A nomogram for predicting 28-day mortality in elderly patients with acute kidney injury receiving continuous renal replacement therapy: a secondary analysis based on a retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and serious condition, particularly among elderly patients. It is associated with high morbidity and mortality rates, further compounded by the need for continuous renal replacement therapy in severe cases. To improve clinical decision-making and patient management, there is a need for accurate prediction models that can identify patients at a high risk of mortality. METHODS: Data were extracted from the Dryad Digital Repository. Multivariate analysis was performed using least absolute shrinkage and selection operator (LASSO) logistic regression analysis to identify independent risk factors and construct a predictive nomogram for mortality within 28 days after continuous renal replacement therapy in elderly patients with acute kidney injury. The discrimination of the model was evaluated in the validation cohort using the area under the receiver operating characteristic curve (AUC), and calibration was evaluated using a calibration curve. The clinical utility of the model was assessed using decision curve analysis (DCA). RESULTS: A total of 606 participants were enrolled and randomly divided into two groups: a training cohort (n = 424) and a validation cohort (n = 182) in a 7:3 proportion. A risk prediction model was developed to identify independent predictors of 28-day mortality in elderly patients with AKI. The predictors included age, systolic blood pressure, creatinine, albumin, phosphorus, age-adjusted Charlson Comorbidity Index (CCI), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score. These predictors were incorporated into a logistic model and presented in a user-friendly nomogram. In the validation cohort, the model demonstrated good predictive performance with an AUC of 0.799. The calibration curve showed that the model was well calibrated. Additionally, DCA revealed significant net benefits of the nomogram for clinical application. CONCLUSION: The development of a nomogram for predicting 28-day mortality in elderly patients with AKI receiving continuous renal replacement therapy has the potential to improve prognostic accuracy and assist in clinical decision-making.

A hybrid attention network with convolutional neural network and transformer for underwater image restoration.

The analysis and communication of underwater images are often impeded by various elements such as blur, color cast, and noise. Existing restoration methods only address specific degradation factors and struggle with complex degraded images. Furthermore, traditional convolutional neural network (CNN) based approaches may only restore local color while ignoring global features. The proposed hybrid attention network combining CNN and Transformer focuses on addressing these issues. CNN captures local features and the Transformer uses multi-head self-attention to model global relationships. The network also incorporates degraded channel attention and supervised attention mechanisms to refine relevant features and correlations. The proposed method fared better than existing methods in a variety of qualitative criteria when evaluated against the public EUVP dataset of underwater images.

The Nedd8-activating enzyme inhibitor MLN4924 suppresses colon cancer cell growth via triggering autophagy.

Neddylation is a post-translational protein modification process. MLN4924 is a newly discovered pharmaceutical neddylation inhibitor that suppresses cancer growth with several cancer types. In our study, we first investigated the effect of MLN4924 on colon cancer cells (HCT116 and HT29). MLN4924 significantly inhibited the neddylation of cullin-1 and colon cancer cell growth in a time and dose-dependent manner. MLN4924 induced G2/M cell cycle arrest and apoptosis in HCT116 and HT29 cells. Moreover, MLN4924 also triggered autophagy in HCT116 and HT29 cells via suppressing the PI3K/AKT/mTOR pathway. Inhibiting autophagy by autophagy inhibitor 3-MA or ATG5 knockdown reversed the function of MLN4924 in suppressing colon cancer cell growth and cell death. Interestingly, MLN4924 suppresses colon cell growth in a xenograft model. Together, our finding revealed that blocking neddylation is an attractive colon cancer therapy strategy, and autophagy might act as a novel anti-cancer mechanism for the treatment of colon cancer by MLN4924.

Mixed Aqueous Extract of Salvia Miltiorrhiza Reduces Blood Pressure through Inhibition of Vascular Remodelling and Oxidative Stress in Spontaneously Hypertensive Rats.

BACKGROUND/AIMS: Salvia miltiorrhiza (SM) contains four major aqueous active ingredients, which have been isolated, purified and identified as danshensu (DSS), salvianolic acid A (Sal-A), salvianolic acid B (Sal-B) and protocatechuic aldehyde (PAL), totally abbreviated as SABP. Although SM is often used to treat various cardiovascular diseases in traditional Chinese medicine, the efficacy and function of optimal compatibility ratio of SM's active ingredients (SABP) in the prevention and treatment of cardiovascular diseases remain uncertain. This study investigated antihypertensive effect and underlying mechanisms of SABP vs. SM lyophilized powder (SMLP) in spontaneously hypertensive rats (SHR) and to establish the ratio of the optimal compatibility of DSS, Sal-A, Sal-B and PAL in improving cardiovascular functions. METHODS: The SHRs were treated with either SABP or SMLP and their systolic blood pressures (SBP) were monitored. The isolated thoracic aorta of SHRs was segregated for immunohistochemistry, Hematoxylin-Eosin stain and mRNA and protein expression of NOX4, TGF-ß1, Col-I, ET-1, α-SMA and Smad7. Moreover, the adventitial fibroblasts (AFs) were isolated and cultured from SD rats' aorta and the reactive oxygen species (ROS) production was determined after SABP or SMLP treatment. RESULTS: SABP, but not SMLP, significantly reduced SBP, which were accompanied by the inhibited morphological changes in the thoracic aorta and the reduced mRNA and protein expression of NOX4, TGF-ß1, Col-I, ET-1 and α-SMA, but the increased Smad 7 expression in SHRs. Moreover, SABP also resulted in a decreased ROS production in AFs of SD rats. CONCLUSIONS: These results indicate that SABP, but not SMLP, treatment potently inhibits hypertension through improvements of vascular remodeling and oxidative stress. The present study provides new evidence that the efficacy and function from optimal compatibility ratio of SM active ingredients is much better than its lyophilized powder, which represents a strategy to develop SM's new beneficial effect in improving cardiovascular functions.

Adjunctive loading dose of cilostazol in preventing periprocedural myocardial infarction.

INTRODUCTION: Periprocedural myocardial infarction (PMI) is a common complication of percutaneous coronary intervention (PCI). This study evaluated the safety and efficacy of adjunctive loading dose of cilostazol in preventing PMI in patients with acute coronary syndrome (ACS). METHODS: A total of 113 patients with ACS undergoing PCI were randomized to receive loading doses of dual (aspirin plus clopidogrel; DAPT group; n=57) or triple antiplatelet therapy (aspirin plus clopidogrel plus cilostazol; TAPT group; n=56). The loading and maintenance doses were 100 and 50 mg bid for cilostazol. Patients in the TAPT group received adjunctive cilostazol for 1 week. Cardiac biomarkers were measured before PCI, 8 and 24 hours after PCI to determine the incidence of PMI. RESULTS: There was no significant difference in the incidence of PMI between the TAPT and DAPT groups (32.1% vs 47.4%, P=.098). However, in the antiplatelet-naïve subgroup, TAPT significantly lowered the incidence of PMI compared to DAPT (17.9% vs 42.9%, P=.042). In the antiplatelet-treated subgroup, the incidences of PMI were comparable (46.4% vs 51.7%, P=.698). Multivariable logistic analysis showed that antiplatelet-treated (vs antiplatelet-naïve) (hazard ratio [HR]: 2.45; 95% confidence interval [CI]: 1.09-5.52; P=.030) subgroup was independently associated with PMI. However, TAPT (vs DAPT) (HR: 0.51; 95% CI: 0.23-1.14; P=.102) was not an independent protective factor of PMI. CONCLUSIONS: The present single-center, randomized study indicates that TAPT with adjunctive cilostazol was not associated with lower incidence of PCI-related PMI in patients with ACS. Further study with large study population is needed to get definite conclusions.

Cardioprotective effects of traditional Chinese medicine Guanmaitong on acute myocardial infarction.

Guanmaitong (GMT) is a traditional Chinese herbal compound that has been used for the treatment of coronary heart disease (CHD) and other cardiovascular diseases. However, the efficacy of GMT in treating cardiovascular diseases remains unclear. The aim of the present study was to investigate the protective mechanisms and identify the targeted proteins and signaling networks associated with the physiological activity of GMT in a rat model of acute myocardial infarction (AMI). Sprague-Dawley rats were randomly allocated into five groups: Control group (sham-operated), the model group, and small, medium, and large dosage GMT groups. The rat model of AMI was established via ligation of the coronary artery. The results indicate that GMT was able to reduce myocardial infarction size and improve the activities of tumor necrosis factor-α (TNF-α), intercellular adhesion molecule 1 (ICAM-1) and interleukin-1. Furthermore, the reduced apoptotic index of the GMT-treated cardiocytes (P<0.05 vs. model group) was in accordance with the downregulated expression of Bax and the upregulated expression of Bcl-2. In conclusion, GMT may exert a protective potential against myocardial infarction injury by inhibiting apoptosis and inflammation of cardiomyocytes, and may offer a promising adjunct treatment for CHD.

Characterization and functions of vascular adventitial fibroblast subpopulations.

BACKGROUND: Adventitial fibroblasts have been shown to play an important role in vascular remodeling and contribute to neointimal formation in vascular diseases. However, little is known about adventitial fibroblast subpopulations. This study explored the process of isolating rat thoracic aorta adventitial fibroblast subpopulations and characterized their properties following stimulation with angiotensin II (ANG II), a critical factor involved in cardiovascular diseases such as hypertension. METHODS: Adventitial fibroblasts were isolated and cultured from rat aorta. Fibroblast subpopulations were individually expanded using cloning ring techniques. Cells were treated with ANG II (10 nM, 100 nM and 1 µM) for 0.5, 1, 1.5, 3, 6, 12, or 24 h, and ANG II-induced proliferation and migration were measured by MTT assay and Transwell. Cells were treated with ANG II (100 nM) in the presence or absence of ANG II receptor antagonists (100 µM), losartan (for AT1) and PD-123319 (for AT2). PreproET-1 mRNA and ET-1 were determined by RT-PCR and ELISA, respectively. Collagen type I was detected by western blotting. RESULTS: Two major fibroblast subpopulations were found in the adventitia, epithelioid-like cells and spindle-like cells; Although ANG II promotes the growth of both subpopulations, epithelioid-like cell proliferation shows dose-dependency on ANG II from 10 nM to 1 µM, while proliferation of spindle-like cells reaches a peak value following 100 nM ANG II stimulation; ANG II stimulation enhanced epithelioid-like but not spindle-like cell migration; ANG II dose-dependently increased the expression of preproET-1 and collagen type I, and enhanced ET-1 secretion in epithelioid-like but not spindle-like cells, effects abolished by the AT1 receptor antagonist, but not with AT2 receptor antagonist. CONCLUSION: Adventitial fibroblasts are heterogeneous and epithelioid-like subpopulations with high sensitivity to ANG II stimulation may be implicated in the pathophysiological mechanisms of vascular remodeling, reparative processes and cardiovascular diseases.

Milk and dairy consumption and risk of bladder cancer: a meta-analysis.

OBJECTIVE: To explore potential relations between the intake of milk or dairy products and the risk of bladder cancer. METHODS: Eligible studies published up to May 2011 were retrieved via both computer searches and manual review of references. Random-effects models were used to calculate summary relative risk estimates (SRRE) based on high-contrast to low-intake values. Sensitivity and influence analyses were conducted, and heterogeneity among study results was explored through stratified analyses by study design, gender, geographic region, year of publication, or whether or not adjustment for several confounders (ie, age, gender, body mass index, smoking, and total energy intake). RESULTS: We extracted data from 14 studies on milk (involving 4879 cases) and 6 studies on dairy products (3087 cases). The total study population was up to 324,241 individuals. Overall, there was no significant association between milk intake and bladder cancer (SRRE 0.89, 95% CI 0.77-1.02). However, an inverse association was found in the United States (SRRE 0.88, 95% CI .79-.99). In addition, no significant association was observed between consumption of dairy products and risk of bladder cancer (SRRE 0.95, 95% CI .71-1.27), though an inverse association was detected in the Japanese population (SRRE 0.56, 95% CI .40-.80). CONCLUSION: There appears to be enough evidence to support the null hypothesis. The overall result was not statistically significant. The findings of this meta-analysis are not supportive of an independent relationship between the intake of milk or dairy products and the risk of bladder cancer. However, these findings are based on limited research. Further efforts should be made to confirm these findings.

[Effects and potential mechanisms of short-term use of simvastatin on myocardial no-reflow after ischemia-reperfusion in rats].

OBJECTIVE: The main objective of this study is to assess the the effect of simvastatin (sim) on myocardial no-reflow (NR) and explore the possible potential mechanisms. METHODS: Adult male Wistar rats were randomized into sham group (n = 12), I/R (90 min ischemia via coronary ligation/120 min reperfusion, n = 18) and I/R plus sim group (20 mgxkg(-1)xd(-1) sim pretreated via gavage beginning 3 days before I/R, n = 18). After reperfusion, area at risk/area of left ventricular (RA/LVA), area of NR, determined by the area not perfused by thioflavin-S/area at risk (NA/RA) and area of myocardial infarction/area at risk (MIA/RA) were measured. Myocardium homogenate was used to determine the activity of eNOS, iNOS and MPO, and the content of NO and MDA. Myocardial immunohistochemistry was performed to determine the positive index of NF-kappaB p65 in cardiomyocytes and arteriole. RESULTS: The NR and myocardial infarction areas in I/R plus sim group were significantly smaller than those in I/R group (34.10 +/- 7.05 vs. 52.09 +/- 6.89, 78.80 +/- 7.60 vs. 90.13 +/- 5.72, each P < 0.05) while the ischemia area was similar between the 2 groups (P > 0.05). The myocardial activities of iNOS and MPO, the contents of NO and MDA were significantly lower while eNOS activity was significantly higher in I/R plus sim group than those in I/R group (5.02 +/- 1.64 vs. 9.19 +/- 2.89, 586.21 +/- 126.97 vs. 744.49 +/- 137.53, 257.72 +/- 93.43 vs. 384.10 +/- 40.68, 72.10 +/- 18.56 vs. 111.84 +/- 38.58, 7.08 +/- 1.74 vs. 3.72 +/- 0.98, all P < 0.05). The positive index of NF-kappaB p65 in cardiocytes and arteriole at left ventricular wall near the area of myocardial infarction was significantly lower in I/R plus sim group than that in I/R group (21.59 +/- 10.5 vs. 34.32 +/- 9.55, 27.27 +/- 13.19 vs. 44.91 +/- 15.06, each P < 0.05). CONCLUSION: Simvastatin could improve myocardial NR after ischemia-reperfusion by attenuating endothelial dysfunction and inhibiting inflammation and neutrophil activation.