Hepatic Cyp1a2 Expression Reduction during Inflammation Elicited in a Rat Model of Intermittent Hypoxia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Intermittent hypoxia (IH) is a key element of obstructive sleep apnea (OSA) that can lead to disorders in the liver. In this study, IH was established in a rat model to examine its effects on the expression of hepatic cytochrome P450 (CYP) and CYP regulators, including nuclear receptors.</p><p><b>METHODS</b>Hematoxylin and eosin staining was conducted to analyze the general pathology of the liver of rats exposed to IH. The messenger RNA (mRNA) expression levels of inflammatory cytokines, CYPs, nuclear factor-κB (NF-κB), and nuclear factors in the liver were measured by quantitative reverse transcription polymerase chain reaction.</p><p><b>RESULTS</b>We found inflammatory infiltrates in the liver of rats exposed to IH. The mRNA expression level of interleukin-1beta was increased in the liver of the IH-exposed rats (0.005 ± 0.001 vs. 0.038 ± 0.008, P = 0.042), whereas the mRNA expression level of Cyp1a2 was downregulated (0.022 ± 0.002 vs. 0.0050 ± 0.0002, P = 0.029). The hepatic level of transcription factor NF-κB was also reduced in the IH group relative to that in the control group, but the difference was not statistically significant and was parallel to the expression of the pregnane X receptor and constitutive androstane receptor. However, the decreased expression of the glucocorticoid receptor upon IH treatment was statistically significant (0.056 ± 0.012 vs. 0.032 ± 0.005, P = 0.035).</p><p><b>CONCLUSIONS</b>These results indicate a decrease in expression of hepatic CYPs and their regulator GR in rats exposed to IH. Therefore, this should be noted for patients on medication, especially those on drugs metabolized via the hepatic system, and close attention should be paid to the liver function of patients with OSA-associated IH.</p>

Impaired Capacity of Fibroblasts to Support Airway Epithelial Progenitors in Bronchiolitis Obliterans Syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bronchiolitis obliterans syndrome (BOS) often develops in transplant patients and results in injury to the respiratory and terminal airway epithelium. Owing to its rising incidence, the pathogenesis of BOS is currently an area of intensive research. Studies have shown that injury to the respiratory epithelium results in dysregulation of epithelial repair. Airway epithelial regeneration is supported by stromal cells, including fibroblasts. This study aimed to investigate whether the supportive role of lung fibroblasts is altered in BOS.</p><p><b>METHODS</b>Suspensions of lung cells were prepared by enzyme digestion. Lung progenitor cells (LPCs) were separated by fluorescence-activated cell sorting. Lung fibroblasts from patients with BOS or healthy controls were mixed with sorted mouse LPCs to compare the colony-forming efficiency of LPCs by counting the number of colonies with a diameter of ≥50 μm in each culture. Statistical analyses were performed using the SPSS 17.0 software (SPSS Inc., USA). The paired Student's t-test was used to test for statistical significance.</p><p><b>RESULTS</b>LPCs were isolated with the surface phenotype of CD31-CD34-CD45- EpCAM+Sca-1+. The colony-forming efficiency of LPCs was significantly reduced when co-cultured with fibroblasts isolated from patients with BOS. The addition of SB431542 increased the colony-forming efficiency of LPCs to 1.8%; however, it was still significantly less than that in co-culture with healthy control fibroblasts (P < 0.05).</p><p><b>CONCLUSION</b>The epithelial-supportive capacity of fibroblasts is impaired in the development of BOS and suggest that inefficient repair of airway epithelium could contribute to persistent airway inflammation in BOS.</p>

Effect of low-molecular-weight heparin and urokinase on pulmonary arteries involved in pulmonary embolism / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pulmonary embolism (PE) is a common and often fatal disease. Early after pulmonary thromboembolism, inflammation and associated intimal hyperplasia occur within the pulmonary arteries, similar to what is observed with chronic thromboembolic pulmonary hypertension. This study tested the hypothesis that thrombolytic and anticoagulant agents would have anti-inflammatory effects or inhibit intimal hyperplasia of involved pulmonary arteries.</p><p><b>METHODS</b>Seventy-two male New Zealand white rabbits were randomly divided into two groups (54 rabbits in the PE group and 18 in the sham group). Experimental PE was induced in 54 rabbits by femoral vein injection of autologous blood clots and confirmed with pulmonary angiography, and other 18 rabbits underwent sham operations. Fifty-four rabbits in the PE group were randomly divided into three groups: a control group (treated with normal saline), a low-molecular- weight heparin (LMWH) group (treated with LMWH), and a urokinase (UK) group (treated with UK). Arterial blood gas was analyzed at 2, 7, and 28 days (n = 6 per time point by random group division), then lung tissues were removed and were analyzed for pro-inflammatory cytokines and chemokines, and were stained for intimal hyperplasia.</p><p><b>RESULTS</b>The overall survival of rabbits undergoing PE was 100%. PE distribution detected on digital signal angiography (DSA) and histopathology was shown in 67% of rabbits (36/54) in the bilateral low lobar pulmonary arteries (PAs). The results showed that alveolar-arterial partial pressure of oxygen (PO2) difference (PA-aO2) significantly increased and PO2 decreased in the control group compared with the sham group. Compared with controls, the UK group had a decreased level of PA-aO2 on day 2 (P < 0.05), however, there was no significant difference in the LMWH group. Compared with controls, the LMWH group had a decreased level of monocyte chemoattractant protein-1 (MCP-1) in affected tissue and serum samples on days 7 and 28 (P < 0.05), and the UK group had decreased levels on days 2 and 7 (P < 0.05). Compared with sham group, all PE groups had an increased level of interleukin-13 (IL-13) and transforming growth factor-β (TGF-β) in unaffected lung tissue samples at days 2 and 7. IL-13 in affected lung tissue in the LMWH group was decreased at all time points compared with controls (P < 0.05). However, TGF-β in affected lung tissue of the LMWH and UK groups increased at day 28. There was less intimal hyperplasia in involved pulmonary arteries at days 7 and 28 in the LMWH group compared with controls; there was no statistical difference in the UK group compared with controls.</p><p><b>CONCLUSIONS</b>UK treatment can rapidly improve the V/Q mismatch in PE and appears a short-term anti-inflammatory benefit. However, LMWH maybe inhibit the later local inflammatory reaction and reduce intimal hyperplasia.</p>

Protective effect of autophagy inhibition on ischemia-reperfusion-induced injury of N2a cells / 华中科技大学学报（医学）（英德文版）

Autophagy is a conserved and programmed catabolic process that degrades damaged proteins and organelles. But the underlying mechanism and functions of autophagy in the ischemia-reperfusion (IR)-induced injury are unknown. In this study, we employed simulated IR of N2a cells as an in vitro model of IR injury to the neurons and monitored autophagic processes. It was found that the levels of Beclin-1 (a key molecule of autophay complex, Beclin-1/class III PI3K) and LC-3II (an autophagy marker) were remarkably increased with time during the process of ischemia and the process of reperfusion after 90 min of ischemia, while the protein kinases p70S6K and mTOR which are involved in autophagy regulation showed delayed inactivation after reperfusion. Administration of 3-methyladenine (3MA), an inhibitor of class III PI3K, abolished autophagy during reperfusion, while employment of rapamycin, an inhibitor of mTORC1 (normally inducing autophagy), surprisingly weakened the induction of autophagy during reperfusion. Analyses of mitochondria function by relative cell viability demonstrated that autophagy inhibition by 3-MA attenuated the decline of mitochondria function during reperfusion. Our data demonstrated that there were two distinct dynamic patterns of autophagy during IR-induced N2a injury, Beclin-1/class III PI3K complex-dependent and mTORC1-dependent. Inhibition of over-autophagy improved cell survival. These suggest that targeting autophagy therapy will be a novel strategy to control IR-induced neuronal damage.

Protective effect of autophagy inhibition on ischemia-reperfusioninduced injury of N2a cells / 华中科技大学学报（医学）（英德文版）

Autophagy is a conserved and programmed catabolic process that degrades damaged proteins and organelles. But the underlying mechanism and functions of autophagy in the ischemiareperfusion (IR)-induced injury are unknown. In this study, we employed simulated IR of N2a cells as an in vitro model of IR injury to the neurons and monitored autophagic processes. It was found that the levels of Beclin-1 (a key molecule of autophay complex, Beclin-1/class III PI3K) and LC-3II (an autophagy marker) were remarkably increased with time during the process of ischemia and the process of reperfusion after 90 min of ischemia, while the protein kinases p70S6K and mTOR which are involved in autophagy regulation showed delayed inactivation after reperfusion. Administration of 3-methyladenine (3MA), an inhibitor of class III PI3K, abolished autophagy during reperfusion, while employment of rapamycin, an inhibitor of mTORC1 (normally inducing autophagy), surprisingly weakened the induction of autophagy during reperfusion. Analyses of mitochondria function by relative cell viability demonstrated that autophagy inhibition by 3-MA attenuated the decline of mitochondria function during reperfusion. Our data demonstrated that there were two distinct dynamic patterns of autophagy during IR-induced N2a injury, Beclin-1/class III PI3K complex-dependent and mTORC1-dependent. Inhibition of over-autophagy improved cell survival. These suggest that targeting autophagy therapy will be a novel strategy to control IR-induced neuronal damage.

Idiopathic pulmonary vein thrombosis extending to left atrium: a case report with a literature review / 中华医学杂志(英文版)

Pulmonary vein thrombosis is a rare disease and is usually represented as a complication of atrial fibrillation, pulmonary tumors, and lobectomy. Although it is a potentially life threatening condition, the venous disease is easy to misdiagnose because of the non-specific symptoms. In this article, we present a 30-year-old patient who suffered from pulmonary vein thrombosis without any causes. He was diagnosed with other pulmonary disorders till the thrombus within the pulmonary vein extended into the left atrium. Left atrium mass resection and a left lower lobectomy were undertaken with relative urgency. The postoperative course was uneventful. The patient received a long course of oral anticoagulant therapy.