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Histone modification is an important form of epigenetic regulation. Thereinto, histone methylation is a critical determination of chromatin states, participating in multiple cellular processes. As a conserved histone methylation mark, histone 3 lysine 36 trimethylation (H3K36me3) can mediate multiple transcriptional-related events, such as the regulation of transcriptional activity, transcription elongation, pre-mRNA alternative splicing, and RNA m6A methylation. Additionally, H3K36me3 also contributes to DNA damage repair. Given the crucial function of H3K36me3 in genome regulation, the roles of H3K36me3 and its sole methyltransferase SETD2 in pathogenesis, especially malignancies, have been emphasized in many studies, and it is conceivable that disruption of histone methylation regulatory network composed of "writer", "eraser", "reader", and the mutation of H3K36me3 codes have the capacity of powerfully modulating cancer initiation and development. Here we review H3K36me3-mediated biological processes and summarize the latest findings regarding its role in cancers. We highlight the significance of epigenetic combination therapies in cancers. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to identify the risk factors for postoperative delirium (POD) in elderly patients undergoing heart valve surgery with cardiopulmonary bypass (CPB). Methods: Elderly patients undergoing elective heart valve surgery with CPB in The First Affiliated Hospital of Wenzhou Medical University between March 2022 and March 2023 were selected for this investigation. They were divided into a POD group and a non-POD group. Their baseline information was collected and recorded, and the patients were subjected to neurocognitive function assessment using the Mini-Mental State Examination and the Montreal Cognitive Assessment scales before surgery. We also recorded their intraoperative indicators such as duration of surgery, duration of CPB, duration of aortic cross-clamp, blood transfusion, and postoperative indicators such as duration of mechanical ventilation, postoperative 24-hour drainage volume, and pain score. Regional cerebral oxygen saturation was monitored intraoperatively by near-infrared spectroscopy based INVOS5100C Regional Oximeter. Patients were assessed for the occurrence of POD using Confusion Assessment Method for the Intensive Care Unit, and logistic regression analysis of risk factors for POD was performed. Results: The study finally included 132 patients, with 47 patients in the POD group and 85 ones in the non-POD group. There were no significant differences in baseline information and preoperative indicators between the two groups. However, marked differences were identified in duration of surgery, duration of CPB, duration of aortic cross-clamp, duration of postoperative mechanical ventilation, postoperative length of stay in cardiac intensive care unit, postoperative length of hospital stay, intraoperative blood transfusion, postoperative pain score, and postoperative 24-hour drainage volume between the two groups (p < 0.05). Additionally, the two groups had significant differences in rScO2 at each intraoperative time point and in the difference of rScO2 from baseline at each intraoperative time point (p < 0.05). Multivariate logistic regression analysis showed that duration of surgery > 285 min (OR, 1.021 [95% CI, 1.008–1.035]; p = 0.002), duration of postoperative mechanical ventilation > 23.5 h (OR, 6.210 [95% CI, 1.619–23.815]; p = 0.008), and postoperative CCU stay > 3.5 d (OR, 3.927 [95% CI, 1.046–14.735]; p = 0.043) were independent risk factors of the occurrence of POD while change of rScO2 at T1>50.5 (OR, 0.832 [95% CI 0.736–0.941]; p = 0.003) was a protective factor for POD. Conclusion: Duration of surgery duration of postoperative mechanical ventilation and postoperative CCU stay are risk factors for POD while change of rScO2 at T1 is a protective factor for POD in elderly patients undergoing heart valve surgery with CPB. [ABSTRACT FROM AUTHOR]

Backgroud: The role of epigenetic modifications in tumorigenesis has been widely reported. However, the role and mechanism of H3K4me3 modification in lung adenocarcinoma (LUAD) are rarely reported systematically. We, therefore, sought to analyze the characteristics of LUAD associated with H3K4me3 modification, build an H3K4me3-lncRNAs score model to predict the prognosis of patients with LUAD and clarify the potential value of H3K4me3 in immunotherapy of LUAD. Methods: We evaluated H3K4me3-lncRNA patterns and H3K4me3-lncRNA scores of 477 LUAD samples based on 53 lncRNAs closely correlated to H3K4me3 regulators and comprehensive analyzed the role of these patterns in tumorigenesis and tumor immunity. Using Gene set variation analysis (GSVA), we systematically evaluated the H3K4me3 level of every sample and deeply analyzed the effect of H3K4me3 on the prognosis of LUAD. In addition, we included two independent immunotherapy cohorts to study the impact of high H3K4me3 score on the prognosis of patients. We also used an independent cohort with 52 matched paraffin specimens of LUAD to verify the impact of high H3K3me3 expression on the prognosis of patients. Results: We identified three H3K4me3-lncRNA patterns that exhibited specific immune characteristics. Characterized by immunosuppressive and increased TGFβ-mediated epithelial-mesenchymal transition (EMT), patients with high H3K4me3-lncRNA score had a poor overall survival and decreased H3K4me3 score. H3K4me3 score was significantly positively correlated with CD4+T-cell and CD8+T-cell activation, programmed cell death and immune checkpoints (ICs) expression, and was negatively correlated with MYC pathway, TP53 pathway, and cell proliferation. Patients with high H3K4me3 score showed elevated expression of ICs, potentiated CD4 T-cell and CD8 T-cell activation, increased programmed cell death, and suppressed cell proliferation and TGFβ-mediated EMT. Patients with high H3K4me3 score and high expression of CTLA4, ICOS, TIGIT, PDCD1LG2, IDO1, CD274, PDCD1, LAG3, or HAVCR2 had the best survival advantage. Two independent immunotherapy cohorts verified that patients with high H3K4me3 score showed an increased inflamed tumor microenvironment (TME) phenotype and enhanced anti-PD-1/L1 immunotherapy response. Immunohistochemistry (IHC) data from 52 matched paraffin specimens of LUAD confirmed that the protein level of H3K4me3 in tumor was significantly lower than that of paracancerous tissues and H3K4me3 brought significant survival benefits to patients with LUAD. Conclusions: We build an H3K4me3-lncRNAs score model to predict the prognosis of patients with LUAD. More importantly, this study revealed characteristics of H3K4me3 modification in LUAD and clarified the important potential role of H3K4me3 on tumor immunotherapy and patients' survival. [ABSTRACT FROM AUTHOR]

Background: The Asia lotus (Nelumbo nucifera Gaertn.) is an ornamental aquatic plant with high economic value. Flower colour is an important ornamental trait, with much of N. nucifera breeding focusing on its yellow flowers. To explore the yellow flower colouration mechanism in N. nucifera, we analysed its pigment constituents and content, as well as gene expression in the flavonoid pathway, in two N. nucifera cultivars. Results: We performed metabolomic and gene expression analyses in two N. nucifera cultivars with yellow and white flowers, Molinqiuse (MLQS) and Yeguangbei (YGB), respectively, at five stages of flower colouration. Based on phenotypic observation and metabolite analyses, the later stages of flower colouration (S3–S5) were determined to be key periods for differences between MLQS and YGB, with dihydroflavonols and flavonols differing significantly between cultivars. Dihydroquercetin, dihydrokaempferol, and isorhamnetin were significantly higher in MLQS than in YGB, whereas kaempferol was significantly higher in YGB. Most of the key homologous structural genes in the flavonoid pathway were significantly more active in MLQS than in YGB at stages S1–S4. Conclusion: In this study, we performed the first analyses of primary and secondary N. nucifera metabolites during flower colouration, and found that isorhamnetin and kaempferol shunting resulted in petal colour differences between MLQS and YGB. Based on our data integration analyses of key enzyme expression in the putative flavonoid pathways of the two N. nucifera cultivars, NnFLS gene substrate specificity and differential expression of NnOMTs may be related to petal colour differences between MLQS and YGB. These results will contribute to determining the mechanism of yellow flower colouration in N. nucifera, and will improve yellow petal colour breeding in lotus species. [ABSTRACT FROM AUTHOR]

Background: Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is an uncommon primary liver malignancy and little known about the clinical and imaging characteristics of cHCC-CC. We aim to define the demographics, imaging features of cHCC-CC on contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CT) in this study.Methods: From January 2005 to December 2014, 45 patients with pathologically proven cHCC-CC who underwent preoperative CEUS and 43 patients who had additional CT scan in our institution were included. A retrospective review of the imaging studies and clinical data in these patients was conducted.Results: In our series, cHCC-CC accounted for 1.6 % of all primary liver malignancy. Mean age of patient with cHCC-CC was 52.8 year (range: 28-74 year) and 88.9 % (40/45) of patients were male. Thirty of forty five patients (66.7 %) had cirrhosis and 20 % (9/45) of patients had chronic hepatitis B without cirrhosis. Alpha--fetoprotein (AFP) was elevated in 62.2 % (28/45) of patients and carbohydrate antigen 19-9 (CA19-9) elevated in 22.2 % (10/45) of patients). Both AFP and CA19-9 were simultaneously elevated in 15.6 % (7/45) of patients. Enhancement pattern resembling cholangiocarcinoma (CC) was noted in 53.3 % (24/45) of patients (on CEUS and in 30.2 % (13/43) of patients at CT. Enhancement pattern resembling hepatocellular carcinoma (HCC) was observed in 42.2 % (19/45) of patients on CEUS and in 58.1 % (25/43) of patients at CT. The percentage of tumors showing CC enhancement pattern (27.9 %, 12/43) was comparable with that of tumors showing HCC enhancement pattern (44.2 %, 19/43) on both CEUS and CT (p = 0.116). Simultaneous elevation of tumor markers (AFP and CA19-9) or tumor marker elevation (AFP or CA19-9) in discordance with enhancement pattern on CEUS was demonstrated in 51.1 % (23/45) of patients and on CT in 53.5 % (23/43) of patients, which was significantly more than simultaneous elevation of tumor markers (AFP and CA19-9) alone (p = 0.000).Conclusions: The clinical characteristics of cHCC-CC are similar to those of HCC. The cHCC-CC tumors display enhancement patterns resembling CC or HCC in comparable proportion on both CEUS and CT. Combination of simultaneous elevation of tumor makers (AFP and CA19-9) and tumor mark elevation (AFP or CA19-9) in discordance with presumptive imaging findings on CEUS or CT may lead significantly more patients to be suspicious of the diagnosis of cHCC-CC. [ABSTRACT FROM AUTHOR]

Background: PolyC-RNA-binding protein 1 (PCBP1) functions as a tumour suppressor and RNA regulator that is downregulated in human cancers. Here, we aimed to reveal the biological function of PCBP1 in lung adenocarcinoma (LUAD).Methods: First, PCBP1 was identified as an important biomarker that maintains LUAD through The Cancer Genome Atlas (TCGA) project screening and confirmed by immunohistochemistry and qPCR. Via colony formation, CCK8, IncuCyte cell proliferation, wound healing and Transwell assays, we confirmed that PCBP1 was closely related to the proliferation and migration of LUAD cells. The downstream gene DKK1 was discovered by RNA sequencing of PCBP1 knockdown cells. The underlying mechanisms were further investigated using western blot, qPCR, RIP, RNA pulldown and mRNA stability assays.Results: We demonstrate that PCBP1 is downregulated in LUAD tumour tissues. The reduction in PCBP1 promotes the proliferation, migration and invasion of LUAD in vitro and in vivo. Mechanistically, the RNA-binding protein PCBP1 represses LUAD by stabilizing DKK1 mRNA. Subsequently, decreased expression of the DKK1 protein relieves the inhibitory effect on the Wnt/β-catenin signalling pathway. Taken together, these results show that PCBP1 acts as a tumour suppressor gene, inhibiting the tumorigenesis of LUAD.Conclusions: We found that PCBP1 inhibits LUAD development by upregulating DKK1 to inactivate the Wnt/β-catenin pathway. Our findings highlight the potential of PCBP1 as a promising therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Extranodal follicular dendritic cell sarcoma (FDCS) is a very rare malignancy with a variable clinical course. It is often not considered and has the potential to result in a misdiagnosis of other common sarcomas or sarcomatoid carcinomas. This is particularly true with the preoperative biopsy specimen, in which the tissue sample is often small. Case presentation: A case of FDCS in a 63-year-old woman, arising in the urinary bladder, a previously unreported site, is described. The patient presented with the typical clinical symptoms of a bladder cancer and the morphology of the tumor was similar to a lymphoepithelioma-like carcinoma, ultimately resulting in it being misdiagnosed. The patient received radical cystectomy, without further radiotherapy or chemotherapy. Two years after operation, a metastatic tumor to the lung was found. The mass of the right main bronchus lumen was frozen and resected through bronchoscopy and radiotherapy was performed. The patient has lived with the tumor since then. Conclusions: This paper presents the first FDCS occurring in the urinary bladder with metastasis to the lung and emphasizes potential diagnostic pitfalls. [ABSTRACT FROM AUTHOR]

Background: Ischemic Moyamoya disease is one of the important causes of stroke, which leads to severe impairment in cognitive functions. This cognitive impairment occurs prior to stroke. However, the cognitive functions that are impaired and the mechanisms of these impairments have not been determined.Methods: We analyzed 12 patients with Moyamoya disease and 12 controls. All participants underwent cognitive tests and magnetic resonance imaging (MRI) scans. The diffusion tensor imaging (DTI) data was processed using Tract-Based Spatial Statistics (TBSS). Significantly different white matter areas were correlated with different cognitive functions.Results: There were significant differences in intelligence and subtraction between the patients and controls (p < 0.05). The parameters of DTI such as fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) have different changes in anterior thalamic radiation, inferior fronto-occipital fasciculus (IFO), superior longitudinal fasciculus (SLF), uncinate fasciculus (UF), inferior longitudinal fasciculus, forceps minor, and other regions between the two groups.Conclusion: Left UF and IFO may be the key brain regions affecting arithmetic function, while bilateral IFO has an effect on intelligence. RD and AD may be better indicators for early prediction of chronic white matter damage than FA, while MD tends to have a comprehensive indirect change. There is cognitive impairment in ischemic MMD, which is closely related to white matter impairment.Trial Registration: Clinical Trial Registration, Unique identifier: ChiCTR1900023610 . Registered 4 June 2019 - Prospective study registered. [ABSTRACT FROM AUTHOR]

Background: Mediastinal follicular dendritic cell sarcoma (FDCS) is extremely rare. Due to potential under-recognization of this disease, it happens to be misdiagnosed, especially on core needle biopsy. We report 3 cases of mediastinal FDCS and provide a literature review to improve better understanding of the tumor and to reduce misdiagnosis. Methods: Three cases of mediastinal FDCS in our clinic practice were studied, including their core needle biopsy and resected specimens, and those cases reported previously in English literature were retrieved and analyzed. Results: The core needle biopsy of case 1 showed a tumor reminiscent of classical Hodgkin's lymphoma (CHL), while the resected mass was finally diagnosed with FDCS combined with hyaline-vascular Castleman's disease. Both the biopsy and resected tissue of case 2 were constitutive of the clear epithelioid cells with marked atypia. In both cases, definitive diagnoses were not made on core needle biopsy. In case 3, there were some areas morphologically similar to CHL, and some areas contained ovoid to spindle-shaped tumor cells with fascicular pattern. The analysis of 43 cases of mediastinal FDCS showed the age of patients were from 16 to 76 years old, the male to female ratio was 1.5:1, the maximal tumor diameters were 3–17 cm. 18 cases were underwent preoperative biopsy, whereas 15 (83.3%) of which were misdiagnosed initially, often as lymphoma. 32 patients had available follow-up data, the rates of recurrence, metastasis, and mortality were 12.5, 18.8 and 28.1%, respectively. Current limited data suggested no statistical differences between adverse prognosis and gender, age, tumor size, necrosis, or different therapeutics, respectively. Conclusions: Mediastinal FDCS is a rare malignancy that has yet not been fully understood and been often misdiagnosed, particularly when making a diagnosis on core needle biopsy. Increased awareness of this enigmatic tumor is crucial to avoid diagnostic pitfalls. [ABSTRACT FROM AUTHOR]