Background Pulmonary embolism (PE) is a leading cause of cardiovascular mortality worldwide. Rapid and accurate diagnosis and risk stratification are crucial for timely treatment options, especially in high‐risk PE. Objectives The study aims to profile the comprehensive changes of plasma proteomes in PE patients and identify the potential biomarkers for both diagnosis and risk stratification. Patients/Methods Based on the data‐independent acquisition mass spectrometry and antibody array proteomic technology, we screened the plasma samples (13 and 32 proteomes, respectively) in two independent studies consisting of high‐risk PE patients, non‐high‐risk PE patients, and healthy controls. Some significantly differentially expressed proteins were quantified by ELISA in a new study group with 50 PE patients and 26 healthy controls. Results We identified 207 and 70 differentially expressed proteins in PE and high‐risk PE. These proteins were involved in multiple thrombosis‐associated biological processes including blood coagulation, inflammation, injury, repair, and chemokine‐mediated cellular response. It was verified that five proteins including SAA1, S100A8, TNC, GSN, and HRG had significant change in PE and/or in high‐risk PE. The receiver operating characteristic curve analysis based on binary logistic regression showed that the area under the curve (AUC) of SAA1, S100A8, and TNC in PE diagnosis were 0.882, 0.788, and 0.795, and AUC of S100A8 and TNC in high‐risk PE diagnosis were 0.773 and 0.720. Conclusion As predictors of inflammation or injury repair, SAA1, S100A8, and TNC are potential plasma biomarkers for the diagnosis and risk stratification of PE.
The integration of HBV DNA into the human genome can disrupt its structure in hepatocellular carcinoma (HCC), but the complexity of HBV genomic integration remains elusive. Here we applied long-read sequencing to precisely elucidate the HBV integration pattern in the human hepatocellular genome. The DNA library was sequenced using the long-read sequencing on GridION and PacBio Sequel II, respectively. The DNA and mRNA were sequenced using next-generation sequencing on Illumina NextSeq. BLAST (Basic Local Alignment Search Tool) and local scripts were used to analyze HBV integration patterns. We established an analytical strategy based on the long-read sequences, and analyzed the complexity of HBV DNA integration into the hepatocellular genome. A total of 88 integrated breakpoints were identified. HBV DNA integration into human genomic DNA was mainly fragmented with different orientations, rarely with a complete genome. The same HBV integration breakpoints were identified among the three platforms. Most breakpoints were observed at P, X, and S genes in the HBV genome, and observed at introns, intergenic sequences, and exons in the human genome. Tumor tissue harbored a much higher integrated number than the adjacent tissue, and the distribution of HBV integrated into human chromosomes was more concentrated. HBV integration shows different patterns between cancer cells and adjacent normal cells. We for the first time obtained the entire HBV integration pattern through long-read sequencing and demonstrated the value of long-read sequencing in detecting the genomic integration structures of viruses in host cells.
Background Thymomas and thymic carcinomas are the most common tumor types among anterior mediastinal lesions. However, the relationship between molecular aberrations and thymoma patients are poorly understood, especially abnormal changes in the expression profiles of circRNAs. The purpose of the present study was to investigate the expression profiles of circRNAs in thymoma patients and their possible roles in the pathogenesis of thymoma. Methods Diseased tissues and surrounding normal thymic tissues in two thymoma patients were collected for circRNA sequencing. The top four upregulated circRNAs were selected as candidates and further validated with RT‐PCR in 20 thymoma patients. Gene ontology and signal transduction network analyses of circRNA‐related mRNAs were performed to analyze the functional properties. Survival analysis of their parental genes were also carried out to evaluate the clinical value of differentially expressed circRNA. Results A total of 73 circRNAs were differentially expressed in thymoma tissues using high‐throughput sequencing. Among these circRNAs, hsa_circ_0001173, hsa_circ_0007291, hsa_circ_0003550, and hsa_circ_0001947 were significantly upregulated in thymoma tissues compared with normal thymic tissues. We identified that these four circRNA‐related mRNAs were involved in cell–cell adhesion, MAPK pathways, and TNF pathway, which may contribute to the pathological immune disorder in thymoma. Finally, we also found that SCAP (hsa_circ_0007291 parental gene) and AFF2 (hsa_circ_0001947 parental gene) were all significantly related with progression‐free survival (PFS) of thymoma patients in a Kaplan‐Meier plot (p‐value <0.05). Conclusions The expression levels of hsa_circ_0001173, hsa_circ_0007291, hsa_circ_0003550, and hsa_circ_0001947 were significantly upregulated and positively correlated with immune imbalance in thymoma patients.
Background: Alcohol-associated liver disease (ALD) increases the health burden worldwide, but effective drugs to prevent ALD are lacking. Furfural is a small molecule that can limit alcohol production in microorganisms and may have the capacity to attenuate ethanol-induced toxicity.Methods: Human HepG2 cells were incubated with ethanol and furfural, and cell viability, NAD+/NADH ratio, and mitochondrial function assays were performed. RNA sequencing (RNA-seq) data were used to annotate enriched pathways, and these findings were confirmed by reverse transcription-quantitative PCR (RT–qPCR) and Western blotting. C57BL/6J mice were fed a Lieber-DeCarli liquid diet. After 4 weeks, biochemical analysis of mouse serum and histological analysis of mouse livers were performed.Results: Different concentrations of furfural exerted different effects on mitochondria: low-dose furfural reduced reactive oxygen species (ROS) production, maintained mitochondrial transmembrane potential, and inhibited apoptosis pathway activation, while high-dose furfural led to the opposite effects. In mice, furfural mitigated transaminase increases and attenuated the lipid metabolism disorder that had been induced by ethanol.Conclusion: Low-dose furfural reduced ethanol-induced toxicity in the liver. Consuming food or beverages containing the appropriate level of furfural when drinking alcohol may be a convenient and useful way to prevent ALD.
ObjectivesGestational thrombocytopenia (GT) is the most common cause of thrombocytopenia during pregnancy. However, the occurrence and severity of thrombocytopenia throughout pregnancy in Chinese women are not fully defined.MethodsWe analyzed platelet counts in Chinese women who received prenatal care and/or delivered at the First Affiliated Hospital with Nanjing Medical University between January 2, 2018 and July 19, 2018 in China. These platelet counts were compared with those of nonpregnant women in the same study period.ResultsThe platelet counts of all women continued to decrease significantly each trimester (p < 0.0001). The mean platelet counts of the 818 women who had pregnancy-related complications were lower than those of the 796 women who had uncomplicated pregnancies during the third trimester (p = 0.047). At the time of delivery, platelet counts less than 150 × 109/L were more common in women with pregnancy-related complications than in women with uncomplicated pregnancy (26.7% vs. 19.7%, p = 0.03).ConclusionsPlatelet counts decrease throughout pregnancy in Chinese women and platelet counts less than 150 × 109/L were more common in women with pregnancy-related complications than in women with uncomplicated pregnancy. The pregnant women should be paid more attention for thrombocytopenia to avoid the occurrence of bleeding events.
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