OBJECTIVE To map a comprehensive metabolic pathway of herbacetin in rats, specifically, to elucidate the biotransformation of herbacetin in vivo and to simultaneously monitor the pharmacokinetic process of both parent drug and its major metabolites. METHODS liquid chromatography/ion trap mass spectrometry (LC/MSn) and ultra-liquid chromatography coupled with mass spectrometry (UPLC/MS) were combined in the current study for qualitative and quantitative determinations of herbacetin and its metabolites in bile, urine and feces after both oral and intravenous administration of herbacetin to rats. Enzyme kinetic studies on the intestinal and hepatic metabolism of herbacetin were further conducted to elucidate metabolic profiles of herbacetin in rat tissues and organs. Additionally, plasma concentration profiles of herbacetin and its metabolites in rats were obtained to characterize the overall pharmacokinetic behavior of herbacetin. RESULTS It was found that herbacetin was excreted primarily from rat urine in the form of glucuronide-conjugations. Subsequent in vitro enzyme kinetic studies and in vivo pharmacokinetic investigations suggested an extensive hepatic metabolism of herbacetin and the high exposure of herbacetin- glucuronides in systemic circulation. The clearance, half- life and bioavailability of herbacetin in rats were determined as (16.4±1.92)mL·kg-1·min-1, (11.9±2.7)min, and 1.32%, respectively. On basis of these findings, a comprehensive metabolic pathway of herbacetin in rats was composed. In addition, a physiology based pharmacokinetic (PBPK) model was successfully developed with the aid of the GastroPlus to simulate the pharmacokinetic process of herbacetin in rats. Application of the PBPK modeling can provide a useful starting point to understand and extrapolate pharmacokinetic parameters among different species, populations, and disease states. CONCLUSION After oral administration, herbacetin was subjected to colonic degradation and extensive first pass metabolism, with glucuronidation as its dominating in vivo metabolic pathway.

OBJECTIVE To investigate the effect of hypoxia on the pharmacokinetic process of salidrosidein rats and to explore its underlying mechanisms. METHODS The Caco-2 cell monolayerwas exposed to 1% oxygen (O2) concentration for 24 h to build the hypoxiccell model. The transportation mode of salidroside was investigated with the aid of this hypoxia model by detecting the apparent permeability coefficient(Papp). Healthy Sprague Dawley (SD) rats were exposed to 9% O2 for 72 h for the construction of hypoxic rat model. Liver sample was subsequently collected from the hypoxic rats with an aim to identify enzymes responsible for salidroside metabolism. The expression levels of sali?droside-transporting and salidroside-metabolizing enzymes, including Sodium-dependent glucose cotrans?porters (SGLT1), β-glucosidase (GBA3)and sulfotransferase (SULT2A1), were thereafter detected by RT-PCR and Western blot. The metabolic activity of GBA3 and SULT2A1 was monitored by rat liver microsome incubation.In addition, the renal function of rats under hypoxia was assessed by detecting concentrations of blood urea nitrogen and creatinine. RESULTS The AUC and t1/2 values of salidroside in hypoxic rats were more than doubled, while the in vivo clearance was significantly reduced. Mechanistic study demonstrated that the PappA- B/PappB- A eualsto 10.3, indicating the potential active transport of salidrosile. The expression of SGLT1 and GBA3 was significantly decreased, which indicated a reduced metabolism of salidroside under hypoxia. Moreover, rat under hypoxia was found to suffer from renal dysfunction, with an abnormal value of blood urea nitrogen. CONCLUSION Due to the reduced metabolism and the abnormal renal function under hypoxia, the systemic exposure of salidroside in rats was signifi?cantly enhanced.

Objective To evaluate the value of stereotactic core needle biopsy(SCNB)in diagnosis of breast lesions.Methods Forty-seven cases were punctured with computer-assisted stereotactic system, spring-loaded biopsy guns and 16 G core needles.The record of each item was collected,including clinical manifestations,descriptions of the mammographic characteristics(such as calcification,mass and architectural distortion),the pathology of the SCNB and the surgical pathology or mammographic follow-up data.Then the results of SCNB were analyzed based on the comparison of SCNB pathology and the surgical pathology.The reason that SCNB failed and misdioagnosed was inferred from the relationship of SCNB accuracy and the X-ray characteristics.Results Forty-four cases were punctured successfully,3 cases failed.Thirty-one patients were operated soon after biopsy.The results of 27 SCNB cases agreed well with the final pathology but the other 4 did not.Conclusions SCNB as an accurate,time-saving and cost- effective method,is also minimally invasive and hardly changes the architecture of the breast.SCNB can diagnose breast lesions in advance,reduces the number of surgical biopsy,and is promising in clinical application.

Objectives: To evaluate the clinical significance of nuclear matrix protein 22 (NMP 22) in the detection of bladder transitional cell carcinoma (BTCC) and compare with voided urine cytology(VUC). Methods: A total of 69 cases with voided urine samples for NMP 22 and VUC test were included in this study. Thirty of them were BTCC patients(BTCC group) and twenty nine suffered from other urological diseases (nonbladder cancer group, NBC group). Ten were healthy volunteers (control group). Results: The NMP 22 values for BTCC group (67.3 U/ml) were significantly higher than that of NBC group(7.4 U/ml) and control group (4.3 U/ml)( P 0.05). NMP 22 was more sensitive than VUC in low grade BTCC(Ⅰ,Ⅱ)(62.50% vs 12.50%,P 0.05). Conclusions:Urinary NMP 22 is a useful marker for the early diagnosis of BTCC. It is more sensitive than VUC in low stage and grade BTCC.

Objective To observe the effect of reperfusion therapy on the prognosis of acute myocardial infarction (AMI) complicated by eardiogenic shock(CS)in reperfusion era.Methods 89 cases of AMI with CS were included with 57 male and 32 female.50 cases received conservative therapy and 39 cases reperfusion therapy.28 of the 39 cases had suecessflll reperfusion and 11 eases failed.18 patients had intra-aortic balloon pump (IABP) within 1 hour of CS,they constituted an early group;35 patients treated with IABP 1 hour after CS were of a late group.A group of 36 cases were not treated with IABP (no IABP group).Results The mortality of the early group with IABP Was significantly lower than that of the late and no IABP group(33.3% vs.74.2% vs.86.1%,P＜0.01).The mortality of the group with sucessful reperfusion was significantly lower than that of unsuccessful reperfusion and conservative no IABP group (42.8% vs.81.8% vs.84.0%,P＜0.01).logistic regression analysis showed that successful reperfusion therapy (OR 4.232,95% CI 1.407～12.730,P=0.01) and THE TIME of using IABP(OR 0.22.95% CI 0.063～0.764,P=0.017)were independent risk factors for death.Conclusion Early successful reperfusion and early institution of IABP were the most important therapeutic measures for reducing mortaliIv of AMI complicated by CS.

Objective To study the CT features of peripheral lung cancer with thin-walled cavity, and to improve the understanding and diagnostic accuracy of this type of lung cancer. Methods Thirty-one patients (male:18, female:13, average age(56 ± 12)years old) with surgically proven peripheral lung cancer with thin-walled cavity were studied retrospectively. There were 28 cases of adenocarcinoma, 2 cases of squamous cell carcinoma and 1 case of sarcomatoid carcinoma. All patients had MSCT examination, and the CT features of the solid lesion and thin-walled cavity of the lung cancer were analyzed. The relationship between solid lesion and thin-walled cavity location, cavity wall thickness and uniformity, wall nodules, vascularstructures close to the outer wall, septum or air-fluid level inside the cavity, and dynamic changes of the lesions were all evaluated. Results (1) Solid lesion:mostly located in both upper and middle lobes of the lung in 21cases (67.7%). Lobulation, speculation and vessel convergence sign were observed in 27 cases (87.1%), 21 cases(67.7% )and 16 cases(51.6%) respectively. Twenty cases showed as ground glass nodule (GGN) (64.5%), with pure GGN in 11 cases(35.5%). (2) Cavitary lesion: The average diameter was (2.7 ± 1.3) cm, the cavity located in the periphery of the solid lesions in 26 cases (83.9%),and in 20 cases (64.5%) located in the lateral or superior and inferior lateral aspect of the solid lesion;The cavity wall was uniform in17 cases (54.8%) and the wall thickness<2 mm were seen in 16 cases (51.6%), 2-3 mm were observed in 10 cases (32.3%);Wall nodules were seen in five cases (16.1%);Blood vessels adjacent to outer wall were found in 12 cases (38.7%);There was no air-fluid level in the cavity in all the cases;But septum with uneven thickness or small vessels were seen in the cavity in 27 cases (87.1%). Conclusions The majority of peripheral lung cancer with thin-walled cavity was adenocarcinoma, characteristic CT features of thin-walled cavitary lesions may be helpful in the diagnosis of this type of lung cancer.

Objective To investigated the effect of the risk factors for stroke on the development of leptomeningeal colateral circulation in patients with middle cerebral artery occlusion. Methods Patients with acute ischemic stroke confirmed as middle cerebral artery occlusion by imaging were extracted from the Nanjing Stroke Registry Program between June 2006 and December 2011. The baseline clinical data were colected. Leptomeningeal colateral circulation was assessed by angiography. Results A total of 137 patients were enroled, including 100 males and 37 females; mean age 55. 26 ± 11. 71 years. The colateral circulation of 65 patients (47. 4% ) was good. Univariate analysis showed that the ages (52. 3 ± 13. 2 years vs. 57. 9 ± 9. 5 years; t = 2. 866, P = 0. 005) and the proportion of hypertension (52. 3% vs. 70. 8% ; χ2 = 4. 978, P =0. 026) in the good colateral circulation group were significantly lower than those in the poor colateral circulation group. Multivariate logistic regression analysis showed that age was an independent risk factor for affecting the leptomeningeal colateral circulation in patients with acute middle cerebral artery occlusion (odds ratio, 0. 965, 95% confidence interval 0. 934-0. 997, P = 0. 034). Conclusions Age is an independent risk factor for affecting the leptomeningeal colateral circulation in patients with middle cerebral artery occlusion.

Objective To investigate the possible formation mechanism and imaging features of the hyperintense vessel sign (HVS) on fluid attenuated inversion recovery (FLAIR) in patients with ischemic stroke or transient ischemic attack (TIA).Methods The baseline data of the patients with middle cerebral artery (MCA) ischemic stroke or TIA with digital subtraction angiography (DSA) showing the lesions of MCA M1 segment in clinical practice were retrospectively retrieved from Nanjing Stroke Registry Program from January 2010 to July 2011.FLAIR was used to observe HVS,and DSA was used to evaluate the degree of vascular stenosis and cerebral collateral circulation.Results A total of 101 patients were enrolled,76 (75.2％) were males,and their mean age was 53.94 ± 13.47 years; 90 patients (89.1％) with ischemic stroke and 11 patients (10.9％) with TIA; 55 patients (54.5％) were HVS negative and 46 (45.5％) were HVS positive.Among the patients whose MCA stenosis ＜50％,50％-70％,70％-90％ and ≥90％,the positive rates were 0％ (0/8),25.0％ (3/12),17.6％ (3/17),and 62.5％ (40/64),respectively.There were significant differences (Z=-4.479,P＜ 0.001).The leptomeningeal collateral circulation of the HVS positive group was significantly more than that of the HVS negative group (Z =-6.196,P ＜ 0.001).Multivariate logistic regression analysis showed that the degree of MCA stenosis was an independent risk factor for influencing the formation of HVS (odds ratio 3.943,95％ confidence interval 2.03-7.659; P ＜0.001).Conclusions The formed intracranial leptomeningeal colhteral circulation after severe intracranial vascular stenosis or occlusion is a major pathophysiological basis of HVS formation on FLAIR sequences in patients with ischemic stroke or TIA.

Objective To detect the expression of GHR in colorectal cancer cell lines and determine whether recombinant human growth hormone can promote the proliferation of colorectal cancer cells in vitro.Methods GHR distribution was assessed by flow cytometry and immunofluorescence method in 9 colorectal cancer cell lines.The effect of recombinant human growth factor on colorectal cancer cell line proliferation was assessed by MTT method.Results Different GHR expression was determinated in 9 colorectal caner cell lines.GHR was highly expressed in HCT-8 while GHR expression could hardly be detected in LoVo.r-hGH could promote GHR(+) HCT-8 cell proliferation at 50 ng/ml and 100 ng/ml (P ＜0.05).But this effect was not dose dependent.When the neutralizing antibody was used to block GHR activity,this r-hGH dependent proliferation effect was eliminated.r-hGH could not promote GHR (-) LoVo cell proliferation (P ＞0.05).Conclusion The results demonstrates that r-hGH could promote GHR (+) tumor cell proliferation and this effect is mediated by GHR.The use of r-hGH on the colorectal cancer patients should be cautious.

AIM: The purpose of this study is to investigate the mechanisms related to oxidized low-density lipoprotein(ox-LDL) and dendritic cells(DCs) in the process of atherosclerosis.METHODS: Human DCs were prepared from human CD14~+ peripheral blood monocytes using rhGM-CSF((100 ?g/L)) and rhIL-4(40 ?g/L).Cells were incubated with(100 mg/L) native or oxidized LDL for 72 h.The formation of foam cells was investigated by electron microscopy and oil red O staining.Phenotypic and immune functional assays were used with FACS,FITC-dextran phagocytosis,allogeneic mixed T lymphocytes reaction and secretion of Th1/Th2(IL-12/IL-2) cytokines were also conduced.RESULTS: DCs treated with ox-LDL,but not native LDL were induced into foam cells after cultured for 72 h.Compared with native LDL,ox-LDL-treated DCs were less potent in FITC-dextran phagocytosis.ox-LDL promoted allogeneic T cells proliferation.Moreover,ox-LDL upregulated CD80(72.4? 9.6 vs 89.5?10.1,P