Background and aims Hepatocellular carcinoma (HCC) cells are metabolically reprogrammed for excessive uptake and metabolism of many nutrients. The tumor suppressive microRNA-148a-3p (miR-148a-3p) is downregulated in HCC, whereas its function in regulating HCC cell metabolism remains obscure. Herein we aimed to delineate the role of miR-148a-3p in HCC cell metabolism by using novel bioengineered miR-148a-3p (BioRNALeu/miR-148a-3p) agent produced in vivo. Methods BioRNALeu/miR-148a-3p was designed by using human leucyl transfer RNA fused hsa-pre-miR-34a carrier, overexpressed in Escherichia coli (E. coli), and purified to high homogeneity. After transfection into HCC cells, the released miR-148a-3p levels were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was determined by CellTiter-Glo assays. Targets were validated by dual-luciferase reporter assays, immunoblotting, and immunofluorescence confocal imaging. Glycolysis capacity was evaluated by Seahorse XF assays, and glucose, lactate, and amino acid levels were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Results BioRNALeu/miR-148a-3p was efficiently processed into target miR-148a-3p in HCC cells to effectively inhibit cell proliferation in a dose- and time-dependent manner. Mechanistically, miR-148a-3p suppressed the protein levels of glucose transporter GLUT1/SLC2A1 and L-type amino acid transporter LAT1/SLC7A5 via acting on their 3′-untranslated regions, as well as amino acid transporter ASCT2/SLC1A5. These, in turn, led to a reduction of glucose uptake, lactate production, and glycolytic flux in HCC cells, and alteration of intracellular amino acid metabolome including glutamine, leucine, phenylalanine, tyrosine, and methionine. Conclusions Reintroduction of miR-148a-3p into HCC cells modulates glucose and amino acid metabolism via regulating multiple SLC transporters, thereby suppressing HCC cell viability. These findings highlight the role of miR-148a-3p in HCC cell metabolism and potential of bioengineered miRNA molecules for functional studies and therapeutic development.

Objective:To investigate the impact of lesions in different nuclei of the subcortical basal ganglia on speech processing functions in patients with post-stroke dysarthria.Methods:From July 2022 to September 2023, a total of 20 patients with post-stroke dysarthria (patient group) and 22 healthy individuals (control group) were recruited. Brain imaging data, including structural magnetic resonance imaging(MRI) and diffusion-weighted imaging (DWI), as well as behavioral data of speech fluency task and picture association task were collected. Structural MRI data was analyzed using SPM12 software to perform voxel-based morphometry (VBM), measuring cortical thickness and gray matter volume (VGM) in specific nuclei of the basal ganglia. Behavioral metrics, such as reaction time (RT) and the number of valid responses were extracted for each task. Statistical analysis was conducted using SPSS 27.0 and R 4.0 softwares. Spearman correlation analysis was applied to examine relationships between neuroimaging parameters and behavioral performance indicators.Results:The patient group exhibited significantly smaller gray matter volumes in both left and right caudate nuclei((2.69±0.92)mm 3, (3.17±0.91)mm 3 ) and putamen (3.31±1.08)mm 3, (3.66±0.91)mm 3) compared to the control group (caudate nuclei (3.19±0.36)mm 3, (3.49±0.52)mm 3 putamen (4.52±0.54)mm 3, (4.72±0.64)mm 3), with statistically significant differences ( t=-2.83, 1.68; t=-3.59, 3.52, both P<0.05). Behavioral experiments revealed that the patient group exhibited significantly prolonged reaction time during picture association and naming tasks (1 910.50(1 214.25, 3 806.75) ms, 1 362.00(978.00, 2 297.00) ms) compared to the control group (1 618.00(1 162.75, 2 401.75) ms, 1 224.00(984.25, 1 661.50) ms; Z=-5.20, -4.61, both P<0.05). Gray matter volumes in the left caudate nucleus and left putamen exhibited negative correlations with reaction times during the picture naming task ( r=-0.52, -0.54, both P<0.05). Additionally, the gray matter volume of the left putamen demonstrated a positive correlation with the number of valid responses in speech fluency task-T2 ( r=0.46, P<0.05), whereas the left globus pallidus volume showed a negative correlation with speech fluency task-T1 ( r=-0.51, P<0.05) with the same measure. Conclusion:Lesions in the left subnuclei of the basal ganglia directly impair early-stage speech functions, including conceptual preparation and lexical selection, whereas right-side lesions exert less pronounced effects on linguistic performance compared to their left counterparts. Furthermore, the basal ganglia's involvement in higher-order linguistic processing may represent an indirect consequence of cognitive decline.

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.

Rheumatoid arthritis(RA)is a chronic autoimmune disease of unknown etiology that can cause joint destruction and deformity.As a small molecule cytokine,the chemokine C-X-C motif chemokine ligand 12(CXCL12)regulates the pathogenesis of rheumatoid arthritis by binding to the specific receptor CXC chemokine receptor 4(CXCR4).Therefore,based on the bio-logical characteristics of CXCL12 and CXCR4,this paper intro-duces the pathogenesis of CXCL12/CXCR4 in RA and summari-zes the progress in RA-related research,with the aim of providing clinical value for understanding the pathogenesis of RA and de-veloping novel therapeutic targets.

Objective To observe the mid-and long-term effects of Kegel training combined with Pilates training on urinary conti-nence recovery in different body mass index(BMI)male patients with urinary incontinence after prostatectomy.Methods From May,2023 to June,2024,48 patients in Beijing Bo'ai Hospital were recruited and divided into group A(<25 kg/m2,n=15),group B(25 to 30 kg/m2,n=18)and group C(>30 kg/m2,n=15)according to their BMI.All the groups performed Kegel training combined with Pilates training for two months,and followed up at six months from baseline.They were evaluated with one hour pad test,the number of daily urinary incontinence,In-ternational Consultation on Incontinence Questionnaire-Short Form(ICIQ-SF)and modified Oxford Rating Scale before treatment,and four weeks,eight weeks and six months after treatment.Results The intra-group effect,the inter-group effect and interaction effect were significant in the results of one hour pad test and the daily number of urinary incontinence(F>2.955,P<0.05).Post Hoc test showed that they were worse in group C than in groups A and B(P<0.05),and the number of daily urinary incontinence was more in group B than in group A(P<0.05).There was significant difference in the scores of ICIQ-SF and modified Ox-ford Rating Scale among groups in different time points after treatment(Z>10.476,P<0.05)except the score of ICIQ-SF four weeks after treatment(P>0.05),and they were the worst in group C.BMI(group A=1,group B=2,group C=3)was correlated with the results of one hour pad test(r=0.79,P<0.001),the number of daily uri-nary incontinence(r=0.68,P<0.001),and the scores of ICIQ-SF(r=0.68,P<0.001)and modified Oxford Rating Scale(r=-0.47,P=0.001)six months after treatment.Conclusion Kegel training combined with Pilates training could improve the urinary control in patients with urinary in-continence after prostatectomy.The decrease of BMI can promote the recovery of urinary control,and improve the symptoms of later urinary incontinence in mid-and long-term.

Objective:To investigate the impact of lesions in different nuclei of the subcortical basal ganglia on speech processing functions in patients with post-stroke dysarthria.Methods:From July 2022 to September 2023, a total of 20 patients with post-stroke dysarthria (patient group) and 22 healthy individuals (control group) were recruited. Brain imaging data, including structural magnetic resonance imaging(MRI) and diffusion-weighted imaging (DWI), as well as behavioral data of speech fluency task and picture association task were collected. Structural MRI data was analyzed using SPM12 software to perform voxel-based morphometry (VBM), measuring cortical thickness and gray matter volume (VGM) in specific nuclei of the basal ganglia. Behavioral metrics, such as reaction time (RT) and the number of valid responses were extracted for each task. Statistical analysis was conducted using SPSS 27.0 and R 4.0 softwares. Spearman correlation analysis was applied to examine relationships between neuroimaging parameters and behavioral performance indicators.Results:The patient group exhibited significantly smaller gray matter volumes in both left and right caudate nuclei((2.69±0.92)mm 3, (3.17±0.91)mm 3 ) and putamen (3.31±1.08)mm 3, (3.66±0.91)mm 3) compared to the control group (caudate nuclei (3.19±0.36)mm 3, (3.49±0.52)mm 3 putamen (4.52±0.54)mm 3, (4.72±0.64)mm 3), with statistically significant differences ( t=-2.83, 1.68; t=-3.59, 3.52, both P<0.05). Behavioral experiments revealed that the patient group exhibited significantly prolonged reaction time during picture association and naming tasks (1 910.50(1 214.25, 3 806.75) ms, 1 362.00(978.00, 2 297.00) ms) compared to the control group (1 618.00(1 162.75, 2 401.75) ms, 1 224.00(984.25, 1 661.50) ms; Z=-5.20, -4.61, both P<0.05). Gray matter volumes in the left caudate nucleus and left putamen exhibited negative correlations with reaction times during the picture naming task ( r=-0.52, -0.54, both P<0.05). Additionally, the gray matter volume of the left putamen demonstrated a positive correlation with the number of valid responses in speech fluency task-T2 ( r=0.46, P<0.05), whereas the left globus pallidus volume showed a negative correlation with speech fluency task-T1 ( r=-0.51, P<0.05) with the same measure. Conclusion:Lesions in the left subnuclei of the basal ganglia directly impair early-stage speech functions, including conceptual preparation and lexical selection, whereas right-side lesions exert less pronounced effects on linguistic performance compared to their left counterparts. Furthermore, the basal ganglia's involvement in higher-order linguistic processing may represent an indirect consequence of cognitive decline.

Objective:To investigate the application effect of strengths,weaknesses,opportunities and threats(SWOT)analysis-guided risk control management in patients with atherosclerotic obliterans(ASO).Methods:This randomized controlled study enrolled 105 ASO patients admitted in Chinese People's Liberation Army Rocket Force Characteristic Medical Center between November 2017 and November 2022.They were divided into control group(n=52,routine nursing)and intervention group(n=53,SWOT analysis-guided risk control management).Renal function,postoperative recovery,psychological status,sleep quality,pain,incidence of adverse reactions and nursing satisfaction were compared between two groups.Results:3 d after surgery,compared with patients in con-trol group,those in intervention group had significant lower cystatin C(CysC)[(1.04±0.11)mg/L vs.(1.40±0.12)mg/L],serum creatinine(Scr)[(70.70±6.48)μmol/L vs.(82.93±9.32)μmol/L]and urinary protein[(2.38±0.13)g/L vs.(3.56±0.17)g/L](P＜0.001 all);7d after surgery,compared with patients in control group,those in intervention group had significant lower incidence of adverse reactions(7.55％vs.23.08％),scores of self-rating anxiety scale(SAS)[(34.09±3.40)points vs.(39.50±3.12)points],self-rating depression scale(SDS)[(24.42±3.34)points vs.(32.04±2.77)points],Pittsburgh sleep quality index(PSQI)[(7.09±1.48)points vs.(10.19±1.65)points]and visual analogue scale(VAS)[(3.09±0.84)points vs.(4.33±1.15)points],and significant higher limp distance[(2407.89±130.09)m vs.(1521.26±102.26)m]and ankle-brachi-al index[(0.87±0.03)vs.(0.62±0.04)](P＜0.05 or＜0.01).After discharge,nursing satisfaction in inter-vention group was significantly higher than that of control group(92.45％vs.73.08％,P=0.008).Conclusion:SWOT analysis-guided risk control management could effectively reduce the damage of renal function caused by in-terventional surgery,reduce pain,improve negative emotion and sleep quality,and reduce incidence of adverse e-vents after surgery in patients with arteriosclerosis obliterans.

Objective:To construct and evaluate the predictive performance of a multiphase ultrasound radiomics model for microvascular invasion（MVI）in hepatocellular carcinoma（HCC）.Methods:A total of 126 patients with pathologically confirmed HCC were retrospectively enrolled from 4 medical centers between May 2018 and July 2025，including the First Hospital of Shanxi Medical University，Shanxi Province Third People's Hospital，Changzhi People's Hospital，and the Organ Transplant Center of the Affiliated Hospital of Qingdao University. A total of 630 ultrasound images of the lesions in different phases were collected，from which 1 561 radiomic features were extracted. The patients from medical institutions in Shanxi Province were chosen as the training set（ n=91），and the patients from the Organ Transplant Center of the Affiliated Hospital of Qingdao University were chosen as the validation set（ n=35）. In the training set，37.4%（34/91）patients presented MVI（+），whereas in the validation set，54.3%（19/35）patients presented MVI（+）. Radiomics features were extracted from ultrasound images，and features related to the MVI（+）were selected through dimensionality reduction analysis. Five multiple machine learning algorithms were used to construct predictive models，which were then evaluated using an external validation set. The Radscore was calculated，and a nomogram was constructed combining Radscore with ultrasound and clinical characteristics to predict MVI. Results:The model combining radiomics features from the portal venous phase and the delay phase showed the best predictive performance in both the training and validation sets，with area under curve（AUC）values of 0.835 and 0.727，respectively. The prediction model developed using radiomics Radscore and clinical indicators could be represented and presented as a nomogram.Conclusions:The radiomics model based on multi-phase ultrasound offers a novel approach for non-invasive preoperative prediction of MVI in liver cancer. Furthermore，its integration with clinical features aids in optimizing clinical treatment strategies.