Animals ; Genes, BRCA2 ; Genes, erbB-1 ; Genes, erbB-2 ; Genes, p16 ; Genes, p53 ; Genes, ras ; Genetic Predisposition to Disease ; genetics ; Humans ; Pancreatic Neoplasms ; classification ; genetics ; pathology

Objective To assess the feasibility of a novel 99Tcm labelled polypeptide analogue for interleukin-11 receptor ( IL11R) imaging in a bone metastases model for prostate cancer. Methods A novel circular polypeptide analogue of IL11 ( c( CGRRAGGSC ) ) was indirectly labeled with 99Tcm and the product was named as 99Tcm-DTPA-IL11 RR. The labeling efficiency, radiochemical purity and stability of the product were measured with paper chromatography and high performance liquid chromatography (HPLC). The biodistribution of 99Tcm-DTPA-IL11RR was investigated in 28 ICR normal mice. The organ radioactivity was measured as percentage activity of injection dose per gram of tissue ( %ID/g). The models of bone metastases from prostate cancer were established at the tibias of BALB/c nude mice bearing human prostate cancer PC-3 cells. The tumor bearing ( n= 5 ) and standard closed fracture nude mice models underwent both 99Tcm-DTPA-IL11RR and 99Tcm-methylene diphosphonate (MDP) scintigraphy study. The images were acquired at 0.5, 1,2, 4, 6, 8, 24 h after intravenous injection of the tracers. The competitive inhibition imaging was perfomed in three tumor bearing mice. One-way variance analysis was used. Results The labeling efficiency was 90.7%. The radiochemical purity of 99Tcm-DTPA-IL11RR in normal saline solution was (99.57 ±0.09)%, (99.29 ±0.18)%, (98.95 ±0.78)%, (98.67 ±0.11)%, (96.53 ±0.91)%, (95.20±0.70)%, (88.38 ±0.22)% and (36.17±1.29)% at room temperature after0, 1,2, 3, 4, 6, 8 and 24 h, respectively. The tracer radiochemical purity in the blood of ICR mice remained over 90% at 37 C for 6 h. The labeling compounds were excreted mainly through kidney. The peak uptake of bone ( ( 1.910 ±0.109) %ID/g) and liver ( (0.366 ±0.030) %ID/g) was at 4 h after injection. In the tumor bearing mice, the uptake of spine marrow and large joints of extremities was mild. The highest uptake at tumor region was at 4 h and persistent at 6-8 h after injection. The tumor to non-tumor ratios (T/NT) were 1.17 ±0.17, 2.20 ±0.29, 3.20 ±0.15, 3.67 ±0.23, 13.61±0.85, 9.45 ±0.37 and 3.33 ±0.30 at 0.5,1, 2, 4, 6, 8 and 24 h, respectively (F=621.54, P＜0.05). In the standard closed fracture models,high uptake of 99Tcm-MDP was shown at the fracture site, with no increased 99Tcm-DTPA-IL11RR uptake noted. The tumor uptake was significantly depressed after a pre-injection of the unlabeled polypeptide analogue. Conclusions The synthesis of 99Tcm-DTPA-IL11RR is stable and the labeling efficiency is high. It may be a potential molecular probe in metastatic bone imaging for prostate cancer.

OBJECTIVETo study possible mechanisms of Shangjuxu (ST37) and the large intestine.

METHODSTotally 40 SD rats were selected. The distension of end colon was used as injured afferent stimulus. Activities of locus coeruleus (LC) neurons were recorded by extracellular microelectrode technique. Shangjuxu (ST37) and Hegu (L14) were needled to observe general features of discharge reactions, distention of colon induced discharge reactions of LC, and its effects on distention of colon induced discharge reactions of LC.

RESULTSDistention of colon could induce incrased discharge of LC neurons by 127.33% ± 45.48%. But needling at Shangjuxu (ST37) and Hegu (L14) could inhibit this injured response by 38.24% ± 7.69% and 21.29% ± 13.16% respectively (all P < 0.01).

CONCLUSIONSNeedling at Shangjuxu (ST37) and afferent signals of colon distension converged and interacted with each other. Needling at Shangjuxu (ST37) could significantly inhibit colon distension induced discharge of LC neurons, which might be one of mechanisms for Shangjuxu (ST37) and the large intestine relationship.

Objective To investigate the inhibitory effect of testosterone on oxidized low-density lipoproteins ( ox-LDL)-stimulated phenotypic transition and proliferation of vascular smooth muscle cells ( VSMCs) in vitro, and to explore its possible mechanisms. Methods Rat VSMCs cultured in vitro were divided into control group, ox-LDL group(50μg/mlox-LDL),fetalbovineserum(FBS)group(10% FBS),andtestosteronegroups(5×10-8 or5×10-7 mol/L testosterone plus 50μg/ml ox-LDL) . The effect of testosterone on ox-LDL-induced proliferation of VSMCs was explored by WST-1 assay. The cell cycle distribution was determined using flow cytometry. Western blotting was used todetecttheexpressionsofmitofusin2(Mfn2),phosphorylatedextracellularsignal-regulatedkinases1/2(p-ERK1/2) , proliferating cell nuclear antigen ( PCNA) ,α-smooth muscle actin (α-SMA) ,and osteopontin ( OPN) . Results Compared with control group, the proliferation of VSMCs was promoted by ox-LDL, the number of VSMCs decreased in G0/G1 phase and increased in S phase significantly, the expression levels of Mfn2 and α-SMA were significantly reduced, and the expression levels of p-ERK1/2, PCNA, and OPN were significantly raised in ox-LDL group. Compared with ox-LDL group, the proliferation of VSMCs was inhibited, the number of VSMCs increased in G0/G1 phase and decreased in S phase in two testosterone groups, along with the increased expressions of Mfn2 andα-SMA, and the descended expressions of p-ERK1/2, PCNA, and OPN. Conclusions Testosterone inhibits phenotypic transition and proliferation of VSMCs induced by ox-LDL in vitro, which may be related to the up-regulated expression of Mfn 2 and the suppression of ERK1/2 pathway.

Objective To investigate the direct inhibitory effects of 153Sm- DTPA-c (Cys-Gly-Arg-Arg-Ala-Gly-Gly-Ser-Cys) NH2 ( 153 Sm-DTPA-c (CGRRAGGSC)) on human prostate cancer PC-3 cells. Methods 153Sm-DTPA-c(CGRRAGGSC) was synthesized by the reaction of 153SmCl3 with DTPA-c(CGRRAGGSC) using indirect synthesis method. PC-3 cells in vitro culture were divided into four study groups, groug A ( the control, with PBS only), group B with 1.5 mg/L c ( CGRRAGGSC), group C with 370 kBq 153 SmCl3 and group D with 370 kBq 153Sm-DTPA-c(CGRRAGGSC). PC-3 cell growth was assayed by 3-(4, 5-dimethylthiazol-2-yl ) -2, 5-diphenyltetrazolium bromide (MTT) method. Cell cycle and apoptosis were analyzed by flow cytometry. The expression changes of interleukin 11 (IL11 ) and IL11 receptor (IL1 1 R) in PC-3 cells were examined by Western Blot. One way analysis of variance (ANOVA) and paired-t test were applied for statistic analysis. Results The labeling yield of 153Sm-DTPA-c (CGRRAGGSC) was 85% and the radiochemical purity was 95.8%. The specific activity of 153Sm-DTPA-c(CGRRAGGSC) was 1.32 × 105 MBq/μmol. Significant inhibitory effects on the growth of PC-3 cells were found in both group C and D, with a time-dependent manner. However, no obvious inhibition was found either in group A or in group B. After 48 h,significant differences of sub-G1 peak area were found among groups, (0. 98 ± 0. 18)%, (0. 35 ±0. 10)%, (4.05 ±0.28)% and (13.38 ±0. 89)% for group A, B, C and D, respectively. Furthermore,sexpression of ILl 1R in group D was significantly lower than that in group B and C with absorbance values 0. 339 ~ 0.014, 0.338 ~ 0.019, 0.226 ~ 0. 015 for group B, C and D, respectively. Absorbance values in groups B and C were not significantly different after treatment, compared with those before treatment; however, there was difference between absorbance values after and before treatment in group D ( t = 0. 405,1. 163,135.989,P>0.05 >0.05, <0.05). Conchluion 153Sm-DTPA-c(CGRRAGGSC) can directly in hibit the cell growth and expression of human prostate cancer cells PC-3.

OBJECTIVE To explore a novel pH-sensitive fluorescent probe for in vivo tumor imaging. METHODS Zn5 were obtained in 140℃ after mixed with MeOH, water, Zn(NO3)2 · 6H2O, H4L and trimethylamine. The fluorescence spectra of Zn5 with the same concentration in different pH aqueous solutions were detected. And the stability of Zn5 was investigated by time dependent fluorescence emission spectra of Zn5 in BSA aqueous solution and 5.0% serum solution. Then, the cytotoxicity of Zn5 was detected by MTT assays. To clarify whether a similar fluorescence response occurs in biological organisms, HeLa cells were pretreated with probe Zn5 (0.5 μmol·L- 1) and fluorescence imaging were collected for targeting lysosomes in living cells because of lysosomes' acidic microenvironment. The A375 tumor-bearing mice were used to assess the imaging ability of Zn5 in vivo. Mouse tumor xenografts were established by injection of A375 cells with 2×106 cells per flank. Probe (1 μg·g-1) was administered to mice by injection. Images were obtained using IVIS Spectrum CT Imaging System. RESULTS There is a 11-fold intensity increasing as the pH values changing from 8 to 2. The almost unchanged emission intensities suggest Zn5 is stable in both BSA and serum. Zn5 has negligible cytotoxicity for HeLa, 293T and CHO-K1 cells. Zn5 can selectively display lysosomes in living cells. Both the 2D and 3D images in vivo distinguish the tumor from other tissues with good fluorescence contrast. CONCLUSION The high chemical stability, emission in the Vis/NIR range, pH sensitivity, a pKa located in the tumor pH range, and low toxicity make Zn5 is suitable for application as a pH- sensitive fluorescent probe for bio-imaging.

Background Recent studies have demonstrated that epicardial flow in nonculprit arteries,which has been assumed to be normal,was slowed in the setting of ST-elevation myocardial infarction (STEMI).However,the impact of primary percutaneous coronary intervention (PCI) on blood perfusion in nonculprit arteries in patients with STEMI has not been clarified.The purpose of this study was to investigate the impact of primary PCI on blood perfusion in nonculprit arteries in patients with STEMI and correlated clinical factors.Methods A total of 117 patients with anterior wall STEMI,the culprit artery being the left anterior descending artery (LAD),undergoing primary PCI (the study group) and 100 patients with normal coronary angiography (the control group) were enrolled.To observe the differences of corrected TIMI frame count (cTFC) and myocardial blush grade (MBG) before and after primary PCI in both culprit and nonculprit arteries,the left circumflex coronary artery (LCX),cTFC and MBG in the LAD and LCX were measured in the study group and control group.The study group was divided into three groups; reflow in the culprit artery group (the R group),no reflow in culprit artery group (the NR group),and no reflow in both the culprit artery and nonculprit artery group (the NRB group) according to MBG grade.The level of serum C-reactive protein (CRP),catecholamine,and fibroblast growth factor-21 (FGF21) were assayed.The clinical and angiographic characteristics were also analyzed.Results cTFC (28.1±24.3 vs.20.3±19.3,P ＜0.05) and MBG in the LCX were different in the study group compared to the control group before primary PCI.cTFC (25.2±22.3 vs.28.1±24.3,P ＜0.05) and the MBG level in the LCX were improved after successful primary PCI,but were not recovered to the normal level.Patients with no reflow in the culprit artery had a higher incidence of no-reflow in the nonculprit artery (78％ vs.19％,P ＜0.0001),and the levels of CRP ((3.29±1.31) mg/dl vs.(2.51±1.14) mg/dl vs.(2.93±1.07) mg/dl,P ＜0.05,respectively),catecholamine ((epinephrine (693.48±89.78) pg/ml vs.(398.12±93.28) pg/ml vs.(562.54±96.22) pg/ml,P ＜0.0001,respectively),and norepinephrine ((7012.43±932.47) pg/ml vs.(4012.34±814.16) pg/ml vs.(5549.03±912.65) pg/ml,P ＜0.0001,respectively)) in the NRB group were higher than those in the R group and NR group.The level of FGF21 ((0.299±0.093) ng/ml vs.(0.612±0.071)ng/ml vs.(0.428±0.074) ng/ml,P ＜0.0001 respectively) in the NRB group was lower than that in the R group and NR group.Conclusions The blood perfusion in the nonculprit artery may be impaired in patients with STEMI.Although nonculprit artery perfusion may be improved after successful primary PCI,it is still lower than that in the control group,and may be involved in inflammation and spasms.

Critical Care ; Critical Illness ; Emergencies ; Female ; Humans ; Infant ; Infant, Newborn ; Intensive Care Units, Pediatric ; Male ; Retrospective Studies ; Transportation of Patients

Objective: To investigate the role of NF-?B in signal transduction of hepatocyte apoptosis in liver injury. Methods: A total of 42 Chang-Bai piglets were divided into 7 groups: control group, 1, 2, 4, 8, 12, and 24 hours wound group. The model of intestinal perforations due to abdominal firearm wound was established in wound groups. Hepatic NF-?B activity was measured with immunohistochemical staining and image analysis in all groups. Hepatocyte apoptosis indexes and serum ALT levels were also determined. Results: Levels of hepatic NF-?B activity in wounded groups were significantly elevated compared with control group, and there were two peaks (1 and 8 hours group P

Adolescent ; Blood Vessel Prosthesis Implantation ; Child ; Child, Preschool ; Ductus Arteriosus, Patent ; therapy ; Equipment and Supplies ; Female ; Humans ; Infant ; Male ; Video Recording