Adjunctive Manual Thrombus Aspiration during ST-Segment Elevation Myocardial Infarction: A Meta-Analysis of Randomized Controlled Trials

Objective

The aim of this study was to synthesize evidence by examining the effects of manual thrombus aspiration on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI).

Methods and Results

A total of 26 randomized controlled trials (RCTs), enrolling 11,780 patients, with 5,869 patients randomized to manual thrombus aspiration and 5,911 patients randomized to conventional percutaneous coronary intervention (PCI), were included in the meta-analysis. Separate clinical outcome analyses were based on different follow-up periods. There were no statistically reductions in the incidences of mortality (risk ratio [RR], 0.86 [95% confidence interval [CI]: 0.73 to 1.02]), reinfarction (RR, 0.62 [CI, 0.31 to 1.32]) or target vessel revascularization (RR, 0.89 [CI, 0.75 to 1.05]) in the manual thrombus aspiration arm at 12 to 24 months of follow-up. The composite major adverse cardiac events (MACEs) outcomes were significantly lower in the manual thrombus aspiration arm over the long-term follow-up (RR, 0.76 [CI, 0.63 to 0.91]). A lower incidence of reinfarction was observed in the hospital to 30 days (RR, 0.59 [CI, 0.37 to 0.92]).

Conclusion

The present meta-analysis suggested that there was no evidence that using manual thrombus aspiration in patients with STEMI could provide distinct benefits in long-term clinical outcomes.     

Naloxone for Severe Traumatic Brain Injury: A Meta-Analysis

Objective

The efficiency of naloxone for the management of secondary brain injury after severe traumatic brain injury (sTBI) remains undefined. The aim of this study is to evaluate the current evidence regarding the clinical efficiency and safety of naloxone as a treatment for sTBI in mainland China.

Methodology/Principal Findings

A systematic search of the China Biology Medicine disc (CBM), China Science and Technology Journal Database (VIP), China National Knowledge Internet (CNKI), and Wan Fang Database was performed to identify randomized controlled trials (RCTs) of naloxone treatment for patients with sTBI in mainland China. The quality of the included trials was assessed, and the RevMan 5.1 software was employed to conduct this meta-analysis. Nineteen RCTs including 2332 patients were included in this study. The odds ratio (OR) showed statistically significant differences between the naloxone group and the control group (placebo) in terms of mortality at 18 months after treatment (OR, 0.51, 95%CI: 0.38–0.67; p<0.00001), prevalence of abnormal heart rates (OR, 0.30, 95%CI: 0.21–0.43; p<0.00001), abnormal breathing rate (OR, 0.25, 95%CI: 0.17–0.36; p<0.00001) at discharge, the level of intracranial pressure at discharge (OR, 2.00, 95%CI: 1.41–2.83; p = 0.0001), verbal or physical dysfunction rate (OR, 0.65, 95%CI: 0.43–0.98; p = 0.04), and severe disability rate (OR, 0.47, 95%CI: 0.30–0.73; p = 0.0001) at 18 months after the treatment. The mean difference (MD) showed statistically significant differences in awakening time at discharge (MD, −4.81, 95%CI: −5.49 to −4.12; p<0.00001), and GCS at 3 days (MD, 1.00, 95%CI: 0.70–1.30; p<0.00001) and 10 days (MD, 1.76, 95%CI: 1.55–1.97; p<0.00001) after treatment comparing naloxone with placebo group.

Conclusions/Significance

This study indicated that applying naloxone in the early stage for sTBI patients might effectively reduce mortality, control intracranial pressure (ICP), and significantly improve the prognosis.     

Crystal Structure Confirmation of JHP933 as a Nucleotidyltransferase Superfamily Protein from Helicobacter pylori Strain J99

Helicobacter pylori is a well-known pathogen involved in the development of peptic ulcer, gastric adenocarcinoma and other forms of gastric cancer. Recently, there has been more considerable interest in strain-specific genes located in plasticity regions with great genetic variability. However, little is known about many of these genes. Studies suggested that certain genes in this region may play key roles in the pathogenesis of H. pylori-associated gastroduodenal diseases. JHP933, a conserved putative protein of unknown function, is encoded by the gene in plasticity region of H. pylori strain J99. Here we have determined the structure of JHP933. Our work demonstrates that JHP933 is a nucleotidyltransferase superfamily protein with a characteristic αβαβαβα topology. A superposition demonstrates overall structural homology of the JHP933 N-terminal fragment with lincosamide antibiotic adenylyltransferase LinA and identifies a possible substrate-binding cleft of JHP933. Furthermore, through structural comparison with LinA and LinB, we pinpoint conservative active site residues which may contribute to divalent ion coordination and substrate binding.     

Activation of farnesoid X receptor (FXR) protects against fructose-induced liver steatosis via inflammatory inhibition and ADRP reduction

Fructose is a key dietary factor in the development of nonalcoholic fatty liver disease (NAFLD). Here we investigated whether WAY-362450 (WAY), a potent synthetic and orally active FXR agonist, protects against fructose-induced steatosis and the underlying mechanisms. C57BL/6J mice, fed 30% fructose for 8 weeks, were treated with or without WAY, 30 mg/kg, for 20 days. The elevation of serum and hepatic triglyceride in mice fed 30% fructose was reversed by WAY treatment. Histologically, WAY significantly reduced triglyceride accumulation in liver, attenuated microphage infiltration and protected the junction integrity in intestine. Moreover, WAY remarkably decreased portal endotoxin level, and lowered serum TNFα concentration. In lipopolysaccharide (LPS)-induced NAFLD model, WAY attenuated serum TNFα level. Moreover, WAY suppressed LPS-induced expression of hepatic lipid droplet protein adipose differentiation-related protein (ADRP), down-regulation of it in mice fed 30% fructose. Furthermore, WAY repressed lipid accumulation and ADRP expression in a dose-dependent manner in palmitic acid (PA)-treated HepG2 and Huh7 cells. WAY suppressed TNFα-induced ADRP up-regulation via competing with AP-1 for ADRP promoter binding region. Together, our findings suggest that WAY, an FXR agonist, attenuates liver steatosis through multiple mechanisms critically involved in the development of hepatosteatosis, and represents a candidate for NAFLD treatment.     

Histone H3K56 Acetylation Is Required for Quelling-induced Small RNA Production through Its Role in Homologous Recombination

Quelling and DNA damage-induced small RNA (qiRNA) production are RNA interference (RNAi)-related phenomenon from repetitive genomic loci in Neurospora. We have recently proposed that homologous recombination from repetitive DNA loci allows the RNAi pathway to recognize repetitive DNA to produce small RNA. However, the mechanistic detail of this pathway remains largely unclear. By systematically screening the Neurospora knock-out library, we identified RTT109 as a novel component required for small RNA production. RTT109 is a histone acetyltransferase for histone H3 lysine 56 (H3K56) and H3K56 acetylation is essential for the small RNA biogenesis pathway. Furthermore, we showed that RTT109 is required for homologous recombination and H3K56Ac is enriched around double strand break, which overlaps with RAD51 binding. Taken together, our results suggest that H3K56 acetylation is required for small RNA production through its role in homologous recombination.     

幽门螺杆菌jhp947基因对C57BL/6小鼠致病性研究

摘要：【目的】 检测jhp947对幽门螺杆菌(Helicobacter pylori,Hp )所致动物胃上皮细胞病变和基因表达的影响。【方法】 将27只无特定病原体的（specified-pathogens free,SPF）6 w 龄 C57BL/6小鼠随机分成3组,分别以J99 、△J99-947（缺失jhp947基因）和PBS灌胃,菌量为109CFU/mL,0、2、4 d各一次,4w后宰杀所有小鼠,无菌操作取胃组织,分别作快速尿素酶试验,Hp培养,组织病理学检查;免疫组化检测ESE-3A、NDRG1、MATP基因表达;半定量RT-PCR检测jhp947基因对小鼠ESE-3A、NADG1、MATP等基因转录的影响。【结果】 J99组和△J99-947组快速尿素酶试验和Hp培养的阳性率均为100%,PBS对照组快速尿素酶试验和Hp培养阴性。 组织病理学检查,PBS对照组小鼠胃黏膜100%正常, J99组小鼠胃黏膜33.3%（3/9）轻度糜烂,66.7%（6/9）重度糜烂。△J99-947组小鼠胃黏膜22.2%（2/9）正常,77.8%（7/9）轻度糜烂,没有重度糜烂。J99组小鼠胃黏膜的损伤比△J99-947组重。 免疫组化检测结果, J99组比△J99-947组ESE-3A、NDRG1、MATP表达显著降低（p<0.05）。 半定量RT-PCR检测结果, J99组比△J99-947组ESE-3A、NDRG1、MATP表达显著降低（p<0.05）。【结论】 JHP947基因存在可使Hp感染所致的胃黏膜损伤程度加重。在体内jhp947基因可能通过下调NDRG1、MATP等肿瘤抑制基因的表达,这可能与胃癌的发生有关。     

Quantitative classification and ordination of forest communities in Pangquangou National Nature Reserve

Quantitative analysis of ecological relationships between vegetation and the environment has become an essential means in the field of research of modern vegetation ecology. In this article, based on data from 84 quadrates, forest communities in this reserve were investigated using TWINSPAN, DCA and DCCA. The results will be helpful in the construction and development of Pangquangou National Nature Reserve. Using TWINSPAN, the forest communities were classified into seven types. The distribution pattern of vegetation reflects the comprehensive influence of environments. The results of DCA and DCCA clearly reflect the relationship between the pattern of forest communities and environmental gradients. The ordination result of DCCA indicates that altitude is more important than other environmental factors because the change of altitude gradient will lead to changes in the temperature and humidity gradients. The first of the DCA ordination axes indicates the humidity gradient, and the second indicates the temperature gradient. All these results show that the main factors restricting the distribution of communities in this reserve are temperature and humidity. The ecological meaning of the ordination axis in DCCA is much clearer than that in DCA, and the species-environment correlation of DCCA is more obvious than DCA. The first DCCA axis indicates the altitude gradient among the communities, while the second is the gradient in aspect and slope among the communities. DCCA ordination can simultaneously express similarities of species and environment. Therefore, the quadrat location in the DCCA ordination figure is much closer than in the DCA.     

Reduction of CYP450 inhibition in the 4-[(1H-imidazol-4-yl)methyl]piperidine series of histamine H3 receptor antagonists

A novel series of histamine H3 receptor antagonists based on the 4-[(1H-imidazol-4-yl)methyl]piperidine template displaying low CYP2D6 and CYP3A4 inhibitory profiles has been identified. Structural features responsible for the reduction of P450 activity, a typical liability of 4-substituted imidazoles, have been established.