Objective:To explore the application value of problem-based learning (PBL) controlled by closed-loop feedback in the teaching of respiratory medicine.Methods:In PBL teaching, after students' open inquiry, discussion and PBL self-study, closed-loop feedback was given by organizing PPT report, written summary and mechanism diagram display of medical students. The participation of teachers and students, teaching quality, the degree of students' identification of key knowledge points, the breadth and depth of mastering the characteristics of key symptoms and the satisfaction of PBL teaching work were investigated, and the differences were compared before and after the closed-loop feedback. GraphPad Prism 5.01 was used in the analysis.Results:It was found that closed-loop feedback could improve the self-evaluation of tutor's teaching participation [(7.97±0.91) vs. (8.77±0.64), P < 0.001] and students' evaluation on teaching participation of tutor [(8.09±0.79) vs. (8.74±0.45), P < 0.001]. At the same time, students' evaluation on the teaching quality of tutors was also improved [(88.61±6.53) vs. (92.59±5.44), P < 0.001]. After closed-loop feedback, the students' identification of the required knowledge points in the syllabus was significantly increased [(84.00±21.75) vs. (90.22±16.18), P = 0.017]. The overall satisfaction with PBL teaching was also improved obviously [(8.93±0.67) vs. (9.37±0.64), P < 0.001]. Conclusion:Practice has proved that the closed-loop controlled PBL teaching approach has a good effect on the teaching of respiratory medicine, and it's worth popularizing in clinical teaching.

BACKGROUNDThe efficacy of montelukast (MONT), a cysteinyl leukotriene receptor antagonist, in nonasthmatic eosinophilic bronchitis (NAEB), especially its influence on cough associated life quality is still indefinite. We evaluated the efficacy of MONT combined with budesonide (BUD) as compared to BUD monotherapy in improving life quality, suppressing airway eosinophilia and cough remission in NAEB.

METHODSA prospective, open-labeled, multicenter, randomized controlled trial was conducted. Patients with NAEB (aged 18-75 years) were randomized to inhaled BUD (200 μg, bid) or BUD plus oral MONT (10 μg, qn) for 4 weeks. Leicester cough questionnaire (LCQ) life quality scores, cough visual analog scale (CVAS) scores, eosinophil differential ratio (Eos), and eosinophil cationic protein (ECP) in induced sputum were monitored and compared.

RESULTSThe control and MONT groups contained 33 and 32 patients, respectively, with similar baseline characteristics. Significant with-in group improvement in CVAS, LCQ scores, Eos, and ECP was observed in both groups during treatment. After 2-week treatment, add-on treatment of MONT was significantly more effective than BUD monotherapy for CVAS decrease and LCQ scores improvement (both P < 0.05). Similar results were seen at 4-week assessment (both P < 0.05). 4-week add-on therapy of MONT also resulted in a higher percentage of patients with normal sputum Eos (<2.5%) and greater decrease of ECP (both P < 0.05).

CONCLUSIONSMONT combined with BUD was demonstrated cooperative effects in improvement of life quality, suppression of eosinophilic inflammation, and cough remission in patients with NAEB.

Acetates ; therapeutic use ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bronchitis ; drug therapy ; immunology ; Budesonide ; therapeutic use ; Cough ; drug therapy ; Female ; Humans ; Inflammation ; drug therapy ; Male ; Middle Aged ; Quality of Life ; Quinolines ; therapeutic use ; Young Adult

Objective:To investigate the effects of different doses of vitamin D diet early in life on airway inflammation in different endotypes of asthma mice models.Methods:In the Animal House of Shanghai General Hospital of Nanjing Medical University in June 2022, the BALB/c mice with 14 d pregnant were selected, the offspring mice were divided into vitamin D sufficient group and vitamin D deficient group by random number table method with 12 each. The mice in the vitamin D sufficient group were given a feed with sufficient vitamin D content, while the mice in the vitamin D deficient group were given a feed without vitamin D. At the age of 8 weeks, the mice were sensitized and stimulated with ovalbumin to establish a T2 type asthma model, while the mice were sensitized and stimulated with ovalbumin combined with ozone exposure to establish a non-T2 type asthma model, with 6 mice in each model. The level of serum 25 hydroxy vitamin D 3 was detected by enzyme-linked immunosorbent assay (ELISA) method. The lung tissue was stained with HE to evaluate the inflammatory response score and calculate the eosinophils density and neutrophils density. In bronchoalveolar lavage fluid (BALF), the expression levels of interleukin (IL)-4, IL-6, IL-10 and IL-17A, the inflammatory cell count (total cell count, neutrophil count and eosinophil count) were detected. Results:The 25 hydroxy vitamin D 3 in T2 type asthma mice and non-T2 type asthma mice of vitamin D deficient group were significantly lower than that in vitamin D sufficient group: (8.12 ± 1.72) μg/L vs. (26.63 ± 2.54) μg/L and (6.86 ± 1.65) μg/L vs. (23.81 ± 3.09) μg/L, and there was statistical difference ( P<0.01). The inflammatory response score in non-T2 type asthma mice of vitamin D deficient group was significantly higher than that in non-T2 type asthma mice of vitamin D sufficient group: (2.58 ± 0.49) scores vs. (1.83 ± 0.21) scores, and there was statistical difference ( P<0.05), there was no statistical differences in inflammatory response score in T2 type asthma mice between two groups ( P>0.05). The neutrophils density and eosinophils density in T2 type asthma mice and non-T2 type asthma mice of vitamin D deficient group were significantly higher than those in vitamin D sufficient group, T2 type asthma mice: (20.30 ± 1.95) cells/100 μm vs. (12.58 ± 1.04) cells/100 μm and (5.25 ± 0.62) cells/100 μm vs. (3.15 ± 0.35) cells/100 μm; non-T2 type asthma mice: (53.48±5.19) cells/100 μm vs. (33.80 ± 2.74) cells/100 μm and (3.00 ± 0.29) cells/100 μm vs. (2.17 ± 0.21) cells/100 μm, and there were statistical differences ( P<0.01 or <0.05). The BALF total cell count in T2 type asthma mice and non-T2 type asthma mice of vitamin D deficient group was significantly higher than that in vitamin D sufficient group, the BALF eosinophil count in T2 type asthma mice of vitamin D deficient group was significantly higher than that in T2 type asthma mice of vitamin D sufficient group, the BALF neutrophil count in non-T2 type asthma mice of vitamin D deficient group was significantly higher than that in T2 type asthma mice of vitamin D sufficient group, and there were statistical differences ( P<0.01); there was no statistical difference in BALF neutrophil count in T2 type asthma mice between two groups ( P>0.05); there was no statistical difference in BALF eosinophil count in non-T2 type asthma mice between two groups ( P>0.05). The BALF total cell count and neutrophil count in non-T2 type asthma mice of both groups were significantly higher than those in T2 type asthma mice, but the BALF eosinophil count in T2 type asthma mice was significantly higher non-T2 type asthma mice, and there were statistical differences ( P<0.05). The BALF IL-4, IL-6 and IL-17A in T2 type asthma mice and non-T2 type asthma mice of vitamin D deficient group were significantly higher than those in vitamin D sufficient group, the BALF IL-10 was significantly lower than those in vitamin D sufficient group, and there were statistical differences ( P<0.01 or <0.05). In vitamin D deficient group, the BALF IL-4 in non-T2 type asthma mice was significantly lower than that in T2 type asthma mice, the BALF IL-6 and IL-17A were significantly higher than those in T2 type asthma mice, and there were statistical differences ( P<0.05); in vitamin D sufficient group, the BALF IL-6 and IL-17A in non-T2 type asthma mice were significantly higher than those in T2 type asthma mice, and there were statistical differences ( P<0.05). Conclusions:Vitamin D deficiency is involved in different mechanisms of airway inflammation in T2 type asthma and non-T2 type asthma, and this effect may be more obvious for non-T2 type asthma.

Objective:To compare the effects of extrafine-particle versus fine-particle inhaled corticosteroids (ICS) combined with formoterol on clinical symptoms, airway inflammation and airway function in patients with bronchial asthma (referred to as asthma).Methods:This prospective, randomized controlled clinical trial enrolled a total of 111 patients diagnose of asthma and cough variant asthma with forced expired volume in one second (FEV 1) percentage of predicted (FEV 1%pred) >70% in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from November 2020 to October 2022. The patients were divided into observation group (57 cases) and control group (54 cases) by random digits table method. The patients in observation group were treated with extrafine-particle ICS combined with formoterol, while the patients in control group were treated with fine-particle ICS combined with formoterol. Both groups were treated for 4 weeks. During treatment 10 patients lost follow up and a total of 101 patients complete the final study: 52 cases in observation group and 49 cases in control group. At baseline, the asthma control test (ACT) score was calculated to evaluate the clinical symptoms, fractional exhaled nitric oxide (FeNO) was applied to evaluate the airway inflammatory level, and the pulmonary function test and bronchodilation test were perfromed. The symptom relief time was record. After treatment, all of the parameters were reevaluated. Results:The FEV 1, peak expiratory flow (PEF), forced expired flow at 50% of forced vital capacity (MEF 50), forced expired flow at 25% of forced vital capacity (MEF 25), maximal expiratory flow-volume curve (MMEF) and ACT score after treatment in both groups were significantly improved compared to baseline, and there were statistical differences ( P<0.01). The improvement of ACT score in observation group was significantly higher than that in control group: (5.90 ± 2.25) scores vs. (4.10 ± 2.18) scores, and there was statistical difference ( P<0.01); there were no statistical differences in the symptom relief time and the improvement rates of FEV 1, PEF, MEF 50, MEF 25, MMEF between the two groups ( P>0.05). Further subgroup analysis was performed on 78 patients with small airway dysfunction, 39 patients were treated with extrafine-particle ICS combined with formoterol (observation subgroup), and 39 patients were treated with fine-particle ICS combined with formoterol (control subgroup). The improvement of ACT score in observation subgroup was significantly higher than that in control subgroup: (6.05 ± 2.22) scores vs. (3.95 ± 2.19) scores, and there was statistical difference ( P<0.01); there were no statistical differences in the symptom relief time and the improvement rates of FEV 1, PEF, MEF 50, MEF 25, MMEF between the two subgroups ( P>0.05). Spearman correlation analysis result showed that the improvement rates of MEF 50, MEF 25 and MMEF after treatment were positive correlated with baseline bronchodilator responses of FEV 1, FEV 1/FVC, MEF 50, MEF 25, MMEF ( r = 0.22 to 0.58, P<0.05), but not with baseline bronchodilator responses of PEF ( P>0.05). In terms of safety, neither of the two treatments had major adverse reactions that affect treatment. Conclusions:For asthma patients with baseline FEV 1%pred>70%, the extrafine-particle ICS combined with formoterol has more significantly improved of clinical symptoms compared to fine-particle ICS combined with formoterol, and potentially with better safety profile. The improvement ratio of small airway function parameters in baseline bronchodilation test could potentially predict treatment response.

Objective:To investigate the distribution of the total IgE, and their relationship with allergens and peripheral blood eosinophils in patients with allergic.Methods:The cross-sectional study was used, and 1 417 patients with allergic in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine were selected. The serum total IgE was detected by enzyme-linked immunosorbent assay (ELISA), and the total IgE>60 kU/L was increased. The blood routine was detected by automated hematology analyzer. Using inhalant allergens and food allergens specific IgE antibody detection kits, the serum or plasma allergen-specific IgE antibodies were detected by Oumeng imprinting in vitro semi quantitative method.Results:Among 1 417 patients with allergic, elevated total IgE was in 617 cases (43.54%), normal total IgE in 800 cases (56.46%); 749 cases (52.86%) were allergic, the most common inhalation allergen was dust mite (38.72%, 218/563), and the most common food allergen was peanut (24.01%, 109/454). The rate of normal total IgE, eosinophils and non allergic was 19.20% (272/1 417). The male proportion, ratio of eosinophils, eosinophils count, total index of inhaled allergens, total index of non inhaled allergens, number of positive allergens, total positive index and average positive index in patients with elevated total IgE were significantly higher than those in patient with normal total IgE, the age was significantly lower than that in patients with normal total IgE, and there were statistical differences ( P<0.01). The total IgE<60 kU/L (normal total IgE) was in 800 cases, total IgE from 60 to 499 kU/L (mild elevation of total IgE) in 487 cases, total IgE from 500 to 999 kU/L (moderate elevation of total IgE) in 78 cases, total IgE≥1 000 kU/L (severe elevation of total IgE) in 52 cases. The male proportion and age in patients with sever elevation of total IgE and moderate elevation of total IgE were significantly higher than those in patients with mild elevation of total IgE and normal total IgE, and there were statistical differences ( P<0.05). The compound allergy rate in patients with severe elevation of total IgE was significantly higher than that in patients with moderate elevation of total IgE, mild elevation of total IgE and normal total IgE: 73.08% (38/52) vs. 60.26% (47/78), 38.40% (187/487), 17.00% (136/800), and there was statistical difference ( P<0.05). The ratio of eosinophils, eosinophils count and number of positive allergens increased with increasing total IgE level, and there was statistical difference ( P<0.05). The number of dermatophagoides/dermatophagoides culinae allergic in patients with moderate elevation of total IgE was significantly more than that in patients with sever elevation of total IgE, mild elevation of total IgE and normal total IgE, and there was statistical difference ( P<0.05). Conclusions:Allergic disease may show a normal level of total IgE. Males are more likely to be troubled with high level of IgE. Patients with total IgE ≥1 000 kU/L should be alert to the possibility of poly-sensitization. Total IgE was no longer correlated with individual allergy severity in patients with total IgE≥500 kU/L.

OBJECTIVE：To establish a method for concentration determination of anlotinib in human plasma and apply it in the clinic. METHODS ：The plasma samples were pretreated by salting-out assisted with liquid-liquid extraction with ammonium acetate as salting out assistant and acetonitrile as solvent. Using voriconazole as internal standard ，LC-MS/MS method was adopted. The separation was performed on Waters X Bridge C 18 column with mobile phase consisting of 0.2％ formic acid solution- acetonitrile（gradient elution ）at the flow rate of 1 mL/min. The column temperature was set at 40 ℃，and sample size was 10 μL. The split ratio was 3∶7. The electrospray ion source and multiple reaction monitoring mode were used for the analysis. The ion pair of anlotinib and internal standard under positive ion mode were m/z 408.3→339.3 and m/z 350.2→281.3，respectively. RESULTS ： Anlotinib showed a good linear relationship in the concentration range of 0.2-200 ng/mL（R2＞0.996 7）. The lowest limit of quantitation was 0.2 ng/mL. Intra-day and inter-day RSDs were no more than 12％ （n＝6 or n＝3）. Accuracies were 90.92％-108.00％（n＝6 or n＝3）. The average extraction recoveries were 87.51％-100.00％（RSD＜8％，n＝6）. The average matrix effects were 96.66％-99.93％（RSD＜5％，n＝6）. The plasma concentration of 3 patients with NSCLC treated with anlotinib was 8.74-65.60 ng/mL. CONCLUSIONS ：The method is simple ，accurate and specific ，and is suitable for the plasma concentration monitoring of anlotinib in NSCLC patients.

BACKGROUND: To date, there is no effective treatment for thromboangiitis obliterans (TAO). Anlotinib, as a third-line therapy, is recommended for patients with refractory advanced non-small cell lung cancer (NSCLC). We presented a case report of a patient suffering from right lung squamous cell carcinoma combined with thromboangiitis obliterans, and analyzed the treatment dilemma, which provided a new idea for the treatment of these two diseases. METHODS: A patient of right lung squamous cell carcinoma complicated with TAO was admitted to the department of respiratory and critical care medicine of the Shanghai General Hospital in August 2018. The diagnosis and treatment was retrospectively analyzed, and the literature was reviewed. RESULTS: The 73-year-old male patient complained of cough and sputum for 5 months and was diagnosed with NSCLC (T4N2M0, stage IIIb, performance status score 2) in right upper lung by tracheoscopy biopsy. Pigmentation in both lower extremities accompanied by weakened pulse of dorsal foot artery was confirmed. He had a history of smoking, and suspected vascular intermittent claudication and wandering phlebitis for more than one year. Ultrasound indicated multiple arterial occlusion in both upper and lower extremities and deep venous thrombosis in lower extremities. TAO was diagnosed. Peripherally inserted central catheter (PICC) implantation and intravenous infusion post implantation failed and he could not receive chemotherapy. Vascular endothelial growth factor (VEGF) signal pathway dysfunction is also involved in TAO. Anlotinib (12 mg qd po) was selected for treatment NSCLC and TAO, accordingly. He had partial response (PR) and the cancer kept stable for 14 months. At the same time, TAO improved. CONCLUSIONS Anlotinib effectively controlled the growth of NSCLC and improved TAO related symptoms. Anlotinib maybe normalize disordered growth of blood vessels through the VEGF signaling pathway, rather than simply inhibiting angiogenesis.