Clinical characteristics of patients with non-tuberculous mycobacterial pulmonary disease: a seven-year follow-up study conducted in a certain tertiary hospital in Beijing.

Background: The incidence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) has increased in recent years. However, the clinical and immunologic characteristics of NTM-PD patients have received little attention. Methods: NTM strains, clinical symptoms, underlying diseases, lung CT findings, lymphocyte subsets, and drug susceptibility tests (DSTs) of NTM-PD patients were investigated. Then, the counts of immune cells of NTM-PD patients and their correlation were evaluated using principal component analysis (PCA) and correlation analysis. Results: 135 NTM-PD patients and 30 healthy controls (HCs) were enrolled from 2015 to 2021 in a certain tertiary hospital in Beijing. The number of NTM-PD patients increased every year, and Mycobacterium intracellulare (M. intracellulare), M. abscessus, M. avium, and M. kansasii were the major pathogens of NTM-PD. The main clinical symptoms of NTM-PD patients were cough and sputum production, and the primary lung CT findings were thin-walled cavity, bronchiectasis, and nodules. In addition, we identified 23 clinical isolates from 87 NTM-PD patients with strain records. The DST showed that almost all of M. abscessus and M. avium and more than half of the M. intracellulare and M. avium complex groups were resistant to anti-tuberculosis drugs tested in this study. M. xenopi was resistant to all aminoglycosides. M. kansasii was 100% resistant to kanamycin, capreomycin, amikacin, and para-aminosalicylic acid, and sensitive to streptomycin, ethambutol, levofloxacin, azithromycin, and rifamycin. Compared to other drugs, low resistance to rifabutin and azithromycin was observed among NTM-PD isolates. Furthermore, the absolute counts of innate and adaptive immune cells in NTM-PD patients were significantly lower than those in HCs. PCA and correlation analysis revealed that total T, CD4+, and CD8+ T lymphocytes played an essential role in the protective immunity of NTM-PD patients, and there was a robust positive correlation between them. Conclusion: The incidence of NTM-PD increased annually in Beijing. Individuals with bronchiectasis and COPD have been shown to be highly susceptible to NTM-PD. NTM-PD patients is characterized by compromised immune function, non-specific clinical symptoms, high drug resistance, thin-walled cavity damage on imaging, as well as significantly reduced numbers of both innate and adaptive immune cells.

Effects of Buyang Huanwu Decoction on Intestinal Barrier, Intestinal Flora, and Trimethylamine Oxide in Rats with Heart Failure.

OBJECTIVE: To explore the mechanisms of Buyang Huanwu Decoction (BYHWD) modulating the gut microbiome and trimethylamine oxide (TAMO) to exert cardioprotective effects. METHODS: Ligation of the left anterior descending coronary artery was performed in rats to induce heart failure (HF). Except for the sham-operation group (n=10), 36 operation-induced models were randomized into 3 groups using a random number table (n=12 in each group): the model group, the BYHWD group (15.02 g/kg BYHWD), and the positive group (4.99 g/kg metoprolol succinate). After 4-week treatment (once daily by gavage), echocardiography was applied to evaluate the cardiac function and the Tei index (the ratio of ventricular isovolumic contraction time (IVCT) and isovolumic diastolic time (IVRT) to ejection time (ET)) was calculated; hematoxylin-eosin (HE) staining was observed to characterize the pathology of the myocardium and small intestinal villi. D-lactic acid was detected by an enzyme-linked immunosorbent assay (ELISA). Expressions of occludin, claudin-1, and zonula occludens (ZO-1) were detected by Western blot. 16S ribosomal ribonucleic acid (16S rRNA) sequencing was used to explore the changes in the intestinal flora. TMAO was detected via liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: In the echocardiography, the Tei index was considerably lower in the positive and BYHWD groups compared with the model group (P<0.05). Besides, BYHWD improved the pathology of myocardium and small intestine of HF rats and lowered the D-lactic acid content in the serum, when compared with the model group (P<0.05). BYHWD also improved the expression of occludin and claudin-1 (P<0.05); in the gut microbiota analysis, BYHWD slowed down modifications in the structure distribution of gut microbiota and regulated the diversity of intestinal flora in HF rats. The content of TMAO in the serum was significantly lowered by BYWHT compared with the model group (P<0.05). CONCLUSION: BYHWD may delay progression of HF by enhancing the intestinal barrier structure, and regulating intestinal flora and TAMO.

The Effect and Mechanism of Chinese Herbal Formula Sini Tang in Heart Failure after Myocardial Infarction in Rats.

OBJECTIVE: To investigate the effectiveness and mechanism of the Chinese herbal formula Sini Tang (SNT) which consists of Aconitum carmichaelii (Fuzi), Zingiber officinale (Gan Jiang), and Glycyrrhiza uralensis (Gancao) in heart failure after myocardial infarction in rats. METHODS: We established the heart failure after myocardial infarction in model of SD rats by ligating the anterior descending branch of left coronary artery. Rats were randomly divided into six experimental groups: Sham operation group, HF group, Benazepril group, high dose of SNT group, medium dose of SNT group, and low dose of SNT group. Drugs were administered by oral gavage for eight weeks. The detection indexes include left ventricular function by echocardiogram, Collagen Volume Fraction by Masson staining, level of Plasma Renin, Angiotensin II and Aldosterone by radioimmunoassay, protein and gene level of ACE and AT1R by western-blot, and real-time PCR. RESULTS: The outcomes of this study indicated that SNT significantly improved the LVEF and LVFS, thickened both LVAWd and LVAWs, and reduced LVIDs in heart failure after myocardial infarction in rats when compared with control group (P < 0.05). Besides, SNT significantly reduced the Collagen Volume Fraction (P < 0.05). The results of radioimmunoassay showed that SNT decreased the level of Plasma Renin, Angiotensin II, and Aldosterone (P < 0.05). The outcomes of western-blot and real-time PCR analysis showed that SNT significantly downregulated the protein and gene level of ACE and AT1R (P < 0.05). CONCLUSIONS: The Chinese herbal formula SNT could improve left ventricular systolic function in heart failure after myocardial infarction in rats and decreased the level of Plasma Renin, Angiotensin II, and Aldosterone, as well as downregulating the protein and gene level of ACE and AT1R. Therefore, SNT has potential benefits of improving cardiac function by inhibiting the excessive activation of Renin-Angiotensin-Aldosterone system in heart failure after myocardial infarction in rats.