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Retinoic acid (RA) analogs have been used in the treatment of a variety of cancers; however, their application is limited due to serious therapy-related sequelae. In the present study, the effects of a novel RA analog, 4-amino-2-trifluoromethyl-phenyl retinate (ATPR), on the growth of gastric cancer cells were evaluated. Three gastric cancer cell lines, AGS, MKN-74 and SC-M1, were treated with either all‑trans retinoic acid (ATRA) or ATPR, and their growth and distribution in different cell cycle phases were assessed using an MTT assay and propidium iodide (PI) staining followed by flow cytometry. The binding affinity of ATPR to the retinoic acid receptors, retinoic acid receptor-α (RAR-α) and retinoid X receptor-α (RXR-α), was determined using ligand-binding assays. Activator protein-1 (AP-1) activity was measured using a luciferase reporter assay. Western blot analysis was used to determine cyclin E, Bcl-2 and Bax protein expression. ATPR preferentially bound RXR-α (0.04 nM) as compared with RAR-α (20.96 nM). Although both ATRA and ATPR inhibited the growth of AGS, MKN-74 and SC-M1 cells in a dose-dependent manner, a significantly greater inhibitory effect was observed with treatment with 5 and 500 µM ATPR for 3 days (P

Objectives The authors investigate whether the combination of anti-CD34 antibody with DES is win-win cooperation. Background DES may reduce the risk of restenosis compared to bare-metal stents (BMS), but they were found to inhibit the healing process of intima. Methods Fifteen BMS, 17 DES, and 16 combined anti-CD34 antibody and DES were randomly implanted in the coronary arteries of 22 minipigs. Ten minipigs were followed up to 2 weeks. The stenting coronary segments were examined by histological examination and scanning electron microscopy after in vivo coronary angiography and intracoronary optical coherence tomography (OCT) examinations. The other 12 minipigs were followed up to 3 months. Coronary angiography and intracoronary OCT examination were performed in vivo and histological examination was performed on the stenting coronary segments. Results After 2 weeks, the neointimal covering level of the DES was lower than that in BMS, but the covering level of the combined stents was even better than the BMS. After 3 months, neointimal hyperplasia was significant in the BMS, but not in the other two types of stents. The in-stent late lumen loss of the combined stents even showed a decreasing tendency when compared with the DES. Conclusion The combination of anti-CD34 antibody and DES can not only well offset the short-term inhibitory effect on re-endothelialization but also slightly enhance the long-term antiproliferative effect.

Standard endovascular repair of iliac/aortoiliac pathologies can lead to complications, such as buttock claudication, colon ischemia and erectile dysfunction. Branch grafts have been developed but require at least 6 weeks for customization and are not currently available in China; they are also quite expensive. To our knowledge, modified fenestrated stent grafts (MFSGs) are a safe and effective alternative for treating patients with juxtarenal aneurysms. Most MFSGs are used for the preservation of renal and left subclavian arteries. Few cases of MFSGs have been reported in the treatment of iliac pathologies. The use of an MFSG is decided on a case-by-case basis. This report presents our first clinical use of an MFSG for preservation of the internal iliac artery.

Drug-eluting stents have shown an impressive reduction of in-stent restenosis for many years. However, stent thrombosis due to incomplete/late endothelialization has raised major safety concerns. To overcome these problems, we developed for the first time a polymer-free sirolimus-eluting antibody-coated stent (PFSEACS) by combining polymer free and endothelial progenitor cell-capture pro-healing approaches. In the first phase, the stents were prepared by loading sirolimus on the porous outer stent surface and directly fixing the anti-CD34 antibodies without any medium carriers on the blood contacting surface. The dose and elution of sirolimus, the amount and stability of anti-CD34 antibody immobilization, and the rate of CD34+ cell capture were evaluated. In the second phase, the stents were validated in an animal model of coronary arteries in pigs. The stent was observed to start collecting endothelial progenitor cells ~2 h after stent implantation and exhibited greatly enhanced endothelialization while maintaining an excellent anti-restenosis activity comparable to the polymer-free sirolimus-eluting stents. Overall, both in vitro and in vivo evaluations indicated that novel PFSEACSs exhibited facilitated endothelialization with excellent anti-restenosis activity and thus should merit further clinical studies.

To investigate the impact of the stents coated with sirolimus and anti-CD34 antibody on the short-term re-endothelialization and the long-term restenosis in Chinese Minipigs.Three different types of stents [bare-metal stent (BMS), sirolimus-eluting stent (SES) and anti-CD34 antibody and sirolimus-coated stent (ASES)] were randomly implanted in the coronary arteries of 22 Chinese Minipigs. At two weeks after stenting, coronary angiography and optical coherence tomography (OCT) were performed in 10 experimental animals. At three months after stenting, coronary angiography and OCT were performed in the remaining 12 experimental animals. Histopathologic examination was performed on the coronary artery segments containing stent after the animals were executed.(1) No in-stent thrombosis and parietal thrombus were found by coronary angiography, OCT and histopathologic examination at two weeks post stenting. OCT analysis showed that the covered ratio of stent struts by neointima in ASES group was higher than in SES group [(55.56 ± 35.27)% vs. (41.82 ± 23.28)%, P0.05]. The mean thickness of neointima in ASES group was significantly higher than in SES group [(89.0 ± 5.0) µm vs. (32.0 ± 4.9) µm, P0.01] and BMS group [(89.0 ± 5.0) µm vs. (44.0 ± 7.2) µm, P0.01]. Histopathologic and scanning electron microscopy examinations demonstrated that the covering level and quality of stent struts by neointima in BMS and ASES group were both better than in SES group. (2) At three months follow-up, quantitative coronary angiography analysis found that late in-stent lumen loss in ASES group was significantly lower than in BMS group [(0.18 ± 0.06) mm vs.(0.35 ± 0.06) mm, P0.05]. OCT analysis showed that the percent neointimal hyperplasia in ASES and SES group was significantly lower than in BMS group [(34.75 ± 2.64)% and (35.63 ± 2.07)% vs. (48.28 ± 3.25)%, both P0.01]. Histopathologic analysis demonstrated that the percent areal restenosis of ASES and SES group were both significantly lower than that of BMS group [(28.65 ± 5.64)% and (29.33 ± 6.07)% vs. (46.18 ± 8.25)%, both P0.05].The stents coated with anti-CD34 antibody and sirolimus can attenuate the inhibitory effect of sirolimus on the re-endothelialization at two weeks after stenting and the anti-hyperplasia effect of sirolimus at three months after stenting.

Adenosine phosphate-mediated platelet aggregation is a prognostic factor for major adverse cardiac events in patients who have undergone selective percutaneous coronary interventions. This study aimed to assess whether an adjusted loading dose of clopidogrel could more effectively inhibit platelet aggregation in patients undergoing selected percutaneous coronary intervention.A total of 205 patients undergoing selected percutaneous coronary intervention were enrolled in this multicenter, prospective, randomized study. Patients receiving domestic clopidogrel (n = 104) served as the Talcom (Taijia) group; others (n = 101) received Plavix, the Plavix group. Patients received up to 3 additional 300-mg loading doses of clopidogrel to decrease the adenosine phosphate-mediated platelet aggregation index by more than 50% (the primary endpoint) compared with the baseline. The secondary endpoint was major adverse cardiovascular events at 12 months.Compared with the rational loading dosage, the tailored loading dosage better inhibited platelet aggregation based on a50% decrease in adenosine phosphate-mediated platelet aggregation (rational loading dosage vs. tailored loading dosage, 48% vs. 73%, P = 0.028). There was no significant difference in the eligible index between the Talcom and Plavix groups (47% vs. 49% at 300 mg; 62% vs. 59% at 600 mg; 74% vs. 72% at 900 mg; P0.05) based on a standard adenosine diphosphate-mediated platelet aggregation decrease of50%. After 12 months of follow-up, there were no significant differences in major adverse cardiac events (2.5% vs. 2.9%, P = 5.43). No acute or subacute stent thrombosis events occurred.An adjusted loading dose of clopidogrel could have significant effects on antiplatelet aggregation compared with a rational dose, decreasing 1-year major adverse cardiac events in patients undergoing percutaneous coronary interventions based on adenosine phosphate-mediated platelet aggregation with no increase in bleeding.

To analyze the clinical data, surgical strategies and results from the patients with hilar cholangiocarcinoma (HCCA), and to explore the anatomic factors related to the radical resection.The data from 52 patients with HCCA who underwent radical resection between January 1984 to December 2008 were investigated retrospectively, which included clinical diagnosis, Bismuth-Corlette classification, pathologic features, surgical procedures and follow-up results.According to the Bismuth-Corlette classification, 5, 12, 6, 16 and 13 patients belonged to type I, II, IIIa, IIIb and IV respectively. There were 24 cases underwent combined hepatic lobectomy. The 1-, 3- and 5-year survival rates were 78.8%, 36.4% and 12.1% respectively. Postoperative complications rate was 30.8% with the 3.8% mortality rate. The frequency of surgical complications was significantly higher in patients with higher level of serum total bilirubin (340 micromol/L) than that in patients with a relatively lower one (170 micromol/L) before operation (P0.05).Some anatomical factors should be considered during the radical resection of hilar cholangiocarcinoma, especially evaluation of potential hepatectomy, resection of caudate lobe, hepatic artery resection and/or reconstruction. The prognosis of the patients underwent R(0) radial resection could be significantly improved.

To identify the potential predictors of restenosis after bare mental stent (BMS) deployment in diabetic patients in Chinese diabetic patients.We retrospectively analyzed all patients implanted with BMS (n = 1126 with 2376 lesions) in our department from 2002 to 2004. The multivariate logistic regression analysis was made to compare the clinical and angiographic characteristics between diabetic patients with and without restenosis. Restenosis was defined asor = 50% diameter stenosis within the stent and 5 mm in adjacent.The 6-month follow-up angiograms were available in 889 out of 1126 patients (78.9%) and 151 out of 889 patients (17%) were diabetic patients. Restenosis rate in nondiabetic patients group was 21.2% and 35.9% in diabetic patients (P0.001). The predictors of restenosis in diabetics were reference vessel diameter (or = 3.0 mm), length of lesion (15 mm) and insulin use (P0.05). The restenosis predicting model showed that reference vessel caliber was the paramount predictor for restenosis in diabetic patients.Restenosis rate post BMS implantation is significantly higher in diabetic patients compared to non-diabetic patients. Vessel caliber, lesion length and insulin use are predictors of restenosis in diabetic patients. Diabetic patients with reference vessel diameter of3.0 mm combined with lesion length15 mm and non-diabetic patients with lesion length15 mm regardless of the vessel caliber could be treated with BMS since the predicted restenosis rate is lower than 15% in these patients, otherwise DES would be a better choice.