Five-year follow-up of OCT-guided percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Compared with intravascular ultrasound guidance, there is limited evidence for optical coherence tomography (OCT) guidance during primary percutaneous coronary intervention (pPCI) in ST-segment elevation myocardial infarction (STEMI) patients. AIMS: We investigated the role of OCT in guiding a reperfusion strategy and improving the long-term prognosis of STEMI patients. METHODS: All patients who were diagnosed with STEMI and who underwent pPCI between January 2017 and December 2020 were enrolled and divided into OCT-guided versus angiography-guided cohorts. They had routine follow-up for up to 5 years or until the time of the last known contact. All-cause death and cardiovascular death were designated as the primary and secondary endpoints, respectively. RESULTS: A total of 3,897 patients were enrolled: 2,696 (69.2%) with OCT guidance and 1,201 (30.8%) with angiographic guidance. Patients in the OCT-guided cohort were less often treated with stenting during pPCI (62.6% vs 80.2%; p<0.001). The 5-year cumulative rates of all-cause mortality and cardiovascular mortality in the OCT-guided cohort were 10.4% and 8.0%, respectively, significantly lower than in the angiography-guided cohort (19.0% and 14.1%; both log-rank p<0.001). All 4 multivariate models showed that OCT guidance could significantly reduce 5-year all-cause mortality (hazard ratio [HR] in model 4: 0.689, 95% confidence interval [CI]: 0.551-0.862) and cardiovascular mortality (HR in model 4: 0.692, 95% CI: 0.536-0.895). After propensity score matching, the benefits of OCT guidance were consistent in terms of all-cause mortality (HR: 0.707, 95% CI: 0.548-0.913) and cardiovascular mortality (HR: 0.709, 95% CI: 0.526-0.955). CONCLUSIONS: Compared with angiography alone, OCT guidance may change reperfusion strategies and lead to better long-term survival in STEMI patients undergoing pPCI. Findings in the current observational study should be further corroborated in randomised trials.

Comprehensive evaluation of "Three Waters" carrying capacity and path evolution study: A case of the Yellow River Basin.

Research focusing solely on the carrying capacity of a single aspect of water resources, water environment, or water ecology is no longer sufficient to support the sustainable development and management of basin water systems. The study of basin carrying capacity should expand towards a comprehensive and holistic direction. Therefore, this study constructed an evaluation index system for carrying capacity based on water resources, water environment, and water ecology ("Three Waters"). Utilizing the entropy weight-TOPSIS method, System Comprehensive Index Evaluation, and ArcGIS tools, the comprehensive evaluation index of the "Three Waters" System Carrying Capacity (TWSCC) in the Yellow River Basin (YRB) from 2005 to 2020 was calculated. The evaluation index analyzed the spatiotemporal variation characteristics of subsystem carrying capacity and performed early warning identification and analysis of TWSCC. Four differentiated developmental pathways were designed based on the current status of basin carrying capacity. Leveraging System Dynamics (SD) modeling, the dynamic simulation, and emulation of carrying capacity trends in the YRB from 2020 to 2035 were conducted. The research findings indicate that from 2005 to 2020, the TWSCC levels across the nine provinces in the YRB consistently exhibited varying degrees of overload. The alert levels mostly remained in "Heavy warning" or "Medium warning" states. By 2035, TWSCC under the four development paths improved from 2020 levels, with the Green Environmental Protection-Oriented scheme reaching a safe carrying capacity. In summary, this paper offers theoretical and methodological support for developing basin-carrying capacity and the integrated governance of "Three Waters."

Soft Crawling Microrobot Based on Flexible Optoelectronics Enabling Autonomous Phototaxis in Terrestrial and Aquatic Environments.

Many organisms move directly toward light for prey hunting or navigation, which is called phototaxis. Mimicking this behavior in robots is crucially important in the energy industry and environmental exploration. However, the phototaxis robots with rigid bodies and sensors still face challenges in adapting to unstructured environments, and the soft phototaxis robots often have high requirements for light sources with limited locomotion performance. Here, we report a 3.5 g soft microrobot that can perceive the azimuth angle of light sources and exhibit rapid phototaxis locomotion autonomously enabled by three-dimensional flexible optoelectronics and compliant shape memory alloy (SMA) actuators. The optoelectronics is assembled from a planar patterned flexible circuit with miniature photodetectors, introducing the self-occlusion to light, resulting in high sensing ability (error < 3.5°) compared with the planar counterpart. The actuator produces a straightening motion driven by an SMA wire and is then returned to a curled shape by a prestretched elastomer layer. The actuator exhibits rapid actuation within 0.1 s, a significant degree of deformation (curvature change of ∼87 m-1) and a blocking force of ∼0.4 N, which is 68 times its own weight. Finally, we demonstrated the robot is capable of autonomously crawling toward a moving light source in a hybrid aquatic-terrestrial environment without human intervention. We envision that our microrobot could be widely used in autonomous light tracking applications.

The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) as a predictor of all-cause and cardiovascular mortality in US adults with diabetes or prediabetes: NHANES 1999-2018.

BACKGROUND: The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) serves as a novel composite lipid indicator for atherosclerosis. However, the association between NHHR and mortality in patients with diabetes or prediabetes remains unclear. Consequently, the objective of this study was to investigate the relationship between NHHR and both all-cause and cardiovascular mortality in US adults with diabetes or prediabetes. METHODS: This study included 12,578 adult participants with diabetes or prediabetes from the US National Health and Nutrition Examination Survey (1999-2018). Mortality outcomes were ascertained by linking to the National Death Index (NDI) record up to December 31, 2019. We employed a weighted multivariate Cox proportional hazards model and restricted cubic splines to assess the associations between NHHR and all-cause and cardiovascular mortality. A segmented Cox proportional hazards model was used for evaluating threshold effects. Furthermore, a competing risks analysis was performed to explore the relationship between NHHR and cardiovascular mortality. RESULTS: During a median follow-up period of 8.08 years, 2403 participants encountered all-cause mortality, with 662 of them specifically succumbing to cardiovascular mortality. The restricted cubic splines revealed a U-shaped association between NHHR and all-cause mortality, while an L-shaped association was observed for cardiovascular mortality. The analysis of threshold effects revealed that the inflection points for NHHR and all-cause and cardiovascular mortality were 2.72 and 2.83, respectively. Specifically, when the baseline NHHR was below the inflection points, a negative correlation was observed between NHHR and both all-cause mortality (HR: 0.76, 95% CI: 0.68-0.85) and cardiovascular mortality (HR: 0.70, 95% CI: 0.57-0.85). Conversely, when the baseline NHHR exceeded the inflection points, a positive correlation was observed between NHHR and both all-cause mortality (HR: 1.11, 95% CI: 1.06-1.16) and cardiovascular mortality (HR: 1.08, 95% CI: 1.00-1.16). CONCLUSIONS: Among US adults with diabetes or prediabetes, a U-shaped association was observed between NHHR and all-cause mortality, whereas an L-shaped association was identified with cardiovascular mortality. The inflection points for all-cause and cardiovascular mortality were 2.72 and 2.83, respectively.

RT-RPA-PfAgo detection platform for one-tube simultaneous typing diagnosis of human respiratory syncytial virus.

Human respiratory syncytial virus (HRSV) is the most prevalent pathogen contributing to acute respiratory tract infections (ARTI) in infants and young children and can lead to significant financial and medical costs. Here, we developed a simultaneous, dual-gene and ultrasensitive detection system for typing HRSV within 60 minutes that needs only minimum laboratory support. Briefly, multiplex integrating reverse transcription-recombinase polymerase amplification (RT-RPA) was performed with viral RNA extracted from nasopharyngeal swabs as a template for the amplification of the specific regions of subtypes A (HRSVA) and B (HRSVB) of HRSV. Next, the Pyrococcus furiosus Argonaute (PfAgo) protein utilizes small 5'-phosphorylated DNA guides to cleave target sequences and produce fluorophore signals (FAM and ROX). Compared with the traditional gold standard (RT-qPCR) and direct immunofluorescence assay (DFA), this method has the additional advantages of easy operation, efficiency and sensitivity, with a limit of detection (LOD) of 1 copy/µL. In terms of clinical sample validation, the diagnostic accuracy of the method for determining the HRSVA and HRSVB infection was greater than 95%. This technique provides a reliable point-of-care (POC) testing for the diagnosis of HRSV-induced ARTI in children and for outbreak management, especially in resource-limited settings.

AI driven analysis of MRI to measure health and disease progression in FSHD.

Facioscapulohumeral muscular dystrophy (FSHD) affects roughly 1 in 7500 individuals. While at the population level there is a general pattern of affected muscles, there is substantial heterogeneity in muscle expression across- and within-patients. There can also be substantial variation in the pattern of fat and water signal intensity within a single muscle. While quantifying individual muscles across their full length using magnetic resonance imaging (MRI) represents the optimal approach to follow disease progression and evaluate therapeutic response, the ability to automate this process has been limited. The goal of this work was to develop and optimize an artificial intelligence-based image segmentation approach to comprehensively measure muscle volume, fat fraction, fat fraction distribution, and elevated short-tau inversion recovery signal in the musculature of patients with FSHD. Intra-rater, inter-rater, and scan-rescan analyses demonstrated that the developed methods are robust and precise. Representative cases and derived metrics of volume, cross-sectional area, and 3D pixel-maps demonstrate unique intramuscular patterns of disease. Future work focuses on leveraging these AI methods to include upper body output and aggregating individual muscle data across studies to determine best-fit models for characterizing progression and monitoring therapeutic modulation of MRI biomarkers.

Rhodamine and related substances in food: Recent updates on pretreatment and analysis methods.

Rhodamine, a colorant prohibited in various consumer products due to its demonstrated carcinogenic, mutagenic, and toxic properties, necessitates the development of a straightforward, efficient, sensitive, environmentally friendly, and cost-effective analytical method. This review provides an overview of recent advancements in the pretreatment and determination techniques for rhodamine across diverse sample matrices since 2017. Sample preparation methods encompass both commonly used pretreatment techniques such as filtration, centrifugation, solvent extraction, and cloud point extraction, as well as innovative approaches including solid phase extraction, dispersive liquid-liquid microextraction, hollow fiber liquid phase microextraction, magnetic solid phase extraction, and matrix solid phase dispersion. The analytical techniques encompass high performance liquid chromatography, surface-enhanced Raman scattering, and sensor-based methods. Furthermore, a comprehensive examination is conducted to offer insights for future research on rhodamine regarding the advantages, disadvantages, and advancements in various pretreatment and determination methodologies.

Overall survival associated with surgery, radiotherapy, and chemotherapy in metastatic vulvar cancer: A retrospective cohort study based on the SEER database.

Background: Large cancer registries help analyze the prognosis of rare malignancies, such as advanced vulvar cancer. This study aimed to compare the overall survival (OS) rates of patients with metastatic vulvar cancer who had undergone chemoradiotherapy and radiotherapy alone and identify prognostic factors using data from the Surveillance, Epidemiology, and End Results (SEER) registry. Methods: In this retrospective cohort study, we used the SEER database to identify patients with metastatic vulvar cancer diagnosed between 2000 and 2019. Propensity score matching was performed to balance the covariates. Kaplan-Meier curves and Cox models were used to analyze OS. Results: A total of 685 patients were included and divided into chemoradiotherapy and radiotherapy groups, and 400 patients were included after propensity score matching. The chemoradiotherapy group had higher OS in the matched cohort (hazard ratio [HR] = 0.7367; 95% confidence interval [CI]: 0.5906-0.9190; P = 0.0049) than the radiotherapy group, which was similar to that in the pre-matched cohort (P < 0.0001). Patients who had undergone surgery + radiotherapy with or without chemotherapy showed higher OS rates than those who had received radiotherapy with or without chemotherapy for patients aged <75 years and local tumor excision/destruction or surgical removal of the primary site was the recommended surgical choice (P < 0.05). Chemoradiotherapy is sufficient for patients ≥75 years of age. Conclusions: Patients with metastatic vulvar cancer should undergo surgery if they can tolerate it. Adjuvant chemoradiotherapy should be encouraged because this treatment modality was associated with higher OS than radiotherapy alone.

Designing Small Molecule PI3Kγ Inhibitors: A Review of Structure-Based Methods and Computational Approaches.

The PI3K/AKT/mTOR pathway plays critical roles in a wide array of biological processes. Phosphatidylinositol 3-kinase gamma (PI3Kγ), a class IB PI3K family member, represents a potential therapeutic opportunity for the treatment of cancer, inflammation, and autoimmunity. In this Perspective, we provide a comprehensive overview of the structure, biological function, and regulation of PI3Kγ. We also focus on the development of PI3Kγ inhibitors over the past decade and emphasize their binding modes, structure-activity relationships, and pharmacological activities. The application of computational technologies and artificial intelligence in the discovery of novel PI3Kγ inhibitors is also introduced. This review aims to provide a timely and updated overview on the strategies for targeting PI3Kγ.

Facile Synthesis of Ultra-Small Silver Nanoparticles Stabilized on Carbon Nanospheres for the Etherification of Silanes.

The dehydrocoupling reaction between alcohols and hydrosilanes is considered to be one of the most atom-economical ways to produce Si-O coupling compounds because its byproduct is only hydrogen (H2), which make it extremely environmentally friendly. In past decades, various kinds of homogeneous catalysts for the dehydrocoupling of alcohols and hydrosilanes, such as transition metal complexes, alkaline earth metals, alkali metals, and noble metal complexes, have been reported for their good activity and selectivity. Nevertheless, the practical applications of these catalysts still remain unsatisfactory, which is mainly restricted by environmental impact and non-reusability. A facile and recyclable heterogeneous catalyst, ultra-small Ag nanoparticles supported on porous carbon (Ag/C) for the etherification of silanes, has been developed. It has high catalytic activity for the Si-O coupling reaction, and the apparent activation energy of the reaction is about 30 kJ/mol. The ultra-small Ag nanoparticles dispersed in the catalyst through the carrier C have an enrichment effect on all reactants, which makes the reactants reach the adsorption saturation state on the surface of Ag nanoparticles, thus accelerating the coupling reaction process and verifying that the kinetics of the reaction of the catalyst indicate a zero-grade reaction.

Molecular quantification of herbs (Herb-Q): a pyrosequencing-based approach and its application in Pinellia ternata.

Variations in herb dosage due to species adulteration and dosing inaccuracies can substantially affect clinical safety and efficacy. Accurate species quantification remains challenging, as current methods often yield inconsistent results. This study introduces a novel pyrosequencing-based technique, termed herb molecular quantification (Herb-Q), designed to precisely quantify herbal products. We evaluated its effectiveness using Pinellia ternata and five of its adulterants. Initially, we assessed commonly used DNA barcodes with sequences from a public database, identifying two candidate regions, Maturase K (matK) and internal transcribed spacer 2 (ITS2), for screening specific single nucleotide polymorphism (SNP) loci, allowing for species-specific identification. These loci were validated by amplifying and sequencing genomic material from collected samples. Our validation studies showed that Herb-Q demonstrated excellent linearity, accuracy, repeatability, and detection limits. We established quantitative standard curves with high R2 values (> 0.99) to enable precise species quantification, which were combined with external standards to provide clear and accurate visual quantification results. The average bias in quantifying the tuber of P. ternata was 2.38%, confirming that Herb-Q can accurately identify and quantify herbal product constituents. Moreover, the entire quantification process took less than 4 h. This study presents a novel, rapid method for accurately quantifying species in herbal products and advances the application of DNA barcoding from species identification to quantitative detection.

Baduanjin for ischemic heart failure with mildly reduced/preserved ejection fraction (BEAR Trial): A randomized controlled trial.

AIM: While Baduanjin, a traditional Chinese mind-body exercise, has shown potential health benefits, its efficacy in improving outcomes for heart failure patients with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) has not been well documented. We aimed to investigate the adjunctive impact of Baduanjin on exercise capacity and quality of life for HFmrEF/HFpEF. METHODS: Patients with HFmrEF/HFpEF were enrolled in this multicenter randomized clinical trial. All participants were randomized to conventional cardiac rehabilitation with or without an additional 12-week Baduanjin exercise. The primary endpoint was the distance covered in a 6-min walk test (6MWD), while key secondary outcomes included quality of life measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and cardiopulmonary function including anaerobic threshold (VO2 AT). RESULTS: A total of 120 patients were enrolled, and 109 completed all session and tests. The mean age of the 120 patients was 60.5 years (SD, 9.21 years), and 23 (19.2%) were women. The Baduanjin group exhibited a 6.14% improvement in 6MWD compared to a 1.32% improvement in the control group (median improvement, 25.0 vs. 5.0 m; p < 0.001) at 12th week. The VO2 AT increased by 25.87% in the Baduanjin group versus 3.94% in the control group (p < 0.001). Quality of life also significantly improved in the Baduanjin group as indicated by MLHFQ score changes (-16.8% vs. -3.99%; p < 0.001). CONCLUSIONS: Adding Baduanjin to exercise-based cardiac rehabilitation for patients with ischemic HFmrEF or HFpEF are generally safe and could provide significant improvements in exercise capacity and quality of life.

Efficient segmentation of fetal brain MRI based on the physical resolution.

BACKGROUND: The image resolution of fetal brain magnetic resonance imaging (MRI) is a critical factor in brain development measures, which is mainly determined by the physical resolution configured in the MRI sequence. However, fetal brain MRI are commonly reconstructed to 3D images with a higher apparent resolution, compared to the original physical resolution. PURPOSE: This work is to demonstrate that accurate segmentation can be achieved based on the MRI physical resolution, and the high apparent resolution segmentation can be achieved by a simple deep learning module. METHODS: This retrospective study included 150 adult and 80 fetal brain MRIs. The adult brain MRIs were acquired at a high physical resolution, which were downsampled to visualize and quantify its impacts on the segmentation accuracy. The physical resolution of fetal images was estimated based on MRI acquisition settings and the images were downsampled accordingly before segmentation and restored using multiple upsampling strategies. Segmentation accuracy of ConvNet models were evaluated on the original and downsampled images. Dice coefficients were calculated, and compared to the original data. RESULTS: When the apparent resolution was higher than the physical resolution, the accuracy of fetal brain segmentation had negligible degradation (accuracy reduced by 0.26%, 1.1%, and 1.8% with downsampling factors of 4/3, 2, and 4 in each dimension, without significant differences from the original data). Using a downsampling factor of 4 in each dimension, the proposed method provided 7× smaller and 10× faster models. CONCLUSION: Efficient and accurate fetal brain segmentation models can be developed based on the physical resolution of MRI acquisitions.

Associations between the choroid plexus and tau in Alzheimer's disease using an active learning segmentation pipeline.

BACKGROUND: The cerebrospinal fluid (CSF), primarily generated by the choroid plexus (ChP), is the major carrier of the glymphatic system. The alternations of CSF production and the ChP can be associated with the Alzheimer's disease (AD). The present work investigated the roles of the ChP in the AD based on a proposed ChP image segmentation pipeline. METHODS: A human-in-the-loop ChP image segmentation pipeline was implemented with intermediate and active learning datasets. The performance of the proposed pipeline was evaluated on manual contours by five radiologists, compared to the FreeSurfer and FastSurfer toolboxes. The ChP volume and blood flow were investigated among AD groups. The correlations between the ChP volume and AD CSF biomarkers including phosphorylated tau (p-tau), total tau (t-tau), amyloid-ß42 (Aß42), and amyloid-ß40 (Aß40) was investigated using three models (univariate, multiple variables, and stepwise regression) on two datasets with 806 and 320 subjects. RESULTS: The proposed ChP segmentation pipeline achieved superior performance with a Dice coefficient of 0.620 on the test dataset, compared to the FreeSurfer (0.342) and FastSurfer (0.371). Significantly larger volumes (p < 0.001) and higher perfusion (p = 0.032) at the ChP were found in AD compared to CN groups. Significant correlations were found between the tau and the relative ChP volume (the ChP volume and ChP/parenchyma ratio) in each patient groups and in the univariate regression analysis (p < 0.001), the multiple regression model (p < 0.05 except for the t-tau in the LMCI), and in the step-wise regression model (p < 0.021). In addition, the correlation coefficients changed from - 0.32 to - 0.21 along with the AD progression in the multiple regression model. In contrast, the Aß42 and Aß40 shows consistent and significant associations with the lateral ventricle related measures in the step-wise regression model (p < 0.027). CONCLUSIONS: The proposed pipeline provided accurate ChP segmentation which revealed the associations between the ChP and tau level in the AD. The proposed pipeline is available on GitHub ( https://github.com/princeleeee/ChP-Seg ).

Women's experience of adopting lateral positions during the second stage of labour compared with conventional lithotomy positions: A cross-sectional study.

AIMS: Maternal positions during childbirth play an important role in safe vaginal births and might also influence women's childbirth experiences greatly. Lateral positions, as a potential position to reduce negative maternal and neonatal outcomes, have become popular in recent years, especially in China where the adoption of conventional lithotomy positions is still common. However, the childbirth experience of those who gave birth in lateral positions has been rarely studied. This study aimed to describe and compare women's childbirth experiences of adopting the newly introduced lateral positions and the conventional lithotomy positions during the second stage of labour. STUDY DESIGN: A cross-sectional study was conducted in two tertiary hospitals in China involving a total of 658 primiparous and parous women who adopted lateral and lithotomy positions during the second stage of labour from July to November 2020. Sociodemographic characteristics, maternal and neonatal outcomes as well as childbirth experience assessed by the Childbirth Experience Questionnaire (CEQ) were collected. This study followed the STROBE guidelines. RESULTS: Women who once adopted lateral positions during the second stage of labour had better positive childbirth experiences compared with those in the lithotomy positions group, as demonstrated by their overall higher CEQ scores. Women in the lateral position group also reported better participation and perceived safety, and a greater sense of control during childbirth. Lateral positions remained an influential factor in CEQ scores after controlling for potential confounders. In this study, adverse maternal and neonatal outcomes were rare. Women in lateral positions had comparatively better perineal outcomes. CONCLUSION: This study described and compared women's childbirth experiences of adopting conventional lithotomy positions and lateral positions during the second stage of labour using a valid instrument. Women who adopted lateral positions during the second stage of labour reported better childbirth experiences than those giving birth in the conventional lithotomy positions. Thus, assisting women in giving birth in lateral positions might be a promising way to improve women's childbirth experience.

miR-10167-3p targets TCF7L1 to inhibit bovine adipocyte differentiation and promote bovine adipocyte proliferation.

MicroRNAs (miRNAs) are widely involved in various lipogenic processes, including adipocyte proliferation and differentiation, lipid droplet formation, and adipocyte-specific gene activation. The present study aimed to investigate the gene expression profiles of bovine preadipocytes under high miR-10167-3p expression using the RNA-seq technique and to verify the functions of its downstream target genes on the proliferation and differentiation of bovine preadipocytes. First, RNA-seq identified 573 differentially expressed genes (DEGs), of which 243 were downregulated and 330 were upregulated. Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that 15.19% of the DEGs were enriched in pathways related to lipid metabolism. Meanwhile, dual-luciferase reporter gene assay verified the target-binding relationship between miR-10167-3p and TCF7L1. The function of TCF7L1 was assessed using several experiments in adipocytes with high TCF7L1 expression and RNA interference. The mRNA and protein expression of proliferation, differentiation, and apoptosis marker genes were detected using qPCR and western blot, respectively; lipid droplet synthesis was detected using oil red O, Nile red, and bodipy staining; adipocyte proliferation was detected by EdU; and apoptosis was detected using flow cytometry. The results revealed that TCF7L1 overexpression inhibited bovine preadipocyte differentiation and apoptosis and promoted their proliferation, with opposite results obtained with its RNA interference. These results may provide a reference for the subsequent investigation of the molecular mechanism of bovine fat deposition.

Huangqin tang alleviates colitis-associated colorectal cancer via amino acids homeostasisand PI3K/AKT/mtor pathway modulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Tang (HQT), a traditional Chinese medicine formula, is commonly used in clinical practice for the treatment of inflammatory bowel diseases. It has been reported that HQT exerts antitumor effects on colitis-associated colorectal cancer (CAC). However, the mechanism by which HQT interferes with the inflammation-to-cancer transformation remains unclear. AIMS OF THE STUDY: The purpose of this study was to dynamically evaluate the efficacy of HQT in alleviating or delaying CAC and to reveal the underlying mechanism. METHODS: We established a mouse model of CAC using azoxymethane combined with 1.5% dextran sodium sulphate. The efficacy of HQT was evaluated based on pathological sections and serum biochemical indices. Subsequently, amino acids (AAs) metabolism analyses were performed using ultra-performance liquid chromatography-tandem mass spectrometry, and the phosphatidylinositol 3 kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway was detected by western blotting. RESULTS: The data demonstrated that HQT could alleviate the development of CAC in the animal model. HQT effectively reduced the inflammatory response, particularly interleukin-6 (IL-6), in the inflammation induction stage, as well as in the stages of proliferation initiation and tumorigenesis. During the proliferation initiation and tumorigenesis stages, immunohistochemistry staining showed that the expression of the proliferation marker Ki67 was reduced, while apoptosis was increased in the HQT group. Accordingly, HQT substantially decreased the levels of specific AAs in the colon with CAC, including glutamic acid, glutamine, arginine, and isoleucine. Furthermore, HQT significantly inhibited the activated PI3K/AKT/mTOR pathway, which may contribute to suppression of cell proliferation and enhancement of apoptosis. CONCLUSION: HQT is effective in alleviating and delaying the colon "inflammation-to-cancer". The mechanism of action may involve HQT maintained AAs metabolism homeostasis and regulated PI3K/AKT/mTOR pathway, so as to maintain the balance between proliferation and apoptosis, and then interfere in the occurrence and development of CAC.

Metabolites from traditional Chinese botanical drugs with anti-hepatitis B virus activity - a review.

Hepatitis B virus (HBV)-related liver disease poses a major threat to human health worldwide. Although interferon and nucleoside analogues are commonly administered for treating chronic HBV infection, their use is limited by considerable side effects, drug resistance and incapacity for HBV elimination. Hence, novel HBV therapeutics are urgently required. For numerous years, traditional Chinese botanical drugs have been widely used to treat HBV-related diseases. The natural metabolites derived from these traditional drugs exhibit significant anti-HBV effects and serve as potential novel drugs for treating HBV. For overall understanding the therapeutic potential of these metabolites, the anti-HBV effects and mechanisms of action of 107 natural metabolites are summarized in this article. Mechanistically, these natural metabolites exert their anti-HBV effects by influencing the expression and function of host and/or viral genes, which differs from the mechanism of action of nucleoside analogues. Indeed, combining natural metabolites with nucleoside analogues can exert synergistic effects. Accordingly, natural metabolites or their chemically modified derivatives represent potential novel drugs and adjuvants for anti-HBV treatment.

Combining bioinformatics and multiomics strategies to investigate the key microbiota and active components of Liupao tea ameliorating hyperlipidemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperlipidemia as a major health issue has attracted much public attention. As a geographical indication product of China, Liupao tea (LPT) is a typical representative of traditional Chinese dark tea that has shown good potential in regulating glucose and lipid metabolism. LPT has important medicinal value in hyperlipidemia prevention. However, the active ingredients and metabolic mechanisms by which LPT alleviates hyperlipidemia remain unclear. AIM OF THE STUDY: This study aimed to systematically investigate the metabolic mechanisms and active ingredients of LPT extract in alleviating hyperlipidemia. MATERIALS AND METHODS: Firstly, we developed a mouse model of hyperlipidemia to study the pharmacodynamics of LPT. Subsequently, network pharmacology and molecular docking were performed to predict the potential key active ingredients and core targets of LPT against hyperlipidemia. LC-MS/MS was used to validate the identity of key active ingredients in LPT with chemical standards. Finally, the effect and metabolic mechanisms of LPT extract in alleviating hyperlipidemia were investigated by integrating metabolomic, lipidomic, and gut microbiome analyses. RESULTS: Results showed that LPT extract effectively improved hyperlipidemia by suppressing weight gain, remedying dysregulation of glucose and lipid metabolism, and reducing hepatic damage. Network pharmacology analysis and molecular docking suggested that four potential active ingredients and seven potential core targets were closely associated with roles for hyperlipidemia treatment. Ellagic acid, catechin, and naringenin were considered to be the key active ingredients of LPT alleviating hyperlipidemia. Additionally, LPT extract modulated the mRNA expression levels of Fxr, Cyp7a1, Cyp8b1, and Cyp27a1 associated with bile acid (BA) metabolism, mitigated the disturbances of BA and glycerophospholipid (GP) metabolism in hyperlipidemia mice. Combining fecal microbiota transplantation and correlation analysis, LPT extract effectively improved species diversity and abundance of gut microbiota, particularly the BA and GP metabolism-related gut microbiota, in the hyperlipidemia mice. CONCLUSIONS: LPT extract ameliorated hyperlipidemia by modulating GP and BA metabolism by regulating Lactobacillus and Dubosiella, thereby alleviating hyperlipidemia. Three active ingredients of LPT served as the key factors in exerting an improvement on hyperlipidemia. These findings provide new insights into the active ingredients and metabolic mechanisms of LPT in improving hyperlipidemia, suggesting that LPT can be used to prevent and therapeutic hyperlipidemia.

Effect of proton pump inhibitors versus histamine-2 receptor antagonists on acute kidney injury in septic patients at high risk for developing stress ulcers.

BACKGROUND: To compare the effects of proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) use on the occurrence of acute kidney injury (AKI) in septic patients at high risk for developing stress ulcers. METHODS: Using the Medical Information Mart for Intensive Care IV version 2.2 database, septic patients with high-risk factors for stress ulcers (i.e., shock, coagulopathy, invasive mechanical ventilation, or chronic liver diseases) were included. Exposures included PPIs and H2RAs within 24 h of intensive care unit (ICU) admission or prior to ICU admission. The primary end point was severe sepsis-associated AKI as defined by the Kidney Disease Improving Global Outcomes criteria stage 3 (KDIGO-3). Propensity score matching (PSM) was performed to balance baseline characteristics. Multivariable Cox proportional hazards regression was used to estimate the effect size. RESULTS: 4731 PPI users and 4903 H2RA users were included. After PSM, there were 1785 pairs exposed to PPIs and H2RAs. In the PSM cohort, the cumulative incident KDIGO-3 rate was higher in the PPI group than in the H2RA group (log-rank test, p = 0.009). Regression analyses showed that PPI exposure [adjusted hazard ratio 1.32, 95% confidence interval (CI) 1.11-1.58, p = 0.002] was associated with incident KDIGO-3 compared with H2RA use. This association remained consistent in sensitivity analyses. Additionally, the PPI group had a higher need for kidney replacement therapy compared with the H2RA group (3.6% vs. 2.1%, P = 0.012). CONCLUSIONS: Among septic patients at high risk for developing stress ulcers, PPI exposure was associated with incident KDIGO-3 AKI compared with H2RA use.