Search

Objective To identify hub genes associated with ferroptosis in the progression of diabetic nephropathy （DN） through bioinformatics analysis， offering novel insights into DN treatment. Methods Differentially expressed genes （DEGs） in DN were screened using RNA sequencing dataset GSE142025， and Gene Ontology （GO） and Gene Set Enrichment Analysis （GSEA） were utilized for functional annotation. Subsequently， the Weighted Gene Co-expression Network Analysis （WGCNA）was conducted to pinpoint key genes. Venn diagrams aided in identifying hub genes among ferroptosis-related genes （FRGs） common to DEGs and key genes. ROC curves were employed to assess the clinical diagnostic potential of these hub genes. Immunohistochemistry （IHC）was conducted to detect the expression levels of hub genes in DN patients and normal kidney tissues. Results 1 916 DEGs were identified between the DN and control （NC） groups. GO enrichment analysis revealed that DEGs were mainly involved in inflammation-related biological processes. GSEA analysis found significant enrichment in processes related to iron ion binding. Among 12 co-expression modules constructed by WGCNA， grey60， turquoise， and grey modules showed the highest correlation with DN. 188 key genes were selected from 3 modules based on the screening criteria， among which 2 were FRGs shared by DEGs， namely ceruloplasmin （CP） gene and lipocalin-2 （LCN2） gene. ROC curves confirmed high clinical diagnostic value of these two genes. IHC results showed upregulated expression of both two genes in DN patient samples （both P < 0.05）， consistent with the findings of bioinformatics analysis. Conclusion CP and LCN2 could be involved in the progression of DN by inhibiting ferroptosis， serving as promising biomarkers and treatment targets for DN.

This study aimed to investigate spontaneous hypothermia among emergency trauma patients and develop a predictive model. A cohort of 162 emergency trauma patients was categorized into hypothermic (n = 61) and control (n = 101) groups, with trauma severity assessed using the modified Glasgow Coma Scale (GCS). Univariate analysis revealed significant differences between the groups in trauma severity, posture, garment wetness, warming measures, pre-hospital fluid resuscitation, and modified GCS scores (P < 0.05). The hypothermic group exhibited lower prothrombin time compared to the control group (P < 0.05). A logistic regression model was constructed, expressed as Y = 25.76 − 1.030X 1 + 0.725X 2 + 0.922X 3 − 0.750X 4 − 0.57X 6, and its fit was evaluated using the Hosmer–Lemeshow test. The receiver operating characteristic curve demonstrated an area under the curve of 0.871, with 81.2% sensitivity and 79.5% specificity. The Youden index identified the optimal predictive cut-off at its highest (0.58). Validation results included 86.21% sensitivity, 82.93% specificity, and 84.29% accuracy. Risk factors for spontaneous hypothermia after emergency trauma encompassed trauma severity, posture during consultation, clothing dampness upon admission, warming measures during transfer, pre-hospital fluid resuscitation, and modified GCS scores. The risk prediction model demonstrated high accuracy, enabling effective assessment of spontaneous hypothermia risk in emergency trauma patients and facilitating preventive measures.

BackgroundSextupoles are an important component of storage ring octonal unit in high energy synchrotron radiation sources. They require complex technological processes and precise center extraction. Therefore, it is necessary to find out the most reasonable calibration scheme for the mechanical center.PurposeThis study aims at the calibration scheme for the mechanical center extraction of high energy photon Ssurce (HEPS) sextupoles, and obtaining the corrected mechanical central coordinate system.MethodsThe method of directly measuring the reference plane of the sextupole was adopted for the mechanical center calibration of magnets. By rotating the conventional calibration coordinate system with a given pole seam deviation angle, the three polar seam surfaces were brought closer to the theoretical positions to decrease the main diagonal component of the sextupoles. The mechanical center calibrations were performed twice for each hexacode iron to further reduce the impact of the polar seam error.ResultsThe calibration results show that the calibration repeat accuracy is 0.005 mm for the sextupole. The standard deviation between the measured value and the design value of the pole seam spacing is 0.015 mm. Additionally, the standard deviation of the reference point before and after the rotation of the coordinate system is 0.09 mm, with a maximum rotation angle of 0.6 mrad.ConclusionsThe calibration scheme of this study can be used to improve the calibration accuracy and provide reference for the calibration of similar equipment. It ensures smooth installation of accelerator devices and is of significant importance for accelerator collimation measurements.

Early diagnosis of renal cell carcinoma relies on imaging tests such as ultrasound, computed tomography, or magnetic resonance imaging. Since surgery is associated with a favorable prognosis, the standard treatment for clinically limited renal cell carcinoma remains surgical resection. Among asymptomatic patients with localized renal cell carcinoma, a small number refuse surgical treatment and survive. We report a case involving a 59-year-old female who underwent a difficult radical nephrectomy 17 years after being diagnosed with malignant tumors due to primary renal cell carcinoma.

Abstract Background The MYH3‐associated myosinopathies comprise a spectrum of rare neuromuscular disorders mainly characterized by distal arthrogryposis with or without other features like pterygia and vertebrae fusion. CPSKF1B (contractures, pterygia, and spondylocarpotarsal fusion syndrome1B) is the only known autosomal recessiveMYH3‐associated myosinopathy so far, with no more than two dozen cases being reported. Materials and Methods A boy with CPSKF1B was recruited and subjected to a comprehensive clinical and imaging evaluation. Genetic detection with whole‐exome sequencing (WES) was performed on the patient and extended family members to identify the causative variation. A series of in silico and in vitro investigations were carried out to verify the pathogenicity of the two variants of the identified compound heterozygous variation. Results The patient exhibited moderate CPSKF1B symptoms including multiarticular contractures, webbed neck, and spondylocarpotarsal fusion. WES detected a compound heterozygous MYH3 variation consisting of two variants, namely NM_002470.4: c.3377A>G; p. (E1126G) and NM_002470.4: c.5161‐2A>C. It was indicated that the NM_002470.4: c.3377A>G; p. (E1126G) variant mainly impaired the local hydrogen bond formation and impacted the TGF‐B pathway, while the NM_002470.4: c.5161‐2A>C variant could affect the normal splicing of pre‐mRNA, resulting in the appearance of multiple abnormal transcripts. Conclusions The findings of this study expanded the mutation spectrum of CPSKF1B, provided an important basis for the counseling of the affected family, and also laid a foundation for the functional study of MYH3 mutations.

Abstract Background Several proteins in the tripartite-motif (TRIM) family are associated with the development of colorectal cancer (CRC), but research on the role of TRIM69 was lacking. The present study examined the correlation between TRIM69 expression and colon adenocarcinoma (COAD). Methods mRNA sequencing data for COAD patients was extracted from The Cancer Genome Atlas to analyze correlations between TRIM69 expression and patients’ clinical features as well as survival. Potential associations with immune cells and chemosensitivity also were predicted using various algorithms in the TIMER, Limma, clusterProfiler, GeneMANIA, and Gene Set Cancer Analysis platforms. Subsequently, polymerase chain reaction analysis and immunohistochemical staining were used to detect TRIM69 expression in COAD tissue samples from real-world patients. Results TRIM69 expression was lower in COAD tissues than in normal tissues and correlated with the pathologic stage and metastasis (M category). Additionally, TRIM69 was found to be involved in several immune-related pathways, notably the NOD-like signaling pathway. These results suggest that high TRIM69 expression has the potential to enhance tumor sensitivity to 5-fluorouracil and programmed cell death protein 1 (PD-1) blockers. Conclusions From our findings that TRIM69 expression was significantly reduced in COAD compared with non-cancer tissues and associated with pathologic stage and metastasis, we conclude that increasing TRIM69 expression and/or activity may help to improve therapeutic outcomes. Accordingly, TRIM69 represents a potentially valuable marker of metastasis and target for adjuvant therapy in COAD.

Objective To identify key genes in the peripheral blood of diabetic nephropathy （DN） patients based on weighted gene co-expression network analysis （WGCNA），aiming to explore the pathogenesis of DN and provide new insights into the incidence and development of DN. Methods In this study，the dataset GSE142153 was downloaded from the Gene Expression Omnibus （GEO） database to screen the differentially expressed genes （DEGs）. Then，Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was employed to investigate the molecular biological processes of these DEGs. Key modules and hub genes were identified by constructing WGCNA. The validation dataset GSE65561 was applied to analyze the receiver operating characteristic （ROC） curve to validate the potential clinical diagnostic value of hub genes. Subsequently，RT-qPCR was adopted to detect the relative expression levels of hub genes in the peripheral blood of DN patients. Results There were 23 patients with DN and 10 healthy controls in the dataset GSE142153. According to the screening criteria，there were 181 DEGs in the DN group，of which 106 DEGs were up-regulated and 75 were down-regulated. KEGG enrichment analysis mainly showed the activation of inflammatory pathways，such as interleukin （IL）-17，nuclear factor-κB （NF-κB），and JAK-STAT signaling pathways. Sixteen modules were identified by WGCNA and the turquoise module was considered to have the most clinical significance for DN. The genes in the turquoise module were selected to intersect with DEGs and IL-17 signaling pathway-related genes to obtain 5 hub genes including Chemokine （C-C motif） ligand 20 （CCL20），IL-1B，CXCL1，matrix metalloproteinase-9 （MMP-9） and Fos-like antigen 1 （FOSL1）. The results of RT-qPCR of the peripheral blood of DN patients were consistent with the bioinformatic analysis. Conclusion The hub genes，such as CCL20，may play a key role in promoting the inflammatory progression of DN through regulating the IL-17 signaling pathway，which contribute to identifying potential biomarkers and therapeutic targets for DN.

Abstract Objective: To investigate the association between folate levels and the risk of gestational diabetes mellitus (GDM) risk during the whole pregnancy. Design: In this retrospective cohort study of pregnant women, serum folate levels were measured before 24 gestational weeks (GW). GDM was diagnosed between 24th and 28th GW based on the criteria of the International Association of Diabetes and Pregnancy Study Groups. General linear models were performed to examine the association of serum folate with plasma glucose (i.e. linear regressions) and risk of GDM (i.e. log-binomial regressions) after controlling for confounders. Restricted cubic spline regression was conducted to test the dosage–response relationship between serum folate and the risk of GDM. Setting: A sigle, urban hospital in Shanghai, China. Participants: A total of 42 478 women who received antenatal care from April 2013 to March 2017 were included. Results: Consistent positive associations were observed between serum folate and plasma glucose levels (fasting, 1-h, 2-h). The adjusted relative risks (RR) and 95 % CI of GDM across serum folate quartiles were 1·00 (reference), 1·15 (95 % CI (1·04, 1·26)), 1·40 (95 % CI (1·27, 1·54)) and 1·54 (95 % CI (1·40, 1·69)), respectively (P-for-trend < 0·001). The positive association between serum folate and GDM remained when stratified by vitamin B12 (adequate v. deficient groups) and the GW of serum folate measurement (≤13 GW v. >13 GWs) Conclusions: The findings of this study may provide important evidence for the public health and clinical guidelines of pregnancy folate supplementation in terms of GDM prevention.

Background Although surgical methods are the most effective treatments for colon adenocarcinoma (COAD), the cure rates remain low, and recurrence rates remain high. Furthermore, platelet adhesion-related genes are gaining attention as potential regulators of tumorigenesis. Therefore, identifying the mechanisms responsible for the regulation of these genes in patients with COAD has become important. The present study aims to investigate the underlying mechanisms of platelet adhesion-related genes in COAD patients. Methods The present study was an experimental study. Initially, the effects of platelet number and related genomic alteration on survival were explored using real-world data and the cBioPortal database, respectively. Then, the differentially expressed platelet adhesion-related genes of COAD were analyzed using the TCGA database, and patients were further classified by employing the non-negative matrix factorization (NMF) analysis method. Afterward, some of the clinical and expression characteristics were analyzed between clusters. Finally, least absolute shrinkage and selection operator regression analysis was used to establish the prognostic nomogram. All data analyses were performed using the R package. Results High platelet counts are associated with worse survival in real-world patients, and alternations to platelet adhesion-related genes have resulted in poorer prognoses, based on online data. Based on platelet adhesion-related genes, patients with COAD were classified into two clusters by NMF-based clustering analysis. Cluster2 had a better overall survival, when compared to Cluster1. The gene copy number and enrichment analysis results revealed that two pathways were differentially enriched. In addition, the differentially expressed genes between these two clusters were enriched for POU6F1 in the transcription factor signaling pathway, and for MATN3 in the ceRNA network. Finally, a prognostic nomogram, which included the ALOX12 and ACTG1 genes, was established based on the platelet adhesion-related genes, with a concordance (C) index of 0.879 (0.848–0.910). Conclusion The mRNA expression-based NMF was used to reveal the potential role of platelet adhesion-related genes in COAD. The series of experiments revealed the feasibility of targeting platelet adhesion-associated gene therapy.

While education technology has been widely used in classrooms, and considerable investments have been made to support its use in the UK, the evidence base for many such rapidly changing technologies is weak, and their efficacy is unclear. The aim of this paper is to systematically review and synthesise empirical research on the use of technology in formative assessment, to identify approaches that are effective in improving pupils' learning outcomes. The review involved a search of 11 major databases, and included 55 eligible studies. The results suggest promising evidence that digitally delivered formative assessment could facilitate the learning of maths and reading for young children, but there is no good evidence that it is effective for other subjects, or for older children, or that it is any more effective than formative assessment without technology. The review found no good evidence that learner response systems work in enhancing children's academic attainment, and there is no evidence supporting the effectiveness of such technologies that embed gaming features. Much research in this area is of poor quality. More rigorous studies using causal designs are thus urgently needed. Meantime, there should be no rush to use technology on the basis of improving attainment.

Objective To screen and analyze the differentially-expressed genes （DEGs） of diabetic nephropathy （DN） by bioinformatics methods, aiming to explore the mechanism of IRF4 in DN, and to find potential molecular targets of DN. Methods The GSE142025 dataset was downloaded from the GEO database, including 9 cases in normal control group and 21 cases in advanced DN（aDN） group, and the DEGs were screened. The GSEA enrichment revealed the molecular biological process of the DEGs. Protein-protein interaction networks of DEG were visualized using String and Cytoscape software. The relative expression levels of major DEGs in six DN renal tissues （DN group） and six normal renal tissues after tumor resection （NC group） were verified using RT-qPCR, PAS and SP staining. Results GEO data analysis revealed 1213 differentially-expressed mRNA, of which 684 were up-regulated and 529 were down-regulated. The GSEA and KEGG pathway enrichment of DEGs showed that the DEGs in the DN group were significantly enriched in the JAK/STAT signaling pathway, chemokine signaling pathway, Fcγreceptor-mediated phagocytosis of macrophages signaling pathway, leukocyte transendothelial migration signaling pathway and T cell receptor signaling pathway. The relative expression levels of IRF4, signal lymphocyte activating molecule 6 and IL-2 receptor α subunit mRNA in the DN group were significantly higher compared with those in the NC group （all P < 0.001）. The PAS and SP staining results were consistent with those of RT-qPCR. Conclusion The GSEA enrichment pathways show that the inflammatory pathway is significantly active, and the expression of IRF4 as a hub gene is significantly up-regulated in the DN tissues, which may be involved in the highly-active inflammatory pathway and promote the progression of inflammation in DN.

The directional distance function (DDF) framework has been widely used to estimate the marginal abatement cost (MAC) of CO2 emissions to support decision-making in environmental sustainability and climate change issues. In the use of DDF, an important task is mapping evaluated entities towards a realistic production technology frontier. This study develops a new nonparametric approach for estimating the MAC of CO2 emissions. The approach incorporates the optimal endogenous direction into an enhanced environmental production technology and has three advantages. First, it avoids the arbitrariness in mapping directions. Second, it captures the heterogeneity in optimization paths across different decision-making units (DMUs). Third, it generates more reliable benchmarks for estimating MAC by constructing an environmental technology frontier that is consistent with the material balance principle. We apply the approach to study China's thermal power industry and find clear heterogeneity in MACs and optimization paths at the province level. The results on the optimal endogenous directions show that the DMUs prefer to increase both desirable output and CO2 emissions when CO2 emissions are unregulated. Comparisons with other approaches reveal that arbitrarily mapping exogenous directions and technology representations are likely to generate distorted and unrealistic MACs.