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BACKGROUND: There is increasing interest in utilizing AI-generated content for gadolinium-free contrast-enhanced breast MRI. PURPOSE: To develop a generative model for gadolinium-free contrast-enhanced breast MRI and evaluate the diagnostic utility of the generated scans. STUDY TYPE: Retrospective. POPULATION: Two hundred seventy-six women with 304 breast MRI examinations (49 ± 13 years, 243/61 for training/testing). FIELD STRENGTH/SEQUENCE: ZOOMit diffusion-weighted imaging (DWI), T1-weighted volumetric interpolated breath-hold examination (T1W VIBE), and axial T2 3D SPACE at 3.0 T. ASSESSMENT: A generative model was developed to generate contrast-enhanced scans using precontrast T1W VIBE and DWI images. The generated and real images were quantitatively compared using the structural similarity index (SSIM), mean absolute error (MAE), and Dice similarity coefficient. Three radiologists with 8, 5, and 5 years of experience independently rated the image quality and lesion visibility on AI-generated and real images within various subgroups using a five-point scale. Four breast radiologists, with 8, 8, 5, and 5 years of experience, independently and blindly interpreted four reading protocols: unenhanced MRI protocol alone and combined with AI-generated scans, abbreviated MRI protocol, and full-MRI protocol. STATISTICAL ANALYSIS: Results were assessed using t-tests and McNemar tests. Using pathology diagnosis as reference standard, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each reading protocol. A P value <0.05 was considered significant. RESULTS: In the test set, the generated images showed similarity to the real images (SSIM: 0.935 ± 0.047 [SD], MAE: 0.015 ± 0.012 [SD], and Dice coefficient: 0.726 ± 0.177 [SD]). No significant difference in lesion visibility was observed between real and AI-generated scans of the mass, non-mass, and benign lesion subgroups. Adding AI-generated scans to the unenhanced MRI protocol slightly improved breast cancer detection (sensitivity: 92.86% vs. 85.71%, NPV: 76.92% vs. 70.00%); achieved non-inferior diagnostic utility compared to the AB-MRI protocol and full-protocol (sensitivity: 92.86%, 95.24%; NPV: 75.00%, 81.82%). DATA CONCLUSION: AI-generated gadolinium-free contrast-enhanced breast MRI has potential to improve the sensitivity of unenhanced MRI in detecting breast cancer. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.
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Antibiotic resistance is one of the most concerned global health issues. However, comprehensive profiles of antibiotic resistance genes (ARGs) in various environmental settings are still needed to address modern antibiotic resistome. Here, Arctic soils and representative contaminated samples from ARG pollution sources were analyzed using metagenomic approaches. The diversity and abundance of ARGs in Arctic soils were significantly lower than those in contaminated samples (p < 0.01). ARG profiles in Arctic soils were featured with the dominance of vanF, ceoB, and bacA related to multidrug and bacitracin, whereas those from ARG pollution sources were characterized by prevalent resistance to anthropogenic antibiotics such as sulfonamides, tetracyclines, and beta-lactams. Mobile genetic elements (MGEs) were found in all samples, and their abundance and relatedness to ARGs were both lower in Arctic soils than in polluted samples. Significant relationships between bacterial communities and ARGs were observed (p < 0.01). Cultural bacteria in Arctic soils had clinically-concerned resistance to erythromycin, vancomycin, ampicillin, etc., but ARGs relevant to those antibiotics were undetectable in their genomes. Our results suggested that Arctic environment could be an important reservoir of novel ARGs, and antibiotic stresses could cause ARG pollution via horizontal gene transfer and enrichment of resistant bacteria.
Subject(s)
Anti-Bacterial Agents , Genes, Bacterial , Anti-Bacterial Agents/pharmacology , Soil , Bacteria/genetics , AmpicillinABSTRACT
Background: Breast cancer is the most common gynecological malignancy and the leading cause of cancer-related deaths in women. P-element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are novel non-coding RNAs whose abnormal expressions have been closely associated with multiple cancers. This study explored the roles and possible mechanisms of piRNA-31106 in breast cancer. Methods: The expression of piRNA-31106 in breast cancer tissues and cells was detected by reverse transcription polymerase chain reaction (RT-PCR). The pcDNA vector containing piRNA-31106 (pcDNA-piRNA-31106) and a short hairpin (sh)RNA containing piRNA-31106 (shRNA-piRNA-31106) were used to interfere with piRNA-31106 expression in breast cancer cells. The effects on cell proliferation, apoptosis/cell cycle, invasion, and metastasis were detected via Cell Counting Kit-8 (CCK-8), flow cytometry, transwell assays, and scratch tests, respectively. The protein expressions of murine double minute 2 (MDM2), cyclin-dependent kinase 4 (CDK4), and cyclinD1 were detected by Western blot analysis. The N6-methyladenosine (m6A) RNA methylation level and the binding relationship between piRNA-31106 and METTL3 were analyzed. The role of METTL3 in the regulation of breast cancer by piRNA-31106 was further analyzed by using small interfering (si)RNA targeting METTL3. Results: PiRNA-31106 was highly expressed in breast cancer tissues and cell lines MDA-MB-231 and MCF-7. Overexpression of piRNA-31106 promoted the viability, invasion, and migration of breast cancer, inhibited apoptosis, and promoted the expressions of MDM2, CDK4, and cyclinD1. Inhibition of piRNA-31106 showed the opposite effect. In addition, piRNA-31106 promoted the m6A methylation levels and facilitated methyltransferase-like 3 (METTL3) expression in MDA-MB-231 and MCF-7 cells. RNA immunoprecipitation (RIP) assays confirmed the binding relationship between piRNA-31106 and METTL3. Further experiments demonstrated that si-METTL3 could inhibit the regulatory effects of piRNA-31106 on breast cancer. Conclusions: PiRNA-31106 was significantly highly expressed in breast cancer and could promote breast cancer progression by regulating METTL3-mediated m6A RNA methylation.
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The atrial natriuretic peptide (ANP) and the brain natriuretic peptide (BNP) are critical biological makers and regulators of cardiac functions. Our previous results show that NPRA (natriuretic peptide receptor A)-deficient mice have distinct metabolic patterns and expression profiles compared with the control. Still, the molecular mechanism that could account for this observation remains to be elucidated. Here, methylation alterations were detected by mazF-digestion, and differentially expressed genes of transcriptomes were detected by a Genome Oligo Microarray using the myocardium from NPRA-deficient (NPRA-/-) mice and wild-type (NPRA+/+) mice as the control. Comprehensive analysis of m6A methylation data gave an altered landscape of m6A modification patterns and altered transcript profiles in cardiac-specific NPRA-deficient mice. The m6A "reader" igf2bp3 showed a clear trend of increase, suggesting a function in altered methylation and expression in cardiac-specific NPRA-deficient mice. Intriguingly, differentially m6A-methylated genes were enriched in the metabolic process and insulin resistance pathway, suggesting a regulatory role in cardiac metabolism of m6A modification regulated by NPRA. Notably, it was confirmed that the pyruvate dehydrogenase kinase 4 (Pdk4) gene upregulated the gene expression and the hypermethylation level simultaneously, which may be the key factor for the cardiac metabolic imbalance and insulin resistance caused by natriuretic peptide signal resistance. Taken together, cardiac metabolism might be regulated by natriuretic peptide signaling, with decreased m6A methylation and a decrease of Pdk4.
Subject(s)
Insulin Resistance , Mice , Animals , Guanylate Cyclase/genetics , Guanylate Cyclase/metabolism , Receptors, Atrial Natriuretic Factor/genetics , Receptors, Atrial Natriuretic Factor/metabolismABSTRACT
Obesity induced by a high-fat diet (HFD) is an important cause of impaired memory and cognitive function, but the underlying mechanisms are not clear. In the present study, we analyzed the levels of circRNAs in the hippocampus of C57BL/6J mice and evaluated the memory and cognition ability of C57BL/6J mice with HFD using Morris water maze and Y-maze approaches to explore the potential mechanisms linking circRNAs in obesity-associated cognitive impairment. Learning performance showed that HFD-induced obesity mice have impaired memory and cognition. The Arraystar analysis of the hippocampus displayed that HFD-induced obesity leads to the differential expression of circRNAs (DE-circRNAs) in mice. In total, 46 circular RNAs with elevated expression and 10 with decreased expression were identified. Among them, mmu_circRNA_004797 was identified to be significantly downregulated and the expression of mmu_circRNA_21040 was significantly upregulated in the HFD-fed mice, compared with control mice by PCR test. Bioinformatics analysis also showed that the upregulated circRNAs were related to the neuronal function and behavior, and material transport process, while downregulated circRNAs participated in the process of cell response to external stimuli, such as cellular response to nutrient levels. Furthermore, the KEGG pathway analysis showed that the upregulated circRNAs are mainly involved in Axon guidance, calcium signaling pathway, and ErbB signaling pathway. Only a single significant pathway, that is, "protein processing in endoplasmic reticulum", was observed in the downregulated circRNAs. Finally, we examined the deficits of hippocampal synaptic plasticity and detected the expression of ER stress-related protein. The results showed that ER stress was activated in the hippocampus, and hippocampal synaptic plasticity deficits were displayed. Our results demonstrated that circRNAs were most likely implicated in the predisposition to obesity-associated cognitive impairment.
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OBJECTIVE: To develop a deep learning model for synthesizing the first phases of dynamic (FP-Dyn) sequences to supplement the lack of information in unenhanced breast MRI examinations. METHODS: In total, 97 patients with breast MRI images were collected as the training set (n = 45), the validation set (n = 31), and the test set (n = 21), respectively. An enhance border lifelike synthesize (EDLS) model was developed in the training set and used to synthesize the FP-Dyn images from the T1WI images in the validation set. The peak signal-to-noise ratio (PSNR), structural similarity (SSIM), mean square error (MSE) and mean absolute error (MAE) of the synthesized images were measured. Moreover, three radiologists subjectively assessed image quality, respectively. The diagnostic value of the synthesized FP-Dyn sequences was further evaluated in the test set. RESULTS: The image synthesis performance in the EDLS model was superior to that in conventional models from the results of PSNR, SSIM, MSE, and MAE. Subjective results displayed a remarkable visual consistency between the synthesized and original FP-Dyn images. Moreover, by using a combination of synthesized FP-Dyn sequence and an unenhanced protocol, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRI were 100%, 72.73%, 76.92%, and 100%, respectively, which had a similar diagnostic value to full MRI protocols. CONCLUSIONS: The EDLS model could synthesize the realistic FP-Dyn sequence to supplement the lack of enhanced images. Compared with full MRI examinations, it thus provides a new approach for reducing examination time and cost, and avoids the use of contrast agents without influencing diagnostic accuracy.
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Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are important biological markers and cardiac function regulators. Natriuretic peptide receptor A (NPRA) binds to an ANP or BNP ligand and induces transmembrane signal transduction by elevating the intracellular cyclic guanosine monophosphate (cGMP) levels. However, the metabolic phenotype and related mechanisms induced by NPRA deletion remain ambiguous. Here, we constructed myocardial-specific NPRA deletion mice and detected the heart functional and morphological characteristics by histological analysis and explored the altered metabolic pattern and the expression patterns of proteins by liquid chromatography-mass spectrometry (LC-MS)-based omics technology. NPRA deficiency unexpectedly did not result in significant cardiac remodeling or dysfunction. However, compared with the matched littermates, NPRA-deficient mice had significant metabolic differences. Metabolomic analysis showed that the metabolite levels varied in cardiac tissues and plasma. In total, 33 metabolites were identified in cardiac tissues and 54 were identified in plasma. Compared with control mice, NPRA-deficient mice had 20 upregulated and six downregulated metabolites in cardiac tissues and 25 upregulated and 23 downregulated metabolites in plasma. Together, NPRA deficiency resulted in increased nucleotide biosynthesis and histidine metabolism only in heart tissues and decreased creatine metabolism only in plasma. Further proteomic analysis identified 136 differentially abundant proteins in cardiac tissues, including 54 proteins with higher abundance and 82 proteins with lower abundance. Among them, cytochrome c oxidase subunit 7c and 7b (Cox7c, Cox7b), ATP synthase, H+ transporting, mitochondrial Fo complex subunit F2 (ATP5J2), ubiquinol-cytochrome c reductase, complex III subunit X (Uqcr10), and myosin heavy chain 7 (Myh7) were mainly involved in related metabolic pathways. These results revealed the essential role of NPRA in metabolic profiles and may elucidate new underlying pathophysiological mechanisms of NPRA in cardiovascular diseases.
Subject(s)
Myocardium/metabolism , Receptors, Atrial Natriuretic Factor/deficiency , Animals , Metabolomics , Mice, Knockout , Phenotype , Protein Interaction Maps , Proteomics , RNA, Messenger/metabolism , Receptors, Atrial Natriuretic Factor/genetics , Receptors, Atrial Natriuretic Factor/metabolismABSTRACT
ABSTRACT: Endoscopic third ventriculostomy (ETV) is a safe and effective method for the management of obstructive hydrocephalus. Traditional approach is a transfrontal trajectory through the foramen of Monro to access and open the third ventricle floor. Though endoscopic endonasal transsphenoidal approach (EETA) for pituitary and skull base tumors has become increasingly popular, no published literature has explored its utility in performing an ETV. Here, the authors reported a successful ETV for obstructive hydrocephalus through the EETA. A 57-year-old male presenting with progressive headache and gait disturbance for 3âmonths was diagnosed with obstructive hydrocephalus. Brain MRI revealed an obstruction of cerebrospinal fluid (CSF) flow at the cerebral aqueduct and supratentorial hydrocephalus, accompanied with dilatation and downward herniation of the third ventricle floor. Considering the displacement of the third ventricle floor and the indication for surgery, an ETV was successfully performed through the EETA. No postoperative complication was observed. Both radiological and clinical evaluation postoperatively confirmed ETV success with decreased ventricular size, increased CSF flow across the floor of the third ventricle, and improved clinical signs. EETA is a feasible approach for ETV in selected cases of obstructive hydrocephalus. This approach provides a short trajectory to directly visualize and open the Liliequist's membrane and the displaced floor of the third ventricle, while minimizes damage to normal brain tissue. Skull base repair with nasoseptal flap ensures the success rate by preventing postoperative CSF leak and infection.
Subject(s)
Hydrocephalus , Neuroendoscopy , Third Ventricle , Cerebral Ventricles/surgery , Endoscopy , Humans , Hydrocephalus/surgery , Male , Middle Aged , Third Ventricle/diagnostic imaging , Third Ventricle/surgery , Treatment Outcome , VentriculostomyABSTRACT
Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are important biological markers and regulators of cardiac function. The natriuretic peptide receptor A (NPRA), also known as NPR1 or guanylyl cyclase A, binds ANP and BNP to initiate transmembrane signal transduction by elevating the intracellular levels of cyclic guanosine monophosphate. However, the effects and mechanisms downstream of NPRA are largely unknown. The aim of the present study was to evaluate the changes in the global pattern of mRNA and circular RNA (circRNA) expression in NPRA/ and NPRA+/+ myocardium. Differentially expressed mRNA molecules were characterised using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis and were found to be primarily related to metabolic processes. Moreover, circRNA expression was also examined, and a possible competing endogenous RNA network consisting of circRNA, microRNA (miRNA), and mRNA molecules was constructed. The results of this study indicated that NPRA may play a role in cardiac metabolism, which could be mediated by circRNA through endogenous competition mechanisms. These findings may provide insight into future characterisation of various ceRNA network pathways.
Subject(s)
Metabolism/genetics , Myocardium/metabolism , RNA, Circular/metabolism , RNA, Messenger/metabolism , Receptors, Atrial Natriuretic Factor/genetics , Animals , CRISPR-Cas Systems , Computational Biology , Gene Expression Profiling , Gene Ontology , Gene Regulatory Networks , Mice, Inbred C57BL , Mice, Knockout , MicroRNAs/metabolism , Oligonucleotide Array Sequence Analysis , SoftwareABSTRACT
Brain natriuretic peptide (BNP) is an important biological marker and regulator of cardiac function. BNP resistance is characterized by high concentrations of less functionally effective BNP and common in heart failure (HF) patients. However, the roles and consequences of BNP resistance remain poorly understood. Investigate the effects of cardiac BNP resistance and identify potential metabolic biomarkers for screening and diagnosis. Thirty patients and thirty healthy subjects were enrolled in this study. Cardiac functions were evaluated by echocardiography. The plasma levels of cyclic guanosine monophosphate (cGMP) and BNP were measured by enzyme-linked immunosorbent assay (ELISA) and the cGMP/BNP ratio is calculated to determine cardiac natriuretic peptide resistance. Liquid chromatograph tandem mass spectrometry (LC-MS) based untargeted metabolomics analysis was applied to screen metabolic changes. The cGMP/BNP ratio was markedly lower in HF patients than controls. The cGMP/BNP ratio and ejection fraction (EF) were strongly correlated (R 2 = 0.676, P < 0.05). Importantly, metabolic profiles were substantially different between HF patients and healthy controls. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that the differentially expressed metabolites are involved in signaling pathways that regulate cardiac functions. In HF patients, BNP resistance develops in association with a reduction in heart function and metabolic remodeling. It suggests possible functional roles of BNP resistance in the regulation of cardiac metabolism.
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Locally advanced breast cancer, which is defined as a malignant breast tumor that invades or adheres to the surrounding tissue, is characterized by the invasion of the chest wall and the skin surface by the tumor. Multiple lymph nodes are invaded and fuse into a mass, causing extensive axillary lymph node metastasis. However, locally advanced breast cancer does not exhibit distant metastasis. At present, in most hospitals in China and the rest of the world, this type of breast cancer is primarily managed through systematic and local treatments. However, a consensus concerning the optimal surgical method for chest wall reconstruction, which for many surgeons is a difficult and confusing procedure, has not been reached. In the past, many breast centers had used skin flap combined with hard mesh titanium alloy plate to repair the large chest wall defects. Although titanium alloy plate can maintain the stability of the chest wall, it may have a negative effect on the follow-up radiotherapy of breast cancer patients, which is a controversial method. In addition, titanium alloy mesh also has the risk of deformation and fracture. These factors will cause some hidden dangers to patient safety. According to the research, the soft mesh not only has the characteristics of satisfactory compatibility and robustness for maintaining the stability of chest wall, but also does not affect the postoperative radiotherapy of patients. Combined with the advantages of soft mesh, Our department treated a case of locally advanced breast cancer with chest wall invasion. Through cooperation between the breast surgery and thoracic surgery departments, a mesh repair plus transverse rectus abdominis myocutaneous (TRAM) combined with deep inferior epigastric perforator (DIEP) procedure was performed to remove the breast tumor and repair the large area of skin defect after surgery, and a relatively satisfactory therapeutic effect was achieved. In this case, we took two novel approaches: first, a 4-layer high-density polyethylene mesh was used to repair the defect; secondly, the inferior epigastric artery perforation was anastomosed with the thoracoacromial artery (end-to-end anastomosis) and the inferior epigastric vein perforation was anastomosed with the axillary vein (end-to-side anastomosis).
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BACKGROUND: The classification of benign versus malignant breast lesions on multi-sequence Magnetic Resonance Imaging (MRI) is a challenging task since breast lesions are heterogeneous and complex. Recently, deep learning methods have been used for breast lesion diagnosis with raw image input. However, without the guidance of domain knowledge, these data-driven methods cannot ensure that the features extracted from images are comprehensive for breast cancer diagnosis. Specifically, these features are difficult to relate to clinically relevant phenomena. PURPOSE: Inspired by the cognition process of radiologists, we propose a Knowledge-driven Feature Learning and Integration (KFLI) framework, to discriminate between benign and malignant breast lesions using Multi-sequences MRI. METHODS: Starting from sequence division based on characteristics, we use domain knowledge to guide the feature learning process so that the feature vectors of sub-sequence are constrained to lie in characteristic-related semantic space. Then, different deep networks are designed to extract various sub-sequence features. Furthermore, a weighting module is employed for the integration of the features extracted from different sub-sequence images adaptively. RESULTS: The KFLI is a domain knowledge and deep network ensemble, which can extract sufficient and effective features from each sub-sequence for a comprehensive diagnosis of breast cancer. Experiments on 100 MRI studies have demonstrated that the KFLI achieves sensitivity, specificity, and accuracy of 84.6%, 85.7% and 85.0%, respectively, which outperforms other state-of-the-art algorithms.
Subject(s)
Breast Neoplasms/diagnostic imaging , Deep Learning , Diagnosis, Computer-Assisted/methods , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging , Algorithms , Breast Neoplasms/pathology , Female , Humans , Image Processing, Computer-Assisted/methods , Models, Statistical , ROC CurveABSTRACT
The purpose of the present study was to explore agingassociated cardiac dysfunction and the possible mechanism by which swimming exercise modulates cardiac dysfunction in aged mice. Aged mice were divided into two groups: i) Aged mice; and ii) aged mice subjected to swimming exercises. Another cohort of 4monthold male mice served as the control group. Cardiac structure and function in mice were analyzed using hematoxylin and eosin staining, and echocardiography. The levels of oxidative stress were determined by measuring the levels of superoxide dismutase, malondialdehyde and reactive oxygen species (ROS). Levels of the endoplasmic reticulum (ER) stressrelated protein PKRlike ER kinase, glucoseregulated protein 78 and C/EBP homologous protein were determined to evaluate the level of ER stress. The aged group exhibited an abnormal cardiac structure and decreased cardiac function, both of which were ameliorated by swimming exercise. The hearts of the aged mice exhibited pronounced oxidative and ER stress, which were ameliorated by exercise, and was accompanied by the reactivation of myocardial cGMP and suppression of cGMPspecific phosphodiesterase type 5 (PDE5). The inhibition of PDE5 attenuated ageinduced cardiac dysfunction, blocked ROS production and suppressed ER stress. An ER stress inducer abolished the beneficial effects of the swimming exercise on cardiac function and increased ROS production. The present study suggested that exercise restored cardiac function in mice with ageinduced cardiac dysfunction by inhibiting oxidative stress and ER stress, and increasing cGMPprotein kinase G signaling.
Subject(s)
Aging/metabolism , Cyclic GMP-Dependent Protein Kinases/metabolism , Cyclic GMP/metabolism , Endoplasmic Reticulum Stress , Myocardium/pathology , Physical Conditioning, Animal , Swimming/physiology , Animals , Down-Regulation , Male , Mice, Inbred C57BL , Reactive Oxygen Species/metabolism , Signal TransductionABSTRACT
The occurrence and quantities of ARGs in extracellular and intracellular DNA (eARGs and iARGs) from sediments collected in two different types of aquaculture farms were investigated. A total of 20 ARG subtypes associated with 7 categories of commonly used antibiotics (e.g., aminoglycosides, beta-lactams, sulfonamides, tetracyclines) were identified, and some of these subtypes were not related to the antibiotics used. ARGs are mainly present in the iDNA form with the ratio of the total iARGs to eARGs being in the range of 7.9-45.5. The ratio of eARG to iARGs varies greatly with ARG subtypes, probably due to their differences in persistence as a part of eDNA. Significant correlation between int1 and ARGs was observed for both eDNA and iDNA in sediments from the aquaculture farms. Moreover, ARG pollution was more serious in bullfrog ponds than polyculture ponds due to the more frequent use of antibiotics in bullfrog rearing operations.
Subject(s)
Aquaculture/methods , DNA/genetics , Drug Resistance, Microbial/genetics , Ponds/chemistry , Animals , Anti-Bacterial Agents/pharmacology , Farms , Genes, Bacterial/drug effects , Geologic Sediments/chemistry , Rana catesbeiana , Tetracyclines , beta-LactamsABSTRACT
BACKGROUND: The incidence and radiological patterns of eosinophilic granuloma (EG) in China is not clear. We described the incidence, presentation, and imaging characteristics of Chinese EG patients in a tertiary hospital. METHODS: A retrospective chart review was performed from January 2004 to October 2017 at a single tertiary general hospital. Seventy-six patients were pathologically identified as EG. Besides, 60 patients with preoperative imaging diagnosis of "EG" were analyzed to reveal the radiological patterns and their diagnostic power. RESULTS: Fifty-three male and 23 female EG patients with a mean age of 18.1 ± 16.7 years (range 1-58 years) were retrospectively included. Significant differences were observed in gender (male to female = 2.3:1) and age (the highest incidence at the age of 0~5 years) for EG. EG predominantly involved the skeletal system: flat bones (31.43%) > irregular bones (24.76%) > long bones (22.86%) > other organs (20.95%). No obvious relationships between season, biochemical markers, and EG incidence were observed. The common presenting symptoms were pain followed with local mass, and most patients underwent surgical resection. Among 60 imagingly diagnosed "EG" patients from April 2009 to October 2017, only 22 were with histological confirmation. The correct diagnosis rates were 37.1% (13 out of 35), 16.7% (5 out of 30), and 22.2% (8 out of 36) for plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI), respectively. CONCLUSIONS: Chinese EG has a varied presentation, age distribution, and gender difference. EG diagnosis is still based on biopsy or histopathology instead of imaging techniques.
Subject(s)
Eosinophilic Granuloma/diagnostic imaging , Eosinophilic Granuloma/epidemiology , Magnetic Resonance Imaging , Tertiary Care Centers , Tomography, X-Ray Computed , Adolescent , Adult , Child , Child, Preschool , China/epidemiology , Cohort Studies , Female , Humans , Incidence , Infant , Magnetic Resonance Imaging/methods , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed/methods , Young AdultABSTRACT
Exogenously administered B-type natriuretic peptide (BNP) has been shown to provide cardioprotection against various heart diseases. However, the underlying mechanisms remain elusive. This study explores whether BNP exerts its cardioprotection against hypoxia/reoxygenation (H/R) injury under high glucose/high fat (HG/HF) conditions in cardiac H9c2 cells and uncovers the underlying mechanisms. Our data revealed that BNP significantly increased the cell viability and decreased the release of lactate dehydrogenase (LDH) and creatine kinase (CK), with a maximal effect at the BNP concentration of 10-7â¯mol/L. In addition, by analyzing the activation of cleaved caspase-3 and by Annexin V-FITC/PI staining, we showed that BNP attenuated H/R-induced cell apoptosis in HG/HF conditions. Western blot analysis showed enhanced phosphorylation of protein kinase RNA (PKR)-like endoplastmic reticulum (ER) kinase (PERK) and eukaryotic initiation factor 2α (eIF2α)(one of the three main signaling pathways in endoplastmic reticulum (ER) stress), and increased expression of GRP78 and CHOP proteins (ER stress-related proteins) in H9c2 cells which underwent H/R in HG/HF conditions. Treatment with BNP or 8-Br-cGMP (an analog of cGMP) reversed this activation. However, this effect was significantly weakened by KT-5823, a selective cGMP-dependent protein kinase G (PKG) inhibitor. In addition, similar to BNP, treatment with a specific inhibitor of ER stress tauroursodeoxycholic acid (TUDCA) protected the cells against H/R injury exposed to HG/HF conditions. In conclusion, these findings demonstrated that BNP effectively protected cells against H/R injury under HG/HF conditions by inhibiting the ER stress via activation of the cGMP-PKG signaling pathway.
Subject(s)
Endoplasmic Reticulum Stress/drug effects , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Natriuretic Peptide, Brain/pharmacology , Animals , Apoptosis/drug effects , Cell Line , Dietary Fats/adverse effects , Flow Cytometry , Glucose/adverse effects , Myocardial Reperfusion Injury/metabolism , Rats , Signal Transduction/drug effectsABSTRACT
OBJECTIVE: To evaluate the clinical outcome of intelligent inflated reduction combined with percutaneous pedicle screw fixation in treating thoracolumbar burst fractures. METHODS: The clinical data of 22 patients with thoracolumbar burst fractures of single segment treated from January 2013 to December 2015 were retrospectively analyzed. There were 12 males and 10 females, aged from 32 to 56 years old with an average of (42.4±8.6) years. Self-made intelligent pneumatic reset instrument was applied to 22 cases under anaesthesia reduction, and then percutaneous pedicle screw fixation was performed. Clinical features were observed and the clinical effects were evaluated by VAS, ODI, kyphotic angle (Cobb angle) and the injured vertebral anterior border height before and after operation. RESULTS: All the patients were followed up from 1 to 2.5 years with an average of 18 months. All fractures obtained bone healing, no complications such as loosening, displacement, breakage of pedicle screw and kyphosis were found. Preoperative, 1 week postoperative, and final follow-up, VAS scores of lumbar pain were 7.82±0.85, 3.09±0.92, 1.05±0.72;ODI scores were 84.2±11.2, 46.3±9.0, 12.2±4.3;Cobb angle were (16.3±5.4)°, (3.7±2.2)°, ( 5.5±2.6)°; the injured vertebral anterior border heights were (59.5±7.8)%, (86.9±6.0)%, (83.5±5.5)%, respectively. There was significant differences in VAS, ODI scores between any two times(P<0.05). At 1 week postoperative and final follow-up, Cobb angle, injuried vertebral anterior border height were obviously improved (P<0.05), and there was no significant difference between postoperative 1 week and final follow-up (P>0.05). CONCLUSIONS: It is safe and feasible surgical technique that intelligent inflated reduction combined with percutaneous pedicle screw fixation for thoracolumbar burst fractures. It has advantage of little trauma, reliable fixation, and less complication, etc. Therefore, it is a better choice for single-segment thoracolumbar burst fractures.
Subject(s)
Pedicle Screws , Spinal Fractures , Adult , Female , Fracture Fixation, Internal , Humans , Lumbar Vertebrae , Male , Middle Aged , Retrospective Studies , Thoracic VertebraeABSTRACT
Long non-coding RNAs recently were identified as key mediators of cancer metastasis. This study provided evidence that long non-coding RNA MALAT1 was up-regulated in breast cancer tissues and cell lines. MALAT1 promoted cancer cell invasion through inducing epithelial-mesenchymal transition. Interestingly, we revealed there was a reciprocal repression between MALAT1 and miR-204. ZEB2 was identified as a downstream target of miR-204 and MALAT1 exerted its function mainly through the miR-204/ZEB2 axis. Our findings suggested that MALAT1 may serve as a new diagnostic biomarker and therapy target for breast cancer.
Subject(s)
Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Homeodomain Proteins/genetics , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Repressor Proteins/genetics , Adult , Aged , Animals , Breast Neoplasms/pathology , Cell Line, Tumor , Epithelial-Mesenchymal Transition/genetics , Female , Humans , Mice , Middle Aged , Signal Transduction , Xenograft Model Antitumor Assays , Zinc Finger E-box Binding Homeobox 2ABSTRACT
INTRODUCTION: Infrasound is a mechanical vibration wave with frequency between 0.0001 and 20 Hz. It has been established that infrasound of 120 dB or stronger is dangerous to humans. However, the biological effects of low decibel infrasound are largely unknown. The purpose of this study was to investigate the effects of low decibel infrasound on the cardiac fibroblasts. MATERIALS AND METHODS: The cardiac fibroblasts were isolated and cultured from Sprague-Dawley rats. The cultured cells were assigned into the following four groups: control group, angiotensin II (Ang II) group, infrasound group, and Ang II+infrasound group. The cell proliferation and collagen synthesis rates were evaluated by means of [3H]-thymidine and [3H]-proline incorporation, respectively. The levels of TGF-ß were determined by enzyme-linked immunosorbent assay. Moreover, RNAi approaches were used for the analysis of the biological functions of miR-29a, and the phosphorylation status of Smad3 was detected using western blotting analysis. RESULTS: The results showed that low decibel infrasound significantly alleviated Ang II-induced enhancement of cell proliferation and collagen synthesis. DISCUSSION: Compared with the control, Ang II markedly decreased the expression of miR-29a levels and increased the secretion of TGF-ß and phosphorylation of Smad3, which was partly reversed by the treatment with low decibel infrasound. Importantly, knockdown of miR-29a diminished the effects of infrasound on the cardiac fibroblasts. In conclusion, low decibel infrasound inhibits Ang II-stimulated cardiac fibroblasts via miR-29a targeting TGF-ß/Smad3 signaling.
Subject(s)
Angiotensin II/pharmacology , Cell Proliferation/drug effects , Fibroblasts/drug effects , Myocardium/cytology , Vibration , Animals , Cells, Cultured , Collagen/drug effects , Collagen/metabolism , Enzyme-Linked Immunosorbent Assay , Fibroblasts/metabolism , MicroRNAs/drug effects , MicroRNAs/genetics , Phosphorylation/drug effects , Proline/drug effects , Proline/metabolism , RNA Interference , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Signal Transduction/drug effects , Smad3 Protein/drug effects , Smad3 Protein/metabolism , Thymidine/metabolism , Transforming Growth Factor beta/drug effects , Transforming Growth Factor beta/metabolism , TritiumABSTRACT
miR-133a has been demonstrated to play an important role in tumor progression. The aim of present study was to analyze the correlation between miR-133a expression level and clinicopathologic features and its prognostic significance in non-small cell lung cancer (NSCLC). The expression of miR-133a in 104 pairs of human lung cancer tissues and adjacent normal lung tissues were analyzed by qRT-PCR. Here we show that miR-133a was down-regulated in NSCLC. The levels of miR-133a were negatively correlated with the status of N classification (N0-N1 vs. N2-N3, P=0.000), clinical stage (I-II vs. III-IV, P=0.010) and MMP-14 expression (High vs. Low, P=0.012). The patients with low miR-133a expression had shorter survival time than those with high miR-133a expression. Multivariate analysis indicated that the level of miR-133a expression was an independent prognostic indicator (P=0.012) for the survival of patients with NSCLC. In conclusion, decreased expression of miR-133a might be a potential unfavorable prognostic factor for patients with NSCLC, and further studies would be needed to prove our findings.