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Background The longitudinal relationship of albuminuria with incident frailty remains unknown. Therefore we aimed to evaluate the relation of albuminuria with the risk of incident frailty in older adults. Methods A total of 1115 participants ≥65 years of age (average age 80.3 years) who were free of frailty in the Chinese Longitudinal Healthy Longevity Survey were included. The outcome was incident frailty, defined as a frailty index ≥0.25 during follow-up. Cox proportional hazards models were used to assess the association of the urinary albumin:creatinine ratio (UACR) with frailty. Results During a median follow-up duration of 5.3 years, 295 (26.5%) participants developed incident frailty. Overall, the UACR was significantly positively associated with the risk of incident frailty (P for trend = 0.005), with a significantly higher risk of incident frailty in participants in the quartile 4 of UACR {≥13.43 mg/g; hazard ratio [HR] 1.64 [95% confidence interval (CI) 1.13–2.37]} compared with those in quartile 1 (<0.73 mg/g). Consistently, when UACRs were assessed as clinical categories, compared with participants with UACR <10 mg/g, those with UACR ≥30 mg/g had a higher HR of incident frailty [HR 1.61 (95% CI 1.17–2.20)]. Accounting for the competing risk of death also did not substantially change the results. In addition, a stronger positive association between UACR and incident frailty was found in those with a higher high-sensitivity C-reactive protein level (hs-CRP) (P for interaction = 0.045). Conclusion Albuminuria was positively associated with the risk of incident frailty, particularly in those with higher hs-CRP, emphasizing the importance of managing both albuminuria and inflammation for primary prevention of frailty. [ABSTRACT FROM AUTHOR]

Increasing evidences show the clinical significance of the interaction between hypoxia and immune in clear cell renal cell carcinoma (ccRCC) microenvironment. However, reliable prognostic signatures based on a combination of hypoxia and immune have not been well established. Moreover, many studies have only used RNA-seq profiles to screen the prognosis feature of ccRCC. Presently, there is no comprehensive analysis of multiomics data to mine a better one. Thus, we try and get it. First, t-SNE and ssGSEA analysis were used to establish tumor subtypes related to hypoxia-immune, and we investigated the hypoxia-immune–related differences in three types of genetic or epigenetic characteristics (gene expression profiles, somatic mutation, and DNA methylation) by analyzing the multiomics data from The Cancer Genome Atlas (TCGA) portal. Additionally, a four-step strategy based on lasso regression and Cox regression was used to construct a satisfying prognostic model, with average 1-year, 3-year and 5-year areas under the curve (AUCs) equal to 0.806, 0.776 and 0.837. Comparing it with other nine known prognostic biomarkers and clinical prognostic scoring algorithms, the multiomics-based signature performs better. Then, we verified the gene expression differences in two external databases (ICGC and SYSU cohorts). Next, eight hub genes were singled out and seven hub genes were validated as prognostic genes in SYSU cohort. Furthermore, it was indicated high-risk patients have a better response for immunotherapy in immunophenoscore (IPS) analysis and TIDE algorithm. Meanwhile, estimated by GDSC and cMAP database, the high-risk patients showed sensitive responses to six chemotherapy drugs and six candidate small-molecule drugs. In summary, the signature can accurately predict the prognosis of ccRCC and may shed light on the development of novel hypoxia-immune biomarkers and target therapy of ccRCC. [ABSTRACT FROM AUTHOR]

The pandemic of coronavirus disease 2019 (COVID-19) urgently calls for more sensitive molecular diagnosis to improve sensitivity of current viral nuclear acid detection. We have developed an anchor primer (AP)-based assay to improve viral RNA stability by bioinformatics identification of RNase-binding site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and implementing AP dually targeting the N gene of SARS-CoV-2 RNA and RNase 1, 3, 6. The arbitrarily primed polymerase chain reaction (AP-PCR) improvement of viral RNA integrity was supported by (a) the AP increased resistance of the targeted gene (N gene) of SARS-CoV-2 RNA to RNase treatment; (b) the detection of SARS-CoV-2 RNA by AP-PCR with lower cycle threshold values (−2.7 cycles) compared to two commercially available assays; (c) improvement of the viral RNA stability of the ORF gene upon targeting of the N gene and RNase. Furthermore, the improved sensitivity by AP-PCR was demonstrated by detection of SARS-CoV-2 RNA in 70–80% of sputum, nasal, pharyngeal swabs and feces and 36% (4/11) of urine of the confirmed cases (n  = 252), 7% convalescent cases (n  = 54) and none of 300 negative cases. Lastly, AP-PCR analysis of 306 confirmed and convalescent cases revealed prolonged presence of viral loading for >20 days after the first positive diagnosis. Thus, the AP dually targeting SARS-CoV-2 RNA and RNase improves molecular detection by preserving SARS-CoV-2 RNA integrity and reveals the prolonged viral loading associated with older age and male gender in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background Data on the association between visit-to-visit variability (VVV) in blood pressure (BP) and the risk of chronic kidney disease (CKD) in general treated hypertensive patients were limited. We aimed to evaluate the relation of VVV in BP with the development of CKD, and examine any possible effect modifiers in hypertensive patients without prior cardiovascular diseases (CVDs) or CKD. Methods This is a post hoc analysis of the Renal Sub-study of the China Stroke Primary Prevention Trial (CSPPT). A total of 10 051 hypertensives without CVD and CKD and with at least six visits of BP measurements from randomization to the 24-month visit were included. The main VVV in BP was expressed as standard deviation (SD). The primary outcome was the development of CKD, defined as a decrease in estimated glomerular filtration rate ≥30% and to a level of <60 mL/min/1.73 m2, or end-stage renal disease. Results The median treatment duration was 4.4 years. After multivariable adjustment, including baseline systolic blood pressure (SBP) and mean SBP during the first 2-year treatment period, there was a significantly positive relationship of SD of SBP with the risk of CKD development (per SD increment; odds ratio, 1.27; 95% confidence interval: 1.10–1.46). The results were similar for coefficient of variation (CV) of SBP. Results across various subgroups, including age, sex, SBP at baseline, treatment compliance, concomitant antihypertensive medications and mean SBP during the first 24-month treatment period, were consistent. Conclusions SBP variability, irrespective of mean BP level, was significantly associated with the development of CKD in general treated hypertensive patients. [ABSTRACT FROM AUTHOR]

Syngnathids (seahorses, pipefishes and seadragons) exhibit an array of morphological innovations including loss of pelvic fins, a toothless tubular mouth and male pregnancy. They comprise two subfamilies: Syngnathinae and Nerophinae. Genomes of three Syngnathinae members have been analyzed previously. In this study, we have sequenced the genome of a Nerophinae member, the Manado pipefish (Microphis manadensis), which has a semi-enclosed brood pouch. Comparative genomic analysis revealed that the molecular evolutionary rate of the four syngnathids is higher than that of other teleosts. The loss of all but one P/Q-rich SCPP gene in the syngnathids suggests a role for the lost genes in dentin and enameloid formation in teleosts. Genome-wide comparison identified a set of 118 genes with parallel identical amino acid substitutions in syngnathids and placental mammals. Association of some of these genes with placental and embryonic development in mammals suggests a role for them in syngnathid pregnancy. [ABSTRACT FROM AUTHOR]

Background Prenatal stress (PRS) is considered a risk factor for depressive disorder. Adult hippocampal neurogenesis is believed to play a role in the regulation of affective behaviors. GABAergic interneuron is a key modulator in adult hippocampal neurogenesis. Growing evidence indicates that PRS has adverse effects on adult hippocampal neurogenesis and DNA epigenetic modifications of the GABAergic system. The aim of this study was to investigate whether epigenetic GABAergic dysfunction participates in the negative impact of PRS on adult hippocampal neurogenesis and related emotional behaviors. Methods Behavioral tests were used to explore PRS-induced depression-like behaviors of adult female mice. Immunohistochemistry staining, real-time reverse transcription-polymerase chain reaction, western blot, and chromatin immunoprecipitation were employed to detect adult neurogenesis and epigenetic changes of the GABAergic system in the hippocampus of PRS mice. Results PRS mice developed a depression phenotype accompanied by the inhibited maturation of hippocampal newborn neurons. Compared with control mice, PRS mice showed decreased expression of glutamic acid decarboxylase 67 at the mRNA and protein levels. GABAA receptor agonist phenobarbital could rectify the decrease of 5-bromo-2-deoxyuridine/neuronal nuclei double-positive (BrdU+/NeuN+) cells in PRS mice. PRS mice also showed increased expression of DNA methyltransferase 1 and increased binding of DNA methyltransferase 1 to glutamic acid decarboxylase 67 promoter region. The treatment with DNA methyltransferase 1 inhibitor 5-aza-deoxycytidine restored the decrease of BrdU+/NeuN+ cells and depression-like behaviors in PRS mice via improving GABAergic system. Conclusions The present results indicate that epigenetic changes of the GABAergic system are responsible for adult hippocampus neurogenesis and depression-like behaviors in PRS mice. [ABSTRACT FROM AUTHOR]

Background Prenatal stress is considered a risk factor for anxiety disorder. Downregulation in the expression of GABAergic gene, that is, glutamic acid decarboxylase 67, associated with DNA methyltransferase overexpression in GABAergic neurons has been regarded as a characteristic component of anxiety disorder. Prenatal stress has an adverse effect on the development of the basolateral amygdala, which is a key region in anxiety regulation. The aim of this study is to analyze the possibility of epigenetic alterations of GABAergic neurons in the basolateral amygdala participating in prenatal stress-induced anxiety. Methods Behavioral tests were used to explore the prenatal stress-induced anxiety behaviors of female adult mice. Real-time RT-PCR, western blot, chromatin immunoprecipitation, and electrophysiological analysis were employed to detect epigenetic changes of GABAergic system in the basolateral amygdala. Results Prenatal stress mice developed an anxiety-like phenotype accompanied by a significant increase of DNA methyltransferase 1 and a reduced expression of glutamic acid decarboxylase 67 in the basolateral amygdala. Prenatal stress mice also showed the increased binding of DNA methyltransferase 1 and methyl CpG binding protein 2 to glutamic acid decarboxylase 67 promoter region. The decrease of glutamic acid decarboxylase 67 transcript was paralleled by an enrichment of 5-methylcytosine in glutamic acid decarboxylase 67 promoter regions. Electrophysiological study revealed the increase of postsynaptic neuronal excitability in the cortical-basolateral amygdala synaptic transmission of prenatal stress mice. 5-Aza-deoxycytidine treatment restored the increased synaptic transmission and anxiety-like behaviors in prenatal stress mice via improving GABAergic system. Conclusion The above results suggest that DNA epigenetic modifications of GABAergic interneurons in the basolateral amygdala participate in the etiology of anxiety-like phenotype in prenatal stress mice. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate and compare the diagnostic performance of dynamic contrast‐enhanced (DCE)‐MRI, multiparametric MRI (mpMRI), and multimodality imaging (MMI) combining mpMRI and mammography (MG) for discriminating breast non‐mass‐like enhancement (NME) lesions. Methods: This retrospective study enrolled 193 patients with 199 lesions who underwent 3.0 T MRI and MG from January 2017 to December 2019. The features of DCE‐MRI, turbo inversion recovery magnitude (TIRM), and diffusion‐weighted imaging (DWI) were assessed by two breast radiologists. Then, all lesions were divided into microcalcification and non‐microcalcification groups to assess the features of MG. Comparisons were performed between groups using univariate analyses. Then, multivariate analyses were performed to construct diagnostic models for distinguishing NME lesions. Diagnostic performance was evaluated by using the area under the curve (AUC) and the differences between AUCs were evaluated by using the DeLong test. Results: Overall (n = 199), mpMRI outperformed DCE‐MRI alone (AUCmpMRI = 0.924 vs. AUCDCE-MRI = 0.884; p = 0.007). Furthermore, MMI outperformed both mpMRI and MG (the microcalcification group [n = 140]: AUCMMI = 0.997 vs. AUCmpMRI = 0.978, p = 0.018 and AUCMMI = 0.997 vs. AUCMG = 0.912, p < 0.001; the non‐microcalcification group [n = 59]: AUCMMI = 0.857 vs. AUCmpMRI = 0.768, p = 0.044 and AUCMMI = 0.857 vs. AUCMG = 0.759, p = 0.039). Conclusion & advances in knowledge: DCE‐MRI combined with DWI and TIRM information could improve the diagnostic performance for discriminating NME lesions compared with DCE‐MRI alone. Furthermore, MMI combining mpMRI and MG showed better discrimination than both mpMRI and MG. [ABSTRACT FROM AUTHOR]

OBJECTIVE We introduced a new atrial septum remodeling technique and further investigated the feasibility of this method in facilitating the intra-operative device closure (IODC) of multiple atrial septal defects (ASDs). METHODS Adult patients with multiple nearby ASDs, which were not eligible for transcatheter closure, were enrolled in this study. Transesophageal echocardiogram (TEE) was applied for intra-operative evaluation. The multiple ASDs were divided into three different types according to its morphology. Based on the concept of breaking the rim between multiple ASDs and making it feasible for single device closure, atrial septum remodeling procedure was carried out via pre-atrial approach using special clamp under the guidance of TEE. IODC was then attempted for reshaped ASD. Successful rate and perioperative complications were then noted. RESULTS Eleven patients were enrolled in this study, with mean age being 23.4 ± 5.3 years and mean weight 51.6 ± 8.0 kg. Among them, seven patients have double ASDs and four have triple ASDs. Mean diameter of isolated ASD was 10.4 ± 3.8 mm with a mean distance of 3.2 ± 1.2 mm between each other. Atrial septum remodeling procedure was successfully done in all patients. One device was then used for each patient. Mean ASD diameter after remodeling procedure was 20.6 ± 3.9 mm with mean device size 23.5 ± 4.0 mm. Complete closure of multiple ASDs was achieved in nine patients immediately after the procedure; two patients had trivial grade shunt after device deployment that resolved within the 3-month follow-up. No severe complications were noticed during the perioperative period and the 3-month follow-up. CONCLUSIONS Atrial septum remodeling technique seems to be a safe and effective method that could largely facilitate the successful IODC of multiple ASDs. [ABSTRACT FROM AUTHOR]