T2T-YAO: A Telomere-to-telomere Assembled Diploid Reference Genome for Han Chinese.

Since its initial release in 2001, the human reference genome has undergone continuous improvement in quality, and the recently released telomere-to-telomere (T2T) version - T2T-CHM13 - reaches its highest level of continuity and accuracy after 20 years of effort by working on a simplified, nearly homozygous genome of a hydatidiform mole cell line. Here, to provide an authentic complete diploid human genome reference for the Han Chinese, the largest population in the world, we assembled the genome of a male Han Chinese individual, T2T-YAO, which includes T2T assemblies of all the 22 + X + M and 22 + Y chromosomes in both haploid. The quality of T2T-YAO is much better than all currently available diploid assemblies, and its haploid version, T2T-YAO-hp, generated by selecting the better assembly for each autosome, reaches the top quality of fewer than one error per 29.5 Mb, even higher than that of T2T-CHM13. Derived from an individual living in the aboriginal region of the Han population, T2T-YAO shows clear ancestry and potential genetic continuity from the ancient ancestors. Each haplotype of T2T-YAO possesses ∼ 330-Mb exclusive sequences, ∼ 3100 unique genes, and tens of thousands of nucleotide and structural variations as compared with CHM13, highlighting the necessity of a population-stratified reference genome. The construction of T2T-YAO, a truly accurate and authentic representative of the Chinese population, would enable precise delineation of genomic variations and advance our understandings in the hereditability of diseases and phenotypes, especially within the context of the unique variations of the Chinese population.

The Difference in All-Cause Mortality Between Allergic Bronchopulmonary Aspergillosis with and without Chronic Obstructive Pulmonary Disease.

Background: Allergic bronchopulmonary aspergillosis (ABPA) primarily complicates the course of asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). Mortality data of ABPA and the difference in all-cause mortality between ABPA with and without COPD are not available. Objective: We investigated the difference in all-cause mortality between ABPA with and without COPD. Methods: A retrospective review was performed among patients with the diagnosis of ABPA at Peking University People's Hospital between January 2010 and March 2022. Logrank test was performed to investigate the difference between all-cause mortality for ABPA with and without COPD and Cox regression analysis was performed to investigate the independent risk factors for all-cause mortality in patients with ABPA. Results: Sixty-one patients with ABPA were enrolled in this study. The follow-up duration was 50.38 months (3-143 months). In the COPD group, 7 patients died (7/10), while in the non-COPD group, 4 patients died (4/51). The 1-year survival rates of ABPA with and without COPD were 60% and 97.8%, respectively. The 5-year survival rates of ABPA with and without COPD were 40% and 94%, respectively. The Cox regression analysis showed that higher C-reactive protein (CRP) (HR = 1.017, 95% CI 1.004-1.031, P = 0.013) and complicating COPD (HR = 8.525, 95% CI 1.827-39.773, P = 0.006) were independent risk factors associated with mortality in patients with ABPA. Conclusion: The all-cause mortality for ABPA with COPD is higher than that for ABPA without COPD. Higher CRP and complicating COPD are independent risk factor for mortality in patients with ABPA.

A Novel c-Mesenchymal-Epithelial Transition Factor Intergenic Fusion Response to Crizotinib in a Chinese Patient With Lung Adenocarcinoma: A Case Report.

BACKGROUND: The c-mesenchymal-epithelial transition factor (C-MET) is an oncogene encoding a tyrosine kinase receptor that plays an important role in tumor growth and metastasis. The National Comprehensive Cancer Network (NCCN) guidelines have approved carbatinib/crizotinib for advanced non-small cell lung cancer (NSCLC) patients with MET exon 14 skipping. METHODS: In June 2020, the Department of Respiratory and Critical Care Medicine of Peking University People's Hospital admitted a 72-year-old male patient with lung adenocarcinoma (LADC) with a history of interstitial lung disease secondary to antineutrophil cytoplasmic antibody-associated vasculitis. Genetic examination by next-generation sequencing showed an intergenic fusion of MET, and crizotinib was administered on August 14, 2020. Follow-up showed that tumor volume was significantly reduced. However, crizotinib was discontinued in November 2020 because of the patient's worsening interstitial lung disease, and CT scans showed continued partial response (PR) for 5 months. In April 2021, right lower lobe mass progressed, and disease progression was considered. CONCLUSION: This was the first case of a patient with LADC with MET intergenic fusion who significantly benefited from crizotinib. Even after crizotinib was discontinued for 5 months, the patient continued exhibiting PR, suggesting that MET intergenic fusion may have carcinogenic activity in LADC and was sensitive to crizotinib.

Macrolide therapy decreases chronic obstructive pulmonary disease exacerbation: a meta-analysis.

BACKGROUND: Macrolide antibiotics have anti-inflammatory effects, and long-term administration may reduce chronic obstructive pulmonary disease (COPD) exacerbations. OBJECTIVE: To investigate the effects of long-term treatment of macrolide therapy for COPD. METHODS: We searched the PubMed and Embase databases to identify randomized controlled trials that evaluated the effect of macrolide therapy (of at least 2 weeks) for COPD. The primary outcome assessed was the frequency of acute exacerbations during follow-up. RESULTS: Six trials involving 1,485 COPD patients were included in the analysis. Analysis of the pooled data of all 6 trials showed that macrolide administration reduced the frequency of acute exacerbations of COPD [risk ratio (RR) = 0.62; 95% CI 0.43-0.89, p = 0.01]. Subgroup analysis showed that only erythromycin might be associated with decreased COPD exacerbations (erythromycin: p = 0.04, azithromycin: p = 0.22, clarithromycin: p = 0.18). Moreover, macrolide therapy for 3 months did not significantly reduce the number of exacerbations (p = 0.18), whereas a beneficial effect was conclusive in the 6-month (p = 0.009) and 12-month (p = 0.03) treatment subgroups. In addition, nonfatal adverse events were more frequent in the macrolide treatment groups than in the controls (RR = 1.32; 95% CI 1.06-1.64, p = 0.01). However, related clinical factors had no influence on the overall result (p = 0.19). There was no publication bias among the included trials. CONCLUSIONS: Macrolide therapy was effective and safe in decreasing the frequency of exacerbations in patients with COPD. Treatment might provide a significant benefit but only when therapy lasts more than 6 months.