Immune thrombocytopenia increases the risk of thrombosis: A two-sample Mendelian randomization study.

BACKGROUND: Immune thrombocytopenia (ITP) is a prevalent autoimmune bleeding disorder, with the primary objective of treatment being the prevention of bleeding. Clinical investigations have indicated that individuals with ITP face an elevated risk of thrombosis, and the occurrence of thromboembolic events in ITP patients can be attributed to a multitude of factors. However, establishing a definitive causal relationship between ITP and thrombosis remains challenging. METHODS: A two-sample Mendelian randomization (MR) study utilizing summary data from FinnGen consortium and UK Biobank was undertaken to investigate the causal association between ITP and thrombosis. The primary analysis employed the inverse-variance weighted (IVW) method, while supplementary analyses were conducted using the MR-Egger, weighted median, and MR-PRESSO approaches. RESULTS: Based on IVW method, there was a statistically significant but small positive correlation between ITP and thrombosis. Specifically, ITP patients exhibited a suggestive positive correlation with myocardial infarction and deep-vein thrombosis. However, our investigation did not identify any causal relationship between ITP and cerebral infarction, arterial embolism, other arterial embolisms, pulmonary embolism, thrombophlebitis, or portal vein thrombosis. Sensitivity analyses further confirmed the accuracy and robustness of these findings. CONCLUSIONS: This study presents empirical support for the causal relationship between ITP and thrombosis. It is important to note that a diminished platelet count does not serve as a preventive measure against thrombus formation. Consequently, when managing a newly diagnosed ITP patient, clinicians need to be aware that there is a slight elevation in the risk of thrombosis during treatment.

Association between circadian syndrome and chronic diarrhea: a cross-sectional study of NHANES 2005-2010 data.

Background: Circadian rhythms are reported to influence physiological processes in the gastrointestinal system, but associations between circadian syndrome (Circs) and chronic diarrhea (CD) remain unclear. Here, we explored such relationships to provide new insights into CD management. Methods: We conducted a cross-sectional retrospective analysis using the National Health and Nutrition Examination Survey (NHANES) data between 2005 and 2010. Univariate and multivariable logistic regression analyses were performed on weighted data to explore associations between Circs and CD. Results: Results were presented using forest plots, odds ratios (ORs), and 95% confidence intervals (CIs). Data with p-values < 0.05 were considered statistically significant. In total, 5,661 US participants, of which 412 had CD (weighted percentage = 6.20%), were enrolled. In univariate logistic regression analyses, participants with Circs had a significantly higher risk of CD (OR = 1.51, 95% CI: 1.15-1.99). After adjusting for covariates, model 2 (OR = 1.40, 95% CI: 1.03-1.90) and model 3 (OR = 1.42, 95% CI: 1.01-2.00) data were consistent with model 1 data. Additionally, the number of Circs components was positively associated with CD in all three models. Subgroup analyses revealed an association between CD and Circs in participants who had high blood pressure (OR = 2.46, 95% CI: 1.48-4.11, p < 0.001). Conclusion: In this cross-sectional study, we found that Circs is positively associated with the risk of CD in US adults, especially in those with high blood pressure. This association may provide new management strategies for CD.

A Case of Pseudoelevation of Serum CA19-9 Level.

BACKGROUND: Carbohydrate antigen 19-9 (CA19-9) is usually synthesized by pancreatic and bile duct cells and is present in small amounts in serum. During the period of tumor disease, its serum level significantly increases, and it is the most widely used serum tumor marker for diagnosis and monitoring therapy of pancreatic cancer. METHODS: We reported a case of abnormal elevation of serum CA19-9. Considering the possibility of detection interference, we used heterophilic antibody blocking analysis, detection by different analysis systems, and polyethylene glycol (PEG) precipitation to evaluate the reliability of abnormally elevated CA19-9 concentration. RESULTS: Repeated measurements on the Roche Cobas 8000 system of another hospital significantly reduced the CA19-9 concentration, as did PEG precipitation. Therefore, the abnormally elevated level of CA19-9 in this patient is considered to be pseudoelevation caused by interferences. CONCLUSIONS: We suggest considering the presence of detection interference in cases with elevated CA19-9 levels but no related clinical manifestations to prevent false positives. PEG precipitation may be a simple and feasible solution to eliminate interference.

Detection and Significance of PNC in Breast Cancer Tissues.

BACKGROUND: The PNC (perinucleolar compartment) associates with malignancy of various solid tumors. Our study was to detect the expression level of PNC in breast cancer tissues and analyze the clinical significance. METHODS: Immunohistochemistry and immunofluorescence were used to detect the expression of PNC in breast cancer tissues, para-cancer tissues, and lymph nodes. RESULTS: We used immunohistochemistry to detect PNC in paraffin tissues of breast cancer. PNC was expressed in 66.67% breast cancer tissues and 60.87% lymph node tissues, but not corresponding para-cancer tissues. PNC was not correlated with ER, PR, tumor size, and lymph node infiltration (all p > 0.05), but was correlated with TNM (p < 0.05). Immunofluorescence was used to detect PNC, 64.29% breast cancer tissues and 75% lymph node tissues were positive, but all adjacent tissues were negative. PNC was detected by immunohistochemistry and immunofluorescence in 14 breast cancer tissues and para-cancer tissues simultaneously. Nine cases were positive by immunofluorescence and 6 cases were positive by immunohistochemistry, with a coincidence rate of 66.67%. PNC of para-cancer tissues were detected negative by both methods, and the coincidence rate was 100%. CONCLUSIONS: The expression of PNC in breast cancer tissues was higher than that in para-cancer tissues. There was no significant correlation between PNC and breast cancer invasion and metastasis.

Synergistic effects of olaparib combined with ERCC1 on the sensitivity of cisplatin in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a common malignant tumor. ERCC excision repair 1 endonuclease non-catalytic subunit (ERCC1) is a key mediator of nucleotide excision repair. The present study aimed to explore the synergistic effects of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib combined with ERCC1 on the sensitivity of NSCLC cells to cisplatin. Preliminary experiments were performed to identify the optimal concentrations of cisplatin and olaparib for cellular treatment and subsequently NCI-H1299 and SK-MES-1 cells were treated with 20 µg/ml cisplatin combined with 50 µg/ml olaparib and 50 µg/ml cisplatin combined with 70 µg/ml olaparib, respectively. Subsequently, transfections were carried out to overexpress or knockdown the expression of ERCC1 in NSCLC cell lines, including NCI-H1299 and SK-MES-1. The transfection efficiency was evaluated using reverse transcription-quantitative PCR and western blotting. The results demonstrated that cells with ERCC1 overexpression and ERCC1 knockdown were successfully constructed. Finally, the cell viability and apoptosis were determined using the Cell Counting Kit-8 and Annexin V-FITC cell apoptosis assays, respectively. In NCI-H1299 or SK-MES-1 cells treated with cisplatin combined with olaparib for 24 h, the cell viability significantly increased following ERCC1 overexpression compared with the GV230 group (P<0.05), but significantly inhibited following ERCC1 knockdown compared with the siRNA-NC group (P<0.05). However, ERCC1 overexpression or knockdown had the opposite effect on apoptosis. In conclusion, olaparib combined with ERCC1 expression may enhance the sensitivity of cisplatin in NSCLC. These findings may provide novel insight for the improvement of platinum drug sensitivity and treatment of NSCLC.

NUF2 as an anticancer therapeutic target and prognostic factor in breast cancer.

Breast cancer (BC) is the most frequently diagnosed type of cancer, and the leading cause of cancer­associated mortality in females worldwide. The aim of the present study was to investigate the prognostic and therapeutic potential of NUF2 in BC. The expression levels of NUF2 in BC tissues and cell lines were evaluated via bioinformatics, reverse transcription­quantitative PCR, western blot analysis and immunohistochemistry (IHC). In addition, the effect of NUF2 knockdown on BC cell proliferation and apoptosis was investigated using small interfering RNA (siRNA) technology. Bioinformatics and IHC analysis showed that NUF2 was overexpressed in BC tissues. Furthermore, western blot and RT­qPCR analyses demonstrated that NUF2 was upregulated in BC cells. In addition, BC cells transfected with NUF2 siRNA exhibited significantly decreased proliferation and colony formation, and increased apoptosis, compared with the control. Additionally, cell cycle analysis revealed that NUF2 induced G0/G1 cell cycle arrest by inhibiting cyclin B1 expression. Collectively, the present study suggested that NUF2 may represent a promising prognostic biomarker and a potential therapeutic target for BC.

Serum Exosomal miR-17-5p as a Promising Biomarker Diagnostic Biomarker for Breast Cancer.

BACKGROUND: The biological role of exosomes has attracted widespread attention in various fields of biomedicine. Exosome-delivered microRNAs (miRNAs) play crucial roles in cancer diagnosis. The aim of our study was to examine whether serum exosomal miR-17-5p could be identified as a diagnostic biomarker for breast cancer (BC). METHODS: Eighty-three patients diagnosed with BC and thirty-four healthy women (controls) were included in this study. The expression level of serum exosomal miR-17-5p was identified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and calculated by 2-ΔΔCq method. RESULTS: Reduced level of exosomal miR-17-5p in serum from BC patients was found compared with healthy controls. In addition, miR-17-5p also had low expression in 34 pairs of tissue and serum samples. MiR-17-5p was highly concentrated in serum exosomes and the expression level was stable. In addition, the exosomal miR-17-5p could distinguish BC from healthy controls with the area under the ROC curve (AUC) of 0.784 (p < 0.0001, sensi¬tivity = 66.67%, specificity = 83.95%). The sensitivity and specificity of miR-17-5p were superior to conventional se¬rum biomarkers CEA, CA125, and CA153. We predicted target genes of miR-17-5p were also mainly involved in cancer-related pathways. CONCLUSIONS: In conclusion, our findings strongly suggested that serum exosomal miR-17-5p could serve as a novel diagnostic biomarker for BC.

Screening of differentially expressed genes and identification of NUF2 as a prognostic marker in breast cancer.

The aims of the present study were to screen differentially expressed genes (DEGs) in breast cancer (BC) and investigate NDC80 kinetochore complex component (NUF2) as a prognostic marker of BC in detail. A total of four BC microarray datasets, downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, were used to screen DEGs. A total of 190 DEGs with the same expression trends were identified in the 4 datasets, including 65 upregulated and 125 downregulated DEGs. Functional and pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery. The upregulated DEGs were enriched for 10 Gene Ontology (GO) terms and 7 pathways, and the downregulated DEGs were enriched for 10 GO terms and 10 pathways. A protein­protein interaction network containing 149 nodes and 930 edges was constructed using the Search Tool for the Retrieval of Interacting Genes, and 2 functional modules were identified using the MCODE plugin of Cytoscape. Based on an in­depth analysis of module 1 and literature mining, NUF2 was selected for further research. Oncomine database analysis and reverse transcription­quantitative PCR showed that NUF2 is significantly upregulated in BC tissues. In analyses of correlations between NUF2 and clinical pathological characteristics, NUF2 was significantly associated with the malignant features of BC. Using 5 additional datasets from GEO, it was demonstrated that NUF2 has a significant prognostic role in both ER­positive and ER­negative BC. A Gene Set Enrichment Analysis indicated that NUF2 may regulate breast carcinogenesis and progression via cell cycle­related pathways. The results of the present study demonstrated that NUF2 is overexpressed in BC and is significantly associated with its multiple pathological features and prognosis.

miR-17-5p promotes migration and invasion in breast cancer cells by repressing netrin 4.

Netrin 4 (NTN4) is downregulated in breast cancer (BC) and can inhibit the migration of BC cells. miRNAs dysregulation plays prominent roles in BC tumorigenesis. However, the function of miR-17-5p, its relationship with NTN4 and its underlying functional mechanism in BC are unclear and were investigated in the current study. Compared with normal breast samples, miR-17-5p was upregulated in BC specimens in The Cancer Genome Atlas (TCGA). A clinical analysis based on TCGA showed that miR-17-5p expression correlated with BC tumor stage, lymph node status, estrogen receptor, and progesterone receptor status. A wound-healing assay and Transwell assay implied that miR-17-5p upregulation promotes BC cell migration and invasion. Reverse transcription-quantitative PCR and ELISA showed that NTN4 mRNA and protein were both downregulated after miR-17-5p was overexpressed in Hs578T cells, whereas miR-17-5p inhibition had the opposite effect in MCF-7 cells. We also performed a dual-fluorescent reporter assay, the results of which demonstrated that miR-17-5p represses NTN4 expression by directly targeting the 3' untranslated region of NTN4 mRNA. In summary, miR-17-5p considerably promotes BC cell migration by suppressing NTN4 expression, and may therefore offer a potential therapeutic target for BC.