ABSTRACT
OBJECTIVE: To investigate the expressions of sphingosine 1-phosphate (S1P) and S1P G-protein-coupled receptor 1 (S1PR1) in pulmonary ischemia reperfusion injury (PIRI) tissues and explore their relationship. METHODS: The model of PIRI was established in vivo male C57BL/6 mice (n=8). The left pulmonary hilum was occluded for 30 min with a microvascular clamp through a left thoracotomy. Reperfusion began with removal of the clamp. Normal group (n=8) and sham group (n=8) were set as control. The hematoxylin and eosin (HE) staining of ultrastructural changes and wet-to-dry mass ratio in lung tissues were measured for judging the succeed model. The mRNA expressions of sphingosine kinase 1 (SphK1) and S1PR1 were determined by real-time PCR, and ELISA was used to detect the concentrations of S1P and S1PR1 in the lung tissues. RESULTS: The mRNA expressions of SphK1, S1PR1 and the concentrations of S1P and S1PR1 and wet-to-dry mass ratio of the lung tissues in ischemia-reperfusion mice were higher than those normal mice and sham operation mice (P<0.05). CONCLUSIONS: The increased expressions of S1P and S1PR1 in lung tissues after PIRI suggest that the S1P/S1PR1 signal pathway is involved in the pathophysiological process of PIRI, and may be a potential therapeutic target for it.
ABSTRACT
<p><b>BACKGROUND</b>Catheter-based renal denervation (RDN) is a novel treatment for resistant hypertension (RH). A recent meta-analysis reported that RDN did not significantly reduce blood pressure (BP) based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations.</p><p><b>METHODS</b>This was a meta-analysis of 9 randomized clinical trials (RCTs) among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure (SBP) level, antihypertensive medication change rates, and coronary heart disease (CHD).</p><p><b>RESULTS</b>In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-h SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP ≥155 mmHg (1 mmHg = 0.133 kPa) and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months (P = 0.100 and P= 0.009, respectively). Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months (P < 0.001).</p><p><b>CONCLUSIONS</b>In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBP.</p>
ABSTRACT
<p><b>OBJECTIVE</b>Fabry disease is a rare lysosome storage disease featuring X-linked recessive inheritance. The study was to explore potential mutations of alpha-galactosidase A (GLA) gene and their correlation with clinic manifestations in three Chinese pedigrees with Fabry disease.</p><p><b>METHODS</b>All exons and flanking sequences of GLA gene were amplified with PCR. Potential mutations were detected with bidirectional DNA sequencing. Correlation between particular mutations and clinic features were analyzed.</p><p><b>RESULTS</b>A unreported missense mutation, c.797A>C (D266A) in GLA exon 5 was identified in pedigree 1. Also in exon 5, a missense mutation c.644A>G (N215S) was found in pedigree 2. In pedigree 3, a nonsense mutation c.355C>T (Q119X) was found in exon 2. The c.797A>C mutation was not detected in 200 unrelated male controls. The probands of pedigrees 1 and 3 had presented mainly with skin damage and chronic renal insufficiency, whilst the proband of pedigree 2 had presented with hypertrophic cardiomyopathy.</p><p><b>CONCLUSION</b>The unreported c.797A>C (D266A) mutation is the sixth missense type mutation of the 266th codon of GLA gene, and all other 5 missense mutations reported previously had been confirmed to be responsible for Fabry disease. The c.797A>C mutation, not found in 200 unrelated male controls, may be the causative mutation in pedigree 1. The c.644A>G and c.355C>T mutations were first detected in Chinese patients. Variable phenotypes of Fabry disease may be in part attributed to the natures of particular mutations of GLA gene.</p>
