Heterozygous SOD2 deletion deteriorated chronic intermittent hypoxia-induced lung inflammation and vascular remodeling through mtROS-NLRP3 signaling pathway.

Oxidative stress caused by chronic intermittent hypoxia (CIH) is the hallmark of obstructive sleep apnea (OSA). Among the first line of defense against oxidative stress is the dismutation of superoxide radicals, which in the mitochondria is carried out by manganese superoxide dismutase (SOD2). In this study, wild-type (WT) and SOD2-heterozygous knockout (SOD2+/-) mice were exposed to CIH or normoxic (Nor) conditions. After 4 weeks, pulmonary artery pressure was measured, and the mice were processed to harvest either serum for cytokine assays or lungs for flow cytometry and histopathological studies. Herein, we showed that heterozygous deletion of SOD2 markedly deteriorated pulmonary remodeling and increased the oxidative stress, especially promoted the infiltration of macrophages in the lungs of CIH mouse. Moreover, in the intermittent hypoxia (IH)-treated RAW264.7 cells, SOD2 knockdown increased the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation accompanied with the IL-1ß elevation and caspase-1 activity. Additionally, mitochondrial ROS (mtROS) scavenger mito-TEMPO abolished NLRP3 inflammasome activation in IH-treated RAW264.7 cells. Collectively, our results supported that SOD2 contributed to the pathogenesis of CIH-induced lung remodeling. Meanwhile, SOD2 knockdown exacerbates oxidative damage through assembly and activation of NLRP3 inflammasome in macrophages. SOD2 may be a novel therapeutic target for CIH-induced pulmonary inflammation and arteriole remodeling.

Evaluation of conventional TBNA needle aspiration smear and embedding in the diagnosis of central airway peripheral lesions / 中国内镜杂志

Objective To evaluate the yield of conventional transbronchial needle aspiration (C-TBNA) in the diagnosis of patients with central airway peripheral lesions. Methods This was a retrospective study, 77 patients with central airway peripheral lesions were enrolled from January 2011 to March 2017. Specimens were smeared and/or embedded. Results The positive diagnostic value for malignant lesions were 92.86% (52/56), and 42.86%(9/21) for benign lesions. The average value was 79.22% (61/77). Conclusions C-TBNA had high positive rate of diagnosis and less complications for cent ral airway peripheral lesions.

[Effect of moxibustion of "dachangshu" (BL 25) area on pain reaction and TRPV 1 mRNA expression of bone marrow cells in visceral hyperalgesia rats].

OBJECTIVE: To observe the effect of moxibustion of "Dachangshu" (BL 25) on pain reaction and expression of transient receptor potential vanilloid 1 (TRPV 1) of bone marrow cells in visceral hyperalgesia (VHA) rats so as to explore its mechanism underlying visceral pain-relief. METHODS: Twenty-eight male SD rats were divided into control group, control+moxibustion group, VHA model and VHA+moxibustion group (n = 7/group). The VHA model was made by giving colorectal distension (CRD, 60 mmHg) to the newborn rats for 1 min (repeated once again in 30 min) from postnatal day 8 on, once daily for a week. Moxibustion was applied to ipsilateral "Dachangshu"(BL 25) area for 40 min from the 8th week on after birth. Abdominal withdrawal reflex (AWR) and pain threshold during CRD were measured before and after moxibustion. The TRPV 1 mRNA expressio of bone marrow cells was detected by real time-POR. RESULTS: (1) The AWR score of the model group was significantly higher than that of the control group, but the pain threshold of the model group was significantly lower than that of the control group (P < 0.01), suggesting a VHA in model rats. (2) After moxibustion, the AWR scores were significantly lower in the VHA+moxibustion group than in the model group (P < 0.05, P < 0.01), and the pain threshold was remarkably higher in the former group than in the latter group (P < 0.01). Similar results were found in the control+moxibustion group compared to the control group: the decreased AWR scores (CRD 40 mmHg, 60 mmHg and 80 mmHg, P < 0.01) and the increased pain threshold (P < 0.05). (3) The TRPV 1 mRNA expression level of bone marrow cells was significantly lower in the VHA + moxibustion group than in the model group (P < 0.01). No significant difference was found between the control and moxibustion+control groups in TRPV 1 mRNA expression level (P > 0.05). CONCLUSION: Moxibustion of "Dachangshu" (BL 25) can reduce visceral hyperalgesia and down-regulate TRPV 1 mRNA expression of bone marrow cells in VHA rats, suggesting an involvement of TRPV 1 mRNA of bone marrow cells in CRD-induced visceral pain development.

[Comparison of peripheral blood hematopoietic progenitor cells among patients with paroxysmal, permanent atrial fibrillation or sinus rhythm].

OBJECTIVE: To compare peripheral blood hematopoietic progenitor cells (HPCs), plasma atrial natriuretic peptide (ANP) and stromal cell-derived factor-1alpha (SDF-1alpha) among patients with paroxysmal, permanent atrial fibrillation (AF) or sinus rhythm. METHODS: Peripheral blood concentration of CD34+HPCs were quantified by flow cytometric analysis (FCM), plasma ANP levels were measured by radioimmunoassay (RIA) method, plasma levels of SDF-1alpha were determined by enzyme linked immunosorbent assay (ELISA) in 30 patients with permanent AF, 28 patients with paroxysmal AF, and 30 patients with sinus rhythm (SR). HPCs were separated, cultured and stained for ANP by the use of alkaline phosphatase-anti-alkaline phosphatase technique (APAAP) in 30 patients (10 from each group). RESULTS: (1) The number of CD34+HPCs in permanent AF group [(5.31 +/- 1.67) x 10(6)/L] were significantly higher comparing to paroxysmal AF group [(2.33 +/- 1.29) x 10(6)/L] (P < 0.05) and SR group [(2.03 +/- 0.64) x 10(6)/L] (P < 0.05) while CD34+HPCs was similar between paroxysmal AF group and SR group (P > 0.05). (2) Plasma levels of ANP (0.312 +/- 0.121) microg/L and SDF-1alpha (3210.2 +/- 1234.7) ng/L were also significantly higher in permanent AF group than paroxysmal AF group and SR group (all P < 0.05) and were similar in paroxysmal AF group and SR group (all P > 0.05). (3) The plasma levels of ANP and SDF-1alpha were both positive correlated with peripheral blood concentration of CD34+HPCs (r = 0.783, P < 0.01; r = 0.427, P < 0.01). (4) After 3 days of culture, ANP was weakly expressed in HPCs from patients with permanent AF but not from patients with paroxysmal AF and SR. CONCLUSIONS: Peripheral blood HPCs together with plasma ANP and SDF-1alpha were significantly increased in patients with permanent AF. CD34+HPCs were positive correlated with the plasma levels of ANP and SDF-1alpha.