Objective Esophageal cancer (EC) is characterized by a high degree of malignancy and poor prognosis. N6-methyladenosine (m6A), a prominent post-transcriptional modification of mRNA in mammalian cells, plays a pivotal role in regulating various cellular and biological processes. Similarly, cuproptosis has garnered attention for its potential implications in cancer biology. This study seeks to elucidate the impact of m6A- and cuproptosis-related long non-coding RNAs (m6aCRLncs) on the prognosis of patients with EC. Methods The EC transcriptional data and corresponding clinical information were retrieved from The Cancer Genome Atlas (TCGA) database, comprising 11 normal samples and 159 EC samples. Data on 23 m6A regulators and 25 cuproptosis-related genes were sourced from the latest literature. The m6aCRLncs linked to EC were identified through co-expression analysis. Differentially expressed m6aCRLncs associated with EC prognosis were screened using the limma package in R and univariate Cox regression analysis. Subtype clustering was performed to classify EC patients, enabling the investigation of differences in clinical outcomes and immune microenvironment across patient clusters. A risk prognostic model was constructed using least absolute shrinkage and selection operator (LASSO) regression. Its robustness was evaluated through survival analysis, risk stratification curves, and receiver operating characteristic (ROC) curves. Additionally, the model’s applicability across various clinical features and molecular subtypes of EC patients was assessed. To further explore the model’s utility in predicting the immune microenvironment, single-sample gene set enrichment analysis (ssGSEA), immune cell infiltration analysis, and immune checkpoint differential expression analysis were conducted. Drug sensitivity analysis was performed to identify potential therapeutic agents for EC. Finally, the mRNA expression levels of m6aCRLncs in EC cell lines were validated using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results We developed a prognostic risk model based on five m6aCRLncs, namely ELF3-AS1, HNF1A-AS1, LINC00942, LINC01389, and MIR181A2HG, to predict survival outcomes and characterize the immune microenvironment in EC patients. Analysis of molecular subtypes and clinical features revealed significant differences in cluster distribution, disease stage, and N stage between high- and low-risk groups. Immune profiling further identified distinct immune cell populations and functional pathways associated with risk scores, including positive correlations with naive B cells, resting CD4+ T cells, and plasma cells, and negative correlations with macrophages M0 and M1. Additionally, we identified key immune checkpoint-related genes with significant differential expression between risk groups, including TNFRSF14, TNFSF15, TNFRSF18, LGALS9, CD44, HHLA2, and CD40. Furthermore, nine candidate drugs with potential therapeutic efficacy in EC were identified: Bleomycin, Cisplatin, Cyclopamine, PLX4720, Erlotinib, Gefitinib, RO.3306, XMD8.85, and WH.4.023. Finally, RT-qPCR validation of the mRNA expression levels of m6aCRLncs in EC cell lines demonstrated that ELF3-AS1 expression was significantly upregulated in the EC cell lines KYSE-30 and KYSE-180 compared to normal esophageal epithelial cells. Conclusion This study elucidates the role of m6aCRLncs in shaping the prognostic outcomes and immune microenvironment of EC. Furthermore, it identifies potential therapeutic agents with efficacy against EC. These findings hold significant promise for enhancing the survival of EC patients and provide valuable insights to inform clinical decision-making in the management of this disease.
To compare the clinical efficacy of a femoral neck system (FNS) and cannulated screws (CS) in the treatment of femoral neck fracture in young adults.Data from 69 young adults, who were admitted for femoral neck fracture between March 2018 and June 2020, were retrospectively analyzed. Patients were divided into two groups according to surgical method: FNS and CS. The number of intraoperative fluoroscopies, operative duration, length of hospital stay, fracture healing time, Harris score of hip function, excellent and good rate of hip function, and postoperative complications (infection, cut out the internal fixation, nail withdrawal, and femoral neck shortening) were compared between the two groups. Hip joint function was evaluated using the Harris Hip Scoring system.All 69 patients had satisfactory reduction and were followed up for 12-24 months, with a mean follow-up of 16.91 ± 3.01 months. Mean time to fracture healing was13.82 ± 1.59 and 14.03 ± 1.78 weeks in the FNS and CS groups, respectively. There was a statistical difference in the number of intraoperative fluoroscopies between the 2 groups (P = 0.000). There were no significant differences, in operation duration, hospital length of stay, fracture healing time, complications, Harris Hip Score for hip function and excellent and good rate between the two groups (P > 0.05). The incidence of complications was 6.1%(2/33) in the FNS group lower than 25%(9/36) in the CS group, a difference that was statistically significant (P = 0.032). At the last follow-up, the Harris Hip Score of the hip joint in the FNS group was 90.42 ± 4.82and 88.44 ± 5.91 in the CS group.Both treatment methods resulted in higher rates of fracture healing and excellent hip function. Compared with CS, the FNS reduced the number of intraoperative fluoroscopies, radiation exposure to medical staff and patients, and short-term complications including femoral neck shortening and bone nonunion.
The soil quality of the northeast black soil cultivated slopes had been degenerated seriously due to soil erosion.An understanding of the spatial distribution of soil erosion was important for designing conservation programs and deepening the soil erosion rules.In this paper,soil samples were collected on a long and straight cultivated slope which located in keshan county in Helongjiang Province along 4-transects,and the spatial distribution of soil erosion intersity was studied using ~(137)Cs measurement and wavelet analysis.The results showed that there existed a fluctuant period of soil erosion intensity with 142m along 4 transects downslope,which suggested that the downslope intensity of soil transporting alternately changed between weak and strong during the impact of long-term erosive rainfall.Moreover the average erosion rate within the study area was 3054t·km~(-2)·a~(-1),the best fitting result(R~20.96) of the soil erosion rates along the four transects was the sum of sine function.It was further convinced the correctness of the fluctuant of the erosion intensity on the study slope.
Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA.
Several studies have linked gut microbiota to human brain activity. This study used Mendelian randomization (MR) to investigate the causal relationship between gut microbes and delirium.MR was used to select SNPs from large-scale GWAS summary data on 211 gut microbiota taxa and delirium. Inverse variance weighting (IVW), weighted median, and MR-Egger methods were used for statistical analyses. Outliers were assessed using the leave-one-out method. To avoid horizontal pleiotropy, we performed the MR-PRESSO and MR-Egger intercept tests. Cochran's Q and I2 values for IVW and MR-Egger were used to assess heterogeneity.IVW suggested that genetic prediction of the family Desulfovibrionaceae (1.784 (1.267-2.512), P = 0.001), order Desulfovibrionales (1.501 (1.058-2.128), P = 0.023), and genus Candidatus Soleaferrea (1.322 (1.052-1.659), P = 0.016) increased the risk of delirium, but the family Oxalobacteraceae (0.841 (0.722-0.981), P = 0.027), and genera Holdemania (0.766 (0.620-0.946), P = 0.013), Ruminococcus gnavus (0.806 (0.661-0.982), P = 0.033), and Eggerthella (0.815 (0.667-0.997), P = 0.047) reduced the risk of delirium.(1) Limited sample size, (2) inability to assess gut microbiota interactions, and (3) limited to European populations.Our results suggest that presence of the microbial family Desulfovibrionaceae, order Desulfovibrionales, and genus Candidatus Soleaferrea increased the risk of delirium, whereas the Oxalobacteraceae family, and the genera Holdemania, Ruminococcus gnavus, and Eggerthella decreased the risk of delirium. However, the potential of gut probiotic interventions in the prevention of perioperative delirium should be emphasized.
Summary Objective To investigate the genetic level causal association among hyperthyroidism, hypothyroidism, and rheumatoid arthritis (RA). Methods We utilized the genome-wide association studies (GWAS) summary data for exposure (hyperthyroidism and hypothyroidism) and outcome (RA) from the IEU OpenGWAS database. We used two different sets of data (test cohort and validation cohort) for causal assessment of exposure and outcome. To establish a causal relationship between these conditions, we conducted a two-sample Mendelian randomization (MR) analysis. Subsequently, we evaluated the MR analysis results for heterogeneity, horizontal pleiotropy, and outliers, aiming to assess the validity and reliability of the findings. Moreover, we conducted additional analyses to examine the robustness of the MR results, including a “Leave one out” analysis and the MR robust adjusted profile score (MR-RAPS) method, ensuring the robustness and adherence to normal distribution assumptions. Results The findings from the test cohort indicated that hyperthyroidism did not exhibit a genetic causal association with RA ( P = 0.702, odds ratio [OR] 95% confidence interval [CI] = 1.021 [0.918–1.135]). Conversely, hypothyroidism displayed a positive genetic causal relationship with RA ( P < 0.001, OR 95% CI = 1.239 [1.140–1.347]). The analysis results of the validation cohort are consistent with those of the test cohort. Notably, our MR analysis results demonstrated no evidence of heterogeneity, horizontal pleiotropy, or outliers. Furthermore, our MR analysis results remained unaffected by any single nucleotide polymorphism (SNP) and exhibited a normal distribution. Conclusion The results of this study showed that hypothyroidism was positively correlated with RA, while hyperthyroidism was not causally correlated with RA. Hypothyroidism may as a risk factor of RA should be paid attention to in clinical work. Future studies are needed to further confirm this finding.
Changes of the erosion type and the rill erosion process under simple rainfall is one of the key problems in soil erosion research. By placing rare earth elements (REE) on different soil depth across the slope, the simulated rainfall is applied to study the change of erosion type and the rill erosion process. The results indicate that the main erosion type is sheet erosion at the beginning of the experiment, and serious erosion happens after the rill erosion appears. Accumulated the sheet erosion amount and rill erosion increase with the rainfall time, and the increase rate of the latter is bigger than of the former. The ratio of sheet erosion to total erosion decrease and the ratio of rill erosion to total erosion increases with the time passing by. At the end of the experiment, the rill erosion amount reaches 2 to 4 times of the sheet erosion. In this paper, a new REE tracer method is proposed to quantitatively distinguish the sheet erosion amount and the rill erosion amount. Also it can be used to study the process from sheet erosion to rill erosion, and it would be a new method to study the erosion process on slope.
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