The ABCG2 mRNA Synthesized in vitro Promoted Uric Acid Excretion in Mice / 中国生物化学与分子生物学报

Hyperuricemia is a chronic metabolic disease caused by the accumulation of uric acid in the body caused by purine metabolism disorder. In recent years, the incidence of hyperuricemia has increased and the age of onset is showing a younger trend. Finding effective therapeutic targets and treatment methods is a hot spot of current research. The urate transporter ATP-binding cassette subfamily G member 2 (ABCG2) is mainly expressed in the kidney and promotes uric acid excretion. In this study, ABCG2 mRNA was synthesized in vitro and transfected into hyperuricemia model mice to observe its effect on mouse uric acid levels. Firstly, the DNA template of ABCG2 mRNA was chemically synthesized, and then transcribed into mRNA in vitro, followed by modification and transfection into mouse TCMK-1 renal tubular epithelial cells. Finally, the protein expression in the cells was detected by Western blot. The results showed that the amount of protein expression in TCMK-1 cells was positively correlated with the amount of transfected mRNA (P < 0. 01), indicating a successful transfection. In animal experiments, twenty-four SPF mice were randomly divided into four groups (n = 6): control group, hyperuricemia model group, benzbromarone group [20 mg/(kg•d)] and mRNA group [2 mg/(kg•3d)]. The mice have been modeled and treated for 28 days. During this period, the body weight and growth status of the mice were monitored daily. After the treatment, the levels of serum uric acid, urine uric acid, serum creatinine, blood urea nitrogen and liver xanthine oxidase were analyzed. The results showed that compared with the model group of mice, mRNA treatment can significantly reduce the levels of serum uric acid (100. 38 ± 10. 94), blood urea nitrogen (6. 30 ± 1. 10), and serum creatinine (30. 86 ± 5. 78, P<0. 05 or P<0. 01). It can also increase the level of urine uric acid (617. 48 ± 50. 34, P<0. 05) in mice and promote the excretion of uric acid. But it has no significant effect on the activity of xanthine oxidase (26. 19 ± 2. 58) in the liver. The pathological changes of mice kidney were observed by HE staining. The results showed that compared with mice in the model group, pathological damages such as renal tubular cell edema and inflammatory cell infiltration in the mRNA treatment group were significantly improved. The relative expression of mRNA in mice kidney was detected by qRT-PCR, and the protein expression of ABCG2 in mice kidney was detected by immunohistochemistry and Western blot. The results showed that the relative expression of ABCG2 mRNA and its protein were significantly up-regulated in the kidney tissues of mice in the mRNA group (P < 0. 01), indicating that the transfection was successful in vivo. In conclusion, ABCG2 mRNA synthetized and modified in vitro can be successfully expressed in hyperuricemia mice and promote excretion of uric acid and other organic ions, as well as improvement of renal injury in mice. These results provide experimental basis for the clinical application of ABCG2 as a target for the treatment of hyperuricemia related diseases.

Therapeutic effects of different drug regimens and metabolic markers in children with bipolar affective disorder: a comparative analysis / 中国当代儿科杂志

OBJECTIVE@#To study the changes in metabolic markers and clinical outcome after treatment with different drug regimens in children with bipolar affective disorder.@*METHODS@#A retrospective analysis was performed on the medical data of 220 children with bipolar affective disorder who attended the hospital from January 2017 to January 2020. According to the treatment method, 112 children treated with atypical antipsychotic drugs alone were enrolled as the control group, and 108 children treated with atypical antipsychotic drugs combined with mood stabilizer were enrolled as the study group. The two groups were compared in terms of baseline data, changes in related metabolic markers[fasting insulin (FIN), glycosylated hemoglobin (HbAlc), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)] after treatment, incidence rate of metabolic syndrome, and clinical outcome.@*RESULTS@#There were no significant differences in the baseline data including age, sex, and course of disease between the two groups (@*CONCLUSIONS@#Atypical antipsychotic drugs combined with mood stabilizer in the treatment of bipolar disorder in children have little effect on the level of metabolic markers, and the curative effect is significant.

Prognostic value of ventricular longitudinal systolic velocities and maximal oxygen consumption in patients with dilated cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the prognostic value of regional longitudinal ventricular systolic velocities with that of maximal oxygen consumption (VO(2max)) in patients with dilated cardiomyopathy (DCM).</p><p><b>METHODS</b>VO(2max) derived from cardiopulmonary exercise tests and regional longitudinal ventricular systolic velocities obtained from tissue Doppler imaging were compared in 18 DCM patients with cardiac events (death, cardiac transplantation, hospitalization, group A) and 24 patients without cardiac events (group B). Peak velocities during isovolumic contraction (is) and ejection (ez) were interrogated at the mitral or tricuspid annulus (site 1), at the mid parts of the walls (site 3, at the level of papillary muscle), and at the midpoints (site 2) between sites 1 and 3 of interventricular septum (S), lateral wall of LV (L) and of RV (R) in apical 4 chambers view.</p><p><b>RESULTS</b>R1is, R2is, R2ez, R3is, S1is, S1ez, S2ez, L1is, L1ez and L2ez of group A were significantly lower than those in group B (all P < 0.05). Independent of VO(2max), high sensitivity and specificity were shown for R3ez, S1ez, L1ez, L1is, L2is and L3is in predicting cardiac events of DCM patients.</p><p><b>CONCLUSION</b>LV and RV systolic velocities could independently predict cardiac events in DCM patients.</p>