ObjectiveTo investigate the effects of salidroside （SAL） on the impaired bioactivity of endothelial progenitor cells （EPCs） in atherosclerotic （As） mice and the potential mechanisms regarding AMP-activated protein kinase （AMPK）. MethodsAtherosclerosis was induced in 8-week-old male ApoE^-/- mice with high-fat diet. Intragastric administration of SAL was given to one mice group to investigate the effects of SAL on aortic plaque burden， plasma NO level， the migration and angiogenic capabilities of bone marrow-derived EPCs （BM-EPCs）. The proliferation， migration and vasculogenic properties of EPCs isolated from As mice were investigated in vitro. AMPK-sh-RNA or the AMPK inhibitor Compound C was used to investigate the role of AMPK/Akt/eNOS pathway in the regulatory effects of SAL. ResultsCompared with As group， NO level was significantly elevated in SAL group. The sizes of atherosclerotic plaques at the aortic root were reduced with smaller lipid cores in SAL group compared with As group. Moreover， the migration and angiogenesis capacity of EPCs markedly decreased in As mice， while SAL treatment reversed these impairments. Incubation with SAL at concentrations of 20， 40， and 80 μmol/L for 48 hours significantly promoted the proliferation， migration， and angiogenesis of EPCs. AMPK-sh-RNA transfection abrogated the 20 μmol/L SAL improvement in EPC biological activities. Western blot analysis further demonstrated that treatment with Compound C blocked the activation of AMPK/Akt/eNOS signaling pathway induced by SAL. ConclusionSAL upregulates the biological functions of EPCs through activating the AMPK/Akt/eNOS signaling pathway， thereby ameliorating EPC dysfunction during the pathological progression of atherosclerosis.

[摘 要] 目的：探讨RNA结合基序蛋白15（RBM15）是否通过含跨膜Bax抑制基序蛋白6（TMBIM6）/TGF-β/Smad轴促进宫颈癌细胞增殖、迁移及侵袭。方法：收集2023年1月至2025年1月在苏州大学附属张家港医院接受手术治疗的82例宫颈癌患者的肿瘤组织与癌旁组织。应用R语言分析癌症基因组图谱（TCGA）数据库中RBM15、TMBIM6 mRNA的表达；采用免疫组织化学法和Western blotting法检测RBM15、TMBIM6蛋白表达；采用Kaplan-Meier曲线分析RBM15、TMBIM6 mRNA表达与宫颈癌患者预后的关系；采用CCK-8法、划痕实验及Transwell侵袭实验检测RBM15、TMBIM6对宫颈癌细胞增殖、迁移及侵袭的影响；利用基于序列的RNA腺苷甲基化位点预测工具（SRAMP）预测TMBIM6 mRNA的N6-甲基腺苷（m6A）修饰位点；采用RNA免疫共沉淀（RIP）实验、RNA衰变和挽救实验鉴定RBM15与TMBIM6 mRNA的相互作用；采用甲基化RNA免疫共沉淀定量PCR（MeRIP-qPCR）检测TMBIM6 mRNA的m6A富集；采用Western blotting法检测RBM15通过TMBIM6对宫颈癌细胞TGF-β/Smad通路相关蛋白表达的影响。结果：宫颈癌组织中RBM15 mRNA、TMBIM6 mRNA表达均高于癌旁组织（均P < 0.05），癌组织RBM15、TMBIM6阳性率均高于癌旁组织（均P < 0.001）。宫颈癌细胞系HeLa、MS-751、SiHa中RBM15、TMBIM6蛋白表达均高于正常宫颈上皮细胞系Ect1/E6E7（均P < 0.05）。国际妇产科联盟（FIGO）分期ⅠB2～ⅡB期宫颈癌组织中RBM15、TMBIM6蛋白阳性率高于ⅠA～ⅠB1期（P均 < 0.05）。RBM15 mRNA高表达组、TMBIM6 mRNA高表达组5年无进展生存率分别低于各自的低表达组（均P < 0.05）。宫颈癌组织中RBM15 mRNA与TMBIM6 mRNA表达呈正相关（P < 0.05）。SRAMP预测结果显示，TMBIM6 mRNA序列的960、24876、25203位点为高可信度m6A修饰位点。在HeLa、SiHa细胞中过表达RBM15后，TMBIM6 mRNA和蛋白表达升高（P < 0.05）；敲低RBM15后，TMBIM6 mRNA和蛋白表达降低（P < 0.05）。与IgG组相比，RBM15抗体免疫沉淀物中TMBIM6 mRNA显著富集。MeRIP-qPCR结果显示，TMBIM6 mRNA的960、24876、25203位点均存在明显的m6A富集。敲低RBM15可缩短TMBIM6 mRNA半衰期并降低其稳定性。敲低RBM15可抑制宫颈癌细胞增殖、迁移及侵袭，过表达TMBIM6可逆转上述影响。在HeLa、SiHa细胞中过表达TMBIM6后，TGF-β1、Smad2、Smad3蛋白表达升高；敲低RBM15后，上述蛋白表达降低，过表达TMBIM6可逆转该影响。结论：RBM15可能通过m6A修饰提高TMBIM6 mRNA稳定性并激活TGF-β/Smad通路，从而促进宫颈癌细胞增殖、迁移及侵袭。

Cilia,as cellular sensory organelles,actively partici-pate in and regulate cellular processes such as autophagy and metabolic breakdown during their generation and transportation.Autophagy,on the other hand,is a cell self-protection mecha-nism that maintains cellular homeostasis by clearing aggregates and damaged organelles.Combining recent research findings,this review comprehensively elucidates the bidirectional crosstalk between primary cilia and autophagy.Specifically,it highlights the crucial role of cilia-dependent signaling pathways in activa-ting cellular autophagy and how autophagy regulates cilia genera-tion and length by degrading specific ciliary proteins.Moreover,the dysregulation of primary cilia and autophagy is closely asso-ciated with the clinical manifestations and pathogenesis of vari-ous ciliopathy-related diseases such as polycystic kidney disease and tuberous sclerosis.In terms of pharmacotherapy,this review provides a comprehensive and in-depth overview of small mole-cule inhibitors targeting ciliogenesis,including cytoskeletal drugs and Hedgehog signaling pathway inhibitors.Despite the current limitations in clinical use,these drugs lay the groundw-ork for developing highly specific targeted small molecule inhibi-tors of ciliogenesis and for the treatment of ciliopathies and canc-ers.By systematically discussing ciliogenesis,autophagy,disea-ses and drugs,this review offers new insights for further elucida-ting the crosstalk between ciliogenesis and autophagy,exploring their pathological mechanisms in disease development,and de-veloping therapeutic strategies in the future.

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 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.

Post-stroke spasticity is a series of symptoms after stroke,such as hand and foot urgency,unflexion and extension of muscles,etc.In order to deeply understand the cognition of post-stroke spasticity of ancient Chinese physicians and comb out their therapeutic thoughts,this study took the General Catalogue of Chinese Ancient Books of Traditional Chinese Medicine as a bibliographic reference,all the ancient Chinese literature on spasms after stroke was retrieved manually and by computer,and then sorted and analyzed,and classified them by longitudinal time,and extracted the description about post-stroke spasticity,including medical classics,prescriptions,clinical evidence,medical records and so on.And this paper verified and summarized the etiology,pathogenesis,functional and indications and prescription characteristics of spasticity after stroke,in order to deeply understand systematic theories and treatment ideas of the ancient medical practitioners in the bud,development and mature stages of their understanding of spasticity after stroke,and provide the theoretical basis for the later doctors to understand this disease and the modern clinical treatment of traditional Chinese medicine.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective:This study aimed to investigate the effects of glucagon-like peptide-1 receptor agonists(GLP-1RAs) on the emotional behaviors in wild-type mice and explore the underlying mechanisms.Methods:The study consisted of two parts.(1) Drug effect evaluation: C57BL/6 mice were randomly assigned to saline, semaglutide, or liraglutide groups. After 4 weeks of continuous subcutaneous administration, anxiety-like behaviors were evaluated by the open field tests and elevated plus maze, and depression-like behaviors were assessed by the forced swimming test and tail suspension test. Neurotransmitter levels, including NE, DA, 5-HT, GABA, and glutamate, were measured in target brain regions using LC-MS/MS. Hypothalamic activation subregions were identified by c-fos immunohistochemistry.(2) Time-course analysis: Mice received short-term administration(2 weeks), long-term administration(4 weeks), or drug withdrawal(assessed 4 weeks post-withdrawal). Behavioral performance, hypothalamic neurotransmitter levels, and plasma adrenocorticotropic hormone and corticosterone were measured.Results:Compared with the saline group, both GLP-1RAs significantly prolonged immobility time in the forced swimming and tail suspension tests. Multiple brain regions exhibited neurotransmitter abnormalities, including marked reductions in hypothalamic norepinephrine, dopamine, and γ-aminobutyric acid levels. Both GLP-1RAs significantly increased c-fos positive cell counts in the suprachiasmatic nucleus and arcuate nucleus of the hypothalamus. Time-course analysis revealed that short-term administration did not induce depressive phenotypes, whereas long-term administration led to depression-like behaviors, which recovered after drug withdrawal. Plasma adrenocorticotropic hormone and corticosterone levels were elevated even after short-term treatment and remained high after drug withdrawal, while hypothalamic neurotransmitter abnormalities normalized upon withdrawal.Conclusion:GLP-1RAs induce depression-like behaviors in a time-dependent manner, with neurotransmitter imbalance and persistent hyperactivation of the HPA axis likely contributing to the pathophysiological mechanism.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.