive bacteria(73.08％)were dominant.Univariate analysis and multivariate analysis showed that complication with diabetes mellitus and vitreous overflow were the risk factors for the postoperative infectious endophthalmitis in the cataract patients.There were significant differences in the levels of serum IL-7,MMP-2 and IGF-1 between the infection group and the non-infection group after the surgery for 3 days(P＜0.05).Receiver operating characteristic(ROC)curve analysis showed that the levels of serum IL-17,MMP-2 and IGF-1 after the surgery for 3 days could predict the occurrence of postoperative infectious endoph-thalmitis in the cataract patients,and the joint detection of the three indexes has highest predictive efficiency(P＜0.05),the area under the curve was 0.950,with the sensitivity 95.24％,the specificity 81.91％.CONCLUSIONS The incidence rate of postoperative endophthalmitis is 0.032％among the cataract patients.The complication with diabetes mellitus and vitreous outflow are the risk factors.The gram-positive bacteria are dominant among the pathogens.The changes of serum IL-17,MMP-2 and IGF-1 levels are closely associated with the occurrence of en-dophthalmitis,which has predictive value.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective:To investigate the difference in intracranial infection rate between long-tunneled external ventricular drainage(LTEVD)and conventional external ventricular drainage(EVD),as well as the risk factors for intracranial infection.Methods:A retro-spective analysis was performed for the clinical data of 45 patients who were admitted to Department of Neurology Center,The Third Affiliated Hospital of Chongqing Medical University,from January 2020 to December 2022 and underwent EVD,among whom 13 patients underwent LTEVD(LTEVD group)and 32 patients underwent conventional EVD(EVD group).Related data were recorded for both groups,including general information,postoperative catheter-related complications,and postoperative management,to investi-gate the effect on reducing the rate of intracranial infection.According to the presence or absence of intracranial infection after surgery,the patients were divided into the infection group with 10 patients and non-infection group with 35 patients,and related clini-cal data were analyzed to investigate the risk factors for intracranial infection.Results:The LTEVD group had a significantly lower secondary infection rate of catheterization days than the EVD group[2.40‰(1/417)vs.27.19‰(9/331),P=0.009].The duration of catheterization was 14-85 days[27.00(22.50,36.50)days]in the LTEVD group and 8-22 days[9.00(8.00,11.50)days]in the EVD group,suggesting that the LTEVD group had a significantly longer duration of catheterization than the EVD group(P=0.000).The multivariate logistic regression analysis showed that the times of cerebrospinal fluid sampling was an independent risk factor for post-operative intracranial infection in patients undergoing EVD,and the use of LTEVD was a protective factor against intracranial infection after EVD.Conclusion:Compared with conventional EVD,LTEVD can safely prolong the duration of catheterization and reduce the rate of postoperative intracranial infection in patients undergoing EVD.The use of LTEVD procedure and the reduction in the times of cerebrospinal fluid sampling can reduce the risk of postoperative in-tracranial infection.

Objective To explore the interaction between long non-coding RNA growth arrest-specific 5(GAS5)and miR-135b-5p/adenomatous polyposis coli(APC)axis,and to elucidate its biological function in the proliferation,metastasis and invasion of glioma.Methods The relationship of GAS5 expression level with survival rate of glioma patients was analyzed based on CGGA database.qRT-PCR was used to detect the expression level of GAS5 in glioma tissues and cell lines.Human glioma T98 and A172 cell lines were subjected for overexpression and knockdown of GAS5,miR-135b-5p and APC by transfection.Western blotting and qRT-PCR were applied to measure the expression of related genes in glioma tissues or cell lines.CCK-8,Transwell and wound healing assays was conducted to determine the effect of GAS5 on the viability and motility of glioma cells.Moreover,dual luciferase reporter analysis were utilized to elucidate the regulatory mechanisms of GAS5 and miR-135b-5p/APC.Results Analysis on CGGA database showed that the survival rate of glioma patients with low GAS5 expression was significantly decreased(P＜0.001).Western blotting and qRT-PCR indicated that GAS5 was down-regulated in the glioma cell lines and tissues than human normal astrocytes and para-cancer tissues(P＜0.01).The results of CCK-8,Transwell and wound healing assays revealed that overexpression of GAS5 significantly inhibited the viability,invasion and migration abilities in T98 cells when compared with the cells of the vector group(P＜0.01).Dual luciferase reporter analysis displayed that there were binding sites between GAS5 and miR-135b-5p,and the expression of the two was negatively correlated(P=0.019).Further studies suggested that the effect of GAS5 on biological function in glioma cells was through targeting miR-135b-5p,and overexpression of APC reversed the promoting effect of miR-135b-5p on glioma cells(P＜0.01).Western blotting displayed that enhancing miR-135b-5p expression inhibited the expression of APC(P＜0.001),and GAS5 upregulated the expression of APC by targeting miR-135b-5p(P＜0.01).Conclusion GAS5 inhibits the progression of glioma via miR-135b-5p/APC axis,which revealing the molecular regulatory mechanism of GAS5/miR-135b-5p/APC.

Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.

Objective:Periprosthetic joint infection (PJI) is one of the most severe complications following hip and knee arthroplasty and is a leading cause of revision surgery. Pathogens and their antibiotic susceptibility are key factors in the successful treatment of PJI. This study retrospectively analyzes the pathogen characteristics and antimicrobial susceptibility of PJI patients treated at our center, aiming to establish an empirical antibiotic regimen for PJI in the region, providing a reference for empirical antibiotic therapy in the clinical management of PJI.Methods:This study retrospectively reviewed PJI patients treated at our center from January 2018 to October 2024. In each case, preoperative arthrocentesis fluid, and synovium tissue from at least three sites during surgery were collected for aerobic and anaerobic blood culture. The positive culture rate, distribution of pathogens based on Gram staining, methicillin resistance, mixed infections, and multidrug resistance were analyzed. Effective coverage parameters were constructed based on antimicrobial sensitivity and coverage rates, and appropriate empirical antimicrobial regimens were proposed.Results:A total of 233 PJI patients were included in the analysis. There were 99 males and 134 females with an average age of 67.0±10.1 years (ranging from 32 to 93 years). The study included 130 hip and 103 knee arthroplasty patients. Among the patients, 202 (86.7%) had positive cultures, with a total of 301 pathogen strains isolated: 268 Gram-positive bacteria (89.4%), 25 Gram-negative bacteria (8.3%), and 7 fungal strains (2.3%). The most common Gram-positive bacteria were coagulase-negative staphylococci (196 strains, 65.1%), epidermal staphylococci (77 strains, 25.6%), Staphylococcus aureus (39 strains, 13.0%), and Streptococcus spp. (19 strains, 6.3%). The most common Gram-negative bacteria were Enterobacteriaceae (14 strains, 4.7%). In hip joint infections, the most prevalent pathogens were epidermal Staphylococci (48 strains, 28.1%) and Staphylococcus aureus (27 strains, 15.8%), while in knee joint infections, epidermal Staphylococci (29 strains, 22.3%) were most common. Regarding antibiotic resistance, 48.5% of staphylococcal strains were methicillin-resistant Staphylococcus, and 51.5% were multidrug-resistant strains. Staphylococci were 100% susceptible to vancomycin, teicoplanin, daptomycin, linezolid, and tigecycline, but exhibited high resistance to β-lactams and quinolone antibiotics. Analysis of empirical antibiotic regimens revealed that vancomycin combined with meropenem, linezolid combined with meropenem, vancomycin combined with imipenem, vancomycin combined with piperacillin/tazobactam, and vancomycin combined with ceftriaxone had effective coverage rates of 97.0%, 97.0%, 96.0%, 94.9%, and 90.9%, respectively.Conclusion:The main pathogens in PJI in this region are Gram-positive bacteria, with high rates of methicillin resistance and multidrug resistance. Based on antimicrobial susceptibility data, we recommend vancomycin combined with meropenem as the empirical treatment regimen for culture-negative PJI in this region, with linezolid combined with meropenem as an alternative.

Objective:To screen broadly neutralizing antibodies in human immunodeficiency virus-1（HIV-1）chronically infected individuals and characterize their molecular features and to provide new strategies for rational vaccine development and antibody-based therapeutics.Methods:A total of 34 treatment-na?ve individuals with chronic HIV-1 infection were enrolled. Plasma antibody binding levels were measured against two HIV-1 envelope proteins. Single antigen-specific memory B cells were sorted from high-binding samples，and antibody variable region genes were amplified by PCR for paired expression. The monoclonal antibodies were evaluated for neutralizing activity using pseudovirus assays，and their structural features were analyzed by integrating AlphaFold 3 prediction with Discovery Studio molecular docking.Results:Plasma samples showed strong binding to DU422-GP140 and BG505-GP140. Eight monoclonal antibodies were isolated from two donors. Among them，antibodies 0919-A4，0919-A9 and 0808-A2 could cross-react with GP140 from HIV-1 subtypes AE，BC and B. The monoclonal antibody 0919-A9 demonstrated potent neutralizing activity against SF162（Tier 1）and CH181（Tier 2）pseudoviruses，with somatic hypermutation rates of 13.27%（heavy chain）and 15.58%（light chain）. Structural modeling revealed its specific targeting of the V1V2 region on GP120.Conclusion:The isolated antibody 0919-A9 effectively neutralizes Tier 2 pseudoviruses. Its high somatic mutation frequency and V1V2-targeting property underlie its neutralizing activity，providing both a promising candidate and mechanistic insights for HIV vaccine development and antibody-based therapeutic strategies.