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PURPOSE: We introduce a novel approach for bronchoscopic navigation that leverages neural radiance fields (NeRF) to passively locate the endoscope solely from bronchoscopic images. This approach aims to overcome the limitations and challenges of current bronchoscopic navigation tools that rely on external infrastructures or require active adjustment of the bronchoscope. METHODS: To address the challenges, we leverage NeRF for bronchoscopic navigation, enabling passive endoscope localization from bronchoscopic images. We develop a two-stage pipeline: offline training using preoperative data and online passive pose estimation during surgery. To enhance performance, we employ Anderson acceleration and incorporate semantic appearance transfer to deal with the sim-to-real gap between training and inference stages. RESULTS: We assessed the viability of our approach by conducting tests on virtual bronchscopic images and a physical phantom against the SLAM-based methods. The average rotation error in our virtual dataset is about 3.18 ∘ and the translation error is around 4.95 mm. On the physical phantom test, the average rotation and translation error are approximately 5.14 ∘ and 13.12 mm. CONCLUSION: Our NeRF-based bronchoscopic navigation method eliminates reliance on external infrastructures and active adjustments, offering promising advancements in bronchoscopic navigation. Experimental validation on simulation and real-world phantom models demonstrates its efficacy in addressing challenges like low texture and challenging lighting conditions.
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BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung interstitial lesions with the disease pathophysiology incompletely understood, which is a serious and fatal disorder with limited treatment options. Mesenchymal stem cells (MSCs) have exhibited promising therapeutic capability for IPF. While most types of MSCs are obtained invasively, urine-derived stem cells (USCs) can be gained in a safe, noninvasive, and inexpensive procedure, which are readily available and reported to exhibit no risk of teratoma formation or oncogenic potential in vivo, sounding alternative to other MSCs. This study aims to investigate the therapeutic effect and mechanism of USCs on IPF, using a bleomycin (BLM)-induced IPF model in mice. METHODS: Cell surface marker examination by flow cytometry analysis and cell differentiation culture were used to characterize USCs obtained from healthy individuals. BLM was instilled endotracheally in adult C57BL/6 mice, followed by USCs or human bone marrow-derived mesenchymal stem cells (BMSCs) treatment by tail vein injection on day 14. Mice were euthanized on day 14 before administration or day 21 for the evaluation of pulmonary histopathology and hydroxyproline (HYP) content. Inflammatory factors of the lung, including transforming growth factor (TGF)-ß1, TNF-α, IL-6, MMP2 were analyzed by quantitative real-time PCR (qRT-PCR). Additionally, immunohistochemistry (IHC) and western blotting (WB) were applied to evaluate the expression of α-SMA and activation of TGF-ß1-Smad2/3 in lung. RESULTS: USCs highly expressed CD29 and CD90, showing negative expression of hematopoietic stem cell markers (CD45, CD34) and could differentiate into, at least, bone and fat in vitro. In mice challenged with BLM, septal thickening and prominent fibrosis were observed on day 14, with higher HYP content and mRNA levels of TGF-ß1, TNF-α and IL-6 exhibited, compared to untreated mice. USCs could migrate to lung and accumulate there in mouse model after intravenous injection. Transplantation of USCs into BLM-induced mice improved their pulmonary histopathology, decreasing Ashcroft score, Szapiel score, HYP content and mRNA levels of TGF-ß1 and MMP2 of lung, similar to the effects of BMSCs. IHC and WB further revealed that USCs could inhibit activation of the TGFß1-Smad2/3 pathway of lung in vivo. CONCLUSIONS: Transplantation of USCs effectively reverses pulmonary fibrotic phenotype in an experimental IPF model, inhibiting the TGF-ß1-Smad2/3 pathway, a key driver of fibrosis. These results suggest the therapeutic application of USCs for IPF, instead of other types of MSCs obtained invasively.
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Background: Squamous cell carcinoma of the lung (LUSC) is a severe and highly lethal malignant tumor of the respiratory system, and its molecular mechanisms at the molecular level remain unc\lear. Methods: We acquired RNA-seq data from 8 surgical samples obtained from early-stage LUSC and adjacent non-cancerous tissues from 3 different centers. Utilizing Deseq2, we identified 1088 differentially expressed genes with |LogFC| > 1 and a p-value < 0.05 threshold. Furthermore, through MR analysis of Exposure Data for 26,153 Genes and 63,053 LUSC Patients, incorporating 7,838,805 SNPs as endpoints, we identified 213 genes as potential exposure factors. Results: After intersecting the results, we identified 5 differentially expressed genes, including GYPE, PODXL2, RNF182, SIRPG, and WNT7A. PODXL2 (OR 95% CI, 1.169 (1.040 to 1.313)) was identified as an exposed risk factor, with p-values less than 0.01 under the inverse variance weighted model. GO and KEGG analyses revealed enhanced ubiquitin-protein transferase activity and activation of pathways such as the mTOR signaling pathway and Wnt signaling pathway. Immune infiltration analysis showed downregulation of Plasma cells, T cells regulatory (Tregs), and Dendritic cells activated by the identified gene set, while an enhancement was observed in Macrophages M1. Furthermore, we externally validated the expression levels of these five genes using RNA-seq data from TCGA database and 11 GEO datasets of LUSC, and the results showed SIRPG could induce LUSC. Conclusion: SIRPG emerged as a noteworthy exposure risk factor for LUSC. Immune infiltration analysis highlighted Macrophages M1 and mTOR signaling pathway play an important role in LUSC.
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BACKGROUND: To observe the occurrence of related complications after self-expandable metallic (SEM) airway stents implantation with different diameters at different time points, and to provide theoretical basis for the optimal chioce of existing airway stents in clinical practice. METHODS: Healthy New Zealand white rabbits were used to establish benign tracheal stenosis models after chest CT examination. Forty-fivemodel rabbits with more than 50% of airway stenosis were divided into two groups. Small-diameter SEM stents (The ratio of stent diameter to airway diameter is nearly 1.0) were implanted in Group A in 21 rabbits, and large-diameter tracheal stents (The ratio of stent diameter to airway diameter is more than 1.2) were implanted in Group B in 24 rabbits. Stent-related complications were observed after stent implantation in 2nd,4th,8th, and 12th week by bronchoscopygross anatomy, pathological and the expressions of IL-1RA, IL-8 and MMP9 in involved tracheal. RESULTS: The incidence rate of tracheomalacia of stent was significantly higher in group B (24/24 100%) than that in group A (1 /21,4.8%) (P < 0.05). The incidence rate of scar contracture at both ends of stent was significantly higher than in group B (11 / 24,45.8%) that in group A (2 /21, 9.5%) (P < 0.05). The pathological results of both A and B showed that the columnar epithelium of bronchial mucosa began to damage and detach, inflammatory cells infiltrated after 2nd and 4th week of stenting, The epithelium was repaired, the lamina propria glands almost disappeared, collagen fiber proliferation was obvious, and scars were formed after 8th and 12th week of stenting. ELISA results revealed that the expressions of IL-1RA, IL-8, and MMP9 were increased in the stent group than in model rabbit with benign tracheal stenosis. IL-1RA and MMP9 increased at different periods in group B, but the expression of IL-1RA and MMP9 showed a tread of increasing in the early stage and then decreasing in group A. CONCLUSION: Metal stents can cause different degrees of stent-related complications in rabbits with benign tracheal stenosis. The incidence of stent-induced tracheomalacia and scar contracture were higher in Group B than that in Group A. IL-1RA, IL-8 and MMP9 may be involved in the development of complications after stentimplantation and peak value of group B movered backward. ing.
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Contratura , Estenose Traqueal , Traqueomalácia , Coelhos , Animais , Proteína Antagonista do Receptor de Interleucina 1 , Metaloproteinase 9 da Matriz , Estenose Traqueal/etiologia , Estenose Traqueal/cirurgia , Cicatriz , Interleucina-8 , Stents/efeitos adversosRESUMO
Dysfunctional mutations in SAMHD1 cause Aicardi-Goutières Syndrome, an autoinflammatory encephalopathy with elevated interferon-α levels in the cerebrospinal fluid. Whether loss of function mutations in SAMHD1 trigger the expression of other cytokines apart from type I interferons in Aicardi-Goutières Syndrome is largely unclear. This study aimed to explore whether SAMHD1 dysfunction regulated the expression of IL-34, a key cytokine controlling the development and maintenance of microglia, in SH-SY5Y neural cells. We found that downregulation of SAMHD1 in SH-SY5Y cells resulted in the upregulation of IL-34 expression. The protein and mRNA levels of NF-κB p65, the transactivating subunit of a transcription factor NF-κB, were also upregulated in SAMHD1-knockdown SH-SY5Y cells. It was further found SAMHD1 knockdown in SH-SY5Y cells induced an upregulation of IL-34 expression through the canonical NF-κB-dependent pathway in which NF-κB p65, IKKα/ß and the NF-κB inhibitor IκBα were phosphorylated. Moreover, knockdown of SAMHD1 in SH-SY5Y cells led to the translocation of NF-κB p65 into the nucleus and promoted NF-κB transcriptional activity. In conclusion, we found SAMHD1 dysfunction induced IL-34 expression via NF-κB p65 in neuronal SH-SY5Y cells. This finding could lay the foundation for exploring the role of IL-34-targeting microglia in the pathogenesis of Aicardi-Goutières Syndrome.
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Doenças Autoimunes do Sistema Nervoso , Malformações do Sistema Nervoso , Neuroblastoma , Humanos , NF-kappa B/metabolismo , Proteína 1 com Domínio SAM e Domínio HD , Neuroblastoma/genética , Inibidor de NF-kappaB alfa , Citocinas , InterleucinasRESUMO
Lung cancer is the leading cause of cancer-related death, with high morbidity and mortality rates due to the lack of reliable methods for diagnosing lung cancer at an early stage. Low-dose computed tomography can help detect abnormal areas in the lungs, but only 16% of cases are diagnosed early. Tests for lung cancer markers are often employed to determine genetic expression or mutations in lung carcinogenesis. Serum glycome analysis is a promising new method for early lung cancer diagnosis as glycopatterns exhibit significant differences in lung cancer patients. In this study, we employed a solid-phase chemoenzymatic method to systematically compare glycopatterns in benign cases, adenocarcinoma before and after surgery, and advanced stages of adenocarcinoma. Our findings indicate that serum high-mannose levels are elevated in both benign cases and adenocarcinoma, while complex N-glycans, including fucose and 2,6-linked sialic acid, are downregulated in the serum. Subsequently, we developed an algorithm that utilizes 16 altered N-glycans, 7 upregulated and 9 downregulated, to generate a score based on their intensity. This score can predict the stages of cancer progression in patients through glycan characterization. This methodology offers a potential means of diagnosing lung cancer through serum glycome analysis.
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Adenocarcinoma , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Polissacarídeos/metabolismo , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , FucoseRESUMO
BACKGROUND: Developmental delay (DD) occurs when children fail to reach developmental milestones in comparison to peers of the same age range. However, there are no valuable biomarkers for the early diagnosis of DD. Since there is no specific marker for screening the disease, we evaluated plasma NSE, TNF-α and sIL2-Rα as potential markers for this purpose. METHODS: In this cross-sectional randomized case-control study, a total of 174 DD patients and 49 matched elderly controls aged between 2 months and 60 months were recruited. A sensitive enzyme-linked immunosorbent assay and an immunoradiometric assay were used to evaluate the levels of plasma IL-1, IL-6, IL-8, IL-10, sIL2-Rα, TNF-α, and NSE. Statistical analyses using t test, χ2, ANOVA, ROC curves and binary logistic regression models were performed. RESULTS: In comparison to the control group, the DD group had greater levels of NSE, TNF-α, and sIL2-Rα(p < 0.05). In the binary logistic regression analysis of DD, NSE had an odds ratio (OR) of 1.783 (95 % CI 1.297 to 2.451, p = 0.000), indicating that NSE was an independent risk factor for DD. The plasma TNF-α level was positively correlated with plasma NSE and sIL2-Rα levels in the DD group (r = 0.366 and 0.433, respectively), and the DQ score and plasma sIL2-Rα level in the DD group were positively correlated. The ROC curve revealed that the respective areas under the NSE, TNF-α, and sIL2-Rα ROC curves were 0.9797, 0.9365, and 0.8533, respectively. Moreover, a significant increase in AUC was observed using combined ROC curve analysis. CONCLUSIONS: Children with DD have significantly altered plasma concentrations of sIL2-Rα, NSE, and TNF-α. NSE, TNF-α and sIL2-Rα can be used as DD blood biomarkers. This information may be helpful in early diagnosis and intervention.
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Fosfopiruvato Hidratase , Fator de Necrose Tumoral alfa , Idoso , Criança , Humanos , Lactente , Curva ROC , Estudos de Casos e Controles , Estudos Transversais , Subunidade alfa de Receptor de Interleucina-2 , BiomarcadoresRESUMO
BACKGROUND: This study assessed the quality distribution of non-mydriatic fundus photographs (NMFPs) in real-world glaucoma screening and analysed its influencing factors. METHODS: This cross-sectional study was conducted in primary healthcare centres in the Yinzhou District, China, from 17 March to 3 December 2021. The quality distribution of bilateral NMFPs was assessed by the Digital Reading Department of the Eye Hospital of Wenzhou Medical University. Generalised estimating equations and logistic regression models identified factors affecting image quality. RESULTS: A total of 17 232 photographs of 8616 subjects were assessed. Of these, 11.9% of images were reliable for the right eyes, while only 4.6% were reliable for the left eyes; 93.6% of images were readable in the right eyes, while 90.3% were readable in the left eyes. In adjusted models, older age was associated with decreased odds of image readability (adjusted OR (aOR)=1.07, 95% CI 1.06~1.08, p<0.001). A larger absolute value of spherical equivalent significantly decreased the odds of image readability (all p<0.001). Media opacity and worse visual acuity had a significantly lower likelihood of achieving readable NMFPs (aOR=1.52, 95% CI 1.31~1.75; aOR=1.70, 95% CI 1.42~2.02, respectively, all p<0.001). Astigmatism axes within 31°~60° and 121°~150° had lower odds of image readability (aOR=1.35, 95% CI 1.11~1.63, p<0.01) than astigmatism axes within 180°±30°. CONCLUSIONS: The image readability of NMFPs in large-scale glaucoma screening for individuals 50 years and older is comparable with relevant studies, but image reliability is unsatisfactory. Addressing the associated factors may be vital when implementing ophthalmological telemedicine in underserviced areas. TRIAL REGISTRATION NUMBER: ChiCTR2200059277.
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Astigmatismo , Retinopatia Diabética , Glaucoma , Humanos , Midriáticos , Estudos Transversais , Reprodutibilidade dos Testes , Retinopatia Diabética/diagnóstico , Glaucoma/diagnóstico , Atenção Primária à SaúdeRESUMO
In this work, we aim to evaluate the association of the genetically proxied effect of metformin on blood pressure (BP) and hypertension through a drug target-based Mendelian randomization (MR) analysis. Thirty-two instrumental variables for five metformin targets (i.e., AMP-activated protein kinase (AMPK), growth differentiation factor 15 (GDF15), mitochondrial glycerol 3 (MG3), mitochondrial complex I (MCI), and glucagon (GCG)) were introduced to the MR analysis on the datasets of hypertension, systolic and diastolic blood pressure (SBP and DBP). The MR analyses demonstrated that the MCI- and MG3-specific metformin's use would significantly reduce SBP, DBP, and hypertension risk. The meta-analyses showed that the genetically proxied metformin's use equivalent to a 6.75 mmol/mol reduction on HbA1c could decrease both the SBP (beta = - 1.05, P < 0.001) and DBP (beta = - 0.51, P = 0.096). Furthermore, metformin's use was also implied to reduce the hypertension risk. The MG3- and MCI-dependent metformin's effect may play key roles in the anti-hypertension function.
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Ribonuclease (RNA) modifications can alter cellular function and lead to differential immune responses by acting as discriminators between RNAs from different phyla. RNA glycosylation has recently been observed at the cell surface, and its dysregulation in disease may change RNA functions. However, determining which RNA substrates can be glycosylated remains to be explored. Here, we develop a solid-phase chemoenzymatic method (SPCgRNA) for targeting glycosylated RNAs, by which glycosylated RNA substrates can be specifically recognized. We found the differential N-glycosylation of small RNAs in hTERT-HPNE and MIA PaCa-2 cancer cells using SPCgRNA. RNA-Seq showed that the changes in glyco-miRNAs prepared from SPCgRNA were consistent with those of traditional methods. The KEGG signaling pathway analysis revealed that differential miRNA glycosylation can affect tumor cell proliferation and survival. Further studies found that NGI-1 significantly inhibited the proliferation, migration, and circulation of MIA PaCa-2 and promoted cell apoptosis. In addition, ß-1,4-galactosyltransferase 1 (B4GALT1) not only affected the expression level of glycosylated miRNAs hsa-miR-21-5p but also promoted cell apoptosis and inhibited the cell cycle possibly through the p53 signaling pathway, while B4GALT1 and p53 were also affected following the hsa-miR-21-5p increase. These results suggest that B4GALT1 may catalyze miRNAs glycosylation, which further promotes cancer cell progression.
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RNA , Glicosilação , RNA/química , RNA/metabolismo , Oxirredução , Perfilação da Expressão Gênica , Humanos , Linhagem Celular Tumoral , Transdução de SinaisRESUMO
BACKGROUND: Hydrogen/oxygen therapy contribute to ameliorate dyspnea and disease progression in patients with respiratory diseases. Therefore, we hypothesized that hydrogen/oxygen therapy for ordinary coronavirus disease 2019 (COVID-19) patients might reduce the length of hospitalization and increase hospital discharge rates. METHODS: This retrospective, propensity-score matched (PSM) case-control study included 180 patients hospitalized with COVID-19 from 3 centers. After assigned in 1:2 ratios by PSM, 33 patients received hydrogen/oxygen therapy and 55 patients received oxygen therapy included in this study. Primary endpoint was the length of hospitalization. Secondary endpoints were hospital discharge rates and oxygen saturation (SpO2). Vital signs and respiratory symptoms were also observed. RESULTS: Findings confirmed a significantly lower median length of hospitalization (HR = 1.91; 95% CIs, 1.25-2.92; p < 0.05) in the hydrogen/oxygen group (12 days; 95% CI, 9-15) versus the oxygen group (13 days; 95% CI, 11-20). The higher hospital discharge rates were observed in the hydrogen/oxygen group at 21 days (93.9% vs. 74.5%; p < 0.05) and 28 days (97.0% vs. 85.5%; p < 0.05) compared with the oxygen group, except for 14 days (69.7% vs. 56.4%). After 5-day therapy, patients in hydrogen/oxygen group exhibited a higher level of SpO2 compared with that in the oxygen group (98.5%±0.56% vs. 97.8%±1.0%; p < 0.001). In subgroup analysis of patients received hydrogen/oxygen, patients aged < 55 years (p = 0.028) and without comorbidities (p = 0.002) exhibited a shorter hospitalization (median 10 days). CONCLUSION: This study indicated that hydrogen/oxygen might be a useful therapeutic medical gas to enhance SpO2 and shorten length of hospitalization in patients with ordinary COVID-19. Younger patients or those without comorbidities are likely to benefit more from hydrogen/oxygen therapy.
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COVID-19 , Humanos , Estudos de Casos e Controles , Estudos Retrospectivos , COVID-19/terapia , Oxigênio/uso terapêutico , Hidrogênio/uso terapêuticoRESUMO
Batch and column leaching tests were used to study thallium's release and migration behaviour and evaluate its potential toxicity risks in soil. The results indicated that leaching concentrations of Tl using TCLP and SWLP were much higher than the threshold, indicating a high risk of thallium pollution in the soil. Furthermore, the intermittent leaching rate of Tl by Ca2+ and HCl reached its maximum value, demonstrating the easy release of Tl. After HCl leaching, the form of Tl in the soil has changed, and ammonium sulfate has increased its extractability. Additionally, the extensive application of calcium promoted the release of Tl, increasing its potential ecological risk. Spectral analysis showed that Tl was mainly present in minerals such as Kaolinite and Jarosite, and exhibited significant adsorption capacity for Tl. HCl and Ca2+ damaged the crystal structure of the soil, greatly enhancing the migration and mobility of Tl in the environment. More importantly, XPS analysis confirmed that the release of Tl (I) in the soil was the leading cause of increased mobility and bioavailability. Therefore, the results revealed the risk of Tl release in the soil, providing theoretical guidance for its pollution prevention and control.
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Keratoconus is one of the most common causes leading to visual impairment in young adult population. The pathogenesis of keratoconus remains poorly understood. The aim of this study was to identify the potential key genes and pathways associated with keratoconus and to further analyze its molecular mechanism. Two RNA-sequencing datasets of keratoconus and paired normal corneal tissues from the Gene Expression Omnibus database were obtained. Differentially expressed genes (DEGs) were identified, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted. The protein-protein interaction (PPI) network of the DEGs was established, and the hub genes and significant gene modules of PPI were further constructed. Lastly, the GO and KEGG analyses of the hub gene were performed. In total, 548 common DEGs were identified. GO enrichment analysis showed that the DEGs were primarily associated with regulation of cell adhesion, the response to molecule of bacterial origin, lipopolysaccharide and biotic stimulus, collagen-containing extracellular matrix, extracellular matrix, and structure organization. KEGG pathway analysis showed that these DEGs were mainly involved in the TNF signaling pathway, IL-17 signaling pathway, Rheumatoid arthritis, Cytokine-cytokine receptor interaction. The PPI network was constructed with 146 nodes and 276 edges, and 3 significant modules are selected. Finally, top 10 hub genes were identified from the PPI network. The results revealed that extracellular matrix remodeling and immune inflammatory response could be the key links of keratoconus, TNF, IL6, IL1A, IL1B, CCL3, MMP3, MMP9, MMP1, and TGFB1 may be potential crucial genes, and TNF signaling pathway and IL-17 signaling pathway were the potential pathways accounting for pathogenesis and development of keratoconus.
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Perfilação da Expressão Gênica , Ceratocone , Humanos , Perfilação da Expressão Gênica/métodos , Interleucina-17/genética , Ceratocone/genética , Mapas de Interação de Proteínas/genética , Expressão Gênica , Biologia Computacional/métodosRESUMO
INTRODUCTION: The aim of this study was to compare the patterns of visual field (VF) defects in primary angle-closure glaucoma (PACG) to control groups of eyes with high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). METHODS: Forty-eight eyes with PACG were enrolled, and control eyes with HTG and NTG matched for age, sex, and mean deviation of VF defect were selected. VF tests were performed using the 24-2 program of the Humphrey field analyzer. VF defects were classified into six patterns with the Ocular Hypertension Treatment Study classification system and were categorized into three stages (early, moderate, and advanced). Each hemifield was divided into five regions according to the Glaucoma Hemifield Test (GHT). The mean total deviation (TD) of each GHT region was calculated. RESULTS: Compared with HTG and NTG groups, the partial arcuate VF defects were more common in the PACG group. In the PACG group, the nasal GHT region in the inferior hemifield had the worst mean TD (-8.48 ± 8.62 dB), followed by the arcuate 1 (-7.81 ± 7.91 dB), arcuate 2 (-7.46 ± 7.43 dB), paracentral (-7.19 ± 7.98 dB), and central (-5.14 ± 6.24 dB) regions; the mean TD of the central region was significantly better than those for all other regions (all p < 0.05). A similar trend was observed in the superior hemifield in the PACG group but not the VF hemifields of the HTG and NTG groups. CONCLUSION: Patterns of VF defect in PACG patients differ from those with HTG and NTG. This discrepancy might be due to the differences in the pathogenic mechanisms of glaucomatous optic neuropathy.
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Glaucoma de Ângulo Fechado , Glaucoma de Ângulo Aberto , Glaucoma , Glaucoma de Baixa Tensão , Humanos , Campos Visuais , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/patologia , Pressão Intraocular , Glaucoma/patologia , Glaucoma de Baixa Tensão/diagnóstico , Testes de Campo Visual , Transtornos da Visão , Células Ganglionares da Retina/patologiaRESUMO
OBJECTIVE: To compare the clinical value and safety of electromagnetic navigation bronchoscopy (ENB) combined with radial endobronchial ultrasound (R-EBUS) or x-ray in the diagnosis of small peripheral pulmonary nodules that cannot be diagnosed by conventional bronchoscopy. METHODS: Fifty-six patients with peripheral pulmonary nodules of <3 cm in diameter who underwent bronchoscopy at the First Affiliated Hospital of Soochow University and Dushu Lake Hospital of Soochow University from February 2019 to January 2022 were selected as the study subjects, including 24 patients who underwent ENB combined with x-ray and 32 patients who underwent ENB combined with R-EBUS. ENB was used as the guiding method in both groups, and x-ray group and R-EBUS group were combined with x-ray and R-EBUS, respectively, to determine whether the lesion was reached. In x-ray group, biopsy and brushing were performed under fluoroscopic guidance. Using the results of surgery, puncture pathology, or clinical follow-up 1 year as the gold standard, the diagnostic sensitivity, specificity, negative predictive value (NPV), diagnostic yield, negative likelihood ratio (LR-), Youden index, missed diagnosis rate, success rate, and κ value were compared between the two groups, and the occurrence of postoperative complications was also compared between the two groups. RESULTS: The negative predictive value of the R-EBUS group was significantly better than that of the x-ray group (p = 0.006). CONCLUSION: Even with smaller nodule diameters, the negative predictive value of ENB combined with R-EBUS were still higher than that of the x-ray group.
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Broncoscopia , Neoplasias Pulmonares , Humanos , Broncoscopia/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Raios X , Biópsia , RadiografiaRESUMO
Human biofluids are often used to discover disease-specific glycosylation, since abnormal changes in protein glycosylation can discern physiopathological states. Highly glycosylated proteins in biofluids make it possible to identify disease signatures. Glycoproteomic studies on saliva glycoproteins showed that fucosylation was significantly increased during tumorigenesis and that glycoproteins became hyperfucosylated in lung metastases, and tumor stage is associated with fucosylation. Quantification of salivary fucosylation can be achieved by mass spectrometric analysis of fucosylated glycoproteins or fucosylated glycans; however, the use of mass spectrometry is non-trivial for clinical practice. Here, we developed a high-throughput quantitative method, lectin-affinity fluorescent labeling quantification (LAFLQ), to quantify fucosylated glycoproteins without relying on mass spectrometry. Lectins with a specific affinity for fucoses are immobilized on the resin and effectively capture fluorescently labeled fucosylated glycoproteins, which are further quantitatively characterized by fluorescence detection in a 96-well plate. Our results demonstrated that serum IgG can be accurately quantified by lectin and fluorescence detection. Quantification in saliva showed significantly higher fucosylation in lung cancer patients compared to healthy controls or other non-cancer diseases, suggesting that this method has the potential to quantify stage-related fucosylation in lung cancer saliva.
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So far, the studies exploring plasma α-synuclein as a biomarker of Parkinson's disease (PD) have provided contradictory results. Here, we first employed the Mendelian randomization (MR) approach to elucidate their potential causal relationship. Five genetic instrumental variables of plasma α-synuclein were acquired from two publicly available datasets. Three independent genome-wide association studies of PD were used as outcome cohorts (PD cohorts 1, 2, and 3). Two-sample MR analyses were conducted using inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, and leave-one-out methods. Though the IVW approach demonstrated positive plasma α-synuclein effect on the PD risk in three outcome cohorts (OR = 1.134, 1.164, and 1.189, respectively), the P values were all larger than 0.05. The conclusions were robust under complementary sensitivity analyses. Our results did not support the causal relationship between plasma α-synuclein and PD.
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Doença de Parkinson , Humanos , Doença de Parkinson/genética , alfa-Sinucleína/genética , Análise da Randomização Mendeliana/métodos , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Human body fluids have become an indispensable resource for clinical research, diagnosis and prognosis. Urine is widely used to discover disease-specific glycoprotein biomarkers because of its recurrently non-invasive collection and disease-indicating properties. While urine is an unstable fluid in that its composition changes with ingested nutrients and further as it is excreted through micturition, urinary proteins are more stable and their abnormal glycosylation is associated with diseases. It is known that aberrant glycosylation can define tumor malignancy and indicate disease initiation and progression. However, a thorough and translational survey of urinary glycosylation in diseases has not been performed. In this article, we evaluate the clinical applications of urine, introduce methods for urine glycosylation analysis, and discuss urine glycoprotein biomarkers. We emphasize the importance of mining urinary glycoproteins and searching for disease-specific glycosylation in various diseases (including cancer, neurodegenerative diseases, diabetes, and viral infections). With advances in mass spectrometry-based glycomics/glycoproteomics/glycopeptidomics, characterization of disease-specific glycosylation will optimistically lead to the discovery of disease-related urinary biomarkers with better sensitivity and specificity in the near future.
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Líquidos Corporais , Neoplasias , Humanos , Glicosilação , Glicoproteínas/metabolismo , Processamento de Proteína Pós-Traducional , Biomarcadores/metabolismo , Líquidos Corporais/metabolismo , Neoplasias/diagnósticoRESUMO
PRCIS: Health examination center-based screening provide a good supplement to clinic-based glaucoma care by detecting early-stage glaucoma, especially those with normal intraocular pressure (IOP) and less visual impairment. PURPOSE: Opportunistic glaucoma screening for early case identification is of great value in the prevention of severe visual impairment, however, novel, low-cost models are needed. We aimed to determine whether health examination center-based glaucoma screening identifies diseases earlier than outpatient cases in China. MATERIALS AND METHODS: In this case-control study, 76 patients with primary glaucoma identified from a health examination center-based glaucoma screening program and 272 consecutive outpatient cases at the same hospital were enrolled from March 21 to September 30, 2016. Demographic characteristics, best-corrected visual acuity, IOP, mean deviation (MD), and pattern standard deviation (PSD) on Humphrey visual field testing in the better-seeing eye were compared between groups. RESULTS: Screening-detected glaucoma patients had significantly lower IOP (18.3±4.2 mm Hg) than out-patient cases (26.7±12.6 mm Hg, P <0.001). Most (71.1%) of the screening-detected patients had IOP<21 mm Hg compared with 37.1% in the clinic group ( P <0.001). Seventy-five patients (98.7%) in the screening group were diagnosed as primary open angle glaucoma, compared with 44.1% in the clinic group ( P <0.001). Screening-detected patients had significantly less visual impairment than the clinic group (6.6% vs. 38.6%, P <0.05). Mean MD (-4.4±5.0 dB) and PSD (4.4±3.6 dB) for the screening group were superior to the clinic group (MD: -16.5±10.5 dB, P <0.001; PSD: 6.5±3.7 dB, P <0.001). CONCLUSION: The glaucoma screening program was effective at detecting early disease, especially normal tension glaucoma and supplemented opportunistic detection of glaucoma.
Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Baixa Visão , Humanos , Glaucoma de Ângulo Aberto/diagnóstico , Pressão Intraocular , Estudos de Casos e Controles , Glaucoma/diagnóstico , Testes de Campo Visual , Transtornos da Visão , China/epidemiologiaRESUMO
Doublesex and Mab-3 related Transcription Factor 3 (DMRT3) is associated with the prognosis of some tumors. It is possible to explore the role of DMRT3 in the cancer process using bioinformatic approaches and experimental validation. We comprehensively explored the clinical and immunological characteristics of DMRT3. The DMRT3 expression is abnormal in human cancers and correlates with clinical staging. A high DMRT3 expression is significantly associated with poor overall survival (OS) in KIRC, KIRP, LUAD, and UCEC. Amplification was the greatest frequency of the DMRT3 alterations in pan-cancer. The OS was significantly lower in the DMRT3 altered group than in the DMRT3 unaltered group (P = 0.0276). The DMRT3 expression was significantly associated with MSI in three cancer types and TMB in six cancer types. The DMRT3 expression was significantly correlated with the level of the immune cell infiltration and the immune checkpoint genes. The DMRT3 was involved in some pathways in pan-cancer. DMRT3 may play a role in chemotherapy and may be associated with chemoresistance. A ceRNA network of KCNQ1OT1/miR-335-5p/DMRT3 was constructed in LUAD. DMRT3 was significantly upregulated in the LUAD cell lines. DMRT3 was aberrantly expressed in pan-cancer and may promote tumorigenesis and progression via different mechanisms. DMRT3 can be used as a therapeutic target to treat cancer in humans.