ObjectiveTo explore the feasibility of constructing a programmed death receptor-1（PD-1） molecular probe for non-invasive micro-positron emission tomography/computed tomography （Micro-PET/CT） imaging of PD-1 protein in mouse S180 sarcoma. MethodsA transgenic PD-1 C57 S180 sarcoma mouse model was established using the S180 sarcoma cell injection. Furthermore， ¹²⁴I-anti-PD-1 monoclonal antibody probe was synthesized. 18.5 MBq of the ¹²⁴I-anti-PD-1 probe was injected into the tail vein of transgenic PD-1 C57 mice. Subsequently， S180 sarcoma was imaged using Micro-PET/CT. ResultsStudy successfully established a transgenic PD-1 C57 S180 sarcoma mouse model. Immunohistochemical （IHC） results showed PD-1 protein expression in S180 sarcoma. Micro-PET/CT imaging successfully visualized the PD-1 protein receptor in S180 sarcoma at different time points （20， 48， 72， and 120 h） after probe injection. ConclusionThe ¹²⁴I-anti-PD-1 monoclonal antibody molecular probe successfully targets the PD-1 receptor in S180 sarcoma of transgenic PD-1 C57 mice， and presents clear Micro-PET/CT immunoassay results， thus it potentially enables the non-invasive screening of patients with PD-1 positive malignant tumors.

Gut microbial communities are likely remodeled in tandem with accumulated physiological decline during aging, yet there is limited understanding of gut microbiome variation in advanced age. Here, we performed a metagenomics-based enterotype analysis in a geographically homogeneous cohort of 367 enrolled Chinese individuals between the ages of 60 and 94 years, with the goal of characterizing the gut microbiome of elderly individuals and identifying factors linked to enterotype variations. In addition to two adult-like enterotypes dominated by Bacteroides (ET-Bacteroides) and Prevotella (ET-Prevotella), we identified a novel enterotype dominated by Escherichia (ET-Escherichia), whose prevalence increased in advanced age. Our data demonstrated that age explained more of the variance in the gut microbiome than previously identified factors such as type 2 diabetes mellitus (T2DM) or diet. We characterized the distinct taxonomic and functional profiles of ET-Escherichia, and found the strongest cohesion and highest robustness of the microbial co-occurrence network in this enterotype, as well as the lowest species diversity. In addition, we carried out a series of correlation analyses and co-abundance network analyses, which showed that several factors were likely linked to the overabundance of Escherichia members, including advanced age, vegetable intake, and fruit intake. Overall, our data revealed an enterotype variation characterized by Escherichia enrichment in the elderly population. Considering the different age distribution of each enterotype, these findings provide new insights into the changes that occur in the gut microbiome with age and highlight the importance of microbiome-based stratification of elderly individuals.
Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Bacteroides ; China ; Diabetes Mellitus, Type 2/microbiology* ; Escherichia coli/classification* ; Gastrointestinal Microbiome/genetics* ; Metagenomics ; East Asian People

OBJECTIVES: To synthesize a temperature-responsive multimodal motion microrobot (MMMR) using temperature and magnetic field-assisted microfluidic droplet technology to achieve targeted drug delivery and controlled drug release. METHODS: Microfluidic droplet technology was utilized to synthesize the MMMR by mixing gelatin with magnetic microparticles. The microrobot possessed a magnetic anisotropy structure to allow its navigation and targeted drug release by controlling the temperature field and magnetic field. In the experiment, the MMMR was controlled to move in a wide range along a preset path by rotating a uniform magnetic field, and the local circular motion was driven by a planar rotating gradient magnetic field of different frequencies. The MMMR was loaded with simulated drugs, which were released in response to laser heating. RESULTS: Driven by a rotating magnetic field, the MMMR achieved linear motion following a predefined path. The planar gradient rotating magnetic field controlled circular motion of the MMMR with an adjustable radius, utilizing the centrifugal force generated by rotation. The drug-loaded MMMR successfully reached the target location under magnetic guidance, where the gelatin matrix was melted using laser heating for accurate drug release, after which the remaining magnetic particles were removed using magnetic field. CONCLUSIONS The MMMR possesses multimodal motion capabilities to enable precise navigation along a predefined path and dynamic regulation of drug release within the target area, thus having great potential for a wide range of biomedical applications.
Drug Delivery Systems/methods* ; Temperature ; Drug Liberation ; Magnetic Fields ; Robotics ; Gelatin/chemistry* ; Delayed-Action Preparations ; Microfluidics ; Motion

Objective: To explore the efficacy of focal radiofrequency ablation (RFA) in the treatment of low-to-intermediate risk localized prostate cancer and its impact on postoperative urinary control and sexual function recovery，in order to explore the feasibility of minimally invasive methods for the treatment of localized prostate cancer. Methods: Clinical data of 28 patients with low-to-intermediate risk localized prostate cancer who underwent RFA in Nanjing Drum Tower Hospital，Affiliated Hospital of Medical School during Jun.2017 and Feb.2021 were retrospectively analyzed.The 5-year failure-free survival (FFS) rate，surgery related complications，postoperative urinary control and sexual function were collected.The differences between the survival curves of patients in the low-risk and intermediate-risk subgroups were assessed with log-rank test and Breslow test. Results: All surgeries were successfully completed under local anesthesia.During the median follow-up of 43 (40-49) months，the 5-year FFS rate predicted by Kaplan-Meier method was 78.57%; 25 patients (89.29%) did not experience surgery-related complications; 27 patients (96.43%) were able to control urination; 1 patient developed new-onset sexual dysfunction.There was no significant difference in the survival curves between patients in the low-risk and intermediate-risk groups (P>0.05). Conclusion: RFA for patients with low-to-intermediate risk localized prostate cancer has good clinical efficacy，little impact on urinary control and sexual function recovery，and few postoperative complications，which can be used as one of the treatment options for these patients.

This study was aimed at investigating the effectiveness of various host nucleic acid removal and non-specific amplifica-tion techniques in animal tissue samples,to increase the accuracy of pathogen identification in tissue samples.Simulated samples were prepared with a mixture of mouse lung tissue homogenates and Klebsiella pneumoniae fluids,and processed with six host nucleic acid removal kits and three non-specific amplification techniques.The effectiveness of each method in removing host DNA and enriching nucleic acids of pathogenic microorganisms was evaluated through real-time fluorescence quantitative PCR and high-throughput se-quencing.For host nucleic acid removal techniques,the method of selective cleavage and quantitative degradation of host DNA(Com-plete5 kit)effectively decreased the host nucleic acid content in tissue samples and increased the relative abundance of pathogen nucleic acids.In contrast,the magnetic bead method for host DNA removal(Next microbiome DNA enrichment Kit kit)was less effec-tive.At lower pathogen concentrations(77 CFU/mL),the Vazyme kit was more effective than the other kits in removing host nucleic acids.Non-specific amplification techniques(MALBAC whole genome amplification,MDA isothermal amplification,and random primer amplification)were not applicable to tissue samples and were not effective in increasing the relative abundance of pathogen nucleic acids.Selective lysis and quantitative degradation of host DNA were suitable for processing tissue samples with high host back-ground and low pathogenic microorganism levels,whereas non-specific amplification methods were not applicable to tissue samples for pre-processing of macro-genome high-throughput sequencing.

The treatment of castration-resistant prostate cancer (CRPC) faces major challenges characterized by acquired resistance to androgen deprivation therapy (ADT) and consequent aggressive tumor progression. In this context, ubiquitination and deubiquitination modifications, as key protein post-translational modifications, play a crucial role in prostate tumourigenesis and progression. In recent years, the regulation of ubiquitination and deubiquitination in CRPC by the androgen receptor signalling pathway and the tumour microenvironment has received extensive attention, and these dynamic regulatory processes have become important molecular events driving CRPC progression by affecting the proliferation, metastasis, and immune escape ability of tumour cells. Therefore, in-depth analysis of the mechanisms of ubiquitination and deubiquitination in CRPC will help develop new therapeutic targets and provide more therapeutic options for patients.

Objective To investigate the effect of N-myc downstream regulated gene 1(NDRG1)on ferroptosis in mouse brain microvascular endothelial cells(BMVEC)induced by oxygen-glu-cose deprivation(OGD).Methods After primary BMVEC were isolated and cultured from mice,electron microscopy was used to observe the mitochondrial morphology of the cells after OGD.bEnd.3 cells were cultured and divided into six groups:control group,model group(OGD),si-NC(negative control)group,si-NDRG1(NDRG1 interference RNA)group,OGD+si-NC(negative control modeling)group,and OGD+si-NDRG1(NDRG1 interference)group(n=3).The model group,OGD+si-NC group,and OGD+si-NDRG1 group were subjected to the OGD model.Si-NC transfection was performed in the si-NC and OGD+si-NC groups,while si-NDRG1 transfection was carried out in the si-NDRG1 and OGD+si-NDRG1 groups.Cell viability,MDA,glutathione,Fe2+,lipid peroxidation levels,and protein levels of NDRG1,glutathione peroxidase 4(GPX4),and acyl-CoA synthetase long-chain family member 4(ACSL4)were detected in each group.Results Compared with the control group,the model group showed a significant reduction in the number of cells adhering to the surface after OGD treatment,swollen cytoplasm and decrease in cell viability[(37.68±2.43)％vs(96.34±12.08)％,P＜0.05],down-regulation of GPX4 and up-regulation of ACSL4 and NDRG1 expression(0.78±0.02 vs 1.15±0.01,P＜0.01;1.45±0.04 vs 0.78±0.12,P＜0.01;1.22±0.01 vs 0.13±0.01,P＜0.01).In the si-NDRG1 group,the protein levels of GPX4 and NDRG1 were significantly lower,while the protein levels of ACSL4 and gluta-thione were significantly higher than the si-NC group(P＜0.05).The OGD+si-NC group showed significantly lower GPX4 expression and glutathione level,while obviously higher NDRG1,ACSL4 expression,MDA,and relative fluorescence intensities of Fe2+and oxidized lipid levels when compared to the si-NC and si-NDRG1 groups(P＜0.05).The OGD+si-NDRG1 group showed significantly lower GPX4 expression and glutathione level,and higher ACSL4 and relative fluorescence intensity of Fe2+than the si-NC group and the si-NDRG1 group,while lower NDRG1 expression than the si-NC group but higher than the si-NDRG1 group,and lower NDRG1,ACSL4,MDA,and relative fluorescence intensities of Fe2+and oxidized lipids when compared with the OGD+si-NC group(P＜0.05).Conclusion Knockdown of NDRG1 can alleviate OGD-induced ferroptosis in microvascular endothelial cells by improving iron metabolism and lipid per-oxidation.

Objective To investigate the effect of N-myc downstream regulated gene 1(NDRG1)on ferroptosis in mouse brain microvascular endothelial cells(BMVEC)induced by oxygen-glu-cose deprivation(OGD).Methods After primary BMVEC were isolated and cultured from mice,electron microscopy was used to observe the mitochondrial morphology of the cells after OGD.bEnd.3 cells were cultured and divided into six groups:control group,model group(OGD),si-NC(negative control)group,si-NDRG1(NDRG1 interference RNA)group,OGD+si-NC(negative control modeling)group,and OGD+si-NDRG1(NDRG1 interference)group(n=3).The model group,OGD+si-NC group,and OGD+si-NDRG1 group were subjected to the OGD model.Si-NC transfection was performed in the si-NC and OGD+si-NC groups,while si-NDRG1 transfection was carried out in the si-NDRG1 and OGD+si-NDRG1 groups.Cell viability,MDA,glutathione,Fe2+,lipid peroxidation levels,and protein levels of NDRG1,glutathione peroxidase 4(GPX4),and acyl-CoA synthetase long-chain family member 4(ACSL4)were detected in each group.Results Compared with the control group,the model group showed a significant reduction in the number of cells adhering to the surface after OGD treatment,swollen cytoplasm and decrease in cell viability[(37.68±2.43)％vs(96.34±12.08)％,P＜0.05],down-regulation of GPX4 and up-regulation of ACSL4 and NDRG1 expression(0.78±0.02 vs 1.15±0.01,P＜0.01;1.45±0.04 vs 0.78±0.12,P＜0.01;1.22±0.01 vs 0.13±0.01,P＜0.01).In the si-NDRG1 group,the protein levels of GPX4 and NDRG1 were significantly lower,while the protein levels of ACSL4 and gluta-thione were significantly higher than the si-NC group(P＜0.05).The OGD+si-NC group showed significantly lower GPX4 expression and glutathione level,while obviously higher NDRG1,ACSL4 expression,MDA,and relative fluorescence intensities of Fe2+and oxidized lipid levels when compared to the si-NC and si-NDRG1 groups(P＜0.05).The OGD+si-NDRG1 group showed significantly lower GPX4 expression and glutathione level,and higher ACSL4 and relative fluorescence intensity of Fe2+than the si-NC group and the si-NDRG1 group,while lower NDRG1 expression than the si-NC group but higher than the si-NDRG1 group,and lower NDRG1,ACSL4,MDA,and relative fluorescence intensities of Fe2+and oxidized lipids when compared with the OGD+si-NC group(P＜0.05).Conclusion Knockdown of NDRG1 can alleviate OGD-induced ferroptosis in microvascular endothelial cells by improving iron metabolism and lipid per-oxidation.

Objective To investigate the diagnostic efficacy of targeted biopsy(TB)combined with ipsilateral hemiglandular systematic biopsy(SB)of the dominant lesion,so as to explore a novel reduced-core biopsy strategy.Methods A retrospective analysis was conducted on the clinical data of 299 patients treated in our hospital during Sep.1,2022,and Feb.28,2023,who had a Prostate Imaging Reporting and Data System(PI-RADS)score ≥3 and underwent combined TB and SB.The dominant lesion was defined as the lesion with the highest PI-RADS score on multi-parametric magnetic resonance imaging(mpMRI);in cases of identical scores,the largest was designated as the dominant.SB was categorized as ipsilateral(ipsi-SB)or contralateral(contra-SB)to the dominant lesion.The consistency in detecting clinically significant prostate cancer(csPCa)was compared between TB with ipsi-SB(TB+ipsi-SB),TB with contra-SB(TB+contra-SB),and TB with SB(TB+SB).Subgroup analyses were performed based on PI-RADS score,prostate-specific antigen(PSA)level,prostate volume(PV),and mpMRI lesion distribution to evaluate csPCa detection rates across different variables.Results TB+ipsi-SB demonstrated comparable detection rate to TB+SB(46.2％vs.46.8％).The K values for TB+ipsi-SB and TB+contra-SB relative to TB+SB were 0.987(95％CI:0.969-1.000,P＜0.01)and 0.933(95％CI:0.892-0.974,P＜0.01),respectively.Across all subgroups,TB+ipsi-SB showed the highest agreement with TB+SB.Notably,in subgroups with PI-RADS 3 and 5,PSA＞0-20 ng/mL,PV＜25 mL,bilateral or multiple mpMRI lesions,TB+ipsi-SB achieved complete concordance with TB+SB in csPCa detection[K=1.000(95％CI:1.000-1.000),P＜0.01].Conclusion For patients with PI-RADS score ≥3,TB+ipsi-SB exhibits near-perfect consistency with TB+SB in csPCa detection while requiring fewer biopsy cores.TB+ipsi-SB represents a promising refinement of the TB+SB approach.

This report described a periviable extremely preterm infant who received Nirsevimab before discharge for preventing respiratory syncytial virus infection. The infant was born at 22?3 weeks' gestation with a birth weight of 360 g. Nirsevimab was administered on January 12, 2025 (110 days after birth, corrected gestational age of 38?2 weeks) at the Women and Children's Medical Center of Southern Medical University (Shenzhen Maternity & Child Healthcare Hospital). No local or systemic adverse reactions were observed following administration. Follow-up until 1 year and 2 months of age (November 2025) revealed no occurrence of respiratory syncytial virus infection.