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Abstract Background Oral prednisone has been recognized as the first-line therapy for the treatment of ocular myasthenia gravis (OMG). However, its long-term use is complicated by numerous adverse effects and is ineffective for some OMG patients in reaching remission. This study aimed to evaluate the effectiveness and safety of intravenous methylprednisolone (IVMP) and tacrolimus monotherapy for OMG patients with unsatisfactory responses to conventional prednisone therapy. Methods We retrospectively reviewed 57 OMG patients who had not achieved satisfactory improvement after prednisone therapy and thereby received IVMP or tacrolimus monotherapy for at least 6 months. Ocular symptoms were evaluated by the ocular-quantitative MG (QMG) score at each time point. A ≥ 2-point fall in ocular QMG score was defined as the cut-off point to indicate clinical improvement. Logistic regression analysis was performed to identify factors associated with the efficacy of IVMP at discharge. Adverse events were recorded. Results Both IVMP and tacrolimus monotherapy demonstrated significant clinical efficacy, with no statistical differences observed at the study endpoint. The proportions of patients who reached the cut-off point for efficacy evaluation were higher in the IVMP group than in the tacrolimus group (1, 3, and 6 months: 51.7% (15/29) vs 12.0% (3/25), p = 0.002; 69.0% (20/29) vs 40.0% (10/25), p = 0.033; 69.0% (20/29) vs 46.4% (13/28), p = 0.085, respectively). Multivariate logistics analysis showed that high ocular QMG scores at baseline indicated favourable responses to IVMP treatment (OR = 1.781; 95% CI 1.066–2.975; p = 0.028). All the adverse events were transient and tolerable. Conclusion Our findings suggest that both IVMP and tacrolimus monotherapy hold promise as viable treatment options for OMG patients with unsatisfactory responses to oral prednisone. The study supports the safety and effectiveness of both therapies, with IVMP exhibiting faster improvement and favourable efficacy in patients with high ocular QMG scores.

Background: Overexpression of cyclin D1 dependent kinases 4 and 6 (CDK4/6) is a common feature of many human cancers including leukemia. LEE011 is a novel inhibitor of both CDK4 and 6. To date, the molecular function of LEE011 in leukemia remains unclear. Methods: Leukemia cell growth and apoptosis following LEE011 treatment was assessed through CCK-8 and annexin V/propidium iodide staining assays. Cell senescence was assessed by β-galactosidase staining and p16INK4a expression analysis. Gene expression profiles of LEE011 treated HL-60 cells were investigated using an Arraystar Human LncRNA array. Gene ontology and KEGG pathway analysis were then used to analyze the differentially expressed genes from the cluster analysis. Results: Our studies demonstrated that LEE011 inhibited proliferation of leukemia cells and could induce apoptosis. Hoechst 33,342 staining analysis showed DNA fragmentation and distortion of nuclear structures following LEE011 treatment. Cell cycle analysis showed LEE011 significantly induced cell cycle G1 arrest in seven of eight acute leukemia cells lines, the exception being THP-1 cells. β-Galactosidase staining analysis and p16INK4a expression analysis showed that LEE011 treatment can induce cell senescence of leukemia cells. LncRNA microarray analysis showed 2083 differentially expressed mRNAs and 3224 differentially expressed lncRNAs in LEE011-treated HL-60 cells compared with controls. Molecular function analysis showed that LEE011 induced senescence in leukemia cells partially through downregulation of the transcriptional expression of MYBL2. Conclusions: We demonstrate for the first time that LEE011 treatment results in inhibition of cell proliferation and induction of G1 arrest and cellular senescence in leukemia cells. LncRNA microarray analysis showed differentially expressed mRNAs and lncRNAs in LEE011-treated HL-60 cells and we demonstrated that LEE011 induces cellular senescence partially through downregulation of the expression of MYBL2. These results may open new lines of investigation regarding the molecular mechanism of LEE011 induced cellular senescence. [ABSTRACT FROM AUTHOR]

Zinc finger protein (ZFP) genes comprise a large and diverse gene family, and are involved in biotic and abiotic stress responses in plants. In this study, a total of 126 ZFP genes classified into various types in wheat were characterized and subjected to expression pattern analysis under inorganic phosphate (Pi) deprivation. The wheat ZFP genes and their corresponding GenBank numbers were obtained from the information of a 4×44K wheat gene expression microarray chip. They were confirmed by sequence similarity analysis and named based on their homologs in Brachypodium distachyon or Oriza sativa. Expression analysis based on the microarray chip revealed that these ZFP genes are categorized into 11 classes according to their gene expression patterns in a 24-h of Pi deprivation regime. Among them, ten genes were differentially up-regulated, ten genes differentially down-regulated, and two genes both differentially up- and down-regulated by Pi deprivation. The differentially up- or down-regulated genes exhibited significantly more or less transcripts at one, two, or all of the checking time points (1, 6, and 24 h) of Pi stress in comparison with those of normal growth, respectively. The both differentially up- and down-regulated genes exhibited contrasting expression patterns, of these, TaWRKY70;5 showed significantly up-regulated at 1 and 6 h and down-regulated at 24 h whereas TaAN1AN20-8;2 displayed significantly upregulated at 1 h and downregulated at 6 h under deprivation Pi condition. Real time PCR analysis confirmed the expression patterns of the differentially expressed genes obtained by the microarray chip. Our results indicate that numerous ZFP genes in wheat respond to Pi deprivation and have provided further insight into the molecular basis that plants respond to Pi deprivation mediated by the ZFP gene family.

The partial and complete periodic synchronization in coupled discontinuous map lattices consisting of both discontinuous and non-invertible maps are discussed. We classify three typical types of periodic synchronization states, which give rise to different spatiotemporal patterns including static partial periodic synchronization, dynamically periodic synchronization, and complete periodic synchronization patterns. A special prelude dynamics of partial and complete periodic synchronization motion, which is shown by five separated concave curves in the time series plots of the order parameters, is observed. The detailed analysis shows that the special prelude dynamics is induced by the competition between two synchronized clusters, and the analytical expression for the corresponding order parameter is obtained. [ABSTRACT FROM AUTHOR]

Objective To evaluate 4Rs principle applied in animal experiments for research and to optimize training outcomes with animal model. Methods The 4Rs principle was applied in four parts of training process with animal models including “replacing animal experiments with human physiological experiments” “integrating experimental projects, reducing the use of animals” “optimizing experimental process for minimizing animal suffering” and “strengthening ethical concepts, responsibility in research with experimental animals”. After class, feedbacks from students were collected through questionnaire survey and the data was analyzed. Results There were 92.0% medical students showed sympathize for the laboratory animals in the process of animal experiments; took care of the welfare of experimental animals while achieving training objectives. Conclusions The 4Rs principle provides a new idea and method for animal experiment and cultivates learners' animal ethics.