The effects of circFBXL5 on the malignant biological behaviors of bladder cancer T24 cells by targeting miR-515-5p and its molecular mechanisms / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨circFBXL5通过靶向miR-515-5p影响膀胱癌T24细胞的增殖、迁移、侵袭及其分子机制。方法： 收集2020年4月至2020年6月间在苏州市中西医结合医院手术切除的41例膀胱癌组织及其癌旁组织，采用qPCR法检测circFBXL5、miR-515-5p的表达；双荧光素酶报告实验验证circFBXL5与miR-515-5p之间的靶向关系，体外培养人膀胱癌T24细胞，实验分为si-NC组、si-circFBXL5组、anti-miR-NC+si-circFBXL5组和si-circFBXL5+anti-miR-515-5p组；MTT法、细胞克隆形成实验、FCM、Transwell实验和WB法分别检测转染后T24细胞的增殖、细胞克隆形成、迁移、侵袭和凋亡及BAX、Bcl-2蛋白水平。结果：膀胱癌组织中circFBXL5呈高表达，miR-515-5p呈低表达（均P<0.05）；circFBXL5靶向且负向调控miR-515-5p的表达；敲减circFBXL5后T24细胞的增殖抑制率、凋亡率和BAX蛋白水平均显著增高（均P<0.05），细胞克隆形成数和迁移、侵袭细胞数均显著减少（均P<0.05），Bcl-2蛋白水平显著降低（P<0.05）；同时敲减circFBXL5和miR-515-5p可部分逆转敲减circFBXL5对T24细胞增殖的抑制作用。结论：circFBXL5通过调控miR-515-5p表达影响膀胱癌T24细胞的增殖、迁移、侵袭，circFBXL5和miR-515-5p可能膀胱癌治疗的潜在分子靶标。

A Two-Fold Interpenetrated Dual-Emitting Luminescent Metal-Organic Framework as a Ratiometric Sensor for Chromium(III).

A novel two-fold interpenetrated metal-organic framework, namely Co-EDDA, was synthesized by hydrothermal reaction of 5,5'-[ethane-1,2-diylbis(oxy)]diisophthalic acid (H4EDDA), Co(NO3)2·6H2O, and 1,4-di(1H-imidazol-1-yl)benzene in water in an alkaline environment and structurally characterized. Co-EDDA could display clear dual-emission signals at 350 and 430 nm, representing the charge transfer emission between metal ions and the ligand and the ligand-based emission, respectively, which represents the ratiometric luminescence response to chromium(III) with high selectivity and sensitivity (limit of detection of 0.54 µM). Comprehensive studies indicate that the detection can be attributed to the interaction between the Cr3+ ions and the O atoms on the ether bond in Co-EDDA.

Left bundle branch pacing for cardiac resynchronization therapy: A systematic literature review and meta-analysis.

BACKGROUND: Left bundle branch pacing (LBBP) recently has been suggested as an alternative modality to deliver cardiac resynchronization therapy (CRT). Data on LBBP for CRT are limited to small sample reports, and clinical benefits and risks have not been systematically assessed. We sought to systematically examine published studies of LBBP for CRT and quantify the feasibility and efficacy of the therapy. METHODS: Cochrane Library, PubMed, Web of Science, and Embase databases were searched from inception to September 30, 2020 to identify relevant studies evaluating LBBP in patients for CRT. Clinical outcomes of interest included implant success rate, QRS duration (QRSd), pacing threshold, left ventricular (LV) function at baseline and follow-up, heart failure-related hospitalization, and mortality. Data were extracted and summarized. RESULTS: A total of six studies (two single-arm studies and four comparative studies) involving 174 patients were included. The results showed that the average age of patients was 64.9 years and all were implanted for CRT. The procedural success rate was only reported in two studies (97% and 81.1%, respectively). LBBP resulted in a narrow of mean QRSd from 172.7 ± 4.8 to 115.1 ± 7.6 ms. LV function, including LV ejection fraction and LV end-diastolic dimension improved at follow-up. During a mean follow-up of 8.1 months, 1.3% of patients experienced heart failure-related hospitalization and no patients died. CONCLUSION: LBBP is a feasible strategy with significant efficacy and safety for CRT candidates.

Impact of cardiovascular disease and cardiac injury on in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has produced a significant health burden worldwide, especially in patients with cardiovascular comorbidities. The aim of this systematic review and meta-analysis was to assess the impact of underlying cardiovascular comorbidities and acute cardiac injury on in-hospital mortality risk. METHODS: PubMed, Embase and Web of Science were searched for publications that reported the relationship of underlying cardiovascular disease (CVD), hypertension and myocardial injury with in-hospital fatal outcomes in patients with COVID-19. The ORs were extracted and pooled. Subgroup and sensitivity analyses were performed to explore the potential sources of heterogeneity. RESULTS: A total of 10 studies were enrolled in this meta-analysis, including eight studies for CVD, seven for hypertension and eight for acute cardiac injury. The presence of CVD and hypertension was associated with higher odds of in-hospital mortality (unadjusted OR 4.85, 95% CI 3.07 to 7.70; I2=29%; unadjusted OR 3.67, 95% CI 2.31 to 5.83; I2=57%, respectively). Acute cardiac injury was also associated with a higher unadjusted odds of 21.15 (95% CI 10.19 to 43.94; I2=71%). CONCLUSION: COVID-19 patients with underlying cardiovascular comorbidities, including CVD and hypertension, may face a greater risk of fatal outcomes. Acute cardiac injury may act as a marker of mortality risk. Given the unadjusted results of our meta-analysis, future research are warranted.

The predictive value of heart rate variability indices tested in early period after radiofrequency catheter ablation for the recurrence of atrial fibrillation.

INTRODUCTION: To explore the relationship between recurrence of atrial fibrillation (AF) and the autonomic nervous activity evaluated by heart rate variability (HRV) indices after radiofrequency catheter ablation (RFCA) in the early period. METHODS: We enrolled 102 patients with paroxysmal AF and tested the HRV indices by the high-resolution Holter electrocardiogram the next morning after RFCA. The HRV indices were compared between the non-recurrence group (n = 85) and the recurrence group (n = 17). RESULTS: The HRV indices included standard deviation of normal to normal intervals (SDNN), SDNN index, root-mean square successive differences (RMSSD), the proportion of normal to normal intervals differing by >50 millisecond (ms) (pNN50), high-frequency components (HF), low-frequency components (LF) and very low-frequency components were significantly higher in recurrence group than that in non-recurrence group, while no such difference was found for LF/HF. Based on the median value of the recurrent time (9 months), RMSSD (P = .012), pNN50 (P < .0001) and HF (P = .033) were lower in late recurrence group than that in early recurrence group. The Cox regression analyses indicated that higher values of RMSSD (P = .01), pNN50 (P = .02) and HF (P = .02) were associated with a higher risk of recurrence after adjusted for covariates. The receiver operating characteristic curves showed higher rates of clinical recurrence of AF after RFCA in patients with RMSSD ≥27.5 ms, pNN50 ≥4.5%, and HF ≥178.25 ms2 . CONCLUSIONS: Values of RMSSD, pNN50, and HF tested in the early period after RFCA could independently predict the recurrence of AF.

Genetically Elevated Serum Uric Acid and Renal Function in an Apparently Healthy Population.

BACKGROUND: The association between uric acid and kidney disease has been extensively investigated. Numerous studies have reported the association between circulating levels of uric acid and renal function. OBJECTIVES: To test, by the Mendelian randomization method, whether there is a causal association between circulating levels of uric acid and renal function. METHODS: In 989 participants, estimated glomerular filtration rate (eGFR) was calculated, the circulating level of uric acid was tested, and the uric acid polymorphism (rs11722228) was genotyped. RESULTS: After adjusting for age, gender, smoking history, alcohol intake, antihypertensive medication, body mass index, waist-to-hip ratio, and levels of urea nitrogen and creatinine, a significant allelic difference was found in uric acid levels for each genotype (p < 0.0001). Furthermore, the circulating levels of uric acid were negatively associated with eGFR after adjusting for cardiovascular risk factors and other potential confounders (p < 0.0001). Meanwhile, eGFR was significantly associated with the genotypes of rs11722228 (ß = -0.07; p = 0.02). CONCLUSIONS: Evidence from the Mendelian randomization approach implied a causal relationship between uric acid and renal function in an apparently healthy population.

Association of CYBA rs7195830 polymorphism with estimated glomerular filtration rate in an adult Han sample from Jiangsu province, China.

BACKGROUND: Reactive oxygen species are thought to contribute to the development of renal damage. The P22phox subunit of nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase, encoded by the cytochrome b245a polypeptide gene, CYBA, plays a key role in superoxide anion production. We investigated the association of CYBA rs7195830 polymorphism with estimated glomerular filtration rate (eGFR) and the role it plays in the pathogenesis of chronic kidney disease (CKD) in a Han Chinese sample. METHODS: The Gaoyou study enrolled 4473 participants. Serum levels of creatinine were measured and eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equations. The CYBA polymorphisms were genotyped. Then we investigated the association between eGFR and the rs7195830 polymorphism in the recessive model. RESULTS: The AA genotype of rs7195830 was associated with significantly lower values of eGFR compared with the GG and AG genotypes ((102.76 ± 17.07) ml×min(-1)×1.73 m(-2) vs. (105.08 ± 16.30) ml×min(-1)± 1.73 m(-2)). The association remained significant in the recessive model after adjusting for age, gender, body mass index, smoking, hypertension, diabetes mellitus, uric acid, triglyceride, low density lipoprotein cholesterol and high density lipoprotein cholesterol (ß=1.666, P=0.031). The rs7195832 AA genotype was an independent risk factor for CKD: eGFR <60 ml×min(-1)×1.73 m(-2) (odds ratio=3.32; 95% CI=1.21-9.13). CONCLUSION: The AA genotype of rs7195830 is independently associated with lower estimated glomerular filtration rate and is significantly associated with CKD.

Physical activity modifies the association between CYBA gene polymorphisms and small artery elasticity in a Chinese population.

Emerging evidence suggests that increased superoxide production is responsible for a significant proportion of endothelial dysfunction. The relationship between variants of the CYBA gene and cardiovascular diseases is currently debated. In the present study, we investigated the influence of CYBA polymorphisms (rs1049255 and rs7195830) on arterial elasticity in a Chinese population. In the 2178 participants enrolled in the GaoYou study, we measured large artery elasticity (C1) and small artery elasticity (C2) non-invasively, genotyped the CYBA polymorphisms and calculated energy expenditure. The AA genotype of the rs1049255 polymorphism was associated with a lower C2 than were the GG/AG genotypes (5.31±0.11 vs. 5.52±0.06 ml mm Hg(-1) × 100; P=0.01). Further analyses revealed an interaction between CYBA polymorphisms and physical activity with respect to C2 (P=0.007 for rs1049255 and P=0.038 for rs7195830). In less physically active participants, the AA genotype of the rs1049255 polymorphism was associated with a significantly lower C2 than the GG/AG genotypes (4.69±0.16 vs. 5.26±0.19 ml mm Hg(-1) × 100; P=0.008). In physically active participants, the GG/AG genotypes of rs7195830 polymorphism were correlated with higher C2 values than the AA genotype (5.84±0.08 vs. 5.08±0.32 ml mm Hg(-1) × 100; P=0.049). Haplotype analyses revealed higher C2 values in rs1049255G-rs7195830G carriers (P=0.0015). In conclusion, the rs1049255 and rs7195830 polymorphisms of the CYBA gene were associated with C2 in a Chinese population; physical activity could modify this genetic effect.

[Relationship between high-sensitive c-reactive and blood pressure].

OBJECTIVE: To investigate the relationship between c-reactive protein (CRP) and blood pressure in a general population. METHODS: We randomly selected 3889 subjects aged 18 - 74 years stratified by gender and age in Baqiao, a rural area of Jiangsu Province. A standardized questionnaire was used to collect information on medical history, smoking, alcohol intake and use of medications. Blood pressure was measured by mercury sphygmomanometer. Serum CRP (hCRP) concentration was measured using a high sensitivity BNprosec immunonephelometric assay. Subjects were divided into 4 groups according to their interquartile range of CRP levers: group Q1 (men hCRP < 2.04 mg/L; women hCRP < 1.80 mg/L); group Q2 (men 2.04 mg/L ≤ hCRP < 3.01 mg/L; women 1.80 mg/L ≤ hCRP < 2.76 mg/L); group Q3 (men 3.01 mg/L ≤ hCRP < 4.14 mg/L; women 2.76 mg/L ≤ hCRP < 3.84 mg/L); and group Q4 (men 4.14 mg/L ≤ hCRP; women 3.84 mg/L ≤ hCRP). RESULTS: Systolic blood pressure (SBP, adjusted P = 0.016) and pulse pressure (PP, adjusted P = 0.003) of men and PP (adjusted P = 0.002) of women were increased in proportion to increased CRP levels. Diastolic blood pressure was not associated with CRP levels. Multiple stepwise regression analysis showed that logCRP was independently associated with SBP and PP in men and PP in women. hCRP was independently associated with hypertension in men. Compared with group Q1, male people in group Q4 faced a 40.4% (95% confidence interval: 4.9% - 87.9%) higher risk of hypertension. CONCLUSIONS: hCRP was independently associated with PP in men and women, and SBP in men. hCRP was independently associated with hypertension in men but not in women in this study population.