Coronary Artery Tree Description and Lesion Evaluation (CatLet) score for functional evaluation of coronary stenosis: a comparison study with pressure wire fractional flow reserve.

Background: Pressure wire fractional flow reserve (FFR) and its derivatives, such as quantitative flow ratio (QFR), computational pressure flow-derived FFR (caFFR), coronary angiography-derived FFR (FFRangio), and computed tomography-derived FFR (FFRCT), have been validated for identifying functionally significant stenosis and guiding revascularization strategy. The limitations of using these methods include the side effects of hyperemia-induced agents, additional costs, and vulnerability to microvascular resistance. FFR is related both to the degree of a stenotic coronary artery and to its subtended myocardial territory. Coronary Artery Tree Description and Lesion Evaluation (CatLet) score (also known as Hexu) is a product of the degree of a stenosis and the weighting of the affected coronary artery (myocardial territory). Hence, we hypothesized that the CatLet score could predict hemodynamically significant coronary stenosis. Methods: We retrospectively enrolled consecutive patients with stable coronary artery disease. They attended Sichuan Science City Hospital with at least one lesion of 50-90% diameter stenosis in a coronary artery of 2 mm or larger. FFR measurement was obtained during invasive coronary angiography. The CatLet score was obtained by multiplying a fixed value of 2.0 (for non-occlusive lesions) and the weight of the affected coronary artery. The primary endpoint was the CatLet score's diagnostic accuracy in identifying hemodynamically significant coronary stenosis, with a pressure wire FFR of ≤0.80 being used as reference. Results: We analyzed the FFR and CatLet scores from 206 vessels in 175 patients with stable coronary disease and intermediate coronary lesions. The per-vessel analysis revealed an overall good correlation between the CatLet score and the FFR [r=-0.61; 95% confidence interval (95% CI): -0.69 to -0.52; P<0.01]. We also noted a significant CatLet score-FFR correlation for each of the left anterior descending artery (LAD), left circumflex (LCX), and right coronary artery (RCA). With a CatLet score ≥10 as a predictor of FFR ≤0.80, the overall diagnostic accuracy included a sensitivity of 78.80% (95% CI: 67.00-87.90%), a specificity of 85.00% (95% CI: 78.00-90.50%), a positive likelihood ratio of 5.25, a negative likelihood ratio of 0.25, and an area under the curve of 0.90 (95% CI: 0.85-0.94). Equivalent vessel-specific results were also achieved for each of the LAD, LCX, and RCA. Conclusions: The CatLet score, solely based on visual estimation of the results of coronary angiography, demonstrated good diagnostic performance with respect to myocardial ischemia. Its clinical values in guiding revascularization warrant further investigation.

Preparation of gastrodin-modified dendrimer-entrapped gold nanoparticles as a drug delivery system for cerebral ischemia-reperfusion injury.

OBJECTIVE: This study sought to evaluate the feasibility of multifunctional gastrodin (GAS)-containing nano-drug carrier system against cerebral ischemia-reperfusion injury (CIRI). METHODS: The drug-loaded nanocomposite (Au-G5.NHAc-PS/GAS) with certain encapsulation efficiency (EE) was prepared by physical adsorption method using different proportions of GAS and drug-carrying system (Au-G5.NHAc-PS). High-performance liquid chromatography was used to determine the drug loading and EE. Cultured rat astrocytes and hypothalamic neurons were assigned into four groups: PBS, Au-G5.NHAc-PS, Au-G5.NHAc-PS/GAS, and GAS. CCK-8 assay, flow cytometry, and quantitative real-time PCR were performed to examine the cell viability, apoptosis, and the expression of tumor necrosis factor-α (TNF-α), IL-1ß, and IL-6 in the astrocytes and hypothalamic neurons, respectively. Cellular uptake of GAS and Au-G5.NHAc-PS/GAS was analyzed by using Hoechst 33342 staining. The animal model with focal cerebral ischemia was generated by middle cerebral artery occlusion (MCAO) in healthy male Sprague Dawley (SD) rats, and pathological changes of brain tissue and major organs in the rats were identified by hematoxylin and eosin (HE) staining. Apoptosis in rat astrocytes and hypothalamic neurons was detected by TUNEL staining and flow cytometry. RESULTS: Au-G5.NHAc-PS had a spherical shape with a uniform size of 157.3 nm. Among the nanoparticles, Au-G5.NHAc-PS/GAS with an EE of 70.3% displayed the best release delay effect. Moreover, we observed that in vitro cytotoxicity and cellular uptake of Au-G5.NHAc-PS/GAS were higher than those of GAS, whereas the expression of TNF-α, IL-1ß, and IL-6 was significantly downregulated in Au-G5.NHAc-PS/GAS group as compared to G5.NHAc-PS group. Notably, HE staining revealed that although Au-G5.NHAc-PS/GAS had no toxic and side effects on the main organs of rats, it alleviated the damage of brain tissue in the MCAO rats. Besides, Au-G5.NHAc/GAS markedly reduced MCAO-induced apoptosis. CONCLUSION: Au-G5.NHAc-PS showed favorable surface morphology, sustained drug release ability, no measurable toxicity, and good biocompatibility, indicating that GAS exerts anti-inflammatory and antiapoptotic effects on CIRI.

Development and research progress of anti-drug resistant fungal drugs.

With the widespread use of immunosuppressive agents and the increase in patients with severe infections, the incidence of fungal infections worldwide has increased year by year. The fungal pathogens Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus cause a total of more than 1 million deaths each year. Long-term use of antifungal drugs can easily lead to fungal resistance, and the prevalence of drug-resistant fungi is a major global health challenge. In order to effectively control global fungal infections, there is an urgent need for new drugs that can exert effective antifungal activity and overcome drug resistance. We must promote the discovery of new antifungal targets and drugs, and find effective ways to control drug-resistant fungi through different ways, so as to reduce the threat of drug-resistant fungi to human life, health and safety. In the past few years, certain progress has been made in the research and development of antifungal drugs. In addition to summarizing some of the antifungal drugs currently approved by the FDA, this review also focuses on potential antifungal drugs, the repositioned drugs, and drugs that can treat drug-resistant bacteria and fungal infections, and provide new ideas for the development of antifungal drugs in the future.

Chronic vagus nerve stimulation (VNS) altered IL-6, IL-1ß, CXCL-1 and IL-13 levels in the hippocampus of rats with LiCl-pilocarpine-induced epilepsy.

An increasing number of observations have indicated that the activation of inflammatory processes is involved in the pathogenesis of epilepsy. As an effective adjunctive therapy for medically intractable seizures, vagus nerve stimulation (VNS) is thought to interact with the inflammatory process to play an antiepileptic role. In this study, we examined the levels of multiple cytokine in focal brain tissue and peripheral blood to determine whether the antiepileptic effect of chronic VNS is related to the expression of cytokines. We observed that the frequency and duration of seizures significantly decreased in epileptic rats after two weeks of chronic VNS treatment. Pathological staining showed that the number of neural cells in the hippocampus was higher in the Epi + VNS group than in the Epi group, indicating that chronic VNS had a significant neuroprotective effect on epileptic rats. After comparing the expression of 9 cytokines, we found that the levels of the proinflammatory cytokines IL-6, IL-1ß and CXCL-1 in the hippocampus were significantly increased in the Epi group, while these cytokines were significantly decreased in the Epi + VNS group. Moreover, the level of the anti-inflammatory cytokine IL-13 was found to be reduced in Epi rats, while its levels were increased after VNS treatment. However, these changes in cytokine expression were not found in the hypothalamus or peripheral blood. These results suggest that the antiepileptic mechanism of VNS may work by inhibiting the activation of inflammatory processes in the epileptogenic focus.