HLA-DR4 antigen and idiopathic dilated cardiomyopathy susceptibility: a meta-analysis involving 11,761 subjects

Idiopathic dilated cardiomyopathy (IDC) has been hypothesized as a multifactorial disorder initiated by an environment trigger in individuals with predisposing human leukocyte antigen (HLA) alleles. Published data on the association between HLA-DR4 antigen and IDC risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Studies in English-language articles were identified by a search of PubMed and Embase database (inception to June 2010). A total of 19 case-control studies including 1378 cases and 10,383 controls provided data on the association between HLA-DR4 antigen and genetic susceptibility to IDC. Overall, statistically elevated frequency of HLA-DR4 allele [OR (odds ratio), 1.58; 95% CI (confidence interval), 1.21-2.07; P = 0.0009] was found in patients with IDC compared with controls. When stratified by myocardial biopsy or non-biopsy cases, statistically increased risks were found for IDC in both subgroups. In the subgroup analysis by ethnicity, significantly increased risk was found among Europeans from 12 case-control studies (OR, 1.54; 95% CI, 1.11-2.12; P = 0.009). In conclusion, our results suggest that HLA-DR4 antigen is a low-penetrant risk factor for developing IDC in Europeans.     

Analysis of antigen epitopes and molecular pathogenic characteristics of the 2009 H1N1 pandemic influenza A virus in China

In order to further predict the epidemic trend and develop vaccines for 2009 H1N1 virus, we monitored its epitopes and molecular pathogenic characteristics during the epidemic process. We also analyzed the similarity of antigenic and genetic characteristics among the novel 2009 H1N1, representative seasonal H1N1 strains, and vaccine strains. 2009 H1N1 isolates had high similarity of hemagglutinin (HA) antigenic sites with H1N1 viruses isolated before 1940 and up to 80.0% similarity with 1918 H1N1. The elderly people born before 1940 have relatively low 2009 H1N1 infection rate, which might be responsible for their previous infection with either 1918 H1N1 virus or an early progeny. Compared to seasonal H1N1 vaccine strains from 1999 to 2010, the HA, neuraminidase (NA), and nucleoprotein (NP) proteins of the isolates had highly conserved CTL epitopes (60.5-65.8%, 69.6-82.6%, and 76.7%, respectively). The seriousness and mortality rate of 2009 H1N1 infections were similar to seasonal influenza, which may be related to the molecular characteristics of low toxicity of 2009 H1N1 and cross-T-cell immunity, due to vaccination or exposure to seasonal H1N1 virus. Some strains of 2009 H1N1 acquired mutations at antigenic and glycosylation sites. It is of particular interest that Haishu/SWL110/10 and Beijing/SE2649/09, isolated after November 2009, gained a new glycosylation site at the position 179 of HA protein, near the RBD. Thus, in the future, vaccination with glycosylated 2009 H1N1 virus may prevent the seasonal epidemic caused by strains with glycosylation site mutation near the receptor binding domain (RBD).     

Expression of Pirh2, a p27(Kip1) ubiquitin ligase, in hepatocellular carcinoma: correlation with p27(Kip1) and cell proliferation

p53-Induced ring-H2 protein (Pirh2), a recently identified ubiquitin-protein ligase, interacts with p27(Kip1) to promote ubiquitination of p27(Kip1) independently of p53. High Pirh2 and low p27(Kip1) immunoreactivity are associated with a poor prognosis in several cancers, including resistant phenotypes. In the present study, we investigated the role of Pirh2 and p27(Kip1) in human hepatocellular carcinoma (HCC) progression. Immunohistochemical analysis was performed on formalin-fixed paraffin sections of 87 specimens. Statistical analysis showed that expression of Pirh2 was negatively related to p27(Kip1) expression (r = 0.787; P < .05), and Pirh2 expression correlated significantly with histologic grade (P < .001), venous invasion (P = .004), tumor size (P = .024), and the presence of multiple tumor-bearing lymph nodes (P = .017), whereas p27(Kip1) expression correlated significantly with histologic grade (P < .001), venous invasion (P = .048), and cirrhosis (P = .028). By Kaplan-Meier analysis, the survival curves of low versus high expressers of Pirh2 and p27(Kip1) showed significant separation (P < .01). Molecular interaction could be demonstrated between Pirh2 and p27(Kip1) in three HCC cell lines. In vitro, following release of two HCC cell lines from serum starvation, the expression of Pirh2 was upregulated, whereas p27(Kip1) was downregulated. Our results suggest that Pirh2 mediates the degradation of p27(Kip1) and participates in cell proliferation in human HCC. These findings provide a rational framework for further development of Pirh2 inhibitors as a novel class of anti-tumor agents.     

Triptolide inhibits rat vascular smooth muscle cell proliferation and cell cycle progression via attenuation of ERK1/2 and Rb phosphorylation

Background

Drug-eluting stents have demonstrated a substantial reduction of restenosis and currently are gaining a leading position in the intervention field. Triptolide, a purified extract from Chinese herb medicine Tripterygium wilfordii hook F, exhibits antiproliferative and pro-apoptotic function in vitro and in vivo. In the present study, we investigated effects of triptolide on in-stent restenosis in vivo and in vitro, and study the biological mechanism of this drug.

Methods

Rat aortic smooth muscle cells were cultured and treated with different concentration of triptolide (0, 1, 10, and 50 nM). For cell viability, we used trypan blue exclusion (TBE) survival assay. Flow cytometry was used to study the influence of triptolide on VSMCs cell cycle. Signal proteins were detected by western blotting analysis. Triptolide coated stents had been implanted in the iliac arteries of New Zealand rabbits. After 4 weeks, the stented iliac artery segments were processed for embedding, staining and histomorphometric analysis.

Results

Triptolide of concentration 10 nM, 50 nM significantly inhibited fetal calf serum-induced VSMC proliferation (p < 0.05). The accumulation of triptolide-treated cells at the G1/S-interphase was dose dependent. Triptolide completely blocked the cell cycle progression at 50 nM. Western blotting analysis showed decreased ERK1/2 MAP kinase phosphorylation level, significantly increased p21^cip1 expression and reduced retinoblastoma protein (pRb) phosphorylation after 24 h of triptolide treatment. 4 weeks after the surgery, the arterial wall morphology was shown that triptolide-coated stent has less neointimal vs bare metal stent.

Conclusions

Our study indicates that triptolide exert inhibitory effect on VSMC proliferation, inactivation of MAPK pathway and modulation of cell cycle proteins p21^cip1 and Rb are relating mechanisms. Triptolide drug-eluting stents attenuated neointimal formation after stent implantation in rabbit vessel. We believe that triptolide may potentially be useful in treating cardiovascular restenosis after PCI.     

Transcranial magnetic stimulation in different current directions activates separate cortical circuits

Transcranial magnetic stimulation (TMS) to the primary motor cortex (M1) produces a series of corticospinal descending waves, with a direct (D) wave followed by several indirect (I) waves. TMS inducing posterior-anterior (PA) current in the brain predominantly recruits the early I1-wave, whereas anterior-posterior (AP) directed current preferentially recruits the late I3-wave. However, it is not known whether I-waves elicited by different current directions are mediated by the same neuronal populations. We studied the neuronal mechanisms mediating I-waves by examining the influence of short-latency afferent inhibition (SAI) on various I-waves. SAI was tested with electrical median nerve stimulation at the wrist followed by TMS to the contralateral M1 at different current directions. Surface electromyograms and single motor units were recorded from the first dorsal interosseous muscle. SAI was weaker for the AP compared with that for the PA current direction. With increasing median nerve stimulation intensities, SAI increased for the PA direction but showed a U-shaped relationship for the AP direction. SAI produced more inhibition of late I-waves generated by PA than those generated by AP current direction. We conclude that late I-waves generated by PA and AP current directions are mediated by different neuronal mechanisms.     

糖尿病重症脑梗死患者早期肠内营养的效果观察及护理

目的探讨早期肠内营养对2型糖尿病重症脑梗死患者身体功能恢复的效果。方法将84例患者随机分为观察组（42例）和对照组（42例）。对照组行肠外营养支持3～4d后予鼻饲流质,观察组行早期肠内营养,2周后评价效果。结果观察组营养状况、神经功能缺损程度评分显著优于对照组（均P〈0．05）。两组不良反应及并发症发生率（除外上消化道出血）比较,差异无统计学意义（均P〉0．05）。结论早期肠内营养能够保持2型糖尿病重症脑梗死患者正常营养状态并有利于神经功能的恢复,且安全。     

Successful use of posterior instrumented spinal fusion alone for scoliosis in 19 patients with neurofibromatosis type-1 followed up for at least 25 months

Introduction  Posterior instrumented fusion alone has been considered inadequate to correct scoliosis in most patients with neurofibromatosis type-1 (NF-1) because of their weak bone structure. This study was undertaken to evaluate whether the extension of fusion one level beyond the conventional fusion level would enable posterior instrumented fusion alone to be as effective as anterior–posterior fusion in treating patients with NF-1 and scoliosis who are more than 10 years old and whose scoliosis is <90°. Methods  Nineteen patients with NF-1 were treated surgically with long, posterior instrumented fusion for scoliosis from 1998 to 2004. Among the patients, 3 had nondystrophic curves, and 16 had dystrophic curves. Posterior fusions were performed that used abundant bone grafts, and included neutral and stable vertebrae in both the coronal and sagittal planes and any coronal curves of more than 40°. Results  The mean coronal and sagittal Cobb’s angles in the nondystrophic curves were 79° and 16° before surgery, 31° and 12° after surgery, and 37° and 15° at follow-up, respectively. In the dystrophic thoracic curves, the Cobb’s angles in the coronal and sagittal planes before and after surgery and at follow-up were 68° and 31°, 27° and 28°, and 33°and 30°, respectively. There were no cases of coronal or sagittal decompensation, neurologic complications, or infections. There were eight (42.1%) complications, three intraoperative and five late. Pseudarthrosis with instrumentation failure that required revision surgery occurred in one (5.2%) patient. Conclusions  These results demonstrate that a satisfactory stabilization of scoliosis can be achieved by posterior fusion with instrumentation alone in patients with NF-1 who are more than 10 years old, and whose scoliosis is <90°. Contributions of authors: All authors meet the criteria for authorship. All authors accept full responsibility for the study, had access to the data, analyzed the data, and made the decision to publish.