Hydroxycitric Acid Tripotassium Hydrate Attenuates Monocrotaline and Hypoxia-Induced Pulmonary Hypertension in Rats.

This study investigated the effects of hydroxycitric acid tripotassium hydrate on right ventricular function, myocardial and pulmonary vascular remodeling in rats with pulmonary hypertension, and possible mechanisms. METHODS: Pulmonary hypertension was induced in male Sprague-Dawley rats by a single subcutaneous injection of monocrotaline or hypoxic chamber. In vivo, inflammatory cytokine (including TNF-α, IL-1ß, IL-6, and TGF-ß, the level of SOD) expression, superoxide dismutase and hydrogen peroxide levels, and p-IκBα and p65 expressions were detected. In vitro, pulmonary artery smooth muscle cell proliferation and migration, ROS production, and hypoxia-inducible factor-1 expression were also studied. RESULTS: Hydroxycitric acid tripotassium hydrate decreased right ventricular systolic pressure and reduced right ventricular fibrosis and pulmonary vascular remodeling in rats with two kinds of pulmonary hypertension. Moreover, the expression of both inflammatory and oxidative stress factors was effectively reduced, and the p65 signaling pathway was found to be inhibited in this study. Additionally, hydroxycitric acid tripotassium hydrate inhibited human pulmonary artery smooth cell proliferation and migration in vitro. CONCLUSIONS: This study shows that hydroxycitric acid tripotassium hydrate can alleviate pulmonary hypertension caused by hypoxia and monocycloline in rats, improve remodeling of the right ventricle and pulmonary artery, and inhibit pulmonary artery smooth muscle cell proliferation and migration. The protective effects may be achieved by regulating inflammation and oxidative stress through the p65 signaling pathway.

RNA-binding protein CELF6 modulates transcription and splicing levels of genes associated with tumorigenesis in lung cancer A549 cells.

CELF6 (CUGBP Elav-Like Family Member 6), a canonical RNA binding protein (RBP), plays important roles in post-transcriptional regulation of pre-mRNAs. However, the underlying mechanism of lower expressed CELF6 in lung cancer tissues is still unclear. In this study, we increased CELF6 manually in lung cancer cell line (A549) and utilized transcriptome sequencing (RNA-seq) technology to screen out differentially expressed genes (DEGs) and alternative splicing events (ASEs) after CELF6 over-expression (CELF6-OE). We found that CELF6-OE induced 417 up-regulated and 1,351 down-regulated DEGs. Functional analysis of down-regulated DEGs showed that they were highly enriched in immune/inflammation response- related pathways and cell adhesion molecules (CAMs). We also found that CELF6 inhibited the expression of many immune-related genes, including TNFSF10, CCL5, JUNB, BIRC3, MLKL, PIK3R2, CCL20, STAT1, MYD88, and CFS1, which mainly promote tumorigenesis in lung cancer. The dysregulated DEGs were also validated by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) experiment. In addition, CELF6 regulates the splicing pattern of large number of genes that are enriched in p53 signaling pathway and apoptosis, including TP53 and CD44. In summary, we made an extensive analysis of the transcriptome profile of gene expression and alternative splicing by CELF6-OE, providing a global understanding of the target genes and underlying regulation mechanisms mediated by CELF6 in the pathogenesis and development of lung cancer.

Alternatively Expressed Transcripts Analysis of Non-Small Cell Lung Cancer Cells under Different Hypoxic Microenvironment.

Globally, non-small cell lung cancer (NSCLC) is the most fatal form of malignancy. Numerous studies have shown that people living at high altitudes are at a higher risk for cancer. Hypoxia is one of the most important features in high altitude area. Compared with normal cells, cancer cells are more adapted to hypoxia atmosphere. However, at high altitudes, hypoxic conditions are also accompanied by other altered environmental conditions. To identify the single influence of hypoxia, we performed second-generation sequencing to identify gene expression changes triggered by the different oxygen concentrations. We identified 782 genes in A549 cells and 1122 genes in H520 cells that showed altered expression by the combined analysis in 5% oxygen concentration group and 1% oxygen concentration group control group. We further analyzed these targets and found 113 genes altered in both cell lines. Interestingly, we found KxD1 was the only one in both top 10 lists. Further analysis revealed KxD1 to be significantly elevated in NSCLC patients and negatively correlated with prognosis in stage I and II NSCLC patients. Moreover, this correlation reversed in stage III patients. Additionally, compared with patients who only received clean margin operation or chemotherapy, patients who received radiotherapy also showed opposite result. Thus, KxD1 may be a promising target for the treatment of NSCLC in high-altitude areas.

Uric acid lowering effect of Tibetan Medicine RuPeng15 powder in animal models of hyperuricemia.

OBJECTIVE: To evaluate the influence of the Tibetan medicine RuPeng15 powder (RPP15) on uric acid levels, and explore its possible mechanisms of action in hyperuricemic animal models. METHODS: Hyperuricemic mice were generated by orally administering yeast extract paste twice daily (30 g/kg) for 8 days, to mimic human hyperuricemia induced by high-protein diets. Hyperuricemic rats were generated by intraperitoneal injection of 250 mg/kg potassium oxonate to each animal 1 h before the last oral administration of test compounds, which raised the serum uric acid level by inhibiting the decomposition of uric acid. Levels of uric acid and creatinine in serum and urine were detected by the phosphotungstic acid and picric acid methods respectively, and the activity of xanthine oxidase (XOD) was assayed using a commercial test kit. RESULTS: RPP15 (0.4, 0.8, 1.2 g/kg) significantly decreased the level of serum uric acid in healthy rats (P < 0.05). Furthermore, hyperuricemic rats treated with RPP15 (0.4, 0.8, 1.2 g/kg) had lower serum uric acid levels (P < 0.05), accompanied by lower urine uric acid (P < 0.05). For the hyperuricemic mice, the levels of uric acid in the serum decreased significantly (P < 0.05) and the activity of XOD in the liver was restored to normal levels after treatment with RPP15 (P < 0.05). CONCLUSION: RPP15 (0.4, 0.8, 1.2 g/kg) demonstrated an anti-hyperuricemic effect on both healthy and hyperuricemic animals, and the mechanism is most likely associated with inhibiting the activity of XOD.

Clinical analysis of thoracoscopic surgery combined with intraoperative autologous blood transfusion in the treatment of traumatic hemothorax.

From January 2013 to January 2015, 19 patients of traumatic hemothorax with hemorrhagic shock were treated in our department by thoracoscopic surgery combined with autologous blood transfusion. This study retrospectively analyzed the therapeutic effect and shared our experience. The average amount of blood transfused back was 662.41 ml ± 269.15 ml. None of the patients developed transfusion reaction and were all discharged uneventfully. Thoracoscopic surgery combined with autologous blood trans- fusion is effective in the rescue of patients with progressive hemothorax and hemorrhagic shock. When corresponding indications are well managed, treatment for these patients is quicker, safer, and more effective.

Multiple metallic foreign bodies accidentally detected in different body cavities: a case report.

We accidentally found an unusual case of a middle aged Tibetan woman who had eight metallic foreign bodies (eight needles) in her head, chest and abdomen. These needles were not related to any surgical intervention or trauma. The diagnosis "metallic foreign bodies" cannot usually be made in an acute setting. Some patients may present chronic symptoms, such as infection or pain. However, in some cases, the patients do not have any symptoms.

[Effect of prone position on the oxygenation of patients with acute respiratory distress syndrome after failure recruitment maneuvers at high altitudes].

OBJECTIVE: To assess the effect of prone position on the oxygenation of patients with acute respiratory distress syndrome (ARDS) after recruitment maneuvers (RM) failure at high altitudes. METHODS: Forty-one ARDS patients who were invalid for RM therapy at the altitude of 2260 metres area hospital were enrolled[mean oxygenation index (PaO(2)/FiO(2)) increased than RM<20% considered as RM invalid]. All were divided into acute respiratory distress syndrome (ARDSp) and extra-acute respiratory distress syndrome (ARDSexp) based on different etiology, and each group was randomly divided into the supine and the prone position group, i.e. that ARDSp prone position group (n=11), ARDSp supine group (n=9), ARDSexp prone position group (n=10), and ARDSexp supine group (n=11). Before ventilation and 1, 2, 3, 4 hours after ventilation, arterial partial pressure of oxygen (PaO(2)), PaO(2)/FiO(2), static lung compliance (Cst), airway resistance (Raw) were monitored. RESULTS: One hour after ventilation in ARDSexp prone position group, PaO(2)/FiO(2) was significantly higher than before ventilation (157.4±40.6 mm Hg vs. 129.3±48.7 mm Hg, P<0.05), and increased by ventilation time, peaked at 4 hours (219.1±41.1 mm Hg). Within 3 hours ventilation in ARDSexp prone position group, PaO(2)/FiO(2) was significantly higher compared with the other three groups, and there were no significant differences among the other three groups. PaO(2)/FiO(2) in ARDSp prone position group and ARDSexp prone position group at 4 hours of ventilation were significantly higher compared with the corresponding supine group (208.8±39.7 mm Hg vs. 127.4±47.1 mm Hg, 219.1±41.1 mm Hg vs. 124.9±50.8 mm Hg, both P<0.05). There was no statistically significant difference in Cst before and after ventilation, and there was no significant changes among the groups. Raw in ARDSp prone position group at 4 hours of ventilation were significantly reduced than before ventilation (6.8±1.7 cm H(2)O×L(-1)×s(-1) vs. 10.7±1.8 cm H(2)O×L(-1)×s(-1), P<0.05), and significantly lower than the other three groups. There was no statistically significant difference in RAW among other three groups at each time point. CONCLUSION: Prone position can improve RM oxygenation invalid ARDS patients at high altitudes.