The Specificity and Accuracy of Echocardiography in Diagnosing Acute Heart Failure: A Systematic Review and Meta-Analysis.

Objective: This meta-analysis evaluates the diagnostic value of echocardiography for Acute Heart Failure (AHF) and its utility in urgent clinical situations, emphasizing its significance for accurate and timely diagnosis in critical care. Methods: Relevant studies from databases like PubMed and Embase were selected using terms such as 'Ultrasound' and 'acute heart failure'. Inclusion criteria focused on studies evaluating echocardiographic diagnosis in adult patients presenting with symptoms suggestive of AHF. Quality assessment was performed using RevMan 5.3 and QUADAS. Key metrics like sensitivity, specificity, and likelihood ratios were analyzed using STATA 15.1. The types of echocardiography assessed included transthoracic and focused cardiac ultrasound. Results: Eighteen articles were included, indicating echocardiography's high sensitivity (0.92) and specificity (0.96) in diagnosing AHF. The combined positive likelihood ratio of 23.2 suggests that patients with AHF are over 23 times more likely to have a positive echocardiography result than those without AHF, greatly influencing clinical decision-making toward confirming the diagnosis. The AUC of the SROC curve was 0.98, indicating excellent overall accuracy. Conclusion: Echocardiography is highly accurate in diagnosing AHF, underscored by its critical role in early treatment decisions and potential integration into standard care protocols, thereby preventing adverse outcomes and improving patient management.

Protective effect of melatonin against metabolic disorders and neuropsychiatric injuries in type 2 diabetes mellitus mice.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by hyperglycemia and progressive cognitive dysfunction, and our clinical investigation revealed that the plasma concentration of melatonin (Mlt) decreased and was closely related to cognition in T2DM patients. However, although many studies have suggested that Mlt has a certain protective effect on glucose and lipid metabolism disorders and neuropsychiatric injury, the underlying mechanism of Mlt against T2DM-related metabolic and cognitive impairments remains unclear. PURPOSE: The aim of the present study was to investigate the therapeutic effect of Mlt on metabolic disorders and Alzheimer's disease (AD)-like neuropsychiatric injuries in T2DM mice and to explore the possible underlying molecular mechanism involved. METHODS: A T2DM mouse model was established by a combination of a high-fat diet (HFD) and streptozotocin (STZ, 100 mg/kg, i.p.), and Mlt (5, 10 or 20 mg/kg) was intragastrically administered for six consecutive weeks. The serum levels of glycolipid metabolism indicators were measured, behavioral performance was tested, and the protein expression of key molecules involved in the regulation of synaptic plasticity, circadian rhythms, and neuroinflammation in the hippocampus was detected. Moreover, the fluorescence intensities of glial fibrillary acidic protein (GFAP), ionized calcium binding adapter molecule 1 (IBA-1), amyloid ß-protein (Aß) and phosphorylated Tau (p-Tau) in the hippocampus were also observed. RESULTS: Treatment with Mlt not only improved T2DM-related metabolic disorders, as indicated by increased serum concentrations of fasting blood glucose (FBG), glycosylated hemoglobin (HbAlc), insulin (INS), total cholesterol (TC) and triglyceride (TG), improved glucose tolerance and liver and pancreas function but also alleviated AD-like neuropsychiatric injuries in a HFD/STZ-induced mouse model, as indicated by decreased immobility time in the tail suspension test (TST) and forced swimming test (FST), increased preference indices of novel objects or novel arms in the novel object recognition test (NOR) and Y-maze test (Y-maze), and improved platform positioning capability in the Morris water maze (MWM) test. Moreover, treatment with Mlt also improved the hyperactivation of astrocytes and microglia in the hippocampus of mice, accompanied by reduced expression of interleukin 1ß (IL-1ß), interleukin 6 (IL-6), tumor necrosis factor (TNF-α), Aß, and p-Tau and increased expression of brain-derived neurotrophic factor (BDNF), Synapsin I, Synaptotagmin I, melatonin receptor 1B (MT1B), brain muscle arnt-like protein 1 (Bmal1), circadian locomotor output cycles kaput (Clock), period 2 (Per2), and cryptochrome 2 (Cry2). CONCLUSION: Mlt alleviated T2DM-related metabolic disorders and AD-like neuropsychiatric injuries in a HFD/STZ-induced mouse model, possibly through a mechanism involving the regulation of glial activation and associated neuroinflammation and the balancing of synaptic plasticity and circadian rhythms in the hippocampus.

MiR-1909-5p targeting GPX4 affects the progression of aortic dissection by modulating nicotine-induced ferroptosis.

OBJECTIVE: Aortic dissection (AD) is a prevalent and acute clinical catastrophe characterized by abrupt manifestation, swift progression, and elevated fatality rates. Despite smoking being a significant risk factor for AD, the precise pathological process remains elusive. This investigation endeavors to explore the mechanisms by which smoking accelerates AD through ferroptosis induction. METHODOLOGY: In this novel study, we detected considerable endothelial cell death by ferroptosis within the aortic inner lining of both human AD patients with a smoking history and murine AD models induced by ß-aminopropionitrile, angiotensin II, and nicotine. Utilizing bioinformatic approaches, we identified microRNAs regulating the expression of the ferroptosis inhibitor Glutathione peroxidase 4 (GPX4). Nicotine's impact on ferroptosis was further assessed in human umbilical vein endothelial cells (HUVECs) through modulation of miR-1909-5p. Additionally, the therapeutic potential of miR-1909-5p antagomir was evaluated in vivo in nicotine-exposed AD mice. FINDINGS: Our results indicate a predominance of ferroptosis over apoptosis, pyroptosis, and necroptosis in the aortas of AD patients who smoke. Nicotine exposure instigated ferroptosis in HUVECs, where the miR-1909-5p/GPX4 axis was implicated. Modulation of miR-1909-5p in these cells revealed its regulatory role over GPX4 levels and subsequent endothelial ferroptosis. In vivo, miR-1909-5p suppression reduced ferroptosis and mitigated AD progression in the murine model. CONCLUSIONS: Our data underscore the involvement of the miR-1909-5p/GPX4 axis in the pathogenesis of nicotine-induced endothelial ferroptosis in AD.

Radiotherapy Resistance of 3D Bioprinted Glioma via ITGA2/p-AKT Signaling Pathway.

Due to the inherent radiation tolerance, patients who suffered from glioma frequently encounter tumor recurrence and malignant progression within the radiation target area, ultimately succumbing to treatment ineffectiveness. The precise mechanism underlying radiation tolerance remains elusive due to the dearth of in vitro models and the limitations associated with animal models. Therefore, a bioprinted glioma model is engineered, characterized the phenotypic traits in vitro, and the radiation tolerance compared to 2D ones when subjected to X-ray radiation is assessed. By comparing the differential gene expression profiles between the 2D and 3D glioma model, identify functional genes, and analyze distinctions in gene expression patterns. Results showed that 3D glioma models exhibited substantial alterations in the expression of genes associated with the stromal microenvironment, notably a significant increase in the radiation tolerance gene ITGA2 (integrin subunit A2). In 3D glioma models, the knockdown of ITGA2 via shRNA resulted in reduced radiation tolerance in glioma cells and concomitant inhibition of the p-AKT pathway. Overall, 3D bioprinted glioma model faithfully recapitulates the in vivo tumor microenvironment (TME) and exhibits enhanced resistance to radiation, mediated through the ITGA2/p-AKT pathway. This model represents a superior in vitro platform for investigating glioma radiotherapy tolerance.

CT radiomics nomogram for prediction of the Ki-67 index in head and neck squamous cell carcinoma.

OBJECTIVES: To construct and validate a contrast-enhanced computed tomography (CECT)-based radiomics nomogram to predict Ki-67 expression level in head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 217 patients with HNSCC who underwent CECT scans and immunohistochemical examination of their Ki-67 index were enrolled in this study. The patients were divided into a training set (n = 140; Ki-67: ≥ 50% [n = 72] and < 50% [n = 68]) and an external test set (n = 77; Ki-67: ≥ 50% [n = 38] and < 50% [n = 39]). The least absolute shrinkage and selection operator method was used to select key features for a CECT-image-based radiomics signature and a radiomics score (Rad-score) was calculated. A clinical model was established using clinical data and CT findings. The independent clinical factors and Rad-score were then combined to construct a radiomics nomogram. The performance characteristics of the Rad-score, clinical model, and nomogram were assessed using ROCs and decision curve analysis. RESULTS: Twenty features were finally selected to construct the Rad-score. The radiomics nomogram incorporating the Rad-score, low histological grade, and lymphatic spread showed higher predictive value for the Ki-67 index (≥ 50% vs. < 50%) than the clinical model on both the training (AUC, 0.919 vs. 0.648, p < 0.001) and test (AUC, 0.832 vs. 0.685, p = 0.030) sets. Decision curve analysis demonstrated that the radiomics nomogram was more clinically useful than the clinical model. CONCLUSIONS: A CECT-based radiomics nomogram was constructed to predict the expression of Ki-67 in HNSCC. This model showed favorable predictive efficacy and might be useful for prognostic evaluation and clinical decision-making in patients with HNSCC. KEY POINTS: • Accurate pre-treatment prediction of Ki-67 index in HNSCC is crucial. • A CECT-based radiomics nomogram showed favorable predictive efficacy in estimation of Ki-67 expression status in HNSCC patients.

5'-tiRNA-Cys-GCA regulates VSMC proliferation and phenotypic transition by targeting STAT4 in aortic dissection.

Accumulating evidence shows that tRNA-derived fragments are a novel class of functional small non-coding RNA; however, their roles in aortic dissection (AD) are still unknown. In this study, we found that 5'-tiRNA-Cys-GCA was significantly downregulated in human and mouse models of aortic dissection. The abnormal proliferation, migration, and phenotypic transition of vascular smooth muscle cells (VSMCs) played a crucial role in the initiation and progression of aortic dissection, with 5'-tiRNA-Cys-GCA as a potential phenotypic switching regulator, because its overexpression inhibited the proliferation and migration of VSMCs and increased the expression of contractile markers. In addition, we verified that signal transducer and activator of transcription 4 (STAT4) was a direct downstream target of 5'-tiRNA-Cys-GCA. We found that the STAT4 upregulation in oxidized low-density lipoprotein (ox-LDL)-treated VSMCs, which promoted cell proliferation, migration, and phenotypic transformation, was reversed by 5'-tiRNA-Cys-GCA. Furthermore, 5'-tiRNA-Cys-GCA treatment reduced the incidence and prevented the malignant process of angiotensin II- and ß-aminopropionitrile-induced AD in mice. In conclusion, our findings reveal that 5'-tiRNA-Cys-GCA is a potential regulator of the AD pathological process via the STAT4 signaling pathway, providing a novel clinical target for the development of future treatment strategies for aortic dissection.

Identification of transfer RNA-derived fragments and their potential roles in aortic dissection.

Emerging evidence suggests that majority of the transfer RNA (tRNA)-derived small RNA, including tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs), play a significant role in the molecular mechanisms underlying some human diseases. However, expression of tRFs/tiRNAs and their potential roles in aortic dissection (AD) remain unclear. This study examined the expression characteristics and explored the functional roles of tRFs/tiRNAs in AD using RNA-sequencing, bioinformatics, real-time quantitative reverse transcription polymerase chain reaction, and loss- and gain-of-function analysis. Results revealed that a total of 41 tRFs/tiRNAs were dysregulated in the AD group compared to the control group. Among them, 12 were upregulated and 29 were downregulated (fold change≥1.5 and p < 0.05). RT-qPCR results revealed that expressions of tRF-1:30-chrM.Met-CAT was significantly upregulated, while that of tRF-54:71-chrM.Trp-TCA and tRF-1:32-chrM.Cys-GCA were notably downregulated; expression patterns were consistent with the RNA sequencing data. Bioinformatic analysis showed that a variety of related pathways might be involved in the pathogenesis of AD. Functionally, tRF-1:30-chrM.Met-CAT could facilitate proliferation, migration, and phenotype switching in vascular smooth muscle cells (VSMCs), which might serve as a significant regulator in the progression of AD. In summary, the study illustrated that tRFs/tiRNAs expressed in AD tissues have potential biological functions and may act as promising biomarkers or therapeutic targets for AD.

tsRNAs: Novel small molecules from cell function and regulatory mechanism to therapeutic targets.

tsRNAs are small fragments of RNAs with specific lengths that are generated by particular ribonucleases, such as dicer and angiogenin (ANG), clipping on the rings of transfer RNAs (tRNAs) in specific cells and tissues under specific conditions. Depending on where the splicing site is, tsRNAs can be segmented into two main types, tRNA-derived stress-induced RNAs (tiRNAs) and tRNA-derived fragments (tRFs). Many studies have shown that tsRNAs are functional molecules, not the random degradative products of tRNAs. Notably, due to their regulatory mechanism in regulating mRNA stability, transcription, ribosomal RNA (rRNA) synthesis and RNA reverse transcription, tsRNAs are significantly involved in the cell function, such as cell proliferation, migration, cycle and apoptosis, as well as the occurrence and development of a variety of diseases. In addition, tsRNAs may represent a new generation of clinical biomarkers or therapeutic targets because of their stable structures, high conservation and widely distribution, particularly in the peripheral tissues, bodily fluids and exosomes. In this review, we describe the generation, function and mechanism of tsRNAs and illustrate the current research progress of tsRNAs in various diseases, highlight their potentials as biomarkers and therapeutic targets in clinical application. Although our understanding of tsRNAs is still in infancy, the application prospects shown in this field deserve further exploration.

High-resolution MRI assessment of optic nerve sheath diameter in adults: optic nerve sheath variation and a new diagnostic tool for intracranial hypertension.

BACKGROUND: Assessment of optic nerve sheath diameter (ONSD) is a non-invasive measure of intracranial pressure (ICP). However, it is not clear whether healthy individuals exhibit ONSD variation or whether factors other than ICP affect the ONSD. PURPOSE: To investigate whether ONSD was correlated with age, sex, height, weight, eyeball transverse diameter (ETD), or body mass index (BMI), and to develop a new diagnostic model to increase the diagnostic accuracy of intracranial hypertension (IH). MATERIAL AND METHODS: A total of 145 relatively healthy adults and 40 patients with acute IH who underwent high-resolution magnetic resonance imaging (MRI) were enrolled in this study. Linear regression analyses were used to determine the relationship between ONSD and these variables. If correlations were identified, an index ONSDΔ removing variables effects was calculated. ROC analysis was used to assess the IH predictive value of ONSDΔ in terms of sensitivity and specificity. RESULTS: In relatively healthy adults, there was a correlation between ONSD and BMI (P = 0.002), which can be presented as an index ONSDΔ. The ONSDΔ model better predicted IH than the ONSD model (P = 0.035), with a sensitivity of 70.00%, a specificity of 71.72%, and an AUC of 0.755. CONCLUSION: A correlation between ONSD and body mass index (BMI) was found using high-resolution MRI. This result indicates that the effects of BMI should be considered along with the ONSD during ICP monitoring. Meanwhile, the index ONSDΔ was better than the ONSD in predicting IH and could be used to obtain a more precise estimation of ICP.

A CT-based radiomics nomogram for differentiation of lympho-associated benign and malignant lesions of the parotid gland.

OBJECTIVES: Preoperative differentiation between benign lymphoepithelial lesion (BLEL) and mucosa-associated lymphoid tissue lymphoma (MALToma) in the parotid gland is important for treatment decisions. The purpose of this study was to develop and validate a CT-based radiomics nomogram combining radiomics signature and clinical factors for the preoperative differentiation of BLEL from MALToma in the parotid gland. METHODS: A total of 101 patients with BLEL (n = 46) or MALToma (n = 55) were divided into a training set (n = 70) and validation set (n = 31). Radiomics features were extracted from non-contrast CT images, a radiomics signature was constructed, and a radiomics score (Rad-score) was calculated. Demographics and CT findings were assessed to build a clinical factor model. A radiomics nomogram combining the Rad-score and independent clinical factors was constructed using multivariate logistic regression analysis. The performance levels of the nomogram, radiomics signature, and clinical model were evaluated and validated on the training and validation datasets, and then compared among the three models. RESULTS: Seven features were used to build the radiomics signature. The radiomics nomogram incorporating the clinical factors and radiomics signature showed favorable predictive value for differentiating parotid BLEL from MALToma, with AUCs of 0.983 and 0.950 for the training set and validation set, respectively. Decision curve analysis showed that the nomogram outperformed the clinical factor model in terms of clinical usefulness. CONCLUSIONS: The CT-based radiomics nomogram incorporating the Rad-score and clinical factors showed favorable predictive efficacy for differentiating BLEL from MALToma in the parotid gland, and may help in the clinical decision-making process. KEY POINTS: • Differential diagnosis between BLEL and MALToma in parotid gland is rather difficult by conventional imaging modalities. • A radiomics nomogram integrated with the radiomics signature, demographics, and CT findings facilitates differentiation of BLEL from MALToma with improved diagnostic efficacy.

Comparison of postoperative outcomes following multidetector computed tomography based vs transesophageal echocardiography based annulus sizing for transcatheter aortic valve replacement: A systematic review and meta-analysis.

BACKGROUND: The purpose of this paper was to evaluate the difference in postoperative outcomes following multidetector computed tomography (MDCT) and transesophageal echocardiography (TEE)-based annulus sizing for transcatheter aortic valve replacement (TAVR). METHODS: Electronic search of PubMed, Biomed Central, Scopus, and Google Scholar databases was conducted until August 15, 2019. We included all types of studies comparing MDCT-based annulus sizing with TEE-based annulus sizing and assessing paravalvular regurgitation (PVR). Data were summarized using the Mantel-Haenszel odds ratio (OR) with 95% confidence intervals (CI). RESULTS: A total of six studies were included. Pooled analysis of 431 participants in the MDCT group and 509 participants in the TEE group demonstrated that MDCT-based annulus sizing is associated with a significantly lower incidence of more than moderate PVR as compared to 2DTEE-based sizing (OR: 0.31, 95% CI: 0.18-0.54, P < .0001; I2  = 0%). There was no statistical difference in annulus rupture (OR: 0.57, 95% CI: 0.12-2.66, P = .91; I2  = 0%), procedural mortality (OR: 0.97, 95% CI: 0.19-4.86, P = .97; I2  = 0%), and 30-day mortality (OR: 0.63, 95% CI: 0.26-1.50, P = .29; I2  = 0%) with MDCT or 2DTEE-based annulus sizing. Compared with 3DTEE, the incidence of PVR in the MDCT group was lower, but there was no statistical difference in 30-day mortality. CONCLUSION: Use of MDCT in comparison with 2DTEE is associated with significantly lower incidence of more than moderate PVR after TAVR. There seems to be no difference in annulus rupture and 30-day mortality with either imaging modality.

Diagnostic value of mitral regurgitant jet volume in the assessment of mitral regurgitation severity by general imaging three-dimensional quantification.

Accurate quantification of mitral regurgitation (MR) severity is critical for appropriate clinical decision making regarding surgical intervention. General imaging three-dimensional quantification (GI3DQ) method allows for direct measurement of mitral regurgitant jet volume (MRJvol) with the help of three-dimensional (3D) color flow Doppler imaging. The aim of this study was to evaluate diagnostic value of MRJvol by GI3DQ for MR grading severity, using the guideline recommended integrated approach as a reference. The study included ninety-seven patients with varying degree of MR, and all MR cases were divided into central MR group (n = 44) and eccentric MR group (n = 53). The MRJvol was measured by GI3DQ. The severity of MR was graded on the basis of recommended integrated approach as mild, moderate, or severe. As assessed by receiver operating characteristic analysis, MRJvol by GI3DQ at a cutoff value of 43.4 ml yielded 76.9% of sensitivity and 86.9% of specificity to differentiate moderate from severe MR in all cases, a cutoff value of 47.5 ml yielded 98.9% of sensitivity and 94.4% of specificity to differentiate moderate from severe MR in central MR, and a cutoff value of 40.7 ml yielded 80.0% of sensitivity and 78.6% of specificity to differentiate moderate from severe MR in eccentric MR. MRJvol measured by GI3DQ could assess MR severity, especially in central MR group, which has higher sensitivity and specificity to differentiate moderate from severe MR.

The impact of different geometric assumption of mitral annulus on the assessment of mitral regurgitation volume by Doppler method.

BACKGROUND: Mitral regurgitation volume (MRvol) by quantitative pulsed Doppler (QPD) method previously recommended suffers from geometric assumption error because of circular geometric assumption of mitral annulus (MA). Therefore, the aim of this study was to evaluate the impact of different geometric assumption of MA on the assessment of MRvol by two-dimensional transthoracic echocardiographic QPD method. METHODS: This study included 88 patients with varying degrees of mitral regurgitation (MR). The MRvol was evaluated by QPD method using circular or ellipse geometric assumption of MA. MRvol derived from effective regurgitant orifice area by real time three-dimensional echocardiography (RT3DE) multiplied by MR velocity-time integral was used as reference method. RESULTS: Assumption of a circular geometry of MA, QPD-MAA4C and QPD-MAPLAX overestimated the MRvol by a mean difference of 10.4 ml (P < 0.0001) and 22.5 ml (P < 0.0001) compared with RT3DE. Assumption of an ellipse geometry of MA, there was no significant difference of MRvol (mean difference = 1.7 ml, P = 0.0844) between the QPD-MAA4C + A2C and the RT3DE. CONCLUSIONS: Assuming that the MA was circular geometry previously recommended, the MRvol by QPD-MAA4C was overestimated compared with the reference method. However, assuming that the MA was ellipse geometry, the MRvol by the QPD-MAA4C + A2C has no significant difference with the reference method.