Genetic Variants in <i>MUC4</i> Gene Are Associated with Lung Cancer Risk in a Chinese Population

<div><p>Mucin MUC4, which is encoded by the <i>MUC4</i> gene, plays an important role in epithelial cell proliferation and differentiation. Aberrant <i>MUC4</i> overexpression is associated with invasive tumor proliferation and poor outcome in epithelial cancers. Collectively, the existing evidence suggests that <i>MUC4</i> has tumor-promoter functions. In this study, we performed a case-control study of 1,048 incident lung cancer cases and 1,048 age- and sex frequency-matched cancer-free controls in a Chinese population to investigate the role of <i>MUC4</i> gene polymorphism in lung cancer etiology. We identified nine SNPs that were significantly associated with increased lung cancer risk (<i>P</i> = 0.0425 for rs863582, <i>0.0333</i> for rs842226, <i>0.0294</i> for rs842225, <i>0.0010</i> for rs2550236, <i>0.0149</i> for rs2688515, <i>0.0191</i> for rs 2641773, <i>0.0058</i> for rs3096337, <i>0.0077</i> for rs859769, and <i>0.0059</i> for rs842461 in an additive model). Consistent with these single-locus analysis results, the haplotype analyses revealed an adverse effect of the haplotype “GGC” of rs3096337, rs859769, and rs842461 on lung cancer. Both the haplotype and diplotype “CTGAGC” of rs863582, rs842226, rs2550236, rs842225, and rs2688515 had an adverse effect on lung cancer, which is also consistent with the single-locus analysis. Moreover, we observed statistically significant interactions for rs863582 and rs842461 in heavy smokers. Our results suggest that <i>MUC4</i> gene polymorphisms and their interaction with smoking may contribute to lung cancer etiology. </p> </div

Author_response_to_reviewers – Supplemental material for The efficacy of adding budesonide/formoterol to ipratropium plus theophylline in managing severe chronic obstructive pulmonary disease: an open-label, randomized study in China

Supplemental material, Author_response_to_reviewers for The efficacy of adding budesonide/formoterol to ipratropium plus theophylline in managing severe chronic obstructive pulmonary disease: an open-label, randomized study in China by Kewu Huang, Yanfei Guo, Jian Kang, Li An, Zeguang Zheng, Lijun Ma, Liping Peng, Hongyang Wang, Rong Su, Yohji Itoh and Chen Wang in Therapeutic Advances in Respiratory Disease</p

Reviewer_1_v.1 – Supplemental material for The efficacy of adding budesonide/formoterol to ipratropium plus theophylline in managing severe chronic obstructive pulmonary disease: an open-label, randomized study in China

Supplemental material, Reviewer_1_v.1 for The efficacy of adding budesonide/formoterol to ipratropium plus theophylline in managing severe chronic obstructive pulmonary disease: an open-label, randomized study in China by Kewu Huang, Yanfei Guo, Jian Kang, Li An, Zeguang Zheng, Lijun Ma, Liping Peng, Hongyang Wang, Rong Su, Yohji Itoh and Chen Wang in Therapeutic Advances in Respiratory Disease</p

Reviewer_2_v.1 – Supplemental material for The efficacy of adding budesonide/formoterol to ipratropium plus theophylline in managing severe chronic obstructive pulmonary disease: an open-label, randomized study in China

Supplemental material, Reviewer_2_v.1 for The efficacy of adding budesonide/formoterol to ipratropium plus theophylline in managing severe chronic obstructive pulmonary disease: an open-label, randomized study in China by Kewu Huang, Yanfei Guo, Jian Kang, Li An, Zeguang Zheng, Lijun Ma, Liping Peng, Hongyang Wang, Rong Su, Yohji Itoh and Chen Wang in Therapeutic Advances in Respiratory Disease</p

Graphical representation of the SNP locations and LD structure of nine genotyped SNPs of <i>MUC4</i> in 1,048 southern Han Chinese controls.

<p>The exact SNP positions are listed in Table 1. Two haplotype blocks (colored) were defined by the Haploview program using the approach described by Gabriel et al. ^[34] with default settings (the 95% CI for a strong LD was minimal for upper 0.98 and low 0.7, and maximal for a strong recombination of 0.9, and a fraction of strong LD in informative comparisons was at least 0.95). The rs number (top, from right to left) corresponds to the SNP name, and the numbers in squares are D' values (|D'|×100). The measure of LD (D') among all possible pairs of SNPs is shown graphically according to red shading, where white represents very low D', and dark red represents very high D'.</p

Reviewer_1_v.2 – Supplemental material for The efficacy of adding budesonide/formoterol to ipratropium plus theophylline in managing severe chronic obstructive pulmonary disease: an open-label, randomized study in China

Supplemental material, Reviewer_1_v.2 for The efficacy of adding budesonide/formoterol to ipratropium plus theophylline in managing severe chronic obstructive pulmonary disease: an open-label, randomized study in China by Kewu Huang, Yanfei Guo, Jian Kang, Li An, Zeguang Zheng, Lijun Ma, Liping Peng, Hongyang Wang, Rong Su, Yohji Itoh and Chen Wang in Therapeutic Advances in Respiratory Disease</p

Additional file 1 of Effect of hydrogen/oxygen therapy for ordinary COVID-19 patients: a propensity-score matched case-control study

Supplementary Material

Data_Sheet_1_Evaluation of safety and efficacy of inhaled ambroxol in hospitalized adult patients with mucopurulent sputum and expectoration difficulty.docx

BackgroundAmbroxol is a widely used mucoactive drug in sputum clearance of respiratory diseases taken orally and by injection. However, there is a paucity of evidence for inhaled ambroxol in sputum clearance.MethodsThis study performed a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial at 19 centers in China. Hospitalized adult patients with mucopurulent sputum and expectoration difficulty were recruited. Patients were randomized by 1:1 to receive inhalation of either ambroxol hydrochloride solution 3 mL (22.5 mg) + 0.9% sodium chloride 3 mL or 0.9% sodium chloride 6 mL twice daily for 5 days, with an interval of more than 6 h. The primary efficacy endpoint was the absolute change in the sputum property score after treatment compared to the baseline in the intention-to-treat population.ResultsBetween 10 April 2018 and 23 November 2020, 316 patients were recruited and assessed for eligibility, of whom 138 who received inhaled ambroxol and 134 who received a placebo were included. Patients who received inhaled ambroxol had a significantly greater decrease in the sputum property score compared with patients who received inhalation of placebo (difference: −0.29; 95% CI: −0.53 to −0.05; p = 0.0215). Compared with the placebo, inhaled ambroxol also significantly reduced more expectoration volume in 24 h (difference: −0.18; 95% CI: −0.34 to −0.03; p  = 0.0166). There was no significant difference in the proportion of adverse events between the two groups, and no deaths were reported.DiscussionIn hospitalized adult patients with mucopurulent sputum and expectoration difficulty, inhaled ambroxol was safe and effective for sputum clearance compared with a placebo.Clinical trial registration[https://www.chictr.org.cn/showproj.html?proj=184677], Chinese Clinical Trial Registry [ChiCTR2200066348].</p