Objective:To investigate off-label drug use and the incidence of adverse events (AE) in patients with nontuberculous mycobacterial (NTM) pulmonary disease, and to provide reference in standardization of off-label drug use in this population.Methods:The medical records of NTM pulmonary disease patients in our hospital from January to December 2024 were retrieved based on the presence of "nontuberculous mycobacteria" in the diagnosis. The demographic characteristics of patients (gender, age), underlying diseases, identified NTM species, details of off-label prescribing (clinical medication indications and the name, duration and frequency of drugs), and the AE occurrence were collected. The utilization rate, AE incidence, and off-label use rate of the anti-NTM drugs were calculated.Results:A total of 259 patients with NTM pulmonary disease were included in the analysis, including 125 males and 134 females, aged (61±11) years with a range of 20-83 years; 243 patients (93.8%) were complicated with underlying diseases, 99 cases (38.2%) of which had 2 or more underlying diseases. Among the 259 patients, the top 3 pathogenic bacteria in the sputum and bronchoalveolar lavage fluid were Mycobacterium intracellulare (126 cases, 48.6%), Mycobacterium abscessus (50 cases, 19.3%), and Mycobacterium avium (30 cases, 11.6%); 16 patients (6.2%) were co-infected with 2 strains. All of the 259 patients were treated with a combination therapy of 4 drugs without discontinuation at least 1 year after the negative sputum culture. All 259 patients had off-label drug use, mainly including off-label indication [98.8%(256/259)] and prolonged treatment duration(100%). Among the 259 patients, 17 kinds of off-label drugs were involved, and the top 5 in terms of usage frequency were ethambutol (182 cases, 70.3%), amikacin (141 cases, 54.4%), azithromycin (140 cases, 54.1%), clarithromycin (135 cases, 52.1%), and rifabutin (106 cases, 40.9%). The overall AE incidence was 37.5% (97/259), mainly including gastrointestinal reactions [17.4% (45/259)], skin pruritus [12.0% (31/259)], and abnormal liver function [9.7% (25/259)]. The incidences of severe AE and AE involving 2 or more systems were 5.0% (13/259) and 17.4% (45/259), respectively. Conclusions:Off-label drug use is prevalent in patients with NTM pulmonary disease, mainly characterized by off-label indications and prolonged treatment duration. A variety of drugs are involved, among which ethambutol, amikacin, macrolides, and rifabutin are the most common. The types of AE reported are all common, mainly including gastrointestinal reactions, allergic reactions, and abnormal liver function, with a low proportion of severe AE. However, off-label use carries inherent risks, it is necessary to strengthen therapeutic drug monitoring and management during the treatment of NTM pulmonary disease.

Objective:To investigate off-label drug use and the incidence of adverse events (AE) in patients with nontuberculous mycobacterial (NTM) pulmonary disease, and to provide reference in standardization of off-label drug use in this population.Methods:The medical records of NTM pulmonary disease patients in our hospital from January to December 2024 were retrieved based on the presence of "nontuberculous mycobacteria" in the diagnosis. The demographic characteristics of patients (gender, age), underlying diseases, identified NTM species, details of off-label prescribing (clinical medication indications and the name, duration and frequency of drugs), and the AE occurrence were collected. The utilization rate, AE incidence, and off-label use rate of the anti-NTM drugs were calculated.Results:A total of 259 patients with NTM pulmonary disease were included in the analysis, including 125 males and 134 females, aged (61±11) years with a range of 20-83 years; 243 patients (93.8%) were complicated with underlying diseases, 99 cases (38.2%) of which had 2 or more underlying diseases. Among the 259 patients, the top 3 pathogenic bacteria in the sputum and bronchoalveolar lavage fluid were Mycobacterium intracellulare (126 cases, 48.6%), Mycobacterium abscessus (50 cases, 19.3%), and Mycobacterium avium (30 cases, 11.6%); 16 patients (6.2%) were co-infected with 2 strains. All of the 259 patients were treated with a combination therapy of 4 drugs without discontinuation at least 1 year after the negative sputum culture. All 259 patients had off-label drug use, mainly including off-label indication [98.8%(256/259)] and prolonged treatment duration(100%). Among the 259 patients, 17 kinds of off-label drugs were involved, and the top 5 in terms of usage frequency were ethambutol (182 cases, 70.3%), amikacin (141 cases, 54.4%), azithromycin (140 cases, 54.1%), clarithromycin (135 cases, 52.1%), and rifabutin (106 cases, 40.9%). The overall AE incidence was 37.5% (97/259), mainly including gastrointestinal reactions [17.4% (45/259)], skin pruritus [12.0% (31/259)], and abnormal liver function [9.7% (25/259)]. The incidences of severe AE and AE involving 2 or more systems were 5.0% (13/259) and 17.4% (45/259), respectively. Conclusions:Off-label drug use is prevalent in patients with NTM pulmonary disease, mainly characterized by off-label indications and prolonged treatment duration. A variety of drugs are involved, among which ethambutol, amikacin, macrolides, and rifabutin are the most common. The types of AE reported are all common, mainly including gastrointestinal reactions, allergic reactions, and abnormal liver function, with a low proportion of severe AE. However, off-label use carries inherent risks, it is necessary to strengthen therapeutic drug monitoring and management during the treatment of NTM pulmonary disease.

Objective To investigate the effect of Ba Bao Dan(BBD)on cardiac injury induced by doxorubicin in zebrafish.Methods We induced a zebrafish myocardial injury model using the chemotherapeutic drug,doxorubicin.We then examined the effects of different concentrations of BBD on pericardial edema and heart rate under an in vivo microscope.We also examined the inhibitory effects of BBD on neutrophil infiltration in the heart in Tg(mpx:EGFP)transgenic zebrafish.The impacts of BBD on superoxide dismutase,catalase,and malondialdehyde were observed.mRNA expression levels of ferroptosis-related factors,including glutathione peroxidase 4a(gpx4a),prostaglandin-endoperoxide synthase 2(ptgs2),arachidonate 5-lipoxygenase(alox5a),and acyl-CoA synthetase long-chain family member 4(acsl4)were determined by Real-time quantitative polymerase chain reaction.The accumulation of ferrous ions in zebrafish heart was assessed using a fluorescent probe for ferrous ions.Results BBD alleviated doxorubicin-induced pericardial edema and bradycardia in zebrafish,reduced neutrophil infiltration in the heart(P＜0.05),decreased malondialdehyde concentration(P＜0.05),and enhanced the activities of superoxide dismutase and catalase(P＜0.05).BBD also significantly inhibited ferroptosis,reduced the accumulation of ferrous ions in the zebrafish heart,suppressed the expression of ptgs2,alox5a,and acsl4(P＜0.05),and promoted the expression of gpx4a(P＜0.05).Conclusions BBD can attenuate doxorubicin-induced zebrafish myocardial injury and improve cardiac function by inhibiting lipid peroxidation and regulating ferroptosis.

Yarrowia lipolytica is a non-conventional yeast with unique physiological and metabolic characteristics. It is suitable for production of various products due to its natural ability to utilize a variety of inexpensive carbon sources, excellent tolerance to low pH, and strong ability to secrete metabolites. Currently, Y. lipolytica has been demonstrated to produce a wide range of carboxylic acids with high efficiency. This article summarized the progress in engineering Y. lipolytica to produce various carboxylic acids by using metabolic engineering and synthetic biology approaches. The current bottlenecks and solutions for high-level production of carboxylic acids by engineered Y. lipolytica were also discussed, with the aim to provide useful information for relevant studies in this field.
Carboxylic Acids/metabolism* ; Metabolic Engineering ; Synthetic Biology ; Yarrowia/metabolism*