46 research outputs found

    Vitamin D and cause-specific vascular disease and mortality:a Mendelian randomisation study involving 99,012 Chinese and 106,911 European adults

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    Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

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    Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

    LncHOXA10 drives liver TICs self-renewal and tumorigenesis via HOXA10 transcription activation

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    Abstract Background Liver cancer is one of the most deadly cancers in the world. There are various cells in liver tumor bulk, including liver tumor initiating cells (TICs), which account for liver tumorigenesis, drug resistance, relapse and metastasis. The homeobox (HOX) transcription factors play critical roles in many physiological and pathological processes, while, their roles in liver TICs and liver tumorigenesis remain unknown. Methods An unbiased screening was performed using online-available datasets. Liver TICs were sorted by FACS using surface markers CD133, CD13 and EPCAM, or enriched by oncosphere formation assay. TIC self-renewal was examined by oncosphere formation and tumor initiation assay. Loss of function and gain of function assays were performed to examine the role of lncRNA. RNA pulldown, RNA immunoprecipitation, ChIP, Western blot and double FISH were used to explore the molecular mechanism of lncRNA. Results Here, we examined the expression pattern of HOX transcription factors, and found HOXA10 was overexpressed in liver cancer samples. Moreover, a divergent lncRNA of HOXA10 (termed lncHOXA10 hereafter) was also highly expressed in liver cancer and liver TICs. LncHOXA10 drove liver TIC self-renewal and liver tumorigenesis through HOXA10-dependent manner. LncHOXA10 interacted with SNF2L and recruited NURF chromatin remodeling complex to HOXA10 promoter, and thus initiated the transcription of HOXA10. Through HOXA10 transcriptional regulation, lncHOXA10 activated HOXA10 in liver TICs. LncHOXA10-HOXA10 signaling can be targeted to eliminate liver TICs. Altogether, lncHOXA10 drove HOXA10 expression and thus promoted liver TIC self-renewal. Conclusion HOXA10 was the most highly expressed HOX transcription factor in liver cancer and liver TICs. LncHOXA10 drove the transcriptional activation of HOXA10. This work revealed the important role of HOX transcription factor in liver TIC self-renewal and added a new layer for liver TIC regulation

    Investigation heme oxygenase-1 polymorphism with the pathogenesis of preeclampsia

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    Objectives: The involvement of oxidative stress in the pathophysiology of preeclampsia (PE) has been already suggested. In this present study, we aimed to investigate the association of the genetic frequency of heme oxygense-1 (HMOX1) polymorphism with PE in Chinese Han women. Methods: We researched the genetic distribution of rs2071746 polymorphism in HMOX1 by the TaqMan allelic discrimination real-time PCR between 1235 PE patients and 1720 healthy women. Results: We found there were′t significant differences in the distribution of HMOX1 rs2071746 polymorphism in PE compared to the control group (rs2071746, genotype χ2 = 0.282, P = 0.869 and allele χ2 = 0.027, P = 0.869, OR = 1.009, 95% = 0.909–1.120). Conclusion: The rs2071746 polymorphism in HMOX1 might not be related to PE in Chinese women, although further investigations should be conducted to confirm our findings

    Leveraging deep learning to identify calcification and colloid in thyroid nodules

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    Background: Both calcification and colloid in thyroid nodules are reflected as echogenic foci in ultrasound images. However, calcification and colloid have significantly different probabilities of malignancy. We explored the performance of a deep learning (DL) model in distinguishing the echogenic foci of thyroid nodules as calcification or colloid. Methods: We conducted a retrospective study using ultrasound image sets. The DL model was trained and tested on 30,388 images of 1127 nodules. All nodules were pathologically confirmed. The area under the receiver-operator characteristic curve (AUC) was employed as the primary evaluation index. Results: The YoloV5 (You Only Look Once Version 5) transfer learning model for thyroid nodules based on DL detection showed that the average sensitivity, specificity, and accuracy of distinguishing echogenic foci in the test 1 group (n = 192) was 78.41%, 91.36%, and 77.81%, respectively. The average sensitivity, specificity, and accuracy of the three radiologists were 51.14%, 82.58%, and 61.29%, respectively. The average sensitivity, specificity, and accuracy of distinguishing small echogenic foci in the test 2 group (n = 58) was 70.17%, 77.14%, and 73.33%, respectively. Correspondingly, the average sensitivity, specificity, and accuracy of the radiologists were 57.69%, 63.29%, and 59.38%. Conclusions: The study demonstrated that DL performed far better than radiologists in distinguishing echogenic foci of thyroid nodules as calcifications or colloid

    Genome-wide methylation profiling identify hypermethylated HOXL subclass genes as potential markers for esophageal squamous cell carcinoma detection

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    Abstract Background Numerous studies have revealed aberrant DNA methylation in esophageal squamous cell carcinoma (ESCC). However, they often focused on the partial genome, which resulted in an inadequate understanding of the shaped methylation features and the lack of available methylation markers for this disease. Methods The current study investigated the methylation profiles between ESCC and paired normal samples using whole-genome bisulfite sequencing (WGBS) data and obtained a group of differentially methylated CpGs (DMC), differentially methylated regions (DMR), and differentially methylated genes (DMG). The DMGs were then verified in independent datasets and Sanger sequencing in our custom samples. Finally, we attempted to evaluate the performance of these genes as methylation markers for the classification of ESCC. Results We obtained 438,558 DMCs, 15,462 DMRs, and 1568 DMGs. The four significantly enriched gene families of DMGs were CD molecules, NKL subclass, HOXL subclass, and Zinc finger C2H2-type. The HOXL subclass homeobox genes were observed extensively hypermethylated in ESCC. The HOXL-score estimated by HOXC10 and HOXD1 methylation, whose methylation status were then confirmed by sanger sequencing in our custom ESCC samples, showed good ability in discriminating ESCC from normal samples. Conclusions We observed widespread hypomethylation events in ESCC, and the hypermethylated HOXL subclass homeobox genes presented promising applications for the early detection of esophageal squamous cell carcinoma
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