The molecular mechanisms underlying the develop-ment and metastasis of prostate cancer remain elusive.This comprehensive review delves into the intricate role of cofilin,an actin-binding protein,in the pathogenesis and progression of prostate cancer.Cofilin is a significant protein in cytoskeletal dynamics,and any dysregulation may result in the morphological changes in normal cells and the invasion and metastasis of tumor cells.Research has revealed that the activity of cofilin is regula-ted by various mechanisms,including phosphorylation/dephos-phorylation and interactions with other molecules.Moreover,this review discusses promising therapeutic interventions,such as co-filin inhibitors and gene therapy,which have demonstrated effica-cy in preclinical models.The challenge of clinically preventing the transition to castration-resistant prostate cancer and tumor metastasis is widely recognized,necessitating the development of precise drug treatments and biomarker identification.As a key regulatory protein,cofilin provides a more comprehensive refer-ence for the prevention and treatment of prostate diseases.

Objective:To summarize the experience of diagnosis and treatment of unexplained neonatal intestinal perforation.Methods:A case summary was conducted.Intestinal perforation children who showed unclear etiology during surgical exploration in Fujian Children′s Hospital from October 2017 to October 2023 were retrospectively analyzed.The perforation characteristics, pathological characteristics, etiological analysis and surgical methods were analyzed, and the diagnosis and treatment experience was summarized.Results:There were 21 neonates with unexplained intestinal perforation, including 15 boys and 6 girls.There were more full-term infants (12 cases) than preterm ones (9 cases), and more neonates with normal birth weight (12 cases) than those with low birth weight (9 cases).Intraoperative perforation was detected in the ileum in 13 cases and colon in 8 cases.The perforation diameter ranged between 0.5-2.0 cm.Single perforation was detected in 20 cases, and 1 case had two perforations.All patients underwent full-layer multipoint biopsy and enterostomy.Pathological reports after surgery showed that Hirschsprung disease was confirmed in 10 cases, and Hirschsprung disease allied disorders were diagnosed in 8 cases.The remaining 3 cases had normal ganglion cells, and 2 cases of them had spontaneous intestinal perforation, and 1 case had meconium ileus.After operation, 3 cases gave up treatment, 1 case died, and 17 patients were discharged from hospital at the first stage.Nine cases with Hirschsprung disease received radical surgery at the age of 3-6 months.Six out of 8 patients with Hirschsprung disease allied disorders underwent fistula closure surgery after accurate evaluation.Among the 6 children who received fistula closure surgery, 1 case underwent Santulli enterostomy because of inability to defecate and abdominal distension after surgery.Two of the 6 children undergoing fistula closure surgery were still being followed up.Two cases of spontaneous intestinal perforation and 1 case of meconium ileus underwent fistula closure surgery at the age of 3 months, and postoperative defecation was normal.Conclusions:Intestinal neuronal dysplasia, meconium ileus combined with intestinal perforation and spontaneous intestinal perforation should be considered in unexplained neonatal intestinal perforation.It is recommended that enterostomy and multipoint biopsy should be performed to clarify the pathology before further treatment in children with unexplained intestinal perforation.Santulli enterostomy is a feasible staging operation.

Objective To identify potential biomarkers for proliferative diabetic retinopathy(PDR)using proteomics and transcriptomics data.Methods In this study,the proteomics dataset(PXD046630)and two transcriptomics datasets(GSE60436 and GSE102485)were derived from the aqueous humor samples and fibrovascular membranes of PDR patients,respectively.Differentially expressed genes(DEGs)were identified via R software,specifically the limma and edgeR pack-ages.The shared DEGs between PXD046630 and GSE60436 were analyzed via protein-protein interaction(PPI),Gene On-tology(GO)enrichment,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.The key DEGs were validated in GSE102485 via receiver operating characteristic(ROC)curve analysis.A quantitative polymerase chain reaction(qPCR)assay was used to confirm the mRNA of these candidate biomarkers in human retinal microvascular endothelial cells(HRMECs)cultured in high glucose and low oxygen conditions.Results A total of 59 shared DEGs and 26 hub genes were identified from the PXD046630 and GSE60436 datasets.KEGG analysis revealed that six pathways,inclu-ding extracellular matrix-receptor interaction,proteoglycans in cancer,and complement and coagulation cascades,were enriched in 12 key DEGs.Fibronectin 1(FN1),tissue inhibitor of metalloproteinase 3(TIMP3),complement factor H(CFH),decorin(DCN),and lipoprotein receptor-related protein-2(LRP2)were identified as potential biomarkers on the basis of their AUC values being greater than 0.900(CI≥95％).The mRNA expression levels of FN1,CFH,and LRP2 were significantly increased in HRMECs cultured in high glucose and low oxygen conditions.Conclusion FN1,CFH,and LRP2 are potential biomarkers for PDR,and further studies are needed to explore their roles and therapeutic potential in PDR.

Objective : To develop and to validate a combined model integrating18F-FDG PET/CT radiomics with clinical features to distinguish between lymphoma and lymphoid inflammatory hyperplasia. Methods : A retrospective study was conducted on a cohort of 232 patients diagnosed with lymphoma or lymphoid inflammatory hyperplasia. Comparative analyses of clinical and traditional imaging indicators were performed to identify inter-group differences. The clinical features were delineated and extracted using medical software including 3D-Slicer and Lifex. Selection of the features was performed to construct a PET/CT-based radiomics Logistic model, with a combined model integrating PET/CT with clinical features then used to evaluate the discriminative efficacy of these models. Results: Analysis of inter-group differences indicated that age, CTmean, and metabolic tumor volume(MTV)were effective for differentiating between lymphoma and lymphoid inflammatory hyperplasia(P<0.05). The PET/CT-based radiomics Logistic model differentiated between lymphoma and lymphoid inflammatory hyperplasia, with an area under curve(AUC) of 0.924(95%CI: 0.884-0.960) and 0.863(95%CI: 0.774-0.939) in the training and testing cohorts, respectively. The integrated Logistic model that combined PET/CT-based radiomics with clinical features to distinguish between lymphoma and lymphoid inflammatory hyperplasia achieved an AUC of 0.933(95%CI: 0.889-0.969) in the training cohort and 0.884(95%CI: 0.792-0.964) in the testing cohort. Decision curve analysis(DCA) demonstrated that the integrated model provided the greatest clinical net benefit. Conclusion The hybrid model integrating18F-FDG PET/CT radiomics with clinical features shows robust diagnostic efficacy to distinguish between lymphoma and lymphoid inflammatory hyperplasia.

Objective: To identify an optimal back-flush solution for leukocyte-depleted filters that maximizes peripheral blood mononuclear cell (PBMC) recovery with high viability, long-term storage stability, and sterility of the harvested residues, thereby providing a clinically translatable strategy. Methods: Three sterile bag-packaged solutions—Saline, Solvent, and Hanks' balanced salt solution (HBSS)—were used to back-flush randomly assigned leukocyte-depleted filters. Nucleated cell recovery rate and viability of the harvested residues were compared. The optimal solution identified was applied to an expanded sample set. PBMC viability and yield were evaluated after 1h vs 48h storage of the residues. PBMCs isolated from the residues were cryopreserved in liquid nitrogen for 1 month, followed by post-thaw comparisons of viability and T-cell expansion capacity. Results: The Solvent group achieved the highest and most consistent nucleated cell recovery rate. Post-flush recovery rate from filters after 400 mL whole blood processing was (21.3±1.6)% for the Solvent group, significantly higher than Saline group (19.2±6.3)% and HBSS group (11.2±5.0)%, with residues from all groups maintaining viability >90%. No biologically significant difference in residue viability was observed between 48h vs 1h storage groups (93.3±2.3)% vs (95.7±1.8)%). PBMC recovery rates from residues showed no statistical difference between 48h vs 1h storage groups [(48.2%±9.5%)vs (40.41%±8.35%), P>0.05], with (17.7±2.6)×10 cells. After 1-month cryopreservation and 10-day expansion, PBMCs isolated from 48-hour-stored residues retained (91.2±3.2)% viability and achieved a (61.9±15.9)-fold expansion. Conclusion: The bag-packaged Solvent, as a back-flush solution, enables sterile acquisition of leukocyte-depleted filter residues through closed-system tubing connections. These residues maintained PBMC viability and recovery rates after 48h storage at 2℃-8℃, with post-cryopreservation (1-month liquid nitrogen) viability and expansion capacity remaining stable. This protocol complies with blood bank regulatory criteria, addresses the concerns about the infectious window period in cell therapy raw materials, and provides a clinically translatable strategy for PBMC-based applications.

OBJECTIVE: Several epidemiological observational studies have related particulate matter (PM) exposure to Inflammatory bowel disease (IBD), but many confounding factors make it difficult to draw causal links from observational studies. The objective of this study was to explore the causal association between PM _2.5 exposure, its absorbance, and IBD. METHODS: We assessed the association of PM _2.5 and PM _2.5 absorbance with the two primary forms of IBD (Crohn's disease [CD] and ulcerative colitis [UC]) using Mendelian randomization (MR) to explore the causal relationship. We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study. Single-nucleotide polymorphisms linked with PM _2.5 concentrations or their absorbance were used as instrumental variables (IVs). We used inverse variance weighting (IVW) as the primary analytical approach and four other standard methods as supplementary analyses for quality control. RESULTS: The results of MR demonstrated that PM _2.5 had an adverse influence on UC risk (odds ratio [ OR] = 1.010; 95% confidence interval [ CI] = 1.001-1.019, P = 0.020). Meanwhile, the results of IVW showed that PM _2.5 absorbance was also causally associated with UC ( OR = 1.012; 95% CI = 1.004-1.019, P = 0.002). We observed no causal relationship between PM _2.5, PM _2.5 absorbance, and CD. The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy, ensuring the reliability of MR results. CONCLUSION Based on two-sample MR analyses, there are potential positive causal relationships between PM _2.5, PM _2.5 absorbance, and UC.
Humans ; Mendelian Randomization Analysis ; Particulate Matter/analysis* ; Polymorphism, Single Nucleotide ; Inflammatory Bowel Diseases/genetics* ; Air Pollutants/analysis* ; Crohn Disease/genetics* ; Colitis, Ulcerative/genetics* ; Genome-Wide Association Study ; Risk Factors ; Environmental Exposure

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

Objective To carry out a dynamic simulation analysis on the surgical process of the surgical robot for pedicle screw placement so as to enhance the safety of the procedure.Methods Firstly,the process of pedicle screw placement were analyzed to determine the three typical force conditions during pedicle screw track drilling including no-load condition,bone layer switching condition and spine dynamic displacement condition.Secondly,a virtual protype model of the surgical robot for pedicle screw placement was constructed with the automated dynamic analysis of mechanical systems(ADAMS).Finally,the dynamic characteristics of the surgical robot were simulated and analyzed with considerations on the three typical force conditions.Results The driving torque of the robot joints was sensitive to the load applied to the end of the opener mechanism under a wide range of operating conditions.Conclusion The surgical robot meets the requirements for pedicle screw placment,and a new idea is provided for enhancing the accuracy of pedicle screw placement.[Chinese Medical Equipment Journal,2025,46(8):32-37]