Time to benefit of colchicine in patients with cardiovascular disease: A pooled analysis of randomized controlled trials.

Background: Low-dose colchicine has been shown to lower major adverse cardiovascular events (MACE) among those with cardiovascular disease (CVD). It remains unclear how long a CVD patient needs to live to potentially benefit from colchicine. Our study aimed to determine the time to benefit (TTB) of colchicine in individuals with CVD. Methods: Literature searches were performed in PubMed for the cardiovascular outcome trial of colchicine in patients with CVD until October 12, 2023. The primary outcome measured was MACE. Reconstructed individual participant data (IPD) and the stratified Cox proportional hazards model were used to calculate the hazard ratio (HR) and 95 % confidence interval (CI) to estimate the efficacy of colchicine, and Weibull survival curves were fitted to estimate TTB for specific absolute risk reduction (ARR) thresholds (0.002, 0.005, and 0.01). Results: Four trials randomizing 11,594 adults aged between 59.8 and 66.5 years were included (follow-up duration: 12-28.6 months). Compared with placebo, colchicine reduced the risk of MACE (HR 0.68, 95 % CI: 0.60 to 0.78) but had no impact on cardiovascular and all-cause mortality. A TTB of 11.0 months (95 % CI: 0.59 to 21.3) was estimated to be needed to prevent 1 MACE in 100-colchicine-treated patients. The TTB for acute coronary syndrome was similar compared to stable coronary artery disease (10.7 vs. 11.2 months for ARR = 0.010). Conclusions: By using reconstructed IPD, this pooled analysis demonstrated that colchicine was associated with reduced nonfatal MACE, and the TTB was approximately 11.0 months to prevent 1 MACE per 100 patients.

Ganoderma lucidum spores-derived particulate ß-glucan treatment improves antitumor response by regulating myeloid-derived suppressor cells in triple-negative breast cancer.

Granular ß-1,3-glucan extracted from the wall of Ganoderma lucidum spores, named GPG, is a bioregulator. In this study, we investigated the structural, thermal, and other physical properties of GPG. We determined whether GPG ameliorated immunosuppression caused by Gemcitabine (GEM) chemotherapy. Triple-negative breast cancer mice with GPG combined with GEM treatment had reduced tumor burdens. In addition, GEM treatment alone altered the tumor microenvironment(TME), including a reduction in antitumor T cells and a rise in myeloid-derived suppressor cells (MDSC) and regulatory T cells (Tregs). However, combined GPG treatment reversed the tumor immunosuppressive microenvironment induced by GEM. GPG inhibited bone marrow (BM)-derived MDSC differentiation and reversed MDSC expansion induced by conditioned medium (CM) in GEM-treated E0771 cells through a Dectin-1 pathway. In addition, GPG downgraded PD-L1 and IDO1 expression on MDSC while boosting MHC-II, CD86, TNF-α, and IL-6 expression. In conclusion, this study demonstrated that GPG could alleviate the adverse effects induced by GEM chemotherapy by regulating TME.

A network pharmacology-based method to explore the therapeutic effect of honokiol on diabetes with comorbid depression in mice.

The effective treatment of diabetes with comorbid depression is a big challenge so far. Honokiol, a bioactive compound from the dietary supplement Magnolia officinalis extract, possesses multiple health benefits. The present study aims to propose a network pharmacology-based method to elucidate potential targets of honokiol in treating diabetes with comorbid depression and related mechanisms. The antidepressant-like efficacy of honokiol was evaluated in high-fat diet (HFD) induced diabetic mice using animal behavior testing, immuno-staining and western blotting assay. Through network pharmacology analysis, retinoid X receptor alpha (RXRα) and vitamin D receptor (VDR) were identified as potential targets related to diabetes and depression. The stable binding conformation between honokiol and RXR/VDR was determined by molecular docking simulation. Moreover, hononkiol effectively alleviated depression-like behaviors in HFD diabetic mice, presented anti-diabetic and anti-neuroinflammatory functions, and protected the hippocampal neuroplasticity. Importantly, honokiol could activate RXR/VDR heterodimer in vivo. The beneficial effects of honokiol on HFD mice were significantly suppressed by UVI3003 (a RXR antagonist), while enhanced by calcitriol (a VDR agonist). Additionally, the disruption of autophagy in the hippocampus of HFD mice was ameliorated by honokiol, which was attenuated by UVI3003 but strengthened by calcitriol. Taken together, the data provide new evidence that honokiol exerts the antidepressant-like effect in HFD diabetic mice via activating RXR/VDR heterodimer to restore the balance of autophagy. Our findings indicate that the RXR/VDR-mediated signaling might be a potential target for treating diabetes with comorbid depression.

Cluster-Triggered Self-Luminescence, Rapid Self-Healing, and Adaptive Reprogramming Liquid Crystal Elastomers Enabled by Dynamic Imine Bond.

The integration of advanced functions and diverse practical applications calls for multifunctional liquid crystal elastomers (LCEs); however, the structure-intrinsic luminescence and excellent mechanical properties of LCEs have not yet been explored. In this study, clusteroluminescence (CL)-based LCEs (CL-LCEs) are successfully fabricated without depending on large conjugated structures, thereby avoiding redundant organic synthesis and aggregation-caused quenching. The experimental and theoretical results reveal that secondary amine (-NH-) and imine (-C = N-) groups play vital roles in determining the presence of fluorescence in CL-LCEs. Based on the above observation, the strategy universalization and a molecular library for constructing CL-LCEs are further demonstrated. Meanwhile, the dynamic bond of imine bonds endows the CL-LCE system with rapid self-healing under mild conditions (70 °C in 10 min), excellent stretchability, and adaptive programmable characteristics. Furthermore, the self-luminescent performance enables visual detection of the self-healing process. Finally, CL-based information storage and anticounterfeiting are successfully realized and their applications in fiber actuators and fluorescent textiles are demonstrated. The distinctive luminescence and dynamic chemistry presented in this work has significant implications in elucidating the mechanism of CL and providing new strategies for the rational design of novel multifunctional LCE materials.

Interactive model for predicting the oncological outcome of patients with early-stage huge hepatocellular carcinoma after hepatectomy: a multicenter population-based study.

An interactive model for predicting the oncological outcome of patients with early-stage huge hepatocellular carcinoma (ES-HHCC) after hepatectomy is still lacking. This study was aimed at exploring the independent risk parameters and developing an interactive model for predicting the cancer-specific survival (CSS) of ES-HHCC. Data from patients with ES-HHCC who underwent hepatectomy were collected. The dimensionality of the clinical features was reduced by least absolute shrinkage and selection operator regression and further screened as predictors of CSS by Cox regression. Then, an interactive prediction model was developed and validated. Among the 514 screened patients, 311 and 203 of them were assigned into the training and validation cohort, respectively. Six independent variables, including alpha-fetoprotein, cirrhosis, microvascular invasion, satellite, tumor morphology, and tumor diameter, were identified and incorporated into the prediction model for CSS. The model achieved C-indices of 0.724 and 0.711 in the training and validation cohorts, respectively. Calibration curves showed general consistency in both cohorts. Compared with single predictor, the model had a better performance and greater benefit according to the time-independent receiver operating characteristic curve and decision curve analysis (P < 0.05). The calculator owned satisfactory accuracy and flexible operability for predicting the CSS of ES-HHCC, which could serve as a practical tool to stratify patients with different risks, and guide decision-making.

Genome-wide analysis of LOG family genes in castor and RcLOG5 enhances drought, salt, and cold stress tolerance in Arabidopsis thaliana.

The gene encoding the specific phosphohydrolase LONELY GUY (LOG) plays an important role in the activation of cytokinin and the stress response in plant cells. However, the role of LOG genes in castor bean (Ricinus communis) has not been reported. In this study, we identified a total of nine members of the LOG gene family in the castor bean genome and investigated the upregulated expression of the RcLOG5 gene using transcriptome data analysis. We found that the RcLOG5 gene exhibited tissue-specific expression and was activated by polyethylene glycol, NaCl, low temperature, and abscisic acid stress. The subcellular localization results showed that the RcLOG5 gene is mainly located in the cytoplasm. Based on phenotypic and physiological indicators, namely root length, peroxidase activity, and malondialdehyde content, overexpression of the RcLOG5 gene not only improved the drought resistance, salt tolerance, and cold tolerance of transgenic Arabidopsis, but also shortened the dormancy period of the transgenic plants. Transcriptomic sequencing revealed that the overexpression of the RcLOG5 gene led to the enrichment of differentially expressed genes in the glutathione metabolism pathway in transgenic Arabidopsis. Moreover, the overexpression plants had higher levels of glutathione and a higher GSH/GSSG ratio under stress compared to the wild type. Therefore, we inferred that the RcLOG5 gene may be responsible for regulating cell membrane homeostasis by reducing the accumulation of reactive oxygen species through the glutathione pathway. Overall, the overexpression of the RcLOG5 gene positively regulated the stress resistance of transgenic Arabidopsis. This study provides valuable gene resources for breeding stress-tolerant castor bean varieties.

The potential role of the triglyceride-glucose index in left ventricular systolic function and in-hospital outcomes for patients with acute myocardial infarction.

BACKGROUND: A limited number of small-sample cohort studies have investigated the association between the triglyceride-glucose index and in-hospital prognosis. Moreover, the translational potential role of left ventricular systolic function - measured by left ventricular ejection fraction - combined with the triglyceride-glucose index in prioritizing patients with acute myocardial infarction at high risk of in-hospital major adverse cardiovascular events remains unknown. AIM: To explore the potential role of the triglyceride-glucose index in left ventricular systolic function and in-hospital major adverse cardiovascular events in patients with acute myocardial infarction. METHODS: The Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project (CCC-ACS) was analysed for this study. RESULTS: We included 43,796 patients with acute myocardial infarction. Patients with a higher triglyceride-glucose index showed an increased risk of major adverse cardiovascular events (adjusted odds ratio 1.46, 95% confidence interval 1.31-1.63). Interaction analyses revealed that left ventricular ejection fraction modified the relationship between the triglyceride-glucose index and major adverse cardiovascular events. Furthermore, patients with acute myocardial infarction were categorized by the triglyceride-glucose index and left ventricular ejection fraction; the low left ventricular ejection fraction/high triglyceride-glucose index group showed the highest risk of major adverse cardiovascular events (adjusted odds ratio 2.14, 95% confidence interval 1.58-2.89). CONCLUSIONS: In a comprehensive nationwide acute myocardial infarction registry conducted in China, a higher triglyceride-glucose index was found to be associated with in-hospital major adverse cardiovascular events, and this was particularly evident among patients with a lower left ventricular ejection fraction. Moreover, the triglyceride-glucose index combined with left ventricular ejection fraction was helpful for risk stratification of patients with acute myocardial infarction.

Green Starch-Based Hydrogels with Excellent Injectability, Self-Healing, Adhesion, Photothermal Effect, and Antibacterial Activity for Promoting Wound Healing.

Hydrogel materials have proven valuable in wound healing, but improving the safety of these hydrogels is still challenging. Therefore, designing multifunctional natural polymeric-based hydrogels with excellent mechanical properties to replace toxic or potentially risky, refractory chemical polymer-based hydrogels such as polyacrylamide and polyethylene glycol is of particular significance. Here, a green starch-based hydrogel (Starch@Ca/CGC hydrogel) with injectability, self-healing, and instant adhesion was constructed by coordination interaction, electrostatic interaction, and intramolecular and intermolecular hydrogen bonds. Therein, natural bioactive small molecules gallic acid (GA) and carvacrol (CA) were coordinated with metal ions by the ultrasonic-triggered self-assembly and ionic cross-linking codriven strategy to prepare Cu-gallic acid-carvacrol nanospheres (CGC NPs), which conferred the hydrogel with near-infrared light (NIR)-controlled CA release and photothermal synergistic sterilization properties, as well as antioxidant and anti-infection capabilities. More importantly, the multifunctional hydrogel platforms could completely cover an irregular wound shape to prevent secondary injury and significantly accelerate wound healing under NIR with more skin appendages like hair follicles and blood vessels appearing. Therefore, it is expected that this starch-based hydrogel could serve as a competitive multifunctional dressing in the biomedical field, including bacteria-derived wound infection and other tissue repair.

Split-Type Magnetic Soft Tactile Sensor with 3D Force Decoupling.

Tactile sensory organs for sensing 3D force, such as human skin and fish lateral lines, are indispensable for organisms. With their sensory properties enhanced by layered structures, typical sensory organs can achieve excellent perception as well as protection under frequent mechanical contact. Here, inspired by these layered structures, a split-type magnetic soft tactile sensor with wireless 3D force sensing and a high accuracy (1.33%) fabricated by developing a centripetal magnetization arrangement and theoretical decoupling model is introduced. The 3D force decoupling capability enables it to achieve a perception close to that of human skin in multiple dimensions without complex calibration. Benefiting from the 3D force decoupling capability and split design with a long effective distance (>20 mm), several sensors are assembled in air and water to achieve delicate robotic operation and water flow-based navigation with an offset <1.03%, illustrating the extensive potential of magnetic tactile sensors in flexible electronics, human-machine interactions, and bionic robots.

Response inhibition impairment related to altered frontal-striatal functional connectivity in insomnia disorder: A pilot and non-clinical study.

BACKGROUND: It is not clear whether and how insomnia disorder (ID) impairs response inhibition ability. Fronto-striatal functional connectivity (FC) plays a critical role in response inhibition and is found be abnormal in patients with ID. In this study, we examined whether insomnia symptoms impair response inhibition in a large non-clinical sample and whether impaired response inhibition is related to abnormal fronto-striatal FC. METHODS: One hundred and fifteen young ID patients and 160 age and sex-matched healthy controls (HC) underwent resting-state functional magnetic response imaging scans and performed the stop-signal task (SST). Performance of SST, Gray Matter Volumes (GMVs), and connections of brain regions related to fronto-striatal circuits was compared between groups. Further examined the association between response inhibition impairment and fronto-striatal FC. RESULTS: The behavioral results showed that patients with ID had significantly longer stop-signal reaction time (SSRT) compared with the HC, reflecting the impaired response inhibition among IDs. Brain imaging results showed IDs had decreased GMVs of the Right Superior Frontal (SFG) and left Supplementary Motor area (SMA). Seed-based FC results showed that compared to HC, the ID showed decreased FC between left SMA and left Paracentral lobule, left SMA and right SMA, and right SFG and right Orbital Middle Frontal gyrus, and increased FC between right SFG and right putamen. Meanwhile, the FC between right SFG and putamen was positively correlated with SSRT in IDs. CONCLUSIONS: The current study found significantly impaired response inhibition among ID and this impairment may be related to abnormal fronto-striatal FC in ID.

Arecoline-Induced Hepatotoxicity in Rats: Screening of Abnormal Metabolic Markers and Potential Mechanisms.

Arecoline is a pyridine alkaloid derived from areca nut in the Arecaceae family. It has extensive medicinal activity, such as analgesic, anti-inflammatory, and anti-allergic. However, the toxicity of Arecoline limits its application. Most current studies on its toxicity mainly focus on immunotoxicity, carcinogenesis, and cancer promotion. However, there are few systematic studies on its hepatotoxicity and mechanisms. Therefore, this research explored the mechanism of hepatotoxicity induced by Arecoline in rats and analyzed endogenous metabolite changes in rat plasma by combining network toxicology with metabolomics. The differential metabolites after Arecoline exposure, such as D-Lysine, N4-Acetylaminobutanal, and L-Arginine, were obtained by metabolomics study, and these differential metabolites were involved in the regulation of lipid metabolism, amino acid metabolism, and vitamin metabolism. Based on the strategy of network toxicology, Arecoline can affect the HIF-1 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, and other concerning pathways by regulating critical targets, such as ALB, CASP3, EGFR, and MMP9. Integration of metabolomics and network toxicology results were further analyzed, and it was concluded that Arecoline may induce hepatotoxicity by mediating oxidative stress, inflammatory response, energy and lipid metabolism, and cell apoptosis.

An AI Dietitian for Type 2 Diabetes Mellitus Management Based on Large Language and Image Recognition Models: Preclinical Concept Validation Study.

BACKGROUND: Nutritional management for patients with diabetes in China is a significant challenge due to the low supply of registered clinical dietitians. To address this, an artificial intelligence (AI)-based nutritionist program that uses advanced language and image recognition models was created. This program can identify ingredients from images of a patient's meal and offer nutritional guidance and dietary recommendations. OBJECTIVE: The primary objective of this study is to evaluate the competence of the models that support this program. METHODS: The potential of an AI nutritionist program for patients with type 2 diabetes mellitus (T2DM) was evaluated through a multistep process. First, a survey was conducted among patients with T2DM and endocrinologists to identify knowledge gaps in dietary practices. ChatGPT and GPT 4.0 were then tested through the Chinese Registered Dietitian Examination to assess their proficiency in providing evidence-based dietary advice. ChatGPT's responses to common questions about medical nutrition therapy were compared with expert responses by professional dietitians to evaluate its proficiency. The model's food recommendations were scrutinized for consistency with expert advice. A deep learning-based image recognition model was developed for food identification at the ingredient level, and its performance was compared with existing models. Finally, a user-friendly app was developed, integrating the capabilities of language and image recognition models to potentially improve care for patients with T2DM. RESULTS: Most patients (182/206, 88.4%) demanded more immediate and comprehensive nutritional management and education. Both ChatGPT and GPT 4.0 passed the Chinese Registered Dietitian examination. ChatGPT's food recommendations were mainly in line with best practices, except for certain foods like root vegetables and dry beans. Professional dietitians' reviews of ChatGPT's responses to common questions were largely positive, with 162 out of 168 providing favorable reviews. The multilabel image recognition model evaluation showed that the Dino V2 model achieved an average F1 score of 0.825, indicating high accuracy in recognizing ingredients. CONCLUSIONS: The model evaluations were promising. The AI-based nutritionist program is now ready for a supervised pilot study.

Destriping of Remote Sensing Images by an Optimized Variational Model.

Satellite sensors often capture remote sensing images that contain various types of stripe noise. The presence of these stripes significantly reduces the quality of the remote images and severely affects their subsequent applications in other fields. Despite the existence of many stripe noise removal methods in the research, they often result in the loss of fine details during the destriping process, and some methods even generate artifacts. In this paper, we proposed a new unidirectional variational model to remove horizontal stripe noise. The proposed model fully considered the directional characteristics and structural sparsity of the stripe noise, as well as the prior features of the underlying image, to design different sparse constraints, and the ℓp quasinorm was introduced in these constraints to better describe these sparse characteristics, thus achieving a more excellent destriping effect. Moreover, we employed the fast alternating direction method of multipliers (ADMM) to solve the proposed non-convex model. This significantly improved the efficiency and robustness of the proposed method. The qualitative and quantitative results from simulated and real data experiments confirm that our method outperforms existing destriping approaches in terms of stripe noise removal and preservation of image details.

Patterns of Circulating Microbiota during the Acute Phase Following ST-Segment Elevation Myocardial Infarction Predict Long-Term Cardiovascular Events.

Limited information exists regarding whether circulating microbiota could predict long-term clinical outcomes following ST-segment elevation myocardial infarction (STEMI). A total of 244 consecutive patients with STEMI were followed for 2.8 years, and 64 first major adverse cardiovascular events (MACEs) were recorded. Both microbiota abundance [Corynebacterium tuberculostearicum (HR, 1.28; 95% CI, 1.03-1.58) and Staphylococcus aureus (S. aureus) (HR, 1.16; 95% CI, 1.02-1.33) ] and microbiota clusters (Cluster 2 versus Cluster 1: HR, 1.84; 95% CI, 1.04-3.27) could independently predict MACE. Furthermore, a model based on established independent predictors alone was significantly improved by the addition of different microbiota patterns. In addition, CD14++CD16+ monocytes (Mon2) had a significant mediation effect on the microbiota patterns → MACE association. The present study demonstrated that the abundance and clusters of circulating microbiota are associated with future adverse cardiovascular events independent of traditional risk factors, which were partially mediated by an increase in Mon2.

Subtypes of insomnia revealed by the heterogeneity of neuroanatomical patterns: A structural MRI study.

The current conflicting neuroimaging findings of insomnia disorder (ID) may be attributed to heterogeneity in ID. The present study aims to clarify the high heterogeneity in ID and examine the objective neurobiological subtypes of ID by using a novel machine learning method based on gray matter volumes (GMVs). We recruited 56 patients with ID and 73 healthy controls (HCs). The T1-weighted anatomical images were obtained for each participant. We investigated whether the ID has higher interindividual heterogeneity in GMVs. Then, we used a heterogeneous machine learning algorithm by discriminative analysis (HYDRA) to identify subtypes of ID with features of brain regional GMVs. We found that patients with ID have higher interindividual variability than HCs. HYDRA identified two distinct and reliable neuroanatomical subtypes of ID. Two subtypes showed significantly different aberrance in GMVs compared with HCs. Specifically, subtype 1 exhibited widespread decreased GMVs in some brain regions, including the right inferior temporal gyrus, left superior temporal gyrus, left precuneus, right middle cingulate, and right supplementary motor area. Subtype 2 only demonstrated increased GMVs in the right superior temporal gyrus. Additionally, the GMVs of altered brain regions in subtype 1 were significantly correlated with daytime functioning, but in subtype 2, they were significantly correlated with sleep disturbance. These results explain conflicting neuroimaging findings and propose a potential objective neurobiological classification contributing to ID's precise clinical diagnosis and treatment.

Synergistic role of circulating CD14++CD16+ monocytes and fibrinogen in predicting the cardiovascular events after myocardial infarction.

BACKGROUND: Monocytes and fibrinogen (FIB) play important roles in driving acute and reparative inflammatory pathways after myocardial infarction (MI). In humans, there are three subsets of monocytes, namely, CD14++CD16- (Mon1), CD14++CD16+ (Mon2), and CD14+CD16++ (Mon3). During the inflammatory response, monocyte subsets express high levels of integrin αM ß2 and protease-activated receptors 1 and 3 to interact with FIB. HYPOTHESIS: However, whether there is a synergistic role of FIB combined with Mon2 counts in prioritizing patients at high risk of future major adverse cardiovascular events (MACEs) after MI remains unknown. METHODS: The MI patients who treated with primary percutaneous coronary intervention were enrolled. MI patients were categorized into four groups, that is, low FIB/low Mon2, low FIB/high Mon2, high FIB/low Mon2, and high FIB/high Mon2, according to cutoff values of 3.28 g/L for FIB and 32.20 cells/µL for Mon2. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the risk of MACEs of MI patients during a median follow-up of 2.7 years. Mediating effects of high FIB levels and MACEs associated with high monocyte subsets were calculated by mediation analysis. RESULTS: High FIB/high Mon2 group had the highest risk of MACEs during a median follow-up of 2.7 years. Moreover, mediation analysis showed that a high FIB level could explain 24.9% (p < .05) of the increased risk of MACEs associated with Mon2. CONCLUSION: This work provides evidence indicating the translational potential of a synergistic role of FIB combined with Mon2 in prioritizing patients at high risk of future MACEs after MI.

Evaluation of Physicochemical Properties of Sustained-Release Membranes Based on Analytic Hierarchy.

In this paper, the optimal analytic hierarchy process was used to establish a comprehensive evaluation model for the physicochemical properties of composite sustained-release membrane materials based on water absorption (XS), water permeability (TS), tensile strength (KL), elongation at break (DSL), fertilizer permeability (TF), and viscosity (ND), and the optimal ratio parameters of membrane material were determined. Analytic hierarchy process (AHP) combined with correlation analysis was used to construct the judgment matrix of physicochemical properties, which passed the consistency test, and to determine the weight and ranking of each index: TF (0.6144) > XS (0.1773) > KL (0.1561) > ND (0.1311) > TS (0.0775) > DSL (0.0520). The comprehensive scores of sustained-release membrane materials under different treatments were calculated based on normalized data samples and weights. It was determined that the percentage of each component in the best comprehensive performance of the slow-release membrane material was as follows: polyvinyl alcohol, polyvinylpyrrolidone, zeolite, and epoxy resin were 7.3%, 0.7%, 0.5%, and 2%, respectively.

Spatial metabolomics reveal mechanisms of dexamethasone against pediatric pneumonia.

Currently, drugs are limited to treating pediatric pneumonia in clinical practice. It is urgent to find one new precise prevention and control therapy. The dynamically changing biomarkers during the development of pediatric pneumonia could help diagnose this disease, determine its severity, assess the risk of future events, and guide its treatment. Dexamethasone has been recognized as an effective agent with anti-inflammatory activity. However, its mechanisms against pediatric pneumonia remain unclear. In this study, spatial metabolomics was used to reveal the potential and characteristics of dexamethasone. Specifically, bioinformatics was first applied to find the critical biomarkers of differential expression in pediatric pneumonia. Subsequently, Desorption Electrospray Ionization mass spectrometry imaging-based metabolomics screened the differential metabolites affected by dexamethasone. Then, a gene-metabolite interaction network was built to mark functional correlation pathways for exploring integrated information and core biomarkers related to the pathogenesis and etiology of pediatric pneumonia. Further, these were validated by molecular biology and targeted metabolomics. As a result, genes of Cluster of Differentiation19, Fc fragment of IgG receptor IIb, Cluster of Differentiation 22, B-cell linker, Cluster of Differentiation 79B and metabolites of Triethanolamine, Lysophosphatidylcholine(18:1(9Z)), Phosphatidylcholine(16:0/16:0), phosphatidylethanolamine(O-18:1(1Z)/20:4(5Z,8Z,11Z,14Z)) were identified as the critical biomarkers in pediatric pneumonia. B cell receptor signaling pathway and glycerophospholipid metabolism were integrally analyzed as the main pathways of these biomarkers. The above data were illustrated using a Lipopolysaccharides-induced lung injury juvenile rat model. This work will provide evidence for the precise treatment of pediatric pneumonia.

Protocol for high-throughput single-cell patterning using a reusable ultrathin metal microstencil.

Exploiting convenient strategies for single-cell preparation while maintaining a high throughput remains challenging. This protocol describes a simple workflow for high-throughput single-cell patterning using a reusable ultrathin metal microstencil (UTmS). We describe UTmS-chip design, fabrication, and quality characterization. We then detail the preparation of flat substrates and chip assembly for single-cell patterning, followed by culturing of cells on a chip. Finally, we describe the evaluation of single-cell patterning and the downstream applications for studying single-cell calcium release and apoptosis. For complete details on the use and execution of this protocol, please refer to Song et al. (2021).1.

Renin-angiotensin system inhibition and in-hospital mortality in acute coronary syndrome patients with advanced renal dysfunction: findings from CCC-ACS project and a nationwide electronic health record-based cohort in China.

AIMS: In acute coronary syndrome (ACS) patients without advanced renal dysfunction [estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2], early (within 24 h of admission) angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) is the guideline-directed medical therapy. The clinical efficacy of early ACEI/ARB therapy among ACS patients with advanced renal dysfunction remains unclear. METHODS AND RESULTS: Among 184 850 ACS patients hospitalized from July 2014 to December 2018 in the Chinese National Electronic Disease Surveillance System Platform (CNEDSSP) cohort and 113 650 ACS patients enrolled from November 2014 to December 2019 in the Improving Care for Cardiovascular Disease in China-ACS Project (CCC-ACS) cohort, we identified 3288 and 3916 ACS patients with admission eGFR < 30 mL/min/1.73 m2 [2647 patients treated with ACEI/ARB (36.7%)], respectively. After 1:1 propensity score matching (PSM) in each cohort, Kaplan-Meier analysis showed that early ACEI/ARB use was associated with a 39% [hazard ratio (HR): 0.61, 95% confidence interval (95% CI): 0.45-0.82] and a 34% (HR: 0.66, 95% CI: 0.46-0.95) reduction in in-hospital mortality in CNEDSSP and CCC-ACS cohorts, respectively, which was consistent in multiple sensitivity analyses. A random effect meta-analysis of the two cohorts after PSM revealed a 32% reduction (risk ratio: 0.68, 95% CI: 0.55-0.84) in in-hospital mortality among ACEI/ARB users. CONCLUSIONS: Based on two nationwide cohorts in China in contemporary practice, we demonstrated that ACEI/ARB therapy initiated within 24 h of admission is associated with a reduction in in-hospital mortality in ACS patients with advanced renal dysfunction. CLINICAL TRIAL REGISTRATION: CCC-ACS project was registered at URL: https://www.clinicaltrials.gov. (Unique identifier: NCT02306616).