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BACKGROUND: DNA hypermethylation and hotspot mutations were frequently observed in the upstream and core promoter of telomerase reverse transcriptase (TERT), respectively, and they were associated with increased TERT expression and adverse clinical outcomes in thyroid cancer. In TERT promoter mutant cancer cells, the hypomethylated TERT mutant allele was active and the hypermethylated TERT wild-type allele was silenced. However, whether and how the upstream promoter methylation regulates TERT expression in TERT mutation-negative cells were largely unknown. METHODS: DNA demethylating agents 5-azacytidine and decitabine and a genomic locus-specific demethylation system based on dCas9-TET1 were used to assess the effects of TERT upstream promoter methylation on TERT expression, cell growth and apoptosis of thyroid cancer cells. Regulatory proteins binding to TERT promoter were identified by CRISPR affinity purification in situ of regulatory elements (CAPTURE) combined with mass spectrometry. The enrichments of selected regulatory proteins and histone modifications were evaluated by chromatin immunoprecipitation. RESULTS: The level of DNA methylation at TERT upstream promoter and expression of TERT were significantly decreased after treatment with 5-azacytidine or decitabine in TERT promoter wild-type thyroid cancer cells. Genomic locus-specific demethylation of TERT upstream promoter induced TERT downregulation, along with cell apoptosis and growth inhibition. Consistently, demethylating agents sharply inhibited the growth of thyroid cancer cells harboring hypermethylated TERT but had little effect on cells with TERT hypomethylation. Moreover, we identified that the chromatin remodeling protein CHD4 binds to methylated TERT upstream promoter and promotes its transcription by suppressing the enrichment of H3K9me3 and H3K27me3 at TERT promoter. CONCLUSIONS: This study uncovered the mechanism of promoter methylation mediated TERT activation in TERT promoter mutation-negative thyroid cancer cells and indicated TERT upstream promoter methylation as a therapeutic target for thyroid cancer.
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Background: Stigma is among the most prevalent and disturbing consequences of being infertile among women, yet it remains unknown whether fertility stigma is affected by irrational parenthood cognitions (IPC). The current study aimed to assess IPC, infertility stigma, and their interrelationship among a group of Chinese women referred to an infertility center in Changsha, Hunan, China. Methods: A cross-sectional study was conducted among 376 women seeking treatment for infertility in Changsha City, China. Pearson correlation test was used to explore the association between IPC and infertility stigma, while multivariate linear regression was used to explore the independent influencing factors of infertility stigma. Results: Participants had a mean score of 42.41 ± 13.03 for IPC and 62.89 ± 24.50 for ISS. IPC was highly correlated with infertility stigma with a large effect size (r = 0.55, p < 0.001). Multivariate linear regression showed that patients' infertility stigma was positively associated with IPC (ß = 1.06, p < 0.001) while negatively associated with education (ß = -5.4, p = 0.036) and disclosure of infertility (ß = -8.39, p = 0.001) (R 2 = 36 %). In addition, various influencing factors were identified for the four dimensions of infertility stigma. Conclusion: This study is the first to identify a positive association between irrational parenthood cognitions and infertility stigma among infertile women in China. Our findings provide useful guidance for the future development of effective anti-stigma intervention programs among infertile women.
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Pregnane X receptor (PXR) has been reported to regulate glycolipid metabolism. The dysfunction of intestinal barrier contributes to metabolic disorders. However, the role of intestinal PXR in metabolic diseases remains largely unknown. Here, we show that activation of PXR by tributyl citrate (TBC), an intestinal-selective PXR agonist, improves high fat diet (HFD)-induced obesity. The metabolic benefit of intestinal PXR activation is associated with upregulation of ß-1,3 galactosyltransferase 5 (B3galt5). Our results reveal that B3galt5 mainly expresses in the intestine and is a direct PXR transcriptional target. B3galt5 knockout exacerbates HFD-induced obesity, insulin resistance and inflammation. Mechanistically, B3galt5 is essential to maintain the integrity of intestinal mucus barrier. B3galt5 ablation impairs the O-glycosylation of mucin2, destabilizes the mucus layer, and increases intestinal permeability. Furthermore, B3galt5 deficiency abolishes the beneficial effect of intestinal PXR activation on metabolic disorders. Our results suggest the intestinal-selective PXR activation regulates B3galt5 expression and maintains metabolic homeostasis, making it a potential therapeutic strategy in obesity.
Subject(s)
Diet, High-Fat , Galactosyltransferases , Insulin Resistance , Intestinal Mucosa , Mice, Inbred C57BL , Mice, Knockout , Obesity , Pregnane X Receptor , Animals , Obesity/metabolism , Obesity/genetics , Pregnane X Receptor/metabolism , Pregnane X Receptor/genetics , Galactosyltransferases/metabolism , Galactosyltransferases/genetics , Mice , Diet, High-Fat/adverse effects , Intestinal Mucosa/metabolism , Male , Intestines , HumansABSTRACT
Rice husk is a locally available biomass for preparation of adsorbents to deal with cadmium (Cd) contamination in paddy system. In this study, phosphorylation of rice husk using H3PO4 and NH4H2PO4 was carried out in the presence of urea at 165â to obtain APB-C and NPB-C, respectively. According to the material characterizations, phosphonyl groups were successfully grafted on the rice husk. Both APB-C and NPB-C had high performance for Cd(II) adsorption with the capacities of 146 and 129 mg/g, respectively. The main mechanism of Cd(II) adsorption was ion exchange with NH4+. The adsorption capacity was linearly corelated with phosphorus content (R2 = 0.9997), while the Langmuir constant had high correlation efficient (R2 = 0.996) with phosphonyl group percentage. Further quantum chemical calculation showed higher interaction energy between Cd(II) and phosphonyl group than other groups. These results indicated that phosphonyl group governed Cd(II) adsorption on phosphorylated biomass.
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Heterocyclic amines (HAs) are a group of mutagenic and carcinogenic compounds produced from the processing of high-protein foods, which include 2-amino-3-methylimidazo[4, 5-f]quinoline (IQ) showing the strongest carcinogenic effect. Camels are able to digest HAs in foods, which provide rich microbial resources for the study. Thus, camel rumen and intestinal microbiota were used to degrade IQ, and the dominant microorganisms and their degradation characteristics were investigated. After three generations of culture with IQ as the sole carbon source, the highest abundance in rumen and intestinal microbes was found in the Proteobacteria phylum. The strains of third generation of the rumen contents were mainly attributed to the genera Brevundimonas and Pseudomonas, and the dominant genera in intestine were Ochrobactrum, Bacillus, and Pseudomonas. Microorganisms were further isolated and purified from the third generation cultures. These 27 strains from the rumen (L1-L27) and 23 strains from the intestine (C1-C23) were obtained. Among them, four strains with the most effective degrading abilities were as follows: L6 (28.55% of IQ degrading rate) and C1 (25.19%) belonged to the genus Ochrobactrum, L15 (23.41%) belonged to the genus Pseudomonas, and C16 (20.89%) were of the genus Bacillus. This study suggested the application of abundant microbial resources from camels' digestive tract to biodegrade foodborne toxins.
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Epimedium sagittatum (Sieb. et Zucc.) Maxim. (ESM) which accumulates several principal flavonoid compounds including epimedin A, B, C and icariin, is extensively utilized in traditional herbs for sexual dysfunction, osteoporosis etc. In China, ESM has a wealth of wild plant resources and characterized by significant variability in medicinal compounds accumulation. Understanding the diversity of ESMs can lead to better utilization of these plant resources. In this study, we integrated the metabolomic and transcriptomic analysis of three ESMs that originated in Anhui, Hubei and Jiangxi in China. Results showed that the flavonoid biosynthesis as well as the related gene expression in these ESMs revealed substantial differences. For example, the epimedin A, B, C and icariin as well as some related gene expression in ESMs from Anhui are significantly lower than those of in others. These results suggested that the ESMs from wild population without quality checkout may not be suitable for directly use as the materials for preparation of Chinese medicine and ESMs with different accumulation of metabolites could be used for distinct applications.
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Objective: Ferroptosis is implicated in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and vascular dementia, implying that it may have a regulatory effect on the progression of these diseases. However, the specific role of ferroptosis-related genes (FRGs) in Alzheimer's disease (AD) is not yet fully understood. The aim of the study was to detect ferroptosis related genes with regulatory functions in the disease and explore potential mechanisms in AD. Methods: Hub FRGs were obtained through multiple algorithms based on the GSE5281 dataset. The screening process was implemented by R packages including limma, WGCNA, glm and SVM-RFE. Gene Ontology classification and pathway enrichment analysis were performed based on FRGs. Biological processes involved with hub FRGs were investigated through GSVA and GSEA methods. Immune infiltration analysis was performed by the R package CIBERSORT. Receiver operating characteristic curve (ROC) was utilized to validate the accuracy of hub FRGs. The CeRNA network attempted to find non-coding RNA transcripts which may play a role in disease progression. Results: DDIT4, MUC1, KLHL24, CD44, and RB1 were identified as hub FRGs. As later revealed by enrichment analysis, the hub FRGs had important effects on AD through involvement in diverse AD pathogenesis-related pathways such as autophagy and glutathione metabolism. The immune microenvironment in AD shows increased numbers of resting NK cells, macrophages, and mast cells, with decreased levels of CD8 T cells when compared to healthy samples. Regulatory T cells were positively correlated with MUC1, KLHL24, and DDIT4 expression, while RB1 showed negative correlations with eosinophils and CD8 T cells, suggesting potential roles in modulating the immune environment in AD. Conclusion: Our research has identified five hub FRGs in AD. We concluded that ferroptosis may be involved in the disease.
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BACKGROUND: Hotspot mutations in the promoter of telomerase reverse transcriptase (TERT) gene are the most common genetic variants in hepatocellular carcinoma (HCC) and associated with poor prognosis of the disease. However, no drug was currently approved for treating TERT promoter mutation positive HCC patients. Here, we aim to explore the potential therapeutic strategy for targeting TERT promoter mutation in HCC. METHODS: The Liver Cancer Model Repository database was used for screening potential drugs to selectively suppress the growth of TERT promoter mutant HCC cells. RNA-seq, CRISPR-Cas9 technology and siRNA transfection were performed for mechanistic studies. Cell counting kit-8 (CCK8) assay and the xenograft tumour models were used for cell growth detection in vitro and in vivo, respectively. Cell apoptosis and cell cycle arrest were analysed by Annexin V-FITC staining and/or propidium iodide staining. RESULTS: PLK1 inhibitors were remarkably more sensitive to HCC cells harbouring TERT promoter mutation than wild-type cells in vitro and in vivo, which were diminished after TERT promoter mutation was edited to the wild-type nucleotide. Comparing the HCC cells with wild-type promoter of TERT, PLK1 inhibitors specifically downregulated Smad3 to regulate TERT for inducing apoptosis and G2/M arrest in TERT mutant HCC cells. Moreover, knockout of Smad3 counteracted the effects of PLK1 inhibitors in TERT mutant HCC cells. Finally, a cooperative effect of PLK1 and Smad3 inhibition was observed in TERT mutant cells. CONCLUSIONS: PLK1 inhibition selectively suppressed the growth of TERT mutant HCC cells through Smad3, thus contributed to discover a novel therapeutic strategy to treat HCC patients harbouring TERT promoter mutations. KEY POINTS: TERT promoter mutation confers sensitivity to PLK1 inhibitors in HCC. The selective growth inhibition of TERT mutant HCC cells induced by PLK1 inhibitor was mediated by Smad3. Combined inhibition of PLK1 and Smad3 showed a cooperative anti-tumor effect in TERT mutant HCC cells.
Subject(s)
Carcinoma, Hepatocellular , Cell Cycle Proteins , Liver Neoplasms , Polo-Like Kinase 1 , Promoter Regions, Genetic , Protein Serine-Threonine Kinases , Proto-Oncogene Proteins , Telomerase , Telomerase/genetics , Telomerase/antagonists & inhibitors , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/antagonists & inhibitors , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/antagonists & inhibitors , Cell Cycle Proteins/genetics , Cell Cycle Proteins/antagonists & inhibitors , Promoter Regions, Genetic/genetics , Promoter Regions, Genetic/drug effects , Animals , Mutation , Mice , Cell Line, Tumor , Apoptosis/drug effects , Apoptosis/geneticsABSTRACT
With the increased prevalence of nonalcoholic steatohepatitis (NASH) in the world, effective pharmacotherapy in clinical practice is still lacking. Previous studies have shown that dibenzazepine (DBZ), a Notch inhibitor, could alleviate NASH development in a mouse model. However, low bioavailability, poor water solubility, and extrahepatic side effects restrict its clinical application. To overcome these barriers, we developed a reactive oxygen species (ROS)-sensitive nanoparticle based on the conjugation of bilirubin to poly(ethylene glycol) (PEG) chains, taking into account the overaccumulation of hepatic ROS in the pathologic state of nonalcoholic steatohepatitis (NASH). The PEGylated bilirubin can self-assemble into nanoparticles in an aqueous solution and encapsulate insoluble DBZ into its hydrophobic cavity. DBZ nanoparticles (DBZ Nps) had good stability, rapidly released DBZ in response to H2O2, and effectively scavenged intracellular ROS of hepatocytes. After systemic administration, DBZ Nps could accumulate in the liver of the NASH mice, extend persistence in circulation, and improve the bioavailability of DBZ. Furthermore, DBZ Nps significantly improved glucose intolerance, relieved hepatic lipid accumulation and inflammation, and ameliorated NASH-induced liver fibrosis. Additionally, DBZ Nps had no significant extrahepatic side effects. Taken together, our results highlight the potential of the ROS-sensitive DBZ nanoparticle as a promising therapeutic strategy for NASH.
Subject(s)
Lipogenesis , Liver , Mice, Inbred C57BL , Nanoparticles , Non-alcoholic Fatty Liver Disease , Reactive Oxygen Species , Animals , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Reactive Oxygen Species/metabolism , Mice , Nanoparticles/chemistry , Lipogenesis/drug effects , Male , Liver/metabolism , Liver/drug effects , Liver/pathology , Receptors, Notch/metabolism , Receptors, Notch/antagonists & inhibitors , Humans , Inflammation/drug therapy , Inflammation/metabolism , Bilirubin , Polyethylene Glycols/chemistry , Disease Models, Animal , Hepatocytes/metabolism , Hepatocytes/drug effects , DibenzazepinesABSTRACT
This case report documents the first instance of Penicillin-Susceptible Methicillin-Resistant Staphylococcus aureus (PS-MRSA) in a Chinese psychiatric hospital. The strain was isolated from a patient with Alzheimer's disease who had a lower respiratory tract infection. Clinical and laboratory analyses, including mass spectrometry, antibiotic susceptibility testing, and whole-genome sequencing, confirmed the PS-MRSA strain. In this case, we systematically introduce the clinical symptoms, laboratory findings, and treatment responses associated with this PS-MRSA strain. This discovery offers a new perspective on our understanding of resistance mechanisms and expands our considerations for existing antibiotic treatments. It may fill a gap in the classification of MRSA strains, enhance the spectrum of MRSA resistance, and complete the therapeutic strategies for MRSA.
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Objective: The aim of this study was to identify genetic biomarkers and cellular communications associated with severe asthma in microarray data sets and single cell data sets. The potential gene expression levels were verified in a mouse model of asthma.Methods: We identified differentially expressed genes from the microarray datasets (GSE130499 and GSE63142) of severe asthma, and then constructed models to screen the most relevant biomarkers to severe asthma by machine learning algorithms (LASSO and SVM-RFE), with further validation of the results by GSE43696. Single-cell datasets (GSE193816 and GSE227744) were identified for potential biomarker-specific expression and intercellular communication. Finally, The expression levels of potential biomarkers were verified with a mouse model of asthma.Results: The 73 genes were differentially expressed between severe asthma and normal control. LASSO and SVM-RFE recognized three genes BCL3, DDIT4 and S100A14 as biomarkers of severe asthma and had good diagnostic effect. Among them, BCL3 transcript level was down-regulated in severe asthma, while S100A14 and DDIT4 transcript levels were up-regulated. The transcript levels of the three genes were confirmed in the mouse model. Infiltration of neutrophils and mast cells were found to be increased in severe asthma and may be associated with bronchial epithelial cells through BMP and NRG signalingConclusions: We identified three differentially expressed genes (BCL3, DDIT4 and S100A14) of diagnostic significance that may be involved in the development of severe asthma and these gene expressions could be serviced as biomarker of severe asthma and investigating the function roles could bring new insights into the underlying mechanisms.
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BACKGROUND: The dynamic and hierarchical nature of the functional brain network. The neural dynamical systems tend to converge to multiple attractors (stable fixed points or dynamical states) in long run. Little is known about how the changes in this brain dynamic "long-term" behavior of the connectivity flow of brain network in generalized anxiety disorder (GAD). METHODS: This study recruited 92 patients with GAD and 77 healthy controls (HC). We applied a reachable probability approach combining a Non-homogeneous Markov model with transition probability to quantify all possible connectivity flows and the hierarchical structure of brain functional systems at the dynamic level and the stationary probability vector (10-step transition probabilities) to describe the steady state of the system in the long run. A random forest algorithm was conducted to predict the severity of anxiety. RESULTS: The dynamic functional patterns in distributed brain networks had larger possibility to converge in bilateral thalamus, posterior cingulate cortex (PCC), right superior occipital gyrus (SOG) and smaller possibility to converge in bilateral superior temporal gyrus (STG) and right parahippocampal gyrus (PHG) in patients with GAD compared to HC. The abnormal transition probability pattern could predict anxiety severity in patients with GAD. LIMITATIONS: Small samples and subjects taking medications may have influenced our results. Future studies are expected to rule out the potential confounding effects. CONCLUSION: Our results have revealed abnormal dynamic neural communication and integration in emotion regulation in patients with GAD, which give new insights to understand the dynamics of brain function of patients with GAD.
Subject(s)
Brain , Magnetic Resonance Imaging , Humans , Brain/diagnostic imaging , Anxiety Disorders/psychology , Brain Mapping/methods , Temporal LobeABSTRACT
Ovarian cancer is the leading cause of gynecological cancer-related death. Drug resistance is the bottleneck in ovarian cancer treatment. The increasing use of novel drugs in clinical practice poses challenges for the treatment of drug-resistant ovarian cancer. Continuing to classify drug resistance according to drug type without understanding the underlying mechanisms is unsuitable for current clinical practice. We reviewed the literature regarding various drug resistance mechanisms in ovarian cancer and found that the main resistance mechanisms are as follows: abnormalities in transmembrane transport, alterations in DNA damage repair, dysregulation of cancer-associated signaling pathways, and epigenetic modifications. DNA methylation, histone modifications and noncoding RNA activity, three key classes of epigenetic modifications, constitute pivotal mechanisms of drug resistance. One drug can have multiple resistance mechanisms. Moreover, common chemotherapies and targeted drugs may have cross (overlapping) resistance mechanisms. MicroRNAs (miRNAs) can interfere with and thus regulate the abovementioned pathways. A subclass of miRNAs, "epi-miRNAs", can modulate epigenetic regulators to impact therapeutic responses. Thus, we also reviewed the regulatory influence of miRNAs on resistance mechanisms. Moreover, we summarized recent phase I/II clinical trials of novel drugs for ovarian cancer based on the abovementioned resistance mechanisms. A multitude of new therapies are under evaluation, and the preliminary results are encouraging. This review provides new insight into the classification of drug resistance mechanisms in ovarian cancer and may facilitate in the successful treatment of resistant ovarian cancer.
Subject(s)
MicroRNAs , Ovarian Neoplasms , Humans , Female , MicroRNAs/genetics , MicroRNAs/metabolism , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , DNA Methylation , Epigenesis, Genetic , Drug Resistance, Neoplasm/geneticsSubject(s)
Antineoplastic Agents , Ovarian Neoplasms , Female , Humans , Antineoplastic Agents/pharmacology , Ataxia Telangiectasia Mutated Proteins/antagonists & inhibitors , Cell Cycle Proteins/antagonists & inhibitors , Ovarian Neoplasms/drug therapy , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Protein-Tyrosine Kinases/antagonists & inhibitorsABSTRACT
Hydrogen (H2), produced by water electrolysis with the electricity from renewable sources, is an ideal energy carrier for achieving a carbon-neutral and sustainable society. Hydrogen evolution reaction (HER) is the cathodic half-reaction of water electrolysis, which requires active and robust electrocatalysts to reduce the energy consumption for H2 generation. Despite numerous electrocatalysts have been reported by the academia for HER, most of them were only tested under relatively small current densities for a short period, which cannot meet the requirements for industrial water electrolysis. To bridge the gap between academia and industry, it is crucial to develop highly active HER electrocatalysts which can operate at large current densities for a long time. In this review, the mechanisms of HER in acidic and alkaline electrolytes are firstly introduced. Then, design strategies towards high-performance large-current-density HER electrocatalysts from five aspects including number of active sites, intrinsic activity of each site, charge transfer, mass transfer, and stability are discussed via featured examples. Finally, our own insights about the challenges and future opportunities in this emerging field are presented.
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BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. In this study, we aimed to investigate the role and regulatory mechanism of Annexin A2 (ANXA2) in the pathogenesis of NAFLD. METHODS: Histological analyses and ELISA were used to illuminate the expression of ANXA2 in NAFLD and healthy subjects. The role of ANXA2 was evaluated using high-fat diet (HFD)-fed mice via vein injection of adeno-associated viruses (AAV) knocking down ANXA2 or non-targeting control (NC) shRNAs. Moreover, HepG2 and LO2 cells were employed as in vitro hepatocyte models to investigate the expression and function of ANXA2. RESULTS: ANXA2 was confirmed to be one of three hub genes in liver injury, and its expression was positively correlated with NAFLD activity score (NAS) and macrophage infiltration in NAFLD. Moreover, ANXA2 was significantly upregulated in NAFLD patients and HFD-fed mice. LPS/TLR4 pathway strongly upregulated ANXA2 expression, which is mediated by direct ANXA2 promoter binding by TLR4 downstream NF-κB p65 and c-Jun transcription factors. Increased ANXA2 expression was correlated with decreased autophagy flux and autophagy was activated by the depletion of ANXA2 in the models of NAFLD. Furthermore, ANXA2 interference led to the activation of AMPK/mTOR signaling axis, which may play a causal role in autophagy flux and the amelioration of steatosis. CONCLUSIONS: ANXA2 is a pathological predictor and promising therapeutic target for NAFLD. ANXA2 plays a crucial role in linking inflammation to hepatic metabolic disorder and injury, mainly through the blockage of AMPK/mTOR-mediated lipophagy.
Subject(s)
Annexin A2 , Autophagy , Non-alcoholic Fatty Liver Disease , TOR Serine-Threonine Kinases , Toll-Like Receptor 4 , Up-Regulation , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/pathology , Annexin A2/metabolism , Annexin A2/genetics , Animals , TOR Serine-Threonine Kinases/metabolism , Mice , Humans , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/genetics , Male , Signal Transduction , AMP-Activated Protein Kinases/metabolism , Lipid Metabolism , Hep G2 Cells , Mice, Inbred C57BL , Disease Models, Animal , Liver/pathology , Liver/metabolism , Diet, High-Fat/adverse effectsABSTRACT
Background: Acute gastroenteritis is a frequently encountered diarrheal illness in children, often self-limiting but occasionally linked to substantial mortality and morbidity, demanding effective approaches for assessment and intervention. While the utilization of the Pediatric Early Warning Score (PEWS) and the Situation-Background-Assessment-Recommendation system (SBAR) in pediatric patient management is recognized as effective, research in this area remains limited. Objective: Our study aimed to investigate the potential impact of PEWS and SBAR systems on the outcomes of pediatric patients with acute gastroenteritis. Methods: We conducted a randomized controlled trial at our hospital, enrolling 124 children aged 3 to 12 years diagnosed with acute gastroenteritis. These participants were randomly assigned to either a control group (62 cases) or an intervention group (62 cases). Different outcomes were assessed, including the frequency and duration of diarrhea and vomiting, the Modified Vesikari Scale (MVS), the Clinical Dehydration Scale (CDS), and follow-up physician visits. We utilized a two-group independent sample t test to compare outcomes between the two groups. Results: Our study resulted in statistically significant findings favoring the intervention group regarding the frequency and duration of diarrhea and vomiting, the MVS, the CDS, and the need for repeat healthcare visits. Conclusions: The integration of PEWS with SBAR appears to offer improved outcomes for children afflicted with acute gastroenteritis.
Subject(s)
Early Warning Score , Gastroenteritis , Child , Humans , Diarrhea/diagnosis , Diarrhea/therapy , Gastroenteritis/diagnosis , Gastroenteritis/therapy , Vomiting/therapy , Child, PreschoolABSTRACT
BACKGROUND: Cortical thickness reductions in major depressive disorder are distributed across multiple regions. Research has indicated that cortical atrophy is influenced by connectome architecture on a range of neurological and psychiatric diseases. However, whether connectome architecture contributes to changes in cortical thickness in the same manner as it does in depression is unclear. This study aims to explain the distribution of cortical thickness reductions across the cortex in depression by brain connectome architecture. METHODS: Here, we calculated a differential map of cortical thickness between 110 depression patients and 88 age-, gender-, and education level-matched healthy controls by using T1-weighted images and a structural network reconstructed through the diffusion tensor imaging of control group. We then used a neighborhood deformation model to explore how cortical thickness change in an area is influenced by areas structurally connected to it. RESULTS: We found that cortical thickness in the frontoparietal and default networks decreased in depression, regional cortical thickness changes were related to reductions in their neighbors and were mainly limited by the frontoparietal and default networks, and the epicenter was in the prefrontal lobe. CONCLUSION: Current findings suggest that connectome architecture contributes to the irregular topographic distribution of cortical thickness reductions in depression and cortical atrophy is restricted by and dependent on structural foundation.
Subject(s)
Depressive Disorder, Major , Humans , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/pathology , Diffusion Tensor Imaging , Brain/pathology , Prefrontal Cortex/diagnostic imaging , Atrophy/pathology , Magnetic Resonance ImagingABSTRACT
Repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (L-DLPFC) is commonly used for the clinical treatment of major depressive disorder (MDD). The neuroimaging biomarkers and mechanisms of rTMS are still not completely understood. This study aimed to explore the functional neuroimaging changes induced by rTMS in adolescents with MDD. A total of ten sessions of rTMS were administrated to the L-DLPFC in thirteen adolescents with MDD once a day for two weeks. All of them were scanned using resting-state functional magnetic resonance imaging at baseline and after rTMS treatment. The regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and the subgenual anterior cingulate cortex (sgACC)-based functional connectivity (FC) were computed as neuroimaging indicators. The correlation between changes in the sgACC-based FC and the improvement in depressive symptoms was also analyzed. After rTMS treatment, ReHo and ALFF were significantly increased in the L-DLPFC, the left medial prefrontal cortex, bilateral medial orbital frontal cortex, and the left ACC. ReHo and ALFF decreased mainly in the left middle occipital gyrus, the right middle cingulate cortex (MCC), bilateral calcarine, the left cuneus, and the left superior occipital gyrus. Furthermore, the FCs between the left sgACC and the L-DLPFC, the right IFGoper, the left MCC, the left precuneus, bilateral post-central gyrus, the left supplementary motor area, and the left superior marginal gyrus were enhanced after rTMS treatment. Moreover, the changes in the left sgACC-left MCC FC were associated with an improvement in depressive symptoms in early improvers. This study showed that rTMS treatment in adolescents with MDD causes changes in brain activities and sgACC-based FC, which may provide basic neural biomarkers for rTMS clinical trials.