The paper aims to explore the studying method for the pharmacokinetics of drugs in target organs, the pharmacokinetic process of tramadol hydrochloride in the extracellular fluid of frontal cortex (FrCx) of mice was investigated. Six male mice (Kunming strain) were anaesthetized (urethane, 1.8 g x kg(-1), ip) and secured on a stereotaxic frame. A microdialysis probe was implanted into the FrCx and perfused with artificial cerebrospinal fluid at a flow rate of 2 microL x min(-1). One hour later, mice were administrated (ip) with tramadol hydrochloride (50 mg x kg(-1)) and dialysates were collected continuously at 12-min intervals (24 microL each) for 6 h. The tramadol concentration in dialysates was determined by HPLC-Ultraviolet detection method, and the concentration-time curve and pharmacokinetic parameters of tramadol were calculated with DAS software. The results showed that the pharmacokinetic process of tramadol in the FrCx extracellular fluid of mice was fitted to a two-compartment open model, and the main pharmacokinetic parameters t1/2alpha, t1/2beta, t(max), C(max) and AUC(0-infinity) were (0.27 +/- 0.05) h, (2.72 +/- 0.24) h, (0.50 +/- 0.10) h, (2 110.37 +/- 291.22) microg x L(-1) and (4 474.51 +/- 441.79) microg x L(-1) x h, respectively. In conclusion, a studying method for pharmacokinetics of drugs in the target organ is established, which is simple and feasible. Tramadol hydrochloride shows a two-compartment model in the extracellular fluid of the mouse FrCx, and the distribution- and elimination half-life are 0.5 h and 2.7 h, respectively.

To guide the reasonable clinical application of modafinil (MOD), pharmacokinetics and pharmacodynamics of MOD in mice and the correlation between them were investigated. Male mice (Kunming strain) were given a single oral dose of MOD (120 mg x kg(-1)). The plasma concentration of MOD was measured by HPLC and the pharmacokinetic parameters were calculated with DAS 3.0 software. For another batch of male Kunming strain mice, their locomotor activities were recorded by an infrared ray passive sensor after a same oral dose of MOD, and the synchronization and correlation between the changes of MOD plasma concentration and the locomotor activity induced by MOD were compared and analyzed. The results showed that the plasma concentration-time curve of MOD was fitted to two-compartment open model with a first order absorption. The main pharmacokinetic parameters t1/2alpha, t1/2beta, t(max), C(max) and AUC(0-inifinity) were 0.42 h, 3.10 h, 1.00 h, 41.34 mg x L(-1) and 142.22 mg x L(-1) x h, respectively. MOD significantly increased locomotor activity and the effect lasted for about 4 h. The changes of MOD plasma concentration and the locomotor activity induced by MOD were synchronous. In conclusion, there is a significant correlation between the effect of MOD and its plasma concentration after administration of 120 mg x kg(-1) in mice.

Objective To compare the result differences of different dynamic nerves transferring to different segments of the radial nerve. Methods From 1997 to 2000, different ways of intercostal nerves or contralataral C 7 transfering to different segments of the radial nerves were carried out in 36 cases with total avulsed brachial plexus injuries that were followed up for average 42.39 months. Four-fold table was selected to statistically calculate the effective rate of muscle strength recovery. Results The total effective rate was 56% (20/36). The effective rate of the functional rehabilitation of elbow extension was 5/8 in the group with neurotization to radial nerve trunk and 4/4 in the group with neurotization to branches innervating the triceps brachii muscle of radial nerve. The highest effective rate up to 75% (9/12) of the functional rehabilitation of wrist and digit extension belonged to the group with contralateral C 7 transferring to the radial nerve segment in the humeral spiral groove where branches innervating the triceps brachii muscle had already diverged. Conclusions The way of neurotization to radial nerve trunk and to branches innervating the triceps brachii muscle of the radial nerve can win good functional rehabilitation of elbow extension. Contralataral C 7 transfering to the radial nerve segment in the humeral spiral groove ranks the best way for function recovery of the wrist extension. Age below 30 years and operation interval less than 12 months are helpful for functional rehabilitation of the radial nerve.

Objective To study the clinical characteristics and diagnosis of the solid-psendopapillary tumor of pancreas (SPT).Methods The clinical data of 40 SPT from January 1996 to January 2008 were retrospectively analyzed. The average age was (32.9 + 13.6 )years. The average clinical course was (8.6±0.1) months.Clinical symptoms usually included distensible pains and secret anguish in abdomen (60.0%).No jaundice appeared in any case.Results The surgical resection was favorable for the treatment of SPT,which had excellent prognosis.No tumor recurrence were found in those following-up patients. Grossly,the cut surface showed areas of solid and papillary tissue,cystic degeneration,hemorrhage,and necrosis.Pathological features included a combination of solid and cystic components with pseudopapillae formation and degenerative regions without glands.Conclusions SPT has its uniquely clinical and pathological characteristics.Its main diagnosed points are helpful for clinical doctors to make timely diagnosis and reduce the rate of misdiagnosis and mistreatment.

Objective:To investigate the effect of heat shock protein B8 (HspB8) downregulation on retinal ganglion cell (RGC) and retinal function in the mice model of optic nerve injury (ONC).Methods:Adeno-Associated Virus (AAV) 2 AAV2-shHspB8-GFP was constructed to knockdown HspB8. 66 adult male C57/BL6 mice were randomly divided into the control group, the ONC group, the AAV2-shHspB8 group, the ONC+AAV2-shHspB8 group, and the ONC+AAV2-GFP group. There were 10, 20, 16, 10 and 10 mice respectively, and both eyes were used as experimental eyes. Western blot was used to evaluate the expression of HspB8 on day 3 and 7 after ONC. By GFP immunofluorescence staining, the efficacy of AAV2-shHspB8-GFP transfer was accessed. Moreover, it was possible to identify functional and RGC survival differences between groups by optomotor response (OMR), dark adapted full-field flash electroretinogram (ff-ERG), oscillatory potentials (OPs), photopic negative response (PhNR) and retinal flat-mount RGC counting 5 days after ONC. Comparisons between two groups were made using Mann-Whitney U test, unpaired t-test, unpaired t-test with Welch’s correction, one-way ANOVA, and Bonferroni t test. Results:Compared with the control group, the expression of HSPB8 protein in the retina of mice in ONC3 group was significantly increased, and the difference was statistically significant ( F=43.63, P<0.01). Compared with the control group, the ONC group showed obviously lower visual acuity ( P<0.01), lower a-wave, b-wave, OPs, PhNR amplitude, longer b-wave latency ( P<0.05), and the survival rates of RGC in ONC3 group, ONC5 group and ONC7 group decreased in a time-dependent manner( F=384.90, P<0.01). Transfection of AAV2 efficiency was highest on 4 weeks after IVT. Besides, there was no significant differences between the control group and the AAV2-shHspB8 group on visual acuity, ff-ERG, OPs, PhNR and RGC survival ( P>0.05). In comparison of the control group, we found that RGC survival of the ONC5+AAV2-shHspB8 group was significantly elevated ( F=10.62, P<0.01). Conclusions:Expression of HspB8 on the retina can be induced by ONC. The investigation of RGC counting, visual acuity, and ff-ERG revealed that optic nerve injury destructed functionality of mice retina and resulted to RGC death ultimately. The Most crucial finding of this research is that HspB8 knockdown had a neuroprotective effect in RGC after ONC.

Objective To investigate the application value of functional magnetic resonance imaging nethods diffusion weighted imagingand dynamic contrast-enhanced magnetic resonance imaging in theT stagingof rectal cancer.Methods Through the retrospectively analysis of DWI and DCE-MRI images of 78 rectal cancer patients confirmed by pathology,the different of routine sequence examination and functional magnetic resonance imaging combined with routine sequence examination in T thestaging diagnosis were contrasted analysis.The correlation of ADC value and quantitative parameters of Ktrans,Kep and Ve values with tumor T staging was analyzed.Results The functional magnetic resonance imaging combined with routine sequence examination in T staging screened 68 cases successfully,and the accuracy rate was 87.2％.preoperative T staging and postoperative pathology of rectal cancerwas better thanroutine sequence examinationin T staging (59 cases,with the accuracy rate 75.6％) (Kappavalue:0.81 vs 0.65,P ＜ 0.05).The ADCvalue andDCE-MRI quantitative parameters values of K and Ve increased with the increase of tumor T staging (P ＜ 0.05).There was no statistically significant difference of Kep values.Conclusions The ADC value and DCE-MRI quantitative parameters (K and Ve values) had certain relevance with Tstaging of rectal cancer.The functional magnetic resonance imaging had a high accuracy in the preoperative T staging of rectal cancer,which proves certain clinical value in judging invasion depth of tumor in the rectal wall.

Objective To improve the diagnosis and management of solid-pseudopapillary tumor (SPT) of the pancreas. MethodsTwenty-two SPT patients were retrospectively reviewed and divided into two groups, misdiagnosed group and those with preoperatively correct diagnosis. ResultsAbout one half (46%) SPT cases were misdiagnosed preoperatively. With time SPT tends to invade its capsule resulting in impossibility of radical resection, and increased medical expenses. ConclusionsAlthough SPT is of low degree malignant, and the prognosis after surgical resection is satisfactory, misdiagnosis and preoperative misdiagnosis and inappropriate management still cost the patients increased expenses and inhospital stay.

Objective To explore the clinical significance and operational methods during extended radical excision for pancreatic cancer combined with portal vein ( PV )/superior mesentery vein ( SMV ) resection,and to investigate the management of iatrogenic arterial injury. Methods Clinical date of 242 patients with pancreatic cancer undergoing extended radical excision were retrospectively analyzed. All cases were divided into three groups, patients with PV/SMV resection were in group A (n = 51 ), patients with iatrogenic arterial injury during operation were in group B(n =5) ,patients without resection of vessels werein group C (n = 186 ). Operating time、volume of intraoperative blood transfusion, time of vascular interruption、the mean hospitalization,postoperative complications and postoperative survival analysis among three groups were compared with each other. Results Operating time in group A、B and C were (442. 85 ± 102. 32 ) min, ( 348. 62 ± 92. 31 ) min and ( 315.00 ± 83.43 ) min respectively, volume of intraoperative blood transfusion were ( 1430. 83 ± 1092. 43 ) ml、( 1420. 22 ± 794. 41 ) ml and ( 928. 19 ±571.57) ml respectively,operating time and volume of intraoperative blood transfusion were of significantly difference(P <0. 05) among the 3 groups,there was no significant difference in the mean hospitalization and postoperative complications. The postoperative median survival period was 18.4 months for patients of pancreatic adenocarcinoma with PV/SMV resection, the postoperative median survival period was 16. 1 months without PV/SMV resection, there was no significant difference between these by postoperative survival analysis. In the 51 cases with vessel resection,7 cases underwent partial resection of the vascular wall,44 cases underwent segmental resection, reconstruction of the portal vein was performed by end-to-end anastomosis in 38 patients, stent graft in 6 cases, the mean length of the PV/SMV resection was (2. 92 ±1.35 ) cm; latrngenic arterial injury occurred during operation in 5 patients ( 1 in hepatic artery, 1 in superior mesenteric artery, 3 in celiac think), the artery was reconstructed by end-to-end anastomosis in 4 cases,repair in 1 case. Conclusions Active and reasonable operation for pancreatic cancer with PV/SMV resection is important for improving the rate of surgical resection and the quality of life. Because of complex topography,iatrogenic vascular injury may happened frequently.

Objective:To investigate the effects of Krüppel-like factor 7 (KLF7) on the survival of retinal ganglion cells (RGCs) and electroretinogram (ERG) after retinal ischemia-reperfusion (RIR) injury in mice.Methods:A total of 126 male C57BL/6J mice were randomly divided into normal group, RIR group, normal-KLF7 group, normal-green fluorescent protein (GFP) group, RIR-KLF7 group and RIR-GFP group. At the age of 8 weeks, mice of normal-KLF7 group and RIR-KLF7 group were intravitreally injected 1ul of 1.0×10 12 vg/ml adeno-associated virus overexpressing KLF7 (AAV2-KLF7-GFP). Mice of normal-GFP group and RIR-GFP group were injected adeno-associated virus of AAV2-GFP with the same titer. At the age of 11 weeks, RIR injury was induced in mice of RIR group, RIR-KLF7 group and RIR-GFP group, and intraocular pressure was measured. Retinal cryosections were used to access the efficacy of virus transfection 4 weeks after AAV2-KLF7-GFP transfer. 7 days after RIR injury, RGCs' survival rate was observed and quantified by immunofluorescent staining. ERG was performed to observe the differences in amplitudes and incubation period of scotopic ERG a-, b-wave, oscillatory potentials (Ops), photopic negative responses (PhNR). Optomotor response was performed to observe the differences of visual acuity. Expression of KLF7 was detected by western blot 4 weeks after AAV2-KLF7-GFP transfer. Results:Compared with normal group, RGCs’ survival rates, amplitudes of ERG a-, b-wave, Ops, PhNR and visual acuity of mice in RIR group were decreased, and the differences were statistically significant ( t=12.860, 7.157, 5.735, 8.953, 4.744, 9.887; P<0.05). With the increase of light intensity, the amplitudes of scotopic ERG a- and b-wave were gradually increased while the incubation period was gradually shortened. Compared with RIR group, RGCs’ survival rates, amplitudes of ERG a-, b-wave, Ops, PhNR and visual acuity of mice in RIR-KLF7 group were increased, and the differences were statistically significant ( t=6.350, 3.253, 3.695, 5.825, 5.325, 4.591; P<0.05). Protein level of KLF7 was up-regulated in normal-KLF7 group than those in normal group, and the difference was statistically significant ( t=4.105, P<0.01). Conclusion:Overexpression of KLF7 can improve RGCs’ survival rates and preserve the electrophysiological function.

Objective To study the application of dynamic contrast-enhanced MRI (DCE-MRI)in preoperative TN staging of rectal cancer. Methods Seventy-two patients with rectal cancer confirmed by surgery and pathology underwent preoperative conventional MRI and DCE-MRI.The consistencies between conventional MRI and pathology,conventional MRI combined with DCE-MRI and pathology in diagnosing the TN staging were analyzed retrospectively.The quantitative parameters of DCE-MRI including Ktrans,Veand Kepwere measured to analyze the correlation with T staging and lymph nodes metastasis.Results The accuracy of conventional MRI and conventional MRI combined with DCE-MRI in diagnosing the T staging were 72.2% and 84.7%,respectively,in diagnosing the N staging were 65.3% and 77.8%, respectively.The DCE-MRI quantitative parameters (Ktransvalue,Vevalue and Kepvalue)were positively related to the T staging and lymph nodes metastasis(P<0.05).Conclusion DCE-MRI can improve the accuracy of the preoperative TN staging of rectal cancer. DCE-MRI quantitative parameters of Ktrans,Ve,Kepvalues can help to determine T staging and lymph node properties of rectal cancer.