Background Lung cancer is a malignant tumor with the highest mortality worldwide. Abnormalities in the ubiquitin proteasome system are considered to be contributed to lung cancer progression with deleterious effects. DDB1 and CUL4 associated factor 13 (DCAF13) is a substrate receptor of the E3 ubiquitin ligase CRL4, but its role in lung cancer remains unknown. In this study, we aimed to investigate the regulatory mechanisms of DCAF13 in lung adenocarcinoma (LUAD). Methods So as to investigate the effect of DCAF13 on lung adenocarcinoma cell function using in vivo and in vitro. Mechanistically, we have identified the downstream targets of DCAF13 by using RNA-sequencing, as well as ubiquitination assays, co-immunoprecipitation, immunofluorescence, immunohistochemistry and chromatin immunoprecipitation - qPCR experiments. Results Our findings reveal that DCAF13 is a carcinogenic factor in LUAD, as it is highly expressed and negatively correlated with clinical outcomes in LUAD patients. Through RNA-sequencing, it has been shown that DCAF13 negatively regulates the p53 signaling pathway and inhibits p53 downstream targets including p21, BAX, FAS, and PIDD1. We also demonstrate that DCAF13 can bind to p53 protein, leading to K48-linked ubiquitination and degradation of p53. Functionally, we have shown that DCAF13 knockdown inhibits cell proliferation and migration. Our results highlight the significant role of DCAF13 in promoting LUAD progression by inhibiting p53 protein stabilization and the p53 signaling pathway. Furthermore, our findings suggest that high DCAF13 expression is a poor prognostic indicator in LUAD, and DCAF13 may be a potential therapeutic target for treating with this aggressive cancer. Conclusions The DCAF13 as a novel negative regulator of p53 to promote LUAD progression via facilitating p53 ubiquitination and degradation, suggesting that DCAF13 might be a novel biomarker and therapeutical target for LUAD.

Objective This study aims to examine the impact of preoperative fibrinogen concentration on the short-term outcomes and hospital length of stay (LOS) of patients undergoing Coronary Artery Bypass Grafting (CABG). Methods Between January 2010 and June 2022, a retrospective analysis comprised 633 patients who sequentially received isolated, primary CABG. These patients were categorized into normal fibrinogen group (fibrinogen < 3.5 g/L) and high fibrinogen group (fibrinogen ≥ 3.5 g/L) according to preoperative fibrinogen concentration. The primary outcome was LOS. To correct for confounding and investigate the effect of preoperative fibrinogen concentration on the short-term outcomes and LOS, we employed propensity score matching (PSM). The correlation between fibriongen concentration and LOS in subgroups was examined using subgroup analysis. Results We categorized 344 and 289 patients in the “normal fibrinogen group” and “high fibrinogen group”, respectively. After PSM, compared to the normal fibrinogen group, the high fibrinogen group had a longer LOS [12.00 (9.00–15.00) vs. 13.00 (10.00–16.00), P = 0.028] and higher incidence of postoperative renal impairment [49 (22.1%) vs. 72 (32.4%), P = 0.014]. Cardiopulmonary bypass (CPB) or non-CPB CABG patients showed similar correlations between various fibrinogen concentrations and LOS, according to subgroup analyses. Conclusions Fibrinogen is an independent preoperative predictor of both the LOS and the postoperative renal impairment that occurs after CABG. Patients with high preoperative fibrinogen concentration had a higher incidence of postoperative renal impairment and a longer LOS, emphasizing the significance of preoperative fibrinogen management.

To explore the effect and mechanism of autologous blood transfusion impeding glycolysis in macrophages and inhibiting red blood cells (RBCs) injury in type 2 diabetes through PI3K/Akt/PKM2 signaling axis. Cell transfection were performed and diabetic mice model was constructed. The group were divided into control (NC) and type 2 diabetes model (T2D). T2D model mice were injected with preserved autologous blood, si-PI3K, si-PKM2, si-NC Tran+T2D, (Tran+T2D+si-PI3K, Tran+T2D si-PKM2, Tran+T2D+si-NC) through tail vein. The anti-oxidative effects of transfusion of autologous blood in CD14+ monocytes were detected. The expression of PI3K/Akt/PKM2 protein in CD14+ monocytes were examined by western blot. Effect of autologous blood transfusion ameliorating RBCs injury by regulating PI3K and PKM2 in T2D mice were detected. Effects on oxidative stress in T2D mice were all overturned after autologous blood transfusion in T2D mice. The results manifested that the levels of PI3K, pAkt and PKM2 were downregulated, while the expression of HIF-1α was upregulated in CD14+ monocytes from T2D mice, whereas these influences were all effectively reversed by autologous blood transfusion in T2D mice. The survival rate of RBCs in the serum of T2D mice was declined in the serum of T2D mice, while the effect was reversed by the autologous blood transfusion. Autologous blood transfusion can reduce glycolysis in macrophages and inhibit the release of inflammatory factors through the PI3K/PKM2 signal axis, thereby inhibiting red blood cell damage and improving the oxygen-carrying capacity and survival activity of RBCs in diabetic patients.

Autologous blood transfusion is an important blood protection measure. Red blood cells have a certain degree of immunogenicity and their surface membrane proteins CD28 and MHC can participate in the immune response and interact with CD8+ T cells. We build a cell model with a transwell system. The binding characteristics of RBCs and CD8+ T cells were observed with a fluorescent confocal microscope. The content of the inflammatory factor TNF-α and IFN-γ produced was analyzed by ELISA. The proliferation characteristics of CD8+ T cells were analyzed by CFSE staining, and the content of CD3+CD8+ T cells was analyzed by flow cytometry. Cell migration and invasion experiments were used to analyze the malignant metastasis ability of liver cancer cells. The expression of vimentin, E-cadherin, and β-catenin was analyzed by Western blot. We establish a liver cancer model in rats and group them for autologous blood transfusion. The content of CD3+CD8+T cells in the blood of each group of rats was analyzed by flow cytometry. Western blot was used to analyze the expression of vimentin, E-cadherin, and β-catenin in the liver tissues of rats in each group. The red blood cells in the autologous reinfusion blood and CD8+ T cells have an obvious combination. The degree of combination of the two is related to the expression of CD28 and MHC. If CD28 and MHC are expressed at the same time, the combination of the two cells will be high, the proliferation of CD8+ T cells will increase, and the expression of inflammatory factors will also increase, while the expression of the three proteins that are positively correlated with the activity of cancer cells will decrease. If only one of CD28 and MHC is normally expressed, the result is contrary to the situation where both membrane proteins are normally expressed. Our project has proved that autologous infusion of red blood cell surface membrane proteins CD28 and MHC combined with CD8+ T cells can promote the proliferation of CD8+ T cells to inhibit the malignant transformation of liver cancer.

Abstract Background Sepsis patients have the worst outcomes when affected by coronavirus disease 2019 (COVID-19). Unknown are the molecular mechanisms underlying the relationship between sepsis and COVID-19. The primary purpose of the present work was to establish whether there is interaction between COVID-19 and sepsis in terms of molecular perturbation and to uncover a molecular signature, molecular networks, and signaling pathways shared by the two disorders. Methods We retrieved the sepsis and COVID-19 datasets from the Gene Expression Omnibus (GEO) database and used Weighted Gene Co-Expression Network Analysis (WGCNA) to identify key modules. On the common genes residing in the sepsis and COVID-19 associated modules, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Then, using the STRING database, we constructed the protein-protein interaction (PPI) network and identified its hub genes. Finally, The immune cell infiltration score and immune-associated pathway activity were calculated using single-sample gene set enrichment analysis (ssGSEA). Results Functional enrichment analysis indicated that antigen processing and presentation of peptide antigen via MHC class I, antigen processing and presentation of peptide antigen, antigen processing and presentation, T cell mediated cytotoxicity and T cell mediated immunity were probably involved in sepsis comorbided with COVID-19. Pathway enrichment analysis of the common genes of key modules identified the underlying biological processes in COVID-19-related sepsis, including Antigen processing and presentation, Phagosome, Natural killer cell mediated cytotoxicity and Adipocytokine signaling pathway. PPI network construction indicated that sepsis comorbided with COVID-19 is likely related to 5 hub genes, including B2M, TNFSF10, TLR3, JAK2, and IRF2. ssGSEA results illustrated that 5 hub genes are closely related to the immune status of sepsis. Conclusions In summary, our work indicated a total of 5 hub genes including B2M, TNFSF10, TLR3, JAK2, and IRF2, which especially underlie the comorbidity mechanisms of sepsis and COVID-19. These shared pathways may give new targets for mechanistic research into the development and management of sepsis and COVID-19.

IntroductionLiver cancer is a common tumor of digestive system. Hepatectomy sometimes results in massive hemorrhage, and intraoperative autotransfusion is often required.Material and methodsMethods: In this basic research, the liver cancer rat model was established, and the visible liver cancer tissue was surgically removed, and the blood of the mice was recovered.ResultsThe results showed that the model group had the highest recurrence and metastasis of liver cancer, and the lowest was autotransfusion group. Flow cytometry showed that the number of HLA-DQB1 positive cells, the content of CD4+CD25+T cells, and the proliferation of CD4+T cells were the most in the autotransfusion group, followed by the model group, and the least in the auto+HLA-DQB1 group, which showed no difference from the control group. Immunohistochemistry and western blot analysis showed that the lowest expression of PDCD1 protein was in the autotransfusion group, which showed no significant difference from the control group, and the highest expression was in auto-HLA-DQB1, followed by the model group.ConclusionsIt elucidates the molecular mechanism that autotransfusion will activate the up-regulated expression of signal molecule HLA-DQB1, enhance the immune surveillance of CD4+T cells, reduce the expression of PDCD1 on the surface molecule of liver cancer cells, and inhibit liver cancer metastasis.Autotransfusion activated the expression of signaling molecule HLA-DQB1, enhanced the immune surveillance of CD4+T cells, reduced the expression of PDCD1 on the surface of liver cancer cells, and reduced the metastasis and recurrence of liver cancer.

Introduction Systemic inflammatory and immune suppressive incidents constitute a significant hallmark of red blood cell transfusion's adverse effects. These adverse side effects are seemingly associated with old blood transfusion; therefore, we aim to investigate the underlying mechanism of fresh autologous blood transfusion (fABT) and its subsequent effect in diabetic mice. Material and methods In the present study, we utilized 60 Swiss male mice aged 6-8 weeks, categorized into normal, diabetic, and freshly transfused with autologous blood. After treating the mice accordingly, further experimentations took place as we assessed the M1/M2 macrophage polarization concerning CD16/CD32/CD206 cells by flow cytometry, determined the mitochondrial metabolism using Lowry's analysis, measured hepatic oxidative stress using MDA and SOD assays, and examined the erythrocytic oxygen-carrying capacity (Q value) and oxygen consumption rate (OCR) and osmotic fragility. Results Results showed that fresh autologous blood transfusion markedly reduced M2 macrophage polarization, enhanced hepatic mitochondrial metabolism, reduced hepatic oxidative stress, and promoted red blood cells' oxygen-carrying capacity while reducing its osmotic fragility and oxygen consumption. Moreover, we found that fABT promoted the IGF2/PI3K signaling pathway, These results indicate the vital necessity of providing fresh autologous blood transfusion during therapy or surgeries. Conclusions In conclusion, our results are the first to highlight the underlying mechanism in which how fABT modulates physiological patterns in diabetic animals model, proposing a sound basis for utilizing fABT in clinical applications.

OBJECTIVES:Chronic obstructive pulmonary disease (COPD) patients have higher laryngopharyngeal reflux (LPR)-related symptom incidence. But LPR treatment is empirical. We aimed to determine the frequency of LPR, diagnosed by 24-hour Dx-pH monitoring, among acute exacerbations of COPD (AECOPD) patients with Reflux Symptom Index (RSI) ≥13 and investigate proton pump inhibitor (PPI) treatment effect on LPR, COPD symptoms, and pulmonary function.METHODS:From January 2016 to September 2017, 102 AECOPD patients with RSI ≥13 were enrolled. COPD assessment test (CAT), mMRC dyspnea scale, pulmonary function tests, and 24-hour Dx-pH monitoring were performed. The Ryan score was evaluated by using the Dx-pH DataView Lite software, which identifies patients with abnormal pharyngeal pH environments. Associations among RSI, pulmonary function test results, and Ryan score parameters were evaluated. The abovementioned assessments were reperformed after treatment, and pre- and posttreatment data were compared.RESULTS:Of the 102 eligible patients, 49 (48.04%) were diagnosed with LPR based on Ryan score. Percentage of the forced expiratory volume at 1 second (FEV1%) was significantly worse in Ryan-positive than in Ryan-negative AECOPD patients. There were significant negative correlations between FEV1% and Ryan score (r = -0.394, P < 0.001), FEV1% and % time below pH threshold (r = -0.371, P < 0.001) in upright position but not in supine position. There was no significant correlation between RSI and Ryan score parameters. There were significant improvements in RSI, mMRC, CAT, and FEV1% in Ryan-positive AECOPD patients after PPI and basic treatments.CONCLUSION:Study results indicate unreliability of RSI threshold for LPR diagnosis. Combination of symptoms, endoscopic findings, and 24-hour Dx-pH monitoring is recommended for LPR diagnosis and PPI treatment decisions, especially in difficult-to-control or severe COPD patients.

Overexpression of RING finger protein 187 (RNF187) was recently revealed to be a driver of several cancers. However, the expression and function of RNF187 in non-small-cell lung cancer (NSCLC) are still unknown. Here, we uncovered that RNF187 expression was significantly higher in NSCLC samples than in matched normal lung samples at both the messenger RNA (3.55 ± 0.79 vs. 1.74 ± 0.63) and protein (2.85 ± 0.14 vs. 1.24 ± 0.02) levels. By downregulating or upregulating RNF187 expression in NSCLC cells, we showed that elevated RNF187 expression distinctly enhanced the migration, invasion, and colony formation of NSCLC cells. Moreover, we revealed that high level of RNF187 promoted NSCLC progression by inducing cell epithelial to mesenchymal transition (EMT) and apoptosis resistance mainly via activating the mitogen-activated protein kinase and PI3K signaling. Clinically, we demonstrated that RNF187 expression was positively associated with advanced TNM stage (p = 1.29 × 10 -6 ), lymph node metastasis ( p = 2.69 × 10 -9 ), and large tumor size ( p = 0.002). Importantly, NSCLC patients with elevated RNF187 expression related to the short overall survival rate( p = 1.29, E-7) and could serve as an independent prognostic factor in NSCLC patients. Thus, elevated RNF187 expression promotes NSCLC development by inducing cell EMT and apoptosis resistance, and RNF187 may be a novel prognostic indicator for NSCLC patients after curative resection.