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Background: Liver ischemia–reperfusion injury (LIRI) is closely associated with immune infiltration, which commonly occurs after liver surgery, especially liver transplantation. Therefore, it is crucial to identify the genes responsible for LIRI and develop effective therapeutic strategies that target immune response. Methylation modifications in mRNA play various crucial roles in different diseases. This study aimed to identify potential methylation-related markers in patients with LIRI and evaluate the corresponding immune infiltration. Methods: Two Gene Expression Omnibus datasets containing human liver transplantation data (GSE12720 and GSE151648) were downloaded for integrated analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted to investigate the functional enrichment of differentially expressed genes (DEGs). Differentially expressed methylation-related genes (DEMRGs) were identified by overlapping DEG sets and 65 genes related to N6-methyladenosine (m6A), 7-methylguanine (m7G), 5-methylcytosine (m5C), and N1-methyladenosine (m1A). To evaluate the relationship between DEMRGs, a protein–protein interaction (PPI) network was utilized. The core DEMRGs were screened using three machine learning algorithms: least absolute shrinkage and selection operator, random forest, and support vector machine-recursive feature elimination. After verifying the diagnostic efficacy using the receiver operating characteristic curve, we validated the expression of the core DEMRGs in clinical samples and performed relative cell biology experiments. Additionally, the immune status of LIRI was comprehensively assessed using the single sample gene set enrichment analysis algorithm. The upstream microRNA and transcription factors of the core DEMRGs were also predicted. Results: In total, 2165 upregulated and 3191 downregulated DEGs were identified, mainly enriched in LIRI-related pathways. The intersection of DEGs and methylation-related genes yielded 28 DEMRGs, showing high interaction in the PPI network. Additionally, the core DEMRGs YTHDC1, METTL3, WTAP, and NUDT3 demonstrated satisfactory diagnostic efficacy and significant differential expression and corresponding function based on cell biology experiments. Furthermore, immune infiltration analyses indicated that several immune cells correlated with all core DEMRGs in the LIRI process to varying extents. Conclusions: We identified core DEMRGs (YTHDC1, METTL3, WTAP, and NUDT3) associated with immune infiltration in LIRI through bioinformatics and validated them experimentally. This study may provide potential methylation-related gene targets for LIRI immunotherapy. [ABSTRACT FROM AUTHOR]

Background: The objective of the study is to determine the safety and efficiency of the modified laparoscopic percutaneous extraperitoneal closure (LPEC) to treat pediatric patients with inguinal hernia or hydrocele. Methods: From January 2014 to July 2018, the patients with inguinal hernia or hydrocele who were operated on using modified LPEC were included. We modified LPEC with a sledge-shaped needle and reinforcement flag. By means of medial umbilical fold, the reinforcement surgery should be performed on the patients with huge internal rings (diameter >1.5 cm). Operative time, complication rate, incidence of reinforcement, and contralateral patent processus vaginalis were described between inguinal hernia and hydrocele. Results: In this study, 764 patients with inguinal hernia and 435 patients with hydrocele were successfully performed by the modified LPEC. The 383 (50.1%) patients with inguinal hernia and 266 (61.1%) patients with hydrocele were identified with a contralateral patency of internal ring and underwent simultaneous prophylactic surgery. During surgical procedures, the medial umbilical fold reinforcement (inguinal hernia/hydrocele = 50/1) was performed on 51 patients. Hernia recurrence occurred in 2 cases. All patients had a good cosmetic appearance without additional dissection. Conclusion: Modified LPEC using a sledge-shaped needle and applying the medial umbilical fold reinforcement is a safe and effective surgical procedure. [ABSTRACT FROM AUTHOR]

Mannose-binding lectin-associated serine protease 1 (MASP1) plays a crucial role in the complement lectin pathway and the mediation of immune responses. However, comprehensive research on MASP1 across various cancer types has not been performed to date. This study aimed to evaluate the significance of MASP1 in pan-cancer. The Cancer Genome Atlas (TCGA), UCSC Xena and Genotype Tissue Expression (GTEx) databases were used to evaluate the expression profiles, genomic features, prognostic relevance, and immune microenvironment associations of MASP1 across 33 cancer types. We observed significant dysregulation of MASP1 expression in multiple cancers, with strong associations between MASP1 expression levels and diagnostic value as well as patient prognosis. Mechanistic insights revealed significant correlations between MASP1 levels and various immunological and genomic factors, including tumor-infiltrating immune cells (TIICs), immune-related genes, mismatch repair (MMR), tumor mutation burden (TMB), and microsatellite instability (MSI), highlighting a critical regulatory function of MASP1 within the tumor immune microenvironment (TIME). In vitro and in vivo experiments demonstrated that MASP1 expression was markedly decreased in liver hepatocellular carcinoma (LIHC). Moreover, the overexpression of MASP1 in hepatocellular carcinoma (HCC) cell lines significantly inhibited their proliferation, invasion and migration. In conclusion, MASP1 exhibits differential expression in the pan-cancer analyses and might play an important role in TIME. MASP1 is a promising prognostic biomarker and a potential target for immunological research, particularly in LIHC., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yong Ma reports financial support was provided by the National Natural Scientific Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

N6-Methyladenosine (m 6 A) plays key roles in the regulation of biological functions and cellular mechanisms for ischaemia reperfusion (IR) injury in different organs. However, little is known about the underlying mechanisms of m 6 A-modified mRNAs in hepatic IR injury. In mouse models, liver samples were subjected to methylated RNA immunoprecipitation with high-throughput sequencing (MeRIP-seq) and RNA sequencing (RNA-seq). In total, 16917 m 6 A peaks associated with 4098 genes were detected in the sham group, whereas 21,557 m 6 A peaks associated with 5322 genes were detected in the IR group. There were 909 differentially expressed m 6 A peaks, 863 differentially methylated transcripts and 516 differentially m 6 A modification genes determined in both groups. The distribution of m 6 A peaks was especially enriched in the coding sequence and 3'UTR. Furthermore, we identified a relationship between differentially m 6 A methylated genes (fold change≥1.5/≤ 0.667, p value≤0.05) and differentially expressed genes (fold change≥1.5 and p value≤0.05) to obtain three overlapping predicted target genes (Fnip2, Phldb2, and Pcf11). Our study revealed a transcriptome-wide map of m 6 A mRNAs in hepatic IR injury and might provide a theoretical basis for future research in terms of molecular mechanisms.