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CT and MR are currently the most common imaging techniques for pancreatic cancer diagnosis. Accurate segmentation of the pancreas in CT and MR images can provide significant help in the diagnosis and treatment of pancreatic cancer. Traditional supervised segmentation methods require a large number of labeled CT and MR training data, which is usually time-consuming and laborious. Meanwhile, due to domain shift, traditional segmentation networks are difficult to be deployed on different imaging modality datasets. Cross-domain segmentation can utilize labeled source domain data to assist unlabeled target domains in solving the above problems. In this paper, a cross-domain pancreas segmentation algorithm is proposed based on Moment-Consistent Contrastive Cycle Generative Adversarial Networks (MC-CCycleGAN). MC-CCycleGAN is a style transfer network, in which the encoder of its generator is used to extract features from real images and style transfer images, constrain feature extraction through a contrastive loss, and fully extract structural features of input images during style transfer while eliminate redundant style features. The multi-order central moments of the pancreas are proposed to describe its anatomy in high dimensions and a contrastive loss is also proposed to constrain the moment consistency, so as to maintain consistency of the pancreatic structure and shape before and after style transfer. Multi-teacher knowledge distillation framework is proposed to transfer the knowledge from multiple teachers to a single student, so as to improve the robustness and performance of the student network. The experimental results have demonstrated the superiority of our framework over state-of-the-art domain adaptation methods.
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OBJECTIVE: To investigate differential associations of traditional and novel adiposity indices with visual impairment (VI) in the middle-aged and older Chinese population. METHODS AND ANALYSIS: Based on the China Health and Retirement Longitudinal Study, 7750 Chinese older adults aged over 45 were included at baseline 2011, and 4133 participants who accomplished all three interviews from 2011 to 2015 were adapted for longitudinal analyses. We enrolled six adiposity indices, including the body mass index (BMI), waist-to-height ratio (WHtR), weight-adjusted-waist index (WWI), a body shape index (ABSI), body roundness index (BRI) and conicity index (ConI). Visual status and other covariates included sociodemographic characteristics, medical supports and lifestyle-related factors. Cross-sectional correlations were assessed using univariate and multivariate logistic regression analyses. For longitudinal analysis, generalised linear models with generalised estimating equations were used to determine the association between time-varying adiposity and visual status. RESULTS: Higher levels of WHtR/WWI/ABSI/BRI/ConI were significantly associated with an increased prevalence of VI, whereas a higher BMI was associated with a decreased prevalence of VI. Only WWI was significantly related to the prevalence of VI after adjustment for multiple confounders in both cross-sectional and longitudinal analyses (all p values <0.05). The multivariable-adjusted OR (95% CI) of VI associated with the highest (vs lowest) quintile of WWI was 1.900 (1.407 to 2.565). CONCLUSION: WWI is a reliable alternative adiposity index that exhibits a dose-response association with the prevalence of VI in the Chinese population. The WWI-VI correlation may eliminate the obesity paradox in the ophthalmic epidemiological area and indicate the detrimental impact of changes in body composition on VI.
Subject(s)
Adiposity , Body Mass Index , Humans , Female , Male , Middle Aged , Aged , Cross-Sectional Studies , China/epidemiology , Prevalence , Vision Disorders/epidemiology , Vision Disorders/physiopathology , Risk Factors , Anthropometry , Longitudinal Studies , East Asian PeopleABSTRACT
Early studies have shown that the gut microbiota is a critical target during cadmium exposure. The prebiotic activity of epigallocatechin-3-gallate (EGCG) plays an essential role in treating intestinal inflammation and damage. However, the exact intestinal barrier protection mechanism of EGCG against cadmium exposure remains unclear. In this experiment, four-week-old mice were exposed to cadmium (5â¯mgâ¯kg-1) for four weeks. Through 16â¯S rDNA analysis, we found that cadmium disrupted the gut microbiota and inhibited the indole metabolism pathway of tryptophan (TRP), which serves as the principal microbial production route for endogenous ligands to activate the aryl hydrocarbon receptor (AhR). Additionally, cadmium downregulated the intestinal AhR signaling pathway and harmed the intestinal barrier function. Treatment with EGCG (20â¯mgâ¯kg-1) and the AhR agonist 6-Formylindolo[3,2-b] carbazole (FICZ) (1⯵g/d) significantly activated the AhR pathway and alleviated intestinal barrier injury. Notably, EGCG partially restored the gut microbiota and upregulated the TRP-indole metabolism pathway to increase the level of indole-related AhR agonists. Our findings demonstrate that cadmium dysregulates common gut microbiota to disrupt TRP metabolism, impairing the AhR signaling pathway and intestinal barrier. EGCG reduces cadmium-induced intestinal functional impairment by intervening in the intestinal microbiota to metabolize AhR agonists. This study offers insights into the toxic mechanisms of environmental cadmium and a potential mechanism to protect the intestinal barrier with EGCG.
Subject(s)
Cadmium , Catechin , Gastrointestinal Microbiome , Receptors, Aryl Hydrocarbon , Signal Transduction , Tryptophan , Animals , Catechin/analogs & derivatives , Catechin/pharmacology , Receptors, Aryl Hydrocarbon/metabolism , Gastrointestinal Microbiome/drug effects , Mice , Tryptophan/metabolism , Tryptophan/analogs & derivatives , Cadmium/toxicity , Signal Transduction/drug effects , Male , Intestines/drug effects , Intestines/pathology , Mice, Inbred C57BL , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Indoles/pharmacology , Carbazoles/pharmacologyABSTRACT
In this study, a green and efficient enrichment method for the four majors active diterpenoid components: pimelotide C, pimelotide A, simplexin, and 6α,7α-epoxy-5ß-hydroxy-12-deoxyphorbol-13-decanoate in the buds of Wikstroemia chamaedaphne was established using macroporous resin chromatography. The adsorption and desorption rates of seven macroporous resins were compared using static tests. The D101 macroporous resin exhibited the best performance. Static and dynamic adsorption tests were performed to determine the enrichment and purification of important bioactive diterpenoids in the buds of W. chamaedaphne. Diterpenoid extracts were obtained by using D101 macroporous resin from the crude extracts of W. chamaedaphne. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis demonstrated that most of the diterpenoids were enriched in diterpenoid extracts. These results confirmed that diterpenoids in the buds of W. chamaedaphne could be enriched using macroporous resin technology, and the enriched diterpenoid extracts showed more efficient activation of the latent human immunodeficiency virus. This study provides a novel strategy for discovering efficient and low-toxicity latency-reversing agents and a potential basis for the comprehensive development and clinical application of the buds of W. chamaedaphne.
Subject(s)
Diterpenes , Wikstroemia , Diterpenes/chemistry , Diterpenes/isolation & purification , Wikstroemia/chemistry , Humans , Tandem Mass Spectrometry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Chromatography, Liquid/methods , Porosity , Green Chemistry Technology , HIV-1/drug effects , Adsorption , HIV/drug effectsABSTRACT
A new compound, named coniferin B (1), and fourteen known compounds were purified and identified from the leaves and branches of Wikstroemia chamaedaphne Meisn. Their chemical structures were elucidated through analyzing spectroscopic and HRESIMS data. Compounds 2, 3, 5, 7-9, 11, and 13 were isolated from this plant for the first time. All compounds were assayed for cytotoxicity and activation of latent HIV activity on NH2 cells. The results showed that all compounds did not produce cytotoxicity at 10.0 µM and compounds 1, 9-11 showed weak activating activity with activation folds of 4.88, 7.14, 5.3, and 6.97, respectively.
Subject(s)
Plant Leaves , Wikstroemia , Plant Leaves/chemistry , Molecular Structure , Wikstroemia/chemistry , Humans , HIV-1/drug effects , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/isolation & purification , Anti-HIV Agents/pharmacology , Anti-HIV Agents/chemistry , Anti-HIV Agents/isolation & purification , Plant Stems/chemistryABSTRACT
The gut microbiome is crucial in maintaining fish health homeostasis. Disinfectants can kill important pathogens and disinfect fish eggs, yet their effect on the immune pathways and intestinal microbiome in healthy fish remains unknown. In this study, we investigated the effects of two disinfectants on the transcriptome profiles, immunological response, and gut microbiota dynamics of grass carp over a four-week trial. In particular, aquatic water was disinfected with 80 µg/L glutaraldehyde or 50 µg/L povidone-iodine. We found that glutaraldehyde and povidone-iodine induced gut antioxidant system and depressed the function of grass carp digestive enzymes. The results of the 16S rDNA high-throughput sequencing identified a reduction in the diversity of grass carp gut microbiota following the disinfectant treatment. Moreover, transcriptome profiling revealed that disinfectant exposure altered the immune-related pathways of grass carp and inhibited the expression of inflammation and tight junction related genes. Finally, the histopathological observation and apoptosis detection results suggested that the long-term diet of disinfectant destroyed intestinal structural integrity and promoted apoptosis. In conclusion, long-term exposure to disinfectants was observed to reduce oxidation resistance, suppress the immune response, dysbiosis of the intestinal flora, and resulted in increasing the apoptosis in intestinal of grass carp.
Subject(s)
Carps , Disinfectants , Gastrointestinal Microbiome , Water Pollutants, Chemical , Animals , Carps/immunology , Gastrointestinal Microbiome/drug effects , Disinfectants/toxicity , Water Pollutants, Chemical/toxicity , Intestines/drug effects , Intestines/immunology , Intestines/microbiology , Transcriptome/drug effectsABSTRACT
AIMS: Despite the success of single-cell RNA sequencing in identifying cellular heterogeneity in ischemic stroke, clarifying the mechanisms underlying these associations of differently expressed genes remains challenging. Several studies that integrate gene expression and gene expression quantitative trait loci (eQTLs) with genome wide-association study (GWAS) data to determine their causal role have been proposed. METHODS: Here, we combined Mendelian randomization (MR) framework and single cell (sc) RNA sequencing to study how differently expressed genes (DEGs) mediating the effect of gene expression on ischemic stroke. The hub gene was further validated in the in vitro model. RESULTS: We identified 2339 DEGs in 10 cell clusters. Among these DEGs, 58 genes were associated with the risk of ischemic stroke. After external validation with eQTL dataset, lactate dehydrogenase B (LDHB) is identified to be positively associated with ischemic stroke. The expression of LDHB has also been validated in sc RNA-seq with dominant expression in microglia and astrocytes, and melatonin is able to reduce the LDHB expression and activity in vitro ischemic models. CONCLUSION: Our study identifies LDHB as a novel biomarker for ischemic stroke via combining the sc RNA-seq and MR analysis.
Subject(s)
Ischemic Stroke , L-Lactate Dehydrogenase , Melatonin , Mendelian Randomization Analysis , Sequence Analysis, RNA , Animals , Humans , Genome-Wide Association Study/methods , Ischemic Stroke/genetics , Ischemic Stroke/metabolism , Isoenzymes/genetics , Isoenzymes/metabolism , L-Lactate Dehydrogenase/metabolism , L-Lactate Dehydrogenase/genetics , Mendelian Randomization Analysis/methods , Quantitative Trait Loci , Sequence Analysis, RNA/methods , Single-Cell Analysis/methods , MiceABSTRACT
OBJECTIVE: Optical Coherence Tomography (OCT) images can provide non-invasive visualization of fundus lesions; however, scanners from different OCT manufacturers largely vary from each other, which often leads to model deterioration to unseen OCT scanners due to domain shift. METHODS: To produce the T-styles of the potential target domain, an Orthogonal Style Space Reparameterization (OSSR) method is proposed to apply orthogonal constraints in the latent orthogonal style space to the sampled marginal styles. To leverage the high-level features of multi-source domains and potential T-styles in the graph semantic space, a Graph Adversarial Network (GAN) is constructed to align the generated samples with the source domain samples. To align features with the same label based on the semantic feature in the graph semantic space, Graph Semantic Alignment (GSA) is performed to focus on the shape and the morphological differences between the lesions and their surrounding regions. RESULTS: Comprehensive experiments have been performed on two OCT image datasets. Compared to state-of-the-art methods, the proposed method can achieve better segmentation. CONCLUSION: The proposed fundus lesion segmentation method can be trained with labeled OCT images from multiple manufacturers' scanners and be tested on an unseen manufacturer's scanner with better domain generalization. SIGNIFICANCE: The proposed method can be used in routine clinical occasions when an unseen manufacturer's OCT image is available for a patient.
Subject(s)
Algorithms , Image Interpretation, Computer-Assisted , Tomography, Optical Coherence , Tomography, Optical Coherence/methods , Humans , Image Interpretation, Computer-Assisted/methods , Fundus Oculi , Databases, Factual , Retinal Diseases/diagnostic imagingABSTRACT
To enhance the use of Cr2TiC2Tx MXene in spin electronics, it is essential to transform its spin-disordered state into a long-range ordered spin state. In this study, first-principles calculations show that Rh layers adhered to the Cr2TiC2Tx surfaces can transform its spin disordered state into a long-range spin order by donating electrons to the O terminations, resulting in Cr2TiC2Tx becoming a single-layer A-type antiferromagnet. As the proportion of F termination increases from 0 to 100%, the exchange coupling constant J1 of the compound escalates from 0.5 to 15.9 meV. Concurrently, the Néel temperature experiences a significant rise from 8 K to 110 K. The analysis of the density of states reveals that the obtained Cr2TiC2Tx exhibits excellent conductivity with O termination and semiconductor characteristics with F termination. These unique features make Cr2TiC2Tx a promising magnetic material for application in spin electronics.
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Early life stress (ELS) has been thought to increase vulnerability to developing psychiatric disorders later in life, while some researchers have found that adversity early in life may promote stress resilience. Studies investigating the resilient effect of maternal separation (MS) are still relatively few, and the underlying mechanisms remain unknown. In the current study, the effect of a single 24 h MS paradigm at postnatal day 9 (PND 9) in female C57BL/6J mice was investigated by assessing behavioral performance in middle adolescence. We demonstrated that, mice in MS group displayed decreased anxiety-like behavior and increased exploratory behavior than controls in the open field test and elevated plus maze test. Furthermore, MS mice exhibited improved hippocampal-dependent spatial learning in the Morris water maze test. This performance indicated behavioral resilience to early life stress. The protein expression levels of Homer1 isoforms, which are implicated in a variety of neuropsychiatric disorders, were evaluated using Western blot analysis. A significant increase in hippocampal Homer1a protein expression was observed immediately after MS, which subsequently decreased until adolescence (PND 27-42), when a significant increase was observed again. This distinctive change of hippocampal Homer1a protein expression pattern indicated that hippocampal Homer1a might play a role in behavioral resilience to MS in female C57BL/6J mice. In conclusion, this study demonstrated that exposure to a single 24 h MS at PND 9 promoted behavioral resilience of female C57BL/6J mice in middle adolescence. This behavioral resilience might be related to increased expression of hippocampal Homer1a.
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PURPOSE: To investigate the impacts of remimazolam tosilate on gastrointestinal hormones and motility in patients undergoing gastrointestinal endoscopy with sedation. METHODS: A total of 262 American Society of Anesthesiologists Physical Status I or II patients, aged 18-65 years, scheduled for gastrointestinal endoscopy with sedation, were randomly allocated into two groups (n = 131 each): the remimazolam tosilate group (Group R) and the propofol group (Group P). Patients in Group R received 0.2-0.25 mg/Kg remimazolam tosilate intravenously, while those in Group P received 1.5-2.0 mg/kg propofol intravenously. The gastrointestinal endoscopy was performed when the Modified Observer's Assessment of Alertness/Sedation scores were ≤3. The primary endpoints included the endoscopic intestinal peristalsis rating by the endoscopist; serum motilin and gastrin levels at fasting without gastrointestinal preparation (T0), before gastrointestinal endoscopy (T1), and before leaving the Post Anesthesia Care Unit (T2); and the incidences of abdominal distension during Post Anesthesia Care Unit. RESULTS: Compared with Group P, intestinal peristalsis rating was higher in Group R (P < .001); Group R showed increased motilin and gastrin levels at T2 compared with Group P (P < .01). There was a rise in motilin and gastrin levels at T1 and T2 compared with T0 and at T2 compared with T1 in both groups (P < .01). The incidence of abdominal distension was lower in Group R (P < .05). CONCLUSION: Compared with propofol used during gastrointestinal endoscopy with sedation, remimazolam tosilate mildly inhibits the serum motilin and gastrin levels, potentially facilitating the recovery of gastrointestinal motility.
Subject(s)
Benzodiazepines , Endoscopy, Gastrointestinal , Gastrointestinal Motility , Hypnotics and Sedatives , Propofol , Humans , Male , Female , Middle Aged , Adult , Gastrointestinal Motility/drug effects , Benzodiazepines/adverse effects , Propofol/administration & dosage , Propofol/pharmacology , Hypnotics and Sedatives/administration & dosage , Aged , Gastrins/blood , Motilin/blood , Conscious Sedation/methods , Adolescent , Gastrointestinal Hormones/bloodABSTRACT
OBJECTIVE: Multi-modal magnetic resonance (MR) image segmentation is an important task in disease diagnosis and treatment, but it is usually difficult to obtain multiple modalities for a single patient in clinical applications. To address these issues, a cross-modal consistency framework is proposed for a single-modal MR image segmentation. METHODS: To enable single-modal MR image segmentation in the inference stage, a weighted cross-entropy loss and a pixel-level feature consistency loss are proposed to train the target network with the guidance of the teacher network and the auxiliary network. To fuse dual-modal MR images in the training stage, the cross-modal consistency is measured according to Dice similarity entropy loss and Dice similarity contrastive loss, so as to maximize the prediction similarity of the teacher network and the auxiliary network. To reduce the difference in image contrast between different MR images for the same organs, a contrast alignment network is proposed to align input images with different contrasts to reference images with a good contrast. RESULTS: Comprehensive experiments have been performed on a publicly available prostate dataset and an in-house pancreas dataset to verify the effectiveness of the proposed method. Compared to state-of-the-art methods, the proposed method can achieve better segmentation. CONCLUSION: The proposed image segmentation method can fuse dual-modal MR images in the training stage and only need one-modal MR images in the inference stage. SIGNIFICANCE: The proposed method can be used in routine clinical occasions when only single-modal MR image with variable contrast is available for a patient.
Subject(s)
Algorithms , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Male , Image Processing, Computer-Assisted/methods , Prostate/diagnostic imaging , Image Interpretation, Computer-Assisted/methods , Prostatic Neoplasms/diagnostic imaging , Pancreas/diagnostic imagingABSTRACT
BACKGROUND: Deep learning based optical coherence tomography (OCT) segmentation methods have achieved excellent results, allowing quantitative analysis of large-scale data. However, OCT images are often acquired by different devices or under different imaging protocols, which leads to serious domain shift problem. This in turn results in performance degradation of segmentation models. PURPOSE: Aiming at the domain shift problem, we propose a two-stage adversarial learning based network (TSANet) that accomplishes unsupervised cross-domain OCT segmentation. METHODS: In the first stage, a Fourier transform based approach is adopted to reduce image style differences from the image level. Then, adversarial learning networks, including a segmenter and a discriminator, are designed to achieve inter-domain consistency in the segmentation output. In the second stage, pseudo labels of selected unlabeled target domain training data are used to fine-tune the segmenter, which further improves its generalization capability. The proposed method was tested on cross-domain datasets for choroid or retinoschisis segmentation tasks. For choroid segmentation, the model was trained on 400 images and validated on 100 images from the source domain, and then trained on 1320 unlabeled images and tested on 330 images from target domain I, and also trained on 400 unlabeled images and tested on 200 images from target domain II. For retinoschisis segmentation, the model was trained on 1284 images and validated on 312 images from the source domain, and then trained on 1024 unlabeled images and tested on 200 images from the target domain. RESULTS: The proposed method achieved significantly improved results over that without domain adaptation, with improvement of 8.34%, 55.82% and 3.53% in intersection over union (IoU) respectively for the three test sets. The performance is better than some state-of-the-art domain adaptation methods. CONCLUSIONS: The proposed TSANet, with image level adaptation, feature level adaptation and pseudo-label based fine-tuning, achieved excellent cross-domain generalization. This alleviates the burden of obtaining additional manual labels when adapting the deep learning model to new OCT data.
Subject(s)
Image Processing, Computer-Assisted , Retina , Tomography, Optical Coherence , Retina/diagnostic imaging , Image Processing, Computer-Assisted/methods , Humans , Unsupervised Machine Learning , Deep LearningABSTRACT
Microgravity is one of the most common causes counting for the bone loss. Mesenchymal stem cells (MSCs) contribute greatly to the differentiation and function of bone related cells. The development of novel MSCs biomarkers is critical for implementing effective therapies for microgravity induced bone loss. We aimed to find the new molecules involved in the differentiation and function of MSCs in mouse simulated microgravity model. We found CD226 was preferentially expressed on a subset of MSCs. Simulation of microgravity treatment significantly increased the proportion of CD226+ Lin- CD117- Sca1+ MSCs. The CD226+ MSCs produced higher IL-6, M-CSF, RANKL and lower CD200 expression, and promoted osteoclast differentiation. This study provides pivotal information to understand the role of CD226 in MSCs, and inspires new ideas for prevention of bone loss related diseases.
Subject(s)
Mesenchymal Stem Cells , Weightlessness , Animals , Mice , Weightlessness/adverse effects , Mesenchymal Stem Cells/metabolism , Cell Differentiation/physiology , Cells, Cultured , Weightlessness SimulationABSTRACT
Retinopathy of prematurity (ROP) usually occurs in premature or low birth weight infants and has been an important cause of childhood blindness worldwide. Diagnosis and treatment of ROP are mainly based on stage, zone and disease, where the zone is more important than the stage for serious ROP. However, due to the great subjectivity and difference of ophthalmologists in the diagnosis of ROP zoning, it is challenging to achieve accurate and objective ROP zoning diagnosis. To address it, we propose a new key area location (KAL) system to achieve automatic and objective ROP zoning based on its definition, which consists of a key point location network and an object detection network. Firstly, to achieve the balance between real-time and high-accuracy, a lightweight residual heatmap network (LRH-Net) is designed to achieve the location of the optic disc (OD) and macular center, which transforms the location problem into a pixel-level regression problem based on the heatmap regression method and maximum likelihood estimation theory. In addition, to meet the needs of clinical accuracy and real-time detection, we use the one-stage object detection framework Yolov3 to achieve ROP lesion location. Finally, the experimental results have demonstrated that the proposed KAL system has achieved better performance on key point location (6.13 and 17.03 pixels error for OD and macular center location) and ROP lesion location (93.05% for AP50), and the ROP zoning results based on it have good consistency with the results manually labeled by clinicians, which can support clinical decision-making and help ophthalmologists correctly interpret ROP zoning, reducing subjective differences of diagnosis and increasing the interpretability of zoning results.
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Objective.Neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) present many similar clinical features. However, there are significant differences in the progression of nAMD and PCV. and it is crucial to make accurate diagnosis for treatment. In this paper, we propose a structure-radiomic fusion network (DRFNet) to differentiate PCV and nAMD in optical coherence tomography (OCT) images.Approach.The subnetwork (RIMNet) is designed to automatically segment the lesion of nAMD and PCV. Another subnetwork (StrEncoder) is designed to extract deep structural features of the segmented lesion. The subnetwork (RadEncoder) is designed to extract radiomic features from the segmented lesions based on radiomics. 305 eyes (155 with nAMD and 150 with PCV) are included and manually annotated CNV region in this study. The proposed method was trained and evaluated by 4-fold cross validation using the collected data and was compared with the advanced differentiation methods.Main results.The proposed method achieved high classification performace of nAMD/PCV differentiation in OCT images, which was an improvement of 4.68 compared with other best method.Significance. The presented structure-radiomic fusion network (DRFNet) has great performance of diagnosing nAMD and PCV and high clinical value by using OCT instead of indocyanine green angiography.
Subject(s)
Choroid , Polypoidal Choroidal Vasculopathy , Humans , Choroid/blood supply , Tomography, Optical Coherence/methods , Radiomics , Fluorescein Angiography/methods , Retrospective StudiesABSTRACT
Since disinfectants are used all over the world to treat illnesses in people and other animals, they pose a major risk to human health. The comprehensive effects of disinfectant treatments on fish liver, especially the impacts on oxidative stress, toxicological effects, transcriptome profiles, and apoptosis, have not yet been fully analyzed. In the current investigation, healthy grass carp were exposed to 80 µg/L glutaraldehyde or 50 µg/L povidone-iodine for 30 days. First, the findings of enzyme activity tests demonstrated that the administration of glutaraldehyde could considerably increase oxidative stress by lowering T-SOD, CAT, and GPx and raising MDA. Furthermore, KEGG research revealed that exposure to glutaraldehyde and povidone-iodine stimulated the PPAR signal pathway. To further elucidate the transcriptome results, the relative expressions of related DEGs in the PPAR signal pathway were verified. Glutaraldehyde induced apoptosis in liver tissue of grass carp; however, it activated cytotoxicity and apoptosis in grass carp hepatocytes when exposed to glutaraldehyde or povidone-iodine. According to the current study, disinfectants can cause the impairment of the immune system, oxidative stress, and attenuation of the PPAR signal pathway in the liver of grass carp, making them detrimental as dietary supplements for grass carp, particularly in the aquaculture sector.
Subject(s)
Carps , Disinfectants , Animals , Humans , Povidone-Iodine/toxicity , Glutaral/toxicity , Peroxisome Proliferator-Activated Receptors , Liver , Hepatocytes , Disinfectants/toxicity , ApoptosisABSTRACT
Sepsis is a life-threatening syndrome leading to hemodynamic instability and potential organ dysfunction. Oridonin, commonly used in Traditional Chinese Medicine (TCM), exhibits significant anti-inflammation activity. To explore the protective mechanisms of oridonin against the pathophysiological changes, the authors conducted single-cell transcriptome (scRNA-seq) analysis on septic liver models induced by cecal ligation and puncture (CLP). They obtained a total of 63,486 cells, distributed across 11 major cell clusters, and concentrated their analysis on four specific clusters (hepatocytes/Heps, macrophages, endothelial/Endos and T/NK) based on their changes in proportion during sepsis and under oridonin treatment. Firstly, biological changes in Hep, which are related to metabolic dysregulation and pro-inflammatory signaling, are observed during sepsis. Secondly, they uncovered the dynamic profiles of macrophage's phenotype, indicating that a substantial number of macrophages exhibited a M1-skewed phenotype associated with pro-inflammatory characteristics in septic model. Thirdly, they detected an upregulation of both inflammatory cytokines and transcriptomic factor Nfkb1 expression within Endo, along with slight capillarization during sepsis. Moreover, excessive accumulation of cytotoxic NK led to an immune imbalance. Though, oridonin ameliorated inflammatory-related responses and improved the liver dysfunction in septic mice. This study provides fundamental evidence of the protective effects of oridonin against sepsis-induced cytokine storm.
Subject(s)
Cytokines , Diterpenes, Kaurane , Sepsis , Mice , Animals , Cytokines/genetics , Cytokines/pharmacology , Sepsis/complications , Sepsis/drug therapy , Sepsis/genetics , Liver , Gene Expression ProfilingABSTRACT
OBJECTIVE: To compare the short-term and long-term outcomes between robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. BACKGROUND: The clinical outcomes of RG over LG have not yet been effectively demonstrated. METHODS: This retrospective cohort study included 3599 patients with gastric cancer who underwent radical gastrectomy at eight high-volume hospitals in China from January 2015 to June 2019. Propensity score matching was performed between patients who received RG and LG. The primary end point was 3-year disease-free survival (DFS). RESULTS: After 1:1 propensity score matching, 1034 pairs of patients were enrolled in a balanced cohort for further analysis. The 3-year DFS in the RG and LG was 83.7% and 83.1% ( P =0.745), respectively, and the 3-year overall survival was 85.2% and 84.4%, respectively ( P =0.647). During 3 years of follow-up, 154 patients in the RG and LG groups relapsed (cumulative incidence of recurrence: 15.0% vs 15.0%, P =0.988). There was no significant difference in the recurrence sites between the 2 groups (all P >0.05). Sensitivity analysis showed that RG had comparable 3-year DFS (77.4% vs 76.7%, P =0.745) and overall survival (79.7% vs 78.4%, P =0.577) to LG in patients with advanced (pathologic T2-4a) disease, and the recurrence pattern within 3 years was also similar between the 2 groups (all P >0.05). RG had less intraoperative blood loss, lower conversion rate, and shorter hospital stays than LG (all P >0.05). CONCLUSIONS: For resectable gastric cancer, including advanced cases, RG is a safe approach with comparable 3-year oncological outcomes to LG when performed by experienced surgeons.
Subject(s)
Laparoscopy , Robotic Surgical Procedures , Stomach Neoplasms , Humans , Treatment Outcome , Retrospective Studies , Stomach Neoplasms/pathology , Gastrectomy , Propensity Score , Postoperative Complications/epidemiology , Postoperative Complications/surgeryABSTRACT
AIM: Pulmonary hypertension due to left heart disease (PH-LHD) is commonly seen in patients with heart failure (HF), but there are limited treatment options. Recent studies have shown an association between aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphisms and pulmonary hypertension (PH). Therefore, this study aimed to investigate the occurrence of ALDH2 rs671 polymorphisms, and the association between ALDH2 and risk of PH-LHD in patients with HF. It also investigated different ALDH2 genotypes and examined their association with cardiac structure and function in HF patients with PH-LHD. METHODS: A total of 178 HF patients were consecutively enrolled in this study: 102 without PH-LHD and 76 with PH-LHD. Clinical data, parameters of echocardiography, and relevant biochemical indexes were recorded in both groups. Differences in data obtained between groups were compared, and the risk of variant ALDH2 polymorphisms with PH-LHD in HF patients was analysed using univariate and multivariate logistic regression. RESULTS: The prevalence of ALDH2 rs671 GA/AA polymorphisms (variant ALDH2) was 24 of 102 patients (23.53%) in the HF without PH-LHD group, and 32 of 76 patients (42.10%) in the HF with PH-LHD group, with a statistically significant difference. Univariate and multivariate logistical regression showed that variant ALDH2 is an independent risk factor for HF combined with PH-LHD. A higher proportion of patients with variant ALDH2 in the HF with PH-LHD group had a tricuspid regurgitation velocity >2.8 m/s, and they had higher values of peak early diastolic velocity of the mitral orifice/peak velocity of the early diastolic wave of the mitral orifice, maximum frequency shift of pulmonary valve flow, and pulmonary artery stiffness. CONCLUSIONS: Variant ALDH2 may be an independent risk factor for HF combined with PH-LHD. Variant ALDH2 may also be involved in pulmonary artery remodelling and is a potential new target for clinical treatment of PH-LHD.