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Purpose@#This study aimed to explore the impact of ABL1–tyrosine kinase inhibitors (TKIs) adherence on the survival of chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) children and clarify the potential predictors of patients’ prognosis from TKIs intake practices. @*Materials and Methods@#Ninety newly diagnosed Ph+ ALL patients who received TKIs were enrolled. We collected the baseline characteristics and adverse events in all children; moreover, TKIs adherence was measured by an eight-item Morisky medication adherence scale (MMAS-8). Progression-free survival (PFS) and overall survival (OS) analysis were performed, and risk factors for PFS and OS were evaluated. @*Results@#Among all patients, 69 cases were regarded as adherers, while 21 were non-adherers. The median duration of TKIs interruption was significantly prolonged in the non-adherence group than in the adherence group (13 [0-101] vs. 56 [11-128], p < 0.001). Additionally, dose reduction occurred in 55.2% of non-adherers versus 23.0% of adherers (p=0.002). The PFS and OS in adherers were significantly higher versus non-adherers (p=0.020 and p=0.039). MMAS-8 score was an independent risk factor for PFS (p=0.010) and OS (p=0.031). Among non-adherers, the median OS was only 23.1% (4.2%-42%) in patients aged ≤ 10 years versus 54.4% (38.8%-70%) in adolescents. Most of the patients who experienced TKIs non-adherence suffered pancytopenia. @*Conclusion@#TKIs adherence during treatment significantly influenced the survival of pediatric Ph+ ALL patients, and non-adherers with age ≤ 10 years were more vulnerable to TKIs disruption. The cumulative TKIs dose should be especially emphasized to patients with age ≤ 10 years, which may result in an inferior achievement of relevant treatment milestones.
ABSTRACT
Objective: To carry out the studies of pharmacological action for extracts of Aconiti Radix and Aconiti Radix Cocta, and evaluate the selection of raw materials in prescriptions, in order to promote the development and clinical application of preparations. Method: The mixed extracts of Aconiti Radix and Aconiti Radix Cocta were prepared respectively according to the technique of aconitum injection, and different dose groups of Aconiti Radix and Aconiti Radix Cocta were established based on the dose of Aconiti Radix 0.152 5 mg·g-1, and then applied in such pharmacodynamic tests as analgesia, heart rate reduction, antitumor effect and toxicology tests, such as acute toxicity and organ observation. The data were analyzed systematically on the basis of literatures. Result: Compared with blank group, the extracts of both Aconiti Radix and Aconiti Radix Cocta had a significantly analgesic effect. At the same dose, the pain inhibition rate of Aconiti Radix injection (60.91%) was higher than that of Aconiti Radix Cocta injection (53.42%), and the pain inhibition rate of Aconiti Radix extract for oral administration(73.94%) was also much higher than that of Aconiti Radix Cocta extract (29.97%), with significant differences (Pth min after administration, the heart rate of the Aconiti Radix group was decreased first, then stabilized, and finally increased with the rise of the dose, while for the Aconiti Radix Cocta group showed a different trend of first stability, then decrease and finally increase. The result indicated the Aconiti Radix group had the effect in reducing heart rate in rats at a low dose. The survival inhibition rate was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The extracts of both Aconiti Radix and Aconiti Radix Cocta had a significantly inhibitory effect on the proliferation of AGS gastric cancer cells, in which Aconiti Radix was stronger than that of Aconiti Radix Cocta at the same dose. In the acute toxicity test of rats, lethal dose 50%(LD50) of Aconiti Radix and Aconiti Radix Cocta were 3.9 g·kg-1 and 21.0 g·kg-1 respectively, which were equivalent to 4 times and 20 times of the clinical dose. LD50 of the extract of Aconiti Radix Cocta was 5 times than that of Aconiti Radix. The liver and kidney of dead rats were dark with obvious symptoms of poisoning after dissection, while all the organs of rats at the clinical and lower dose were normal. Conclusion: The safety of Aconiti Radix is lower than that of Aconiti Radix Cocta, but with greater analgesic, bradycardic and anticancerous effect. Therefore, it is suggested that the preparations, such as aconitum injection, should be prepared with Aconiti Radix in the treatment of severe pain of patients with advanced gastric and liver cancer, and the preparations for general pain can be prepared with Aconiti Radix Cocta, so as to achieve a truly safe and effective dialectical treatment.
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<p><b>OBJECTIVE</b>To construct mouse enhanced green fluorecence protein (EGFP) -peroxisome proliferator-activated receptor (PPAR)gamma2, and to detect EGFP-PPARgamma2 expression in infected mouse bone marrow mesenchymal stem cells (BMSC).</p><p><b>METHODS</b>Cut the fragment of PPARgamma2 from the expression plasmid pcDNA flag PPARgamma2, then cloned the gene fragment into pEGFP-C1 and pEGFP-N1 vector. Subsequently, subclone the fragment EGFP-PPARgamma2 from pEGFP-C1-PPARgamma2 into the shuttle plasmid DC315. HEK293 cells were co-transfected with the constructed recombinant shuttle plasmid DC315-EGFP-PPARgamma2 and large adenovirus helper plasmid pBHGlox deltaE1, 3Cre in mediation of liposome. The obtained replication-defective recombinant adenovirus Ad-EGFP-PPARgamma2 was confirmed. Then it was propagated in HEK293 cells. After the BMSC were transfected for 72 h, adipogenic differentiation was demonstrated.</p><p><b>RESULTS</b>HEK293 cells were transfected with the pEGFP-C1-PPARgamma2 or pEGFP-N1-PPARgamma2 in mediation of liposome. The former green fluorescence protein was better than the latter by fluorescence microscope. The recombinant plasmids were digested and identified. Western blot analysis showed the expression of EGFP-PPARgamma2 in vitro. EGFP-PPARgamma2 protein was detectable in the nucleus of BMSC.</p><p><b>CONCLUSION</b>The recombinant adenovirus encoding EGFP-PPARgamma2 fusion protein was successfully constructed, which provided a basis for application of EGFP-PPARgamma2 gene to adenovirus-mediated gene therapy.</p>
Subject(s)
Animals , Humans , Mice , Adenoviridae , Bone Marrow Cells , Metabolism , Genetic Vectors , Green Fluorescent Proteins , Metabolism , HEK293 Cells , Mesenchymal Stem Cells , Metabolism , PPAR gamma , Metabolism , Recombinant Proteins , Metabolism , TransfectionABSTRACT
<p><b>OBJECTIVE</b>To investigate the treatment of perioperative period on maxillofacial patients with diabetes.</p><p><b>METHODS</b>The retrospective analysis was taken on clinical data of 24 cases of maxillofacial patients with diabetes.</p><p><b>RESULTS</b>All patients recovered without severe complications by controlling blood sugar during whole stage and preventing infection with antibiotics after surgery. The wounds in 21 cases healed in 10-14 days after the operations and that didn't in 3 cases. With the treatment on local wounds, the wounds in 3 cases healed in 14-28 days after the operations.</p><p><b>CONCLUSION</b>It's the treatment principle of maxillofacial surgical patients with diabetes to monitor the levels of blood glucose on time, to control the levels of blood glucose rigorously at the whole stage and to prevent complication.</p>