Anti-tumor mechanism of sesquiterpenoids from Cryptoporus volvatus based on molecular docking / 南方医科大学学报

OBJECTIVE@#To identify the target genes mediating anti-tumor effect of sesquiterpenoids from Cryptoporus volvatus and explore the possible mechanism using molecular docking and molecular dynamics simulation.@*METHODS@#Based on the chemical structure of sesquiterpenes from C. volvatus, we explored the online reverse target finding websites PharmMapper, SEA, Target Hunter and related literature for preliminary prediction of possible anti-tumor targets. Discovery Studio 4.0 (Libdock function) and Maestro 12.3 were used to connect sesquiterpenes with the possible targets, and the potential targets were selected according to the scores. The interaction between the sesquiterpenes and the targets were analyzed using 2D interaction diagram, and the influence of different sesquiterpene skeletons on their activity was inferred based on their activity measurements in experiment. Kinetic simulation was performed for front-end protein sequence (1UNQ) of the Akt (protein kinase B) and for the complex formed by 1UNQ and compound 4 (which had the best cytotoxic activity in vitro) in its optimal conformation, and the root mean square deviation (RMSD) value and root mean square float (RMSF) value of the complex and 1UNQ were measured to evaluate the stability of the binding of compound 4 to the target.@*RESULTS@#The sesquiterpenes showed optimal binding with 1UNQ. Analysis of 2D interaction diagram suggested that the hydrogen bonding and electrostatic force were the most important forces mediating the interaction between the sesquiterpenes and 1UNQ. Analysis of the optimal 3D conformation showed that for different sesquiterpenes, a slight change of the molecular framework produced a steric hindrance effect and caused changes in their bioactivity. Kinetic simulation showed that the complex formed by compound 4 and1UNQ had a lower RMSD than the target pure protein sequence, indicating that compound 4 could stably bind to 1UNQ. The anti-tumor effect of the sesquiterpenoids from C. volvatus was associated with their ability to cause Lys-144 acetylation, which blocks Akt binding to the downstream PIP3 and thus affects the proliferation of tumor cells.@*CONCLUSION@#1UNQ is the target of sesquiterpenoids from C. volvatus, which affects the proliferation of tumor cells by acetylating Lys-14.

Measurement of commonly-used echocardiography indexes and determination of reference values in pregnant women with normal pregnancy / 中国实用妇科与产科杂志

OBJECTIVE: To compare the echocardiography parameters during different pregnancy trimesters and to determine the reference range of echocardiography for pregnant women.METHODS: Normal pregnant women were recruited from Renji Hospital,Shanghai Jiao Tong University School of Medicine from February 2017 to December 2017.Women were randomly assigned into 4 groups,cardiac ultrasonography was performed in any one of the three trimesters or 42 days postpartum,and the reference ranges of indicators were determined in each group.Non-pregnant women of childbearing age were recruited as controls.Make a comparison of the measurement values of echocardiography at different trimesters of pregnancy.RESULTS: A total of 733 normal pregnant and non-pregnant women were enrolled,and reference values of echocardiography indexes were determined.The reference range of echocardiograph parameters for pregnant women was established for the first time.Compared with non-pregnant women,there were significant differences in echocardiography parameters among these groups. With the increase of gestational age,the radial lines of left and right atria and ventricles enlarged;the aortic root diameter and pulmonary artery diameter increased,and left and right heart systolic function declined. Most of the above changes reached a peak in the third trimester and did not return to the nonpregnancy level at 42 days postpartum. The diastolic function did not change significantly throughout pregnancy or 42 days postpartum.CONCLUSION: The current normal reference range of echocardiography is not fully applicable to pregnant women,so it is of great importance to establish a normal reference range of echocardiography for pregnant women.

Qualitative Analysis of Diagnostic Value of 24-h Proteinuria for Preeclampsia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Preeclampsia (PE) is a serious idiopathic disease posing a threat to both mothers and fetuses' lives during pregnancy, whose main diagnostic criteria include hypertension with proteinuria. However, American College of Obstetricians and Gynecologists (ACOG) updated the diagnostic criteria for PE and reduced the diagnostic value of proteinuria for patients with PE. Qualitative analysis of the diagnostic value of 24-h proteinuria for patients with PE in China was conducted to evaluate the diagnostic criteria value in the latest ACOG guideline.</p><p><b>METHODS</b>Complete clinical data of 65 patients with hypertensive disorder in pregnancy (HDP) were collected. All patients were delivered to and hospitalized in Renji Hospital. Adverse outcome was defined in case of the emergence of any serious complication for a mother or the fetus. A retrospective study was conducted according to ACOG guideline, to analyze the relationship between each diagnostic criteria of ACOG guideline and maternal and perinatal outcomes. Spearman correlation test was used to detect the association between each diagnostic criterion, its corresponding value, and the adverse pregnancy outcome. Logistic regression was performed to verify the result of Spearman correlation test.</p><p><b>RESULTS</b>Of 65 HDP patients, the percentage of adverse pregnancy outcome was 63.1%. Adverse pregnancy outcomes constitute diversification. There were 55 cases with 24-h proteinuria value ≥0.3 g, of which the adverse outcome rate was 74.5%. While adverse pregnancy outcomes did not appear in the rest 10 HDP patients with proteinuria <0.3 g/24 h. The statistic difference was significant (P = 0.000). However, no significant difference was found in other criteria groups (impaired liver function: P = 0.417; renal insufficiency: P = 0.194; thrombocytopenia: P = 0.079; and cerebral or visual symptoms: P = 0.296). The correlation coefficient between 24-h proteinuria ≥0.3 g and adverse pregnancy outcomes was 0.557 (P < 0.005). Impaired liver function (P = 0.180), renal insufficiency (P = 0.077) and cerebral or visual symptoms (P = 0.118) were not related to adverse outcomes. The 24-h proteinuria value (HDP: r = 0.685; PE: r = 0.521), liver enzyme value (HDP: r = 0.519; PE: r = 0.501), and creatinine value (HDP: r = 0.511; PE: r = 0.398) were associated with adverse pregnancy outcomes both in PE and HDP, and the corresponding logistic regression equation can be produced.</p><p><b>CONCLUSIONS</b>The 24-h proteinuria value is still an important diagnostic criterion for PE, and deletion of 24-h proteinuria value from diagnostic criteria for severe PE was not recommended. The diagnostic criteria in ACOG guideline need to be verified in Chinese women.</p>

Effect of extract of ginkgo bilboa leaf on early diabetic nephropathy / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of extract of Ginkgo bilboa leaf (EGB) on renal lesions of early diabetic nephropathy (DN).</p><p><b>METHODS</b>Sixty-eight patients with early DN were randomly divided into two groups, the control group (34 patients) and the treated group (34 patients). Patients in both groups received conventional therapy, while additional 9.6 mg EGB was orally taken by patients in the treated group, three times per day. The therapeutic course for both groups was three months. Indexes such as urinary microalbumin (mALB), alpha1-microglobulin (alpha1-MG), immunoglobulin (IgG), transferrin (TF), retinal binding protein (RBP) and N-acety-beta-D-glucosaminidase (NAG) before and after treatment between the two groups were compared respectively.</p><p><b>RESULTS</b>Compared with before treatment, mALB, alpha1-MG, IgG, TF, RBP and NAG obviously decreased with significant difference in the treated group after treatment (P < 0.05). However, no significant decrease in the above-mentioned indexes in the control group (P > 0.05).</p><p><b>CONCLUSION</b>EGB has the protective action on early DN.</p>