Results of Vertebral Augmentation Treatment for Patients of Painful Osteoporotic Vertebral Compression Fractures: A Meta-Analysis of Eight Randomized Controlled Trials

Background

In 2009 two RCTs were publicated to question the efficacy of vertebroplasty comparing with sham treatment (ST) in the New England Journal of Medicine (NEJM), which provoked an academic debate on the efficacy of PVA. The purposes of our study were to compare clinical differences in pain relief, spinal functional outcomes, and overall quality of life between PVA and CT for painful osteoporotic VCFs.

Methods

We searched PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and Web of Knowledge from January 1980 to June 2013 with Medical Subject Headings terms and keywords. Risk of bias in the included studies was assessed in accordance with the Cochrane risk of bias tool. In this Meta-analysis dichotomous and continuous variables were calculated using the risk ratio (RR) and standardized mean difference (SMD), respectively.

Results

Eight studies involving 987 patients met the criteria for inclusion. The VAS SMD was favoring the experimental group significantly (p < 0.001). Subgroup analysis suggested that the patients performed PVA with mean fracture age less than 3 months would got pain relief earlier and more durable than the control group (P <0.05). The SMD of spinal function assessed with RDQ and Oswestry LBP data was in favor of the experimental groups. QOL outcome improvement was demonstrated statistically significant at early, middle and late-term follow-up for PVA than the control group (P <0.05).

Conclusions

In conclusion, this meta-analysis, which evaluated PVA for osteoporotic VCFs, demonstrated significant improvement regarding VAS, spinal function and QOL outcomes. The optimal fracture age was less than 12 weeks.     

A 1.6-Mb Microdeletion in Chromosome 17q22 Leads to NOG-Related Symphalangism Spectrum Disorder without Intellectual Disability

Microdeletions in chromosome 17q22, where the NOG gene resides, have been reported leading to the NOG-related symphalangism spectrum disorder (NOG-SSD), intellectual disability and other developmental abnormalities. In this study we reported a dominant Chinese Han family segregating with typical NOG-SSD symptoms including proximal symphalangism, conductive hearing loss, amblyopia and strabismus, but not intellectual disability. Sanger sequencing identified no pathogenic mutation in the coding regions of candidate genes NOG, GDF5 and FGF9. SNP genotyping in the genomic region surrounding NOG identified loss of heterozygosity in the affected family members. By array comparative genomic hybridization and quantitative real-time polymerase chain reaction, we identified and mapped the breakpoints of a novel 1.6-Mb microdeletion in chromosome 17q22 that included NOG and twelve other genes. It is the first microdeletion reported in chromosome 17q22 that is associated with NOG-SSD only but not with intellectual disability. Our results may help identifying the dosage sensitive genes for intellectual disability and other developmental abnormalities in chromosome 17q22. Our study also suggested that genomic deletions in chromosome 17q22 should be screened in the NOG-SSD patients in which no pathogenic mutation is identified by conventional sequencing methods.     

Tryptase promotes human monocyte-derived macrophage foam cell formation by suppressing LXRα activation

Accumulated mast cells in atherosclerotic plaques secrete a high level of tryptase that may participate in the pathogenesis of atherosclerotic disease by diverse pathways. However, the role of tryptase in the lipid metabolism of macrophages remains to be defined. In the present study, we found that the addition of tryptase into THP-1-derived macrophages increased both intracellular lipid accumulation and total cholesterol level. Tryptase promoting foam cell formation was also observed by transmission electron microscope. These effects were resisted by APC366, a selective inhibitor of mast cell tryptase. Tryptase dramatically resisted 22RHC induced activation of LXRα protein expression, which can be reversed by SAM-11 (a PAR-2-specific neutralizing antibody) and reduced LXRα, ABCG1, ABCA1 and SREBP-1c mRNA levels and ABCG1 protein level, which were all blocked by APC366. PAR-2 agonist also redeemed 22RHC stimulation to activate LXRα, ABCG1 protein expression, and mRNA levels of LXRα and its target genes in both THP-1-derived macrophages and primary human monocyte-derived macrophages. In primary macrophages that were first transfected with PAR-2 siRNA and then treated with tryptase, both the ABCG1 protein level and mRNA levels of LXRα and ABCG1 were higher than those in the control siRNA-treated cells. Taken together, our data clarified the PAR-2 expression of human macrophages and suggested that tryptase might promote lipid accumulation in macrophages and foam cell formation by suppressing LXRα activation via PAR-2/LXRα/LXRα target genes signaling pathway. This investigation sheds a new light on the role of tryptase in foam cell formation and pathogenesis of atherosclerosis.     

HER2胞外段的克隆与原核表达

应用RT-PCR技术从人乳腺癌细胞系SK-BR-3中克隆出人表皮生长因子受体2(human epidermal growth factorreceptor 2,HER2)基因的胞外段,并插入到表达载体pET-30a中,得到重组表达载体pET30-HER2(Ex)。将该载体转化至大肠杆菌BL21(DE3)细胞中,加入IPTG进行诱导表达,成功获得HER2胞外段蛋白。分别提取培养液上清、大肠杆菌周质腔、细胞质可溶性及不可溶性组分蛋白进行SDS-PAGE电泳分析,确定目的蛋白定位于大肠杆菌细胞质包涵体中。通过改变诱导温度、诱导物浓度、诱导起始菌体密度和诱导时间,寻找最佳表达条件,使目的蛋白的表达量达到最高。结果表明,在37℃下,OD600达到1.0时,经终浓度为0.1 mmol/L的IPTG诱导4 h,目的蛋白的表达量最高。将重组表达菌进行超声破碎,分离出包涵体组分,经Ni2+亲和层析纯化后获得了纯度>90%的HER2胞外段蛋白,从而为抗HER2抗体的制备及肿瘤疫苗的研究奠定了基础。     

Clinical Value of ELISA-MPT64 for the Diagnosis of Tuberculous Pleurisy

Tuberculous pleurisy is one of the common extrapulmonary tuberculosis diseases. However, the diagnosis of tuberculous pleurisy still lacks a useful and effective tool, mainly due to paucity of Mycobacterium tuberculosis organisms in pleural effusion. Previous studies have confirmed that the MPT64 protein is highly specific and is secreted only by M. tuberculosis (MTB) complex. Therefore, in this study, we developed ELISA based on recombinantly expressed MPT64 in combination with rabbit polyclonal antibodies. The ELISA-MPT64 method was validated using MTB strains and tested against clinical samples. Nested PCR, Löwenstein–Jensen (L–J) culture and smear microscopy were employed as the comparative tools for assessing the performance of the assay. Our results demonstrate that the newly established ELISA-MPT64 technique is a rapid and useful tool for the diagnosis of tuberculous pleurisy.     

Hemorrhagic shock activation of NLRP3 inflammasome in lung endothelial cells

Hemorrhagic shock (HS) due to major trauma and surgery predisposes the host to the development of systemic inflammatory response syndrome (SIRS), including acute lung injury (ALI), through activating and exaggerating the innate immune response. IL-1β is a crucial proinflammatory cytokine that contributes to the development of SIRS and ALI. Lung endothelial cells (EC) are one important source of IL-1β, and the production of active IL-1β is controlled by the inflammasome. In this study, we addressed the mechanism underlying HS activation of the inflammasome in lung EC. We show that high mobility group box 1 acting through TLR4, and a synergistic collaboration with TLR2 and receptor for advanced glycation end products signaling, mediates HS-induced activation of EC NAD(P)H oxidase. In turn, reactive oxygen species derived from NAD(P)H oxidase promote the association of thioredoxin-interacting protein with the nucleotide-binding oligomerization domain-like receptor protein NLRP3 and subsequently induce inflammasome activation and IL-1β secretion from the EC. We also show that neutrophil-derived reactive oxygen species play a role in enhancing EC NAD(P)H oxidase activation and therefore an amplified inflammasome activation in response to HS. The present study explores a novel mechanism underlying HS activation of EC inflammasome and thus presents a potential therapeutic target for SIRS and ALI induced after HS.     

Promotion of the Clostridium acetobutylicum ATCC 824 growth and acetone–butanol–ethanol fermentation by flavonoids

An unexpected promotion effect of Ginkgo leaf on the growth of Clostridium acetobutylicum ATCC 824 and acetone–butanol–ethanol (ABE) fermentation was investigated. Component analysis of Ginkgo leaf was carried out and flavonoids were determined as the potential key metabolites. Then the flavonoids feeding experiments were carried out. Results showed that addition of only 10 mg/L flavonoids to the fermentation broth can promote butanol and ABE titre up to 14.5 and 17.8 g/L after 5 days of fermentation, that is, 74 and 68 % higher than the control. A 2.2-fold biomass also has been achieved. Furthermore, by employing such novel founding, we easily exploited flavonoids from soybean and some agriculture wastes as the wide-distributed and economic feasible ABE fermentation promoter. The mechanism of the above effects was investigated from the perspective of oxidation–reduction potential. This work opens a new way in the efforts to increase the titer of butanol.     

A Highly Efficient Gene Expression Programming (GEP) Model for Auxiliary Diagnosis of Small Cell Lung Cancer

Background

Lung cancer is an important and common cancer that constitutes a major public health problem, but early detection of small cell lung cancer can significantly improve the survival rate of cancer patients. A number of serum biomarkers have been used in the diagnosis of lung cancers; however, they exhibit low sensitivity and specificity.

Methods

We used biochemical methods to measure blood levels of lactate dehydrogenase (LDH), C-reactive protein (CRP), Na⁺, Cl^-, carcino-embryonic antigen (CEA), and neuron specific enolase (NSE) in 145 small cell lung cancer (SCLC) patients and 155 non-small cell lung cancer and 155 normal controls. A gene expression programming (GEP) model and Receiver Operating Characteristic (ROC) curves incorporating these biomarkers was developed for the auxiliary diagnosis of SCLC.

Results

After appropriate modification of the parameters, the GEP model was initially set up based on a training set of 115 SCLC patients and 125 normal controls for GEP model generation. Then the GEP was applied to the remaining 60 subjects (the test set) for model validation. GEP successfully discriminated 281 out of 300 cases, showing a correct classification rate for lung cancer patients of 93.75% (225/240) and 93.33% (56/60) for the training and test sets, respectively. Another GEP model incorporating four biomarkers, including CEA, NSE, LDH, and CRP, exhibited slightly lower detection sensitivity than the GEP model, including six biomarkers. We repeat the models on artificial neural network (ANN), and our results showed that the accuracy of GEP models were higher than that in ANN. GEP model incorporating six serum biomarkers performed by NSCLC patients and normal controls showed low accuracy than SCLC patients and was enough to prove that the GEP model is suitable for the SCLC patients.

Conclusion

We have developed a GEP model with high sensitivity and specificity for the auxiliary diagnosis of SCLC. This GEP model has the potential for the wide use for detection of SCLC in less developed regions.     

数字PCR仪校准方法研究

数字PCR仪是核酸绝对定量的重要仪器,因此确保数字PCR仪检测结果的准确性十分重要。通过对国内市场上数字PCR仪的比较分析,剖析了数字PCR仪的性能指标,对数字PCR仪的校准方法进行了探讨,设定了拷贝数浓度相对示值误差、拷贝数浓度重复性、荧光通道一致性和反应单元个数重复性作为数字PCR仪整机校准的计量技术指标,采用具有溯源性的国家有证标准物质,对方法进行了试验验证。验证结果表明了校准思路和方法的可行性,该方法操作性强,能够满足仪器技术要求以及用户需求, 提高了数字PCR仪检测结果的准确性和可靠性,对进一步拓展和深化数字PCR 技术的应用具有积极的促进作用。