used at the primary-care settings in China to assess asthma control.

Objective To compare the inspiratory cycling-off synchronization with expiratory trigger sensitivity (ETS) setting during noninvasive pressure support ventilation (PSV) under the different conditions of respiratory mechanics. Methods Bi-level pressure ventilator was connected to a lung model (Hans Rudolph Series1101 simulator). And its mechanics was set to normal, obstructive and restrictive ventilation dysfunction. Tests were performed with pressure support levels of 10 (in normal condition, 1 cmH2O = 0.098 kPa) and 15 cmH2O, 5 cmH2O positive end-expiratory pressure (PEEP). The data including cycling delay time (Td), tidal volume (TV) and airflow were collected in the presence of air leaks (24-28 L/min). Results Significant performance on airflow was observed in various respiratory mechanics conditions. The peak inspiratory flow (PIF) and peak expiratory flow (PEF) were different, and the tidal volume, PEF and inspiratory time were increased after decreasing the ETS level. Premature cycling occurred frequently in normal and restrictive model. Delay cycling was found only when the ETS setting was at the lowest level (about 5% of PIF), at which Td were (15.20 ± 0.43) ms and (105.00 ± 15.82) ms. In obstructive model, PIF and PEF were significantly decreased, and delay cycling was always present. Td were increased after the ETS setting was changed from the most sensitive level to moderate level:(51.30 ± 12.63) ms vs. (162.40 ± 15.59) ms, as cycling-off criteria were reduced from (34.52 ± 3.36)% to (16.04 ± 2.58)% of PIF, and there were statistical differences (P<0.05). Severe delay cycling was found when the ETS level was at the lowest level. Conclusions There are significant differences in performances and cycling-off synchrony in various respiratory mechanics models during PSV. For Curative Flexo ST30 bi-level pressure ventilator, its flow cycling-off criteria range is about 5%-35%of PIF. The higher ETS level might be beneficial to improve patient-ventilator synchrony in patients with obstructive airway diseases, which could result in premature cycling in patients with restrictive disease.

Objective To observe the benefits and safety of low-dose azithromycin maintenance treatment on pulmonary function and quality of life in patients with bronchiectasis. Methods Thirty-seven adult bronchiectasis patients accompanied with chronic purulent respiratory tract symptoms were selected, and all the patients were given azithromycin 250 mg oral, once/d for 12 months. The respiratory symptoms, pulmonary function and quality of life before treatment and 16, 52 weeks after treatment were observed. Results Among 37 patients with bronchiectasis, 3 cases were lost, 1 case was in the follow-up of the 16th week, and 2 cases exited because of acute exacerbation. There were no statistical differences in body mass index (BMI) and inspiratory capacity percentage of estimated value (IC%Pred) before treatment, 16 and 52 weeks after treatment (P>0.05). The C-reactive protein (CRP), forced expiratory volume in 1 second (FEV1)/ forced ventilatory capacity (FVC), forced expiratory flow between 25% and 75% of vital capacity percentage of estimated value (FEF25-75%Pred), modified British medical research council dyspnea scale (mMRC) score 16 and 52 weeks after treatment were significantly better than those before treatment:(15.33 ± 4.00) and (9.21 ± 3.04) mg/L vs. (25.59 ± 9.82) mg/L, (75.94 ± 5.59)%and (75.52 ± 7.06)% vs. (72.14 ± 5.62)%, (60.22 ± 10.90)% and (63.73 ± 6.54)% vs. (55.44 ± 9.16)%, (1.75 ± 0.69) and (1.41 ± 0.56) scores vs. (2.19 ± 0.74) scores;the low respiratory tract infection visual analog scale (LRTI- VAS) score, FEV1 percentage of estimated value (FEV1% Pred) and chronic obstructive pulmonary disease assessment test (CAT) score 52 weeks after treatment were significantly better than those before treatment: (17.74 ± 3.76) scores vs. (21.57 ± 4.47) scores, (70.31 ± 4.07)% vs. (66.95 ± 5.48)%and (18.06 ± 3.32) scores vs. (21.54 ± 4.89) scores, and there were statistical differences (P<0.05). In the course of treatment, 5 cases might be associated with the drug adverse reactions, but the symptoms were mild. No patients exited because of adverse reaction. Five patients had 7 episodes of acute exacerbation, among whom 2 cases exited and the other 3 cases did not interrupt azithromycin treatment during acute exacerbation. Conclusions For adult patients with bronchiectasis, the long-term treatment of low-dose azithromycin (250 mg/d) can improve the respiratory symptoms and quality of life, and reduce the airflow limitation of peripheral airway.

AIM: To observe the changes in heme oxygenase-1(HO-1) expression in the lung after ischmia-reperfusion of hind limbs in rats.METHODS: Hind limbs ischemia was made by clamping infrarenal aorta with a microvascular clip and lung injury was made by following reperfusion. Lung tissue was obtained from the animals subjected to sham operation, 4 h ischemia without reperfusion and 4 h, 8 h, 16 h, 24 h, 48 h reperfusion following 4 h ischemia. The levels of HO-1 mRNA and protein were measured at different times by Northern blot and Western blot. Immunohistochemistry technique was used to determine the cell types responsible for limb ischemic reperfusion induced HO-1 expression. RESULTS: After ischemia-reperfusion of limbs, HO-1 mRNA increased by 4 h, reached a peak at 16 h, and returned toward baseline at 24-48 h. This time course correlated with increased HO-1 protein. Immunohistochemical studies showed HO-1expressed in a variety of cell types, including the airway epithelium, alveolar macrophages and vascular smooth muscular cells. There were no positive signals in sham group and ischemia group both in mRNA levels and protein levels. CONCLUSION: The expression of HO-1 in the lung is not induced by limb ischemia or sham operation, but induced by limb reperfusion after ischemia in rats.

The purpose of the study was to find out how to enter the preliminary Qigong simulation state in a short period of time.

AIM:To observe the changes in heme oxygenase-1(HO-1) expression in the lung after ischmia-reperfusion of hind limbs in rats.METHODS:Hind limbs ischemia was made by clamping infrarenal aorta with a microvascular clip and lung injury was made by following reperfusion. Lung tissue was obtained from the animals subjected to sham operation, 4 h ischemia without reperfusion and 4 h, 8 h, 16 h, 24 h, 48 h reperfusion following 4 h ischemia. The levels of HO-1 mRNA and protein were measured at different times by Northern blot and Western blot. Immunohistochemistry technique was used to determine the cell types responsible for limb ischemic reperfusion induced HO-1 expression. RESULTS:After ischemia-reperfusion of limbs, HO-1 mRNA increased by 4 h, reached a peak at 16 h, and returned toward baseline at 24-48 h. This time course correlated with increased HO-1 protein. Immunohistochemical studies showed HO-1expressed in a variety of cell types, including the airway epithelium, alveolar macrophages and vascular smooth muscular cells. There were no positive signals in sham group and ischemia group both in mRNA levels and protein levels. CONCLUSION:The expression of HO-1 in the lung is not induced by limb ischemia or sham operation, but induced by limb reperfusion after ischemia in rats.

Objective To observe the benefits and safety of different maintenance doses of azithromycin for long-term treatment in adult patients with non-cystic fibrosis (CF) bronchiectasis. Methods One hundred and thirty-two indigenous outpatients (>18 years old) with stable non-CF bronchiectasis were enrolled. All patients were randomly assigned to a control group and two treatment groups. Patients in the azithromycin fixed-dose treatment group received oral azithromycin (250 mg daily) and ambroxol hydrochloride (30 mg, 3 times/d). Azithromycin progressively decreased dosage treatment group received oral azithromycin (250 mg daily for 8 weeks-250 mg 3 times/week for 8 weeks-250 mg 2 times/week for 10 weeks) and ambroxol hydrochloride (30 mg, 3 times/d). Subjects in control group only received ambroxol hydrochloride therapy. The course of treatment lasted for 26 weeks. Spirometry, exacerbations, sputum microbiology, quality of life, dyspnea scores and adverse effects were monitored after treatment for 26 weeks. Results One hundred and twenty-nine evaluable subjects completed the study. After treatment, the level of percentage of estimated value forced expiratory volume in 1 second (FEV1% Pred) in azithromycin fixed-dose treatment group and azithromycin progressively decreased dosage treatment group was significantly higher than that before treatment: (83.01 ± 5.79)% vs. (79.39 ± 3.53)%, (84.97 ± 5.10)% vs. (80.94 ± 3.46)%, P<0.05. Forced expiratory flow between 25% and 75% of vital capacity (FEF25%- 75%) was also increased in two groups: (54.87 ± 5.72) % vs. (51.86 ± 8.16)%, (55.65 ± 3.39)% vs. (53.46 ± 5.75)% , there was significant difference (P<0.05). But the levels of above parameters between two groups after treatment had no significant differences (P >0.05). The parameters of FEV1% Pred, forced expiratory volume in 1 second (FEV1)/forced ventilatory capacity (FVC) and FEF25%-75%were lower compared to those before treatment in the control group (P <0.05). However, the scores of LRTI-VAS and FACED in control group after treatment were decreased slightly: (20.55 ± 1.76) scores vs. (21.34 ± 1.86) scores, P<0.05; (4.16 ± 0.75) scores vs. (4.36 ± 0.72) scores, P > 0.05. Seven episodes of acute exacerbation was occured during 26 weeks, 2 cases exited. The others did not interrupt azithromycin treatment during acute exacerbation. Drug-related adverse reactions were mild. Conclusions For adult stable patients with non-CF bronchiectasis, the clinical symptoms and airflow limitation are improved after long-term treatment of low-dose azithromycin. Similar effects on FACED score and LRTI-VAS score are observed in patients with progressively decreased dosage of azithomycin.

Objective: To explore the role of D-dimer level in patients with acute exacerbation of chronic obstructive disease (AECOPD) in predicting the re-admission of patients. Methods: One hundred and twenty chronic obstructive pulmonary disease (COPD) patients in the Shanghai General Hospital of Shanghai Jiao Tong University form January 2016 to December 2018 were divided into AECOPD group (62 cases) and stable COPD group (58 cases).The level of serum D-dimer was analyzed and Pearson correlation analysis was performed with the patient′s blood gas analysis and COPD assessment test (CAT) score. The area under the receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum D-dimer level for readmission. Results: Serum D-dimer level was significantly higher in AECOPD group than that in stable group: (1.24 ± 0.56) mg/L vs. (0.39 ± 0.22) mg/L, and there was statistical difference (P<0.01). Serum D-dimer level was negatively correlated with PaO₂ in COPD patients (r = 0.712, P = 0.000), but positively correlated with PaCO₂ (r = 0.683, P = 0.000) and CAT score (r = 0.652, P = 0.000). The area under the ROC curve of D-dimer level to re-admission of COPD patients within one year was 0.848. The cutoff value was 1.015 mg/L. Conclusions The level of D-dimer in COPD patients is of great value in predicting the re-admission of patients, which can be used as an independent indicator of disease progression.

Mevalonate metabolism plays an important role in regulating tumor growth and progression; however, its role in immune evasion and immune checkpoint modulation remains unclear. Here, we found that non-small cell lung cancer (NSCLC) patients with higher plasma mevalonate response better to anti-PD-(L)1 therapy, as indicated by prolonged progression-free survival and overall survival. Plasma mevalonate levels were positively correlated with programmed death ligand-1 (PD-L1) expression in tumor tissues. In NSCLC cell lines and patient-derived cells, supplementation of mevalonate significantly up-regulated the expression of PD-L1, whereas deprivation of mevalonate reduced PD-L1 expression. Mevalonate increased CD274 mRNA level but did not affect CD274 transcription. Further, we confirmed that mevalonate improved CD274 mRNA stability. Mevalonate promoted the affinity of the AU-rich element-binding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA. By in vivo study, we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1, increased the infiltration of CD8⁺ T cells, and improved cytotoxic function of T cells. Collectively, our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody, and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.

[This corrects the article DOI: 10.1016/j.apsb.2023.04.002.].