Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Brain ; drug effects ; pathology ; Disease Models, Animal ; Estrogens ; pharmacology ; Female ; Hypoxia-Ischemia, Brain ; drug therapy ; In Situ Nick-End Labeling ; Male ; Rats ; Rats, Wistar

Aim To study the effect of the total flavonoids of turpinia arguta seen (TFS) on immune function of rats with adjuvant arthritis. Methods Adjuvant arthritis (AA) was induced on d0 by intradermal injection of Complete Freund′s Adjuvant (FCA), containing 10 mg heat-inactive BCG in 1ml paraffin oil. On d 28 after immunization, AA rats were killed by cervical decollation. Immune cells (splenocytes and peritoneal macrophages) were obtained, then cultured in vitro with TFS. Some immune indexes were detected respectively such as the splenocytes proliferation and the productions of IL-1 and IL-2 were measured by the method of cell proliferation, the production of prostaglandin E2 was determined by radioimmunoassay. Results Compared with normal groups, the response of splenocytes to ConA and LPS was lowered, IL-2 syn-thesis was decreased, and IL-1 and PGE_2 released from PM? were elevated. TFS (10~ -8 ~10~ -4 mg?L~ -1 ) not only increased splenocytes proliferation, which induced by ConA and LPS, and IL-2 production of splenocytes, but also reduced the elevated productions of IL-1 and PGE_2 released from peritoned macrophate in AA rats in vitro. Conculsion TFS could adjust abnormal immune function in AA rats.

Objective To study the mechanism of organic anion trans-porting polypeptide1B1 (OATP1B1) and cytochrome P2C9 (CYP2C9 ) genetic polymorphism effect on the metabolism and transport of fluvasta-tin.Methods Build OATP1B1*1a,*5and*15 recombinant plasmid model and CYP2C9*1,*3 recombinant enzyme model to compare up-take and enzymatic kinetic parameters of fluvastatin in different models.Results The fluvastatin intake of OATP1B1*5 gene, OATP1B1*15 gene, OATP1B1*1a gene are ( 3.27 ±0.53 ), ( 6.88 ±2.01 ), (6.32 ±1.23 ) pmol· min-1· mg-1 protein.Compared with OATP1B1*1a, OATP1 B1*5 reduces the transport capacity of fluvastatin ( P <0.05 ) and OATP1B1*15 gene increases (P<0.05).The CLintof CYP2C9*3 and CYP2 C9*1 metabolizing fluvastatin are 0.42 , 1.25 ( P<0.05 ).The activities of CYP2C9*3 are lower than CYP2C9*1.Conclusion The OATP1B1 521 site and the CYP2C9 359 site might be the molecular action site of transport fluvastatin.Therefore , more attention should be payed in clinical applications to prevent damage caused by OATP 1B1 and CYP3A4 genetic polymorphism.

OBJECTIVE: To construct a technological platform of 2-dimensional tumor microvascular architecture phenotype (2D-TAMP) expression. METHODS: Thirty samples of non-small cell lung cancer (NSCLC) were collected after surgery. The corresponding sections of tumor tissue specimens to the slice of CT perfusion imaging were selected. Immunohistochemical staining,Gomori methenamine silver stain, and electron microscope observation were performed to build a technological platform of 2D-TMAP expression by detecting the morphology and the integrity of basement membrane of microvasculature, microvascular density, various microvascular subtype, the degree of the maturity and lumenization of microvasculature, and the characteristics of immunogenetics of microvasculature. RESULTS: The technological platform of 2D-TMAP expression was constructed successfully. There was heterogeneity in 2D-TMAP expression of non-small cell lung cancer. The microvascular of NSCLC had certain characteristics. CONCLUSION 2D-TMAP is a key technology that can be used to observe the overall state of micro-environment in tumor growth.
Capillaries ; ultrastructure ; Carcinoma, Non-Small-Cell Lung ; blood supply ; pathology ; Humans ; Lung Neoplasms ; blood supply ; pathology ; Neovascularization, Pathologic ; pathology ; Phenotype ; Regional Blood Flow ; physiology

OBJECTIVETo investigate the expression of HER2/neu, Ki-67 and TK1 protein in meningiomas in correlation with tumor grades and recurrence.

METHODSTwenty cases of each of the following types of meningiomas were selected for the study, namely: the benign non-recurrent, recurrent benign, atypical and malignant, according to the World Health Organization (WHO) histological classification of nervous system, 2007. Immunohistochemistry study for HER2/neu, Ki-67 and TK1 protein was performed. HER2/neu gene amplification was detected using FISH. Cases with HER2 protein overexpression were studied by immunohistochemistry staining. The results of the biomarker assays were also used to study the correlationship with the tumor grades and tumor recurrency.

RESULTSImmunohistochemistry showed that the positive rates of HER2 expression in non-recurrence benign group, recurrence benign group, atypical group and malignant group were 3 cases (15%), 6 cases (30%), 7 cases (35%), and 10 cases (50%), respectively (P < 0.05). A higher tumor grade was correlated with a higher rate of HER2/neu expression. The Ki-67 and TK1 labeling index (LI) in non-recurrence group were lower than those in the atypical or malignant group (P < 0.05), whereas the atypical group had lower LI than that of the malignant group (P < 0.05). Higher levels of LI of Ki-67 and TK1 were correlated with higher tumor grades and recurrence of the benign meningiomas (P < 0.05). Expression of HER2 was positively correlated with Ki-67 and TK1 (r = 0.445, P < 0.01; r = 0.501, P < 0.01, respectively), and there was a positive correlation between Ki-67 and TK1 (r = 0.450, P < 0.01) as well. HER2/neu gene copy amplification in 7 of 26 cases (26.9%) of HER2 immunopositive meningiomas. The rates of HER2/neu gene amplification were 0 in tumors with 1+ immunopositivity, 4/6 in tumor with 2+ immunopositivity and 3/4 in tumor with 3+ immunopositivity. HER2/neu gene amplification in 3+ and 2+ immunopositive cases had no statistical significance (P > 0.05). Aneuploidy of chromosome 17 existed in 9 of 26 of HER2 immunopositive meningiomas (34.6%). However, the rates of chromosome 17 aneuploidy had no significant difference among tumors with variable HER2/neu imumopositivity (P > 0.05).

CONCLUSIONSHigh levels of HER2 and Ki-67 or TK1 expression correlate with the increase of tumor grades and tumor recurrence. HER2/neu gene amplification is seen in a subset of meningiomas with the protein expression (26.9%). A combination of biomarker study including HER2/neu, Ki-67 and TK1 may be useful in predicting the biological behavior of meningiomas.

Aneuploidy ; Chromosomes, Human, Pair 17 ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen ; metabolism ; Male ; Meningeal Neoplasms ; genetics ; metabolism ; pathology ; Meningioma ; genetics ; metabolism ; pathology ; Middle Aged ; Neoplasm Recurrence, Local ; Receptor, ErbB-2 ; genetics ; metabolism ; Thymidine Kinase ; metabolism

The present study was designed to observe the influence of cerebral ischemia/reperfusion injury on learning and memory in hyperlipidemic rats and estimate the changes of activity of autonomic nervous system. Twenty-three male Wistar rats were randomly divided into three groups, named control group (C group, n=10), hyperlipidemia group (H group, n=6) and hyperlipidemia-ischemia group (HI group, n=7), respectively. The rats in H and HI group were fed a high-fat diet for 2 weeks and the rats in all groups were examined through Morris water maze (MWM) task. The rats in HI group underwent ischemia/reperfusion by 2-vessel occlusion (2-VO) method, and had electrocardiogram (ECG) recording simultaneously. The MWM task and ECG recording were taken again after 7 d of recuperation. The following results were obtained: (1) In the second place navigation performance and probe trial performance, the frequency of memory in quadrant of hidden-platform and memory score decreased significantly in HI group compared to that in C and H groups. (2) The heart rate in HI group decreased slowly after ischemia; the power at high frequency band (HF) reduced gradually, meanwhile the power at middle frequency band (MF) and the ratio of power at MF and HF decreased clearly compared to baseline value. (3) After 7 d of ischemia/reperfusion, the heart rate in HI group was significantly higher than that in H group (P<0.05). While there was no statistical change in the power at MF, the power at HF decreased and the ratio of MF/HF increased significantly (P<0.05). The data demonstrated that ischemia/reperfusion decreased the activity of autonomic nervous system, and the reduction of sympathetic nerve activity was much more than that of vagus nerve activity. The results suggest that the hippocampus neuron injury caused by ischemia induces cognitive disorder and imbalance of vago-sympathetic nerve activity accompanied by vagus nerve suppression.
Animals ; Autonomic Nervous System ; physiopathology ; Brain Ischemia ; etiology ; physiopathology ; Heart Rate ; physiology ; Hippocampus ; physiopathology ; Hyperlipidemias ; complications ; Learning Disorders ; etiology ; physiopathology ; Male ; Memory Disorders ; etiology ; physiopathology ; Random Allocation ; Rats ; Rats, Wistar ; Reperfusion Injury ; pathology ; physiopathology

Physiologically based pharmacokinetic ( PBPK ) models are built using a mathematic framework which is similar to these classic phar-macokinetic ( PK ) models, and are parameterized based on known physiology knowledge, and comprise many compartments corresponding to different organs and tissues in the body, which are connected by flow rates that parallel the circulating blood system.The values of PBPK models are gradually appreciated in the industry of drug development, especially in the field of drug -drug interaction due to their robust ability to predict drugs’ kinetic process in vivo.Then some basic concepts, advantages over classic models and their applications in drug-drug interaction fields asso-ciated with transporters of PBPK models are reviewed in the next context.

Objective To explore the effects of health belief model education on compliance about volume status in peritoneal dialysis patients. Methods 41 peritoneal dialysis patients who were followed-up regularly accepted health belief model education about volume control. Their volume status, compliance and cognition were analyzed. Results After the education, the patients' total fluids cleaning and KT/V decreased markedly, but their volume status had no difference (P＞0.05); Their compliances with dialysis prescription and taking medicine remained good (＞80%), while the compliances in salt and water diet had statistical meaning (P＜ 0.05). And their cognitions in every aspect had obvious improvement (P＜0.05). Conclusions Health belief model education could improve peritoneal dialysis patients' compliance about volume status, thus improving their volume status.

Objective:To investigate the expression of RNF38 in lung cancer,and its correlationship with clinicopathologic feature and prognosis.Methods:Tissue microarray was used to detect the level of RNF38 in 208 lung cancer patients,then its correlationship with clinicopathologic feature and prognosis was analyzed.Results:RNF38 expression was higher in lung cancer tissues compared with the corresponding adjacent normal lung tissues.High level of RNF38 was related significantly to tumor size (P= 0.0002),tumor stage (P= 0.011),lymph node metastasis (P= 0.00004)and histological type (P= 0.030 ).High level of RNF38 indicates low overall survival rate.Single factor analysis showed that RNF38 expression was related to lung cancer patients'prognosis.Conclusions:The high level of RNF38 could be a new marker in predicting the prognosis of lung cancer.

BACKGROUND: Activation of CD40 pathway negatively regulates the therapeutic effect of endothelial progenitor cells (EPCs), while inhibition of this pathway can enhance the biological function of the cells. OBJECTIVE: To compare the therapeutic effects of CD40-silenced EPCs (EPCs shRNA-CD40) and conventional EPCs transplantation in an animal model of pulmonary hypertension, and to explore the interventional effect of astragalosides on EPCs transplantation in the treatment of pulmonary hypertension. METHODS: Ninety SD rats were randomly divided into five groups: normal control group (n=24), model group (n=24), lentivirus transfection group (n=18), conventional transplantation group (n=18) and astragaloside group (n=6). Except the normal control group, the remaining four groups were given monocrotaline to induce pulmonary hypertension. Rats in the lentivirus transfection and conventional transplantation groups were given intravenous injection of Lv-shRNA-CD40-transfected EPCs and conventional EPCs respectively at 7, 14, 21 days after modeling (n=6 at each time point). Rats in the astragaloside group were given daily intraperitoneal injection of 80 mg/(kg?d) astragaloside within 1-21 days after modeling, and then Lv-shRNA-CD40-transfected EPCs were intravenously injected at 21 days after modeling. Hemodynamics, plasma endothelin-1 level and right ventricular hypertrophy index were detected at 28 days after modeling. RESULTS AND CONCLUSION: (1) After modeling, right ventricular pressure, mean pulmonary arterial pressure and right ventricular hypertrophy index were all increased compared with the normal control group (P < 0.05), while these indices were then decreased significantly after EPCs transplantation (P < 0.05). With the increasing of transplantation time, there was an increasing trend in the right ventricular pressure, mean pulmonary arterial pressure and right ventricular hypertrophy index in the two EPCs transplantation groups, but this trend was not remarkable in the lentivirus transfection group. (2) After modeling, the level of endothelin-1 was increased significantly compared with the normal control group (P < 0.05), and then decreased after EPCs transplantation (P < 0.05). The level of endothelin-1 in the lentivirus transfection group was significantly lower than that in the conventional transplantation group at the same time point (P < 0.05). (3) A significant improvement in hemodynamics, plasma endothelin-1 level and right ventricular hypertrophy index was observed in the astragaloside group as compared with the lentivirus transfection group (P < 0.05). Given the above findings, CD40-silenced EPCs transplantation is more effective and durable than the conventional transplantation in the treatment of pulmonary hypertension, and moreover, astragaloside can enhance the therapeutic effect.