Estimating incremental cost-effectiveness ratios and their confidence intervals with differentially censored data

With medical costs escalating over recent years, cost analysis is being conducted more and more to assess economic impact of new treatment options. An incremental cost-effectiveness ratio (ICER) is a measure that assesses the additional cost for a new treatment for each additional unit of effectiveness, such as saving 1 year of life. In this article, we consider cost-effectiveness analysis for new treatments evaluated in a randomized clinical trial setting with staggered entries. In particular, the censoring times are different for cost and survival data. We propose a method for estimating the ICER and obtaining its confidence interval when differential censoring exists. Simulation experiments are conducted to evaluate our proposed method. We also apply our methods to a clinical trial example comparing the cost-effectiveness of implanted defibrillators with conventional therapy for individuals with reduced left ventricular function after myocardial infarction.     

Preparation of konjac glucomannan hydrogels as DNA-controlled release matrix

In this study, hydrogels for DNA-controlled release was prepared with konjac glucomannan (KGM), a water-soluble non-ionic polysaccharide, by means of deacetylated reaction and physically cross-linking method under mild conditions. The properties of the KGM hydrogels were analyzed by FTIR spectra and scanning electron microscopy (SEM). The integrality of the released DNA was investigated by circular dichroism (CD). The DNA release kinetics was performed using the DNA-loaded KGM gels in buffer solutions of pH 7.4 at 37+/-0.5 degrees C. Peppas model and Higuchi model were used to analysis the DNA release mechanism; the data indicated that the DNA release can be controlled by changing the preparation conditions and the structure parameters of the gels. This study suggested that the KGM hydrogels have a potential use for advanced controlled release.     

温度对圆尾肖蛸个体发育和繁殖力的影响

圆尾肖蛸(Tetragnotha vermiformis)在我国广泛分布于棉田、稻田、森林、果园。该蜘蛛具有捕食多种农作物害虫的能力,在湖堤、河岸、沟边更是蚊虫的有效天敌。本文仅就圆尾肖蛸的历期和繁殖力与温度的关系方面的试验结果进行了整理,并力图建立相应的数学模型,旨在为保护和利用工作提供科学依据。     

Oxalate production at different initial Pb²+ concentrations and the influence of oxalate during solid-state fermentation of straw with Phanerochaete chrysosporium

The production of oxalate at different initial Pb²⁺ concentrations during solid-state fermentation of straw with Phanerochaete chrysosporium was investigated. It was found that the maximal peak value of oxalate concentration (22.84 mM) was detected at the initial Pb²⁺ concentration of 200 mg kg⁻¹ dry straw, while the minimum (15.89 mM) at the concentration of 600 mg Pb²⁺ kg⁻¹ dry straw, and at moderate concentration of Pb²⁺ the capability of oxalic acid secretion was enhanced. In addition, it was also found that more oxalic acid accumulation went together with better Pb²⁺ passivation effect and higher manganese peroxidase (MnP) activity. The present findings will improve the understandings of the interactions of heavy metals with white-rot fungi and the role of oxalate in lignin degradation system, which could provide useful references for more efficient treatment of Pb-contaminated lignocellulosic waste.     

Comparative genomic analysis of the pPT23A plasmid family of Pseudomonas syringae

Members of the pPT23A plasmid family of Pseudomonas syringae play an important role in the interaction of this bacterial pathogen with host plants. Complete sequence analysis of several pPT23A family plasmids (PFPs) has provided a glimpse of the gene content and virulence function of these plasmids. We constructed a macroarray containing 161 genes to estimate and compare the gene contents of 23 newly analyzed and eight known PFPs from 12 pathovars of P. syringae, which belong to four genomospecies. Hybridization results revealed that PFPs could be distinguished by the type IV secretion system (T4SS) encoded and separated into four groups. Twelve PFPs along with pPSR1 from P. syringae pv. syringae, pPh1448B from P. syringae pv. phaseolicola, and pPMA4326A from P. syringae pv. maculicola encoded a type IVA T4SS (VirB-VirD4 conjugative system), whereas 10 PFPs along with pDC3000A and pDC3000B from P. syringae pv. tomato encoded a type IVB T4SS (tra system). Two plasmids encoded both T4SSs, whereas six other plasmids carried none or only a few genes of either the type IVA or type IVB secretion system. Most PFPs hybridized to more than one putative type III secretion system effector gene and to a variety of additional genes encoding known P. syringae virulence factors. The overall gene contents of individual PFPs were more similar among plasmids within each of the four groups based on T4SS genes; however, a number of genes, encoding plasmid-specific functions or hypothetical proteins, were shared among plasmids from different T4SS groups. The only gene shared by all PFPs in this study was the repA gene, which encoded sequences with 87 to 99% amino acid identityamong 25 sequences examined. We proposed a model to illustrate the evolution and gene acquisition of the pPT23A plasmid family. To our knowledge, this is the first such attempt to conduct a global genetic analysis of this important plasmid family.     

Analysis of protein fragmentation inhibition by an MMP-inhibitor in an in vivo model of heart failure using automated chromatography

Proteomic strategies have continued to demonstrate value in studying disease by exploiting new technologies that can develop significant numbers of measurements from single samples. However, using complex samples such as tissues or blood has continued to be problematic due to the presence of major interfering substances. In this study, a process is described that uses denaturing peptide extraction from whole tissue and automated chromatography in order to allow subsequent analysis of more than 1000 tissue-derived peptides per sample. The process was employed to identify cardiac proteins that were spared degradation by administration of a heart-protecting matrix metalloproteinase (MMP) inhibitor (compound SC-621) following experimental myocardial infarction (MI). HPLC peptide fingerprints were developed from rat heart left ventricles and the resultant integrated peak data was compared across experimental animals. Surprisingly, although protein fragmentation was generally increased in MI hearts, the effect of the MMP inhibitor was only observed on a few species. The results from this study demonstrated that whole-tissue sample enrichment and peptide analysis using HPLC could be linked in order to study the effects of new compounds on a disease state. The system is flexible and amenable to improvements such as incorporating detection by mass spectrometry.     

Identification of a D-amino acid decapeptide HIV-1 entry inhibitor

Entry of human immunodeficiency virus type 1 (HIV-1) virion into host cells involves three major steps, each being a potential target for the development of entry inhibitors: gp120 binding to CD4, gp120-CD4 complex interacting with a coreceptor, and gp41 refolding to form a six-helix bundle. Using a D-amino acid decapeptide combinatorial library, we identified peptide dC13 as having potent HIV-1 fusion inhibitory activity, and effectively inhibiting infection by several laboratory-adapted and primary HIV-1 strains. While dC13 did not block binding of gp120 to CD4, nor disrupt the gp41 six-helix bundle formation, it effectively blocked the binding of an anti-CXCR4 monoclonal antibody and chemokine SDF-1alpha to CXCR4-expressing cells. However, because R5-using primary viruses were also neutralized, the antiviral activity of dC13 implies additional mode(s) of action. These results suggest that dC13 is a useful HIV-1 coreceptor antagonist for CXCR4 and, due to its biostability and simplicity, may be of value for developing a new class of HIV-1 entry inhibitors.     

Alisol A attenuates high‐fat‐diet‐induced obesity and metabolic disorders via the AMPK/ACC/SREBP‐1c pathway

Obesity and its associated metabolic disorders such as diabetes, hepatic steatosis and chronic heart diseases are affecting billions of individuals. However there is no satisfactory drug to treat such diseases. In this study, we found that alisol A, a major active triterpene isolated from the Chinese traditional medicine Rhizoma Alismatis, could significantly attenuate high‐fat‐diet‐induced obesity. Our biochemical detection demonstrated that alisol A remarkably decreased lipid levels, alleviated glucose metabolism disorders and insulin resistance in high‐fat‐diet‐induced obese mice. We also found that alisol A reduced hepatic steatosis and improved liver function in the obese mice model.In addition, protein expression investigation revealed that alisol A had an active effect on AMPK/ACC/SREBP‐1c pathway. As suggested by the molecular docking study, such bioactivity of alisol A may result from its selective binding to the catalytic region of AMPK.Therefore, we believe that Alisol A could serve as a promising agent for treatment of obesity and its related metabolic diseases.