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 identify the key features of facial and tongue images associated with anemia in female populations, establish anemia risk-screening models, and evaluate their performance. METHODS: A total of 533 female participants (anemic and healthy) were recruited from Shuguang Hospital. Facial and tongue images were collected using the TFDA-1 tongue and face diagnosis instrument. Color and texture features from various parts of facial and tongue images were extracted using Face Diagnosis Analysis System (FDAS) and Tongue Diagnosis Analysis System version 2.0 (TDAS v2.0). Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for feature selection. Ten machine learning models and one deep learning model (ResNet50V2 + Conv1D) were developed and evaluated. RESULTS: Anemic women showed lower a-values, higher L- and b-values across all age groups. Texture features analysis showed that women aged 30-39 with anemia had higher angular second moment (ASM)and lower entropy (ENT) values in facial images, while those aged 40-49 had lower contrast (CON), ENT, and MEAN values in tongue images but higher ASM. Anemic women exhibited age-related trends similar to healthy women, with decreasing L-values and increasing a-, b-, and ASM-values. LASSO identified 19 key features from 62. Among classifiers, the Artificial Neural Network (ANN) model achieved the best performance [area under the curve (AUC): 0.849, accuracy: 0.781]. The ResNet50V2 model achieved comparable results [AUC: 0.846, accuracy: 0.818]. CONCLUSION Differences in facial and tongue images suggest that color and texture features can serve as potential TCM phenotype and auxiliary diagnostic indicators for female anemia.
Humans ; Female ; Tongue/diagnostic imaging* ; Adult ; Anemia/diagnosis* ; Middle Aged ; Face/diagnostic imaging* ; Young Adult ; Machine Learning

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective To study the influences of the structural parameters of the pump head flow channel on the energy dissipation of injection pumps and optimize the pump head flow channel structural parameters.Methods Firstly,three structural parameters of the injection pump head flow channel,namely the input chamber diameter,the connecting chamber diameter and the plunger rod chamber diameter,were selected as the experimental factors for orthogonal experimental design,and the total entropy production values of the injection pump head flow channels with different structures were obtained through entropy production analysis;secondly,the effects of the three structural parameters on the total entropy production values were explored with the range method;finally,the Kriging interpolation proxy model analysis and computational fluid dynamics(CFD)numerical analysis of the injection pump head flow channel were carried out to determine the effects of the combinations of the three structural parameters by pairs on the total entropy production values,and the structural parameters of the injection pump head flow channel were optimized with the objective of energy dissipation.Results The minimum total entropy production value was 2 783 970 mW/K,which was 29.8%lower than that in case of the initial structure(3 966 072 mW/K),when the input chamber diameter was 4.8 mm,the connecting chamber diameter was 0.32 mm and the plunger rod chamber diameter was 1.0 mm;the three structural parameters had significant differences in the effects on the total entropy production value,ordered as the plunger rod chamber diameter,the input chamber diameter and the connecting chamber diameter;considering the energy dissipation,the total entropy production value was minimized in case of the minimal input chamber diameter,the maximal connecting chamber diameter and the medium-sized plunger rod chamber diameter.Conclusion The input chamber diameter,the connecting chamber diameter and the plunger rod chamber diameter have differences in the sensitivity to the effects on the energy dissipation of the injection pump head flow channel,and the structural parameters of the head flow path can be optimized accordingly with the goal of minimizing energy dissipation.[Chinese Medical Equipment Journal,2025,46(9):28-32]

OBJECTIVE To investigate the protective effect and mechanism of saikosaponin C(SSC)on acute liver injury(ALI)in mice induced by carbon tetrachloride(CCl4)based on serum metabolomics.METHODS Forty mice were divided into blank group(water),model group(water),positive control drug group(Biphenyl diester drop pills,150 mg/kg),and SSC low-and high-dose groups(2.5,10 mg/kg)using the random number table method,with 8 mice in each group.They were given water/relevant drugs,once a day,for 7 consecutive days.One hour after the last administration,all mice were intraperitoneally injected with 0.2％CCl4 olive oil to induce ALI model,except for the blank group.After 17 hours of the modeling,the liver index of mice was calculated.The levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),lactate dehydrogenase(LDH),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-1β in serum of mice were detected.The histopathological changes of liver tissue were observed.Meanwhile,the serum metabolomics of mice were analyzed by liquid chromatography-mass spectrometry.RESULTS Compared with the blank group,the levels of liver index,ALT,AST,LDH,TNF-α,IL-6,and IL-1β in the model group were significantly increased(P＜0.01).Hepatocytes were edema,vacuolar degeneration,more necrosis,and a large number of inflammatory cells were infiltrated.Compared with the model group,liver index and serum index levels of mice were significantly decreased(P＜0.05 or P＜0.01),accompanied by marked improvement in histopathological damage to the liver tissue.The metabolomics results showed that compared with the model group,there were 63 up-regulated and 256 down-regulated differential metabolites in the serum of mice in the SSC high-dose group,including prostaglandin B2,20-hydroxy-leukotriene B4,5-hydroxy-L-tryptophan,7α-hydroxycholesterol,etc.;these metabolites were primarily involved in metabolic pathways such as arachidonic acid metabolism,5-hydroxytryptamine synapse,primary bile acid biosynthesis.CONCLUSIONS SSC exerts a protective effect against CCl4-induced ALI by down-regulating the level of key metabolites such as prostaglandin B2 and 20-hydroxy-leukotriene B4,and then ruducing metabolic pathways such as arachidonic acid metabolism,5-hydroxytryptamine synapse,and primary bile acid biosynthesis.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective To study the influences of the structural parameters of the pump head flow channel on the energy dissipation of injection pumps and optimize the pump head flow channel structural parameters.Methods Firstly,three structural parameters of the injection pump head flow channel,namely the input chamber diameter,the connecting chamber diameter and the plunger rod chamber diameter,were selected as the experimental factors for orthogonal experimental design,and the total entropy production values of the injection pump head flow channels with different structures were obtained through entropy production analysis;secondly,the effects of the three structural parameters on the total entropy production values were explored with the range method;finally,the Kriging interpolation proxy model analysis and computational fluid dynamics(CFD)numerical analysis of the injection pump head flow channel were carried out to determine the effects of the combinations of the three structural parameters by pairs on the total entropy production values,and the structural parameters of the injection pump head flow channel were optimized with the objective of energy dissipation.Results The minimum total entropy production value was 2 783 970 mW/K,which was 29.8%lower than that in case of the initial structure(3 966 072 mW/K),when the input chamber diameter was 4.8 mm,the connecting chamber diameter was 0.32 mm and the plunger rod chamber diameter was 1.0 mm;the three structural parameters had significant differences in the effects on the total entropy production value,ordered as the plunger rod chamber diameter,the input chamber diameter and the connecting chamber diameter;considering the energy dissipation,the total entropy production value was minimized in case of the minimal input chamber diameter,the maximal connecting chamber diameter and the medium-sized plunger rod chamber diameter.Conclusion The input chamber diameter,the connecting chamber diameter and the plunger rod chamber diameter have differences in the sensitivity to the effects on the energy dissipation of the injection pump head flow channel,and the structural parameters of the head flow path can be optimized accordingly with the goal of minimizing energy dissipation.[Chinese Medical Equipment Journal,2025,46(9):28-32]

Objective To evaluate the efficacy of surgery,chemotherapy and surgery combined chemotherapy for retinoblastoma(RB),and analyze the prognostic factors of RB patients.Methods Clinical data of 1188 RB patients registered in the Surveillance,Epidemiology and End Results(SEER)database from January 2000 to December 2019 were retrospectively analyzed.The baseline characteristics of patients treated with surgery,chemotherapy or surgery combined with chemotherapy were balanced by inverse probability of treatment weighting(IPTW).Log-rank test analysis was used to compare the survival probability of patients in the 3 groups,and Cox regression models were used to analyse the factors influencing the prognosis of RB patients.Results A total of 1188 RB cases were included in this study,including 426 cases in surgery group,200 cases in chemotherapy group and 562 cases in surgery combined with chemotherapy group.After IPTW weighting,baseline data such as age,sex and race were balanced(P＞0.05).Log-rank test results showed that the survival curves of the three groups were significantly different before and after weighting(P＜0.05).After weighted,the survival of patients in surgery group was significantly better than that in chemotherapy group and surgery combined chemotherapy group(P＜0.05),and there was no statistical significance between chemotherapy group and surgery combined chemotherapy group(P＞0.05).The weighted patient survival probability at 1st,3rd and 5th years were 99.7%,98.9%and 98.6%in surgery group;97.4%,95.8%and 95.8%in chemotherapy group;and 97.9%,95.8%and 95.0%in surgery combined chemotherapy group.Cox regression analysis showed that compared with surgery group,the specific risk ratio of death was 1.367(95%CI 1.100-1.700)in chemotherapy group and 1.132(95%CI 0.963-1.330)in combined chemotherapy group.Compared with patients with 1 RB lesion,the patient-specific mortality risk ratio for patients with 2 or more RB lesions was 0.399(95%CI 0.268-0.594).Conclusions Patients with RB have higher survival rates probability after treatment.After controlling the influence of age,sex and other factors,the effect of surgery was better among the three treatment methods.Multifocality may be an independent prognostic factor in RB patients.

Acute liver injury (ALI) is one of the common severe diseases in clinic, which is characterized by redox imbalance and inflammatory storm. Untimely treatment can easily lead to liver failure and even death. Rosmarinic acid (RA) has been proved to have anti-inflammatory and antioxidant activity, but it is not clear how to protect ALI through antioxidation and inhibition of inflammation. Therefore, this study explored the therapeutic effect and molecular mechanism of RA on ALI through in vitro and in vivo experiments. In the mouse ALI model, the effects of RA on liver function and inflammatory indexes were studied, the pathological changes of liver were observed by HE, the effect of RA on reactive oxygen species in liver was detected by fluorescence method, and the level of F4/80 in liver tissue was detected by immunohistochemical method. The levels of thioredoxin interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3) and cysteinyl aspartate specific proteinase-1 (CASPASE-1) in liver tissue were measured by Western blot. All animal welfare and experimental procedures follow the rules of the Animal Ethics Committee of Southwest Minzu University. In vitro, human hepatoma cell line HepG2 was used to establish the model of oxidative damage induced by H₂O₂. The cell viability was detected by CCK-8 method. The level of interleukin-1β (IL-1β) in the supernatant was detected by enzyme linked immunosorbent assay (ELISA), the activity of lactatede hydrogenase (LDH) was detected by LDH kit, and the level of ROS was detected by fluorescence probe DCFH-DA labeling. The mRNA expression of Txnip, Nlrp3, Caspase 1, Il1β was detected by real-time fluorescence quantitative PCR (qPCR), and the protein levels of nuclear factor erythroid-2 related factor 2 (NRF2), TXNIP, NLRP3 and CASPASE-1 were measured by Western blot. The results showed that compared with the model group, the degree of liver swelling, tissue injury, liver function index in RA group were significantly lower than those in model group. And RA significantly attenuated the increases of ROS in liver tissue. The expression levels of TXNIP, NLRP3 and CASPASE-1 in liver tissue were significantly lower than those in model group. Additionally, RA inhibited the expressions of F4/80 and IL-1β. In vitro experiment, compared with model group, RA effectively inhibited the secretion of IL-1β and LDH. The level of ROS also decreased significantly. RA inhibited the mRNA expressions of Txnip, Caspase 1, Il1β. Furthermore, RA significantly increased the expression level of NRF2 protein in nucleus, and decreased the expression level of TXNIP and NLRP3 protein. Specifically, with the addition of ML385, the effect of RA on NRF2, TXNIP, NLRP3, CASPASE-1 protein expression was reversed. Collectively, these findings suggested that RA may inhibit the production of ROS by promoting NRF2 nuclear transfer, and then reduce the activation of NLRP3 inflammatory bodies by TXNIP, reduce cell death and inflammatory response to prevent the liver injury.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.