Multilayer stents, a new progress in the endovascular treatment of aneurysms / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To review the recent progress of multilayer stents in treating arterial aneurysms and to draw an initial conclusion about its paradigm.</p><p><b>DATA SOURCES</b>PubMed database and ELSEVIER database were searched with the keywords "cardiatis" or "multilayer stent" for relevant articles from January 2008 to September 2012. Relevant websites (provided by Cardiatis) were also involved in the review process.</p><p><b>STUDY SELECTION</b>Well-controlled, relatively large-scale, retrospective studies as well as meaningful individual cases were all selected as materials.</p><p><b>RESULTS</b>A total of 23 articles were involved in this review. The newly introduced Cardiatis multilayer stent aims at creating an active flow-modulating barrier between normal blood flow and aneurismal sac, which can induce thrombosis within aneurismal sac and preserve collateral circulation at the same time. Currently, it has been applied for complicated aneurysms located in different segments of the arterial system.</p><p><b>CONCLUSION</b>This new concept of multilayer uncovered stent offers a promising alterative in the treatment of arterial aneurysms. However, a further large-scale clinical and hemodynamic study is required to evaluate the long-term effects.</p>

The experimental study of monitoring gene-based therapy with the binding of diglycylcysteine binding motifs and 99Tcm-glucoheptonate / 中华核医学杂志

Objective To evaluate the feasibility of monitoring the gene expression of VEGF165 via the diglycylcysteine (GGC) reporter gene system by reporter probe of 99Tcm-GH. Methods DNA fragments encoding GGC binding motifs were prepared by PCR and positioned at the C end of VEGF165 gene after the linearization of pcDNA3-VEGF165 plasmid. A replication-defective adenovirus vector Ad5-VEGF165GGC motif-internal ribosomal entry site(IRES) -enhanced green fluorescent protein (EGFP) (Ad5-VIE)was constructed, with a cytomegalovirus (CMV) early promoter driving the expression of VEGF165 gene,GGC motif and EGFP, under the aid of an IRFS. A replication-defective adenovirus carrying the Ad5-EGFP was used as the control. Mensenchymal stem cells (MSC) were infected with the recombinant adenovirus at a multiplicity of infection (MOI) from 0 to 100 infectious units (0,10,25,50,100). The cellular uptake of 99Tcm-GH in infected MSC were then studied at 30, 60, 90 and 120 min. VEGF165 was detected by quantitative reverse transcriptase real-time PCR (RT-PCR), Western-blot, and immunohistochemisty. EGFP was observed by RT-PCR and fluorescence microscopy. The correlation analysis was studied between the cellular uptake of 99Tcm-GH and the expression of VEGF165. SPSS 13.0 was applied for statistical analysis. Independent samples t-test, q-test and Pearson correlation coefficient were used. Results After infected with different viral titer of Ad-VIE, the cellular uptake of 99Tcm-GH increased with the increasing virus titer(r2 =0.86, P ＜0.05), with the peak rate (7.94 ±0.75) % at MOI = 100. In time-dependent uptake study, the cellular uptake rates increased rapidly with the time extension, and the highest uptake occurred at 120 min with the peak uptake rate (7.72 ±0.22)%. The uptake rates of 99Tcm-GH in Ad5-VIE-infected cells were significantly higher than those of Ad5 -EGFP-transfected cells at all time points (t = 15.10- 54.92, all P ＜0.05). The VEGF165 and EGFP mRNA levels increased with increasing virus titer, and the VEGF165 mRNA correlated well with the EGFP mRNA(r2 = 0. 99, P ＜ 0.05). After infected with different MOI of Ad5-VIE, good relationship was found between the cellular uptake of 99Tcm-GH and the expression of VEGF165protein in MSC(r2 =0.90, P ＜0.05). Inmunohistochemisty showed VEGF165 protein expressed obviously at Ad5-VIE-infected MSC, and the EGFP was observed by fluorescence microscopy. Conclusions The cellular uptake of 99Tcm-GH in Ad5-VIE-infected MSC are well correlated with the expression of VEGF165 in vitro. The expression of therapeutic gene VEGF165 can be monitored by the GGC peptide expression.

Study of rNIS as a reporter gene monitoring rBMSC transplanted to rat myocardium / 中华核医学杂志

Objective To investigate the feasibility of rat sodium/iodide symporter (rNIS) as a reporter gene monitoring rat bone marrow mesenchymal cells (rBMSC) transplanted to rat myocardium in vivo.Methods Recombinated adenovirus vector was constructed by rNIS/enhanced green fluorescence protein (EGFP) (Ad-rNIS/EGFP).rBMSC transfected by Ad-rNIS/EGFP were studied using fluorescence microscope.Fifteen rats were transplanted with rBMSC and randomly divided into three groups:rNIS group (with rNIS transfection), blocked group (with rNIS transfection) by oral intake of perchloric sodium before planar imaging(GE Millennium MPR SPECT), and control group (without rNIS transfection).All rats underwent 99Tcm-pertechnetate planar imaging.The biological distribution of 99Tcm-pertechnetate was studied.The expressions of rNIS gene and protein in myocardium were measured by real time polymerase chain reaction (PCR) and western blot, respectively.The expressions of CD29, CD44, CD90, CD11b, CD34 and CD45 were measured by immunohistochemistry.Results rBMSC transfected by Ad-rNIS/EGFP showed EGFP expression under fluorescence microscope.The transplanted rat myocardium could be visualized on 99Tcm-pertechnetate planar imaging in rNIS group.The relative uptake ratio( Rheart/Rhmb, RUR) was 6.7 ±0.4.RUR in control group (3.0 ±0.2) was lower than that in rNIS group (t =2.78, P=0.03).The percentage injection dose per gram of tissue (% ID/g) of the transplanted myocardium was 60.2 ± 20.8 in rNIS group,which was higher than that (2.5 ± 0.4) % ID/g of control group ( t = 7.13, P＜0.001 ).rNIS gene and protein were highly expressed in transplanted myocardium in rNIS group but less expressed in control group.The expressions of CD29, CD44 and CD90 were positive, CD45 and CD45 negative CD11b mildly positive in the myocardium transplanted with infective rBMSC.Conclusion rNIS can efficiently monitor rBMSC transplanted to rat myocardium.

~(18)F-FDG PET/CT for the evaluation of pathological changes of the VX2 rabbit tumors after treatment of Ar-He knife / 中华核医学杂志

Objective To study the correlation of ~(18)F-fluorodeoxyglucose (FDG) PET/CT with pathological changes of the VX2 rabbit tumors after treatment of Ar-He knife,and to explore the evolution of the Ar-He knife curative effect for VX2 rabbit tumors.Methods Thirty-six Japanese white rabbits had successfully been implanted with VX2 tumors in thighs.Four weeks later,the rabbits with VX2 tumors were imaged with FDG PET/CT before they were treated with Ar-He cryoablation.The rabbits were evenly and randomly divided into 6 groups (6 rabbits in each group) and imaged with FDG PET/CT respectively on the first day,third day,seventh day,fourteenth day,thirtieth day and sixtieth day after cryoablation.The rabbits in each group were sacriftced after post-treatment FDG PET/CT imaging for pathology and immunohistochemistry studies.The standardized uptake value (SUV) of tumor regions were calculated and compared with pathology and immunohistochemistry findings in the cryoablative area in each group.Paired-samples t-test and bivariate correlation analysis were evaluated by statistical software SPSS 16.0.Results After ArHe cryoablation,pathological changes of "necrosis-inflammatory response→organization" were found.On CT imaging,the tumors enlarged during 3-14 d after treatment and then shrank gradually.On FDG PET imaging,the maximum SUV (SUV_(max)) dropped dramatically on the first day after the operation(from 2.54±1.12 to 0.67±0.12),and increased slightly on the third day (1.71±0.82),and then continually dropped to 0.51±0.32 (60 d afterthe operation).The differences of SUV_(max) between pre-and after cryoablationin each stage were significant,respectively (t=5.471,8.716,11.388,5.713,7.144 and 7.213,all P＜0.05).The size and SUV_(max) of the targeting area did not correlate with each other(r=0.259,P=0.675).The change of the MVD closely correlated with SUV_(max)(r=0.865,P=0.032).Conclusion FDG PET/CT can reveal the pathological change of tumor tissue after Ar-He cryoablation therapy and therefore may be a potential tool for evaluating the curative effect of this treatment modality.

Treatment on post-operational complications of aortic endovascular grafting exclusion / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the post-operative complications of aortic endovascular grafting exclusion (EVGE) and its reasons and treatments.</p><p><b>METHODS</b>Clinical data of 82 cases received aortic endovascular grafting exclusion from January 2002 to October 2008 were retrospectively analyzed. Seventy-one cases were male and 11 cases were female with the age of 33 to 78 years and the average age of 49.2 years. There were 66 cases of thoracic aortic dissecting aneurysms and 16 cases of abdominal aortic aneurysm. The effect, post-operational complications and its treatment were investigated.</p><p><b>RESULTS</b>There were 90.1% patients had been followed up with the time of 3 to 78 months with technical success of 90.3%, clinical success of 94.1%, peri-operational mortality of 2.4%, total mortality of 6.1% and mortality associated with EVGE of 2.4%. Twenty-one cases underwent complications including type I endoleak (13 cases), abdominal aortoduodenal fistula (1 case), narrow true lumen (2 cases), reverse Stanford A dissection (2 cases), post EVGE syndrome (12 cases), delayed healing of inguinal incision (5 cases), constipation (3 cases), cerebral infarction (1 case). No paraplegia, left subclavian artery ischemia, contrast media associated nephrosis, ischemic colitis, ischemic neurologic injury, and artery embolism occurred. Post operation 4 cases had the second intervention including 2 type I endoleak and 2 narrow true lumen.</p><p><b>CONCLUSIONS</b>The technique-related complications still hinder the long-term effect of EVGE. It needs to be further investigated on technique improvement and treatment standardization.</p>

Myocardial single photon emission tomography imaging of reporter gene expression in rabbits / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the feasibility of single photon emission computed tomography (SPECT) detection of heart reporter gene expression and observed the optimal transfecting titer and imaging time by using herpes simplex virus 1-thymidine kinase (HSV1-tk) as reporter gene and 131I-2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodouracil (131I-FIAU) as reporter probe in rabbit myocardium.</p><p><b>METHODS</b>The recombinant Ad-tk carrying HSV1-tk gene and adenovirus (Ad) as vector was constructed and intramyocardially injected to rabbits at various concentrations (1 x 10(9) pfu, 5 x 10(8) pfu, 1 x 10(8) pfu, 5 x 10(7) pfu, 1 x 10(7) pfu). Two days later, rabbits were injected with 600 microCi 131I-FIAU in ear-margin vein and then underwent SPECT myocardium imaging for detection of HSV1-tk expression at 6 h, 24 h, 48 h and 72 h after injection, rabbits with 1 x 10(9) pfu Ad-tk injection were imaged at 96 h and 120 h. Rabbits were sacrificed after imaging and the total myocardial 131I-FIAU accumulation was quantified in percent of injected dose per gram myocardium (% ID/g). The myocardial Ad-tk expression was determined with RT-PCR.</p><p><b>RESULTS</b>Reporter gene was detected by SPECT imaging in the injection site while not detected in the control myocardium and site remote from injection. RT-PCR results also evidenced HSV1-tk express in the injection site. The SPECT target/nontarget ratio was correlated with ex vivo gamma-counting (r2 = 0.933, P<0.01) and expression of HSV1-tk (r2 = 0.877, P<0.01). Myocardial accumulation could be identified at viral titers as low as 1 x 10(7) pfu by SPECT imaging.</p><p><b>CONCLUSION</b>The cardiac SPECT reporter gene imaging with HSV1-tk as reporter gene and 131I-FIAU as reporter probe is feasible.</p>

Autoradiography reporter gene (Ad5-tk carrying HSV1-tk gene) expression imaging in rat myocardium / 中华心血管病杂志

<p><b>OBJECTIVE</b>Radionuclide imaging of reporter gene expression holds promise for noninvasive monitoring of gene therapy. Herpes simplex virus 1-thymidine kinase (HSV1-tk) has been successfully applied to the tumor tissue.We explored the feasibility of the expression imaging of HSV1-tk reporter gene in rat myocardium by using SPECT reporter probe (131)I-2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodouracil ((131)I-FIAU) and autoradiography (ARG).</p><p><b>METHODS</b>The recombinant Ad5-tk carrying HSV1-tk gene and adenovirus (Ad5-null) as vector were constructed and intramyocardially injected into SD rats. Experiment was grouped for different aims as follows: (1) Influence of time on the imaging after transfection reporter gene: rats were injected with (131)I-FIAU at day 1, 2, 3, 5 and 7 after transfection of 1 x 10(8)pfu Ad5-tk; (2) Influence of various titers on the imaging: rats underwent intramyocardial injection with various titers of Ad5-tk (5 x 10(8), 1 x 10(8), 5 x 10(7), 1 x 10(7)pfu). After 2 days, rats were injected with (131)I-FIAU in tail vein. Equal volume Ad-nulls was intramyocardially injected to control rats. Rats were killed 24 h after injection of (131)I-FIAU and the hearts were rapidly dissected for gamma counts measurement. The total myocardial (131)I-FIAU accumulation was quantified in percent of injected dose per gram myocardium (%ID/g). The myocardial reporter gene expression was semi-quantitatively determined by ARG and RT-PCR.</p><p><b>RESULTS</b>ARG and RT-PCR showed that the local expression of reporter gene increased in proportion with increasing titer and decreased in proportion with time post injection. The semi-quantitative assay showed there were significant correlations among %ID/g, RT-PCR and ARG: r(2) = 0.963, P < 0.05 for RT-PCR and ARG; r(2) = 0.996, P < 0.01 for %ID/g and ARG in rats received various reporter gene titers at identical time point post injection; r(2) = 0.950, P < 0.05 for RT-PCR and ARG; r(2) = 0.980, P < 0.01 for %ID/g and ARG for rats received identical reporter gene titer on various time points post injection.</p><p><b>CONCLUSIONS</b>The present study showed that cardiac reporter gene imaging with HSV1-tk as reporter gene and (131)I-FIAU as reporter probe was feasible in rats. The optimal Ad5-tk titer is 1 x 10(8) pfu and the optimal imaging time is 24 h to 48 h post gene transfer. HSV1-tk/FIAU may be used for the noninvasive monitoring of cardiac gene therapy.</p>

Feasibility of apoptosis-imaging agent 99mTc-HYNIC-annexin V in early assessment of chemotherapeutic effect on tumor models / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate if 99mTc-HYNIC-annexin V may be used to detect the early chemotherapeutic effect and to determine the best timing for detecting apoptosis in vivo.</p><p><b>METHODS</b>Annexin V was labeled with 99mTc using HYNIC as a bifunctional agent. Normal Kunming mice received inoculation of Ehrlich ascites cells into the right upper limb. After the tumor reached 1 cm in diameter, the mice were randomly divided into saline treatment group as control and cyclophosphamide (150 mg/kg injected intraperitoneally) treatment group. 99mTc-HYNIC-annexin V was injected intravenously at 1 h and 24 h after treatment. Region of interest technique (ROI) from the SPECT images taken at different time was used to get the ratio of tumor/limb in each group. TUNEL staining was used to detect apoptotic cells and the rates of positive stained cells were calculated.</p><p><b>RESULTS</b>After treatment with saline, only little amount of the radiolabeled tracer could be seen in the tumor and showed weak image of the tumor. But after 24 h of treatment with cyclophosphamide, clear image on the tumor could be seen. 24 h after the treatment of cyclophosphamide, the ratio of tumor/limb was (6.27 +/- 0.24) which was much higher than that at 24 h after treatment with saline (2.36 +/- 0.18) and that at 1 h after cyclophosphamide treatment (4.00 +/- 0.38). At 24 h after cyclophosphamide treatment, TUNEL staining showed a significantly higher rate of apoptotic cells in the mice.</p><p><b>CONCLUSION</b>99mTc-HYNIC-annexin V can be used as an apoptosis-imaging agent to detect and evaluate the early curative effect after chemotherapy. The effective detection of apoptotic response in tumor with 99mTc-HYNIC-annexin V requires a 24 h interval after chemotherapy. SPECT images can be obtained at 60 min after injection of the imaging agent. It suggests that 99mTc-HYNIC-annexin V may become a promising agent for apoptosis-imaging in clinical application.</p>

Targeted radionuclide therapy for patients with metastatic medullary thyroid carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the effect of 90Y-DOTATOC and 131I-MIBG in treatment of metastatic medullary thyroid carcinoma (MTC).</p><p><b>METHODS</b>Twelve histologically confirmed patients with metastatic MTC were included. All patients underwent both 111In-DTPA-octreotide imaging and 131I/ 123I-meta-iodobenzylguanidine (MIBG) imaging. According to the results of the combined imaging, positive patients were selected to be treated with 90Y-DOTA-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) or 131I-MIBG, respectively. The therapeutic procedures of targeted internal radiation were performed with 3.33 GBq 90Y-DOTATOC at 6-week intervals, or 11.1 GBq 131I-MIBG with a minimum interval of three months.</p><p><b>RESULTS</b>The imaging procedure was positive in all 12 patients: 111In-DTPA-octreotide imaging in eight patients, 131I/ 123I-MIBG imaging in six patients. According to the results of combined imaging, we identified four patients to be treated with 90Y-DOTATOC, and five patients with 131 I-MIBG. After three to five sessions of treatment, three patients with partial remission and six with stable disease were observed. The effective rate was 3/9 (33.3%) and the overall tumor response rate was 9/9 (100%). No relevant toxicity was observed.</p><p><b>CONCLUSION</b>The combined imaging technique can be used to identify patients for effective radionuclide treatment. The treatment with 90Y-DOTATOC or 131I-MIBG is well tolerated and may improve the fate of patients with metastatic MTC.</p>

Experimental study of transferrin receptor molecular imaging in human hepatocellular carcinoma transplanted in nude mice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the feasibility of (99m)Tc-transferrin ((99m)Tc-Tf) as an transferrin receptor imaging agent in nude mice bearing human hepatoma SMMC-7721 tumor.</p><p><b>METHODS</b>Biodistribution of (99m)Tc-Tf in Balb/c mice was assayed, and transferrin receptor imaging in Balb/c nu/nu nude mice bearing human hepatocellular carcinoma SMMC-7721 xenografts was carried out, with or without inhibition of transferrin receptor with unlabeled transferrin. The receptor radioligand binding assay with (125)I-transferrin as ligand was established, and the number of receptors per cell and the K(d) were worked out.</p><p><b>RESULTS</b>(99m)Tc-Tf was mainly distributed in the liver, blood and kidneys. At 18 h post injection, the ratios of tumor/blood, tumor/liver and tumor/muscle were 24.2, 1.7 and 35.5, respectively. The ratio of tumor uptake at 18 h without unlabeled transferrin pretreatment to that with pretreatment was 16.3. The number of receptors per cell was 2.4 x 10(5) and the K(d) was found to be 4.46 nmol/L.</p><p><b>CONCLUSION</b>All those results indicate that (99m)Tc-Tf is specifically localized in tumor lesions of nude mice. (99m)Tc-Tf may be useful in detection of hepatocellular carcinoma.</p>

An imaging study using laminin peptide 99mTc-YIGSR in mice bearing Ehrlich ascites tumour / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The YIGSR is a pentapeptide, from the laminin-1 of the beta1 chain, which can mediate cell adhesion and bind the 67 kD laminin receptor. The purpose is to evaluate the usefulness of (99m)Tc-YIGSR, a novel tumour radiotracer, in the receptor imaging of Ehrlich ascites tumour.</p><p><b>METHODS</b>Using S-acetly-NH3-MAG3 as chelate, YIGSR, a pentapeptide from laminin, was tagged with (99m)Tc. (99m)Tc-YIGSR was detected in the tumour group bearing Ehrlich ascites tumour and blocked group. Tumour, normal, inflammatory and blocked groups were imaged.</p><p><b>RESULTS</b>Through reverse phase Sep-Pak C18 chromatogram, it was revealed that YIGSR could conjugate with S-acetly-NH3-MAG3, and be radiolabelled at room temperature and neutral pH with a radiolabelling yield of 62%, and of 4% without chelate. (99m)Tc-YIGSR was rapidly cleared from kidney, then liver. The imaging findings showed tumour tissue accumulated initial radioactivity at fifteen minutes after injection in the tumour group, and the uptake increased to peak at three hours with a tumour/muscle ratio (T/M) of 11.36, then cleared slowly to a T/M of 7.50 at eight hours. The tumour uptake of radiotracer in blocked group was significantly lower with T/M of 4.61 at three hours and 0.89 at eight hours. The T/M was only 3.72 at three hours and 1.29 at eight hours after injection in inflammatory group. Compared with inflammatory group and control obstructive group, the ratio of T/M in tumour group was significantly different (P < 0.001).</p><p><b>CONCLUSIONS</b>Using S-acetly-NH3-MAG3, we radiolabelled YIGSR with (99m)Tc. (99m)Tc-YIGSR possesses many merits of tumour imaging: rapid visualization, high sensitivity and specificity, and satisfactory target/nontarget ratio. Our data suggest (99m)Tc-YIGSR is a promising tumour radiotracer.</p>

Diagnosis and surgical treatment of thoracictuberculosis / 中国基层医药

Objective To summarize the experience of the therapy and diagnosis of thoracictuberculosis. Methods Diagnosis and operation of 163 cases of thoracictuberculosis were analyzed.Results 163 cases of thoracic- tuberculosis were treated with focuspurge upon two weeks' anti-tuberculosis treatment.153 cases were cured upon one operation.10 cases suffered incision delayed healing and there were no recurrence cases.Conclusion Thoraeictu- berculosis was treated with focuspurge upon two weeks anti-tuberculosis treatment before operation.Complete purge of focus and postoperative compression band and residual cavity filled with music flap were important measures to prevent incision delayed healing and recurrence.