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BACKGROUND: High-flow nasal cannula (HFNC) oxygen therapy is essentially a constant-flow, noninvasive respiratory support system similar to a noninvasive ventilator operating in constant-flow mode. The clinical outcome of HFNC oxygen therapy is strongly associated with the pressure generated by high-flow gas and the patient's comfort level. This study was performed to explore the relevant factors affecting pressure and comfort of HFNC oxygen therapy in vivo. METHODS: Thirty-five healthy volunteers were enrolled in the trial. They underwent placement of nasal cannulas of various inner diameters (3, 4 or 5 mm) and treatment with different HFNC devices [HFT-300 (Weishengkang Medical Technology Co., Ltd., Jiangsu China) or H-80 M (BMC Medical Co., Ltd., Beijing China)],and the nasal airway pressure and comfort were assessed. Multiple linear regression was used to determine predictors of airway pressure. RESULTS: Multiple linear regression showed that the end-expiratory pressure was associated with the flow rate, sex, height, and cannula size. The end-expiratory pressure increased by 0.6 cmH2O per 1-mm increase in cannula diameter, decreased by 0.3 cmH2O per 10-cm increase in participant height (with a 0.35 cmH2O decrease for men), and increased by 1 cmH2O when the flow rate increased by 10 L/min (R2 = 0.75, P < 0.05 for all variables in model). In addition, the pressure generated by the H-80 M device was higher than that generated by the HFT-300 device (P < 0.05). Discomfort manifested as difficulty in expiration, and its severity increased as the cannula diameter increased; however there was no significant difference in comfort between the two HFNC devices (P > 0.05). CONCLUSION: In volunteers undergoing HFNC oxygen therapy, the nasal cannula diameter, flow rate, sex, height, and device model can affect the nasal airway pressure, and the nasal catheter diameter and flow rate can affect comfort. These factors should be given close attention in clinical practice. TRIAL REGISTRATION: ChiCTR2300068313 (date of first registration: 14 February 2023,  https://www.chictr.org.cn ).

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The setting and adjustment of ventilator parameters need to rely on a large amount of clinical data and rich experience. This paper explored the problem of difficult decision-making of ventilator parameters due to the time-varying and sudden changes of clinical patient's state, and proposed an expert knowledge-based strategies for ventilator parameter setting and stepless adaptive adjustment based on fuzzy control rule and neural network. Based on the method and the real-time physiological state of clinical patients, we generated a mechanical ventilation decision-making solution set with continuity and smoothness, and automatically provided explicit parameter adjustment suggestions to medical personnel. This method can solve the problems of low control precision and poor dynamic quality of the ventilator's stepwise adjustment, handle multi-input control decision problems more rationally, and improve ventilation comfort for patients.

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Airborne particle pollution causes a range of respiratory and cardiovascular disorders by entering the human respiratory system through the breathing process. The administration of pharmaceutical particles by inhalation is another effective way to treat pulmonary illnesses. Studying particle deposition in the respiratory system during human breathing is crucial to maintaining human health. This necessity served as the impetus for this work, which aims to investigate how the airflow and particles' deposition are influenced by constant inhalation and circulatory breathing, particle diameter, and changes in airflow rate. The focus of this paper is to compare the particle deposition results of circulatory respiration with constant respiration. Based on computed tomography (CT) scan pictures, a precise human airway model from the mouth cavity to the fifth-generation bronchi was created. Flow fields and particle deposition inside the respiratory tract were examined at varied breathing rates (30, 60, and 90 L/min of constant and circulatory breathing) and varying haled particle sizes (5 and 10 µm). The results showed that the oropharyngeal area is often where the majority of particles are deposited. The particle distribution fraction is more significant in the bronchial area than the oropharyngeal region due to lower inhalation velocities and smaller particle sizes. For particles with a diameter of 5 µm, constant respiration and circulatory respiration have virtually identical particle distribution fractions in each region. For particles with a diameter of 10 µm, the particle distribution fraction for circulatory respiration is slightly higher than for constant respiration in the bronchial region as the flow rate increases. For both constant and circulatory respiration, particles are deposited more in the right lung and less in the left. These results contribute to further research on respiratory diseases caused by inhaled particles and guide inhalation therapy for better treatment outcomes.

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In this report, we describe a 42-year-old man with dyspnea and recurrent hemoptysis who was diagnosed with cardiac angiosarcoma and multiple pulmonary metastases. Before visiting our hospital, he had been misdiagnosed with a lung infection. Bronchoscopy, multiple imaging methods, and extensive laboratory studies failed to identify a clear etiology. Cardiac magnetic resonance imaging and percutaneous lung biopsy revealed cardiac angiosarcoma with multiple pulmonary metastases. Cardiac angiosarcoma is extremely rare and diagnosis is difficult. Diffuse alveolar hemorrhage is not a common manifestation of pulmonary metastases of angiosarcoma and in patients with hemoptysis, clinicians should consider a malignant etiology that is not restricted to the lungs.

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BACKGROUND: Exercise intolerance is among the most common symptoms experienced by patients with chronic obstructive pulmonary disease (COPD), which is associated with lung dynamic hyperinflation (DH). There was evidence that positive expiratory pressure (PEP), which could be offered by less costly devices, could reduce DH. The purpose of this study was to evaluate the efficacy and safety of long-term domiciliary use of PEP device in subjects with COPD. METHODS: A randomized controlled trial was conducted and 25 Pre-COPD or mild-to-very severe subjects with COPD were randomized to intervention group (PEP device, PEP = 5 cmH2O, n = 13) and control group (Sham-PEP device, PEP = 0 cmH2O, n = 12). PEP device was a spring-loaded resistor face mask. Subjects were treated 4 h per day for a total of 2 months. Six-minute walk test (6MWT), pulmonary function, the Modified British Medical Research Council score, and partial pressure of end-tidal carbon dioxide were evaluated at baseline and after two months. RESULTS: The 6MWD (- 71.67 ± 8.70 m, P < 0.001), end-dyspnea (P = 0.002), and end-fatigue (P = 0.022) improved significantly in the intervention group when compared with the control group. All subjects in the intervention group reported that 4 h of daily use of the PEP device was well tolerated and accepted and there were no adverse events. CONCLUSION: Regular daily use of PEP device is safe and may improve exercise capacity in subjects with COPD or pre-COPD. PEP device could be used as an add-on to pulmonary rehabilitation programs due to its efficacy, safety, and low cost. TRIAL REGISTRATION: The study was prospectively registered on ClinicalTrials.gov (NCT04742114).

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PURPOSE: Heated humidified high-flow nasal cannula (HFNC) oxygen therapy is one of the most important oxygen therapy methods, which are commonly applied to relieve dyspnea in advanced cancer patients. Our study aims to observe the efficacy and safety of HFNC oxygen therapy on dyspnea patients with advanced cancer and explore the clinical application. METHODS: Sixty subjects with advanced cancer requiring oxygen therapy from a grade 3, class A hospital in China were recruited and randomized (1:1) to traditional nasal catheter oxygen therapy or HFNC. Primary outcomes were dyspnea, oral dryness, and sleep condition, which were recorded after 72-h treatment. Secondary outcomes were heart rate (HR), respiration rate (RR), SpO2, PaO2, and PaCO2, which were recorded after 2, 6, 24, and 72 h treatment. RESULTS: Seventy-two hours after treatment, there were significant improvements in all primary outcomes (P < 0.001). PaO2 and RR were statistically changed 2 h after HFNC treatment (P < 0.001). PaCO2 and HR were statistically changed 24 h after HFNC treatment (P < 0.001). CONCLUSION: HFNC oxygen therapy has good effect, high safety, and is easy to be accepted by dyspnea patients with advanced cancer. It can be used as the first choice of oxygen therapy for these patients and has broad clinical prospects. TRIAL REGISTRATION: This work was retrospectively registered in the Chinese Clinical Trials Registry (ChiCTR2100049582) on August 4, 2021.

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INTRODUCTION: Abnormal triggering of non-invasive ventilator (NIV) is the main reason for increasing the possibility of patient intolerance and directly affecting the treatment effect. OBJECTIVE: To investigate factors that affect abnormal triggering of NIV. METHODS: Thirty health volunteers from August 2018 to August 2019 were recruited. Two kinds of NIVs, Curative Flexo ST30 and Resmed Stellar™ 150, were selected, with S/T mode, respiratory rate of 10 bpm and inspiration time of 1.0 s. Every volunteer received ventilation in two ventilators, five oxygen flows (5/10/15/20/25 L/min), five support pressures (independent inspired positive airway pressure/expired positive airway pressure [IPAP/EPAP]: 8/4; 10/4; 12/4; 16/6; 20/8 cm H2 O), two oxygen injection sites (proximal to the mask or the ventilator) and three masks (Curative: Bestfit™; Resmed: Mirage Quattro Full Face Mask™; Zhongshan: ZS-MZ-A™) for 60 min, respectively. RESULTS: All factors mentioned above affected normal triggering. With the increase of oxygen flow and support pressure, the frequency of auto-triggering and ineffective-triggering increased (P < 0.05). For Curative Flexo ST30 ventilator, when the oxygen injection site was proximal to the ventilator, the frequency of auto-triggering and ineffective-triggering is significantly lower than when it was proximal to the mask, whereas the result in Resmed Stellar™ 150 is totally different (P < 0.05). CONCLUSION: When using Curative Flexo ST30 ventilator, the oxygen injection site should be proximal to the ventilator, whereas Resmed Stellar™ 150 ventilator is just the opposite. Attention should be paid to the effectiveness of ventilators when oxygen flow and support pressure settings are high, as abnormal triggers occur more frequently. Choosing the suitable mask is also important.

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BACKGROUND: From the point of view of machine construction and hydrodynamics, this paper innovatively proposes that the essence of high-flow nasal cannula (HFNC) is a constant-flow mode in noninvasive ventilator (NIVCFM). This study enrolled healthy adults as study subjects to assess the subjective comfort assessed by visual analog scoring scale of NIVCFM/HFNC and objective comfort measured by the noise level generated by NIVCFM/HFNC, aiming to provide a scientific basis for the rational clinical application of NIVCFM/HFNC. METHODS: Forty-four healthy adults participated in this study. The noise generated by NIVCFM/HFNC is measured, and the comfort is evaluated during NIVCFM delivery at flow rates of 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, and 60 L/min. RESULTS: When the ventilator flow rate is 60 L/min, the maximum noise is 65.9 dB, increasing noise by 23.7 dB from a baseline of 42.2 dB at the flow rate of 0 L/min. There was a strong nonlinear positive correlation between the noise level and the flow rates. The median score for dry mouth, nose or throat, dysphagia, sore throat, and other discomfort was 0. The median score for dyspnea was 0 at 0-30 L/min, 1 at 35-55 L/min, and 2 at 60 L/min. CONCLUSIONS: The grater the flow rate, the greater the noise generated by NIVCFM/HFNC (<65.9 dB). The maximum flow rate that most healthy adults can able to tolerate is 30 L/min, and the main discomfort is dyspnea.

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BACKGROUND: Pseudomonas fluorescens (P. fluorescens) has been detected in respiratory samples from patients. However, no previous reports have been published about these P. fluorescens cultures from lung tissues. CASE PRESENTATION: Here, we report a case of pneumonia caused by P. fluorescens. P. fluorescens was identified from lung biopsy specimens for the first time in this case. According to the antibiotic susceptibility testing (AST) of P. fluorescens, the patient was given ciprofloxacin treatment. The temperature of the patient then returned to normal. Chest CT examination revealed improvements in pulmonary inflammation. CONCLUSIONS: These findings suggest that the patients with pneumonia caused by P. fluorescens should be treated in a timely manner according to the AST results.

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Glioblastoma (GBM) is a difficult-to-treat cancer, likely attributed to the blood brain barrier and drug resistance. Nose-to-brain drug delivery is a direct and non-invasive pathway for brain targeting with low systemic toxicity. Disulfiram (DSF) has shown its effectiveness against GBM, especially with copper ion (Cu). In this work, we designed a DSF loaded ion-sensitive nanoemulsion in situ gel (DSF-INEG) that was delivered intranasally along with Cu to the rat brains for the GBM treatment. The developed DSF-INEG nanomedicine showed a suitable particle size of 63.4 ± 1.1 nm and zeta potential of -23.5 ± 0.2 mV with a favorable gelling ability and prolonged DSF release. The results in vitro indicate DSF-INEG/Cu effectively inhibited the proliferation of both C6 and U87 cells. Besides, the excellent brain-targeting efficacy via nose-to-brain delivery was proved by the highest fluorescence signal of Cy5.5-INEG in the rat brains. Moreover, GFP imaging showed enhanced tumor growth inhibition of the rats by the DSF-INEG/Cu treatment, and their median survival time was 1.6 and 1.2 folds than those of the rats in the control and DSF/Cu treated groups, respectively, with no obvious histopathological damage to normal tissues. Overall, DSF-INEG/Cu could be a promising intranasal nanomedicine for effective GBM treatment.

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The unique environment of brain poses a huge challenge for drug development aimed at combatting glioblastoma (GBM) due to poor organ targeting. Intranasal administration is often considered as an attractive route directly into brain by not only circumventing the blood brain barrier and but also avoiding the hepatic first-pass effect. Disulfiram (DSF) is an old alcohol-aversion drug that has anti-tumor activities against diverse cancer types such as GBM in preclinical studies, especially when it is combined with cupper ion (Cu). In this study, DSF was embedded in hydroxypropyl-ß-cyclodextrin (HP-ß-CD) to prepare a DSF inclusion complex with the enhanced solubility, anti-GBM activity and high safety in vitro. The highest fluorescence signal of Cy5.5/HP-ß-CD in the male rat brains showed the strong brain-targeting of nose-to-brain drug delivery. Therapeutic effects of DSF/HP-ß-CD combined with Cu (DSF/HP-ß-CD/Cu) on intracranial glioma-bearing male rats via different drug delivery routes were then investigated. DSF/HP-ß-CD/Cu administrated by the intranasal route effectively inhibited tumor growth and migration, promoted apoptosis, and achieved 36.8% and 18.2% prolonged median survival time comparing to those of model rats by oral and intravenous administrations, respectively. Moreover, no obvious histopathological damage to normal tissues was observed by H&E staining. Overall, DSF/HP-ß-CD/Cu could be a promising intranasal formulation for the effective GBM treatment.

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INTRODUCTION: In noninvasive positive-pressure ventilation (NPPV), the changes in the expiratory positive airway pressure (EPAP) directly affect the magnitude of the tidal volume. OBJECTIVES: This experimental study aims to verify the precise effects of end-expiratory fluctuation on the body tidal volume to better assist NPPV in clinical practice. METHODS: We selected the TestChest-simulated lung simulation of different populations, including healthy subjects (normal group), patients with chronic obstructive pulmonary disease (COPD) with emphysema as their primary phenotype (COPD1 group), and patients with COPD with bronchitis as their primary phenotype (COPD2 group). RESULTS: Regarding the tidal volume curves of the three groups under various conditions, sixfold charts revealed that the tidal volume changed with the end-expiratory pressure fluctuations. In addition, regression coefficients for end-expiratory pressure fluctuations, (IPAP-EPAP) and (IPAP-EEPAP) exhibited a significant contribution to the tidal volume. The two coefficients in the normal, COPD1 and COPD2 groups were 52.294 and 10.414, 46.192 and -8.816, and 11.922 and 17.947, respectively. The circuit simulation results showed that the simulation curve fitted the experimental curve better by changing the coefficient of the descending edge of the expiratory phase. CONCLUSIONS: The study results suggest that the end-expiratory pressure fluctuation affects the body tidal volume. Compared with the bilevel positive airway pressure (PAP), the trilevel PAP provides additional respiratory support to the body during a respiratory difference in initial respiration and descent.

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To analyze the short-term effects of air pollution on the hospitalization rates of individuals with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), stroke, and myocardial infarction (MI) after adjusting for confounding factors including weather, day of the week, holidays, and long-term trends in Jinan, China.Hospitalization information was extracted based on data from the primary class 3-A hospitals in Jinan from 2013 to 2015. The concentrations of PM2.5, PM10, SO2, NO2, and O3 were obtained from Jinan Environment Monitoring Center. The relative risk and 95% confidence intervals of AECOPD, stroke, and MI were estimated using generalized additive models with quasi-Poisson distribution in the mgcv package, using R software, version 1.0.136.The incremental increased concentrations of particulate pollutants including PM2.5 and PM10 were significantly associated with increased risk of hospitalization of AECOPD, stroke, and MI, and the adverse influences of PM2.5 on these diseases were generally stronger than that of PM10. The incremental increased concentrations of gaseous pollutants including SO2, NO2, and O3 were significantly associated with increased risk of hospitalization of stroke and MI in this population.Air pollution has significant adverse effects on hospitalization rates of individuals with AECOPD, stroke, and MI in Jinan, China.

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OBJECTIVE: We have designed the expiratory positive airway pressure (EPAP) mask to provide a new sort of therapeutic strategies for Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS). And this study aims to assess the safety, efficacy and compliance of the EPAP therapy. METHODS: 40 healthy volunteers were enrolled to measure the end-tidal carbon dioxide pressure (PETCO2) while being treated by EPAP mask. 40 symptomatic moderate or severe OSAHS patients (AHI≥15/h) recruited were equally divided into two groups randomly and treated with CPAP or mask for a week respectively. After a week of washing out, the patients were applied with exchanged therapeutic methods for another week. The PSG was performed at the end of each week of treatment with device-on. RESULTS: There were no significant differences of PETCO2 under different exhaled positive pressure level between CPAP, EPAP therapies and non-therapy for the healthy volunteers (P>0.05). After being treated, among the OSAHS patients in the two groups, the ESS scores and AHI decreased, and minimum SaO2 and mean SaO2 increased significantly (all P>0.05). There was no significant differences of the efficacy between EPAP and CPAP therapy. CONCLUSIONS: EPAP mask therapy was safe and reliable with significant efficacy for selected OSAHS patients. However, the compliance needs further improvement.

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RATIONALE: Bronchobiliary fistula (BBF) is a rare clinical condition which is characterized by a channel between biliary tract and bronchial tree. BBF can present with fever, dyspnea, and cough. However, it can be easily misdiagnosed as biliary vomiting, dyspnea, or even severe pneumonia. PATIENT CONCERNS: A 53-year-old woman was diagnosed with breast cancer in April 2011 and underwent radical mastectomy and lymph node dissection, chemotherapy, and radiotherapy. Unfortunately, the patient suffered from bone metastasis during the 1st year and liver metastasis during the 2nd year after radical mastectomy. In 2013, the patient underwent transcatheter arterial chemoembolization therapy twice for liver metastasis. The patient was then treated with radiofrequency ablation (RFA) in 2016. Unfortunately, the patient developed a cough with bitter-tasting yellow sputum and chest tightness 2 weeks after the RFA treatment. Approximately 6 months later, the patient still complained of a cough with yellow sputum and persistent chest tightness. The patient was then admitted to our department. DIAGNOSES: The presence of bile in the sputum supported a diagnosis of BBF. Bronchoscopy was performed, and the presence of bile in the lavage fluid confirmed the diagnosis of BBF. INTERVENTIONS: The patient was treated with antibiotics including sulbactam, cefoperazone, levofloxacin and meropenem, was well as hepatoprotectants, nutritional support and other supportive treatments in our department. OUTCOMES: The patient died because of liver failure. LESSONS: This case demonstrates that we should consider the possibility of BBF when patients experience a recurrent cough with discolored sputum after RFA. In particular, a diagnosis of BBF should be considered in patients who do not respond to antibiotic treatment.

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Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease that can occur as a unique existence (primary Sjögren's syndrome) or merge with other systemic diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis or systemic sclerosis (secondary Sjögren's syndrome). Data on the two diseases occurrence order are inadequate. Primary Sjögren's syndrome (pSS) may relatively uncommonly lead to diffuse cystic lung changes. We represent a female who was diagnosed pSS with diffuse cystic lung alterations developed SLE two years later. SS was diagnosed on account of the existence of dryness of eye and mouth, Schirmer's test, biopsy of the minor salivary glands of her lip, positive anti-SSA and anti-SSB antibody in the serum. Chest computed tomography image showed bilateral diffuse cystic changes with a wide variation in cyst size and distribution. SLE was finally diagnosed based on bilateral lower limb skin rash, gonarthritis and omarthritis, low level of complement, antinuclear antibody 1:640 and positive antibodies to double-stranded DNA. Improvement was achieved with therapy of corticosteroids, hydroxychloroquine and antibiotics. This report provides us clinical, diagnosis and treatment perception of SS-onset SLE as patient presenting diffuse cystic lung changes.

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INTRODUCTION: Primary tracheobronchial amyloidosis (TBA) is a rare disease of unknown etiology, with a high misdiagnosis rate. The current gold standard diagnostic criteria require double-positive results for Congo red staining and polarized light microscopy examination. OBJECTIVES: The aim of the present report was to examine the diagnostic value of polarized light microscopy in TBA diagnosis in China. METHODS: Thirteen cases from the Shandong University Qilu Hospital were reviewed. Polarized light microscopic examination was conducted after searching for cases with positive Congo red staining. RESULTS: Among the 13 patients, eight displayed yellow-green birefringence body with polarized light microscopic examination. This result indicated a false-positive rate of 38.5% with Congo red staining used as the single criteria for TBA diagnosis. After reviewing the Chinese literature and selecting 104 reported cases of TBA in China, we found that diagnosis with the gold standard was confirmed in <30% patients, which may lead to misdiagnosis and delayed treatment. CONCLUSION: The universal use of polarized light microscopy in China is currently limited, and there is a big gap from the international diagnosis standards. There is a need to include polarized light microscopy in routine TBA diagnosis to reduce the misdiagnosis rate, and achieve optimal treatment.

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The present study was designed to examine the expression and function of matrix metalloproteinase­19 (MMP­19), which is downregulated following respiratory syncytial virus (RSV) infection. The diverse expression levels of MMP were examined using a designed cDNA expression array. The expression and secretion of MMP­19 was examined using reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis and ELISA, respectively. The proliferation of epithelial cells and lung fibroblasts were examined using flow cytometry. The epithelial­mesenchymal transition (EMT) was also examined by performing western blot and RT­qPCR analyses. The results of the cDNA assay showed that infection with RSV resulted in the abnormal expression of certain metalloproteinases. Among these, the expression of MMP­19 decreased 3 and 7 days following infection. By using flow cytometric, western blot and RT­qPCR analyses, the present study demonstrated that the downregulation of MMP­19 inhibited the proliferation of epithelial cells, promoted the EMT and induced the proliferation of lung fibroblasts. Taken together, the findings of the present study suggested that the downregulation of MMP­19 following RSV infection may be associated with the development of airway hyper­responsiveness.

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