AIM:To establish a new rat model of depression by the antagonistic relationship of antagonizing pairs of neurotransmitters in the brain.METHODS:Dopamine D1 receptor antagonist SCH23390 was injected into the hippocampus of the rats by microinjection at low, medium and high doses (1, 2 and 4 g/L) to establish a depression model.After modeling, the sucrose consumption, open-field and novelty suppressed feeding tests were used to evaluate the behaviors of the rats, and screen out the best modeling drug dose.The model of depressive rats was induced using the best modeling drug dose and the model rats were observed for 2 weeks.The stability of the model was evaluated by behavioral tests, and the contents of IL-1β and TNF-α in cerebrospinal fluid (CSF) were measured by ELISA to evaluate the safety of the model.The levels of the antagonizing pairs of neurotransmitters in the cerebral cortex and hippocampus were analyzed by the method of high-performance liquid chromatography-mass spectrometry (HPLC-MS), so as to evaluate the pathological characteristics of neurotransmitter imbalance in the brain of the model rats.RESULTS:After modeling, the rat weight, sucrose preference rate, and horizontal motion and vertical motion scores of open-field test were significantly decreased in eACh dose model group, and feeding latent periods of novelty suppressed feeding test were significantly increased, indicating a typical depressive behavior.The rats with the medium dose (2 g/L) of SCH23390 had the most significant depressive behavior.At 2 weeks after modeling, compared with the normal control group, the weight, sucrose preference rate, and horizontal motion and vertical motion scores in medium dose group were significantly decreased (P<0.01), while the feeding inhibition time was significantly increased (P<0.05).No significant difference in the content of IL-1β and TNF-α in the CSF of normal control group, blank control group and medium dose group was observed, indicating that the model did not cause obvious inflammatory injury, and the modeling method was safe.Compared with blank control group, the contents of 5-HT, NE and Glu in the left hippocampus of rats in medium dose group were significantly increased (P<0.01), and the content of DA and ACh showed decreasing trends.The contents of 5-HT, NE and Glu in the right hippocampus of the rats were significantly increased (P<0.05), and the contents of DA and ACh showed decreasing trends.The content of Glu in cerebral cortex was significantly increased (P<0.05), the contents of 5-HT and NE showed increasing trends, and the contents of DA and ACh showed decreasing trends, indicating that the model was basically consistent with the pathological features of neurotransmitter imbalance in the brain of depression.CONCLUSION:This method can successfully replicate the rat model of depression, which has the characteristics of typical and persistent symptoms, fast modeling, and safe and easy operation.Using the dosage of 2 g/L is more suitable.

AIM: To investigate the effect of c-Myc inhibitor 10058-F4 on human chronic myeloid leukemia ( CML) K562 cells and imatinib-resistant K562/G cells.METHODS: The protein expression of c-Myc was detected by Western blotting .Cell proliferation was evaluated by MTT assay and colony formation assay .PI staining was used to deter-mine the cell cycle distribution .Annexin V-PI staining was applied for apoptosis detection .RESULTS:Imatinib-resistant K562/G cells displayed lower sensitivity to imatinib than K 562 cells with high expression of c-Myc.Treatment with specific c-Myc inhibitor 10058-F4 inhibited the cell proliferation in a dose-and time-dependent manner , and K562/G displayed more sensitivity to 10058-F4 than K562 cells.10058-F4 also induced cell cycle arrest in G 0/G1 phase and induced apoptot-ic cell death in the 2 cells.Importantly, 10058-F4 suppressed the colony formation ability in K 562 and K562/G cells. CONCLUSION:c-Myc is a novel target to overcome imatinib-induced drug resistance , and c-Myc inhibitor provides a new approach in CML therapy .

Objective To analyze the risk factors of liver metastasis from gastric cancer. Methods The clinical data of 225 patients with liver metastasis from gastric cancer who had been admitted to our hospital from January 1996 to December 2001 were retrospectively analyzed. Synchronous liver metastasis was observed in 123 patients and metachronous liver metastasis in 102 patients. The risk factors of liver metastasis from gastric cancer were evaluated. Results The gender of patients, location and size of gastric cancer foci, differentiation and invasion depth of gastric cancer, Lanren classification, lymph node metastasis and lymph node metastasis in region Ⅷ, vascular invasion, extrahepatic metastasis, ascites and peritoneal metastasis were the significant factors associated with liver metastasis from gastric cancer (X2 = 43.560-263. 907, P<0.05). All the factors except the size of gastric cancer foci, extrahepatic metastasis and ascites were found to be the significant factors associated with different types of liver metastasis from gastric cancer (X2 = 6.673-26. 555, P < 0.05 ). Logistic regression analysis demonstrated that the gender of patients, lymph node metastasis and peritoneal metastasis were the factors that determined the types of liver metastasis from gastric cancer. Conclusion The gender of patients, lymph node metastasis and peritoneal metastasis are the important factors to evaluate the occurrence of different types of liver metastasis from gastric cancer.

Objective To explore the occurance and risk factors of recurrence and metastasis of gastric cancer after gastrectomy.Methods From January 2001 to December 2004, the clinic pathological data of 141 patients with recurrence and metastasis after radical gastrectomy in Tianjin Medical University Cancer Institute and Hospital were analyzed retrospectively.The possible clinic pathological factors which may affect tumor recurrence were analyzed.Results After the surgery, the 1, 2, 3 and 5-year cumulative recurrence rates were 58.2%(82/141) 、80.1%(113/141)、89.4%(126/141) 、97.9 % (138/141)respectively.The results of multivariate analysis indicated that the tumor size,invasive depth, lymph node metastasis were independent factors which affected recurrence and metastasis after radical gastrectomy (P = 0.017, 0.003, 0.000).Invasive depth, lymph node metastasis and tumor differentiation degree were independent factors which affected early recurrence and metastasis after radical gastrectomy (P=0.042, 0.000, 0.039).Conclusions The tumor size,invasive depth, lymph node metastasis are the independent risk factors to predict the recurrence and metastasis after radical gastrectomy.Most of the recurrences and metastasis is found within 2 years after radical gastrectomy.Invasive depth, lymph node metastasis and tumor differentiation degree are the independent factors to predict early recurrence after radical gastrectomy.

This article was aimed to study the different clinical characteristics using drug pair of Cassia twig and white peony root with the contents ratio of 1:1 and 1:2. Based on the different clinical treatment of drug pair of Cas-sia twig and white peony root, different compositional ingredients in ratio of 1:1 and 1:2 were illuminated by HPLC/MS method. The drug pair of Cassia twig and white peony roots in ratio of 1:1 and 1:2 and single herbs were ex-tracted for HPLC/MS analysis. A protocol was followed, including acetonitrile - 0.1% acetic acid with gradient elution, positive mode, 350℃ capillary temperature and 300℃ vaporization temperature. The results showed that Procyanidol B2 and 2-Hydroxy cinnamal dehyde can be extracted from single Cassia twig, but 2-Hydroxy cinna-mal dehyde cannot be detected in drug pair. It showed the contents of Procyanidol B2 in 1:1 ratio was more than 1:2 ratio. Simultaneously, Palbinone, paeoniflorin sulfonate, 1,2,3,6-Tetra-O-galloyl-β-D-glucose, Paeoniflorin, Pae-oniflorin isomers, Benzoylpaeo-niflorin, and Benzoyl Paeoniflorin isomers can also be dissolved in white peony root. In addition, the contents of 1,2,3,6-Tetra-O-galloyl-β-D-glucose, Paeoniflorin, Benzoylpaeo-niflorin, and Benzoyl Paeoniflorin isomers in 1:1 were more than 1:2. The contents of Palbinone, paeoniflorin sulfonate and Paeoniflorin isomers in 1:2 were more than 1:1. It was concluded that Procyanidol B2, 1,2,3,6-Tetra-O-galloyl-β-D-glucose, Paeoniflorin, Benzoylpaeo-niflorin and Benzoyl Paeoniflorin isomers in 1:1 were more than 1:2. The contents of Pal-binone, Paeoniflorin sulfonate and Paeoniflorin isomers in 1:2 were more than 1:1. It provided a scientific basis for traditional Chinese medicine treatment using rational drug pair.

Objective To explore a clean and efficient new method for extraction of Diosgenin. Methods Yield of the total saponins was evaluated to determine the optimal enzymolysis temperature,pH,solid to liquid ratio,dosage of enzyme and enzymolysis time.Using diosgenin yield as an index,solid to liquid ratio,concentration of sulfuric acid and hydrolysis time were optimized in the saponins hydrolysis process via orthogonal experiment. Results The best conditions for the enzyme pretreatment were as follows:the temperature for enzymolysis was 70℃,pH 5.5,solid to liquid ratio was 1:4,dosage of enzyme was 8 mL?kg-1,and extraction time was 24 h.The best conditions of total saponins hydrolysis were as follows:the solid to liquid ratio was 1:4,concentration of sulfuric acid was 2.0 mol?L-1 ,and hydrolysis time was 5 h. Conclusion The new method is environmental friendly and highly efficient,and expected to be applied in industrial production.

Dioscin chemical compositions are the main effective components in clinical commonly used Chinese medicines such as Diaoxinxuekang capsules and Xinnaoshutong capsules etc , which show distinct curative effect on cardiovascular and cerebrovascular diseases.Meanwhile, they are the important raw materials for the synthesis of steroid hormone drugs .The studies on the extraction technology exhibit important significance in the exploration of pharmacological activities of the components , which also are the external requirements for the growing demand of steroid hormone drugs market .In this paper , the relatively mature extraction methods re-searched in recent years were summarized ,and the advantages and disadvantages of the different processes were discussed in order to provide reference for the further studies and application .

Objective To investigate the effects of baicalin on serum progesterone and related hormones in female normal and cerebral ischemia rats; To explore whether baicalin plays a role in cerebral protection of neurological functions by regulating progesterone levels.Methods With vaginal smear method, the adult estrus female SD rats were selected and divided into normal group, baicalin normal group, and molding groups. The left side of the middle cerebral artery of rats in the molding groups was blocked to establish the permanent middle cerebral artery occlusion (pMCAO). After modeling, the rats were randomly divided into model group, baicalin treatment group, progesterone treatment group and progesterone inhibitor group. The baicalin normal group and baicalin treatment group were given intraperitoneal injection of baicalin solution; the normal group and model group were given normal saline of the same quantity; progesterone treatment group was given intramuscular injection of progesterone; progesterone inhibitor group was given intraperitoneal injection of baicalin solution and intragastric administration of mifepristone solution.The neurological function deficit scores were evaluated and rat forelimb holding power was detected by Grip Strength Meter respectively at different time points. Serum was taken from the rats and the progesterone and related hormones levels in the serum of every group were measured by ELISA. Results Compared with normal group, neurological functions of rats in molding groups were damaged, and neural functional behavior scores of different time points were the most strongly increased (P<0.001), and rat forelimb holding power was the most strongly reduced (P<0.001). 5 days after treating, baicalin showed the trend of improvement of neurological functions (P>0.05) and more significant improvement of the forelimb holding power (P<0.01); 10 days after modeling, baicalin treatment group significantly increased neural functional behavior scorce (P<0.001) and the most significantly improved the forelimb holding power (P<0.001). Compared with baicalin treatment group, the progesterone inhibitor group had a significant inhibitory effect on neural functional recovery (P<0.05) 10 days after modeling, and the group also had a significant inhibitory effect on the recovery of holding power (P<0.05) 5 days and 10 days after treating. At the same time, compared with the model group, progesterone level in baicalin treatment group increased significantly (P<0.05), and FSH and LH decreased (P>0.05).Conclusion After applying mifepristone to block progesterone, baicalin neurologic protection is significantly inhibited. The results demonstrated that baicalin may play a role in cerebral protection via up-regulating serum progesterone level.

BACKGROUND: Microglia play an important role in immune surveillance in their quiescent state, but the role of the activated microglia is under discussion. OBJECTIVE: To analyze the mechanism of activated microglia in acute cerebral infarction. METHODS: Totally 96 male Kunming mice were selected and randomly divided into four groups, including transplantation, placebo, blank control and sham operation groups. Permanent occlusion of the middle cerebral artery was performed using suture method in the mice of the transplantation, placebo and blank control groups, followed by injection of microglia suspension via subclavian vein, medium containing the same volume of microglia, and nothing, respectively, at 12 hours after modeling. In the meanwhile, the same amount of microglia suspension was injected into the mice of the sham operation group. The Zea-longa scale and brain-derived neurotrophic factor expression at 12, 24 and 72 hours after modeling, the volume of cerebral infarction and the number of nerve cells positive for microtubule-associated protein-2 at 72 hours after modeling were detected. RESULTS AND CONCLUSION: The Zea-longa scale score was 0 point in the sham operation group, which was significantly lower than that in the other three groups at each time point after modeling (P < 0.01). The Zea-longa scores in the transplantation group were significantly lower than those in the placebo and blank control groups at 24 and 72 hours after transplantation (P < 0.01). The positive expression rate of brain-derived neurotrophic factor in the transplantation group was significantly higher than that in the other three groups after transplantation (P < 0.01). The sham group showed no infarction, while the size of cerebral infarction in the transplantation group was significantly lower than that in the placebo and blank control groups (P < 0.01), and the microtubule-associated protein-2 positive rate was significantly higher than that in the placebo and blank control groups (P < 0.01). These results manifest that the activated microglia can improve the survival rate of nerve cells, promote the recovery of cerebral nerve function and reduce the size of cerebral infarction.

Objective To investigate the productive effects of baicalin on the male rats with ischemic brain injury and its effects on serum progesterone level in rats; To explore the possible mechanism of baicalin in brain protection. Methods Adult SD male rats were used to create a permanent left middle cerebral artery occlusion model. The rats were evenly divided into model group, baicalin group, inhibitor group, and sham-operation group (without inserted into the intraluminal thread) according to the neurological function scores. At different time points after modeling, the neurological function scores and the grip strength of double foreleg were measured, and the reduction rate of grip strength was calculated. Serum progesterone and adrenocorticotrophic hormone (ACTH) were detected by ELISA. Results Compared with the sham-operation group, the neurological function of rats in the model group was impaired, the grip strength of double foreleg was significantly reduced. 7 days after treatment, compared with the model group, the neurological function score of baicalin group was lowered, grip strength of double foreleg was recovered, reduction rate of grip strength was reduced (P<0.05); compared with the baicalin group, protective effects of baicalin on neurological function was lowered in inhibitor group (P<0.05). 7 days after treatment, compared with the model group, the serum progesterone level in baicalin group was significantly higher (P<0.01), and ACTH level showed an increasing trend; compared with the baicalin group, serum progesterone and ACTH levels in the inhibitor group decreased (P<0.05). Conclusion The protective effects of baicalin on the male rats with ischemic brain injury may be related to the regulation of progesterone.