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To explore the role of bronchoscopy for the assessment of checkpoint inhibitor pneumonitis (CIP), a retrospective single-center study was conducted to assess patients diagnosed with CIP at grade 2 or above and also underwent bronchoscopy between January 2020 and December 2022. Clinical data and bronchoscopic findings were recorded. The treatment data and prognosis information were collected. Twenty-one patients who underwent bronchoscopy and were diagnosed with CIP were enrolled in this study. All patients underwent bronchoalveolar lavage fluid (BALF) analysis. Of them, T lymphocyte subsets of BALF were tested in 15 cases. Transbronchial cryobiopsy (TBCB) was performed in 8 patients, and transbronchial lung biopsy was performed in 5 patients. 3 patients developed pneumothorax after TBCB and all recovered without serious compilations.14 patients experienced grade 2 CIP, while 7 patients ≥ grade 3 CIP. Symptoms were improved in 19 (90.5%) patients after standard treatment adhering to CIP guidelines. However, 5 patients relapsed during steroid tapering. Factors related to the severity and recurrence of CIP were analyzed. Patients with previous interstitial lung disease (ILD) were more likely to develop high grade CIP than those without [83.3% (5/6) versus 15.4% (3/15), P = 0.011].The odds ratio (OR) was 32.5 (95% CI 2.284-443.145, P = 0.009). Increased BALF lymphocyte percentage was associated with high grade CIP, OR 1.095 (95% CI 1.001-1.197, P = 0.047), and higher possibility of CIP relapse, OR 1.123 (95% CI, 1.005-1.225, P = 0.040). Lymphocyte subsets were tested in 15 patients. CD4/CD8 > 1 was found in 80% (4/5) of relapsed patients and 20% (2/10) of patients without relapse (P = 0.047). The OR was 16.00 (95% CI 1.093-234.24, P = 0.043). In this retrospective study, patients with previous ILD was more likely to develop high grade CIP. Higher lymphocyte percentage in BALF was associated with high grade CIP and susceptibility to relapse during treatment of CIP. A CD4/CD8 ratio greater than 1 in lymphocyte subsets of BALF was associated with higher possibility of CIP relapse. We found that TBCB is a safe procedure in CIP patients.
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Líquido del Lavado Bronquioalveolar , Broncoscopía , Inhibidores de Puntos de Control Inmunológico , Neumonía , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Masculino , Femenino , Broncoscopía/métodos , Persona de Mediana Edad , Anciano , Neumonía/inmunología , Neumonía/patología , Neumonía/etiología , Estudios Retrospectivos , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Recurrencia , Índice de Severidad de la Enfermedad , Adulto , Pronóstico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/inmunologíaRESUMEN
Introduction Previous meta-analyses have explored the diagnostic accuracy and safety of computed tomography-guided percutaneous lung biopsy of ground-glass opacities (GGOs). However, no research has investigated the role of nonsurgical biopsies (including transbronchial approaches). Additionally, studies reporting the diagnostic accuracy of GGOs with different characteristics are scarce, with no quantitative assessment published to date. We performed a systematic review to explore the diagnostic accuracy and safety of nonsurgical biopsy for diagnosing GGOs, especially those with higher ground-glass component and smaller nodule sizes. Methods A thorough literature search of four databases was performed to compile studies evaluating both or either of the diagnostic accuracy and complications of nonsurgical biopsy for GGOs. A bivariate random-effects model and random-effect model were utilized for data synthesis. The methodological quality of the studies was assessed according to the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results Nineteen eligible studies with a total of 1,379 biopsy-sampled lesions were analyzed, of which 1,124 were confirmed to be malignant. Nonsurgical biopsy reported a pooled sensitivity of 0.89, a specificity of 0.99, and negative predictive value (NPV) of 60.3%. The overall sensitivity, specificity, and NPV of nonsurgical biopsy for diagnosing GGOs according to GGO component were 0.90, 0.99, and 77.2% in pure GGOs; 0.87, 0.99, and 67.2% in GG-predominant lesions; and 0.89, 1.00 and 44.1% in solid-predominant lesions, respectively. Additionally, the diagnostic sensitivity was better in lesions ≥ 20 mm than in small lesions (0.95 vs 0.88). Factors that contributed to higher sensitivity were the use of coaxial needle system and CT fluoroscopy, but not the needle gauge. The summary sensitivity of core needle biopsy (CNB) was not significantly higher than fine needle aspiration (FNA) (0.92 vs 0.84; P = 0.42); however, we found an increased incidence of hemorrhage in CNB compared with FNA (60.9% vs 14.2%; P = 0.012). Conclusion Nonsurgical biopsy for diagnosing GGOs shows high sensitivity and specificity with an acceptably low risk of complications. However, negative biopsy results are unreliable in excluding malignancy, necessitating resampling or subsequent follow-up. The applicability of our study is limited due to significant heterogeneity, indirect comparisons, and the paucity of data on bronchoscopic approaches, restricting the generalizability of our findings to patients requiring transbronchial biopsies. Trial Registry: PROSPERO; No.: CRD42023429977; URL: www.crd.york.ac.uk/PROSPERO/).
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Background and Aims: Immune checkpoint inhibitors (ICIs) across multiple treatment lines have not yet been evaluated comprehensively. The purpose of this research was to investigate whether or not continuous cross-line ICIs therapy is effective in treating non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective investigation into the medical histories of 47 patients diagnosed with advanced NSCLC and treated with ICIs at the Peking University First Hospital between January 2018 and June 2022. Results: Due to the progression of their disease, 14 patients were given the same ICIs, 5 patients were given different ICIs, and 6 patients discontinued taking ICIs altogether. The objective response rates were 7.140% in the ICIs cross-line treatment group, 0% in the replacement of ICIs treatment group, and 0% in the discontinuation of ICIs treatment group. The disease control rates were 64.260% in the ICIs cross-line treatment group, 60% in the replacement of ICIs treatment group, and 0% in the discontinuation of ICIs treatment group. The average overall survival durations of the three groups were 24.020 (95% confidence interval [CI]: 17.061-30.979), 31.643 (95% CI: 23.513-39.774), and 7.997 (95% CI: 3.746-12.247) months, respectively (p = 0.003). The median second progression-free survival (PFS2) durations of the three groups were 4.570 (95% CI: 3.276-5.864), 3.530 (95% CI: 0.674-6.386), and 1.570 (95% CI: 0-4.091) months, respectively (p = 0.091). Conclusions: Cross-line ICIs cannot improve the prognosis and PFS2 of patients with NSCLC, but compared to discontinuing ICIs, OS may be prolonged. A few patients may benefit from prolonged ICIs therapy.
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The expression of prostate-specific membrane antigen (PSMA) in prostate cancer is 100-1000 times higher than that in normal tissues, and it has shown great advantages in the diagnosis and treatment of prostate cancer. The combination of PSMA and PET imaging technology based on the principle of metabolic imaging can achieve high sensitivity and high specificity for diagnosis. Due to its suitable half-life (109 min) and good positron abundance (97%), as well as its cyclotron accelerated generation, 18F has the potential to be commercialize, which has attracted much attention. In this article, we synthesized a series of fluorosulfate PET tracers targeting PSMA. All four analogues have shown high affinity to PSMA (IC50 = 1.85-5.15 nM). After the radioisotope exchange labeling, [18F]L9 and [18F]L10 have PSMA specific cellular uptake (0.65 ± 0.04% AD and 1.19 ± 0.03% AD) and effectively accumulated in 22Rv1 xenograft mice model. This study demonstrates that PSMA-1007-based PSMA-targeted aryl [18F]fluorosulfate novel tracers have the potential for PET imaging in tumor tissues.
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Antígenos de Superficie , Diseño de Fármacos , Radioisótopos de Flúor , Tomografía de Emisión de Positrones , Radiofármacos , Animales , Humanos , Masculino , Radioisótopos de Flúor/química , Ratones , Antígenos de Superficie/metabolismo , Radiofármacos/síntesis química , Radiofármacos/química , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismo , Glutamato Carboxipeptidasa II/metabolismo , Estructura Molecular , Línea Celular Tumoral , Neoplasias Experimentales/diagnóstico por imagen , Neoplasias Experimentales/metabolismo , Relación Estructura-ActividadRESUMEN
BACKGROUND: Photodynamic therapy (PDT) is a promising interventional treatment approach that contributes to antitumor immunity. It has been reported that PDT can enhance the effectiveness of immune checkpoint inhibitors (ICIs), but its mechanism is yet unclear. Herein, we implemented bioinformatics analysis to detect common pathways and potential biomarkers in non-small cell lung cancer (NSCLC), PDT, and NSCLC immunotherapy to investigate potential links between PDT, immunotherapy and NSCLC, and their clinical impact. METHODS: Differentially expressed genes in NSCLC- and NSCLC immunotherapy-related data in the GEO database were intersected with PDT-related genes in the GeneCards database to obtain candidate genes and shared pathways. Enrichment analysis and protein-protein interaction were established to identify key genes in functionally enriched pathways. The expression profiles and the prognostic significance of key genes were depicted. RESULTS: Bioinformatics analysis showed that HIF-1α was screened as a prognostic gene in hypoxia, HIF-1, and PD-L1-related signaling pathways, which was associated with clinical response in NSCLC patients after PDT and immunotherapy. In vivo experiments showed that PDT could inhibit tumor growth and upregulate HIF-1α and PD-L1 expressions in NSCLC tissues with a positive correlation, which might influence the blocking activity of ICIs on the HIF-1, and PD-L1-related signaling pathways. CONCLUSIONS: PDT might improve the clinical response of ICIs by upregulating tumor HIF-1α and PD-L1 expressions in NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Fotoquimioterapia , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Relevancia Clínica , Antígeno B7-H1/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genéticaRESUMEN
Background: Consumer wearable devices such as wristbands and smartwatches have potential application value in communicable disease surveillance. Objective: We investigated the ability of wearable devices to monitor COVID-19 patients of varying severity. Methods: COVID-19 patients with mobile phones supporting wearable device applications were selected from Dalian Sixth People Hospital. Physiological parameters from the wearable devices and electronic questionnaires were collected from the device wearing until 14 days post-discharge. Clinical information during hospitalization was also recorded. Based on imaging data, the patients were categorized into the milder group without pneumonia and the more severe group with pneumonia. We plotted the curves of the physiological parameters of the two groups to compare the differences and changes. Results: Ninety-eight patients were included in the analysis. The mean age was 39.6 ± 10.5 years, including 45 males (45.9%). There were 24 asymptomatic patients, 10 mild patients, 60 moderate patients, and 4 severe patients. Compared with the milder group, the more severe group had higher heart rate-related parameters, while the heart rate variability (HRV) was the opposite. In the more severe group, the heart rate-related parameters showed a downward trend from 0 to 7 days after the fever resolution. Among them, the resting heart rate and sleep heart rate decreased on the 25th day after the onset and were close to the milder group 1 week after discharge. Conclusions: Consumer wearable devices have the potential to monitor respiratory infections. Heart rate-related parameters obtained from these devices can be sensitive indicators of COVID-19 severity and correlate with disease evolution. Trial registration: ClinicalTrials.gov NCT04459637.
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BACKGROUND: No studies have investigated whether high-sensitivity C reactive protein (hsCRP) can be used to predict the forced expiratory volume in 1 s (FEV1)/estimated value of FEV1 (FEV1%pred). This study aimed to assess the association between hsCRP and FEV1%pred in middle-aged and elderly individuals without underlying lung disease. METHODS: The data for this study were obtained from a prospective cohort study that included 1047 middle-aged and elderly citizens from Beijing aged 40-75 years without any evidence of underlying lung diseases with FEV1 >70% after receiving inhalational bronchodilators. The baseline analysis of the participants was performed from 30 May 2018 to 31 October 2018. Restricted cubic spline regression and multivariate linear regression models were used to assess the non-linear association and linear association between hsCRP and FEV1/FEV in 6 s (FEV6) and FEV1%pred, respectively. RESULTS: The hsCRP values of 851 participants were recorded; the values were normal in 713 (83.8%) participants. The remaining 196 participants (18.7%) had missing data. A non-linear association was observed between normal hsCRP values and FEV1/FEV6. hsCRP was linearly and negatively correlated with FEV1%pred, and each 1 SD increase in hsCRP was significantly associated with a 2.4% lower in FEV1%pred. Significantly higher FEV1/FEV6 differences were observed in the female subgroup than those in the male subgroup (p=0.011 for interaction). CONCLUSIONS: hsCRP had a non-linear association with FEV1/FEV6 and a linear negative association with FEV1%pred in individuals with normal hsCRP values. hsCRP can be used to predict FEV1%pred, which can be used to predict the development of chronic obstructive pulmonary disease. hsCRP has a stronger association with lung function in women than that in men. TRIAL REGISTRATION NUMBER: NCT03532893.
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Enfermedades Pulmonares , Pulmón , Anciano , Persona de Mediana Edad , Humanos , Masculino , Femenino , Volumen Espiratorio Forzado , Beijing/epidemiología , Estudios Prospectivos , Proteína C-ReactivaRESUMEN
BACKGROUND: Photodynamic therapy (PDT) is a relatively safe and highly selectivity antitumor treatment, which might be increasingly used as a supplement to conventional therapies. A clinical overview and detailed comparison of how to select patients and lesions for PDT in different scenarios are urgently needed to provide a basis for clinical treatment. SUMMARY: This review demonstrates the highlights and obstacles of applying PDT for lung cancer and underlines points worth considering when planning to initiate PDT. The aim was to make out the appropriate selection and help PDT develop efficacy and precision through a better understanding of its clinical use. KEY MESSAGES: Increasing evidence supports the feasibility and safety of PDT in the treatment of non-small cell lung cancer. It is important to recognize the factors that influence the efficacy of PDT to develop individualized management strategies and implement well-designed procedures. These important issues should be worth considering in the present and further research.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Fotoquimioterapia , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Fotoquimioterapia/métodosRESUMEN
Immune inflammation has long been implicated in the pathogenesis of schizophrenia. Despite as a rapid and effective physical therapy, the role of immune inflammation in electroconvulsive therapy (ECT) for schizophrenia remains elusive. The neutrophils to lymphocytes (NLR), platelets to monocytes (PLR) and monocytes to lymphocytes (MLR) are inexpensive and accessible biomarkers of systemic inflammation. In this study, 70 schizophrenia patients and 70 age- and sex-matched healthy controls were recruited. The systemic inflammatory biomarkers were measured before and after ECT. Our results indicated schizophrenia had significantly higher peripheral NLR, PLR and MLR compared to health controls at baseline, while lymphocytes did not differ. After 6 ECT, the psychiatric symptoms were significantly improved, as demonstrated by the Positive and Negative Syndrome Scale (PANSS). However, there was a decline in cognitive function scores, as indicated by the Mini-Mental State Examination (MMSE). Notably, the neutrophils and NLR were significantly reduced following ECT. Although lymphocytes remained unchanged following ECT, responders had significantly higher lymphocytes compared to non-responders. Moreover, the linear regression analyses revealed that higher lymphocytes served as a predictor of larger improvement in positive symptom following ECT. Overall, our findings further highlighted the presence of systemic inflammation in schizophrenia patients, and that ECT may exert a therapeutic effect in part by attenuating systemic inflammation. Further research may therefore lead to new treatment strategies for schizophrenia targeting the immune system.
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Terapia Electroconvulsiva , Esquizofrenia , Humanos , Esquizofrenia/terapia , Terapia Electroconvulsiva/métodos , Resultado del Tratamiento , Biomarcadores , Inflamación/terapiaRESUMEN
OBJECTIVES: Morning dry mouth, commonly seen in Obstructive Sleep Apnea (OSA) patients, is absent in current OSA screening tools. This study evaluated the link between morning dry mouth and OSA's clinical symptoms and complications, aiming to determine its viability as a screening indicator. METHODS: This research analyses baseline data from a prospective cohort study (the PIFCOPD study). Demographic information, medical history, and the presence of morning dry mouth symptoms were collected. The STOP-Bang questionnaire was performed for OSA screening. Logistic regression analyses were employed to establish the correlations between morning dry mouth and the clinical symptoms and comorbidities of OSA. RESULT: 1291 participants (62.1±7.5 years; 501 males, 790 females) were included, of which 416 reported morning dry mouth (32.2%). 42.6% in the high-risk OSA group and 22.1% in the low-risk group reported morning dry mouth. Individuals with morning dry mouth also showed higher STOP-Bang scores (3.3±1.6 vs. 2.3±1.4, P<0.01). Significant associations were found between morning dry mouth and loud snoring, observed sleep apnea, daytime fatigue, and hyperlipidemia (P<0.01), but not with alcohol consumption, tea consumption, diabetes, or hypertension. CONCLUSION: Morning dry mouth is associated with increased OSA risk and its clinical signs, suggesting its potential as an OSA screening symptom. CLINICAL TRIAL REGISTRATION: This study has been registered at www.ClinicalTrials.gov (registration identifier: NCT03532893) on 21 May 2018.
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Apnea Obstructiva del Sueño , Xerostomía , Masculino , Femenino , Humanos , Estudios Transversales , Estudios Prospectivos , Comorbilidad , Encuestas y Cuestionarios , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/complicaciones , Xerostomía/epidemiología , Xerostomía/complicaciones , Tamizaje MasivoRESUMEN
BACKGROUND AND OBJECTIVE: To clarify the prevalence, features and outcomes of small airway disease (SAD) in a Chinese cohort with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) related pulmonary involvement. METHODS: SAD was recorded when the manifestations of either centrilobular nodules or air trapping were observed according to CT scans, except for infection or other airway-related comorbidities. Baseline and follow-up data were collected retrospectively. RESULTS: Of the 359 newly diagnosed AAV patients with pulmonary involvement, 92 (25.6%) had SAD, including 79 (85.9%) cases of anti-MPO-ANCA positive, 9 (9.8%) cases of anti-PR3-ANCA positive and 2 (2.2%) cases of double positive. Patients with SAD were more likely to be younger, female, non-smokers, have more ear-nose-throat (ENT) involvement, and have higher baseline Birmingham Vasculitis Activity Score (BVAS) compared to patients without SAD. Several AAV-related SAD patients have improved lung function and CT scans after immunosuppressive therapy. Patients with SAD had a better prognosis compared to those without SAD. When dividing all patients into three groups: isolated SAD (only small airway involvements), SAD with other lower airway involvements, and non-SAD, patients in the SAD with other lower airway involvements group had the highest risk of infection, while patients in the non-SAD group had the worst long-term outcomes. Similar results were observed in anti-MPO-ANCA positive patients when performing subgroup analyses. CONCLUSION: SAD is a unique manifestation of AAV-related lung involvement and exhibits distinct clinical features. It is vital to focus on SAD because of its association with prognosis and infection in AAV patients, especially in anti-MPO-ANCA positive patients. Moreover, SAD might represent a better response to immunosuppressors.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Anticuerpos Anticitoplasma de Neutrófilos , Humanos , Femenino , Estudios Retrospectivos , Mieloblastina , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Pronóstico , PeroxidasaRESUMEN
OBJECTIVE: The objective of this study is to study the adjunct role of combining DNA aneuploidy analysis with radial endobronchial ultrasound (R-EBUS)-guided sampling for diagnosis of peripheral lung lesions (PPLs). METHOD: A single-center prospective study was conducted in patients undergoing R-EBUS-guided sampling for PPLs. DNA image cytometry (DNA-ICM) was used to analyze DNA aneuploidy in bronchial washing from the bronchial segment of the PPL. Clinical information, R-EBUS data, pathology, DNA-ICM results, and follow-up data were analyzed. Sensitivity, specificity, and predictive values for R-EBUS-guided sampling, DNA-ICM, and the two methods combined were measured. Binary logistic regression was performed to determine influencing factors on diagnostic positivity rate. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff point for DNA-ICM. RESULTS: A total of 101 patients were enrolled. Sixty-four (63.4%) patients had confirmed malignant tumor, of whom 33 were confirmed by R-EBUS-guided sampling (biopsy and/or bronchial brush and wash cytology), and 31 by surgery or percutaneous lung biopsy. Thirty-seven patients were finally considered to have benign lesions, based on clinical information and 1-year follow-up. The sensitivity for malignant disease was 51.6% by R-EBUS, and specificity was 100%. DNA-ICM had a sensitivity of 67.2% and a specificity of 86.5%. When combining the two methods, sensitivity increased to 78.1% and specificity was 86.5%. Lesion size and whether the R-EBUS probe was located in the lesion were significantly associated with positivity rate of the combined methods. The optimal cutoff point for DNA-ICM was 5c for max DNA content, and 1 for aneuploid cell count (sensitivity 67.2%, specificity 86.5%, accuracy 63.4%). CONCLUSION: In malignant PPLs, DNA-ICM combined with R-EBUS-guided sampling can improve diagnostic positivity compared with either method alone.
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Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/genética , Estudios Prospectivos , Broncoscopía/métodos , Bronquios/diagnóstico por imagen , Bronquios/patología , Endosonografía/métodos , Ultrasonografía Intervencional/métodos , Aneuploidia , Citometría de Imagen , Estudios RetrospectivosRESUMEN
OBJECTIVE: Treatment options for acquired tracheal stenosis (ATS) are limited due to a series of pathophysiological changes including inflammation and cell proliferation. Micro ribonucleic acid-21-5p (miR-21-5p) may promote the excessive proliferation of fibroblasts. However, various types of fibrosis can be prevented with pirfenidone (PFD). Currently, the effect of PFD on miR-21-5p and its biological function has not been clarified. In this study, PFD was evaluated as a potential treatment for ATS by inducing fibroblast proliferation in lipopolysaccharide (LPS)-induced fibroblasts by targeting miR-21-5p. METHODS: For 48 h, 1 g/ml LPS was used to generate fibroblasts in vitro, followed by the separation of cells into four groups: control, PFD, mimic, and mimic + PFD. The Cell Counting Kit-8 (CCK-8) technique was adopted to measure the proliferation of fibroblasts. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB) were used to measure the relative expressions of tumor necrosis factor-α (TNF-α), transforming growth factor-ß1 (TGF-ß1), drosophila mothers against decapentaplegic 7 (Smad7) and collagen type I alpha 1(COL1A1) messenger RNA (mRNA) and proteins, respectively. RESULTS: (1) At 0, 24, 48, and 72 h, fibroblast growth was assessed using the CCK-8 method. Compared with the control group, the mimic group showed the highest fibroblast viability, and the PFD group showed the lowest fibroblast viability. However, fibroblast viability increased in the mimic + PFD group but decreased in the mimic one. (2) RT-qPCR and WB showed that the mimic group exhibited a significant up-regulation in the relative expressions of TNF-α, TGF-ß1, and COL1A1 mRNA and proteins but a down-regulation in the relative expression of Smad7 mRNA and protein compared with the control one. In the PFD group, the results were the opposite. Nevertheless, the relative expressions of TNF-α, TGF-ß1, and COL1A1 mRNA and proteins were increased, whereas that of Smad7 mRNA was decreased in the mimic + PFD group. The change was less in the mimic group. CONCLUSION: PFD may have a preventive and curative effect on ATS by inhibiting fibroblast proliferation and the fibrotic process and possibly through down-regulating miR-21-5p and up-regulating Smad7 and its mediated fibrotic and inflammatory responses.
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MicroARNs , Piridonas , Estenosis Traqueal , Humanos , Regulación hacia Abajo , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/farmacología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Estenosis Traqueal/tratamiento farmacológico , Estenosis Traqueal/etiología , Lipopolisacáridos/metabolismo , Lipopolisacáridos/farmacología , Fibroblastos/metabolismo , Fibroblastos/patología , MicroARNs/genética , Fibrosis , Proliferación Celular , ARN MensajeroRESUMEN
BACKGROUND: Morning dry mouth (MDM) is a common symptom of Obstructive Sleep Apnea (OSA) yet current OSA screening tools overlook it. OBJECTIVE: To enhance the specificity of the Stop-Bang questionnaire (SBQ) by adding an MDM symptom. METHOD: A retrospective analysis on 590 patients from Peking University First Hospital (2013-2018) suspected of OSA was conducted. They underwent polysomnography. The research incorporated the MDM symptom into SBQ and adjusted the body mass index (BMI) threshold to 28 kg/m2. Predictive parameters were then calculated. RESULTS: 83.1% patients were diagnosed with OSA, with 61.4% reporting MDM. Multivariate regression confirmed MDM significantly influenced Apnea-Hypopnea Index (AHI). Adjusted SBQ with MDM showed a slight decrease in sensitivity but improved specificity, especially when using a BMI threshold of > 28 kg/m2. For AHI ≥ 5 events/h and AHI ≥ 15 events/h, adjusted SBQ with MDM (BMI >28 kg/m2) obtained the highest Youden index. CONCLUSION: Incorporating the MDM symptom into SBQ and adjusting the BMI threshold enhances the diagnostic specificity for OSA.
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Apnea Obstructiva del Sueño , Xerostomía , Humanos , Índice de Masa Corporal , Estudios Retrospectivos , China , Apnea Obstructiva del Sueño/diagnóstico , Encuestas y CuestionariosRESUMEN
BACKGROUND: Photodynamic therapy (PDT) is receiving increasing attention in treating non-small cell lung cancer (NSCLC) worldwide, but in clinical practice, the relationship between treatment effect and PDT light dose in NSCLC remains unclear. Therefore, we aimed to determine the optimal light dose for PDT by exploring molecular biomarkers and evaluating tumor growth data. METHODS: We applied bioinformatics to identify promising genes and pathways in NSCLC and PDT. Then, the human lung adenocarcinoma cell line A549-bearing BALB/c nude mice were treated with hematoporphyrin derivative (HPD, 3 mg/kg) that is currently used widely for lung cancer treatment in the world even with photosensitization issues. After 48 h, tumor-bearing mice were irradiated superficially at doses of 100, 200, 300, 400, and 500 J/cm2. The tumor growth data and apoptotic molecules were assessed and calculated. RESULTS: Bioinformatics results indicated that the apoptosis pathway was significantly enriched and caspase 3 was the most promising biomarker on prognosis in NSCLC-PDT. Compared to the untreated group, there was no difference in the relative tumor volume (RTV) of the 100 J/cm2 group, while the RTV of the other treatment groups (200-500 J/cm2) was significantly lower. In the 100 J/cm2 group, there were significant differences in the complete remission (CR, 0 %) and the percentage of tumor growth inhibition rate (TGI%) over 75 % (20 %) compared with the other treatment groups, especially the 300 and 400 J/cm2 groups (CR 70 %; TGI% 90 %). In the 300 and 400 J/cm2 groups, the expression of caspase 3, cleaved-caspase 3, PARP1, and Bax was increased significantly, while Bcl-2 expression was significantly lower. CONCLUSIONS: Moderate doses of PDT (300 or 400 J/cm2) are more effective than low (100 or 200 J/cm2) or high doses (500 J/cm2) in the A549 tumor-bearing mice model. Since the A549 tumor is more akin to human tumors in pathological behavior, these experimental data may contribute to improving HPD-PDT illumination protocols for favorable clinical outcomes.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Fotoquimioterapia , Humanos , Animales , Ratones , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Ratones Desnudos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Caspasa 3 , Fotoquimioterapia/métodos , Derivado de la Hematoporfirina/farmacología , Derivado de la Hematoporfirina/uso terapéutico , Modelos Animales de Enfermedad , Línea Celular Tumoral , ApoptosisRESUMEN
Pandemic of COVID-19 hit China at the end of 2022. According to China Center for Disease Control and Prevention, Omicron BA.5.2 and BF.7 were the main circulating variants. Chinese people had a high COVID-19 vaccination rate, and the most widely used vaccines were CoronaVac (Sinovac) and BBIBP-CorV (Sinopharm). An online questionnaire was distributed to survey the vaccination history and infection information of China mainland residents during this pandemic. A total of 4250 subjects were included for propensity score matching, 566 unvaccinated subjects and 1072 vaccinated subjects were finally included to analyze the effects of the two vaccines on BA.5.2 and BF.7. The SARS-CoV-2 infection rate was 84.5% in the vaccinated group and 82.3% in the unvaccinated group (p = 0.255). Vaccinated subjects had significantly higher rates of COVID-19-related symptoms, including fever, cough, nasal obstruction, runny nose, and sore throat. However, vaccinated people had lower risk of pneumonia (odds ratio [OR]: 0.467, 95% confidence interval [CI]: 0.286-0.762) and hospitalization (OR: 0.290, 95% CI: 0.097-0.870) due to COVID-19. In general, the current study did not observe the protective effect of CoronaVac and BBIBP CorV against BA.5.2 and BF.7 infection. However, these vaccines can still reduce the risk of adverse outcomes such as pneumonia and hospitalization.
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COVID-19 , Vacunas , Humanos , SARS-CoV-2 , Vacunas contra la COVID-19 , COVID-19/epidemiología , COVID-19/prevención & control , Estudios Retrospectivos , China/epidemiologíaRESUMEN
Pigeon paramyxovirus 1 (PPMV-1) is an antigenic host variant of avian paramyxovirus 1. Sporadic outbreaks of PPMV-1 infection have occurred in pigeons in China; however, few cases of human PPMV-1 infection have been reported. The purpose of this article is to report a case of severe human PPMV-1 infection in an individual with probable post-COVID-19 syndrome (long COVID) who presented with rapidly progressing pulmonary infection. The patient was a 66-year-old man who was admitted to the intensive care unit 11 days after onset of pneumonia and recovered 64 days after onset. PPMV-1 was isolated from the patient's sputum and in cloacal smear samples from domesticated pigeons belonging to the patient's neighbour. Residual severe acute respiratory syndrome coronavirus 2 was detected in respiratory and anal swab samples from the patient. Sequencing analyses revealed that the PPMV-1 genome belonged to genotype VI.2.1.1.2.2 and had the 112RRQKRF117 motif in the cleavage site of the fusion protein, which is indicative of high virulence. This case of cross-species transmission of PPMV-1 from a pigeon to a human highlights the risk of severe PPMV-1 infection in immunocompromised patients, especially those with long COVID. Enhanced surveillance for increased risk of severe viral infection is warranted in this population.
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COVID-19 , Masculino , Animales , Humanos , Anciano , Columbidae , Virus de la Enfermedad de Newcastle/genética , Síndrome Post Agudo de COVID-19 , Variación AntigénicaRESUMEN
The kynurenine pathway (KP) of tryptophan has been implicated in the pathogenesis of schizophrenia and its interaction with the immune system has been suggested to play a role. In this study, 28 schizophrenia patients and 25 healthy controls were recruited and divided into different inflammatory subgroups using a two-step recursive clustering analysis. Cytokine gene expression and plasma KP metabolites were measured before, during and after treatment. Our findings indicated that schizophrenia patients had lower levels of Tryptophan (TRP), N-formylkynurenine (NFK), xanthinic acid (XA), quinolinic acid (QA), kynurenic acid (KYNA), KYNA/KYN and QA/KYNA, but higher levels of IL-18 mRNA, KYN/TRP compared to healthy controls (all p < 0.05). After electroconvulsive therapy (ECT), patients with low inflammation achieved better clinical improvement (PANSS scores) compared to those with high inflammation (F = 5.672, P = 0.025), especially in negative symptoms (F = 6.382, P = 0.018, η2 = 0.197). While IL-18 mRNA (F = 32.910, P < 0.0001) was significantly decreased following ECT, the KYN/TRP (F = 3.455, p = 0.047) and KYNA/TRP (F = 4.264, P = 0.026) only significantly decreased in patients with low inflammation. Correlation analyses revealed that baseline IL-18 gene expression significantly correlated with pre- (r = 0.537, p = 0.008) and post-KYNA/TRP (r = 0.443, p = 0.034), post-KYN/TRP (r = 0.510, p = 0.013), and post-negative symptoms (r = 0.525, p = 0.010). Moreover, baseline TRP (r = -0.438, p = 0.037) and XA (r = -0.516, p = 0.012) were negatively correlated with baseline PANSS, while post-KYN (r = -0.475, p = 0.022), 2-AA (r = -0.447, p = 0.032) and KYN/TRP (r = -0.566, p = 0.005) were negatively correlated with Montreal Cognitive Assessment (MoCA) following ECT. Overall, these findings suggested that the association between inflammation and kynurenine pathway plays an essential role in mechanism of ECT for schizophrenia and that the regulation of ECT on KP is influenced by inflammatory characteristics, which may relate to clinical efficacy in schizophrenia.
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Terapia Electroconvulsiva , Esquizofrenia , Humanos , Quinurenina/metabolismo , Triptófano/metabolismo , Interleucina-18 , Esquizofrenia/terapia , Resultado del Tratamiento , Ácido Quinurénico , ARN MensajeroRESUMEN
Acute kidney injury (AKI) is a common clinical syndrome lacking effective pharmacotherapy. Gambogic acid (GA), as an active ingredient of herbal medicines, exhibits antioxidant and anti-inflammatory effects that benefit the treatment of AKI, but its poor aqueous solubility limits effective renal delivery. We, for the first time, developed GA-based nanoparticles (GA-NPs) with preferential renal uptake for AKI treatment. By PEGylating with NH2-PEG5000-NOTA, hydrophobic GA was self-assembled into â¼4.5 nm nanoparticles, which showed the enhanced renal accumulation in AKI models from PET images. Importantly, the in vitro cell assays and in vivo tests of the two AKI models have confirmed the obvious nephroprotective effects and biosafety of GA-NPs. Therefore, this work indicates that GA-NPs can be a promising therapeutic candidate for the management of AKI.