Emerging studies have reported the mechanosensitive Piezo1 (piezo type mechanosensitive ion channel component 1) plays essential roles in regulating the vascular tone through mechanistic actions on intracellular calcium homeostasis. However, the specific roles of Piezo1 in pulmonary vessels remain incompletely understood. We aim to investigate whether and how Piezo1 regulates the intracellular calcium homeostasis in human pulmonary arterial smooth muscle cells (PASMCs) under normal and pulmonary arterial hypertension (PAH) conditions. Cultured human PASMCs isolated from both control donors and idiopathic PAH patients were used as cell models. Fura-2 based intracellular calcium imaging was performed to measure the intracellular free calcium concentration ([Ca
2+
]
i
). Results showed that activation of Piezo1 by Yoda1 increases [Ca
2+
]
i
by inducing both intracellular calcium release from internal calcium stores through the intracellular (intra-) Piezo1 localized at the subcellular organelles, including endoplasmic reticulum/sarcoplasmic reticulum, mitochondria, and nucleus; as well as extracellular calcium influx through the plasma membrane-localized Piezo1 in a mechanism independent of the store-operated calcium entry. Moreover, the Piezo1-mediated increase of [Ca
2+
]
i
is linked to increased contraction and proliferation of PASMCs. Yoda1 induces dose-dependent vasocontraction in endothelium-denuded rat intrapulmonary arteries. Significant upregulation and increased activity of Piezo1 were observed in idiopathic PAH-PASMCs versus donor-PASMCs, contributing to the increased [Ca
2+
]
i
and excessive proliferation of idiopathic PAH-PASMCs. In summary, Piezo1 mediates the increase of [Ca
2+
]
i
by triggering both intracellular calcium release and extracellular influx. The enhanced Piezo1 expression and activity accounts, at least partially, for the abnormally elevated [Ca
2+
]
i
and proliferation in idiopathic PAH-PASMCs.
Alteration in microbiota composition of respiratory tract has been reported in the progression of many chronic lung diseases, yet, the correlation and causal link between respiratory tract microbiota and the disease development of pulmonary hypertension (PH) remain largely unknown. This study aims to define and compare the respiratory microbiota composition in pharyngeal swab samples between patients with PH and reference subjects. A total of 118 patients with PH and 79 reference subjects were recruited, and the pharyngeal swab samples were collected to sequence the 16S ribosomal RNA (16S rRNA) V3-V4 region of respiratory microbiome. The relative abundances in patients with PH were profoundly different from reference subjects. The Ace and Sobs indexes indicated that the microbiota richness of pharynx value is significantly higher; while the community diversity value is markedly lower in patients with PH, comparing to those of the reference subjects. The microbiota on pharynx showed a different profile between the 2 groups by principal component analysis. The linear discriminant analysis effect size also revealed a significantly higher proportion of Streptococcus, Lautropia, and Ralstonia in patients with PH than reference subjects. The linear discriminant analysis effect size output, which represents the microbial gene functions, suggest genes related to bacterial invasion of epithelial cells, bacterial toxins were enhanced, while genes related to energy metabolism, protein digestion and absorption, and cell division pathways were attenuated in patients with PH versus reference subjects. In summary, our study reports the first systematic definition and divergent profile of the upper respiratory tract microbiota between patients with PH and reference subjects.
Background: Hemoptysis is the most frequently reported complication of ultrasound-guided transthoracic needle lung biopsy (US-TTLB). However, factors influencing the occurrence of hemoptysis as a result of US-TTLB remain uncertain. Therefore, the aim of this study was to evaluate the incidence of hemoptysis as a complication of US-TTLB and to identify the related risk factors.
Methods:We retrospectively analyzed all data of patients who underwent US-TTLB from February 2013 through December 2016. The incidence, severity, and treatment of hemoptysis in each case were carefully recorded. Study variables were classified into patient-related factors (age, sex, smoking history, pulse oxygen saturation, laboratory tests and emphysema), biopsy-related factors (use of contrast agent, number of punctures and operators), and lesion-related factors (lesion location, size, pathology, length of puncture path and the grade of air bronchial sign). Univariate and multivariate logistic regression analyses were performed to analyze the risk factors of hemoptysis. We investigated whether incidence of hemoptysis increased according to increased grade of air bronchial sign by Mantel-Haenszel test.Results: A total of 209 patients were evaluated. Hemoptysis occurred in 20 of the 209 patients (9.6%). In univariate analysis, the lesion pathology (P=0.037) and grade of air bronchial sign (P<0.001) were statistically significant factors between the hemoptysis group and the non-hemoptysis group. In multivariate analysis, the presence of multi-air bronchogram in sonographic image (odds ratio =8.946; 95% confidence interval: 2.873-27.863; P<0.001) was a statistically significant predictive risk factor for hemoptysis complicating US-TTLB. There was a significant tendency for incidence of hemoptysis with the grade of air bronchial sign (P<0.001).
Conclusions:We found that the rate of hemoptysis complicating US-TTLB was 9.6% and the severity of hemoptysis was not serious. Target lesion without air bronchogram is a safety sign, minor bronchogram means relatively low-risk, while multiple bronchogram is a highly dangerous ultrasound sign of hemoptysis.
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