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BACKGROUND: Hypoxia is a major cause and promoter of pulmonary hypertension (PH), a representative vascular remodeling disease with poor prognosis and high mortality. However, the mechanism underlying how pulmonary arterial system responds to hypoxic stress during PH remains unclear. Endothelial mitochondria are considered signaling organelles on oxygen tension. Results from previous clinical research and our studies suggested a potential role of posttranslational SUMOylation (small ubiquitin-like modifier modification) in endothelial mitochondria in hypoxia-related vasculopathy. METHODS: Chronic hypoxia mouse model and Sugen/hypoxia rat model were employed as PH animal models. Mitochondrial morphology and subcellular structure were determined by transmission electron and immunofluorescent microscopies. Mitochondrial metabolism was determined by mitochondrial oxygen consumption rate and extracellular acidification rate. SUMOylation and protein interaction were determined by immunoprecipitation. RESULTS: The involvement of SENP1 (sentrin-specific protease 1)-mediated SUMOylation in mitochondrial remodeling in the pulmonary endothelium was identified in clinical specimens of hypoxia-related PH and was verified in human pulmonary artery endothelial cells under hypoxia. Further analyses in clinical specimens, hypoxic rat and mouse PH models, and human pulmonary artery endothelial cells and human embryonic stem cell-derived endothelial cells revealed that short-term hypoxia-induced SENP1 translocation to endothelial mitochondria to regulate deSUMOylation (the reversible process of SUMOylation) of mitochondrial fission protein FIS1 (mitochondrial fission 1), which facilitated FIS1 assembling with fusion protein MFN2 (mitofusin 2) and mitochondrial gatekeeper VDAC1 (voltage-dependent anion channel 1), and the membrane tethering activity of MFN2 by enhancing its oligomerization. Consequently, FIS1 deSUMOylation maintained the mitochondrial integrity and endoplasmic reticulum-mitochondria calcium communication across mitochondrial-associated membranes, subsequently preserving pulmonary endothelial function and vascular homeostasis. In contrast, prolonged hypoxia disabled the FIS1 deSUMOylation by diminishing the availability of SENP1 in mitochondria via inducing miR (micro RNA)-138 and consequently resulted in mitochondrial dysfunction and metabolic reprogramming in pulmonary endothelium. Functionally, introduction of viral-packaged deSUMOylated FIS1 within pulmonary endothelium in mice improved pulmonary endothelial dysfunction and hypoxic PH development, while knock-in of SUMO (small ubiquitin-like modifier)-conjugated FIS1 in mice exaggerated the diseased cellular and tissue phenotypes. CONCLUSIONS: By maintaining endothelial mitochondrial homeostasis, deSUMOylation of FIS1 adaptively preserves pulmonary endothelial function against hypoxic stress and consequently protects against PH. The FIS1 deSUMOylation-SUMOylation transition in pulmonary endothelium is an intrinsic pathogenesis of hypoxic PH.
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Hipertensão Pulmonar , Doenças Vasculares , Humanos , Camundongos , Ratos , Animais , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/prevenção & controle , Células Endoteliais , Mitocôndrias , Modelos Animais de Doenças , Endotélio , Ubiquitinas , Proteínas de Membrana , Proteínas MitocondriaisRESUMO
Angiogenesis contributes fundamentally to embryonic development, tissue homeostasis, and wound healing. Basic fibroblast growth factor (FGF2) is recognized as the first proangiogenic molecule discovered, and it facilitates angiogenesis by activating FGF receptor 1 (FGFR1) signaling in endothelial cells. However, the precise roles of FGFR and the FGF/FGFR signaling axis in angiogenesis remain unclear, especially because of the contradictory phenotypes of in vivo FGF and FGFR gene deficiency models. Our previous study results suggested a potential role of posttranslational small ubiquitin-like modifier modification (SUMOylation), with highly dynamic regulatory features, in vascular development and disorder. Here, we identified SENP1-regulated endothelial FGFR1 SUMOylation at conserved lysines responding to proangiogenic stimuli, while SENP1 functioned as the deSUMOylase. Hypoxia-enhanced FGFR1 SUMOylation restricted the tyrosine kinase activation of FGFR1 by modulating the dimerization of FGFR1 and FGFR1 binding with its phosphatase PTPRG. Consequently, it facilitated the recruitment of FRS2α to VEGFR2 but limited additional recruitment of FRS2α to FGFR1, supporting the activation of VEGFA/VEGFR2 signaling in endothelial cells. Furthermore, SUMOylation-defective mutation of FGFR1 resulted in exaggerated FGF2/FGFR1 signaling but suppressed VEGFA/VEGFR2 signaling and the angiogenic capabilities of endothelial cells, which were rescued by FRS2α overexpression. Reduced angiogenesis and endothelial sprouting in mice bearing an endothelial-specific, FGFR1 SUMOylation-defective mutant confirmed the functional significance of endothelial FGFR1 SUMOylation in vivo. Our findings identify the reversible SUMOylation of FGFR1 as an intrinsic fine-tuned mechanism in coordinating endothelial angiogenic signaling during neovascularization; SENP1-regulated FGFR1 SUMOylation and deSUMOylation controls the competitive recruitment of FRS2α by FGFR1 and VEGFR2 to switch receptor-complex formation responding to hypoxia and normoxia angiogenic environments.
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Células Endoteliais , Neovascularização Fisiológica , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Sumoilação , Animais , Células Endoteliais/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Hipóxia/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Mutação , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais , Sumoilação/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: Adverse events of secondary adrenal insufficiency caused by anti-PD-1 immune agents are relatively rare in clinical practice, so in this article, we retrospectively analyzed three patients who suffered secondary adrenal cortex dysfunction caused by tislelizumab immunotherapy for Non-Small Cell Lung Cancer (NSCLC)and reviewed the literature. This rare immune-related adverse event was investigated by summarizing the clinical features of the patients. CASE PRESENTATION: We reported three NSCLC patients who suffered secondary adrenal cortex dysfunction induced by tislelizumab immunotherapy at our hospital from July 2021 to October 2023. We analyzed and summarized the clinical characteristic, laboratory examination, pathological staging, etc. We also reviewed related literature of pituitary inflammation and adrenal cortex dysfunction caused by immunotherapy. RESULTS: The median age of the three patients was 56 years. All the patients had a history of smoking. After receiving tislelizumab treatment (median cycle: 7), laboratory examination showed a decrease in morning cortisol and adrenocorticotropic hormone (ACTH), both were diagnosed with secondary adrenal insufficiency. Only one patient had symptoms of fatigue, vomiting, and weight loss. One of these patients also had simultaneous subclinical hypothyroidism. All three patients discontinued immunotherapy and received replacement therapy with glucocorticoids. At the last follow-up, none of the three patients restarted immunotherapy, because cortisol did not return to normal. This is similar to that of previous reports. CONCLUSION: Based on previous reports and our three cases, when laboratory tests of NSCLC patients receiving immunotherapy showed a decrease in morning cortisol and ACTH levels, especially when clinical symptoms were obvious, the possibility of immunotherapy-related pituitary inflammation causing secondary adrenal cortex dysfunction should be considered. Prompt monitoring and hormone replacement therapy should be provided to prevent adrenal crises.
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Insuficiência Adrenal , Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Masculino , Insuficiência Adrenal/induzido quimicamente , Feminino , Imunoterapia/efeitos adversos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Antineoplásicos Imunológicos/efeitos adversos , Estudos Retrospectivos , Idoso , Hormônio AdrenocorticotrópicoRESUMO
Oxysophoridine (OSR) is a main active alkaloid extracted from Sophora alopecuroides, which is a traditional Chinese herbal medicine that has been used widely. In this study, we used thoracic aorta rings isolated from Sprague-Dawley rats to explore the vasodilative activity of OSR and its potential mechanisms. The isolated rat thoracic aorta rings were used to observe the effects of different concentrations of OSR (0.4-2.0 g·L-1) on the resting normal rings and the phenylephrine precontracted endothelium-intact or endothelium-denudedisolated thoracic aorta rings, respectively. The interactions among OSR and barium chloride (BaCl2), tetraethylamine, 4-aminopyridine, glibenclamide (Gli), L-nitroarginine methyl ester (L-NAME), and cyclooxygenase (COX) inhibitor indomethacin (INDO) were evaluated. The experimental results show that OSR had no effect on the tension of resting vascular rings, but the vasodilating effect could be confirmed in a concentration-dependent manner on both endothelium-intact and endothelium-denuded vascular rings. This vasodilation effect of OSR on thoracic aorta vascular rings could be inhibited significantly by potassium channel blockers glibenclamide (Gli, 10 µmol·L-1) and 4-aminopyridine (4-AP, 5 mmol·L-1). In addition, vasodilatory effects of OSR were not inhibited in the presence of potassium channel blockers barium chloride (BaCl2, 1 mmol·L-1) and tetraethylamine (TEA, 10 mmol·L-1), nitric oxide synthase inhibitor (L-NAME, 0.1 mmol·L-1) and COX inhibitor (INDO, 10 µmol·L-1). In conclusion, the vasodilatory effects of OSR on thoracic aorta rings is associated with KV and KATP.
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Alcaloides , Vasodilatação , Alcaloides/farmacologia , Animais , Aorta Torácica , NG-Nitroarginina Metil Éster/farmacologia , Ratos , Ratos Sprague-Dawley , Vasodilatadores/farmacologiaRESUMO
BACKGROUND To study the role of the long-chain noncoding RNA (lncRNA) metastasis-related lung adenocarcinoma transcript 1 (MALAT1), microRNA-503 (miR-503), Toll-like receptor 4 (TLR4) signal axis in the pathogenesis of pulmonary arterial hypertension (PAH). MATERIAL AND METHODS Total RNA was extracted from the plasma of 45 PAH patients and 45 healthy subjects, and the expression of lncRNA MALAT1 and miR-503 was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of lncRNA MALAT1 and miR-503 on Toll-like receptor 4 (TLR4) and the proliferation, migration, and apoptosis of human pulmonary artery smooth muscle cells (hPASMCs) were tested following in vitro transfection of hPASMCs. RESULTS lncRNA MALAT1 was highly expressed in the plasma of PAH patients and in hypoxia-induced hPASMCs. Silencing lncRNA MALAT1 inhibited the proliferation and migration of hPASMC cells while promoting their apoptosis. MiR-503 is underexpressed in plasma and hPASMCs of patients with PAH. TLR4 was a target gene of miR-503 and was highly expressed in peripheral blood mononuclear cells (PBMCs) of PAH patients. lncRNA MALAT1 was a "molecular sponge" of miR-503, regulating the expression of TLR4 and the proliferation, migration, and apoptosis of hPASMCs through miR-503. CONCLUSIONS lncRNA MALAT1 promotes the proliferation and migration of hPASMCs and inhibits their apoptosis by inhibiting the miR-503/TLR4 signal axis.
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MicroRNAs/genética , Hipertensão Arterial Pulmonar/patologia , RNA Longo não Codificante/genética , Adulto , Idoso , Apoptose/genética , Hipóxia Celular/genética , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Miócitos de Músculo Liso/metabolismo , Hipertensão Arterial Pulmonar/genética , Hipertensão Arterial Pulmonar/metabolismo , Artéria Pulmonar/metabolismo , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , Transdução de Sinais , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismoRESUMO
Quinone methide (QM) as a latent trapping unit has been widely explored in activity-based self-immobilizing reagents. However, further application of this strategy has been largely hampered by the limited labeling efficiency to proteins. In this study, a thorough investigation on the labeling efficiency and the structure of QM-based trapping unit is presented, from which a QM with multiple leaving groups was identified as an optimal trapping unit. An alkaline phosphatase (ALP) immobilizing reagent featured with this multiple-labeling trapping unit exhibited lower nonspecific binding and, remarkably, a significantly higher labeling efficiency over other immobilizing reagents upon enzymatic activation. The utility of this imaging reagent was further demonstrated with the in vitro and in vivo visualization of the ALP activities. Furthermore, the multiple functional trapping unit may find greater value in the other activity-based immobilizing probes.
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Fosfatase Alcalina/metabolismo , Indolquinonas/química , Fosfatase Alcalina/química , Animais , Corantes Fluorescentes/química , Células HEK293 , Células HeLa , Humanos , Indolquinonas/metabolismo , Camundongos , Camundongos Nus , Microscopia de Fluorescência , Imagem Óptica , Coloração e Rotulagem , Transplante HeterólogoRESUMO
An efficient copper-mediated ortho-C(sp2)-H thiolation of aromatic amides directed by a novel directing group [4-chloro-2-(1H-pyrazol-1-yl)phenyl]amine has been developed without the need of other additives or oxidants, allowing for an increased usefulness. With the high compatibility of sterically demanding substrates, this reaction is scalable and can tolerate a wide scope of functional groups to provide alkyl and aryl thioethers in good to excellent yields (up to 93%). Furthermore, the protocol has been successfully implemented for the selenylation as well.
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Bronchopleural fistula (BPF) is a potentially fatal complication and remains a surgical challenge. Concomitant problems, such as pulmonary infection and respiratory failure, are typically the main contributors to mortality from BPF because of improper contact between the bronchial and pleural cavity. We present the case of a 75-year-old male patient with a history of right upper lobe lung cancer resection who developed complex BPFs. Following appropriate antibiotic therapy and chest tube drainage, we treated the fistulas using endobronchial valve EBV placement and local argon gas spray stimulation. Bronchoscopic treatment is the preferred method for patients who cannot tolerate a second surgery because it can help to maximize their quality of life. Our treatment method may be a useful reference for treating complex BPF.
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Fístula Brônquica , Doenças Pleurais , Masculino , Humanos , Idoso , Qualidade de Vida , Broncoscopia/efeitos adversos , Fístula Brônquica/diagnóstico por imagem , Fístula Brônquica/etiologia , Fístula Brônquica/cirurgia , Doenças Pleurais/diagnóstico por imagem , Doenças Pleurais/etiologia , Doenças Pleurais/cirurgia , Antibacterianos/uso terapêuticoRESUMO
Introduction: This study investigated the impact of competition on supplier-induced demand in medical markets theoretically and experimentally. Methods: We employed the framework of credence goods to describe the information asymmetry between physicians and patients, and theoretically derives predictions of physicians' behaviors in monopolistic and competitive markets. Then we conducted behavioral experiments to empirically test the hypotheses. Results: The theoretical analysis revealed that an honest equilibrium would not exist in a monopolistic market, whereas price competition could induce physicians to reveal their types of treatment cost and provide honest treatments; thus, a competitive equilibrium is superior to that of a monopolistic market. The experimental results only partially supported the theoretical predictions, which showed that the cure rate of patients in a competitive environment was higher than that in a monopolistic market, although supplier-induced demand occurred more frequently. In the experiment, the main channel through which competition improved market efficiency was increased patient consultations through low pricing, as opposed to the theory, which stated that competition would lead to physicians' honest treatment of patients through fair prices. Discussion: We discovered that the divergence between the theory and the experiment stemmed from the theory's reliance on the assumption that humans are rational and self-interested, which means that they are not as price-sensitive as predicted by theory.
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Competição Econômica , Demanda Induzida , Humanos , Custos e Análise de CustoRESUMO
Unethical behavior is discovered that is more contagious than ethical behavior. This article attempts to propose one of the possible underlying mechanisms-people may have underconfidence bias in information updating due to motivated reasoning, and such bias exhibits in a different direction compared to the overconfident bias documented in the literature on ethical environment, which generate the asymmetric pattern in contagion. This study designs an experiment which relates the unethical behavior to social learning, where a series of subjects with private information about penalty decide sequentially whether to conduct unethical behavior publicly. This study adopts a quantal response equilibrium to construct a structural model for estimation of the bias. In total, 162 university students participated in our experiment and the results confirm the asymmetric patterns that people rely more on others' precedent decisions rather than their private signal; therefore, the bias facilitates the contagion. This study also tests two punishment systems in the experiment and the results suggest a policy: slightly increasing penalties for the "followers" in the early stages would effectively suppress the contagion.
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Branched-chain amino acids (BCAAs), including valine, leucine, and isoleucine, are crucial amino acids with significant implications in tumorigenesis across various human malignancies. Studies have demonstrated that altered BCAA metabolism can influence tumor growth and progression. Increased levels of BCAAs have been associated with tumor growth inhibition, indicating their potential as anti-cancer agents. Conversely, a deficiency in BCAAs can promote tumor metastasis to different organs due to the disruptive effects of high BCAA concentrations on tumor cell migration and invasion. This disruption is associated with tumor cell adhesion, angiogenesis, metastasis, and invasion. Furthermore, BCAAs serve as nitrogen donors, contributing to synthesizing macromolecules such as proteins and nucleotides crucial for cancer cell growth. Consequently, BCAAs exhibit a dual role in cancer, and their effects on tumor growth or inhibition are contingent upon various conditions and concentrations. This review discusses these contrasting findings, providing valuable insights into BCAA-related therapeutic interventions and ultimately contributing to a better understanding of their potential role in cancer treatment.
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Evidence demonstrated that bones, liver, and lungs are the most common metastasis sites in some human malignancies, especially in prostate and breast cancers. Bone is the third most frequent target for spreading tumor cells among these organs and tissues. Patients with bone-metastatic cancers face a grim prognosis characterized by short median survival time. Current treatments have proven insufficient, as they can only inhibit metastasis or tumor progression within the bone tissues rather than providing a curative solution. Gaining a more profound comprehension of the interplay between tumor cells and the bone microenvironment (BME) is of utmost importance in tackling this issue. This knowledge will pave the way for developing innovative diagnostic and therapeutic approaches. This review summarizes the mechanisms underlying bone metastasis and discusses the clinical aspects of this pathologic condition. Additionally, it highlights emerging therapeutic interventions aimed at enhancing the quality of life for patients affected by bone-metastatic cancers. By synthesizing current research, this review seeks to shed light on the complexities of bone metastasis and offer insights for future advancements in patient care.
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Neoplasias Ósseas , Neoplasias da Mama , Masculino , Humanos , Qualidade de Vida , Neoplasias Ósseas/terapia , Osso e Ossos , Conhecimento , Microambiente TumoralRESUMO
Porous carbon nitride/bismuth oxychloride (PCN/BiOCl-x) polymer-based heterojunction photocatalysts were successfully synthesized via a simple in situ hydrothermal method. A PCN/BiOCl heterojunction with rich chlorine defects is prepared by adjusting the chlorine content of the BiOCl unit in the heterojunction by changing the solvent. The as-prepared catalysts were characterized via BET, SEM, TEM, XRD, XPS and optical testing, and they were used for a photocatalytic amine oxidation reaction. The results indicated that the catalytic performance of the PCN/BiOCl heterojunction was significantly enhanced due to the rich chlorine vacancies in the samples. The enhanced catalytic activity may be attributed to the Z-scheme heterojunction, abundant chlorine defects and large specific surface area. At the same time, the catalyst circulation experiment shows that the PCN/BiOCl heterojunction has good circulation performance.
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RATIONALE: Schizophyllum commune (S. commune) is a basidiomycete bracket fungus that rarely causes invasive fungal infections. It is often misdiagnosed as other invasive fungal disease because of its atypical clinical features. Here we report a case of pneumonia due to S commune and review the relevant literature. PATIENT CONCERNS AND DIAGNOSES: A 55-year-old male with a history of diabetes and poor glycemic control presented with cough and sputum for half a month. Laboratory examination showed elevated peripheral blood eosinophils, bronchoalveolar lavage fluid eosinophils and increased serum total immunoglobulin E. Chest computed tomography revealed a gloved finger sign and consolidation in the middle lobe of the right lung and the upper lobe of the left lung. Bronchoscopy revealed thick white mucous plugs in the left lingular bronchus, which could be removed partially by suctioning. The culture of bronchoalveolar lavage fluid and bronchoscopy brush specimens grew cottony white mold in sabouraud dextrose agar. Pneumonia caused by S. commune was diagnosed based on clinical features and microbial methods. INTERVENTIONS AND OUTCOMES: Voriconazole combined with inhaled budesonide and formoterol (inhaled corticosteroids + long-acting ß-2 receptor agonist) were given, and his symptoms improved. The count of peripheral blood eosinophils and serum total immunoglobulin E decreased after 1 month. Repeated chest computed tomography showed remarkable improvement over the previous lesions. LESSONS: Although rarely reported, infections in the lungs caused by S commune should be reminded especially in patients with immunocompromised. This case illustrates the risk factors, clinical symptoms and imaging features of the pneumonia caused by S. commune. It also further highlights the diagnosis and treatment of this disease through reviewing relevant literature.
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Diabetes Mellitus , Pneumonia , Schizophyllum , Masculino , Humanos , Pessoa de Meia-Idade , Pulmão/patologia , Brônquios , Pneumonia/patologia , Diabetes Mellitus/patologiaRESUMO
By predicting ERα bioactivity and mining the potential relationship between Absorption, Distribution, Metabolism, Excretion, Toxicity (ADMET) attributes in drug research and development, the development efficiency of specific drugs for breast cancer will be effectively improved and the misjudgment rate of R&D personnel will be reduced. The quantitative prediction model of ERα bioactivity and classification prediction model of Absorption, Distribution, Metabolism, Excretion, Toxicity properties were constructed. The prediction results of ERα bioactivity were compared by XGBoot, Light GBM, Random Forest and MLP neural network. Two models with high prediction accuracy were selected and fused to obtain ERα bioactivity prediction model from Mean absolute error (MAE), mean squared error (MSE) and R2. The data were further subjected to model-based feature selection and FDR/FPR-based feature selection, respectively, and the results were placed in a voting machine to obtain Absorption, Distribution, Metabolism, Excretion, Toxicity classification prediction model. In this study, 430 molecular descriptors were removed, and finally 20 molecular descriptors with the most significant effect on biological activity obtained by the dual feature screening combined optimization method were used to establish a compound molecular descriptor prediction model for ERα biological activity, and further classification and prediction of the Absorption, Distribution, Metabolism, Excretion, Toxicity properties of the drugs were made. Eighty variables were selected by the model ExtraTreesClassifier Classifie, and 40 variables were selected by the model GradientBoostingClassifier to complete the model-based feature selection. At the same time, the feature selection method based on FDR/FPR is also selected, and the three classification models obtained by the two methods are placed into the voting machine to obtain the final model. The experimental results showed that the model's evaluation indexes and roc diagram were excellent and could accurately predict ERα bioactivity and Absorption, Distribution, Metabolism, Excretion, Toxicity properties. The model constructed in this study has high accuracy, fast convergence and robustness, has a very high accuracy for Absorption, Distribution, Metabolism, Excretion, Toxicity and ERα classification prediction, has bright prospects in the biopharmaceutical field, and is an important method for energy conservation and yield increase in the future.
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BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a valuable tool for diagnosing pulmonary disease due to its efficiency and safety. We retrospectively analyzed patients with mediastinal masses who underwent diagnostic EBUS-TBNA at Shanghai Chest Hospital, and evaluated the clinical accuracy of EBUS-TBNA in the diagnosis mediastinal masses. METHOD: From 2009 and 2014, patients who received EBUS-TBNA to diagnose a isolated mediastinal mass were enrolled. Clinical follow-up was performed to ascertain the patient's final diagnosis. RESULTS: Forty-six patients were enrolled in this study. Thirty-seven were diagnosed with an oncologic disease, 3 were diagnosed with a mediastinal infection, and 2 were found to have a mediastinal goiter. The overall sensitivity, specificity, positive predictive value, negative predictive value, diagnostic yield was 63.6%, 100%, 100%, 42.9%, and 71.4%, respectively. CONCLUSION: EBUS-TBNA is a safe and effective means of diagnosing mediastinal masses.
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ABSTRACT: The PITX gene family of transcription factors have been reported to regulate the development of multiple organs. This study was designed to investigate the role of PITXs in lung adenocarcinoma (LUAD).In this study, the transcriptional levels of the 3 identified PITXs in patients with LUAD were examined using the gene expression profiling interactive analysis interactive web server. Meanwhile, the immunohistochemical data of the 3 PITXs were obtained in the Human Protein Atlas website, and western blotting was additionally conducted for further verification. Moreover, the association between the levels of PITXs and the stage plot as well as overall survival of patients with LUAD was analyzed.We found that the mRNA and protein levels of PITX1 and PITX2 were higher in LUAD tissues than those in normal lung tissues, while those of PITX3 displayed no significant differences. Additionally, PITX1 and PITX3 were found to be significantly associated with the stage of LUAD. The Kaplan-Meier Plot showed that the high level of PITX1 conferred a better overall survival of patients with LUAD while the high level of PITX3 was associated with poor prognosis.Our study implied that PITX1 and PITX3 are potential targets of precision therapy for patients with LUAD while PITX1 and PITX2 are regarded as novel biomarkers for the diagnosis of LUAD.
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Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/patologia , Fatores de Transcrição Box Pareados/genética , Biomarcadores Tumorais , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Humanos , Estimativa de Kaplan-Meier , Prognóstico , RNA Mensageiro , Fatores de Transcrição/genética , Proteína Homeobox PITX2RESUMO
In this work, a PCN/Fe2O3/CdS ternary heterojuction photocatalyst was constructed by introducing an appropriate amount of ferric oxide (Fe2O3) and cadmium sulfide (CdS) onto porous carbon nitride (PCN), denoted as PCN/Fe2O3/CdS. In the presence of PCN/Fe2O3/CdS, the turnover frequency value and selectivity of the oxidative coupling reaction of benzylamine were 6740 µmol g-1 h-1 and 99.4%, respectively. The excellent catalytic performance of the PCN/Fe2O3/CdS photocatalyst is attributed to fully exposed active sites due to the porous structure of PCN, improved light utilization efficiency by introduction of Fe2O3 and CdS, and increased mobility of e--h+ pairs by construction of a ternary heterostructure, and was proved by the analysis of its structural and optical properties. According to the substrate scope study and Hammett diagram analysis, the rate determining step of the benzylamine self-coupling reaction photocatalyzed by PCN/Fe2O3/CdS was the condensation of imine and benzylamine into N-benzylidenebenzylamine. The results of the free radical quenching experiment and electron spin resonance tests showed that h+ played a major role in the photoreaction process, followed by ËO2- and ËOH. After four photocatalytic reaction cycles, the catalytic performance of the PCN/Fe2O3/CdS heterojunction composite material remained good. Finally, combined with the free radical trapping experiment and energy band structure analysis, a possible double Z-type reaction mechanism was proposed.
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Reported herein is a regioselective difluoromethane sulfonylation or triflylation of resorufin derivatives, which allows easy access to 2-difluoromethane sulfonylated or triflylated resorufin derivatives in good yields. The installation of a difluoromethane sulfonyl group significantly increases the solubility of the chromophore and expands its Stokes shift. A difluoromethane sulfonylated resorufin-based fluorogenic probe proved to be able to image enzyme activity in live cells with a stronger fluorescence signal compared with its resorufin counterpart.
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A recent outbreak of pneumonia in Wuhan, China, was caused by the 2019 novel coronavirus (2019-nCoV). There have been some reports of imaging findings regarding the disease's characteristic features. Here, we report three cases of coronavirus disease 2019 (COVID-19) with dynamic pulmonary CT evaluation. The CT scan showed multiple regions of ground-glass opacities and patchy consolidation in COVID-19 patients and the CT scan was useful in tracking the progression or regression of COVID-19.