Hemostatic mechanism of Jianpi Yiqi Shexue decoction in treatment of immune thrombocytopenia.

OBJECTIVE: To explore the early hemostatic mechanism of Jianpi Yiqi Shexue decoction (, JYSD) in treating immune thrombocytopathy (ITP), based on the functional homeostasis of brain-intestine axis and blood neurotransmitter METHODS: Non-drug treatment cases: Healthy volunteers were selected as normal control group and compared with patients with dysfunctional uterine bleeding, gastrointestinal tumors with bleeding and ITP, to detect the changes of blood 5-hydroxytryptamine (5-HT), ß-endorphin (ß-EP), vasoactive intestinal peptide (VIP) and compare the changes of blood neuro-transmitters in patients with different disease symptoms. Drug treatment cases: According to the randomized controlled multicenter clinical trial, 272 ITP patients were randomly divided into three groups: treatment group (JYSD) combined group (JYSD + Prednisone) control group (Prednisone). The changes of blood neuro-transmitter (5-HT, ß-EP, VIP) before and after treatment were detected on the basis of peripheral blood platelet (PLT) and grade score. RESULTS: Non-drug treatment cases: compared with the normal control group, the 5-HT level was higher, and the VIP and ß-EP levels were both lower in the ITP group (P < 0.001), and the 5-HT, VIP and ß-EP levels in the Gastrointestinal tumors with bleeding group were also lower compared with the normal control group (P < 0.05, 0.001). Drug treatment cases: The PLT grading scores of the combination group and the control group after treatment were lower than that before treatment (P < 0.05, 0.001). The PLT grading score of the 3 groups were compared in pairs after treatment: the combination group was the lowest among the 3 groups, which was better than the treatment group, but no better than the control group (vs the treatment group, P = 0.005, vs the control group, P = 0.709). The statistical results of full analysis set (FAS) and per protocol set (PPS) were consistent. The bleeding symptom scores of the treatment and combination groups began to drop 7 d after treatment, and kept dropping 14 d after treatment until the end of the study (P < 0.05). On the other hand, the control group started to show favorable results 14 d after treatment (P < 0.05). The FAS and PPS analysis results were consistent. In the control group, the 5-HT level was higher and VIP level was lower after treatment, compared with those before treatment (P < 0.05, 0.001). The ß-EP levels were both increased in the treatment and combination group after treatment, compared with those before treatment (P < 0.05). After treatment, the ß-EP levels in the treatment and control groups were significantly lower compared with the combination groups (P < 0.05). After treatment, compared with the control group, the VIP levels in the treatment and combination groups were up-regulated, and the differences were statistically significant by rank sum test (P < 0.01), and by t-test (P = 0.0002, 0.0001). CONCLUSIONS: The prednisone tablet is better than the JYSD in increasing the level of PLT, while prednisone tablet combined with JYSD has more advantages in improving patients' peripheral blood PLT levels. However, in improving the bleeding time of ITP patients, the combination of the two drugs was significantly delayed compared with the single usage, showing the characteristics and advantages of traditional Chinese medicine. JYSD can regulate the neurotransmitter level of ITP patients through the function of the brain-gut axis, mobilize 5-HT in the blood of ITP patients to promote the contraction of blood vessels and smooth muscles, and activate the coagulation mechanism are the early hemostatic mechanisms of JYSD. Up-regulate the levels of ß-EP and balancing VIP levels may be an important part of the immune mechanism of JYSD for regulating ITP patients.

Chemosensitivity of miRNA-17-92 high expression in leukemia animal models and the chemosensitization function of compound Zhebei granules / 白血病·淋巴瘤

Objective@#To observe the effect of miR-17-92 overexpression on the chemosensitivity of leukemia mice and the chemosensitivity of compound Zhebei granules.@*Methods@#The miR-17-92 over-expressed cells and L1210 cells were conventionally infused into each DBA/2N mouse through the vena caudalis at the cellular concentration of 100×104. The mice were divided into 5 groups with a randomized method, including miR-17-92 high expression L1210 cell leukemia mice (miR-17-92) observation group, miRNA-17-92 chemotherapy group, miRNA-17-92 chemotherapy combined with compound Zhebei granules group, L1210 chemotherapy group and normal control group. The chemotherapy groups were given cyclophosphamide by intraperitoneal injection, or chemotherapy combined with compound Zhebei granules group plus compound Zhebei. In the course of the experiment, the routine blood and white blood cell classification were checked every 7 days. The animals were killed on the 15th day or before dying. Peripheral blood routine and white blood cell classification were detected, the proportion of leukemia cells was checked by using bone marrow morphology. Furthermore, it was necessary to weigh the spleen and observe histopathological changes. P-glycoprotein (P-gp) expression was detected by using enzyme-linked immunosorbent assay.@*Results@#The difference between hemoglobin and platelet count on the 15th day after administration was statistically significant in the miRNA-17-92 observation group, miRNA-17-92 chemotherapy group, miRNA-17-92 chemotherapy combined compound Zhebei group, L1210 chemotherapy group, and normal control group (F= 5.76, P= 0.002; F= 16.90, P= 0.002); Compared with the normal control group, peripheral blood leukocyte count in the miRNA-17-92 observation group was decreased (P < 0.05). The proportion of peripheral blood leukemic cells was (37.2±13.1)%, (5.7±1.9)%, (1.3±0.8)%, (0.8±0.3)%, 0, and the proportion of myeloid leukemia cells was (26.9±11.0)%, (6.8±2.0)%, (3.2±1.0)%, (1.7±1.2)%, 0, and the difference was statistically significant (F= 24.38, P= 0.000 0; F= 19.71, P= 0.000 0). The spleen weights were (0.70±0.18), (0.20±0.07), (0.44±0.17), (0.23±0.19), (0.60±0.18) g respectively, and the difference was statistically significant (F= 8.78, P= 0.032). Chemotherapy could reduce leukemia spleen infiltration. P-gp was (33±11), (27±11), (32±11), (20±11), (17±3) ng/ml, and the difference was statistically significant (F= 10.42, P= 0.034). Compound Zhebei granules did not significantly reduce P-gp expression.@*Conclusions@#The overexpression of miRNA-17-92 leads to the decrease of chemotherapy response rate. Compound Zhebei granules combined with chemotherapy could improve the response rate of miR-17-92 high expression L1210 mice.