Objectives:To explore the predictive value of residual Murray's law-based quantitative flow ratio(μQFR)on long-term vessel-oriented composite endpoints(VoCE).Methods:This retrospective study included 3 510 patients from the FAVOR Ⅲ China trial.Offline residual μQFR analysis was performed on all vessels(diameter≥2.5 mm)with 50%-90%stenotic lesions.Patients were stratified into high-,intermediate-,and low-risk groups based on residual μQFR tertiles.The primary endpoint was 3-year VoCE,defined as a composite of cardiac death related to the target vessel,target vessel-related spontaneous myocardial infarction,and ischemia-driven target vessel revascularization.Results:Offline analysis was performed on 5 256 vessels from 3 510 patients.The mean residual μQFR was 0.92±0.75.The high-risk group(residual μQFR≤0.91)with 1 554 patients(1 958 vessels);the intermediate-risk group(residual μQFR 0.92-0.96)with 1 211 patients(1 906 vessels);and the low-risk group(residual μQFR>0.96)with 745 patients(1 392 vessels).Over 3-year follow-up,VoCE occurred in 227 vessels(4.3%).The 3-year VoCE incidence was significantly higher in the high-risk group compared to the intermediate-and low-risk groups(6.2%vs.4.1%vs.2.5%,log-rank P<0.001),primarily driven by ischemia-driven target vessel revascularization(5.0%vs.3.0%vs.1.6%,log-rank P<0.001).Hypertension(OR=0.83,95%CI:0.72-0.96),hypercholesterolemia(OR=0.84,95%CI:0.73-0.97),bifurcation lesions(OR=0.72,95%CI:0.63-0.83),moderate/severe calcification(OR=0.70,95%CI:0.57-0.84),and tandem lesions(OR=0.59,95%CI:0.47-0.75)were independent predictors of lower residual μQFR values.Conclusions:Lower residual μQFR is significantly associated with increased VoCE risk during the 3-year follow up period.

Objective:To investigate the role and mechanism of TrxR1 in reprogramming tumor-associated macrophage in breast cancer,providing novel insights and theoretical foundations for clinical breast cancer treatment.Methods:TISIDB database was used to analyze the relationship between TXNRD1(encoding TrxR1)and tumor immunity.Mouse breast cancer 4T1 cells conditioned medium was collected and co-cultured with bone marrow-derived macrophage(BMDM)cells for 48 h to detect the expression of macrophage immunosuppression-related factors.TrxR1 secretion by tumor cells was measured using ELISA kits.TXNRD1 knockdown efficiency was verified via Western blot.Fluorescence quantitative PCR(qPCR)and flow cytometry were used to detect the expression levels of macrophage immunosuppressive factors after TXNRD1 knockdown in tumor cells.JASPAR database was used to analyze the potential regulatory factors,and Western blot was used to verify the expression of pathway-related proteins.Results:Database analysis found that TXNRD1 expression positively correlated with survival risk indices across multiple cancers,with the strongest association observed in breast cancer.Further analysis found that elevated TXNRD1 expression correlated with reduced infiltration of M1 macrophages and natural killer(NK)cells,but increased M2 macrophage infiltration.qPCR and flow cytometry demonstrated that tumor-conditioned medium enhanced macrophage immunosuppression,whereas medium from TXNRD1-knockdown tumor cells suppressed this effect.And TrxR1-neutralizing antibodies could also reversed this effect.JASPAR database analysis identified STAT3 and STAT6 as potential transcriptional regulators,and Western blot confirmed that TXNRD1-knockdown tumor cells conditioned medium inhibited STAT6 pathway activation in macrophages.Conclusion:In the tumor microenvironment,breast tumor-derived TrxR1 promotes macrophage immunosuppression,potentially through activation of the STAT6 signaling pathway.

Objective Using network pharmacology research methods and animal pharmacology experiments,explore the mechanism of antidepressant effects of traditional Chinese medicine Citron and Bergamot.Methods Using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),ETCM,Symmap,Swiss Target Prediction,and Uniprot data platforms,screen the active ingredients and corresponding gene targets of Citron and Bergamot.Obtain depression gene targets using OMIM,TTD,and Cenecards data platforms.Using Venny 2.1 online software,draw Venn diagrams of the intersection of active ingredients and gene targets.Draw network diagrams between drugs,active ingredients,targets,and diseases using Cytoscape 3.7.2 software.Construct a protein-protein interaction(PPI)network diagram using the STRING data platform for intersecting genes.Using the Metascape data platform,perform gene ontology(GO)function and Kyoto Encyclopedia of Genesand and Genomes(KEGG)pathway enrichment analysis.A rat depression model was established using chronic unpredictable mild stress(CUMS)combined with solitary care,and animal experiments were conducted to verify the BDNF/TrkB/CREB signaling pathway obtained from network pharmacology research.Results The research results of network pharmacology methods show that there are 57 antidepressant active ingredients in Citron,65 antidepressant active ingredients in Bergamot,and important active ingredients include Acetic acid,3,4,7-trimethoxycoumarin and Citric acid,etc.Through the data platform,2717 depression targets and 430 intersection targets were identified.Through PPI network analysis,key gene targets for antidepressant effects in Citron and Bergamot were identified,including TP53,Protein kinase B1,CREB-binding protein,Brain derived neurotrophic factor,etc.Through KEGG analysis,it was found that important signaling pathways include pathways in cancer,PI3K-Akt signaling pathway,Neurotrophin signaling pathway,etc.By observing the neurotrophic factor BDNF/TrkB/CREB signaling pathway in depressed rats,the results showed that the medium dose groups of Citron and Bergamot could significantly increase serum BDNF content(P<0.05),and each treatment group could improve the damage of hippocampal neurons in rats.The high and medium dose groups of Citron and Bergamot significantly increased the expression of BDNF protein in the hippocampal CA1 region(P<0.05,P<0.01).Except for the low-dose group,which showed no difference in TrkB mRNA gene expression,all other treatment groups significantly increased the mRNA gene expression levels of hippocampal BDNF,TrkB and CREB(P<0.01).The medium dose group of Citron and Bergamot increased the expression of BDNF protein in the hippocampus(P<0.01),while the medium and low dose groups significantly increased the relative expression of TrkB protein in the hippocampus(P<0.05).The medium dose group showed an increasing trend in the relative expression of CREB protein.Conclusion Traditional Chinese medicine Citron and Bergamot have therapeutic effects on depression models in rats,and the mechanism of action may be related to the BDNF/TrkB/CREB signaling pathway.

Objective To explore the relationship between serum phospholipase A2(PLA2),S100 calcium-binding protein B(S100B) and carotid plaque in elderly patients with acute progressive cerebral infarction. Methods From January 2021 to June 2022,120 elderly patients with acute progressive cerebral infarction were enrolled in the study group,while 115 patients with non-progressive cerebral infarction were classified as non-progressive group and 100 healthy people as healthy group. The study group was divided into three groups:no plaque group (34 cases),stable plaque group (45 cases) and unstable plaque group (41 cases). To analyze the relationship between serum PLA2 and S100B levels and carotid plaque. ROC analysis of their predictive value for carotid plaque. Follow-up for 1 year,the survival rate was analyzed with recurrence and death as the end points. Results The levels of serum PLA2 and S100B in stable and unstable plaque groups were higher than those in non-plaque group,and the difference was statistically significant (P<0.05). Serum PLA2 and S100B were positively correlated with carotid plaque. ROC showed that the value of joint prediction was higher (P<0.05). Conclusion The levels of serum PLA2 and S100B are increased in elderly patients with acute progressive cerebral infarction,which is closely related to carotid plaque.

As one of the core theories of spleen governing transportation and transformation in the traditional Chinese medicine visceral manifestation theory,the modern biological basis of"spleen qi disperses essence"has not been fully elucidated.Lipids are one of the three major nutrients in the body,which are derived from exogenous absorption or endogenous transformation,and belong to the category of"grease"and"essence"substances in traditional Chinese medicine.Because of their hydrophobic nature,lipids require apolipoproteins to be transported in the bloodstream and used by the body;similarly,essence also needs spleen qi transformation to be distributed throughout the body and exert their nourishing effects,revealing a certain degree of inherent unity between the two.When the spleen qi functions properly,essence dispersal is orderly and lipid metabolism remains in homeostatic balance;if spleen deficient leads to impaired transportation,the essence will not be distributed,and the lipid turbidity will accumulate,causing disease.Classic strengthening spleen prescriptions such as Zexie Decoction,can reshape lipid homeostasis by regulating apolipoproteins.Based on apolipoprotein-mediated lipid metabolism,this paper explores the modern molecular biology basis of the theory of"spleen qi disperses essence,"which provides novel insights for enriching the modern research of traditional Chinese medicine visceral manifestation theory,and lays the foundation for clinical practice and theoretical innovation in the treatment of metabolic diseases from the spleen.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.