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Objective To investigate the short-term outcome and safety of laparoscopic splenectomy combined with peripheral cardia disconnection in treatment of portal hypertension. Methods A retrospective analysis was done with clinical data of 23 patients who underwent laparoscopic splenectomy combined with peripheral cardia disconnection in our hospital from September 2018 to December 2020. Comparison was performed using the clinical data of 13 cases with the method of open surgery, which were comparable to the clinical pathological baseline. Results Less blood loss, longer operative time, and earlier both exhaust time and feeding time were found in the patients of laparoscopic group compared with those in open group. There were no statistically significant differences in postoperative hospital stay and postoperative complications including bleeding, pleural effusion, deep vein thrombosis, gastroparesis, and incision infection between two groups(P>0.05). Conclusions Laparoscopic splenectomy combined with peripheral cardia disconnection can treat portal hypertension which is safe, less blood loss, early postoperative feeding and the short-term outcome similar to open surgery.

Purpose: To explore whether varying degrees of vitreous haemorrhage (VH) and calcification act as risk factors for enucleation in patients with advanced retinoblastoma (RB). Methods: Advanced RB was defined by the international classification of RB (Philadelphia version). Basic information for retinoblastoma patients diagnosed as groups D and E in our hospital between January 2017 and June 2022 was reviewed by logistics regression models. Additionally, a correlation analysis was performed, excluding variables with a VIF (variance inflation factor) >10 from the multivariate analysis. Results: A total of 223 eyes diagnosed with RB were included in assessing VH and calcification; of these, 101 (45.3%) eyes experienced VH, and 182 (76.2%) eyes were found to have calcification within the tumour through computed tomography (CT) or B‐scan ultrasonography. Ninety‐two eyes (41.3%) were enucleated, of which 67 (72.8%) had VH and 68 (73.9%) calcification, both of which were significantly relevant to enucleation (p < 0.001*). Other clinical risk factors, such as corneal edema, anterior chamber haemorrhage, high intraocular pressure during treatment and iris neovascularization, correlated significantly with enucleation (p < 0.001*). Multivariate analysis included IIRC (intraocular international retinoblastoma classification), VH, calcification and high intraocular pressure during treatment as independent risk factors for enucleation. Conclusions: Despite identifying different potential risk factors for RB, there remains significant controversy concerning which patients require enucleation, and the degree of VH varies. Such eyes need to be evaluated carefully, and management with appropriate adjuvant therapy may improve the outcome of these patients. [ABSTRACT FROM AUTHOR]

Albeit N1-Methyladenosine (m1A) RNA modification represents an important regulator of RNA metabolism, the role of m1A modification in carcinogenesis remains enigmatic. Herein, we found that histone lactylation enhances ALKBH3 expression and simultaneously attenuates the formation of tumor-suppressive promyelocytic leukemia protein (PML) condensates by removing the m1A methylation of SP100A, promoting the malignant transformation of cancers. First, ALKBH3 is specifically upregulated in high-risk ocular melanoma due to excessive histone lactylation levels, referring to m1A hypomethylation status. Moreover, the multiomics analysis subsequently identified that SP100A, a core component for PML bodies, serves as a downstream candidate target for ALKBH3. Therapeutically, the silencing of ALKBH3 exhibits efficient therapeutic efficacy in melanoma both in vitro and in vivo, which could be reversed by the depletion of SP100A. Mechanistically, we found that YTHDF1 is responsible for recognition of the m1A methylated SP100A transcript, which increases its RNA stability and translational efficacy. Conclusively, we initially demonstrated that m1A modification is necessary for tumor suppressor gene expression, expanding the current understandings of dynamic m1A function during tumor progression. In addition, our results indicate that lactylation-driven ALKBH3 is essential for the formation of PML nuclear condensates, which bridges our knowledge of m1A modification, metabolic reprogramming, and phase-separation events., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Purpose: Acute retinal arterial ischemia diseases (ARAIDs) are ocular emergencies that require immediate intervention within a restricted therapeutic window to prevent blindness. However, the underlying molecular mechanisms contributing to the pathogenesis of ARAIDs remain enigmatic. Herein, we present the single-cell RNA sequencing (scRNA-seq) alterations during ischemia in the primate retina as a preliminary endeavor in understanding the molecular complexities of ARAIDs., Methods: An ophthalmic artery occlusion model was established through ophthalmic artery ligation in two Macaca fascicularis. scRNA-seq and bioinformatics analyses were used to detect retinal changes during ischemia, which are further validated by immunofluorescence analysis. Western blot and flow cytometry assays were performed to measure the microglia polarization status., Results: The findings of this study reveal notable changes in the retina under acute ischemic conditions. Particularly, retinal ischemia compromised mitochondrial functions of rod photoreceptors, partly leading to the rapid loss of healthy rods. Furthermore, we observed a noteworthy transcriptional alteration in the activation of microglia induced by ischemia. The targeted correction of the proinflammatory cytokine CXCL8 effectively suppresses microglia M1 polarization in retinal ischemia, ultimately reducing the proinflammatory transformation in vitro. In addition, retina ischemia induced the apoptotic inclination of endothelial cells and the heightened interaction with microglia, which signifies the influence of microglia in disrupting the retinal-blood barrier., Conclusions: Our research has successfully identified and described the pathologic alterations occurring in several cell types during a short period of ischemia. These observations provide valuable insights for ameliorating retinal damage and promoting the restoration of vision.

Competing Interests: Declaration of interests The authors declare no competing interests.

Purpose: We aimed to investigate the function of LINC00202 in influencing the malignant progression of gastric cancer (GC)., Methods: The relative level of LINC00202 in GC and adjacent normal tissues was examined by quantitative real-time polymerase chain reaction (qRT-PCR). The difference in LINC00202 level among GC patients with different TNM stages was compared. Subsequently, regulatory effects of LINC00202 on proliferative capacity of AGS and SGC-7901 cells were evaluated. Subcellular distribution of LINC00202 was analyzed. The interaction and correlation between LINC00202 and Krüppel-like factor 2 (KLF2) were analyzed by RNA immunoprecipitation (RIP), Chromatin immunoprecipitation (ChIP) and linear regression test. Finally, the involvement of KLF2 in LINC00202-mediated proliferative ability of GC cells was clarified. LINC00202 was upregulated in GC tissues compared with that in adjacent normal ones. Its level remained higher in GC patients with stage III-IV than those with stage I-II. Silencing LINC00202 markedly attenuated the proliferation of GC cells., Results: LINC00202 was mainly enriched in nucleus. KLF2 level was negatively correlated to and interacted with LINC00202. Transfection of LINC00202 decreased the recruitment ability of EZH2 on KLF2. Importantly, KLF2 partially reversed the regulatory effect of LINC00202 on the proliferative ability of GC cells., Conclusions: LINC00202 enhances the proliferative ability of GC cells via negatively regulating KLF2, thus aggravating the progression of GC.

Background: To identify key microRNAs (miRNAs) and their target mRNAs related to gemcitabine-resistant pancreatic cancer (PC) and investigate the association between gemcitabine-resistant-related miRNAs and mRNAs and immune infiltration., Methods: Expression profiles of miRNAs and mRNAs were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed miRNAs and mRNAs (referred to as "DEmiRNAs" and "DEmRNAs", respectively) were distinguished between gemcitabine-resistant PC cells and its parental cells. The DEmRNAs targeted by the DEmiRNAs were retrieved using miRDB, microT, and Targetscan. Furthermore, GO and KEGG pathway enrichment analysis and GSEA were performed. The Kaplan-Meier plotter was used to analyze the prognosis of key DEmiRNAs and DEmRNAs on PC patients. The relationship between the key DEmRNAs and tumor-infiltrating immune cells in PC was investigated using CIBERSORT method using the LM22 signature as reference. Key infiltrating immune cells were further analyzed for the associations with prognosis of TCGA PAAD patients., Results: Four DEmiRNAs, including hsa-miR-3178, hsa-miR-485-3p, hsa-miR-574-5p, and hsa-miR-584-5p, were identified to target seven DEmRNAs, including MSI2, TEAD1, GNPDA1, RND3, PRKACB, TRIM68, and YKT6, individually, in gemcitabine-resistant PC cells versus parental cells. Gemcitabine-resistant PC cells were enriched in proteasome-related, immune-related, and memory CD4 + T cell-related pathways, indicating a gemcitabine therapeutic effect on PC cells. All four DEmiRNAs and almost all DEmRNAs had an impact on the prognosis of PC patients. All seven DEmRNAs had remarkable effects on CD4 + memory T cells, which were affected by the gemcitabine therapeutic effect. Effector memory CD4 + T cells rather than central memory CD4 + T cells predicted a good prognosis according to the TCGA PAAD dataset., Conclusions: Gemcitabine resistance can alter the fraction of memory CD4 + T cells via hsa-miR-3178, hsa-miR-485-3p, hsa-miR-574-5p and hsa-miR-584-5p targeted MSI2, TEAD1, GNPDA1, RND3, PRKACB, TRIM68, and YKT6 network in PC., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)