Diagnostic Performance of Angiography-Derived Quantitative Flow Ratio in Complex Coronary Lesions.

BACKGROUND: Quantitative flow ratio derived from computed tomography angiography (CT-QFR) and invasive coronary angiography (Murray law-based quantitative flow ratio [µQFR]) are novel approaches enabling rapid computation of fractional flow reserve without the use of pressure guidewires and vasodilators. However, the feasibility and diagnostic performance of both CT-QFR and µQFR in evaluating complex coronary lesions remain unclear. METHODS: Between September 2014 and September 2021, 240 patients with 30% to 90% coronary diameter stenosis who underwent both coronary computed tomography angiography and invasive coronary angiography with fractional flow reserve within 60 days were retrospectively enrolled. The diagnostic performance of CT-QFR and µQFR in detecting functional ischemia among all lesions, especially complex coronary lesions, was analyzed using fractional flow reserve as the reference standard. RESULTS: CT-QFR and µQFR analyses were performed on 309 and 289 vessels, respectively. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for CT-QFR in all lesions at the per-vessel level were 91% (with a 95% CI of 84%-96%), 92% (95% CI, 88%-95%), 83% (95% CI, 75%-90%), 96% (95% CI, 93%-98%), and 92% (95% CI, 88%-95%), with values for µQFR of 90% (95% CI, 81%-95%), 97% (95% CI, 93%-99%), 92% (95% CI, 84%-97%), 96% (95% CI, 92%-98%), and 94% (95% CI, 91%-97%), respectively. Among bifurcation, tandem, and moderate-to-severe calcified lesions, the diagnostic values of CT-QFR and µQFR showed great correlation and agreement with those of invasive fractional flow reserve, achieving an area under the receiver operating characteristic curve exceeding 0.9 for each complex lesion at the vessel level. Furthermore, the accuracies of CT-QFR and µQFR in the gray zone were 85% and 84%, respectively. CONCLUSIONS: Angiography-derived quantitative flow ratio (CT-QFR and µQFR) demonstrated remarkable diagnostic performance in complex coronary lesions, indicating its pivotal role in the management of patients with coronary artery disease.

Excitation characteristics of circumferential SH guided waves in steel pipes generated by EMATs with few-cycle PPM.

Circumferential Shear Horizontal (CSH) guided waves provide an effective method for detecting defects like axial cracks and corrosion in pipes. Periodic Permanent Magnet Electromagnetic Acoustic Transducers (PPM EMATs) are typically used to generate CSH guided waves. However, there is an offset problem to which little attention has been paid. The offset problem refers to the offset of the center (position of maximum energy) of the operating region caused by the variation in the peak frequency of the spatial spectra of PPM with 2 or fewer cycles. Furthermore, the excitability of guided waves is one of the factors that needs to be considered when selecting the excitation parameters of EMATs, but there are still some studies that have not sufficiently addressed this issue. In this paper, the offset problem and the excitability of CSH guided waves were investigated. Firstly, by obtaining the operating regions corresponding to PPM with different cycles, the cause and influences of the offset problem were studied. The results show that the offset in the peak frequency of the spatial spectrum of PPM is the fundamental reason causing the offset problem, and it not only leads to incorrect prediction of the excitation efficiency of guided waves but also affects the selection of the excitation parameters of EMATs. Secondly, finite element simulations and experiments were performed to assess the influence of the excitability on the excitation efficiency of the CSH0 and CSH1 modes in pipes. By analyzing the simulation and experimental results of 2-cycle PPM, as well as the simulation results for PPM with 1 to 5 cycles, the impact of the excitability on the CSH1 mode was confirmed from two perspectives. The final conclusion indicates that an accurate prediction of the amplitudes of CSH guided waves with different modes is only possible through a comprehensively consideration of the operating region of EMAT and the excitability of guided waves.

Circulating copeptin level and the clinical prognosis of patients with chronic liver disease.

BACKGROUND: The relationship between copeptin and the severity of circulatory dysfunction and systemic stress response in patients with chronic liver disease (CLD) has been established. Nevertheless, the potential of serum copeptin levels to predict the prognosis of CLD patients remains unclear. AIM: To conduct a systematic review and meta-analysis to investigate the correlation between serum copeptin and transplant-free survival (TFS) in this population. METHODS: To achieve the objective of the meta-analysis, PubMed, Embase, the Cochrane Library, and the Web of Science were searched to identify observational studies with longitudinal follow-up. The Cochrane Q test was utilized to assess between-study heterogeneity, and the I2 statistic was estimated. Random-effects models were employed to combine the outcomes, taking into account the potential influence of heterogeneity. RESULTS: Ten datasets including 3133 patients were involved. The follow-up durations were 1 to 48 mo (mean: 12.5 mo). Overall, it was shown that a high level of serum copeptin was associated with a poor TFS [risk ratio (RR): 1.82, 95% confidence interval: 1.52-2.19, P < 0.001; I2 = 0%]. In addition, sensitivity analysis by omitting one dataset at a time showed consistent results (RR: 1.73-2.00, P < 0.05). Finally, subgroup analyses according to study country, study design, patient diagnosis, cutoff of copeptin, follow-up duration, and study quality score also showed similar results (P for subgroup difference all > 0.05). CONCLUSION: Patients with CLD who have high serum copeptin concentrations may be associated with a poor clinical prognosis.

Exploring the Predictors of the Discrepancy Between Quantitative Flow Ratio and Fractional Flow Reserve Measurements.

BACKGROUND: Quantitative flow ratio is a novel technology for the functional assessment of intermediate coronary stenoses. The authors sought to explore the influence of diabetes mellitus on the application of quantitative flow ratio and predictors of discrepancies between quantitative flow ratio and fractional flow reserve. METHODS: Quantitative flow ratio was calculated in 224 patients (317 vessels) who underwent fractional flow reserve measurement by professional technicians blinded to fractional flow reserve value. Patients were divided into the diabetes mellitus group and the non-diabetes mellitus group. The diagnostic performance of quantitative flow ratio was assessed using fractional flow reserve as a reference. RESULTS: Good correlation and agreement between quantitative flow ratio and fractional flow reserve can be found in the diabetes mellitus group (r = 0.834, P <.001; mean difference: 0.007 ± 0.108). Prior myocardial infarction showed a statistically significant association with increased classification discrepancy between quantitative flow ratio and fractional flow reserve (odds ratio 3.16 (95% confidence interval: 1.29-7.75), P =.01). The area under the receiver-operating characteristic curve of quantitative flow ratio showed no significant difference in diabetes mellitus and non-diabetes mellitus groups, hemoglobin A1c ≥ 7% and hemoglobin A1c < 7% groups, diabetic duration ≥ 10 years and diabetic duration < 10 years groups (area under receiver-operating characteristic curve: 0.90 (95% confidence interval: 0.84-0.94) vs. 0.92 (95% confidence interval: 0.87-0.96), P =.54; 0.89 (95% confidence interval: 0.81-0.95) vs. 0.92 (95% confidence interval: 0.81-0.97), P =.65; 0.88 (95% confidence interval: 0.79-0.94) vs. 0.89 (95% confidence interval: 0.79-0.96), P =.83; respectively). CONCLUSIONS: Clinical application of quantitative flow ratio is not limited to diabetic patients. The relationship between prior myocardial infarction and quantitative flow ratio needs to be further developed.

cPKCγ-Modulated Autophagy Contributes to Ischemic Preconditioning-Induced Neuroprotection in Mice with Ischemic Stroke via mTOR-ULK1 Pathway.

Neuron-specific conventional protein kinase C (cPKC)γ mediates cerebral hypoxic preconditioning (HPC). In parallel, autophagy plays a prosurvival role in ischemic preconditioning (IPC) against ischemic stroke. However, the effect of cPKCγ on autophagy in IPC still remains to be addressed. In this study, adult and postnatal 1-day-old C57BL/6 J wild-type (cPKCγ+/+) and knockout (cPKCγ-/-) mice were used to establish in vivo and in vitro IPC models. The results showed that IPC pretreatment alleviated neuronal damage caused by lethal ischemia, which could be suppressed by autophagy inhibitor 3-MA or bafilomycin A1. Meanwhile, cPKCγ knockout blocked IPC-induced neuroprotection, accompanied by significant increase of LC3-I to LC3-II conversion and Beclin 1 protein level, and a significant decrease in p62 protein level. Immunofluorescent staining results showed a decrease of LC3 puncta numbers in IPC-treated cPKCγ+/+ neurons with fatal ischemia, which was reversed in cPKCγ-/- neurons. In addition, cPKCγ-modulated phosphorylation of mTOR at Ser 2448 and ULK1 at Ser 555, rather than p-Thr-172 AMPK, was detected in IPC-pretreated neurons upon lethal ischemic exposure. The present data demonstrated that cPKCγ-modulated autophagy via the mTOR-ULK1 pathway likely modulated IPC-induced neuroprotection.

Hypoxia conditioning enhances neuroprotective effects of aged human bone marrow mesenchymal stem cell-derived conditioned medium against cerebral ischemia in vitro.

Therapeutic transplantation of autologous bone marrow mesenchymal stem cells (BMSCs) holds great promise for ischemic stroke, yet the efficacy is negatively impacted by aging. Here, we examined whether hypoxia conditioning could enhance aged human BMSCs-induced neuroprotection via secretome action. Primary cultured mouse neurons were exposed to oxygen glucose deprivation (OGD) to mimic ischemic stroke in vitro, then randomized into a hypoxia conditioned aged human BMSCs-conditioned medium (BMSC-hypoCM) versus normoxia conditioned (BMSC-norCM). After 22 h of reperfusion, cell viability was significantly increased in neurons treated with BMSC-hypoCM rather than BMSC-norCM. ELISA revealed that hypoxia conditioning enhanced vascular endothelial growth factor (VEGF) release into BMSC-derived CM. Blocking the VEGF receptor negated BMSC-hypoCM-induced protection for neurons against OGD insult. Altogether, our data indicates that hypoxia conditioning improves aged human BMSCs' therapeutic efficacy for neurons with ischemic challenge, in part via promoting secretion of VEGF.

Immediate remote ischemic postconditioning reduces cerebral damage in ischemic stroke mice by enhancing leptomeningeal collateral circulation.

Remote ischemic postconditioning (RIPC) is a promising neuroprotective strategy for ischemic stroke. Here, we employed a focal ischemic stroke mouse model to test the hypothesis that poststroke collateral circulation as a potent mechanism of action underlying the therapeutic effects of immediate RIPC. During reperfusion of cerebral ischemia, the mice were randomly assigned to receive RIPC, granulocyte colony-stimulating factor (G-CSF) as a positive control, or no treatment. At 24 hr, we found RIPC and G-CSF increased monocytes/macrophages in the dorsal brain surface and in the spleen, coupled with enhanced leptomeningeal collateral flow compared with nontreatment group. Blood monocytes depletion by 5-fluorouracil (5-FU) significantly limited the neuroprotection of RIPC or G-CSF treatment. The protein expression of proangiogenic factors such as Ang-2 was increased by ischemia, but treatment with either RIPC or G-CSF showed no further upregulation. Thus, immediate RIPC confers neuroprotection, in part, by enhancing leptomeningeal collateral circulation in a mouse model of ischemic stroke.

Prenatal stress induced gender-specific alterations of N-methyl-d-aspartate receptor subunit expression and response to Aß in offspring hippocampal cells.

Prenatal stress (PS) is one of adverse life events during pregnancy, which may increase vulnerability to cognitive impairment in adult offspring. Aß synaptotoxicity is one important pathological factor for cognitive impairment, and PS-induced cognitive disorder is closely associated with N-Methyl-d-Aspartate receptor (NMDAR), which acts as a key mediator of Aß synaptotoxicity. In the present study, we tried to explore whether PS affects offspring's Aß levels and NMDAR subunit expression in a gender-specific manner in hippocampal CA and DG subregions, and whether PS affects synaptic proteins and NMDAR subunit expression in cultured offspring hippocampal cells exposed to Aß. Pregnant SD rats with restraint stress from gestation day 8-20 were used as PS model. Morris water maze, ELISA, immunofluorescence and western blot were tested on postnatal day 90 in male and female PS offspring. Our results showed that female offspring is more vulnerable to PS-induced cognitive impairment. Surprisingly, PS enhanced Aß1-40 levels in the hippocampal DG subregion of male offspring. Furthermore, WB results implied that the decreased GluN2A in CA of female may contribute to the PS-induced cognitive impairment, while in DG, the increased GluN2A and decreased GluN2B contributed to protective effects against Aß. Interestingly, we found PS could alleviate Aß synaptotoxicity in male offspring's hippocampal cells. Overall, our results provided a fundamental understanding of PS-induced gender-specific alterations of NMDAR subunit expression and the susceptibility to Aß, and paved the road for the development of timely preventive interventions on cognitive disorders of PS offspring.

Identification of IL-17A-derived neural cell type and dynamic changes of IL-17A in serum/CSF of mice with ischemic stroke.

BACKGROUND: Interleukin (IL)-17A was reported to be involved in the development of post-ischemic stroke inflammatory response and functional recovery. However, the IL-17A dynamic changes in serum/cerebrospinal fluid (CSF) and its role in neuronal injury following ischemic stroke are unclear. METHODS: In vivo ischemic stroke was induced by 1 h of middle cerebral artery occlusion (MCAO) and 6 h-7 d reperfusion (R) in mice, while in vitro stroke was induced by 1 h oxygen-glucose deprivation (OGD)/24 h reoxygenation (R) in cultured cortical neurons. Enzyme-linked immunosorbent assay (ELISA) and double-labeled immunofluorescence of IL-17A with neuron (NeuN), astrocyte (GFAP) and microglia (Iba-1)-specific markers were used to determine the IL-17A levels in serum/CSF and neural cell type. RESULTS: The ELISA results showed that IL-17A significantly increased both in peri-infarct region (p < 0.001) and CSF (p < 0.05) following 1 h MCAO/R 12 h. The levels of IL-17A in serum increased at R 1 d (p < 0.05) and peaked at R 3 d (p < 0.001) after 1 h MCAO. Immunofluorescent staining demonstrated that IL-17A co-localized with GFAP in peri-infarct regions. In addition, recombinant rIL-17A could aggravate ischemic injuries at dose-dependent manner in 1 h OGD/R 24 h-treated neurons companying with the increase of IL-17A receptor il-17RA mRNA (p < 0.001) and IL-17R protein levels. CONCLUSION: We firstly reported astrocytic IL-17A peaks in CSF within 12 h and in serum at 3 d reperfusion after ischemic stroke. IL-17A may exaggerate neuronal injuries through its receptor IL-17R at early stage of ischemic stroke.