Objective To explore the mechanism of Lacticaseibacillus paracasei E6 for improving vinorelbine-induced immunosuppression in zebrafish.Methods The intestinal colonization of L.paracasei E6 labeled by fluorescein isothiocyanate(FITC)in zebrafish was observed under fluorescence microscope.In a zebrafish model of vinorelbine-induced immunosuppression,the immunomodulatory activity of L.paracasei E6 was assessed by analyzing macrophage and neutrophil counts in the caudal hematopoietic tissue(CHT),the number of T-lymphocyte,and the expressions of interleukin-12(IL-12)and interferon-γ(IFN-γ).The contents of short-chain fatty acids(SCFAs)in L.paracasei E6 fermentation supernatant and the metabolites of L.paracasei E6 in zebrafish were detected by LC-MS/MS-based targeted metabolomics.The immunomodulatory effects of the SCFAs including sodium acetate,sodium propionate and sodium butyrate were evaluated in the zebrafish model of immunosuppression.Results After inoculation,green fluorescence of FITC-labeled L.paracasei E6 was clearly observed in the intestinal ball,midgut and posterior gut regions of zebrafish.In the immunocompromised zebrafish model,L.paracasei E6 significantly alleviated the reduction of macrophage and neutrophil counts in the CHT,increased the fluorescence intensity of T-lymphocytes,and promoted the expressions of IL-12 and IFN-γ.Compared with MRS medium,L.paracasei E6 fermentation supernatant showed significantly higher levels of acetic acid,propionic acid and butyric acid,which were also detected in immunocompromised zebrafish following treatment with L.paracasei E6.Treatment of the zebrafish model with sodium acetate and sodium propionate significantly increased macrophage and neutrophil counts in the CHT and effectively inhibited vinorelbine-induced reduction of thymus T cells.Conclusion L.paracasei E6 can improve vinorelbine-induced immunosuppression in zebrafish through its SCFA metabolites acetic acid and propionic acid.

Objective To investigate the efficacy of Lactobacillus plantarum ZG03(L.plantarum ZG03)for ameliorating oxidative stress in zebrafish.Methods We evaluated the growth pattern of L.plantarum ZG03,observed its morphology using field emission scanning electron microscopy,and assessed its safety and potential efficacy with whole-genome sequencing for genetic analysis.FITC-labeled ZG03 was used to observe its intestinal colonization in zebrafish.In a zebrafish model of 2%glucose-induced oxidative stress,the effect of ZG03 was evaluated by assessing the changes in neutrophils in the caudal hematopoietic tissue(CHT),superoxide dismutase(SOD)activity,reactive oxygen species(ROS)levels,and malondialdehyde(MDA)content.Liquid chromatography-mass spectrometry-based targeted metabolomics was used for analyzing short-chain fatty acids(SCFAs)in the zebrafish,and the antioxidant effects of the key metabolites(acetate,propionate,and caproate)were tested.Results On MRS agar,L.plantarum ZG03 formed circular,smooth,moist,and milky-white colonies with a rod-shaped cell morphology.Genomic analysis revealed abundant sugar metabolism gene clusters.After inoculation of FITC-labeled L.plantarum ZG03 in zebrafish,green fluorescence was clearly observed in the intestinal bulb,mid-intestine,and hind intestine.In zebrafish with glucose-induced oxidative stress,L.plantarum ZG03 significantly reduced ROS levels and the number of neutrophils in the CHT with increased SOD activity.L.plantarum ZG03 significantly increased the content of SCFAs including acetic acid,propionic acid,and caproic acid in zebrafish metabolites.In addition,sodium acetate,sodium propionate,and sodium caproate in the SCFAs significantly increased SOD activity in the zebrafish models.Conclusion L.plantarum ZG03 ameliorates oxidative stress in a glucose-induced zebrafish model through its metabolites,particularly the SCFAs including acetic acid,propionic acid and caproic acid.

Objective:To investigate the diagnostic efficacy of time-dependent diffusion MRI (t d-dMRI)-derived microstructural parameters for clinically significant prostate cancer (csPCa) and their associations with the pathological grade of prostate cancer(PCa) based on the International Society of Urological Pathology (ISUP) grades. Methods:This cross-sectional study prospectively enrolled 196 patients suspected of PCa from March 2023 to March 2024 at the First Affiliated Hospital, Sun Yat-Sen University. All patients underwent multiparametric MRI and t d-dMRI to obtain microstructural parameters, including cell diameter (d), intracellular volume fraction (f in), extracellular diffusion coefficient (D ex), cellularity, and apparent diffusion coefficient (ADC) value at oscillation frequencies of 33 Hz, 17 Hz, 0 Hz (ADC 33, ADC 17, and ADC 0). Pathologically, 95 cases were classified as csPCa (ISUP 2-5), and the rest 101 cases were classified as non-csPCa (benign or ISUP 1). Comparison of these microstructural metrics was made between csPCa and non-csPCa groups by independent t-tests or Mann-Whitney U tests, and multivariable logistic regression was used to identify independent predictors. A combined diagnostic model was then constructed based on the independent predictors. The receiver operating characteristic curve analysis was used to evaluate the diagnostic performance. Finally, in PCa, the correlation between microstructural parameters and ISUP grades was investigated by Spearman correlation. Results:The t d-dMRI measurements, including d, f in, cellularity, ADC 33,ADC 17 and ADC 0, were significantly different between csPCa and non-csPCa groups (All P<0.05). But D ex was not significantly different between the two groups ( Z=-1.27, P=0.204). The area under the receiver operating characteristic curve (AUC) for diagnosing csPCa were 0.701 (95% CI 0.628-0.775) for d, 0.869 (95% CI 0.819-0.920) for f in, 0.884 (95% CI 0.835-0.932) for cellularity, 0.777 (95% CI 0.712-0.842) for ADC 33, 0.852 (95% CI 0.799-0.905) for ADC 17, and 0.840 (95% CI 0.786-0.894) for ADC 0. Cellularity ( OR=6.142, 95% CI 2.920-12.929, P<0.001) and ADC 17 ( OR=0.108, 95% CI 0.027-0.429, P=0.002) were identified as the independent predictors, and their combined model achieved an AUC of 0.896 (95% CI 0.852-0.941). In PCa f in and cellularity were positively correlated with ISUP grades ( r=0.490 and 0.397, P<0.001), while ADC 33, ADC 17, and ADC 0 were negatively correlated with ISUP grades ( r=-0.198, -0.345, -0.360; P=0.041,<0.001,<0.001). d and D ex were not correlated with ISUP grades ( P>0.05). Conclusion:t d-dMRI based microstructural mapping correlates with ISUP grades of PCa and may be useful for the differential diagnosis of csPCa.

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.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

The key role of the path planning technology for guide robots of the blind was introduced.The current research status of path planning algorithms based on traditional algorithms and intelligent algorithms was reviewed,involving in their advantages,disadvantages and application scopes and scenarios.The application of fusion algorithms in the path planning of guide robots for the blind was discussed,the challenges of the path planning algorithms of guide robots for the blind were analyzed,and its future development directions were pointed out.[Chinese Medical Equipment Journal,2025,46(2):92-101]

P53 is a key tumor suppressor gene,which is regulated in many ways.Zinc finger 148(ZNF148)and SP5,as zinc finger transcription factors(TFs),play important roles in tumor suppression and carcinogenesis.The regulatory relationship between these two TFs and p53 has not been reported.In this paper,Ishikawa and A549 cell lines with different p53 expression levels were used as research mod-els to explore the transcriptional regulation of the P53 gene by ZNF148 and SP5.The data showed that there were differences in the expression of ZNF148 and SP5 in the two cell lines.The mRNA expression of ZNF148 in Ishikawa was 1.9 times higher than that of A549,and the mRNA expression of SP5 in A549 was 802.4 times that of ZNF148.Data showed that in Ishikawa cells,the expression of P53 de-creased(81.8％)after ZNF148 knockdown,and increased(2.6 times)after SP5 overexpression.Transfection of si-SP5 and ZNF148 expression plasmids into A549 cells increased the mRNA expression of P53 by 6.6 times and 14.6 times,respectively.These results indicate that ZNF148 could activate,whereas SP5 could inhibit,P53 expression.The conserved cis-element of ZNF148 and SP5 TFs was found in the region of the P53 promoter by bioinformatics methods.The data from dual luciferase reporter gene assay showed that the luciferase activity of ZNF148 in Ishikawa and A549 cells was increased by 2.1-fold and 4.2-fold compared with the control group(P＜0.05).Compared with the control group,the normalized relative luciferase activity of transfected SP5 decreased by 77.1％and 35.7％(P＜0.05).However,when the cis-element of ZNF148 and SP5 was mutated,the effect disappeared.Further trans-fection of ZNF148 and SP5 with different ratios revealed that SP5 could reverse the transcriptional activa-tion of P53 by ZNF148.Studies have shown that ZNF148 shares a common site with SP5,and the ratio of the two TFs may influence the transcriptional activity of P53.The expression of the Wnt pathway and the cell proliferation rate after knockdown of ZNF148 and SP5 were further studied to explore the role of the two TFs.Our data show that ZNF148 and SP5 could regulate the transcriptional activity of P53,and their expression levels and interaction may be the key factors regulating P53 expression.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

Objective:To investigate the effects of pulsed electromagnetic field(PEMF)on sevoflurane-induced cognitive dysfunction in elderly rats and also explore its related mechanism.Methods:Thirty elderly male rats were randomly divided into the control group,sevoflurane treatment group(SEV),and sevoflurane+PEMF treatment group(SEV+PEMF).Rats in the sevoflurane group and sevoflurane+PEMF group passively inhaled 2.5％sevoflurane for 4 h,while rats in the SEV+PEMF group were stimulated with 2 mT,15 Hz PEMF for 14 d(2 h/day).The cognitive function of rats was evaluated via the Morris water maze testing.The serum concentrations of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β),IL-6,neuron specific enolase(NSE),and β amyloid protein(Aβ),as well as the levels of nerve growth factor(NGF)and brain-derived neurotrophic factor(BDNF)in hippocampal tissue,were de-termined via ELISA.Western blot was used to detect the expression of autophagy-related biomarkers in rat hippocampal tissue.Secondly,30 elderly male rats were randomly divided into three groups:SEV group,SEV+PEMF group,and SEV+3-MA(the autophagy inhibitor)+PEMF group.The Morris water maze experiment was used to evaluate the change of PEMF-induced improvement of cognitive function sevoflurane-inhaled elderly rats following the autophagy inhi-bition.Results:PEMF inhibited sevoflurane-induced increase in escape latency and overall swimming distance,as well as the decrease in the number of crossing target quadrant(P＜0.05);PEMF decreased the levels of serum Aβ and NSE in elderly rats inhaled with sevoflurane(P＜0.05),decreased the levels of TNF-α,IL-1β,and IL-6(P＜0.05),increased the levels of NGF and BDNF in hippocampal tissue(P＜0.05),inhibited neuronal apoptosis in hip-pocampal tissue and increased its autophagy level(P＜0.05).Following inhibition of autophagy with 3-MA,the im-provement of PEMF on the decreased learning and memory ability induced by sevoflurane in elderly rats was significantly inhibited(P＜0.05).Conclusion:PEMF can effectively inhibit sevoflurane-induced cognitive dysfunction in elderly rats by regulating the autophagy of hippocampal neuronal cells.

Aim To explore the mechanism of Jiawei Shaofu Zhuyu decoction in antagonizing endometriosis fibrosis by regulating mitophagy.Methods After the animal model was constructed,the syndrome was evalu-ated by general condition,organ water content and ther-mal imaging.The curative effect was evaluated by the weight of ectopic focus and the degree of adhesion.The pathological changes were compared using HE stai-ning,transmission electron microscopy,Masson and Sir-ius red staining.The expression of PINK1 and Parkin was detected by immunohistochemistry.The expression of mRNA and protein was determined by qPCR and Western blot,and the level of serum ROS was detected by ELISA.Results The autonomic activity of model mice was weakened,the water content of organs rose,and the temperature of limbs and lower abdomen was reduced by thermal imaging.HE staining showed obvi-ous hyperplasia of ectopic epithelium and glands.Transmission electron microscopy showed mitochondrial and endoplasmic reticulum structure damage,and nor-mal autophagy structure disappeared.Masson and Siri-us red staining showed increased collagen deposition;immunohistochemistry showed decreased expression of PINK1 and Parkin in ectopic foci.qPCR and Western blot showed that the expression of PINK1,Parkin,Bec-lin1,LC3 mRNA and protein in ectopic foci of model mice decreased,the expression of p62 mRNA and pro-tein increased,and serum ROS increased.The syn-drome performance of model mice was improved after the intervention of Jiawei Shaofu Zhuyu decoction;the inflammatory infiltration of ectopic foci was relieved,the morphology of mitochondria and endoplasmic retic-ulum was restored,and normal autophagy structure ap-peared.The degree of collagen deposition and fibrosis was reduced;the mRNA and protein expression of PINK1,Parkin,Beclin1 and LC3 increased.The ex-pression of p62 mRNA and protein decreased,and the level of ROS decreased.Conclusions Jiawei Shaofu Zhuyu decoction can improve the fibrosis of ectopic le-sions in mice with endometriosis of cold-dampness sta-sis syndrome,which may be related to the regulation of mitophagy.