Background and Purpose: Hypertensive disorders of pregnancy (HDP) comprise 4 subtypes. Previous studies have not investigated the relationship between stroke risk, different HDP subtypes, and follow-up time, which was the purpose of this study. Methods: Data of 17 588 women aged 18 to 45 years who had a history of HDP in Taiwan from 2000 to 2017 was retrospectively reviewed. After matching with confounders, 13 617 HDP women and 54 468 non-HDP women were recruited. Results: HDP women had an adjusted hazard ratio (aHR) of 1.71 (95% CI, 1.46−2.00) for stroke, and 1.60 (1.35−1.89) and 2.98 (2.13−4.18) for ischemic and hemorrhagic stroke, respectively ( P <0.001 for all). The overall stroke risk in the HDP group was still 2.04 times 10 to 15 years after childbirth (1.47−2.83, P <0.001). Although the risks of both ischemic and hemorrhagic stroke persisted, their risk time trends were different. The risk of ischemic stroke reached peak during 1 to 3 years after childbirth with an aHR of 2.14 (1.36–3.38), while hemorrhagic stroke risk gradually increased and had an aHR of 4.64 (2.47−8.73) after 10 to 15 years of childbirth (both P <0.001). Among the 4 HDP subtypes, chronic hypertension with superimposed preeclampsia had the highest stroke risk (aHR=3.86, 1.91−7.82, P <0.001), followed by preeclampsia–eclampsia (aHR=2.00, 1.63−2.45, P <0.001), and gestational hypertension (aHR=1.68, 1.13−2.52, P <0.05); chronic preexisting hypertension had the lowest stroke risk (aHR=1.27, 0.97−1.68, P >0.05). Furthermore, multiple HDP combined with preeclampsia had aHR of 5.48 (1.14−26.42, P <0.05). Conclusions: The effect of HDP on the risk of future stroke persisted for up to 17 years, both for ischemic and hemorrhagic strokes. The presence of multiple HDP and preeclampsia further increase the stroke risk.
Predicting and overcoming radioresistance are crucial in radiation oncology, including in managing oral squamous cell carcinoma (OSCC). First, we used RNA-sequence to compare expression profiles of parent OML1 and radioresistant OML1-R OSCC cells in order to select candidate genes responsible for radiation sensitivity. We identified IRAK2, a key immune mediator of the IL-1R/TLR signaling, as a potential target in investigating radiosensitivity. In four OSCC cell lines, we observed that intrinsically low IRAK2 expression demonstrated a radioresistant phenotype (i.e., OML1-R and SCC4), and vice versa (i.e., OML1 and SCC25). Next, we overexpressed IRAK2 in low IRAK2-expression OSCC cells and knocked it down in high IRAK2-expression cells to examine changes of irradiation response. After ionizing radiation (IR) exposure, IRAK2 overexpression enhanced the radiosensitivity of radioresistant cells and synergistically suppressed OSCC cell growth both in vitro and in vivo, and vice versa. We found that IRAK2 overexpression restored and enhanced radiosensitivity by enhancing IR-induced cell killing via caspase-8/3-dependent apoptosis. OSCC patients with high IRAK2 expression had better post-irradiation local control than those with low expression (i.e., 87.4% vs. 60.0% at five years, P = 0.055), showing that IRAK2 expression was associated with post-radiation recurrence. Multivariate analysis confirmed high IRAK2 expression as an independent predictor for local control (HR, 0.11; 95% CI, 0.016 – 0.760; P = 0.025). In conclusion, IRAK2 enhances radiosensitivity, via modulating caspase 8/3-medicated apoptosis, potentially playing double roles as a predictive biomarker and a novel therapeutic target in OSCC.
BackgroundThe role of interleukin (IL) 17A in chronic liver diseases had been extensively studied, but the function of IL-17F, which shares a high degree of homology with IL-17A, in the progression of chronic hepatic diseases is poorly understood. The aim of the study was to evaluate the association between IL-17F and liver diseases including, fibrosis and hepatocellular carcinoma (HCC).MethodsHepatic tumor samples from both hepatitis C virus (HCV) positive and negative patients (without HBV and HCV, NBNC) were examined with quantitative PCR and immunohistochemistry staining for inflammatory cytokine genes expression. In addition, 250 HCV patients naïve for interferon treatment were also subjected to enzyme-linked immunosorbent Assay (ELISA) for their serum cytokine concentrations.ResultsSerum IL-17F concentrations were significantly elevated in HCV patients with severe fibrosis stages. In accordance with serum data, IL-17F expression was also found higher in HCV-associated HCC tissues compared with NBNC HCC tissues at both the mRNA and protein levels.ConclusionsOur data suggest that IL-17F might be used as a valuable biological marker than IL-17A during chronic fibrosis progression and HCC development in HCV patients.
Background and purposes The long-term risk of stroke in women with preeclampsia/eclampsia is a concerning issue. In this study we further investigated different stroke subtypes and differentiated follow-up time intervals. Methods Between 2000 and 2017, 1,384,427 pregnant women were registered in the National Health Insurance Research Database in Taiwan. After excluding women with previous stroke history and exact matching with all confounders, 6,053 women with preeclampsia/eclampsia and 24,212 controls were included in the analysis sample. Results Over the 17-year follow-up, the adjusted hazard ratio (aHR) for stroke in women with preeclampsia/eclampsia was 2.05 (95% confidence interval, CI = 1.67–2.52, p<0.001). The 17 years overall aHR of both ischemic and hemorrhagic stroke were 1.98 and 3.45, respectively (p<0.001). The stroke subtypes, hemorrhagic and ischemic, had different time trend risks, and hemorrhagic stroke risks kept higher than that of ischemic stroke. The aHR of ischemic stroke reached a peak during 1–3 years after childbirth (aHR = 3.09). The aHR of hemorrhagic stroke reached a peak during 3–5 years (aHR = 7.49). Conclusions Stroke risk persisted even after decades, for both ischemic and hemorrhagic subtypes. Women with preeclampsia/eclampsia history should be aware of the long-term risk of stroke.
Gene Ontology (GO) analysis can provide a comprehensive function analysis for investigating genes, allowing us to identify the potential biological roles of genes. The present study conducted GO analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in disease progression and mediating tumor response to RT. Methods: We performed a GO enrichment analysis on the RNA-seq data to validate radiation-induced gene expression. A total of 172 I-IVB specimens from oral squamous cell carcinoma patients were collected for clinical analysis, from which IRAK2 expression was analyzed by immunohistochemistry. This was a retrospective study conducted between IRAK2 expression and the outcomes of oral squamous cell carcinoma patients after radiotherapy treatment. We conducted Gene Ontology (GO) analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in mediating tumor response to radiotherapy. GO enrichment analysis to validate radiation-induced gene expression was performed. Clinically, 172 stage I-IVB resected oral cancer patients were used to validate IRAK2 expression in predicting clinical outcomes. GO enrichment analysis showed that IRAK2 is involved in 10 of the 14 most enriched GO categories for post-irradiation biological processes, focusing on stress response and immune modulation. Clinically, high IRAK2 expression was correlated with adverse disease features, including pT3-4 status (p = 0.01), advanced overall stage (p = 0.02), and positive bone invasion (p = 0.01). In patients who underwent radiotherapy, the IRAK2-high group was associated with reduced post-irradiation local recurrence (p = 0.025) compared to the IRAK2-low group. IRAK2 plays a crucial role in the radiation-induced response. Patients with high IRAK2 expression demonstrated more advanced disease features but predicted higher post-irradiation local control in a clinical setting. These findings support IRAK2 as a potential predictive biomarker for radiotherapy response in non-metastatic and resected oral cancer patients.
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