AIM:To examine the impact of the transcription factor 7 analogue 2(TCF7L2)gene polymorphism on the hypoglycaemic effect of ex-enatide in patients with type 2 diabetes mellitus(T2DM).METHODS:A total of 100 newly diagnosed Han Chinese patients with T2DM who had not re-ceived any drug treatment were selected from the Affiliated Hospital of Xuzhou Medical University and treated with exenatide monotherapy for 6 months.The TCF7L2 rs290487 was genotyped by SnaPshot method,and blood glucose levels,lipids profiles and pancreatic function evaluation indica-tors were measured at baseline,3 months and 6 months after exenatide treatment.Multiple linear regression analysis was employed to assess the cor-relation between each indicator and the reduction in glycated hemoglobin(HbA1c)levels after 6 months of exenatide treatment.The expression of TCF7L2 protein in the plasma of T2DM patients was detected by enzyme-linked immunosorbent assay(ELISA)kit.Furthermore,western blotting was con-ducted to ascertain TCF7L2 expression in pancreat-ic tissues obtained from db/db mice and INS-1 cells cultured under high glucose conditions.Lentivirus transfection was used to overexpress or knock down TCF7L2 in insulinoma cell line(INS-1)cells,followed by measurement of KSIS activity and insu-lin content after a 24-hour intervention with exena-tide.RESULTS:The distribution pattern of TCF7L2 rs290487 was found to be in accordance with Har-dy-Weinberg equilibrium(P＞0.05).Following 6 months of exenatide treatment,there was a nota-ble reduction in blood glucose levels and an im-provement in lipid profiles when compared to base-line values.Additionally,there was a significant in-crease in the homeostasis model assessment of be-ta-cell function(HOMA-B)values.Patients with the TT genotype exhibited significantly lower postpran-dial plasma glucose(PPG)levels and HbA1c values compared to those with the CC or CT genotypes(P＜0.05).After adjusting for age,gender,body mass in-dex(BMI),and waist to hip ratio(WHR)in the mul-tiple linear regression model,a significant associa-tion was observed between the rs290487 TT geno-type,baseline HbA1c levels,and family history of diabetes with the reduction in HbA1c after six months of exenatide treatment(P＜0.05).Further-more,individuals with the rs290487 TT genotype demonstrated a notable elevation in TCF7L2 expres-sion in plasma among T2DM patients in comparison to those with the CC genotype(P＜0.05).In particu-lar,pancreatic tissue from db/db mice exhibited markedly elevated TCF7L2 expression compared to db/m mice.However,this up-regulation was re-versed by exenatide treatment.Similarly,INS-1 cells cultured under high glucose conditions dem-onstrated an increase in TCF7L2 expression,which was ameliorated upon exenatide administration.The knockdown of TCF7L2 using shRNA enhanced the KSIS function of pancreatic β cells and aug-mented the insulinotropic effect of exenatide.Con-versely,the upregulation of TCF7L2 impaired the KSIS function of pancreatic β cells and attenuated the insulinotropic effect of exenatide.CONCLU-SION:The TCF7L2 rs290487 gene polymorphism is closely associated with the hypoglycaemic efficacy of exenatide therapy.The risk allele C may diminish the effectiveness of exenatide by impacting the lev-els of PPG and HbA1c in T2DM patients.The muta-tion at TCF7L2 rs290487 site(C→T)influenced the expression of TCF7L2 protein.By exerting its regula-tory effect,exenatide may be capable of regulating the impact of TCF7L2 on the function of pancreaticβ cells.

AIM: To observe the effect of fudosteine on induced sputum cell components and lung function in patients with stable neutrophil-dominated COPD. METHODS: From October 2019 to October 2022, 53 patients with stable COPD were selected and divided into fudosteine group and placebo group. The placebo group was treated with routine treatment, and the fudosteine group was treated with fudosteine on the basis of routine treatment. The two groups were treated for 6 months. The clinical symptoms [Saint George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT) and Modified British Medical Research Council Dyspnea scale (MMRC), Breathlessness, Cough, and Sputum Scale (BCSS)], lung function index, induced sputum cytology analysis and other related examination results were recorded in detail before and after treatment. RESULTS: (1) Compared with the baseline, the forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and the ratio of FEV1 to FVC (FEV1/FVC) of the two groups were improved after treatment, and the differences were statistically significant (P<0.05). However, after treatment, there was no significant difference in pulmonary function between the two groups except for the percentage of carbon monoxide diffusion in the predicted value (DLCO%pre) (DLCO%pre in the fudosteine group was higher than that in the placebo group). (2) After treatment, the total number of induced sputum cells and neutrophil counts in the fudosteine group were lower than those in the placebo group. Compared with the number of cells in each component at baseline, the total number of induced sputum cells and neutrophil count in the fudosteine group were significantly lower (P< 0.05). CONCLUSION: Fudosteine treatment in patients with stable neutrophil-dominated COPD can improve lung function, reduce the total number of induced sputum cells and the total number of neutrophils, thereby improving airway inflammation.

Induced sputum testing is a non-invasive test that reflects the nature and extent of airway inflammation and plays an important role in the diagnosis, treatment and prognosis of chronic airway diseases. This article outlines the development history of induced sputum technology, introduces the principle and operation of induced sputum technology, evaluates its safety, summarizes the three main test components, elaborates the role of this technology in various chronic airway diseases, such as reflecting the type of airway inflammation, predicting the efficacy of medication, and combining it with transcriptomics to study disease mechanisms, and briefly summarizes its innovations and makes a vision for the future.

Chronic obstructive pulmonary disease (COPD) is the most common chronic airway disease. The current status of treatment based mainly on bronchodilators and ICS is not sufficient for all of COPD patients. Various studies have attempted to use biologics targeting specific cytokines and their receptors in COPD patients to alleviate respiratory symptoms or reduce the risk of acute exacerbations. However, they failed to bring significant clinical benefits. More studies are needed to further determine the efficacy of targeted biotherapy for COPD.

Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease. It has been reported in the literature that COPD patients with chronic airway mucus hypersecretion have more frequent acute exacerbations, more severe lung function decline, and higher hospitalizations and mortality. Therefore, it is particularly critical to understand the pathogenesis of hypersecretion of mucus in chronic obstructive pulmonary disease and find out effective treatment. This article focuses on the structure, significance of airway mucus and the mechanism of hypersecretion of mucus in chronic obstructive pulmonary disease (COPD). In addition, we also summarized drug and non-drug therapy for chronic airway mucus hypersecretion in this article. Drug therapy includes traditional drug therapy, some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy, and non-drug therapy includes smoking cessation, physical therapy and bronchos-copy therapy. We hope that it will provide new ideas and directions for the treatment of mucus hypersecretion in COPD patients.

AIM: To investigate the clinical features of acute exacerbation chronic obstructive pulmonary disease (AECOPD) of complicated with type 2 diabetes mellitus (T2DM), and analyze the related clinical features and risk factors. METHODS: This was a single-center cross-sectional study. From March 2020 to January 2023, 479 hospitalized patients with AECOPD in the department of respiratory and critical care medicine, Suining Central Hospital were included. There were 215 patients in AECOPD group and 60 patients in AECOPD with T2DM group. The collected variables included demographic data, complications, blood routine, infection index, random blood glucose, blood gas analysis and lung function. The adoption rate and constituent ratio of the basic description classification data were expressed as mean standard deviation for the normal distribution measurement data and median interquartile range for the skew distribution measurement data. T-test was used for normal distribution and non - parameter test was used for non-normal distribution. The categorical variables were tested by chi-square test. Rank sum test was used for rank variable data. Binary logistic regression model was used to investigate the independent factors associated with T2DM in patients with AECOPD. Finally, the results of logistic regression were verified and visualized by nomogram, validation curve, ROC curve and DCA curve. P<0.05 was a significant statistical difference. RESULTS: Univariate analysis showed that there were significant differences in body mass index (BMI), essential hypertension, coronary heart disease, atrial fibrillation (AF), pulmonary function (GOLD stage), blood neutrophil (NS), blood lymphocyte (LYM), arterial blood gas PaCO2, Alanine transaminase (ALT) and random blood glucose (RBG) between the two groups (P<0.05). The binary logistic regression model (C-index=0.847) was constructed with the above 10 variables, the results showed that BMI (OR=1.309), Af (OR= 8.188), LYM counts (OR=0.474), PaCO2 (OR=1.082) and RBG (OR=1.434) were independently associated with type 2 diabetes in patients with AECOPD (all P>0.05). The results of logistic regression were verified and visualized by Nomogram and its-associated ccurves. The MAE and AUC curves were 0.021 and 0.847 respectively, indicating that the model had good prediction consistency and accuracy. The DCA curve showed that Nomogram's risk threshold ranged from 0.01 to 0.99, suggesting that nomogram's model had better clinical predictive value. CONCLUSION: Our results showed that increased BMI, PaCO2 and random glucose, decreased blood lymphocyte, and atrial fibrillation is an independent clinical feature of AECOPD with T2DM. These results suggest that the immune function of patients with AECOPD and T2DM are more severely impaired and more likely to be accompanied by atrial fibrillation, which is a potential cause of poor prognosis in these patients. Meanwhile, this conclusion needs to be further verified in multicenter study with large sample size.

Navafenterol is a new compound with both muscarinic receptor antagonist and β2 receptor agonist effects in a single molecule, who is being developed for the treatment of chronic obstructive airway disease such as chronic obstructive pulmonary disease and asthma. These pilot clinical studies found that it can significantly improve lung function and symptoms, and is safe and well tolerated. Common treatment emergent adverse events include headache, nasopharyngitis, and dizziness. It may become a next-generation bronchodilator for chronic obstructive airway disease. This review introduced the prospective of Navafenterol.

More than 300 million people worldwide suffer from asthma, and the incidence is increasing year by year. As one of the most common chronic diseases, asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity. With the in-depth study of physiological and pathological mechanisms, therapeutic small molecule and hormone drugs have been introduced to control and treat most patients, but about 5% - 10% of patients still suffer from various subtypes of difficult to control and treat asthma, that is, severe asthma. In the past decade, with the rapid development of bio-pharmaceutical research, protein and antibody have become the key drugs for the treatment of severe asthma with high efficacy, high specificity and high safety. However, biological drugs are usually administered by injection, they cannot be noninvasive and directly delivered into the lung to quickly absorb and take effect. Therefore, there is an urgent need for the introduction of inhaled biologics with quick effectiveness, convenience, economy and safety in clinical. The review summarizes the existing small molecule, hormone and biological therapy drugs, and summarizes the development of inhalable biological agents of asthma, and analyzes the future prospects of the inhalable biological drugs, which is designed to deepen the perception of the direction of the inhalable biological drugs research, and update the information of the field, in order to provide reference for the development of more inhalable biologics.

Severe asthma stands as a formidable contributor to both mortality and morbidity of patients suffering asthma, casting substantial social and economic shadows on communities. As our understanding of asthma's pathophysiology deepens, a beacon of hope emerges in the form of biological targeted therapies, offering a promising avenue for the management of this challenging condition. These therapies, by precisely inhibiting or modulating pivotal molecules in the inflammatory cascade, offer potential benefits in symptom alleviation, lung function enhancement, and risk reduction of acute exacerbations. They signify a paradigm shift in severe asthma treatment. Within the confines of this article, we embark on a systematic exploration of the immunological underpinnings that define severe asthma. By delving into the intricacies of the immune system's role in exacerbating this condition, we aim to offer a comprehensive assessment of both the current landscape and the future prospects of biological therapies. Our objective is to provide a scientifically robust and valuable reference that can guide the individualized treatment of patients grappling with severe asthma.

Allergen specific immunotherapy (AIT) is to identify the patient's allergen, give the patient repeated exposure to the allergen extract, and gradually increase the concentration and dose until the target maintenance dose is reached, so that the patient can develop tolerance to the allergen, which is the only treatment that can regulate the pathogenesis of allergic diseases and change its natural course. In recent years, domestic and foreign scholars have made great progress in the clinical practice and research field of AIT. This article reviewed the relevant progress of the mechanism, efficacy and drug administration of AIT.