OBJECTIVE To screen a single matrix， prepare dissolving microneedles of Pterocarya hupehensis total flavonoids（PHTF-MN）， and characterize it while evaluating its analgesic effects.METHODS Using microneedle morphology and puncture rate as evaluation indicators， the matrix was screened from polyvinyl alcohol （PVA）， polyvinylpyrrolidone K30 （PVP K30）， PVP K90， and sodium hyaluronate with relative molecular weights of 15 000 and 60 000 （HA 1.5w and HA 6w ）. PHTF-MN was prepared by the layer-by-layer casting method with the selected matrix， and the appearance and morphology， total flavonoid content， mechanical properties， puncture performance， dissolution properties， and drug release behavior of the obtained PHTF-MN were characterized. Using male BALB/c mice as test subjects and aspirin （ASA） as a positive control， the analgesic effects of the microneedles were evaluated using a formalin-induced pain model.RESULTS Blank microneedles prepared with 30% HA 1.5w exhibited optimal surface flatness and the membrane puncture rate （through 4 layers of parafilm membrane） reaching 78%. The PHTF-MNs （with PHTF contents of 10， 20， 30， 40， and 50 mg/g in the matrix） exhibited uniform arrays and intact tips， with RSDs for total flavonoid contents all below 7% （ n ＝8）. The single-needle puncture forces were 1.46 and 1.07 N （with PHTF contents of 30 and 50 mg/g in the matrix， respectively）. The skin penetration rate approached 100%， with visible puncture marks in the stratum corneum and drug residue （with a PHTF content of 50 mg/g in the matrix）. After 30 min of fixation， the needles had almost completely dissolved， and the skin retention rates all exceeded 90% （with PHTF contents of 10， 30， and 50 mg/g in the matrix， respectively）. The cumulative release within 8 h was （134.64±2.03） μg/cm 2 ， and the fit to the first-order kinetic equation （ R 2 ＝0.950 1） was highest （with a PHTF content of 50 mg/g in the matrix）. Low- and high-dose PHTF-MN （containing 85.26 and 145.03 μg of total flavonoids per patch， respectively； 1 patch/day） significantly shortened the cumulative time of phase Ⅱ pain response in mice （ P ＜0.05）， with pain inhibition rates （43.67% and 59.78%） comparable to those of ASA （53.70%）.CONCLUSIONS PHTF-MN using HA 1.5w as a single matrix was successfully prepared. This formulation features a simplified preparation process， uniform drug loading， favorable mechanical properties， resistance to fracture， and rapid dissolution. Its drug release behavior conforms to a first-order kinetic model， and its analgesic effect is comparable to that of ASA.

Objectives:To preliminarily investigate the safety and efficacy of same-day discharge(SDD)following radiofrequency catheter ablation for arrhythmia.Methods:A total of 50 consecutive patients who underwent radiofrequency catheter ablation for arrhythmia in the SDD strategy at Fuwai Hospital from 8 July 2024 to 18 September 2024 were included in this analysis.The study evaluated the immediate success rate of the ablation,the rate of all-cause and arrhythmia-related readmission,outpatient or emergency visits and incidence of complications within 30 days post ablation,and recurrence rate of arrhythmias over a 3-month follow-up period.Results:The average age of the 50 patients was(47.2±16.1)years old,32 patients(64.0%)were male.Radiofrequency catheter ablation was performed in 47 patients(94.0%),including 18(36.0%)atrial fibrillation(AF)ablation.Three patients(6.0%)underwent electrophysiological study only.The immediate success rate for ablation patients was 100%(47/47).None of the patients developed vascular puncture-related or ablation-related complications.The average hospital stay and postoperative observation time were(6.84±1.13)hours and(3.40±1.12)hours,respectively.The all-cause and arrhythmia-related readmission,outpatient or emergency visits rates within 30 days were 12.0%(6/50)and 2.0%(1/50),respectively.Two patients(4.0%)post ablation experienced AF recurrence during the 3-months follow-up period.Conclusions:Radiofrequency catheter ablation for arrhythmias in SDD strategy is safe,effective,and feasible.

Objective To examine the time window effect of high-load exerciseon skeletal muscle in-flammation genes,and identify the key genes and signaling pathways involved in this process.Methods Forty-eight Sprague-Dawley rats were randomly assigned to a control group(group C,n=8)and an ex-ercise group(group E,n=40).Gastrocnemius muscles were collected immediately(group E0),12h(group E12),24h(group E24),48h(group E48),and 72 h(group E72)after exercise for transcrip-tome sequencing.Differentially expressed genes(DEGs)were identified,and enrichment analysis was carried out using the Gene Ontology(GO)and the Kyoto Encyclopedia of Genes and Genomes(KEGG)annotations.Meanwhile,inflammation-related genes were obtained from databases,and differ-entially expressed inflammation-related genes(DEIRGs)were done through identifying their intersec-tion with DEGs.Moreover,the Mfuzz algorithm was used for time series clustering to obtain subsets with similar characteristics.GO and KEGG analyses,along with protein interaction network analysis,were performed to obtain key DEIRGs,followed by secondary functional enrichment to analyze changes in expression of key genes over time and identify key signaling pathways.Results Seven DEIRG clus-ters were obtained through Mfuzz time series clustering of skeletal muscle inflammation genes after high-load exercise.Overall,the expression of DEGs in cluster 5 was downregulated,while that in cluster 7 was upregulated.The expression of DEGs in clusters 3 and 4 was upregulated at E0 and rap-idly downregulated at E12.In contrast,the expression of DEGs in cluster 2 and 6 were downregulated at E0 and rapidly upregulated at E12.The expression of DEGs in cluster 1 was upregulated at E0,rapidly downregulated at E12,and remained upregulated at E24.Screening identified TP53,STAT3,CD44,AKT1,KDR,GJA1,CYCS,HIF1A,IQGAP3,FASN,and TFRC as key DEIRGswhich were enriched in apoptosis,HIF-1,apoptosis,ferroptosis,MAPK,VEGF,PI3K-Akt,insulin resistance,FoxO,AMPK and the JAK-STAT signaling pathway.Conclusion Inflammation-related genes exhibit temporal dynamic changes in exercise-induced muscle damage and show significant time window effects at 12 h after exercise.The key targets STAT3,AKT1 and HIF-1A react to exercise-induced muscle damage through the JAK-STAT,PI3K-Akt,HIF-1 and VEGF signaling pathways,and promote tissue repair.

Aim To investigate the mechanism of ac-tion of Qingre Zhixue granules in the treatment of IgA vasculitic nephritis(IgAVN)based on network phar-macology and animal experiments.Methods The ac-tive ingredients and targets of Qingre Zhixue granules were screened out by TCMSP database.The disease targets of IgAVN were retrieved by Disgenet,Gene-cards OMIM and TTD databases.The intersection tar-gets were obtained by WeChat online database,and the information was imported into Cytoscope 3.7.1 soft-ware and STRING analysis platform to construct a drug-active component-therapeutic target network.Based on the core targets,GO and KEGG pathway enrichment a-nalysis was performed through the Metascape database to select key targets and core active components.The results of network pharmacology were verified by ani-mal experiments.The animal model of IgAVN was con-structed by the combination of disease and syndrome.The urine red blood cells and 24-hour urine protein of IgAVN model rats after intervention of Qingre Zhixue granules were detected.HE staining and IgA immuno-fluorescence deposition of renal tissue were observed.Western blot and qRT-PCR were used to detect the ex-pression of core targets in renal tissue.Results Net-work pharmacology showed that 109 active ingredients,402 drug targets,1 285 disease targets and 113 inter-section targets were obtained.The core targets screened by protein interaction and network topology a-nalysis were IL6,TNF,VEGFA,etc.The core drug ingredients were quercetin,paeoniflorin,luteolin,kaempferol and baicalein.A total of 2 545 gene func-tions were enriched by GO,and 164 gene pathways were enriched by KEGG.Qingre Zhixue granules could treat IgAVN by regulating TNF signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,HIF-1 signaling pathway,Toll receptor signaling path-way,NF-κB signaling pathway and apoptosis.Animal experiments showed that compared with the blank group,the urine red blood cells and 24-hour urine pro-tein quantification in the model group increased(P＜0.05);the expression of serum IL-6,TNF-α and VEGF-α increased(P＜0.05).HE staining showed glomerular mesangial proliferation,capillary lumen ste-nosis,accompanied by a small amount of inflammatory cell infiltration,glomerular IgA immunofluorescence deposition;the expression of TNF-α,p-p65,p-p38 protein and TNF-α mRNA in renal tissue increased(P＜0.05).After the intervention of Qingre Zhixue gran-ules,urine red blood cells and 24-hour urine protein decreased(P＜0.05).The changes of renal HE stai-ning were improved and glomerular IgA deposition was reduced.TNF-α,p-p65,p-p38 protein and TNF-αmRNA in renal tissue decreased(P＜0.05).Conclu-sions The active ingredients such as quercetin,peony glycoside and luteolin Qingre Zhixue granules regulate TNF signaling pathway,MAPK signaling pathway,IL-17 signaling pathway and reduce IL-6,TNF-α and VEGF-α in the treatment of IgAVN.

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.

Objective:To establish an in vitro cell model simulating acute graft-versus-host disease(aGVHD)bone marrow microenvironment injury with the advantage of mouse serum of aGVHD model and explore the effect of serum of aGVHD mouse on the adipogenic differentiation ability of mesenchymal stem cells(MSCs).Methods:The 6-8-week-old C57BL/6N female mice and BALB/c female mice were used as the donor and recipient mice of the aGVHD model,respectively.Bone marrow transplantation(BMT)mouse model(n=20)was established by being injected with bone marrow cells(1 × 10'per mouse)from donor mice within 4-6 hours after receiving a lethal dose(8.0 Gy,72.76 cGy/min)of y ray general irradiation.A mouse model of aGVHD(n=20)was established by infusing a total of 0.4 ml of a mixture of donor mouse-derived bone marrow cells(1 × 107 per mouse)and spleen lymphocytes(2 × 106 per mouse).The blood was removed from the eyeballs and the mouse serum was aspirated on the 7th day after modeling.Bone marrow-derived MSCs were isolated from 1-week-old C57BL/6N male mice and incubated with 2％,5％and 10％BMT mouse serum and aGVHD mouse serum in the medium,respectively.The effect of serum in the two groups on the in vitro adipogenic differentiation ability of mouse MSCs was detected by Oil Red O staining.The expression levels of related proteins PPARy and CEBPα were detected by Western blot.The expression differences of key adipogenic transcription factors including PPARy,CEBPα,FABP4 and LPL were determined by real-time quantitative PCR(RT-qPCR).Results:An in vitro cell model simulating the damage of bone marrow microenvironment in mice with aGVHD was successfully established.Oil Red O staining showed that the number of orange-red fatty droplets was significantly reduced and the adipogenic differentiation ability of MSC was impaired at aGVHD serum concentration of 10％compared with BMT serum.Western blot experiments showed that adipogenesis-related proteins PPARy and CEBPα expressed in MSCs were down-regulated.Further RT-qPCR assay showed that the production of PPARy,CEBPα,FABP4 and LPL,the key transcription factors for adipogenic differentiation of MSC,were significantly reduced.Conclusion:The adipogenic differentiation capacity of MSCs is inhibited by aGVHD mouse serum.

AIM:To investigate the mechanism through which aerobic exercise improves inflammatory senes-cence in SAMP8 mice via Janus kinase 3(JAK3)-signal transducer and activator of transcription 5α(STAT5α)signaling pathway and to provide novel insights for anti-inflammatory aging interventions.METHODS:Sixteen 28-week-old SAMP8 mice were randomly divided into model(Mod)group and exercise(Exe)group,with 8 mice in each group.Addi-tionally,8 senile SAMR1 mice served as control(Con)group.The mice in Exe group underwent an 8-week aerobic training regimen on a treadmill.We monitored the changes in hair quality and body weight,immune organ indexes,histomorpho-logical alterations in immune organs,the expression levels of spleen aging marker P16,and the serum and spleen levels of inflammatory factors[tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)]and aging indicator IL-2.Moreover,we examined the alterations in the mRNA and protein expression of IL-2,JAK3 and STAT5α in the spleen.RESULTS:(1)Compared with Con group,the mice in Mod group exhibited decreased hair luster and volume,with some instances of alopecia areata,increased body weight,markedly reduced spleen and thymus indexes,evident atrophy and senescence of immune organs,and markedly decreased concentration of IL-2 in the serum and spleen.The expression of P16 in the spleen,and the serum and spleen levels of inflammatory factors TNF-α and IL-1β were significantly increased.The mRNA expression of IL-2 and IL-2 receptor subunit gamma(IL-2RG)in the spleen was markedly decreased,whereas that of JAK3 and STAT5α was markedly increased.Furthermore,the protein expression of IL-2 in the spleen was markedly de-creased,whereas that of STAT5α and JAK3 was markedly increased.(2)Compared with Mod group,the mice in Exe group showed relatively vigorous hair growth and better hair luster,lower body weight,markedly increased spleen and thy-mus indexes,and delayed immune organ aging.The concentration of IL-2 in the serum and spleen was markedly in-creased,while the expression of P16 in the spleen was markedly decreased.The levels of TNF-α and IL-1β in the serum and spleen were markedly decreased.The mRNA expression of IL-2 and IL-2RG in the spleen was markedly increased,whereas that of JAK3 and STAT5α was markedly decreased.The protein levels of IL-2 were markedly increased,whereas those of STAT5α and JAK3 were markedly decreased.CONCLUSION:Aerobic exercise can delay inflammatory aging in mice possibly through the JAK3-STAT5α signaling pathway.

Adenoid cystic carcinoma(ACC)of the cervix is a rare and highly aggressive subtype of cervical cancer,accounting for less than 1%of all cervical cancer cases.ACC predominantly affects postmenopausal women over the age of 60,with postmenopausal vaginal bleeding being the most common symptom.Diagnosis of ACC primarily relies on histopathological examination and immunohistochemical analysis.Although there is currently no standard treatment protocol,surgical resection combined with radiotherapy or concurrent chemoradiotherapy is considered to be an effective approach.However,the effectiveness is limited,particularly in advanced cases,which generally have a poor prognosis.The treatment and prognosis of ACC are closely related to tumor staging,perineural invasion,and margin status.This paper discusses the clinical data and follow-up of six ACC patients treated at our institution,and goes through a literature review,examines its clinical features and treatment outcomes,underscores the critical importance of early diagnosis and individualized treatment.