D-optimal designs formulti-response linear mixed models

Linear mixed models have become popular in many statistical applications duringrecent years. However design issues for multi-response linear mixed models are rarelydiscussed. Themain purpose of this paper is to investigate D-optimal designs formultiresponselinear mixed models. We provide two equivalence theorems to characterizethe optimal designs for the estimation of the fixed effects and the prediction of randomeffects, respectively. Two examples of the D-optimal designs formulti-response linearmixed models are given for illustration

Development of small interfering RNA delivery system using PEI-PEG-APRPG polymer for antiangiogenic vascular endothelial growth factor tumor-targeted therapy

Zong-Xia Lu1, Li-Ting Liu1,2, Xian-Rong Qi11Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China; 2Department of Pharmacy, School and Hospital of Stomatology, Peking University, Beijing, People's Republic of ChinaBackground: Small interfering RNA (siRNA) can silence target genes in the cytoplasm and be a major tool in gene therapy. Vascular endothelial growth factor (VEGF), a potent regulator of angiogenesis, is overexpressed in most tumors and is closely associated with tumor growth and metastasis. It has been shown that inhibition of VEGF expression by siRNA is an effective and useful method for antiangiogenic tumor therapy.Methods: In the present study, we synthesized a targeted delivery system of PEI-PEG-APRPG incorporating angiogenic vessel-homing Ala-Pro-Arg-Pro-Gly (APRPG) peptide into cationic polyethylenimine (PEI) via a hydrophilic poly(ethylene glycol) (PEG) spacer.Results: PEI-PEG-APRPG effectively condensed siRNA into 20–50 nm nanoparticles with a positive surface charge using a suitable N/P ratio. The siRNA/PEI-PEG-APRPG complex effectively enhanced the stability of siRNA in RNase A, and improved the proliferation-inhibiting ability and transfection efficiency of siRNA in vitro and tumor accumulation in vivo. In addition, the siRNA/PEI-PEG-APRPG complex exhibited high efficiency as antitumor therapy with regard to tumor growth, microvessel density, and VEGF protein and mRNA levels.Conclusion: These findings suggest that PEI-PEG-APRPG effectively delivers siRNA to tumors overexpressing VEGF and thereby inhibits tumor growth.Keywords: PEI-PEG-APRPG, VEGF siRNA, gene delivery, tumor-targeted, antiangiogenic therap

Identification of metabolites of kurarinone from Sophora flavescens Ait in rat urine by ultra-performance liquid chromatography with linear ion trap orbitrap mass spectrometry

Purpose: To study the in vivo metabolism of kurarinone, a lavandulyl flavanone which is a major constituent of Kushen and a marker compound with many biological activities, using ultra-performance liquid chromatography coupled with linear ion trap Orbitrap mass spectrometry (UPLC-LTQ-Orbitrap-MS).Methods: Six male Sprague-Dawley rats were randomly divided into two groups. First, kurarinone was suspended in 0.5 % carboxymethylcellulose sodium  (CMC-Na) aqueous solution, and was given to rats (n = 3, 2 mL for each rat) orally at 50 mg/kg. A 2 mL aliquot of 0.5 % CMC-Na aqueous solution was administered to the rats in the control group. Next, urine samples were collected over 0-24 h after the oral administrations and all urine samples were pretreated by a solid phase extraction (SPE) method. Finally, all samples were analyzed by a UPLC-LTQ-Orbitrap mass spectrometry coupled with an electrospray ionization source (ESI) that was operated in the negative ionization mode.Results: A total of 11 metabolites, including the parent drug and 10 phase II metabolites in rat urine, were first detected and interpreted based on accurate mass measurement, fragment ions, and chromatographic retention times. The results were based on the assumption that kurarinone glucuronidation was the dominant  metabolite that was excreted in rat urine.Conclusion: The results from this work indicate that kurarinone in vivo is typically transformed to nontoxic glucuronidation metabolites, and these findings may help to characterize the metabolic profile of kurarinone.Keywords: Kurarinone, Metabolites, Sophora flavescens Ait., Glucuronidation metabolite

The truncated Milstein method for stochastic differential equations with commutative noise

Inspired by the truncated Euler-Maruyama method developed in Mao (J. Comput. Appl. Math. 2015), we propose the truncated Milstein method in this paper. The strong convergence rate is proved to be close to 1 for a class of highly non-linear stochastic differential equations with commutative noise. Numerical examples are given to illustrate the theoretical results

Investigation and analysis of planting varieties and qualities of high quality paddy in Guangxi

The planting varieties and qualities of 154 new high-quality paddy samples harvested in Guangxi in 2018 were investigated and analyzed in this paper. The results showed that abundant resources of high quality paddy varieties were planted in Guangxi, such as bai-xiang, silk fragrance, wild fragrance, oil percentage and silk seedlings. The food quality scores of the collected paddy samples all meet the requirement of grade III standard (≥70 points) specified in GB/T 17891—2017, 92.2% of the paddy samples could meet the requirement of grade II standard (≥80 points), and 9.7% of the paddy samples could meet the requirement of grade I standard (≥90 points). According to the requirements of high quality paddy amylose content (dry basis) range (14.0%~24.0%), 70.8% of the paddy samples could meet the requirements, and 29.2% of the total number of samples (45 paddy samples) was less than 14.0%, which did not meet the requirements of the standard, but 38 paddy samples of them could meet the requirement of grade II standard (≥80 points) specified in GB/T 17891—2017. The survey results showed that the whole quality of the newly harvested high quality paddy in Guangxi was excellent

Klinička primjena RT-PCR u otkrivanju DNK tuberkuloze u kombinaciji s TB-IGRA u dijagnostici plućne tuberkuloze s negativnim nalazom sputuma

The aim was to investigate detection of pulmonary alveolar lavage fluid tuberculosis DNA by real-time fluorescent polymerase chain reaction (RT-PCR) combined with clinical application of the sputum smear-negative pulmonary tuberculosis diagnosis with TB interferon-γ release assay (TB-IGRA). From October 2014 to October 2015, 632 outpatients and inpatients treated in our hospital were randomly selected, of which 459 patients as the research group managed with RT-PCR detection combined with TB-IGRA and 173 patients as the control group undergoing electronic bronchoscopy alveolar lavage fluid detection, with detection results statistically evaluated. The positive rate in the research group was 96.51%, i.e. significantly higher than that in the control group (66.47%), yielding a statistically significant difference (χ2=109.68, p=0.00). The true positive rate was 97.7% in the research group and 67.92% in the control group; the true positive rate was significantly higher in the research group patients as compared with the control group, yielding a statistically significant difference (χ2=112.04, p=0.00). The sensitivity and specificity, as well as Youden index were significantly higher in the research group as compared with the control group. In conclusion, TB DNA detection by RT-PCR combined with TB-IGRA is a very good method of diagnosing tuberculosis, and it can be implemented in clinical diagnosis of pulmonary tuberculosis.Cilj istraživanja bio je ispitati otkrivanje DNK tuberkuloze u plućnom alveolarnom ispirku pomoću lančane reakcije polimeraze u stvarnom vremenu s fluorescentnim bojama (RT-PCR) u kombinaciji s kliničkom primjenom dijagnostike plućne tuberkuloze s negativnim nalazom sputuma pomoću testa otpuštanja TB interferona-γ (TB-IGRA). Od listopada 2014. do listopada 2015. godine nasumce su odabrane 632 osobe bolnički i izvanbolnički liječene u našoj bolnici, od kojih je 459 uključeno u ispitnu skupinu podvrgnutu otkrivanju pomoću RT-PCR u kombinaciji s testom TB-IGRA, a 173 u kontrolnu skupinu podvrgnutu elektroničkom otkrivanju u bronhoskopskom alveolarnom ispirku; rezultati su statistički obrađeni. Stopa pozitivnih nalaza bila je 96,51% u ispitnoj skupini, odnosno značajno viša od one u kontrolnoj skupini (66,47%), uz statistički značajnu razliku (χ2=109,68; p=0,00). Stopa stvarno pozitivnih nalaza bila je 97,7% u ispitnoj skupini i 67,92% u kontrolnoj skupini, dakle značajno viša kod bolesnika ispitne skupine u usporedbi s kontrolnom skupinom, uz statistički značajnu razliku (χ2=112,04; p=0,00). Osjetljivost i specifičnost, kao i Youdenov indeks bili su značajno viši u ispitnoj skupini u usporedbi s kontrolnom skupinom. U zaključku, otkrivanje TB DNK pomoću RT-PCR u kombinaciji s TB-IGRA vrlo je dobra metoda za dijagnosticiranje tuberkuloze, koja se može primjenjivati u kliničkoj dijagnostici plućne tuberkuloze

Study on the spatial distribution pattern of Cx40 gap junctions in the atria of patients with coronary heart disease

Background: The aim of this study was to evaluate the association between atrial fibrillation and atrial dilation and the spatial distribution pattern of connexin 40 in the atria of patients with coronary heart disease. Methods: Twenty-six patients with coronary heart disease undergoing cardiac surgery for coronary artery bypass graft were investigated and were divided into three groups according to the left atrial size and rhythm, atrial fibrillation and left atrial dilatation (AF+AD), sinus rhythm and left atrial dilation (SR+AD) and sinus rhythm as control group SR. The spatial distribution patterns of Cx40 were evaluated using confocal laser scanning microscopy assay. Results: No significant differences were observed in the size and density of Cx40 gap junction in the right atrium among all three groups (p > 0.05). Compared with the control group, the size of Cx40 disk area in termination links and in lateral abutment in left atrium was markedly larger in AF+AD group and SR+AD group than those of the controls (p < 0.01). A comparison of size and density of Cx40 gap junction in the left atrium in the AF+AD group and SR+AD group did not show significant differences. Conclusions: The present study has shown altered gap junction distribution in coronary heart disease resulting from atrial dilation and atrial fibrillation. A decrease in the size and density of Cx40 gap junction was observed in patients with atrial dilation, which could be an important factor in the initiation and maintenance of atrial fibrillation. (Cardiol J 2008; 15: 50-56