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Background: Polypharmacy is common among older people and is associated with an increased mortality risk. However, little is known about whether the mortality risk is related to specific medications among older adults with polypharmacy. This study therefore aimed to investigate associations between high-risk medications and all-cause and cause-specific mortality among older adults with polypharmacy.Methods: This study included 1356 older adults with polypharmacy (5+ long-term medications a day for conditions or symptoms) from Wave 6 (2012/2013) of the English Longitudinal Study of Ageing. First, using the agglomerative hierarchical clustering method, participants were grouped according to the use of 14 high-risk medication categories. Next, the relationship between the high-risk medication patterns and all-cause and cause-specific mortality (followed up to April 2018) was examined. All-cause mortality was assessed by Cox proportional hazards model and competing-risk regression was employed for cause-specific mortality.Results: Five high-risk medication patterns-a renin-angiotensin-aldosterone system (RAAS) inhibitors cluster, a mental health drugs cluster, a central nervous system (CNS) drugs cluster, a RAAS inhibitors and antithrombotics cluster, and an antithrombotics cluster-were identified. The mental health drugs cluster showed increased risks of all-cause (HR = 1.55, 95%CI = 1.05, 2.28) and cardiovascular disease (CVD) (SHR = 2.11, 95%CI = 1.10, 4.05) mortality compared with the CNS drug cluster over 6 years, while others showed no differences in mortality. Among these patterns, the mental health drugs cluster showed the highest prevalence of antidepressants (64.1%), benzodiazepines (10.4%), antipsychotics (2.4%), antimanic agents (0.7%), opioids (33.2%), and muscle relaxants (21.5%). The findings suggested that older adults with polypharmacy who took mental health drugs (primarily antidepressants), opioids, and muscle relaxants were at higher risk of all-cause and CVD mortality, compared with those who did not take these types of medications.Conclusions: This study supports the inclusion of opioids in the current guidance on structured medication reviews, but it also suggests that older adults with polypharmacy who take psychotropic medications and muscle relaxants are prone to adverse outcomes and therefore may need more attention. The reinforcement of structured medication reviews would contribute to early intervention in medication use which may consequently reduce medication-related problems and bring clinical benefits to older adults with polypharmacy. [ABSTRACT FROM AUTHOR]

Background: To evaluate the impact of oral carbohydrate-rich (Ch-R) supplement taken 2 hours before an elective caesarean delivery (CD) on maternal and neonatal perioperative outcomes.Methods: Ninety pregnant women undergoing elective CD were randomized into the Ch-R group, placebo group and fasting group equally. Participants' blood was drawn at three time points, before intervention, immediately after and 1 day after the surgery to measure maternal and neonatal biochemical indices. Meanwhile women's perioperative symptoms and signs were recorded.Results: Eighty-eight pregnant women were finally included in the study. Women who had drunk Ch-R supplement had lower postoperative insulin level (β = - 3.50, 95% CI - 5.45 to - 1.56), as well as postoperative HOMA-IR index (β = - 0.74, 95% CI - 1.15 to - 0.34), compared with women who had fasted. Additionally, neonates of mothers who were allocated in the Ch-R group also had a higher glucose level, compared with neonates of mothers in the fasting group (β = 0.40, CI 0.17 to 0.62).Conclusion: Oral Ch-R solution administered 2 hours before an elective CD may not only alleviate maternal postoperative insulin resistance, but also comfort women's preoperative thirst and hunger, compared to fasting. Additionally, it may increase neonatal glucose level as well.Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000033163 . Data of Registration: 2020-5-22. [ABSTRACT FROM AUTHOR]

Background: Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the stroke care systems have been seriously affected because of social restrictions and other reasons. As the pandemic continues to spread globally, it is of great significance to understand how COVID-19 affects the stroke care systems in mainland China.Methods: We retrospectively studied the real-world data of one comprehensive stroke center in mainland China from January to February 2020 and compared it with the data collected during the same period in 2019. We analyzed DTN time, onset-to-door time, severity, effects after treatment, the hospital length of stays, costs of hospitalization, etc., and the correlation between medical burden and prognosis of acute ischemic stroke (AIS) patients.Results: The COVID-19 pandemic was most severe in mainland China in January and February 2020. During the pandemic, there were no differences in pre-hospital or in-hospital workflow metrics (all p>0.05), while the degree of neurological deficit on admission and at discharge, the effects after treatment, and the long-term prognosis were all worse (all p<0.05). The severity and prognosis of AIS patients were positively correlated with the hospital length of stays and total costs of hospitalization (all p<0.05).Conclusions: COVID-19 pandemic is threatening the stroke care systems. Measures must be taken to minimize the collateral damage caused by COVID-19. [ABSTRACT FROM AUTHOR]

Background: Super-enhancers (SEs) play a crucial role in cancer, which is often associate with activated oncogenes. However, little is known about how SEs facilitate tumour suppression. Individuals with Down syndrome exhibit a remarkably reduced incidence of breast cancer (BC), moving the search for tumor suppressor genes on human chromosome 21 (HSA21). In this study, we aim to identify and explore potential mechanisms by which SEs are established for tumor suppressor RCAN1.4 on HSA21 in BC. Methods: In silico analysis and immunohistochemical staining were used to assess the expression and clinical relevance of RCAN1.4 and RUNX3 in BC. Function experiments were performed to evaluate the effects of RCAN1.4 on the malignancy of breast carcinoma in vitro and in vivo. ChIP-seq data analysis, ChIP-qPCR, double-CRISPR genome editing, and luciferase reporter assay were utilized to confirm RUNX3 was involved in regulating RCAN1.4-associated SE in BC. The clinical value of co-expression of RCAN1.4 and RUNX3 was evaluated in BC patients. Results: Here, we characterized RCAN1.4 as a potential tumour suppressor in BC. RCAN1.4 loss promoted tumour metastasis to bone and brain, and its overexpression inhibited tumour growth by blocking the calcineurin-NFATc1 pathway. Unexpectedly, we found RCAN1.4 expression was driven by a ~ 23 kb-long SE. RCAN1.4-SEdistal was sensitive to BRD4 inhibition, and its deletion decreased RCAN1.4 expression by over 90% and induced the malignant phenotype of BC cells. We also discovered that the binding sites in the SE region of RCAN1.4 were enriched for consensus sequences of transcription factor RUNX3. Knockdown of RUNX3 repressed the luciferase activity and also decreased H3K27ac enrichment binding at the SE region of RCAN1.4. Furthermore, abnormal SE-driven RCAN1.4 expression mediated by RUNX3 loss could be physiologically significant and clinically relevant in BC patients. Notably, we established a prognostic model based on RCAN1.4 and RUNX3 co-expression that effectively predicted the overall survival in BC patients. Conclusions: These findings reveal an important role of SEs in facilitating tumour suppression in BC. Considering that the combination of low RCAN1.4 and low RUNX3 expression has worse prognosis, RUNX3-RCAN1.4 axis maybe a novel prognostic biomarker and therapeutic target for BC patients. [ABSTRACT FROM AUTHOR]

Background: Anopheles sinensis is an important malaria vector in Southeast Asia. The widespread emergence of insecticide resistance in this mosquito species poses a serious threat to the efficacy of malaria control measures, particularly in China. Recently, the whole-genome sequencing and de novo assembly of An. sinensis (China strain) has been finished. A series of insecticide-resistant studies in An. sinensis have also been reported. There is a growing need to integrate these valuable data to provide a comprehensive database for further studies on insecticide-resistant management of An. sinensis. Results: A bioinformatics database named An. sinensis genome database (ASGDB) was built. In addition to being a searchable database of published An. sinensis genome sequences and annotation, ASGDB provides in-depth analytical platforms for further understanding of the genomic and genetic data, including visualization of genomic data, orthologous relationship analysis, GO analysis, pathway analysis, expression analysis and resistance-related gene analysis. Moreover, ASGDB provides a panoramic view of insecticide resistance studies in An. sinensis in China. In total, 551 insecticide-resistant phenotypic and genotypic reports on An. sinensis distributed in Chinese malariaendemic areas since the mid-1980s have been collected, manually edited in the same format and integrated into OpenLayers map-based interface, which allows the international community to assess and exploit the high volume of scattered data much easier. The database has been given the URL: http://www.asgdb.org/. Conclusions: ASGDB was built to help users mine data from the genome sequence of An. sinensis easily and effectively, especially with its advantages in insecticide resistance surveillance and control. [ABSTRACT FROM AUTHOR]