Predicting recurrence of non-muscle invasive bladder urothelial carcinoma: predictive value of the optimal cut-off value of Ki67

ObjectiveTo investigate the optimal cut-off value of immunohistochemical marker Ki67 as a prognostic factor to predict the recurrence of non-muscle invasive bladder urothelial carcinoma (NMIBUC).MethodsA total of 331 patients diagnosed with NMIBUC who underwent surgery in the Yongchuan Hospital and the Second Affiliated Hospital of Chongqing Medical University from January 2012 to January 2020 were finally included in this study. The optimal cut-off value of Ki67 for predicting recurrence of NMIBUC was calculated by ROC curve and Youden index. According to the cut-off value, the patients were divided into high ratio group and low ratio group, and the clinicopathological data of the two groups were compared. Univariate and multivariate regression analysis were used to analyze the relationship between the expression of Ki67 and postoperative recurrence of NMIBUC. The Kaplan-Meier curve was used for survival analysis.Results18% is the optimal cut-off value of Ki67 for predicting postoperative recurrence of NMIBUC. High Ki67 expression (Ki67>18%) was significantly correlated with tumor stage (P=0.001), tumor grade (P=0.014), immediate postoperative instillation (P=0.001), the expression of P53 (P=0.019) and CK20 (P=0.001). Ki67 expression greater than 18% was an independent risk factor for high recurrence rate of NMIBUC (P=0.001). Moreover, the 1-year and 3-year recurrence-free survival (RFS) of the high Ki67 group were 56.6% (95%CI 51.2%-62%) and 43.6% (95%CI 37.5%-49.7%) respectively, which were significantly lower than those in low Ki67 group which present as 92.9% (95%CI 89.0%-96.8%) and 88.3% (95%CI 82.4%-94.2%) respectively, and the difference was statistically significant (P<0.001).Conclusions18% is the optimal cut-off value of Ki67 for predicting recurrence of NMIBUC. Ki67>18% is an independent risk factor for high recurrence rate of NMIBUC. This cut-off value can more accurately predict the risk of recurrence and has the potential clinical value for guiding the postoperative adjuvant treatment and follow-up strategy of NMIBUC

Roles of cerebrospinal fluid-contacting neurons as potential neural stem cells in the repair and regeneration of spinal cord injuries

Cerebrospinal fluid-contacting neurons (CSF-cNs) represent a distinct group of interneurons characterized by their prominent apical globular protrusions penetrating the spinal cord’s central canal and their basal axons extending towards adjacent cells. Identified nearly a century back, the specific roles and attributes of CSF-cNs have just started to emerge due to the historical lack of definitive markers. Recent findings have confirmed that CSF-cNs expressing PKD2L1 possess attributes of neural stem cells, suggesting a critical function in the regeneration processes following spinal cord injuries. This review aims to elucidate the molecular markers of CSF-cNs as potential neural stem cells during spinal cord development and assess their roles post-spinal cord injury, with an emphasis on their potential therapeutic implications for spinal cord repair

Nontargeted and targeted metabolic profile of metabolic syndrome patients: a study based on Yi and Han populations in Yunnan

ObjectiveUltra-high-performance liquid chromatography-time-of-flight mass spectrometry (UHPLC-TOF-MS) was employed to analyze serum metabolites and metabolic pathways associated with metabolic syndrome (MS) in the Yi and Han populations of Yunnan.MethodsParticipants included individuals diagnosed with MS and healthy controls from the Yi and Han populations of Yunnan. Serum nontargeted and amino acid-targeted metabolomics analyses were conducted to identify differential serum metabolites (DEMs) and metabolic pathways associated with MS pathogenesis in these two ethnic groups.ResultsNontargeted metabolomics analysis revealed 2,762 DEMs in the MS group of the Han population, while 1,535 DEMs were identified in the MS group of the Yi population [variable importance in projection (VIP)>1, P<0.05]. Venn analysis highlighted common and unique DEMs between the two populations. KEGG pathway analysis identified seven significantly enriched pathways in the Han group and five in the Yi group, primarily involving amino acid synthesis and metabolism. To investigate the role of amino acids in MS, serum levels of 71 endogenous amino acids were quantified. In the MS group of the Han population, 19 differential amino acids were identified, significantly enriched in pathways related to D-glutamine and D-glutamate metabolism, as well as cysteine and methionine metabolism. In the Yi population, six differential amino acids were identified, with significant enrichment in D-glutamine and D-glutamate metabolism, sulfur metabolism, and valine, leucine, and isoleucine biosynthesis.ConclusionOur study investigates metabolic differences in metabolic syndrome (MS) between Yi and Han populations through nontargeted and targeted metabolomics approaches, identifying both common and unique metabolites and metabolic pathways associated with MS, especially amino acid metabolic disorders, including glycine, serine, and threonine metabolism, D-glutamine and D-glutamate metabolism, which may play critical roles in regulating different metabolic dysfunctions and worth further exploration in MS pathogenesis, which might provide insights for the effective prevention and treatment of MS in various populations

Bacteroides acidifaciens and its derived extracellular vesicles improve DSS-induced colitis

Introduction“Probiotic therapy” to regulate gut microbiota and intervene in intestinal diseases such as inflammatory bowel disease (IBD) has become a research hotspot. Bacteroides acidifaciens, as a new generation of probiotics, has shown beneficial effects on various diseases.MethodsIn this study, we utilized a mouse colitis model induced by dextran sodium sulfate (DSS) to investigate how B. acidifaciens positively affects IBD. We evaluated the effects ofB. acidifaciens, fecal microbiota transplantation, and bacterial extracellular vesicles (EVs) on DSS-induced colitis in mice. We monitored the phenotype of mouse colitis, detected serum inflammatory factors using ELISA, evaluated intestinal mucosal barrier function using Western blotting and tissue staining, evaluated gut microbiota using 16S rRNA sequencing, and analyzed differences in EVs protein composition derived from B. acidifaciens using proteomics to explore how B. acidifaciens has a positive impact on mouse colitis.ResultsWe confirmed that B. acidifaciens has a protective effect on colitis, including alleviating the colitis phenotype, reducing inflammatory response, and improving intestinal barrier function, accompanied by an increase in the relative abundance of B. acidifaciens and Ruminococcus callidus but a decrease in the relative abundance of B. fragilis. Further fecal bacterial transplantation or fecal filtrate transplantation confirmed the protective effect of eosinophil-regulated gut microbiota and metabolites on DSS-induced colitis. Finally, we validated that EVs derived from B. acidifaciens contain rich functional proteins that can contribute to the relief of colitis.ConclusionTherefore, B. acidifaciens and its derived EVs can alleviate DSS-induced colitis by reducing mucosal damage to colon tissue, reducing inflammatory response, promoting mucosal barrier repair, restoring gut microbiota diversity, and restoring gut microbiota balance in mice. The results of this study provide a theoretical basis for the preclinical application of the new generation of probiotics

Study on Surface Hardness and Microstructure of Pure Copper Chip Strips Prepared by LSEM

Large strain extrusion machining (LSEM) is one of the severe plastic deformation (SPD) methods that can improve the mechanical properties of materials. The purpose of this experiment is to study the surface hardness and microstructure of the pure copper chip strips. It was found that most of the grains of the chip strips had been refined to the ultrafine grain grade. Finite element analysis (FEA) simulations were conducted to predict the von Mises equivalent strains. Based on the analysis of variance (ANOVA), further study indicated that the surface hardness of the chip strips was decided by several key parameters including the chip thickness compression ratio, rake angle, and uncut chip thickness during LSEM. Through this analysis, a set of parameters which have the greatest impact on the properties of the material can be found. This set of parameters helps us to achieve the strip with the best performance

Study on Surface Hardness and Microstructure of Pure Copper Chip Strips Prepared by LSEM

Large strain extrusion machining (LSEM) is one of the severe plastic deformation (SPD) methods that can improve the mechanical properties of materials. The purpose of this experiment is to study the surface hardness and microstructure of the pure copper chip strips. It was found that most of the grains of the chip strips had been refined to the ultrafine grain grade. Finite element analysis (FEA) simulations were conducted to predict the von Mises equivalent strains. Based on the analysis of variance (ANOVA), further study indicated that the surface hardness of the chip strips was decided by several key parameters including the chip thickness compression ratio, rake angle, and uncut chip thickness during LSEM. Through this analysis, a set of parameters which have the greatest impact on the properties of the material can be found. This set of parameters helps us to achieve the strip with the best performance.</jats:p

[N,N-Bis(2,6-diisopropylphenyl)pent-2-ene-2,4-diiminato(1&amp;#8722;)]bis(1,2,4-diazaphosphol-1-yl)aluminium(III)

In the title compound, [Al(C29H41N2)(C2H2N2P)2], the AlIII atom is coordinated by four N atoms from &amp;#946;-diketiminate and 1,2,4-diazaphospholide ligands in a slightly distorted tetrahedral fashion