Objective To investigate the rule of the cerebral tissues aquaporin-4(AQP-4) expression in acute and chronic hepatic failure mice.To study the molecular biologic mechanism of the diffusion weighted imaging(DWI).Methods Sixty five male Sprague-Dawley rats were divided into 3 groups randomly,including acute(n=25),chronic hepatic failure(n=25)and control group(n=15). Thioacetamide(TAA)intraperitoneal injection produces the acute and chronic hepatic failure models.All rats in groups were examined with MR DWI.We Observed the distribution of abnormal signal on DWI.The DWI single values of top and lateral cortex of parietal lobe,peripheral region of lateral ventricle in the highest hyperintensity section of brain were measured.Blood ammonia values were examined.The pathologic and immuno-histochemistry and RT-PCR examination for brain specimen were performed.All date were analyzed with statistical methods.Results The mean values of blood ammonia were significantly different (P0.05).Conclusions Increase of the blood ammonia was the main cause for the brain energy metabolic abnormality and AQP-4 mRNA and protein expression.The hyperammonemia was the key factor in the occurrence and development of the hepatic brain edema.The abnormal findings in DWI signal could reflect the range and degree of the brain edema and AQP-4 protein expression.

OBJECTIVETo observe the intervention effect of Leihong Granule (LG) in in-stent restenosis (ISR) after endovascular therapy for lower extremity arterial occlusive diseases (LEAOD).

METHODSRecruited 80 LEAOD patients who successfully underwent endovascular therapy (balloon dilation and stent implantation) were randomly assigned to two groups, the control group and the LG group, 40 in each group. Patients in the control group received basic treatment, while those in the LG group additionally took LG for 3 months. Plasma levels of IL-10, IL-18, CRP, and the intima-media thickness (IMT) of lower extremity artery were observed in the two groups between and after treatment. The rate of stent patency, ABI, intermittent claudication, rest pain, and the incidence of amputation the two groups were recorded and observed in the two groups.

RESULTSIn the control group, serum levels of IL-10, IL-18, CRP, and IMT were significantly higher one month after surgery than before surgery (P < 0.05). There was no significant difference in serum levels of IL-10, IL-18, CRP, or IMT between the two groups before surgery (P > 0.05). These indices were obviously lower in the LG group than in the control group after surgery (P < 0.05). Compared with the control group, the incidence rates of intermittent claudication and the rest pain at 6 months and 12 months after surgery significantly decreased (P < 0.05). The stent patency rate at 6 months and 12 months after surgery, and ABI were significantly higher than those of the control group (P < 0.05). There was no statistical difference in the amputation rate between the two groups (P > 0.05).

CONCLUSIONLG might effectively improve ischemic symptoms of affected limbs possibly through lowering the ISR rate after endovascular therapy for LEAOD through preventing immunosuppressive actions.

Aged ; Aged, 80 and over ; Arterial Occlusive Diseases ; therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Graft Occlusion, Vascular ; therapy ; Humans ; Interleukin-10 ; blood ; Interleukin-18 ; blood ; Lower Extremity ; blood supply ; Male ; Middle Aged ; Phytotherapy ; Stents ; Treatment Outcome

Objective To study the risk factors related with progressive hemorrhagic injury (PHI)after severe head injury for a view to early diagnosis and treatment for this disease and providing a basis for effective prevention. Methods In a retrospective study of 262 patients with severe brain injury in considering the clinical data of the PHI, the occurrence is variable, and age, gender, bleeding site, type of bleeding, dilated pupils starus, level of systolic blood pressure on admission, time of CT for the first time,GOS scores, injured mechanism, interval between first and second time CT, application of high-dose mannitol, platelet (PLT) count, prothrombin time (PT), activated partial prothrombin time (APTT) were considered as independent variables. Results The incidence rate of having PHI was 47.7% (125/262);single-factor analysis revealed that, as compared with those in patients with non-PHI, 7 factors in patients with PHI were significantly different, namely, age, type of hemorrhage, interval between injury and first-time CT, GCS scores, PLT count, PT and APTT. Multivariate logistic regression analysis of the results showed that interval between injury and first-time CT, GCS scores, PLT count were the risk factors of having PHI, and their OR values were 3.5448, 3.2975 and 2.2361, respectively. Conclusion For patients with severe brain injury, the sooner the first time CT examination is performed, the lower the GCS scores are and the lower the PLT count is, the higher risk of having PHI is. Thus, dynamic CT formal review is suggested to improve the early diagnosis and treatment of PHI.

Objective To assess the value of real-time intraoperative neuronavigation integrated with ultrasound in the resection of deep-seated brain tumor. Methods Thirty patients with deep-seated brain tumor were treated with microneurosurgery guided with real-time ultrasound integrated with the Brain Lab IGSonic navigation. During the ultrasound based operation, the degree of brain shift and the tumor border was timely observed, and then the tumor was resected totally. Results Guiding with navigation integrated ultrasound, we noticed the brain shift with various degrees happening in 30 patients,and the border of tumor was exposed and the tumor was resected totally without serious complications.Conclusions Intraoperative ultrasound integrated with navigation is a reliable guidance which can accurately re-localize the border of deep-seated brain tumor even when the tumor is shifting, timely delineate the reformatted images from ultrasound and totally resectcd the tumor, thus decrease the surgical time and increase the safety of surgical procedure.

The purpose of this study is to investigate the reversal effect and its mechanism of arsenic trioxide (As2O3) on multidrug resistance of gastric carcinoma cells. The concentration of vincristine (VCR) increased gradually to induce the drug resistance of gastric carcinoma cell SGC7901. MTT assay was used to determine the lethal effect of anticarcinogens on tumor cells and Western blotting assay was applied to determine the expression of P-glucoprotein (P-gp) and glutathione S-transferase (GST-s) in tumor cells. As a result, the resistance of SGC7901/VCR cells to VCR, fluorouracil and epirubicin was 16.56, 2.69 and 13.05 times, respectively, more than that of SGC7901 cells. After 24 h precondition with As2O3, RI of vincristine, fluorouracil and epirubicin decreased significantly (P < 0.05). Expression of P-gp and GST-s in resting SGC7901/VCR cells was significantly higher than that in carcinogen-sensitive SGC7901 cells. As2O3 decreased the expression of P-gp and GST-s in SGC7901/VCR cells significantly, while it showed no significant effect on carcinogen-sensitive SGC7901 cells. The result suggested that As2O3 could partly reverse drug resistance of SGC7901/VCR cells by probably the mechanism of decreasing the expression of P-gp and GST-s.
ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Adenocarcinoma ; metabolism ; pathology ; Antineoplastic Agents ; pharmacology ; Arsenicals ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Epirubicin ; pharmacology ; Fluorouracil ; pharmacology ; Glutathione Transferase ; metabolism ; Humans ; Oxides ; pharmacology ; Stomach Neoplasms ; metabolism ; pathology ; Vincristine ; pharmacology

AIMTo establish an analytical method for determination of guanfu base A (GFA) concentration in plasma and to study its pharmacokinetic profile in dogs.

METHODSSix dogs were given a 7.56 mg.kg-1 dose intravenously. Blood samples were collected at various time-points after drug administration. Analytical method based on liquid chromatography-mass spectrometry (LC-MS) was established to determine the plasma concentration of GFA. Pharmacokinetic evaluation was carried out using the 3P87 program.

RESULTSThe calibration curves were linear over the concentration range from 0.42 microgram.mL-1 to 21.2 micrograms.mL-1 (gamma = 0.9994). The intra-day and inter-day precisions were generally good (< 15%) at low, medium and high concentrations. The overall recovery of the analytes was more than 80%. Six dogs were given an i.v. dose of 7.56 mg.kg-1 of GFA hydrochloride, an open three compartment model best described the concentration-time profiles for GFA. The half-lives for the rapid and slow distribution phase and terminal elimination phase (T1/2 pi, T1/2 alpha and T1/2 beta) were 0.07 h, 1.5 h, and 13.5 h, respectively. The total area under the plasma concentration-time curve (AUC), the volume of the central compartment (Vc), and plasma clearance (CLs) were 61.43 micrograms.h.mL-1, 0.37 L.kg-1 and 0.14 L.kg-1.h-1, respectively.

CONCLUSIONThe analytical method was shown to be sensitive, specific, rapid and reproducible, and was suitable for pharmacokinetic studies of GFA.

Aconitum ; chemistry ; Alkaloids ; blood ; isolation & purification ; pharmacokinetics ; Animals ; Area Under Curve ; Chromatography, Liquid ; methods ; Dogs ; Female ; Gas Chromatography-Mass Spectrometry ; methods ; Heterocyclic Compounds, 4 or More Rings ; Male ; Metabolic Clearance Rate ; Plants, Medicinal ; chemistry

OBJECTIVETo investigate the role of PERK/eIF2alpha signaling pathway in hepatocyte apoptosis of alcoholic liver injury rats.

METHODSRat models with ethanol-induced liver injury were successfully developed by gastric gavage with ethanol-corn oil mixtures for 12 weeks. At different time points (4, 6, 10, 12 week), liver pathology was dynamically observed. The hepatocyte apoptosis was quantitatively analyzed by Annexin V-FITC/PI double-labeled flow cytometry, the serum total homocysteine (tHCY) level was detected by ELISA and the expressions of eIF2a, p-eIF2a, GRP78/Bip, GRP94, caspase-3 and caspase-12 in liver were examined using Real-time PCR and Western blot.

RESULTSTypical acute liver injury and chronic liver injury were observed at week 4 and week 12 respectively. The hepatocyte apoptosis rates in 6-week model rats significantly increased compared with normal rats (P value less than 0.05), and the degree of hepatocyte apoptosis continued to increase with the modeling time, and the percentages of early and total apoptosis reached 26% and 29% at week 12. From week 6 to week 12, the serum tHCY levels in model rats were obviously higher than in normal rats (P value less than 0.01). Since week 4, eIF2a protein phosphorylation in model rat livers remarkably elevated compared with that in normal rat livers (P value less than 0.01), and at week 12 the peIF2a protein expression in model rat livers increased by 2.81-fold. Since week 4 the expressions of GRP78/Bip, GRP94, caspase-12 and caspase-3 mRNA and protein in model rat livers showed a significant increase as compared to normal rat livers, and at week 12, these gene and protein levels increased 4.70, 12.95, 3.83, 4.05 fold and 3.93, 6.93, 9.88, 3.31 fold, respectively (P value less than 0.01).

CONCLUSIONActivation of PERK/eIF2a signaling pathway contributes to the occurrence and development of hepatocyte apoptosis in alcoholic liver injury rats and it might be as a potential target for therapeutic applications in alcoholic liver diseases.

Animals ; Apoptosis ; Eukaryotic Initiation Factor-2 ; metabolism ; Hepatocytes ; cytology ; pathology ; Liver Diseases, Alcoholic ; metabolism ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; eIF-2 Kinase ; metabolism

Translational medicine is a systemic project because it is patient and clinical problems oriented, aiming at research results application, and involves multidisciplinary cooperation. Studies on molecular events in the precancerous stage, early stage and metastasis of colorectal cancer (CRC) are the CRC hot research topics currently. Investigations on the earliest molecular events can help to find out the markers which may improve the effect of CRC screening and predict CRC liver metastasis and prognosis. Based on the concept of micro environment, molecular targeted drugs to interfere with metastasis and invasion and new concepts of surgical resection margin and neoadjuvant therapy will gain recognition from clinicians.
Colorectal Neoplasms ; Humans ; Translational Medical Research

Objective To analyse the preliminary clinical results of intensity modulated radiation therapy (IMRT) for 122 untreated nasopharyngeal carcinoma (NPC)pafients.Methods 122 NPC pa- tients received IMRT alone from Feb.2001 to Jun.2004,with 31 females and 91 males,and a median age of 45 years(range 25-66).According to the Fuzhou Stage Classification,there were StageⅠ11 patients, StageⅡ34,StageⅢ62,and StageⅣa 15.IMRT was carried out using an inverse planning system (COR- VUS 5.0,Peacock plan) developed by the NOMOS Corp.The treatment was given with the Multi-leaf Inten- sity Modulating Collimator (MIMIC) using a slice-by-slice arc rotation approach.The prescription dose was 68 Gy/30f to the nasopharynx gross tumor volume (GTV_(nx)),60-66 Gy/30f to positive neck lymph nodes (GTV_(nd)),60 Gy/30f to the first clinical target volume (CTV_1) and 54 Gy/30f to the second clinical target volume (CTV_2).Kaplan-Meier method was used to calculate the overall survival rate (OS),distant metas- tasis-free survival rates (DMFS),and local-regional control rates from the last date of therapy.Log-rank test was used to detect the difference between groups.Results The median follow-up time was 20 months ( range 6 to46 months).The 1-,2-,and 3-year OS was 95.2%,91.4%,85.1%,DMFS was 91.9%, 88.6%,85.6%,and the local-regional control rates was 96.5%,93.2%,93.2%,respectively.Statistics of the local control rate was insignificant either for advanced T(T3+T4) stage or early T(T1+T2) stage diseases(P=0.148).The 2-year regional control rate was insignificant either for patients with N(+) or N (-),but the 2-year DMFS was significant both for patients with N(+) and N(-)lesions(P=0.004).For 17 patients who failed,there were two with residual disease and one with recurrence at the primary site (17.6%),three patients in the neck (17.6%),twelve patients (70.6%) in distant metastases.Conclu- sions Intensity modulated radiation therapy does provide excellent local-regional control for untreated NPC, especially in patients with advanced T stage or N(+) lesion.Distant metastasis is the main cause of failure. N (+) is significantly correlated with distant metastasis.

BACKGROUNDExternal stents have been used to reduce intimal hyperplasia of vein grafts. The aim of the present study was to define the size of an external stent appropriate for a particular graft by comparing vein grafts with different sizes of external stents.

METHODSA series of paired trials was performed to compare femoral vein grafts with different sizes of external stents, where 30 modeled canines were equally divided into three groups: 6-mm external stent vs non-stent control, 4-mm vs 6-mm external stent, and 4-mm vs 8-mm external stent. At day 3 after operation, color Doppler flow imaging (CDFI) was done to observe blood flow in the lumen. Four weeks later, CDFI was re-checked and the veins were harvested, stained and measured.

RESULTSAll grafts were patent without formation of thrombosis. External stents significantly reduced intimal thickness of the vein grafts with a 6-mm external stent compared with the vein grafts without external stents (P < 0.05). The vein grafts with the 4-mm external stent had similar intimal, medial and adventitial thicknesses compared with those with the 6-mm external stent and the 8-mm external stent.

CONCLUSIONSExternal stents can reduce intimal hyperplasia of vein grafts. Stents of different diameters exert the similar effect on prevention of intimal hyperplasia.

Animals ; Aspirin ; therapeutic use ; Dogs ; Femoral Vein ; transplantation ; Hyperplasia ; Stents ; Tunica Intima ; pathology ; Ultrasonography, Doppler, Color