Exploration of Mechanism of Guben Qingyuan Prescription Combined with Androgen Deprivation Therapy Against Castration-resistant Prostate Cancer from AR/AR-V7 Signaling Pathway / 中国实验方剂学杂志

Objective:To explore the efficacy and mechanism of Guben Qingyuan prescription combined with androgen deprivation therapy （ADT） in the treatment of castration-resistant prostate cancer （CRPC）. Method:A CRPC-bearing mouse model was established. When the tumor volume reached about 100 mm³， 50 CRPC-bearing BALB/c nude mice were randomly divided into the model group， ADT group， and ADT+low-， medium-， high-dose Guben Qingyuan prescription groups， with 10 mice in each group. After grouping， it was ensured that there was no statistically significant difference in tumor volume between groups. The mice in the model group was treated with the same amount of normal saline （10 mL·kg^-1） by gavage， twice a day， while those in the other groups were provided with bicalutamide （5 mg·kg^-1） for intragastric administration， once a day， and then with goserelin （0.36 mg·kg^-1） for intraperitoneal injection on the 10th day. On the basis of ADT， the ones in the ADT+Guben Qingyuan prescription groups further received Guben Qingyuan prescription at the low （2.5 g·kg^-1）， medium （25 g·kg^-1）， and high doses （50 g·kg^-1） by gavage， twice a day. After 25 days of continuous administration， the tumor tissue was harvested for recording the tumor growth and calculating the tumor inhibition rate. The mRNA and protein expression levels of androgen receptor （AR）， androgen receptor splice variant-7 （AR-V7）， and prostate-specific antigen （PSA） were detected by real-time polymerase chain reaction （Real-time PCR） and Western blot assay. Result:The tumor inhibition rates of the ADT+low-， medium-， and high-dose Guben Qingyuan prescription groups were 27.95%， 46.71%， and 44.46%， respectively， and the inhibition rates in the ADT+medium- and high-dose Guben Qingyuan prescription groups were significantly increased as compared with that in the ADT group （<italic>P</italic><0.05）. As revealed by comparison with the ADT group， Guben Qingyuan prescription at the medium and high doses significantly down-regulated the mRNA and protein expression levels of AR， AR-V7， and PSA （<italic>P</italic><0.05）. Conclusion:Guben Qingyuan prescription combined with ADT is efficient in controlling the tumor growth in CRPC-bearing mice， which is related to the regulation of AR/AR-V7 signaling pathway.

Genomewide DNA Methylation Responses in Patients with β-Thalassemia Treated with Yisui Shengxue Granules () / 中国结合医学杂志

OBJECTIVE@#To examine the clinical effects of Yisui Shengxue Granules () in the treatment of β-thalassemia and explore its mechanism on DNA methylation levels.@*METHODS@#A randomized placebo-controlled double-blinded trial was conducted. Forty patients with β-thalassemia were recruited and distributed randomly by envelope method into an experimental group and a control group, 20 patients in each group. The patients were given Yisui Shengxue Granules in the experimental group and placebo in the control group (12 g/bag three times a day) during a 3-month intervention. Before and after 1, 2, and 3 months of treatment, peripheral intravenous blood was sampled, and blood parameters such as hemoglobin (Hb), red blood cells (RBCs), reticulocytes (Ret), and fetal hemoglobin (HbF) were analyzed. Mononuclear cells from 5 patients, who showed an obvious treatment effect, were isolated by density gradient centrifugation. DNA methylation was analyzed using an Affymetrix USA GeneChip Human Promoter 1.0 Array and Input-promoter 1.0.@*RESULTS@#Compared with pre-treatment, there was an obvious increase in Hb and RBCs counts after 1, 2, and 3 months in the experiment group (P<0.01 or P<0.05). Meanwhile, HbF increased from the 2nd to the 3rd month (P<0.05). In the control group, Hb and RBCs showed no obvioas change. After 3-month treatment, DNA methylation results from 5 patients revealed that there were 24 hypomethylated genes and 3,685 hypermethylated genes compared with pre-treatment. Genes of insulin-like growth factor 1 receptor (IGF1R) and Janus kinase 3 (JAK3) revealed the most relations with other genes (degree: 21) and genes of 1-phosphatidylinositol-4, 5-bisphosphate phosphodiesterase gamma 2 (PLCG2) and mitogen-activated protein kinase 10 (MAPK10) showed a stronger intermediary role (betweenness centrality=0.04).@*CONCLUSIONS@#JAK3 and MAPK10 are two key genes in bone marrow and the lymphatic system, and JAK3 is likely to be related to hematopoietic cytokines in the process of early hematopoiesis. (Registration No. NCT01549080).

Development of miniature negative pressure aspirator / 医疗卫生装备

Objective To develop a miniature negative pressure aspirator with easy operation,stable negative pressure,low weight,small volume and high portability.Methods A double-faced printed circuit board with a size of 6 cm×4 cm×1 cm was manufactured with the functions of regulating the current and DC/AC conversion.DC vacuum pump and Panasonic li-ion battery pack were used to generate the desired pressure between-0.017 and-0.060 MPa,and mechanically-driven deformation vacuum gauge was involved in manufacturing the aspirator.Two sizes (150 and 200 ml) of drainage bottles were made of medical silica gel.Results The aspirator facilitated negative-pressure therapy when the patient was walking or discharged,which decreased the hospital cost and stay.Conclusion The aspirator gains advantages in stable negative pressure,low power consumption,easy operation and high safety,and thus is worthy promoting clinically.

Effects of Kaixin Jieyu Decoction () on behavior, monoamine neurotransmitter levels, and serotonin receptor subtype expression in the brain of a rat depression model / 中国结合医学杂志

<p><b>OBJECTIVE</b>To determine the mechanisms underlying the anti-depressant effects of Kaixin Jieyu Decoction (, KJD) by investigating the effects of KJD on behavior, monoamine neurotransmitter levels, and serotonin (5-HT) receptor subtype expression in the brain in a rat model of depression.</p><p><b>METHODS</b>The rat depression model was established using chronic unpredictable mild stress (CUMS). Forty-eight Sprague Dawley rats were randomly divided into control, depression model (CUMS), CUMS+KJD (7.7 g/kg(-1)·d(-1) of crude drug), and CUMS+fluoxetine (2.4 mg/kg(-1)·d(-1)) groups (n=12 in each group), and the treatments lasted for 21 days. We regularly evaluated body weight, sucrose consumption, and horizontal and vertical activity scores in open-field tests. The content of the monoamine neurotransmitters 5-HT, norepinephrine (NE), and dopamine (DA) and the DA metabolite homovanillic acid in the cerebral cortex, and 5-HT1A and 5-HT2A receptor mRNA in the cerebral cortex and the hippocampus, were determined respectively by high-performance liquid chromatography-coularray electrochemical detector and real-time polymerase chain reaction.</p><p><b>RESULTS</b>Compared with the control group, CUMS rats showed a variety of depression-like behavioral changes, including a significant reduction in body weight, sucrose consumption, and horizontal and vertical activity scores in open-field tests (P<0.05 or P<0.01), and a significant decrease in 5-HT and NE levels and 5-HT2A receptor mRNA expression. In contrast, they showed a significant increase in 5-HT1A receptor mRNA expression in the cerebral cortex. In the hippocampus, 5-HT1A receptor mRNA expression was lower whereas 5-HT2A receptor mRNA expression was higher than in the control group (P<0.05 or P<0.01). Treatment with KJD or fluoxetine partially attenuated these changes (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>KJD could normalize the levels of 5-HT and NE and adjust the balance of 5-HT1A and 5-HT2A receptor expression in rat cerebrum, and this may be one of mechanisms of antidepressant effects of KJD.</p>

Effect of Yisui Shengxue Granule () on the oxidative damage of erythrocytes from patients with hemoglobin H disease / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Yisui Shengxue Granule (, YSSXG), a complex Chinese medicine, on the oxidative damage of erythrocytes from patients with hemoglobin H (HbH) disease.</p><p><b>METHODS</b>Twenty-two patients with HbH disease and 22 healthy volunteers were observed. YSSXG was given to patients with HbH disease for 3 months. Before and after the 3-month treatment, blood parameters [hemoglobin (Hb), red blood cells (RBCs), and reticulocyte percent (Ret)] were examined; inclusion bodies in erythrocytes were observed by transmission electron microscopy (TEM); activities of antioxidant defense enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (Cat)] and erythrocyte membrane malondialdehyde (MDA) concentrations were determined.</p><p><b>RESULTS</b>In patients with HbH disease, measured values of RBC and Hb obtained from the first to the third months after treatment with YSSXG were significantly higher than before treatment (P<0.01). Measured values of Ret from the second to the third months after treatment were significantly lower than before treatment (P<0.05 and P<0.01, respectively). Prior to treatment with YSSXG, TEM images of RBCs showed the presence of numerous inclusion bodies. After treatment with YSSXG, the amount and volume of inclusion bodies decreased. Treatment with YSSXG also led to a significant increase in SOD activity (P<0.01), a decrease in Cat activity (P<0.01), and no significant differences in GSHPx activity (P>0.05) or MDA concentration (P>0.05). However, compared with the healthy counterparts, SOD, GSH-Px, and Cat activities presented at high levels (P<0.01) both before and after treatment.</p><p><b>CONCLUSIONS</b>YSSXG could improve the degree of hemolysis and anemia in patients with HbH disease. The mechanism may be related to its antioxidative effects, which could elevate the activity of total SOD in erythrocytes and efficiently inhibit the oxidative precipitation of β-globin chains.</p>

Study on acting mechanism of extracts from ginseng, notoginseng and chuanxiong for delaying the aging of endothelial cells induced by angiotensin II / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effects of extracts from ginseng, notoginseng and chuanxiong (Ext) on the angiotensin II induced aging of human umbilical endothelial cells (HUVECs) in vitro.</p><p><b>METHODS</b>Cultured HUVECs were divided into 5 groups, the blank control group (A), the model group (B), and the three intervening groups (C, D and E). Except those in Group A, all cells were induced into aging model cells by Ang II in a final concentration of 10(-6) mol/L, and to the three intervening groups, corresponding treatments with low dose Ext (C), high dose Ext (D) and valsartan (E) were accessed. Changes of aging in HUVECs were observed by SA-beta-gal staining; cell cycle was analyzed by flow cytometry; contents of reactive oxygen species (ROS) in cells was measured by laser confocal microscopy; levels of nitric oxide (NO) and anti-superoxide anion in culture medium were examined by nitrate reductase method; and the protein expression of NAD (P) H oxidase p47phox, as well as the angiotensin type 1 and 2 receptor (AT1 R, AT2R) were detected by Western blot.</p><p><b>RESULTS</b>Compared with Group A, in Group B, the positive beta-gal stained HUVECs increased and stagnated at G0-G1 phase, with the fluorescence intensity of ROS evidently enhanced; in the culture medium content of NO and anti-superoxide anion were lowered, and protein expression of p47phox and AT1 R up-regulated. While these aging figures were improved in Group C and D. After intervention with high or low dose of Ext, beta-gal stained HUVECs decreased showing less cells in G0-G1 phase and more cells in G2-M phase, the fluorescence intensity of ROS reduced, contents of NO and anti-superoxide anion increased, and the protein expression of p47phox and AT1 R down-regulated.</p><p><b>CONCLUSION</b>Ext could delay the aging of HUVECs induced by angiotensin II, it is possibly by way of down-regulating the expression of NAD (P) H oxidase subunit-p47phox through AT1 R, and further reducing the superoxide anion production.</p>