The Relationship of Fractional Exhaled Nitric Oxide in Patients with AECOPD.

Objective: To identify the relationship between patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and their fractional-exhaled nitric oxide (FeNO) levels. Methods: Patients diagnosed with AECOPD in the respiratory department of Beijing Chaoyang Hospital from June 2017 to August 2019 were recorded. The demographic data, FeNO value, peripheral blood eosinophil count, number of acute exacerbations in the past year, pulmonary function test, use of inhaled glucocorticoids (ICS) and other data were collected and analyzed. FeNO was measured again three months after discharge, the participants were assessed to determine if the stable period criteria were met. Results: A total of 214 patients met the requirements of this study. 25ppb for FeNO was used as the cutoff for further analysis. The proportion of males, number of acute exacerbations in the past year, number of ICS users, leukocyte count and eosinophil count in the high FeNO-level group was significantly higher than that in the low-level group (P < 0.05). The results showed that the number of acute exacerbations in the past year, number of ICS users, and eosinophil count were statistically significant in the model (P < 0.05). The study also showed that the level of FeNO in the acute exacerbation phase was significantly higher than that in the stable phase. The ROC curve that the area under the curve used by FeNO to predict ICS used is 0.631 (95% CI: 0.526-0.736), and the corresponding P value is 0.022. Conclusion: FeNO is closely related to activated T2 inflammation and eosinophil count in COPD patients. The FeNO levels can be used as an index to evaluate the severity of COPD and predict the recovery of activity after ICS treatment. FeNO can predict the use of ICS and is a beneficial supplement to eosinophils.

Autofluorescence imaging-assisted medical thoracoscopy in the diagnosis of malignant pleural disease.

BACKGROUND: Medical thoracoscopy (MT) does not always provide a conclusive diagnosis of pleural diseases because the endoscopic appearance of pleural diseases can be misleading. Autofluorescence imaging (AFI) is an effective assistive diagnostic tool. However, its clinical application for pleural disease remains controversial. OBJECTIVES: This prospective study evaluated the clinical usefulness of AFI-assisted MT for diagnosis of malignant pleural diseases. METHODS: Patients with unexplained pleural effusion admitted to our clinics between December 2018 and September 2021 were enrolled. We performed white-light thoracoscopy (WLT) first, and then AFI, during MT. Images of endoscopic real-time lesions were recorded under both modes. Pleural biopsy specimens were analyzed pathologically. Between-groups differences in diagnostic sensitivity, specificity, positive-predictive value (PPV), and negative-predictive value (NPV) were assessed using 95% confidence intervals (CI). Receiver operating characteristic curves and decision curve analyses were employed to analyze the diagnostic efficiency of these two modes. RESULTS: Of 126 eligible patients, 73 cases were diagnosed with malignant pleural disease. A total of 1292 biopsy specimens from 492 pleural sites were examined for pathological changes. The diagnostic sensitivity, PPV, and NPV of AFI were 99.7%, 58.2%, and 99.2%, respectively. AFI was significantly superior to WLT, which had a sensitivity of 79.7%, PPV of 50.7%, and NPV of 62.8%. Subgroup analysis showed that the AFI type III pattern was significantly more specific for pleural malignant disease than that of WLT. CONCLUSIONS: AFI could further improve the diagnostic efficacy of MT by providing better visualization, convenience, and safety.

Is conventional transbronchial lung biopsy out: The evaluation of clinical value in diffuse parenchymal lung disease.

INTRODUCTION: Transbronchial lung biopsy (TBLB) is a relatively safe technique routinely employed by pulmonologists for the diagnosis of diffuse parenchymal lung disease (DPLD). Cryobiopsy is associated with higher diagnostic yield and a favorable risk/benefit ratio. Nevertheless, TBLB remains the representative method for definite diagnosis in developing countries. OBJECTIVES: This study aimed to evaluate whether the results obtained from TBLB had clinical value to pulmonologists in the management of DPLD. METHODS: We performed a retrospective analysis of patients who underwent conventional TBLB for the diagnosis of DPLD from May 1, 2017, to April 30, 2019, at the Beijing Chao-yang Hospital, Capital Medical University. The clinical value of TBLB was defined as leading to a specific histopathological diagnosis or being consistent with the clinical and radiological data. RESULTS: Seven hundred and forty-three patients with suspected DPLD were recruited. Conventional TBLB was considered clinically valuable in 439 procedures (59.1%), including 360 cases provided with definitive histopathological diagnoses, and 79 cases that were consistent with the working diagnoses. Among the 439 cases of clinically valuable TBLBs, 88 (20.0%), 37, 77 (10.7%), and 61 (13.9%) cases were diagnosed as connective tissue disease-related interstitial lung disease, definite histopathological diagnoses, malignancies, and nonspecific interstitial pneumonia, respectively. CONCLUSIONS: Conventional TBLB served as a key determinant or provided supplementary information in the final diagnosis of non-infectious DPLDs. TBLB decision-making should therefore be based on clinical and radiological data.

"Plug and Play" logic gate construction based on chemically triggered fluorescence switching of gold nanoparticles conjugated with Cy3-tagged aptamer.

Gold nanoparticles (AuNPs) conjugated with Cy3-tagged aptamer which can specifically recognize chloramphenicol (CAP) (referred to as AuNPs-AptCAP) are described. CAP can trigger the configuration change of CAP binding aptamer, and thus switching the fluorescence of AuNPs-AptCAP through changing the efficiency of the fluorescence resonance energy transfer (FRET) system with Cy3 as donors and AuNPs as recipients. AuNPs-AptCAP exhibits a linear range of CAP concentrations from 26.0 to 277 µg L-1 with a limit of detection of 8.1 µg L-1 when Cy3 was excited at 530 nm and emission was measured at 570 nm. More importantly, AuNPs-AptCAP can be utilized as signal transducers for the build-up of a series of logic gates including YES, PASS 0, INH, NOT, PASS 1, and NAND. Utilizing the principle of a metal ion-mediated fluorescence switch together with a strong metal ion chelator, the fluorescence of AuNPs-AptCAP could be modulated by adding metal ions and EDTA sequentially. Therefore, a "Plug and Play" logic system based on AuNPs-AptCAP has been realized by simply adding other components to create new logic functions. This work highlights the advantages of simple synthesis and facile fluorescence switching properties, which will provide useful knowledge for the establishment of molecular logic systems. Graphical abstract.

Multilevel, Dual-Readout Logic Operations Based on pH-Responsive Holmium(III)-Doped Carbon Nanodots.

The increasing demand for large-scale integrated logic systems urges the development of multireadout molecular logic gates. Especially, it is of great significance to explore dual-readout logic devices with both fluorescence (FL) and magnetic resonance (MR) signals as measurable outputs, since the signal combination of FL/MR might render molecular logic devices better practicality in biomedical applications. In this study, holmium(III)-doped carbon nanodots (Ho-CDs), which exhibited pH-responsive behaviors in both FL and MR signals, were synthesized by a facile one-pot pyrolysis method. When triggered by H+, Fe3+, or Fe2+, the Ho-CDs served as a switch for both FL and MR signals, leading to dual-readout and multiaddressable logic gates. A series of elementary Boolean operations including YES, NOT, OR, NOR, XOR, PASS 0, and INH have been successfully demonstrated by varying the chemical inputs of H+/Fe3+/Fe2+. More importantly, multilevel integrative Boolean operations with higher functions (NOR-INH and MR (XOR + INH)-OR), which realize the concatenation of different logic gates, have also been successfully demonstrated. This study may pave an avenue to design multilevel, dual-readout molecular logic systems with better operation stability, which hold great potential for biomedical applications in the future.

Iridium(III) and gadolinium(III) loaded and peptide-modified silica nanoparticles for photoluminescence and magnetic resonance (dual) imaging.

The combination of non-invasive fluorescence (FL) and magnetic resonance (MR) imaging can compensate for disadvantages in terms of resolution and sensitivity. However, the preparation of dual-mode probes simultaneously exhibiting strong brightness and high MR response is challenging. A multifunctional nanoprobe was synthesized for targeted photoluminescence (PL) and MR dual-modal imaging. It was obtained by conjugating iridium(III) complexes, gadolinium(III) and the peptide arginine-glycine-aspartate (RGD) onto silica nanoparticles (Ir@SiO2-Gd-RGD NPs). They are highly water soluble, have an average diameter of ~50 nm, and emit strong yellowish green PL (with excitation/emission peaks at 380/572 nm). Simultaneously, the nanoprobes exhibit high MR response with a longitudinal relaxation of 7.16 mM-1 s-1. Instead of simple encapsulation, Ir(III) complexes were covalently conjugated to silica matrix to enhance the chemical and photochemical stability of the nanoprobes. The excellent biocompatibility and PL/MR dual modal imaging capability of the NPs is demonstrated using HeLa cells and mice as models.

[Change of matrix metalloproteinase-1 and matrix metalloproteinase-7 in serum and bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and sarcoidosis].

OBJECTIVE: To detect the levels of matrix metalloprotease (MMP)-1 and MMP-7 in the serum and the bronchoalveolar lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis (IPF) and sarcoidosis (Stage II), and therefore to investigate the significance of these changes in the pathogenesis of IPF. METHODS: Forty-four clinically confirmed cases of IPF were recruited, with the patients' age ranging from 46 to 70 years (58 ± 9 years). Twenty patients with sarcoidosis, aged 35 to 65 (50 ± 12) years, were also studied. Enzyme-linked immunoabsorbent assay was used to detect the levels of MMP-1 and MMP-7 in the serum and the BALF samples. RESULTS: In the serum of patients with IPF, the level of MMP-1 [3.78 (0.14 - 13.44) µg/L] was lower than that in patients with sarcoidosis [7.79 (4.67 - 10.68) µg/L (z = -3.53, P < 0.01)], but the level of MMP-7 [7.83 (3.57 - 14.37) µg/L] was higher than that in patients with sarcoidosis [4.04 (0.06 - 9.94) µg/L (z = -3.84, P < 0.01)]. In the BALF of patients with IPF, the level of MMP-1 [1.09 (0.04 - 5.14) µg/L] was lower than that in patients with sarcoidosis [2.08 (0.05 - 4.16) µg/L (z = -1.53, P > 0.05)], but the level of MMP-7 [3.75 (1.10 - 9.87)µg/L] was higher than that in patients with sarcoidosis [1.16 (0.02 - 4.47) µg/L (z = -5.33, P < 0.01)]. The serum level of MMP-7 in patients with IPF was negatively correlated with the diffusing capacity of carbon monoxide(r = -0.56, P < 0.01) and the percentage of neutrophils (r = -0.47, P < 0.01). The level of MMP-7 in the BALF showed a negative correlation with diffusing capacity of carbon monoxide (r = -0.31, P < 0.05). CONCLUSIONS: The results suggest that MMP-1 may be increased in the inflammatory phase as compared to the matrix remodeling phase of lung fibrosis, while MMP-7 may be increased in the matrix remodeling phase rather than in the inflammatory phase. MMP-7 may act as an important indicator for the severity of IPF.