Statistical Inference Methods for Two Crossing Survival Curves: A Comparison of Methods

A common problem that is encountered in medical applications is the overall homogeneity of survival distributions when two survival curves cross each other. A survey demonstrated that under this condition, which was an obvious violation of the assumption of proportional hazard rates, the log-rank test was still used in 70% of studies. Several statistical methods have been proposed to solve this problem. However, in many applications, it is difficult to specify the types of survival differences and choose an appropriate method prior to analysis. Thus, we conducted an extensive series of Monte Carlo simulations to investigate the power and type I error rate of these procedures under various patterns of crossing survival curves with different censoring rates and distribution parameters. Our objective was to evaluate the strengths and weaknesses of tests in different situations and for various censoring rates and to recommend an appropriate test that will not fail for a wide range of applications. Simulation studies demonstrated that adaptive Neyman’s smooth tests and the two-stage procedure offer higher power and greater stability than other methods when the survival distributions cross at early, middle or late times. Even for proportional hazards, both methods maintain acceptable power compared with the log-rank test. In terms of the type I error rate, Renyi and Cramér—von Mises tests are relatively conservative, whereas the statistics of the Lin-Xu test exhibit apparent inflation as the censoring rate increases. Other tests produce results close to the nominal 0.05 level. In conclusion, adaptive Neyman’s smooth tests and the two-stage procedure are found to be the most stable and feasible approaches for a variety of situations and censoring rates. Therefore, they are applicable to a wider spectrum of alternatives compared with other tests.     

A study of the genetic polymorphism of human inter-alpha-trypsin-inhibitor (ITI) in the Han population,Chengdu, China

Phenotypes of inter-alpha-trypsin-inhibitor (ITI) have been determined by isoelectric focusing on polyacrylamide gels followed by immunofixation. The phenotype frequencies of ITI in the Han population in Chengdu, P. R. China have been investigated using this method. In addition, family studies have been conducted in 21 families. The results show that ITI is polymorphic in the Han population in Chengdu, China. The allele frequencies are as follows: ITI*1 = 0.5763. ITI*2 = 0.4107, ITI*3 = 0.0130. ITI is thus a new and promising genetic marker that can be used in the field of forensic haematogenetics.     

四川雅安常见住区蝇类密度监测

根据全国常见住区蝇类密度监测课题组关于“全国常见住区蝇类密度监测实施计划”安排,雅安地区定力全国七个监测点之一,作者承担了这一任务。该项工作尚在继续进行中,现将1988年监测结果报道如下。     

Extracellular Dopamine, Norepinephrine, and Serotonin in the Nucleus Accumbens of Freely Moving Rats During Intracerebral Dialysis with Cocaine and Other Monoamine Uptake Blockers

Abstract: Monoamine-uptake blockers were applied focally (0.1–1,000 µ M ) through a dialysis probe in the nucleus accumbens of freely moving rats, and the extracellular concentrations of dopamine, norepinephrine, and serotonin were measured. The selective dopamine-uptake blocker GBR 12935 increased dopamine preferentially with only a small effect on norepinephrine, whereas the selective serotonin-uptake blocker fluoxetine increased serotonin output preferentially. In contrast, the selective norepinephrine-uptake blockers desipramine and nisoxetine enhanced not only norepinephrine, but also serotonin and dopamine appreciably. Cocaine increased all three amines with the greatest effects on dopamine and serotonin. As in our previous study on the ventral tegmental area, there was a positive association between dopamine and norepinephrine output when all blocker data were taken together. The present results suggest a contribution of the increase in norepinephrine, but not serotonin, to the enhancement of dopamine after cocaine applied focally in the nucleus accumbens.     

Protein factors that bind to the murine 2',5'-oligoadenylate synthetase ME-12 gene 5' upstream regulatory region

The murine 2',5'-oligoadenylate synthetase ME-12 gene regulatory region AB forms six complexes with protein factors in murine BALB/c 3T3 cells as demonstrated by the mobility shift electrophoresis assay under the reaction conditions used. The complexes, designated C1-C6 in order of their decreasing electrophoretic mobility, showed three distinctive specificities with regulatory region AB, element A, and element B as probes or competing DNA: 1) C1 is region AB-specific (this complex did not form with either element A or B used alone or as a mixture); 2) C5 formed both with element A and element B; 3) C2, C3, C4, and C6 formed with element B, but not A. The protein factors that give rise to these complexes show differential DNA binding activities in various buffer solutions at different pH values. The C4-forming protein factor is the interferon (IFN)-alpha/beta-stimulated response factor (ISRF) which shows element B specificity. It preexists in the cytoplasm. ISRF appears to be complexed to an inhibitor (ISRFI) in the cytoplasm and to dissociate from the inhibitor and to translocate into the nucleus upon treatment of cells with IFN-alpha/beta. We propose that IFN-alpha/beta treatment of BALB/c 3T3 can trigger at least two events: 1) loosening of a tight inhibitor-ISRF complex with the release of free ISRF; this may be mediated via phosphorylation of ISRF or ISRFI; 2) translocation of ISRF into the nucleus and binding to the enhancer element B, which results in the activation of 2',5'-oligoadenylate synthetase gene expression.     

Comparative Analysis of Endogenous Hormones and Metabolite Profiles in Early-Spring Flowering Plants and Unflowered Plants Revealing the Strategy of Blossom

Journal of Plant Growth Regulation - Early-spring plants are a special type of plant that complete their life cycle promptly in cold, early spring. Very little effort has been made into researching...     

Detection of quercetin based on Al-amplified phosphorescence signals of manganese-doped ZnS quantum dots

A simple phosphorescence method is proposed for quercetin detection based on Al³⁺-amplified room-temperature phosphorescence (RTP) signals of 3-mercaptopropionic acid (MPA)-capped Mn-doped ZnS quantum dots (QDs). The sensor was established based on some properties as follows. Al³⁺ can interact with carboxyl groups on the surface of MPA-capped Mn-doped ZnS QDs via chelation, which will lead to the aggregation of QDs and amplification of RTP signals, After the addition of quercetin, it can form more stable complex with Al³⁺ in alkaline aqueous solution and dissociate Al³⁺ from the surface of Mn-doped ZnS QDs, which will result in significant recovery of RTP intensity of the MPA-capped Mn-doped ZnS–Al³⁺ system. Under the optimized conditions, the change of RTP intensity was proportional to the concentration of quercetin in the range from 0.1 to 6.0 mg L⁻¹, with a high correlation coefficient of 0.996 and a detection limit of 0.047 mg L⁻¹. The proposed method is potentially suitable for detection of quercetin in real samples without complicated pretreatment.     

Tongxinluo Protects against Hypertensive Kidney Injury in Spontaneously-Hypertensive Rats by Inhibiting Oxidative Stress and Activating Forkhead Box O1 Signaling

Hypertension is an independent risk factor for the progression of chronic renal failure, and oxidative stress plays a critical role in hypertensive renal damage. Forkbox O1(FoxO1) signaling protects cells against oxidative stress and may be a useful target for treating oxidative stress-induced hypertension. Tongxinluo is a traditional Chinese medicine with cardioprotective and renoprotective functions. Therefore, this study aimed to determine the effects of Tongxinluo in hypertensive renal damage in spontaneously hypertensive rats(SHRs)and elucidate the possible involvement of oxidative stress and FoxO1 signaling in its molecular mechanisms. SHRs treated with Tongxinluo for 12 weeks showed a reduction in systolic blood pressure. In addition to increasing creatinine clearance, Tongxinluo decreased urinary albumin excretion, oxidative stress injury markers including malondialdehyde and protein carbonyls, and expression of nicotinamide adenine dinucleotide phosphate oxidase subunits and its activity in SHR kidneys. While decreasing phosphorylation of FoxO1, Tongxinluo also inhibited the phosphorylation of extracellular signal-regulated kinase1/2 and p38 and enhanced manganese superoxide dismutase and catalase activities in SHR kidneys. Furthermore, histology revealed attenuation of glomerulosclerosis and renal podocyte injury, while Tongxinluo decreased the expression of α-smooth muscle actin, extracellular matrixprotein, transforming growth factor β1 and small mothers against decapentaplegic homolog 3,and improved tubulointerstitial fibrosis in SHR kidneys. Finally, Tongxinluo inhibited inflammatory cell infiltration as well as expression of tumor necrosis factor-α and interleukin-6. In conclusion, Tongxinluo protected SHRs against hypertension-induced renal injury by exerting antioxidant, antifibrotic, and anti-inflammatory activities. Moreover, the underlying mechanisms of these effects may involve inhibition of oxidative stress and functional activation of FoxO1 signaling.