Targeting ferroptosis in the neurovascular unit: A promising approach for treating diabetic cognitive impairment.

The cognitive decline associated with chronic metabolic disease diabetes has garnered extensive scrutiny, yet its pathogenesis remains incompletely understood, and the advancement of targeted therapeutics has posed a persistent challenge. Ferroptosis, a novel form of cell death characterized by intracellular lipid peroxidation and iron overload, has recently emerged as a significant factor. Numerous contemporary studies have corroborated that ferroptosis within the neurovascular unit is intimately associated with the onset of diabetes-induced cognitive impairment. Numerous contemporary studies have corroborated that ferroptosis within the neurovascular unit is intimately associated with the onset of diabetic cognitive impairment (DCI). This article initially conducts a profound analysis of the mechanism of ferroptosis, followed by a detailed elucidation of the specific manifestations of neurovascular unit ferroptosis in the context of diabetic cognitive function impairment. Furthermore, an exhaustive review of pertinent literature from April 2020 to March 2024 has been undertaken, resulting in the selection of 31 documents of significant reference value. These documents encompass studies on 11 distinct drugs, all of which are centered around investigating methods to inhibit the ferroptosis pathway as a potential treatment for DCI. Simultaneously, we conducted a review of 12 supplementary literary sources that presented 10 pharmacological agents with anti-ferroptosis properties in other neurodegenerative disorders. This article critically examines the potential influence of neurovascular unit ferroptosis on the progression of cognitive impairment in diabetes, from the three aforementioned perspectives, and organizes the existing and potential therapeutic drugs. It is our aspiration that this article will serve as a theoretical foundation for scholars in related disciplines when conceptualizing, investigating, and developing novel clinical drugs for DCI.

Ferrostatin-1 alleviates skin inflammation and inhibits ferroptosis of neutrophils and CD8+ T cells in allergic contact dermatitis.

BACKGROUND: Ferroptosis is considered as an immunogenic type of regulated cell death and associated with the pathogenesis of inflammatory skin diseases. However, the involvement and function of ferroptosis in allergic contact dermatitis (ACD) remains unknown. OBJECTIVE: To explore the role of ferroptosis in ACD. To reveal which type of cells develops ferroptosis in ACD. METHODS: We detected the key markers of ferroptosis in 1-Chloro-2,4-dinitrochlorobenzene (DNCB)-induced ACD mice model. We applicated ferrostatin-1 (Fer-1) to restrain ferroptosis in ACD mice and then compared the severity of dermatitis and the level of inflammation and ferroptosis in dermis and epidermis, respectively. Keratinocyte-specific Gpx4 conditional knockout (cKO) mice were used to investigate the function of keratinocyte ferroptosis in the development of ACD. Single-cell RNA sequencing was conducted to analyze the affection of Fer-1 on different type of cells in ACD. RESULTS: Ferroptosis was involved in DNCB-induced ACD mice. Ferroptosis activation was more remarkable in dermis rather than in epidermis. Gpx4 cKO mice showed similar severity of skin dermatitis as control mice. Fer-1 alleviated skin inflammation in mice and reduced ferroptosis in neutrophils and CD8+ T cells both of which contribute to development of ACD. CONCLUSION: Ferroptosis was activated in immune cells, especially neutrophils and CD8+ T cells in DNCB-induced ACD mice. Fer-1 treatment inhibited ferroptosis of neutrophils and CD8+ T cells and relieved skin damage in ACD mice.

A qualitative analysis of Chinese higher education students' intentions and influencing factors in using ChatGPT: a grounded theory approach.

The emergence of ChatGPT has significantly impacted the field of education. While much of the existing research has predominantly examined the theoretical implications of ChatGPT, there is a notable absence of empirical studies substantiating these claims. As pivotal stakeholders in education and primary users of ChatGPT, exploring the willingness and influencing factors of higher education students to use ChatGPT can offer valuable insights into the real-world needs of student users. This, in turn, can serve as a foundation for empowering education with intelligent technologies in the future. This study focuses specifically on the demographic of students in Chinese higher education who have utilized ChatGPT. Using semi-structured interviews and grounded theory methodology, we aim to comprehensively understand the extent to which students embrace new technologies. Our objective is to elucidate the behavioral inclinations and influencing factors of student users. The findings of this study will contribute practical insights for refining policy frameworks, expanding the dissemination of quality resources, optimizing and upgrading products for an enhanced user experience, and fostering higher-order thinking skills to adeptly navigate evolving technological landscapes. In conclusion, this research endeavors to bridge the gap between theoretical discussions and practical applications.

Modular Design of Functional Glucose Monomer and Block Co-Polymer toward Stable Zn Anodes.

Aqueous Zn batteries employing mildly acidic electrolytes have emerged as promising contenders for safe and cost-effective energy storage solutions. Nevertheless, the intrinsic reversibility of the Zn anode becomes a focal concern due to the involvement of acidic electrolyte, which triggers Zn corrosion and facilitates the deposition of insulating byproducts. Moreover, the unregulated growth of Zn over cycling amplifies the risk of internal short-circuiting, primarily induced by the formation of Zn dendrites. In this study, a class of glucose-derived monomers and a block copolymer are synthesized through a building-block assembly strategy, ultimately leading to uncover the optimal polymer structure that suppresses the Zn corrosion while allowing efficient ion conduction with a substantial contribution from cation transport. Leveraging these advancements, remarkable enhancements are achieved in the realm of Zn reversibility, exemplified by a spectrum of performance metrics, including robust cycling stability without voltage overshoot and short-circuiting during 3000 h of cycling, stable operation at a high depth of charge/discharge of 75% and a high current density, >95% Coulombic efficiency over 2000 cycles, successful translation of the anode improvement to full cell performance. These polymer designs offer a transformative path based on the modular synthesis of polymeric coatings toward highly reversible Zn anode.

Crosstalk between intestinal flora and human iron metabolism: the role in metabolic syndrome-related comorbidities and its potential clinical application.

The interaction of iron and intestinal flora, both of which play crucial roles in many physiologic processes, is involved in the development of Metabolic syndrome (MetS). MetS is a pathologic condition represented by insulin resistance, obesity, dyslipidemia, and hypertension. MetS-related comorbidities including type 2 diabetes mellitus (T2DM), obesity, metabolism-related fatty liver (MAFLD), hypertension polycystic ovary syndrome (PCOS), and so forth. In this review, we examine the interplay between intestinal flora and human iron metabolism and its underlying mechanism in the pathogenesis of MetS-related comorbidities. The composition and metabolites of intestinal flora regulate the level of human iron by modulating intestinal iron absorption, the factors associated with iron metabolism. On the other hand, the iron level also affects the abundance, composition, and metabolism of intestinal flora. The crosstalk between these factors is of significant importance in human metabolism and exerts varying degrees of influence on the manifestation and progression of MetS-related comorbidities. The findings derived from these studies can enhance our comprehension of the interplay between intestinal flora and iron metabolism, and open up novel potential therapeutic approaches toward MetS-related comorbidities.

Bio-Inspired Dynamically Morphing Microelectronics toward High-Density Energy Applications and Intelligent Biomedical Implants.

Choreographing the adaptive shapes of patterned surfaces to exhibit designable mechanical interactions with their environment remains an intricate challenge. Here, a novel category of strain-engineered dynamic-shape materials, empowering diverse multi-dimensional shape modulations that are combined to form fine-grained adaptive microarchitectures is introduced. Using micro-origami tessellation technology, heterogeneous materials are provided with strategic creases featuring stimuli-responsive micro-hinges that morph precisely upon chemical and electrical cues. Freestanding multifaceted foldable packages, auxetic mesosurfaces, and morphable cages are three of the forms demonstrated herein of these complex 4-dimensional (4D) metamaterials. These systems are integrated in dual proof-of-concept bioelectronic demonstrations: a soft foldable supercapacitor enhancing its power density (≈108 mW cm-2), and a bio-adaptive device with a dynamic shape that may enable novel smart-implant technologies. This work demonstrates that intelligent material systems are now ready to support ultra-flexible 4D microelectronics, which can impart autonomy to devices culminating in the tangible realization of microelectronic morphogenesis.

Risk Factors and Nomogram Model of Postoperative Delirium in Children with Congenital Heart Disease: A Single-Center Prospective Study.

Delirium is a common postoperative complication in children with congenital heart disease, which affects their postoperative recovery. The purpose of this study is to explore the risk factors of delirium and construct a nomogram model to provide novel references for the prevention and management of postoperative delirium in children with congenital heart disease. 470 children after congenital heart surgery treated in the cardiac intensive care unit (CICU) of Shanghai Children's Medical Center were divided into a model and a validation cohort according to the principle of 7:3 distribution temporally. Then, the delirium-related influencing factors of 330 children in the training cohort were analyzed, and the nomogram model was established by a combination of Lasso regression and logistic regression. The data of 140 children in the validation cohort were used to verify the effectiveness of the model. Multivariable logistic regression analysis showed that age, disease severity, non-invasive ventilation after extubation, delayed chest closure, phenobarbital dosage, promethazine dosage, mannitol usage, and elevated temperature were independent risk factors for postoperative delirium. The area under the receiver operating characteristic curve (AUC) of the nomogram model was 0.864 and the Brier value was 0.121. Regarding the validation of the model's effect, our results showed that 51 cases were predicted by the model and 34 cases actually occurred, including 4 cases of false negative and 21 cases of false positive. The positive predictive value of the model was 58.8%, and its negative predictive value was 95.5%. The nomogram model established in this study showed acceptable performance in predicting postoperative delirium in children with congenital heart disease.

Research Advance of Chinese Medicine in Treating Atherosclerosis: Focus on Lipoprotein-Associated Phospholipase A2.

As a serious cardiovascular disease, atherosclerosis (AS) causes chronic inflammation and oxidative stress in the body and poses a threat to human health. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of the phospholipase A2 (PLA2) family, and its elevated levels have been shown to contribute to AS. Lp-PLA2 is closely related to a variety of lipoproteins, and its role in promoting inflammatory responses and oxidative stress in AS is mainly achieved by hydrolyzing oxidized phosphatidylcholine (oxPC) to produce lysophosphatidylcholine (lysoPC). Moreover, macrophage apoptosis within plaque is promoted by localized Lp-PLA2 which also promotes plaque instability. This paper reviews those researches of Chinese medicine in treating AS via reducing Lp-PLA2 levels to guide future experimental studies and clinical applications related to AS.

Zn Microbatteries Explore Ways for Integrations in Intelligent Systems.

As intelligent microsystems develop, many revolutionary applications, such as the swallowing surgeon proposed by Richard Feynman, are about to evolve. Nonetheless, integrable energy storage satisfying the demand for autonomous operations has emerged as a major obstacle to the deployment of intelligent microsystems. A reason for the lagging development of integrable batteries is the challenge of miniaturization through microfabrication procedures. Lithium batteries, generated by the most successful battery chemistry, are not stable in the air, thus creating major manufacturing challenges. Other cations (Na+ , Mg2+ , Al3+ , K+ ) are still in the early stages of development. In contrast, the superior stability of zinc batteries in the air brings high compatibility to microfabrication protocols and has already demonstrated excellent practicability in full-sized devices. To obtain energy-dense and high-power zinc microbatteries within square-millimeter or smaller footprints, sandwich, pillar, and Swiss-roll configurations are developed. Thin interdigital and fiber microbatteries find their applications being integrated into wearable devices and electronic skin. It is foreseeable that zinc microbatteries will find their way into highly integrated microsystems unlocking their full potential for autonomous operation. This review summarizes the material development, configuration innovation, and application-oriented integration of zinc microbatteries.

Effects of Aspergillus niger on cyanogenic glycosides removal and fermentation qualities of ratooning sorghum.

Introduction: Cyanogenic glycosides (CNglcs) are bioactive plant products involving in plant defense against herbivores by virtue of their abilities to release toxic hydrogen cyanide (HCN). Aspergillus niger has been shown to be effective in producing ß-glucosidase, which could degrade CNglcs. However, whether A. niger could remove CNglcs under ensiling conditions is still unknown. Methods: In this study, we first investigated the HCN contents in ratooning sorghums for two years, then the sorghums were ensiled with or without the addition of A. niger. Results: Two years' investigation indicated that the contents of HCN in fresh ratooning sorghum were larger than 801 mg/kg FW (fresh weight), which could not be reduced by silage fermentation under safety threshold (200 mg/kg FW). A. niger could produce ß-glucosidase over a range of pH and temperature, which degraded the CNglcs and removed the hydrogen cyanide (HCN) at early days of ratooning sorghum fermentation. The addition of A. niger (2.56 × 107 CFU/ml) altered the microbial community, increased bacterial diversity, improved the nutritive qualities, and reduced the HCN contents in ensiled ratooning sorghum lower than 100 mg/kg FW after 60 days of fermentation. Overall, the addition of 150 ml A. niger + 50 ml sterile water per 3 kg silage could efficiently remove CNglcs from ratooning sorghum silage. Conclusion: In conclusion, A. niger could produce ß-glucosidase which degraded the CNglcs during the early days of fermentation, benefiting the ensiling process and improving the utilization of ratooning sorghum.

Study on Virulence Genes, Drug Resistance and Molecular Epidemiology of Klebsiella pneumoniae with High Virulence in Inner Mongolia, China.

Objective: The purpose of this study was to analyse the clinical, microbiological and molecular epidemiological characteristics of patients with pyogenic liver abscess (PLA) caused by Klebsiella pneumoniae (KPN) in Inner Mongolia, China. Methods: The KPN isolates from 78 KPN-PLA cases admitted to a tertiary teaching hospital in Baotou, Inner Mongolia, from 2016 to 2019 were studied systematically and described comprehensively. The virulence factors, drug resistance and sequence types of KPN in different samples were identified by a wire-drawing test, polymerase chain reaction, a drug susceptibility test and multi-site sequence typing. Results: There were more male than female KPN-PLA patients (P<0.05). The mortality rate was 2.5%, and KPN-PLA was significantly associated with diabetes mellitus (P<0.05). Most of the KPN isolates in the puncture fluid of patients with KPN-PLA were hypervirulent KPN (HvKP). The positive rate of the KPN-PLA specimens was higher than that of the blood and urine specimens. The KPN isolates of the urine specimens had higher drug resistance than the other two (P<0.05). The hypermucoviscous KPN, aerobic actin (aero) (+), K1 and K2 serotypes accounted for 80.8%, 89.7%, 56.4% and 26.9%, respectively. In addition to ironB (3.8%), the detection rates of virulence factors rmpA, irp2, entB, iucD, aero, wcaG, iutA, kfu, ybtA, iron, fimH and mrkD were higher (69.2%-100.0%). The positive rate of KPN isolates of the KPN-PLA puncture fluid was higher than that of the blood and urine samples (P<0.05). In addition, ST23 was found to be the dominant ST (32.1%) of KPN-PLA in the Baotou region. Conclusion: In the KPN-PLA specimens, the KPN isolates were more virulent than those in the blood and urine specimens, and a carbapenem-resistant HvKP strain emerged. This research will help improve the understanding of HvKP and provide useful suggestions for KPN-PLA treatments.

Diversified chemical profiles of cuticular wax on alpine meadow plants of the Qinghai-Tibet Plateau.

MAIN CONCLUSION: The alpine meadow plants showed great intra- and inter-genera variations of chemical profiles of cuticular waxes. Developing an understanding of wax structure-function relationships that will help us tackle global climate change requires a detailed understanding of plant wax chemistry. The goal in this study was to provide a catalog of wax structures, abundances, and compositions on alpine meadow plants. Here, leaf waxes from 33 plant species belonging to 11 families were sampled from alpine meadows of the east side of the Qinghai-Tibet Plateau. Across these species, total wax coverage varied from 2.30 µg cm-2 to 40.70 µg cm-2, showing variation both within as well as between genera and suggesting that wax variation is subject to both environmental and genetic effects. Across all wax samples, more than 140 wax compounds belonging to 13 wax compound classes were identified, including both ubiquitous wax compounds and lineage-specific compounds. Among the ubiquitous compounds (primary alcohols, alkyl esters, aldehydes, alkanes, and fatty acids), chain length profiles across a wide range of species point to key differences in the chain length specificity of alcohol and alkane formation machinery. The lineage-specific wax compound classes (diols, secondary alcohols, lactones, iso-alkanes, alkyl resorcinols, phenylethyl esters, cinnamate esters, alkyl benzoates, and triterpenoids) nearly all consisted of isomers with varying chain lengths or functional group positions, making the diversity of specialized wax compounds immense. The comparison of species relationships between chemical data and genetic data highlighted the importance of inferring phylogenetic relationships from data sets that contain a large number of variables that do not respond to environmental stimuli.

Does pre-incubation in selective-enrichment media improve the detection of diarrheagenic Escherichia coli using the RIDA®GENE PCR?

We aimed to investigate whether a selective pre-PCR enrichment step improves test performance of RIDA®GENE EHEC/EPEC to detect diarrheagenic Escherichia coli from stool samples. Each of the 250 stool samples was analyzed for the presence of stx1/2 and eae both with and without pre-PCR enrichment in selective broth. In comparison to a reference method, sensitivities for stx1/2 and eae with and without pre-PCR enrichment were 84% (95%CI 70-93) and 89% (stx1/2, 95%CI 76-96), and 71% (95%CI 58-81) and 72% (eae, 95%CI 60-82), respectively. Specificity exceeded 97% for both methods and target genes. In summary, pre-PCR broth enrichment did not improve test performance.

Expression and Localization of Fas-Associated Factor 1 in Testicular Tissues of Different Ages and Ovaries at Different Reproductive Cycle Phases of Bos grunniens.

Fas-associated factor 1 (FAF1), a member of the Fas family, is involved in biological processes such as apoptosis, inflammation, cell proliferation and proteostasis. This study aimed to explore the biological role of FAF1 in testicular tissue at different ages (juveniles (1 and 2 years old), adults (3, 4, 6, and 7 years old) and old-aged animals (11 years old)) and ovaries during different reproductive cycle phases (follicular, luteal, and pregnancy phases). FAF1 mRNA, relative protein expression and protein expression localization were determined in testes and ovaries using real-time quantification, WB and immunohistochemistry (IHC), respectively. Real-time quantification of testis tissues showed that the relative expression of FAF1 mRNA in testis tissues at 3, 4 and 7 years of age was significantly higher than of those in other ages, and in ovarian tissues was significantly higher in luteal phase ovaries than those in follicular and pregnancy phase ovaries; follicular phase ovaries were the lowest. WB of testis tissues showed that the relative protein expression of FAF1 protein was significantly higher at 11 and 7 years of age; in ovarian tissue, the relative protein expression of FAF1 protein was significantly higher in follicular phase ovaries than in luteal and pregnancy phase ovaries, and lowest in luteal phase ovaries. The relative protein expression of FAF1 at 3, 4 and 7 years of age was the lowest. IHC showed that FAF1 was mainly expressed in spermatozoa, spermatocytes, spermatogonia and supporting cells; in ovarian tissue, FAF1 was expressed in ovarian germ epithelial cells, granulosa cells, cumulus cells and luteal cells. The IHC results showed that FAF1 mRNA and protein were significantly differentially expressed in testes of different ages and ovarian tissues of different reproductive cycle phases, revealing the significance of FAF1 in the regulation of male and female B. grunniens reproductive physiology. Furthermore, our results provide a basis for the further exploration of FAF1 in the reproductive physiology of B. grunniens.

Reduction of miR-133a-3p contributes to apoptosis and gasdermin E-mediated pyroptosis of keratinocytes in skin exposed to ultraviolet B radiation.

Engagement of regulated cell death in keratinocytes plays a crucial role in the pathogenesis and development of skin disorders associated with UV radiation. However, it remains unclear how microRNAs (miRNAs) participate in the regulation of UV-caused keratinocyte death. In this study, we found that miR-133a-3p was decreased in the epidermis of UVB-challenged mice and UVB-irradiated keratinocyte cell line HaCaT cells. The intradermal injection of agomir miR-133a-3p ameliorated skin damage of UVB-challenged mice, especially epidermal necrosis. Meanwhile, the injection inhibited apoptosis indicator PARP cleavage and pyroptosis indicator GSDME cleavage in the epidermis. In UVB-challenged HaCaT cells, transfection of miR-133a-3p mimic or inhibitor alleviated or aggravated UVB-induced apoptosis and GSDME-mediated pyroptosis respectively. miR-133a-3p was also involved in the effects of metformin treatment on alleviating skin damage in UVB-challenged mice and on inhibiting apoptosis and GSDME-mediated pyroptosis in UVB-irradiated HaCaT cells. We confirmed that CYLD is a target gene of miR-133a-3p and participates in the protective effects of miR-133a-3p on inhibiting UVB-caused apoptosis and GSDME-mediated pyroptosis in keratinocytes. This study indicates a pivotal role for miR-133a-3p of keratinocytes in UVB-caused skin damage. Alleviating skin photodamage by restoring the decrease of miR-133a-3p can be considered a potential therapeutic approach.

In situ observations of tungsten speciation and partitioning behavior during fluid exsolution from granitic melt.

Most economically important tungsten (W) deposits are of magmatic-hydrothermal origin. The species and partitioning of W during fluid exsolution, considered to be the controlling factors for the formation of ore deposits, are thus of great significance to investigate. However, this issue has not been well addressed mainly due to the significant difference in reported partition coefficients (e.g., from strongly incompatible to strongly compatible) between fluid and melt (DWfluid/melt). Here, we used an in situ Raman spectroscopic approach to describe the W speciation, and to quantitatively determine the Dfluid/melt of individual and total W species in granite melts and coexisting Na2WO4 solutions at elevated temperatures (T; 700-800 °C) and pressures (P; 0.35-1.08 GPa). Results show that WO42- and HWO4- are predominant W species, and the fractions of these two species are similar in melt and coexisting fluid. The partitioning behaviors of WO42- and HWO4- are comparable, exhibiting strong enrichment in the fluid. The total DWfluid/melt ranges from 8.6 to 37.1. Specifically, DWfluid/melt decreases with rising T-P, indicating that shallow exsolution favors enrichment of W in evolved fluids. Furthermore, Rayleigh fractionation modeling based on the obtained DWfluid/melt data was used to describe the fluid exsolution processes. Our results strongly support that fluid exsolution can serve as an important mechanism to generate W-rich ore-forming fluids. This study also indicates that in situ approach can be used to further investigate the geochemical behavior of ore-forming elements during the magmatic-hydrothermal transition, especially for rare metals associated with granite and pegmatite.

Academic expectations among international students from North-Western China: A case of technology use during and post COVID-19.

This study examines the influence of the COVID-19 crisis on academic expectations among international students from north-western China. According to past studies, academic expectations are multifaceted, making it critical to test the methods employed to assess this fundamental trait. The outbreak of COVID-19 has resulted in various significant changes in education, which have shifted from traditional to online or mixed formats. As a result, examining international students' academic expectations along with their interactions with adopted technologies is a topic that addresses the current situation and issues. A mixed approach, comprising two different instruments (questionnaire and interview), was followed to achieve this primary objective. While a survey with a questionnaire was undertaken with 551 international students, divided into two groups, ten students were interviewed during and after the lockdowns. The findings revealed that COVID-19 had a significant impact on the academic expectations of students as well as many elements such as training for employment, personal and social development, international student mobility, motivation, social pressure, and social interaction with the help of supporting technologies. In terms of gender, men outperformed women in motivation, social interaction, training for employment, and personal and social development factors. Similarly, as per the grade variable (undergraduate, postgraduate, doctoral), the same higher trend was seen in postgraduates. Based on these findings, a set of recommendations was put forward. In the future, technology will be helpful in China's educational sector, such as online group collaboration, open education, managing student retention, and supervising teachers' recruitment.

Construction and validation of an early prediction model of delirium in children after congenital heart surgery.

Background: Delirium often occurs in children with congenital heart disease in the early postoperative period, which is not conducive to the rehabilitation and prognosis. There is little evidence to prove the effectiveness and safety of drug treatment of delirium in children, and the prevention has become an important topic. The purpose of this study is to analyze the early risk factors of delirium in children after congenital heart surgery, establish a nomogram prediction model, and explore the application efficiency of the model, so as to provide reference for early prevention of delirium. Methods: A total of 362 children treated in the cardiac intensive care unit (CICU) of Shanghai Children's Medical Center after congenital heart surgery from February 15 to April 15, 2021 were enrolled for the construction of the model. Bedside nurses who received unified training used the Cornell Assessment of Pediatric Delirium (CAPD) to evaluate delirium and recorded sixteen preoperative- and intraoperative-related influencing factors. A nomogram prediction model was created using multivariate logistic regression. The prediction effect of the model was evaluated by C-index and Brier value, and 96 children from April 16 to May 15, 2021 were included for effect verification. The model's effectiveness was validated by comparing the occurrence of delirium in children predicted by the model with the actual occurrence. Results: Multivariate logistic regression analysis showed that male gender [odds ratio (OR) =1.786, 95% confidence interval (CI): 1.018-3.134, P=0.043], age <6.5 months (OR =0.224, 95% CI: 0.126-0.399, P=0.000), disease severity ≥4 points (OR =6.955, 95% CI: 3.564-13.576, P=0.003), and operation time ≥148 min (OR =2.401, 95%CI: 1.336-4.315, P=0.000) were independent risk factors for delirium in children after cardiac surgery. The C-index of the nomogram prediction model was 0.808, sensitivity was 76.1%, specificity was 70%, and the Brier value was 0.142. The validation of the model showed that the model predicted 20 cases and the actual occurrence was 20 cases, of which 8 cases were false negative and 8 cases were false positive, and the sensitivity, specificity, and accuracy of the model were 60%, 89.5%, and 83.3%, respectively. Conclusions: The prediction model constructed in this study could provide early prediction of the occurrence of delirium in children after congenital heart surgery to a certain extent.

Effect of PCSK9 Inhibitor on Blood Lipid Levels in Patients with High and Very-High CVD Risk: A Systematic Review and Meta-Analysis.

Objectives: We aimed to investigate the effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor on blood lipid levels in patients with high and very-high cardiovascular risk. Design: 14 trials (n = 52,586 patients) comparing treatment with or without PCSK9 inhibitors were retrieved from PubMed and Embase updated to 1st Jun 2021. The data quality of included studies was assessed by two independent researchers using the Cochrane systematic review method. All-cause mortality, cardiovascular mortality, and changes in serum low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), apolipoprotein B (ApoB), lipoprotein (a) (LP (a)), non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein A1 (ApoA1) from baseline were analyzed using Rev Man 5.1.0 software. Results: Compared with treatments without PCSK9 inhibitor, addition of PCSK9 inhibitors (evolocumab and alirocumab) had obvious decreasing effects on the levels of LDL-C [MD = -46.86, 95% CI (-54.99 to -38.72), P < 0.00001], TC [MD = -31.92, 95% CI (-39.47 to -24.38), P < 0.00001], TG [MD = -8.13, 95% CI (-10.48 to -5.79), P < 0.00001], LP(a) [MD = -26.69, 95% CI (-27.93 to -25.44), P < 0.00001], non-HDL-C [MD = -42.86, 95% CI (-45.81 to -39.92), P < 0.00001], and ApoB [MD = -38.44, 95% CI (-42.23 to -34.65), P < 0.00001] in high CVD risk patients. Conversely, changes of HDL-C [MD = 6.27, CI (5.17 to 7.36), P < 0.00001] and ApoA1 [MD = 4.33, 95% CI (3.53 to 5.13), P < 0.00001] from baseline were significantly more in high cardiovascular disease risk patients who received PCSK9 inhibitors treatment. Conclusion: Addition of PCSK9 inhibitors to standard therapy resulted in definite improvement in blood lipid levels compared with therapies that did not include them.

Focus on the role of mitochondria in NLRP3 inflammasome activation: A prospective target for the treatment of ischemic stroke (Review).

Post­ischemic neuroinflammation induced by the innate local immune response is a major pathophysiological feature of cerebral ischemic stroke, which remains the leading cause of mortality and disability worldwide. NLR family pyrin domain containing (NLRP)3 inflammasome crucially mediates post­ischemic inflammatory responses via its priming, activation and interleukin­1ß release during hypoxic­ischemic brain damage. Mitochondrial dysfunctions are among the main hallmarks of several brain diseases, including ischemic stroke. In the present review, focus was addressed on the role of mitochondria in cerebral ischemic stroke while keeping NLRP3 inflammasome as a link. Under ischemia and hypoxia, mitochondria are capable of controlling NLRP3 inflammasome­mediated neuroinflammation through mitochondrial released contents, mitochondrial localization and mitochondrial related proteins. Thus, inflammasome and mitochondria may be attractive targets to treat ischemic stroke as well as the several drugs that target the process of mitochondrial function to treat cerebral ischemic stroke. At present, certain drugs have already been studied in clinical trials.