The Global Initiative defines COPD for chronic obstructive lung disease as an entirely preventable and treatable disease characterized by sputum production, bacterial colonisation, neutrophilic bronchial airway inflammation and poor health status. The World Health Organization (WHO) estimates that COPD will become the fourth-most common cause of death worldwide, just behind ischemic heart disease, cerebrovascular disease and HIV/AIDS, by 2030. The aim of this study was to determine the main structure feature of sputum potentially pathogenic microorganisms in subjects with COPD during the clinical stable state. We employed a molecular genetics-based investigation of the bacteria community, including DNA isolation, PCR amplification and DGGE profiling. PCR-denaturing gradient gel electrophoresis (DGGE) with universal primers targeting the V3 region of the 16S rRNA gene was employed to characterize the overall COPD patient sputum microbiota composition, and some excised gel bands were cloned for sequencing. Real-time PCR was further utilized to quantitatively analyze the subpopulation of microbiota using group-specific primers targeting Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa. The DGGE profiles of two groups displayed significant differences between COPD and healthy groups (P < 0.05). Real-time PCR revealed significant increases of Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa (P < 0.05) in the COPD group compared with the healthy group. This study revealed strong relationship between alterations of sputum microbiota and COPD. By determining the content of several types of bacteria, we can provide evidence to aid in the diagnosis and treatment of COPD.

Lactobacillus rhamnosus (LBS) is a well-documented probiotic strain in oncology and has a pivotal role in clinical applications. Here, we have investigated the protective effect of Lactobacillus rhamnosus on intestinal mucositis induced by cisplatin (CP) and explored the underlying mechanisms targeting inflammatory proteins, as well as the histological changes in the intestinal tissue of mice, in addition, the bacterial strains that may be related to the health-enhancing properties. BALB/c mice were pre-treated with or without LBS via oral gavage, followed by mucositis induction with cisplatin. Our results revealed that the LBS-treated groups significantly attenuated proinflammatory cytokine levels (IL-1β, IL-6, and TNF-α) compared to the CP group. Furthermore, LBS mitigated the damaged tight junction integrity caused by CP via up-regulating the levels of claudin, occludin, ZO-1, and mucin-2 protein (MUC-2). Finally, the 16S rRNA fecal microbiome genomic analysis showed that LBS administration enhanced the growth of beneficial bacteria, i.e., Firmicutes and Lachnospiraceae, while the relative abundance of the opportunistic bacteria Bacteroides and Proteobacteria decreased. Collectively, LBS was found to beneficially modulate microbial composition structure and functions and enrich the ecological diversity in the gut.

Treating patients suffering from EGFR mutant non-small cell lung cancer (NSCLC) with first-generation EGFR tyrosine kinase inhibitors (EGFR TKI) provides excellent response rates. However, approximately 60% of all patients ultimately develop drug resistance due to a second T790M EGFR TKI mutation. In this study, we report the novel molecule N-(3-((5-chloro-2-(4-((1-morpholino)methyl)phenylamino)-4-pyrimidinyl)amino)phenyl)acrylamide (DY3002) to preferentially inhibit the EGFR T790M mutant (EGFR^T790M) (IC₅₀ = 0.71 nM) over wild-type EGFR (IC₅₀ = 448.7 nM) in kinase assays. Compared to rociletinib (SI = 21.4) and osimertinib (SI = 40.9), it significantly increased selectivity (SI = 632.0) against EGFR^T790M over wild-type EGFR. Furthermore, in cell-based tests, DY3002, with an IC₅₀ value of 0.037 μM, exhibited enhanced inhibitory potency against H1975 cells. Moreover, AO/EB and DAPI staining assays as well as flow cytometer analyses indicated that DY3002 possesses superior biological properties compared to alternatives. In addition, a rat oral glucose tolerance test revealed that treatment with high drug doses (50 mg/kg) of DY3002 did not result in hyperglycemia, suggesting a reduction of side effects in NSCLC patients will be achievable relative to established EGFR inhibitors. In summary, our findings indicate DY3002 as a promising preclinical candidate for effective treatment of patients with EGFR^T790M-mutated NSCLC.

Pulmonary hypertension (PH) has a high morbidity and mortality. Despite the existing disease-targeted therapy, most patients with PH continue to suffer from difficulty in breathing, exercise intolerance, and reduced quality of life. Recently, a large body of research results has suggested that exercise rehabilitation training (ERT) seems to be a beneficial, safe, and cost-effective treatment for patients with PH. However, knowledge gaps still exist for a uniformly accepted ERT protocol, the modality, duration, intensity, and frequency of ERT in PH. The purpose of this review is to summarise the existing research evidence and knowledge, aiming to strengthen clinicians' awareness of the application of ERT in patients with PH. PubMed databases were systematically searched for eligible studies. Twelve (12) randomised controlled trials and other important studies documenting effectiveness, safety, and adverse events of ERT are summarised. Additionally, the modality, duration, intensity, and frequency of various types of ERT and future research directions are discussed. In summary, ERT is generally effective and safe for PH patients as an adjuvant treatment to disease-specific therapy. It can improve the exercise capacity and tolerance, skeletal and respiratory muscle performance, cardiopulmonary function, and quality of life of PH patients. In view of the occurrence of a small number of adverse events, we currently recommend a combination of in-hospital and home-based ERT under close supervision. In the future, more multi-centre randomised controlled studies are needed to evaluate the effectiveness and feasibility of long-term, community, or home-based ERT, as well as to explore the molecular mechanism behind it.