ObjectiveThe controllability changes of structural brain network were explored based on the control and brain network theory in young smokers, this may reveal that the controllability indicators can serve as a powerful factor to predict the sleep status in young smokers. MethodsFifty young smokers and 51 healthy controls from Inner Mongolia University of Science and Technology were enrolled. Diffusion tensor imaging (DTI) was used to construct structural brain network based on fractional anisotropy (FA) weight matrix. According to the control and brain network theory, the average controllability and the modal controllability were calculated. Two-sample t-test was used to compare the differences between the groups and Pearson correlation analysis to examine the correlation between significant average controllability and modal controllability with Fagerström Test of Nicotine Dependence (FTND) in young smokers. The nodes with the controllability score in the top 10% were selected as the super-controllers. Finally, we used BP neural network to predict the Pittsburgh Sleep Quality Index (PSQI) in young smokers. ResultsThe average controllability of dorsolateral superior frontal gyrus, supplementary motor area, lenticular nucleus putamen, and lenticular nucleus pallidum, and the modal controllability of orbital inferior frontal gyrus, supplementary motor area, gyrus rectus, and posterior cingulate gyrus in the young smokers’ group, were all significantly different from those of the healthy controls group (P<0.05). The average controllability of the right supplementary motor area (SMA.R) in the young smokers group was positively correlated with FTND (r=0.393 0, P=0.004 8), while modal controllability was negatively correlated with FTND (r=-0.330 1, P=0.019 2). ConclusionThe controllability of structural brain network in young smokers is abnormal. which may serve as an indicator to predict sleep condition. It may provide the imaging evidence for evaluating the cognitive function impairment in young smokers.

Objective To investigate the regulatory effect and molecular mechanism of circ_0044556 on the malignant biological behavior of triple negative breast cancer(TNBC)cells by targeting the miR-338-3p/bromodomain-containing protein 4(BRD4)axis.Methods The TargetScan online website was used to predict the binding sites of circ_0044556 with miR-338-3p and miR-338-3p with BRD4.Dual-luciferase reporter gene assays were performed to determine the relationship among circ_0044556,miR-338-3p,and BRD4 in MDA-MB-231 cells.Quantitative real-time PCR(qRT-PCR)and Western blotting were employed to detect the expression of circ_0044556,miR-338-3p,and BRD4 protein in human TNBC cell line MDA-MB-231 and human normal breast epithelial cells MCF-10A.MDA-MB-231 cells were divided into NC group,si-NC group(transfected with si-NC),si-circ_0044556 group(transfected with si-circ_0044556),si-circ_0044556+inhibitor NC group(transfected with si-circ_0044556 and inhibitor NC),and si-circ_0044556+miR-338-3p inhibitor group(transfected with si-circ_0044556 andmiR-338-3p inhibitor).qRT-PCR was applied to detect the expression of circ_0044556 and miR-338-3p;Western blotting was used to detect the expression of BRD4,E-cadherin,N-cadherin and Vimentin;the CCK-8 assay was applied to detect cell proliferation;flow cytometry was applied to detect cell apoptosis;and Transwell assays were used to detect cell invasion and migration.Thirty nude mice were randomly divided into NC group(tail vein injection of normal saline),si-NC group(tail vein injection of LV-NC),si-circ_0044556 group(tail vein injection of LV-circ_0044556),si-circ_0044556+inhibitor NC group(tail vein injection of LV-circ_0044556 and antiagomir NC),and si-circ_0044556+miR-338-3p inhibitor group(tail vein injection of LV-circ_0044556 and antiagomir miR-338-3p),with 6 mice per group.A xenograft tumor model was constructed by subcutaneous injection of MDA-MB-231 cells into nude mice,and tumor volume and weight were measured.Results TargetScan prediction results showed that the downstream miRNA of circ_0044556 was miR-338-3p,and the downstream target gene of miR-338-3p might be BRD4.Compared with transfecting mimic NC,transfection with miR-338-3p mimic significantly reduced the luciferase activities of WT-circ_0044556(0.34±0.03 vs.1.00±0.15,P<0.05)and WT-BRD4(0.41±0.05 vs.1.05±0.13,P<0.05)in MDA-MB-231 cells.Compared with MCF-10A cells,the expression levels of circ_0044556 and BRD4 protein in MDA-MB-231 cells were significantly increased,while the expression level of miR-338-3p was significantly decreased(P<0.05).Compared with NC group and si-NC group,the expression levels of circ_0044556,the protein expression levels of BRD4,N-cadherin,and Vimentin,and the OD450 value in MDA-MB-231 cells of si-circ_0044556 group and si-circ_0044556+inhibitor NC group were significantly decreased(P<0.05),the number of migrated and invaded cells was significantly reduced(P<0.05),and the expression level of miR-338-3p,the protein expression level of E-cadherin,and the cell apoptosis rate in MDA-MB-231 cells were significantly increased(P<0.05);downregulation of miR-338-3p rescued the inhibitory effect of circ_0044556 knockdown on invasion,migration,and proliferation of MDA-MB-231 cells.Compared with NC group and si-NC group,the tumor volume and weight in si-circ_0044556 group and si-circ_0044556+inhibitor NC group were significantly decreased(P<0.05);compared with si-circ_0044556 group and si-circ_0044556+inhibitor NC group,the tumor volume and weight in si-circ_0044556+miR-338-3p inhibitor group were significantly increased(P<0.05).Conclusion circ_0044556 may promote the malignant biological behaviors of TNBC cells through the miR-338-3p/BRD4 axis.

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

Objective To investigate the correlation between dual-energy computed tomography angiography(CTA)parameters of carotid plaques and acute stroke events.Methods A retrospective analysis was conducted on the clinical and imaging data of patients who underwent dual-energy head and neck CTA and brain MRI scans.Utilizing the Siemens workstation(Syngo.Via VB40B),region of interest(ROI)were placed on the thickest slice of the carotid plaque in the axial plane to obtain parameters such as fat fraction(FF),virtual non-contrast(VNC)value,iodine concentration(IC),electron density(Rho),effective atomic number(Zeff),dual energy index(DEI),spectral curve,and corresponding CT values at 40 keV(40 keVHU)and 90 keV(90 keVHU).The slope of the energy spectrum curve(λ)was calculated within the 40 keV-90 keV range.Patients with acute cerebral infarction(ACI)in the ipsilateral anterior circulation territory were classified into the ACI group,while those without were classified into the non-acute cerebral infarction(NACI)(NACI group).Qualitative data were analyzed using the x2 test,and quantitative data were analyzed using the t-test.The predictive performance was assessed using the area under the curve(AUC)of the receiver operating characteristic(ROC)curve,and the differences between different ROC curves were compared using the DeLong test.Results A total of 72 patients were included,with 21 in the ACI group and 51 in the NACI group.The mean values of FF,Zeff,and 40 keVHU in the ACI group were greater than those in the NACI group.Statistically significant differences were observed between the groups for Zeff,DEI,40 keVHU,and λ(P＜0.05).40 keVHU demonstrated the highest predictive performance,and the AUC,sensitivity,and specificity was 0.789,81.0％,and 74.5％,respectively.A combined variable constructed through logistic regression analysis yielded an AUC,sensitivity,and specificity of 0.796,85.7％,and 70.6％,respectively,with no significant statistical differences compared to single factor variables.Conclusion Dual-energy CTA parameters of carotid plaques may aid in predicting intraplaque hemorrhage(IPH)and the occurrence of acute stroke events.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective To investigate the effect of intravenous injection of remifentanil on the comfort level of birth-giving women with scarred uterus undergoing cesarean section.Methods A total of 82 birth-giving women with scarred uterus who underwent cesarean section in the Suqian Hospital of Jiangsu Provincial People's Hospital from October 2021 to September 2023 were selected and randomly divided into the observation group and the control group(with 41 cases in each group).Before skin resection of cesarean section,the birth-giving women of the observation group were injected with 0.05 μg·kg-1·min-1 remifentanil intravenously until the end of the operation,and these in the control group was injected with the same amount of normal saline.The vital signs and pain at different time points,traction reaction and occurrence of maternal and infant complications were compared between the two groups.Results The mean arterial pressure(MAP),heart rate(HR),pain visual analogue scale(VAS)score and incidence of traction reactions at abdominal exploration in the observation group were significantly lower than those in the control group(P<0.05).There was no significant difference in the neonatal umbilical vein pH value,umbilical vein blood pulse oximetry saturation(SPO2),Apgar scores 1 minute and 5 minutes after birth of newborn,or nausea,vomiting and respiratory depression of birth-giving women between the two groups(P>0.05).Conclusion For birth-giving women with scar uterus who underwent cesarean section,intravenous injection of 0.05 μg·kg-1·min-1 of reifentanil can reduce the fluctuation of vital signs,significantly relieve the traction reaction at abdominal exploration,with a few maternal and infant complications,which is conducive to improving the comfort level of the birth-giving women.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.